{
    "Contributors": [
        "Jalansh Munshi"
    ],
    "Source": [
        "PubMedQA"
    ],
    "URL": [
        "https://huggingface.co/datasets/pubmed_qa"
    ],
    "Categories": [
        "Text Completion"
    ],
    "Reasoning": [],
    "Definition": [
        "Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage."
    ],
    "Input_language": [
        "English"
    ],
    "Output_language": [
        "English"
    ],
    "Instruction_language": [
        "English"
    ],
    "Domains": [
        "Academical Papers"
    ],
    "Positive Examples": [
        {
            "input": "Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 \u00b1 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).",
            "output": "Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?",
            "explanation": "The question is based on the following sentences from the passage (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) They were also associated with increased blood eosinophilia"
        },
        {
            "input": "Phosphatidylethanolamine N-methyltransferase (PEMT), a liver enriched enzyme, is responsible for approximately one third of hepatic phosphatidylcholine biosynthesis. When fed a high-fat diet (HFD), Pemt(-/-) mice are protected from HF-induced obesity; however, they develop steatohepatitis. The vagus nerve relays signals between liver and brain that regulate peripheral adiposity and pancreas function. Here we explore a possible role of the hepatic branch of the vagus nerve in the development of diet induced obesity and steatohepatitis in Pemt(-/-) mice. 8-week old Pemt(-/-) and Pemt(+/+) mice were subjected to hepatic vagotomy (HV) or capsaicin treatment, which selectively disrupts afferent nerves, and were compared to sham-operated or vehicle-treatment, respectively. After surgery, mice were fed a HFD for 10 weeks. HV abolished the protection against the HFD-induced obesity and glucose intolerance in Pemt(-/-) mice. HV normalized phospholipid content and prevented steatohepatitis in Pemt(-/-) mice. Moreover, HV increased the hepatic anti-inflammatory cytokine interleukin-10, reduced chemokine monocyte chemotactic protein-1 and the ER stress marker C/EBP homologous protein. Furthermore, HV normalized the expression of mitochondrial electron transport chain proteins and of proteins involved in fatty acid synthesis, acetyl-CoA carboxylase and fatty acid synthase in Pemt(-/-) mice. However, disruption of the hepatic afferent vagus nerve by capsaicin failed to reverse either the protection against the HFD-induced obesity or the development of HF-induced steatohepatitis in Pemt(-/-) mice.",
            "output": "Does vagus nerve contribute to the development of steatohepatitis and obesity in phosphatidylethanolamine N-methyltransferase deficient mice?",
            "explanation": "The question is based on the following sentences from the passage (i) Phosphatidylethanolamine N-methyltransferase (PEMT), (ii) vagus nerve in the development of diet induced obesity and steatohepatitis in Pemt(-/-) mice."
        },
        {
            "input": "Psammaplin A (PsA) is a natural product isolated from marine sponges, which has been demonstrated to have anticancer activity against several human cancer cell lines via the induction of cell cycle arrest and apoptosis. New drugs that are less toxic and more effective against multidrug-resistant cancers are urgently needed. We tested cell proliferation, cell cycle progression and autophagic cell death pathway in doxorubicin-resistant MCF-7 (MCF-7/adr) human breast cancer cells. The potency of PsA was further determined using an in vivo xenograft model.",
            "output": "Does psammaplin A induce Sirtuin 1-dependent autophagic cell death in doxorubicin-resistant MCF-7/adr human breast cancer cells and xenografts?",
            "explanation": "The question is based on the following sentences from the passage (i) Psammaplin A (PsA) is a natural product, (ii) We tested cell proliferation, cell cycle progression and autophagic cell death pathway in doxorubicin-resistant MCF-7 (MCF-7/adr) human breast cancer cells, (iii) potency of PsA was further determined using an in vivo xenograft model"
        }
    ],
    "Negative Examples": [
        {
            "input": "This study examined links between DNA methylation and birth weight centile (BWC), and explored the impact of genetic variation. Using HumanMethylation450 arrays, we examined candidate gene-associated CpGs in cord blood from newborns with low (<15th centile), medium (40-60th centile) and high (>85th centile) BWC (n = 12). Candidates were examined in an investigation cohort (n = 110) using pyrosequencing and genotyping for putative methylation-associated polymorphisms performed using standard PCR. Array analysis identified 314 candidate genes associated with BWC extremes, four of which showed \u2265 4 BWC-linked CpGs. Of these, PM20D1 and MI886 suggested genetically determined methylation levels. However, methylation at three CpGs in FGFR2 remained significantly associated with high BWC (p = 0.004-0.027).",
            "output": "Is FGFR2 associated with genetic mutation?",
            "explanation": "The input passage does not say anything regarding FGFR2 being associated with genetic mutation. Hence, this question is a bad example."
        },
        {
            "input": "Tumor microenvironment immunity is associated with breast cancer outcome. A high lymphocytic infiltration has been associated with response to neoadjuvant chemotherapy, but the contribution to response and prognosis of immune cell subpopulations profiles in both pre-treated and post-treatment residual tumor is still unclear. We analyzed pre- and post-treatment tumor-infiltrating immune cells (CD3, CD4, CD8, CD20, CD68, Foxp3) by immunohistochemistry in a series of 121 breast cancer patients homogeneously treated with neoadjuvant chemotherapy. Immune cell profiles were analyzed and correlated with response and survival. We identified three tumor-infiltrating immune cell profiles, which were able to predict pathological complete response (pCR) to neoadjuvant chemotherapy (cluster B: 58%, versus clusters A and C: 7%). A higher infiltration by CD4 lymphocytes was the main factor explaining the occurrence of pCR, and this association was validated in six public genomic datasets. A higher chemotherapy effect on lymphocytic infiltration, including an inversion of CD4/CD8 ratio, was associated with pCR and with better prognosis. Analysis of the immune infiltrate in post-chemotherapy residual tumor identified a profile (cluster Y), mainly characterized by high CD3 and CD68 infiltration, with a worse disease free survival.",
            "output": "How does chemotherapy cure breast cancer?",
            "explanation": "There is no mention about how chemotherapy can cure breast cancer in the input passage. Hence, this question is a bad example."
        },
        {
            "input": "Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving intertriginous skin. Previous epidemiologic studies have been limited by small sample size. We sought to describe the prevalence and comorbidities of HS in a large patient care database. In this retrospective case-control study, we chart-validated all patients within a hospital database who received at least 1 billing code for HS between 1980 and 2013. Verified cases were matched with controls based on age, gender, and race. Prevalences of a priori selected comorbidities were compared between HS and control groups. A total of 2292 patients at Massachusetts General Hospital received at least 1 code for HS. A total of 1776 cases had a validated diagnosis of HS, yielding a prevalence of 0.08%. In unadjusted analysis, all comorbidities were diagnosed significantly more in HS compared with control including (in rank order of likelihood): smoking, arthropathies, dyslipidemia, polycystic ovarian syndrome, psychiatric disorders, obesity, drug dependence, hypertension, diabetes, thyroid disease, alcohol dependence, and lymphoma (all P < .01).",
            "output": "What is the number of male and female patients from the study at Massachusetts General Hospital?",
            "explanation": "This question is a bad example as there is no mention of the number of male and female patients in the passage."
        }
    ],
    "Instances": [
        {
            "id": "task847-f58634639f1e4d55a4fd83781cd6c178",
            "input": "The interassay variability found in the measurement of testosterone (T) levels warrants the need for laboratories to validate their methods to establish trustworthy cut-off points for diagnosis of male hypogonadism. The aims of this study were to validate measurement of total T (TT) at our laboratory in order to obtain reference ranges for TT, calculated free T (CFT), calculated bioavailable T (CBT), and salivary T (ST) in healthy young men from the Mediterranean region, and to evaluate the potential clinical value of ST by establishing its correlation with serum T.', 'An observational, cross-sectional study with sequential sampling.', 'men aged 18-30 years with body mass index (BMI)<30.', \"chronic diseases, hepatic insufficiency or use of drugs altering circulating T levels. Main outcome measures TT (chemiluminescent immunoassay UniCell DXI 800 [Access T Beckman Coulter]), CFT and CBT (Vermeulen's formula), and ST (radioimmunoassay for serum TT modified for saliva [Coat-A-Count, Siemens]). Descriptive statistical analyses and correlation by Spearman's rho (SPSS 19.0 Inc., Chicago) were used.\", 'One hundred and twenty-one subjects aged 24\u00b13.6 years with BMI 24\u00b12.5 kg/m(2) were enrolled. Hormone study: TT, 19\u00b15.5 nmol/L (reference range [rr.] 9.7-33.3); CFT, 0.38 nmol/L (rr. 0.22-0.79); CBT, 9.7 nmol/L (rr. 4.9-19.2); and ST, 0.35 nmol/L (rr. 0.19-0.68). Correlation between ST and CFT was 0.46.",
            "output": [
                "Does reference range for serum and salivary testosterone in young men of Mediterranean region?"
            ]
        },
        {
            "id": "task847-764e615247e4480386c75d6ed8830166",
            "input": "Secretory phospholipases A2 (sPLA2) initiate the biosynthesis of eicosanoids, are increased in the airways of people with severe asthma, and induce mucin hypersecretion. We used IL-13-transformed, highly enriched goblet cells and differentiated (ciliary cell-enriched) human bronchial epithelial cell culture to evaluate the relative contribution of ciliated and goblet cells to airway sPLA2 generation and response. We wished to determine the primary source(s) of sPLA2 and leukotrienes in human airway epithelial cells.', 'Human bronchial epithelial cells from subjects without lung disease were differentiated to a ciliated-enriched or goblet-enriched cell phenotype. Synthesis of sPLA2, cysteinyl leukotrienes (cysLTs), and airway mucin messenger RNA and protein was measured by real-time-polymerase chain reaction and an enzyme-linked immunosorbent assay, and the localization of mucin and sPLA2 to specific cells types was confirmed by confocal microscopy.', 'sPLA2 group IIa, V, and X messenger RNA expression was increased in ciliated-enriched cells (P < .001) but not in goblet-enriched cells. sPLA2 were secreted from the apical (air) side of ciliated-enriched cells but not goblet-enriched cells (P < .001). Immunostaining of sPLA2 V was strongly positive in ciliated-enriched cells but not in goblet-enriched cells. sPLA2 released cysLTs from goblet-enriched cells but not from ciliated-enriched cells, and this result was greatest with sPLA2 V (P < .05). sPLA2 V increased goblet-enriched cell mucin secretion, which was inhibited by inhibitors of lipoxygenase or cyclooxygenase (P < .02).",
            "output": [
                "Are secretory phospholipases A2 secreted from ciliated cells and increase mucin and eicosanoid secretion from goblet cells?"
            ]
        },
        {
            "id": "task847-417a3a3c75db4629a74ab48cfa8a170b",
            "input": "Hyperglycemia on admission is associated with increased mortality rates in patients with ST-elevation myocardial infarction (STEMI) who are treated with either fibrinolytic therapy (FT) or primary percutaneous coronary intervention (PCI). However, data regarding the relationship between hyperglycemia and the success of FT are lacking. The aim of this study was to investigate the value of admission blood glucose for the prediction of failed reperfusion following FT.', 'This is a retrospective study of 304 STEMI patients who received FT and whose admission glucose levels were recorded. The main outcome measure was ST segment resolution\u226550%. The median (interquartile range [IQR]) blood glucose level in the entire study group was 112 (95-153). In 92 (30.2%) patients, FT was unsuccessful and rescue PCI was performed. Admission glucose (126 [99-192] vs. 110 [94-144] mg/dL, p<0.001), time from symptom onset to FT (180 [120-270] vs. 150 [120-180] min, p=0.009), and maximum ST elevation amplitude (3 [2-7] vs. 3 [2-6] mm, p=0.05) were higher in the failed reperfusion group than in the reperfusion group. Admission hyperglycemia was an independent predictive factor for failed reperfusion (hazard ratio 4.79 [1.80-12.76], p=0.002), along with time from symptom onset to fibrinolysis and anterior wall myocardial infarction.",
            "output": [
                "Is admission hyperglycemia associated with failed reperfusion following fibrinolytic therapy in patients with STEMI : results of a retrospective study?"
            ]
        },
        {
            "id": "task847-3123b6f2a8034c49bd803ea2c116ff68",
            "input": "Publication bias compromises the validity of systematic reviews. This problem can be addressed in part through searching clinical trials registries to identify unpublished studies. This study aims to determine how often systematic reviews published in emergency medicine journals include clinical trials registry searches.', 'We identified all systematic reviews published in the 6 highest-impact emergency medicine journals between January 1 and December 31, 2013. Systematic reviews that assessed the effects of an intervention were further examined to determine whether the authors described searching a clinical trials registry and whether this search identified relevant unpublished studies.', 'Of 191 articles identified through PubMed search, 80 were confirmed to be systematic reviews. Our sample consisted of 41 systematic reviews that assessed a specific intervention. Eight of these 41 (20%) searched a clinical trials registry. For 4 of these 8 reviews, the registry search identified at least 1 relevant unpublished study.",
            "output": [
                "Do systematic Reviews Published in Emergency Medicine Journals Routinely Search Clinical Trials Registries : A Cross-Sectional Analysis?"
            ]
        },
        {
            "id": "task847-cce4ce0fa12b4b6895736258a9d9e657",
            "input": "Obese patients with idiopathic pulmonary fibrosis (IPF) have higher 90-day mortality after lung transplantation. We sought to determine whether body mass index (BMI) differentially modified the effect of transplant procedure type on 90-day mortality in IPF patients.', 'We analyzed data from the Organ Procurement and Transplantation Network (OPTN) for all patients with IPF who were transplanted between 2000 and 2010. Post-transplant survival was examined using Kaplan-Meier estimates. Multivariable logistic regression modeling was used to determine the difference in 90-day survival. The primary variable of interest was the interaction term between body mass index (BMI) and transplant type.', 'A total of 3,389 (58% single-lung transplant [SLT] and 42% bilateral lung transplant [BLT]) subjects were included. Multivariable logistic regression modeling demonstrated a statistically significant interaction between BMI and transplant type (p = 0.047). Patients with a BMI > 30 kg/m(2) who received a BLT are 1.71 times (95% CI [1.03 to 2.85], p = 0.038) more likely to die within 90 days than BLT recipients with a BMI of 18.5 to 30 kg/m(2).",
            "output": [
                "Do obese patients with idiopathic pulmonary fibrosis have a higher 90-day mortality risk with bilateral lung transplantation?"
            ]
        },
        {
            "id": "task847-e8e1ba8bf1ad455e9eafedef02243350",
            "input": "Schizophrenia is recognized as a disorder of the brain and neuronal connectivity. The neural cell adhesion molecule 1 (NCAM1) gene plays a crucial role in regulating neuronal connectivity.', 'We conducted a two-stage association analysis on 17 NCAM1 SNPs in two independent Han Chinese schizophrenia case-control cohorts (discovery sample from Hunan Province: 986 patients and 1040 normal controls; replication sample from Yunnan Province: 564 cases and 547 healthy controls). Allele, genotype and haplotype frequencies were compared between case and control samples. Transcription factor binding site prediction and luciferase reporter assays were employed to assess the potential function of promoter SNPs. We detected developmental changes at the transcriptional level of NCAM1 during neuron differentiation in Macaca mulatta neural progenitor cells (NPC). Serum levels of NCAM1 were measured in 72 cases and 88 controls.', 'A promoter variant, rs2301228, was found to be associated with schizophrenia at the allelic level and was validated in a replication cohort. Luciferase reporter assays demonstrated that risk allele rs2301228-A significantly down-regulated NCAM1 gene transcription compared to the G-allele. Concordantly, schizophrenia patients had a significantly lower level of serum NCAM1 compared to healthy donors. During the NPC neuronal differentiation, NCAM1 mRNA was significantly increased, suggesting a critical role of this gene in neural development.",
            "output": [
                "Does promoter variant rs2301228 on the neural cell adhesion molecule 1 gene confer risk of schizophrenia in Han Chinese?"
            ]
        },
        {
            "id": "task847-2d52feddca5a4411a48718b12c1acf16",
            "input": "Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage.', 'To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity.', '80 patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method.', 'A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean\u00b1SD 82.38\u00b120.46) in comparison to patients without active disease (35.53\u00b17.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I.",
            "output": [
                "Are [ Higher nitric oxide levels associated with disease activity in Egyptian rheumatoid arthritis patients ]?"
            ]
        },
        {
            "id": "task847-a8053b84a9a4474c8cddbc152fa86fff",
            "input": "Activation of B cells is a hallmark of systemic lupus erythematosus (SLE). Syk and TRAF6 are key signaling molecules in B-cell activation through BCR and CD40/TLR, respectively. Nevertheless, whether expression of Syk and TRAF6 is altered in SLE B cells remains unknown.', 'Phosphorylation and/or expression of Syk and TRAF6 were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from SLE patients.', 'Pronounced phosphorylation and expression of Syk were noted in B cells from SLE patients compared with healthy donors. Levels of Syk phosphorylation correlated with the disease activity score. TRAF6 was significantly over-expressed in B cells of SLE patients as compared with healthy donors, and significant correlation of levels of TRAF6 expression and Syk phosphorylation was observed in SLE patients. Levels of TRAF6 expression were more pronounced in CD27+ memory B cells than in CD27-na\u00efve B cells. In vitro treatment of SLE B cells with a Syk inhibitor (BAY61-3606) reduced Syk phosphorylation as well as TRAF6 expression.",
            "output": [
                "Does increased Syk phosphorylation lead to overexpression of TRAF6 in peripheral B cells of patients with systemic lupus erythematosus?"
            ]
        },
        {
            "id": "task847-0f43d86b7b7b413eb15ec4301e522cbf",
            "input": "The aim of this study was to determine the reasons for which erupted third molars (3M) are extracted in a sample of Mexican patients.', \"A retrospective cross-sectional study was performed on a sample of 83 patients attending exodontia (minor oral surgery) clinics of a public university in Mexico (Autonomous University of Hidalgo State). The outcome variable was the reason for extractions using Kay and Blinkhorn's classification. The independent variables were age, gender, arch and tooth number according to the World Health Organization (WHO). For statistical analysis, we used the Chi-squared test in Stata 9.0.\", 'Eighty-three patients underwent 150 3M extractions. Mean age was 38.67 \u00b1 13.96 years, and 71.1% were female. The four reasons for 3M extraction were prosthetic (44.0%), followed by orthodontic (24.7%), dental caries (20.0%) and periodontal disease (11.3%). Differences were observed in the reasons for 3M extractions across age groups (p < 0.05). No significant differences existed between men and women (p > 0.05), or the WHO tooth number (p > 0.05).",
            "output": [
                "Are reasons why erupted third molars extracted in a public university in Mexico?"
            ]
        },
        {
            "id": "task847-61c37cfc802c4c68b1fb4095a8c50876",
            "input": "To measure the through-focus curve for eyes implanted with a type 1 Boston keratoprosthesis (KPro) and compare it to that of pseudophakic controls with fixed pupil sizes. The results should assist in evaluating postoperative visual quality after surgery. They should also help to determine the necessary KPro inventories in terms of refractive power steps.', 'Autorefraction and manifest refraction were performed on all eyes. The monocular through-focus acuity curve was plotted in reference to the best-corrected visual acuity by spectacle plane defocus ranging from +5.00 to -5.00\\xa0dioptres in 0.50\\xa0dioptre increments. These measurements were obtained on KPro-implanted eyes, pseudophakic eyes as controls, and on the same control eyes after fixing the pupil diameter to 3 and 2\\xa0mm using black painted iris contact lenses.', 'Ten KPro eyes and five control eyes were included. Good agreement was noted between the subjective refractions and autorefraction in KPro eyes. The average through-focus curve for the control eyes was significantly steeper than that of the KPro curve, but became comparable after fixing the control pupil to 2 and 3\\xa0mm.",
            "output": [
                "Does the Boston keratoprosthesis provide a wide depth of focus?"
            ]
        },
        {
            "id": "task847-63819caaff574688ad76a810438f830c",
            "input": "Larger food portions lead to increased intake but the mechanism behind this effect is unclear. We investigated the effect of portion size on bite size, eating rate, deceleration rate, and meal duration.', 'Thirty-seven overweight women attended 5 visits after a 3 h fast and consumed a 229, 303, 400, 529 or 700 g portion of a lunch meal in random order. Meal eating parameters were measured with the Sussex Ingestion Pattern Monitor. Data were analyzed with mixed effects models.', 'Average bite size increased by 0.22 g for every 100 g increase in portion size (p=0.001); portion size had a non-linear effect on eating rate, increasing with portion sizes up to about 540 g (p=0.01). Deceleration rate (reduction in speed of eating) decreased by 20% (p<0.001) and meal duration increased by 22.5% for every 100 g increase in portion size (p<0.001), relative to the smallest portion.",
            "output": [
                "Do large portion sizes increase bite size and eating rate in overweight women?"
            ]
        },
        {
            "id": "task847-8ee33063ac3747da81cddb238d484cea",
            "input": "Pre-operative restaging CT scans are often performed routinely following neoadjuvant chemoradiotherapy for locally advanced rectal cancer. There is a paucity of data on the utility of this common practice. We sought to determine how often restaging CTs identified disease progression or regression that altered management.', 'We performed a single-institution retrospective study. From 2007 to 2011, 182 patients had newly-diagnosed, non-metastatic rectal adenocarcinoma, of which 96 were surgical candidates with clinical stage II/III disease. Ninety-one of these patients (95%) completed neoadjuvant chemoradiation.', 'Eighty-three out of 91 patients (91%) had restaging CTs. Four patients (5%) had new lesions suspicious for distant metastasis (2 lung, 2 liver) on restaging CT scan reports (1 of these was present on initial staging CT but not reported). All 4 patients had node-positive disease. In no case did restaging CT result in a change in surgical management.",
            "output": [
                "Are routine preoperative restaging CTs after neoadjuvant chemoradiation for locally advanced rectal cancer low yield : a retrospective case study?"
            ]
        },
        {
            "id": "task847-22bd2b9d030549c699856efe390d4a96",
            "input": "Plasma levels of pancreatic polypeptide (PP) rise upon food intake. Although other pancreatic islet hormones, such as insulin and glucagon, have been extensively investigated, PP secretion and actions are still poorly understood.', 'The release of PP upon glucose stimulation and the effects of PP on glucagon and insulin secretion were analyzed in isolated pancreatic islets. Expression of PP receptor (PPYR1) was investigated by immunoblotting, quantitative RT-PCR on sorted pancreatic islet cells, and immunohistochemistry.', 'In isolated mouse pancreatic islets, glucose stimulation increased PP release, while insulin secretion was up and glucagon release was down. Direct exposure of islets to PP inhibited glucagon release. In mouse islets, PPYR1 protein was observed by immunoblotting and quantitative RT-PCR revealed PPYR1 expression in the FACS-enriched glucagon alpha-cell fraction. Immunohistochemistry on pancreatic sections showed the presence of PPYR1 in alpha-cells of both mouse and human islets, while the receptor was absent in other islet cell types and exocrine pancreas.",
            "output": [
                "Does pancreatic polypeptide regulate glucagon release through PPYR1 receptors expressed in mouse and human alpha-cells?"
            ]
        },
        {
            "id": "task847-4c1631b8ab014ca4872d03acf61ac4b2",
            "input": "To review UK newspaper reports relating to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decisions in order to identify common themes and encourage dialogue.', 'An online media database (LexisNexis(\u00ae)) was searched for UK Newspaper articles between 1993 and 2013 that referenced DNACPR decisions. Legal cases, concerning resuscitation decisions, were identified using two case law databases (Lexis Law(\u00ae) and Westlaw(\u00ae)), and referenced back to newspaper publications. All articles were fully reviewed.', 'Three hundred and thirty one articles were identified, resulting from 77 identifiable incidents. The periods 2000-01 and 2011-13 encompassed the majority of articles. There were 16 high-profile legal cases, nine of which resulted in newspaper articles. Approximately 35 percent of newspaper reports referred to DNACPR decisions apparently made without adequate patient and/or family consultation. \"Ageism\" was referred to in 9 percent of articles (mostly printed 2000-02); and \"discrimination against the disabled\" in 8 percent (mostly from 2010-12). Only five newspaper articles (2 percent) discussed patients receiving CPR against their wishes. Eighteen newspaper reports (5 percent) associated DNACPR decisions with active euthanasia.",
            "output": [
                "Do two decades of British newspaper coverage regarding attempt cardiopulmonary resuscitation decisions : Lessons for clinicians?"
            ]
        },
        {
            "id": "task847-d144e9fedf6b45cbadfbc532156e185d",
            "input": "The interval between neoadjuvant chemoradiation treatment and surgery has been described as an important predictor of pathologic response to therapy in nonesophageal cancer sites. We retrospectively reviewed our experience with patients who underwent neoadjuvant chemoradiation and esophagectomy to better understand the impact of the timing of surgery on pathologic complete response rates in esophageal cancer.', 'Two hundred thirty-one sequentially treated patients from 2000 to 2011 were identified for this study; 88 of these patients completed neoadjuvant chemoradiation followed by esophagectomy at our institution. The interval between completion of chemoradiation and surgery was calculated for each patient. The patients were categorized into quartiles and also into 3-week interval groups. Treatment factors and surgical morbidity data, including the estimated blood loss and length of operative stay, were also assessed.', 'Quartiles for the neoadjuvant chemoradiation to surgery interval were less than 45 days, 46 to 50 days, 51 to 63 days, and 64+ days. Corresponding pathologic complete response rates were 12.5%, 20.0%, 22.7%, and 40.9% (p = 0.03). Results for 3-week intervals were similar (p = 0.02). There was no association between increasing time interval between the ending of neoadjuvant chemoradiation to surgery and length of stay longer than 2 weeks.",
            "output": [
                "Is increased time from neoadjuvant chemoradiation to surgery associated with higher pathologic complete response rates in esophageal cancer?"
            ]
        },
        {
            "id": "task847-d5fded212a1449c5968ede1b955741ad",
            "input": "To investigate whether epileptogenic focus localization is possible based on resting state connectivity analysis of magnetoencephalographic (MEG) data.', 'A multivariate autoregressive (MVAR) model was constructed using the sensor space data and was projected to the source space using lead field and inverse matrix. The generalized partial directed coherence was estimated from the MVAR model in the source space. The dipole with the maximum information inflow was hypothesized to be within the epileptogenic focus.', 'Applying the focus localization algorithm (FLA) to the interictal MEG recordings from five patients with neocortical epilepsy, who underwent presurgical evaluation for the identification of epileptogenic focus, we were able to correctly localize the focus, on the basis of maximum interictal information inflow in the presence or absence of interictal epileptic spikes in the data, with three out of five patients undergoing resective surgery and being seizure free since.",
            "output": [
                "Is epileptic focus localization based on resting state interictal MEG recordings feasible irrespective of the presence or absence of spikes?"
            ]
        },
        {
            "id": "task847-24bb711fd6104d08ac1a3251f971d844",
            "input": "To assess the effect of treatment of seminal Helicobacter pylori in infertile asthenozoospermic men.', 'In all, 223 infertile asthenozoospermic men were consecutively selected. They were subjected to history taking, clinical examination, semen analysis, and estimation of H pylori IgA antibodies in their seminal fluid. Infertile men with high seminal H pylori IgA were subjected to triple drug treatment, omeprazole, 20 mg; tinidazole, 500 mg; and clarithromycin, 250 mg twice a day for 2 weeks. Semen analysis as well as H pylori IgA antibodies was estimated after 3 months.', 'In all, 22 of 223 men (9.87%) demonstrated H pylori IgA antibodies in their seminal plasma. After treatment, mean seminal H pylori IgA levels demonstrated significant decrease (1.55 \u00b1 0.4 vs 0.52 \u00b1 0.26; 95% confidence interval, 0.83-1.21; P = .001) concomitant with improved progressive as well as nonprogressive sperm motility. H pylori IgA antibodies demonstrated significant negative correlation with progressive sperm motility, nonprogressive sperm motility, normal sperm morphology, and significant positive correlation with immotile sperm motility.",
            "output": [
                "Does seminal Helicobacter pylori treatment improve sperm motility in infertile asthenozoospermic men?"
            ]
        },
        {
            "id": "task847-c26671daf03d4a88894c572271bcc61e",
            "input": "In most cells, the cilium is formed within a compartment separated from the cytoplasm. Entry into the ciliary compartment is regulated by a specialized gate located at the base of the cilium in a region known as the transition zone. The transition zone is closely associated with multiple structures of the ciliary base, including the centriole, axoneme, and ciliary membrane. However, the contribution of these structures to the ciliary gate remains unclear.', 'Here we report that, in Drosophila spermatids, a conserved module of transition zone proteins mutated in Meckel-Gruber syndrome (MKS), including Cep290, Mks1, B9d1, and B9d2, comprise a ciliary gate that continuously migrates away from the centriole to compartmentalize the growing axoneme tip. We show that Cep290 is essential for transition zone composition, compartmentalization of the axoneme tip, and axoneme integrity and find that MKS proteins also delimit a centriole-independent compartment in mouse spermatids.",
            "output": [
                "Does a migrating ciliary gate compartmentalize the site of axoneme assembly in Drosophila spermatids?"
            ]
        },
        {
            "id": "task847-e91e9a79dfc64fa0b6ad4970cb1b6598",
            "input": "Active commuters have lower risk of chronic disease. Understanding which of the, to some extent, modifiable characteristics of public transportation that facilitate its use is thus important in a public health perspective. The aim of the study was to examine the association between individual public transportation accessibility and self-reported active commuting, and whether the associations varied with commute distance, age, and gender.', 'Twenty-eight thousand nine hundred twenty-eight commuters in The Capital Region of Denmark reported self-reported time spent either walking or cycling to work or study each day and the distance to work or study. Data were obtained from the Danish National Health Survey collected in February to April 2010. Individual accessibility by public transportation was calculated using a multi-modal network in a GIS. Multilevel logistic regression was used to analyze the association between accessibility, expressed as access area, and being an active commuter.', 'Public transport accessibility area based on all stops within walking and cycling distance was positively associated with being an active commuter. Distance to work, age, and gender modified the associations. Residing within 10\\u2009km commute distance and in areas of high accessibility was associated with being an active commuter and meeting the recommendations of physical activity. For the respondents above 29\\u2009years, individual public transportation accessibility was positively associated with being an active commuter. Women having high accessibility had significantly higher odds of being an active commuter compared to having a low accessibility. For men, the associations were insignificant.",
            "output": [
                "Is individual Public Transportation Accessibility Positively Associated with Self-Reported Active Commuting?"
            ]
        },
        {
            "id": "task847-7a9a0440144540e485250f92ed6f33fd",
            "input": "Pathophysiological mechanisms leading to chordee in patients with hypospadias and to the hidden state of buried penis in the prepubic fat remain unclear. Resection of dartos tissue usually makes the penis straight in patients with hypospadias and corrects it in those with buried penis, suggesting a common pathophysiology related to dartos tissue.', 'Tissue samples from 113 children undergoing primary penile surgery for hypospadias (94 patients), epispadias (1) or buried penis (18) were collected between November 2011 and September 2013. Tissue samples from 79 children undergoing circumcision for nonmedical reasons served as controls. All samples were stained with smooth muscle actin and analyzed by the same pathologist, who was blinded to indication for surgery. Chi-square and Fisher exact tests were applied.', 'Three different dartos tissue patterns were observed. Pattern I (normal) consisted of smooth muscle fibers of dartos tissue organized in a parallel configuration in the subcutaneous tissue. Pattern II was characterized by poorly developed and hypotrophic smooth muscle fibers. Pattern III was determined by randomly distributed smooth muscle fibers in the subcutaneous tissue, without parallel configuration. Pattern I was observed in 45 circumcision specimens (64%). Of buried penis cases 78% were considered abnormal (pattern II in 4 cases and III in 10, p = 0.001). Of hypospadias cases 70% were considered abnormal (pattern II in 31 cases, III in 32, and mixed II and III in 3, p < 0.001). The only epispadias case was designated pattern II.",
            "output": [
                "Is congenital penile pathology associated with abnormal development of the dartos muscle : a prospective study of primary penile surgery at a tertiary referral center?"
            ]
        },
        {
            "id": "task847-6cbb97ad2f7e4f969b49fdacb0d0519f",
            "input": "Several risk factors have been claimed to predict the progression of clinically high grade T1 bladder tumors. However, these factors are not specific enough to define which patients should be treated immediately with radical cystectomy. Therefore, it is critical to identify molecular markers that can help provide individualized, risk stratified decision making. Our main goal was to evaluate the role of total p63, p53 and \u0394Np63 expression in cases of clinically high grade T1 bladder cancer progression.', 'Total p63, p53 and \u0394Np63 expression was analyzed by immunohistochemistry in 134 clinically high grade T1 tumors. We assessed clinical progression to muscle invasive disease or radical cystectomy as a patient outcome end point. Survival analysis was done for recurrence-free, progression-free, disease specific and overall survival.', 'A total of 132 patients (98.5%) underwent repeat transurethral resection. Cases of early progression (less than 3 months) were excluded from study to avoid under staging. Of the tumors 90 (67.2%) showed \u0394Np63 expression loss. During a median followup of 62.1 months 19 patients (14.2%) progressed to muscle invasive disease. The progression rate was 21.1% in patients with tumors characterized by \u0394Np63 loss but no progression was observed in those with tumors with \u0394Np63 expression (p <0.001). There was no difference in the number of patients who underwent repeat transurethral resection, had associated carcinoma in situ, showed lymphovascular invasion or received followup intravesical bacillus Calmette-Gu\u00e9rin courses.",
            "output": [
                "Is \u03b4Np63 expression a protective factor of progression in clinical high grade T1 bladder cancer?"
            ]
        },
        {
            "id": "task847-afef5fd647c14e24a96ab03ec11e8aae",
            "input": "To date, no data is available about procalcitonin (PCT) levels and its relevance to morbidity and graft function in the early phase after pediatric liver transplantation (pLTx). The aim of this study was to analyse the prognostic relevance of early postoperative PCT elevations in pediatric liver recipients.', 'Thirty pediatric patients who underwent 32 liver transplantations were included into this observational single-center study.', 'Patients with high PCT levels on postoperative day (POD) 2 had higher International Normalized Ratio values on POD 5 (p<0.05) and suffered more often from primary graft non-function (p<0.05). They also had a longer stay in the pediatric intensive care unit (p<0.01) and on mechanical ventilation (p=0.001). There was no correlation between PCT elevation and systemic infection. However, PCT levels were correlated with peak serum lactate levels immediately after graft reperfusion and elevation of serum aminotransferases on POD 1 (r2=0.61, p<0.001).",
            "output": [
                "Do high levels of procalcitonin in the early phase after pediatric liver transplantation indicate poor postoperative outcome?"
            ]
        },
        {
            "id": "task847-901777dc352045909c18ef62ce96c4e3",
            "input": "The purpose of this study was to assess liver-type fatty acid-binding protein (L-FABP) expression and its association with clinicopathological features in hepatocellular carcinoma (HCC).', 'L-FABP mRNA expression in 57 samples of HCC and corresponding adjacent liver tissue and 8 normal liver tissue samples were examined by real-time reverse transcriptase (RT)\u2013PCR analyses. Tissue microarray technique and immunohistochemistry (IHC) were used to detect the expression of L-FABP in 163 HCCs. The association between L-FABP expression and the clinicopathological factors and prognosis was analyzed.', 'The average expression of L-FABP mRNA was 0.233 in the HCC tissues, 1.407 in the peri-carcinoma tissues, and 1.0 in the normal liver tissues. IHC analysis showed that there were 47% (76/163) HCCs exhibited weak or even no immunoreactivity of L-FABP. The L-FABP expression in HCC showed significant associations with preoperative levels of AFP (p=0.039), tumor size (p=0.026), histological grade (p=0.000), differential degree (p=0.000), vascular invasion (p=0.016), capsular invasion (p=0.029) and recurrence (p=0.004). Patients with L-FABP high-expression showed better prognosis than patients with L-FABP low-expression (p=0.008).",
            "output": [
                "Is decreased expression of liver-type fatty acid-binding protein associated with poor prognosis in hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-190038b0b7c849f58156d4c66abb6a9b",
            "input": "Vein bypass is an essential therapy for patients with advanced peripheral and coronary artery disease despite development of neointimal hyperplasia. We have shown that stimulation of the receptor tyrosine kinase ephrin type-B receptor 4 (Eph-B4) with its ligand ephrin-B2 prevents neointimal hyperplasia in murine vein grafts. This study determines whether Eph-B4 in adult human veins is capable of phosphorylation and activation of downstream signaling pathways, as well as functional to release nitric oxide (NO) and prevent neointimal hyperplasia in vitro.', 'Discarded human saphenous veins were taken from the operating room and placed in organ culture without or with ephrin-B2/Fc (2 \u03bcg/mL) for 14 days, and the neointima/media ratio was measured in matched veins. Primary human umbilical vein endothelial cells were treated with ephrin-B2/Fc (2 \u03bcg/mL) and examined with quantitative polymerase chain reaction, Western blot, immunoassays, and for release of NO. Ephrin-B2/Fc (2 \u03bcg/mL) was placed on the adventitia of saphenous veins treated with arterial shear stress for 24 hours in a bioreactor and activated Eph-B4 examined with immunofluorescence.', 'The baseline intima/media ratio in saphenous vein rings was 0.456 \u00b1 0.097, which increased to 0.726 \u00b1 0.142 in untreated veins after 14 days in organ culture but only to 0.630 \u00b1 0.132 in veins treated with ephrin-B2/Fc (n = 19, P = .017). Ephrin-B2/Fc stimulated Akt, endothelial NO synthase and caveolin-1 phosphorylation, and NO release (P = .007) from human umbilical vein endothelial cells (n = 6). Ephrin-B2/Fc delivered to the adventitia stimulated endothelial Eph-B4 phosphorylation after 24 hours of arterial stress in a bioreactor (n = 3).",
            "output": [
                "Does ephrin type-B receptor 4 activation reduce neointimal hyperplasia in human saphenous vein in vitro?"
            ]
        },
        {
            "id": "task847-6aed91cec223410d941226f5f1e9890a",
            "input": "Low serum levels of vitamin D have been associated with depression in non-stroke subjects. Our aim was to examine the possible association between serum vitamin D levels and the development of post-stroke depression (PSD).', 'In total, 189 patients with acute ischaemic stroke were consecutively recruited. Serum levels of 25-hydroxyvitamin D [25(OH)D] were measured by competitive protein-binding assay within 24 h after admission. The 17-item Hamilton Depression Scale was used for screening for the existence of depressive symptoms at 1 month after stroke. Patients with a Hamilton Depression Scale score of \u22657 were given the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for diagnosis of PSD. Meanwhile, 100 healthy control subjects were also recruited and underwent measurement of 25(OH)D.', 'Fifty-five patients (29.1%) were diagnosed as having PSD at 1 month. Serum vitamin D levels within 24 h after admission were significantly lower in both non-PSD patients and PSD patients than in normal controls. PSD patients had significantly lower vitamin D than non-PSD patients. Serum vitamin D levels (\u226437.1 and \u226564.1 nmol/l) were independently associated with the development of PSD (odds ratio 8.824, 95% confidence interval 2.011-38.720, P = 0.004, and odds ratio 0.127, 95% confidence interval 0.022-0.718, P = 0.020, respectively).",
            "output": [
                "Are low serum levels of vitamin D associated with post-stroke depression?"
            ]
        },
        {
            "id": "task847-a9654a0e31c04af9b456279e5b780098",
            "input": "Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.\", 'We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.', 'We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 \u00d7 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 \u00d7 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 \u00d7 10(-9)).",
            "output": [
                "Are polymorphisms near TBX5 and GDF7 associated with increased risk for Barrett 's esophagus?"
            ]
        },
        {
            "id": "task847-eb74045fcd2b44199ec350ef035269d5",
            "input": "Danzhi Xiaoyao San (DXS) is a canonical Chinese medicine formula from Principles of Internal Medicine, which was written during the Ming dynasty. This formula is approved and commercialized for use in the prevention and treatment of affective disorders. This study is aimed to investigate the hypothesis that DXS treats depressive-like behavior by shifting the balance of the kynurenine (Kyn)/serotonin (5-HT) pathway toward the 5-HT pathway through the downregulation of hippocampal indoleamine 2,3-dioxygenase (IDO).', 'Chemical fingerprints of gardenoside, paeoniflorin, ferulic acid, paeonol, and ligustilide in standard extraction were used as the material bases of DXS. Rats with depressive-like behavior induced by chronic unpredictable mild stress (CUMS) were randomly divided into four groups, namely the control, model, DXS, and fluoxetine groups. Cytokines, IDO, and tryptophan (Trp) catabolites were analyzed by enzyme-linked immunosorbent assay, western blot, and liquid chromatography-electrospray ionization tandem mass spectrometry, respectively.', 'DXS significantly increased crossing grid numbers, sucrose consumption, and body weight. This treatment significantly decreased the serum levels of tumor necrosis factor-\u03b1 and interleukin 6 (IL-6). However, DXS elicited no significant effects on IL-1\u03b2, IL-2, and interferon \u03b3. DXS downregulated the activity of IDO and subsequent production of Kyn in the hippocampus. This treatment upregulated the hippocampal contents of Trp and 5-HT but did not influence 5-HT turnover.",
            "output": [
                "Does danzhi Xiaoyao San ameliorate depressive-like behavior by shifting toward serotonin via the downregulation of hippocampal indoleamine 2,3-dioxygenase?"
            ]
        },
        {
            "id": "task847-9db50375713b48c48bad8074842fcd5b",
            "input": "Prostate cancer is the world's leading cause of cancer and the second cause of cancer-related death in men after lung cancer. Differentiation of prostate adenocarcinoma from benign prostate lesions and hyperplasia sometimes cannot be done on the basis of morphologic findings. Considering the fact that in the prostate adenocarcinoma there is no basal cell layer, basal cell markers can help to differentiate prostate adenocarcinoma from cancer mimickers.\", 'We studied 98 prostate biopsy blocks (40 adenocarcinoma and 58 benign lesions) for basal cell marker expression.', 'p63 and 34\u03b2E12 were negative in all prostate adenocarcinoma specimens, but all benign prostate hyperplasia and high grade intraepithelial neoplasia cases expressed them.",
            "output": [
                "Is p63 more sensitive and specific than 34\u03b2E12 to differentiate adenocarcinoma of prostate from cancer mimickers?"
            ]
        },
        {
            "id": "task847-8a3206c241a14cf79b30d760af0285c2",
            "input": "Disturbed sleep is associated with mood disorders. Both depression and insomnia may increase the risk of disability retirement. The longitudinal links among insomnia, depression and work incapacity are poorly known.', 'We examined association of self-reported sleep quality with incident symptoms of depression and disability retirement due to depressive disorders in a longitudinal population-based sample of twins (n=12,063 individuals). These adults were categorized by their sleep quality in 1975 and 1981, excluding individuals with depressed mood in 1975/1981. The outcomes were the Beck Depression Inventory (BDItot) and its subscale Negative Attitudes Towards Self (BDINATS) in 1990 as dichotomized measures, and the incidence of disability retirement due to depressive disorder during 1991-2004.', 'Onset of poor sleep between 1975 and 1981 predicted incident depression (BDItot OR=4.5, 95% CI: 2.7-7.4, BDINATS OR=2.0, 95% CI: 1.4-2.7), while persistent poor sleep showed somewhat weaker effects (BDItot; OR=2.5, 95% CI: 1.0-6.0, BDINATS OR=1.9, 95% CI: 1.1-3.3). Among those with few recent stressful life events, onset of poor sleep predicted strongly depression (BDINATS OR=9.5, 95% CI: 3.7-24.2). Likewise onset of poor sleep by 1981 increased the risk of disability retirement due to depression (OR=2.9, 95% CI: 1.8-4.9) with a similar risk among those with persistent poor sleep (OR=2.7, 95% CI: 1.3-5.7).",
            "output": [
                "Does poor sleep predict symptoms of depression and disability retirement due to depression?"
            ]
        },
        {
            "id": "task847-dc5ff24f80ab48c4adaf798ff684b05a",
            "input": "Phospholipase C epsilon 1 (PLCE1) plays a crucial role in carcinogenesis and progression of several types of cancers. A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus. The aim of the present study was to investigate the role of three potentially functional SNPs (rs2274223A > G, rs3765524C > T, and rs7922612C > T) of PLCE1 in gastric cancer patients from Kashmir Valley.', 'The study was conducted in 108 GC cases and 195 healthy controls from Kashmir Valley. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed using c2 test and logistic regression models. A P value of less than 0.05 was regarded as statistically significant.', 'The frequency of PLCE1 A2274223C3765524T7922612, G2274223C3765524T7922612 , and G2274223T3765524C7922612 haplotypes were higher in patients compared with controls, conferred high risk for GC [odds ratio (OR) =6.29; P = 0.001; Pcorr = 0.003], (OR = 3.23; P = 0.011; Pcorr = 0.033), and (OR = 5.14; P = 0.011; Pcorr = 0.033), respectively. Smoking and salted tea are independent risk factors for GC, but we did not find any significant modulation of cancer risk by PLCE1 variants with smoking or excessive consumption of salted tea.",
            "output": [
                "Are phospholipase C epsilon 1 ( PLCE1 ) haplotypes associated with increased risk of gastric cancer in Kashmir Valley?"
            ]
        },
        {
            "id": "task847-9bad93cfdae54fa5924e02723de3e3b9",
            "input": "Esophageal squamous cell carcinoma (ESCC) is an important cause of cancer-related death worldwide. To improve prognoses in patients with ESCC, we evaluated the potential of transforming growth factor-beta-induced protein (TGFBI), which is overexpressed in ESCC, as a therapeutic candidate.', 'We examined the clinical significance of TBFBI in 102 ESCC samples using real-time RT-PCR. Immunohistochemical studies were conducted to examine the localization of TGFBI. Knockdown of TGFBI in cocultured fibroblasts was performed to determine the roles of TGFBI in migration and invasion.', 'The level of TGFBI in ESCC tissues was higher than that in normal tissues. The high TGFBI expression group (n = 16) had higher TGFB1 expression and more frequent hematogenous recurrence than the low-expression group (n = 86). High TGFBI expression was an independent prognostic factor in patients with ESCC. TGFBI was mainly localized in stromal cells of ESCC. Moreover, suppression of TGFBI in fibroblasts inhibited the migration and invasion capacity of TE8 ESCC cells.",
            "output": [
                "Is tGFBI Expression in Cancer Stromal Cells Associated with Poor Prognosis and Hematogenous Recurrence in Esophageal Squamous Cell Carcinoma?"
            ]
        },
        {
            "id": "task847-9f2d938c53b6407dae91aa8a236dcc86",
            "input": "Chronic antibiotic-refractory pouchitis (CARP) occurs more frequently in patients with ileal pouch-anal anastomosis (IPAA) with concomitant autoimmune disorders. The aim of this study was to assess the overlap between dysregulated immune features in patients with IPAA and their association with CARP.', 'We identified 150 symptomatic patients with IPAA who met inclusion criteria, including measurement of select autoimmune serology. Demographic and clinical variables were compared between patients with and without CARP.', 'Autoimmune thyroid disease was more frequent among patients with CARP. The frequency of primary sclerosing cholangitis (16.7% versus 5.3%; P = 0.04) and serum positivity for microsomal antibody (25% versus 6.1%, P = 0.003) were significantly greater in patients with CARP compared with non-CARP patients, respectively. Increased tissue infiltration by IgG4-expressing plasma cells was detected in 17 of 31 patients (54.8%) in the CARP group as compared with 10/67 (14.9%) in the non-CARP group (P = 0.0001). Forty-seven percent of patients in the CARP group versus 22.8% in the non-CARP group had at least 2 immune features (P = 0.019). Among patients with IgG4 histology, 87% of patients in the CARP group versus 60% in the non-CARP group had at least 1 immune marker (P = 0.004). On multivariate analysis, microsomal antibody expression (odds ratio, 6.8; 95% confidence interval, 1.3-42.6; P = 0.02) and increased IgG4-expressing plasma cells tissue infiltration (odds ratio, 9.6; 95% confidence interval, 3.2-32.6, P = 0.0001) were risk factors for CARP.",
            "output": [
                "Are autoimmune features associated with chronic antibiotic-refractory pouchitis?"
            ]
        },
        {
            "id": "task847-a4262f9fefb84c7b8923501f306d5595",
            "input": "Alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism are two separate movement disorders with different dominant mutations in the same sodium-potassium transporter ATPase subunit gene, ATP1A3.', 'We present a child with topiramate-responsive alternating hemiplegia of childhood who was tested for an ATP1A3 gene mutation.', 'Gene sequencing revealed an identical ATP1A3 mutation as in three typical adult-onset rapid-onset dystonia parkinsonism cases but never previously described in an alternating hemiplegia of childhood case.",
            "output": [
                "Does identical ATP1A3 mutation cause alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism phenotypes?"
            ]
        },
        {
            "id": "task847-3f7f890f619e4c27a8e34b03f4afd049",
            "input": "The principal oxidative-stress defense in the human parasite Trypanosoma cruzi is the tryparedoxin-dependent peroxide detoxification pathway, constituted by trypanothione reductase (TryR), tryparedoxin (TXN), tryparedoxin peroxidase (TXNPx) and tryparedoxin-dependent glutathione peroxidase A (GPxA). Here, Metabolic Control Analysis (MCA) was applied to quantitatively prioritize drug target(s) within the pathway by identifying its flux-controlling enzymes.', 'The recombinant enzymes were kinetically characterized at physiological pH/temperature. Further, the pathway was in vitro reconstituted using enzyme activity ratios and fluxes similar to those observed in the parasites; then, enzyme and substrate titrations were performed to determine their degree of control on flux. Also, kinetic characterization of the whole pathway was performed.', 'Analyses of the kinetic properties indicated that TXN is the less efficient pathway enzyme derived from its high Kmapp for trypanothione and low Vmax values within the cell. MCA established that the TXN-TXNPx and TXN-GPxA redox pairs controlled by 90-100% the pathway flux, whereas 10% control was attained by TryR. The Kmapp values of the complete pathway for substrates suggested that the pathway flux was determined by the peroxide availability, whereas at high peroxide concentrations, flux may be limited by NADPH.",
            "output": [
                "Does metabolic control analysis of the Trypanosoma cruzi peroxide detoxification pathway identify tryparedoxin as a suitable drug target?"
            ]
        },
        {
            "id": "task847-ff476c58748d48fbb0b286c35c3149bc",
            "input": "The role of Kdr (VEGFR-2/Flk-1) in vascular formation has been well described, but the role of Flt1 (VEGFR-1) is not well studied and is generally considered as a decoy receptor for trapping VEGF.', 'The effects of VEGFR1/2 kinase inhibitor (VRI) and calycosin on Flt1 tyrosine kinase (TK) activity were evaluated by molecular docking, enzymatic inhibition assay, protein co-immunoprecipitation and siRNA gene knock-down analysis in HUVECs. Toxicities of the chemicals were examined using HUVECs viability. Their effects on angiogenesis and vessel formation were furthered studied in HUVECs in vitro and Tg(fli-1:EGFP) zebrafish in vivo. The gene and protein expression of VEGF and VEGF receptors were investigated by quantitative RT-PCR and Western blot.', 'VRI strongly inhibited physiological functions of both VEGF receptors and suppressed endothelial cell survival. This resulted in blood vessel loss in zebrafish embryos. Interestingly, calycosin co-treatment impeded VRI-induced blood vessel loss. Docking and kinase inhibition assay revealed that calycosin competed with VRI for the tyrosine kinase domain of Flt1 without affecting ATP binding. On the contrary, calycosin did not affect the interaction between VRI and Kdr-TK. Consistent with these results, calycosin counteracted the inhibition of Flt1-TK and PI3K phosphorylation induced by VRI in HUVECs. Further studies in vitro and in vivo showed that the minimizing effect of calycosin on VRI-mediated endothelial cytotoxicity was blocked by wortmannin (a PI3K inhibitor). The impeding effect of calycosin on VRI-induced blood vessel loss was absent in zebrafish embryos injected with Flt1 MO.",
            "output": [
                "Is basal Flt1 tyrosine kinase activity a positive regulator of endothelial survival and vascularization during zebrafish embryogenesis?"
            ]
        },
        {
            "id": "task847-ab8685f5ccc3473ebbbd1084ba3ce88f",
            "input": "The capacity of toll-like receptor (TLR) 7/8 agonist-conjugated hepatitis B virus (HBV) proteins (HBV-Ag) to overcome established hepatitis B surface antigen (HBsAg)-specific immune tolerance was explored.', 'A TLR7/8 agonist, CL097, was conjugated with alum-absorbed HBsAg and hepatitis B core antigen (HBcAg), as confirmed by ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS). Mice from two independently generated HBV-transgenic (HBV-Tg) colonies, C57BL/6J-TgN (AlblHBV) 44Bri/J mice and C57BL/6-HBV-1.3 genome-eq mice, were immunized with CL097-conjugated HBV-Ag every 2 weeks, four times.', 'After immunization, 8/11 (72.7%) of the AlblHBV mice and 10/13 (76.9%) of the HBV-1.3 genome-eq mice generated serum detectable antibodies against HBsAg (anti-HBs). HBsAg-specific interferon gamma (IFN-\u03b3)-producing CD4(+) and CD8(+) T-cells were detected in splenocytes from these mice. Na\u00efve normal mice receiving splenocytes from the mice immunized with CL097-conjugated HBV-Ag generated immediate recall immune responses, e.g., the mice that received CD4(+)CD25(+)-depleted splenocytes generated anti-HBs on day 3 after HBsAg challenge while those receiving cells from sham-immunized mice did not.",
            "output": [
                "Do immunizations with hepatitis B viral antigens and a TLR7/8 agonist adjuvant induce antigen-specific immune responses in HBV-transgenic mice?"
            ]
        },
        {
            "id": "task847-141c35f8db4f4612b98338323b876997",
            "input": "Normal aging is associated with a decline in cognitive abilities, particularly in the domains of psychomotor speed and executive functioning. However, 'aging,' per se, is not a cause of cognitive decline but rather a variable that likely captures multiple accumulating biological changes over time that collectively affect mental abilities. Recent work has focused on the role of cerebrovascular disease as one of the biological changes. In the current study, we examined whether lobar microbleeds - magnetic resonance imaging (MRI) signal voids due to hemosiderin deposits secondary to cerebral amyloid angiopathy - are associated with cognitive decline in normal aging. Previous studies that reported a relationship between the presence of lobar microbleeds and decreased cognitive abilities have been primarily cross-sectional. Here, we used a retrospective longitudinal design to examine whether the presence of lobar microbleeds is associated with the rate of cognitive decline among non-demented older adults.\", 'Participants came from an ongoing longitudinal community-based aging study, in which subjects are evaluated at 18-24 months intervals and received a full medical, neurological, and neuropsychological examination at each of the follow-up visits. Gradient echo MRI scans were available on 197 non-demented participants (mean age: 84.15 \u00b1 5.02 years). Microbleeds were rated visually on axial view and divided into subcortical (basal ganglia, cerebellum) and lobar (frontal, temporal, parietal, occipital lobe) regions, and confirmed with coronal and sagittal views to exclude artifacts. Cognition was assessed with a neuropsychological battery, providing summary scores for memory, language, executive, and visuospatial abilities. Using general estimating equations (GEE), we compared cognition cross-sectionally between individuals with 2 or more (n = 11) and fewer than 2 (n = 186) lobar microbleeds and examined longitudinal cognitive change beginning 9.47 \u00b1 3.13 years before the MRI scan.', 'Subjects with 2 or more lobar microbleeds had worse executive functioning at the visit closest to the MRI scan (\u03b2 = -0.044; p < 0.001) and had a faster decline in executive function over time (\u03b2 = -0.072; p = 0.012) than subjects with fewer than 2 lobar microbleeds. The two groups were similar in age at scan date, education, ethnicity, sex distribution, and cognitive performance at first visit.",
            "output": [
                "Are lobar microbleeds associated with a decline in executive functioning in older adults?"
            ]
        },
        {
            "id": "task847-5db22a4dabea468aa40cfbaeb9815907",
            "input": "In recent years, the relationship between physical activity (PA) and smoking cessation has been increasingly studied. However, very few studies have investigated the possible protective role of PA on smoking relapse on the long term.', 'This study evaluated the impact of self-reported PA in precessation on smoking relapse. Other variables evaluated included measures of dependence, socio-demographic factors and smoking-related variables. Several possible interactions between PA and well identified factors influencing smoking relapse rate were also explored.', 'After the initial consultation, 345 smokers were consecutively recruited in a smoking-cessation unit. Smoking abstinence was collected regularly during consultation or by phone calls. PA was measured with the International Physical Activity Questionnaire short form. Cox proportional hazard model was performed to determine factors associated with smoking relapse.', 'Among the initial sample, 227 adults were included in the survival analysis. After adjustment for potential cofounders, PA was not associated with smoking relapse. Self-efficacy level, absence of professional activity, previous attempts to quit and alcohol use disorders were associated with relapse. Secondary analysis showed a statistically significant effect of an interaction term for PA and antidepressant use on reducing smoking relapse (HR\\u2009=\\u2009.81, 95% CI: .66-.99).",
            "output": [
                "Is self-reported physical activity in smoking pre-cessation a protective factor against relapse for all?"
            ]
        },
        {
            "id": "task847-a79da6686ee34a1bbf611d5a7293b8fc",
            "input": "Many assume that most patients hospitalized with heart failure (HF) are short of breath at rest (SOBAR). The National HF Audit for England and Wales suggests that this assumption is false, which has profound implications for management', 'A retrospective case-note review was carried out of patients hospitalized with HF to determine how many present with shortness of breath at rest or are comfortable at rest but breathless on slight exertion (CARBOSE). Vital signs were tracked for 24\\u2009h and mortality for 180 days. Of 311 patients, those who were SOBAR (42%) had higher median heart rate (HR) (100 vs. 85 b.p.m.; P\\u2009<\\u20090.001), systolic blood pressure (SBP) (141 vs. 122\\u2009mmHg; P\\u2009<\\u20090.001), and respiratory rate (RR) (24 vs. 18 breaths/min; P\\u2009<\\u20090.001) compared with those who were CARBOSE (56%). Vital signs changed little in those who were CARBOSE over the first 4-6\\u2009h, but SBP (141-128\\u2009mmHg; P\\u2009<\\u20090.001), HR (100-90 b.p.m.; P\\u2009=\\u20090.002), and RR (24-20 breaths/min; P\\u2009<\\u20090.001) fell in those who were SOBAR. At presentation, SBP was >125\\u2009mmHg in 73% of patients who were SOBAR and in 46% who were CARBOSE, dropping to 52% and 37%, respectively, by 4-6\\u2009h. Mortality amongst those who were SOBAR and those who were CARBOSE was, respectively, 19% and 34% (odds ratio 2.29; P\\u2009=\\u20090.005, 95% confidence interval 1.29-4.06).",
            "output": [
                "Is breathlessness at rest the dominant presentation of patients admitted with heart failure?"
            ]
        },
        {
            "id": "task847-7a619a3595034b259d441dee0272b85b",
            "input": "Duodenal stump disruption remains one of the most dreadful postgastrectomy complications, posing an overwhelming therapeutic challenge.', 'The present report describes the extremely rare occurrence of a delayed duodenal stump disruption following total gastrectomy with Roux-en-Y esophagojejunostomy for cancer, because of mechanical obstruction of the distal jejunum resulting in increased backpressure on afferent limp and duodenal stump. Surgical management included repair of distal jejunum obstruction, mobilization and re-stapling of the duodenum at the level of its intact second part and retrograde decompressing tube duodenostomy through the proximal jejunum.",
            "output": [
                "Is delayed duodenal stump blow-out following total gastrectomy for cancer : Heightened awareness for the continued presence of the surgical past in the present the key to a successful duodenal stump disruption management . A case report?"
            ]
        },
        {
            "id": "task847-fa05d6b37dd94ff9b60e30c972241842",
            "input": "Elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with both coronary artery and cerebrovascular diseases. The clinical diagnosis of neurovascular events, specifically transient ischemic attack can be challenging, although there is disagreement among vascular trained neurologists regarding this. Currently, there is no single accurate biomarker for the diagnosis of acute brain ischemia.', 'We studied the relationship between Lp-PLA2 mass and activity levels and the diagnosis of acute brain ischemia in the acute phase among patients evaluated in the emergency department following transient focal neurological symptoms.', 'Patients evaluated in our academic center for transient neurological symptoms of possible ischemic mechanism were enrolled with informed consent. Lp-PLA2 mass and activity levels were performed by DiaDexus, Inc.', '100 patients were enrolled: 58 were ischemic (30 stroke, 28 TIA), 10 were unknown, and 28 were non-ischemic. Blood samples were collected after a median delay of 23 h (IQR: 17, 36) after symptom onset. The median levels of Lp-PLA2 activity level for ischemic (stroke and TIA) versus non-ischemic events were 186.5 nmol/ml/min (IQR = 153, 216.3) and 169 nmol/ml/min (IQR = 137, 212.5), respectively. The median levels of Lp-PLA2 mass level for ischemic versus non-ischemic events were 202 ng/ml (IQR = 171.6, 226.1) and 192 ng/ml (167.8, 230). The differences in median Lp-PLA2 mass and activity levels were not statistically significant in the ischemic versus non-ischemic patients. Vessel imaging revealed a symptomatic stenosis in 14 patients (10 intracranial and 4 cervical). The median Lp-PLA2 mass and activity levels among patients with a symptomatic stenosis were not significantly higher than the levels measured in TIA/stroke patients without stenosis.",
            "output": [
                "Are lipoprotein phospholipase A2 mass and activity associated with the diagnosis of acute brain ischemia?"
            ]
        },
        {
            "id": "task847-3ef8ca67a43649388187a6f9f63a5efb",
            "input": "Recently, the role of osteoprotegerin (OPG) in the pathogenesis of heart failure through different mechanisms has received much attention. Subclinical changes in left ventricular (LV) function can be identified using quantification of myocardial strain, and global longitudinal strain (GLS) is a superior predictor of outcomes than ejection fraction. We hypothesized that increased OPG levels could predict subclinical LV systolic dysfunction in treated diabetic hypertensive patients with preserved LV ejection fraction.', 'The study was composed of 86 diabetic hypertensive and 30 nondiabetic hypertensive patients. All patients underwent echocardiography and venous blood samples were taken for determination of OPG. The relation between OPG levels and LV GLS was investigated using 2-dimensional speckle tracking echocardiography.', 'Diabetic hypertensive patients had higher diastolic peak early/early diastolic tissue velocity and lower systolic tissue velocity, GLS, GLS rate systolic, and GLS rate early diastolic than nondiabetic hypertensive patients (P = 0.009, P = 0.049, P < 0.001, P = 0.004, and P < 0.001, respectively). Diabetic hypertensive patients were divided into 2 groups according to median GLS value (> 18.5 and \u2264 18.5). The patients with GLS \u2264 18.5 had higher diastolic blood pressure (mm Hg; P = 0.048), OPG (pmol/L; P < 0.001), and hemoglobin A1c (%; P = 0.042) values than those with GLS > 18.5. In multivariate logistic regression analysis, OPG was found to be an independent predictor of impaired GLS (P = 0.001). Receiver operating characteristic curve analysis revealed that OPG values of > 6.45 (pmol/L) identified the patients with GLS \u2264 18.5.",
            "output": [
                "Is osteoprotegerin associated with subclinical left ventricular systolic dysfunction in diabetic hypertensive patients : a speckle tracking study?"
            ]
        },
        {
            "id": "task847-51e48aeba1d5453cb2e3c026da33ba3c",
            "input": "Burns are common and recurrent events treated by physicians on a daily basis at most emergency rooms around the world. There is a constant need to understand the physiopathology of burns, so as to minimize their devastating results. The objective of the present report is to describe a burn apparatus in association with an innovative method of animal fixation, as to produce burns of varying sizes and depths.', 'Rats were subjected to burns of 60 \u00b0C, 70 \u00b0C, and 80 \u00b0C for 10 s and after 3 days half of the rats in each group were killed and the resulting lesions were analyzed using histological techniques. In the other half of the rats the wound was measured weakly until complete re-epithelialization.', 'All burns were easily visible and the histological feature for the 60 \u00b0C burn was a superficial second-degree burn (28% of the dermis), for 70 \u00b0C we observed a deep second-degree burn (72% of the dermis), and in the 80 \u00b0C group, a third degree-burn was present (100% of the dermis).",
            "output": [
                "Do a new model for the standardization of experimental burn wounds?"
            ]
        },
        {
            "id": "task847-ecc995e0eadb4e1997d9e8f463fd7932",
            "input": "The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility.', 'Genotyping was performed across 16 000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single-nucleotide polymorphisms were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess the significance, in vitro functional genomic studies and clinical outcomes for carriers of a single-nucleotide polymorphism rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 55\u00b18% of wild-type protein (P=0.01) as assessed by quantitative western blots. Carriers of rs5063 had lower NT-proANP levels (1427 versus 2291 pmol/L; P<0.001) and higher diastolic blood pressures (75 versus 73 mm Hg; P=0.009) and were at an increased risk of stroke when compared with wild-type subjects independent of age, sex, diabetes mellitus, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio, 1.6; P=0.004).",
            "output": [
                "Does circulating atrial natriuretic peptide genetic association study identify a novel gene cluster associated with stroke in whites?"
            ]
        },
        {
            "id": "task847-895ebda0716c4d1085b9d03cbdeedc9c",
            "input": "Mycobacterium abscessus has emerged as a major pathogen in cystic fibrosis (CF) patients and has been associated with poor clinical outcomes, particularly following lung transplant. We investigated the acquisition of this bacterium in a cohort of pediatric CF patients.', 'Demographic and patient location data were used to uncover epidemiological links between patients with genetically related strains of M. abscessus that had been previously typed by variable-number tandem repeat profiling. Whole-genome sequencing was applied to 27 M. abscessus isolates from the 20 patients in this cohort to provide definitive data on the genetic relatedness of strains.', 'Whole-genome sequencing data demonstrated that M. abscessus isolates from 16 patients were unrelated, differing by at least 34 single-nucleotide polymorphisms (SNPs) from any other isolate, suggesting that independent acquisition events have occurred. Only 2 clusters of very closely related (<25 SNPs) isolates from different patients were seen. The first cluster contained 8 isolates, differing by a maximum of 17 SNPs, from a sibling pair who had intense exposure to each other both inside and outside the hospital. The second cluster contained 3 isolates, differing by a maximum of 24 SNPs, from 2 individuals with no apparent epidemiological links.",
            "output": [
                "Do whole-genome sequencing and epidemiological analysis provide evidence for cross-transmission of mycobacterium abscessus in a cohort of pediatric cystic fibrosis patients?"
            ]
        },
        {
            "id": "task847-f9bf8bb9dad24181b5aa7eb2c91fef5b",
            "input": "Bacterial vaginosis is a risk factor for preterm birth. The various conventional methods for its diagnosis are laborious and not easily reproducible. Molecular quantification methods have been reported recently, but the specific risk factors they might identify remain unclear.', 'A prospective multicenter national study included pregnant women at risk of preterm birth. A quantitative molecular tool using a specific real-time polymerase chain reaction assay and serial dilutions of a plasmid suspension quantified Atopobium vaginae, Gardnerella vaginalis, lactobacilli, Mycoplasma hominis, and the human albumin gene (for quality control).', 'In 813 pregnancies, high vaginal loads of either or both of A. vaginae and G. vaginalis were associated with preterm birth (hazard ratio [HR], 3.9; 95% confidence interval {CI}, 1.1-14.1; P = .031). A high vaginal load of A. vaginae was significantly associated with shortened time to delivery and therefore pregnancy length. These times were, respectively, 152.2 and 188.2 days (HR, 5.6; 95% CI, 1.5-21.3; P < .001) before 22 weeks, 149.0 and 183.2 days (HR, 2.8; 95% CI, 1.1-8.2; P = .048) before 28 weeks, and 132.6 and 170.4 days (HR, 2.2; 95% CI, 1.1-4.6; P = .033) before 32 weeks. After multivariate analysis, A. vaginae levels \u226510(8) copies/mL remained significantly associated with delivery before 22 weeks of gestation (adjusted HR, 4.7; 95% CI, .2-17.6; P = .014).",
            "output": [
                "Are high Atopobium vaginae and Gardnerella vaginalis vaginal loads associated with preterm birth?"
            ]
        },
        {
            "id": "task847-6f0c4549e0b44494bcff6efd1013c70c",
            "input": "Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), is an aggressive type of lymphoma whose standard treatment and validated prognostic model have not yet been defined.', 'CD30 expression was detected using immunohistochemistry in 96 ENKTL patients, and the data were used to evaluate its relationship with clinical features, treatment response and prognosis.', 'Expression of CD30 was detected in 31.2% of ENKTL patients, which was significantly correlated with B symptoms and elevated serum lactate dehydrogenase. The complete remission rate was not significantly different between CD30-positive and negative groups. After a median follow-up time of 31 months, 5-year overall survival (OS) and 5-year progression-free survival (PFS) rates in the CD30-positive group were both significantly lower than those in the CD30-negative group (34.1% vs. 64.4%, P=0.002, for 5 year-OS; 26.0% vs. 66.7%, P<0.001, for 5 year-PFS). In patients with an International Prognostic Index (IPI) or Korean Prognostic Index (KPI) score of 0-1, CD30 positivity was associated with shorter 5-year OS and PFS (IPI: P=0.001 and 0.002, respectively; KPI: P=0.018 and 0.023, respectively). In a multivariate Cox regression model, CD30 expression and stage were independent prognostic factors for OS (p=0.004 and p=0.012, respectively) and PFS (p=0.001 and p=0.022, respectively).",
            "output": [
                "Is cD30 expression a novel prognostic indicator in extranodal natural killer/T-cell lymphoma , nasal type?"
            ]
        },
        {
            "id": "task847-c5a833a11bdc4787a4198699dc931ce2",
            "input": "To observe the therapeutic effects of continuous plasma filtration absorption (CPFA) treatment on burn sepsis.', \"Thirty burn patients with sepsis hospitalized in Beijing Fengtai You'anmen Hospital from July 2009 to October 2012 were treated by CPFA for twice besides routine treatment. The blood samples were collected at five sites (A, B, C, D, and E, respectively) of blood purification equipment before and after CPFA, before and after hemoabsorption, and before hemofiltration. The plasma levels of TNF-\u03b1, IL-1\u03b2, IL-6, IL-10, interleukin-1 receptor antagonist (IL-1RA), soluble tumor necrosis factor receptor (sTNFR) I , and sTNFR-II from sites A, C, and E were determined with ELISA before CPFA was performed for the first time, and those from sites B and D were determined with ELISA after CPFA was performed for the first time. Plasma levels of the above-mentioned cytokines from sites A and B were determined with ELISA before CPFA and after CPFA was performed for the second time. The data of plasma levels of IL-1\u03b2P3, IL-1RA, sTNFR-I, sTNFR-II, and TNF-\u03b1 before CPFA and after CPFA was performed for the second time were collected for calculation of the ratios of IL-1RA to IL-1\u03b2 and sTNFR-I plus sTNFR-II to TNF-\u03b1. The expression rate of human leukocyte antigen DR (HLA-DR) on the CD14 positive monocytes, acute physiology and chronic health evaluation (APACHE) II score, body temperature, pulse, respiratory rate, and leukocyte count of patients were evaluated or recorded before CPFA and after CPFA was performed for the second time. Patients'condition was observed. Data were processed with paired t test.\", 'The plasma levels of TNF-\u03b1, IL-1\u03b2, IL-6 and IL-10 from site B after CPFA was performed for the second time were significantly lower than those from site A before CPFA was performed for the first time (with t values respectively 7.05, 5.23, 4.73, 2.37, P values below 0.01). After CPFA was performed for the first time, the plasma levels of TNF-\u03b1, IL-1\u03b2, and IL-6 from site D were significantly lower than those from site C before CPFA was performed for the first time (with t values respectively 5.48, 2. 17, 1.78, P < 0.05 or P <0.01). The plasma levels of all cytokines were close between site B after CPFA was performed for the first time and site E before CPFA was performed for the first time (with t values from 0.04 to 1.05, P values above 0.05). The plasma levels of TNF-\u03b1, IL-1\u03b2, and IL-6 from site B after CPFA was performed for the second time were significantly lower than those from site A before CPFA was performed for the second time (with t values from 1.87 to 5.93, P <0.05 or P <0.01). The ratios of IL-1RA to IL-1\u03b2 and sTNFR-I plus sTNFR-II to TNF-\u03b1, and expression rate of HLA-DR were increased significantly after CPFA was performed for the second time as compared with those before CPFA (with t values from 3.99 to 7. 80, P values below 0.01). APACHE II score after CPFA was performed for the second time was 11 \u00b1 6, which was lower than that before CPFA (22 \u00b1 7, t =4.63, P <0.01). After CPFA was performed for the second time, body temperature, pulse, and respiratory rate of patients were improved (with t values from 1.95 to 3.55, P values below 0.05) , and the leukocyte count was significantly decreased (t =4.36, P <0.01) as compared with those before CPFA. All patients survived and were discharged with length of stay of (27 \u00b1 31) d, and no adverse effects occurred during CPFA treatment.",
            "output": [
                "Do [ Clinical study on continuous plasma filtration absorption treatment for burn sepsis ]?"
            ]
        },
        {
            "id": "task847-13cb92ba83394328a025ac4206dc515e",
            "input": "Studies performed in Andean populations living in high altitude, indicate that the reduced availability of oxygen could be associated to both a fetal growth retardation and a lower birth weight. These variables are predictive of morbidity and mortality during the first year of life.', 'To study perinatal variables of newborns of mothers living at contrasting altitudinal levels, harboring different degrees of Aymara ancestry.', 'Review of medical records of 5,295 women whose deliveries occurred between February 2004 and August 2010. Information was obtained on place of residence, grouped into two categories: coast (150 to 3,000 m) and high plateau (3,000 to 4,300 m), ancestry was estimated using number of Aymara surnames that were homologated to percentages of Amerindian admixture, gestational age, birth weight, height, head circumference and obstetric variables.', 'Gestational age showed a tendency to increase and birth weight, height and head circumference to decrease with altitude of residence. Only weight reached statistical significance. Women with Aymara ancestry gave birth to children with a significantly higher gestational age, weight and cranial circumference.",
            "output": [
                "Do [ Perinatal variables from newborns of Aymara mothers suggest a genetic adaptation to high altitude ]?"
            ]
        },
        {
            "id": "task847-32d6a5bf5db34149af941457d62b8095",
            "input": "The aim of this study was to determine the association between 25-hydroxyvitamin D (25(OH)D) and neuroimaging correlates of cerebral small vessel disease.', 'We identified 759 consecutive patients with acute ischemic stroke or transient ischemic attack. Lacunes, white matter hyperintensity, and cerebral microbleed (CMB) were assessed using MR images. Deep CMB was defined as the presence of CMB in basal ganglia, thalamus, or brain stem. The association between 25(OH)D and small vessel disease was tested using linear and logistic regression analyses.', 'Mean age was 68 (\u00b113) years. Mean level of 25(OH)D was 34.1\u00b117.8 nmol/L. On bivariate analysis, a 25-nmol/L decrease in 25(OH)D was associated with lacunes (regression coefficient, 0.23; 95% confidence interval [CI], 0.02-0.45), severe white matter hyperintensity (odds ratio, 2.05; 95% CI, 1.41-3.08), and deep CMB (odds ratio, 1.28; 95% CI, 1.01-1.63). Also, 25(OH)D deficiency (\u226425 nmol/L) was associated with lacunes (regression coefficient, 0.5; 95% CI, 0.04-0.95), severe white matter hyperintensity (odds ratio, 2.74; 95% CI, 1.31-6.45), and deep CMB (odds ratio, 1.68; 95% CI, 1.03-2.78). The association remained significant even after multivariable adjustment and in the subgroup of previously healthy patients.",
            "output": [
                "Is 25-hydroxyvitamin D status associated with chronic cerebral small vessel disease?"
            ]
        },
        {
            "id": "task847-149bdfbe94ed4cfe9c5251640484c93b",
            "input": "The aims of this study were to demonstrate the tumorigenicity of CD133+ colon cancer cells in vitro, analyze the correlations between spheroid formation and clinicopathologic variables, and screen for overexpressed genes in CD133+ colon cancer stem cells. Moreover, the aim of this study was to establish a living tumor tissue bank using surgically resected specimens.', 'Using LoVo cell line, we isolated CD133+ cells and performed clonogenic assay and animal experiment to test tumorigenicity of CD133+ cells. Twenty-nine surgical samples were freshly collected from 27 patients who received curative or palliative surgery, and the samples were mechanically and enzymatically dissociated into single cells.', 'We confirmed the enhanced tumorigenicity of CD133+ cells isolated from LoVo cell line both in vitro and in vivo. Of these 29 samples, 8 (28%) contained >3% CD133+ cells. Sphere formation was significantly higher in samples from patients with lymphatic invasion than in those without lymphatic invasion [54.5% (6/11) vs. 12.5% (2/16); P=0.033] and in samples containing >3% of CD133+ cells than in those containing \u22643% of CD133+ cells [36.4% (4/11) vs. 0% (0/16); P=0.019].",
            "output": [
                "Is cD133-positive tumor cell content a predictor of early recurrence in colorectal cancer?"
            ]
        },
        {
            "id": "task847-97220b266cce4dcba3288b2112fea35d",
            "input": "Traumatic brain injury (TBI) affects millions of people each year and is characterized by direct tissue injury followed by a neuroinflammatory response. The post-TBI recovery period can be associated with a negative emotional state characterized by alterations in affective behaviors implicated in the development of Alcohol Use Disorder in humans. The aim of this study was to test the hypothesis that post-TBI neuroinflammation is associated with behavioral dysfunction, including escalated alcohol intake.', 'Adult male Wistar rats were trained to self-administer alcohol prior to counterbalanced assignment into na\u00efve, craniotomy, and TBI groups by baseline drinking. TBI was produced by lateral fluid percussion (LFP; >2 ATM; 25ms). Alcohol drinking and neurobehavioral function were measured at baseline and following TBI in all experimental groups. Markers of neuroinflammation (GFAP and ED1) and neurodegeneration (FJC) were determined by fluorescence histochemistry in brains excised at sacrifice 19 days post-TBI.', 'The cumulative increase in alcohol intake over the 15 days post-TBI was greater in TBI animals compared to na\u00efve controls. A higher rate of pre-injury alcohol intake was associated with a greater increase in post-injury alcohol intake in both TBI and craniotomy animals. Immediately following TBI, both TBI and craniotomy animals exhibited greater neurobehavioral dysfunction compared to na\u00efve animals. GFAP, IBA-1, ED1, and FJC immunoreactivity at 19 days post-TBI was significantly higher in brains from TBI animals compared to both craniotomy and na\u00efve animals.",
            "output": [
                "Does traumatic brain injury induce neuroinflammation and neuronal degeneration that is associated with escalated alcohol self-administration in rats?"
            ]
        },
        {
            "id": "task847-b0d035ed4e9149dfbe2e1403cea17f78",
            "input": "To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring.', 'Animal (rat) study.', 'Research laboratory.', 'Female Sprague-Dawley rats.', 'Food restriction during the second half of pregnancy in rats.', 'Circulating gonadotropins, antim\u00fcllerian hormone (AMH), ovarian morphology, estrous cyclicity, and gene expression studies in the hypothalamus and ovary in 1-day-old (P1) and aging adult offspring.', 'Offspring of MUN dams had low birth weight (LBW) and by adult age developed obesity. In addition, 80% of adult LBW offspring had disruption of estrous cycle by 8 months of age, with the majority of animals in persistent estrous. Ovarian morphology was consistent with acyclicity, with ovaries exhibiting large cystic structures and reduced corpora lutea. There was an elevation in circulating T, increased ovarian expression of enzymes involved in androgen synthesis, an increase in plasma LH/FSH levels, a reduction in E2 levels, and no changes in AMH in adult LBW offspring compared with in control offspring. Hypothalamic expression of leptin receptor (ObRb), estrogen receptor-\u03b1 (ER-\u03b1), and GnRH protein was altered in an age-dependent manner with increased ObRb and ER-\u03b1 expression in P1 LBW hypothalami and a reversal of this expression pattern in adult LBW hypothalami.",
            "output": [
                "Does maternal undernutrition induce premature reproductive senescence in adult female rat offspring?"
            ]
        },
        {
            "id": "task847-112a5607a17247dca44b7d7fea03cb9a",
            "input": "To determine whether granulocyte colony-stimulating factor (G-CSF) could prevent loss of spermatogenesis induced by busulfan chemotherapy via protection of undifferentiated spermatogonia, which might serve as an adjuvant approach to preserving male fertility among cancer patients.', 'Laboratory animal study.', 'University.', 'Laboratory mice.', 'Five-week-old mice were treated with a sterilizing busulfan dose and with 7 days of G-CSF or vehicle treatment and evaluated 10 weeks later (experiment 1) or 24 hours after treatment (experiment 2).', 'Experiment 1: testis weights, epididymal sperm counts, testis histology. Experiment 2: PLZF immunofluorescent costaining with apoptotic markers. Molecular analysis of G-CSF receptor expression in undifferentiated spermatogonia.', 'Ten weeks after treatment, busulfan-treated mice that also received treatment with G-CSF exhibited significantly better recovery of spermatogenesis and epididymal sperm counts than animals receiving busulfan alone. G-CSF led to increased numbers of PLZF+ spermatogonia 24 hours after treatment that was not accompanied by changes in apoptosis. To address the cellular target of G-CSF, mRNA for the G-CSF receptor, Csf3r, was found in adult mouse testes and cultured THY1+ (undifferentiated) spermatogonia, and cell-surface localized CSF3R was observed on 3% of cultured THY1+ spermatogonia.",
            "output": [
                "Does granulocyte colony-stimulating factor prevent loss of spermatogenesis after sterilizing busulfan chemotherapy?"
            ]
        },
        {
            "id": "task847-c89db4ada64a4cf7af9ce36e12d47750",
            "input": "A vaccine against hepatitis C virus (HCV) is unavailable and cost-effective antivirals that prevent HCV infection and re-infection, such as in the transplant setting, do not exist. In a search for novel and economical prophylactic agents, we examined the antiviral activity of saikosaponins (SSa, SSb2, SSc, and SSd) from Bupleurum kaoi root (BK) as entry inhibitors against HCV infection.', 'Infectious HCV culture systems were used to examine the effect of saikosaponins on the complete virus life cycle (entry, RNA replication/translation, and particle production). Antiviral activity against various HCV genotypes, clinical isolates, and infection of primary human hepatocytes were also evaluated.', 'BK and the saikosaponins potently inhibited HCV infection at non-cytotoxic concentrations. These natural agents targeted early steps of the viral life cycle, while leaving replication/translation, egress, and spread relatively unaffected. In particular, we identified SSb2 as an efficient inhibitor of early HCV entry, including neutralization of virus particles, preventing viral attachment, and inhibiting viral entry/fusion. Binding analysis, using soluble viral glycoproteins, demonstrated that SSb2 acted on HCV E2. Moreover, SSb2 inhibited infection by several genotypic strains and prevented binding of serum-derived HCV onto hepatoma cells. Finally, treatment with the compound blocked HCV infection of primary human hepatocytes.",
            "output": [
                "Is saikosaponin b2 a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry?"
            ]
        },
        {
            "id": "task847-e6e06ac8e61246df8f72ae579383f21a",
            "input": "Intrahepatic cholestasis of pregnancy (ICP) is defined by pruritus, elevated total fasting serum bile salts (TBS) and transaminases, and an increased risk of adverse fetal outcome. An accurate diagnostic marker is needed. Increased serum autotaxin correlates with cholestasis-associated pruritus. We aimed at unraveling the diagnostic accuracy of autotaxin in ICP.', 'Serum samples and placental tissue were collected from 44 women with uncomplicated pregnancies and 105 with pruritus and/or elevated serum transaminases. Autotaxin serum levels were quantified enzymatically and by Western blotting, autotaxin gene expression by quantitative PCR.', 'Serum autotaxin was increased in ICP (mean \u00b1 SD: 43.5 \u00b1 18.2 nmol ml(-1)min(-1), n=55, p<0.0001) compared to other pruritic disorders of pregnancy (16.8 \u00b1 6.7 nmol ml(-1)min(-1), n=33), pre-eclampsia complicated by HELLP-syndrome (16.8 \u00b1 8.9 nmol ml(-1)min(-1), n=17), and pregnant controls (19.6 \u00b1 5.7 nmol ml(-1)min(-1), n=44). Longitudinal analysis during pregnancy revealed a marked rise in serum autotaxin with onset of ICP-related pruritus. Serum autotaxin was increased in women taking oral contraceptives. Increased serum autotaxin during ICP was not associated with increased autotaxin mRNA in placenta. With a cut-off value of 27.0 nmol ml(-1)min(-1), autotaxin had an excellent sensitivity and specificity in distinguishing ICP from other pruritic disorders or pre-eclampsia/HELLP-syndrome. Serum autotaxin displayed no circadian rhythm and was not influenced by food intake.",
            "output": [
                "Does autotaxin activity have a high accuracy to diagnose intrahepatic cholestasis of pregnancy?"
            ]
        },
        {
            "id": "task847-19cc234e3b5948e98df5c9a28abf91c7",
            "input": "Programs seek to expose trainees to research during residency. However, little is known in any formal sense regarding how to do this effectively, or whether these efforts result in more or better-quality research output.', 'The objective of our study was to evaluate a dedicated resident research program in terms of the quantity and quality of resident research peer-reviewed publications. Specifically we asked: (1) Did residents mentored through a dedicated resident research program have more peer-reviewed publications in higher-impact journals with higher citation rates compared with residents who pursued research projects under a less structured approach? (2) Did this effect continue after graduation?', 'In 2006, our department of orthopaedic surgery established a dedicated resident research program, which consisted of a new research policy and a research committee to monitor quality and compliance with this policy. Peer-reviewed publications (determined from PubMed) of residents who graduated 6 years before establishing the dedicated resident research program were compared with publications from an equal period of the research-program-directed residents. The data were assessed using descriptive statistics and regression analysis. Twenty-four residents graduated from 2001 to 2006 (before implementation of the dedicated resident research program); 27 graduated from 2007 to 2012 (after implementation of the dedicated resident research program). There were 74 eligible publications as defined by the study inclusion and exclusion criteria.', \"Residents who trained after implementation of the dedicated resident research program published more papers during residency than did residents who trained before the program was implemented (1.15 versus 0.79 publications per resident; 95% CI [0.05,0.93]; p = 0.047) and the journal impact factor was greater in the group that had the research program (1.25 versus 0.55 per resident; 95% CI [0.2,1.18]; p = 0.005). There were no differences between postresidency publications by trainees who graduated with versus without the research program in the number of publications, citations, and average journal impact factor per resident. A regression analysis showed no difference in citation rates of the residents' published papers before and since implementation of the research program.",
            "output": [
                "Does a dedicated research program increase the quantity and quality of orthopaedic resident publications?"
            ]
        },
        {
            "id": "task847-cb704718195e4477809487942810b7b1",
            "input": "Heterotopic ossification (HO) may occur after musculoskeletal trauma, traumatic brain injury, and total joint arthroplasty. As such, HO is a compelling clinical concern in both military and civilian medicine. A possible etiology of HO involves dysregulated signals in the bone morphogenetic protein osteogenic cascade. Contemporary treatment options for HO (ie, nonsteroidal antiinflammatory drugs and radiation therapy) have adverse effects associated with their use and are not biologically engineered to abrogate the molecular mechanisms that govern osteogenic differentiation.', 'We hypothesized that (1) nanogel-mediated short interfering RNA (siRNA) delivery against Runt-related transcription factor 2 (Runx2) and osterix (Osx) genes will decrease messenger RNA expression; (2) inhibit activity of the osteogenic marker alkaline phosphatase (ALP); and (3) inhibit hydroxyapatite (HA) deposition in osteoblast cell cultures.', 'Nanogel nanostructured polymers delivered siRNA in 48-hour treatment cycles against master osteogenic regulators, Runx2 and Osx, in murine calvarial preosteoblasts (MC3T3-E1.4) stimulated for osteogenic differentiation by recombinant human bone morphogenetic protein (rhBMP-2). The efficacy of RNA interference (RNAi) therapeutics was determined by quantitation of messenger RNA knockdown (by quantitative reverse transcription-polymerase chain reaction), downstream protein knockdown (determined ALP enzymatic activity assay), and HA deposition (determined by OsteoImage\u2122 assay).', 'Gene expression assays demonstrated that nanogel-based RNAi treatments at 1:1 and 5:1 nanogel:short interfering RNA weight ratios reduced Runx2 expression by 48.59%\\xa0\u00b1\\xa019.53% (p\\xa0<\\xa00.001) and 43.22%\\xa0\u00b1\\xa018.01% (both p\\xa0<\\xa00.001). The same 1:1 and 5:1 treatments against both Runx2 and Osx reduced expression of Osx by 51.65%\\xa0\u00b1\\xa010.85% and 47.65%\\xa0\u00b1\\xa09.80% (both p\\xa0<\\xa00.001). Moreover, repeated 48-hour RNAi treatment cycles against Runx2 and Osx rhBMP-2 administration reduced ALP activity after 4 and 7\\xa0days. ALP reductions after 4\\xa0days in culture by nanogel 5:1 and 10:1 RNAi treatments were 32.4%\\xa0\u00b1\\xa012.0% and 33.6%\\xa0\u00b1\\xa013.8% (both p\\xa0<\\xa00.001). After 7\\xa0days in culture, nanogel 1:1 and 5:1 RNAi treatments produced 35.9%\\xa0\u00b1\\xa014.0% and 47.7%\\xa0\u00b1\\xa03.2% reductions in ALP activity. Osteoblast mineralization data after 21\\xa0days suggested that nanogel 1:1, 5:1, and 10:1 RNAi treatments decreased mineralization (ie, HA deposition) from cultures treated only with rhBMP-2 (p\\xa0<\\xa00.001). However, despite RNAi attack on Runx2 and Osx, HA deposition levels remained greater than non-rhBMP-2-treated cell cultures.",
            "output": [
                "Does cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery decrease Mineralization in MC3T3 Cells?"
            ]
        },
        {
            "id": "task847-d7aa8c57351b4001a26576736ca5588d",
            "input": "Restoration of posterior condylar offset during TKA is believed to be important to improving knee kinematics, maximizing ROM, and minimizing flexion instability. However, controversy exists regarding whether there are important anatomic differences between sexes and whether a unisex knee prosthesis can restore the anatomy of knees in males and females.', 'The purposes of our study were to determine if sex differences exist in (1) absolute posterior condylar offset size, (2) relative posterior condylar offset size in relation to total condylar height, and (3) posterior condylar articular cartilage thickness.', 'We identified 100 patients (50 men and 50 women) without a history of arthritis, deformity, dysplasia, osteochondral defect, fracture, or surgery about the knee who had MRI of the knee performed. All MR images were ordered by primary care medical physicians for evaluation of nonspecific knee pain. Using a previously described three-dimensional MRI protocol, we measured posterior condylar offset, total condylar height, and articular cartilage thickness at the medial and lateral femoral condyles and compared values to evaluate for potential sex differences. We performed an a priori power calculation using a 2-mm posterior condylar offset difference as the minimum clinically important difference; with 2n = 100, our power to detect such a difference was 99.8%.', 'Compared with females, males had greater medial posterior condylar offset (30 mm [95% CI, 29.3-30.7 mm; SD, 2.5 mm] vs 28 mm [95% CI, 27.0-28.5 mm; SD, 2.7 mm]), lateral posterior condylar offset (27 mm [95% CI, 26.2-27.3 mm; SD, 2.0 mm] vs 25 mm [95% CI, 24.2-25.4 mm; SD, 2.0 mm]), medial condylar height (63 mm [SD, 3.2 mm] vs 57 mm [SD, 4.4 mm]), and lateral condylar height (71 mm [SD, 5.2 mm] vs 65 mm [SD: 4.0 mm]) (all p values < 0.001). However, the mean ratio of medial posterior condylar offset to medial condylar height (0.48 [SD, 0.04] vs 0.49 [SD, 0.05]) and the mean ratio of lateral posterior condylar offset to lateral condylar height (0.38 [SD, 0.05] vs 0.38 [SD, 0.03]) were not different between sexes (p = 0.08 and p = 0.8, respectively). There also was no sex difference in mean articular cartilage thickness at either condyle (medial condyle: 2.7 mm [SD, 0.5 mm] vs 2.5 mm [SD, 0.7 mm]; lateral condyle: 2.6 mm [SD, 0.6 mm] vs 2.5 mm [SD, 0.8 mm]) (both p values \u2265 0.1).",
            "output": [
                "Do no sex differences exist in posterior condylar offsets of the knee?"
            ]
        },
        {
            "id": "task847-20397b2a4bd9496db80768d830d32587",
            "input": "We sought to identify whether stable single nucleotide polymorphisms (SNPs) of various endocrine and immune molecules could be used as biomarkers associated with specific immune alterations and chronic stress measures in normal humans.', 'A total of 207 volunteer participants answered stress questionnaire and gave peripheral blood cells for identification of SNPs in genes coding for glucocorticoid receptor (GR), beta 2 adrenergic receptor (B2AR), interferon-gamma receptors (IFNGR1, IFNGR2), and interleukin-4 receptor (IL4R). Immunoregulatory profiles were measured by flow cytometry and genotyping assays were performed by allelic discrimination real-time PCR.', 'Several significant differences were revealed in associations between stress marker and immune indicators based on SNP categories. For instance, Th1 levels of the minor alleles of GR TthIIII (AA) and IFNGR2 Q64R (Arg/Arg) groups were positively associated with chronic stress (PSS) (p = 0.024 and 0.005, respectively) compared with wild type (WT) and negatively associated with PSS in the heterozygous genotypes of GR BclI and IL4R Ile50Val (p = 0.040 and p = 0.052, respectively). Treg levels of the minor alleles of BclI (GG) and IFNGR1 T-56C (CC) groups were positively associated with PSS (p = 0.045 and p = 0.010, respectively) and negatively associated in the minor allele (Val/Val) of IL4R Ile50Va and the heterozygous genotype of IL4R Q576R (p = 0.041 and p = 0.017, respectively) compared to WT.",
            "output": [
                "Do gene polymorphisms of stress hormone and cytokine receptors associate with immunomodulatory profile and psychological measurement?"
            ]
        },
        {
            "id": "task847-a2da89f079fa4e5fb1c301e509e2a2f2",
            "input": "Researchers studying the murine response to stress generally use mice housed under standard, nationally mandated conditions as controls. Few investigators are concerned whether basic physical aspects of mouse housing could be an additional source of stress, capable of influencing the subsequent impact of an experimentally applied stressor. We have recently become aware of the potential for housing conditions to impact important physiological and immunological properties in mice.', 'Here we sought to determine whether housing mice at standard temperature (ST; 22\\u2009\u00b0C) vs. thermoneutral temperature (TT; 30\\u2009\u00b0C) influences baseline expression of heat shock proteins (HSPs) and their typical induction following a whole body heating.', 'There were no significant differences in baseline expression of HSPs at ST and TT. However, in several cases, the induction of Hsp70, Hsp110 and Hsp90 in tissues of mice maintained at ST was greater than at TT following 6\\u2009h of heating (which elevated core body temperature to 39.5\\u2009\u00b0C). This loss of HSP induction was also seen when mice housed at ST were treated with propranolol, a \u03b2-adrenergic receptor antagonist, used clinically to treat hypertension and stress.",
            "output": [
                "Does housing temperature influence the pattern of heat shock protein induction in mice following mild whole body hyperthermia?"
            ]
        },
        {
            "id": "task847-f8d465dcaf214fa4afe387df6c636bae",
            "input": "The important functions of the meniscus are shock absorption, passive stabilization and load transmission of the knee. Because of the avascularity of two-thirds of the meniscal center region, the treatment of tears in this area is hard. Recently, microRNAs have been proven to play an important role in the pathogenesis of diseases. We focused on microRNA (miR)-210, which plays a wide spectrum of roles comprising mitochondrial metabolism, angiogenesis, DNA repair and cell survival. This study aimed to investigate the effect of intra-articular injection of synthetic miR-210 on the injured meniscus in the avascular zone.', 'The middle segments of the medial meniscus of Spraque Dawley rats were incised longitudinally with a scalpel. An intra-articular injection of double-stranded (ds) miR-210 (for control group using control dsRNA) with atelocollagen was administered immediately after injury. Four weeks and 12\\xa0weeks after the injection, we conducted a histologic evaluation, immunohistochemical evaluation and Real-time PCR analysis. In vitro, the inner meniscus and synovial cells were isolated from rat knee joint, and were transfected with ds miR-210 or control dsRNA. Real-time PCR and immunohistochemical evaluations were performed.', 'Twenty-four hours after the injection, FAM (Fluorescein amidite) labeled miR-210 was observed in the cells around the injured site. Four weeks after the injection, the injured site of the miR-210 group was filled with repaired tissue while that of the control was not repaired. In gene expression analysis of the meniscus, the expression of miR-210, Collagen type 2 alpha 1 (Col2a1), Vascular endothelial growth factor (VEGF), and Fibroblast growth factor-2 (FGF2) in the miR-210 group was significantly higher than that in the control. At 12\\xa0weeks, the intra-articular injection of miR-210 had healed the injured site of the meniscus and had prevented articular cartilage degeneration. In vitro, miR-210 upregulated Col2a1 expression in the meniscus cells and VEGF and FGF2 expression in the synovial cells.",
            "output": [
                "Does intra-articular injection of synthetic microRNA-210 accelerate avascular meniscal healing in rat medial meniscal injured model?"
            ]
        },
        {
            "id": "task847-b24926e35f544844a2e6db74dd3ec1fa",
            "input": "Protein arginine methyltransferase 5 (PRMT5), is thought to play a role in epigenetic reprogramming of mouse germ cells. However, up to now there has been little information concerning its expression profile and effects on generation of induced pluripotent stem cells (iPSCs) from somatic cells, in livestock. Here, we have explored PRMT5 expression profiles in dairy goats and its consequences to derivation of iPSCs from dairy goat embryonic fibroblasts (GEFs).', 'We investigated effects of PRMT5 on iPS-like cells production in vitro. alkaline phosphatase (AP) staining, QRT-PCR and western blotting analysis of expression of related markers were used to evaluate efficiency of generation of iPSCs derived from GEFs.', 'These showed PRMT5 to be a conservative gene widely expressed in various tissues and different-aged testes. PRMT5 overexpression in combination with OCT3/4, SOX2, KLF4 and C-MYC (POSKM) significantly increased number of AP positive iPS-like colony-derived GEFs compared to OSKM alone, in our dairy goats. Moreover, our results demonstrated that PRMT5 overexpression stimulated GEF proliferation and down-regulated p53, p21 (a target gene of p53) and the apoptotic marker caspase 3, to enhance somatic cell reprogramming.",
            "output": [
                "Does pRMT5 enhance generation of induced pluripotent stem cells from dairy goat embryonic fibroblasts via down-regulation of p53?"
            ]
        },
        {
            "id": "task847-bd0db5b056a14f5e980dd9f493b32aba",
            "input": "Minimally invasive retroperitoneoscopic surgery (MIS) for psoas abscess (PA) in patients with thoracolumbar tuberculosis is not well-illustrated and has not reached the status of being fully clinically assessed when we review the English literatures. The aim of this study is to introduce and investigate on efficacy and feasibility of MIS (retroperitoneoscopic technique) for PA in patients with thoracolumbar tuberculosis.', 'From January 2008 to 2013, 39 consecutive patients of the diagnosis of PA with thoracolumbar tuberculosis received the debridement of abscesses and cavity walls of abscesses by the retroperitoneoscopic technique (MIS) in combination with anti-tuberculosis chemotherapy. Medical records and follow-up data were retrospectively studied. CRP and ESR of every patient preoperatively and postoperatively were analyzed', 'Immediate relief in clinical symptoms and signs, and amelioration in imaging and laboratory examinations were obviously observed in all the patients. The follow-up had proceeded for 12-48 (mean 23) months. No complication was observed during the follow-up postoperatively.",
            "output": [
                "Do minimally invasive retroperitoneoscopic surgery for psoas abscess with thoracolumbar tuberculosis?"
            ]
        },
        {
            "id": "task847-6920015931ed4da88dbfc584f004d301",
            "input": "To evaluate the thickness of cartilage at the posterior aspect of the medial and lateral condyle in Osteoarthritis (OA) knees compared to non-OA knees using computed tomography arthrography (CTA).', '535 consecutive knee CTAs (mean patient age = 48.7 \u00b1 16.0; 286 males), were retrospectively analyzed. Knees were radiographically classified into OA or non-OA knees according to a modified Kellgren/Lawrence (K/L) grading scheme. Cartilage thickness at the posterior aspect of the medial and lateral femoral condyles was measured on sagittal reformations, and compared between matched OA and non-OA knees in the whole sample population and in subgroups defined by gender and age.', 'The cartilage of the posterior aspect of medial condyle was statistically significantly thicker in OA knees (2.43 mm (95% confidence interval (CI) = 2.36, 2.51)) compared to non-OA knees (2.13 mm (95%CI = 2.02, 2.17)) in the entire sample population (P < 0.001), as well as for all subgroups of patients over 40 years old (all P \u2264 0.01), except for females above 60 years old (P = 0.07). Increase in cartilage thickness at the posterior aspect of the medial condyle was associated with increasing K/L grade in the entire sample population, as well as for males and females separately (regression coefficient = 0.10-0.12, all P < 0.001). For the lateral condyle, there was no statistically significant association between cartilage thickness and OA (either presence of OA or K/L grade).",
            "output": [
                "Is cartilage thickness at the posterior medial femoral condyle increased in femorotibial knee osteoarthritis : a cross-sectional CT arthrography study ( Part 2 )?"
            ]
        },
        {
            "id": "task847-d70c544d16184ed0a75561bfe7c6d558",
            "input": "To investigate the specific role of Frizzled-related protein (FRZB) and Secreted frizzled-related protein 1 (SFRP1) in the onset and progression of Osteoarthritis (OA) using Frzb(-/-) and Sfrp1(-/-) mice in the destabilization of medial meniscus model (DMM), a slowly progressing model of OA. Secreted frizzled-related proteins (SFRPs) were identified as secreted Wingless-type (Wnt) antagonists. The Wnt signaling cascade is a major regulator in cartilage development, homeostasis and degeneration.', 'The DMM model was surgically induced in eight-week-old male C57/Bl6 Frzb(-/-), Sfrp1(-/-) or wild-type mice by transection of the medial meniscotibial ligament. Cartilage damage in the femoral and tibial articular surfaces was calculated following the Osteoarthritis Research Society International (OARSI) histopathology initiative guidelines. Histomorphometry was used to evaluate the subchondral bone plate thickness.', 'OA severity scores were significantly higher in the tibia of Frzb(-/-) mice as compared to littermates, whereas no interaction was seen between genotype and intervention in Sfrp1(-/-) mice. Moreover, the DMM model resulted in significantly greater subchondral bone changes compared to sham but was not different between Frzb(-/-) mice and littermates. In contrast, the subchondral bone properties in Sfrp1(-/-) mice were significantly different from littermates.",
            "output": [
                "Does loss of Frzb and Sfrp1 differentially affect joint homeostasis in instability-induced osteoarthritis?"
            ]
        },
        {
            "id": "task847-ad4174d5e67c42ac8f93b12158107147",
            "input": "Recently, pluripotency of induced pluripotent stem (iPS) cells has been displayed after producing adult mice, in tetraploid complementation assays. These studies lead us to the last piece of the puzzle for reprogramming somatic cells into fully pluripotent cells which function as embryonic stem cells in most applications. However, in all of previous studies, skin fibroblasts were used as the starting population for reprogramming, raising questions as to whether the pluripotency of the iPS cells was dependent on the particular starting cell type.', 'Our iPS cell lines were prepared from murine adipose stem cells (ASCs). Their multi-potency was first tested by teratoma formation in nude mice. Then, tetraploid complementation was performed to generate progeny from them.', 'We succeeded to the birth of viable and fertile adult mice derived entirely from reprogrammed ASC, indicating cell types other than fibroblasts can also be restored to the embryonic level of pluripotency.",
            "output": [
                "Does tetraploid complementation prove pluripotency of induced pluripotent stem cells derived from adipose tissue?"
            ]
        },
        {
            "id": "task847-f2590139196d47ff8f7b6dfa6c1d8181",
            "input": "Several reports have indicated the benefits of the acute care surgery (ACS) model in surgical outcomes. We tried to delineate the impact of the ACS model on surgical efficiency and quality.', 'Before the ACS model was implemented, abdominal surgical emergencies were evaluated by an on-call nontrauma general surgeon (pre-ACS model). An in-house trauma surgeon treated all patients with trauma or nontrauma abdominal surgical emergencies after the ACS model. Patients with acute appendicitis who underwent appendectomies were included. We conducted a pre- and poststudy to compare the time patients were in the emergency department and surgical qualities.', 'There were 146 and 159 patients enrolled in the pre-ACS model and ACS model, respectively. The overall ED length of stay in the ACS model was significantly shorter than that in the pre-ACS model (300.3 \u00b1 61.7 vs 719.1 \u00b1 339.0 minutes, P < .001). Hospital LOS was also significantly shorter in the ACS model than in the pre-ACS model (2.44 \u00b1 1.39 vs 3.83 \u00b1 2.21 days, P = .022).",
            "output": [
                "Does implementation of the acute care surgery model provide benefits in the surgical treatment of the acute appendicitis?"
            ]
        },
        {
            "id": "task847-6d7e0983314049069dfd8a23f2b16f5b",
            "input": "Most hepatocellular carcinomas (HCCs) are associated with cirrhosis. Portal hypertension (PHT) and esophageal variceal bleeding (EVB) can limit the patient's treatment options. Surgical therapy in such patients is challenging. We performed devascularization plus liver resection or radiofrequency ablation (RFA) to treat HCC patients with concomitant EVB resulting from PHT secondary to cirrhosis. Such combined operations have never been reported for the management of HCC patients with variceal esophageal bleeding.\", 'To evaluate two different treatment regimens for patients with HCC and EVB.', 'We evaluated 35 BCLC stage 0/A patients with HCC and EVB who underwent either devascularization plus liver resection (Group A) or devascularization plus RFA (Group B). We reviewed the safety and outcomes of the two groups and assessed risk factors for patient survival and tumor recurrence.', 'Significant factors for overall survival were surgical approach and Child-Pugh classification. Child-Pugh classification was the only independent risk factor for overall postoperative survival [hazard ratio (HR) 8.320, 95 % confidence interval (CI) 1.739-39.799, P = 0.008]. Age was the only independent risk factor for tumor recurrence (HR 4.025, 95 % CI 1.343-12.062, P = 0.013).",
            "output": [
                "Is radiofrequency ablation plus devascularization the preferred treatment of hepatocellular carcinoma with esophageal varices?"
            ]
        },
        {
            "id": "task847-c238bf90126e46b89cee061e6ffed4ab",
            "input": "Assessment of the activity of thioridazine towards Mycobacterium tuberculosis (Mtb), in\\xa0vitro and in\\xa0vivo as a single drug and in combination with tuberculosis (TB) drugs.', 'The in\\xa0vitro activity of thioridazine as single drug or in combination with TB drugs was assessed in terms of MIC and by use of the time-kill kinetics assay. Various Mtb strains among which the Beijing genotype strain BE-1585 were included. In\\xa0vivo, mice with TB induced by BE-1585 were treated with a TB drug regimen with thioridazine during 13 weeks. Therapeutic efficacy was assessed by the change in mycobacterial load in the lung, spleen and liver during treatment and 13 weeks post-treatment.', 'In\\xa0vitro, thioridazine showed a concentration-dependent and time-dependent bactericidal activity towards both actively-replicating and slowly-replicating Mtb. Thioridazine at high concentrations could enhance the activity of isoniazid and rifampicin, and in case of isoniazid resulted in elimination of mycobacteria and prevention of isoniazid-resistant mutants. Thioridazine had no added value in combination with moxifloxacin or amikacin. In mice with TB, thioridazine was poorly tolerated, limiting the maximum tolerated dose (MTD). The addition of thioridazine at the MTD to an isoniazid-rifampicin-pyrazinamide regimen for 13 weeks did not result in enhanced therapeutic efficacy.",
            "output": [
                "Is enhancement of in vitro activity of tuberculosis drugs by addition of thioridazine reflected by improved in vivo therapeutic efficacy?"
            ]
        },
        {
            "id": "task847-b82a231e77e048c1a5a9600f4e7a3e9b",
            "input": "The prevalence of obesity in children is high, and many do not meet physical activity recommendations. The Safe Routes to School (SRTS) program encourages school-aged children to walk and bike to school. We assessed the condition of the walking/biking environment around schools in Louisiana prior to the state's first SRTS program.\", \"Assessments were made at the neighborhood level with the Pedestrian Environmental Data Scan (PEDS) instrument, and at the school and individual levels using the National SRTS Center's teacher tallies and parent surveys. PEDS scores were developed to rate conduciveness to walking/bicycling of proposed SRTS routes. Sites' scores were compared with the percentage of students who walk/bike to school. Five schools in Louisiana were evaluated.\", 'Overall, more students walked (range: 2.4-17.4%) than biked (range: 0.3-4.5%) to school with more students walking home than to school. Predictors of walking/biking to school include distance from school, speed of traffic, school encouragement, and if a student asked permission. Sites with the highest PEDS score had the highest percentage of students who walked/biked to school.",
            "output": [
                "Do youth walking and biking rates vary by environments around 5 Louisiana schools?"
            ]
        },
        {
            "id": "task847-7cf4d2ac785c445ebece73f126ea114f",
            "input": "Stroke is the third leading cause of invalidism and death in industrialized countries. There are conflicting reports about the effects of Angiotensin II on ischemia-reperfusion brain injuries and most data have come from chronic hypertensive rats. In this study, hypotensive and non-hypotensive doses of candesartan were used to investigate the effects of angiotensin II AT1 receptor blockade by transient focal cerebral ischemia in normotensive rats.', 'In this experimental study, 48 male Sprague-Dawley rats were randomly divided into four groups (n=12). Sham group, the control ischemic group, and two ischemic groups received candesartan at doses of 0.1 or 0.5 mg/kg at one hour before ischemia. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 h reperfusion. The neurological deficit score was evaluated at the end of the reperfusion period. The total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride staining technique. Tissue swelling was calculated for the investigation of ischemic brain edema formation.', 'In comparison with the control ischemic group, AT1 receptor blockade with both doses of candesartan (0.1 or 0.5 mg/kg) significantly improved neurological deficit and lowered cortical and striatal infarct sizes. In addition, pretreatment with candesartan significantly reduced ischemia induced tissue swelling.",
            "output": [
                "Does blockade of Central Angiotensin II AT1 Receptor protect the Brain from Ischemia/Reperfusion Injury in Normotensive Rats?"
            ]
        },
        {
            "id": "task847-57e443e0f89147e5b4a21ead817ca863",
            "input": "Genetic haploinsufficiency of SYNGAP1/Syngap1 commonly occurs in developmental brain disorders, such as intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder. Thus, studying mouse models of Syngap1 haploinsufficiency may uncover pathologic developmental processes common among distinct brain disorders.', 'A Syngap1 haploinsufficiency model was used to explore the relationship between critical period dendritic spine abnormalities, cortical circuit assembly, and the window for genetic rescue to understand how damaging mutations disrupt key substrates of mouse brain development.', 'Syngap1 mutations broadly disrupted a developmentally sensitive period that corresponded to the period of heightened postnatal cortical synaptogenesis. Pathogenic Syngap1 mutations caused a coordinated acceleration of dendrite elongation and spine morphogenesis and pruning of these structures in neonatal cortical pyramidal neurons. These mutations also prevented a form of developmental structural plasticity associated with experience-dependent reorganization of brain circuits. Consistent with these findings, Syngap1 mutant mice displayed an altered pattern of long-distance synaptic inputs into a cortical area important for cognition. Interestingly, the ability to genetically improve the behavioral endophenotype of Syngap1 mice decreased slowly over postnatal development and mapped onto the developmental period of coordinated dendritic insults.",
            "output": [
                "Does syngap1 haploinsufficiency damage a postnatal critical period of pyramidal cell structural maturation linked to cortical circuit assembly?"
            ]
        },
        {
            "id": "task847-f284c45b20e6492aa039ec75590808bb",
            "input": "Immunologic abnormalities have been found in bipolar disorder but pentraxin 3, a marker of innate immunity, has not been studied in this population.', 'Levels of pentraxin 3 were measured in individuals with bipolar disorder, schizophrenia, and non-psychiatric controls. Linear regression models were used to compare the pentraxin 3 levels in each of the psychiatric groups to that in the control group, adjusting for demographic and clinical variables. Logistic regression models were used to calculate the odds ratios associated with levels of pentraxin 3 which differed from specified levels of the control group.', 'The sample consisted of 831 individuals: 256 with bipolar disorder, 309 with schizophrenia, and 266 without a psychiatric disorder. The levels of pentraxin 3 in the bipolar disorder, but not in the schizophrenia, group were significantly lower than those of controls, adjusting for age, gender, race, maternal education, smoking status, and body mass index (t = -3.78, p < 0.001). The individuals with bipolar disorder also had significantly increased odds of having low levels of pentraxin 3 relative to both the 10th and 25th percentile level of the controls and significantly decreased odds of having a level greater than the 75th and the 90th percentile level of the controls, adjusting for the same covariates.",
            "output": [
                "Is pentraxin 3 reduced in bipolar disorder?"
            ]
        },
        {
            "id": "task847-c48d2cfe56e64e8bbe92e94f9f36e183",
            "input": "Convulsions associated with fever and acute onset of unknown aetiology with case fatalities have become a long observed medical condition at the Child Health Department of the Korle-Bu Teaching Hospital. Children admitted to the department with seizures of undetermined origin and fever has been a source of diagnostic confusion. Studies from the Asia Pacific region suggest a link with non-polio enteroviruses. The aim of the study was to investigate the association between non-polio enterovirus and acute encephalopathy causing neurological morbidity in children.', 'One hundred and fifty cerebrospinal fluid (CSF), throat swab and serum samples were collected from participants at the Child Health Department of the Korle-Bu Teaching Hospital for virus isolation and characterization. Samples were cultured on cells and positive culture assayed by microneutralisation. Direct PCR as well as multiplex PCR were used to detect other viral agents present.', 'Enterovirus isolation rate was approximately 0.67%. Intratypic differentiation by molecular characterization identified a poliovirus from vaccine origin. Further screening by real-time RT-PCR identified the virus as normal Sabin and not vaccine-derive poliovirus. No arbovirus was however detected.",
            "output": [
                "Are human enteroviruses the cause of neurological impairments in children at the Korle-Bu Teaching Hospital?"
            ]
        },
        {
            "id": "task847-ff261550b704468fa9dfee421e465bc7",
            "input": "Ex vivo heart perfusion (EVHP) provides the opportunity to resuscitate unused donor organs and facilitates assessments of myocardial function that are required to demonstrate organ viability before transplantation. We sought to evaluate the effect of different oxygen carriers on the preservation of myocardial function during EVHP.', 'Twenty-seven pig hearts were perfused ex vivo in a normothermic beating state for 6 hours and transitioned into working mode for assessments after 1 (T1), 3 (T3), and 5 (T5) hours. Hearts were allocated to 4 groups according to the perfusate composition. Red blood cell concentrate (RBC, n = 6), whole blood (RBC+Plasma, n = 6), an acellular hemoglobin-based oxygen carrier (HBOC, n = 8), or HBOC plus plasma (HBOC+Plasma, n = 7) were added to STEEN Solution (XVIVO Perfusion, Goteborg, Sweden) to achieve a perfusate hemoglobin concentration of 40 g/liter.', 'The perfusate composition affected the preservation of systolic (T5 dP/dtmax: RBC+Plasma = 903 \u00b1 99, RBC = 771 \u00b1 77, HBOC+Plasma = 691 \u00b1 82, HBOC = 563 \u00b1 52 mm Hg/sec; p = 0.047) and diastolic (T5 dP/dtmin: RBC+Plasma = -574 \u00b1 48, RBC = -492 \u00b1 63, HBOC+Plasma = -326 \u00b1 32, HBOC = -268 \u00b1 22 mm Hg/sec; p < 0.001) function, and the development of myocardial edema (weight gain: RBC+Plasma = 6.6 \u00b1 0.9, RBC = 6.6 \u00b1 1.2, HBOC+Plasma = 9.8 \u00b1 1.7, HBOC = 16.3 \u00b1 1.9 g/hour; p < 0.001) during EVHP. RBC+Plasma hearts exhibited less histologic evidence of myocyte damage (injury score: RBC+Plasma = 0.0 \u00b1 0.0, RBC = 0.8 \u00b1 0.3, HBOC+Plasma = 2.6 \u00b1 0.2, HBOC = 1.75 \u00b1 0.4; p < 0.001) and less troponin-I release (troponin-I fold-change T1-T5: RBC+Plasma = 7.0 \u00b1 1.7, RBC = 13.1 \u00b1 1.6, HBOC+Plasma = 20.5 \u00b1 1.1, HBOC = 16.7 \u00b1 5.8; p < 0.001). Oxidative stress was minimized by the addition of plasma to RBC and HBOC hearts (oxidized phosphatidylcholine compound fold-change T1-T5: RBC+Plasma = 1.83 \u00b1 0.20 vs RBC = 2.31 \u00b1 0.20, p < 0.001; HBOC+Plasma = 1.23 \u00b1 0.17 vs HBOC = 2.80 \u00b1 0.28, p < 0.001).",
            "output": [
                "Does a whole blood-based perfusate provide superior preservation of myocardial function during ex vivo heart perfusion?"
            ]
        },
        {
            "id": "task847-9e91868ec2a14643aa65be337462284d",
            "input": "Immune monitoring (IM) has not been shown to be associated with cardiac allograft vasculopathy (CAV).', 'Maximal intimal area, average percent stenosis, plaque volume, and maximal intimal thickness (MIT) were measured for matched baseline and one-yr IVUS segments in a blinded fashion. Patients were divided into quartiles by IM scores and outcomes compared. Optimal IM cutoff was determined.', 'IM assays were measured at 63.7 \u00b1 16.4 d after transplantation in fifty patients. Progression of maximal intimal area (p = 0.005), average percent stenosis (p < 0.001), plaque volume (p = 0.005), and MIT (p = 0.001) were increased across the quartiles. An optimal IM assay cutoff of 406.0 ng ATP/mL demonstrated a sensitivity of 66.7% and specificity of 94.3% for predicting rapid progression of MIT \u2265 0.5 mm. Mean IM scores for Group 1 vs. Group 2 were 176.4 \u00b1 102.2 and 616.3 \u00b1 239.5 ngATP/mL, respectively. Rapid progression of MIT \u2265 0.5 mm occurred in 5/38 patients (13.2%) in Group 1 vs. 10/12 patients (83.3%) in Group 2 (p < 0.001). The risk ratio for rapid progression with elevated IM was 11.7 (p < 0.001).",
            "output": [
                "Is elevated immune monitoring early after cardiac transplantation associated with increased plaque progression by intravascular ultrasound?"
            ]
        },
        {
            "id": "task847-d254c4b959554baa825457a31699e8b3",
            "input": "Poultry remains a major source of foodborne bacterial infections. A variety of additives with presumed anti-microbial and/or growth-promoting effects are commonly added to poultry feed during commercial grow-out, yet the effects of these additives on the gastrointestinal microbial community (the GI microbiome) as the bird matures remain largely unknown. Here we compared temporal changes in the cecal microbiome to the effects of formic acid, propionic acid, and medium-chain fatty acids (MCFA) added to feed and/or drinking water.', 'Cecal bacterial communities at day of hatch (n\\u2009=\\u20095 birds), 7d (n\\u2009=\\u200932), 21d (n\\u2009=\\u200927), and 42d (n\\u2009=\\u200936) post-hatch were surveyed using direct 454 sequencing of 16S rRNA gene amplicons from each bird in combination with cultivation-based recovery of a Salmonella Typhimurium marker strain and quantitative-PCR targeting Clostridium perfringens. Treatment effects on specific pathogens were generally non-significant. S. Typhimurium introduced by oral gavage at day of hatch was recovered by cultivation from nearly all birds sampled across treatments at 7d and 21d, but by 42d, S. Typhimurium was only recovered from ca. 25% of birds, regardless of treatment. Sequencing data also revealed non-significant treatment effects on genera containing known pathogens and on the cecal microbiome as a whole. In contrast, temporal changes in the cecal microbiome were dramatic, highly significant, and consistent across treatments. At 7d, the cecal community was dominated by three genera (Flavonifractor, Pseudoflavonifractor, and a Lachnospiracea sequence type) that accounted for more than half of sequences. By 21d post-hatch, a single genus (Faecalibacterium) accounted for 23-55% of sequences, and the number of Clostridium 16S rRNA gene copies detected by quantitative-PCR reached a maximum.",
            "output": [
                "Are successional changes in the chicken cecal microbiome during 42 days of growth independent of organic acid feed additives?"
            ]
        },
        {
            "id": "task847-0fe5f8cc8050481d859adfbd866461c2",
            "input": "Palmitate, a saturated fatty acid (FA), is known to induce toxicity and cell death in various types of cells. Resveratrol (RSV) is able to prevent pathogenesis and/or decelerate the progression of a variety of diseases. Several in vitro and in vivo studies have also shown a protective effect of RSV on fat accumulation induced by FAs. Additionally, endoplasmic reticulum (ER) stress has recently been linked to cellular adipogenic responses. To address the hypothesis that the RSV effect on excessive fat accumulation promoted by elevated saturated FAs could be partially mediated by a reduction of ER stress, we studied the RSV action on experimentally induced ER stress using palmitate in several cancer cell lines.', 'We show that, unexpectedly, RSV promotes an amplification of palmitate toxicity and cell death and that this mechanism is likely due to a perturbation of palmitate accumulation in the triglyceride form and to a less important membrane fluidity variation. Additionally, RSV decreases radical oxygen species (ROS) generation in palmitate-treated cells but leads to enhanced X-box binding protein-1 (XBP1) splicing and C/EBP homologous protein (CHOP) expression. These molecular effects are induced simultaneously to caspase-3 cleavage, suggesting that RSV promotes palmitate lipoapoptosis primarily through an ER stress-dependent mechanism. Moreover, the lipotoxicity reversion induced by eicosapentaenoic acid (EPA) or by a liver X receptor (LXR) agonist reinforces the hypothesis that RSV-mediated inhibition of palmitate channeling into triglyceride pools could be a key factor in the aggravation of palmitate-induced cytotoxicity.",
            "output": [
                "Does resveratrol enhance palmitate-induced ER stress and apoptosis in cancer cells?"
            ]
        },
        {
            "id": "task847-d9dfd0960bf74736b82c87e5897cbc3e",
            "input": "In renal cell carcinoma (RCC), the prediction of metastasis via tumor prognostic markers remains a major problem. The objective of our study was to evaluate the efficacy of cyclin-dependent kinase (CDK)1 and CDK2 activity as a prognostic marker in human RCC.', 'Surgical specimens were obtained from 125 patients with RCC without metastasis. Protein expression and kinase activity of CDKs were analyzed using a newly developed assay system named C2P (Sysmex, Kobe, Japan). We then examined the specific activities (SAs) of CDK1 and CDK2 and calculated CDK2SA-CDK1SA ratio in RCC. Also, risk score (RS) was examined.', 'A total of 125 cases were tested, though 34 cases were excluded because of low sample quality (25 cases) and assay failure (9 cases). In total, 91 cases were analyzed. They included 68 male and 23 female patients, ranging in age from 19 to 83 years. At a median follow-up of 36 months (1-109M), tumor with low CDK2SA-CDK1SA ratio showed significantly better 5-year recurrence-free survival than those with high CDK2SA-CDK1SA ratio (88.7% vs. 54.7%, P = 0.00141). Also, RS enabled the classification of RCCs into high-risk and low-risk groups, and patients with tumors classified as low RS showed better recurrence-free survival than patients with tumors with high RS (88.7% vs. 54.7%, P = 0.0141).",
            "output": [
                "Is cDK1 and CDK2 activity a strong predictor of renal cell carcinoma recurrence?"
            ]
        },
        {
            "id": "task847-3f523c02c41d4533b24e7879dcefa02b",
            "input": "To compare optic nerve head (ONH) morphology between eyes with normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG).', 'Seventy-eight NTG patients and 78 POAG patients matched according to age and axial length were analyzed. Optic nerve head tilt and torsion were identified from cross-sectional images of optical coherence tomography. The degree of horizontal, vertical, and maximum ONH tilt and torsion was compared between NTG and POAG eyes, and additional comparisons were based on the presence of myopia and the location of the visual field defect. Logistic regression analysis was used to determine the factors related to the degree of ONH torsion.', 'Vertical (P = 0.610) and horizontal tilt degree (P = 0.746) did not differ between NTG and POAG eyes. However, torsion degree (P = 0.022) differed significantly between NTG and POAG eyes. Direction of vertical tilt (P = 0.040) and torsion (P < 0.001) showed more prevalent superior tilt and torsion in NTG eyes (21.8% and 33.3%, respectively) compared to POAG eyes (10.3% and 10.3%, respectively). Myopic NTG eyes showed greater torsion degree (P = 0.014) than nonmyopic NTG eyes, which was not observed in the comparison between myopic and nonmyopic POAG eyes. Only NTG eyes showed a significant difference in the degree of maximum tilt (P < 0.001) and torsion (P < 0.001) and the direction of vertical tilt (P < 0.001) and torsion (P = 0.010) by the location of visual field defect. Longer axial length, maximum tilt degree, and diagnosis of NTG were the factors related to the degree of ONH torsion.",
            "output": [
                "Is torsion of the optic nerve head a prominent feature of normal-tension glaucoma?"
            ]
        },
        {
            "id": "task847-ac74efbd3884458b82559e6b478220c6",
            "input": "The aims of this study were to determine the effect of failed prior endovascular treatment (EV) on early and midterm outcomes of subsequent lower extremity open surgical (OS) bypass.', 'Patients undergoing infrainguinal bypass for critical limb ischemia (CLI) from January 2008 to December 2011 were retrospectively reviewed. The results after first-line bypass and bypass after failure of EV treatment were compared. A total of 213 patients (65.25% men; average age, 73.30 years) underwent bypass. OS patients were then divided into 2 groups: group 1 consisted of 138 patients who underwent primary OS for CLI without prior EV (control group) and group 2 consisted of 75 patients who had OS after a failed attempt at elective EV for peripheral vascular disease. Of the 213 bypass performed, 34% had a prior infrainguinal failed EV. The primary study end points were early and 1-year major amputations and graft occlusion. The secondary outcomes included early and 1-year mortality and the level of distal revascularization.', 'Secondary patency and limb salvage rates were significantly better in group 1 up to 1 year (99% vs. 86%; P < 0.001 at 1 month and 95% vs. 76%, P < 0.05 at 12 months, respectively).",
            "output": [
                "Is endo first appropriate in some patients with critical limb ischemia because `` bridges are burned ''?"
            ]
        },
        {
            "id": "task847-5287224ad98a43adacb001722515e35a",
            "input": "Guillotine below-knee amputation (BKA) for wet gangrene is an unfortunate complication of poorly controlled diabetes. We examined risk factors associated with wound complications after amputation formalization in this patient population.', 'Retrospective data over a 4-year period were collected for patients undergoing guillotine BKA for wet gangrene followed by staged formalization. Patients with abnormal distal pulses underwent evaluation before formalization to stratify for peripheral arterial disease (PAD). Those patients with palpable pulses and no known PAD went to formalization without further investigation. Poor operative candidates underwent delayed formalization to allow for preoperative optimization. Patient history, interval between surgeries, pathology, and preformalization laboratories were tested for significance. Primary outcome was postformalization wound complication.', 'Fifty-six amputations in 55 patients met inclusion criteria. Wound complications after formalization occurred in 18 cases, all BKAs (32%). A history of PAD was present in 19 patients (34.5%). On pathology, 23 patients (41%) had small-vessel atherosclerosis or arteriosclerosis. There was no association between wound complications and history of PAD (P = 0.4), preformalization albumin (P = 0.09), glucose (P = 0.9), white blood cell count (P = 0.4), or delayed versus expedited formalization (P = 0.8). Only the presence of microvascular disease on formal pathology was predictive of wound complications (P = 0.03). There was no association between microvascular disease on pathology and a history of PAD (P = 0.07).",
            "output": [
                "Is unrecognized arteriosclerosis associated with wound complications after below-knee amputation?"
            ]
        },
        {
            "id": "task847-45434317398f48959f62a7a1b0089dbc",
            "input": "Remote renal ischemia-reperfusion injury (IRI) following infra-renal aortic occlusion leads to acute kidney injury and systemic inflammation. Hydrogen sulfide is a mediator of IRI and can ameliorate tissue injury in many organ systems. Its role in vascular surgery has yet to be established. We assessed the role of hydrogen sulfide in a rodent model of aortic occlusion.', 'Wistar rats were divided into sham, control, and treatment groups (n = 6). Inflammation was assessed using a nonrecovery protocol. The infra-renal aorta was cross-clamped for 60 min and animals were reperfused for 120 min. Ten minutes before clamp release, treatment animals received hydrogen sulfide (10, 30, or 50 \u03bcg/kg) and control animals received 0.9% saline injected into the retroperitoneum. Renal injury and histology were assessed by a recovery protocol. The procedure was identical to the nonrecovery arm but with a single dose of hydrogen sulfide (30 \u03bcg/kg) and animals were recovered for 7 days.', 'There was no difference in animal weight between the groups (P = 0.337). In the nonrecovery arm, there was a reduction in serum levels of tumor necrosis factor alpha in sulfide-treated animals compared with controls (909 \u00b1 98 vs. 607 \u00b1 159 pg/mL; P = 0.0038). There was also a reduction in myeloperoxidase-positive cells in renal tissue in the sulfide-treated animals compared with controls (8 \u00b1 4 vs. 17 \u00b1 9; P = 0.03). There was no difference in histological injury score or endothelin-1 levels. In the recovery arm, there was no difference in renal function, Kidney Injury Molecule-1 levels, or histological injury scores.",
            "output": [
                "Does hydrogen sulfide reduce inflammation following abdominal aortic occlusion in rats?"
            ]
        },
        {
            "id": "task847-bd647387c93542f6a081843739f30b6a",
            "input": "Gene flow from crops to their wild relatives has the potential to alter population growth rates and demography of hybrid populations, especially when a new crop has been genetically modified (GM). This study introduces a comprehensive approach to assess this potential for altered population fitness, and uses a combination of demographic data in two habitat types and mathematical (matrix) models that include crop rotations and outcrossing between parental species.', 'Full life-cycle demographic rates, including seed bank survival, of non-GM Brassica rapa\\u2009\u00d7\\u2009B. napus F1 hybrids and their parent species were estimated from experiments in both agricultural and semi-natural habitats. Altered fitness potential was modelled using periodic matrices including crop rotations and outcrossing between parent species.', 'The demographic vital rates (i.e. for major stage transitions) of the hybrid population were intermediate between or lower than both parental species. The population growth rate (\u03bb) of hybrids indicated decreases in both habitat types, and in a semi-natural habitat hybrids became extinct at two sites. Elasticity analyses indicated that seed bank survival was the greatest contributor to \u03bb. In agricultural habitats, hybrid populations were projected to decline, but with persistence times up to 20 years. The seed bank survival rate was the main driver determining persistence. It was found that \u03bb of the hybrids was largely determined by parental seed bank survival and subsequent replenishment of the hybrid population through outcrossing of B. rapa with B. napus.",
            "output": [
                "Do seed bank dynamics govern persistence of Brassica hybrids in crop and natural habitats?"
            ]
        },
        {
            "id": "task847-d55970ad9e7440e8b9924069e220f21e",
            "input": "Progression from actinic keratosis (AK) to invasive squamous cell carcinoma (iSCC) of the skin is thought to occur after the development of full thickness epidermal neoplasia, as in the classic pathway of cervical cancer. Nevertheless, cutaneous iSCC may also directly arise from a proliferation of atypical basaloid cells limited mostly to the epidermal basal layer (AK I), akin to what happens in the 'differentiated pathway' of iSCC of the vulva, oral cavity and other locations.\", 'To evaluate the prevalence of classic and differentiated pathways in the development of cutaneous iSCC.', 'The epidermis adjacent to and overlying iSCC, assumed to be representative of pre-existing lesions, was histologically studied in 196 skin biopsy specimens showing iSCC.', 'AK I, AK II and AK III lesions overlying iSCC were present in 63.8%, 17.9% and 18.4% of cases respectively. The corresponding percentages in the epidermis adjacent to iSCC were 77.9%, 6.6% and 8.3% respectively (stage could not be assessed in 8.1% of cases). Focal epidermal ulceration overlying iSCC was seen in 32% of AK I, 28.6% of AK II and 33.3% of AK III instances. Adnexal involvement by atypical keratinocytes (proliferative AK) was present more frequently in cases with overlying AK I (39/125, 31.2%) than with AK II (8/35, 22.9%) and AKII I (5/36, 13.9%).",
            "output": [
                "Is actinic keratosis with atypical basal cells ( AK I ) the most common lesion associated with invasive squamous cell carcinoma of the skin?"
            ]
        },
        {
            "id": "task847-259c6a5554da41e89e681e9e1ab10643",
            "input": "Ascent to high altitude leads to a reduction in ambient pressure and a subsequent fall in available oxygen. The resulting hypoxia can lead to elevated pulmonary artery (PA) pressure, capillary stress, and an increase in interstitial fluid. This fluid can be assessed on lung ultrasound (LUS) by the presence of B-lines. We undertook a chamber and field study to assess the impact of high-intensity exercise in hypoxia on the development of pulmonary interstitial edema in healthy lowlanders.', 'Thirteen volunteers completed a high-intensity intermittent exercise (HIIE) test at sea level, in acute normobaric hypoxia (12% O2, approximately 4090 m equivalent altitude), and in hypobaric hypoxia during a field study at 4090 m after 6 days of acclimatization. Pulmonary interstitial edema was assessed by the evaluation of LUS B-lines.', 'After HIIE, no increase in B-lines was seen in normoxia, and a small increase was seen in acute normobaric hypoxia (2 \u00b1 2; P < .05). During the field study at 4090 m, 12 participants (92%) demonstrated 7 \u00b1 4 B-lines at rest, which increased to 17 \u00b1 5 immediately after the exercise test (P < .001). An increase was evident in all participants. There was a reciprocal fall in peripheral arterial oxygen saturations (Spo2) after exercise from 88% \u00b1 4% to 80% \u00b1 8% (P < .01). B-lines and Spo2 in all participants returned to baseline levels within 4 hours.",
            "output": [
                "Does high-intensity intermittent exercise increase pulmonary interstitial edema at altitude but not at simulated altitude?"
            ]
        },
        {
            "id": "task847-bf4d190230a5462dabcd217c2e5871cc",
            "input": "To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction.', 'Prospective cohort study.', 'A minority cohort in New York City previously recruited for a trial of telemedicine.', 'Persons aged 73.0 \u00b1 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black).', 'Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction.', 'Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction.",
            "output": [
                "Does mild cognitive dysfunction affect diabetes mellitus control in minority elderly adults?"
            ]
        },
        {
            "id": "task847-66750d9c6cd7415a95f1a0066b4b8a05",
            "input": "To investigate whether serum anti-high mobility group box 1 (anti-HMGB1) antibodies are related to the development of skin lesions in systemic lupus erythematosus (SLE).', 'This study involved 21 SLE patients with skin lesions, 18 without skin lesions, and 22 healthy controls. The presence and serum levels of anti-HMGB1-IgG and -IgM were measured by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. HMGB1 expression and serum antibodies deposited in the skin were visualized by immunofluorescence staining.', 'Using western blot analysis, we detected anti-HMGB1-IgG antibodies in 13 out of 21 SLE patients with skin lesions and 11 out of 18 SLE patients without skin lesions (p > 0.05). Serum levels of anti-HMGB1-IgG measured by ELISA were also comparable between the two groups of SLE patients (p > 0.05) but were higher in patients than in healthy controls (p < 0.05). Similar results were found with serum anti-HMGB1-IgM antibodies. HMGB1 accumulated under the stratum corneum in lupus cutaneous lesions without forming immune complexes with IgG or IgM, which were mainly observed along the epidermal-dermal junction. Furthermore, serum anti-HMGB1-IgM was higher in the group of patients with arthritis than in those without arthritis.",
            "output": [
                "Are anti-high mobility group box 1 ( anti-HMGB1 ) antibodies related to the occurrence of cutaneous lesions in systemic lupus erythematosus?"
            ]
        },
        {
            "id": "task847-5bebf15fb66e474385e1a15c3b3661b8",
            "input": "Excessive consumption of ethanol is one of the most common causes of acute and chronic pancreatitis. Alterations to the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) also cause pancreatitis. However, little is known about the role of CFTR in the pathogenesis of alcohol-induced pancreatitis.', 'We measured CFTR activity based on chloride concentrations in sweat from patients with cystic fibrosis, patients admitted to the emergency department because of excessive alcohol consumption, and healthy volunteers. We measured CFTR levels and localization in pancreatic tissues and in patients with acute or chronic pancreatitis induced by alcohol. We studied the effects of ethanol, fatty acids, and fatty acid ethyl esters on secretion of pancreatic fluid and HCO3(-), levels and function of CFTR, and exchange of Cl(-) for HCO3(-) in pancreatic cell lines as well as in tissues from guinea pigs and CFTR knockout mice after administration of alcohol.', \"Chloride concentrations increased in sweat samples from patients who acutely abused alcohol but not in samples from healthy volunteers, indicating that alcohol affects CFTR function. Pancreatic tissues from patients with acute or chronic pancreatitis had lower levels of CFTR than tissues from healthy volunteers. Alcohol and fatty acids inhibited secretion of fluid and HCO3(-), as well as CFTR activity, in pancreatic ductal epithelial cells. These effects were mediated by sustained increases in concentrations of intracellular calcium and adenosine 3',5'-cyclic monophosphate, depletion of adenosine triphosphate, and depolarization of mitochondrial membranes. In pancreatic cell lines and pancreatic tissues of mice and guinea pigs, administration of ethanol reduced expression of CFTR messenger RNA, reduced the stability of CFTR at the cell surface, and disrupted folding of CFTR at the endoplasmic reticulum. CFTR knockout mice given ethanol or fatty acids developed more severe pancreatitis than mice not given ethanol or fatty acids.",
            "output": [
                "Does alcohol disrupt levels and function of the cystic fibrosis transmembrane conductance regulator to promote development of pancreatitis?"
            ]
        },
        {
            "id": "task847-8d594ee62cb04066b482faf1c701e9d3",
            "input": "Flow-mediated dilation (FMD) is a complex mechanism involving several mediators, and different hemodynamic forces. Temporally distinct FMD patterns can be elicited by ischemic stimulus. Some subjects dilate early after cuff release, while others dilate later or do not dilate at all. Aim of the present research was to verify if hemorheological and hemodynamic factors might influence different FMD pattern.', '148 free-living subjects were studied. FMD was measured at 50 s, 2 min and 3 min. Blood viscosity was measured and shear stress calculated. Shear stress stimulus was quantified as the area under the curve after ischemia (SSAUC) over the first 40-s post-occlusion.', 'Based on the timing or absence of arterial dilation, 82 subjects were classified as Early dilators, 37 as Late dilators and 29 as No dilators. Peak FMD was 7.9 \u00b1 4.3 % in Early dilators, and 9.1 \u00b1 5.7 in Late dilators (p = NS). SSAUC was not significantly different among three groups, while blood viscosity was significantly higher in Late FMD subjects. Regression analyses showed the independent predictive role of age and blood viscosity on FMD patterns, and the lack of any association between FMD pattern and the magnitude of SS.",
            "output": [
                "Does blood viscosity but not shear stress associate with delayed flow-mediated dilation?"
            ]
        },
        {
            "id": "task847-36bfdc7869ad44c78e782f788d4c4fc2",
            "input": "Neutrophils can synthesize leukotriene B4 (LTB4) by activating the 5-lipoxygenase (5-LO)signaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils.', 'Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, M\u03b2CD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059.",
            "output": [
                "Does hypercholesterolemia increase the production of leukotriene B4 in neutrophils by enhancing the nuclear localization of 5-lipoxygenase?"
            ]
        },
        {
            "id": "task847-1bc496beb25e4cbe9bf5b6dfe6223ab0",
            "input": "The purpose of this study was to address the affects of mood modifying drugs on the transcriptome, in a tissue culture model, using qPCR arrays as a cost effective approach to identifying regulatory networks and pathways that might coordinate the cell response to a specific drug.', 'We addressed the gene expression profile of 90 plus genes associated with human mood disorders using the StellARray\u2122 qPCR gene expression system in the human derived SH-SY5Y neuroblastoma cell line.', 'Global Pattern Recognition (GPR) analysis identified a total of 9 genes (DRD3(\u204e), FOS(\u2020), JUN(\u204e), GAD1(\u204e\u2020), NRG1(\u204e), PAFAH1B3(\u204e), PER3(\u204e), RELN(\u204e) and RGS4(\u204e)) to be significantly regulated in response to cellular challenge with the mood stabilisers sodium valproate ((\u204e)) and lithium ((\u2020)). Modulation of FOS and JUN highlights the importance of the activator protein 1 (AP-1) transcription factor pathway in the cell response. Enrichment analysis of transcriptional networks relating to this gene set also identified the transcription factor neuron restrictive silencing factor (NRSF) and the oestrogen receptor as an important regulatory mechanism.",
            "output": [
                "Do molecular signatures of mood stabilisers highlight the role of the transcription factor REST/NRSF?"
            ]
        },
        {
            "id": "task847-d162b83b73104dcfb3c618bf520d5b23",
            "input": "Skeletal myoblasts fuse to form functional syncytial myotubes as an integral part of the skeletal muscle. During this differentiation process, expression of proteins for mechanical and electrical integration is seized, which is a major drawback for the application of skeletal myoblasts in cardiac regenerative cell therapy, because global heart function depends on intercellular communication.', 'Mechanically preconditioned engineered tissue constructs containing neonatal mouse skeletal myoblasts were transplanted epicardially. A Y-chromosomal specific polymerase chain reaction (PCR) was undertaken up to 10 weeks after transplantation to confirm the presence of grafted cells. Histologic and electrophysiologic analyses were carried out 1 week after transplantation.', 'Cells within the grafted construct expressed connexin 43 at the interface to the host myocardium, indicating electrical coupling, confirmed by sharp electrode recordings. Analyses of the maximum stimulation frequency (5.65 \u00b1 0.37 Hz), conduction velocity (0.087 \u00b1 0.011 m/s) and sensitivity for pharmacologic conduction block (0.736 \u00b1 0.080 mM 1-heptanol) revealed effective electrophysiologic coupling between graft and host cells, although significantly less robust than in native myocardial tissue (maximum stimulation frequency, 11.616 \u00b1 0.238 Hz, P\\xa0<\\xa0.001; conduction velocity, 0.300 \u00b1 0.057 m/s, P\\xa0<\\xa0.01; conduction block, 1.983 \u00b1 0.077 mM 1-heptanol, P\\xa0<\\xa0.001).",
            "output": [
                "Does preconditioning of skeletal myoblast-based engineered tissue constructs enable functional coupling to myocardium in vivo?"
            ]
        },
        {
            "id": "task847-e321d8da8b1840b29a04e0133d0a197b",
            "input": "Helminth-derived molecules are being identified as a new therapeutic approach for immune-mediated diseases. We investigated the anti-inflammatory effect and the immunological mechanisms of Schistosoma mansoni soluble egg antigens (SmSEA) in a mouse model of chronic colitis.', 'Colitis was induced in immunocompromised severe combined immunodeficiency mice by the adoptive transfer of CD4CD25CD62L T cells. Two weeks post-transfer, SmSEA treatments were started (study 1: 1 \u00d7 20 \u03bcg SmSEA per week 5 times; study 2: 2 \u00d7 20 \u03bcg SmSEA per week 3 times). From the start of the treatment (week 2), the clinical outcome and colonic inflammation were assessed at different time points by a clinical disease score and colonoscopy, respectively. At the end of the studies, the colons were harvested for macroscopic examination, and colonic lamina propria mononuclear cells were isolated for flow cytometric T-cell characterization.', 'In both studies, administration of SmSEA in colitis mice improved all the inflammatory parameters studied. However in study 1, this beneficial effect on inflammation diminished with time, and the T-cell characterization of the lamina propria mononuclear cells, performed at week 6, revealed no immunological effects of the SmSEA treatment. In study 2, mice were killed earlier (week 4) and at that time point, we found a significant downregulation of the number of interleukin-17A-producing T cells and a significant upregulation of the number of interleukin-4-producing T cells in the colon of the SmSEA-treated colitis mice.",
            "output": [
                "Does treatment with egg antigens of Schistosoma mansoni ameliorate experimental colitis in mice through a colonic T-cell-dependent mechanism?"
            ]
        },
        {
            "id": "task847-1f85127f44f6494485464819d88e0b57",
            "input": "The etiology of reduced left ventricular (LV) ejection fraction after exercise, without obstructive coronary artery disease or other established causes, is unclear. The aims of this study were to determine whether patients undergoing treadmill stress echocardiography with this abnormal LV contractile response to exercise (LVCRE) without established causes have resting LV long-axis dysfunction or microvascular dysfunction and to determine associations with this abnormal LVCRE.', 'Of 5,275 consecutive patients undergoing treadmill stress echocardiography, 1,134 underwent cardiac computed tomography angiography or invasive angiography. Having excluded patients with obstructive coronary artery disease, hypertensive response, submaximal heart rate response, resting LV ejection fraction < 50%, and valvular disease, 110 with \"abnormal LVCRE\" and 212 with \"normal LVCRE\" were analyzed. Resting mitral annular velocities were measured to assess LV long-axis function. Myocardial blush grade and corrected Thrombolysis In Myocardial Infarction frame count were determined angiographically to assess microvascular function.', \"Comparing normal LVCRE with abnormal LVCRE, age (mean, 59.7 \u00b1 11.1 vs 61.4 \u00b1 10.0 years), hypertension (53% vs 55%), diabetes (16% vs 20%), and body mass index (mean, 29.1 \u00b1 5.4 vs 29.5 \u00b1 6.4 kg/m(2)) were similar (P > .05). Abnormal LVCRE had reduced resting LV long-axis function with lower septal (mean, 6.1 \u00b1 1.9 vs 7.7 \u00b1 2.2 cm/sec) and lateral (mean, 8.1 \u00b1 2.9 vs 10.4 \u00b1 3.0 cm/sec) e' velocities (P < .001) and larger resting left atrial volumes (mean, 37.3 \u00b1 10.1 vs 31.1 \u00b1 7.2 mL/m(2), P < .001). On multivariate analysis, female gender (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.15-1.99; P < .001), exaggerated chronotropic response (OR, 1.49; 95% CI, 1.09-2.05; P < .001), resting left atrial volume (OR, 2.38; 95% CI, 1.63-3.47; P < .001), and resting lateral e' velocity (OR, 1.70; 95% CI, 1.22-2.49; P = .003) were associated with abnormal LVCRE, but not myocardial blush grade or corrected Thrombolysis In Myocardial Infarction frame count.",
            "output": [
                "Is abnormal left ventricular contractile response to exercise in the absence of obstructive coronary artery disease associated with resting left ventricular long-axis dysfunction?"
            ]
        },
        {
            "id": "task847-c7b5c5c575084c6f855ef1a4c4551e35",
            "input": "The objective of this study was to examine the associations between objective measures of sleep duration and sleep efficiency with the grades obtained by healthy typically developing children in math, language, science, and art while controlling for the potential confounding effects of socioeconomic status (SES), age, and gender.', \"We studied healthy typically developing children between 7 and 11 years of age. Sleep was assessed for five week nights using actigraphy, and parents provided their child's most recent report card.\", 'Higher sleep efficiency (but not sleep duration) was associated with better grades in math, English language, and French as a second language, above and beyond the contributions of age, gender, and SES.",
            "output": [
                "Is sleep efficiency ( but not sleep duration ) of healthy school-age children associated with grades in math and languages?"
            ]
        },
        {
            "id": "task847-d3403df830d84afea2388a395dfa5388",
            "input": "Morbidly obese patients usually present vitamin D deficiency or secondary hyperparathyroidism. Low vitamin D levels have been recently related to non-alcoholic fatty liver disease (NAFLD). The aim of this study was to analyse the relationship between vitamin D, bone turnover markers and non-alcoholic fatty liver disease and metabolic syndrome in severely obese patients.', 'One hundred and ten patients who underwent bariatric surgery were included. Liver biopsy was taken during surgery. Two univariate analyses were carried out in order to i) analyse the relationship between liver histology and vitamin D-bone turnover markers (intact parathyroid hormone (PTH), osteocalcin and Carboxy-terminal collagen crosslinks) and ii) establish the association between metabolic syndrome components-insulin resistance (HOMA) and vitamin D-bone turnover markers.', '70% of the patients had lower levels of vitamin D or secondary hyperparathyroidism. None of the components of liver histology were associated with levels of vitamin D or with bone turnover parameters. Patients with metabolic syndrome showed lower levels of PTH and osteocalcin (72,42 (29,47) vs 61.25(19.59) p-Value: 0.022; 19.79 (10.43) vs 16.87(10.25) p-Value: 0,028, respectively). HOMA was not related to Vitamin D or bone turnover markers.",
            "output": [
                "Are vitamin D levels and bone turnover markers related to non-alcoholic fatty liver disease in severely obese patients?"
            ]
        },
        {
            "id": "task847-da452e0899184e269b8238cd4aab13f9",
            "input": "The optimal type of mesh for complex abdominal wall reconstruction has not been elucidated. We hypothesized that AWRs using acellular dermal matrix (ADM) experience low rates of surgical site occurrence (SSO) and surgical site infection, despite increasing degrees of wound contamination.', 'We retrospectively reviewed prospectively collected data from consecutive abdominal wall reconstructions with ADM over a 9-year period. Outcomes of abdominal wall reconstructions were compared between patients with different CDC wound classifications. Univariate and multivariate logistic regression and Cox proportional hazard regression analyses identified potential associations and predictive/protective factors.', 'The 359 patients had a mean follow-up of 28.3 \u00b1 19.0 months. Reconstruction of clean wounds (n\\xa0= 171) required fewer reoperations than that of combined contaminated (n\\xa0=\\xa0188) wounds (2.3% vs 11.2%; p\\xa0= 0.001) and trended toward experiencing fewer SSOs (19.9% vs 28.7%, p\\xa0= 0.052). There were no significant differences between clean and combined contaminated cases in 30-day SSI (8.8% vs 8.0%), hernia recurrence (9.9% vs 10.1%), and mesh removal (1.2% vs 1.1%) rates. Independent predictors of SSO included body mass index \u226530 kg/m(2) (odds ratio [OR] 3.6; p < 0.001), 1 or more comorbidities (OR 2.5; p\\xa0= 0.008), and defect width \u226515 cm (OR 1.8; p\\xa0= 0.02).",
            "output": [
                "Are outcomes of abdominal wall reconstruction with acellular dermal matrix affected by wound contamination?"
            ]
        },
        {
            "id": "task847-191106c0eec54fc2b4d811370ad18e6b",
            "input": "Improper mechanical ventilation can exacerbate acute lung damage, causing a secondary ventilator-induced lung injury (VILI). We hypothesized that VILI can be reduced by modifying specific components of the ventilation waveform (mechanical breath), and we studied the impact of airway pressure release ventilation (APRV) and controlled mandatory ventilation (CMV) on the lung micro-anatomy (alveoli and conducting airways). The distribution of gas during inspiration and expiration and the strain generated during mechanical ventilation in the micro-anatomy (micro-strain) were calculated.', 'Rats were anesthetized, surgically prepared, and randomized into 1 uninjured control group (n\\xa0= 2) and 4 groups with lung injury: APRV 75% (n\\xa0= 2), time at expiration (TLow) set to terminate appropriately at 75% of peak expiratory flow rate (PEFR); APRV 10% (n\\xa0= 2), TLow set to terminate inappropriately at 10% of PEFR; CMV with PEEP 5 cm H2O (PEEP 5; n\\xa0= 2); or PEEP 16 cm H2O (PEEP 16; n\\xa0= 2). Lung injury was induced in the experimental groups by Tween lavage and ventilated with their respective settings. Lungs were fixed at peak inspiration and end expiration for standard histology. Conducting airway and alveolar air space areas were quantified and conducting airway micro-strain was calculated.', 'All lung injury groups redistributed inspired gas away from alveoli into the conducting airways. The APRV 75% minimized gas redistribution and micro-strain in the conducting airways and provided the alveolar air space occupancy most similar to control at both inspiration and expiration.",
            "output": [
                "Does airway pressure release ventilation reduce conducting airway micro-strain in lung injury?"
            ]
        },
        {
            "id": "task847-a3ea3b888e2240afa6008d5bc5964b29",
            "input": "To prevent accidental ingestion of implant hex dive.', \"Dental floss which is used to stabilize the hex drive is tied to the operator's finger ring to overcome sudden aspiration of fallen instrument.\", 'It showed excellent grip of the instrument during stage two uncover time and also saved operators time.",
            "output": [
                "Do a simplified method of preventing implant hex drive from aspiration or accidental swallowing during stage two implant recovery?"
            ]
        },
        {
            "id": "task847-e6330f4028eb4933b0e934994d9ac3d2",
            "input": "A study was undertaken to identify the responsible gene defect underlying late onset spinal motor neuronopathy (LOSMoN/SMAJ; Online Mendelian Inheritance in Man #615048), an autosomal dominant disease mapped to chromosome 22q11.2.', 'The previous genetic linkage approach by microsatellite haplotyping was continued in new families. A whole genome sequencing was performed to find all possibly pathogenic mutations in the linked area. The detected variations were verified by Sanger sequencing.', 'Six new SMAJ families were identified based on the unique founder haplotype. A critical recombination in 1 family restricted the linked area to 727kb between markers SHGC-106816 and D22S345. In whole genome sequencing a previously unknown mutation c.197G>T p.G66V in CHCHD10 was identified. The mutation was shown to segregate with the disease in 55 patients from 17 families.",
            "output": [
                "Is late onset spinal motor neuronopathy caused by mutation in CHCHD10?"
            ]
        },
        {
            "id": "task847-51e617d9761d403590a367a0df3433c2",
            "input": "In emergency cases, finger stick testing is primarily used to check the blood glucose value of patients since it takes longer to obtain the venous value. In critical patients, under conditions that cause an increase in metabolic state and level of stress, there occurs considerable difference in glucose levels between capillary and venous measurements. This study aimed to investigate the comparability of capillary and venous glucose values, according to the perfusion index level obtained with the Masimo Radical-7(\u00ae) device, in critical patients aged 18 years and over.', 'We conducted this prospective and observational study in the emergency department of the Eskisehir Osmangazi University hospital between November 3, 2008 and February 2, 2009.', 'The blood glucose of 300 critical patients was checked by finger stick in the emergency unit. The participants with normal vital signs had perfusion index between 0 and 5; the results obtained by the two methods were more consistent for perfusion index values of 6 and over. The results were most consistent in aged participants with normal vital sign findings and low perfusion index and in young patients with high perfusion index. In the cases where at least one of the vital signs was abnormal, the glucose values obtained by the two methods were more consistent when the perfusion index was 6 or over. In this group, independently from the perfusion index value, the consistency was higher in younger patients compared with aged patients.",
            "output": [
                "Does low perfusion index affect the difference in glucose level between capillary and venous blood?"
            ]
        },
        {
            "id": "task847-100f80b130be4b43948af07676ef2180",
            "input": "Hordeum vulgare L. (HV or barley) is used by traditional healers to treat various inflammatory and cardiovascular diseases, without the knowledge of pharmacologic rationale behind its actions. This study was designed to explore the potential scientific mechanism(s) that could explain the use of Hordeum vulgare in traditional medicine as a treatment for various inflammatory and cardiovascular diseases.', 'A crude extract and its three fractions were prepared from HV and screened for the inhibition of platelet aggregation and various metabolites of cyclooxygenase (COX), lipoxygenase (LOX) pathways of arachidonic acid (AA) metabolism as well as for its effects on certain antioxidant enzymes. Platelet aggregation was monitored using turbidometric principle, AA metabolism through radioimmunoassay and antioxidant enzymes by commercial kits using spectrophotometer.', 'Results show that HV exhibited activities against all human platelet agonists used except adenine diphosphate, and inhibited both COX and LOX pathways of AA metabolism. It also elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). However, these activities were distributed in various fractions of HV. Aqueous fraction was most potent in elevating SOD activity; chloroform fraction had concentrated compounds responsible for COX inhibition while n-hexane seems to possess compounds responsible for LOX inhibition as well as the only fraction enhancing the activity of GPx.",
            "output": [
                "Are multiple pathways responsible for anti-inflammatory and cardiovascular activities of Hordeum vulgare L?"
            ]
        },
        {
            "id": "task847-954e4b223aea42b09ac0789059a7930a",
            "input": "To investigate the eff ect of intestinal trefoil factor (ITF) on the transcriptional activity of ITF promoter and to explore the regulatory mechanism of Janus kinase/signal transducers and activators of transcription (JAK/STAT) on ITF promoter.', \"The 5' flanking sequence of the ITF gene was cloned from human whole blood genomic DNA by PCR. ITF promoter fragment was cloned and inserted into the pGL3-Basic vector to construct recombinant vector. ITF promoter vector was stimulated with ITF at various concentrations and the luciferase activity was measured. The JAK-STAT3 signal transduction pathway was then blocked by a specific inhibitor AG490 to determine the signal pathway involved in ITF promoter activity.\", 'Restriction endonuclease analysis and DNA sequencing confirmed that the recombinant plasmid, containing ITF promoter, was constructed successfully. After transient transfection, the activity of ITF promoter was increased significantly in the presence of ITF (P<0.05). Blockage of the JAK-STAT3 signal transduction pathway with AG490 significantly reduced the ITF promoter activity (P<0.05).",
            "output": [
                "Does [ ITF increase the transcriptional activity of ITF promoter via the JAK-STAT3 signal transduction pathway ]?"
            ]
        },
        {
            "id": "task847-b237bbadeb1a4f2cb02b80a0d4b78a0a",
            "input": "To evaluate pazopanib eye drops in subjects with active subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).', 'Multicountry, randomized, parallel-group, double-masked, active and placebo-controlled, dose-ranging study of eye drops.', 'A total of 510 subjects (93% white; 58% female; mean age, 75.3 years) whose AMD was previously managed by anti-vascular endothelial growth factor intravitreal injections.', 'Treatments administered for 52 weeks included placebo eye drops instilled 4 times daily (n=73); pazopanib 5 mg/ml instilled 3 (n=72) or 4 times daily (n=74); pazopanib 10 mg/ml instilled 2 (n=73), 3 (n=73), or 4 times daily (n=72); or ranibizumab injection administered once every 4 weeks (n=73). In addition, for all eye drop treatment groups, open-label ranibizumab was administered as needed.', 'The main outcome measures were best-corrected visual acuity (BCVA) and injection frequency assessed at week 52. Safety was assessed every 4 weeks and pazopanib plasma concentrations were determined at weeks 4 and 24.', 'At week 52, pazopanib, with allowance for as-needed ranibizumab injections, was noninferior to monthly ranibizumab as well as to as-needed ranibizumab administered with placebo eye drops in maintaining BCVA (estimated BCVA gains of 0.3-1.8 vs. 1.4 vs. 0.2 letters, respectively). Pazopanib treatment did not reduce as-needed ranibizumab injections by \u226550% (prespecified efficacy criterion). At week 52, there were no clinically meaningful changes from baseline in retinal thickness or morphology, CNV size, or lesion characteristics on optical coherence tomography or fluorescein angiography. Complement factor H genotype had no effect on the responses to pazopanib and/or ranibizumab (BCVA, injection rate, or optical coherence tomography/fluorescein angiography changes). Steady-state concentrations of pazopanib in plasma seemed to be reached by week 4. The most common ocular adverse events related to pazopanib and ranibizumab were application site pain (3%) and injection site hemorrhage (1%), respectively. No treatment-related serious adverse events were reported.",
            "output": [
                "Does clinical evaluation of pazopanib eye drop versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration?"
            ]
        },
        {
            "id": "task847-6deddb57334e43ff878e5079ae9d2768",
            "input": "Recent epidemiological evidence suggests that modifying lifestyle by increasing physical activity could be a non-pharmacological approach to improving symptoms and slowing disease progression in Alzheimer's disease and other tauopathies. Previous studies have shown that exercise reduces tau hyperphosphorylation, however, it is not known whether exercise reduces the accumulation of soluble or insoluble tau aggregates and neurofibrillary tangles, which are both neuropathological hallmarks of neurodegenerative tauopathy. In this study, 7-month old P301S tau transgenic mice were subjected to 12-weeks of forced treadmill exercise and evaluated for effects on motor function and tau pathology at 10\\xa0months of age.\", 'Exercise improved general locomotor and exploratory activity and resulted in significant reductions in full-length and hyperphosphorylated tau in the spinal cord and hippocampus as well as a reduction in sarkosyl-insoluble AT8-tau in the spinal cord. Exercise did not attenuate significant neuron loss in the hippocampus or cortex. Key proteins involved in autophagy-microtubule-associated protein 1A/1B light chain 3 and p62/sequestosome 1 -were also measured to assess whether autophagy is implicated in the exercised-induced reduction of aggregated tau protein. There were no significant effects of forced treadmill exercise on autophagy protein levels in P301S mice.",
            "output": [
                "Does long-term treadmill exercise attenuate tau pathology in P301S tau transgenic mice?"
            ]
        },
        {
            "id": "task847-6ca35abb0105471cb32e4f4f4b02bc4b",
            "input": "To evaluate the effect of an acute L-dopa administration on eye-closed resting state electroencephalographic (EEG) activity of cognitively preserved Parkinsonian patients.', \"We examined 24 right-handed patients diagnosed as uncomplicated probable Parkinson's disease (PD). Each patient underwent Unified Parkinson's Disease Rating Scale (UPDRS)-part-III evaluation before and 60 min after an oral load of L-dopa-methyl-ester/carbidopa 250/25 mg. Resting condition eyes-closed EEG data were recorded both pre- and post L-dopa load. Absolute EEG power values were calculated at each scalp derivation for Delta, Theta, Alpha and Beta frequency bands. UPDRS scores (both global and subscale scores) and EEG data (power values of different frequency bands for each scalp derivation) were submitted to a statistical analysis to compare Pre and Post L-Dopa conditions. Finally, a correlation analysis was carried out between EEG spectral content and UPDRS scores.\", 'Considering EEG power spectral analysis, no statistically significant differences arose on Delta and Theta bands after L-dopa intake. Conversely, Alpha and Beta rhythms significantly increased on centro-parietal scalp derivations, as a function of L-dopa administration. Correlation analysis indicated a significant negative correlation between Beta power increase on centro-parietal areas and UPDRS subscores (Rigidity of arms and Bradykinesia). A minor significant negative correlation was also found between Alpha band increase and resting tremor.",
            "output": [
                "Does alpha and beta EEG power reflect L-dopa acute administration in parkinsonian patients?"
            ]
        },
        {
            "id": "task847-d93d481ff91c4966b2baad9aba14324d",
            "input": "Limited data exist on the risk of developing cardiac sarcoidosis (CS) and/or adverse events in sarcoidosis patients. Using LV global longitudinal strain (GLS), an emerging sensitive parameter of LV function, we evaluated the prevalence of subclinical cardiac dysfunction in sarcoidosis and investigated whether LVGLS predicts adverse outcomes in this population.', 'A total of 130 patients with proven sarcoidosis undergoing echocardiography at our referral centre were identified. Following exclusion of those with evidence of CS (n\\u2009=\\u200914) or other pre-existing structural heart disease (n\\u2009=\\u200916), 100 patients (55\\u2009\u00b1\\u200913\\u2009years, 48% male, 90% pulmonary involvement) and 100 age- and gender-matched controls were included. LVGLS was measured by speckle-tracking analysis. The primary endpoint was a composite of all-cause mortality, heart failure hospitalization, device implantation, new arrhythmias, or future development of CS on advanced cardiac imaging modalities. LVGLS was significantly impaired in sarcoidosis patients compared with controls (-17.3\\u2009\u00b1\\u20092.5 vs. -20.0\\u2009\u00b1\\u20091.6%, P\\u2009<\\u20090.001). Overall, 27 patients (27%) reached the endpoint during a median follow-up of 35 months. On Cox proportional hazards model analysis, abnormal 24-h Holter, larger LV end-diastolic diameters, and more impaired LVGLS were significantly associated with the endpoint; however, only LVGLS remained independently associated on multivariate analysis [hazard ratio (HR) 1.4, 95% confidence interval (CI) 1.1-1.7, P\\u2009=\\u20090.006]. Patients with LVGLS less than -17.3% were significantly more likely to be free of the primary endpoint (log-rank P\\u2009=\\u20090.01).",
            "output": [
                "Does subclinical left ventricular dysfunction by echocardiographic speckle-tracking strain analysis relate to outcome in sarcoidosis?"
            ]
        },
        {
            "id": "task847-91400f68d4ce49efb7ba1c7338161b97",
            "input": "Transposable elements form a significant proportion of eukaryotic genomes. Recently, Lexa et al. (Nucleic Acids Res 42:968-978, 2014) reported that plant long terminal repeat (LTR) retrotransposons often contain potential quadruplex sequences (PQSs) in their LTRs and experimentally confirmed their ability to adopt four-stranded DNA conformations.', \"Here, we searched for PQSs in human retrotransposons and found that PQSs are specifically localized in the 3'-UTR of LINE-1 elements, in LTRs of HERV elements and are strongly accumulated in specific regions of SVA elements. Circular dichroism spectroscopy confirmed that most PQSs had adopted monomolecular or bimolecular guanine quadruplex structures. Evolutionarily young SVA elements contained more PQSs than older elements and their propensity to form quadruplex DNA was higher. Full-length L1 elements contained more PQSs than truncated elements; the highest proportion of PQSs was found inside transpositionally active L1 elements (PA2 and HS families).",
            "output": [
                "Are guanine quadruplexes formed by specific regions of human transposable elements?"
            ]
        },
        {
            "id": "task847-76132b34ad7d4eeb88ca677dd16c64ac",
            "input": "Restenosis after vascular intervention remains a major clinical problem. Circulating LR11 has been shown a novel marker of intimal smooth muscle cell (SMC) proliferation in human and animal studies. The present study was performed to clarify the clinical significance of circulating LR11 in patients with stable angina pectoris after coronary stenting.', 'We firstly investigated the circulating sLR11 levels for 28 days after arterial injury in mice, and then assessed time-dependent change in circulating sLR11 level after coronary stenting in a clinical study. Mouse sLR11 levels rapidly increased to 4.0-fold of the control value without cuff placement at postoperative day (POD) 14, and the levels gradually declined to 3.1-fold of the control value until POD 28 in mice. The circulating soluble LR11 levels were measured (before and at 14, 60 and 240 days after coronary stenting in a clinical study of 102 consecutive patients with stable angina pectoris who were treated with percutaneous coronary intervention. Circulating sLR11 levels were significantly increased on days 14 and 60 after the procedure and positively associated with the angiographic late loss index.",
            "output": [
                "Is circulating soluble LR11 , a novel marker of smooth muscle cell proliferation , enhanced after coronary stenting in response to vascular injury?"
            ]
        },
        {
            "id": "task847-c51af1a2e1774b5aafa57f82136976fa",
            "input": "The development of human leukocyte antigen (HLA) antibody responses has been associated with worse clinical outcomes, such as bronchiolitis obliterans syndrome (BOS) and death, in lung transplant recipients (LTRs). However, the role of donor-specific HLA antibody (DSA) responses as a risk factor for poor outcomes remains controversial.', 'We prospectively screened 445 LTRs for DSA at our institution at the time of surveillance bronchoscopies for the first 2 years after transplantation between 2003 and 2008, and evaluated clinical outcomes. For this purpose, we used the combination of panel-reactive antibodies (PRA) by enzyme-linked immunosorbent assay (ELISA) and the Luminex single-antigen bead (SAB) assay (One Lambda, Canoga Park, CA).', 'We detected de novo DSA (dnDSA) in 58 of 445 (13%) LTRs in our cohort. Freedom from BOS was significantly reduced in LTRs with dnDSA versus those without dnDSA (p < 0.001). Using a Cox proportional hazards model, the development of dnDSA was associated with a significantly increased hazard ratio (HR = 6.59 [4.53 to 9.59]; p < 0.001) for BOS and high-grade BOS (Stage \u2265 2) (HR = 5.76 [3.48 to 9.52]; p < 0.001). Freedom from death was significantly reduced in LTRs with dnDSA (p < 0.001), including mortality attributable to BOS (HR = 9.86 [4.91 to 19.78]; p < 0.001).",
            "output": [
                "Are de novo donor-specific HLA antibodies associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation?"
            ]
        },
        {
            "id": "task847-e8023b567ba644a4a600245cb7bd7aee",
            "input": "To conduct a systematic review of studies reporting on the development or validation of comorbidity indices using administrative health data and compare their ability to predict outcomes related to comorbidity (ie, construct validity).', 'We conducted a comprehensive literature search of MEDLINE and EMBASE, until September 2012. After title and abstract screen, relevant articles were selected for review by two independent investigators. Predictive validity and model fit were measured using c-statistic for dichotomous outcomes and R(2) for continuous outcomes.', 'Our review includes 76 articles. Two categories of comorbidity indices were identified: those identifying comorbidities based on diagnoses, using International Classification of Disease codes from hospitalization or outpatient data, and based on medications, using pharmacy data. The ability of indices studied to predict morbidity-related outcomes ranged from poor (C statistic \u2264 0.69) to excellent (C statistic >0.80) depending on the specific index, outcome measured, and study population. Diagnosis-based measures, particularly the Elixhauser Index and the Romano adaptation of the Charlson Index, resulted in higher ability to predict mortality outcomes. Medication-based indices, such as the Chronic Disease Score, demonstrated better performance for predicting health care utilization.",
            "output": [
                "Does a systematic review identify valid comorbidity indices derived from administrative health data?"
            ]
        },
        {
            "id": "task847-1093b4234c96407ea2a2ee2d28c6f131",
            "input": "The consumption of an agrarian diet is associated with a reduced risk for many diseases associated with a 'Westernised' lifestyle. Studies suggest that diet affects the gut microbiota, which subsequently influences the metabolome, thereby connecting diet, microbiota and health. However, the degree to which diet influences the composition of the gut microbiota is controversial. Murine models and studies comparing the gut microbiota in humans residing in agrarian versus Western societies suggest that the influence is large. To separate global environmental influences from dietary influences, we characterised the gut microbiota and the host metabolome of individuals consuming an agrarian diet in Western society.\", 'Using 16S rRNA-tagged sequencing as well as plasma and urinary metabolomic platforms, we compared measures of dietary intake, gut microbiota composition and the plasma metabolome between healthy human vegans and omnivores, sampled in an urban USA environment. Plasma metabolome of vegans differed markedly from omnivores but the gut microbiota was surprisingly similar. Unlike prior studies of individuals living in agrarian societies, higher consumption of fermentable substrate in vegans was not associated with higher levels of faecal short chain fatty acids, a finding confirmed in a 10-day controlled feeding experiment. Similarly, the proportion of vegans capable of producing equol, a soy-based gut microbiota metabolite, was less than that was reported in Asian societies despite the high consumption of soy-based products.",
            "output": [
                "Do comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production?"
            ]
        },
        {
            "id": "task847-4cf5611eed274e4eb8395f172fe9074a",
            "input": "Sox6 is a transcription factor that is crucial for the differentiation and development of cortical interneurons and dopaminergic neurons of the substantia nigra pars compact. Loss-of-function mutations might thus result in complex paroxysmal diseases such as epilepsy syndromes or movement disorders.', 'We present a 15-year-old boy with delayed speech development and attention deficit hyperactivity disorder who presented with a rapid-onset generalized dopa-responsive dystonia.', 'Neurological examination revealed generalized dystonic and frequent athetoid movements of the arms, trunk, and neck. Gait was severely impaired secondary to frequent dystonic postures. Both a resting tremor and action tremors were observed in both hands. Speech was dysarthric but language comprehension was unimpaired. Testing for saccadic dysfunction revealed hypometric horizontal and vertical saccades. Physical examination was otherwise significant for a pectus carinatum and splenomegaly. Laboratory studies, brain magnetic resonance imaging, and electroencephalography were unremarkable. Treatment with levodopa/carbidopa led to a complete and sustained remission of neurological symptoms. Genetic testing revealed a mono-allelic de novo 84-kb deletion on chromosome 11p15.2 encompassing exons 14-16 of the SOX6 gene (chr11: 15944880-16029095, NCBI 37/hg19).",
            "output": [
                "Is disruption of SOX6 associated with a rapid-onset dopa-responsive movement disorder , delayed development , and dysmorphic features?"
            ]
        },
        {
            "id": "task847-83fa085bd638497fb6442e3356b46665",
            "input": "The purpose of this study was to evaluate the role of capsular closure after hip arthroscopy in reduction of the incidence of heterotopic ossification (HO).', 'One hundred (50 study group, 50 control group) consecutive hip arthroscopy procedures with radiographic follow-up of more than 9 weeks were included in the study. The study group consisted of 50 patients in whom capsular closure with 2 No. 1 polydioxanone (PDS) sutures was performed, and a control group consisted of 50 patients in whom the capsule remained open after capsulotomy. HO was assessed by radiographs using the Brooker classification. Statistical analysis of the data was carried out with the \u03c7-square or Fisher exact test and Student t test, when appropriate, at a significance level of .05.', 'Thirty-six (36%) patients had radiographic evidence of postoperative HO (14 patients in the capsular closure group). No significant difference was found regarding sex, side of operation, age, or HO rate between the study and the control groups (P = .778, P = .123, P = .744, and P = .144, respectively). Furthermore, no significant difference was found in the rate of HO with potential clinical significance (Brooker classification > I) between the control and study groups (P = .764).",
            "output": [
                "Does capsular closure affect development of heterotopic ossification after hip arthroscopy?"
            ]
        },
        {
            "id": "task847-7c4bb23195534ec2b6297b565d592a09",
            "input": "The purpose of this study was to examine the osteotomy gap filling rate with new bone after open wedge high tibial osteotomy (HTO) without bone graft and the effects of smoking, lateral hinge fracture, and early full weight bearing.', 'A prospective series (N\\xa0= 70) of open wedge HTOs with the TomoFix plate (DePuy Synthes, Umkirch, Germany) was performed. Radiologic follow-up examinations took place postoperatively, after 6 and 12 weeks, and after 6, 12, and 18 months to measure osteotomy gap filling at each follow-up. Bone healing was compared in smokers versus nonsmokers who underwent open wedge HTOs with intact lateral hinges. Fractured lateral hinges were classified according to the Takeuchi classification and separately analyzed regarding bone healing. Patients were randomly assigned to undergo early (11 days) or standard (6 weeks) full-weight-bearing rehabilitation.', 'A delay in the osteotomy gap filling rate between smokers and nonsmokers could be observed at all follow-up periods, but differences were not significant. A fracture of the lateral hinge was found in 39% of the patients. A type I fracture was observed in 14% of patients, a type II fracture was observed in 13%, and a type III fracture was found in 6%. The highest increase in the osteotomy gap filling rate was observed between 12 weeks and 6 months after surgery in patients with intact lateral hinges. For patients with unstable type II fractures, the highest increase in the gap filling rate was delayed until 6 to 12 months. Early full weight bearing had no effect on the gap filling rate in any of the patient groups evaluated.",
            "output": [
                "Do smoking and unstable hinge fractures cause delayed gap filling irrespective of early weight bearing after open wedge osteotomy?"
            ]
        },
        {
            "id": "task847-7ed5e958768147d9b00eca27a8225916",
            "input": "Deep erythema and inflammation after re-epithelialization of superficial wounds is a sign of scar formation. Corticosteroids may prevent scarring by suppression of inflammation and fibroblast activity. Tretinoin may increase the efficacy of corticosteroids in this setting.', 'To evaluate the efficacy of corticosteroids plus tretinoin for prevention of scars after superficial wounds.', 'In a retrospective study of patients with superficial partial thickness thermal skin burn, we compared the patients who received clobetasol plus tretinoin after re-epithelialization with patients who did not receive any medication. Clobetasol propionate 0.05% ointment was used twice daily with overnight occlusive dressing in conjunction with twice weekly topical tretinoin 0.05% cream.', 'Among 43 patients who had light pink or no erythema after re-epithelialization and consequently did not receive clobetasol\\u2009+\\u2009tretinoin, no scar was developed. Among patients who had deep erythema after re-epithelialization, rate of scar formation was significantly higher in 14 patients who did not receive clobetasol\\u2009+\\u2009tretinoin than in 21 patients who received clobetasol\\u2009+\\u2009tretinoin (64% and 19%, respectively; p\\u2009=\\u20090.01).",
            "output": [
                "Is topical clobetasol in conjunction with topical tretinoin effective in preventing scar formation after superficial partial-thickness burn ulcers of the skin : A retrospective study?"
            ]
        },
        {
            "id": "task847-d25c7dc5c9504ff9988fd53e7cec7a37",
            "input": "Osteoarthritis (OA) is associated with a gradual reduction in the interstitial osmotic pressure within articular cartilage. The aim of this study was to compare the effects of sudden and gradual hypo-osmotic challenge on chondrocyte morphology and biomechanics.', 'Bovine articular chondrocytes were exposed to a reduction in extracellular osmolality from 327 to 153 mOsmol/kg applied either suddenly (<5 s) or gradually (over 180 min). Temporal changes in cell diameter and the existence of regulatory volume decrease (RVD) were quantified along with changes in cortical actin and chromatin condensation. The cellular viscoelastic mechanical properties were determined by micropipette aspiration.', 'In response to a sudden hypo-osmotic stress, 66% of chondrocytes exhibited an increase in diameter followed by RVD, whilst 25% showed no RVD. By contrast, cells exposed to gradual hypo-osmotic stress exhibited reduced cell swelling without subsequent RVD. There was an increase in the equilibrium modulus for cells exposed to sudden hypo-osmotic stress. However, gradual hypo-osmotic challenge had no effect on cell mechanical properties. This cell stiffening response to sudden hypo-osmotic challenge was abolished when actin organization was disrupted with cytochalasin D or RVD inhibited with REV5901. Both sudden and gradual hypo-osmotic challenge reduced cortical F-actin distribution and caused chromatin decondensation.",
            "output": [
                "Does the rate of hypo-osmotic challenge influence regulatory volume decrease ( RVD ) and mechanical properties of articular chondrocytes?"
            ]
        },
        {
            "id": "task847-8188c78a4b784e8697923a060011f0bb",
            "input": "Augmenter of liver regeneration (ALR, encoded by GFER) is a widely distributed pleiotropic protein originally identified as a hepatic growth factor. However, little is known about its roles in hepatic physiology and pathology. We created mice with liver-specific deletion of ALR to study its function.', 'We developed mice with liver-specific deletion of ALR (ALR-L-KO) using the albumin-Cre/LoxP system. Liver tissues were collected from ALR-L-KO mice and ALR(floxed/floxed) mice (controls) and analyzed by histology, reverse-transcription polymerase chain reaction, immunohistochemistry, electron microscopy, and techniques to measure fibrosis and lipids. Liver tissues from patients with and without advanced liver disease were determined by immunoblot analysis.', 'Two weeks after birth, livers of ALR-L-KO mice contained low levels of ALR and adenosine triphosphate (ATP); they had reduced mitochondrial respiratory function and increased oxidative stress, compared with livers from control mice, and had excessive steatosis, and hepatocyte apoptosis. Levels of carbamyl-palmitoyl transferase 1a and ATP synthase subunit ATP5G1 were reduced in livers of ALR-L-KO mice, indicating defects in mitochondrial fatty acid transport and ATP synthesis. Electron microscopy showed mitochondrial swelling with abnormalities in shapes and numbers of cristae. From weeks 2-4 after birth, levels of steatosis and apoptosis decreased in ALR-L-KO mice, and numbers of ALR-expressing cells increased, along with ATP levels. However, at weeks 4-8 after birth, livers became inflamed, with hepatocellular necrosis, ductular proliferation, and fibrosis; hepatocellular carcinoma developed by 1 year after birth in nearly 60% of the mice. Hepatic levels of ALR were also low in ob/ob mice and alcohol-fed mice with liver steatosis, compared with controls. Levels of ALR were lower in liver tissues from patients with advanced alcoholic liver disease and nonalcoholic steatohepatitis than in control liver tissues.",
            "output": [
                "Does liver-specific deletion of augmenter of liver regeneration accelerate development of steatohepatitis and hepatocellular carcinoma in mice?"
            ]
        },
        {
            "id": "task847-62ecfcd1d88f477d8de5360eda8ffa5e",
            "input": "Esophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing 2 entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen-driven, TH2-associated allergic disorder, whereas the cause of PPI-REE remains a mystery.', 'In this study, our aim was to investigate the pathogenesis of PPI-REE by using a recently described EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts and to determine whether PPI therapy reverses any esophageal transcriptional abnormalities.', 'We evaluated the EDP signature in biopsy samples obtained from adult and pediatric patients with PPI-REE from 4 institutions and compared the pre- and post-PPI therapy expression profiles of these subjects with those of patients with active EoE.', 'The EDP differentiated patients with EoE from control subjects with 100% accuracy among the 4 clinical sites. Bioinformatics analysis revealed largely overlapping transcriptomes between patients with PPI-REE and those with EoE, including the genes for eosinophil chemotaxis (eotaxin 3, CCL26), barrier molecules (desmoglein 1, DSG1), tissue remodeling (periostin, POSTN), and mast cells (carboxypeptidase A, CPA3). PPI monotherapy alone almost completely reversed the allergic inflammatory transcriptome of patients with PPI-REE. Furthermore, we identified a set of candidate genes to differentiate patients with EoE from those with PPI-REE before treatment.",
            "output": [
                "Does transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveal proton pump inhibitor-reversible allergic inflammation?"
            ]
        },
        {
            "id": "task847-bbedb38e39b749e8aa6c63715d242800",
            "input": "We compared the results of laboratory examinations, echocardiography, arterial stiffness, central blood pressure (BP) and ambulatory BP monitoring (ABPM) between treatment-na\u00efve patients with low normal thyroid-stimulating hormone (TSH) and those with high normal TSH levels.', 'A total of 285 consecutively-eligible patients with both treatment-na\u00efve hypertension and euthyroid were divided into two groups: those with low-normal TSH (0.40-1.99 \u03bcIU/mL, group 1) and high-normal TSH (2.00-4.50 \u03bcIU/mL, group 2) and compared according to group and gender.', 'Males were divided into group 1 (n = 113, 68.9%) and group 2 (n = 51, 31.1%) and females were divided into group 1 (n = 71, 58.7%) and group 2 (n = 50, 41.3%). Multivariate analyses revealed that the augmentation index (71.0 [adjusted mean] \u00b1 1.7 [standard error] vs. 78.8 \u00b1 2.5%, P = 0.045), central systolic BP (SBP) (143.3 \u00b1 2.1 vs. 153.0 \u00b1 3.2 mmHg, P = 0.013), systemic vascular resistance (SVR, 21.4 \u00b1 0.6 vs. 23.9 \u00b1 0.9 mmHg/L/min, P = 0.027), SBP during daytime (144.1 \u00b1 1.4 vs. 151.6 \u00b1 2.1 mmHg, P=0.004) and nighttime (130.4 \u00b1 1.6 vs. 138.5 \u00b1 2.5 mmHg, P=0.008), and nighttime pulse pressure (PP, 47.2 \u00b1 0.9 vs. 51.7 \u00b1 1.4 mmHg, P = 0.010) were significantly higher while cardiac output (5.4 \u00b1 0.1 vs. 4.8 \u00b1 0.2L/min, P = 0.043) and PP amplification (1.02 \u00b1 0.02 vs. 0.94 \u00b1 0.03, P = 0.039) were significantly lower in the male group 2 than in the male group 1. However, there were no significant differences between the two groups in females.",
            "output": [
                "Is a high normal thyroid-stimulating hormone associated with arterial stiffness , central systolic blood pressure , and 24-hour systolic blood pressure in males with treatment-na\u00efve hypertension and euthyroid?"
            ]
        },
        {
            "id": "task847-2b1be5d71d4c482695d0766dcfc97721",
            "input": "Rotenone is an environmental neurotoxin that induces accumulation of \u03b1-synuclein and degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc), but the molecular mechanisms are not fully understood. We investigated whether rotenone induced impairment of autophagic flux and lysosomal functions.', \"Autophagy flux, accumulation of \u03b1-synuclein, lysosomal membrane integrity and neurodegeneration were assessed in the rotenone-treated rat model and PC12 cells, and the effects of the autophagy inducer trehalose on rotenone's cytotoxicity were also studied.\", 'Rotenone administration significantly reduced motor activity and caused a loss of tyrosine hydroxylase in SNpc of Lewis rats. The degeneration of nigral dopaminergic neurons was accompanied by the deposition of \u03b1-synuclein aggregates, autophagosomes and redistribution of cathepsin D from lysosomes to the cytosol. In cultured PC12 cells, rotenone also induced increases in protein levels of \u03b1-synuclein, microtubule-associated protein 1 light chain 3-II, Beclin 1, and p62. Rotenone increased lysosomal membrane permeability as evidenced by leakage of N-acetyl-beta-d-glucosaminidase and cathepsin D, the effects were blocked by reactive oxygen species scavenger tiron. Autophagy inducer trehalose enhanced the nuclear translocation of transcription factor EB, accelerated the clearance of autophagosomes and \u03b1-synuclein and attenuated rotenone-induced cell death of PC12 cells. Meanwhile, administration of trehalose to rats in drinking water (2%) decreased rotenone-induced dopaminergic neurons loss in SNpc.",
            "output": [
                "Does rotenone impair autophagic flux and lysosomal functions in Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-0ac81813dc5d4f4185699f77139dac48",
            "input": "Acute pancreatitis (AP) is a systemic inflammatory disease, and cytokines are suggested to be related to the course of AP. Obesity and central fat distribution are considered to have been associated with severe AP. This study investigated the profile of inflammatory cytokines in AP to determine how they are related to obesity, central fat distribution, and AP severity.', 'Fifty-nine patients with AP were prospectively enrolled in the study. Body mass index and waist circumference were obtained at admission. Serum levels of inflammatory cytokines, IL-I\u03b2, IL-1ra, IL-6, TNF-\u03b1, sTNFR-I, and sTNFR-II, were measured on day 1 and 2 of AP.', 'Of the patients included in the study, 19 (32%) were overweight, 23 (39%) had central fat distribution, and 23 (39%) had moderate AP. IL-1ra and IL-6 were significantly higher in overweight patients compared with non-overweight patients. IL-1ra, IL-6, TNF-\u03b1, and sTNFR-I were significantly higher in patients with central fat distribution compared with patients with non-central fat distribution. IL-6, sTNFR-I, and sTNFR-II were significantly higher in patients with moderate pancreatitis compared to those with mild pancreatitis. Among the six cytokines, IL-6 was commonly elevated in patients with central fat distribution, overweight, and moderate AP. The areas under the receiver operating characteristic curves of IL-6 for predicting the association with overweight, central fat distribution, and AP severity were 0.678, 0.716, and 0.801, respectively (P < 0.05).",
            "output": [
                "Is interleukin-6 associated with obesity , central fat distribution , and disease severity in patients with acute pancreatitis?"
            ]
        },
        {
            "id": "task847-49726a4e87ca4143bed21a5e1c2b10b2",
            "input": "Troponins may be elevated in patients with pneumonia, but associations with myocardial infarction (MI) and with platelet activation are still undefined.', 'The aim of this study was to investigate the relationship between troponin elevation and in\\xa0vivo markers of platelet activation in the early phase of hospitalization of patients affected by community-acquired pneumonia.', 'A total of 278 consecutive patients hospitalized for community-acquired pneumonia, who were followed up until discharge, were included. At admission, platelet activation markers such as plasma soluble P-selectin, soluble CD40\\xa0ligand, and serum thromboxane B2 (TxB2) were measured. Serum high-sensitivity cardiac troponin T levels and electrocardiograms were obtained every 12 and 24 h, respectively.', 'Among 144 patients with elevated high-sensitivity cardiac troponin T, 31 had signs of MI and 113 did not. Baseline plasma levels of soluble P-selectin and soluble CD40 ligand and serum TxB2 were significantly higher in patients who developed signs of MI. Logistic regression analysis showed plasma soluble CD40 ligand (p\\xa0< 0.001) and soluble P-selectin (p\\xa0< 0.001), serum TxB2 (p\\xa0= 0.030), mean platelet volume (p\\xa0= 0.037), Pneumonia Severity Index score (p\\xa0=\\xa00.030), and ejection fraction (p\\xa0= 0.001) to be independent predictors of MI. There were no significant differences in MI rate between the 123 patients (45%) taking aspirin (100 mg/day) and those who were not aspirin treated (12%\\xa0vs.\\xa010%; p\\xa0= 0.649). Aspirin-treated patients with MIs had higher serum TxB2 compared with those without MIs\\xa0(p\\xa0= 0.005).",
            "output": [
                "Is platelet activation associated with myocardial infarction in patients with pneumonia?"
            ]
        },
        {
            "id": "task847-5e4d046156c64fd087c58dbeab5b9b23",
            "input": "Dipeptidyl peptidase-4 (DPP4) was recently proposed as a novel adipokine linked to insulin resistance (IR). As IR represents a cluster of disorders in hepatic and muscle cell insulin signalisation, we aimed to assess the possible correlation between fasting serum DPP4 activity, IR and liver enzymes in order to elucidate the question of hepatic contribution to serum DPP4 activity.', 'This cross-sectional study comprised 44 T1DM patients aged 18 to 65years. IR was estimated using the equation derived from euglycemic-hyperinsulinemic clamp studies-estimated glucose disposal rate (eGDR). DPP4 serum activity was determined spectrophotometrically as a rate of cleavage of 7-amino-4-methyl coumarin (AMC) from H-Gly-Pro-AMC. The patients were divided into two groups according to the mean value of fasting serum DPP4 activity (31.42U/L).', 'The group with lower fasting serum DPP4 activity had lower mean rate of liver biomarkers alanine aminotransferase (ALT) (p=0.001) and aspartate aminotransferase (AST) (p=0.002) while higher eGDR (p=0.003) compared to group with higher DPP4 activity. DPP4 activity showed positive correlation with AST (r=0.358, p=0.017) and ALT (r=0.364, p=0.015) while negative correlation with eGDR (r=-0.612, p<0.001). ALT remained positively associated with fasting serum DPP4 activity after controlling for age, gender, diabetes duration, the use of statins and antihypertensives (p=0.025).",
            "output": [
                "Is fasting serum dipeptidyl peptidase-4 activity independently associated with alanine aminotransferase in type 1 diabetic patients?"
            ]
        },
        {
            "id": "task847-d174f4ce0d9b4f05b1e787b49cd74134",
            "input": "To test our hypothesis that initiating therapy with a combination of agents known to improve insulin secretion and insulin sensitivity in subjects with new-onset diabetes would produce greater, more durable reduction in glycated haemoglobin (HbA1c) levels, while avoiding hypoglycaemia and weight gain, compared with sequential addition of agents that lower plasma glucose but do not correct established pathophysiological abnormalities.', 'Drug-na\u00efve, recently diagnosed subjects with type 2 diabetes mellitus (T2DM) were randomized in an open-fashion design in a single-centre study to metformin/pioglitazone/exenatide (triple therapy; n\\u2009=\\u2009106) or an escalating dose of metformin followed by sequential addition of sulfonylurea and glargine insulin (conventional therapy; n\\u2009=\\u2009115) to maintain HbA1c levels at <6.5% for 2\\u2009years.', 'Participants receiving triple therapy experienced a significantly greater reduction in HbA1c level than those receiving conventional therapy (5.95 vs. 6.50%; p\\u2009<\\u20090.001). Despite lower HbA1c values, participants receiving triple therapy experienced a 7.5-fold lower rate of hypoglycaemia compared with participants receiving conventional therapy. Participants receiving triple therapy experienced a mean weight loss of 1.2\\u2009kg versus a mean weight gain of 4.1\\u2009kg (p\\u2009<\\u20090.01) in those receiving conventional therapy.",
            "output": [
                "Is initial combination therapy with metformin , pioglitazone and exenatide more effective than sequential add-on therapy in subjects with new-onset diabetes . Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes ( EDICT ) : a randomized trial?"
            ]
        },
        {
            "id": "task847-4a0a0b018e37481796c9f575720b55f2",
            "input": "Obesity and hemorrhagic shock following trauma are predictors of mortality but have conflicting effects on coagulation. Following hemorrhage, tissue injury and hypoperfusion lead to acute traumatic coagulopathy (ATC), producing a hypocoagulable state. Inversely, obesity promotes clotting and impairs fibrinolysis to yield a hypercoagulable state. High rates of venous thromboembolism, organ failure, and early mortality may be caused by hypercoagulability in obese patients. We hypothesize that obesity prevents the development of ATC following injury-induced hemorrhagic shock.', 'Male Sprague-Dawley rats (250-275 g) were fed a high-fat diet (32%kcal from fat) for 4 weeks to 6 weeks and diverged into obesity-resistant (OR, n = 9) and obesity-prone (OP, n = 9) groups. Age-matched control (CON) rats were fed normal diet (10% kcal from fat, n = 9). Anesthetized rats were subjected to an uncontrolled hemorrhage by a Grade V splenic injury to a mean arterial pressure (MAP) of 40 mm Hg. Hypotension (MAP, 30-40 mm Hg) was maintained for 30 minutes to induce shock. MAP, heart rate, lactate, base excess, cytokines, blood loss, and thrombelastography (TEG) parameters were measured before and after hemorrhagic shock.', 'At baseline, OP rats exhibited a shorter time to 20-mm clot (K), and higher rate of clot formation (\u03b1 angle), clot strength (maximal amplitude), and coagulation index, compared with the CON rats (p < 0.05), indicating enhanced coagulation. Physiologic parameters following shock were similar between groups. In the CON and OR rats, shock prolonged the time to clot initiation (R) and K and decreased \u03b1 angle and coagulation index (all p < 0.05 vs. baseline). In contrast, shock had no effect on these TEG parameters in the OP rats. Maximal amplitude was the only TEG parameter affected by shock in the OP rats, which was decreased in all groups.",
            "output": [
                "Does diet-induced obesity prevent the development of acute traumatic coagulopathy?"
            ]
        },
        {
            "id": "task847-0d3ba80858ab4148a295b6f5a413e887",
            "input": "Acute rejection (AR) after organ transplantation results in transplant arteriosclerosis (TA). Endothelial progenitor cells (EPCs) are involved in tissue repair and blood vessel formation but are suspected to be a cause of TA.', 'In this study, we introduced a syngeneic and allogeneic abdominal aortic transplant model with C57BL/6 and BALB/c mice. Syngeneic and allogeneic grafts were histopathologically analyzed after transplantation. Bone marrow-derived EPCs were injected into transplant model animals to observe their distribution and temporal concentration changes. Changes of vascular endothelial growth factor receptor 1 (VEGFR-1), phosphorylated VEGFR-1 (pVEGFR-1), VEGFR-2, pVEGFR-2, protein kinase B (Akt), pAkt, extracellular signal-regulated kinase 1 (Erk1), pErk1 levels in EPCs upon VEGF165 and the VEGFR inhibitor Vandetanib exposure were analyzed in\\xa0vitro with western blotting.', 'In the allogeneic transplant group, two weeks after transplantation, formations of new intima layers could be observed, and its proliferation gradually increased to four and six weeks post-transplantation (p\\xa0<\\xa00.05), accompanied by significant arterial stenoses. Exogenous EPCs mainly localized to the damaged sites of the transplant arteries. In\\xa0vivo, Vandetanib caused a significant dose dependent decrease of transplant hyperplasia (p\\xa0<\\xa00.05) and inhibited VEGF related proliferation, migration and adhesion of EPCs.",
            "output": [
                "Do endothelial progenitor cells induce transplant arteriosclerosis via VEGFR-1/2 activity?"
            ]
        },
        {
            "id": "task847-08dd98578d974934a50b714296d3c27a",
            "input": "To investigate serum beta2-glycoprotein I-low-density lipoprotein (\u03b22-GPI-LDL) and oxidized low-density lipoprotein (ox-LDL) levels in type 2 diabetes mellitus (T2DM) patients, and to further evaluate the associations of \u03b22-GPI-LDL with ox-LDL in vivo and with the presence of diabetic microvascular complications.', 'We determined \u03b22-GPI-LDL, ox-LDL and small dense low density lipoprotein cholesterol (sdLDL-C) levels in 236 T2DM patients with or without microvascular complications and 75 controls. The correlation analyses, multiple linear regression analyses and logistic regression analyses were performed, respectively.', 'Compared with controls, \u03b22-GPI-LDL and ox-LDL levels were significantly elevated in both groups of T2DM patients and those with microvascular complications exhibited the more significant increase than those without complications. Serum \u03b22-GPI-LDL levels were positively correlated with ox-LDL as well as sdLDL-C levels in T2DM patients. Multiple linear regression analyses showed that ox-LDL was one of the independent determinants of \u03b22-GPI-LDL levels. Logistic regression analyses indicated that elevated \u03b22-GPI-LDL and ox-LDL levels had significant predictive values for diabetic microvascular complications.",
            "output": [
                "Are elevated beta2-glycoprotein I-low-density lipoprotein levels associated with the presence of diabetic microvascular complications?"
            ]
        },
        {
            "id": "task847-ebec5433905f41f093fc41ee69a77e38",
            "input": "The blotchy mouse caused by mutations of ATP7A develops low blood copper and aortic aneurysm and rupture. Although the aortic pathologies are believed primarily due to congenital copper deficiencies in connective tissue, perinatal copper supplementation does not produce significant therapeutic effects, hinting additional mechanisms in the symptom development, such as an independent effect of the ATP7A mutations during adulthood.', 'We investigated if bone marrow from blotchy mice contributes to these symptoms. For these experiments, bone marrow from blotchy mice (blotchy marrow group) and healthy littermate controls (control marrow group) was used to reconstitute recipient mice (irradiated male low-density lipoprotein receptor -/- mice), which were then infused with angiotensin II (1,000 ng/kg/min) for 4 weeks.', \"By using Mann-Whitney U test, our results showed that there was no significant difference in the copper concentrations in plasma and hematopoietic cells between these 2 groups. And plasma level of triglycerides was significantly reduced in blotchy marrow group compared with that in control marrow group (P < 0.05), whereas there were no significant differences in cholesterol and phospholipids between these 2 groups. Furthermore, a bead-based multiplex immunoassay showed that macrophage inflammatory protein (MIP)-1\u03b2, monocyte chemotactic protein (MCP)-1, MCP-3, MCP-5, tissue inhibitor of metalloproteinases (TIMP)-1, and vascular endothelial growth factor (VEGF)-A production was significantly reduced in the plasma of blotchy marrow group compared with that in control marrow group (P < 0.05). More important, although angiotensin II infusion increased maximal external aortic diameters in thoracic and abdominal segments, there was no significant difference in the aortic diameters between these 2 groups. Furthermore, aortic ruptures, including transmural breaks of the elastic laminae in the abdominal segment and lethal rupture in the thoracic segment, were observed in blotchy marrow group but not in control marrow group; however, there was no significant difference in the incidence of aortic ruptures between these 2 groups (P = 0.10; Fisher's exact test).",
            "output": [
                "Is bone marrow from blotchy mice dispensable to regulate blood copper and aortic pathologies but required for inflammatory mediator production in LDLR-deficient mice during chronic angiotensin II infusion?"
            ]
        },
        {
            "id": "task847-019e2774e32a464d85af3ff3daa8b75f",
            "input": "Animal and human studies suggest that programing of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the development of obesity, but human studies of biological indicators of HPA axis activity are lacking. We studied the association between levels of the stress hormone cortisol during pregnancy and overweight offspring during childhood into adolescence.', 'Salivary samples from 655 Danish pregnant women with singleton pregnancies (1989-1991) were collected once in the morning and once in the evening in their second and third trimester. We followed the offspring from two to 16 years of age with at least one measurement of height and weight, and classified their body mass index into overweight and normal weight. The adjusted relative difference in median salivary cortisol (with 95% confidence interval (CI)) during pregnancy (the four samples), in second and third trimester (morning and evening samples) between overweight and normal weight offspring was estimated. Furthermore, the adjusted median ratio between morning and evening maternal salivary cortisol level was estimated for normal weight and overweight children. All the analyses were stratified into the equal age groups: 2-6, 7-11, and 12-16 years.', 'We found non-significant higher maternal cortisol levels during pregnancy in offspring that were overweight at the age of 2-6, 7-11 and 12-16 years than in normal weight peers; adjusted relative difference in median salivary cortisol 11% (95% CI: -2; 25), 6% (95% CI: -7; 20), and 9% (95% CI: -4; 24), respectively. A statistically significantly higher level of maternal cortisol was found in the second trimester in 2-6-year-old and 12-16-year-old overweight offspring; relative difference 19% (95% CI: 3; 37), and 20% (95% CI: 3; 41), respectively. The median ratio between morning and evening maternal salivary cortisol level was similar for overweight and normal weight children; e.g. at age 2-6 years in third trimester 4.31 (95% CI: 4.05; 4.60)nmol/l and 4.28 (95% CI: 3.60; 5.09)nmol/l, respectively (P=0.93).",
            "output": [
                "Are maternal salivary cortisol levels during pregnancy positively associated with overweight children?"
            ]
        },
        {
            "id": "task847-9ae2c4d67861496a892ca267439ba875",
            "input": "The optimal clinical context for initiation of salvage androgen deprivation therapy (SADT) following the biochemical recurrence of localized prostate cancer remains controversial. We chose to investigate if disease burden at time of SADT initiation is associated with clinical outcomes following biochemical failure (BF) post-salvage radiation therapy (SRT).', 'Medical records of 575 patients receiving SRT at a single institution from 1986-2010 were retrospectively reviewed. Of 250 patients experiencing BF post-SRT, 172 had a calculable prostate-specific antigen doubling time (PSADT) prior to SADT initiation. These patients comprise the analyzed cohort and were divided into four groups based on characteristics at SADT initiation: those with PSADTs >3 months without distant metastasis (DM) (group 1 [less advanced disease], n=62), those with PSADTs <3 months without DM (group 2 [more advanced disease], n=28), those with DM (group 3 [more advanced disease], n=32), and those not receiving SADT during follow-up (group 4, n=50). Endpoints included prostate cancer-specific mortality (PCSM) and overall mortality (OM). Kaplan-Meier methods were used to estimate survival, and Cox proportional hazards models were used for multivariate analysis.', 'Median follow-up post-SRT was 7.9 years. Patients starting SADT with more advanced disease were at significantly increased risk for PCSM (hazard ratio [HR]:2.8, 95% confidence interval [CI]: 1.4-5.6, p=0.005) and OM (HR:1.9, 95% CI: 1.0-3.5, p=0.04) compared to those receiving SADT with less advanced disease. PCSM and OM did not significantly differ between groups 1 and 4 or groups 2 and 3. Of note, patients in group 4 had very long PSADTs (median = 27.0 months) that were significantly longer than those of group 1 (median = 6.0 months) (p<0.001). Multivariate analysis including groups 1-3 found a pre-SADT PSADT <3 months to be the most significant predictor of PCSM (HR:4.2, 95% CI: 1.6-11.1, p=0.004) and the only significant predictor of OM (HR:2.9, 95% CI: 1.3-6.7, p=0.01).",
            "output": [
                "Is less advanced disease at initiation of salvage androgen deprivation therapy associated with decreased mortality following biochemical failure post-salvage radiation therapy?"
            ]
        },
        {
            "id": "task847-88c7a7d53fd84660965515a8097dee0a",
            "input": "Hepatocellular carcinoma is one of the most common malignancies worldwide. The only curative treatment is surgery. As hepatocellular carcinoma is often associated with liver cirrhosis, patients are at risk for postoperative liver failure. In the recent years, platelets are thought to play an important role in liver regeneration.The aim of this study was to discover the relevance of postoperative platelet counts after liver resection for hepatocellular carcinoma.', 'Data of 68 patients who underwent liver resection for hepatocellular carcinoma between July 2007 and July 2012 in a single centre were analysed. Postoperative morbidity and mortality were evaluated in regard to postoperative platelet counts. Comparative analysis between patients with platelet counts \u2264100 2x109/ l and >100 x109/ l at d1 was performed in regard to postoperative outcome.', 'Within this cohort, 43 patients (63%) suffered from histologically proven liver cirrhosis. Postoperative mortality was statistically significant associated with postoperative reduced platelet counts. Comparative analysis showed significantly elevated postoperative bilirubin levels and lower prothrombin time in patients with platelet counts \u2264 100 1x109/ l at d1.",
            "output": [
                "Is low postoperative platelet count associated with negative outcome after liver resection for hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-772ccc15358041dfa47988ab0bd8c99f",
            "input": "To investigate the association between early menarche (menarche age < 12 years) and Type 2 diabetes mellitus in young and middle-aged Korean women.', 'We analysed data for 4657 women aged 20-50 years from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV) (2007-2009).', 'The prevalence of Type 2 diabetes was 2.8%. Women with early menarche had a higher prevalence of impaired fasting glucose than did women with later menarche (age \u2265 12 years) in the 20-30 age group (7.4% vs. 3.0%), and a higher prevalence of diabetes in the 30-40 (6.3% vs. 1.7%) and 40-50 (18.5% vs. 4.4%) age groups. The odds ratio (OR) of Type 2 diabetes in women with early menarche was 3.61 [95% confidence interval (CI), 1.90-6.88] after adjusting for age. In multivariate regression, the OR of Type 2 diabetes decreased to 2.52 (95% CI, 1.29-4.94) after further adjusting for BMI. However, the OR decreased to 2.04 (95% CI, 0.95-4.39) without significance after adjusting for HOMA-IR.",
            "output": [
                "Does early menarche increase the risk of Type 2 diabetes in young and middle-aged Korean women?"
            ]
        },
        {
            "id": "task847-cc23fcb001c34da5857d24d10f5b3737",
            "input": "Extracorporeal membrane oxygenation (ECMO) support is often required in the management of perioperative congenital heart surgery (CHS) patients. However, 24-hour in-hospital congenital cardiac surgical coverage (24-CCSC) is not available at all institutions. The purpose of this study is to evaluate the effect of 24-CCSC on perioperative ECMO outcomes in CHS patients.', \"An institutional review board approved, retrospective review of 128 perioperative CHS ECMO patients at a single, quaternary care children's hospital between January 2003 and December 2012 was performed. Primary endpoints evaluated were mortality in children supported with ECMO after undergoing cardiac surgery and ECMO-related morbidity after initiation of 24-CCSC with advanced congenital cardiac surgical fellows. Patients were divided into 2 groups based on whether 24-CCSC was absent (cohort 1: January 2003 to July 2007) or present (cohort 2: August 2007 to December 2012) at the time of ECMO management.\", 'The surgical procedures performed were similar in both cohorts based on STAT Mortality Categories (5 Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories). The overall mortality rate in children supported with ECMO after undergoing cardiac surgery was 53%. This mortality was significantly reduced from 68% to 43% (p\\xa0= 0.007) with\\xa024-CCSC. Multivariate logistic regression analysis revealed that 24-CCSC (p\\xa0= 0.009) and lower STAT Mortality Category (p\\xa0= 0.042) were independent predictors of operative survival. Cardiac arrhythmias (36% to 16%; p\\xa0= 0.012) and pulmonary complications (32% to 8%; p < 0.001) were significantly reduced with 24-CCSC.",
            "output": [
                "Does twenty-four hour in-hospital congenital cardiac surgical coverage improve perioperative ECMO support outcomes?"
            ]
        },
        {
            "id": "task847-d89054858dc64973844810a7ec71b484",
            "input": "Although early primary repair of tetralogy of Fallot has gained wider acceptance, there is some speculation that repair at a younger age may be associated with increased morbidity and resource utilization.', 'A retrospective review of all consecutive patients undergoing tetralogy of Fallot repair between September 2004 and December 2011 was performed. Primary end points were hospital charges, and surrogates of postoperative hospital resource utilization, including ventilation time, intensive care unit (ICU) stay, and hospital stay. The secondary end point was operative death. Logistic regression analysis was used to determine factors associated with increased postoperative hospital resource utilization.', 'Among 164 patients in the study, there was 1 hospital death (0.6%). After excluding 9 patients who had palliative procedures before their repair, 155 comprised the primary repair group. Multivariate linear regression analysis revealed prematurity (p\\xa0= 0.018), a nonelective operation (p < 0.001), and major extracardiac anomalies (p\\xa0= 0.003) were independent predictors of increased postoperative hospital charges. Prematurity (p < 0.002), low birth weight (p\\xa0= 0.047), and major extracardiac anomalies (p < 0.001) were significant predictors of increased ventilation time. Prematurity (p < 0.001), a nonelective operation (p < 0.001), and low birth weight (p\\xa0= 0.048) significantly increased ICU length of stay. A nonelective operation (p\\xa0= 0.025) and major extracardiac anomalies (p < 0.001) were predictors of an increased hospital stay. Younger age at repair was not associated with any increase in ventilation time, ICU stay, hospital stay, or with an increase in hospital charges.",
            "output": [
                "Does early primary repair of tetralogy of Fallot lead to increased postoperative resource utilization?"
            ]
        },
        {
            "id": "task847-d80d4dd412fe483dba79f2df3f8bc35e",
            "input": "The Royal College of Physicians (RCPL) National Early Warning Score (NEWS) escalates care to a doctor at NEWS values of \u22655 and when the score for any single vital sign is 3.', \"We calculated the 24-h risk of serious clinical outcomes for vital signs observation sets with NEWS values of 3, 4 and 5, separately determining risks when the score did/did not include a single score of 3. We compared workloads generated by the RCPL's escalation protocol and for aggregate NEWS value alone.\", \"Aggregate NEWS values of 3 or 4 (n=142,282) formed 15.1% of all vital signs sets measured; those containing a single vital sign scoring 3 (n=36,207) constituted 3.8% of all sets. Aggregate NEWS values of either 3 or 4 with a component score of 3 have significantly lower risks (OR: 0.26 and 0.53) than an aggregate value of 5 (OR: 1.0). Escalating care to a doctor when any single component of NEWS scores 3 compared to when aggregate NEWS values \u22655, would have increased doctors' workload by 40% with only a small increase in detected adverse outcomes from 2.99 to 3.08 per day (a 3% improvement in detection).",
            "output": [
                "Are aggregate National Early Warning Score ( NEWS ) values more important than high scores for a single vital signs parameter for discriminating the risk of adverse outcomes?"
            ]
        },
        {
            "id": "task847-cbd36a7ccf404ee58731c7f1478fbd34",
            "input": "Much evidence suggests that plant communities on infertile soils are relatively insensitive to increased water deficit caused by increasing temperature and/or decreasing precipitation. However, a multi-decadal study of community change in the western USA does not support this conclusion. This paper tests explanations related to macroclimatic differences, overstorey effects on microclimate, variation in soil texture and plant functional traits.', 'A re-analysis was undertaken of the changes in the multi-decadal study, which concerned forest understorey communities on infertile (serpentine) and fertile soils in an aridifying climate (southern Oregan) from 1949-1951 to 2007-2008. Macroclimatic variables, overstorey cover and soil texture were used as new covariates. As an alternative measure of climate-related change, the community mean value of specific leaf area was used, a functional trait measuring drought tolerance. We investigated whether these revised analyses supported the prediction of lesser sensitivity to climate change in understorey communities on infertile serpentine soils.', 'Overstorey cover, but not macroclimate or soil texture, was a significant covariate of community change over time. It strongly buffered understorey temperatures, was correlated with less change and averaged >50 % lower on serpentine soils, thereby counteracting the lower climate sensitivity of understorey herbs on these soils. Community mean specific leaf area showed the predicted pattern of less change over time in serpentine than non-serpentine communities.",
            "output": [
                "Are plant communities on infertile soils less sensitive to climate change?"
            ]
        },
        {
            "id": "task847-21b39c1e7cdb4013b1c909309bb49883",
            "input": "Esophageal carcinoma is one of the most aggressive human cancers, and novel treatment modality is required. Although expressing adequate levels of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, significant proportion of esophageal cancer cells exhibit resistance to the cytotoxic effect of this ligand. Licochalcone-A (LA), a flavonoid present in a variety of edible plants, exhibits a wide spectrum of pharmacologic properties such as anticancer, antioxidant, and anti-inflammatory activities.', 'Eca109 and TE1 cells were cultured and transfected, then their viability was detected using MTT assay. Immunoprecipitation and immunoblotting analysis and RT-PCR analysis were also performed.', 'In this study, we found that LA synergistically caused the TRAIL-induced apoptosis in Eca109 and TE1 cells. Such potentiation was achieved through inhibiting Akt activation and promoting proteasomal degradation of X-linked Inhibitor of Apoptosis Protein (XIAP) which mediated the survival signals and allow the cells to escape from apoptosis in various human cancers.",
            "output": [
                "Does licochalcone-A sensitize human esophageal carcinoma cells to TRAIL-mediated apoptosis by proteasomal degradation of XIAP?"
            ]
        },
        {
            "id": "task847-dbea7c66b380429891083937e5514e50",
            "input": "Lymph node metastasis is one of the most important prognostic factors in patients with esophageal squamous cell carcinoma (ESCC). Neoadjuvant treatment can reduce micrometastasis in lymph nodes to enable curative resection by down staging. The aim of this study was to evaluate the histological effect of neoadjuvant therapy on lymph node metastasis of ESCC by performing immunohistochemistry for cytokeratin staining.', 'A total of 3061 lymph nodes were examined from 62 patients who received neoadjuvant treatment followed by esophagectomy with lymphadenectomy.', 'We observed positive staining for cytokeratin in 276 (9.0%) lymph nodes, which included overt metastasis, micrometastasis and hyalinized cytokeratin particles (HCP). Patients with HCPs in lymph nodes had better outcomes than patients without HCPs in lymph node. A significant prognostic difference between the patients with HCPs and without HCPs was observed in a subgroup of patients with nodal metastasis.",
            "output": [
                "Is intranodal cytokeratin particles a predictive marker of efficacy for neoadjuvant therapies in patients with squamous cell carcinoma of the esophagus?"
            ]
        },
        {
            "id": "task847-d5b555bbbb164855b2790f19aea9f1ae",
            "input": "Therapeutic cancer vaccines aim to boost the natural immunity against transformed cancer cells, and a series of adjuvants and co-stimulatory molecules have been proposed to enhance the immune response against weak self-antigens expressed on cancer cells. For instance, a peptide/CpG-based cancer vaccine has been evaluated in several clinical trials and was shown in pre-clinical studies to favor the expansion of effector T versus Tregs cells, resulting in a potent antitumor activity, as compared to other TLR ligands. Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. Importantly, additive or even synergistic effects have been shown upon combined CD1d/NKT agonists and TLR ligands. The aim of the present study is to combine the activation and tumor targeting of activated iNKT, NK and T cells.', 'Activation and tumor targeting of iNKT cells via recombinant \u03b1-galactosylceramide (\u03b1GC)-loaded CD1d-anti-HER2 fusion protein (CD1d-antitumor) is combined or not with OVA peptide/CpG vaccine. Circulating and intratumoral NK and H-2Kb/OVA-specific CD8 responses are monitored, as well as the state of activation of dendritic cells (DC) with regard to activation markers and IL-12 secretion. The resulting antitumor therapy is tested against established tumor grafts of B16 melanoma cells expressing human HER2 and ovalbumin.', 'The combined CD1d/iNKT antitumor therapy and CpG/peptide-based immunization leads to optimized expansion of NK and OVA-specific CD8 T cells (CTLs), likely resulting from the maturation of highly pro-inflammatory DCs as seen by a synergistic increase in serum IL-12. The enhanced innate and adaptive immune responses result in higher tumor inhibition that correlates with increased numbers of OVA-specific CTLs at the tumor site. Antibody-mediated depletion experiments further demonstrate that in this context, CTLs rather than NK cells are essential for the enhanced tumor inhibition.",
            "output": [
                "Does iNKT/CD1d-antitumor immunotherapy significantly increase the efficacy of therapeutic CpG/peptide-based cancer vaccine?"
            ]
        },
        {
            "id": "task847-c8bc5b5a8783414a90e109cc846f8f29",
            "input": "For patients with cystic fibrosis (CF) Pseudomonas aeruginosa infection is a major contributor to progressive lung disease. While colonizing strains are thought to be primarily environmental, which environments are important in lung colonization is unclear.', 'We took 11,674 samples from a broad range of sites over 3-8 visits to homes with (7) and without (8) CF patients.', 'Twenty-eight percent of sampled drains yielded P. aeruginosa at least once, and a general mixed linear model estimated that 6.3% of samples from drains yield P. aeruginosa. This is more than eight times the estimated recovery from any other type of household environment.",
            "output": [
                "Is pseudomonas aeruginosa in CF and non-CF homes found predominantly in drains?"
            ]
        },
        {
            "id": "task847-b88845549c2a422196a6c717c45edf2a",
            "input": "BACKGROUND/AIMs: Pleiotrophin (PTN) have been demonstrated to play an important role in the development of human gastric cancer. However, the prognostic value remains unclear. The aim of this study was to investigate whether expression of PTN has prognostic relevance in human gastric cancer.', 'Immunohistochemistry was used to investigate the expression of PTN proteins in 178 patients with gastric cancer. The level of PTN mRNA in gastric cancer tissues and paratumor tissues were evaluated in 52 paired cases by quantitative real-time polymerase chainreaction(qRT-PCR). Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance.', 'The expression level of PTN in gastric cancer tissues was significantly higher (P<0.001) than those in paratumor tissues according to the immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of PTN was significantly associated with the tumor site (P=0.001), Lauren\u2019s classification (P<0.001),histologic differentiation(P=0.014),depth of invasion(P<0.001), TNM stage (P=0.003),and lymph node metastasis (P=0.002). Moreover, the Cox proportional- hazards regression analysis revealed that the increased expression of PTN was an independent prognostic factor for poor recurrence-free survival(RFS) and overall survival(OS)(both P<0.001).",
            "output": [
                "Is increased expression of pleiotrophin a prognostic marker for patients with gastric cancer?"
            ]
        },
        {
            "id": "task847-b8f5b03e68284d83b5d94753574f660c",
            "input": "The cyclooxygenase-2 (cox-2) pathway is now recognized to be important in human cancer development and progression. The gene for cox-2 carries a common single nucleotide polymorphism, T8473C, located within a potential functional region in the 3'-UTR of cox-2 gene was identified. We have investigated the frequencies of cox-2 genotypes in Tunisian population to determine whether that polymorphism was associated with the risk of nasopharyngeal carcinoma (NPC) in Tunisian population.\", 'One hundred and eighty-nine NPC patients were compared to 237 healthy controls.', 'The cox-2 T8473C polymorphism was significantly associated with NPC (P=0.031). The CC-genotype and C allele were more frequent in control compared to patients group [CC: OR=0.37; P=0.013; 95% CI: 0.17-0.81; C: OR=0.72; P=0.032; 95% CI: 0.53-0.97]. Multivariate logistic regression analyses revealed that the CC-genotype was associated with a significantly decreased risk of NPC (P=0.013). Tumor sizes, histologic grade, presence of primary lymph node metastases, age or sex were not associated with cox-2 genotypes.",
            "output": [
                "Does the CC-genotype of the cyclooxygenase-2 gene associate with decreased risk of nasopharyngeal carcinoma in a Tunisian population?"
            ]
        },
        {
            "id": "task847-b70c36bb20004264a019fcd09cf6e196",
            "input": "To test whether subsensory vibratory noise applied to the sole of the foot using a novel piezoelectric vibratory insole can significantly improve sensation, enhance balance, and reduce gait variability in elderly people, as well as to determine the optimal level of vibratory noise and whether the therapeutic effect would endure and the user's sensory threshold would remain constant during the course of a day.\", 'A randomized, single-blind, crossover study of 3 subsensory noise stimulation levels on 3 days.', 'Balance and gait laboratory.', 'Healthy community-dwelling elderly volunteers (N=12; age, 65-90y) who could feel the maximum insole vibration.', 'A urethane foam insole with the piezoelectric actuators delivering subsensory vibratory noise stimulation to the soles of the feet.', 'Balance, gait, and timed Up and Go (TUG) test.', 'The vibratory insoles significantly improved performance on the TUG test, reduced the area of postural sway, and reduced the temporal variability of walking at both 70% and 85% of the sensory threshold and during the course of a day. Vibratory sensation thresholds remained relatively stable within and across study days.",
            "output": [
                "Does a shoe insole delivering subsensory vibratory noise improve balance and gait in healthy elderly people?"
            ]
        },
        {
            "id": "task847-3258e720a2cf4dbfa9d42f6771c7479c",
            "input": "The role of sleep in the enhancement of motor skills has been studied extensively in adults. We aimed to determine involvement of sleep and characteristics of spindles and slow waves in a motor skill in children.', 'We hypothesized sleep-dependence of skill enhancement and an association of interindividual differences in skill and sleep characteristics.', '30 children (19 females, 10.7 \u00b1 0.8 years of age; mean \u00b1 SD) performed finger sequence tapping tasks in a repeated-measures design spanning 4 days including 1 polysomnography (PSG) night. Initial and delayed performance were assessed over 12 h of wake; 12 h with sleep; and 24 h with wake and sleep. For the 12 h with sleep, children were assigned to one of three conditions: modulation of slow waves and spindles was attempted using acoustic perturbation, and compared to yoked and no-sound control conditions.', 'Mixed effect regression models evaluated the association of sleep, its macrostructure and spindles and slow wave parameters with initial and delayed speed and accuracy.",
            "output": [
                "Do sleep spindle and slow wave frequency reflect motor skill performance in primary school-age children?"
            ]
        },
        {
            "id": "task847-10de1e81d0014da7bb5960490ce57a35",
            "input": "Cenicriviroc is a potent antagonist of the chemokine coreceptors 5 and 2 (CCR5/CCR2) and blocks HIV-1 entry. The CCR5 inhibitor maraviroc has been shown in tissue culture to be able to repel cell-free virions from the cell surface into extracellular space. We hypothesized that cenicriviroc might exhibit a similar effect, and tested this using clinical samples from the Phase IIb study 652-2-202, by measuring rates of intracellular DNA decline. We also monitored viral RNA levels in culture fluids.', 'We infected PM-1 cells with CCR5-tropic HIV-1 BaL in the presence or absence of inhibitory concentrations of cenicriviroc (20 nM) or maraviroc (50 nM) or controls. Viral load levels and p24 were measured by ELISA, quantitative PCR and quantitative real-time reverse transcription PCR at 4 h post-infection. Frozen PBMC DNA samples from 30 patients with virological success in the Phase IIb study were studied, as were early and late reverse transcript levels. Docking studies compared binding between cenicriviroc/CCR5 and maraviroc/CCR5.', 'Unlike maraviroc, cenicriviroc did not cause an increase in the amount of virus present in culture fluids at 4 h compared with baseline. The use of cenicriviroc did, however, result in lower levels of intracellular viral DNA after 4 h. Structural modelling indicates that cenicriviroc binds more deeply than maraviroc to the hydrophobic pocket of CCR5, providing an explanation for the absence of viral rebound with cenicriviroc.",
            "output": [
                "Does the dual CCR5 and CCR2 inhibitor cenicriviroc redistribute HIV into extracellular space : implications for plasma viral load and intracellular DNA decline?"
            ]
        },
        {
            "id": "task847-e6f05ee2402a4e35ae2c7713ef78085e",
            "input": "Cicatricial alopecia is a form of hair loss that causes both cosmetic and psychological concerns. Although tissue expanders are the common approach to reconstruction, no algorithm exists in the literature for this process. In this study, it was aimed to create an algorithm for the reconstruction of lateral scalp alopecias with the goal to achieve better and standardized results.', 'Lateral scalp alopecias were divided into three groups: total lateral alopecia (type I), temporal and sideburn alopecia (type II), and sideburn alopecia (type III). Tissue expanders were placed at the parieto-occipital area in type I defects, parietal area in type II defects, and the temporal region in type III defects. Tissue expanders were used to create flaps that were advanced with 60\u00b0 rotation, 90\u00b0 rotation, and no rotation for type I, II, and III defects, respectively.', 'Fifteen patients were treated with this algorithm. Using this simple approach, we achieved natural, standardized aesthetic results for each patient, all of whom were satisfied with the final results.",
            "output": [
                "Do our experiences on the reconstruction of lateral scalp burn alopecia with tissue expanders?"
            ]
        },
        {
            "id": "task847-942515e38f8e4bafb8eada8fb45372ab",
            "input": "The aim of this study was to review the impact of salvage external beam radiotherapy (EBRT) of postprostatectomy patients with long-term follow-up on biochemical-free recurrence (BFR) and metastatic-free survival, and to describe pathological and clinical predictors of outcome.', 'In the period 1987-2010, 76 postprostatectomy patients with biochemical and clinical recurrence received salvage EBRT. Patients were treated with conformal EBRT and 68 (90%) received a dose of 70 Gy; eight patients (10%) received a dose of 60-64 Gy. No patients received adjuvant or neoadjuvant androgen deprivation therapy in conjunction with salvage EBRT.', 'The median follow-up time after salvage EBRT was 82 months (range 5-192 months). Seventeen patients (22%) developed biochemical recurrence subsequent to postprostatectomy salvage EBRT during the observation time, and the overall 50 and 75 month actuarial BFR rates after salvage EBRT were 84% and 79%, respectively. Seven patients (9%) developed metastatic disease and two patients died of prostate cancer. Independent predictors of biochemical recurrence were seminal vesicle invasion (SVI) in the prostatectomy specimen (p < 0.05) and prostate-specific antigen doubling time (PSADT) of 6 months or less (p = 0.041) before salvage EBRT.",
            "output": [
                "Is prostate-specific antigen doubling time subsequent to radical prostatectomy a predictor of outcome following salvage external beam radiation therapy : a single-centre experience?"
            ]
        },
        {
            "id": "task847-4f754fe27ad541bb9fdd2f8458e8b13d",
            "input": "Hip dislocation in children with cerebral palsy (CP) is a common and severe problem. The Swedish follow-up program for CP (CPUP) includes standardized monitoring of the hips. Migration percentage (MP) is a widely accepted measure of hip displacement. Coxa valga and valgus of the femoral head in relation to the femoral neck can be measured as the head-shaft angle (HSA). We assessed HSA as a risk factor for hip displacement in CP.', 'We analyzed radiographs of children within CPUP from selected regions of Sweden. Inclusion criteria were children with Gross Motor Function Classification System (GMFCS) levels III-V, MP of < 40% in both hips at the first radiograph, and a follow-up period of 5 years or until development of MP > 40% of either hip within 5 years. Risk ratio between children who differed in HSA by 1 degree was calculated and corrected for age, MP, and GMFCS level using multiple Poisson regression.', '145 children (73 boys) with a mean age of 3.5 (0.6-9.7) years at the initial radiograph were included. 51 children developed hip displacement whereas 94 children maintained a MP of < 40%. The risk ratio for hip displacement was 1.05 (p < 0.001; 95% CI 1.02-1.08). When comparing 2 children of the same age, GMFCS level, and MP, a 10-degree difference in HSA results in a 1.6-times higher risk of hip displacement in the child with the higher HSA.",
            "output": [
                "Is head-shaft angle a risk factor for hip displacement in children with cerebral palsy?"
            ]
        },
        {
            "id": "task847-4a94e0dc4c8147c3949458ebbb25572e",
            "input": "Our trauma service recently transitioned from a pulmonary intensive care unit (ICU) service to a surgical ICU (SICU) service. We hypothesized that a newly formed SICU service could provide comparable outcomes to the existing pulmonary ICU service. A specific aim of this study was to compare outcomes of trauma patients admitted to the ICU before and after implementation of a SICU service.', 'We performed a retrospective study of trauma patients admitted to the ICU of our urban, American College of Surgeons- verified, Level 1 trauma center during a 4-year period (2009-2012). Patients managed by the pulmonary ICU service (2009-2010) were compared with patients managed by a SICU service (2011-2012). The primary outcome was mortality, while secondary outcomes included complications (pulmonary, infectious, cardiac, and thromboembolic), hospital and ICU length of stay, ventilator days, and need for reintubation.', 'There were 2,253 trauma patients admitted to the ICU during the study period, 1,124 and 1,129 managed by the pulmonary ICU and SICU services, respectively. When comparing outcomes for SICU and pulmonary ICU patients, there was no difference in mortality (11% vs. 13%, p = 0.41), but patients managed by the SICU service had fewer pulmonary complications (3% vs. 6%, p < 0.001), fewer days on the ventilator (3 vs. 4, p = 0.002), and less often required reintubation after extubation (4% vs. 9%, p < 0.001).",
            "output": [
                "Is implementation of a surgical intensive care unit service associated with improved outcomes for trauma patients?"
            ]
        },
        {
            "id": "task847-75797a21e8bb4fad91ae9bed1193b709",
            "input": "Avoidant personality disorder is characterized by pervasive anxiety, fear of criticism, disapproval, and rejection, particularly in anticipation of exposure to social situations. An important but underexplored question concerns whether anxiety in avoidant patients is associated with an impaired ability to engage emotion regulatory strategies in anticipation of and during appraisal of negative social stimuli.', 'We examined the use of an adaptive emotion regulation strategy, cognitive reappraisal, in avoidant patients. In addition to assessing individual differences in state and trait anxiety levels, self-reported affect as well as measures of neural activity were compared between 17 avoidant patients and 21 healthy control participants both in anticipation of and during performance of a reappraisal task.', 'Avoidant patients showed greater state and trait-related anxiety relative to healthy participants. In addition, relative to healthy participants, avoidant patients showed pronounced amygdala hyper-reactivity during reappraisal anticipation, and this hyper-reactivity effect was positively associated with increasing self-reported anxiety levels.",
            "output": [
                "Does elevated amygdala activity during reappraisal anticipation predict anxiety in avoidant personality disorder?"
            ]
        },
        {
            "id": "task847-419924338fc44f5f9f677a130cd00652",
            "input": "Studies have reported effects of prenatal marijuana exposure (PME) on cognitive and behavioral outcomes. An earlier publication from this study found that PME predicted early onset of marijuana use and frequency of marijuana use at age 14. No study has reported the effects of PME on marijuana use in young adulthood. This is a developmental period when substance use peaks, and by which, initiation of substance use has largely occurred.', 'Subjects were from a longitudinal cohort. Women were interviewed initially in their fourth prenatal month and women and their offspring were followed through 22 years. Significant covariates of offspring marijuana use at 22 years were identified and controlled for using ordinal logistic regression.', 'PME predicted marijuana use in the offspring at 22 years after controlling for significant covariates. Prenatal alcohol exposure, offspring race, gender, and age were also significant predictors, but family history of substance abuse or disorder, and sociodemographic and psychological characteristics of the mother and offspring were not. This association was not moderated by gender or race.",
            "output": [
                "Does prenatal marijuana exposure predict marijuana use in young adulthood?"
            ]
        },
        {
            "id": "task847-f2d660c87deb48b3a71783e4f9a0cd8f",
            "input": "Nuclear apoptosis-inducing factor 1 (NAIF1) could induce apoptosis in gastric cancer cells. Previously, we have reported that the expression of NAIF1 protein is down-regulated in gastric cancer tissues compared with the adjacent normal tissues. However, the role of NAIF1 in gastric cancer cells is not fully understood.', 'The effects of NAIF1 on cell viability were evaluated by MTT and colony formation assays. The ability of cellular migration and invasion were analyzed by transwell assays. The expression levels of targeted proteins were determined by western blot. The relative RNA expression levels were analyzed using quantitative polymerase chain reaction assays. Xenograft experiment was employed to determine the anti-tumor ability of NAIF1 in vivo.', 'The study demonstrates that transient transfection of NAIF1 in gastric cancer cells BGC823 and MKN45 could inhibit the cell proliferation, migration, and invasion of the two gastric cancer cell lines. The tumor size is smaller in NAIF1-overexpressed MKN45 cell xenograft mice than in unexpressed group. Further in-depth analysis reveals that NAIF1 reduces the expression of MMP2 as well as MMP9, and inhibits the activation of FAK, all of which are key molecules involved in regulating cell migration and invasion. In addition, NAIF1 inhibits the expression of c-Jun N-terminal kinase (JNK) by accelerating its degradation through ubiquitin-proteasome pathway. Meanwhile, NAIF1 reduces the mRNA and protein expression of ERK1/2.",
            "output": [
                "Does nAIF1 inhibit gastric cancer cells migration and invasion via the MAPK pathways?"
            ]
        },
        {
            "id": "task847-6ef8a5d2ec8c43d7bd6193736222ab39",
            "input": "Interferon gamma release assays (IGRAs) are widely used to detect pathogen specific cellular immunity. Cytomegalovirus (CMV) is the foremost problematic viral infection in immunocompromised patients such as transplant or HIV infected patients. CMV antibody ELISAs are not able to predict CMV specific cellular immunity during immunosuppression. We developed a CMV specific IGRA comparing synthetic CMV peptides, native lysate and recombinant antigen. In addition, TLR agonists were tested to enhance CMV antigen immunogenicity.', '397 healthy controls (HC) were stratified according to CMV IgM and IgG serostatus and subsequently tested for IFN\u03b3- and IL2-secretion in whole blood after challenge with synthetic, native or recombinant CMV antigens and TLR agonists by ELISA. The selected TLR agonists were lipopolysaccharide (LPS), lipoteichoic acid (LTA), peptidoglycan (PGN), zymosan (Zym), polyinosinic-polycytidylic acid (Poly(I:C)), flagellin (Fla), R848, loxoribine (Lox) and bropirimine (Bro).', 'Synthetic pp65 peptides elicited strong IFN\u03b3 responses in CMV seropositive, but not seronegative HC (6418 vs. 13 pg/ml). Native lysates and recombinant pp65 induced equally high IFN\u03b3 responses in seropositive (35,877 and 26,428 pg/ml) and increased background IFN\u03b3 expression in seronegative HC (43 and 1148 pg/ml). Diagnostic sensitivity and specificity with regard to anti-CMV serology reached 100% for synthetic pp65 and native CMV lysate, but 57% and 100% for recombinant pp65, respectively. TLR agonists LTA and Poly(I:C) augmented IFN\u03b3 responses after challenge with synthetic pp65 peptide, native lysate or recombinant pp65 in seropositive HC. Seronegative HC remained unaffected. IL2 production was negligible compared to IFN\u03b3.",
            "output": [
                "Is cMV specific cytokine release assay in whole blood optimized by combining synthetic CMV peptides and toll like receptor agonists?"
            ]
        },
        {
            "id": "task847-30d4cc3fb2574d60ace08a63def4b441",
            "input": "Although excess alcohol consumption has been believed to cause liver injury, light alcohol consumption (LAC) has been reported to play a protective role against fatty liver in recent studies. However, the association between non-alcoholic fatty liver disease (NAFLD) and LAC in men with metabolic syndrome (MS) is unclear. The aim of this study was to examine the association between NAFLD and LAC in men with MS.', 'Subjects were 1055 men with MS who underwent a regular health check-up and drank less 20\\xa0g/day of alcohol. A distinction was made between non-drinkers and light drinkers and the association between NAFLD and LAC in men with MS was elucidated. NAFLD was referred as fatty liver with alanine aminotransferase (ALT) levels \u226731 IU/L in this study.', 'Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the prevalence of NAFLD were significantly lower in light drinkers than in non-drinkers. Logistic regression analysis showed body mass index (BMI), waist circumference (WC), uric acid (UA), haemoglobin A1c (HbA1c), visceral fat type MS and LAC (odds ratios: 0.654; 95% confidence intervals: 0.473-0.906; <0.05) were significant predictors of the prevalence of NAFLD.",
            "output": [
                "Does light alcohol consumption play a protective role against non-alcoholic fatty liver disease in Japanese men with metabolic syndrome?"
            ]
        },
        {
            "id": "task847-bd48b0742aa04989afd771bc05da5c40",
            "input": "Genomic selection (GS) may improve selection response over conventional pedigree-based selection if markers capture more detailed information than pedigrees in recently domesticated tree species and/or make it more cost effective. Genomic prediction accuracies using 1748 trees and 6932 SNPs representative of as many distinct gene loci were determined for growth and wood traits in white spruce, within and between environments and breeding groups (BG), each with an effective size of Ne \u2248 20. Marker subsets were also tested.', 'Model fits and/or cross-validation (CV) prediction accuracies for ridge regression (RR) and the least absolute shrinkage and selection operator models approached those of pedigree-based models. With strong relatedness between CV sets, prediction accuracies for RR within environment and BG were high for wood (r = 0.71-0.79) and moderately high for growth (r = 0.52-0.69) traits, in line with trends in heritabilities. For both classes of traits, these accuracies achieved between 83% and 92% of those obtained with phenotypes and pedigree information. Prediction into untested environments remained moderately high for wood (r \u2265 0.61) but dropped significantly for growth (r \u2265 0.24) traits, emphasizing the need to phenotype in all test environments and model genotype-by-environment interactions for growth traits. Removing relatedness between CV sets sharply decreased prediction accuracies for all traits and subpopulations, falling near zero between BGs with no known shared ancestry. For marker subsets, similar patterns were observed but with lower prediction accuracies.",
            "output": [
                "Do genomic selection accuracies within and between environments and small breeding groups in white spruce?"
            ]
        },
        {
            "id": "task847-007022af22004c6cb0d4443103995fa8",
            "input": "There is great variability for the type of anaesthesia used during TAVI, with no clear consensus coming from comparative studies or guidelines. We sought to detect regional differences in the anaesthetic management of patients undergoing transcatheter aortic valve implantation (TAVI) in Europe and to evaluate the relationship between type of anaesthesia and in-hospital and 1 year outcome.', 'Between January 2011 and May 2012 the Sentinel European TAVI Pilot Registry enrolled 2807 patients treated via a transfemoral approach using either local (LA-group, 1095 patients, 39%) or general anaesthesia (GA-group, 1712 patients, 61%).', 'A wide variation in LA use was evident amongst the 10 participating countries. The use of LA has increased over time (from a mean of 37.5% of procedures in the first year, to 57% in last 6 months, p<0.01). MI, major stroke as well as in-hospital death rate (7.0% LA vs 5.3% GA, p=0.053) had a similar incidence between groups, confirmed in multivariate regression analysis after adjusting for confounders. Dividing our population in tertiles according to the Log-EuroSCORE we found similar mortality under LA, whilst mortality was higher in the highest risk tertile under GA. Survival at 1 year, compared by Kaplan-Meier analysis, was similar between groups (log-rank: p=0.1505).",
            "output": [
                "Do local and general anaesthesia influence outcome of transfemoral aortic valve implantation?"
            ]
        },
        {
            "id": "task847-db6130c3a15845f68bf476ba45ae3db7",
            "input": "Multidrug resistant (MDR) uropathogens are increasing in prevalence and may contribute to significant morbidity after percutaneous nephrolithotomy (PCNL). We investigate the presence of MDR bacteriuria and occurrence of postoperative infectious complications in patients who underwent PCNL at our institution.', 'Retrospective review was performed of 81 patients undergoing PCNL by a single surgeon (RLS) between 2009 and 2013. Patient demographics, comorbidities, stone parameters on imaging, and microbial data were compiled. MDR organisms were defined as resistant to three or more of the American Urological Association Best Practice Statement antimicrobial classes for PCNL. Postoperative complications were graded by Clavien score and European Association of Urology infection grade. Univariate comparisons were analyzed between patients with and without a postoperative infectious complication. Multivariate logistic regression was performed to determine significant predictor variables for postoperative infectious complications.', 'Of the 81 patients undergoing PCNL, 41/81 (51%) had positive preoperative urine culture, 24/81 (30%) had positive MDR urine culture, and 16/81 (19%) had a postoperative infectious complication. Multivariate analysis revealed a positive preoperative MDR urine culture significantly increased the risk of postoperative infectious complication (odds ratio [OR]=4.89, 95% confidence interval [CI] 1.134-17.8, P=0.016). The presence of more than one access tract during PCNL also predicted for infectious complications (OR=7.5, 95% CI 2.13-26.4, P=0.003) Of the 16 patients with a postoperative infection 3 (18%) had postoperative urine cultures discordant with the preoperative urine cultures.",
            "output": [
                "Does multidrug resistant bacteriuria before percutaneous nephrolithotomy predict for postoperative infectious complications?"
            ]
        },
        {
            "id": "task847-cae3b9416c274bb7a8266ce48c3ae988",
            "input": "Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. However, no data is currently available regarding the association of fibrinogen level with the presence and severity of new-onset coronary atherosclerosis assessed by Gensini score (GS), particularly in Han Chinese with a large sample size.', 'We studied 2288 consecutive, new-onset subjects undergoing coronary angiography with angina-like chest pain. Clinical and laboratory data were collected. Coronary stenotic lesions were considered to be the incidence of coronary atherosclerosis. The severity of coronary stenosis was determined by the GS system. Data indicated that patients with high GS had significantly elevated fibrinogen level (p<0.001). The prevalence and severity of coronary atherosclerosis were dramatically increased according to fibrinogen tertiles. Spearman correlation analysis revealed a positive association between fibrinogen level and GS (r = 0.138, p<0.001). Multivariate logistic regression analysis demonstrated that plasma fibrinogen level was independently associated with high GS (OR = 1.275, 95% CI 1.082-1.502, p = 0.004) after adjusting for potential confounders. Moreover, fibrinogen level was also independently related to the presence of coronary atherosclerosis (fibrinogen tertile 2: OR = 1.192, 95% CI 0.889-1.598, p = 0.241; tertile 3: OR = 2.003, 95% CI 1.383-2.903, p <0.001) and high GS (fibrinogen tertile 2: OR = 1.079, 95% CI 0.833-1.397, p = 0.565; tertile 3: OR = 1.524, 95% CI 1.155-2.011, p = 0.003) in a dose-dependent manner. Receiver-operating characteristic curve analysis showed that the best fibrinogen cut-off value for predicting the severity of coronary stenosis was 3.21 g/L.",
            "output": [
                "Is higher fibrinogen level independently linked with the presence and severity of new-onset coronary atherosclerosis among Han Chinese population?"
            ]
        },
        {
            "id": "task847-c5e5588f27a9467eb4be0ca9f7920b4b",
            "input": "Suboptimal adherence to antiretroviral therapy (ART) is a strong predictor of virologic failure (VF) among people with HIV. Various methods such as patient self-report, pill counts and pharmacy refills have been utilized to monitor adherence. However, there are limited data on the accuracy of combining methods to better predict VF in routine clinical settings. We examined various methods to assess adherence including pill count, medication possession ratio (MPR), and self-reported adherence in order to determine which was most highly associated with VF after > 6 months on ART.', 'We conducted a secondary analysis of data from a case-control study. At enrollment, pharmacy refill data were collected retrospectively from the medical chart, pill counts were completed to derive a pill count adherence ratio (PCAR) and a self-report questionnaire was administered to all participants. Parametric smooth splines and receiver operator characteristic (ROC) analyses were carried out to assess the accuracy of the adherence methods.', '458 patients were enrolled from October 2010 to June 2012. Of these, 158 (34.50%) experienced VF (cases) and 300 (65.50%) were controls. The median (IQR) PCAR was 1.10 (0.99-1.14) for cases and 1.13 (1.08-1.18) for controls (p < 0.0001). The median MPR was 1.00 (0.97-1.07) for cases and 1.03 (0.96-1.07) for controls (p = 0.83). Combination of PCAR and self-reported questions was highly associated with VF.",
            "output": [
                "Is the combination of pill count and self-reported adherence a strong predictor of first-line ART failure for adults in South Africa?"
            ]
        },
        {
            "id": "task847-ca773ded98594213b13f1faf3d5d9e31",
            "input": "Allergic asthma is characterized by inflammation and airway remodeling. Bronchial epithelium is considered a key player in coordinating airway wall remodeling. In mild asthma, the epithelium is damaged and fails to proliferate and to repair, whereas in severe asthma, the epithelium is highly proliferative and thicker. This may be due to different regulatory mechanisms. The purpose of our study was to determine the role of miRNAs in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison with cells obtained from mild asthmatics and healthy controls.', 'Human bronchial epithelial cells (BEC) were isolated by bronchoscopy from bronchial biopsies of healthy donors and patients with mild and severe asthma. MiRNA expression was evaluated using the TaqMan low-density arrays and qRT-PCR. Transfection studies of bronchial epithelial cells were performed to determine the target genes. Cell proliferation was evaluated by BrdU incorporation test.', 'MiR-19a was upregulated in epithelia of severe asthmatic subjects compared with cells from mild asthmatics and healthy controls. Functional studies based on luciferase reporter and Western blot assays suggest that miR-19a enhances cell proliferation of BEC in severe asthma through targeting TGF-\u03b2 receptor 2 mRNA. Moreover, repressed expression of miR-19a increased SMAD3 phosphorylation through TGF-\u03b2 receptor 2 signaling and abrogated BEC proliferation.",
            "output": [
                "Does microRNA-19a enhance proliferation of bronchial epithelial cells by targeting TGF\u03b2R2 gene in severe asthma?"
            ]
        },
        {
            "id": "task847-388e76f5bad44e1a96854ba972a4e2de",
            "input": "Many peripheral biomarkers, including low cholesterol and its fractions, have been examined to identify suicidal behavior. Herein, we assessed serum lipid profile and some proteins putatively associated with suicidal behavior in subjects with mood disorder (bipolar disorder or major depressive disorder) with a recent suicide attempt and with no lifetime history of suicide attempts.', 'Fifty subjects had presented an episode of attempted suicide during the last 15 days, and 36 subjects had no history of any suicide attempt. We measured total cholesterol, HDL, LDL and triglycerides as well as serum leptin, brain-derived neurotrophic factor (BDNF), S100B and C-reactive protein (CRP).', 'Individuals that had attempted suicide presented decreased body mass index (BMI) and waist circumference. After adjusting for these confounders, we found that triglycerides were decreased in attempted suicide subjects. We found no differences among total cholesterol, LDL, and HDL or leptin, S100B, CRP and BDNF.",
            "output": [
                "Are serum triglycerides , but not cholesterol or leptin , decreased in suicide attempters with mood disorders?"
            ]
        },
        {
            "id": "task847-4e6cc0c1c2214b4395d29f62063cbac7",
            "input": "Research evidence supports a positive link between soft drinks and depressive symptoms. However, data thus far are only from Caucasian populations. We investigated whether high levels of consumption of soft drinks were associated with the depressive symptoms among adults in China.', 'A cross-sectional survey was conducted with 3667 adults in Tianjin, China. Dietary intake was assessed using a valid self-administered food frequency questionnaire, and depressive symptoms were assessed with the Zung Self-Rating Depression Scale (SDS), cut-off point of 40, 45 or 50 indicating elevated depressive symptoms.', 'The prevalence of elevated depressive symptoms was 7.6% (SDS \u226550). After adjustments for potentially confounding factors, the odds ratios (95% confidence interval) of having elevated depressive symptoms by increasing levels of soft drink consumption were 1.00, 1.43 (1.01, 2.01) and 2.00 (1.15, 3.37) (p for trend <0.01). Similar relations were observed when SDS \u226540 or 45 were used as a definition of depressive symptoms.",
            "output": [
                "Is soft drink consumption associated with depressive symptoms among adults in China?"
            ]
        },
        {
            "id": "task847-7a09963587b24ae2a50d00bb77c6663e",
            "input": "Acute alcohol intoxication has been found to increase perseverative errors on the Wisconsin Card Sorting Test, a well known neuropsychological index of prefrontal cortical functioning, in both laboratory and naturalistic settings.', 'The present study examined the relationship between levels of alcohol consumption at campus drinking venues and performance of the Iowa Gambling Task (IGT), another neuropsychological test designed to assess prefrontal cortex dysfunction, after controlling for potential confounding variables including habitual alcohol intake (as a proxy for alcohol tolerance), trait impulsivity, and everyday executive functioning.', 'The 49 participants of both genders aged 18 to 30years were recruited at the relevant venues and showed a broad range of blood alcohol concentrations (BACs) from virtually zero (.002%) to .19%. After controlling for demographic variables, habitual use of alcohol and illicit drugs, and frontal lobe related behavioural traits including impulsivity and disinhibition, BAC negatively predicted gambling money won on the last two trial blocks of the IGT.",
            "output": [
                "Is blood alcohol concentration negatively associated with gambling money won on the Iowa gambling task in naturalistic settings after controlling for trait impulsivity and alcohol tolerance?"
            ]
        },
        {
            "id": "task847-51d9a59542ca4359996de62a88b30762",
            "input": "The role of sexual activity on gastroesophageal reflux disease (GERD) is an under-recognized concern of patients, and one rarely assessed by physicians.', 'The objective of this article is to determine the influence of sexual activity on the intraesophageal acid exposure and acid reflux events in GERD patients.', 'Twenty-one patients with the diagnosis of GERD were prospectively enrolled. Intraesophageal pH monitoring was recorded for 48 hours with a Bravo capsule. All patients were instructed to have sexual intercourse or abstain in a random order two hours after the same refluxogenic dinner within two consecutive nights. Patients were requested to have sex in the standard \"missionary position\" and women were warned to avoid abdominal compression. The patients completed a diary reporting the time of the sexual intercourse and GERD symptoms. The percentage of reflux time and acid reflux events were compared in two ways: within 30 and 60 minutes prior to and after sexual intercourse on the day of sexual intercourse and in the same time frame of the day without sexual intercourse.', 'Fifteen of 21 GERD patients were analyzed. The percentage of reflux time and number of acid reflux events did not show a significant difference within the 30- and 60-minute periods prior to and after sexual intercourse on the day of sexual intercourse and on the day without sexual intercourse, as well.",
            "output": [
                "Does sexual activity predispose to reflux episodes in patients with gastroesophageal reflux disease?"
            ]
        },
        {
            "id": "task847-cb23ebff5f164761a56b4820392c9f95",
            "input": "Trauma is the leading cause of injury and death for individuals aged 1-44 years. Up to 8% of the US population participates in winter sports, and although vascular injuries are uncommon in these activities, little is published in this area. We sought to identify the incidence, injury patterns, and outcomes of vascular injuries resulting from winter sports trauma.', 'Patients with winter sports trauma and the subset with vascular injuries were identified by accessing the National Trauma Data Bank querying years 2007-2010. Patients with and without vascular injuries were then compared. Admission variables included transport time, emergency department hypotension (systolic blood pressure < 90), Glasgow Coma Scale \u2264 8, Injury Severity Score \u2265 25, fractures, solid organ injury, and vascular injury. Outcomes were analyzed and associations with vascular injuries were determined.', 'A total of 2,298 patients were identified with winter sports-related trauma and 28 (1.2%) had associated vascular injuries. Overall, the top 3 injuries were head trauma (16.7%), thoracic vertebral fractures (5.5%), and lumbar vertebral fractures (5.1%). The most common associated vascular injures were to the popliteal artery (17.7%), splenic artery (14.7%), and brachial blood vessels (14.7%). In the entire cohort, 1 patient (0.04%) suffered an amputation and 15 patients (0.7%) died. There were no amputations in the vascular injury group. Mortality was 0.6% in patients without a vascular injury compared with 7.1% of those with a vascular injury (P = 0.01).",
            "output": [
                "Is vascular injury associated with increased mortality in winter sports trauma?"
            ]
        },
        {
            "id": "task847-0624b3803a6c446890f21f273382ae06",
            "input": "Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics.', 'We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations.', 'We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N\\xa0=\\xa0610 adults) and the Hutterites (N\\xa0=\\xa0601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N\\xa0=\\xa0450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N\\xa0=\\xa08858) consortium.', 'We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P\\xa0=\\xa01.6\\xa0\u00d7\\xa010(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P\\xa0=\\xa08.9\\xa0\u00d7\\xa010(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values.",
            "output": [
                "Is a common variant in RAB27A gene associated with fractional exhaled nitric oxide levels in adults?"
            ]
        },
        {
            "id": "task847-f7f9345f7d1940b9ad3a4716b8998cb6",
            "input": "Menopausal reduction in estrogen causes increased adipose accumulation, leading many to turn to dietary supplements to prevent and treat such changes. Enhanced adipose mobilization stimulated by some supplements can increase the risk of non-alcoholic fatty liver disease (NAFLD). Cytoprotective and anti-obesity compounds may prevent the lipotoxicity associated with mobilization.', 'A phytochemical blend was tested in aged, ovariectomized rats. Rats were given the AIN-93M basal diet or a diet containing varying doses of phytochemicals with 2.4 IU/g vitamin D [diet 1: 1000 mg/kg genistein (G); diet 2: 500 mg/kg (G), 200 mg/kg resveratrol (R), and 1000 mg/kg quercetin (Q); diet 3: 1000 mg/kg (G), 400 mg/kg (R), and 2000 mg/kg (Q)].', 'Serum free fatty acids and hepatic triglycerides were elevated with diets 2 and 3. Despite this increase, the phytochemical blends did not increase apoptotic, cell repair, or remodeling gene expression. The highest phytochemical dose prevented increases in serum alanine aminotransferase.",
            "output": [
                "Does a dietary phytochemical blend prevent liver damage associated with adipose tissue mobilization in ovariectomized rats?"
            ]
        },
        {
            "id": "task847-af2b52a6ef0e445f9c273267935328c1",
            "input": "The purpose of this study was to investigate the clinical value of real-time three-dimensional transesophageal echocardiography (RT-3D-TEE) for percutaneous transcatheter closure of multiple secundum atrial septal defects (ASDs) using a Chinese domestic occluder device.', 'From July 2008 to September 2011, 37 patients (mean age 28.4 \u00b1 9.7 years; 24 females) with multiple secundum ASDs underwent percutaneous transcatheter closure in our institution with custom-made occluder devices. RT-3D-TEE was used to clarify the diagnosis and to help determine the operation scheme before the procedure, for real-time monitoring and guiding the operation during the procedure, and for evaluating the result shortly after the procedure.', 'The custom-made atrial septal occluders were successfully implanted in 36 patients under RT-3DTEE guidance. Twenty-seven patients were implanted with two devices and 9 patients with a single device. In two patients where the distance between the two defects was less than 7 mm (5.5 mm and 6 mm), double occluder devices were also successfully implanted. One patient underwent surgery for the complication of unstable occluder and increased residual shunt after closure. No other severe complications were observed.",
            "output": [
                "Is real-time three-dimensional transesophageal echocardiography useful for percutaneous closure of multiple secundum atrial septal defects?"
            ]
        },
        {
            "id": "task847-25e29be687ae4a35a2b30d7441954ee0",
            "input": "Child maltreatment is associated with dysregulation of stress-mediating systems and an increased risk of mental and physical health problems. Specifically, disruptions in hypothalamic-pituitary-adrenal (HPA) axis regulation have been reported in maltreated children. The current study investigates whether increased cortisol variability is responsible for inconsistent patterns in the literature.', 'This study modeled cortisol activity over 20 weeks in 187 maltreated and 154 nonmaltreated children (mean = 8.4 years, SD = 1.8 years) in order to capture week-to-week cortisol patterns. Maltreatment was assessed through coding of Department of Human Services records. Children attended an after-school program 1 day per week for 20 weeks, where saliva was collected at the same time each day and subsequently assayed for cortisol.', \"Multiple-group growth curves indicated that maltreated and non-maltreated children differ in longitudinal cortisol patterns. Maltreated children showed higher variance in the initial cortisol levels and slope over time compared to nonmaltreated children, indicating greater between-person variability in the maltreated group. Maltreated children with higher cortisol at the first assessment showed cortisol suppression over time, indicating potential HPA blunting after chronic high cortisol levels. The severity, timing, and number of subtypes of maltreatment predicted individuals' cortisol variability, and both maltreatment status and greater cortisol variability predicted more behavior problems.",
            "output": [
                "Do longitudinal patterns of cortisol regulation differ in maltreated and nonmaltreated children?"
            ]
        },
        {
            "id": "task847-d7e7e14b454c4b59a53876b95eeb7fa1",
            "input": "The relationship between self-reported lifetime traumatic brain injury (TBI) and drug and alcohol use and associated harms was examined using an epidemiological sample of Canadian adolescents.', 'Data were derived from a 2011 population-based cross-sectional school survey, which included 6383 Ontario 9th-12th graders who self-completed anonymous self-administered questionnaires in classrooms. Traumatic brain injury was defined as loss of consciousness for at least 5 minutes or a minimum 1-night hospital stay due to symptoms.', 'Relative to high schoolers without a history of TBI, those who acknowledged having a TBI in their lifetime had odds 2 times greater for binge drinking (5+ drinks per occasion in the past 4 weeks), 2.5 times greater for daily cigarette smoking, 2.9 times greater for nonmedical use of prescription drugs, and 2.7 times greater for consuming illegal drug in the past 12 months. Adolescents with a history of TBI had greater odds for experiencing hazardous/harmful drinking (adjusted odds ratio [aOR] = 2.3), cannabis problems (aOR = 2.4), and drug problems (aOR = 2.1), compared with adolescents who were never injured.",
            "output": [
                "Does substance Use and Related harm Among Adolescents With and Without Traumatic Brain Injury?"
            ]
        },
        {
            "id": "task847-6b1e56d280ca44769bf640a3045f6efe",
            "input": "Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have become key therapeutic agents for non-small cell lung cancer (NSCLC) patients with EGFR mutation, little is known about the efficacy of EGFR-TKIs according to different treatment timings.', 'A total of 1,250 patients with NSCLC were screened for EGFR mutations at a single institution between March 2006 and May 2010. The efficacy of EGFR-TKIs in terms of response rate (RR), progression-free survival (PFS), and overall survival (OS) were compared according to the treatment timing.', 'Among the 437 patients (36.1 %) with EGFR mutation, we analyzed 222 patients who received EGFR-TKI treatment. With a median follow-up duration of 27.5 months (range 8.3-69.2), EGFR-TKI was given to 97 (43.7 %), 109 (49.1 %), and 16 (7.2 %) patients as first-line, second-line, and third-line therapy, respectively. All three groups showed similar RR (71.1, 72.5, and 75.0 %, respectively) to EGFR-TKI (p = 0.802). No significant difference was observed according to treatment timing of EGFR-TKI in terms of PFS (median 10.6, 13.0, and 10.4 months; p = 0.670) and OS (median 20.5, 26.2, and 17.1 months; p = 0.142). The treatment timing of EGFR-TKI still showed no association with PFS or OS after adjusting significant prognostic factors including performance, disease status, and EGFR mutation types.",
            "output": [
                "Is eGFR-TKI effective regardless of treatment timing in pulmonary adenocarcinoma with EGFR mutation?"
            ]
        },
        {
            "id": "task847-57fb7815d39b43f6871be2a1ed871a99",
            "input": "Increasing evidence suggests an association between diabetes and risk of venous thromboembolism (VTE); however, the results are inconsistent. We conducted a systematic review and meta-analysis of all epidemiological evidence to clarify association of diabetes with risk of VTE.', 'We searched MEDLINE and EMBASE to retrieve all relevant articles. Pooled effect estimates were calculated through a random-effects model.', 'Sixteen articles involving 803,627,121 participants and 10,429,227 VTE patients were included. Pooled analysis of all evidence suggested that diabetes was associated with increased risk of VTE (HR, 1.35; 95%CI, 1.17-1.55; p=2.92*10(-5)), with evidence of small-study effect (p=0.024) and heterogeneity (I(2)=87.1%, p<0.001). However, when analysis was restricted to high quality cohort studies, the association remained significantly (HR, 1.36; 95%CI 1.11-1.68; p=0.004), with no evidence of publication bias (p=0.192) and heterogeneity (I(2)=23.2%, p=0.245).",
            "output": [
                "Is diabetes associated with increased risk of venous thromboembolism : a systematic review and meta-analysis?"
            ]
        },
        {
            "id": "task847-2d65adf6e58e4c17a1dc5734a78b063d",
            "input": "Local invasion is a common pattern of spread in uterine cervical squamous cell carcinoma (CSCC). Although transforming growth factor-beta (TGF-\u03b2) facilitates invasion of various types of cancer cells, the role of the TGF-\u03b2 pathway in CSCC is unclear. In this study, we analyzed the role of TGF-\u03b2 signaling in the progression of CSCC.', 'Immunohistochemistry was used to examine the expression of TGF-\u03b2 pathway molecules in 67 CSCC samples with clinicopathological data. Activation of the TGF-\u03b2 pathway was investigated following co-culture of CSCC cells and cervical cancer-associated fibroblasts (CCAFs).', 'Clinicopathological analysis of CSCC samples revealed that prominent expression of TGF-\u03b2 receptor-2 was more frequent in CSCC with lymphovascular space invasion (LVSI) than without LVSI (p < 0.01). Lymph node metastasis was more frequent in cases in which phosphorylated SMAD3 (pSMAD3) was localized exclusively at the boundary of tumor clusters (n = 9, p < 0.05). Recombinant TGF-\u03b21 increased pSMAD3 expression and enhanced cellular invasion (p < 0.005) in CSCC cells, which was attenuated by an inhibitor of the TGF-\u03b2 receptor (p < 0.005). Enhanced pSMAD3 expression and invasion was also observed when conditioned media from CSCC cells co-cultured with CCAFs were administered. Luciferase assays showed that this medium contained a large amount of active TGF-\u03b2. Along with TGF-\u03b2 activation, thrombospondin-1 was upregulated in both CSCC cells and CCAFs, while thrombospondin-1 silencing in either CSCC cells or CCAFs repressed the activity of TGF-\u03b2. Thrombospondin-1 was prominently expressed in cases with pSMAD3 boundary staining (p < 0.05).",
            "output": [
                "Is invasion of uterine cervical squamous cell carcinoma cells facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta?"
            ]
        },
        {
            "id": "task847-3a88d117942a410cadde48d43ca9366d",
            "input": "To determine whether cancer antigen-125 (CA-125) levels are increased in women with endometriosis, especially in those with endometriomas (OMAs), deep infiltrating lesions (DIE), and superficial endometriosis (SUP) compared with controls without endometriosis in a large cohort of operated women.', 'Cross-sectional study (Canadian Task Force classification II-2).', 'Tertiary-care university hospital.', 'Four hundred six women with histologically proven endometriosis and 279 women without endometriosis.', 'Surgical examination of the abdomino-pelvic cavity.', 'Preoperative serum CA-125 antigen levels were evaluated by electrochemoluminescence immunoassay in women with endometriosis and controls. Correlations between serum CA-125 levels and clinical and anatomical characteristics of disease severity were examined. Women with endometriosis displayed higher mean serum CA-125 levels compared with disease-free controls (50.1\\xa0\u00b1\\xa062.4 U/mL vs 22.5\\xa0\u00b1\\xa025.2 U/mL; p\\xa0\u2264\\xa0.001). CA-125 levels were significantly increased in women with OMA (60.8\\xa0\u00b1\\xa063.5 U/mL) and DIE (55.2\\xa0\u00b1\\xa068.7 U/mL) compared with women with SUP (23.2\\xa0\u00b1\\xa024.5 U/mL) and controls (22.5\\xa0\u00b1\\xa025.2 U/mL). There was no difference in CA-125 levels between patients with SUP and controls and between patients with OMA and DIE. CA-125 serum levels were correlated with DIE severity: the mean number of DIE lesions and worst DIE lesion.",
            "output": [
                "Is increased serum cancer antigen-125 a marker for severity of deep endometriosis?"
            ]
        },
        {
            "id": "task847-a700c076149d4765bf149c4010b52cff",
            "input": "We examined the phenotype and function of lymphocytes collected from the peripheral blood (PBL) and tumor (TIL) of patients with two different solid malignancies: colorectal cancer liver metastases (CRLM) and ovarian cancer (OVC).', 'Tumor and corresponding peripheral blood were collected from 16 CRLM and 22 OVC patients; immediately following resection they were processed and analyzed using a multi-color flow cytometry panel. Cytokine mRNA from purified PBL and TIL CD4(+) T cells were also analyzed by qPCR.', 'Overall, we found similar changes in the phenotypic and cytokine profiles when the TIL were compared to PBL from patients with two different malignancies. The percentage of Treg (CD4(+)/CD25(+)/FoxP3(+)) in PBL and TIL was similar: 8.1% versus 10.2%, respectively in CRLM patients. However, the frequency of Treg in primary OVC TIL was higher than PBL: 19.2% versus 4.5% (p <0.0001). A subpopulation of Treg expressing HLA-DR was markedly increased in TIL compared to PBL in both tumor types, CRLM: 69.0% versus 31.7% (p = 0.0002) and OVC 74.6% versus 37.0% (p <0.0001), which suggested preferential Treg activation within the tumor. The cytokine mRNA profile showed that IL-6, a cytokine known for its immunosuppressive properties through STAT3 upregulation, was increased in TIL samples in patients with OVC and CRLM. Both TIL populations also contained a significantly higher proportion of activated CD8(+) T cells (HLA-DR(+)/CD38(+)) compared to PBL (CRLM: 30.2% vs 7.7%, (p = 0.0012), OVC: 57.1% vs 12.0%, (p <0.0001)).",
            "output": [
                "Do detailed characterization of tumor infiltrating lymphocytes in two distinct human solid malignancies show phenotypic similarities?"
            ]
        },
        {
            "id": "task847-01cd2fd7fcd840a9a3df0ebf60aee1ad",
            "input": "Retrospective evaluation of the long-term health-related quality of life (HRQoL) among survivors after non-small-cell lung cancer (NSCLC) surgery.', 'A total of 586 patients underwent surgery for NSCLC in Helsinki University Central Hospital between January 2000 and June 2009. Two validated quality-of-life questionnaires, the 15D and the EORTC QLQ-C30 with its lung cancer-specific module, QLQ-LC13, were sent to the 276 patients alive in June 2011. Response rate was 83.3%. Results of the 15D were compared with those of an age- and gender-standardized general population.', 'Median follow-up was 5 years. Compared with a general population, our patients had a significantly lower 15D total score, representing their total HRQoL and scores for dimensions of mobility, breathing, usual activities, depression, distress, and vitality. The patients, however, scored significantly higher on vision, hearing, and mental function.",
            "output": [
                "Do long-term lung cancer survivors have permanently decreased quality of life after surgery?"
            ]
        },
        {
            "id": "task847-afbc637428e74890ad087b051a4c5851",
            "input": "The aim of this study was to evaluate the effects of maternal obesity on pancreas structure and carbohydrate metabolism in early adult life, focusing on the F1 and F2 generations after F0 maternal pregestational, gestation, and lactation high-fat diet (HF).', 'C57 BL/6 female mice (F0) were fed standard chow (SC) or an HF diet for 8 wk before mating and during the gestation and lactation periods to provide the F1 generation (F1-SC and F1-HF). At 3 mo old, F1 females were mated to produce the F2 generation (F2-SC and F2-HF). The male offspring from all groups were evaluated at 3 mo old.', 'F0-HF and F1-HF dams were overweight before gestation and had a higher body mass gain and energy intake during gestation, although only F0-HF dams presented pregestational hyperglycemia. The F1-HF offspring had higher body mass, energy intake, fasting glucose levels, and were glucose intolerant compared with F1-SC offspring. These parameters were not significantly altered in F2-HF offspring. Both F1-HF and F2-HF offspring showed hyperinsulinemia, hyperleptinemia, decreased adiponectin levels, increased pancreatic mass, and islet volume density with elevated \u03b1- and \u03b2-cell mass, hypertrophied islet characterized by an altered distribution of \u03b1- and \u03b2-cells and weak pancreatic-duodenal homeobox (Pdx)1 immunoreactivity.",
            "output": [
                "Does pregestational maternal obesity impair endocrine pancreas in male F1 and F2 progeny?"
            ]
        },
        {
            "id": "task847-3b680cf163b546e1b312f0dbfdece86e",
            "input": "In a recent clinical trial, patients with newly diagnosed glioblastoma multiforme benefited from chloroquine (CQ) in combination with conventional therapy (resection, temozolomide [TMZ], and radiation therapy). In the present study, the authors report the mechanism by which CQ enhances the therapeutic efficacy of TMZ to aid future studies aimed at improving this therapeutic regimen.', 'Using in vitro and in vivo experiments, the authors determined the mechanism by which CQ enhances TMZ cytotoxicity. They focused on the inhibition-of-autophagy mechanism of CQ by knockdown of the autophagy-associated proteins or treatment with autophagy inhibitors. This mechanism was tested using an in vivo model with subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ.', 'Knockdown of the autophagy-associated proteins (GRP78 and Beclin) or treatment with the autophagy inhibitor, 3-methyl adenine (3-MA), blocked autophagosome formation and reduced CQ cytotoxicity, suggesting that autophagosome accumulation precedes CQ-induced cell death. In contrast, blocking autophagosome formation with knockdown of GRP78 or treatment with 3-MA enhanced TMZ cytotoxicity, suggesting that the autophagy pathway protects from TMZ-induced cytotoxicity. CQ in combination with TMZ significantly increased the amounts of LC3B-II (a marker for autophagosome levels), CHOP/GADD-153, and cleaved PARP (a marker for apoptosis) over those with untreated or individual drug-treated glioma cells. These molecular mechanisms seemed to take place in vivo as well. Subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ displayed higher levels of CHOP/GADD-153 than did untreated or individual drug-treated tumors.",
            "output": [
                "Does chloroquine enhance temozolomide cytotoxicity in malignant gliomas by blocking autophagy?"
            ]
        },
        {
            "id": "task847-6d4303c67709495b98082169c2ff6127",
            "input": "The objective of this study was to report the authors' experience with the long-term administration of temozolomide (TMZ; > 6 cycles, up to 101) in patients with newly diagnosed glioblastoma and to analyze its feasibility and safety as well as its impact on survival. The authors also compared data obtained from the group of patients undergoing long-term TMZ treatment with data from patients treated with a standard TMZ protocol.\", 'A retrospective analysis was conducted of 37 patients who underwent operations for glioblastoma between 2004 and 2012. Volumetric analysis of postoperative Gd-enhanced MR images, obtained within 48 hours, confirmed tumor gross-total resection (GTR) in all but 2 patients. All patients received the first cycle of TMZ at a dosage of 150 mg/m(2) starting on the second or third postsurgical day. Afterward, patients received concomitant radiochemotherapy according to the Stupp protocol. With regard to adjuvant TMZ therapy, the 19 patients in Group A, aged 30-72 years (mean 56.1 years), received 150 mg/m(2) for 5 days every 28 days for more than 6 cycles (range 7-101 cycles). The 18 patients in Group B, aged 46-82 years (mean 64.8 years), received the same dose, but for no more than 6 cycles. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was analyzed for both groups and correlated with overall survival (OS) and progression-free survival (PFS). The impact of age, sex, Karnofsky Performance Scale score, and Ki 67 staining were also considered.', 'All patients but 1 in Group A survived at least 18 months (range 18-101 months), and patients in Group B survived no more than 17 months (range 2-17 months). The long-term survivors (Group A), defined as patients who survived at least 12 months after diagnosis, were 51.3% of the total (19/37). Kaplan-Meier curve analysis showed that patients treated with more than 6 TMZ cycles had OS and PFS that was significantly longer than patients receiving standard treatment (median OS 28 months vs 8 months, respectively; p = 0.0001; median PFS 20 months vs 4 months, respectively; p = 0.0002). By univariate and multivariate Cox proportional hazard regression analysis, MGMT methylation status and number of TMZ cycles appeared to be survival prognostic factors in patients with glioblastoma. After controlling for MGMT status, highly significant differences related to OS and PFS between patients with standard and long-term TMZ treatment were still detected. Furthermore, in Group A and B, the statistical correlation of MGMT status to the number of TMZ cycles showed a significant difference only in Group A patients, suggesting that MGMT promoter methylation was predictive of response for long-term TMZ treatment. Prolonged therapy did not confer hematological toxicity or opportunistic infections in either patient group.",
            "output": [
                "Is long-term therapy with temozolomide a feasible option for newly diagnosed glioblastoma : a single-institution experience with as many as 101 temozolomide cycles?"
            ]
        },
        {
            "id": "task847-4f31d1e2a403406a8cf9e49bdcc3e04e",
            "input": "Hyponatraemia is a common, potentially life-threatening, complication of thiazide diuretics. The mechanism of thiazide-induced hyponatraemia is incompletely understood. Previous experiments have suggested a direct effect of thiazide diuretics on the plasma membrane expression of aquaporin (AQP)2.', 'We examined the effects of a single re-exposure to hydrochlorothiazide (HCTZ) 50\\u200amg on water balance, renal sodium handling and osmoregulation in 15 elderly hypertensive patients with a history of thiazide-induced hyponatraemia and 15 matched hypertensive controls using thiazide diuretics without previous hyponatraemia.', 'Patients with thiazide-induced hyponatraemia had significantly lower body weight and lower plasma sodium and osmolality at baseline. After HCTZ administration, plasma sodium and osmolality significantly decreased and remained lower in patients compared with controls (P\\u200a<\\u200a0.001). Plasma antidiuretic hormone (ADH) and urine AQP2 were low or suppressed in patients, whereas solute and electrolyte-free water clearance was significantly increased compared with controls. Ad libitum water intake was significantly higher in patients (2543\\u200a\u00b1\\u200a925\\u200aml) than in controls (1828\\u200a\u00b1\\u200a624\\u200aml, P\\u200a<\\u200a0.05), whereas urinary sodium excretion did not differ. In contrast, urea excretion remained significantly lower in patients (263\\u200a\u00b1\\u200a69\\u200ammol per 24\\u200ah) compared with controls (333\\u200a\u00b1\\u200a97\\u200ammol per 24\\u200ah, P\\u200a<\\u200a0.05) and predicted the decrease in plasma sodium following HCTZ administration.",
            "output": [
                "Is thiazide-induced hyponatraemia associated with increased water intake and impaired urea-mediated water excretion at low plasma antidiuretic hormone and urine aquaporin-2?"
            ]
        },
        {
            "id": "task847-9f37a559fdc74c4c8b952de8bb5a1816",
            "input": "Achievement of early therapeutic anticoagulation with unfractionated heparin (UFH) is associated with improved outcomes in thromboembolic disease. Weight based UFH expedites time to therapeutic anticoagulation. Treatment with UFH is challenging in surgical patients due to their high propensity for bleeding. We sought to test the hypothesis that an initial weight based UFH infusion in surgical patients increases the percentage of patients who achieve early therapeutic anticoagulation without increasing the risk of hemorrhagic events.', 'Using a non-concurrent retrospective cohort study design, adult surgical patients receiving UFH for venous thromboembolism (VTE) at a tertiary care center were included. Two groups were identified: the weight based (WB) and the under-dosed (UD) heparin groups. For our primary outcome, we compared percentage of patients in each group that achieved a therapeutic PTT within 24\\xa0h. Secondary outcomes included the incidence of supratherapeutic PTT levels, hemorrhagic events, and complications associated with VTE.', '73 subjects met study criteria, which included 8 subjects in the WB group and 65 in the UD group. The demographic, baseline laboratory, admitting service and type of VTE were similar between the 2 groups. The percentages of WB and UD subjects who achieved a therapeutic PTT within 24\\xa0h were 75% and 28%, respectively (p\\xa0<\\xa00.01). There was no difference in the incidence of supratherapeutic PTT or hemorrhagic events.",
            "output": [
                "Is weight based heparin dosing for thromboembolic disease associated with earlier anticoagulation in surgical patients?"
            ]
        },
        {
            "id": "task847-3fcb2d7eab814db59f156a182f4ba7eb",
            "input": "The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET).', 'Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually.', 'Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET.",
            "output": [
                "Does prospective international cohort study demonstrate inability of interim PET to predict treatment failure in diffuse large B-cell lymphoma?"
            ]
        },
        {
            "id": "task847-283ba48337c84d478cb2f5b02a36e5c5",
            "input": "Myriocin is a fungal metabolite with antiviral activity, including influenza, hepatitis B, and hepatitis C viruses. We investigated whether myriocin has activity against human HSV-2, one of the most prevalent pathogens of sexually transmitted disease.', 'Cell culture systems were used to evaluate myriocin effect on HSV-2 infection. Plaque forming assay and immunoblotting studies were used to determine virus production and viral protein expression, respectively.', 'Myriocin showed no cytotoxic effect at up to 5 \u03bcM. Myriocin treatment did not inhibit HSV-2 infection. Instead, the treatment resulted in accelerated replication of HSV-2 and increased titers of infectious virion. The effect was detected at concentrations as low as 3 nM and plateaued at approximately 30 nM. Myriocin at 30 nM increased HSV-2 production by approximately 1.7 logs. Myriocin also promoted HSV-1 infection but required higher concentrations. A time course study revealed that myriocin promoted HSV-2 infection by acceleration of virus replication. Unlike trichostatin A that promotes HSV-2 infection and histone modifications, myriocin treatment did not alter histone modifications. Myriocin is a well characterized inhibitor of sphingolipid biosynthesis pathway. Structurally different inhibitors of the pathway showed no effect on HSV-2 infection. Exogenous sphingolipids did not reverse the effect of myriocin on HSV-2 infection either.",
            "output": [
                "Does fungal metabolite myriocin promote human herpes simplex virus-2 infection?"
            ]
        },
        {
            "id": "task847-7bb8a8e9b1214298abae0b2234c1c0aa",
            "input": "Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 \u03bcg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session.', 'We prenatally exposed Wistar rats to LPS (100 \u03bcg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed.', 'Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS.",
            "output": [
                "Does prenatal zinc reduce stress response in adult rat offspring exposed to lipopolysaccharide during gestation?"
            ]
        },
        {
            "id": "task847-d12110acb1f6479aa0d6037201abe9c4",
            "input": "Alterations in epigenetic processes are frequently noted in human disease. These epigenetic processes involve methylation of DNA and post-translational modifications of histones. It is well established that in particular histone methylation plays a key role in gene transcription. In this study, we have investigated the relationship between triple methylation of lysine 27 in histone H3 (H3K27Me3) modifications and atherosclerotic plaque stage.', '28 peri-renal aortic tissue patches covering the entire spectrum of atherosclerotic plaque development were evaluated by immunohistochemistry for the levels of H3K27Me3, EZH2, JMJD3 and BMI1.', 'The results of our studies are in support of a reduction in global levels of the H3K27Me3 modification in vessels with advanced atherosclerotic plaques. This reduction in H3K27Me3 levels is not accompanied by alterations in global levels of the corresponding histone methyltransferase EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2). Likewise no alterations in global levels of BMI1, a component of the PRC1 complex, which binds to H3K27Me3-modified histones or the global expression levels of the histone demethylase JMJD3, which removes the methyl marks on H3K27, were observed.",
            "output": [
                "Are global histone H3 lysine 27 triple methylation levels reduced in vessels with advanced atherosclerotic plaques?"
            ]
        },
        {
            "id": "task847-fa176969048744bcab15e61bb450f949",
            "input": "Despite recent advances in prostate cancer diagnostics and therapeutics, the overall survival rate still remains low. This study was aimed to assess potential anti-cancer activity of maysin, a major flavonoid of corn silk (CS, Zea mays L.), in androgen-independent human prostate cancer cells (PC-3).', 'Maysin was isolated from CS of Kwangpyeongok, a Korean hybrid corn, via methanol extraction and preparative C18 reverse phase column chromatography. Maysin cytotoxicity was determined by either monitoring cell viability in various cancer cell lines by MTT assay or morphological changes. Apoptotic cell death was assessed by annexin V-FITC/PI double staining, depolarization of mitochondrial membrane potential (MMP), expression levels of Bcl-2 and pro-caspase-3 and by terminal transferase mediated dUTP-fluorescein nick end labeling (TUNEL) staining. Underlying mechanism in maysin-induced apoptosis of PC-3 cells was explored by evaluating its effects on Akt and ERK pathway.', 'Maysin dose-dependently reduced the PC-3 cell viability, with an 87% reduction at 200 \u03bcg/ml. Maysin treatment significantly induced apoptotic cell death, DNA fragmentation, depolarization of MMP, and reduction in Bcl-2 and pro-caspase-3 expression levels. Maysin also significantly attenuated phosphorylation of Akt and ERK. A combined treatment with maysin and other known anti-cancer agents, including 5-FU, etoposide, cisplatin, or camptothecin, synergistically enhanced PC-3 cell death.",
            "output": [
                "Does corn silk maysin induce apoptotic cell death in PC-3 prostate cancer cells via mitochondria-dependent pathway?"
            ]
        },
        {
            "id": "task847-4a1e0a97219142488dfae945efa28e97",
            "input": "Strychnos spinosa Lam. is a deciduous tree used in traditional medicine to treat infectious diseases. This study is designed to determine the antimicrobial, antioxidant and cytotoxic activities of extracts and fractions from leaves of S. spinosa.', 'Extracts were obtained by maceration with acetone, methanol and dichloromethane/methanol (1/1) while fractions were prepared by liquid-liquid fractionation of the acetone extract. A broth serial microdilution method with tetrazolium violet as growth indicator was used to determine the minimum inhibitory concentration (MIC) against fungi, Gram-positive and Gram-negative bacteria. The antioxidant activity was determined using free-radical-scavenging assays, and the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide reduction assay was used to determine cytotoxicity.', 'Four extracts and five fractions had good to weak antimicrobial activity with MICs ranging from 0.04 to >1.25\\xa0mg/ml against both fungi and bacteria. The chloroform and ethyl acetate fractions had an MIC of 0.08\\xa0mg/ml against Aspergillus fumigatus. The n-butanol fraction had an MIC of 0.04\\xa0mg/ml against Cryptococcus neoformans. The hexane and chloroform fractions had an MIC of 0.08\\xa0mg/ml against Staphylococcus aureus. The antioxidant activities were much lower than that of the positive controls. Except for the alkaloid extract, all the extracts and fractions had free-radical-scavenging activity (IC50 ranging from 33.66 to 314.30\\xa0\u03bcg/ml). The cytotoxicity on Vero cells was reasonable to low with LC50 values ranging between 30.56 and 689.39\\xa0\u03bcg/ml.",
            "output": [
                "Do some Strychnos spinosa ( Loganiaceae ) leaf extracts and fractions have good antimicrobial activities and low cytotoxicities?"
            ]
        },
        {
            "id": "task847-7f13d672537747f3bf2c9bf90113378c",
            "input": "Sickness during pregnancy is associated with an increased risk of offspring neurodevelopmental disorders. Rodent models have played a critical role in establishing causal relationships and identifying mechanisms of altered brain and behavior development in pups prenatally exposed to maternal immune activation (MIA). We recently developed a novel nonhuman primate model to bridge the gap between human epidemiological studies and rodent models of prenatal immune challenge. Our initial results demonstrated that rhesus monkeys given the viral mimic synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-l-lysine) during pregnancy produce offspring with abnormal repetitive behaviors, altered communication, and atypical social interactions.', 'We utilized noninvasive infrared eye tracking to further evaluate social processing capabilities in a subset of the first trimester MIA-exposed offspring (n = 4) and control animals (n = 4) from our previous study.', 'As juveniles, the MIA offspring differed from control animals on several measures of social attention, particularly when viewing macaque faces depicting the fear grimace facial expression. Compared with control animals, MIA offspring had a longer latency before fixating on the eyes, had fewer fixations directed at the eyes, and spent less total time fixating on the eyes of the fear grimace images.",
            "output": [
                "Does maternal immune activation in nonhuman primates alter social attention in juvenile offspring?"
            ]
        },
        {
            "id": "task847-f90035c67ad2441187db6adcd33da546",
            "input": "Atractylodes macrocephala Koidz (AMK), a valuable traditional Chinese herbal medicine, has been widely used in clinical practice for treating patients with disorders of the digestive system. AMK has shown noteworthy promoting effect on improving gastrointestinal function and immunity, which might represent a promising candidate for the treatment of intestinal mucosa injury. The aim of this study was to investigate the efficacy of AMK on intestinal mucosal restitution and the underlying mechanisms via intestinal epithelial (IEC-6) cell migration model.', 'A cell migration model of IEC-6 cells was induced by a single-edge razor blade along the diameter of the cell layers in six-well polystyrene plates. After wounding, the cells were grown in control cultures and in cultures containing spermidine (5\u03bcM, SPD, reference drug), alpha-difluoromethylornithine (2.5mM, DFMO, polyamine inhibitor), AMK (50, 100, and 200mg/L), DFMO plus SPD and DFMO plus AMK for 12h. The polyamines content was detected by high-performance liquid chromatography (HPLC) with pre-column derivatization. The Rho mRNAs expression levels were assessed by Q-RT-PCR. The Rho and non-muscle myosin II proteins expression levels were analyzed by Western blot. The formation and distribution of non-muscle myosin II stress fibers were monitored with immunostaining techniques using specific antibodies and observed by confocal microscopy. Cell migration assay was carried out using inverted microscope and the Image-Pro Plus software. All of these indexes were used to evaluate the effectiveness of AMK.', '(1) Treatment with AMK caused significant increases in cellular polyamines content and Rho mRNAs and proteins expression levels, as compared to control group. Furthermore, AMK exposure increased non-muscle myosin II protein expression levels and formation of non-muscle myosin II stress fibers, and resulted in an acceleration of cell migration in IEC-6 cells. (2) Depletion of cellular polyamines by DFMO resulted in a decrease of cellular polyamines levels, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, thereby inhibiting IEC-6 cell migration. AMK not only reversed the inhibitory effects of DFMO on the polyamines content, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, but also restored cell migration to control levels.",
            "output": [
                "Does atractylodes macrocephala Koidz stimulate intestinal epithelial cell migration through a polyamine dependent mechanism?"
            ]
        },
        {
            "id": "task847-0bdec751a416425a845b8efb9e76ee02",
            "input": "Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. However, the underlying mechanisms are not fully understood. Accumulating evidence shows that the elevated vascular tone in hypertension is a consequence of the 'ion channel remodelling' that occurs during sustained high BP. The present study investigated the effects of aerobic exercise on the electrical remodelling of L-type Ca(2+) (Cav 1.2) and large-conductance Ca(2+) -activated K(+) (KCa 1.1) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHRs).\", 'SHRs and normotensive (Wistar-Kyoto) rats were subjected to aerobic training or kept sedentary, and vascular mechanical and functional properties were evaluated.', 'Exercise did not affect the heart weight, but reduced the heart rate and body weight in SHR. In mesenteric arterial myocytes, exercise normalized the increased Cav 1.2 and KCa 1.1 current density in SHRs. Exercise also ameliorated the increased open probability and mean open time of the single KCa 1.1 channel in hypertension. The isometric contraction study revealed that both nifedipine (Cav 1.2 channel blocker) and NS11021 (KCa 1.1 channel activator) induced concentration-dependent vasorelaxation in MAs precontracted with noradrenaline. Exercise normalized the increased sensitivity of tissues to nifedipine and NS11021 in SHR. Furthermore, protein expression of the Cav 1.2 \u03b11C -subunit together with the KCa 1.1 \u03b1- and \u03b21-subunit was significantly increased in SHRs; and exercise ameliorated these molecular alterations in hypertension.",
            "output": [
                "Does chronic exercise normalize changes in Cav 1.2 and KCa 1.1 channels in mesenteric arteries from spontaneously hypertensive rats?"
            ]
        },
        {
            "id": "task847-2e24fbbcd93642618e22ff02e08c4e7e",
            "input": "The chemokine receptor CXCR3 is implicated in a variety of clinically important diseases, notably rheumatoid arthritis and atherosclerosis. Consequently, antagonists of CXCR3 are of therapeutic interest. In this study, we set out to characterize binding sites of the specific low MW CXCR3 antagonist VUF10085 and the broad spectrum antagonist TAK-779 which blocks CXCR3 along with CCR2 and CCR5.', 'Molecular modelling of CXCR3, followed by virtual ligand docking, highlighted several CXCR3 residues likely to contact either antagonist, notably a conserved aspartate in helix 2 (Asp-112(2:63) ), which was postulated to interact with the quaternary nitrogen of TAK-779. Validation of modelling was carried out by site-directed mutagenesis of CXCR3, followed by assays of cell surface expression, ligand binding and receptor activation.', 'Mutation of Asn-132(3.33) , Phe-207 and Tyr-271(6.51) within CXCR3 severely impaired both ligand binding and chemotactic responses, suggesting that these residues are critical for maintenance of a functional CXCR3 conformation. Contrary to our hypothesis, mutation of Asp-112(2:63) had no observable effects on TAK-779 activity, but clearly decreased the antagonist potency of VUF 10085. Likewise, mutations of Phe-131(3.32) , Ile-279(6.59) and Tyr-308(7.43) were well tolerated and were critical for the antagonist activity of VUF 10085 but not for that of TAK-779.",
            "output": [
                "Does cXCR3 antagonist VUF10085 bound to an intrahelical site distinct from that of the broad spectrum antagonist TAK-779?"
            ]
        },
        {
            "id": "task847-2bf345dbf5574ee581d5af37d4b93850",
            "input": "Prolonged P wave duration is a marker of delayed inter-atrial conduction which may predict cardiovascular disease (CVD). Type 2 diabetes is a risk factor for all atherosclerotic manifestations including stroke. We evaluated the prognostic significance of prolonged P wave duration among middle-aged Finnish type 2 diabetes patients with and without prevalent non-major macrovascular disease (PNMMVD) with respect to total and stroke mortality.', 'We followed up for 18 years 739 type 2 diabetic patients without previous major CVD event at baseline. Participants were stratified according to P wave duration (<114 or \u2265 114 ms) and PNMMVD (i.e. coronary heart disease defined as ischaemic ECG changes and typical symptoms of angina pectoris, or claudication; yes or no). The Cox proportional hazards model was used to estimate the joint association between P wave duration, PNMMVD and the mortality risk.', 'During the follow-up, 509 patients died, and 59 of them died from stroke. Those who had prolonged P wave duration had 2.45 (95% confidence interval: 1.11-5.37) increased stroke mortality among PNMMVD patients. In patients without PNMMVD, there was no relationship between P wave duration and stroke mortality.",
            "output": [
                "Does prolonged P wave duration predict stroke mortality among type 2 diabetic patients with prevalent non-major macrovascular disease?"
            ]
        },
        {
            "id": "task847-b5cefce7775b42f5837096c8ac7cea9d",
            "input": "The present study aimed to investigate the intraplantar (ipl) and central (icv) effects of neuropeptide S (NPS) in the formalin test and to evaluate the role of adenosine receptors, mainly A1 and A2A, in mediating such effects.', 'The ipl injection of formalin was used to assess the nociceptive activity. Moreover, by pretreating mice with non-selective and selective antagonists of adenosine receptors, the effects of icv NPS on formalin-induced ongoing nociception were assessed.', 'Morphine-induced antinociceptive effects were observed during phases 1 and 2 of the test, while indomethacin was active only at the later nociceptive phase. The ipl injection of NPS (alone or combined with formalin) did not modify the nociceptive response. However, icv NPS significantly reduced formalin-induced nociception during both phases. Caffeine (3 mg/kg, ip), a non-selective adenosine receptor antagonist, prevented NPS-induced antinociceptive effects. Similar to caffeine, icv ZM241385 (0.01 nmol), an A2A receptor antagonist, prevented the antinociceptive effects of NPS. Moreover, icv DPCPX (0.001 nmol), an A1 receptor antagonist, blocked the effects of NPS only during phase 1.",
            "output": [
                "Do central adenosine A1 and A2A receptors mediate the antinociceptive effects of neuropeptide S in the mouse formalin test?"
            ]
        },
        {
            "id": "task847-27386cd658e6438d9b6c206633aae9bc",
            "input": "Diabetes mellitus (DM) is frequently associated with peripheral and central complications and has recently emerged as a risk factor for cognitive impairment and dementia. Kynurenic acid (KYNA), a unique tryptophan derivative, displays pleiotropic effects including blockade of ionotropic glutamate and \u03b17 nicotinic receptors. Here, the influence of experimental diabetes on KYNA synthesis was studied in rat brain.', 'DM was induced by i.p. administration of streptozotocin (STZ). Five weeks later, KYNA content and the activity of semi-purified kynurenine aminotransferases (KATs) were measured in frontal cortex, hippocampus and striatum of diabetic and insulin-treated rats, using HPLC-based methods.', 'Hippocampal but not cortical or striatal KYNA concentration was considerably increased during DM, either untreated or treated with insulin (220% and 170% of CTR, respectively). The activity of kynurenine aminotransferase I (KAT I) was not affected by DM in all of the studied structures. KAT II activity was moderately increased in cortex (145% of CTR) and hippocampus (126% of CTR), but not in striatum of diabetic animals. Insulin treatment normalized cortical but not hippocampal KAT II activity.",
            "output": [
                "Does experimental diabetes mellitus type 1 increase hippocampal content of kynurenic acid in rats?"
            ]
        },
        {
            "id": "task847-069481a657ad4b3bba9ea801f05f046f",
            "input": "Gastrointestinal dysfunction is one of the major complications of diabetes. The roles of inflammation in diabetes and its associated complications are increasingly recognized. p38 mitogen-activated protein kinase (MAPK) has been shown to be involved in the production of pro-inflammatory mediators. The aims of this study were to investigate the effects of SB203580, a specific p38 MAPK inhibitor, on delayed gastric emptying in diabetic rats and to elucidate its possible mechanism.', 'SB203580 was administered in diabetic rats induced by intraperitoneal injection of streptozotocin. The gastric emptying rate of rats was measured by using phenol red solution, and blood glucose levels and body weights were observed. p38 MAPK activity and iNOS expression were assessed by Western blot analysis. The expression of tumor necrosis factor (TNF)-\u03b1 and interleukin (IL)-1\u03b2 were determined by enzyme-linked immunosorbent assay.', 'Gastric emptying was delayed significantly in diabetic rats and improved significantly with SB203580; high glucose significantly activated p38 MAPK and increased the expression of iNOS, TNF-\u03b1 and IL-1\u03b2. The administration of SB203580 led to a significant decrease in the activation of p38 MAPK and the expression of iNOS, TNF-\u03b1 and IL-1\u03b2.",
            "output": [
                "Does blockade of p38 mitogen-activated protein kinase pathway ameliorate delayed gastric emptying in streptozotocin-induced diabetic rats?"
            ]
        },
        {
            "id": "task847-7870e95bc6284ec38891f26e084739d9",
            "input": "Matrix metalloproteinase-11 (MMP-11) is reported to be overexpressed in several cancers and may contribute to tumorigenesis. The current study investigated the association between the clinicopathological characteristics and plasma level of MMP-11 in oral squamous cell carcinoma (OSCC) patients.', 'The plasma MMP-11 concentration was determined by ELISA on 330 male OSCC patients. In addition, the metastatic effects of the MMP-11 knockdown on the oral cancer cells were investigated by cell migration assay. Our results showed that the plasma MMP-11 levels were significantly higher in patients with advanced T status (p\\u200a=\\u200a0.001), lymph node metastasis (p\\u200a=\\u200a0.006) and higher TNM stages (p<0.001). Moreover, treatment with the MMP-11 shRNA exerted an inhibitory effect on migration in SCC9 oral cancer cells.",
            "output": [
                "Is high level of plasma matrix metalloproteinase-11 associated with clinicopathological characteristics in patients with oral squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-38b7f0ab07d54b0bbf3ac6d7572db6d5",
            "input": "Interferon Lambda-3 (IFN-\u03bb3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-\u03bb3 genotype influences liver disease progression remains unclear.', 'We determined IFN-\u03bb3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992. Person-years follow-up was calculated for each individual from the date of enrolment to the development of first episode of decompensation, HCC, liver transplant, death or end of follow-up. The follow-up of patients who achieved SVR was censored at the time of IFN initiation. Kaplan-Meier curves and Cox regression analyses were used to assess the association between IFN-\u03bb3 genotype and clinical outcome.', 'IFN-\u03bb3 was determined in 264 patients (52% males, mean age 57\u00b18 years, 67% HCV genotype (G)1, while CC, CT and TT genotypes were 36%, 50% and 14%, respectively. During a median follow-up of 14.8 years, 149 (56%) patients received IFN. Overall, SVR was achieved in 31 (21%) patients, 40% among those with CC genotype (22% in G1 and 61% in G2, respectively) compared to 10% and 13% among patients with CT and TT genotypes (p<0.0001). Univariate and multivariate analyses found no association between IFN-\u03bb3 (CC vs. non-CC genotype) and disease progression.",
            "output": [
                "Is interferon lambda-3 associated with clinical outcome in patients with HCV-induced compensated cirrhosis : a long-term cohort study?"
            ]
        },
        {
            "id": "task847-5185da5e4cd54f1c83827210be0bcc31",
            "input": "Excessive anticipatory reactions to potential future adversity are observed across a range of anxiety disorders, but the neurogenetic mechanisms driving interindividual differences are largely unknown. We aimed to discover and validate a gene-brain-behavior pathway by linking presumed genetic risk for anxiety-related psychopathology, key neural activity involved in anxious anticipation, and resulting aversive emotional states.', \"The functional neuroanatomy of aversive anticipation was probed through functional magnetic resonance imaging in two independent samples of healthy subjects (n = 99 and n = 69), and we studied the influence of genetic variance in the serotonin transporter linked polymorphic region (5-HTTLPR). Skin conductance and startle data served as objective psychophysiological indices of the intensity of individuals' anticipatory responses to potential threat.\", 'Threat cues signaling risk of future electrical shock activated the dorsomedial prefrontal cortex (dmPFC), anterior insula, bed nucleus of the stria terminalis, thalamus, and midbrain consistently across both samples. Threat-related dmPFC activation was enhanced in 5-HTTLPR short allele carriers in sample 1 and this effect was validated in sample 2. Critically, we show that this region mediates the increase in anticipatory psychophysiological reactions in short allele carriers indexed by skin conductance (experiment 1) and startle reactions (experiment 2).",
            "output": [
                "Does dorsomedial Prefrontal Cortex mediate the Impact of Serotonin Transporter Linked Polymorphic Region Genotype on Anticipatory Threat Reactions?"
            ]
        },
        {
            "id": "task847-3074cc796d304c7fb0dc25eb6aa7e78d",
            "input": "To compare the efficacy of intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, and conventional radiotherapy for cervical cancer treatment.', 'Whole pelvis intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, and conventional radiotherapy plans were designed for 16 patients with stage IIB cervical cancer, each using the prescribed dose of 50.4 Gy/28 fractions. Dose-volume histograms of the target volume and organs at risk were evaluated.', 'Compared to the 3D conformal and conventional radiotherapy plans, the intensity-modulated radiotherapy plan demonstrated superior conformal treatment. The mean planning target volume dose of all three plans reached the target effective therapeutic dose. The planning target volume dose of the intensity-modulated radiotherapy plan was significantly higher than that of either the three-dimensional conformal radiotherapy or conventional radiotherapy plan (P<0.05). When more than 30 Gy was administered in intensity-modulated radiotherapy, organs at risk including the small intestine, rectum, bladder, and bone marrow received a significantly reduced volume of radiation. In comparison of the average planning target volume doses, significant volume reductions in irradiation of organs at risk were obtained with full bladders.",
            "output": [
                "Does intensity-modulated whole pelvic radiotherapy provide effective dosimetric outcomes for cervical cancer treatment with lower toxicities?"
            ]
        },
        {
            "id": "task847-f8a9cb15e4ee4b4abbbd3b385c6cc4a8",
            "input": "Patients infected with influenza A(H7N9) virus present with acute lung injury (ALI) that is due to severe pneumonia and systemic inflammation. It is often fatal because there are few effective treatment options. Complement activation has been implicated in the pathogenesis of virus-induced lung injury; therefore, we investigated the effect of targeted complement inhibition on ALI induced by H7N9 virus infection.', 'A novel neutralizing specific antihuman C5a antibody (IFX-1) was used. This antibody blocked the ability of C5a to induce granulocytes to express CD11b while not affecting the ability of C5b to form the membrane attack complex. African green monkeys were inoculated with H7N9 virus and treated intravenously with IFX-1.', 'The virus infection led to intense ALI and systemic inflammatory response syndrome (SIRS) in association with excessive complement activation. Anti-C5a treatment in H7N9-infected monkeys substantially attenuated ALI: It markedly reduced the lung histopathological injury and decreased the lung infiltration of macrophages and neutrophils. Moreover, the treatment decreased the intensity of SIRS; the body temperature changes were minimal and the plasma levels of inflammatory mediators were markedly reduced. The treatments also significantly decreased the virus titers in the infected lungs.",
            "output": [
                "Does treatment with anti-C5a antibody improve the outcome of H7N9 virus infection in African green monkeys?"
            ]
        },
        {
            "id": "task847-0fe9cd7c104846519050eba71f85798a",
            "input": "Vaccines are very important to reduce morbidity and mortality by preventable infectious diseases, especially during childhood. Optimal coverage is not always achieved, for several reasons. Here we assessed vaccine coverage for the first 12 months of age in children between 12 and 59 months old, residing in the urban area of a small Amazonian city, and factors associated with incomplete vaccination.', 'A census was performed in the urban area of Assis Brasil, in the Brazilian Amazon, in January 2010, with mothers of 282 children aged 12 to 59 months old, using structured interviews and data from vaccination cards. Mixed logistic regression was used to determine factors associated with incomplete vaccination schemes.', 'Only 82.6% of all children had a completed the basic vaccine scheme for the first year of life. Vaccine coverage ranged from 52.7% coverage (oral rotavirus vaccine) to 99.7% coverage (for Bacille Calmette-Gu\u00e9rin). The major deficiencies occurred in doses administered after the first six months of life. Incomplete vaccination was associated with not having enough income to buy a house (aOR = 2.12, 95% CI 1.06-4.21), low maternal schooling (aOR\\u2009= 2.60, 95% CI 1.28 - 5.29) , and time of residence of the child in the urban area of the city (aOR = 0.73, 95% CI 0.55 - 0.95).",
            "output": [
                "Are socioeconomic inequalities still a barrier to full child vaccine coverage in the Brazilian Amazon : a cross-sectional study in Assis Brasil , Acre , Brazil?"
            ]
        },
        {
            "id": "task847-415d4c303e6c4ad3add7dd61b90d1dc8",
            "input": "Mental fatigue can negatively impact on submaximal endurance exercise and has been attributed to changes in perceived exertion rather than changes in physiological variables. The impact of mental fatigue on maximal anaerobic performance is, however, unclear. Therefore, the aim of the present study was to induce a state of mental fatigue to examine the effects on performance, physiological and perceptual variables from subsequent tests of power, strength and anaerobic capacity.', 'Twelve participants took part in the single-blind, randomised, crossover design study. Mental fatigue was induced by 90 min of the computer-based Continuous Performance Task AX version. Control treatment consisted of 90 min of watching emotionally neutral documentaries. Participants consequently completed countermovement jump, isometric leg extension and a 3-min all-out cycling tests.', 'Results of repeated measures analysis of variance and paired t tests revealed no difference in any performance or physiological variable. Rating of perceived exertion tended to be greater when mentally fatigued (mental fatigue = 19 \u00b1 1 vs control = 18 \u00b1 1, p = 0.096, [Formula: see text] = .232) and intrinsic motivation reduced (mental fatigue = 11 \u00b1 4 vs control = 13 \u00b1 6, p = 0.063, d = 0.597) in the mental fatigue condition.",
            "output": [
                "Does mental fatigue affect maximal anaerobic exercise performance?"
            ]
        },
        {
            "id": "task847-f47094ad00704857879bc74cebc32853",
            "input": "The tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India.', 'We assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters.', 'Pro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg.",
            "output": [
                "Is tP53 Pro72 allele enriched in oral tongue cancer and frequently mutated in esophageal cancer in India?"
            ]
        },
        {
            "id": "task847-30b86809fa414b7992b5fa0c45003fc2",
            "input": "\u03b1-Enolase is a glycolytic enzyme with \"second jobs\" beyond its catalytic activity. However, its possible contribution to cardiac dysfunction remains to be determined. The present study aimed to investigate the role of \u03b1-enolase in doxorubicin (Dox)-induced cardiomyopathy as well as the underlying mechanisms.', 'The expression of \u03b1-enolase was detected in rat hearts and primary cultured rat cardiomyocytes with or without Dox administration. An adenovirus carrying short-hairpin interfering RNA targeting \u03b1-enolase was constructed and transduced specifically into the heart by intramyocardial injection. Heart function, cell apoptosis and mitochondrial function were measured following Dox administration. In addition, by using gain- and loss-of-function approaches to regulate \u03b1-enolase expression in primary cultured rat cardiomyocytes, we investigated the role of endogenous, wide type and catalytically inactive mutant \u03b1-enolase in cardiomyocyte apoptosis and ATP generation. Furthermore, the involvement of \u03b1-enolase in AMPK phosphorylation was also studied.', 'The mRNA and protein expression of cardiac \u03b1-enolase was significantly upregulated by Dox. Genetic silencing of \u03b1-enolase in rat hearts and cultured cardiomyocytes attenuated Dox-induced apoptosis and mitochondrial dysfunction. In contrast, overexpression of wide-type or catalytically inactive \u03b1-enolase in cardiomyocytes mimicked the detrimental role of Dox in inducing apoptosis and ATP reduction. AMPK dephosphorylation was further demonstrated to be involved in the proapoptotic and ATP-depriving effects of \u03b1-enolase.",
            "output": [
                "Does \u03b1-Enolase play a catalytically independent role in doxorubicin-induced cardiomyocyte apoptosis and mitochondrial dysfunction?"
            ]
        },
        {
            "id": "task847-1ec78c3a3c414294b507f17654e64886",
            "input": "Most burns happen in low- and middle-income countries. In India, deaths related to burns are more common in women than in men and occur against a complex background in which the cause - accidental or non-accidental, suicidal or homicidal - is often unclear. Our study aimed to understand the antecedents to burns and the problem of ascribing cause, the sequence of medicolegal events after a woman was admitted to hospital, and potential opportunities for improvement.', 'We conducted semi-structured interviews with 33 women admitted to two major burns units, their families, and 26 key informant doctors, nurses, and police officers. We used framework analysis to examine the context in which burns occurred and the sequence of medicolegal action after admission to hospital.', \"Interviewees described accidents, attempted suicide, and attempted homicide. Distinguishing between these was difficult because the underlying combination of poverty and cultural precedent was common to all and action was contingent on potentially conflicting narratives. Space constraint, problems with cooking equipment, and inflammable clothing increased the risk of accidental burns, but coexisted with household conflict, gender-based violence, and alcohol use. Most burns were initially ascribed to accidents. Clinicians adhered to medicolegal procedures, the police carried out their investigative requirements relatively rapidly, but both groups felt vulnerable in the face of the legal process. Women's understandable reticence to describe burns as non-accidental, the contested nature of statements, their perceived history of changeability, the limited quality and validity of forensic evidence, and the requirement for resilience on the part of clients underlay a general pessimism.",
            "output": [
                "Do a qualitative study of the background and in-hospital medicolegal response to female burn injuries in India?"
            ]
        },
        {
            "id": "task847-44328fa32eb04f07a09438fe8a6e0324",
            "input": "The purpose of the study was to determine whether racial differences exist in the pattern of local disease progression among men treated with radical prostatectomy (RP) for localized prostate cancer (PCa), which is currently unknown. In this study we evaluated the pattern of adverse pathologic features in an identical cohort of African-American (AA) and Caucasian (CS) men with PCa.', 'The overall cohort consisted of 1104 men (224 AA, and 880 CS) who underwent RP between 1990 and 2012. We compared preoperative factors and pathologic outcomes after RP across race groups. Multivariate analysis was used to identify factors predictive of adverse pathologic outcomes. The effect of race on adverse pathologic outcomes and biochemical control rate (BCR) was evaluated using multivariate regression model and Kaplan-Meier analysis.', 'The 10-year BCR was 59% versus 82% in AA and CS men, respectively (P = .003). There was no significant difference in extraprostatic spread (P = .14), positive surgical margin (P = .81), lymph node involvement (P = .71), or adverse pathologic features (P = .16) across race groups. However, among patients with \u2265 1 adverse pathologic features, AA men had higher rate of seminal vesicle invasion (SVI) compared with CS men (51% vs. 30%; P = .01). After adjusting for known predictors of adverse pathologic features AA race remained a predictor of SVI.",
            "output": [
                "Is african-american race a predictor of seminal vesicle invasion after radical prostatectomy?"
            ]
        },
        {
            "id": "task847-9f4c62d2dafb46afa3043bb51cdbfa54",
            "input": "Recently, a considerable amount of evidence suggested that anxiety, depression and other psychosocial variables might influence the outcomes of cardiac surgery. This study investigated the relationship between length of stay at the intensive care unit (ICU) and hospital after surgery and different psychosocial variables (e.g. depression, anxiety, self rated health, happiness, satisfaction).', 'We enrolled prospective patients who were waiting for elective cardiac surgery (N\\u2009=\\u2009267) and consented to take part in the study. We collected data of sociodemographic, medical and perioperative factors as well as psychosocial questionnaires completed 1.56\\xa0days (standard deviation [SD]\\u2009=\\u20090.7) before surgery. The primary clinical endpoint was an ICU stay of at least 3\\xa0days and the secondary was hospital stay of at least 10\\xa0days.', 'Two hundred sixty-seven patients participated in this study. Four patients (1.5%) died in the hospital and 38 patients (14.5%) spent more than 3\\xa0days in the ICU and 62 patients (23.2%) spent more than 10\\xa0days in the hospital. After controlling for medical and sociodemographic factors, lower self rated health (Adjusted Odds Ratio [AOR]: 0.51, 95% confidence interval [CI]: 0.28-0.95; p\\u2009=\\u20090.03), lower rate of happiness (AOR: 0.76, 95% CI: 0.59-0.97, p\\u2009=\\u20090.03), postoperative cardiac failure (AOR: 7.09, 95% CI:1.21-41.54; p\\u2009=\\u20090.03) and postoperative complications (AOR: 9.52, 95% CI: 3.76-24.11; p\\u2009<\\u20090.001) were associated with longer ICU stay. More than 10\\xa0days of hospital stay was associated with higher occurrence of COPD (AOR 4.56, CI: 1.95-10.67, p\\u2009<\\u20090.001), NYHA stage (AOR 6.76, CI: 2.57-17.79, p\\u2009<\\u20090.001), operation time (AOR 1.45, CI: 1.19-1.76, p\\u2009<\\u20090.001), female gender (AOR 2.16, CI: 1.06-4.40, p\\u2009=\\u20090.034) and lower self-rated health (AOR 0.63, CI: 0.41-0.99, p\\u2009=\\u20090.044).",
            "output": [
                "Is self-rated health associated with the length of stay at the intensive care unit and hospital following cardiac surgery?"
            ]
        },
        {
            "id": "task847-a2592850881d4873a74b282d47732b28",
            "input": "Sublethal doses of photon irradiation (IR) are suspected to increase tumor cell migration and support locoregional recurrence of disease, which has already been shown in other cell lines. This manuscript describes the effect of photon and carbon-ion IR on WHO class I meningioma cell migration and provides an approach to the underlying cellular mechanisms.', \"Meningioma cells were gained operatively at the university hospital in Homburg/Saar, Germany. For migration, membranes (8-\u00b5m pore sizes) were coated with collagen I, with collagen IV, and with fibronectin. Cells were analyzed in migration experiments with or without serum stimulation, with or without photon and carbon IR 24\\xa0h prior to experiments, and with or without integrin antibodies. Fluorescence-activated cell sorting (FACS) analyses of the integrins \u03b1\u03bd\u03b21, \u03b1\u03bd\u03b23, and \u03b1\u03bd\u03b25 were performed without IR and 6, 12 and 24\\xa0h after IR. Enzyme-linked immunosorbent assay (ELISA) analyses of matrix metalloproteinases (MMP)-2 and MMP-9 were realized with and without IR after cells were cultured on collagen I, collagen IV, or fibronectin for 24\\xa0h. Cells and supernatants for FACS and ELISA were stored at -\\u200918\\u2009\u00b0C. The significance level was set at 5\\u2009% using both Student's t test and two-way ANOVA.\", 'Migration of meningioma cells was serum-inducible (p\\u2009<\\u20090.001). It could be increased by photon IR (p\\u2009<\\u20090.02). The integrins \u03b1\u03bd\u03b21 and \u03b1\u03bd\u03b25 showed a 21 and 11\\u2009% higher expression after serum stimulation (not significant), respectively, and \u03b1\u03bd\u03b21 expression was raised by 14\\u2009% (p\\u2009=\\u20090.0057) after photon IR. Antibody blockage of the integrins \u03b1\u03bd\u03b21 and \u03b1\u03bd\u03b25 inhibited serum- and photon-induced migration. Expression of MMP-2 and MMP-9 remained unchanged after both IR and fetal bovine serum (FBS). Carbon-ion IR left both integrin expression and meningioma cell migration unaffected.",
            "output": [
                "Is integrin-based meningioma cell migration promoted by photon but not by carbon-ion irradiation?"
            ]
        },
        {
            "id": "task847-caa730fbaa4c420fbfaaa845c5400171",
            "input": "Early-life stress and a genetic predisposition to display an anxiety- and depressive-like phenotype are associated with behavioral and gastrointestinal (GI) dysfunction. Animals exposed to early-life stress, and those genetically predisposed to display anxiety or depressive behaviors, have proven useful tools in which to study stress-related GI disorders, such as irritable bowel syndrome (IBS). IBS is a heterogeneous disorder, and likely a consequence of both genetic and environmental factors. However, the combined effects of early-life stress and a genetic predisposition to display anxiety- and depression-like behaviors on GI function have not been investigated.', 'We assessed the effect of maternal separation (MS) on behavioral and GI responses in WKY animals relative to a normo-anxious reference strain.', 'Both non-separated (NS) WKY and WKY-MS animals displayed anxiety-like responses in the open-field test and depressive-like behaviors in the forced swim test relative to Sprague-Dawley rats. However, MS had no further influence on anxiety- and depressive-like behaviors exhibited by this stress-prone rat strain. Similarly, corticosterone levels measured after the OFT were insensitive to MS in WKY animals. However, WKY-MS displayed significantly increased colonic visceral hypersensitivity, fecal output, and altered colonic cholinergic sensitivity.",
            "output": [
                "Does early-life stress selectively affect gastrointestinal but not behavioral responses in a genetic model of brain-gut axis dysfunction?"
            ]
        },
        {
            "id": "task847-72b32642949b4848ae7c411d8480ca4a",
            "input": "Some studies done in Asian patients have shown that serum levels of hepatitis B virus (HBV) DNA predict the development of cirrhosis. However, it is unclear whether this also applies for non-Asian patients. This study investigated historic and current HBV DNA and quantitative hepatitis B surface antigen (HBsAg) levels as predictors of cirrhosis in non-Asian women with chronic HBV.', 'A retrospective cohort study of non-Asian women with chronic HBV was performed. Among other variables, HBV DNA and quantitative HBsAg levels were measured in stored historic serum samples obtained during pregnancy (period 1990-2004) and current serum samples (period 2011-2012) to determine any association with liver cirrhosis by liver stiffness measurement (LSM).', 'One hundred and nineteen asymptomatic, treatment-na\u00efve non-Asian women were included; the median number of years between the historic sample and the current sample was 17 (interquartile range (IQR) 13-20). The median historic log HBV DNA and quantitative log HBsAg levels were 2.5 (IQR 1.9-3.4) IU/ml and 4.2 (IQR 3.6-4.5) IU/ml, respectively. LSM diagnosed 14 patients (12%) with F3-F4 fibrosis, i.e. stiffness >8.1kPa. No association of cirrhosis was found with historic HBV DNA (relative risk (RR) 0.34, 95% confidence interval (CI) 0.05-2.44) or with the quantitative HBsAg level (HBsAg level >1000 IU/ml, RR 0.35, 95% CI 0.11-1.11). Multivariable analysis identified alcohol consumption (odds ratio (OR) 6.4, 95% CI 1.3-30.1), aspartate aminotransferase >0.5 times the upper limit of normal (OR 15.4, 95% CI 1.9-122.6), and prothrombin time (OR 12.0, 95% CI 1.2-120.4), but not HBV DNA or quantitative HBsAg level, to be independent predictors of the presence of cirrhosis.",
            "output": [
                "Are historic and current hepatitis B viral DNA and quantitative HBsAg level associated with cirrhosis in non-Asian women with chronic hepatitis B?"
            ]
        },
        {
            "id": "task847-fb6fb0acc21a46f787b0da8c096afab0",
            "input": "The members of the patatin-related phospholipase subfamily III (pPLAIIIs) have been implicated in the auxin response. However, it is not clear whether and how these genes affect plant and cell morphogenesis. Here, we studied the roles of the patatin-related phospholipase pPLAIII\u03b4 in auxin-responsive cell morphology and organ size in Arabidopsis and Brassica napus.', 'We show that overexpression of pPLAIII\u03b4 inhibited longitudinal growth but promoted transverse growth in most organs of Arabidopsis and Brassica napus. Compared to wild-type plants, pPLAIII\u03b4-KO plants exhibited enhanced cell elongation in hypocotyls, and pPLAIII\u03b4-OE plants displayed broadened radial cell growth of hypocotyl and reduced leaf pavement cell polarity. For the hypocotyl phenotype in pPLAIII\u03b4 mutants, which resembles the \"triple response\" to ethylene, we examined the expression of the ACS and ACO genes involved in ethylene biosynthesis and found that ACS4 and ACS5 were up-regulated by 2.5-fold on average in two OE lines compared with WT plants. The endogenous auxin distribution was disturbed in plants with altered pPLAIII\u03b4 expression. pPLAIII\u03b4-OE and KO plants exhibited different sensitivities to indole-3-acetic acid-promoted hypocotyl elongation in both light and dark conditions. Gene expression analysis of auxin-induced genes in the dark showed that OE plants maintained a higher auxin response compared with WT and KO plants after treatment with 1 \u03bcM IAA for 12 h. Following treatment with 10 \u03bcM IAA for 30 min in the light, early auxin-induced genes were significantly up-regulated in two OE plant lines.",
            "output": [
                "Does patatin-related phospholipase pPLAIII\u03b4 influence auxin-responsive cell morphology and organ size in Arabidopsis and Brassica napus?"
            ]
        },
        {
            "id": "task847-6e3ef9da1c444f2fa41049bedf87c97b",
            "input": "To examine the accuracy of HistoScanning (HS) in detecting seminal vesicle (SV) invasion (SVI) within prostate cancer (PCa) patients.', 'We relied on our prospective institutional database. Patients who received HS before radical prostatectomy were included in the study cohort. An experienced HS examiner retrospectively reanalyzed the HS data blinded to patient characteristics and pathologic results. The HS results for every single SV were compared with the corresponding findings from the final pathologic report after radical prostatectomy. An area under the receiver operating characteristic curve for the prediction of SVI by HS was calculated. Depending on HS signal volume cut-offs (>0, >0.2, and >0.5 mL), the sensitivity, specificity, positive predictive value, and negative predictive value for the prediction of SVI were assessed.', 'Overall, 131 patients and 262 SVs were assessable. Of those, 23 (17.5%) men had SVI, and 39 (14.9%) single SVs were infiltrated by tumor overall. The area under the receiver operating characteristic curve for predicting SVI by HS was 0.54. Depending on the HS signal volume cut-offs (>0, >0.2, and >0.5 mL), the sensitivity, specificity, positive predictive value, and negative predictive value for predicting SVI were 76.9%, 10.8%, 13.1%, and 72.7%; 61.5%, 24.2%, 12.4%, and 78.3%; and 46.2%, 50.2%, 14.0%, and 84.2%, respectively.",
            "output": [
                "Does histoscanning have low sensitivity and specificity for seminal vesicle invasion?"
            ]
        },
        {
            "id": "task847-61b913922af04c4f9f8434a2652e2c47",
            "input": "To investigate the effect of the percentage of free prostate-specific antigen (%fPSA) on future prostate cancer risk.', 'We examined serum total PSA (tPSA) and %fPSA annually in a prostate cancer-screening cohort between July 2001 and June 2011. Men with tPSA >4.0 ng/mL or tPSA of 2.0-4.0 ng/mL with %fPSA \u226412% were screened as positive and were recommended to undergo a biopsy. The study population consisted of 6368 men, aged 40-79 years, who had tPSA \u22644.0 ng/mL at initial screening and who subsequently underwent 1 or more screenings. We calculated the cumulative risk and hazard ratio of prostate cancer stratified by the initial %fPSA groups as quartiles of prostate cancer patients.', 'During a median follow-up of 36 months, 119 men were diagnosed with prostate cancer. The lowest quartile of %fPSA (<13.3%) was associated with a 21.2-fold higher risk of having prostate cancer compared with the highest quartile (>22.2%). For the subset with an initial tPSA \u22641.0 ng/mL, all men diagnosed with cancer had an initial %fPSA \u226433.3% (median). For the subset with tPSA >1.0 ng/mL, men with %fPSA \u226423.0% (median) had significantly higher risk for cancer than those with %fPSA >23.0% (P <.0001). Of the 114 men with prostate cancer in whom pathologic findings were available, 79 (69.3%) had a Gleason score \u22653 + 4 = 7.",
            "output": [
                "Is low percentage of free prostate-specific antigen ( PSA ) a strong predictor of later detection of prostate cancer among Japanese men with serum levels of total PSA of 4.0 ng/mL or less?"
            ]
        },
        {
            "id": "task847-d938ffd43b3445f194eaee40cf5ba945",
            "input": "Right ventricular pacing (RVP) has been associated with heart failure and increased mortality. His-bundle pacing (HBP) is more physiological but requires a mapping catheter or a backup right ventricular lead and is technically challenging.', 'We sought to assess the feasibility, safety, and clinical outcomes of permanent HBP in an unselected population as compared to RVP.', 'All patients requiring pacemaker implantation routinely underwent attempt at permanent HBP using the Select Secure (model 3830) pacing lead in the year 2011 delivered through a fixed-shaped catheter (C315 HIS) at one hospital and RVP at the second hospital. Patients were followed from implantation, 2 weeks, 2 months, 1 year, and 2 years. Fluoroscopy time (FT), pacing threshold (PTh), complications, heart failure hospitalization, and mortality were compared.', 'HBP was attempted in 94 consecutive patients, while 98 patients underwent RVP. HBP was successful in 75 patients (80%). FT was similar (12.7 \u00b1 8 minutes vs 10 \u00b1 14 minutes; median 9.1 vs 6.4 minutes; P = .14) and PTh was higher in the HBP group than in the RVP group (1.35 \u00b1 0.9 V vs 0.6 \u00b1 0.5 V at 0.5 ms; P < .001) and remained stable over a 2-year follow-up period. In patients with >40% ventricular pacing (>60% of patients), heart failure hospitalization was significantly reduced in the HBP group than in the RVP group (2% vs 15%; P = .02). There was no difference in mortality between the 2 groups (13% in the HBP group vs 18% in the RVP group; P = .45).",
            "output": [
                "Is permanent His-bundle pacing feasible , safe , and superior to right ventricular pacing in routine clinical practice?"
            ]
        },
        {
            "id": "task847-d809b36ffb2a47bea0afcea8684623e6",
            "input": "Implantable cardioverter-defibrillator (ICD) implantation is contraindicated in those with <1-year life expectancy.', 'The aim of this study was to develop a risk prediction score for 1-year mortality in patients with primary prevention ICDs and to determine the incremental improvement in discrimination when serum-based biomarkers are added to traditional clinical variables.', 'We analyzed data from the Prospective Observational Study of Implantable Cardioverter-Defibrillators, a large prospective observational study of patients undergoing primary prevention ICD implantation who were extensively phenotyped for clinical and serum-based biomarkers. We identified variables predicting 1-year mortality and synthesized them into a comprehensive risk scoring construct using backward selection.', 'Of 1189 patients deemed by their treating physicians as having a reasonable 1-year life expectancy, 62 (5.2%) patients died within 1 year of ICD implantation. The risk score, composed of 6 clinical factors (age \u226575 years, New York Heart Association class III/IV, atrial fibrillation, estimated glomerular filtration rate <30 mL/min/1.73 m(2), diabetes, and use of diuretics), had good discrimination (area under the curve 0.77) for 1-year mortality. Addition of 3 biomarkers (tumor necrosis factor \u03b1 receptor II, pro-brain natriuretic peptide, and cardiac troponin T) further improved model discrimination to 0.82. Patients with 0-1, 2-3, 4-6, or 7-9 risk factors had 1-year mortality rates of 0.8%, 2.7%, 16.1%, and 46.2%, respectively.",
            "output": [
                "Are clinical and serum-based markers associated with death within 1 year of de novo implant in primary prevention ICD recipients?"
            ]
        },
        {
            "id": "task847-4267ef44063c4a10abccec132451ff06",
            "input": "Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty liver disease, the most common chronic liver disease in the U.S. Fibrosis, a common feature of NASH, results from the dysregulation of fibrogenesis in hepatic stellate cells (HSCs). In this study, we investigated whether astaxanthin (ASTX), a xanthophyll carotenoid, can inhibit fibrogenic effects of transforming growth factor \u03b21 (TGF\u03b21), a key fibrogenic cytokine, in HSCs.', 'Reactive oxygen species (ROS) accumulation was measured in LX-2, an immortalized human HSC cell line. Quantitative realtime PCR, Western blot, immunocytochemical analysis, and in-cell Western blot were performed to determine mRNA and protein of fibrogenic genes, and the activation of Smad3 in TGF\u03b21-activated LX-2 cells and primary mouse HSCs.', 'In LX-2 cells, ROS accumulation induced by tert-butyl hydrogen peroxide and TGF\u03b21 was abolished by ASTX. ASTX significantly decreased TGF\u03b21-induced \u03b1-smooth muscle actin (\u03b1-SMA) and procollagen type 1, alpha 1 (Col1A1) mRNA as well as \u03b1-SMA protein levels. Knockdown of Smad3 showed the significant role of Smad3 in the expression of \u03b1-SMA and Col1A1, but not TGF\u03b21, in LX-2 cells. ASTX attenuated TGF\u03b21-induced Smad3 phosphorylation and nuclear translocation with a concomitant inhibition of Smad3, Smad7, TGF\u03b2 receptor I (T\u03b2RI), and T\u03b2RII expression. The inhibitory effect of ASTX on HSC activation was confirmed in primary mouse HSCs as evidenced by decreased mRNA and protein levels of \u03b1-SMA during activation.",
            "output": [
                "Does astaxanthin prevent TGF\u03b21-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells?"
            ]
        },
        {
            "id": "task847-69f0cf05d78c4853b01357557b375cb4",
            "input": "The purpose of this study was to determine the prevalence of vitamin D deficiency in CTCL patients and whether supplementation corrects vitamin D deficiency or treatment outcome.', 'Three hundred eleven CTCL patients including 27/311 (8.7%) with S\u00e9zary syndrome (SS), 169 cancer controls, and 69 normal controls from the M.D. Anderson clinics had 25(OH)D3 levels determined and categorized as deficient (< 20 ng/mL),insufficient (20-29 ng/mL), or sufficient (\u2265 30 ng/mL). Clinical response was determined according to a change in percent body surface area involvement.', \"Low 25(OH)D3 (< 30 ng/mL) levels were present in 76.9% of mycosis fungoides/SS patients, 75.2% of cancer controls, and 66.7% of healthy controls (P \u00bc .05, .07) and in 30% to 39% of historical normal controls. Correction of deficiency was successful in 35% or 55 of 156 patients who were given dealer's choice of either vitamin D2 at 50,000 IU orally (p.o.) biweekly or D3 1000 IU p.o. daily. Correction of vitamin D levels was noted in 27 of 100 (27%) patients given D3 and 28 of 56 (50%) given D2. Responses to standard CTCL therapy was similar among patients with corrected and persistently low levels (P \u00bc .51).",
            "output": [
                "Is vitamin D deficiency in mycosis fungoides and S\u00e9zary syndrome patients similar to other cancer patients?"
            ]
        },
        {
            "id": "task847-d1806737ea45466dae1108b08b69a861",
            "input": "Migraine is a common comorbidity among individuals with bipolar disorder, but the underlying mechanisms for this co-occurrence are poorly understood. The aim of this study was to investigate the genetic background of bipolar patients with and without migraine.', 'We performed a genome-wide association analysis contrasting 460 bipolar migraneurs with 914 bipolar patients without migraine from the Bipolar Genome Study (BiGS).', 'We identified one genome-wide significant association between migraine in bipolar disorder patients and rs1160720, an intronic single nucleotide polymorphism (SNP) in the NBEA gene (P=2.97 \u00d7 10(-8), OR: 1.82, 95% CI: 1.47-2.25), although this was not replicated in a smaller sample of 289 migraine cases.",
            "output": [
                "Does genome wide association study identify variants in NBEA associated with migraine in bipolar disorder?"
            ]
        },
        {
            "id": "task847-4c1de8f18ba84fbea9d37521dff94246",
            "input": "Nonalcoholic steatohepatitis (NASH) is associated with dyslipidemia and cardiovascular disease (CVD).', 'To determine the relationship between resolution of NASH and dyslipidemia.', 'Individuals in the Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial with paired liver biopsies and fasting lipid levels were included (N = 222). In the PIVENS trial individuals were randomised to pioglitazone 30 mg, vitamin E 800 IU or placebo for 96 weeks. Change in lipid levels at 96 weeks was compared between those with and without NASH resolution.', 'Dyslipidemia at baseline was frequent, with low high-density lipoprotein (HDL) (<40 mg/dL in men or <50 mg/dL in women) in 63%, hypertriglyceridaemia (\u2265150 mg/dL) in 46%, hypercholesterolaemia (\u2265200 mg/dL) in 47% and triglycerides (TG)/HDL >5.0 in 25%. Low-density lipoprotein (LD) \u2265160 mg/dL was found in 16% and elevated non-HDL cholesterol (non-HDL-C) (\u2265130 mg/dL) in 73%. HDL increased with NASH resolution but decreased in those without resolution (2.9 mg/dL vs. -2.5 mg/dL, P < 0.001). NASH resolution was associated with significant decreases in TG and TG/HDL ratio compared to those without resolution (TG: -21.1 vs. -2.3 mg/dL, P = 0.03 and TG/HDL: -0.7 vs. 0.1, P = 0.003). Non-HDL-C, LDL and cholesterol decreased over 96 weeks in both groups, but there was no significant difference between groups. Treatment group did not impact lipids.",
            "output": [
                "Is nASH resolution associated with improvements in HDL and triglyceride levels but not improvement in LDL or non-HDL-C levels?"
            ]
        },
        {
            "id": "task847-27ca1b569aed45ed976e0935c9916047",
            "input": "Cadherins are calcium-dependent cell-to-cell adhesion glycoproteins playing a critical role in the formation and maintenance of normal tissue architecture. In normal mammary gland, E-cadherin is expressed by luminal epithelial cells, while P-cadherin is restricted to myoepithelial cells. Changes in the expression of classical E- and P-cadherins have been observed in mammary lesions and related to mammary carcinogenesis. P-cadherin and E-cadherin expressions were studied in a series of feline normal mammary glands, hyperplastic/dysplastic lesions, benign and malignant tumours by immunohistochemistry and double-label immunofluorescence.', 'In normal tissue and in the majority of hyperplastic/dysplastic lesions and benign tumours, P-cadherin was restricted to myoepithelial cells, while 80% of the malignant tumours expressed P-cadherin in luminal epithelial cells. P-cadherin expression was significantly related to high histological grade of carcinomas (p <0.0001), tumour necrosis (p = 0.001), infiltrative growth (p = 0.0051), and presence of neoplastic emboli (p = 0.0401). Moreover, P-cadherin positive carcinomas had an eightfold likelihood of developing neoplastic emboli than negative tumours. Cadherins expression profile in high grade and in infiltrative tumours was similar, the majority expressing P-cadherin, regardless of E-cadherin expression status. The two cadherins were found to be co-expressed in carcinomas with aberrant P-cadherin expression and preserved E-cadherin.",
            "output": [
                "Is aberrant P-cadherin expression associated to aggressive feline mammary carcinomas?"
            ]
        },
        {
            "id": "task847-52a1d8dde13d4a5cbff64277d2da10f2",
            "input": "The fruits of Vitex rotundifolia L. are widely used to treat inflammation of the airway in Traditional Chinese medicine. Previous studies found that casticin, isolated from Vitex rotundifolia, could induce apoptosis of tumor cells. In this study, we evaluated the anti-inflammatory effects of casticin and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated macrophages.', 'RAW264.7 cells were pretreated with various concentrations of casticin (0.3-10\u03bcM), and then treated with LPS to induce inflammation. We assayed the levels of proinflammatory cytokines and prostaglandin E2 (PGE2) using ELISA, and examined the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and heme oxygenase (HO)-1 by Western blot. We also investigated the anti-inflammatory molecular mechanism by analyzing inflammatory-associated signaling pathways, including the nuclear transcription factor kappa-B (NF-\u03baB) and mitogen-activated protein kinase (MAPK) pathways.', 'We found casticin inhibited the levels of nitric oxide and PGE2, and decreased the production of proinflammatory cytokines such as interleukin (IL)-1\u03b2, IL-6, and tumor necrosis factor \u03b1 (TNF-\u03b1). In addition, iNOS and COX-2 expression levels were suppressed and casticin increased HO-1 and Nrf2 production in a concentration-dependent manner. Furthermore, casticin significantly inhibited NF-\u03baB subunit p65 proteins in the nucleus and decreased Akt and MAPK activation.",
            "output": [
                "Does casticin inhibit COX-2 and iNOS expression via suppression of NF-\u03baB and MAPK signaling in lipopolysaccharide-stimulated mouse macrophages?"
            ]
        },
        {
            "id": "task847-89c03a34b318419bbac3196b217b8057",
            "input": "The rubber tree, Hevea brasiliensis, is a major commercial source of natural rubber. Increasing the rubber yield of rubber trees is a very serious problem since the demands for high quality rubber materials are great. Establishment of a tapping system is based on an estimate of tapping intensity from the rubber tree. Latex flowing time is one of the most critical factors that determine the rubber yield. Long-term flow is a type of phenomenon of the rubber tree latex with longer flowing time than normal latex flow, and is always caused by intensive tapping. Thus, transcriptome and expression profiling data for long-term flowing latex (LFL) are needed as an important resource to identify genes and to better understand the biological mechanisms of latex flow in rubber trees.', 'The transcripts were sequenced using the Illumina sequencing platform. After cleaning, quality checks and sequencing, 98,697 transcripts and 38,584 unigenes were assembled with the mean size of 1437.31bp and 923.86bp, respectively. In BLAST searches of our database against public databases, 65.17% (25,147) of the unigenes were annotated with gene descriptions, conserved protein domains, or gene ontology terms. Functional categorization further revealed 853 individual unigenes related to long-term flow. According to KEGG classification, the clusters for \"cysteine and methionine metabolism\", \"energy\", \"oxidative phosphorylation\", \"terpenoid backbone biosynthesis\", \"plant hormone signal transduction\" and \"copper, potassium transporter\" were significantly enriched metabolic pathways.",
            "output": [
                "Do transcriptome sequencing and comparative analysis reveal long-term flowing mechanisms in Hevea brasiliensis latex?"
            ]
        },
        {
            "id": "task847-2a65b9ccdc344a2ca77365ef158b13e4",
            "input": "Growing evidence shows cannabidiol (CBD) modulates some of the effects of \u0394(9) -tetrahydrocannabinol (THC). CBD is a constituent of some strains of recreational cannabis but its content is highly variable. High CBD strains may have less memory-impairing effects than low-CBD strains and CBD can reverse behavioural effects of THC in monkeys. CBD/THC interactions in rodents are more complicated as CBD can attenuate or exacerbate the effects of THC. This study was undertaken to determine if CBD could reverse hypothermia or hypolocomotor effects caused by THC in rats.', 'Male Sprague-Dawley rats were prepared with radiotelemetry devices and then given doses of THC (10-30\\u2009mg\u00b7kg(-1) , i.p.) with or without CBD. Experiments determined the effect of simultaneous or 30\\u2009min pretreatment with CBD in a 1:1 ratio with THC, as well as the effect of CBD in a 3:1 ratio. Additional experiments determined the effects of pretreatment with the cannabinoid CB1 receptor antagonist SR141716 (rimonabant).', 'CBD did not attentuate THC-induced hypothermia or hypolocomotion but instead exaggerated these effects in some conditions. The antagonist SR141716 blocked hypolocomotor effects of THC for the first hour after injection and the hypothermia for 6\\u2009h; thus validating the pharmacological model.",
            "output": [
                "Does cannabidiol fail to reverse hypothermia or locomotor suppression induced by \u0394 ( 9 ) -tetrahydrocannabinol in Sprague-Dawley rats?"
            ]
        },
        {
            "id": "task847-835a1e9de3c246ad8112f70805c68a0b",
            "input": "The effective mechanisms of microRNAs (miRNAs) functions as oncogenes or tumour suppressors in human hepatocellular carcinoma (HCC) are still obscure. Here, we investigated the function and expression of miR-1228 in HCC.', 'The role of miR-1228 in HCC was determined by colony formation, transwell, and nude mice xenograft experiments. miR-1228 target gene were identified by EGFP reporter assays, real-time PCR, and western blot analysis. Dual-luciferase reporter assay and real-time PCR analysis are used to examine the regulation of p53.', \"miR-1228 promoted proliferation and metastasis, and facilitated the transition of cell cycle in hepatoma cells. miR-1228 downregulated p53 expression by binding to its 3'UTR. The ectopic expression of p53 abrogated the phenotypes induced by miR-1228. An inverse correlation existed between miR-1228 and p53 expression in hepatoma tissues compared with the adjacent tissues and three hepatoma cell lines. Moreover, we found that p53 suppressed the expression and promoter activity of miR-1228.",
            "output": [
                "Does miR-1228 promote the proliferation and metastasis of hepatoma cells through a p53 forward feedback loop?"
            ]
        },
        {
            "id": "task847-636679af4792492fa55cd0cea08e2bac",
            "input": "Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. Despite the advances in therapy over the years, its mortality remains high. The aim of this study was to evaluate the expression of small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression. We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.', 'A SENP1 small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells. VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR). Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.', 'VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues. Inhibition of SENP1 by siRNA was associated with decreased VEGF expression. SENP1 was over-expressed in 55 of the 100 NSCLC samples (55%) and was associated with a moderate and low histological tumor grade (3.6%, 38.2%, and 58.2% in high, moderate and low differentiated tumors, respectively, P = 0.046), higher T stage (10.9% in T1, and 89.1% in T2 and T3 tumor samples, P < 0.001) and TNM stage (10.9% in stage I, and 89.1% in stages II and III tumor samples, P < 0.001). The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group (76.4%) than that in the SENP1 low expression group (33.3%, P < 0.001). Sixty three patients received postoperative chemotherapy, including 34 with SENP1 over-expression and 29 with SENP1 low expression. Among the 34 patients with SENP1 over-expression, 22 (64.7%) patients developed recurrence or metastasis, significantly higher than those in the low expression group 27.6% (8/29) (P = 0.005). Multivariate Cox regression analysis showed that lymph node metastasis (P = 0.015), TNM stage (P = 0.001), and SENP1 expression level (P = 0.002) were independent prognostic factors for the survival of NSCLC patients.",
            "output": [
                "Does over-expression of small ubiquitin-like modifier proteases 1 predict chemo-sensitivity and poor survival in non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-f99a5f2a256148108dc9a68c4a2eafe4",
            "input": "We previously demonstrated that 6-benzylthioinosine (6-BT) could induce the differentiation of a subset of acute myeloid leukemia (AML) cell lines and primary AML cells regardless of their cytogenetics. In this study we investigated whether Wnt signaling pathways played roles in 6-BT-induced differentiation of AML cells.', \"We induced differentiation of HL-60 leukemic cells and primary AML cells in vitro using 6-BT. Real-time PCR (qPCR), western blot, and luciferase assays were used to examine the molecules' expression and biological activity in canonical and noncanonical Wnt signaling pathways. AML cell differentiation was measured by the Nitroblue tetrozolium (NBT) reduction assay.\", '6-BT regulated the expression of both canonical and non-canonical Wnt signaling molecules in HL-60 cells. Both 6-BT and all-trans-retinoic-acid (ATRA) reduced canonical Wnt signaling and activated noncanonical Wnt/Ca2+ signaling in HL-60 cells. Pre-treatment of HL-60 cells with an inhibitor of glycogen synthase kinase-3\u03b2 (GSK-3\u03b2), which activated canonical Wnt signaling, partly abolished the differentiation of HL-60 cells induced by 6-BT. Pre-treatment of HL-60 cells with an inhibitor of protein kinase C (PKC), resulting in inactivation of non-canonical Wnt/Ca2+ signaling, abolished 6-BT-induced differentiation of HL-60 cells. Several molecules in the non-canonical Wnt/Ca2+ pathway were detected in bone marrow samples from AML patients, and the expression of FZD4, FZD5, Wnt5a and RHOU were significantly reduced in newly diagnosed AML samples compared with normal controls.",
            "output": [
                "Is wnt signaling involved in 6-benzylthioinosine-induced AML cell differentiation?"
            ]
        },
        {
            "id": "task847-e655aabd465f485aa807c66fe7407fbd",
            "input": "Ginsenoside Rg3 is one of the active ingredients isolated from Panax ginseng\\u2005C.A. Meyer. Previous studies demonstrated that Rg3 has antioxidant and neuroprotective abilities.', 'The purpose of this study was to evaluate the protective effect of Rg3 on erectile function in streptozotocin (STZ)-induced diabetic rats.', 'Two-month-old Sprague-Dawley male rats received a one-time intraperitoneal (IP) STZ (60\\u2009mg/kg) or vehicle injection after a 16-hour fast. Three days later, rats were randomly divided into four groups and were treated with daily gavage feedings of a mix of distilled saline water and 0.5% carboxymethylcellulose or Rg3 dissolved in the mix at doses of 10\\u2009mg/kg and 100\\u2009mg/kg for 3 months. A sham group underwent IP injection of saline followed by daily gavage of the above mix for 3 months.', 'Erectile function was assessed by cavernosal nerve electrostimulation at 3 months. The penis was then harvested and deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed. Western blot was performed to examine cleaved caspase-3, platelet endothelial cell adhesion molecule (PECAM)-1, and smooth muscle actin (SMA). Neural regeneration was measured by nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by colorimetry.', 'In the negative control group, the functional evaluation showed a lower mean intracavernosal pressure (ICP) with cavernosal nerve stimulation than in the sham group; there was a significant change in the expression of cleaved caspase-3, bcl-2, bcl-xl, PECAM-1, and SMA, as well as in the SOD and MDA production in the corpus cavernosum. Histological analysis of specimens stained for NADPH showed a significant change in the staining quality of the neurons in the dorsal nerves; TUNEL showed a greater apoptotic index in corpus cavernosum cells. With daily oral gavage with 100\\u2009mg/kg Rg3, the ICP/mean arterial pressure value was significantly higher than in the controls. The level of cleaved caspase-3, bcl-2, bcl-xl, PECAM-1, and SMA and the number of positively stained nerve fibers tended to revert to normal after Rg3 treatment. The apoptotic index in corpus cavernosum cells was lowered.",
            "output": [
                "Does ginsenoside Rg3 improve erectile function in streptozotocin-induced diabetic rats?"
            ]
        },
        {
            "id": "task847-dd4056fd629e4ce2b09d32d7b9b137ca",
            "input": "Some cases with non-alcoholic fatty liver disease (NAFLD), particularly non-alcoholic steatohepatitis (NASH), can ultimately progress to liver cirrhosis. However, studies to clarify factors predictive of histological change in patients with NASH remain scarce. Our aim is to determine predictors of histological progression in Japanese patients with biopsy-proven NASH.', 'This retrospective cohort study enrolled 52 patients with NASH who underwent serial liver biopsies. Histological evaluation included NAFLD activity score (NAS) and liver fibrosis. The median interval between initial and second liver biopsies was 968\\u2009days. An alanine aminotransferase (ALT) response was defined as a decrease of 30% or more from baseline.', 'Of 52 patients, NAS was ameliorated in 30.8%, deteriorated in 30.8% and remained unchanged in 38.4%. Liver fibrosis was improved in 25.0% of patients, progressed in 25.0% and remained stable in 50.0%. Multivariate analysis identified ALT non-response as a predictor of deterioration of NAS (hazard ratio [HR], 5.85; P\\u2009=\\u20090.031) and progression of liver fibrosis (HR, 4.50; P\\u2009=\\u20090.029). The mean annual rate of fibrosis was 0.002 stages/year overall, increasing to 0.15 stages/year in ALT non-responders.",
            "output": [
                "Does serum alanine aminotransferase predict the histological course of non-alcoholic steatohepatitis in Japanese patients?"
            ]
        },
        {
            "id": "task847-f976028aad8f42c6affe615e3350c9ff",
            "input": "Notch signaling plays an acknowledged role in bile-duct development, but its involvement in cholangiocyte-fate determination remains incompletely understood. We investigated the effects of early Notch2 deletion in Notch2(fl/fl)/Alfp-Cre(tg/-) (\"Notch2-cKO\") and Notch2(fl/fl)/Alfp-Cre(-/-) (\"control\") mice. Fetal and neonatal Notch2-cKO livers were devoid of cytokeratin19 (CK19)-, Dolichos-biflorus agglutinin (DBA)-, and SOX9-positive ductal structures, demonstrating absence of prenatal cholangiocyte differentiation. Despite extensive cholestatic hepatocyte necrosis and growth retardation, mortality was only ~15%. Unexpectedly, a slow process of secondary cholangiocyte differentiation and bile-duct formation was initiated around weaning that histologically resembled the ductular reaction. Newly formed ducts varied from rare and non-connected, to multiple, disorganized tubular structures that connected to the extrahepatic bile ducts. Jaundice had disappeared in ~30% of Notch2-cKO mice by 6 months. The absence of NOTCH2 protein in postnatally differentiating cholangiocyte nuclei of Notch2-cKO mice showed that these cells had not originated from non-recombined precursor cells. Notch2 and Hnf6 mRNA levels were permanently decreased in Notch2-cKO livers. Perinatally, Foxa1, Foxa2, Hhex, Hnf1\u03b2, Cebp\u03b1 and Sox9 mRNA levels were all significantly lower in Notch2-cKO than control mice, but all except Foxa2 returned to normal or increased levels after weaning, coincident with the observed secondary bile-duct formation. Interestingly, Hhex and Sox9 mRNA levels remained elevated in icteric 6 months old Notch2-cKOs, but decreased to control levels in non-icteric Notch2-cKOs, implying a key role in secondary bile-duct formation.",
            "output": [
                "Does hepatic Notch2 deficiency lead to bile duct agenesis perinatally and secondary bile duct formation after weaning?"
            ]
        },
        {
            "id": "task847-c2800c5771be4f7782138271fa262dfc",
            "input": "By binding to T cell immunoglobulin mucin-3 (TIM-3) on activated Th1 cells, galectin-9 (Gal-9) negatively regulates Th1-type alloimmunity. Although T cells contribute to hepatic ischemia-reperfusion injury (IRI), it is unknown whether negative T cell-dependent TIM-3 co-stimulation may rescue IR-stressed orthotopic liver transplants from innate immunity-driven inflammation.', 'We used wild type (WT) and TIM-3 transgenic (Tg) mice (C57BL/6) as liver donors and recipients in a clinically-relevant model of hepatic cold storage (20 h at 4\u00b0C in UW solution) and syngeneic orthotopic liver transplantation (OLT).', \"Orthotopic liver transplants in WT or TIM-3Tg\u2192TIM-3Tg groups were resistant against IR-stress, evidenced by preserved hepatocellular function (serum ALT levels) and liver architecture (Suzuki's score). In contrast, orthotopic liver transplants in WT or TIM-3Tg\u2192WT groups were susceptible to IRI. TIM-3 induction in circulating CD4+ T cells of the recipient: (1) depressed T-bet/IFN-\u03b3, while amplifying GATA3 and IL-4/IL-10 expression in orthotopic liver transplants; (2) promoted T cell exhaustion (PD-1, LAG-3) phenotype; and (3) depressed neutrophil and macrophage infiltration/function in orthotopic liver transplants. In parallel studies, we documented for the first time that Gal-9, a natural TIM-3 ligand, was produced primarily by and released from IR-stressed hepatocytes, both in vivo and in vitro. Moreover, exogenous recombinant Gal-9 (rGal-9) potentiated liver resistance against IRI by depressing T cell activation and promoting apoptosis of CD4+ T cells.",
            "output": [
                "Does recipient T cell TIM-3 and hepatocyte galectin-9 signalling protect mouse liver transplants against ischemia-reperfusion injury?"
            ]
        },
        {
            "id": "task847-15f96f6077fb4043bad0514cb4d88ba5",
            "input": "Preoperative suspicion of malignancy in pancreatic neuroendocrine tumours (pNETs) is mostly based on tumour size. We retrospectively reviewed the contrast enhancement pattern (CEP) of a series of pNETs on multiphasic multidetector computed tomography (MDCT), to identify further imaging features predictive of lesion aggressiveness.', 'Sixty pNETs, diagnosed in 52 patients, were classified based on CEP as: type A showing early contrast enhancement and rapid wash-out; type B presenting even (B1) or only (B2) late enhancement. All tumours were resected allowing pathologic correlations.', 'Nineteen pNETs showed type A CEP (5-20 mm), 29 type B1 CEP (5-80 mm) and 12 type B2 (15-100 mm). All tumours were classified as well differentiated tumours, 19 were benign (WDt-b), 15 with uncertain behaviour (WDt-u) and 26 carcinomas (WDC). None of A lesions were malignant (12 WDt-b; 7 WDt-u), all B2 lesions were WDC, 7 B1 lesions were WDt-b, 8 WDt-u and 14 WDC; 4/34 (12 %) lesions \u22642cm were WDC. CEP showed correlation with all histological prognostic indicators.",
            "output": [
                "Does contrast enhancement pattern on multidetector CT predict malignancy in pancreatic endocrine tumours?"
            ]
        },
        {
            "id": "task847-97cbfd658aa940c2aef672a64b5097f3",
            "input": "Ketamine is a widely used anesthetic in obstetric and pediatric anesthesia. In the developing brain, the widespread neuron apoptosis triggered by ketamine has been demonstrated. However, little is known about its effect on neural stem cells (NSCs) function. This study aimed to investigate the effect of ketamine on proliferation of NSCs from neonatal rat hippocampus.', \"Neural stem cells were isolated from the hippocampus of Sprague-Dawley rats on postnatal day 3. In dose-response experiments, cultured neural stem cells (NSCs) were exposed to different concentrations of ketamine (0-1000 \u00b5M) for 24 hrs. The proliferative activity of NSCs was evaluated by 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay. Apoptosis of neural stem cells were assessed using caspase-3 by western blot. The intracellular Ca(2+) concentration ([Ca(2+)]i) in NSCs was analyzed by flow cytometry. The activation of protein kinase C-\u03b1 (PKC\u03b1) and the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) were measured by western blot analysis.\", 'Clinical relevant concentration of ketamine (10, 20 and 50 \u00b5M) did not markedly alter the proliferation of NSCs from neonatal rat hippocampus in vitro. However, ketamine (200, 500, 800 and 1000\u03bcM) significantly inhibited the proliferation of NSCs and did not affect the expression of caspase-3. Meanwhile, ketamine (200, 500, 800 and 1000\u03bcM) also markedly decreased [Ca(2+)]i as well as suppressed PKC\u03b1 activation and ERK1/2 phosphorylation in NSCs. A combination of subthreshold concentrations of ketamine (100 \u03bcM) and Ca(2+) channel blocker verapamil (2.5 \u03bcM), PKC\u03b1 inhibitor chelerythrine (2.5 \u03bcM) or ERK1/2 kinase inhibitor PD98059 (5 \u03bcM) significantly produced suprathreshold effects on PKC\u03b1 activation, ERK1/2 phosphorylation and NSC proliferation.",
            "output": [
                "Does ketamine inhibit proliferation of neural stem cell from neonatal rat hippocampus in vitro?"
            ]
        },
        {
            "id": "task847-8cddb6b7dd8e4205828d68a216356924",
            "input": "Wheat (Triticum aestivum L.) is an economically important grain crop. Two-dimensional gel-based approaches are limited by the low identification rate of proteins and lack of accurate protein quantitation. The recently developed isobaric tag for relative and absolute quantitation (iTRAQ) method allows sensitive and accurate protein quantification. Here, we performed the first iTRAQ-based quantitative proteome and phosphorylated proteins analyses during wheat grain development.', 'The proteome profiles and phosphoprotein characterization of the metabolic proteins during grain development of the elite Chinese bread wheat cultivar Yanyou 361 were studied using the iTRAQ-based quantitative proteome approach, TiO2 microcolumns, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among 1,146 non-redundant proteins identified, 421 showed at least 2-fold differences in abundance, and they were identified as differentially expressed proteins (DEPs), including 256 upregulated and 165 downregulated proteins. Of the 421 DEPs, six protein expression patterns were identified, most of which were up, down, and up-down expression patterns. The 421 DEPs were classified into nine functional categories mainly involved in different metabolic processes and located in the membrane and cytoplasm. Hierarchical clustering analysis indicated that the DEPs involved in starch biosynthesis, storage proteins, and defense/stress-related proteins significantly accumulated at the late grain development stages, while those related to protein synthesis/assembly/degradation and photosynthesis showed an opposite expression model during grain development. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 12 representative genes encoding different metabolic proteins showed certain transcriptional and translational expression differences during grain development. Phosphorylated proteins analyses demonstrated that 23 DEPs such as AGPase, sucrose synthase, Hsp90, and serpins were phosphorylated in the developing grains and were mainly involved in starch biosynthesis and stress/defense.",
            "output": [
                "Does iTRAQ-based quantitative proteome and phosphoprotein characterization reveal the central metabolism changes involved in wheat grain development?"
            ]
        },
        {
            "id": "task847-61a8db5074024079af2b99f7a47d45f5",
            "input": "Low vitamin D status (serum 25(OH)D concentration) is associated with increased incidence and unfavourable outcome of various types of cancer. However, there are limited data on influence of serum 25(OH)D on risk and prognosis of malignant melanoma.', 'Basal serum 25(OH)D concentrations were retrospectively analyzed in a cohort of melanoma patients (n\\u200a=\\u200a324) and healthy controls (n\\u200a=\\u200a141). We tested the hypothesis that serum 25(OH)D concentrations are predictive of melanoma risk, thickness of primary melanomas, and overall survival (OS).', 'Median serum 25(OH)D concentrations were significantly lower (p\\u200a=\\u200a0.004) in melanoma patients (median\\u200a=\\u200a13.6 ng/ml) as compared to controls (median\\u200a=\\u200a15.6 ng/ml). Primary tumors of patients with low serum 25(OH)D concentrations (<10 ng/ml) had significantly (p\\u200a=\\u200a0.006) greater Breslow thickness (median: 1.9 mm) as compared to patients with higher levels (>20 ng/ml; median: 1.00 mm). Patients with 25(OH)D serum concentrations in the lowest quartile had inferior overall survival (median: 80 months) comparing with the highest quartile (median: 195 months; p\\u200a=\\u200a0.049).",
            "output": [
                "Are low serum 25-hydroxyvitamin d concentrations associated with increased risk for melanoma and unfavourable prognosis?"
            ]
        },
        {
            "id": "task847-dde320cca4af457ea436d4613a5190c5",
            "input": "Rural primary health centers frequently treat patients with tick bites. This study compares everyday clinical practice at our primary healthcare center to practices recommended by current scientific evidence.', 'To describe the everyday management of tick bites by different healthcare professionals and to compare this management to evidence-based therapy guidelines.', 'Cross-sectional, descriptive observational study.', 'Data was collected through an anonymous self-completed questionnaire. The form was filled out by a consecutive sample of nurses, physicians and pediatricians of the clinical management unit of Medina-Sidonia (C\u00e1diz).', 'Most nurses in the sample group use some type of product to facilitate the extraction of the tick (10 of the 11 surveyed nurses, 90.9%). The most frequently used products were chloroethyl and local anesthetic. In addition, nine nurses use gentle traction with tweezers (81.82%) to remove the tick. In the physician sample group, 3 out of 12 respondents (25%) prescribe antibiotics in all cases and nine stated that they knew which antibiotic should be used as first choice. In both cases, a high number of healthcare providers confirm giving post-extraction advice to patients: 11 in the medical community (91.66%) and nine nurses (81.82%).",
            "output": [
                "Does [ Descriptive study of healthcare professionals ' management of tick bite ]?"
            ]
        },
        {
            "id": "task847-5f7c2ea72fa8413bbdd593cdfb12e07a",
            "input": "Cardiac troponin is widely accepted as a biomarker of myocyte injury in patients with myocardial ischemia. Patients with congestive heart failure are also associated with elevated cardiac troponin and it is a very sensitive prognostic marker. However, the mechanisms of troponin elevation in patients with heart failure are not fully understood. Decompensated state itself is suggested as a factor contributing to elevated cardiac troponin-T. However comparison between invasive hemodynamic parameters and cardiac troponin-T is insufficient.', 'Data were collected from 167 patients in stable, chronic HF, without acute coronary syndrome, recent revascularization, mitral stenoses, hemodialysis, or clinically significant right HF. We evaluated the correlations and 95% confidence intervals (CI) between invasive hemodynamic measurements and serum high-sensitivity (hs) concentrations of cTnT.', 'The serum cTnT concentration was equal to or more than the detection threshold (0.003ng/ml) in all patients. The serum cTnT concentration was equal to or more than the cut-off value of 0.014ng/ml in 46% of patients. By multiple variable analysis, left ventricular (LV) end-diastolic pressure (EDP; adjusted coefficient=0.014; 95% CI 0.0003-0.029; P=0.046) was positively correlated, while hemoglobin (adjusted coefficient=-0.079; 95% CI -0.140 to -0.018; P=0.012), estimated glomerular filtration rate (adjusted coefficient=-0.008; 95% CI -0.013 to -0.003; P=0.004), and LV ejection fraction (EF; adjusted coefficient=-0.011; 95% CI -0.018 to -0.003; P=0.004) were negatively correlated with hs-cTnT concentrations.",
            "output": [
                "Do left ventricular end-diastolic pressure and ejection fraction correlate independently with high-sensitivity cardiac troponin-T concentrations in stable heart failure?"
            ]
        },
        {
            "id": "task847-a7e174721e7540ab98262f6b679eaa35",
            "input": "The goals of this study were to evaluate the complication rate for intraoperative placement of a long-term central venous catheter (CVC) using intraoperative ultrasound (US) and fluoroscopy and to examine the feasibility for eliminating routine postprocedure chest X-ray.', 'Retrospective data pertaining to operative insertion of long-term CVC were collected and the rate of procedural complications was determined.', 'From January 2008 to August 2013, 351 CVCs were placed via the internal jugular vein using US. Of these, 93% had a single, successful internal jugular vein insertion. The complications included 4 arterial sticks (1.14%). Starting in October 2012, postprocedure chest radiography (CXR) was eliminated in 170 cases, with no complications. A total of $29,750 in charges were deferred by CXR elimination.",
            "output": [
                "Does image-guided placement of long-term central venous catheters reduce complications and cost?"
            ]
        },
        {
            "id": "task847-ccb98f61746e41e883de24293e2f7dd0",
            "input": "Exosomes are 30-100 nm membrane vesicles of endocytic origin, mediating diverse biological functions including tumor cell invasion, cell-cell communication and antigen presentation through transfer of proteins, mRNAs and microRNAs. Recent evidence suggests that microRNAs can be released through ceramide-dependent secretory machinery regulated by neutral sphingomyelinase 2 (nSMase2) enzyme encoded by the smpd3 gene that triggers exosome secretion. However, whether exosome-mediated microRNA transfer plays any role in cell invasion remains poorly understood. Thus, the aim of this study was to identify the exosomal microRNAs involved in breast cancer invasion.', 'The expression level of endogenous and exosomal miRNAs were examined by real time PCR and the expression level of target proteins were detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study its uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-10b was estimated by invasion assay.', 'In this study, we demonstrate that microRNA carrying exosomes can be transferred among different cell lines through direct uptake. miR-10b is highly expressed in metastatic breast cancer MDA-MB-231 cells as compared to non-metastatic breast cancer cells or non-malignant breast cells; it is actively secreted into medium via exosomes. In particular, nSMase2 or ceramide promotes the exosome-mediated miR-10b secretion whereas ceramide inhibitor suppresses this secretion. Moreover, upon uptake, miR-10b can suppress the protein level of its target genes such as HOXD10 and KLF4, indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could induce the invasion ability of non-malignant HMLE cells.",
            "output": [
                "Does exosome-mediated transfer of miR-10b promote cell invasion in breast cancer?"
            ]
        },
        {
            "id": "task847-0eb90adda37d4b259420ead50989ea87",
            "input": "To investigate clinical outcomes of coronary intervention using a biolimus-eluting stent (BES) compared with a sirolimus-eluting stent (SES) in patients with acute myocardial infarction (AMI) in the Limus Eluted from A Durable versus ERodable Stent (LEADERS) coating trial at the final 5-year follow-up.', 'The LEADERS trial is a multicentre all-comer study, where patients (n=1707) were randomised to percutaneous intervention with either BES containing biodegradable polymer or SES containing durable polymer. Out of 1707 patients enrolled in this trial, 573 patients had percutaneous coronary intervention for AMI (BES=280, SES=293) and were included in the current analysis. Patient-oriented composite endpoint (POCE, including all death, all myocardial infarction (MI) and all revascularisations), major adverse cardiac events (MACE, including cardiac death, MI and clinically indicated target vessel revascularisation) and stent thrombosis were assessed at 5-year follow-up.', 'The baseline clinical, angiographic and procedural characteristics were well matched between BES and SES groups. In all patients with AMI, coronary intervention with a BES, compared with SES, significantly reduced POCE (28.9% vs 42.3%; relative risk (RR) 0.61, 95% CI 0.47 to 0.82, p=0.001) at 5-year follow-up. There was also a reduction in MACE rate in the BES group (18.2% vs 25.9%; RR 0.67, 95% CI 0.47 to 0.95, p=0.025); however, there was no difference in cardiac death and stent thrombosis. In patients with ST-elevation MI (STEMI), coronary intervention with BES significantly reduced POCE (24.4% vs 39.3%; RR 0.55, 95% CI 0.36 to 0.85, p=0.006), MACE (12.6% vs 25.0%; RR 0.47, 95% CI 0.26 to 0.83, p=0.008) and cardiac death (3.0% vs 11.4%; RR 0.25, 95% CI 0.08 to 0.75, p=0.007), along with a trend towards reduction in definite stent thrombosis (3.7% vs 8.6%; RR 0.41, 95% CI 0.15 to 1.18, p=0.088), compared with SES.",
            "output": [
                "Does biolimus-eluting stent with biodegradable polymer improve clinical outcomes in patients with acute myocardial infarction?"
            ]
        },
        {
            "id": "task847-bfe85d11909e4a5a9e308ce3f8856d9d",
            "input": "We have reported that triptolide can inhibit airway remodeling in a murine model of asthma via TGF-\u03b21/Smad signaling. In the present study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism.', 'Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentration of triptolide before stimulated by TGF-\u03b21. Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Signal proteins (Smad2, Smad3 and Smad7) were detected by western blotting analysis.', 'Triptolide significantly inhibited TGF-\u03b21-induced ASMC proliferation (P<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. No pro-apoptotic effects were detected under the concentration of triptolide we used. Western blotting analysis showed TGF-\u03b21 induced Smad2 and Smad3 phosphorylation was inhibited by triptolide pretreatment, and the level of Smad7 was increased by triptolide pretreatment.",
            "output": [
                "Does triptolide inhibit TGF-\u03b21-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling?"
            ]
        },
        {
            "id": "task847-8d5978dc7ac146d59a828d851c92c6a0",
            "input": "What are typical values of physical function for women diagnosed with breast cancer and how do these compare to normative data?', 'Systematic review with meta-analysis.', 'Women diagnosed with breast cancer who were before, during or after treatment.', 'Physical function was divided into three categories: aerobic capacity, upper and lower extremity muscular fitness, and mobility. Measures of aerobic capacity included field tests (6-minute walk test, 12-minute walk tests, Rockport 1-mile test, and 2-km walk time) and submaximal/maximal exercise tests on a treadmill or cycle ergometer. Measures of upper and lower extremity muscular fitness included grip strength, one repetition maximum (bench, chest or leg press), muscle endurance tests, and chair stands. The only measure of mobility was the Timed Up and Go test.', 'Of the 1978 studies identified, 85 were eligible for inclusion. Wide ranges of values were reported, reflecting the range of ages, disease severity, treatment type and time since treatment of participants. Aerobic fitness values were generally below average, although 6-minute walk time was closer to population norms. Upper and lower extremity strength was lower than population norms for women who were currently receiving cancer treatment. Lower extremity strength was above population norms for women who had completed treatment.",
            "output": [
                "Are aerobic capacity and upper limb strength reduced in women diagnosed with breast cancer : a systematic review?"
            ]
        },
        {
            "id": "task847-8e34703af74542fbbfdd9aa70a78548d",
            "input": "To compare rates of pelvic inflammatory disease (PID) among women who did and did not receive an intrauterine device (IUD) the day they sought emergency contraception (EC) or pregnancy testing.', 'Women, 15 to 45\\xa0years of age, who sought EC or pregnancy testing from an urban family planning clinic completed surveys at the time of their clinic visit (August 22, 2011, to May 30, 2013) and 3 months after their clinic visit. The surveys assessed contraceptive use and symptoms, testing, and treatment for sexually transmitted infections (STI) and PID. We reviewed the medical records of participants who reported IUD placement within 3\\xa0months of enrollment and abstracted de-identified electronic medical record (EMR) data on all women who sought EC or pregnancy testing from the study clinic during the study period.', 'During the study period, 1,060 women visited the study clinic; 272 completed both enrollment and follow-up surveys. Among survey completers with same-day IUD placement, PID in the 3\\xa0months after enrollment was not more common (1/28 [3.6%]; 95% CI, 0%-10.4%) than among women who did not have a same-day IUD placed (11/225 [4.9%]; 95% CI, 2.7%-8.6%; p\\xa0=\\xa0.71). Chart review and EMR data similarly showed that rates of PID within 3\\xa0months of seeking EC or pregnancy testing were low whether women opted for same-day or delayed IUD placement.",
            "output": [
                "Is same-day intrauterine device placement rarely complicated by pelvic infection?"
            ]
        },
        {
            "id": "task847-77cc651935e14a5d9677cc25ad8aff94",
            "input": "Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and \u03b2-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT).', 'We studied 372 FDR-T2DM subjects (ages,18-65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob-) or obese (Ob+)] and TGs levels (TG-, <150\\u2009mg/dL, or TG+, \u2265150\\u2009mg/dL). \u03b2-cell function, IR, and IS were determined by the homeostasis model assessment of \u03b2-cell function (HOMA2-\u03b2), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively.', 'The obese subjects with elevated TGs levels had 21%-60% increased \u03b2-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with \u03b2-cell function (\u03c1=0.502, P<0.001).",
            "output": [
                "Do obese first-degree relatives of patients with type 2 diabetes with elevated triglyceride levels exhibit increased \u03b2-cell function?"
            ]
        },
        {
            "id": "task847-42de5bc81f6e48ff857c9b934f896fde",
            "input": "Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) as important human pathogens are causes of nosocomial infections worldwide. Burn patients are at a higher risk of local and systemic infections with these microorganisms.', 'A screening method for MRSA by using a multiplex polymerase chain reaction (PCR) targeting the 16S ribosomal RNA (rRNA), mecA, and nuc genes was developed. The aim of the present study was to investigate the potential of this PCR assay for the detection of MRSA strains in samples from burn patients.', 'During an 11-month period, 230 isolates (53.11%) of Staphylococcus spp. were collected from burn patients. The isolates were identified as S. aureus by using standard culture and biochemical tests. DNA was extracted from bacterial colonies and multiplex PCR was used to detect MRSA and MRCoNS strains.', 'Of the staphylococci isolates, 149 (64.9%) were identified as S. aureus and 81 (35.21%) were described as CoNS. Among the latter, 51 (62.97%) were reported to be MRCoNS. From the total S. aureus isolates, 132 (88.6%) were detected as MRSA and 17 (11.4%) were methicillin-susceptible S. aureus (MSSA). The presence of the mecA gene in all isolates was confirmed by using multiplex PCR as a gold standard method.",
            "output": [
                "Do identification of methicillin-resistant Staphylococcus aureus ( MRSA ) strains isolated from burn patients by multiplex PCR?"
            ]
        },
        {
            "id": "task847-b1a0e70f88de4c0598869f14ee2bfdeb",
            "input": "IQ-domain GTPase-activating protein 1 (IQGAP1) binds to Dishevelled (Dvl) and functions as a modulator of Dvl nuclear localization in Xenopus embryos. However, the relationship between IQGAP1 and Dvl in tumor tissues is unclear.', 'We used immunohistochemistry to assess the expressions of IQGAP1 and Dvl in a cohort of 111 non-small cell lung cancer (NSCLC) patients. Association of their localization expressions with clinicopathological factors was also analyzed.', 'The positive rate of IQGAP1 in primary tumors was 48.6% (54/111) for its cytoplamic expression, 9.0% (10/111) for nuclear expression and 31.5% (35/111) for membranous expression; the positive rate of Dvl was 65.8% (73/111) for cytoplamic expression, 9.9% (11/111) for nuclear expression and 10.8% (12/111) for membranous expression. Coexpression rate of IQGAP1 and Dvl was 77.8% (42/54) in the cytoplasm, 80.0% (8/10) in the nucleus and 8.6% (3/35) in the membrane. Coexpression of IQGAP1 and Dvl in the cytoplasm and nucleus were significantly correlated (P<0.05), but not in the membrane (P>0.05). The positive expression rates of cyclin D1 and c-myc were significantly higher in the group of IQGAP1 and Dvl coexpression in the nucleus than that in the cytoplasm. Coexpression rate of IQGAP1 and Dvl in the cytoplasm and nucleus was significantly higher in lymph nodal metastases (63.3%, 19/30) than in primary growths (38.3%, 31/81), correlating with poor prognosis. Five-year survival time after resection in the group with their coexpression in the cytoplasm and nucleus was significantly lower than that with no coexpression (44.705\u00b13.355 vs 58.403\u00b12.543 months, p<0.05).",
            "output": [
                "Is coexpression of IQ-domain GTPase-activating protein 1 ( IQGAP1 ) and Dishevelled ( Dvl ) correlated with poor prognosis in non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-817028ed5d2b4e7982fc7f19a971a939",
            "input": "In Cameroon, most women use traditional medicine for the treatment of pregnancy and childbirth complaints. In order to identify some of the medicinal plants locally used to alleviate these complaints, an ethnobotanical survey was undertaken in five villages of Menoua Division (West-Cameroon).', 'Interviews were conducted through structured questionnaires among 24 traditional healers and 179 women living either in the town of Dschang or in 4 neighboring villages. After having recorded the interviewee personal information on issues related to medicinal plants utilization, a literature investigation on their therapeutic or pharmacological effects and phytochemical composition was conducted.', 'A total of 88 medicinal plants species used to treat 24 conditions occurring during or after pregnancy and belonging to 70 genera or 34 families were recorded. Maximum medicinal uses of plants are reported for the treatment of the following ailments: swelling of legs and ankles (23%), facilitation of delivery (22%), cleaning of the baby (12%). Most herbal remedies are prepared with the leaves (30%), leaves+stems (28%) and whole plant (23%) as maceration (76%). The majority of women who used medicinal plants were very satisfied (75 %) and it is reported that most of these plants are used in the treatment of women health conditions.",
            "output": [
                "Do ethnobotanical survey of medicinal plants used for pregnant women\u05f3s health conditions in Menoua division-West Cameroon?"
            ]
        },
        {
            "id": "task847-f7a6c959b19b4d55aa51971dab778af7",
            "input": "Shexiang Tongxin dropping pill (STDP) is a formulation of Traditional Chinese Medicine mainly used for clinical treatment of stable angina pectoris in China.', 'To investigate the effects and mechanisms of STDP treatment on atherosclerosis.', \"ApoE deficient (ApoE(-/-)) mice were utilized to evaluate the effect of STDP treatment (30 mg/kg/day) on atherosclerotic lesions. Histopathological features of atherosclerotic lesions, serum levels of lipid proteins, parameters of oxidative stress and pro-inflammatory cytokines were measured by H&E staining, Masson's trichrome staining and ELISA, respectively. Real-time PCR analyses were performed to examine the aortic expression of atherosclerosis-associated microRNAs.\", 'The STDP treatment resulted in attenuated atherosclerotic lesion manifested by reduced lipid deposition, fibrosis and oxidative stress. It also led to increase in serum levels of GSH and SOD, decrease in MDA, decrease in CHO, TG, LDL, ox-LDL and increase in HDL, respectively. Additionally, the levels of pro-inflammatory cytokines including IL-2, IL-6, TNF-\u03b1 and \u03b3-IFN were markedly reduced by STDP treatment. Furthermore, STDP treatment was associated with a significant reduction in the aortic expression of miR-21a, miR-132, miR-126a, miR-155 and increased expression of miR-20a.",
            "output": [
                "Does shexiang Tongxin dropping pill attenuate atherosclerotic lesions in ApoE deficient mouse model?"
            ]
        },
        {
            "id": "task847-76debf3a4ed34790bde595c35268eae1",
            "input": "\u03b1-Actinins are myofibril anchor proteins that influence the contractile properties of skeletal muscles. ACTN2 is expressed in slow type I and fast type II fibers, whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (ie, changing 577RR to 577XX, the R577X polymorphism) results in the absence of \u03b1-actinin-3 in about 18% of Europeans, diminishes fast contractile ability, enhances endurance performance, and reduces bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in the masseter muscle of orthognathic surgery patients to determine the genotype associations with malocclusion.', 'Clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 single nucleotide polymorphisms, real-time polymerase chain reaction quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype.', 'Muscle mRNA expression level was significantly different for ACTN3 single nucleotide polymorphism genotypes (P\\xa0<0.01). The frequency of ACTN3 genotypes was significantly different for the sagittal and vertical classifications of malocclusion, with the clearest association being elevated 577XX genotype in skeletal Class II malocclusion (P\\xa0=\\xa00.003). This genotype also resulted in significantly smaller diameters of fast type II fibers in masseter muscles (P\\xa0=\\xa00.002).",
            "output": [
                "Do aCTN3 R577X genotypes associate with Class II and deepbite malocclusions?"
            ]
        },
        {
            "id": "task847-0db6b5841e6048689a40f8bf71f7ff8e",
            "input": "We sought to determine whether outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) vary according to CTO target vessel: left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA).', 'We evaluated the clinical and angiographic characteristics and procedural outcomes of 636 patients who underwent CTO PCI at 6 high-volume centres in the United States between January 2012 and March 2014.', 'The CTO target vessel was the RCA in 387 cases (61%), LAD in 132 (21%), and LCX in 117 (18%). LCX lesions were more tortuous and RCA lesions had greater occlusion length and Japanese Chronic Total Occlusion (J-CTO) score, but were less likely to have a side branch at the proximal cap and had more developed collateral circulation. The rate of procedural success was lower in LCX CTOs (84.6%), followed by RCA (91.7%), and LAD (94.7%) CTOs (P = 0.016). Major complications tended to occur more frequently in LCX PCI (4.3% vs 1.0% for RCA vs 2.3% for LAD; P = 0.07). LCX and RCA CTO PCI required longer fluoroscopy times (45 [interquartile range (IQR), 30-74] minutes vs 45 [IQR, 21-69] minutes for RCA vs 34 [IQR, 20-60] minutes for LAD; P = 0.018) and LCX CTOs required more contrast administration (280 [IQR, 210-370] mL vs 250 [IQR, 184-350] mL for RCA and 280 [IQR, 200-400] mL for LAD).",
            "output": [
                "Is percutaneous intervention of circumflex chronic total occlusions associated with worse procedural outcomes : insights from a Multicentre US Registry?"
            ]
        },
        {
            "id": "task847-c19a71c4ad5f4177abb40c5a72e7ac63",
            "input": "To determine the effects of supplemental fiber on plasma p-cresol, stool frequency, and quality of life (QoL) in chronic kidney disease (CKD) patients.', 'In a 12-week single-blind study, participants were provided with control muffins and supplements (5.5\\xa0g sucrose/day) for 2\\xa0weeks, muffins containing 10\\xa0g/day pea hull fiber and control supplements for 4\\xa0weeks, and muffins with 10\\xa0g/day pea hull fiber and 15\\xa0g/day inulin as a supplement for 6\\xa0weeks.', 'Individuals with CKD (n\\xa0=\\xa013; 6 males, 7 females; aged 65\\xa0\u00b1\\xa03\\xa0years; estimated glomerular filtration rate <50\\xa0mL/minute/1.73(2)) completed the study.', 'Plasma p-cresol was determined by gas chromatography-mass spectrometry, stool frequency by 5-day journals, and QoL by the KDQOL-36\u2122.', 'Plasma p-cresol decreased from 7.25\\xa0\u00b1\\xa01.74\\xa0mg/L during week 1 to 5.82\\xa0\u00b1\\xa01.72\\xa0mg/L during week 12 (P\\xa0<\\xa0.05), and in participants with high compliance (>70% inulin intake), from 6.71\\xa0\u00b1\\xa01.98\\xa0mg/L to 4.22\\xa0\u00b1\\xa01.16\\xa0mg/L (P\\xa0<\\xa0.05). Total fiber intake increased from 16.6\\xa0\u00b1\\xa01.7\\xa0g/day during control to 26.5\\xa0\u00b1\\xa02.4\\xa0g/day (P\\xa0<\\xa0.0001) with the added pea hull and to 34.5\\xa0\u00b1\\xa02.2\\xa0g/day with pea hull and inulin (P\\xa0<\\xa0.0001). Stool frequency increased from 1.4\\xa0\u00b1\\xa00.2 stools/day during control to 1.9\\xa0\u00b1\\xa00.3 stools/day during both fiber periods (P\\xa0<\\xa0.05). No change in overall QoL was observed.",
            "output": [
                "Does fiber supplementation lower plasma p-cresol in chronic kidney disease patients?"
            ]
        },
        {
            "id": "task847-c76a92a421b341fc99615046b43ff3c0",
            "input": "Our goal was to analyze the association of the level of antiphospholipid antibodies (aPLs) with stroke severity and outcome in patients with antiphospholipid syndrome (APS).', 'Observational study included consecutive patients with ischemic stroke younger than 55 years (2007-2012). We analyzed serum levels of aPLs, including anticardiolipin (aCL) antibodies, anti-\u03b22-glycoprotein I antibodies (anti-\u03b22GPI) and antiprothrombin antibodies (aPS/PT) within the first 48\\u2009h after admission, and again, in the case of a positive result, at least 12 weeks after the first measurement. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS), and the three-month stroke outcome by the modified Rankin Scale (mRS). Multiple linear regression models were used to analyze the correlation between the aPLs and stroke severity and outcome.', 'Overall 255 stroke patients were included, 22 (8.6%) with APS. Among them, a positive correlation was found between immunoglobulin M (IgM) aCL levels within 48\\u2009h and NIHSS (rho\\u2009=\\u20090.471; p\\u2009=\\u20090.027), as well as a tendency toward a positive correlation between immunoglobulin G (IgG) anti-\u03b22GPI levels within 48\\u2009h and three-month mRS (rho\\u2009=\\u20090.364; p\\u2009=\\u20090.096). Multiple linear regression analyses showed a positive correlation between levels of IgM aCL\\u2009<\\u200948\\u2009h and the NIHSS (\u03b2-coefficient [standard error; SE]\\u2009=\\u20090.127 [0.044]), as well as the levels of IgG anti-\u03b22GPIwithin 48\\u2009h and the three-month mRS (\u03b2-coefficient [SE]\\u2009=\\u20090.034 [0.011]).",
            "output": [
                "Do antiphospholipid antibodies correlate with stroke severity and outcome in patients with antiphospholipid syndrome?"
            ]
        },
        {
            "id": "task847-5e6941431e58438a895fa3226c6b4265",
            "input": "Young people in Tanzania are known to access reproductive health services from a range of close-to-community providers outside formal health settings such as drug stores, village AIDS committees, traditional healers and traditional birth attendants (TBAs). However, questions remain about the quality of services such agents provide. This study investigated their capacity to provide adolescent reproductive health (ARH) services and explored their readiness and ability to integrate with the mainstream health sector through community referral interventions.', 'Thirty-five focus group discussions exploring close-to-community provider experiences and attitudes to ARH service provision were carried out in two districts in Northern Tanzania. Discussions were conducted in Kiswahili, digitally recorded, verbatim-transcribed, translated and back-translated from Swahili to English. A thematic analysis was conducted using NVivo 9.', 'The major close-to-community cadres providing reproductive health services were drug stores, traditional healers, TBAs and village health workers. They reported being the first port of call for adolescents seeking reproductive health services, but their knowledge of ARH needs was poor. They had negative attitudes to, and lacked the necessary resources for, the provision of such services for adolescents. Some were particularly unwilling to provide condom services and were prejudiced against adolescents using them. There was poor integration between the close-to-community providers and the formal health sector, further limiting their ability to provide adequate services.",
            "output": [
                "Are `` There bugs in condoms '' : Tanzanian close-to-community providers ' ability to offer effective adolescent reproductive health services?"
            ]
        },
        {
            "id": "task847-1c14f9b48e304812b4ca4b93aae7da96",
            "input": "To investigate how affects electrical-conduction function following myocardial infarction (MI) in rats.', 'Thirty SD rats of either sex (220-250 g) were anesthetized using chlorine hydrate and were randomly divided into three groups: control group, MI group and transplantation group. The field potential (FP) morphology and activation-conduction duration were recorded with microeletrode array techniques.', 'The MEA recorded clear FP morphology. Activation-conduction duration was (6.5 \u00b1 2.12) ms in the control group, (17.5 \u00b1 3.54) ms in the MI group, and (9.13 \u00b1 1.31) ms in the transplantation group.",
            "output": [
                "Does engineered heart tissue transplantation alter electrical-conduction function in rats with myocardial infarction?"
            ]
        },
        {
            "id": "task847-a5c37a8a9fe34cd999eec1d51b0f69d3",
            "input": "Protein kinase D (PKD or PKD1) is a serine/threonine protein kinase that has been shown to play a role in a variety of cellular processes; however, the function of PKD1 in the skin has not been fully investigated. The balance between proliferation and differentiation processes in the predominant cells of the epidermis, the keratinocytes, is essential for normal skin function.', 'To investigate the effect of PKD1 deficiency on proliferation and differentiation of epidermal keratinocytes.', 'We utilized a floxed PKD1 mouse model such that infecting epidermal keratinocytes derived from these mice with an adenovirus expressing Cre-recombinase allowed us to determine the effect of PKD1 gene loss in vitro. Proliferation and differentiation were monitored using qRT-PCR, Western blot, transglutaminase activity assays, [3H]thymidine incorporation into DNA and cell cycle analysis.', 'A significant decrease in PKD1 mRNA and protein levels was achieved in adenoviral Cre-recombinase-infected cells. Deficiency of PKD1 resulted in significant increases in the mRNA and protein expression of various differentiation markers such as loricrin, involucrin, and keratin 10 either basally and/or upon stimulation of differentiation. PKD1-deficient keratinocytes also showed an increase in transglutaminase expression and activity, indicating an anti-differentiative role of PKD1. Furthermore, the PKD1-deficient keratinocytes exhibited decreased proliferation. However, PKD1 loss had no effect on stem cell marker expression.",
            "output": [
                "Does protein kinase D1 deficiency promote differentiation in epidermal keratinocytes?"
            ]
        },
        {
            "id": "task847-5152cc59c70c44c78c222c9a983645a5",
            "input": "Cancer stem cells (CSC) was reported to play an important role in various kinds of cancer. CD133 is one of the cancer stem cell markers in solid cancers. However, the correlation between CD133 expression and the clinicopathological factors in colorectal cancer (CRC) remains unclear.', 'Forty patients with CRC who underwent operations were enrolled. Expression of CD133 was investigated by immunohistochemistry (IHC). The staining was observed in the cytoplasm of cancer cells and the patients who have the staining were defined as CD133-positive cases. The patients were divided into two groups: the CD133-positive group (n = 22) and negative group (n = 18). Clinicopathological factors were compared between the two groups. The prognostic factors were investigated by multivariate analysis.', 'In the CD133-positive group, the incidence of lymph node and liver metastasis, lymphatic and venous invasion, as well as the progression of stage of cancer were higher than that in the CD133-negative group. The 5-year survival rate and the disease-free survival rate in the CD133-positive group were lower than that in the CD133-negative group. The multivariate analysis revealed that CD133 expression tended to be an independent prognostic factor.",
            "output": [
                "Is cD133 expression correlated with poor prognosis in colorectal cancer?"
            ]
        },
        {
            "id": "task847-277749fc2c524e058c1199eb5ac943ca",
            "input": "Mice with functional ablation of the neurokinin-1 receptor gene (NK1R(-/-)) display behavioural abnormalities which resemble the hyperactivity, inattention and impulsivity seen in Attention Deficit Hyperactivity Disorder (ADHD). Here, we investigated whether the established ADHD treatment, atomoxetine, alleviates these abnormalities when tested in the light/dark exploration box (LDEB) and 5-Choice Serial Reaction-Time Task (5-CSRTT).', 'Separate cohorts of mice were tested in the 5-CSRTT and LDEB after treatment with no injection, vehicle or atomoxetine (5-CSRTT: 0.3, 3 or 10mg/kg; LDEB: 1, 3 or 10mg/kg).', 'Atomoxetine reduced the hyperactivity displayed by NK1R(-/-) mice in the LDEB at a dose (3mg/kg) which did not affect the locomotor activity of wildtypes. Atomoxetine (10mg/kg) also reduced impulsivity in NK1R(-/-) mice, but not wildtypes, in the 5-CSRTT. No dose of drug affected attention in either genotype.",
            "output": [
                "Does atomoxetine reduce hyperactive/impulsive behaviours in neurokinin-1 receptor 'knockout ' mice?"
            ]
        },
        {
            "id": "task847-be6271e6168e444b8751c2a4415fc38d",
            "input": "Irinotecan (CPT-11), a highly effective chemotherapeutic agent, can cause severe neutropenia and diarrhea. The area under the curve of plasma levels over time of SN-38, an active metabolite of CPT-11, was previously reported to correlate with the pre-treatment serum total bilirubin level (PTB). However, there are no established criteria for selecting CPT-11 dose on the basis of PTB. Therefore, we evaluated PTB as an indicator for the optimal CPT-11 dose.', 'Retrospective analyses were conducted in patients administered CPT-11 as a single agent at the Osaka National Hospital from June 2006 to July 2013. Data obtained during the first 28 days following CPT-11 administration were analyzed to compare PTB between patients with and without grade 3-4 neutropenia and grade 3-4 diarrhea. Receiver operating characteristics (ROC) curve analysis was performed to determine the optimal PTB cutoff value for PTB-associated toxicity. Subgroup analysis was performed comparing the incidence of toxicity in patients with PTB values below or above the cutoff value.', 'Although PTB incidence was significantly higher in patients who developed grade 3-4 neutropenia than in those who did not, PTB was not associated with grade 3-4 diarrhea. The PTB cutoff value for association with grade 3-4 neutropenia occurrence was set at 0.8 mg/dL. The incidence of febrile neutropenia (FN) significantly elevated to 21% in patients with PTB \u22650.8 mg/dL, whereas that of patients with PTB <0.8 mg/dL was 4%. In the subgroup analysis, no difference was found in the neutropenia incidence between patients treated with a dose below 80 mg/m(2) and those treated on a weekly schedule.",
            "output": [
                "Do pre-treatment serum total bilirubin level as an indicator of optimal CPT-11 dosage?"
            ]
        },
        {
            "id": "task847-8635ece0ce614a37b1b2ed3b84d6f926",
            "input": "Nonalcoholic steatohepatitis (NASH) is associated with cirrhosis and hepatocellular carcinoma. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play key roles in the development of the disease. However, the therapeutic target of NASH has not been fully defined and new treatments are needed. We investigated the protective effects of the antioxidant indole-derived NecroX-7 in a NASH mouse model using leptin-deficient ob/ob and methionine- and choline-deficient (MCD) diet-fed ob/ob mice.', 'Six-week-old male mice were divided into three groups: ob/+ mice, ob/ob mice treated with vehicle and ob/ob mice treated daily with NecroX-7 (20 mg/kg) for 4 weeks. To study the effects of NecroX-7 in a fibrosis model, NASH was induced by feeding ob/ob mice an MCD diet. The effects of NecroX-7 on NASH progression were evaluated using biochemical, histological and molecular markers.', 'NecroX-7-treated ob/ob mice had a marked decrease in serum aspartate aminotransferase and alanine transaminase compared with vehicle-treated controls. Interestingly, hepatic steatosis and lipid peroxidation were significantly improved by NecroX-7 treatment. NecroX-7 inhibited tert-butylhydroperoxide- and H2 O2 -induced mitochondrial ROS/RNS in primary hepatocytes and attenuated mitochondrial dysfunction in vitro and in vivo. Furthermore, NecroX-7-treated mice exhibited fewer infiltrating macrophages and reduced hepatic tumour necrosis factor-alpha expression. Hepatic fibrosis in MCD-fed ob/ob mice was significantly decreased by NecroX-7 treatment.",
            "output": [
                "Does the indole derivative NecroX-7 improve nonalcoholic steatohepatitis in ob/ob mice through suppression of mitochondrial ROS/RNS and inflammation?"
            ]
        },
        {
            "id": "task847-147dbcc92cb34a4289f8c293c949b55e",
            "input": "The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour.', 'Intestinal organoids were transferred into Matrigel\u00ae mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence.', 'We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids.",
            "output": [
                "Does fluorescent labelling of intestinal epithelial cells reveal independent long-lived intestinal stem cells in a crypt?"
            ]
        },
        {
            "id": "task847-a10766926d4145a499234ad871ca34dd",
            "input": "There are two opposing possibilities for the main pathogenesis of trauma-induced coagulopathy: an acute coagulopathy of trauma shock and disseminated intravascular coagulation with the fibrinolytic phenotype.', 'The objective of this study was to clarify the main pathogenesis of trauma-induced coagulopathy using a rat model of Noble-Collip drum trauma.', 'Eighteen rats were divided into the control, trauma 0, and trauma 30 groups. The trauma 0 and 30 groups were exposed to Noble-Collip drum trauma. Blood samples were drawn without, immediately after, and 30 min after Noble-Collip drum trauma in the control, trauma 0, and trauma 30 groups, respectively. Coagulation and fibrinolysis markers were measured. Thrombin generation was assessed according to a calibrated automated thrombogram.', 'Spontaneous thrombin bursts resulting from circulating procoagulants were observed in the nonstimulated thrombin generation assay immediately after trauma. Soluble fibrin levels (a marker of thrombin generation in the systemic circulation) were 50-fold greater in the trauma groups than in the control group. The resultant coagulation activation consumed platelets, coagulation factors, and antithrombin. Endogenous thrombin potential and factor II ratio were significantly negatively correlated with antithrombin levels, suggesting insufficient control of thrombin generation by antithrombin. High levels of active tissue-type plasminogen activator induced hyperfibrin(ogen)olysis. Soluble thrombomodulin increased significantly. However, activated protein C levels did not change.",
            "output": [
                "Does noble-Collip Drum Trauma induce Disseminated Intravascular Coagulation But Not Acute Coagulopathy of Trauma-Shock?"
            ]
        },
        {
            "id": "task847-6d6519829e5a4861977efa2f62ef193f",
            "input": "Aminoguanidine (AG), a well known inhibitor of advanced glycation end products, has been reported to attenuate cardiac hypertrophy and fibrosis. However, the underlying mechanism by which AG exerts its anti-fibrotic activity is not well understood. Reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) are implicated as playing a major role in the development of cardiac fibrosis. Hence, the present study was designed to investigate the effect of AG on ROS generation and MMPs during the progress of hypertrophic growth.', 'Isoproterenol (ISO) (7 mg/kg/day, s.c., for 15 days) was used to induce cardiac hypertrophy in experimental adult Wistar rats. ISO-treated rats were co-treated with AG (50 mg/kg/day, i.p., for 15 days). Ventricular collagen deposition, gelatinase activity of MMP-2 and MMP-9, and the level of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were investigated. In addition, in silico docking of MMP-2 and MMP-9 proteins, ROS generation, and nuclear translocation of NF-\u03baB-p65 were also studied.', 'AG co-treatment markedly attenuated the ISO-induced hypertrophic growth and fibrosis. Heart-weight-to-body weight ratio and ventricular collagen levels were normalized upon AG co-treatment. A significantly decreased level of ventricular ROS generation (p < 0.001) and NF-\u03baB-p65 nuclear translocation was observed in the rat hearts co-treated with AG. Furthermore, in silico docking analysis revealed that AG interacts at the active site of MMP-2 and MMP-9.",
            "output": [
                "Does aminoguanidine inhibit ventricular fibrosis and remodeling process in isoproterenol-induced hypertrophied rat hearts by suppressing ROS and MMPs?"
            ]
        },
        {
            "id": "task847-554a9d3e8b7646249892e2ade6336513",
            "input": "With the advent of laparoscopic surgery, more choledochal cysts are excised laparoscopically. In this study, we compared the outcomes from laparoscopic hepaticojejunostomy (HJ) and hepaticoduodenostomy (HD) for biliary-enteric reconstruction.', 'A retrospective analysis of patients who had undergone laparoscopic choledochal cyst excision between February 2005 and January 2014 in a tertiary referral centre was performed. Demographics data, operative techniques and surgical outcomes were analysed according to the way of biliary-enteric reconstruction.', 'A total of 31 patients were identified, 20 of whom underwent HJ and 11 underwent HD. There were no significant differences in terms of demographics. Median operative time was significantly shorter in HD group (211.0\\xa0\u00b1\\xa096.4 vs. 386.0\\xa0\u00b1\\xa090.4\\xa0min, p\\xa0=\\xa00.001). Although postoperative enteral feeding was initiated later in HD group (5.0\\xa0\u00b1\\xa00.8 vs. 4.0\\xa0\u00b1\\xa03.6\\xa0days, p\\xa0=\\xa00.036), postoperative stay in intensive care unit (ICU) (0.7\\xa0\u00b1\\xa01.0 vs. 2.4\\xa0\u00b1\\xa01.7\\xa0days, p\\xa0=\\xa00.007) and overall hospital stay (9.1\\xa0\u00b1\\xa01.0 vs. 14.4\\xa0\u00b1\\xa012.2\\xa0days, p\\xa0=\\xa00.157) favoured HD group. There was no perioperative mortality. Median follow-up duration was 24.0 (\u00b111.0) months in HD group and 67.5 (\u00b123.7) months in HJ group. One patient in HJ group had postoperative cholangitis related to anastomotic stricture whereas no cholangitis noted in HD group. In total, five patients in HJ group required second operation for complications and residual diseases whereas none in HD group required reoperation.",
            "output": [
                "Is biliary-enteric reconstruction with hepaticoduodenostomy following laparoscopic excision of choledochal cyst associated with better postoperative outcomes : a single-centre experience?"
            ]
        },
        {
            "id": "task847-ee756206c5cd49e792c7b45ec6fb30d3",
            "input": "It has been proposed that nutritional therapy in critically ill patients after major burn reduces mortality. However, the actual practice of nutrient delivery, and the effect on outcome, has not been described.', 'To evaluate international practices related to nutritional support and outcomes in mechanically ventilated patients with burn injury.', 'Data from the International Nutrition Surveys (2007-2011) for patients with a primary diagnosis of burn were extracted and analysed.', 'Eighty-eight of 90 patients (aged 16-84 years) received enteral nutrition. The median time for initiation of enteral feeding was 17 h [range 0-65]. Fifty patients (57%) had interruptions to nutrient delivery, most often these interruptions were fasting for operative procedures. There were substantive energy and protein deficits [943 (654) kcal/day and 49 (41) g/day, respectively; mean (SD)]. Nineteen (21%) patients died within 60 days of admission, and the energy and protein deficits were greater in those that died compared with survivors [died vs. survived, energy: 1251 (742) vs. 861 (607) kcal/d; p=0.02; and protein 67(42) vs. 44(39) g/d; p=0.03]. Energy and protein deficits were associated with increased mortality with the greater the deficit, the stronger the association with death (odds ratio for death: energy deficit/100 kcal 1.10 (1.01, 1.19); p=0.028 and protein/10 g 1.16 (1.01, 1.33); p=0.037). Results were similar and remained significant after adjusting for severity of illness.",
            "output": [
                "Do international observational study of nutritional support in mechanically ventilated patients following burn injury?"
            ]
        },
        {
            "id": "task847-5fb600dcdb814d749c80e67b254e2f79",
            "input": "Oxidative stress plays an important role in Alzheimer's disease (AD) etiopathogenesis. There were several studies that showed impaired antioxidant defense system (ADS) enzymes expression or activity in AD patients. There are only few studies evaluating the importance of ADS gene single nucleotide polymorphisms (SNPs) as risk factors of AD. We evaluated association between chosen SNPs of the enzymes of the ADS and risk of AD.\", 'We included 400 AD patients and 402 healthy controls. We studied rs1041740, rs4998557 and rs2070424 of the SOD1 gene, rs2855116, rs5746136 and rs4880 of the SOD2 gene and rs3448, rs1050450 and rs1800668 of the GPx-1 gene (real time PCR). To determine the APOE gene common polymorphism, two single-nucleotide polymorphisms (SNPs; NCBI SNPs rs429358 and rs7412) were genotyped (TaqMan assays, Applied Biosystems [ABI], Foster City, CA, USA). The genotype and gender frequencies were compared between the studied groups by the \u03c7(2) test and mean age by the t-Student test.', 'Among all studied SNPs only rs2070424 of the SOD1 gene was a protective factor for AD in an additive (OR=0.47; 95% CI=0.30-0.74, p=0.001) and recessive (OR=0.47; 95% CI=0.30-0.75, p=0.002) models including age, gender and APOE gene status.",
            "output": [
                "Is rs2070424 of the SOD1 gene associated with risk of Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-e96bc7dc17b04c0bb324466cedd354f8",
            "input": "Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood.', 'We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis.', 'SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree.",
            "output": [
                "Is structural maintenance of chromosomes 4 a predictor of survival and a novel therapeutic target in colorectal cancer?"
            ]
        },
        {
            "id": "task847-3a5c16bb82694c1a94958a0702b4f704",
            "input": "Nestin is a type VI intermediate filament protein known as a marker for progenitor cells that can be mostly found in tissues during the embryonic and fetal periods. In our study, we aimed to determine the expression of nestin in meninges covering the brain tissue at different developmental stages and in the new born.', 'In this study 10 human fetuses in different development stages between developmental weeks 9-34 and a newborn brain tissue were used. Fetuses in paraffin section were stained with H+E and nestin immunohistochemical staining protocol was performed.', 'In this study, in the human meninges intense nestin expression was detected as early as in the 9th week of development. Intensity of this expression gradually decreased in later stages of development and nestin expression still persisted in a small population of newborn meningeal cells.",
            "output": [
                "Is intermediate filament protein nestin expressed in developing meninges?"
            ]
        },
        {
            "id": "task847-37a9349833b044e18b34a5ccd16d1540",
            "input": "To compare the safety and efficacy of patients undergoing dorsal penile plication with patients undergoing ventral and lateral plication.', 'A retrospective review was performed of all patients who underwent penile plication between 2007 and 2013. Plication was performed through a 2-cm longitudinal incision in the proximal or midpenile shaft without degloving. Plication sutures were placed in parallel opposite the angle of greatest curvature. Dorsal plication was performed with minimal displacement of the neurovascular bundle. Patient demographics, perioperative outcomes, and patient-reported outcomes were analyzed.', 'Of 215 patients who underwent penile plication, complete operative and patient-reported outcomes data were available for 118 (55%). Patients were grouped by location of plication: dorsal (n = 17 [14%]), ventral (n = 65 [55%]), and lateral (n = 36 [31%]). Mean age (52-58 years; P = .51) and preoperative curvature (36-51\u00b0; P = .78) were similar among the 3 groups. Each group required a similar number of sutures (8-9; P = .18) to achieve similar correction (37-45\u00b0; P = .33). Patients completed a satisfaction survey at a mean of 15 months (range, 1-41 months) after surgery. All groups reported equally high rates of satisfaction for penile curvature (P = .64), penile rigidity (P = .64), strength of erection (P = .98), and overall satisfaction (P = .75). Although each group reported subjective decrease in penile length (P = .10), objective length loss occurred on a small scale (mean length loss for all groups, 0.3-0.8 cm; P = .24).",
            "output": [
                "Is dorsal plication without degloving safe and effective for correcting ventral penile deformities?"
            ]
        },
        {
            "id": "task847-784b3bab282d4f8ea0d846004f4c3770",
            "input": "The objective of the study was to evaluate work disability and its main associated factors in patients with early arthritis. Argentine Consortium for Early Arthritis (CONAART) is the first early arthritis cohort in Argentina. Patients with one or more swollen joints and less than 2 years of symptoms duration were followed up prospectively in 13 departments of rheumatology. Social, demographic, familiar, clinical, and laboratory data were recollected. At first year and every year, X-rays of hands and feet were performed and working status and pharmaco-economic data were recollected. Work status (employed, unemployed, retired) and type of work were assessed by direct interview using a predesigned questionnaire. Eight hundred forty-eight patients were included, rheumatoid arthritis (RA)\\u2009=\\u2009483 (57 %)and undifferentiated arthritis (UA)\\u2009=\\u2009365 (43 %), 694 (81.8 %) were women, median age was 46 years (interquartile range (IQR) 35-55.7) and median symptoms duration 7 months (IQR 3-12). Patients with RA had significantly higher disease activity, worse functional capacity and quality of life, and more severe radiological damage compared to UA patients. However work disability (unemployed patient) was comparable between groups (RA\\u2009=\\u200921 % versus UA\\u2009=\\u200918.6 % p\\u2009=\\u2009NS). In both groups, unemployed patients had higher disease activity score of 28 joints (DAS28), worse Health Assessment Questionnaire (HAQ) values, and less years of formal education (p value <0.005 in all comparisons). Radiological damage was greater in unemployed patients but this difference did not reach statistical significance. In multivariate analysis, disease activity was the main variable associated with unemployment in both groups. Joint involvement was the main cause of work disability in this cohort of patients with early arthritis, independently of the final diagnosis.",
            "output": [
                "Is work disability related to the presence of arthritis and not to a specific diagnosis . Results from a large early arthritis cohort in Argentina?"
            ]
        },
        {
            "id": "task847-41eea92721694d168c6f0f42e7f75743",
            "input": "Central giant cell lesion (CGCL) and giant cell tumour (GCT) are bone lesions that share similar microscopic features. Recently, it was reported that 90% of bone GCT exhibit either p.Gly34 Trp or p.Gly34 Leu in H3F3A, one of two genes for histone H3.3 located on chromosome 1. We aimed to test whether sporadic CGCL of the jaws share the H3F3A mutations reported in GCT of other bones.', 'Nine samples of CGCL of the jaws were included in the study, and mutations were assessed by direct sequencing.', 'None of the CGCL samples presented the recurrent p.Gly34 Trp or p.Gly34 Leu mutations in the H3F3A gene.",
            "output": [
                "Is the highly prevalent H3F3A mutation in giant cell tumours of bone shared by sporadic central giant cell lesion of the jaws?"
            ]
        },
        {
            "id": "task847-3e59299cf1ef4e099eb04a39c6a52ad9",
            "input": "Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized as the incomplete resolution of emboli after pulmonary embolism (PE) and the subsequent fibrotic organization and remodeling of pulmonary vascular bed. It has been reported that abnormal fibrin probably contributes to the incomplete resolution of emboli. And there is evidence that free iron could convert fibrinogen into fibrin which is remarkably resistant to lysis. Thus, we hypothesized that persistent iron overload might participate in the development of CTEPH.', 'A case-control study was conducted. Forty-five CTEPH patients were enrolled as cases, and 36 age and sex frequency-matched chronic PE patients without pulmonary hypertension were selected as controls. Levels of free iron, soluble transferrin receptor (sTfR), ferritin, sTfR/ferritin ratio, hepcidin-25, tumor necrosis factor-alpha (TNF-\u03b1), interleukin (IL)-6, and malondialdehyde (MDA) were compared between the two groups. Logistic regression analysis was carried out to estimate odds ratios.', \"There was no difference of the levels of free iron, hepcidin-25, sTfR, ferritin, sTfR/ferritin ratio, TNF-\u03b1, and MDA between CTEPH patients and the controls. Levels of sTfR and ferritin in both groups were within the normal limits. Levels of IL-6 in CTEPH patients were significantly higher than that in the controls. A negative correlation was observed between hepcidin-25 and sTfR (Spearman's r=-0.438, P<.001), and a positive correlation was observed between hepcidin-25 and ferritin (Spearman's r=0.503, P<.001). In the univariate logistic regression model, there was no association observed between CTEPH and free iron, hepcidin-25, sTfR, ferritin, sTfR/ferritin ratio, TNF-\u03b1, IL-6, and MDA.",
            "output": [
                "Is chronic thromboembolic pulmonary hypertension associated with iron overload?"
            ]
        },
        {
            "id": "task847-f1688d0b4baf482eafdbc82666e49f05",
            "input": "The mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease.', 'To characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls.', 'This was a non-interventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3\\xa0days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post-visit 2\\xa0weeks later. The sinonasal outcome test-22 (SNOT-22) scores and immunological parameters in the specimens were analysed using a novel, unsupervised learning method and by conventional univariate analysis.', 'Both CRSwNP patients and control subjects showed a significant increase in SNOT-22 scores during acute exacerbation. Increased nasal levels of IL-6, IL-5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM-CSF levels were notable and were validated by a conventional analysis.",
            "output": [
                "Does immunological profiling in chronic rhinosinusitis with nasal polyps reveal distinct VEGF and GM-CSF signatures during symptomatic exacerbations?"
            ]
        },
        {
            "id": "task847-752ed154515048e5a57e9e7d56fcba61",
            "input": "Little is known about endothelial function in adolescents with type 1 diabetes, and we evaluated endothelial dysfunction, using reactive hyperaemia peripheral arterial tonometry (RH-PAT).', 'This prospective, observational, 1-year study focused on 73 adolescents with type 1 diabetes, using multiple daily injections or continuous subcutaneous insulin infusion. The subjects were assessed using RH-PAT, body mass index, blood pressure, fasting lipid profile, glycated haemoglobin, insulin requirements and hours of physical exercise per week.', 'Endothelial dysfunction was observed in 56 patients (76.7%), with lower mean RH-PAT scores (1.26\\xa0\u00b1\\xa00.22 versus 2.24\\xa0\u00b1\\xa00.48, p\\xa0<\\xa00.0001) and higher glycated haemoglobin values at baseline (8.27\\xa0\u00b1\\xa01.24% versus 7.37\\xa0\u00b1\\xa00.54%, p\\xa0=\\xa00.006) and as a mean of the whole period since diagnosis (8.25\\xa0\u00b1\\xa01.22% versus 7.72\\xa0\u00b1\\xa00.82%, p\\xa0=\\xa00.034). A higher percentage of patients with endothelial dysfunction showed abnormal cardiac autonomic tests (p\\xa0=\\xa00.02) and were more sedentary, exercising <4 hours a week, than patients with normal endothelial function. After follow-up in 64/73 patients, we observed endothelial dysfunction in 81.8% of patients, despite a modest improvement in glycated haemoglobin.",
            "output": [
                "Do adolescents and young adults with type 1 diabetes display a high prevalence of endothelial dysfunction?"
            ]
        },
        {
            "id": "task847-7a0f5d50a5bb431085d23c2048fc1f51",
            "input": "Induction of delayed hypersensitivity reactions by red tattoos has been occasionally reported. Little is known about the inks used. Azo pigments have been implicated in some instances, but there is only one reported case involving quinacridones.', 'To describe the clinical and pathological features and outcome of skin reactions induced by red tattoo pigments.', 'Six patients with a cutaneous reaction induced by a red tattoo pigment underwent biopsy and prick and patch testing with the inks supplied.', 'We observed seven reactions in the 6 patients. Histology showed various patterns: three lichenoid, two eczematous, and two pseudolymphomatous. Five reactions occurred with azo pigments, and two with quinacridones, in both cases with Violet 19 and Red 122. Four inks were tested. Only one patch test gave a positive result at a late reading (day 7). Prick tests gave negative results. The reactions required various treatments, including laser treatment for 2 patients. Activation of the reaction in 1 case was transient.",
            "output": [
                "Do azo pigments and quinacridones induce delayed hypersensitivity in red tattoos?"
            ]
        },
        {
            "id": "task847-2f0fe716e62b4e13a3c4801c03bd9a78",
            "input": "The current American Joint Committee on Cancer Seventh Edition (AJCC7) pathologic staging for esophageal adenocarcinoma (EAC) is derived from data assessing the outcomes of patients having undergone esophagectomy without neoadjuvant treatment and has unclear significance in patients who have received multimodality therapy. Lymph nodes with evidence of neoadjuvant treatment effect without residual cancer cells may be observed and are not traditionally considered in pathologic reports, but may have prognostic significance.', 'All patients who underwent esophagectomy after completing neoadjuvant therapy for EAC at our institution between 2006 and 2012 were reviewed. Slides of pathologic specimens were reexamined for locoregional treatment-response nodes lacking viable cancer cells but with evidence of acellular mucin pools, central fibrosis, necrosis, or calcifications suggesting prior tumor involvement. Kaplan-Meier survival functions were estimated, and Cox proportional hazards regression models were used to compare staging models.', 'Ninety patients (82 men) underwent esophagectomy after neoadjuvant therapy for EAC (mean age, 61.8 \u00b1 8.9 years). All patients received preoperative chemotherapy, and 50 patients also underwent preoperative radiotherapy. Median Kaplan-Meier survival was 55.6 months, and 5-year survival was 35% (95% confidence interval, 19% to 62%). A total of 100 treatment-response nodes were found in 38 patients. For patients with limited nodal disease (62 ypN0-N1), the presence of treatment-response nodes was associated with significantly worse survival (p = 0.03) compared with patients lacking such nodes. Adjusting for patient age and AJCC7 pathologic stage showed the presence of treatment-response nodes significantly increased the risk of death (hazard ratio, 2.7; 95% confidence interval, 1.1 to 6.9; p = 0.04). When stage-adjusted survival was modeled, counting treatment-response nodes as positive nodes offered a better model fit than ignoring them.",
            "output": [
                "Is neoadjuvant treatment response in negative nodes an important prognosticator after esophagectomy?"
            ]
        },
        {
            "id": "task847-2ffea6cc450b4f56bfc19c077dccc543",
            "input": "Aortic valve interstitial cells (AVICs) have been implicated in the pathogenesis of calcific aortic valve disease. Signal transducer and activator of transcription 3 (Stat3) possesses antiinflammatory effects. Given that calcification occurs in adult valves, we hypothesized that AVICs from adult valves more likely undergo a proosteogenic phenotypic change than those from pediatric valves and that may be related to different Stat3 activation in the response of those two age groups to toll-like receptor 4 (TLR4).', 'AVICs from healthy human aortic valve tissues were treated with TLR4 agonist lipopolysaccharide. Cellular levels of TLR4, intercellular adhesion molecule 1, bone morphogenetic protein 2, and alkaline phosphatase, as well as phosphorylation of p-38 mitogen-activated protein kinase (MAPK), nuclear factor-\u03ba\u03b2 (NF-\u03ba\u03b2), and Stat3, were analyzed.', 'Toll-like receptor 4 protein levels were comparable between adult and pediatric AVICs. Adult cells produce markedly higher levels of the above markers after TLR4 stimulation, which is negatively associated with phosphorylation of Stat3. Inhibition of Stat3 enhanced p-38 MAPK and NF-\u03ba\u03b2 phosphorylation and exaggerated the expression of the above markers in pediatric AVICs after TLR4 stimulation.",
            "output": [
                "Do adult aortic valve interstitial cells have greater responses to toll-like receptor 4 stimulation?"
            ]
        },
        {
            "id": "task847-9e8cc67dae6a42f982208b51645f28db",
            "input": "In flowering plants, fertilization relies on the delivery of the sperm cells carried by the pollen tube to the ovule. During the tip growth of the pollen tube, proper assembly of the cell wall polymers is required to maintain the mechanical properties of the cell wall. Xyloglucan (XyG) is a cell wall polymer known for maintaining the wall integrity and thus allowing cell expansion. In most angiosperms, the XyG of somatic cells is fucosylated, except in the Asterid clade (including the Solanaceae), where the fucosyl residues are replaced by arabinose, presumably due to an adaptive and/or selective diversification. However, it has been shown recently that XyG of Nicotiana alata pollen tubes is mostly fucosylated. The objective of the present work was to determine whether such structural differences between somatic and gametophytic cells are a common feature of Nicotiana and Solanum (more precisely tomato) genera.', 'XyGs of pollen tubes of domesticated (Solanum lycopersicum var. cerasiforme and var. Saint-Pierre) and wild (S. pimpinellifolium and S. peruvianum) tomatoes and tobacco (Nicotiana tabacum) were analysed by immunolabelling, oligosaccharide mass profiling and GC-MS analyses.', 'Pollen tubes from all the species were labelled with the mAb CCRC-M1, a monoclonal antibody that recognizes epitopes associated with fucosylated XyG motifs. Analyses of the cell wall did not highlight major structural differences between previously studied N. alata and N. tabacum XyG. In contrast, XyG of tomato pollen tubes contained fucosylated and arabinosylated motifs. The highest levels of fucosylated XyG were found in pollen tubes from the wild species.",
            "output": [
                "Do pollen tube cell walls of wild and domesticated tomatoes contain arabinosylated and fucosylated xyloglucan?"
            ]
        },
        {
            "id": "task847-def7ec26607f4278b3d99d2feb532b63",
            "input": "Before guidelines were issued, many patients with hepatitis B flare and hepatic decompensation had discontinued lamivudine therapy instead of indefinite therapy. We investigated their outcomes.', 'We performed a retrospective cohort study of 263 consecutive patients with chronic hepatitis B (94 with cirrhosis) who recovered from a flare of hepatitis with hepatic decompensation and were followed after cessation of lamivudine therapy. Clinical events that occurred during the follow-up period were assessed by chart review and analysis of results from retrospective assays.', 'The mean duration of lamivudine therapy was 12.1 \u00b1 8.6 months; data were collected from patients for 89.1 \u00b1 38.7 months after therapy ended. In the first year off therapy, 29.9% of patients had clinical relapse, 16.2% had hepatitis flares, and 8.2% had hepatic decompensation. There was no significant difference in the incidence of hepatic decompensation between patients with and without cirrhosis. Hepatocellular carcinoma developed in 14 patients 20-109 months after cessation of therapy, with 5-year cumulative incidence of 5.2% in patients with cirrhosis. Three patients with cirrhosis died of hepatic decompensation 38-76 months after cessation of therapy (5-year cumulative mortality, 2.9%). Multivariate analyses showed that men were more likely than women to have recurrence of hepatic decompensation (hazard ratio [HR], 4.339; P = .014). Liver cirrhosis (HR, 2.766; P = .041) and age (HR, 1.054; P = .023) increased risk for hepatocellular carcinoma.",
            "output": [
                "Do clinical events after cessation of lamivudine therapy in patients recovered from hepatitis B flare with hepatic decompensation?"
            ]
        },
        {
            "id": "task847-a6d65d38612b4fff88031a535f3c34c6",
            "input": "This study aims to characterize the function of downregulated MicroRNA miR-205 in renal cell carcinoma (RCC), and show how the downstream zinc finger E-box-binding homeobox 2 (ZEB2) is negatively regulated by miR-205.', 'The expression of miR-205 was detected in RCC and adjacent non-tumor tissues using real-time polymerase chain reaction (PCR). The expression of miR-205 and ZEB2 was detected in RCC cell lines using real-time PCR. The luciferase reporter assay was used to assess ZEB2 as a target of miR-205. Protein levels of ZEB2, E-cadherin, and vimentin were measured by western blot after overexpression of miR-205 in ACHN cells. In vivo functions of miR-205 in ACHN cells were measured by MTT assays, migration and invasion assays, and flow cytometry.', 'MiR-205 was significantly downregulated in RCC samples and cell lines compared with matched non-tumor tissues and HK-2 cells, respectively. No significant difference was found in miR-205 expression between well differentiated and poorly to moderately differentiated groups or between phase I and phase II-III. ZEB2 was upregulated in RCC cell lines compared with expression in HK-2 cells. Upregulation of miR-205 expression caused the downregulation of ZEB2 and vimentin, and the upregulation of E-cadherin in ACHN cells. miR-205 also inhibited proliferation, migration, and invasion, and induced apoptosis of ACHN cells.",
            "output": [
                "Is miRNA-205 a candidate tumor suppressor that targets ZEB2 in renal cell carcinoma?"
            ]
        },
        {
            "id": "task847-2a3e7da4d6b8440eae2834569657acb1",
            "input": "The aim of the present study was to explore the association of the functional single-nucleotide polymorphism (SNP) rs3746804 in C20orf54 with the susceptibility to esophageal squamous cell carcinoma (ESCC).', 'SNP rs3746804 in C20orf54 was detected by direct sequencing in 434 ESCC patients and 554 healthy controls from Shanxi and Henan Provinces in China, geographically a high incidence area for ESCC. The frequencies and distribution of TT, CT, and CC genotypes of SNP rs3746804 between those 2 cohorts were compared and its association with ESCC was assessed.', 'For SNP rs3746804 the genotype distribution of CT and CC in ESCC patients both significantly differed from those in healthy controls (p=0.002, 0.001, respectively), while the distribution of TT did not differ significantly between the groups (p=0.757). The ratio of T:C was high in healthy individuals and low in ESCC patients. Compared to genotype CC, both genotypes CT (odds ratio (OR)=0.63, 95% confidence interval (CI) 0.48l-0.826), and CT+TT (OR=0.654, 95% CI 0.507-0.844) were associated with significantly decreased risk for ESCC.",
            "output": [
                "Does the functional SNP rs3746804 in C20orf54 modify susceptibility to esophageal squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-f5409ccf95944042bf2be44efdc0e2f8",
            "input": "Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection.', 'In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation.', 'Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection.",
            "output": [
                "Does soluble CD30 predict late acute rejection or safe tapering of immunosuppression in renal transplantation?"
            ]
        },
        {
            "id": "task847-0e92f253603a42a9b9504ecee6168f12",
            "input": "Anemia of chronic disease, a cytokine-mediated anemia, is a frequent complication of many chronic inflammatory conditions. The present case-control study was aimed to evaluate levels of systemic hematological markers indicative of anemia in patients with generalized, severe, chronic periodontitis.', 'A convenience quota sample of 30 systemically-healthy, urban, male patients comprised two groups, based on full mouth periodontal examination: group A patients (n=15) were diagnosed with generalized, severe, chronic periodontitis, and group B patients comprised the control group (n=15), which included patients with a clinically-healthy periodontium. Laboratory blood investigations included hemoglobin (g%), total number of erythrocytes (red blood cells), hematocrit/packed cell volume, erythrocyte sedimentation rate, mean corpuscular volume of erythrocytes, and mean corpuscular hemoglobin concentration. An analysis of covariance using age as a covariate was done to compare the mean values of hematological parameters within groups.', 'The mean values of hemoglobin, red blood cells, packed cell volume, and mean corpuscular hemoglobin concentration were significantly lower, while the mean corpuscular volume of erythrocytes and erythrocyte sedimentation rate were significantly higher in group A patients compared to those in group B, indicating mild anemia.",
            "output": [
                "Is generalized , severe , chronic periodontitis associated with anemia of chronic disease : a pilot study in urban , Indian males?"
            ]
        },
        {
            "id": "task847-29f8a0ca393e4137b5b044577f6ee11e",
            "input": "Increased C-reactive protein levels have been found in all active inflammations, including periodontitis. This study aims to assess the C-reactive protein levels in periodontal disease progression.', 'Forty-five patients were divided into the following three groups (n=15) based on gingival index, probing pocket depth, and clinical attachment level: healthy (group I), gingivitis (group II), and chronic periodontitis (group III). Gingival crevicular fluid and serum samples were quantified for C-reactive protein using enzyme-linked immunosorbent assay.', 'The mean C-reactive protein concentration in gingival crevicular fluid and serum was found to be highest in group III (1233.33ng/mL for gingival crevicular fluid, 5483.33ng/mL for serum), and least in group I (60 ng/mL and 413 ng/mL for gingival crevicular fluid and serum, respectively) The mean C-reactive protein concentration in group II (453.33ng/mL for gingival crevicular fluid and 3565.33 ng/mL for serum) was found to be intermediate.",
            "output": [
                "Does progressive periodontal disease have a simultaneous incremental elevation of gingival crevicular fluid and serum CRP levels?"
            ]
        },
        {
            "id": "task847-b6f3977e1854449a93a8ead5cb66515f",
            "input": "Besides chronic stress, chronic pain is a prevalent determinant for depression. Changes induced in specific brain regions by sustained pain may alter the processing of affective information, thus resulting in anxiodepressive disorders. Here, we compared the role of the anterior cingulate cortex (ACC) and the posterior insular cortex in the anxiodepressive, sensory, and affective aspects of chronic pain.', 'Neuropathic pain was induced by cuffing the right sciatic nerve of C57BL/6J mice. Lesions were performed by local injection of ibotenic acid and chronic activation of the ACC by optogenetic stimulation. Anxiodepressive-related behaviors were evaluated through the novelty suppressed feeding, marble burying, splash, and forced swimming tests. Mechanical thresholds were determined using von Frey filaments, and the relief of spontaneous pain was determined by using place conditioning.', 'The ACC lesion prevented the anxiodepressive consequences of chronic pain without affecting the sensory mechanical allodynia. Conversely, the tonic or spontaneous pain and the anxiodepressive consequences of pain remained present after posterior insular cortex lesion, even though the mechanical allodynia was suppressed. Furthermore, optogenetic stimulation of the ACC was sufficient to induce anxiety and depressive-like behaviors in na\u00efve animals.",
            "output": [
                "Is the anterior cingulate cortex a critical hub for pain-induced depression?"
            ]
        },
        {
            "id": "task847-f29121fa2c2c4bbf80438ea56960da08",
            "input": "Glucagon like peptide-1 (GLP-1), an incretin hormone, regulates glucose metabolism by inducing insulin secretion and suppressing glucagon secretion. The aim of the study is to assess the levels of fasting and post-prandial GLP-1 and their risk for T2DM. A case control study was conducted at the diabetes clinic Sanglah Hospital Denpasar Bali, involving 40 subjects who were native Indonesian citizens and 18-70 years of age. Twenty subjects were allocated as the case group (subjects with T2DM) and 20 subjects were allocated as the control group (subjects with normal glucose tolerance [NGT]). Both fasting intact GLP-1 (FGLP-1) and 60\\xa0minutes post-75 gram glucose loading intact GLP-1 (1hGLP-1) levels were measured.', 'Both fasting and post-prandial GLP-1 levels were significantly lower in subjects with T2DM than those with NGT (2.06\\u2009\u00b1\\u20090.43 vs. 2.87\\u2009\u00b1\\u20090.67\\xa0pg/L, p\\u2009<\\u20090.01; and 2.49\\u2009\u00b1\\u20090.60 vs. 3.42\\u2009\u00b1\\u20090.85\\xa0pg/L, p\\u2009=\\u20090.02; respectively). Low levels of FGLP-1 (OR, 13.5; p\\u2009=\\u20090.001) and 1hGLP-1 (OR, 5.667, p\\u2009=\\u20090.018), with no response after glucose loading (\u2206GLP-1), were a significant risk for T2DM. According to the \u2206GLP-1, there was a tendency of decreasing response of GLP-1 after glucose loading among subjects with T2DM (\u2206\\u2009=\\u20090.43\\xa0pg/L) compared to subjects with NGT (\u2206\\u2009=\\u20090.55\\xa0pg/L).",
            "output": [
                "Is the low level of glucagon-like peptide-1 ( glp-1 ) a risk factor of type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-b7b71c8f68e24b99b512424a6280806d",
            "input": "This study was designed to investigate the hepatoprotective effect of an extract from Shinzami, a variety of purple sweet potato, in rats injured by hepatic ischaemia-reperfusion (I/R).', 'Pretreatment with Shinzami extract decreased the aspirate aminotransferase and alanine aminotransferase serum levels in our hepatic I/R rat model. The glutathione level and superoxide dismutase activity level were significantly higher in the rats pretreated with the Shinzami extract compared with the hepatic I/R rats, and the glutathione peroxidase activity level was higher in pretreated rats. The total anthocyanins extracted from Shinzami, however, only increased the superoxide dismutase activity level in the hepatic I/R rats. Rats pretreated with the Shinzami extract or anthocyanins demonstrated attenuated hepatic pathological changes, such as hepatic distortion, haemorrhage, necrosis and inflammatory cell infiltration compared with the hepatic I/R control rats.",
            "output": [
                "Does shinzami Korean purple-fleshed sweet potato extract prevent ischaemia-reperfusion-induced liver damage in rats?"
            ]
        },
        {
            "id": "task847-2269059de68f40e4b5daa40942bf1ba1",
            "input": "Depression is the most common psychiatric comorbidity in epilepsy patients. The lack of success with current pharmacological interventions for this patient population, highlights the importance of optimizing non-pharmacological neuromodulatory treatments such as vagus nerve stimulation (VNS). Studies on the antidepressant effect of VNS in epilepsy patients may be confounded by concurrent anti-epileptic drug therapy. To date, studies in epilepsy models overcoming this problem are lacking.', 'We investigated whether VNS affects anhedonia, a key symptom of major depression, in the kainic acid rat model for temporal lobe epilepsy.', 'Anhedonia was assessed in kainic acid (KA) and saline (SAL) injected rats using the saccharin preference test (SPT). To exclude differences in taste perception, the quinine aversion test (QAT) was performed. Both groups were randomly subdivided in a VNS and a SHAM group, yielding 4 experimental arms: KA-VNS, KA-SHAM, SAL-VNS and SAL-SHAM. Both VNS groups received 2 weeks of VNS, while the SHAM groups were not stimulated. Thereafter, the SPT and QAT were repeated.', 'Saccharin preference was significantly reduced in the KA compared to the SAL rats (P\\xa0<\\xa00.05), without differences in quinine aversion. Two weeks of VNS significantly increased the saccharin preference in the KA-VNS group (P\\xa0<\\xa00.05), while it had no effect on quinine aversion. No effects of VNS or SHAM were found in the other groups.",
            "output": [
                "Does vagus nerve stimulation have antidepressant effects in the kainic acid model for temporal lobe epilepsy?"
            ]
        },
        {
            "id": "task847-59f064703f3d436c94fa2c356608f625",
            "input": "To determine the frequency and clinical significance of epidermal growth factor receptor (EGFR) mutations in patients with potentially curable stage III non-small-cell lung cancer (NSCLC) who are eligible for definitive chemoradiotherapy (CRT).', 'Between January 2001 and December 2010, we analyzed the EGFR mutational status in consecutive NSCLC patients who were treated by CRT. The response rate, relapse-free survival, 2-year relapse-free rate, initial relapse sites, and overall survival of the patients were investigated.', 'A total of 528 patients received CRT at our hospital during the study period. Of these, 274 were diagnosed as having nonsquamous NSCLC. Sufficient specimens for mutational analyses could be obtained from 198 of these patients. The proportion of patients with EGFR activating mutations was 17%. In addition to the well-known characteristics of patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller primary lesions (T1/2) was found to be higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with EGFR mutations showed similar response rate, relapse-free survival, and 2-year relapse-free rates as compared to patients with wild-type EGFR. Local relapses as the site of initial relapse occurred significantly less frequently in patients with EGFR mutation (4% vs 21%; P=.045). Patients with EGFR mutations showed longer local control (adjusted hazard ratio 0.49; P=.043). After disease progression, a majority of the patients with EGFR mutations received EGFR tyrosine kinase inhibitors (62%), and these patients showed longer postprogression survival than those with wild-type EGFR.",
            "output": [
                "Is epidermal growth factor receptor mutation associated with longer local control after definitive chemoradiotherapy in patients with stage III nonsquamous non-small-cell lung cancer?"
            ]
        },
        {
            "id": "task847-4d47ee3190bb49798e890baa29f4a3a5",
            "input": "ST22-IV is a successful hospital-associated MRSA clone. Due to its known ability to replace other MRSA clones in hospitals, it became a dominant clone in Europe and beyond. So far, there are no studies investigating the relationship between the epidemiological success of MRSA clones and their capacity to withstand commonly encountered stresses.', 'We investigated the fitness of ST22-IV in comparison with the replaced clone ST228-I, evaluating its resistance to oxidative stress, autolytic activity, growth at high osmolarity and in acid and alkaline environments and survival under desiccation and heat shock. We also compared their phenotypic characteristics and examined the impact of antibiotic consumption on epidemiological success.', 'Here we demonstrate that the dominance of ST22-IV is linked neither to changes in antibiotic consumption nor to acquisition of additional resistances over time. Strong \u03b1-haemolysin activity, the production of \u03b2-haemolysin and the presence of an active agr could partly explain the virulence of ST22-IV previously observed in a murine model of pneumonia. Most importantly, we show that ST22-IV compared with ST228-I, besides retaining susceptibility to most antibiotics over time, has a superior capacity to survive under all stress conditions tested, which bacteria commonly face during their life cycle.",
            "output": [
                "Is epidemic MRSA clone ST22-IV more resistant to multiple host- and environment-related stresses compared with ST228-I?"
            ]
        },
        {
            "id": "task847-5ea802796bf5473ea6ceedd51eb5d24c",
            "input": "The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon.', 'In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (\u22651000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls.', 'At Month 12, 38/238 (16%) patients experienced virological failure (\u22651000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n\\u200a=\\u200a18) and K103N (n\\u200a=\\u200a10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P\\u200a=\\u200a0.77). Lower CD4 count at baseline (OR per 100 cells/mm(3) lower 1.41, 95% CI 1.02-1.96, P\\u200a=\\u200a0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P\\u200a<\\u200a0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence.",
            "output": [
                "Is virological failure after 1 year of first-line ART associated with HIV minority drug resistance in rural Cameroon?"
            ]
        },
        {
            "id": "task847-f96c03008abb4e7bb9e41f3718853382",
            "input": "Previous reports have indicated an association between blood transfusion and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. However, clinicopathological biases were not adjusted in these studies. We aimed to clarify the effect of blood transfusions in patients with HCC and Child-Pugh class A after hepatectomy by using inverse probability of treatment weighting (IPTW) analysis for selection bias control.', 'We enrolled 479 patients with primary HCC and Child-Pugh class A retrospectively (91 transfused and 388 nontransfused patients) who underwent curative hepatectomy. After adjusting for different covariate distributions for both groups by IPTW, we analyzed the prognostic outcomes.', 'In the unweighted analyses, overall survival (OS) rate of transfused patients was significantly lower than in nontransfused patients (P < 0.0001). Recurrence-free survival (RFS) rate of transfused patients was significantly lower than that of nontransfused patients (P = 0.0024). Multivariate analysis showed that blood transfusion was an independent prognostic factor of OS and RFS. The different distributive covariates between the two groups were age, presence of liver cirrhosis, serum level of alpha-fetoprotein, maximum tumor diameter, and amount of intraoperative blood loss. After IPTW by these covariates, OS rate of transfused patients was not significantly lower than those of nontransfused patients, whereas RFS rate of transfused patients remained significantly lower than those of nontransfused patients (P = 0.038, adjusted HR 1.45; 95% CI 1.0-2.1).",
            "output": [
                "Is blood transfusion associated with recurrence of hepatocellular carcinoma after hepatectomy in Child-Pugh class A patients?"
            ]
        },
        {
            "id": "task847-4432c3e4cd26451face084ab8898e477",
            "input": "To evaluate the superiority of transcutaneous oxygen pressure (TcPO2) before, during and after peripheral transluminal angioplasty (PTA) in comparison with ankle brachial index (ABI) in patients with diabetes.', '40 consecutive patients with diabetes treated by PTA where included. This study shows results before, during and after PTA and their progression for 8 weeks.', 'The TcPO2 increased from 28.11\\u2009\u00b1\\u20098.1 to 48.03\\u2009\u00b1\\u20098.4\\u2009mmHg, 8 weeks after PTA (p\\u2009<\\u20090.001). The ABI increased from 0.48\\u2009\u00b1\\u20090.38 to 0.77\\u2009\u00b1\\u20090.39 after PTA (p\\u2009<\\u20090.001). After PTA, the stenosis of the vessel decreased from 58.33\\u2009\u00b1\\u200920.07% to 21.87\\u2009\u00b1\\u200913.57% (p\\u2009<\\u20090.001). TcPO2 was determined in all the patients, but ABI could not be determined in all patients. Furthermore, we determined patients with \"false negatives\" with an improvement in ABI and \"false positives\" in 12.5% of patients. Additionally, in this study, we monitored TcPO2 while performing PTA, revealing variations in each phase of the radiological procedure.",
            "output": [
                "Does transcutaneous oxygen tension measurements following peripheral transluminal angioplasty procedure have more specificity and sensitivity than ankle brachial index?"
            ]
        },
        {
            "id": "task847-749fbe49945847e0b4f92570a00ff00e",
            "input": "Obesity has become a significant public health concern in the United States. The goal of this study was to assess the effect of obesity on postoperative complications after operative management of proximal humerus fractures by use of a national database.', 'Patients who underwent operative management of a proximal humerus fracture were identified in a national database by Current Procedural Terminology codes for procedures in patients with International Classification of Diseases, Ninth Revision (ICD-9) codes for proximal humerus fracture, including (1) open reduction and internal fixation, (2) intramedullary nailing, (3) hemiarthroplasty, and (4) total shoulder arthroplasty. These groups were then divided into obese and nonobese cohorts by use of ICD-9 codes for obesity, morbid obesity, or body mass index >30. Each cohort was then assessed for local and systemic complications within 90 days and mortality within 2 years postoperatively. Odds ratios and 95% confidence intervals were calculated.', 'From 2005 to 2011, 20,319 patients who underwent operative management of proximal humerus fractures were identified, including 14,833 (73.0%) open reduction and internal fixation, 1368 (9.2%) intramedullary nail, 3391 (16.7%) hemiarthroplasty, and 727 (3.6%) shoulder arthroplasty. Overall, 3794 patients (18.7%) were coded as obese, morbidly obese, or body mass index >30. In each operative group, obesity was associated with a substantial increase in local and systemic complications.",
            "output": [
                "Is obesity associated with increased postoperative complications after operative management of proximal humerus fractures?"
            ]
        },
        {
            "id": "task847-3313d9c21a97404ca7b90ccaf9c012ea",
            "input": "To evaluate the efficacy and safety of radiofrequency (RF) ablation for treatment of bilateral thyroid nodules as well as preservation of thyroid function.', 'Between January 2007 and October 2012, 18 patients (16 women and 2 men; mean age, 49.9 y; median age, 44 y; age range, 27-81 y) with bilateral thyroid nodules treated by RF ablation were included in this study. The inclusion criteria included bilateral thyroid nodules, pressure symptoms or cosmetic problems, cytologic confirmation of benignancy without atypical cells, and patient refusal of surgery. We used an RF generator (Cool-tip RF system [Covidien, Boulder, Colorado] or SSP-2000, Taewoong Medical Co, Ltd [Gyeonggi-do, Republic of Korea]) and an 18-gauge internally cooled electrode with 1-cm active tips (Cool-tip [Covidien] or Well-Point RF electrode [Taewoong Medical Co, Ltd]). RF ablation was conducted using the moving shot technique and a trans-isthmic approach. RF ablation was performed in separate sessions for nodules in each lobe. Follow-up ultrasound examinations were performed at 1-6 months, 6-12 months, and during the last month of follow-up. The diameter and volume of the nodule and clinical problems including cosmetic and symptom scores were evaluated before and after the procedure.', 'The mean initial nodule size was 4.1 cm \u00b1 1.9, although there was a significant decrease by the time of the last follow-up examination (range, 1-48 mo; mean, 18.1 mo \u00b1 12.8; P < .001, 2.5 cm \u00b1 1.4). The initial nodule volume was 24.4 mL \u00b1 32.2 and was decreased at the last follow-up (6.3 mL \u00b1 19.0, P < .001), with a mean volume reduction of 75.9% \u00b1 19.0. The symptom (P < .001) and cosmetic (P < .001) scores were decreased. Serum hormone levels did not differ significantly before treatment and at the last follow-up (P > .05).",
            "output": [
                "Is radiofrequency ablation a thyroid function-preserving treatment for patients with bilateral benign thyroid nodules?"
            ]
        },
        {
            "id": "task847-910dd3754f8241c4b93e7b44e4dd1b25",
            "input": "Multiple myeloma (MM) is an incurable B-cell cancer with accumulated clonal abnormal plasma cells in bone marrow of patients. MCL-1 (myeloid cell leukemia sequence 1) protein is an anti-apoptotic molecule in MM cells and regulated by pro-inflammatory cytokine IL-6 and downstream signaling molecules STAT3, PI3K and MAPK. The purpose of this study is to investigate the effect of STAT3, PI3K and MAPK gene silence on MCL-1 expression in human MM cells and the consequence of cell survival.', 'Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down STAT3, PI3K or MAPK genes. Gene and protein expression was quantified by quantitative real-time PCR and Western Blot. MM cell apoptosis was examined by annexin-V FITC/propidium iodide staining.', 'Efficient silence of STAT3, PI3K, MAPK1 or MAPK2 gene robustly abrogated IL-6 enhanced MCL-1 expression and suppressed MM cell growth. Silencing STAT3 gene inhibited PI3K expression, silencing PI3K markedly abrogated STAT3 and MAPK production. Inhibition of MAPK2 gene by shMAPK2 suppressed STAT3, PI3K and MAPK1 expression in the cells. Silencing of STAT3, PI3K and MAPK2 together completely blocked MCL-1 expression in MM cells.",
            "output": [
                "Does silence of MCL-1 upstream signaling by shRNA abrogate multiple myeloma growth?"
            ]
        },
        {
            "id": "task847-cd95f90606714d11a9d3a30861b11f1d",
            "input": "To examine the effect of time after birth on heart rate (HR) measured by pulse oximetry (PO) (HRPO) and electrocardiography (ECG) (HRECG).', 'HRECG and HRPO (collected at maximum sensitivity) were assessed in 53 term and preterm infants at birth. ECG electrodes and a PO sensor were attached as soon as possible and HRECG and HRPO were compared every 30 seconds from 1-10 minutes after birth. Data were compared using a Wilkinson signed-rank test. Clinical relevance (eg, HR <100 beats per minute [bpm] was tested using a McNemar test).', 'Seven hundred fifty-five data pairs were analyzed. Median (IQR) gestational age was 37 (31-39) weeks. Mean (SD) starting time of PO and ECG data collection was 99 (33) vs 82 (26) seconds after birth (P = .001). In the first 2 minutes after birth, HRPO was significantly lower compared with HRECG (94 (67-144) vs 150 (91-153) bpm at 60 seconds (P < .05), 81 (60-109) vs 148 (83-170) bpm at 90 seconds (P < .001) and 83 (67-145) vs 158 (119-176) at 120 seconds (P < .001). A HR <100 bpm was more frequently observed with a PO than ECG in the first 2 minutes (64% vs 27% at 60 seconds (P = .05), 56% vs 26% at 90 seconds (P < .05) and 53% vs 21% at 120 seconds (P < .05). HR by ECG was verified by ultrasound for outflow from a subset of infants.",
            "output": [
                "Does pulse oximetry measure a lower heart rate at birth compared with electrocardiography?"
            ]
        },
        {
            "id": "task847-04fed303019c40d7bb5d3bc3a087d1b8",
            "input": "Brivaracetam (BRV) is an antiepileptic drug in Phase III clinical development. BRV binds to synaptic vesicle 2A (SV2A) protein and is also suggested to inhibit voltage-gated sodium channels (VGSCs). To evaluate whether the effect of BRV on VGSCs represents a relevant mechanism participating in its antiepileptic properties, we explored the pharmacology of BRV on VGSCs in different cell systems and tested its efficacy at reducing the sustained repetitive firing (SRF).', 'Brivaracetam investigations on the voltage-gated sodium current (I(Na)) were performed in N1E-155 neuroblastoma cells, cultured rat cortical neurons, and adult mouse CA1 neurons. SRF was measured in cultured cortical neurons and in CA1 neurons. All BRV (100-300 \u03bcM) experiments were performed in comparison with 100 \u03bcM carbamazepine (CBZ).', 'Brivaracetam and CBZ reduced IN a in N1E-115 cells (30% and 40%, respectively) and primary cortical neurons (21% and 47%, respectively) by modulating the fast-inactivated state of VGSCs. BRV, in contrast to CBZ, did not affect I(Na) in CA1 neurons and SRF in cortical and CA1 neurons. CBZ consistently inhibited neuronal SRF by 75-93%.",
            "output": [
                "Does brivaracetam differentially affect voltage-gated sodium currents without impairing sustained repetitive firing in neurons?"
            ]
        },
        {
            "id": "task847-3c9420a4d38d4a64b5ee57cc0ce00105",
            "input": "The long lasting behavioural and cognitive impairments in offspring prenatally exposed to nicotine have been confirmed in animal models. In the present study, we investigated the effect of ascorbic acid on prenatal nicotine exposure induced behavioral deficits in male offspring of rats.', 'The pregnant Wistar dams were divided into four groups of six rats: control, vehicle control, nicotine and nicotine+ascorbic acid groups. The nicotine group received daily dose of subcutaneous injections of 0.96 mg/kg body weight (bw) nicotine free base throughout gestation. Pregnant dams in nicotine+ascorbic acid group were first given nicotine free base (0.96 mg/kg bw/day; subcutaneous route) followed by ascorbic acid (50 mg/kg bw/day, orally) daily throughout gestation. The cognitive function of male offspring of all the experimental groups was studied using Morris water maze test at postnatal day 40.', 'Prenatal nicotine exposure altered spatial learning and memory in male offspring. However, treatment with ascorbic acid ameliorated these changes in rats.",
            "output": [
                "Does ascorbic Acid ameliorate nicotine exposure induced impaired spatial memory performances in rats?"
            ]
        },
        {
            "id": "task847-30f8dcc4c1a843bfa20e0ce145431d6b",
            "input": "The aim of this study was to investigate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) gene polymorphisms contributed to development of gestational diabetes mellitus (GDM).', 'Fifty women with diagnosis of GDM and 50 control individuals without GDM or altered glucose intolerance during their pregnancy were enrolled in the study. Multiplex polimerase chain reaction-restriction fragment length polymorphism method was applied to determine the GSTM1 and GSTT1 gene polymorphisms. Genotypes were determined according to bands detected with the agarose gel electrophoresis.', 'The difference in the frequencies of GSTM1 null genotypes between GDM and control groups was not statistically significant (60% and 54%, respectively). There was no statistically significant difference between GDM and control groups with respect to GSTT1 null genotype rates (22% and 20%, respectively).There was no statistically significant difference between GDM and control groups with respect to GSTT1 null genotype rates (22% and 20%, respectively).",
            "output": [
                "Are glutathione s-transferase m1 and t1 gene polymorphisms associated with increased risk of gestational diabetes mellitus development?"
            ]
        },
        {
            "id": "task847-a676ff65107e40e5aed227de0605d878",
            "input": "To engineer a stable HLA-G molecule and evaluate its immunomodulatory properties in transgenic human dermal fibroblasts (HDFs).', \"A mutated HLA-G1 (mHLA-G1) molecule was generated by modifying the endoplasmic reticulum retrieval motif and 3'-untranslated region miRNA-binding sites of HLA-G1. Immunomodulatory properties of transgenic HDF-mHLA-G1 were evaluated in vitro.\", 'Stable mHLA-G1 expressing HDF cells were successfully generated and flow cytometry analysis revealed that mHLA-G1 efficiently localized to the cell surface. Natural killer cell-mediated cytolysis of HDF-mHLA-G1/green fluorescent protein (GFP) was reduced by 73% compared with HDF-GDP. HDF-mHLA-G1/GFP decreased phytohemagglutinin-activated peripheral blood mononuclear cell proliferation by 30% versus HDF-GFP.",
            "output": [
                "Does heterologous expression of mutated HLA-G1 reduce alloreactivity of human dermal fibroblasts?"
            ]
        },
        {
            "id": "task847-df8b699580404801a8c9942a5cf053da",
            "input": "Childhood asthma morbidity remains significant, especially in low-income children. Most often, asthma management is provided by the child's primary care provider.\", 'We sought to evaluate whether enhancing primary care management for persistent asthma with telephone-based peer coaching for parents reduced asthma impairment and risk in children 3 to 12 years old.', 'Over 12 months, peer trainers provided parents with asthma management training by telephone (median, 18 calls) and encouraged physician partnership. The intervention was evaluated in a cluster-randomized trial of 11 intervention and 11 usual care pediatric practices (462 and 486 families, respectively). Patient outcomes were assessed by means of telephone interviews at 12 and 24 months conducted by observers blinded to intervention assignment and compared by using mixed-effects models, controlling for baseline values and clustering within practices. In a planned subgroup analysis we examined the heterogeneity of the intervention effect by insurance type (Medicaid vs other).', 'After 12 months, intervention participation resulted in 20.9 (95% CI, 9.1-32.7) more symptom-free days per child than in the control group, and there was no difference in emergency department (ED) visits. After 24 months, ED visits were reduced (difference in mean visits/child, -0.28; 95% CI, -0.5 to -0.02), indicating a delayed intervention effect. In the Medicaid subgroup, after 12 months, intervention participation resulted in 42% fewer ED visits (difference in mean visits/child, -0.50; 95% CI, -0.81 to -0.18) and 62% fewer hospitalizations (difference in mean hospitalizations/child, -0.16; 95% CI, -0.30 to -0.014). Reductions in health care use endured through 24 months.",
            "output": [
                "Does a cluster-randomized trial show telephone peer coaching for parents reduces children 's asthma morbidity?"
            ]
        },
        {
            "id": "task847-7eb25be588964556b7945e0e29a00fad",
            "input": "Metabolic adaptations are essential during tumour growth to maintain the high proliferation levels exhibited by cancer cells. In this study, we examined the transformations that occurred in the lipid metabolism in astrocytic tumours, and the possible role of the fuel-sensing enzyme AMPK. Metabolic targets might help design new and effective drugs for cancer.', 'To accomplish this objective, we studied both mice and human astrocytic tumours. We first used a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We then confirmed the results in human glioblastoma cell lines and in glioblastoma tissue samples from patients.', \"We show that the high levels of activated AMPK, observed in astrocytic tumours, increase extracellular lipid internalisation and reduce energy expenditure by inhibiting 'de novo' fatty acid (FA) synthesis, which allows tumour cells to obtain building blocks and energy to be able to create new organelles and new cells.",
            "output": [
                "Is lipoprotein internalisation induced by oncogenic AMPK activation essential to maintain glioblastoma cell growth?"
            ]
        },
        {
            "id": "task847-31351048c0f54dccaf775836fad2a5de",
            "input": "To ensure that clinical practice guidelines (CPGs) form a sound basis for decision-making in health care, it is necessary to be able to reliably assess and ensure their quality. This results in the need to assess the content of guidelines systematically, particularly with regard to the validity of their recommendations.The aim of the present analysis was to determine the suitability and applicability of frequently used assessment tools for evidence syntheses with regard to the assessment of guideline content.', 'We conducted a systematic comparison and analysis of established tools for the assessment of evidence syntheses (guidelines, systematic reviews, health technology assessments). The tools analyzed were: ADAPTE, AGREE II, AMSTAR, GLIA and the INAHTA checklist. We analyzed methodological steps related to the assessment of the reliability and validity of guideline recommendations. Data were extracted and analyzed by two persons independently of one another.', 'Widely used tools for the methodological assessment of evidence syntheses are not suitable for a comprehensive content-related assessment. They remain mostly at the level of assessment of the documentation of processes. Some tools assess selected content-related aspects, but operationalization is either unspecific or lacking.",
            "output": [
                "Are tools for assessing the content of guidelines needed to enable their effective use -- a systematic comparison?"
            ]
        },
        {
            "id": "task847-9db4f2e033be48e4b3426b55cc3654d2",
            "input": "Exacerbation-associated uncontrolled asthma represents a major public health problem. The relationship of elevated blood eosinophils to this process needs study.', 'To determine whether a high blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma.', 'By using electronic pharmacy and health care data from Kaiser Permanente Southern California, 2392 patients, ages 18 to 64 years, were identified who met the Health Effectiveness Data and Information Set 2-year criteria for persistent asthma, did not manifest chronic obstructive pulmonary disease and other major illnesses, and had a blood eosinophil determination in 2010. Exacerbations (primary outcome) were defined as asthma outpatient visits that required systemic corticosteroid dispensing within \u00b17 days or asthma emergency department visits or hospitalizations. A period of \u22658 days defined a new exacerbation. Multivariate modelling used negative binomial and Poisson regression to examine the association between a blood eosinophil count determined in 2010 and risk of exacerbations, and \u22657 short-acting \u03b22-agonist (SABA) canisters dispensed (secondary outcome) in 2011 by adjusting for demographics, comorbidities, and asthma burden.', 'The rate of asthma exacerbations in 2011 was 0.41 events per person year (95% CI, 0.37-0.45). Eosinophil count \u2265400/mm(3) in 2010 was a risk factor for asthma exacerbations in 2011 (adjusted rate ratio 1.31 [95% CI, 1.07-1.60]; P = .009) and \u22657 SABA dispensed (adjusted risk ratio 1.17 [95% CI, 1.03-1.1.33]; P = .015).",
            "output": [
                "Is high blood eosinophil count a risk factor for future asthma exacerbations in adult persistent asthma?"
            ]
        },
        {
            "id": "task847-1aa184622830417db6cfabd643afaae2",
            "input": "Benefits to crop productivity arising from increasing CO2 fertilization may be offset by detrimental effects of global climate change, such as an increasing frequency of drought. Phosphorus (P) nutrition plays an important role in crop responses to water stress, but how elevated CO2 (eCO2) and P nutrition interact, especially in legumes, is unclear. This study aimed to elucidate whether P supply improves plant drought tolerance under eCO2.', 'A soil-column experiment was conducted in a free air CO2 enrichment (SoilFACE) system. Field pea (Pisum sativum) was grown in a P-deficient vertisol, supplied with 15 mg P kg(-1) (deficient) or 60 mg P kg(-1) (adequate for crop growth) and exposed to ambient CO2 (aCO2; 380-400 ppm) or eCO2 (550-580 ppm). Drought treatments commenced at flowering. Measurements were taken of soil and leaf water content, photosynthesis, stomatal conductance, total soluble sugars and inorganic P content (Pi).', 'Water-use efficiency was greatest under eCO2 when the plants were supplied with adequate P compared with other treatments irrespective of drought treatment. Elevated CO2 decreased stomatal conductance and transpiration rate, and increased the concentration of soluble sugars and relative water contents in leaves. Adequate P supply increased concentrations of soluble sugars and Pi in drought-stressed plants. Adequate P supply but not eCO2 increased root length distribution in deeper soil layers.",
            "output": [
                "Do phosphorus application and elevated CO2 enhance drought tolerance in field pea grown in a phosphorus-deficient vertisol?"
            ]
        },
        {
            "id": "task847-01bce2c9c167426b98e3964cda56b968",
            "input": "Parents take an important role in a child's development, but there is currently limited information on parental correlates with children's health behaviour. The purpose of this study, therefore, was to examine whether parental characteristics, such as body weight, TV consumption and sport participation, affect children's body weight and health behaviour.\", \"To examine the effects of parental characteristics on children's body weight and health behaviour, baseline data of 1,118 elementary school children (7.6 \u00b1 0.4 years) participating in a school-based intervention in southwest Germany was used. Children's height and weight were measured and parent as well as child behaviour was assessed via questionnaire.\", 'BMI percentiles of children were positively associated with parental BMI (r = 0.2, p <0.01). Further, high parental TV time increased the odds for high TV time in children (OR mother= 2.2, OR father = 2.3) and parental club sport participation increased the odds for club sport participation in children (OR mother = 1.9, OR father = 1.7). The relationship between parental and child behaviour was stronger than the relationship between parental BMI and BMI percentiles of the child.",
            "output": [
                "Do parental characteristics have a larger effect on children 's health behaviour than their body weight?"
            ]
        },
        {
            "id": "task847-183bd0eb73bc46a9869028c88adbbdde",
            "input": "Certain circulating cells have been shown to predict the clinical outcome of several cancers. The objective of this study was to identify clinical, hematological and immunological predictors of prognosis in non-small cell lung cancer (NSCLC) patients.', 'A retrospective study on a prevalent cohort of 225 NSCLC patients hospitalized at the Zhejiang Province Cancer Hospital (ZPCH) was conducted from August 1, 2006 to April 15, 2008. Circulating lymphocytes were measured by flow cytometry. WBC count and classification in peripheral blood were measured with a Coulter counter. We calculated the proportion of patients surviving after first hospital admission and hazard ratios (HR) using the Cox proportional hazards model.', 'Elevated levels of preoperative circulating CD44(+) lymphocytes, WBCs and neutrophils indicated low cumulative survival. Clinical stage (HR: 2.292; 95% confidence interval (CI): 1.34-3.91, P=0.002), neutrophils (HR: 1.877; 95% CI: 1.34-2.62, P<0.001) and CD44(+) lymphocytes (HR: 1.018; 95% CI: 1.00-1.03, P=0.002) are independent predictors of survival in NSCLC patients, respectively. Elevated levels of CD44(+) lymphocytes and neutrophils correlated with distant metastasis and prognosis in NSCLC patients with stage III/IV, respectively.",
            "output": [
                "Do elevated levels of preoperative circulating CD44\u207a lymphocytes and neutrophils predict poor survival for non-small cell lung cancer patients?"
            ]
        },
        {
            "id": "task847-4e6358d5011b4607b4c96870ae6f57d1",
            "input": "Membrane-associated guanylate kinase (MAGUK) proteins are important determinants of ion channel organization in the plasma membrane. In the heart, the MAGUK protein SAP97, encoded by the DLG1 gene, interacts with several ion channels via their PDZ domain-binding motif and regulates their function and localization.', 'The purpose of this study was to assess in vivo the role of SAP97 in the heart by generating a genetically modified mouse model in which SAP97 is suppressed exclusively in cardiomyocytes.', 'SAP97(fl/fl) mice were generated by inserting loxP sequences flanking exons 1-3 of the SAP97 gene. SAP97(fl/fl) mice were crossed with \u03b1MHC-Cre mice to generate \u03b1MHC-Cre/SAP97(fl/fl) mice, thus resulting in a cardiomyocyte-specific deletion of SAP97. Quantitative reverse transcriptase-polymerase chain reaction, western blots, and immunostaining were performed to measure mRNA and protein expression levels, and ion channel localization. The patch-clamp technique was used to record ion currents and action potentials. Echocardiography and surface ECGs were performed on anesthetized mice.', 'Action potential duration was greatly prolonged in \u03b1MHC-Cre/SAP97(fl/fl) cardiomyocytes compared to SAP97(fl/fl) controls, but maximal upstroke velocity was unchanged. This was consistent with the decreases observed in IK1, Ito, and IKur potassium currents and the absence of effect on the sodium current INa. Surface ECG revealed an increased corrected QT interval in \u03b1MHC-Cre/SAP97(fl/fl) mice.",
            "output": [
                "Does cardiac-specific ablation of synapse-associated protein SAP97 in mice decrease potassium currents but not sodium current?"
            ]
        },
        {
            "id": "task847-7afc303498774f53a977f1dbcb77d4bb",
            "input": "A prominent feature of many human cancers is oncogene-driven activation of the DNA damage response (DDR) during early tumorigenesis. It has been shown previously that noninvasive imaging of the phosphorylated histone H2A variant H2AX, \u03b3H2AX, a DNA damage signaling protein, is possible using (111)In-labeled anti-\u03b3H2AX antibody conjugated to the cell-penetrating peptide transactivator of transcription (TAT). The purpose of this study was to investigate whether (111)In-anti-\u03b3H2AX-TAT detects the DDR during mammary oncogenesis in BALB-neuT mice.', 'Mammary fat pads from BALB-neuT and wild-type mice (age, 40-106 d) were immunostained for \u03b3H2AX. (111)In-anti-\u03b3H2AX-TAT or a control probe was administered intravenously to BALB-neuT mice. SPECT was performed weekly and compared with tumor detection using palpation and dynamic contrast-enhanced MR imaging.', '\u03b3H2AX expression was elevated in hyperplastic lesions in the mammary fat pads of BALB-neuT mice aged 76-106 d, compared with normal fat pads from younger mice and carcinomas from older mice (13.5 \u00b1 1.2 \u03b3H2AX foci/cell vs. 5.2 \u00b1 1.5 [P < 0.05] and 3.4 \u00b1 1.1 [P < 0.001], respectively). Serial SPECT imaging revealed a 2.5-fold increase in (111)In-anti-\u03b3H2AX-TAT accumulation in the mammary fat pads of mice aged 76-106 d, compared with control probe (P = 0.01). The median time to detection of neoplastic lesions by (111)In-anti-\u03b3H2AX-TAT (defined as >5% injected dose per gram of tissue) was 96 d, compared with 120 and 131 d for dynamic contrast-enhanced MR imaging and palpation, respectively (P < 0.001).",
            "output": [
                "Does imaging DNA damage allow detection of preneoplasia in the BALB-neuT model of breast cancer?"
            ]
        },
        {
            "id": "task847-26a04cc487e34ad9aa49260ec28dedaf",
            "input": "Accumulation and infiltration of microglia/brain macrophages around and into glioma tissue promote tumor invasion and expansion. One tumor-promoting mechanism of microglia/brain macrophages is upregulation of membrane type 1 matrix metalloprotease (MT1-MMP), which promotes the degradation of extracellular matrix. MT1-MMP upregulation is induced by soluble factors released by glioma cells activating microglial Toll-like receptor 2 (TLR2).', 'Versican identified by proteomics was silenced in glioma cells by short interference RNA and short hairpin RNA approaches and studied in vitro and after injection into mouse brains or organotypic brain slices.', 'The splice variants V0/V1 of the endogenous TLR2 ligand versican are highly expressed in mouse and human glioma tissue. Versican-silenced gliomas induced less MT1-MMP expression in microglia both in vitro and in vivo, which resulted in smaller tumors and longer survival rates as compared with controls. Recombinant versican V1 induced significantly higher levels of MT1-MMP in wild-type microglia compared with untreated and treated TLR2 knockout microglial cells. Using glioma-injected organotypic brain slices, we found that the impact of versican signaling on glioma growth depended on the presence of microglia. Moreover, we found that TLR2 expression is upregulated in glioma-associated microglia but not in astrocytes. Additionally, an established TLR2 neutralizing antibody reduced glioma-induced microglial MT1-MMP expression as well as glioma growth ex vivo.",
            "output": [
                "Does glioma-derived versican promote tumor expansion via glioma-associated microglial/macrophages Toll-like receptor 2 signaling?"
            ]
        },
        {
            "id": "task847-e4d18bc7ad22482c9add7dd99fe571b3",
            "input": "This study compared in-hospital mortality and resource utilization among vascular surgical patients at safety net public hospitals (SNPHs) with those at nonsafety net public hospitals (nSNPHs).', 'The National Inpatient Sample (2003-2011) was queried to identify surgical patients with peripheral arterial disease (PAD), carotid stenosis, or nonruptured abdominal aorta aneurysm based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and procedure codes. The cohort was then divided into SNPH and nSNPH groups according to the definition of SNPH used by the National Association of Public Hospitals. Clinical characteristics, length of stay, in-hospital mortality, and hospital charges were compared between groups. Advanced PAD was defined as that associated with rest pain or tissue loss. Statistical methods included bivariate \u03c7(2) tests for categoric variables, t-tests for continuous variables, and multivariable linear and logistic regression to adjust for confounding variables (in-hospital mortality).', 'We identified 306,438 patients operated on for PAD, carotid stenosis, and abdominal aortic aneurysm. Patients at SNPHs were younger, the percentage of female and minority patients was higher, and patients had a higher Elixhauser comorbidity index (P < .001). Nonelective admissions were more common among SNPH patients who presented with more advanced PAD (P > .05) and symptomatic carotid stenosis (P < .05). Patients at SNPHs had a significantly longer length of stay, higher hospital charges, and higher in-hospital mortality (P < .05 for all variables). Crude odds of mortality at SNPHs were 1.28 higher than at nSNPHs (95% confidence interval, 1.13-1.46; P < .001), but adjusted analyses revealed no statistically significant difference between the odds of in-hospital mortality at both hospital groups.",
            "output": [
                "Is care of patients undergoing vascular surgery at safety net public hospitals associated with higher cost but similar mortality to nonsafety net hospitals?"
            ]
        },
        {
            "id": "task847-7ecff681324944c4a751f6a68eb7a8a1",
            "input": "Bariatric surgery is associated with cognitive benefits, but the nature of such gains may be variable across demographically and clinically diverse persons. Older adults achieve less weight loss and resolution of fewer medical co-morbidities after surgery compared to younger patients and are also at heightened risk for nutritional deficiencies. However, no study has examined the influence of age on cognitive improvements after bariatric surgery. The objective of this study was to determine the effects of age on cognitive function postbariatric surgery.', 'A total of 95 participants enrolled in the Longitudinal Assessment for Bariatric Surgery completed a computerized cognitive test battery before bariatric surgery and at 12-weeks and 12-months postoperatively.', 'Baseline cognitive impairments were common. Significant improvements were found in attention/executive function and memory abilities 12-weeks and 12-months after surgery. Age was not associated with baseline cognitive test performance. Separate multivariable regression analyses controlling for baseline attention/executive function and memory also showed that age was not a significant predictor of 12-week or 12-month performances in these domains (P>.05 for all).",
            "output": [
                "Does older age limit postbariatric surgery cognitive benefits : a preliminary investigation?"
            ]
        },
        {
            "id": "task847-94f8ef157d9f47f9a42687e8c5af3b7e",
            "input": "To study the association between self-reported sleep disturbances and dementia risk.', 'Self-reported sleep disturbances and established risk factors for dementia were measured in men at ages 50 (n\\xa0=\\xa01574) and 70 (n\\xa0=\\xa01029) years. Dementia incidence was determined by reviewing their patient history between ages 50 and 90 years. In addition, plasma levels of \u03b2-amyloid (A\u03b2) peptides 1-40 and 1-42 were measured at ages 70, 77, and 82 years.', \"Cox regression demonstrated that men with self-reported sleep disturbances had a higher risk of developing dementia (+33%) and Alzheimer's disease (AD, +51%) than men without self-reported sleep disturbances (both P\\xa0<\\xa0.05). Binary logistic regression showed the increased risk for both dementia (+114%) and AD (+192%) were highest when sleep disturbance was reported at age 70 years (both P\\xa0<\\xa0.001). No group differences were found in A\u03b2 levels.",
            "output": [
                "Is self-reported sleep disturbance associated with Alzheimer 's disease risk in men?"
            ]
        },
        {
            "id": "task847-b2ce55b28a204dd792492b1436f7b7e3",
            "input": "Animals control the speed of motion to meet behavioral demands. Yet, the underlying neuronal mechanisms remain poorly understood. Here we show that a class of segmentally arrayed local interneurons (period-positive median segmental interneurons, or PMSIs) regulates the speed of peristaltic locomotion in Drosophila larvae.', 'PMSIs formed glutamatergic synapses on motor neurons and, when optogenetically activated, inhibited motor activity, indicating that they are inhibitory premotor interneurons. Calcium imaging showed that PMSIs are rhythmically active during peristalsis with a short time delay in relation to motor neurons. Optogenetic silencing of these neurons elongated the duration of motor bursting and greatly reduced the speed of larval locomotion.",
            "output": [
                "Does a group of segmental premotor interneurons regulate the speed of axial locomotion in Drosophila larvae?"
            ]
        },
        {
            "id": "task847-90ead618a24e45b292d438e394245ee1",
            "input": "Plant body plans arise by the activity of meristematic growing tips during development and radiated independently in the gametophyte (n) and sporophyte (2n) stages of the life cycle during evolution. Although auxin and its intercellular transport by PIN family efflux carriers are primary regulators of sporophytic shoot development in flowering plants, the extent of conservation in PIN function within the land plants and the mechanisms regulating bryophyte gametophytic shoot development are largely unknown.', 'We have found that treating gametophytic shoots of the moss Physcomitrella patens with exogenous auxins and auxin transport inhibitors disrupts apical function and leaf development. Two plasma membrane-targeted PIN proteins are expressed in leafy shoots, and pin mutants resemble plants treated with auxins or auxin transport inhibitors. PIN-mediated auxin transport regulates apical cell function, leaf initiation, leaf shape, and shoot tropisms in moss gametophytes. pin mutant sporophytes are sometimes branched, reproducing a phenotype only previously seen in the fossil record and in rare natural moss variants.",
            "output": [
                "Do plasma membrane-targeted PIN proteins drive shoot development in a moss?"
            ]
        },
        {
            "id": "task847-f93dfcec6bc248f285cacf4fa6e65b0d",
            "input": "Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies associated with mutations or copy number variations in over 70 genes encoding proteins with fundamental roles in the development and function of Schwann cells and peripheral axons. Here, we used iPSC-derived cells to identify common pathophysiological mechanisms in axonal CMT.', 'iPSC lines from patients with two distinct forms of axonal CMT (CMT2A and CMT2E) were differentiated into spinal cord motor neurons and used to study axonal structure and function and electrophysiological properties in vitro.', 'iPSC-derived motor neurons exhibited gene and protein expression, ultrastructural and electrophysiological features of mature primary spinal cord motor neurons. Cytoskeletal abnormalities were found in neurons from a CMT2E (NEFL) patient and corroborated by a mouse model of the same NEFL point mutation. Abnormalities in mitochondrial trafficking were found in neurons derived from this patient, but were only mildly present in neurons from a CMT2A (MFN2) patient. Novel electrophysiological abnormalities, including reduced action potential threshold and abnormal channel current properties were observed in motor neurons derived from both of these patients.",
            "output": [
                "Do axonal Charcot-Marie-Tooth disease patient-derived motor neurons demonstrate disease-specific phenotypes including abnormal electrophysiological properties?"
            ]
        },
        {
            "id": "task847-b0b8997e05394a83a1f143f71ed539e6",
            "input": "To study the gastroprotective effect and in vivo antioxidant potential of a standardized iridoid fraction from B. prionitis leaves (BPE) against different gastric ulcer models in rats.', 'The standardized iridoid fraction from BPE at 50, 100, and 200 mg/kg body weight was administered orally, twice daily for 5 days for prevention from aspirin, ethanol, cold-restraint stress (CRS), and pylorus ligation (PL)-induced ulcers. Estimation of the antioxidant enzyme activity was carried out in a CRS-induced ulcer model, and various gastric secretion parameters including volume of gastric juice, acid output, and pH value were estimated in the PL-induced ulcer model.', 'BPE showed a dose-dependent ulcer protective effect in PL (18.67%-66.26% protection), aspirin (24.65%-63.25% protection), CRS (20.77%-59.42% protection), and EtOH (16.93%-77.04% protection)-induced ulcers. BPE treatment in PL-rats showed a decrease in acid-pepsin secretion, and enhanced mucin and mucosal glycoproteins. However, BPE reduced the ulcer index with significant decrease in LPO (P < 0.01-0.001), SOD (P < 0.01-0.001), and an increase in CAT (P < 0.01-0.001), activity in the CRS-induced model.",
            "output": [
                "Does gastroprotective effect of the iridoid fraction from Barleria prionitis leave on experimentally-induced gastric ulceration?"
            ]
        },
        {
            "id": "task847-9c6bd5526e9f49c3a3df6c12ea252487",
            "input": "Radiation induces an important apoptosis response in irradiated organs. The objective of this study was to investigate the radioprotective effect of tetramethylpyrazine (TMP) on irradiated lymphocytes and discover the possible mechanism of protection.', 'Lymphocytes were pretreated for 12 h with TMP (25-200 \u03bcmol\u00b7L(-1)) and then exposed to 4 Gy radiation. Cell apoptosis and the signaling pathway were analyzed.', 'Irradiation increased cell death, DNA fragmentation, activated caspase activation and cytochrome c translocation, downregulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax). Pretreated with TMP significantly reversed this tendency. Several anti-apoptotic characteristics of TMP, including the ability to increase cell viability, inhibit caspase-9 activation, and upregulate Bcl-2 and down-regulate Bax in 4Gy-irradiated lymphocytes were determined. Signal pathway analysis showed TMP could translate nuclear factor-\u03baB (NF-\u03baB) from cytosol into the nucleus.",
            "output": [
                "Does tetramethylpyrazine protect lymphocytes from radiation-induced apoptosis through nuclear factor-\u03baB?"
            ]
        },
        {
            "id": "task847-88c5583f0672435ea766ad8eac07adf9",
            "input": "Insomnia has been associated with mortality risk, but whether this association is different in subjects with persistent vs intermittent insomnia is unclear. Additionally, the role of systemic inflammation in such an association is unknown.', 'We used data from a community-based cohort to determine whether persistent or intermittent insomnia, defined based on persistence of symptoms over a 6-year period, was associated with death during the following 20 years of follow-up. We also determined whether changes in serum C-reactive protein (CRP) levels measured over 2 decades between study initiation and insomnia determination were different for the persistent, intermittent, and never insomnia groups. The results were adjusted for confounders such as age, sex, body mass index, smoking, physical activity, alcohol, and sedatives.', 'Of the 1409 adult participants, 249 (18%) had intermittent and 128 (9%) had persistent insomnia. During a 20-year follow-up period, 318 participants died (118 due to cardiopulmonary disease). In adjusted Cox proportional-hazards models, participants with persistent insomnia (adjusted hazards ratio [HR] 1.58; 95% confidence interval [CI], 1.02-2.45) but not intermittent insomnia (HR 1.22; 95% CI, 0.86-1.74) were more likely to die than participants without insomnia. Serum CRP levels were higher and increased at a steeper rate in subjects with persistent insomnia as compared with intermittent (P\\xa0= .04) or never (P\\xa0=\\xa0.004) insomnia. Although CRP levels were themselves associated with increased mortality (adjusted HR 1.36; 95% CI, 1.01-1.82; P\\xa0= .04), adjustment for CRP levels did not notably change the association between persistent insomnia and mortality.",
            "output": [
                "Is persistent insomnia associated with mortality risk?"
            ]
        },
        {
            "id": "task847-39d1b32ac030424cb371e0bdbb5846f1",
            "input": "The safety of Deltamethrin (DM) has been raised as a point of concern. The current investigation was envisaged to explore the responsiveness of oxidative stress parameters, DNA fragmentation and expression levels of TP53, cycloxygenase 2 (COX2) and cytochrome p4502E1 (CYP2E1) as toxicological endpoint in rats treated with DM. as well as attention was provided to the neuroprotective effect of vitamin E (VE).', 'Four different groups of rats were used in this study, group I served as control, group II received DM (0.6 mg/kg BW), group III received both DM plus VE and finally group IV received VE only (200 mg/kg BW). The treatment regimen was extending for one month for all groups and the brain tissues were collected for further analysis.', 'The obtained results showed a highly statistically significant increase in lipid peroxidation (LPO) content, nitric oxide concentration, and DNA fragmentation percentage and expression level of CYP2E1, TP53 and COX2 genes, in addition statistical significant reduction in total antioxidant capacity in DM treated group as compared to control were detected. Oral administration of VE attenuated the neurotoxic effects of DM through improvement of oxidative status, DNA fragmentation percentage and suppressing the expression level of CYP2E1, TP53 and COX2 genes.",
            "output": [
                "Does vitamin E attenuate neurotoxicity induced by deltamethrin in rats?"
            ]
        },
        {
            "id": "task847-05712bcaa33a47a3817ff701c59afe45",
            "input": "Glial cell line-derived neurotrophic factor (GDNF) and N-cadherin interact to transduce intracellular signals. However, the specific molecular mechanisms of this interaction are unclear. This study attempted to detect changes in GDNF-induced \u03b2-catenin phosphorylation and nuclear translocation in C6 glioma cells.', 'C6 glioma cells were treated with GDNF (70 ng/mL) and membrane and cytoplasmic proteins were extracted. A N-cadherin antibody was used for co-immunoprecipitation (co-IP). Western blot analysis using the co-IP protein was completed using antibodies for \u03b2-catenin, Src and \u03b2-actin. Immunocytochemistry was conducted with the same antibodies. To determine if Src induced phosphorylation of \u03b2-catenin Tyr-654, Western blot analysis was also performed on nuclear proteins from C6 cells treated with tyrosine kinase inhibitor PP2 using then p- \u03b2-catenin antibody.', 'After induced by GDNF, C6 cell membrane \u03b2-catenin was phosphorylated at Tyr-654 and subsequently separated from the N-cadherin/\u03b2-catenin complex. Further study confirmed that the induction by GDNF significantly increased cytoplasmic and nuclear expression of phospho-\u03b2-catenin (Tyr-654) in C6 glioma cells. There was also an increase in the binding of non-receptor protein kinase Src with N-cadherin on the inner cell membrane surface. Src induced phosphorylation of \u03b2-catenin Tyr-654 induced by GDNF decreased significantly.",
            "output": [
                "Does glial cell line-derived neurotrophic factor promote \u03b2-catenin phosphorylation and nuclear translocation in glioma cells?"
            ]
        },
        {
            "id": "task847-8c0bb31c57be4c5b9b6259f4c6e4eaad",
            "input": "As the primary immune cells of the central nervous system, microglia contribute to development, homeostasis, and plasticity of the central nervous system, in addition to their well characterized roles in the foreign body and inflammatory responses. Increasingly, inappropriate activation of microglia is being reported as a component of inflammation in neurodegenerative and neuropsychiatric disorders. The statin class of cholesterol-lowering drugs have been observed to have anti-inflammatory and protective effects in both neurodegenerative diseases and ischemic stroke, and are suggested to act by attenuating microglial activity.', 'We sought to investigate the effects of simvastatin treatment on the secretory profile and phagocytic activity of primary cultured rat microglia, and to dissect the mechanism of action of simvastatin on microglial activity. Simvastatin treatment altered the release of cytokines and trophic factors from microglia, including interleukin-1-\u03b2, tumour necrosis factor-\u03b1, and brain derived neurotrophic factor in a cholesterol-dependent manner. Conversely, simvastatin inhibited phagocytosis in microglia in a cholesterol-independent manner.",
            "output": [
                "Does statin treatment affect cytokine release and phagocytic activity in primary cultured microglia through two separable mechanisms?"
            ]
        },
        {
            "id": "task847-5093d3b11db74d379d24570735056494",
            "input": "Rac1 upregulation has been implicated in salt-sensitive hypertension as a modulator of mineralocorticoid receptor (MR) activity. Rac1 could affect the expression of oxidative stress markers, such as hemoxigenase-1 (HO-1) or nuclear factor-B (NF-\u03baB), and the expression of neutrophil gelatinase-associated lipocalin (NGAL), a cytokine upregulated upon MR activation.', 'We evaluated RAC1 expression in relation of high salt intake and association with MR, NGAL, HO-1, and NF-\u03baB expression, mineralo- and glucocorticoids levels, and inflammatory parameters.', 'We studied 147 adult subjects. A food survey identified the dietary sodium (Na) intake. RAC1 expression was considered high or low according to the value found in normotensive subjects with low salt intake. We determined the gene expression of RAC1, MR, NGAL, HO-1, NF-\u03baB, and 18S, isolated from peripheral leukocytes. We measured aldosterone, cortisol, sodium, potassium excretion, metalloproteinase (MMP9 y MMP2), and C-reactive protein.', 'We identified 126 subjects with high Na-intake, 18 subjects had high, and 108 low-RAC1 expression. The subjects with high-RAC1 expression showed a significant increase in MR (P = 0.0002), NGAL (P < 0.0001) HO-1 (P = 0.0004), and NF-\u03baB (P < 0.0001) gene expression. We demonstrated an association between RAC1 expression and MR (R sp 0.64; P < 0.0001), NGAL (R sp 0.48; P < 0.0001), HO-1 (R sp 0.53; P < 0.0001), and NF-\u03baB (R sp0.52; P < 0.0001). We did not identify any association between RAC1 and clinical or biochemical variables.",
            "output": [
                "Are the Expression of RAC1 and Mineralocorticoid Pathway-Dependent Genes Associated With Different Responses to Salt Intake?"
            ]
        },
        {
            "id": "task847-5b7be66908e74fe0a4d03f5f6e721b90",
            "input": "To investigate how statin use is associated with the probability of having an abnormal screening prostate-specific antigen (PSA) result according to common PSA thresholds for biopsy (>2.5, >4.0, and >6.5 ng/mL).', 'We conducted a cross-sectional study of 323,426 men aged \u226565 years who had a screening PSA test in 2003 at a Veterans Affairs facility. The primary predictor was the use of statin medications at the time of index screening PSA test. The main outcome was the screening PSA value. Poisson regressions were performed to calculate adjusted relative risks for having an abnormal screening PSA result according to statin usage.', 'Percentages of men with PSA results exceeding commonly used thresholds of >2.5, >4.0, and >6.5 ng/mL were 21.0%, 7.6%, and 1.6%, respectively. These percentages decreased with statin use, increasing statin dose, duration of statin use, and potency of the statin. For example, after adjusting for age, the percentage of men having a PSA level >4.0 ng/mL ranged from 8.2% in non-statin users to 6.2% in men prescribed with >40 mg of simvastatin dose. Adjusted relative risks of having a PSA level >4.0 ng/mL were 0.89 (95% confidence interval [CI], 0.86-0.93), 0.87 (95% CI, 0.84-0.91), and 0.83 (95% CI, 0.80-0.87), respectively for men on simvastatin dose of 5-20, >20-40, and >40 mg vs non-statin users.",
            "output": [
                "Are statin medications associated with a lower probability of having an abnormal screening prostate-specific antigen result?"
            ]
        },
        {
            "id": "task847-0ae5ee2e94be4b63bf4e6c80ec85f56b",
            "input": "Embryonic-like stem cells (ELSCs) express embryonic stem cell-specific marker genes, such as SSEA-4, Oct-4 and Nanog, and can be induced to differentiate into cells of all 3 germ layers. Our preliminary data showed that ELSCs isolated from human bone marrow express multipotent antigen markers and differentiate into multinucleated myotube-like cells more efficiently than do mesenchymal stromal cells (MSCs) isolated from the same source. We investigated the therapeutic effect of ELSCs in dystrophin/utrophin double knock-out (dko) mice, one of the Duchenne muscular dystrophy animal models, by systemically transplanting them through tail-vein injection.', 'ELSCs and MSCs were both isolated from human bone marrow. Two months after equal amounts of ELSCs or MSCs were injected through tail-vein injection, we evaluated skeletal muscle motor function and serum creatine kinase activity and measured dystrophin expression by means of immunostaining, Western blotting and semi-quantitative reverse transcriptase-polymerase chain reaction.', 'ELSCs positive for Oct-4 and Nanog-3 expressed higher levels of SSEA-4, FZD-9 and CD105 and were induced to differentiate into myotube-like cells more efficiently than did MSCs in vitro. Transplantation of ELSCs through the tail vein improved motor function and decreased serum creatine kinase activity at 2 months after cell transplantation. In addition, dystrophin protein and messenger RNA were upregulated and the skeletal muscle histology was improved in these dko mice transplanted with ELSCs.",
            "output": [
                "Does systemic delivery of human bone marrow embryonic-like stem cells improve motor function of severely affected dystrophin/utrophin-deficient mice?"
            ]
        },
        {
            "id": "task847-e10cb7b24021485a8d5c25f27a9b2c52",
            "input": "Upregulator of cell proliferation 4 (URG4) has been implicated in the oncogenesis of certain cancers. However, the correlation between URG4 expression and clinicopathological significance in human cancer remains unclear. Therefore, this study investigated its expression and clinicopathological significance in cervical cancer patients.', 'URG4 expression was examined using quantitative PCR (qPCR) and western blotting in normal cervical epithelial cells, cervical cancer cells, and eight matched pairs of cervical cancer tissues and adjacent noncancerous tissues from the same patient. In addition, immunohistochemistry (IHC) was used to examine URG4 expression in paraffin-embedded tissues from 167 cervical cancer patients (FIGO stages Ib1-IIa2). Statistical analyses were performed to evaluate associations between URG4 expression and prognostic and diagnostic factors.', 'URG4 was significantly upregulated in the cervical cancer cell lines and tissues compared with the normal cells and adjacent noncancerous cervical tissues. IHC revealed high URG4 expression in 59 out of the 167 (35.13%) cervical cancer specimens. Its expression was significantly correlated with clinical stage (P < 0.0001), tumour size (P = 0.012), T classification (P = 0.023), lymph node metastasis (P = 0.001) and vaginal involvement (P = 0.002). Patients with high URG4 expression, particularly those who received concurrent chemotherapy and radiotherapy (P < 0.0001), showed a shorter overall survival (OS) and disease-free survival (DFS) compared to those with the low expression of this protein. Multivariate analysis revealed that URG4 expression is an independent prognostic factor for cervical cancer patients.",
            "output": [
                "Is uRG4 overexpression correlated with cervical cancer progression and poor prognosis in patients with early-stage cervical cancer?"
            ]
        },
        {
            "id": "task847-f0bddbe1ce7f473d9d943295404fb827",
            "input": "In this study, we aimed to demonstrate whether the presence of fragmented QRS (fQRS) is associated with the frequency of premature ventricular contractions (PVCs).', 'We retrospectively analyzed 282 cases by 24-hour Holter monitorings (HMs) between August 2012 and February 2013. Firstly, the patients were divided into 2 groups with respect to presence of fQRS and then divided into 3 groups with respect to frequency of PVCs as Group 1: seldom PVC (<120 PVCs/day), Group 2: moderate-frequency PVC (120-720 PVCs/day), and Group 3: frequent PVC (>720 PVCs/day). We investigated the predictors of frequent PVCs by using multinomial logistic regression analysis.', 'Ninety-eight patients had fQRS. There was no difference between the 2 groups with respect to body mass index, gender, hypertension, and diabetes mellitus. Patients with fQRS were older (54.9\u00b115.6 vs. 47.0\u00b116.3, p<0.001) and had more family history of coronary artery disease (25% vs. 13%, p=0.012). Patients with fQRS was more likely to be on aspirin therapy (28.6% vs. 10.4%, p<0.001) and have a larger left atrium diameter (33.5\u00b15.7 vs. 30.4\u00b15.8, p=0.001). Presence of fQRS was significantly associated with the frequency of PVCs (for frequent PVC 27.7% vs. 7.6%, p<0.001; for moderate-frequency PVC 18.4% vs. 11.4%, p=0.012); 26.2% of Group 1 (n=202) had fQRS, 46.2% of Group 2 (n=39) had fQRS, and 65.9% of Group 3 (n=41) had fQRS. In the multinomial regression analysis, only age (odds ratio: 4.24, 95% confidence interval 2.08-8.64, p=0.001) and fQRS (odds ratio: 2.11, 95% confidence interval 1.00-4.45, p=0.05) were predictors of frequent PVCs.",
            "output": [
                "Is fragmented QRS associated with frequency of premature ventricular contractions in patients without overt cardiac disease?"
            ]
        },
        {
            "id": "task847-89492accc28149fcacd40154d3e71555",
            "input": "Inhalation of antigen in atopic asthma induces early (EAR) and late asthmatic responses (LARs), inflammatory cell infiltration and airways hyperresponsiveness (AHR). Previously, we have established a protocol of sensitisation and subsequent ovalbumin (Ova) inhalation challenge in guinea-pigs which induced these 4 features (Smith & Broadley, 2007). However, the responses of guinea-pigs to Ova challenge have recently declined, producing no LAR or AHR and diminished EAR and cells. By making cumulative modifications to the protocol, we sought to restore these features.', 'Guinea-pigs were sensitised with Ova (i.p. 100 or 150 \u03bcg) on days 1 and 5 or days 1, 4 and 7 and challenged with nebulised Ova (100 or 300 \u03bcg/ml, 1h) on day 15. Airway function was measured in conscious guinea-pigs by whole-body plethysmography to record specific airway conductance (sGaw). Airway responsiveness to aerosolized histamine (0.3mM) was determined before and 24h after Ova challenge. Bronchoalveolar lavage was performed for total and differential inflammatory cell counts. Lung sections were stained for counting of eosinophils.', 'Lack of AHR and LAR with the original protocol was confirmed. Increasing the Ova challenge concentration from 100 to 300 \u03bcg/ml restored AHR and eosinophils and increased the peak of the EAR. Increasing the number of sensitisation injections from 2 to 3 did not alter the responses. Increasing the Ova sensitisation concentration from 100 to 150 \u03bcg significantly increased total cells, particularly eosinophils. A LAR was revealed and lymphocytes and eosinophils increased when either the Al(OH)3 concentration was increased or the duration between the final sensitisation injection and Ova challenge was extended from 15 to 21 days.",
            "output": [
                "Does adjustment of sensitisation and challenge protocols restore functional and inflammatory responses to ovalbumin in guinea-pigs?"
            ]
        },
        {
            "id": "task847-bc20e3dd6a2c49f0a5465e0ee12b45c6",
            "input": "The aim of this study was to examine the growth arrest and DNA damage-inducible (Gadd45a) expression and its role in tumor progression, invasion and metastasis in oral squamous cell carcinoma (OSCC).', 'Growth arrest and DNA damage-inducible 45a distribution was detected by immunohistochemistry in tumor sections of 106 patients with primary OSCC and sections of adjacent pericancerous tissues from 60 patients among the 106. The association between the Gadd45a expression and clinical prognosis of OSCC were performed by statistical analysis. Gadd45a gene knockdown was performed in Tca8113 cells by small interfering ribonucleic acid treatment and its effects on cell cycle, and migration were detected by Flow Cytometric (Becton Dickinson, USA) and transwell chamber assay respectively.",
            "output": [
                "Is expression of growth arrest and DNA damage inducible 45a in human oral squamous cell carcinoma associated with tumor progression and clinical outcome?"
            ]
        },
        {
            "id": "task847-2cdb3d9cdc884964b1a6693cdd770a3f",
            "input": "Tissue-engineered xenografts represent a promising treatment option in heart valve disease. However, inflammatory response leading to graft failure and incomplete in vitro repopulation with recipient cells remain challenging. Shock waves (SWs) were shown to modulate inflammation and to enhance re-epithelialization. We therefore aimed to investigate whether SWs could serve as a feasible adjunct to tissue engineering.', 'Porcine aortic pieces were decellularized using sodium deoxycholate and sodium dodecylsulphate and implanted subcutaneously into C57BL/6 mice (n = 6 per group). The treatment (shock wave therapy, SWT) group received SWs (0.1 mJ/mm(2), 500 impulses, 5 Hz) for modulation of inflammatory response directly after implantation; control animals remained untreated (CTR). Grafts were harvested 72 h and 3 weeks after implantation and analysed for inflammatory cytokines, macrophage infiltration and polarization, osteoclastic activity and calcification. Transmission electron microscopy (TEM) was performed. Endothelial cells (ECs) were treated with SWs and analysed for macrophage regulatory cytokines. In an ex vivo experimental set-up, decellularized porcine aortic valve conduits were reseeded with ECs with and without SWT (0.1 mJ/mm(2), 300 impulses, 3 Hz), fibroblasts as well as peripheral blood mononuclear cells (all human) and tested in a pulsatile flow perfusion system for cell coverage.', 'Treated ECs showed an increase of macrophage migration inhibitory factor and macrophage inflammatory protein 1\u03b2, whereas CD40 ligand and complement component C5/C5a were decreased. Subcutaneously implanted grafts showed increased mRNA levels of tumour necrosis factor \u03b1 and interleukin 6 in the treatment group. Enhanced repopulation with recipient cells could be observed after SWT. Augmented macrophage infiltration and increased polarization towards M2 macrophages was observed in treated animals. Enhanced recruitment of osteoclastic cells in proximity to calcified tissue was found after SWT. Consequently, SWT resulted in decreased areas of calcification in treated animals. The reseeding experiment revealed that fibroblasts showed the best coverage compared with other cell types. Moreover, SW-treated ECs exhibited enhanced repopulation compared with untreated controls.",
            "output": [
                "Does alteration of inflammatory response by shock wave therapy lead to reduced calcification of decellularized aortic xenografts in mice\u2020?"
            ]
        },
        {
            "id": "task847-152de9c72cd745ae89247b24530a5a82",
            "input": "Detection of anaplastic lymphoma kinase (ALK)-gene rearrangements in non-small-cell lung cancer (NSCLC) is mainly performed by fluorescence in-situ hybridization (FISH). The question was raised if FISH might be replaced by immunohistochemistry (IHC) in a reliable and reproducible manner across different laboratories.', 'After calibration of the staining instruments and training of the observers to binary interpretation (positive versus negative), 15 NSCLC were independently tested for ALK protein expression by IHC only in a multicenter setting (16 institutes). Each laboratory utilized the VENTANA ALK-D5F3 IHC assay. As demonstrated by FISH the samples displayed unequivocal ALK break-positivity (6\u00d7) and negativity (7\u00d7), as well as ALK positive-\"borderline\" character (2\u00d7), which is challenging for FISH diagnosis and thus was RT-PCR-confirmed.', 'All seven ALK FISH-negative cases were homogenously scored as ALK-IHC negative. All 16 participants scored the two ALK positive-\"borderline\" samples as unequivocally positive according to their protein expression. Concordant IHC interpretation was also noticed in four of six unequivocal ALK break positive cases. In two of six some observers described a weak/heterogeneous ALK-IHC staining. This would have resulted in a subsequent ALK-testing (FISH/PCR) in a routine diagnostic setting.",
            "output": [
                "Does multicenter immunohistochemical ALK-testing of non-small-cell lung cancer show high concordance after harmonization of techniques and interpretation criteria?"
            ]
        },
        {
            "id": "task847-00fcdc4f4cdf43bd8c5a4897d338eceb",
            "input": "Surfactant proteins (SP) secreted by alveolar type 2 cells, play an essential role in maintaining the air-liquid barrier of the lung and are also involved in the opsonisation and clearance of bacteria by phagocytes. We have recently described a novel surfactant protein, SP-H (SFTA3). Expression of SP-H was earlier demonstrated to be upregulated by LPS and negatively regulated by IL-1\u03b2 and IL-23 in vitro. The influence of SP-H on phagocytosis was measured using a murine and a human phagocytic cell line and fluorescent latex beads.', 'SP-H markedly increases phagocytosis in vitro in the murine-derived alveolar macrophage cell lines MH-S and in human-derived differentiated U937 cells.",
            "output": [
                "Does the novel surfactant protein SP-H enhance the phagocytosis efficiency of macrophage-like cell lines U937 and MH-S?"
            ]
        },
        {
            "id": "task847-1d83da239759474690343c44d3518e5e",
            "input": "To find the relationship between rtPA treatment vs. MMP-9 activity, MMP-3, and TIMP-1 serum levels related to patients' neurological status during acute ischaemic stroke (IS).\", '35 IS patients were enrolled. 14 of them underwent thrombolytic therapy with Actylise (rtPA group). The serum samples were obtained at 3 time-points for rtPA group (time-point 0: 1st-4th hour of stroke; time-point 1 - immediately after rtPA administration; time-point 2 - on day 5-7 from stroke onset). Remaining patients had venous blood collection at two time-points: time-point 1 - 5th-10th hour of stroke and time-point 2 - on day 5-7 of stroke. MMP-9 was analyzed with gelatin zymography, MMP-3 and TIMP-1 serum levels were analyzed with ELISA method. NIHSS improvement ratio (IR) was calculated as a difference between NIHSS score at the admission and discharge of patient.', 'The active form of MMP-9 (86kDa) was not observed in any analyzed samples. Total MMP-9 activity was significantly elevated at time-point 1 in rtPA group in comparison with non-rtPA group. MMP-3 serum level significantly decreased during rtPA administration in comparison with non-rtPA group and it was restored at time-point 2. MMP-3 negatively correlated with IR values (p=0.06).",
            "output": [
                "Does the rtPA increase MMP-9 activity in serum during ischaemic stroke?"
            ]
        },
        {
            "id": "task847-4e1c5ca623fb4bb6bcabd0eb015800a0",
            "input": "Low-grade chronic inflammation is a cardinal feature of the metabolic syndrome, yet its pathogenesis is not well defined. The purpose of this study was to examine the role of TRAIL receptor (TR) signaling in the pathogenesis of obesity-associated inflammation using mice with the genetic deletion of TR.', 'TR knockout (TR(-/-)) mice and their littermate wild-type (WT) mice were fed a diet high in saturated fat, cholesterol and fructose (FFC) or chow. Metabolic phenotyping, liver injury, and liver and adipose tissue inflammation were assessed. Chemotaxis and activation of mouse bone marrow-derived macrophages (BMDM\u03d5) was measured.', 'Genetic deletion of TR completely repressed weight gain, adiposity and insulin resistance in FFC-fed mice. Moreover, TR(-/-) mice suppressed steatohepatitis, with essentially normal serum ALT, hepatocyte apoptosis and liver triglyceride accumulation. Gene array data implicated inhibition of macrophage-associated hepatic inflammation in the absence of the TR. In keeping with this, there was diminished accumulation and activation of inflammatory macrophages in liver and adipose tissue. TR(-/-) BMDM\u03d5 manifest reduced chemotaxis and diminished activation of nuclear factor-\u03ba B signaling upon activation by palmitate and lipopolysaccharide.",
            "output": [
                "Does tRAIL receptor deletion in mice suppress the inflammation of nutrient excess?"
            ]
        },
        {
            "id": "task847-c8d0c857ba734ac1ba1b3c020d2a6cc4",
            "input": "Up to 3% of infants with bronchiolitis under 12 months of age are hospitalised, and up to 9% require intensive care. We evaluated the costs of bronchiolitis hospitalisation, with a special focus on whether infants needed intensive care.', 'Baseline and cost data were retrospectively collected, using electronic hospital files, for 80 infants under 12 months old who were treated in the paediatric intensive care unit (PICU) for bronchiolitis during a 13-year period. We calculated the daily costs for patients admitted to the PICU and compared them with 104 admitted to inpatient wards and 56 outpatients treated in the emergency department.', 'The mean hospitalisation cost for PICU patients was \u20ac8061 (95% CI 6193-9929), compared to \u20ac1834 (1649-2020) for other inpatients and \u20ac359 (331-387) for the outpatients. The hospitalisation cost per patient was associated with length of hospital stay, but not gender, age on admission or gestational age. There was no constant increase or decrease in hospitalisation costs during the study period.",
            "output": [
                "Are hospitalisation costs for infant bronchiolitis up to 20 times higher if intensive care is needed?"
            ]
        },
        {
            "id": "task847-445b88a7cf184c0ea31d94539d1130d8",
            "input": "Hospital readmissions are costly and associated with inferior patient outcomes. There is limited knowledge related to readmissions after esophagectomy for malignancy. Our aim was to determine the impact on survival of readmission after esophagectomy.', 'This cohort study utilizes Surveillance, Epidemiology, and End Results-Medicare data (2002 to 2009). Survival, length of stay, 30-day readmissions, and discharge disposition were determined. Multivariate logistic regression models were created to examine risk factors associated with readmission.', 'In all, 1,744 patients with esophageal cancer underwent esophagectomy: 80% of patients (1,390) were male, and mean age was 73 years; 71.8% of tumors (1,251) were adenocarcinomas, and 72.5% (1,265) were distal esophageal tumors; 38% of patients (667) received induction therapy. Operative approach was transthoracic in 52.6% of patients (918) and transhiatal in 37.4% (653), and required complex reconstruction (intestinal interposition) in 9.9% (173). Stage distribution was as follows: stage I, 35.3% (616); stage II, 32.5% (566); stage III, 27.9% (487); and stage IV, 2.3% (40). Median length of stay was 13 days, hospital mortality was 9.3% (158 patients), and 30-day readmission rate was 18.6% (212 of 1,139 home discharges); 25.4% of patients (443) were discharged to institutional care facilities. Overall survival was significantly worse for patients who were readmitted (p < 0.0001, log rank test). Risk factors for readmission were comorbidity score of 3+, urgent admission, and urban residence.",
            "output": [
                "Is hospital readmission associated with poor survival after esophagectomy for esophageal cancer?"
            ]
        },
        {
            "id": "task847-66494168b1b6431fba3a8f2e0b03883f",
            "input": "The Mediterranean diet, rich in polyphenols, has shown to be cardioprotective. However the mechanisms involved remain unknown. We investigated whether supplementation with a pomegranate extract rich in polyphenols renders beneficial effects on coronary function in a clinically relevant experimental model and characterized the underlying mechanisms.', 'Pigs were fed a 10-day normocholesterolemic or hypercholesterolemic diet. Half of the animals were given a supplement of 625 mg/day of a pomegranate extract (Pomanox; 200 mg punicalagins/day). Coronary responses to escalating doses of vasoactive drugs (acetylcholine, calcium ionophore, and sodium nitroprusside) and L-NG-monomethylarginine (endothelial nitric oxide-synthase inhibitor) were measured using flow Doppler. Akt/endothelial nitric oxide-synthase axis activation, monocyte chemoattractant protein-1 expression, oxidative deoxyribonucleic acid damage in the coronary artery, and lipoprotein resistance to oxidation were evaluated.', 'In dyslipidemic animals, Pomanox supplementation prevented diet-induced impairment of endothelial relaxation, reaching vasodilatory values comparable to normocholesterolemic animals upon stimulation with acetylcholine and/or calcium ionophore. These beneficial effects were associated with vascular Akt/endothelial nitric oxide-synthase activation and lower monocyte chemoattractant protein-1 expression. Pomanox supplementation reduced systemic oxidative stress (higher high-density lipoprotein-antioxidant capacity and higher low-density lipoprotein resistance to oxidation) and coronary deoxyribonucleic acid damage. Normocholesterolemic animals elicited similar drug-related vasodilation regardless of Pomanox supplementation. All animals displayed a similar vasodilatory response to sodium nitroprusside and L-NG-monomethylarginine blunted all vasorelaxation responses except for sodium nitroprusside.",
            "output": [
                "Does polyphenol-enriched diet prevent coronary endothelial dysfunction by activating the Akt/eNOS pathway?"
            ]
        },
        {
            "id": "task847-524efdfed2994881a82e933619aa510a",
            "input": "Malnutrition is a common, hence frequently underdiagnosed condition in patients with liver cirrhosis as well as in patients with cancer and has been shown to have a negative impact on survival in these patients. Frequently applied screening tools including anthropometric measurements or laboratory parameters to screen for malnutrition are not suitable for patients with liver cirrhosis with additional pathophysiological mechanisms leading to hypoalbuminemia and edema. Prospective data on the prevalence and prognostic impact of malnutrition in patients with HCC are scarce.', 'Fifty-one consecutive patients with hepatocellular carcinoma were prospectively enrolled into this study and screened for malnutrition by anthropometric measurements, the MNA score, the NRS score, laboratory work-up, and BIA measurement. The results of the different screening tools were compared to each other and with the BIA assessment and correlated with the outcome of patients.', 'The calculation of a body mass index (BMI) was not suitable to identify malnourished patients with HCC. The MNA identified 19, the NRS score 17 patients at a risk for malnutrition. BIA revealed a reduction in relative body cell mass in 12 patients. Univariate Cox regression analyses identified tumor stage, MNA score, and phase angle obtained by BIA as significant factors with influence on survival. Multivariate analyses confirmed the phase angle at a cut-off of 4.8 to be an independent factor.",
            "output": [
                "Is malnutrition a prognostic factor in patients with hepatocellular carcinoma ( HCC )?"
            ]
        },
        {
            "id": "task847-55517479baad49208f3eac84020ca8ec",
            "input": "Histiocytoid Sweet syndrome (HSS) is a rare variant of Sweet syndrome (SS). The nature of histiocytoid cells is still uncertain.', 'We sought to offer a comprehensive overview on clinical features of HSS and further information on immunohistochemical phenotype of the infiltrate.', 'The clinical, histologic, and immunohistochemical features of 12 of our patients with HSS and all cases retrieved through a PubMed search were analyzed.', 'Lesions consisted of erythematous-violaceous papules and plaques, randomly distributed mostly on the trunk and the limbs. Three patients had myelodysplastic syndrome and 1 had a monoclonal gammopathy. The infiltrate was mainly composed of CD68(+)CD163(+)myeloperoxidase(+)myeloid cell nuclear differentiation antigen(+)CD117(-)CD15(-)CD34(-), a phenotype suggestive of M2-like macrophages. A few mature neutrophils and lymphocytes were also present. Review of all HSS cases showed no sex predominance and no extracutaneous infiltrates; inconstant presence of fever and blood neutrophilia; association with hematologic or solid neoplasms (26%), autoimmune conditions (12%), and infectious diseases (10%); and good response to steroid treatment, with rare relapses or recurrences.",
            "output": [
                "Is histiocytoid Sweet syndrome infiltrated predominantly by M2-like macrophages?"
            ]
        },
        {
            "id": "task847-a0b1af916d7d489fa6c1c28275346067",
            "input": "Bacteria often form multicellular, organized communities known as biofilms, which protect cells from a variety of environmental stresses. During biofilm formation, bacteria secrete a species-specific matrix; in Bacillus subtilis biofilms, the matrix consists of protein polymers and exopolysaccharide. Many domesticated strains of B. subtilis have a reduced ability to form biofilms, and we conducted a two-month evolution experiment to test whether laboratory culturing provides selective pressure against biofilm formation in B. subtilis.', 'Bacteria grown in two-month-long batch culture rapidly diversified their biofilm-forming characteristics, exhibiting highly diverse colony morphologies on LB plates in the initial ten days of culture. Generally, this diversity decreased over time; however, multiple types of colony morphology remained in our final two-month-old populations, both under shaking and static conditions. Notably, while our final populations featured cells that produce less biofilm matrix than did the ancestor, cells overproducing biofilm matrix were present as well. We took a candidate-gene approach to identify mutations in the strains that overproduced matrix and found point mutations in the biofilm-regulatory gene sinR. Introducing these mutations into the ancestral strain phenocopied or partially phenocopied the evolved biofilm phenotypes.",
            "output": [
                "Is sinR a mutational target for fine-tuning biofilm formation in laboratory-evolved strains of Bacillus subtilis?"
            ]
        },
        {
            "id": "task847-28c2a35b4f38483d8d3cbbb9460e481d",
            "input": "The donkey (Equus asinus) is an important domestic animal that provides a reliable source of protein and method of transportation for many human populations. However, the process of domestication and the dispersal routes of the Chinese donkey are still unclear, as donkey remains are sparse in the archaeological record and often confused with horse remains. To explore the maternal origins and dispersal route of Chinese donkeys, both mitochondrial DNA D-loop and cytochrome b gene fragments of 21 suspected donkey remains from four archaeological sites in China were amplified and sequenced.', 'Molecular methods of species identification show that 17 specimens were donkeys and three samples had the maternal genetic signature of horses. One sample that dates to about 20,000 years before present failed to amplify. In this study, the phylogenetic analysis reveals that ancient Chinese donkeys have high mitochondrial DNA diversity and two distinct mitochondrial maternal lineages, known as the Somali and Nubian lineages. These results indicate that the maternal origin of Chinese domestic donkeys was probably related to the African wild ass, which includes the Nubian wild ass (Equus africanus africanus) and the Somali wild ass (Equus africanus somaliensis). Combined with historical records, the results of this study implied that domestic donkeys spread into west and north China before the emergence of the Han dynasty. The number of Chinese domestic donkeys had increased primarily to meet demand for the expansion of trade, and they were likely used as commodities or for shipping goods along the Silk Road during the Tang Dynasty, when the Silk Road reached its golden age.",
            "output": [
                "Does ancient DNA provide new insight into the maternal lineages and domestication of Chinese donkeys?"
            ]
        },
        {
            "id": "task847-6c31d84f6f9e4058a4a9f8294faa55fb",
            "input": "Trauma centers often receive transfers from lower-level trauma centers or nontrauma hospitals. The aim of this study was to analyze the incidence and pattern of secondary overtriage to our Level I trauma center.', 'We performed a 2-year retrospective analysis of all trauma patients transferred to our Level I trauma center and discharged within 24 hours of admission. Reason for referral, referring specialty, mode of transport, and intervention details were collected. Outcomes measures were incidence of secondary overtriage as well as requirement of major or minor procedure. Major procedure was defined as surgical intervention in the operating room. Minor procedures were defined as procedures performed in the emergency department.', 'A total of 1,846 patients were transferred to our Level I trauma center, of whom 440 (24%) were discharged within 24 hours of admission. The mean (SD) age was 35 (21) years, 72% were male, and mean (SD) Injury Severity Score (ISS) 4 (4). The most common reasons for referral were extremity fractures (31%), followed by head injury (23%) and soft tissue injuries (13%).Of the 440 patients discharged within 24 hours, 380 (86%) required only observation (268 of 380) or minor procedure (112 of 380). Minor procedures were entirely consisted of fracture management (n = 47, 42%) and wound care (n = 65, 58%). The mean (SD) interfacility transfer distance was 45 (46) miles. Mean (SD) hospital charges per transfer were $12,549 ($5,863).",
            "output": [
                "Do a critical analysis of secondary overtriage to a Level I trauma center?"
            ]
        },
        {
            "id": "task847-5de38909693044128424c59f26bcad8f",
            "input": "We examined whether patients with a diagnosis of fibromyalgia have an increased risk of coronary heart disease (CHD), compared with age- and sex-matched control patients. We hypothesized that patients diagnosed with fibromyalgia are at increased risk of adverse coronary events.', 'Using a matched-cohort study design, we analyzed data retrieved from the Longitudinal Health Insurance Database 2000 released by the National Health Research Institute, Taiwan. The Longitudinal Health Insurance Database 2000 includes medical claims data and registration files for 1 million enrollees randomly selected from the 2000 Registry for Beneficiaries (n = 23.72 million) of the National Health Insurance program. Patients treated for fibromyalgia at least once a month for 3 consecutive months following their initial diagnosis were enrolled in our study. The primary end point was the composite of CHD events, including percutaneous coronary interventions and coronary artery bypass grafting procedures. A propensity score was estimated by a logistic regression method, in which the fibromyalgia status was regressed on baseline prognostic factors. The hazard ratios and the 95% confidence intervals were estimated using multivariate Cox proportional-hazards regression models while adjusting for the propensity score.', 'After adjusting for the propensity score, the patients with fibromyalgia showed a significantly higher subsequent risk of a CHD event (hazard ratio, 2.11; 95% confidence interval, 1.46-3.05; P < 0.001) than the patients without fibromyalgia.",
            "output": [
                "Is fibromyalgia associated with coronary heart disease : a population-based cohort study?"
            ]
        },
        {
            "id": "task847-0dcb8296a1de48c58f6807b4b4ba1c1c",
            "input": "Diabetic retinopathy (DR) is a retinopathy resulting from diabetes mellitus (DM) which was classified into non-proliferative DR (NPDR) and proliferative DR (PDR). Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs) that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR.', 'In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR) arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR.', 'Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC) curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%.",
            "output": [
                "Do serum miRNA biomarkers serve as a fingerprint for proliferative diabetic retinopathy?"
            ]
        },
        {
            "id": "task847-8ff7506865c7489c8c40657b1968eaef",
            "input": "Endoscopic submucosal dissection (ESD) may be very time consuming, and depending on the anesthesia, the contents of the stomach may reflux to the esophagus and cause the patient to aspirate. To prevent these situations, many practitioners suggest using an overtube, but no study has been done to evaluate the effect of the use of an overtube while performing the ESD procedure. Our aim was to investigate the effects of performing an upper gastrointestinal ESD with and without overtube.', 'Records of patients who underwent ESD were evaluated for histopathological results, complications, speed of dissection, dosages of anesthetic medications, and number of suctions performed during the procedure. The patients were classified into two depending on whether an overtube was used or not.', 'There were a total of 58 patients on which 63 upper gastrointestinal ESD procedures were performed. Regarding age, gender, localization of the lesions, duration of the procedures, dosage of propofol, histopathological results, rate of complete resection, and rate of en-bloc resection, there was no difference between the two groups (p\\xa0>\\xa00,05). But the size of the lesions, the size of the resected specimen, and the speed of dissection were statistically different in two groups (p\\xa0=\\xa00.018, p\\xa0<\\xa00.001, p\\xa0<\\xa00.001, respectively).The need for suction during the procedure was much lower in the overtube group than those with no overtube (p\\xa0<\\xa00.001).",
            "output": [
                "Does the usage of overtube have a favorable effect on endoscopic submucosal dissection?"
            ]
        },
        {
            "id": "task847-18d457b7bf8547b38b515a3418aff82d",
            "input": "The adrenal sex hormone dehydroepiandrosterone (DHEA), which is present in serum mainly as the sulfate DHEA-S, is the most abundant steroid hormone in human blood. Its levels decline dramatically with age. Despite the great amount of literature on vascular and metabolic actions of DHEA/-S, evidence for an association between DHEA/-S levels and cardiovascular events is contradictory.', 'This study tested the hypothesis that serum DHEA and DHEA-S are predictors of major coronary heart disease (CHD) and/or cerebrovascular disease (CBD) events in a large cohort of elderly men.', 'We used gas and liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based Osteoporotic Fractures in Men study in Sweden (2,416 men, ages 69 to 81 years). Complete cardiovascular clinical outcomes were available from national Swedish registers.', 'During the 5-year follow-up, 302 participants experienced a CHD event, and 225 had a CBD event. Both DHEA and DHEA-S levels were inversely associated with the age-adjusted risk of a CHD event; the hazard ratios and 95% confidence intervals per SD increase were 0.82 (0.73 to 0.93) and 0.86 (0.77 to 0.97), respectively. In contrast, DHEA/-S showed no statistically significant association with the risk of CBD events. The association between DHEA and CHD risk remained significant after adjustment for traditional cardiovascular risk factors, serum total testosterone and\\xa0estradiol, C-reactive protein, and renal function, and remained unchanged after exclusion of the first 2.6 years of follow-up to reduce reverse causality.",
            "output": [
                "Do dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men?"
            ]
        },
        {
            "id": "task847-35c1bd4b22d64502bb582bed5c4892c8",
            "input": "The aim of this study was to investigate the presence and the phenotypic expression of a gene coding for a putative collagenase. This gene (AHA_0517) was identified in Aeromonas hydrophila ATCC 7966 genome and named colAh. We constructed and characterized an Aeromonas piscicola AH-3::colAh knockout mutant. Collagenolytic activity of the wild-type and mutant strains was determined, demonstrating that colAh encodes for a collagenase. ColAh-collagen interaction was assayed by Far-Western blot, and cytopathic effects were investigated in Vero cells. We demonstrated that ColAh is a gluzincin metallopeptidase (approx. 100 kDa), able to cleave and physically interact with collagen, that contributes for Aeromonas collagenolytic activity and cytotoxicity. ColAh possess the consensus HEXXH sequence and a glutamic acid as the third zinc binding positioned downstream the HEXXH motif, but has low sequence similarity and distinct domain architecture to the well-known clostridial collagenases. In addition, these results highlight the importance of exploring new microbial collagenases that may have significant relevance for the health and biotechnological industries.",
            "output": [
                "Does aeromonas piscicola AH-3 express an extracellular collagenase with cytotoxic properties?"
            ]
        },
        {
            "id": "task847-dd2583ac1a0e48a0956e4e74816da569",
            "input": "Preoperative anemia may affect postoperative mortality and morbidity following elective cranial operations.', 'The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to identify elective cranial neurosurgical cases (2006-2012). Morbidity was defined as wound infection, systemic infection, cardiac, respiratory, renal, neurologic, and thromboembolic events, and unplanned returns to the operating room. For 30-day postoperative mortality and morbidity, adjusted odds ratios (ORs) were estimated with multivariable logistic regression.', 'Of 8015 patients who underwent elective cranial neurosurgery, 1710 patients (21.4%) were anemic. Anemic patients had an increased 30-day mortality of 4.1% versus 1.3% in non-anemic patients (P < 0.001) and an increased 30-day morbidity rate of 25.9% versus 14.14% in non-anemic patients (P < 0.001). The 30-day morbidity rates for all patients undergoing cranial procedures were stratified by diagnosis: 26.5% aneurysm, 24.7% sellar tumor, 19.7% extra-axial tumor, 14.8% intra-axial tumor, 14.4% arteriovenous malformation, and 5.6% pain. Following multivariable regression, the 30-day mortality in anemic patients was threefold higher than in non-anemic patients (4.1% vs 1.3%; OR = 2.77; 95% CI: 1.65-4.66). The odds of postoperative morbidity in anemic patients were significantly higher than in non-anemic patients (OR = 1.29; 95% CI: 1.03-1.61). There was a significant difference in postoperative morbidity event odds with a hematocrit level above (OR = 1.07; 95% CI: 0.78-1.48) and below (OR = 2.30; 95% CI: 1.55-3.42) 33% [hemoglobin (Hgb) 11 g/dl].",
            "output": [
                "Does preoperative anemia increase postoperative morbidity in elective cranial neurosurgery?"
            ]
        },
        {
            "id": "task847-2af744be4b7f4bf3b50a743ca36c34e5",
            "input": "Endothelin receptor antagonists improve pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein (BMP) type 2 receptor (BMPR2) predispose to PAH. Here, we sought to determine whether there might exist interactions between these 2 signaling pathways and their effect on the acquisition of the altered phenotype of pulmonary artery smooth muscle cells (PA-SMCs) observed in PAH.', 'Expression of BMPR2, of the BMP agonist BMP4, and of the BMP antagonists gremlin1 and gremlin2 was evaluated in lungs and in PA-SMCs from 6 PAH patients and 14 controls treated with endothelin-1. Endothelin-1 pre-treated PA-SMCs were assessed for proliferation, apoptosis, and downstream signaling activation of Smad1/5/8 and p38 mitogen-activated protein kinase (p38(MAPK)) after BMP2 treatment.', 'In PA-SMCs from PAH patients, expression of BMPR2 and BMP4 decreased, whereas expression of gremlin1 and gremlin2 increased compared with controls. Treatment of control PA-SMCs with endothelin-1 induced a dose-dependent increase in gremlin1 and gremlin2, whereas BMPR2 and BMP4 expression decreased, reaching similar levels as those observed in PAH cells. In control PA-SMCs, endothelin-1 pre-treatment reduced inhibitor of DNA binding 1 (Id1) expression and Smad1/5/8 activation induced by BMP2, whereas it enhanced p38(MAPK) activation. Moreover, BMP2 decreased serum-induced proliferation and increased the pro-apoptotic Bax/Bcl-2 ratio. These effects were attenuated by endothelin-1 pre-treatment. Endothelin-1 did not alter BMPR2 signaling in PA-SMCs from PAH patients.",
            "output": [
                "Does endothelin-Bone morphogenetic protein type 2 receptor interaction induce pulmonary artery smooth muscle cell hyperplasia in pulmonary arterial hypertension?"
            ]
        },
        {
            "id": "task847-22aca1a4006842c8a17621aaa2b6cf2b",
            "input": "To describe the long-term outcomes from a completed, multi-institutional phase 4 registry trial using the Contura multilumen balloon (CMLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer.', 'Three hundred forty-two evaluable patients were enrolled by 23 institutions between January 2008 and February 2011. All patients received 34 Gy in 10 fractions, delivered twice daily. Rigorous target coverage and normal tissue dose constraints were observed.', 'The median follow-up time was 36 months (range, 1-54 months). For the entire patient cohort of 342 patients, 10 patients experienced an ipsilateral breast tumor recurrence (IBTR). Eight of these IBTR were classified as true recurrences/marginal miss (TRMM), and 2 were elsewhere failures (EF). Local recurrence-free survival was 97.8% at 3 years. For the entire cohort, 88% of patients had good to excellent overall cosmesis. The overall incidence of infection was 8.5%. Symptomatic seroma was reported in only 4.4% of patients. A separate analysis was performed to determine whether improved outcomes would be observed for patients treated at high-volume centers with extensive brachytherapy experience. Three IBTR were observed in this cohort, only 1 of which was classified as a TRMM. Local recurrence-free survival at high-volume centers was 98.1% at 3 years. Overall cosmetic outcome and toxicity were superior in patients treated at high-volume centers. In these patients, 95% had good to excellent overall cosmesis. Infection was observed in only 2.9% of patients, and symptomatic seroma was reported in only 1.9%.",
            "output": [
                "Do long-term results from the Contura multilumen balloon breast brachytherapy catheter phase 4 registry trial?"
            ]
        },
        {
            "id": "task847-f8373061e566439b90ffff5248dd669a",
            "input": "Selenium deficiency has been shown to affect the neurological development in animals, but human research in this area is scarce. We aimed to assess the impact of selenium status during pregnancy on child development at 1.5 years of age.', \"This prospective cohort study was nested into a food and micronutrient supplementation trial (MINIMat) conducted in rural Bangladesh. Using inductively coupled plasma mass spectrometry, we measured selenium concentrations in erythrocyte fraction of blood collected from 750 mothers at gestational week 30, and calculated \u03bcg per g hemoglobin. A revised version of Bayley Scales of Infant Development was used to assess children's mental and psychomotor development. A Bangladeshi version of MacArthur's Communicative Development Inventory was used to assess language comprehension and expression. Linear regression analyses adjusted for multiple covariates were used to assess the associations.\", \"Maternal erythrocyte selenium concentrations varied considerably, from 0.19 to 0.87 \u03bcg/g hemoglobin (median 0.46 \u03bcg/g hemoglobin), and were associated with developmental measures. An increase in erythrocyte selenium by 0.50 \u03bcg/g hemoglobin was associated with an increase in children's language comprehension by 3.7 points (0.5 standard deviations; 95% confidence interval: 0.40, 7.1; p = 0.028). The same increase in erythrocyte selenium corresponded to an increase in the girls' psychomotor development by 12 points (0.9 standard deviation; 95% confidence interval: 4.3, 19; p = 0.002), but much less in boys.",
            "output": [
                "Does selenium status in pregnancy influence children 's cognitive function at 1.5 years of age?"
            ]
        },
        {
            "id": "task847-3e3e4fe5ca87465083cefb8c5cf093ad",
            "input": "To evaluate whether the use of intraoperative dexmedetomidine (DEX) during lung cancer surgery may reduce the incidence of postoperative atrial fibrillation (POAF).', 'A retrospective study.', 'Academic hospital.', 'Seven hundred three adult patients with non-small-cell lung cancer.', \"Patients younger than 18 years of age with a history of atrial fibrillation were excluded. Episodes of atrial fibrillation were identified from electronic medical records and consisted of cardiology consultations, electrocardiogram records, and use of anti-arrhythmic medications within the postoperative admission time. The Wilcoxon rank sum test was used to evaluate the difference in a continuous variable between patient groups. Fisher's exact test or the chi-square test was used to evaluate the association between 2 categorical variables. Logistic regression models were used for multivariate analysis. Overall POAF incidence was 136 of 703 (19.35%), with a mean onset of 3.01\u00b12.03 days after surgery. Among patients, 204 (29.02%) received DEX intraoperatively. Male gender and age were strong predictors of POAF. POAF incidence was comparable between patients who were (n=93, 21.1%) and were not (n=43, 18.6%) treated with DEX (p=0.46). The mean onset time of arrhythmia was similar in both groups (DEX users: 2.93\u00b12.49 days; non-DEX users: 3.05\u00b11.79 days; p=0.146).",
            "output": [
                "Does dexmedetomidine reduce atrial fibrillation after lung cancer surgery?"
            ]
        },
        {
            "id": "task847-0c8ef0ea9019453fa19f7d31057273ba",
            "input": "The treatment of adhesive capsulitis is a dilemma for orthopaedic rehabilitation specialists. In this study, we assessed whether extracorporeal shockwave therapy (ESWT) improves the functional outcome of primary shoulder adhesive capsulitis.', 'In this prospective, randomized, controlled, single-blind clinical trial, we enrolled 40 patients with primary adhesive capsulitis to assess whether ESWT can improve the functional outcome of primary adhesive capsulitis better than oral steroid therapy. Patients were allocated to the oral steroid group or ESWT group with randomization. Functional outcome evaluations were performed using the Constant Shoulder Score (CSS) and Oxford Shoulder Score.', 'Both groups showed significant improvement in the Oxford Shoulder Score evaluation throughout the study period. In the ESWT group, the total CSS and range of motion (ROM) parameter of the CSS in the ESWT group showed significant improvement from the fourth week that was better than that in the steroid group; the activities\u2013of\u2013daily living (ADL) parameter of the CSS achieved significance and was better than that in the steroid group at the sixth week. For the steroid group, pain was significantly reduced from baseline to the fourth week of the study; ADL and ROM improved at the fourth to 12th week. For the ESWT group, ADL and ROM improvements were significant from baseline to the sixth week.",
            "output": [
                "Does extracorporeal shockwave therapy improve short-term functional outcomes of shoulder adhesive capsulitis?"
            ]
        },
        {
            "id": "task847-75b409ed9d434e888fd1300345c2e8f5",
            "input": "We investigated whether a computed tomography (CT)-based score could predict a large infarct (\u2265 80 mL) on early diffusion-weighted magnetic resonance imaging (DWI).', 'Acute stroke patients considered for endovascular therapy within 8 hours of the onset of symptoms were included. The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was determined on noncontrast CT and computed tomography angiography source images (CTA-SI). Limited collateral flow was defined as less than 50% collateral filling on CTA-SI.', 'Fifty-six patients were analyzed. National Institutes of Health Stroke Scale score was 20 (15-24) in the large infarct group and 16 (11-20) in the small infarct group (P = .049). ASPECTS on noncontrast CT and CTA-SI was 5 (3-8) and 3 (2-6) in the large infarct group and 9 (8-10) and 8 (7-9) in the small infarct group (both P < .001), respectively. Limited collateral flow was frequent in the large infarct group than in the small infarct group (92% vs. 11%, P < .001). Multivariate analysis found that CTA-SI ASPECTS less than or equal to 5 (odds ratio [OR], 40.55; 95% confidence interval [CI], 1.10-1493.44; P = .044) and limited collateral flow (OR, 114.64; 95% CI, 1.93-6812.79; P = .023) were associated with a large infarct. Absence of ASPECTS less than or equal to 5 and limited collateral flow on CTA-SI predicted absence of a large infarct with a sensitivity of .89, specificity of 1.00, positive predictive value of 1.00, and negative predictive value of .71.",
            "output": [
                "Do collateral flow and brain changes on computed tomography angiography predict infarct volume on early diffusion-weighted imaging?"
            ]
        },
        {
            "id": "task847-53acfab06b4942938fd0e8f0db1fb6a2",
            "input": "Therapeutic angiogenesis is a promising strategy for treating ischemia. Our previous work showed that endogenous endothelial tissue factor (TF) expression induces intracrine signaling and switches-on angiogenesis in microvascular endothelial cells (mECs). We have hypothesized that activated mECs could exert a further paracrine regulation through the release of TF-rich microvascular endothelial microparticles (mEMPs) and induce neovascularization of ischemic tissues.', 'Here, we describe for the first time that activated mECs are able to induce reparative neovascularization in ischemic zones by releasing TF-rich microparticles. We show in vitro and in vivo that mEMPs released by both wild-type and TF-upregulated-mECs induce angiogenesis and collateral vessel formation, whereas TF-poor mEMPs derived from TF-silenced mECs are not able to trigger angiogenesis. Isolated TF-bearing mEMPs delivered to nonperfused adductor muscles in a murine hindlimb ischemia model enhance collateral flow and capillary formation evidenced by MRI. TF-bearing mEMPs increase angiogenesis operating via paracrine regulation of neighboring endothelial cells, signaling through the \u03b21-integrin pathway Rac1-ERK1/2-ETS1 and triggering CCL2 (chemokine [C-C motif] ligand 2) production to form new and competent mature neovessels.",
            "output": [
                "Do angiogenic microvascular endothelial cells release microparticles rich in tissue factor that promotes postischemic collateral vessel formation?"
            ]
        },
        {
            "id": "task847-fb2291e73861492ba3684cef433daee6",
            "input": "To investigate the inhibitory effects of adenovirus-mediated NDRG2 on the proliferation of human renal cell carcinoma cell line OS-RC-2 in vitro.', 'NDRG2 was harvested by RT-PCR, confirmed by DNA sequencing, and then cloned into the eukaryotic expression vector pIRES2-EGFP, which encodes green fluorescent protein (GFP), to construct pIRES2-EGFP-NDRG2 plasmid. OS-RC-2 cells with NDRG2 negative expression were transfected with pIRES2-EGFP-NDRG2 plasmid. The growth of transfected OS-RC-2 cells was observed under light and fluorescence microscopes. After colony-forming cell assays, cell proliferation detection and MTT assays, the growth curves of cells in each group were plotted to investigate the inhibitory effects of adenovirus-mediated NDRG2 on the proliferation of OS-RC-2 cells. Cell cycle was determined by flow cytometry. Confocal laser scanning microscopy showed that NDRG2 protein was specifically located on subcellular organelle.', 'A eukaryotic expression vector pIRES2-EGFP-NDRG2 was successfully constructed. After NDRG2 transfection, the growth of OS-RC-2 cells was inhibited. Flow cytometry showed that cells were arrested in S phase but the peak of cell apoptosis was not present, and confocal laser scanning microscopy showed that NDRG2 protein was located in mitochondrion.",
            "output": [
                "Does adenovirus-mediated NDRG2 inhibit the proliferation of human renal cell carcinoma cell line OS-RC-2 in vitro?"
            ]
        },
        {
            "id": "task847-b65f7396aa06425bbd964d26a1c9b577",
            "input": "The purpose of this study was to examine the effects of amino acid, hydrocarbon, and polyethylene glycol (PEG) linkers on the melanoma targeting and imaging properties of (99m)Tc-labeled lactam bridge-cyclized HYNIC-linker-Nle-CycMSHhex (hydrazinonicotinamide-linker-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2) peptides.', 'Four novel peptides (HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex, and HYNIC-AocNle-CycMSHhex) were designed and synthesized. The melanocortin-1 receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The biodistribution of (99m)Tc(ethylenediaminediacetic acid [EDDA])-HYNIC-GGGNle-CycMSHhex, (99m)Tc(EDDA)-HYNIC-GSGNle-CycMSHhex, (99m)Tc(EDDA)-HYNIC-PEG2Nle-CycMSHhex, and (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h after injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were further examined because of its high melanoma uptake.', 'The inhibitory concentrations of 50% (IC50) for HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex, and HYNIC-AocNle-CycMSHhex were 0.7 \u00b1 0.1, 0.8 \u00b1 0.09, 0.4 \u00b1 0.08, and 0.3 \u00b1 0.06 nM, respectively, in B16/F1 melanoma cells. Among these four (99m)Tc-labeled peptides, (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex displayed the highest melanoma uptake (22.3 \u00b1 1.72 percentage injected dose/g) at 2 h after injection. (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex exhibited high tumor-to-normal-organ uptake ratios except for the kidneys. The tumor-to-kidney uptake ratios of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were 3.29, 3.63, and 6.78 at 2, 4, and 24 h, respectively, after injection. The melanoma lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex as an imaging probe at 2 h after injection.",
            "output": [
                "Does introduction of an 8-aminooctanoic acid linker enhance uptake of 99mTc-labeled lactam bridge-cyclized \u03b1-MSH peptide in melanoma?"
            ]
        },
        {
            "id": "task847-e108122c291b447ea4a905a8ca4ed411",
            "input": "To provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response.', 'We retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information.', 'We obtained 45 CNB and 60 surgical specimens from the 73\\xa0patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14\\xa0had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P\\xa0= .03) and for TNBC (50% vs. 100%, P\\xa0= .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8%\\xa0vs. 14.3%, P\\xa0= .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P\\xa0= .002) and in TNBC cases (P\\xa0= .008). After a median follow-up of 26.4 months, 6 patients-all with BRCAness-had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P\\xa0=\\xa0.049).",
            "output": [
                "Does bRCAness predict resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy?"
            ]
        },
        {
            "id": "task847-48bd1d1c4583457e917df41e6a7ab35b",
            "input": "Classical swine fever virus (CSFV) infection causes significant losses of pigs, which is characterized by hemorrhage, disseminated intravascular coagulation and leucopenia. The swine vascular endothelial cell is a primary target cell for CSFV. The aim of this study was to determine the role of CSFV infection in inducing oxidative stress (OS) in vascular endothelial cells.', 'We demonstrated that CSFV infection induced oxidative stress in swine umbilical vein endothelial cells (SUVECs), characterized by the induction of reactive oxygen species (ROS) production and the elevations of porcine antioxidant proteins thioredoxin (Trx), peroxiredoxin-6 (PRDX-6) and heme oxygenase-1 (HO-1) expression. Furthermore, cyclooxygenase-2 (COX-2), a pro-inflammatory protein related to oxidative stress, was up-regulated while anti-inflammatory protein peroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3), an important mediator in vascular functional regulation, was down-regulated in the CSFV infected cells. In addition, antioxidants showed significant inhibitory effects on the CSFV replication, indicating a close relationship between CSFV replication and OS induced in the host cells.",
            "output": [
                "Does classical swine fever virus induce oxidative stress in swine umbilical vein endothelial cells?"
            ]
        },
        {
            "id": "task847-df028bcef24140ae962c4b9dd315ddbe",
            "input": "Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures.', 'We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score (RAS) of E2F4 in cancer tissues, and examined how E2F4 RAS correlates with patient survival.', \"Genes in our E2F4 signature were 21-fold more likely to be correlated with breast cancer patient survival time compared to randomly selected genes. Using eight independent breast cancer datasets containing over 1,900 unique samples, we stratified patients into low and high E2F4 RAS groups. E2F4 activity stratification was highly predictive of patient outcome, and our results remained robust even when controlling for many factors including patient age, tumor size, grade, estrogen receptor (ER) status, lymph node (LN) status, whether the patient received adjuvant therapy, and the patient's other prognostic indices such as Adjuvant! and the Nottingham Prognostic Index scores. Furthermore, the fractions of samples with positive E2F4 RAS vary in different intrinsic breast cancer subtypes, consistent with the different survival profiles of these subtypes.",
            "output": [
                "Does e2F4 regulatory program predict patient survival prognosis in breast cancer?"
            ]
        },
        {
            "id": "task847-9493e60deed1415e9c67bd511576fbd6",
            "input": "To investigate the long-term surgical outcomes of the Baerveldt 250 mm2 versus Baerveldt 350 mm2 glaucoma drainage implants (GDIs) (Abbott Laboratories Inc., Abbott Park, IL) in the treatment of refractory glaucoma.', 'Comparative case study.', 'A total of 89 consecutive eyes in 86 patients treated at Dean McGee Eye Institute between January 2006 and December 2008.', 'We retrospectively reviewed patient data from the following postoperative visits: 1 week, 1 month, 2 months, 3 months, 6 months, and every 3 months thereafter. Postoperative complications were also recorded. The mean follow-up time was 40 months (range, 2-78 months) for the Baerveldt 250 mm2 group and 31 months (range, 3-75 months) for the Baerveldt 350 mm2 group.', 'The primary outcome measure was surgical success. Secondary outcome measures included visual acuity (VA), intraocular pressure (IOP), and number of medications.', 'There was no difference in surgical success (P=0.98). No significant differences were observed in VA measured using the logarithm of the minimum angle of resolution (logMAR) scale, IOP, and number of medications at the last visit (P=0.09, 0.23, and 0.82, respectively). Complication and failure rates were comparable (P=0.82 and 0.64, respectively).",
            "output": [
                "Do long-term efficacy of the Baerveldt 250 mm2 compared with the Baerveldt 350 mm2 implant?"
            ]
        },
        {
            "id": "task847-260b6adfef784d66ac00e542c2c39402",
            "input": "Self-perception of changes in body fat among HIV+ persons is associated with decreased health related quality of life in cross-sectional studies. The longitudinal impact of body fat changes on health related quality of life, while accounting for comorbidity and anatomic location or severity of body fat changes, is unknown.', 'This was a longitudinal analysis of HIV+ and HIV- Multicenter AIDS Cohort Study (MACS) participants who completed questionnaires assessing self-perceived body fat changes (baseline visit) and a health related quality of life (Short Form-36) at baseline and then \u22655 years later.', 'Relationships between body fat changes and change in Short Form-36 Physical and Mental Component Summary scores were investigated using mixed-model regression.', 'We studied 270 HIV+ and 247 HIV- men. At baseline, \u226550% of HIV+ men reported body fat changes; physical component but not mental component summary scores were lower among HIV+ men who reported moderate/severe leg or abdominal fat changes (p<0.05). At follow-up, physical component summary scores were significantly lower among men with face, leg, or abdominal fat changes compared to men without perceived fat changes (p<0.05). No significant changes were seen in mental component scores by fat change location or severity. In the final model, body fat changes at any site or severity were significant predictors of a decline in physical component summary score (p<0.05), independent of demographics or comorbidities. Mental component summary score was not associated with body fat changes, but higher mental component summary score was associated with increasing age and time.",
            "output": [
                "Is self-reported body fat change in HIV-infected men a marker of decline in physical health-related quality of life with aging , independent of co-morbidity?"
            ]
        },
        {
            "id": "task847-3f895bcba5164fd6a96edceb081ca3fe",
            "input": "Evidence shows involvement of the cerebral cortex in the pathophysiology of cluster headache (CH). Here we investigated cortical excitability in episodic CH patients by using transcranial magnetic stimulation. In 25 patients with episodic CH and 13 healthy subjects we evaluated the motor cortical response to single-pulse (ie, motor threshold, input-output curves, cortical silent period) and paired-pulse (ie, intracortical facilitation, short intracortical inhibition) transcranial magnetic stimulation in both hemispheres. Thirteen patients were evaluated outside bout and the remaining 12 patients inside bout. Our results showed increased slope of the input-output curves after stimulation of both hemispheres in patients outside bout and in the hemisphere contralateral to the headache side in patients inside bout. Increased intracortical facilitation was observed in the hemisphere ipsilateral to the headache side in patients evaluated both outside and inside bout; reduced short intracortical inhibition was observed in patients inside bout ipsilateral to the side of pain. In conclusion, we provide evidence of increased cortical excitability in episodic CH both outside and inside bout, especially in the hemisphere ipsilateral to the side of headache attacks. Our results suggest that an abnormal regulation of cortical excitability could be involved in the pathophysiology of CH.",
            "output": [
                "Does transcranial magnetic stimulation reveal cortical hyperexcitability in episodic cluster headache?"
            ]
        },
        {
            "id": "task847-29058a58f1294cea886889da966f031c",
            "input": "Motor dysfunction in complex regional pain syndrome (CRPS) is often considered a functional movement disorder. Earlier studies in patients with functional movement disorders found evidence of cortical inhibition during explicit but not implicit motor tasks, suggesting active inhibition from other brain areas. In this study, we explored whether active inhibition occurs in CRPS patients. We compared patients with CRPS with 2 control groups: healthy controls matched for age and sex, and patients whose hand was immobilized to treat a scaphoid fracture. We used transcranial magnetic stimulation to measure corticospinal excitability at rest and during motor imagery (explicit motor task) and motor observation (implicit motor task). Motor corticospinal excitation measured at rest and during implicit and explicit motor tasks was similar for CRPS patients and healthy controls. Patients with an immobilized hand showed an absence of motor cortical excitation of the corresponding hemisphere during motor imagery of tasks involving the immobilized hand, but not during motor observation. The normal motor cortical processing during motor imagery and motor observation found in the corresponding hemisphere of CPRS patients suggests that the nature of motor dysfunction in this condition differs from that described in literature for patients with functional paresis or under circumstances of limb immobilization.",
            "output": [
                "Is motor cortical activity during motor tasks normal in patients with complex regional pain syndrome?"
            ]
        },
        {
            "id": "task847-81b42b593ed842fb970dc49808ca969e",
            "input": "Elevated glutamate levels within injured muscle play important roles in muscle pain and hyperalgesia. In this study, we hypothesized that protein kinase C (PKC)-dependent TRPV1 phosphorylation contributes to the muscle mechanical hyperalgesia following activation of Group I metabotropic glutamate receptors (mGlu1/5). Mechanical hyperalgesia induced by (R,S)-3,5-dihydroxyphenylglycine (DHPG), an mGlu1/5 agonist, in the masseter muscle was attenuated by AMG9810, a specific TRPV1 antagonist. AMG9810 also suppressed mechanical hyperalgesia evoked by pharmacologic activation of PKC. DHPG-induced mechanical hyperalgesia was suppressed by pretreatment with a decoy peptide that disrupted interactions between TRPV1 and A-kinase-anchoring protein (AKAP), which facilitates phosphorylation of TRPV1. In dissociated trigeminal ganglia, DHPG upregulated serine phosphorylation of TRPV1 (S800), during which DHPG-induced mechanical hyperalgesia was prominent. The TRPV1 phosphorylation at S800 was suppressed by a PKC inhibitor. Electrophysiologic measurements in trigeminal ganglion neurons demonstrated that TRPV1 sensitivity was enhanced by pretreatment with DHPG, and this was prevented by a PKC inhibitor, but not by a protein kinase A inhibitor. These results suggest that mGlu1/5 activation in masseter afferents invokes phosphorylation of TRPV1 serine residues including S800, and that phosphorylation-induced sensitization of TRPV1 is involved in masseter mechanical hyperalgesia. These data support a role of TRPV1 as an integrator of glutamate receptor signaling in muscle nociceptors.",
            "output": [
                "Does peripheral group I metabotropic glutamate receptor activation lead to muscle mechanical hyperalgesia through TRPV1 phosphorylation in the rat?"
            ]
        },
        {
            "id": "task847-4834444509564d05b7fe2bd680c0ae27",
            "input": "Subarachnoid hemorrhage (SAH) is a devastating neurological injury associated with significant morbidity and mortality. We postulated that lipopolysaccharide (LPS) preconditioning induces neuroprotection against early brain injury (EBI) after experimental SAH.', \"72 male Sprague-Dawley rats (250 to 300 g) were used. SAH was produced by injecting autologous arterial blood into the pre-chiasmatic cistern. Rats were given an intraperitoneal injection of LPS 24 hours prior SAH. Matrix metalloproteinase 9 (MMP-9) protein expression was measured by western blot; apoptosis in the cerebral cortex were studied by terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) and 4'6-diamidino-2-phenylindole dihydrochloride (DAPI) staining at 24 h after SAH. Brain water content was also examined.\", 'MMP-9 expression was increased after SAH and decreased by LPS preconditioning at 24 h after SAH. The number of neuronal death in cortex was increased after SAH and decreased by LPS preconditioning. In addition, brain water content was attenuated by LPS preconditioning.",
            "output": [
                "Does lipopolysaccharide preconditioning induce neuroprotection against early brain injury after experimental subarachnoid hemorrhage?"
            ]
        },
        {
            "id": "task847-98ac202cf4c644c1a7ff048722f519b9",
            "input": "Our previous study suggested that N-cadherin was downregulated in hepatocellular carcinoma (HCC). Our aim in this study was to investigate the correlation between N- and E-cadherin expression in HCC and its clinical significance.', 'Eighty-six patients with HCC undergoing liver resection were retrospectively studied. N- and E-cadherin expression in HCC and adjacent liver tissue were investigated using immunohistochemistry and immunofluorescence. The correlation between the expression status of both cadherins and surgical outcomes was analyzed.', 'In 23 patients negative for E-cadherin expression, 19 of them (82.6%) were also negative for N-cadherin expression. In 30 patients with heterogeneous expression of E-cadherin, 20 of them (66.7%) also had heterogeneous expression of N-cadherin. In 33 patients with uniformly positive expression of E-cadherin, 19 of them (57.6%) also had uniformly positive expression of N-cadherin. Therefore, there was a positive correlation between expression patterns of N- and E-cadherins. Concurrent loss of both N- and E-cadherin expressions was significantly associated with absence of the tumor capsule, vascular invasion, and poor differentiation. The 1- and 3-y disease-free survival rates were 27% and 9%, respectively, and the 1- and 3-y overall survival rates were 64.3% and 14.3%, respectively, in patients with concurrent loss of both cadherins, which were significantly worse than those with concurrent uniformly positive expression or heterogeneous expression of both cadherins.",
            "output": [
                "Is loss of N-cadherin associated with loss of E-cadherin expression and poor outcomes of liver resection in hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-00575e8f85af4420aec3b58536de2858",
            "input": "To assess the activity of mTOR and downstream effector proteins in the mTOR pathway after treatment with a dual mTOR complex 1 and 2 (mTORC1/2) inhibitor (PP242) compared with that of mTOR complex 1 (mTORC1) inhibitor (rapamycin) using a xenograft tumor model.', 'Pheochromocytoma PC12 cell were xenografted into nude mice. Animals were treated with PP242 and rapamycin. Mean tumor volume was compared across groups. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining was used to detect apoptosis. Immunoblot analysis was performed to assess mTORC1/2 activity using p-Akt, p-S6, and p-4E-BP1. The expression of the antiapoptotic protein Bcl-2, pro-apoptotic protein Bax, and the mediator of angiogenesis vascular endothelial growth factor were also investigated.', 'The mean tumor volume of PP242 was significantly lower than in other groups. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling results showed that PP242 markedly increased cell apoptosis compared with other groups. Immunoblot analysis of tumor lysates treated with PP242 demonstrated inhibition of activated p-Akt. We also observed that only PP242, but not rapamycin, significantly reduced Bcl-2 expression and markedly increased Bax expression. Rapamycin decreased vascular endothelial growth factor expression, but not nearly as striking as seen in the PP242 group.",
            "output": [
                "Does the dual mTORC1 and mTORC2 inhibitor PP242 show strong antitumor activity in a pheochromocytoma PC12 cell tumor model?"
            ]
        },
        {
            "id": "task847-f53716b8d75144a5a83e407fd582bff8",
            "input": "To investigate the role of S100A3 and the effect of S100A3 inhibition on human castration-resistant prostate cancer (CRPC) cells by using in vitro and in vivo functional assays.', 'Using human CRPC cells (PC3 and DU145), S100A3 expression levels were assessed by reverse transcription-polymerase chain reaction and Western blot analysis. After S100A3-specific small interfering ribonucleic acid (RNA) treatment, cell viability was determined by Cell Counting Kit-8 assay, and apoptotic cell fractions were evaluated by flow cytometry. The invasive properties of these cells and the expression pattern of matrix metalloproteinases (MMPs) were assessed using transwell migration assays, reverse transcription-polymerase chain reaction, and gelatin zymography. Finally, the in vivo efficacy of S100A3 inhibition on human CRPC cells was investigated using human tumor xenograft models in nude mice.', 'Human CRPC cells showed overexpression of S100A3, and its suppression reduced cell viability owing to apoptotic cell death. Additionally, S100A3 inhibition decreased the invasiveness of human CRPC cells. Moreover, MMP-2 and MMP-9 were downregulated in PC3, whereas only MMP-9 was downregulated in D145 after S100A3 inhibition. In human CRPC xenograft models, we noted a marked reduction in tumor growth in mice injected with S100A3 short hairpin RNA-transfected PC3 and DU145 cells.",
            "output": [
                "Does s100A3 suppression inhibit in vitro and in vivo tumor growth and invasion of human castration-resistant prostate cancer cells?"
            ]
        },
        {
            "id": "task847-9ffe449b63df4533a9f5ffac2ef8f0a5",
            "input": "Soluble mesothelin related peptide (SMRP) was proposed as a promising diagnostic marker for malignant pleural mesothelioma (MPM). In a previous study, we found that rs1057147 within the 3' untranslated region of MSLN gene was associated with SMRP levels. Thus, we aimed to (1) confirm the previous association on a large series of volunteers and (2) test the hypothesis that the SNP could affect microRNA binding sites.\", 'The association analysis was verified in 759 subjects. Then, in silico predictions highlighted miR-611 and miR-887 as candidate miRNAs binding to the polymorphic site. Thus, chimeric constructs bearing the alternative alleles (G > A) were assayed alone or in cotransfection with the miRNA mimics, with dual luciferase reporter assay in non-MPM Met-5A cells. The miRNAs were also assayed by western blot analysis for their ability to down-regulate endogenous mesothelin in the MPM Mero-14 cell line.', 'We confirmed that, among non-MPM volunteers, GG homozygotes have the lowest SMRP levels. When the genotype is taken into account, the specificity of SMRP as biomarker improves from 79.7% to 85.3%. Dual-luciferase assays showed a significantly lower reporter activity when the vector harbored the G allele as compared to A allele. miR-887 mimic caused a reduced reporter activity of vectors harboring A or G alleles, while miR-611 was effective only on the vector harboring the G allele. Transfection of these miRNAs into Mero-14 cells significantly reduced endogenous MSLN protein.",
            "output": [
                "Does a common polymorphism within MSLN affect miR-611 binding site and soluble mesothelin levels in healthy people?"
            ]
        },
        {
            "id": "task847-929ce2804e914d189fb6641860b5eace",
            "input": "To assess the influence of vascular clamping and ischemia time on long-term post-operative renal function following partial nephrectomy (PN) for cancer in a solitary kidney.', 'This is a retrospective study including 259\\xa0patients managed by PN between 1979 and 2010 in 13\\xa0centers. Clamping use, technique choice (pedicular or parenchymal clamping), ischemia time, and peri-operative data were collected. Pre-operative and last follow-up glomerular filtration rates were compared. A multivariate analysis using a Cox model was performed to assess the impact of ischemia on post-operative chronic renal failure risk.', 'Mean tumor size was 4.0\u00b12.3cm and mean pre-operative glomerular filtration rate was 60.8\u00b118.9mL/min. One hundred and six patients were managed with warm ischemia (40.9%) and 53\\xa0patients with cold ischemia (20.5%). Thirty patients (11.6%) have had a chronic kidney disease. In multivariate analysis, neither vascular clamping (P=0.44) nor warm ischemia time (P=0.1) were associated with a pejorative evolution of renal function. Pre-operative glomerular filtration rate (P<0.0001) and blood loss volume (P=0.02) were significant independent predictive factors of long-term renal failure.",
            "output": [
                "Is [ Ischemia an independent predictive factor of chronic renal failure after partial nephrectomy in a solitary kidney in patients without pre-operative renal insufficiency ]?"
            ]
        },
        {
            "id": "task847-26d70d5e7b3c4ec69a6a3b1b6255ea71",
            "input": "The purpose of this study was to examine functional outcomes following ORIF of displaced proximal humerus fractures in patients who received brachial plexus blocks compared to those who underwent general anesthesia.', 'We retrospectively reviewed prospectively collected data on 92 patients. Patients were grouped according to anesthesia type: regional interscalene brachial plexus block, with or without general anesthesia, or general anesthesia alone. Patients were asked to complete the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and range of motion assessments at a minimum of 6-month follow-up. Plain radiographic films were obtained to assess fracture healing.', 'Forty-five (48.9%) patients with 45 proximal humerus fractures received a regional anesthetic, while 47 (51.1%) patients with 48 proximal humerus fractures had general anesthesia. No significant differences existed in demographic information or fracture type. DASH scores at the most recent follow-up were significantly better in the regional block group (38.6) compared to the general anesthesia group (53.1) (p = 0.003). The regional block group had significantly better passive and active forward elevation and external rotation range and equivalent internal rotation (p = 0.002, 0.005, 0.002, and 0.507, respectively).",
            "output": [
                "Does regional anesthesia improve outcome in patients undergoing proximal humerus fracture repair?"
            ]
        },
        {
            "id": "task847-2482a993eff249c98d5842bc737cc98a",
            "input": "The objective of this study is to compare the serum levels of Dickkopf-1 (DKK1), a natural inhibitor of Wnt signalling, with parathyroid hormone (PTH) and bone involvement in patients with rheumatoid arthritis (RA).', 'This cross-sectional study includes 154 postmenopausal women with RA and 125 healthy controls. DKK1, 25OH vitamin D (25OHD), bone turnover markers, and PTH serum levels were measured by ELISA; lumbar spine and hip bone mineral density (BMD) and the erosion score were obtained.', 'The RA patients and healthy controls were not significantly different in terms of age, body mass index, and 25OHD serum levels. The mean level of DKK1 and PTH were significantly higher in patients with RA than in healthy controls (172\u00b168 [SD] vs. 96\u00b155 pmoL/L, and 30\u00b115 vs 22\u00b111, respectively; p<0.0001). DKK1 serum levels were positively correlated with age (p<0.05) only in the healthy controls, while they were correlated with PTH serum levels only in the RA patients (p<0.0001). Among the RA patients, DKK1 levels adjusted for age, PTH and disease duration were significantly higher in patients with bone erosions (176 vs. 167 pmoL/L, respectively; p<0.05). DKK1 levels adjusted for age and PTH were negatively correlated with total hip BMD (p<0.05). In the RA patients not on treatment with bisphosphonates, DKK1 serum levels positively correlated with C-terminal telopeptides of type I collagene serum levels (p<0.05).",
            "output": [
                "Are in patients with rheumatoid arthritis , Dickkopf-1 serum levels correlated with parathyroid hormone , bone erosions and bone mineral density?"
            ]
        },
        {
            "id": "task847-9653b830d71542e38d28c2fa60f3af67",
            "input": "To assess the impact of a multimodal antiemetic protocol on postoperative nausea and vomiting (PONV) after Le Fort I osteotomy.', 'Consecutive patients undergoing Le Fort I osteotomy with or without additional procedures at a single academic institution were recruited as the intervention cohort for an institutional review board-approved prospective clinical trial with a retrospective comparison group. The intervention cohort was managed with a multimodal antiemetic protocol, including total intravenous anesthesia; prophylactic ondansetron, steroids, scopolamine, and droperidol; gastric decompression at surgery end; opioid-sparing analgesia; avoidance of morphine and codeine; prokinetic erythromycin; and fluids at a minimum of 25 mL/kg. The comparison group consisted of consecutive patients from a larger study who underwent similar surgical procedures before protocol implementation. Data, including occurrence of PONV, were extracted from medical records. Data were analyzed in bivariate fashion with the Fisher exact and Wilcoxon rank-sum tests. Logistic regression was used to compare the likelihood of nausea and vomiting in the 2 cohorts after controlling for demographic and surgical characteristics. A P value less than .05 was considered significant.', 'The intervention (n = 93) and comparison (n = 137) groups were similar in gender (58% and 65% female patients; P = .29), race (72% and 71% Caucasian; P = .85), age (median, 19 and 20 years old; P = .75), proportion of patients with known risk factors for PONV (P = .34), percentage undergoing bimaxillary surgery (60% for the 2 groups), and percentage for whom surgery time was longer than 180 minutes (63% and 59%; P = .51). Prevalence of postoperative nausea was significantly lower in the intervention group than in the comparison group (24% vs 70%; P < .0001). Prevalence of postoperative vomiting was likewise significantly lower in the intervention group (11% vs 28%; P = .0013). The likelihood that patients in the comparison group would develop nausea was 8.9 and that for vomiting was 3.7 times higher than in the intervention group.",
            "output": [
                "Does multimodal protocol reduce postoperative nausea and vomiting in patients undergoing Le Fort I osteotomy?"
            ]
        },
        {
            "id": "task847-6d6cf7c11e27430b9d4e836b0c1c254a",
            "input": "There is no consensus about the impact of a high BMI on postoperative morbidity and survival after esophagectomy. The aim of this study was to determine the influence of a high BMI on postoperative complications and survival in a large cohort of esophageal cancer patients.', 'From January 2006 to December 2012, 1,342 consecutive esophageal cancer patients who underwent esophagectomy were included in this study. Patients were divided into three groups: 950 patients were classified as normal BMI (BMI 18.5-24.9 kg/m(2)), 279 were classified as high BMI (BMI \u2265 25 kg/m(2)), and 113 as low BMI (BMI < 18.5 kg/m(2)). Multivariate logistic regression models were used to identify confounding factors associated with postoperative complications. The impact of BMI on overall survival (OS) was estimated by the Kaplan-Meier method and Cox proportional hazard models.', 'The predominance of pathological type was esophageal squamous cell carcinoma (n = 1,280, 95.4 %). Overall morbidity, mortality, and hospital stay did not differ among groups. The incidence of pneumonia was higher in patients with high BMI compared with those with normal BMI (14.7 vs. 9.9 %, P = 0.025). However, chylothorax was less frequent in high-BMI group (0.4 % in high-BMI group, 3.1 % in normal group, and 3.5 % in low group, P = 0.011). Logistic regression analysis revealed high BMI was independently associated with decreased incidence of chylothorax [HR 0.86; 95 % confidence interval 0.76-0.97]. Overweight and obese patients had significantly better overall survival than underweight patients (median OS 55.6 vs. 32.5 months, P = 0.013), while the pathological stage was significantly higher in underweight patients (P = 0.001). In multivariate analysis, T status, N status, differentiation grade, and tumor length were identified as independent prognostic factors.",
            "output": [
                "Is a high body mass index in esophageal cancer patients associated with adverse outcomes following esophagectomy?"
            ]
        },
        {
            "id": "task847-447fe0d5ea62434ebb201fc3bdd7b9d3",
            "input": "The surgical treatment method in which the peritoneal cavity is opened anteriorly and deliberately left open, hence often called \"open abdomen\" has become the standard of care in damage-control procedures as well as in the management of intra-abdominal hypertension and in severe intra-abdominal sepsis. Whereas open abdomen has been closed in two stages traditionally, a modern trend is to close the fascial layers within the initial hospitalization to avoid complications like enterocutaneous fistula and hernia formation. The aim of this study was to determine crucial factors influencing the possibility of fascial closure after open abdomen.', 'Between 2003 and 2013, 355 adult patients were treated with open abdomen in our institution. Their data were collected and retrospectively analyzed. They were divided into two groups depending on fascial closure or not (fascial closure, n\\xa0=\\xa0137 (39%) vs. non-fascial closure, n\\xa0=\\xa0218 (61%)).', 'The patients who reached fascial closure had a significantly higher rate of initially performed open abdomen (97 patients (71%) vs. 118 (54%), p\\xa0=\\xa00.002) and the periods of time until a second and a third look operation were significantly shorter (2.7\\xa0\u00b1\\xa02.5 vs. 4.2\\xa0\u00b1\\xa06.6 days, p\\xa0=\\xa00.021 and 5.6\\xa0\u00b1\\xa03.7 vs. 8.5\\xa0\u00b1\\xa08.6 days, p\\xa0=\\xa00.006). Furthermore, the presence of peritonitis (64 patients (47%) vs. 83 patients (38%), p\\xa0=\\xa00.023) and large bowel resection (74 patients (54%) vs. 90 patients (41%), p\\xa0=\\xa00.022) were significantly higher in this group. Rates of in-hospital mortality (97 patients (44%) vs. 38 patients (28%), p\\xa0=\\xa00.002) and the presence of pancreatitis (19 patients (9%) vs. 3 patients (2%), p\\xa0=\\xa00.013) were significantly higher in the non-fascial closure group.",
            "output": [
                "Are fascial closure after open abdomen : initial indication and early revisions decisive factors -- a retrospective cohort study?"
            ]
        },
        {
            "id": "task847-e43b79fe75d942b5947fe418c246c798",
            "input": "To demonstrate the feasibility of in vivo monitoring of the myogenic differentiation process from human muscle precursor cells to mature skeletal muscle tissue by measuring characteristic magnetic resonance (MR) imaging relaxation and diffusion properties as a potential noninvasive diagnostic tool in muscle cell therapy.', 'The study was approved by the ethics committee for studies in humans and the animal care committee. The hypothesis was tested by means of subcutaneous injection of human muscle precursor cells from the rectus abdominis muscle into nude mice (n = 18). Animals injected with human fibroblasts, prostate cancer cells, or collagen served as control animals (four in each group). T1, T2, T2*, and apparent diffusion coefficients (ADCs) were measured at 4.7-T MR imaging. MR imaging parameters were statistically evaluated by using analysis of variance with Bonferroni correction. The engineered muscle was characterized by means of immunofluorescence, Western blot, and contraction assays.', 'Muscle tissue in the early stages of the differentiation process exhibited distinctly higher T1 (mean \u00b1 standard deviation, 2242 msec \u00b1 116), T2 (224 msec \u00b1 18), and T2* (33.3 msec \u00b1 3.6) values and ADCs (1.53 \u00d7 10(-3) mm(2)/sec \u00b1 0.03) compared with those of skeletal muscle. The muscle precursor cells exhibited a nonspecific pattern compared with that in control animals in the early stages. During differentiation, the relaxation and diffusion parameters decreased and approached the values for mature skeletal muscle tissue: T1, 1386 msec \u00b1 88; T2, 32.0 msec \u00b1 4.3; T2*, 10.8 msec \u00b1 0.8; ADC, 1.39 \u00d7 10(-3) mm(2)/sec \u00b1 0.02 (reference erector spinae muscle tissue: T1, 1417 msec \u00b1 106; T2, 31.0 msec \u00b1 2.4; T2*, 11.3 msec \u00b1 1.7; and ADC, 1.40 \u00d7 10(-3) mm(2)/sec \u00b1 0.03).",
            "output": [
                "Does mR imaging relaxometry allow noninvasive characterization of in vivo differentiation of muscle precursor cells?"
            ]
        },
        {
            "id": "task847-13e7046db8f942e1b887cc63660bf51d",
            "input": "We aimed to test the outcome-predictive power of routine fasting glucose (FG) obtained at second day after onset in intravenous thrombolysis (IVT) acute ischemic stroke (AIS) patients.', 'We identified AIS patients presenting to our institution between December 2011 and July 2013 within 4.5 hours of onset, who received admission glucose (AG) before IVT, FG, and glycated hemoglobin (HbA1c) the second day after admission, from our prospectively recorded stroke database. Multivariate logistic regression was used to assess the association of FG and 90-day modified Rankin Scale (mRS).', 'Between December 2011 and July 2013, a total of 166 AIS patients received intravenous plasminogen activator. Of those, 119 patients who have AG before IVT, FG, and HbA1c the second day were included in the study. FG independently predicted 90-day clinical unfavorable outcome (mRS, 3-6 with an odds ratio of 1.576; 95% confidence interval [CI], 1.053-2.358; P = .027). This association was not significant in AG (P = .714), HbA1c (P = .655), and history of diabetes (P = .547). In receiver operating characteristic analysis, increased FG was associated with 90-day mRS (3-6) with an area under curve of .72, (95% CI, .65-.9; P = .001).",
            "output": [
                "Is higher fasting glucose next day after intravenous thrombolysis independently associated with poor outcome in acute ischemic stroke?"
            ]
        },
        {
            "id": "task847-e6279166cdd04f8f9bf9bc7507a73e0a",
            "input": "Recent immunohistochemical studies have demonstrated Sry-related HMG-Box gene 10 (SOX10) expression in malignant melanomas, malignant peripheral nerve sheath tumors, a subset of breast carcinomas, and gliomas. SOX10 has shown important clinical utility in its ability to detect desmoplastic and spindle cell melanomas. To date, most publications have employed a research use-only goat polyclonal SOX10 antibody for immunohistochemical staining.', 'To describe the development of a new mouse monoclonal SOX10 antibody (BC34) and evaluate its immunohistochemical staining profile in a wide range of normal and neoplastic tissues, with an emphasis on melanoma.', 'SOX10 antibody was optimized for staining using a polymer detection system and visualization with diaminobenzidine.', 'In normal tissues, SOX10 was expressed in skin melanocytes and eccrine cells, breast myoepithelial and lobular epithelial cells, salivary gland myoepithelial cells, peripheral nerve Schwann cells, and central nervous system glial cells. SOX10 was expressed in 238 of 257 melanomas (92.6%), including 50 of 51 of both spindle cell and desmoplastic melanomas (98%). SOX10 was expressed in 100% of nevi (20 of 20) and schwannomas (28 of 28). In other neoplasms, SOX10 was expressed in 18 of 109 invasive ductal breast carcinomas (16.5%). All other carcinomas were negative for SOX10. SOX10 was identified in 25 of 52 central nervous system neoplasms, primarily in astrocytomas (22 of 41; 53.7%), and in 4 of 99 various sarcomas examined (4.0%).",
            "output": [
                "Is a newly developed mouse monoclonal SOX10 antibody a highly sensitive and specific marker for malignant melanoma , including spindle cell and desmoplastic melanomas?"
            ]
        },
        {
            "id": "task847-1872c4dac201439db502c15588a05d51",
            "input": "To investigate, at a population level, whether a family history of abdominal aortic aneurysm (AAA) is independently related to increased aortic diameter and prevalence of AAA in men, and to elucidate whether the mean aortic diameter and the prevalence of AAA are different between participants with male and female relatives with AAA.', 'Observational population-based cross-sectional study.', '18,614 male participants screened for AAA in the VIVA-trial 2008-2011 with information on both family history of AAA and maximal aortic diameter.', 'Standardized ultrasound scan measurement of maximum antero-posterior aortic diameter. Family history obtained by questionnaire. Multivariate regression analysis was used to test for confounders: age, sex, smoking, comorbidity and medication.', 'From the screened cohort, 569 participants had at least one first degree relative diagnosed with AAA, and 38 had AAA. Participants with a family history of AAA (+FH) had a significantly larger mean maximum aortic diameter (20.50 mm) compared with participants without family history of AAA (-FH) (19.07 mm, p < .0001), and +FH with female relatives with AAA had significantly larger mean maximum aortic diameter (21.8 mm) than +FH with male relatives (19.9 mm, p = .007). Furthermore the prevalence of AAA was significantly higher among +FH (6.7%) compared with -FH (3.0%) with an odds ratio (OR) of 2.2 (95% CI: 1.6 to 3.2, p < .001) and +FH with female relatives with AAA had a more than two and a half times increased prevalence of AAA compared with +FH with male relatives with AAA with an OR of 2.65.",
            "output": [
                "Is abdominal aortic diameter increased in males with a family history of abdominal aortic aneurysms : results from the Danish VIVA-trial?"
            ]
        },
        {
            "id": "task847-6798e871aa6d42b2b0fce4ad6d23b9d6",
            "input": "We previously found that Dual-specificity phosphatase 6 (Dusp6) over-expression enhanced the growth-promoting effect of estrogen in endometrial adenocarcinoma cells. The aim of this study was to explore the correlation of Dusp6 expression with progestin sensitivity in atypical endometrial hyperplasia (AEH) and earlier endometrial carcinomas (EC).', 'Using immunohistochemistry study, we analyzed the expression of Dusp6 protein in AEH.', 'We found that progestin treatment was effective in 89% of AEH and 50% of EC. Before treatment, Dusp6 expression was significantly higher in progestin-sensitive AEH groups compared with progestin-resistant groups. After treatment, Dusp6 expression was significantly upregulated in progestin-sensitive groups, but not in progestin-resistant groups. Moreover, a high-dose of Dusp6 transfection significantly enhanced progestin-induced growth-inhibition in Ishikawa cells.",
            "output": [
                "Does dual-specificity phosphatase 6 predict the sensitivity of progestin therapy for atypical endometrial hyperplasia?"
            ]
        },
        {
            "id": "task847-e414d9daf12947c9afa6510cde6aba6a",
            "input": "Acromegaly has important effects on quality of life (QOL). This is the first study to measure QOL in acromegalic patients after endoscopic transsphenoidal surgery (ETSS).', \"We prospectively collected the RAND-36, Center for Epidemiologic Studies Depression (CES-D), and Pituitary QOL validated questionnaires and patients' demographics, clinical presentation, endocrine laboratory results, radiological studies, development of complications and remission rates from 20 consecutive acromegalic patients who had undergone endoscopic transphenoidal surgery.\", 'The eleven females and nine males had an average age of 42 years; 90 percent had macroadenomas and 70% had cavernous sinus invasion on their preoperative imaging. Ninety percent had improved symptoms post-operatively and 80% stated that treatment improved their QOL. Biochemically, 35% were cured, 35% had discordant results and 30% were not cured, while pan-hypopituitarism occurred in 4 patients. Physical health subscales and pituitary-related symptoms were similar to norms. \"Social,\" \"emotional health,\" and \"energy levels\" were significantly lower than norms. Seventy percent stated that their relationship with their physician \"very much so\" affected their quality of life. Pan hypopituitarism and adjuvant therapy were the most significant predictors of lower QOL subscale scores.",
            "output": [
                "Does endoscopic transphenoidal surgery for acromegaly improve quality of life?"
            ]
        },
        {
            "id": "task847-05e0c5eb576b4aa8a00e6e414aff8914",
            "input": "Previous research has demonstrated that chronic cigarette smoking and major depressive disorder (MDD) are each associated with cognitive decrements. Further, these conditions co-occur commonly, though mechanisms in the comorbid condition are poorly understood. There may be distinct, additive, or overlapping factors underlying comorbid cigarette smoking and MDD. The present study investigated the impact of smoking and MDD on executive function and emotion processing.', 'Participants (N=198) were grouped by diagnostic category (MDD and healthy controls, HC) and smoking status (ever-smokers, ES and never-smokers, NS). Participants completed the Facial Emotion Perception Test (FEPT), a measure of emotional processing, and the parametric Go/No-go task (PGNG), a measure of executive function.', 'FEPT performance was analyzed using ANCOVA with accuracy and reaction time as separate dependent variables. Repeated measures MANCOVA was conducted for PGNG with performance measure and task level as dependent variables. Analyses for each task included diagnostic and smoking group as independent variables, and gender was controlled for. Results for FEPT reveal that lower overall accuracy was found for ES relative to NS, though MDD did not differ from HC. Post-hoc analyses revealed that ES were poorer at identifying happy and sad, but not fearful or angry, faces. For PGNG, poorer performance was observed in MDD relative to HC in response time to Go targets, but there were no differences for ES and NS. Interaction of diagnosis and smoking group was not observed for performance on either task.",
            "output": [
                "Is smoking history , and not depression , related to deficits in detection of happy and sad faces?"
            ]
        },
        {
            "id": "task847-4ea9748787d84241b720388639c51014",
            "input": "Herbivory induces the activation of mitogen-activated protein kinases (MAPKs), the accumulation of jasmonates and defensive metabolites in damaged leaves and in distal undamaged leaves. Previous studies mainly focused on individual responses and a limited number of systemic leaves, and more research is needed for a better understanding of how different plant parts respond to herbivory. In the wild tobacco Nicotiana attenuata, FACs (fatty acid-amino acid conjugates) in Manduca sexta oral secretions (OS) are the major elicitors that induce herbivory-specific signaling but their role in systemic signaling is largely unknown.', 'Here, we show that simulated herbivory (adding M. sexta OS to fresh wounds) dramatically increased SIPK (salicylic acid-induced protein kinase) activity and jasmonic acid (JA) levels in damaged leaves and in certain (but not all) undamaged systemic leaves, whereas wounding alone had no detectable systemic effects; importantly, FACs and wounding are both required for activating these systemic responses. In contrast to the activation of SIPK and elevation of JA in specific systemic leaves, increases in the activity of an important anti-herbivore defense, trypsin proteinase inhibitor (TPI), were observed in all systemic leaves after simulated herbivory, suggesting that systemic TPI induction does not require SIPK activation and JA increases. Leaf ablation experiments demonstrated that within 10\\xa0minutes after simulated herbivory, a signal (or signals) was produced and transported out of the treated leaves, and subsequently activated systemic responses.",
            "output": [
                "Are fatty acid-amino acid conjugates essential for systemic activation of salicylic acid-induced protein kinase and accumulation of jasmonic acid in Nicotiana attenuata?"
            ]
        },
        {
            "id": "task847-10c91a0d8fb54a6f9b89525421df90be",
            "input": "To evaluate whether Nrf2 deficiency impacts insulin resistance and lipid accumulation in liver and white adipose tissue.', 'Lep(ob/ob) mice (OB) with targeted Nrf2 deletion (OB-Nrf2KO) were generated. Pathogenesis of obesity and type 2 diabetes was measured in C57BL/6J, Nrf2KO, OB, and OB-Nrf2KO mice. Hepatic lipid content, lipid clearance, and very low-density lipoprotein (VLDL) secretion were determined between OB and OB-Nrf2KO mice.', 'OB-Nrf2KO mice exhibited decreased white adipose tissue mass and decreased adipogenic and lipogenic gene expression compared with OB mice. Nrf2 deficiency prolonged hyperglycemia in response to glucose challenge, which was paralleled by reduced insulin-stimulated Akt phosphorylation. In OB mice, Nrf2 deficiency decreased hepatic lipid accumulation, decreased peroxisome proliferator-activated receptor \u03b3 expression and nicotinamide adenine dinucleotide phosphate (NADPH) content, and enhanced VLDL secretion. However, this observation was opposite in lean mice. Additionally, OB-Nrf2KO mice exhibited increased plasma triglyceride content, decreased HDL-cholesterol content, and enhanced apolipoprotein B expression, suggesting Nrf2 deficiency caused dyslipidemia in these mice.",
            "output": [
                "Does deficiency in Nrf2 transcription factor decrease adipose tissue mass and hepatic lipid accumulation in leptin-deficient mice?"
            ]
        },
        {
            "id": "task847-b234a4abead74e8e9e845e1993da7d56",
            "input": "Cirrhosis, or liver fibrosis, which is mainly triggered by cirrhosis fat-storing cells (CFSCs) activation, has traditionally been considered an irreversible disease. However, recent observations indicate that even advanced fibrosis is still reversible by removing the causative agents. Anti-fibrotic effects of bone marrow-derived stromal cells (BMSCs) have been demonstrated by inhibiting CFSCs via cytokines secretion; however, the mechanisms are still unclear.', 'The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated CFSCs.', 'After the co-culture of CFSCs with BMSCs supernatants with or without the addition of recombinant rat adrenomedullin (AM)/AM-specific siRNA, western blot analysis was mainly used to detect the differences of relative protein expression on CFSCs.', 'BMSC-secreted adrenomedullin (AM) effectively inhibited the proliferation and activation of CFSCs by suppressing the expression of Ang II and its binding receptor, AT1, which resulted in a reduction of p47-phox formation.",
            "output": [
                "Do bone Marrow Stromal Cells Inhibit the Activation of Liver Cirrhotic Fat-Storing Cells via Adrenomedullin Secretion?"
            ]
        },
        {
            "id": "task847-8e27438466324251aca3fb5b4e65ba1f",
            "input": "Not all patients with warfarin-related acute intracranial hemorrhage (ICH) achieve full reversal of international normalized ratio (INR) after the first dose of weight-based prothrombin complex concentrate (PCC). We sought to identify factors associated with anticoagulation reversal failure after the first dose of PCC.', 'Consecutive patients who were hospitalized with warfarin-related acute ICH at a tertiary center between 1 January 2010 and 31 December 2012 were studied. Anticoagulation reversal failure was defined as INR \u2265 1.5 after the first dose of PCC. Logistic regression was performed to determine the predictors of anticoagulation reversal failure.', 'Fifty-one patients with acute ICH received PCC for warfarin reversal using a weight-based protocol. Overall, 23 (45%) patients did not achieve full reversal of INR after the first dose. Those with anticoagulation reversal failure were obese (body mass index > 30 kg/m(2)) (41% vs. 14%, p = 0.03), had a higher initial INR (3.0 \u00b1 1.4 vs. 2.0 \u00b1 0.7, p = 0.001), and had a higher prevalence of initial INR >2.0 (22% vs. 67%, p = 0.001), compared with those who were successfully reversed. Multivariable logistic regression identified obesity (odds ratio 7.88, 95% CI 1.12 to 55.68) and initial INR >2.0 (odds ratio 12.49, 95% CI 2.27 to 68.87) as independent predictors of anticoagulation reversal failure.",
            "output": [
                "Does obesity increase risk of anticoagulation reversal failure with prothrombin complex concentrate in those with intracranial hemorrhage?"
            ]
        },
        {
            "id": "task847-cc85e9c3269a41f1aa4b92f0010fc055",
            "input": "In animal models, maternal obesity (OB) leads to augmented risk of offspring OB. While placental function is influenced by maternal habitus, the effect of maternal obesity on the interacting zones of the placenta [the labyrinth (LZ), junctional (JZ) and metrial gland (MG)] remains unknown.', 'Using a rat maternal obesity model, we conducted transcriptomic profiling of the utero-placental compartments and fetal liver (FL) at dpc 18.5, in conjunction with analyses of mRNA expression of key thyroid hormone (TH) signaling genes in the placenta, fetus and weanling offspring.",
            "output": [
                "Does rNA-seq analysis of the rat placentation site reveal maternal obesity-associated changes in placental and offspring thyroid hormone signaling?"
            ]
        },
        {
            "id": "task847-bf983057a7c544c2851000137204400e",
            "input": "Mineral bone disorder (MBD) is prevalent among chronic dialysis patients. However, relationship between different forms of vitamin D and fibroblast growth factor 23 (FGF-23) remains unclear in this population.', 'A multicenter hemodialysis cohort was assembled. We evaluated 25-OH-D and 1,25-(OH)2-D, vitamin D-binding protein, and FGF-23, in this cohort. Multiple regression analyses were performed to investigate the relationship and stewardship between different vitamin D forms and FGF-23 concentrations.', 'Chronic dialysis patients presented significantly higher FGF-23 concentrations. 25-OH-D concentrations of <20 ng/ml (deficiency), 20-30 ng/ml (insufficiency), and \u226530 ng/ml (sufficiency) were associated with progressively lower FGF-23 concentrations (p<0.01). Serum FGF-23 concentrations were significantly correlated with total (p=0.02), free (p<0.01) and bioavailable (p<0.01) 25-OH-D and total (p=0.04), free (p=0.02), and bioavailable (p=0.03) 1,25-(OH)2-D concentrations. With all 25-OH-D and 1,25-(OH)2-D forms in the regression model, we found that free 1,25-(OH)2-D outweighed all other vitamin D forms regarding its association with FGF-23 (p=0.03).",
            "output": [
                "Is serum free 1,25-dihydroxy-vitamin D more closely associated with fibroblast growth factor 23 than other vitamin D forms in chronic dialysis patients?"
            ]
        },
        {
            "id": "task847-b51170006b0543cb9cbf9c35261c3179",
            "input": "The aim of this study was to investigate PD-1/PD-L1 involvement in the hyporesponsiveness of rheumatoid arthritis (RA) synovial fluid (SF) CD4 T cells upon stimulation by thymic stromal lymphopoietin (TSLP)-primed CD1c myeloid dendritic cells (mDCs).', 'Expression of PD-1 on na\u00efve (Tn), central memory (Tcm) and effector memory (Tem) CD4 T cell subsets was assessed by flow cytometry. PD-L1 expression and its regulation upon TSLP stimulation of mDCs from peripheral blood (PB) and SF of RA patients were investigated by quantitative RT-PCR and flow cytometry. The involvement of PD-1/PD-L1 interactions in SF T cell hyporesponsiveness upon (TSLP-primed) mDC activation was determined by cell culture in the presence of PD-1 blocking antibodies, with or without interleukin 7 (IL-7) as a recognized suppressor of PD-1 expression.', 'PD-1 expression was increased on CD4 T cells derived from SF compared with PB of RA patients. TSLP increased PD-L1 mRNA expression in both PB and SF mDCs. PD-L1 protein expression was increased on SF mDCs compared with PB mDCs and was associated with T cell hyporesponsiveness. Blockade of PD-1, as well as IL-7 stimulation, during cocultures of memory T cells and (TSLP-primed) mDCs from RA patients significantly recovered T cell proliferation.",
            "output": [
                "Is synovial T cell hyporesponsiveness to myeloid dendritic cells reversed by preventing PD-1/PD-L1 interactions?"
            ]
        },
        {
            "id": "task847-bed125cebd1046ff9b2630b3a45de0a8",
            "input": "MicroRNA (miRNA) machinery regulates cancer cell behavior, and has been implicated in patients' clinical status and prognosis. We found that microRNA-29b (miR-29b) increased significantly in advanced migratory cells. However, miR-29b controls the migration ability, and its regulatory mechanism in oral squamous cell carcinoma (OSCC) remains unknown.\", 'We triggered miR-29b expression in OSCC patients and cell lines by conducting real-time quantitative PCR. We determined the functions of miR-29b in the migration of OSCC cells by using gain- and loss-of-function approaches. We elevated the target genes of miR29b through software predictions and a luciferase report assay. We used an orthotopic OSCC animal model to investigate the effects of miR29b on OSCC cell metastasis in vivo.', 'The clinical data revealed that miR-29b expression was correlated with lymph node metastasis and an advanced tumor stage in 98 OSCC patients. Furthermore, multivariate analysis revealed that miR-29b expression was significantly correlated with recurrence, and indicated poor survival. MiR-29b promoted OSCC cell migration and downregulated CX3CL1, a cell-cell adhesion regulator, which plays an essential role in miR-29b-regulated OSCC cell migration machinery. Furthermore, we found that CX3CL1 expression was correlated with lymph node metastasis and an early tumor stage in OSCC patients, and negatively correlated with miR-29b expression.",
            "output": [
                "Does microRNA-29b regulate migration in oral squamous cell carcinoma and its clinical significance?"
            ]
        },
        {
            "id": "task847-b59d5d8ee7784e92b33ffe04ff988844",
            "input": "Acid reflux has been associated with poorer outcomes after lung transplantation. Standard pre-transplant reflux assessment has not been universally adopted. Non-acid reflux may also induce a pulmonary inflammatory cascade, leading to acute and chronic rejection. Esophageal multichannel intraluminal impedance and pH testing (MII-pH) may be valuable in standard pre-transplant evaluation. We assessed the association between pre-transplant MII-pH measures and early allograft injury in lung transplant patients.', 'This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant MII-pH at a tertiary center from 2007 to 2012. Results from pre-transplant MII-pH, cardiopulmonary function testing, and results of biopsy specimen analysis of the transplanted lung were recorded. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods to assess the associations between MII-pH measures and development of acute rejection or lymphocytic bronchiolitis.', 'Thirty patients (46.7% men; age, 54.2 years) met the inclusion criteria. Pre-transplant cardiopulmonary function and pulmonary diagnoses were similar between outcome groups. Prolonged bolus clearance (hazard ratio [HR], 4.11; 95% confidence interval [CI], 1.34-12.57; p = 0.01), increased total distal reflux episodes (HR, 4.80; 95% CI, 1.33-17.25; p = 0.02), and increased total proximal reflux episodes (HR, 4.43; 95% CI, 1.14-17.31; p = 0.03) were significantly associated with decreased time to early allograft injury. Kaplan-Meier curves also demonstrated differences in time to rejection by prolonged bolus clearance (p = 0.01) and increased total distal reflux episodes (p = 0.01). Sub-group analysis including only patients with MII-pH performed off proton pump inhibitors (n = 24) showed similar results.",
            "output": [
                "Are pre-transplant impedance measures of reflux associated with early allograft injury after lung transplantation?"
            ]
        },
        {
            "id": "task847-f3625898108b4be99174113a5a33a594",
            "input": "Psoriasis is a chronic inflammatory skin disorder associated with a host of immune abnormalities. Mesenchymal stem cells (MSCs) have immunosuppressive properties and, in earlier studies, we found that the bone marrow MSCs of patients with psoriasis exhibit abnormal cytokine secretion. Since MSCs can be isolated from skin, we hypothesized that the biological characteristics of MSCs in psoriatic skin lesions might reflect the pathogenesis of psoriasis.', 'To investigate the effects of MSCs from psoriatic skin lesions on T-cell proliferation.', 'MSCs obtained from psoriatic skin lesions and healthy human skin were examined by flow cytometry and cell differentiation assays. MSCs were co-cultured with normal peripheral blood T cells to assess changes in T-cell proliferation. Concentrations of interleukin (IL)-6, IL-11, hepatocyte growth factor (HGF), and transforming growth factor (TGF)-\u03b21 in the MSC culture supernatants were measured by enzyme-linked immunosorbent assays.', 'Surface markers and differentiation capacity were similar in MSCs from both sources. MSCs in psoriatic skin lesions were weaker inhibitors of T-cell proliferation (p<0.05) and exhibited increased secretion of IL-11 and reduced secretion of IL-6 and HGF (p<0.05). Secretion of TGF-\u03b21 was unchanged (p > 0.05).",
            "output": [
                "Is lymphocyte inhibition compromised in mesenchymal stem cells from psoriatic skin?"
            ]
        },
        {
            "id": "task847-0260ea4497244135a8552f79cc998152",
            "input": "A significant proportion of school-aged children experience special health care needs (SCHN) and seek care from pediatricians with a wide range of condition types and severity levels. This study examines the learning pathways of children with established (already diagnosed at school entry) and emerging (teacher identified) SHCN from school entry through the elementary school years.', 'The Longitudinal Study of Australian Children (LSAC) is a nationally representative clustered cross-sequential sample of 2 cohorts of Australian children which commenced in May 2004. Data were analyzed from the LSAC kindergarten cohort (n\\xa0=\\xa04,983), as well as a subsample of 720 children for whom teachers also completed the Australian Early Development Index checklist, a measure of early childhood development at school entry that includes SHCN.', 'Latent class analysis was utilized to establish 3 academic trajectories from 4-5 to 10-11 years: high (24.3%), average (49.8%), and low (23.6%). Descriptive statistics revealed a trend for both children with established and emerging SHCN to fall into weaker performing learning pathways. Multinomial logistic regression focusing on those children with emerging SHCN confirmed this pattern of results, even after adjustment for covariates (relative risk 3.06, 95% confidence interval 1.03-9.10). Children who additionally had low socioeconomic standing were particularly at risk.",
            "output": [
                "Does learning trajectories of children with special health care need across the severity spectrum?"
            ]
        },
        {
            "id": "task847-dac0f6965ff947baa72f69f509931d20",
            "input": "Rhabdomyosarcoma (RMS) is a highly malignant tumour accounting for nearly half of soft tissue sarcomas in children. MicroRNAs (miRNAs) represent a class of short, non-coding, regulatory RNAs which play a critical role in different cellular processes. Altered miRNA levels have been reported in human cancers, including RMS.', 'Using deep sequencing technology, a total of 685 miRNAs were investigated in a group of alveolar RMSs (ARMSs), embryonal RMSs (ERMSs) as well as in normal skeletal muscle (NSM). Q-PCR, MTT, cytofluorimetry, migration assay, western blot and immunofluorescence experiments were carried out to determine the role of miR-378a-3p in cancer cell growth, apoptosis, migration and differentiation. Bioinformatics pipelines were used for miRNA target prediction and clustering analysis.', \"Ninety-seven miRNAs were significantly deregulated in ARMS and ERMS when compared to NSM. MiR-378 family members were dramatically decreased in RMS tumour tissue and cell lines. Interestingly, members of the miR-378 family presented as a possible target the insulin-like growth factor receptor 1 (IGF1R), a key signalling molecule in RMS. MiR-378a-3p over-expression in an RMS-derived cell line suppressed IGF1R expression and affected phosphorylated-Akt protein levels. Ectopic expression of miR-378a-3p caused significant changes in apoptosis, cell migration, cytoskeleton organization as well as a modulation of the muscular markers MyoD1, MyoR, desmin and MyHC. In addition, DNA demethylation by 5-aza-2'-deoxycytidine (5-aza-dC) was able to up-regulate miR-378a-3p levels with a concomitant induction of apoptosis, decrease in cell viability and cell cycle arrest in G2-phase. Cells treated with 5-aza-dC clearly changed their morphology and expressed moderate levels of MyHC.",
            "output": [
                "Does deep Sequencing the microRNA profile in rhabdomyosarcoma reveal down-regulation of miR-378 family members?"
            ]
        },
        {
            "id": "task847-20b99b6c589d4982b03601106de8aaac",
            "input": "Evidence-based fall prevention programs primarily attract older women, who are increasingly burdened by fall-related injuries. However, little is known about the relationship between older female participants' baseline health status and self-reported falls over the course of fall prevention interventions. Using data from A Matter of Balance/Volunteer Lay Leader Model (AMOB/VLL) workshops, this study examines female participants' sociodemographics and health indicators associated with self-reported falls at baseline and postintervention.\", 'Data were analyzed from 837 older women (M = 76.2 years) collected during the statewide AMOB/VLL dissemination in Texas. Longitudinal Poisson regression models, using the generalized estimating equation method, were used to investigate the associations of personal characteristics and health indicators with and reductions in the number of self-reported falls from baseline to postintervention.', 'Approximately 21% of participants reported falling at baseline, and the number of reported falls significantly decreased from baseline to postintervention (\u03b2 = -0.443). At baseline, more unhealthy physical days (\u03b2 = 0.022), more unhealthy mental days (\u03b2 = 0.018), and lower Falls Efficacy Scale scores (\u03b2 = -0.052) were significantly associated with more falls reported at baseline. More falls at baseline was also associated with worse program attendance (\u03b2 = -0.069). Greater improvements in Falls Efficacy Scale Scores (\u03b2 = -0.069) and decreases in unhealthy physical health days (\u03b2 = 0.026) over the course of the intervention were significantly associated with greater reductions in reported falls at postintervention, respectively.",
            "output": [
                "Does health indicators associated with fall among middle-aged and older women enrolled in an evidence-based program?"
            ]
        },
        {
            "id": "task847-e4a779e38c66402e8dc2fd2c5cec3072",
            "input": "Patient experience is an essential component of quality care. Few studies have comprehensively evaluated patient experiences of abortion care. The objectives of this study were to describe women's experiences of abortion care in their own words, and to determine themes across patient experiences.\", 'Data for this thematic analysis, a qualitative method that allows for the identification, analysis, and report of patterns or themes within data, come from a larger study of safety and quality of aspiration abortion care across 22 clinical sites. Participants completed an abortion experience survey including fixed choice questions and an open-ended question: \"Is there anything you would like to tell us about your experience?\" The data were then categorized by responses to another survey question: \"Overall, was your experience about, better, or worse than you expected?\"', 'A total of 5,214 responses were analyzed. Women reported positive abortion care experiences with the majority of women rating their experience as better than expected (n = 3,600). Two major themes that emerged from the data include clinic- and patient-level factors that impact how patients rate their experiences. Analysis of the responses categorized in the worse than expected group (n = 136) found that women primarily faulted clinic-level factors for their negative experiences, such as pain control and management, and wait time for appointments and in clinic.",
            "output": [
                "Do women know best -- findings from a thematic analysis of 5,214 surveys of abortion care experience?"
            ]
        },
        {
            "id": "task847-086390e23fab466ea3ca608b9321ab38",
            "input": "Despite concerns about increased sexual harassment and assault after the 2013 legislation repealing the ban on women in combat, little research has examined military factors that could prevent sexual harassment and assault during deployment. This study examined whether unit support, which reflects the quality of service members' relationships within their unit, protects against sexual harassment and assault during deployment.\", 'Participants were 1,674 Ohio Army National Guard service members who reported at least one deployment during a telephone survey conducted in 2008 and 2009. Participants completed measures of sexual harassment/assault, unit support, and psychosocial support. Logistic regression was used to model odds of sexual harassment/assault.', 'Approximately 13.2% of men (n = 198) and 43.5% of women (n = 74) reported sexual harassment, and 1.1% of men (n = 17) and 18.8% of women (n = 32) reported sexual assault during their most recent deployment. Greater unit support was associated with decreased odds of sexual harassment and assault.",
            "output": [
                "Does unit support protect against sexual harassment and assault among national guard soldiers?"
            ]
        },
        {
            "id": "task847-0fe7dfbd9e084c6e8971693c7952a7a4",
            "input": "Epithelial-to-mesenchymal transition (EMT) induced by TGF-\u03b21 is one of well-recognized factors contributing to renal fibrosis. However, the underlying molecular mechanisms of EMT are not fully understood. Brachyury, an evolutionarily conserved transcription factor, was recently identified as an important factor promoting EMT in human carcinoma cell lines. There is no evidence that Brachyury is involved in renal tubular EMT.', 'Our results demonstrated that Brachyury was prominently induced in TGF-\u03b21-treated human proximal tubular epithelial (HK-2) cells and that this induction was accompanied by changes characteristic of EMT. Blockage of Brachyury expression by short interfering RNA (siRNA) in HK-2 cells effectively reversed the TGF-\u03b21-induced EMT phenotype. Brachyury induction repressed E-cadherin transcription; the E-cadherin promoter contains a Brachyury binding site, and decreased expression of E-cadherin occurred in Brachyury-overexpressing cells when they were transfected with reporter constructs using the promoter. This effect was partially mediated by Slug and Snail, as knockdown of Snail and Slug by siRNA effectively reversed Brachyury-mediated EMT and partially restored E-cadherin expression. The expression of Brachyury also presented in a rat model of obstructive nephropathy and in tubulointerstitial fibrosis tissues of IgA nephropathy, suggesting that it may have a role in EMT and renal fibrosis in vivo.",
            "output": [
                "Does the T-box transcription factor Brachyury promote renal interstitial fibrosis by repressing E-cadherin expression?"
            ]
        },
        {
            "id": "task847-b09db823d5e84674b0143cf533893903",
            "input": "Hospital readmissions for pneumonia occur often and are difficult to predict. For fiscal year 2013, the Centers for Medicare & Medicaid Services readmission penalties have been applied to acute myocardial infarction, heart failure, and pneumonia. However, the overall impact of pneumonia pathogen characterization on hospital readmission is undefined.', 'This was a retrospective 6-year cohort study (August 2007 to September 2013).', 'We evaluated 9,624 patients with a discharge diagnosis of pneumonia. Among these patients, 4,432 (46.1%) were classified as having culture-negative pneumonia, 1,940 (20.2%) as having pneumonia caused by antibiotic-susceptible bacteria, 2,991 (31.1%) as having pneumonia caused by potentially antibiotic-resistant bacteria, and 261 (2.7%) as having viral pneumonia. The 90-day hospital readmission rate for survivors (n = 7,637, 79.4%) was greatest for patients with pneumonia attributed to potentially antibiotic-resistant bacteria (11.4%) followed by viral pneumonia (8.3%), pneumonia attributed to antibiotic-susceptible bacteria (6.6%), and culture-negative pneumonia (5.8%) (P < .001). Multiple logistic regression analysis identified pneumonia attributed to potentially antibiotic-resistant bacteria to be independently associated with 90-day readmission (OR, 1.75; 95% CI, 1.56-1.97; P < .001). Other independent predictors of 90-day readmission were Charlson comorbidity score > 4, cirrhosis, and chronic kidney disease. Culture-negative pneumonia was independently associated with lower risk for 90-day readmission.",
            "output": [
                "Does pneumonia Pathogen Characterization be an Independent Determinant of Hospital Readmission?"
            ]
        },
        {
            "id": "task847-f3f2cc27783949af869bf21513cc69ce",
            "input": "It is still debatable whether anemia predicts stroke outcome.', 'To describe the characteristics of patients with acute ischemic stroke (AIS) and anemia and identify whether hemoglobin status on admission is a prognostic factor of AIS outcome.', 'All 2439 patients of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) between January 2003 and June 2011 were selected. Demographics, risk factors, prestroke treatment, clinical, radiological and metabolic variables in patients with and without anemia according to the definition of the World Health Organization were compared. Functional disability and mortality were recorded up to 12 months from admission.', 'Anemic patients (17.5%) were older, had lower body mass index, higher rates of coronary artery disease (CAD), atrial fibrillation, diabetes mellitus and peripheral artery disease. Anemia was associated with more severe stroke manifestations, lower systolic and diastolic blood pressure measurements, worse estimated glomerular filtration rate and elevated C-reactive protein concentrations upon admission and with increased modified Rankin scores during the follow-up. Anemic patients had higher 7-day, 3-month and 12-month mortality, which was associated with hemoglobin status and other factors, including age, CAD, stroke severity, and baseline C-reactive levels. Hemoglobin levels were inversely associated with recurrent stroke and mortality throughout the 12-month follow-up.",
            "output": [
                "Does anemia on admission predict short- and long-term outcomes in patients with acute ischemic stroke?"
            ]
        },
        {
            "id": "task847-ae75a97e794b4e7bbf7efac42a39fc80",
            "input": "To evaluate pedestrian behavior, including reaction time, impulsivity, risk-taking, attention, and decision-making, in children with obstructive sleep apnea syndrome (OSAS) compared with healthy controls.', 'Using a case control design, 8- to 16-year-olds (n = 60) with newly diagnosed and untreated OSAS engaged in a virtual reality pedestrian environment. Sixty-one healthy children matched using a yoke-control procedure by age, race, sex, and household income served as controls.', 'Children with OSAS were riskier pedestrians than healthy children of the same age, race, and sex. Children with OSAS waited less time to cross (P < .01). The groups did not differ in looking at oncoming traffic or taking longer to decide to cross.",
            "output": [
                "Does obstructive sleep apnea syndrome increase pedestrian injury risk in children?"
            ]
        },
        {
            "id": "task847-bc9f3be2addc44f49ace6aed21ccb2b9",
            "input": "Capnography provides a continuous, non-invasive monitoring of the CO2 to assess adequacy of ventilation and provide added safety features in mechanically ventilated patients by allowing for quick identification of unplanned extubation. These monitors may allow for decreased utilization of blood gases. The objective was to determine if implementation of continuous capnography monitoring decreases the utilization of blood gases resulting in decreased charges.', 'This is a retrospective review of a quality improvement project that compares the utilization of blood gases before and after the implementation of standard continuous capnography. The time period of April 2010 to September 2010 was compared to April 2011 to September 2011. Parameters collected included total number of blood gases analyzed, cost of blood gas analysis, ventilator and patient days.', 'The total number of blood gases after the institution of end tidal CO2 monitoring decreased from 12,937 in 2009 and 13,171 in 2010 to 8,070 in 2011. The average number of blood gases per encounter decreased from 20.8 in 2009 and 21.6 in 2010 to 13.8 post intervention. The blood gases per ventilator day decreased from 4.94 in 2009 and 4.76 in 2010 to 3.30 post intervention. The total charge savings over a 6-month period was $880,496.",
            "output": [
                "Is implementation of continuous capnography associated with a decreased utilization of blood gases?"
            ]
        },
        {
            "id": "task847-7ba06f0ae484441cb904047d64bbabd8",
            "input": "Peroxisome proliferator-activated receptor gamma coactivator 1\u03b1 (PGC-1\u03b1) is a metabolic regulator induced during ischemia that prevents cardiac remodeling in animal models. The activity of PGC-1\u03b1 can be estimated in patients with ST-segment elevation acute myocardial infarction. The aim of the present study was to evaluate the value of blood PGC-1\u03b1 levels in predicting the extent of necrosis and ventricular remodeling after infarction.', 'In this prospective study of 31 patients with a first myocardial infarction in an anterior location and successful reperfusion, PGC-1\u03b1 expression in peripheral blood on admission and at 72 hours was correlated with myocardial injury, ventricular volume, and systolic function at 6 months. Edema and myocardial necrosis were estimated using cardiac magnetic resonance imaging during the first week. At 6 months, infarct size and ventricular remodeling, defined as an increase > 10% of the left ventricular end-diastolic volume, was evaluated by follow-up magnetic resonance imaging. Myocardial salvage was defined as the difference between the edema and necrosis areas.', 'Greater myocardial salvage was seen in patients with detectable PGC-1\u03b1 levels at admission (mean [standard deviation (SD)], 18.3% [5.3%] vs 4.5% [3.9%]; P = .04). Induction of PGC-1\u03b1 at 72 hours correlated with greater ventricular remodeling (change in left ventricular end-diastolic volume at 6 months, 29.7% [11.2%] vs 1.2% [5.8%]; P = .04).",
            "output": [
                "Does blood PGC-1\u03b1 Concentration predict Myocardial Salvage and Ventricular Remodeling After ST-segment Elevation Acute Myocardial Infarction?"
            ]
        },
        {
            "id": "task847-5e1de4685d704141aaa3149edc11139e",
            "input": "To describe the surgical technique for endoscopic medial orbital fat decompression in type 1 (lipogenic) Graves orbitopathy and report outcomes.', 'Retrospective interventional case review.', 'We reviewed 108 patients (206 orbits) with inactive, type 1 Graves orbitopathy without diplopia, who underwent endoscopic medial orbital fat decompression solely for proptosis reduction. Following endoscopic transethmoid medial orbital wall decompression, extraconal and intraconal orbital fat was removed with a low-suction cutting instrument. All patients were followed up for at least 12 months. Surgical time, preoperative and postoperative Hertel exophthalmometry, incidence of postoperative diplopia within 30-degree visual field in the primary gaze, and other complications were analyzed.', 'The mean surgical time was 97.7 \u00b1 16.7 minutes (67-136 minutes). The mean follow-up was 16.0 \u00b1 4.2 months (12-24 months). Preoperative and postoperative proptosis values at final review were 21.1 \u00b1 2.3 mm (17-26 mm) and 13.0 \u00b1 0.9 mm (12-15 mm), respectively (P < .001). Median reduction in proptosis was 8.0 mm with mean of 8.2 \u00b1 1.8 mm (4-11 mm). Symmetry to within 2 mm was achieved in 106 of 108 patients (98.1%). Twenty-five of 108 patients (23.1%) had diplopia within 30-degree visual field of the gaze, and 23 of these had complete resolution within 3 months, while the remaining 2 patients required squint surgery.",
            "output": [
                "Does endoscopic medial orbital fat decompression for proptosis in type 1 grave orbitopathy?"
            ]
        },
        {
            "id": "task847-daecca4f8ef74721a9c3b698a3acc6f8",
            "input": "Local anesthetics are commonly used for the treatment of a variety of tendinopathies in combination with corticosteroids injection. The goal of this study was to evaluate the effects of lidocaine and triamcinolone acetonide (TA) on cultured rat tenocytes and to determine whether there is a synergistic effect.', 'Rat patellar tendon-derived tenocytes were cultured with or without TA and lidocaine, and the culture without any additive served as the control. Cell morphology and cell viability were evaluated. Expressions of tenocyte-related genes were measured by qRT-PCR.', 'TA, when exposed to tenocytes in vitro, significantly decreased cell viability. The cells cultured with TA had a flattened shape. Moreover, the expressions of tenocyte-related genes in tenocytes were markedly decreased in the TA-treated group. We found that 1% lidocaine synergistically increased the deleterious effects of TA.",
            "output": [
                "Does lidocaine potentiate the deleterious effects of triamcinolone acetonide on tenocytes?"
            ]
        },
        {
            "id": "task847-4b5fa80a662d46d4bc34de427f0980c9",
            "input": "Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKC\u03b5) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive.', 'Given the availability of PKC\u03b5 pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKC\u03b5 in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis.', 'Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKC\u03b5 and p-PAK1 protein expression levels. PKC\u03b5 overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1.",
            "output": [
                "Is pKC\u03b5 a negative regulator of PVAT-derived vessel formation?"
            ]
        },
        {
            "id": "task847-1e47a26d64174961a8de38153015667e",
            "input": "Secondary lymphedema is a common complication of cancer therapy, but options for treating lymphedema are essentially ineffective and limited. On the contrary, lymphangiogenic growth factors accelerate lymphangiogenesis and improve lymphedema.', 'Rat tail models of lymphedema were assigned to groups that received either daily topical basic fibroblast growth factor (bFGF) or saline (control) groups. Tail volume was measured, and the function of the lymphatic system was evaluated as the fluorescence intensity of indocyanine green every 3 days. The mRNA levels of vascular endothelial growth factor (VEGF)-C and VEGF-D and the protein levels of VEGF-C were evaluated at postoperative days (PODs) 7, 14, and 28. The subcutaneous and deep areas and lymphatic vessel density were histologically determined at PODs 7, 14, and 28.', 'Tail volume was significantly larger in the control than in the bFGF group (P < 0.05). The intensity of indocyanine green fluorescence significantly decreased earlier in the bFGF group (P < 0.05). The mRNA and protein levels of VEGF-C were upregulated in the bFGF group at POD 14 (P < 0.01). Both subcutaneous and deep tissues gradually withered in both groups but more rapidly in the bFGF, than in the control group, reaching statistically significant differences in the subcutaneous and deeper areas at POD 14 (P < 0.05). Lymphatic vessel density was significantly higher in the bFGF than in the control group at POD 14 (P < 0.05).",
            "output": [
                "Does topical bFGF improve Secondary Lymphedema through Lymphangiogenesis in a Rat Tail Model?"
            ]
        },
        {
            "id": "task847-5661ddf927064d809688ae0c9e8e4cf8",
            "input": "Hemeproteins such as free myoglobin can undergo autoxidation and catalyse lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesised that serum CPK levels correlate with mortality and need for inotropic medication and duration of inotropic support, i.e. shock, among critically injured patients.', 'We conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann\u2013Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support.', \"Median CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253, 1971], p = 0.004) and in those who required inotropic medications (950 [353, 2525] vs. 469 [188, 1220], p < 0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02\u20131.19, p = 0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22\u20131.38, p < 0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p < 0.001) that remained significant in a propensity score-adjusted model.",
            "output": [
                "Is elevated serum creatine phosphokinase associated with mortality and inotropic requirement in critically injured adults?"
            ]
        },
        {
            "id": "task847-f11a391a9bc54acb9b38b413df158ad4",
            "input": "Immunosuppressant agents modulate the activity of the immune system and control adipose tissue inflammatory responses associated with obesity. Controlling adipose tissue inflammation represents an interesting option for inhibiting the low-grade inflammatory state in obese subjects and for preventing obesity-associated pathologies. In this work, we assessed the effects of thalidomide on the inflammatory response in adipose tissue as well as on systemic inflammatory marker expression in the well-established high-fat diet-induced obesity mouse model.', 'Swiss male mice were fed a high-fat diet (60% kcal from fat) for 12 weeks and received thalidomide for the last 10 days (100 mg.kg-1). Adipokine levels were measured in serum and adipose tissue by EIA and real-time quantitative PCR, respectively. Adipose tissue infiltrating macrophages were identified by immunohistochemistry and western blot analysis of F4/80 marker expression. Other inflammatory markers, such as c-Jun N-terminal kinase (JNK) phosphorylation and monocyte chemoattractant protein-1 (MCP-1) production, were also evaluated by western blot analysis. In vitro assays using 3T3-L1 adipocytes were also conducted to evaluated adipokine release.', 'In obese mice, thalidomide administration induced a reduction in adiposity accompanied by a reduction of tumor necrosis factor-\u03b1 (TNF-\u03b1), leptin and MCP-1 adipose tissue production, macrophage infiltration and JNK activation. TNF-\u03b1 and leptin serum levels were also reduced by thalidomide treatment in obese mice. In vitro, the release of basal TNF-\u03b1 and lipopolysaccharide (LPS)-induced MCP-1 was inhibited in 3T3-L1 cells.",
            "output": [
                "Does thalidomide control adipose tissue inflammation associated with high-fat diet-induced obesity in mice?"
            ]
        },
        {
            "id": "task847-bdf4851ff77a4ca287db35c327b0276f",
            "input": "The aim of the present study was to determine the effect of moderate aerobic exercise on cardiac autonomic function in type 2 diabetic patients.', 'Heart rate variability of 20 patients with type 2 diabetes was assessed. Resting electrocardiogram for the heart rate variability analysis at spontaneous respiration was recorded for 5\\xa0min in the supine position before and after 6\\xa0months of supervised aerobic training given three times per week.', 'In time domain measures, the square root of the mean of the sum of the squares of differences between adjacent R-R intervals (RMSSD; 29.7 [26-34.5] vs 46.4 [29.8-52.2]\\xa0ms, P\\xa0=\\xa00.023) and the percentage of consecutive RR intervals that differ by more than 50\\xa0ms (pNN50; 10.7 [5.5-12.7] vs 26.1 [6.6-37.2]%, P\\xa0=\\xa00.025] were significantly increased after exercise. In frequency domain measures, low frequency (62.4 [59.1-79.2] vs 37 [31.3-43.3]\\xa0nu, P\\xa0=\\xa00.003) and low frequency/high frequency (1.67 [1.44-3.8] vs 0.58 [0.46-0.59]%, P\\xa0=\\xa00.009) were significantly decreased, whereas high frequency (95 [67-149] vs 229 [98-427]\\xa0ms(2), P\\xa0=\\xa00.006) and high frequency (37.6 [20.8-40.9] vs 63 [56.7-68.7]\\xa0normalized units, P\\xa0=\\xa00.003) were significantly increased after exercise. In a Poincar\u00e9 plot, standard deviation perpendicular to the line of the Poincar\u00e9 plot (SD1; 21.3 [18.5-24.8]-33.1 [21.5-37.2]\\xa0ms, P\\xa0=\\xa00.027) was significantly increased after exercise.",
            "output": [
                "Does mild-to-moderate intensity exercise improve cardiac autonomic drive in type 2 diabetes?"
            ]
        },
        {
            "id": "task847-edce74deb3664002b6327e74c78ace91",
            "input": "To identify risk factors for hearing impairment among patients with type 2 diabetes mellitus.', 'A total of 68 patients with type 2 diabetes were enrolled between March and September of 2011. Pure-tone auditory tests were carried out for each patient at the following speech frequencies: 250; 500; 1,000; 2,000; 4,000 and 8,000\\xa0Hz. Participants were classified as having hearing impairment if the average of the pure-tone thresholds measured at 500, 1000 and 2000\\xa0Hz in either ear exceeded 25\\xa0dBHL. Demographic, anthropometric, clinical, and laboratory parameters and diabetes-associated complications were analyzed.', 'Patients were divided into those with (n\\xa0=\\xa032) and without (n\\xa0=\\xa036) hearing impairment. Hearing impaired participants had a higher urine albumin-to-creatinine ratio than those without (223.1 vs 56.5\\xa0mg/g, respectively). After adjustment for age, sex and other risk factors, the urine albumin-to-creatinine ratio remained significantly associated with hearing impairment (odds ratio 9.07, 95% confidence interval 1.73-47.43, P\\xa0=\\xa00.009). There were no significant differences in oxidative stress between the two groups.",
            "output": [
                "Is severity of hearing impairment positively associated with urine albumin excretion rate in patients with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-e85515ae0be2403ca5e2413570de6d23",
            "input": "Rasmussen encephalitis (RE) is a rare but devastating condition, mainly in children, characterized by sustained brain inflammation, atrophy of one cerebral hemisphere, epilepsy, and progressive cognitive deterioration. The etiology of RE-induced seizures associated with the inflammatory process remains unknown.', 'Cortical tissue samples from children undergoing surgical resections for the treatment of RE (n = 16) and non-RE (n = 12) were compared using electrophysiological, morphological, and immunohistochemical techniques to examine neuronal properties and the relationship with microglial activation using the specific microglia/macrophage calcium-binding protein, IBA1 in conjunction with connexins and pannexin expression.', 'Compared with non-RE cases, pyramidal neurons from RE cases displayed increased cell capacitance and reduced input resistance. However, neuronal somatic areas were not increased in size. Instead, intracellular injection of biocytin led to increased dye coupling between neurons from RE cases. By Western blot, expression of IBA1 and pannexin was increased while connexin 32 was decreased in RE cases compared with non-RE cases. IBA1 immunostaining overlapped with pannexin and connexin 36 in RE cases.",
            "output": [
                "Are in Rasmussen encephalitis , hemichannels associated with microglial activation linked to cortical pyramidal neuron coupling : a possible mechanism for cellular hyperexcitability?"
            ]
        },
        {
            "id": "task847-ad6028d6af384c6ab6f434c53fabb4c9",
            "input": "Rapa Nui (Easter Island), located in the easternmost corner of the Polynesian Triangle, is one of the most isolated locations on the planet inhabited by humans. Archaeological and genetic evidence suggests that the island was first colonized by Polynesians around AD 1200, during their eastward expansion. Although it remains contentious whether Polynesians reached South America, suggestive evidence has been brought forward supporting the possibility of Native American contact prior to the European \"discovery\" of the island in AD 1722.', 'We generated genome-wide data for 27 Rapanui. We found a mostly Polynesian ancestry among Rapanui and detected genome-wide patterns consistent with Native American and European admixture. By considering the distribution of local ancestry tracts of eight unrelated Rapanui, we found statistical support for Native American admixture dating to AD 1280-1495 and European admixture dating to AD 1850-1895.",
            "output": [
                "Do genome-wide ancestry patterns in Rapanui suggest pre-European admixture with Native Americans?"
            ]
        },
        {
            "id": "task847-b3af9d207f1948f4932f001172e115b7",
            "input": "Neutrophil gelatinase-associated lipocalin (NGAL) is a novel inflammatory marker that is released from neutrophils. In this study, we evaluated the correlation between serum NGAL level and clinical and angiographic risk scores in patients diagnosed with non-ST elevation acute coronary syndrome (NSTE-ACS).', 'Forty-seven random NSTE-ACS patients and 45 patients with normal coronary arteries (NCA) who underwent coronary angiography were enrolled in the study. GRACE risk score and SYNTAX and Gensini risk scores were used, respectively, for the purpose of clinical risk assessment and angiographic risk scoring. Serum NGAL level was measured via ELISA in peripheral blood samples obtained from the patients at the time of admission.', 'Serum NGAL level was significantly higher in the NSTE-ACS group compared to the control group (112.3\u00b149.6 ng/mL vs. 58.1\u00b124.3 ng/mL, p<0.001). There was a significant positive correlation between serum NGAL levels and the GRACE (r=0.533 and p<0.001), SYNTAX (r=0.395 and p=0.006), and Gensini risk scores (r=0.575 and p<0.001). The intermediate-high SYNTAX (>22) group had statistically significantly higher serum NGAL levels compared to the low SYNTAX (\u226422) group (143\u00b129.5 ng/mL vs. 98.7\u00b143.2 ng/mL, p=0.001).",
            "output": [
                "Are serum neutrophil gelatinase-associated lipocalin levels correlated with the complexity and the severity of atherosclerosis in acute coronary syndrome?"
            ]
        },
        {
            "id": "task847-96ddf1f516c34b248e0f750df9d5572b",
            "input": "Patients suffering traumatic brain and chest wall injuries are often difficult to liberate from the ventilator yet best timing of tracheostomy remains ill-defined. While prior studies have addressed early versus late tracheostomy, they generally suffer from the use of historical controls, which cannot account for variations in management over time. Propensity scoring can be utilized to identify controls from the same patient population, minimizing impact of confounding variables. The purpose of this study was to determine outcomes associated with early versus late tracheostomy by application of propensity scoring.', 'Patients requiring intubation within 48h and receiving tracheostomy from January 2010 to June 2012 were identified. Early tracheostomy (ET) was a tracheostomy performed by the fifth hospital day. ET patients were matched to late tracheostomy patients (LT, tracheostomy after day 5) using propensity scoring and compared for multiple outcomes. Cost for services was calculated using average daily billing rates at our institution.', 'One hundred and six patients were included, 53 each in the ET (mean day tracheostomy=4) and the LT (mean day tracheostomy=10) cohorts. The average age was 47 years and 94% suffered blunt injury, with an average NISS of 23.7. Patients in the ET group had significantly shorter TICU LOS (21.4 days vs. 28.6 days, p<0.0001) and significantly fewer ventilator days (16.7 days vs. 21.9, p<0.0001) compared to the LT group. ET patients also had significantly less VAP (34% vs. 64.2%, p=0.0019).",
            "output": [
                "Does early tracheostomy in trauma patients save time and money?"
            ]
        },
        {
            "id": "task847-f33412532b6e4924b87866c58c4785fe",
            "input": "Prolonged cardiac monitoring detects higher rates of atrial fibrillation (AF) in ischemic stroke and transient ischemic attack (TIA) but is costly and has practical implications. The use of admission troponin-I (TnI) level to identify patients at high risk of delayed AF detection was investigated.', 'Consecutive ischemic stroke and TIA cases presenting to our institute over a 13-month period were identified from the Irish Stroke and TIA Register. Electronic databases and case notes were examined. \"Delayed\" AF was diagnosed after a sinus rhythm admission electrocardiogram and no documented history. Group comparisons were made by AF status. The association between TnI and AF was investigated using a multivariate regression model.', 'A total of 185 cases (130 ischemic stroke) were analyzed. Mean age (standard deviation) was 73.3 (13.9) years, 47% female. Sixty-two cases (33.5%) had AF. The first documented presentation of AF was found in 21 cases, on admission electrocardiogram (n = 11) or inpatient telemetry (delayed, n = 10). TnI was higher in those with delayed AF than in those without AF (W = 194; P = .036). A higher proportion of those with an elevated TnI (30%) than those with a normal TnI (6.1%) had delayed diagnosis of AF (\u03c7(2) = 6.41, P = .011). Having an abnormal TnI was a significant independent predictor of delayed AF detection (odds ratio, 5.8; P = .037).",
            "output": [
                "Is troponin-I a predictor of a delayed diagnosis of atrial fibrillation in acute ischemic stroke and transient ischemic attack?"
            ]
        },
        {
            "id": "task847-2b3d26a0e7614c908f2f5ed61d39c59e",
            "input": "The aim of this study is to investigate the potential effects of borax on ischemia/reperfusion injury of the rat spinal cord.', 'Twenty-one Wistar albino rats were divided into 3 groups: sham (no ischemia/reperfusion), ischemia/reperfusion, and borax (ischemia/reperfusion + borax); each group was consist of 7 animals. Infrarenal aortic cross clamp was applied for 30 minutes to generate spinal cord ischemia. Animals were evaluated functionally with the Basso, Beattie, and Bresnahan scoring system and inclined-plane test. The spinal cord tissue samples were harvested to analyze tissue concentrations of nitric oxide, nitric oxide synthase activity, xanthine oxidase activity, total antioxidant capacity, and total oxidant status and to perform histopathological examination.', 'At the 72nd hour after ischemia, the borax group had significantly higher Basso, Beattie, and Bresnahan and inclined-plane scores than those of ischemia/reperfusion group. Histopathological examination of spinal cord tissues in borax group showed that treatment with borax significantly reduced the degree of spinal cord edema, inflammation, and tissue injury disclosed by light microscopy. Xanthine oxidase activity and total oxidant status levels of the ischemia/reperfusion group were significantly higher than those of the sham and borax groups (P < .05), and total antioxidant capacity levels of borax group were significantly higher than those of the ischemia/reperfusion group (P < .05). There was not a significantly difference between the sham and borax groups in terms of total antioxidant capacity levels (P > .05). The nitric oxide levels and nitric oxide synthase activity of all groups were similar (P > .05).",
            "output": [
                "Does borax partially prevent neurologic disability and oxidative stress in experimental spinal cord ischemia/reperfusion injury?"
            ]
        },
        {
            "id": "task847-094b66f8dde04da3822c3d2f44c3a4a6",
            "input": "Acute kidney injury is a common and serious problem after cardiac surgery. Postoperative acute kidney injury is independently associated with in-hospital mortality and long-term morbidity, even after adjustment for comorbid diseases. Chronic kidney disease has been recognized as a strong risk factor of acute kidney injury after cardiac surgery. The association between proteinuria and postcardiotomy acute kidney injury in patients with preserved glomerular filtration rate remains uncertain.', 'Patients with an estimated glomerular filtration rate greater than 60 mL/min/1.73 m(2) who underwent cardiac surgery between January 2003 and December 2007 in a tertiary medical center were retrospectively analyzed. Dipstick urinalysis was performed before surgery. Proteinuria was categorized into negative, trace, 1+, 2+, or 3+. Postoperative acute kidney injury was defined by the Acute Kidney Injury Network criteria. Multinomial logistic regression was used to clarify whether proteinuria is an independent risk factor of postoperative acute kidney injury.', 'A total of 1246 patients were included in this study, with a mean estimated glomerular filtration rate of 80 \u00b1 13 mL/min/1.73 m(2). Proteinuria was present in 290 patients (23.4%). Postoperative acute kidney injury developed in 434 patients (34.8%), and 36 patients (2.9%) required renal replacement therapy. Proteinuria was independently associated with all stages of postcardiotomy acute kidney injury and dialysis-requiring acute kidney injury. The crude risk of acute kidney injury was greater in patients with a higher grade of proteinuria. In subgroup analysis for gender, diabetes, and surgical type, preoperative proteinuria remains a strong risk factor of acute kidney injury after cardiac surgery.",
            "output": [
                "Does proteinuria predict postcardiotomy acute kidney injury in patients with preserved glomerular filtration rate?"
            ]
        },
        {
            "id": "task847-af1b91cb49154e5c84e83ae199509fc3",
            "input": "To determine whether bowel wall fibrosis can be detected in freshly resected human intestinal specimens based on ultrasound-derived shear wave speed.', \"Seventeen intact (>3-cm) bowel segments (15 small and 2 large intestine) from 12 patients with known or suspected inflammatory bowel disease were procured immediately after surgical resection. Ultrasound shear wave elastography of the bowel wall was performed by two methods (Virtual Touch Quantification [VTQ] and Virtual Touch-IQ [VT-IQ]; Siemens Medical Solutions USA, Inc, Mountain View, CA). Eighteen short-axis shear wave speed measurements were acquired from each specimen: 3 from the 9-, 12-, and 3-o'clock locations for each method. Imaging was performed in two areas for specimens greater than 10 cm in length (separated by \u22655 cm). A gastrointestinal pathologist scored correlative histologic slides for inflammation and fibrosis. Differences in mean shear wave speed between bowel segments with low and high inflammation/fibrosis scores were assessed by a Student t test. Receiver operating characteristic curve analysis was performed.\", 'High-fibrosis score (n = 11) bowel segments had a significantly greater mean shear wave speed than low-fibrosis score (n = 6) bowel segments (mean \u00b1 SD: VTQ, 1.59 \u00b1 0.37 versus 1.18 \u00b1 0.08 m/s; P= .004; VT-IQ, 1.87 \u00b1 0.44 versus 1.50 \u00b1 0.26 m/s; P= .049). There was no significant difference in mean shear wave speed between high-and low-inflammation score bowel segments (P > .05 for both VTQ and VT-IQ). Receiver operating characteristic curves showed areas under the curve of 0.91 (95% confidence interval, 0.67-0.99) for VTQ and 0.77 (95% confidence interval, 0.51-0.94) for VT-IQ in distinguishing low-from high-fibrosis score bowel segments.",
            "output": [
                "Does ultrasound shear wave elastography help discriminate low-grade from high-grade bowel wall fibrosis in ex vivo human intestinal specimens?"
            ]
        },
        {
            "id": "task847-4ccc882615224efba2cd4fe3cbd6d9c0",
            "input": "Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a strong relationship with incident cardiovascular disease (CVD), few studies have examined whether NT-proBNP adds to risk prediction algorithms, particularly in women.', 'This study sought to evaluate the relationship between NT-proBNP and incident CVD in women.', \"Using a prospective case-cohort within the WHI (Women's Health Initiative) observational study, we selected 1,821 incident cases of CVD (746 myocardial infarctions, 754 ischemic strokes, 160 hemorrhagic strokes, and 161 other cardiovascular [CV] deaths) and a randomly selected reference cohort of 1,992 women without CVD at baseline.\", 'Median levels of NT-proBNP were higher at study entry among incident cases (120.3 ng/l [interquartile range (IQR): 68.1 to 219.5 ng/l]) than among control subjects (100.4 ng/l [IQR: 59.7 to 172.6 ng/l]; p\\xa0< 0.0001). Women in the highest quartile of NT-proBNP (\u2265140.8 ng/l) were at 53% increased risk of CVD versus those in the lowest quartile after adjusting for traditional risk factors (1.53 [95% confidence interval (CI): 1.21 to 1.94]; p for trend\\xa0<0.0001). Similar associations were observed after adjustment for Reynolds Risk Score covariables (1.53 [95% CI: 1.20 to 1.95]; p for trend\\xa0<0.0001); the association remained in separate analyses of CV death (2.66 [95% CI: 1.48 to 4.81]; p for trend\\xa0<0.0001), myocardial infarction (1.39\\xa0[95% CI: 1.02 to 1.88]; p for trend\\xa0= 0.008), and stroke (1.60 [95% CI: 1.22 to 2.11]; p for trend\\xa0<0.0001). When added to traditional risk covariables, NT-proBNP improved the c-statistic (0.765 to 0.774; p\\xa0= 0.0003), categorical net reclassification (0.08; p\\xa0< 0.0001), and integrated discrimination (0.0105; p\\xa0<\\xa00.0001). Similar results were observed when NT-proBNP was added to the Reynolds Risk Score.",
            "output": [
                "Do b-type natriuretic peptides improve cardiovascular disease risk prediction in a cohort of women?"
            ]
        },
        {
            "id": "task847-4ede0a7cb97744fa8676887cb7545f58",
            "input": "ADAMTS 13, sP-Selectin and HSP27 have been investigated as potential prognostic markers in patients with hemorrhagic shock.', \"This study was part of a double-blind, randomized, parallel-group, controlled trial and included seventeen trauma patients presented to ED with severe hemorrhagic. The sera for testing were collected from these patients at the time of admission. Investigators and laboratory personnel performing testing were blinded to the patients' identity and clinical course.\", 'The prognostic value of ADAMTS13, sP-Selectin, and HSP27 was compared to prognostic value of systolic blood pressure (SBP), base deficit estimation (BD), heart rate (HR), shock index (SI) and tissue oxygen saturation (StO2) by constructing the receiver operation characteristics (ROC). The area under the curve (AUC) of the ROC for HSP27 (0.92) was greater than for SBP (0.45), BD (0.89), HR (0.61), SI (0.45) and StO2 (0.46). AUC for sP-Selectin (0.86) and for ADAMTS13 antigen (0.74) were comparable with BD one, but greater than for the rest of currently used tests.",
            "output": [
                "Do novel markers predict death and organ failure following hemorrhagic shock?"
            ]
        },
        {
            "id": "task847-9a71b140b74f44b19b54bd3f08500189",
            "input": "The diagnosis of inflammatory bowel disease can be challenging and requires the efforts of a multidisciplinary team. We performed a retrospective analysis with the aim of evaluating the adequacy of the prerequisites for arriving at an accurate histological diagnosis.', 'The following parameters were considered as prerequisites for a diagnosis of inflammatory bowel disease: clinical and endoscopic data; proper sampling and handling of biopsies; and elementary microscopic lesions. We collected 345 cases from 13 centres.', 'The date of onset and treatment were available for 13% and 16% of the cases, respectively. Endoscopy information was accessible for 77% of the cases. Endoscopic mapping was completed in 13% of the cases. In no cases were the biopsies oriented on acetate strips. The diagnosis was conclusive in 47% of the cases. Activity, epithelial disruption and crypt distortion were described in 35% of the reports with a conclusive diagnosis.",
            "output": [
                "Is the diagnosis of inflammatory bowel disease often unsupported in clinical practice?"
            ]
        },
        {
            "id": "task847-f0c9bc5e9945474cb2d2265c855e38a2",
            "input": "Colorectal resection in cirrhotic patients is associated with high mortality and morbidity related to portal hypertension and liver insufficiency.', 'This retrospective study evaluated the clinical outcomes of cirrhotic patients who underwent transjugular intrahepatic porto-systemic shunt (TIPS) placement before colorectal resection for cancer. Main outcomes measures were postoperative morbidity and mortality rates.', 'TIPS placement was successful in all eight patients and significantly decreased the mean hepatic venous pressure gradient from 15.5 \u00b1 2.9 to 7.5 \u00b1 1.9 mmHg (p = 0.02). Surgical procedures included right colectomy (n = 3), left colectomy (n = 2), and proctectomy with total mesorectal excision (n=3). Post-operatively, two patients (25%) died of multiple organ failure. The overall postoperative morbidity rate was 75%, and major complications were seen in 25%.",
            "output": [
                "Does transjugular intrahepatic portosystemic shunt placement increase feasibility of colorectal surgery in cirrhotic patients with severe portal hypertension?"
            ]
        },
        {
            "id": "task847-76f88a019c854e009aca23170283eab0",
            "input": "To evaluate intestinal inflammatory and apoptotic processes after intestinal ischemia/reperfusion injury, modulated by pentoxifylline and hypertonic saline.', 'It was allocated into four groups (n=6), 24 male Wistar rats (200 to 250 g) and submitted to intestinal ischemia for 40 min and reperfusion for 80 min: IR (did not receive any treatment); HS group (Hypertonic Saline, 4 ml/kg-IV); PTX group (Pentoxifylline, 30 mg/kg-IV); HS+PTX group (Hypertonic Saline and Pentoxifylline). All animals were heparinized (100 U/kg). At the end of reperfusion, ileal fragments were removed and stained on hematoxylin-eosin and histochemical studies for COX-2, Bcl-2 and cleaved caspase-3.', 'The values of sO2 were higher on treated groups at 40 minutes of reperfusion (p=0.0081) and 80 minutes of reperfusion (p=0.0072). Serum lactate values were lower on treated groups after 40 minutes of reperfusion (p=0.0003) and 80 minutes of reperfusion (p=0.0098). Morphologic tissue injuries showed higher grades on IR group versus other groups: HS (p=0.0006), PTX (p=0.0433) and HS+PTX (p=0.0040). The histochemical study showed lesser expression of COX-2 (p=0.0015) and Bcl-2 (p=0.0012) on HS+PTX group. A lower expression of cleaved caspase-3 was demonstrated in PTX (p=0.0090; PTXvsIR).",
            "output": [
                "Does pentoxifylline associated to hypertonic saline solution attenuate inflammatory process and apoptosis after intestinal ischemia/reperfusion in rats?"
            ]
        },
        {
            "id": "task847-122f345bedd349039f7b8c017b9a36dc",
            "input": "The aim of this study was to evaluate patterns of the initial recurrence after pancreatectomy for pancreatic cancer and risk factors in each pattern.', 'This study included 209 pancreatic cancer patients who underwent pancreatectomy and of whom the detailed information on the first recurrent lesions detected by imaging during postoperative followup were available. Relapse patterns were classified into 4 groups: liver, peritoneal, local and extra-abdominal recurrences. We evaluated their associations with prognosis and various clinicopathological factors to identify relevant risk factors.', 'Cumulative numbers of patients with liver, peritoneal, local, and extra-abdominal recurrences were 81, 70, 98 and 22, respectively, for the first recurrences. Hepatic relapse was associated with significantly shorter overall survival than other sites (p<0.001) and was an independent prognostic factor in multivariate analysis (p<0.001). Pathological portal vein invasion was the only independent risk factor for hepatic relapse (p=0.045). There was no significant correlation between the depth of invasion and prevalence of hepatic relapse.",
            "output": [
                "Is pattern of first recurrent lesions in pancreatic cancer : hepatic relapse associated with dismal prognosis and portal vein invasion?"
            ]
        },
        {
            "id": "task847-a6b0384fafcd478eb00d0430260c42f4",
            "input": "The novel ACURATE TA\u2122 transcatheter aortic valve (Symetis, Ecublens, Switzerland) is composed of a self-expanding nitinol stent covered by an anti-paravalvular leak skirt designed for transapical implantation. Since Conformite Europeenne (CE)-mark approval, the first 250 patients implanted with the newly approved device have been included in this post-market, multicentre registry.', 'The registry was conducted at 17 sites in Germany, Italy, Switzerland and Argentina to treat 250 high-risk elderly patients. This all-comers population presented preoperatively with a mean aortic gradient of 43.2 \u00b1 17.4 mmHg, mean age of 80.9 \u00b1 6.3 years, mean society of thoracic surgeons risk score of 8.0 \u00b1 5.9% and mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 22.3 \u00b1 12.7%. The majority of patients (93%) were in New York Heart Association (NYHA) class III/IV. All patients were treated within a multidisciplinary Heart Team.', 'The procedural success rate was 98% (n = 245) with two valve-in-valve procedures and three conversions to conventional surgery. The 30-day mortality rate was 6.8%. Postimplant echocardiography revealed a relevant paravalvular leak (moderate 2+) in 2.3% of patients, with all other patients demonstrating either none/trace or a 1+ leak. The 30-day stroke rate was 2.8% and the mean transvalvular gradient was 12.4 \u00b1 5.8 mmHg. A new pacemaker implantation was required in 10.0% of patients and 85% of patients returning for the follow-up presented in NYHA class I/II.",
            "output": [
                "Does first registry result from the newly approved ACURATE TA\u2122 TAVI system\u2020?"
            ]
        },
        {
            "id": "task847-d376d9251de0414bbc3cd37b9087be9a",
            "input": "Gases, such as nitric oxide (NO), carbon monoxide (CO), or hydrogen sulfide (H2S), termed gasotransmitters, play an increasingly important role in understanding of how electrical signaling of cells is modulated. H2S is well-known to act on various ion channels and receptors. In a previous study we reported that H2S increased calcium-activated potassium (BK) channel activity.', 'The goal of the present study is to investigate the modulatory effect of BK channel phosphorylation on the action of H2S on the channel as well as to recalculate and determine the H2S concentrations in aqueous sodium hydrogen sulfide (NaHS) solutions.', 'Single channel recordings of GH3, GH4, and GH4 STREX cells were used to analyze channel open probability, amplitude, and open dwell times. H2S was measured with an anion selective electrode.', 'The concentration of H2S produced from NaHS was recalculated taking pH, temperature salinity of the perfusate, and evaporation of H2S into account. The results indicate that from a concentration of 300 \u03bcM NaHS, only 11-13%, i.e., 34-41 \u03bcM is effective as H2S in solution. GH3, GH4, and GH4 STREX cells respond differently to phosphorylation. BK channel open probability (Po) of all cells lines used was increased by H2S in ATP-containing solutions. PKA prevented the action of H2S on channel Po in GH4 and GH4 STREX, but not in GH3 cells. H2S, high significantly increased Po of all PKG pretreated cells. In the presence of PKC, which lowers channel activity, H2S increased channel Po of GH4 and GH4 STREX, but not those of GH3 cells. H2S increased open dwell times of GH3 cells in the absence of ATP significantly. A significant increase of dwell times with H2S was also observed in the presence of okadaic acid.",
            "output": [
                "Does phosphorylation of BK channels modulate the sensitivity to hydrogen sulfide ( H2S )?"
            ]
        },
        {
            "id": "task847-4e8395be5359445e911a45442de4c691",
            "input": "Covert hepatic encephalopathy (CHE) is associated with cognitive dysfunction, which affects daily function and health-related quality of life (HRQOL) in patients with cirrhosis. The effects of CHE and liver disease are determined by cognitive reserve\u2014the ability of the brain to cope with increasing damage while continuing to function\u2014and are assessed by composite intelligence quotient (IQ) scores. We examined cognitive reserve as a determinant of HRQOL in patients with cirrhosis.', 'We performed a prospective study of 118 outpatients with cirrhosis without overt HE (age, 56 y). We studied cognition using the standard paper-pencil battery; patients with below-normal results for more than 2 tests were considered to have CHE. We also assessed HRQOL (using the sickness impact profile [SIP]), psychosocial and physical scores (a high score indicates reduced HRQOL), model for end-stage liver disease (MELD) scores, and cognitive reserve (using the Barona Index, a validated IQ analysis, based on age, race, education, residence area, and occupation). Cognitive reserve was divided into average and high groups (<109 or >109), and MELD and SIP scores were compared. We performed regression analyses, using total SIP score and psychosocial and physical dimensions as outcomes, with cognitive reserve, CHE, and MELD score as predictors.', 'Study participants had average MELD scores of 9, and 14 years of education; 81% were white, 63% were urban residents, their mean IQ was 108 \u00b1 8, and 54% had average cognitive reserve (the remaining 46% had high reserves). CHE was diagnosed in 49% of patients. Cognitive reserve was lower in patients with CHE (109) than without (105; P = .02). Cognitive reserve correlated with total SIP and psychosocial score (both r = -0.4; P < .001) and physical score (r = -0.3; P = .01), but not MELD score (P = .8). Patients with high cognitive reserve had a better HRQOL, despite similar MELD scores. In regression analyses, cognitive reserve was a significant predictor of total SIP (P < .001), psychosocial (P < .001), and physical scores (P < .03), independent of CHE, MELD, or psychiatric disorders.",
            "output": [
                "Is cognitive reserve a determinant of health-related quality of life in patients with cirrhosis , independent of covert hepatic encephalopathy and model for end-stage liver disease score?"
            ]
        },
        {
            "id": "task847-6ac8f5c7cb92470cb6fe845fcd7fe143",
            "input": "Sarcoidosis is a multisystem disease of unknown origin. Determining the involvement and the response to the treatment is important. The aim of this study was to identify the effects of methylprednisolone and indomethacine on metabolic activity and pulmonary function test parameters in patients with sarcoidosis.', 'A total of 24 pulmonary sarcoidosis patients were enrolled in the study. All the patients underwent spirometry and [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan before treatment and were divided into two groups according to the necessity of corticosteroid treatment or not. Patients who did not have corticosteroid indication were treated with indomethacine. Symptomatic patients and patients who did not respond to indomethacine treatment received methylprednisolone. Patients were followed up on a monthly basis to determine the response. FDG uptakes as the disease activity were re-evaluated before ending the treatment at the sixth month.', 'Mean age of patients (16 male, 8 female) was 39.79 (9.3) years. Besides mediastinum and pulmonary parenchyma, extrapulmonary sites were also involved in patients with pulmonary sarcoidosis (distant lymph nodes (upper abdominal, supraclavicular, inguinal, and axillary), liver, and spleen). Although maximum standard uptake values of methylprednisolone group regressed significantly (p\\u2009<\\u20090.001) after treatment, indomethacine group did not have significant regression (p\\u2009=\\u20090.345). Despite metabolic regressions, spirometry values of patients did not significantly increase (p\\u2009>\\u20090.005).",
            "output": [
                "Does use of PET-CT for the assessment of treatment result in patients with sarcoidosis?"
            ]
        },
        {
            "id": "task847-e6e193321e1c4908bbcaef0500e13ffc",
            "input": "Aerobic exercise can decrease postprandial triglyceride (TG) concentrations but the relationship between exercise-induced energy deficits and postprandial lipemia is still unclear. The aim of the present study was to examine the effect of a single bout of aerobic exercise, with and without energy replacement, on postprandial lipemia and on peripheral blood mononuclear cell (PBMC) mRNA expression of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) receptors and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR).', 'Nine healthy male humans completed three two-day trials in a random order. On day 1, volunteers rested (CON), completed 60 minutes of treadmill walking at 50% of VO2peak (EX) or completed the same bout of walking but with the energy replaced afterwards with a glucose solution (EXG). On day 2, volunteers rested and consumed a high fat test meal in the morning.', 'Total and incremental TG AUC were significantly lower on the EXG (P\\u2009<\\u20090.05) and EX (P\\u2009<\\u20090.05) trials than the CON trial with no difference between the two exercise trials. No significant difference was observed in VLDL or LDL receptor mRNA expression among the trials (P\\u2009>\\u20090.05).",
            "output": [
                "Does energy replacement using glucose increase postprandial lipemia after moderate intensity exercise?"
            ]
        },
        {
            "id": "task847-fdbf5984ad17432cb1e828f9594ce01f",
            "input": "This study was to examine the association between plasma retinol binding protein 4 (RBP4) levels and the complexity of angiographic coronary lesion in patients with coronary artery disease (CAD).', 'A cross-sectional and prospective study was carried out in Guangzhou Chinese population. 672 persons were evaluated by medical history, clinical examination, coronary angiography, and fasting plasma samples, and were followed prospectively for 3 years. We measured the plasma RBP4 levels in 447 women (201 with stable CAD and 246 with acute coronary syndrome [ACS]). Coronary lesions were classified as having a simple or complex appearance based on the visual estimation of the coronary angiograms. Median plasma RBP4 levels were significantly higher in stable CAD patients with complex coronary lesions (n\\xa0=\\xa084) than in those with simple lesions (n\\xa0=\\xa0117) (38.78[range 32.65-46.91] vs. 30.78 [range 24.48-36.08] \u03bcg/ml, P\\xa0<\\xa00.001). Multiple logistic regression analysis demonstrated that higher RBP4 levels were independently associated with a 23% higher risk for complex lesions (odds ratio 1.228, 95% confidence interval [CI] 1.061 to 1.358; P\\xa0=\\xa00.031). Among the ACS patients, who had higher RBP4 levels than the stable CAD patients, those with multiple complex lesions had significantly higher median RBP4 levels than those with a single complex lesion (46.47\\xa0\u03bcg/ml [range 37.68-53.29] vs. 38.15\\xa0\u03bcg/ml [range 32.26-44.56], P\\xa0<\\xa00.001). Total plasma RBP4 levels were predictors of cardiac death (hazard ratio [HR]: 1.102; 95% CI: 1.086 to 1.191; P\\xa0=\\xa00.012) after adjustment for traditional risk factors for CAD.",
            "output": [
                "Is circulating retinol binding protein 4 associated with coronary lesion severity of patients with coronary artery disease?"
            ]
        },
        {
            "id": "task847-43169e1e31b24be08915a433750a19da",
            "input": "To examine if overall diet quality is associated with cellular and soluble biomarkers of systemic inflammation in middle-aged individuals.', 'A group of 667 individuals, aged 63-68 years, selected from the cardiovascular arm of the Malm\u00f6 Diet and Cancer cohort, participated in this study. Baseline examinations consisted of an extensive socio-demographic questionnaire, anthropometric measurements, blood sampling and detailed dietary data. Mononuclear leukocytes frozen at baseline were thawed and analysed with flow cytometry to quantify monocyte subsets based on CD14 and CD16 expression. Plasma cytokines were measured using multiplexed immune assays. A diet quality index consisting of six components (saturated fatty acids, polyunsaturated fatty acids, fish and shellfish, dietary fibre, fruit and vegetables, and sucrose) was constructed to measure adherence to the Swedish Nutrition Recommendations/Dietary Guidelines. General linear models were used to investigate associations between index scores and several biomarkers of inflammation.', 'A higher percentage of women reported adherence to the nutritional recommendations and had better overall diet quality than men. Participants with higher diet quality were more likely to have a healthier lifestyle. The levels of high-sensitive CRP, S100A8/A9, TNF-\u03b1, white blood cells, neutrophils, lymphocytes and CD14(+)CD16(++) were lower in participants with higher index scores. The associations remained significant after adjustment for potential confounders.",
            "output": [
                "Is a high quality diet associated with reduced systemic inflammation in middle-aged individuals?"
            ]
        },
        {
            "id": "task847-e298337fb6eb4570ae8f24b03f6bb1d0",
            "input": "Due to recent war situation in neighboring country we have witnessed large number of victims with post-traumatic false (pseudo) aneurysms of head and neck in roadside bomb blast victims in Pakistan. Thus through this observational retrospective study we aim to share our experience of managing these patients.', \"5 years patients' case records, from June 2008-June 2013, were reviewed from the hospital's records. 14 cases of roadside bomb blast victims, developing false aneurysms of major or minor vessels of head and neck, were studied. We excluded the post-traumatic pseudoaneurysms involving other sites and vessels of the body. We observed the mechanism, the duration of presentation, symptoms/signs, vessels involved, complications and the management done.\", 'All 14 cases presented with a localized pulsatile swelling with tenderness in the course of a known artery and with an overlying entry site wound from bomb blast sharp nails. Men were affected more as compared to women. All (14) cases had 2-12 weeks of duration between the injury and presentation. Temporal artery (4) was involved in most cases followed by common carotid artery (3). Open surgery was treatment of choice in 12 (85.7%) of cases; however 2 (14.3%) patients had endovascular intervention to correct the pathology. Post-operatively all patients recovered completely, without any major or minor complications.",
            "output": [
                "Does pseudoaneurysm of head and neck vessels have been frequently observed in road side bomb blast victims?"
            ]
        },
        {
            "id": "task847-a22cccc8b3714079a646577051ee6699",
            "input": "Vulvovaginitis has a known association with urinary tract infections (UTIs) in girls. We hypothesize that vulvovaginitis is a major contributor to UTIs in prepubertal girls by increasing periurethral colonization with uropathogens.', 'Periurethral swabs and urine specimens were obtained from a total of 101 girls (58 with vulvovaginitis and 43 without vulvovaginitis). Specimens were cultured for bacterial growth. The dominant organism in the periurethral swabs and urine cultures was recorded and antibiotic sensitivity profiles were compared.', 'Periurethral swabs from children with vulvovaginitis were associated with a statistically significant increase in uropathogenic bacteria (79% Enterococcus species or Escherichia coli) as the dominant culture compared with swabs from girls without vaginitis (18%) (p\\u2009<\\u20090.05). In children with vulvovaginitis, 52% of the urine cultures were positive for UTIs, and the dominant organism in the urine cultures matched the species and antibiotic sensitivity profile of the corresponding periurethral swab. Only 11% of the urine cultures from girls without vulvovaginitis were positive for UTIs.",
            "output": [
                "Is altered perineal microbiome associated with vulvovaginitis and urinary tract infection in preadolescent girls?"
            ]
        },
        {
            "id": "task847-09761c5df3ee43f2aaf52090a9558c78",
            "input": "Stroke is a leading cause of disability. However, there is no pharmacological therapy available for promoting recovery. Although treatment of stroke with cystamine has gained increasing interest, the detailed mechanisms underlying this process remain elusive. Thus, our aim is to examine the effect of cystamine on the function recovery after stroke and investigate further cystamine mechanisms.', 'Adult male C57BL/6J mice were subjected to photothrombotic model of focal stroke or sham operation. Cystamine or saline was administered intraperitoneally at 24\\xa0h after stroke. Functional recovery was analyzed using behavioral tests; axon remodeling was analyzed using magnetic resonance diffusion tensor imaging (DTI) and histological assessment. ANA-12, an antagonist of tropomyosin-related kinase B (TrkB), was administrated to examine the mechanisms underlying the neuroprotection mediated by cystamine.', 'Treatment with cystamine resulted in amelioration of impaired function with concomitant enhancement of axonal remodeling. Cystamine treatment significantly increased brain-derived neurotrophic factor (BDNF) levels and phosphorylation of TrkB in brain after stroke. Cystamine significantly enhanced neuronal progenitor cell proliferation, neuronal survival, and plasticity through BDNF/TrkB pathway.",
            "output": [
                "Does cystamine improve functional recovery via axon remodeling and neuroprotection after stroke in mice?"
            ]
        },
        {
            "id": "task847-e648fbf2e1444157b330ca84de075726",
            "input": "Antibody resistance, not only de novo but also acquired cases, usually exists and is related with lower survival rate and high risk of recurrence. Reversing the resistance often results in better clinical therapeutic effect. Previously, we established a trastuzumab-resistant ovarian cancer cell line, named as SKOV3-T, with lower HER2 and induced higher IGF-1R expression level to keep cell survival.', 'IGF-1R was identified important for SKOV3-T growth. Then, a novel anti-IGF-1R monoclonal antibody, named as LMAb1, was used to inhibit SKOV3-T in cell growth/proliferation, migration, clone formation and in vivo carcinogenicity.', 'In both in vitro and in vivo assays, LMAb1 showed effective anti-tumor function, especially when being used in combination with trastuzumab, which was beneficial to longer survival time of mice as well as smaller tumor. It was also confirmed preliminarily that the mechanism of antibody might be to inhibit the activation of IGF-1R and downstream MAPK, AKT pathway transduction.",
            "output": [
                "Does anti-IGF-1R monoclonal antibody inhibit the carcinogenicity activity of acquired trastuzumab-resistant SKOV3?"
            ]
        },
        {
            "id": "task847-3facc5a337544466aa539f41af608c7c",
            "input": "The failing heart displays increased glycolytic flux that is not matched by a commensurate increase in glucose oxidation. This mismatch induces increased anaplerotic flux and inefficient glucose metabolism. We previously found adult transgenic mouse hearts expressing the fetal troponin I isoform, (ssTnI) to be protected from ischemia by increased glycolysis. In this study, we investigated the metabolic response of adult mouse hearts expressing ssTnI to chronic pressure overload.', 'At 2 to 3 months of age, ssTnI mice or their nontransgenic littermates underwent aortic constriction (TAC). TAC induced a 25% increase in nontransgenic heart size but only a 7% increase in ssTnI hearts (P<0.05). Nontransgenic TAC developed diastolic dysfunction (65% increase in E/A ratio), whereas the E/A ratio actually decreased in ssTnI TAC. Isolated perfused hearts from nontransgenic TAC mice showed reduced cardiac function and reduced creatine phosphate:ATP (16% reduction), but ssTnI TAC hearts maintained cardiac function and energy charge. Contrasting nontransgenic TAC, ssTnI TAC significantly increased glucose oxidation at the expense of palmitate oxidation, preventing the increase in anaplerosis observed in nontransgenic TAC hearts. Elevated glucose oxidation was mediated by a reduction in pyruvate dehydrogenase kinase 4 expression, enabling pyruvate dehydrogenase to compete against anaplerotic enzymes for pyruvate carboxylation.",
            "output": [
                "Does metabolic efficiency promote protection from pressure overload in hearts expressing slow skeletal troponin I?"
            ]
        },
        {
            "id": "task847-8cdfa1dc071f4877810d78503df2915d",
            "input": "To investigate the role of preoperative neutrophil-to-lymphocyte ratio (NLR) in prediction of response to first-line platinum-based chemotherapy and survival outcome in serous ovarian cancer (SOC) patients.', 'Clinicopathologic data were reviewed for patients with SOC treated with primary cytoreduction followed by platinum-based chemotherapy. The correlations of NLR value with clinicopathological features, clinical response to chemotherapy, and survival outcome were further explored.', 'High preoperative NLR was significantly associated with advanced FIGO stage, histological grade, increased serum CA-125 level, and positive lymph node metastasis (P < 0.05, respectively). SOC patients in the third and fourth NLR quartile had significantly lower complete response rates compared to those in the first NLR quartile. In addition, survival analysis identified NLR as an independent prognostic factor for both PFS (HR 2.262, 95% CI 1.342-3.811; P = 0.002) and OS (HR 3.254, 95% CI 1.741-6.084; P < 0.001) in SOC patients.",
            "output": [
                "Does preoperative neutrophil-to-lymphocyte ratio predict response to first-line platinum-based chemotherapy and prognosis in serous ovarian cancer?"
            ]
        },
        {
            "id": "task847-79e8e172b6004feba1ae85637b19c67f",
            "input": "Young adults are a population at great risk for problematic health behaviors. Alcohol mixed with energy drink (AmED) consumption is a relatively popular health risk behavior among young adults. AmED consumption continues to illustrate negative outcomes in the research literature, having been linked with other substance use, high-risk sexual behavior, and sexual victimization. Limited research to date has examined associations between AmED consumption and patterns of alcohol dependence.', 'Undergraduate college students (n=757) filled out an online survey which assessed their drinking habits in the past week and month, including their consumption of AmED beverages, personality characteristics, substance use, and problematic alcohol consumption via the Alcohol Use Disorders Identification Test (AUDIT).', 'A minority of participants reported AmED consumption in both the past month (11.6%) and past week (9.7%). Compared to their alcohol-only drinking counterparts, AmED consumers scored significantly higher on measures of impulsivity, and lower on anxiety sensitivity when compared to their alcohol-only drinking counterparts. In multivariate analyses, AmED consumption was robustly associated with patterns of alcohol dependence (AUDIT score\u22658) among young adult college students, while controlling for energy drink use, alcohol use, personality factors, substance use, and demographic variables.",
            "output": [
                "Are alcohol mixed with energy drinks robustly associated with patterns of problematic alcohol consumption among young adult college students?"
            ]
        },
        {
            "id": "task847-775bea9b4d0b452ab0cb5396b0802a0a",
            "input": "Physical inactivity has been associated with obesity and related chronic diseases. Understanding built environment (BE) influences on specific domains of physical activity (PA) around homes and workplaces is important for public health interventions to increase population PA.', 'To examine the association of home and workplace BE features with PA occurring across specific life domains (work, leisure, and travel).', 'Between 2012 and 2013, telephone interviews were conducted with participants in four Missouri metropolitan areas. Questions included sociodemographic characteristics, home and workplace supports for PA, and dietary behaviors. Data analysis was conducted in 2013; logistic regression was used to examine associations between BE features and domain-specific PA.', \"In home neighborhoods, seven of 12 BE features (availability of fruits and vegetables, presence of shops and stores, bike facilities, recreation facilities, crime rate, seeing others active, and interesting things) were associated with leisure PA. The global average score of home neighborhood BE features was associated with greater odds of travel PA (AOR=1.99, 95% CI=1.46, 2.72); leisure PA (AOR=1.84, 95% CI=1.44, 2.34); and total PA (AOR=1.41, 95% CI=1.04, 1.92). Associations between workplace neighborhoods' BE features and workplace PA were small but in the expected direction.",
            "output": [
                "Does home and workplace built environment support for physical activity?"
            ]
        },
        {
            "id": "task847-e0628adaa6034ede9255c3582d1fb0ff",
            "input": "Parenting practices can reduce how much television (TV) children watch. This study evaluated the longitudinal association between maternal regulation of TV content and the amount of TV watched by low-income ethnic minority children.', 'This was a secondary data analysis of the Welfare, Children & Families: A Three City Study. Data were used from ethnic minority mothers with a child from birth to 4 years old, collected over two waves approximately 16 months apart. The dependent variable was the amount of TV watched by the child (wave two). The main independent variable was the maternal regulation of TV content (wave one). Using multiple linear regression, we evaluated the relationship between maternal regulation of TV content and the amount of TV watched by the child, adjusting for covariates.', 'Of the 835 mothers, 71% were high content regulators and 8% reported no content regulation. Children whose mothers reported no regulation watched more TV approximately 16 months later than those whose mothers reported high regulation of content (\u03b2 = 0.91, 95% CI: 0.09-1.73).",
            "output": [
                "Do young low-income ethnic minority children watch less television when their mothers regulate what they are viewing?"
            ]
        },
        {
            "id": "task847-e22af19a201f4511bbde2ccd82abcbef",
            "input": "To determine the clinically recognizable error rate with the use of quantitative polymerase chain reaction (qPCR)-based comprehensive chromosomal screening (CCS).', 'Retrospective study.', 'Multiple fertility centers.', 'All patients receiving euploid designated embryos.', 'Trophectoderm biopsy for CCS.', 'Evaluation of the pregnancy outcomes following the transfer of qPCR-designated euploid embryos. Calculation of the clinically recognizable error rate.', 'A total of 3,168 transfers led to 2,354 pregnancies (74.3%). Of 4,794 CCS euploid embryos transferred, 2,976 gestational sacs developed, reflecting a clinical implantation rate of 62.1%. In the cases where a miscarriage occurred and products of conception were available for analysis, ten were ultimately found to be aneuploid. Seven were identified in the products of conception following clinical losses and three in ongoing pregnancies. The clinically recognizable error rate per embryo designated as euploid was 0.21% (95% confidence interval [CI] 0.10-0.37). The clinically recognizable error rate per transfer was 0.32% (95% CI 0.16-0.56). The clinically recognizable error rate per ongoing pregnancy was 0.13% (95% CI 0.03-0.37). Three products of conception from aneuploid losses were available to the molecular laboratory for detailed examination, and all of them demonstrated fetal mosaicism.",
            "output": [
                "Is clinically recognizable error rate after the transfer of comprehensive chromosomal screened euploid embryos low?"
            ]
        },
        {
            "id": "task847-f47c1273af2d4f60947dfcbb9c6974b6",
            "input": "Aging and obesity are associated with elevated pro-inflammatory cytokines such as monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)\u03b1, which are linked to insulin resistance. Anti-inflammatory agents have marginal effect in improving insulin resistance. Hence, agents are needed to improve glycemic control despite the inflammation. Ad36, a human adenovirus, increases TNF\u03b1 and MCP1 mRNA in adipose tissue, yet improves glycemic control in mice. Ad36 via its E4orf1 gene, up-regulates AKT/glucose transporter (Glut)-4 signaling to enhance cellular glucose uptake.', 'Directly test a role of Ad36, or E4orf1 in enhancing cellular glucose uptake in presence of inflammatory cytokines.', 'Experiment 1: 3T3-L1 preadipocytes were treated with 0, 10 or 100\\xa0ng/mL lipopolysaccharides (LPS), and infected with 0 or 5 plaque forming units (PFU) of Ad36/cell. 3T3-L1 cells that stably and inducibly express E4orf1 or a null vector (pTRE-E4orf1 or pTRE-null cells), were similarly treated with LPS and then with doxycycline, to induce E4orf1. Experiment 2: 3T3L1 preadipocytes were treated with 25\\xa0nM MCP1 or 20\\xa0nM TNF\u03b1 for 16\\xa0h, followed by infection with 0 or 5\\xa0PFU of Ad36/cell. Experiment 3: pTRE-E4orf1 or -null cells were similarly treated with MCP1 or TNF\u03b1 followed by doxycycline to induce E4orf1. Cellular glucose uptake and cellular signaling were determined 72\\xa0h post-Ad36 infection or E4orf1-induction, in continued presence of MCP1 or TNF\u03b1.', 'In 3T3-L1 preadipocytes, Ad36, but not E4orf1, increased MCP1 and TNF\u03b1 mRNA, in presence of LPS stimulation. Ad36 or E4orf1 up-regulated AKT-phosphorylation and Glut4 and increased glucose uptake (P\\xa0<\\xa00.05) in the presence of MCP1 or TNF\u03b1.",
            "output": [
                "Do human adenovirus Ad36 and its E4orf1 gene enhance cellular glucose uptake even in the presence of inflammatory cytokines?"
            ]
        },
        {
            "id": "task847-c667c2e23b984c23a342368e3f0b4737",
            "input": "The aim of this study was to evaluate the characteristics of low-energy femoral insufficiency fractures in elderly patients.', 'The study retrospectively evaluated the clinical course of 4 patients with low-energy femoral shaft and subtrochanteric fractures admitted to our department between 2009 and 2011. Three patients had prior long-term alendronate therapy and one had prior glucocorticoid therapy.', 'There were 5 femoral shaft fractures, 2 incomplete shaft fractures, 2 subtrochanteric and 1 intertrochanteric fractures. All femoral shaft fractures had characteristic fracture patterns with thickened lateral cortices at the proximal fragment. Six femurs had excessive medial femoral bowing, which complicated intramedullary nailing. Additional fractures were seen on both femurs of one patient who had been primarily treated with short implants. A bifocal femoral fracture was seen in one femur. Union was achieved in all patients. Two patients were able to walk independently, one with a cane and one with double crutches.",
            "output": [
                "Does femoral insufficiency fractures in the elderly - excessive medial femoral bowing complicate intramedullary nailing?"
            ]
        },
        {
            "id": "task847-d7bd5f2e34794ee89814da84e98b7309",
            "input": "Mutation of Arabidopsis DMR1, encoding homoserine kinase, leads to elevation in homoserine and foliar resistance to the biotrophic pathogens Hyaloperonospora arabidopsidis and Oidium neolycopersici through activation of an unidentified defence mechanism. This study investigates the effect of mutation of dmr1 on resistance to the ascomycete pathogens Fusarium graminearum and F. culmorum, which cause Fusarium Ear Blight (FEB) disease on small grain cereals.', 'We initially found that the dmr1-2 mutant allele confers increased resistance to F. culmorum and F. graminearum silique infection, and decreased colonisation of rosette leaves. Meanwhile the dmr1-1 allele supports less rosette leaf colonisation but has wild type silique resistance. Three additional dmr1 alleles were subsequently examined for altered F. culmorum susceptibility and all showed increased silique resistance, while leaf colonisation was reduced in two (dmr1-3 and dmr1-4). Amino acid analysis of dmr1 siliques revealed homoserine accumulation, which is undetectable in wild type plants. Exogenous application of L-homoserine reduced bud infection in both dmr1 and wild type plants, whilst D-homoserine application did not. Delayed leaf senescence was also observed in dmr1 plants compared to wild type and correlated with reduced Fusarium leaf colonisation.",
            "output": [
                "Do mutations in the Arabidopsis homoserine kinase gene DMR1 confer enhanced resistance to Fusarium culmorum and F. graminearum?"
            ]
        },
        {
            "id": "task847-6be1f895a24542efa6ee5d0210ffc470",
            "input": "To investigate the relationship between tissue elasticity before and after antiviral therapy and shear wave as well as strain elastography.', 'FibroScan and real-time tissue elastography were performed before and after antiviral therapy for chronic hepatitis C, and treatment efficacy and elastographic findings were comparatively analyzed. Elasticity was evaluated by measuring liver stiffness (LS) in kilopascals using FibroScan, and the liver fibrosis index (LFI) was assessed by real-time tissue elastography.', 'LS and LFI correlated well before and after therapy (r = 0.567, p = 0.003 and r = 0.576, p = 0.002, respectively). In the group without a sustained virological response (SVR), LS increased in 4 of 5 patients. Patients with an increase in both LS and LFI were all in the non-SVR group (3/3, 100%). In addition, LS increased in all patients except 1 in the non-SVR group (4/5, 80%). In the SVR group, both LS and LFI decreased in all patients except 1 (18/19, 94.7%). In the patient with an increase in LS despite achieving SVR, LS decreased quickly after alcohol cessation.",
            "output": [
                "Does ultrasound elastography correlate treatment response by antiviral therapy in patients with chronic hepatitis C?"
            ]
        },
        {
            "id": "task847-6969e25f5ab84fa2a700212d605ac707",
            "input": "The timing of CEA for symptomatic internal carotid artery (ICA) stenosis remains a matter of controversy. Recent registry data showed a significantly increased risk, especially in the very early days after the onset of symptoms. In this study the outcome of CEA in the hyperacute phase has been investigated.', 'The outcome of CEA for symptomatic ICA stenosis between January 2004 and December 2013 has been retrospectively analyzed. Patients were divided into four timing groups: surgery within 0 and 2 days, between 3 and 7 days, 8 and 14 days, and thereafter. The post-operative 30 day stroke and death rates were assessed.', 'A total of 761 symptomatic patients (40.1% with transient ischemic attack [TIA], 21.3% with amaurosis fugax, and 38.6% with ischemic stroke) were included, with an overall peri-operative stroke and death rate of 3.3%. A stroke and death rate of 4.4% (9/206) for surgery within 0 and 2 days, 1.8% (4/219) between 3 and 7 days, 4.4% (6/136) between 8 and 14 days, and 2.5% (5/200) in the period thereafter (p\\xa0=\\xa0.25 for the difference between the groups) was observed. The timing of surgery did not influence the peri-operative outcome in a multivariate regression analysis (OR 0.93 [0.63-1.36], p\\xa0=\\xa0.71).",
            "output": [
                "Does very urgent carotid endarterectomy increase the procedural risk?"
            ]
        },
        {
            "id": "task847-8413b31f46e2402897bd984c9c282520",
            "input": "To investigate B7-H4 expression and its correlation with the number of infiltrating T lymphocytes and cytokine production by those lymphocytes in human cervical cancer and to determine the effect of recombinant B7-H4 on the active peripheral blood T cells of the patients in vitro.', 'B7-H4 expression was detected in 67 cases of cervical cancer using immunohistochemical staining. Tumor-infiltrating CD8(+)T, CD4(+)T, and FOXP3(+) (Forkhead Box P3) T lymphocytes and their levels of IFN-\u03b3 and TGF-\u03b2\u2081 production were determined by immunofluorescent double-staining. After the peripheral blood T lymphocytes of patients were co-cultured with B7-H4, proliferation, apoptosis, and cell subtypes were analyzed using flow cytometry. Cytokines in the supernatant were detected by ELISA.', \"B7-H4 was expressed in 46% (31/67) of the cases of cervical cancer. The number of infiltrating CD8(+)T lymphocytes and their IFN-\u03b3 production in positive B7-H4 expression cervical cancers was significantly lower than in negative B7-H4 cases (P<0.01, P<0.05), but there was no significant difference between cases positive and negative for B7-H4 with respect to infiltrating FOXP3(+)T and CD4(+)T cells or TGF-\u03b21 production. After co-culture with B7-H4 for 48 h, the patients' activated T lymphocytes were arrested at G1/G2 phase. The Ki67 positive rates of CD4(+)T and CD8(+)T cells were 2.13 \u00b1 0.13% and 1.03 \u00b1 1.33%, and they were lower than in the blank group. The proportion of CD4(+)T and CD8(+)T cells decreased, but CD4(+)T/CD8(+)T and the proportion of CD4(+)CD25(+)Foxp3(+)T cells increased. In addition, concentrations of IL-10 and TGF-\u03b21 in the supernatant of co-cultured T cells increased significantly (P<0.05, P<0.05), but that of IFN-\u03b3 decreased. B7-H4 had no significant effect on apoptosis of the T cells.",
            "output": [
                "Does b7-H4 overexpression impair the immune response of T cells in human cervical carcinomas?"
            ]
        },
        {
            "id": "task847-3fa9bba811fd4084aaf2c8d3466fa1e7",
            "input": "To evaluate the staging accuracy of preoperative multiparametric MRI (mp-MRI), its influence on the technique of radical retropubic prostatectomy (RRP), and its value for daily clinical practice.', 'A total of 106 patients underwent RRP (January 2011-June 2012) and had preoperative MRI staging data available for review. Staging results acquired by mp-MRI were correlated to both biopsy and histopathology results. Surgical reports were reviewed for intraoperative aspect of tumor extension, technique of RRP (nerve sparing or extended), and extent of lymphadenectomy.', 'The accuracy of diagnosing extracapsular extension (ECE) was 72.2 %, with an overall sensitivity and specificity of 30.0 and 93.3 %, respectively. The negative predictive value was 72.7 %. The sensitivity and specificity to diagnose positive seminal vesical invasion (SVI) were 63.6 and 92.9 %, respectively. Neither higher field force nor the use of an endorectal coil could enhance the accuracy of mp-MRI. In case of awareness of an existing MRI, there was a significantly higher percentage of nerve protection (left: 93 %; right: 89 % vs. left 75 %; right: 75 %). The higher percentage of nerve sparing surgery did not result in a higher level of positive resection margins.",
            "output": [
                "Does preoperative mp-MRI of the prostate provide little information about staging of prostate carcinoma in daily clinical practice?"
            ]
        },
        {
            "id": "task847-9504b88879a54914b91457070fda3fd8",
            "input": "Brassica napus (AACC) is self-compatible, although its ancestor species Brassica rapa (AA) and Brassica oleracea (CC) are self-incompatible. Most B.napus accessions have dominant self-compatibility (SC) resulting from an insertion of 3.6 kb in the promoter region of BnSCR-1 on the A genome, while recessive SC in B.napus has rarely been observed. Expression and cloning of SRK and SCR genes and genetic analysis were carried out to dissect bases of recessive SC in B.napus.', 'Eleven accessions were screened to identify stable recessive SC and had the S genotype BnS-7 on the A genome and BnS-6 on the C genome similarly to BrS-29 and BoS-15, respectively. In eight SC accessions, BnSCR-7 and BnSCR-6 were nearly undetectable and harbored no structural mutations in the promoters, while SRK genes were expressed at normal levels and contained intact CDS, with the exception of BnSRK-7 in line C32. SRK and SCR genes were expressed normally but their CDSs had no mutations in three SC accessions. In self-incompatible S-1300 and 11 F1 hybrids, SRK genes and BnSCR-1300 transcripts were present at high levels, while expression of the BnSCR-7 and BnSCR-6 were absent. Plants of S genotype S1300S1300 were completely SI, while SI phenotypes of SBnS-7SBnS-7 and S1300SBnS-7 plants were segregated in BC1 and F2 populations.",
            "output": [
                "Do gene expression and genetic analysis reveal diverse causes of recessive self-compatibility in Brassica napus L?"
            ]
        },
        {
            "id": "task847-4b9adc91b17342a89df245706c4f80a7",
            "input": "Prostaglandin D2 (PGD2) and cysteinyl leukotrienes (cysLTs) are lipid mediators derived from mast cells, which activate TH2 cells. The combination of PGD2 and cysLTs (notably cysteinyl leukotriene E4 [LTE4]) enhances TH2 cytokine production. However, the synergistic interaction of cysLTs with PGD2 in promoting TH2 cell activation is still poorly understood. The receptors for these mediators are drug targets in the treatment of allergic diseases, and hence understanding their interaction is likely to have clinical implications.', 'We aimed to comprehensively define the roles of PGD2, LTE4, and their combination in activating human TH2 cells and how such activation might allow the TH2 cells to engage downstream effectors, such as neutrophils, which contribute to the pathology of allergic responses.', 'The effects of PGD2, LTE4, and their combination on human TH2 cell gene expression were defined by using a microarray, and changes in specific inflammatory pathways were confirmed by means of PCR array, quantitative RT-PCR, ELISA, Luminex, flow cytometry, and functional assays, including analysis of downstream neutrophil activation. Blockade of PGD2 and LTE4 was tested by using TM30089, an antagonist of chemoattractant receptor-homologous molecule expressed on TH2 cells, and montelukast, an antagonist of cysteinyl leukotriene receptor 1.', 'PGD2 and LTE4 altered the transcription of a wide range of genes and induced diverse functional responses in TH2 cells, including cell adhesion, migration, and survival and cytokine production. The combination of these lipids synergistically or additively enhanced TH2 responses and, strikingly, induced marked production of diverse nonclassical TH2 inflammatory mediators, including IL-22, IL-8, and GM-CSF, at concentrations sufficient to affect neutrophil activation.",
            "output": [
                "Do prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk?"
            ]
        },
        {
            "id": "task847-4664dda4fdac4a04ba82fa1f2e9876f3",
            "input": "Breast-feeding is protective against respiratory infections in early life. Given the co-evolutionary adaptations of humans and cattle, bovine milk might exert similar anti-infective effects in human infants.', \"To study effects of consumption of raw and processed cow's milk on common infections in infants.\", \"The PASTURE birth cohort followed 983 infants from rural areas in Austria, Finland, France, Germany, and Switzerland, for the first year of life, covering 37,306 person-weeks. Consumption of different types of cow's milk and occurrence of rhinitis, respiratory tract infections, otitis, and fever were assessed by weekly health diaries. C-reactive protein levels were assessed using blood samples taken at 12 months.\", 'When contrasted with ultra-heat treated milk, raw milk consumption was inversely associated with occurrence of rhinitis (adjusted odds ratio from longitudinal models [95% CI]: 0.71 [0.54-0.94]), respiratory tract infections (0.77 [0.59-0.99]), otitis (0.14 [0.05-0.42]), and fever (0.69 [0.47-1.01]). Boiled farm milk showed similar but weaker associations. Industrially processed pasteurized milk was inversely associated with fever. Raw farm milk consumption was inversely associated with C-reactive protein levels at 12 months (geometric means ratio [95% CI]: 0.66 [0.45-0.98]).",
            "output": [
                "Does consumption of unprocessed cow 's milk protect infants from common respiratory infections?"
            ]
        },
        {
            "id": "task847-d1c5ad05a3ac4456a25c6201cb12499b",
            "input": "Neurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties.', 'Compound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug-prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia.', 'ITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration-dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2-antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re-oxygenation from stress by increasing the expression of haem oxygenase-1 and reducing free radical production.",
            "output": [
                "Does melatonin-sulforaphane hybrid ITH12674 induce neuroprotection in oxidative stress conditions by a 'drug-prodrug ' mechanism of action?"
            ]
        },
        {
            "id": "task847-da13c1a18da94bd4b26e6f51b9131882",
            "input": "Current basic or more advanced methods for analysis of averaged EEG/ERP are based on assumptions on the underlying processes, which are not necessarily precise.', 'In this work we present the findings of a method which obviates such assumptions and aims at a comprehensive analysis of the averaged EEG/ERP signal.', 'For the sake of demonstration we chose the established go/no-go paradigm in the context of ADHD. Our analysis method characterized two spatiotemporally distinct neurophysiologic processes which underlie the sampled signal: one which may be related to attention and the other which may be more related to perception.",
            "output": [
                "Does comprehensive analysis suggest simple processes underlying EEG/ERP - demonstration with the go/no-go paradigm in ADHD?"
            ]
        },
        {
            "id": "task847-6a8a5e2c830d435c9d3b32478ab4c33f",
            "input": "Are the fetal membranes of women affected with endometriosis similar to those from disease-free women?",
            "output": [
                "Does endometriosis also affect the decidua in contact with the fetal membranes during pregnancy?"
            ]
        },
        {
            "id": "task847-41aa9c54e3b84c4ea095122156c73665",
            "input": "Do endometriotic ovarian cysts influence the rate of spontaneous ovulation?",
            "output": [
                "Do endometriotic ovarian cysts negatively affect the rate of spontaneous ovulation?"
            ]
        },
        {
            "id": "task847-a07b7e930e74440eb7a7e7649d5736b6",
            "input": "Urbanization can considerably impact animal ecology, evolution, and behavior. Among the new conditions that animals experience in cities is anthropogenic noise, which can limit the sound space available for animals to communicate using acoustic signals. Some urban bird species increase their song frequencies so that they can be heard above low-frequency background city noise. However, the ability to make such song modifications may be constrained by several morphological factors, including bill gape, size, and shape, thereby limiting the degree to which certain species can vocally adapt to urban settings. We examined the relationship between song characteristics and bill morphology in a species (the house finch, Haemorhous mexicanus) where both vocal performance and bill size are known to differ between city and rural animals.', 'We found that bills were longer and narrower in more disturbed, urban areas. We observed an increase in minimum song frequency of urban birds, and we also found that the upper frequency limit of songs decreased in direct relation to bill morphology.",
            "output": [
                "Do song characteristics track bill morphology along a gradient of urbanization in house finches ( Haemorhous mexicanus )?"
            ]
        },
        {
            "id": "task847-af9a0cbbfd3040d8ad47180bfd9681a0",
            "input": "According to reports in the literature, more than 30% of depressive patients fail to achieve remission. Therapy with the conventional antidepressant drugs may induce the serious adverse reactions. Moreover, its benefits may be seen at least 2-4 weeks after the first dose. Therefore, the alternative strategies for prevention and treatment of depression are sought. The main aim of our study was to assess the effects of ifenprodil given at a non-active dose (10mg/kg) on the activity of antidepressant agents from diverse pharmacological groups.', 'The antidepressant-like effect was assessed by the forced swim test in mice.', 'Ifenprodil potentiated the antidepressant-like effect of imipramine (15mg/kg) and fluoxetine (5mg/kg) while did not reduce the immobility time of animals which simultaneously received reboxetine (2.5mg/kg) or tianeptine (15mg/kg).",
            "output": [
                "Do the effects of ifenprodil on the activity of antidepressant drugs in the forced swim test in mice?"
            ]
        },
        {
            "id": "task847-d36ab121806a4d38a6b2cab846b50354",
            "input": "POEMS syndrome is a plasma cell disorder manifested by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. Pulmonary morbidity includes restriction, decreased diffusing capacity for carbon monoxide (DLCO), respiratory muscle weakness, abnormal imaging, and pulmonary hypertension. Autologous peripheral blood stem cell transplantation (aPBSCT) is an effective treatment for POEMS syndrome. It is unknown if aPBSCT improves pulmonary morbidity. We hypothesize pulmonary morbidity will improve following aPBSCT.', \"Retrospective cohort study of POEMS syndrome aPBSCT recipients from 2000 to 2010. Demographic, pulmonary function test (PFT), echocardiogram, cytokine, and imaging data at baseline and after aPBSCT were abstracted. Pre- and post-transplant data were compared using Wilcoxon signed-rank and McNemar's tests.\", '53 patients met criteria. Median improvements in forced expiratory volume in 1\\xa0s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) after transplant were 180, 315 and 350\\xa0ml respectively (median follow-up of 1.1 years). DLCO, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) improved by a median of 11, 12.5 and 10% predicted respectively. RVSP and chest imaging also improved. Vascular endothelial growth factor and IL-6 decreased by a median of 334 and 2\\xa0pg/ml respectively. All comparisons were statistically significant. Longitudinal data demonstrated stability in FEV1, MEP, and TLC and continued improvement in FVC, MIP and DLCO on subsequent PFTs (median follow-up 26.5 months).",
            "output": [
                "Does pulmonary morbidity improve after autologous stem cell transplantation in POEMS syndrome?"
            ]
        },
        {
            "id": "task847-b6748b3a49414802af75b835563e2bd6",
            "input": "It is well known that cyclooxygenase-2 (COX-2) and its major derivative product prostaglandin E2 (PGE2) play key regulatory roles in the ovulation process. Animal studies have demonstrated that the inhibition of nitric oxide (NO) suppresses ovarian PGE2 production and ovulation. Although the expression of NO synthases has been detected in human granulosa cells, the effect of NO on COX-2 expression and PGE2 production in these cells remains unknown.', 'The purpose of this article was to investigate the effects of NO on COX-2 expression and PGE2 production in human granulosa cells.', 'SVOG cells are human granulosa cells that were obtained from women undergoing in vitro fertilization and immortalized with simian virus 40 large T antigen. SVOG cells were used to investigate the effects of NO on COX-2 expression and PGE2 production.', 'The study was conducted in an academic research center.', 'The levels of mRNA and protein were examined by RT-quantitative real-time PCR and Western blotting, respectively. The accumulation levels of PGE2 were measured by ELISA.', 'Treatment with the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) induced COX-2 expression and PGE2 production. In addition, the stimulatory effect of SNAP on COX-2 and PGE2 was mimicked by treatment with the cGMP analog 8-bromo-cGMP (8-Br-cGMP). Interestingly, neither SNAP nor 8-Br-cGMP affected the expression of COX-1. Moreover, our results showed that either SNAP or 8-Br-cGMP activated cAMP response element-binding protein (CREB) signaling and that the knockdown of CREB attenuated SNAP- and 8-Br-cGMP-induced COX-2 expression and PGE2 production.",
            "output": [
                "Do nitric oxide and cGMP induce COX-2 expression and PGE2 production in human granulosa cells through CREB signaling pathway?"
            ]
        },
        {
            "id": "task847-54fe167e33d94de6947d4f7327c37b0a",
            "input": "Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. It has been demonstrated that micro-RNAs (miRNAs) are involved in the development of PTC. The miRNA-chromatin immunoprecipitation microarray assay revealed down-regulation of miR-219-5p; however, the effect of miR-219-5p on PTC cell growth remains unknown. This result implied the critical role of miR-219-5p in the development of PTC.', 'We investigated the association between miR-219-5p and PTC development. Expression of miR-219-5p was monitored in 30 PTC tissue specimens and compared with that in 30 normal thyroid tissue specimens. The effect of miR-219-5p on PTC development was studied by cell proliferation, migration, and apoptosis assays. The underlying mechanism was clarified by a reporter assay and rescue experiment.', 'The current study confirmed that miR-219-5p expression was inhibited in PTC tissue samples. There were statistically significant differences in the expression of miR-219-5p with regard to sex, tumor size, and lymph node metastasis in patients with PTC. Forced expression of miR-219-5p suppressed PTC cell proliferation and migration and promoted apoptosis. Further study showed that estrogen receptor (ER) \u03b1 was the direct target of miR-219-5p and mediated the effect of miR-219-5p on PTC occurrence. Expression of miR-219-5p was inversely correlated with that of ER\u03b1. Importantly, ER\u03b1 overexpression in PTC cells rescued the inhibitory effect of miR-219-5p on PTC cell proliferation and migration. Thus, our results indicated that miR-219-5p played a critical role in PTC growth by inhibiting ER\u03b1.",
            "output": [
                "Does miR-219-5p modulate cell growth of papillary thyroid carcinoma by targeting estrogen receptor \u03b1?"
            ]
        },
        {
            "id": "task847-1aa712b5c06c49f5891a705ea2e28994",
            "input": "Growing evidence implicates hypothalamic inflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Few studies have addressed the association between obesity and hypothalamic damage in humans and its relevance.', 'This study aimed to determine markers of obesity-associated hypothalamic damage on diffusion tensor imaging (DTI) and to determine whether DTI metrics are associated with performance on cognitive testing.', 'This cross-sectional study analyzed DTI metrics (primary [\u03bb(1)], secondary [\u03bb(2)], and tertiary [\u03bb(3)] eigenvalues; fractional anisotropy; and mean diffusivity) in the hypothalamus of 24 consecutive middle-age obese subjects (13 women; 49.8 \u00b1 8.1 y; body mass index [BMI], 43.9 \u00b1 0.92 kg/m(2)) and 20 healthy volunteers (10 women; 48.8 \u00b1 9.5 y; BMI, 24.3 \u00b1 0.79 kg/m(2)).', 'measures: Hypothalamic damage assessed by DTI metrics and cognitive performance evaluated by neuropsychological test battery.', '\u03bb(1) values in the hypothalamus were significantly lower in obese subjects (P < .0001). The sensitivity, specificity, and positive and negative predictive values for obesity-associated hypothalamic damage by \u03bb(1) < 1.072 were 75, 87.5, 83.3, and 80.7%, respectively. Patients with hypothalamic \u03bb(1) < 1.072 had higher values of BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests. Combined BMI and alanine aminotransferase had the strongest association with hypothalamic damage reflected by \u03bb(1) < 1.072 (area under the curve = 0.89).",
            "output": [
                "Is hypothalamic damage associated with inflammatory markers and worse cognitive performance in obese subjects?"
            ]
        },
        {
            "id": "task847-9359600efc334658a21ed92e54995b8a",
            "input": "Anaplastic thyroid carcinoma (ATC) is one of the most deadly human malignancies. It is 99% lethal, and patients have a median survival of only 6 months after diagnosis. Despite these grim statistics, the mechanism underlying the tumorigenic capability of ATC cells is unclear.', 'S100A8 and S100A9 proteins have emerged as critical mediators in cancer. The aim was to investigate the expression and function of S100A8 and S100A9 in ATC and the mechanisms involved.', 'We determined the expression of S100A8 and S100A9 in human ATC by gene array analysis and immunohistochemistry. Using RNAi-mediated stable gene knockdown in human ATC cell lines and bioluminescent imaging of orthotopic and lung metastasis mouse models of human ATC, we investigated the effects of S100A8 and S100A9 on tumorigenesis and metastasis.', 'We demonstrated that S100A8 and S100A9 were overexpressed in ATC but not in other types of thyroid carcinomas. In vivo analysis in mice using ATC cells that had S100A8 knocked down revealed reduced tumor growth and lung metastasis, as well as significantly prolonged animal survival. Mechanistic investigations showed that S100A8 promotes ATC cell proliferation through an interaction with RAGE, which activates the p38, ERK1/2 and JNK signaling pathways in the tumor cells.",
            "output": [
                "Is s100A8 a novel therapeutic target for anaplastic thyroid carcinoma?"
            ]
        },
        {
            "id": "task847-9043c21abb814f8d834dda7c3d247950",
            "input": "Faster resting heart rate (HR), which is associated with inflammation and elevated cortisol levels, is a risk factor for excess cardiovascular morbidity and mortality. Obesity is associated with increased cardiovascular morbidity and mortality, inflammation, and elevated cortisol levels. The aim of the present study was to evaluate the interaction of Body Mass Index (BMI) with inflammation and cortisol in modulating HR in older subjects.', 'We analyzed data of 895 participants aged 65+ enrolled in the \"InCHIANTI\" study, in sinus rhythm, and not taking beta blockers or digoxin. Linear regression was performed to assess the adjusted association between HR, IL-6, and cortisol levels. The model was also analyzed stratifying for BMI tertiles. Logistic regression was adopted for evaluating the association of HR exceeding the mean value with Il-6 and serum cortisol.', 'According to multivariable linear regression, IL-6 and cortisol levels were associated with HR (B = 1.42, 95% CI = 0.43-2.42; p = .005 and B = .34, 95% CI = 0.17-.51; p < .0001, respectively). The association was significant only among women in the highest BMI tertile (B = 4.16, 95% CI = 1.40-6.91; p = .003 for IL-6 and B = .57, 95% CI = 0.14-1.01; p = .010 for cortisol). Logistic regression confirmed that IL-6 and cortisol levels were associated with HR above the mean value in the highest BMI tertile (OR = 2.13, 95% CI = 1.15-3.97; p = .009 and OR = 1.14, 95% CI = 1.03-1.25; p = .009, respectively).",
            "output": [
                "Do associations of Heart Rate With Inflammatory Markers Are Modulated by Gender and Obesity in Older Adults?"
            ]
        },
        {
            "id": "task847-c158f1d85b8a4d53bfccf2828cc226a3",
            "input": "Clonal plants can plastically modify their traits in response to competition, but little is known regarding the spatio-temporal scale at which a competitive neighbourhood determines the variability in species traits. This study tests the hypothesis that the local neighbourhood can be expected to influence the processes that are involved in competition tolerance and avoidance, and that this effect depends on organ lifespan.', 'Fragments of the rhizomatous Elytrigia repens (Poaceae) were sampled in 2012 in experimental plant communities that varied in species identity and abundance. These communities had been cultivated since 2009 in mesocosms in a common garden. Fragment performance, shoot and clonal traits were measured, and the effects of past and present local neighbourhoods of five different radius sizes (5-25\\u2009cm) were examined. Past and present local neighbourhood compositions were assessed in 2011 and 2012, respectively.', 'Most of the measured traits of E. repens responded to the local neighbourhood (5-10\\u2009cm radius), with an additional effect of the larger neighbourhood (20-25\\u2009cm radius) on ramet height, leaf dry matter content, maximal internode length and specific rhizome mass. Contrary to the expectation of the hypothesis, the temporal influence was not due to the organ lifespan. Indeed, five of the eight traits studied responded to both the past and present neighbourhoods. With the exception of specific rhizome mass, all trait responses were explained by the abundance of specific species.",
            "output": [
                "Do plant traits respond to the competitive neighbourhood at different spatial and temporal scales?"
            ]
        },
        {
            "id": "task847-d73db28c1e664d0c8d3f0ec2e2da9142",
            "input": "Patients with familial adenomatous polyposis (FAP) are prone to developing duodenal adenoma and cancer. Optimal surveillance and management of these adenomas are not well established.', 'We assessed the outcome of FAP patients undergoing intense multimodal surveillance and subsequent endoscopic resection of advanced lesions.', 'Eighty consecutive FAP patients enrolled during 2001 to 2011 from the Familial Cancer Clinic of a tertiary hospital as part of routine surveillance.', 'Case series, prospective in years 2006 to 2011 and retrospective in years 2001 to\\xa02006.', 'Patients were followed by annual forward-view and/or side-view upper endoscopy. A\\xa0biopsy sample was obtained from visible lesions and normal papillae. Ampullary adenomas were further assessed by EUS to determine dimensions and resectability. Advanced adenomas (size\\xa0\u2265 10\\xa0mm, villous type, high-grade dysplasia) underwent endoscopic ampullectomy or polypectomy and continued surveillance.', 'Detection of advanced adenomas by endoscopy and EUS, endoscopic maintenance of duodenum free of advanced adenoma and cancer.', 'Patients (38 men and 42 women, mean age 32.68 \u00b1 13.60) were followed 7.2 years and underwent 5.36\\xa0diagnostic studies on average. Thirty-eight patients had ampullary adenomas. Advanced adenoma was diagnosed by endoscopy in 10 patients. Importantly, EUS upstaged 9 additional patients to advanced adenoma and downstaged 1, thus altering the treatment course in 36% of patients performing EUS. Endoscopic ampullectomy was performed in 15 patients. Adenoma recurred in 10. Five remained nonadvanced and 5 in advanced stages: 3 were successfully retreated endoscopically and 2 ultimately required surgery for residual adenoma. Advanced nonampullary adenomas were successfully resected endoscopically in 23 patients. No patient had duodenal cancer during the study period.",
            "output": [
                "Are endoscopy and EUS key for effective surveillance and management of duodenal adenomas in familial adenomatous polyposis?"
            ]
        },
        {
            "id": "task847-51737e472de8476b86fa4dff9aba61f1",
            "input": "We aimed to select true groove pancreatic ductal adenocarcinomas (GPDACs) and define their specific features.', 'We performed histopathologic and immunohistochemical comparisons of 6 GPDACs with 6 duodenal adenocarcinomas (DACs) and 24 conventional pancreatic ductal adenocarcinomas (cPDACs). Both groups were adjusted to ensure similar mean tumor size.', 'Representative loupe image showed prominent duodenal invasion and slight pancreatic invasion. Groove pancreatic ductal adenocarcinomas exhibited different mucins and cytokeratin profiles in DACs, but cPDACs and small branch pancreatic ducts had the same profiles. Histopathologic analysis of GPDACs showed a significantly higher incidence of duodenal invasion and well differentiation than cPDACs, although the incidences of lymph node metastasis, angiolymphatic invasion, and neural invasion were similar. Immunohistochemical analysis of GPDACs showed a significantly lower frequency of abnormal Smad4 immunolabeling, and fewer GPDAC samples exhibited abnormal immunolabeling for MUC1, p16, Smad4, and p53 than cPDACs.",
            "output": [
                "Are well differentiation and intact Smad4 expression specific features of groove pancreatic ductal adenocarcinomas?"
            ]
        },
        {
            "id": "task847-0338a93b12494700ab602c80f67e2cdb",
            "input": "The aim of this study was to investigate the role of peroxiredoxin 1 (Prdx1) in the invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells.', 'Immunohistochemistry was used to determine overexpression of Prdx1 in human PDAC tissues. Immunoprecipitation and immunocytochemistry were used to determine the interaction and intracellular distribution of Prdx1 and a member of the mitogen-activated protein kinase (MAPK) family protein, p38 MAPK, in PDAC cells. Finally, immunocytochemistry and Matrigel invasion assay were used to examine the effects of Prdx1 and p38 MAPK on the formation of cell protrusions and PDAC cell invasion.', 'Prdx1 is overexpressed in human PDAC tissues. Peroxiredoxin 1 interacts with active forms of p38 MAPK, and complexes of Prdx1 and phosphorylated p38 MAPK localize at the leading edges of migrating PDAC cells. Suppression of Prdx1 decreases active p38 MAPK localized in cell protrusions and inhibits the invasiveness of PDAC cells. Consequently, suppression of Prdx1 inhibits membrane ruffling and protrusions. The p38 MAPK inhibitor SB203580 also decreases the formation of membrane protrusions and inhibits invasiveness.",
            "output": [
                "Does peroxiredoxin 1 promote pancreatic cancer cell invasion by modulating p38 MAPK activity?"
            ]
        },
        {
            "id": "task847-46cf04ff9d6f4e81967e4510fcc5fd3f",
            "input": "The interleukin (IL)-23/IL-17 axis plays an important role in various inflammatory conditions but its function in acute pancreatitis (AP) is not well understood. The present study investigated the relationship between serum levels of IL-23, IL-17, and C-reactive protein (CRP) in patients and the severity of AP.', 'Eighty-five patients with AP were categorized into mild group, moderately severe group, and severe group according to the revised Atlanta classification, 2012. Serum levels of IL-23 and IL-17 were measured by enzyme-linked immunosorbent assay in patients 48 hours after admission. The CRP levels of patients were also measured on admission and 48 hours after admission.', 'The serum levels of CRP of patients on admission and 48 hours after admission and levels of IL-23 and IL-17 of patients 48 hours after admission increased alone with the severity of AP, respectively (P < 0.01). The serum levels of IL-23 and IL-17 in the patients were correlated with CRP levels (r = 0.234, r = 0.552, P < 0.001, respectively).",
            "output": [
                "Do increased interleukin-23/17 axis and C-reactive protein are associated with severity of acute pancreatitis in patients?"
            ]
        },
        {
            "id": "task847-67fac4e1d1c248ccb75dc27099e35c11",
            "input": "Waist-to-height ratio (WHtR) is a cardiometabolic risk indicator in children. A value greater than or equal to 0.55 is an effective screening tool for identifying obese children with metabolic syndrome. However, it is unclear whether this cutoff can be applied equally to any age or gender.', 'To analyze the variability of WHtR by age, gender and pubertal stage in elementary school children.', 'Cross-sectional study in 2,980 school children (6-14 years old, 51% male) of Santiago, Chile. We measured weight, height and waist circumference and calculated body mass index and WHtR. Pubertal stage was assessed and classified as peripubertal (Tanner I and II) and pubertal (Tanner III, IV and V).', 'The mean age was 9.9 \u00b1 2.3 years, with no gender difference (p = 0.5). Eighty one percent of boys and 59.4% of girls were peripubertal (p < 0.001). The association between age-adjusted WHtR by gender and pubertal stage was not significant (p = 0.409). Therefore mean, standard deviation and percentiles of WHtR were calculated without sex and pubertal stage segmentations.",
            "output": [
                "Does [ Waist-to-height ratio change with gender , age and pubertal stage in elementary school children ]?"
            ]
        },
        {
            "id": "task847-9e69e6428cbe48d6bee2b4e81bace623",
            "input": "To investigate whether premorbid maternal and childhood psychological problems are risk factors for chronic disabling fatigue at age 13 years among children in the Avon Longitudinal Study of Parents and Children birth cohort.', 'Chronic disabling fatigue was defined as fatigue of at least 3-month, and up to 5-year, duration that prevented school attendance or hobbies/sport/leisure activities, and for which other causes were not identified. Maternal psychological factors were symptoms of anxiety and depression assessed up to eight times between pregnancy and age 6 years. We investigated critical periods for maternal effects and effects of paternal depression at three time points. Child psychological factors included internalizing and externalizing problems and upsetting life events occurring at age 7-8 years.', 'Of 5,657 children, 110 (1.9%) had chronic disabling fatigue at age 13 years. Maternal anxiety (adjusted odds ratio [AOR], 1.19; 95% confidence interval [CI], 1.09-1.31 per episode), maternal depression (AOR, 1.24; CI, 1.11-1.39 per episode), child psychological problems (AOR, 1.19; CI, 1.00-1.41 per problem), and upsetting events (AOR, 1.22; CI, .99-1.58 per event) were associated with chronic disabling fatigue. Associations of child psychological problems and upsetting events were attenuated (AOR, 1.12; CI, .93-1.33 per problem; AOR, 1.19; CI, .94-1.52 per event) after further adjusting for maternal anxiety and depression.",
            "output": [
                "Do maternal and childhood psychological factors predict chronic disabling fatigue at age 13 years?"
            ]
        },
        {
            "id": "task847-e6172f1dce1241ec99831f351c7771e6",
            "input": "To assess the rate and risk factors for position-related injury in robotic gynecologic surgery.', 'A prospective database from 12/2006 to 1/2014 of all planned robotic gynecologic procedures was retrospectively reviewed for patients who experienced neurologic injury, musculoskeletal injury, or vascular compromise related to patient positioning in the operating room. Analysis was performed to determine risk-factors and incidence for position-related injury.', 'Of the 831 patients who underwent robotic surgery during the study time period, only 7 (0.8%) experienced positioning-related injury. The injuries included minor head contusions (n=3), two lower extremity neuropathies (n=2), brachial plexus injury (n=1) and one large subcutaneous ecchymosis on the left flank and thigh (n=1). There were no long term sequelae from the positioning-related injuries. The only statistically significant risk factor for positioning-related injury was prior abdominal surgery (P=0.05). There were no significant associations between position-related injuries and operative time (P=0.232), body mass index (P=0.847), age (P=0.152), smoking history (P=0.161), or medical comorbidities (P=0.229-0.999).",
            "output": [
                "Is position-related injury uncommon in robotic gynecologic surgery?"
            ]
        },
        {
            "id": "task847-aa44f08bf3b640c08d012ad37a800825",
            "input": "Stress neurocircuitry may modulate the relationship between alcohol drinking and chronic pain. The corticotropin-releasing factor (CRF) system is crucial for regulation of stress responses. The current study aimed to elucidate the role of the endogenous CRF ligand Urocortin 3 (Ucn3) in the relationship between alcohol drinking behavior and chronic pain using a genetic approach.', 'Ucn3 (KO) and wildtype (WT) littermates were subjected to a 24-h access drinking procedure prior to and following induction of chronic inflammatory pain.', 'Ucn3 KO mice displayed significantly increased ethanol intake and preference compared with WT across the time course. There were no long-term effects of chronic pain on alcohol drinking behavior, regardless of genotype, nor any evidence for alcohol-induced analgesia.",
            "output": [
                "Is increased alcohol consumption in urocortin 3 knockout mice unaffected by chronic inflammatory pain?"
            ]
        },
        {
            "id": "task847-3afa251d3e97444eae9cfa5db22286f7",
            "input": "The aim of this study was to investigate the prognostic effect of serum free light chain (sFLC) response after 2 cycles of first-line chemotherapy (CT) in multiple myeloma (MM) patients.', 'The data of 78 newly diagnosed MM patients who had sFLC levels at diagnosis and after 2 cycles of first-line CT were included in the study. The prognostic effect of sFLCs were evaluated with normalization of sFLC \u03ba/\u03bb ratio after 2 cycles of CT and involved/uninvolved (i/u) sFLCs.', 'At the end of follow-up the probability of overall survival (OS) was 95.7% versus 68.5% in patients with and without normalized sFLC \u03ba/\u03bb ratio, respectively (P = .072). The probability of OS with i/u sFLC assessment was 97.4% versus 55.8% with regard to i/u sFLC \u2264 10 and > 10, respectively (P = .001). In univariate and multivariate analysis including sFLC ratio, age, sex, and International Staging System, i/u sFLC ratio > 10 after 2 cycles of CT was identified as an independent risk factor for OS (P = .015; hazard ratio [HR], 13.2; 95% confidence interval [CI], 1.668-104.65 vs. P = .011; HR, 15.17; 95% CI, 1.85-123.89).",
            "output": [
                "Does serum free light chain response after 2 courses of induction chemotherapy predict prognosis in myeloma patients?"
            ]
        },
        {
            "id": "task847-1115d0df4b054d53a0d3416ebab5add6",
            "input": "A Chinese herb Corydalis yanhusuo W.T. Wang that showed anticancer and anti-angiogenesis effects in our previous studies was presented for further studies. In the present study, we studied the anticancer proliferation and adhesion effects of five alkaloids which were isolated from Corydalis yanhusuo.', 'MTT dose response curves, cell migration assay, cell invasion assay, as well as three types of cell adhesive assay were performed on MDA-MB-231 human breast cancer cells. The mechanism of the compounds on inhibiting heterotypic cell adhesion were further explored by determining the expression of epidermal growth factor receptor (EGFR), Intercellular adhesion molecule 1 (ICAM-1), \u03b1v-integrin, \u03b21-integrin and \u03b25-integrin by western blotting assay.', 'In five tested alkaloids, only protopine exhibited anti-adhesive and anti-invasion effects in MDA-MB-231 cells, which contributed to the anti-metastasis effect of Corydalis yanhusuo. The results showed that after treatment with protopine for 90 min, the expression of EGFR, ICAM-1, \u03b1v-integrin, \u03b21-integrin and \u03b25-integrin were remarkably reduced.",
            "output": [
                "Does protopine inhibit heterotypic cell adhesion in MDA-MB-231 cells through down-regulation of multi-adhesive factors?"
            ]
        },
        {
            "id": "task847-505b33e18cd84baa8eaa5c804292cef1",
            "input": "The present study was designed to investigate whether H2S can protect testicular germ cells against heat exposure induced injury and the underlying mechanisms.', 'It was found that all three H2S generating enzymes, cystathionine \u03b2-synthase (CBS), cystathionine \u03b3-lysase (CSE), and 3-mercaptopyruvate sulfurtransferase (3 MST), were expressed in mouse testicular tissue. Three episodes of heat exposure (42 \u00b0C, 30 min/day, 3 days) significantly decreased endogenous H2S production and down-regulated the expression of CBS and CSE in testes. In primary cultured testicular germ cells, exogenous application of NaHS (an H2S donor) attenuated heat stress (42 \u00b0C, 30 min) induced cell death and apoptosis. This was mediated by the inhibitory effects of H2S on cytochrome C release and the ratio of the Bax/Bcl-2. NaHS also improved mitochondrial function by decreasing oxygen consumption and increasing ATP production. NaHS treatment also stimulated SOD activity and reduced ROS production.",
            "output": [
                "Does hydrogen sulfide protect testicular germ cells against heat-induced injury?"
            ]
        },
        {
            "id": "task847-ca33b7b8ff284379aa50a85137af61c7",
            "input": "Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa.', '120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression.', '5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues.",
            "output": [
                "Is long noncoding RNA PCA3 gene promoter region related to the risk of prostate cancer on Chinese males?"
            ]
        },
        {
            "id": "task847-3696a11b50944417b514564e30bf651e",
            "input": "The aim of the present work was to investigate the mechanism of transforming growth factor (TGF)-\u03b21 and Sloan-Kettering Institute (Ski) in the pathogenesis of hypertrophic scars (HS).', 'Wound healing is an inherent process, but the aberrant wound healing of skin injury may lead to HS. There has been growing evidence suggesting a role for TGF-\u03b21 and Ski in the pathogenesis of fibrosis.', 'The MTT assay was used to detect the cell proliferation induced by TGF-\u03b21. The Ski gene was transduced into cells with an adenovirus, and then the function of Ski in cell proliferation and differentiation was observed. Ski mRNA levels were measured by RT-PCR. Western blotting was used to detect the protein expression of \u03b1-SMA, E-cadherin, Meox1, Meox2, Zeb1 and Zeb2.', 'TGF-\u03b21 can promote human skin fibroblast (HSF) cell proliferation in a time-dependent manner, but the promoting effect could be suppressed by Ski. TGF-\u03b21 also induces the formation of the myofibroblast phenotype and the effect of TGF-\u03b21 could be diminished by Ski. Also, Ski modulates the cardiac myofibroblast phenotype and function through suppression of Zeb2 by up-regulating the expression of Meox2.",
            "output": [
                "Does ski diminish TGF-\u03b21-induced myofibroblast phenotype via up-regulating Meox2 expression?"
            ]
        },
        {
            "id": "task847-70dd967746c14c9b894c2f4c5328ff82",
            "input": "Impaired resolution of acute inflammation results in development of chronic inflammatory disorders such as atherosclerosis, asthma and arthritis. Clearance of apoptotic neutrophils by M2 macrophages, the process termed efferocytosis, is critical for complete resolution of inflammation as it prevents secondary necrosis caused by disgorgement of toxic contents from apoptotic cells in the inflamed site. In the present study, we investigated the effect of docosahexaenoic acid (DHA) on efferocytosis.', 'To determine the effect of DHA on efferocytosis, murine macrophage-like RAW264.7 cells were co-incubated with apoptotic Jurkat T cells, and efferocytosis was assessed by flow cytometry. The expression and production of M1 and M2 markers were determined by RT-PCR, ELISA and flow cytometry. To demonstrate the involvement of peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) in DHA-mediated effects, siRNA against PPAR\u03b3 was utilized. The expression of PPAR\u03b3 was examined by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), Western blot analysis and immunocytochemistry. The PPAR\u03b3 activation was measured by the electrophilic gel shift assay.', 'DHA enhanced the efferocytic ability of RAW264.7 cells, and induced their M2 polarization. Notably, knockdown of PPAR\u03b3 abolished the stimulatory effect of DHA on M2 polarization as well as efferocytosis. Furthermore, lipopolysaccharide-induced production of pro-inflammatory cytokines was significantly inhibited by DHA, suggesting that DHA alters the macrophage phenotype in favor of M2 while it suppresses M1 polarization.",
            "output": [
                "Does docosahexaenoic acid induce M2 macrophage polarization through peroxisome proliferator-activated receptor \u03b3 activation?"
            ]
        },
        {
            "id": "task847-2df61c8dcec244a9a43461a9b56c8fd8",
            "input": "Immunohistochemistry (IHC) is a well-established, widely accepted method in both clinical and experimental parts of medical science. It allows receiving valuable information about any process in any tissue, and especially in bone. Each year the amount of data, received by IHC, grows in geometric progression. But the lack of standardization, especially on the post-analytical stage (interpreting and reporting of results), makes the comparison of the results of different studies impossible.', 'Comprehensive PubMED literature search with a combination of search words \"immunohistochemistry\" and \"scoring system\" was performed and 773 articles describing IHC results were identified. After further manual analysis 120 articles were selected for detailed evaluation of used approaches.', 'Six major approaches to the interpretation and presentation of IHC analysis results were identified, analyzed and described.",
            "output": [
                "Does different approaches for interpretation and reporting of immunohistochemistry analysis result in the bone tissue - a review?"
            ]
        },
        {
            "id": "task847-23cd6d1ec3d241228a536d4ec52aca69",
            "input": "The aim of this study was to investigate the attitudes and perceptions of staff radiologists regarding the incorporation of a nonanonymous peer review system at an academic hospital.', 'A questionnaire gauging knowledge of, attitudes toward, and perceptions regarding peer review was distributed to all staff radiologists at a large academic hospital. The survey was distributed before the implementation of a nonanonymous peer review system. Data were analyzed using descriptive statistics. Responses were cross-tabulated according to subspecialty and number of years in practice.', 'The majority of respondents agreed that peer review is important for improving patient care (31 of 36 [86%]) and professional development (29 of 36 [81%]), but the vast majority (33 of 36 [92%]) believed that peer review should be anonymous. Twenty-six of 36 respondents (72%) believed that peer review will not be safe from malpractice issues, 24 of 36 (67%) agreed that it has the potential to damage interpersonal relationships within the department, and 15 of 36 (42%) believed that it may influence their job security or rankings within the department. Significant differences were identified between radiologists with more and fewer years of practice experience.",
            "output": [
                "Do survey of radiologist attitudes and perceptions regarding the incorporation of a departmental peer review system?"
            ]
        },
        {
            "id": "task847-1d47e3fdd0c348ada539c2646bb2b29f",
            "input": "Mitochondrial dysfunction has been well documented in age related disorders like Alzheimer's disease. Alterations in mitochondrial membrane potential lead to neuronal death by excessive generation of free radicals, inflammatory cytokines, and excitotoxins. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental model of Alzheimer's disease. Naringin is a potent antioxidant, which can cross the blood brain barrier protecting brain tissue and modulating brain chemistry.\", 'The present study was designed to evaluate the effect of naringin, in ICV STZ-induced mitochondrial dysfunction and memory loss in rats.', 'Streptozotocin (3mg/kg, ICV) was injected bilaterally in two divided doses on first and third day followed by treatment with different doses of naringin (50, 100 and 200mg/kg; p.o.) for twenty one days. Behavioral alterations were monitored using Morris water maze paradigm and elevated plus maze test. Animals were sacrificed to evaluate various biochemical and mitochondrial parameters in brain. Rivastigmine was used as a standard drug.', 'ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced oxidative-nitrosative stress, altered acetylcholinesterase and mitochondrial enzyme activities in cerebral cortex and hippocampus of rats brain along with significantly increased brain TNF-\u03b1 and IL-1\u03b2 levels. Chronic treatment with naringin dose dependently restored cognitive deficits in ICV-STZ rat along with mitigation of mitochondrial dysfunction mediated oxido-nitrosative stress and cytokine release.",
            "output": [
                "Does naringin ameliorate memory deficits in experimental paradigm of Alzheimer 's disease by attenuating mitochondrial dysfunction?"
            ]
        },
        {
            "id": "task847-01c6917476654ca9b594b3652d63efe3",
            "input": "Neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia, is a devastating neurological disease that seriously affects patients' quality of life. We have previously shown that tanshinone IIA (TIIA), an important lipophilic component of Danshen, had significant anti-nociceptive effect in somatic and visceral pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA on neuropathic pain and the underlying mechanisms. Therefore, in the present study, by using spinal nerve ligation (SNL) pain model, the antinociceptive and antihyperalgesic effects of TIIA on neuropathic pain were evaluated by intraperitoneal administration in rats. The results indicated that TIIA dose-dependently inhibited SNL-induced mechanical hyperalgesia. As revealed by OX42 levels, TIIA effectively repressed the activation of spinal microglial activation in SNL-induced neuropathic pain. Meanwhile, TIIA also decreased the expressions of inflammatory cytokines TNF-\u03b1 and IL-1\u03b2 in the spinal cord. Furthermore, TIIA inhibited oxidative stress by significantly rescuing the superoxide dismutase (SOD) activity and decreasing the malondialdehyde (MDA). Moreover, TIIA depressed SNL-induced MAPKs activation in spinal cord.",
            "output": [
                "Does tanshinone IIA attenuate neuropathic pain via inhibiting glial activation and immune response?"
            ]
        },
        {
            "id": "task847-229c15af703b4fc7b28a033b12b9980d",
            "input": "In previous reports both microcirculatory alterations and impaired vascular reactivity have been described in post cardiac arrest patients treated with mild therapeutic hypothermia. As of now it is unknown whether these alterations are related to the temperature management or to the cardiac arrest itself. Aim of the present study was to investigate the potential difference in microcirculatory alterations and vascular reactivity in comatose patients after out of hospital cardiac arrest treated with target temperature management of 33 \u00b0C (TTM33) in comparison to patients treated with 36 \u00b0C (TTM36).', \"Our study was designed as a predefined substudy of the open label randomized controlled TTM trial in 2 Dutch mixed ICU's. Sublingual microvascular flow index (MFI) was assessed by Side Stream Darkfield imaging and vascular reactivity at the thenar region of the hand by near infrared spectroscopy. Variables, including systemic hemodynamics were recorded at start study (T1), after 12h (T2) and after 24h (T3).\", '22 patients were included, 13 in TTM33 and 9 in TTM36. At T1 MFI between groups did not differ significantly (1.08 [0.4-1.9] versus 1.67 [0.7-2.4] respectively, p = 0.59). The difference between groups remained insignificant over time. At T1 tissue oxygenation (StO2) was significantly lower in TTM36 in comparison to TTM33: (44.6 \u00b1 15.8 versus 58.9 \u00b1 13.5, p = 0.03). Over time this difference between groups disappeared. However, vascular reactivity, expressed as the descending and ascending slope of StO2 after a standardized ischemic occlusion test was similar between groups.",
            "output": [
                "Are microcirculatory perfusion and vascular reactivity altered in post cardiac arrest patients , irrespective of target temperature management to 33 \u00b0C vs 36 \u00b0C?"
            ]
        },
        {
            "id": "task847-fe989ee539b442eabb49d5788a54dfb6",
            "input": "Developmental dyslexia (DD) is a complex heritable condition associated with impairments in multiple neurocognitive domains. Substantial heritability has been reported for DD and related phenotypes, and candidate genes have been identified. Recently, a candidate gene for human cognitive processes, that is, GRIN2B, has been found to be associated significantly with working memory in a German DD sample. In this study, we explored the contribution of six GRIN2B markers to DD and key DD-related phenotypes by association analyses in a sample of Italian nuclear families. Moreover, we assessed potential gene-by-environment interactions on DD-related phenotypes.', 'We carried out a family-based association study to determine whether the GRIN2B gene influences both DD as a categorical trait and its related cognitive traits in a large cohort of 466 Italian nuclear families ascertained through a proband affected by DD. Moreover, we tested the role of the selected GRIN2B markers and a set of commonly described environmental moderators using a test for G\u00d7E interaction in sib pair-based association analysis of quantitative traits in 178 Italian nuclear families.', 'Evidence for a significant association was found with the categorical diagnosis of DD, performance intelligence quotient, phonemic elision, and auditory short-term memory. No significant gene-by-environment effects were found.",
            "output": [
                "Does gRIN2B mediate susceptibility to intelligence quotient and cognitive impairments in developmental dyslexia?"
            ]
        },
        {
            "id": "task847-cae35b8c20154f6d9dd0e9c3a47afe6f",
            "input": "Total bilirubin (TB) was recently recognized as an endogenous anti-inflammatory and anti-oxidant molecule. Uric acid (UA) takes part in cardiovascular diseases by inducing oxidative stress, inflammation, and endothelial dysfunction. We assessed the relationship between serum TB levels, serum UA levels, and inflammatory status assessed by neutrophil-to-lymphocyte ratio (N/L) and arterial stiffness and arterial wave reflection in patients with a clinical diagnosis of coronary artery disease (CAD).', 'We included 145 consecutive patients admitted with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood samples were drawn at admission for complete blood count and biochemistry. Non-invasive pulse waveform analysis for the determination of augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV) measurements were performed with the commercially available SphygmoCor system.', 'When patients were divided into tertiles of PWV and AIx, median N/L and median serum UA levels were the highest and mean TB levels were the lowest in the third tertile (p<0.001 for all). AIx and PWV were positively associated with serum UA and N/L and negatively associated with serum TB levels (p<0.001 for all). After adjustments for age, gender, heart rate, systolic blood pressure, and presence of diabetes, significant correlations persisted for N/L, UA, and TB in ACS patients (p<0.05). In the SAP group, TB was significantly negatively correlated with AIx and PWV, and UA was significantly positively correlated with PWV (p<0.05).",
            "output": [
                "Are arterial stiffness and central arterial wave reflection associated with serum uric acid , total bilirubin , and neutrophil-to-lymphocyte ratio in patients with coronary artery disease?"
            ]
        },
        {
            "id": "task847-09496c45b5f84728b0481f8d3443048c",
            "input": "Minimally invasive coronary artery bypass grafting (MICS CABG) via left minithoracotomy is an alternative to off-pump coronary artery bypass (OPCAB) via sternotomy. Our objective was to evaluate the clinical outcomes after MICS CABG versus OPCAB.', 'The medical records of patients who underwent MICS CABG from December 2009 to December 2011 and OPCAB from January 2005 to April 2011 were reviewed. Patients who underwent OPCAB were matched 2:1 to patients who underwent MICS CABG by age, sex, preoperative ejection fraction, creatinine concentration, as well as history of diabetes and myocardial infarction.', 'A total of 130 MICS CABG patients were matched with 260 OPCAB patients. Mean bypasses in the MICS CABG and OPCAB groups were 2.1 and 3.2, respectively (P = 0.001). Extubation in the operating room (OR) occurred in 70.0% and 12.7% of patients in the MICS CABG and OPCAB groups, respectively (P = 0.001). Mean postoperative length of stay was 4 days for the MICS CABG patients versus 5 days for the OPCAB patients (P = 0.002) and 3.8 days versus 4.6 days for the MICS CABG patients extubated in the OR compared with those who remained intubated (P = 0.007). There were no 30-day mortalities in the MICS CABG group and 1 in the OPCAB group (P = 0.999). Thirty-day readmissions were similar, with 5.4% and 7.4% in the MICS CABG and OPCAB groups, respectively (P = 0.527).",
            "output": [
                "Is minimally invasive coronary artery bypass grafting associated with improved clinical outcomes?"
            ]
        },
        {
            "id": "task847-32e4acfe138840beb3fbd7cdca47cff2",
            "input": "Some imidazoline compounds have pleiotropic effects including cell death in vitro. We examined the antiproliferative action of a novel imidazoline compound S43126, and the role of the I1-imidazoline receptor, ROS, MAPKs and caspases in S43126-induced cell death.', 'PC 12 cells were treated with various concentrations of S43126 in the presence or absence of several ligands, and the effects on cell proliferation, ROS levels, and apoptosis were evaluated using Trypan Blue, Alamar Blue, Western blot and microscopy.', 'We showed that S43126 reduced PC12 cell proliferation by greater than 50%, increased cell death by greater than 40% and increased apoptotic body formation. These effects were reversed by I1R-antagonist, efaroxan. S43126 also increased intracellular ROS levels by greater than 2.5-fold relative to vehicle-treated control. These effects were significantly inhibited by N-acetyl-cysteine. In addition, pharmacologic inhibitors of ERK, JNK and p38 MAPK, significantly reduced S43126-induced antiproliferative activity. Caspases 3, 8 and 9 were all activated in a time-dependent manner by S43126. Pan caspase inhibitor z-VAD-fmk, ameliorated the effects of S43126 on cell death and cell proliferation.",
            "output": [
                "Is antiproliferative effect induced by novel imidazoline S43126 in PC12 cells mediated by ROS , stress activated MAPKs and caspases?"
            ]
        },
        {
            "id": "task847-a8f5a0daec8d40558d3a004e8733c41a",
            "input": "Efflux transporters overexpression has been proposed as one of the responsible mechanism for refractory epilepsy by preventing access of the antiepileptic drug to the brain. In this work we investigated whether phenytoin (PHT), could induce efflux transporters overexpression, at different biological barriers and to evaluate the implication it could have on its pharmacokinetics and therapeutic/toxic response.', 'Forty-two adult females Sprague Dawley divided in five groups were treated with oral doses of 25, 50 and 75mg/kg/6h of PHT for 3 days and two additionally groups were treated with intraperitoneal (ip) doses of 25mg/kg/6h or 100mg/kg/24h. At day 4 PHT plasma concentrations were measured and, obtained several organs, brain, parotid gland, liver and duodenum in which were analyzed for the Pgp expression. At day 4 PHT plasma concentrations were measured and several tissues: brain, parotid gland, liver and duodenum were obtained in order to analyze Pgp expression. In order to evaluate the oral bioavailability of PHT, two groups were administered with oral or intraperitoneal doses of 100mg/kg and plasma level were measured.', 'An induction of the expression of efflux transporter mediated by phenytoin in a concentration-and-time dependent manner was found when increasing oral and ip doses of phenytoin, One week after the interruption of ip treatment a basal expression of transporters was recovered.",
            "output": [
                "Does chronic administration of phenytoin induce efflux transporter overexpression in rats?"
            ]
        },
        {
            "id": "task847-396204b4792b45b4a36a01457959c9c8",
            "input": "To characterize cholesterol regulation in the liver of patients with Alagille syndrome (AGS).', 'Serum total cholesterol (TC) and total bile acid (TBA) levels were measured in 23 AGS patients. The expressions of genes involved in cholesterol regulation, including low-density lipoprotein receptor (LDLR), scavenger receptor class B type I (SR-BI), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7\u03b1-hydroxylase (CYP7A1), ATP-binding cassette transporter (ABC) A1, and ABCG1/5/8, were measured in liver tissues from five of these patients. Expression of regulators for these genes, including farnesoid X receptor/small heterodimer partner (SHP), liver X receptor \u03b1 (LXR\u03b1) and mature Sterol regulatory element-binding protein 2 (SREBP2) was measured. The expression of mature SREBP2 protein was also examined.', 'Serum TC and TBA levels were correlated in the AGS patients. Liver cholesterol was also increased compared with controls, and correlated with bile acid contents. LDLR, SR-BI, HMGCR, and ABCGs mRNA expression were upregulated, while CYP7A1 mRNA expression was downregulated in AGS livers. SHP and LXR\u03b1 mRNA expression was also increased, but maturation of SREBP2 was not suppressed in the patients.",
            "output": [
                "Is negative feedback loop of cholesterol regulation impaired in the livers of patients with Alagille syndrome?"
            ]
        },
        {
            "id": "task847-c41d2fbdd7c74dccbf2beb076ce687fc",
            "input": "SULF2 is an extracellular sulfatase that acts on heparan sulfate proteoglycans and modulates multiple signaling pathways. It is normally bound to the cell surface but can be released into the medium of cultured cells. SULF2 is known to be increased in cirrhotic liver compared to healthy liver. We asked whether SULF2 protein was present in the blood of healthy controls and increased in patients with liver cirrhosis.', 'We devised a sandwich ELISA for SULF2 using 2 novel monoclonal antibodies (mAbs) and measured its levels in sera of normal individuals and cirrhosis patients.', 'SULF2 was higher in cirrhosis patients (1460 \u00b1 1160 pg/ml, N=34) than in healthy individuals (728 \u00b1 400 pg/ml, N=37). SULF2 levels increased with age in both healthy and patient groups.",
            "output": [
                "Is sULF2 , a heparan sulfate endosulfatase , present in the blood of healthy individuals and increases in cirrhosis?"
            ]
        },
        {
            "id": "task847-813ff2b57a854b2697d20e7cfd4a357d",
            "input": "Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation, extreme weight loss, and alterations in brain structure. Structural magnetic resonance imaging studies have documented brain volume reductions in acute AN, but it is unclear whether they are 1) regionally specific, or 2) reversible following weight restoration. Here, we measured cortical thickness (CT) for the first time in AN.', \"Structural magnetic resonance imaging data were acquired from adolescent and young adult female patients with acute AN (n = 40), recovered patients following long-term weight restoration (n = 34), and an equal number of age-matched healthy control subjects. Group differences in CT were tested with well-validated procedures implemented in FreeSurfer. The mediating role of clinical variables including body mass index and drive for thinness were explored. For completeness, we also used FreeSurfer's subcortical segmentation stream to test group differences in volumes of select gray matter regions of interest.\", 'Vertex-wise analyses revealed significant thinning of over 85% of the cortical surface in patients with acute AN and CT normalization in recovered patients following long-term weight restoration, although normal age-related trajectories were absent in the disorder. This pattern of results was largely mirrored in subcortical volumes. We also observed a strong negative correlation between CT and drive for thinness in extrastriate regions involved in body perception.",
            "output": [
                "Does global cortical thinning in acute anorexia nervosa normalize following long-term weight restoration?"
            ]
        },
        {
            "id": "task847-18895441fa44445c9dae155c2c494f08",
            "input": "Symptomatic patients with severe aortic stenosis (AS) demonstrate abnormal left ventricular (LV) mechanics. The aim of this study was to compare mechanics in asymptomatic and symptomatic patients with severe AS using two-dimensional myocardial strain imaging.', 'One hundred fifty-four patients with severe AS (aortic valve area \u2264 1.0 cm(2)) referred to a heart valve clinic from 2004 to 2011 were studied. Thirty patients were asymptomatic, with normal LV ejection fractions (\u2265 55%), without other significant valvular disease or wall motion abnormalities. Thirty-two symptomatic patients who underwent early aortic valve replacement, with similar age, gender, LV ejection fraction, and aortic valve area, were selected for comparison. Both groups were also compared with 32 healthy subjects with similar age and gender distributions and normal echocardiographic results who served as controls. LV longitudinal and circumferential strain and rotation were measured using speckle-tracking software applied to archived echocardiographic studies. Conventional echocardiographic and myocardial mechanical parameters were compared among the study subgroups.', 'Patients with asymptomatic severe AS demonstrated smaller reductions in longitudinal strain, higher (supernormal) apical circumferential strain (-38 \u00b1 6% vs -35 \u00b1 4%, P < .05), and extreme (supernormal) apical rotation (12.2 \u00b1 4.9\u00b0 vs 2.9 \u00b1 1.7\u00b0, P < .0005) compared with symptomatic patients. Apical rotation < 6\u00b0 was the single significant predictor of symptoms in logistic regression analysis of clinical, echocardiographic, and mechanical parameters. Twelve asymptomatic patients underwent eventual aortic valve replacement and showed decreases in strain and apical rotation compared with baseline values.",
            "output": [
                "Are symptoms in severe aortic stenosis associated with decreased compensatory circumferential myocardial mechanics?"
            ]
        },
        {
            "id": "task847-c89052c4471e4c70a932dfdce49d4362",
            "input": "Experimental animal studies provided evidence for a synergistic effect of immunological and psychological stressors on subsequent sickness behaviours. Up to now, little corroborating evidence for such synergy exists for humans, in whom it may provide a mechanism leading to the expression of functional somatic symptoms. The aim of the present study was to determine an interaction between stress(-vulnerability) and an immunological activation on experimental pain sensitivity, i.e., pressure pain threshold and tolerance in healthy humans.', 'In healthy female participants (n=25, mean age 22.3 years), negative affectivity (NA) and experienced stress were assessed by questionnaire before receiving a Salmonella typhi vaccine or saline control in a randomized blinded cross-over design. Pressure pain threshold was assessed at the lower back and calves and pain tolerance was assessed at the thumbnail, before and six hours after each injection.', 'Vaccination induced leukocytosis (+100%) and increased serum IL-6 (+670%). NA predicted decreased pain tolerance after vaccination (\u03b2=-.57, p=.007), but not after placebo (\u03b2=.25, p=.26). Post-hoc analyses also demonstrated an association with administration order.",
            "output": [
                "Does negative affectivity predict decreased pain tolerance during low-grade inflammation in healthy women?"
            ]
        },
        {
            "id": "task847-e6bc88f786ac4cba9b008337d13b93fc",
            "input": "To determine whether the presence of a capsule regulator gene [i.e., regulator of mucoid phenotype A (rmpA) gene] contributes to virulence on extended-spectrum \u03b2-lactamase-producing Klebsiella pneumoniae (ESBL-KP) with serotype non-K1/K2 strains.', 'Twenty-eight ESBL-KP and non-ESBL-KP isolates were collected from the Tri-Service General Hospital (Taipei, Taiwan). The impact of the virulent rmpA gene in different capsular polysaccharide serotypes on ESBL-KP and non-ESBL-KP isolates was studied by a neutrophil phagocytosis reaction, a serum bactericidal assay, and an animal survival model.', 'Resistance to broad spectrum antibiotics was more prevalent in ESBL-KP strains than in non-ESBL-KP strains (p\\xa0<\\xa00.01). The ESBL-KP strains had different molecular patterns from non-ESBL-KP strains, based on pulsed-field gel electrophoresis. The frequency of serum-resistant isolates was the highest among ESBL-KP strains with rmpA (i.e., rmpA(+)) [71.4% (5/7)] than among of non-ESBL-KP rmpA(+) strains [42.8% (6/14)], ESBL-KP strains without rmpA (rmpA(-)) [33.3% (7/21)], and non-ESBL-KP rmpA(-) strains [14.2% (2/14)]. The most significant increase in neutrophil resistance occurred in the ESBL-KP rmpA(+) strains in comparison to the non-ESBL-KP rmpA(+), ESBL-KP rmpA(-), and non-ESBL-KP rmpA(-) strains (p\\xa0<\\xa00.01). The results of the animal survival model were compatible with the neutrophil phagocytosis reaction and serum bactericidal assay.",
            "output": [
                "Does regulator of the mucoid phenotype A gene increase the virulent ability of extended-spectrum beta-lactamase-producing serotype non-K1/K2 Klebsiella pneumonia?"
            ]
        },
        {
            "id": "task847-061e12fc518b4f0fbe221adba6d56aef",
            "input": "To evaluate whether anxiety-prone rats exposed to chronic water avoidance stress (WAS) develop visceral bladder hyperalgesia in addition to increased voiding frequency and anxiety-related behaviors.', 'Female Wistar-Kyoto (WKY) rats were exposed to chronic (10-day) WAS or sham paradigms. Referred hyperalgesia and tactile allodynia were tested using von Frey filaments applied to the suprapubic region and plantar region of the hindpaw, respectively. To confirm that suprapubic nociception represented referred visceral bladder hyperalgesia, we recorded abdominal visceromotor responses (VMR) to slow (100 \u03bcl/min) and fast (1 cc/sec) bladder filling with room temperature or ice-cold saline. We assessed the development of hyperalgesia over the 10-day WAS protocol and the durability of increased pain sensations over time.', 'Animals exposed to chronic WAS had significantly lower hindpaw withdrawal thresholds post-stress and significant differences in referred hyperalgesia. Rats exposed to chronic WAS demonstrated an increased pain response to suprapubic stimulation and decreased response threshold to mechanical hindpaw stimulation by day 8 of the stress protocol, which persisted for more than one month. Animals exposed to chronic WAS showed increased VMR to fast filling and ice water testing in comparison to sham animals. Cystometry under anesthesia did not show increases in the frequency of non-voiding contractions.",
            "output": [
                "Does chronic psychological stress in high-anxiety rats induce sustained bladder hyperalgesia?"
            ]
        },
        {
            "id": "task847-364db03ddd76407bb6d833b7c244f95f",
            "input": "Epidemiologic evidence suggests a link between short sleep duration and cardiovascular risk, although the nature of any relationship and mechanisms remain unclear. Short sleep duration has also been linked to an increase in cardiovascular events. Endothelial dysfunction has itself been implicated as a mediator of heightened cardiovascular risk. We sought to determine the effect of 8 days/8 nights of partial sleep restriction on endothelial function in healthy humans.', 'Sixteen healthy volunteers underwent a randomized study of usual sleep versus sleep restriction of two-thirds normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcome was endothelial function measured by flow-mediated brachial artery vasodilatation (FMD). Those randomized to sleep restriction slept 5.1 hours/night during the experimental period compared with 6.9 hours/night in the control group. Sleep restriction was associated with significant impairment in FMD (8.6\u00b14.6% during the initial pre-randomization acclimation phase versus 5.2\u00b13.4% during the randomized experimental phase, P=0.01) whereas no change was seen in the control group (5.0\u00b13.0 during the acclimation phase versus 6.73\u00b12.9% during the experimental phase, P=0.10) for a between-groups difference of -4.40% (95% CI -7.00 to -1.81%, P=0.003). No change was seen in non-flow mediated vasodilatation (NFMD) in either group.",
            "output": [
                "Does experimental sleep restriction cause endothelial dysfunction in healthy humans?"
            ]
        },
        {
            "id": "task847-2eee27839e994dd491eb90a3ca21d2d0",
            "input": "Chronic pancreatitis is characterized by inflammation, atrophy, fibrosis with progressive ductal changes, and functional changes that include variable exocrine and endocrine insufficiency and multiple patterns of pain. We investigated whether abdominal imaging features accurately predict patterns of pain.', 'We collected data from participants in the North American Pancreatitis Study 2 Continuation and Validation, a prospective multicenter study of patients with chronic pancreatitis performed at 13 expert centers in the United States from July 2008 through March 2012. Chronic pancreatitis was defined based on the detection of characteristic changes by cross-sectional abdominal imaging, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, or histology analyses. Patients were asked by a physician or trained clinical research coordinator if they had any abdominal pain during the year before enrollment, those who responded \"yes\" were asked to select from a list of 5 pain patterns. By using these patterns, we\\xa0classified patients\\' pain based on timing and severity. Abnormal pancreatitis-associated features on abdominal imaging were recorded using standardized case report forms.', 'Data were collected from 518 patients (mean age, 52 \u00b1 14.6 y; 55% male; and 87.6% white). The most common physician-identified etiologies were alcohol (45.8%) and idiopathic (24.3%); 15.6% of patients reported no abdominal pain in the year before enrollment. The most common individual pain pattern was described as constant mild pain with episodes of severe pain and was reported in 45% of patients. The most common imaging findings included pancreatic ductal dilatation (68%), atrophy (57%), and calcifications (55%). Imaging findings were categorized as obstructive for 20% and as inflammatory for 25% of cases. The distribution of individual imaging findings was similar among patients with different patterns of pain. The distribution of pain patterns did not differ among clinically relevant groups of imaging findings.",
            "output": [
                "Are chronic pancreatitis pain pattern and severity independent of abdominal imaging findings?"
            ]
        },
        {
            "id": "task847-640dd80a631241399d7abc1c6efc1bf3",
            "input": "To investigate the influence of different phlebotomy postures on clinical chemistry testing.', 'Nineteen volunteers were recruited from the laboratory staff. A first set of samples was drawn after 25 min of resting in supine position, a second after 20 min in sitting position, and a third after 20 min in upright position. Clinical chemistry testing was performed on Roche Cobas C501.', 'The plasma volume change (PVC) was -3.4% from supine to sitting, -14.1% from supine to standing and -9.7% from sitting to standing. Compared to quality specifications for bias, hemoglobin, hematocrit, albumin and total proteins exhibited meaningful increases from supine to sitting, whereas meaningful increases were observed for hemoglobin, hematocrit, albumin, alkaline phosphatase (ALP), amylase, aspartate aminotransferase (AST), total bilirubin, calcium, total and high-density lipoprotein (HDL) cholesterol, gamma-glutamyl transferase (GGT), glucose, lactate dehydrogenase (LDH), magnesium, total protein and triglycerides from sitting to standing. The parameters with meaningful bias from sitting to upright were hemoglobin, hematocrit, albumin, ALP, total bilirubin, calcium, total and HDL cholesterol, glucose, LDH and total protein.",
            "output": [
                "Is postural change during venous blood collection a major source of bias in clinical chemistry testing?"
            ]
        },
        {
            "id": "task847-ddebc4a9cb76416fa37a863b0bbddfa9",
            "input": "Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age.', 'This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced.', 'This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed.",
            "output": [
                "Are novel mutations in the displacement loop of mitochondrial DNA associated with acute lymphoblastic leukemia : a genetic sequencing study?"
            ]
        },
        {
            "id": "task847-beba84910bee46ffb789b078f5dda3b8",
            "input": "Construction of electrochemical impedance sensors by the self-assembly technique has become a promising strategy for the 'label-free' detection of protein-ligand interactions. However, previous impedance sensors are devoid of an inherent electrochemical signal, which limits the standardization of the sensors for protein recognition in a reproducible manner.\", \"We designed and synthesized an anthraquinonyl glycoside (AG) where the anthraquinone (AQ) moiety can bind to the surface of a graphene-based working electrode while the glycoside serving as a ligand for lectin. By measuring the inherent voltammetric signal of AQ, the glycosides decorated on the working electrode could be simply quantified to obtain electrodes with a unified signal window. Subsequently, impedance analysis showed that the 'standardized' electrodes gave a reproducible electrochemical response to a selective lectin with no signal variation in the presence of unselective proteins.",
            "output": [
                "Does anthraquinonyl glycoside facilitate the standardization of graphene electrodes for the impedance detection of lectins?"
            ]
        },
        {
            "id": "task847-bd6c8942123b4590877511a53ac995ec",
            "input": "The aim of this study is to assess the usefulness of perfusion computer tomography (pCT) in prostate cancer (PCa) diagnostics.', '94 patients with biopsy-proven PCa were enrolled in the study. Dynamic pCT of the prostate gland was performed for 50 seconds after an intravenous injection of contrast medium. Blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were computed in the suspected PCa area and in normal prostatic tissue.', 'PCa was visible in pCT in 90 of the 94 examined patients as a focal peripheral CT enhancement. When PCa was located in the peripheral zone (PZ), it was visible on perfusion maps, mostly showing an early peak followed by wash-out. The average values of all perfusion parameters were higher for tumour than for normal prostate tissue (p < 0.000). BV and BF were dependent on tumour grade expressed by the Gleason score (GS). All PCa cases were divided into groups, according to histological grade, as low (GS \u2264 6), medium (GS = 7), and high (GS > 7). In high-grade PCa, the mean BF value was significantly higher (p = 0.001) than the mean value of BF low- and medium-grade PCa (p = 0.011). Similar results were obtained regarding the mean values of BV; the more aggressive the cancer grade, the higher the mean BV value (p = 0.04).",
            "output": [
                "Is perfusion CT a valuable diagnostic method for prostate cancer : a prospective study of 94 patients?"
            ]
        },
        {
            "id": "task847-870ab068265d437ba9c603cd25f4f6b7",
            "input": "High tumor interstitial fluid pressure (IFP) is associated with poor outcome in locally advanced carcinoma of the uterine cervix. We have recently developed a noninvasive assay of the IFP of tumors, and in this assay, the outward interstitial fluid flow velocity at the tumor surface (v0) is measured by Gd-DTPA-based DCE-MRI and used as a parameter for IFP. Here, we investigated the independent prognostic significance of v0 in cervical cancer patients given cisplatin-based concurrent chemoradiotherapy with curative intent.', 'The study involved 62 evaluable patients from a cohort of 74 consecutive patients (Stage IB through IIIB) with a median follow-up of 5.5 years.', 'The actuarial disease-free survival (DFS) and overall survival (OS) at 5 years were 67% and 76%, respectively. Significant associations were found between v0 dichotomized about the median value and DFS and OS, both in the total patient cohort and a subcohort of 40 Stage IIB patients. Multivariate analysis involving stage, tumor volume, lymph node status, and v0 revealed that only v0 provided independent prognostic information about DFS and OS.",
            "output": [
                "Does peritumoral interstitial fluid flow velocity predict survival in cervical carcinoma?"
            ]
        },
        {
            "id": "task847-a96f9248647a4eb38839e2b64f858cfe",
            "input": "When medical students move from the classroom into clinical practice environments, their roles and learning challenges shift dramatically from a formal curricular approach to a workplace learning model. Continuity among peers during clinical clerkships may play an important role in this different mode of learning. We explored students' perceptions about how they achieved workplace learning in the context of intentionally formed or ad hoc peer groups.\", \"We invited students in clerkship program models with continuity (CMCs) and in traditional block clerkships (BCs) to complete a survey about peer relationships with open-ended questions based on a workplace learning framework, including themes of workplace-based relationships, the nature of work practices, and selection of tasks and activities. We conducted qualitative content analysis to characterize students' experiences.\", 'In both BCs and CMCs, peer groups provided rich resources, including anticipatory guidance about clinical expectations of students, best practices in interacting with patients and supervisors, helpful advice in transitioning between rotations, and information about implicit rules of clerkships. Students also used each other as benchmarks for gauging strengths and deficits in their own knowledge and skills.",
            "output": [
                "Do workplace learning through peer groups in medical school clerkships?"
            ]
        },
        {
            "id": "task847-be96d82584dc408581943a70ff8cf10b",
            "input": "Tourette syndrome (TS) is characterized by a wide phenotypic polymorphism and this heterogeneity is due partly to the association with several neuropsychiatry disorders. These comorbidities are showed in the 90% of TS cases. The aim of this transversal study is to analyze the presence and prevalence of different psychopathological conditions that could be expressed with tic disorder (TD) and specifically in TS.', 'We examined a sample of 102 patients, between 7 and 17.6 years old, with a diagnosis DSM-IV-TR of TD, using the self-report SAFA.', 'Different correlations between these comorbidities and clinical variables are also analyzed. Our data underlined most of all a prevalence of anxiety disorders in the 31.4% of our patients with TD, of depression in the 27.44%, and of somatization symptoms in the 22.54%.",
            "output": [
                "Does [ Prevalence of anxiety disturb in patients with Tourette syndrome and tic disturb ]?"
            ]
        },
        {
            "id": "task847-beea487b6b50485a9515ea9e0f35d255",
            "input": "Accurate diagnosis of egg allergy by IgE testing is challenged by a large number of atopic subjects sensitized, but clinically tolerant to eggs. In addition, discrimination between allergy to raw only, or raw and cooked egg allergy is important. In this study, we investigate the diagnostic performance of IgE tests to native and denatured egg proteins.', 'According to food challenges and clinical tolerance, study subjects were randomized to the following groups: (Group A) sensitized but clinically tolerant to egg, (Group B) allergic to raw egg only, or (Group C) allergic to raw and cooked egg. Serum-specific IgE to native or reduced and oxidized egg white, ovomucoid, and ovalbumin were measured.', 'Increasing titers of specific IgE to the various proteins were found according to the degree of the egg allergy. Cut-off values for IgE testing to native egg could be determined to distinguish between raw egg allergic and egg-tolerant subjects (1.6 kU/l), as well as raw and cooked egg allergic and egg-tolerant subjects (4.1 kU/l). ROC curves analysis showed that native ovalbumin was the best test for the diagnosis of allergy to raw and cooked egg, and native ovomucoid was best to distinguish between allergy to raw only, and allergy to raw and cooked egg. Sequential testing improved the diagnosis, when in addition to IgE to native egg white, IgE to native ovalbumin was tested for the diagnosis of raw and cooked egg allergy, and IgE to native ovomucoid for the discrimination between allergy to raw only, or to raw and cooked eggs.",
            "output": [
                "Do native and denatured egg white protein IgE tests discriminate hen 's egg allergic from egg-tolerant children?"
            ]
        },
        {
            "id": "task847-59cd80d5f9d74b0585b555d392acae9c",
            "input": "Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier. Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity. In chronic obstructive pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling. The objective was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.', 'Patients scheduled for lung resection were prospectively recruited. Demographic, clinical data and pulmonary function tests results were recorded. Emphysema was visually scored and histological remodeling features were noted. Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay. We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease (MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding. In a subset of patients, bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.', '13 COPD and 7 non COPD patients were included. The severity of airflow obstruction and the severity of emphysema were associated with a lower MSWC in BEC (p = 0.01, 95% CI [0.15-0.80]; p = 0.04, 95% CI [-0.77;-0.03] respectively). Cell proliferation index was decreased in COPD patients (19 \u00b1 6% in COPD vs 27 \u00b1 3% in non COPD, p = 0.04). The severity of COPD was associated with a lower level of MMP-2 (7.8 \u00b1 2 10(5) AU in COPD GOLD D vs 12.8 \u00b1 0.13 10(5) AU in COPD GOLD A, p = 0.04) and a lower level of IL-4 (p = 0.03, 95% CI [0.09;0.87]). Moreover, higher levels of IL-4 and IL-2 were associated with a higher MSWC (p = 0.01, 95% CI [0.17;0.89] and p = 0.02, 95% CI [0.09;0.87] respectively). Clinical characteristics and smoking history were not associated with MSWC, cell proliferation index or MMP and cytokines levels. Finally, we showed an association of the MSWC of bronchial and corresponding bronchiolar epithelial cells obtained from the same patients (p = 0.02, 95% CI [0.12;0.89]).",
            "output": [
                "Is delay of airway epithelial wound repair in COPD associated with airflow obstruction severity?"
            ]
        },
        {
            "id": "task847-6e4a76a2a5cd4a4b8c5e1340d097dadf",
            "input": "Stressors negatively impact emotional state and drive drug seeking, in part, by modulating the activity of the mesolimbic dopamine system. Unfortunately, the rapid regulation of dopamine signaling by the aversive stimuli that cause drug seeking is not well characterized. In a series of experiments, we scrutinized the subsecond regulation of dopamine signaling by the aversive stimulus, quinine, and tested its ability to cause cocaine seeking. Additionally, we examined the midbrain regulation of both dopamine signaling and cocaine seeking by the stress-sensitive peptide, corticotropin releasing factor (CRF).', 'Combining fast-scan cyclic voltammetry with behavioral pharmacology, we examined the effect of intraoral quinine administration on nucleus accumbens dopamine signaling and hedonic expression in 21 male Sprague-Dawley rats. We tested the role of CRF in modulating aversion-induced changes in dopamine concentration and cocaine seeking by bilaterally infusing the CRF antagonist, CP-376395, into the ventral tegmental area (VTA).', 'We found that quinine rapidly reduced dopamine signaling on two distinct time scales. We determined that CRF acted in the VTA to mediate this reduction on only one of these time scales. Further, we found that the reduction of dopamine tone and quinine-induced cocaine seeking were eliminated by blocking the actions of CRF in the VTA during the experience of the aversive stimulus.",
            "output": [
                "Do aversive stimuli drive drug seeking in a state of low dopamine tone?"
            ]
        },
        {
            "id": "task847-3254ebaad9cd444388378915b41be762",
            "input": "It is common in public health and epidemiology that the outcome of interest is counts of events occurrence. Analysing these data using classical linear models is mostly inappropriate, even after transformation of outcome variables due to overdispersion. Zero-adjusted mixture count models such as zero-inflated and hurdle count models are applied to count data when over-dispersion and excess zeros exist. Main objective of the current paper is to apply such models to analyse risk factors associated with human helminths (S. haematobium) particularly in a case where there's a high proportion of zero counts.\", 'The data were collected during a community-based randomised control trial assessing the impact of mass drug administration (MDA) with praziquantel in Malawi, and a school-based cross sectional epidemiology survey in Zambia. Count data models including traditional (Poisson and negative binomial) models, zero modified models (zero inflated Poisson and zero inflated negative binomial) and hurdle models (Poisson logit hurdle and negative binomial logit hurdle) were fitted and compared.', 'Using Akaike information criteria (AIC), the negative binomial logit hurdle (NBLH) and zero inflated negative binomial (ZINB) showed best performance in both datasets. With regards to zero count capturing, these models performed better than other models.",
            "output": [
                "Do zero adjusted models with applications to analysing helminths count data?"
            ]
        },
        {
            "id": "task847-feb547f711f4458687b4c37f1ee81b51",
            "input": "Induced aboveground plant defenses against pathogens can have negative effects on belowground microbial symbionts. While a considerable number of studies have utilized chemical elicitors to experimentally induce such defenses, there is surprisingly little evidence that actual aboveground pathogens affect root-associated microbes. We report here that an aboveground fungal pathogen of common bean (Phaseolus vulgaris) induces a defense response that inhibits both the belowground formation of root nodules elicited by rhizobia and the colonization with arbuscular mycorrhizal fungi (AMF).', 'Foliage of plants inoculated with either rhizobia or AMF was treated with both live Colletotrichum gloeosporioides-a generalist hemibiotrophic plant pathogen-and C. gloeosporioides fragments. Polyphenol oxidase (PPO), chitinase and \u03b2-1,3-glucanase activity in leaves and roots, as well as the number of rhizobia nodules and the extent of AMF colonization, were measured after pathogen treatments. Both the live pathogen and pathogen fragments significantly increased PPO, chitinase and \u03b2-1,3-glucanase activity in the leaves, but only PPO activity was increased in roots. The number of rhizobia nodules and the extent of AMF colonization was significantly reduced in treatment plants when compared to controls.",
            "output": [
                "Does an aboveground pathogen inhibit belowground rhizobia and arbuscular mycorrhizal fungi in Phaseolus vulgaris?"
            ]
        },
        {
            "id": "task847-8675f16a462a4ac1b018eb47af102b0f",
            "input": "Migraine headache is one of the most common primary headache disorders and is three times more prevalent in women than in men, especially during the reproductive ages. The neurobiological basis of the female dominance has been partly established. The present study aimed to investigate the effect of gender on the headache manifestations in migraine patients.', \"The study group consisted of 2082 adult patients from five different hospitals' tertiary care-based headache clinics. The relationship between headache characteristics and gender was evaluated in migraine with aura (MwA) and migraine without aura (MwoA). The duration, severity, frequency of headache and associated symptoms were evaluated in both genders and age-dependent variations and analyzed in two subgroups.\", 'Women with migraine were prone to significantly longer duration and intensity of headache attacks. Nausea, phonophobia and photophobia were more prevalent in women. Median headache duration was also longer in women than in men in MwA (p\\u2009=\\u20090.013) and MwoA (p\\u2009<\\u20090.001). Median headache intensity was higher in women than in men in MwA (p\\u2009=\\u20090.010) and MwoA (p\\u2009=\\u20090.009). The frequency of nausea was significantly higher in women than in men in MwA (p\\u2009=\\u20090.049). Throbbing headache quality and associated features (nausea, photophobia, and phonophobia) were significantly more frequent in women than in men in MwoA. The gender impact varied across age groups and significant changes were seen in female migraineurs after age 30. No age-dependent variation was observed in male migraineurs.",
            "output": [
                "Does gender influence headache characteristics with increasing age in migraine patients?"
            ]
        },
        {
            "id": "task847-66bf781b9b9a4e2d9c60eee20aa03888",
            "input": "This large cross-sectional, multi-centre study evaluated the association of body composition measurements by a novel dual frequency bioimpedance device (BIA-ACC) with chronic stress/inflammation biomarkers and the presence of medically unexplained symptoms (MUS).', 'Participants were adult Caucasians of both sexes and included 10,416 lean subjects with no MUS (Group A), 58,710 lean subjects with MUS (Group B) and 30,445 overweight/obese subjects with no MUS and excessive fat mass (FM) (Group C).', 'Total body extracellular water (ECW) was higher, while intracellular water (ICW) was lower in Group B than both other groups (P < 0.01). Group A had significantly lower FM and higher skeletal mass (SK) and phase angle (PA) than Group B and lower circulating high sensitivity (hs) CRP levels than both other groups. hsCRP was higher in Group C than Group A though (P < 0.01). Salivary cortisol in Group B was lower in the morning and higher in the evening than both other groups (P < 0.001), indicating circadian rhythm obliteration or reversal in this group. ECW correlated positively with serum hsCRP and 8 p.m. salivary cortisol, but negatively with 8 a.m. salivary cortisol, while PA correlated positively with 8 a.m. and negatively with 8 p.m. salivary cortisol and serum hsCRP. Both 8 a.m. and 8 p.m. salivary cortisol and serum hsCRP were associated with the presence of MUS and BIA-ACC measurements, including ECW, ICW, FM, SK and PA.",
            "output": [
                "Are stress and inflammatory biomarkers and symptoms associated with bioimpedance measures?"
            ]
        },
        {
            "id": "task847-0f2f04eefbb1411baf4f2d25ed78e7bb",
            "input": "The P301S mutation in exon 10 of the tau gene causes a hereditary tauopathy. While mitochondrial complex I inhibition has been linked to sporadic tauopathies. Piericidin A is a prototypical member of the group of the piericidins, a class of biologically active natural complex I inhibitors, isolated from streptomyces spp. with global distribution in marine and agricultural habitats. The aim of this study was to determine whether there is a pathogenic interaction of the environmental toxin piericidin A and the P301S mutation.', 'Transgenic mice expressing human tau with the P301S-mutation (P301S+/+) and wild-type mice at 12 weeks of age were treated subcutaneously with vehicle (N\\u200a=\\u200a10 P301S+/+, N\\u200a=\\u200a7 wild-type) or piericidin A (N\\u200a=\\u200a9 P301S+/+, N\\u200a=\\u200a9 wild-type mice) at a dose of 0.5 mg/kg/d for a period of 28 days via osmotic minipumps. Tau pathology was measured by stereological counts of cells immunoreative with antibodies against phosphorylated tau (AD2, AT8, AT180, and AT100) and corresponding Western blot analysis.', 'Piericidin A significantly increased the number of phospho-tau immunoreactive cells in the cerebral cortex in P301S+/+ mice, but only to a variable and mild extent in wild-type mice. Furthermore, piericidin A led to increased levels of pathologically phosphorylated tau only in P301S+/+ mice. While we observed no apparent cell loss in the frontal cortex, the synaptic density was reduced by piericidin A treatment in P301S+/+ mice.",
            "output": [
                "Does piericidin A aggravate Tau pathology in P301S transgenic mice?"
            ]
        },
        {
            "id": "task847-bfa73a1beb7741f5ab13c05a6aa9c490",
            "input": "Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated.', 'We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies.",
            "output": [
                "Are cognitive-behavioral phenotypes of Williams syndrome associated with genetic variation in the GTF2I gene , in a healthy population?"
            ]
        },
        {
            "id": "task847-4d010423d5b5488185d6f93be43ea884",
            "input": "Hypertension and obesity are highly prevalent in Western societies. We investigated the associations of changes in body weight with changes in blood pressure and with incident hypertension, incident cardiovascular events, or incident normalization of blood pressure in patients who were hypertensive at baseline, over a 5-year period.', 'Data of men and women aged 20-81 years of the Study of Health in Pomerania were used. Changes in body weight were related to changes in blood pressure by linear regression (n = 1875) adjusted for cofounders. Incident hypertension, incident cardiovascular events, or incident blood pressure normalization in patients who were hypertensive at baseline were investigated using Poisson regression (n = 3280) models. A change of 1 kg in body weight was positively associated with a change of 0.45 mm Hg (95% confidence interval (CI): 0.34-0.55 mm Hg) in systolic blood pressure, 0.32 mm Hg (95% CI: 0.25-0.38 mm Hg) in diastolic blood pressure, and 0.36 mm Hg (95% CI: 0.29-0.43 mm Hg) in mean arterial pressure (all p-values <0.001). A 5% weight loss reduced the relative risk (RR) of incident hypertension (RRs 0.84 (95% CI: 0.79-0.89)) and incident cardiovascular events (RRs 0.81 (95% CI: 0.68-0.98)) and increased the chance of incident blood pressure normalization in patients who were hypertensive at baseline by 15% (95% CI: 7-23%).",
            "output": [
                "Are long-term changes in body weight associated with changes in blood pressure levels?"
            ]
        },
        {
            "id": "task847-26db545b984242e38eff5017be9d3a54",
            "input": "Previous studies have proved the feasibility of performing a pancreaticoduodenectomy (Whipple operation) in patients with portal vein-superior mesenteric vein and hepatic artery invasion. We report our institutional experience with the use of a variety of vascular reconstructive methods during pancreatic resections for adenocarcinoma.', 'A retrospective review was performed identifying all patients undergoing a Whipple operation or total pancreatectomy procedure from January 2003 to December 2013. All venous (portal vein-superior mesenteric vein) and arterial (superior mesenteric artery-hepatic artery) reconstructions were extracted and reviewed to determine survival and perioperative complications.', 'During the 10-year study period, 270 Whipple and total pancreatectomy procedures were performed, of which 183 were for adenocarcinoma of the pancreas. Of the 183 operations, a total of 60 (32.8%) vascular reconstructions were found, 49 venous and 11 arterial. Venous reconstruction included 37 (61.7%) primary repairs, four (6.7%) reconstructions with CryoVein (CryoLife, Inc, Kennesaw, Ga), three (5.0%) repairs with autologous vein patch, three (5.0%) autologous saphenous reconstructions, and two (3.33%) portacaval shunts. In addition, there were 11 (18.3%) arterial reconstructions (seven hepatic artery and four superior mesenteric artery). The 1-year survival for all reconstructions was 71.1%, which is equivalent to T3 lesions that did not receive vascular reconstruction (70.11%), with a median survival time of 575.28 days and 12 patients still alive. Survival time was comparable with each type of venous reconstruction, averaging 528 days (11 of 49 patients still alive). There was a total thrombosis rate of seven of 60 (11.6%), all of which were portal vein thrombosis: three in the primary repair group and four delayed thromboses seen in primary repair, CryoVein repair, and vein patch repair. There was no thrombosis in any patients after arterial reconstruction.",
            "output": [
                "Does vascular reconstruction play an important role in the treatment of pancreatic adenocarcinoma?"
            ]
        },
        {
            "id": "task847-e075199aed3b48df92be9d2069149c2f",
            "input": "Peripheral arterial disease (PAD) is associated with poor prognosis in terms of cardiovascular (CV) morbidity and mortality. Matrix metalloproteinases (MMPs) contribute to vascular remodeling by degrading extracellular matrix components and play a role in atherosclerosis as demonstrated for MMP-10 (stromelysin-2). This study analyzed MMP-10 levels in PAD patients according to disease severity and CV risk factors and evaluated the prognostic value of MMP-10 for CV events and mortality in lower limb arterial disease after a follow-up period of 2 years.', 'MMP-10 was measured by enzyme-linked immunosorbent assay in 187 PAD patients and 200 sex-matched controls.', 'PAD patients presented with increased levels of MMP-10 (702 \u00b1 326 pg/mL control vs 946 \u00b1 473 pg/mL PAD; P < .001) and decreased levels of tissue inhibitor of matrix metalloproteinase 1 (312 \u00b1 117 ng/mL control vs 235 \u00b1 110 ng/mL PAD; P < .001) compared with controls. Among PAD patients, those with critical limb ischemia (n = 88) showed higher levels of MMP-10 (1086 \u00b1 478 pg/mL vs 822 \u00b1 436 pg/mL; P < .001) compared with those with intermittent claudication (n = 99), whereas the MMP-10/tissue inhibitor of matrix metalloproteinase 1 ratio remained similar. The univariate analysis showed an association between MMP-10, age (P = .015), hypertension (P = .021), and ankle-brachial index (P = .006) in PAD patients that remained significantly associated with PAD severity after adjustment for other CV risk factors. Patients with the highest MMP-10 tertile had an increased incidence of all-cause mortality and CV mortality (P < .03).",
            "output": [
                "Is matrix metalloproteinase 10 associated with disease severity and mortality in patients with peripheral arterial disease?"
            ]
        },
        {
            "id": "task847-65ff7a3013a94487a4066db72445d493",
            "input": "Extracorporeal circulation is routinely used in thoracoabdominal aortic aneurysm repair to preserve blood perfusion. Despite this protective measure, acute and chronic kidney disorders can develop. Therefore, the aim of this study was to establish a new large-animal model to assess the efficacy of selective renal perfusion (SRP) with extracorporeal circulation in a setting of thoracoabdominal aortic aneurysm repair.', 'Eighteen pigs underwent a thoracolaparotomy, during with the aorta and renal arteries were exposed. The animals were divided into three cohorts of six pigs each: cohort I--control; cohort II--thoracic aortic clamping with distal aortic perfusion (DAP) using a roller pump; and cohort III--thoracic aortic clamping with DAP plus SRP. Kidney metabolism, kidney injury, and red blood cell damage were measured by oxygen extraction ratio (O2ER), neutrophil gelatinase-associated lipocalin, a marker for acute kidney damage, and serum free hemoglobin.', 'With normal mean arterial blood pressures, flow rates in the renal arteries during perfusion decreased to 75% (group II) with DAP and to 50% (group III) with SRP compared with the control animals (group I; P = .0279 for I vs II; P = .0002 for I vs III). Microcirculation, measured by microspheres, did not differ significantly among the groups. In contrast, O2ER (P = .0021 for I vs III) and neutrophil gelatinase-associated lipocalin (P = .0083 for I vs III) levels were significantly increased in group III, whereas free hemoglobin was increased in groups II and III (P = .0406 for I vs II; P = .0018 for I vs III).",
            "output": [
                "Does selective renal blood perfusion induce renal tubules injury in a porcine model?"
            ]
        },
        {
            "id": "task847-9ecd38af63a34a06b726f3613434984a",
            "input": "To evaluate whether P2X3 receptors (P2X3R) are expressed in the bladder urothelium and to determine their possible function in modulating purinergic detrusor contractions in the rat urinary bladder.', 'The expression of urothelial receptors was determined using conventional immunohistochemistry in bladders from normal Sprague-Dawley rats. The urothelial layer was removed by incubation with protamine, and disruption of the urothelium was confirmed using haematoxylin and eosin staining on bladder sections. Open cystometry was used to determine the effects of both urothelial removal as well as intravesical application of a specific P2X3R antagonist on bladder properties from intact and protamine-treated rats. Isometric contractile responses to potassium chloride (KCl) depolarization, electrical field stimulation (EFS) or chemical P2X activation were determined in normal and urothelium-denuded bladder strips, with and without application of the P2X3R antagonist.', 'Immunohistochemical staining showed high expression of P2X3R in the medial and basal layers of the urothelium. Removal of the urothelial layer disturbed normal bladder performance in vivo and eliminated the effects of the P2X3R antagonist on increasing the contractile interval and reducing the amplitude of voiding contractions. Removal of the urothelium did not affect bladder strip contractile responses to KCl depolarization or EFS. Pharmacological inhibition of P2X3R prevented desensitization to P2X-mediated detrusor muscle contractions during EFS only in the strips with an intact urothelium. A concentration-dependent, specific inhibition of P2X3R also prevented desensitization of purinergic contractile responses in intact bladder strips.",
            "output": [
                "Does inhibition of urothelial P2X3 receptors prevent desensitization of purinergic detrusor contractions in the rat bladder?"
            ]
        },
        {
            "id": "task847-da26c207c07145ed9d1ef51417d42e9d",
            "input": "Decreases in mate and/or pollinator availability would be expected to affect the selective pressure on plant mating systems. An increase in self-fertilization may evolve to compensate for the negative effects of pollination failure. However, the benefit of selfing in variable pollination environments depends on the relative fitnesses of selfed and outcrossed progeny. We investigated the potential for selfing to provide reproductive assurance over the lifetime of a long-lived perennial species and its variation between plant patches of various sizes. Patch size is likely to affect mate and pollinator availabilities, thereby affecting pollination success and the rate of selfing. We estimated fruit and seed set, reproductive assurance, self-compatibility, the multilocus patch selfing rate and lifetime inbreeding depression in natural patches of Rhododendron ferrugineum (Ericaceae), a mass-flowering species characterized by considerable patch size variation (as estimated by the total number of inflorescences).', 'Open seed set declined linearly with increasing patch size, whereas pollinator-mediated seed set (emasculated flowers) was not significantly affected. Progeny array analysis indicated that the selfing rate declined with increasing patch size, consistent with greater reproductive assurance in small sparse patches than in large, dense patches. However, fruit set and adult fitness decreased with decreasing patch size, with an estimated mean lifetime inbreeding depression of 0.9 (obtained by comparing F values in adults and progenies).",
            "output": [
                "Does high lifetime inbreeding depression counteract the reproductive assurance benefit of selfing in a mass-flowering shrub?"
            ]
        },
        {
            "id": "task847-dbda36f5dc7544719349ebaf304063fc",
            "input": "Antibody-mediated rejection (ABMR) is dependent on complement activating donor-specific anti-HLA antibodies (DSA). This is commonly detected by C4d deposition in allografts. However, recent data define a C4d negative ABMR phenotype suggesting a role for complement-independent DSA injury, antibody-dependent cellular cytotoxicity (ADCC).', 'Here, we established an in vitro ADCC model that identified human ADCC-activated genes using microarray analysis. We subsequently interrogated renal allograft biopsies from patients with ABMR and controls for mRNA expression of the ADCC-activated gene set.', 'We identified 13 ADCC-activated genes. Six gene expression assays including 8 of the 13 genes (CCL3, CCL4/CCL4L1/CCL4L2, CD160, IFNG, NR4A3 and XCL1/XCL2) were analyzed in 127 kidney biopsies obtained from HLA-sensitized (HS), non-HS patients and control individuals. Most ADCC-activated genes showed significantly higher expression in the transplant samples compared to the controls (p<0.0005). The gene expression levels were significantly higher in HS and non-HS transplant patients who developed ABMR compared to those who did not (p=0.04-0.002). There was no difference in the gene expression levels between C4d positive and negative ABMR (p=0.26-0.99). Samples from high PRA (>80%) or positive DSA patients showed higher gene expression levels for the ADCC-activated genes compared to low PRA (<80%) and negative DSA patients (p=0.04-0.001).",
            "output": [
                "Are genes associated with antibody-dependent cell activation overexpressed in renal biopsies from patients with antibody-mediated rejection?"
            ]
        },
        {
            "id": "task847-c5c88d5442e1483f9bcc524a677f53ae",
            "input": "Optical techniques are routinely used to size and count extracellular vesicles (EV). For comparison of data from different methods and laboratories, suitable calibrators are essential. A suitable calibrator must have a refractive index (RI) as close to that of EV as possible but the RI of EV is currently unknown. To measure EV, RI requires accurate knowledge of size and light scattering. These are difficult to measure as most EVs cannot be resolved by light microscopy and their diameter is smaller than the wavelength of visible light. However, nanoparticle tracking analysis (NTA) provides both size and relative light scattering intensity (rLSI) values. We therefore sought to determine whether it was possible to use NTA to measure the RI of individual EVs.', 'NTA was used to measure the rLSI and size of polystyrene and silica microspheres of known size and RI (1.470 and 1.633, respectively) and of EV isolated from a wide range of cells. We developed software, based on Mie scattering code, to calculate particle RI from the rLSI data. This modelled theoretical scattering intensities for polystyrene and silica microspheres of known size (100 and 200 nm) and RI. The model was verified using data from the polystyrene and silica microspheres. Size and rLSI data for each vesicle were processed by the software to generate RI values.', 'The following modal RI measurements were obtained: fresh urinary EV 1.374, lyophilised urinary EV 1.367, neuroblastoma EV 1.393, blood EV 1.398, EV from activated platelets 1.390, small placental EV 1.364-1.375 and 1.398-1.414 for large placental EV (>200 nm). Large placental EV had a significantly higher RI than small placental EV (p<0.0001). The spread of RI values was narrower for small EV than for the more heterogeneous large EV.",
            "output": [
                "Does measurement of refractive index by nanoparticle tracking analysis reveal heterogeneity in extracellular vesicles?"
            ]
        },
        {
            "id": "task847-96c5b66a50e24ac0a4ca5816e4048397",
            "input": "To incorporate C-reactive protein into nomograms estimating survival in patients with renal cell carcinoma.', 'Patients undergoing surgery for renal cell carcinoma from 2005-2012 were studied retrospectively. Multivariable Cox proportional hazards regression and competing risks regression models including stage, grade, C-reactive protein levels and presence of metastatic disease were constructed. Outcomes analyzed include overall mortality overall mortality and renal cell carcinoma-specific mortality.', 'The cohort included 516 patients with a mean follow up of 1.7\\u2009years (SD 1.4\\u2009years). One- and 3-year renal cell carcinoma-specific mortality was 8.8% and 13.5%, respectively. Four nomograms were generated using overall mortality and renal cell carcinoma-specific mortality as end-points, two each for pre- and postoperative counseling. The factor with the largest effect on all nomograms was preoperative C-reactive protein. Based on the internal validation with bootstrapping, the concordance indices for renal cell carcinoma-specific mortality in the preoperative nomogram, postoperative nomogram, and the Mayo Clinic stage, size, grade and necrosis score were 0.889, 0.893, and 0.832, respectively (P\\u2009=\\u20090.005 and 0.002 comparing with stage, size, grade and necrosis scores for preoperative or postoperative nomograms). For overall mortality, the preoperative nomogram, postoperative nomogram, and stage, size, grade and necrosis score showed concordance indices of 0.866, 0.897, and 0.828, respectively (P\\u2009=\\u20090.123 and 0.008 compared with stage, size, grade and necrosis score for preoperative or postoperative nomograms).",
            "output": [
                "Do nomograms incorporating serum C-reactive protein effectively predict mortality before and after surgical treatment of renal cell carcinoma?"
            ]
        },
        {
            "id": "task847-921074a0930c4233918c4ab261832537",
            "input": "Hypercholesterolemia is a well-established risk factor for the development of kidney injury. Considering that female sex hormones may play a preventative role in both cardiovascular and renal diseases, the aim of the present study was to evaluate the effects of female sex hormones on hypercholesterolemia-induced renal dysfunction.', \"Apolipoprotein E-deficient (ApoE) and C57 control female mice underwent an ovariectomy (OVX) or sham surgery and after 2 months, creatinine clearance, uremia and proteinuria were determined. Renal oxidative stress and lipid deposition were also quantified. Values are presented as mean\\u2009\u00b1\\u2009SEM. Statistical analyses were performed using Two-way ANOVA followed by Tukey's post hoc test.\", 'Creatinine clearance (\u03bcL/min) was similar between C57 (171\\u2009\u00b1\\u200917) and ApoE (140\\u2009\u00b1\\u200926) mice underwent sham surgery. OVX resulted in a reduced glomerular filtration rate in both C57 (112\\u2009\u00b1\\u20098, ~\\u2009-\\u200935%, p\\u2009<\\u20090.05) and ApoE (61\\u2009\u00b1\\u200910, ~\\u2009-\\u200956%, p\\u2009<\\u20090.05) animals. Plasma levels of urea (mg/dL) were higher in both ApoE groups (Sham: 73\\u2009\u00b1\\u20097; OVX: 73\\u2009\u00b1\\u20098, p\\u2009<\\u20090.05) when compared to C57 animals (Sham: 49\\u2009\u00b1\\u20093; OVX: 60\\u2009\u00b1\\u20094), with no changes among ovariectomized groups. Proteinuria levels (mg/24 h) were similar between C57 (Sham: 25.1\\u2009\u00b1\\u20095.7; OVX: 33.7\\u2009\u00b1\\u20094.7) and ApoE sham animals (26.4\\u2009\u00b1\\u20093.5), however, 24-h urine protein excretion was augmented in ApoE OVX animals (49.6\\u2009\u00b1\\u20095.8, p\\u2009<\\u20090.05). Histological kidney analysis demonstrated that the absence of female sex hormones resulted in increased oxidative stress, which was more severe in ApoE mice (C57 Sham: 9.2\\u2009\u00b1\\u20090.4; C57 OVX: 22.9\\u2009\u00b1\\u20091.0; ApoE Sham: 13.9\\u2009\u00b1\\u20090.7; ApoE OVX: 34.0\\u2009\u00b1\\u20091.4 au x 103, p\\u2009<\\u20090.05). As expected, ApoE mice presented higher lipid deposition, which was not affected by OVX (C57 Sham: 0\\u2009\u00b1\\u20090; C57 OVX: 0\\u2009\u00b1\\u20090; ApoE Sham: 6.8\\u2009\u00b1\\u20091.6; ApoE OVX: 5.2\\u2009\u00b1\\u20090.8% x 10-2, p\\u2009<\\u20090.05). Ovariectomy resulted in a similar reduction in ER-\u03b1 protein expression in the renal cortex (C57: 0.78\\u2009\u00b1\\u20090.04; ApoE: 0.81\\u2009\u00b1\\u20090.04 au, p\\u2009<\\u20090.05) when compared to sham animals (C57:1.00\\u2009\u00b1\\u20090.04; ApoE: 1.03\\u2009\u00b1\\u20090.03 au).",
            "output": [
                "Do endogenous female sex hormones delay the development of renal dysfunction in apolipoprotein E-deficient mice?"
            ]
        },
        {
            "id": "task847-1cbec27f55e344ed9e9e6424d780cae1",
            "input": "Electrogram fractionation and atrial fibrosis are both thought to be pathophysiological hallmarks of evolving persistence of atrial fibrillation (AF), but recent studies in humans have shown that they do not colocalize. The interrelationship and relative roles of fractionation and fibrotic change in AF persistence therefore remain unclear.', 'The aim of the study was to examine the hypothesis that electrogram fractionation with increasing persistence of AF results from localized conduction slowing or block due to changes in atrial connexin distribution in the absence of fibrotic change.', 'Of 12 goats, atrial burst pacemakers maintained AF in 9 goats for up to 3 consecutive 4-week periods. After each 4-week period, 3 goats underwent epicardial mapping studies of the right atrium and examination of the atrial myocardium for immunodetection of connexins 43 and 40 (Cx43 and Cx40) and quantification of connective tissue.', 'Despite refractoriness returning to normal in between each 4-week period of AF, there was a cumulative increase in the prevalence of fractionated atrial electrograms during both atrial pacing (control and 1, 2, and 3 months period of AF 0.3%, 1.3% \u00b1 1.5%, 10.6% \u00b1 2%, and 17% \u00b1 5%, respectively; analysis of variance, P < .05) and AF (0.3% \u00b1 0.1%, 2.3% \u00b1 1.2%, 14% \u00b1 2%, and 23% \u00b1 3%; P < .05) caused by colocalized areas of conduction block during both pacing (local conduction velocity <10 cm/s: 0.1% \u00b1 0.1%, 0.3% \u00b1 0.6%, 6.5% \u00b1 3%, and 6.9% \u00b1 4%; P < .05) and AF (1.5% \u00b1 0.5%, 2.7% \u00b1 1.1%, 10.1% \u00b1 1.2%, and 13.6% \u00b1 0.4%; P < .05), associated with an increase in the heterogeneity of Cx40 and lateralization of Cx43 (lateralization scores: 1.75 \u00b1 0.89, 1.44 \u00b1 0.31, 2.85 \u00b1 0.96, and 2.94 \u00b1 0.31; P < .02), but not associated with change in connective tissue content or net conduction velocity.",
            "output": [
                "Is fractionation of electrograms caused by colocalized conduction block and connexin disorganization in the absence of fibrosis as AF becomes persistent in the goat model?"
            ]
        },
        {
            "id": "task847-f8d81c5926d14908acfa06bc09be96ed",
            "input": "Weight loss and malnutrition are poorly tolerated by geriatric patients, and pancreaticoduodenectomy (PD) can result in chronic malabsorption and weight loss. We sought to determine how preoperative severe nutritional risk (SNR), as defined by the American College of Surgeons National Surgical Quality Improvement Program/American Geriatric Society Best Practice Guidelines, affects long-term survival after PD for benign disease among geriatric and nongeriatric patients.', 'All patients undergoing PD for nonmalignant conditions at a single center between 1995 and 2013 were followed for survival, excluding patients who died within 90 days of surgery. Survival of geriatric (age \u226565 years) and nongeriatric (age <65 years) patients with and without SNR was compared using Kaplan Meier methods. Cox regression was performed.', 'There were 320 patients who underwent PD for benign disease. Over the course of the study, the proportion of geriatric patients undergoing PD for benign conditions increased from 25% to 46%. In addition to being older, geriatric patients undergoing PD for benign disease were significantly more likely to have coronary artery disease (CAD) and hypertension. Geriatric patients with preoperative SNR had significantly decreased long-term survival after PD for benign disease (p < 0.001), with roughly 1 in 3 patients dead at 5 years compared with 1 in 14 patients without SNR. Survival was not significantly different among nongeriatric patients with and without SNR. In geriatric patients, age, CAD, and SNR were significantly associated with decreased survival on both univariate and multivariate analysis.",
            "output": [
                "Does severe nutritional risk predict decreased long-term survival in geriatric patients undergoing pancreaticoduodenectomy for benign disease?"
            ]
        },
        {
            "id": "task847-516fee4ab35c49dbbf90019fe2d24dbd",
            "input": "Peripherally administered oxytocin (OT) has produced antipsychotic drug (APD)-like effects in animal tests that are predictive of APD efficacy. However, these effects have mainly been demonstrated using animal models of schizophrenia-like deficits in prepulse inhibition (PPI) of the startle reflex. Another schizophrenia-relevant abnormality that is the basis of a predictive animal test for APD efficacy is deficient latent inhibition (LI). LI is the normal suppression of a classically conditioned response when the subject is pre-exposed to the conditioned stimulus (CS) before it is paired with the unconditioned stimulus (UCS). Conditioned taste aversion (CTA), the normal avoidance of ingesting a food or liquid by animals when its taste is associated with an aversive experience, was used to test whether OT facilitates LI consistent with APDs.', 'Brown Norway rats, known to naturally display attenuated LI, were aversively conditioned on two consecutive exposures to flavored drinking water (0.1% saccharin) by pairing it with malaise-inducing lithium chloride injections. Concurrent with conditioning, rats received subcutaneous OT (0.02, 0.1, 0.5mg/kg) or saline. Some rats were pre-exposed to the flavored water prior to its aversive conditioning (pre-exposed) while others were not (non pre-exposed). Two days after aversive conditioning the amount of flavored water consumed during a 20-min session was recorded.', 'As expected, LI, defined as greater consumption by pre-exposed vs. non pre-exposed rats was only weakly exhibited in Brown Norway rats and OT enhanced LI by reducing CTA in pre-exposed rats in a dose-dependent manner, with the 0.02 mg/kg dose producing the strongest effect.",
            "output": [
                "Does peripherally administered oxytocin modulate latent inhibition in a manner consistent with antipsychotic drugs?"
            ]
        },
        {
            "id": "task847-c667e23072e3407fbd2b7d951b45a038",
            "input": "In the United States, patients who enroll in chemotherapy trials seldom reflect the attributes of the general population with cancer, as they are often younger, more functional, and have less comorbidity. We compared survival following three chemotherapy regimens according to the setting in which care was delivered (ie, clinical trial vs usual care) to determine the generalizability of clinical trial results to unselected elderly Medicare patients.', 'Using SEER-Medicare data, we estimated survival for elderly patients (ie, age 65 years or older, n = 14097) with advanced pancreatic or lung cancer following receipt of one of three guideline-recommended first-line chemotherapy regimens. We compared their survival to that of similarly treated clinical trial enrollees, without age restrictions, with the same diagnosis and stage (n = 937). All statistical tests were two-sided.', 'Trial patients were 9.5 years younger than elderly Medicare patients. Medicare patients were more often white and tended to live in areas of greater educational attainment than trial enrollees. For each tumor type, Medicare patients who were 75 years or older had median survivals that were six to eight weeks shorter than those of trial patients (4.3 vs 5.8 months following treatment with single agent gemcitabine for advanced pancreatic cancer, P = .03; 7.3 vs 8.9 months following treatment with carboplatin and paclitaxel for stage IV non-small cell lung cancer, P = .91; 8.2 vs 10.2 months following treatment with CDDP/ VP16 for extensive stage small cell lung cancer, P \u2264 .01), whereas younger Medicare patients had survival times that were similar to those of trial patients.",
            "output": [
                "Does generalizability of trial result to elderly Medicare patients with advanced solid tumors ( Alliance 70802 )?"
            ]
        },
        {
            "id": "task847-538288670c17479f8ce05a028b336933",
            "input": "Diets high in cruciferous vegetables are associated with lower risk of incidence of prostate cancer, including aggressive forms of this disease. Human intervention studies with cruciferous vegetable-rich diets also demonstrate modulation of gene expression in important pathways in prostate cells.', 'Sulforaphane is a constituent of these foods postulated to harbor the anti-neoplastic activity based on multiple tumor models. Our own work demonstrates that sulforaphane inhibits AR signaling in prostate cancer cells. Here, we report results from the first clinical trial of sulforaphane-rich extracts in men with prostate cancer.', 'We treated 20 patients who had recurrent prostate cancer with 200 \u03bcmoles/day of sulforaphane-rich extracts for a maximum period of 20 weeks and determined the proportion of patients with \u226550% PSA declines, the primary endpoint. Only one subject experienced a \u226550% PSA decline. Thus, the primary endpoint was not achieved. Seven patients experienced smaller PSA declines (<50%). There was also a significant lengthening of the on-treatment PSA doubling time (PSADT) compared with the pre-treatment PSADT [6.1 months pre-treatment vs. 9.6 months on-treatment (p\\u2009=\\u20090.044)]. Finally, treatment with sulforaphane-rich extracts was safe with no Grade 3 adverse events.",
            "output": [
                "Do a phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer?"
            ]
        },
        {
            "id": "task847-adaf0f46d1d545e69521bcfb770d752a",
            "input": "It has been reported that beta-blockers (BB) reduce cardiovascular events in patients with atherosclerotic disease. However, little is known about the efficacy of these drugs in patients with critical limb ischemia (CLI). We investigated whether beta-blocker therapy affects the clinical outcomes of CLI patients.', 'Between March 2004 and December 2011, 1,873 consecutive CLI patients who received endovascular therapy (EVT) (394 BB-treated patients and 1,479 non-BB-treated patients) for de novo infrainguinal lesions were identified retrospectively. A propensity score analysis was used for risk adjustment in a multivariable analysis and one-to-one matching (BB: 305, non-BB 305). The primary endpoint was amputation-free survival (AFS), and the secondary endpoints were overall survival and the rates of limb salvage and freedom from major adverse limb events (MALE; including repeat reintervention, surgical conversion and major amputation). The mean follow-up period was 22 \u00b1 15 months.', 'In the propensity score-matched pair analysis, there were no significant differences in AFS between the patients treated with and without beta-blockers (58.8% vs. 58.5% at three years, log-rank p = 0.76). There were also no significant differences in the limb salvage rate (88.3% vs. 88.8 at three years, log-rank P = 0.41), overall survival (63.0% vs. 62.4% at three years, log-rank P = 0.70) and freedom from MALE (43.6% vs. 44.9% at three years, log-rank P = 0.58) between the patients treated with and without beta-blockers.",
            "output": [
                "Does beta-blocker Treatment Worsen Critical Limb Ischemia in Patients Receiving Endovascular Therapy?"
            ]
        },
        {
            "id": "task847-cef6dd13d7ad4effbe0b40b2c09af243",
            "input": "Capacitive-resistive electric transfer (CRET) is a non invasive electrothermal therapy that applies electric currents within the 400 kHz - 450 kHz frequency range to the treatment of musculoskeletal lesions. Evidence exists that electric currents and electric or magnetic fields can influence proliferative and/or differentiating processes involved in tissue regeneration. This work investigates proliferative responses potentially underlying CRET effects on tissue repair.', 'XTT assay, flow cytometry, immunofluorescence and Western Blot analyses were conducted to asses viability, proliferation and differentiation of adipose-derived stem cells (ADSC) from healthy donors, after short, repeated (5 m On/4 h Off) in vitro stimulation with a 448-kHz electric signal currently used in CRET therapy, applied at a subthermal dose of 50 \u03bcA/mm(2) RESULTS: The treatment induced PCNA and ERK1/2 upregulation, together with significant increases in the fractions of ADSC undergoing cycle phases S, G2 and M, and enhanced cell proliferation rate. This proliferative effect did not compromise the multipotential ability of ADSC for subsequent adipogenic, chondrogenic or osteogenic differentiation.",
            "output": [
                "Does electric stimulation at 448 kHz promote proliferation of human mesenchymal stem cells?"
            ]
        },
        {
            "id": "task847-02594fe76c2c4205a4ca317ccb51199a",
            "input": "Recent research suggests that preintervention functional magnetic resonance imaging (fMRI) data may predict weight loss outcomes among patients who participate in a behavioral weight loss plan. No study has examined whether presurgical brain activation can predict outcomes following bariatric surgery.', 'The aim of the present study was to determine if brain activations during a presurgical fMRI food-motivation paradigm are associated with weight loss 3 and 6 months following laparoscopic adjustable gastric banding (LAGB). Nineteen participants viewed food and nonfood pictures from a well-established food motivation paradigm during an fMRI scanning session before LAGB surgery. Weight was assessed presurgery and 3 and 6 months postsurgery; data for all participants was available at each time point. fMRI data were analyzed using the BrainVoyager QX statistical package. Whole brain voxelwise correlations of presurgery (food-nonfood) brain activation and weight, corrected for multiple comparisons, were performed to analyze the relationship between presurgical brain activation and subsequent weight loss. The settings were a medical university brain imaging center and 2 surgical weight loss centers in a major metropolitan area.', 'Increased activity in frontal regions associated with cognitive control (medial, middle, superior frontal gyrus) and posterior cingulate cortex was associated with weight loss following LAGB.",
            "output": [
                "Is pre-surgical cortical activation to food pictures associated with weight loss following bariatric surgery?"
            ]
        },
        {
            "id": "task847-8ce9f4742bee4f58b1cc2acc66b6bbf9",
            "input": "There is a robust comorbidity between mood disorders and cardiovascular disorder (CVD). The atherogenic index of plasma (AIP) and the atherogenic coefficient (AC) are important atherogenic indexes. The aims of this study were to delineate whether AIP and AC are increased in mood disorders especially when comorbid with tobacco use disorder (TUD).', 'In this case-control study we included 134 patients with mood disorders, bipolar disorder and unipolar depression (cases), and 197 individuals without mood disorder (controls) divided into those with and without TUD (defined as never-smokers). Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were measured. AIP and AC were computed as log (TG/HDLc) and non-HDLc/HDLc, respectively.', 'The AIP and AC indexes were significantly increased in patients with mood disorders versus controls, both in depression and bipolar disorder. Patients with mood disorder without TUD and patients with TUD without mood disorder showed higher AIP and AC values than never-smokers while those with comorbid mood disorders and TUD showed significantly higher AIP and AC levels than all other individuals. A large part of the variance in the AIC (26.4%) and AC (20.4%) was explained by mood disorders, TUD, male gender and body mass index.",
            "output": [
                "Are atherogenic index of plasma and atherogenic coefficient increased in major depression and bipolar disorder , especially when comorbid with tobacco use disorder?"
            ]
        },
        {
            "id": "task847-f625d260a38c48bd953dd7d6b4fca6d6",
            "input": "We evaluated the prognostic value of mid-regional proadrenomedullin (MR-proADM) in atrial fibrillation (AF) patients undergoing radiofrequency ablation.', 'Plasma concentrations of MR-proADM were measured at baseline and after 12months in 87 AF patients in whom radiofrequency ablation was performed. The association between MR-proADM and AF recurrence was tested by univariable and multivariable Cox models.', 'In all 87 patients radiofrequency ablation was successfully performed. Of the total population 54% had paroxysmal AF. The mean left ventricular ejection fraction was 54% (minimum 25%). After 12months of follow-up, 71% of the patients were free of AF recurrence. At baseline, mean MR-proADM in the total population was 0.72nmol/l\u00b10.22. Patients with AF recurrence had significantly higher baseline MR-proADM (0.89nmol/l\u00b10.29) as compared with patients without AF recurrence (0.65nmol/l\u00b10.14; p<0.001). After 12months, mean MR-proADM plasma concentration remained higher in patients with AF recurrence (0.81nmol/l\u00b10.22 as compared with patients free of AF 0.54nmol/l\u00b10.20; p<0.001). Receiver operating characteristic (ROC) curve analysis for MR-proADM yields a specificity of 98% and a sensitivity of 64% with an optimal cut-off value of 0.82nmol/l to predict recurrence of AF after catheter ablation. In the logistic regression analysis only MR-proADM remained independently predictive for AF recurrence.",
            "output": [
                "Do mid-regional proadrenomedullin levels predict recurrence of atrial fibrillation after catheter ablation?"
            ]
        },
        {
            "id": "task847-8b5ca7cb518b4c9a9d33574ccf4b9dd7",
            "input": "Pulmonary artery hypertension (PAH) is characterized by vascular remodeling, high pulmonary blood pressure, and right ventricular hypertrophy. Oxidative stress, inflammation and pulmonary artery remodeling are important components in PAH. Ellagic acid (EA) is a phenolic compound with anti-oxidative, anti-inflammatory, and anti-proliferative properties. This study aimed to investigate whether EA could prevent the development of monocrotaline (MCT)-induced PAH in rats.', 'Male Sprague-Dawley rats received EA (30 and 50mg/kg/day) or vehicle one day after a single-dose of monocrotaline (MCT, 60mg/kg). Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were assessed 4weeks later. Activation of the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome pathway in the lungs was assessed using Western blot analysis.', 'MCT induced PAH, oxidative stress, and NLRP3 inflammasome activation in vehicle-treated rats. EA reduced the right ventricle systolic pressure, the right ventricular hypertrophy and the wall thickness/external diameter ratio of the pulmonary arteries compared with vehicle. EA also inhibited the MCT-induced elevation of oxidative stress, NLRP3, and caspase-1, IL-\u03b2 in the lungs and the elevated levels of brain natriuretic peptide (BNP) and inflammatory cytokines in serum.",
            "output": [
                "Does ellagic acid prevent monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats?"
            ]
        },
        {
            "id": "task847-e9955fb77e854ff1a02a7db13e8bf929",
            "input": "Recent studies show that vascular endothelial growth factor (VEGF) downregulation is implicated in preeclampsia (PE) pathophysiology. This study assessed the relationship between PE and VEGF levels produced by peripheral blood mononuclear cells (PBMCs) and their serum levels.', 'A cross-sectional design was performed in 36 patients who had hypertensive disorders during pregnancy. We also used a longitudinal design with 12 pregnant women with risk factors for PE development and/or abnormal uterine arteries by Doppler study. VEGF and soluble fms-like tyrosine kinase-1 (sFlt-1) levels were measured for all patients in both designs.', \"sFlt-1 serum was higher in preeclamptic patients (n = 26), whereas VEGF produced by stimulated PBMCs was lower than in healthy pregnant women and VEGF levels produced by stimulated PBMCs were even lower (p <0.003) in severe PE (n = 16). The receiver-operating characteristic curve analysis allowed establishing a cut-off value to identify patients with PE. VEGF production by PBMCs was 339.87 pg/mL. In addition, a robust linear regression model was performed to adjust the variance in VEGF levels. The patients' age decreased VEGF levels and was adjusted by weeks of gestation (WG) in our model. In the longitudinal study, 7/12 patients developed PE. VEGF produced by PBMCs cells was significantly lower in PE at 24-26 WG.",
            "output": [
                "Is preeclampsia associated with lower production of vascular endothelial growth factor by peripheral blood mononuclear cells?"
            ]
        },
        {
            "id": "task847-5073e5648af949af899b1232488d3229",
            "input": "Freezing of gait (FOG) is a major concern for Parkinson's disease (PD) patients because it is a leading cause of falls and is associated with poor quality of life. The pathophysiology is unknown but it is hypothesized that it relates to cognitive abnormalities; particularly executive and visuospatial dysfunction. However, prior results have been discrepant. Pharmacologic subtypes of FOG include those that are responsive and unresponsive to levodopa.\", 'To determine whether executive and visuospatial dysfunction are associated specifically with the levodopa unresponsive subtype of FOG.', '135 PD subjects completed a single assessment included FOG questionnaire, UPDRS motor scale, comprehensive cognitive battery and measure of hallucinations. Analyses compared unresponsive (n\\xa0=\\xa016), responsive (n\\xa0=\\xa020) and no FOG (n\\xa0=\\xa099) subtypes.', 'The unresponsive subtype had a significantly older age of onset of PD than the responsive group (p\\xa0=\\xa0.03) and had worse motor scores (p\\xa0=\\xa0.003) than the no FOG group. Longer disease duration was associated with the responsive group compared to the no FOG group (p\\xa0=\\xa0.002). The unresponsive FOG group had significantly poorer visuospatial ability (p\\xa0=\\xa0.001) and executive functioning (p\\xa0=\\xa0.02) than both the no and responsive FOG subgroups. These latter groups were not significantly different. The responsive FOG group was associated with the presence of hallucinations.",
            "output": [
                "Do freezing of gait subtypes have different cognitive correlates in Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-1f60af77f0b84019ae65cc576cd6f3dc",
            "input": "During cardiopulmonary resuscitation (CPR), myocardial blood flow generated by chest compression rarely exceeds 35% of its normal level. Cardiac output generated by chest compression decreases gradually with the prolongation of cardiac arrest and resuscitation. Early studies have demonstrated that myocardial blood flow during CPR is largely dependent on peripheral vascular resistance. In this study, we investigated the effects of chest compression in combination with physical control of peripheral vascular resistance assisted by tourniquets on myocardial blood flow during CPR.', 'Ventricular fibrillation was induced and untreated for 7 min in ten male domestic pigs weighing between 33 and 37 kg. The animals were then randomized to receive CPR alone or a tourniquet assisted CPR (T-CPR). In the CPR alone group, chest compression was performed by a miniaturized mechanical chest compressor. In the T-CPR group, coincident with the start of resuscitation, the thin elastic tourniquets were wrapped around the four limbs from the distal end to the proximal part. After 2 min of CPR, epinephrine (20 \u03bcg/kg) was administered via the femoral vein. After 5 min of CPR, defibrillation was attempted by a single 150 J shock. If resuscitation was not successful, CPR was resumed for 2 min before the next defibrillation. The protocol was continued until successful resuscitation or for a total of 15 min. Five minutes after resuscitation, the elastic tourniquets were removed. The resuscitated animals were observed for 2h.', 'T-CPR generated significantly greater coronary perfusion pressure, end-tidal carbon dioxide and carotid blood flow. There was no difference in both intrathoracic positive and negative pressures between the two groups. All animals were successfully resuscitated with a single shock in both groups. There were no significant changes in hemodynamics observed in the animals treated in the T-CPR group before-and-after the release of tourniquets at post-resuscitation 5 min.",
            "output": [
                "Does a tourniquet assisted cardiopulmonary resuscitation augment myocardial perfusion in a porcine model of cardiac arrest?"
            ]
        },
        {
            "id": "task847-6a0221fff46b4660bf8bdc5a44b402c6",
            "input": "Hirschsprung disease (HSCR) is a rare multigenic congenital disorder characterized by the absence of the enteric ganglia. To date, single nucleotide polymorphisms (SNPs) in pre-miRNAs have been confirmed related with some diseases. Thus, we hypothesized that pre-miRNA polymorphisms might contribute to HSCR susceptibility. We investigated whether rs2910164 and rs11614913 of pre-miR-146a and pre-miR-196a2, are associated with HSCR.', 'Polymorphisms were genotyped using the Taqman method. Real-time PCR was used for detecting the expression level of miR-146a and its target gene ROBO1 in CC and GG genotypes.', 'Significant differences were found in the genotype distribution of rs2910164 and rs11614913 polymorphism between HSCR cases and controls (p = 0.023 and 0.041, respectively). Furthermore, G allele of rs2910164 might increase the risk of HSCR (OR, 1.54; 95% CI, 1.06-2.23). Moreover, the expression level of miR-146a for homozygote GG was also higher than homozygote CC (p = 0.0193). In contrast, the expression level of its target gene ROBO1 predicted in bioinformatics for homozygote GG was much lower than homozygote CC (p = 0.0096).",
            "output": [
                "Does a common polymorphism in pre-miR-146a underlie Hirschsprung disease risk in Han Chinese?"
            ]
        },
        {
            "id": "task847-8c5a6778606346e3b0681097cee21cb5",
            "input": "The effect of litter size and suckling intensity on the expression of KiSS-1 mRNA in the arcuate nucleus (ARC) of rats were evaluated.', 'Thirty two pregnant and four non-lactating ovariectomized (as control group) rats were used in this experiment. Lactating rats were allotted to eight equal groups. In three groups, litter size was adjusted to 5, 10, or 15 pups upon parturition and allowed to suckle their pups continuously by 8 days postpartum. In the other three groups, litter size was adjusted to five upon birth; the pups were separated from the dams for 6 hr on day 8 postpartum, after which the pups were allowed to suckle their dams for 2.5, 5, or 7.5 min prior to killing the dams. Two groups of lactating rats with either 10 or 15 pups were separated from their pups for 6 hr on day 8 postpartum, after which the pups were allowed to suckle their dams for 5 min before the dams were killed on day 8 postpartum. The ARC was removed and the expression of KiSS-1 mRNA was evaluated, using real-time PCR.', 'The expression of KiSS-1 mRNA in the ARC was decreased as the litter size and intensity of suckling stimulus were increased. The effect of suckling intensity on the expression of KiSS-1 mRNA was more pronounced than that of litter size.",
            "output": [
                "Do increased litter size and suckling intensity inhibit KiSS-1 mRNA expression in rat arcuate nucleus?"
            ]
        },
        {
            "id": "task847-3386038fed6444f297c641e3837bcabc",
            "input": "To examine the impact of glaucoma and visual acuity (VA) and visual field (VF) losses on psychosocial functioning (PF).', 'Cross-sectional study.', 'We compared PF between 192 participants with bilateral glaucoma with VA or VF losses and 40 controls from a tertiary eye hospital clinic in Singapore.', 'Glaucoma was defined using the Hodapp-Anderson-Parish criteria. Four psychosocial outcomes of the Glaucoma Quality of Life 36 questionnaire were psychometrically assessed using Rasch analysis. Multivariate regression was performed to determine the independent impact of glaucoma and VA and VF losses on PF. The impact of VA and VF on PF were evaluated by restricted cubic spline analysis.', 'Anxiety, self-image, psychological well-being, and confidence in health care.', 'The mean age of participants was 66.2\u00b111.0 years, and 63% were male. In the better eye, VA and mean deviation were Snellen 20/25 and -8.89\u00b16.52 dB, respectively. In multivariate models, glaucoma patients had 63.0% greater anxiety (95% confidence interval [CI], -66.0% to -61.2%; P<0.001), 71.0% lower self-image (95% CI, -74.1% to -68.5%; P<0.001), 38.3% less psychological well-being (95% CI, -37.4% to -39.0%; P<0.001), and 32.4% reduced confidence in health care than patients without glaucoma. The worst VA and VF categories had the most reduced PF (range, 26.0% to 81.5%; P<0.001 for all associations) compared with controls. With worsening VA, there was a linear increase in anxiety (P=0.009) and decrease in self-image (P=0.005). With worsening VF from 0 to -12.1 dB (P=0.003), anxiety increased before plateauing. Self-image decreased as VF worsened from 0 to -10 dB (P<0.001), and confidence in health care decreased when VF worsened from 0 to -9.3 dB (P=0.008). However, self-image and confidence in health care actually improved at greater levels of VF loss beyond these thresholds.",
            "output": [
                "Do glaucoma and associated visual acuity and field loss significantly affect glaucoma-specific psychosocial functioning?"
            ]
        },
        {
            "id": "task847-7326de87413247b187ec0e7c76f64a54",
            "input": "Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA) inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard.', 'Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R) blocking administered in CSF.', 'We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867) and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity.",
            "output": [
                "Does unilateral Hypothalamus Inactivation prevent PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation?"
            ]
        },
        {
            "id": "task847-52cfaab048334ec08c8b83ea191ddad1",
            "input": "Formalin injection induces nociceptive bahaviour in phase I and II, with a quiescent phase between them. While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet. Phase II is a consequence of peripheral and central sensitization processes, which can lead to termination of the noxious stimuli responses; 45-60 minutes after formalin injection via possible recruitment of active inhibitory mechanisms which we have investigated in this study.', 'To test our hypothesis, in the first set of experiments, we evaluated nociceptive response after two consecutive injection of formalin (50\u00b5L, 2%), with intervals of 5 or 60 minutes. In the next set, formalin tests were carried out in companion with injection of Naloxone Hydrochloride, a non-selective antagonist of opioid receptors, pre-formalin injection and 30 and 45 minutes post formalin injection.', 'While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection. While second injection of formalin, 5 minute after first injection, had no effect. Administration of naloxone (1mg/kg) decreased nociception in phase 2A; but had no effect on delayed termination of formalin test.",
            "output": [
                "Is termination of Nociceptive Bahaviour at the End of Phase 2 of Formalin Test Attributable to Endogenous Inhibitory Mechanisms , but not by Opioid Receptors Activation?"
            ]
        },
        {
            "id": "task847-80f3af572df94231a32d00a2d9a9e906",
            "input": "To improve the extent over which whole brain quantitative three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers.', 'Two short echo time (20 ms) acquisitions of 3D echo planar spectroscopic imaging at two orientations, one in the anterior commissure-posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15\u00b0 plane were obtained at 3 Tesla in a group of 10 healthy volunteers. B1 (+) , B1 (-) , and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained.', 'The combined metabolite maps derived from the two acquisitions reduced the regional intersubject variance. The numbers of AAL regions showing N-acetyl aspartate (NAA) SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15\u00b0 orientation, to a value of 76 regions of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA = 10.03 + 1.71; cCho = 1.78 \u00b1 0.55; cCr = 7.29 \u00b1 1.69; cmIns = 5.30 \u00b1 2.67) and in cerebellum (cNAA = 5.28 \u00b1 1.77; cCho = 1.60 \u00b1 0.41; cCr = 6.95 \u00b1 2.15; cmIns = 3.60 \u00b1 0.74).",
            "output": [
                "Do whole-brain quantitative mapping of metabolites using short echo three-dimensional proton MRSI?"
            ]
        },
        {
            "id": "task847-e7176b8f559e4d9189c95ad4c6bb7a34",
            "input": "The aim of this study was to investigate the relationship between intraoperative vasopressin infusion and postoperative cardiac enzymes.', 'A prospective, double-blind, randomized, controlled study.', 'A single tertiary cardiac center.', 'One hundred consecutive patients undergoing cardiac surgery with or without cardiopulmonary bypass.', 'The study was approved by the Institutional Review Board, and patients provided informed consent to participate. Patients were randomized by computer into 2 equal groups: Vasopressin or control. The blinded study included vasopressin administered at a dose of 1.8 U/h or 1.8 mL/h of normal saline, along with catecholamines. The drug was administered continually during surgery while patients needed catecholamines. The intervention was discontinued upon admission to the intensive care unit when information regarding the true character of the drug was reported to the doctor in charge of patients in the intensive care unit by one of the investigators. Primary outcomes were CK-MB and troponin T levels measured at 0, 6, and 12 hours postoperatively.', 'Of the 100 patients, 8 were excluded; the remaining 92 were randomized to either the vasopressin (n = 47) or control (n = 45) group. There were no significant differences in demographic data between the groups. Postoperatively at 0, 6, and 12 hours, there were no differences in CK-MB (U/l) (37.5 \u00b1 57.9 v 32.0 \u00b1 21.5, 29.4 \u00b1 41.1 v 24.4 \u00b1 23.1, and 21.4 \u00b1 21.3 v. 21.8 \u00b1 32.4, respectively) and troponin T (752.4 \u00b1 638.2 v 762.7 \u00b1 557.1, 753.8 \u00b1 507.3 v 777.6 \u00b1 515.0, and 774.6 \u00b1 572.6 v 698.7 \u00b1 540.2, respectively) values.",
            "output": [
                "Does vasopressin raise cardiac enzymes following cardiac surgery : a randomized double-blind clinical trial?"
            ]
        },
        {
            "id": "task847-fab58e082a9748b3a18e75d8406b9284",
            "input": "Previous findings are inconsistent; yet, converging evidence suggests an association between schizophrenia (SZ) and the impairment of posttranscriptional regulation of brain development through microRNA (miRNA) systems.', 'This study aims to (1) compare the overall frequency of 121 rare variants (RVs) in 59 genes associated with the miRNA system in genome-wide association studies (GWAS)-derived data including 768 SZ cases and 1348 healthy controls and validated in an independent GWAS data including 1802 SZ cases and 1447 controls; (2) profile genome-wide miRNA expression in blood collected from 15 early-onset SZ (EOS) cases and 15 healthy controls; and (3) construct a miRNA-messenger RNA (mRNA) regulatory network using our previous genome-wide mRNA expression data generated from a separate sample of 18 EOS cases and 12 healthy controls.', 'Our findings indicate that: (1) In genes associated with the control of miRNAs, there are approximately 50% more RVs in SZ cases than in controls (P \u2264 2.62E-10); (2) The observed lower miRNA activity in EOS patients compared with the healthy controls suggests that miRNAs are abnormally downregulated; (3) There exists a predicted regulatory network among some downregulated miRNAs and some upregulated mRNAs.",
            "output": [
                "Does converging evidence implicate the abnormal microRNA system in schizophrenia?"
            ]
        },
        {
            "id": "task847-0fef42c0e9884974aa3ee2e37adde841",
            "input": "Temporomandibular joint (TMJ) disorders are common disease in maxillofacial surgery. The aim of this study is to regenerate fibrocartilage with a mixture of TMJ fibrochondrocytes and periodontal ligament derived mesenchymal stem cells (PD-MSCs).', 'Fibrochondrocytes and PD-MSC were cocultured (ratio 1\\u2009:\\u20091) for 3 weeks. Histology and glycosaminoglycans (GAGs) assay were performed to examine the deposition of GAG. Green florescent protein (GFP) was used to track PD-MSC. Conditioned medium of PD-MSCs was collected to study the soluble factors. Gene expression of fibrochondrocytes cultured in conditioned medium was tested by quantitative PCR (qPCR).', 'Increased proliferation of TMJ-CH was observed in coculture pellets when compared to monoculture. Enhanced GAG production in cocultures was shown by histology and GAG quantification. Tracing of GFP revealed the fact that PD-MSC disappears after coculture with TMJ-CH for 3 weeks. In addition, conditioned medium of PD-MSC was also shown to increase the proliferation and GAG deposition of TMJ-CH. Meanwhile, results of qPCR demonstrated that conditioned medium enhanced the expression levels of matrix-related genes in TMJ-CH.",
            "output": [
                "Do periodontal ligament mesenchymal stromal cells increase proliferation and glycosaminoglycans formation of temporomandibular joint derived fibrochondrocytes?"
            ]
        },
        {
            "id": "task847-c9d41d3aa5ea494f881dcba11b085434",
            "input": "Currently, there is no standardised screening for prostate cancer in Europe. Assessment of risk is opportunistically undertaken in consultation with the GP or urologist. Evaluation of the prostate gland consists of a prostate-specific antigen (PSA) serum level and a digital rectal examination (DRE) of the gland. DRE is an essential part of the assessment that can independently predict prostate cancer in the setting of a normal PSA level.', 'To evaluate the clinical usefulness of the DRE in general practice and urology clinics, and to ascertain its positive predictive value and sensitivity.', 'A retrospective analysis study of a cohort of Irish men who underwent TRUS guided biopsy of the prostate in a single Irish tertiary referral centre, despite a normal PSA level. Patients were identified from a Rapid Access Prostate Clinic patient database. Pathological biopsy results were correlated with clinical DRE findings.', 'Patient demographics, PSA levels, and DRE findings from a prospectively established database and hospital data systems from May 2009 to October 2013 were analysed.', 'Of 103 men referred over a 53-month period with a normal age-adjusted PSA level, 67% were referred on the basis of an abnormal DRE alone. Thirty-five per cent of males with a normal PSA had prostate cancer. DRE alone had a sensitivity and specificity of 81% and 40% respectively in diagnosing prostate cancer, with a positive predictive value of 42%. Seventy-six per cent of these men had high-grade disease.",
            "output": [
                "Is digital rectal examination in primary care important for early detection of prostate cancer : a retrospective cohort analysis study?"
            ]
        },
        {
            "id": "task847-916b8313651946359ff87222fd64dac6",
            "input": "Roux-en-Y gastric bypass (RYGB) surgery causes profound weight loss and improves insulin sensitivity (S(I)) in obese patients. Regular exercise can also improve S(I) in obese individuals; however, it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S(I) and other cardiometabolic factors.', 'We conducted a single-blind, prospective, randomized trial with 128 men and women who recently underwent RYGB surgery (within 1-3 months). Participants were randomized to either a 6-month semi-supervised moderate exercise protocol (EX, n = 66) or a health education control (CON; n = 62) intervention. Main outcomes measured included S(I) and glucose effectiveness (S(G)), which were determined from an intravenous glucose tolerance test and minimal modeling. Secondary outcomes measured were cardiorespiratory fitness (VO2 peak) and body composition. Data were analyzed using an intention-to-treat (ITT) and per-protocol (PP) approach to assess the efficacy of the exercise intervention (>120 min of exercise/week).', '119 (93%) participants completed the interventions, 95% for CON and 91% for EX. There was a significant decrease in body weight and fat mass for both groups (P < 0.001 for time effect). S(I) improved in both groups following the intervention (ITT: CON vs. EX; +1.64 vs. +2.24 min\u207b\u00b9/\u03bcU/ml, P = 0.18 for \u0394, P < 0.001 for time effect). A PP analysis revealed that exercise produced an additive S(I) improvement (PP: CON vs. EX; +1.57 vs. +2.69 min\u207b\u00b9/\u03bcU/ml, P = 0.019) above that of surgery. Exercise also improved S(G) (ITT: CON vs. EX; +0.0023 vs. +0.0063 min\u207b\u00b9, P = 0.009) compared with the CON group. Exercise improved cardiorespiratory fitness (VO2 peak) compared with the CON group.",
            "output": [
                "Does clinical trial demonstrate exercise following bariatric surgery improves insulin sensitivity?"
            ]
        },
        {
            "id": "task847-ad13be3ce02d418a830a5d3a25c28297",
            "input": "Non-human primates, when encountering human beings, show wariness and alertness. These behaviors differ when there is direct human gaze vs. when human averts his gaze.', 'We observed cynomolgus monkey in their home cage and studied their behaviors in response to human gaze. Four behaviors were analyzed: opening mouth, staring at observer, agitated activity, and approaching observer.', 'Three behaviors appeared to be sensitive to human gaze between when the human observer gazed at the monkey and when the human observer looked away. Individual animals also displayed subpatterns of responses to human gaze.",
            "output": [
                "Do differential behavior patterns in cynomolgus monkey Macaca fascicularis in home cage in response to human gaze?"
            ]
        },
        {
            "id": "task847-f0d77272497040a68acec168f0dfafd0",
            "input": "Increased small airway resistance and decreased lung elasticity contribute to the airflow limitation in chronic obstructive pulmonary disease (COPD). The lesion that corresponds to loss of lung elasticity is emphysema; the small airway obstruction is due to inflammatory narrowing and obliteration. Despite their convergence in altered physiology, different mechanisms contribute to these processes. The relationships between gene expression and these specific phenotypes may be more revealing than comparison with lung function.', 'We measured the ratio of alveolar surface area to lung volume (SA/V) in lung tissue from 43 smokers. Two samples from 21 subjects, in which SA/V differed by >49 cm2/mL were profiled to select genes whose expression correlated with SA/V. Significant genes were tested for replication in the 22 remaining subjects.', 'The level of expression of 181 transcripts was related to SA/V ( p < 0.05). When these genes were tested in the 22 remaining subjects as a replication, thirty of the 181 genes remained significantly associated with SA/V (P < 0.05) and the direction of association was the same in 164/181. Pathway and network analysis revealed enrichment of genes involved in protein ubiquitination, and western blotting showed altered expression of genes involved in protein ubiquitination in obstructed individuals.",
            "output": [
                "Are genes related to emphysema enriched for ubiquitination pathways?"
            ]
        },
        {
            "id": "task847-9d849794b5c64d1a8fe80965327dcf7e",
            "input": "Mass spectrometry-based proteomics experiments generate spectra that are rich in information. Often only a fraction of this information is used for peptide/protein identification, whereas a significant proportion of the peaks in a spectrum remain unexplained. In this paper we explore how a specific class of data mining techniques termed \"frequent itemset mining\" can be employed to discover patterns in the unassigned data, and how such patterns can help us interpret the origin of the unexpected/unexplained peaks.', 'First a model is proposed that describes the origin of the observed peaks in a mass spectrum. For this purpose we use the classical correlative database search algorithm. Peaks that support a positive identification of the spectrum are termed explained peaks. Next, frequent itemset mining techniques are introduced to infer which unexplained peaks are associated in a spectrum. The method is validated on two types of experimental proteomic data. First, peptide mass fingerprint data is analyzed to explain the unassigned peaks in a full scan mass spectrum. Interestingly, a large numbers of experimental spectra reveals several highly frequent unexplained masses, and pattern mining on these frequent masses demonstrates that subsets of these peaks frequently co-occur. Further evaluation shows that several of these co-occurring peaks indeed have a known common origin, and other patterns are promising hypothesis generators for further analysis. Second, the proposed methodology is validated on tandem mass spectrometral data using a public spectral library, where associations within the mass differences of unassigned peaks and peptide modifications are explored. The investigation of the found patterns illustrates that meaningful patterns can be discovered that can be explained by features of the employed technology and found modifications.",
            "output": [
                "Does unravelling associations between unassigned mass spectrometry peak with frequent itemset mining techniques?"
            ]
        },
        {
            "id": "task847-ef064d48d99b4eefaaf0d89cef2a3f47",
            "input": "The purpose of our study was to investigate the therapeutic potential of Celecoxib for epithelial ovarian cancer, especially on cellular morphological changes, proliferation invasion and epithelial-mesenchymal transition (EMT).', 'The MTT and transwell assays were performed to evaluate the effect of Celecoxib on proliferation and invasion ability of ovarian cancer cell lines, respectively. Western blot was carried out to detect the expression of epithelial phenotypes, E-cadherin and Keratin, and mesenchymal phenotypes, N-cadherin and Vimentin, as well as p-AKT, p-ERK and ZEB1. ZEB1 small-interfering RNA (siRNA) was used to downregulate the expression of ZEB1 to further inquiring into the downstream of Celecoxib-induced EMT.', 'Cellular morphological assessment revealed that both A2780 and SKOV3 cells gradually appeared in the morphology of mesenchymal cells after Celecoxib treatment. The MTT assay demonstrated that celecoxib had no effect on cell proliferation. Transwell assay showed that Celecoxib significantly increased the cell invasion ability. Western blot data proved that the expression of E-cadherin and keratin was elevated, whereas the expression of N-cadherin and Vimentin was decreased in a dose-dependent manner compared with the untreated cells, the expression of p-AKT, p-ERK and ZEB1 was also obviously elevated. However, ZEB1 siRNA reversed Celecoxib-induced E-cadherin expression and N-cadherin expression, as well as cellular invasiveness.",
            "output": [
                "Does celecoxib induce epithelial-mesenchymal transition in epithelial ovarian cancer cells via regulating ZEB1 expression?"
            ]
        },
        {
            "id": "task847-e6dc3eb6171d4e66a75a5ed80d43ce99",
            "input": "The aim of this study was to evaluate the expression of DACT1 in human placenta tissue and the relationship between DACT1 and target genes of the Wnt signaling pathway.', 'Real-time PCR and western blotting were used to detect the expression of DACT1 and the target genes of Wnt signaling pathway in human placenta tissue. And the relationship between them was analyzed using SPSS 19.', 'Real-time PCR results showed that DACT1 expression was significantly higher in 49- to 71-day placenta tissues (mean value\\xa0=\\xa00.020) than that in 39- to 48-day (the mean value\\xa0=\\xa00.009). The mRNA expressions of the Wnt signaling pathway target genes, CCND1, CCND2, FOSL1, DAB2 and JUN, were also increased expressed in human placenta tissues. Significant positive associations between DACT1 and CCND1, CCND2, FOSL1, DAB2 and JUN were observed. Western blotting analysis showed that the protein expression of DACT1, CCND1, CCND2, FOSL1, DAB2 and JUN displayed the increasing trend in 43-, 49- and 71-day placenta samples.",
            "output": [
                "Is dACT1 involved in human placenta development by promoting Wnt signaling?"
            ]
        },
        {
            "id": "task847-4b4d91ad3a1243cea736153441e8587e",
            "input": "Neuroendocrine tumors (NETs) of the ileum are sporadic tumors derived from submucosal gastrointestinal stem cells. They often show clinical symptoms only after hepatic metastasation when curative therapy is limited or impossible. In this study, we analyzed the expression of the candidate genes mammalian target of rapamycin (mTOR), alpha thalassemia/mental retardation syndrome X-linked (ATRX), and death domain-associated protein (DAXX) to investigate the specific oncogenetics and potential therapeutic options for ileal NETs.', 'In a prospective database, all patients who underwent surgical removal of a NET of the ileum between 2001 and 2011 were specified. Expression analysis was performed for mTOR, ATRX, and DAXX by immunohistochemistry of paraffin-embedded tumor samples. To evaluate the results the immunoreactive score was applied. Normal tissue and tumor tissue were analyzed for the comparison of gene expression levels using quantitative-real-time polymerase chain reaction for ATRX and mTOR genes. Results were correlated under pathologic and clinical aspects.', 'A total of 69 patients were admitted to the study. Positive cytosolic expression of the potential oncogene mTOR was immunohistochemically detected in 76.2% of the human probes. A loss of nuclear ATRX expression was detected in 13.0% of the samples. A nonexpression of the DAXX-protein in cell nuclei was not found (0%). Gene transcript levels did not show a significant alteration in ileal NETs in comparison with normal tissue.",
            "output": [
                "Do ileal neuroendocrine tumors show elevated activation of mammalian target of rapamycin complex?"
            ]
        },
        {
            "id": "task847-1591906a95dd409a9ebbd24aba27afcf",
            "input": "Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome.', 'To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice.', 'Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4\\xa0+ T cells, CD8\\xa0+ T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group.",
            "output": [
                "Does core needle biopsy of breast cancer tumors increase distant metastases in a mouse model?"
            ]
        },
        {
            "id": "task847-e69fe85dcf284951a5bf074b98a90d21",
            "input": "The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells.', 'HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo.', 'Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1+RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb+RT group.",
            "output": [
                "Is hAP1 gene expression associated with radiosensitivity in breast cancer cells?"
            ]
        },
        {
            "id": "task847-bf5572cfbdf1494180e9ed2b214b43f8",
            "input": "Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing.', 'Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20\\xa0minutes over two weeks using anodal (1\\xa0mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0-10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS.', 'Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported.",
            "output": [
                "Does patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviate pain in trigeminal neuralgia?"
            ]
        },
        {
            "id": "task847-4b10a021bfb24690ab48350248fefe15",
            "input": "Does high mobility group box protein 1 (HMGB1) regulate inflammatory reactions in a rat model of experimental autoimmune orchitis (EAO)?",
            "output": [
                "Does targeting high mobility group box protein 1 ameliorate testicular inflammation in experimental autoimmune orchitis?"
            ]
        },
        {
            "id": "task847-376589f9a78d4b9fa6fd63b561f00b9c",
            "input": "To evaluate the risk of reclassification on serial biopsy for Caucasian and African American (AA) men with very low-risk (VLR) prostate cancer enrolled in a large prospective active surveillance (AS) registry.', 'The Johns Hopkins AS registry is a prospective observational study that has enrolled 982 men since 1994. Including only men who met all National Comprehensive Cancer Network VLR criteria (clinical stage \u2264T1, Gleason score \u22646, prostate-specific antigen [PSA] level <10 ng/mL, PSA density <0.15 ng/mL/cm(3), positive cores <3, percent cancer per core \u226450), we analyzed a cohort of 654 men (615 Caucasians and 39 AAs). The association of race with reclassification on serial biopsy was assessed with competing-risks regressions.', 'AA men on AS were more likely than Caucasians to experience upgrading on serial biopsy (36% vs 16%; adjusted P <.001). Adjusting for PSA level, prostate size, volume of cancer on biopsy, treatment year, and body mass index, AA race was an independent predictor of biopsy reclassification (subdistribution hazard ratio, 1.8; P = .003). Examining specific modes of reclassification, AA race was independently associated with reclassification by grade (subdistribution hazard ratio, 3.0; P = .002) but not by volume.",
            "output": [
                "Are reclassification rates higher among African American men than Caucasians on active surveillance?"
            ]
        },
        {
            "id": "task847-1723c2c7c48a4ec7957f074cb3ee729b",
            "input": "Chemoradiotherapy for non-small cell lung cancer can impair pulmonary function, particularly when it is followed by surgery. This study aimed to document the changes in respiratory function as a result of a perioperative intensive pulmonary rehabilitation program in patients with non-small cell lung cancer who underwent induction chemoradiotherapy.', 'A total of 82 consecutive patients underwent pulmonary resection after undergoing induction chemoradiotherapy. A pulmonary rehabilitation program was started at the same time as the induction chemoradiotherapy. Standard respiratory function tests were performed before and after induction chemoradiotherapy. Treatment-related mortality and the incidence of postoperative respiratory complications were investigated. The Wilcoxon signed-rank test was used to analyze the differences in spirometric changes.', 'All patients underwent a pulmonary rehabilitation program for an average of 10 weeks. Significant increases were observed in forced vital capacity (+6.4%, P = .0096) and forced expiratory volume in 1 second (+10.4%, P < .0001). Diffusing capacity of the lung for carbon monoxide decreased (-14.0%, P < .0001). Patients with respiratory impairment (forced vital capacity <80% predicted or forced expiratory volume in 1 second/forced vital capacity <70%) showed significant improvements in forced vital capacity (+13.9%, P = .0025) and forced expiratory volume in 1 second (+22.5%, P < .0001). Significant increases were observed in forced vital capacity (+7.0%, P = .0042) and forced expiratory volume in 1 second (+10.8%, P = .0001) in patients with a smoking history. There was no mortality, and postoperative respiratory morbidity was 6.1%.",
            "output": [
                "Does pulmonary rehabilitation during induction chemoradiotherapy for lung cancer improve pulmonary function?"
            ]
        },
        {
            "id": "task847-861e505e9a364d78b351e36f838bf898",
            "input": "In this study, single nucleotide polymorphisms (SNPs) at 19 loci, previously associated with age-related macular degeneration (AMD), were systematically tested for association in patients with chronic central serous chorioretinopathy (cCSC). In addition, we evaluated the effect of detailed phenotyping on these genetic associations.', 'Case-control study.', 'We included 292 cCSC patients, 1147 AMD patients, and 1311 control individuals.', 'We genotyped SNPs at 19 AMD-associated loci and 6 additional SNPs at the complement factor H (CFH) locus. Phenotyping of all patients was based on fundoscopy, spectral-domain optical coherence tomography, fluorescein angiography (FA), and indocyanine green angiography.', 'We measured the allele frequencies of 25 AMD-associated SNPs and CFH haplotype frequencies in patients with cCSC and the effect of phenotypic subdivision of cCSC on genetic associations.', 'One SNP in ARMS2 (rs10490924) was significant after Bonferroni correction (Punadjusted=0.002; odds ratio [OR]=0.64). The SNPs at 3 other AMD loci (CFH, TNFRSF10A, ADAMTS9) showed a trend toward association with typical cCSC. Further analysis of the CFH locus identified 2 SNPs that significantly conferred increased risk for cCSC and 1 that was protective. The CFH-H3 haplotype was also found to be protective (P=0.01; OR=0.54). Using multimodal imaging, 197 patients were classified as having typical cCSC, 52 patients had unilateral abnormalities on FA that were otherwise typical of cCSC, and 43 patients had a clinical picture that could be compatible with cCSC, but with features that could also indicate other macular diseases. Significant differences of the minor allele frequencies of the tested SNPs were observed between these 3 phenotypic subgroups.",
            "output": [
                "Is chronic central serous chorioretinopathy associated with genetic variants implicated in age-related macular degeneration?"
            ]
        },
        {
            "id": "task847-d2b77143e587456089629acb23e3f008",
            "input": "To investigate the associations of IL17A, IL17F, IL23A, and IL23R copy number variants (CNVs) with Vogt-Koyanagi-Harada (VKH) syndrome and Beh\u00e7et's disease (BD) and the possible mechanisms involved.\", 'Two-stage case-control and functional studies.', 'A total of 1159 VKH patients, 1036 BD patients, and 2050 controls were enrolled.', 'TaqMan real-time polymerase chain reaction assay was used for genotyping of copy number variant. Cell proliferation was measured by colorimetric assay.', 'Association of CNVs in IL17A, IL17F, IL23A, and IL23R with BD and VKH syndrome and the functional roles of IL17F CNVs.', 'Increased frequencies of more than 2 copies of IL17F and IL23A were found in BD patients as compared with controls (IL17F: P=4.17\u00d710(-8); odds ratio [OR], 2.2; IL23A: P=2.86\u00d710(-11); OR, 2.8, respectively). A similar result was found for VKH syndrome (IL17F: P=2.84\u00d710(-13); OR, 2.7; IL23A: P=4.46\u00d710(-17); OR, 3.4, respectively). Interestingly, the association of IL17F and IL23A with BD was found only in male patients (IL17F: P=1.06\u00d710(-6); OR, 2.3; IL23A, P=3.81\u00d710(-8); OR, 2.8, respectively), but not in female patients. No association of CNVs in IL17A and IL23R was found for BD and VKH syndrome. IL17F protein levels were correlated positively with gene copy numbers (P=3.43\u00d710(-7)). Individuals with high IL17F copies showed enhanced peripheral blood mononuclear cells (PBMC) proliferation (P=5.67\u00d710(-3)).",
            "output": [
                "Do genetic variations of IL17F and IL23A show associations with Beh\u00e7et 's disease and Vogt-Koyanagi-Harada syndrome?"
            ]
        },
        {
            "id": "task847-f95e9e9eacfa47c1982a06b2d226d840",
            "input": "Upper alveolar nerves, when injured during Le Fort I osteotomies, alter maxillary tooth sensitivity. We had for aim to analyze post-operative maxillary tooth sensitivity recovery.', 'We conducted a prospective study in a series of patients having undergone Le Fort I osteotomy, with, or without mandibular osteotomy or intermaxillary disjunction (IMD). The direction and range of displacement of the maxillary bone were recorded. One tooth in each alveolar sector (incisivocanine, premolar, molar) was tested with an electric stimulator for each patient. The tests were performed before (D-1), and after surgery (D2 or day+2, D+15, M2 (or month +2), M3, and M6).', 'Twenty-two patients were included. Among the tested teeth, 91.9 % were sensitive at D-1. At D2, only 12.7 % of teeth were sensitive. At D15, M2, M3, and M6, the sensitivity was respectively 33.3 %, 43.1 %, 50 %, and 61.8 %. The recovery of sensitivity was faster in young patients (under 35 years of age) and for upper middle and superior alveolar nerves. There was no difference regarding the direction of maxillary movement.",
            "output": [
                "Do [ Recovery of maxillary tooth sensibility after Le Fort I osteotomy ]?"
            ]
        },
        {
            "id": "task847-15a7daf945ec4dfc84b7970d74c763a2",
            "input": "Although the echolucent plaque in carotid stenosis is associated with future ischemic stroke, the predictive value of echogenicity in small and medium size carotid plaques on vascular events has not been thoroughly examined. Thus, we prospectively tested the hypothesis that plaque echogenicity of carotid atheroma can predict the future total cardiovascular events in patients with vascular risk factors.', 'Ultrasound assessment of carotid intima-media complex thickness (IMT) and plaque echogenicity using integrated backscatter (IBS) analysis was performed in 596 patients aged 40 or more, with any history of vascular events or with at least 1 risk factor, who were enrolled between 2001 and 2006 in the Osaka Follow-up Study for Carotid Atherosclerosis, part 2 (OSACA2). We followed the incidence of total cardiovascular events including cerebrovascular events, coronary heart disease (CHD), and peripheral artery disease (PAD) for 6.4 years. We divided the patients into two groups according to the IBS index above (echorich plaques) and under (echolucent plaque) the median value, and calculated the hazard ratios (HR) of the echolucent group compared with the echogenic group in the risk of cardiovascular events.', 'Among 596 patients, carotid stenosis was found only in 87 patients. During the follow-up period, we observed 121 cardiovascular events including 63 cerebrovascular events, 45 CHD cases, and 13 PAD cases. The patients with incident cardiovascular events had larger plaque thickness and lower IBS index than those without incident vascular events. The relative risk of vascular events for echolucent versus echorich plaques was 1.45 (95% confidence interval [CI] 0.99-2.13, p = 0.058) after adjustment for risk factors and plaque thickness. In patients with plaque size above the median value (>2.1 mm), the relative risk of vascular events for echolucent plaques was 1.72 (95% CI 1.06-2.85, p = 0.029), but this association was not observed in patients with plaque size <2.0 mm.",
            "output": [
                "Does echogenicity of medium-to-large carotid plaques predict future vascular events?"
            ]
        },
        {
            "id": "task847-a160d769304f4df0813cab276f5beb42",
            "input": "There is a significant comorbidity between mood disorders and tobacco use disorder (TUD), which may be related to both genetic and environmental factors. Gene variants of the 5-HT transporter, such as STin2 VNTR (a variable number of tandem repeats in the functional serotonin transporter intron 2) may be associated with mood disorders and TUD.', 'This study aimed to delineate the association between the STin2 genetic polymorphism and comorbid TUD and mood disorders, including depression or bipolar disorder.', 'We examined the STin2 VNTR polymorphism in never-smokers (n=113); patients with mood disorders without TUD (n=62); patients with TUD without mood disorders (n=90); and patients with both disorders (n=95).', 'We found a significant association between the STin2 genetic polymorphism and the above diagnostic groups whereby the STin2.12 allele shows a positive association with comorbid TUD and mood disorders (Odds ratio=3.07, 95% CI=1.41-6.68), while the STin2.10/10 homozygous genotype shows a negative association (Odds ratio=0.34, 95% CI=0.16-0.74). Adjusting for years of education, age, gender, marital status and ethnicity did not change these results, but showed that TUD was associated with lower education levels and less stable relationships, whereas mood disorders were related to female gender. A family history of TUD was significantly associated with TUD in subjects without mood disorders only.",
            "output": [
                "Is sTin2 VNTR polymorphism associated with comorbid tobacco use and mood disorders?"
            ]
        },
        {
            "id": "task847-3f940ff0620e45bba85db4205ecd6e48",
            "input": "Lynch syndrome is caused by germline mutations in DNA mismatch repair genes leading to microsatellite instability (MSI) and colorectal cancer. Mesalazine, commonly used for the treatment of UC, reduces MSI in vitro. Here, we tested natural compounds for such activity and applied mesalazine and thymoquinone in a Msh2(loxP/loxP) Villin-Cre mouse model for Lynch syndrome.', 'Flow cytometry was used for quantitation of mutation rates at a CA13 microsatellite in human colon cancer (HCT116) cells that had been stably transfected with pIREShyg2-enhanced green fluorescent protein/CA13, a reporter for frameshift mutations. Mice were treated for 43\\u2005weeks with mesalazine, thymoquinone or control chow. Intestines were analysed for tumour incidence, tumour multiplicity and size. MSI testing was performed from microdissected normal intestinal or tumour tissue, compared with mouse tails and quantified by the number of mutations per marker (NMPM).', 'Besides mesalazine, thymoquinone significantly improved replication fidelity at 1.25 and 2.5\\u2005\u00b5M in HCT116 cells. In Msh2(loxP/loxP) Villin-Cre mice, tumour incidence was reduced by mesalazine from 94% to 69% (p=0.04) and to 56% (p=0.003) by thymoquinone. The mean number of tumours was reduced from 3.1 to 1.4 by mesalazine (p=0.004) and to 1.1 by thymoquinone (p<0.001). Interestingly, MSI was reduced in normal intestinal tissue from 1.5 to 1.2 NMPM (p=0.006) and to 1.1 NMPM (p=0.01) by mesalazine and thymoquinone, respectively. Thymoquinone, but not mesalazine, reduced MSI in tumours.",
            "output": [
                "Do mesalazine and thymoquinone attenuate intestinal tumour development in Msh2 ( loxP/loxP ) Villin-Cre mice?"
            ]
        },
        {
            "id": "task847-61067edfbb814753882440eee4c46f44",
            "input": "Hippocampal neurodegeneration is one of the hallmarks in neurological and neurodegenerative diseases such as temporal lobe epilepsy and Alzheimer disease. Human embryonic kidney (HEK) cells are a mixed population of cells, including neurons, and their conditioned medium is enriched with erythropoietin (EPO). Because EPO is a known neuroprotectant, we hypothesized that infusion of HEK cells or HEK-conditioned medium (HEK-CM) may provide neuroprotection against kainic acid (KA)-induced hippocampal damage in mice.', 'Adult CF1 mice were treated with KA to induce hippocampal damage. On 3rd and 5th days after KA treatment, HEK cells or HEK-CM was infused intravenously through the tail vein. On the 7th and 8th days after KA treatment, all groups of mice were subjected to cognitive and depression assessment by use of a novel object recognition test and a forced swim test, respectively. Subsequent to this assessment, mice were killed and the brain samples were used to assess the histopathology and messenger RNA expression for EPO and B-cell lymphoma-2 (Bcl-2).', 'We found that infusion of HEK cells/HEK-CM improves cognitive function and alleviates symptoms of depression. Histological assessment demonstrates complete neuroprotection against KA-mediated excitotoxicity, and the hippocampal cytoarchitecture of HEK cells/HEK-CM treated mice was comparable to normal control mice. HEK cells/HEK-CM treatment could provide neuroprotection by upregulating the endogenous EPO and Bcl-2 in KA-treated mice.",
            "output": [
                "Does infusion of human embryonic kidney cell line conditioned medium reverse kainic acid induced hippocampal damage in mice?"
            ]
        },
        {
            "id": "task847-41ab84776afe49de84fd1361a6718cce",
            "input": "The associations of transferrin saturation with diabetes have not been well evaluated and conflicting results have been reported. The purpose of this study is to examine the association of iron indices (serum ferritin and transferrin saturation) with risk of impaired fasting glucose and insulin resistance.', 'We conducted a cross-sectional study in 2413 individuals (1150 men and 1263 women) aged 20-50\\xa0years who participated in the 2010 Korean National Health and Nutrition Examination Survey. Participants were free of diabetes, malignancy, liver cirrhosis, chronic renal failure, anaemia, pregnancy and menopause. Fasting plasma glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as the outcomes.', 'Impaired fasting glucose was more prevalent in the highest compared with the lowest serum ferritin quartile among men (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.20-3.24) after adjustment for multiple covariates. Following the same adjustment, impaired fasting glucose was less prevalent in the highest compared with the lowest transferrin saturation quartile among men (OR, 0.45; 95% CI, 0.25-0.80) and women (OR, 0.33; 95% CI, 0.14-0.77). Moreover, a higher ferritin level was significantly associated with higher HOMA-IR after adjusting for confounders in men. Lower transferrin saturation was also significantly associated with higher insulin levels and HOMA-IR in both sexes.",
            "output": [
                "Is low transferrin saturation associated with impaired fasting glucose and insulin resistance in the South Korean adults : the 2010 Korean National Health and Nutrition Examination Survey?"
            ]
        },
        {
            "id": "task847-b514b1708b2146aca4d6b7a4e3c166b5",
            "input": "Maternal nutrition during different stages of pregnancy can induce significant changes in the structure, physiology, and metabolism of the offspring. These changes could have important implications on food animal production especially if these perturbations impact muscle and adipose tissue development. Here, we evaluated the impact of different maternal isoenergetic diets, alfalfa haylage (HY; fiber), corn (CN; starch), and dried corn distillers grains (DG; fiber plus protein plus fat), on the transcriptome of fetal muscle and adipose tissues in sheep.', 'Prepartum diets were associated with notable gene expression changes in fetal tissues. In longissimus dorsi muscle, a total of 224 and 823 genes showed differential expression (FDR \u22640.05) in fetuses derived from DG vs. CN and HY vs. CN maternal diets, respectively. Several of these significant genes affected myogenesis and muscle differentiation. In subcutaneous and perirenal adipose tissues, 745 and 208 genes were differentially expressed (FDR \u22640.05), respectively, between CN and DG diets. Many of these genes are involved in adipogenesis, lipogenesis, and adipose tissue development. Pathway analysis revealed that several GO terms and KEGG pathways were enriched (FDR \u22640.05) with differentially expressed genes associated with tissue and organ development, chromatin biology, and different metabolic processes.",
            "output": [
                "Does maternal nutrition induce gene expression changes in fetal muscle and adipose tissues in sheep?"
            ]
        },
        {
            "id": "task847-61721a9c11a440dca3942ad701277e90",
            "input": "Premature ejaculation (PE) is the most common male sexual dysfunction. Its prevalence in Type 1 diabetes is unknown.', 'The aim of this study was to assess the prevalence of PE in Type 1 diabetes and the influence of glycemic control on ejaculatory function.', 'One hundred Type 1 diabetic male patients (age\\u2009<\\u200940 years) and 51 age-matched nondiabetic control subjects were evaluated for PE. A subgroup of 30 diabetic patients (20 with PE and 10 without) were also evaluated for blood glucose variability.', 'The presence of PE was assessed with the premature ejaculation diagnostic tool (PEDT) and the self-estimated intravaginal ejaculatory latency time (IELT). Glucose variability was evaluated by continuous glucose monitoring for a 7-day period with a DexCom G4 CGM system: the mean amplitude of glycemic excursions (MAGEs), low (LBGI) and high (HBGI) blood glucose indices, and the standard deviation of blood glucose (BGSD) were calculated.', 'PE prevalence did not differ significantly between the two groups: pathological values of the PEDT score (>8) and IELT score (<1 minute) were recorded in 24 out of 100 diabetic patients (24%) and in 12 out of 51 controls (23.5%). There were significant associations between hemoglobin A1c and the PEDT score (r\\u2009=\\u20090.27; P\\u2009=\\u20090.006) and IELT (r\\u2009=\\u2009-0.3; P\\u2009=\\u20090.01). In the subgroup assessed for glucose variability, the PEDT score was associated with LBGI (r\\u2009=\\u20090.43; P\\u2009=\\u20090.01), but not with BGSD (r\\u2009=\\u20090.1, P\\u2009=\\u20090.6), MAGE (r\\u2009=\\u2009-0.1; P\\u2009=\\u20090.4), or HBGI (r\\u2009=\\u20090.1; P\\u2009=\\u20090.6).",
            "output": [
                "Is premature ejaculation associated with glycemic control in Type 1 diabetes?"
            ]
        },
        {
            "id": "task847-e61294edc4ea4aa9afe3deff730afc73",
            "input": "We hypothesized that myocardial scar characterization using cardiac magnetic resonance imaging (CMR) may be associated with the occurrence of ventricular tachyarrhythmia (VT), appropriate implantable cardioverter-defibrillator (ICD) therapy and mortality.', 'Since a minority of patients with prophylactic ICD implantation receive appropriate ICD therapy, there is a need for more effective risk stratification for primary prevention in patients with ischemic cardiomyopathy.', \"In 99 patients with ischemic cardiomyopathy, CMR was performed prior to ICD implantation. We assessed if CMR indices (cardiac mass, LVEF) and CMR scar characteristics (infarct core mass, peri-infarction mass and the ratio's between left ventricular mass, infarct core mass and peri-infarction mass) were associated with outcome. The primary endpoint was sustained VT and/or appropriate ICD therapy. The secondary endpoint was all-cause mortality. During a median follow-up of 5.4 years (IQR 4.5-6.6 years), 34 patients reached the primary end-point (17 appropriate ICD shocks) and 26 patients died. In multivariable Cox regression analysis, peri-infarction to core-infarction ratio (HR 2.01, 95%CI: 1.17-3.44, p=0.01) was independently and significantly associated with the primary endpoint, whereas NYHA-class and lower LVEF were not. Conversely, age (HR 1.06, 95% CI: 1.01-1.12, p=0.02) and lower LVEF (HR 0.95, 95% CI: 0.91-1.00, p=0.04) were independently associated with all-cause mortality, mainly due to heart failure.",
            "output": [
                "Is myocardial scar characteristics based on cardiac magnetic resonance imaging associated with ventricular tachyarrhythmia in patients with ischemic cardiomyopathy?"
            ]
        },
        {
            "id": "task847-ba557150d3d94f588762978bdc24142b",
            "input": "To determine whether in-house patient-specific intensity modulated radiation therapy quality assurance (IMRT QA) results predict Imaging and Radiation Oncology Core (IROC)-Houston phantom results.', \"IROC Houston's IMRT head and neck phantoms have been irradiated by numerous institutions as part of clinical trial credentialing. We retrospectively compared these phantom results with those of in-house IMRT QA (following the institution's clinical process) for 855 irradiations performed between 2003 and 2013. The sensitivity and specificity of IMRT QA to detect unacceptable or acceptable plans were determined relative to the IROC Houston phantom results. Additional analyses evaluated specific IMRT QA dosimeters and analysis methods.\", 'IMRT QA universally showed poor sensitivity relative to the head and neck phantom, that is, poor ability to predict a failing IROC Houston phantom result. Depending on how the IMRT QA results were interpreted, overall sensitivity ranged from 2% to 18%. For different IMRT QA methods, sensitivity ranged from 3% to 54%. Although the observed sensitivity was particularly poor at clinical thresholds (eg 3% dose difference or 90% of pixels passing gamma), receiver operator characteristic analysis indicated that no threshold showed good sensitivity and specificity for the devices evaluated.",
            "output": [
                "Does institutional patient-specific IMRT QA predict unacceptable plan delivery?"
            ]
        },
        {
            "id": "task847-ea090d0032784c61a03a2ff868c68064",
            "input": "The DSM-5 encompasses a wide range of symptoms for Major Depressive Disorder (MDD). Symptoms are commonly added up to sum-scores, and thresholds differentiate between healthy and depressed individuals. The underlying assumption is that all patients diagnosed with MDD have a similar condition, and that sum-scores accurately reflect the severity of this condition. To test this assumption, we examined the number of DSM-5 depression symptom patterns in the \"Sequenced Treatment Alternatives to Relieve Depression\" (STAR*D) study.', 'We investigated the number of unique symptom profiles reported by 3703 depressed outpatients at the beginning of the first treatment stage of STAR*D.', 'Overall, we identified 1030 unique symptom profiles. Of these profiles, 864 profiles (83.9%) were endorsed by five or fewer subjects, and 501 profiles (48.6%) were endorsed by only one individual. The most common symptom profile exhibited a frequency of only 1.8%. Controlling for overall depression severity did not reduce the amount of observed heterogeneity.",
            "output": [
                "Is depression a consistent syndrome : An investigation of unique symptom patterns in the STAR*D study?"
            ]
        },
        {
            "id": "task847-12c2e51568344ec7ba60278e4036f560",
            "input": "The canals of Hering (CoH), which are the most peripherally located bile drainage pathway, are considered a niche of hepatic progenitor cells. Recently, CoH loss has been described as an early feature of primary biliary cirrhosis (PBC). We investigated the correlation between CoH loss and the histopathological variables of PBC.', 'Liver biopsy specimens from 62 PBC patients (M:F=8:54, age=58 \u00b1 12 years) were evaluated prior to ursodeoxycholic acid treatment. Liver biopsies of patients with normal liver (n=11), chronic viral hepatitis (n=36) and non-alcoholic fatty liver disease (n=13) were used as controls. The number of CoH per definite area of hepatic parenchyma (c to p ratio) was calculated in individual cases. We compared the c to p ratios of PBC patients with that of controls and analysed the correlations with histological variables and clinical features.', 'The c to p ratios in PBC patients with mild and extensive fibrosis were lower than those in controls with each degree of fibrosis. The c to p ratios were negatively correlated with stage, fibrosis, bile duct loss, orcein-positive granule deposition and hepatitis activities in PBC (p<0.01) and with alkaline phosphatase and total bilirubin levels at liver biopsies (p<0.05).",
            "output": [
                "Does canals of Hering loss relate to the progression of the histological stages of primary biliary cirrhosis?"
            ]
        },
        {
            "id": "task847-61a4d8906bd84fd8815c46e74210dd25",
            "input": "The ability of a treatment method to interfere with tinnitus-related neural activity patterns, such as cortical gamma rhythms, has been suggested to indicate its potential in relieving tinnitus. Therapeutic modulation of gamma-band oscillations with vagus nerve stimulation has been recently reported in epileptic patients. The aim of this study was to investigate the effects of transcutaneous vagus nerve stimulation (tVNS) on neural oscillatory patterns.', 'We calculated the power spectral density and synchrony of magnetoencephalography recordings during auditory stimulation in seven tinnitus patients and eight normal-hearing control subjects. Comparisons between subject groups were performed to reveal electrophysiological markers of tinnitus. tVNS-specific effects within each group were studied by comparing recording blocks with and without tVNS. We also investigated the correlation of each measure with individual ratings of tinnitus distress, as measured by the tinnitus handicap inventory questionnaire.', 'Tinnitus patients differed from controls in the baseline condition (no tVNS applied), measured by both cortical oscillatory power and synchronization, particularly at beta and gamma frequencies. Importantly, we found tVNS-induced changes in synchrony, correlating strongly with tinnitus handicap inventory scores, at whole-head beta-band (r = -0.857, p = 0.007), whole-head gamma-band (r = -0.952, p = 0.0003), and frontal gamma-band (r = -0.952, p = 0.0003).",
            "output": [
                "Does transcutaneous vagus nerve stimulation modulate tinnitus-related beta- and gamma-band activity?"
            ]
        },
        {
            "id": "task847-1eb40f252992485ab14df53bf645bf97",
            "input": "Lysophospholipids, particularly sphingosine 1-phosphate and lysophosphatidic acid, are known to be involved in the pathogenesis of atherosclerosis; however, the role of lysophosphatidylserine (LysoPS) in the onset of atherosclerotic diseases remains uncertain.', 'We investigated the effects of LysoPS on the uptake of oxidized low-density lipoprotein (oxLDL) and the modulation of inflammatory mediators and ER stress utilizing RAW264.7 cells and mouse peritoneal macrophages (MPMs).', 'We found that LysoPS augmented cholesterol accumulation in both models. Consistent with these findings, LysoPS increased the expression of scavenger receptors (CD36, MSR1, LOX1 and TLR4). Regarding the involvement of these lipids in inflammation, LysoPS significantly decreased the expression of inflammatory mediators in lipopolysaccharide (LPS)-treated RAW264.7 cells and MPMs. LysoPS also attenuated ER stress in LPS-untreated RAW264.7 cells. The expression patterns of LysoPS receptors differed considerably among the LPS-untreated RAW264.7 cells, LPS-treated RAW264.7 cells and MPMs.",
            "output": [
                "Does lysophosphatidylserine have Bilateral Effects on Macrophages in the Pathogenesis of Atherosclerosis?"
            ]
        },
        {
            "id": "task847-60bd65af3d554fe0a613f48df591c2eb",
            "input": "Various techniques and devices have been proposed for tricuspid valve (TV) repair in patients with tricuspid regurgitation (TR). However, residual or recurrent TR is not uncommon occurring in 20% to 30% of patients. This study reports first experiences with a new three-dimensional annuloplasty ring.', 'We retrospectively reviewed 200 consecutive patients who underwent TV repair for functional TR with the Contour 3D annuloplasty ring (Medtronic, Minneapolis, MN) from December 2010 to February 2013 at our institution. The follow-up is 98% complete (mean 1.0 \u00b1\\xa00.7 years; cumulative total 189 patient-years).', 'Mean age was 70.4 \u00b1 9.1 years and the median logistic European system for cardiac operative risk was 7%. Sixty-nine percent of the patients were in New York Heart Association class III/IV. Echocardiography documented moderate or severe TR in 97.5% of the patients, with a mean annulus diameter of 45.1 \u00b1 4.9 mm; 93.5% of the patients underwent a combined procedure, and 20.5% an urgent or emergent operation. The 30-day mortality was 6%. The preoperative TR grade was reduced from 2.45 \u00b1 0.53 to 0.77 \u00b1 0.54 (p < 0.001). At hospital discharge residual II TR or greater was present in 4.3% of the patients. Freedom from recurrent II TR or greater at 2\\xa0years was 90.9% \u00b1 4.2% and freedom from TV-related reoperations at 2 years was 98.5% \u00b1 1.0%. No case of\\xa0ring dehiscence occurred. Fourteen patients (7%) required a permanent pacemaker implantation for atrioventricular block.",
            "output": [
                "Does early experience with a new three-dimensional annuloplasty ring for the treatment of functional tricuspid regurgitation?"
            ]
        },
        {
            "id": "task847-ba65d7e82a004590a386b68ba1494514",
            "input": "We aimed to study the association between cytomegalovirus (CMV) infection and hypertension in Kazakh and Han populations from Xinjiang Province, China.', 'We analyzed data on 800 Kazakhs (467 hypertension patients and 333 healthy control participants) and 800 Hans (482 hypertension patients and 318 healthy control participants) aged 18-84 years old. ELISA and real-time quantitative PCR coupled with restriction fragment length polymorphism analysis were applied for determining CMV infection and glycoprotein B (gB) genotypes, respectively.', 'Serologic evidence of CMV infection was obtained for 95.4% and 90.1% of the Kazakhs and Hans, respectively. The CMV seroprevalence rates among the Kazakh and Han participants with hypertension were 96.8% and 89.8%, respectively. Multiple logistic regression analyses revealed statistically significant independent associations between CMV seropositivity and hypertension in Kazakh males and between CMV antibody titers and hypertension in Hans; significant relationships also existed between CMV antibody titers and blood pressure in Hans. In Kazakhs, 3 CMV gB genotypes were identified: gB2 and genotype mixtures gB1+gB2 and gB2+gB3. In Hans, 4 CMV gB genotypes were identified: gB1, gB2, gB1+gB2, and gB2+gB3. Of the 4 studied genotypes, gB2+gB3 showed a significant independent association with hypertension in Kazakh females.",
            "output": [
                "Is human cytomegalovirus infection associated with essential hypertension in Kazakh and Han Chinese populations?"
            ]
        },
        {
            "id": "task847-a706d914dce942c18aff5b2cbb0eea4b",
            "input": "Understanding the dynamics of the gut-brain axis has clinical implications for physical and mental health conditions, including obesity and anxiety. As such disorders have early life antecedents, it is of value to determine if associations between the gut microbiome and behavior are present in early life in humans.', 'We used next generation pyrosequencing to examine associations between the community structure of the gut microbiome and maternal ratings of child temperament in 77 children at 18-27months of age. It was hypothesized that children would differ in their gut microbial structure, as indicated by measures of alpha and beta diversity, based on their temperamental characteristics.', 'Among both boys and girls, greater Surgency/Extraversion was associated greater phylogenetic diversity. In addition, among boys only, subscales loading on this composite scale were associated with differences in phylogenetic diversity, the Shannon Diversity index (SDI), beta diversity, and differences in abundances of Dialister, Rikenellaceae, Ruminococcaceae, and Parabacteroides. In girls only, higher Effortful Control was associated with a lower SDI score and differences in both beta diversity and Rikenellaceae were observed in relation to Fear. Some differences in dietary patterns were observed in relation to temperament, but these did not account for the observed differences in the microbiome.",
            "output": [
                "Is gut microbiome composition associated with temperament during early childhood?"
            ]
        },
        {
            "id": "task847-671b37ffbb504edc8d0dd4a80af73d18",
            "input": "The interaction between Siglec-10 and its ligand, CD24, selectively represses tissue damage-caused immune responses. However, the nature of Siglec-10 and CD24 in human hepatocellular carcinoma (HCC) is still poorly defined. Hereon, the expression, function, and regulation of CD24 and Siglec-10 in HCC were investigated in the present study.', 'Flow cytometry was performed to examine the expression of Siglec-10 in HCC tissues and adjacent non-tumor tissues of HCC patients. To further determine whether Siglec-10 expression is associated with the clinical characteristics and survival, conventional immunohistochemistry was performed in 96 HCC patients. Additionally, the role of Siglec-10 in the regulation of natural killer (NK) cell dysfunction was evaluated. Finally, CD24 expression in HCC was also assessed.', 'Siglec-10 was expressed most on NK cells in HCC (40.7 \u00b1 4.5%). Compared with surrounding non-tumor tissues, tumor tissues had higher Siglec-10 expression (31.0 \u00b1 1.7% versus 40.7 \u00b1 4.5%, n = 10, P < 0.05), and the expression was negatively associated with patient survival. Siglec-10(+)CD56(+) NK cells exhibited reduced effector function, as shown by decreased granules and cytokine expressions compared with Siglec-10(-)CD56(+) NK cells. Moreover, the number of CD24(+)CD45(-) cells in HCC tissues was higher than that in adjacent non-tumor tissues (9.4 \u00b1 0.9% versus 3.1 \u00b1 0.9%, n = 15, P < 0.05).",
            "output": [
                "Is siglec-10 associated with survival and natural killer cell dysfunction in hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-13dc982c0d9b4a878472149f5efe3012",
            "input": "Postoperative cognitive dysfunction is increasingly recognized as an important clinical syndrome. Inhalation anesthetics are commonly used during surgery, and it has been proposed that inhalation anesthetics impair cognitive function. However, there are few clinical interventions and treatments available to prevent this disorder. GTS-21, a selective agonist of alpha 7 nicotinic acetylcholine receptor, has been indicated to exert neuroprotective effects in the experimental animal models of neurodegenerative diseases. Therefore, we hypothesized that pretreatment with GTS-21 attenuates isoflurane-induced cognitive decline in aged rats.', 'In the present study, 20-mo-old rats were administered GTS-21 or an equal volume of saline by intraperitoneal injection 30 min before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Spatial learning and memory of the rats were assessed at 2 wk after isoflurane exposure. The expression levels of interleukin (IL)-1\u03b2, IL-6, and tumor necrosis factor-\u03b1 in the hippocampus and cerebral cortex were determined by enzyme-linked immunosorbent assay. Simultaneously, neuronal apoptosis in the hippocampus was also observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and Nissl staining.', 'We found that exposure to isoflurane induces learning and memory deficits of old rats. IL-1\u03b2 in the hippocampus was increased at 4 h after isoflurane exposure. Isoflurane also increased neuroapoptosis in the hippocampus and decreased neuronal density in the CA1 region. And GTS-21 pretreatment effectively alleviated these changes.",
            "output": [
                "Does alpha 7 nicotinic acetylcholine receptor agonist GTS-21 mitigate isoflurane-induced cognitive impairment in aged rats?"
            ]
        },
        {
            "id": "task847-5a73372cd0d84b03a27f7e904a2f66b0",
            "input": "Malignant melanoma is an aggressive form of skin cancer with limited effective therapeutic options. Melanoma research concentrates on maximizing the effect on cancer cells with minimal toxicity to normal cells. AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis and has been shown to control tumor progression regulating the cell cycle, protein synthesis, and cell growth and/or survival. Honokiol (HNK) is a biphenolic compound derived from Magnolia officinalis, a plant that has been used in traditional Chinese and Japanese medicine for the treatment of various pathological conditions. Recent studies have shown that HNK has antitumor activity with relatively low toxicity. In this study, we demonstrated that the growth inhibitory effects of HNK on melanoma and melanoma cancer stem cells were mediated through the activation of AMPK and hence AMPK signaling in melanoma cells.', 'We determined the effects of HNK treatment on various melanoma cell lines. HNK-induced cell growth inhibitory effects were determined using hexosaminidase assay. Protein expression studies were done by immunoblotting. Primary spheroid assay was used to assess stemness by growing single suspension cells in ultralow attachment plates.', 'HNK is highly effective in inhibiting melanoma cells by attenuating protein kinase B/mammalian target of rapamycin and AMPK signaling. HNK showed significant inhibition of the spheroid-forming capacity of melanoma cells and, hence, stemness. HNK significantly decreased the number and size of melanospheres in a dose-dependent manner. Western blot analyses showed enhanced phosphorylation of AMPK in melanoma cells. Furthermore, HNK decreased the cellular adenosine triphosphate pool in a dose-dependent manner with maximum effects observed at 48\\xa0hours.",
            "output": [
                "Does honokiol affect melanoma cell growth by targeting the AMP-activated protein kinase signaling pathway?"
            ]
        },
        {
            "id": "task847-2d6ebdb401124510b38fdfa030185306",
            "input": "To evaluate the visual and anatomical outcomes of dexamethasone intravitreal implant (DXI; 700\\u2005\u03bcg, Ozurdex; Allergan, Irvine, California, USA) as adjunctive therapy for patients with refractory wet age-related macular degeneration (AMD).', 'Retrospective review of the medical records of seven patients (seven eyes) who initially responded well to intravitreal ranibizumab but subsequently developed persistent intra/sub-retinal fluid (IRF/SRF) and underwent a single injection of DXI, between May 2012 and May 2013. Two weeks after DXI, the patients continued with their monthly ranibizumab injections. Best corrected visual acuity (BCVA) logarithm of the minimum angle of resolution (logMAR) and central retinal thickness (CRT) were recorded at baseline, 2\\u2005weeks, 6\\u2005weeks, 3\\u2005months and 6\\u2005months after DXI injection. Complications were recorded too.', 'All patients had at least 24\\u2005months of ranibizumab treatment. Mean age was 81.5\u00b15.8\\u2005years. At baseline, mean BCVA was 0.53\u00b10.13 logMAR (20/70 Snellen) and mean CRT was 273.14\u00b150.94\\u2005\u03bcm. BCVA did not change significantly after DXI over the follow-up period. However, all eyes had lost fewer than 0.3\\u2005logMAR units. Complete resolution of the persistent IRF/SRF was achieved in five eyes (71.4%) at 6\\u2005weeks, and remained stable at 3\\u2005months. Two weeks after DXI injection, the mean CRT diminished compared with baseline (248.28\u00b131.8\\u2005\u00b5m; p=0.03) and the greatest reduction was observed at 3\\u2005months after DXI injection (241.5\u00b136.6\\u2005\u00b5m; p=0.04). Progression of lens opacity was detected in one case (50% of phakic eyes). Retreatment with DXI was performed in two eyes.",
            "output": [
                "Do dexamethasone intravitreal implant as adjunct therapy for patients with wet age-related macular degeneration with incomplete response to ranibizumab?"
            ]
        },
        {
            "id": "task847-b36ad20bb1ff4be2855cdf44f2b06e88",
            "input": "Time to achieve target temperature varies substantially for patients who undergo targeted temperature management (TTM) after cardiac arrest. The association between arrival at target temperature and neurologic outcome is poorly understood. We hypothesized that shorter time from initiation of cooling to target temperature (\"induction\") will be associated with worse neurologic outcome, reflecting more profound underlying brain injury and impaired thermoregulatory control.', 'This was a multicenter retrospective study analyzing data from the Penn Alliance for Therapeutic Hypothermia (PATH) Registry. We examined the association between time from arrest to return of spontaneous circulation (ROSC) (\"downtime\"), ROSC to initiation of TTM (\"pre-induction\") and \"induction\" with cerebral performance category (CPC).', 'A total of 321 patients were analyzed, of whom 30.8% (99/321) had a good neurologic outcome. Downtime for survivors with good outcome was 11 (IQR 6-27) min vs. 21 (IQR 10-36) min (p=0.002) for those with poor outcome. Pre-induction did not vary between good and poor outcomes (98 (IQR 36-230) min vs. 114 (IQR 34-260) (p=ns)). Induction time in the good outcome cohort was 237 (IQR 142-361) min compared to 180 (IQR 100-276) min (p=0.004). Patients were categorized by induction time (<120min, 120-300min, >300min). Using multivariable logistic regression adjusted for age, initial rhythm, and downtime, induction time >300min was associated with good neurologic outcome when compared to those with an induction time <120min.",
            "output": [
                "Is shorter time to target temperature associated with poor neurologic outcome in post-arrest patients treated with targeted temperature management?"
            ]
        },
        {
            "id": "task847-b8dd31fb5cf149e490636c9c9ef8a11d",
            "input": "Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on the cardiac muscle. Here we studied the effects of prolonged (24 \u00b1 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and IL-6.', 'We measured sarcomere shortening (SS) and cellular calcium (Ca(2+)) transients (\u0394Cai, with fura-2 AM) in isolated cardiomyocytes externally paced at 5 Hz at 37\u00b0C.', 'SS decreased after incubation with LPS (100 \u03bcg/mL), IL-1 (100 ng/mL), and IL-6 (30 ng/mL), but not with lesser doses of these mediators, or TNF (10-100 ng/mL). A combination of LPS (100 \u03bcg/mL), TNF, IL-1, and IL-6 (each 100 ng/mL; i.e., \"Cytomix-100\") induced a maximal decrease in SS and \u0394Cai. Sarcoplasmic reticulum (SR) Ca(2+) load (CaSR, measured with caffeine) was unchanged by Cytomix-100; however, SR fractional release (\u0394Cai/CaSR) was decreased. Underlying these effects, Ca(2+) influx into the cell (via L-type Ca(2+) channels, LTCC) and Ca(2+) extrusion via Na(+)/Ca(2+) exchange were decreased by Cytomix-100. SR Ca(2+) pump (SERCA) (SR Ca(2+) ATPase) was not affected.",
            "output": [
                "Do lipopolysaccharide and cytokines inhibit rat cardiomyocyte contractility in vitro?"
            ]
        },
        {
            "id": "task847-1c2cfdee7d024923af9971292f817301",
            "input": "Oxidative stress causes the defects of retinal pigment epithelial (RPE) cells that contribute to age-related macular degeneration (AMD). This study was conducted to determine whether wogonin could prevent H2O2-induced oxidative stress in RPE cells.', 'A RPE cell line, ARPE-19, was obtained for the cell model. ARPE-19 cells were pre-treated with various concentrations of wogonin for 24 h before being exposed to H2O2 for 2 h to induce oxidative stress. Cell metabolic activity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was quantified by the flow cytometry. Protein level was assed by western blot.', 'The RPE cells exposed to to 200 mM H2O2 demonstrated a significant depression in the cell viability; whereas pre-treatment with 50 and 100 mmol/l wogonin could significantly improve the cell viability in a dose-dependent manner. The proportion of PI-positive cells was increased significantly in RPE cells treated with H2O2 alone; whereas pretreatment with 100 mM wogonin significantly reduced H2O2 -induced RPE cell death rate. In protein level, the wogonin use could reduce the level of p-Akt significantly and this is the possible mechanism of the antioxidant effect of wogonin.",
            "output": [
                "Does wogonin modulate hydroperoxide-induced apoptosis via PI3K/Akt pathway in retinal pigment epithelium cells?"
            ]
        },
        {
            "id": "task847-b99ac2eef683470f953d98891a02c18c",
            "input": "To determine whether recent reimbursement cuts have resulted in a shift of outpatient MRI from private offices to hospital outpatient departments (HOPDs); and to study office MRI utilization trends among radiologists and other specialists.', 'The Medicare Part B Physician/Supplier Procedure Summary Master Files were used. MRI codes were aggregated, and total MRI volumes from 2002 to 2012 were studied. Medicare place-of-service codes were used to identify studies performed in private offices and HOPDs and create trend lines. Specialty codes were used to categorize private office MRI users as radiologists, orthopedic surgeons, other physicians, and independent diagnostic testing facilities.', 'Medicare office and HOPD utilization of MRI (all specialties) rose rapidly from 2002 to 2006, reaching 2,727,807 in offices and 2,355,641 in HOPDs. Thereafter, office volume steadily declined, whereas HOPD volume steadily increased. By 2012, more studies were done in HOPDs than in offices. Over the entire period from 2002 and 2012, office MRI volume among radiologists increased 27%, compared with 216% among orthopedic surgeons and 124% among other physicians.",
            "output": [
                "Do trends in outpatient MRI seem to reflect recent reimbursement cuts?"
            ]
        },
        {
            "id": "task847-a119f30c917441ccbf4304b5c2d36d51",
            "input": "To investigate the incidence of acute kidney injury after cardiac surgery and its association with mortality in a patient population receiving ibuprofen and gentamicin perioperatively.', 'Retrospective study with Cox regression analysis to control for possible preoperative, intraoperative and postoperative confounders.', 'University hospital-based single-center study.', 'All patients who underwent coronary artery bypass grafting \u00b1 valve surgery during 2012.', 'None.', 'Acute surgery within 24 hours of coronary angiography, previous nephrectomy, preoperative sCr >2.26 mg/dL and selective cerebral perfusion during cardiopulmonary bypass were used as exclusion criteria. Acute kidney injury was defined, using the Acute Kidney Injury Network (AKIN) criteria. Six hundred eight patients were included in the study. Mean age was 68.2 \u00b1 9.7 years, and 81% were males. Acute kidney injury was seen in 28.1% of the patients. Overall mortality at one year was 7% and 3% in the no-AKI group. At one year, mortality was 15% in patients with AKIN stage 1 and AKIN stage 2 compared to 70% in AKIN stage 3. A hazard ratio of 2.34 (95% CI: 1.21-4.51, p = 0.011) and 5.62 (95% CI: 2.42-13.06), p<0.0001) were found for AKIN stage 1 and 2/3 combined, respectively.",
            "output": [
                "Is acute kidney injury independently associated with higher mortality after cardiac surgery?"
            ]
        },
        {
            "id": "task847-e106d387230145ee9f8d23410b359d15",
            "input": "The human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells.', 'The level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(-) cells).', 'The level of RECQL1 expression was not related to histological type, clinical stage, or retroperitoneal lymph node metastasis, but the expression level was significantly higher (P\\u2009=\\u20090.002) in patients with recurrence than those without recurrence, and progression-free survival and complete response rate to chemotherapy were also improved in patients with RECQL1-low expression (n = 39) stage III/IV EOC (P = 0.02 and P <0.05 vs RECQL1-high expression patients (n = ), respectively). A cell proliferation and colony formation assays revealed significantly less growth of RECQL1(-) cells compared to RECQL1(+) cells. A flow cytometry using annexin V -FITC and propidium iodide (PI) staining revealed a significant increase in apoptotic RECQL1(-) cells. Cell cycle analysis showed a significantly greater distribution in subG1 phase indicating apoptotic cells in RECQL1(-) cells than in RECQL1(+) cells.",
            "output": [
                "Is the level of RECQL1 expression a prognostic factor for epithelial ovarian cancer?"
            ]
        },
        {
            "id": "task847-d78bdcd602f24ce4bc3a6c39c28e94d5",
            "input": "To explore the relationship between continuous thrombocytopenia and sepsis in patients with severe burns.', 'Clinical data of 148 severely burned patients admitted to our,two burn centers from January 2007 to December 2011 and conforming to the study criteria were retrospectively analyzed. All patients were divided into sepsis group (n =44) and non-sepsis group (n = 104) according to the presence or absence of sepsis within post burn day (PBD) 30. The data of age, gender, total burn area, full-thickness burn area, fluid infusion volume within post burn hour (PBH) 24, plasma concentration of calcium ion on PBD 1, plasma concentration of albumin on PBD 1, platelet count on PBD 1, acute physiology and chronic health evaluation (APACHE) II score on admission, the presence or absence of hypovolemic shock or inhalation injury on admission, the presence or absence of disseminated intravascular coagulation (DIC) within PBH 48, operation or no operation within PBD 3, thrombocytopenia duration within PBD 10, and mortality were statistically compared between two groups to screen the independent risk factors of sepsis. Data were processed with t test, chi-square test, single factor Logistic regression analysis, and multi-factor Logistic regression analysis.', 'Between two groups, there were statistically significant differences in total burn area, full-thickness burn area, plasma concentration of calcium ion on PBD 1, plasma concentration of albumin on PBD 1, APACHE II score on admission, presence or absence of hypovolem- ic shock on admission, presence or absence of inhalation injury on admission, presence or absence of DIC within PBH 48, and mortality (with t values from 2.433 to 4.082, \u03c72 values from 8. 818 to 31.528, P < 0.05 or P < 0.01). Furthermore, the duration of thrombocytopenia within PBD 10 in sepsis group was (5.2 \u00b1 2.4) d, which was significantly longer than that in non-sepsis group [(2.9 \u00b1 1.9) d, t =6. 189, P <0.01]. There were no statistically significant differences in the other indexes between two groups (with t values from 0.971 to 1. 250, \u03c72 values respectively 0. 054 and 1.529, P values above 0.05). Single factor and multi-factor Logistic regression analysis indicated that APACHE II score on admission and duration of thrombocytopenia within PBD 10 were closely related to occurrence of sepsis (with odds ratio respectively 1. 140 and 1.569, P values below 0.01).",
            "output": [
                "Do [ Clinical significance of continuous thrombocytopenia in predicting sepsis after severe burn ]?"
            ]
        },
        {
            "id": "task847-0b3536be2bee482285fcf61905920bab",
            "input": "Peripheral arterial disease (PAD) is common in patients with acute cerebral ischemia. Indexes of resistance derived from the systolic and diastolic velocities are routinely used in diagnostic transcranial Doppler (TCD) to detect intracranial arterial disease. We sought to explore whether these indexes can predict the presence of PAD in acute cerebral ischemia.', 'We prospectively evaluated consecutive patients with acute cerebral ischemia. On TCD, peak-systolic and end-diastolic velocities in both middle cerebral and basilar arteries were manually measured to calculate pulsatility index (PI) and resistance index (RI). Increased resistance was defined as PI equal to 1.2 or more and RI equal to .75 or more. Ankle-brachial index (ABI) measurements were performed and an ABI equal to .9 or more was considered predictive of definite PAD.', 'We included 95 patients (45 male, 50 female) aged 66 \u00b1 9 years with a median National Institutes Health Stroke Scale score of 3 (interquartile range, 8) points. The ABI was abnormal and consistent with definite PAD in 24 of 95 (25.3%; 95% confidence interval [CI], 16.4-34.2) patients. Increased PI did not differ among patients with and without PAD (20.8% vs. 28.2%, P = .60). Only 1 patient with PAD had increased RI as opposed to 4 patients without PAD (4.2% vs. 5.6%, P = 1.0). Increased PI was not found to be an independent predictor of PAD (odds ratio [OR], .68; 95% CI, .22-2.12; P = .51). Increases in both PI and RI independently predicted arterial hypertension (OR, 1.62; 95% CI, 1.19-2.21; P = .002 and OR, 3.20; 95% CI, 1.51-6.77; P = .002, respectively).",
            "output": [
                "Does increased pulsatility of the intracranial blood flow spectral waveform on transcranial Doppler point to peripheral arterial disease in stroke patients?"
            ]
        },
        {
            "id": "task847-e316440d1c234dd5b2de4038bd0074f1",
            "input": "The etiology of idiopathic scoliosis remains unknown, but growth is a risk factor for progression. Growth pattern differs in children with and without scoliosis. Cartilage oligomeric matrix protein (COMP) may be associated with scoliosis and growth. We, therefore, studied COMP in children with and without idiopathic scoliosis.', 'We included 105 children, with mean age 14.4 years (range 10-16), under observation or treatment for idiopathic scoliosis, and 103 children from an age-matched population-based cohort. COMP was measured in serum at the time of inclusion. Growth velocity was estimated from repeated height measurements. T tests, analysis of covariance or linear regression were used for statistical comparisons.', 'COMP was mean (SD) 11 (5) units/liter (U/L) in children with scoliosis and 13 (5) U/L in the control cohort (p = 0.005, adjusted for sex and sampling time of the day). When patients and controls were analyzed together, high COMP was correlated with high growth velocity (\u03b2 = 0.19, p = 0.003). When patients and controls were analyzed separately, COMP was correlated with growth velocity in children with scoliosis (\u03b2 = 0.27, p = 0.007), but not in children without scoliosis (\u03b2 = 0.02, p = 0.83) (all analyses adjusted for age, sex and sampling time). Low COMP was significantly correlated with large curve size in children with scoliosis (\u03b2 = -0.29, p = 0.003), but not after adjustment for age, sex and sampling time (\u03b2 = -0.16; p = 0.14).",
            "output": [
                "Is serum level of cartilage oligomeric matrix protein lower in children with idiopathic scoliosis than in non-scoliotic controls?"
            ]
        },
        {
            "id": "task847-1a681be0b0384a4b82bdfd1db73a4f67",
            "input": "Acute kidney injury (AKI) is an established indicator of all-cause mortality in a coronary care unit (CCU), and evaluating the risks of renal dysfunction can guide treatment decisions. In this study we used the Society of Thoracic Surgeons (STS) score to predict the incidence of AKI in CCU patients who had not undergone coronary artery bypass surgery (CABG) after a cardiac angiogram.', 'The study cohort comprised 126 patients diagnosed with 2 or 3 coronary vessels disease who did not receive CABG during their hospital course. This study was performed in the CCU of a tertiary referral university hospital between September 2012 and August 2013. The STS score was evaluated with adjustment in all patients and the outcomes of the risk of mortality, morbidity, or mortality and renal failure were selected for predicting assessment. Furthermore, the performance of the STS scores was compared with that of other scoring systems.', 'A total of 28.5% (36 of 126) of the patients had AKI of varying severity. For predicting AKI, the STS renal failure score was excellent, with areas under the receiver operating characteristic curve of 0.851 \u00b1 0.039, p < 0.001. When compared with other scoring systems, the STS renal failure score demonstrated the highest discriminatory power, the most favorable Youden index, and the highest overall correctness of prediction.",
            "output": [
                "Do society of Thoracic Surgeons score predicts kidney injury in patients not undergoing bypass surgery?"
            ]
        },
        {
            "id": "task847-2cf6902c45a6459681c16183ccc52ea3",
            "input": "Stuttering priapism (SP) is seen in sickle cell disease (SCD) and characterized by short-lived painful erections. Imbalanced vascular tone is the postulated cause and this may be reflected in changes in baseline penile blood flow as measured using penile Doppler ultrasound (PDU).', 'The aim of this study was to investigate the baseline penile blood flow characteristics in men with SCD and SP, by comparing with men without SP.', \"PDU findings were retrospectively analyzed in 100 men during flaccid state. Nine men had SP (age range 20-40 years), 4 had Peyronie's disease (PD) (35-48 years), 67 men had erectile dysfunction (16-67 years), and 20 men had normal erectile function (18-42 years).\", 'The variables measured were peak systolic and end-diastolic velocities, and the Doppler velocity waveform. Values in men with SP were compared with those in the other groups.', 'Median systolic and diastolic velocity was significantly higher in men with SP (systolic/diastolic velocity was 26/4\\u2009cm/second in men with SP vs. 13/0\\u2009cm/second, 14/0\\u2009cm/second, and 16/0\\u2009cm/second in men with PD, ED, and normal erectile function, respectively; P=0.0001). Men with SP had a characteristic low peripheral resistance (PR) waveform with fluctuating velocities; the diastolic velocity was consistently positive (2-7\\u2009cm/second) and fluctuated between +2 and +8\\u2009cm/second. In comparison, the other 91 men had high PR waveform and consistently negative diastolic velocity (range 0 to -2\\u2009cm/second).",
            "output": [
                "Is penile Doppler ultrasound in men with stuttering priapism and sickle cell disease -- a labile baseline diastolic velocity a characteristic finding?"
            ]
        },
        {
            "id": "task847-13d4a2bc44e84d88927d9e0f676aa6dc",
            "input": "Cardiovascular risk factors, including diabetes mellitus may attenuate the cardioprotection by postconditioning. This study aimed to investigate the cardioprotective effect of ischemic-postconditioning (IPostC) against ischemia/reperfusion injury in normal and chronically type-1 diabetic rats and the effect of mitochondrial permeability transition pore (mPTP) inhibition in this field.', 'Diabetes was induced by a single intra-peritoneal injection of streptozotocin (50\\xa0mg/kg) in Wistar male rats (250-300\\xa0g). After 8\\xa0weeks, the hearts of control and diabetic animals were isolated and mounted on a constant-pressure Langendorff apparatus. All hearts were subjected to 30\\xa0min regional ischemia followed by 45\\xa0min reperfusion (by occluding and re-opening of LAD coronary artery, respectively). At the end of ischemia, the hearts received IPostC, cyclosporine-A, or both or none of them. Myocardial creatine-kinase (CK) release as an index of tissue injury was measured spectrophotometery in coronary effluent in reperfusion phase. Infarct size was identified by triphenyltetrazolium chloride staining. Heart rate, left ventricular end-diastolic pressure (LVEDP), LV systolic pressure (LVSP), rate-pressure product (RPP) and coronary flow were recorded throughout the experiment.', 'IPostC, applied at the onset of reperfusion, failed to improve myocardial LVEDP and RPP, or reduce tissue damage indicated by infarct size and CK release in diabetic hearts, while it significantly recovered these parameters toward the pre-ischemic values in control hearts (P\\u2009<\\u20090.05). In contrast, with simultaneous inhibition of mPTP using cyclosporine-A, the cardioprotective effects of IPostC on myocardial hemodynamics, infarct size and CK release were significantly restored in diabetic hearts (P\\u2009<\\u20090.05).",
            "output": [
                "Does inhibition of mitochondrial permeability transition pore restore the cardioprotection by postconditioning in diabetic hearts?"
            ]
        },
        {
            "id": "task847-ebbb36f95da242588b04db80f543cc54",
            "input": "Studies on the use of intradetrusor botulinum toxin A injection for children with neuropathic bladders are insufficient and the results are controversial. The aim of the present study was to evaluate the effect of intradetrusor botulinum toxin A injection for children with neuropathic bladders that are resistant to anticholinergic treatment, and to reveal any criteria indicating treatment success.', 'Hospital records were reviewed of 16 children with neuropathic bladders due to myelomeningocele, and who had botulinum toxin A injections between 2007 and 2010. Botulinum toxin A (10 units/kg) was injected endoscopically into various sites of the detrusor, except the trigone. The success was defined as complete dryness between clean intermittent catheterizations. Urodynamic studies before and after the application were evaluated and parameters, including bladder capacity (measured/expected) and compliance, were also analyzed. Reviewing the results, patients were then classified into two groups: as having fibrotic bladders (noncompliant, acontractile bladders with high pressures) or overactive bladders. Urodynamic findings and therapy success were then compared between the groups.', 'A total of 19 injections, including repeat injections in three patients, were performed. Results of the 16 initial injections were evaluated. Nine patients had detrusor overactivity, and five out of nine (56%) applications in this group resulted in complete dryness between clean intermittent catheterizations. In bladders with typical detrusor overactivity, there was a significant increase in both the capacity (from 0.53 to 0.74) and compliance (from 4.7 to 8.6 ml/cm H2O). Looking at the seven patients that displayed fibrotic bladders with very low compliance and no contraction at all, none of them presented with notable clinical improvement from injections. Comparing the urodynamic findings, there was no significant difference in compliance (3.1 ml/cm H2O before and 3.5 ml/cm H2O after) and bladder capacity (0.58 before and 0.52 after the treatment) in the fibrotic bladders.",
            "output": [
                "Is botulinum injection useless on fibrotic neuropathic bladders?"
            ]
        },
        {
            "id": "task847-db548d59a0bf454dbda0ec7fd11249f6",
            "input": "Advanced heart failure (HF) is associated with increased morbidity and mortality; traditionally used prognostic factors often fail to predict the outcome. Increased red blood cell distribution width (RDW) has recently been recognized as an important unfavorable prognostic factor in HF, independent of anemia; however, the role of RDW in patients with advanced HF has not yet been investigated.', 'Eighty consecutive patients with stage D heart failure, recently hospitalized for HF decompensation, were enrolled. A Cox proportional-hazard model was used to determine whether RDW was independently associated with outcome.', 'At study entry, ejection fraction (EF), pulmonary capillary wedge pressure (PCWP), hemoglobin (Hb) and RDW were 25 \u00b1 8.6%, 27.5 \u00b1 8 mmHg, 12.5 \u00b1 1.9 mg/dL and 18 \u00b1 3.5% (normal <14.5%) respectively. At 6 months, 44 patients (55%) had died. In this patient population, EF (p=0.45), PCWP (p=0.106), age (p=0.54), albumin (0.678), iron (p=0.37), creatinine (p=0.432), iron deficiency defined by bone marrow aspiration (p=0.37), bilirubin (p=0.422), peak VO2 (p=0.057) and Hb (p=0.95) were not significant predictors of a worse outcome. However, RDW was a significant marker for adverse prognosis (p=0.007, HR: 1.14, CI: 1.04-1.24) and retained its prognostic significance even when corrected for Hb values (HR: 1.15, CI: 1.05-1.27, p=0.003).",
            "output": [
                "Is red blood cell distribution width a significant prognostic marker in advanced heart failure , independent of hemoglobin levels?"
            ]
        },
        {
            "id": "task847-8fe0f700a42f4d60862076c80fa81975",
            "input": "The aim of this study was to examine recent trends in imaging utilization in emergency departments (EDs) in the Medicare population.', \"The 2002 to 2012 Medicare Part B databases were used. Imaging studies were categorized by modality. Medicare's place-of-service codes identified those studies performed in ED patients. Specialty codes identified the specialties of the interpreting physicians. Utilization rates per 1,000 Medicare beneficiaries were calculated. Trends were assessed in plain radiography (XR), CT, noncardiac ultrasound, MRI, and nuclear medicine.\", 'XR and CT were the most widely used modalities in ED patients. From 2002 to 2012, the XR utilization rate per 1,000 increased from 248.7 to 320.0 (+29%), and CT increased from 57.2 to 147.9 (+159%). Utilization rates of the other modalities were much lower. Ultrasound increased from 9.5 to 21.0 (+121%), while MRI increased from 1.4 to 5.1 (+264%). Growth in these 4 modalities was continuous and did not show the flattening that has characterized the utilization trends in other places of service. Nuclear medicine use was very low and remained essentially flat. During the study period, CT accrued 91 new examinations per 1,000, followed by XR at 71 and ultrasound at 11.5. The vast majority of examinations were interpreted by radiologists.",
            "output": [
                "Is continued growth in emergency department imaging bucking the overall trends?"
            ]
        },
        {
            "id": "task847-5813faf01bed4ee39ba624b74a09aaba",
            "input": "CD100, also known as Sema4D, is a member of the semaphorin family and has important regulatory functions that promote immune cell activation and responses. The role of CD100 expression on B cells in immune regulation during chronic hepatitis C virus (HCV) infection remains unclear.', 'We longitudinally investigated the altered expression of CD100, its receptor CD72, and other activation markers CD69 and CD86 on B cells in 20 chronic HCV-infected patients before and after treatment with pegylated interferon-alpha (Peg-IFN-\u03b1) and ribavirin (RBV) by flow cytometry.', 'The frequency of CD5+ B cells as well as the expression levels of CD100, CD69 and CD86 was significantly increased in chronic HCV patients and returned to normal in patients with sustained virological response after discontinuation of IFN-\u03b1/RBV therapy. Upon IFN-\u03b1 treatment, CD100 expression on B cells and the two subsets was further up-regulated in patients who achieved early virological response, and this was confirmed by in vitro experiments. Moreover, the increased CD100 expression via IFN-\u03b1 was inversely correlated with the decline of the HCV-RNA titer during early-phase treatment.",
            "output": [
                "Is cD100 up-regulation induced by interferon-\u03b1 on B cells related to hepatitis C virus infection?"
            ]
        },
        {
            "id": "task847-da010a4b78ab44c3bbf5a75487c65130",
            "input": "Acute promyelocytic leukemia (APL) is a sub-type of acute myeloid leukemia (AML) characterized by a block of myeloid differentiation at the promyelocytic stage and the predominant t(15:17) chromosomal translocation. We have previously determined that cells from APL patients show increased expression of genes regulated by hypoxia-inducible transcription factors (HIFs) compared to normal promyelocytes. HIFs regulate crucial aspects of solid tumor progression and are currently being implicated in leukemogenesis.', \"To investigate the contribution of hypoxia-related signaling in APL compared to other AML sub-types, we reverse engineered a transcriptional network from gene expression profiles of AML patients' samples, starting from a list of direct target genes of HIF-1. A HIF-1-dependent subnetwork of genes specifically dysregulated in APL was derived from the comparison between APL and other AMLs.\", 'Interestingly, this subnetwork shows a unique involvement of genes related to extracellular matrix interaction and cell migration, with decreased expression of genes involved in cell adhesion and increased expression of genes implicated in motility and invasion, thus unveiling the presence of characteristics of epithelial-mesenchymal transition (EMT). We observed that the genes of this subnetwork, whose dysregulation shows a peculiar pattern across different AML sub-types, distinguish malignant from normal promyelocytes, thus ruling out dependence on a myeloid developmental stage. Also, expression of these genes is reversed upon treatment of APL-derived NB4 cells with all-trans retinoic acid and cell differentiation.",
            "output": [
                "Does a HIF-1 network reveal characteristics of epithelial-mesenchymal transition in acute promyelocytic leukemia?"
            ]
        },
        {
            "id": "task847-8d7efad5bb0041b9baf7f4dd1d4de45d",
            "input": "Dilated cardiomyopathy (DCM) is a major cause of heart failure that may require heart transplantation. Approximately one third of DCM cases are familial. Next-generation DNA sequencing of large panels of candidate genes (ie, targeted sequencing) or of the whole exome can rapidly and economically identify pathogenic mutations in familial DCM.', 'We recruited 64 individuals from 26 DCM families followed at the Montreal Heart Institute Cardiovascular Genetic Center and sequenced the whole exome of 44 patients and 2 controls. Both affected and unaffected family members underwent genotyping for segregation analysis.', 'We found 2 truncating mutations in BAG3 in 4 DCM families (15%) and confirmed segregation with disease status by linkage (log of the odds [LOD] score = 3.8). BAG3 nonsense mutations conferred a worse prognosis as evidenced by a younger age of clinical onset (37 vs 48 years for carriers and noncarriers respectively; P = 0.037). We also found truncating mutations in TTN in 5 families (19%). Finally, we identified potential pathogenic mutations for 9 DCM families in 6 candidate genes (DSP, LMNA, MYH7, MYPN, RBM20, and TNNT2). We still need to confirm several of these mutations by segregation analysis.",
            "output": [
                "Are nonsense mutations in BAG3 associated with early-onset dilated cardiomyopathy in French Canadians?"
            ]
        },
        {
            "id": "task847-20a89a5123d1435ba2927265450a484c",
            "input": "Previous studies have reported on prognostic factors for castration-resistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC.', 'To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset.', 'The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009.', 'We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time.",
            "output": [
                "Are bone-related Parameters the Main Prognostic Factors for Overall Survival in Men with Bone Metastases from Castration-resistant Prostate Cancer?"
            ]
        },
        {
            "id": "task847-34a7895da76447169dc1d0a4f2f6d8c8",
            "input": "In primary care surveillance systems based on voluntary participation, biased results may arise from the lack of representativeness of the monitored population and uncertainty regarding the population denominator, especially in health systems where patient registration is not required.', 'Based on the observation of a positive association between number of cases reported and number of consultations by the participating general practitioners (GPs), we define several weighted incidence estimators using external information on consultation volume in GPs. These estimators are applied to data reported in a French primary care surveillance system based on voluntary GPs (the Sentinelles network) for comparison.', 'Depending on hypotheses for weight computations, relative changes in weekly national-level incidence estimates up to 3% for influenza, 6% for diarrhea, and 11% for varicella were observed. The use of consultation-weighted estimates led to bias reduction in the estimates. At the regional level (NUTS2 level - Nomenclature of Statistical Territorial Units Level 2), relative changes were even larger between incidence estimates, with changes between -40% and +55%. Using bias-reduced weights decreased variation in incidence between regions and increased spatial autocorrelation.",
            "output": [
                "Does improving disease incidence estimate in primary care surveillance systems?"
            ]
        },
        {
            "id": "task847-e188fb0a32fe491299cb5934cc4380d5",
            "input": "Oxidative stress is one of the mechanisms underlying pathogenesis in neurodegenerative diseases such as Alzheimer's disease. Generally, oxidative stress represents cell toxicity; however, we recently found that oxidative stress promotes the expression of growth factor progranulin (PGRN) in HT22 murine hippocampus cells, thereby protecting the HT22 cells. In this study, we attempted to clarify whether a similar system exists in the other neuronal cell model, rat pheochromocytoma (PC12) cells.\", 'After confirming that high concentrations of hydrogen peroxide (H2O2; 100-250\\xa0\u03bcM) initiate PC12 cell death, we analyzed growth factor expressional changes after H2O2 treatment. We found, intriguingly, that gene expression of brain-derived neurotrophic factor (BDNF), but not PGRN was significantly induced by H2O2. Although little expression of the high affinity BDNF receptor tropomyosin-related kinase TrkB was observed in PC12 cells, expression of low affinity neurotrophin receptor, p75NTR, was clearly observed. This BDNF signaling appeared to contribute to PC12 cell protection, since PC12 cell death was significantly attenuated by BDNF treatment.",
            "output": [
                "Do subtoxic levels of hydrogen peroxide induce brain-derived neurotrophic factor expression to protect PC12 cells?"
            ]
        },
        {
            "id": "task847-f1feeea193f64773aa96efd5ccf19bd1",
            "input": "DUF642 proteins constitute a highly conserved family of proteins that are associated with the cell wall and are specific to spermatophytes. Transcriptome studies have suggested that members of this family are involved in seed development and germination processes. Previous in vitro studies have revealed that At4g32460- and At5g11420-encoded proteins interact with the catalytic domain of pectin methyl esterase 3 (AtPME3, which is encoded by At3g14310). PMEs play an important role in plant development, including seed germination. The aim of this study was to evaluate the function of the DUF642 gene At4g32460 during seed germination and plant development and to determine its relation to PME activity regulation.', 'Our results indicated that the DUF642 proteins encoded by At4g32460 and At5g11420 could be positive regulators of PME activity during several developmental processes. Transgenic lines overexpressing these proteins showed increased PME activity during seed germination, and improved seed germination performance. In plants expressing At4g32460 antisense RNA, PME activity was decreased in the leaves, and the siliques were very short and contained no seeds. This phenotype was also present in the SALK_142260 and SALK_054867 lines for At4g32460.",
            "output": [
                "Is bIIDXI , the At4g32460 DUF642 gene , involved in pectin methyl esterase regulation during Arabidopsis thaliana seed germination and plant development?"
            ]
        },
        {
            "id": "task847-3e022ee2665547ebb1ea94def0639a9e",
            "input": "Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N\\xa0=\\xa0398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility.",
            "output": [
                "Is persistent arm pain distinct from persistent breast pain following breast cancer surgery?"
            ]
        },
        {
            "id": "task847-00ebdcc33720493997e3bb3293137307",
            "input": "Interindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N\\xa0=\\xa0398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction.",
            "output": [
                "Is persistent breast pain following breast cancer surgery associated with persistent sensory changes , pain interference , and functional impairments?"
            ]
        },
        {
            "id": "task847-d1cab9a3aa0c4de7b66c4c83e24d910d",
            "input": "Foxhead box M1 (FOXM1) expression has been shown to be linked with human papillomavirus (HPV) 16/18-infected cervical cancer. However, the mechanism underlying the induction of FOXM1 in HPV 16/18-infected cancers remains elusive.', 'The mechanistic actions of FOXM1 induced by the E6/NKX2-1 axis in tumor aggressiveness were elucidated in cellular and animal models. The prognostic value of FOXM1 for overall survival (OS) and relapse-free survival (RFS) in HPV-positive oral and lung cancers was assessed using Kaplan-Meier and Cox regression models.', 'Herein, FOXM1 expression is upregulated by E6-mediated NKX2-1 in HPV-positive cervical, oral, and lung cancer cells. Induction of FOXM1 by E6 through the MZF1/NKX2-1 axis is responsible for HPV-mediated soft agar growth, invasiveness, and stemness through activating Wnt/\u03b2-catenin signaling pathway. In a nude mice model, metastatic lung tumor nodules in HPV 18 E6-positive GNM or HPV 16 E6-positive TL-1-injected nude mice were markedly decreased in both cell types with E6 knockdown, FOXM1 knockdown, or treatment with FOXM1 inhibitor (thiostrepton). Among the four subgroup patients, the worst FOXM1 prognostic value for OS and RFS was observed in HPV 16/18-positive patients with tumors with high-expressing FOXM1.",
            "output": [
                "Does up-regulation of FOXM1 by E6 oncoprotein through the MZF1/NKX2-1 axis is require for human papillomavirus-associated tumorigenesis?"
            ]
        },
        {
            "id": "task847-c8a74c134579454ab99c1fbd1cfa38b4",
            "input": "To compare endocrine profiles and IVF outcomes after using GnRH agonists (GnRHa) to trigger final oocyte maturation in women with polycystic ovary syndrome (PCOS) with other hyper-responders.', 'Retrospective cohort study.', 'Academic center.', 'Forty women with PCOS and 74 hyper-responders without PCOS.', 'GnRHa trigger.', 'Number of oocytes.', 'Serum E2, LH, and P levels on the day of GnRHa trigger and the day after trigger did not differ significantly between groups. There were no significant differences in total number of oocytes or percent mature oocytes obtained between groups after controlling for age, antral follicle count, and total days of stimulation. The overall rate of no retrieval of oocytes after trigger was low (2.6%). Fertilization, implantation, clinical pregnancy, and live-birth rates were similar in the two groups. No patients developed ovarian hyperstimulation syndrome (OHSS).",
            "output": [
                "Is use of gonadotropin-releasing hormone agonist trigger during in vitro fertilization associated with similar endocrine profiles and oocyte measures in women with and without polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-a4c86b4d6b9a40c78c2fd83fb18668a4",
            "input": "We evaluated the current role of minimally invasive surgery (MIS) in children with small bowel obstruction (SBO) at our institution.', 'A retrospective review of patients undergoing MIS for acute SBO was performed from 2008 to 2013. The study population was compared with a historical control including patients from 2001 to 2008.', 'There were 71 patients who met inclusion criteria; 35 were male, and 36 were female. Sixty-two children underwent laparoscopy for their first episode of SBO, and 12 underwent laparoscopy for recurrent SBO, accounting for 74 episodes of SBO managed with MIS. The most common etiology of SBO was adhesions (n=40). Laparoscopy and laparoscopic-assisted procedures were associated with shorter nasogastric tube decompression (1.4\u00b12 days [P<.001] and 1.5\u00b12.7 days [P=.002], respectively) and time to regular diet (3.9\u00b14 days [P=.002] and 4.6\u00b12.8 days [P=.024], respectively) compared with those converted to laparotomy (5.1\u00b14.9 days of nasogastric tube decompressions and 8\u00b14.7 days to regular diet). There was no difference in postoperative morbidity comparing laparoscopy (11%), laparoscopic-assisted (5%), and laparoscopic converted to open procedures (18%) (P=.48).",
            "output": [
                "Do laparoscopy for small bowel obstruction in children -- an update?"
            ]
        },
        {
            "id": "task847-5e456c5a6bd2435ab12e914c8d72a35d",
            "input": "To study the value of the cervical length (CL) measurement at 11-14 weeks in predicting second trimester miscarriage occurring at 16-24 weeks.', 'Prospective study in routine obstetric population using transvaginal ultrasound examination to measure the length of the endocervical canal at 11-14 weeks.', 'The study group consisted of 2836 singleton pregnancies. Eleven (0.0038%) women miscarried between 16 and 24 weeks whereas 2825 delivered after 34 weeks. CL was significantly shorter (Mann-Whitney U test, p\\u2009=\\u20090.001), in women that had a second trimester miscarriage in comparison to those who delivered after 34 weeks (median CL 28\\u2009mm versus 32\\u2009mm, respectively). First trimester CL was predictive of a late miscarriage (OR\\u2009=\\u20090.7093304, R(2\\u2009)=\\u20090.1211, AUC\\u2009=\\u20090.7838, p\\u2009<\\u20090.001). The detection rate was 63.64% for 20% screen positive rate.",
            "output": [
                "Is first trimester cervical length associated with mid-trimester loss?"
            ]
        },
        {
            "id": "task847-6d99bb0892ab4d329f83b226354f52f8",
            "input": "Epigenetic modifications play an important role in the regulation of gene transcription and cellular function. Here, we examined if pro-inflammatory factors present in the inflamed joint of patients with rheumatoid arthritis (RA) could regulate histone deacetylase (HDAC) expression and function in fibroblast-like synoviocytes (FLS).', 'Protein acetylation in synovial tissue was assessed by immunohistochemistry. The mRNA levels of HDAC family members and inflammatory mediators in the synovial tissue and the changes in HDAC expression in RA FLS were measured by quantitative (q) PCR. FLS were either transfected with HDAC5 siRNA or transduced with adenoviral vector encoding wild-type HDAC5 and the effects of HDAC5 manipulation were examined by qPCR arrays, ELISA and ELISA-based assays.', 'Synovial class I HDAC expression was associated with local expression of tumour necrosis factor (TNF) and matrix metalloproteinase-1, while class IIa HDAC5 expression was inversely associated with parameters of disease activity (erythrocyte sedimentation rate, C-reactive protein, Disease Activity Score in 28 Joints). Interleukin (IL)-1\u03b2 or TNF stimulation selectively suppressed HDAC5 expression in RA FLS, which was sufficient and required for optimal IFNB, CXCL9, CXCL10 and CXCL11 induction by IL-1\u03b2, associated with increased nuclear accumulation of the transcription factor, interferon regulatory factor 1(IRF1).",
            "output": [
                "Do inflammatory cytokines epigenetically regulate rheumatoid arthritis fibroblast-like synoviocyte activation by suppressing HDAC5 expression?"
            ]
        },
        {
            "id": "task847-77a99f1d8b044c08ad0e09300dbceac6",
            "input": "Serum \u03b1-hydroxybutyrate (\u03b1-HB) is elevated in insulin resistance and diabetes. We tested the hypothesis that the \u03b1-HB level predicts abnormal 1\\u2005h glucose levels and \u03b2-cell dysfunction inferred from plasma insulin kinetics during a 75\\u2005g oral glucose tolerance test (OGTT).', 'This cross-sectional study included 217 patients at increased risk for diabetes. 75\\u2005g OGTTs were performed with multiple postload glucose and insulin measurements over a 30-120\\u2005min period. OGTT responses were analyzed by repeated measures analysis of variance (ANOVA). Multivariable logistic regression was used to predict 1\\u2005h glucose \u2265155\\u2005mg/dL with \u03b1-HB added to traditional risk factors.', 'Mean\u00b1SD age was 51\u00b115\\u2005years (44% male, 25% with impaired glucose tolerance). Fasting glucose and insulin levels, but not age or body mass index (BMI), were significantly higher in the second/third \u03b1-HB tertiles (>3.9\\u2005\u00b5g/mL) than in the first tertile. Patients in the second/third \u03b1-HB tertiles exhibited a higher glucose area under the receiver operating characteristics curve (AUC) and reduced initial slope of insulin response during OGTT. The AUC for predicting 1\\u2005h glucose \u2265155\\u2005mg/dL was 0.82 for a base model that included age, gender, BMI, fasting glucose, glycated hemoglobin (HbA1c), and insulin, and increased to 0.86 with \u03b1-HB added (p=0.015), with a net reclassification index of 52% (p<0.0001).",
            "output": [
                "Does serum \u03b1-hydroxybutyrate ( \u03b1-HB ) predict elevated 1 h glucose levels and early-phase \u03b2-cell dysfunction during OGTT?"
            ]
        },
        {
            "id": "task847-a8ab83a988de4a3cae058735aefc3518",
            "input": "Poor glycemic control early in the course of type 1 diabetes mellitus (T1DM) increases the risk for microvascular complications. However, predictors of deteriorating control after diagnosis have not been described, making it difficult to identify high-risk patients and proactively provide aggressive interventions.', 'We examined whether diagnostic age, gender, and race were associated with deteriorating glycemic control during the first 5\\u2005years after diagnosis.', '2218 pediatric patients with T1DM.', 'We conducted a longitudinal cohort study of pediatric patients with T1DM from the Midwest USA, 1993-2009, evaluating within-patient glycated hemoglobin (HbA1c) trajectories constructed from all available HbA1c values within 5\\u2005years of diagnosis.', '52.6% of patients were male; 86.1% were non-Hispanic Caucasian. The mean diagnostic age was 9.0\u00b14.1\\u2005years. The mean number of HbA1c values/year/participant was 2.4\u00b10.9. HbA1c trajectories differed markedly across age groups, with older patients experiencing greater deterioration than their younger counterparts (p<0.001). HbA1c trajectories, stratified by age, varied markedly by race (p for race\u00d7diagnostic age <0.001). Non-Hispanic African-American patients experienced higher initial HbA1c (8.7% vs 7.6% (71.6 vs 59.6\\u2005mmol/mol); p<0.001), and greater deterioration in HbA1c than non-Hispanic Caucasian patients across diagnostic ages (rise of 2.04% vs 0.99% per year (22.3 vs 10.8\\u2005mmol/mol/year); p<0.0001).",
            "output": [
                "Does age at diagnosis predict deterioration in glycaemic control among children and adolescents with type 1 diabetes?"
            ]
        },
        {
            "id": "task847-e253f032ee19457d9d1172880657a728",
            "input": "Although Alzheimer's disease (AD) is associated with early death, its life expectancy differs greatly between patients. A better understanding of this heterogeneity may reveal important disease mechanisms underlying the malignancy of AD. The aim of this study was to examine the relation between AD pathologies and early death in AD caused by dementia.\", 'At a memory clinic, 247 referred consecutive patients with AD were monitored during 12.6\\u2009\u00b1\\u20091.6 years. Multivariate Cox regression analyses were performed with baseline measures of amyloid beta (A\u03b2) pathology (APOE genotype, cerebrospinal fluid (CSF) A\u03b242) tau pathology (CSF phosphorylated tau and total tau), cerebrovascular pathology (white-matter lesions and CSF/serum albumin ratio), neuroinflammatory pathology (CSF soluble vascular cell adhesion molecule-1, sVCAM-1), frontal, temporal, and central brain atrophies, global cognition, sex, and age. Comorbidities and medications also were analyzed. All continuous variables were transformed to z scores to compare hazard ratios (HRs) and 95% confidence intervals (CIs).', 'At follow-up, 89% of the patients had died. The mean survival time was 6.4\\u2009\u00b1\\u20093.0 years. The AD pathology that independently predicted an early death caused by dementia was cerebral inflammation (sVCAM-1; HR, 1.32; 95% CI, 1.07-1.64). Other independent predictors were lower global cognition (HR, 0.51; 95% CI, 0.43-0.61), frontal atrophy (HR, 1.38; 95% CI, 1.12-1.70), and medial temporal atrophy (HR, 1.23; 95% CI, 1.02-1.49). When examining death caused by dementia and related causes (vascular diseases and infections), age (HR, 1.23; 95% CI, 1.04-1.46) and cerebrovascular pathology (white-matter lesions: HR, 1.17; 95% CI, 1.01-1.36; and CSF/serum albumin ratio: HR, 1.16; 95% CI, 1.001-1.34) were also significant risk factors in addition to the previous variables. No comorbidity or medication was significant in the specific-cause models.",
            "output": [
                "Is cerebral inflammation an underlying mechanism of early death in Alzheimer 's disease : a 13-year cause-specific multivariate mortality study?"
            ]
        },
        {
            "id": "task847-cebe5376ce074202b0a597fe052f050f",
            "input": "Mitochondria are the cell's powerhouse when organisms are grown in the presence of oxygen. They are also the source of reactive oxygen species that cause damage to the biochemical components of the cell and lead to cellular ageing and death. Under winemaking conditions, Saccharomyces yeasts exclusively have a fermentative metabolism due to the high sugar content of grape must. However, their production as an active dry yeast (ADY) form required aerobic propagation and a dehydration process. In these industrial steps, oxidative stress is particularly harmful for the cell. In this work, we analysed the impact of the mitochondrial genome on oxidative stress response, longevity and dehydration tolerance using the synthetic interspecific hybrids obtained between two S. cerevisiae and S. uvarum strains. The isogenic nature of nuclear DNA of such hybrids allowed us to analyse the impact of mitochondrial DNA for fermentative and oxidative stress conditions. Under grape must conditions, the inheritance of mitochondrial DNA poorly impacted the fermentative performance of interspecific hybrids, unlike the hybrids with S. cerevisiae mitochondrial inheritance, which displayed increased tolerance to oxidative stress and dehydration, and showed an extended chronological longevity when cells were grown with aeration.",
            "output": [
                "Is mitochondria inheritance a key factor for tolerance to dehydration in wine yeast production?"
            ]
        },
        {
            "id": "task847-5a7f3c7106a84fa2b2d87d05c042b7a8",
            "input": "To determine the relationship between preoperative catecholamine levels and intraoperative peak plasma lactate levels in patients who underwent adrenalectomy for pheochromocytoma.', 'Retrospective observational study.', 'Operating room in one university hospital.', 'The records of 27 ASA physical status 1 and 2 patients who underwent adrenalectomy for pheochromocytoma were studied. Preoperative catecholamine levels and intraoperative plasma lactate levels were recorded.', \"Twenty cases had high lactate levels (>2 mmol/L). Preoperative urine epinephrine levels and urine metanephrine levels showed a moderate correlation with intraoperative peak plasma lactate levels (rs = 0.475 and rs = 0.499, respectively; Spearman's rank correlation test). Receiver operating characteristic (ROC) curve analysis for preoperative urine epinephrine levels showed good performance for prediction of high lactate levels [>2 mmol/L, area under the curve (AUC) =0.800], whereas ROC for preoperative urine norepinephrine levels showed no predictive performance for high lactate levels.",
            "output": [
                "Does catecholamine release induce elevation in plasma lactate levels in patients undergoing adrenalectomy for pheochromocytoma?"
            ]
        },
        {
            "id": "task847-1ae722fe4f8c4b16abca8beba114d46e",
            "input": "Development of perfusion imaging as a biomarker requires more robust methodologies for quantification of tumor physiology that allow assessment of volumetric tumor heterogeneity over time. This study proposes a parametric method for automatically analyzing perfused tissue from volumetric dynamic contrast-enhanced (DCE) computed tomography (CT) scans and assesses whether this 4-dimensional (4D) DCE approach is more robust and accurate than conventional, region-of-interest (ROI)-based CT methods in quantifying tumor perfusion with preliminary evaluation in metastatic brain cancer.', 'Functional parameter reproducibility and analysis of sensitivity to imaging resolution and arterial input function were evaluated in image sets acquired from a 320-slice CT with a controlled flow phantom and patients with brain metastases, whose treatments were planned for stereotactic radiation surgery and who consented to a research ethics board-approved prospective imaging biomarker study. A voxel-based temporal dynamic analysis (TDA) methodology was used at baseline, at day 7, and at day 20 after treatment. The ability to detect changes in kinetic parameter maps in clinical data sets was investigated for both 4D TDA and conventional 2D ROI-based analysis methods.', 'A total of 7 brain metastases in 3 patients were evaluated over the 3 time points. The 4D TDA method showed improved spatial efficacy and accuracy of perfusion parameters compared to ROI-based DCE analysis (P<.005), with a reproducibility error of less than 2% when tested with DCE phantom data. Clinically, changes in transfer constant from the blood plasma into the extracellular extravascular space (Ktrans) were seen when using TDA, with substantially smaller errors than the 2D method on both day 7 post radiation surgery (\u00b113%; P<.05) and by day 20 (\u00b112%; P<.04). Standard methods showed a decrease in Ktrans but with large uncertainty (111.6 \u00b1 150.5) %.",
            "output": [
                "Does automated voxel-based analysis of volumetric dynamic contrast-enhanced CT data improve measurement of serial changes in tumor vascular biomarkers?"
            ]
        },
        {
            "id": "task847-51f6aed7b2d24314b7844db5c755059c",
            "input": "Lack of insurance is associated with suboptimal receipt of diabetes preventive care. One known reason for this is an access barrier to obtaining healthcare visits; however, little is known about whether insurance status is associated with differential rates of receipt of diabetes care during visits.', 'To examine the association between health insurance and receipt of diabetes preventive care during an office visit.', 'This retrospective cohort study used electronic health record and Medicaid data from 38 Oregon community health centers. Logistic regression was used to test the association between insurance and receipt of four diabetes services during an office visit among patients who were continuously uninsured (n=1,117); continuously insured (n=1,466); and discontinuously insured (n=336) in 2006-2007. Generalized estimating equations were used to account for within-patient correlation. Data were analyzed in 2013.', 'Overall, continuously uninsured patients had lower odds of receiving services at visits when due, compared to those who were continuously insured (AOR=0.73, 95% CI=0.66, 0.80). Among the discontinuously insured, being uninsured at a visit was associated with lower odds of receipt of services due at that visit (AOR=0.77, 95% CI=0.64, 0.92) than being insured at a visit.",
            "output": [
                "Does receipt of diabetes preventive services differ by insurance status at visit?"
            ]
        },
        {
            "id": "task847-a021687ddbc542a7a1898277d24248ef",
            "input": "The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations.', 'Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 \u03b3 rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above.', 'HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses \u22640.4 Gy than for doses >0.5 Gy.",
            "output": [
                "Is cytogenetic low-dose hyperradiosensitivity observed in human peripheral blood lymphocytes?"
            ]
        },
        {
            "id": "task847-d92c1a8a48a54291828ebc429476afba",
            "input": "This study evaluated two surgical procedures, total splenectomy and spleen-preserving surgery, for the treatment of spleen cystic echinococcosis (CE).', 'A total of 21 patients who underwent surgery for removal of spleen CE were evaluated retrospectively. Patients were divided into two groups, those who received a total splenectomy (n=7) and those who underwent spleen-preserving surgery (n=14).', 'Total splenectomy surgery took 127.1\u00b111.1min and spleen-preserving surgery took 104.3\u00b125.3min (p<0.05). The length of hospital stay was the same for both patient groups (10.6 days on average). No patient suffered from recurrence during follow-up and all of the patients made a good recovery. No patient developed post-splenectomy sepsis or serious infectious complications. No patient suffered recurrence.",
            "output": [
                "Is spleen-preserving surgery effective for the treatment of spleen cystic echinococcosis?"
            ]
        },
        {
            "id": "task847-aac73e51286145d69b27319459044fe5",
            "input": "Diabetic patients commonly suffer from disturbances in production and clearance of plasma lipoproteins, known as diabetic dyslipidemia, resulting in an increased risk of coronary heart disease. The study aimed to examine the cause of hypobetalipoproteinemia in two patients with type 1 diabetes.', 'The Diabetes Control and Complications Trial (DCCT) is a study demonstrating that intensive blood glucose control delays the onset and progression of type 1 diabetes complications. Hypobetalipoproteinemia was present in two DCCT subjects, IDs 1427 and 1078, whose LDL-C levels were 36 and 28 mg/dL, respectively, and triglyceride levels were 20 and 28 mg/dL, respectively. We performed exome sequencing on genomic DNA from the two patients with hypobetalipoproteinemia.', 'The subjects 1427 and 1078 had heterozygous loss-of-function mutations in the gene apolipoprotein B (ApoB), and these mutations resulted in premature stop codons at amino acid 1333 (ApoB-29) and 3680 (ApoB-81), respectively. Indeed, the plasma ApoB level of subject 1427 (19 mg/dL) was the lowest and that of subject 1078 (26 mg/dL) was the second to the lowest among all the 1,441 DCCT participants. Sequencing genomic DNA of family members showed that probands 1427 and 1078 inherited the mutations from the father and the mother, respectively.",
            "output": [
                "Does exome sequencing identify novel ApoB loss-of-function mutations causing hypobetalipoproteinemia in type 1 diabetes?"
            ]
        },
        {
            "id": "task847-91f2ab57569b4ae0a89d79d72baa1ddd",
            "input": "Correlation between tumor volume and hormone levels in individual patients would permit calculation of the fraction of tumor removed by surgery, by measuring postoperative hormone levels. The goals of this study were to examine the relationship between tumor volume, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) levels, and to assess the correlation between percent tumor removal and the reduction in plasma GH and IGF-1 in patients with acromegaly.', 'The 3D region of interest-based volumetric method was used to measure tumor volume via MRI before and after surgery in 11 patients with GH-secreting adenomas. The volume of residual tumor as a fraction of preoperative tumor volume was correlated with GH levels before and after surgery. Examination of this potential correlation required selection of patients with acromegaly who 1) had incomplete tumor removal, 2) had precise measurements of initial and residual tumor, and 3) were not on medical therapy.', 'Densely granulated tumors produced more peripheral GH per mass of tumor than sparsely granulated tumors (p = 0.04). There was a correlation between GH and IGF-1 levels (p = 0.001). Although there was no close correlation between tumor size and peripheral GH levels, after normalizing each tumor to its own plasma GH level and tumor volume, a comparison of percent tumor resection with percent drop in plasma GH yielded a high correlation coefficient (p = 0.006).",
            "output": [
                "Does percent reduction of growth hormone levels correlate closely with percent resected tumor volume in acromegaly?"
            ]
        },
        {
            "id": "task847-afe4b55600b34f44919568d0bbe441dd",
            "input": "Glioma differentiation therapy is a novel strategy that has been used to induce glioma cells to differentiate into glia-like cells. Although some advances in experimental methods for exploring the molecular mechanisms involved in differentiation therapy have been made, a model-based comprehensive analysis is still needed to understand these differentiation mechanisms and improve the effects of anti-cancer therapeutics. This type of analysis becomes necessary in stochastic cases for two main reasons: stochastic noise inherently exists in signal transduction and phenotypic regulation during targeted therapy and chemotherapy, and the relationship between this noise and drug efficacy in differentiation therapy is largely unknown.', 'In this study, we developed both an additive noise model and a Chemical-Langenvin-Equation model for the signaling pathways involved in glioma differentiation therapy to investigate the functional role of noise in the drug response. Our model analysis revealed an ultrasensitive mechanism of cyclin D1 degradation that controls the glioma differentiation induced by the cAMP inducer cholera toxin (CT). The role of cyclin D1 degradation in human glioblastoma cell differentiation was then experimentally verified. Our stochastic simulation demonstrated that noise not only renders some glioma cells insensitive to cyclin D1 degradation during drug treatment but also induce heterogeneous differentiation responses among individual glioma cells by modulating the ultrasensitive response of cyclin D1. As such, the noise can reduce the differentiation efficiency in drug-treated glioma cells, which was verified by the decreased evolution of differentiation potential, which quantified the impact of noise on the dynamics of the drug-treated glioma cell population.",
            "output": [
                "Does stochastic modeling suggest that noise reduces differentiation efficiency by inducing a heterogeneous drug response in glioma differentiation therapy?"
            ]
        },
        {
            "id": "task847-1db59c43bd9d4ae99b5e9aff00a517c2",
            "input": "Active engagement in education improves learning outcomes. To enhance active participation in seminars, a student-centered course design was implemented and evaluated in terms of self-reported preparation, student motivation and exam scores. We hypothesized that small group learning with intensive peer interaction, using buzz-groups followed by plenary discussion, would motivate students to prepare seminar assignments at home and to actively engage in the seminars. Active engagement involved discussion of the preparatory assignments until consensus was reached.', \"In total seven seminars were scheduled in a 10-week physiology course of an undergraduate Biomedical Sciences program. After each seminar, students were asked to fill out their perceptions of preparation and quality of the seminar (deepening of knowledge and confidence in answers) on a five-point scale using electronic questionnaires. Student motives were first collected using open questions. In the final questionnaire students were asked to indicate on a five-point scale how each motive was perceived. Students overall explanations why they had learned from seminars were collected via open questions in the final questionnaire. One hundred and twenty-four students of the cohort from November 2012 to February 2013 (82.6\\xa0%) voluntarily participated. Students' motives to prepare and attend seminars were analyzed by inspection of descriptive statistics. Linear regression analysis was conducted to relate student preparation to the quality of seminars, seminar attendance to exam scores, and exam scores to the quality of seminars. Answers to open questions were deductively clustered.\", \"Studying the material, training for exams and comparing answers with peers motivated students to prepare the seminars. Students were motivated to participate actively because they wanted to keep track of correct answers themselves, to better understand the content and to be able to present their findings in plenary discussions. Perceived preparation of peers was positively associated with the perceived quality of seminars. Also, seminar attendance was positively associated with exam scores. Students' overall explanations suggest that discussing with peers and applying knowledge in pathophysiology cases underlies this association.",
            "output": [
                "Is peer-instructed seminar attendance associated with improved preparation , deeper learning and higher exam scores : a survey study?"
            ]
        },
        {
            "id": "task847-6d9740f65d6246a88fe947c1fc6de41e",
            "input": "An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome.', 'Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48\\xa0h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24\\xa0h Sequential Organ Failure Assessment (SOFA) score\\u2009\u2265\\u200912. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed.', 'Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48\\xa0% (133 of 276) to 1\\xa0year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48\\xa0h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24\\xa0h SOFA and cardiovascular SOFA score (p\\u2009<\\u20090.0001) and in those who developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6 [9.1-26.2] ng/mL, p\\u2009<\\u20090.0001; AUC\\u2009=\\u20090.70\\u2009\u00b1\\u20090.04, p\\u2009=\\u20090.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL) compared to those who survived (13.5 [9.1-25.5] ng/mL, p\\u2009<\\u20090.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p\\u2009<\\u20090.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74\\u2009\u00b1\\u20090.04 (p\\u2009<\\u20090.0001) and were independently associated with ICU death (OR [95 %CI] 1.607 [1.076-2.399], p\\u2009=\\u20090.020), but not with unfavorable 12-month neurological outcome (OR [95 %CI] 1.154 [0.834-1.596], p\\u2009=\\u20090.387).",
            "output": [
                "Is elevated plasma heparin-binding protein associated with early death after resuscitation from cardiac arrest?"
            ]
        },
        {
            "id": "task847-c85e8c774de243b4af609a0b9feee39b",
            "input": "Patient-oncologist alliance and psychosocial well-being have strong associations with adherence to cancer management. For patients with cancer of unknown primary (CUP), adherence is crucial to treatment or occult primary screening plans. There has been no study investigating the relationship between alliance, psychosocial factors, and adherence in such patients or in Chinese sociocultural settings.', 'The measures of alliance, psychosocial well-being, and adherence willingness were administered to patients with CUP, with a mean age of 58.33 \u00b1 11.24 years. Multiple linear regression models were applied to investigate the independent relationship between alliance and adherence by controlling for socioeconomic and psychosocial confounders.', 'Alliance was found to be independently and positively associated with greater adherence willingness and adherence to treatment and follow-up screening after controlling for significant confounders, including medical conditions, psychosocial well-being variables, and socioeconomic factors.",
            "output": [
                "Do patient-oncologist alliance and psychosocial well-being in Chinese society strongly affect cancer management adherence with cancer of unknown primary?"
            ]
        },
        {
            "id": "task847-a8f41cd3c4d7490dac071b188970a718",
            "input": "Transcriptome analysis may provide means to investigate the underlying genetic causes of shared and divergent phenotypes in different populations and help to identify potential targets of adaptive evolution. Applying RNA sequencing to whole male Drosophila melanogaster from the ancestral tropical African environment and a very recently colonized cold-temperate European environment at both standard laboratory conditions and following a cold shock, we seek to uncover the transcriptional basis of cold adaptation.', 'In both the ancestral and the derived populations, the predominant characteristic of the cold shock response is the swift and massive upregulation of heat shock proteins and other chaperones. Although we find ~25\\xa0% of the genome to be differentially expressed following a cold shock, only relatively few genes (n\\u2009=\\u200916) are up- or down-regulated in a population-specific way. Intriguingly, 14 of these 16 genes show a greater degree of differential expression in the African population. Likewise, there is an excess of genes with particularly strong cold-induced changes in expression in Africa on a genome-wide scale.",
            "output": [
                "Is canalization of gene expression a major signature of regulatory cold adaptation in temperate Drosophila melanogaster?"
            ]
        },
        {
            "id": "task847-2f5a18ee7afb4a8a8660e79a850a70d4",
            "input": "High enterolactone levels may have health benefits in relation to risk of noncommunicable diseases. Enterolactone is produced by the colonic microbiota after intake of lignans and treatment with antimicrobials may result in altered enterolactone production. This study investigates the association between antibiotic use and enterolactone concentration.', 'Using LC-MS/MS, enterolactone concentrations were quantified in plasma samples from 2237 participants from the Diet, Cancer and Health cohort. The participants were healthy at enrollment, but were later diagnosed with cancer. At enrollment, participants had blood drawn and completed a food frequency questionnaire and lifestyle questionnaire. Antibiotic use was assessed as reimbursed antibiotic prescriptions up to 12 months before enrollment. Antibiotic use \u22643 months before enrollment was associated with a 41% (\u0394",
            "output": [
                "Is use of antibiotics associated with lower enterolactone plasma concentration?"
            ]
        },
        {
            "id": "task847-c18341bddcd946108b11a6612e2f21cc",
            "input": "The role of anaplerotic nutrient entry into the Krebs cycle via pyruvate carboxylase has been the subject of increased scrutiny and in particular whether this is dysregulated in cancer. Here, we use a tracer-based NMR analysis involving high-resolution (1)H-(13)C-HSQC spectra to assess site-specific label incorporation into a range of metabolite pools, including malate, aspartate and glutamate in the acute myeloid leukaemia cell line K562. We also determine how this is affected following treatment with the redeployed drug combination of the lipid-regulating drug bezafibrate and medroxyprogesterone (BaP).', 'Using the tracer-based approach, we assessed the contribution of pyruvate carboxylase (PC) vs. pyruvate dehydrogenase (PDH) activity in the derivation of Krebs cycle intermediates. Our data show that PC activity is indeed high in K562 cells. We also demonstrate a branched entry to the Krebs cycle of K562 cells with one branch running counterclockwise using PC-derived oxaloacetate and the other clockwise from the PDH activity. Finally, we show that the PC activity of K562 cells exclusively fuels the ROS-induced decarboxylation of oxaloacetate to malonate in response to BaP treatment; resulting in further Krebs cycle disruption via depletion of oxaloacetate and malonate-mediated inhibition of succinate dehydrogenase (SDH) resulting in a twofold reduction of fumarate.",
            "output": [
                "Is malonate as a ROS product associated with pyruvate carboxylase activity in acute myeloid leukaemia cells?"
            ]
        },
        {
            "id": "task847-b8971149a43347578e2a64ee791283cf",
            "input": "To determine the effect of SLCO1B1 gene polymorphisms (rs11045819, rs4149032 and rs4149033) on rifampicin (RMP) concentrations in adult tuberculosis (TB) patients from south India.', 'We genotyped adult TB patients for three SLCO1B1 gene polymorphisms-rs11045819, rs4149032 and rs4149033-and compared 2-h post-dosing RMP concentrations of the different genotypes for each of the polymorphisms. Plasma RMP was determined using high-performance liquid chromatography. Genotyping was performed using direct sequencing.', 'Among the 256 study patients, minor allele frequencies were respectively 0.01 (A), 0.46 (C) and 0.07 (A) for rs11045819, rs4149032 and rs4149033 polymorphisms; genotype distributions followed Hardy-Weinberg equilibrium. RMP concentrations did not significantly differ between the different genotypes of the three polymorphisms.",
            "output": [
                "Do sLCO1B1 gene polymorphisms influence plasma rifampicin concentrations in a South Indian population?"
            ]
        },
        {
            "id": "task847-9050c110981c401cbf1b273ac4c3a998",
            "input": "Depression is a prevalent comorbidity of chronic respiratory disease (CRD), and may indicate worse clinical outcomes. The relationship between depression and living with chronic hypoxia due to CRD or residence at altitude has received little attention in resource-poor settings.', 'To investigate the association between CRD conditions and depressive symptoms in four settings in Peru.', 'We collected data on CRD and depressive symptoms in adults aged \u2a7e35 years. Depressive symptoms were measured according to the Center for Epidemiologic Studies Depression scale. Multivariable ordinal logistic regression was used to assess the adjusted odds of being in a higher category of depressive symptoms as a function of CRD.', 'We analyzed data from 2953 participants (mean age 55.3 years, 49% male). The prevalence of major depressive symptoms was 19%, with significant variation according to setting. Participants with at least one CRD (OR 1.34, 95%CI 1.06-1.69) and those living at altitude (OR 1.64, 95%CI 1.10-2.43) had an increased adjusted odds of being in a higher category of depressive symptoms.",
            "output": [
                "Are chronic respiratory disease and high altitude associated with depressive symptoms in four diverse settings?"
            ]
        },
        {
            "id": "task847-c38f1d70d1784a479bc16586b7b6cb35",
            "input": "To evaluate the relationship between pro-atherogenic biomarkers and epicardial adipose tissue (EAT) thickness in patients with cardiovascular risk factors.', 'Plasma nitric oxide (NO), soluble intercellular adhesion molecule-1 and malondialdehyde (MDA) levels, EAT thickness, flow-mediated dilation (FMD) and carotid intima media thickness (CIMT) were determined in patients aged >18 years who were referred for echocardiography for heart ischemia or non-ischemic diseases. Cardiovascular risk factors (Framingham score [FS]\\u2009\u2265\\u200920) were weighted.', 'Hypertension, dyslipidaemia and type 2 diabetes mellitus were prevalent (\u226555% of 40 patients). Patients with FS\\u2009\u2265\\u200920 (n\\u2009=\\u200921) showed significantly higher EAT and CIMT values. Globally, MDA, CIMT, age, waist circumference, high-density lipoprotein cholesterol (HDL-C) and FS were associated with EAT thickness. EAT was significantly associated with NO in patients with FS\\u2009\u2265\\u200920. Significant differences in EAT thickness were found between patients stratified by NO value, FMD, age, smoking status, dyslipidaemia, type 2 diabetes mellitus and FS. An EAT-associated atherogenic risk (CIMT\\u2009\u2265\\u20091\\u2009mm) model was statistically significant when MDA and type 2 diabetes mellitus were included.",
            "output": [
                "Are pro-atherogenic mediators and subclinical atherogenesis related to epicardial adipose tissue thickness in patients with cardiovascular risk?"
            ]
        },
        {
            "id": "task847-55791be6dd38423483bf9014b8db275c",
            "input": "Recent research has revealed that classically trained tenors tend to constrict epilaryngeal structures when singing in and above the passaggio (ie, the frequency region where register events typically occur). These constrictions complicate visibility of vocal fold oscillatory patterns with transoral rigid high-speed video endoscopy, thus limiting the current understanding of laryngeal dynamics in the passaggio region of tenors.', 'This investigation analyzed seven professionally trained western classical tenors using high-speed digital imaging (HSDI) at 20,000 frames per second via transnasal flexible endoscopy. The participants produced transitions (a) from modal to falsetto register and (b) from modal to stage voice above the passaggio (SVaP) during ascending pitch glides from A3 (220\\u2009Hz) to A4 (440\\u2009Hz) on vowel /i/. HSDI data were complemented by simultaneous acoustic and electroglottographic recordings.', 'For many subjects both transition types were associated with constrictions of the epilaryngeal structures during the pitch glide. These constrictions appeared to be more distinct for the SVaP than for falsetto. No major irregularities of vocal fold oscillations in the sense of fundamental frequency jumps were observed for either transition type. However, during the transitions, the open quotient derived from the glottal area waveform (OQ",
            "output": [
                "Does oscillatory Characteristics of the Vocal fold Across the Tenor Passaggio?"
            ]
        },
        {
            "id": "task847-568fbe0a5dba43018ab26f1401770436",
            "input": "Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often only marginal methylation changes remains unclear.', 'Comparing genome-wide changes in CpG methylation of three recently reported epidemiological datasets, two obtained on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes evident that the majority of methylation changes (86.7 and 93.3\\xa0%) in whole blood account for changes in granulocytes. Analyzing, in more detail, seven highly significant reported smoking-induced methylation changes at single CpGs in different blood cell types of healthy volunteers (n\\u2009=\\u200932), we confirmatively found a strong cell-type specificity. Two CpGs in GFI1 and F2RL3 were significantly hypomethylated in granulocytes (-11.3\\xa0%, p\\u2009=\\u20090.001; -8.7\\xa0%, p\\u2009=\\u20090.001, respectively) but not in PBMCs of smokers while two CpGs in CPOX and GPR15 were found to be hypomethylated in PBMC (-4.3\\xa0%, p\\u2009=\\u20090.003; -4.2\\xa0%, P\\u2009=\\u20090.009, respectively) and their subtypes of GPR15 non-expressing (-3.2\\xa0%, p\\u2009=\\u20090.027; -2.5\\xa0%, p\\u2009=\\u20090.032, respectively) and smoking-evoked GPR15 expressing T cells (-15.8\\xa0%, p\\u2009<\\u20090.001; -13.8\\xa0%, p\\u2009=\\u20090.018, respectively) but not in granulocytes. In contrast, cg05575921 within AHRR was hypomethylated in every analyzed cell type of smokers, but with a different degree. Both, hypomethylation at cg05575921 in granulocytes (-55.2\\xa0% methylation change in smokers, p\\u2009<\\u20090.001) and the frequency of GPR15+ T cells (9.8-37.1\\xa0% in smokers), possessing a specific hypomethylation at cg19859270, were strongly associated with smoking behavior at individual level and could therefore serve as valuable biomarkers indicating a disturbed homeostasis in smokers. In contrast to the reported long-term persistent methylation changes in adult smokers after cessation, the hypomethylation at cg05575921 in prenatally tobacco smoke-exposed children (n\\u2009=\\u200913) from our LINA cohort was less stable and disappeared already within 2\\xa0years after birth.",
            "output": [
                "Does tobacco smoking differently influence cell types of the innate and adaptive immune system-indications from CpG site methylation?"
            ]
        },
        {
            "id": "task847-14a3e30e8e184c42aa651d6aa574590d",
            "input": "As wearable sensors/devices become increasingly popular to promote physical activity (PA), research is needed to examine how and which components of these devices people use to increase their PA levels.', '(1) To assess usability and level of engagement with the Fitbit One and daily SMS-based prompts in a 6-week PA intervention, and (2) to examine whether use/ level of engagement with specific intervention components were associated with PA change.', 'Data were analyzed from a randomized controlled trial that compared (1) a wearable sensor/ device (Fitbit One) plus SMS-based PA prompts, and (2) Fitbit One only, among overweight/ obese adults (N = 67). We calculated average scores from Likert-type response items that assessed usability and level of engagement with device features (e.g., tracker, website, mobile app, and SMS-based prompts), and assessed whether such factors were associated with change in steps/day (using Actigraph GT3X+).', 'Participants reported the Fitbit One was easy to use and the tracker helped to be more active. Those who used the Fitbit mobile app (36%) vs. those who did not (64%) had an increase in steps at 6-week follow-up, even after adjusting for previous web/app use: +545 steps/ day (",
            "output": [
                "Does mobile and Wearable Device feature that Matter in Promoting Physical Activity?"
            ]
        },
        {
            "id": "task847-f03e91598d1e4effa713b45530419ff3",
            "input": "Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies.', 'Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established. The expression levels of miRNAs previously shown to be involved in the general regulation of stem cell pathways were analyzed by qRT-PCR. The effects of selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated both in vitro and in vivo. We identified a particular miRNA and analyzed its putative target genes in 14 pairs of human EC tumor specimens with surrounding normal tissue by qRT-PCR as well as Wnt pathway associated genes by immunohistochemistry in another 45 EAC tumor samples.', 'MiR-221 was overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue. DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU resistant cells resulted in reduced cell proliferation, increased apoptosis, restored chemosensitivity, and led to inactivation of the Wnt/\u03b2-catenin pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as well as significantly slower xenograft tumor growth in nude mice. RT profiler analysis identified a substantial dysregulation of 4 Wnt/\u03b2-catenin signaling and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44, MYC, and ABCG2.",
            "output": [
                "Does miR-221 mediate Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting of DKK2 Expression?"
            ]
        },
        {
            "id": "task847-3fd3424263134235aead81cf1fe84cf1",
            "input": "Characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, current therapy options are not satisfactory. PKI-587 is a highly potent novel dual inhibitor of PI3K and mTORC1/C2.', 'We assessed the effects of PKI-587 in different GEP-NEN tumor models, including poorly differentiated cell line LCC-18, compared with the established mTORC1 inhibitor everolimus.', 'We treated the cell lines BON, QGP1, KRJ-I and LCC-18 with increasing concentrations of the inhibitor PKI-587, and compared with everolimus and DMSO. We assessed the impact of treatments on viability (WST-1 assay), on apoptotic processes (Caspase 3/7 assay, JC-1) and on cell cycle regulation (flow cytometry). We determined alterations of signaling mediators by phosphor-specific western blot analysis and conducted multiplexed gene expression analysis (nCounter\u00ae technology).', 'In all cell lines, PKI-587 dose-dependently inhibited proliferation whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest, induction of apoptosis and successfully suppressed activity of direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT and PI3K pathway genes after treatment. Treatment dependent and cell line characteristic effects on AKT/RB/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this article.",
            "output": [
                "Is inhibition of mTORs Catalytic Site by PKI-587 a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease?"
            ]
        },
        {
            "id": "task847-899250da09424690b64955f832c43635",
            "input": "Natriuretic peptides and echocardiographic parameters both predict cardiovascular events in patients with CKD. However, it is unknown whether simultaneous assessment of amino-terminal probrain natriuretic peptide (NT-proBNP) and echocardiographic parameters provides complementary or redundant predictive information; in the latter case, one of these two might be dispensable. We aimed to analyze the implications of using NT-proBNP alone, echocardiographic parameters alone, or a combination of both for prediction of adverse cardiovascular outcome.', 'Within the longitudinal Cardiovascular and Renal Outcome in CKD 2-4 Patients-The Fourth Homburg Evaluation Study, we prospectively studied 496 patients with CKD stages G2-G4, in whom we measured NT-proBNP. Left ventricular mass index, left atrial volume index, diastolic left ventricular function, and systolic left ventricular function were assessed echocardiographically. During 4.5\u00b12.0 years of follow-up, the occurrence of (1) decompensated heart failure or all-cause mortality and (2) atherosclerotic events or all-cause mortality was recorded. We assessed the association of NT-proBNP and echocardiographic parameters with outcome (using Cox models) and evaluated the increased discriminative value associated with the addition of echocardiographic parameters and NT-proBNP (using integrated discrimination improvement and net reclassification improvement).', 'During follow-up, 104 patients suffered decompensated heart failure or all-cause mortality, and 127 patents had atherosclerotic events or all-cause mortality. In univariable analyses, NT-proBNP and echocardiographic parameters predicted cardiovascular events. NT-proBNP remained an independent predictor for both end points in multivariate analysis, whereas left ventricular mass index, left atrial volume index, and diastolic left ventricular function did not. The addition of NT-proBNP on top of clinical and various echocardiographic variables was associated with improvements in reclassification for decompensated heart failure or all-cause mortality (integrated discrimination improvement =6.5%-8.3%; net reclassification improvement =23.1%-27.0%; all P\u22640.03). Adding echocardiographic variables on top of clinical variables and NT-proBNP was not associated with significant net reclassification improvement (all P>0.05).",
            "output": [
                "Does nT-proBNP and Echocardiographic Parameters for Prediction of Cardiovascular Outcomes in Patients with CKD stage G2-G4?"
            ]
        },
        {
            "id": "task847-58a856dc90c54a04b633a8e7a02080a4",
            "input": "The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GR\u03b1) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics.', 'Airway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-\u03b1 and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR. Immunohistochemistry and flow cytometry assays were used to assess the expression of the protein phosphatase PP5 in endobronchial biopsies and ASM cells.', 'The production of CCL11 and CCL5 by TNF-\u03b1 was insensitive to both fluticasone and dexamethasone in ASM cells from severe asthmatic compared to that in healthy subjects. Fluticasone-induced GR\u03b1 nuclear translocation, phosphorylation at serine 211 and expression of GC-induced leucine zipper (GILZ) were significantly reduced in ASM cells from severe asthmatics compared to responses in healthy subjects. Levels of PP5 were increased in ASM cells from severe asthmatics and PP5 knockdown using siRNA restored fluticasone repressive action on chemokine production and its ability to induce GR\u03b1 nuclear translocation and GRE-dependent GILZ expression. In vivo PP5 expression was also increased in the ASM bundles in endobronchial biopsies in severe asthmatics.",
            "output": [
                "Does protein phosphatase 5 mediate corticosteroid insensitivity in airway smooth muscle in patients with severe asthma?"
            ]
        },
        {
            "id": "task847-fce313ae44a74607849fd9ffb9d7a176",
            "input": "The serrated pathway is a distinct pathway of colorectal carcinogenesis that has been implicated in development of a substantial proportion of interval colorectal cancers. The fecal immunochemical test (FIT) detects early neoplasms with a higher level of sensitivity than the guaiac test. We investigated the sensitivity of the FIT in detection of sessile serrated adenomas/polyps (SSA/Ps).', 'We performed a prospective study of 6198 asymptomatic subjects (mean age, 59.0 \u00b1 7.0 years) who received concurrent screening colonoscopies and FITs at the Health Management Center of National Taiwan University Hospital from August 2010 through November 2014. The sensitivity of FIT for conventional adenoma, advanced adenoma, and SSA/P at different cutoffs was calculated, and results were compared by using multivariate analysis adjusted for potential confounders.', 'Prevalence values of SSA/P, adenoma, and advanced adenoma were 1.4%, 20.2%, and 5.5%, respectively. At cutoffs of 10, 15, and 20 \u03bcg hemoglobin/g feces, the FIT detected all SSA/Ps with 12.3%, 6.2%, and 6.2% sensitivity, large SSA/Ps with 18.4%, 10.5%, and 10.5% sensitivity, and advanced adenomas with 32.4%, 24.5%, and 20.9% sensitivity, respectively. Multivariate analysis revealed that positive results from the FIT did not differ significantly between individuals with SSA/P and those with non-advanced adenoma or those with negative findings from colonoscopy. Patients with large SSA/Ps were less likely to have positive results from the FIT than patients with advanced adenoma, with odds ratios of 0.44 (95% confidence interval [CI], 0.18-1.05), 0.30 (95% CI, 0.10-0.90), and 0.37 (95% CI, 0.12-1.12) at cutoffs of 10, 15, and 20 \u03bcg hemoglobin/g feces, respectively, after adjusting for lesion size, even with synchronous conventional adenoma.",
            "output": [
                "Does fecal Immunochemical Test detect Sessile Serrated Adenomas and Polyps With a Low Level of Sensitivity?"
            ]
        },
        {
            "id": "task847-675ecc801d1741628644827534a07086",
            "input": "Oxygen free radicals may be implicated in the pathogenesis of ischemia reperfusion damage. The beneficial effects of antioxidant nutrients, as well as complex plant extracts, on cerebral ischemia-reperfusion injuries are well known. This study was conducted to determine the effects of the hydro-alcoholic root extract of Withania coagulans on CA1 hippocampus oxidative damages following global cerebral ischemia/reperfusion in rat.', 'Male Wistar rats were randomly divided in five groups: control, sham operated, Ischemia/ Reperfiusion (IR), and Withania Coagulans Extract (WCE) 500 and 1000mg/kg + I/R groups. Ischemia was induced by ligation of bilateral common carotid arteries for 30 min after 30 days of WCE administration. Three days after, the animals were sacrificed, their brains were fixed for histological analysis (NISSL and TUNEL staining) and some samples were prepared for measurement of malondialdehyde (MDA) level and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity in hippocampus.', 'WCE showed neuroprotective activity by significant decrease in MDA level and increase in the SOD, CAT and GPx activity in pretreated groups as compared to I/R groups (p<0.001). The number of intact neurons was increased while the number of TUNEL positive neurons in CA1 hippocampal region in pretreated groups were decreased as compared to I/R group (p<0.001).",
            "output": [
                "Do neuroprotective effects of Withania coagulans root extract on CA1 hippocampus following cerebral ischemia in rats?"
            ]
        },
        {
            "id": "task847-156e6339392944518da7fb8824f110c1",
            "input": "The present study aimed to identify the relationship between glycemic variability (GV) and the 10-y risk of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) patients with good glycemic control.', 'Two-hundred forty consecutive T2DM patients (HbA1c\u22647.0%) without CVD were included to calculate the 10-y CVD risk by Framingham risk score (FRS), and divided into 3 groups: low-risk group (FRS\u226410%), intermediate-risk group (>10%, \u226420%) and high-risk group (>20%). Inter-group differences of GV were determined by comparing the SD of blood glucose (SDBG), mean amplitudes of glycemic excursion (MAGE), and mean of daily differences (MODD) gathered from 72-h continuous glucose monitoring system.', 'The levels of SDBG and MAGE significantly increased along with the raises of 10-y CVD risk of T2DM patients (p<0.01). FRS was positively correlated with age, systolic blood pressure, SDBG and MAGE (r=0.717, 0.525, 0.509 and 0.485 respectively, p<0.01), while negatively correlated with the level of HDL-C (r=-0.348, p<0.01). Furthermore, multivariate logistic regression analysis confirmed that increased MAGE [OR: 1.623(1.198-2.316), p<0.001] and patients with high urine albumin excretion rates [OR: 1.743(1.247-2.793), p<0.001] were independent predictors for high 10-y CVD risk.",
            "output": [
                "Is glycemic variability evaluated by continuous glucose monitoring system associated with the 10-y cardiovascular risk of diabetic patients with well-controlled HbA1c?"
            ]
        },
        {
            "id": "task847-09ef5513ab3c49e59c459120fd79692d",
            "input": "Prematurity and fetal growth restriction are risk factors for pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD). Neonatal rats develop PH and vascular remodeling when exposed to hyperoxia. We hypothesize that postnatal growth restriction (PNGR) due to under-nutrition increases the severity of PH induced by hyperoxia in neonatal rats.', \"Pups were randomized at birth to litters maintained in room air or 75% oxygen (hyperoxia), together with litters of normal milk intake (10 pups) or PNGR (17 pups). After 14 d, right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricular plus septal weight) and PH by echocardiography. Lungs were analyzed by immunohistochemistry, morphometrics, western blotting, and metabolomics.\", 'Hyperoxia and PNGR each significantly increased pulmonary arterial pressure, RVH and pulmonary arterial medial wall thickness, and significantly decreased pulmonary vessel number. These changes were significantly augmented in pups exposed to both insults. Hyperoxia and PNGR both significantly decreased expression of proteins involved in lung development and vasodilation.",
            "output": [
                "Does postnatal growth restriction augment oxygen-induced pulmonary hypertension in a neonatal rat model of bronchopulmonary dysplasia?"
            ]
        },
        {
            "id": "task847-1c00c0efcd48477fa52da399906f64df",
            "input": "Data on the association of memory performance with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are inconsistent. The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NB) is a commonly used validated cognitive tool; however, only few studies have examined its relationship with CSF biomarkers for AD. We studied the correlation of pathological changes in CSF biomarkers with various CERAD-NB subtests and total scores.\", 'Out of 79 subjects (36 men, mean age 70.5 years), 63 had undergone an assessment of cognitive status with CERAD-NB and a CSF biomarker analysis due to a suspected memory disorder, and 16 were controls with no memory complaint.', 'In women we found a significant correlation between CSF amyloid-beta (A\u03b21-42) and several subtests measuring delayed recall. Word List Recall correlated with all markers: A\u03b21-42 (r = 0.323, p = 0.035), tau (r = -0.304, p = 0.050) and hyperphosphorylated tau (r = -0.331, p = 0.046). No such correlations were found in men.",
            "output": [
                "Does low Cerebrospinal Fluid Amyloid-Beta Concentration be Associated with Poorer Delayed Memory Recall in Women?"
            ]
        },
        {
            "id": "task847-2d68da435c17485480b28db45336ece2",
            "input": "Emerging evidence has indicated the bad effect of periodontal inflammation on diabetes control. However, the exact regulatory mechanisms within the association between periodontitis and diabetic development remain unclear. This study aims to investigate the function of microRNAs in regulating periodontitis-induced inflammation in an obese rat model.', 'Experimental periodontitis was introduced into OLETF and LETO rat. Intraperitoneal glucose tolerance test was performed to detect diabetic development. Serum cytokines levels and microRNAs expression were detected by ELISA and RT-PCR analysis respectively. And, macrophages were isolated for gain- and loss-of-function studies, to investigate the regulatory mechanism of miR-147 in periodontitis-induced inflammation.', 'Periodontitis induced proinflammatory response with classical activated macrophages in both rats, but distinctively aggravated the impaired glucose tolerance of OLETF rat with spontaneous type 2 diabetes. Analysis for serum microRNAs expression showed the distinctive and synergistic upregulation of miR-147 with periodontitis-induced effects in rats, while further experiments demonstrated the positive regulatory mechanism of miR-147 on classical activated macrophages with overexpressed proinflammatory markers, showing M1 phenotype.",
            "output": [
                "Does periodontitis promote the diabetic development of obese rat via miR-147 induced classical macrophage activation?"
            ]
        },
        {
            "id": "task847-d43dcd68771a4c939884e20e9eabf289",
            "input": "Breast reconstruction (BR) following mastectomy for breast cancer has been shown to improve quality of life and body image; however, there is significant geographic variation in BR rates. We explored factors associated with BR following mastectomy.', 'This is a population-based data linkage study consisting of cancer registry records linked to hospital inpatient episodes for 4104 women aged 20\\u2009years and over-diagnosed with a first primary invasive localized stage breast cancer between 1997 and 2012 in Queensland, Australia, who underwent a mastectomy. Multivariate logistic regression was used to model predictors of BR.', 'Overall, 481 women (11.7%) underwent reconstruction. Proportions increased over time and were higher for younger women. Younger age, more recent diagnosis, living in high or very high accessibility areas or less disadvantaged areas, smaller tumours and attending a private or high-volume hospital independently increased the odds of reconstruction. The geographical disparity reduced significantly over time.",
            "output": [
                "Does geographical disparity in breast reconstruction following mastectomy have reduced over time?"
            ]
        },
        {
            "id": "task847-3cee4b6061cb49aea0eb83df731cdb5d",
            "input": "There are conflicting results for relationships between serum vitamin D levels and metabolic diseases. The aim of this study was to investigate whether serum vitamin D levels were associated with various metabolic diseases including insulin resistance (IR), metabolic syndrome (MS), fatty liver (FL), and coronary artery calcification (CAC), along with assessing gender differences for these relationships in Korean adults.', 'A total of 180,918 subjects (98,412 men and 82,506 women) who participated in a comprehensive health examination in the 2012-2013 period at Kangbuk Samsung Hospital, College of Medicine, Sungkyunkwan University were included. Serum vitamin D and metabolic markers were analyzed and CAC was estimated. Subjects were divided according to quartile groups of serum vitamin D. To examine the relationships of serum vitamin D to metabolic diseases and metabolic factors, multivariate logistic analysis was conducted.', 'High levels of serum vitamin D was associated with lower ORs for MS, IR and FL both in men and women (all p\\xa0<\\xa00.05). For men, ORs for CAC were significantly higher in third and the highest quartile groups for serum vitamin D in all the analyzed models (all p\\xa0<\\xa00.05). However, women showed no significant results between serum vitamin D and CAC.",
            "output": [
                "Are high levels of serum vitamin D associated with a decreased risk of metabolic diseases in both men and women , but an increased risk for coronary artery calcification in Korean men?"
            ]
        },
        {
            "id": "task847-1bc16cbb5d2f43a7bf3306e0358d86b1",
            "input": "Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far.', 'Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37). Additionally, we investigated progranulin expression in an LD mouse model as compared to wild-type mice. Moreover, we elucidated circulating progranulin before and during metreleptin supplementation in 10 patients with LD.', 'Median [interquartile range] circulating progranulin was increased in patients with LD (82.9 [25.9] \u03bcg/l) as compared to controls (73.6 [22.8] \u03bcg/l) (p=0.005). C-reactive protein (CRP) remained an independent and positive predictor of progranulin in multivariate analysis. Progranulin mRNA was significantly upregulated in all adipose tissue depots, i.e. visceral, subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild-type mice. Progranulin levels did not significantly change during metreleptin supplementation.",
            "output": [
                "Is progranulin increased in human and murine lipodystrophy?"
            ]
        },
        {
            "id": "task847-41644880c7f54844ab531c9305083f9a",
            "input": "To study the possible association of catechol-O-methyltransferase (COMT) Val158Met polymorphism with multiple and solitary uterine leiomyomas (ULs) and to check whether the COMT Val/Val genotype is associated with MED12 exon 2 mutations in fibroids.', 'The COMT Val158Met allele and genotype frequencies were compared between age-matched women with ULs (n=104) and controls (n=59). Patients with UL were subcategorised by diagnosis of solitary (n=59) or multiple (n=45) fibroids and by the presence of somatic MED12 exon 2 mutations in at least one fibroid (n=32) or in neither fibroid (n=26). The association of COMT Val/Val genotype with the presence of any ULs, solitary/multiple ULs and ULs positive/negative for MED12 exon 2 mutations was evaluated by \u03c7', 'The COMT Val/Val genotype frequency did not differ between the patients with UL and the controls (28.8% vs 18.6%, p=0.149, OR 1.77; CI 0.81 to 3.86). However, it was significantly higher in the patients who had multiple UL compared with the solitary UL (40% vs 20.3%, p=0.028, OR 2.61; CI 1.09 to 6.24) and to the controls (40% vs 18.6%, p=0.016, OR 2.91; CI 1.20 to 7.06). No association of the COMT Val/Val genotype with UL-specific MED12 exon 2 mutations was found (p=0.662, OR 0.77; CI 0.23 to 2.53).",
            "output": [
                "Is catechol-O-methyltransferase Val158Met polymorphism associated with increased risk of multiple uterine leiomyomas either positive or negative for MED12 exon 2 mutations?"
            ]
        },
        {
            "id": "task847-f0dcdab7591348c890ad64c728121002",
            "input": "MicroRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. We reported that levels of microRNA (miR)-29 family are decreased in corneas of patients with Fuchs endothelial corneal dystrophy (FECD). The miR-29 family regulates the production of extracellular matrix (ECM) proteins. Accumulation of ECM proteins in Descemet membrane is an important pathologic change in FECD. In this study, we transfected miR-29b into human corneal endothelial cells and tissues and evaluated ECM protein expression levels.', 'An immortalized Fuchs human corneal endothelial cell line (iFECD) was established by infection of corneal endothelial cells from patients with FECD with hTERT lentivirus. MiR-29b was transfected into iFECD, and the expression levels of ECMs collagen type 1 alpha 1 (COL1A1), collagen type 4 alpha 1 (COL4A1), and laminin gamma 1 (LAMC1) were evaluated with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot. Expression level of LAMC1 protein in miR-29b-transfected donor corneal endothelium was also evaluated by Western blot.', 'Compared with control, miR-29b expression level after transfection of iFECD was increased to 335.6% (\u00b191.0%), and ECM expression levels were significantly decreased. Compared with control, qRT-PCR demonstrated reduction of ECM to the following levels: COL1A1: 1.9% (\u00b10.4%); COL4A1: 7.1% (\u00b11.7%); and LAMC1: 21.5% (\u00b12.7%). Western blot showed reduced protein expression: COL1A1: 4.8% (\u00b13.2%); COL4A1: 42.5% (\u00b125.0%); and LAMC1: 44.8% (\u00b13.1%). In miR-29b-transfected corneal tissue, LAMC1 protein expression level was decreased to 14.4% (\u00b120.5%).",
            "output": [
                "Does microRNA-29b Overexpression decrease Extracellular Matrix mRNA and Protein Production in Human Corneal Endothelial Cells?"
            ]
        },
        {
            "id": "task847-b168f91e72ef4289a4beaf7fddeb1259",
            "input": "To study the ability of human spermatogonial stem cells (hSSCs) to proliferate in\\xa0vitro under mouse spermatogonial stem cell (mSSC) culture conditions.', 'Experimental basic science study.', 'Reproductive biology laboratory.', 'Cryopreserved testicular tissue with normal spermatogenesis obtained from three donors subjected to orchiectomy due to a prostate cancer treatment.', 'Testicular cells used to create in\\xa0vitro cell cultures corresponding to the following groups: [1] unsorted human testicular cells, [2] differentially plated human testicular cells, and [3] cells enriched with major histocompatibility complex class 1 (HLA', 'Analyses and characterization including immunocytochemistry and quantitative reverse-transcription polymerase chain reaction for somatic and germ cell markers, testosterone and inhibin B quantification, and TUNEL assay.', 'Putative hSSCs appeared in singlets, doublets, or small groups of up to four cells in\\xa0vitro only when testicular cells were cultured in StemPro-34 medium supplemented with glial cell line-derived neurotrophic factor (GDNF), leukemia inhibitory factor (LIF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF). Fluorescence-activated cell sorting with HLA",
            "output": [
                "Do human spermatogonial stem cells display limited proliferation in vitro under mouse spermatogonial stem cell culture conditions?"
            ]
        },
        {
            "id": "task847-db6fe7fcd98749f097b8f3a4f32bdd68",
            "input": "To identify the risk factors for suboptimal response to GnRH agonist (GnRH-a) trigger and evaluate the effect of hCG on the outcome of patients with suboptimal response to GnRH-a.', 'A retrospective data analysis.', 'A tertiary-care academic medical center.', 'A total of 8,092 women undergoing 8,970 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles.', 'All women underwent hMG + medroxyprogesterone acetate (MPA)/P treatment cycles during IVF/ICSI, which were triggered using a GnRH-a alone or in combination with hCG (1,000, 2,000, or 5,000 IU). Viable embryos were cryopreserved for later transfer.', 'The rates of oocyte retrieval, mature oocytes, fertilization, and the number of oocytes retrieved, mature oocytes, and embryos frozen.', 'In total, 2.71% (243/8,970) of patients exhibited a suboptimal response to GnRH-a. The suboptimal responders (LH \u226415 mIU/mL) had a significantly lower oocyte retrieval rate (48.16% vs. 68.26%), fewer mature oocytes (4.10 vs. 8.29), and fewer frozen embryos (2.32 vs. 3.54) than the appropriate responders. Basal LH levels served as the single most valuable marker for differentiating suboptimal responders with the areas under the receiver operating curve of 0.805. Administering dual trigger (GnRH-a and hCG 1,000, 2,000, 5,000 IU) significantly increased oocyte retrieval rates (60.04% vs. 48.16%; 68.13% vs. 48.16%; and 65.76% vs. 48.16%, respectively) in patients with a suboptimal response.",
            "output": [
                "Does dual trigger for final oocyte maturation improve the oocyte retrieval rate of suboptimal responders to gonadotropin-releasing hormone agonist?"
            ]
        },
        {
            "id": "task847-f8f95305e56c49fbaee579f134bc5afa",
            "input": "Insulin resistance is correlated with the progress of albuminuria in diabetic patients, and podocytes are crucial for maintaining the normal function of the glomerular filtration barrier. In the present study, we aimed to investigate the high glucose-induced insulin resistance and cell injury in human podocytes and the putative role of autophagy in this process.', 'Human podocytes were cultured in high glucose-supplemented medium and low glucose and high osmotic conditions were used for the controls. Autophagy in the podocytes was regulated using rapamycin or 3-methyladenine stimulation. Next, autophagy markers including LC3B, Beclin-1, and p62 were investigated using western blot and qPCR, and the insulin responsiveness was analyzed based on glucose uptake and by using the phosphorylation of the insulin receptor with Nephrin as a podocyte injury marker.', 'The basal autophagy level decreased under the high glucose conditions, which was accompanied by a decrease in the glucose uptake and phosphorylation of the insulin receptor in the human podocytes. More interestingly, the glucose uptake and the phosphorylation of the insulin receptor were decreased by 3-MA stimulation and increased by rapamycin, illustrating that the responsiveness of insulin was regulated by autophagy. The activation of autophagy by rapamycin also ameliorated cell injury in the human podocytes.",
            "output": [
                "Does autophagy protect human podocytes from high glucose-induced injury by preventing insulin resistance?"
            ]
        },
        {
            "id": "task847-a1aeaa88cd0e4e1796c52a6ffe377fe9",
            "input": "Apolipoprotein D (ApoD) is a member of the lipocalin family known to transport small hydrophobic ligands. A major site of ApoD expression in mice is the central nervous system where evidence suggests that it plays a protective role. Gene expression of ApoD was reported in bone-forming osteoblasts but its impact on bone metabolism remains undocumented.', 'We compared basic bone parameters of ApoD(-/-) (null) and transgenic (tg) mice to wild-type (wt) littermates through microCT and histochemistry, as well as ApoD expression and secretion in osteoblasts under various culture conditions through real-time PCR and immunoblotting.', 'ApoD-null females displayed progressive bone loss with aging, resulting in a 50% reduction in trabecular bone volume and a 23% reduction in cortical bone volume by 9months of age. Only cortical bone volume was significantly reduced in ApoD-null males by an average of 24%. Histochemistry indicated significantly higher osteoblast surface and number of osteoclasts in femora from ApoD-null females. ApoD gene expression was confirmed in primary cultures of bone marrow mesenchymal cells (MSC), with higher expression levels in MSC from females compared to males. ApoD-null MSC exhibited impaired proliferation and differentiation potentials. Moreover, exogenous ApoD partially rescued the osteogenic potential of null MSC, which were shown to readily uptake the protein from media. ApoD expression was upregulated under low proliferation conditions, by contact inhibition and osteoblastic differentiation in MC3T3-E1 osteoblast-like cells.",
            "output": [
                "Is apolipoprotein D deficiency associated to high bone turnover , low bone mass and impaired osteoblastic function in aged female mice?"
            ]
        },
        {
            "id": "task847-179bb8a8b7e045c5b3b6b97279c11933",
            "input": "Obese twins have lower saturated and higher long-chain polyunsaturated fatty acids (FA) in subcutaneous adipose tissue (SAT) compared to their lean monozygotic (MZ) co-twin. Whether this holds for metabolically distinct deep (DSAT) and superficial (SSAT) depots is unknown. Here we use non-invasive magnetic resonance spectroscopy (MRS) to measure the FA unsaturation in body mass index (BMI) discordant MZ twins in DSAT and SSAT and their relationship to ectopic fat content and body fat distribution. The main finding is further confirmed in an independent cohort using standardized measurement times.', 'MRS and magnetic resonance imaging were used to measure DSAT and SSAT unsaturation and their relationship to intramyocellular lipids (IMCL), hepatocellular lipids (HCL) and the amount of subcutaneous (SAT) and visceral adipose tissue (VAT) in 16 pairs of healthy monozygotic twins (MZ) discordant for BMI. A second independent cohort of 12 healthy volunteers was used to measure DSAT unsaturation and IMCL with standardized measurement time. One volunteer also underwent repeated random measurements of DSAT unsaturation and IMCL.', 'In accordance with biopsy studies SSAT unsaturation was higher in the heavier twins (15.2\u00b11.0% vs. 14.4\u00b11.5%, P=0.024) and associated with SAT volume (R=0.672, P=0.001). DSAT unsaturation did not differ between twins (11.4\u00b10.8 vs. 11.0\u00b11.0, P=0.267) and associated inversely with IMCL content (R=-0.462, P=0.001). The inverse association between DSAT unsaturation and IMCL was also present in the participants of the second cohort (R=-0.641, P=0.025) and for the repeated sampling at random of one person (R=-0.765, P=0.027).",
            "output": [
                "Does deep subcutaneous adipose tissue lipid unsaturation associate with intramyocellular lipid content?"
            ]
        },
        {
            "id": "task847-fd996dd24c5e417e8d288201c81a222e",
            "input": "Ischemia/reperfusion (I/R) injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure (ARF). The ischemic ARF in diabetic rats is much more severe than that in the normal rats exposed to as same ischemic time. Ischemic post-conditioning (IPO) is a phenomenon by which intermittent interruptions of blood flow in the early phase of reperfusion can protect organs from I/R injury. To determine whether the renal protection effect of IPO mediates by toll-like receptor 4 (TLR4) signaling pathway in diabetic rats.', 'Streptozotocin-induced diabetic rats were randomly divided into three groups: sham operation group, I/R group, and IPO group. Except sham operation group, rats were subjected to 30\\u2009min of renal ischemia, both with and without treatment with IPO, then reperfusion 24\\u2009h. Light microscope and transmission electronic microscope were used to observe structural changes of renal tubule. RT-PCR was used to measure TLR4 and tumor necrosis factor-alpha (TNF-\u03b1) mRNA expression level, renal TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) protein expression was detected by Western blot.', 'The results demonstrated that IPO markedly decreased renal ischemic injury caused by I/R and inhibited the proinflammatory expression levels of TLR4, TNF-\u03b1, and NF-\u03baB, all of which up-regulated by I/R in diabetic rats.",
            "output": [
                "Does ischemic post-conditioning attenuate renal ischemic reperfusion injury via down-regulation of toll-like receptor 4 in diabetic rats?"
            ]
        },
        {
            "id": "task847-82aafc1361ce45518aab190e26e07104",
            "input": "Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine. Recently, several studies have shown that MSCs can be easily isolated from human amnion. In this study, we investigated the therapeutic effect of transplantation of human amnion-derived MSCs (hAMSCs) in rats with liver fibrosis.', 'Liver fibrosis was induced by an intraperitoneal injection of 2 mL/kg of 50% carbon tetrachloride twice a week for 6 weeks. At 3 weeks, hAMSCs (1 \u00d7 10(6) cells) were transplanted intravenously. Rats were sacrificed at 7 weeks, and histological analyses and quantitative reverse-transcription polymerase chain reaction were performed. In vitro experiments were conducted to investigate the effect of hAMSCs on the activation of Kupffer cells.', 'Transplantation of hAMSCs significantly reduced the fibrotic area, deposition of type-I collagen, the number of \u03b1-smooth muscle actin-positive hepatic stellate cells, and CD68-positive Kupffer cells in the livers. messenger RNA expression of \u03b1-smooth muscle actin and tissue inhibitor of metalloproteinase-1 was significantly decreased and the expression of matrix metalloproteinase-9 and hepatocyte growth factor was significantly increased in the liver of hAMSC-treated rats. Transplantation of hAMSCs at 3 weeks plus 5 weeks did not have an additive effect. In vitro experiments demonstrated that Kupffer cell activation induced by lipopolysaccharide was significantly decreased by culturing with conditioned medium obtained from hAMSCs.",
            "output": [
                "Does human Amnion-Derived Mesenchymal Stem Cell Transplantation ameliorate Liver Fibrosis in Rats?"
            ]
        },
        {
            "id": "task847-c4a946e7d0fd4f45acf3981f64c58756",
            "input": "There is a critical need to better preserve isolated organs before transplantation. We developed a novel nonerythropoiesis cyclic helix B peptide (CHBP) derived from erythropoietin, which has potent tissue protection and prolonged serum stability. The renoprotection and potential mechanism of CHBP were evaluated in a kidney preservation model.', 'Porcine kidneys (n = 5) subjected to 20-minute warm ischemia were retrieved and flushed with hyperosmolar citrate to mimic deceased donation. The kidneys and autologous blood \u00b1 10.56 nmol/L CHBP were placed in cold storage (CS) for 18 hours. These kidneys were then normothermically hemoreperfused for 3 hours using an isolated organ perfusion system. The renal function and structure, apoptosis, inflammation, and expression of caspase-3 and heat shock protein 70 (HSP70) were assessed.', 'Cyclic helix B peptide significantly increased the renal blood flow, oxygen consumption, and urine output during reperfusion, but decreased serum potassium and renal tissue damage. Apoptotic cells were significantly decreased in the tubular areas, but increased in the lumens and interstitial areas in the post-CS and postreperfused kidneys, whereas myeloperoxidase+ cells were reduced. In addition, the expression of both caspase-3 precursor and active subunits was downregulated by CHBP in reperfused kidneys. However, HSP70 was upregulated in the post-CS and postreperfused kidneys treated with CHBP.",
            "output": [
                "Does cyclic Helix B Peptide in Preservation Solution and Autologous Blood Perfusate ameliorate Ischemia-Reperfusion Injury in Isolated Porcine Kidneys?"
            ]
        },
        {
            "id": "task847-78b8e7a48c2f4467ad04c9de9f0b69bc",
            "input": "To evaluate rotavirus vaccination in Malaysia from the household's perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies the broader value of universal vaccination starting with non-health benefits such as financial risk protection and equity. These dimensions better enable decision-makers to evaluate policy on the public finance of health programmes.\", 'The incidence, health service utilisation and household expenditure related to rotavirus gastroenteritis according to national income quintiles were obtained from local data sources. Multiple birth cohorts were distributed into income quintiles and followed from birth over the first five years of life in a multicohort, static model.', 'We found that the rich pay more out of pocket (OOP) than the poor, as the rich use more expensive private care. OOP payments among the poorest although small are high as a proportion of household income. Rotavirus vaccination results in substantial reduction in rotavirus episodes and expenditure and provides financial risk protection to all income groups. Poverty reduction benefits are concentrated amongst the poorest two income quintiles.",
            "output": [
                "Do rotavirus vaccines contribute towards universal health coverage in a mixed public-private healthcare system?"
            ]
        },
        {
            "id": "task847-eb200cabbc08417a9588c0af95b01dd9",
            "input": "Arterial age can be estimated from equations relating arterial stiffness to age and blood pressure in large cohorts. We investigated whether estimated arterial age (eAA) was elevated in patients with the metabolic syndrome and/or known cardiovascular disease (CVD), which factors were associated with eAA and whether eAA added prognostic information.', 'In 1993, 2366 study participants, 41, 51, 61, and 71 years old, had traditional cardiovascular risk factors and carotid-femoral pulse wave velocity (cfPWV) measured. Risk groups were identified based on known CVD and components of metabolic syndrome, Systematic COronary Risk Evaluation, or Framingham risk score. From age, mean blood pressure, and cfPWV, eAA and estimated cfPWV (ePWV) were calculated. In 2006, the combined cardiovascular endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for ischemic heart disease was registered.', 'cfPWV and ePWV increased with ageing and cardiovascular risk (all P\\u200a<\\u200a0.001), but ePWV increased more with ageing than cfPWV. The difference between eAA and chronological age was associated with male sex (\u03b2\\u200a=\\u200a0.14), higher heart rate (\u03b2\\u200a=\\u200a0.16 both P\\u200a<\\u200a0.001), fasting glucose (\u03b2\\u200a=\\u200a0.08) soluble urokinase plasminogen activator receptor (\u03b2\\u200a=\\u200a0.06, both P\\u200a<\\u200a0.01), and known CVD (\u03b2\\u200a=\\u200a0.06, P\\u200a<\\u200a0.05) independently of age, SBP, and heart rate. Independently of Systematic COronary Risk Evaluation, eAA (hazard ratio\\u200a=\\u200a1.20, P\\u200a<\\u200a0.01) predicted CEP, but not as accurately as ePWV (hazard ratio\\u200a=\\u200a1.58, P\\u200a<\\u200a0.001) and cfPWV (hazard ratio\\u200a=\\u200a1.32, P\\u200a<\\u200a0.001) among apparently healthy study participants.",
            "output": [
                "Is elevated estimated arterial age associated with metabolic syndrome and low-grade inflammation?"
            ]
        },
        {
            "id": "task847-72e8871a9fcf447eb2b2447a92a826b5",
            "input": "As metoclopramide stimulates aldosterone secretion, we tested its usefulness in the assessment of lateralization of primary aldosteronism by adrenal vein sampling (AVS).', 'Prospective within-patient study in consecutive patients undergoing AVS for primary aldosteronism subtyping.', 'We compared the diagnostic accuracy of baseline and postmetoclopramide lateralization index and relative (to cortisol) aldosterone secretion indices (RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined by the four corners criteria as the reference diagnosis.', 'We recruited 93 consecutive patients (mean age: 52 years; women 31%). Metoclopramide increased plasma aldosterone in the inferior vena cava and in both adrenal veins. The postmetoclopramide lateralization index was accurate in identifying APA, but did not increase diagnostic accuracy over baseline lateralization index, because the RASI increased similarly in both sides. Conversely, metoclopramide raised RASI to values more than 0.90 bilaterally in non-APA patients allowing accurate identification of factitious aldosterone suppression. In contrast, RASI was 0.90 or less in 48% contralateral to the tumor in APA patients. Regression analysis showed the APA patients with persistent suppression of RASI contralaterally showed a more florid primary aldosteronism phenotype.",
            "output": [
                "Does metoclopramide unmask potentially misleading contralateral suppression in patients undergoing adrenal vein sampling for primary aldosteronism?"
            ]
        },
        {
            "id": "task847-9d8ee0b0fb5c45029bfc506770170de2",
            "input": "Flow-diverter stents (FDS) are new devices for the endovascular treatment of intracranial aneurysms (IAs) promoting progressive aneurysmal thrombosis. To date, the delay of aneurysmal exclusion remains unclear. We evaluated the correlation between angiographic changes in the first 24 hours and 12-month occlusion in aneurysms treated with FDS.', 'We retrospectively analyzed the intra-aneurysmal flow by evaluating the in-flow and out-flow delays on preoperative, immediate postoperative, 24-hour and 12-month follow-up angiography. Dichotomy of in-flow and out-flow within the aneurysm was considered as the time of contrast filling and time of contrast washing relatively to the parent artery. The delay times were compared and correlated with the therapeutic success of FDS at 12 months of follow-up.', 'Out of 14 treated IAs, in 13 consecutive patients, n\\u2009=\\u200910 (71%) aneurysms showed complete occlusion at 12 months. Between immediate postoperative and 24-hour control, 10 aneurysms (71%) demonstrated in-flow modification, with eight increasing, two decreasing and four having no change. There were no statistical differences in therapeutic success in relation to the different flow-related profiles of intra-aneurysmal flux.Out-flow modifications were found in 11 aneurysms (79%) between immediate postoperative and 24-hour control, with five increasing, six decreasing and three having no change. Similar to the in-flow changes, there were no statistical differences in therapeutic success relative to the flow-related profiles.",
            "output": [
                "Are early angiographic changes of intra-aneurysmal flow after flow-diverter stent treatment predictive of therapeutic success?"
            ]
        },
        {
            "id": "task847-496e25a71027424e87e3583a1fab147f",
            "input": "\u03b21-Adrenergic receptor (\u03b21-AR) stimulation modulates the antiarrhythmic activities of sodium channel blockers. The \u03b21-AR Gly389 variant shows a marked decrease in agonist-stimulated cyclic AMP production compared with that of the wild-type Arg389 in vitro. We investigated whether the Arg389Gly polymorphism affects the efficacy of flecainide, a typical sodium channel blocker, in patients with or without coadministration of \u03b2-blockers.', 'The effects of the \u03b21-AR Arg389Gly polymorphism on the antiarrhythmic efficacy of flecainide were compared between with and without coadministered \u03b2-blockers in 159 patients with supraventricular tachyarrhythmia. The antiarrhythmic efficacy of flecainide was assessed for at least 2 months by evaluating symptomatology, 12-lead ECGs, and Holter monitoring results.', 'Genetic differences in the antiarrhythmic efficacy of flecainide were observed in patients with coadministration of \u03b2-blockers. Tachyarrhythmia was well controlled in 60% of Arg389-homozygotes, 30% of Gly389-heterozygotes, and 0% of Gly389-homozygotes (P=0.001). In contrast, no difference in the antiarrhythmic efficacy was observed among the three genotypes in the patients without coadministration of \u03b2-blockers (64, 70, and 60%, respectively). Heart rate in tachyarrhythmia in patients treated with flecainide was significantly higher in Gly389 carriers than in Arg389-homozygotes (P=0.013).",
            "output": [
                "Does \u03b21-Adrenergic receptor Arg389Gly polymorphism affect the antiarrhythmic efficacy of flecainide in patients with coadministration of \u03b2-blockers?"
            ]
        },
        {
            "id": "task847-47f3aaeecae74ed38878c33575a7da0a",
            "input": "Retinal vascular disease represents a major cause for vision loss in the Western world. Recent research has shown that neuronal and vascular damage are closely related in retinal disease. Ciliary neurotrophic factor (CNTF) is a well-studied neurotrophic factor that is currently being tested in clinical trials for the treatment of retinal degenerative diseases and macular telangiectasia. However, little is known about its effect on retinal vasculature. In this study, we investigate the effects of CNTF in retinal neovascular disease using the mouse model of oxygen-induced retinopathy (OIR).', 'Newborn pups were exposed to 75% oxygen from postnatal day (P)7 to P12 and subsequently returned to room air. Ciliary neurotrophic factor was injected intravitreally at OIR P12 and the vaso-obliterated and neovascular areas were quantified at OIR P17. Immunohistochemistry, RNA, and protein analysis were used to identify CNTF-responsive cells. In vitro experiments were performed to analyze the effect of CNTF on endothelial and astroglial cells.', 'In the OIR model, CNTF facilitated capillary regrowth and attenuated preretinal neovascularization in a dose-dependent manner. The protective effect of CNTF was mediated via activation of the JAK/STAT3/SOCS3 signaling pathway. Immunohistochemical studies identified endothelial cells among others as CNTF-responsive cells in the retina. In vitro studies confirmed the anti-angiogenic effect of CNTF on endothelial cell sprouting.",
            "output": [
                "Does cNTF attenuate Vasoproliferative Changes Through Upregulation of SOCS3 in a Mouse-Model of Oxygen-Induced Retinopathy?"
            ]
        },
        {
            "id": "task847-1ab1f0cfbf024198b86722106720249a",
            "input": "Inadequate apoptosis of fibroblast-like synoviocytes (FLS) plays a crucial role in the immunopathogenesis of rheumatoid arthritis (RA). Interleukin-22 (IL-22) is a novel member of the cytokine network that has been found to be involved in the immunological process underlying RA. In this study, we investigated the effect of IL-22 on the survival of RA-FLS from RA patients and examined the possible mechanism to determine new therapeutic strategies for RA.', 'FLS obtained from patients with RA were cultured in vitro and treated with sodium nitroprussiate (SNP) to induce apoptosis in the presence or absence of IL-22. RA-FLS viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RA-FLS apoptosis was analyzed by annexin V/propidium iodide staining (AV/PI). The levels of IL-22R1, pSTAT3-Y705, pSTAT3-S727, total STAT3, Bcl-xL and Bcl-2 were detected by Western blot analysis.', 'IL-22R1 was expressed on RA-FLS. IL-22 pretreatment at concentrations ranging from 10 to 100 ng/mL increased RA-FLS viability and prevented SNP-induced apoptosis. Treatment with the STAT3 inhibitors, HO3867 or STA21, reversed the protective effect of IL-22 on SNP-induced apoptosis of RA-FLS. IL-22-induced phosphorylation of STAT3 (pSTAT3-Y705 and pSTAT3-S727) was increased in RA-FLS. Also IL-22 increased Bcl-2 expression in SNP-treated RA-FLS, and the effect was reversed by treatment with HO3867 or STA21.",
            "output": [
                "Is anti-apoptotic effect of interleukin-22 on fibroblast-like synoviocytes in patients with rheumatoid arthritis mediated via the signal transducer and activator of transcription 3 signaling pathway?"
            ]
        },
        {
            "id": "task847-93c6ce2a36c64ca3b20ed372892287f8",
            "input": "Modular junctions are ubiquitous in contemporary hip arthroplasty. The head-trunnion junction is implicated in the failure of large diameter metal-on-metal (MoM) hips which are the currently the topic of one the largest legal actions in the history of orthopaedics (estimated costs are stated to exceed $4 billion). Several factors are known to influence the strength of these press-fit modular connections. However, the influence of different head sizes has not previously been investigated. The aim of the study was to establish whether the choice of head size influences the initial strength of the trunnion-head connection.', 'Ti-6Al-4V trunnions (n = 60) and two different sizes of cobalt-chromium (Co-Cr) heads (28\\u2008mm and 36\\u2008mm; 30 of each size) were used in the study. Three different levels of assembly force were considered: 4 kN; 5 kN; and 6 kN (n = 10 each). The strength of the press-fit connection was subsequently evaluated by measuring the pull-off force required to break the connection. The statistical differences in pull-off force were examined using a Kruskal-Wallis test and two-sample Mann-Whitney U test. Finite element and analytical models were developed to understand the reasons for the experimentally observed differences.', '36\\u2008mm diameter heads had significantly lower pull-off forces than 28\\u2008mm heads when impacted at 4\\u2008kN and 5\\u2008kN (p\\u2008<\\u20080.001; p\\u2008<\\u20080.001), but not at 6\\u2008kN (p\\u2008=\\u20080.21). Mean pull-off forces at 4 kN and 5\\u2008kN impaction forces were approximately 20% larger for 28\\u2008mm heads compared with 36\\u2008mm heads. Finite element and analytical models demonstrate that the differences in pull-off strength can be explained by differences in structural rigidity and the resulting interface pressures.",
            "output": [
                "Do large-diameter total hip arthroplasty modular heads require greater assembly forces for initial stability?"
            ]
        },
        {
            "id": "task847-70654e59a0aa445ab595419202bc4919",
            "input": "Mutations in FLG, which encodes profilaggrin, cause ichthyosis vulgaris (IV) and are an important predisposing factor for atopic dermatitis (AD). IV shows autosomal hemidominant (semidominant) inheritance, and patients with bi-allelic FLG mutations tend to have severe IV phenotypes. However, the effect of bi-allelic FLG mutations on AD incidence and severity remains a subject of controversy.', 'In this study, we studied individuals with bi-allelic null FLG mutations to elucidate the effect of bi-allelic FLG mutations on AD incidence and severity.', 'Six individuals with bi-allelic FLG null mutations from three families of IV/AD were investigated. We report the detailed clinical features of the individuals. The phenotype was confirmed by the clinical examinations and the severity of IV and AD was scored using ichthyosis score and Eczema Area and Severity Index (EASI).', 'It was found that five of the six patients had severe IV, and the remaining patient showed moderate IV. Two of the six had moderate AD and three of the six had mild AD. The remaining patient had no AD.",
            "output": [
                "Do compound heterozygotes for filaggrin gene mutations always show severe atopic dermatitis?"
            ]
        },
        {
            "id": "task847-5801e4047305413caa288abf38c2dcbe",
            "input": "Direct interaction between Red blood cells (RBCs) and platelets is known for a long time. The bleeding time is prolonged in anemic patients independent of their platelet count and could be corrected by transfusion of RBCs, which indicates that RBCs play an important role in hemostasis and platelet activation. However, in the last few years, opposing mechanisms of platelet inhibition by RBCs derived nitric oxide (NO) were proposed. The aim of our study was to identify whether RBCs could produce NO and activate soluble guanylate cyclase (sGC) in platelets.', \"To test whether RBCs could activate sGC under different conditions (whole blood, under hypoxia, or even loaded with NO), we used our well-established and highly sensitive models of NO-dependent sGC activation in platelets and activation of purified sGC. The activation of sGC was monitored by detecting the phosphorylation of Vasodilator Stimulated Phosphoprotein (VASP(S239)) by flow cytometry and Western blot. ANOVA followed by Bonferroni's test and Student's t-test were used as appropriate.\", 'We show that in the whole blood, RBCs prevent NO-mediated inhibition of ADP and TRAP6-induced platelet activation. Likewise, coincubation of RBCs with platelets results in strong inhibition of NO-induced sGC activation. Under hypoxic conditions, incubation of RBCs with NO donor leads to Hb-NO formation which inhibits sGC activation in platelets. Similarly, RBCs inhibit activation of purified sGC, even under conditions optimal for RBC-mediated generation of NO from nitrite.",
            "output": [
                "Do erythrocytes activate purified and platelet soluble guanylate cyclases even in conditions favourable for NO synthesis?"
            ]
        },
        {
            "id": "task847-01ab250efd6446fb8bf7ce52c02aed7c",
            "input": "Crohn's Disease (CD), a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn's ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS)-induced ileitis rats.\", 'Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48), an equal volume of 30% Ethanol (n = 24), and Saline (n = 24), respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR) to 20, 40, 60, 80, and 100 mmHg colorectal distension pressure (CRD) at day 1, 3, 7, 14, 21, and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-\u03b1, IL-1\u03b2, IL-6), and dorsal root ganglia (T11) for determination of calcitonin gene-related peptide by immunohistochemistry, respectively.', 'Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05) VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05) in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.",
            "output": [
                "Does visceral Hypersensitivity be Provoked by 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Ileitis in Rats?"
            ]
        },
        {
            "id": "task847-6f67841826434dd3a7020359ebb05c4c",
            "input": "Sei-1 is an oncogene capable of inducing double minute chromosomes (DMs) formation. DMs are hallmarks of amplification and contribute to oncogenesis. However, the mechanism of Sei-1 inducing DMs formation remains unelucidated.', 'DMs formation significantly increased during serial passage in vivo and gradually decreased following culture in vitro. micro nuclei (MN) was found to be responsible for the reduction. Of the DMs-carrying genes, Met was found to be markedly amplified, overexpressed and highly correlated with DMs formation. Inhibition of Met signaling decreased the number of DMs and reduced the amplification of the DMs-carrying genes. We identified a 3.57Mb DMs representing the majority population, which consists of the 1.21 Mb AMP1 from locus 6qA2 and the 2.36 Mb AMP2 from locus 6qA2-3.', 'We employed NIH-3T3 cell line with Sei-1 overexpression to monitor and characterize DMs in vivo and in vitro. Array comparative genome hybridization (aCGH) and fluorescence in situ hybridization (FISH) were performed to reveal amplification regions and DMs-carrying genes. Metaphase spread was prepared to count the DMs. Western blot and Met inhibition rescue experiments were performed to examine for involvement of altered Met signaling in Sei-1 induced DMs. Genomic walking and PCR were adopted to reveal DMs structure.",
            "output": [
                "Does met promote the formation of double minute chromosomes induced by Sei-1 in NIH-3T3 murine fibroblasts?"
            ]
        },
        {
            "id": "task847-1febf75253fe4a5fa7e749a2c59fce96",
            "input": "Obese persons have low circulating natriuretic peptide (NP) concentrations. It has been proposed that this 'natriuretic handicap' could play a role in obesity-related hypertension. The normal physiological response of the NP system to an increase in blood pressure (BP) is an increase in NP secretion with concomitant higher circulating NP concentrations. In this study, we investigated whether higher BP would also be related to higher circulating NP concentrations in obese men; furthermore, we verified that BP had affected the hearts of our study participants, by determining left ventricular mass (LVM).\", 'We examined 103 obese healthy medication-free men. We measured 24-hour ambulatory BP (ABP). LVM was calculated using the Cornell voltage-duration product method. Fasting serum concentrations of midregional proatrial NP (MR-proANP), a surrogate for active ANP, were measured. Linear regression analysis was used to calculate age-adjusted standardised regression coefficients (\u03b2).', 'LVM and BP increased across systolic ABP quartiles (mean LVM\u00b1SD: 1599.1\u00b1387.2\\u2005mm\\u2005ms in first vs 2188.5\u00b1551.3\\u2005mm\\u2005ms in fourth quartile, p<0.001; mean systolic ABP\u00b1SD: 114.5\u00b14.2\\u2005mm\\u2005Hg in first vs 149.0\u00b17.7\\u2005mm\\u2005Hg in fourth quartile, p<0.001). Systolic ABP was robustly associated with LVM (\u00df=0.48, p<0.001). Despite evidence of BP-related increases in LVM, serum MR-proANP was negatively associated with systolic ABP (\u00df=-0.32, p=0.004) and with diastolic ABP (\u00df=-0.45, p<0.001).",
            "output": [
                "Does serum proatrial natriuretic peptide increase with higher systolic blood pressure in obese men?"
            ]
        },
        {
            "id": "task847-7bb788b16a544042a36acbcd664b9d9d",
            "input": "The aim of this study is to establish follow-up protocols for adult patients with common variable immunodeficiency (CVID) in a recently founded adult immunology clinic in the Central Anatolia Region of Turkey, where a clinical immunology center for adults was not available previously.', 'A total of 25 patients with CVID aged 18 years and older were included in this study. The file format consisted of 13 pages and was developed for the purpose of the study. Separate sections were designated for identity information, medical history, disease course, previous and current laboratory and imaging studies, follow-up plans, detection and management of complications/comorbidities, and treatment results.', 'The mean age of the patients was 36.6 \u00b1 13.4 years. The delay in diagnosis was 107 \u00b1 95.6 months. In 92% of patients, initial symptoms resulting in admission to healthcare facilities were infections. Seventeen of 25 patients (68%) had bronchiectasis at the beginning of follow-up.",
            "output": [
                "Does common variable immunodeficiency in adults require reserved protocols for long-term follow-up?"
            ]
        },
        {
            "id": "task847-8be094682a264a1ea2209d33b2cc3c2b",
            "input": "Although the significance of cell cycle checkpoints in overcoming low-dose hyper-radiosensitivity (HRS) has been proposed, the underlying mechanism of HRS in human hepatocellular cells remains unclear. Therefore, the aim of this study was to characterize HRS inhuman hepatocellular HepG2 cells and to explore the molecular mechanism(s) mediating this response.', 'HepG2 cells were exposed to various single doses of \u03b3 radiation (from 0\\u2009Gy to 4\\u2009Gy), and then were assayed at subsequent time-points. Survival curves were then generated using a linear-quadratic (LQ) equation and a modified induced repair model (MIRM). The percentage of cells in the G1, G2/M, and S phases of the cell cycle were also examined using propidium iodide (PI) staining and flow cytometry. Levels of total cell division cyclin 25C (Cdc25C) and phosphorylated Cdc25C were examined by Western blotting.', 'Low-dose \u03b3 radiation (<0.3\\u2009Gy) induced HRS in HepG2 cells, while doses of 0.3, 0.5, and 2.0\\u2009Gy \u03b3 radiation significantly arrested HepG2 cells in the G2/M phase. While total Cdc25C levels remained unchanged after irradiation, levels of phosphorylated Cdc25C markedly increased 6, 16, and 24\\u2009h after treatment with 0.5 or 2.0\\u2009Gy radiation, and they peaked after 16\\u2009h. The latter observation is consistent with the G2/M arrest that was detected following irradiation.",
            "output": [
                "Is low-dose hyper-radiosensitivity in human hepatocellular HepG2 cells associated with Cdc25C-mediated G2/M cell cycle checkpoint control?"
            ]
        },
        {
            "id": "task847-24398ab7c4d547fd990f3239a565b1b5",
            "input": "Apelin-13 (A13) regulates cardiac homeostasis. However, the effects and mechanism of A13 infusion after an acute myocardial injury (AMI) have not been elucidated. This study assesses the restorative effects and mechanism of A13 on the peri-infarct region in murine AMI model.', '51 FVB/N mice (12weeks, 30g) underwent AMI. A week following injury, continuous micro-pump infusion of A13 (0.5\u03bcg/g/day) and saline was initiated for 4-week duration. Dual contrast MRI was conducted on weeks 1, 2, 3, and 5, consisting of delayed-enhanced and manganese-enhanced MRI. Four mice in each group were followed for an extended period of 4weeks without further infusion and underwent MRI scans on weeks 7 and 9.', \"A13 infusion demonstrated preserved LVEF compared to saline from weeks 1 to 4 (21.9\u00b13.2% to 23.1\u00b11.7%* vs. 23.5\u00b11.7% to 16.9\u00b12.8%, *p=0.02), which persisted up to 9weeks post-MI (+1.4%* vs. -9.4%, *p=0.03). Mechanistically, dual contrast MRI demonstrated significant decrease in the peri-infarct and scar % volume in A13 group from weeks 1 to 4 (15.1 to 7.4% and 34.3 to 25.1%, p=0.02, respectively). This was corroborated by significant increase in 5-ethynyl-2'-deoxyuridine (EdU(+)) cells by A13 vs. saline groups in the peri-infarct region (16.5\u00b13.1% vs. 8.1\u00b11.6%; p=0.04), suggesting active cell mitosis. Finally, significantly enhanced mobilization of CD34(+) cells in the peripheral blood and up-regulation of APJ, fibrotic, and apoptotic genes in the peri-infarct region were found.",
            "output": [
                "Does apelin-13 infusion salvage the peri-infarct region to preserve cardiac function after severe myocardial injury?"
            ]
        },
        {
            "id": "task847-af773e4f4bc440dba1143e0ba782bc30",
            "input": "Longer-term tuberculosis (TB) drug resistance surveillance among children is rare. We determined the prevalence of drug resistance among children with culture-confirmed TB from 2011 to 2013, compared these results with four previous consecutive 2-year periods and documented other mycobacterial isolates identified.', \"Surveillance study of mycobacterial culture in all children aged <13 years conducted from March 2011 to February 2013 at the Tygerberg Children's Hospital, Cape Town, South Africa. Drug susceptibility testing against isoniazid (INH) and rifampicin (RMP) was performed using line-probe assay (GenoType(\u00ae) MTBDRplus). Clinical data were obtained through folder review.\", 'Of 381 children, 323 (84.8%; 324 episodes) had Mycobacterium tuberculosis, 46 (12.1%) had M. bovis bacille Calmette-Gu\u00e9rin and 12 (3.1%) had non-tuberculous mycobacteria isolated. Forty-one (12.7%) children had M. tuberculosis resistant to INH and/or RMP; 15 (4.7%) had multidrug-resistant TB (MDR-TB). The prevalence of INH mono- or polyresistance remained stable; however, RMP monoresistance increased (0/313 in 2003-2005 vs. 6/324, 1.9%, in 2011-2013; P = 0.041); MDR-TB prevalence has declined significantly, from 26/292 (8.9%) in 2007-2009 to 15/324 (4.7%) in 2011-2013 (OR 0.50, 95%CI 0.24-0.99). The prevalence of human immunodeficiency virus co-infection has decreased significantly, from a peak of 29% to 15.3%.",
            "output": [
                "Does surveillance provide insight into epidemiology and spectrum of culture-confirmed mycobacterial disease in children?"
            ]
        },
        {
            "id": "task847-9f9f8ea220f348da8536a0b4cb45043c",
            "input": "To clarify the effect of human umbilical cord-derived mesenchymal stem cell (hUC-MSCs) treatment on colitis and to explore the role of CD5(+) B cells in MSC therapy.', 'The trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model was used. HUC-MSCs were transferred peritoneally. Survival rates, colitis symptoms, and macroscopic and histologic scores were evaluated. CD4(+) T helper (Th) cell subgroups and CD5(+) regulatory B cell (Bregs) in lymphocytes were quantitated by flow cytometry. Cytokine levels were detected by ELISA and Bio-plex. CD5(+) B cells were isolated for in vitro co-culture and adaptive transfer.', 'HUC-MSC treatment alleviated TNBS-induced colitis by increasing survival rates, relieving symptoms, and improving macroscopic and histologic scores. Labeled hUC-MSCs were located in the inflamed areas of colitis mice. Increases in regulatory T cells (Tregs) and CD5(+) B cells and decreases in Th1 cells, Th17 cells, and several pro-inflammatory cytokines were observed with hUC-MSC treatment. After adaptive transfer, CD5(+) B cells, which were located mainly in the peritoneal lavage fluid, improved TNBS-induced colitis by correcting Treg/Th1/Th17 imbalances. CD5(+) B cells also inhibited T-cell proliferation and produced interleukin (IL)-10.",
            "output": [
                "Do human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5 ( + ) B regulatory cells?"
            ]
        },
        {
            "id": "task847-e39f0ecc5ca141a398c37e871b75e0a9",
            "input": "The nucleus accumbens shell is a key brain area mediating the reinforcing effects of ethanol (EtOH). Previously, it has been shown that the density of \u03bc-opioid receptors in the nucleus accumbens shell is higher in alcohol-preferring Alko Alcohol (AA) rats than in alcohol-avoiding Alko Non-Alcohol rats. In addition, EtOH releases opioid peptides in the nucleus accumbens and opioid receptor antagonists are able to modify EtOH intake, all suggesting an opioidergic mechanism in the control of EtOH consumption. As the exact mechanisms of opioidergic involvement remains to be elucidated, the aim of this study was to clarify the role of accumbal \u03bc- and \u03ba-opioid receptors in controlling EtOH intake in alcohol-preferring AA rats.', 'Microinfusions of the \u03bc-opioid receptor antagonist CTOP (0.3 and 1\\xa0\u03bcg/site), \u03bc-opioid receptor agonist DAMGO (0.03 and 0.1\\xa0\u03bcg/site), nonselective opioid receptor agonist morphine (30\\xa0\u03bcg/site), and \u03ba-opioid receptor agonist U50488H (0.3 and 1\\xa0\u03bcg/site) were administered via bilateral guide cannulas into the nucleus accumbens shell of AA rats that voluntarily consumed 10% EtOH solution in an intermittent, time-restricted (90-minute) 2-bottle choice access paradigm.', 'CTOP (1\\xa0\u03bcg/site) significantly increased EtOH intake. Conversely, DAMGO resulted in a decreasing trend in EtOH intake. Neither morphine nor U50488H had any effect on EtOH intake in the used paradigm.",
            "output": [
                "Do accumbal \u03bc-Opioid Receptors Modulate Ethanol Intake in Alcohol-Preferring Alko Alcohol Rats?"
            ]
        },
        {
            "id": "task847-da68c87a07e44061b7806ced75536605",
            "input": "Contaminated hospital surfaces are an important source of nosocomial infections. A major obstacle in marketing antimicrobial surfaces is a lack of efficacy data based on standardized testing protocols.', 'We compared the efficacy of multiple testing protocols against several \"antimicrobial\" film surfaces.', 'Four clinical isolates were used: one Escherichia coli, one Klebsiella pneumoniae, and two Staphylococcus aureus strains. Two industry methods (modified ISO 22196 and ASTM E2149), a \"dried droplet\", and a \"transfer\" method were tested against two commercially available antimicrobial films, one film in development, an untreated control, and a positive (silver) control film. At 2 (only ISO) and 24 hours following inoculation, bacteria were collected from film surfaces and enumerated.', 'Compared to untreated films in all protocols, there were no significant differences in recovery on either commercial brand at 2 or 24 hours after inoculation. The silver surface demonstrated significant microbicidal activity (mean loss 4.9 Log10 CFU/ml) in all methods and time points with the exception of 2 hours in the ISO protocol and the transfer method. Using our novel droplet method, no differences between placebo and active surfaces were detected. The surface in development demonstrated variable activity depending on method, organism, and time point. The ISO demonstrated minimal activity at 2 hours but significant activity at 24 hours (mean 4.5 Log10 CFU/ml difference versus placebo). The ASTEM protocol exhibited significant differences in recovery of staphylococci (mean 5 Log10 CFU/ml) but not Gram-negative isolates (10 fold decrease). Minimal activity was observed with this film in the transfer method.",
            "output": [
                "Does the Activity of Antimicrobial Surfaces vary by Testing Protocol Utilized?"
            ]
        },
        {
            "id": "task847-57dfea211db9462f9f213bde3574cc62",
            "input": "To reduce cholangitis after pancreaticoduodenectomy (PD), we perform 'hepaticoplasty', in which the left side of the bile duct is cut to widen the diameter of the bile duct wall before hepaticojejunostomy. The aim of this study was to clarify the usefulness of hepaticoplasty to reduce cholangitis after PD.\", 'From January 2002 through December 2010, 161 patients underwent PD and were enrolled in this study. Patient demographics, surgical factors, and clinical and biochemical parameters were evaluated to examine the factors predictive of cholangitis after PD and confirm the usefulness of hepaticoplasty.', 'Cholangitis after PD occurred in 13 patients (8.1%). Multivariate analysis revealed that the ratio of the postoperative bile duct diameter to that before surgery was the only independent risk factor for cholangitis after PD (p\\xa0=\\xa00.0012). In the small bile duct group, in which the diameter was \u226415\\xa0mm before surgery (n\\xa0=\\xa099), hepaticoplasty reduced the narrowing of the bile duct after PD, and no cholangitis occurred. There were no complications related to hepaticoplasty.",
            "output": [
                "Does hepaticoplasty prevent cholangitis after pancreaticoduodenectomy in patients with small bile ducts?"
            ]
        },
        {
            "id": "task847-2ead26213bfd45f78184677a73854ab1",
            "input": "The Bacillus anthracis S-layer protein, BslA, plays a crucial role in mammalian infection. BslA is required to mediate adherence between host cells and vegetative forms of bacteria and this interaction promotes target organs adherence and blood-brain barrier (BBB) penetration in vivo. This study attempts to identify the potential eukaryotic ligand(s) for B. anthracis BslA protein.', 'Biochemical approaches have indicated that the putative host cell ligand(s) for BslA is a surface protein, which is independent of the sugar components for binding to Bs1A. A ligand screening using blot overlays, far Western blots and mass spectrometry analyses revealed that BslA binds to mammalian laminin. ELISA based solid-phase binding assays and surface plasmon resonance assays demonstrated that there were high affinity interactions between BslA(260-652) and laminin. The SPR results also revealed the dissociation constants values of 3.172\\u2009\u00d7\\u200910(-9)M for the binding of BslA(260-652) to laminin.",
            "output": [
                "Does bacillus anthracis S-layer protein BslA bound to extracellular matrix by interacting with laminin?"
            ]
        },
        {
            "id": "task847-23ee784e8b0946bbb6b95d8484aa6614",
            "input": "The aim of this review is to discuss the possibilities and disadvantages of the techniques for visual inspection of the uterine cervix with acetic acid (VIA) and with Lugol's iodine (VILI) for early detection of cervical neoplasia. Efficient cervical screening method, approved in practice, is cytology--PAP smear. The lack of organized screening program in Bulgaria is the reason why a lot of cases of cervical cancer are missed or diagnosed late. This raises the question for searching alternative tests to assess the uterine cervix that do not use special techniques and have a reasonable cost. Published results show that VIA and VILI represent an appropriate alternative for cervical screening. The results of VIA and VILI are immediately available and do not require any laboratory processing.",
            "output": [
                "Does [ be THERE A PLACE FOR VIA AND VILI IN OUR PRACTICE ]?"
            ]
        },
        {
            "id": "task847-4eb448c71f564b2dbafb42406bb8eb80",
            "input": "Patient selection for endovascular revascularization treatment (ERT) in acute ischemic stroke depends on the expected benefit-risk ratio. As rapid revascularization is a major determinant of good functional outcome, we aimed to identify its predictors after ERT.', 'Consecutive stroke patients from a single stroke center with distal internal carotid artery-, proximal middle cerebral artery- or T-occlusions treated with ERT were retrospectively selected. We assessed admission noncontrast computed tomography and computed tomography angiography for thrombus location, thrombus load (clot burden score), and collateral status. Clinical data were extracted from medical charts. Univariate and multivariate regression analyses were performed to identify predictors of revascularization (thrombolysis in cerebral infarction \u22652b) after ERT.', 'A total of 63 patients were identified (median age, 73 years; interquartile range: 62-77; 40 females). Sixteen patients (25.4%) underwent intravenous thrombolysis (ivT) before ERT. Twenty-two patients (34.9%) had additional intra-arterial application of recombinant tissue plasminogen activator. The overall recanalization rate was 66.7%, and 9.5% had symptomatic intracranial bleeding. In-hospital mortality was 15%, and 30% reached good functional outcome at discharge. In the univariate analysis, preceding ivT and the number of passes for thrombectomy (dichotomized \u22642 versus >2) were associated with recanalization. There was a trend for number of thrombectomy passes (as continuous variable) and multimodal ERT. In the multivariate regression analysis, ivT prior to ERT and passes of thrombectomy were identified as independent predictors for recanalization.",
            "output": [
                "Does intravenous Thrombolysis and pass of Thrombectomy as Predictors for Endovascular Revascularization in Ischemic Stroke?"
            ]
        },
        {
            "id": "task847-223350f8c33a4f949831c96b2d95aa1f",
            "input": "Iron deficiency (ID) anemia leads to long-term neurodevelopmental deficits by altering iron-dependent brain metabolism. The objective of the study was to determine if ID induces metabolomic abnormalities in the cerebrospinal fluid (CSF) in the pre-anemic stage and to ascertain the aspects of abnormal brain metabolism affected.', 'Standard hematological parameters [hemoglobin (Hgb), mean corpuscular volume (MCV), transferrin (Tf) saturation, and zinc protoporphyrin/heme (ZnPP/H)] were compared at 2, 4, 6, 8, and 12 months in iron-sufficient (IS; n\\u2009=\\u20097) and iron-deficient (ID; n\\u2009=\\u20097) infant rhesus monkeys. Five CSF metabolite ratios were determined at 4, 8, and 12 months using ', 'ID infants developed ID (Tf saturation\\u2009<\\u200925%) by 4 months of age and all became anemic (Hgb\\u2009<\\u2009110\\u2005g/L and MCV\\u2009<\\u200960\\u2005fL) at 6 months. Their heme indices normalized by 12 months. Pyruvate/glutamine and phosphocreatine/creatine (PCr/Cr) ratios in CSF were lower in the ID infants by 4 months (P\\u2009<\\u20090.05). The PCr/Cr ratio remained lower at 8 months (P\\u2009=\\u20090.02). ZnPP/H, an established blood marker of pre-anemic ID, was positively correlated with the CSF citrate/glutamine ratio (marginal correlation, 0.34; P\\u2009<\\u20090.001; family wise error rate\\u2009=\\u20090.001).",
            "output": [
                "Does metabolomic analysis of CSF indicate brain metabolic impairment precedes hematological indices of anemia in the iron-deficient infant monkey?"
            ]
        },
        {
            "id": "task847-83a91dc8f67c4b8fbc4dc27e9018c42f",
            "input": "Alterations in phenotype and function of endothelial progenitor cells (EPCs) have been associated with poor vascular outcomes and impaired vascular repair in various conditions. Our hypothesis was that patients with PM and DM have dysregulation of EPCs driven by type I IFN and IL-18 similar to other autoimmune diseases.', 'Quantification of circulating EPCs was performed by flow cytometry in patients with PM/DM and matched healthy controls. The ability of EPCs to differentiate into mature endothelial cells was investigated by light and fluorescence microscopy quantification in the presence or absence of PM/DM or control serum, neutralizing antibodies to type I IFN receptor or IL-18. Serum type I IFN activity was quantified by induction of type I IFN-inducible genes in HeLa cells. Circulating IL-18 concentrations were assessed by ELISA.', 'Circulating EPCs were significantly lower in PM/DM patients compared with controls. PM/DM EPCs displayed a decreased capacity to differentiate into mature endothelial cells and PM/DM serum significantly inhibited differentiation of control EPCs. This effect was reversed in the majority of samples with neutralizing antibodies to IL-18 or to type I IFN receptor or by a combination of these antibodies. Patients with associated impairments in EPC function had higher type I IFN serum activity.",
            "output": [
                "Is dysfunction of endothelial progenitor cells associated with the type I IFN pathway in patients with polymyositis and dermatomyositis?"
            ]
        },
        {
            "id": "task847-329921495a84464a9629cf75dc6b67fe",
            "input": "Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8\\xa0wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention.', 'Volunteers were supplemented daily with 36\\xa0mg/kg body weight (BW) of GAA for the first 4\\xa0wk of the intervention; afterward GAA dosage was titrated \u226460\\xa0mg/kg BW of GAA daily. At baseline, 4, and 8\\xa0wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity.', 'Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4\\xa0wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P\\xa0<\\xa00.05). Thalamus creatine levels decreased after 4\\xa0wk for 6.5% (P\\xa0=\\xa00.02), and increased nonsignificantly after 8\\xa0wk for 8% (P\\xa0=\\xa00.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P\\xa0<\\xa00.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention.",
            "output": [
                "Does dietary guanidinoacetic acid increase brain creatine levels in healthy men?"
            ]
        },
        {
            "id": "task847-b754b0748b7e4299a737e9f607ee0235",
            "input": "Complement activation is considered a major mechanism in innate immunity. Although it is mainly involved in initiating inflammation, recent data reported its involvement in other processes such as tissue regeneration. In the dental pulp, complement C5a fragment has been shown to be involved in the recruitment of dental pulp stem cells (DPSCs). This study sought to investigate the possible role of C3a, another complement fragment, in the early steps of dentin-pulp regeneration.', 'Expression of C3a receptor (C3aR) was investigated by immunofluorescence and reverse transcriptase polymerase chain reaction on cultured pulp fibroblasts, STRO-1-sorted DPSCs, as well as on human tooth sections in\\xa0vivo. The effect of C3a on proliferation of both DPSCs and pulp fibroblasts was investigated by MTT assay. Cell migration under a C3a gradient was investigated by using microfluidic chemotaxis chambers.', 'C3aR was expressed in\\xa0vivo as well as in cultured pulp fibroblasts co-expressing fibroblast surface protein and in DPSCs co-expressing STRO-1. Addition of recombinant C3a induced a significant proliferation of both cell types. When subjected to a C3a gradient, DPSCs were mobilized but not specifically recruited, whereas pulp fibroblasts were specifically recruited following a C3a gradient.",
            "output": [
                "Does complement C3a mobilize Dental Pulp Stem Cells and Specifically Guides Pulp Fibroblast Recruitment?"
            ]
        },
        {
            "id": "task847-971b827f13b9464da3dece7b36d0a895",
            "input": "The aim of this study was to investigate the antiproliferative and cytotoxic effects of a newly synthesized molecule named paracetamol acetohydroxamic acid (PaCaHa) on human neoplastic cell lines.', 'A549, CRL 2923, HeLa, and ARPE were treated with various concentrations of PaCaHa and DMSO (vehicle control). The cytotoxic/cytostatic effects of PaCaHa were determined after a 24-h incubation period and compared to the DMSO control. The cytotoxic and antiproliferative effects were determined by the trypan blue dye exclusion and MTT methods.', 'A higher susceptibility to PaCaHA was found in CRL 2923 and HeLa cells, while A549 and ARPE cells were less responsive to PaCaHa. The percent of cytotoxicity resulting from 400 \u00b5g/mL of PaCaHa were >90 for CRL-2923 and HeLa, 68 for A549, and 64 for ARPE cells. The cytotoxic difference between CRL-2923/HeLa and ARPE/A549 cells was significant (P < 0.05).",
            "output": [
                "Does paCaHa inhibit proliferation of human cancer cells in vitro?"
            ]
        },
        {
            "id": "task847-a478a43302f947d98d4014e4e274d7a2",
            "input": "Erectile dysfunction (ED) and atherosclerotic cardiovascular disease (ASCVD) share many common risk factors, and vascular ED is a marker for increased ASCVD risk. Low 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with increased ASCVD risk, but less is known regarding the relationship of low 25(OH)D with ED. We determined whether 25(OH)D deficiency is associated with ED independent of ASCVD risk factors.', 'We performed cross-sectional analyses of 3390 men aged \u226520 years free of ASCVD who participated in NHANES 2001-2004. Serum 25(OH)D was measured by the DiaSorin radioimmunoassay; deficiency was defined as levels <20\\xa0ng/ml (<50\\xa0nmol/L). Self-reported ED, assessed by a single validated question, was defined as men who reported being \"never\" or \"sometimes able\" to maintain an erection. We assessed the relationship between 25(OH)D deficiency and ED prevalence using adjusted Poisson regression methods.', 'After accounting for NHANES sampling, the weighted prevalence of 25(OH)D deficiency and of ED were 30% and 15.2%, respectively. 25(OH)D levels were lower in men with vs. those without ED (mean 22.8 vs 24.3\\xa0ng/mL, respectively; p\\xa0=\\xa00.0005). After adjusting for lifestyle variables, comorbidities, and medication use, men with 25(OH)D deficiency had a higher prevalence of ED compared to those with levels \u226530\\xa0ng/ml (Prevalence Ratio 1.30, 95% CI 1.08-1.57).",
            "output": [
                "Is vitamin D deficiency independently associated with greater prevalence of erectile dysfunction : The National Health and Nutrition Examination Survey ( NHANES ) 2001-2004?"
            ]
        },
        {
            "id": "task847-3d70301bb22b4c20a509d80c48edefa1",
            "input": "Profiles of allergic sensitization are poorly documented in infancy. Relations between early sensitization and allergic morbidity need to be clarified.', 'This study dealt with children involved in the Pollution and Asthma Risk: an Infant Study (PARIS), a population-based prospective birth cohort. Allergic sensitization to twelve food and four inhalant allergens was assessed at 18\\xa0months and defined by a specific immunoglobulin E (IgE) level \u22650.35\\xa0kU', 'Sensitization to any allergen concerned 13.6% of infants. By cluster analysis, 1525 infants were grouped into three profiles: 89.2% not or rarely sensitized (only 3.7% of sensitized), 9.2% mainly sensitized to one or few allergens (45.2% of monosensitized and 45.9% of paucisensitized) and 1.6% all polysensitized. The prevalence of doctor-diagnosed asthma, rhinitis, eczema, food allergy and multimorbidity at 2\\xa0years increased from profile one to profile three (p-trend <0.001). At 6\\xa0years, symptoms of current asthma, rhinitis, eczema and multimorbidity were significantly more frequent in the last two profiles.",
            "output": [
                "Is early polysensitization associated with allergic multimorbidity in PARIS birth cohort infants?"
            ]
        },
        {
            "id": "task847-abd003683dda44c9985dba67f9044b9c",
            "input": "Irritancy levels of surfactants on human skin have not been clarified completely. The relationships between skin damage and changes of skin properties caused by various surfactants were investigated using non-invasive measurements.', 'Aqueous solutions of seven kinds of anionic, non-ionic, and amphoteric surfactants were exposed to the inside of forearm skin of 20 human subjects in two separate studies using the cup method. Hydration of the stratum corneum (SC), transepidermal water loss (TEWL), pH, skin surface roughness, and contents of the SC were measured before and after one exposure and after five and nine consecutive exposures to various surfactants. The discontinuation ratio of subjects for testing in each surfactant was determined by skin irritation symptoms and was defined as the degree of skin damage.', 'Significant changes were observed only in hydration, TEWL, and natural moisturizing factors (NMF) content in the SC following surfactant exposure. A significant correlation was observed between the discontinuation ratio of each surfactant and the changes of hydration, TEWL, and NMF. Especially, the change of SC hydration showed an excellent correlation with the discontinuation ratio both for single (r = 0.942, P < 0.001) and for chronic exposures (r = 0.934, P < 0.001).",
            "output": [
                "Are changes in hydration of the stratum corneum the most suitable indicator to evaluate the irritation of surfactants on the skin?"
            ]
        },
        {
            "id": "task847-0cd5c20959294131a4d4245d715a4271",
            "input": "Acute lymphoblastic leukemia (ALL) makes up a significant proportion of all pediatric cancers, and relapsed ALL is a leading cause of cancer-associated deaths in children. Identification of risk factors and druggable molecular targets in ALL can lead to a better stratification of treatments and subsequent improvement in prognosis.', \"We enrolled 59 children with relapsed or primary refractory ALL who were treated in our institutions. We primarily performed RNA sequencing (RNA-seq) using patients' leukemic cells to comprehensively detect gene fusions and analyze gene expression profiles. On the basis of results obtained by RNA-seq, we performed genetic validation, functional analysis, and in vitro drug sensitivity testing using patients' samples and an exogenous expression model.\", 'We identified a total of 26 gene fusions in 22 patients by RNA-seq. Among these, 19 were nonrandom gene fusions already described in ALL, and four of the remaining seven involved identical combination of MEF2D and BCL9. All MEF2D-BCL9-positive patients had B-cell precursor immunophenotype and were characterized as being older in age, being resistant to chemotherapy, having very early relapse, and having leukemic blasts that mimic morphologically mature B-cell leukemia with markedly high expression of HDAC9. Exogenous expression of MEF2D-BCL9 in a B-cell precursor ALL cell line promoted cell growth, increased HDAC9 expression, and induced resistance to dexamethasone. Using a primary culture of leukemic blasts from a patient, we identified several molecular targeted drugs that conferred inhibitory effects in vitro.",
            "output": [
                "Does mEF2D-BCL9 Fusion Gene be Associated With High-Risk Acute B-Cell Precursor Lymphoblastic Leukemia in Adolescents?"
            ]
        },
        {
            "id": "task847-3ef438a1b6a54af7981ad01dda6287a7",
            "input": "The natural product tetramethylpyrazine (TMP) and resveratrol have a variety of biologic activities, including anti-cancer effects. However the pharmacological function of CSTMP (a newly designed and synthesized TMP and resveratrol derivative) in cancer have not been elucidated.', 'In RPMI8226 cells, the cytotoxic effects and apoptosis were detected by MTT and Double staining for Annexin V-FITC and propidium iodide (PI). The protein and mRNA expression levels were detected by Real Time PCR and Western blot, respectively. The localization of cleaved caspase-12 was evaluated by immunofluorescent staining. The activation of caspase were measured by colorimetric assays and Western blot.', 'CSTMP showed significantly cytotoxic effects and induced apoptosis in RPMI8226 cells. Caspase activation, Cytochrome c release and Bax, Bcl-2 and Bcl-XL levels analyses demonstrated that the anti-cancer effect of CSTMP in RPMI8226 cells was mediated by promoting caspase- and mitochondria-dependent apoptosis. In addition, CSTMP induced the increased expression of endoplasmic reticulum (ER) stress related proteins (CHOP, GRP78, GRP94 and cleaved caspase-12) and the activation of multiple branches of ER stress transducers (PERK-eIF2\u03b1, IRE1\u03b1 and ATF6). Moreover, knockdown of CHOP by siRNA markedly inhibited CSTMP-induced cytotoxic effects, caspases activity and mitochondrial dysfunction in RPMI8226 cells.",
            "output": [
                "Does cSTMP induce apoptosis and mitochondrial dysfunction in human myeloma RPMI8226 cells via CHOP-dependent endoplasmic reticulum stress?"
            ]
        },
        {
            "id": "task847-1c69d99e3c414532bb7c3dc18b10cf04",
            "input": "Septic hip revisions are associated with greater complications and higher costs than aseptic revisions. It is unclear whether blood loss and transfusion requirements are different in septic and aseptic revisions. We hypothesized that the blood loss and transfusion are dependent on the complexity of the revision surgery and patient's general health rather than the presence of infection.\", 'We retrospectively reviewed 626 revision total hip arthroplasties in 547 patients between 2009 and 2013. All the procedures were classified as septic (n\\xa0= 120) or aseptic (n\\xa0= 506) based on the Musculoskeletal Infection Society criteria for periprosthetic joint infection. Independent risk factors for transfusion and blood loss were analyzed using a multiple regression analysis.', 'The transfusion rate was higher in septic revisions (septic\\xa0= 108/120 [90%], aseptic\\xa0= 370/506 [73%]; P < .001), so was the average amount of blood loss (septic\\xa0= 2533 \u00b1 161 mL, aseptic\\xa0= 1974 \u00b1 68 mL; P < .001). After adjusting for potential confounders, infection was not an independent risk factor for transfusion (P = .176) or blood loss (P = .437). Increasing age (P = .004), higher American Society of Anesthesiologists score (P = .047), lower preoperative hemoglobin (P < .001), cell saver use (P < .001), and complex revision surgery (P < .001) were independently associated with greater risk of transfusion.",
            "output": [
                "Is infection a Risk Factor for Perioperative and Postoperative Blood Loss and Transfusion in Revision Total Hip Arthroplasty?"
            ]
        },
        {
            "id": "task847-f5343180272f4c56ae3bf50329a94cc9",
            "input": "We have previously shown that advanced glycation-endproducts (AGEs) induced NF\u03baB activation in differentiated mouse podocytes. This NF\u03baB activation may contribute to the progression of renal disease and mediation of fibrosis by various mechanisms. This study was undertaken to test whether this detrimental response may be reversed by vitamin D3 or its analogue paricalcitol.', 'Differentiated mouse podocytes were challenged with glycated bovine serum albumin (AGE-BSA), or non-glycated control BSA (in the presence or absence of various concentrations of vitamin D3 (decostriol, 1\u03b1,25-dihydroxyvitamin D3)) or its active analog paricalcitol. Quantitative mRNA expressions were measured by real-time PCR, whereas protein expressions were determined by Western blotting followed by densitometry. Cytoplasmic and nuclear protein expression of the NF\u03baB subunit p65 (Rel A) were determined by Western blotting. Furthermore, the ratio of phosphorylated to non-phosphorylated I\u03baB-\u03b1 was measured using specific antibodies. Electrophoretic mobility shift assays and a capture ELISA assay were used to assess NF\u03baB transactivation in vitro. In addition, NF\u03baB transactivation was also monitored in HEK-NF\u03baBIA reporter cells using live cell luminometry.', 'Podocytes expressed the receptor for vitamin D. The vitamins did not suppress receptor for AGEs (RAGE) expression; instead, they rather upregulated RAGE. Although vitamin D3 and paricalcitol partly and differentially modified some of the studied parameters, both hormones inhibited AGE-BSA-induced NF\u03baB transactivation, presumably by various mechanisms including the upregulation of I\u03baB-\u03b1 protein, keeping NF\u03baB sequestered in an inactive state in the cytoplasm.",
            "output": [
                "Does vitamin D3 Partly antagonize Advanced-Glycation Endproducts-Induced NF\u03baB Activation in Mouse Podocytes?"
            ]
        },
        {
            "id": "task847-de757dcb81ba4fa29e42d4d13b9adb4f",
            "input": "The greater omentum has been found to be immunologically competent in protecting abdominal organs from inflammation. Anastomotic omentoplasty has been used and proven effective in preventing anastomotic leaks after an esophagectomy. However, pulmonary complications are still a substantial problem after an esophagectomy. This study investigated the benefits of mediastinal transposition of the omentum, a modification of the conventional omental wrapping technique, in controlling overall postoperative intrathoracic complications.', \"From January 2010 to March 2015, 208 consecutive patients receiving an open Ivor-Lewis esophagectomy at our institution were retrospectively reviewed. One hundred twenty-one patients with omentum mediastinal transposition were assigned to the transposition group and 87 patients without omental transposition were placed in the non-transposition group. The patients' demographics, postoperative short-term outcomes, and in-hospital cost were documented and analyzed.\", 'Mediastinal transposition of the omentum led to a shorter postoperative hospital stay (14 vs. 16 d, P=0.038) and a lower intrathoracic infection rate (30.6% vs. 48.3%, P=0.009). Intrathoracic infection was milder in the transposition group (P=0.005), though a non-significant was found in overall complications (P=0.071). The multivariate logistic regression analyses identified omentum mediastinal transposition (P=0.007, OR=0.415) as an independent protective factor for postoperative intrathoracic infection. The total in-hospital cost was comparable in both groups (P>0.05), whereas the pharmacy cost was lower in the transposition group than in the non-transposition group (\u00a521,668 vs. \u00a527,012, P=0.010).",
            "output": [
                "Does mediastinal transposition of the omentum reduce infection severity and pharmacy cost for patients undergoing esophagectomy?"
            ]
        },
        {
            "id": "task847-5a058f3243494920bfabecfba3e03e32",
            "input": "To assess the prognostic value of coronary CT angiography (CTA) for prediction of major adverse cardiac events (MACE) over a long-term follow-up period.', 'A total of 1469 low-to-intermediate-risk patients (65.9 years; 44.2% females) were included in our prospective cohort study. CTA was evaluated for (i) stenosis severity (minimal <10%; mild <50%; moderate 50-70%; severe >70%), (ii) plaque types (calcified, mixed dominantly calcified, mixed dominantly non-calcified, non-calcified), and (iii) high-risk plaque criteria [low-attenuation plaque (LAP) quantified by HU, napkin-ring (NR) sign, spotty calcification <3 mm, and remodelling index (RI)]. Over a follow-up of mean 7.8 years, MACE rate was 41 (2.8%) and 0% in patients with negative CTA. MACE rate increased along with stenosis severity by CTA (from 1.3 to 7.8%) (P < 0.001) and was higher in T3/T4 plaques than in T2/T1 (7.8 vs. 1.9%; P < 0.0001). LAP density was lower (35.2 HU \u00b1 32 vs. 108.8 HU \u00b1 53) (P < 0.001) and both NR-sign prevalence with n = 26 (63.4%) vs. n = 40 (28%) and LAP <30, <60, and <90 HU prevalence with 46.3-78% vs. 2.4-7% were higher in the MACE group (P < 0.001). On univariate and unadjusted multivariable proportional Hazards model, LAP <60 HU and NR were the strongest MACE predictors (HR 4.96; 95% CI: 2.0-12.2 and HR 3.85; 95% CI: 1.7-8.6) (P < 0.0001), while spotty calcification (HR 2.2; 95% CI: 1.1-4.3, P < 0.001), stenosis severity, and plaque type (HR 1.5; 95% CI: 1.1-2.3 and HR 1.7; 95% CI: 1.1-2.6) (P < 0.001) were less powerful. After adjusting for risk factors, CTA stenosis severity, and plaque type, LAP <60 HU and the NR sign remained significant (P < 0.001), while the effect of NR sign was even enhancing. HRP criteria were independent predictors from other risk factors.",
            "output": [
                "Are the high-risk criteria low-attenuation plaque < 60 HU and the napkin-ring sign the most powerful predictors of MACE : a long-term follow-up study?"
            ]
        },
        {
            "id": "task847-f7c7ea0c376d430c95c6b9d5ef714b99",
            "input": "IL-17A is a key driver of human autoimmune diseases, particularly psoriasis.', 'We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A-driven pathology.', 'We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti-IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases.', 'IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P\\xa0<\\xa0.001). Proteomic and gene transcription analyses revealed dysregulated antimicrobial peptides, proinflammatory cytokines, and neutrophil chemoattractants, levels of which returned to normal after treatment with secukinumab. \u03b2-Defensin 2 (BD-2) was identified as a biomarker of IL-17A-driven pathology by comparing protein expression in patients with psoriasis versus that in healthy subjects (5746 vs 82 pg/mL in serum, P\\xa0<\\xa0.0001; 2747 vs\\xa0<218 pg/mL in dermis, P\\xa0<\\xa0.001), responsiveness to secukinumab therapy, and synergistic induction by IL-17A and TNF-\u03b1 in epidermal keratinocytes. In a validation set of sera from 601 patients with autoimmune diseases thought to be IL-17A driven, we found that BD-2 levels are most highly increased in patients with psoriatic skin lesions, and in patients with psoriasis, BD-2 levels correlated well with IL-17A levels (r\\xa0=\\xa00.70, n\\xa0=\\xa0199, P\\xa0<\\xa0.001) and Psoriasis Area and Severity Index scores (r\\xa0=\\xa00.53, n\\xa0=\\xa0281, P\\xa0<\\xa0.001).",
            "output": [
                "Is \u03b2-Defensin 2 a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis?"
            ]
        },
        {
            "id": "task847-bb35cfbfa2594bcd9b84336d35de0fd8",
            "input": "Perturbation of the endoplasmic reticulum (ER) homeostasis has emerged as one of the prominent features of obesity and diabetes. This occurs when the adaptive unfolded protein response (UPR) fails to restore ER function in key metabolic tissues. We previously reported increased inflammation and impaired heat shock response (HSR) in obese human subjects that were restored by physical exercise. Here, we investigated the status of ER stress chaperone; glucose-regulated protein 78 (GRP78) and its downstream UPR pathways in human obese, and their modulation by a supervised 3-month physical exercise.', \"Subcutaneous adipose tissue (SAT) and blood samples were collected from non-diabetic adult human lean (n=40) and obese (n=40, at baseline and after 3months of physical exercise). Transcriptomic profiling was used as a primary screen to identify differentially expressed genes and it was carried out on SAT samples using the UPR RT(2) Profiler PCR Array. Conventional RT-PCR, immunohistochemistry, immunofluorescence, Western blot and ELISA were used to validate the transcriptomic data. Correlation analyses with the physical, clinical and biochemical outcomes were performed using Pearson's rank correlation coefficient.\", 'Levels of GRP78 and its three downstream UPR arms; activating transcription factor-6 (ATF6), inositol-requiring enzyme-1\u03b1 (IRE1\u03b1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were increased in obese subjects. More interestingly, higher levels of circulating GRP78 protein were found in obese compared to lean subjects which correlated negatively with maximum oxygen uptake (VO2 Max) but positively with high-sensitivity C-reactive protein (hsCRP) and obesity indicators such as BMI, percentage body fat (PBF) and waist circumference. GRP78 increased secretion in obese was further confirmed in vitro using 3T3-L1 preadipocyte cells under ER stress. Finally, we showed that physical exercise significantly attenuated the expression and release of GRP78 with a concomitant reduction in the phosphorylation of IRE1\u03b1 and eukaryotic initiation factor-2\u03b1 (eIF2\u03b1).",
            "output": [
                "Does physical exercise alleviate ER stress in obese humans through reduction in the expression and release of GRP78 chaperone?"
            ]
        },
        {
            "id": "task847-7a9621774f564a61ae5b00bc1f2fbe58",
            "input": "Sugar intake has been associated with an increased prevalence of obesity, other noncommunicable diseases, and dental caries. The WHO recommends that free sugars should be <10% of total energy intake (TEI) and that additional health benefits could be obtained with a reduction below 5% of TEI.', 'The objective of this study was to estimate the total, intrinsic, and added sugar intake in the Mexican diet and to identify the food groups that are the main sources of these sugars.', 'We used data from a national probabilistic survey [ENSANUT (National Health and Nutrition Survey) 2012], which represents 3 geographic regions and urban and rural areas. Dietary information was obtained by administering a 24-h recall questionnaire to 10,096 participants. Total sugar intake was estimated by using the National Institute of Public Health (INSP) food-composition table and an established method to estimate added sugars.', 'The mean intakes of total, intrinsic, and added sugars were 365, 127, and 238 kcal/d, respectively. Added sugars contributed 13% of TEI. Sugar-sweetened beverages (SSBs) were the main source of sugars, contributing 69% of added sugars. Food products high in saturated fat and/or added sugar (HSFAS) were the second main sources of added sugars, contributing 25% of added sugars.",
            "output": [
                "Do sugar-Sweetened Beverages Are the Main Sources of Added Sugar Intake in the Mexican Population?"
            ]
        },
        {
            "id": "task847-2680c7afabe1451894b5678f608b6573",
            "input": "The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer.', 'We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-, 2-, 3-, and 5-year survival rate), response rate of chemotherapy, radical resection rate, post-operative complication rate, and adverse effects of chemotherapy.', 'Five randomized controlled trials and six clinical controlled trials involving 1,240 patients were eligible for analysis. Compared with the adjuvant chemotherapy group, the perioperative chemotherapy group had significantly better prognosis (HR, 0.74; 95\\xa0% CI, 0.61 to 0.89; P\\u2009<\\u20090.01). The difference between the two groups remained significant in the studies that used combination chemotherapy as the neoadjuvant chemotherapy regimen (HR, 0.59; 95\\xa0% CI, 0.46 to 0.76; P\\u2009<\\u20090.01) but were not significant in the studies that used fluoropyrimidine monotherapy (HR, 0.93; 95\\xa0% CI, 0.56 to 1.55; P\\u2009=\\u20090.84). Furthermore, the two groups showed no significant differences in the post-operative complication rates (relative risk, 0.98; 95\\xa0% CI, 0.63 to 1.51; P\\u2009=\\u20090.91) or adverse effects of chemotherapy (P\\u2009>\\u20090.05 for all adverse effects).",
            "output": [
                "Is which better for gastric cancer patients , perioperative or adjuvant chemotherapy : a meta-analysis?"
            ]
        },
        {
            "id": "task847-a3282d77c23a46f3a7462b8f664b14e6",
            "input": "The lumbar facet capsular ligament (FCL) is a posterior spinal ligament with a complex structure and kinematic profile. The FCL has a curved geometry, multiple attachment sites, and preferentially aligned collagen fiber bundles on the posterior surface that are innervated with mechanoreceptive nerve endings. Spinal flexion induces three-dimensional (3D) deformations, requiring the FCL to maintain significant tensile and shear loads. Previous works aimed to study 3D facet joint kinematics during flexion, but to our knowledge none have reported localized FCL surface deformations likely created by this complex structure.', 'The purpose of this study was to elucidate local deformations of both the posterior and anterior surfaces of the lumbar FCL to understand the distribution and magnitude of in-plane and through-plane deformations, including the prevalence of shear.', 'The FCL anterior and posterior surface deformations were quantified through creation of a finite element model simulating facet joint flexion using a realistic geometry, physiological kinematics, and fitted constitutive material.', 'Geometry was obtained from the micro-CT data of a healthy L3-L4 facet joint capsule (n=1); kinematics were extracted from sagittal plane fluoroscopic data of healthy volunteers (n=10) performing flexion; and average material properties were determined from planar biaxial extension tests of L4-L5 FCLs (n=6). All analyses were performed with the non-linear finite element solver, FEBio. A grid of equally spaced 3\u00d73 nodes on the posterior surface identified regional differences within the strain fields and was used to create comparisons against previously published experimental data. This study was funded by the National Institutes of Health and the authors have no disclosures.', 'Inhomogeneous in-plane and through-plane shear deformations were prominent through the middle body of the FCL on both surfaces. Anterior surface deformations were more pronounced because of the small width of the joint space, whereas posterior surface deformations were more diffuse because the larger area increased deformability. We speculate these areas of large deformation may provide this proprioceptive system with an excellent measure of spinal motion.",
            "output": [
                "Does computer simulation of lumbar flexion show shear of the facet capsular ligament?"
            ]
        },
        {
            "id": "task847-2244e9d13265412886a6b97a349e7650",
            "input": "Histone deacetylase (HDAC) inhibitors have been reported to improve essential and secondary hypertension. However, the specific HDAC that might serve as a therapeutic target and the associated upstream and downstream molecules involved in regulating hypertension remain unknown. Our study was aimed at investigating whether a selective inhibitor of class II HDAC (MC1568) modulates hypertension, elucidating the underlying mechanism.', 'Hypertension was established by administering angiotensin II (Ang II) to mice before treatment with MC1568. SBP was measured.', \"Treatment with MC1568 reduced elevated SBP; attenuated arterial remodeling in the kidney's small arteries and thoracic aorta; and inhibited cell cycle regulatory gene expression, vascular smooth muscle cell (VSMC) proliferation, DNA synthesis, and VSMC hypertrophy in vivo and in vitro. Ang II enhanced the expression of phosphorylated HDAC4 and GATA-binding factor 6 (GATA6) proteins, which were specifically localized in the cytoplasm of cells in the arteries of kidneys and in aortas. Forced expression and knockdown of HDAC4 increased and decreased, respectively, the proliferation and expression of cell cycle genes in VSMCs. GATA6, a newly described binding partner of HDAC4, markedly enhanced the size and number of VSMCs. Calcium/calmodulin-dependent kinase II\u03b1 (CaMKII\u03b1), but not HDAC4, translocated from the nucleus to the cytoplasm in response to Ang II. CaMKII\u03b1 and protein kinase D1 were associated with VSMC hypertrophy and hyperplasia via direct interaction with HDAC4. MC1568 treatment weakened the association between HDAC4 and CaMKII\u03b1.",
            "output": [
                "Do histone deacetylase and GATA-binding factor 6 regulate arterial remodeling in angiotensin II-induced hypertension?"
            ]
        },
        {
            "id": "task847-f7b33d4a17c6494bb690ff9d1010ebcd",
            "input": "Aujeszky's disease (AD) is an economically important disease affecting both wild and domestic pigs of the species Sus scrofa. A previous study yielded serological evidence of AD in Korean wild boars, which could spread AD to other animals. A new Aujeszky's disease virus (ADV) bait vaccine is required to prevent AD outbreaks in swine. In the present study, we investigated the safety and immunogenicity of a gE-deleted marker vaccine, strain YS-400, in young domestic pigs.\", 'The YS-400 strain was propagated in Vero cells, and the trial ADV bait vaccine (a vaccine blister in a matrix including an attractant) was prepared. Pigs were orally immunized with the vaccine (2 mL, 10(7.5) TCID50/mL) delivered using a syringe or in the bait vaccine. The animals were observed for 9 weeks after vaccination, and immunogenicity was assessed using a virus neutralization (VN) test and enzyme linked immunosorbent assay.', 'The YS-400 strain was non-pathogenic to pigs when given orally and induced high VN titers (1:32-1:128) 6 weeks post-administration. Of the pigs given the ADV bait vaccine twice or three times, 40% were seropositive by 2 weeks, and 100% were seropositive by 7 weeks after the first dose. Pigs that consumed the AD bait vaccine three times developed VN titers that were slightly higher than those of pigs given the vaccine twice.",
            "output": [
                "Does an oral Aujeszky 's disease vaccine ( YS-400 ) induce neutralizing antibody in pigs?"
            ]
        },
        {
            "id": "task847-f088dc19e2ec4eefb4b7106add6b5754",
            "input": "One of the most important tools against foot-and-mouth disease, a highly contagious and variable viral disease of cloven-hoofed animals, is vaccination. However, the effectiveness of foot-and-mouth disease vaccines on slowing the spread of the disease is questionable. In contrast, high potency vaccines providing early protection may solve issues with the spread of the disease, escaping mutants, and persistency. To increase the potency of the vaccine, additives such as saponin and aluminium hydroxide are used. However, the use of saponin with an oil adjuvant is not common and is sometimes linked to toxicity. QS-21, which is less toxic than Quil A, has been presented as an alternative for use with saponin. In this study, the addition of QS-21 to a commercially available foot-and-mouth disease water-in-oil-in-water emulsion vaccine was evaluated in cattle.', 'After vaccination, serum samples were collected periodically over 3 months. Sera of the QS-21 and normal oil vaccine groups were compared via serum virus neutralization antibody titre and liquid phase blocking enzyme-linked immunosorbent assay antibody titre.', 'The results showed that there was a significant early antibody increase in the QS-21 group.",
            "output": [
                "Does qS-21 enhance the early antibody response to oil adjuvant foot-and-mouth disease vaccine in cattle?"
            ]
        },
        {
            "id": "task847-5f1b09cd65dd43b0b62747ee27730ce5",
            "input": "Sacral nerve stimulation is proposed as a treatment for slow-transit constipation. However, in our randomized controlled trial we found no therapeutic benefit over sham stimulation. These patients have now been followed-up over a long-term period.', 'The purpose of this study was to assess the long-term efficacy of sacral nerve stimulation in patients with scintigraphically confirmed slow-transit constipation.', 'This study was designed for long-term follow-up of patients after completion of a randomized controlled trial.', 'It was conducted at an academic tertiary public hospital in Sydney.', 'Adults with slow-transit constipation were included.', 'At the 1- and 2-year postrandomized controlled trial, the primary treatment outcome measure was the proportion of patients who reported a feeling of complete evacuation on >2 days per week for \u22652 of 3 weeks during stool diary assessment. Secondary outcome was demonstration of improved colonic transit at 1 year.', 'Fifty-three patients entered long-term follow-up, and 1 patient died. Patient dissatisfaction or serious adverse events resulted in 44 patients withdrawing from the study because of treatment failure by the end of the second year. At 1 and 2 years, 10 (OR = 18.8% (95% CI, 8.3% to 29.3%)) and 3 patients (OR = 5.7% (95% CI, -0.5% to 11.9%)) met the primary outcome measure. Colonic isotope retention at 72 hours did not differ between baseline (OR = 75.6% (95% CI, 65.7%-85.6%)) and 1-year follow-up (OR = 61.7% (95% CI, 47.8%-75.6%)).",
            "output": [
                "Does sacral Nerve Stimulation fail to Offer Long-term Benefit in Patients With Slow-Transit Constipation?"
            ]
        },
        {
            "id": "task847-e25ad72c0014464eab27428425a55407",
            "input": "18\u03b2-glycyrrhetinic acid (18\u03b2-GA) has multiple beneficial and therapeutic effects. However, its protective roles on methotrexate (MTX)-induced renal injury are not well defined. In the present study, we investigated the possible protective effects of 18\u03b2-GA against MTX-induced nephrotoxicity in rats.', '18\u03b2-GA (50 and 100\\u2009mg/kg) was administered for 7 days either before or after MTX. The rats were decapitated and kidney and serum samples were collected.', 'MTX-induced renal injury in rats was evidenced by the significant (p\\u2009<\\u20090.001) increase in circulating kidney function markers and tumor necrosis factor alpha (TNF-\u03b1), as well as the histopathological alterations. MTX-induced rats exhibited significantly increased lipid peroxidation (p\\u2009<\\u20090.05) and nitric oxide (p\\u2009<\\u20090.001) levels, with concomitant marked (p\\u2009<\\u20090.001) decline in the antioxidant defenses. 18\u03b2-GA, administered either before or after MTX, produced a significant amelioration of circulating kidney function markers, TNF-\u03b1, kidney lipid peroxidation, nitric oxide, and antioxidant defenses. In addition, 18\u03b2-GA supplementation significantly up-regulated the mRNA abundance of both nuclear factor-erythroid 2-related factor 2 (Nrf2) and hemoxygenase 1 (HO-1) in the kidney of MTX-induced rats.",
            "output": [
                "Does 18\u03b2-Glycyrrhetinic acid protect against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants?"
            ]
        },
        {
            "id": "task847-ec07d18c1be4453bb62edb0432b427cc",
            "input": "Inspired by the limited facility of the Penn classification, the authors aimed to determine a rapid and optimal preoperative assessment tool to predict surgical mortality after acute Stanford type-A aortic dissection (AAAD) repair.', 'Patients who underwent an attempted surgical repair of AAAD were determined using a de-identified single institution database. The charts of 144 patients were reviewed retrospectively for preoperative demographics and surrogates for disease severity and malperfusion. Bivariate analysis was used to determine significant (p\u22640.05) predictors of in-hospital and 1-year mortality, the primary endpoints. Receiver operating characteristic curve generation was used to define optimal cut-off values for continuous predictors.', 'Single center, level 1 trauma, university teaching hospital.', 'The study included 144 cardiac surgical patients with acute type-A aortic dissection presenting for surgical correction.', 'Surgical repair of aortic dissection with preoperative laboratory samples drawn before patient transfer to the operating room or immediately after arterial catheter placement intraoperatively.', 'The study cohort comprised 144 patients. In-hospital mortality was 9%, and the 1-year mortality rate was 17%. Variables that demonstrated a correlation with in-hospital mortality included an elevated serum lactic acid level (odds ratio [OR] 1.5 [1.3-1.9], p<0.001), a depressed ejection fraction (OR 0.91 [0.86-0.96], p = .001), effusion (OR 4.8 [1.02-22.5], p = 0.04), neurologic change (OR 5.3 [1.6-17.4], p = 0.006), severe aortic regurgitation (OR 8.2 [2.0-33.9], p = 0.006), and cardiopulmonary resuscitation (OR 6.8 [1.7-26.9], p = 0.01). Only an increased serum lactic acid level demonstrated a trend with 1-year mortality using univariate Cox regression (hazard ratio 1.1 [1.0-1.1], p = 0.006). Receiver operating characteristic analysis revealed optimal cut-off lactic acid levels of 6.0 mmol/L and 6.9 mmol/L for in-hospital and 1-year mortality, respectively.",
            "output": [
                "Does hyperlactemia predict Surgical Mortality in Patients Presenting with Acute Stanford Type-A Aortic Dissection?"
            ]
        },
        {
            "id": "task847-2f872819301d497496165a6ee3621c05",
            "input": "Essentials Potentially null homozygous Factor(F)7 nonsense mutations are associated to variable bleeding symptoms. Readthrough of p.Ser112X (life-threatening) and p.Cys132X (moderate) stop codons was investigated. Readthrough-mediated insertion of wild-type or tolerated residues produce functional proteins. Functional readthrough over homozygous F7 nonsense mutations contributes to the bleeding phenotype.",
            "output": [
                "Does differential functional readthrough over homozygous nonsense mutations contribute to the bleeding phenotype in coagulation factor VII deficiency?"
            ]
        },
        {
            "id": "task847-e1a6290bdce04926bca476acfb972937",
            "input": "Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans, after basal cell carcinoma, and its incidence is dramatically rising. CSCC is rarely problematic, but given its high frequency, the absolute number of complicated cases is also high. It is necessary to identify molecular markers to recognize those CSCC with poor prognosis. There is controversy concerning the role of EGFR (epidermal growth factor receptor) as a marker of prognosis in CSCC. In addition, EGFR-targeted therapies have emerged in recent years and a better understanding of the role of EGFR in CSCC may help some patients in predicting prognosis and guide curative management.', 'We evaluated clinical and histopathological features, including events of bad clinical evolution, in a series of 94 CSCC. We also analysed EGFR expression by immunohistochemistry, FISH and QPCR.', 'We detected EGFR in 85 (90.4%) cases, with overexpression in 33 (35.1%) cases, and aberrant EGFR expression in the cytoplasm in 50 (53.1%) cases. EGFR overexpression in the primary tumours was associated with lymph node progression, TNM stage progression and proliferation (Ki-67 staining) in CSCC. EGFR overexpression and poor grade of differentiation were the strongest independent variables defining lymph node metastasis and progression in CSCC in a logistic regression model.",
            "output": [
                "Is eGFR expression associated with poor outcome in cutaneous squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-298fbbaf340c4d9b8d5e8893e868356b",
            "input": "Serum ferritin concentration >100\\xa0ng/mL was associated with a higher risk of death in hemodialysis patients in Japan, whereas such an association was less clear in hemodialysis patients in Western countries. Since Japanese dialysis patients are generally less inflamed than those in Western countries, inflammation may modify the association between serum ferritin and the adverse outcomes.', 'We performed an observational cohort study using data from 2606 Japanese hemodialysis patients who participated in the Dialysis Outcomes and Practice Patterns Study (DOPPS) III (2005-2008) or DOPPS IV (2009-2012). The predictor was serum ferritin category (<50, 50-99.9, 100-199.9, and \u2265200\\xa0ng/mL), and the primary and secondary outcomes were all-cause mortality and cardiovascular hospitalization, respectively. C-reactive protein (CRP, cut-off by 0.3\\xa0mg/dL) and serum albumin (cut-off by 3.8\\xa0g/dL) were stratification factors related to systemic inflammation.', 'After adjustment for relevant confounding factors, a U-shaped association was observed between serum ferritin and all-cause mortality in the group with low CRP levels, whereas such relationship was not significant in the high CRP counterparts. In contrast, we found a linear association between serum ferritin and cardiovascular hospitalization in the low CRP and high CRP groups commonly. Similar results were obtained when the total cohort was stratified by serum albumin.",
            "output": [
                "Do both low and high serum ferritin levels predict mortality risk in hemodialysis patients without inflammation?"
            ]
        },
        {
            "id": "task847-edea3f32f53d4d19bf0c240d4c5e415e",
            "input": "To clarify the pathways between household livestock and child growth by assessing the relationships between consumption of animal-source foods (ASF) and child growth and evaluating the household livestock correlates of child consumption of ASF.', 'We conducted a longitudinal cohort study of anthropometry and 3 d feeding recalls among children <5 years old between June 2014 and May 2015. In addition, we collected data on wealth, livestock ownership and livestock diseases in the same households. We used linear and negative binomial mixed models to evaluate the relationships between household livestock characteristics, reported consumption of ASF and child growth.', 'An 1800-household surveillance catchment area in Western Kenya within the structure of human and animal health surveillance systems.', 'Children (n 874) <5 years old.', 'Among children >6 months old, reported frequency of egg and milk consumption was associated with increased monthly height gain (for each additional report of consumption over 3 d: adjusted \u03b2 (95 % CI)=0\u00b7010 (0\u00b7002, 0\u00b7019) cm/month and 0\u00b7008 (0\u00b7004, 0\u00b7013) cm/month, respectively). Poultry ownership was associated with higher reported frequency of egg, milk and chicken consumption (adjusted incidence rate ratio (95 % CI)=1\u00b73 (1\u00b72, 1\u00b74), 1\u00b74 (1\u00b71, 1\u00b76) and 1\u00b73 (1\u00b71, 1\u00b74), respectively). Some livestock diseases were associated with lower reported frequency of ASF intake (livestock digestive diseases-adjusted incidence rate ratio (95 % CI)=0\u00b789 (0\u00b778, 1\u00b700)).",
            "output": [
                "Is child height gain associated with consumption of animal-source foods in livestock-owning households in Western Kenya?"
            ]
        },
        {
            "id": "task847-0ffdd71ab06b4338b4bc4582a7826877",
            "input": "The effect of the interaction between type 2 diabetes and dyslipidemia on inflammation and lipid peroxidation (LPO) has not been assessed.', 'To investigate whether diabetes coupled with dyslipidemia alters oxidative metabolism leading to increased LPO products and inflammatory status.', '100 patients were divided into four groups based upon diabetic and dyslipidemic status: poorly controlled diabetes with dyslipidemia (DM-PC/D), well-controlled diabetes with dyslipidemia (DM-WC/D), normoglycemic individuals with dyslipidemia (NG/D), and normoglycemic individuals without dyslipidemia (NG/ND). Plasma was evaluated for an LPO product (MDA), antioxidant levels and inflammatory cytokines.', 'Diabetics presented significantly higher levels of LPO (p<0.05) and the DM-PC/D had higher levels of proinflammatory cytokines and MDA in the plasma in comparison with normoglycemics (p<0.05). Interestingly IL1-\u03b2, IL-6, and TNF-\u03b1 in DM-WC/D were not statistically different from those in DM-PC/D. Normoglycemic individuals with dyslipidemia presented significantly increased levels of IL-6 and TNF-\u03b1 when compared to normoglycemic without dyslipidemia (p<0.05). MDA levels were also positively correlated with the presence of DM complications (r=0.42, p<0.01).",
            "output": [
                "Are diabetes and increased lipid peroxidation associated with systemic inflammation even in well-controlled patients?"
            ]
        },
        {
            "id": "task847-fef0fa0eefee42e5b99094cec259b126",
            "input": "The aim of this study was to investigate copeptin levels in serum, and assess their associations with type 2 diabetes (T2DM) and diabetic complications.', 'In this post hoc analysis, serum levels of copeptin were tested in 306 patients with T2DM. Clinical information including diabetic retinopathy (DR) and diabetic nephropathy (DN) were collected. The relation of serum copeptin with DR and DN were investigated with the use of logistic regression models according to equal quartiles of the distributions of serum copeptin.', 'We found that serum copeptin levels were significantly higher in diabetes as compared to normal controls [9.4(IQR, 7.4-12.5) pmol/L vs. 4.1(IQR, 2.5-6.2) pmol/L; P<0.0001]. In multivariate analysis, there was an increased risk of T2DM associated with copeptin levels (OR 1.312, 95% CI: 1.204-1.403; P<0.0001) after adjusting for possible confounders. After adjustment for possible confounders, serum copeptin levels were positively associated with the DR (odds ratio [OR], 1.117; 95% confidence interval [CI], 1.072-1.241; P<0.001) and DN (OR, 1.259; 95% CI, 1.198-1.323; P<0.001). Compared with the first quartile of serum copeptin levels, the ORs for DR and DN were as follows: second quartile, 1.19 (95% CI, 0.94-1.51, P=0.12) and 1.37 (95% CI, 0.78-2.37, P=0.28); third quartile, 1.61 (95% CI, 1.18-2.43, P=0.005) and 2.12 (95% CI, 1.32-3.27, P=0.003); fourth quartile, 2.83 (95% CI, 2.04-4.93; P<0.001) and 3.48 (95% CI, 1.77-7.03; P<0.001), respectively.",
            "output": [
                "Are serum levels of copeptin associated with type 2 diabetes and diabetic complications in Chinese population?"
            ]
        },
        {
            "id": "task847-4c355d967cb140e385c4c601feb4ae86",
            "input": "Resting heart rate (RHR) declines with exercise training. Possible mechanisms include: 1) increased parasympathetic tone, 2) decreased responsiveness to beta-adrenergic stimulation, 3) decreased intrinsic heart rate or 4) combination of these factors.', 'To determine whether an increase in resting parasympathetic tone or decrease in response to beta-adrenergic stimulation contributes to the decrease in RHR with training.', '51 screened healthy subjects aged 18-32 (n=20, mean age 26, 11 female) or 65-80 (n=31, mean age 69, 16 female) were tested before and after 6months of supervised exercise training. Heart rate response to parasympathetic withdrawal was assessed using atropine and beta-adrenergic responsiveness during parasympathetic withdrawal using isoproterenol.', 'Training increased VO2 max by 17% (28.7\u00b17.7 to 33.6\u00b19.20ml/kg/min, P<0.001). RHR decreased from 62.8\u00b16.6 to 57.6\u00b17.2 beats per minute (P<0.0001). The increase in heart rate in response to parasympathetic withdrawal was unchanged after training (+37.3\u00b112.8 pre vs. +36.4\u00b112.2 beats per min post, P=0.41). There was no change in the heart rate response to isoproterenol after parasympathetic blockade with training (+31.9\u00b110.9 pre vs. +31.0\u00b112.0 post beats per min, P=0.56). The findings were similar in all four subgroups.",
            "output": [
                "Is exercise training bradycardia largely explained by reduced intrinsic heart rate?"
            ]
        },
        {
            "id": "task847-0eb224cefd5942f3a32cefc841b09919",
            "input": "The Guatemalan potato tuber moth, Tecia solanivora, has been the most important pest species in Hispanico-American potato fields since its first record on potatoes in 1956 in Guatemala. This insect pest has been spreading to other parts of the world, including the Canary Islands in Europe. Tuber moth control relies heavily on the use of insecticides, including pyrethroids. Here, we assessed the likelihood of control failures and performed concentration-response bioassays in five Colombian strains of T. solanivora to evaluate their susceptibilities to the pyrethroid permethrin.', 'Evidence of control failures was observed in four strains tested, which exhibited moderate resistance levels (i.e. ranging from 5.4- to 24.4-fold). However, no spatial dependence was observed between the permethrin LC",
            "output": [
                "Is pyrethroid resistance associated with a kdr-type mutation ( L1014F ) in the potato tuber moth Tecia solanivora?"
            ]
        },
        {
            "id": "task847-69019f7696264f148dba6f0ee309b3e3",
            "input": "During a fatal Nipah virus (NiV) outbreak in Bangladesh, residents rejected biomedical explanations of NiV transmission and treatment and lost trust in the public healthcare system. Field anthropologists developed and communicated a prevention strategy to bridge the gap between the biomedical and local explanation of the outbreak.', \"We explored residents' beliefs and perceptions about the illness and care-seeking practices and explained prevention messages following an interactive strategy with the aid of photos showed the types of contact that can lead to NiV transmission from bats to humans by drinking raw date palm sap and from person-to-person.\", 'The residents initially believed that the outbreak was caused by supernatural forces and continued drinking raw date palm sap despite messages from local health authorities to stop. Participants in community meetings stated that the initial messages did not explain that bats were the source of this virus. After our intervention, participants responded that they now understood how NiV could be transmitted and would abstain from raw sap consumption and maintain safer behaviours while caring for patients.",
            "output": [
                "'s it only what you say , it 's also how you say it : communicating nipah virus prevention messages during an outbreak in Bangladesh?"
            ]
        },
        {
            "id": "task847-5a662208ab774196aa152191d48ceee2",
            "input": "A safety event drew attention to unsafe and inappropriate payer formulary alerts. These alerts display formulary, coverage, and eligibility data from the pharmacy benefits manager in response to an electronic prescription. They are intended to redirect prescribers to medications that are covered by insurance; however, these alerts were found to be inaccurate and contribute to potentially harmful alerts. Our objective was to reduce inappropriate payer formulary alerts by 30% within 1 year and to change the ePrescribing certification requirements to prevent future instances of harm.', 'Using process mapping we identified the changes that were required both locally and nationally through our electronic health record (EHR) vendor and ePrescribing transaction broker. We partnered with vendors to show the safety risk and to suggest modifications to the payer formulary alert content and ePrescribing certification criteria. On the basis of the new criteria, we modified and deactivated inappropriate alerts. Rates were followed weekly for 13 months and a control chart was used to track progress.', 'From January 2014 to January 2015, we reviewed 59\\u2009325 payer formulary alerts from ambulatory care and 11\\u2009630 from the emergency department and inpatient wards. Both local and national modifications resulted in significant and sustained decreases in inappropriate alerts.",
            "output": [
                "Does payer Formulary alert as a Cause of Patient Harm and the Journey to Change Them?"
            ]
        },
        {
            "id": "task847-3ff41bf1fc314fe6bb4c9db24137d7d1",
            "input": "Bleeding in ACS patients is an independent marker of adverse outcomes. Its prognostic impact is even worse in elderly population. Current bleeding risk scores include chronological age but do not consider biologic vulnerability. No studies have assessed the effect of frailty on major bleeding. The aim of this study is to determine whether frailty status increases bleeding risk in patients with ACS.', 'This prospective and observational study included patients aged \u226575years admitted due to type 1 myocardial infarction. Exclusion criteria were severe cognitive impairment, impossibility to measure handgrip strength, cardiogenic shock and limited life expectancy due to oncologic diseases. The primary endpoint was 30-day major bleeding defined as a decrease of \u22653g/dl of haemoglobin or need of transfusion.', 'A total of 190 patients were included. Frail patients (72, 37.9%) were older, with higher comorbidity features and with a higher CRUSADE score at admission. On univariate analysis, frailty predicted major bleeding during 30-day follow-up despite less frequent use of a P2Y12 inhibitor (66.2% vs 83.6%, p=0.007) and decreased catheterisation rate (69.4% vs 94.1%, p<0.001). Major bleeding was associated with increased all-cause mortality at day 30 (18.2% vs 2.5%, p<0.001). On multivariate analysis, frailty was an independent predictor for major bleeding.",
            "output": [
                "Does frailty predict major bleeding within 30days in elderly patients with Acute Coronary Syndrome?"
            ]
        },
        {
            "id": "task847-9fb76bdd91474b95840e4fb343ab25c3",
            "input": "In anorexia nervosa (AN) hypercortisolism has been described using urine, plasma and saliva samples as short-term markers for the hypothalamic-pituitary-adrenal (HPA)-axis. Here, for the first time, we analyse hair cortisol concentration (HCC) as a marker for long-term integrated cortisol secretion in female patients with AN compared to female healthy controls (HC) and female psychiatric controls (PC).', 'HCC was assessed in 22 female adolescent psychiatric inpatients with AN compared to 20 female HC and to 117 female PC of the same age range. For further analyses we examined the associations of age and body mass index (BMI) with HCC.', 'Log HCC was lower in AN-patients compared to HC (p\\u2009=\\u20090.030). BMI-standard deviation scores (SDS) but not age correlated with log HCC (BMI-SDS: r\\u2009=\\u20090.19, bias corrected accelerated 95% confidence interval: [.04, .34], p\\u2009=\\u20090.015; age: r\\u2009=\\u20090.10, bias corrected accelerated 95% confidence interval: [-.07, .25], p\\u2009=\\u20090.213) when combining AN, HC and PC samples.",
            "output": [
                "Are hair Cortisol Concentrations in Adolescent Girls with Anorexia Nervosa Lower Compared to Healthy and Psychiatric Controls?"
            ]
        },
        {
            "id": "task847-9e61a1a50e6f4e92bad9ca1b6e619e20",
            "input": "Sleep plays a central role in maintaining health and cognition. In most epidemiologic studies, sleep is evaluated by self-report questionnaires but several reports suggest that these evaluations might be less accurate than objective measures such as polysomnography or actigraphy. Determinants of the discrepancy between objective and subjective measures remain to be investigated. The aim of this pilot-study was to examine the role of mood states in determining the discrepancy observed between objective and subjective measures of sleep duration in older adults.', 'Objective sleep quantity and quality were recorded by actigraphy in a sample of 45 elderly subjects over at least three consecutive nights. Subjective sleep duration and supplementary data, such as mood status and memory, were evaluated using ecological momentary assessment (EMA).', \"A significant discrepancy was observed between EMA and actigraphic measures of sleep duration (p < 0.001). The magnitude of this difference was explained by the patient's mood status (p = 0.020). No association was found between the magnitude of this discrepancy and age, sex, sleep quality or memory performance.",
            "output": [
                "Does mood influence the Concordance of Subjective and Objective Measures of Sleep Duration in Older Adults?"
            ]
        },
        {
            "id": "task847-184c747c58f54a5f936f3f5a6c6250e5",
            "input": "The prognostic relevance of bacterial DNA (bactDNA) detection in ascitic fluid of patients with cirrhosis is still under debate. Using quantitative real-time PCR with broad-range primers targeting the V3 and V4 variable region of the 16S rRNA gene, we measured bactDNA concentrations in patients with and without leukocytic ascites and evaluated the impact on short-term survival.', 'Ascites samples from 173 patients with decompensated cirrhosis were consecutively collected between February 2011 and December 2012. BactDNA-positive ascites samples were sequenced and chromatograms were identified using RipSeq. Clinical data collection and survival analyses were carried out retrospectively and correlated with ascites bactDNA levels.', \"BactDNA was detected qualitatively with a similar frequency in both nonleukocytic and leukocytic ascites [40% (57/144) and 43.5% (10/23), respectively; P=0.724]. However, the median bactDNA level was significantly higher in leukocytic ascites than in nonleukocytic ascites (1.2\u00d710 vs. 5.7\u00d710\\u2009copies/ml; P=0.008). Patients' survival was associated significantly with bactDNA level. The 30-day and 180-day survival was reduced if bactDNA was above the quantification limit of 520\\u2009copies/ml (84 and 63% vs. 72 and 43%, respectively; P<0.05) and worst if bactDNA was above 5000\\u2009copies/ml. The bacterial spectrum was dominated by Gram-positive strains as shown by direct sequencing.",
            "output": [
                "Does detection of molecular bacterascites in decompensated cirrhosis define a risk with decreased survival?"
            ]
        },
        {
            "id": "task847-cf6fd0604b6846b09f0e104cd61e1ba2",
            "input": "To describe the variability in rheumatology visits and referrals to other medical specialties of patients with spondyloarthritis (SpA) and to explore factors that may influence such variability.', 'Nation-wide cross-sectional study performed in 2009-2010. Randomly selected records of patients with a diagnosis of SpA and at least one visit to a rheumatology unit within the previous 2\\xa0years were audited. The rates of rheumatology visits and of referrals to other medical specialties were estimated-total and between centres-in the study period. Multilevel regression was used to analyse factors associated with variability and to adjust for clinical and patient characteristics.', \"1168 patients' records (45 centres) were reviewed, mainly ankylosing spondylitis (55.2\\xa0%) and psoriatic arthritis (22.2\\xa0%). The patients had incurred in 5908 visits to rheumatology clinics (rate 254 per 100 patient-years), 4307 visits to other medical specialties (19.6\\xa0% were referrals from rheumatology), and 775 visits to specialised nurse clinics. An adjusted variability in frequenting rheumatology clinics of 15.7\\xa0% between centres was observed. This was partially explained by the number of faculties and trainees. The adjusted intercentre variability for referrals to other specialties was 12.3\\xa0%, and it was associated with urban settings, number of procedures, and existence of SpA dedicated clinics; the probability of a patient with SpA of being referred to other specialist may increase up to 25\\xa0% depending on the treating centre.",
            "output": [
                "Do centre characteristics determine ambulatory care and referrals in patients with spondyloarthritis?"
            ]
        },
        {
            "id": "task847-74f26829ecf5495590b15bb150ceb7a6",
            "input": "Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation.', 'Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status.', 'Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample.",
            "output": [
                "Is a Novel Mutation in the DNA Binding Domain of NFKB Associated with Speckled Leukoplakia?"
            ]
        },
        {
            "id": "task847-eed86bee126047a0992ab8f3f6a842b6",
            "input": "During reactive hyperemia, the brachial artery in some individuals constricts prior to dilation. Our aim was to describe the frequency of high-flow-mediated constriction (H-FMC) in adults, and its relationship to body composition and biomarkers of cardiovascular and metabolic risk.', 'Two hundred forty-six adults (124 male, 122 female; 36\\u2009\u00b1\\u20097 years old) were assessed for H-FMC via sonographic imaging of the brachial artery. Blood pressure, glucose, insulin, lipids, and body composition assessed via dual energy X-ray absorptiometry were collected. H-FMC was characterized as a 10-second average of maximal postocclusion constriction. Independent t test was used to compare H-FMC versus non-H-FMC individuals.', 'H-FMC was observed in approximately 69% of adult participants (54 obese, 57 overweight, and 59 normal weight). Total body mass (82.3\\u2009\u00b1\\u200917.5 versus 76.3\\u2009\u00b1\\u200916.3 kg, p\\u2009=\\u20090.012), fat mass (27.7\\u2009\u00b1\\u200911.5 versus 23.8\\u2009\u00b1\\u200910.5 kg, p\\u2009=\\u20090.012), body mass index (27.7\\u2009\u00b1\\u20094.9 versus 26.1\\u2009\u00b1\\u20095.0 kg/m",
            "output": [
                "Is high-flow-mediated constriction in adults influenced by biomarkers of cardiovascular and metabolic risk?"
            ]
        },
        {
            "id": "task847-2afdcdbd43c044de9b65e50b6050dc9e",
            "input": "The study aimed to investigate key intrafollicular prognostic factors among various cytokines and angiogenic molecules for prediction of mature oocytes and good-quality embryos in women with endometriosis undergoing in vitro fertilization (IVF).', 'Paired follicular fluid and serum samples were collected from 200 women with advanced stage endometriosis and 140 normal ovulating women during oocyte retrieval. The concentrations of cytokines (pro-inflammatory: IL-1\u03b2, TNF-\u03b1, IL-2, IL-8, IL-12, IFN-\u03b3; anti-inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular fluid and serum using ELISA. Expression of these molecules was subjected to multivariate analysis for the identification of major predictive markers of oocyte and embryo quality. Receiver operating characteristic (ROC) curve was applied to determine the best cutoff point for the discrimination between mature and immature oocytes in these women.', 'Significant increases in levels of cytokines and angiogenic molecules were observed in women with endometriosis compared to controls (P\\u2009<\\u20090.001). From the validated partial least squares-discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were identified as the most important factors contributing to endometriosis and were negatively associated with oocyte maturity and embryo quality.",
            "output": [
                "Are intrafollicular interleukin-8 , interleukin-12 , and adrenomedullin the promising prognostic markers of oocyte and embryo quality in women with endometriosis?"
            ]
        },
        {
            "id": "task847-639a27b1f4194f1daa1560f45f4490af",
            "input": "Knowledge of sepsis-related end-organ inflammation in\\xa0vivo is limited. We investigated the cytokine response in skin and in serum in sepsis and its relation to multiorgan failure (MOF) and survival.', 'Cytokines were analysed in serum and in suction blister fluid of intact skin of 44 patients with severe sepsis and 15 healthy controls. Blister fluid and serum samples were collected within 48\\xa0h of the first sepsis-induced organ failure. This is a substudy of a larger follow-up study on wound healing in sepsis.', 'Cytokine levels were higher in patients with sepsis vs. controls (interleukin [IL]-10, blisters: 65.9 vs. 4.3\\xa0pg/ml, P\\xa0<\\xa00.001, serum: 25.7 vs. 4.5\\xa0pg/ml, P\\xa0=\\xa00.004; IL-6, blisters: 41.9 vs. 0.03\\xa0pg/ml, P\\xa0<\\xa00.001, serum: 45.5 vs. 2.1\\xa0pg/ml, P\\xa0<\\xa00.001). Patients with MOF had higher levels of IL-10 (116.4 vs. 21.3\\xa0pg/ml, P\\xa0=\\xa00.015), IL-4 (0.7 vs. 0.07\\xa0pg/ml, P\\xa0=\\xa00.013) and basic fibroblast growth factor (bFGF) (25.9 vs. 9.5\\xa0pg/ml, P\\xa0=\\xa00.027) in blister fluid than patients without MOF. In blister fluid, survivors had lower levels of IL-10 (43.3 vs. 181.9\\xa0pg/ml, P\\xa0=\\xa00.024) and bFGF (15.8 vs. 31.9\\xa0pg/ml, P\\xa0=\\xa00.006) than non-survivors. In serum, survivors had higher levels of vascular endothelial growth factor (VEGF) (152.2 vs. 14.7\\xa0pg/ml, P\\xa0=\\xa00.012) and lower levels of IL-6 (38.5 vs. 91.1\\xa0pg/ml, P\\xa0=\\xa00.011) than non-survivors. The blister fluid levels of bFGF, TNF and VEGF did not correlate with the serum levels.",
            "output": [
                "Do blister fluid and serum cytokine levels in severe sepsis in humans reflect skin dysfunction?"
            ]
        },
        {
            "id": "task847-61aec0de89b640beb7982754c5223bc4",
            "input": "Dyspnoea is a threatening sensation of respiratory discomfort that presents many similarities with pain. Experimental dyspnoea in healthy subjects induces analgesia. This 'dyspnoea-pain counter-irritation' could, in reverse, imply that relieving dyspnoea in patients with chronic respiratory diseases would lower their pain thresholds.\", 'We first determined pressure pain thresholds in 25 healthy volunteers (22-31\\u2005years; 13 men; handheld algometer), during unloaded breathing (BASELINE) and during inspiratory threshold loading (ITL). Two levels of loading were used, adjusted to induce dyspnoea self-rated at 60% or 80% of a 10\\u2005cm visual analogue scale (ITL6 and ITL8). 18 patients with chronic respiratory failure due to amyotrophic lateral sclerosis (ALS) were then studied during unassisted breathing and after 30 and 60\\u2005min of non-invasive ventilation-NIV30 and NIV60-(same dyspnoea evaluation).', 'In healthy volunteers, pressure pain thresholds increased significantly in the deltoid during ITL6 (p<0.05) and ITL8 (p<0.05) and in the trapezius during ITL8 (p<0.05), validating the use of pressure pain thresholds to study dyspnoea-pain counter-irritation. In patients with ALS, the pressure pain thresholds measured in the deltoid during unassisted breathing decreased by a median of 24.5%-33.0% of baseline during NIV30 and NIV60 (p<0.05).",
            "output": [
                "Does relieving dyspnoea by non-invasive ventilation decrease pain thresholds in amyotrophic lateral sclerosis?"
            ]
        },
        {
            "id": "task847-7de4c3af900d4f1dbb79c2111905aefc",
            "input": "The human microbiota is a modulator of the immune system. Variations in the placental microbiota could be related with pregnancy disorders. We profiled the placental microbiota and microbiome in women with gestational diabetes (GDM) and studied its relation to maternal metabolism and placental expression of anti-inflammatory cytokines.', \"Placental microbiota and microbiome and expression of anti-inflammatory cytokines (IL10, TIMP3, ITGAX, and MRC1MR) were analyzed in placentas from women with GDM and from control women. Fasting insulin, glucose, O'Sullivan glucose, lipids, and blood cell counts were assessed at second and third trimester of pregnancy.\", \"Bacteria belonging to the Pseudomonadales order and Acinetobacter genus showed lower relative abundance in women with GDM compared to control (P < 0.05). In GDM, lower abundance of placental Acinetobacter associated with a more adverse metabolic (higher O'Sullivan glucose) and inflammatory phenotype (lower blood eosinophil count and lower placental expression of IL10 and TIMP3) (P < 0.05 to P = 0.001). Calcium signaling pathway was increased in GDM placental microbiome.",
            "output": [
                "Is gestational diabetes associated with changes in placental microbiota and microbiome?"
            ]
        },
        {
            "id": "task847-c1b06f3f62a6453b9150655d04e58860",
            "input": "The preterm newborn is at high risk of developing cardiovascular compromise during the first day of life and this is associated with increased risk of brain injury. Standard treatments are volume expansion and administration of inotropes, typically dopamine and/or dobutamine, but there is limited evidence that inotropes improve clinical outcomes. This study investigated the efficacy of dopamine and dobutamine for the treatment of cardiovascular compromise in the preterm newborn using a piglet model.', 'Preterm and term piglets were assigned to either dopamine, dobutamine or control infusions. Heart rate, left ventricular contractility, cardiac output, blood pressure, and cerebral and regional blood flows were measured during baseline, low (10 \u00b5g/kg/h), and high (20 \u00b5g/kg/h) dose infusions.', 'At baseline, preterm piglets had lower cardiac contractility, cardiac output, blood pressure, and cerebral blood flow compared to term piglets. The response of preterm piglets to either dopamine or dobutamine administration was less than in term piglets. In both preterm and term piglets, cardiac output and cerebral blood flow were unaltered by either inotrope.",
            "output": [
                "Do inotropes increase cardiac output or cerebral blood flow in preterm piglets?"
            ]
        },
        {
            "id": "task847-d15733af57e946d29c0a35ff64c60721",
            "input": "PTH stimulates bone formation in Fgfr3 knockout mice through promotion of proliferation and differentiation in osteoblasts.', 'Previous studies showed that endogenous fibroblast growth factor 2 (FGF-2) is required for parathyroid hormone (PTH)-stimulated bone anabolic effects, however, the exact mechanisms by which PTH stimulate bone formation and the function of FGF receptors in mediating these actions are not fully defined. FGF receptor 3 (FGFR3) has been characterized as an important regulator of bone metabolism and is confirmed to cross-talk with PTH/PTHrP signal in cartilage and bone development.', 'Fgfr3 knockout and wild-type mice at 2-month-old and 4-month-old were intraperitoneally injected with PTH intermittently for 4 weeks and then the skeletal responses to PTH were assessed by dual energy X-ray absorptiometry (DEXA), micro-computed tomography (\u03bcCT) and bone histomorphometry.', 'Intermittent PTH treatment improved bone mineral density (BMD) and femoral mechanical properties in both Fgfr3 (-/-) and wild-type mice. Histomorphometric analysis showed that bone formation and bone resorption were increased in both genotypes following PTH treatment. PTH treatment increased trabecular bone volume (BV/TV) in WT and Fgfr3-deficient mice. The anabolic response in Fgfr3-deficient and wild-type bone is characterized by an increase of both bone formation and resorption-related genes following PTH treatment. In addition, we found that Fgfr3 null osteoblasts (compared to wild-type controls) maintained normal abilities to response to PTH-stimulated increase of proliferation, differentiation, expression of osteoblastic marker genes (Cbfa1, Osteopontin and Osteocalcin), and phosphorylation of Erk1/2.",
            "output": [
                "Does fibroblast Growth Factor Receptor 3 Deficiency Impair the Osteoanabolic Action of Parathyroid Hormone on Mice?"
            ]
        },
        {
            "id": "task847-b03afb822bc54c21aa0889315b5bbb5d",
            "input": "Our previous studies suggested that brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) axis inhibited cardiomyocyte apoptosis in myocardial infarction (MI). However, the relationship between BDNF and microRNA (miRNA) in cardiomyocytes are unclear. The present study was performed to investigate the role of miR-195 and the interplay between BDNF and miR-195 in ischemic cardiomyocyte apoptosis.', 'Male Wistar rats were subjected to coronary artery ligation, and primary neonatal rat ventricular myocytes were treated with hypoxia or hydrogen peroxide (H2O2). BDNF level in rat ventricles was measured by enzyme linked immunosorbent assay (ELISA). miR-195 mimic, inhibitor or negative control was transfected into the cardiomyocytes. Cell viability and apoptosis were detected by MTT assay and TdT-mediated dUTP nick end labeling (TUNEL) staining, respectively. Cardiac function and apoptosis were detected in MI rats intravenously injected with antagomiR-195. Luciferase assay, Western blot and Real-time RT-PCR were employed to clarify the interplay between miR-195 and BDNF.', 'miR-195 level was dynamically regulated in response to MI and significantly increased in ischemic regions 24 h post-MI as well as in hypoxic or H2O2-treated cardiomyocytes. Meanwhile, BDNF protein level was rapidly increased in MI rats and H2O2-treated cardiomyocytes. Apoptosis in both hypoxic and H2O2-treated cardiomyocytes were markedly reduced and cell viability was increased by miR-195 inhibitor. Moreover, inhibition of miR-195 significantly improved cardiac function of MI rats. Bcl-2 but not BDNF was validated as the direct target of miR-195. Furthermore, BDNF abolished the pro-apoptotic role of miR-195, which was reversed by its scavenger TrkB-Fc.",
            "output": [
                "Does bDNF-mediates Down-regulation of MicroRNA-195 inhibit Ischemic Cardiac Apoptosis in Rats?"
            ]
        },
        {
            "id": "task847-c6eb809a880a4197bd1b2fcba2d631fd",
            "input": "Oxidative stress is proposed as a central mediator in NAFLD pathogenesis, but the specific trigger for reactive oxygen species generation has not been clearly delineated. In addition, emerging evidence shows that obesity related obstructive sleep apnea (OSA) and nocturnal hypoxia are associated with NAFLD progression in adults. The aim of this study was to determine if OSA/nocturnal hypoxia-induced oxidative stress promotes the progression of pediatric NAFLD.', 'Subjects with biopsy proven NAFLD and lean controls were studied. Subjects underwent polysomnograms, liver histology scoring, laboratory testing, urine F(2)-isoprostanes (measure of lipid peroxidation) and 4-hydroxynonenal liver immunohistochemistry (in situ hepatic lipid peroxidation).', 'We studied 36 adolescents with NAFLD and 14 lean controls. The OSA/hypoxia group (69% of NAFLD subjects) had more severe fibrosis (64% stage 0-2; 36% stage 3) than those without OSA/hypoxia (100% stage 0-2), p=0.03. Higher F(2)-isoprostanes correlated with apnea/hypoxia index (r=0.39, p=0.03), % time SaO2 <90% (r=0.56, p=0.0008) and inversely with SaO2 nadir (r=-0.46, p=0.008). OSA/hypoxia was most severe in subjects with the greatest 4HNE staining (p=0.03). Increasing F(2)-isoprostanes(r=0.32, p=0.04) and 4HNE hepatic staining (r=0.47, p=0.007) were associated with worsening steatosis. Greater oxidative stress occurred in subjects with definite NASH as measured by F(2)-isoprostanes (p=0.06) and hepatic 4HNE (p=0.03) compared to those with borderline/not NASH.",
            "output": [
                "Does nocturnal hypoxia-induced oxidative stress promote progression of pediatric non-alcoholic fatty liver disease?"
            ]
        },
        {
            "id": "task847-fd3e12d54cb14cf1a0f7d47274d8d1e1",
            "input": "Decortication for thoracic empyema is associated with significant blood loss and prolonged postoperative air leak. We sought to assess the potential application of an irrigated-tip radiofrequency (RF) sealing device, in an attempt to reduce this morbidity.', \"Data for all patients undergoing open decortication (OD) for stage II thoracic empyema, using either conventional approach or facilitated by use of the Aquamantys(\u00ae) device, at a single thoracic surgical unit between April 2010 and July 2014, were retrospectively analysed. Unpaired t-test and Fisher's exact test were used for statistical analysis.\", 'Thirty-three patients, aged 54\u00b115 years (mean \u00b1 SD), and with a Charlson comorbidity index of 2.5\u00b11.9 were included. Preoperative and intraoperative characteristics, including surgical time, were similar in the conventional and Aquamantys(\u00ae) groups. Patients in the Aquamantys group were less likely to require red cell transfusion (9/22 vs. 10/11 patients, P=0.024) and received lower volume transfusions [0.0 (2.0) vs. 3.0 (1.6) units (median, IQR), P<0.0001]; chest drain duration was shorter [3.0 (1.0) vs. 6.5 (6.8) days, P=0.006], as was length of postoperative hospital stay [6.0 (8.7) vs. 10.0 (4.6) days, P=0.031]. There was no demonstrable difference in mortality.",
            "output": [
                "Does the Aquamantys ( \u00ae ) system improve haemostasis and pneumostasis in open decortication for thoracic empyema?"
            ]
        },
        {
            "id": "task847-b347a61c39f34580b01b203312c357bc",
            "input": "Oral epithelial cells have currently been found to play an important role in inflammatory modulation in periodontitis. Mangiferin is a natural glucosylxanthone with anti-inflammatory activity. The aim of this study was to investigate the regulatory effect of mangiferin on lipopolysaccharide (LPS)-induced production of proinflammatory cytokine interleukin-6 (IL-6) in oral epithelial cells and the underlying mechanisms.', 'The levels of LPS-induced IL-6 production in OKF6/TERT-2 oral keratinocytes were detected using enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor (TLR) 2 and TLR4 was determined using western blot analysis. And the phosphorylation of TLR downstream nuclear factor-\u03baB (NF-\u03baB), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) was examined using cell-based protein phosphorylation ELISA kits.', 'We found that mangiferin reduced LPS-upregulated IL-6 production in OKF6/TERT-2 cells. Additionally, mangiferin inhibited LPS-induced TLR2 and TLR4 overexpression, and suppressed the phosphorylation of NF-\u03baB, p38 MAPK and JNK. Moreover, mangiferin repressed IL-6 production and TLR signaling activation in a dose-dependent manner after 24h treatment.",
            "output": [
                "Does mangiferin inhibit lipopolysaccharide-induced production of interleukin-6 in human oral epithelial cells by suppressing toll-like receptor signaling?"
            ]
        },
        {
            "id": "task847-936572029eb0415fab002ef1beb61f9c",
            "input": "There is increasing evidence linking arterial (mainly aortic) stiffness and type 2 diabetes, a risk factor for arterial stiffness, to cognitive impairment and dementia. However, data on carotid stiffness, which may be especially relevant for cognitive performance, are scarce, and few studies have addressed the interplay between arterial stiffness, type 2 diabetes, and cognitive performance.', \"We studied individuals with (n\\xa0=\\xa0197) and without (n\\xa0=\\xa0528) type 2 diabetes, who completed a neuropsychological test battery and underwent applanation tonometry and vascular ultrasound to evaluate aortic (i.e. carotid-to-femoral pulse wave velocity) and carotid stiffness (i.e. distensibility, compliance and Young's elastic modulus). Linear regression analyses were performed and adjusted for demographics, vascular risk factors, and depression.\", \"Overall, our results showed that carotid, but not aortic, stiffness was associated with worse cognitive performance, primarily in the domains of processing speed (standardized regression coefficient for distensibility\\xa0-0.083, p\\xa0=\\xa00.040; compliance\\xa0-0.077, p\\xa0=\\xa00.032) and executive function and attention (distensibility\\xa0-0.133, p\\xa0=\\xa00.001; compliance\\xa0-0.090, p\\xa0=\\xa00.015; Young's elastic modulus\\xa0-0.081, p\\xa0=\\xa00.027). These associations did not differ by diabetes status. The differences in cognitive performance between individuals with and without type 2 diabetes (mean difference in domain scores relative to those without diabetes for free recall memory\\xa0-0.23, processing speed\\xa0-0.19, executive function and attention\\xa0-0.23; all p\\xa0\u2264\\xa00.009 and adjusted for demographics, traditional vascular risk factors, and depression) were not substantially altered after additional adjustment for carotid stiffness.",
            "output": [
                "Is carotid stiffness associated with impairment of cognitive performance in individuals with and without type 2 diabetes . The Maastricht Study?"
            ]
        },
        {
            "id": "task847-976a2b9ef29e464baec7f1606948d2bd",
            "input": "Various methods have been used to objectively record skin changes. However, estimating the intrinsic and extrinsic aging of skin remains a challenge. Our objective was to study intrinsic skin aging with respect to patient age and extrinsic photo-aging of human dorsal (photo-exposed) and volar (photo-protected) forearm in vivo through skin auto-fluorescence (AF). We also examined the correlations between serum antioxidant enzyme, malondialdehyde(MDA), and skin AF.', '37 healthy volunteers were enrolled. We measured skin AF and its heterogeneity on the dorsal and volar forearms. We also examined serum concentration of catalase, superoxide dismutase, vitamin E, and MDA levels in every participant.', 'In photo-protected areas, skin AF intensity in the 40 years or older group was significantly higher compared to the group less than 40 years-old. On the other hand, heterogeneity value was significantly higher in the less than 40 years-old group in photo-protected area. With respect to serum antioxidant enzyme and MDA level, only MDA level showed a negative correlation with skin AF intensity in photo-exposed area.",
            "output": [
                "Is pilot study on the correlation between skin auto-fluorescence and serum antioxidant enzyme : skin auto-fluorescence negatively associated with levels of malondialdehyde?"
            ]
        },
        {
            "id": "task847-2e62823483454516ae0e22a3ca8bb0ac",
            "input": "Some living kidney donors report lost income during recovery from surgery. Little is known about whether concern for living donor's lost income affects the decision to undergo donation evaluation and the willingness of transplant candidates to discuss living kidney donation (LKD) with others.\", 'To examine whether transplant patients were told by potential donors about lost income concerns and whether patients chose not to discuss LKD with others due to lost income concerns.', \"Kidney transplant patients (185 wait-listed candidates, 171 deceased donor recipients, and 100 live donor recipients) at 2 centers completed a questionnaire to assess whether concern about donor's lost income was a consideration in discussion about LKD with others.\", 'One-third (32%) were told by a family member/friend that they were willing to donate but were concerned about potential lost income. The majority of those who expressed financial concern (64%) did not initiate donation evaluation. Many patients (42%) chose not to discuss living donation with a family member/friend due to concern about the impact of lost income on the donor. In the multivariable model, lower annual household income was the only statistically significant predictor of both having a potential donor expressing lost income concern and choosing not to talk to someone because of lost income concern.",
            "output": [
                "Does concern for Lost Income Following Donation deter Some Patients From Talking to Potential Living Donors?"
            ]
        },
        {
            "id": "task847-c6247a335d7345cba6e7736ac70dbfe2",
            "input": "The aim of this study was to evaluate the effect of povidone-iodine rectal disinfection and targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound-guided prostate biopsy based on rectal swab culture results.', 'From January 2011 to December 2015, we studied differences in infectious complications in men who received povidone-iodine rectal disinfection with targeted antimicrobial prophylaxis and those who received empirical prophylaxis before transrectal ultrasound-guided prostate biopsy. Clinical variables including demographics, prior antibiotic, rectal swab culture results, povidone-iodine rectal cleansing, antibiotic prophylaxis, and infectious complications were evaluated. Patients were divided into three groups as follows: Group A received no povidone-iodine rectal cleansing but received empirical antimicrobial prophylaxis; group B received povidone-iodine rectal cleansing and empirical antimicrobial prophylaxis; and group C received povidone-iodine rectal cleansing and targeted antimicrobial prophylaxis.', 'Patients were divided into group A (n\\xa0=\\xa0192; 13.2\\xa0%), group B (n\\xa0=\\xa0579; 39.9\\xa0%), or group C (n\\xa0=\\xa0679; 46.8\\xa0%). In groups A and B, all patients received fluoroquinolone antimicrobial prophylaxis. Group C patients received targeted antimicrobial prophylaxis according to antibiotic resistance of rectal flora, and 71.1\\xa0% of these received fluoroquinolone antimicrobial prophylaxis. Infectious complication rates were 3.6, 2.9, and 1.3\\xa0% in group A, group B, and group C, respectively. Incidences of acute prostatitis and bacteremia were significantly lower in group C (p\\xa0=\\xa00.041 and p\\xa0=\\xa00.049, respectively) than in the other groups.",
            "output": [
                "Are povidone-iodine rectal cleansing and targeted antimicrobial prophylaxis using rectal swab cultures in men undergoing transrectal ultrasound-guided prostate biopsy associated with reduced incidence of postoperative infectious complications?"
            ]
        },
        {
            "id": "task847-4b4fb3f322a34c54a350f0f0c99bfab2",
            "input": "The pathogenesis and the clinical impact of diastolic dysfunction (DD) in cirrhosis remain unclear. Our aim was to investigate the factors significantly associated with the presence of DD in patients with decompensated cirrhosis on the waiting list for liver transplantation.', 'consecutive patients with decompensated cirrhosis, who admitted for transplant assessment, were prospectively evaluated. We assessed the independent factors associated with the presence of DD, while their discriminative ability was evaluated by AUC curve. The diagnosis of DD was based on Doppler echocardiography and classified into three categories according to the current guidelines.', 'we evaluated 115 consecutive patients. Sixty six patients (57.3%-group 1) had DD and 49 (42.7%-group 2) had not DD. The 2 groups had similar Child-Pugh/MELD scores and survival. In multivariable logistic regression analysis, pulse rate (OR: 1.082, 95% CI: 1.03-1.15, p = 0.004), and UNa24h (OR: 0.98, 95% CI: 0.97- 0.99, p = 0.004) were the only variables independently associated with the presence of DD. In the subgroup of consecutive patients (n = 31) with evaluation of cytokines, those (n = 22) with DD, compared to those (n = 9) without DD, had significantly higher levels of inteleukin-6 [145 (45-2000) vs. 56 (10-149)pg/mL, p = 0.043].",
            "output": [
                "Is diastolic dysfunction associated with low urinary sodium excretion in patients with decompensated cirrhosis?"
            ]
        },
        {
            "id": "task847-7b05b930f24e4e43a0c038d0f1ec5a3a",
            "input": "Studies have revealed a phenomenon called skin-deep resilience, which develops in upwardly mobile African American youth. They perform well in school, maintain good mental health, and avoid legal problems. Despite outward indications of success, they also show evidence of worse health in biomarker studies. Here we extend this research, asking whether it manifests in differential susceptibility to upper respiratory infection, and if it emerges in European Americans as well.', 'The sample included 514 adults in good health, as judged by physician examination and laboratory testing. Participants completed questionnaires about lifecourse socioeconomic conditions, conscientiousness, psychosocial adjustment, and lifestyle factors. They were subsequently inoculated with a rhinovirus that causes upper respiratory infection, and monitored in quarantine for 5 days the development of illness.', \"Consistent with past work, African Americans from disadvantaged backgrounds displayed indications of skin-deep resilience. To the extent these participants were high in conscientiousness, they fared better across multiple domains of psychosocial functioning, as reflected in educational attainment, symptoms of depression, and close relationship quality (p values = .01-.04). But analyses of these participants' susceptibility to infection revealed the opposite pattern; higher conscientiousness was associated with a greater likelihood of becoming ill following inoculation (p value = .03). In European Americans, there was no evidence of skin-deep resilience; conscientiousness was associated with better psychosocial outcomes, but not infection risk.",
            "output": [
                "Does viral challenge reveal further evidence of skin-deep resilience in African Americans from disadvantaged backgrounds?"
            ]
        },
        {
            "id": "task847-bff57936fb5345bf98418ea8f2fb98f8",
            "input": "The ADAMTS13-von Willebrand factor (vWF) axis has been suggested to play a critical role in the pathophysiology of ischemia-reperfusion injury (IRI) in the heart or brain. Therefore, we aimed to investigate whether this axis was involved in the pathophysiology of IRI-induced acute kidney injury.', 'We performed renal IRI in ADAMTS13 knockout (KO) or wild type (WT) mice. Functional and histological kidney damage, and inflammation were compared and the effect of anti-vWF antibodies in ADAMTS13 KO mice was assessed.', 'Following IRI, the blood and kidney ADAMTS13 levels were significantly decreased. vWF expression was significantly upregulated in both the medulla and cortex of injured kidneys as shown by immunohistochemistry and western blot analyses. There was also an increased level of vWF dimers after IRI. In ADAMTS13 KO mice, kidney vWF levels were further increased and this was associated with greater endothelial and epithelial injury compared to WT mice, suggesting an important role of vWF in renal IRI. In addition, the number of Gr-1",
            "output": [
                "Is the ADAMTS13-von Willebrand factor axis involved in the pathophysiology of kidney ischemia-reperfusion injury?"
            ]
        },
        {
            "id": "task847-9f3f2821f8884b94a0839458b3fa1f42",
            "input": "Citrus canker is an economically important disease caused by the bacterial pathogen Xanthomonas citri subsp. citri (Xcc). This organism targets a wide range of citrus plants, including sweet orange, grapefruit, lemon and lime. As Xcc is spread by environmental factors such as wind and rain, it is difficult to control its movement once the disease has established. In order to facilitate monitoring of citrus canker we sought to design a novel diagnostic protocol based on fluorescence in\\xa0situ hybridization (FISH) for identification of bacterial cells directly from canker pustules without cultivation or DNA extraction. This method was validated for specificity against a range of Xanthomonas species and strains. We show that our assay is extremely rapid (typically requiring between 2 and 3\\xa0h), and possesses a similar specificity to existing PCR diagnostic tools. The sensitivity of the assay is comparable to that of an existing PCR-based technique and sufficient for identifying Xcc in symptomatic plant material. The method is easily transferable to diagnosticians without prior experience using FISH.",
            "output": [
                "Do rapid and accurate identification of Xanthomonas citri subspecies citri by fluorescence in situ hybridization?"
            ]
        },
        {
            "id": "task847-5525d32eaabf4e29ae2e746a8caa48ec",
            "input": "The appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive phytocannabinoid, \u2206(9)-tetrahydrocannabinol (\u2206(9)-THC). However, we have previously shown that a cannabis extract devoid of \u2206(9)-THC still stimulates appetite, indicating that other phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour.', 'The objective of the study was to assess the effects of CBG on food intake and feeding pattern microstructure.', 'Male Lister hooded rats were administered CBG (30-120\\xa0mg/kg, per ora (p.o.)) or placebo and assessed in open field, static beam and grip strength tests to determine a neuromotor tolerability profile for this cannabinoid. Subsequently, CBG (at 30-240\\xa0mg/kg, p.o.) or placebo was administered to a further group of pre-satiated rats, and hourly intake and meal pattern data were recorded over 2\\xa0h.', 'CBG produced no adverse effects on any parameter in the neuromotor tolerability test battery. In the feeding assay, 120-240\\xa0mg/kg CBG more than doubled total food intake and increased the number of meals consumed, and at 240\\xa0mg/kg reduced latency to feed. However, the sizes or durations of individual meals were not significantly increased.",
            "output": [
                "Is cannabigerol a novel , well-tolerated appetite stimulant in pre-satiated rats?"
            ]
        },
        {
            "id": "task847-f4a888a82fab4f9c894f0bdd0f902a55",
            "input": "Coronary artery disease (CAD) is a major problem worldwide. As an endothelium-enriched microRNA (miRNA), miR-126 has been reported to serve as a potential biomarker of acute myocardial infarction. However, the relationship between miR-126 and the severity of CAD remains unknown. This study was designed to test whether circulating miR-126 levels are associated with the severity of CAD.', 'The present study enrolled 40 patients who had risk factors for CAD without angiographically significant CAD, and 110 patients presenting with stable angina pectoris, who were validated left main coronary artery disease (LMCA) and/or multi-vessel disease by coronary angiography. The expression levels of plasma miR-126-5p from all enrolled subjects were estimated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the relationships between plasma miR-126-5p levels, number of diseased vessels and the corresponding Synergy between PCI with Taxus and Cardiac surgery (SYNTAX) score were analyzed.', 'The expression of circulating miR-126-5p was affected by some CAD risk factors including aging, dyslipidemia and DM. Furthermore, plasma miR-126-5p levels were significantly down-regulated in CAD patients with multi-vessel disease, higher SYNTAX score, rather than isolated LMCA and low SYNTAX score.",
            "output": [
                "Is plasma MicroRNA-126-5p Associated with the Complexity and Severity of Coronary Artery Disease in Patients with Stable Angina Pectoris?"
            ]
        },
        {
            "id": "task847-1c85ab3ca229400a90671b89a68d13b4",
            "input": "Neurons have a very high energy requirement, and their metabolism is tightly regulated to ensure delivery of adequate substrate to sustain neuronal activity and neuroplastic changes. The mechanisms underlying the regulation of neuronal metabolism, however, are not completely clear.', 'The objective of this study was to investigate the central carbon metabolism in neurons, in order to identify the regulatory pathways governing neuronal anabolism and catabolism.', 'Here we first have applied MS-based endometabolomics to elucidate the metabolic dynamics in cultured hippocampal primary neurons. Using nanoLC-ESI-LTQ Orbitrap MS approach followed by statistical analysis, we measure the dynamics of uniformly labeled ', 'According to non-parametric statistical analysis of metabolic dynamics, in cultured hippocampal neurons, the glycerol phosphate shuttle is active and correlates with the metabolic flux in the pentose phosphate pathway. In the hippocampus, glycerol-3-phosphate biosynthesis was activated in response to long-term potentiation together with the upregulation of glycolysis and the TCA cycle, but was inactive or silenced in basal conditions.",
            "output": [
                "Is biosynthesis of glycerol phosphate associated with long-term potentiation in hippocampal neurons?"
            ]
        },
        {
            "id": "task847-7c6086ac6c5241e2829652e91dbcc3c2",
            "input": "The objective of this study was to assess the prevalence and molecular epidemiology of ESBL-producing Escherichia coli causing healthcare-associated (HCA) and community-associated (CA) bacteraemia of urinary origin (BUO) in Spain.', 'An observational cohort study was conducted at eight hospitals from different Spanish geographical areas (2010-11). BUO episodes (n\\u200a=\\u200a425) were classified as HCA (n\\u200a=\\u200a215) and CA (n\\u200a=\\u200a210), and one blood isolate per episode was collected. Susceptibility testing was performed, ESBLs were screened by double-disc diffusion test and ESBL and OXA-1 genes were characterized (PCR and sequencing). Population structure (phylogenetic groups, XbaI-PFGE and MLST) and ST131 subtyping (PCR) were determined. Virulence genes were detected by PCR and virulence score, profiles and extraintestinal pathogenic E. coli (ExPEC) status calculated.', 'ESBL-producing E. coli prevalence was 9.2% (39/425). ESBL-producing E. coli episodes were significantly associated with HCA-BUO episodes [14% (30/215) versus 4.3% (9/210); P\\u200a=\\u200a0.001]. The highest non-susceptibility proportions corresponded to ciprofloxacin (97.4%), amoxicillin/clavulanate (74.4%), co-trimoxazole (69.2%) and tobramycin (61.5%). Of the 39 ESBL-producing E. coli isolates, 34 produced CTX-M enzymes (21 CTX-M-15, 11 CTX-M-14 and 2 CTX-M-1). Fifteen STs were identified, the B2-ST131 clone being the most prevalent (54%; 21/39). All ST131 isolates were ExPEC and had the highest virulence scores, but they showed less diversity in virulence profiles than other STs. The H30Rx subclone accounted for most ST131 isolates (20/21), co-produced CTX-M-15 (20/20) and OXA-1 (19/20) enzymes and was associated with HCA episodes (16/20).",
            "output": [
                "Is cTX-M-15-H30Rx-ST131 subclone one of the main causes of healthcare-associated ESBL-producing Escherichia coli bacteraemia of urinary origin in Spain?"
            ]
        },
        {
            "id": "task847-1e6fb4567a8e43289965738ff201c8ea",
            "input": "The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy.', 'The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants.', 'The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills.",
            "output": [
                "Do interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy?"
            ]
        },
        {
            "id": "task847-b078f5d602da43aab96812c95f9fda97",
            "input": "High rates of 23S rDNA mutations implicated in macrolide resistance have been identified in Treponema pallidum samples from syphilis patients in many countries. Nonetheless, some clinicians have been reluctant to abandon azithromycin as a treatment for syphilis, citing the lack of a causal association between these mutations and clinical evidence of drug resistance. Although azithromycin resistance has been demonstrated in vivo for the historical Street 14 strain, no recent T. pallidum isolates have been tested. We used the well-established rabbit model of syphilis to determine the in vivo efficacy of azithromycin against 23S rDNA mutant strains collected in 2004 to 2005 from patients with syphilis in Seattle, Wash.', 'Groups of 9 rabbits were each infected with a strain containing 23S rDNA mutation A2058G (strains UW074B, UW189B, UW391B) or A2059G (strains UW228B, UW254B, and UW330B), or with 1 wild type strain (Chicago, Bal 3, and Mexico A). After documentation of infection, 3 animals per strain were treated with azithromycin, 3 were treated with benzathine penicillin G, and 3 served as untreated control groups. Treatment efficacy was documented by darkfield microscopic evidence of T. pallidum, serological response, and rabbit infectivity test.', 'Azithromycin uniformly failed to cure rabbits infected with strains harboring either 23S rDNA mutation, although benzathine penicillin G was effective. Infections caused by wild type strains were successfully treated by either azithromycin or benzathine penicillin G.",
            "output": [
                "Does macrolide Resistance in Treponema pallidum correlate With 23S rDNA Mutations in Recently Isolated Clinical Strains?"
            ]
        },
        {
            "id": "task847-b6422be8a0d3437d8b25c2a31d9f0573",
            "input": "A possible impact of obesity on the risk of thyroid cancer has been postulated in some studies, but it remains controversial.', 'To investigate the association between obesity and differentiated thyroid carcinoma in a population of unselected patients subjected to fine-needle aspiration cytology (FNAC) for thyroid nodules.', 'We retrospectively evaluated the results of FNAC of thyroid nodules in 4,849 patients (3,809 females and 1,040 males; mean age 55.9 \u00b1 14.1 years). Patients were stratified according to their body mass index (BMI). There were 1,876 (38.7%) normal-weight patients (BMI 18-24.9), 1,758 (36.2%) overweight (BMI 25-29.9), 662 (13.7%) grade 1 obese (BMI 30-34.9), 310 (6.4%) grade 2 obese (BMI 35-39.9) and 243 (5.0%) grade 3 obese (BMI >40).', 'The prevalence of suspicious or malignant nodules (Thy4/Thy5) did not differ across the 5 BMI groups, i.e. it was 6.8% in normal-weight patients, 6.3% in overweight patients, 6.3% in grade 1 obese patients, 4.0% in grade 2 obese patients and 4.2% in grade 3 obese patients (p = 0.29). The prevalence of Thy4/Thy5 nodules did not differ when males and females were evaluated separately (p = 0.22 and p = 0.12, respectively). A significant, lower rate of Thy4/5 cytology was observed in female patients with grade 2-3 obesity (odds ratio 0.51; 95% confidence interval 0.284-0.920; p = 0.009).",
            "output": [
                "Does obesity Modify the Risk of Differentiated Thyroid Cancer in a Cytological Series of Thyroid Nodules?"
            ]
        },
        {
            "id": "task847-117ba0e50a6846789815711ddf582cc2",
            "input": "Hypothyroidism is a common endocrine disease associated with increased oxidative stress, increased cardiovascular (CV) risk, CV events and endothelial dysfunction. Endothelial progenitor cells (EPCs) are a well-known marker of CV risk.', 'The aim of this work was to ascertain whether hypothyroidism is associated with lower EPC counts and if treatment with levothyroxine (LT4) or selenium (Se) improves EPC counts compared to placebo.', \"Hypothyrod patients (n = 100) were randomly divided into five groups to receive placebo (group A), LT4 (group B) or Se at doses of 83 \u00b5g (group C), 166 \u00b5g (group D) or 249 \u00b5g (group E) for 3 months. Each group comprised 20 patients: 10 with 'mild' hypothyroidism and 10 with 'severe' hypothyroidism. A healthy control group (group F) with 20 euthyroid subjects was also recruited. Subjects had to be free of CV disease, diabetes and drugs that interfere with EPCs. Anthropometric measurements (height, weight, BMI), blood pressure, fasting lipids and EPC analyses were performed at baseline and after 3 months.\", 'EPC counts were significantly lower in hypothyroid patients compared to controls. EPCs increased after 3 months of treatment with LT4, but not with Se at any dosage. CD133+ and CD34+ EPC counts were negatively correlated with thyroid-stimulating hormone (TSH; r (2) = 0.523, p < 0.01 and r (2) = 0.517, p < 0.01, respectively) and positively correlated with FT4 (r (2) = 0.394, p < 0.01 and r (2) = 0.369, p < 0.01, respectively). TSH and FT4 were the only predictors of EPC counts.",
            "output": [
                "Does levothyroxine but Not Selenium Increases Endothelial Progenitor Cell count in Patients with Hypothyroidism?"
            ]
        },
        {
            "id": "task847-f758b222338444ff98b1cabbb16ef04f",
            "input": "Exogenously administered biglycan (core protein with high-molecular weight glycosaminoglycan chains) has been shown to protect neonatal cardiomyocytes against simulated ischemia/reperfusion injury (SI/R), however, the mechanism of action is not clear. In this study we aimed to investigate, which structural component of biglycan is responsible for its cardiocytoprotective effect and to further explore the molecular mechanisms involved in the cytoprotection.', 'A pilot study was conducted to demonstrate that both native (glycanated) and deglycanated biglycan can attenuate cell death induced by SI/R in a dose-dependent manner in primary neonatal cardiomyocytes isolated from Wistar rats. In separate experiments, we have shown that similarly to glycanated biglycan, recombinant human biglycan core protein (rhBGNc) protects cardiomyocytes against SI/R injury. In contrast, the glycosaminoglycan component dermatan sulfate had no significant effect on cell viability, while chondroitin sulfate further enhanced cell death induced by SI/R. Treatment of cardiomyocytes with rhBGNc reverses the effect of SI/R upon markers of necrosis, apoptosis, mitochondrial membrane potential, and autophagy. We have also shown that pharmacological blockade of Toll-like receptor 4 (TLR4) signaling or its downstream mediators (IRAK1/4, ERK, JNK and p38 MAP kinases) abolished the cytoprotective effect of rhBGNc against SI/R injury. Pretreatment of cardiomyocytes with rhBGNc for 20h resulted in increased Akt phosphorylation and NO production without having significant effect on phosphorylation of ERK1/2, STAT3, and on the production of superoxide. Treatment over 10min and 1h with rhBGNc increased ERK1 phosphorylation, while the SI/R-induced increase in superoxide production was attenuated by rhBGNc. Blockade of NO synthesis also prevented the cardiocytoprotective effect of rhBGNc.",
            "output": [
                "Does the cytoprotective effect of biglycan core protein involve Toll-like receptor 4 signaling in cardiomyocytes?"
            ]
        },
        {
            "id": "task847-72bf5c6aec624fa78a0e543439b28276",
            "input": "Evidence that atopic eczema partly originates in utero is increasing, with some studies linking the risk of developing the condition with aspects of maternal diet during pregnancy. Nicotinamide, a naturally occurring nutrient that is maintained through the dietary intakes of vitamin B3 and tryptophan, has been used in the treatment of some skin conditions including atopic eczema.', 'To examine the relation of maternal serum concentrations of nicotinamide and related tryptophan metabolites to the risk of atopic eczema in the offspring.', 'Within the UK Southampton Women Survey, infantile atopic eczema at ages 6 and 12 months was ascertained (modified UK Working Party Criteria for the Definition of Atopic Dermatitis). Maternal serum levels of kynurenine, kynurenic acid, anthranilic acid, tryptophan, nicotinamide and N1-methylnicotinamide were measured in late pregnancy by mass spectrometry (n = 497) and related to the odds ratio of infantile atopic eczema.', 'Maternal nicotinamide and related metabolite concentrations were not associated with offspring atopic eczema at age 6 months. Higher concentrations of nicotinamide and anthranilic acid were, however, associated with a lower risk of eczema at age 12 months (odds ratios 0.69, 95% CI 0.53-0.91/SD change, P = 0.007 and 0.63, 0.48-0.83, P = 0.001, respectively). The associations were robust to adjustment for potentially confounding variables.",
            "output": [
                "Are higher maternal serum concentrations of nicotinamide and related metabolites in late pregnancy associated with a lower risk of offspring atopic eczema at age 12 months?"
            ]
        },
        {
            "id": "task847-f196ef7e9d99451dbd2dceb7a01ab1d6",
            "input": "Obesity is a cause of preventable morbidity and mortality with an increasing prevalence. Health promoting lifestyle activities maintain or improve an individual's health and in adolescence many habits are configured. The aim of this study was to determine the prevalence of overweight and obesity among adolescents and the relation between obesity and health promoting behaviors.\", \"This is a cross-sectional study including 848 high school students aged 15-17. All students were administered a questionnaire including the Health Promotion Life-Style Profile Scale. Weight and height were measured and body mass index was calculated. Descriptive analysis, Pearson's chi-square test, Kruskal-Wallis and Mann-Whitney U tests, and multivariate logistic regression analysis were used. P < 0.05 was considered statistically significant.\", 'Of the included students, 80.8% (n = 685) had normal ranges of body mass index, 10.1% (n = 86) were overweight, and 9.1% (n = 77) were obese. The Health Promotion Life-Style Profile Scale average score was found to be 126.7 \u00b1 20.4. There was no significant difference between Health Promotion Life-Style Profile Scale and obesity (P = 0.921).",
            "output": [
                "Are health promotion lifestyle profile scores associatedwith obesity in high school students?"
            ]
        },
        {
            "id": "task847-9688ce3c3b7f4e2abcf814288f77cbd5",
            "input": "Serotonergic dysfunction is implicated in depression, psychiatric disorders and suicidal behaviors. The first and rate-limiting step in the synthesis of serotonin is catalyzed by tryptophan hydroxylase (TPH) which is encoded by TPH1 and THP2 genes. Genetic association studies have revealed contradictory results about the effect of the TPH1 A218C (rs1800532) polymorphism on suicidal behavior in different populations.', \"In this study, we investigated A218C polymorphism in 109 suicide attempters and 98 healthy controls. Socio-demographic characteristics of participants were obtained through questionnaire. DNA was extracted from peripheral blood and genotyping was performed by Real Time PCR. Fisher's exact test was used to evaluate the significance of the difference among the independent variables. Hardy-Weinberg equilibrium was tested using Pearson's goodness-of-fit chi-squared test.\", 'The frequency of A allele was significantly higher in suicide attempters than controls (46.33% vs. 35.71%, p=0.0357). However, there were no differences in genotype frequencies of this locus between participants having attempted suicide and controls (p>0.05). Among males, frequencies of CC genotype and C allele were found to be significantly higher in controls (p=0.0125, p=0.0298). With regard to the female subjects and female controls, no significant association was detected between suicidal behavior and genotype/allele frequencies (p>0.05).",
            "output": [
                "Is tPH1 A218 allele associated with suicidal behavior in Turkish population?"
            ]
        },
        {
            "id": "task847-5d936429da5342bb8cf601ee4b10c8f8",
            "input": "Liraglutide improves the metabolic control of diabetic animals after islet transplantation. However, the mechanisms underlying this effect remain unknown. The objective of this study was to evaluate the anti-inflammatory and anti-oxidative properties of liraglutide on rat pancreatic islets in vitro and in vivo.', 'In vitro, rat islets were incubated with 10\\xa0\u03bcmol\u00b7L', 'Islet viability and function were preserved and enhanced with liraglutide treatment. Liraglutide decreased CCL2 and IL-6 secretion and macrophage activation after 12\\xa0h of culture, while IL-10 secretion was unchanged. However, intracellular levels of ROS were increased with liraglutide treatment at 12\\xa0h. This result was correlated with an increase of anti-oxidative capacity. In vivo, liraglutide decreased macrophage infiltration and reduced fasting blood glucose in transplanted rats.",
            "output": [
                "Is improvement of islet graft function using liraglutide correlated with its anti-inflammatory properties?"
            ]
        },
        {
            "id": "task847-a7a3a12ec46042149c8cea379ffd8fb6",
            "input": "Studies have demonstrated a robust association between interpersonal callousness (IC) and the development of severe and chronic conduct problems (CP) in youth. Although children exhibiting IC are also believed to be at particularly high risk for developing psychopathic personality features in adulthood, there is little longitudinal evidence supporting this assumption, particularly after controlling for co-occuring CP severity.', 'This study used data collected on a longitudinal cohort of boys (n\\xa0=\\xa0508), with an oversampling of youth exhibiting elevated conduct problems. Analyses examined the unique and interactive association between latent growth curve trajectories of IC and CP assessed bi-annually from late childhood to early adolescence (~ages 10-13) and features of psychopathy in early adulthood (age\\xa0~\\xa024) assessed using the Psychopathy Checklist - Short Version (PCL:SV; Hart, Cox, & Hare, 1995).', 'Growth curve analysis indicated that initial levels of IC and CP in childhood (~age 10 intercept) both uniquely predicted the development of the interpersonal/affective features of adult psychopathy, and boys with a combination of high initial levels of IC and CP were at particularly high risk for developing the impulsive/antisocial features of the disorder. Boys who exhibited systematic increases in CP from late childhood to early adolescence also demonstrated higher adult psychopathy scores, but changes in IC across this developmental period did not significantly add to the prediction of adult psychopathy.",
            "output": [
                "Do late childhood interpersonal callousness and conduct problem trajectories interact to predict adult psychopathy?"
            ]
        },
        {
            "id": "task847-c58e433b24554ada85be267498c519a6",
            "input": "Bacillus cereus group isolates that produce diarrheal or emetic toxins are frequently isolated from raw milk and, in spore form, can survive pasteurization. Several species within the B. cereus group are closely related and cannot be reliably differentiated by established taxonomical criteria. While B. cereus is traditionally recognized as the principal causative agent of foodborne disease in this group, there is a need to better understand the distribution and expression of different toxin and virulence genes among B. cereus group food isolates to facilitate reliable characterization that allows for assessment of the likelihood of a given isolate to cause a\\xa0foodborne disease.', 'We performed whole genome sequencing of 22 B. cereus group dairy isolates, which represented considerable genetic diversity not covered by other isolates characterized to date. Maximum likelihood analysis of these genomes along with 47 reference genomes representing eight validly published species revealed nine phylogenetic clades. Three of these clades were represented by a single species (B. toyonensis -clade V, B. weihenstephanensis - clade VI, B. cytotoxicus - VII), one by two dairy-associated isolates (clade II; representing a putative new species), one by two species (B. mycoides, B. pseudomycoides - clade I) and four by three species (B. cereus, B. thuringiensis, B. anthracis - clades III-a, b, c and IV). Homologues of genes encoding a principal diarrheal enterotoxin (hemolysin BL) were distributed across all, except the B. cytotoxicus clade. Using a lateral flow immunoassay, hemolysin BL was detected in 13 out of 18 isolates that carried hblACD genes. Isolates from clade III-c (which included B. cereus and B. thuringiensis) consistently did not carry hblACD and did not produce hemolysin BL. Isolates from clade IV (B. cereus, B. thuringiensis) consistently carried hblACD and produced hemolysin BL. Compared to others, clade IV was significantly (p\\u2009=\\u20090.0001) more likely to produce this toxin. Isolates from clade VI (B. weihenstephanensis) carried hblACD homologues, but did not produce hemolysin BL, possibly due to amino acid substitutions in different toxin-encoding genes.",
            "output": [
                "Is production of hemolysin BL by Bacillus cereus group isolates of dairy origin associated with whole-genome phylogenetic clade?"
            ]
        },
        {
            "id": "task847-2aadaeb3c7da40bfa890803393e2aee6",
            "input": "Serum uric acid (SUA) has been associated to incident hypertension and increased risk of cardiovascular diseases.', 'Among the 2191 subjects enrolled during the last population survey of the Brisighella Heart Study, we identified 146 new cases of arterial hypertension and 394 treated but uncontrolled hypertensive patients with different levels of SUA. Their hemodynamic characteristics have been compared with those of age- and sex-matched normotensive (N. 324) and controlled hypertensive (N. 470) subjects. Then, by logistic regression analysis, we evaluated which factors were associated with a worse BP control under pharmacological treatment.', 'SUA levels were significantly higher in untreated hypertensive and uncontrolled hypertensive patients when compared to normotensives and controlled hypertensive patients. Pulse wave velocity (PWV) was significantly higher (p<0.001) in undiagnosed and uncontrolled hypertensive patients, while controlled hypertensive patients had PWV values comparable to normotensive controls. A similar trend has been observed for the augmentation index (AI). A worse BP control was associated with SUA levels (OR 1277, 95% CI 1134-1600 per mg/dL), AI (OR 1066, 95%CI 1041-1092 per unit), and PWV (OR 1201, 95% CI 1089-1423, per m/s), but not with age, body mass index, nor estimated glomerular filtration rate.",
            "output": [
                "Is high serum uric acid associated to poorly controlled blood pressure and higher arterial stiffness in hypertensive subjects?"
            ]
        },
        {
            "id": "task847-e13617b2d5fc46d9bb4a3107d3450a63",
            "input": "KRAS-mutant lung adenocarcinoma is among the most common cancer entities and, in advanced stages, typically displays poor prognosis due to acquired resistance against chemotherapy, which is still largely based on cisplatin-containing combination regimens. Mechanisms of cisplatin resistance have been extensively investigated, and ERCC1 has emerged as a key player due to its central role in the repair of cisplatin-induced DNA lesions. However, clinical data have not unequivocally confirmed ERCC1 status as a predictor of the response to cisplatin treatment. Therefore, we employed an autochthonous mouse model of Kras-driven lung adenocarcinoma resembling human lung adenocarcinoma to investigate the role of Ercc1 in the response to cisplatin treatment. Our data show that Ercc1 deficiency in Tp53-deficient murine lung adenocarcinoma induces a more aggressive tumor phenotype that displays enhanced sensitivity to cisplatin treatment. Furthermore, tumors that relapsed after cisplatin treatment in our model develop a robust etoposide sensitivity that is independent of the Ercc1 status and depends solely on previous cisplatin exposure. Our results provide a solid rationale for further investigation of the possibility of preselection of lung adenocarcinoma patients according to the functional ERCC1- and mutational TP53 status, where functionally ERCC1-incompetent patients might benefit from sequential cisplatin and etoposide chemotherapy.",
            "output": [
                "Does ercc1 Deficiency promote Tumorigenesis and Increases Cisplatin Sensitivity in a Tp53 Context-Specific Manner?"
            ]
        },
        {
            "id": "task847-c2a6bf1613d64396bf8a219626a5358a",
            "input": "To investigate whether autophagy can be induced by 1, 4-benzoquinone (1, 4-BQ) in HL60 cells, as well as the role of reactive oxygen species (ROS) in induced autophagy.', 'In order to determine a suitable 1, 4-BQ treatment concentration for autophagy detection in HL60 cells, the cell vitality were examined by CCK8 assay. Logarithmic-growth-phased cells were divided into control group, 1, 4-BQ group (10\u03bcmol/L 1, 4-BQ, 24 h) , NAC group (antioxidant n-acetyl cysteine, 5mmol/L, 24 h) and the 1, 4-BQ+NAC group (5 mmol/L NAC were preincubated for 1h prior to the treatment with 10 \u03bcmol/L 1, 4-BQ for 24 h). The autophagic acidic vesicle were inspected by acridine orange staining, LC3 were detected by immunofluorescence staining, and expressions of LC3 and Beclin1 were quantitatively detected by Western blot.', 'The results from cell viability test indicated that 1, 4-BQ exhibited a dose-dependent toxicity to HL60 cells. Compared with control group.the cell viability in 20.0\u300140.0\u03bcmol/L concentration were decreased obviously, and the differences had statistical significance (P<0.05). Compare with contrd group acidic vesicle, LC3II, LC3II/LC3I and Beclin1 protein expressions were increased in 1, 4-BQ group, after both respectively 12.4% and 27%, the differences had statistital significance. While 1, 4-BQ+NAC group was observed that acidic vesicle, LC3 and Beclin1 protein level were markedly lower than 1, 4-BQ group, after both decreased 12.6% and 22.6% respectively, both the difference were statistically significant (P<0.05).",
            "output": [
                "Do [ Benzoquinone induce autophagy in HL60 cells and the role of reactive oxygen species in induced autophagy ]?"
            ]
        },
        {
            "id": "task847-2a5f7c435b1d40f0b059b637b07aed79",
            "input": "We tested the hypothesis that collagen cross-linking (CXL) could be used to promote adhesion in mock corneal grafts.', \"Donated human corneal tissue underwent epithelial debridement and was cut into sections measuring 4mm\u00d73mm. Paired sections were sutured together with 10-0 vicryl, forming mock corneal grafts. Looped 6-0 sutures were placed at each end to facilitate tension measurement. Mock grafts underwent CXL before being cultured for 2days in Eagle's MEM culture medium. Control mock grafts did not undergo CXL treatment before culture. Tissue was obtained from 4 donors and a maximum of 2 controls and 2 treated grafts was obtained from each donor. Following the culture period, the 10-0 sutures were cut. The mock grafts were mounted on force transducers and were put under increasing tension until eventually the sections were pulled apart.\", 'The mean applied stress required to generate graft failure was calculated for all mock grafts\u00b1standard error of the mean. In the control group 0.236\u00b10.09mPa of applied stress was required to cause graft failure, in comparison to 0.691\u00b10.12mPa in the treated group. A paired t-test showed this result to be significant, (p=0.0087).",
            "output": [
                "Does collagen cross-linking treatment increase adhesion in mock corneal grafts?"
            ]
        },
        {
            "id": "task847-effa0f63733644218e02e202c9e77838",
            "input": "To determine the effectiveness of submandibular salivary gland Botulinum Toxin Type-A (BTX-A) injection in the treatment of drooling in children with varying degrees of neurological dysfunction.', 'A retrospective review of pre- and post-procedure drooling frequency and severity scores of patients receiving BTX-A between January 2008 and January 2013. Stratification to different subgroups of neurological impairment was performed according to Gross Motor Function Classification System (GMFCS) score. Drooling severity was assessed using Thomas-Stonell and Greenberg symptom questionnaires administered at time of initial consultation and 3 months after treatment.', '48 sets of BTX-A injections in 26 patients with an average age of 9.45 years (range 7 months-18 years) were included in the study. Marked improvement in drooling was seen in 60.4% of patients, a marginal or brief improvement was seen in 20.8% and there was no improvement in 18.8%. No adverse events were reported following any of the BTX-A injections. BTX-A was safe and effective in the eight patients with pre-existing swallowing dysfunction. Subsequent drooling surgery was performed in 15 (57.7%) of the cohort, all 15 patients responded to BTX-A injections. In patients with Cerebral Palsy, there was no correlation between the severity of the neurological dysfunction as measured by the Gross Motor Function Classification System (GMFCS) score and the response to BTX-A treatment.",
            "output": [
                "Are botulinum toxin injections for chronic sialorrhoea in children effective regardless of the degree of neurological dysfunction : A single tertiary institution experience?"
            ]
        },
        {
            "id": "task847-af83f339681147eca57be0824039ea55",
            "input": "Nicotinamide adenine dinucleotide (NAD(+)) and its phosphorylated form (NADP(+)) are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating cellular metabolism and homeostasis. Thus, supplementation with NAD(+) and NADP(+) precursors emerged as a promising strategy to gain many and multifaceted health benefits. In this proof-of-concept study, we sought to investigate whether chronic nicotinamide riboside administration (an NAD(+) precursor) affects exercise performance.', 'Eighteen Wistar rats were equally divided in two groups that received either saline vehicle or nicotinamide riboside at a dose of 300\\xa0mg/kg body weight/day for 21\\xa0days via gavage. At the end of the 21-day administration protocol, both groups performed an incremental swimming performance test.', 'The nicotinamide riboside group showed a tendency towards worse physical performance by 35\\xa0% compared to the control group at the final 10\\xa0% load (94\\u2009\u00b1\\u200953\\xa0s for the nicotinamide riboside group and 145\\u2009\u00b1\\u200959\\xa0s for the control group; P\\u2009=\\u20090.071).",
            "output": [
                "Does the NAD ( + ) precursor nicotinamide riboside decrease exercise performance in rats?"
            ]
        },
        {
            "id": "task847-e3cdc5b1b8ac42f49d9a79ebd3819d98",
            "input": "Chromatin modifications such as DNA methylation are targeted to transposable elements by small RNAs in a process termed RNA-directed DNA methylation (RdDM). In plants, canonical RdDM functions through RNA polymerase IV to reinforce pre-existing transposable element silencing. Recent investigations have identified a \"non-canonical\" form of RdDM dependent on RNA polymerase II expression to initiate and re-establish silencing of active transposable elements. This expression-dependent RdDM mechanism functions through RNAi degradation of transposable element mRNAs into small RNAs guided by the RNA-dependent RNA polymerase 6 (RDR6) protein and is therefore referred to as RDR6-RdDM.', 'We performed whole-genome MethylC-seq in 20 mutants that distinguish RdDM mechanisms when transposable elements are either transcriptionally silent or active. We identified a new mechanism of expression-dependent\\xa0RdDM, which functions through DICER-LIKE3 (DCL3) but bypasses the requirement of both RNA polymerase IV and RDR6 (termed DCL3-RdDM). We found that RNA polymerase II expression-dependent forms of RdDM function on over 20\\xa0% of transcribed transposable elements, including the majority of full-length elements with all of the domains required for autonomous transposition. Lastly, we find that RDR6-RdDM preferentially targets long transposable elements due to the specificity of primary small RNAs to cleave full-length mRNAs.",
            "output": [
                "Are full-length autonomous transposable elements preferentially targeted by expression-dependent forms of RNA-directed DNA methylation?"
            ]
        },
        {
            "id": "task847-c348ef9463074113baf9f27360873ee8",
            "input": "Class I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown.', \"Four isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2\u03b1 knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student's T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival.\", 'Our analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2\u03b1 is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ER\u03b1) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated \u03b1-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset.",
            "output": [
                "Do hDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma?"
            ]
        },
        {
            "id": "task847-a83913439f6249fd94ac4f97b35e8aec",
            "input": "Skin grafting is needed for traditional auricular reconstruction. As the skin grafts contract, the postoperative framework is distorted. This leads to a decrease in the auriculocephalic angle. The objective of this study was to test a new method to cover the reconstructive framework by using three skin flaps and a larger tissue expander than that normally used. This may reduce the distortion of the reconstructed ear and create a well-shaped auriculocephalic angle.', 'A large expander was inserted in the postauricular mastoid area. Three expanded flaps were then created to cover the anterior and posterior frameworks, with separate mastoid coverage. By measuring the height and angle at three different points on the reconstructed ear and comparing them with the contralateral normal ear, a system for measuring the auriculocephalic angle was established.', \"The surface of the framework and the mastoid area were covered by three flaps developed from one large tissue expander. The appearance of the reconstructed ears was similar to that of the normal side by the patient's 6- to 12-month follow-up. The difference in the distance at the three points between the reconstructed and normal sides after the three-flap reconstruction was less than that following traditional reconstruction (p\\xa0<\\xa00.05). The variation in the angle measured at these three points in the three-flap group was also much smaller than that in the traditional group (p\\xa0<\\xa00.01).",
            "output": [
                "Does auricular reconstruction using a novel three-flap technique improve the auriculocephalic angle?"
            ]
        },
        {
            "id": "task847-ba61a8a44adb409b8ba144bc226ebff4",
            "input": "Measuring quality of care is essential to improve primary care. Quality of primary care for patients is usually assessed by patient satisfaction questionnaires. However, patients may not be able to judge quality of care without also reflecting their perception of the environment. We determined the effect that redesigning a primary care office had on patient satisfaction. We hypothesized that renovating the interior would make patients more satisfied with the quality of medical care.', 'We performed a Pretest-Posttest analysis in a recently renovated single-practice primary care office in Grenchen, Switzerland. Before and after renovation, we distributed a questionnaire to assess patient satisfaction in four domains. We chose a Likert scale (1\\u2009=\\u2009very poor to 6\\u2009=\\u2009very good), and 12 quality indicators, and included two consecutive samples of patients presenting at the primary care office before (n\\u2009=\\u2009153) and after (n\\u2009=\\u2009153) interior design renovation.', 'Response rate was high (overall 85\\xa0%). The sample was similar to the enlisted patient collective, but the sample population was older (60\\xa0years) than the collective (52\\xa0years). Patient satisfaction was higher for all domains after the office was renovated (p\\u2009<\\u20090.01-0.001). Results did not change when we included potential confounders in the multivariable model (p\\u2009<\\u20090.01).",
            "output": [
                "Is patient satisfaction biased by renovations to the interior of a primary care office : a pretest-posttest assessment?"
            ]
        },
        {
            "id": "task847-dba6107a9a884ec99edc8e90d9339a4d",
            "input": "Prostate cancer (PCa) is a leading cause of cancer-related death in men, which emphasizes the need for novel therapeutic approaches. Targeting microRNA (miRNA) has been considered as a therapeutic strategy against cancers. Human miR-204-5p potentially targeting BCL2 has been reported to be downregulated in various cancers. We hypothesized that miR-204-5p overexpression induces cancer cell apoptosis by repressing BCL2 expression.', 'A vector harboring mature miR-204-5p was constructed and delivered into human PCa cells. The expression level of miR-204-5p was determined by miRNA quantitative polymerase chain reaction (QPCR). Luciferase reporter assays were performed to verify the function of mature miR-204-5p and its direct binding to BCL2 transcripts. The expression levels of BCL-2 messenger RNA (mRNA) and protein samples were measured by QPCR and Western blot, respectively. Cell viability was detected by WST-1 assays. Induction of apoptosis was determined by increased levels of cleavage caspase 3 and caspase 3/7 activity.', \"The expression levels of miR-204-5p were downregulated in PCa cells compared with normal prostate epithelial cells. Transfection of pSM-204 resulted in up to 6.2-fold higher expression of miR-204-5p when compared with pSM control. The mRNA levels of several potential target genes of miR-204-5p were decreased in pSM-204-transfected PC3 and Rv1 cells. BCL2 mRNA and protein expression decreased in miR-204-5p-transfected cells, which led to cytochrome C release from mitochondria. It subsequently increased cleaved caspase 3 and caspase 3/7 activities and reduced cell viability. Cotransfection of a reporter vector harboring the BCL2 3'-untranslated region to compete with endogenous transcripts partially rescued miR-204-5p-induced apoptosis.",
            "output": [
                "Does tumor suppressor miRNA-204-5p promote apoptosis by targeting BCL2 in prostate cancer cells?"
            ]
        },
        {
            "id": "task847-5bf4bbb7b188413082d5e411fb2e2d93",
            "input": "The role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM).', 'The study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 \u00b1 5.3 years) without clinical symptoms of ischemic heart disease. The control group consisted myocardial fragments taken from 10 male heart valve and pulmonary artery donors with diagnosed cerebral death (age 40 \u00b1 2.3 years). BRCA1 was detected immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity of BRCA1 expression was semiquantitatively assessed for cardiocytes, small vessels including capillaries, and interstitial cells. The significances between groups were estimated using the Mann-Whitney U test.', 'All IDCM cases were positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes showed very intense staining and typical cardiomyopathic cardiocytes were stained weakly forming mosaic. Control cases showed weak-to-moderate uniform staining. Intensity of staining was significantly higher in IDCM cardiocytes, whereas small vessels and interstitial were stained similarly in both groups.",
            "output": [
                "Does bRCA1 reflect Myocardial Adverse Remodeling in Idiopathic Dilated Cardiomyopathy?"
            ]
        },
        {
            "id": "task847-f929f2a4ecee4a6cbcd952d5e887c8e5",
            "input": "The characteristic ease of use, rapid time to result, and low cost of malaria rapid diagnostic tests (RDTs) promote their widespread use at the point-of-care for malaria detection and surveillance. However, in many settings, the success of malaria elimination campaigns depends on point-of-care diagnostics with greater sensitivity than currently available RDTs. To address this need, a sample preparation method was developed to deliver more biomarkers onto a malaria RDT by concentrating the biomarker from blood sample volumes that are too large to be directly applied to a lateral flow strip.', 'In this design, Ni-NTA-functionalized magnetic beads captured the Plasmodium falciparum biomarker HRPII from a P. falciparum D6 culture spiked blood sample. This transfer of magnetic beads to the RDT was facilitated by an inexpensive 3D-printed apparatus that aligned the sample tube with the sample deposition pad and a magnet beneath the RDT. Biomarkers were released from the bead surface onto the lateral flow strip using imidazole-spiked running buffer. Kinetics of HRPII binding to the Ni-NTA beads as a function of blood sample volume were explored prior to determining the effect of the proposed method on the limit of detection of Paracheck RDTs.', 'More than 80\\xa0% of HRPII biomarkers were extracted from blood sample volumes ranging from 25 to 250\\xa0\u00b5L. The time required to reach 80\\xa0% binding ranged from 5 to 60\\xa0min, depending on sample volume. Using 250\\xa0\u03bcL of blood and a 30-min biomarker binding time, the limit of detection of the Paracheck Pf RDT brand was improved by 21-fold, resulting in a limit of detection below 1 parasite/\u03bcL.",
            "output": [
                "Does direct transfer of HRPII-magnetic bead complexes to malaria rapid diagnostic tests significantly improve test sensitivity?"
            ]
        },
        {
            "id": "task847-02ece490395348f9a3f8bb39b528ce4f",
            "input": "The aim of this study was to test the efficacy of aminolevulinic acid-mediated photodynamic therapy (PDT) against the human osteosarcoma cell line MG-63.', 'Osteosarcoma is the most common type of primary malignant bone tumor diagnosed in the United States among adolescents and children. Treatments for osteosarcoma often result in diminished limb use or amputation. Because ALA-mediated PDT exhibits dual specificity in the context of tumor killing, this therapy could represent a less invasive, but effective, treatment for this disease.', 'To assess ALA dark toxicity in MG-63 cells, cells were incubated with varying concentrations of ALA, and cell viability was determined by crystal violet assay. Protoporphyrin IX (PpIX) accumulation was assessed subsequent to ALA incubation at various concentrations using spectrofluorometry. Cell death subsequent to ALA-PDT was determined by illuminating cells at a wavelength of 635\\u2009nm at various light intensities subsequent to ALA incubation. Cell viability was assessed using the MTT assay.', 'ALA dark toxicity was observed only at the highest concentrations of 2, 5, and 10\\u2009mM. Maximal PpIX concentration was observed at 0.5 and 1\\u2009mM ALA, subsequent to a 24-h incubation. Maximal cell death with minimal light toxicity was observed at 0.5 and 1\\u2009mM ALA after illumination with 0.6 and 3\\u2009J/cm(2) light.",
            "output": [
                "Does aminolevulinic Acid-Mediated Photodynamic Therapy cause Cell Death in MG-63 Human Osteosarcoma Cells?"
            ]
        },
        {
            "id": "task847-ea6e2c4dd5514b2a9b2ef57224618825",
            "input": "In this study, we investigated the direct effect of C5a overexpression on atherosclerosis.', 'A recombinant adenovirus expressing mouse C5a (Ad-C5a) was constructed and injected intravenously into ApoE-/- mice. After 12 weeks of a high-fat diet, Ad-C5a injection produced more extensive lesions than control adenovirus, and its proathrosclerotic role was significantly blocked by C5a receptor antagonist. Immunohistochemical analysis showed enhanced macrophage infiltration in atherosclerotic regions with C5a overexpression. Trans-well assay revealed C5a receptor-dependent chemotaxis of C5a to macrophages. Furthermore, Ad-C5a overexpression promoted foam cell formation and lipid deposition but reduced collagen content. In addition, with Ad-C5a overexpression, the serum levels of interleukin 6 and tumor necrosis factor \u03b1 were upregulated.",
            "output": [
                "Does overexpression of complement component C5a accelerate the development of atherosclerosis in ApoE-knockout mice?"
            ]
        },
        {
            "id": "task847-c9af851ec1364a188bd54cc3b4c36a20",
            "input": "The circadian clocks are internal timing mechanisms that drive \u223c24-hour rhythms in a tissue-specific manner. Many aspects of the physiology of the intervertebral disc (IVD) show clear diurnal rhythms. However, it is unknown whether IVD tissue contains functional circadian clocks and if so, how their dysregulation is implicated in IVD degeneration.', 'Clock gene dynamics in ex vivo IVD explants (from PER2:: luciferase (LUC) reporter mice) and human disc cells (transduced with lentivirus containing Per2::luc reporters) were monitored in real time by bioluminescence photon counting and imaging. Temporal gene expression changes were studied by RNAseq and quantitative reverse transcription (qRT)-PCR. IVD pathology was evaluated by histology in a mouse model with tissue-specific deletion of the core clock gene Bmal1.', 'Here we show the existence of the circadian rhythm in mouse IVD tissue and human disc cells. This rhythm is dampened with ageing in mice and can be abolished by treatment with interleukin-1\u03b2 but not tumour necrosis factor \u03b1. Time-series RNAseq revealed 607 genes with 24-hour patterns of expression representing several essential pathways in IVD physiology. Mice with conditional knockout of Bmal1 in their disc cells demonstrated age-related degeneration of IVDs.",
            "output": [
                "Does the intervertebral disc contain intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration?"
            ]
        },
        {
            "id": "task847-ffb7432cea354ca2848e1efdff37c854",
            "input": "Previously, we found an 11-gene signature could predict pelvic lymph node metastasis (PLNM), and WNT2 is one of the key genes in the signature. This study explored the expression and underlying mechanism of WNT2 in PLNM of cervical cancer.', 'WNT2 expression level in cervical cancer was detected using western blotting, quantitative PCR, and immunohistochemistry. Two WNT2-specific small interfering RNAs (siRNAs) were used to explore the effects of WNT2 on invasive and metastatic ability of cancer cells, and to reveal the possible mechanism of WNT2 affecting epithelial-mesenchymal transition (EMT). The correlation between WNT2 expression and PLNM was further investigated in clinical cervical specimens.', 'Both WNT2 mRNA and protein expression was upregulated in cervical cancer. High WNT2 expression was significantly associated with tumor size, lymphovascular space involvement, positive parametrium, and most importantly, PLNM. PLNM and WNT2 expression were independent prognostic factors for overall survival and disease-free survival. WNT2 knockdown inhibited SiHa cell motility and invasion and reversed EMT by inhibiting the WNT2/\u03b2-catenin pathway. WNT2 overexpression in cervical cancer was associated with \u03b2-catenin activation and induction of EMT, which further contributed to metastasis in cervical cancer.",
            "output": [
                "Does wNT2 promote Cervical Carcinoma Metastasis and Induction of Epithelial-Mesenchymal Transition?"
            ]
        },
        {
            "id": "task847-85f470505c0e4e888c21e1866241490b",
            "input": "To discriminate non-proliferative diabetic retinopathy (NPDR) patients from healthy controls by fluorescence lifetime imaging ophthalmoscopy (FLIO).', 'A prototype FLIO (Heidelberg-Engineering, Heidelberg, Germany) was used to examine the retina of 33 patients and 28 controls. As increased fluorescence of the diabetic lens is known, the lenses of 34 patients and 24 controls were investigated as well. Time-resolved decay was detected in two spectral channels (ch1: 498-560\\xa0nm, ch2: 560-720\\xa0nm) and approximated by a series of three exponential functions yielding in lifetimes (\u03c4', 'Significant differences between patients and controls were found for all fundus lifetime components (\u03c4",
            "output": [
                "Are fundus autofluorescence lifetimes increased in non-proliferative diabetic retinopathy?"
            ]
        },
        {
            "id": "task847-4c0de10522fd4676968681a819739459",
            "input": "Natriuretic peptide (NP) levels are routinely employed as useful diagnostic and prognostic tools in the evaluation of patients with heart failure (HF). As hospitalization is the major consumer of healthcare resources, the prognostic power of admission NPs with regard to the duration of hospitalization deserves further investigation.', 'We assessed retrospectively the association between NP values sampled shortly following unplanned admission and the duration of hospitalization in 2978 patients admitted to a cardiology department. Duration of hospitalization (hours) and survival were determined by interrogation of the electronic medical records system. Associations with peptide levels were estimated using regression models and receiver operating characteristic (ROC) analysis. The results demonstrate a significant positive relationship between NP levels and the duration of hospitalization, after adjusting for age (P < 0.001). The median duration of hospitalization for the lowest BNP and NT-proBNP quintiles were 80 and 97 h, respectively, vs. 224.5 and 236 h for the highest quintiles. Using cut-off levels of 115 pmol/L for BNP and 390 pmol/L for NT-proBNP, the peptides have a positive predictive value of 78% and 85% for a stay >4 days. During follow-up, NP levels were strongly predictive of all-cause mortality.",
            "output": [
                "Do natriuretic peptide levels taken following unplanned admission to a cardiology department predict the duration of hospitalization?"
            ]
        },
        {
            "id": "task847-6bb63c8f2d8d4690824ff032cd2951af",
            "input": "A small percentage of neonates with sacrococcygeal teratoma die shortly after birth from hemorrhagic complications. The incidence of and risk factors associated with hemorrhagic mortality are unknown. In this multicenter study we determined the incidence of early death in neonates born with SCT and evaluated potential risk factors for hemorrhagic mortality.', '235 children with SCT treated from 1970 to 2010 in the Netherlands were retrospectively included. The following candidate risk factors for hemorrhagic mortality were examined: sex, prematurity, Altman type, tumor volume, tumor histology, necessity of emergency operation and time of diagnosis.', 'Eighteen patients (7.7%) died at a median age of 163.5days (range 1.7-973days). Nine patients died of a malignancy. Nine others (3.8%) died postnatally (age 1-27days), six even within two days after birth. In seven of these nine patients death was related to tumor-hemorrhage and/or circulatory failure. Risk factors for hemorrhagic mortality were prematurity, tumor volume>1000cm",
            "output": [
                "Is hemorrhage the most common cause of neonatal mortality in patients with sacrococcygeal teratoma?"
            ]
        },
        {
            "id": "task847-381d8065e1474f1d9ab56a11293c30c3",
            "input": "Allergic airway inflammation is triggered by allergen exposure through several steps including release of IL-33, which promotes cytokine (IL-5, IL-13) production by type 2 innate lymphoid cells (ILC2s). MicroRNA (miR)-155 has recently been described to regulate adaptive responses in allergic inflammation. However, the role of miR-155 in the regulation of ILC2s remains unexplored.', 'We sought to elucidate the contribution of miR-155 in ILC2 expansion using experimental murine models of allergic airway inflammation.', 'To determine the role of miR-155 in the regulation of ILC2s in allergic airway inflammation, miR-155 deficient (miR-155', 'miR-155 was 10-fold upregulated in WT-derived ILC2s in response to IL-33. Furthermore, miR-155",
            "output": [
                "Is microRNA-155 a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation?"
            ]
        },
        {
            "id": "task847-2ed8a20a2a2444b6809da82cd110fdc8",
            "input": "Continuous exposure to particulate air pollution (PM) is a serious worldwide threat to public health as it coherently links with increased morbidity and mortality of cardiorespiratory diseases (CRD), and of type 2 diabetes (T2D). Extracellular vesicles (EVs) are circular plasma membrane fragments released from human cells that transfer microRNAs between tissues. In the present work it was explored the hypothesis that EVs with their encapsulated microRNAs (EVmiRNAs) contents might mediate PM effects by triggering key pathways in CRD and T2D.', 'Expression of EVmiRNAs analyzed by real-time PCR was correlated with oxidative stress, coagulation and inflammation markers, from healthy steel plant workers (n=55) with a well-characterized exposure to PM and PM-associated metals. All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways regulated by PM-associated EVmiRNAs.', 'Increased expression in 17 EVmiRNAs is associated with PM and metal exposure (p<0.01). Mir-196b that tops the list, being related to 9 different metals, is fundamental in insulin biosynthesis, however three (miR-302b, miR-200c, miR-30d) out of these 17 EVmiRNAs are in turn also related to disruptions (p<0.01) in inflammatory and coagulation markers.",
            "output": [
                "Does extracellular vesicle-driven information mediate the long-term effects of particulate matter exposure on coagulation and inflammation pathways?"
            ]
        },
        {
            "id": "task847-a32fd1aaa4f045948a23fef25585ab3e",
            "input": "MRI of tissues with rapid transverse relaxation can be performed efficiently using the zero echo time (ZTE) technique. At high bandwidths leading to large relative initial radiofrequency (RF) dead times, the method becomes increasingly sensitive to artifacts related to signal stemming from outside the field of view, particularly from the RF coils. Therefore, in this work, a birdcage coil was designed that is virtually free of 1H signal.', 'A transmit-receive birdcage RF coil for MRI of joints at 7T was designed by rigorously avoiding materials containing 1H nuclei, by using purely mechanical connections without glue, and by spoiling of unwanted signal by application of ferromagnetic materials. The coil was tested for residual 1H signal using ZTE phantom and in vivo joint imaging.', 'In standard ZTE imaging, no 1H signal was detected above noise level. Only at extreme averaging, residual signal was observed close to conductors associated with 1H-containing molecules at adjacent glass surfaces. Phantom images with dead times up to 3.8 Nyquist dwells were obtained with only negligible background artifacts. Furthermore, high-quality ZTE images of human joints were acquired.",
            "output": [
                "Do a virtually 1H-free birdcage coil for zero echo time MRI without background signal?"
            ]
        },
        {
            "id": "task847-2702ba681a7f4c1db4f06c27d1607dcc",
            "input": "To describe the findings of enhanced depth imaging (EDI) optical coherence tomography (OCT) of the lamina cribrosa (LC) in glaucoma and pachychoroid spectrum diseases associated with peripapillary retinoschisis.', 'Retrospective, observational case series.', 'A total of 16 patients from 1 institution.', 'Detailed medical case histories, optic disc and retinal imaging with EDI using the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany), and clinical course were reviewed for patients with peripapillary retinoschisis without a known predisposing condition.', 'Clinical features and findings of the EDI OCT.', 'Among the 16 eyes with peripapillary retinoschisis that had abnormal findings on EDI of the LC, 8 had glaucoma and 8 had pachychoroid spectrum diseases, including chronic central serous chorioretinopathy (CSC) (6 eyes), small pigment epithelium detachment (1 eye), and polypoidal choroidal vasculopathy (PCV) (1 eye). The abnormal LC findings were central or peripheral focal LC defects in eyes with glaucoma and LC disinsertions or peripheral focal LC defects in eyes with pachychoroid spectrum diseases. Central LC defects were related to inner layer retinoschisis, whereas LC disinsertions and peripheral LC defects were related to outer layer retinoschisis. The peripapillary retinoschisis did not show a topographic association with the underlying chronic CSC- or PCV-associated lesions. In 6 treated eyes with pachychoroid, peripapillary retinoschisis resolved along with subretinal fluid after anti-vascular endothelial growth factor injection in 4 eyes, whereas retinoschisis persisted after the resolution of subretinal fluid in 2 eyes.",
            "output": [
                "Do alterations of the Lamina Cribrosa Are Associated with Peripapillary Retinoschisis in Glaucoma and Pachychoroid Spectrum Disease?"
            ]
        },
        {
            "id": "task847-0f5b50b0653d4a3cb1fb13717578bc97",
            "input": "Sophora flavescens Aiton (Radix Sophorae Flavescentis, Kushen) is used in traditional Chinese medicine to treat chronic hepatitis B (CHB), and has the ability to clear heat and dampness from the body. Oxymatrine is one of the major bioactive compounds extracted from Sophora flavescens Aiton and constitutes more than 90% of the oxymatrine injection commonly used for CHB treatment in clinics in China.', 'We aim to analyze the protein binding target of oxymatrine in treating CHB by screening a T7 phage display cDNA library of human CHB and examine the biochemistry of protein-ligand binding between oxymatrine and its ligands.', 'A T7 phage cDNA library of human CHB was biopanned by affinity selection using oxymatrine as bait. The interaction of oxymatrine with its candidate binding protein was investigated by affinity assay, molecular docking, Isothermal Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR).', 'A library of potential oxymatrine binding peptides was generated. Ubiquinol-cytochrome c reductase binding protein (UQCRB) was one of the candidate binding proteins of oxymatrine. UQCRB-displaying T7 phage binding numbers in the oxymatrine group were significantly higher than that in the control group, biotin group, and matrine group (p<0.05 or p<0.01). Three-dimensional structure modeling of the UQCRB with oxymatrine showed that their binding interfaces matched and oxymatrine inserted into a deeper pocket of UQCRB, which mainly involved amino acid residues Tyr21, Arg33, Tyr83, Glu84, Asp86, Pro88, and Glu91. The binding affinity constant (Kb) from SPR was 4.2mM. The Kb from ITC experiment was 3.9mM and stoichiometry was fixed as 1, which fit very well with the result of SPR. The binding of oxymatrine to UQCRB was driven by strong enthalpy forces such as hydrogen bonds and polar interactions as the heat released was about 157kcal/mol and \u0394G was less than zero.",
            "output": [
                "Do identification of UQCRB as an oxymatrine recognizing protein using a T7 phage display screen?"
            ]
        },
        {
            "id": "task847-ec09f3daa54346f681461ae6609e3cea",
            "input": "Are low vitamin D levels linked with semen quality and sex steroids in infertile men?",
            "output": [
                "Are vitamin D deficiency and low ionized calcium linked with semen quality and sex steroid levels in infertile men?"
            ]
        },
        {
            "id": "task847-b3b6a198ebe845529e318634de6412f4",
            "input": "Hemoglobins (Hbs) are evolutionarily conserved heme-containing metallo-proteins of the Globin protein family that harbour the characteristic \"globin fold.\" Hemoglobins have been functionally diversified during evolution and their usual property of oxygen transport is rather a recent adaptation. Drosophila genome possesses three globin genes (glob1, glob2, and glob3), and we have reported earlier that adequate expression of glob1 is required for various aspects of development, as well as to regulate the cellular level of reactive oxygen species (ROS). The present study illustrates the explicit role of Drosophila globin1 in progression of oogenesis.', 'We demonstrate a dynamic expression pattern of glob1 in somatic and germ cell derivatives of developing egg chambers during various stages of oogenesis, which largely confines around the F-actin-rich cellular components. Reduced expression of glob1 leads to various types of abnormalities during oogenesis, which were primarily mediated by the inappropriately formed F-actin-based cytoskeleton. Our subsequent analysis in the somatic and germ line clones shows cell autonomous role of glob1 in the maintenance of the integrity of F-actin-based cytoskeleton components in the somatic and germ cell derivatives.",
            "output": [
                "Is drosophila glob1 required for the maintenance of cytoskeletal integrity during oogenesis?"
            ]
        },
        {
            "id": "task847-8e92402907a646bcbe32f341dd06b782",
            "input": "Biliary tract obstruction is a common clinical problem. In this study, we attempted to understand the change in intestinal glucose absorption after biliary tract obstruction.', 'Experimental models of murine biliary duct ligation and external biliary drainage were established. Murine intestinal mucosal glucose absorption was examined with Ussing chambers according to the increase in the short-circuit current in\\xa0vitro and blood glucose measurement after oral glucose in\\xa0vivo. The protein expression of the sodium-glucose cotransporter (SGLT1) and the facilitated glucose transporter, member 2 (GLUT2) was analyzed by Western blot and immunohistochemistry.', 'The results from Ussing chamber experiments showed that duodenal mucosal glucose absorption levels were significantly higher in biliary duct ligation and biliary drainage mice than those in normal control mice at 1 and 2\\xa0weeks after the operation. Gastrointestinal bile acid administration almost reversed the elevated duodenal mucosal glucose absorption to the normal level in biliary drainage mice. The results from the experiments in\\xa0vivo further confirmed that the glucose absorption increased in biliary duct ligation and biliary drainage mice. The protein expression levels of SGLT1 in the duodenal mucosae of both biliary duct ligation and biliary drainage mice were markedly higher than those in control mice, and the protein expression of GLUT2 was not significantly altered, compared with control mice.",
            "output": [
                "Does bile deficiency induce changes in intestinal glucose absorption in mice?"
            ]
        },
        {
            "id": "task847-919bb2777f934090bf91cd98e1fa3f6b",
            "input": "Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC.', 'All patients with UC diagnosed <17\\u2005years from 1988 to 2004, and followed during >2\\u2005years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-\u03b1) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models.', '158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5\\u2005years (Q1: 11.4-Q3: 16.1) have been identified and followed during a median of 11.4\\u2005years (8.2-15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1\\u2005year, 45% at 5\\u2005years and 52% at 10\\u2005years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1\\u2005year, 10% at 5\\u2005years, 13% at 10\\u2005years and 13% at 15\\u2005years. Risks for colonic extension, treatment with anti-TNF-\u03b1 and colectomy did not differ between the E1 group and the E2-E3-E4 group.",
            "output": [
                "Is ulcerative proctitis a frequent location of paediatric-onset UC and not a minor disease : a population-based study?"
            ]
        },
        {
            "id": "task847-8168a0c896d444e786be1360a09d290a",
            "input": "The advent of the Internet has driven a technological revolution that has changed our lives. As part of this phenomenon, social networks have attained a prominent role in health care. A variety of medical services is provided over the Internet, including home monitoring, interactive communications between the patient and service providers, and social support, among others. This study emphasizes some of the practical implications of Web-based health social networks for patients and for health care systems.', 'The objective of this study was to assess how participation in a social network among individuals with a chronic condition contributed to patient activation, based on the Patient Activation Measure (PAM).', 'A prospective, cross-sectional survey with a retrospective component was conducted. Data were collected from Camoni, a Hebrew-language Web-based social health network, participants in the diabetes mellitus, pain, hypertension, and depression/anxiety forums, during November 2012 to 2013. Experienced users (enrolled at least 6 months) and newly enrolled received similar versions of the same questionnaire including sociodemographics and PAM.', 'Among 686 participants, 154 of 337 experienced and 123 of 349 newly enrolled completed the questionnaire. Positive correlations (P<.05) were found between frequency and duration of site visits and patient activation, social relationships, and chronic disease knowledge. Men surfed longer than women (\u03c7\u00b23=10.104, P<.05). Experienced users with diabetes surfed more than those with other illnesses and had significantly higher PAM scores (mean, M=69.3, standard deviation, SD=19.1, PAM level 4; Z=-4.197, P<.001) than new users (M=62.8, SD=18.7, PAM level 3). Disease knowledge directly predicted PAM for all users (\u03b2=.26 and .21, respectively). Frequency and duration of social health network use were correlated with increased knowledge about a chronic disease. Experienced surfers had higher PAM than newly enrolled, suggesting that continued site use may contribute to increased activation.",
            "output": [
                "Is frequent Surfing on Social Health Networks Associated With Increased Knowledge and Patient Health Activation?"
            ]
        },
        {
            "id": "task847-9de0497cc268468dacb03ba4504492d6",
            "input": "Bleach is widely used for household cleaning. Although it is recognized that occupational use of bleach may have adverse respiratory health effects, it is unknown whether common domestic use of bleach may be a risk factor for asthma.', 'To assess whether the domestic use of bleach for home cleaning is associated with asthma and other respiratory outcomes.', 'Questionnaire-based information on respiratory symptoms and cleaning habits and data from skin prick-tests, bronchial responsiveness challenge and white blood cells were analyzed in 607 women participating in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). Bleach use was evaluated in 3 categories (<1\\xa0day/week; 1-3\\xa0days/week; 4-7\\xa0days/week \"frequent\").', 'Overall, 37% of the women reported using bleach weekly. Women using bleach frequently (11%) were more likely to have current asthma as compared to non-users (adjusted Odds-Ratio (aOR)\\xa0=\\xa01.7; 95% Confidence Interval (95%CI) 1.0-3.0). Among women with asthma, frequent use of bleach was significantly associated with higher blood neutrophil cell counts. Bleach use was significantly associated with non-allergic asthma (aOR 3.3; 95%CI 1.5-7.1), and more particularly with non-allergic adult-onset asthma (aOR 4.9; 95%CI 2.0-11.6). Consistently, among women without allergic sensitization, significant positive associations were found between use of bleach and bronchial hyperresponsiveness, asthma like-symptoms and chronic cough. No association was observed for allergic asthma.",
            "output": [
                "Are women using bleach for home cleaning at increased risk of non-allergic asthma?"
            ]
        },
        {
            "id": "task847-431b824842a844009aaaff3c34d01471",
            "input": "Treatment resistance and metastasis are the major causes of death among patients with colorectal cancer (CRC). Approximately 20% of surgically treated patients ultimately develop metastases during the follow-up period. Currently, the TNM system is the only available prognostic test. Therefore, the identification of new markers for CRC remains important. Thrombomodulin (TM), a glycoprotein, is involved in angiogenesis and has been linked to many malignant diseases. However, the function of TM in CRC remains unclear.', 'A total of 170 patients with CRC participated in this study. TM expression was analyzed via immunohistochemistry. Univariate (Kaplan-Meier) analysis was used to analyze patient outcomes, including overall survival (OS) and disease-free survival (DFS). TM expression was manipulated using shRNA or an overexpression system. Transwell migration assays, wound healing migration assays, and the xCELLigence biosensor system were used to detect cell proliferative and migratory capacities.', \"TM expression in the tumor tissues significantly and positively correlated with the DFS and OS of non-metastatic patients with CRC (ps = 0.036 and 0.0218, respectively). Suppression of TM expression increased the proliferation and migration of DLD-1 cells. TM overexpression reduced the cells' proliferative and migratory capacities. Cyclooxygenase (COX)-2 expression was up-regulated following TM silencing. Furthermore, the association between the migration of colon cancer cells and the levels of TM and epithelial-to-mesenchymal transition (EMT) markers (fibronectin, vimentin and ezrin) was confirmed in HT29 and DLD-1 cells.",
            "output": [
                "Does thrombomodulin influence the Survival of Patients with Non-Metastatic Colorectal Cancer through Epithelial-To-Mesenchymal Transition ( EMT )?"
            ]
        },
        {
            "id": "task847-f7cfb740cdde40ca9d425653592d1e34",
            "input": "To evaluate response to radiation and clinical outcome of uterine cervical cancer patients with tumor-related leukocytosis (TRL) at initial diagnosis and during definitive radiotherapy.', 'We retrospectively analyzed 2456 patients with stage IA-IVA uterine cervical cancer who received definitive radiotherapy with (37.4%) or without (62.6%) platinum-based chemotherapy between 1986 and 2012. TRL was defined as two or more occurrences of leukocytosis over 9000/\u03bcl at the time of diagnosis and during the course of treatment. Locoregional failure-free survival (LFFS) and overall survival (OS) were compared between patients with or without TRL.', 'The median age of all patients was 55 years, and the median follow-up time was 65.1 months. TRL was observed in 398 patients (16%) at initial diagnosis; TRL (+) patients were younger and had larger tumors, advanced stage, and more frequent lymph node metastases (all P < 0.05). TRL (+) patients showed a significantly lower rate of complete remission than TRL (-) patients (89.9% versus 96.3%, respectively, P = 0.042). Ten-year LFFS and OS for all patients were 84% and 78%, respectively. LFFS and OS were significantly lower in TRL (+) patients than TRL (-) patients (10-year LFFS: 69% versus 87% respectively, P < 0.001; 10-year OS: 63% versus 81% respectively P < 0.001). After propensity score matching, LFFS and OS rates in TRL (+) patients remained significantly lower than for TRL (-) patients; this significant difference was also observed on multivariate analysis. Twenty-six percent of patients with locoregional failure (n = 345) were TRL (+) and had significantly poorer median OS (6 versus 12 months, P = 0.001).",
            "output": [
                "Is tumor-related leukocytosis associated with poor radiation response and clinical outcome in uterine cervical cancer patients?"
            ]
        },
        {
            "id": "task847-cbb3aa96a1f0476983f16c0afa6288c7",
            "input": "Gene therapeutic strategies with suicide genes are currently investigated in clinical trials for brain tumors. Previously, we have shown that lentiviral vectors delivering the suicide gene HSV-Tk to experimental brain tumors promote a highly significant treatment effect and thus are promising vectors for clinical translation.', 'In the present study, we tested lentiviral vectors delivering the suicide gene HSV-Tk.007, a highly active mutant of HSV-Tk, to rat brains as a preclinical toxicity study. We injected 10(6) vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped functional lentiviral particles harboring the suicide gene HSV-Tk.007 into the brain of healthy, immunocompetent rats. During prodrug treatment with ganciclovir (GCV), we measured weight and assessed the behavior of the rats in an open field test. After 14\\u2009days of GCV treatment, we analyzed HSV-Tk.007 expression in different brain cell populations, as well as inflammatory responses and apoptosis.', 'During prodrug treatment with GCV, behavior experiments did not reveal differences between the treated rats and the control groups. Analysis of HSV-Tk expression in different brain cell populations showed that transduced normal brain cells survived GCV treatment. There were no statistically significant differences in the number of transduced cells between treatment and control groups. Furthermore, inflammatory responses and apoptosis of brain cells were not observed.",
            "output": [
                "Is lentiviral HSV-Tk.007-mediated suicide gene therapy toxic for normal brain cells?"
            ]
        },
        {
            "id": "task847-3e41b8b02c80475b954ec807e8aacbe2",
            "input": "Vascular calcification can predict cardiovascular (CV) morbidity and mortality in patients with end-stage renal disease. We evaluated the prevalence, association factors, and outcomes of chest X-ray-detected aortic arch calcification (AoAC) in patients undergoing peritoneal dialysis (PD).', 'We included 190 patients undergoing PD (mean age, 52.6\\xa0\u00b1\\xa014.3\\xa0years) for whom chest radiographs were available. AoAC revealed by chest X-ray was graded from 0 to 3 according to an AoAC score (AoACS). Multiple regression analyses were used to determine the factors associated with AoACS. After adjusting for age, sex, PD duration, diabetes mellitus, mean blood pressure, and history of CV disease, the association between AoAC grading and mortality were assessed using the Kaplan-Meier curve and Cox proportional hazard model.', 'Age (p\\xa0<\\xa00.001), PD duration (p\\xa0=\\xa00.004), history of CV disease (p\\xa0<\\xa00.001), and renal Kt/V (p\\xa0=\\xa00.031) were associated with AoACS. After a mean follow-up of 55.1\\xa0\u00b1\\xa032.1\\xa0months, patients with Grade 2 (p\\xa0=\\xa00.011) or Grade 3 (p\\xa0<\\xa00.001) AoAC had higher all-cause mortality than patients with Grade 0 AoAC. In addition, patients with Grades 2 and 3 AoAC had higher CV-related mortality than those with Grades 0 and 1 AoAC (p\\xa0=\\xa00.013). Grade 2 [hazard ratio (HR)\\xa0=\\xa02.736; 95% confidence interval (CI), 1.038-7.211; p\\xa0=\\xa00.042] and Grade 3 AoAC (HR\\xa0=\\xa03.289; 95% CI, 1.156-9.359; p\\xa0=\\xa00.026) remained associated with all-cause mortality after adjustment. Similarly, Grades 2 and 3 AoAC (HR\\xa0=\\xa036.05; 95% CI, 3.494-372; p\\xa0=\\xa00.026) significantly correlated with CV mortality after adjustment.",
            "output": [
                "Does severe aortic arch calcification predict mortality in patients undergoing peritoneal dialysis?"
            ]
        },
        {
            "id": "task847-7d7ef6799169412c933df63ce7976c36",
            "input": "Proliferative vitreoretinopathy (PVR) is a blinding disorder that develops after a retinal tear or detachment. Activation of the retinal pigmented epithelium (RPE) is implicated in PVR; however, the mechanisms leading to enhanced RPE proliferation, migration, and contraction remain largely unknown. This study utilized an in vitro model of PVR to investigate the role of acetylation in RPE activation and its contribution to the progression of this disease.', 'ARPE-19 cells, primary cultures of porcine RPE, and induced pluripotent stem cell-derived RPE (iPS-RPE) were utilized for cellular and molecular analyses. Cells treated with transforming growth factor beta 2 (TGF\u03b22; 10\\u2009ng/mL) alone or in the presence of the broad-spectrum histone deacetylase (HDAC) inhibitor, trichostatin A (TSA; 0.1\\u2009\u03bcM), were assessed for contraction and migration through collagen contraction and scratch assays, respectively. Western blotting and immunofluorescence analysis were performed to assess \u03b1-smooth muscle actin (\u03b1-SMA) and \u03b2-catenin expression after TGF\u03b22 treatment alone or in combination with TSA.', 'TGF\u03b22 significantly increased RPE cell contraction in collagen matrix and this effect was inhibited in the presence of TSA (0.1\\u2009\u03bcM). In agreement with these data, immunofluorescence analysis of TSA-treated iPS-RPE wounded monolayers revealed decreased \u03b1-SMA as compared with control. Scratch assays to assess wound healing revealed TSA inhibited TGF\u03b22-mediated iPS-RPE cell migration.",
            "output": [
                "Does trichostatin A inhibit Retinal Pigmented Epithelium Activation in an In Vitro Model of Proliferative Vitreoretinopathy?"
            ]
        },
        {
            "id": "task847-8cc8e375106644f8ae618204506147a1",
            "input": "Traumatic brain injury (TBI) is a complex process that increasing evidence has demonstrated that reactive oxygen species contribute to brain injury. Revesterol (RVT), which exhibits significant antioxidant properties, is neuroprotective against excitotoxicity, ischemia, and hypoxia. Our aim was to evaluate the neuroprotective effects of RVT on the hippocampus in a rat model of TBI.', \"Seven rats were divided into four. A moderate degree of head trauma was induced using Feeney's falling weight technique. Group1 (control) underwent no intervention. Head trauma was induced in the Group 2 (trauma) and, no drug was administered. Head trauma was induced in the Group 3 rats and low-dose RVT (50 mg/kg per day) was injected and in the fourth group, high-dose RVT (100 mg/kg per day) was used. Brain tissues were extracted immediately after perfusion without damaging the tissues. Histopathological and biochemistry parameters were studied.\", 'Brain tissue malondialdehyde (MDA) levels in the trauma group were significantly higher than those in the control, low-dose RVT-treated, and high-dose-RVT-treated groups. The superoxide dismutase (SOD) levels in the control group were significantly higher than those in the trauma, low-dose RVT-treated, and high-dose RVT-treated groups. Glutathione peroxidase (GSH-Px) levels in the control group were significantly higher than those in the trauma and low-dose RVT-treated groups. The level of oxidative DNA damage (8-OHdG/106 dG) in the trauma group was higher than that in the control group, low-dose RVT-treated, and high-dose RVT-treated groups.",
            "output": [
                "Does rESVERATROL TREATMENT prevent HIPPOCAMAL NEURODEGENERATION IN A RODENT MODEL OF TRAUMATIC BRAIN INJURY?"
            ]
        },
        {
            "id": "task847-919d9a1a6c504710b49fa4df4ded8568",
            "input": "Recessive mutations in GHRHR are associated with severe isolated growth hormone deficiency (IGHD), with a final height in untreated patients of 130 cm \u00b1 10 cm (-7.2 \u00b1 1.6 SDS; males) and 114 \u00b1 0.7 cm (-8.3 \u00b1 0.1 SDS; females).', 'We hypothesized that a consanguineous Pakistani family with IGHD in three siblings (two males, one female) would have mutations in GH1 or GHRHR.', 'Two novel homozygous missense variants [c.11G>A (p.R4Q), c.236C>T (p.P79L)] at conserved residues were identified in all three siblings. Both were absent from control databases, aside from pR4Q appearing once in heterozygous form in the Exome Aggregation Consortium Browser. The brothers were diagnosed with GH deficiency at 9.8 and 6.0 years (height SDS: -2.24 and -1.23, respectively), with a peak GH of 2.9 \u03bcg/liter with low IGF-1/IGF binding protein 3. Their sister presented at 16 years with classic GH deficiency (peak GH <0.1 \u03bcg/liter, IGF-1 <3.3 mmol/liter) and attained an untreated near-adult height of 144 cm (-3.0 SDS); the tallest untreated patient with GHRHR mutations reported. An unrelated Pakistani female IGHD patient was also compound homozygous. All patients had a small anterior pituitary on magnetic resonance imaging. Functional analysis revealed a 50% reduction in maximal cAMP response to stimulation with GHRH by the p.R4Q/p.P79L double mutant receptor, with a 100-fold increase in EC50.",
            "output": [
                "Does partial Loss of Function of the GHRH Receptor lead to Mild Growth Hormone Deficiency?"
            ]
        },
        {
            "id": "task847-9a9922bd302c40afbf93882298f452a5",
            "input": "Morphine and other opioids are routinely used systemically and as wound infusions in the postoperative period. Their effect on wound and fracture healing remains unclear.', 'The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of morphine on human fibroblasts.', 'Laboratory in-vitro study.', 'Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich.', 'Monolayers of human fibroblasts.', 'Exposure of human fibroblast monolayers to several concentrations of morphine, for different periods of time, with and without an artificially induced inflammatory process.', 'Cell count, cell viability, cell proliferation and apoptosis.', 'A concentration, time and exposure-dependent cytotoxic effect of morphine-mediated apoptosis was observed. Simulated inflammatory conditions seemed to lessen toxic effects.",
            "output": [
                "Are clinical concentrations of morphine cytotoxic on proliferating human fibroblasts in vitro?"
            ]
        },
        {
            "id": "task847-58be28639f8e4b209814eec735dd0d8b",
            "input": "We noted a bimodal relationship between mortality and shock index (SI), the ratio of heart rate to systolic blood pressure.', 'To determine if extremes of SI can predict mortality in trauma patients.', 'Retrospective evaluation of adult trauma patients at a tertiary care center from 2000 to 2012 in the United States.', 'We examined the SI in trauma patients and determined the adjusted mortality for patients with and without head injuries.', 'Descriptive statistics and multivariable logistic regression.', 'SI values demonstrated a U-shaped relationship with mortality. Compared with patients with a SI between 0.5 and 0.7, patients with a SI of <0.3 had an odds ratio for death of 2.2 (95% confidence interval [CI] 21.2-4.1) after adjustment for age, Glasgow Coma score, and injury severity score while patients with SI >1.3 had an odds ratio of death of 3.1. (95% CI 1.6-5.9). Elevated SI is associated with increased mortality in patients with isolated torso injuries, and is associated with death at both low and high values in patients with head injury.",
            "output": [
                "Does extremes of shock index predict death in trauma patients?"
            ]
        },
        {
            "id": "task847-2c41d5db616f44838502889c5723d379",
            "input": "Human skeletal muscles express three major myosin heavy chain (MyHC) isoforms: MyHCIIx (MYH1) in fast type 2B muscle fibers, MyHCIIa (MYH2) in fast type 2A fibers and MyHCI/\u03b2-cardiac MyHC (MYH7) in slow type I skeletal fibers and cardiac ventricles. In line with its expression pattern, MYH7 mutations have been reported in association with hypertrophic or dilated cardiomyopathy, skeletal myopathies or a combination of both. We analyzed the clinical and molecular phenotype of two unrelated families of Jewish Moroccan ancestry that presented with apparently autosomal dominant inheritance of progressive Laing-like distal myopathy with non-specific myopathic changes, but uncommon marked contractures and wasting of the neck extensors.', 'Clinical phenotyping, whole exome sequencing and restriction analysis, generation of mutants followed by cell culture transfection and imaging.', 'Using whole exome sequencing we identified in both families two novel heterozygous proline substitutions located in exon 31 of MYH7 within its rod domain: c.4309G>C (p.Ala1437Pro) and c.4301G>C (p.Arg1434Pro). Here we show that the phenotype caused by these mutations includes marked cervical muscle contracture, and report that the severity of the phenotype varies significantly, to the extent of non-penetrance in one of the families. Finally, we provide evidence that both proline substitutions impair myosin self-assembly in non-muscle cells transfected with \u03b2-myosin constructs carrying the mutations, but do not prevent incorporation of the mutant molecules into the sarcomere.",
            "output": [
                "Do two novel MYH7 proline substitutions cause Laing Distal Myopathy-like phenotypes with variable expressivity and neck extensor contracture?"
            ]
        },
        {
            "id": "task847-e2bc30b8546f42f3a5269ea7af434908",
            "input": "Multi-atlas fusion is a promising approach for computer-assisted segmentation of anatomic structures. The purpose of this study was to evaluate the accuracy and time efficiency of multi-atlas segmentation for estimating spleen volumes on clinically acquired computed tomography (CT) scans.', 'Under an institutional review board approval, we obtained 294 de-identified (Health Insurance Portability and Accountability Act-compliant) abdominal CT scans on 78 subjects from a recent clinical trial. We compared five pipelines for obtaining splenic volumes: Pipeline 1 - manual segmentation of all scans, Pipeline 2 - automated segmentation of all scans, Pipeline 3 - automated segmentation of all scans with manual segmentation for outliers on a rudimentary visual quality check, and Pipelines 4 and 5 - volumes derived from a unidimensional measurement of craniocaudal spleen length and three-dimensional splenic index measurements, respectively. Using Pipeline 1 results as ground truth, the accuracies of Pipelines 2-5 (Dice similarity coefficient, Pearson correlation, R-squared, and percent and absolute deviation of volume from ground truth) were compared for point estimates of splenic volume and for change in splenic volume over time. Time cost was also compared for Pipelines 1-5.', 'Pipeline 3 was dominant in terms of both accuracy and time cost. With a Pearson correlation coefficient of 0.99, average absolute volume deviation of 23.7\\u2009cm(3), and time cost of 1 minute per scan, Pipeline 3 yielded the best results. The second-best approach was Pipeline 5, with a Pearson correlation coefficient of 0.98, absolute deviation of 46.92\\u2009cm(3), and time cost of 1 minute 30 seconds per scan. Manual segmentation (Pipeline 1) required 11 minutes per scan.",
            "output": [
                "Does improving Spleen Volume Estimation Via Computer-assisted Segmentation on Clinically Acquired CT scan?"
            ]
        },
        {
            "id": "task847-ed8d53e596b849aeb1c60056cba09fcf",
            "input": "To systematically review methodological articles which focus on nonpublication of studies and to describe methods of detecting and/or quantifying and/or adjusting for dissemination in meta-analyses. To evaluate whether the methods have been applied to an empirical data set for which one can be reasonably confident that all studies conducted have been included.', 'We systematically searched Medline, the Cochrane Library, and Web of Science, for methodological articles that describe at least one method of detecting and/or quantifying and/or adjusting for dissemination bias in meta-analyses.', 'The literature search retrieved 2,224 records, of which we finally included 150 full-text articles. A great variety of methods to detect, quantify, or adjust for dissemination bias were described. Methods included graphical methods mainly based on funnel plot approaches, statistical methods, such as regression tests, selection models, sensitivity analyses, and a great number of more recent statistical approaches. Only few methods have been validated in empirical evaluations using unpublished studies obtained from regulators (Food and Drug Administration, European Medicines Agency).",
            "output": [
                "Are methods for detecting , quantifying , and adjusting for dissemination bias in meta-analysis described?"
            ]
        },
        {
            "id": "task847-78336db2971a4762a39dd5d141489bda",
            "input": "Metabolic adverse effects of atypical antipsychotics (AAP) contribute significantly to increased risk of cardiovascular morbidity and mortality in patients suffering from schizophrenia. Extensive preclinical research has addressed this issue over the past years, though mechanisms underlying these adverse effects of AAP are still not understood completely. Recently, attention is drawn towards the role of adipose tissue metabolism and neurohormonal regulations.', 'The aim of this study was to evaluate the time-dependent effects of olanzapine depot administration at clinically relevant dosing on the regulation of energy homeostasis, glucose and lipid metabolism, gastrointestinal and adipose tissue-derived hormones involved in energy balance regulations in female Sprague-Dawley rats. The study lasted 8 weeks and the markers were assayed at day 8, 15, 29, 43 and 57.', 'The results indicate that in the absence of hyperphagia, olanzapine chronic exposure induced weight gain from the beginning of the study. In the later time-point, increased adiposity was also observed. In the initial phase of the study, lipid profile was altered by an early increase in triglyceride level and highly elevated leptin level was observed. Clear bi-phasic time-dependent effect of olanzapine on leptin serum concentration was demonstrated. Olanzapine treatment did not lead to changes in serum levels of ghrelin, FGF-21 and pro-inflammatory markers IL-1a, IL-6 and TNF-\u03b1 at any time-point of the study.",
            "output": [
                "Does olanzapine-depot administration induce time-dependent changes in adipose tissue endocrine function in rats?"
            ]
        },
        {
            "id": "task847-1b5125e2de74478a97f095d791966be6",
            "input": "To determine the relationship between geophagy (mouthing of dirt, sand, clay, or mud) and growth faltering in young children.', 'We examined linear growth as height and weight standardized by age and sex, and weight standardized by height, in a cohort of children aged 6-36 months in rural Mirzapur, Bangladesh. We determined geophagy behavior at baseline through caregiver report. Anthropometric measurements were assessed at baseline and at a 1-year follow-up.', 'We found that among children not stunted at baseline, those with caregiver-reported geophagy at baseline grew less over 1 year compared with their peers, with a difference in the change of standardized height for age and sex of -0.31 (95% CI, -0.61 to -0.01).",
            "output": [
                "Does geophagy be Associated with Growth Faltering in Children in Rural Bangladesh?"
            ]
        },
        {
            "id": "task847-fb8e034f94344ab6b428645854f6c0f1",
            "input": "To determine if children with benign joint hypermobility (BJH) syndrome and chronic functional pain disorders have more autonomic dysfunction.', 'Retrospective chart review study of pediatric patients seen in the pediatric neurogastroenterology and autonomic clinic who underwent autonomic testing and had either a Beighton score of \u22656 and met Brighton criteria for BJH (with BJH) or a score of \u22642 (no BJH).', 'Twenty-one female subjects (10 without BJH) met inclusion criteria; 64% of BJH had diagnosis confirmed by genetics consultation. We evaluated for postural tachycardia syndrome, syncope, orthostatic intolerance, and orthostatic hypotension. None of these diagnoses, as well as baseline heart rate, peak heart rate in first 10\\u2009minutes of head up tilt (P\\u2009=\\u2009.35 and P\\u2009=\\u2009.61, respectively), and sudomotor index (suggestive of autonomic neuropathy) (P\\u2009=\\u2009.58), showed differences between the groups. Age of onset of symptoms was also similar (P\\u2009=\\u2009.61) (BJH vs without BJH: median [range]:15.6 years [12.9-17.5] vs 15.4 years [11.1-18.2]). There was no difference between groups in complaints of migraine, chronic nausea, chronic fatigue, lightheadedness, dizziness, fainting >3 times/lifetime, delayed onset of sleep, irritable bowel syndrome, dyspepsia, abdominal migraine, functional abdominal pain, constipation, or fibromyalgia.",
            "output": [
                "Does benign Joint Hypermobility Minimally impact Autonomic Abnormalities in Pediatric Subjects with Chronic Functional Pain Disorders?"
            ]
        },
        {
            "id": "task847-3ae013be9b564b219bd2425ef51ac374",
            "input": "The symptoms of sleep apnea, such as sleep fragmentation and oxygen desaturation, might be risk factors for subsequent mood disorder (MD), but associations between sleep apnea and MD remain unclear. This nationwide population-based study thus aimed to identify the risk of MD in patients with vs. without sleep apnea.', 'This cohort study used data from the National Health Insurance database. In total, 5415 patients diagnosed with sleep apnea between 2000 and 2010 were evaluated, and 27,075 matched non-sleep apnea enrollees were included as a comparison cohort. All subjects were followed until 2011. The Cox proportional hazard ratio (HR) was used to investigate the relationship between MD and sleep apnea while controlling covariates and comorbidities of sleep apnea.', 'Of 5415, 154 patients with sleep apnea (2.84\\xa0%) were diagnosed with MD during the follow-up period in comparison with 306 of 27,075 individuals (1.13\\xa0%) without antecedent sleep apnea. After adjusting for the selected factors and comorbidities, we found that patients with sleep apnea were from 1.82- to 2.07-fold greater risk of MD than the comparisons. Of the three subcategories of MD (major depressive disorder, bipolar disorder, and unspecified MD), sleep apnea had the highest predisposing risk with respect to major depressive disorder (adjusted HR from 1.82 to 2.07) and bipolar disorder (adjusted HR from 2.15 to 3.24).",
            "output": [
                "Is sleep apnea associated with an increased risk of mood disorders : a population-based cohort study?"
            ]
        },
        {
            "id": "task847-b239b054f9e6458c9634afa1f4743351",
            "input": "Carriage of the HLA-Cw*0602 allele is associated with a particular set of clinical features and treatment responses in psoriasis. Tonsillectomy can improve psoriasis.', 'We sought to evaluate whether HLA-Cw*0602 predicts a favorable outcome after tonsillectomy of patients with psoriasis.', 'This prospective case series followed up 28 tonsillectomized patients with plaque psoriasis for 24\\xa0months. The Psoriasis Area and Severity Index, Psoriasis Disability Index, and Psoriasis Life Stress Inventory were used for assessment. Tonsils were swabbed for bacteria and patients genotyped for HLA-Cw*0602.', 'After tonsillectomy, HLA-Cw*0602 homozygotes showed significantly more improvement, compared with heterozygous and HLA-Cw*0602-negative patients. Thus, Psoriasis Area and Severity Index score was reduced by 82% in the homozygous patients compared with 42% and 31%, respectively (P\\xa0<\\xa0.001), Psoriasis Disability Index score improved by 87% compared with 38% and 41%, respectively (P\\xa0<\\xa0.001), and Psoriasis Life Stress Inventory score was 82% reduced compared with 60% and 54%, respectively (P\\xa0<\\xa0.001). The homozygotes more often had psoriasis onset associated with a throat infection (P\\xa0=\\xa0.007) and an increased frequency of streptococcal throat infections per lifetime (P\\xa0=\\xa0.038).",
            "output": [
                "Is hLA-Cw6 homozygosity in plaque psoriasis associated with streptococcal throat infections and pronounced improvement after tonsillectomy : A prospective case series?"
            ]
        },
        {
            "id": "task847-f4168e57667345419813dd8fec89dada",
            "input": "A number of studies have suggested that depressed mood is one of the most important predictors of quality of life (QoL) in patients with epilepsy. However, the QoL measure used in previous studies was limited to the Quality of Life in Epilepsy (QOLIE) scales. It could be questioned whether correlation of QOLIE with measures of depression is influenced by the properties of the instruments used rather than being a valid effect. By using visual analogue scales, the current study aimed to clarify whether depression and QoL are truly correlated in patients with epilepsy.', \"Data from a sample of 261 outpatients with epilepsy attending the Epilepsy Clinics of the Atkinson Morley Outpatient Department, St George's Hospital in London, were analyzed. Patients were screened using the European Quality-of-Life scale (EQ-5D-3L) which includes an overall visual analogue score (EQ-VAS), the Emotional Thermometer (ET7), the Beck Depression inventory-II (BDI-II), the Hospital Anxiety and Depression scale (HADS), and the Major Depression inventory (MDI).\", 'Depression was found to significantly correlate with EQ-VAS score with r coefficient ranging from 0.42 to 0.51 and r(2) coefficients ranging between 0.18 and 0.26. In addition, we identified patients who were depressed according to DSM-IV criteria (MD) and those with atypical forms of depression (AD). The EQ-5D-3L scores in these subjects compared with those without depression (ND) showed a different impact of AD and MD on QoL.",
            "output": [
                "Does depression correlate with quality of life in people with epilepsy independent of the measures used?"
            ]
        },
        {
            "id": "task847-90a9d132d71f4b6492eccc00cafcec8a",
            "input": "Centrifuge training, while an integral component in pilot training, is not without risks. To date there has never been a reported case of isolated transverse process fractures associated with centrifuge training.', 'A 32-yr-old Flight Surgeon underwent centrifuge training as part of an educational course. She had increasing back pain after exposure to the centrifuge. Follow-up studies showed left L2 and bilateral L3 transverse process fractures. No other contributory causes could be identified except for mild vitamin D deficiency.",
            "output": [
                "Do a Report of Transverse Process Fractures Secondary to the Centrifuge in a Healthy Aviator?"
            ]
        },
        {
            "id": "task847-07faec4b45c5474d90a57b42564f48f2",
            "input": "Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets.', 'Direct interactions of uPAR with interactors were demonstrated by immunoprecipitations and proximity ligation assays. For stable knockdowns of target proteins, lentiviral vectors were used and the effects were analysed by immunoblottings and using in vitro cell viability, migration and invasion assays. Immunohistochemical and statistical analyses of biomarkers and clinical parameters were conducted in a TNBC cohort (n\\u2009=\\u2009174).', 'Direct tumour-promoting interactions of uPAR with uPA and the insulin-like growth factor receptor 1 (IGF1R) were shown in TNBC cells and these interactions were significantly reduced (p\\u2009=\\u20090.001) when uPAR was downregulated. The combined knockdown of uPAR and uPA or IGF1R additively and significantly reduced cell viability, migration and invasion of the model cell lines. In TNBC tissue, the complexes formed by uPAR with uPA or with IGF1R significantly correlated with the histological grade (p\\u2009=\\u20090.0019) as well as with cathepsin B and D (p\\u2009\u2264\\u20090.0001) that are implicated in cell invasion and metastasis.",
            "output": [
                "Does uPAR enhance malignant potential of triple-negative breast cancer by directly interacting with uPA and IGF1R?"
            ]
        },
        {
            "id": "task847-de0f16c0a98f408a92cfc279794f2600",
            "input": "Biohythane is a new and high-value transportation fuel present as a mixture of biomethane and biohydrogen. It has been produced from different organic matters using anaerobic digestion. Bioenergy can be recovered from waste activated sludge through methane production during anaerobic digestion, but energy yield is often insufficient to sludge disposal. Microbial electrolysis cell (MEC) is also a promising approach for bioenergy recovery and waste sludge disposal as higher energy efficiency and biogas production. The systematic understanding of microbial interactions and biohythane production in MEC is still limited. Here, we report biohythane production from waste sludge in biocathode microbial electrolysis cells and reveal syntrophic interactions in microbial communities based on high-throughput sequencing and quantitative PCR targeting 16S rRNA gene.', 'The alkali-pretreated sludge fed MECs (AS-MEC) showed the highest biohythane production rate of 0.148\\xa0L\u00b7L(-1)-reactor\u00b7day(-1), which is 40 and 80\\xa0% higher than raw sludge fed MECs (RS-MEC) and anaerobic digestion (open circuit MEC, RS-OCMEC). Current density, metabolite profiles, and hydrogen-methane ratio results all confirm that alkali-pretreatment and microbial electrolysis greatly enhanced sludge hydrolysis and biohythane production. Illumina Miseq sequencing of 16S rRNA gene amplicons indicates that anode biofilm was dominated by exoelectrogenic Geobacter, fermentative bacteria and hydrogen-producing bacteria in the AS-MEC. The cathode biofilm was dominated by fermentative Clostridium. The dominant archaeal populations on the cathodes of AS-MEC and RS-MEC were affiliated with hydrogenotrophic Methanobacterium (98\\xa0%, relative abundance) and Methanocorpusculum (77\\xa0%), respectively. Multiple pathways of gas production were observed in the same MEC reactor, including fermentative and electrolytic H2 production, as well as hydrogenotrophic\\xa0methanogenesis and electromethanogenesis. Real-time quantitative PCR analyses showed that higher amount of methanogens were enriched in AS-MEC than that in RS-MEC and RS-OCMEC, suggesting that alkali-pretreated sludge and MEC facilitated hydrogenotrophic methanogen enrichment.",
            "output": [
                "Do multiple syntrophic interactions drive biohythane production from waste sludge in microbial electrolysis cells?"
            ]
        },
        {
            "id": "task847-dcd61ad3f1a449f08dd10120b965cd63",
            "input": "To investigate the presence of rmpA and wcaG virulence genes and Class 1, 2, and 3 integrons, and to evaluate a relationship between antibiotic resistance and virulence in Klebsiella pneumoniae METHODS: We collected a total of 200 K. pneumoniae isolates from hospitals in Tehran, Iran. Antibiotic susceptibility was determined using the disk diffusion method. The extended-spectrum \u03b2-lactamase (ESBL) producers were detected using the combination disk method. We detected the rmpA and wcaG genes and class 1, 2, and 3 integrons via polymerase chain reaction (PCR). The \u03c7', 'Of 200 isolates, 115 (57.5%) were ESBL producers; 74.0% carried the class 1 integron, and 1.0% carried the class 2 integron. The gene rmpA was detected in 7% of isolates and the gene wcaG in 23.5% of isolates. Integron-positive isolates showed a higher prevalence of wcaG compared with to integron-negative isolates (P\\u2009<.05).",
            "output": [
                "Does association Between Presence of Virulence Genes and Antibiotic Resistance in Clinical Klebsiella Pneumoniae isolate?"
            ]
        },
        {
            "id": "task847-66af2ebe4b4240ea9d17bfed4bf05df0",
            "input": "Antenatal vitamin D3 (vitD3) supplementation significantly increases maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the effect of an improvement in maternal-fetal vitamin D status on the neonatal immune response is unclear.', 'To assess the effect of prenatal vitD3 supplementation on cord blood T cell function, healthy pregnant Bangladeshi women (n\\u2009=\\u2009160) were randomized to receive either oral 35,000\\xa0IU/week vitD3 or placebo from 26 to 29\\xa0weeks of gestation to delivery. In a subset of participants (n\\u2009=\\u200980), cord blood mononuclear cells (CBMC) were cultured, non-adherent lymphocytes were isolated to assess T cell cytokine responses to phytohemagglutinin (PHA) and anti-CD3/anti-CD28 (iCD3/iCD28), measured by multiplex assay. In 12 participants, lymphocyte gene expression profiles were analyzed by PCR array.', 'In supplemented group, increased concentrations of IL-10 (P\\u2009<\\u20090.000) and TNF-\u03b1 (P\\u2009=\\u20090.05) with iCD3/iCD28 stimulation and IFN-\u03b3 (p\\u2009=\\u20090.05) with PHA stimulation were obtained compared to placebo group. No differences in the gene expression profile were noted between the two groups. However, PHA stimulation significantly induced the expression of genes encoding Th1 and Th2 cytokines and down-regulated a number of genes involved in T-cell development, proliferation and differentiation of B cells, signal transduction pathway, transcriptional regulation and pattern recognition receptors (PRRs) in the vitamin D group (vitD group).",
            "output": [
                "Does prenatal high-dose vitamin D3 supplementation have balanced effects on cord blood Th1 and Th2 responses?"
            ]
        },
        {
            "id": "task847-009246b2463948b8957d212d07df200f",
            "input": "New generation synthetic surfactants represent a promising alternative in the treatment of respiratory distress syndrome in preterm infants. CHF5633, a new generation reconstituted agent, has demonstrated biophysical effectiveness in vitro and in vivo. In accordance to several well-known surfactant preparations, we recently demonstrated anti-inflammatory effects on LPS-induced cytokine responses in human adult monocytes. The present study addressed pro- and anti-inflammatory effects of CHF5633 in human cord blood monocytes.', 'Purified neonatal CD14(+) cells, either native or simultaneously stimulated with E. coli LPS, were exposed to CHF5633. TNF-\u03b1, IL-1\u03b2, IL-8 and IL-10 as well as TLR2 and TLR4 expression were analyzed by means of real-time quantitative PCR and flow cytometry.', 'CHF5633 did not induce pro-inflammation in native human neonatal monocytes and did not aggravate LPS-induced cytokine responses. Exposure to CHF5633 led to a significant decrease in LPS-induced intracellular TNF-\u03b1 protein expression, and significantly suppressed LPS-induced mRNA and intracellular protein expression of IL-1\u03b2. CHF5633 incubation did not affect cell viability, indicating that the suppressive activity was not due to toxic effects on neonatal monocytes. LPS-induced IL-8, IL-10, TLR2 and TLR4 expression were unaffected.",
            "output": [
                "Does the new generation synthetic reconstituted surfactant CHF5633 suppress LPS-induced cytokine responses in human neonatal monocytes?"
            ]
        },
        {
            "id": "task847-5ba421f6836f426fb114cffdb9420981",
            "input": "MicroRNA-361-5p (miR-361-5p) has been reported to be tumor suppressor in colorectal, gastric and prostate cancer, but as an oncogene in cervical cancer. No previous research has focused on the expression of miR-361-5p and its exact prognostic role in breast cancer (BC).', 'In this study, a tissue microarray (TMA)-based miRNA detection in situ hybridization (ISH) with LNA probe was used to detect miR-361-5p expression in 375 BC tissue. The expression level of miR-361-5p in BC and its potential prognostic value was investigated.', 'Positive miR-361-5p staining was observed in 78.7% (N=295; 78.7% positive, 21.3% negative) in the 375 cases. The clinical outcome of patients with positive miR-361-5p expression [median disease-free survival (DFS) time 95.52 months] was significantly better than that of patients (median DFS time 82.33 months) with negative miR-361-5p expression (P=0.002). Moreover, the prognostic value of miR-361-5p was most significant among patients with triple-negative breast cancer (TNBC) for DFS (P=0.004).",
            "output": [
                "Does positive expression of miR-361-5p indicate better prognosis for breast cancer patients?"
            ]
        },
        {
            "id": "task847-25248ab97c9a44c68b654049c7114716",
            "input": "The aims of this study were to investigate the potential of \u03b2-catenin as a biomarker for predicting cancer-specific survival, and to find a reproducible mode of evaluation of immunohistochemistry.', '\u03b2-Catenin expression was analysed by immunohistochemistry in a cohort of 488 patients with conventional renal cell carcinoma (RCC) operated on between 2000 and 2010. The association between \u03b2-catenin expression and cancer-specific survival was assessed with univariate and multivariate Cox regression models in relation to conventional clinical pathological prognostic factors, and by Kaplan-Meier survival analysis with the log rank test. The univariate Cox regression model revealed an association of cytoplasmic \u03b2-catenin positivity and pathological variables with cancer-specific death. The multivariate Cox regression model analysis of tumours without metastatic disease at the first presentation identified the T-classification (P < 0.001) and cytoplasmic \u03b2-catenin positivity as risk factors for postoperative tumour progression. Specifically, cytoplasmic \u03b2-catenin expression was an independent factor indicating an unfavourable prognosis, with a four-fold higher risk of cancer-specific death (relative risk 4.017; 95% confidence interval 2.489-6.482; P < 0.001). The median survival time for patients with tumours showing cytoplasmic accumulation of \u03b2-catenin was 48 months, whereas the overall survival time was 166 months.",
            "output": [
                "Is cytoplasmic expression of \u03b2-catenin an independent predictor of progression of conventional renal cell carcinoma : a simple immunostaining score?"
            ]
        },
        {
            "id": "task847-1ce517a1ce0a405cbdde35bac3bb2589",
            "input": "Galectin-9 (Gal-9) is a \u03b2-galactoside-binding lectin that interacts with sugar moieties on glycoproteins and glycolipids of cells and pathogens. Gal-9 is known as an immune modulator that induces cell death via interaction with T cell immunoglobulin and mucin domain-3 (Tim3), a co-inhibitory receptor, and it inhibits production of several pro-inflammatory cytokines (TNF, IL-6 and IL-1\u03b1) and enhances production of IL-10. To understand the immune pathology of malaria, the Gal-9 in plasma was measured.', 'Plasma samples and clinical parameters were obtained from 50 acute malaria cases (nine severe and 41 uncomplicated cases) from Thailand at three time points: day 0, day 7 and day 28. Gal-9 levels were determined by ELISA. A total of 38 species of cytokines and chemokines were measured using a BioPlex assay.', 'Gal-9 levels were higher at day 0 compared to day 7 and day 28 (P\\xa0<\\xa00.0001). Gal-9 levels were also higher in severe malaria (SM) cases compared to uncomplicated (UM) cases at day 0 and day 7 (923 vs 617\\xa0pg/mL; P\\xa0=\\xa00.03, and 659 vs 348\\xa0pg/mL; P\\xa0=\\xa00.02 respectively). Median Gal-9 levels were higher in patients with blood urea nitrogen to creatinine ratio (BUN/creatinine)\\xa0\u226520 (mg/dL) than in patients with BUN/creatinine\\xa0<20 (mg/dL) at day 0 (817.3 vs 576.2\\xa0pg/mL, P\\xa0=\\xa00.007). Gal-9 was inversely significantly correlated with chloride levels in both SM and UM cases (r s\\xa0=\\xa0-0.73 and r s\\xa0=\\xa0-0.46, respectively). In both UM and SM cases, Gal-9 was significantly associated with pro- and anti-inflammatory cytokines and chemokines such as TNF, IL-6, IFN-\u03b12, IFN-\u03b3, IL-1Ra and IL-10. These correlations were observed at day 0 but disappeared at day 28.",
            "output": [
                "Do plasma levels of Galectin-9 reflect disease severity in malaria infection?"
            ]
        },
        {
            "id": "task847-47a4f09e5320493698df475578990c16",
            "input": "Previously, we found that application of pulsed radiofrequency to a peripheral nerve injury induces changes in key genes regulating nociception concurrent with alleviation of paw sensitivity in an animal model. In the current study, we evaluated such genes after applying spinal cord stimulation (SCS) therapy.', 'Male Sprague-Dawley rats (n = 6 per group) were randomized into test and control groups. The spared nerve injury model was used to simulate a neuropathic pain state. A 4-contact microelectrode was implanted at the L1 vertebral level and SCS was applied continuously for 72 hours. Mechanical hyperalgesia was tested. Spinal cord tissues were collected and analyzed using real-time polymerase chain reaction to quantify levels of IL1\u03b2, GABAbr1, subP, Na/K ATPase, cFos, 5HT3ra, TNF\u03b1, Gal, VIP, NpY, IL6, GFAP, ITGAM, and BDNF.', 'Paw withdrawal thresholds significantly decreased in spared nerve injury animals and stimulation attenuated sensitivity within 24 hours (P = 0.049), remaining significant through 72 hours (P = 0.003). Nerve injury caused up-regulation of TNF\u03b1, GFAP, ITGAM, and cFOS as well as down-regulation of Na/K ATPase. Spinal cord stimulation therapy modulated the expression of 5HT3ra, cFOS, and GABAbr1. Strong inverse relationships in gene expression relative to the amount of applied current were observed for GABAbr1 (R = -0.65) and Na/K ATPase (R = -0.58), and a positive linear correlations between 5HT3r (R = 0.80) and VIP (R = 0.50) were observed.",
            "output": [
                "Does spinal Cord Stimulation modulate Gene Expression in the Spinal Cord of an Animal Model of Peripheral Nerve Injury?"
            ]
        },
        {
            "id": "task847-386c41c895804dc68b31d646703fe4d7",
            "input": "While aberrant activation of the chromatin-remodeling SWI/SNF complexes has been associated with cancer development and progression, the role of each subunit in tumor cells is poorly defined. This study is aimed to characterize the role of SMARCE1/BAF57 in regulating metastasis of breast cancer cells.', 'Genetic approaches and chemical inhibitors were used to manipulate the activities of SMARCE1 and its downstream targets in multiple breast cancer cell lines. Xenograft mouse models were used to analyze the role of SMARCE1 in lung metastasis in vivo. Nonadherent culture conditions were used to elucidate the role of SMARCE1 in regulating anoikis. Chromatin immunoprecipitation (ChIP), immunoprecipitation, and immunoblotting assays were designed to dissect the mechanism of action of SMARCE1. Public databases were used to investigate the relationship between SMARCE1 deregulation and breast cancer prognosis.', 'SMARCE1 knockdown reduced lung metastasis of breast cancer cells and sensitized tumor cells to anoikis. In response to loss of attachment, SMARCE1 interacted with and potentiated transcriptional activity of HIF1A, resulting in rapid PTK2 activation. Both HIF1A and PTK2 were indispensable for SMARCE1-mediated protection against anoikis by promoting activation of ERK and AKT pathways while suppressing the expression of pro-apoptotic BIM protein. Expression data analysis of a large cohort of human breast tumors revealed that high expression of SMARCE1 or PTK2 is associated with poor prognosis and tumor relapse, and PTK2 expression is positively correlated with SMARCE1 expression in basal-like and luminal B subtypes of breast tumors.",
            "output": [
                "Does sMARCE1 regulate metastatic potential of breast cancer cells through the HIF1A/PTK2 pathway?"
            ]
        },
        {
            "id": "task847-a6521f3cc27a430ab1458cf9867129be",
            "input": "There is a scarcity of information on the effect of white matter degeneration in patients with spinocerebellar ataxia type 7. Therefore, we investigated the WM integrity in a large group of patients with spinocerebellar ataxia type 7 by using Tract-Based Spatial Statistics.', \"Thirty-three patients with a molecular diagnosis of spinocerebellar ataxia type 7 and their age- and sex-matched healthy controls participated in this study. The patients' ataxia severity was evaluated with the Scale for the Assessment and Rating of Ataxia. Voxelwise analyses of diffusion metrics, including fractional anisotropy and mean diffusivity, were performed with Tract-Based Spatial Statistics. The correlation between WM abnormalities and ataxia severity was then calculated.\", 'Tract-Based Spatial Statistics analysis revealed WM abnormalities in the cerebellum and the cerebellar peduncles, as well as in other major cortical and subcortical pathways. Further analysis between the Scale for the Assessment and Rating of Ataxia score and WM mean diffusivity showed significant associations only in key areas related to motor control and visuospatial processing, including the cerebellar WM, the middle occipital WM, the superior cerebellar peduncle, and bilateral anterior thalamic radiation. No significant associations between fractional anisotropy and the Scale for the Assessment and Rating of Ataxia were found.",
            "output": [
                "Does ataxia Severity correlate with White Matter Degeneration in Spinocerebellar Ataxia Type 7?"
            ]
        },
        {
            "id": "task847-9dd6901421db471893ab04a0c2e8da72",
            "input": "The gross majority of colorectal cancer cases results from aberrant Wnt/\u03b2-catenin signalling through adenomatous polyposis coli (APC) or CTNNB1 mutations. However, a subset of human colon tumours harbour, mutually exclusive with APC and CTNNB1 mutations, gene fusions in RSPO2 or RSPO3, leading to enhanced expression of these R-spondin genes. This suggested that RSPO activation can substitute for the most common mutations as an alternative driver for intestinal cancer. Involvement of RSPO3 in tumour growth was recently shown in RSPO3-fusion-positive xenograft models. The current study determines the extent into which solely a gain in RSPO3 actually functions as a driver of intestinal cancer in a direct, causal fashion, and addresses the in vivo activities of RSPO3 in parallel.', 'We generated a conditional Rspo3 transgenic mouse model in which the Rspo3 transgene is expressed upon Cre activity. Cre is provided by cross-breeding with Lgr5-GFP-Cre', 'Upon in vivo Rspo3 expression, mice rapidly developed extensive hyperplastic, adenomatous and adenocarcinomatous lesions throughout the intestine. RSPO3 induced the expansion of Lgr5",
            "output": [
                "Does rSPO3 expand intestinal stem cell and niche compartments and drives tumorigenesis?"
            ]
        },
        {
            "id": "task847-1470e519ee974bfb9607af8203e8da16",
            "input": "Endometrial cancer is a common gynecologic cancer whose incidence is increasing annually worldwide. Current methods to detect endometrial cancer are unreliable and biomarkers are unsatisfactory for screening. Cervical scrapings were reported as a potential source of material for molecular testing. DNA methylation is a promising cancer biomarker, but limited use for detecting endometrial cancer.', 'We analyzed two methylomics databases of endometrioid-type endometrial cancer. Using nonnegative matrix factorization algorithm clustered the methylation pattern and reduced the candidate genes. We verified in pools DNA from endometrial cancer tissues and cervical scrapings, and validated in 146 cervical scrapings from patients with endometrioid-type endometrial cancer (n = 50), uterine myoma (n = 40), and healthy controls (n = 56) using quantitative methylation-specific PCR (QMSP). The logistic regression was used to evaluate the performance of methylation signal and gene combination.', 'We filtered out 180 methylated genes, which constituted four consensus clusters. Serial testing of tissues and cervical scrapings detected 14 genes that are hypermethylated in endometrial cancer. Three genes, BHLHE22, CDO1, and CELF4, had the best performance. Individual genes were sensitivity of 83.7%-96.0% and specificity of 78.7%-96.0%. A panel comprising any two of the three hypermethylated genes reached a sensitivity of 91.8%, specificity of 95.5%, and odds ratio of 236.3 (95% confidence interval, 56.4-989.6). These markers were also applied to cervical scrapings of type II endometrial cancer patients, and detected in 13 of 14 patients.",
            "output": [
                "Does integrated Epigenomics Analysis reveal a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings?"
            ]
        },
        {
            "id": "task847-8c642573e7b448f59febb0445b07aeca",
            "input": "Research rationale: Evolution of fused petals (sympetaly) is considered to be an important innovation that has repeatedly led to increased pollination efficiency, resulting in accelerated rates of plant diversification. Although little is known about the underlying regulation of sympetaly, genetic pathways ancestrally involved in organ boundary establishment (e.g. CUP SHAPED COTYLEDON [CUC] 1-3 genes) are strong candidates. In sympetalous petunia, mutations in the CUC1/2-like orthologue NO APICAL MERISTEM (NAM) inhibit shoot apical meristem formation. Despite this, occasional 'escape shoots' develop flowers with extra petals and fused inter-floral whorl organs. Central methods: To To determine if petunia CUC-like genes regulate additional floral patterning, we used virus-induced silencing (VIGS) following establishment of healthy shoot apices to re-examine the role of NAM in petunia petal development, and uniquely characterise the CUC3 orthologue NH16.\", 'Confirming previous results, we found that reduced floral NAM/NH16 expression caused increased petal-stamen and stamen-carpel fusion, and often produced extra petals. However, further to previous results, all VIGS plants infected with NAM or NH16 constructs exhibited reduced fusion in the petal whorl compared to control plants.",
            "output": [
                "Are organ boundary NAC-domain transcription factors implicated in the evolution of petal fusion?"
            ]
        },
        {
            "id": "task847-99b1e522484a4bc3badcae50daaa9ba3",
            "input": "It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC). We investigated whether the \u03b1-fetoprotein (AFP) response is associated with survival in patients with advanced HCC treated with sorafenib.', 'We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6-8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors.', 'The median overall survival (OS) and progression-free survival (PFS) were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR) was identified in 5 patients (4.0%), stable disease (SD) in 65 patients (51.6%), and progressive disease (PD) in 57 patients (44.4%), respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response), together with Child-Pugh B, tumor diameter \u226510 cm, and portal vein invasion (all P<0.05), and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response), together with tumor diameter \u226510 cm and portal vein invasion (all P<0.05). SD or PR was more frequently found in AFP responders than in non-responders (72.1% vs 47.0%, respectively; P=0.007). In a sub-group with SD, OS (median 12.7 vs 5.8 months, respectively) and PFS (median 9.1 vs 3.7 months, respectively) were significantly longer in AFP responders than in non-responders (all P<0.05).",
            "output": [
                "Does early \u03b1-fetoprotein response predict survival in patients with advanced hepatocellular carcinoma treated with sorafenib?"
            ]
        },
        {
            "id": "task847-272ba7034858482aaefb573128adb9d7",
            "input": "Inflammation plays an important role in the pathophysiology of vascular disease. In this study, we aimed to evaluate the associations of neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) with left ventricular ejection fraction and ascending aorta diameter in patients with a bicuspid aortic valve (BAV).', 'One hundred and thirty-nine consecutive patients with the diagnosis of BAV were enrolled in the study. Complete blood counts were analyzed for neutrophil and lymphocyte levels and NLR. The subjects were separated into two groups based on their ascending aorta diameter. The patients with ascending aorta diameter equal to or above 3.9 cm were included in group 1 whereas those with ascending aorta diameter below 3.9 cm were included in group 2.', 'When the results were compared, it was demonstrated that there was a positive correlation between NLR and ascending aorta diameter (r: 0.485, P = 0.026), whereas there was a negative correlation between NLR and left ventricular end-diastolic diameter (r: 0.475, P = 0.030), left ventricular end-systolic diameter (r: 0.482, P = 0.027), and left ventricular ejection fraction (r: -0.467, P = 0.033) in BAV patients with ascending aorta dilatation (group 1).",
            "output": [
                "Is higher neutrophil to lymphocyte ratio related to a lower ejectionfraction in bicuspid aortic valve patients?"
            ]
        },
        {
            "id": "task847-c6a85bbbfcef48d98629e5ab3e30c654",
            "input": "Cardiovascular disease contributes to excess morbidity and mortality in HIV infection, and endothelial dysfunction may contribute to this pattern. We aimed to determine the endothelial function in treated and untreated HIV-infected individuals and investigate potential associations with viral replication, immune activation, coagulation, platelet function, and subclinical atherosclerosis.', 'Asymmetric dimethylarginine (ADMA, marker of endothelial dysfunction) and soluble CD14 (sCD14, marker of monocyte activation) were measured in plasma from two previously established cross-sectional cohorts: cohort A including 50 untreated and 50 antiretroviral therapy (ART)-treated HIV-infected individuals with previously assessed coagulation and platelet function and cohort B including 105 HIV-infected individuals on ART and 105 uninfected controls with previously assessed coronary artery calcium score, myocardial perfusion defects, and carotid intima-media thickness.', 'Concentrations of ADMA were higher in HIV-infected individuals compared with uninfected controls, and higher ADMA was found in ART-treated compared with untreated HIV-infected individuals. ADMA was associated with viral load, sCD14, D-dimer, and low CD4 T-cell count in untreated HIV infection. Only viral load remained significant in multivariate analyses. In ART-treated HIV-infected individuals, ADMA was not associated with coronary artery calcium score, myocardial perfusion defects, or intima-media thickness.",
            "output": [
                "Does marker of Endothelial Dysfunction Asymmetric Dimethylarginine be Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis?"
            ]
        },
        {
            "id": "task847-ac91638e3bae4d6d8a866c5955c6b3a9",
            "input": "Several strategies have been used to improve running economy (RE). Defined as the oxygen uptake required at a given submaximal running velocity, it has been considered a key aerobic parameter related to endurance running performance. In this context, concurrent strength and endurance training has been considered an effective method, although conclusions on the optimal concurrent training cannot yet be drawn.', 'To evaluate the effect of concurrent training on RE in endurance running athletes and identify the effects of subject characteristics and concurrent training variables on the magnitude of RE improvement.', 'We conducted a computerized search of the PubMed and Web of Science databases, and references of original studies were searched for further relevant studies. The analysis comprised 20 effects in 16 relevant studies published up to August 2015. The outcomes were calculated as the difference in percentage change between control and experimental groups (% change) and data were presented as mean \u00b1 95 % confidence limit. Meta-analyses were performed using a random-effects model and, in addition, simple and multiple meta-regression analyses were used to identify effects of age, training status, number of sessions per week, training duration, type of strength training, and neuromuscular performance on % change in RE.', 'The concurrent training program had a small beneficial effect on RE (% change = -3.93 \u00b1 1.19 %; p < 0.001). In addition, explosive (% change = -4.83 \u00b1 1.53; p < 0.001) and heavy weight (% change = -3.65 \u00b1 2.74; p = 0.009) training programs produced similar improvements in RE, while isometric training (% change = -2.20 \u00b1 4.37; p = 0.324) in selected studies did not induce a significant effect. The multiple linear meta-regression analysis showed that all the differences between % changes could be explained by including the above-mentioned characteristics of subjects and weight training program elements. This model showed that the magnitude of the % change in RE was larger for longer training duration (\u03b2 = -0.83 \u00b1 0.72, p = 0.02).",
            "output": [
                "Are explosive Training and Heavy Weight Training Effective for Improving Running Economy in Endurance Athletes : A Systematic Review and Meta-Analysis?"
            ]
        },
        {
            "id": "task847-eafc525bfaa34976a202c36a47637b3a",
            "input": "South Africa is undergoing epidemiological and nutrition transitions with associated increases in the incidence of overweight, obesity and diet-related chronic diseases. With the emergence of the nutrition transition in South Africa, there is an urgent need for interventions to prevent overweight and obesity in children and adolescents as risk factors for chronic diseases in adolescence may track throughout later life. This research explored the potential for faith-based organisations (FBOs) to be used as community organisations for overweight and obesity prevention interventions in adolescents by assessing the readiness of religious leaders to engage in such interventions.', 'Surveys and focus group discussions (FGDs) were conducted with 51 religious leaders in Johannesburg and Soweto. The Community Readiness Model (CRM) survey was chosen to determine the stage of readiness of this community regarding overweight and obesity prevention. Six different dimensions were assessed in the CRM (community efforts, knowledge of efforts, leadership, community climate, knowledge of the issue, resources). The surveys were scored according to the CRM protocol. The survey data were supplemented with findings from FGDs. Thematic analysis was used to analyse the FGDs.', 'The mean community readiness score was 2.57\\u2009\u00b1\\u20090.76 which equates with the \"denial/resistance stage\". The mean readiness score for resources was the highest of all the dimensions (3.77\\u2009\u00b1\\u20090.28), followed by knowledge of the issue (3.20\\u2009\u00b1\\u20090.51). The lowest score was seen for community knowledge of efforts (1.77\\u2009\u00b1\\u20091.50), followed by community climate (2.00\\u2009\u00b1\\u20090.64). FGDs helped interpret the CRM scores. FGDs showed that religious leaders were enthusiastic and recognised that their role was not limited solely to spiritual guidance and mentoring, but also to physical well-being.",
            "output": [
                "Is community readiness for adolescents ' overweight and obesity prevention low in urban South Africa : a case study?"
            ]
        },
        {
            "id": "task847-dba6141cbfc9410dbc7e95e9f0e1dcd1",
            "input": "Lamin A and C are nuclear filament proteins encoded by the LMNA gene. Mutations in the LMNA gene cause many congenital diseases known as laminopathies, including Emery-Dreifuss muscular dystrophy, Hutchinson-Gilford progeria syndrome, and familial dilated cardiomyopathy (DCM) with conduction disease. A missense mutation (N195K) in the A-type lamins results in familial DCM and sudden arrhythmic death.', 'The purpose of this study was to investigate the ion current mechanism of arrhythmia and DCM caused by the LaminA-N195K variant.', 'A homozygous mouse line expressing the Lmna-N195K mutation (Lmna', 'Both peak and late I",
            "output": [
                "Does inhibition of late sodium current attenuate ionic arrhythmia mechanism in ventricular myocytes expressing LaminA-N195K mutation?"
            ]
        },
        {
            "id": "task847-5ecf9b0cba0e4a65bb83307fc27dbfcc",
            "input": "Beta defensins are secreted from ovine oviduct epithelial cells (OOECs) in response to microbial infection, and are potential alternatives to antibiotic agents in the treatment of microorganism infection, particularly given the abuse of antibiotic agents and the increasing number of drug-resistant bacteria. The aberrant expression of defensins may result in disorders involving organ and oviduct inflammation, such as salpingitis.', 'In the present study, we investigated the effects of LPS on the mRNA expression levels of sheep \u03b2-defensin-1 (SBD-1) in ovine oviduct epithelial cells. The OOECs in vitro culturing system were established and treated with different concentrations of LPS for indicated time. In addition, MAPK inhibitors and TLR4 antibodies were pretreated to investigate the potential mechanism which involves in LPS regulating SBD-1 expression.', 'LPS markedly upregulated SBD-1 expression in a concentration- and time-dependent manner. Treatment with 100\\xa0ng/mL LPS resulted in the phosphorylation of JNK, ERK and P38 MAPK. Interestingly, the LPS stimulated SBD-1 expression was attenuated by pretreatment with the P38 MAPK inhibitors SB203580 and SB202190 but not the JNK inhibitor SP600125, while the ERK inhibitor PD98059 had a minor effect. Furthermore, treatment with a Toll-like receptor 4 (TLR4) neutralizing antibody significantly decreased P38 MAPK phosphorylation and LPS induced SBD-1 expression.",
            "output": [
                "Does lipopolysaccharide induce SBD-1 expression via the P38 MAPK signaling pathway in ovine oviduct epithelial cells?"
            ]
        },
        {
            "id": "task847-52093cf0208e482f8fc0722b4c0a27a3",
            "input": "We aimed to determine whether LR11 (low-density lipoprotein receptor with 11 binding repeats) is a potential key regulator of smooth muscle cell (SMC) proliferation during the progression of hypoxia-induced medial thickening in mice and whether sLR11 (soluble LR11) can serve as a biomarker in patients with pulmonary arterial hypertension.', 'The role of LR11 in pulmonary arterial hypertension was investigated using mouse and cell models of induced hypoxia. The expression of LR11 and of hypoxia-inducible factor-1\u03b1 was significantly increased in lung tissues from C57Bl/6 mice after 3 weeks of exposure to hypoxia compared with normoxia. Serum sLR11 levels were also increased. Physiological and histochemical analyses showed that increased right ventricular systolic pressure, right ventricular hypertrophy, and medial thickening induced under hypoxia in wild-type mice were attenuated in LR11(-/-) mice. The proliferation rates stimulated by hypoxia or platelet-derived growth factor-BB were attenuated in SMC derived from LR11(-/-) mice, compared with those from wild-type mice. Exogenous sLR11 protein increased the proliferation rates of SMC from wild-type mice. The expression of LR11 and hypoxia-inducible factor-1\u03b1 was increased in cultured SMC under hypoxic conditions, and hypoxia-inducible factor-1\u03b1 knockdown almost abolished the induction of LR11. Serum sLR11 levels were significantly higher in patients with, rather than without, pulmonary arterial hypertension. sLR11 levels positively correlated with pulmonary vascular resistance and mean pulmonary arterial pressure.",
            "output": [
                "Does deletion of LR11 attenuate Hypoxia-Induced Pulmonary Arterial Smooth Muscle Cell Proliferation With Medial Thickening in Mice?"
            ]
        },
        {
            "id": "task847-472c4cd1c315403a8c2b5d4239bc9d8d",
            "input": "Chemoresistance hinders curative cancer chemotherapy in osteosarcoma (OS), resulting in only an approximately 20\\xa0% survival rate in patients with metastatic disease at diagnosis. Identifying the mechanisms responsible for regulating chemotherapy resistance is crucial for improving OS treatment.', 'This study was performed in two human OS cell lines (the multi-chemosensitive OS cell line G-292 and the multi-chemoresistant OS cell line SJSA-1). The levels of miR-20a-5p and KIF26B mRNA expression were determined by quantitative real-time PCR. KIF26B protein levels were determined by western blot analysis. Cell viability was assessed by MTT assay. Apoptosis was evaluated by flow cytometry.', \"We found that miR-20a-5p was more highly expressed in G-292 cells than in SJSA-1 cells. Forced expression of miR-20a-5p counteracted OS cell chemoresistance in both cell culture and tumor xenografts in nude mice. One of miR-20a-5p's targets, kinesin family member 26B (KIF26B), was found to mediate the miR-20a-5p-induced reduction in OS chemoresistance by modulating the activities of the MAPK/ERK and cAMP/PKA signaling pathways.",
            "output": [
                "Does miR-20a-5p repress multi-drug resistance in osteosarcoma by targeting the KIF26B gene?"
            ]
        },
        {
            "id": "task847-23c6b9ef805449a496e34d20c1043b8e",
            "input": "Efavirenz frequently causes central nervous system (CNS) symptoms. We evaluated genetic associations with efavirenz discontinuation for CNS symptoms within 12 months of treatment initiation.', 'Patients had initiated efavirenz-containing regimens at an HIV primary care clinic in the Southeastern United States and had at least 12 months of follow-up data. Polymorphisms in CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide genotyping enabled adjustment for population stratification.', 'Among 563 evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%) for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS symptoms in slow versus extensive metabolizers was 4.9 [95% confidence interval (CI): 1.9-12.4; P=0.001]. This HR in Whites was 6.5 (95% CI: 2.3-18.8; P=0.001) and 2.6 in Blacks (95% CI: 0.5-14.1; P=0.27). Considering only slow metabolizers, the HR in Whites versus Blacks was 3.1 (95% CI: 0.9-11.0; P=0.081). The positive predictive value of slow metabolizer genotypes for efavirenz discontinuation was 27% in Whites and 11% in Blacks.",
            "output": [
                "Does pharmacogenetics of efavirenz discontinuation for reported central nervous system symptoms appear to differ by race?"
            ]
        },
        {
            "id": "task847-f15e38b5e6c94bfc9358921b42a93450",
            "input": "Data on antimicrobial prophylaxis for open fractures is limited, with many protocols based on expert recommendations. These protocols include aminoglycosides (AGs) for fractures with significant soft tissue injury, but these drugs are associated with acute kidney injury (AKI) in other settings; this risk has not been defined for open fracture prophylaxis.', 'We performed a retrospective study from May 2012 to October 2014 at our Level 1 trauma center. Patients with open fractures were evaluated for demographics, location/type of fracture, injury severity, and receipt of an AG. Outcomes included rates of AKI, infection, and mortality.', 'There were 167 patients with open fractures during the study period (119 males, mean age 42\\u2009\u00b1\\u200917 [standard deviation] years), with 80 (48%) receiving prophylactic gentamicin (AG+ group). The AG+ and AG- patients had similar fracture sites and Injury Severity Scores (ISSs) (12.6\\u2009\u00b1\\u20099.9 AG+ vs. 15.9\\u2009\u00b1\\u200913.2 AG-) but were more likely to have sustained blunt trauma (96% AG+ vs. 77%; p\\u2009<\\u20090.001) or received intravenous contrast medium \u226448\\u2009h from admission (75% AG+ vs. 56% AG-; p\\u2009=\\u20090.01). Gentamicin was not associated with AKI (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.020-2.44; p\\u2009=\\u20090.22), whereas hypotension on admission (OR 10.7; 95% CI 1.42-80.93; p\\u2009=\\u20090.02) and ISS (OR 1.1; 95% CI 1.01-1.20; p\\u2009=\\u20090.02) were both associated with AKI. Only four fracture site infections were identified, three in the AG+ group and one in the AG- group (3.8% vs. 1.1%; p\\u2009=\\u20090.27). The mortality rate was greater in the AG- group (3.8% vs. 12.6%; p\\u2009=\\u20090.04).",
            "output": [
                "Is prophylactic Gentamicin Associated with Acute Kidney Injury in Patients with Open Fractures?"
            ]
        },
        {
            "id": "task847-90318f8b11d54c92bf332f253e8288b0",
            "input": "The population analysis of cardiovascular risk and non-risk genetic variation can help to identify adaptive or random demographic processes that shaped coronary incidence variation across geography.', 'In this study, 114 single nucleotide polymorphisms and 17 tandem repeat polymorphisms from Nitric Oxide Synthases (NOS) regions were analyzed in 1686 individuals from 35 populations from Europe, North Africa, and the Middle East. NOS genes encode for key enzymes on nitric oxide availability, which is involved in several cardiovascular processes. These genetic variations were used to test for selection and to infer the population structure of NOS regions. Moreover, we tested whether the variation in the incidence of coronary events and in the levels of classical risk factors in 11 of these European populations could be explained by the population structure estimates.', 'Our results supported, first, the absence of clear signs of selection for NOS genetic variants associated with cardiovascular diseases, and second, the presence of a continuous genetic pattern of variation across European and North African populations without a Mediterranean barrier for gene flow. Finally, population structure estimates from NOS regions are closely correlated with coronary event rates and classical risk parameters (explaining 39-98%) among European populations.",
            "output": [
                "Does population structure from NOS genes correlate with geographical differences in coronary incidence across Europe?"
            ]
        },
        {
            "id": "task847-5ee6fef847084383a82964af58ce87a6",
            "input": "Both cadmium (Cd) and bisphenol A (BPA) are commonly encountered in humans' daily activities, but their combined genotoxic effects remain unclear.\", \"In the present study, we exposed a mouse embryonic fibroblast cell line (NIH3T3) to Cd for 24 h, followed by a 24 h BPA exposure to evaluate toxicity. The cytotoxicity was evaluated by viability with CCK-8 assay and lactate dehydrogenase (LDH) release. Reactive oxygen species (ROS) production was measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA). And DNA damage was measured by 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated H2AX (\u03b3H2AX) and the comet assay. The flow cytometry was used to detect cell cycle distribution, and apoptosis was determined by TUNEL assay and western blot against poly-ADP-ribose polymerase (PARP).\", 'The results showed that Cd or BPA treatments alone (with the exception of BPA exposure at 50 \u03bcM) did not alter cell viability. However, pre-treatment with Cd aggravated the BPA-induced reduction in cell viability; increased BPA-induced LDH release, ROS production, DNA damage and G2 phase arrest; and elevated BPA-induced TUNEL-positive cells and the expression levels of cleaved PARP. Cd exposure concurrently decreased the expression of 8-oxoguanine-DNA glycosylase-1 (OGG1), whereas OGG1 over-expression abolished the enhancement of Cd on BPA-induced genotoxicity and cytotoxicity.",
            "output": [
                "Does cadmium Exposure enhance Bisphenol A-Induced Genotoxicity through 8-Oxoguanine-DNA Glycosylase-1 OGG1 Inhibition in NIH3T3 Fibroblast Cells?"
            ]
        },
        {
            "id": "task847-1de00bd67e2d4580ac5e1610bf625d37",
            "input": "We have previously shown that the grape bioactive compound resveratrol (RSV) potentiates grape seed extract (GSE)-induced colon cancer cell apoptosis at physiologically relevant concentrations. However, RSV-GSE combination efficacy against colon cancer stem cells (CSCs), which play a key role in chemotherapy and radiation resistance, is not known.', 'We tested the anti-cancer efficacy of the RSV-GSE against colon CSCs using isolated human colon CSCs in vitro and an azoxymethane-induced mouse model of colon carcinogenesis in vivo.', 'RSV-GSE suppressed tumor incidence similar to sulindac, without any gastrointestinal toxicity. Additionally, RSV-GSE treatment reduced the number of crypts containing cells with nuclear \u03b2-catenin (an indicator of colon CSCs) via induction of apoptosis. In vitro, RSV-GSE suppressed - proliferation, sphere formation, nuclear translocation of \u03b2-catenin (a critical regulator of CSC proliferation) similar to sulindac in isolated human colon CSCs. RSV-GSE, but not sulindac, suppressed downstream protein levels of Wnt/\u03b2-catenin pathway, c-Myc and cyclin D1. RSV-GSE also induced mitochondrial-mediated apoptosis in colon CSCs characterized by elevated p53, Bax/Bcl-2 ratio and cleaved PARP. Furthermore, shRNA-mediated knockdown of p53, a tumor suppressor gene, in colon CSCs did not alter efficacy of RSV-GSE.",
            "output": [
                "Do grape compounds suppress colon cancer stem cells in vitro and in a rodent model of colon carcinogenesis?"
            ]
        },
        {
            "id": "task847-2765576a6c194f64bd13007a7edea288",
            "input": "Epidermal growth factor receptors (EGFR) are required for tumor promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by releasing pro-EGFR ligands. ADAM17 is regulated by G-protein-coupled receptors, including CXCR4. Here we investigated CXCR4-ADAM17 crosstalk and examined the role of ADAM17 in tumorigenesis.', 'We used CXCR4 inhibitor, AMD3100 and ADAM17 inhibitor, BMS566394 to assess CXCR4-ADAM17 crosstalk in colon cancer cells. We compared the expression of CXCR4 ligand, CXCL2, and ADAM17 in mice fed Western diet versus standard diet. Separately, mice were treated with marimastat, a broad-spectrum ADAM17 inhibitor, or AMD3100 to assess EGFR activation by ADAM17 and CXCR4. Using Apc-mutant Min mice, we investigated the effects of ADAM17/10 inhibitor INCB3619 on tumorigenesis. To assess the effects of colonocyte ADAM17, mice with ADAM17 conditional deletion were treated with azoxymethane (AOM). ADAM17 expression was also compared in colonocytes from primary human colon cancers and adjacent mucosa.', 'CXCL12 treatment activated colon cancer cell EGFR signals, and CXCR4 or ADAM17 blockade reduced this activation. In vivo, Western diet increased CXCL12 in stromal cells and TGF\u03b1 in colonocytes. Marimastat or AMD3100 caused >50% reduction in EGFR signals (P < 0.05). In Min mice, INCB3619 reduced EGFR signals in adenomas and inhibited intestinal tumor multiplicity (P < 0.05). In the AOM model, colonocyte ADAM17 deletion reduced EGFR signals and colonic tumor development (P < 0.05). Finally, ADAM17 was upregulated >2.5-fold in human malignant colonocytes.",
            "output": [
                "Is aDAM17 a Tumor Promoter and Therapeutic Target in Western Diet-associated Colon Cancer?"
            ]
        },
        {
            "id": "task847-ab95b8b7cd1144e4b5549cc363d9ad38",
            "input": "To investigate whether the use of continuous Pringle maneuver (PM) adversely impacts the outcome of patients with hepatocellular carcinoma (HCC).', 'From January 1989 to January 2011, 586 HCC patients who underwent curative resection in Peking Union Medical College Hospital were identified from the database. Continuous PM was performed in 290 patients (PM group), including 163 patients with a hepatic inflow occlusion time of <15 min (PM-1 group) and 127 with 15-30 min (PM-2 group). An additional 296 patients underwent partial hepatectomy without inflow occlusion (occlusion-free, OF group).', 'The PM group showed less estimated blood loss during hepatectomy than the OF group (P\\xa0=\\xa00.005) and the two groups experienced similar incidence of perioperative complications. There were no significant differences in either overall survival or disease-free survival (DFS) between the PM and OF groups (P\\xa0=\\xa00.117 and 0.291, respectively), and between the PM-1 and PM-2 groups (P\\xa0=\\xa00.344 and 0.103, respectively). Hepatic inflow occlusion and occlusion time were not independent risk factors for OS or DFS.",
            "output": [
                "Does continuous Pringle maneuver affect outcomes of patients with hepatocellular carcinoma after curative resection?"
            ]
        },
        {
            "id": "task847-8744a65c18544d588f303c0f7f6e707c",
            "input": "Long non-coding RNAs (LncRNAs) are an important class of widespread molecules involved in diverse biological functions, which are exceptionally expressed in numerous types of diseases. Currently, limited study on LncRNA in rheumatoid arthritis (RA) is available. In this study, we aimed to identify the specifically expressed LncRNA that are relevant to adjuvant-induced arthritis (AA) in rats, and to explore the possible molecular mechanisms of RA pathogenesis.', 'To identify LncRNAs specifically expressed in rheumatoid arthritis, the expression of LncRNAs in synoviums of rats from the model group (n=3) was compared with that in the control group (n=3) using Arraystar Rat LncRNA/mRNA microarray and real-time polymerase chain reaction (RT-PCR).', 'Up to 260 LncRNAs were found to be differentially expressed (\u22651.5-fold-change) in the synoviums between AA model and the normal rats (170 up-regulated and 90 down-regulated LncRNAs in AA rats compared with normal rats). Coding-non-coding gene co-expression networks (CNC network) were drawn based on the correlation analysis between the differentially expressed LncRNAs and mRNAs. Six LncRNAs, XR_008357, U75927, MRAK046251, XR_006457, DQ266363 and MRAK003448, were selected to analyze the relationship between LncRNAs and RA via the CNC network and GO analysis. Real-time PCR result confirmed that the six LncRNAs were specifically expressed in the AA rats.",
            "output": [
                "Does lncRNAs expression in adjuvant-induced arthritis rats reveal the potential role of LncRNAs contributing to rheumatoid arthritis pathogenesis?"
            ]
        },
        {
            "id": "task847-b399520bebbe47bcba804c0e9009d5ad",
            "input": "Atrial natriuretic peptide is a cardiac atrium-derived hormone and its cardioprotective effects have recently been confirmed, but the actual mechanism underlying these effects has not been well elucidated. In this study, we proposed that atrial natriuretic peptide achieves its effects in part via peroxisome proliferator activated receptor \u03b3, a nuclear receptor.', 'Hemodynamic data in swine heart ischemia-reperfusion model were measured under the conditions of no medication for control (Group N, n\\xa0=\\xa08) or that of carperitide (synthetic human atrial natriuretic peptide) systemic administration (Group A, n\\xa0=\\xa08). After 30\\xa0min of left anterior descending artery total occlusion and 4\\xa0h of reperfusion, peroxisome proliferator activated receptor \u03b3 mRNA and protein expressions in cardiac muscle were examined. The mRNA expression of Liver X receptor \u03b1, the downstream agent of peroxisome proliferator activated receptor \u03b3, was also evaluated. Creatine kinase-myocardial band and Troponin T elevations after reperfusion were evaluated as markers of cardiac damage.', 'The dP/dT decrease during reperfusion was ameliorated in Group A. Peroxisome proliferator activated receptor \u03b3 mRNA expression in Group A was significantly higher in ischemic area than that in Group N, although the difference was not significant in the marginal and non-ischemic areas. The peroxisome proliferator activated receptor \u03b3 protein expression in ischemic area was also significantly dominant in Group A.",
            "output": [
                "Does atrial natriuretic peptide induce peroxisome proliferator activated receptor \u03b3 during cardiac ischemia-reperfusion in swine heart?"
            ]
        },
        {
            "id": "task847-477360e871c64868b2139ab05e811000",
            "input": "The interleukin (IL)-10-production B cells play an important role in the pathogenesis of atherosclerosis (Asro) with unknown mechanism. Micro RNA (miR)-17-92 cluster has strong immune regulatory activities. This study tests a hypothesis that miR-17-92 cluster suppresses IL-10 expression in B cells of Asro patients.', 'Patients with Asro were recruited into this study. Peripheral blood samples were collected from the patients. B cells were isolated from the blood samples and analyzed to elucidate the role of miR-17-92 in the regulation of IL-10 expression.', 'Peripheral B cells from patients with Asro show lower levels of IL-10 than that from healthy subjects. The IL-10 expression in the B cells is negatively correlated with the expression of miR-19a in the B cells. The serum levels of tumor necrosis factor (TNF)-\u03b1, interferon (IFN)-\u03b3 and interleukin (IL)-4 in Asro patients were higher than healthy subjects. Exposure to TNF-\u03b1 or IFN-\u03b3 or IL-4 suppressed IL-10 expression in B cells via increasing the expression of miR-19a in B cells, which could be abolished by Inhibition of miR-19a.",
            "output": [
                "Does micro RNA-19a suppress IL-10 in peripheral B cells from patients with atherosclerosis?"
            ]
        },
        {
            "id": "task847-bf2ef4e9645c4f598ef1b50c819a1baf",
            "input": "Corticotropin-releasing hormone receptor 1 (CRH-R1) in the amygdala and the stria terminalis plays an important role in the activation of central stress circuits. Genetic factors may contribute to the hyperresponsiveness of these circuits in irritable bowel syndrome (IBS).', 'To determine if CRH-R1 SNPs are associated with: (1) a diagnosis of IBS, (2) gastrointestinal (GI) symptoms, and (3) acoustic startle response (ASR) to threat, which is mediated by the amygdala via CRH.', 'Three CRH-R1 SNPS (rs110402, rs242924, and rs7209436) were genotyped using salivary DNA from IBS and healthy control subjects (HCs). Eye blink ASR was obtained during safe (no shock), anticipation (abdominal shock may soon occur) and threat (abdominal shock likely) conditions in a subset of subjects. Associations between each SNP with IBS status, clinical traits and ASR were measured.', '235 IBS patients (mean age 37.5 yrs, 74% F) and 264 HCs (mean age 32.1 yrs, 70% F) were studied. Of these, 57 IBS and 41 HCs underwent the ASR protocol. The presence of IBS was associated with the major allele for all three CRH-R1 SNPs (p=0.009-0.025). Within IBS, the major allele for all three SNPs (p=0.017-0.065) was associated with GI symptom anxiety scores. Within subjects with at least one copy of the major allele for the CRH-R1 SNPs, IBS had significantly lower ASR compared to HCs during threat conditions (p=0.001-0.002). Within IBS, CRH-R1 SNPs were associated with a graded increase in ASR to threat (p=0.007-0.008).",
            "output": [
                "Are corticotropin-releasing hormone receptor 1 ( CRH-R1 ) polymorphisms associated with irritable bowel syndrome and acoustic startle response?"
            ]
        },
        {
            "id": "task847-abc6894763d6485eb7e0bd8f90c8dee6",
            "input": "Mesenchymal stromal cells are being investigated as a cell-based therapy for a number of disease processes, with promising results in animal models of systemic inflammation and sepsis. Studies are ongoing to determine ways to further improve the therapeutic potential of mesenchymal stromal cells. A gas molecule that improves outcome in experimental sepsis is carbon monoxide. We hypothesized that preconditioning of mesenchymal stromal cells with carbon monoxide ex vivo would promote further therapeutic benefit when cells are administered in vivo after the onset of polymicrobial sepsis in mice.', 'Animal study and primary cell culture.', 'Laboratory investigation.', 'BALB/c mice.', 'Polymicrobial sepsis was induced by cecal ligation and puncture. Mesenchymal stromal cells, mesenchymal stromal cells-conditioned with carbon monoxide, fibroblasts, or fibroblasts-conditioned with carbon monoxide were delivered by tail vein injections to septic mice. The mice were assessed for survival, bacterial clearance, and the inflammatory response during sepsis in each of the groups. Mesenchymal stromal cells were also assessed for their ability to promote bacterial phagocytosis by neutrophils, the production of specialized proresolving lipid mediators, and their importance for mesenchymal stromal cells function using gene silencing.', 'Ex vivo preconditioning with carbon monoxide allowed mesenchymal stromal cells to be administered later after the onset of sepsis (6\\u2009hr), and yet maintain their therapeutic effect with increased survival. Carbon monoxide preconditioned mesenchymal stromal cells were also able to alleviate organ injury, improve bacterial clearance, and promote the resolution of inflammation. Mesenchymal stromal cells exposed to carbon monoxide, with docosahexaenoic acid substrate, produced specialized proresolving lipid mediators, particularly D-series resolvins, which promoted survival. Silencing of lipoxygenase pathways (5-lipoxygenase and 12/15-lipoxygenase), which are important enzymes for specialized proresolving lipid mediator biosynthesis, resulted in a loss of therapeutic benefit bestowed on mesenchymal stromal cells by carbon monoxide.",
            "output": [
                "Does carbon Monoxide improve Efficacy of Mesenchymal Stromal Cells During Sepsis by Production of Specialized Proresolving Lipid Mediators?"
            ]
        },
        {
            "id": "task847-ba8a45b04b6a47fe841f0e92cb41dc91",
            "input": "This study investigated whether a 7-week yoga intervention could improve physical function, perceived stress, and mental/emotional wellness in elderly participants.', '8 participants (66.5\\xa0\u00b1\\xa00.3 years) attended 2 60-min Hatha yoga sessions/week for 7 weeks, and performed pre- and post-intervention assessments. Balance was assessed using a 5-test battery. Flexibility was measured by sit-and-reach and shoulder flexibility tests. Functional mobility tests included 8-ft up-and-go, 5 chair stands, and 4-m walk. Participants completed SF-12, exhaustion level, and Perceived Stress Scale (PSS) questionnaires.', 'SF-12 Mental Component Summary scores, exhaustion levels, and PSS scores improved post-intervention. No differences were found for physical function measures.",
            "output": [
                "Does yoga reduce perceived stress and exhaustion levels in healthy elderly individuals?"
            ]
        },
        {
            "id": "task847-8dad7eb9cf074190b1bfaa8c27a09f9f",
            "input": "Organ/space surgical site infections (OSIs) constitute an important postoperative metric. We sought to assess the impact of a previously described air leak test (ALT) on the incidence of OSI following major hepatectomies.', 'A single-institution hepatobiliary database was queried for patients who underwent a major hepatectomy without biliary-enteric anastomosis between January 2009 and June 2015. Demographic, clinicopathologic, and intraoperative data-including application of ALT-were analyzed for associations with postoperative outcomes, including OSI, hospital length of stay (LOS), morbidity and mortality rates, and readmission rates.', 'Three hundred eighteen patients were identified who met inclusion criteria, of whom 210 had an ALT. ALT and non-ALT patients did not differ in most disease and treatment characteristics, except for higher rates of trisegmentectomy among ALT patients (53 vs. 34\\xa0%, p\\u2009=\\u20090.002). ALT patients experienced lower rates of OSI and 90-day morbidity than non-ALT patients (5.2 vs. 13.0\\xa0%, p\\u2009=\\u20090.015 and 24.8 vs. 40.7\\xa0%, p\\u2009=\\u20090.003, respectively). In turn, OSI was the strongest independent predictor of longer LOS (OR\\u2009=\\u20094.89; 95\\xa0% CI, 2.80-6.97) and higher rates of 30- (OR\\u2009=\\u200932.0; 95\\xa0% CI, 10.9-93.8) and 45-day readmissions (OR\\u2009=\\u200929.4; 95\\xa0% CI, 10.2-84.6).",
            "output": [
                "Does rate of Organ Space Infection be Reduced with the Use of an Air Leak Test During Major Hepatectomies?"
            ]
        },
        {
            "id": "task847-b41020990aa7408bb37ce47d9e326154",
            "input": "Visceral and subcutaneous adipose tissue may contribute differentially to the septic inflammatory response. Accordingly, we tested the hypothesis that the ratio of visceral to subcutaneous adipose tissue is associated with altered sepsis outcome.', 'A retrospective analysis from a cohort of sepsis patients admitted between 2004 and 2009.', \"A mixed medical-surgical ICU at St. Paul's Hospital in Vancouver, Canada.\", 'Patients older than 16 years old who had sepsis and underwent abdominal CT scan (n = 257) for clinical reasons.', 'None.', 'We measured the visceral adipose tissue and subcutaneous adipose tissue areas and calculated the visceral adipose tissue-to-subcutaneous adipose tissue ratio. Visceral adipose tissue/subcutaneous adipose tissue was not correlated with body mass index (r = -0.015, p = NS) and therefore provides additional unique information independent of body mass index. Sepsis patients with higher visceral adipose tissue/subcutaneous adipose tissue had greater 90-day mortality than patients with lower visceral adipose tissue/subcutaneous adipose tissue (log-rank test, linear-by linear association p < 0.005). After adjustment for significant covariates using Cox regression, increased visceral adipose tissue/subcutaneous adipose tissue quartile was significantly associated with increased 90-day mortality with hazard ratios of 2.01 (95% CI, 1.01-3.99) for the third visceral adipose tissue/subcutaneous adipose tissue quartile compared with the first quartile and 2.32 (95% CI, 1.15-4.69) for the highest visceral adipose tissue/subcutaneous adipose tissue quartile when compared with the first quartile. Increased mortality for patients with higher visceral adipose tissue/subcutaneous adipose tissue was found for both patients with body mass index less than 25\\u2009kg/m (p = 0.004) and for body mass index greater than or equal to 25\\u2009kg/m (p = 0.023). Furthermore, we found significantly greater need for mechanical ventilation, renal replacement therapy, and ICU stay in patients in the highest visceral adipose tissue/subcutaneous adipose tissue quartile. The ratio of proinflammatory (interleukin-8) to anti-inflammatory (interleukin-10) plasma cytokine levels was greater in patients with higher visceral adipose tissue/subcutaneous adipose tissue than in those with lower visceral adipose tissue/subcutaneous adipose tissue (p = 0.043).",
            "output": [
                "Does increased Ratio of Visceral to Subcutaneous Adipose Tissue in Septic Patients be Associated With Adverse Outcome?"
            ]
        },
        {
            "id": "task847-8b6edb4df4c64947a8217a717af38454",
            "input": "Atrial fibrillation (AF) and chronic kidney disease (CKD) are closely related. The present study aimed to evaluate the association between estimated glomerular filtration rate (eGFR) and outcomes after cryoballoon catheter ablation for AF.', 'We included a total of 110 patients (64.0\u00b110.1 years, 64% men) with paroxysmal AF who underwent second-generation cryoballoon catheter ablation in this study. Recurrence and change in renal function after ablation were assessed by stratification of eGFR sub-groups.', 'During a mean follow-up period of 9 months, 20 (18%) patients had AF recurrence after the first catheter ablation procedure. Multivariate Cox regression analysis showed that eGFR [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.93-0.99, p=0.047], non-pulmonary vein (PV) ectopic beats at initial ablation (HR 2.92, 95% CI 1.03-8.27, p=0.043), and history of stroke (HR 7.47, 95% CI 2.30-24.2, p=0.001) were independent predictors of recurrence after the ablation. Among the CKD groups, recurrence was found in 7% (1/15), 12% (9/73), and 46% (10/22) of the eGFR \u226590mL/min/1.73m",
            "output": [
                "Is impaired renal function associated with recurrence after cryoballoon catheter ablation for paroxysmal atrial fibrillation : A potential effect of non-pulmonary vein foci?"
            ]
        },
        {
            "id": "task847-359702db272e4db78f81946c98df6c07",
            "input": "To determine the association between prophylactic plasma transfusion and periprocedural red blood cell (RBC) transfusion rates in patients with elevated international normalized ratio (INR) values undergoing interventional radiology procedures.', 'In this retrospective cohort study, adult patients undergoing interventional radiology procedures with a preprocedural INR available within 30 days of the procedure during a study period of January 1, 2009, to December 31, 2013, were eligible for inclusion. Baseline characteristics, coagulation parameters, transfusion requirements, and procedural details were extracted. Univariate and multivariable propensity-matched analyses were used to assess the relationships between prophylactic plasma transfusion and the outcomes of interest, with a primary outcome assessed a priori of RBC transfusion occurring during the procedure or within the first 24 hours postprocedurally.', 'A total of 18,204 study participants met inclusion criteria for this study, and 1803 (9.9%) had an INR of 1.5 or greater before their procedure. Of these 1803 patients, 196 patients (10.9%) received prophylactic plasma transfusion with a median time of 1.9 hours (interquartile range [IQR], 1.1-3.2 hours) between plasma transfusion initiation and procedure initiation. In multivariable propensity-matched analysis, plasma administration was associated with increased periprocedural RBC transfusions (odds ratio, 2.20; 95% CI, 1.38-3.50; P<.001) and postprocedural intensive care unit admission rates (odds\\xa0ratio, 2.11; 95% CI, 1.41-3.14; P<.001) as compared with those who were not transfused preprocedurally. Similar relationships were seen at higher INR thresholds for plasma transfusion.",
            "output": [
                "Is prophylactic Plasma Transfusion Before Interventional Radiology Procedures Associated With Reduced Bleeding Complications?"
            ]
        },
        {
            "id": "task847-4d63207a3d0140aeab1154cbfe440f6d",
            "input": "To investigate the recent incidence of T1D in a US Midwestern county to determine whether this increase has been sustained and compare it with the incidence of celiac disease (CD) and also investigate the prevalence of CD, an associated autoimmune disease, within the cohort.', 'A broad search strategy was used to identify all incident cases of T1D in Olmsted County, Minnesota, between January 1, 1994, and December 31, 2010, using the Rochester Epidemiology Project. Diagnosis and residency status were confirmed through the medical record. Incidence rates were directly standardized to the 2010 US population. Poisson regression was used to test for a change in incidence rate. Clinical charts were reviewed to confirm case status.', 'There were 233 incident cases of T1D. Directly adjusting for age and sex with respect to the 2010 US white population, the overall annual incidence of T1D was 9.2 (95% CI, 8.0-10.4) per 100,000 people per year among all ages and 19.9 (95% CI, 16.6-23.2) per 100,000 people per year for those younger than 20 years. There was no significant increase in the incidence of T1D over time (P=.45). Despite the overall stability in annual incidence, there was an initial increasing trend followed by a plateau. Of the 109 patients with T1D (47%) tested for CD, 12% (13) had biopsy-proven CD.",
            "output": [
                "Is incidence of Type 1 Diabetes Increasing in a Population-Based Cohort in Olmsted County , Minnesota , USA?"
            ]
        },
        {
            "id": "task847-c95032b49a3b49edb1356e91a63fb36d",
            "input": "There is no consensus about the ideal method for diagnosis in patients who have already undergone endoscopic ultrasound fine needle aspiration (EUS-FNA), and the inconclusive material is often obtained. The aim was to evaluate the diagnostic yield of the second EUS-FNA of pancreatic lesions.', 'A retrospective analysis of prospectively collected data of patients with EUS-FNA of pancreatic lesions is performed. All patients who underwent more than one EUS-FNA for the evaluation of suspected pancreatic cancer over a 7-year period were included in the analysis.', 'A total of 296 EUS-FNAs of the pancreas were performed in 257 patients. The diagnostic yield with the first EUS-FNA was 78.6% (202/257). Thirty-nine (13.3%) FNAs were repeated in 34 patients; 17 (50%) patients were women. The mean \u00b1 standard deviation (SD) age was 58.8 \u00b1 16.1 years. The location of the lesions in the pancreatic gland, from which the second biopsies were taken, was head of the pancreas, n = 28 (82.4%), body of the pancreas, n = 3 (8.8%), and tail, n = 3 (8.8%). The mean \u00b1 SD of the size of the lesion was 36.3 \u00b1 14.6 mm. The second EUS-FNA was more likely to be positive for diagnosis in patients with an \"atypical\" histological result in the first EUS-FNA (odds ratio [OR]: 4.04; 95% confidence interval [CI]: 0.9-18.3), in contrast to patients with a first EUS-FNA reported as \"normal\" (OR: 0.21; 95% CI: 0.06-0.71). Overall, the diagnostic yield of the second EUS-FNA was 58.8% (20/34) with an increase to 86.3% overall (222/257).",
            "output": [
                "Is repeat endoscopic ultrasound fine needle aspiration after a first negative procedure useful in pancreatic lesions?"
            ]
        },
        {
            "id": "task847-738e918c261740a199c17c76790eef67",
            "input": "Effective use of the convex curvilinear ultrasound bronchoscope in the esophagus (EUS-B) for fine needle aspiration biopsy of mediastinal structures is now well described. In contrast, there is little to no reporting, depending on the site of EUS-B for access to sub-diaphragmatic structures. Our practice has been accessing sub-diaphragmatic sites for years. This review documents our experience with EUS-B to biopsy liver, left adrenal glands, and coeliac lymph nodes.', \"After Institutional Review Board's approval, all endosonographic procedures performed by interventional pulmonary between July 2013 and June 2015 were reviewed. Those including biopsy of sub-diaphragmatic sites were then selected for analysis.\", 'Over the study interval, 45 sub-diaphragmatic biopsy procedures (25 left adrenal glands, 7 liver, and 13 celiac node) were performed with EUS-B. In all cases, cellular adequacy was present, and samples were large enough for immunohistochemistry and any relevant ancillary studies. Metastatic malignancy was documented in 58% of cases, 16% of cases contained benign diagnostic findings, and in 27% of cases, normal organ tissue was documented. There were no complications.",
            "output": [
                "Is exploration under the dome : Esophageal ultrasound with the ultrasound bronchoscope indispensible?"
            ]
        },
        {
            "id": "task847-e2d01396b7174ccaa4094868601dfd2a",
            "input": "Visit-to-visit variability in low-density lipoprotein-cholesterol (LDL-C) was found to be a novel predictor of adverse cardiac events. Obstructive sleep apnea (OSA), an emerging cardiovascular risk factor, is characterized by sympathetic activation and increased oxidative stress which are regulators of LDL-C metabolism. We hypothesized that OSA was associated with LDL-C variability.', 'We prospectively recruited 190 patients with coronary artery disease for an overnight sleep study. Statin was prescribed upon discharge for 186 patients. Serum LDL-C levels were measured at clinic every 3 to 6\\xa0months. Severity of OSA (on the basis of apnea-hypopnea index (AHI)) was correlated with visit-to-visit LDL-C variability (on the basis of variation independent of mean (VIM)) in outpatient clinic.', \"The mean AHI was 21.9\\u2009\u00b1\\u200918.9. Using an AHI cut-off of 5-14.9, 15-29.9, and \u226530, the prevalence of mild, moderate, and severe OSA was 26.3, 18.9, and 27.4\\xa0%, respectively. After 53.2\\u2009\u00b1\\u200925.3\\xa0months, LDL-C was recorded over 8.1\\u2009\u00b1\\u20094.2 measurements. VIM positively correlated with AHI (Pearson's r\\u2009=\\u20090.183, p\\u2009=\\u20090.016), but not body mass index, baseline and mean follow-up LDL-C levels, and number of LDL-C measurements. In multiple linear regression analysis, AHI remained an independent predictor of VIM after adjusting for diabetes mellitus and hyperlipidemia. A 10-unit rise in AHI led to a 3.8\\xa0% increase in VIM (95\\xa0% CI 0.1 to 7.4\\xa0%; p\\u2009=\\u20090.044).",
            "output": [
                "Is obstructive sleep apnea associated with visit-to-visit variability in low-density lipoprotein-cholesterol in patients with coronary artery disease?"
            ]
        },
        {
            "id": "task847-8f4259742079478189db1481f31e44d7",
            "input": "Preterm delivery and sub-optimal fetal growth are associated with each other and affect both mother and infant. Our aim was to determine (i) whether there are detectable differences in DNA methylation between early and late gestation and (ii) whether changes in DNA methylation from entry are associated with spontaneous preterm delivery with and without reduced fetal growth.', 'We conducted a case-control study nested within a large prospective cohort. Gene specific methylation was measured by Methyl-Profiler PCR Array in a Human Breast Cancer Signature Panel of 24 genes from maternal peripheral leukocytes genomic DNA at entry and 3', 'There was significantly decrease in DNA methylation in 15 of 24 genes during the 3",
            "output": [
                "Is spontaneous Preterm Delivery , Particularly with Reduced Fetal Growth , Associated with DNA Hypomethylation of Tumor Related Genes?"
            ]
        },
        {
            "id": "task847-c08865aa5cad415890acf647661c568e",
            "input": "Early parenthood is a time of chronic sleep disturbance and also of heightened depression risk. Poor sleep quality has been identified both as a predictor of postpartum depressive symptoms and as a consequence.', 'This study sought to clarify causal pathways linking sleep and postpartum depression via longitudinal path modeling. Sleep quality at 6\\xa0months postpartum was hypothesized to exacerbate depressive symptoms from 1\\xa0month through 1\\xa0year postpartum in both mothers and fathers. Within-couple associations between sleep and depression were also tested.', 'Data were drawn from a low-income, racially and ethnically diverse sample of 711 couples recruited after the birth of a child. Depressive symptoms were assessed at 1, 6, and 12\\xa0months postpartum, and sleep was assessed at 6\\xa0months postpartum.', \"For both partnered mothers and fathers and for single mothers, depressive symptoms at 1\\xa0month postpartum predicted sleep quality at 6\\xa0months, which in turn predicted depressive symptoms at both 6 and 12\\xa0months. Results held when infant birth weight, breastfeeding status, and parents' race/ethnicity, poverty, education, and immigration status were controlled. Mothers' and fathers' sleep quality and depressive symptoms were correlated, and maternal sleep quality predicted paternal depressive symptoms both at 6 and at 12\\xa0months.",
            "output": [
                "Does sleep Quality predict Persistence of Parental Postpartum Depressive Symptoms and Transmission of Depressive Symptoms from Mothers to Fathers?"
            ]
        },
        {
            "id": "task847-6beb24a85103438380718db3023cbf22",
            "input": "Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat/cholesterol on the development of dyslipidemia and NAFLD.', 'Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4\\xa0% fat), a very high-sucrose diet (vHS: 4\\xa0% fat, 25\\xa0% sucrose), a high-fat diet (HF: 20\\xa0% fat, 0.35\\xa0% cholesterol), a high-fat/high-sucrose diet (HFHS: 20\\xa0% fat, 15\\xa0% sucrose, 0.35\\xa0% cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20\\xa0% fat, 25\\xa0% sucrose, 0.35\\xa0% cholesterol) for 16 and 25\\xa0weeks.', 'All three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p\\u2009<\\u20090.0001), LDL-C (p\\u2009<\\u20090.0001) and VLDL-C (p\\u2009<\\u20090.05) compared to control and vHS. Contrary to this, plasma triglycerides were increased in control and vHS compared to high-fat fed animals (p\\u2009<\\u20090.01), while circulating levels of free fatty acids were even between groups. Histological evaluation of liver sections revealed non-alcoholic steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in high-fat fed animals. Accordingly, hepatic triglycerides (p\\u2009<\\u20090.05) and cholesterol (p\\u2009<\\u20090.0001) was increased alongside elevated levels of alanine and aspartate aminotransferase (p\\u2009<\\u20090.01) compared to control and vHS.",
            "output": [
                "Is high-fat but not sucrose intake essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs?"
            ]
        },
        {
            "id": "task847-9fd90782feec4505b4f1ab2ec5457b04",
            "input": "Patients admitted with Clostridium difficile infection are managed in a variety of settings. If their care is inadequate, these patients can rapidly deteriorate.', 'The purpose of this study was to evaluate whether mortality for patients admitted with C difficile differed between medical and general/colorectal surgery services.', 'This was a retrospective cohort study with multivariable logistic regression used to evaluate the effect of admitting service on in-hospital mortality rates, with propensity score matching used to validate this relationship.', 'The study was conducted at a single, tertiary care center.', 'Inpatients with a positive C difficile stool test within 24 hours of admission to medical or surgical services were identified (2005-2015) using institutional electronic data sources.', 'We measured inpatient mortality rate.', 'Of 1175 patients, 985 (83%) were admitted to medical services, whereas 190 (17%) were admitted by surgeons. Medical patients were older (63.9 vs 58.9 years; p = 0.001) and had a mean of 0.6 additional comorbidities (p < 0.001); cohorts were similar regarding vasopressors, peak white blood cell counts, and rate of intensive care unit admissions. Mortality was lower among surgery patients (2.6% vs 6.8%; p = 0.028), and logistic regression demonstrated lower odds of mortality for this group OR = 0.18 (95% CI, 0.05-0.58)). After propensity score matching for age, comorbidities, and severity of disease, this difference was confirmed (2.6% vs. 9.5%). A higher incidence of total colectomy for surgery patients (14.2% vs 0.4%) was a causal factor in their longer lengths of stay and higher total hospital costs. The time between orders for stool testing and metronidazole therapy was shorter in the surgery group (1.8 vs 3.8 hours; p = 0.002), although this trend was not observed with vancomycin therapy.",
            "output": [
                "Does clostridium difficile Infection be Associated With Lower Inpatient Mortality When Managed by GI Surgeons?"
            ]
        },
        {
            "id": "task847-27acfe81149c4d89a36035798a5a350e",
            "input": "Blood oxygen level-dependent (BOLD) MRI has been effectively used to monitor changes in renal oxygenation. However, R2* (or T2*) is not specific to blood oxygenation and is dependent on other factors. This study investigates the use of a statistical model that takes these factors into account and maps BOLD MRI measurements to blood pO2.', \"Spin echo and gradient echo images were obtained in six Sprague-Dawley rats and R2 and R2* maps were computed. Measurements were made at baseline, post-nitric oxide synthase inhibitor (L-NAME), and post-furosemide administration. A simulation of each region was performed to map R2' (computed as R2*-R2) to blood pO2.\", 'At baseline, blood pO2 in the outer medulla was 30.5\\u2009\u00b1\\u20091.2 mmHg and 51.9\\u2009\u00b1\\u20095.2 mmHg in the cortex, in agreement with previous invasive studies. Blood pO2 was found to decrease within the outer medulla following L-NAME (P\\u2009<\\u20090.05) and increase after furosemide (P\\u2009<\\u20090.05). Blood pO2 in the cortex increased following furosemide (P\\u2009<\\u20090.05).",
            "output": [
                "Is bOLD quantified renal pO2 sensitive to pharmacological challenges in rats?"
            ]
        },
        {
            "id": "task847-bd587358a85a484185dc5328d721a906",
            "input": "The association between periodontitis and atherosclerotic cardiovascular diseases (ACVD) has been established in some modestly sized studies (<10\\u2005000). Rarely, however, periodontitis has been studied directly; often tooth loss or self-reported periodontitis has been used as a proxy measure for periodontitis. Our aim is to investigate the adjusted association between periodontitis and ACVD among all individuals registered in a large dental school in the Netherlands (Academic Centre for Dentistry Amsterdam (ACTA)).', 'Anonymised data were extracted from the electronic health records for all registered patients aged >35\\u2005years (period 1998-2013). A participant was recorded as having periodontitis based on diagnostic and treatment codes. Any affirmative answer for cerebrovascular accidents, angina pectoris and/or myocardial infarction labelled a participant as having ACVD. Other risk factors for ACVD, notably age, sex, smoking, diabetes, hypertension, hypercholesterolaemia and social economic status, were also extracted. Logistic regression analyses were used to evaluate the adjusted associations between periodontitis and ACVD.', '60\\u2005174 individuals were identified; 4.7% of the periodontitis participants (455/9730) and 1.9% of the non-periodontitis participants (962/50\\u2005444) reported ACVD; periodontitis showed a significant association with ACVD (OR 2.52; 95% CI 2.3 to 2.8). After adjustment for the confounders, periodontitis remained independently associated with ACVD (OR 1.59; 95% CI 1.39 to 1.81). With subsequent stratification for age and sex, periodontitis remained independently associated with ACVD.",
            "output": [
                "Is periodontitis an independent risk indicator for atherosclerotic cardiovascular diseases among 60 174 participants in a large dental school in the Netherlands?"
            ]
        },
        {
            "id": "task847-ef29c42d476343a991743a1586cadd97",
            "input": "The protective effects of grapefruit-derived naringin against HIV-1 Protease Inhibitors (PIs)-associated oxidative damage to pancreatic \u03b2-cells and apoptosis were investigated in RIN-5F cells in culture.', 'Cells in culture medium were challenged with 11-25\\xa0mM glucose with or without nelfinavir (1-10\\xa0\u03bcM), saquinavir (1-10\\xa0\u03bcM) and atazanavir (5-20\\xa0\u03bcM), respectively for 24\\xa0h to determine insulin secretion. The cells were further treated with nelfinavir (10\\xa0\u03bcM), saquinavir (10\\xa0\u03bcM), atazanavir (20\\xa0\u03bcM) with and without naringin or glibenclamide (10\\xa0\u03bcM) for 24\\xa0h to determine insulin secretion, lipid peroxidation, Superoxide Dismutase (SOD) activity, glutathione (GSH) levels, ATP production and caspase-3 and-9 activities, respectively.', 'Glucose-dependent insulin secretion was significantly reduced by PIs in a concentration-dependent manner. Treatment with either naringin or glibenclamide significantly reduced lipid peroxidation, Superoxide Dismutase (SOD) activities and also increased glutathione (GSH) and ATP levels in the cells that were treated with PIs. Furthermore, naringin or glibenclamide significantly reduced caspase-3 and caspase-9 activities in cells that were treated with PIs.",
            "output": [
                "Does naringin protect against HIV-1 protease inhibitors-induced pancreatic \u03b2-cell dysfunction and apoptosis?"
            ]
        },
        {
            "id": "task847-50890800d66d4facab47918bd3d7f2ee",
            "input": "Lung adenocarcinomas are a heterogeneous set of diseases with distinct genetic and histologic characteristics. Besides the discovery of oncogenic mutations and introduction of the histologic classifications (2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society and 2015 WHO), increasing evidence has linked this intertumor heterogeneity\\xa0to the lung lineage-specific pathways and lineage genes. Therefore, in this study, we assessed the gene expression of identified lung lineage genes to study their role in distinguishing lung adenocarcinoma diversities.', 'A total of 278 surgically resected lung adenocarcinomas were included. Each case was evaluated for genetic mutations and histologic classification. Lineage genes associated with respiratory tract differentiation (NK2 homeobox 1 gene [NKX2-1], GATA protein binding 6 gene [GATA6], foxhead box J1 gene [FOXJ1], and SAM pointed domain containing ETS transcription factor gene [SPDEF]) and stem/basal-like status (inhibitor of DNA binding 2, HLH protein gene [ID2], POU class 5 homeobox 1 gene [POU5F1], SRY-box 2 gene [SOX2], and v-myc avian myelocytomatosis viral oncogene homolog gene [MYC]) were selected. mRNA expression of these genes in each tumor sample was assessed by quantitative real-time polymerase chain reaction and normalized to paired normal lung tissue.', 'Distinct lineage gene expressions were found on the basis of genetic and histologic diversities. Expression of NKX2-1, GATA6, FOXJ1, and POU5F1 exhibited a significant linear relationship across histologic subgroups that was independent of genetic mutation status. Expression levels of NKX2-1 and POU5F1 were also associated with EGFR mutation status, independent of histologic subtypes. Further analysis revealed that the overexpression of SPDEF defined longer relapse-free survivals, especially in stage I disease.",
            "output": [
                "Do the Histologic Classifications of Lung Adenocarcinomas Are Discriminable by Unique Lineage Backgrounds?"
            ]
        },
        {
            "id": "task847-5c40ea74050e487fbc8c2aea7bb44e58",
            "input": "Cardiac tests for diagnosing myocarditis lack sensitivity or specificity. We hypothesized that contrast-enhanced ultrasound molecular imaging could detect myocardial inflammation and the recruitment of specific cellular subsets of the inflammatory response in murine myocarditis.', 'Microbubbles (MB) bearing antibodies targeting lymphocyte CD4 (MBCD4), endothelial P-selectin (MBPSel), or isotype control antibody (MBIso) and MB with a negative electric charge for targeting of leukocytes (MBLc) were prepared. Attachment of MBCD4 was validated in vitro using murine spleen CD4+ T cells. Twenty-eight mice were studied after the induction of autoimmune myocarditis by immunization with \u03b1-myosin-peptide; 20 mice served as controls. Contrast-enhanced ultrasound molecular imaging of the heart was performed. Left ventricular function was assessed by conventional and deformation echocardiography, and myocarditis severity graded on histology. Animals were grouped into no myocarditis, moderate myocarditis, and severe myocarditis. In vitro, attachment of MBCD4 to CD4+ T cells was significantly greater than of MBIso. Of the left ventricular ejection fraction or strain and strain rate readouts, only longitudinal strain was significantly different from control animals in severe myocarditis. In contrast, contrast-enhanced ultrasound molecular imaging showed increased signals for all targeted MB versus MBIso both in moderate and severe myocarditis, and MBCD4 signal correlated with CD4+ T-lymphocyte infiltration in the myocardium.",
            "output": [
                "Does noninvasive Contrast-Enhanced Ultrasound Molecular Imaging detect Myocardial Inflammatory Response in Autoimmune Myocarditis?"
            ]
        },
        {
            "id": "task847-89eb92d416b54934863d5374c9874c13",
            "input": "The endogenous opioid system has been reportedly implicated in tobacco/nicotine dependence.', 'We examined the genetic effects of eight SNPs in opioid receptor-related genes on smoking status and smoking-related traits in Japanese.', 'The genotypic and allelic variations of the rs2229205 SNP in the OPRL1 gene were significantly associated with smoking status, but no significant differences were found in the genetic variations of any of the SNPs with regard to smoking-related traits. The rs2229205 SNP did not show high linkage disequilibrium with the other SNPs in the linkage disequilibrium block that contained the SNP.",
            "output": [
                "Is nociceptin/orphanin FQ receptor gene variation associated with smoking status in Japanese?"
            ]
        },
        {
            "id": "task847-a35994b34d0b4a82abc332c068a5648d",
            "input": "To investigate the prevalence and temporal development of N-methyl-d-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE).', \"This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3\\xa0weeks and after 3\\xa0months. Anti-NMDAR IgG was detected with HEK293\\xa0cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24\\xa0months' follow-up.\", \"Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3\\xa0months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24\\xa0months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p=0.018).",
            "output": [
                "Does n-methyl-d-aspartate receptor autoimmunity affect cognitive performance in herpes simplex encephalitis?"
            ]
        },
        {
            "id": "task847-b0ab5008b6e3425d85133fb21d9e56aa",
            "input": "Viral causes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are well recognised but only recently have rapid tests become available.', 'To identify respiratory viruses in the general population and those associated with hospitalisation in AECOPD using polymerase chain reaction (PCR) on nasopharyngeal aspirate (NPA), and the relationship between symptoms, viral detection and inflammatory markers.', 'A review of viruses detected in the general population in a health district between August 2014 and July 2015, using multiplex PCR for viruses from NPA samples. In addition, a single hospital, retrospective audit of patients admitted with suspected AECOPD was conducted.', 'Of the 8811 NPA tested, 5599 (64%) were positive for at least one virus and 2069 of these were obtained from adults. In adults, the most common viruses identified were Influenza A (31%), Rhinovirus (27%) and respiratory syncytial virus A/B (10%). Most patients with AECOPD (102 of 153) had NPA sent for viral PCR testing and 59 (58%) were positive. The most common viruses identified were Influenza A (31%), Rhinovirus (24%) and respiratory syncytial virus A/B (17%) with co-infecting bacteria cultured in 22 sputum samples. Patients with influenza-like symptoms were more likely to have a positive viral PCR than those without symptoms (P < 0.004). The median C-reactive protein on admission was lower in the virus-infected than uninfected AECOPD (28 vs 60 mg/L, P < 0.026).",
            "output": [
                "Are viruses frequently present as the infecting agent in acute exacerbations of chronic obstructive pulmonary disease in patients presenting to hospital?"
            ]
        },
        {
            "id": "task847-1303cdeb85f547f1bdc2459014c83a6c",
            "input": "The purpose of the present study was to investigate the potential signal mechanism of tissue factor (TF)\\xa0in the regulation of the expression of vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (ARPE-19) cells.', 'An in vitro RPE cell chemical hypoxia model was established by adding cobalt chloride (CoCl2) in the culture medium. The irritative concentration of CoCl2 was determined with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay kit. VEGF production in ARPE-19 cells was measured with enzyme-linked immunosorbent assay (ELISA) and western blotting. The Wnt signaling pathway-associated molecules, including phospho-glycogen synthase kinase 3\u03b2 (p-GSK3\u03b2), GSK3\u03b2, p-\u03b2-catenin and \u03b2-catenin, were detected with western blotting. pEGFP-N3-hTF was constructed and verified with digestion of the restriction enzyme and sequencing analysis. Human TF overexpression and silencing plasmids were transfected into the ARPE-19 cells to clarify the causal relationship between TF and VEGF expression. The Transwell coculture system of ARPE-19 cells and RF/6A rhesus macaque choroid-retinal endothelial cells was performed to evaluate cell invasion and tube formation ability.', 'Our anoxic model of ARPE-19 cells showed that TF expression was upregulated in accordance with variations in hypoxia-inducible factor 1-alpha (HIF-1\u03b1) and VEGF levels. Silencing and overexpression of TF decreased and increased VEGF expression, respectively. The Wnt/\u03b2-catenin signaling pathway played an important role in this effect. Results from the ARPE-19 cell and RF/6A cell coculture system showed that the enhancement of TF expression in the ARPE-19 cells led to significantly faster invasion and stronger tube-forming ability of the RF/6A cells, while siRNA-mediated TF silencing caused the opposite effects. Pharmacological disruption of Wnt signaling IWR-1-endo inhibited the effects compared to the TF-overexpressing group, indicating the importance of the Wnt/\u03b2-catenin signaling pathway in the process of TF-induced VEGF expression and angiogenesis.",
            "output": [
                "Does tissue factor induce VEGF expression via activation of the Wnt/\u03b2-catenin signaling pathway in ARPE-19 cells?"
            ]
        },
        {
            "id": "task847-61a720abc9d04a8c9bdd00484f6390e9",
            "input": "This study aims to evaluate the relationship between serum thymus and activation-regulated chemokine (TARC) levels with various clinicopathological conditions in patients with drug eruptions. The value of TARC in diagnosing drug-induced hypersensitivity syndrome (DIHS) was also examined.', 'Study participants included 84 patients who presented with generalized eruptions suspected to be drug-related, including DIHS, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), maculopapular exanthema (MPE), erythema multiforme (EM), erythroderma, and toxicoderma. The correlation coefficients between serum TARC levels and clinical parameters in peripheral blood samples were calculated.', 'Serum TARC levels in patients with DIHS were higher than those found in patients with SJS/TEN, MPE, EM, and toxicoderma. TARC levels had 100% sensitivity and 92.3% specificity in diagnosing DIHS, with a threshold value of 13,900\\xa0pg/mL. Serum TARC levels positively correlated with age, white blood cell (WBC) count, neutrophil count, eosinophil count, monocyte count, atypical lymphocyte (Aty-ly) count, serum blood urea nitrogen (BUN) levels, and creatinine (Cr) levels. It negatively correlated with serum total protein (TP), albumin (Alb), and estimated glomerular filtration rate (eGFR). Among these clinical parameters, blood eosinophil counts were most strongly correlated with serum TARC levels, with a correlation coefficient of 0.53.",
            "output": [
                "Are serum TARC levels strongly correlated with blood eosinophil count in patients with drug eruptions?"
            ]
        },
        {
            "id": "task847-470c5a4dff724c02964fd0752c4a8f8d",
            "input": "MicroRNAs are non-coding small RNAs that regulate expression of target genes by binding to 3' untranslated regions. In this study, we used bronchial epithelial cells to investigate in\\xa0vitro the role of the microRNA miR-155 in the expression of chemokines associated with airway inflammation. miR-155 has previously been reported to regulate allergic inflammation.\", 'BEAS-2B bronchial epithelial cells were cultured and transfected with mimic or inhibitor oligonucleotides to overexpress or downregulate miR-155, as confirmed by real-time PCR. Cells were then stimulated with tumor necrosis factor-alpha, interleukin-13 (IL-13), and a double stranded RNA that binds Toll-like receptor 3. Expression and secretion of the chemokines CCL5, CCL11, CCL26, CXCL8, and CXCL10 were then quantified by real-time PCR and ELISA, respectively. Phosphorylation of signal transducer and activator of transcription 6 (STAT6), a target of the IL-13 receptor, was analyzed by ELISA.', 'miR-155 overexpression significantly suppressed IL-13-induced secretion of CCL11 and CCL26. These effects were specific, and were not observed for other chemokines, nor in cells with downregulated miR-155. miR-155 overexpression also suppressed CCL11 and CCL26 mRNA, but did not affect expression of the IL-13 receptor or phosphorylation of STAT6.",
            "output": [
                "Does overexpression of microRNA-155 suppress chemokine expression induced by Interleukin-13 in BEAS-2B human bronchial epithelial cells?"
            ]
        },
        {
            "id": "task847-60e6af9bca854622a12c08d7bc6f0762",
            "input": "Microbiota has been suggested in promoting chronic inflammation in human tissues which, in turn, promotes tumor development. This study tests a hypothesis that high-risk human papillomavirus (HR-HPV) infection may correlate with proinflammatory Stat3 signaling activities and IL-17 levels in breast cancer (BC) patients.', 'This study examined HPV infection by GenChip technology, constitutively active Stat3 (p-Stat3) and IL-17 levels by immunohistochemistry (IHC) using specific antibodies in 379 BC patients, together with 245 paired adjacent breast adenosis (ABA) tissues and 100 unrelated breast adenosis (BA) tissues.', \"We obtained four major findings: (1) HR-HPV16/18 infections existed in 10.5% (34/325) of BC issues, higher than control BA tissues (4%, 4/100, P = 0.047). (2) Using IHC methodology, BC tissues showed more overactive p-Stat3 (2+/3+, 38.5%, 146/379) than ABA tissues (27.3%, 67/245, P < 0.001); similarly, BC also had more tissues overexpressing IL-17 (2+/3+, 61.5%, 233/379) than ABA tissues (51.8%, 127/245, P < 0.001). (3) High levels (2+/3+) of both active p-Stat3 and IL-17 correlated with poor differentiation and lymph nodal metastasis in BC (both with P < 0.05), but not with patients' prognosis. (4) HR-HPV infections correlated with both active p-Stat3 (P = 0.018) and its downstream IL-17 levels (P = 0.021) in BC tissues.",
            "output": [
                "Does human papillomavirus infection correlate with inflammatory Stat3 signaling activity and IL-17 expression in patients with breast cancer?"
            ]
        },
        {
            "id": "task847-06fe6e1dc96f44c78ff99392d965df20",
            "input": "Bracing is a common treatment for patients with adolescent idiopathic scoliosis (AIS) and is recommended for most skeletally immature patients with a curve of 25-45\u00b0 in order to prevent or delay curve progression. The aim of this study was to determine at which body habitus orthotic management for AIS becomes less effective. We hypothesize that overweight children are more likely to fail brace treatment.', 'This was a retrospective cohort study involving consecutive patients with AIS treated with a thoracolumbosacral orthosis at a large pediatric tertiary care center. Patients were divided into three groups based on BMI: (1) high-BMI group (BMI >85th percentile); (2) low-BMI group (BMI <20th percentile); (3) mid-BMI group (BMI 20th-85th percentile). Successful orthotic treatment was defined as an increase in the primary curve of <5\u00b0, prevention of progression past 45\u00b0, and avoidance of surgery.', 'The study cohort comprised 182 patients with a mean age of 12.5\\xa0years at brace prescription and a mean follow-up of 2\\xa0years. Compared to the mid-BMI group, high- and low-BMI patients were significantly more likely to fail orthotic management. The association between high-BMI and orthotic failure disappeared when compliance and in-brace correction were taken into account, but the association between low-BMI and each poor outcome remained significant.",
            "output": [
                "'s it just the big kids : both high and low BMI impact bracing success for adolescent idiopathic scoliosis?"
            ]
        },
        {
            "id": "task847-8ef9151933804b5e84e1a07a1f0b302c",
            "input": "Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional underpinnings in 22q11DS remain unclear. We quantitatively investigate the cognitive processes and associated neuroanatomy of spatial working memory in people with 22q11DS compared to matched controls. We examine whether there are significant between-group differences in spatial working memory using task related fMRI, Voxel based morphometry and white matter fiber tractography.', 'Multimodal magnetic resonance imaging employing functional, diffusion and volumetric techniques were used to quantitatively assess the cognitive and neuroanatomical features of spatial working memory processes in 22q11DS. Twenty-six participants with genetically confirmed 22q11DS aged between 9 and 52 years and 26 controls aged between 8 and 46 years, matched for age, gender, and handedness were recruited.', 'People with 22q11DS have significant differences in spatial working memory functioning accompanied by a gray matter volume reduction in the right precuneus. Gray matter volume was significantly correlated with task performance scores in these areas. Tractography revealed extensive differences along fibers between task-related cortical activations with pronounced differences localized to interhemispheric commissural fibers within the parietal section of the corpus callosum.",
            "output": [
                "Does multimodal MRI reveal structural connectivity differences in 22q11 deletion syndrome related to impaired spatial working memory?"
            ]
        },
        {
            "id": "task847-7cf1a5ac089e449695e31d4f71d59611",
            "input": "The ability of Yersinia pestis to form a biofilm is an important characteristic in flea transmission of this pathogen. Y. pestis laterally acquired two plasmids (pPCP1and pMT1) and the ability to form biofilms when it evolved from Yersinia pseudotuberculosis. Small regulatory RNAs (sRNAs) are thought to play a crucial role in the processes of biofilm formation and pathogenesis.', 'A pPCP1-derived sRNA HmsA (also known as sR084) was found to contribute to the enhanced biofilm formation phenotype of Y. pestis. The concentration of c-di-GMP was significantly reduced upon deletion of the hmsA gene in Y. pestis. The abundance of mRNA transcripts determining exopolysaccharide production, crucial for biofilm formation, was measured by primer extension, RT-PCR and lacZ transcriptional fusion assays in the wild-type and hmsA mutant strains. HmsA positively regulated biofilm synthesis-associated genes (hmsHFRS, hmsT and hmsCDE), but had no regulatory effect on the biofilm degradation-associated gene hmsP. Interestingly, the recently identified biofilm activator sRNA, HmsB, was rapidly degraded in the hmsA deletion mutant. Two genes (rovM and rovA) functioning as biofilm regulators were also found to be regulated by HmsA, whose regulatory effects were consistent with the HmsA-mediated biofilm phenotype.",
            "output": [
                "Does plasmid pPCP1-derived sRNA HmsA promote biofilm formation of Yersinia pestis?"
            ]
        },
        {
            "id": "task847-12888ab8708b4c568feade363ad5a9cb",
            "input": "Early full enteral feeding in preterm infants decreases morbidity and mortality. Our systematic review covered the effectiveness of rectal stimulation, suppositories and enemas on stooling patterns and feeding tolerance in low-birthweight infants born at up to 32 weeks. It comprised seven studies published between 2007 and 2014 and covered 495 infants.",
            "output": [
                "Are enemas , suppositories and rectal stimulation effective in accelerating enteral feeding or meconium evacuation in low-birthweight infants : a systematic review?"
            ]
        },
        {
            "id": "task847-24e03211e6a4405d9d0373050d9a4fcc",
            "input": "HIV patients exposed to abacavir have an increased risk of myocardial infarction, with contradictory results in the literature. The aim of our study was to determine whether abacavir has a direct effect on platelet activation and aggregation using platelets from healthy donors and from HIV-infected patients under therapy with an undetectable viral load.', 'Platelet-rich plasma (PRP) or whole blood from healthy donors was treated with abacavir (5 or 10 \u03bcg/mL) or its active metabolite carbovir diphosphate. Experiments were also performed using blood of HIV-infected patients (n\\u200a=\\u200a10) with an undetectable viral load. Platelet aggregation was performed on PRP by turbidimetry and under high shear conditions at 4000 s', 'Abacavir and carbovir diphosphate significantly increased the aggregation of platelets from healthy donors induced by collagen at 2 \u03bcg/mL (P\\u200a=\\u200a0.002), but not at 0.5 \u03bcg/mL. No effect of abacavir or carbovir diphosphate was observed on platelet aggregation induced by other physiological agonists or by high shear stress, or on thrombin generation. Pretreatment of blood from HIV-infected patients with abacavir produced similar results.",
            "output": [
                "Does abacavir have no prothrombotic effect on platelets in vitro?"
            ]
        },
        {
            "id": "task847-f4592a1efe504b24bcaa377467131382",
            "input": "Populations of Atlantic salmon display highly significant genetic differences with unresolved molecular basis. These differences may result from separate postglacial colonization patterns, diversifying natural selection and adaptation, or a combination. Adaptation could be influenced or even facilitated by the recent whole genome duplication in the salmonid lineage which resulted in a partly tetraploid species with duplicated genes and regions.', 'In order to elucidate the genes and genomic regions underlying the genetic differences, we conducted a genome wide association study using whole genome resequencing data from eight populations from Northern and Southern Norway. From a total of ~4.5 million sequencing-derived SNPs, more than 10\\xa0% showed significant differentiation between populations from these two regions and ten selective sweeps on chromosomes 5, 10, 11, 13-15, 21, 24 and 25 were identified. These comprised 59 genes, of which 15 had one or more differentiated missense mutation. Our analysis showed that most sweeps have paralogous regions in the partially tetraploid genome, each lacking the high number of significant SNPs found in the sweeps. The most significant sweep was found on Chr 25 and carried several missense mutations in the antiviral mx genes, suggesting that these populations have experienced differing viral pressures. Interestingly the second most significant sweep, found on Chr 5, contains two genes involved in the NF-KB pathway (nkap and nkrf), which is also a known pathogen target that controls a large number of processes in animals.",
            "output": [
                "Do atlantic salmon populations reveal adaptive divergence of immune related genes - a duplicated genome under selection?"
            ]
        },
        {
            "id": "task847-18de995e7e084435b50a8e7b4e35381c",
            "input": "Lung contusion is a major risk factor for the development of acute respiratory distress syndrome. We set to determine the role of toll-like receptor 3 and the binding of double-stranded RNA in the pathogenesis of sterile injury following lung contusion.', 'Toll-like receptor 3 expression was analyzed in postmortem lung samples from patients with lung contusion. Unilateral lung contusion was induced in toll-like receptor 3 (-/-), TIR-domain-containing adapter-inducing interferon-\u03b2 (-/-), and wild-type mice. Subsequently, lung injury and inflammation were evaluated. Apoptotic indices, phagocytic activity, and phenotypic characterization of the macrophages were determined. Double-stranded RNA in bronchoalveolar lavage and serum samples following lung contusion was measured. A toll-like receptor 3/double-stranded RNA ligand inhibitor was injected into wild-type mice prior to lung contusion.', 'Toll-like receptor 3 expression was higher in patients and wild-type mice with lung contusion. The degree of lung injury, inflammation, and macrophage apoptosis was reduced in toll-like receptor 3 (-/-), TIR-domain-containing adapter-inducing interferon-\u03b2 (-/-), and wild-type mice with toll-like receptor 3 antibody neutralization. Alveolar macrophages from toll-like receptor 3 (-/-) mice had a lower early apoptotic index, a predominant M2 phenotype and increased surface translocation of toll-like receptor 3 from the endosome to the surface. When compared with viral activation pathways, lung injury in lung contusion demonstrated increased p38 mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2 phosphorylation with inflammasome activation without a corresponding increase in nuclear factor-\u03baB or type-1 interferon production. Additionally, pretreatment with toll-like receptor 3/double-stranded RNA ligand inhibitor led to a reduction in injury, inflammation, and macrophage apoptosis.",
            "output": [
                "Does double-Stranded RNA interact With Toll-Like Receptor 3 in Driving the Acute Inflammatory Response Following Lung Contusion?"
            ]
        },
        {
            "id": "task847-9a7f64b2283e46dc96fa37ae63515239",
            "input": "Statins have been proposed as a potential treatment for systemic lupus erythematosus (SLE) due to their immunomodulatory properties, their role restoring endothelial function and preventing atherosclerosis. We evaluate the effect of a short period treatment with a low dose of atorvastatin and its withdrawal on early stage subclinical atherosclerosis.', 'Thirty-seven SLE females received 20\\u2009mg/day atorvastatin during eight weeks. At baseline, at the end of treatment and six months after atorvastatin withdrawal, disease activity, subclinical atherosclerosis -assessed by measuring carotid-femoral pulse wave velocity (PWV) - and quantification of circulating endothelial progenitor cells (EPC) - as a surrogate biological marker of subclinical atherosclerosis - were carried out.', 'The group of SLE patients with baseline pathological arterial stiffness showed a significant decrease of PWV after atorvastatin therapy (8.43\\u2009\u00b1\\u20091.45\\u2009m/s vs 7.42\\u2009\u00b1\\u20091.06\\u2009m/s; p\\u2009=\\u20090.002) that is maintained six months after treatment finished. Only patients of the middle-aged group showed a nearly significant decrease in the PWV measured along the study (7.16\\u2009\u00b1\\u20091.23\\u2009m/s vs 6.76\\u2009\u00b1\\u20090.82\\u2009m/s; p\\u2009=\\u20090.05). Atorvastatin induced a significant decrease in the circulating EPC percentage (0.65\\u2009\u00b1\\u20090.67 vs 0.40\\u2009\u00b1\\u20090.31; p\\u2009=\\u20090.023) as well as a downward trend of disease activity that it is observed by a decrease in SLE disease activity index simultaneously with an increase in C3 complement and significant decrease in serum concentration of vascular endothelial grow factor (VEGF) and sVCAM-1.",
            "output": [
                "Does short-term atorvastatin therapy improve arterial stiffness of middle-aged systemic lupus erythematosus patients with pathological pulse wave velocity?"
            ]
        },
        {
            "id": "task847-7bbfd59c08d740698b5daed878f6666b",
            "input": "Nitric oxide (NO) is produced by sinonasal epithelial cells as part of the innate immune response against bacteria. We previously described bitter-taste-receptor-dependent and -independent NO responses to product(s) secreted by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. We hypothesized that sinonasal epithelium would be able to detect the gram-positive, coagulase-negative bacteria Staphylococcus epidermidis and mount a similar NO response.', 'Sinonasal air-liquid interface cultures were treated with conditioned medium (CM) from lab strains and clinical isolates of coagulase-negative staphylococci and S aureus. NO production was quantified by fluorescence imaging. Bitter taste receptor signaling inhibitors were utilized to characterize the pathway responsible for NO production in response to S epidermidis CM.', 'S epidermidis CM contains a low-molecular-weight, heat, and protease-stabile product that induces an NO synthase (NOS)-mediated NO production that is less robust than the response triggered by S aureus CM. The S epidermidis CM-stimulated NO response is not inhibited by antagonists of phospholipase C isoform \u03b2-2 nor the transient receptor potential melastatin isoform 5 ion channel, both critical to bitter taste signaling.",
            "output": [
                "Does human upper airway epithelium produce nitric oxide in response to Staphylococcus epidermidis?"
            ]
        },
        {
            "id": "task847-25cad1bf49dd4a2282c96cf6dcb63ce1",
            "input": "Genomic selection (GS) is a promising approach for decreasing breeding cycle length in forest trees. Assessment of progeny performance and of the prediction accuracy of GS models over generations is therefore a key issue.', 'A reference population of maritime pine (Pinus pinaster) with an estimated effective inbreeding population size (status number) of 25 was first selected with simulated data. This reference population (n\\u2009=\\u2009818) covered three generations (G0, G1 and G2) and was genotyped with 4436 single-nucleotide polymorphism (SNP) markers. We evaluated the effects on prediction accuracy of both the relatedness between the calibration and validation sets and validation on the basis of progeny performance. Pedigree-based (best linear unbiased prediction, ABLUP) and marker-based (genomic BLUP and Bayesian LASSO) models were used to predict breeding values for three different traits: circumference, height and stem straightness. On average, the ABLUP model outperformed genomic prediction models, with a maximum difference in prediction accuracies of 0.12, depending on the trait and the validation method. A mean difference in prediction accuracy of 0.17 was found between validation methods differing in terms of relatedness. Including the progenitors in the calibration set reduced this difference in prediction accuracy to 0.03. When only genotypes from the G0 and G1 generations were used in the calibration set and genotypes from G2 were used in the validation set (progeny validation), prediction accuracies ranged from 0.70 to 0.85.",
            "output": [
                "Do performance of genomic prediction within and across generations in maritime pine?"
            ]
        },
        {
            "id": "task847-6201637e013c4e2381124bd93fe35a3c",
            "input": "To test the hypothesis that core and suggestive features in possible dementia with Lewy bodies (DLB) would vary in their ability to predict an abnormal dopamine transporter scan and therefore a follow-up diagnosis of probable DLB. A further objective was to assess the evolution of core and suggestive features in patients with possible DLB over time depending on the (123)I-FP-CIT SPECT scan result.', 'A total of 187 patients with possible DLB (dementia plus one core or one suggestive feature) were randomized to have dopamine transporter imaging or to follow-up without scan. DLB features were compared at baseline and at 6-month follow-up according to imaging results and follow-up diagnosis.', \"For the whole cohort, the baseline frequency of parkinsonism was 30%, fluctuations 29%, visual hallucinations 24%, and REM sleep behavior disorder 17%. Clinician-rated presence of parkinsonism at baseline was significantly (p = 0.001) more frequent and Unified Parkinson's Disease Rating Scale (UPDRS) score at baseline was significantly higher (p = 0.02) in patients with abnormal imaging. There was a significant increase in UPDRS score in the abnormal scan group over time (p < 0.01). There was relatively little evolution of the rest of the DLB features regardless of the imaging result.",
            "output": [
                "Do evolution of clinical features in possible DLB depending on FP-CIT SPECT result?"
            ]
        },
        {
            "id": "task847-b14462e1e58e494caac10f30424bef41",
            "input": "A recent meta-analysis showed that obstructive sleep apnea (OSA) is associated with a higher prevalence of cancer and cancer-related mortality; however, little information is available on the association between OSA and colorectal neoplasia.', 'We identified consecutive patients who underwent overnight polysomnography (PSG) and subsequent colonoscopy. We compared the prevalence of colorectal neoplasia between patients with or without OSA according to the results of PSG. For each patient with OSA, 1 or 2 controls matched for age (\u00b15 years), sex, body mass index (BMI), and smoking who had undergone first-time screening colonoscopy were selected.', 'Of the 163 patients, 111 patients were diagnosed with OSA and 52 patients were within the normal range of the Apnea-Hypopnea Index. Of the 111 patients with OSA, 18 patients (16.2%) had advanced colorectal neoplasia, including 4 (3.6%) colorectal cancers. In the multivariate analyses, OSA was associated with an increased risk of advanced colorectal neoplasia after adjusting for factors including age and sex (mild: odds ratio\\xa0[OR], 14.09; 95% confidence interval [CI], 1.55-127.83; P\\xa0= .019; moderate or severe: OR, 14.12; 95% CI, 1.52-131.25; P\\xa0= .020). Our case-control study revealed that the odds of detecting advanced colorectal neoplasia among patients with OSA were approximately 3.03 times greater than in the controls matched for age, sex, BMI, and smoking (OR, 3.03; 95% CI, 1.44-6.34; P\\xa0= .002).",
            "output": [
                "Is obstructive sleep apnea associated with an increased risk of colorectal neoplasia?"
            ]
        },
        {
            "id": "task847-149b1953d46e4bdf8ff9a0be4da86670",
            "input": "Although the rule of 3 is recommended to minimize the risk of perforation when esophageal dilation is performed using bougie dilators, there are no data to validate its use. Our aim was to investigate the association between the rule of 3 and adverse events (AEs) in esophageal dilation.', 'A retrospective chart review in patients who underwent esophageal bougie or balloon dilation between December 1991 and February 2013 at a tertiary hospital was performed. Data collection included patient demographics, stricture and procedural characteristics, AEs, and follow-up. Univariate logistic regression models were used to assess the risk of AEs and perforations.', 'A total of 297 patients (median age, 63 years; 60% men) underwent 2216 esophageal bougie or balloon dilations. Major AEs occurred in 22 (1%) dilation sessions, including 11 (0.5%) perforations, 4 (0.2%) fistulas, 3\\xa0(0.1%) hospitalizations for pain management, 2 (0.09%) clinically significant hemorrhages, 1 (0.04%) fever, and 1 (0.04%) tracheoesophageal voice prosthesis leak. Mean duration of treatment was 43.2 months (standard deviation, 47.7 months). Most strictures were benign (n\\xa0= 275; 93%) and complex in nature (n\\xa0= 198; 67%). Non-adherence to the rule of 3 occurred in 190 (13%) dilations with bougie dilators. Non-adherence was not associated with a higher rate of major AEs (1/190, 0.5% vs 15/953, 1.6%; P\\xa0= .18) and perforations (0/190, 0% vs 7/952, 0.7%; P\\xa0= .18). Gender, complex strictures, location of the stricture, type of dilator, and additional interventions were also not associated with major AEs or perforations. However, malignant strictures were associated with an increased risk of major AEs (odds ratio, 3.5; 95% confidence interval, 1.1-12.0) and perforations (odds ratio, 8.3; 95% confidence interval, 2.2-31.9).",
            "output": [
                "Does non-adherence to the rule of 3 increase the risk of adverse events in esophageal dilation?"
            ]
        },
        {
            "id": "task847-be31239a74334921b9899779100da1e5",
            "input": "To evaluate manual lymphatic drainage (MLD) and active exercise effects on lymphatic alterations of the upper limb (UL), range of motion (ROM) of shoulder, and scar complications after breast cancer surgery.', 'Clinical trial.', 'Health care center.', 'Women (N=105) undergoing radical breast cancer surgery who were matched for staging, age, and body mass index.', 'Women (n=52) were submitted to MLD and 53 to active exercises for UL for 1 month and followed up.', 'Shoulder ROM, surgical wound inspection and palpation, UL circumference measurements, and lymphoscintigraphy were performed in preoperative and postoperative periods.', 'There was no significant difference between groups with regard to wound healing complications, ROM, and UL circumferences. After surgery, 25 (48.1%) of the MLD group and 19 (35.8%) of the active exercise group showed worsening in radiopharmaceutical uptake velocity, whereas 9 (17.3%) of the MLD group and 11 (20.8%) of the active exercise group showed improved velocity (P=.445). With regard to uptake intensity, 27 (51.9%) of the MLD group and 21 (39.6%) of the active exercise group showed worsening whereas 7 (13.5%) of the MLD group and 7 (13.2%) of the active exercise group showed some improvement (P=.391). The presence of collateral circulation was similar in both groups at both time points evaluated. The active exercise group had a significant increase in postoperative liver absorption (P=.005), and the MLD group had a significant increase in postoperative dermal backflow (P=.024).",
            "output": [
                "Do manual Lymphatic Drainage and Active Exercise Effects on Lymphatic Function Translate Into Morbidities in Women Who Underwent Breast Cancer Surgery?"
            ]
        },
        {
            "id": "task847-4829b4265a734a13b57e5259848f4159",
            "input": "Immunohistochemical 4 (IHC4) score plus Clinical Treatment Score (CTS) is an inexpensive tool predicting risk of distant recurrence in women with early breast cancer (EBC). IHC4 score is based on ER, PR, HER2 and Ki67 index. This study explores the role of the combined score (IHC4\\xa0+\\xa0CTS) in predicting risk of locoregional recurrence (LRR) in women with EBC who had breast conservation surgery (BCS) without adjuvant radiotherapy (study group). The secondary objective was to evaluate the clinicopathological differences between our study group and women who had adjuvant radiation following BCS (control group).', 'Patients were selected from the local database over a 13-year period. IHC testing was done where results were missing. Combined scores were calculated using the appropriate formulae.', 'Patients in the study group (81 patients) had favorable clinicopathological features compared to the control group (1406 patients). The Cox regression indicated a statistically significant association between the combined score and the risk of LRR (p\\xa0=\\xa00.03). The incidence of LRR was zero, 20% and 33.3% in the low, intermediate and high risk groups respectively (p\\xa0=\\xa00.007). Margin status was the only variable not included in the combined score. The Cox regression analysis demonstrated that the combined score (p\\xa0=\\xa00.02) and the ordinal measure of margins (p\\xa0=\\xa00.03) were significant independent predictors of LRR.",
            "output": [
                "Does iHC4 score plus clinical treatment score predict locoregional recurrence in early breast cancer?"
            ]
        },
        {
            "id": "task847-da8ead6d426c46a1a52204227feacccf",
            "input": "The evidence on the prognostic value of transthoracic echocardiography (TTE) in elderly, hemodynamically stable patients with Pulmonary Embolism (PE) is limited.', 'To evaluate the prevalence of common echocardiographic signs of right ventricular (RV) dysfunction and their prognostic impact in hemodynamically stable patients aged \u226565years with acute PE in a prospective multicenter cohort.', 'TTE was performed by cardiologists. We defined RV dysfunction as a RV/left ventricular ratio >0.9 or RV hypokinesis (primary definition) or the presence of \u22651 or \u22652 of 6 predefined echocardiographic signs (secondary definitions). Outcomes were overall mortality and mortality/non-fatal recurrent venous thromboembolism (VTE) at 30days, adjusting for the Pulmonary Embolism Severity Index risk score and highly sensitive troponin T values.', 'Of 400 patients, 36% had RV dysfunction based on our primary definition, and 81% (\u22651 sign) and 53% (\u22652 signs) based on our secondary definitions, respectively. Using our primary definition, there was no association between RV dysfunction and mortality (adjusted HR 0.90, 95% CI 0.31-2.58) and mortality/non-fatal VTE (adjusted HR 1.09, 95% CI 0.40-2.98). Similarly, there was no statistically significant association between the presence of \u22651 or \u22652 echocardiographic signs (secondary definitions) and clinical outcomes.",
            "output": [
                "Does echocardiography predict mortality in hemodynamically stable elderly patients with acute pulmonary embolism?"
            ]
        },
        {
            "id": "task847-e0fcee840c384f4fb0b66316fba69e4a",
            "input": "The aim of this study is to investigate the relationship between sleep duration and hypertension in a middle-aged Chinese population.', 'Cross-sectional data of 20,505 individuals aged 35-64\\xa0years from Taizhou longitudinal study was used. Logistic regression models were used to calculate odds ratios (ORs) for the risk of pre-hypertension and hypertension in association with sleep duration.', 'Short sleep duration was associated with high systolic and diastolic blood pressure in comparison with sleep duration of 7-8\\xa0h in females. Short sleep duration was also associated with an increased risk of hypertension in females. Age-stratified analysis showed that as compared with sleep duration of 7-8\\xa0h, sleep duration <6\\xa0h increased risk of hypertension after controlling for multiple covariates with an OR of 1.766 (1.024-2.775) in early middle-aged females of 35-44\\xa0years. More importantly, sleeping less than 6\\xa0h is associated with increased risk of pre-hypertension in females of this age category, after controlling for multiple covariates with an OR of 1.769 (1.058-2.958).",
            "output": [
                "Is short sleep duration associated with increased risk of pre-hypertension and hypertension in Chinese early middle-aged females?"
            ]
        },
        {
            "id": "task847-7bb6534634c24f48a1a543987dddfc9b",
            "input": "Butyrate has been shown to potently regulate energy expenditure and lipid metabolism in animals, yet the underlying mechanisms remain to be fully understood. The aim of this study was to investigate the molecular mechanisms of butyrate (in the form of butyrate glycerides, BG)-induced lipid metabolism at the level of gene expression in the jejunum and liver of broilers.', 'Two animal experiments were included in this study. In Experiment 1, two hundred and forty male broiler chickens were equally allocated into two groups: 1) basal diet (BD), 2) BG diets (BD + BG). Growth performance was compared between treatments for the 41-day trial. In Experiment 2, forty male broiler chickens were equally allocated into two groups. The general experimental design, group and management were the same as described in Experiment 1 except for reduced bird numbers and 21-day duration of the trial. Growth performance, abdominal fat deposition, serum lipid profiles as well as serum and tissue concentrations of key enzymes involved in lipid metabolism were compared between treatments. RNA-seq was employed to identify both differentially expressed genes (DEGs) and treatment specifically expressed genes (TSEGs). Functional clustering of DEGs and TSEGs and signaling pathways associated with lipid metabolism were identified using Ingenuity Pathways Analysis (IPA) and DAVID Bioinformatics Resources 6.7 (DAVID-BR). Quantitative PCR (qPCR) assays were subsequently conducted to further examine the expression of genes in the peroxisome proliferator-activated receptors (PPAR) signaling pathway identified by DAVID-BR. Dietary BG intervention significantly reduced abdominal fat ratio (abdominal fat weight/final body weight) in broilers. The decreased fat deposition in BG-fed chickens was in accordance with serum lipid profiles as well as the level of lipid metabolism-related enzymes in the serum, abdominal adipose, jejunum and liver. RNA-seq analysis indicated that dietary BG intervention induced 79 and 205 characterized DEGs in the jejunum and liver, respectively. In addition, 255 and 165 TSEGs were detected in the liver and jejunum of BG-fed group, while 162 and 211 TSEGs genes were observed in the liver and jejunum of BD-fed birds, respectively. Bioinformatic analysis with both IPA and DAVID-BR further revealed a significant enrichment of DEGs and TSEGs in the biological processes for reducing the synthesis, storage, transportation and secretion of lipids in the jejunum, while those in the liver were for enhancing the oxidation of ingested lipids and fatty acids. In particular, transcriptional regulators of THRSP and EGR-1 as well as several DEGs involved in the PPAR-\u03b1 signaling pathway were significantly induced by dietary BG intervention for lipid catabolism.",
            "output": [
                "Does transcriptome Analysis reveal Regulation of Gene Expression for Lipid Catabolism in Young Broilers by Butyrate Glycerides?"
            ]
        },
        {
            "id": "task847-200c1610deee4f64b7565990deb983da",
            "input": "Barrett esophagus (BE) is considered precursor condition of esophageal adenocarcinoma. Its incidence and prevalence are increasing in general population. Studies reported that metabolic syndrome (MS) or diabetes mellitus (DM) is related to increased risk of BE. Current study was to assess and better understand the relationship between MS /DM and BE.', \"Electronic search was conducted in the database Pubmed/Medline (-December, 2015), Embase (-December, 2015), Cochrane Library (-December, 2015), and Web of Knowledge (-December, 2015). Studies included were assessed with summary odds ratios (ORs) with 95% confidence intervals (CIs) and compared exposure group with control group. The heterogeneity was examined by the funnel plot and the Egger's test. Subgroup analyses and sensitive analyses were performed for the detection of possible heterogeneity and impact on stability of analysis results.\", \"Twelve publications met the criteria and included 355,311 subjects were analyzed. The pooled results showed MS was closely associated with increased risk of BE (OR\\u200a=\\u200a1.23; 95%CI 1.03-1.47; P\\u200a=\\u200a0.024), and yet DM did not significantly increase the risk of BE (OR\\u200a=\\u200a1.07; 95%CI 0.82-1.38; P\\u200a=\\u200a0.627). Substantial heterogeneities were detected. No significant publication bias was detected by Egger's test (P\\u200a=\\u200a0.23).",
            "output": [
                "Is metabolic syndrome associated with increased risk of Barrett esophagus : A meta-analysis?"
            ]
        },
        {
            "id": "task847-6aa74fd3e1b7462f850bd477534ca041",
            "input": "Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients.', 'We analysed 678 patients with cirrhosis. Sarcopenia, sarcopenic obesity and myosteatosis were analysed by CT scan using the third lumbar vertebrae skeletal muscle and attenuation indexes, using previously validated gender-and body mass index-specific cutoffs.', 'Patients were predominately men (n\\u2009=\\u2009457, 67%), and cirrhosis aetiology was hepatitis C virus in 269 patients (40%), alcohol in 153 (23%), non-alcoholic steatohepatitis/cryptogenic in 96 (14%), autoimmune liver disease in 55 (8%), hepatitis B virus in 43 (6%), and others in 5 patients (1%). Sarcopenia was present in 292 (43%), 135 had sarcopenic obesity (20%) and 353 had myosteatosis (52%). Patients with sarcopenia (22\\u2009\u00b1\\u20093 vs. 95\\u2009\u00b1\\u200922\\u2009months, P\\u2009<\\u20090.001), sarcopenic obesity (22\\u2009\u00b1\\u20093 vs. 95\\u2009\u00b1\\u200922\\u2009months, P\\u2009<\\u20090.001), and myosteatosis (28\\u2009\u00b1\\u20095 vs. 95\\u2009\u00b1\\u200922\\u2009months, P\\u2009<\\u20090.001) had worse median survival than patients without muscular abnormalities. By multivariate Cox regression analysis, both sarcopenia [hazard ratio (HR) 2.00, 95% confidence interval (CI) 1.44-2.77, P\\u2009<\\u20090.001], and myosteatosis (HR 1.42, 95% CI 1.02-1.07, P\\u2009=\\u20090.04) were associated with mortality.",
            "output": [
                "Are sarcopenic obesity and myosteatosis associated with higher mortality in patients with cirrhosis?"
            ]
        },
        {
            "id": "task847-123076162f084e129257815bcdc21c20",
            "input": "Improving quality of life (QoL) is an important objective in the treatment of schizophrenia. The aim of the current study was to examine to what extent resilience, self-esteem, hopelessness, and psychopathology are correlated with QoL.', 'We recruited 52 out-patients diagnosed with schizophrenia according to DSM-IV criteria and 77 healthy control subjects from the general community. In patients, psychopathology was quantified by the Positive and Negative Syndrome Scale. The following scales were used in both patients and control subjects: the Berliner Lebensqualit\u00e4tsprofil, the Resilience Scale, the Rosenberg Self-Esteem Scale, and the Beck Hopelessness Scale to assess QoL, resilience, self-esteem, and hopelessness respectively.', 'Patients with schizophrenia presented with significantly less QoL, resilience, self-esteem, and hope compared to healthy control subjects. In patients, QoL correlated moderately with resilience, self-esteem, and hopelessness and weakly with symptoms. With respect to the latter, particularly depression and positive symptoms were negatively correlated with QoL.",
            "output": [
                "Is quality of life in stabilized patients with schizophrenia mainly associated with resilience and self-esteem?"
            ]
        },
        {
            "id": "task847-6c00a2b2af1240a0b5da82c6050b56d1",
            "input": "Many species belonging to the genus Colletotrichum cause anthracnose disease on a wide range of plant species. In addition to their economic impact, the genus Colletotrichum is a useful model for the study of the evolution of host specificity, speciation and reproductive behaviors. Genome projects of Colletotrichum species have already opened a new era for studying the evolution of pathogenesis in fungi.', 'We sequenced and annotated the genomes of four strains in the Colletotrichum acutatum species complex (CAsc), a clade of broad host range pathogens within the genus. The four CAsc proteomes and secretomes along with those representing an additional 13 species (six Colletotrichum spp. and seven other Sordariomycetes) were classified into protein families using a variety of tools. Hierarchical clustering of gene family and functional domain assignments, and phylogenetic analyses revealed lineage specific losses of carbohydrate-active enzymes (CAZymes) and proteases encoding genes in Colletotrichum species that have narrow host range as well as duplications of these families in the CAsc. We also found a lineage specific expansion of necrosis and ethylene-inducing peptide 1 (Nep1)-like protein (NLPs) families within the CAsc.",
            "output": [
                "Are gene family expansions and contractions associated with host range in plant pathogens of the genus Colletotrichum?"
            ]
        },
        {
            "id": "task847-c34cf0c516984fd6a3ddcf2c1fe1947e",
            "input": "Impairments of intestinal barrier function are discussed as risk factors for the development and progression of non-alcoholic fatty liver disease (NAFLD). Studies suggest an association between arginine/citrulline homeostasis and the development of liver damages. Here, the effect of an oral L-citrulline (Cit) supplement on the development of a Western-style diet (WSD)-induced NAFLD was determined in mice.', 'Female 6- to 8-week-old C57BL/6J mice were either pair-fed a liquid Western-style or control diet (C)\\xa0\u00b1\\xa02.5\\xa0g/kg bodyweight Cit for 6\\xa0weeks (C\\xa0+\\xa0Cit or WSD\\xa0+\\xa0Cit). Indices of liver damage, glucose metabolism, intestinal barrier function and NO synthesis were measured.', 'While bodyweight gain was similar between groups, markers of glucose metabolism like fasting blood glucose and HOMA index and markers of liver damage like hepatic triglyceride levels, number of neutrophils and plasminogen activator inhibitor-1 protein levels were significantly lower in WSD\\xa0+\\xa0Cit-fed mice when compared to WSD-fed mice only. Protein levels of the tight junction proteins occludin and zonula occludens-1 in duodenum were significantly lower in mice fed a WSD when compared to those fed a WSD\\xa0+\\xa0Cit (-~70 and -~60\\xa0%, respectively, P\\xa0<\\xa00.05), whereas portal endotoxin levels, concentration of 3-nitrotyrosine protein adducts in duodenum and toll-like receptor-4 mRNA expression in livers of WSD\\xa0+\\xa0Cit-fed mice were markedly lower than in WSD-fed mice (-~43\\xa0%, P\\xa0=\\xa00.056; -~80 and -~48\\xa0%, respectively, P\\xa0<\\xa00.05).",
            "output": [
                "Does oral citrulline supplementation protect female mice from the development of non-alcoholic fatty liver disease ( NAFLD )?"
            ]
        },
        {
            "id": "task847-2b8c52d9bbd8489d9126ed2c93295fd0",
            "input": "Adolescents with type 1 diabetes are at increased risk for deteriorating glycemic control, poor quality of life, and depressive symptoms. Stress and coping are related to these outcomes in adolescents with diabetes, yet few studies have examined these constructs longitudinally.', 'This study aimed to describe stress and coping in adolescents with type 1 diabetes and to examine coping strategies as predictors of adolescent adjustment (i.e., depressive symptoms, quality of life) and glycemic control.', \"Adolescents with type 1 diabetes completed measures of diabetes-related stress, coping, symptoms of depression, and quality of life at baseline, 6\\xa0months, and 12\\xa0months. Data on glycemic control were collected from the adolescents' medical charts.\", \"The adolescents' use of primary control coping (e.g., problem solving) and secondary control engagement coping (e.g., positive thinking) strategies predicted significantly fewer problems with quality of life and fewer depressive symptoms over time. In contrast, the use of disengagement coping strategies (e.g., avoidance) predicted more problems with quality of life and depressive symptoms. Coping was not a significant predictor of glycemic control. Coping mediated the effects of diabetes-related stress on depressive symptoms and quality of life.",
            "output": [
                "Does stress and Coping predict Adjustment and Glycemic Control in Adolescents with Type 1 Diabetes?"
            ]
        },
        {
            "id": "task847-a70bdb7ac0b8489a982e711b6bc9b495",
            "input": "Apicomplexan parasites actively release transmembrane (TM) adhesive proteins involved in host cell attachment and invasion. Rhomboids, a family of intramembrane serine proteases, cleave these secreted adhesive proteins within their TM domains as an essential step in completing the invasion process. In Cryptosporidium parvum, the activity of rhomboids in cleaving microneme proteins (MICs) has not been reported. In the present study, the interaction between C. parvum rhomboids (CpROM1 and CpROM4) and C. parvum microneme proteins (CpGP900 and CpTRAP-C1) was investigated using yeast two-hybrid assay and co-immunoprecipitation assays.', 'Our study demonstrated that CpROM1 protein could interact with CpGP900 protein in co-transformed AH109 yeasts. Analysis of these proteins in co-transfected mammalian cells showed that the cleavage product of the CpGP900 protein was detected in the co-transfected cells. As control, CpGP900 only was transfected into cells and no cleavage was observed. The results suggested that CpGP900 protein was the substrate of CpROM1. Moreover, CpROM1 and CpROM4 could not cleave CpTRAP-C1 protein, which is the substrate of T. gondii rhomboid 2.",
            "output": [
                "Does cryptosporidium parvum rhomboid1 have an activity in microneme protein CpGP900 cleavage?"
            ]
        },
        {
            "id": "task847-3ad37fc295fb4c49be4c4cf261ddf993",
            "input": "The diagnostic criteria for active infectious syphilis in the clinic are important matter of controversy and debate. So far, clinicians habitually do use the negative results of the nontreponemal and/or the specific antitreponemal IgM as the evidences of disease-free or active infection-free status.', 'We present a case study involving a patient who was admitted to Zhongshan Hospital because of cerebral infarct. Clinical examination indicated he had a history of latent syphilis with negative nontreponemal and specific antitreponemal IgM tests. The cerebrospinal fluid sample from the patient was inoculated into seronegative New Zealand rabbit.', 'Motile Treponema pallidum was detected by a rabbit infectivity test in the patient\\'s cerebrospinal fluid. This syphilis strain was confirmed by DNA subtyping form of \"centers for disease control subtype/tp0548 sequence type\", and the strain type was 14d/f. Treatment with benzathine penicillin provided no apparent benefit, but treatment with aqueous crystalline penicillin G, especially recommended for neurosyphilis, led to disease regression. No evidence of cerebral infarct was observed during a 2-year follow-up period.",
            "output": [
                "Does a negative nontreponemal and/or specific antitreponemal IgM test exclude active infectious syphilis : evidence from a rabbit infectivity test : A case report?"
            ]
        },
        {
            "id": "task847-9c391bafa9244f5081fb7ef2b735b1e7",
            "input": "Intravenous tissue-type plasminogen activator (tPA) is a proven treatment for acute ischemic stroke, but there has been limited evaluation among patients aged \u226590 years.', 'We analyzed data from the Get With The Guidelines-Stroke national quality improvement registry from January 2009 to April 2013. Frequency, determinants, and outcomes of tPA use were compared among patients aged \u226590 and 3 younger age groups (18-64, 65-79, and 80-89 years).', 'Among 35\\u2009708 patients from 1178 sites who arrived within 2 hours of time last known well and received tPA, 2585 (7.2%) were \u226590 years. Compared with younger patients, the rate of tPA use among patients without a documented contraindication was lower among patients aged \u226590 years (67.4% versus 84.1% in 18-89-year olds; P<0.0001). Discharge outcomes among individuals aged \u226590 years included discharge to home or acute rehabilitation in 31.4%, independent ambulation at discharge in 13.4%, symptomatic hemorrhage in 6.1%, and in-hospital mortality or hospice discharge in 36.4%. On multivariable analysis, good functional outcomes generally occurred less often and mortality more often among patients aged \u226590 years. The risk of symptomatic hemorrhage was increased compared with patients <65 years but was not significantly different than the risk in 66- to 89-year olds.",
            "output": [
                "Do use and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients \u226590 Years of Age?"
            ]
        },
        {
            "id": "task847-4923a647000640729d6155ce615098f3",
            "input": "Only 2\\xa0% of the human genome code for proteins. Among the remaining 98\\xa0%, transposable elements (TEs) represent millions of sequences. TEs have an impact on genome evolution by promoting mutations. Especially, TEs possess their own regulatory sequences and can alter the expression pattern of neighboring genes. Since they can potentially be harmful, TE activity is regulated by epigenetic mechanisms. These mechanisms participate in the modulation of gene expression and can be associated with some human diseases resulting from gene expression deregulation. The fact that the TE silencing can be removed in cancer could explain a part of the changes in gene expression. Indeed, epigenetic modifications associated locally with TE sequences could impact neighboring genes since these modifications can spread to adjacent sequences.', 'We compared the histone enrichment, TE neighborhood, and expression divergence of human genes between a normal and a cancer conditions. We show that the presence of TEs near genes is associated with greater changes in histone enrichment and that differentially expressed genes harbor larger histone enrichment variation related to the presence of particular TEs.",
            "output": [
                "Is the transposable element environment of human genes associated with histone and expression changes in cancer?"
            ]
        },
        {
            "id": "task847-48db8959f6924f2b9413b2b9728a58e6",
            "input": "Lymph node ratio (LNR), positive nodes divided by nodes examined, has been proposed for prognostication in melanoma to mitigate problems with low node counts. However, it is unclear if LNR offers superior prognostication over total counts of positive nodes and nodes examined. Additionally, the prognostic value of LNR may change if a threshold number of nodes are examined. We evaluated whether LNR is more prognostic than positive nodes and nodes examined, and whether the prognostic value of LNR changes with minimum thresholds.', \"Using the National Cancer Data Base Participant User File, we identified 74,692 incident cases with nodal dissection during 2000-2006. We compared LNR versus counts of examined and positive nodes based on Harrell's C, a measure of predictive ability. We then stratified by total nodes examined: greater versus fewer than ten for axillary lymph node dissection (ALND) and greater versus fewer than five for inguinal lymph node dissection (ILND).\", \"Overall, LNR had a Harrell's C of 0.628 (95\\xa0% confidence interval [CI] 0.625-0.631). Examined and positive nodes were not significantly different from this, with a Harrell's C of 0.625 (95\\xa0% CI 0.621-0.630). In ALND, LNR had a Harrell's C of 0.626 (95\\xa0% CI 0.610-0.643) with \u226510 nodes versus 0.554 (95\\xa0% CI 0.551-0.558)\\xa0<\\xa010 nodes. In ILND, LNR had a Harrell's C of 0.679 (95\\xa0% CI 0.664-0.694) with \u22655 nodes versus C of 0.601 (95\\xa0% CI 0.595-0.606)\\xa0<\\xa05 nodes.",
            "output": [
                "Does lymph Node Ratio be Less Prognostic in Melanoma When Minimum Node Retrieval Thresholds Are Not Met?"
            ]
        },
        {
            "id": "task847-7de4c267cc2f4a49853a9fc8393ebce6",
            "input": "Obesity and its related co-morbidities such as non-alcoholic fatty liver disease (NAFLD) are increasing dramatically worldwide. The genetic variation in Patatin-like phospholipase domain-containing protein 3 (PNPLA3), which is also called adiponutrin (ADPN), in residue 148 (I148M, rs738409) has been associated with NAFLD. However, the regulation and function of PNPLA3 in metabolic diseases remains unclear. Laparoscopic gastric banding (LAGB) of severely obese patients reduces body weight, liver and adipose tissue inflammation. In this study, we investigated whether weight loss induced by LAGB affected PNPLA3 expression in hepatic and adipose tissue.', 'Liver and subcutaneous adipose tissue samples were collected from 28 severely obese patients before and 6\\xa0months after LAGB. PNPLA3 expression was assessed by quantitative real-time PCR. To understand whether inflammatory stimuli regulated PNPLA3 expression, we studied the effect of tumour necrosis factor alpha (TNF\u03b1) and lipopolysaccharide (LPS) on PNPLA3 expression in human adipocytes and hepatocytes.', 'PNPLA3 was strongly expressed in the liver and clearly detectable in subcutaneous adipose tissue of obese patients. Weight loss induced by LAGB of severely obese patients led to significantly increased adipose, but not hepatic, tissue expression of PNPLA3. Subcutaneous PNPLA3 expression negatively correlated with body-mass-index, fasting glucose and fasting insulin. TNF\u03b1 potently suppressed PNPLA3 expression in adipocytes but not hepatocytes.",
            "output": [
                "Does weight loss induced by bariatric surgery restore adipose tissue PNPLA3 expression?"
            ]
        },
        {
            "id": "task847-f5986dea7c264bd8bf8751d974cbd7cf",
            "input": "Hydrogen sulfide (H2S), produced by the activity of cystathionine-gamma-lyase (CSE), is a key mediator of inflammation in sepsis. The liver sinusoidal endothelial cells (LSECs) are important target and mediator of sepsis. The aim of this study was to investigate the role of CSE-derived H2S on inflammation and LSECs fenestrae in caecal-ligation and puncture (CLP)-induced sepsis using CSE KO mice.', 'Sepsis was induced by CLP, and mice (C57BL/6J, male) were sacrificed after 8 hours. Liver, lung, and blood were collected and processed to measure CSE expression, H2S synthesis, MPO activity, NF-\u03baB p65, ERK1/2, and cytokines/chemokines levels. Diameter, frequency, porosity and gap area of the liver sieve were calculated from scanning electron micrographs of the LSECs.', 'An increased CSE expression and H2S synthesizing activity in the liver and lung of wild-type mice following CLP-induced sepsis. This was associated with an increased liver and lung MPO activity, and increased liver and lung and plasma levels of the pro-inflammatory cytokines TNF-\u03b1, IL-6, and IL-1\u03b2, and the chemokines MCP-1 and MIP-2\u03b1. Conversely, CSE KO mice had less liver and lung injury and reduced inflammation following CLP-induced sepsis as evidenced by decreased levels of H2S synthesizing activity, MPO activity, and pro-inflammatory cytokines/chemokines production. Extracellular-regulated kinase (ERK1/2) and nuclear factor-\u03baB p65 (NF-\u03baB) became significantly activated after the CLP in WT mice but not in CSE KO mice. In addition, CLP-induced damage to the LSECs, as indicated by increased defenestration and gaps formation in the LSECs compared to WT sham control. CSE KO mice showed decreased defenestration and gaps formation following sepsis.",
            "output": [
                "Does cystathionine-Gamma-Lyase Gene Deletion protect Mice against Inflammation and Liver Sieve Injury following Polymicrobial Sepsis?"
            ]
        },
        {
            "id": "task847-61fe6884f3744614979ea74090722234",
            "input": "Inosine, a naturally occurring purine nucleoside, has been shown to stimulate axonal growth in cell culture and promote corticospinal tract axons to sprout collateral branches after stroke, spinal cord injury and TBI in rodent models.', 'To explore the effects of inosine on the recovery of motor function following cortical injury in the rhesus monkey.', 'After being trained on a test of fine motor function of the hand, monkeys received a lesion limited to the area of the hand representation in primary motor cortex. Beginning 24 hours after this injury and continuing daily thereafter, monkeys received orally administered inosine (500\\u200amg) or placebo. Retesting of motor function began on the 14th day after injury and continued for 12 weeks.', 'During the first 14 days after surgery, there was evidence of significant recovery within the inosine-treated group on measures of fine motor function of the hand, measures of hand strength and digit flexion. While there was no effect of treatment on the time to retrieve a reward, the treated monkeys returned to asymptotic levels of grasp performance significantly faster than the untreated monkeys. Additionally, the treated monkeys evidenced a greater degree of recovery in terms of maturity of grasp pattern.",
            "output": [
                "Does inosine enhance recovery of grasp following cortical injury to the primary motor cortex of the rhesus monkey?"
            ]
        },
        {
            "id": "task847-6d14b654ade94a7e9f4d3872b3898460",
            "input": "This study investigated the association between serum gamma-glutamyltransferase (GGT) level and subclinical atherosclerosis in patients with type 2 diabetes.', 'This cross-sectional study involved 1024 patients with type 2 diabetes mellitus. Measurement of brachial-ankle pulse wave velocity (baPWV; as a marker of arterial stiffness) and an ultrasound assessment of carotid atherosclerosis were performed. Subclinical atherosclerosis was defined by the presence of a high baPWV (\u22651720\\xa0cm/s), carotid atherosclerosis (intima-media thickness\\xa0>0.8\\xa0mm or the presence of plaques), and carotid stenosis (\u226550\\xa0% of luminal narrowing). The subjects were stratified into quartiles according to GGT level, and the relationship between GGT level and subclinical atherosclerosis was analysed.', 'Serum GGT levels were closely associated with obesity, atherogenic dyslipidemia, and metabolic syndrome. However, serum GGT levels did not show a linear association with baPWV, carotid intima-media thickness, or plaque grade. The prevalence of high baPWV, carotid atherosclerosis, and carotid stenosis did not differ between the quartiles in men and women. Multivariate logistic regression analyses revealed no association between GGT level and high baPWV, carotid atherosclerosis, and carotid stenosis, either as continuous variables or quartiles.",
            "output": [
                "Is serum gamma-glutamyltransferase associated with subclinical atherosclerosis in patients with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-076c38d946934a8a8e8d18bc76f8b8fd",
            "input": "The present study was undertaken to characterise the viral polypeptide 2 (VP2) gene of parvovirus from domestic cats in India.', 'The faecal samples from diarrhoeic/healthy domestic cats were collected from different geographical regions of India for screening by PCR assay followed by sequence analysis of the VP2 gene.', 'Canine parvovirus (CPV)/feline panleukopenia virus (FPV) infections were found in 12 samples (11.3%) of 106 faecal samples tested. Two new CPV-2a (297Ala and Asn426) and three FPV strains were identified by VP2 gene analysis. Several unique and existing amino acid mutations were found suggesting continuous evolution and emergence of newer variants. The phylogenetic analysis of the CPV sequences revealed that the two new CPV-2a strains from Mumbai (MC8) and Puducherry (P15) were clustered together in a single clade but had evolved independently and were ancestrally related to Chinese CPV-2a isolates. The FPV sequences (T-C-6 and T-C-1) from Thrissur, Kerala, formed a different clade (FPV clade) and were closely related to each other and had an ancestral relationship with an FPV isolate from the USA. Another FPV isolate from Goa (GC1) was positioned in the same clade but had evolved independently.",
            "output": [
                "Does molecular characterisation of parvoviruses from domestic cats reveal emergence of newer variants in India?"
            ]
        },
        {
            "id": "task847-9a347603cedb4c11bf2f4dcc29114822",
            "input": "Narcotic agents are frequently administered to manage increased intestinal motility in patients with short bowel syndrome, but long-term use is associated with gastrointestinal (GI) complaints. This analysis evaluated the incidence of narcotic use and abdominal adverse events among patients with short bowel syndrome receiving teduglutide.', 'Pooled data from patients who received \u22651 dose of teduglutide 0.05 mg/kg/d (n = 77) or placebo (n = 59) in either of 2 randomized, double-blind, phase III studies were analyzed.', 'Of 136 patients, 52 (38%) received narcotics. GI adverse events occurred more often among patients who received narcotics than among those who did not (abdominal pain, 51% vs 21%; nausea, 42% vs 11%; abdominal distension, 17% vs 8%; vomiting, 19% vs 6%). Logistic regression analysis indicated that the probability of GI adverse events was significantly increased in patients with narcotic use (P = .0009). In contrast, teduglutide treatment, as well as the interaction between teduglutide and narcotic use, did not affect the probability of GI adverse events.",
            "output": [
                "Do patients With Short Bowel on Narcotics During 2 Randomized Trials Have Abdominal Complaints Independent of Teduglutide?"
            ]
        },
        {
            "id": "task847-02ea37ac1fed4eeeb25f05801dbe58d0",
            "input": "Acute Kidney Injury (AKI) is a serious early complications in patients with acute pancreatitis (AP) that signifcantly increases mortality rates compared to patients without AKI. The early diagnosis of AKI during its treatable phases and implementation of appropriate treatment protocols can improve outcomes for this group of patients. A promising biomarker for AKI is neutrophil gelatinase-associated lipocalin (NGAL).', 'This study evaluated the diagnostic value of NGAL concentrations in serum and in urine for patients developing AKI as an early complication of AP compared to AP patients without AKI.', 'The study group composed of 65 patients (34 men and 31 women) with a mean age of 62.2 \u00b1 16 years with AP and hospitalized in the Surgery Department of the Direct Hospital in Sucha Beskidzka, Poland between January and December 2014. Serum NGAL (sNGAL) levels were measured with the BioVendor ELISA kit, and urine NGAL (uNGAL) with the Abbott ARCHITECT Analyzer.', 'In the early phase of AP, 11 patients (17%) developed AKI, including 10 patients with stage 1 and one with stage 2. AKI was associated with more severe AP, higher BISAP scores, the need for more intensive treatment, longer hospital stays and higher mortality. Both serum and urine NGAL concentrations were signifcantly higher in patients with AKI throughout the study and signifcantly predicted AKI in simple and multiple logistic regression adjusted for age, sex and comorbidities. Serum and urine NGAL concentrations were signifcantly correlated with levels of serum urea, creatinine, urine albumin, and the maximum change in serum creatinine. Serum and urine NGAL levels also correlated positively with direct neutrophil counts and CRP concentrations throughout the study.",
            "output": [
                "Is urine NGAL useful in the clinical evaluation of renal function in the early course of acute pancreatitis?"
            ]
        },
        {
            "id": "task847-1e027c614a064112855240a4e740924f",
            "input": "Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme, respectively. Transfusion of packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of packed red blood cells that have been stored for prolonged intervals (SRBCs; stored for 35-40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs.', 'To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after 2 hours of hemorrhagic shock, mice that received SRBCs were given a coinfusion of haptoglobin, hemopexin, or albumin.', 'Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh packed red blood cells, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects.",
            "output": [
                "Does haptoglobin or Hemopexin Therapy prevent Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells?"
            ]
        },
        {
            "id": "task847-6a0704e99e954cc680a625c252397e8b",
            "input": "The use of doxorubicin, a potent chemotherapeutic agent, is limited by cardiotoxicity. We tested the hypothesis that decreased soluble guanylate cyclase (sGC) enzyme activity contributes to the development of doxorubicin-induced cardiotoxicity.', 'Doxorubicin administration (20\\u2009mg/kg, intraperitoneally [IP]) reduced cardiac sGC activity in wild-type (WT) mice. To investigate whether decreased sGC activity contributes to doxorubicin-induced cardiotoxicity, we studied mice with cardiomyocyte-specific deficiency of the sGC \u03b11-subunit (mice with cardiomyocyte-specific deletion of exon 6 of the sGC\u03b11 allele [sGC\u03b11",
            "output": [
                "Does decreased Soluble Guanylate Cyclase contribute to Cardiac Dysfunction Induced by Chronic Doxorubicin Treatment in Mice?"
            ]
        },
        {
            "id": "task847-f1feb0f2b73f4b398494c73aaeb31196",
            "input": "Lung sound analysis is useful for objectively evaluating airways even in children with asymptomatic asthma. However, the relationship between lung sounds and morphological changes in the airways has not been elucidated. We examined the relationship between lung sounds and chronic morphological changes in the airways during the progression of asthma from onset in guinea pigs.', 'Eleven male guinea pigs were examined; of these, seven were used as asthma models and four as controls. The asthma models were sensitized and repeatedly challenged by inhaling albumin chicken egg. We measured lung sounds and lung function twice a week for 21 weeks. After the final antigen challenge, the lungs were excised for histological examination. We measured the ratio of airway wall thickness to the total airway area and the ratio of the internal area to the total airway area in the trachea, third bronchi, and terminal bronchioles.', 'Among the lungs sounds, the difference between the two groups was greatest with respect to inspiratory sound intensity. The ratio of airway wall thickness to the total airway area of the terminal bronchioles was greater in the asthma models than in the controls, and it correlated best with the changes in inspiratory sound intensity in the 501-1000-Hz range (r\\xa0=\\xa00.76, p\\xa0<\\xa00.003).",
            "output": [
                "Does changes in lung sound during asthma progression in a guinea pig model?"
            ]
        },
        {
            "id": "task847-2a4d19bcecb24f0cb9b9f6a720275ead",
            "input": "Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line.', 'To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry.', 'Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1.",
            "output": [
                "Does the Urtica dioica extract enhance sensitivity of paclitaxel drug to MDA-MB-468 breast cancer cells?"
            ]
        },
        {
            "id": "task847-ff54dc4e2a6244899ade32df99e4282a",
            "input": "MicroRNA-622 has been proven down-regulated in many human malignancies and correlated with tumor progression. However, its role in esophageal squamous cell carcinoma (ESCC) is still unclear. The aim of this study was to explore the expression and function of miR-622 in ESCC.', 'Using quantitative RT-PCR, we detected miR-622 expression in ESCC cell lines and primary tumor tissues. The association of miR-622 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-622 on the biological behavior of ESCC cells were investigated. At last, the potential regulatory function of miR-622 on E2F1 expression was confirmed.', 'miR-622 was found to be down-regulated in ESCC tissues and cell lines. Decreased miR-622 expression was closely correlated with aggressive clinicopathological features and poor overall survival. Multivariate regression analysis corroborated that low level of miR-622 expression was an independent unfavourable prognostic factor for patients with ESCC. Up-regulation of miR-622 could significantly reduce ESCC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while down-regulation of miR-622 showed opposite effects. Further, E2F1 was confirmed as a direct target of miR-622 by using Luciferase Reporter Assay.",
            "output": [
                "Does miR-622 functions as a tumor suppressor and directly target E2F1 in human esophageal squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-21c239c781324db584b5fcb978147e9b",
            "input": "The aim of this study was to analyze the biochemical and histochemical effects of radiation therapy and protective melatonin administration on periodontal tissues in rats with experimental periodontitis.', 'Sixty male Sprague Dawley rats were divided into six groups, as follows: control; experimental periodontitis (Ped); radiotherapy administration (Rt); experimental periodontitis and exposure to irradiation (Ped-Rt); radiotherapy and protective melatonin administration (Rt-Mel); and periodontitis, radiation therapy and protective melatonin administration (Ped-Rt-Mel). The rats were killed at the end of the experimental procedure, and the oxidative stress level and periodontal destruction were compared among the groups.', \"The oxidative stress index and the levels of 8-hydroxy-2'-deoxyguanosine, malondialdehyde and C-terminal telopeptide of type I collagen were found to be significantly higher in the Ped-Rt group compared with the Ped group (p < 0.05), and the levels were lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). Alveolar bone destruction and attachment level were also significantly lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05).",
            "output": [
                "Does melatonin prevent radiation-induced oxidative stress and periodontal tissue breakdown in irradiated rats with experimental periodontitis?"
            ]
        },
        {
            "id": "task847-0fabc359fac14dfe9df9e57710e41fb2",
            "input": "Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, widely expressed in neuronal cells and involved in nociception and neurogenic inflammation. We showed recently that TRPA1 mediates cartilage degradation and joint pain in the MIA-model of osteoarthritis (OA) suggesting a hitherto unknown role for TRPA1 in OA. Therefore, we aimed to investigate whether TRPA1 is expressed and functional in human OA chondrocytes.', 'Expression of TRPA1 in primary human OA chondrocytes was assessed by qRT-PCR and Western blot. The functionality of the TRPA1 channel was assessed by Ca(2+)-influx measurements. Production of MMP-1, MMP-3, MMP-13, IL-6, and PGE2 subsequent to TRPA1 activation was measured by immunoassay.', 'We show here for the first time that TRPA1 is expressed in primary human OA chondrocytes and its expression is increased following stimulation with inflammatory factors IL-1\u03b2, IL-17, LPS, and resistin. Further, the TRPA1 channel was found to be functional, as stimulation with the TRPA1 agonist AITC caused an increase in Ca(2+) influx, which was attenuated by the TRPA1 antagonist HC-030031. Genetic depletion and pharmacological inhibition of TRPA1 downregulated the production of MMP-1, MMP-3, MMP-13, IL-6, and PGE2 in osteoarthritic chondrocytes and murine cartilage, respectively.",
            "output": [
                "Is transient receptor potential ankyrin 1 ( TRPA1 ) functionally expressed in primary human osteoarthritic chondrocytes?"
            ]
        },
        {
            "id": "task847-971a47c0cdc94983a6e00da19cd49b4b",
            "input": "Managing aggressive breast cancers with enhanced chromosomal instability (CIN) is a significant challenge in clinics. Previously, we described that a cell cycle-associated kinase called Tousled-like kinase 2 (TLK2) is frequently deregulated by genomic amplifications in aggressive estrogen receptor-positive (ER",
            "output": [
                "Does amplification of TLK2 induce Genomic Instability via Impairing the G2-M Checkpoint?"
            ]
        },
        {
            "id": "task847-a7bd3670c05d4bae8e09193d9e4b86c8",
            "input": "Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells.\", 'Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity.', \"We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo.",
            "output": [
                "Does a Blockade of IGF Signaling sensitize Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities?"
            ]
        },
        {
            "id": "task847-b9a6c0e0129e47ed9cc16742338c65cb",
            "input": "Transport across the blood-brain barrier (BBB) is an important mediator of beta-amyloid (A\u03b2) accumulation in the brain and a contributing factor in the pathogenesis of Alzheimer's disease (AD). One of the receptors responsible for the transport of A\u03b2 in the BBB is the low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is susceptible to proteolytic shedding at the cell surface, which prevents endocytic transport of ligands. Previously, we reported a strong inverse correlation between LRP1 shedding in the brain and A\u03b2 transit across the BBB. Several proteases contribute to the ectodomain shedding of LRP1 including the \u03b1-secretase, a desintegrin and metalloproteinase domain containing protein 10 (ADAM10).\", 'The role of ADAM10 in the shedding of LRP1 and A\u03b2 BBB clearance was assessed through pharmacological inhibition of ADAM10 in an in vitro model of the BBB and through the use of ADAM10 endothelial specific knock-out mice. In addition, an acute treatment paradigm with an ADAM10 inhibitor was also tested in an AD mouse model to assess the effect of ADAM10 inhibition on LRP1 shedding and A\u03b2brain accumulation.', 'In the current studies, inhibition of ADAM10 reduced LRP1 shedding in brain endothelial cultures and increased A\u03b242 transit across an in vitro model of the BBB. Similarly, transgenic ADAM10 endothelial knockout mice displayed lower LRP1 shedding in the brain and significantly enhanced A\u03b2 clearance across the BBB compared to wild-type animals. Acute treatment with the ADAM10-selective inhibitor GI254023X in an AD mouse model substantially reduced brain LRP1 shedding and increased A\u03b240 levels in the plasma, indicating enhanced A\u03b2 transit from the brain to the periphery. Furthermore, both soluble and insoluble A\u03b240 and A\u03b242 brain levels were decreased following GI254023X treatment, but these effects lacked statistical significance.",
            "output": [
                "Does inhibition of ADAM10 promote the clearance of A\u03b2 across the BBB by reducing LRP1 ectodomain shedding?"
            ]
        },
        {
            "id": "task847-1cde8e9b218849c78e993299fa9abe69",
            "input": "Cardiac mass and volumes are often elevated in athletes, but it is not known whether moderate physical activity is also associated with cardiac dilatation and hypertrophy in a healthy adult population.', 'In total, 1096 adults (54% female, median age 39 years) without cardiovascular disease or cardiomyopathy-associated genetic variants underwent cardiac magnetic resonance imaging to determine biventricular volumes and function. Physical activity was assessed using a validated activity questionnaire. The relationship between cardiac parameters and activity was assessed using multiple linear regression adjusting for age, sex, race, and systolic blood pressure. Logistic regression was performed to determine the effect of activity on the likelihood of subjects having cardiac dilatation or hypertrophy according to standard cardiac magnetic resonance normal ranges. Increasing physical activity was associated with greater left ventricular (LV) mass (\u03b2=0.23; P<0.0001) and elevated LV and right ventricular volumes (LV: \u03b2=0.26, P<0.0001; right ventricular: \u03b2=0.26, P<0.0001). Physical activity had a larger effect on cardiac parameters than systolic blood pressure (0.06\u2264\u03b2\u22640.21) and a similar effect to age (-0.20\u2264\u03b2\u2264-0.31). Increasing physical activity was a risk factor for meeting imaging criteria for LV hypertrophy (adjusted odds ratio 2.1; P<0.0001), LV dilatation (adjusted odds ratio 2.2; P<0.0001), and right ventricular dilatation (adjusted odds ratio 2.2; P<0.0001).",
            "output": [
                "Does moderate Physical Activity in Healthy Adults be Associated With Cardiac Remodeling?"
            ]
        },
        {
            "id": "task847-cf8503cf53974510897bf207291db62f",
            "input": "Cardiovascular magnetic resonance T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities.', 'We performed blinded cardiovascular magnetic resonance analyses of left ventricular T1 and extracellular volume (ECV) fraction in 327 individuals (65% women, aged 64\u00b112 years). Thirty-seven individuals had breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors who received either anthracycline-based (n=37) or nonanthracycline-based (n=17) chemotherapy 2.8\u00b11.3 years earlier were compared with 236 cancer-free participants. Multivariable analyses were performed to determine the association between T1/ECV measures and variables associated with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058\u00b17 ms) and post- (1040\u00b17 ms) receipt of anthracycline chemotherapy versus comparators (965\u00b13 ms; P<0.0001 for both). Age-adjusted ECV, a marker of myocardial fibrosis, was elevated in anthracycline-treated cancer participants (30.4\u00b10.7%) compared with either pretreatment cancer (27.8\u00b10.7%; P<0.01) or cancer-free comparators (26.9\u00b10.2%; P<0.0001). T1 and ECV of nonanthracycline survivors were no different than pretreatment survivors (P=0.17 and P=0.16, respectively). Native T1 and ECV remained elevated in cancer survivors after accounting for demographics (including age), myocardial fibrosis risk factors, and left ventricular ejection fraction or myocardial mass index (P<0.0001 for all).",
            "output": [
                "Do anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors?"
            ]
        },
        {
            "id": "task847-5b417c08f09247f5b95d116d31b9deec",
            "input": "It is controversial whether high salt intake is directly associated with cardiovascular (CV) events and how far this relation is independent of blood pressure (BP). As Portugal has higher salt consumption and higher mortality by stroke than other European countries, we examined whether salt intake could predict the development of stroke and CV events in a hypertensive population.', 'In a longitudinal retrospective study of a cohort of 608 adult treated hypertensive patients 54.1\u00b114.3 years of age, BMI 29.3\u00b18.3\\u2009kg/m, 56.3% women and 17.1% diabetics, we evaluate the long-term prognostic significance of urinary sodium (UNa) excretion measured in 24\\u2009h valid samples within the first 3 months after admission along with 24\\u2009h ambulatory blood pressure monitoring and pulse wave velocity [(PWV), complior)] measurements.', 'The mean follow-up duration was 7.2 years (0.5-11.1 years), during which 122 CV events occurred including 80 strokes and 36 coronary events. In 608 patients (group A=507 without events and group B=101 with events: 69 strokes, 26 coronary events, six others), the mean 24\\u2009h UNa was 208\u00b179\\u2009mmol/day, corresponding to a salt intake of 12.1\u00b14.6\\u2009g/day. Twenty-four hours UNa correlated positively with BMI, PWV and systolic blood pressure (SBP) particularly with night-time SBP. Group B versus A showed higher UNa (260+98 vs. 198+71\\u2009mmol/day, P<0.001) and higher PWV, BP office, 24\\u2009h, daytime and night-time SBP. Logistic regression analysis identified age, night-time SBP and 24\\u2009h UNa+ [HR=1.09 (95% CI, 1.06-1.12, P<0.001)] for each 10\\u2009mmol increase of UNa+ as the only independent predictors of CV events. UNa+ above the median (189\\u2009mmol sodium/day) predicted CV events with HR=2.99 (95% CI, 1.75-5.13, P<0.001) with worse CV event-free survival rates (log rank statistics of 17.44, P<0.001).",
            "output": [
                "Is high salt intake associated with a higher risk of cardiovascular events : a 7.2-year evaluation of a cohort of hypertensive patients?"
            ]
        },
        {
            "id": "task847-d5074237336c4a12af9d0044975f24e0",
            "input": "Prior work shows that palliative homecare services reduce the subsequent need for hospitalizations and emergency services; however, no study has investigated whether this association is present for emergency department visits of high acuity or whether it only applies to low-acuity emergency department visits.', 'To examine the association between palliative versus standard homecare nursing and the rate of high-acuity and low-acuity emergency department visits among cancer decedents during their last 6\\u2009months of life.', 'This is a retrospective cohort study of end-of-life homecare patients in Ontario, Canada, who had confirmed cancer cause of death from 2004 to 2009. A multivariable Poisson regression analysis was implemented to examine the association between the receipt of palliative homecare nursing (vs standard homecare nursing) and the rate of high- and low-acuity emergency department visits, separately.', 'There were 54,743 decedents who received homecare nursing in the last 6\\u2009months of life. The receipt of palliative homecare nursing decreased the rate of low-acuity emergency department visits (relative rate\\u2009=\\u20090.53, 95% confidence interval\\u2009=\\u20090.50-0.56) and was significantly associated with a larger decrease in the rate of high-acuity emergency department visits (relative rate\\u2009=\\u20090.37, 95% confidence interval\\u2009=\\u20090.35-0.38).",
            "output": [
                "Is palliative homecare associated with reduced high- and low-acuity emergency department visits at the end of life : A population-based cohort study of cancer decedents?"
            ]
        },
        {
            "id": "task847-b9f06b7fde3147d9a126d37049b5676c",
            "input": "To clarify the lowering effect of metabolic syndrome (MetS) on serum prostate-specific antigen (PSA) levels in a Chinese screened population.', 'A total of 45 540 ostensibly healthy men aged 55-69 years who underwent routine health check-ups at Beijing Shijitan Hospital between 2008 and 2015 were included in the study. All the men underwent detailed clinical evaluations. PSA mass density was calculated (serum PSA level \u00d7 plasma volume \u00f7 prostate volume) for simultaneously adjusting plasma volume and prostate volume. According to the modified National Cholesterol Education Programme-Adult Treatment Panel (NCEP-ATP) III criteria, patients were dichotomized by the presence of MetS, and differences in PSA density and PSA mass density were compared between groups. Linear regression analysis was used to evaluate the effect of MetS on serum PSA levels.', 'When larger prostate volume in men with MetS was adjusted for, both PSA density and PSA mass density in men with MetS were significantly lower than in men without MetS, and the estimated difference in mean serum PSA level between men with and without MetS was greater than that before adjusting for prostate volume. In the multivariate regression model, the presence of MetS was independently associated with an 11.3% decline in serum PSA levels compared with the absence of MetS. In addition, increasing number of positive MetS components was significantly and linearly associated with decline in serum PSA levels.",
            "output": [
                "Is actual lowering effect of metabolic syndrome on serum prostate-specific antigen levels partly concealed by enlarged prostate : results from a large-scale population-based study?"
            ]
        },
        {
            "id": "task847-24068bc76f364ae790d249cf4c5ec66f",
            "input": "Increasing evidence points to the inflammatory character of atherosclerosis and several parameters of inflammation have been proposed as cerebrovascular risk markers. The objective of the research was to examine the connection of serum inflammatory parameters and ultrasound (US) characteristics of the structure and size of carotid plaque. We assumed that the number of leukocytes (Le) was an indicator of carotid plaque instability and an increased risk of stroke.', 'Serum inflammatory parameters: erythrocyte sedimentation rate in the first (ESR I) and second hour (ESR II), the number of Le, high sensitivity C-reactive protein (hsCRP) and fibrinogen were measured by standard methods. All the subjects (n = 75) were divided into 3 groups (symptomatic, asymptomatic and control). US evaluation of extracranial carotid arteries was performed in a duplex system. Plaques were classified into categories according to stenosis percentage (\u2265 50%, < 50%) and pursuant to echomorphological characteristics (Gray-Weale classification). In the subjects with stroke an ischemic lesion was confirmed by computed tomography.', 'The average values of biochemical parameters in the symptomatic group were: ESR I 29.57 \u00b1 29.87 cm, ESR II 51.60 \u00b1 36.87 cm, the number of Le 10.10 \u00b1 3.20 x 10\u2079 U/L, hsCRP 8.15 \u00b1 5.50 mg/L and fibrinogen 4.03 \u00b1 0.70 g/L. The average values of all testing biochemical parameters in symptomatic patients were significantly higher than in the asymptomatic ones and the control group: for ESR I (p < 0.05) and ESR II (p < 0.05); for the number of Le (p < 0.001); for hsCRP (p < 0.001) and fibrinogen (p < 0.001). Category I of echomorphological characteristics in the symptomatic group was present in 66.7% of the cases and it was significantly higher than in the asymptomatic (40.0%; p < 0.05) and the control group (20.0%; p < 0.01). Univariate logistic regression analysis confirmed that all testing biochemical parameters are indicators of stroke risk. Multivariate logistic regression analysis confirmed a statistically significant correlation of the number of Le and stroke risk, while the increase in the value by a unit of measurement was associated with the growth of risk by 3.22 times (from 1.67 to 6.22).",
            "output": [
                "Does leucocyte count indicate carotid plaque instability in stroke patients?"
            ]
        },
        {
            "id": "task847-f2c8fa1704d04616b5f29b9cbf2f29b2",
            "input": "B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPR-A) receptor signalling inhibits cardiac sympathetic neurotransmission, although C-type natriuretic peptide (CNP) is the predominant neuropeptide of the nervous system with expression in the heart and vasculature. We hypothesized that CNP acts similarly to BNP, and that transgenic rats (TGRs) with neuron-specific overexpression of a dominant negative NPR-B receptor would develop heightened sympathetic drive.', 'Mean arterial pressure and heart rate (HR) were significantly (P\\u2009<\\u20090.05) elevated in freely moving TGRs (n\\u2009=\\u20099) compared with Sprague Dawley (SD) controls (n\\u2009=\\u200910). TGR had impaired left ventricular systolic function and spectral analysis of HR variability suggested a shift towards sympathoexcitation. Immunohistochemistry demonstrated co-staining of NPR-B with tyrosine hydroxylase in stellate ganglia neurons. In SD rats, CNP (250\\u2009nM, n\\u2009=\\u20098) significantly reduced the tachycardia during right stellate ganglion stimulation (1-7\\u2009Hz) in vitro whereas the response to bath-applied norepinephrine (NE, 1\\u2009\u03bcM, n\\u2009=\\u20096) remained intact. CNP (250\\u2009nM, n\\u2009=\\u20098) significantly reduced the release of ",
            "output": [
                "Does c-type natriuretic peptide and natriuretic peptide receptor B signalling inhibit cardiac sympathetic neurotransmission and autonomic function?"
            ]
        },
        {
            "id": "task847-3a04aadf0d484b00ae3c78b329cb8009",
            "input": "For the majority of congenital heart diseases (CHDs), the full complexity of the causative molecular network, which is driven by genetic, epigenetic, and environmental factors, is yet to be elucidated. Epigenetic alterations are suggested to play a pivotal role in modulating the phenotypic expression of CHDs and their clinical course during life. Candidate approaches implied that DNA methylation might have a developmental role in CHD and contributes to the long-term progress of non-structural cardiac diseases. The aim of the present study is to define the postnatal epigenome of two common cardiac malformations, representing epigenetic memory, and adaption to hemodynamic alterations, which are jointly relevant for the disease course.', 'We present the first analysis of genome-wide DNA methylation data obtained from myocardial biopsies of Tetralogy of Fallot (TOF) and ventricular septal defect patients. We defined stringent sets of differentially methylated regions between patients and controls, which are significantly enriched for genomic features like promoters, exons, and cardiac enhancers. For TOF, we linked DNA methylation with genome-wide expression data and found a significant overlap for hypermethylated promoters and down-regulated genes, and vice versa. We validated and replicated the methylation of selected CpGs and performed functional assays. We identified a hypermethylated novel developmental CpG island in the promoter of SCO2 and demonstrate its functional impact. Moreover, we discovered methylation changes co-localized with novel, differential splicing events among sarcomeric genes as well as transcription factor binding sites. Finally, we demonstrated the interaction of differentially methylated and expressed genes in TOF with mutated CHD genes in a molecular network.",
            "output": [
                "Does comparative DNA methylation and gene expression analysis identify novel genes for structural congenital heart diseases?"
            ]
        },
        {
            "id": "task847-322af8c1943d41faa2d9d9fceffdafcb",
            "input": "The striated muscle costamere, a multiprotein complex at the boundary between the sarcomere and the sarcolemma, plays an integral role in maintaining striated muscle structure and function. Multiple costamere-associated proteins, such as integrins and integrin-interacting proteins, have been identified and shown to play an increasingly important role in the pathogenesis of human cardiomyopathy. Kindlin-2 is an adaptor protein that binds to the integrin \u03b2 cytoplasmic tail to promote integrin activation. Genetic deficiency of Kindlin-2 results in embryonic lethality, and knockdown of the Kindlin-2 homolog in Caenorhabditis elegans and Danio rerio suggests that it has an essential role in integrin function and normal muscle structure and function. The precise role of Kindlin-2 in the mammalian cardiac myocyte remains to be determined.', 'The current studies were designed to investigate the role of Kindlin-2 in the mammalian heart. We generated a series of cardiac myocyte-specific Kindlin-2 knockout mice with excision of the Kindlin-2 gene in either developing or adult cardiac myocytes. We found that mice lacking Kindlin-2 in the early developing heart are embryonic lethal. We demonstrate that deletion of Kindlin-2 at late gestation or in adult cardiac myocytes resulted in heart failure and premature death, which were associated with enlargement of the heart and extensive fibrosis. In addition, integrin \u03b21D protein expression was significantly downregulated in the adult heart.",
            "output": [
                "Does postnatal Loss of Kindlin-2 lead to Progressive Heart Failure?"
            ]
        },
        {
            "id": "task847-ccd626cc17724d9a9d162510d1e94ae3",
            "input": "Substantial country differences in neurosurgical training throughout Europe have recently been described, ranging from subjective rating of training quality to objective working hours per week. The aim of this study was to analyse whether these differences translate into the results of the written and oral part of the European Board Examination in Neurological Surgery (EBE-NS).', 'Country-specific composite scores for satisfaction with quality of theoretical and practical training, as well as working hours per week, were obtained from an electronic survey distributed among European neurosurgical residents between June 2014 and March 2015. These were related to anonymous country-specific results of the EBE-NS between 2009 and 2016, using uni- and multivariate linear regression analysis.', 'A total of n\\u2009=\\u20091025 written and n\\u2009=\\u200963 oral examination results were included. There was a significant linear relationship between the country-specific EBE-NS result in the written part and the country-specific composite score for satisfaction with quality of theoretical training [adjusted regression coefficient (RC) -3.80, 95\\xa0% confidence interval (CI) -5.43-7\\u2009-2.17, p\\u2009<\\u20090.001], but not with practical training or working time. For the oral part, there was a linear relationship between the country-specific EBE-NS result and the country-specific composite score for satisfaction with quality of practical training (RC 9.47, 95\\xa0% CI 1.47-17.47, p\\u2009=\\u20090.021), however neither with satisfaction with quality of theoretical training nor with working time.",
            "output": [
                "Do residency program trainee-satisfaction correlate with results of the European board examination in neurosurgery?"
            ]
        },
        {
            "id": "task847-0ce096fb298c4661a9ffa34546c65b15",
            "input": "Current diagnostic tests for gastroesophageal reflux disease (GERD) do not consistently measure chronicity of reflux. Mucosal impedance (MI) is a minimally invasive measurement to assess esophageal conductivity changes due to GERD. We aimed to investigate MI pattern in patients with symptoms of extraesophageal reflux (EER) in a prospective longitudinal cohort study.', 'Patients with potential symptoms of EER undergoing esophagogastroduodenoscopy (EGD) with wireless pH monitoring were studied. Participants included those with erosive esophagitis (E+), normal EGD/abnormal pH (E-/pH+), and normal EGD/normal pH (E-/pH-). MI was measured from the site of injury in patients with E+, as well as at 2, 5, and 10 cm above the squamocolumnar junction (SCJ) in all participants.', 'Forty-one patients with symptoms of EER were studied. MI measurements at 2\\u2009cm above the SCJ were significantly (P\\u2009=\\u20090.04) different among the three groups, with MI lowest for E+ and greatest for E-/pH- patients. Although not statistically significant, there is a graded increase in median (interquartile range) MI axially along the esophagus at 5\\u2009cm (P\\u2009=\\u20090.20) and at 10\\u2009cm (P\\u2009=\\u20090.27) above the SCJ, with those with reflux (E+ and E-/pH+) having a lower MI than those without.",
            "output": [
                "Is esophageal Mucosal Impedance Pattern Distinct in Patients With Extraesophageal Reflux Symptoms and Pathologic Acid Reflux?"
            ]
        },
        {
            "id": "task847-82767fd9f5054cc383b00757b6f5ee07",
            "input": "The antileukemic drug asparaginase, a key component in the treatment of acute lymphoblastic leukemia, acts by depleting asparagine from the blood. However, little is known about its pharmacokinetics and mechanisms of therapy resistance are poorly understood. Here, we explored the in vivo biodistribution of radiolabeled asparaginase, using a combination of in vivo imaging and biochemical techniques, and provide evidence for tissue specific clearance mechanisms, which could reduce effectiveness of the drug at these specific sites.', 'In vivo localization of Indium-111-labeled E.coli asparaginase was carried out in C57Bl/6 mice by both microSPECT/CT and by ex vivo biodistribution studies. Mice were treated with liposomal clodronate to investigate the effect of macrophage depletion on tracer localization and drug clearance in vivo. Moreover, macrophage cell line models RAW264.7 and THP-1, as well as cathepsin B deficient mice, were used to identify the cellular and molecular components controlling asparaginase pharmacokinetics.', 'In vivo imaging and biodistribution studies showed a rapid accumulation of asparaginase in macrophage-rich tissues such as liver, spleen and in particular bone marrow. Clodronate-mediated depletion of phagocytic cells markedly prolonged the serum half-life of asparaginase in vivo and decreased drug uptake in target organs. Immunohistochemistry and in vitro binding assays confirmed the involvement of macrophage-like cells in the uptake of asparaginase. We identified the activity of the lysosomal protease cathepsin B in macrophages as a rate-limiting factor in degrading asparaginase both in vitro and in vivo.",
            "output": [
                "Does in vivo imaging of antileukemic drug asparaginase reveal a rapid macrophage mediated clearance from the bone marrow?"
            ]
        },
        {
            "id": "task847-566d1e567d1444cdbce8fe0386e8f21b",
            "input": "Enterococcus faecalis is a pathogenic gram-positive bacterium closely associated with apical periodontitis. Although sodium hypochlorite (NaOCl) has been used as a common endodontic irrigant to eradicate bacteria in the root canal, it has not been elucidated whether NaOCl attenuates the inflammatory response induced by the E. faecalis virulence factor lipoteichoic acid (EfLTA).', 'Structurally intact EfLTA purified from E. faecalis was treated with NaOCl at various concentrations and time periods. Murine macrophage cell line RAW 264.7\\xa0was treated with interferon gamma followed by treatment with intact or NaOCl-treated EfLTA to determine the inducibility of inflammatory mediators such as nitric oxide, interferon gamma-inducible protein 10, and macrophage inflammatory protein-1\u03b1. Reporter gene assays assessed by flow cytometry were used to examine the ability of intact or\\xa0NaOCl-treated EfLTA to activate Toll-like receptor 2\\xa0(TLR2), which is known to recognize EfLTA on host cells. Structural damage of EfLTA by NaOCl was examined using\\xa0silver staining and thin-layer chromatography.', 'NaOCl-treated EfLTA showed markedly less induction\\xa0of nitric oxide, interferon gamma-inducible protein 10, and macrophage inflammatory protein-1\u03b1 in RAW 264.7\\xa0cells compared with intact EfLTA. In contrast to intact EfLTA that potently stimulated TLR2 activation, NaOCl-treated EfLTA did not activate TLR2. Structural analysis showed that NaOCl damaged EfLTA structure by deacylation.",
            "output": [
                "Does sodium Hypochlorite inactivate Lipoteichoic Acid of Enterococcus faecalis by Deacylation?"
            ]
        },
        {
            "id": "task847-42f3534078614aada014d8dfe0240a2d",
            "input": "Substance use and crime/recidivism are irrevocably linked. We explore the nuances of this association by highlighting the prevalence, trends, and correlates of substance use dsorders in a large group of probationers/parolees.', 'We examined SUDs among probationers and parolees in the United States using data from the National Study on Drug Use and Health (NSDUH). Logistic regression models were computed to examine eight distinct outcomes: alcohol abuse, illicit drug abuse, marijuana/hashish abuse, comorbid alcohol and illicit drug abuse, alcohol dependence, illicit drug dependence, marijuana/hashish dependence, and comorbid alcohol and illicit drug dependence.', 'Probationers/parolees have high prevalence rates across all SUDs categories and these trends have been relatively constant. Prevalence rates for alcohol abuse and dependence are two to six times higher than for marijuana and other illicit drug abuse and dependence. Key correlates of substance abuse for probationers/parolees include: age, gender, race/ethnicity, education, income, risk propensity, crime/violence measures, and comorbid substance abuse. Similar correlates were found for substance dependence, in addition to employment and mental health treatment.",
            "output": [
                "Does trends and correlate of substance use disorders among probationers and parolees in the United States 2002-2014?"
            ]
        },
        {
            "id": "task847-3740b8a20119412d96f06f17a5e210ca",
            "input": "The relationship between post-exercise heart-rate recovery (HRR) and resting cardiac autonomic modulation is an incompletely explored issue.', 'To correlate HRR with resting supine and orthostatic autonomic status.', 'HRR at the 1st, 3th, and 5th min following maximal treadmill exercise were correlated with 5-min time-domain (CV, pNN50 and rMSSD) and frequency-domain (TP, LF, HF, LFn, HFn, and LF/HF ratio) indices of heart-rate variability (HRV) in both supine and standing positions in 31 healthy physically active non-athletes men. Statistical analysis employed non-parametric tests with two-tailed p\\xa0value set at 5\\xa0%.', 'Absolute HRR and \u0394\\xa0%HRR at each post-exercise time did not correlated with HRV in supine position, as well as at 1st min in standing position. At the 3rd min and 5th min, these measures negatively correlated with pNN50, rMSSD, TP, and HF indices, and only in the 5th min, they showed negative correlation with HFn and positive correlation with LF, LFn, and LF/HF ratio in the standing position. Coefficient of HRR (CHRR) at the 1st min negatively correlated with pNN50 and rMSSD and at 3rd and 5th min showed positive correlation with LFn and LF/HF ratio in supine position. With HRV indices in standing position CHRR from the 1st to 5th min showed the same respective negative and positive correlations as the other measures.",
            "output": [
                "Does post-exercise heart-rate recovery correlate to resting heart-rate variability in healthy men?"
            ]
        },
        {
            "id": "task847-8e842671bdb84fb0a09c8c89e40a3317",
            "input": "Nitric oxide (NO) is an important vascular signalling molecule. NO is synthesised endogenously by endothelial nitric oxide synthase (eNOS). An alternate pathway is exogenous dietary nitrate, which can be converted to nitrite and then stored or further converted to NO and used immediately. Atherosclerosis is associated with endothelial dysfunction and subsequent lesion formation. This is thought to arise due to a reduction in the bioavailability and/or bioactivity of endogenous NO.', 'To determine if dietary nitrate can protect against endothelial dysfunction and lesion formation in the ApoE', 'ApoE",
            "output": [
                "Does low dose dietary nitrate improve endothelial dysfunction and plaque stability in the?"
            ]
        },
        {
            "id": "task847-5ae7745fab084c049f047a77ad469c6b",
            "input": "Bacterium-to-host signalling during infection is a complex process involving proteins, lipids and other diffusible signals that manipulate host cell biology for pathogen survival. Bacteria also release membrane vesicles (MV) that can carry a cargo of effector molecules directly into host cells. Supported by recent publications, we hypothesised that these MVs also associate with RNA, which may be directly involved in the modulation of the host response to infection.', \"Using the uropathogenic Escherichia coli (UPEC) strain 536, we have isolated MVs and found they carry a range of RNA species. Density gradient centrifugation further fractionated and characterised the MV preparation and confirmed that the isolated RNA was associated with the highest particle and protein containing fractions. Using a new approach, RNA-sequencing of libraries derived from three different 'size' RNA populations (<50nt, 50-200nt and 200nt+) isolated from MVs has enabled us to now report the first example of a complete bacterial MV-RNA profile. These data show that MVs carry rRNA, tRNAs, other small RNAs as well as full-length protein coding mRNAs. Confocal microscopy visualised the delivery of lipid labelled MVs into cultured bladder epithelial cells and showed their RNA cargo labelled with 5-EU (5-ethynyl uridine), was transported into the host cell cytoplasm and nucleus. MV RNA uptake by the cells was confirmed by droplet digital RT-PCR of csrC. It was estimated that 1% of MV RNA cargo is delivered into cultured cells.",
            "output": [
                "Does uropathogenic Escherichia coli release Extracellular Vesicles That Are Associated with RNA?"
            ]
        },
        {
            "id": "task847-d79d2efe756e4584a025d315e2b58781",
            "input": "The age gap between participants in trials and patients who could benefit from the drugs studied has been widely documented across different clinical areas. Patients with dementia included in clinical research are systematically younger than those in the general population. We examined the age gap between participants in recent clinical trials testing interventions for Alzheimer's disease and epidemiological data.\", \"We systematically searched literature databases (MedLine, EMBASE, the Cochrane Library) and ClinicalTrials.gov from 2000 to July 2015 to retrieve clinical trials testing pharmacologic treatments for Alzheimer's disease, other than cholinesterase inhibitors and memantine. We included ongoing and completed phase II/III randomized clinical trials, irrespective of their publication status. From each study reporting the participants' ages, we extracted size of sample, mean age, and standard deviation, and estimated the proportions of participants in different age classes. The number of patients with Alzheimer's disease by age class in the USA population was used for comparison.\", \"We included 165 clinical trials testing almost 100 different compounds, which enrolled or planned to enroll about 74,300 participants. Seventy-nine of these trials, accounting for about 26,800 participants, reported the age of the participants. The weighted mean age was 73.6 years (standard deviation, 8.2). People younger than 80 years were highly represented in clinical trials (78 %), despite the fact that those aged 80 and older form the majority (72 %) of patients with Alzheimer's disease. Only 8 % of clinical trial participants were 85 years or older.",
            "output": [
                "Are older patients still under-represented in clinical trials of Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-1c7ab3aed4bc43d190ee9874ac69971a",
            "input": "Hearing aids are prescribed to alleviate loss of audibility. It has been reported that about 31% of hearing aid users reject their own hearing aid because of annoyance towards background noise. The reason for dissatisfaction can be located anywhere from the hearing aid microphone till the integrity of neurons along the auditory pathway.', 'To measure spectra from the output of hearing aid at the ear canal level and frequency following response recorded at the auditory brainstem from individuals with hearing impairment.', 'A total of sixty participants having moderate sensorineural hearing impairment with age range from 15 to 65 years were involved. Each participant was classified as either Good or Poor Hearing aid Performers based on acceptable noise level measure. Stimuli /da/ and /si/ were presented through loudspeaker at 65dB SPL. At the ear canal, the spectra were measured in the unaided and aided conditions. At auditory brainstem, frequency following response were recorded to the same stimuli from the participants.', 'Spectrum measured in each condition at ear canal was same in good hearing aid performers and poor hearing aid performers. At brainstem level, better F",
            "output": [
                "Does encoding of speech sound at auditory brainstem level in good and poor hearing aid performers?"
            ]
        },
        {
            "id": "task847-afa570db090442d8a3b6f96f32350848",
            "input": "To determine the association of statin use with oncological outcomes and risk of pathologic upgrading following radical prostatectomy.', 'Using a prospectively populated database of 3042 men who underwent open radical prostatectomy, patients were grouped according to reported statin use at the time of surgery. The primary outcome was time to biochemical recurrence. The secondary outcome was risk of pathologic upgrading among a subset of 1256 patients with Gleason pattern 3\\u2009+\\u20093\\u2009=\\u20096 on biopsy. A multivariable Cox model was used to assess risk of biochemical recurrence, and multivariable logistic regression was used to assess risk of pathologic upgrading.', 'Eight hundred twenty-four men (27%) reported statin use at the time of radical prostatectomy. Statin users were older and had higher body mass index, higher Charlson Comorbidity Index, and lower pretreatment prostate-specific antigen values than statin nonusers. Over a median follow-up of 70 months (interquartile range: 36-107), a total of 455 men (15%) experienced biochemical recurrence. Statin use was not associated with biochemical recurrence (adjusted hazard ratio: 1.06, 95% confidence interval: 0.86-1.31). Of those men with biopsy Gleason 3\\u2009+\\u20093\\u2009=\\u20096 disease, 647 (52%) were upgraded to higher grade disease following radical prostatectomy; however, statin use was not associated with pathologic upgrading (adjusted odds ratio: 0.78, 95% confidence interval: 0.58-1.04).",
            "output": [
                "Is preoperative Statin Use at the Time of Radical Prostatectomy Associated With Biochemical Recurrence or Pathologic Upgrading?"
            ]
        },
        {
            "id": "task847-8e817d3291d244ac8b0fbd70a25df031",
            "input": "It is known that large dogs who are fed lamb and rice diets are at increased risk to develop taurine-deficiency-induced dilated cardiomyopathy. Since dogs obligatorily conjugate bile acids (BA) with taurine, we determined whether rice bran (RB) or other fibers (cellulose; CL, beet pulp; BP) would affect BA excretion and/or the taurine status of dogs.', 'Eighteen medium/large mixed-breed dogs were given purified diets containing CL, BP, or RB for 12\\xa0weeks. Taurine concentrations in plasma and whole blood were significantly decreased at week 12. The BP group, compared to the CL or RB groups, showed significantly lower taurine concentrations in plasma (6.5\\u2009\u00b1\\u20090.5 vs 20.4\\u2009\u00b1\\u20093.9 and 13.1\\u2009\u00b1\\u20092.0\\xa0\u03bcmol/L, respectively, P\\u2009<\\u20090.01, mean\\u2009\u00b1\\u2009SEM) and in whole blood (79\\u2009\u00b1\\u200910 vs 143\\u2009\u00b1\\u200914 and 127\\u2009\u00b1\\u200914\\xa0\u03bcmol/L, respectively, P\\u2009<\\u20090.01), lower apparent protein digestibility (81.9\\u2009\u00b1\\u20090.6 vs 88.8\\u2009\u00b1\\u20090.6 and 88.1\\u2009\u00b1\\u20091.2\\xa0%, respectively, P\\u2009<\\u20090.01), and higher BA excretions (5.6\\u2009\u00b1\\u20090.1 vs 3.4\\u2009\u00b1\\u20090.5 and 3.4\\u2009\u00b1\\u20090.4\\xa0\u03bcmol/g feces, respectively, P\\u2009<\\u20090.05) at week 12.",
            "output": [
                "Does dietary beet pulp decrease taurine status in dogs fed low protein diet?"
            ]
        },
        {
            "id": "task847-02284c9499744bb881b79ac33c015d55",
            "input": "Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Guidelines recommend cholesterol-lowering medication from 8 to 10 years of age and dietary recommendations. Little is known about the diet of FH children and the effect of dietary counseling. The aim of the study was to describe the diet of FH children with respect to fat quality, and to investigate if dietary counseling improved lipid profile.', 'Fifty-four FH children (5-18 years) were included in the study and dietary intake was recorded with a pre-coded food diary for four days. Information about plasma lipid levels was obtained.', 'Median intake of total fat, monounsaturated fat, polyunsaturated fat (PUFA) and saturated fat (SFA) was 30.8, 10.4, 5.9 and 12.0\\xa0E %, respectively. Among non-statin treated FH children, SFA intake was significantly correlated with TC, LDL-C and apolipoprotein (apo) B (rsp\\xa0=\\xa00.55; p\\xa0=\\xa00.004, rsp\\xa0=\\xa00.46; p\\xa0=\\xa00.02, and rsp\\xa0=\\xa00.45; p\\xa0=\\xa00.02, respectively), and PUFA/SFA ratio significantly inversely correlated with TC (rsp\\xa0=\\xa0-0.42; p\\xa0=\\xa00.03). Compared to the first visit, non-statin and non-plant sterol treated FH children (n\\xa0=\\xa010) had significantly reduced levels of TC (p\\xa0<\\xa00.01), LDL-C (p\\xa0=\\xa00.01), high-density lipoprotein cholesterol (p\\xa0=\\xa00.02), apo B (p\\xa0=\\xa00.05) and apo A-1 (p\\xa0=\\xa00.02) levels at a later visit.",
            "output": [
                "Is dietary counseling associated with an improved lipid profile in children with familial hypercholesterolemia?"
            ]
        },
        {
            "id": "task847-a40bb2393551480f9b5e1d70f01536a8",
            "input": "Affinity purification followed by mass spectrometry (AP/MS) is a widely used approach to identify protein interactions and complexes. In multicellular organisms, the accurate identification of protein complexes by AP/MS is complicated by the potential heterogeneity of complexes in different tissues. Here, we present an in vivo biotinylation-based approach for the tissue-specific purification of protein complexes from Caenorhabditis elegans. Tissue-specific biotinylation is achieved by the expression in select tissues of the bacterial biotin ligase BirA, which biotinylates proteins tagged with the Avi peptide.', 'We generated N- and C-terminal tags combining GFP with the Avi peptide sequence, as well as four BirA driver lines expressing BirA ubiquitously and specifically in the seam and hyp7 epidermal cells, intestine, or neurons. We validated the ability of our approach to identify bona fide protein interactions by identifying the known LGL-1 interaction partners PAR-6 and PKC-3. Purification of the Discs large protein DLG-1 identified several candidate interaction partners, including the AAA-type ATPase ATAD-3 and the uncharacterized protein MAPH-1.1. We have identified the domains that mediate the DLG-1/ATAD-3 interaction, and show that this interaction contributes to C. elegans development. MAPH-1.1 co-purified specifically with DLG-1 purified from neurons, and shared limited homology with the microtubule-associated protein MAP1A, a known neuronal interaction partner of mammalian DLG4/PSD95. A CRISPR/Cas9-engineered GFP::MAPH-1.1 fusion was broadly expressed and co-localized with microtubules.",
            "output": [
                "Does a tissue-specific protein purification approach in Caenorhabditis elegans identify novel interaction partners of DLG-1/Discs large?"
            ]
        },
        {
            "id": "task847-1283aadb00614c3f8d471e58232b0a79",
            "input": "A recurrent finding of trials on renal sympathetic denervation is a certain percentage of non-responders. The aim of this study was to examine the influence of arterial stiffness to predict response.', 'Eighty-eight patients were included in the study. Arterial stiffness was measured by invasive pulse wave velocity. Antihypertensive medication had to be unchanged during follow-up. Ambulatory blood pressure measurement (ABPM) was used to record blood pressure before and six months after denervation. Fifty-eight patients without changes in medication were included in the final analysis. Responders (n=37; blood pressure reduction -12.8\u00b16.4 mmHg) had a significantly lower pulse wave velocity (14.4\u00b14.4 m/s versus 17.7\u00b14.5 m/s; p=0.009) compared to non-responders (n=21; blood pressure reduction +3.0\u00b14.5 mmHg; p<0.001 for comparison with responders). In multivariate analysis, invasive pulse wave velocity was the only significant predictor of blood pressure reduction after denervation (odds ratio 1.15, 95% confidence interval [CI] 1.014-1.327; p=0.03). Patients with increased stiffness were older (p=0.001), had a higher prevalence of diabetes (p=0.008), more often had isolated systolic hypertension (p=0.007), and had a higher invasive pulse pressure (p<0.001).",
            "output": [
                "Does invasive aortic pulse wave velocity as a marker for arterial stiffness predict outcome of renal sympathetic denervation?"
            ]
        },
        {
            "id": "task847-a0fb9eb18ebf4947ab58eb77653f10a1",
            "input": "Metastasis is a primary cause of colorectal cancer (CRC)-related death, and cancer stem cells (CSCs) are thought to be majorly responsible for initiating metastatic behaviors. Doublecortin-like kinase 1 (DCLK1) was recently discovered to be a marker for gastrointestinal CSCs. Here, we aimed to explore whether DCLK1 is associated with CRC metastasis through clinical and in vitro investigations.', 'The expression levels of DCLK1 mRNA and protein in human CRC tissues were analyzed through quantitative RT-PCR and immunohistochemistry staining, respectively. Human CRC cell line SW480 was selected to explore the effect of DCLK1 overexpression on cell migration and invasion. Besides, the associations between DCLK1 and epithelial-mesenchymal transition (EMT) were determined.', 'Compared to normal colorectal tissues, DCLK1 expression was significantly up-regulated in human CRC tissues and correlated well with high lymphatic metastasis and poor prognosis in patients. DCLK1 expression was inversely associated with overall survival in CRC patients. Overexpression of DCLK1 in SW480 cells markedly promoted cell migration and invasion. Furthermore, we validated that DCLK1 could facilitate EMT in cancer cells by up-regulation of the mesenchymal markers Vimentin and ZEB1 and down-regulation of the epithelial marker E-cadherin in SW480 cells.",
            "output": [
                "Is dCLK1 up-regulated and associated with metastasis and prognosis in colorectal cancer?"
            ]
        },
        {
            "id": "task847-a131d8a1cc6e4aa68bebcd8a670f5866",
            "input": "To define the predictive capability of serum C-reactive protein for a contemporary patient collective undergoing metastasectomy for metastatic renal cell carcinoma with access to modern targeted therapies.', 'A total of 88 patients treated with metastasectomy for metastatic renal cell carcinoma from 2003 to 2014 were evaluated for putative clinicopathological risk factors and survival. Kaplan-Meier analyses, univariate and multivariate testing were carried out. Receiver operating characteristic curve analysis was applied to evaluate available risk stratification instruments for patients undergoing metastasectomy.', 'Median overall survival for the collective was 66.31 months (95% confidence interval 50.67-135.47; 5-year overall survival 55%). The median preoperative C-reactive protein level was 6.7 mg/L (range 0.1-161.7). A C-reactive protein cut-off value of 5 mg/dL was significantly discriminative of survival (P = 0.029). Median survival in dependence of C-reactive protein accounted for 50.67 months (range 33.86-63.05 months) in the C-reactive protein >5 mg/L group, and 135.47 months in the C-reactive protein \u22645 mg/L group (range 66.31-135.47 months). C-reactive protein elevation >5 mg/L, anemia and surgical margin status were identified as significant predictors of overall survival in univariate analysis. In a multivariate model, resection margin status (P = 0.015) and C-reactive protein elevation (P = 0.038) were confirmed as independent predictive variables.",
            "output": [
                "Is metastasectomy for metastatic renal cell carcinoma in the era of modern systemic treatment : C-reactive protein an independent predictor of overall survival?"
            ]
        },
        {
            "id": "task847-1a9287342dcc4bbf86c30601b52afbe7",
            "input": "Young children with sickle cell disease (SCD) are at risk for cognitive delay. In addition to biologic risk factors associated with SCD, environmental factors contribute to cognitive dysfunction within this cohort.', 'We completed a single-arm, prospective cohort study. Children with SCD between the ages of 3 and 36 months and their caregivers were followed between October 2010 and December 2013. The aim was to describe the role of a home visitation model, the home environment, and socioeconomic status in the development of young children with SCD. Primary outcome measures were the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and the Home Observation for Measurement of the Environment (HOME). We hypothesized that the home visitation model, Parents as Teachers', 'Thirty-five participants had at least two PAT visits and BSID-III assessments. Mean scores within all five subtests of the BSID-III improved between enrollment and exit, with significant changes within cognitive (P = 0.016) and expressive language (EL) domains (P = 0.002). Multivariate modeling found the HOME score associated with the exit results of the cognitive domain.",
            "output": [
                "Does a pilot study of parent education intervention improve early childhood development among toddlers with sickle cell disease?"
            ]
        },
        {
            "id": "task847-ab65677aca1c4e68b9a16af4be7c6fec",
            "input": "To determine the rate of persistent tracheocutaneous fistula (TCF) in pediatric patients managed with stomal maturation at the time of the tracheostomy.', 'Retrospective chart analysis of all cases of tracheostomy performed at a tertiary pediatric care center between 2001 and 2011.', 'The use of stomal maturation, number of decannulations, number of persistent TCFs, timing of TCF repair, and the overall mortality were assessed.', 'A total of 264 patients received tracheostomy between 2001 and 2011. Of the total, 173 (66%) underwent stomal maturation. Of those 173 patients, 89 patients (51% of maturation group) underwent planned decannulation. Forty seven (53%) of the 89 decannulated were found to have a persistent TCF in the stomal maturation group. These were diagnosed an average of 1.3 years (range, 4-43 months) after decannulation. Of the 91 patients (34% of the total) who did not undergo stomal maturation, 44 (48% of nonmaturation group) underwent planned decannulation. Twenty of the 44 patients decannulated (45%) were diagnosed with a residual TCF 8 to 28 months later. Both groups achieved similar rates of decannulation (51% maturation vs. 48% non-maturation [P\\u2009=\\u2009.80]) and TCF (27% maturation vs. 22% non-maturation [P\\u2009=\\u2009.44]). Overall, mortality rates were (32/173) 18% (matured) versus (26/91) 29% (nonmatured). No mortalities were tracheostomy related. The mean (standard deviation) time from operation to TCF closure among those with TCF was 4.0 (1.9) years.",
            "output": [
                "Does stomal maturation increase the rate of tracheocutaneous fistulas?"
            ]
        },
        {
            "id": "task847-0dddb8ef8c88479c831fe83d861945ea",
            "input": "Areas of high signal intensity (HighT2) on T2-weighted cardiovascular magnetic resonance (CMR) imaging have been demonstrated in hypertrophic cardiomyopathy (HCM). It has been hypothesised that HighT2 may indicate active tissue injury in HCM. In this context, we studied HighT2 in relation to cardiac troponin.', 'Outpatient HCM patients without a history of coronary artery disease underwent CMR imaging at 1.5\\u2005T using T2-weighted, cine and late gadolinium enhancement (LGE) imaging to assess HighT2, left ventricular (LV) function, LV mass and the presence and extent of LGE. Highly sensitive cardiac troponin T (hs-cTnT) was assessed as a marker of injury, with hs-cTnT \u226514 and >3\\u2005ng/L defined as an elevated and detectable troponin.', \"HighT2 was present in 28% of patients (28/101). An elevated hs-cTnT was present in 54% of patients with HighT2 (15/28) compared with 14% of patients without HighT2 (10/73) (p<0.001). Hs-cTnT was detectable in 96% of patients with HighT2 (27/28) compared with 66% of patients without HighT2 (48/73) (p=0.002). In case of an undetectable hs-cTnT, HighT2 was only seen in 4% (1/26). In addition, the extent of HighT2 was related with increasing hs-cTnT concentrations (Spearman's \u03c1: 0.42, p<0.001).",
            "output": [
                "Is high T2-weighted signal intensity associated with elevated troponin T in hypertrophic cardiomyopathy?"
            ]
        },
        {
            "id": "task847-b545275566c940abad49aa951702734a",
            "input": "Comparison of the efficacy of tropicamide eyedrops to the combination of 0.5% tropicamide and 5% phenylephrine eyedrops in order to achieve a proper dilation in premature infants undergoing screening for retinopathy of prematurity.', 'A prospective, randomized, double-blind study was conducted to compare the efficacy of two mydriatic regimens: one regimen consisting of three drops of 0.5% tropicamide (TTT regimen), the other regimen consisting of one drop of 5% phenylephrine and two drops of 0.5% tropicamide (PTT regimen). Thirty premature infants were enrolled and received both mydriatic regimens: one regimen in each eye. Outcomes were pupil dilation evaluated by the percentage of pupil diameter over cornea diameter, the percentage of pupil surface over cornea surface and the quality of the eye fundus examination.', 'The percentage of pupil diameter over cornea diameter was 47.3% (\u00b18.7) with the TTT regimen and 65.9% (\u00b18.8) with the PTT regimen (p\\xa0<\\xa00.0001). The percentage of pupil surface over cornea surface was 23.1% (\u00b18.3) with the TTT regimen and 43.8% (\u00b17.3) with the PTT regimen (p\\xa0<\\xa00.0001). Thus, the pupil surface area was 1.9 times greater with the PTT than with the TTT regimen. Visualization of the retinal periphery was possible for 30 of 30 eyes dilated with the PTT regimen and for 16 of 30 eyes dilated with the TTT regimen (p\\xa0<\\xa00.0001).",
            "output": [
                "Is combination of 5 % phenylephrine and 0.5 % tropicamide eyedrops for pupil dilation in neonates twice as effective as 0.5 % tropicamide eyedrops alone?"
            ]
        },
        {
            "id": "task847-e8eed1f2c3764d22a00644ca92c5f526",
            "input": "Our objective was to identify the antioxidant properties of honeybee products from Turkey, chestnut honey, pollen, propolis, and royal jelly, and their hepatoprotective activity against CCl4-induced hepatic damage in rats.', 'Animals were fed with honeybee products for 7 days following CCl4 injection. Development of liver damage and oxidative stress were monitored by measuring the activities of the enzymes alanine transaminase, aspartate transaminase, malondialdehyde, superoxide dismutase, and catalase. Antioxidant capacities of the bee products were identified using FRAP and DPPH assays, as well as by measuring total phenolic and flavonoid contents.', 'The antioxidant activities of the honeybee products were highest in propolis, followed, in order, by pollen, honey, and royal jelly. Despite their different levels of antioxidant capacity, their roles in the prevention of liver damage induced by CCl4 were very similar, which can be explained through their bioavailability to the treated animals.",
            "output": [
                "Do apitherapy products enhance the recovery of CCL4-induced hepatic damages in rats?"
            ]
        },
        {
            "id": "task847-060c4fb28b5e4c419e9b4c714ad54bf8",
            "input": "In order to determine the synergistic effects of human placental mesenchymal stem cells (PMSCs) on hematopoiesis in vivo, we compared the intrabone marrow injection (IBMI) with the conventional intravenous injection (IVI).', 'C57BL/6 recipient mice conditioned with lethal doses of irradiation were transplanted with bone marrow mononuclear cells (MNCs) and bone marrow-derived mesenchymal stem cells (BMSCs) from BALB/c mice by IBMI or IVI. NOD/SCID recipient mice conditioned with sublethal doses of irradiation were transplanted with human umbilical cord blood MNCs (UCB-MNCs) and PMSCs by IBMI or IVI.', 'The number of hematopoietic cells was significantly higher in mice transplanted with BMSCs by IBMI than in those transplanted by IVI in a murine transplantation model (BALB/c\u2192C57BL/6). Moreover, the percentage of human hematopoietic cells in the tibiae of the NOD/SCID mice that were transplanted with PMSCs plus UCB-MNCs was higher than that in mice transplanted with UCB-MNCs alone. In addition, in mice that were transplanted with PMSCs, PMSCs injected by IBMI were more efficient than those injected by IVI.",
            "output": [
                "Does intrabone marrow injection enhance placental mesenchymal stem cellmediated support of hematopoiesis in mice?"
            ]
        },
        {
            "id": "task847-3be0d1cb330145ebbb36f6f8bfaa3065",
            "input": "The chronic inflammation plays an important role in heart failure and complement components might be useful markers of the prognosis. We set out to evaluate their predictive value in the clinical outcomes of patients with cardiac resynchronization therapy (CRT).', 'We determined the complement levels C3, C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP) of 126 heart failure patients in a prospective, single-center observational study before and 6\\xa0months after CRT implantation.', 'CRT reduced the C3a [212.5 (148.2-283.6) vs. 153 (119.8-218.3)\\xa0ng/mL, p\\xa0<\\xa00.0001] and the sC5b-9 levels [296.9 (234.2-358.8) vs. 255.1 (210.1-319.0)\\xa0ng/mL, p\\xa0=\\xa00.0006], but not the total C3 levels [1.43 (1.26-1.61) vs. 1.38 (1.23-1.57) g/L, p\\xa0=\\xa00.57]. C3a predicted the 5-year mortality of the patients [C3a\\xa0>\\xa0165\\xa0ng/mL hazard ratio\\xa0=\\xa04.21 (1.65-10.72), p\\xa0=\\xa00.003] independent of the NT-proBNP and other factors. After reclassification, we observed a significant net reclassification improvement [NRI\\xa0=\\xa00.71 (0.43-0.98), p\\xa0<\\xa00.0001] and integrated discrimination improvement [IDI\\xa0=\\xa00.08 (0.03-0.12), p\\xa0=\\xa00.0002].",
            "output": [
                "Does complement C3a predict outcome in cardiac resynchronization therapy of heart failure?"
            ]
        },
        {
            "id": "task847-0282350d7e9048158afe2347a5a9db92",
            "input": "Accumulating evidences indicated that lncRNAs play crucial regulatory roles in oncogenesis and progression of cancers. BRAF activated non-coding RNA (BANCR) has been identified to contribute to the progression of some human cancers. However, the relationship between BANCR and bladder cancer (BC) is largely unclear.', 'BANCR expression levels in BC, paired non-cancer tissues and BC cell lines were detected by real-time quantitative RT-PCR (qRT-PCR). The relationships between BANCR expression levels and the clinical characteristics were evaluated. BANCR expression was enhanced by transfecting a pcDNA-BANCR vector. We used both CCK-8 assay and Edu assay to detect cell proliferation. We also detect cell apoptosis and migration by using ELISA assay, Flow cytometry and transwell assay, respectively. All statistical analyses were executed by using the SPSS 20.0 software.', 'BANCR expression levels were remarkably decreased in BC tissues compared with adjacent noncancerous tissues. BANCR expression levels in two BC cell lines were also significantly down-regulated. Clinicopathologic analysis revealed that low BANCR expression was positively correlated with TNM stage, but not associated with other clinicopathological characteristics. BANCR has been successfully overexpressed in BC cell lines (T24 and SW780) by transfecting a pcDNA-BANCR vector. Cell proliferation inhibition, apoptosis induction and migration suppression were also observed in pCDNA-BANCR-transfected T24 and SW780 cells.",
            "output": [
                "Does over-expression of long noncoding RNA BANCR inhibit malignant phenotypes of human bladder cancer?"
            ]
        },
        {
            "id": "task847-22ba28ceeb874ad6a949fc56d44f227d",
            "input": "In the context of advanced immunosuppression, M. tuberculosis is known to cause detectable mycobacteremia. However, little is known about the intra-patient mycobacterial microevolution and the direction of seeding between the sputum and blood compartments.', 'From a diagnostic study of HIV-infected TB patients, 51 pairs of concurrent blood and sputum M. tuberculosis isolates from the same patient were available. In a previous analysis, we identified a subset with genotypic concordance, based on spoligotyping and 24 locus MIRU-VNTR. These paired isolates with identical genotypes were analyzed by whole genome sequencing and phylogenetic analysis.', 'Of the 25 concordant pairs (49\\xa0% of the 51 paired isolates), 15 (60\\xa0%) remained viable for extraction of high quality DNA for whole genome sequencing. Two patient pairs were excluded due to poor quality sequence reads. The median CD4 cell count was 32 (IQR; 16-101)/mm(3) and ten (77\\xa0%) patients were on ART. No drug resistance mutations were identified in any of the sequences analyzed. Three (23.1\\xa0%) of 13 patients had SNPs separating paired isolates from blood and sputum compartments, indicating evidence of microevolution. Using a phylogenetic approach to identify the ancestral compartment, in two (15\\xa0%) patients the blood isolate was ancestral to the sputum isolate, in one (8\\xa0%) it was the opposite, and ten (77\\xa0%) of the pairs were identical.",
            "output": [
                "Does whole genome sequencing reveal mycobacterial microevolution among concurrent isolates from sputum and blood in HIV infected TB patients?"
            ]
        },
        {
            "id": "task847-cd4fadf38e564234b61459afe2ab1075",
            "input": "Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas.', 'We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior.', 'We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS. Patients were divided into clinical groups 1 to 4 representing best to worst clinical behavior. The association among IMS findings, histopathological diagnoses, and clinical groups was assessed.', 'There was a strong association between a diagnosis of Spitzoid melanoma by IMS and lesions categorized as clinical groups 2, 3, and 4 (recurrence of disease, metastases, or death) compared with clinical group 1 (no recurrence or metastasis beyond a sentinel node) (P\\xa0<\\xa0.0001). Older age and greater tumor thickness were strongly associated with poorer outcome (P\\xa0=\\xa0.01).",
            "output": [
                "Does imaging mass spectrometry assist in the classification of diagnostically challenging atypical Spitzoid neoplasms?"
            ]
        },
        {
            "id": "task847-e777c7be476942a8bdb571bf4bcabac4",
            "input": "Declines in skeletal muscle structure and function are found in various clinical populations, but the intramuscular proteolytic pathways that govern declines in these individuals remain relatively poorly understood. The nematode Caenorhabditis elegans has been developed into a model for identifying and understanding these pathways. Recently, it was reported that UNC-105/degenerin channel activation produced muscle protein degradation via an unknown mechanism.', 'Generation of transgenic and double mutant C.\\u2009elegans, RNAi, and drug treatments were utilized to assess molecular events governing protein degradation. Western blots were used to measure protein content. Cationic dyes and adenosine triphosphate (ATP) production assays were utilized to measure mitochondrial function.', 'unc-105 gain-of-function mutants display aberrant muscle protein degradation and a movement defect; both are reduced in intragenic revertants and in let-2 mutants that gate the hyperactive UNC-105 channel. Degradation is not suppressed by interventions suppressing proteasome-mediated, autophagy-mediated, or calpain-mediated degradation nor by suppressors of degenerin-induced neurodegeneration. Protein degradation, but not the movement defect, is decreased by treatment with caspase inhibitors or RNAi against ced-3 or ced-4. Adult unc-105 muscles display a time-dependent fragmentation of the mitochondrial reticulum that is associated with impaired mitochondrial membrane potential and that correlates with decreased rates of maximal ATP production. Reduced levels of CED-4, which is sufficient to activate CED-3 in vitro, are observed in unc-105 mitochondrial isolations.",
            "output": [
                "Does degenerin channel activation cause caspase-mediated protein degradation and mitochondrial dysfunction in adult C. elegans muscle?"
            ]
        },
        {
            "id": "task847-8c5de390bc104825b4a133cd50e6ccae",
            "input": "We investigated the pathway of autophagy signaling linked to sarcopenia of mice.', 'Young adult (3-month) and aged (24- month) C57BL/6J mice were used. Using real-time PCR, Western blotting, and immunohistochemical microscopy, we evaluated the amounts of p62/SQSTM1, LC3, and Beclin-1 in the quadriceps muscle change with aging in mice.', 'Marked fiber atrophy (30%) and many fibers with central nuclei were observed in the aged mice. Western blotting using homogenate of the cytosolic fraction clearly showed that the amounts of p62/SQSTM1 and Beclin-1 proteins were significantly increased in the aged skeletal muscle. The amounts of these proteins in both nuclear and membrane fractions did not change significantly with age. Immunofluorescence labeling indicated that aged mice more frequently possessed p62/SQSTM1-positive fibers in the cytosol in quadriceps muscle than young ones (aged: 14% vs. young: 1%). In aged muscle, p62/SQSTM1-positive fibers were significantly smaller than the surrounding p62/SQSTM1-negative fibers. Aging did not elicit significant changes in the mRNA levels of p62/SQSTM1 and Beclin-1, but decreased LC3 mRNA level. In aged muscle, the location of p62/SQSTM1 immunoreactivity was similar to that of Beclin-1 protein, but not LC3.",
            "output": [
                "Is p62/SQSTM1 but not LC3 accumulated in sarcopenic muscle of mice?"
            ]
        },
        {
            "id": "task847-52f741e347844fe99ef370636b73eed7",
            "input": "Cachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one-third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer-associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti-fatigue, anti-ageing, and anti-Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery.\", 'In the murine models of cachexia induced by CT-26 and Lewis lung carcinoma (LLC) tumour, respectively, main features of CAC were determined after treatment of salidroside or chemotherapy. In vitro experiments were performed using murine C2C12 myotubes, which were treated by tumour necrosis factor-\u03b1. Levels of several critical muscle-related signal proteins such as mammalian target of rapamycin (mTOR), p-mTOR, and myosin heavy chain (MyHC) were examined using western blot both in vitro and in vivo.', 'In the present study, we showed the exciting effect of salidroside on the treatment of CAC. In CT-26 and LLC models, respectively, salidroside treatment could effectively preserve the tumour-free body weight, decrease loss of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their survival time. Additionally, in combined chemotherapy, salidroside could synergistically enhance the anti-tumour activity of cisplatin, especially decreased or eliminated chemotherapy-induced cachexia. Further analysis demonstrated that salidroside could significantly increase expression of mTOR, p-mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that salidroside could not only obviously increase mTOR, p-mTOR, and MyHC expression in C2C12 myotubes but also effectively rescue their down-regulation induced by tumour necrosis factor-\u03b1.",
            "output": [
                "Does salidroside alleviate cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling?"
            ]
        },
        {
            "id": "task847-406c0b2ba7f240b79526b33dd3cf7941",
            "input": "Calcitonin gene-related peptide (CGRP) is thought be involved in the modulation of intestinal motility. CGRP receptor is composed of receptor activity-modifying protein (RAMP) 1 combined with calcitonin receptor-like receptor (CRLR) for CGRP. We investigated the role of CGRP in mice with experimentally induced colitis.', 'We used dextran sodium sulfate (DSS) to induce colitis in mice. We compared the severity of colitis in wild-type (WT) mice, mice treated with a CGRP receptor antagonist (CGRP', 'The severity of inflammation in DSS-induced colitis increased markedly in CGRP",
            "output": [
                "Does rAMP1 suppress mucosal injury from dextran sodium sulfate-induced colitis in mice?"
            ]
        },
        {
            "id": "task847-be677fe5d40e4f9ab1f805d87f375ca2",
            "input": "In this study, we compared the success of sinus lifting and alternative treatment methods in applying dental implants in cases lacking adequate bone due to pneumatization of the maxillary sinus.', 'In a computer environment, 3D models were created using computerized tomography data from a patient. Additionally, implants and abutments were scanned at the macroscopic level, and the resulting images were transferred to the 3D models. Five different models were examined: a control model, lateral sinus lifting (LSL), short dental implant placement (SIP), tilted implant placement (TIP) and distal prosthetic cantilever (DC) use. Vertical and oblique forces were applied in each model. The compression, tension and von Mises stresses in each model were analyzed by implementing a finite element analysis method.', 'In our study, the LSL method was observed to be the closest to the control model. The TIP model showed high stress values under conditions of oblique forces but showed successful results under conditions of vertical forces, and the opposite results were observed in the SIP model. The DC model provided the least successful results among all models.",
            "output": [
                "Do biomechanical comparison of sinus floor elevation and alternative treatment methods for dental implant placement?"
            ]
        },
        {
            "id": "task847-e8551e3bbeaf470498e6a61aa68319eb",
            "input": "Lipopolysaccharide (LPS)-induced preconditioning protects neurons against traumatic spinal cord injury (TSCI) in rats. This study sought to test whether Nrf2, a transcription factor, mediated LPS-induced preconditioning.', 'The TSCI model was established using a standardized NYU impactor on adult female rats. Rats were pretreated with LPS (0.2mg/kg, IP; 72h before injury). Nrf2 was silenced by injecting a lentivirus encoding RNAi against Nrf2 into injured spinal cords. Neurologic function was assessed by Basso, Beattie and Bresnahan (BBB) scores 6h, 12h, 24h, 48h, 72h, 7d and 14d after TSCI. Neuronal apoptosis was measured by a TUNEL staining. Ultrastructure was observed using transmission electron microscope (TEM). The protein expression of HO-1, NQO1 and GCLC was examined using immunohistochemistry and immunoblotting.', 'The injection of a lentivirus effectively transfected GFP into injured spinal cords. The expression of Nrf2 was significantly decreased in spinal cords receiving a lentivirus encoding RNAi against Nrf2. BBB scores showed that TSCI markedly impaired nervous function, which was markedly preserved by LPS pretreatment. Nrf2 knockdown significantly suppressed LPS pretreatment-induced protection of nervous function. TEM images and TUNEL staining showed an increase in apoptotic cells when Nrf2 was silenced. Moreover, immunohistochemistry and immunoblotting analysis exhibited that LPS pretreatment significantly upregulated the expression of anti-oxidative proteins including HO-1, NQO1 and GCLC, which was suppressed when Nrf2 expression was silenced in injured spinal cords.",
            "output": [
                "Does lipopolysaccharide-induced preconditioning protect against traumatic spinal cord injury by upregulating Nrf2 expression in rats?"
            ]
        },
        {
            "id": "task847-28fcafd3c9d04f1aa589db2d14b73459",
            "input": "The receptor for activated protein kinase C (RACK1) is a scaffold protein involved in multiple intracellular signal pathways. Previous studies have shown that RACK1 is associated with the progression of multiple cancer types, including hepatocellular carcinoma and gastric cancer. However, the role of RACK1 in human pancreatic ductal adenocarcinoma (PDAC) remains unclear.', 'In this study, the expression of RACK1 was evaluated by Western blot analysis in 8 paired fresh PDAC tissues and immunohistochemistry on 179 paraffin-embedded slices. Then, we used Fisher exact test to analyze the correlation between RACK1 expression and clinicopathological characteristics. Starvation and re-feeding assay was used to assess cell cycle. Western blot, CCK8, flow cytometry assays, and colony formation analyses demonstrated that RACK1 played an essential role in PDAC development. Annexin-V/PI apoptotic assay and western blot showed that RACK1 was involved in regulating the apoptosis of PDAC cells.', \"RACK1 was highly expressed in PDAC tissues and cell lines and was significantly associated with multiple clinicopathological factors. Univariate and multivariate analyses showed that high RACK1 expression was identified to be an independent prognostic factor for PDAC patients' survival. In vitro, serum starvation-refeeding experiment suggested that RACK1 was upregulated in proliferating PDAC cells, together with the percentage of cells at the S phase, and was correlated with the expression of Cyclin D1. Moreover, Overexpression of RACK1 facilitated the proliferation and cell cycle progression of PDAC cells, while downregulation of RACK1 induced growth impairment, G1/S cell cycle arrest and apoptosis in PDAC cells. Silencing RACK1 decreased bcl-2 expression, increased cleaved caspase3 expression level and induced the apoptosis of PDAC cells.",
            "output": [
                "Does rACK1 overexpression associate with pancreatic ductal adenocarcinoma growth and poor prognosis?"
            ]
        },
        {
            "id": "task847-4a48cc8c7ec641b8a42b851a26da62f4",
            "input": "Glioblastoma (GBM) tumors exhibit strong phenotypic differences that can be quantified using magnetic resonance imaging (MRI), but the underlying biological drivers of these imaging phenotypes remain largely unknown. An Imaging-Genomics analysis was performed to reveal the mechanistic associations between MRI derived quantitative volumetric tumor phenotype features and molecular pathways.', 'One hundred fourty one patients with presurgery MRI and survival data were included in our analysis. Volumetric features were defined, including the necrotic core (NE), contrast-enhancement (CE), abnormal tumor volume assessed by post-contrast T1w (tumor bulk or TB), tumor-associated edema based on T2-FLAIR (ED), and total tumor volume (TV), as well as ratios of these tumor components. Based on gene expression where available (n\\u2009=\\u200991), pathway associations were assessed using a preranked gene set enrichment analysis. These results were put into context of molecular subtypes in GBM and prognostication.', 'Volumetric features were significantly associated with diverse sets of biological processes (FDR\\u2009<\\u20090.05). While NE and TB were enriched for immune response pathways and apoptosis, CE was associated with signal transduction and protein folding processes. ED was mainly enriched for homeostasis and cell cycling pathways. ED was also the strongest predictor of molecular GBM subtypes (AUC\\u2009=\\u20090.61). CE was the strongest predictor of overall survival (C-index\\u2009=\\u20090.6; Noether test, p\\u2009=\\u20094x10(-4)).",
            "output": [
                "Does imaging-genomics reveal driving pathways of MRI derived volumetric tumor phenotype features in Glioblastoma?"
            ]
        },
        {
            "id": "task847-6fa6c7eb476042f190da6928c89e7715",
            "input": "Transfusion of packed erythrocytes stored for a long duration is associated with increased pulmonary arterial pressure and vascular resistance. Prolonged storage decreases erythrocyte deformability, and older erythrocytes are rapidly removed from the circulation after transfusion. The authors studied whether treating stored packed ovine erythrocytes with NO before transfusion could prevent pulmonary vasoconstriction, enhance erythrocyte deformability, and prolong erythrocyte survival after transfusion.', 'Ovine leukoreduced packed erythrocytes were treated before transfusion with either NO gas or a short-lived NO donor. Sheep were transfused with autologous packed erythrocytes, which were stored at 4\u00b0C for either 2 (\"fresh blood\") or 40 days (\"stored blood\"). Pulmonary and systemic hemodynamic parameters were monitored before, during, and after transfusion. Transfused erythrocytes were labeled with biotin to measure their circulating lifespan. Erythrocyte deformability was assessed before and after NO treatment using a microfluidic device.', 'NO treatment improved the deformability of stored erythrocytes and increased the number of stored erythrocytes circulating at 1 and 24\\u2009h after transfusion. NO treatment prevented transfusion-associated pulmonary hypertension (mean pulmonary arterial pressure at 30\\u2009min of 21\\u2009\u00b1\\u20091 vs. 15\\u2009\u00b1\\u20091 mmHg in control and NO-treated packed erythrocytes, P < 0.0001). Washing stored packed erythrocytes before transfusion did not prevent pulmonary hypertension.",
            "output": [
                "Does exposure of Stored Packed Erythrocytes to Nitric Oxide prevent Transfusion-associated Pulmonary Hypertension?"
            ]
        },
        {
            "id": "task847-be4950bcf4c541748032057d038c66e7",
            "input": "This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sj\u00f6gren's syndrome (pSS).\", \"Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sj\u00f6gren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.\", '14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines-interferon-\u03b3-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-\u03b1 (p=0.046), lymphotoxin-\u03b1 (p=0.034) and interferon-\u03b3 (IFN-\u03b3) (p=0.022)-were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-\u03b3 (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.",
            "output": [
                "Is fatigue in primary Sj\u00f6gren 's syndrome associated with lower levels of proinflammatory cytokines?"
            ]
        },
        {
            "id": "task847-ec8e5b71f2864936b33aa12456637741",
            "input": "Lower respiratory tract infection is a common cause of consultation and antibiotic prescription in paediatric practice. The misuse of antibiotics is a major cause of the emergence of multidrug-resistant bacteria. The aim of this study was to evaluate the frequency, changes over time, and determinants of non-compliance with antibiotic prescription recommendations for children admitted in paediatric emergency department (PED) with community-acquired pneumonia (CAP).', 'We conducted a prospective two-period study using data from the French pneumonia network that included all children with CAP, aged one month to 15\\xa0years old, admitted to one of the ten participating paediatric emergency departments. In the first period, data from children included in all ten centres were analysed. In the second period, we analysed children in three centers for which we collected additional data. Two experts assessed compliance with the current French recommendations. Independent determinants of non-compliance were evaluated using a logistic regression model. The frequency of non-compliance was compared between the two periods for the same centres in univariate analysis, after adjustment for confounding factors.', 'A total of 3034 children were included during the first period (from May 2009 to May 2011) and 293 in the second period (from January to July 2012). Median ages were 3.0\\xa0years [1.4-5] in the first period and 3.6\\xa0years in the second period. The main reasons for non-compliance were the improper use of broad-spectrum antibiotics or combinations of antibiotics. Factors that were independently associated with non-compliance with recommendations were younger age, presence of risk factors for pneumococcal infection, and hospitalization. We also observed significant differences in compliance between the treatment centres during the first period. The frequency of non-compliance significantly decreased from 48 to 18.8\\xa0% between 2009 and 2012. The association between period and non-compliance remained statistically significant after adjustment for confounding factors. Amoxicillin was prescribed as the sole therapy significantly more frequently in the second period (71\\xa0% vs. 54.2\\xa0%, p\\u2009<\\u20090.001).",
            "output": [
                "Is compliance with the current recommendations for prescribing antibiotics for paediatric community-acquired pneumonia improving : data from a prospective study in a French network?"
            ]
        },
        {
            "id": "task847-69fd48b801bd4cf9a13b3751f14c83d4",
            "input": "Pectins are one of the main components of plant cell walls. They are secreted to the wall as highly methylesterified forms that can be de-esterified by pectin methylesterases (PMEs). The degree of methylesterification of pectins changes during development, PMEs are involved in the cell wall remodeling that occurs during diverse plant developmental processes. Nevertheless, the functional meaning of pectin-related wall remodeling in different cell types and processes remains unclear. In vivo, the microspore follows the gametophytic pathway and differentiates to form the pollen grain. In vitro, the microspore can be reprogrammed by stress treatments becoming a totipotent cell that starts to proliferate and follows the embryogenic pathway, a process known as microspore embryogenesis.', 'To investigate if the change of developmental programme of the microspore towards embryogenesis involves changes in pectin esterification levels, which would cause the cell wall remodeling during the process, in the present study, dynamics of PME expression and degrees of pectin esterification have been analysed during microspore embryogenesis and compared with the gametophytic development, in Brassica napus. A multidisciplinary approach has been adopted including BnPME gene expression analysis by quantitative RT-PCR, fluorescence in situ hybridization, immuno-dot-blot and immunofluorescence with JIM5 and JIM7 antibodies to reveal low and highly-methylesterified pectins. The results showed that cell differentiation at advanced developmental stages involved induction of BnPME expression and pectin de-esterification, processes that were also detected in zygotic embryos, providing additional evidence that microspore embryogenesis mimics zygotic embryogenesis. By contrast, early microspore embryogenesis, totipotency and proliferation were associated with low expression of BnPME and high levels of esterified pectins.",
            "output": [
                "Is bnPME progressively induced after microspore reprogramming to embryogenesis , correlating with pectin de-esterification and cell differentiation in Brassica napus?"
            ]
        },
        {
            "id": "task847-eae7c861345a418194be3da45bbb23c0",
            "input": "Nitrofurantoin is a nitroderivative antibiotic that has bactericidal activity against pathogens causing urinary tract infection. A few studies have reported that nitrofurantoin has cytotoxic activity against cancer cells; however, nitrofurans remain a poorly explored class of compounds with respect to their anticancer potential. The aim of this study was to investigate the anticancer effects of a nitrofurantoin derivative, n-pentyl-nitrofurantoin (NFP), on HL-60 leukemia cells.', 'Cytotoxicity was assayed by the MTT assay. Cell morphology and phosphatidylserine externalization were visualized after Giemsa-May-Grunwald and annexin V staining, respectively. DNA content and mitochondrial depolarization were measured by flow cytometry. BAX and BCL-xL expression was examined by RT-PCR.', 'NFP was 3.8-fold more cytotoxic against HL-60 leukemia cells than against normal cells. NFP reduced the number of viable cells 24h after the treatment with a concomitant increase in the number of apoptotic cells indicated by the externalization of phosphatidylserine, DNA fragmentation, and mitochondrial depolarization. The mRNA levels of BAX increased, whereas the mRNA levels of BCL-xL decreased.",
            "output": [
                "Does n-pentyl-nitrofurantoin induce apoptosis in HL-60 leukemia cell line by upregulating BAX and downregulating BCL-xL gene expression?"
            ]
        },
        {
            "id": "task847-46a29b2de1a043b98de0a1fd46966eba",
            "input": "The isoflavone puerarin [7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one 8-(\u03b2-D-glucopyranoside)] possesses many biological activities. In this study, we investigated the effects of puerarin on adhesion molecules (AMs), including serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin), and the activation of nuclear factor kappa B (NF-\u03baB) in rabbits with experimental atherosclerosis.', 'In total, 24 rabbits were divided into control (standard diet), high-lipid diet (HLD), and PUE (HLD supplemented with puerarin) groups. At the end of weeks 0, 8, and 16, serum levels of AMs were measured. At the end of week 16, the thickness of the intima was detected. Protein and mRNA levels of AMs were checked by immunohistochemistry and RT-PCR, respectively. Protein levels of p65 NF-\u03baB and phosphorylation of inhibitor-\u03baB (I-\u03baB) were investigated by Western blotting.', 'Atherosclerotic lesions in the thoracic arch were found in the HLD and PUE groups, but not in the control group. Compared with the HLD group, the thickness of the intima in the PUE group was reduced. Our results indicate that puerarin reduced the protein and mRNA levels of AMs in this rabbit model. We also found that the reduced AM levels were due to inhibition of the phosphorylation and degradation of I-\u03baB, resulting in reduced p65 NF-\u03baB nuclear translocation.",
            "output": [
                "Does puerarin inhibit the inflammatory response in atherosclerosis via modulation of the NF-\u03baB pathway in a rabbit model?"
            ]
        },
        {
            "id": "task847-cf9a076b8afd431db8c79d7a5c03db42",
            "input": "Plant genomes are populated by different types of repetitive elements including transposable elements (TEs) and simple sequence repeats (SSRs) that can have a strong impact on genome size and dynamic as well as on the regulation of gene transcription. At least two-thirds of the tomato genome is composed of repeats. While their bulk impact on genome organization has been recently revealed by whole genome assembly, their influence on tomato biology and phenotype remains largely unaddressed. More specifically, the effects and roles of DNA repeats on the maturation of fleshy fruits, which is a complex process of key agro-economic interest, still needs to be investigated comprehensively and tomato is arguably an excellent model for such study.', 'We have performed a comprehensive annotation of the tomato repeatome to explore its potential impact on tomato genome composition and gene transcription. Our results show that the tomato genome can be fractioned into three compartments with different gene and repeat density, each compartment presenting contrasting repeat and gene composition, repeat-gene associations and different gene transcriptional levels. In the context of fruit ripening, we found that repeats are present in the majority of differentially methylated regions (DMRs) and thousands of repeat-associated DMRs are found in gene proximity including hundreds that are differentially regulated. Furthermore, we found that repeats are also present in the proximity of binding sites of the key ripening protein RIN. We also observed that some repeat families are present at unexpected high frequency in the proximity of genes that are differentially expressed during tomato ripening.",
            "output": [
                "Does comprehensive repeatome annotation reveal strong potential impact of repetitive elements on tomato ripening?"
            ]
        },
        {
            "id": "task847-7ea3cf4e48d24813945912fac837150b",
            "input": "Malignant astrocytic gliomas are the most common and lethal brain malignancies due to their refractory to the current therapies. Nowadays, molecular targeted therapy has attracted great attention in treatment of glioma. Connexin 43 (Cx43) and micro ribonucleic acid-21(miR-21) are among molecules that are involved in glioma development and progression. These molecules showed potential to be as target molecules with regard to glioma. Some studies have reported that cyclic adenosine monophosphate (cAMP) signaling could be effective on Cx43 and miR-21 in tissues other than in brain. We investigate possible relationship between \u03b2-adrenergic receptor and its newly described downstream, exchange protein directly activated by cAMP (Epac) signaling pathway and expression of Cx43 and miR-21 in low (1321N1) and high grade (U87MG) glioma cell lines.', 'We treated cells with \u03b2-adrenergic agonist and Epac activator with and without adenyl cyclase inhibitor. Cx43 and miR-21 expression were measured with real-time PCR.', 'Our data showed that in 1321N1 cells, \u03b2-adrenergic-Epac pathway stimulation up and down-regulated Cx43 and miR-21 expression respectively. Whereas, in U87MG cells these interventions had no effect on Cx43 and miR-21 expression.",
            "output": [
                "Do cAMP-Epac Pathway Stimulation Modulate Connexin-43 and MicroRNA-21 Expression in Glioma Cells?"
            ]
        },
        {
            "id": "task847-1aee1d0ec55849a99007cdfe6f84fe9b",
            "input": "Habitat selection may have profound evolutionary consequences, but they strongly depend on the underlying preference mechanism, including genetically-determined, natal habitat and phenotype-dependent preferences. It is known that different mechanisms may operate at the same time, yet their relative contribution to population differentiation remains largely unexplored empirically mainly because of the difficulty of finding suitable study systems. Here, we investigate the role of early experience and genetic background in determining the outcome of settlement by pied flycatchers (Ficedula hypoleuca) breeding in two habitat patches between which dispersal and subsequent reproductive performance is influenced by phenotype (body size). For this, we conducted a cross-fostering experiment in a two-patch system: an oakwood and a conifer plantation separated by only 1\\xa0km.', \"Experimental birds mostly returned to breed in the forest patch where they were raised, whether it was that of their genetic or their foster parents, indicating that decisions on where to settle are determined by individuals' experience in their natal site, rather than by their genetic background. Nevertheless, nearly a third (27.6\\xa0%) moved away from the rearing habitat and, as previously observed in unmanipulated individuals, dispersal between habitats was phenotype-dependent. Pied flycatchers breeding in the oak and the pine forests are differentiated by body size, and analyses of genetic variation at microsatellite loci now provide evidence of subtle genetic differentiation between the two populations. This suggests that phenotype-dependent dispersal may contribute to population structure despite the short distance and widespread exchange of birds between the study plots.",
            "output": [
                "Does natal habitat imprinting counteract the diversifying effects of phenotype-dependent dispersal in a spatially structured population?"
            ]
        },
        {
            "id": "task847-fd0b4c18c36342d79d84c97880b3b04e",
            "input": "To determine the role of NOTCH during the arterial injury response and the subsequent chronic arterial-wall inflammation underlying atherosclerosis.', 'We have generated a mouse model of endothelial-specific (Cdh5-driven) depletion of the Notch effector recombination signal binding protein for immunoglobulin kappa J region (RBPJ) [(ApoE",
            "output": [
                "Does endothelial Jag1-RBPJ signalling promote inflammatory leucocyte recruitment and atherosclerosis?"
            ]
        },
        {
            "id": "task847-3f7cb79dbcfa410ab3352b9e046822ac",
            "input": "Material loss at the taper junction of metal-on-metal total hip arthroplasties has been implicated in their early failure. The mechanisms of material loss are not fully understood; analysis of the patterns of damage at the taper can help us better understand why material loss occurs at this junction.', 'We mapped the patterns of material loss in a series of 155 metal-on-metal total hip arthroplasties received at our center by scanning the taper surface using a roundness-measuring machine. We examined these material loss maps to develop a 5-tier classification system based on visual differences between different patterns. We correlated these patterns to surgical, implant, and patient factors known to be important for head-stem taper damage.', 'We found that 63 implants had \"minimal damage\" at the taper (material loss <1 mm",
            "output": [
                "Does damage Patterns at the Head-Stem Taper Junction help Understand the Mechanisms of Material Loss?"
            ]
        },
        {
            "id": "task847-07c6811630604deca5480b69e9caee1c",
            "input": "Although posttraumatic stress disorder (PTSD) and chronic pain frequently occur in tandem, the pathophysiological mechanisms mediating this comorbidity are poorly understood. Because excessive inflammation occurs in both conditions, we examined the cerebrospinal fluid (CSF) concentrations of inflammatory response mediators interleukin 1-beta (IL-1\u03b2), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF\u03b1) and interleukin 10 (IL-10) after prolonged suprathreshold pain stimulus in 21 male combat veterans; 10 with PTSD and 11 combat controls (CC).', 'After completing baseline quantitative sensory testing (QST) and psychological profiling, all patients received an injection of capsaicin into the quadriceps muscle. Spontaneously reported pain was measured for 30min after the capsaicin injection. The evoked pain measure of temporal summation was tested between 70 and 110min post capsaicin injection. Inflammatory (IL-1\u03b2, IL-6, IL-8 TNF\u03b1) and anti-inflammatory (IL-10) CSF cytokines were measured before (baseline) and after capsaicin injection over a time frame of 110min.', 'Following intramuscular capsaicin injection, pro-inflammatory cytokines [TNF\u03b1, IL-6, IL-8] significantly increased (percent rise from baseline) in both groups, whereas IL-1\u03b2 significantly increased in the PTSD group only. The anti-inflammatory cytokine IL-10 showed an immediate (within 10min) increase in the CC group; however, the IL-10 increase in the PTSD group was delayed and not consistently elevated until 70min post injection.",
            "output": [
                "Does posttraumatic stress disorder influence the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans?"
            ]
        },
        {
            "id": "task847-fe19cc3d3dd940f3b1980f8cf34cae8c",
            "input": "The EuroSCORE (European System for cardiac operative risk evaluation) stratifies cardiac risk surgery in easy and accessible manner; it was validated in North America with good results but in many countries of Latin America is used routinely without prior validation. Our objective was to validate the EuroSCORE in patients with cardiac valve surgery at the Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez (INCICh) in M\u00e9xico.', 'EuroSCORE additive and logistic models were used to predict mortality in adults undergoing cardiac valve surgery from march 2004 to march 2008. The goodness of fit test of Hosmer-Lemeshow was used to evaluate the calibration. The area under the ROC curve was calculated to determinate discrimination.', 'We included 1188 patients with ages of 51.3\u00b114.5 years, 52% women. There were significant differences in the prevalence of risk factors among the INCICh and the EuroSCORE populations. Total mortality was 9.68% versus 5% and 5.6% predicted by additive and logistic EuroSCORE. According to additive EuroSCORE the risk was low in 11.3%, intermediate in 52.9% and high in 35.9%; for these groups the mortality was .7%, 6.34% and 17.4% against those predicted of 2%, 3.9% and 7.64%. Hosmer-Lemeshow test had a P<.001 for both models and the area under the ROC curve was .707 and .694 for additive and logistic EuroSCORE.",
            "output": [
                "Do [ EuroSCORE underestimate the mortality risk in cardiac valve surgery of Mexican population ]?"
            ]
        },
        {
            "id": "task847-ec48749fa9274931ba9380419cd61289",
            "input": "Cancer pain is still inadequately treated in up to 60% of cancer patients. Based on the additional effect on the N-Methyl-d-Aspartate receptor, we expected that methadone (Met) could provide better pain relief than fentanyl (Fen) in cancer pain with a neuropathic pain component.', 'A randomised controlled trial was performed with 52 strong opioids naive patients with head-and-neck cancer with substantial pain (pain Numerical Rating Scale [NRS]\\xa0>\\xa04) and a neuropathic pain component (Douleur Neuropathique [DN4]\\xa0>\\xa04). Twenty-six patients were treated with Met and 26 with Fen. Patients were evaluated at 1, 3 and 5 weeks. The primary outcomes were reduction in average pain, clinical success (defined as 50% average pain decrease)\\xa0and reduction in pain interference. Secondary outcomes were global perceived effect (GPE) and side-effects.', 'Reduction in NRS was higher with the use of Met at 1, 3 and 5 weeks (pain change 2.9, 3.1 and 3.1) compared to Fen (1.4, 1.7 and 2.0). This difference was significant at 1 (p\\xa0=\\xa00.011) and at 3 weeks (p\\xa0=\\xa00.03). Clinical success (>50% improvement) was higher with Met at 1 week (15% versus 50%, p\\xa0=\\xa00.012). The change in pain interference, the GPE and side-effect profile were not significantly different between the groups.",
            "output": [
                "Is methadone superior to fentanyl in treating neuropathic pain in patients with head-and-neck cancer?"
            ]
        },
        {
            "id": "task847-97b7cebe22404be5a179c64ce2f18d69",
            "input": "Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive.",
            "output": [
                "Does targeting factor VIII expression to platelets for hemophilia A gene therapy induce an apparent thrombotic risk in mice?"
            ]
        },
        {
            "id": "task847-d2e36cf31db64edbaf6047cddaa94284",
            "input": "A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients with type 2 diabetes.', 'A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes patients; 58% men, mean\\u2009\u00b1\\u2009SD age 64\\u2009\u00b1\\u200911\\xa0years) was followed for a median of 6.0\\xa0years for death as primary endpoint and major adverse CV events (MACE; i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with end-stage renal disease, defined as a requirement for dialysis or a history of kidney transplantation, were excluded. Patients were grouped into quartiles according to ANGPTL2 concentrations at inclusion: <11.2 (Q1), 11.2-14.7 (Q2), 14.8-19.5 (Q3) or >19.5 (Q4) ng/ml.', 'During follow up, 367 patients (representing 4.5% of the total person-years) died and 290 patients (representing 3.7% of the total person-years) presented with MACE. Both the survival and MACE-free survival rates were significantly different between ANGPTL2 quartiles (logrank 82.12, p\\u2009<\\u20090.0001 for death; and logrank 65.14, p\\u2009<\\u20090.0001 for MACE). Patients with ANGPTL2 concentrations higher than 19.5\\xa0ng/ml (Q4) had a significantly higher risk of death and MACE than those with ANGPTL2 levels of 19.5\\xa0ng/ml or less (Q1-3) (HR for death 2.44 [95% CI 1.98, 3.00], p\\u2009<\\u20090.0001; HR for MACE 2.43 [95% CI 1.92, 3.06], p\\u2009<\\u20090.0001) after adjustment for sex, age and established CV risk factors. Using ANGPTL2 concentrations, prediction of the risk of mortality, as assessed by integrated discrimination improvement (IDI), was significantly improved (IDI 0.006\\u2009\u00b1\\u20090.002, p\\u2009=\\u20090.0002).",
            "output": [
                "Is aNGPTL2 associated with an increased risk of cardiovascular events and death in diabetic patients?"
            ]
        },
        {
            "id": "task847-46722ae2f0004d91b3103a4be72a44e1",
            "input": "We previously identified two ARDS subphenotypes in two separate randomized controlled trials, with differential response to positive end-expiratory pressure. The current analysis sought to identify these subphenotypes in a third ARDS cohort, to test whether subphenotypes respond differently to fluid management strategy, and to develop a practical model for subphenotype identification.', '\\xa0We used latent class analysis of baseline clinical and plasma biomarker data to identify subphenotypes in the Fluid and Catheter Treatment Trial (FACTT; n=1000). Logistic regression was used to test for an interaction between subphenotype and treatment for mortality. We used stepwise modeling to generate a model for subphenotype identification in FACTT and validated its accuracy in the two cohorts in which we previously identified ARDS subphenotypes.', 'We confirmed that a two-class (two-subphenotype) model best described the study population. Subphenotype 2 was again characterized by higher inflammatory biomarkers and hypotension. Fluid management strategy had significantly different effects on 90-day mortality in the two subphenotypes (p=0.0039 for interaction); mortality in Subphenotype 1 was 26% with fluid conservative strategy versus 18% with fluid liberal, while mortality in Subphenotype 2 was 40% with fluid conservative strategy versus 50% in fluid liberal. A three-variable model of interleukin-8, bicarbonate, and tumor necrosis factor receptor-1 accurately classified the subphenotypes.",
            "output": [
                "Do aRDS Subphenotypes Respond Differently to Randomized Fluid Management Strategy?"
            ]
        },
        {
            "id": "task847-78e866907ed048d295a746222c741d6a",
            "input": "Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA).\", 'Genotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed. A novel identified association was replicated further in 2 independent cohorts. We further examined the association of the identified single-nucleotide polymorphism with microbiota from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured using 16S sequencing.', 'We identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P\\xa0= 5.55\\xa0\u00d7 10(-13)). This variant has been associated previously with distinct phenotypes including obesity, lipid levels, blood pressure, and schizophrenia. We subsequently determined that the CD risk allele was associated with altered colonic mucosal microbiome composition in both healthy controls (P\\xa0= .009) and CD cases\\xa0(P\\xa0= .0009). Moreover, microbes depleted in healthy\\xa0carriers strongly overlap with those reduced in CD patients (P\\xa0=\\xa09.24\\xa0\u00d7 10(-16)) and overweight individuals (P\\xa0=\\xa06.73\\xa0\u00d7\\xa010(-16)).",
            "output": [
                "Does a Pleiotropic Missense Variant in SLC39A8 be Associated With Crohn 's Disease and Human Gut Microbiome Composition?"
            ]
        },
        {
            "id": "task847-bef8247012384221bde6e0f5ad17fa73",
            "input": "Preoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have prognostic value in patients with various operable tumors. The aim of our study was to determine whether NLR and PLR are predictive of survival in thymic carcinoma patients after complete resection.', 'A total of seventy-nine patients who underwent complete resection of thymic carcinoma at our hospital between January 2005 and December 2015 were retrospectively enrolled. Differential leukocyte counts were collected before surgery, and the relationships of NLR, PLR, and other patient clinical variables with survival were estimated by Cox regression analysis and Kaplan-Meier survival analysis.', 'Univariate analysis found that a high level of NLR was associated with lower disease-free survival (DFS) (HR: 3.385, 95% CI: 1.073-10.678, P=0.037) and lower overall survival (OS) (HR: 12.836, 95% CI: 1.615-101.990, P=0.016). The optimal NLR threshold of 4.1 could stratify the patients with high risk of recurrence or metastasis (P=0.026) and death (P=0.006). Meanwhile, the NLR value of >4.1 in those patients was associated with bigger tumor size (P=0.035) and more advanced Masaoka stages (P=0.040) compared with NLR \u22644.1. However, the PLR and other variables were not significantly associated with survival in thymic carcinoma patients.",
            "output": [
                "Is prognostic value of preoperative neutrophil-lymphocyte ratio superior to platelet-lymphocyte ratio for survival in patients who underwent complete resection of thymic carcinoma?"
            ]
        },
        {
            "id": "task847-bd639a4a5b044f51b64be336519c7323",
            "input": "Angiotensin II (AngII), a vasoconstrictive peptide of the renin-angiotensin system (RAS), promotes hepatic fibrogenesis and induces microRNA-21(mir-21) expression. Angiotensin-(1-7) [Ang-(1-7)] is a peptide of the RAS, which attenuates liver fibrosis. Recently, it was reported that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome participated in liver fibrosis. However, it remains unclear how mir-21 mediates AngII-induced NLRP3 inflammasome activation. We investigate the role of AngII-induced mir-21 in the regulation of NLRP3 inflammasome/IL-1\u03b2 axis in liver fibrosis.', 'In vivo, circulating mir-21 was upregulated in patients with liver fibrosis and was positively correlated with liver fibrosis and oxidation. Treatment with Ang-(1-7) inhibited mir-21, NLRP3 inflammasome, and liver fibrosis after bile duct ligation (BDL) or AngII infusion. Inhibition of mir-21 suppressed the Smad7/Smad2/3/NOX4, Spry1/ERK/NF-\u03baB pathway, NLRP3 inflammasome, and liver fibrosis induced by AngII infusion. In vitro, AngII upregulated mir-21 expression via targeting Smad7 and Spry1 in primary hepatic stellate cells (HSCs). In contrast, Ang-(1-7) suppressed mir-21 expression and oxidation induced by AngII. Overexpression of mir-21 promoted oxidation, and collagen production enhanced the effect of AngII on NLRP3 inflammasome activation via the Spry1/ERK/NF-\u03baB, Smad7/Smad2/3/NOX4 pathways. However, downregulation of mir-21 exerted the opposite effects.",
            "output": [
                "Does microRNA-21 mediate Angiotensin II-Induced Liver Fibrosis by Activating NLRP3 Inflammasome/IL-1\u03b2 Axis via Targeting Smad7 and Spry1?"
            ]
        },
        {
            "id": "task847-16aa36812dd440248fd08c58512fe6fb",
            "input": "Platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for orthopaedics and sports-related injuries, and various clinically available PRP preparation methods exist. However, the differences in PRP quality among numerous preparation methods remain unclear. Specifically, the benefit of including leukocytes in the PRP product remains controversial, and few studies have been conducted to evaluate the effects of the interaction between platelets and leukocytes on the growth factor concentrations. The aim of the present study was to compare the biological characteristics of PRPs focusing on the leukocyte concentration and composition.', 'Leucocyte rich (LR)-PRP, leucocyte poor (LP)-PRP, and pure-PRP were prepared from the peripheral blood of 6 healthy male volunteers (mean age: 31.3 years). The concentrations of platelets, leukocytes, erythrocytes, growth factors (transforming growth factor-beta 1: TGF-\u03b21; fibroblast growth factor-basic: FGF-b; platelet-derived growth factor-BB: PDGF-BB; vascular endothelial growth factor: VEGF) and matrix metalloproteinase-9 (MMP-9) from each of the PRP samples were measured. Considering the interaction between platelets and leukocytes, correlations between platelets/leukocytes and growth factors/MMP-9 were analyzed using partial correlation coefficients.', 'The platelet concentration did not differ among the three PRP preparation methods. Conversely, the leukocyte concentration was dramatically different: 14.9\\xa0\u00b1\\xa04.5 (10(3)/\u03bcl) in LR-PRP, 2.4\\xa0\u00b1\\xa01.3 (10(3)/\u03bcl) in LP-PRP, 0.2\\xa0\u00b1\\xa00.2 (10(3)/\u03bcl) in pure-PRP. The platelet concentration positively correlated with all growth factors. On the other hand, the leukocyte concentration positively correlated with PDGF-BB and the VEGF concentration, while it negatively correlated with FGF-b. Regarding catabolic factors, the MMP-9 concentration strongly correlated with the leukocyte concentration, while there was no correlation between the platelet and MMP-9 concentrations.",
            "output": [
                "Does leukocyte concentration and composition in platelet-rich plasma ( PRP ) influence the growth factor and protease concentrations?"
            ]
        },
        {
            "id": "task847-a0393d19c8ab4890804134daa7894381",
            "input": "Antibiotic resistance is a challenge in long-term care facilities (LTCFs). The objective of this study was to demonstrate that a novel, minimally invasive program not interfering with activities of daily living or socialization could lower methicillin-resistant Staphylococcus aureus (MRSA) disease.', 'This was a prospective, cluster-randomized, nonblinded trial initiated at 3 LTCFs. During year 1, units were stratified by type of care and randomized to intervention or control. In year 2, all units were converted to intervention consisting of universal decolonization using intranasal mupirocin and a chlorhexidine bath performed twice (2 decolonization-bathing cycles 1 month apart) at the start of the intervention period. Subsequently, after initial decolonization, all admissions were screened on site using real-time polymerase chain reaction, and those MRSA positive were decolonized, but not isolated. Units received annual instruction on hand hygiene. Enhanced bleach wipe cleaning of flat surfaces was done every 4 months.', 'There were 16,773 tests performed. The MRSA infection rate decreased 65% between baseline (44 infections during 365,809 patient days) and year 2 (12 infections during 287,847 patient days; P\\u2009<.001); a significant reduction was observed at each of the LTCFs (P\\u2009<.03).",
            "output": [
                "Is reduction of methicillin-resistant Staphylococcus aureus infection in long-term care possible while maintaining patient socialization : A prospective randomized clinical trial?"
            ]
        },
        {
            "id": "task847-bbac9de67b9d4e0087f1fff2de594bfb",
            "input": "Despite modern antiretroviral therapy, HIV-associated neuropathy is one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of distal neuropathic pain is not fully explained by the degree of peripheral nerve damage. A better understanding of brain structure in HIV distal neuropathic pain may help explain why some patients with HIV neuropathy report pain while the majority does not. Previously, we reported that more intense distal neuropathic pain was associated with smaller total cerebral cortical gray matter volumes. The objective of this study was to determine which parts of the cortex are smaller.', 'HIV positive individuals with and without distal neuropathic pain enrolled in the multisite (N\\u2009=\\u2009233) CNS HIV Antiretroviral Treatment Effects (CHARTER) study underwent structural brain magnetic resonance imaging. Voxel-based morphometry was used to investigate regional brain volumes in these structural brain images.', 'Left ventral posterior cingulate cortex was smaller for HIV positive individuals with versus without distal neuropathic pain (peak P\\u2009=\\u20090.017; peak t\\u2009=\\u20095.15; MNI coordinates x\\u2009=\\u2009-6, y\\u2009=\\u2009-54, z\\u2009=\\u200920). Regional brain volumes within cortical gray matter structures typically associated with pain processing were also smaller for HIV positive individuals having higher intensity ratings of distal neuropathic pain.",
            "output": [
                "Does hIV Distal Neuropathic Pain be Associated with Smaller Ventral Posterior Cingulate Cortex?"
            ]
        },
        {
            "id": "task847-d1dbd14b3ee340f89ac317422c427851",
            "input": "The Muscle-specific RING-finger (MuRF) protein family of E3 ubiquitin ligases is important for maintenance of muscular structure and function. MuRF proteins mediate adaptation of striated muscles to stress. MuRF2 and MuRF3 bind to microtubules and are implicated in sarcomere formation with noticeable functional redundancy. However, if this redundancy is important for muscle function in vivo is unknown. Our objective was to investigate cooperative function of MuRF2 and MuRF3 in the skeletal muscle and the heart in vivo.', 'MuRF2 and MuRF3 double knockout mice (DKO) were generated and phenotypically characterized. Skeletal muscle and the heart were investigated by morphological measurements, histological analyses, electron microscopy, immunoblotting, and real-time PCR. Isolated muscles were subjected to in vitro force measurements. Cardiac function was determined by echocardiography and working heart preparations. Function of cardiomyocytes was measured in vitro. Cell culture experiments and mass-spectrometry were used for mechanistic analyses.', 'DKO mice showed a protein aggregate myopathy in skeletal muscle. Maximal force development was reduced in DKO soleus and extensor digitorum longus. Additionally, a fibre type shift towards slow/type I fibres occurred in DKO soleus and extensor digitorum longus. MuRF2 and MuRF3-deficient hearts showed decreased systolic and diastolic function. Further analyses revealed an increased expression of the myosin heavy chain isoform beta/slow and disturbed calcium handling as potential causes for the phenotype in DKO hearts.",
            "output": [
                "Do muscle RING-finger 2 and 3 maintain striated-muscle structure and function?"
            ]
        },
        {
            "id": "task847-1ca0f6dbdbed422db3ce3c0f68e83551",
            "input": "Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited.', 'We combined neuroanatomic, pharmacologic, electrophysiological, Cre-lox, and chemogenetic approaches to investigate the functions of 5-hydroxytryptamine (5-HT) 2C receptor (5-HT', 'We showed that 5-HT stimulates DA neural activity through a 5-HT",
            "output": [
                "Does activation of Serotonin 2C Receptors in Dopamine Neurons inhibit Binge-like Eating in Mice?"
            ]
        },
        {
            "id": "task847-9463a93f4d8349be930da431c4c20240",
            "input": "Transannular patching (TAP) frequently accompanies primary repairs (PRs) in symptomatic neonates with tetralogy of Fallot (TOF). If a systemic-pulmonary shunt (SPS) facilitates the growth of the pulmonary valve annulus (PVA), patients with a marginally small PVA could benefit from a staged repair in terms of lowering the risk of TAP.', 'Among 216 infants with TOF who underwent surgical intervention between January 2004 and December 2013, 29 infants underwent SPS with a subsequent repair (SPS group), whereas 187 infants received a PR (PR group). Median age and the Z-score of the PVA (PVA [Z]) at SPS were 32 days and\\xa0-3.5, respectively. There was one late death and one follow-up loss after SPS, and preservation of the PVA was achieved on repair in 16 patients (16 of 29; 55%).', 'Multiple regression analysis showed that performance of SPS was the only indicator of the increase in the PVA (Z) in the entire cohort (n\\xa0= 216). On mixed linear regression, the PVA (Z) increased significantly after the placement of an SPS (-3.6\\xa0+ 0.2*duration in months, p\\xa0= 0.001), whereas the prerepair changes in the PVA (Z) were not statistically significant in the PR group (p\\xa0= 0.7), with a significant intergroup difference (p < 0.001). Receiver operating characteristic curve analysis showed that placement of TAP is expected when the preshunt PVA (Z) is smaller than\\xa0-4.2 (area under the curve: 0.82; 95% confidence interval: 0.62 to 1.00; sensitivity, 100%; specificity, 73%).",
            "output": [
                "Does systemic-Pulmonary Shunt facilitate the Growth of the Pulmonary Valve Annulus in Patients With Tetralogy of Fallot?"
            ]
        },
        {
            "id": "task847-180bf0470d864b70a6d7cd1d48ba18a1",
            "input": "To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterec\u00actomy (RNU).', 'We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent di\u00acagnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multi\u00acvariate analyses were used to determine the independent risk factors.', 'The median follow-up time was 48 months (interquartile range (IQR): 31- 77 months). Patients who underwent ureteroscopy were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality (p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative ureteroscopy have a statistically significant better 2-year (79.3%\u00b10.02 versus 71.4%\u00b10.02, p<0.001) and 5-year intravesical recurrence-free survival rates (64.9%\u00b10.05 versus 44.3%\u00b10.06, p<0.001) than patients who un\u00acderwent ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006), multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0 stage tumor (p=0.045) were independent predictors of IVR.",
            "output": [
                "Is diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma Independently Associated with Intravesical Recurrence after Radical Nephroureterectomy?"
            ]
        },
        {
            "id": "task847-e030f19c6ac94116ba487c020b845ec6",
            "input": "Lung adenocarcinomas with mutations in the epidermal growth factor receptor (EGFR) have unprecedented initial responses to targeted therapy against the EGFR. Over time, however, these tumors invariably develop resistance to these drugs. We set out to investigate alternative treatment approaches for these tumors.', 'To investigate the immunologic underpinnings of EGFR mutant lung adenocarcinoma, we utilized a bi-transgenic mouse model in which a mutant human EGFR gene is selectively expressed in the lungs.', 'EGFR oncogene-dependent progression and remission of lung adenocarcinoma was respectively dependent upon the expansion and contraction of alveolar macrophages, and the mechanism underlying macrophage expansion was local proliferation. In tumor-bearing mice, alveolar macrophages downregulated surface expression of MHC-II and costimulatory molecules; increased production of CXCL1, CXCL2, IL-1RA; and increased phagocytosis. Depletion of alveolar macrophages in tumor-bearing mice resulted in reduction of tumor burden, indicating a critical role for these cells in the development of EGFR mutant adenocarcinoma. Treatment of mice with EGFR targeting clinical drugs (erlotinib and cetuximab) resulted in a significant decrease in alveolar macrophages in these mice. An activated alveolar macrophage mRNA signature was dominant in human EGFR mutant lung adenocarcinomas, and the presence of this alveolar macrophage activation signature was associated with unfavorable survival among patients undergoing resection for EGFR mutant lung adenocarcinoma.",
            "output": [
                "Is progression of EGFR mutant lung adenocarcinoma driven by alveolar macrophages?"
            ]
        },
        {
            "id": "task847-cca72085b69e46b19d8aa5187fa0311a",
            "input": "Excessive time between the first presentation of symptoms of pulmonary tuberculosis (PTB) and diagnosis contributes to ongoing transmission and increased risk of infection in the community, as well as to increased disease severity and higher mortality. People with type 2 diabetes mellitus (T2DM) have a higher risk of developing PTB. However, the effect of T2DM on delayed diagnosis of PTB is not fully understood. This study investigated the effects of hyperglycemia (diabetes and prediabetes) and other factors on PTB patient delay in a rural area of China.', 'In the present community-based investigation, PTB patients aged \u226516\\u2009years newly diagnosed at county tuberculosis dispensaries were recruited consecutively between September 2011 and December 2013. Fasting blood glucose was determined in all subjects, and a structured questionnaire was used to collect basic information.', 'Of the 2280 patients, 605 (26.5\\xa0%) had hyperglycemia. The median (interquartile range) time to seeking health care was 44 (59) days. Health care seeking was delayed in 1754 subjects, and hyperglycemia was independently associated with an increased probability (odds ratio 2.10; 95\\xa0% confidence interval 1.49-2.97) of patient delay in subjects aged \u226530\\u2009years. Other factors associated with patient delay were cough, night sweats, and lack of knowledge regarding typical tuberculosis symptoms. The onset of hemoptysis was negatively correlated with patient delay.",
            "output": [
                "Is hyperglycemia associated with increased risk of patient delay in pulmonary tuberculosis in rural areas?"
            ]
        },
        {
            "id": "task847-a5c26a3e11b74f9e8a5bd108a897320a",
            "input": "Invasive infections caused by KPC-producing Klebsiella pneumoniae (KPCKP) are associated with very high mortality. Because infection is usually preceded by rectal colonization, we investigated if decolonization therapy (DT) with aminoglycosides had a protective effect in selected patients.', 'Patients with rectal colonization by colistin-resistant KPCKP who were at high risk of developing infection (because of neutropenia, surgery, previous recurrent KPCKP infections or multiple comorbidities) were followed for 180 days. Cox regression analysis including a propensity score was used to investigate the impact of the use of two intestinal decolonization regimens with oral aminoglycosides (gentamicin and neomycin/streptomycin) on mortality, risk of KPCKP infections and microbiological success. The study was registered with ClinicalTrials.gov (NCT02604849).', 'The study sample comprised 77 colonized patients, of which 44 (57.1%) received DT. At 180 days of follow-up, decolonization was associated with a lower risk of mortality in multivariate analyses (HR 0.18; 95% CI 0.06-0.55) and a lower risk of KPCKP infections (HR 0.14; 95% CI 0.02-0.83) and increased microbiological success (HR 4.06; 95% CI 1.06-15.6). Specifically, gentamicin oral therapy was associated with a lower risk of crude mortality (HR 0.15; 95% CI 0.04-0.54), a lower risk of KPCKP infections (HR 0.86; 95% CI 0.008-0.94) and increased microbiological response at 180 days of follow-up (HR 5.67; 95% CI 1.33-24.1). Neomycin/streptomycin therapy was only associated with a lower risk of crude mortality (HR 0.22; 95% CI 0.06-0.9).",
            "output": [
                "Is oral decontamination with aminoglycosides associated with lower risk of mortality and infections in high-risk patients colonized with colistin-resistant , KPC-producing Klebsiella pneumoniae?"
            ]
        },
        {
            "id": "task847-76e8c9ba91b2475ba206e9a264b8c964",
            "input": "Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM.', 'Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated diabetes to probe mechanisms.', 'Mst1 knockout alleviated while Mst1 overexpression aggravated cardiac dysfunction in diabetes. Diabetic Mst1 transgenic mice exhibited decreased LC3 expression and enhanced protein aggregation. In contrast, typical autophagosomes were observed in diabetic Mst1-knockout mice with increased LC3 expression and reduced protein aggregation. Mst1 downregulation promoted autophagic flux as demonstrated by increased LC3-II and decreased p62 expression in the presence of bafilomycin A1. Furthermore, Mst1 overexpression increased, while Mst1 knockout decreased, cardiomyocyte apoptosis both in vivo and in vitro. Co-immunoprecipitation assays showed that Mst1 overexpression promoted Beclin1 binding to B cell lymphoma 2 (Bcl-2) and induced dissociation of Bcl-2 from Bax in diabetic mice. Conversely, Mst1 knockout disrupted the Beclin1-Bcl-2 complex and enhanced the interaction between Bcl-2 and Bax.",
            "output": [
                "Does mST1 coordinately regulate autophagy and apoptosis in diabetic cardiomyopathy in mice?"
            ]
        },
        {
            "id": "task847-2798b4e0321c464abd537e052114d02d",
            "input": "To explore the effects of sulforaphane (SFN) on neuronal apoptosis in hippocampus and memory impairment in diabetic rats.', 'Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group). Streptozotocin (STZ) was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1) were detected by western blotting. Neurotrophic factor levels and AKT/GSK3\u03b2 pathway were also detected.', 'Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3\u03b2, NGF and BDNF expressions.",
            "output": [
                "Does sulforaphane prevent Neuronal Apoptosis and Memory Impairment in Diabetic Rats?"
            ]
        },
        {
            "id": "task847-afab0b54065647959d966d0e3a672181",
            "input": "Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs.', 'To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-x03BA;B in the prefrontal cortex of neonatal pigs.', 'Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5 h after hypoxia. Samples of prefrontal cortex and plasma were analyzed.', 'Cortex: there was no significant difference in mRNA expression between the intervention groups regarding IL-1\u03b2, IL6, TNF\u03b1, MMP2, MMP9 or IL18. Pigs exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a significantly lower protein concentration of IL-1\u03b2 than pigs treated with saline (placebo controls), i.e. 8.8 \u00b1 3.9 versus 16.8 \u00b1 10.5 pg/mg protein (p = 0.02). The activation of the transcription factor NF-x03BA;B (measured as the fold-change of phosphorylated p65Ser 536), was reduced in the NACA-pigs when compared to the placebo controls (5.2 \u00b1 4.3 vs. 16.0 \u00b1 13.5; p = 0.02). No difference between the intervention groups regarding brain histopathology or in the levels of 8-oxoguanine measured in the prefrontal cortex were observed. Plasma: the NACA-pigs had a stronger reduction of TNF\u03b1 in the first 30 min following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24 (14-32)% (p = 0.01).",
            "output": [
                "Does n-Acetylcysteine Amide exert Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia?"
            ]
        },
        {
            "id": "task847-7a0ba99bda6a4167bf43a3970b0678ca",
            "input": "Prospective cohort.', 'Elbow stiffness is the most common adverse event after isolated radial head fractures.', 'To assess the effect of coaching on elbow motion during the same office visit in patients with such fractures.', 'We enrolled 49 adult patients with minimally displaced radial head fractures, within 14 days of injury. After diagnosis, we measured demographics, catastrophic thinking, health anxiety, symptoms of depression, upper extremity-specific symptoms and disability, pain, and elbow and wrist motion. The patient was taught to apply an effective stretch in spite of the pain to limit stiffness, and elbow motion was measured again.', 'With the exception of radial deviation and pronation, motion measures improved slightly but significantly on average immediately after coaching. Elbow flexion improved from 79% (110\u00b0 \u00b1 22\u00b0) of the uninjured side to 88% (122\u00b0 \u00b1 18\u00b0) after coaching (P\\xa0<\\xa0.001); elbow extension improved from 71% (29\u00b0 \u00b1 14\u00b0) to 78% (22\u00b0 \u00b1 15\u00b0) (P\\xa0=\\xa0.0012).",
            "output": [
                "Does coaching of patients with an isolated minimally displaced fracture of the radial head immediately increase range of motion?"
            ]
        },
        {
            "id": "task847-38b87fd236ad4a6cb9c0f6b9f354631f",
            "input": "Whether higher penile human papillomavirus (HPV) viral load is associated with a lower rate of HPV clearance remains unknown.', 'We examined the association between penile HPV16 and HPV18 viral load and subsequent HPV clearance in uncircumcised Kenyan men.', 'Participants were human immunodeficiency virus (HIV)-seronegative, sexually active, 18- to 24-year-old men randomized to the control arm of a male circumcision trial in Kisumu, Kenya. Men provided exfoliated penile cells from two anatomical sites (glans/coronal sulcus and shaft) every 6 months for 2 years. GP5+/6+ polymerase chain reaction was used to identify 44 HPV-DNA types. Human papillomavirus viral load testing was conducted using a LightCyler real-time polymerase chain reaction assay; viral load was classified as high (>250 copies/scrape) or low (\u2264250 copies/scrape), for nonquantifiable values. The Kaplan-Meier method and Cox regression modeling were used to examine the association between HPV viral load and HPV clearance.', 'A total of 1097 men, with 291 HPV16 and 131 HPV18 cumulative infections over 24 months were analyzed. Human papillomavirus clearance at 6 months after first HPV detection was lower for high versus low viral load HPV16 infections in the glans (adjusted hazard ratio [aHR], 0.65; 95% confidence interval [CI], 0.46-0.92)] and shaft (aHR, 0.44; 95% CI, 0.16-0.90), and HPV18 infections in the glans (aHR, 0.05; 95% CI, 0.01-0.17).",
            "output": [
                "Do higher HPV16 and HPV18 Penile Viral Loads Are Associated With Decreased Human Papillomavirus Clearance in Uncircumcised Kenyan Men?"
            ]
        },
        {
            "id": "task847-35d71095d4a74bb39049d3ad06f58922",
            "input": "A previous systematic review showed that atraumatic restorative treatment (ART) can be an option to restore the occlusoproximal cavities in primary teeth; however, few studies fulfilled the criteria of inclusion to generate a high level of evidence.', 'To update the existing systematic review and address questions regarding survival rate of ART restorations compared to the conventional approach in occlusoproximal cavities in primary molars.', 'The search was extended beyond the original search through the PubMed/MEDLINE database up to February 2016. Furthermore, Web of Science and EMBASE were searched. The inclusion criteria were subjects related to the scope of the systematic review. After selection by title and abstract, potentially eligible articles were read in full and included in accordance with exclusion criteria. Meta-analysis was carried out with the outcome being the survival rate of restorations.', 'The search strategy identified 560 potentially relevant studies, in addition to 127 from the original systematic review. A total of four articles were included in the qualitative and quantitative analyses. Meta-analysis showed no statistically significant difference between ART and conventional approaches in survival rate of occlusoproximal cavities (OR = 0.887, 95% CI: 0.574-1.371).",
            "output": [
                "Is aRT an alternative for restoring occlusoproximal cavities in primary teeth - evidence from an updated systematic review and meta-analysis?"
            ]
        },
        {
            "id": "task847-0ccdf83bb5ac41b591ffb6642aa1fe7e",
            "input": "Telomerase Reverse Transcriptase (TERT) promoter mutation has been reported to be associated with aggressive characteristics in differentiated thyroid cancer (DTC). This study examined the status of TERT promoter mutation in distant metastatic DTC (DM-DTC), and evaluated the correlation between TERT mutation and radioactive iodine-131(RAI) uptake, as well as that between TERT mutation and therapy response.', 'TERT promoter and B-Raf proto-oncogene (BRAF) V600E mutation were retrospectively examined in primary tumors of 66 DM-DTC patients. Stimulated thyroglobulin (sTg) changes, RAI uptake status (avid or non-avid), and other imaging evidence were analyzed to evaluate therapy response. After a median follow-up of 46.5 months (interquartile range, 29.0 to 70.5 months), therapy response was classified as disease control and refractory.', \"The prevalence of TERT mutations was 22.73% (15/66), of which C228T mutation was more prevalent (13/15) than C250T mutation (2/15). Rising sTg was noticed in 93.33% (14/15) of TERT mutation group. While in cases with both mutations negative, 78.12 % (25/32) presented with decreased sTg. TERT mutation closely correlated with poor RAI therapy response (p\uff1c0.001), and all 15 patients were classified as refractory to RAI with a positive predictive value of 100% at the end point of follow-up. TERT mutation was associated with older mean age at diagnosis (p\uff1c0.001), larger mean tumor diameter (P = 0.013), and more likelihood of both BRAF mutation coexistence (P = 0.044) and refractory to RAI (p\uff1c0.001). In the 36 cases received imaging semi-quantitative analysis, it was found that TERT mutation significantly correlated with non-RAI-avidity, with a much lower mean tumor/background (T/B) ratio (obtained from post RAI therapy whole-body scanning) than TERT wild-type (p\uff1c0.001). And DM-DTC patients with TERT mutation were more likely to lose RAI-avidity at initial RAI therapy than those with only BRAF mutation (8/8 vs 5/11, Fisher's exact test, P = 0.018).",
            "output": [
                "Does tERT promoter mutation predict radioiodine refractory in distant metastatic differentiated thyroid cancer?"
            ]
        },
        {
            "id": "task847-fde87abc337c4849b26cd7d981d57d61",
            "input": "To assess the reliability of thyroglobulin (Tg) as a marker of iodine status during pregnancy.', '299 women aged 30.5 \u00b1 4.8 years (mean \u00b1 SD) were studied.', 'In every subject, we measured urinary iodine concentration (UIC), serum thyrotropin (TSH), Tg, free thyroxine (fT4), Tg autoantibodies (TgAbs) and human chorionic gonadotropin (hCG) levels. We excluded samples with increased TgAbs from the analysis.', 'According to WHO criteria, the study population was iodine deficient in every trimester. Serum Tg levels did not differ during the three trimesters of pregnancy. Serum hCG levels fell significantly as pregnancies advanced. A weak, significantly negative correlation (limited to the 3rd trimester) was found between Tg and UIC (\u03c1 = -0.187, p = 0.039). Serum fT4 decreased as pregnancies advanced and TSH increased. Serum fT4 was negatively correlated with TSH (\u03c1 = -0.161, p = 0.006) and positively with hCG (\u03c1 = +0.165, p = 0.005). The multiple regression equation of Tg based on hCG, TSH, UIC and trimester of pregnancy was significant but weak (F = 4.057, p = 0.003; R(2) = 0.055), with hCG as a significant predictor Tg (p for log hCG = 0.041).",
            "output": [
                "Does serum Thyroglobulin Concentration be a Weak Marker of Iodine Status in a Pregnant Population with Iodine Deficiency?"
            ]
        },
        {
            "id": "task847-759db1000dcf47c3843c4e0afce0ae98",
            "input": "Thyroid cancer is the most common endocrine gland malignancy. Advances in understanding the genetic basis for thyroid cancer revealed the potential involvement of several genes in the formation of thyroid tumors. Mutations in the gene coding for succinate dehydrogenase subtype B (SDHB) have been implicated in papillary thyroid cancer (PTC). Succinate dehydrogenase (SDH) is a heterotetrameric protein composed of four subunits, SDHA, SDHB, SDHC, and SDHD, and participates in both the electron transport chain and the tricarboxylic acid cycle. The aim of the study was to evaluate the association between variants in the SDHA, SDHB, SDHC, and SDHD genes and familiar PTC in a large Brazilian family.', 'Four patients with PTC, 1 patient with PTC and gastrointestinal stromal tumor (GIST), 1 patient with GIST, and their relatives - several of them with different thyroid problems - from a large Brazilian family were screened for genetic variations of SDHx genes with the use of polymerase chain reaction-single-stranded conformational polymorphism and direct sequencing.', 'Only one rare variation in SDHA was found in some of the family members, but not segregating with the disease. No other genetic variants of these genes were detected in the family members that presented with PTC and/or GIST.",
            "output": [
                "Is familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Associated with Succinate Dehydrogenase Defects?"
            ]
        },
        {
            "id": "task847-299bfedde12d41b6a297ddaf488d61f3",
            "input": "Valve interstitial cells are active and aggressive players in aortic valve calcification, but their dynamic mediation of mechanically-induced calcific remodeling is not well understood. The goal of this study was to elucidate the feedback loop between valve interstitial cell and calcification mechanics using a novel three-dimensional culture system that allows investigation of the active interplay between cells, disease, and the mechanical valve environment.', 'We designed and characterized a novel bioreactor system for quantifying aortic valve interstitial cell contractility in 3-D hydrogels in control and osteogenic conditions over 14 days. Interstitial cells demonstrated a marked ability to exert contractile force on their environment and to align collagen fibers with the direction of tension. Osteogenic environment disrupted interstitial cell contractility and led to disorganization of the collagen matrix, concurrent with increased \u03b1SMA, TGF-\u03b2, Runx2 and calcific nodule formation. Interestingly, RhoA was also increased in osteogenic condition, pointing to an aberrant hyperactivation of valve interstitial cells mechanical activity in disease. This was confirmed by inhibition of RhoA experiments. Inhibition of RhoA concurrent with osteogenic treatment reduced pro-osteogenic signaling and calcific nodule formation. Time-course correlation analysis indicated a significant correlation between interstitial cell remodeling of collagen fibers and calcification events.",
            "output": [
                "Does valve interstitial cell tensional homeostasis direct calcification and extracellular matrix remodeling processes via RhoA signaling?"
            ]
        },
        {
            "id": "task847-c9cdfe6a95fe4e9f8086008a1fc531c0",
            "input": "To verify the effects of several 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives on LPS-induced NO production, cellular ROS levels and cytokine expression in BV-2 microglial cells.', 'An MTT assay and FACS flow cytometry were performed to assess the cellular viability and apoptosis and cellular ROS levels, respectively. To examine the expression of pro-inflammatory cytokines and cellular signaling pathways, semi-quantitative RT-PCR and Western blotting were also used in this study.', 'Among the six newly synthesized DMNQ derivatives, 2-cyclohexylamino-5,8-dimethoxy-1,4-naphthoquinone (R6) significantly inhibited the NO production, cellular ROS levels and the cytokines expression in BV-2 microglial cells, which stimulated by LPS. Signaling study showed that compound R6 treatment also significantly down-regulated the LPS-induced phosphorylation of MAPKs (ERK, JNK and p38) and decreased the degradation of I\u03baB-\u03b1 in BV2 microglial cells.",
            "output": [
                "Does 2-cyclohexylamino-5,8-dimethoxy-1,4-naphthoquinone inhibit LPS-induced BV2 microglial activation through MAPK/NF-kB signaling pathways?"
            ]
        },
        {
            "id": "task847-fcacc51b9b72435cb750712094bf95a2",
            "input": "To investigate the surgical results of macular hole surgery without gas tamponade or postoperative posturing in patients with Stage 3 and Stage 4 macular holes with \u2265500 \u03bcm mean base diameter.', 'Retrospective interventional case series.', 'Twenty-six patients with Stage 3 and Stage 4 macular holes.', 'Twenty-six eyes of 26 patients with Stage 3 and Stage 4 macular holes and a mean base diameter of 892.8 \u00b1 349 \u03bcm underwent pars plana 23-gauge vitrectomy with broad internal limiting membrane peel (ILM peel), inverted ILM flap repositioning (ILMR), and use of autologous gluconated blood clumps as a macular plug to close the macular hole. No fluid-air exchange, endotamponade, or postoperative posturing was used. The subjects were followed up for 12 months. The anatomical outcome of the procedure was evaluated by fundus examination and optical coherence tomography. Spectral domain optical coherence tomography was used to study the restoration of the outer retinal layer integrity in the postoperative period. The preoperative and postoperative best-corrected visual acuities in logMAR units were compared to evaluate functional outcome.', 'Macular hole closure and best-corrected visual acuity before and after surgery.', 'Twenty-six patients with mean age 62.8 \u00b1 7.3 years, preoperative median best-corrected visual acuity 6/60 (1.0 logMAR units), and a mean base diameter of 892.8 \u00b1 349 \u03bcm underwent surgery to close macular holes without gas tamponade or postoperative posturing. Twenty patients (76.9%) were phakic. Twenty eyes (76.92%) had Stage 3 macular holes and 6 eyes (23.10%) had Stage 4 macular holes. After a single surgery, hole closure was achieved in 100% of eyes. The median best-corrected visual acuity improved from 6/60 (1.0 logMAR units) to 6/18 (0.50 logMAR units) (P < 0.001). Three patients needed cataract surgery at 12-month follow-up. No major intraoperative or postoperative complications were observed.",
            "output": [
                "Does cLOSING MACULAR hole WITH `` MACULAR PLUG '' WITHOUT GAS TAMPONADE AND POSTOPERATIVE POSTURING?"
            ]
        },
        {
            "id": "task847-afd0dbe0d4af438b818b798749a32161",
            "input": "Obese individuals are known to have increased Matrix metalloproteinase (MMP)-9 plasma levels and MMP-9 is reported to play an important role in obesity-associated adipose tissue inflammation. Since in obesity, the levels of circulatory saturated free fatty acid (FFA) palmitate (palimitic acid) are increased and modulate the expression of inflammatory mediators, the role of palmitate in the regulation of MMP-9 remains unclear.', 'Human monocytic cell line THP-1 and primary monocytes were stimulated with palmitate and TNF-\u03b1 (positive control). MMP-9 expression was assessed with real time RT-PCR and ELISA. Signaling pathways were studied by using THP-1-XBlue\u2122 cells, THP-1-XBlue\u2122-defMyD cells, anti-TLR4 mAb and TLR4 siRNA. Phosphorylation of NF-kB and c-Jun was analyzed by Western blotting.', 'Here, we provide the evidence that palmitate induces MMP-9 expression at both mRNA (THP-1: 6.8 \u00b1 1.2 Fold; P = 0.01; Primary monocytes: 5.9 \u00b1 0.7 Fold; P = 0.0003) and protein (THP1: 1116 \u00b114 pg/ml; P<0.001; Primary monocytes: 1426 \u00b1 13.8; P = 0.0005) levels in human monocytic cells. Palmitate-induced MMP-9 secretion was markedly suppressed by neutralizing anti-TLR-4 antibody (P < 0.05). Furthermore, genetic silencing of TLR4 by siRNA also significantly abrogated the palmitate-induced up-regulation of MMP-9. Additionally, MyD88-/- THP-1 cells did not express MMP-9 in response to palmitate treatment. Increased NF-\u03baB/AP-1 activity (P<0.05) was also observed in palmitate-treated THP-1 cells.",
            "output": [
                "Is palmitate-Induced MMP-9 Expression in the Human Monocytic Cells Mediated through the TLR4-MyD88 Dependent Mechanism?"
            ]
        },
        {
            "id": "task847-87c997b60fbb4592bcba69b2cebe8f60",
            "input": "Given evidence from genetic studies, we hypothesized that there may be a shared component to the role of myeloid function in Parkinson and Alzheimer disease (PD and AD) and assessed whether PD susceptibility variants influenced protein expression of well-established AD-associated myeloid genes in human monocytes.', 'We repurposed data in which AD-related myeloid proteins CD33, TREM1, TREM2, TREML2, TYROBP, and PTK2B were measured by flow cytometry in monocytes from 176 participants of the PhenoGenetic Project (PGP) and Harvard Aging Brain Study. Linear regression was used to identify associations between 24 PD risk variants and protein expression. The 2 cohorts were meta-analyzed in a discovery analysis, and the 4 most strongly suggestive results were validated in an independent cohort of 50 PGP participants.', 'We discovered and validated an association between the PD risk allele rs12456492(G) in the RIT2 locus and increased CD33 expression (p joint = 3.50 \u00d7 10(-5)) and found strongly suggestive evidence that rs11060180(A) in the CCDC62/HIP1R locus decreased PTK2B expression (p joint = 1.12 \u00d7 10(-4)). Furthermore, in older individuals, increased CD33 expression on peripheral monocytes was associated with a greater burden of parkinsonism (p = 0.047), particularly bradykinesia (p = 6.64 \u00d7 10(-3)).",
            "output": [
                "Does trans-pQTL study identify immune crosstalk between Parkinson and Alzheimer loci?"
            ]
        },
        {
            "id": "task847-fc0a6a7d38ac4929b9214efb9264ba99",
            "input": "The lung is exposed to airborne fungal spores, and fungi that colonize the oral cavity such as Candida albicans, but does not develop disease to opportunistic fungal pathogens unless the immune system is compromised. The Group IVA cytosolic phospholipase A2 (cPLA2\u03b1) is activated in response to Candida albicans infection resulting in the release of arachidonic acid for eicosanoid production. Although eicosanoids such as prostaglandins and leukotrienes modulate inflammation and immune responses, the role of cPLA2\u03b1 and eicosanoids in regulating C. albicans lung infection is not understood.', 'The responses of cPLA2\u03b1(+/+) and cPLA2\u03b1(-/-) Balb/c mice to intratracheal instillation of C. albicans were compared. After challenge, we evaluated weight loss, organ fungal burden, and the recruitment of cells and the levels of cytokines and eicosanoids in bronchoalveolar lavage fluid. The ability of macrophages and neutrophils from cPLA2\u03b1(+/+) and cPLA2\u03b1(-/-) mice to recognize and kill C. albicans was also compared.', 'After C. albicans instillation, cPLA2\u03b1(+/+) mice recovered a modest weight loss by 48\\xa0h and completely cleared fungi from the lung by 12\\xa0h with no dissemination to the kidneys. In cPLA2\u03b1(-/-) mice, weight loss continued for 72\\xa0h, C. albicans was not completely cleared from the lung and disseminated to the kidneys. cPLA2\u03b1(-/-) mice exhibited greater signs of inflammation including higher neutrophil influx, and elevated levels of albumin and pro-inflammatory cytokines/chemokines (IL1\u03b1, IL1\u03b2, TNF\u03b1, IL6, CSF2, CXCL1, CCL20) in bronchoalveolar lavage fluid. The amounts of cysteinyl leukotrienes, thromboxane B2 and prostaglandin E2 were significantly lower in bronchoalveolar lavage fluid from C. albicans-infected cPLA2\u03b1(-/-) mice compared to cPLA2\u03b1(+/+) mice. Alveolar macrophages and neutrophils from uninfected cPLA2\u03b1(-/-) mice exhibited less killing of C. albicans in vitro than cells from cPLA2\u03b1(+/+) mice. In addition alveolar macrophages from cPLA2\u03b1(-/-) mice isolated 6\\xa0h after instillation of GFP-C. albicans contained fewer internalized fungi than cPLA2\u03b1(+/+) macrophages.",
            "output": [
                "Does cytosolic phospholipase A2 contribute to innate immune defense against Candida albicans lung infection?"
            ]
        },
        {
            "id": "task847-a972031fd872421ea9f9b1aa70a37499",
            "input": "Much research effort has been focused on investigating new compounds derived from low-cost sources, such as natural products, for treating leishmaniasis. Oleuropein derived from numerous plants, particularly from the olive tree, Olea europaea L. (Oleaceae), is a biophenol with many biological activities. Our previous findings showed that oleuropein exhibits leishmanicidal effects against three Leishmania spp. in vitro, and minimizes the parasite burden in L. donovani-infected BALB/c mice. The aim of the present study is to investigate the possible mechanism(s) that mediate this leishmanicidal activity.', 'We determined the efficacy of oleuropein in elevating ROS and NO production in L. donovani-infected J774A.1 macrophages and in explanted splenocytes and hepatocytes obtained from L. donovani-infected BALB/c mice. We also assessed the expression of genes that are related to inflammation, T-cell polarization and antioxidant defense, in splenocytes. Finally, we determined the ratios of specific IgG2a/IgG1 antibodies and DTH reactions in L. donovani-infected BALB/c mice treated with oleuropein.', \"Oleuropein was able to elevate ROS production in both in vitro and in vivo models of visceral leishmaniasis and raised NO production in ex vivo cultures of splenocytes and hepatocytes. The extensive oxidative stress found in oleuropein-treated mice was obviated by the upregulation of the host's antioxidant enzyme (mGCLC) and the simultaneous downregulation of the corresponding enzyme of the parasite (LdGCLC). Moreover, oleuropein was able to mount a significant Th1 polarization characterized by the expression of immune genes (IL-12\u03b2, IL-10, TGF-\u03b21, IFN-\u03b3) and transcription factors (Tbx21 and GATA3). Moreover, this immunomodulatory effect was also correlated with an inhibitory effect on IL-1\u03b2 gene expression, rather than with the expression of IL-1\u03b1, IL-1rn and TNF-\u03b1. Furthermore, oleuropein-treated BALB/c mice mounted a delayed-type hypersensitivity (DTH) response and an elevated Leishmania-specific IgG2a/IgG1 ratio that clearly demonstrated an in vivo protective mechanism.",
            "output": [
                "Is the leishmanicidal activity of oleuropein selectively regulated through inflammation- and oxidative stress-related genes?"
            ]
        },
        {
            "id": "task847-17790b15b5bc4b68b76d45b653cb5a8a",
            "input": "Primary human hepatocytes offer the best human in vitro model for studies on human liver cell metabolism. Investigators use a variety of different media supplements and matrix biocoatings and the type of culture system used may influence the outcome.', 'To optimize in vitro conditions for primary human hepatocytes with regard to bile acid synthesis.', 'Human hepatocytes were isolated and cultured on collagen type I or EHS matrigel in cell media with or without dexamethasone. The glucocorticoid receptor (GR) antagonist RU486 was used to elucidate the involvement of GR.', 'Hepatocytes cultured on EHS matrigel produced more bile acids and expressed higher levels of cholesterol 7\u03b1-hydroxylase (CYP7A1) than cells cultured on rat tail collagen. Supplementation with dexamethasone increased the formation of cholic acid (CA) and decreased chenodeoxycholic acid formation. In line with these results, the mRNA expression of sterol 12\u03b1-hydroxylase (CYP8B1) increased following dexamethasone treatment. Surprisingly, the mRNA expression of CYP7A1 and CYP27A1 was not increased to the same extent. By using the GR antagonist RU486, we concluded that CYP8B1 induction is mediated via a GR-independent pathway. An altered expression of retinoid-related orphan receptor (ROR) \u03b1 and ROR \u03b1 target gene Glucose-6-phosphatase (G6Pase) suggests that ROR \u03b1 signaling may regulate CYP8B1 expression.",
            "output": [
                "Does addition of Dexamethasone alter the Bile Acid Composition by Inducing CYP8B1 in Primary Cultures of Human Hepatocytes?"
            ]
        },
        {
            "id": "task847-8b7b95fc414c4f6fbb4641dab9776abf",
            "input": "G. rigescens Franch (Long Dan Cao in Chinese) is a well-known TCM herb. It is clinically used with other drugs for the treatment of brain diseases such as epilepsy, postherpetic neuralgia in China.', 'In our previous study, the 11 dihydroxybenzoates compounds with NGF mimicking activity from G. rigescens Franch were found. In the present study, the neurogenesis and neuroprotection of a mixture of benzoates (\\xa0n-GS) were investigated in animal level.', 'The NGF mimicking activity of n-GS from G. rigescens Franch was examined in PC12 cells. The neurogenesis effects of n-GS were investigated in ICR mice with 5-bromo-2-deoxyuridine (BrdU) and neuronal neclei (NeuN) double immunostaining. Furthermore, the neuroprotection effects of n-GS on the memory in a scopolamine (SCO)-induced mouse model were evaluated with animal behavior tests.', \"The NGF-mimicking function and neurogenesis of n-GS were observed in PC12 cells and in normal mice. Subsequently, we investigated the effects of n-GS on the memory in a SCO-induced mouse model. In Y-maze test, SCO significantly lowered the alternation. This finding was reversed by n-GS and donepezil (DONE). SCO significantly impaired the mice's performance in novel object recognition (NOR) and Morris water maze (MWM) tests. The time spent to explore the novel object was longer in the n-GS- and DONE-treated groups than in the SCO control group. In the MWM test, the escape latency of n-GS- and DONE-treated groups was shorter than that of the SCO control group. Mechanism study showed that SCO significantly reduced superoxide dismutase (SOD) but increased the activities of acetylcholinesterase (AChE) and the levels of malondialdehyde (MDA) in the hippocampus and cerebral cortex, which all can be improved by n-GS and DONE. Additionally, the phosphorylation of type 1 insulin-like growth factor (IGF-1) receptor, extracellular signal-regulated kinase (ERK), and cAMP responsive element-binding (CREB) protein in the hippocampus was significantly up-regulated in the treatment group compared with that in the SCO group.",
            "output": [
                "Does benzoate fraction from Gentiana rigescens Franch alleviate scopolamine-induced impaired memory in mice model in vivo?"
            ]
        },
        {
            "id": "task847-62ad75a3fc24455284f273bc48590f68",
            "input": "Dynamin-related protein 1 (Drp1) is a newly discovered therapeutic target for tumor initiation, migration, proliferation, and chemosensitivity. In the present study, we aimed to examine the level of expression and distribution of DRP1 in glioma tissues and explore the concrete mechanism of DRP1 played in glioma.', 'Expression of DRP1 in glioma tissues was determined by immunohistochemistry staining. The DRP1 gene was knocked down using small interfering RNA, and was overexpressed using plasmids in glioma cells. To assess changes in cell function, in\\xa0vitro assays for invasion and growth were applied. Protein expression was tested by using Western-blot method. Variation of F-actin in cells was analyzed using immunofluorescence staining. Interactions between proteins were determined by co-immunoprecipitation.', 'The protein expression levels of DRP1 were significantly increased in glioma tissues compared to the normal brain tissues. Down-regulation of DRP1 decreased cell proliferation and invasion, and inhibited the formation of pseudopodias and microvillis. Moreover, a possible link between DRP1 and RHOA was confirmed when interactions between these two proteins were observed in the cells.",
            "output": [
                "Does silencing Drp1 inhibit glioma cells proliferation and invasion by RHOA/ ROCK1 pathway?"
            ]
        },
        {
            "id": "task847-e1f1aad3c1f5413aa99e6128d54b2776",
            "input": "Linear furrows are the most frequently found endoscopic abnormality in patients with esophageal eosinophilia (EE); however, the precise endoscopic features remain to be fully elucidated. Here, we aimed to clarify the endoscopic features of EE, essential for the diagnosis of eosinophilic esophagitis (EoE), by focusing on the specific locations of linear furrows in a Japanese population.', 'We enrolled 70 cases with EE (\u226515\\xa0eosinophils/high-power field) who were diagnosed at our hospital and related facilities. Information regarding endoscopic findings and clinical parameters was retrospectively reviewed. Next, the position of linear furrows in relation to esophageal longitudinal folds (ridge or valley) was evaluated in each case and compared with the position of mucosal breaks in patients with reflux esophagitis. Finally, the relationship between linear furrows and eosinophilic infiltration was evaluated.', 'Of the 70 EE patients, 63 (90%) had linear furrows. Those occurred in a radial pattern and were widespread throughout the lower to upper esophagus, and exclusively found in esophageal longitudinal mucosal fold valleys, not on ridges, which was different from the position of mucosal breaks in patients with reflux esophagitis. Increased eosinophilic infiltration was significantly more frequent in linear furrows in the valleys (93%) as compared to mucosa on adjacent ridges (60%) (P\\xa0<\\xa00.05).",
            "output": [
                "Does specific locations of linear furrow in patients with esophageal eosinophilia?"
            ]
        },
        {
            "id": "task847-45585cd7933b46aab2fd857cbb0b329f",
            "input": "In Crohn's disease (CD), rapid response to anti-tumor necrosis factor therapy improves short- and medium-term outcomes, but the relationship between early remission (ER) and long-term remission is unclear.\", 'This exploratory analysis of PRECiSE 3 (NCT00160524) assessed whether ER after initiation of certolizumab pegol predicted long-term remission.', 'Patients enrolled in PRECiSE 3 had completed PRECiSE 1 or 2, two randomized placebo-controlled studies for moderate to severe CD, and received open-label certolizumab pegol 400\\u2009mg every 4 weeks for a total treatment duration of \u22647.5 years. Time to loss of remission between patients with and without ER (Harvey-Bradshaw Index \u22644 at or before Week 6 of PRECiSE 1 or 2) was compared by log-rank test of Kaplan-Meier estimates.', 'At baseline, patients with (n\\u2009=\\u2009242) and without (n\\u2009=\\u2009148) ER had mean (standard deviation [SD]) durations of CD of 6.8 (6.6) and 7.4 (7.8) years, mean (SD) CD Activity Index scores of 280.3 (53.4) and 311.1 (55.5), with 45.5% and 41.9% of patients having ileocolonic CD, and median C-reactive protein concentrations of 8.0 and 5.0\\u2009mg/L, respectively. Median certolizumab pegol plasma concentrations during the first 6 weeks of therapy were similar in both groups. Mean time to loss of remission was significantly longer in patients with versus without ER (2.77 vs. 1.14 years, p\\u2009<\\u20090.0001).",
            "output": [
                "Does early remission status predict long-term outcomes in patients with Crohn 's disease treated with certolizumab pegol?"
            ]
        },
        {
            "id": "task847-889ec2dbed914dfe93b9eaa30f681f69",
            "input": "Psychomotor abnormalities characterize both unipolar (UP) depression and bipolar (BP) depression. We aimed to assess their neurobiological correlates in terms of motor activity (AL) and resting-state cerebral blood flow (rCBF) and investigate their association in BP, UP, and healthy controls (HC).', 'We enrolled 42 depressed patients (22 BP, 20 UP) and 19 HC matched for age, gender, education, income. AL and rCBF were objectively assessed with the use of wrist actigraphy and arterial spin labeling. Group differences and the association of AL and rCBF were computed.', 'Activity level was significantly reduced in patients, but no difference was found between BP and UP. Increased perfusion was found in BP compared with UP and HC, in multiple brain areas. We found positive correlations of rCBF and AL in BP and UP, in different parts of the insula and frontal regions. Only BP showed a cluster in the left precentral gyrus. In HC, only inverse correlations of AL and rCBF were found.",
            "output": [
                "Do distinct resting-state perfusion patterns underlie psychomotor retardation in unipolar vs. bipolar depression?"
            ]
        },
        {
            "id": "task847-be2cba4532934680a5b031dab7d8717c",
            "input": "Age-related cataract (ARC) is the leading cause of visual impairment worldwide, and \u03b1-crystallin (CRYAA) is the predominant structural protein involved in the maintenance of lens clarity and refractive properties. We previously demonstrated that CRYAA genes undergo epigenetic repression in the lens epithelia in ARC. We further analyze the underlying mechanism in the current study.', 'The transcription factor binding sites of the CpG island of CRYAA promoter were predicted by TESS website. An electrophoretic mobility shift assay (EMSA) was used to analyze the impact of the methylation of CpG sites on transcription factors. Human lens epithelial B-3 (HLE B-3) Cells were treated with demethylation agent zebularine in the concentrations of 0 (PBS as control), 10\\xa0\u03bcM, 20\\xa0\u03bcM, 50\\xa0\u03bcM, 100\\xa0\u03bcM and 200\\xa0\u03bcM, respectively. After treatment in the above concentrations for 24\\xa0h, 48\\xa0h and 72\\xa0h, respectively, CRYAA mRNA expression levels were detected by Quantitative Real-Time RT-PCR.', 'The methylation of the CpG site of the CRYAA promoter decreased the DNA-binding capacity of transcription factor Sp1. Zebularine increased CRYAA expression in HLE B-3 Cells in a dose- dependent and time- dependent pattern.",
            "output": [
                "Do cpG site methylation in CRYAA promoter affect transcription factor Sp1 binding in human lens epithelial cells?"
            ]
        },
        {
            "id": "task847-cf78d965b03c415c9eb1bab9c0e92ccd",
            "input": "Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer's disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model.\", 'We discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3.",
            "output": [
                "Does microRNA-34b mediate hippocampal astrocyte apoptosis in a rat model of recurrent seizures?"
            ]
        },
        {
            "id": "task847-1c4ebd5050ee49dfba402d990eedbc18",
            "input": "Cytochrome P450 oxidoreductase (POR) is the only flavoprotein that donates electrons to all microsomal P450 enzymes (CYP), and several POR SNPs have been shown to be important contributors to altered CYP activity or CYP-mediated drug metabolism. In this study we examined the association between 6 POR SNPs and tacrolimus concentrations in Chinese renal transplant recipients.', 'A total of 154 renal transplant recipients were enrolled. Genotyping of CYP3A5*3 and 6 POR SNPs was performed. All patients received a triple immunosuppressive regimen comprising tacrolimus, mycophenolate mofetil and prednisone. Dose-adjusted tacrolimus trough concentrations were obtained on d 7 (C0D7/D) after transplantation when steady-state concentration of tacrolimus was achieved (dosage had been unchanged for more than 3 d).', 'Tacrolimus C0D7/D in CYP3A5*3/*3/ POR rs1057868-rs2868177 GC-GT diplotype carriers was 1.62- and 2.72-fold higher than those in CYP3A5*3/*3/ POR rs1057868-rs2868177 GC-GT diplotype non-carriers and CYP3A5*1 carriers (220.17\u00b148.09 vs 135.69\u00b16.86 and 80.84\u00b15.27 ng/mL/mg/kg, respectively, P<0.0001). Of CYP3A5*3/*3/ POR rs1057868-rs2868177GC-GT diplotype carriers, 85.71% exceeded the upper limit of the target range (8 ng/mL), which was also significantly higher compared with the latter two groups (14.29% and 0.00%, respectively, P<0.0001). The CYP3A5*3 and POR rs1057868-rs2868177 GC-GT diplotype explained 31.7% and 5.7%, respectively, of the inter-individual variability of tacrolimus C0D7/D, whereas the POR rs1057868-rs2868177 GC-GT diplotype could explain 10.9% of the inter-individual variability of tacrolimus C0D7/D in CYP3A5 non-expressers.",
            "output": [
                "Is the POR rs1057868-rs2868177 GC-GT diplotype associated with high tacrolimus concentrations in early post-renal transplant recipients?"
            ]
        },
        {
            "id": "task847-211b329adfd3402c9e5b3a5413d3af38",
            "input": "Sweroside is an iridoid glycoside with diverse biological activities. In the present study we investigated the effects of sweroside on \u03b1-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in mice.', 'Mice received sweroside (120 mg\u00b7kg(-1)\u00b7d(-1), ig) or a positive control INT-747 (12 mg\u00b7kg(-1)\u00b7d(-1), ig) for 5 d, and ANIT (75 mg/kg, ig) was administered on d 3. The mice were euthanized on d 5, and serum biochemical markers, hepatic bile acids and histological changes were analyzed. Hepatic expression of genes related to pro-inflammatory mediators and bile acid metabolism was also assessed. Primary mouse hepatocytes were exposed to a reconstituted mixture of hepatic bile acids, which were markedly elevated in the ANIT-treated mice, and the cell viability and expression of genes related to pro-inflammatory mediators were examined.', 'Administration of sweroside or INT-747 effectively ameliorated ANIT-induced cholestatic liver injury in mice, as evidenced by significantly reduced serum biochemical markers and attenuated pathological changes in liver tissues. Furthermore, administration of sweroside or INT-747 significantly decreased ANIT-induced elevation of individual hepatic bile acids, such as \u03b2-MCA, CA, and TCA, which were related to its effects on the expression of genes responsible for bile acid synthesis and transport as well as pro-inflammatory responses. Treatment of mouse hepatocytes with the reconstituted bile acid mixture induced significant pro-inflammatory responses without affecting the cell viability.",
            "output": [
                "Does sweroside ameliorate \u03b1-naphthylisothiocyanate-induced cholestatic liver injury in mice by regulating bile acids and suppressing pro-inflammatory responses?"
            ]
        },
        {
            "id": "task847-2f77fb2fec4f4df8bf1558e5c35e8a74",
            "input": "Priming a high level construal has been shown to enhance self-control and reduce preference for indulgent food. Subtle visual cues have been shown to enhance the effects of a priming procedure. The current study therefore examined the combined impact of construal level and a visual cue reminder on the consumption of energy-dense snacks.', 'A student and community-based adult sample with a wide age and body mass index (BMI) range (N = 176) were randomly assigned to a high or low construal condition in which a novel symbol was embedded. Afterward participants completed a taste test of ad libitum snack foods in the presence or absence of the symbol.', 'The high (vs. the low) construal level prime successfully generated more abstract responses (p < .0001) and reduced intake when the cue-reminder was present (p = .02) but not when it was absent (p = .40).",
            "output": [
                "Is snack intake reduced using an implicit , high-level construal cue?"
            ]
        },
        {
            "id": "task847-2adce257f21447b7b9f1c6ceda707f88",
            "input": "Although trastuzumab improves the outcome of patients with human epidermal growth factor receptor\\xa02 (HER2)-overexpressing gastric or gastroesophageal junction adenocarcinoma (collectively referred to as \"gastroesophageal adenocarcinoma\"; GEA), no clinical response is observed in a substantial population of patients. A predictive biomarker of trastuzumab response is required. The aim of this study was to evaluate whether the hyperactivation of the downstream phosphatidylinositol 3-kinase pathway, due to phosphatase and tensin homolog (PTEN) loss or PIK3CA mutations, could provide trastuzumab resistance in GEA.', 'Expression of HER2 and PTEN, and PIK3CA gene mutations were screened in 264 surgically resected GEA specimens. The effects of PTEN knockdown on the response to trastuzumab on cell viability, HER2 downstream signaling, apoptosis, and cell cycle were evaluated in HER2-overexpressing NCI-N87 gastric adenocarcinoma and OE19 esophageal adenocarcinoma cell lines. Inhibition of xenograft tumor growth by trastuzumab was investigated in OE19 cells with or without PTEN knockdown. The PTEN expression and objective response were analyzed in 23 GEA patients who received trastuzumab-based therapy.', 'PTEN loss was identified in 34.5\\xa0% of HER2-overexpressing GEA patients, whereas PIK3CA mutations were rare (5.6\\xa0%). Trastuzumab-mediated growth suppression, apoptosis, and G",
            "output": [
                "Is pTEN loss associated with a poor response to trastuzumab in HER2-overexpressing gastroesophageal adenocarcinoma?"
            ]
        },
        {
            "id": "task847-fc714b590619451496c5ec20f47f7b3c",
            "input": "Fragility fractures are a major health care problem worldwide. Both hip and non-hip fractures are associated with excess mortality in the years following the fracture. Residents of long-term nursing homes represent a special high-risk group for poor outcomes. Orthogeriatric co-management models of care have shown in multiple studies to have medical as well as economic advantages, but their impact on this high-risk group has not been well studied.', 'We studied the outcome of long-term care residents with hip and non-hip fractures admitted to a geriatric fracture center.', 'The study design is a single center, prospective cohort study at a level-I trauma center in Austria running a geriatric fracture center. The cohort included all fragility fracture patients aged over 70 admitted from a long-term care residence from May 2009 to November 2011. The data set consisted of 265 patients; the mean age was 86.8\\xa0\u00b1\\xa06.7\\xa0years, and 80\\xa0% were female. The mean follow-up after the index fracture was 789\\xa0days, with a range from 1 to 1842\\xa0days. Basic clinical and demographic data were collected at hospital admission. Functional status and mobility were assessed during follow-up at 3, 6, and 12\\xa0months. Additional outcome data regarding readmissions for new fractures were obtained from the hospital information database; mortality was crosschecked with the death registry from the governmental institute of epidemiology.', '187 (70.6\\xa0%) patients died during the follow-up period, with 78 patients (29.4\\xa0%) dying in the first year. The mean life expectancy after the index fracture was 527 (\u00b1431) days. Differences in mortality rates between hip and non-hip fracture patients were not statistically significant. Compared to reported mortality rates in the literature, hip fracture patients in this orthogeriatric-comanaged cohort had a significantly reduced one-year mortality [OR of 0.57 (95\\xa0% CI 0.31-0.85)]. After adjustment for confounders, only older age (OR 1.091; p\\xa0=\\xa00.013; CI 1.019-1.169) and a lower Parker Mobility Scale (PMS) (OR 0.737; p\\xa0=\\xa00.022; CI 0.568-0.957) remained as independent predictors. During follow-up, 62 patients (23.4\\xa0%) sustained at least one subsequent fracture, and 10 patients (3.4\\xa0%) experienced multiple fractures; 29 patients (10.9\\xa0%) experienced an additional fracture within the first year. Nearly, half (47.1\\xa0%) regained their pre-fracture mobility based on the PMS.",
            "output": [
                "Does orthogeriatric co-management improve the outcome of long-term care residents with fragility fractures?"
            ]
        },
        {
            "id": "task847-1b110ccb9f0c4b8a8535d511427ab542",
            "input": "Total parenteral nutrition (TPN) is a cause of intestinal microbial dysbiosis and impaired gut barrier function. This may contribute to life-threatening parenteral nutrition-associated liver disease and sepsis in infants. We compared the effects of a lipid emulsion containing long-chain \u03c9-3 polyunsaturated fatty acids (PUFAs; SMOFlipid) and a predominantly \u03c9-6 PUFA emulsion (Intralipid) on microbial composition and host response at the mucosal surface.', 'Neonatal piglets were provided isocaloric, isonitrogenous TPN for 14 days versus sow-fed (SF) controls. Equivalent lipid doses (10 g/kg/d) were given of either SMOFlipid (ML; n = 10) or Intralipid (SO; n = 9). Ileal segments and mucosal scrapings were used to characterize microbial composition by 16S rRNA gene sequencing and quantitative gene expression of tight junction proteins, mucins, antimicrobial peptides, and inflammatory cytokines.', 'The microbial composition of TPN piglets differed from SF, while ML and SO differed from each other (analysis of molecular variance; P < .05); ML piglets were more similar to SF, as indicated by UniFrac distance (P < .05). SO piglets showed a specific and dramatic increase in Parabacteroides (P < .05), while ML showed an increase in Enterobacteriaceae (P < .05). Gene expression of mucin, claudin 1, \u03b2-defensin 2, and interleukin 8 were higher in TPN; overall increases were significantly less in ML versus SO (P < .05).",
            "output": [
                "Does lipid Emulsion Formulation of Parenteral Nutrition affect Intestinal Microbiota and Host Responses in Neonatal Piglets?"
            ]
        },
        {
            "id": "task847-2b677c41d3644cdd8654239c73cebc57",
            "input": "Coagulation and complement systems are simultaneously activated at sites of tissue injury, leading to thrombin generation and opsonisation with C3b. Thrombomodulin (TM) is a cell-bound regulator of thrombin activation, but can also enhance the regulatory activity of complement factor H (FH), thus accelerating the degradation of C3b into inactive iC3b.', 'This study sought to determine the biophysical interaction affinities of two recombinant TM analogs with thrombin, FH and C3b in order to analyze their ability to regulate serum complement activity.', 'Surface plasmon resonance (SPR) analysis was used to determine binding affinities of TM analogs with FH and C3b, and compared to thrombin as positive control. The capacity of the two recombinant TM analogs to regulate complement in serum was tested in standard complement hemolytic activity assays.', 'SPR analysis showed that both TM analogs bind FH and C3b-Factor H with nanomolar and C3b with micromolar affinity; binding affinity for its natural ligand thrombin was several fold higher than for FH. At a physiological relevant concentration, TM inhibits complement hemolytic activity in serum via FH dependent and independent mechanisms.",
            "output": [
                "Does thrombomodulin enhance complement regulation through strong affinity interactions with factor H and C3b-Factor H complex?"
            ]
        },
        {
            "id": "task847-58724c3d9d0443299e5a474a92750d2d",
            "input": "There are many patients that exhibit connective tissue related cardiac malformations but do not have mutations in collagen genes. The Small Leucine Rich Proteoglycans (SLRP) fibromodulin (FMOD) and lumican (LUM) bind collagen and regulate fibril assembly in other biological contexts.', 'FMOD deficient mice and double deficient FMOD; LUM mice exhibited anomalies in regions where cardiac valve tissue interdigitates with adjacent muscle for support. Ectopic connective and/or myocardial tissue(s) was associated with the more severe cardiac valve anomalies in FMOD; LUM deficient mice. At postnatal day 0 (P0) there was an increase in the mesenchymal cell number in the regions where valve cusps anchor in FMOD; LUM deficient mice compared to WT. The cardiac valve anomalies correlated with the highest levels of FMOD expression in the heart and also where myotendinous junctions (MTJ) components biglycan, collagen type I alpha 1, and collagen type VI, are also localized.",
            "output": [
                "Do development of myotendinous-like junctions that anchor cardiac valves requires fibromodulin and lumican?"
            ]
        },
        {
            "id": "task847-cf58dbe5515a400189baa1e5a5c8ef39",
            "input": "The glycolysis-derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part of the Danish arm of the ADDITION-Europe trial (ADDITION-DK).', 'Biobank serum samples collected at ADDITION-DK baseline (2001-2006) and follow-up (2009-2010) were used in the current analysis of methylglyoxal. We assessed cross-sectional baseline and longitudinal associations between methylglyoxal and urinary albumin-to-creatinine ratio (ACR) or estimated GFR (eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR.', 'Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow-up was inversely associated with change in eGFR (-1.6 ml/min/1.73 m",
            "output": [
                "Is methylglyoxal associated with changes in kidney function among individuals with screen-detected Type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-560966f4d4a84c59a146c575d5aaa16f",
            "input": "Osteolysis which leads to aseptic loosening of implants is a fundamental problem in joint replacement surgery (arthroplasty) and the leading cause for implant failure and revision surgery. Metal (CoCr) particles separated from implants by wear cause osteolysis and the failure of orthopedic implants, but the molecular mechanism is not clear. The chemokine receptor CXCR4 has been shown to play a pivotal role in periprosthetic osteolysis. The aim of this study was to determine which signal transduction pathway (PLC-DAG-PKC or MAPK/ERK) induces CXCR4 expression in osteoblast-like cells (MG63) cells.', 'MG63 and Jurkat cells were stimulated with different amounts of particles (10', 'Real-time PCR data showed that CXCR4 mRNA expression in MG63 cells induced by CoCr particles was significantly diminished by the PKC-specific inhibitor chelerythrine. This effect was not observed with the MAPK/ERK inhibitor PD98059. The involvement of PKC was also confirmed by an intensified phosphorylation pattern after stimulation with CoCr particles. In Jurkat cells, none of the inhibitors exhibited any effect.",
            "output": [
                "Is the induction of CXCR4 expression in human osteoblast-like cells ( MG63 ) by CoCr particles regulated by the PLC-DAG-PKC pathway?"
            ]
        },
        {
            "id": "task847-0f060558e4994425a583d352c5008582",
            "input": "To date, studies with ingenol mebutate gel have used clinical clearance, not histological clearance, as a primary efficacy endpoint.', 'This phase I, multicentre, single-arm, open-label study sought to confirm histologically the clinical clearance of actinic keratoses (AKs) to support a treatment effect deep in the epidermis.', 'Patients (n = 108) aged \u2265 18 years with histologically confirmed AK within a 25-cm', 'The observed agreement rate between clinical and histological assessments of clearance of a single AK was 81\u00b79% and the positive predictive value of a clinical assessment of clearance was 87%. Agreement between the two pathologists was 88%. The common composite 8-week complete clearance rate was 41% (95% confidence interval 32-50). Observed agreement rates between RCM and pathologist I and II assessments of clearance were 72\u00b79% and 81\u00b74%, respectively. Overall, 30 patients (27\u00b78%) experienced 38 adverse events (AEs). Application-site pain (four patients, 3\u00b77%) was the most common treatment-related AE inside the treatment area.",
            "output": [
                "Does histological examination confirm clinical clearance of actinic keratoses following treatment with ingenol mebutate 0\u00b705 % gel?"
            ]
        },
        {
            "id": "task847-2cea2ee8cd604423a0af96f14931be1e",
            "input": "Regulatory T cell (Treg) is required for the maintenance of tolerance to various tissue antigens and to protect the host from autoimmune disorders. However, Treg may, indirectly, support cancer progression and bacterial infections. Therefore, a balance of Treg function is pivotal for adequate immune responses. Acid sphingomyelinase (ASM) is a rate limiting enzyme involved in the production of ceramide by breaking down sphingomyelin. Previous studies in T-cells have suggested that ASM is involved in CD28 signalling, T lymphocyte granule secretion, degranulation, and vesicle shedding similar to the formation of phosphatidylserine-exposing microparticles from glial cells. However, whether ASM affects the development of Treg has not yet been described.', 'Splenocytes, isolated Naive T lymphocytes and cultured T cells were characterized for various immune T cell markers by flow cytometery. Cell proliferation was measured by Carboxyfluorescein succinimidyl ester (CFSE) dye, cell cycle analysis by Propidium Iodide (PI), mRNA transcripts by q-RT PCR and protein expression by Western Blotting respectively.', 'ASM deficient mice have higher number of Treg compared with littermate control mice. In vitro induction of ASM deficient T cells in the presence of TGF-\u03b2 and IL-2 lead to a significantly higher number of Foxp3+ induced Treg (iTreg) compared with control T-cells. Further, ASM deficient iTreg has less AKT (serine 473) phosphorylation and Rictor levels compared with control iTreg. Ceramide C6 led to significant reduction of iTreg in both ASM deficient and WT mice. The reduction in iTreg leads to induction of IL-1\u03b2, IL-6 and IL-17 but not IFN-\u03b3 mRNA levels.",
            "output": [
                "Is acid Sphingomyelinase ( ASM ) a Negative Regulator of Regulatory T Cell ( Treg ) Development?"
            ]
        },
        {
            "id": "task847-100cb6ed83244c8e960b7fe6a52fcd02",
            "input": "The objective of this study was to evaluate the effect of an intra-aortic filter on postoperative outcomes in high-risk cardiac surgical patients.', 'An intra-aortic filter was used in 316 (4.9%) of 6442 cardiac surgical cases from 2003 to 2013. A retrospective analysis of the Society of Thoracic Surgeons (STS) registry data was performed for 204 patients with filter placement who underwent coronary artery bypass grafting (CABG) (n = 89), valve replacement (n = 63) or combined CABG and valve replacement (n = 52), matched with 1224 patients without filter placement by STS mortality scores based on propensity scores. Generalized linear modelling was used to compare rates of complications as well as the length of stay and time in the intensive care unit (ICU). A P-value < 0.05 was considered significant.', 'Overall, patients with filters before matching had a significantly higher risk of death than did the patients without filters: 12.0% of patients with filters had an STS mortality risk score \u22654 vs 7.7% of patients without filters (P = 0.027). After analysis of the composite end-point of all STS major morbidities, the matched filter group had fewer overall complications (6.8 vs 13.2%, P = 0.02). The rate of postoperative respiratory failure was lower in the filter group (2.5 vs 7.0%, P = 0.01). Rates of stroke and new-onset haemodialysis, while not statistically different, were almost 50% lower in the filter group. Length of stay in the hospital and in the ICU was not significantly different; however, in patients with postoperative complications, time in the ICU (163 vs 189 h, P = 0.02) was shorter for the filter patients.",
            "output": [
                "Does selective use of the intra-aortic filter in high-risk cardiac surgical patients lead to better postoperative outcomes?"
            ]
        },
        {
            "id": "task847-f60112b2980844b2a89f23123d062ec4",
            "input": "While localized malignancies often respond to available therapies, most disseminated cancers are refractory. Novel approaches, therefore, are needed for the treatment of metastatic disease. CUB domain-containing protein1 (CDCP1) plays an important role in metastasis and drug resistance; the mechanism however, is poorly understood.', 'Breast cancer cell lines were engineered to stably express EGFR, CDCP1 or phosphorylation site mutants of CDCP1. These cell lines were used for immunoblot analysis or affinity purification followed by immunoblot analysis to assess protein phosphorylation and/or protein complex formation with CDCP1. Kinase activity was evaluated using phosphorylation site-specific antibodies and immunoblot analysis in in vitro kinase assays. Protein band excision and mass spectrometry was utilized to further identify proteins complexed with CDCP1 or \u0394CDCP1, which is a mimetic of the cleaved form of CDCP1. Cell detachment was assessed using cell counting.', 'This paper reports that CDCP1 forms ternary protein complexes with Src and EGFR, facilitating Src activation and Src-dependent EGFR transactivation. Importantly, we have discovered that a class of compounds termed Disulfide bond Disrupting Agents (DDAs) blocks CDCP1/EGFR/Src ternary complex formation and downstream signaling. CDCP1 and EGFR cooperate to induce detachment of breast cancer cells from the substratum and to disrupt adherens junctions. Analysis of CDCP1-containing complexes using proteomics techniques reveals that CDCP1 associates with several proteins involved in cell adhesion, including adherens junction and desmosomal cadherins, and cytoskeletal elements.",
            "output": [
                "Do cUB domain-containing protein 1 and the epidermal growth factor receptor cooperate to induce cell detachment?"
            ]
        },
        {
            "id": "task847-023d1a659feb4cfaab46784eb953cd45",
            "input": "The objective of this study was to study how changing the ratio of Lys to Thr, Lys to His, and Lys to Val affects the expression of lipogenic genes and microRNA (miRNA) in bovine mammary epithelial cells.', 'Triplicate cultures with the respective \"optimal\" amino acid (AA) ratio (OPAA\\u2009=\\u2009Lys:Met 2.9:1; Thr:Phe 1.05:1; Lys:Thr 1.8:1; Lys:His 2.38:1; Lys:Val 1.23:1) plus rapamycin (OPAARMC; positive control), OPAA, Lys:Thr 2.1:1 (LT2.1), Lys:Thr 1.3:1 (LT1.3), Lys:His 3.05:1 (LH3.0), or Lys:Val 1.62:1 (LV1.6) were incubated in lactogenic medium for 12\\xa0h. The expression of 15 lipogenic genes and 7 miRNA were evaluated. Responses to LT2.1, LT1.3, LH3.0, and LV1.6 relative to the control (OPAARMC) included up-regulated expression of ACSS2, FABP3, ACACA, FASN, SCD, LPIN1, INSIG1, SREBF1, PPARD, and NR1H3 (commonly known as LXR-\u03b1). Furthermore, LV1.6 up-regulated expression of ACSL1, DGAT1, and RXRA and down-regulated PPARG expression. Although no effect of OPAA on expression of PPARG was observed, compared with the control, OPAA up-regulated expression of the PPAR targets ACSS2, FABP3, ACACA, FASN, SCD, LPIN1, INSIG1, and SREBF1. Compared with the control, the expression of the anti-lipogenic MIR27AB was down-regulated by OPAA, LT2.1, LT1.3 and LH3.0. In contrast, compared with the control, the expression of the pro-lipogenic MIR21 was up-regulated by LT2.1, LT1.3, LH3.0, and LV1.6.",
            "output": [
                "Do essential amino acid ratios and mTOR affect lipogenic gene networks and miRNA expression in bovine mammary epithelial cells?"
            ]
        },
        {
            "id": "task847-dd257389ac984af7a2564d3d18083c20",
            "input": "It is well established that environmental toxins, such as exposure to arsenic, are risk factors in the development of urinary bladder cancer, yet recent genome-wide association studies (GWAS) provide compelling evidence that there is a strong genetic component associated with disease predisposition. A single-nucleotide polymorphism (SNP), rs8102137, was identified on chromosome 19q12, residing 6 kb upstream of the important cell-cycle regulator and proto-oncogene, Cyclin E1 (CCNE1). However, the functional role of this variant in bladder cancer predisposition has been unclear because it lies within a non-coding region of the genome. Here, it is demonstrated that bladder cancer cells heterozygous for this SNP exhibit biased allelic expression of CCNE1 with 1.5-fold more transcription occurring from the risk allele. Furthermore, using chromatin immunoprecipitation assays, a novel enhancer element was identified within the first intron of CCNE1 that binds Kruppel-like Factor 5 (KLF5), a known transcriptional activator in bladder cancer. Moreover, the data reveal that the presence of rs200996365, a SNP in high-linkage disequilibrium with rs8102137 residing in the center of a KLF5 motif, alters KLF5 binding to this genomic region. Through luciferase assays and CRISPR-Cas9 genome editing, a novel polymorphic intronic regulatory element controlling CCNE1 transcription is characterized. These studies uncover how a cancer-associated polymorphism mechanistically contributes to an increased predisposition for bladder cancer development.",
            "output": [
                "Does transcription Factor KLF5 bound a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk?"
            ]
        },
        {
            "id": "task847-df29036e784e43c9a5f67e7e094457aa",
            "input": "Adipose tissue derived-mesenchymal stem cells (AMSCs) are one of the most widely used MSCs in the cell therapy for regenerative medicine. In the current study, the role of CXCL13 in AMSCs and its potential signaling pathway were investigated.', 'AMSCs were isolated from adipose tissue of healthy subjects. After administrating the cells with CXCL13, the expression levels of miR-23a and runt-related transcription factor 2 (Runx2) were assessed by real-time PCR and western blot. The alterations of phosphoinositide-3 kinase (PI3K)/Akt, stress-activated protein kinase (SAPK)/c-jun kinase (JNK), and extracellular-signal-regulated kinase (ERK1/2) pathways were also evaluated.', 'CXCL13 down-regulated miR-23a and up-regulated Runx2 expression in AMSCs. The inhibitor specific for PI3K/AKT, but not SAPK/JNK and ERK ERK1/2, reversed the effects of CXCL13 on miR-23a and Runx2 expression.",
            "output": [
                "Does cXCL13 inhibit microRNA-23a through PI3K/AKT signaling pathway in adipose tissue derived-mesenchymal stem cells?"
            ]
        },
        {
            "id": "task847-ecb3c06fdbdb4e83992c1cd8a5bb70fd",
            "input": ": Finding appropriate seed cells for bone tissue engineering remains a significant challenge. Considering that skin is the largest organ, we hypothesized that human bone morphogenetic protein receptor type IB (BmprIB)+ dermal cells could have enhanced osteogenic capacity in the healing of critical-sized calvarial defects in an immunodeficient mouse model. In this study, immunohistochemical staining revealed that BmprIB was expressed throughout reticular dermal cells; the positive expression rate of BmprIB was 3.5% \u00b1 0.4% in freshly separated dermal cells, by flow cytometry. Furthermore, in vitro osteogenic capacity of BmprIB+ cells was confirmed by osteogenic-related staining and marker gene expression compared with unsorted dermal cells. In vivo osteogenic capacity was demonstrated by implantation of human BmprIB+ cell/coral constructs in the treatment of 4-mm diameter calvarial defects in an immunodeficient mouse model compared with implantation of unsorted cell/coral constructs and coral scaffold alone. These results indicate that the selective cell population BmprIB from human dermis is a promising osteogenic progenitor cell that can be a large-quantity and high-quality cell source for bone tissue engineering and regeneration.",
            "output": [
                "Does a Selective Cell Population From Dermis strengthen Bone Regeneration?"
            ]
        },
        {
            "id": "task847-d1e19de002a24821ad49830abc52ab59",
            "input": "There has been growing interest in the role that implicit processing of drug cues can play in motivating drug use behavior. However, the extent to which drug cue processing biases relate to the processing biases exhibited to other types of evocative stimuli is largely unknown. The goal of the present study was to determine how the implicit cognitive processing of smoking cues relates to the processing of affective cues using a novel paradigm.', 'Smokers (n = 50) and nonsmokers (n = 38) completed a picture-viewing task, in which participants were presented with a series of smoking, pleasant, unpleasant, and neutral images while engaging in a distractor task designed to direct controlled resources away from conscious processing of image content. Electroencephalogram recordings were obtained throughout the task for extraction of event-related potentials (ERPs).', 'Smokers exhibited differential processing of smoking cues across 3 different ERP indices compared with nonsmokers. Comparable effects were found for pleasant cues on 2 of these indices. Late cognitive processing of smoking and pleasant cues was associated with nicotine dependence and cigarette use.",
            "output": [
                "Do smokers exhibit biased neural processing of smoking and affective images?"
            ]
        },
        {
            "id": "task847-04736136d4104c6a8b49d4623a189daf",
            "input": "Physical activity is beneficial for cancer survivors, but exercise participation is low in this population. It is therefore important to understand the psychological factors underlying exercise uptake so that more effective interventions can be developed. Social-cognitive theory constructs such as outcome expectancies predict exercise behavior, but self-report measures have several limitations. We examined the associations between implicit (automatic) cognitions and exercise behavior and self-efficacy in endometrial cancer survivors.', 'This was a longitudinal study to examine predictors of exercise behavior in female endometrial cancer survivors who all received an exercise intervention. Participants (N = 100, mean age of 57.0) completed questionnaires to assess self-report exercise-related measures (outcome expectancy and attitudes about and identification with exercise) and reaction time (RT) tasks to assess implicit exercise cognitions (expectancy accessibility, implicit attitudes about exercise, and implicit self-identification with exercise) at baseline and at 2, 4, and 6 months at follow-up. Exercise behavior was measured using accelerometers and self-report. Data were analyzed using linear mixed models.', 'Expectancy accessibility was associated with exercise duration independent of the corresponding self-report measure. Exercise implicit attitudes and self-identification were prospectively associated with exercise self-efficacy only after adjustment for the corresponding self-report measures and baseline self-efficacy. Self-report measures were also associated with study outcomes.",
            "output": [
                "Are self-reported and automatic cognitions associated with exercise behavior in cancer survivors?"
            ]
        },
        {
            "id": "task847-42b5ba1dca7f4ec1ac0a3c760061752c",
            "input": "Lasiodiplodia theobromae is a fungus of the Botryosphaeriaceae that causes grapevine vascular disease, especially in regions with hot climates. Fungi in this group often remain latent within their host and become virulent under abiotic stress. Transcriptional regulation analysis of L. theobromae exposed to heat stress (HS) was first carried out in vitro in the presence of grapevine wood (GW) to identify potential pathogenicity genes that were later evaluated for in planta expression.', 'A total of 19,860 de novo assembled transcripts were obtained, forty-nine per cent of which showed homology to the Botryosphaeriaceae fungi, Neofusicoccum parvum or Macrophomina phaseolina. Three hundred ninety-nine have homology with genes involved in pathogenic processes and several belonged to expanded gene families in others fungal grapevine vascular pathogens. Gene expression analysis showed changes in fungal metabolism of phenolic compounds; where genes encoding for enzymes, with the ability to degrade salicylic acid (SA) and plant phenylpropanoid precursors, were up-regulated during in vitro HS response, in the presence of GW. These results suggest that the fungal L-tyrosine catabolism pathway could help the fungus to remove phenylpropanoid precursors thereby evading the host defense response. The in planta up-regulation of salicylate hydroxylase, intradiol ring cleavage dioxygenase and fumarylacetoacetase encoding genes, further supported this hypothesis. Those genes were even more up-regulated in HS-stressed plants, suggesting that fungus takes advantage of the increased phenylpropanoid precursors produced under stress. Pectate lyase was up-regulated while a putative amylase was down-regulated in planta, this could be associated with an intercellular growth strategy during the first stages of colonization.",
            "output": [
                "Does global transcriptional analysis suggest Lasiodiplodia theobromae pathogenicity factors involved in modulation of grapevine defensive response?"
            ]
        },
        {
            "id": "task847-5305f0b1b58c4386b3dbc7ac5805d9d0",
            "input": "To compare prognosis of clival chordomas with different dural penetration, and establish the relationship between dural penetration and platelet-derived growth factor receptor (PDGFR)-\u03b2 signaling pathway.', 'Tumors in Type I (33 cases) showed limited dural penetration, while those in Type II (34 cases) had more serious dural penetration. Cox multivariate regression analysis was used to analyze risk factors affecting survival. Kaplan-Meier analysis measured overall survival (OS) and progression-free survival (PFS). To determine relationship between dural penetration and PDGFR-\u03b2 signaling, expression of PDGFR-\u03b2, Akt, mammalian target of rapamycin (mTOR), and phosphatase and tensin homolog (PTEN) expression was compared using immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and western blotting.', 'Total resection was achieved in nine cases in Type I and eleven in Type II. There were significant correlations between OS and dural penetration (P=0.032) and age (P=0.034). PFS correlated significantly with dural penetration (P=0.022), gender (P=0.001), and degree of resection (P=0.001). Mean OS in Type I was significantly longer than in Type II (P=0.046). Patients aged <55 years had longer OS than those aged \u226555 years (P=0.004). Total resection was correlated with longer PFS (P=0.011). Among patients with tumor totally resected, mean PFS in Type I was significantly longer than in Type II (P=0.007). Expression of PDGFR-\u03b2 in Type II was higher than in Type I.",
            "output": [
                "Are differences in dural penetration of clival chordomas associated with different prognosis and expression of platelet-derived growth factor receptor-\u03b2?"
            ]
        },
        {
            "id": "task847-4e49778ab7434466a334594ab32e50d1",
            "input": "Developmental coordination disorder is a common neurodevelopment disorder that frequently co-occurs with other neurodevelopmental disorders including attention-deficit hyperactivity disorder (ADHD). Copy-number variations (CNVs) have been implicated in a number of neurodevelopmental and psychiatric disorders; however, the proportion of heritability in developmental coordination disorder (DCD) attributed to CNVs has not been explored.', 'This study aims to investigate how CNVs may contribute to the genetic architecture of DCD.', 'CNV analysis was performed on 82 extensively phenotyped Canadian children with DCD, with or without co-occurring ADHD and/or reading disorder, and 2988 healthy European controls using identical genome-wide SNP microarrays and CNV calling algorithms.', 'An increased rate of large and rare genic CNVs (p=0.009) was detected, and there was an enrichment of duplications spanning brain-expressed genes (p=0.039) and genes previously implicated in other neurodevelopmental disorders (p=0.043). Genes and loci of particular interest in this group included: GAP43, RBFOX1, PTPRN2, SHANK3, 16p11.2 and distal 22q11.2. Although no recurrent CNVs were identified, 26% of DCD cases, where sample availability permitted segregation analysis, were found to have a de novo rare CNV. Of the inherited CNVs, 64% were from a parent who also had a neurodevelopmental disorder.",
            "output": [
                "Are copy-number variations enriched for neurodevelopmental genes in children with developmental coordination disorder?"
            ]
        },
        {
            "id": "task847-8f2a019822794d9582074d356588cdb5",
            "input": "High-frequency oscillations (HFOs, 80-500Hz) are newly-described EEG markers of epileptogenicity. The proportion of physiological and pathological HFOs is unclear, as frequency analysis is insufficient for separating the two types of events. For instance, ripples (80-250Hz) also occur physiologically during memory consolidation processes in medial temporal lobe structures. We investigated the correlation between HFO rates and memory performance.', 'Patients investigated with bilateral medial temporal electrodes and an intellectual capacity allowing for memory testing were included. High-frequency oscillations were visually marked, and rates of HFOs were calculated for each channel during slow-wave sleep. Patients underwent three verbal and three nonverbal memory tests. They were grouped into severe impairment, some impairment, mostly intact, or intact for verbal and nonverbal memory. We calculated a Pearson correlation between HFO rates in the hippocampi and the memory category and compared HFO rates in each hippocampus with the corresponding (verbal - left, nonverbal - right) memory result using Wilcoxon rank-sum test.', 'Twenty patients were included; ten had bilateral, five had unilateral, and five had no memory impairment. Unilateral memory impairment was verbal in one patient and nonverbal in four. There was no correlation between HFO rates and memory performance in seizure onset areas. There was, however, a significant negative correlation between the overall memory performance and ripple rates (r=-0.50, p=0.03) outside the seizure onset zone.",
            "output": [
                "Do spontaneous ripples in the hippocampus correlate with epileptogenicity and not memory function in patients with refractory epilepsy?"
            ]
        },
        {
            "id": "task847-6c768be212c449769325d9f9eb311b30",
            "input": "Extensive research has explored the role of aldosterone in insulin resistance. Recent evidence suggests that the mineralocorticoid receptor (MR) mediates aldosterone-induced dysregulation of cytokines, and most of this research has focused on adjustments in fat tissue and adipocytes. However, the direct effect of MR blockade on insulin resistance in cardiomyocytes remains largely unknown. In the present study, we investigated whether MR blockade improves insulin-sensitizing factors in insulin-resistant rats and attenuates the dysregulation of the aldosterone-related transport of adiponectin and glucose in cardiomyocytes and examined the underlying mechanisms.', 'The effects of aldosterone, MR inhibitors (e.g., eplerenone), a peroxisome proliferator-activated receptor (PPAR) \u03b1 agonist, and a p38 mitogen-activated protein kinase (MAPK) inhibitor on adiponectin and glucose transport were studied at the mRNA and protein levels in vitro and in vivo.', 'Our data revealed that aldosterone reduced the expression of adiponectin and inhibited the transport of glucose in cardiomyocytes and that MR blockade reversed these affects. In vivo, MR blockade improved insulin-sensitive parameters and increased adiponectin expression in the myocardia of high-fat diet rats. Furthermore, aldosterone promoted p38MAPK expression but negatively affected PPAR\u03b1 expression, and the downregulation of adiponectin by aldosterone was reversed by MR blockade, a PPAR\u03b1 agonist, and a p38 MAPK inhibitor.",
            "output": [
                "Does mineralocorticoid Receptor Blockade improve Insulin Sensitivity in the Rat Heart and a Possible Molecular Mechanism?"
            ]
        },
        {
            "id": "task847-846f4998d97b47e392b501bd196fc41b",
            "input": "Previous studies have shown that birth order is an important predictor of later life health as well as socioeconomic attainment. In this study, we examine the relationship between birth order and hospitalization for alcohol and narcotics use in Sweden.', 'We study the relationship between birth order and hospitalization related to alcohol and narcotics use before and after the age of 20 using Swedish register data for cohorts born 1987-1994. We apply Cox proportional hazard models and use sibling fixed effects, eliminating confounding by factors shared by the siblings.', 'Before age 20 we find that later born siblings are hospitalized for alcohol use at a higher rate than first-borns, and there is a monotonic increase in the hazard of hospitalization with increasing birth order. Second-borns are hospitalized at a rate 47% higher than first-borns, and third-borns at a rate 65% higher. Similar patterns are observed for hospitalization for narcotics use. After age 20 the pattern is similar, but the association is weaker. These patterns are consistent across various sibling group sizes.",
            "output": [
                "Do birth order and hospitalization for alcohol and narcotics use in Sweden?"
            ]
        },
        {
            "id": "task847-25ac4c8261a740c4b82ec84a6d29c127",
            "input": "Nonspecific symptoms are common in all areas of medicine. Patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. We therefore asked the following questions: 1) Which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific arm pain to eventual identification of discrete pathophysiology that corresponds with symptoms? 2) What is the percentage of patients eventually diagnosed with discrete pathophysiology, what are those pathologies, and do they account for the symptoms?', 'We evaluated 634 patients with an isolated diagnosis of nonspecific upper extremity pain to see if discrete pathophysiology was diagnosed on subsequent visits to the same hand surgeon, a different hand surgeon, or any physician within our health system for the same pain.', 'There were too few patients with discrete pathophysiology at follow-up to address the primary study question. Definite discrete pathophysiology that corresponded with the symptoms was identified in subsequent evaluations by the index surgeon in one patient (0.16% of all patients) and cured with surgery (nodular fasciitis). Subsequent doctors identified possible discrete pathophysiology in one patient and speculative pathophysiology in four patients and the index surgeon identified possible discrete pathophysiology in four patients, but the five discrete diagnoses accounted for only a fraction of the symptoms.",
            "output": [
                "Is discrete Pathophysiology Uncommon in Patients with Nonspecific Arm Pain?"
            ]
        },
        {
            "id": "task847-a28ed198e9214f40bb999baaa6a37180",
            "input": "The Affordable Care Act (ACA) Medicaid expansion varies in availability across states.', 'We compared characteristics of low-income uninsured residents in both Medicaid nonexpanding and expanding states with respect to their dietary quality, health risk factors, and access to care.', 'Data from the 2007-2012 National Health and Nutrition Examination Survey was matched with the Kaiser Family Foundation Medicaid expansion data. Bivariate and multivariate regressions were estimated to assess differences across expanding and non-expanding states.', 'The non-expansion group had a lower Healthy Eating Index score (41.8 vs. 44.1, p-value=0.006), a higher Body Mass Index (29.9 vs. 28.9, p-value=0.032), higher obesity prevalence (41% vs. 33%, p-value=0.007), and lower asthma prevalence (14.8% vs. 19.7%, p-value=0.037) compared with the expansion group.",
            "output": [
                "States diet quality , risk factors and access to care among low-income uninsured American adults in states expanding Medicaid vs. expanding under the affordable care act?"
            ]
        },
        {
            "id": "task847-58fceaeb6ce44f8d97f4b065e38190a1",
            "input": "Combination therapy for cancer is more effective than using only standard chemo- or radiotherapy. Our previous results showed that dendritic cell-activated \u03b1-fetoprotein (AFP)-specific T-cells inhibit tumor in vitro and in vivo. In this study, we focused on antitumor function of CD8(+) T-cells combined with or without JAK2 inhibitor.', 'Proliferation and cell cycle were analyzed by CCK-8 and flow cytometry. Western blot was used to analyze the expression level of related protein and signaling pathway.', 'We demonstrated reduced viability and induction of apoptosis of tumor cells with combination treatment. Intriguingly, cell cycle was blocked at the G1 phase by using AFP-specific CD8(+) T-cells combined with JAK2 inhibitor (AG490). Furthermore, an enhanced expression of BAX but no influence on Fas/FasL was detected from the tumor cells.",
            "output": [
                "Does jAK2 inhibitor combined with DC-activated AFP-specific T-cells enhance antitumor function in a Fas/FasL signal-independent pathway?"
            ]
        },
        {
            "id": "task847-f3ed5995cc7845fe80cc9d06d803cf49",
            "input": "Paraneoplastic syndromes are serious immune caused diseases of the peripheral and/or central nervous system associated with malignant neoplasm. Symptoms develop when antibodies against antigens expressed by tumor cells cross-react with neuronal proteins. Antineuronal antibodies are usually examined in patient's sera while examination of the cerebrospinal fluid (CSF) often fails. Furthermore, the few previous reports describing CSF data summarized different antineuronal antibodies and/or regarded patients with different neurological symptoms as one group.\", 'We retrospectively evaluated data of 18 patients with paraneoplastic syndromes due to anti-Hu antibodies. The study aimed to differentiate patients with peripheral neuropathy and encephalitis by cerebrospinal fluid (CSF) parameters including anti-Hu antibody titers.', 'Our results confirm previous observations that serum titers of anti-Hu antibodies and standard CSF values do not differ between patients with neuropathy and encephalitis. However, analysis of CSF anti-Hu titers and calculating the intrathecal synthesis helped to discriminate between both groups.",
            "output": [
                "Does intrathecal synthesis of anti-Hu antibodies distinguish patients with paraneoplastic peripheral neuropathy and encephalitis?"
            ]
        },
        {
            "id": "task847-308c8aee3b61456c884a56ee052267a3",
            "input": "Non-response to cardiac resynchronization therapy (CRT) might be due to insufficient resynchronization as a result of a sub-optimal left ventricular lead positon (LV-LP).', 'To evaluate the impact of different LV-LPs on mortality and symptomatic improvement in a large cohort of patients treated with CRT.', \"We performed a nationwide cohort study on consecutive patients receiving a CRT device from 1997 to 2012 registered in the Danish pacemaker and ICD register. The LV-LP was defined clockwise in a left anterior oblique (LAO) view and categorized as anterior (\u22642 o'clock), lateral (2 to 4 o'clock) or posterior (>4 o'clock), and as basal, mid-ventricular, or apical in a right anterior oblique (RAO) view. Outcomes were all cause mortality and clinical response (improvement in NYHA class). Adjusted hazard ratio (aHR) and odds ratio (aOR) with 95% confidence intervals (CI) were calculated using Cox and logistic regression analysis.\", 'A total of 2594 patients were included. A lateral LV-LP, (aHR 0.77, 95% CI 0.64-0.92, p=0.004), and a posterior LV-LP, (aHR 0.71 95% CI 0.53-0.97, p=0.029) were associated with lower mortality as compared to an anterior LV-LP. A lateral LV-PV was associated with higher clinical response rate as compared to an anterior LV-LP (aOR 1.37, 1.03-1.83, p=0.032). No statistically significant associations were observed between LV-LP in the RAO view and mortality or clinical response.",
            "output": [
                "Is an anterior left ventricular lead position associated with increased mortality and non-response in cardiac resynchronization therapy?"
            ]
        },
        {
            "id": "task847-7f672d79d6e94d3e9ba7bc7615cd1c49",
            "input": "Cognitive tests and nonamyloid imaging biomarkers do not consistently identify preclinical AD. The objective of this study was to evaluate whether white matter hyperintensity (WMH) volume, a cerebrovascular disease marker, is more associated with preclinical AD than conventional AD biomarkers and cognitive tests.', \"Elderly controls enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI, n\\xa0=\\xa0158) underwent florbetapir-PET scans, psychometric testing, neuroimaging with MRI and PET, and APOE genetic testing. Elderly controls the Parkinson's progression markers initiative (PPMI, n\\xa0=\\xa058) had WMH volume, cerebrospinal fluid (CSF) A\u03b21-42, and APOE status measured.\", 'In the ADNI cohort, only WMH volume and APOE \u03b54 status were associated with cerebral A\u03b2 (standardized \u03b2\\xa0=\\xa00.44 and 1.25, P\\xa0=\\xa0.03 and .002). The association between WMH volume and APOE \u03b54 status with cerebral A\u03b2 (standardized \u03b2\\xa0=\\xa01.12 and 0.26, P\\xa0=\\xa0.048 and .045) was confirmed in the PPMI cohort.",
            "output": [
                "Are white matter hyperintensities more highly associated with preclinical Alzheimer 's disease than imaging and cognitive markers of neurodegeneration?"
            ]
        },
        {
            "id": "task847-f3d31173babf4193bc3579bc0b070a7a",
            "input": "The aim of this study was to investigate the association of lipoprotein(a) [Lp(a)] with the severity of coronary heart disease (CHD) in Han Chinese people.', 'Six hundred and seventy-nine patients with angiographically defined CHD were enrolled in this cross-sectional study. Fasting lipids were measured, and the severity of CHD was quantitatively assessed for each patient according to the number of stenotic coronary branches and the Gensini scoring system.', 'The levels of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and apolipoprotein (apo) B100 increased, while high-density lipoprotein cholesterol (HDL-C) and apoAI decreased significantly with the number of stenotic vessels. The levels of Lp(a) increased and HDL-C and apoAI decreased significantly with the Gensini scores. The logistic regression analyses showed that Lp(a) and HDL-C were independently associated with the number of stenotic coronary vessels after adjusting for age, weight, body mass index, sex, smoking, alcohol consumption, hypertension, diabetes, triglycerides, TC, LDL-C, VLDL-C, apoAI, and apoB100. However, only Lp(a) was independently associated with the Gensini scores after adjustment.",
            "output": [
                "Are plasma lipoprotein ( a ) levels associated with the severity of coronaryheart disease in Han Chinese people?"
            ]
        },
        {
            "id": "task847-237699d945b348899f9468233a4f209a",
            "input": "Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). We aimed to evaluate the efficacy of intramuscular diclofenac sodium for prophylaxis of post-ERCP pancreatitis (PEP) in comparison to the rectal form.', 'One hundred and fifty consecutive patients who underwent ERCP were enrolled in this single-center, prospective, randomized controlled study. Patients were randomized into three groups. The first group received 75 mg of diclofenac sodium via intramuscular route and the second group received 100 mg of diclofenac sodium rectally 30-90 min before the procedure. The third group served as the control group. Patients were evaluated for post-ERCP pancreatitis with serum amylase levels and abdominal pain 24 h after the procedure.', 'The overall incidence of PEP was 6% (n = 9) and 2% (n = 1) in the intramuscular (IM) and rectal groups, respectively, and 14% in the control group (P = 0.014). Nineteen (12.7%) patients developed post-ERCP abdominal pain (8% in IM, 10% in rectal, and 20% in control group; P = 0.154). Twenty-five (16.6%) patients developed post-ERCP hyperamylasemia (10% in IM, 12% in rectal, and 24% in control group; P = 0.03).",
            "output": [
                "Does rectal or intramuscular diclofenac reduce the incidence of pancreatitis afterendoscopic retrograde cholangiopancreatography?"
            ]
        },
        {
            "id": "task847-05c92b9fd02240a18014c2af39aad8d9",
            "input": "This study was aimed at understanding the effect of \u03b2-catenin and cyclin D1 on overall survival in patients with early-stage NSCLC and at evaluating if the\\xa0prognostic effect can be modified by adjuvant chemotherapy.', 'We retrospectively analyzed the expression of \u03b2-catenin and cyclin D1 using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 576 patients with early-stage NSCLC.', 'The median duration of follow-up was 5.1 years. Overexpression of \u03b2-catenin and cyclin D1 was found in 56% and 50% of 576 cases, respectively. Overexpression of \u03b2-catenin and cyclin D1 was significantly associated with poor overall survival (p\\xa0= 0.003 and p\\xa0= 0.0009, respectively; log rank test) in squamous cell carcinomas, not in adenocarcinomas. The prognostic significance of each protein in the squamous cell carcinomas was limited to stages IA, IB, and IIA. In addition, simultaneous overexpression of \u03b2-catenin and cyclin D1 in the squamous cell carcinomas synergistically increased hazard ratios (HRs) 15.79 (95% confidence interval [CI]\\xa0= 1.09-51.23; p\\xa0=0.04) for stage IA, 10.30 (95% CI\\xa0= 2.29-46.41; p\\xa0= 0.002) for stage 1B, and 3.55 (95% CI\\xa0= 1.22-10.36; p\\xa0= 0.02) times for stage 2A compared to those without overexpression of the two proteins, after adjusting for confounding factors. In addition, the effect was not dependent on adjuvant chemotherapy.",
            "output": [
                "Is overexpression of \u03b2-Catenin and Cyclin D1 Associated with Poor Overall Survival in Patients with Stage IA-IIA Squamous Cell Lung Cancer Irrespective of Adjuvant Chemotherapy?"
            ]
        },
        {
            "id": "task847-81e494d0e70c4c50add823f71a9ef302",
            "input": "The Synapsins (SYN1, SYN2, and SYN3) are important players in the adult brain, given their involvement in synaptic transmission and plasticity, as well as in the developing brain through roles in axon outgrowth and synaptogenesis. We and others previously reported gene expression dysregulation, both as increases and decreases, of Synapsins in mood disorders, but little is known about the regulatory mechanisms leading to these differences. Thus, we proposed to study DNA methylation at theses genes' promoter regions, under the assumption that altered epigenetic marks at key regulatory sites would be the cause of gene expression changes and thus part of the mood disorder etiology.\", \"We performed CpG methylation mapping focusing on the three genes' predicted CpG islands using the Sequenom EpiTYPER platform. DNA extracted from post-mortem brain tissue (BA10) from individuals who had lived with bipolar disorder (BD), major depressive disorder (MDD), as well as psychiatrically healthy individuals was used. Differences in methylation across all CpGs within a CpG island and between the three diagnostic groups were assessed by 2-way mixed model analyses of variance.\", 'We found no significant results for SYN1 or SYN3, but there was a significant group difference in SYN2 methylation, as well as an overall pattern of hypomethylation across the CpG island. Furthermore, we found a significant inverse correlation of DNA methylation with SYN2a mRNA expression.",
            "output": [
                "Does dNA hypomethylation of Synapsin II CpG islands associate with increased gene expression in bipolar disorder and major depression?"
            ]
        },
        {
            "id": "task847-9971e0325b344fcf80155e36d574f100",
            "input": "Slumped posture is a diagnostic feature of depression. While research shows upright posture improves self-esteem and mood in healthy samples, little research has investigated this in depressed samples. This study aimed to investigate whether changing posture could reduce negative affect and fatigue in people with mild to moderate depression undergoing a stressful task.', 'Sixty-one community participants who screened positive for mild to moderate depression were recruited into a study purportedly on the effects of physiotherapy tape on cognitive function. They were randomized to sit with usual posture or upright posture and physiotherapy tape was applied. Participants completed the Trier Social Stress Test speech task. Changes in affect and fatigue were assessed. The words spoken by the participants during their speeches were analysed.', 'At baseline, all participants had significantly more slumped posture than normative data. The postural manipulation significantly improved posture and increased high arousal positive affect and fatigue compared to usual posture. The upright group spoke significantly more words than the usual posture group, used fewer first person singular personal pronouns, but more sadness words. Upright shoulder angle was associated with lower negative affect and lower anxiety across both groups.",
            "output": [
                "Does upright posture improve affect and fatigue in people with depressive symptoms?"
            ]
        },
        {
            "id": "task847-238c1f85ee5c4a76b0c508e62e082431",
            "input": "Simvastatin has lung vascular-protective effects via augmentation of endothelial barrier function. Accordingly, on the basis of our previous study, we hypothesized that endothelial cell (EC) protection by simvastatin is dependent on the stabilization on cytoskeletons.', 'Sixty C57BL/6 mice were divided into two experimental groups: LPS group (L group) and LPS+simvastatin treated group (L+S group). All mice in these two groups received an intraperitoneal injection of LPS (10\\u200amg/kg/d). Simvastatin was administered intraperitoneally immediately after the LPS injection in animals of the L+S group at a dose of 20\\u200amg/kg/day. Lung injury degree and the protective effects of simvastatin against LPS-induced lung injury were assessed at the time-points of 24, 48 and 72\\u200ah post-injection. Serum alanine transaminase (ALT), serum creatinine (Scr) were identified to assess the hepatic and renal side-effects of simvastatin.', 'LPS inhibited the cytoskeletal regulating proteins of Cdc42 and PAK4, and was accompanied by an increased circulating endothelial microparticles (EMPs) level. The adherent junction (AJ) protein of VE-cadherin was also decreased by LPS, and was accompanied by a thickening alveolar wall, increased lung W/D values and high albumin concentration in bronchoalveolar lavage (BAL). Protective effects of simvastatin against LPS-induced lung injury were illustrated by regulating and stabilizing cytoskeletons, as well as intercellular AJs. The values of ALT and Scr were all lower than the common upper limits according to assay kits.",
            "output": [
                "Does simvastatin attenuate Acute Lung Injury Via Regulating Cdc42-PAK4 and Endothelial Microparticles?"
            ]
        },
        {
            "id": "task847-938b1159b2c34fecbc4330f7404f6cc3",
            "input": "To demonstrate the role of RpoE during the later stage of hyperosmotic stress in Salmonella.', 'Expressions of SPI-1 and SPI-2 under hyperosmotic stress for 120 min were investigated by a microarray, and the invasion and intracellular survival of wild-type and \u0394rpoE strains were compared. The global differential expression of bacterial proteins between the wild-type and \u0394rpoE strains was examined after 120 min of hyperosmotic stress.', 'SPI-1 and SPI-2 were repressed, and the invasion and intracellular survival were defected in the \u0394rpoE strain. Thirteen bacterial-associated proteins and 11 secreted proteins differed significantly between the wild-type and \u0394rpoE strains.",
            "output": [
                "Does rpoE promote invasion and intracellular survival by regulating SPI-1 and SPI-2 in Salmonella enterica serovar Typhi?"
            ]
        },
        {
            "id": "task847-0e3f98b5b8fe4863a54c82ce80c04794",
            "input": "Minor neurological dysfunction (MND) is present in one quarter to one third of children born very preterm (VP). The more severe form, complex (c)-MND has been associated with learning disabilities, behavioural and motor problems.', 'To study the association between c-MND and neurocognitive and motor disabilities at age five in VP children without CP.', 'Ninety-four children born with gestational age<30weeks and/or a birth weight<1000g were assessed at five years corrected age. MND was classified according to Touwen. The Wechsler Preschool and Primary School Scale of Intelligence (WPPSI-III-NL) was used to measure intelligence. Simple reaction time, focused attention and visuomotor coordination were measured using the Amsterdam Neuropsychological Tasks, and working memory using a Digit Span Task. For motor skills the Movement Assessment Battery for children (M-ABC2) was used.', \"Eighty-one percent was classified as 'normal' (no or simple (s-)-MND) and 19% as 'abnormal'(c-MND or mild CP). The abnormal group had a significantly lower processing speed quotient (PSQ), M-ABC percentile score and slower simple Reaction Time than the normal group. Verbal IQ, Performance IQ, working memory, focused attention and visuomotor coordination did not differ between groups. Exclusion of the mild CP cases (n=4) led to similar results.",
            "output": [
                "Is minor neurological dysfunction in five year old very preterm children associated with lower processing speed?"
            ]
        },
        {
            "id": "task847-3fa41cc2f8a14f34a7b736650aa2ffb0",
            "input": "To increase the Zn level in shoots, AtHMA4 was ectopically expressed in tomato under the constitutive CaMV 35S promoter. However, the Zn concentration in the shoots of transgenic plants failed to increase at all tested Zn levels in the medium. Modification of Zn root/shoot distribution in tomato expressing 35S::AtHMA4 depended on the concentration of Zn in the medium, thus indicating involvement of unknown endogenous metal-homeostasis mechanisms. To determine these mechanisms, those metal-homeostasis genes that were expressed differently in transgenic and wild-type plants were identified by microarray and RT-qPCR analysis using laser-assisted microdissected RNA isolated from two root sectors: (epidermis\\u2009+\\u2009cortex and stele), and leaf sectors (upper epidermis\\u2009+\\u2009palisade parenchyma and lower epidermis\\u2009+\\u2009spongy parenchyma).', 'Zn-supply-dependent modification of Zn root/shoot distribution in AtHMA4-tomato (increase at 5\\xa0\u03bcM Zn, no change at 0.5\\xa0\u03bcM Zn) involved tissue-specific, distinct from that in the wild type, expression of tomato endogenous genes. First, it is suggested that an ethylene-dependent pathway underlies the detected changes in Zn root/shoot partitioning, as it was induced in transgenic plants in a distinct way depending on Zn exposure. Upon exposure to 5 or 0.5\\xa0\u03bcM Zn, in the epidermis\\u2009+\\u2009cortex of the transgenics\\' roots the expression of the Strategy I Fe-uptake system (ethylene-dependent LeIRT1 and LeFER) was respectively lower or higher than in the wild type and was accompanied by respectively lower or higher expression of the identified ethylene genes (LeNR, LeACO4, LeACO5) and of LeChln. Second, the contribution of LeNRAMP2 expression in the stele is shown to be distinct for wild-type and transgenic plants at both Zn exposures. Ethylene was also suggested as an important factor in a pathway induced in the leaves of transgenic plants by high Zn in the apoplast, which results in the initiation of loading of the excess Zn into the mesophyll of \"Zn accumulating cells\".",
            "output": [
                "Does engineering high Zn in tomato shoot through expression of AtHMA4 involves tissue-specific modification of endogenous genes?"
            ]
        },
        {
            "id": "task847-7f91d2273a31434a9befde9a921e7283",
            "input": "Benign esophageal strictures are frequently encountered pathologies occurring due to various reasons. Repeated dilatations may be needed, particularly in resistant strictures. This study aimed to evaluate patients who underwent repeated dilatations in our clinic due to resistant esophageal strictures.', 'Sixteen patients who underwent multiple dilatations in our clinic with the diagnosis of resistant benign esophageal stricture between 2007 and 2014 were studied for age, sex, etiology, symptoms, complications, number of dilatations, and intervals between dilatations. Under general anesthesia, all patients underwent dilatation with Savary-Gilliard bougie dilators with the help of rigid esophagoscopy.', 'In 10 of the patients, stenosis was cervical, and in others it was in the thoracic esophagus. The mean dilatation performance was 4.4 (range: 3-12). In 9 patients, dilatations were performed when the patients presented with the complaint of dysphagia. Following the initial dilatation performed for dysphagia, 7 patients underwent endoscopy and dilatation 3-5 times with 1-week intervals without waiting for the development of dysphagia symptoms. These patients developed no complications, and no stenting was needed. In 5 patients, restenosis developed despite multiple dilatations, and esophageal stent placement was performed.",
            "output": [
                "Is recurrent dilatation in resistant benign esophageal strictures : timing significant?"
            ]
        },
        {
            "id": "task847-21d8517fa2144e3989c753bf5e2e01c5",
            "input": "The incidence and predictors of spontaneous hepatitis B surface-antigen (HBsAg) seroclearance in patients with chronic hepatitis B virus (HBV) were evaluated.', 'A total of 1427 patients with chronic HBV infection, who were followed between 1994 and 2013, were investigated in this retrospective study. All data were extracted from patient files.', 'Spontaneous HBsAg seroclearance occurred in 84 patients during 8798 person-years of follow-up. The patients were categorized into 3 groups at follow-up based on HBV DNA features as continuously <100 copies/mL (Group A), 0-10,000 copies/mL (Group B), and 0 to >10,000 copies/mL (Group C). Alanine aminotransferase features in the 2 groups were categorized as continuously normal (<40 U/L) and 0 to >40 U/L. Spontaneous HBsAg seroclearance was seen primarily in patients with Group A HBV DNA features, and continuously low HBV DNA values were the main predictor of HBsAg seroclearance (P < 0.001).",
            "output": [
                "Is a persistently low HBV DNA level a predictor of spontaneous HBsAg clearance in patients with chronic hepatitis B?"
            ]
        },
        {
            "id": "task847-93e763e02e534281a0074439327d214c",
            "input": "Cognitive capabilities in childhood and in late life are inversely associated with mortality rates. However, it is unclear if adult cognition, at a time still relatively free from comorbidity, is associated with subsequent mortality, and whether this explains the associations of early life factors with adult mortality.', 'We used data from the MRC National Survey of Health and Development, a birth cohort study prospectively assessing 5362 participants born in 1946. The present analysis includes participants followed up from age 43 and undergoing cognitive assessment (verbal memory and search speed). Mortality outcomes were notified through linkage with a national register. Cox regression was used to estimate mortality hazards in relation to cognitive performance at age 43, adjusting for early life factors, socioeconomic position and health status.', 'Data were available on 3192 individuals. Univariable analyses indicated that adult verbal memory and search speed, parental factors, childhood cognition and educational attainment were associated with mortality. However, multivariable models showed that the mortality associations with earlier life factors were explained by adult cognitive capability. A standard deviation increase in verbal memory and search speed scores was associated with lower mortality rates [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.77-0.97, P = 0.02; HR\\u2009=\\u20090.88, 95% CI 0.78-1.00, P = 0.05, respectively), after adjustment for adult health.",
            "output": [
                "Are verbal memory and search speed in early midlife associated with mortality over 25 years ' follow-up , independently of health status and early life factors : a British birth cohort study?"
            ]
        },
        {
            "id": "task847-fc9d7293391a42028d106ee173479fd3",
            "input": "Proton pump inhibitors (PPI) are effective at healing artificial ulcers after endoscopic submucosal dissection (ESD) for gastric neoplasms; however, the efficacy of vonoprazan is not completely understood. The aim of the present study was to determine the healing effect of vonoprazan on artificial ulcers post-gastric ESD relative to PPI.', 'Thirty-five patients who underwent gastric ESD between April and November 2015 were treated with vonoprazan 20\\xa0mg/day for 4\\xa0weeks and subsequently underwent endoscopy for evaluation of ulcer size (V group). Ulcer contraction rate was determined by the following formula: ([ESD specimen size]\\xa0-\\xa0[ulcer size at 4\\xa0weeks after ESD])/(ESD specimen size)\\xa0\u00d7\\xa0100%. We compared the results with those of a historical control group treated with esomeprazole 20\\xa0mg/day for 4\\xa0weeks after gastric ESD and subsequently measured their ulcer size (33 patients, E group) by propensity score-matching methods.', \"Sixty-two subjects were enrolled after propensity score-matching. Ulcer contraction rate at 4\\xa0weeks after ESD in the V group was significantly higher than that of the E group (97.7\\xa0\u00b1\\xa03.2% vs 94.5\\xa0\u00b1\\xa06.7%, respectively, P\\xa0=\\xa00.025). Number of subjects with a scar-stage ulcer (100% contraction rate) tended to be higher in the V group relative to the E group (32% [10 of 31] vs 13% [4 of 31], respectively, P\\xa0=\\xa00.070, McNemar's chi-squared test).",
            "output": [
                "Is vonoprazan superior to proton pump inhibitors in healing artificial ulcers of the stomach post-endoscopic submucosal dissection : A propensity score-matching analysis?"
            ]
        },
        {
            "id": "task847-a3170268d497429488fc296117370892",
            "input": "During short-term hypoxia, Hypoxia Inducible Factors (particular their subunits HIF-1\u03b1 and HIF-2\u03b1) regulate the expression of many genes including the potent angiogenesis stimulator VEGF. However, in some pathological conditions chronic hypoxia occurs and is accompanied by reduced angiogenesis.', 'We investigated the effect of prolonged hypoxia on the proliferation and sprouting ability of human microvascular endothelial cells and the involvement of the HIFs and Dll4/Notch signaling.', 'Human microvascular endothelial cells (hMVECs), cultured at 20% oxygen for 14 days and seeded on top of 3D fibrin matrices, formed sprouts when stimulated with VEGF-A/TNF\u03b1. In contrast, hMVECs precultured at 1% oxygen for 14 days were viable and proliferative, but did not form sprouts into fibrin upon VEGF-A/TNF\u03b1 stimulation at 1% oxygen. Silencing of HIF-2\u03b1 with si-RNA partially restored the inhibition of endothelial sprouting, whereas HIF-1\u03b1 or HIF-3\u03b1 by si-RNA had no effect. No involvement of Dll4/Notch pathway in the inhibitory effect on endothelial sprouting by prolonged hypoxia was found. In addition, hypoxia decreased the production of urokinase-type plasminogen activator (uPA), needed for migration and invasion, without a significant effect on its inhibitor PAI-1. This was independent of HIF-2\u03b1, as si-HIF-2\u03b1 did not counteract uPA reduction.",
            "output": [
                "Does hIF-2\u03b1 Expression regulate Sprout Formation into 3D Fibrin Matrices in Prolonged Hypoxia in Human Microvascular Endothelial Cells?"
            ]
        },
        {
            "id": "task847-a85ea7ddd48f477582e31149199539ec",
            "input": "We aimed to identify the genetic cause in a cohort of 11 unrelated cases and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD).', \"Whole-exome sequencing (n = 9), targeted resequencing (n = 4), and haplotyping were performed. Immunohistochemistry of sex-specific markers was performed on patients' gonads. The consequences of mutation were investigated using luciferase assays, localization studies, and RNA-seq.\", 'We identified a novel heterozygous NR5A1 mutation, c.274C>T p.(Arg92Trp), in three unrelated patients. The Arg92 residue is highly conserved and located in the Ftz-F1 region, probably involved in DNA-binding specificity and stability. There were no consistent changes in transcriptional activation or subcellular localization. Transcriptomics in patient-derived lymphocytes showed upregulation of MAMLD1, a direct NR5A1 target previously associated with 46,XY DSD. In gonads of affected individuals, ovarian FOXL2 and testicular SRY-independent SOX9 expression observed.",
            "output": [
                "Is nR5A1 a novel disease gene for 46 , XX testicular and ovotesticular disorders of sex development?"
            ]
        },
        {
            "id": "task847-6e19ecc6e13c4d52a4e1c3fffe72d281",
            "input": "When deciding upon the best treatment strategy in revision arthroplasty, it is absolutely crucial to use the best possible preoperative detection whether a periprosthetic joint infection (PJI) is present or not. New molecular markers investigated in serum samples and synovial fluid can help to improve the preoperative diagnosis. In 2001, a novel IL-6 lateral flow immunoassay testing device was introduced which has never been tested in synovial fluid so far.', 'For our study we investigated whether the test can be used safely, feasibly and time effectively with synovial fluid gathered from potentially infected THAs or TKAs and whether the already published cutoff for IL-6 in synovial fluid predicting a PJI can be reproduced using the QuickLine IL-6 immunoassay.', 'After ethic approval and within the scope of a prospective controlled trial we investigated 26 patients (m = 9, 34.6%; f= 17, 65.4%) with n = 13 (50%) potentially infected total hip arthroplasties (THAs) and n = 13 (50%) suspected PJIs of total knee arthroplasties (TKAs). Sterile aspirated synovial fluid was examined for total leukocyte count and cell differentiation by a blood count analyzer in body fluid mode as well as for IL-6 (Immulite, Siemens Medical Solutions Diagnostics GmbH, Eschborn, Germany). Another part of the joint aspirate was tested using the QuickLine IL-6 Test by Milenia Biotec (Milenia Biotec, Gie\u00dfen, Germany).', 'The mean concentration of IL-6 as determined from our reference laboratory testing (Siemens Immulight) for aseptic cases was 1,219 pg/mL (SD 1,369 pg/mL, min 134 pg/mL-max 4,214 pg/mL). The mean IL-6 concentration measured via the IL-6 QuickLine for aseptic cases was 410 pg/mL (SD 371 pg/mL, min 100 pg/mL-max 1562 pg/mL). The test showed no false negative or false positive results in the cases tested. In six patients, PJI was considered proven. The QuickLine Test indicated IL 6 concentrations > 10,000 pg/mL in these cases without further quantification above this maximum detection threshold. Results from the QuickLine Test and the laboratory tests were matched and a non-linear best fit curve (log-log-curve) was applied. The subsequent Spearman correlation showed a correlation coefficient of r = 0.92 (95% CI 0.81-0.97) which corresponds to a two-tailed p-value of < 0.0001, respectively. As a primary finding we were able to show that the Milenia QuickLine IL-6 Test can be used safely, feasibly and time effectively with synovial fluid gathered intraoperatively from potentially infected THAs or TKAs. The test as provided worked well in 84.6% of the samples tested and failed only due to very viscous synovial fluid. As a secondary result we found that the previously published cut-off for IL-6 in synovial fluid predicting a PJI with a sensitivity of 46.88% and a specificity of 97.62% can be reproduced using the QuickLine IL-6 immunoassay.",
            "output": [
                "Does the QuickLine IL-6 lateral flow immunoassay improve the rapid intraoperative diagnosis of suspected periprosthetic joint infections?"
            ]
        },
        {
            "id": "task847-168835669e1f461ca8f639d3d5362100",
            "input": "Evidence suggests that advance directives may improve end-of-life care among seriously ill patients, but improving completion rates remains a challenge.', 'This study tested the influence of increasing the number of options for completing an advance directive among seriously ill patients.', 'Outpatients (N = 316) receiving hemodialysis across 15 dialysis centers in the Philadelphia region between July 2014 and July 2015 were randomized to receive either the option to complete a brief advance directive form or expanded options including a brief, expanded, or comprehensive form. Patients in both groups could decline to complete an advance directive or take their selected version home. The primary outcome was a returned, completed advance directive. Secondary outcomes included whether patients wanted to complete an advance directive, decision satisfaction, quality of life at 3 months, and patient factors associated with advance directive completion.', 'Although offering more advance directive options was not significantly associated with increased rates of completion (13.1% in the standard group v. 12.2% in the expanded group, P = 0.80), it did significantly increase the proportion of patients who wanted to complete an advance directive and took one home (71.9% in standard v. 85.3% in expanded, P = 0.004). There was no difference in satisfaction (P = 0.65) or change in quality of life between groups (P = 0.63). A higher baseline quality of life was independently associated with advance directive completion (P = 0.006).",
            "output": [
                "Does a Randomized Trial of Expanding Choice set to Motivate Advance Directive Completion?"
            ]
        },
        {
            "id": "task847-28e323c314524d139f6bb491aa44d449",
            "input": "Although race is associated with prostate cancer progression in early stage disease, once men have advanced disease, it is unclear whether race continues to predict a poor outcome. The authors hypothesized that, in an equal-access setting among patients with castration-resistant prostate cancer (CRPC) and no known metastases (M0/Mx), black men would receive imaging tests at similar rates as nonblack men (ie, there would be an equal opportunity to detect metastases) but would have a higher risk of metastatic disease.', 'In total, 837 men who were diagnosed with M0/Mx CRPC during 2000 through 2014 from 5 Veterans Affairs hospitals in the SEARCH (Shared Equal Access Regional Cancer Hospital) database were analyzed. Data on all imaging tests after CRPC diagnosis were collected, including date, type, and outcome. Multivariable Cox models were used to test associations between race and the time to first metastasis, first bone metastasis, first bone scan, second bone scan among men who had a negative first bone scan, and overall survival.', 'Black men (n\\u2009=\\u2009306) were equally as likely as nonblack men (n\\u2009=\\u2009531) to receive a first and second bone scan after a diagnosis of CRPC. There were no significant differences in the risk of developing any metastases, bone metastases, time to bone scans, or overall survival between black men and nonblack men (all P\\u2009>\\u2009.2).",
            "output": [
                "Does race predict the development of metastases in men with nonmetastatic castration-resistant prostate cancer?"
            ]
        },
        {
            "id": "task847-e199da6511054f558df9e67c0792fd16",
            "input": "Dyschloremia is common in critically ill patients, although its impact has not been well studied. We investigated the epidemiology of dyschloremia and its associations with the incidence of acute kidney injury and other intensive care unit outcomes.', 'This is a single-center, retrospective cohort study at Mayo Clinic Hospital-Rochester. All adult patients admitted to intensive care units from January 1st, 2006, through December 30th, 2012 were included. Patients with known acute kidney injury and chronic kidney disease stage 5 before intensive care unit admission were excluded. We evaluated the association of dyschloremia with ICU outcomes, after adjustments for the effect of age, gender, Charlson comorbidity index and severity of illness score.', 'A total of 6,025 patients were enrolled in the final analysis following the implementation of eligibility criteria. From the cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney injury was higher in hypochloremic and hyperchloremic patients compared to those with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P < .001). Baseline serum chloride was lower in the acute kidney injury group vs. the non-acute kidney injury group [100 mmol/L (96-104) vs. 102 mmol/L (98-105), P < .0001]. In a multivariable logistic regression model, baseline serum chloride of \u226494 mmol/L found to be independently associated with the risk of acute kidney injury (OR 1.7, 95% CI 1.1-2.6; P = .01).",
            "output": [
                "Does dyschloremia be a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients?"
            ]
        },
        {
            "id": "task847-c50d43234fa749cabd0f8f5ece1a650d",
            "input": "Ginsenoside Rd (GSRd), one of the main active ingredients in traditional Chinese herbal Panax ginseng, has been found to have therapeutic effects on ischemic stroke. However, the molecular mechanisms of GSRd's neuroprotective function remain unclear. Ischemic stroke-induced oxidative stress results in DNA damage, which triggers cell death and contributes to poor prognosis. Oxidative DNA damage is primarily processed by the base excision repair (BER) pathway. Three of the five major DNA glycosylases that initiate the BER pathway in the event of DNA damage from oxidation are the endonuclease VIII-like (NEIL) proteins. This study aimed to investigate the effect of GSRd on the expression of DNA glycosylases NEILs in a rat model of focal cerebral ischemia.\", 'NEIL expression patterns were evaluated by quantitative real-time polymerase chain reaction in both normal and middle cerebral artery occlusion (MCAO) rat models. Survival rate and Zea-Longa neurological scores were used to assess the effect of GSRd administration on MCAO rats. Mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damages were evaluated by the way of real-time analysis of mutation frequency. NEIL expressions were measured in both messenger RNA (mRNA) and protein levels by quantitative polymerase chain reaction and Western blotting analysis. Apoptosis level was quantitated by the expression of cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling assay.', 'We found that GSRd administration reduced mtDNA and nDNA damages, which contributed to an improvement in survival rate and neurological function; significantly up-regulated NEIL1 and NEIL3 expressions in both mRNA and protein levels of MCAO rats; and reduced cell apoptosis and the expression of cleaved caspase-3 in rats at 7 days after MCAO.",
            "output": [
                "Does ginsenoside Rd attenuate DNA Damage by Increasing Expression of DNA Glycosylase Endonuclease VIII-like Proteins after Focal Cerebral Ischemia?"
            ]
        },
        {
            "id": "task847-a28aebb4e3df40b3bff382e4ee7b5d5c",
            "input": "Acute myocardial infarction (AMI) is commonly known as the heart attack. The molecular events involved in the development of AMI remain unclear. This study was to investigate the expression of miR-103a in patients with high blood pressure (HBP) and AMI patients with and without HBP, as well as its effect on endothelial cell functions.', 'MiR-103a expression in plasma and peripheral blood mononuclear cells was measured by real-time polymerase chain reaction (PCR). The regulatory effect of miR-103a on Piezo1 gene was identified by a luciferase reporter system. The role of miR-103a in endothelial cells was evaluated by the capillary tube formation ability and cell viability of human umbilical vein endothelial cells (HUVECs).', 'The plasma miR-103a concentration was significantly elevated in patients with HBP alone, AMI alone, and comorbidity of AMI and HBP. The miR-103a expression in peripheral blood mononuclear cells (PBMCs) in patients with AMI and HBP was significantly higher than the one in healthy controls (p < 0.05), however miR-103a expression in PBMCs was not significantly different among patients with HBP alone, patients with AMI alone, and healthy controls. MiR-103a targeted Piezo1 and inhibited Piezo1 protein expression, which subsequently reduced capillary tube formation ability and cell viability of HUVECs.",
            "output": [
                "Is miR-103a targeting Piezo1 involved in acute myocardial infarction through regulating endothelium function?"
            ]
        },
        {
            "id": "task847-a256bd25924c4b8e93faafd15ca5a687",
            "input": "The aim was to determine the feasibility of a six-week speed-based exercise program that could be used to initiate new exercise behaviors and improve rapid movement in older adults approaching frailty.', 'The intervention group included 14 older adults (3 males, 11 females, mean (SD) age: 70 (7.6) years, height: 1.6 (.11) m, mass: 76.8 (12.0) kg, BMI: 27.7(4.7)). The control group included 12 older adults (6 males, 6 females, mean (SD) age: 69.2 (6.9) years, height: 1.7 (.09) m, mass: 78.2 (10.9) kg, BMI: 25.3 (2.7)). Subjects included active older adults, including regular exercisers, but none were engaged in sports or exercises with an emphasis on speed (e.g. cycling spin classes or tennis). Stationary recumbent cycling was selected to minimize fall risk and low pedaling resistance reduced musculoskeletal and cardiovascular load. Two weekly 30-minute exercise sessions consisted of interval training in which subjects pedaled at preferred cadence and performed ten 20-s fast cadence intervals separated by 40-s of active recovery at preferred cadence.', 'Significant Group by Time interactions (p<.05) supported a 2-s improvement in the timed up and go test and a 34% improvement in rapid isometric knee extension contractions in the exercise group but not in controls. Central neural adaptations are suggested because this lower extremity exercise program also elicited significant improvements in the untrained upper extremities of the exercise group (elbow extension RFD-SF and 9-Hole Peg Test, p<.05).",
            "output": [
                "Does high-Speed Cycling Intervention improve Rate-Dependent Mobility in Older Adults?"
            ]
        },
        {
            "id": "task847-a1d50945d93a4034939320f33e18889b",
            "input": "Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with subclinical cardiovascular damage and cardiovascular events. Whether suPAR is of prognostic value in asymptomatic patients with aortic stenosis (AS) remains unknown.', 'Plasma suPAR levels were measured in 1503 patients with a mean age of 68 years who were recruited in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression analysis was performed to evaluate associations between suPAR and the composite end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs), cardiovascular and all-cause mortality after adjusting for traditional cardiovascular risk factors, and allocation to treatment.', 'The multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P\\xa0= 0.002 for ICEs; HR, 1.2; 95% CI, 0.9-1.5; P\\xa0= 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P\\xa0= 0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for all-cause mortality.",
            "output": [
                "Does suPAR predict Cardiovascular Events and Mortality in Patients With Asymptomatic Aortic Stenosis?"
            ]
        },
        {
            "id": "task847-ed4d3534357a4056b1a00f1f2aa53463",
            "input": "Tobacco smoking is a public health issue and has been implicated in adverse reproductive outcomes including semen quality. Available data however provides conflicting findings. The objective of this study was to evaluate the effect of tobacco smoking on semen quality among men in Ghana.', 'In this study, a total of 140 subjects were recruited, comprising 95 smokers and 45 non-smokers. Smokers were further categorized into mild, moderate and heavy smokers. Semen parameters such as sperm concentration, motility, viability and normal morphology were measured according to the World Health Organisation criteria.', 'The study showed that smokers had significantly lower semen volume, sperm concentration, sperm motility, total sperm count, sperm morphology, free testosterone and follicle stimulating hormone (p <0.05 respectively), compared with non-smokers. Smokers were at a higher risk of developing oligospermia, asthenozoospermia and teratozoospermia (OR\\u2009=\\u20093.1, 4.2 and, 4.7; p <0.05) than non-smokers.",
            "output": [
                "Is tobacco smoking associated with decreased semen quality?"
            ]
        },
        {
            "id": "task847-ad7a26da23dd4bb8bf168759246a4e88",
            "input": "Mammalian circadian rhythms regulate many metabolic processes. Recent studies suggest that brain and muscle Arnt-like 1 (BMAL1), an important component of mammalian circadian rhythm, is associated with insulin signaling. Several studies have shown that insulin is associated with bone metabolism; however, the relationship between BMAL1 and osteoblasts remains unclear.', 'Expression of osteogenic markers and Bmal1 in MC3T3-E1 cells was measured by RT-PCR and Western blotting. Alizarin red S staining was performed to assess matrix mineralization in MC3T3-E1 cells.', 'mRNA levels of osteogenic genes and Bmal1 were up-regulated in MC3T3-E1 cells upon insulin treatment. In addition, Bmal1 overexpression increased the expression of osteogenic genes including inhibitor of DNA binding (Id1), Runt-related transcription factor 2 (Runx2), and osteocalcin (OC). Interestingly, expression of Bone morphogenetic protein-2 (BMP2), an important upstream factor of Id1, Runx2, and OC, was markedly increased by Bmal1. Finally, we confirmed that insulin-induced BMP2 expression was attenuated in Bmal1 knockout (KO) cells. PCR analysis and alizarin red S staining showed that insulin-mediated increases gene expression and calcium deposition were reduced in Bmal1 KO cells compared to wild-type cells.",
            "output": [
                "Does bmal1 induce osteoblast differentiation via regulation of BMP2 expression in MC3T3-E1 cells?"
            ]
        },
        {
            "id": "task847-3fa1e79fb8b34c6a8dc1e214f307216b",
            "input": "Given the high prevalence of obesity and noncommunicable diseases in Mexico and the key role of dietary quality in these conditions, it is important to determine Mexicans' adherence to dietary recommendations.\", 'Our aim was to estimate the percentage of the Mexican population who adhere to dietary recommendations for key food groups.', 'We analyzed 7983 participants aged \u22655 y from the nationally representative Mexican National Health and Nutrition Survey 2012. Dietary intake data were collected by using one 24-h recall and a repeated 24-h recall in 9% of the sample. We used the National Cancer Institute method for episodically consumed foods, which uses a 2-part (probability and amount) mixed regression model to estimate the usual intake distribution and its association with sociodemographic variables.', 'For the food groups that are encouraged, only 1-4% of the population (range across sex and age groups) reached the recommended intake of legumes, 4-8% for seafood, 7-16% for fruit and vegetables, and 9-23% for dairy. For food groups that are discouraged, only 10-22% did not exceed the recommended upper limit for sugar-sweetened beverages, 14-42% for high saturated fat and/or added sugar (HSFAS) products, and 9-50% for processed meats, whereas the majority (77-93%) did not exceed the limit for red meat. A lower proportion of adolescents than children and adults adhered to recommendations for several food groups. Participants with higher socioeconomic status (SES) and living in urban areas consumed more (probability of consuming and/or amount consumed) fruit and vegetables, dairy, and HSFAS products, but they consumed fewer legumes than those of lower SES and living in rural areas.",
            "output": [
                "Does adherence to Dietary Recommendations for Food Group Intakes be Low in the Mexican Population?"
            ]
        },
        {
            "id": "task847-c6bb08f7204a407f8ec1917b6666f736",
            "input": "To assess the role of whole-body computed tomography (CT) for determining morphological suitability before multiorgan retrieval (MOR) in brain dead patients.', 'Fifty-one clinically brain dead patients (21 women, 30 men; mean age 61 year\u00b115) were included in this prospective, single center study. All patients had CT angiography of the brain and whole-body CT examination. CT images were evaluated for the presence of morphological abnormalities of lungs, liver and other abdominal organs and presence of vascular anatomical variants. The results of CT examinations were compared to intraoperative findings observed during organ harvesting and/or the results of histopathological analysis of biopsy specimens. The impact of whole-body CT examination on the harvesting process was evaluated.', 'Ninety-five percent of vascular anatomical variants that were found intraoperatively were depicted on CT. CT density measurements predicted surgical finding of steatosis in 80% of patients. Whole-body CT changed the MOR strategy in 21/51 patients (41%) including 3 MOR cancellations and 8 grafts refusals, whereas organ harvesting was continued in 10 patients after histopathological analysis was performed.",
            "output": [
                "Is simultaneous CT angiography and whole-body CT an effective imaging approach before multiorgan retrieval?"
            ]
        },
        {
            "id": "task847-c9296dd45af8442d9aa6b264bb764624",
            "input": "After the introduction of the Biotronik Linox S/SD high-voltage lead, several cases of early failure have been observed.', 'The purpose of this article was to assess the performance of the Linox S/SD lead in comparison to 2 other contemporary leads.', 'We used the prospective Erasmus MC ICD registry to identify all implanted Linox S/SD (n = 408), Durata (St. Jude Medical, model 7122) (n = 340), and Endotak Reliance (Boston Scientific, models 0155, 0138, and 0158) (n = 343) leads. Lead failure was defined by low- or high-voltage impedance, failure to capture, sense or defibrillate, or the presence of nonphysiological signals not due to external interference.', 'During a median follow-up of 5.1 years, 24 Linox (5.9%), 5 Endotak (1.5%), and 5 Durata (1.5%) leads failed. At 5-year follow-up, the cumulative failure rate of Linox leads (6.4%) was higher than that of Endotak (0.4%; P < .0001) and Durata (2.0%; P = .003) leads. The incidence rate was higher in Linox leads (1.3 per 100 patient-years) than in Endotak and Durata leads (0.2 and 0.3 per 100 patient-years, respectively; P < .001). A log-log analysis of the cumulative hazard for Linox leads functioning at 3-year follow-up revealed a stable failure rate of 3% per year. The majority of failures consisted of noise (62.5%) and abnormal impedance (33.3%).",
            "output": [
                "Does comparative study of the failure rates among 3 implantable defibrillator lead?"
            ]
        },
        {
            "id": "task847-6561f1b730c048d083541dcf84eadd91",
            "input": "Although the common, silver, and bighead carps are native and sparsely distributed in Eurasia, these fish have become abundant and invasive in North America. An understanding of the biology of these species may provide insights into sustainable control methods. The animal-associated microbiome plays an important role in host health. Characterization of the carp microbiome and the factors that affect its composition is an important step toward understanding the biology and interrelationships between these species and their environments.', 'We compared the fecal microbiomes of common, silver, and bighead carps from wild and laboratory environments using Illumina sequencing of bacterial 16S ribosomal RNA (rRNA). The fecal bacterial communities of fish were diverse, with Shannon indices ranging from 2.3 to 4.5. The phyla Proteobacteria, Firmicutes, and Fusobacteria dominated carp guts, comprising 76.7\\xa0% of total reads. Environment played a large role in shaping fecal microbial community composition, and microbiomes among captive fishes were more similar than among wild fishes. Although differences among wild fishes could be attributed to feeding preferences, diet did not strongly affect microbial community structure in laboratory-housed fishes. Comparison of wild- and lab-invasive carps revealed five shared OTUs that comprised approximately 40\\xa0% of the core fecal microbiome.",
            "output": [
                "Does environment shape the fecal microbiome of invasive carp species?"
            ]
        },
        {
            "id": "task847-728592b848fd4369bc5ab3462657da59",
            "input": "Postoperative pancreatic fistula (POPF) is a life-threatening complication after pancreaticoduodenectomy (PD). The aim of this study is to evaluate the significance of pancreatic amylase level of pancreatic juice for PF after PD.', 'The subjects were 46 patients who underwent PD between January 2012 and August 2015 at Jikei University Hospital. We retrospectively investigated the relation between patient characteristics including pancreatic amylase level of pancreatic juice through the pancreatic drainage tube and the incidence of POPF (grade B or grade C according to the International Study Group on the Pancreatic Fistula) using univariate and multivariate analyses. The decline of pancreatic amylase level of pancreatic juice was evaluated by 1 - postoperative day 3/postoperative day 1 ratio.', 'In univariate analysis, nonductal adenocarcinoma (P = 0.0252), soft pancreatic remnant (P = 0.0155), and decline of pancreatic amylase level of pancreatic juice \u2265 80% (P = 0.0010) were significant predictors of POPF. In multivariate analysis, decline of pancreatic amylase level of pancreatic juice of 80% or greater (P = 0.0192) was the only significant independent parameter.",
            "output": [
                "Does the Decline of Amylase Level of Pancreatic Juice After Pancreaticoduodenectomy predict Postoperative Pancreatic Fistula?"
            ]
        },
        {
            "id": "task847-c90d875aa490423c9a8f4863b719f7ec",
            "input": "Performance status [Eastern Cooperative Oncology Group (ECOG)] is a physician-assigned score indicating a patient's fitness for treatment. Functional assessment of cancer therapy-esophagus (FACT-E) is a patient-reported, health-related quality-of-life (HRQOL) instrument containing an oesophageal cancer subscale (ECS). Our objective was to assess the discriminative ability of pretreatment FACT-E and ECS when compared with performance status in predicting survival in patients with Stage II-III oesophageal cancer.\", 'Patient data from four prospective studies were pooled together. These four studies included oesophageal patients who received chemoradiation either as neoadjuvant therapy or as definitive therapy. Three separate Cox regressions were performed considering FACT-E, ECS and ECOG as the main predictors, respectively. Receiver-operating characteristics analyses were performed.', 'Of the 120 curative intent patients, 39.8% (n = 51), 58.6% (n = 75) and 1.6% (n = 2) had ECOG 0, 1 and 2, respectively. On Cox regression analysis, pretreatment FACT-E (P = 0.04) and ECS (P = 0.004) but not ECOG (P = 0.27) were independently associated with overall survival. ECOG could not discriminate between survivors and non-survivors (P = 0.28) with an area under the curve (AUC) of 0.56 [95% confidence interval (CI): 0.45-0.66], whereas FACT-E (P = 0.02) and ECS (P < 0.001) were discriminative with AUC = 0.63 (95% CI: 0.52-0.73) and AUC = 0.69 (95% CI: 0.60-0.79), respectively.",
            "output": [
                "Is pretreatment quality-of-life score a better discriminator of oesophageal cancer survival than performance status?"
            ]
        },
        {
            "id": "task847-f0b775b83e7f458c9ec7f52cbb1acd85",
            "input": "Harris Health System (HHS) is a safety net system providing health care to the underserved of Harris County, Texas. There was a 6-month waiting period for a rheumatologist consult for patients with suspected systemic lupus erythematosus (SLE). The objective of the intervention was to improve access to specialty care.', 'An algorithmic approach to testing for SLE was implemented initially through the HHS referral center. The algorithm was further offered as a \"one-click\" order for physicians, with automated reflex testing, interpretation, and case triaging by clinical pathology.', 'Data review revealed that prior to the intervention, 80% of patients did not have complete laboratory workups available at the first rheumatology visit. Implementation of algorithmic testing and triaging of referrals by pathologists resulted in decreasing the waiting time for a rheumatologist by 50%.",
            "output": [
                "Does algorithmic Approach With Clinical Pathology Consultation improve Access to Specialty Care for Patients With Systemic Lupus Erythematosus?"
            ]
        },
        {
            "id": "task847-1f6896f4e7bc48369fa052e7959cb39c",
            "input": "Small studies suggest exogenous estrogen may improve vitamin D status, but the etiology is unclear because women who use hormones may make lifestyle choices that differentially affect vitamin D status.', 'Our objective was to investigate the association between use of hormonal contraception and 25-hydroxy-vitamin D (25(OH)D).', 'We used linear regression modeling of cross-sectional data to estimate percent change in season-adjusted serum 25(OH)D with estrogen use after adjustment for other factors.', 'At the enrollment clinic visit (2010-2012) into a cohort study of uterine fibroids, each subject provided a blood sample, had anthropomorphic variables and skin reflectance measured, and answered questionnaires on demographics, dietary and supplement intake, contraceptive use, reproductive and medical history, and behaviors.', 'A total of 1662 African American women, community volunteers, 23-34 years old, living in the Detroit, Michigan, area were included.', 'None.', 'Serum 25(OH)D was measured.', 'Serum 25(OH)D concentrations were low (70% <20 ng/ml). Current use of an estrogen-containing contraceptive was associated with a 20% (95% confidence interval: 14-27) increase in 25(OH)D after adjustment. There was no increase in 25(OH)D among participants who had used estrogen in the past, but were not current users, indicating that results were unlikely to be due to unmeasured confounding by factors related to contraceptive choice.",
            "output": [
                "Does use of Estrogen-Containing Contraception be Associated With Increased Concentrations of 25-Hydroxy Vitamin D?"
            ]
        },
        {
            "id": "task847-7fde56b1b11f475d84d8d53465cd1253",
            "input": "The objective of the study was to investigate the splanchnic blood flow velocity and oximetry response to blood transfusion in preterm infants according to postnatal age.', 'Preterm infants receiving blood transfusion were recruited to three groups: 1-7 (group 1; n = 20), 8-28 (group 2; n = 21) and \u226529 days of life (group 3; n = 18). Superior mesenteric artery (SMA) peak systolic (PSV) and diastolic velocities were measured 30-60 min pre- and post-transfusion using Doppler ultrasound scan. Splanchnic tissue haemoglobin index (sTHI), tissue oxygenation index (sTOI) and fractional tissue oxygen extraction (sFTOE) were measured from 15-20 min before to post-transfusion using near-infrared spectroscopy.', 'The mean pretransfusion Hb in group 1, 2 and 3 was 11, 10 and 9 g/dl, respectively. The mean (SD) pretransfusion SMA PSV in group 1, 2 and 3 was 0\u00b763 (0\u00b732), 0\u00b781 (0\u00b733) and 0\u00b797 (0\u00b740) m/s, respectively, and this did not change significantly following transfusion. The mean (SD) pretransfusion sTOI in group 1, 2 and 3 was 36\u00b77 (19\u00b73), 44\u00b76 (10\u00b74) and 41\u00b73 (10\u00b74)%, respectively. The sTHI and sTOI increased (P < 0\u00b701), and sFTOE decreased (P < 0\u00b701) following transfusion in all groups. On multivariate analysis, changes in SMA PSV and sTOI following blood transfusion were not associated with PDA, feeding, pretransfusion Hb and mean blood pressure.",
            "output": [
                "Does blood transfusion in preterm infants improve intestinal tissue oxygenation without alteration in blood flow?"
            ]
        },
        {
            "id": "task847-566c51f047964e8a8e08e6c69354f427",
            "input": "the use of antihypertensive medication in older people in order to prevent cardiovascular events is well established. The use of such agents has been encouraged by incentive schemes in the United Kingdom including the Quality and Outcomes Framework. In addition, many guidelines recommend good blood pressure (BP) control in the elderly. However, in older people antihypertensives can cause adverse effects related to hypotension.', 'the aim of this study was to assess the prevalence of low\\xa0BP and impact on outcomes, particularly in the presence of antihypertensive treatment, in a primary care population of older people.', 'a retrospective observational cohort study in people over the age of 70 years registered with primary care providers in Kent.', 'a total of 11,167 patients over 70 years old were analysed, 6,373 female (57%). Systolic blood pressure (SBP) was below 120 mmHg in 1,297 people (844 on antihypertensives), below 110 mmHg in 474 (313 on antihypertensives) and below 100 mmHg in 128 (89 on antihypertensives). Hypotension was independently associated with mortality, acute kidney injury and hospital admission.",
            "output": [
                "Do older people remain on blood pressure agents despite being hypotensive resulting in increased mortality and hospital admission?"
            ]
        },
        {
            "id": "task847-b876a5535cdb4111a0cf2599f4b1b06c",
            "input": "Lung volume and pulmonary blood flow decrease in patients with interstitial lung disease (ILD). The purpose of this study was to assess the relationship between pulmonary blood flow and lung volume in ILD patients.', \"This research was approved by the institutional review board. Twenty-seven patients (9 men, 18 women; mean age, 59 years; range, 24-79 years) with ILD were included. Blood flow was assessed in the pulmonary trunk and the left and right pulmonary arteries by phase contrast magnetic resonance imaging (MRI). Lung volume and the computed tomography (CT) visual score that indicates the severity of ILD were assessed on the left and right sides by thin-section CT scanning. Lung volume was automatically measured by lung analysis software (VINCENT Ver. 4). The CT visual score was measured by averaging the proportion of abnormal lung area at five anatomic levels. Pearson's correlation coefficient was used to determine the relationship between pulmonary blood flow and lung volume.\", 'Pulmonary blood flow showed a significant correlation with lung volume (both: r=0.52, p=0.006; left: r=0.61, p=0.001; right: r=0.54, p=0.004) and CT visual score (both: r=-0.39, p=0.04; left: r=-0.48, p=0.01; right: r=-0.38, p=0.04). Partial correlation analysis, controlled for age, height and weight, showed a significant correlation between pulmonary blood flow and lung volume (both: r=0.43, p=0.03; left: r=0.55, p=0.005; right: r=0.48, p=0.01) and CT visual score (both: r=-0.58, p=0.003; left: r=-0.51, p=0.01; right: r=-0.64, p=0.001).",
            "output": [
                "Is decrease of pulmonary blood flow detected by phase contrast MRI correlated with a decrease in lung volume and increase of lung fibrosis area determined by computed tomography in interstitial lung disease?"
            ]
        },
        {
            "id": "task847-ab0ff77494814f02aa3df9df8735fb33",
            "input": "Two-stage revision surgery for infected total hip arthroplasty (THA) is commonly advocated, but substantial morbidity and expense are associated with this technique. In certain cases of infected THA, treatment with one-stage revision surgery and intraarticular infusion of antibiotics may offer a reasonable alternative with the distinct advantage of providing a means of delivering the drug in high concentrations.', 'We describe a protocol for intraarticular delivery of antibiotics to the hip through an indwelling catheter combined with one-stage revision surgery and examine (1) the success as judged by eradication of infection at 1 year when treating chronically infected cemented stems; (2) success in treating late-onset acute infections in well-ingrown cementless stems; and (3) what complications were associated with this approach in a small case series.', \"Between January 2002 and July 2013, 30 patients (30 hips) presented to the senior author for treatment of infected THA. Of those, 21 patients (21 hips) with infected cemented THAs underwent d\u00e9bridement and single-stage revision to cementless total hip implants followed by catheter infusion of intraarticular antibiotics. Nine patients (nine hips) with late-onset acute infections in cementless THA had bone-ingrown implants. These patients were all more than 2 years from their original surgery and had acute symptoms of infection for 4 to 9 days. Seven had their original THA elsewhere, and two were the author's patients. All were symptom-free until the onset of their infection, and none had postoperative wound complications, fever, or prolonged pain suggestive of a more chronic process. They were treated with d\u00e9bridement and head and liner exchange, again followed by catheter infusion of intraarticular antibiotics. During this time period, this represented all infected THAs treated by the senior author, and all were treated with this protocol; no patient underwent two-stage exchange during this time, and no patients were lost to followup. At the time of the surgery, two Hickman catheters were placed in each hip to begin intraarticular delivery of antibiotics in the early postoperative period. Antibiotics were infused daily into the hip for 6 weeks with the tubes used for infusion only. Eleven of the single-stage revisions and four of the hips treated with d\u00e9bridement had methicillin-resistant Staphylococcus aureus. Patients were considered free of infection if they had no clinical signs of infection and had a normal C-reactive protein and erythrocyte sedimentation rate at 1 year. Complications were ascertained by chart review.\", 'Twenty of 21 (95%) infections in patients who had single-stage revision for chronically infected cemented THA were apparently free from infection and remained so at a mean followup of 63 months (range, 25-157 months). One case grew Candida albicans in the operative cultures and remained free of signs of infection after rerevision followed by infusion of fluconazole. The nine cementless THAs treated with d\u00e9bridement and head/liner exchange all remained free of signs of infection at a mean followup of 74 months (range, 62-121 months). Few complications were associated with the technique. Four patients had elevated serum levels of vancomycin without renal function changes and two patients had transient blood urea nitrogen/creatinine elevations with normal vancomycin levels that resolved with dosage adjustments. No patient had evidence of permanent renal damage. None of the patients in this study developed a chronic fistula or had significant drainage from the catheter site.",
            "output": [
                "Does one-stage Revision With Catheter Infusion of Intraarticular Antibiotics Successfully treat Infected THA?"
            ]
        },
        {
            "id": "task847-7dfdfa8ce3ca4a6089428af3cd58f134",
            "input": "In 1970, Breslow described his eponymously named thickness measurement. No-one has sought to enhance the Breslow thickness (BT). The aim of this study was to demonstrate a proof of concept that the density of melanoma cells at the position where the BT is measured is a morphological prognostic biomarker, which we name the Breslow density (BD). The hypothesis was that the BD has prognostic value for overall survival (OS) and is independent of the BT.', 'We analysed 100 cutaneous melanomas, and followed REMARK guidelines. The BD was the estimated percentage dermal area occupied by melanoma cells in a specified location. The BT and BD had a strong correlation (P = 2.1 \u00d7 10",
            "output": [
                "Is breslow density a novel prognostic feature in cutaneous malignant melanoma?"
            ]
        },
        {
            "id": "task847-852b865b87d143039a517106d9dbb95e",
            "input": "Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We explored whether response evaluation by magnetic resonance imaging (MRI) is associated with recurrence-free survival after NAC in ER-positive/HER2-negative breast cancer.', 'MRI examinations were performed in 272 women with ER-positive/HER2-negative breast cancer before, during and after NAC. MRI interpretation included lesion morphology at baseline, changes in morphology and size, and contrast uptake kinetics. These MRI features, clinical characteristics and final pathology were correlated with recurrence-free survival.', 'The median follow up time was 41 months. There were 35 women with events, including 19 breast-cancer-related deaths. On multivariable analysis, age younger than 50 years (hazard ratio (HR)\\u2009=\\u20092.55, 95 % confidence interval (CI) 1.3, 5.02, p\\u2009=\\u20090.007), radiological complete response after NAC (HR\\u2009=\\u200914.11, CI 1.81, 1818; p\\u2009=\\u20090.006) and smaller diameters of washout/plateau enhancement at MRI after NAC (HR\\u2009=\\u20091.02, CI 1.00, 1.04, p\\u2009=\\u20090.036) were independently associated with best recurrence-free survival. Pathological response was not significant; HR\\u2009=\\u20092.12, CI 0.86, 4.64, p\\u2009=\\u20090.096.",
            "output": [
                "Is survival associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer?"
            ]
        },
        {
            "id": "task847-40db1d757d344408bce5aa3ff87617a7",
            "input": "Systemic inflammatory response syndrome (SIRS) and sepsis are now frequently identified by observations of vital signs and detection of organ failure during triage in the emergency room. However, there is less focus on the effect on patient outcome with better observation and treatment at the ward level.', \"This was a before-and-after intervention study in one emergency and community hospital within the Mid-Norway Sepsis Study catchment area. All patients with confirmed bloodstream infection have been prospectively registered continuously since 1994. Severity of sepsis, observation frequency of vital signs, treatment data, length of stay (LOS) in high dependency and intensive care units, and mortality were retrospectively registered from the patients' medical journals.\", 'The post-intervention group (n\\u2009=\\u2009409) were observed better and had higher odds of surviving 30\\xa0days (OR 2.7, 95\\xa0% CI 1.6, 4.6), lower probability of developing severe organ failure (0.7, 95\\xa0% CI 0.4, 0.9), and on average, 3.7\\xa0days (95\\xa0% CI 1.5, 5.9\\xa0days) shorter LOS than the pre-intervention group (n\\u2009=\\u2009472).",
            "output": [
                "Does early identification of sepsis in hospital inpatients by ward nurses increase 30-day survival?"
            ]
        },
        {
            "id": "task847-18478483a760499196372194e2ab0d84",
            "input": "Recently, casein glycomacropeptide (GMP)-derived peptide was found to possess potent antioxidant and anti-inflammatory activities. In this study, the improvement effects and underlying molecular mechanisms of GMP-derived peptide on hepatic insulin resistance were investigated.', 'The peptide IPPKKNQDKTE was identified from GMP papain hydrolysates by LC-ESI-MS/MS. Effects of IPPKKNQDKTE on glucose metabolism and expression levels of the hepatic insulin signaling proteins in high glucose-induced insulin-resistant HepG2 cells were evaluated. Results showed that IPPKKNQDKTE dose-dependently increased glucose uptake and intracellular glycogen in insulin-resistant HepG2 cells without affecting cell viability. IPPKKNQDKTE increased the phosphorylation of Akt and GSK3\u03b2 and decreased the expression levels of p-GS, G6Pase and PEPCK. These IPPKKNQDKTE-mediated protection effects were reversed by PI3K/Akt inhibitor LY294002, showing the mediatory role of PI3K/Akt. Moreover, treatment with IPPKKNQDKTE reduced IRS-1 Ser307 phosphorylation and increased phosphorylation of AMPK. Knockdown AMPK using siRNA in HepG2 cells increased Ser307 phosphorylation of IRS-1 and reduced Akt phosphorylation in IPPKKNQDKTE-treated insulin-resistant cells.",
            "output": [
                "Does casein glycomacropeptide-derived peptide IPPKKNQDKTE ameliorate high glucose-induced insulin resistance in HepG2 cells via activation of AMPK signaling?"
            ]
        },
        {
            "id": "task847-20922661b3e548f7b45fa435d4f24654",
            "input": "Emerging evidence suggests that the in utero environment is not sterile as once presumed. Work in the mouse demonstrated transmission of commensal bacteria from mother to fetus during gestation, though it is unclear what modulates this process. We have previously shown in the nonhuman primate that, independent of obesity, a maternal high-fat diet during gestation and lactation persistently shapes the juvenile gut microbiome. We therefore sought to interrogate in a population-based human longitudinal cohort whether a maternal high-fat diet similarly alters the neonatal and infant gut microbiome in early life.', 'A representative cohort was prospectively enrolled either in the early third trimester or intrapartum (n\\u2009=\\u2009163), with a subset consented to longitudinal sampling through the postpartum interval (n\\u2009=\\u200981). Multiple body site samples, including stool and meconium, were collected from neonates at delivery and by 6\\xa0weeks of age. A rapid dietary questionnaire was administered to estimate intake of fat, added sugars, and fiber over the past month (National Health and Examination Survey). DNA was extracted from each infant meconium/stool sample (MoBio) and subjected to 16S rRNA gene sequencing and analysis.', \"On average, the maternal dietary intake of fat ranged from 14.0 to 55.2\\xa0%, with an average intake of 33.1\\xa0% (\u03c3\\u2009=\\u20096.1\\xa0%). Mothers whose diets significantly differed from the mean (\u00b11 standard deviation) were separated into two distinct groups, a control group (n\\u2009=\\u200913, \u03bc\\u2009=\\u200924.4\\xa0%) and a high-fat group (n\\u2009=\\u200913, \u03bc\\u2009=\\u200943.1\\xa0%). Principal coordinate analysis revealed that the microbiome of the neonatal stool at birth (meconium) clustered differently by virtue of maternal gestational diet (PERMANOVA p\\u2009=\\u20090.001). LEfSe feature selection identified several taxa that discriminated the groups, with a notable relative depletion of Bacteroides in the neonates exposed to a maternal high-fat gestational diet (Student's t-test, p\\u2009<\\u20090.05) that persisted to 6\\xa0weeks of age.",
            "output": [
                "Does the early infant gut microbiome vary in association with a maternal high-fat diet?"
            ]
        },
        {
            "id": "task847-f6fe5534de9249418dd859ef9d866cdb",
            "input": "Cardiac allograft vasculopathy (CAV) is a major cause of mortality after cardiac transplantation. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is inversely associated with coronary artery disease. In 2 independent studies, we tested the hypothesis that reduced CEC is associated with mortality and disease progression in CAV.', 'We tested the relationship between CEC and survival in a cohort of patients with CAV (n = 35). To determine whether reduced CEC is associated with CAV progression, we utilized samples from the Clinical Trials in Organ Transplantation 05 (CTOT05) study to determine the association between CEC and CAV progression and status at 1 year (n = 81), as assessed by average change in maximal intimal thickness (MIT) on intravascular ultrasound.', 'Multivariable Cox proportional hazard models demonstrated that higher levels of CEC were associated with improved survival (hazard ratio 0.26, 95% confidence interval 0.11 to 0.63) per standard deviation CEC, p = 0.002). Patients who developed CAV had reduced CEC at baseline and 1-year post-transplant. We observed a significant association between pre-transplant CEC and the average change in MIT, particularly among patients who developed CAV at 1 year (\u03b2 = -0.59, p = 0.02, R",
            "output": [
                "Does cholesterol efflux capacity of high-density lipoprotein correlate with survival and allograft vasculopathy in cardiac transplant recipients?"
            ]
        },
        {
            "id": "task847-11b1e241893f4d73b9a6e664a4550fc5",
            "input": "The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide.', 'Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days. The pancreas was disposed, and several sections were stained with hematoxylin-eosin. Immunohistochemistry was used to measure the expressions of glucagon-like peptide 1 receptor (GLP-1R) and cysteinyl aspartate specific proteinase-3 in rat pancreas, and Western blot was used to test the expressions of GLP-1R, light chain 3B-I and -II, and p62 in rat pancreas and AR42J cells. The data were expressed as mean (standard deviation) and analyzed by unpaired Student t test using SPSS 18.0 statistics software (SPSS China, Shanghai, China).', 'Exenatide can induce pathological changes in rat pancreas. The GLP-1R, p62, light chain 3B-II, and cysteinyl aspartate specific proteinase-3 in rat pancreas and AR42J cells treated with exenatide were significantly overexpressed.",
            "output": [
                "Does exenatide induce Impairment of Autophagy Flux to Damage Rat Pancreas?"
            ]
        },
        {
            "id": "task847-96166afefe384977b0d87740d5e0b430",
            "input": "Cape Town, South Africa.', 'To evaluate anti-tuberculosis treatment outcomes and rate of antiretroviral therapy (ART) initiation using weekly community-based adherence support compared to daily directly observed therapy (DOT).', 'This was a retrospective analysis comparing two cohorts treated for tuberculosis (TB) in 70 TB clinics during 6-month periods before and after the introduction of a new adherence model comprising treatment literacy sessions during 2 weeks of DOT, followed by weekly home visits by community care workers to eligible patients managing their own treatment. Odds ratios (ORs) of treatment success and ART initiation were calculated using multivariable random effects logistic regression models. Hazard ratios (HRs) of default and death were calculated using multivariable random effects Cox regression models.', 'The pre-intervention cohort comprised 11\\u2009896 patients with TB and the post-intervention cohort 11\\u2009314. There was no difference in pre- and post-intervention anti-tuberculosis treatment success rates (respectively 82.8% and 82.5%, adjusted OR [aOR] 1.02, 95%CI 0.89-1.17, P = 0.76) nor an increased hazard of death (adjusted HR [aHR] 0.98, 95%CI 0.80-1.21, P = 0.87) or default (aHR 0.97, 95%CI 0.81-1.15, P = 0.69). The ART initiation rate increased from 67% to 74% (aOR 1.43; 95%CI 1.01-1.85, P < 0.01).",
            "output": [
                "Does an integrated community TB-HIV adherence model provide an alternative to DOT for tuberculosis patients in Cape Town?"
            ]
        },
        {
            "id": "task847-80844cc02d0f48408671ba318fdc09c1",
            "input": "Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance.', 'Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS).', 'When genes with an incidence\\u2009>\\u200910% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P\\u2009=\\u2009.0004) and OS (P\\u2009\u2264\\u2009.0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached.",
            "output": [
                "Does next-generation sequencing survey of biliary tract cancer reveal the association between tumor somatic variants and chemotherapy resistance?"
            ]
        },
        {
            "id": "task847-2031812dd5334362923d722d09d7394a",
            "input": "To investigate the effect of antisense non-coding RNA in the INK4 locus (ANRIL) on invasion and metastasis of thyroid cancer (TC).', 'ANRIL expression was significantly up-regulated in TC tissues and cells (P < 0.001), and ANRIL expression was significantly different regarding histological grade and LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation, invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can be reversed by TGF-\u03b21 siRNA. The mRNA levels of p15INK4b, p14ARF and p16INK4a in TPC-1 and SW579 cells increased significantly after silencing ANRIL (all P < 0.001), and TGF-\u03b21 siRNA could reverse the ANRIL siRNA induced increase of p15INK4b; expressions of TGF-\u03b21 and p-Smad2/3 were increased after silencing ANRIL (both P < 0.05).', 'TC and adjacent normal tissues were collected from 105 TC patients. LncRNA ANRIL expressions were detected by qRT-PCR. The siRNA ANRIL and siRNA TGF-\u03b21 were constructed for TPC-1 and SW579 cell line transfection: si-ANRIL group, si-TGF-\u03b21 group, si-ANRIL + si-TGF-\u03b21 group, negative control group and blank group. Effects of ANRIL silencing on proliferation, invasion and metastasis of TC cells was detected by MTT assay, Transwell assay and tail vein injection of nude mice in vitro and in vivo. TGF-\u03b21 and p-Smad2/3 expressions in TGF-\u03b2/Smad signaling pathway were detected by western blot.",
            "output": [
                "Does long non-coding RNA ANRIL promote the invasion and metastasis of thyroid cancer cells through TGF-\u03b2/Smad signaling pathway?"
            ]
        },
        {
            "id": "task847-7f35dc65bf7746d3a07e1807f2342a43",
            "input": "Rhinovirus (RV) infection in asthma induces varying degrees of airway inflammation (e.g. neutrophils), but the underlying mechanisms remain unclear.', 'The major goal was to determine the role of genetic variation [e.g. single nucleotide polymorphisms (SNPs)] of Toll-interacting protein (Tollip) in airway epithelial responses to RV in a type 2 cytokine milieu.', 'DNA from blood of asthmatic and normal subjects was genotyped for Tollip SNP rs5743899 AA, AG and GG genotypes. Human tracheobronchial epithelial (HTBE) cells from donors without lung disease were cultured to determine pro-inflammatory and antiviral responses to IL-13 and RV16. Tollip knockout and wild-type mice were challenged with house dust mite (HDM) and infected with RV1B to determine lung inflammation and antiviral response.', 'Asthmatic subjects carrying the AG or GG genotype (AG/GG) compared with the AA genotype demonstrated greater airflow limitation. HTBE cells with AG/GG expressed less Tollip. Upon IL-13 and RV16 treatment, cells with AG/GG (vs. AA) produced more IL-8 and expressed less antiviral genes, which was coupled with increased NF-\u03baB activity and decreased expression of LC3, a hallmark of the autophagic pathway. Tollip co-localized and interacted with LC3. Inhibition of autophagy decreased antiviral genes in IL-13- and RV16-treated cells. Upon HDM and RV1B, Tollip knockout (vs. wild-type) mice demonstrated higher levels of lung neutrophilic inflammation and viral load, but lower levels of antiviral gene expression.",
            "output": [
                "Does tollip SNP rs5743899 modulate human airway epithelial responses to rhinovirus infection?"
            ]
        },
        {
            "id": "task847-f5f2fcd2b8aa4810851e9f34af20a1ad",
            "input": "To describe the development and application of logic model templates for systematic reviews and health technology assessments (HTAs) of complex interventions.', 'This study demonstrates the development of a method to conceptualize complexity and make underlying assumptions transparent. Examples from systematic reviews with specific relevance to Sub-Saharan Africa (SSA) and other low- and middle-income countries (LMICs) illustrate its usefulness.', 'Two distinct templates are presented: the system-based logic model, describing the system in which the interaction between participants, intervention, and context takes place; and the process-orientated logic model, which displays the processes and causal pathways that lead from the intervention to multiple outcomes.",
            "output": [
                "Do logic models help make sense of complexity in systematic reviews and health technology assessments?"
            ]
        },
        {
            "id": "task847-618c0d342b3147ff97978e07dbcfa395",
            "input": "Limited studies have examined ethnic variation in breastfeeding and complementary feeding practices in developing countries. This study investigated ethnic variation in feeding practices in mothers with children 0-23 months old in Vietnam.', 'We used data on 1875 women who came from the ethnic majority, Kinh (n\\u2009=\\u2009989, randomly sampled from 9875 surveyed Kinh mothers, 10\\xa0% from each province) and three ethnic minorities: E De-Mnong (n\\u2009=\\u2009309), Thai-Muong (n\\u2009=\\u2009229) and Tay-Nung (n\\u2009=\\u2009348). Ethnic minorities were compared with the Kinh group using logistic regression model.', 'Prevalence of breastfeeding initiation within an hour of birth was 69\\xa0% in Thai-Muong, but ~50\\xa0% in other ethnicities. In logistic regression, the prevalence of breastfeeding within one hour was lower in Tay-Nung (OR: 0.54; 95\\xa0% CI: 0.38, 0.77) than the majority Kinh. Prevalence of exclusive breastfeeding under 6\\xa0months was 18, 10, 17, and 33\\xa0% in Kinh, Thai-Muong, Tay-Nung, and E De-Mnong, respectively; compared to the majority Kinh, the prevalence was lower in Thai-Muong (OR: 0.42; 95\\xa0% CI: 0.25, 0.71) and higher in E De-Mnong (OR: 1.99; 95\\xa0% CI: 1.04, 3.82). Overall prevalence of bottle feeding in Thai-Muong and E De-Mnong (~20\\xa0%) was lower than in Kinh (~33\\xa0%): Thai-Muong (OR: 0.50; 95\\xa0% CI: 0.37, 0.68) and E De-Mnong (OR: 0.69; 95\\xa0% CI: 0.50, 0.95). Compared with Kinh (75\\xa0%), fewer ethnic minority children received minimum acceptable diets (33\\xa0% in Thai-Muong, 46\\xa0% in E De-Mnong, and 52\\xa0% in Tay-Nung; P\\u2009<\\u20090.05). Prevalence of minimum acceptable diet (met both dietary frequency and diversity) was lower in Thai-Muong (OR: 0.23; 95\\xa0% CI: 0.11, 0.46), Tay-Nung (OR: 0.52; 95\\xa0% CI: 0.39, 0.69), and E De-Mnong (OR: 0.55; 95\\xa0% CI: 0.33, 0.89) than the majority Kinh.",
            "output": [
                "Do infant and young child feeding practices differ by ethnicity of Vietnamese mothers?"
            ]
        },
        {
            "id": "task847-c45b9ecf1ac34d6595ab90de1637e26a",
            "input": "Teamwork during cardiopulmonary arrest events is important for resuscitation. Teamwork improvement programs are usually lengthy. This study assessed the effectiveness of a 2-hour teamwork training program.', 'A prospective, pretest/posttest, quasi-experimental design assessed the teamwork training program targeted to resident physicians, nurses, and respiratory therapists.', 'Participants took part in a simulated cardiac arrest. After the simulation, participants and trained observers assessed perceptions of teamwork using the Team Emergency Assessment Measure (TEAM) tool (ratings of 0 [low] to 4 [high]). A debriefing and 45 minutes of teamwork education followed. Participants then took part in a second simulated cardiac arrest scenario. Afterward, participants and observers assessed teamwork.', \"Seventy-three team members participated-resident physicians (25%), registered nurses (32%), and respiratory therapists (41%). The physicians had significantly less experience on code teams (P < .001). Baseline teamwork scores were 2.57 to 2.72. Participants' mean (SD) scores on the TEAM tool for the first and second simulations were 3.2 (0.5) and 3.7 (0.4), respectively (P < .001). Observers' mean (SD) TEAM scores for the first and second simulations were 3.0 (0.5) and 3.7 (0.3), respectively (P < .001). Program evaluations by participants were positive.",
            "output": [
                "Does two Hours of Teamwork Training improve Teamwork in Simulated Cardiopulmonary Arrest Events?"
            ]
        },
        {
            "id": "task847-c3b5b4410ad9497fafc06646f2d16cd7",
            "input": "Nocturnal stridor and respiratory abnormalities are important features of multiple system atrophy (MSA) with relevance to patient survival, and they are detected and evaluated mainly through video-polysomnography (video-PSG). Diurnal laryngoscopy seems to yield abnormal findings only in the presence of significant vocal cord (VC) dysfunction.', 'To assess whether specific electrophysiological patterns of diurnal EMG of VC muscles may indicate nocturnal stridor or respiratory dysfunctions in MSA patients.', 'Seventeen patients with probable MSA were examined. A full-night video-PSG to collect standard breathing parameters (apnea/hypopnea index, mean HbSAO', 'Both the laryngeal EMG abnormalities (based on MUAP analysis and kinesiologic EMG investigation of VC muscles) and the laryngoscopic alterations correlated with video-PSG respiratory abnormalities. Specific patterns of EMG findings were consistently found in MSA subjects with nocturnal stridor detected at PSG. In particular, the following EMG findings were related to the severity of breathing abnormalities and the presence of stridor on video-PSG: neurogenic pattern on MUAP analysis of the PCA, paradoxical activation of the TA during inspiration and tonic EMG activity of the TA during quiet breathing.",
            "output": [
                "Are specific patterns of laryngeal electromyography during wakefulness associated to sleep disordered breathing and nocturnal stridor in multiple system atrophy?"
            ]
        },
        {
            "id": "task847-ab2c5ec0885948fcbcbb74a083057513",
            "input": "Postictal generalized EEG suppression (PGES) frequently occurs after generalized convulsive seizures (GCS) and may be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). It is usually determined using conventional scalp EEG which is likely to miss cerebral activity in deeper brain structures. Here, we examined intracranial EEG activity after GCS to unravel the pattern and extent of local brain activity during apparent PGES on scalp EEG (s-PGES).', 'We retrospectively reviewed electroencephalographic data of people with chronic epilepsy who had GCS during presurgical video-EEG monitoring using simultaneous intracranial and scalp EEG (10-20 system) electrodes.', 'Twenty-five GCS (20 with s-PGES) of 15 patients with an average number of 88\u00b142 intracranial electrode contacts were included. The majority of GCS with s-PGES (18 of 20) displayed persisting or reemerging intracranial EEG activity during apparent PGES on scalp EEG. Three patterns were identified: Pattern 1 (11 GCS, 6 patients) consisted of continuous local interictal activity; Pattern 2 (5 GCS, 5 patients) displayed suppressed EEG activity at all intracranial contacts in the early phase of s-PGES, but reemerging local brain activity before s-PGES dissolved; and Pattern 3 (2 GCS, 2 patients) showed persistent local ictal activity during s-PGES. Persisting intracranial EEG activity at PGES onset on scalp EEG was present in 10\u00b114% (range: 0 to 42%) of all intracranial contacts and mostly in the temporal lobe.",
            "output": [
                "Does local brain activity persist during apparently generalized postictal EEG suppression?"
            ]
        },
        {
            "id": "task847-fd0a127fabd64f3dbfb54c91fb32c8b0",
            "input": "Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance.', 'Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests.', 'The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume.",
            "output": [
                "Does interictal epileptic discharge correlate with global and frontal cognitive dysfunction in temporal lobe epilepsy?"
            ]
        },
        {
            "id": "task847-0b16f1b867a747de8ecf6e7c89e606b5",
            "input": "The use of intensity-modulated radiation therapy (IMRT) in rectal cancer has steadily increased over traditional 3D conformal radiotherapy (3D-CRT) due to perceived benefit of delivering higher treatment doses while minimizing exposure to surrounding tissues. However, IMRT is technically challenging and costly, and its effects on rectal cancer outcomes remain unclear.', 'Adults with clinical stage II and III rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy with 45-54\\xa0Gy of radiation and surgery were included from the 2006-2013 National Cancer Data Base. Patients were grouped based the modality of radiation received: IMRT or 3D-CRT. Multivariable regression modeling adjusting for demographic, clinical, and treatment characteristics was used to examine the impact of IMRT vs. 3D-CRT on pathologic downstaging, resection margin positivity, sphincter loss surgery, 30-day unplanned readmission and mortality after surgery, and overall survival.', 'Among 7386 patients included, 3330 (45\\xa0%) received IMRT and 4056 (55\\xa0%) received 3D-CRT. While the mean radiation dose delivered was higher with IMRT (4735 vs. 4608\\xa0cGy, p\\u2009<\\u20090.001), it was associated with higher risks of positive margins (adjusted odds ratio (OR) 1.57; p\\u2009<\\u20090.001) and sphincter loss surgery (OR 1.32; p\\u2009<\\u20090.001). There were no differences between IMRT and 3D-CRT in the likelihood of pathologic downstaging (OR 0.89, p\\u2009=\\u20090.051), unplanned readmission (OR 0.79; p\\u2009=\\u20090.07), or 30-day mortality (OR 0.61; p\\u2009=\\u20090.31) after surgery. Additionally, there were no differences in overall survival at 8\\xa0years (IMRT vs. 3D-CRT: 64 vs. 64\\xa0%; adjusted hazard ratio 1.06, p\\u2009=\\u20090.47).",
            "output": [
                "Is intensity-Modulated Radiation Therapy Associated with Perioperative or Survival Benefit over 3D-Conformal Radiotherapy for Rectal Cancer?"
            ]
        },
        {
            "id": "task847-46dbc512defe4436aaae9ed325656ac8",
            "input": "Chronic HIV/HCV co-infection carries increased risk of cirrhosis, hepatocellular carcinoma, and death. Due to anti-inflammatory properties, HMG co-A inhibitors (statins) may be useful adjunctive therapy to reduce liver disease progression.', 'Clinical information was extracted from the Veterans Affairs HIV and HCV Clinical Case Registries (1999 - 2010). HIV-related variables included combination anti-retroviral therapy (cART) era of diagnosis, CD4 cell count, and percent time with undetectable HIV viral load. Metabolic variables included diabetes, low-HDL, and hypertension. Statin use was measured as percent time with active prescription (time-updated throughout the follow-up period). Cox proportional hazards analysis was used to determine risk factors for cirrhosis (ICD-9 or APRI>2) overall and in groups stratified by alanine aminotransferase (ALT) level above and below 40\\u200aIU/L.', 'The cohort included 5985\\u200aHIV/HCV co-infected veterans. The majority was black race, and the mean age at index date was 45 years. Statin use was significantly protective of cirrhosis for patients with ALT \u226440\\u200aIU/L; for every 30% increase in time on statin, there was a 32% decreased risk of developing cirrhosis (HR 0.68, 95% CI 0.47 -0.98). Diabetes and low-HDL were significantly associated with cirrhosis in patients with ALT > 40\\u200aIU/L (HR 1.15, p\\u200a<\\u200a0.04 and HR 1.3, p\\u200a<\\u200a0.0001).",
            "output": [
                "Do statin drugs decrease progression to cirrhosis in HIV/HCV co-infected individuals?"
            ]
        },
        {
            "id": "task847-feffeb7760144f078a71c26bea197647",
            "input": "Earlier exposure to laparoscopic techniques is thought to be beneficial for medical students. Reports have demonstrated that practice improves performance in laparoscopies. In this study, we intended to evaluate whether medical students' interest in surgery is affected by the amount of practice and the performance on a laparoscopic simulator.\", 'A laparoscopic simulation curriculum was introduced at Taipei Medical University, Wan-Fang Medical Center. Study participants included 36 sixth-year and 14 seventh-year students who were divided according to whether they had indicated an interest (group A) or not (group B) in surgery. The students had twice-a-week practice sessions for 2 weeks. They underwent baseline measurement (BM) before training and posttraining measurement (PTM). Self-guided practice on the simulator was allowed. The learning outcomes were assessed comparing the BM and PTM scores by using the interquartile range (IQR) test. We also tested the correlation between total score and number of self-guided practice sessions.', 'All study participants showed improvement. No differences were observed between BM and PTM scores and between 6th- and 7th-year medical students. Significant differences were found in PTM scores between groups A and B (P < .001). Analysis of variance with a post hoc test for different groups revealed that the PTMs were significantly higher for both the 6th- and 7th-year medical students in group A than for those in group B (P < .001). Total performance scores were improved with a higher number of self-guided practice sessions. Linear regression analysis demonstrated a significant correlation between the number of self-guided practice sessions and total performance score (P < .001).",
            "output": [
                "Does students ' Interest in Surgery affect Laparoscopic Practicing Performance?"
            ]
        },
        {
            "id": "task847-a2444f4a1e7741b0ac0d514f856833f4",
            "input": "Oral squamous cell carcinoma is a prevalent and frequently lethal malignancy worldwide. Existence of treatment-resistant cancer stem cells is considered to be associated with tumor formation, recurrence and metastasis. Wnt/beta-catenin signal is one of the crucial signaling pathways for cancer stem cells. Wnt/beta-catenin signal inhibitor may reduce the population of cancer stem cells and improve therapeutic effects on the cancers.', 'The effects of three derivatives of Wnt/beta-catenin signal inhibitors, HC-1, IC-2 and PN3-13, which we recently developed, on oral squamous cell carcinoma cell line HSC2, were examined by luciferase reporter assay, WST assay, cell sorting assay and apoptosis assay.', 'The reporter assay showed that these small molecule compounds reduced Wnt/beta-catenin transcriptional activity in HSC2 cells. Of these compounds, IC-2 and PN3-13 inhibited cell viability in a dose-dependent manner, whereas HC-1 did not at even higher concentrations. Notably, however, the cell-sorting assay revealed that HC-1 significantly reduces the CD44-positive population of oral squamous cell carcinoma cells, compared to other compounds without affecting cell viability. In addition, HC-1 increases the cytotoxicity of HSC2 cells to 5-fluorouracil. The combination treatment of HC-1 with 5-fluorouracil significantly increased the apoptotic cells whereas treatment by either compound did not.",
            "output": [
                "Does wnt/Beta-Catenin Signal Inhibitor HC-1 sensitize Oral Squamous Cell Carcinoma Cells to 5-Fluorouracil through Reduction of CD44-Positive Population?"
            ]
        },
        {
            "id": "task847-3aeb8ed9d1334ccdb9990ccbb00412ee",
            "input": "Pedunculate oak (Quercus robur L.), an important forest tree in temperate ecosystems, displays an endogenous rhythmic growth pattern, characterized by alternating shoot and root growth flushes paralleled by oscillations in carbon allocation to below- and aboveground tissues. However, these common plant traits so far have largely been neglected as a determining factor for the outcome of plant biotic interactions. This study investigates the response of oak to migratory root-parasitic nematodes in relation to rhythmic growth, and how this plant-nematode interaction is modulated by an ectomycorrhizal symbiont. Oaks roots were inoculated with the nematode Pratylenchus penetrans solely and in combination with the fungus Piloderma croceum, and the systemic impact on oak plants was assessed by RNA transcriptomic profiles in leaves.', 'The response of oaks to the plant-parasitic nematode was strongest during shoot flush, with a 16-fold increase in the number of differentially expressed genes as compared to root flush. Multi-layered defence mechanisms were induced at shoot flush, comprising upregulation of reactive oxygen species formation, hormone signalling (e.g. jasmonic acid synthesis), and proteins involved in the shikimate pathway. In contrast during root flush production of glycerolipids involved in signalling cascades was repressed, suggesting that P. penetrans actively suppressed host defence. With the presence of the mycorrhizal symbiont, the gene expression pattern was vice versa with a distinctly stronger effect of P. penetrans at root flush, including attenuated defence, cell and carbon metabolism, likely a response to the enhanced carbon sink strength in roots induced by the presence of both, nematode and fungus. Meanwhile at shoot flush, when nutrients are retained in aboveground tissue, oak defence reactions, such as altered photosynthesis and sugar pathways, diminished.",
            "output": [
                "Does transcriptome analysis in oak uncover a strong impact of endogenous rhythmic growth on the interaction with plant-parasitic nematodes?"
            ]
        },
        {
            "id": "task847-f89b2200a29740bf9f0b310e9bb983ad",
            "input": "Impaired endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), is an established risk factor for cardiovascular events. FMD is impaired in heart failure (HF) patients, but less is known about hyperemic brachial artery flow. We investigated the relationship between FMD and hyperemic flow with adverse clinical outcomes in HF patients.', 'Brachial artery FMD and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian; mean age (\u00b1 SD) = 56.2 (\u00b112.4) years) with HF and reduced left ventricular ejection fraction (LVEF). Cox proportional hazard models were used to assess the potential explanatory association of FMD and hyperemic flow with the composite outcome of death or cardiovascular hospitalization over a median 5-year follow-up period.', 'Both FMD and hyperemic flow were negatively correlated with age, but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was associated with an increased risk of death or cardiac hospitalization after controlling for traditional risk factors.",
            "output": [
                "Is reactive hyperemia associated with adverse clinical outcomes in heart failure?"
            ]
        },
        {
            "id": "task847-500101ad821a4ddb9c2050edaf624a58",
            "input": "To assess respective roles of serum creatinine (SCr) alone and estimated glomerular filtration rate (eGFR) as an early predictor for contrast-induced nephropathy (CIN) in elderly patients with cancer.', 'eGFR of 348 patients at 65years or older with malignancy who underwent contrast-enhanced computed tomography (CECT) were calculated. eGFR was calculated based on the following three equations: Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI); Modification of Diet in Renal Disease Study (MDRD); Cockcroft-Gault (CG). CIN was subdivided into two groups: CIN', 'After CECT, CIN occurred in 50 (14.4%) patients, including 33 CIN",
            "output": [
                "Is renal assessment using CKD-EPI equation useful as an early predictor of contrast- induced nephropathy in elderly patients with cancer?"
            ]
        },
        {
            "id": "task847-c9e543f7c4324827aec559bf56bbbe74",
            "input": "The aim of this meta-analysis was to study the relation between access site and bivalirudin use on outcomes in patients with acute coronary syndrome (ACS).', 'Bivalirudin and radial access use are 2 strategies that are increasingly used to lower major bleeding in patients with ACS undergoing invasive approaches. The interaction between these 2 strategies and the benefit of using them in combination are unclear.', 'This analysis included randomized controlled trials that compared bivalirudin to heparin with or without glycoprotein IIb/IIIa inhibitors in patients with ACS and reported outcomes stratified by arterial access site. Meta-analyses of outcome data were performed on the basis of access site and anticoagulation regimen. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from event rates using random-effects models.', 'Eight trials with a total of 27,491 patients were included. Bivalirudin reduced major bleeding risk in patients with femoral access (OR: 0.51; 95% CI: 0.46 to 0.6; p\\xa0< 0.001) but not in patients with radial access (OR: 0.75; 95% CI: 0.45 to 1.26; p\\xa0= 0.28). Moreover, radial access reduced major bleeding risk in patients treated with heparin (OR: 0.57; 95% CI: 0.43 to 0.77; p\\xa0< 0.001) but not in patients treated with bivalirudin (OR: 0.96; 95% CI: 0.65 to 1.41; p\\xa0= 0.83). There were no differences in major adverse cardiovascular events or all-cause mortality between bivalirudin and heparin, regardless of access site.",
            "output": [
                "Is combined Use of Bivalirudin and Radial Access in Acute Coronary Syndromes Superior to the Use of Either One Separately : Meta-Analysis of Randomized Controlled Trials?"
            ]
        },
        {
            "id": "task847-cccea7c400314949bbe1cc5abf6ad529",
            "input": "Sepsis is an emergency condition with high mortality and morbidity rate. There are limited data on the association of cancer as a risk factor for mortality in sepsis patients in the emergency department (ED).', 'This retrospective study was conducted at the ED, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. The study period was between January 1st and December 31st, 2014. The inclusion criteria were as follows: adult patients over 15 years of age who presented at the ED with suspicion of sepsis, received treatment at the ED, and whose blood culture was found to be positive. Clinical data were recorded from medical records including the Mortality in Emergency Department Sepsis score (MEDS score). The primary outcome of this study was mortality at one month. Multivariate logistic regression analysis was used to identify independent factors associated with death.', 'During the study period, there were 775 eligible patients. The two most common pathogens identified from blood cultures were Staphylococcus aureus (193 patients; 24.9%) and Escherichia coli (158 patients; 20.4%). At one month after presenting at the ED, 110 patients (14.2%) had died. There were four significant factors for death, having cancer, being on an endotracheal tube, initial diagnosis of bacteremia, and high MED scores. Having cancer had an adjusted OR of 2.12 (95% CI of 1.29, 3.47).",
            "output": [
                "Do cancer Patients Are at High Risk of Mortality if Presenting with Sepsis at an Emergency Department?"
            ]
        },
        {
            "id": "task847-fb0e686ed8294844aac78da4135c9dcc",
            "input": "Cilostazol, a potent type 3 phosphodiesterase inhibitor, is found to reduce neointimal formation by inhibiting vascular smooth muscle cell (VSMC) proliferation. The aim of this study is to investigate whether the inhibitory effect of cilostazol on VSMC proliferation is operated via heme oxygenase-1 (HO-1).', 'In rat carotid arteries, cilostazol up-regulated HO-1 in the neointima of balloon-injured arteries. Treatment of human VSMCs with cilostazol enhanced the expression of HO-1, which was mainly regulated at the transcriptional level. Small interfering RNA knock-down of HO-1 attenuated the inhibitory effect of cilostazol on VSMC proliferation, suggesting the critical role of HO-1 in cilostazol effect. The transcriptional responsiveness of HO-1 to cilostazol was inversely correlated with the length of GT-repeat in human HO-1 promoter. Deletion and mutational analysis of HO-1 promoter along with chromatin immunoprecipitation showed that cyclic AMP response element (CRE)-binding protein (CREB) participated in cilostazol-induced HO-1 transcription. Furthermore, cilostazol triggered a linkage between the CRE and GT-repeat regions in the HO-1 promoter. The promoting effect of cilostazol on HO-1 expression, proliferation inhibition, and chromatin conformation in the HO-1 promoter was greater in VSMCs from subjects with shorter GT-repeat alleles than those with longer alleles.",
            "output": [
                "Does gT-repeat length polymorphism in heme oxygenase-1 promoter determine the effect of cilostazol on vascular smooth muscle cells?"
            ]
        },
        {
            "id": "task847-451aef94aa5e4b4595a07c3b30226875",
            "input": "Fibromyalgia is a syndrome characterized by severe pain, fatigue and sleep disturbance. There is evidence of central hyper-responsiveness to sensory stimulation and impaired cardiovascular autonomic control. Laboratory investigations suggest that mindfulness-based stress reduction (MBSR) may improve autonomic functioning in fibromyalgia. However, these findings may not reflect what occurs during naturalistic conditions, and MBSR studies during real-life functioning are lacking. We conducted a randomized controlled, 3-armed study with 168 female FM patients. This report describes cardiac, respiratory and physical activity findings.', 'Eight-week MBSR was compared to wait-list and to active control intervention. Ambulatory accelerometry and cardiorespiratory function were monitored over 24-h periods at 3 time-points: pre- and post-intervention, and 8-week follow-up. Also baseline levels were compared with an age-matched group of 33 healthy women.', 'Activity, heart rate, respiratory sinus arrhythmia and ventilation were measured. Comparison with controls confirmed differences in cardiac autonomic tone and activity pattern among patients. Most measures also showed effects of time-of-day and point of measurement. There were no effects of treatment. Additionally, there were no relations between patient-reported clinical improvement and objective physiological or accelerometry parameters. Intervention-related benefits in wellbeing were not associated with changes in daytime cardiorespiratory measures or pattern of physical activity.",
            "output": [
                "Does mindfulness-based Intervention Influence Cardiac Autonomic Control or Pattern of Physical Activity in Fibromyalgia During Daily Life : An Ambulatory , Multi-measure Randomized Controlled Trial?"
            ]
        },
        {
            "id": "task847-a6da4b24bb654a76b6004980783fcc64",
            "input": "Knee osteoarthritis (OA) is a degenerative and progressive articular cartilage disease. Infiltration of autologous platelet-rich plasma (PRP) has been proposed as a therapeutic alternative due to the content of biologically active cytokines in PRP. We aimed to compare the clinical response of acetaminophen and intra-articular leukocyte-poor PRP (LP-PRP) in early knee OA.', 'A total of 65 patients with clinically and radiographically documented knee OA (grade 1-2) were analyzed. Patients were randomized into two groups: 32 were treated with acetaminophen (500\\xa0mg/8\\xa0h) over 6\\xa0weeks, and 33 received three intra-articular injections of autologous LP-PRP (once every 2\\xa0weeks). All patients were evaluated by the Visual Analogue Scale (VAS), the Western Ontario and McMaster Universities (WOMAC) score, and the SF-12 health survey at baseline and 6, 12, and 24\\xa0weeks of follow-up. All LP-PRP preparations were analyzed for the platelet, leukocyte, IL-1ra, and TGF-\u03b2 concentrations.', 'The decrease in the VAS pain level in the LP-PRP group was greater than that in the acetaminophen group (p\\xa0<\\xa00.05). Patients treated with LP-PRP showed a sustained improvement in knee function at week 24 (p\\xa0<\\xa00.01). The SF-12 results only indicated an improvement in quality-of-life in the LP-PRP group at 6, 12, and 24\\xa0weeks of follow-up (p\\xa0<\\xa00.01). Both IL-1ra and TGF-\u03b2 were detected in the LP-PRP samples (313.8\\xa0\u00b1\\xa0231.6 and 21,183.8\\xa0\u00b1\\xa08556.3\\xa0pg/mL, respectively).",
            "output": [
                "Is leukocyte-poor platelet-rich plasma more effective than the conventional therapy with acetaminophen for the treatment of early knee osteoarthritis?"
            ]
        },
        {
            "id": "task847-5ef238d1e636437b99d14ca38c983671",
            "input": "The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level.', 'Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort.', 'Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease (p\\xa0<\\xa0.001). Cathepsin G expression was upregulated in histologically unstable plaques (p\\xa0=\\xa0.04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques (p\\xa0=\\xa0.02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques (p\\xa0=\\xa0.03). CCL19 also co-localised with CD3",
            "output": [
                "Is gene and Protein Expression of Chemokine ( C-C-Motif ) Ligand 19 Upregulated in Unstable Carotid Atherosclerotic Plaques?"
            ]
        },
        {
            "id": "task847-abeea04f4fa34de1af65c02eb5579d52",
            "input": "Alternative payment models, such as bundled payments, aim to control rising costs for total knee arthroplasty (TKA) and total hip arthroplasty (THA). Without risk adjustment for patients who may utilize more resources, concerns exist about patient selection and access to care. The purpose of this study was to determine whether lower socioeconomic status (SES) was associated with increased resource utilization following TKA and THA.', \"Using the Michigan Arthroplasty Registry Collaborative Quality Initiative database, we reviewed a consecutive series of 4168 primary TKA and THA patients over a 3-year period. We defined lowest SES based upon the median household income of the patient's ZIP code. Demographics, medical comorbidities, length of stay, discharge destination, and readmission rates were compared between patients of lowest SES and higher SES.\", 'Patients in the lowest SES group had a longer hospital length of stay (2.79 vs 2.22 days, P < .001), were more likely to be discharged to a rehabilitation facility (27% vs 18%, P < .001), and be readmitted to the hospital within 90 days (11% vs 8%, P\\xa0= .002) than the higher SES group. Multivariate analysis revealed that lowest SES was an independent risk factor for all 3 outcome variables (all P < .001).",
            "output": [
                "Do socioeconomic Risk Adjustment Models for Reimbursement Are Necessary in Primary Total Joint Arthroplasty?"
            ]
        },
        {
            "id": "task847-5c91f36f8b244042bc6ead30e3a4f96e",
            "input": "Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however, evidence in humans is lacking.', 'Twelve healthy young men were given oral broad-spectrum antibiotics (ciprofloxacin 500\\u2009mg bid, vancomycin 500\\u2009mg tid and metronidazole 500\\u2009mg tid) for 7 days. At baseline, 1 day, and 6 weeks after antibiotics, blood and feces were sampled. Whole blood and isolated mononuclear cells were stimulated with selected Toll-like receptor agonists and heat-killed bacteria. Microbiota diversity and composition was determined using bacterial 16S rDNA sequencing.', 'One day after the antibiotic course, microbial diversity was significantly lower compared with baseline. After antibiotic therapy, systemic mononuclear cells produced lower levels of tumor necrosis factor (TNF)-\u03b1 after ex vivo stimulation with lipopolysaccharide (LPS). This diminished capacity to produce TNF-\u03b1 was restored 6 weeks after cessation of antibiotic therapy. In whole blood, a reduced capacity to release interleukin (IL)-1\u03b2 and IL-6 was observed after LPS stimulation. Antibiotic treatment did not impact on differential leukocyte counts, phagocytosis, and cell surface markers of neutrophils and monocytes.",
            "output": [
                "Does antibiotic-Induced Gut Microbiota Disruption decrease TNF-\u03b1 Release by Mononuclear Cells in Healthy Adults?"
            ]
        },
        {
            "id": "task847-e643ea4707674c44821eb84014a3c2a0",
            "input": "Tongue squamous cell carcinoma (TSCC) is the most common malignant cancer in the oral cavity, with a high rate of metastasis to the neck lymphoid node. Angiopoietin-like protein 4 (ANGPTL4) and microvessel density (MVD) may be novel indicators for tumor metastasis. The aim of the present study was to investigate the expression and function of ANGPTL4 in TSCC and the relationship between ANGPTL4 and MVD.', 'The expression levels of ANGPTL4 and MVD (CD34) were analyzed in 65 TSCC specimens and the adjacent non-cancerous tissues using immunohistochemistry (IHC). siRNA was delivered into TSCCA cells to downregulate ANGPTL4 expression. Subsequently, validation with real-time RT-PCR and western blot analyses was performed to analyze ANGPTL4 expression levels. In addition, a proliferation assay, migration and invasion assays were carried out.', 'ANGPTL4 expression was associated with tumor stage, lymph node metastasis and MVD expression. Cox regression analysis showed that high levels of ANGPTL4 expression were closely associated with poor survival time. In vitro analyses using qRT-PCR and western blot confirmed that ANGPTL4 was successfully inhibited in TSCCA cells. Suppressing ANGPTL4 resulted in the inhibition of cell proliferation and migration, but neither invasion nor cisplatin resistance was significantly affected.",
            "output": [
                "Does the downregulation of ANGPTL4 inhibit the migration and proliferation of tongue squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-bcb03a5d2232402f9aef4938bda1ed95",
            "input": "Melatonin, the neurohormone for darkness, mediates photoperiod dependent changes in physiology and behavior by targeting specific membrane bound receptors (MT1 and MT2). In the present study, we investigated the impact of MT1 receptor-deficiency on feeding behavior, locomotor activity and mRNA expression levels encoding for the polypeptide Pomc and neuropeptide Y (Npy) in the hypothalamic arcuate nucleus (ARC) and the adenohypophysis (pars distalis, PD and pars intermedia, PI) in a comparison between wild-type (WT) and MT1-deficient (MT1-/-) mice.', 'The MT1-/- mice spent significantly more time in feeding than the WT-mice, while the general locomotor behavior, body weight and the total amount of food consumed did not differ between both genotypes. The nocturnal expression levels of Pomc in ARC and PD were significantly higher in WT as compared to MT1-/- mice and exogenous melatonin administered during the light phase stimulated Pomc expression in WT mice only. No differences were found between WT and MT1-/- mice with regard to Pomc expression levels in the PI.",
            "output": [
                "Does melatonin Receptor 1-Deficiency affect Feeding Dynamics and Pro-Opiomelanocortin Expression in the Arcuate Nucleus and Pituitary of Mice?"
            ]
        },
        {
            "id": "task847-891581d1e4854430877e6c1b2c63c0cc",
            "input": "Dentofacial deformities are dys-morpho-functional disorders involving the temporomandibular joints (TMJ). Many authors have reported a TMJ improvement in dysfunctional subjects with malocclusion after orthodontic or combined orthodontic and surgical treatment particularly for the relief of pain. In particular, few studies have highlighted the demographic and clinical predictors of response to surgical treatment. To date, no genetic factor has yet been identified as a predictor of response to surgical treatment. The aim of this cohort study is therefore to identify single-nucleotide polymorphisms associated with postoperative temporomandibular disorders (TMD) or with TMJ symptoms after orthognathic surgery. Here, we found the AA genotype of SNP rs1643821 (ESR1 gene) as a risk factor for dysfunctional worsening after orthognathic surgery. In addition, we have identified TT genotype of SNP rs858339 (ENPP1 gene) as a protective factor against TMD in a population of patients with dentofacial deformities. Conversely, the heterozygous genotype AT was identified as a risk factor of TMD with respect to the rest of our population. All these elements are particularly important to bring new screening strategies and tailor future treatment.",
            "output": [
                "Do eNPP1 and ESR1 genotypes influence temporomandibular disorders development and surgical treatment response in dentofacial deformities?"
            ]
        },
        {
            "id": "task847-aca8301aeca54b75a8d55cd6bbf7f462",
            "input": "Bone and antler collagen \u03b4(13) C and \u03b4(15) N values are often assumed to be equivalent when measured in palaeodietary, palaeoclimate and palaeocological studies. Although compositionally similar, bone grows slowly and is remodelled whereas antler growth is rapid and remodelling does not occur. These different patterns of growth could result in isotopic difference within antler and between the two tissue types. Here we test whether red deer (Cervus elaphus) bone and antler \u03b4(13) C and \u03b4(15) N values are equivalent, and whether intra-antler isotopic values are uniform.', 'Bone and antler were isotopically analysed from six stags that lived in a temperate maritime climate on the Isle of Rum, Scotland. Multiple antlers from different years were sampled per individual, together with a single bone sample per individual. Up to 12 samples were taken along the length of each antler (total of 25 antlers, 259 samples) so that a chronological record of the isotopic composition during antler growth could be obtained. Collagen was extracted and its \u03b4(13) C and \u03b4(15) N values were measured by continuous-flow isotope ratio mass spectrometry.', 'Intra-antler collagen isotope signatures vary, and show that not all antlers from an individual or a growth year are equivalent in carbon and nitrogen isotopic ratios. \u03b4(15) N values typically increase with distance along antler length, but no overall trend is observed in \u03b4(13) C values. An isotopic offset is visible between bone and antler, with bone \u03b4(13) C and \u03b4(15) N values being higher in most cases.",
            "output": [
                "Are red deer bone and antler collagen isotopically equivalent in carbon and nitrogen?"
            ]
        },
        {
            "id": "task847-a3eec05053294956a83b5fc2d9dcc0c0",
            "input": "Postpartum haemorrhage (PPH) remains the leading cause of maternal morbidity and mortality worldwide. The main strategy for preventing PPH is the use of uterotonic drugs given prophylactically by skilled health workers. However, in settings where many women still deliver at home without skilled attendants, uterotonics are often inaccessible. In such cases, women and their caregivers need to recognize PPH promptly so, as to seek expert care. For this reason, it is important to understand how women and their caregivers recognize PPH, as well as the actions they undertake to prevent and treat PPH in home births. Such knowledge can also inform programs aiming to make uterotonics accessible at the community level.', 'Between April and June 2012, a phenomenological study was carried out in a rural Ugandan district involving 15 in-depth interviews. Respondents were purposively sampled and included six women who had delivered at home in the past year and nine traditional birth attendants (TBAs). The interviews explored how PPH was recognized, its perceived causes, and the practices that respondents used in order to prevent or treat it. Phenomenological descriptive methodology was used to analyse the data.', 'Bleeding after childbirth was considered to be a normal cleansing process, which if stopped or inhibited would lead to negative health consequences to the mother. Respondents used a range of criteria to recognize PPH: rate of blood flow, amount of blood (equivalent to two clenched fists), fainting, feeling thirsty, collapsing or losing consciousness immediately after birth. As a group, respondents seemed to correctly identify women at risk of PPH (those with twin pregnancies, high parity or prolonged labour), but many individuals did not know all the reasons. Respondents used cold drink, uterine massage and traditional medicine to treat PPH.",
            "output": [
                "Is excessive bleeding a normal cleansing process : a qualitative study of postpartum haemorrhage among rural Uganda women?"
            ]
        },
        {
            "id": "task847-6950b3b3577f42ec805ff619f84fa43e",
            "input": "To evaluate the link among thyroid function, glucose/insulin metabolism and steroid hormones in women with polycystic ovary syndrome (PCOS), and to verify if the body mass index (BMI) might influence the interplay between PCOS features and subclinical hypothyroidism (SCH).', 'Case-control study conducted from January to December 2014.', 'One-hundred fifty-four young women with PCOS, according to Rotterdam criteria, and 88 controls were enrolled in an academic research environment. Anthropometric evaluation, hormonal and lipid assays, oral glucose tolerance test (OGTT) and euglycaemic-hyperinsulinaemic clamp were performed. Hirsutism was assessed with the Ferriman-Gallwey (FG) score.', 'SCH was found in 14% of PCOS subjects and in 1% of controls (P\\u2009<\\u20090.01). In PCOS women, TSH levels were directly correlated with fasting glycaemia, but not with other hormonal and metabolic parameters. When PCOS patients were classified on the basis of BMI, TSH levels significantly correlated with insulin secretion, insulin resistance, DHEAS and cortisol levels in obese PCOS women. Inverse correlations were found between TSH and both oestradiol and SHBG in the same group. In nonobese PCOS patients, only waist-to-hip ratio values were correlated with TSH. The prevalence of SCH was not different between nonobese and obese PCOS groups (14 and 15% respectively). However, SCH was associated with higher levels of insulin, DHEAS, cortisol and FG score only in the obese subgroup.",
            "output": [
                "Is the link between metabolic features and TSH levels in polycystic ovary syndrome modulated by the body weight : an euglycaemic-hyperinsulinaemic clamp study?"
            ]
        },
        {
            "id": "task847-5689be4975bf4fe5ad15eabaf6bdd630",
            "input": "PIK3CA is the most frequent somatic mutated oncogene in estrogen receptor (ER) positive breast cancer. We previously observed an association between PIK3CA genotype and aromatase inhibitors (AI) treatment outcome. This study now evaluates whether expression of mRNAs and miRs are linked to PIK3CA genotype and are independently related to AI therapy response in order to define potential expressed biomarkers for treatment outcome.', 'The miR and mRNA expression levels were evaluated for their relationship with the PIK3CA genotype in two breast tumor datasets, i.e. 286 luminal cancers from the TCGA consortium and our set of 84 ER positive primary tumors of metastatic breast cancer patients who received first line AI. BRB Array tools class comparison was performed to define miRs and mRNAs whose expression associate with PIK3CA exon 9 and 20 status. Spearman correlations established miR-mRNA pairs and mRNAs with related expression. Next, a third dataset of 25 breast cancer patients receiving neo-adjuvant letrozole was evaluated, to compare expression levels of identified miRs and mRNAs in biopsies before and after treatment. Finally, to identify potential biomarkers miR and mRNA levels were related with overall survival (OS) and progression free survival (PFS) after first-line AI therapy.', 'Expression of 3 miRs (miR-449a, miR-205-5p, miR-301a-3p) and 9 mRNAs (CCNO, FAM81B, LRG1, NEK10, PLCL1, PGR, SERPINA3, SORBS2, VTCN1) was related to the PIK3CA status in both datasets. All except miR-301a-3p had an increased expression in tumors with PIK3CA mutations. Validation in a publicly available dataset showed that LRG1, PGR, and SERPINA3 levels were decreased after neo-adjuvant AI-treatment. Six miR-mRNA pairs correlated significantly and stepdown analysis of all 12 factors revealed 3 mRNAs (PLCL1, LRG1, FAM81B) related to PFS. Further analyses showed LRG1 and PLCL1 expression to be unrelated with luminal subtype and to associate with OS and with PFS, the latter independent from traditional predictive factors.",
            "output": [
                "Does lRG1 mRNA expression in breast cancer associate with PIK3CA genotype and with aromatase inhibitor therapy outcome?"
            ]
        },
        {
            "id": "task847-0dc1866a9567423fbcfa7f4bf5564360",
            "input": "Splenectomy and pericardial devascularization (SPD) is an effective treatment of upper gastrointestinal bleeding and hypersplenism in cirrhotic patients with portal hypertension. Indocyanine green retention at 15 minutes (ICGR15) was reported to offer better sensitivity and specificity than the Child-Pugh classification in hepatectomy, but few reports describe ICGR15 in SPD. The present study was to evaluate the prognostic value of ICGR15 for cirrhotic patients with portal hypertension who underwent SPD.', 'From January 2012 to January 2015, 43 patients with portal hypertension and hypersplenism caused by liver cirrhosis were admitted in our center and received SPD. The ICGR15, Child-Pugh classification, model for end-stage liver disease (MELD) score, and perioperative characteristics were analyzed retrospectively.', 'Preoperative liver function assessment revealed that 34 patients were Child-Pugh class A with ICGR15 of 13.6%-43.0% and MELD score of 7-20; 8 patients were class B with ICGR15 of 22.8%-40.7% and MELD score of 7-17; 1 patient was class C with ICGR15 of 39.7% and MELD score of 22. The optimal ICGR15 threshold for liver function compensation was 31.2%, which offered a sensitivity of 68.4% and a specificity of 70.8%. Univariate analysis showed preoperative ICGR15, MELD score, surgical procedure, intraoperative blood loss, and autologous blood transfusion were significantly different between postoperative liver function compensated and decompensated groups. Multivariate regression analysis revealed that ICGR15 was an independent risk factor of postoperative liver function recovery (P=0.020).",
            "output": [
                "Is indocyanine green retention a potential prognostic indicator after splenectomy and pericardial devascularization for cirrhotic patients?"
            ]
        },
        {
            "id": "task847-09c6ad8755d545849f7cbd411ddd04b3",
            "input": "Experimental studies in acute pancreatitis (AP) suggest a strong association of acinar cell injury with cathepsin B-dependent intracellular activation of trypsin. However, the molecular events subsequent to trypsin activation and their role, if any, in cell death is not clear. In this study, we have explored intra-acinar events downstream of trypsin activation that lead to acinar cell death.', 'Acinar cells prepared from the pancreas of rats or mice (wild-type, trypsinogen 7, or cathepsin B-deleted) were stimulated with supramaximal cerulein, and the cytosolic activity of cathepsin B and trypsin was evaluated. Permeabilized acini were used to understand the differential role of cytosolic trypsin vs cytosolic cathepsin B in activation of apoptosis. Cell death was evaluated by measuring specific markers for apoptosis and necrosis.', 'Both in\\xa0vitro and in\\xa0vivo studies have suggested that during AP cathepsin B leaks into the cytosol from co-localized organelles, through a mechanism dependent on active trypsin. Cytosolic cathepsin B but not trypsin activates the intrinsic pathway of apoptosis through cleavage of bid and activation of bax. Finally, excessive release of cathepsin B into the cytosol can lead to cell death through necrosis.",
            "output": [
                "Does release of Cathepsin B in Cytosol cause Cell Death in Acute Pancreatitis?"
            ]
        },
        {
            "id": "task847-04e35a8ed8fa45afb17d34e32f4eba15",
            "input": "The aim of this retrospective single-center study was to assess the authors' results in mitral-aortic double valve replacement (DVR), with attention focused on the risk factors of in-hospital mortality (HM). As the initial results showed a strong relationship between HM and aortic prosthesis-patient mismatch (PPM), this led to an assessment of the impact of PPM on the early results of DVR.\", \"Data from 196 consecutive patients (mean age 60 +/- 10 years) who had undergone DVR between January 1996 and December 2011 at the authors' institution were analyzed. A statistical comparison was made of groups defined by the presence/absence of in-hospital death, postoperative complications, and aortic PPM. A logistic regression analysis of the factors associated with HM and their postoperative evolution was also conducted.\", 'Surgery was mostly performed on an elective basis (89.3%), using mainly bileaflet mechanical valves (93.9%). The rate of associated coronary bypass (CABG) was 11.2%. Aortic PPM (i.e., an effective orifice area index (EOAI) < or = 0.85 cm2/m2) was noted in 28.1% of patients. HM (6.63%) was significantly related to PPM (p < 0.002), greater age (p < 0.003), a smaller EOAI (p = 0.005), associated CABG (p < 0.008), and a longer aortic cross-clamp time (p < 0.03). Patients with aortic PPM had a significantly worse early outcome, with higher overall (p < 0.0007) and cardiac (p < 0.05) complication rates, a longer intensive care unit stay (p < 0.03), and an almost six-fold higher rate of HM (16.4% versus 2.8%; p < 0.002). PPM and age as risk factors were included in a predictive model of HM based on logistic regression; a similar model for postoperative complications highlighted PPM, age and cardiopulmonary bypass time as significant risk factors.",
            "output": [
                "Does aortic prosthesis-patient mismatch strongly affect early results of double valve replacement?"
            ]
        },
        {
            "id": "task847-dbb89736a3a7470dbc1c7da2aa1ee637",
            "input": "To determine whether phosphorylated focal adhesion kinase (P-FAK) has prognostic value in colorectal cancer (CRC) and to test whether it has any association with Tensin 4 (TNS4) expression.', 'P-FAK expression was assessed using immunohistochemistry in 462 CRC cases arrayed on a tissue microarray. P-FAK and TNS4 expression were assessed by immunohistochemistry in 40 cases of paired primary colorectal cancer and corresponding hepatic metastases.', 'Nuclear P-FAK expression was observed in 44% of studied cases. Positive nuclear P-FAK expression was associated with shorter disease-specific survival in univariate (p=0.005) and multivariate analysis (p=0.016). P-FAK expression was greater in metastases than the primary tumours (p<0.001) and showed significant association with nuclear TNS4 (p<0.001) in metastases.",
            "output": [
                "Is nuclear expression of phosphorylated focal adhesion kinase associated with poor prognosis in human colorectal cancer?"
            ]
        },
        {
            "id": "task847-4b53bbde740a4ecb8c29dc7d237c15bb",
            "input": "Despite low peri-operative mortality after major lower extremity amputation, long-term mortality remains substantial. Metabolic syndrome is increasing in incidence and prevalence at an alarming rate in the USA.', 'This study was to determine whether metabolic syndrome predicts outcome after major lower extremity amputation.', 'A retrospective review of charts between July 2005 and June 2010.', 'Fifty-four patients underwent a total of 60 major lower extremity amputations. Sixty percent underwent below-knee amputation and 40% underwent above-knee amputation. The 30-day mortality was 7% with no difference in level (below-knee amputation, 8%; above-knee amputation, 4%; P = 0.53). The mean follow-up time was 39.7 months. The 5-year survival was 54% in the whole group, and was independent of level of amputation (P = 0.24) or urgency of the procedure (P = 0.51). Survival was significantly decreased by the presence of underlying chronic kidney disease (P = 0.04) but not by other comorbidities (history of myocardial infarction, P = 0.79; metabolic syndrome, P = 0.64; diabetes mellitus, P = 0.56).",
            "output": [
                "Does chronic kidney disease predict long-term mortality after major lower extremity amputation?"
            ]
        },
        {
            "id": "task847-c434b88f9186400f8378f3833370f0a0",
            "input": "Early recognition and treatment of sepsis improves outcomes. We determined the effects of bedside point-of-care (POC) lactate measurement on test turnaround time, time to administration of IV fluids and antibiotics, mortality, and ICU admissions in adult ED patients with suspected sepsis. We hypothesized that bedside lactate POC testing would reduce time to IV fluids and antibiotics.', 'We compared 80 ED patients with suspected sepsis and a lactate level of 2 mmol/L or greater before and 80 similar patients after introduction of POC lactate measurements. Groups were compared with \u03a7(2) and Mann Whitney U tests. A sample size of 80 patients in each group had 85% power to detect a 30-minute difference in time to IV fluids or antibiotics.', 'Study groups were similar in age, gender, baseline lactate levels, sepsis severity, and Sequential Organ Failure Assessment (SOFA) scores. Introduction of POC lactate was associated with significant reductions in test turnaround time (34 [26-55] vs. 122 [82-149] minutes; P < 0.001), time to IV fluids (55 [34-83] vs. 71 [42-110] minutes; P = 0.03), mortality (6% vs. 19%; P = 0.02), and ICU admissions (33% vs. 51%, P = 0.02), but not time to IV antibiotics (89 [54-156] vs. 88 [60-177] minutes; P = 0.35).",
            "output": [
                "Is eD bedside point-of-care lactate in patients with suspected sepsis associated with reduced time to iv fluids and mortality?"
            ]
        },
        {
            "id": "task847-71907ac43fda40d58c1f5d48a8b926cf",
            "input": "Cancer stemness, observed in several types of glioma stem cells (GSCs), has been demonstrated to be an important barrier for efficient cancer therapy. We have previously reported that cancerous neural stem cells (F3.Ras.CNSCs), derived from immortalized human neural stem cells by a single oncogenic stimulation, form glial tumors in vivo.', 'We searched for a commonly expressed stress modulator in both F3.Ras.CNSCs and GSCs and identified silent mating type information regulation 2, homolog (SIRT1) as a key factor in maintaining cancer stemness.', 'We demonstrate that the expression of SIRT1, expressed in \"cancer cells with neural stemness,\" is critical not only for the maintenance of stem cells, but also for oncogenic transformation. Interestingly, SIRT1 is essential for the survival and tumorigenicity of F3.Ras.CNSCs and GSCs but not for the U87 glioma cell line.",
            "output": [
                "Is sIRT1 required for oncogenic transformation of neural stem cells and for the survival of `` cancer cells with neural stemness '' in a p53-dependent manner?"
            ]
        },
        {
            "id": "task847-8ad8bff4871e4e8d9756571647fa58f6",
            "input": "We aimed to evaluate risk factors for ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii (AbVAP) in critically ill patients.', 'This was a prospective observational study conducted in an intensive care unit (ICU) of a district hospital (6 beds). Consecutive patients were eligible for enrolment if they required mechanical ventilation for >48 hours and hospitalization for >72 hours. Clinical, microbiological, and laboratory parameters were assessed as risk factors for AbVAP by univariate and multivariate analysis.', '193 patients were included in the study. Overall, VAP incidence was 23.8% and AbVAP, 11.4%. Previous hospitalization of another patient with Acinetobacter baumannii infection was the only independent risk factor for AbVAP (OR (95% CI) 12.016 (2.282-19.521) P < 0.001). ICU stay (25 \u00b1 17 versus 12 \u00b1 9\\u2009\\u2009P < 0.001), the incidence of other infections (OR (95% CI) 9.485 (1.640-10.466) P = 0.002) (urinary tract infection, catheter related infection, and bacteremia), or sepsis (OR (95% CI) 10.400 (3.749-10.466) P < 0.001) were significantly increased in patients with AbVAP compared to patients without VAP; no difference was found with respect to ICU mortality.",
            "output": [
                "Is acinetobacter baumannii infection in prior ICU bed occupants an independent risk factor for subsequent cases of ventilator-associated pneumonia?"
            ]
        },
        {
            "id": "task847-b9127b1b6cf44592b6856253cd950c8c",
            "input": "The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer.', 'API5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues.', 'API5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P\\u2009<\\u20090.001), and this increased expression was significantly associated with tumor stage (P\\u2009=\\u20090.004), tumor grade (P\\u2009<\\u20090.001), and chemo-radiation response (P\\u2009=\\u20090.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P\\u2009<\\u20090.001) and high grade CIN (P\\u2009=\\u20090.031). In multivariate analysis, API5+ (P\\u2009=\\u20090.039) and combined API5+/pERK1/2+ (P\\u2009=\\u20090.032) were independent prognostic factors for overall survival.",
            "output": [
                "Is apoptosis inhibitor-5 overexpression associated with tumor progression and poor prognosis in patients with cervical cancer?"
            ]
        },
        {
            "id": "task847-c86be0ba68a0479b95615a7220d474fe",
            "input": "The early recovery period after periacetabular osteotomy (PAO) can be limited by pain and activity restrictions. Modifications of the Bernese PAO, including sparing the rectus tendon and discontinuing routine arthrotomy, may accelerate early postoperative recovery compared with the standard approach.', 'Does a modified approach for PAO (1) lead to improved pain control immediately after surgery; (2) lead to improved ambulation during the hospital stay; (3) lead to shorter stays, less blood loss, and shorter surgical times; and (4) compromise acetabular correction?', \"We retrospectively reviewed all 75 patients who underwent PAO for developmental dysplasia of the hip between August 2009 and May 2013. The control group included 44 consecutive patients who underwent a standard Bernese PAO with rectus takedown (RT). The study group consisted of 31 consecutive patients who underwent PAO using a modified rectus-sparing (RS) approach without routine arthrotomy. The groups were similar in age, body mass index, and American Society of Anesthesiologists score, but the RT group was comprised of a greater percentage of men than the RS group. Outcome variables were collected from patient charts and included inpatient pain, inpatient ambulation as well as length of stay, estimated blood loss, surgical time, and postoperative radiographic measurements. Cohen's f(2) was used to calculate the effect size in the regression analysis and effects were considered small for values<0.15, moderate for 0.15 to 0.34, and large for values>0.35.\", 'Patients who underwent PAO with a RS approach had less overall pain (RT median 4 versus RS median 2); however, the difference may not have been perceptible to the typical patient (p=0.001, f2=0.059). Patients treated with the RS approach ambulated similar distances during the hospital stay with a median 11 feet (interquartile range [IQR], 0-72.5) for the RT group and a median 30 feet (IQR, 0-100) for the RS group (p=0.215, f2=0.095). Patients in the RT group had a median length of stay of 4 days (IQR, 4-5) compared with a median 3 days (IQR, 3-4) in the RS group (p<0.001). The median estimated blood loss was greater (p=0.010) in the RT group (median, 500 mL; IQR, 350-700) versus the RS group (median, 300; IQR, 250-500). The median surgical time was longer (p<0.001) in patients undergoing PAO with the RT approach (median, 159.5 minutes; IQR, 145.5-177) compared with the RS approach (median, 103 minutes; IQR, 75-114). Acetabular reorientation based on postoperative radiographs was not compromised by the modified approach.",
            "output": [
                "Does preservation of the rectus femoris origin during periacetabular osteotomy compromise acetabular reorientation?"
            ]
        },
        {
            "id": "task847-7eeb1484a28a4574a8af8fbdd77bf00c",
            "input": "Solitary hepatocellular carcinoma (HCC) is a good candidate for surgical resection. However, the significance of the size of the tumor in solitary HCC remains unclear.', 'The aim of this study was to evaluate the impact of tumor size on overall and recurrence-free survival of patients with solitary HCC.', 'We retrospectively reviewed 616 patients with histologically confirmed solitary HCC who underwent curative surgical resection between 1994 and 2010. The characteristics and prognosis of patients with HCC were analyzed stratified by tumor size.', 'A total of 403 patients (65 %) had tumors <5 cm, 172 (28 %) had tumors between 5 and 10 cm, and 41 (7 %) had tumors >10 cm. The incidence of microvascular invasion, satellite nodules, and advanced tumor grade significantly increased with tumor size. The 5-year overall and recurrence-free survival rates of HCC <5 cm were 69.6 % and 32 %, respectively, which were significantly better than those of HCC between 5 and 10 cm (58 % and 26 %, respectively) and HCC >10 cm (53 % and 24 %, respectively). On multivariate analysis, cirrhosis (p = 0.0307), Child-Pugh B (p = 0.0159), indocyanine green retention rate at 15 min >10 % (p = 0.0071), microvascular invasion (p < 0.0001), and satellite nodules (p = 0.0009) were independent predictors of poor survival, whereas tumor size >5 cm was not.",
            "output": [
                "Does above 5 cm , size matter anymore in patients with hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-0ea40d13d1964c0abece4b1b5e1d2500",
            "input": "The live oral rotavirus (RV) vaccines have shown a reduced efficacy in Africa. Recent in vitro studies have shown binding of the RV surface protein (VP4) to histo-blood group antigens (HBGAs) in an RV genotype-dependent manner, suggesting them to be putative receptors for RV. The diversity of HBGA phenotypes in different ethnic populations, combined with prevalence/absence of specific RV genotypes, led us to hypothesize whether the genetic variations in HBGAs in a population limit susceptibility to certain RV genotypes, plausibly leading to reduced vaccine efficacy.', 'Association between HBGAs status and susceptibility to RV P genotypes was investigated in children in Burkina Faso and Nicaragua. In total, 242 children with diarrhea in Burkina Faso and Nicaragua were investigated, 93 of whom were RV positive.', 'In Burkina Faso, the P[8] RV strains (n = 27) infected only Lewis- and secretor-positive children (27/27; P < .0001), but no Lewis-negative children. In contrast, the P[6] strains (n = 27) infected predominantly Lewis-negative children (n = 18; P < .0001) but also Lewis-positive children, irrespective of their secretor status. The results from Nicaragua confirmed that all P[8]-infected children (n = 22) were secretor Lewis positive.",
            "output": [
                "Do both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner?"
            ]
        },
        {
            "id": "task847-b1d81a18890b4b32afb88094225cc930",
            "input": "In mice, the farnesoid X receptor is involved in bacterial translocation, which can result in spontaneous bacterial peritonitis in patients with cirrhosis. We investigated if polymorphisms in the farnesoid X receptor gene influence the risk for spontaneous bacterial peritonitis.', 'Laboratory and clinical data of 293 cirrhotic patients with ascites and 226 healthy controls were prospectively collected. The rs56163822, rs11110390 and rs12313471 polymorphisms of the farnesoid X receptor were determined.', '115 (39%) patients had spontaneous bacterial peritonitis. Distribution of all farnesoid X receptor genotypes matched the Hardy-Weinberg equilibrium. Patients with spontaneous bacterial peritonitis had a higher frequency of the rs56163822 GT genotype (7.0%) than patients without (1.7%, OR=4.4, p=0.02). This genotype was confirmed as predictor of spontaneous bacterial peritonitis by binary logistic regression analysis (OR=6.8, p=0.018).",
            "output": [
                "Does a farnesoid X receptor polymorphism predispose to spontaneous bacterial peritonitis?"
            ]
        },
        {
            "id": "task847-137daf67174e45d3ade652ca4fd9e774",
            "input": "Repetitive umbilical cord occlusions (UCOs) in ovine fetus leading to severe acidemia result in adaptive shut-down of electrocortical activity [electrocorticogram (ECoG)] as well as systemic and brain inflammation. We hypothesized that the fetuses with earlier ECoG shut-down as a neuroprotective mechanism in response to repetitive UCOs will show less brain inflammation and, moreover, that chronic hypoxia will impact this relationship.', 'Near-term fetal sheep were chronically instrumented with ECoG leads, vascular catheters, and a cord occluder and then underwent repetitive UCOs for up to 4\\u2009h or until fetal arterial pH was <7.00. Eight animals, hypoxic prior to the UCOs (SaO2 <55%), were allowed to recover 24\\u2009h post insult, while 14 animals, 5 of whom also were chronically hypoxic, were allowed to recover 48\\u2009h post insult, after which brains were perfusion-fixed. Time of ECoG shut-down and corresponding pH were noted, as well as time to then reach pH <7.00 (\u0394T). Microglia (MG) were counted as a measure of inflammation in gray matter layers 4-6 (GM4-6) where most ECoG activity is generated. RESULTS are reported as mean\\u2009\u00b1\\u2009SEM for p\\u2009<\\u20090.05.', \"Repetitive UCOs resulted in worsening acidosis over 3-4\\u2009h with arterial pH decreasing to 6.97\\u2009\u00b1\\u20090.02 all UCO groups' animals, recovering to baseline by 24\\u2009h. ECoG shut-down occurred 52\\u2009\u00b1\\u20097\\u2009min before reaching pH <7.00 at pH 7.23\\u2009\u00b1\\u20090.02 across the animal groups. MG counts were inversely correlated to \u0394T in 24\\u2009h recovery animals (R\\u2009=\\u2009-0.84), as expected. This was not the case in normoxic 48\\u2009h recovery animals, and, surprisingly, in hypoxic 48\\u2009h recovery animals, this relationship was reversed (R\\u2009=\\u20090.90).",
            "output": [
                "Does adaptive brain shut-down counteract neuroinflammation in the near-term ovine fetus?"
            ]
        },
        {
            "id": "task847-1b7e6acc7262472ea33bd90edd635723",
            "input": "Biotechnological screening processes are performed since more than 8 decades in small scale shaken bioreactors like shake flasks or microtiter plates. One of the major issues of such reactors is the sufficient oxygen supply of suspended microorganisms. Oxygen transfer into the bulk liquid can in general be increased by introducing suitable baffles at the reactor wall. However, a comprehensive and systematic characterization of baffled shaken bioreactors has never been carried out so far. Baffles often differ in number, size and shape. The exact geometry of baffles in glass lab ware like shake flasks is very difficult to reproduce from piece to piece due to the hard to control flow behavior of molten glass during manufacturing. Thus, reproducibility of the maximum oxygen transfer capacity in such baffled shake flasks is hardly given.', 'As a first step to systematically elucidate the general effect of different baffle geometries on shaken bioreactor performance, the maximum oxygen transfer capacity (OTRmax) in baffled 48-well microtiter plates as shaken model reactor was characterized. This type of bioreactor made of plastic material was chosen, as the exact geometry of the baffles can be fabricated by highly reproducible laser cutting. As a result, thirty different geometries were investigated regarding their maximum oxygen transfer capacity (OTRmax) and liquid distribution during shaking. The relative perimeter of the cross-section area as new fundamental geometric key parameter is introduced. An empirical correlation for the OTRmax as function of the relative perimeter, shaking frequency and filling volume is derived. For the first time, this correlation allows a systematic description of the maximum oxygen transfer capacity in baffled microtiter plates.",
            "output": [
                "Is cross-section perimeter a suitable parameter to describe the effects of different baffle geometries in shaken microtiter plates?"
            ]
        },
        {
            "id": "task847-9aaee9711c404a91820dc0b7f19c40be",
            "input": "Health-risk behaviours (HRB) increase the risk of disability and chronic diseases at an older age. This study aimed to compare Slovakia and the Netherlands regarding differences in the prevalence of HRB by neighbourhood and individual deprivation and to determine whether area differences could be explained by the socio-economic position (SEP) of the residents.', 'We obtained data on non-institutionalized residents aged \u2265 65 years from the EU-FP7: EURO-URHIS 2 project from Slovak (N = 665, response rate 44.0%) and Dutch cities (N = 795, response rate 50.2%). HRB concerned daily smoking, binge drinking, physical activity, consumption of fruits and vegetables and body mass index. Area deprivation was measured by the neighbourhood unemployment rate. Individual SEP was measured by education and household income with financial strain. We used multilevel logistic regression.', 'In Slovakia, no HRB was associated with either neighbourhood unemployment or individual SEP. The elderly in the Netherlands from the least favourable neighbourhoods were more likely to be daily smokers [odds ratio (OR) 2.32; 95% confidence interval (CI) 1.25, 4.30] and overweight (OR 1.84; 95% CI 1.24, 2.75) than residents from the most favourable ones. For the Dutch elderly the gradients varied per HRB and per individual-level SEP indicator. Individual SEP explained country differences in the association of area unemployment with smoking and lack of physical activity but not that with overweight.",
            "output": [
                "Does the effect of neighbourhood unemployment on health-risk behaviours in elderly differ between Slovak and Dutch cities?"
            ]
        },
        {
            "id": "task847-81fc7573b13b4c2fb308bba45b01ed4e",
            "input": "Ellagic acid (EA), a major polyphenolic compound of pomegranate juice, produces antinociceptive effects, which are mediated through opioidergic and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathways. The present study was conducted to elucidate the peripheral antinociceptive effect of EA alone and in combination with sildenafil in the rat formalin test.', 'Pain was produced by intraplantar injection of formalin (2.5%) in rats and nociceptive behavior was measured as the number of flinches every 5 min in 60 min after injection.', 'Local administration of EA and sildenafil dose-dependently increased the nociception threshold in both phases of the test. Moreover, sub-effective doses of sildenafil (25 or 50 mcg/paw, i.p.) significantly and dose-dependently enhanced the antinociception induced by a sub-effective dose of EA (60 mcg/paw, i.pl.) in both phases of the test. The antinociception produced by these drugs alone, or in combination, was due to a peripheral site of action, since the administration in the contralateral paw was ineffective.",
            "output": [
                "Does sildenafil enhance the peripheral antinociceptive effect of ellagic acid in the rat formalin test?"
            ]
        },
        {
            "id": "task847-4ecc9865b0034487a7463cd93a7754a5",
            "input": "Application of vitamin K to the skin has been used for suppression of pigmentation and resolution of bruising. However, in rats, no study was reported on its effect regarding wound healing. Thus, the present study was designed to examine the healing effects of creams prepared from vitamin K1 on full-thickness wound in rats.', 'For inducing full-thickness wound in rats, the excisional wound model was used. Five groups consisting of 8 rats each were used. Vitamin K cream (1% and 2%, w/w) was prepared in eucerin base and applied on the wound once a day until complete healing had occurred. Healing was defined by decreased wound margin (wound contraction), re-epithelialization, tensile strength and hydroxyproline content. Histopathological examination was also done.', 'The effects produced by the topical vitamin K showed significant (P < 0.01) healing when compared with control group in parameters such as wound contraction, epithelialization period, hydroxyproline content and tensile strength. Histopathological studies also showed improvement with vitamin K.",
            "output": [
                "Does topical vitamin K1 promote repair of full thickness wound in rat?"
            ]
        },
        {
            "id": "task847-96213530457a4dbc812d67cb25e53250",
            "input": "Fatty Acid Binding Protein-4 (FABP4) is a member of a family of FABP proteins that regulate intracellular lipid trafficking in diverse tissues. We recently showed that FABP4 regulates triglyceride accumulation in primary human trophoblasts. To assess the function of placental FABP4 in\\xa0vivo, we tested the hypothesis that FABP4 is expressed in the murine placenta, and regulates placenta triglyceride accumulation.', 'C57Bl/6 wild type or Fabp4-null mice were time-bred, and fetuses and placentas harvested at different time points during pregnancy. Placental FABP4 expression was assessed at different gestational ages, using quantitative PCR, immunohistochemistry, immunofluorescence and western immunoblotting. FABPs expression was examined by RT-qPCR. Placental lipids were extracted using the Folch method and triglyceride levels determined using a colorimetric quantification kit.', 'Using immunohistochemistry, we found that FABP4 was expressed in the placental labyrinthine layer, predominantly in endothelial cells in association with CD31 positive fetal capillaries. The level of placental FABP4 mRNA and protein increased from E12.5 to E16.5 and slightly decreased at E18.5. Breeding of Fabp4 heterozygous mice resulted in embryonic genotypes that followed a Mendelian distribution and exhibited normal weight and morphology, triglyceride content, and expression of other FABP family members. Exposure to hypoxia (O2\\xa0=\\xa012%) between E12.5-E18.5 did not uncover a difference between wild type and Fabp4-null mice.",
            "output": [
                "Is fatty acid binding protein-4 expressed in the mouse placental labyrinth , yet is dispensable for placental triglyceride accumulation and fetal growth?"
            ]
        },
        {
            "id": "task847-1b76d00e2c1d4c59a4db93ec5095d41f",
            "input": "In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice.', 'We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level.', 'U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction.",
            "output": [
                "Is low birth weight associated with adiposity , impaired skeletal muscle energetics and weight loss resistance in mice?"
            ]
        },
        {
            "id": "task847-bfc6a0cf12a6405794d8cab383c1386d",
            "input": "Recent studies found that early repolarization (ER) is significantly more common in survivors of aborted sudden cardiac death. We hypothesized that ER might be more common in patients with ST elevation myocardial infarction (STEMI) who have complications of atrial and ventricular arrhythmias.', 'This study included 266 patients with acute STEMI undergoing primary percutaneous coronary intervention. Twelve-lead electrocardiograms were analyzed for ER, defined as J-point elevation \u2265 0.1 mV and \"notching\" and \"slurring\" of the terminal part of the QRS complex in at least 2 lateral or inferior leads. Acute and late atrial and ventricular arrhythmic events were evaluated.', 'The ER pattern was observed in 76 patients (28.6%). Atrial arrhythmia [21/76 (27.6%) vs. 22/190 (11.6%), p=0.001] and ventricular arrhythmia [16/76 (21.1%) vs. 16/190 (8.4%), p=0.004] were more frequently complicated in patients with ER than those without during hospitalization. ER was a significant independent predictor of developing atrial (HR=2.682, 95% CI=1.355-5.310, p=0.005) and ventricular arrhythmia (HR=2.936, 95% CI=1.360-6.335, p=0.006). Three patients with ER and ventricular fibrillation expired during hospitalization [3.9% (3/76) vs. 0% (0/190), p=0.023]. However, the presence of ER did not affect the late recurrence of atrial and ventricular arrhythmia.",
            "output": [
                "Is early repolarization associated with atrial and ventricular tachyarrhythmias in patients with acute ST elevation myocardial infarction undergoing primary percutaneous coronary intervention?"
            ]
        },
        {
            "id": "task847-383b50ca1c944aceba12819489d723f7",
            "input": "Insulin (INS) resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome, and obesity. The mechanism by which INS and estrogen interact is unknown. We hypothesize that estrogen binds directly to INS and the insulin receptor (IR) producing INS resistance.', 'To determine the binding constants of steroid hormones to INS, the IR, and INS-like peptides derived from the IR; and to investigate the effect of estrogens on the binding of INS to its receptor.', 'Ultraviolet spectroscopy, capillary electrophoresis, and NMR demonstrated estrogen binding to INS and its receptor. Horse-radish peroxidase-linked INS was used in an ELISA-like procedure to measure the effect of estradiol on binding of INS to its receptor.', 'Binding constants for estrogens to INS and the IR were determined by concentration-dependent spectral shifts. The effect of estradiol on INS binding to its receptor was determined by shifts in the INS binding curve.', 'Estradiol bound to INS with a K d of 12\\u2009\u00d7\\u200910(-9)\\u2009M and to the IR with a K d of 24\\u2009\u00d7\\u200910(-9)\\u2009M, while other hormones had significantly less affinity. Twenty-two nanomolars of estradiol shifted the binding curve of INS to its receptor 0.8 log units to the right.",
            "output": [
                "Does estradiol bound to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro?"
            ]
        },
        {
            "id": "task847-2863e8a76f80426f84a5305f44c2f64d",
            "input": "Biomarkers predictive of recovery from acute kidney injury (AKI) after liver transplantation (LT) could enhance decision algorithms regarding the need for liver-kidney transplantation or renal sparing regimens. Multianalyte plasma/urine kidney injury protein panels were performed immediately before and 1 month post-LT in an initial test group divided by reversible pre-LT AKI (rAKI = post-LT renal recovery) versus no AKI (nAKI). This was followed by a larger validation set that included an additional group: irreversible pre-LT AKI (iAKI = no post-LT renal recovery). In the test group (n = 16), six pre-LT plasma (not urine) kidney injury proteins (osteopontin [OPN], neutrophil gelatinase-associated lipocalin, cystatin C, trefoil factor 3, tissue inhibitor of metalloproteinase [TIMP]-1, and \u03b2-2-microglobulin) were higher in rAKI versus nAKI (P < 0.05) and returned to normal values with renal recovery post-LT. In the validation set (n = 46), a number of proteins were significantly higher in both rAKI and iAKI versus nAKI. However, only pre-LT plasma OPN (P = 0.009) and TIMP-1 (P = 0.019) levels were significantly higher in rAKI versus iAKI. Logistic regression modeling was used to correlate the probability of post-LT rAKI, factoring in both pre-LT protein markers and clinical variables. A combined model including elevated OPN and TIMP-1 levels, age <57, and absence of diabetes had the highest area under the curve of 0.82, compared to protein-only and clinical variable-only models.",
            "output": [
                "Do plasma protein biomarkers enhance the clinical prediction of kidney injury recovery in patients undergoing liver transplantation?"
            ]
        },
        {
            "id": "task847-0edf581dbf4d4b65ac36a5d57d800894",
            "input": "Higher levels of physical activity have been associated with improved survival after breast cancer diagnosis. However, no previous studies have considered the influence of the social and built environment on physical activity and survival among breast cancer patients.', \"Our study included 4,345 women diagnosed with breast cancer (1995-2008) from two population-based studies conducted in the San Francisco Bay Area. We examined questionnaire-based moderate/strenuous recreational physical activity during the 3 years before diagnosis. Neighborhood characteristics were based on data from the 2000 US Census, business listings, parks, farmers' markets, and Department of Transportation. Survival was evaluated using multivariable Cox proportional hazards models, with follow-up through 2009.\", 'Women residing in neighborhoods with no fast-food restaurants (vs. fewer fast-food restaurants) to other restaurants, high traffic density, and a high percentage of foreign-born residents were less likely to meet physical activity recommendations set by the American Cancer Society. Women who were not recreationally physically active had a 22% higher risk of death from any cause than women that were the most active. Poorer overall survival was associated with lower neighborhood socioeconomic status (SES) (p(trend) = 0.02), whereas better breast cancer-specific survival was associated with a lack of parks, especially among women in high-SES neighborhoods.",
            "output": [
                "Does neighborhood influence on recreational physical activity and survival after breast cancer?"
            ]
        },
        {
            "id": "task847-86bbd60a4796479b9e73aa01c2a43722",
            "input": "The mechanisms responsible for the cardiac dysfunction associated with dietary protein restriction (PR) are poorly understood. Thus, this study was designed to evaluate the effects of PR on calcium kinetics, basal and \u03b2-adrenergic contractility in murine ventricular cardiomyocytes.', 'After breastfeeding male Fisher rats were distributed into a control group (CG, n = 20) and a protein-restricted group (PRG, n = 20), receiving isocaloric diets for 35 days containing 15% and 6% protein, respectively. Biometric and hemodynamic variables were measured. After euthanasia left ventricles (LV) were collected for histopathological evaluation, SERCA2a expression, cardiomyocytes contractility and Ca(2+)sparks analysis.', 'PRG animals showed reduced general growth, increased heart rate and arterial pressure. These animals presented extracellular matrix expansion and disorganization, cardiomyocytes hypotrophy, reduced amplitudes of shortening and maximum velocity of contraction and relaxation at baseline and after \u03b2-adrenergic stimulation. Reduced SERCA2a expression as well as higher frequency and lower amplitude of Ca(2+)sparks were observed in PRG cardiomyocytes.",
            "output": [
                "Is basal and \u03b2-adrenergic cardiomyocytes contractility dysfunction induced by dietary protein restriction associated with downregulation of SERCA2a expression and disturbance of endoplasmic reticulum Ca2+ regulation in rats?"
            ]
        },
        {
            "id": "task847-4feb07d80b3f494bbfd0a9a654d0020d",
            "input": "Despite new therapeutic approaches, metastatic melanomas still have a poor prognosis. Statins reduce low-density lipoprotein cholesterol and exert anti-inflammatory and anti-proliferative actions. We have recently shown that simvastatin triggers an apoptotic burst in human metastatic melanoma cells by the synthesis of an autocrine factor.', 'The current in vitro study was performed in human metastatic melanoma cell lines (A375, 518a2) and primary human melanocytes and melanoma cells. The secretome of simvastatin-stressed cells was analysed with two-dimensional difference gel electrophoresis and MS. The signalling pathways involved were analysed at the protein and mRNA level using pharmacological approaches and siRNA technology.', 'Simvastatin was shown to activate a stress cascade, leading to the synthesis of 15-deoxy-12,14-PGJ2 (15d-PGJ2 ), in a p38- and COX-2-dependent manner. Significant concentrations of 15d-PGJ2 were reached in the medium of melanoma cells, which were sufficient to activate caspase 8 and the mitochondrial pathway of apoptosis. Inhibition of lipocalin-type PGD synthase, a key enzyme for 15d-PGJ2 synthesis, abolished the apoptotic effect of simvastatin. Moreover, 15d-PGJ2 was shown to bind to the fatty acid-binding protein 5 (FABP5), which was up-regulated and predominantly detected in the secretome of simvastatin-stressed cells. Knockdown of FABP5 abolished simvastatin-induced activation of PPAR-\u03b3 and amplified the apoptotic response.",
            "output": [
                "Does autocrine secretion of 15d-PGJ2 mediate simvastatin-induced apoptotic burst in human metastatic melanoma cells?"
            ]
        },
        {
            "id": "task847-10f6f5d2f91d428287afdb12fb6799b2",
            "input": "Wiskott-Aldrich syndrome (WAS) is a severe disorder characterized by thrombocytopenia, eczema, immunodeficiency, and increased risk of autoimmune disease and lymphoid malignancies. The immunodeficiency caused by a lack of WAS protein expression has been mainly attributed to defective T-cell functions. Whether WAS mutations differentially influence the T-cell receptor (TCR) diversity of different T-cell subsets is unknown.', 'We aimed to identify the degree and pattern of skewing in the variable region of the TCR \u03b2-chain (V\u03b2) in different T-cell subsets from patients with WAS.', 'The TCR repertoire diversity in total peripheral T\\xa0cells, sorted CD4(+) and CD8(+) T cells, and CD45RA(+) (CD45RA(+)CD45RO(-) cells) and CD45RO(+) (CD45RA(-)CD45RO(+) cells) CD4(+) and CD8(+) T cells from patients with WAS and age-matched healthy control subjects was analyzed and compared by using spectratyping of complementarity-determining region 3. The complementarity-determining region 3 of TCR\u03b2 transcripts in CD45RA(+)CD4(+) and CD45RA(+)CD8(+) T cells, CD45RO(+)CD4(+) T cells, CD8(+) terminally differentiated effector memory T (Temra) cells, and naive CD8(+) T cells (CD8(+)CD45RO(-)CCR7(+) cells) from patients and control subjects were analyzed and compared by using high-throughput sequencing.', 'The TCR repertoire diversity in CD45RO(+)CD4(+) T cells and CD8(+) Temra cells of patients with WAS was significantly skewed in comparison with that seen in age-matched control subjects.",
            "output": [
                "Is t-cell receptor diversity selectively skewed in T-cell populations of patients with Wiskott-Aldrich syndrome?"
            ]
        },
        {
            "id": "task847-bc6651c5ae3c40feb4c92935393da52f",
            "input": "Greater body mass index (BMI) has been associated with less radiographic progression in rheumatoid arthritis (RA). We evaluated the association between BMI and joint damage progression as measured by X-ray and MRI.', '1068 subjects with RA from two clinical trials of golimumab (GO-BEFORE and GO-FORWARD) had radiographs performed at weeks 0, 52 and 104 and evaluated using the van der Heijde-Sharp (vdHS) scoring system. Contrast-enhanced MRIs of the dominant wrist and hand were obtained at weeks 0, 12, 24, 52 and 104. Multivariable logistic regression evaluated the risk of radiographic progression for each BMI category (<25, 25-30, >30\\u2005kg/m(2)). Within GO-BEFORE, piecewise, robust generalised estimating equations marginal models assessed the probability of MRI erosion progression for each BMI category. Multivariable linear regression models assessed baseline associations between BMI and bone oedema (a precursor of bone erosion).', 'Higher BMI category was associated with a lower probability of progression in vdHS score at weeks 52 and 104 independent of potential confounders. Higher BMI was also independently associated with a lower probability of progression in MRI erosion score over 2 years. Subjects with greater BMI demonstrated less bone oedema independent of differences in other disease severity measures, including MRI synovitis in the same joints.",
            "output": [
                "Does greater body mass independently predict less radiographic progression on X-ray and MRI over 1-2 years?"
            ]
        },
        {
            "id": "task847-6061d1c5baea4b70858a153b110a9d93",
            "input": "Although numerous investigations have compared gene expression microarray platforms, preprocessing methods and batch correction algorithms using constructed spike-in or dilution datasets, there remains a paucity of studies examining the properties of microarray data using diverse biological samples. Most microarray experiments seek to identify subtle differences between samples with variable background noise, a scenario poorly represented by constructed datasets. Thus, microarray users lack important information regarding the complexities introduced in real-world experimental settings. The recent development of a multiplexed, digital technology for nucleic acid measurement enables counting of individual RNA molecules without amplification and, for the first time, permits such a study.', 'Using a set of human leukocyte subset RNA samples, we compared previously acquired microarray expression values with RNA molecule counts determined by the nCounter Analysis System (NanoString Technologies) in selected genes. We found that gene measurements across samples correlated well between the two platforms, particularly for high-variance genes, while genes deemed unexpressed by the nCounter generally had both low expression and low variance on the microarray. Confirming previous findings from spike-in and dilution datasets, this \"gold-standard\" comparison demonstrated signal compression that varied dramatically by expression level and, to a lesser extent, by dataset. Most importantly, examination of three different cell types revealed that noise levels differed across tissues.",
            "output": [
                "Does comparison of gene expression microarray data with count-based RNA measurements inform microarray interpretation?"
            ]
        },
        {
            "id": "task847-c7bcb1fc72b243b8ad1d1471e97ec588",
            "input": "Earlier work described a mutation in DEC2 also known as BHLHE41 (basic helix-loophelix family member e41) as causal in a family of short sleepers, who needed just 6 h sleep per night. We evaluated whether there were other variants of this gene in two well-phenotyped cohorts.', 'Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase.', 'We identified new variants of the BHLHE41 gene in two cohorts who had either acute sleep deprivation (n = 200) or chronic partial sleep deprivation (n = 217). One variant, Y362H, at another location in the same exon occurred in one twin in a dizygotic twin pair and was associated with reduced sleep duration, less recovery sleep following sleep deprivation, and fewer performance lapses during sleep deprivation than the homozygous twin. Both twins had almost identical amounts of non rapid eye movement (NREM) sleep. This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro. Another variant in the same exome had no effect on sleep or response to sleep deprivation and no effect on CLOCK/BMAL1 transactivation. Random mutagenesis identified a number of other variants of BHLHE41 that affect its function.",
            "output": [
                "Is a novel BHLHE41 variant associated with short sleep and resistance to sleep deprivation in humans?"
            ]
        },
        {
            "id": "task847-5b1e01130f83464b8694a07c073225a8",
            "input": "The involvement of subcortical deep gray matter and cortical thinning associated with mild Parkinson disease remains poorly understood. We assessed cortical thickness and subcortical volumes in patients with Parkinson disease without dementia and evaluated their associations with cognitive dysfunction.', 'The study included 90 patients with mild Parkinson disease without dementia. Neuropsychological assessments classified the sample into patients with mild cognitive impairment (n = 25) and patients without cognitive impairment (n = 65). Volumetric data for subcortical structures were obtained by using the FMRIB Integrated Registration and Segmentation Tool while whole-brain, gray and white matter volumes were estimated by using Structural Image Evaluation, with Normalization of Atrophy. Vertex-based shape analyses were performed to investigate shape differences in subcortical structures. Vertex-wise group differences in cortical thickness were also assessed. Volumetric comparisons between Parkinson disease with mild cognitive impairment and Parkinson disease with no cognitive impairment were performed by using ANCOVA. Associations of subcortical structures with both cognitive function and disease severity were assessed by using linear regression models.', 'Compared with Parkinson disease with no cognitive impairment, Parkinson disease with mild cognitive impairment demonstrated reduced volumes of the thalamus (P = .03) and the nucleus accumbens (P = .04). Significant associations were found for the nucleus accumbens and putamen with performances on the attention/working memory domains (P < .05) and nucleus accumbens and language domains (P = .04). The 2 groups did not differ in measures of subcortical shape or in cortical thickness.",
            "output": [
                "Is subcortical atrophy associated with cognitive impairment in mild Parkinson disease : a combined investigation of volumetric changes , cortical thickness , and vertex-based shape analysis?"
            ]
        },
        {
            "id": "task847-814c7d19f284459ca11e7bcf663943f6",
            "input": "Hepatocellular carcinoma (HCC) is one of the most common solid tumors and ranks the third leading cause of cancer mortality worldwide. The purpose of this study was to examine the expression dynamics of GOLPH3 in HCC tissue samples, and explore the correlation between GOLPH3 expression and prognosis in patients with HCC.', 'The levels of Golgi phosphoprotein 3 (GOLPH3) mRNA and protein in liver cancer cell lines and fresh tissues were determined by qRT-PCR and Western blotting. Additionally, the protein expression of GOLPH3 was detected by immunohistochemistry.', 'High GOLPH3 expression was positively correlated with serum AFP level (P=0.015) and tumor recurrence or metastasis (P=0.010). In addition, liver cancer patients with high GOLPH3 expression had significantly poorer overall survival (HR, 1.87; 95% CI, 1.19-2.94; P=0.006) and poorer disease-free survival (HR, 1.90; 95% CI, 1.21-2.98; P=0.005) than those with low GOLPH3 expression. The cumulative 5-year survival rate was only 35.19% (95% CI, 26.18%-44.20%) in the high GOLPH3 expression group, whereas it was 55.93% (95% CI, 43.26%-68.60%) in the low GOLPH3 expression group. Furthermore, multivariate Cox regression analysis demonstrated that the expression of GOLPH3, tumor size and tumor multiplicity were independent prognostic predictors for HCC patients.",
            "output": [
                "Is gOLP3 a predictor of survival in patients with hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-6fc9e870cd0b4e1bb9d413e19b96a891",
            "input": "Follicular variant of papillary thyroid cancer (FVPTC) is the most common and fastest growing subtype of papillary thyroid cancer (PTC) with features of both PTC and follicular thyroid cancer (FTC). The purpose of this study was to determine the patient and tumor features associated with lymph node metastases (LNM) in FVPTC.', 'This was a retrospective review of adult (\u226518) patients with histologically confirmed diagnoses of FVPTC within the SEER database between 1988 and 2009. LNM were defined by at least two lymph nodes with metastatic disease. To determine factors associated with LNM, we constructed a multivariate logistic regression model from significant variables (p < 0.05) identified on univariate analysis. Similarly, we used a Cox proportional hazards model to understand the relative importance of LNM in determining disease-specific mortality (DSM).', 'Of the 20,357 cases of FVPTC with lymph node data available, 1,761 (8.7%) had LNM; 61.1% of these LNM were located in the central neck and 38.9% were in the lateral neck. Extrathyroidal extension (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.2-3.0, p < 0.01) and multifocality (OR 3.0, 95% CI 2.5-3.6, p < 0.01) were the strongest predictors of LNM. Importantly, LNM did not independently predict DSM (p = 0.52). Tumor size >4 cm (hazards ratio [HR] 5.3, 95% CI 2.2-12.8, p < 0.01) and extrathyroidal extension (HR 8.2, 95% CI 3.0-22.0, p < 0.01) were the strongest predictors of DSM.",
            "output": [
                "Do lymph node metastases impact survival in follicular variant papillary thyroid cancer?"
            ]
        },
        {
            "id": "task847-cc566dc2d0a24a86b3f68a845b439ea2",
            "input": "Extracellular histones exert part of their prothrombotic activity through the stimulation of blood cells. Besides platelets, histones can bind to red blood cells (RBCs), which are important contributors to thrombogenesis, but little is known about the functional consequences of this interaction.', 'To evaluate the effect of histones on the procoagulant potential of human RBCs with particular regard to the expression of surface phosphatidylserine (PS).', 'PS exposure on human RBCs treated with a natural mixture of histones or recombinant individual histones was evaluated with fluorescein isothiocyanate-annexin-V binding and measured with flow cytometry. Calcium influx in RBCs loaded with the calcium-sensitive fluorophore Fluo-4\\xa0AM was assessed with flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated with a purified prothrombinase assay and a one-stage plasma recalcification clotting test.', 'Natural histones induced PS exposure on RBCs in a dose-dependent manner, and neutralization or cleavage of histones by heparin or activated protein\\xa0C, respectively, abolished PS externalization. H4 was mainly responsible for the stimulating activity of histones, whereas the other subtypes were almost ineffective. Similarly, natural histones and H4 induced influx of calcium into RBCs, whereas the other individual histones did not. Histone-induced exposure of PS on RBCs translated into increased prothrombinase complex-mediated prothrombin activation and accelerated fibrin formation in plasma.",
            "output": [
                "Do histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells?"
            ]
        },
        {
            "id": "task847-fe96f9f9d08045189dcc0bf2796a3e8f",
            "input": "Paraquat, a quaternary nitrogen herbicide, is a highly toxic prooxidant resulting in multi-organ failure including the heart although the underlying mechanism still remains elusive. This study was designed to examine the role of the cellular fuel sensor AMP-activated protein kinase (AMPK) in paraquat-induced cardiac contractile and mitochondrial injury.', 'Wild-type and transgenic mice with overexpression of a mutant AMPK \u03b12 subunit (kinase dead, KD), with reduced activity in both \u03b11 and \u03b12 subunits, were administered with paraquat (45 mg/kg) for 48 h. Paraquat elicited cardiac mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic diameter and reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, reduced cell survival, and overt mitochondrial damage (loss in mitochondrial membrane potential). In addition, paraquat treatment promoted phosphorylation of AMPK and autophagy. Interestingly, deficiency in AMPK attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) derangement. The beneficial effect of AMPK inhibition was associated with inhibition of the AMPK-TSC-mTOR-ULK1 signaling cascade. In vitro study revealed that inhibitors for AMPK and autophagy attenuated paraquat-induced cardiomyocyte contractile dysfunction.",
            "output": [
                "Does aMP-activated protein kinase deficiency rescue paraquat-induced cardiac contractile dysfunction through an autophagy-dependent mechanism?"
            ]
        },
        {
            "id": "task847-ef1551f22198435d8bf9aecfe079f227",
            "input": "Tyrosinase, the rate-limiting enzyme required for melanin production, has been targeted to develop active brightening/lightening materials for skin products. Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibiting quasi-drug, rhododendrol.', 'To investigate the mechanism underlying the depigmentation caused by rhododendrol-containing cosmetics, this study was performed.', 'The mechanism above was examined using more than dozen of melanocytes derived from donors of different ethnic backgrounds. The RNAi technology was utilized to confirm the effect of tyrosinase to induce the cytotoxicity of rhododendrol and liquid chromatography-tandem mass spectrometry was introduced to detect rhododendrol and its metabolites in the presence of tyrosinase.', 'Melanocyte damage was related to tyrosinase activity at a certain threshold. Treatment with a tyrosinase-specific siRNA was shown to dramatically rescue the rhododendrol-induced melanocyte impairment. Hydroxyl-rhododendrol was detected only in melanocytes with higher tyrosinase activity. When an equivalent amount of hydroxyl-rhododendrol was administered, cell viability was almost equally suppressed even in melanocytes with lower tyrosinase activity.",
            "output": [
                "Is depigmentation caused by application of the active brightening material , rhododendrol , related to tyrosinase activity at a certain threshold?"
            ]
        },
        {
            "id": "task847-a25942a9bcdf4082b2d4e917a30e7d1e",
            "input": "How has adherence been measured in recent prospective studies focusing on adherence to exercise programs among older people? What is the range of adherence rates? Which factors are associated with better adherence?', 'Systematic review of prospective studies that had a primary aim of assessing adherence to exercise programs.', 'Older people undertaking exercise programs.', 'Exercise programs.', 'Measures of adherence, adherence rates and factors associated with adherence.', 'Nine eligible papers were identified. The most common adherence measures were the proportion of participants completing exercise programs (ie, did not cease participation, four studies, range 65 to 86%), proportion of available sessions attended (five studies, range 58 to 77%) and average number of home exercise sessions completed per week (two studies, range 1.5 to 3 times per week). Adherence rates were generally higher in supervised programs. The person-level factors associated with better adherence included: demographic factors (higher socioeconomic status, living alone); health status (fewer health conditions, better self-rated health, taking fewer medications); physical factors (better physical abilities); and psychological factors (better cognitive ability, fewer depressive symptoms).",
            "output": [
                "Is adherence to exercise programs for older people influenced by program characteristics and personal factors : a systematic review?"
            ]
        },
        {
            "id": "task847-cb75ad9209e149ac88a06863ff7ba96a",
            "input": "Proteins containing the SPX (SYG1/Pho81/XPR1) domain are vital components in the phosphorus (P) signalling pathway, and regulate phosphate (Pi) homeostasis in plants. However, the characteristics and functions of GmSPX members in soybean (Glycine max) remain largely unknown.', 'BLAST searching revealed nine GmSPX members in the soybean genome. Subsequently, expression patterns of GmSPX members were investigated in various tissues of soybean grown in nutrient solution or sand culture through quantitative real-time PCR (qPCR) analysis. Sub-cellular localization of GmSPX was examined via transient expression of 35S:GmSPX-GFP in epidermal cells of onion (Allium cepa). Finally, soybean transgenic composite plants were generated to study GmSPX3 functions.', 'Nine GmSPX members were identified, which were classified into three groups based on phylogenetic analysis. Diverse responses of GmSPX members to deficiencies of nutrients (nitrogen, phosphorus, potassium and iron) or inoculation of arbuscular mycorrhizal fungi and rhizobia were observed in soybean. In addition, variations of sub-cellular localization of GmSPX members were found. Among them, GmSPX3, GmSPX7 and GmSPX8 were localized in the nuclei, and the other GmSPX members were confined to the nuclei and cytoplasm. The nuclear-localized and Pi starvation responsive-gene, GmSPX3, was functionally analysed in soybean transgenic composite plants. Overexpression of GmSPX3 led to increased P concentrations in both shoots and roots in the high-P treatment, and increased transcription of seven Pi starvation-responsive genes in soybean hairy roots.",
            "output": [
                "Does comparative characterization of GmSPX members reveal that GmSPX3 is involved in phosphate homeostasis in soybean?"
            ]
        },
        {
            "id": "task847-5de051453b264a8e9038f36bd36f5b9c",
            "input": "Endoscopic snare papillectomy (ESP) is a viable alternative to surgical treatment of ampullary adenomas and T1N0 stage ampullary carcinomas. The main drawback of this technique is the high risk of acute pancreatitis post procedure.The aim of this study was to assess the efficacy, safety, and long-term results of this procedure, and to determine whether routine pancreatic intubation facilitated by intraductal methylene blue (MB) injection reduces the risk for pancreatitis.', 'Between 2004 and 2011, 56 consecutive patients underwent ESP. Before resection, the pancreatic duct was cannulated, and MB was injected intraductally to facilitate stent placement after ampullectomy.', 'ESP was performed en bloc in 45 patients with histological findings of low-grade dysplasia (39%), high-grade dysplasia (25%), carcinoma (32.5%), and others (3.5%). The morbidity rate was 19.5%: acute pancreatitis (n=6), bleeding (n=4), perforation (n=1), and sepsis (n=1). Pancreatic intubation was performed in 89% of the patients. Postprocedure pancreatitis occurred significantly less in the patients with a pancreatic stent than in those without: 3/49 versus 3/6, P=0.013. ESP was considered as curative in 39 patients (75%). Of the 12 recurrences (25%), 10 were managed endoscopically, but with higher morbidity (acute pancreatitis=40%).",
            "output": [
                "Does pancreatic intubation facilitated by methylene blue injection decrease the risk for postpapillectomy acute pancreatitis?"
            ]
        },
        {
            "id": "task847-a550af18d2fb4500ba7f05de81cc96f4",
            "input": "To observe the effects of metastasis-associated tumor gene family 2 (MTA2) depletion on human breast cancer cell proliferation and metastasis.', 'A short-hairpin RNA targeting MTA2 was chemically synthesized and transfected into a lentivirus to construct Lv-shMTA2 for infection into the MDA-MB231 human breast cancer cell line. At 48 hours after infection cells were harvested and mRNA and protein levels of MTA2 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell viability and metastasis were assessed by CCK-8, wound-healing assay and Transwell assay, respectively. In addition, a xenograft model of human breast cancer was constructed to investigate cancerous cell growth and capacity for metastasis.', 'After infection with Lv-shMTA2, mRNA and protein levels of MTA2 was significantly reduced (p<0.05) and MDA-MB231 cell proliferation and metastasis were inhibited (p<0.05). In addition, mean tumor size was smaller than that in control group nude mice (p<0.05) and numbers of metastatic deposits in lung were lower than in control group mice (p<0.05). Depletion of MTA2 affected MMP-2 and apoptosis-related protein expression.",
            "output": [
                "Does short-hairpin RNA-mediated MTA2 silencing inhibit human breast cancer cell line MDA-MB231 proliferation and metastasis?"
            ]
        },
        {
            "id": "task847-228b60fa8ece4d5ea1dc31e3f5ef5c5b",
            "input": "We investigated the effects of dietary calcium (Ca) and magnesium (Mg) intakes on cardiovascular disease risks in older patients with diabetes.', 'In this cross-sectional study, 197 patients with type 2 diabetes aged 65\\xa0years and above were recruited. The 24-h dietary recalls and 1-week self-reported typical dietary intake patterns were collected. The Ca and Mg intakes of <67% of the recommended dietary allowance (RDA), 67%-100% of RDA, and >100% of RDA were defined as low, moderate, and high Ca and Mg intakes, respectively. Anthropometric measurements were determined and biochemical analysis of blood and urine was performed.', 'Our data indicated that 60.9% and 87.3% of our patients were Ca and Mg intakes below RDA, respectively. Patients whose Ca intake was high or low (81.2%) had significantly higher C-reactive protein (CRP) than those whose Ca intake was moderate (p\\u2009=\\u20090.043). Furthermore, patients whose Mg intake was low (87.3%) had significantly higher CRP than that of those who took adequate Mg (p\\u2009=\\u20090.025). The dietary Ca:Mg intake ratios were highly correlated with CRP, platelet counts, and red blood cell distribution (p\\u2009<\\u20090.05). A dietary Ca:Mg intake ratio of 2.0-2.5 was significantly correlated to lower CRP levels (p\\u2009=\\u20090.013).",
            "output": [
                "Does high or low calcium intake increase cardiovascular disease risks in older patients with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-c401c888f7e24213a9ff1d7ae961abc6",
            "input": "Recent studies evaluated the disease-modifying properties of lithium in mild cognitive impairment and dementia. Although potentially effective for these purposes, chronic lithium use in regard to safety in the elderly needs to be better explored.', 'To evaluate the effect of long-term lithium treatment at subtherapeutic doses on renal function in older adults. Secondary aims were to evaluate the clinical safety and tolerability of this treatment and its effects on thyroid, immune, and glycemic functions.', 'Between February 2007 and October 2011, a 2-year randomized, double-blind, placebo-controlled trial followed by a single-blinded phase for an additional 2 years. Sixty-one patients with mild cognitive impairment (Mayo Clinic criteria) were randomized to receive lithium or placebo. Renal function was estimated by the abbreviated Modification of Diet in Renal Disease (aMDRD) and the Chronic Kidney Disease-Epidemiology study (CKD-EPI) equations. Leukocytes, serum thyroid-stimulating hormone (TSH) and free thyroxine (T\u2084), and serum glucose and insulin were determined. Tolerability was evaluated at 3-month intervals through systematic clinical examinations and by the UKU Side Effect Rating Scale.', 'Analysis of longitudinal regression indicated that no significant changes in renal function were detected by the aMDRD (P = .453) and CKD-EPI (P = .213) equations after 4 years of lithium treatment. Significant increases in the number of neutrophils (P = .038), serum TSH (P = .034), and body weight (P = .015) were observed in the lithium group. The lithium group presented more overall adverse events (P = .045), particularly interfering in daily activities (P < .001). In addition, those patients had a higher incidence of diabetes mellitus (P = .037) and arrhythmia (P = .028).",
            "output": [
                "Does long-term , low-dose lithium treatment impair renal function in the elderly : a 2-year randomized , placebo-controlled trial followed by single-blind extension?"
            ]
        },
        {
            "id": "task847-4b7c26e0f7c4474eb32728b840b3cf65",
            "input": "To describe genomic imbalances in plasmacytoid urothelial carcinoma (PUC), which is a rare and aggressive variant of urothelial carcinoma (UC).', 'In total, 25 formalin-fixed paraffin-embedded PUCs were analyzed by metaphase comparative genomic hybridization. Genomic imbalances were considered to be characteristic if they were detected in \u2265 20% of the cases. Chromosome regions deviating by \u2265 3 standard deviations from the average chromosome profile were scored as chromosomal gains or losses. Copy-number variations (CNVs) of CDH1 (16q 22.1), SNAI1 (20q 13.1), CCND1 (11q13.3), ERBB2 (17q12), and FOXO3 (6q21) were validated using quantitative polymerase chain reaction.', 'Chromosomal aberrations were detected in every PUC analyzed, and the average number of aberrations was 10.24 (ranging from 1-15). Characteristic aberrations were gains on 1q (48%), 3p (20%), 6p (32%), 11q (72%), 15q (36%), 16q (44%), 17p (76%), 17q (88%), and 20q (88%) and losses on 2q (24%) 4p (36%), 4q (84%), 5q (44%), 6q (68%), 13q (20%), and Xq (52%). polymerase chain reaction-based analysis of CNV for CCND1 (11q13) showed a deletion in 73% of the cases. CDH1 (16q22) was deleted in 72% and amplified in 5%. ERBB2 (17q12) displayed remarkably few copy-number alterations, with only 14% showing an amplification. SNAI1 (20q13) showed reduced gene copy numbers in 59.1% of the cases, whereas no copy-number gains were detected. FOXO3 (6q21) exhibited the lowest number of copy-number alterations, with 9% of all cases showing an amplification.",
            "output": [
                "Does comparative genomic hybridization show complex genomic changes of plasmacytoid urothelial carcinoma?"
            ]
        },
        {
            "id": "task847-1da64a2b181a4ef08aaea022c5897153",
            "input": "Patients with schizophrenia have substantially reduced subjective well-being (SW) compared to healthy individuals. It has been suggested that diminished SW may be related to deficits in the neural processing of reward but this has not been shown directly. We hypothesized that, in schizophrenia, lower SW would be associated with attenuated reward-related activation in the reward network.', 'Twenty patients with schizophrenia with a range of SW underwent a functional magnetic resonance imaging (fMRI) reward task. The brain activity underlying reward anticipation and outcome in schizophrenia was examined and compared to that of 12 healthy participants using a full factorial analysis. Region of interest (ROI) analyses of areas within the reward network and whole-brain analyses were conducted to reveal neural correlates of SW.', 'Reward-related neural activity in schizophrenia was not significantly different from that of healthy participants; however, the patients with schizophrenia showed significantly diminished SW. Both ROI and whole-brain analyses confirmed that SW scores in the patients correlated significantly with activity, specifically in the dorsal anterior cingulate cortex (dACC), during both reward anticipation and reward outcome. This association was not seen in the healthy participants.",
            "output": [
                "Is impaired subjective well-being in schizophrenia associated with reduced anterior cingulate activity during reward processing?"
            ]
        },
        {
            "id": "task847-106ab58d0564478fb4cf1544a1e58066",
            "input": "Microsomal prostaglandin E synthase-2 (mPGES-2) deletion does not influence in vivo PGE2 production and the function of this enzyme remains elusive. The present study was undertaken to investigate the role of mPGES-2 in streptozotocin (STZ)-induced type-1 diabetes and organ injuries.', 'mPGES-2 wild type (WT) and knockout (KO) mice were treated by a single intraperitoneal injection of STZ at the dose of 120 mg/kg to induce type-1 diabetes. Subsequently, glycemic status and organ injuries were evaluated.', 'Following 4 days of STZ administration, mPGES-2 KO mice exhibited severe lethality in contrast to the normal phenotype observed in WT control mice. In a separate experiment, the analysis was performed at day 3 of the STZ treatment in order to avoid lethality. Blood glucose levels were similar between STZ-treated KO and WT mice. However, the livers of KO mice were yellowish with severe global hepatic steatosis, in parallel with markedly elevated liver enzymes and remarkable stomach expansion. However, the morphology of the other organs was largely normal. The STZ-treated KO mice displayed extensive hepatocyte apoptosis compared with WT mice in parallel with markedly enhanced inflammation and oxidative stress. More interestingly, a liver-specific 50% upregulation of GLUT2 was found in the KO mice accompanied with a markedly enhanced STZ accumulation and this induction of GLUT2 was likely to be associated with the insulin/SREBP-1c pathway. Primary cultured hepatocytes of KO mice exhibited an increased sensitivity to STZ-induced injury and higher cellular STZ content, which was markedly blunted by the selective GLUT2 inhibitor phloretin.",
            "output": [
                "Does mPGES-2 deletion remarkably enhance liver injury in streptozotocin-treated mice via induction of GLUT2?"
            ]
        },
        {
            "id": "task847-6704a8af89a74f76aa1bdbb805cf4add",
            "input": "We treated patients experiencing drug-eluting stent (DES) restenosis with plain old balloon angioplasty (POBA), implantation of the same type of DES [homogeneous drug-eluting stent (HOMO-DES)], or implantation of a different type of DES [heterogeneous drug-eluting stent (HETERO-DES)], and compared the efficacy and safety of these procedures for the prevention of repeated in-stent restenosis (ISR).', 'In patients with de-novo coronary lesions, DES implantation is associated with a markedly reduced restenosis rate as compared with that associated with a bare metal stent and POBA. However, the optimal management strategy for patients with DES ISR remains unknown.', 'We identified 191 consecutive DES ISR lesions from 183 patients who required clinically driven revascularization and divided them into three groups according to the treatment: 38 lesions were treated with POBA, 38 with HOMO-DES, and 115 with HETERO-DES.', 'The incidence of target lesion revascularization (TLR) was 42.1% (16/38), 15.8% (6/38), and 16.5% (19/115) in the POBA, HOMO-DES, and HETERO-DES groups (POBA vs. HOMO, HETERO-DES; P=0.002, respectively). Multivariate analysis indicated that diabetes [odds ratio (OR), 3.4], hemodialysis (OR, 7.74), nonfocal ISR patterns (OR, 3.35), previous myocardial infarction (OR, 3.26), and POBA (OR, 8.84) were independent predictors of TLR.",
            "output": [
                "Does switching types of drug-eluting stents prevent repeated in-stent restenosis in patients with coronary drug-eluting stent restenosis?"
            ]
        },
        {
            "id": "task847-e6c90962fb8247fd9ba1e478a8dfc5df",
            "input": "Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D.', 'We studied 1142 youth with incident T1D, who had at least two fasting lipid measurements over 2 yr (initial visit mean: age = 10.8 \u00b1 3.9 yr, BMIz = 0.55 \u00b1 0.97, T1D duration = 10.7 \u00b1 7.6 months; 47.5% female, 77.9% non-Hispanic white) in the SEARCH for Diabetes in Youth Study. Longitudinal mixed models were used to examine the relationships between changes in BMIz and changes in total, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, and log triglycerides (TG) adjusted for initial age, sex, race/ethnicity, clinical site, season of study visit, T1D duration, and glycated hemoglobin A1c (HbA1c).', 'We found that over 2 yr all lipid levels, except LDL-C, increased significantly (p < 0.05). Decreases in BMIz were associated with favorable changes in HDL-C and TG only and the magnitude of these changes depended on the initial BMIz value (interaction p < 0.05), so that greater improvements were seen in those with higher BMIz.",
            "output": [
                "Does change in adiposity minimally affect the lipid profile in youth with recent onset type 1 diabetes?"
            ]
        },
        {
            "id": "task847-187dcb26e5bd4b4aa0ab51a8fae10bc3",
            "input": "Endoscopic volume reduction of the stomach may provide a minimally invasive alternative for surgical procedures in the treatment of obesity.', 'To assess safety and preliminary effectiveness in the first human application of a novel endoscopic stapling technique.', 'Prospective, observational, phase 1 study.', 'Two university hospitals in The Netherlands.', 'Patients with a body mass index (BMI) of 40 to 45 kg/m(2) or 30 to 39.9 kg/m(2) with obesity-related comorbidity.', 'Gastric volume reduction with an endoscopic stapler.', 'Primary outcome measure was the prevalence of serious or mild adverse events. Reduction of excess body weight after 12 months was assessed as a secondary outcome measure for effectiveness of the procedure.', 'Seventeen patients with a median BMI of 40.2 kg/m(2) (interquartile range [IQR] 37.6-42.8) underwent an endoscopic stapling procedure. Median procedure time was 123 minutes (IQR 95-129). No serious adverse events occurred. Adverse events were gastric pain (n\\xa0= 7, range 1-3 days), sore throat (n\\xa0= 4, 2-3 days), diarrhea (n\\xa0= 4, 2-15 days), nausea (n\\xa0= 3, 2-4 days), constipation (n\\xa0= 4, 3-14 days), and vomiting (n\\xa0= 3, 1-4 days). All adverse events were mild and resolved with conservative treatment within 15 days after surgery. The median percentage excess weight loss in the first year was 34.9% (IQR 17.8-46.6).",
            "output": [
                "Is endoscopic gastric volume reduction with a novel articulating plication device safe and effective in the treatment of obesity ( with video )?"
            ]
        },
        {
            "id": "task847-66a92f14a2814f018fdfbefdb2eda665",
            "input": "The association between environmental lead exposure and blood pressure variability, an important risk factor for cardiovascular disease, is unexplored and unknown. The objective of the study was to test the hypothesis that lead exposure is associated with blood pressure variability.', \"American participants 17 years of age or older from National Health and Nutrition Examination Survey III were included in the analysis. Participants' blood lead concentrations expressed as micrograms per deciliter were determined. The standard deviations of visit-to-visit systolic and diastolic blood pressure were calculated to determine blood pressure variability. Multivariable regression analyses adjusted for age, gender, race, smoking and socioeconomic status were employed.\", \"The participants' mean age and mean blood lead concentration were 42.72 years and 3.44 mcg/dl, respectively. Systolic blood pressure variability was significantly associated with environmental lead exposure after adjusting for the effect of the confounders. The unadjusted and adjusted means of visit-to-visit systolic blood pressure variability and the \u03b2 coefficient of lead exposure were 3.44, 3.33 mcg/dl, \u03b2 coefficient = 0.07, P < 0.01.",
            "output": [
                "Is environmental lead exposure associated with visit-to-visit systolic blood pressure variability in the US adults?"
            ]
        },
        {
            "id": "task847-316c23a225dd4773a709550a4ecb1477",
            "input": "Few studies investigated the relationship between fibrinolysis abnormalities and residual pulmonary perfusion defects after acute pulmonary embolism (PE).', 'To assess the fibrinolytic profile in patients with prior PE in relation to the extent of scintigraphically detectable residual perfusion abnormalities.', 'We studied 71 consecutive patients with a prior episode of PE, who were examined after one year of the incident embolic event, and at least one month after anticoagulation withdrawal. They underwent lung scintigraphy to assess the recovery of pulmonary perfusion, echocardiography and chest radiography to look for signs of pulmonary hypertension. Clot formation and lysis were evaluated by two turbidimetric methods: Clot and Lysis Assay and Clot Lysis Time. We also measured the in vitro plasmin-mediated lysis of fibrin from purified fibrinogen, and the circulating levels of fibrinolytic inhibitors. The sample was split in two categories based on the extent of residual perfusion defects: <10% (n=53), \u2265 10% (n=18).', 'Patients with perfusion defects >10% had significantly longer lysis time (p<0.05), and higher levels of plasminogen activator inhibitor-1 (p<0.01) than those with perfusion defects <10%. The time interval between symptoms onset and PE diagnosis (time-to-diagnosis) was significantly longer in patients with perfusion defects >10% than in the others (p=0.005). In multivariate logistic regression, both lysis time and time-to-diagnosis were independently associated with perfusion defects >10% (p<0.001). None of the sampled patients had echocardiographic or radiologic signs of pulmonary hypertension.",
            "output": [
                "Are residual perfusion defects in patients with pulmonary embolism related to impaired fibrinolytic capacity?"
            ]
        },
        {
            "id": "task847-79e31749db3b455996f85a9889f76998",
            "input": "Pancreatic neuroendocrine tumors (PNETs) are a group of rare tumors. Chromogranin A (CgA) was considered as the most practical and useful serum tumor marker in PNET patients. But peripheral blood levels of CgA are not routinely tested in Chinese patients with PNETs. This study was to assess the diagnostic value of CgA in Chinese patients with PNETs especially in patients with insulinomas.', 'Eighty-nine patients with PNETs including 57 insulinomas and 32 non-insulinoma PNETs as well as 86 healthy participants were enrolled in this study between September 2003 and June 2013. Serum levels of CgA were measured by ELISA method. Expression of CgA protein was detected in 26 PNET tissues including 14 insulinomas by immunohistochemical staining.', 'Serum levels of CgA in 89 PNET patients were significantly higher than that in healthy controls (P\\u2009=\\u20097.2\\u2009\u00d7\\u200910-9). Serum levels of CgA in 57 patients with insulinomas (median 64.8\\xa0ng/ml, range 25-164) were slightly higher than the levels in healthy controls (median 53.4\\xa0ng/ml, range 39-94) but much lower than the levels in 32 patients with non-insulinoma PNETs (median 193\\xa0ng/ml, range 27-9021), P\\u2009=\\u20090.001. The serum CgA levels were reduced in 16 of 17 patients with insulinomas after tumor resection. ROC curve showed that CgA values at 60\\xa0ng/ml distinguished patients with insulinomas from healthy controls but its sensitivity and specificity were 66.7% and 73.3%, respectively. In contrast, CgA values at 74\\xa0ng/ml distinguished patients with non-insulinoma PNETs from healthy controls, and the sensitivity and specificity were 65.6% and 91.9%, respectively. Except for two insulinomas with negative staining of CgA, 12 insulinoma tissues showed positive staining of CgA.",
            "output": [
                "Is chromogranin A a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas?"
            ]
        },
        {
            "id": "task847-37463a998ead43c28fa4d3318f9e626e",
            "input": "A disintegrin and metalloprotease 8 (ADAM8) has been reported to be associated with various malignancies. However, no studies have examined ADAM8 association in colorectal cancer (CRC). The aim of this study was to investigate the expression and function of ADAM8 in CRC.', 'Expression level of ADAM8 in CRC was evaluated by quantitative RT-PCR, western blot and immunohistochemical staining analysis. The role of ADAM8 in colorectal carcinogenesis was evaluated by in vitro assays. The correlations between ADAM8 status and clinicopathological features including survival were analyzed.', 'ADAM8 was highly expressed in CRC tissues compared with adjacent normal tissues. Knockdown of ADAM8 in two CRC cell lines resulted in reduced cellular growth and proliferation, and increased apoptosis. Immunohistochemistry analysis showed no significant correlations of ADAM8 protein expression with clinicopathologic features. Survival analysis indicated that patients with ADAM8-positive tumors had worse 5-year overall survival (OS, p = 0.037) and 5-year disease free survival (DFS, p = 0.014) compared with those with ADAM8-negative tumors. Multivariate analysis indicated ADAM8 expression was an independent prognostic factor for both OS and DFS (both p< 0.001). Subgroup analysis showed that 5-year OS of colon cancer, T3-T4 stage and N0 stage was worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05). The 5-year DFS in colon cancer, T3-T4 stage, N0 stage, TNM stage II, adenocarcinoma, moderate differentiation and male patient subgroups was also worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05).",
            "output": [
                "Is expression of A disintegrin and metalloprotease 8 associated with cell growth and poor survival in colorectal cancer?"
            ]
        },
        {
            "id": "task847-8efcc979648949dc9b6139b43fcd9b8f",
            "input": "The aim of this study was to survey the relative importance of postoperative recovery targets and perioperative care items, as perceived by a large group of international dedicated professionals.', 'A questionnaire with eight postoperative recovery targets and 13 perioperative care items was mailed to participants of the first international Enhanced Recovery After Surgery (ERAS) congress and to authors of papers with a clear relevance to ERAS in abdominal surgery. The responders were divided into categories according to profession and region.', \"The recovery targets 'To be completely free of nausea', 'To be independently mobile' and 'To be able to eat and drink as soon as possible' received the highest score irrespective of the responder's profession or region of origin. Equally, the care items 'Optimizing fluid balance', 'Preoperative counselling' and 'Promoting early and scheduled mobilisation' received the highest score across all groups.",
            "output": [
                "Is functional recovery considered the most important target : a survey of dedicated professionals?"
            ]
        },
        {
            "id": "task847-d347dfe64ab944e387c6129f1ae39193",
            "input": "Exposure to hypoxia has been suggested to acutely alter glucose regulation. However, the effects of successive exposure to moderate hypoxia on postprandial glucose regulation and substrate oxidation pattern after multiple meals have not been elucidated.', 'We examined the effects of successive exposure to moderate hypoxia on metabolic responses and substrate oxidation pattern.', 'Eight healthy men (21.0\\u2009\u00b1\\u20090.6\\xa0yrs, 173\\u2009\u00b1\\u20092.3\\xa0cm, 70.6\\u2009\u00b1\\u20095.0\\xa0kg, 23.4\\u2009\u00b1\\u20091.1\\xa0kg/m(2)) completed two experimental trials on separate days: a rest trial under normoxic conditions (FiO2\\u2009=\\u200920.9%) and a rest trial under hypoxic conditions (FiO2\\u2009=\\u200915.0%). Experimental trials were performed over 7\\xa0h in an environmental chamber. Blood and respiratory gas samples were collected over 7\\xa0h. Standard meals were provided 1\\xa0h (745\\xa0kcal) and 4\\xa0h (731\\xa0kcal) after entering the chamber.', 'Although each meal significantly increased blood glucose and serum insulin concentrations (P\\u2009<\\u20090.05), these responses did not differ significantly between the trials. There were no significant differences in areas under the curves for glucose or insulin concentrations over 7\\xa0h between the trials. No significant differences were observed in blood lactate, serum cortisol, free fatty acid, or glycerol concentrations over 7\\xa0h between the trials. The oxygen consumption ( [Formula: see text]) and carbon dioxide production ( [Formula: see text]) 3\\xa0h after entering the chamber were significantly higher in the hypoxic trial than in the normoxic trial (P\\u2009<\\u20090.05). However, the differences did not affect respiratory exchange ratio (RER). The average values of [Formula: see text], [Formula: see text], and RER did not differ between the trials.",
            "output": [
                "Does successive exposure to moderate hypoxia affect glucose metabolism and substrate oxidation in young healthy men?"
            ]
        },
        {
            "id": "task847-1d23cb7099744ce3a04b12b974504a30",
            "input": "Host genetic factors are thought to modulated the severity of disease caused by infection with the 2009 H1N1 pandemic influenza virus (H1N1pdm09). The human CCR5 gene encodes a cytokine receptor important for cell-mediated immune response against H1N1pdm09. A 32-bp polymorphic deletion in the coding sequence of CCR5, the so-called CCR5\u039432 allele, segregates in populations of European ancestry with a frequency of 8-15%. A high proportion of CCR5\u039432 heterozygotes was reported in a sample of white Canadian critically-ill H1N1pdm09 infected subjects, suggesting an association with disease severity.', 'We recruited 29 H1N1pdm09 infected subjects from Southern Europe (mostly Italians) with a wide clinical spectrum of disease symptoms; the sample included 7 subjects who developed acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. The CCR5\u039432 variant was genotyped in all subjects.', 'The CCR5\u039432 allele was found in one single subject, who developed a very mild form and was not hospitalized.",
            "output": [
                "Is the CCR5\u039432 allele a major predisposing factor for severe H1N1pdm09 infection?"
            ]
        },
        {
            "id": "task847-8e2b0339a1d3494daefc30631d463297",
            "input": "The dorsolateral prefrontal cortex (DLPFC) plays an important role in appetite and food intake regulation.', 'Because previous data revealed that transcranial direct current stimulation (tDCS) of the DLPFC reduces food cravings, we hypothesized that repetitive electric stimulation of the right DLPFC would lower food intake behavior in humans.', 'In a single-blind, code-based, placebo-controlled, counterbalanced, randomized crossover experiment, 14 healthy young men with body mass index (in kg/m(2)) from 20 to 25 were examined during 8 d of daily tDCS or a sham stimulation. After tDCS or sham stimulation on the first and the last day of both experimental conditions, participants consumed food ad libitum from a standardized test buffet.', 'One week of daily anodal tDCS reduced overall caloric intake by 14% in comparison with sham stimulation. Moreover, repetitive tDCS diminished self-reported appetite scores.",
            "output": [
                "Does repetitive electric brain stimulation reduce food intake in humans?"
            ]
        },
        {
            "id": "task847-8d72b99a4765421caffaaff9d5f849e3",
            "input": "The PI3K-AKT-mTOR (phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin) pathway plays a crucial role in a subset of advanced pancreatic neuroendocrine tumors (PanNETs). In breast and endometrial carcinoma, activation of this pathway inhibits progesterone receptor (PR) expression.', 'To determine whether combined low expression of PR and phosphatase and tensin homologue (PTEN), a negative regulator of the PI3K-AKT-mTOR pathway, is a prognostic factor.', 'A total of 160 resected PanNETs (89 low grade and 71 intermediate grade) were analyzed for PR and PTEN immunohistochemical positivity and staining was correlated with metastasis-free survival (MFS) and overall survival (OS). Progesterone receptor staining was scored as positive by using 1% or greater as cutoff. Weak/faint staining in greater than 90% of tumor cells was considered low PTEN positivity.', 'Most PanNETs (110 cases, 69%) were both PR and PTEN positive, 45 (28%) were either PR or PTEN positive, and only 5 (3%) had a PR-negative and PTEN-low profile. Combined PR-PTEN positivity was significantly associated with MFS in patients with stage I and II disease (P <.001) and OS in all patients (P < .001) and remained a significant predictor of survival after adjusting for other factors. Patients with PR-negative-PTEN-low PanNETs had the shortest median MFS and OS, compared to those with tumors that were either PR or PTEN positive and with tumors positive for both PR and PTEN (P \u2264 .001).",
            "output": [
                "Do progesterone receptor and PTEN expression predict survival in patients with low- and intermediate-grade pancreatic neuroendocrine tumors?"
            ]
        },
        {
            "id": "task847-a99b3a3be74d41dba65c97bf9f36c73c",
            "input": "Hif1p is an H3/H4-specific histone chaperone that associates with the nuclear form of the Hat1p/Hat2p complex (NuB4 complex) in the yeast Saccharomyces cerevisiae. While not capable of depositing histones onto DNA on its own, Hif1p can act in conjunction with a yeast cytosolic extract to assemble nucleosomes onto a relaxed circular plasmid.', 'To identify the factor(s) that function with Hif1p to carry out chromatin assembly, multiple steps of column chromatography were carried out to fractionate the yeast cytosolic extract. Analysis of partially purified fractions indicated that Hif1p-dependent chromatin assembly activity resided in RNA rather than protein. Fractionation of isolated RNA indicated that the chromatin assembly activity did not simply purify with bulk RNA. In addition, the RNA-mediated chromatin assembly activity was blocked by mutations in the human homolog of Hif1p, sNASP, that prevent the association of this histone chaperone with histone H3 and H4 without altering its electrostatic properties.",
            "output": [
                "Does the yeast histone chaperone hif1p function with RNA in nucleosome assembly?"
            ]
        },
        {
            "id": "task847-6a5060c8cb614a369710d5a329594d6b",
            "input": "In order to develop effective weight management strategies, it is important to identify factors that influence energy intake. Portion size has been discussed as one such factor. To date, most studies focusing on the relationship between portion size, energy intake, and weight have analyzed questionnaire data and 24-h records. In this study, we assessed the onset of satiety using the water-load test in normal-weight and obese children and adolescents.', '60 obese and 27 normal-weight children and adolescents aged between 9 and 17 years participated in the water load test which involved drinking water for 3 min or until feeling full. The amount of water consumed was recorded.', 'Obese children and adolescents drank 20% more water until the onset of satiety when compared with normal-weight participants (478\\u2009\u00b1\\u2009222 ml vs. 385\\u2009\u00b1\\u2009115 ml, P\\u2009<\\u20090.05).",
            "output": [
                "Do obese children and adolescents need increased gastric volumes in order to perceive satiety?"
            ]
        },
        {
            "id": "task847-0b3c87a766684935897f7a060e7cf1ba",
            "input": "We hypothesized that preconditioning (PC) with a short exposure to isoflurane (ISO) would reduce neurodegeneration induced by prolonged exposure to ISO in neonatal rats, as previously shown in neuronal cell culture.', 'We randomly divided 7-day-old Sprague-Dawley rats into 3 groups: control, 1.5% ISO, and PC + 1.5% ISO. The control group was exposed to carrier gas (30% oxygen balanced in nitrogen) for 30 minutes and then to carrier gas again for 6 hours the following day. The 1.5% ISO group was exposed to carrier gas for 30 minutes and then to 1.5% ISO for 6 hours the following day. The PC + 1.5% ISO group was preconditioned with a 30-minute 1.5% ISO exposure and then exposed to 1.5% ISO for 6 hours the following day. Blood and brain samples were collected 2 hours after the exposures for determination of neurodegenerative biomarkers, including caspase-3, S100\u03b2, caspase-12, and an autophagy biomarker Beclin-1.', 'Prolonged exposure to ISO significantly increased cleaved caspase-3 expression in the cerebral cortex of 7-day-old rats compared with the group preconditioned with ISO and the controls using Western blot assays. However, significant differences were not detected for other markers of neuronal injury.",
            "output": [
                "Does anesthetic preconditioning inhibit isoflurane-mediated apoptosis in the developing rat brain?"
            ]
        },
        {
            "id": "task847-caa4306c359f41d1b6d76247d3f4d1be",
            "input": "Complement Factor I (CFI) and the CD46 complement regulator (CD46) play an important role in the complement activation pathways, which is known to affect the development of uveitis. The present study was performed to investigate the association of the CFI and CD46 genes with acute anterior uveitis (AAU).', 'A total of 600 subjects (300 patients with AAU and 300 healthy controls) were recruited for this case-control study. Six CFI single nucleotide polymorphisms (SNP) (rs7356506, rs10029485, rs11726949, rs12512308, rs7438961, rs998538) and four CD46 SNPs (rs12138764, rs2466571, rs2796278, rs7545126) were genotyped using Sequenom MassARRAY technology. Allele and genotype frequencies were compared between patients and controls using the \u03c7(2) test. Analyses were stratified for gender, human leukocyte antigen (HLA)-B27, and ankylosing spondylitis status.', 'Rs7356506 in the CFI gene was found to be protective against AAU. There was a significant increase in the frequency of the A allele (p=0.003, pc=0.03, OR=0.684, CI 0.534 to 0.876) and AA homozygosity (p=0.004, pc=0.04, OR=0.624, CI 0.452 to 0.862) in AAU patients as compared to controls. Stratified analysis, according to gender and HLA-B27 status for AAU, also revealed the association with CFI-rs7356506. None of the tested SNPs of CD46 were associated with AAU.",
            "output": [
                "Is cFI-rs7356506 a genetic protective factor for acute anterior uveitis in Chinese patients?"
            ]
        },
        {
            "id": "task847-9cdd544d143f4b10a467e38441fcffda",
            "input": "Gamma glutamyl transpeptidase (GGT) is a membrane bound enzyme that plays a key role in the synthesis of the antioxidant glutathione. Epidemiological studies have linked high GGT with an increased risk of morbidity and cardiovascular mortality. In contrast, GGT is usually elevated in liver transplant recipients that experience good outcomes.', 'To study if and how GGT is correlated with mortality following liver transplantation.', 'We analyzed the prognostic relevance of serum GGT levels during the early and late postoperative period after liver transplantation in 522 consecutive adults. We also studied alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels.', 'Early after transplantation, the peak median (interquartile range) GGT levels were significantly higher in patients who survived more than 90 days compared to non-survivors: 293 (178-464) vs. 172 (84-239) U/l, p<0.0001. In contrast, late after transplantation, GGT levels were significantly lower in patients who survived more than 5 years than those who did not ( p<0.01). The pattern of GGT levels also differed from those of alanine aminotransferase, aspartate aminotransferase, and total bilirubin early after transplantation, while these patterns were congruent late after transplantation. Kaplan-Meier survival analysis showed that early after transplantation the higher the GGT levels, the better the 90-day survival ( p<0.001). In contrast, late after transplantation, higher GGT levels were associated with a lower 5-year survival ( p<0.001).",
            "output": [
                "Is early elevated serum gamma glutamyl transpeptidase after liver transplantation associated with better survival?"
            ]
        },
        {
            "id": "task847-c3e37ab9a13443aebac3f125ae13a4d7",
            "input": "This study describes a case of eye burn induced by sodium hypochlorite used as an irrigant during root canal preparation.', 'A 24-year-old female endodontist was using an operating microscope during root canal treatment, and as the root canal was irrigated, the pressure cannula burst and the irrigant (3.5% sodium hypochlorite) came into direct contact with her left eye. She immediately sought ophthalmologic emergency care for pain, redness of the cornea, burning sensation, photophobia, intraocular pressure, and blurred vision. The initial treatment consisted of washing the eye with saline solution and administering analgesic and anti-inflammatory (steroid) medications. One day after the accident, a topical demulcent and hydroxypropyl medication were applied to the eyeball (conjunctiva), the eye was bandaged for 24 hours, and rest was prescribed for 7 days. Eight days later, a corneal ulcer was diagnosed, and antibiotic and anti-inflammatory (steroid) medications were used.', 'Vision was restored without any sequelae 4 weeks after the accident. The endodontist was instructed to apply control medication (Lagricel; Sophia SA, Caracas, Venezuela) for 3 months and to return for ophthalmologic follow-up every 6 months.",
            "output": [
                "Do sodium hypochlorite chemical burn in an endodontist 's eye during canal treatment using operating microscope?"
            ]
        },
        {
            "id": "task847-79e4f0bc05864d54a5fba68461857e41",
            "input": "The use of fetal growth charts assumes that the optimal size at birth is at the 50(th) birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for perinatal mortality rates. The objective of this study was to investigate the distribution and timing (antenatal, intrapartum or neonatal) of perinatal mortality and morbidity in relation to birth weight and gestational age at delivery.', \"Data from over 1 million births occurring at 28-43\\u2009weeks' gestation from singleton pregnancies without congenital abnormalities in the period from 2002 to 2008 were collected from The Netherlands Perinatal Registry. The distribution of perinatal mortality according to birth-weight centile and gestational age at delivery was studied.\", \"In the 1\\u2009170\\u2009534 pregnancies studied, there were 5075 (0.43%) perinatal deaths. The highest perinatal mortality occurred in those with a birth weight below the 2.3(rd) centile (25.4/1000 births) and the lowest mortality was in those with birth weights between the 80(th) and 84(th) centiles (2.4/1000 births), according to routinely used growth charts. Antepartum deaths were lowest in those with birth weight between the 90(th) and 95(th) centiles. Data were almost identical when the analysis was restricted to infants born at \u2265\\u200937\\u2009weeks' gestation.",
            "output": [
                "Is human fetal growth constrained below optimal for perinatal survival?"
            ]
        },
        {
            "id": "task847-b1cf9435d8374896841778d1feccb592",
            "input": "WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc's anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats.\", 'Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation.', 'Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1\u03b2 and TNF-\u03b1 cytokines to control levels.",
            "output": [
                "Does zinc treatment ameliorate diarrhea and intestinal inflammation in undernourished rats?"
            ]
        },
        {
            "id": "task847-cd91c801e56247a196e1840211c310be",
            "input": "Silibinin exerts hepatoprotective, anti-inflammatory and anti-fibrotic effects. Several pre-clinical studies have shown anti-tumoral activity of silibinin in breast cancer cell lines.', \"We present the case of a heavily pre-treated breast cancer patient with extensive liver infiltration. The patient presented with progressive liver failure despite several chemotherapy treatments, including paclitaxel, capecitabine and vinorelbine. After four cycles of a fourth-line chemotherapy treatment consisting of carboplatin and gemcitabine, the patient's liver blood test results deteriorated to life-threatening levels. The compassionate use of Legasil\u00ae, a new commercially available nutraceutical product containing a new silibinin formulation, was offered to the patient according to article 37 of the 2013 Declaration of Helsinki. After treatment initiation, the patient presented clinical and liver improvement, which permitted the patient to continue palliative chemotherapy.",
            "output": [
                "Does silibinin administration improve hepatic failure due to extensive liver infiltration in a breast cancer patient?"
            ]
        },
        {
            "id": "task847-e594f8f871434698b504176b125d8422",
            "input": "The prevalence of meticillin-resistant Staphylococcus aureus (MRSA) in Norway is low but increasing. Over the last decade, numerous nursing homes have experienced MRSA outbreaks. One genetic lineage, spa type t304, has been identified at multiple nursing homes and has caused large outbreaks lasting for several years.', 'To evaluate whether spa typing is sufficient for the detection of MRSA spread and endemic establishment in a low-prevalence area, using spa type t304 as the test organism.', 'All spa type t304 isolates detected in 1991-2010 in the most densely populated area of Norway were included. Time and place of bacterial sampling were recorded. The isolates were analysed using multi-locus sequence typing, staphylococcal cassette chromosome mec typing, detection of lukS/F-PV and pulsed-field gel electrophoresis (PFGE).', 'In total, 181 spa type t304 isolates were identified in three of 23 municipalities. Most (91%) of the isolates could be linked to 13 nursing homes, eight of which experienced outbreaks. PFGE analysis revealed three PFGE types, consisting of 19 PFGE patterns; 95% of the isolates were PFGE type 2. In total, PFGE types 2 and 3 accounted for 99% of all nursing home isolates, and included isolates from different nursing homes, different outbreaks and different time periods. Additional genetic analyses did not further differentiate between the spa type t304 isolates.",
            "output": [
                "Is spa typing alone sufficient to demonstrate endemic establishment of meticillin-resistant Staphylococcus aureus in a low-prevalence country?"
            ]
        },
        {
            "id": "task847-5a6bf0c73c864eb490db5743b86b045c",
            "input": "Oxidative stress can result in damage to the brain and other organs. To protect from oxidative damage, the human body possesses molecular defense systems, based on the activity of antioxidants, and enzymatic defense systems, including the enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Although pre-clinical research has shown that stimulant use is associated with oxidative damage, oxidative stress and the antioxidant defense systems have not been evaluated in clinical samples of stimulant-dependent patients.', 'This study aimed to investigate the link between stimulant dependence and oxidative stress.', 'Peripheral blood samples from 174 methamphetamine (n = 48) and/or cocaine-dependent (n = 126) participants as well as 30 normal control participants were analyzed for the enzyme activities of CAT, SOD, and GSH-Px in the erythrocytes and the total antioxidant capacity and the malondialdehyde concentration in the plasma.', 'We could show an association of stimulant dependence with a depletion of total antioxidant capacity to 54.6 \u00b1 4.7%, which correlates with a reduced activity of the SOD to 71.3 \u00b1 0.03% compared with healthy control participants (100%).",
            "output": [
                "Is total antioxidant capacity significantly lower in cocaine-dependent and methamphetamine-dependent patients relative to normal controls : results from a preliminary study?"
            ]
        },
        {
            "id": "task847-b58006ef3ba04c7b82945554744ceb24",
            "input": "Pathophysiological mechanisms associated with neoplastic progression in patients with short-segment Barrett's oesophagus (SSBO), who represent the vast majority of the Barrett population, have not been defined.\", 'To evaluate pathophysiological characteristics of patients with SSBO and dysplasia detected at 3-year surveillance endoscopy (incident dysplasia).', 'Patients with SSBO underwent impedance-pH monitoring during heartburn-suppressing PPI therapy. Fifteen patients (12 males, median age 62 years) with incident dysplasia and 50 patients (43 males, median age 59 years) without dysplasia were compared. Impedance-pH parameters, including chemical clearance assessed by the post-reflux swallow-induced peristaltic wave (PSPW) index, were evaluated.', 'All patients declared persisting heartburn suppression on maintenance PPI therapy at 3-year follow-up, 58/65 (89%) with standard dosages. The median gastric and oesophageal acid exposure time (GAET and OAET) did not differ between patients with and without incident dysplasia at the time of surveillance (36% and 0.6% vs. 33% and 0.5%) or index endoscopy (33% and 0.3% vs. 41% and 0.5%) (P > 0.05). Contrastingly, the median PSPW index was significantly lower in patients with than in patients without incident dysplasia at the time of surveillance (15%, vs. 32%) and index endoscopy (12% vs. 30%) (P = 0.001). The PSPW index, the GAET and the OAET did not vary over time (P > 0.05). A PSPW index <26% was predictive of incident dysplasia with a 75% accuracy.",
            "output": [
                "Is neoplastic progression in short-segment Barrett 's oesophagus associated with impairment of chemical clearance , but not inadequate acid suppression by proton pump inhibitor therapy?"
            ]
        },
        {
            "id": "task847-1638c7afd0b7444898525b317375cd46",
            "input": "Angiotensin II (Ang II) signaling has been implicated in cardiac arrhythmogenesis, which involves induction of reactive oxygen species (ROS). It was shown that Ang II can activate Ca/Calmodulin kinase II (CaMKII) by oxidation via a NADPH oxidase 2 (NOX2)-dependent pathway leading to increased arrhythmic afterdepolarizations. Interestingly, cAMP-dependent protein kinase A (PKA) which regulates similar targets as CaMKII has recently been shown to be redox-sensitive as well.', 'This study aims to investigate the distinct molecular mechanisms underlying Ang II-related cardiac arrhythmias with an emphasis on the individual contribution of PKA vs. CaMKII.', 'Isolated ventricular cardiac myocytes from rats and mice were used. Ang II exposure resulted in increased NOX2-dependent ROS generation assessed by expression of redox-sensitive GFP and in myocytes loaded with ROS indicator MitoSOX. Whole cell patch clamp measurements showed that Ang II significantly increased peak Ca and Na current (ICa and INa) possibly by enhancing steady-state activation of ICa and INa. These effects were absent in myocytes lacking functional NOX2 (gp91phox(-/-)). In parallel experiments using PKA inhibitor H89, the Ang II effects on peak INa and ICa were also absent. In contrast, genetic knockout of CaMKII\u03b4 (CaMKII\u03b4(-/-)) did not influence the Ang II-dependent increase in peak ICa and INa. On the other hand, Ang II enhanced INa inactivation, increased late INa and induced diastolic SR (sarcoplasmic reticulum) Ca leak (confocal Ca spark measurements) in a CaMKII\u03b4-, but not PKA-dependent manner. Surprisingly, only the increase in diastolic SR Ca leak was absent in gp91phox(-/-)myocytes suggesting that Ang II regulates INa inactivation in a manner dependent on CaMKII- but not on NOX2. Finally, we show that Ang II increased the propensity for cellular arrhythmias, for which PKA and CaMKII contribute, both dependent on NOX2.",
            "output": [
                "Does nADPH oxidase 2 mediate angiotensin II-dependent cellular arrhythmias via PKA and CaMKII?"
            ]
        },
        {
            "id": "task847-837d004d0c1e4d9b8101ba519edb9995",
            "input": "One hypothesis for thyroid cancer development is its derivation from thyroid cancer stem cells (CSCs). Such cells could arise via different paths including from mutated resident stem cells within the thyroid gland or via epithelial to mesenchymal transition (EMT) from malignant cells since EMT is known to confer stem-like characteristics. Furthermore, EMT is a critical process for epithelial tumor progression, local invasion, and metastasis formation. In addition, stemness provides cells with therapeutic resistance and is the likely cause of tumor recurrence. However, the relevance of EMT and stemness in thyroid cancer progression has not been extensively studied.', 'To examine the status of stemness in thyroid papillary cancer, we employed a murine model of thyroid papillary carcinoma and examined the expression of stemness and EMT using qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf((V600E))/TPO-Cre). This construct is only activated at the time of thyroid peroxidase (TPO) expression in differentiating thyroid cells and cannot be activated by undifferentiated stem cells, which do not express TPO.', 'There was decreased expression of thyroid-specific genes such as Tg and NIS and increased expression of stemness markers, such as Oct4, Rex1, CD15, and Sox2 in the thyroid carcinoma tissue from 6-week-old BRAF(V600E) mice indicating the dedifferentiated status of the cells and the fact that stemness was derived in this model from differentiated thyroid cells. The decreased expression of the epithelial marker E-cadherin and increased EMT regulators including Snail, Slug, and TGF-\u03b21 and TGF-\u03b23, and the mesenchymal marker vimentin demonstrated the simultaneous progression of EMT and the CSC-like phenotype. Stemness was also found in a cancer thyroid cell line (named Marca cells) derived from one of the murine tumors. In this cell line, we also found that overexpression of Snail caused up-regulation of vimentin expression and up-regulation of stemness markers Oct4, Rex1, and CD15, with enhanced migration ability of the cells. We also showed that TGF-\u03b21 was able to induce Snail and vimentin expression in the Marca cell thyroid cancer line, indicating the induction of EMT in these cells, and this induction of EMT and stemness was significantly inhibited by celastro a natural inhibitor of neoplastic cells.",
            "output": [
                "Is stemness Derived from Thyroid Cancer Cells?"
            ]
        },
        {
            "id": "task847-7a96bc9f41de49faae583d298026a13f",
            "input": "Hydrodynamic gene delivery has proved an efficient strategy for nonviral gene therapy in the murine liver but it has been less efficient in pigs. The reason for such inefficiency remains unclear. The present study used a surgical strategy to seal the whole pig liver in vivo.', 'A solution of enhanced green fluorescent protein (eGFP) DNA was injected under two different venous injection conditions (anterograde and retrograde), employing flow rates of 10 and 20\\u2009ml/s in each case, with the aim of identifying the best gene transfer conditions. The gene delivery and information decoding steps were evaluated by measuring the eGFP DNA, mRNA and protein copy number 24\\u2009h after transfection. In addition, gold nanoparticles (diameters of 4 and 15\\u2009nm) were retrogradely injected (10\\u2009ml/s) to observe, by electron microscopy, the ability of the particle to access the hepatocyte.', 'The gene delivery level was higher with anterograde injection, whereas the efficacy of gene expression was better with retrograde injection, suggesting differences in the decoding processes. Thus, retrograde injection mediates gene transcription (mRNA copy/cell) equivalent to that of intermediate expression proteins but the mRNA translation was lower than that of rare proteins. Electron microscopy showed that nanoparticles within the hepatocyte were almost exclusively 4\\u2009nm in diameter.",
            "output": [
                "Does low RNA translation activit limit the efficacy of hydrodynamic gene transfer to pig liver in vivo?"
            ]
        },
        {
            "id": "task847-a8476e8769054692a035174999c6482b",
            "input": "To explore the signal transducer and activator of transcription 3 (STAT3) signaling pathway, especially STAT3 acetylation, in angiotensin II (Ang II)-induced pro-fibrotic responses in renal tubular epithelial cells.', 'Rat renal tubular epithelial cell line (NRK-52E) was used. STAT3 acetylation and phosphorylation, as well as the expression of fibronectin, collagen IV and transforming growth factor-\u03b21 (TGF-\u03b21) were examined using Western blotting. The level and localization of STAT3 phosphorylation on Tyr705 were detected with fluorescence immunocytochemistry. The cells were transfected with a plasmid vector carrying p300 gene or siRNA targeting p300 to regulate p300 expression.', 'Overexpression of p300 significantly increased STAT3 acetylation on Lys685, STAT3 phosphorylation on Tyr705, and the expression of TGF-\u03b21, collagen IV and fibronectin in the cells. Treatment of the cells with Ang II (1 \u03bcmol/L) significantly increased STAT3 phosphorylation on Tyr705 through JAK2 activation, and dose-dependently increased the expression of fibronectin, collagen IV and TGF-\u03b21. Pretreatment with curcumin, an inhibitor of JAK2 and p300, blocked Ang II-induced effects. Knockdown of p300 significantly decreased STAT3 acetylation on Lys685, and abolished Ang II-stimulated STAT3 phosphorylation on Tyr705, whereas pretreatment of the cells with C646, a selective inhibitor of p300, inhibited Ang II-induced STAT3 nuclear translocation and the expression of TGF-\u03b21, collagen IV and fibronectin. Pretreatment of the cells with AG490, a JAK2 inhibitor, markedly inhibited Ang II-induced STAT3 phosphorylation on Tyr705 and fibronectin expression.",
            "output": [
                "Is p300-dependent STAT3 acetylation necessary for angiotensin II-induced pro-fibrotic responses in renal tubular epithelial cells?"
            ]
        },
        {
            "id": "task847-2a7e9b57a73c42f2b637300cd8686a13",
            "input": "To retrospectively review the safety and clinical efficacy of bevacizumab concomitant with chemotherapy in Chinese patients with advanced non-squamous non-small cell lung cancer (NSNSCLC).', 'Clinical data for 79 patients with NSNSCLC who received bevacizumab concomitant with chemotherapy in Chinese PLA General Hospital from April 28th 2009 to May 5th 2013 were retrospectively reviewed to analyze the clinical efficacy including disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), the Eastern Cooperative Oncology Group (ECOG) score and the safety.', 'The Eastern Cooperative Oncology Group (ECOG) score was 0-2. By the final cutoff date (June 9, 2013), 54 (68.4%) patients had disease progression and 37 (46.8%) died. The ORR was 32.9% and the DCR was 83.5%. The ORR of the first-, second-, and third- or later-line treatments were 51.4%, 25.0% and 12.5%, while the DCR were 94.3%, 80.0% and 70.8%, respectively. The median OS (mOS) and PFS (mPFS) were 13.5 and 5.83 months, respectively. The mOS of patients with the first-, second-, and third- or later-line treatments were 16.2, 10.9 and 8.30 months, while the mPFS were 7.27, 5.90 and 5.17 months, respectively. Chemotherapy-related adverse events included myelosuppression, vomiting, hepatic dysfunction and renal dysfunction, while the common serious bevacizumab-related adverse events were thromboembolic problems, gastrointestinal perforation and reversible posterior leukoencephalopathy syndrome, which could be well managed.",
            "output": [
                "Is bevacizumab concomitant with chemotherapy effective in treating Chinese patients with advanced non-squamous non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-f31ea0ef5f3b42379db6c2bd23623ba7",
            "input": "Despite the potential benefits of total quality management (TQM), many healthcare organisations encountered difficulties in its implementation. The purpose of this paper is to explore the barriers to successful implementation of TQM in healthcare organisations of Iran.', 'This study involved a mixed research design. In-depth interviews were conducted with TQM practitioners to explore TQM implementation obstacles in Iranian healthcare organisations. In addition, this study involved survey-based research on the obstacles associated with successful TQM transformation.', \"TQM implementation and its impact depend on the ability of managers to adopt and adapt its values and concepts in professional healthcare organisations. Unsuccessful TQM efforts in Iranian healthcare organisations can be attributed to the non-holistic approach adopted in its implementation, inadequate knowledge of managers' about TQM implementation, frequent top management turnover, poor planning, vague and short-termed improvement goals, lack of consistent managers' and employees' commitment to and involvement in TQM implementation, lack of a corporate quality culture, lack of team orientation, lack of continuous education and training and lack of customer focus. Human resource problems, cultural and strategic problems were the most important obstacles to TQM successful implementation, respectively.",
            "output": [
                "Does why TQM work in Iranian healthcare organisations?"
            ]
        },
        {
            "id": "task847-7178d74a2769422787c5eac618319287",
            "input": "As elegant structures designed for neural communication, synapses are the building bricks of our mental functions. Recently, many studies have pointed out that synaptic protein-associated mutations may lead to dysfunctions of social cognition. Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2 (-/-) mice to investigate their phenotypes of synaptic function and social behaviors.', 'The creation of Dlgap2 (-/-) mice was facilitated by the recombineering-based method, Cre-loxP system and serial backcross. Reversal learning in a water T-maze was used to determine repetitive behaviors. The three-chamber approach task, resident-intruder test and tube task were performed to characterize the social behaviors of mutant mice. Cortical synaptosomal fraction, Golgi-Cox staining, whole-cell patch electrophysiology and transmission electron microscopy were all applied to investigate the function and structure of synapses in the orbitofrontal cortex (OFC) of Dlgap2 (-/-) mice.', 'Dlgap2 (-/-) mice displayed exacerbated aggressive behaviors in the resident-intruder task, and elevated social dominance in the tube test. In addition, Dlgap2 (-/-) mice exhibited a clear reduction of receptors and scaffold proteins in cortical synapses. Dlgap2 (-/-) mice also demonstrated lower spine density, decreased peak amplitude of miniature excitatory postsynaptic current and ultra-structural deficits of PSD in the OFC.",
            "output": [
                "Do autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits?"
            ]
        },
        {
            "id": "task847-2791f3b822e84bfe99d27bec1c15f62c",
            "input": "Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host.', 'Intra-host variants of the HCV E1/E2 region were extensively sampled from 58 chronically infected patients. After NGS error correction, the average number of reads and variants obtained from each sample were 3202 and 464, respectively. The distance between each pair of variants was calculated and networks were created for each patient, where each node is a variant and two nodes are connected by a link if the nucleotide distance between them is 1. The work focused on large components having > 5% of all reads, which in average account for 93.7% of all reads found in a patient.",
            "output": [
                "Does next-generation sequencing reveal large connected networks of intra-host HCV variants?"
            ]
        },
        {
            "id": "task847-5304fb57fde94db7976b9c15366fe4d7",
            "input": "The role of signal transducer and activator of transcription 3 (Stat3) in liver fibrosis is still controversial. Since hepatic stellate cells (HSCs) and transforming growth factor-\u03b21 (TGF-\u03b21) are central to the fibrogenesis, our goal was to clarify the mechanism of Stat3 crosslinking of TGF-\u03b21 signaling.', 'Stat3, TGF-\u03b21 mRNA and protein expressions were examined in liver tissues of chronic hepatitis B (CHB) patients and diethylinitrosamine (DEN)-induced rat fibrosis model. The effect of Stat3 activation or suppression on TGF-\u03b21 signaling in HSCs was tested in vitro and in vivo.', 'Stat3 expression as well as TGF-\u03b21 was increased in CHB patients and DEN-induced fibrosis rat model. This was strongly correlated with increase in fibrosis staging. TGF-\u03b21, a mediator of fibrosis, was enhanced by Stat3, but suppressed by siRNA-mediated RNA knockdown of Stat3 (siStat3) or Janus kinase 2 inhibitor (AG490) both in vivo and in vitro. Stat3 crosslinking TGF-\u03b21 signaling plays an important role in HSC activation and increasing fibrosis related products. TGF-\u03b21 could not achieve profibrogenic cytokine and anti-apoptosis characteristics without Stat3 activation in HSCs.",
            "output": [
                "Does stat3 signaling activation crosslinking of TGF-\u03b21 in hepatic stellate cell exacerbate liver injury and fibrosis?"
            ]
        },
        {
            "id": "task847-22c270e6e99c46f39d9e69478893051e",
            "input": "Eotaxin proteins are a potential therapeutic target in treating the peribronchial eosinophilia associated with allergic airway diseases. Since inflammation is often associated with an increased generation of reactive oxygen species (ROS), oxidative stress is a mechanistically imperative factor in asthma. Astragalin (kaempferol-3-O-glucoside) is a flavonoid with anti-inflammatory activity and newly found in persimmon leaves and green tea seeds. This study elucidated that astragalin inhibited endotoxin-induced oxidative stress leading to eosinophilia and epithelial apoptosis in airways.', 'Airway epithelial BEAS-2B cells were exposed to lipopolysaccharide (LPS) in the absence and presence of 1-20 \u03bcM astragalin. Western blot and immunocytochemical analyses were conducted to determine induction of target proteins. Cell and nuclear staining was also performed for ROS production and epithelial apoptosis.', 'When airway epithelial cells were exposed to 2 \u03bcg/ml LPS, astragalin nontoxic at \u2264 20 \u03bcM suppressed cellular induction of Toll-like receptor 4 (TLR4) and ROS production enhanced by LPS. Both LPS and H2O2 induced epithelial eotaxin-1 expression, which was blocked by astragalin. LPS activated and induced PLC\u03b31, PKC\u03b22, and NADPH oxidase subunits of p22phox and p47phox in epithelial cells and such activation and induction were demoted by astragalin or TLR4 inhibition antagonizing eotaxin-1 induction. H2O2-upregulated phosphorylation of JNK and p38 MAPK was dampened by adding astragalin to epithelial cells, while this compound enhanced epithelial activation of Akt and ERK. H2O2 and LPS promoted epithelial apoptosis concomitant with nuclear condensation or caspase-3 activation, which was blunted by astragalin.",
            "output": [
                "Does astragalin inhibit airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling?"
            ]
        },
        {
            "id": "task847-ed6d6d70174145658b9865f05184d191",
            "input": "A cross-sectional study in a general health examination.', 'To investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and lumbar disk herniation (LDH).', 'Lumbar disk herniation (LDH) is a major cause of low back pain and sciatica. Various vascular risk factors such as obesity, diabetes mellitus, and smoking have been reported to be associated with LDH. BaPWV is an early indicator of subclinical atherosclerosis.', 'A total of 490 participants with LDH and 490 participants without LDH were selected for the evaluation of baPWV. BaPWV was measured using an automatic device. The prevalence of LDH was calculated by the quartiles of baPWV levels. Multiple linear regression analysis was performed to evaluate the risk factors for baPWV.', 'LDH patients had significantly higher readings of baPWV compared with non-LDH subjects (P<0.001). The prevalence rate of LDH gradually increased according to baPWV quartiles. In addition, the levels of baPWV tended to increase as the frequency of physical activity reduced. Multiple linear regression analysis showed that body mass index, low-density lipoprotein cholesterol, physical activity, and systolic blood pressure contributed to increased baPWV.",
            "output": [
                "Is physical activity associated with elevated arterial stiffness in patients with lumbar disk herniation?"
            ]
        },
        {
            "id": "task847-e9090fb9a9034b97913ee262104ad427",
            "input": "To investigate changes in autoreactive T-cell responses against PMP-22 and P2 antigen as well as a T-cell memory repertoire in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) induced by repeated intravenous immunoglobulin (IVIg) treatment.', 'In an observational trial, we prepared cryopreserved human peripheral blood monocytes from blood from 34 patients with CIDP (18 treatment na\u00efve and 16 maintenance IVIg treatment) and from 14 healthy controls (non-immune neuropathy and healthy control). Treatment response was defined by clinical evaluation. The autoantigen-specific T-cell response was analysed by enzyme linked immunosorbent spot (ELISPOT) assay before IVIg start (baseline) and at follow-up. The T-cell memory subsets were analysed by using flow cytometric analysis.', 'Myelin-derived P2-specific and PMP-22-specific IFN-\u03b3 producers were increased in IVIg responders compared with non-responders before treatment, which decreased by repeated IVIg infusion cycles. Treatment responders but not non-responders showed higher frequencies of CD4 T effector memory (TEM) and T central memory frequencies at baseline compared with maintenance IVIg treatment patients and controls. In addition, IVIg treatment was associated with a significant reduction in CD8 TEM at follow-up.",
            "output": [
                "Does effective treatment with intravenous immunoglobulins reduce autoreactive T-cell response in patients with CIDP?"
            ]
        },
        {
            "id": "task847-30e636c4110c4018ad864770b5ea2e09",
            "input": "The purpose of the present study was to investigate the effects of self-controlled feedback on the learning of a sequential-timing motor task in introverts and extroverts.', 'Fifty-six university students were selected by the Eysenck Personality Questionnaire. They practiced a motor task consisting of pressing computer keyboard keys in a specific spatial and temporal pattern. The experiment consisted of practice, retention, and transfer phases. The participants were distributed into 4 groups, formed by the combination of personality trait (extraversion/introversion) and type of feedback frequency (self-controlled/yoked).', 'The results showed superior learning for the groups that practiced in a self-controlled schedule, in relation to groups who practiced in an externally controlled schedule, F(1, 52) = 4.13, p < .05, eta2 = .07, regardless of personality trait.",
            "output": [
                "Does self-controlled practice enhance motor learning in introverts and extroverts?"
            ]
        },
        {
            "id": "task847-453d9825baef4647a454bcecdae58afb",
            "input": "Left atrial pressure and its surrogate, pulmonary capillary wedge pressure (PCWP), are important for determining diastolic function. The role of transthoracic echocardiography (TTE) in assessing diastolic function is well established in awake subjects. The objective was to assess the accuracy of predicting PCWP by TTE and transesophageal echocardiography (TEE) during coronary artery surgery.', 'In 27 adult patients undergoing on-pump coronary artery surgery, simultaneous echocardiographic and hemodynamic measurements were obtained immediately before anesthesia (TTE), after anesthesia and mechanical ventilation (TTE and TEE), during conduit harvest (TEE), and after separation from cardiopulmonary bypass (TEE).', \"Twenty patients had an ejection fraction (EF) of 0.5 or greater. With the exception of E/e' and S/D ratios, echocardiographic values changed over the echocardiographic studies. In patients with low EF, E velocity, deceleration time, pulmonary vein D, S/D, and E/e' ratios correlated well with PCWP before anesthesia. After induction of anesthesia using TTE or TEE, correlations were poor. In normal EF patients, correlations were poor for both TEE and TTE at all five stages. The sensitivity and specificity of echocardiographic values were not high enough to predict raised PCWP except for a fixed curve pattern of interatrial septum (area under the curve 0.89 for PCWP \u2265 17, and 0.98 for \u2265 18 mmHg) and S/D less than 1 (area under the curve 0.74 for PCWP \u2265 17, and 0.78 for \u2265 18 mmHg).",
            "output": [
                "Does interatrial septum motion but not Doppler assessment predict elevated pulmonary capillary wedge pressure in patients undergoing cardiac surgery?"
            ]
        },
        {
            "id": "task847-a063fef66a7c4be19d75bf03de9858da",
            "input": "The precise pathogenesis of chronic spontaneous urticaria (CSU) remains unknown. However, an important association between CSU and autoimmune disorders such as Hashimoto's disease (HD) has been reported. We investigated the frequency of HD as a comorbidity of CSU and the prevalence rate of autoreactivity among CSU patients with HD.\", 'The presence of thyroid autoantibodies and the levels of thyroid hormones were examined in 40 CSU patients who showed urticaria symptoms for >4 weeks. Patients who were diagnosed with HD, including subclinical ones, and were in need of treatment received thyroid therapy, and the changes in their urticarial symptoms were observed. An autologous serum skin test (ASST) was also performed to examine the relation of CSU with autoreactivity.', 'Eleven of the 40 CSU patients were diagnosed with HD, and 4 of the 5 patients who received and completed thyroid therapy showed considerable remission of urticarial symptoms during and after treatment. In addition, the rate of positive ASST results tended to be higher in CSU patients with HD (5 of 7) than in those without HD (2 of 6).",
            "output": [
                "Is hashimoto 's disease a frequent comorbidity and an exacerbating factor of chronic spontaneous urticaria?"
            ]
        },
        {
            "id": "task847-c749b794781a4516b20dcd7112f6e9c2",
            "input": "Various types of periacetabular osteotomies have been proposed to treat acetabular dysplasia for young and active patients. Acetabular dysplasia is prevalent in women and rare in men, therefore few reports exist concerning periacetabular osteotomy of male patients. The purpose of this study is to clarify the gender differences in surgical techniques, radiographic and clinical outcomes.', 'Between 1989 and 2007, we performed 530 eccentric rotational acetabular osteotomies and followed them annually for more than five years. Thirty-six male patients were investigated. As a control group, 72 female patients were matched for age and preoperative stage of osteoarthritis at the time of surgery. We evaluated operative time and blood loss, radiographic parameters, Harris Hip Score (HHS) and survival rate. We investigated the clinical and radiographic differences between men and women.', 'The mean operative time was 148 min in males and 135 min in females. The bleeding during surgery was 445 g in males and 351 g in females. HHS improved 94.1 points in males and 93.5 points in women postoperatively. The mean CE angle improved 31.7\u00b0 in males and 35.1\u00b0 in females. The mean AHI was 90.8% in males and 94.1% in females postoperatively. The survival rate of male patients were 92.8% and that of female patients were 98.1%.",
            "output": [
                "Does gender difference affect the outcomes of eccentric rotational acetabular osteotomy used in hip dysplasia?"
            ]
        },
        {
            "id": "task847-f39f5111bcdb433482d6b3dbfba5c125",
            "input": "Known factors affecting the management of vesicoureteral reflux (VUR) include reflux grade, infection frequency, age and gender. We hypothesized that provider preference is highly associated with management.', 'Utilizing the national billing database, Faculty Practice Solutions Center, a multivariable logistic regression model, was applied to analyze the association of pediatric urologist treatment patterns, patient age, gender, uni- or bilateral disease, insurance type, presence of nephropathy and race with the type of VUR treatment a patient would receive.', \"We identified 59 pediatric urologists who managed 7,882 new reflux patients from 2009 to 2011. Over this 3-year period there was wide variation in surgical utilization between surgeons (mean 50 %) but minimal change for each surgeon (5 %). For every 100 new reflux patients, median utilization of reimplantation surgery and injection of dextranomer/hyaluronic acid copolymer (Deflux) was 26 and 20 %, respectively. Age ranked highest in predicting surgical versus non-surgical management, while a surgeon's historic Deflux utilization rate ranked highest in predicting surgery type. Older age, female gender and white race also increased the odds of Deflux utilization over reimplantation.",
            "output": [
                "Is physician preference a major factor in management of vesicoureteral reflux?"
            ]
        },
        {
            "id": "task847-93304fdde9c842eaafea31d268834f01",
            "input": "Filaggrin (FLG) is a major protein component of the stratum corneum (SC) layer, and FLG loss-of-function mutations are a predisposing factor for atopic dermatitis (AD). Previous cohort studies of children from northern and western Europe have reported FLG loss-of-function mutation frequencies of 15.1-20.9% and 5.8-13.0% in AD and non-AD groups, respectively.', 'To elucidate the association between AD prevalence of FLG loss-of-function mutation carriers and climate conditions, we determined the AD prevalence and FLG loss-of-function mutation frequencies in a cohort of children from Ishigaki Island. Ishigaki Island has a subtropical climate with high humidity (monthly average, 60.8-78.7%) and high temperature (monthly average, 18.5-29.4\u00b0C) throughout the year.', 'We diagnosed AD prevalence and analyzed eight FLG loss-of-function mutations in the Japanese population against a cohort of 721 children from the Kyushu University Ishigaki Atopic Dermatitis Study (KIDS) cohort. Parents gave consent for the mutation analysis during their medical examinations from 2001 to 2006.', 'Average AD prevalence was 7.3% per year, and a total of 127 children (17.6%) were diagnosed with AD at least once between 2001 and 2006. The average total serum IgE level differed significantly between the AD and non-AD groups (199.0 and 69.0IU/ml, respectively). Although five kinds of FLG loss-of-function mutations isolated in previous Japanese FLG mutation studies were identified, the FLG loss-of-function mutation frequency in children of the KIDS cohort was not significantly different between the AD and non-AD groups (7.9% and 6.1%, respectively; P=0.174).",
            "output": [
                "Are filaggrin loss-of-function mutations a predisposing factor for atopic dermatitis in an Ishigaki Island under subtropical climate?"
            ]
        },
        {
            "id": "task847-440067231a74419484d927f8ed0733ef",
            "input": "Our study reexamines the prevalence of interval colorectal cancer (I-CRC) by manually reviewing CRC cases at a single institution.', 'In 2% to 8% of patients with CRC, diagnosis occurs during the interval 6 to 36 months after a cancer-free colonoscopy. Rates are often determined by linking the date of colonoscopy with cancer registry information.', 'We examined all colonoscopies from 1993 to 2011. These examinations were linked with Pennsylvania Cancer Registry data. Matched charts were manually reviewed. We determined whether the CRC was \"prevalent\" or, for patients with a previous colonoscopy, whether they were interval or noninterval based on time from last colonoscopy. For interval cases, we identified \"administrative errors\" that could falsely increase the number of reported I-CRC.', 'Over the study period, 43,661 colonoscopies were performed, with 1147 (2.6%) positive for CRC after excluding cases (n=52) in which patients had IBD, previous surgery, or nonadenocarcinoma malignancy. Prevalent CRCs totaled 1062 (92.6%). Noninterval CRCs (diagnosed over 36 mo from index colonoscopy) were present in 40 (3.5%). There remained 45 (3.9%) potential I-CRC cases. However, after manual review, 21 cases were found to be administrative errors. Therefore, the accurate proportion of colonoscopies that found an I-CRC was 2.1% (95% confidence interval, 1.5%-3.2%).",
            "output": [
                "Does administrative Database Research overestimate the Rate of Interval Colon Cancer?"
            ]
        },
        {
            "id": "task847-3fdb652b0af646b7a62399be9e51b381",
            "input": "Innate immune protein C1q plays a dual role in the chronic inflammatory disease of atherosclerosis. Complement activation via C1q exacerbates pathology in the atherosclerotic lesion in later stages of the disease. However, in early stages of disease C1q is protective. We hypothesize that complement-independent activities of C1q are involved in reprogramming macrophage inflammatory polarization.', 'The influence of C1q on macrophage inflammatory responses during clearance of oxLDL was examined. Changes in cytokines at the gene and protein level were measured by quantitative PCR and ELISA assay.', 'C1q modulated cytokine expression in Raw264.7 macrophages during ingestion of oxLDL. Levels of pro-inflammatory cytokines IL-1\u03b2 and IL-6 were downregulated by C1q, whereas levels of the anti-inflammatory cytokine IL-10 were increased. In addition, data from an NF\u03baB-luciferase gene reporter assay suggest that C1q suppresses activation of NF\u03baB during lipoprotein clearance in macrophages, providing one mechanism by which C1q downregulates pro-inflammatory cytokine production.",
            "output": [
                "Does complement protein C1q promote macrophage anti-inflammatory M2-like polarization during the clearance of atherogenic lipoproteins?"
            ]
        },
        {
            "id": "task847-6d7253e362114e90a6ae7733e105e163",
            "input": "The reconstruction of large facial bony defects using microvascular transplants requires extensive surgery to achieve full rehabilitation of form and function. The purpose of this study is to measure the agreement between virtual plans and the actual results of maxillofacial reconstruction.', 'This retrospective cohort study included 30 subjects receiving maxillofacial reconstruction with a preoperative virtual planning. Parameters including defect size, position, angle and volume of the transplanted segments were compared between the virtual plan and the real outcome using paired t test.', 'A total of 63 bone segments were transplanted. The mean differences between the virtual planning and the postoperative situation were for the defect sizes 1.17 mm (95 % confidence interval (CI) (-.21 to 2.56 mm); p\\u2009=\\u20090.094), for the resection planes 1.69 mm (95 % CI (1.26-2.11); p\\u2009=\\u20090.033) and 10.16\u00b0 (95 % CI (8.36\u00b0-11.96\u00b0); p\\u2009<\\u20090.001) and for the planes of the donor segments 10.81\u00b0 (95 % CI (9.44\u00b0-12.17\u00b0); p\\u2009<\\u20090.001) The orientation of the segments differed by 6.68\u00b0 (95 % CI (5.7\u00b0-7.66\u00b0); p\\u2009<\\u20090.001) from the virtual plan; the length of the segments differed by -0.12 mm (95 % CI (0.89-0.65 mm); not significant (n.s.)), respectively, while the volume differed by 73.3 % (95 % CI (69.4-77.6 %); p\\u2009<\\u20090.001). The distance between the transplanted segments and the remaining bone was 1.49 mm (95 % CI (1.24-1.74); p\\u2009<\\u20090.001) and between the segments 1.49 mm (95 % CI (1.16-1.81); p\\u2009<\\u20090.001).",
            "output": [
                "Does virtual planning of complex head and neck reconstruction result in satisfactory match between real outcomes and virtual models?"
            ]
        },
        {
            "id": "task847-753c6e9c53ae44b49735bea816717e5c",
            "input": "Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect.', 'We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n\\xa0= 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n\\xa0= 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods.', 'There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P\\xa0= .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P\\xa0= .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P\\xa0= .003) and the accelerated dosing regimen (P\\xa0= .03).",
            "output": [
                "Does an accelerated infliximab induction regimen reduce the need for early colectomy in patients with acute severe ulcerative colitis?"
            ]
        },
        {
            "id": "task847-a9d9c7f3b04e4db5804712d8a9c3f6e7",
            "input": "Dehydroepiandrosterone (DHEA) was shown to improve the immune function and survival in experimental sepsis. This study examined the effect of DHEA on intestinal leukocyte recruitment during experimental sepsis, considering factors of gender (male, female and ovariectomized female animals) and combined treatment using orthovanadate (OV) in two models of sepsis.', 'Male rats underwent colon ascendens stent peritonitis (CASP) or endotoxemia. DHEA was administered after induction of experimental sepsis. Changes in leukocyte adherence and capillary perfusion (measured as intestinal functional capillary density - FCD) were assessed using intravital microscopy. While DHEA increased baseline leukocyte adherence in control animals, DHEA reduced leukocyte adherence and increased FCD in male animals with CASP. These effects were also observed in DHEA-treated ovariectomized female rats with CASP. Similarly, the administration of DHEA reduced the number of adherent leukocytes to intestinal venules by 30% in the endotoxemia model. The combined treatment of DHEA and OV significantly reduced adherence of leukocytes to intestinal venules and improved FCD.",
            "output": [
                "Does combination of dehydroepiandrosterone and orthovanadate administration reduce intestinal leukocyte recruitment in models of experimental sepsis?"
            ]
        },
        {
            "id": "task847-c078de5680a94883a4c0b55319ef260f",
            "input": "In many areas of orthopaedics, patients with greater levels of psychological distress report inferior self-assessments of pain and function. This effect can lead to lower-than-expected baseline scores on common patient-reported outcome scales, even those not traditionally considered to have a psychological component.', 'This study attempts to answer the following questions: (1) Are higher levels of psychological distress associated with clinically important differences in baseline scores on the VAS for pain, the Simple Shoulder Test, and the American Shoulder and Elbow Surgeons score in patients undergoing arthroscopic rotator cuff repair? (2) Does psychological distress remain a negative predictor of baseline shoulder scores when other clinical variables are controlled?', 'Eighty-five patients with full-thickness rotator cuff tears were prospectively enrolled. Psychological distress was quantified using the Distress Risk Assessment Method questionnaire. Patients completed baseline self-assessments including the VAS for pain, the Simple Shoulder Test, and the American Shoulder and Elbow Surgeons score. Age, sex, BMI, smoking status, American Society of Anesthesiologists classification, tear size, and tear retraction were recorded for each patient. Bivariate correlations and multivariate regression models were used to assess the effect of psychological distress on patient self-assessment of shoulder pain and function.', 'Distressed patients reported higher baseline VAS scores (6.7 [95% CI, 4.4-9.0] versus 2.9 [95% CI, 2.3-3.6], p\\xa0=\\xa00.001) and lower baseline Simple Shoulder Test (3.7 [95% CI, 2.9-4.5] versus 5.7 [95% CI 5.0-6.4], p\\xa0=\\xa00.001) and American Shoulder and Elbow Surgeons scores (39 [95% CI, 34-45] versus 58 [95% CI, 53-63], p\\xa0<\\xa00.001). Distress remained associated with higher VAS scores (p\\xa0=\\xa00.001) and lower Simple Shoulder Test (p\\xa0<\\xa00.001) and American Shoulder and Elbow Surgeons scores (p\\xa0<\\xa00.001) when age, sex, BMI, American Society of Anesthesiologists classification, smoking status, tear size, and tear retraction were controlled.",
            "output": [
                "Does psychological distress negatively affect self-assessment of shoulder function in patients with rotator cuff tears?"
            ]
        },
        {
            "id": "task847-459ca1761e5444ba807fb185c06a491a",
            "input": "Plants, fungal endophytes (FEs) and the changing environment interact with each other forming an interlaced network. This study evaluates nonadditive and interactive effects of the FE Acremonium strictum and drought treatment on Atractylodes lancea plantlets.', \"By applying FEs (meristem cultures of At. lancea, fungal inoculation of Ac. strictum and plantlet acclimatization) and drought treatment (regular watering, mild drought, severe drought), a research system of At. lancea ramets under different treatments was established. During 12 days of drought treatment, the plantlets' physiological responses and basic growth traits were measured and analysed. Although drought and FE presence affected plantlet traits to differing degrees, the interactive effects of the two were more pronounced. In particular under mild drought treatment, the FE conferred drought tolerance to plantlets by enhancing leaf soluble sugars, proteins, proline and antioxidant enzyme activity; decreasing the degree of plasmalemma oxidation; and increasing the host's abscisic acid level and root:shoot ratio. When exposed to regular watering or severe drought, these effects were not significant.",
            "output": [
                "Does drought degree constrain the beneficial effects of a fungal endophyte on Atractylodes lancea?"
            ]
        },
        {
            "id": "task847-bfee15a7fdb84d1c8b910afc9184cc9a",
            "input": "H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.', 'We report the application of EHMT1 and EHMT2 specific chemical inhibitors to sensitize CML cell lines to interferon and imatinib treatments. Inhibition of EHMT1 and EHMT2 with BIX01294 enhances the cytotoxicity of IFN\u03b12a in four CML cell lines, K562, KCL22, BV173 and KT1 cells. Chromatin immunoprecipitation assay shows that BIX01294 treatment enhances type I interferon response by reducing H3K9me2 at the promoters of interferon-stimulated genes. Additionally, BIX01294 treatment augments IFN\u03b12a- and imatinib-mediated apoptosis in CML cell lines. Moreover, our data suggest that the expression level of EHMT1 and EHMT2 inversely correlates with the type I interferon responsiveness in CML cell lines.",
            "output": [
                "Does inhibition of euchromatic histone methyltransferase 1 and 2 sensitize chronic myeloid leukemia cells to interferon treatment?"
            ]
        },
        {
            "id": "task847-fb3f4c0f02f34cacb17ee3bb72940b95",
            "input": "Computed tomography (CT) substitute images can be generated from ultrashort echo time (UTE) MRI sequences with radial k-space sampling. These CT substitutes can be used as ordinary CT images for PET attenuation correction and radiotherapy dose calculations. Parallel imaging allows faster acquisition of magnetic resonance (MR) images by exploiting differences in receiver coil element sensitivities. This study investigates whether non-Cartesian parallel imaging reconstruction can be used to improve CT substitutes generated from shorter examination times.', 'The authors used gridding as well as two non-Cartesian parallel imaging reconstruction methods, SPIRiT and CG-SENSE, to reconstruct radial UTE and gradient echo (GE) data into images of the head for 23 patients. For each patient, images were reconstructed from the full dataset and from a number of subsampled datasets. The subsampled datasets simulated shorter acquisition times by containing fewer radial k-space spokes (1000, 2000, 3000, 5000, and 10,000 spokes) than the full dataset (30,000 spokes). For each combination of patient, reconstruction method, and number of spokes, the reconstructed UTE and GE images were used to generate a CT substitute. Each CT substitute image was compared to a real CT image of the same patient.', 'The mean absolute deviation between the CT number in CT substitute and CT decreased when using SPIRiT as compared to gridding reconstruction. However, the reduction was small and the CT substitute algorithm was insensitive to moderate subsampling (\u2265 5000 spokes) regardless of reconstruction method. For more severe subsampling (\u2264 3000 spokes), corresponding to acquisition times less than a minute long, the CT substitute quality was deteriorated for all reconstruction methods but SPIRiT gave a reduction in the mean absolute deviation of down to 25 Hounsfield units compared to gridding.",
            "output": [
                "Does cT substitute derived from MR images reconstructed with parallel imaging?"
            ]
        },
        {
            "id": "task847-7f7d2cbeeaa04d49a1a2fbe6e5236066",
            "input": "The aim of this study is to examine the hypothesis that prolonged rupture of membranes (PROM) is associated with increased cord blood erythropoietin (EPO) concentrations, proportional to the duration of ruptured membranes.', 'This study is a prospective, cross-sectional, observational (noninterventional) cohort study of mother-infant pairs. Criteria for inclusion were as follows: active labor with or without ruptured membranes and vaginally delivered neonates. Excluded were infants with major factors known to be associated with a potential increase in fetal erythropoiesis.', 'A total of 40 mother-infant pairs were recruited. EPO was not influenced by duration of ruptured membranes and significantly correlated only with maternal body mass index.",
            "output": [
                "Does increased nucleated red blood cells count in prolonged rupture of membranes is not erythropoietin driven?"
            ]
        },
        {
            "id": "task847-df587b52f3e94bbf9342115fadd795ea",
            "input": "To confirm that the severity of inflammation can promote the colitis-associated colorectal cancer(CAC) and explore the function of STAT3 signal pathway in CAC.', 'Mutagenic agent azoxymethane(AOM) and pro-inflammatory agent dextran sodium sulfate salt (DSS) were used to develop a mouse model of CAC. By changing the concentration of DSS (0, 1% and 2% respectively), the mouse model with different extent of severity of inflammation was developed and the risk of carcinogenesis among these groups was compared. The expression of STAT3 signal pathway was detected by immunohistochemistry staining.', 'In the evaluation of inflammatory severity, disease activity index, histopathological inflammation scores and the expression of pro-inflammation chemokines such as TNF-\u03b1, IL-6 and IL-12 in the higher inflammatory response group were higher than that in the lower inflammatory response group. The incidence of colorectal tumor was 100%(12/12) in the higher inflammatory response group and the incidence of colorectal tumor was 58.3%(7/12) in the lower inflammatory response group, and the difference between these two group was statistically significant (P<0.05). The multiplicity(number of tumors/colon) was 12.5\u00b10.5 in the higher inflammatory response group and the multiplicity was 6.6\u00b11.0 in the lower inflammatory response group, and the difference between these two groups was statistically significant (P<0.001). The tumor load(sum of tumor diameters per mouse) in the higher inflammatory response group was 44.2\u00b12.4 mm and that in the lower inflammatory response group was only 18.7\u00b12.7 mm, and the difference between these two groups was statistically significant (P<0.0001). Moreover, the expression of p-STAT3 (Tyr705) was higher in colitis tissue of the higher inflammatory response group than that of the lower inflammatory response group.",
            "output": [
                "Does [ Inflammation promote the development of colitis-associated colorectal cancer ]?"
            ]
        },
        {
            "id": "task847-fce25c8483124cdd9cb69ba06987ea18",
            "input": "High fructose intake has been suggested to be a key factor that induces nonalcoholic fatty liver disease (NAFLD), but the evidence from large epidemiologic studies is lacking.', 'We examined the cross-sectional association between fructose intake and NAFLD by using the Fatty Liver Index (FLI) and the NAFLD liver fat score.', 'The Helsinki Birth Cohort Study investigated 2003 Finnish men and women born in 1943-1944 in Helsinki who participated in a clinical health examination in the years 2001-2004. Trained study nurses measured weight, height, and waist circumference, and body mass index was calculated. Laboratory staff drew fasting blood for measurements of triglycerides and \u03b3-glutamyl-transferase. The FLI and the NAFLD liver fat score were calculated on the basis of these measurements. Habitual fructose and other dietary intake over the past year were assessed by using validated and standardized 131-item food-frequency questionnaires. Data were analyzed in a cross-sectional manner by using logistic regression modeling with statistical software.', 'In a model adjusted for age, sex, and energy intake, participants in the highest fructose intake quartile (range: 29.2-88.0 g/d) had lower risk of NAFLD assessed by using the FLI (OR: 0.56; 95% CI: 0.42, 0.75; P-trend < 0.001) and NAFLD liver fat score (OR: 0.72; 95% CI: 0.53, 0.99; P-trend < 0.001) than that of the lowest intake quartile (range: 2.2-15.2 g/d). This association remained after adjustment for educational attainment, smoking, physical activity, and other dietary variables only for the FLI (OR: 0.68; 95% CI: 0.47, 0.84; P-trend < 0.05).",
            "output": [
                "Is higher fructose intake inversely associated with risk of nonalcoholic fatty liver disease in older Finnish adults?"
            ]
        },
        {
            "id": "task847-4668f29b18294aed8d87c4429047ad79",
            "input": "Diabetic retinopathy is a common diabetic eye disease caused by changes in retinal ganglion cells (RGCs). Several studies suggest that the oxidative stress plays a role in the pathogenesis of diabetic retinopathy in adults. Formononetin is a flavone with powerful antioxidant properties that exists naturally in various plants and Chinese medicine. In the present study, an attempt has been made to investigate the antioxidative effects of formononetin on H2O2-induced apoptosis of RGC-5 cells.', 'Exposure of retinal ganglion cells (RGCs) to the indicated concentrations of formononetin and H2O2 for 24 h, analyzed by MTT assay. Cells were stained with Annexin V-FITC and PI, analyzed by flow cytometry. And the level of superoxide anions, malondialdehyde (MDA, a marker of lipid peroxidation), 8-hydroxy-2-deoxyguanosine (8-OHdG, indicator of oxidative DNA damage) and MnSOD (manganese superoxide dismutase) activity were measured by kits.', 'Formononetin reduced hydrogen peroxide (H2O2)-induced apoptosis and improved the levels or activity of indicators of oxidative stress. Formononetin also inhibited the activation of nuclear factor-kappaB (NF-\u03baB), which is a significant transcription factor for RGC-5 apoptosis.",
            "output": [
                "Does formononetin attenuate hydrogen peroxide ( H2O2 ) -induced apoptosis and NF-\u03baB activation in RGC-5 cells?"
            ]
        },
        {
            "id": "task847-d630684e6a654e058d3363ab00837b41",
            "input": "Zuo-Jin-Wan (ZJW), a traditional Chinese medicine formula, has been identified to be effective against drug resistance in cancer. In the present study, we investigated the effect of ZJW on acquired oxaliplatin-resistant and the PI3K/Akt/NF-\u03baB pathway in vitro.', 'We tested the dose-response relationship of ZJW on reversing drug-resistance by CCK-8 assay and flow cytometry analysis in vitro. The protein expression of P-gp, MRP-2, LRP, and ABCB1 mRNA expression level were evaluated by Western blot and quantitative RT-PCR. The activities of PI3K/Akt/NF-\u03baB pathway were also examined with or without ZJW, including Akt, I\u03baB, p65 and their phosphorylation expression.', 'We found that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs and increased oxaliplatin (L-OHP)-induced cell apoptosis in a time- and dose-dependent manner. Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-\u03baB, which is necessary in the activation of the PI3K/Akt/NF-\u03baB pathway. The effect of ZJW in reversing drug-resistance and suppressing phosphorylation of Akt (Ser473) and NF-\u03baB were weakened after treatment with a PI3K/Akt activator in HCT116/L-OHP cells.",
            "output": [
                "Does zuo Jin Wan reverse P-gp-mediated drug-resistance by inhibiting activation of the PI3K/Akt/NF-\u03baB pathway?"
            ]
        },
        {
            "id": "task847-67ee0b7216eb4147a02824dfa8174358",
            "input": "To determine if patients with pathological, medical renal disease, defined as evidence of pathological abnormalities indicative of renal damage in the non-neoplastic partial nephrectomy specimens, have worsened functional outcomes following robot-assisted partial nephrectomy.', 'Sixty patients with and 101 without pathologically proven renal disease on non-neoplastic renal specimens were evaluated for differences in postoperative outcomes following robot-assisted partial nephrectomy. Multiple linear regression modeling assessed for factors influencing early and late declines in renal function.', 'The two groups were similar in all preoperative parameters. Both patients with and without pathological renal disease had similar lengths of hospitalization, transfusions, and complication rates. The percent change in glomerular filtration rate was similar for patients with and without pathological renal disease (-8.8% vs. -12.2%, p=0.194). Patients with pathological renal disease had less chronic kidney disease upstaging than patients without renal disease (18.3% vs. 39.6%, p=0.006). Increasing age (p=0.030) and higher preoperative glomerular filtration rates (p=0.044) predicted worse late percentage declines in renal function, while increased warm ischemia time predicted late chronic kidney disease upstaging (p=0.043).",
            "output": [
                "Do patients with Pathologically Proven Renal Disease Have Similar Declines in Renal Function Following Robot-Assisted Partial Nephrectomy?"
            ]
        },
        {
            "id": "task847-da7b927c106543d6b4ad0fa42c99a590",
            "input": "We performed diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) studies in a group of patients with subacute sclerosing panencephalitis (SSPE) in order to estimate the pathologic process underlying the phenotypic variability.', 'Patients with SSPE who had MRI including DTI and MRS examinations were evaluated according to their clinical status as determined by the SSPE Scoring System and their mental age as determined by tests appropriate for age and developmental level. Comparisons of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and metabolite ratios of frontal periventricular white matter, parieto-occipital periventricular white matter, and globus pallidus in both hemispheres were made between control and SSPE groups, and between SSPE subgroups.', 'Control (n = 18) and SSPE (n = 39) groups differed in all DTI and MRS parameters except FA, choline (Cho), and Cho/creatine (Cr). SSPE cases had higher ADC and lower N-acetylaspartate (NAA), NAA/Cho, and NAA/Cr in all regions of interest, suggesting cell loss. Disease progression rate and neurologic deficit appeared to be associated with the degree of ADC elevation and NAA reduction: the group with severe global deterioration had the lowest NAA (230.75 \u00b1 197.97 in forceps minor), and rapid progression was associated with acute reduction in NAA.",
            "output": [
                "Is neuronal loss an early component of subacute sclerosing panencephalitis?"
            ]
        },
        {
            "id": "task847-9e58c5d00f504a6d93a6bf1cb73bdc67",
            "input": "Coronary artery calcification (CAC) is a prominent feature of atherosclerosis and is associated with cardiovascular events. In vitro studies have suggested that osteoprotegerin (OPG) and osteocalcin (OC) exert anticalcification potential in the vessel wall. The objective of this study was to investigate the association of CAC and serum bone biomarkers in persons with type 2 diabetes.', 'We examined 50 individuals with type 2 diabetes. CAC imaging was performed by multidetector computed tomography. CAC scores \u226510, expressed in Agatston units, were considered abnormal. OC, undercarboxylated OC (ucOC), and OPG levels were determined by enzyme-linked immunosorbent assay.', 'Abnormal CAC scores were found for 64% of the study cohort. OPG levels were significantly elevated (5.5 \u00b1 2.0 pmol/L vs. 4.2 \u00b1 1.7 pmol/L; P = .026) for those with abnormal CAC scores. No univariate differences were found for OC or ucOC. Logistic regression analyses revealed that an increase in serum OPG level was significantly associated with an increase in CAC score (odds ratio, 3.324; 95% confidence interval, 1.321 to 8.359; P = .011). Longer duration of diabetes was a significant covariate (P = .026), whereas nonsignificant covariates in the final model were age, gender, systolic blood pressure, body mass index, insulin resistance determined by the homeostasis model assessment for insulin resistance, leptin, adiponectin, and glycemic control. The Nagelkerke R2 for the model was 0.66. Neither OC nor ucOC were significantly associated with elevated CAC scores.",
            "output": [
                "Is osteoprotegerin a Better Serum Biomarker of Coronary Artery Calcification than Osteocalcin in Type 2 Diabetes?"
            ]
        },
        {
            "id": "task847-239819f948264fc7bd5f56599047fb9c",
            "input": "We hypothesized that variability from year to year in how much of the bone map was filled in at the bottom of the spine region of interest (ROI) contributes substantially to variability in measurement of spine bone mineral density (BMD).', 'A total of 110 spine BMDs with defects in the bone mapping at the bottom were reanalyzed, with the only change being manually drawing a straight line across the bottom of the ROI and filling in the bone map.', 'The mean (SD) change in area, bone mineral content, and BMD for total spine when the bottom of the bone map was filled in was 0.919 (0.411) cm2, 0.201 (0.121) g, and -0.0098 (0.0043) g/cm2, respectively, and all changes were significant (P<.0001). The largest individual change in total spine BMD with reanalysis was 0.0238 g/cm2, close to the least significant change (LSC) of 0.026 g/cm2 in our center. To quantify variability due to this change in analysis, we calculated an LSC(fill), in which the pairs of scans consisted of the same scan before and after filling in the bottom of the spine bone map, without any other change. The LSC(fill) attributable just to the reanalysis of missing bone map at the bottom of the spine was 0.021 g/cm2, suggesting substantial variance due to variability in mapping the bottom of the spine.",
            "output": [
                "Does inconsistency in filling in the bottom of the spine bone map affect reported spine bone mineral density?"
            ]
        },
        {
            "id": "task847-0945f0cb19494484b21da9e2abda26fa",
            "input": "Chronic intermittent hypobaric hypoxia (CIHH) protects the heart against ischemia/reperfusion (I/R) injury. This study investigated the calcium homeostasis mechanism and the role of Na(+)/Ca(2+) exchanger (NCX) in the cardiac protective effect of CIHH in developing rats.', 'Neonatal male rats received CIHH treatment or no treatment (control) in a hypobaric chamber simulating 3000-meter altitude for 42 days. The left ventricular function of isolated hearts was evaluated after 30 minutes of ischemia and 60 minutes of reperfusion. Myocardial infarct size, intracellular Ca(2+) concentration ([Ca(2+)]i), Na(+)-Ca(2+) exchanger currents (I(Na/Ca)) in ventricular myocytes, and NCX1 protein level in the sarcolemmal membrane were determined.', 'The recovery of cardiac function after I/R was improved, with the myocardial infarct size reduced, in CIHH rats compared with control rats (p<0.05). These effects were attenuated by Bay K8644, an L-type Ca(2+) channel agonist, or ryanodine, a sarcoplasmic reticulum Ca(2+) channel receptor activator. Furthermore, the increases in [Ca(2+)]i during I/R were blunted in CIHH rats, but this effect was abolished by Bay K8644 or chelerythrine, a protein kinase C (PKC) inhibitor. The I(Na/Ca) was decreased and the reversal potential of INa/Ca was shifted toward negative potential during simulated ischemia in the control cardiomyocytes (p<0.05). The inhibition of NCX1 protein expression during I/R was smaller in the CIHH rats than in the control rats (p<0.05).",
            "output": [
                "Does chronic intermittent hypobaric hypoxia ameliorate ischemia/reperfusion-induced calcium overload in heart via Na/Ca2+ exchanger in developing rats?"
            ]
        },
        {
            "id": "task847-317aef7cdca44961b9cda585faaa4666",
            "input": "Diffusion-weighted MRI (DWI) has been used in neurosurgical practice mainly to distinguish cerebral metastases from abscess and glioma. There is evidence from other solid organ cancers and metastases that DWI may be used as a biomarker of prognosis and treatment response. We therefore investigated DWI characteristics of cerebral metastases and their peritumoral region recorded pre-operatively and related these to patient outcomes.', 'Retrospective analysis of 76 cases operated upon at a single institution with DWI performed pre-operatively at 1.5T. Maps of apparent diffusion coefficient (ADC) were generated using standard protocols. Readings were taken from the tumor, peritumoral region and across the brain-tumor interface. Patient outcomes were overall survival and time to local recurrence.', 'A minimum ADC greater than 919.4 \u00d7 10(-6) mm(2)/s within a metastasis predicted longer overall survival regardless of adjuvant therapies. This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer. The change in diffusion across the tumor border and into peritumoral brain was measured by the \"ADC transition coefficient\" or ATC and this was more strongly predictive than ADC readings alone. Metastases with a sharp change in diffusion across their border (ATC >0.279) showed shorter overall survival compared to those with a more diffuse edge. The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 - 0.97, p = 0.04).",
            "output": [
                "Does diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predict patient outcomes?"
            ]
        },
        {
            "id": "task847-e4fe8af56b044815b84d6950b437598d",
            "input": "Impairment of proteasomal function is pathogenic in several cardiac proteinopathies and can eventually lead to heart failure. Loss of proteasomal activity often results in the accumulation of large protein aggregates. The ubiquitin proteasome system (UPS) is primarily responsible for cellular protein degradation, and although the role of ubiquitination in this process is well studied, the function of an ancillary post-translational modification, SUMOylation, in protein quality control is not fully understood.', 'To determine the role of ubiquitin-conjugating enzyme 9 (UBC9), a small ubiquitin-like modifier-conjugating enzyme, in cardiomyocyte protein quality control.', 'Gain- and loss-of-function approaches were used to determine the importance of UBC9. Overexpression of UBC9 enhanced UPS function in cardiomyocytes, whereas knockdown of UBC9 by small interfering RNA caused significant accumulations of aggregated protein. UPS function and relative activity was analyzed using a UPS reporter protein consisting of a short degron, CL1, fused to the COOH-terminus of green fluorescent protein (GFPu). Subsequently, the effects of UBC9 on UPS function were tested in a proteotoxic model of desmin-related cardiomyopathy, caused by cardiomyocyte-specific expression of a mutated \u03b1B crystallin, CryAB(R120G). CryAB(R120G) expression leads to aggregate formation and decreased proteasomal function. Coinfection of UBC9-adenovirus with CryAB(R120G) virus reduced the proteotoxic sequelae, decreasing overall aggregate concentrations. Conversely, knockdown of UBC9 significantly decreased UPS function in the model and resulted in increased aggregate levels.",
            "output": [
                "Is sumo E2 enzyme UBC9 required for efficient protein quality control in cardiomyocytes?"
            ]
        },
        {
            "id": "task847-04e49b1677a94adaaac8117828c29a1f",
            "input": "In multiple sclerosis (MS), pathological studies have identified substantial demyelination and neuronal loss in the spinal cord grey matter (GM). However, there has been limited in vivo investigation of cord GM abnormalities and their possible functional effects using MRI combined with clinical evaluation.', 'We recruited healthy controls (HC) and people with a clinically isolated syndrome (CIS), relapsing remitting (RR) and secondary progressive (SP) MS. All subjects had 3 T spinal cord MRI with measurement of cord cross-sectional area and diffusion tensor imaging metrics in the GM and posterior and lateral column white matter tracts using region of interest analysis. Physical disability was assessed using the expanded disability status scale (EDSS) and motor components of the MS functional composite scale. We calculated differences between MS and HC using a ANOVA and associations with disability using linear regression.', '113 people were included in this study: 30 controls, 21 CIS, 33 RR and 29 SPMS. Spinal cord radial diffusivity (RD), fractional anisotropy and mean diffusivity in the GM and posterior columns were significantly more abnormal in SPMS than in RRMS. Spinal cord GM RD (\u03b2=0.33, p<0.01) and cord area (\u03b2=-0.45, p<0.01) were independently associated with EDSS (R(2)=0.77); spinal cord GM RD was also independently associated with a 9-hole peg test (\u03b2=-0.33, p<0.01) and timed walk (\u03b2=-0.20, p=0.04).",
            "output": [
                "Are spinal cord grey matter abnormalities associated with secondary progression and physical disability in multiple sclerosis?"
            ]
        },
        {
            "id": "task847-b1c93469835242388fe178258cb5cc82",
            "input": "One third of non-small cell lung cancer (NSCLC) affects elderly patients in a locally advanced (LA) stage. Induction therapy followed by a curative approach is becoming the standard-of-care for LA-NSCLC.', 'We compared the efficacy and tolerance to induction chemotherapy or chemo-radiation followed by surgery or definitive radiotherapy in patients younger (N=64) and older (N=44) than 70 years with LA-NSCLC.', 'Elderly patients trended towards having a worse baseline performance status, and presented a higher percentage of IIIB, and squamous tumors. Nevertheless, no significant differences in response rate, operability, or disease-free and overall survival were found between age groups in the whole series, nor in the sub-group of resected patients. Grade 3-4 toxicity tended to be lower in elderly patients.",
            "output": [
                "Does age worsen the efficacy nor tolerance to combined induction therapies in locally advanced non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-d058d9c3f2434482965030e8824776a0",
            "input": "Successful cancer treatments still require more compounds to be isolated from natural sources. Thus, we have investigated anti-proliferative/apoptotic effects of methanolic extracts of lichen species Parmelia sulcata Taylor and Usnea filipendula Stirt on human lung cancer (A549, PC3), liver cancer (Hep3B) and rat glioma (C6) cells.', 'Anti-proliferative effects were monitored by MTT and adenosine triphosphate viability assays, while genotoxic activity was studied using the comet assay. Additionally, cell death mode and apoptosis assays (fluorescence staining, caspase-cleaved cytokeratin 18, caspase-3 activity and PARP cleavage) were performed.', 'Extracts produced anti-population growth effects in a dose-dependent manner (1.56-100 \u03bcg/ml) by inducing apoptosis-like cell death. This resulted in the lines having the presence of pyknotic cell nuclei. In addition, significant increase in genetic damage in the cell lines was seen, indicating that DNA damage may have been responsible for apoptotic cell death.",
            "output": [
                "Do parmelia sulcata Taylor and Usnea filipendula Stirt induce apoptosis-like cell death and DNA damage in cancer cells?"
            ]
        },
        {
            "id": "task847-3b2baf2eae5141a480fff1edb11ec820",
            "input": "LV hypertrophy (LVH) is frequent after aortic valve replacement (AVR) and is often associated with comorbidities, including hypertension, obesity, renal failure and prosthesis-patient mismatch (PPM). However, whether other biological mechanism(s) may participate to LVH after AVR is still unknown. Parathyroid hormone (PTH) may play a role in LVH. However, it is presently unknown whether PTH is associated with LVH in patients that have undergone an AVR.', 'In this cross-sectional study, 195 patients have been investigated at a mean of 8 \u00b1 3.5 years following AVR. LV function and mass were evaluated by Doppler echocardiography. The plasma levels of PTH, 25-hydroxyvitamin D (25-OHD), calcium and phosphate were measured.', 'There were 102 (52%) patients with LVH after AVR. In univariate analyses, PTH blood level was associated with LV mass (LVMi) and LVH. After adjustment for other risk factors, elevated PTH remained associated with LVMi (p=0.003) and LVH (p=0.02). In turn, the blood levels of 25-OHD and the renal function (GFR) were independently and inversely related to the blood level of PTH.",
            "output": [
                "Is parathyroid hormone associated with the LV mass after aortic valve replacement?"
            ]
        },
        {
            "id": "task847-905164da5fce4fdda0204db293acaec6",
            "input": "Asymmetric cell division (ACD) is a key process that allows different cell types to be generated at precisely defined times and positions. In Drosophila, neural precursor cells rely heavily on ACD to generate the different cell types in the nervous system. A conserved protein machinery that regulates ACD has been identified in Drosophila, but how this machinery acts to allow the establishment of differential cell fates is not entirely understood.', 'To identify additional proteins required for ACD, we have carried out an in\\xa0vivo live imaging RNAi screen for genes affecting the asymmetric segregation of Numb in Drosophila sensory organ precursor cells. We identify Banderuola (Bnd), an essential regulator of cell polarization, spindle orientation, and asymmetric protein localization in Drosophila neural precursor cells. Genetic and biochemical experiments show that Bnd acts together with the membrane-associated tumor suppressor Discs-large (Dlg) to establish antagonistic cortical domains during ACD. Inhibiting Bnd strongly enhances the dlg phenotype, causing massive brain tumors upon knockdown of both genes. Because the mammalian homologs of Bnd and Dlg are interacting as well, Bnd function might be conserved in vertebrates, and it might also regulate cell polarity in higher organisms.",
            "output": [
                "Does the conserved discs-large binding partner Banderuola regulate asymmetric cell division in Drosophila?"
            ]
        },
        {
            "id": "task847-b536e352d1d8415d805f50ba89b3805d",
            "input": "The PINK1-Parkin pathway is known to play important roles in regulating mitochondria dynamics, motility, and quality control. Activation of this pathway can be triggered by a variety of cellular stress signals that cause mitochondrial damage. How this pathway senses different levels of mitochondrial damage and mediates cell fate decisions accordingly is incompletely understood.', 'Here, we present evidence that PINK1-Parkin has both cytoprotective and proapoptotic functions. PINK1-Parkin operates as a molecular switch to dictate cell fate decisions in response to different cellular stressors. Cells exposed to severe and irreparable mitochondrial damage agents such as valinomycin can undergo PINK1-Parkin-dependent apoptosis. The proapoptotic response elicited by valinomycin is associated with the degradation of Mcl-1. PINK1 directly phosphorylates Parkin at Ser65 of its Ubl domain and triggers activation of its E3 ligase activity through an autocatalytic mechanism that amplifies its E3 ligase activity toward Mcl-1.",
            "output": [
                "Does pINK1 trigger autocatalytic activation of Parkin to specify cell fate decisions?"
            ]
        },
        {
            "id": "task847-4bffc196d75e48079c22de0a1a55644c",
            "input": "A complex network of putative molecular interactions underlies the architecture and function of cell-matrix adhesions. Most of these interactions are implicated from coimmunoprecipitation studies using expressed components, but few have been demonstrated or characterized functionally in living cells.', 'We introduce fluorescence fluctuation methods to determine, at high spatial and temporal resolution, \"when\" and \"where\" molecular complexes form and their stoichiometry in nascent adhesions (NAs). We focus on integrin-associated molecules implicated in integrin activation and in the integrin-actin linkage in NAs and show that these molecules form integrin-containing complexes hierarchically within the adhesion itself. Integrin and kindlin reside in a molecular complex as soon as adhesions are visible; talin, although also present early, associates with the integrin-kindlin complex only after NAs have formed and in response to myosin II activity. Furthermore, talin and vinculin association precedes the formation of the integrin-talin complex. Finally, \u03b1-actinin enters NAs periodically and in clusters that transiently associate with integrins. The absolute number and stoichiometry of these molecules varies among the molecules studied and changes as adhesions mature.",
            "output": [
                "Do integrin-associated complexes form hierarchically with variable stoichiometry in nascent adhesions?"
            ]
        },
        {
            "id": "task847-62fec0d8c08d49d79ac47cf0761e0fd5",
            "input": "In humans, glucocorticoid-induced osteoporosis is the most common cause of medication-induced osteoporosis. Recent clinical data suggest that glucocorticoid therapy increases the risk of vertebral fractures within a short treatment period. Therefore, this study aimed at investigating vertebral bone in a rat model of glucocorticoid-induced postmenopausal osteoporosis.', 'Fifty Sprague-Dawley rats were randomly assigned into three groups: 1) untreated controls, 2) Sham-operated group, and 3) ovariectomized rats treated with glucocorticoid (dexamethasone) for 3 months (3M) after recovery from bilateral ovariectomy. Osteoporotic bone status was determined by means of the gold standard dual energy X-ray absorptiometry (DEXA) scan. Vertebral bodies were examined using \u00b5CT, histological analysis, mRNA expression analysis, and biomechanical compression testing. Further systemic effects were studied biochemically using serum marker analysis.', 'Dexamethasone treatment showed at 3M a significantly lower bone mineral density in ovariectomized rats compared to Sham-operated control (p < 0.0001) as analyzed in vivo by DEXA. Furthermore, Z scores reached levels of -5.7 in the spine indicating sever osteoporotic bone status. Biomechanical testing of compression stability indicated a lower functional competence (p < 0.0001) in the spine of treated rats. \u00b5CT analysis showed significant reduction of bone volume density (BV/TV%; p < 0.0001), significantly enhanced trabecular spacing (Tb.Sp; p < 0.0001) with less trabecular number (Tb.N; p < 0.001) and complete loss of trabecular structures in glucocorticoid-treated ovariectomized rats. Histological analysis by osteoblast and osteoclast activities reflected a higher bone catabolism reflected by osteoclast counts by TRAP (p < 0.019) and lower bone catabolism indicated by ALP-stained area (p < 0.035).Serum analysis showed a significant increase in osteocalcin (p < 0.0001), osteopontin (p < 0.01) and insulin (p < 0.001) at 3M. Expression analysis of molecular markers in the vertebral body revealed lower expression in tenascin C in the OVX-steroid animals at 3M.",
            "output": [
                "Does short-term glucocorticoid treatment cause spinal osteoporosis in ovariectomized rats?"
            ]
        },
        {
            "id": "task847-736f96ef32604df8a2687f24d301b5df",
            "input": "Adult acquired flatfoot deformity is characterized by midfoot abduction and collapse of the medial longitudinal arch. Lateral column lengthening osteotomies primarily correct the abduction deformity, but the effects of graft shape on deformity correction and forefoot loading are unclear. Therefore, the purpose of this study was to demonstrate the effect of graft shape and taper on deformity correction and forefoot loading mechanics in a cadaveric flatfoot model.', 'Flatfoot deformity was simulated in 18 cadaveric specimens. A lateral column lengthening osteotomy was performed using a triangular, trapezoidal, and rectangular graft for each specimen. During each testing condition, talonavicular joint angles and forefoot plantar pressures were measured.', 'Each graft shape corrected abduction and dorsiflexion deformity at the talonavicular joint. Coronal plane correction was affected by graft shape, and the less tapered trapezoidal and rectangular grafts overloaded the lateral forefoot compared to the intact condition. The more tapered triangular graft did not cause a lateral shift in forefoot pressures. Forefoot plantar pressures were strongly correlated with talonavicular abduction correction (R (2) = .473, P < .001).",
            "output": [
                "Does graft shape affect midfoot correction and forefoot loading mechanics in lateral column lengthening osteotomies?"
            ]
        },
        {
            "id": "task847-0eac00f4051b462aa9b3daef70e02acb",
            "input": "Frozen Shoulder Syndrome is a fibrosis of the shoulder joint capsule that is clinically associated with Dupuytren's disease, a fibrosis of the palmar fascia. Little is known about any commonalities in the pathophysiology of these connective tissue fibroses. \u03b2-catenin, a protein that transactivates gene expression, and levels of IGF2 mRNA, encoding insulin-like growth factor-II, are elevated in Dupuytren's disease. The aim of this study was to determine if correlating changes in \u03b2-catenin levels and IGF2 expression are evident in Frozen Shoulder Syndrome.\", 'Tissue from patients with Frozen Shoulder Syndrome and rotator cuff tear were obtained during shoulder arthroscopies. Total protein extracts were prepared from tissue aliquots and \u03b2-catenin immunoreactivity was assessed by Western immunoblotting. In parallel, primary fibroblasts were derived from these tissues and assessed for IGF2 expression by quantitative PCR.', '\u03b2-catenin levels were significantly increased in Frozen Shoulder Syndrome relative to rotator cuff tear when assessed by Western immunoblotting analyses. IGF2 mRNA levels were significantly increased in primary fibroblasts derived from frozen shoulder syndrome tissues relative to fibroblasts derived from rotator cuff tissues.",
            "output": [
                "Are iGF2 expression and \u03b2-catenin levels increased in Frozen Shoulder Syndrome?"
            ]
        },
        {
            "id": "task847-911c368fb6f84c55aff9d3d764ab2e83",
            "input": "Vibrio cholerae is a globally dispersed pathogen that has evolved with humans for centuries, but also includes non-pathogenic environmental strains. Here, we identify the genomic variability underlying this remarkable persistence across the three major niche dimensions space, time, and habitat.', 'Taking an innovative approach of genome-wide association applicable to microbial genomes (GWAS-M), we classify 274 complete V. cholerae genomes by niche, including 39 newly sequenced for this study with the Ion Torrent DNA-sequencing platform. Niche metadata were collected for each strain and analyzed together with comprehensive annotations of genetic and genomic attributes, including point mutations (single-nucleotide polymorphisms, SNPs), protein families, functions and prophages.",
            "output": [
                "Does comparative genomics of 274 Vibrio cholerae genomes reveal mobile functions structuring three niche dimensions?"
            ]
        },
        {
            "id": "task847-0ff64cedb45942a48846ed08e23c8cc6",
            "input": "The study investigated the effect of supplementation with maltodextrin (CHO) alone or associated to caffeine during exercise in T2DM subjects.', 'Pilot study, using eight subjects with T2DM, aged 55\u00b110 years, received CHO (1 g/kg) or caffeine (1.5 mg/kg) alone or associated before exercise protocol. The exercise was executed at 40% heart rate (HR) reserve for 40 min, with 10-min recovery. Blood pressure (BP) and perceived exertion scale (Borg) were checked every 2 min. Blood glucose (BG) was checked every 10 min. For statistical analysis, ANOVA test was used and the value was considered statistically significant at p <0.05.', 'The results showed that BP and HR did not change significantly among all treatments. Caffeine promoted a significant reduction in BG of 75 mg/dL (65%, p <0.05) during 40 min of exercise protocol compared to all groups.",
            "output": [
                "Does caffeine modify blood glucose availability during prolonged low-intensity exercise in individuals with type-2 diabetes?"
            ]
        },
        {
            "id": "task847-38eb9f272e744a20b2b00d4aa60d3c4e",
            "input": "To examine the relationship between changes in objectively assessed sleep and global cognitive functioning from inpatient postacute rehabilitation to 6-month follow-up.', 'Secondary analysis of two prospective, longitudinal studies.', 'Inpatient rehabilitation units at a Veterans Affairs Medical Center.', 'Older adults (mean age 73.8 \u00b1 9.4) undergoing inpatient rehabilitation (n = 192).', 'All participants completed 7 nights and days of ambulatory sleep monitoring using wrist actigraphy (yielding an estimate of nighttime wakefulness and daytime sleep) and the Mini-Mental State Examination (MMSE) during a postacute inpatient rehabilitation stay and 6 months after discharge. The 5-item Geriatric Depression Scale, Geriatric Pain Measure, and Cumulative Illness Rating Scale for Geriatrics were completed during inpatient rehabilitation.', 'Growth curve modeling (controlling for baseline age, education, sex, body mass index, depression, pain, and comorbidity burden) revealed that individuals whose amount of daytime sleep decreased from inpatient postacute rehabilitation to 6-month follow-up also experienced improvements in MMSE score (\u03b2 = -0.01, t(80 = -3.22, P = .002)). Change in nighttime wakefulness was not a significant predictor of change in MMSE score.",
            "output": [
                "Is decrease in daytime sleeping associated with improvement in cognition after hospital discharge in older adults?"
            ]
        },
        {
            "id": "task847-ca8dc4f5de67464ab35f5bf856093d48",
            "input": "Studies have demonstrated the efficacy of metformin (MTF ) in reducing insulin resistance and N-acetyl cysteine (NAC) in inhibiting oxidative stress which are involved in the pathogenesis of polycystic ovarian syndrome (PCOS). We aimed to compare the effects of MTF and NAC combination on serum metabolite and hormonal levels during the course of ovulation induction in PCOS individual candidates of intracytoplasmic sperm injection (ICSI).', 'In this prospective randomized clinical trial, placebo con- trolled pilot study, 80 patients of polycystic ovarian syndrome at the age of 25-35 years were divided into 4 groups (n=20): i. NAC=treated with N-acetyl cysteine (600 mg three times daily), ii. MTF=treated with metformin (500 mg three times daily), iii. MTF+NAC=treated with N-acetyl cysteine plus metformin (the offered doses) and iv. placebo (PLA). A total number of 20 patients (6 from MTF group, 4 from NAC group, 6 from MTF+NAC group and 4 from PLA group) were dropped of the study. The drugs were administrated from day 3 of menses of previous cycle until ovum pick-up.', 'Serum levels of luteinizing hormone (LH), total testosterone, cholester- ol and triglyceride, insulin and leptin significantly reduced in the MTF and NAC groups compared to the placebo (p<0.01). But levels of LH, total testosterone, cholesterol and triglyceride had no significant reduction in the MTF+NAC groups compared to the placebo. The serum levels of malonyldialdehyde (MDA), insulin and leptin reduced significantly after treatment in the MTF+NAC group compared to the placebo (p<0.05).",
            "output": [
                "Does co-Administration of Metformin and N-Acetyl Cysteine fail to Improve Clinical Manifestations in PCOS Individual Undergoing ICSI?"
            ]
        },
        {
            "id": "task847-66682ffed68b4d25a75cdf04fa7f18fc",
            "input": "Leptin alters bone and mineral metabolism in rodents, but this has not been verified in humans. PATIENTS with congenital generalized lipodystrophy (CGL) have low leptin due to deficient adipose mass and serve as models of leptin deficiency and replacement.', 'To study the effects of recombinant human methionyl leptin (metreleptin) on bone mineral content (BMC) and mineral metabolism.', 'An open-label nonrandomized study at the National Institutes of Health.', 'Thirty-one patients with CGL (ages 4.3 to 46.7 y).', 'Metreleptin (0.06 to 0.24 mg/kg/d) for 6 months to 11 years.', 'BMC was assessed by dual-energy x-ray absorptiometry. SD scores (SDS) for BMC were calculated based on height, race, sex, and age using population normative data. Calcium, phosphorus, PTH, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were measured at baseline and follow-up.', 'At baseline, patients demonstrated significantly increased total body less head BMC (mean SDS, 1.8 \u00b1 0.7), height (mean SDS, 1.3 \u00b1 1.3), and lean mass index, defined as lean body mass per height squared (mean SDS, 1.5 \u00b1 0.83), vs population normative data. No change in total body less head BMC was observed after metreleptin. Lean mass index decreased with metreleptin. Serum calcium decreased with metreleptin, but remained within normal limits. No changes were seen in phosphorus, PTH, or vitamin D.",
            "output": [
                "Is bone mineral content in patients with congenital generalized lipodystrophy unaffected by metreleptin replacement therapy?"
            ]
        },
        {
            "id": "task847-0b625a6caf8f4ea58e97c8ce5d44ebf8",
            "input": "p16(INK4a) Is overexpressed in almost all precancerous and carcinomatous lesions of the uterine cervix, secondary to interference between high-risk human papillomaviruses (hr-HPVs) and the retinoblastoma gene product. Overexpression of p16(INK4a) has also been identified in patients with high-grade urothelial lesions, both cytologically and histologically. However, the etiological role of HPV has not been documented except in inverted papillomas, low-grade bladder tumors, and younger patients. We therefore attempted to verify if HPV DNA was detectable in p16(INK4a) -positive urothelial tumors.', 'A total of 90 urinary cytology samples (33 negative/low-grade cases and 57 high-grade proliferations) were analyzed for p16(INK4a) and HPV DNA. HPV genotyping was performed by polymerase chain reaction using a low-density DNA microarray enabling the detection of 35 HPVs. A reasoned approach combining tissue genotyping and in situ hybridization (ISH) for hr-HPVs was used in patients with urinary HPV.', 'Low-risk HPV (HPV-84) and hr-HPVs (HPV-16, -31, and -70) were detected. The prevalence of hr-HPVs in the urine was low: 5 of 82 patients (6.1%) and only 4 of 50 patients (8.0%) with high-grade urothelial malignancy. p16(INK4a) overexpression was noted in 49 high-grade samples (85.9%). In patients with p16(INK4a) -positive tumor cells and hr-HPV in the urine, HPV genotyping and ISH for hr-HPVs were negative in matched tissue sections.",
            "output": [
                "Is p16 ( INK4a ) overexpression linked to oncogenic human papillomaviruses in patients with high-grade urothelial cancer cells?"
            ]
        },
        {
            "id": "task847-ebc66eb6c8cd458983cd5633a920dc90",
            "input": "To assess disability more efficiently with less burden on the patient, the National Institutes of Health has developed the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function-an instrument based on item response theory and using computer adaptive testing (CAT). Initially, upper and lower extremity disabilities were not separated and we were curious if the PROMIS Physical Function CAT could measure upper extremity disability and the Quick Disability of Arm, Shoulder and Hand (QuickDASH).', 'We aimed to find correlation between the PROMIS Physical Function and the QuickDASH questionnaires in patients with upper extremity illness. Secondarily, we addressed whether the PROMIS Physical Function and QuickDASH correlate with the PROMIS Depression CAT and PROMIS Pain Interference CAT instruments. Finally, we assessed factors associated with QuickDASH and PROMIS Physical Function in multivariable analysis.', 'A cohort of 93 outpatients with upper extremity illnesses completed the QuickDASH and three PROMIS CAT questionnaires: Physical Function, Pain Interference, and Depression. Pain intensity was measured with an 11-point ordinal measure (0-10 numeric rating scale). Correlation between PROMIS Physical Function and the QuickDASH was assessed. Factors that correlated with the PROMIS Physical Function and QuickDASH were assessed in multivariable regression analysis after initial bivariate analysis.', 'There was a moderate correlation between the PROMIS Physical Function and the QuickDASH questionnaire (r=-0.55, p<0.001). Greater disability as measured with the PROMIS and QuickDASH correlated most strongly with PROMIS Depression (r=-0.35, p<0.001 and r=0.34, p<0.001 respectively) and Pain Interference (r=-0.51, p<0.001 and r=0.74, p<0.001 respectively). The factors accounting for the variability in PROMIS scores are comparable to those for the QuickDASH except that the PROMIS Physical Function is influenced by other pain conditions while the QuickDASH is not.",
            "output": [
                "Does the PROMIS physical function correlate with the QuickDASH in patients with upper extremity illness?"
            ]
        },
        {
            "id": "task847-936408eac92a46e797687527b5227fe2",
            "input": "This study was conducted to quantify the effect of multidisciplinary care (MDC) on amputation-free survival (AFS) and wound healing within a chronic critical limb ischemia (CLI) population.', 'We performed a retrospective, single-center cohort study of consecutive CLI patients presenting to the Vascular Surgery Service. Patients who received initial and follow-up wound care from the MDC were compared with patients who received standard wound care (SWC). The MDC team consisted of vascular, plastic, and podiatric surgeons who jointly managed wound care and directed any other consults or services as deemed necessary. SWC consisted of an inconsistent mix of providers without a defined manager, including nurses, wound care midlevel providers, general surgeons, internists, or the patients themselves. The referring physician determined the allocation of patients. The primary outcome variable was AFS, with a secondary evaluation of wound healing. The effects of baseline demographics, comorbid medical conditions, laboratory values, ischemic lesion severity and location, Rutherford classification, and participation in MDC were assessed. Significant univariate predictors (P < .10) of AFS were entered into a multivariate Cox regression model and assessed at an \u03b1 = .05.', 'Between August 2010 and June 2012, 146 CLI patients (91 male [63%]) were evaluated by the Vascular Surgery Service and were followed up for a median of 539 days (interquartile range 314-679 days). Ischemic tissue loss was present in 85 patients (38 at Rutherford category 5, and 47 at Rutherford category 6). Within this cohort, 51 (60%) had MDC, and 34 (40%) had SWC. Fifty-eight patients (68%) underwent revascularization (open in 17, endovascular in 35, and hybrid in 6), 14 (8%) were managed with primary major amputation, and 13 (15%) declined revascularization. AFS was superior for patients in the MDC arm vs the SWC arm (593.3 \u00b1 53.5 days vs 281.0 \u00b1 38.2 days; log-rank, P = .02). Wound-healing times favored the MDC arm over the SWC arm (444.5 \u00b1 33.2 days vs 625.2 \u00b1 126.5 days), although this was not statistically significant (log-rank, P = .74). Multivariate modelling revealed that independent predictors of major amputation or death, or both, were nonrevascularized patients (hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.78-8.02; \u03c7(2), P < .01), treatment by SWC (HR, 2.664; 95% CI, 1.23-5.77; \u03c7(2), P = .012), and baseline nonambulatory status (HR, 1.89; 95% CI, 1.17-2.85; \u03c7(2), P < .01).",
            "output": [
                "Does multidisciplinary care improve amputation-free survival in patients with chronic critical limb ischemia?"
            ]
        },
        {
            "id": "task847-d9dd75d1874748be9ee8e4f844e9be8d",
            "input": "To determine if adolescents with unilateral hearing loss (UHL) demonstrate worse language skills than their siblings with normal hearing (NH).', 'Case-control study of 12-17-year-old adolescents with UHL (20 cases) compared with sibling controls with NH (13 controls).', \"Scores on the oral portion of the Oral and Written Language Scales (OWLS) and the Clinical Evaluation of Language Fundamentals (CELF) were the primary outcome measure. Wechsler's Abbreviated Scales of Intelligence (WASI) scores were also used as an outcome measure.\", 'Adolescents with UHL demonstrated worse overall and expressive language scores than controls, (98 vs. 114, P=0.001; 100 vs. 114, P=0.006) and had significantly lower full scale (98 vs. 112, P=0.017), verbal (101 vs. 113, P=0.032), and performance IQ (95 vs. 107, P=0.037).",
            "output": [
                "Is unilateral hearing loss associated with a negative effect on language scores in adolescents?"
            ]
        },
        {
            "id": "task847-5e502f7c073543a3abe026a18f20d490",
            "input": "A high catabolic rate characterizes the acute phase of critical illness. Guidelines recommend an early nutritional support, regardless of the previous nutritional status.', 'We aimed to assess whether the nutritional status of patients, which was defined by the body mass index (BMI) at admission in an intensive care unit (ICU), affected the time of nutritional support initiation.', 'We conducted a cohort study that reported a retrospective analysis of a multicenter ICU database (OUTCOMEREA) by using data prospectively entered from January 1997 to October 2012. Patients who needed orotracheal intubation within the first 72 h and >3 d were included.', 'Data from 3257 ICU stays were analyzed. The delay before feeding was different according to BMI groups (P = 0.035). The delay was longer in obese patients [BMI (in kg/m\u00b2) \u226530; n = 663] than in other patients with either low weight (BMI <20; n = 501), normal weight (BMI \u226520 and <25; n = 1135), or overweight (BMI \u226525 and <30; n = 958). The association between nutritional status and a delay in nutrition initiation was independent of potential confounding factors such as age, sex, and diabetes or other chronic diseases. In comparison with normal weight, the adjusted RR (95% CI) associated with a delayed nutrition initiation was 0.92 (0.86, 0.98) for patients with low weight, 1.00 (0.94, 1.05) for overweight patients, and 1.06 (1.00, 1.12) for obese patients (P = 0.004).",
            "output": [
                "Is initiation of nutritional support delayed in critically ill obese patients : a multicenter cohort study?"
            ]
        },
        {
            "id": "task847-cf375d94ebb346e2838fc61791cce28f",
            "input": "To study the effects of Gambogenic acid (GNA) on the growth of human gastric carcinoma cell line MGC-803 and its underlying mechanisms.', 'MTT assay was used to measure the cell viability. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) were detected using flow cytometry method. Among them, Annexin V-FITC/PI double staining was employed in the analysis of apoptosis, Rh123 in analyzing MMP and H2DCFDA in analyzing ROS formation. P53 expression was confirmed by Western blot.', '4.0 micromol/L GNA inhibited MGC-803 cells growth in a time dependent manner from 24 to 48 h. At the concentration range from 1.0 to 12.0 micromol/L, the inhibitory effect was in a concentration dependent manner. After treatment with 4.0 micromol/L GNA for 48 h, apoptosis was obviously observed as assayed by Annexin V-FITC/PI staining. Importantly, MMP was decreased and ROS formation was increased following GNA treatment. Additionally, P53 expression was up-regulated following 4.0 micromol/ L GNA treatment in a time dependent manner.",
            "output": [
                "Does [ Gambogenic acid induce mitochondria-dependent apoptosis in human gastric carcinoma cell line ]?"
            ]
        },
        {
            "id": "task847-aaa4233a75b542a3a24af14c009eb536",
            "input": "Cigarette smoking is correlated with other risk factors for gout such as adiposity and alcohol intake. The goal of this study was to study the direction and magnitude of association between cigarette smoking and risk for gout.', 'We analysed 54-year follow-up data (1948-2002) for 2279 men and 2785 women who were gout-free at their first assessment as a part of the Framingham Heart Study. Using Cox proportional hazards models we estimated the association between cigarette smoking and incident gout among men and women separately after adjusting for age, BMI, alcohol intake, hypertension, kidney disease and diabetes.', 'There were 399 incident cases (249 men and 150 women) of gout over 151 058 person-years of observation. Incidence rates of gout per 1000 person-years for smokers and non-smokers were 2.13 (95% CI 1.79, 2.53) and 3.04 (95% CI 2.70, 3.42), respectively. In multivariable Cox models, cigarette smoking was associated with gout with a hazard ratio of 0.76 (95% CI 0.59, 0.98) overall, 0.68 (95% CI 0.49, 0.93) among men and 0.92 (95% CI 0.60, 1.41) among women. Lower risk for smokers was evident among all obesity categories, but not among women. Sensitivity analysis suggested that the magnitude of the true odds ratio might be lower than our calculations.",
            "output": [
                "Is cigarette smoking associated with a reduction in the risk of incident gout : results from the Framingham Heart Study original cohort?"
            ]
        },
        {
            "id": "task847-dca357d8ac91494984dbb2a4b496902e",
            "input": "Comorbidity among childhood mental health symptoms is common in clinical and community samples and should be accounted for when investigating etiology. We therefore aimed to uncover latent classes of mental health symptoms in middle childhood in a community sample, and to determine the latent genetic and environmental influences on those classes.', 'The sample comprised representative cohorts of twins. A questionnaire-based assessment of mental health symptoms was used in latent class analyses. Data on 3223 twins (1578 boys and 1645 girls) with a mean age of 7.5 years were analyzed. The sample was predominantly non-Hispanic Caucasian (92.1%).', 'Latent class models delineated groups of children according to symptom profiles--not necessarily clinical groups but groups representing the general population, most with scores in the normative range. The best-fitting models suggested 9 classes for both girls and boys. Eight of the classes were very similar across sexes; these classes ranged from a \"Low Symptom\" class to a \"Moderately Internalizing & Severely Externalizing\" class. In addition, a \"Moderately Anxious\" class was identified for girls but not boys, and a \"Severely Impulsive & Inattentive\" class was identified for boys but not girls. Sex-combined analyses implicated moderate genetic influences for all classes. Shared environmental influences were moderate for the \"Low Symptom\" and \"Moderately Internalizing & Severely Externalizing\" classes, and small to zero for other classes.",
            "output": [
                "Does relative influence of genetics and shared environment on child mental health symptoms depend on comorbidity?"
            ]
        },
        {
            "id": "task847-431f7c03eb204cadba54b86d19f517fe",
            "input": "Gestational diabetes mellitus (GDM) may be an expression of early metabolic syndrome. It is unknown whether weight and/or glucose parameters assessed at GDM pregnancies predict the risk of metabolic syndrome at the early postpartum period.', 'A group of women with GDM (N=1512) was evaluated at 3-11 months postpartum. Incident cases of diabetes were excluded. Antenatal measurements of GDM severity, third-trimester average glycated hemoglobin levels, prepregnancy body mass index (BMI), and increased gestational weight gain were considered. The predictive capability of these factors for postpartum metabolic syndrome was estimated.', 'The prevalence of postpartum metabolic syndrome was 10.9%. The three most common features of metabolic syndrome were low levels of high-density lipoprotein cholesterol (31.2%), high fasting glucose values (23.5%), and a high waist circumference (22.8%). The main predictors of metabolic syndrome were overweight or obesity prepregnancy and high antenatal fasting glycemia. This analysis was adjusted for family history of diabetes, prior GDM, dyslipidemia before pregnancy, chronic arterial hypertension, age, and smoking. The model area 95% confidence interval under the receiver operating characteristic curve was 0.87 (0.84-0.90) for metabolic syndrome presence. The risk for metabolic syndrome was progressively increased as risk factors were added (P<0.001 for trend). When obesity and high fasting glycemia were combined, a multiplied effect ensued.",
            "output": [
                "Are prepregnancy body mass index and prenatal fasting glucose effective predictors of early postpartum metabolic syndrome in Spanish mothers with gestational diabetes?"
            ]
        },
        {
            "id": "task847-928e446185a7494bb7e6eb0375f57a1e",
            "input": "A subset of human hepatocellular carcinomas (HCC) exhibit mutations of \u03b2-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO).', 'Immunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1.', 'Crisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro.",
            "output": [
                "Does glutamine depletion by crisantaspase hinder the growth of human hepatocellular carcinoma xenografts?"
            ]
        },
        {
            "id": "task847-5beb4be23b1c4b2685f41babb3986785",
            "input": "GRAF is a recognized tumor suppressor gene that was found inactivated in AML. However, the prognostic role of a GRAF transcript has not been studied in patients with AML.', 'In this study, we investigated the expression of the GRAF transcript by real time quantitative PCR in 60 AML patients and 30 healthy age and sex matched controls.', 'GRAF expression was significantly lower in patients with AML when compared to controls (P=0.008). There were no significant differences in clinical features, FAB subtypes and cytogenetic risk subgroups between patients with high and low GRAF expression levels. Kaplan-Meier analysis showed that patients with high GRAF expression had longer overall survival (OS). Multivariate analysis revealed that, besides WBC count, GRAF expression was also an independent prognostic factor for AML.",
            "output": [
                "Is high expression of GTPase regulator associated with the focal adhesion kinase ( GRAF ) a favorable prognostic factor in acute myeloid leukemia?"
            ]
        },
        {
            "id": "task847-c54ec23a4e0e477eaca4b94102c6dc71",
            "input": "The clinical trial design for primary progressive multiple sclerosis (PPMS) requires understanding of disability progression in modern patient cohorts.', 'The objective of this paper is to characterize demographic and clinical characteristics of PPMS and assess rate of disability progression.', \"We studied PPMS (n = 73) and relapsing-onset MS (ROMS) patients (n = 1541) enrolled in CLIMB, a longitudinal study of MS patients at the Brigham and Women's Hospital (Boston, MA). Disability progression for each group was compared using interval-censored survival analysis and time to six-month sustained progression.\", 'The PP group had a 1.09:1 male:female ratio compared to 1:2.89 for the RO group and greater mean age of onset (PP: 44.4\u00b19.6; RO: 32.7\u00b19.9; p < 0.0001). Motor symptoms at onset and first symptoms localized to spinal cord were each strongly associated with PPMS (p < 0.001). Median time from onset to EDSS 6.0 was faster in PPMS (p < 0.001). PPMS patients progressed faster to EDSS 3 (p < 0.001) and from EDSS 3 to 6 (p < 0.001). Median time to sustained progression in the PP group was 4.85 years (95% CI 2.83-8.35), significantly faster than the RO group (p < 0.001).",
            "output": [
                "Does progression rates and sample size estimate for PPMS based on the CLIMB study population?"
            ]
        },
        {
            "id": "task847-618c61f7be884594ae0257ba4fd2592b",
            "input": "The aim of this study was to investigate whether microelectronic wear-time documentation can contribute to individualized orthodontic management.', 'The wear times and behaviors of 281 patients undergoing orthodontic treatment with removable appliances were quantified and analyzed using the TheraMon microelectronic system (Sales Agency Gschladt, Hargelsberg, Austria) over a 6-month treatment period.', 'The 281 study participants wore their removable appliances for a median of 9.0 hours per day, compared with the 12 to 15 hours per day prescribed. Wear behavior was variable and heterogeneous in patients with almost identical median wear times, with fluctuating and numerous zero wear-time periods observed.",
            "output": [
                "Does microelectronic wear-time documentation of removable orthodontic devices detect heterogeneous wear behavior and individualizes treatment planning?"
            ]
        },
        {
            "id": "task847-9509aa6a3f6b4e2c9b4e258daacc2522",
            "input": "Urokinase (uPA) modulates cellular and extracellular matrix responses within the microenvironment of the vessel wall and has been shown to activate the epidermal growth factor receptor (EGFR). This study examines the role of the protease domain of uPA during EGFR activation in human vascular smooth muscle cells (VSMC).', 'Human coronary VSMC were cultured in\\xa0vitro. Assays of cell proliferation and EGFR phosphorylation were examined in response to the carboxyterminal fragment of uPA (CTF) in the presence and absence of the plasmin, metalloprotease and a disintegrin and metalloproteinase (ADAM) inhibitors, heparin-bound epidermal growth factor (HB-EGF), and EGFR inhibitors, and small interfering RNA to EGFR and ADAMs.', 'CTF produced a dose-dependent increase in DNA synthesis and cell proliferation in human VSMC, which was blocked in a dose-dependent manner by both plasmin inhibitors and the EGFR inhibitor, AG1478. CTF induced time-dependent EGFR phosphorylation, which was blocked by inhibitors of plasmin and metalloproteinases activity. The presence of urokinase plasminogen activator receptor was not required. Inhibition of ADAM-10 and -12, and of HB-EGF blocked EGFR activation in response to CTF. CTF-mediated activation of EGFR was mediated through G\u03b2\u03b3, src, and NAD(P)H oxidase.",
            "output": [
                "Does protease-mediated human smooth muscle cell proliferation by urokinase require epidermal growth factor receptor transactivation by triple membrane signaling?"
            ]
        },
        {
            "id": "task847-257a3f4112794918a41a5f6a48b89381",
            "input": "The aim of this study was to evaluate and compare microwave disinfection with chemical disinfection of dental gypsum casts.', 'A total of 120 casts were prepared from a silicone mold using Type III dental stone. Of the 120 casts, 60 casts were contaminated with 1 ml suspension of Staphylococcus aureus and 60 casts were contaminated with 1 ml suspension of Pseudomonas aeruginosa. Then, the casts were disinfected with microwave irradiation and chemical disinfection using the microwave oven and 0.5% sodium hypochlorite. Bacteriologic procedures were performed; the cfu/ml for each cast was calculated as a weighted mean. The results were analyzed using Kruskal-Wallis test and Mann-Whitney test.', 'The untreated casts showed Brain heart infusion broth counts of 106 log cfu/ml compared to irradiated and chemically disinfected casts, in which 105 log reduction of cfu/ml was seen. These results satisfied the requirements of current infection control guidelines for the dental laboratory. The results obtained for chemical disinfection were in equivalence with microwave disinfection.",
            "output": [
                "Does evaluation and comparison of high-level microwave oven disinfection with chemical disinfection of dental gypsum cast?"
            ]
        },
        {
            "id": "task847-c1b169e3929e4f46831306321daed892",
            "input": "Neural crest stem cells derived from the boundary cap (bNCSCs), markedly promote survival, proliferation and function of insulin producing \u03b2-cells in vitro and in vivo after coculture/transplantation with pancreatic islets [ 1, 2 ]. Recently, we have shown that beneficial effects on \u03b2-cells require cadherin contacts between bNCSCs and \u03b2-cells [ 3, 4 ]. Here we investigated whether hair follicle (HF) NCSCs, a potential source for human allogeneic transplantation, exert similar positive effects on \u03b2-cells.', 'We established cocultures of HF-NCSCs or bNCSCs from mice expressing enhanced green fluorescent protein together with pancreatic islets from DxRed expressing mice or NMRI mice and compared their migration towards islet cells and effect on proliferation of \u03b2-cells as well as intracellular relations between NCSCs and islets using qRT-PCR analysis and immunohistochemistry.', 'Whereas both types of NCSCs migrated extensively in the presence of islets, only bNCSCs demonstrated directed migration toward islets, induced \u03b2-cell proliferation and increased the presence of cadherin at the junctions between bNCSCs and \u03b2-cells. Even in direct contact between \u03b2-cells and HF-NCSCs, no cadherin expression was detected.",
            "output": [
                "Do neural crest stem cells from hair follicles and boundary cap have different effects on pancreatic islets in vitro?"
            ]
        },
        {
            "id": "task847-f6215343a9324307ace322f79fc69d21",
            "input": "To examine the association between breastfeeding pattern and growth in the first year of life.', 'A cross-sectional survey was carried out on 349 mothers with infants <12 months in a rural and a semi-urban community in Mangochi district, Malawi. Data on socio-demographic characteristics, infant weight, length and feeding patterns since birth were collected. Multivariate linear regression was performed to test the association between feeding pattern and infant anthropometric status.', 'Exclusive breastfeeding (EBF) until 6 months was practised by 13.1% semi-urban and 1.3% rural mothers. No infant was exclusively breastfed beyond 6 months. Breastfeeding was continued among all infants who had stopped EBF. Among infants 6-12 months of age, duration of EBF during the first 6 months was positively associated with length-for-age Z-score (LAZ) (regression coefficient=0.19, 95% confidence interval: 0.06, 0.31) in a model adjusted for socio-demographic factors. Urban residence and female gender yielded positive associations in the same model. The model explained 27% of the variation in LAZ. Among infants <6 months, duration of EBF was not significantly associated with LAZ, but being female and urban residence yielded positive associations. Breastfeeding patterns were not associated with weight-for-age Z-score (WAZ) or weight-for-height Z-score (WLZ) either in the 0-6-month or in the 6-12-month group. Birth outside a health facility was negatively associated with WAZ and WLZ in the older group.",
            "output": [
                "Is exclusive breastfeeding duration during the first 6 months of life positively associated with length-for-age among infants 6-12 months old , in Mangochi district , Malawi?"
            ]
        },
        {
            "id": "task847-8efb6c4d12574e5eb207dcc076592da0",
            "input": "Monkey 20\u03b1-hydroxysteroid dehydrogenase (20\u03b1-HSD) is a catabolic enzyme responsible for converting progesterone into biologically inactive 20\u03b1-hydroxyprogesterone, thereby playing a key role in the estrous cycle or pregnancy and allowing ovulation and parturition to occur in most mammalian animals. Monkey 20\u03b1-HSD was highly abundant in ovarian and placental tissues during the pre-ovulation and pre-parturition phase and was primarily localized in the syncytiotrophoblast of the placenta. In this study, we focused on the molecular characterization of the monkey 20\u03b1-HSD promoter region by conducting reporter assays in Chinese hamster ovary (CHO) K1 cells.', \"A reporter assay using constructs of various lengths of the 5'-flanking region (-890-Luc, -513-Luc, -306-Luc, -273-Luc, and -70-Luc) revealed that a region corresponding to the activator protein 1 (Ap-1) located between -281 and -274 bp was essential for the transcriptional activity. Absence of the Ap-1 site in -273-Luc dramatically decreased the transcription levels to the control levels. When the reporter constructs were co-transfected with Ap-1 (Jun) and specificity protein (Sp-1) genes, the transcription activities of the constructs increased with the exception of -273 and -70, while that of the double construct was reduced compared to that of Ap-1 alone. Furthermore, mutational analysis demonstrated that a putative Ap-1 site played an important role in the expression of the reporter gene. These findings were confirmed by EMSA examining the interactions of the protein Ap-1 in a nuclear extract from CHO-K1 cells and the expression levels of the Ap-1 transcription factor in pre-parturition placenta and CHO-K1 cells. Although mut-1 and mut-2 of Ap-1 bound with nuclear extracts from CHO-K1 cells, the transcriptional activity of mut-3 was almost completely suppressed.",
            "output": [
                "Does the transcription factor Ap-1 regulate monkey 20\u03b1-hydroxysteroid dehydrogenase promoter activity in CHO cells?"
            ]
        },
        {
            "id": "task847-d6f9d9e87b7f4dfeb9b80b63a1822451",
            "input": "Anxiety disorders increase risk of future cardiovascular disease (CVD) and mortality, even after controlling for confounds including smoking, lifestyle, and socioeconomic status, and irrespective of a history of medical disorders. While impaired vagal function, indicated by reductions in heart rate variability (HRV), may be one mechanism linking anxiety disorders to CVD, prior studies have reported inconsistent findings highlighting the need for meta-analysis.', 'Studies comparing resting-state HRV recordings in patients with an anxiety disorder as a primary diagnosis and healthy controls were considered for meta-analysis.', \"Meta-analyses were based on 36 articles, including 2086 patients with an anxiety disorder and 2294 controls. Overall, anxiety disorders were characterized by lower HRV [high frequency (HF): Hedges' g\\u2009=\\u2009-0.29. 95% CI: -0.41 to -0.17, p\\u2009<\\u20090.001; time domain: Hedges' g\\u2009=\\u2009-0.45, 95% CI: -0.57 to -0.33, p\\u2009<\\u20090.001] than controls. Panic disorder (n\\u2009=\\u2009447), post-traumatic stress disorder (n\\u2009=\\u2009192), generalized anxiety disorder (n\\u2009=\\u200968), and social anxiety disorder (n\\u2009=\\u200990), but not obsessive-compulsive disorder (n\\u2009=\\u200940), displayed reductions in HF HRV relative to controls (all ps\\u2009<\\u20090.001).",
            "output": [
                "Are anxiety Disorders Associated with Reduced Heart Rate Variability : A Meta-Analysis?"
            ]
        },
        {
            "id": "task847-1560a6b71e8c4674a19aa6217fcdd737",
            "input": "Indication for rotating hinge (RH) total knee arthroplasty (TKA) includes primary and revision cases, with contradictory results. The aim of this study was to report prospective early results of a new modular rotating hinge TKA (EnduRo). For this implant several new design features and a new bearing material (carbon-fiber reinforced poly-ether-ether-ketone) have been developed. Furthermore, we tried to establish a new classification of failure modes for revision TKA.', '152\\u2009EnduRo rotating-hinge prostheses were implanted in two centers. In 90 patients a primary implantation has been performed and 62 patients were revision cases. Knee Society Score (KSS), Western Ontario and McMaster Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), and Range of motion (ROM) were assessed before surgery, 3 months postoperatively, 12 months postoperatively, and annually thereafter. We defined 3 types of complications: Type 1, infection; type 2, periprosthetic complications; type 3, implant failures.', 'KSS, WOMAC, OKS, and ROM revealed significant improvements between the preoperative and the follow-up investigations. There were 14 complications (9.2%) leading to revision surgery, predominantly type 2.",
            "output": [
                "Do early results of a new rotating hinge knee implant?"
            ]
        },
        {
            "id": "task847-12cb9ea907ab45f4802344798ba3e00e",
            "input": "To investigate the effects of Artemisia lavandulaefolia essential oil on apoptosis and necrosis of HeLa cells.', 'Cell viability was assayed using MTT method. The morphological and structure alterations in HeLa cells were observed by microscopy. Furthermore, cell apoptosis was measured by DNA Ladder and flow cytometry. DNA damage was measured by comet assay, and the protein expression was examined by Western blot analysis.', 'MTT assay displayed essential oil from Artemisia lavandulaefolia could inhibit the proliferation of HeLa cells in a dose-dependent manner. After treated with essential oil of Artemisia lavadulaefolia for 24 h, HeLa cells in 100 and 200 microg/mL experiment groups exhibited the typical morphology changes of undergoing apoptosis, such as cell shrinkage and nucleus chromatin condensed. However, the cells in the 400 microg/mL group showed the necrotic morphology changes including cytomembrane rupture and cytoplasm spillover. In addition, DNA Ladder could be demonstrated by DNA electrophoresis in each experiment group. Apoptosis peak was also evident in flow cytometry in each experiment group. After treating the HeLa cells with essential oil of Artemisia lavadulaefolia for 6 h, comet tail was detected by comet assay. Moreover, western blotting analysis showed that caspase-3 was activated and the cleavage of PARP was inactivated.",
            "output": [
                "Does [ Essential oil from Artemisia lavandulaefolia induce apoptosis and necrosis of HeLa cells ]?"
            ]
        },
        {
            "id": "task847-eb4eec863f2c4da9a3a59c6625b75684",
            "input": "To investigate the effect of targeted antiosteosarcoma methotrexate-bisphosphonate conjugate on growth inhibition and apoptosis in human osteosarcoma MG-63 cells.', 'MG-63 cells were treated with various concentrations of methotrexate-bisphosphonate conjugate and apoptosis was monitored via an MTT assay, cell morphology, TUNEL assay and flow cytometry analysis.', 'The survival rate of MG-63 cells treated for 24 to 96 hours with 2000 mg/ml or more of methotrexate-bisphosphonate conjugate decreased significantly. Cells treated with conjugate showed typical apoptotic features using inverted phase contrast microscopy and fluorescence staining, and the majority of cells demonstrated a positive result in the TUNEL assay. Karyopyknosis and crescent aggregation of chromatin were observed in conjugate-treated cells by electron microscopy. Flow cytometry of MG-63 cells treated with methotrexate-bisphosphonate conjugate showed a time and dose-dependent increase in apoptosis (p < 0.05).",
            "output": [
                "Does targeted antiosteosarcoma methotrexate-bisphosphonate conjugate induce apoptosis of osteosarcoma cells in vitro?"
            ]
        },
        {
            "id": "task847-af5a3c2e1ca5408d8327dedfbca65426",
            "input": "To prove that DNA damage, intracellular reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential (MMP) are contributing factors for the inhibition of cell proliferation induced by doxorubicin (DOX) administration combined with microbubble-assisted low-level therapeutic ultrasound (US) in K562 cells.', '3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was adopted to examine cytotoxicity of different treatments. Changes on apoptosis and necrosis rates, DNA fragmentation, intracellular reactive oxygen species production, mitochondrial membrane potential, cellular membrane permeability and DOX-uptake were analysed by flow cytometry. Nuclear morphology changes were observed under a fluorescence microscope. Ultrasonic cavitation was measured by spectrofluorimetry.', 'Under optimal conditions, MB-US significantly aggravated DOX-induced K562 cell death, especially necrosis, when compared with either monotherapy. Synergistic potentiation on DNA damage, ROS generation and MMP loss were observed. Ultrasonic cavitation effects, plasma membrane permeabilization and DOX-uptake were notably improved after MB-US exposure.",
            "output": [
                "Does activation of microbubbles by low-level therapeutic ultrasound enhance the antitumor effects of doxorubicin?"
            ]
        },
        {
            "id": "task847-d935dadb140d497da809b55df5f6218f",
            "input": "Intact surface active agent (surfactant) composed of surfactant-associated proteins (SPs) and lipids is necessary for respiration and prevents alveoli from collapsing. CD26, a transmembrane glycoprotein exerting dipeptidyl peptidase activity (DPP4), highly expressed in lung parenchyma, is involved in inflammatory processes. A pharmacological inhibition of DPP4 influenced not only the inflammation but also elevated the SPs. Thus, DPP4 inhibitors may be a novel drug for treatment of diseases with surfactant deficiency. Therefore, we tested firstly the hypothesis that DPP4 inhibitors increase the expression of SPs in healthy rats.', 'SP mRNA and protein expression were determined different times after nebulization of aerosolized DPP4 inhibitors [L-isoleucine-thiazolidide (L-Ile-Thia), L-valine-pyrrolidide (L-Val-Pyrr)], budesonide, saline or stereoisomers.', 'Compared with negative controls (1) L-Ile-Thia as well as budesonide led to a significant higher and L-Val-Pyrr had the tendency to a significant higher expression of SP-A mRNA 6 h after nebulization, (2) the expression of SP-D mRNA increased significantly 6 h after nebulization with L-Ile-Thia and 3 and 6 h after nebulization with Val-pyrr, (3) SP-B mRNA levels showed significantly higher values 3 and 6 h after nebulization with L-Val-Pyrr, (4) protein levels of SP-A, SP-B and SP-C were elevated significantly 6 h after nebulization with L-Val-Pyrr as well as with budesonide, and (5) phospholipids were also increased in response to DPP4 inhibition; the minimal surface tension was comparable.",
            "output": [
                "Do dPP4 inhibitors increase differentially the expression of surfactant proteins in Fischer 344 rats?"
            ]
        },
        {
            "id": "task847-34e5e579df51490ba1cec0d5d8c6223d",
            "input": "Recently, there has been increasing concern about adverse health effects of exposure to desert dust events. However, the association between dust and the incidence of ischemic heart diseases is unknown. The aim of the present study was to elucidate whether Asian dust (AD), a windblown sand dust originating from mineral soil in China and Mongolia, is associated with the incidence of acute myocardial infarction (AMI).', 'We investigated the data regarding hospitalization because of AMI among 3068 consecutive patients from 4 AMI centers in Fukuoka, Japan, and data for AD from April 2003 to December 2010. We applied a time-stratified case-crossover design to examine the association between AD and the incidence of AMI. Using a conditional logistic regression analysis, we estimated the odds ratios of AMI associated with AD after controlling for ambient temperature and relative humidity. The occurrence of AD events 0 to 4 days before the day of admission was significantly associated with the incidence of AMI. In particular, the occurrence of AD 4 days before admission was significantly associated with the onset of AMI.",
            "output": [
                "Is desert dust a risk factor for the incidence of acute myocardial infarction in Western Japan?"
            ]
        },
        {
            "id": "task847-6e2969bbd38f467488b0d6ce95e179e1",
            "input": "Photodynamic therapy with aminolevulinic acid (ALA-PDT) is effective therapy for acne vulgaris; however, relatively strong side effects limit its wide usage. We have previously demonstrated that ALA-induced protoporphyrin IX distribution with lower concentrations and shorter contact time of ALA resulted in focused damage in sebaceous glands in vivo. We have formulated a protocol for ALA-PDT using 5% ALA with 2 hours contact time. The objective of this study was to establish the effectiveness and side effect profile of the new protocol in humans.', \"Eleven Japanese patients (Fitzpatrick's skin type III - IV, mean age 23.7\u00b17.2) with facial acne received topical application of 5% ALA for 2 hours with subsequent illumination by a broadband light (600 - 1100 nm, 15J/cm(2), 60 mW/cm(2)). Subjects were evaluated prior to the procedure, 1 month, and 3 months after the treatment by a blinded dermatologist using the global acne grading system (GAGS). Side effects were monitored through the treatment period.\", 'The mean GAGS score decreased from 22.1\u00b13.8 at baseline to 19.4 at 1 month, and to 16.3 at 3 months after PDT (P<0.05). Ten of eleven patients experienced local side effects, such as erythema, which were of minimal to mild severity. However, most side effects were of minimal to mild severity, and all of them resolved within several days without post inflammatory hyper pigmentation.",
            "output": [
                "Is photodynamic Therapy with 5 % \u03b4-Aminolevulinic Acid Safe and Effective Treatment of Acne Vulgaris in Japanese Patients?"
            ]
        },
        {
            "id": "task847-bfb6d94068c040309013c75ae5908f40",
            "input": "To investigate the risk of adhesions after laparoscopic myomectomy (LM). To establish the percentage of adhesions, their kind, situation and magnitude.', 'For the period form June 2011 to November 2013 totally 81 patients were operated by LM. In the study only patients with intramural leymyomas bigger than 5 sm were included. For this period 14 patients had second-look because of the need of another operation--LS or Ceasarean section. 22 myoma incisions were checked. We established 35.7% adhesions per patient. After LM adnexas were engaged in 14.2%.",
            "output": [
                "Is [ `` Second look '' after laparoscopic myomectomy -- that a prevention of postoperative adhesions ]?"
            ]
        },
        {
            "id": "task847-e35f743a751840029b818129d41d995d",
            "input": "Regenerative endodontics aims to re-establish a functional pulp-dentin complex. First, the root canal system is disinfected primarily by irrigants and medicaments. Triple antibiotic paste (TAP), a commonly used intracanal medicament, has been shown to be directly toxic to stem cells at concentrations greater than 0.1 g/mL. Thus, its complete removal is a crucial step in regenerative endodontic procedures. We hypothesized that currently used irrigation techniques do not completely remove TAP from root canal system.', 'TAP was radiolabeled by the incorporation of I(125), and calcium hydroxide (Ultracal; Ultradent, South Jordan, UT) was radiolabeled with Ca(45). The intracanal medicaments were placed into standardized human root segments and incubated for 28 days at 37\u00b0C. Then, canals were irrigated with EndoActivator (Dentsply, Tulsa, OK), passive ultrasonic irrigation, EndoVac (SybronEndo, Coppell, TX), or a syringe/Max-i-Probe needle (Dentsply Rinn, Elgin, IL) using a standardized irrigation protocol in a closed system. Radioactivity levels (counts per minute values) were measured for each tooth before and after the irrigation protocols. Furthermore, the canals were sequentially enlarged and dentin samples collected and evaluated for radioactivity. Data were analyzed with analysis of variance and Bonferroni post hoc testing (P < .05).', 'Approximately 88% of the TAP was retained in the root canal system regardless of the irrigation technique used (no difference among groups). Furthermore, approximately 50% of the radiolabeled TAP was present circumferentially up to 350 \u03bcm within the dentin. Conversely, up to 98% of the radiolabeled intracanal calcium hydroxide was removed, and most residual medicament was found present in the initial 50 \u03bcm of dentin.",
            "output": [
                "Do evaluation of triple antibiotic paste removal by different irrigation procedures?"
            ]
        },
        {
            "id": "task847-b9ed62fa3c324dc4829a5ff24afb238f",
            "input": "In Europe, extracts of Equisetum arvense (common horsetail) have a long tradition in the treatment of inflammatory disorders. To understand the molecular basis for its use, we investigated the immunomodulatory capacity of a standardized commercially available common horsetail extract on human primary lymphocyte function in vitro.', 'The standardized extract of Equisetum arvense was phytochemically characterized. Effects on proliferation, viability and activity of mitogen-activated human lymphocytes were assessed in comparison to cyclosporine A using annexin V/propidium iodide staining assays and flow cytometry-based surface receptor characterization, respectively. Intracellular levels of effector molecules (IL-2, IFN-\u03b3 and TNF-\u03b1) were analyzed with cytokine assays.', 'T cell proliferation was inhibited dose dependently by the Equisetum extract without induction of apoptosis or necrosis. This effect was mediated through inhibition of lymphocyte activation, specifically by diminishing CD69 and IL-2 surface receptor expression and intracellular IL-2 production. Furthermore, treatment with Equisetum arvense inhibited effector functions, as indicated by reduced production of IFN-\u03b3 and TNF-\u03b1.",
            "output": [
                "Does equisetum arvense ( common horsetail ) modulate the function of inflammatory immunocompetent cells?"
            ]
        },
        {
            "id": "task847-f92f28e293374a939d088c67717df1a8",
            "input": "To investigate the protective effects of remote ischemic postconditioning (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury.', 'Gastric IR was established in male Wistar rats by placing an elastic rubber band under a pressure of 290-310 mmHg on the proximal part of both lower limbs for 3 h followed by reperfusion for 0, 1, 3, 6, 12 or 24 h. RIP was performed using three cycles of 30 s of reperfusion and 30 s of reocclusion of the femoral aortic immediately after IR and before reperfusion for up to 24 h. Rats were randomly assigned to receive IR (n = 36), IR followed by RIP (n = 36), or sham treatment (n = 36). Gastric tissue samples were collected from six animals in each group at each timepoint and processed to determine levels of malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO). Additional samples were processed for histologic analysis by hematoxylin and eosin staining. Blood samples were similarly collected to determine serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor (TNF)-\u03b1 and interleukin (IL)-10.', 'The pathologic changes in gastric tissue induced by IR were observed by light microscopy. Administration of RIP dramatically reduced the gastric damage score after 6 h of reperfusion (5.85 \u00b1 0.22 vs 7.72 \u00b1 0.43; P < 0.01). In addition, RIP treatment decreased the serum activities of LDH (3.31 \u00b1 0.32 vs 6.46 \u00b1 0.03; P < 0.01), CK (1.94 \u00b1 0.20 vs 4.54 \u00b1 0.19; P < 0.01) and the concentration of TNF-\u03b1 (53.82 \u00b1 0.85 vs 88.50 \u00b1 3.08; P < 0.01), and elevated the concentration of IL-10 (101.46 \u00b1 5.08 vs 99.77 \u00b1 4.32; P < 0.01) induced by IR at 6 h. Furthermore, RIP treatment prevented the marked elevation in MDA (3.79 \u00b1 0.29 vs 6.39 \u00b1 0.81) content, XOD (7.81 \u00b1 0.75 vs 10.37 \u00b1 2.47) and MPO (0.47 \u00b1 0.05 vs 0.82 \u00b1 0.03) activities, and decrease in SOD (4.95 \u00b1 0.32 vs 3.41 \u00b1 0.38; P < 0.01) activity in the gastric tissue as measured at 6 h.",
            "output": [
                "Does remote ischemic postconditioning protect against gastric mucosal lesions in rats?"
            ]
        },
        {
            "id": "task847-2de73b88cc594b1a9e0bcdd8e3022f7a",
            "input": "The association between HIV and emphysema remains incompletely understood. We sought to determine whether HIV is an independent risk factor for emphysema severity and whether markers of HIV severity and systemic biomarkers of inflammation (IL-6), altered coagulation (D-dimer), and immune activation (soluble CD14) are associated with emphysema.', 'We performed a cross-sectional analysis of 114 participants with HIV infection and 89 participants without HIV infection in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study. Participants underwent chest CT imaging with blinded semiquantitative interpretation of emphysema severity, distribution, and type. We generated multivariable logistic regression models to determine the risk of HIV for radiographic emphysema, defined as > 10% lung involvement. Similar analyses examined associations of plasma biomarkers, HIV RNA, and recent and nadir CD4 cell counts with emphysema among participants with HIV infection.', 'Participants with HIV infection had greater radiographic emphysema severity with increased lower lung zone and diffuse involvement. HIV was associated with significantly increased risk for > 10% emphysema in analyses adjusted for cigarette smoking pack-years (OR, 2.24; 95% CI, 1.12-4.48). In multivariable analyses restricted to participants with HIV infection, nadir CD4 < 200 cells/\u03bcL (OR, 2.98; 95% CI, 1.14-7.81), and high soluble CD14 level (upper 25th percentile) (OR, 2.55; 95% CI, 1.04-6.22) were associated with increased risk of > 10% emphysema. IL-6 and D-dimer were not associated with emphysema in HIV.",
            "output": [
                "Is increased risk of radiographic emphysema in HIV associated with elevated soluble CD14 and nadir CD4?"
            ]
        },
        {
            "id": "task847-303e4469128b460f90ca760fdc3c8220",
            "input": "Knowledge about supportive care needs in patients with cutaneous invasive melanoma is scarce. We examined the unmet needs of melanoma patients treated with surgery and factors associated with these needs to assist health professionals identify areas needing clinical attention.', 'Cross-sectional multisite survey of UK patients ascertained 3 months to 5 years after complete resection of stage I-III cutaneous melanoma. Participants completed the following validated questionnaires: Supportive Care Needs Survey (SCNS-SF34 with melanoma module), Hospital Anxiety and Depression Scale and 51-item Functional Assessment of Cancer Therapy-Melanoma quality-of-life scale.', \"A total of 472 participants were recruited [319 (67%) clinical stage I-II). Mean age was 60 years (standard deviation = 14) and 255 (54%) were female. One hundred and twenty-three (27%) participants reported at least one unmet need (mostly 'low' level). The most frequently reported unmet needs were fears of cancer returning (n = 138, 29%), uncertainty about the future (n = 119, 25%), lack of information about risk of recurrence (n = 112, 24%) and about possible outcomes if melanoma were to spread (n = 91, 20%). One hundred and thirty-eight (29%) participants reported anxiety and 51 (11%) depression at clinical or subclinical levels. Patients with nodal disease had a significantly higher level of unmet supportive care needs (P < 0.001) as did patients with anxiety or depression (P < 0.001). Key correlates of the total SCNS-SF34 score for unmet supportive care needs were younger age (odds ratio, OR = 2.23, P < 0.001) and leaving school early (OR = 4.85, P < 0.001), while better emotional (OR = 0.89, P < 0.001) and social well-being (OR = 0.91, P < 0.001) were linked with fewer unmet needs. Neither patients' sex nor tumour thickness was associated with unmet needs.",
            "output": [
                "Does prevalence and correlate of unmet supportive care needs in patients with resected invasive cutaneous melanoma?"
            ]
        },
        {
            "id": "task847-28d5fef71aa04e5bb394e3e2abeda99f",
            "input": "The objective of this cross-sectional study was to characterize long-term breast pain in patients undergoing breast-conserving surgery and radiation (BCT) and to identify predictors of this pain.', 'We identified 355 eligible patients with Tis-T2N0M0 breast cancer who underwent BCT in 2007 to 2011, without recurrent disease. A questionnaire derived from the Late Effects Normal Tissue Task Force (LENT) Subjective, Objective, Management, Analytic (SOMA) scale was mailed with 7 items detailing the severity, frequency, duration, and impact of ipsilateral breast pain over the previous 2 weeks. A logistic regression model identified predictors of long-term breast pain based on questionnaire responses and patient, disease, and treatment characteristics.', 'The questionnaire response rate was 80% (n=285). One hundred thirty-five patients (47%) reported pain in the treated breast, with 19 (14%) having pain constantly or at least daily; 15 (11%) had intense pain. The pain interfered with daily activities in 11 patients (8%). Six patients (4%) took analgesics for breast pain. Fourteen (10%) thought that the pain affected their quality of life. On univariable analysis, volume of breast tissue treated to \u2265105% of the prescribed dose (odds ratio [OR] 1.001 per cc, 95% confidence interval [CI] 1.000-1.002; P=.045), volume treated to \u2265110% (OR 1.009 per cc, 95% CI 1.002-1.016; P=.012), hormone therapy use (OR 1.95, 95% CI 1.12-3.39; P=.02), and other sites of pain (OR 1.79, 95% CI 1.05-3.07; P=.03) predicted for long-term breast pain. On multivariable analysis, volume \u2265110% (OR 1.01 per cc, 95% CI 1.003-1.017; P=.007), shorter time since treatment (OR 0.98 per month, 95% CI 0.96-0.998; P=.03), and hormone therapy (OR 1.84, 95% CI 1.05-3.25; P=.03) were independent predictors of pain.",
            "output": [
                "Does dosimetric Inhomogeneity predict for Long-Term Breast Pain After Breast-Conserving Therapy?"
            ]
        },
        {
            "id": "task847-2939349786b74dbca78c7b84ce193e76",
            "input": "Venous stasis is a well-known risk factor for the development of venous thromboembolism. It is likely that stasis increases the risk of thrombosis by inducing hypercoagulability via the hypoxic procoagulant activation of endothelial and mononuclear cells and the accumulation of activated clotting factors. However, increased rates of thrombin formation have not been demonstrated in response to venous stasis in vivo.', 'In this study, we used the venous occlusion (VO) test to determine, if stasis triggers thrombin formation in healthy individuals (n=25) and patients with additional thrombotic risk factors, such as inherited thrombophilia (n=19) and symptomatic atherosclerosis (n=15). Thrombin formation was monitored by measuring plasma levels of free thrombin using a highly sensitive oligonucleotide enzyme capture assay (OECA) in addition to the plasma levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin-complexes (TAT). The plasma levels of activated protein C (APC) were additionally measured using an APC-OECA.', 'VO induced a significant (p<0.05) increase in the levels of tissue-type plasminogen activator and plasmin-\u03b12-antiplasmin-complexes. In all three cohorts, the majority of samples obtained during VO showed no quantifiable thrombin or APC levels. Consistent with these findings F1+2 and TAT did not change.",
            "output": [
                "Does short-term venous stasis induce fibrinolytic activation but not thrombin formation?"
            ]
        },
        {
            "id": "task847-00c248888bcc450d86314d30337ad890",
            "input": "Population studies have shown obesity and diabetes to be risk factors for atherosclerosis. We assessed changes in the common carotid arteries in rat models of obesity and diabetes without hypertension.', 'Twenty 30-week-old male spontaneously diabetic and obese model Otsuka Long-Evans Tokushima Fatty (OLETF) and 20 control Long-Evans Tokushima Otsuka (LETO) rats were used in the experiments. The animals were considered diabetic if the plasma glucose level peaked at >300 mg/dL and remained at >200 mg/dL for 120 minutes. Blood gas physiological parameters were continuously monitored under anesthesia, and the flow of the carotid artery was assessed with ultrasonography. All animals were sacrificed with an overdose of anesthesia at the end of the experiment. Sections of the middle portion of the internal carotid artery were cut and stained with hematoxylin and eosin to assess the overall morphology.', 'All OLETF rats were diabetic, and all LETO rats were non-diabetic. The physiological parameters did not differ significantly between the control and model rats, whereas the carotid artery wall thickness (19.3 \u00b1 3.2 vs. 6.1 \u00b1 4.5 \u03bcm) was significantly different between the two groups. The blood flow velocity in the common carotid artery determined using ultrasonography and color Doppler sonography was significantly increased during systole in the model rats compared with that observed in the control rats (203 \u00b1 20.3 vs. 55.3 \u00b1 21.4 cm/sec).",
            "output": [
                "Is carotid artery stenosis exacerbated in spontaneously obese model rats with diabetes?"
            ]
        },
        {
            "id": "task847-bf70d9bc81914a2c91f697b94261c2f6",
            "input": "Central core disease is a congenital myopathy, characterized by presence of central core-like areas in muscle fibers. Patients have mild or moderate weakness, hypotonia and motor developmental delay. The disease is caused by mutations in the human ryanodine receptor gene (RYR1), which encodes a calcium-release channel. Since the RYR1 gene is huge, containing 106 exons, mutation screening has been limited to three 'hot spots', with particular attention to the C-terminal region. Recent next-generation sequencing methods are now identifying multiple numbers of variants in patients, in which interpretation and phenotype prevision is difficult.\", \"In a Brazilian Caucasian family, clinical, histopathological and molecular analysis identified a new case of central core disease in a 48-year female. Sanger sequencing of the C-terminal region of the RYR1 gene identified two different missense mutations: c.14256 A >\\u2009C polymorphism in exon 98 and c.14693 T >\\u2009C in exon 102, which have already been described as pathogenic. Trans-position of the 2 mutations was confirmed because patient's daughter, mother and sister carried only the exon 98's mutation, a synonymous variant that was subsequently found in the frequency of 013-0,05 of alleles. Further next generation sequencing study of the whole RYR1 gene in the patient revealed the presence of additional 5 common silent polymorphisms in homozygosis and 8 polymorphisms in heterozygosis.",
            "output": [
                "Do silent polymorphisms in the RYR1 gene modify the phenotype of the p.4898 I > T pathogenic mutation in central core disease : a case report?"
            ]
        },
        {
            "id": "task847-442b2c411c8e4ede8f7c42c837861bc2",
            "input": "Flavonoids, which have been identified in a variety of plants, have been demonstrated to elicit beneficial effects on memory. Some studies have reported that flavonoids derived from Erythrina plants can provide such beneficial effects on memory. The aim of this study was to identify the flavonoids present in the stem bark crude extract of Erythrina falcata (CE) and to perform a bioactivity-guided study on conditioned fear memory.', 'The secondary metabolites of CE were identified by high performance liquid chromatography combined with a diode array detector, electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI/MSn) and nuclear magnetic resonance (NMR). The buthanolic fraction (BuF) was obtained by partitioning. Subfractions from BuF (BuF1 - BuF6) and fraction flavonoidic (FfA and FfB) were obtained by flash chromatography. The BuF3 and BuF4 fractions were used for the isolation of flavonoids, which was performed using HPLC-PAD. The isolated substances were quantified by HPLC-DAD and their structures were confirmed by nuclear magnetic resonance (NMR). The activities of CE and the subfractions were monitored using a one-trial, step-down inhibitory avoidance (IA) task to identify the effects of these substances on the acquisition and extinction of conditioned fear in rats.', 'Six subclasses of flavonoids were identified for the first time in CE. According to our behavioral data, CE, BuF, BuF3 and BuF4, the flavonoidic fractions, vitexin, isovitexin and 6-C-glycoside-diosmetin improved the acquisition of fear memory. Rats treated with BuF, BuF3 and BuF4 were particularly resistant to extinction. Nevertheless, rats treated with FfA and FfB, vitexin, isovitexin and 6-C-glycoside-diosmetin exhibited gradual reduction in conditioned fear response during the extinction retest session, which was measured at 48 to 480 h after conditioning.",
            "output": [
                "Are flavones from Erythrina falcata modulators of fear memory?"
            ]
        },
        {
            "id": "task847-c48cef0d29d2471db54a3dd2bb566fd2",
            "input": "Wee1-like kinase (Wee1) is a tyrosine kinase which negatively regulates entry into mitosis at the G2 to M-phase transition and has a role in inhibition of unscheduled DNA replication in S-phase. The present study investigated the clinical role of Wee1 in advanced-stage (FIGO III-IV) ovarian serous carcinoma.', 'Wee1 protein expression was analyzed in 287 effusions using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including survival. Forty-five effusions were additionally studied using Western blotting. Wee1 was further silenced in SKOV3 and OVCAR8 cells by siRNA knockdown and proliferation was assessed.', 'Nuclear expression of Wee1 in tumor cells was observed in 265/287 (92%) and 45/45 (100%) effusions by immunohistochemistry and Western blotting, respectively. Wee1 expression by immunohistochemistry was significantly higher in post-chemotherapy disease recurrence compared to pre-chemotherapy effusions obtained at diagnosis (p=0.002). Wee1 silencing in SKOV3 and OVCAR8 cells reduced proliferation. In univariate survival analysis of the entire cohort, a trend was observed between high (>25% of cells) Wee1 expression and poor overall survival (p=0.083). Survival analysis for 109 patients with post-chemotherapy effusions showed significant association between Wee1 expression and poor overall survival (p=0.004), a finding which retained its independent prognostic role in Cox multivariate analysis (p=0.003).",
            "output": [
                "Is wee1 a novel independent prognostic marker of poor survival in post-chemotherapy ovarian carcinoma effusions?"
            ]
        },
        {
            "id": "task847-ce6a051347a54574bfa7d85613b6aaf6",
            "input": "Liver ischemia reperfusion (I/R) injury is a common pathophysiological process in many clinical settings. Carvacrol, a food additive commonly used in essential oils, has displayed antimicrobials, antitumor and antidepressant-like activities. In the present study, we investigated the protective effects of carvacrol on I/R injury in the Wistar rat livers and an in vitro hypoxia/restoration (H/R) model.', 'The hepatoportal vein, hepatic arterial and hepatic duct of Wistar rats were isolated and clamped for 30 min, followed by a 2 h reperfusion. Buffalo rat liver (BRL) cells were incubated under hypoxia for 4 h, followed normoxic conditions for 10 h to establish the H/R model in vitro. Liver injury was evaluated by measuring serum levels of alanine aminotransferase (ALT) and aspatate aminotransferase (AST), and hepatic levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondiadehyde (MDA), and hepatic histology and TUNEL staining. MTT assay, flow cytometric analysis and Hoechst 33258 staining were used to evaluate the proliferation and apoptosis of BRL cells in vitro. Protein expression was examined by Western Blot analysis.', 'Carvacrol protected against I/R-induced liver damage, evidenced by significantly reducing the serum levels of ALT and AST, histological alterations and apoptosis of liver cells in I/R rats. Carvacrol exhibited anti-oxidative activity in the I/R rats, reflected by significantly reducing the activity of SOD and the content of MDA, and restoring the activity of CAT and the content of GSH, in I/R rats. In the in vitro assays, carvacrol restored the viability and inhibited the apoptosis of BRL cells, which were subjected to a mimic I/R injury induced by hypoxia. In the investigation on molecular mechanisms, carvacrol downregulated the expression of Bax and upregulated the expression of Bcl-2, thus inhibited the activation of caspase-3. Carvacrol was also shown to enhance the phosphorylation of Akt.",
            "output": [
                "Does carvacrol alleviate ischemia reperfusion injury by regulating the PI3K-Akt pathway in rats?"
            ]
        },
        {
            "id": "task847-48000db4a0a146c095d7a51537fd227c",
            "input": "Chikungunya virus causes chronic infection with manifestations of joint pain. Human synovial fibroblasts get infected with CHIKV and could lead to pro-inflammatory responses. MicroRNAs have potentials to regulate the gene expression of various anti-viral and pro-inflammatory genes. The study aims to investigate the role of miR-146a in modulation of inflammatory responses of human synovial fibroblasts by Chikungunya virus.', 'To study the role of miR-146a in CHIKV pathogenesis in human synovial cells and underlying inflammatory manifestations, we performed CHIKV infection in primary human synovial fibroblasts. Western blotting, real-time PCR, luciferase reporter assay, overexpression and knockdown of cellular miR-146a strategies have been employed to validate the role of miR-146a in regulation of pro-inflammatory NF-\u03baB pathway.', 'CHIKV infection induced the expression of cellular miR-146a, which resulted into down-regulation of TRAF6, IRAK1, IRAK2 and increased replication of CHIKV in human synovial fibroblasts. Exogenous expression of miR-146a in human synovial fibroblasts led to decreased expression of TRAF6, IRAK1, IRAK2 and decreased replication of CHIKV. Inhibition of cellular miR-146a by anti-miR-146a restored the expression levels of TRAF6, IRAK1 and IRAK2. Downregulation of TRAF6, IRAK1 and IRAK2 led to downstream decreased NF-\u03baB activation through negative feedback loop.",
            "output": [
                "Does chikungunya virus exploit miR-146a to regulate NF-\u03baB pathway in human synovial fibroblasts?"
            ]
        },
        {
            "id": "task847-2ea731a80067439bb6754bd3c2c4dfc7",
            "input": "Mitochondrial permeability transition pore (mPTP) opening is a terminal event leading to mitochondrial dysfunction and cell death under conditions of oxidative stress (OS). However, mPTP blockade with cyclosporine A (CsA) has shown variable efficacy in limiting post-ischemic dysfunction and arrhythmias. We hypothesized that strong feedback between energy dissipating (mPTP) and cardioprotective (mKATP) channels determine vulnerability to OS.', 'Guinea pig hearts (N = 61) were challenged with H2O2 (200 \u03bcM) to elicit mitochondrial membrane potential (\u0394\u03a8m) depolarization. High-resolution optical mapping was used to measure \u0394\u03a8m or action potentials (AP) across the intact heart. Hearts were treated with CsA (0.1 \u03bcM) under conditions that altered the activity of mKATP channels either directly or indirectly via its regulation by protein kinase C. mPTP blockade with CsA markedly blunted (P < 0.01) OS-induced \u0394\u03a8m depolarization and delayed loss of LV pressure (LVP), but did not affect arrhythmia propensity. Surprisingly, prevention of mKATP activation with the chemical phosphatase BDM reversed the protective effect of CsA, paradoxically exacerbating OS-induced \u0394\u03a8m depolarization and accelerating arrhythmia onset in CsA treated compared to untreated hearts (P < 0.05). To elucidate the putative molecular mechanisms, mPTP inhibition by CsA was tested during conditions of selective PKC inhibition or direct mKATP channel activation or blockade. Similar to BDM, the specific PKC inhibitor, CHE (10 \u03bcM) did not alter OS-induced \u0394\u03a8m depolarization directly. However, it completely abrogated CsA-mediated protection against OS. Direct pharmacological blockade of mKATP, a mitochondrial target of PKC signaling, equally abolished the protective effect of CsA on \u0394\u03a8m depolarization, whereas channel activation with 30 \u03bcM Diazoxide protected against \u0394\u03a8m depolarization (P < 0.0001). Conditions that prevented mKATP activation either directly or indirectly via PKC inhibition led to accelerated \u0394\u03a8m depolarization and early onset of VF in response to OS. Investigation of the electrophysiological substrate revealed accelerated APD shortening in response to OS in arrhythmia-prone hearts.",
            "output": [
                "Do functional crosstalk between the mitochondrial PTP and KATP channels determine arrhythmic vulnerability to oxidative stress?"
            ]
        },
        {
            "id": "task847-47fdfa89147d495ca084e647351ba875",
            "input": "The effect of in vitro expansion of human adipose-derived stem cells (ASCs) on stem cell properties is controversial. We examined serial subcultivation with expansion on the ability of ASCs to grow and differentiate into osteoblastic lineages.', 'Flow cytometric analysis, growth kinetics, cell population doubling time, light microscopy and confocal analysis, and osteogenesis induction were performed to assess growth and osteogenic potential of subcultivated ASCs at passages 2 (P2), P4 and P6.', 'Flow cytometric analysis revealed that ASCs at P2 express classical mesenchymal stem cell markers including CD44, CD73, and CD105, but not CD14, CD19, CD34, CD45, or HLA-DR. Calcium deposition and alkaline phosphatase activity were the highest at P2 but completely abrogated at P4. Increased passage number impaired cell growth; P2 cultures exhibited exponential growth, while cells at P4 and P6 showed near linear growth with cell population doubling times increased from 3.2 at P2 to 4.8\\xa0d at P6. Morphologically, cells in various subcultivation stages showed flattened shape at low density but spindle-like structures at confluency as judged by phalloidin staining.",
            "output": [
                "Are proliferation and differentiation of human adipose-derived mesenchymal stem cells ( ASCs ) into osteoblastic lineage passage dependent?"
            ]
        },
        {
            "id": "task847-3a3b99b0758d47aaac060fde887a4b04",
            "input": "Intestinal inflammation is often associated with an increased level of serotonin (5-HT), an important gastrointestinal signaling molecule involved in gut homeostasis through stimulation of specific receptors. In this study, we investigated the role of 5-HT7 receptor (5-HT7R) in the induction and development of intestinal inflammation using a mouse model of acute and chronic colitis and human patients with Crohn's disease (CD).\", 'Acute colitis was induced through administration of dextran sodium sulfate to wild-type, 5-HT7R-deficient mice and hematopoietic bone marrow chimera. Chronic colitis was induced in interleukin 10-deficient mice. The role of 5-HT7R in gut inflammation was assessed using agonist/antagonist treatment. We investigated expression and distribution of 5-HT7R, extent of gut inflammation with magnetic resonance imaging and histological analysis, survival rate, and disease activity index. Finally, biopsies from the large intestine of patients with CD were analyzed.', 'Under basal conditions, 5-HT7R is expressed both in enteric neurons and CD11c cells of the large intestine. Expression of 5-HT7R significantly increased after induction of colitis in mice and in inflamed intestinal regions of patients with CD in CD11c/CD86 double-positive cells. Pharmacological blockade or genetic ablation of 5-HT7R resulted in increased severity of both acute and chronic dextran sodium sulfate-induced colitis, whereas receptor stimulation showed an anti-inflammatory effect. Analysis of bone marrow chimera indicated importance of 5-HT7R expressed by hematopoietic cells in intestinal inflammation.",
            "output": [
                "Is serotonin 5-HT7 receptor critically involved in acute and chronic inflammation of the gastrointestinal tract?"
            ]
        },
        {
            "id": "task847-45d56cfdbb9942b4806d825814e614f3",
            "input": "Platelet-derived growth factor-BB (PDGF-BB) has been implicated in the proliferation, migration and synthetic activities of smooth muscle cells that characterize physiologic and pathologic tissue remodeling in hollow organs. However, neither the molecular basis of PDGFR-regulated signaling webs, nor the extent to which specific components within these networks could be exploited for therapeutic benefit has been fully elucidated.', 'Expression profiling and quantitative proteomics analysis of PDGF-treated primary human bladder smooth muscle cells identified 1,695 genes and 241 proteins as differentially expressed versus non-treated cells. Analysis of gene expression data revealed MYC, JUN, EGR1, MYB, RUNX1, as the transcription factors most significantly networked with up-regulated genes. Forty targets were significantly altered at both the mRNA and protein levels. Proliferation, migration and angiogenesis were the biological processes most significantly associated with this signature, and MYC was the most highly networked master regulator. Alterations in master regulators and gene targets were validated in PDGF-stimulated smooth muscle cells in vitro and in a model of bladder injury in vivo. Pharmacologic inhibition of MYC and JUN confirmed their role in SMC proliferation and migration. Network analysis identified the diaphanous-related formin 3 as a novel PDGF target regulated by MYC and JUN, which was necessary for PDGF-stimulated lamellipodium formation.",
            "output": [
                "Does integration of proteomic and transcriptomic profiles identify a novel PDGF-MYC network in human smooth muscle cells?"
            ]
        },
        {
            "id": "task847-e932575496544e0391832e9e9cd6247d",
            "input": "Dairy foods help achieve essential nutrient adequacy. This role may be conflicted where so-called chronic diseases prevail. We have examined associations between dairy intake and mortality where dairy foods have not been traditional.', 'A representative Taiwanese cohort of 3810 subjects, aged 19-64 years, derived from the Nutrition and Health Survey in Taiwan (NAHSIT, 1993-1996) was linked to death registration (1993-2008). Participants were categorized by 4 dairy weekly intake frequencies from 0 to >7 times. Mortality hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional-hazards models.', 'Nonconsumers of dairy products included 30.7% of the men and 22.1% of the women. Adverse sociodemographic and personal behaviors were generally significantly associated with lower dairy consumption. After adjustment for covariates, together with body mass index (BMI) and supplement use, those with 3-7 times/week intakes had an HR (95% CI) for all-cause mortality of 0.61 (0.39-0.96) with a significant dose-response trend (p = 0.043). Similarly, the HR for cardiovascular disease (CVD) mortality with dairy weekly intake frequency >7 was 0.14 (0.02-0.97) with a significant linear trend (p = 0.007). For stroke, the corresponding HR (95% CI) was 0.03 (0.00-0.28) with a linear trend. By age and with adjustment for dietary quality, food, and calcium or vitamin D intake, significance and dose-response relationships remained. Dairy intake and cancer mortality were not associated.",
            "output": [
                "Is optimal dairy intake predicated on total , cardiovascular , and stroke mortalities in a Taiwanese cohort?"
            ]
        },
        {
            "id": "task847-64c8d179c5674c6f8cb424b008641c44",
            "input": "The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer.', 'Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used.', 'All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98%), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22% of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100%). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients.",
            "output": [
                "Does intraoperative 3-D imaging improve sentinel lymph node biopsy in oral cancer?"
            ]
        },
        {
            "id": "task847-e49e4be99def401d84c11ee3376ed08c",
            "input": "The main aim was to compare robotic gait training vs. balance training for reducing postural instability in patients with Parkinson's disease. The secondary aim was to compare their effects on the level of confidence during activities of daily living requiring balance, functional mobility and severity of disease.\", 'Randomized controlled trial.', 'University hospital.', \"A total of 66 patients with Parkinson's disease at Hoehn and Yahr Stage 3.\", 'After balanced randomization, all patients received 12, 45-minute treatment sessions, three days a week, for four consecutive weeks. A group underwent robot-assisted gait training with progressive gait speed increasing and body-weight support decreasing. The other group underwent balance training aimed at improving postural reactions (self and externally induced destabilization, coordination, locomotor dexterity exercises).', 'Patients were evaluated before, after and one month posttreatment.', 'Berg Balance Scale.', \"Activities-Specific Balance Confidence Scale; Timed Up and Go Test; Unified Parkinson's Disease Rating Scale.\", 'No significant differences were found between the groups for the Berg Balance Scale either immediately after intervention (mean score in the robotic training group 51.58 \u00b13.94; mean score in the balance training group 51.15 \u00b13.46), or one-month follow-up (mean score in the robotic training group 51.03 \u00b14.63; mean score in the balance training group 50.97 \u00b14.28). Similar results were found for all the secondary outcome measures.",
            "output": [
                "Is robot-assisted gait training superior to balance training for improving postural instability in patients with mild to moderate Parkinson 's disease : a single-blind randomized controlled trial?"
            ]
        },
        {
            "id": "task847-84c895935e34471bb3b9b4930c35a24c",
            "input": "The aim of this study was to analyze the effects of dual tasking on obstacle crossing during walking by individuals with Alzheimer's disease (AD) and by healthy older people.\", 'Thirty four elderly individuals (16 healthy subjects and 18 individuals with AD) were recruited to participate in this study. Three AD individuals and one control participant were excluded due to exclusion criteria. The participants were instructed to walk barefoot at their own speed along an 8 m long pathway. Each participant performed five trials for each condition (unobstructed walking, unobstructed walking with dual tasking, and obstacle crossing during walking with dual tasking). The trials were completely randomized for each participant. The mid-pathway stride was measured in the unobstructed walking trials and the stride that occurred during the obstacle avoidance was measured in the trials that involved obstacle crossing.",
            "output": [
                "Is obstacle crossing with dual tasking a danger for individuals with Alzheimer 's disease and for healthy older people?"
            ]
        },
        {
            "id": "task847-57b2fd93cdca46d483620e6ad2821db1",
            "input": "Advances in digital imaging methods have resulted in use of telecytology in the immediate assessment of fine-needle aspiration (FNA) specimens. We retrospectively compared the nondiagnostic rate for endoscopic ultrasound-guided (EUS) FNA of pancreatic lesions in two groups: one with on-site evaluation for adequacy via telecytopathology and the other without on-site adequacy evaluation.', 'All patients undergoing EUS-FNA of pancreatic lesions over a 2-year period were included. Direct smears were immediately wet-fixed or air-dried, and any residual material was rinsed in saline for cell block or cytospin preparation. Patients were divided into two groups: Group 1 had on-site telecytopathology evaluation for adequacy by a cytopathologist, and Group 2 had no on-site adequacy evaluation. The cytologic diagnoses were reviewed, and the nondiagnostic rates for each group were calculated. The age, sex, and characteristics of pancreatic lesions (solid versus cystic) between the two groups were compared.', 'In total, 217 patients were included. Telecytopathology on-site evaluation was provided for 95 (43.8%) cases. There was no difference between the groups in terms of age and sex. Pancreatic lesions were predominantly solid in the group that underwent telecytopathology on-site evaluation (p<0.005). The nondiagnostic rates for solid lesions in Group 1 and Group 2 were 3.7% and 25.6%, respectively (p<0.0001). Although the nondiagnostic rate for cystic lesion was higher in Group 2, it did not reach a level of statistical significance (16.5% versus 7.1%; p=0.249). After adjusting for the effects of sex and lesion characteristics (solid versus cystic lesion) with multivariate logistic regression, the odds of having a nondiagnostic specimen in Group 2 was 6.9 times greater than in Group 1, and the result was statistically significant (p=0.0013).",
            "output": [
                "Does telecytopathology for on-site adequacy evaluation decrease the nondiagnostic rate in endoscopic ultrasound-guided fine-needle aspiration of pancreatic lesions?"
            ]
        },
        {
            "id": "task847-d45a852ae62d443a895bd6b204af1da2",
            "input": "Serum KL-6 is a useful biomarker for the diagnosis of interstitial lung diseases (ILD). However, KL-6 has not been used to discriminate different types of ILD. Serum KL-6 concentrations can vary depending on antigen exposure levels in patients with hypersensitivity pneumonitis (HP); however, seasonal changes in serum KL-6 concentrations in ILD have not been determined. We hypothesized that seasonal variation of serum KL-6 is greater in HP than for the other ILD. The aim of this study was to determine seasonal variation of serum KL-6 concentrations in various ILD.', 'Serum KL-6 concentrations in the summer season from June 1 to September 30 and the winter season from November 1 to February 28 were retrospectively analyzed in patients with idiopathic pulmonary fibrosis (IPF, n=16), non-specific interstitial pneumonia (NSIP, n=16), collagen vascular disease-associated interstitial pneumonia (CVD-IP, n=33), house-related HP (House-HP, n=9), bird-related HP (Bird-HP, n=9), and combined pulmonary fibrosis and emphysema (CPFE, n=13).', 'Bird-HP and House-HP showed greater seasonal serum KL-6 variation than the other ILD. Serum KL-6 concentrations in Bird-HP were significantly increased in the winter and KL-6 concentrations in House-HP were significantly increased in the summer. Serum KL-6 variation was significantly greater in acute HP than chronic HP. Receiver operating characteristic curve analysis revealed that greater seasonal variation in serum KL-6 concentrations is diagnostic for Bird-HP.",
            "output": [
                "Is seasonal variation of serum KL-6 concentrations greater in patients with hypersensitivity pneumonitis?"
            ]
        },
        {
            "id": "task847-075c7652e4ed4bd6a32396da3457a69c",
            "input": "EEG and somatosensory evoked potential are highly predictive of poor outcome after cardiac arrest; their accuracy for good recovery is however low. We evaluated whether addition of an automated mismatch negativity-based auditory discrimination paradigm (ADP) to EEG and somatosensory evoked potential improves prediction of awakening.', 'EEG and ADP were prospectively recorded in 30 adults during therapeutic hypothermia and in normothermia. We studied the progression of auditory discrimination on single-trial multivariate analyses from therapeutic hypothermia to normothermia, and its correlation to outcome at 3 months, assessed with cerebral performance categories.', 'At 3 months, 18 of 30 patients (60%) survived; 5 had severe neurologic impairment (cerebral performance categories = 3) and 13 had good recovery (cerebral performance categories = 1-2). All 10 subjects showing improvements of auditory discrimination from therapeutic hypothermia to normothermia regained consciousness: ADP was 100% predictive for awakening. The addition of ADP significantly improved mortality prediction (area under the curve, 0.77 for standard model including clinical examination, EEG, somatosensory evoked potential, versus 0.86 after adding ADP, P = 0.02).",
            "output": [
                "Does automated auditory mismatch negativity paradigm improve coma prognostic accuracy after cardiac arrest and therapeutic hypothermia?"
            ]
        },
        {
            "id": "task847-e79224f682464faa84a8432fdfc95dc6",
            "input": "Manual scoring of sleep relies on identifying certain characteristics in polysomnograph (PSG) signals. However, these characteristics are disrupted in patients with neurodegenerative diseases.', \"This study evaluates sleep using a topic modeling and unsupervised learning approach to identify sleep topics directly from electroencephalography (EEG) and electrooculography (EOG). PSG data from control subjects were used to develop an EOG and an EEG topic model. The models were applied to PSG data from 23 control subjects, 25 patients with periodic leg movements (PLMs), 31 patients with idiopathic REM sleep behavior disorder (iRBD) and 36 patients with Parkinson's disease (PD). The data were divided into training and validation datasets and features reflecting EEG and EOG characteristics based on topics were computed. The most discriminative feature subset for separating iRBD/PD and PLM/controls was estimated using a Lasso-regularized regression model.\", 'The features with highest discriminability were the number and stability of EEG topics linked to REM and N3, respectively. Validation of the model indicated a sensitivity of 91.4% and a specificity of 68.8% when classifying iRBD/PD patients.",
            "output": [
                "Does data-driven modeling of sleep EEG and EOG reveal characteristics indicative of pre-Parkinson 's and Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-9ef5b9e143da450f8169b5fee3d1317e",
            "input": "To find permanent prostate implant (PPI) pre-plan dosimetric parameters that predict post-implant D90 \u2265 140 Gy.', 'Pre-plans were evaluated for 504 patients undergoing PPI with (125)I seeds for low or intermediate risk prostate cancer. Baseline patient and disease factors, numbers of seeds, ratios of number of seeds to available positions (occupancy proportion), and distances between the 100% isodose line and edge of the prostate (margin) planned for the whole prostate (WP), superior (S), inferior (I), anterior (A), and posterior (P) halves, SA, SP, IA, and IP quarters, and superior (ST), inferior (IT), and middle (MT) thirds, and anterior (AT) and posterior (PT) middle one-sixth segments were analyzed by post-implant D90 subset (\u2265 140 Gy vs. < 140 Gy).', '20% had post-implant D90 < 140 Gy (mean: 128.0 Gy, range: 97.5-139.2) vs. \u2265 140 Gy (mean: 154.4 Gy, range: 140.0-193.5). The D90 \u2265 140 Gy subset had larger AT and IA segment mean numbers of seeds (p = 0.01, 0.046), larger WP, S, A, SA, ST, AT, and MT segment mean margins (p = 0.01, 0.01, 0.001, 0.0001, 0.03, 0.005, 0.02), and lower PT segment occupancy proportion (p = 0.004). On multivariate analysis, independent predictors of post-implant D90 \u2265 140 Gy were increased SA mean margin, no pre-implant 5-\u03b1-reductase inhibitor, higher pre-plan D90, decreased P occupancy proportion, no pre-implant hormone therapy, and decreased SP mean margin.",
            "output": [
                "Do pre-plan parameters predict post-implant D90 \u2265 140 Gy for ( 125 ) I permanent prostate implants?"
            ]
        },
        {
            "id": "task847-6d06353cbb8c4192987df3f1dac840b3",
            "input": "Parkinson's disease (PD) is the second most common neurodegenerative movement disorder, caused by preferential dopaminergic neuronal cell death in the substantia nigra, a process also influenced by oxidative stress. L-3,4-dihydroxyphenylalanine (L-DOPA) represents the main treatment route for motor symptoms associated with PD however, its exact mode of action remains unclear. A spectrum of conflicting data suggests that L-DOPA may damage dopaminergic neurons due to oxidative stress whilst other data suggest that L-DOPA itself may induce low levels of oxidative stress, which in turn stimulates endogenous antioxidant mechanisms and neuroprotection.\", 'In this study we performed a two-dimensional gel electrophoresis (2DE)-based proteomic study to gain further insight into the mechanism by which L-DOPA can influence the toxic effects of H2O2 in neuronal cells. We observed that oxidative stress affects metabolic pathways as well as cytoskeletal integrity and that neuronal cells respond to oxidative conditions by enhancing numerous survival pathways. Our study underlines the complex nature of L-DOPA in PD and sheds light on the interplay between oxidative stress and L-DOPA.",
            "output": [
                "Does proteome analysis reveal roles of L-DOPA in response to oxidative stress in neurons?"
            ]
        },
        {
            "id": "task847-03e10fa965ec4c84a2afe1664718cb34",
            "input": "The optimal timing of surgery for multiply injured patients with operative spinal injuries remains unknown. The purported benefits of early intervention must be weighed against the morbidity of surgery in the early post-injury period. The performance of spine surgery in the Afghanistan theater permits analysis of the morbidity of early surgery on military casualties. The objective is to compare surgical morbidity of early spinal surgery in multiply injured patients versus stable patients.', 'Patients were retrospectively categorized as stable or borderline unstable depending on the presence of at least one of the following: ISS >40, ISS >20 and chest injury, exploratory laparotomy or thoracotomy, lactate >2.5 mEq/L, platelet <110,000/mm(3), or >10 U PRBCs transfused pre-operatively. Surgical morbidity, complications, and neurologic improvement between the two groups were compared retrospectively.', '30 casualties underwent 31 spine surgeries during a 12-month period. 16 of 30 patients met criteria indicating a borderline unstable patient. Although there were no significant differences in the procedures performed for stable and borderline unstable patients as measured by the Surgical Invasiveness Index (7.5 vs. 6.9, p = 0.8), borderline unstable patients had significantly higher operative time (4.3 vs. 3.0 h, p = 0.01), blood loss (1,372 vs. 366 mL, p = 0.001), PRBCs transfused intra-op (3.88 vs. 0.14 U, p < 0.001), and total PRBCs transfused in theater (10.18 vs. 0.31 U, p < 0.001).",
            "output": [
                "Do morbidity of early spine surgery in the multiply injured patient?"
            ]
        },
        {
            "id": "task847-25d4c04418634f4a97de5b2a2819cc09",
            "input": "Lipopolysaccharide (LPS) is considered a prominent pathogenic factor in inflammatory bone diseases. LPS challenge contributes to the production of reactive oxygen species (ROS) in diverse inflammatory diseases. However, its mechanism remains to be clarified in bone. Thus, we investigated the critical mechanism of ROS in LPS-induced osteoclastogenesis and bone loss.', 'Antioxidant prevented LPS-induced osteoclast formation via inhibition of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and c-Fos expression in preosteoclasts. Moreover, LPS-induced osteoclast formation via ROS was attenuated by treatment with c-Jun N-terminal protein kinase (JNK) inhibitor. Interestingly, LPS also activated signal transducer and activator of transcription 3 (STAT3), which is suppressed by antioxidants. We found that knockdown of STAT3 or use of a STAT3 inhibitor resulted in a significant reduction in interleukin-1 beta (IL-1\u03b2), interleukin-6 (IL-6), and nitric oxide (NO) production, followed by decreased osteoclast formation by LPS. Peroxiredoxin II (PrxII) is a member of the antioxidant enzyme family, and it plays a protective role against oxidative damage caused by ROS. In our study, ROS production and osteoclast formation by LPS was significantly enhanced in PrxII(-/-) cells. Moreover, JNK-mediated c-Fos and NFATc1 expression was promoted in PrxII(-/-) cells. Furthermore, STAT3 activation and accompanying IL-1\u03b2, IL-6, and NO production was also increased in PrxII(-/-) cells. Consistent with the in vitro result, PrxII-deficient mice showed increased osteoclast formation and bone loss by LPS challenge compared with wild-type mice.', 'For the first time, we showed that LPS-induced ROS signaling is dependent on the coordinated mechanism of JNK and STAT3 during osteoclastogenesis, which is negatively regulated by PrxII.",
            "output": [
                "Does peroxiredoxin II negatively regulate lipopolysaccharide-induced osteoclast formation and bone loss via JNK and STAT3?"
            ]
        },
        {
            "id": "task847-8457967851854640a2ca12947a7f6744",
            "input": "Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite being considered as a chemosensitive disease, the real impact of perioperative chemotherapy on metastasis-free survival (MFS) is controversial. We have shown that metastatic relapse of SS is strongly associated with genomic complexity. There are no data regarding the potential correlation between genomic complexity and response to chemotherapy.', 'The study population included 65 SS patients diagnosed between 1991 and 2013 and with available tissue material. Genomic profiling was carried out by using array-CGH. Forty-five SS out of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy. Radiological response was assessed according to RECIST criteria. Histological response was defined by the percentage of recognizable tumor cells on the surgical specimen.', 'Genomic complexity was significantly associated with MFS. However, there was no statistically significant association between radiological or histological response and genomic complexity.",
            "output": [
                "Is response to chemotherapy related to chromosome instability in synovial sarcoma?"
            ]
        },
        {
            "id": "task847-3319bd1540eb4b6bacb84be6a5690ebc",
            "input": "Studies on the role of labour market position and change in alcohol use during midlife are scarce and their results are inconclusive mainly due to their failure to define comprehensive and distinct labour market groups and the short periods of time studied. In this study we used different activity categories for men and women to examine alcohol use trajectories in midlife covering a period of 17\\u2005years.', 'Using data from four sweeps of the National Child Development Study covering ages 33-50 (N=9960), we used multilevel growth models to study the association between labour market categories and longitudinal changes in weekly units of alcohol consumed.', \"In the reference group of full-time employed men alcohol trajectory decreased over the follow-up period (\u03b2=-0.14; 95% CI -0.18 to -0.11) while in the reference group of employed women it increased (\u03b2=0.06; 95% CI 0.04 to 0.08). Men and women who were 'mainly sick' had significantly steeper declines in their alcohol consumption trajectory. Women who became employed after being homemakers had the steepest increase in alcohol use (\u03b2=0.05; 95% CI 0.01 to 0.09).",
            "output": [
                "Do the relationship between labour market categories and alcohol use trajectories in midlife?"
            ]
        },
        {
            "id": "task847-123c13fe360a42f69042c37f3712e4e4",
            "input": "The non-neuronal acetylcholine system (NNAS) in endothelial cells participates in modulating endothelial function, vascular tone, angiogenesis and inflammation, thus plays a critical role in cardiovascular diseases. In this study, we used a proteomic approach to study potential downstream receptor-effectors of NNAS that were involved in regulating cellular function in endothelial cells.', 'Human umbilical vein endothelial cells were incubated in the presence of acetylcholine, oxotremorine, pilocarpine or nicotine at the concentration of 10 \u03bcmol/L for 12 h, and the expressed proteins in the cells were separated and identified with two-dimensional electrophoresis (2-DE) and LC-MS. The protein spots with the largest changes were identified by LC-MS. Biowork software was used for database search of the peptide mass fingerprints.', 'Over 1200 polypeptides were reproducibly detected in 2-DE with a pH range of 3-10. Acetylcholine, oxotremorine, pilocarpine and nicotine treatment caused 16, 9, 8 and 9 protein spots, respectively, expressed differentially. Four protein spots were identified as destrin, FK506 binding protein 1A (FKBP1A), macrophage migration inhibitory factor (MIF) and profilin-1. Western blotting analyses showed that treatment of the cells with cholinergic agonists significantly decreased the expression of destrin, FKBP1A and MIF, and increased the expression of profilin-1.",
            "output": [
                "Does proteomics reveal potential non-neuronal cholinergic receptor-effectors in endothelial cells?"
            ]
        },
        {
            "id": "task847-073b000b42124d0e8eea8f5308436e39",
            "input": "Among many neglected tropical diseases endemic in Honduras, soil-transmitted helminth (STH) infections are of particular importance. However, knowledge gaps remain in terms of risk factors involved in infection transmission. The aim of this study was to investigate risk factors associated with STH infections in schoolchildren living in rural Honduras.', 'A cross-sectional study was conducted among Honduran rural schoolchildren in 2011. Demographic, socio-economic, and epidemiological data were obtained through a standardized questionnaire and STH infections were determined by the Kato-Katz method. Logistic regression models accounting for school clustering were used to assess putative risk factors for infection.', 'A total of 320 children completed the study. Prevalences for any STH and for Ascaris lumbricoides, Trichuris trichiura and hookworms were: 72.5%, 30.3%, 66.9% and 15.9%, respectively. A number of risk factors were identified at the individual, household, and school level. Boys were at increased odds of infection with hookworms (OR 2.33, 95% CI\\u2009=\\u20091.23-4.42). Higher socio-economic status in the family had a protective effect against infections by A. lumbricoides (OR 0.80, 95% CI\\u2009=\\u20090.65-0.99) and T. trichiura (OR 0.77, 95% CI\\u2009=\\u20090.63-0.94).Low school hygiene conditions significantly increased the odds for ascariasis (OR 14.85, 95% CI\\u2009=\\u20097.29-30.24), trichuriasis (OR 7.32, 95% CI\\u2009=\\u20093.71-14.45), mixed infections (OR 9.02, 95% CI\\u2009=\\u20094.66-17.46), and ascariasis intensity of infection (OR 3.32, 95% CI\\u2009=\\u20091.05 -10.52).Children attending schools not providing deworming treatment or that had provided it only once a year were at increased odds of ascariasis (OR 10.40, 95% CI\\u2009=\\u20094.39-24.65), hookworm (OR 2.92, 95% CI\\u2009=\\u20091.09-7.85) and mixed infections (OR 10.57, 95% CI\\u2009=\\u20094.53-24.66).",
            "output": [
                "Are school hygiene and deworming key protective factors for reduced transmission of soil-transmitted helminths among schoolchildren in Honduras?"
            ]
        },
        {
            "id": "task847-9238569ce6214028b8a7af91273657bc",
            "input": "Stress acclimation is an effective mechanism that plants acquired for adaption to dynamic environment. Even though generally considered to be sensitive to low temperature, Cassava, a major tropical crop, can be tolerant to much lower temperature after chilling acclimation. Improvement to chilling resistance could be beneficial to breeding. However, the underlying mechanism and the effects of chilling acclimation on chilling tolerance remain largely unexplored.', 'In order to understand the mechanism of chilling acclimation, we profiled and analyzed the transcriptome and microRNAome of Cassava, using high-throughput deep sequencing, across the normal condition, a moderate chilling stress (14\u00b0C), a harsh stress (4\u00b0C) after chilling acclimation (14\u00b0C), and a chilling shock from 24\u00b0C to 4\u00b0C. The results revealed that moderate stress and chilling shock triggered comparable degrees of transcriptional perturbation, and more importantly, about two thirds of differentially expressed genes reversed their expression from up-regulation to down-regulation or vice versa in response to hash stress after experiencing moderate stress. In addition, microRNAs played important roles in the process of this massive genetic circuitry rewiring. Furthermore, function analysis revealed that chilling acclimation helped the plant develop immunity to further harsh stress by exclusively inducing genes with function for nutrient reservation therefore providing protection, whereas chilling shock induced genes with function for viral reproduction therefore causing damage.",
            "output": [
                "Does chilling acclimation provide immunity to stress by altering regulatory networks and inducing genes with protective functions in cassava?"
            ]
        },
        {
            "id": "task847-dd95f29639ad475cb6c6faea06b8c6a1",
            "input": "Long-QT syndrome (LQTS), a cardiac arrhythmia disorder with variable phenotype, often results in devastating outcomes, including sudden cardiac death. Variable expression, independently from the primary disease-causing mutation, can partly be explained by genetic modifiers. This study investigates variants in a known LQTS-causative gene, AKAP9, for potential LQTS-type 1-modifying effects.', \"Members of a South African LQTS-type 1 founder population (181 noncarriers and 168 mutation carriers) carrying the identical-by-descent KCNQ1 p.Ala341Val (A341V) mutation were evaluated for modifying effects of AKAP9 variants on heart rate-corrected QT interval (QTc), cardiac events, and disease severity. Tag single nucleotide polymorphisms in AKAP9 rs11772585, rs7808587, rs2282972, and rs2961024 (order, 5'-3'positive strand) were genotyped. Associations between phenotypic traits and alleles, genotypes, and haplotypes were statistically assessed, adjusting for the degree of relatedness and confounding variables. The rs2961024 GG genotype, always represented by CGCG haplotype homozygotes, revealed an age-dependent heart rate-corrected QT interval increase (1% per additional 10 years) irrespective of A341V mutation status (P=0.006). The rs11772585 T allele, found uniquely in the TACT haplotype, more than doubled (218%) the risk of cardiac events (P=0.002) in the presence of A341V; additionally, it increased disease severity (P=0.025). The rs7808587 GG genotype was associated with a 74% increase in cardiac event risk (P=0.046), whereas the rs2282972 T allele, predominantly represented by the CATT haplotype, decreased risk by 53% (P=0.001).",
            "output": [
                "Is aKAP9 a genetic modifier of congenital long-QT syndrome type 1?"
            ]
        },
        {
            "id": "task847-a09c046d01fc44d0902d857446cfe945",
            "input": "Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease-induced oxidative stress during oral infection.', 'Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bis-enoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham-infected rats.', 'Rats infected with the periodontal pathogens displayed a five-fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone-targeted antiresorptives bis-enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis-enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive.",
            "output": [
                "Does periodontitis in rats induce systemic oxidative stress that is controlled by bone-targeted antiresorptives?"
            ]
        },
        {
            "id": "task847-ff6640efc04541e38210c71749d80fdf",
            "input": "The sagittal fibular axis serves as an intra-operative landmark during conventional total knee arthroplasty (TKA); however, only a few relevant anatomical studies have been published regarding its use as an extramedullary guide. Furthermore, the correlation between the coronal fibular and tibial mechanical axes in osteoarthritic knees has been only reported once. Here, the hypothesis of this study is that the fibula can be a reliable intra-operative landmark, in the sagittal and coronal planes, among patients with osteoarthritis who have undergone TKA.', 'Osteoarthritic knees (n = 62) after TKA were evaluated using three-dimensional image-matching software. The angles between the tibial mechanical axis and the fibular shaft axis were measured in the sagittal and coronal planes. Moreover, correlations between the angles and patient-specific factors were evaluated.', 'The mean angle between the tibial mechanical and fibular shaft axes was 2.6\u00b0 \u00b1 2.3\u00b0 for posterior inclination in the sagittal plane and 0.9\u00b0 \u00b1 2.0\u00b0 for varus inclination in the coronal plane. The percentage of subjects with the fibular shaft axis within 2\u00b0 of the tibial mechanical axis was 17.7 and 69.3 % in the sagittal and coronal planes, respectively. No patient-specific factors were correlated with the angle between the tibial mechanical and fibular shaft axes.",
            "output": [
                "Are fibular axes a reliable landmark for tibial mechanical axes of osteoarthritic knees that underwent total knee arthroplasty?"
            ]
        },
        {
            "id": "task847-ec1cd324badb4c48b401218a9b2a0de9",
            "input": "Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months. This catastrophic survival rate is the consequence of systematic relapses that could arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. We previously demonstrated that GSCs are able to escape the tumor mass and specifically colonize the adult subventricular zones (SVZs) after transplantation. This specific localization, away from the initial injection site, therefore represents a high-quality model of a clinical obstacle to therapy and relapses because GSCs notably retain the ability to form secondary tumors.', 'In this work, we questioned the role of the CXCL12/CXCR4 signaling in the GSC-specific invasion of the SVZs.', 'We demonstrated that both receptor and ligand are respectively expressed by different GBM cell populations and by the SVZ itself. In vitro migration bio-assays highlighted that human U87MG GSCs isolated from the SVZs (U87MG-SVZ) display stronger migratory abilities in response to recombinant CXCL12 and/or SVZ-conditioned medium (SVZ-CM) compared with cancer cells isolated from the tumor mass (U87MG-TM). Moreover, in vitro inhibition of the CXCR4 signaling significantly decreased the U87MG-SVZ cell migration in response to the SVZ-CM. Very interestingly, treating U87MG-xenografted mice with daily doses of AMD3100, a specific CXCR4 antagonist, prevented the specific invasion of the SVZ. Another in vivo experiment, using CXCR4-invalidated GBM cells, displayed similar results.",
            "output": [
                "Do adult mouse subventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling?"
            ]
        },
        {
            "id": "task847-1f3fffadc408414182fb1803f6cbb83f",
            "input": "The effects of exercise training on nocturnal blood pressure (BP) dipping status remain unclear. African Americans have the highest prevalence of nondippers compared with other racial/ethnic populations. In this 6-month study we tested the hypothesis that long-term aerobic exercise training would increase the levels of nocturnal BP dipping in African American nondippers.', 'We recruited African Americans who were nondiabetic, nonsmoking, and free from cardiovascular and renal disease. For this analysis, only African Americans with a nondipping profile, defined as those with the absence of a nocturnal decline in systolic or diastolic BP (<10% of daytime values), which was determined by ambulatory BP monitoring, were chosen. A pre-post design was used, with baseline and final evaluation including office blood pressure measurement, 24-h ambulatory blood pressure monitoring, fasted blood sampling, and graded exercise testing. Participants engaged in 6 months of supervised aerobic exercise training (AEXT). Following the AEXT intervention, there were significant increases in systolic BP dipping (baseline: 5.8\u00b13.9% vs. final: 9.4\u00b16.1%, P=0.0055) and pulse pressure dipping (baseline: -3.1\u00b16.6% vs. final: 5.0\u00b112.8%, P=0.0109). Of the 18 participants with a nondipping profile at baseline, eight were nonclassified as nondippers after the AEXT intervention. There were no significant changes in office systolic BP/diastolic BP values following the AEXT intervention.",
            "output": [
                "Does chronic aerobic exercise improve blood pressure dipping status in African American nondippers?"
            ]
        },
        {
            "id": "task847-59c5bde0aa2d444b87809c5110302d86",
            "input": "Transcatheter aortic valve implantation (TAVI) without predilatation has fewer procedural steps and thereby potentially fewer complications. This has been demonstrated for the antegrade transapical access; however, whether TAVI can be safely performed without predilatation using the retrograde transfemoral route is unknown.', 'We postulated that TAVI is feasible with a balloon-expandable device without predilatation using the retrograde transfemoral route.', 'Twenty-six consecutive patients with stenosis of the native aortic valve (AV) undergoing transfemoral TAVI with the Edwards SAPIEN XT prosthesis without predilatation were enrolled in this retrospective study and compared with 30 patients treated previously with predilatation.', 'The procedure was successfully performed in all 26 patients, irrespective of the AV area and the extent of AV calcification. At baseline mean AV area, mean AV gradient, and median left ventricular ejection fraction were 0.7 \u00b1 0.2 cm(2) , 36.0 \u00b1 17.3 mm Hg, and 55.0% (interquartile range [IQR], 35.0-60.0], respectively; prior to discharge these values were 1.7 \u00b1 0.3 (P < 0.001), 9.8 \u00b1 6.1 mm Hg (P < 0.001), and 57.5% (IQR, 38.7-60.0) (P = not significant). Postdilatation was required in 3 patients due to aortic regurgitation > 2\u00b0; this was reduced by the procedure to < 2\u00b0 in all cases. Radiation dose and amount of contrast dye were significantly reduced in comparison with the predilatation group. No periprocedural neurological adverse events occurred. Mortality at 30 days was 0%.",
            "output": [
                "Is transfemoral aortic valve implantation of Edwards SAPIEN XT without predilatation feasible?"
            ]
        },
        {
            "id": "task847-7f4368d655d74928bebaf19d73e7d2ed",
            "input": "Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients.', 'This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment.', 'Viral loads of E7 oncogenes for HPV 16/18 were measured by quantitative PCR tests in paraffin-embedded lesional specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable Cox regression analysis was used to identify the independent prognostic factors for 5-year DM and C statistics were further computed.', 'By multivariable analysis, high HPV 16 E7 viral load (\u226515.0 copies/genome); high HPV 18 E7 viral load (\u226515.0 copies/genome); pathological N2 status (pN2); tumor depth \u226511 mm; extracapsular spread (ECS); and level IV/V metastases were independent risk factors for DM. We further identified three prognostic groups. In the high-risk group (level IV/V metastases or high HPV 16/18 E7 viral load plus pN2, tumor depth \u226511 mm, or ECS), the 5-year distant metastasis rate was 74%. In the intermediate-risk group (high HPV 16/18 E7 viral load, pN2, tumor depth \u226511 mm, or ECS), the 5-year DM rate was 17%. Finally, the 5-year DM rate was 1% in the low-risk group (no risk factors). The value of the C statistics was 0.78.",
            "output": [
                "Do human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-6e15ee04cf86469eac65e23ea6f811aa",
            "input": "The objective of this study was to use a well-established monkey model of atherosclerosis to determine how life stage and preexisting atherosclerosis influence the effectiveness of high-isoflavone soy diet in inhibiting progression of atherosclerosis.', 'For 34 months, premenopausal monkeys were fed an atherogenic diet, with protein derived primarily from either animal sources (casein-lactalbumin [CL], n = 37) or high-isoflavone soy beans (Soy, n = 34). Animals were ovariectomized and randomized to groups fed the same diet (CL-CL, n = 20; Soy-Soy, n = 17) or an alternate diet (CL-Soy, n = 17; Soy-CL, n = 17) for an additional 34 months. At ovariectomy, the left common iliac artery was removed to determine the amount of premenopausal atherosclerosis. At necropsy, the right common iliac artery and coronary arteries were collected, and atherosclerosis extent was quantified. CL-CL condition was considered \"control.\"', 'Modeling Asian women who remain in Asia, monkeys fed soy protein both premenopausally and postmenopausally had a markedly reduced extent of coronary artery atherosclerosis relative to CL controls (P = 0.008). The subset of animals that modeled Asian women who migrate to a Western country (consuming soy premenopausally and CL postmenopausally) had increased progression of postmenopausal iliac artery atherosclerosis (P = 0.003) and was not protected against the development of coronary artery atherosclerosis relative to controls. Relevant to the administration of soy diets to postmenopausal Western women, monkeys fed CL premenopausally and switched to soy postmenopausally derived atheroprotective benefits only if they began the postmenopausal treatment period with relatively small (below the median) plaques. Relative to controls, this group (with small plaques at ovariectomy) had reduced progression of iliac atherosclerosis (P = 0.038) and smaller coronary artery plaques (P = 0.0001) that were less complicated (P = 0.05) relative to controls.",
            "output": [
                "Are beneficial effects of soy supplementation on postmenopausal atherosclerosis dependent on pretreatment stage of plaque progression?"
            ]
        },
        {
            "id": "task847-76b8918e7d0844b19c02b85573fa2b01",
            "input": "This study aims to evaluate the potential effects of renal function variations on vascular structure before the development of hypertension.', 'This pilot study included 141 postmenopausal women without evidence of renal dysfunction or hypertension. Markers of renal function and levels of glomerular filtration rate (GFR)--using standard calculations (GFR based on levels of creatinine [GFR(epi)]) and newer creatinine and/or cystatin calculations (GFR based on levels of creatinine and cystatin [GFR(cr cystatin)] and GFR based on levels of cystatin [GFR(cystatin)])--were associated with hemodynamic parameters and markers of vascular structure (intima-media thickness [IMT] and presence of atheromatous plaques in carotid and femoral arteries).', 'Levels of GFR(epi), GFR(cr cystatin), and GFR(cystatin) exhibited a significant negative correlation with femoral artery IMT, whereas levels of GFR(epi) correlated significantly with mean carotid bulb (CB) IMT. Multivariate analysis showed that CB-IMT was predicted by GFR(epi) levels and age (\u03b2-coefficient = -0.212, P = 0.020), whereas femoral artery IMT was predicted by GFR(epi) levels (\u03b2-coefficient = -0.293, P = 0.001). GFR(epi) levels lower than the 25th percentile were associated with higher CB-IMT (P = 0.009), femoral artery IMT (P = 0.001), and combined IMT (P = 0.035) compared with higher GFR(epi) levels. Moreover, GFR(epi) levels greater than the 25th percentile were associated with lower odds for the presence of atherosclerotic plaques at the CB and carotid arteries combined (CB: odds ratio, 0.146; P = 0.006; combined: odds ratio, 0.249; P = 0.043) compared with lower GFR(epi) levels.",
            "output": [
                "Are variations in glomerular filtration rate associated with subclinical atherosclerosis in healthy postmenopausal women?"
            ]
        },
        {
            "id": "task847-31723c29855245a9ac0d9d6b16024df6",
            "input": "Experimentally measured pullout forces for stent grafts (SGs) are used in clinical discussions and as reference values in bench studies and computer simulations. Previous values of these forces are available from studies in which the SG was pulled out in the straight caudal direction. However, clinical and numerical studies have suggested that displacement forces acting on SGs are directed more anteriorly. The objective of this study was to measure pullout forces as a function of angulation and to test the hypothesis that pullout forces decrease with increasing angulation.', 'Six different SGs (Bolton Treovance, Cook Zenith Flex, Cook Zenith LP, Medtronic Endurant, Medtronic Talent, and Vascutek Anaconda) were deployed in fresh bovine aortas, then pulled out by an electronic motor at 1 mm/s, while tension force was measured continuously with a digital load cell. The SG off-axis angulation was changed from 0 to 90 degrees in increments of 10 degrees. The test system was submerged in a custom-built temperature-controlled saline bath at 37\u00b0C. At least three tests were performed for each device at each angle (with the exception of the Cook Zenith Flex, which experienced plastic deformation of its barbs after a single test per device). Each aortic specimen was used only once and then discarded. Hand-sutured graft anastomoses were also tested at 0 degrees to provide a reference value.', 'A total of 374 pullout tests were performed for the SGs and anastomoses. Sixty-four tests were excluded because of failure of the aorta or apparatus before device pullout. The remaining 310 tests showed pullout forces that demonstrated a decrease in the average pullout force for all six devices from 0 to 90 degrees (Bolton Treovance from 39.3 N to 23.9 N; Cook Zenith Flex from 59.8 N to 48.9 N; Cook Zenith LP from 50.3 N to 41.8 N; Medtronic Endurant from 29.9 N to 25.8 N; Medtronic Talent from 6.0 N to 5.5 N; and Vascutek Anaconda from 37.0 N to 30.3 N). For reference, the mean pullout force for the hand-sutured anastomoses was 63 N.",
            "output": [
                "Does increasing angulation decrease measured aortic stent graft pullout forces?"
            ]
        },
        {
            "id": "task847-79b4413945ff42d98c04d8a047af9f53",
            "input": "Salivary gland adenoid cystic carcinoma (ACC) is one of the most common malignant tumours in the oral and maxillofacial region, and has high aggressive potential. Tumour and stroma interactions are critical in determining the biological characteristics of malignancy. The aim of this study was to investigate the presence of myofibroblasts and their roles in the invasive characteristics of ACC.', 'Immunohistochemistry was used to detect the expression of vimentin (VIM), \u03b1-smooth muscle actin (\u03b1-SMA), matrix metalloproteinase 2 (MMP2) and CD34 in ACCs and normal salivary gland controls. A significant difference in \u03b1-SMA expression was found between normal controls and ACCs, suggesting the presence of myofibroblasts in ACCs. Immunohistochemical staining also demonstrated higher MMP2 expression in the stroma of ACCs than in the controls (P < 0.001). Primary culture of myofibroblasts from one ACC showed great invasive activity, with high expression of MMP2 and C-X-C motif chemokine 12 (CXCL12) by reverse transcription polymerase chain reaction (RT-PCR) analysis.",
            "output": [
                "Do myofibroblasts from salivary gland adenoid cystic carcinomas promote cancer invasion by expressing MMP2 and CXCL12?"
            ]
        },
        {
            "id": "task847-43c77169c82b4a0d912c270b5fb1b172",
            "input": "Obesity is associated with metabolic derangement and non-alcoholic fatty liver disease (NAFLD). Macrophages are involved in liver inflammation and fibrosis, and soluble (s)CD163 is a macrophage activation marker.', 'To associate sCD163 with parameters of paediatric obesity and NAFLD, as well as changes in these parameters during lifestyle intervention.', 'We studied 117 obese children during a 10-week lifestyle intervention; 71 completed the 12-month follow-up. We recorded clinical and biochemical data, and performed liver ultrasonography.', 'Baseline sCD163 was higher in children with elevated alanine transaminase (ALT) (2.3\\u2009\u00b1\\u20090.7 vs. 2.0\\u2009\u00b1\\u20090.6\\u2009mg\\u2009L(-1), P\\u2009=\\u20090.03), steatosis (2.3\\u2009\u00b1\\u20090.7 vs. 2.0\\u2009\u00b1\\u20090.6\\u2009mg\\u2009L(-1), P\\u2009=\\u20090.01) and high paediatric NAFLD fibrosis index (2.3\\u2009\u00b1\\u20090.7 vs. 1.9\\u2009\u00b1\\u20090.6\\u2009mg\\u2009L(-1) , P\\u2009=\\u20090.03). Baseline sCD163 was independently associated with ALT, cholesterol and high-sensitivity C-reactive protein (hs-CRP). The change in sCD163 during lifestyle intervention was associated with changes in ALT, homeostatic model assessment of insulin resistance (HOMA-IR), hs-CRP and cholesterol, and inversely associated with the change in high-density lipoprotein cholesterol.",
            "output": [
                "Is the macrophage activation marker sCD163 associated with changes in NAFLD and metabolic profile during lifestyle intervention in obese children?"
            ]
        },
        {
            "id": "task847-9fd0e83a27f04f22a9540e0d51a0ba56",
            "input": "Women with antiphospholipid syndrome (APS) are at increased risk of recurrent pregnancy loss (RPL) and preeclampsia. Antiphospholipid antibodies (aPL) directly alter trophoblast function. Treatment with low molecular weight heparin (LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sFlt-1 release, an anti-angiogenic factor associated with preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia, this study sought to determine the effect of vitamin D on trophoblast function in the setting of aPL and LMWH.', 'A human first trimester trophoblast cell line (HTR8) and primary trophoblast cultures were treated with or without aPL in the presence and absence of vitamin D, LMWH or both. Trophoblast secretion of inflammatory cytokines and angiogenic factors were measured by ELISA.', 'Vitamin D alone or in combination with LMWH attenuated the aPL-induced trophoblast inflammatory response in the HTR8 cells and primary cultures. While vitamin D did not have any impact on aPL-mediated modulation of angiogenic factors in the primary trophoblast, it significantly inhibited LMWH-induced sFlt-1 release.",
            "output": [
                "Does vitamin D reverse aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast?"
            ]
        },
        {
            "id": "task847-4e442562de824fa8af979400f1127a1f",
            "input": "Wnt signaling is a master regulator of joint homeostasis, but its role in osteoarthritis (OA) remains unclear. This study was undertaken to characterize the activation of Wnt/\u03b2-catenin in knee joints of mice with OA and to assess how inhibiting this pathway in bone could affect cartilage.', 'OA was induced by partial meniscectomy in Topgal mice and in transgenic mice overexpressing Dkk-1 under the control of the 2.3-kb Col1a1 promoter (Col1a1-Dkk-1-Tg mice). Wnt/\u03b2-catenin activation was assessed by X-Gal staining at baseline and at weeks 4, 6, and 9. Cartilage and bone damage was analyzed in Col1a1-Dkk-1-Tg mice with OA at week 6. Primary chondrocytes and cartilage explants were used to assess the effect of Dkk-1 on cartilage catabolism.', 'In meniscectomized Topgal mice, Wnt was mainly activated in osteocytes from the subchondral bone at week 6 after OA induction, as well as in osteophytes and synovium at week 4. Chondrocytes from damaged zones expressed X-Gal from week 4. Dkk-1 expression was high in chondrocytes in control mouse knees (mean \u00b1 SEM 84.2 \u00b1 3.1%) but decreased greatly in knees of meniscectomized mice from week 4 (mean \u00b1 SEM 14.4 \u00b1 3.8%). The OA score was lower in meniscectomized Col1a1-Dkk-1-Tg mice at week 6 compared with wild-type mice (5.1 \u00b1 0.6 versus 8.4 \u00b1 0.6; P = 0.002). Subchondral bone fraction and osteophyte volume were decreased. However, cartilage explants from Col1a1-Dkk-1-Tg mice showed proteoglycan loss and increased NITEGE expression. Expression of vascular endothelial growth factor (VEGF) was reduced in osteoblasts from Col1a1-Dkk-1-Tg mice, thereby decreasing expression of messenger RNA for matrix metalloproteinases in chondrocytes.",
            "output": [
                "Does dkk-1-mediated inhibition of Wnt signaling in bone ameliorate osteoarthritis in mice?"
            ]
        },
        {
            "id": "task847-20582256f3b742a4818be7d2dab94d14",
            "input": "Fluid balance for the surgical patient has been proven very important for the postoperative outcome and development of complications. The aim of this study was to evaluate, for the first time in modern times, the accordance between nurse-based fluid charting (cumulated fluid balance) and body weight change for general surgical patients.', 'This was a descriptive study with prospectively collected data from two clinical randomized multicenter trials. A total of 113 patients from American Society of Anesthesiology group I-III undergoing elective colorectal surgery were included. Cumulated fluid balance and body weight change were charted preoperatively and daily at the same time during a postoperative period of 6 days. Differences were calculated by subtracting cumulated fluid balance from body weight change (1 g = 1 mL), and agreement was assessed by making Bland-Altman plots as well as Pearson correlations.', 'From day 1 to 4, the mean difference between cumulated fluid balance and body weight change was below 0.4 kg/L. On day 5 and 6, the discrepancies increased with mean differences of, respectively, 1.2 kg/L (p < 0.002*) and 2 kg/L (p < 0.0001*). Bland-Altman plots showed increasingly poor agreement for all postoperative days with wide limits of agreement, ranging from more than 6 kg/L to almost 10 kg/L. Pearson correlations were moderate to strong at all times ranging from 0.437 (day 1) to 0.758 (day 4).",
            "output": [
                "Is clinical Assessment of Fluid Balance Incomplete for Colorectal Surgical Patients?"
            ]
        },
        {
            "id": "task847-61137352e6264cb6b4f0f1cc45748f56",
            "input": "Back pain is among the most prevalent pain disorders causing chronic disability among adults, and insomnia is a common co-morbidity. However, whether insomnia precedes back pain or vice versa remains unclear. The current study tested the temporal association between insomnia and back pain.', 'A longitudinal design was used to investigate whether changes in insomnia over time predict the onset of back pain and vice versa. The study was conducted on a cohort of active healthy working adults (N = 2,131, 34% women) at three time points (T1, T2, and T3) over a period of 3.7 years (range = 2.2-5.12) years. Logistic regression analysis was used to test whether increased insomnia symptoms from T1 to T2 predicted the onset of new back pain. Ordinary least squares regression was used to test whether the existence of back pain at T2 predicted an increase in insomnia from T2 to T3.', 'The results indicated that after controlling for socioeconomic variables, self-reported health, lifestyle behaviors, and anthropometrics, a T1-T2 increase in insomnia symptoms was associated with a 1.40-fold increased risk of back pain at T3 (OR = 1.40; 95% CI = 1.10-1.71). No support was found for reverse causation; i.e., that back pain predicts subsequent increase in insomnia.",
            "output": [
                "Do increased insomnia symptoms predict the onset of back pain among employed adults?"
            ]
        },
        {
            "id": "task847-fc84c2af30fd413fa46f618b4ab9a9b7",
            "input": "To test the use of diffusion-weighted magnetic resonance imaging (DW-MRI) to differentiate between different degrees of severity of acute pancreatitis (AP).', 'Thirty-six patients who underwent DW-MRI and magnetic resonance cholangiopancreatography were divided into patients with mild AP (mAP, n = 15), patients with necrotizing AP (nAP, n = 8), and patients with a normal pancreas (nP, n = 15; controls). The pancreas was divided into head, body, and tail, and each segment was classified according to image features: pattern 1, normal; pattern 2, mild inflammation; and pattern 3, necrosis. Apparent diffusion coefficients (ADCs) were measured in each segment and correlated with clinical diagnoses.', 'A total of 108 segments was assessed (three segments per patient). Segments classified as pattern 1 in the nP and mAP groups showed similar ADC values (P = 0.29). ADC values calculated for the pancreatic segments grouped according to the different image patterns (1-3) were significantly different (P < 0.001). Comparisons revealed significant differences in signal intensity between all three patterns (P < 0.05).",
            "output": [
                "Does diffusion-weighted magnetic resonance imaging indicate the severity of acute pancreatitis?"
            ]
        },
        {
            "id": "task847-3a2efdab2b5143b48396d4c75c57c5c9",
            "input": "This study characterizes ovariectomized (OVX)-induced osteoporotic fracture healing with focus on estrogen receptors (ERs). Callus formation plays a critical role in fracture healing, and ERs are well-known mechanosensors in osteogenic pathways. It was hypothesized that callus formation was related to and partially determined by the difference in expression patterns of ERs in both normal and OVX-induced osteoporotic fractures.', 'Closed femoral fracture in SHAM and ovariectomized rats were used in this study. Weekly callus width (CW) and area (CA), endpoint mechanical properties, gene expressions of Col-1, BMP-2, ER-\u03b1, ER-\u03b2 and ER-\u03b1:ER-\u03b2 ratios (ER-ratios), and correlations were assessed at 2, 4 and 8 weeks post-fracture.', 'CW and CA results confirmed that OVX-induced osteoporotic fracture was delayed at 2-4 weeks with impaired endpoint mechanical properties. Gene expressions of ER-\u03b1 and ER-\u03b2 were higher in the SHAM group at week 2 (p < 0.05) and later lowered at week 8; whereas the OVX group showed an opposing trend. Moderate correlation existed between ER-\u03b1 and BMP-2 (0.545, p = 0.003), and ER-ratio and BMP-2 (0.601, p = 0.001), and BMP-2 to CW and CA (r = 0.709, p = 0.000 and r = 0.588, p = 0.001, respectively). ER-\u03b1 and ER-\u03b2 proteins expressions were confirmed by immunohistochemistry at the fracture callus in reparative progenitor cells, osteoblasts- and osteoclasts-like cells.",
            "output": [
                "Is callus formation related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing?"
            ]
        },
        {
            "id": "task847-27fa1fb1578c43f48921c5a63a875b59",
            "input": "The purpose of this study was to examine whether oral administration of an angiotensin II type 1 receptor blocker (ARB) inhibited in-stent neointimal hyperplasia in carotid arteries of hypercholesterolemic rabbits.', 'Eleven male New Zealand white rabbits were subjected to endothelial injuries of the right common carotid arteries using a balloon catheter and then received chow containing 1% cholesterol for 6 weeks. A balloon-expandable stainless steel stent was subsequently inserted at the injured sites of the arteries. After stenting, five rabbits were randomly treated with an oral ARB, candesartan cilexetil (5 mg/kg per day orally), while the remaining six rabbits acted as untreated controls. Four weeks after the implantation, the rabbits were killed, followed by collection of the arteries including the stents. After careful removal of the stents, tissue sections were prepared and analyzed by morphometric and immunohistochemical methods.', 'The mean thickness of the neointima was 53.6 \u00b1 17.0 \u03bcm in the ARB-treated group, which was significantly reduced compared to 95.9 \u00b1 16.7 \u03bcm in the control group (P = 0.0012). Immunohistochemistry showed a decrease in accumulation of macrophages and tenascin-C expression in the arterial wall in the ARB-treated animals.",
            "output": [
                "Do angiotensin II type 1 receptor blockers suppress neointimal hyperplasia after stent implantation in carotid arteries of hypercholesterolemic rabbits?"
            ]
        },
        {
            "id": "task847-fe985186e3c048bfadbce5a322128d63",
            "input": "Prostate cancer is a common malignancy in men, and inevitably some patients experience biochemical recurrence after radical prostatectomy. To date, there are no reliable predictors for prostate cancer recurrence, and novel predictors are urgently needed. PCDH10 (protocadherin-10) is a novel tumor suppressor gene, which is down-regulated by promoter methylation in prostate cancer. The aim of this study was to evaluate the feasibility of using PCDH10 methylation to predict the biochemical recurrence (BCR) of prostate cancer after radical prostatectomy.', 'Fresh tissue samples were obtained from 151 patients with primary prostate cancer, and from 34 patients with benign prostatic hyperplasia (BPH) as control. The methylation status of PCDH10 in prostate cancer tissues and controls were examined using methylation-specific PCR (MSP), and then associated with clinicopathological features and BCR-free survival of patients with prostate cancer.', 'We found that PCDH10 methylation was detected in 79 (52.3%) patients with prostate cancer, but no methylation was found in controls (P<0.0001). Moreover, PCDH10 methylation was significantly associated with higher preoperative prostate-specific antigen (PSA) level (P <0.0001), higher Gleason Score (P<0.0001), advanced clinical stage (P=0.0002), lymph node metastasis (P=0.0389), angiolymphatic invasion (P=0.0303), and biochemical recurrence (P=0.0068). Moreover, PCDH10 methylation was associated with poor BCR-free survival (P<0.0001), and may be used as an independent predictor of BCR-free survival (P=0.0046).",
            "output": [
                "Does aberrant methylation of PCDH10 predict worse biochemical recurrence-free survival in patients with prostate cancer after radical prostatectomy?"
            ]
        },
        {
            "id": "task847-0447787ea58746e59d5caa5e8245c551",
            "input": "Our previous reports demonstrated that genetic deletion of \u03bc-opioid receptor has no influence on the anaesthetic and antinociceptive effects of nitrous oxide (N2O) in mice, and that an antagonist selective for \u03ba-opioid receptor (KOP), but not that selective for \u03b4-opioid receptor, suppresses the antinociceptive effect of N2O. However, it is not known whether genetic deletion of KOP affects the N2O actions.', 'We measured the minimum alveolar concentration (MAC) of volatile anaesthetics in the absence and presence of N2O. The antinociceptive action of N2O was tested by an acetic acid-writhing test and a hot-plate test. The number of c-Fos-immunopositive cells in sections from the lumbar spinal cord was counted to test whether the descending inhibitory system participates in the pharmacological action of N2O. The hypnotic action of N2O was assessed by measuring the N2O-induced decrease in the EC50 for loss of the righting reflex (EC50-LORR) of sevoflurane.', 'Sevoflurane MAC was not significantly reduced by N2O and its antinociceptive action was almost completely abolished in KOP-knockout (KO) mice. The N2O-induced increase in c-Fos-immunopositive cells in laminae III-IV of the lumbar spinal cord was significant in wild-type (WT), but not in KOP-KO mice. In contrast, sevoflurane EC50-LORR was similarly reduced by N2O in WT and KOP-KO mice.",
            "output": [
                "Does \u03ba-Opioid receptor mediate the antinociceptive effect of nitrous oxide in mice?"
            ]
        },
        {
            "id": "task847-64a06e05fc6c48e39d3518f5db319f93",
            "input": "Ovarian cancer (OvCa) is the most lethal gynecologic malignancy in the United States because of chemoresistant recurrent disease. Our objective was to investigate the efficacy of inhibiting the Notch pathway with a \u03b3-secretase inhibitor (GSI) in an OvCa patient-derived xenograft model as a single agent therapy and in combination with standard chemotherapy.', 'Immunocompromised mice bearing xenografts derived from clinically platinum-sensitive human ovarian serous carcinomas were treated with vehicle, GSI (MRK-003) alone, paclitaxel and carboplatin (P/C) alone, or the combination of GSI and P/C. Mice bearing platinum-resistant xenografts were given GSI with or without paclitaxel. Gene transcript levels of the Notch pathway target Hes1 were analyzed using RT-PCR. Notch1 and Notch3 protein levels were evaluated. The Wilcoxon rank-sum test was used to assess significance between the different treatment groups.', 'Expression of Notch1 and 3 was variable. GSI alone decreased tumor growth in two of three platinum-sensitive ovarian tumors (p\\u2009<\\u20090.05), as well as in one of three platinum-sensitive tumors (p\\u2009=\\u20090.04). The combination of GSI and paclitaxel was significantly more effective than GSI alone and paclitaxel alone in all platinum-resistant ovarian tumors (all p\\u2009<\\u20090.05). The addition of GSI did not alter the effect of P/C in platinum-sensitive tumors. Interestingly, although the response of each tumor to chronic GSI exposure did not correlate with its endogenous level of Notch expression, GSI did negatively affect Notch signaling in an acute setting.",
            "output": [
                "Does inhibition of notch signaling in combination with Paclitaxel reduce platinum-resistant ovarian tumor growth?"
            ]
        },
        {
            "id": "task847-df967722034b4928aefe167694c6a9e6",
            "input": "Stem/progenitor cells are in the focus of research as a future therapeutic option to stimulate regeneration in diseased renal parenchyma. However, current data indicate that successful seeding of implanted stem/progenitor cells is prevented by harmful interstitial fluid and altered extracellular matrix. To find out possible parameters for cell adaptation, the present investigation was performed.', 'Renal stem/progenitor cells were mounted in an artificial interstitium for perfusion culture. Exposure to chemically defined but CO2-independent culture media was tested during 13\\xa0days. Cell biological features were then analyzed by histochemistry, while structural details were investigated by transmission electron microscopy after conventional and improved fixation of specimens.', \"Culture of renal stem/progenitor cells as well in Leibovitz's L-15 Medium as CO2 Independent Medium shows in fluorescence microscopy spatial development of numerous tubules. Specimens of both media fixed by conventional glutaraldehyde exhibit in electron microscopy a homogeneous cell population in developed tubules. In contrast, fixation by glutaraldehyde including tannic acid illuminates that dispersed dark marked cells of unknown function are present. The screening further demonstrates that the dark cell type does not comply with cells found in embryonic, maturing or matured renal parenchyma.",
            "output": [
                "Does tannic acid label indicate abnormal cell development coinciding with regeneration of renal tubules?"
            ]
        },
        {
            "id": "task847-9b94ca590db3463c9cf86292c3fbc509",
            "input": "Endoplasmic reticulum (ER) stress is induced in many forms of chronic liver disease and may promote the development of hepatocellular carcinoma. The activator protein 1 (AP-1) complex is a transcription factor that promotes hepatic carcinogenesis in response to cellular stress. The aim of this study was to determine the role of ER stress in the regulation of the hepatic AP-1 complex.', 'Human hepatocellular carcinoma (HepG2) cells and C57BL/6J mice were subjected to pharmacologic ER stress and the expression of AP-1-associated genes and proteins was assessed. To determine the role of MAPK signaling in ER stress-induced AP-1 activation, ER stress was induced in JNK- and ERK-inhibited HepG2 cells.', 'Induction of ER stress promoted the activation of both Jun- and Fos-related genes and proteins of the AP-1 complex in HepG2 cells and murine liver. Inhibition of ERK phosphorylation in HepG2 cells completely prevented ER stress-induced activation of the fos-related components of AP-1 whereas activation of Jun-related components was only partially attenuated. Conversely, inhibition of JNK phosphorylation in HepG2 cells reduced ER stress-induced activation of Jun-related components but did not prevent activation of fos-related components.",
            "output": [
                "Does endoplasmic reticulum stress activate the hepatic activator protein 1 complex via mitogen activated protein kinase-dependent signaling pathways?"
            ]
        },
        {
            "id": "task847-e254285420e54c2da77e8102b88b8569",
            "input": "Nuclear reprogramming inculcates pluripotent capacity by which de novo tissue differentiation is enabled. Yet, introduction of ectopic reprogramming factors may desynchronize natural developmental schedules. This study aims to evaluate the effect of imposed transgene load on the cardiogenic competency of induced pluripotent stem (iPS) cells.', 'Targeted inclusion and exclusion of reprogramming transgenes (c-MYC, KLF4, OCT4, and SOX2) was achieved using a drug-inducible and removable cassette according to the piggyBac transposon/transposase system. Pulsed transgene overexpression, before iPS cell differentiation, hindered cardiogenic outcomes. Delayed in counterparts with maintained integrated transgenes, transgene removal enabled proficient differentiation of iPS cells into functional cardiac tissue. Transgene-free iPS cells generated reproducible beating activity with robust expression of cardiac \u03b1-actinin, connexin 43, myosin light chain 2a, \u03b1/\u03b2-myosin heavy chain, and troponin I. Although operational excitation-contraction coupling was demonstrable in the presence or absence of transgenes, factor-free derivatives exhibited an expedited maturing phenotype with canonical responsiveness to adrenergic stimulation.",
            "output": [
                "Is iPS cell-derived cardiogenicity hindered by sustained integration of reprogramming transgenes?"
            ]
        },
        {
            "id": "task847-a2ff49e5a4464a13aa1b18a5a0427871",
            "input": "Heme oxygenase catalyzes the conversion of heme to iron, carbon monoxide and biliverdin employing oxygen and reducing equivalents. This enzyme is essential for heme-iron utilization and contributes to virulence in Leptospira interrogans.', 'A phylogenetic analysis was performed using heme oxygenases sequences from different organisms including saprophytic and pathogenic Leptospira species. L. interrogans heme oxygenase (LepHO) was cloned, overexpressed and purified. The structural and enzymatic properties of LepHO were analyzed by UV-vis spectrophotometry and (1)H NMR. Heme-degrading activity, ferrous iron release and biliverdin production were studied with different redox partners.', 'A plastidic type, high efficiently ferredoxin-NADP(+) reductase (LepFNR) provides the electrons for heme turnover by heme oxygenase in L. interrogans. This catalytic reaction does not require a ferredoxin. Moreover, LepFNR drives the heme degradation to completeness producing free iron and \u03b1-biliverdin as the final products. The phylogenetic divergence between heme oxygenases from saprophytic and pathogenic species supports the functional role of this enzyme in L. interrogans pathogenesis.",
            "output": [
                "Does heme-iron utilization by Leptospira interrogans require a heme oxygenase and a plastidic-type ferredoxin-NADP ( + ) reductase?"
            ]
        },
        {
            "id": "task847-b58707394f744582a52c647d76a982f1",
            "input": "Asteatotic eczema (AE) is characterized by itchy, dry, rough, and scaling skin. The treatments for AE are mainly emollients, usually containing urea, lactic acid, or a lactate salt. N-palmitoylethanolamine (PEA) and N-acetylethanolamine (AEA) are both endogenous lipids used as novel therapeutic tools in the treatment of many skin diseases. The purpose of this study was to compare a PEA/AEA emollient with a traditional emollient in the treatment of AE.', \"A monocentric, randomized, double-blind, comparative trial was conducted in 60 AE patients to evaluate and compare the efficacy of the two emollients. The level of skin dryness among the subjects ranged from mild to moderate. The subjects' skin barrier function and the current perception threshold were tested for 28 days by clinical scoring and bioengineering technology.\", 'The results showed that, although some aspects were improved in both groups, the group using the emollient containing PEA/AEA presented a better skin surface change in capacitance. However, the most impressive finding was the ability of the PEA/AEA emollient to increase the 5 Hz current perception threshold to a normal level after 7 days, with a significant difference between values at baseline and after 14 days. A current perception threshold of 5 Hz was positively and significantly correlated with skin surface hydration and negatively correlated with transepidermal water loss in the PEA/AEA emollient group.",
            "output": [
                "Are n-palmitoylethanolamine and N-acetylethanolamine effective in asteatotic eczema : results of a randomized , double-blind , controlled study in 60 patients?"
            ]
        },
        {
            "id": "task847-922841613e784241a7318e7f93fce001",
            "input": "Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune inflammatory demyelination that is mediated by Th1 and Th17 cells. The transcription factor interferon regulatory factor 3 (IRF3) is activated by pathogen recognition receptors and induces interferon-\u03b2 production.', 'To determine the role of IRF3 in autoimmune inflammation, we immunised wild-type (WT) and irf3(-/-) mice to induce EAE. Splenocytes from WT and irf3(-/-) mice were also activated in vitro in Th17-polarising conditions.', 'Clinical signs of disease were significantly lower in mice lacking IRF3, with reduced Th1 and Th17 cells in the central nervous system. Peripheral T-cell responses were also diminished, including impaired proliferation and Th17 development in irf3(-/-) mice. Myelin-reactive CD4+ cells lacking IRF3 completely failed to transfer EAE in Th17-polarised models as did WT cells transferred into irf3(-/-) recipients. Furthermore, IRF3 deficiency in non-CD4+ cells conferred impairment of Th17 development in antigen-activated cultures.",
            "output": [
                "Is interferon regulatory factor ( IRF ) 3 critical for the development of experimental autoimmune encephalomyelitis?"
            ]
        },
        {
            "id": "task847-a6dc103f37a641429a95d8a6c674b6e1",
            "input": "Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathologic and molecular classification of these tumors has been a significant challenge. This study examines the protein expression of a large number of human STS, including subtype heterogeneity, using two-dimensional gel proteomics. In addition, detailed proteome profiles of a subset of pleomorphic STS specimens using an in-depth mass-spectrometry approach identified subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biologic nodes like apoptosis, cytoskeleton remodeling, and telomere regulation are differentially regulated among these subgroups. Finally, investigating the similarities between protein expression of leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar protein expression profiles for these tumors, in comparison with pleomorphic leiomyosarcomas.",
            "output": [
                "Does discovery-based protein expression profiling identify distinct subgroups and pathways in leiomyosarcomas?"
            ]
        },
        {
            "id": "task847-ca287b6fb3f94d939cd74f63e04d07d6",
            "input": "miRNAs have been implicated in the regulation of key metabolic, inflammatory, and malignant pathways; hence, they might be considered both predictors and players of cancer development.', 'Using a case-control study design nested in the ORDET prospective cohort study, we addressed the possibility that specific mRNAs can serve as early predictors of breast cancer incidence in postmenopausal women. We compared leukocyte miRNA profiles of 133 incident postmenopausal breast cancer cases and profiles of 133 women who remained healthy over a follow-up period of 20 years.', 'The analysis identified 20 differentially expressed miRNAs, 15 of which were downregulated. Of the 20 miRNAs, miR145-5p and miR145-3p, each derived from another arm of the respective pre-miRNA, were consistently and significantly downregulated in all the databases that we surveyed. For example, analysis of more than 1,500 patients (the UK Metabric cohort) indicated that high abundance of miR145-3p and miR145-5p was associated with longer, and for miR145-3p also statistically significant, survival. The experimental data attributed different roles to the identified miRNAs: Although the 5p isoform was associated with invasion and metastasis, the other isoform seems related to cell proliferation.",
            "output": [
                "Is downregulation of microRNAs 145-3p and 145-5p a long-term predictor of postmenopausal breast cancer risk : The ORDET prospective study?"
            ]
        },
        {
            "id": "task847-2964cf5772a5421c9657a2eb6a77b258",
            "input": "KIR genes coding for natural killer cell immunoglobulin-like receptors, KIR, influence the effector and regulatory function of NK cells as well as some subpopulations of T lymphocytes (e.g. CD4+CD28-KIR+) depending on presence of ligands (particularly HLA-C molecules). KIR-KIR ligand interaction may lead to the development of autoimmune disorders, including rheumatoid arthritis (RA). However, their role in the response of RA patients to methotrexate therapy is not known.', 'KIR genes and KIR-ligand (HLA-C C1/C2 allomorphs) genotyping was performed using the PCR-SSP method in 312 RA patients (179 classified as good responders and 133 as poor responders using DAS28 criteria). Thus, we evaluated the association of KIR genes and HLA-C allomorphs with the response to methotrexate (MTX) treatment.', 'We observed that patients possessing the full-length KIR2DS4 (KIR2DS4f) gene had a lower chance of responding in comparison to KIR2DS4f-negative cases. This phenomenon was observed both in erosive disease (ED) and rheumatoid factor (RF) positive and in ED- and RF-negative patients. Interestingly, the observed effect of the KIR2DS4f gene was strongest in individuals possessing medium values (20-33 mm/h) of the erythrocyte sedimentation rate (ESR). Patients with high ESR values had low probability and, in contrast, patients with low ESR had a high probability of MTX response, and the presence of KIR2DS4f did not affect their outcome. Additionally, we show that the KIR2DS4f effect did not depend on the presence of either C1 or C2 allomorphs.",
            "output": [
                "Does presence of the full-length KIR2DS4 gene reduce the chance of rheumatoid arthritis patients to respond to methotrexate treatment?"
            ]
        },
        {
            "id": "task847-f9612ccb129643dabf3e2e86265ecdea",
            "input": "Previous studies demonstrated that a history of childhood trauma is linked to mental disorders in adulthood, particularly to depression. Adverse childhood experiences are also considered to contribute to the risk of hypochondriasis, but the results of previous studies have not been conclusive with respect to the strength and specificity of this association. Therefore, we compared the association of adverse childhood experiences with both hypochondriasis and depression.', 'Fifty-eight patients with hypochondriasis, 52 patients with depression, and 52 healthy control participants completed the Childhood Trauma Questionnaire (CTQ) which assesses 5 varieties of abuse and neglect. A clinical interview (SCID-I) was used to establish DSM-IV diagnoses. Associations between childhood maltreatment, hypochondriasis and depression were estimated by means of analyses of variance and multiple linear regression analyses.', 'In comparison to hypochondriacal and healthy participants, patients with a current depressive disorder reported more emotional abuse as well as more emotional and physical neglect during childhood. Patients with hypochondriasis reported more emotional neglect than healthy individuals. However, when predicting the CTQ trauma types by diagnostic category adjusting for sex and comorbid DSM-IV diagnoses, emotional abuse, emotional neglect, physical abuse, physical neglect, as well as the CTQ total score were significantly associated with depression, but none of the CTQ scores was significantly related to hypochondriasis.",
            "output": [
                "Is childhood maltreatment associated with depression but not with hypochondriasis in later life?"
            ]
        },
        {
            "id": "task847-d8d78aeb9dbb496895a701d50107bd31",
            "input": "Religious involvement may help individuals with chronic medical illness cope better with physical disability and other life changes. We examine the relationships between religiosity, depressive symptoms, and positive emotions in persons with major depression and chronic illness.', '129 persons who were at least somewhat religious/spiritual were recruited into a clinical trial to evaluate the effectiveness of religious vs. secular cognitive behavioral therapy. Reported here are the relationships at baseline between religious involvement and depressive symptoms, purpose in life, optimism, generosity, and gratefulness using standard measures.', 'Although religiosity was unrelated to depressive symptoms (F=0.96, p=0.43) and did not buffer the disability-depression relationship (B=-1.56, SE 2.90, p=0.59), strong relationships were found between religious indicators and greater purpose, optimism, generosity, and gratefulness (F=7.08, p<0.0001).",
            "output": [
                "Is religious involvement associated with greater purpose , optimism , generosity and gratitude in persons with major depression and chronic medical illness?"
            ]
        },
        {
            "id": "task847-9b78fba99cb147e29c1d423182de5311",
            "input": "Complex regional pain syndrome (CRPS) is a painful condition with approximately 50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures, and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety, and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood.', 'The authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus.', 'The authors demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, the authors found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain-derived neurotrophic factor in specific brain regions.",
            "output": [
                "Do brain neuroplastic changes accompany anxiety and memory deficits in a model of complex regional pain syndrome?"
            ]
        },
        {
            "id": "task847-6ad68aa3220443299af809413f8bc29e",
            "input": "To determine the effect of pre-existing maternal obesity and gestational diabetes mellitus (GDM) on the circulating levels of insulin growth factor-binding protein (IGFBPs) in cord and maternal plasma.', 'IGFBP-1-7 levels were measured on maternal and cord plasma from women with normal glucose tolerance (NGT) (30 non-obese and 36 obese) and GDM (44 non-obese and 26 obese) at the time of term elective cesarean section.', 'Maternal plasma IGFBP-1, IGFBP-6 and IGFBP-rP1 concentrations were significantly lower in NGT obese compared with NGT non-obese women and in non-obese GDM women compared with non-obese NGT women. In cord plasma, IGFBP-1-3 and IGFBP-rP1 concentrations were significantly lower in NGT obese compared with NGT non-obese women and in non-obese GDM women compared with non-obese NGT women. Significant positive correlations were observed between maternal and cord plasma IGFBP-1 and IGFBP-rP1 levels and maternal insulin resistance. In cord plasma, significant positive correlations were observed between IGFBP-1-3 and IGFBP-rP1 levels and fetal insulin resistance. Fetal birthweight was inversely correlated with maternal plasma IGFBP-1 levels and cord plasma IGFBP-1 and IGFBP-2 levels. When corrected for maternal body mass index, the only significant relationship that still existed was between cord plasma IGFBP-1 concentrations and fetal birthweight.",
            "output": [
                "Are insulin-like growth factor-binding protein 1 and 7 concentrations lower in obese pregnant women , women with gestational diabetes and their fetuses?"
            ]
        },
        {
            "id": "task847-216968f6e79b474bb28b5e2e701524fe",
            "input": "To investigate the potential role of prostasin, as an invasion suppressor, in the process of trophoblast invasion in preeclampsia.', 'This case-control study included 19 early-onset severe preeclampsia (\u2a7d 34 weeks), 20 late-onset severe preeclampsia (>34 weeks) and 20 normal term pregnant women. Immunohistochemistry was conducted to identify the cellular localization of prostasin, as well as the matrix metalloproteinase 2 (MMP2) and MMP9 in the placenta tissues. Enzyme-linked immunosorbent assay was performed to analyze the expression of these three proteins in placental homogenates. The effect of prostasin on the invasive and migratory ability of trophoblast cells was detected by transwell assays. We also examined the regulation of the prostasin antibody in the MMP2 and MMP9 secretion by HTR-8/SVneo cells via blocking the prostasin activity.', 'This study demonstrated that the prostasin, MMP2 and MMP9 were all expressed in the placental syncytiotrophoblasts. Increased expression of prostasin was detected in cases with early-onset severe preeclampsia compared with the late-onset and control groups (P < 0.05), whereas the expression patterns of MMP2 and MMP9 in placental homogenates were opposite to that of prostasin (P < 0.05). Recombinant prostasin inhibited the invasion and migration of trophoblast cells, whereas prostasin antibody enhanced the MMP2 and MMP9 secretion in a dose- and time-dependent manner.",
            "output": [
                "Does increased expression of prostasin contribute to early-onset severe preeclampsia through inhibiting trophoblast invasion?"
            ]
        },
        {
            "id": "task847-2f30f25b509d4971b99b74330439d21c",
            "input": "There have seen several studies evaluating the efficacy of anti-tumor necrosis factor \u03b1 (anti-TNF\u03b1) compared with conventional therapy (i.e. immunomodulators, mesalamine, or placebo) at preventing postoperative Crohn's disease (CD) recurrence. The results of these studies have been variable and the magnitude by which anti-TNF\u03b1 therapy alters the natural history of CD in the postoperative setting has not yet been fully defined.\", 'A comprehensive search of PubMed/MEDLINE, Scopus, CINAHL, and Cochrane databases was performed (May 2014). All studies on adult patients with CD that compared anti-TNF\u03b1 therapy versus conventional therapy or placebo to prevent CD recurrence were included. Meta-analysis was performed using the Mantel-Haenszel (fixed effects) model with odds ratio (OR) to assess for clinical remission.', 'In the pooled analysis, there was a higher frequency of achieving clinical remission beyond 1 year from time of surgery among patients receiving anti-TNF\u03b1 therapy compared with conventional therapy [OR 6.41; 95% confidence interval (CI) 2.88-14.27]. There was also a significantly higher rate of achieving both endoscopic (OR 26.44; 95% CI 10.48-66.68) and histologic remission (OR 9.80; 95% CI 2.54-37.81) in the anti-TNF\u03b1 therapy group compared with the conventional therapy group.",
            "output": [
                "Is antitumor necrosis factor \u03b1 more effective than conventional medical therapy for the prevention of postoperative recurrence of Crohn 's disease : a meta-analysis?"
            ]
        },
        {
            "id": "task847-b4bca11e36af4279b6b1aa000843cf0b",
            "input": "Critical illness-related corticosteroid insufficiency has been reported in acute variceal bleeding (AVB). In cirrhosis, free serum cortisol (FC) is considered optimal to assess adrenal function. Salivary cortisol (SC) is considered a surrogate for FC. We evaluated FC and its prognostic role in AVB.', \"Total serum cortisol, SC, cortisol-binding globulin, and FC (Coolens' formula) were evaluated in AVB (n=38) and in stable cirrhosis (CC) (n=31). A Cox proportional hazards model was evaluated for 6-week survival.\", 'In AVB, the median FC and SC levels were higher with worse liver dysfunction [Child-Pugh (CP) A/B/C: 1.59/2.62/3.26\\u2009\u03bcg/dl, P=0.019; CPA/B/C: 0.48/0.897/1.81\\u2009\u03bcg/ml, P<0.001, respectively]. In AVB compared with CC, median total serum cortisol: 24.3 versus 11.6\\u2009\u03bcg/dl (P<0.001), SC: 0.86 versus 0.407\\u2009\u03bcg/ml (P<0.001); FC 2.4 versus 0.57\\u2009\u03bcg/dl (P<0.001). In AVB, 5-day rebleeding was 10.5%, and 6-week and total mortality were 21.1 and 23.7%, respectively. Independent associations with 6-week mortality in AVB were FC at least 3.2\\u2009\u03bcg/dl (P<0.001), hepatocellular carcinoma (P<0.001), CPC (P<0.001), and early rebleeding (P<0.001). Among patients with normal cortisol-binding globulin (n=14) and albumin (n=31), the factors were hepatocellular carcinoma (P=0.003), CP (P=0.003), and FC (P=0.036). SC was also found to be an independent predictor of 6-week mortality (P<0.001). Area under the curve of FC for predicting 6-week mortality was 0.79.",
            "output": [
                "Is higher free serum cortisol associated with worse survival in acute variceal bleeding because of cirrhosis : a prospective study?"
            ]
        },
        {
            "id": "task847-c4005bb8eb814c7b9e44a2c013bcb86c",
            "input": "Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease.', 'Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men\u226413, women\u226411 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls.', \"Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172\u00b16\\u2009cm, range 161-182) compared with men with pubertal (179\u00b16\\u2009cm, 161-192) or adult (178\u00b17\\u2009cm, 162-200) age at onset and the general population (178\u00b17\\u2009cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8\u00b10.9) compared with the other patient groups (-0.1\u00b10.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age.",
            "output": [
                "Is early-onset Crohn 's disease a risk factor for smaller final height?"
            ]
        },
        {
            "id": "task847-2cf648685ec94b40a6e1938f77afe1d6",
            "input": "Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes.', 'We used an in vitro coculture system in which UM cell lines and T cells were cultured together, but separated by a membrane. Uveal melanoma gene expression was quantified using a microarray. Protein expression in the supernatant was quantified with ELISA or cytometric bead array. For the monocyte migration assay, a transwell plate was used.', 'Gene-expression analysis of UM cell lines showed that coculture with activated T cells resulted in an upregulation of chemokines such as CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5, VEGF, intracellular adhesion molecule 1 (ICAM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The upregulation of these molecules was confirmed at the protein level. This increase of chemokines coincided with an increased chemotactic capacity of the supernatant toward monocytes.",
            "output": [
                "Does inflammation-induced chemokine expression in uveal melanoma cell lines stimulate monocyte chemotaxis?"
            ]
        },
        {
            "id": "task847-c349cf2b5969473daaee7e5e77efee82",
            "input": "Hirschsprung's disease is characterized by a developmental arrest of neural crest cell migration, causing distal aganglionosis. Transplanted cells derived from the neural crest may regenerate enteric ganglia in this condition. We investigated the potential of skin-derived precursor cells (SKPs) to engraft and to differentiate into enteric ganglia in aganglionic rat intestine in vivo.\", 'Adult Lewis rat jejunal segments were separated from intestinal continuity and treated with benzalkonium chloride to induce aganglionosis. Ganglia were identified via immunohistochemical stains for S100 and \u03b2-III tubulin (TUJ1). SKPs were procured from neonatal Lewis rats expressing enhanced green fluorescent protein (GFP) and cultured in neuroglial-selective media. SKP cell line expansion was quantified, and immunophenotypes were assessed by immunocytochemistry. Aganglionic segments underwent SKP transplantation 21-79days after benzalkonium chloride treatment. The presence of GFP+cells, mature neurons, and mature glia was evaluated at posttransplant days 1, 6, and 9.', 'Benzalkonium chloride-induced aganglionosis persisted for at least 85days. Prior to differentiation, SKPs expressed S100, denoting neural crest lineage, and nestin, a marker of neuronal precursors. Differentiated SKPs in vitro expressed GFAP, a marker of glial differentiation, as well as TUJ1 and several enteric neurotransmitters. After transplantation, GFP+structures resembling ganglia were identified between longitudinal and circular smooth muscle layers.",
            "output": [
                "Do transplanted skin-derived precursor stem cells generate enteric ganglion-like structures in vivo?"
            ]
        },
        {
            "id": "task847-d2a14c59b7b549c58aad13f223e922e2",
            "input": "Headache is a common complaint for emergency visits. Common drugs used in relief of headache are opioids and their agonists and antagonists, ergot alkaloids, and nonsteroidal anti-inflammatory drugs (NSAIDs). Lack of appropriate medications or serious side effects of available drugs, motivated us to perform the study for evaluating the efficacy of intranasal lidocaine on different types of headache.', \"A double-blind, randomized clinical trial (RCT) was performed among 90 adult patients with acute headache in Shahid Rahnemoon Emergency Center of Yazd city of Iran (45 patients in lidocaine group and 45 patients in placebo group). Patients with history of epilepsy, allergy to lidocaine, signs of skull base fracture, Glasgow Coma Scale (GCS) < 15, patients younger than 14 years and patients who had received any medication in previous 2 h were excluded. After checking vital signs and taking the demographic data, one puff of 10% lidocaine or normal saline (placebo) was sprayed into each nostril. Patients' headache severity measured by visual analog scale (VAS) before drug administration and at 1, 5, 15, and 30 min after intervention. Data were analyzed by Statistical Package for Social Sciences (SPSS) version 17 and statistical tests including t-test, repeated measures analysis of variance (ANOVA), Fisher's exact test, and Mann-Whitney test were performed. Descriptive variables were expressed by mean \u00b1 standard deviation (SD) and quantitative variables reported by frequency and percentages. P-values less than 0.05 were considered significant.\", '57.8% of patients were female. The mean age of patients was 35.32 years. According to sex and age, there was no significant difference between groups (P-values were 0.83 and 0.21; respectively). The mean base pain score was 6.97 in lidocaine group and 6.42 in placebo group which was not significantly different (P-value = 0.198). After intervention, the mean scores were significantly lower in lidocaine group than placebo group in all mentioned times (P-value < 0.001). The primary and secondary headaches had no significant difference in mean pain relief score in lidocaine group (P = 0.602).",
            "output": [
                "Do evaluation of efficacy of intra-nasal lidocaine for headache relief in patients refer to emergency department?"
            ]
        },
        {
            "id": "task847-e91a8e60304f48edb3c86a6faf744fcf",
            "input": "To evaluate whether core length impacts biopsy accuracy and Gleason score underestimation compared to radical prostatectomy (RP) specimens.', 'From 2010 to 2011, 8,928 cores were trans-rectal obtained from 744 consecutive patients (178 RP, 24%), 557 by an experienced performer (>250/year) and 187 (25%) by in-training urology residents. Prospectively analyzed variables were core length, age, prostate volume, free and total prostate-specific antigen (PSA), PSA density and free/total PSA ratio.', 'Mean core length for Gleason upgrading on RP (42.7%, n = 76) was 11.61 (\u00b12.5, median 11.40) compared to 13.52 (\u00b13.2, median 13.70), p < 0.001 for perfect biopsy-RP Gleason agreement (57.3%, n = 102). In multivariate analysis, for each unit of core length increment in millimeter, the Gleason upgrading risk decreased 89.9%, p = 0.049 [odds ratio (OR) 0.10, 95% confidence interval (CI) 0.01-0.99]. Biopsy positivity between experienced (35.5%) and in-training performer (30.1%) was not significantly different (p = 0.20), with comparable mean patient age (65.1 vs. 64.1), prostate volume (52.3 vs. 50.7) and median PSA (5.2 vs. 5.1), respectively. Denoting wider variability in terms of core length, in-training performers obtained significantly larger cores for positive biopsies (11.33 \u00b1 3.42 vs. 10.83 \u00b1 3.68), p = 0.043, compared to experienced performer (11.39 \u00b1 3.36 vs. 11.37 \u00b1 3.64), p = 0.30. In multivariate analysis, PSA density (OR 1.14, 95% CI 1.02-1.28) and age (OR 1.04, 95% CI 1.01-1.07) were significantly associated with biopsy positivity, p = 0.021 and p = 0.011, respectively.",
            "output": [
                "Is gleason underestimation predicted by prostate biopsy core length?"
            ]
        },
        {
            "id": "task847-d83be89bb19d40d88a93a532dbbe786d",
            "input": "To determine whether PTEN status in prostate biopsy represents a predictor of intermediate and long-term oncological outcomes after radical prostatectomy, and whether PTEN status predicts response to androgen deprivation therapy.', 'In a retrospective analysis of 77 men treated by radical prostatectomy who underwent diagnostic biopsy between 1992-2006, biopsy samples were stained for PTEN expression by the PREZEON assay with >10% staining reported as positive. Cox proportional hazards and log-rank models were used to assess the correlation between PTEN loss and clinical outcomes.', 'During a median follow-up period after radical prostatectomy of 8.8 years, 39 men (51%) developed biochemical recurrence, four (5%) had castration-resistant prostate cancer, two (3%) had metastasis and two (3%) died from prostate cancer. PTEN loss was not significantly associated with biochemical recurrence (hazard ratio 2.1, 95% confidence interval 0.9-5.1, P = 0.10), but significantly predicted increased risk of castration-resistant prostate cancer, metastasis and prostate cancer-specific mortality (all log-rank, P < 0.0001), and time from androgen deprivation therapy to castration-resistant prostate cancer (log-rank, P = 0.003). No patient without PTEN loss developed metastases or died from prostate cancer.",
            "output": [
                "Does pTEN loss in biopsy tissue predict poor clinical outcomes in prostate cancer?"
            ]
        },
        {
            "id": "task847-5459aa026c5149d19e8cc037ce7f106d",
            "input": "Loading otoprotective drug into cochlear implant might change its mechanical properties, thus compromising atraumatic insertion. This study evaluated the effect of incorporation of dexamethasone (DXM) in the silicone of cochlear implant arrays on insertion forces.', 'Local administration of DXM with embedded array can potentially reduce inflammation and fibrosis after cochlear implantation procedure to improve hearing preservation and reduce long-term impedances.', 'Four models of arrays have been tested: 0.5-mm distal diameter array (n = 5) used as a control, drug-free 0.4-mm distal diameter array (n = 5), 0.4-mm distal diameter array with 1% eluded DXM silicone (n = 5), and 0.4-mm distal diameter array with 10% eluded DXM silicone (n = 5). Via a motorized insertion bench, each array has been inserted into an artificial scala tympani model. The forces were recorded by a 6-axis force sensor. Each array was tested seven times for a total number of 140 insertions.', 'During the first 10-mm insertion, no difference between the four models was observed. From 10- to 24-mm insertion, the 0.5-mm distal diameter array presented higher insertion forces than the drug-free 0.4-mm distal diameter arrays, with or without DXM. Friction forces for drug-free 0.4-mm distal diameter array and 0.4-mm distal diameter DXM eluded arrays were similar on all insertion lengths.",
            "output": [
                "Do effect of embedded dexamethasone in cochlear implant array on insertion forces in an artificial model of scala tympani?"
            ]
        },
        {
            "id": "task847-5c8ab5e61da449e497280bccdf8a08ee",
            "input": "Both diet quality (DQ) and physical activity (PA) have been shown to play a role in the prevention of functional capacity (FC) decline. Because older adults (OA) with T2D are at a higher risk of FC decline compared to their non-diabetic counterparts, our aim was to determine if DQ alone, or combined with PA is associated with FC decline in OA with T2D over a 3-year follow-up in a secondary analysis of the NuAge cohort.', \"In 159 OA with T2D (mean age=75 years), FC change was calculated as the difference in FC scores at T1 and T4 measured by the SMAF (Syst\u00e8me de Mesure de l'Autonomie Fonctionnelle). Baseline DQ was calculated from three non-consecutive 24-h dietary recalls collected at T1 using the validated Canadian Healthy Eating Index (C-HEI). PA change was calculated from Physical Activity Scale for the Elderly (PASE) as T4-T1. Associations were evaluated between FC decline and four combinations of variables: C-HEI score < or \u226570 with PASE change < or > median and analyzed by GLM while controlling for covariates.\", 'Neither DQ alone nor DQ combined with PA change were associated with FC decline over follow-up.",
            "output": [
                "Is decline in functional capacity unaffected by diet quality alone or in combination with physical activity among generally healthy older adults with T2D from the NuAge cohort?"
            ]
        },
        {
            "id": "task847-e650b82cd18d47559088a74fcd120f48",
            "input": "Thrombocytopenia is a common complication in malaria patients. The relationship between abnormal platelet profile and clinical status in malaria patients is unclear. In low and unstable endemic regions where vivax malaria predominates, the hematologic profiles of malaria patients and their clinical utility are poorly understood. The aim of this study was to characterize the thrombograms of malaria patients from Colombia, where Plasmodium vivax infection is common, and to explore the relationship between thrombograms and clinical status.', 'Eight hundred sixty-two malaria patients were enrolled, including 533 (61.8%) patients infected with Plasmodium falciparum, 311 (36.1%) patients infected with Plasmodium vivax and 18 (2.1%) patients with mixed infections.', 'The most frequently observed changes were low platelet count (PC) and high platelet distribution width (PDW), which were observed in 65% of patients; thrombocytopenia with <50,000 platelets/\u00b5L was identified in 11% of patients. Patients with complications had lower PC and plateletcrit (PT) and higher PDW values. A higher risk of thrombocytopenia was identified in patients with severe anemia, neurologic complications, pulmonary complications, liver dysfunction, renal impairment and severe hypoglycemia. The presence of thrombocytopenia (<150,000 platelets/\u00b5L) was associated with a higher probability of liver dysfunction.",
            "output": [
                "Is platelet profile associated with clinical complications in patients with vivax and falciparum malaria in Colombia?"
            ]
        },
        {
            "id": "task847-6d6afb4ad79a4df68a91f0ab4df18a41",
            "input": "The aim of this study was to determine whether the diagnostic yield of thyroid fine-needle aspirations (FNAs) changes over the course of residency training.', 'We identified 5418 ultrasound-guided thyroid nodule FNAs performed in our radiology department from 2004 through 2012. For each FNA, we recorded if the FNA was performed by a resident and if so the name of the resident and supervising attending radiologist. For each resident, we determined the level of training based on their graduation year from our residency program and the date of the FNA as well as prior surgical training and if they completed subsequent interventional radiology fellowship. Pathology reports were reviewed, and FNAs were classified as diagnostic or nondiagnostic (ND). Generalized mixed models were used to assess ND rate with postgraduate years, including residents with and without prior surgical training or if they subsequently completed an interventional radiology fellowship.', 'Of the 5418 thyroid FNAs, 3164 (58.4%) were performed by a radiology resident under the direct supervision of an attending physician. There was a significant decrease in ND rate as postgraduate years increased (P < .05). A significant decrease in ND rate was found as postgraduate years increased for residents without prior surgical training (P = .0007) or subsequent training in interventional radiology (P = .0014); however, no significant decrease was found for residents with surgical training (P = .37) or completing an interventional radiology fellowship (P = .08). In addition, no significant difference was found for ND rate between postgraduate year 4 (PGY4) and PGY5 (P > .05).",
            "output": [
                "Does resident experience increase diagnostic rate of thyroid fine-needle aspiration biopsies?"
            ]
        },
        {
            "id": "task847-fc0cd3c06c964d41ad53865457d80987",
            "input": "After myocardial infarction (MI), baroreflex function is impaired and heart rate (HR) variability is reduced. An impaired baroreflex has been observed also in coronary patients with no previous MI, leading to hypothesize alterations of HR variability also in these patients. The aim of the present work was, therefore, to study whether and to what extent cardiovascular variability is altered in coronary patients with no previous MI.', 'Thirty-two individuals were studied: eleven patients with coronary artery disease but no previous MI [coronary artery disease (CAD)], eleven patients with a reduced left ventricular ejection fraction [congestive heart failure (CHF)] and ten age-matched controls (CNT).', 'Overall HR variability was significantly and similarly reduced in CAD (630\\u200a\u00b1\\u200a272\\u200ams) and CHF patients (594\\u200a\u00b1\\u200a395\\u200ams) with respect to CNT (1405\\u200a\u00b1\\u200a837\\u200ams), this being the case also for the low and high frequency spectral components. Low-frequency oscillations of blood pressure (BP) were also significantly and similarly less pronounced in CAD (0.7\\u200a\u00b1\\u200a0.7\\u200ammHg) and CHF patients (0.7\\u200a\u00b1\\u200a0.7\\u200ammHg) compared with CNT (1.8\\u200a\u00b1\\u200a1.4\\u200ammHg). Moreover, both CAD and CHF patients showed a significantly reduced baroreflex function and an increased pulse-wave velocity with respect to CNT.",
            "output": [
                "Is cardiovascular variability similarly altered in coronary patients with normal left ventricular function and in heart failure patients?"
            ]
        },
        {
            "id": "task847-afaecc1ff1214ca69ce66a1fa670376e",
            "input": "Advanced glycation end products (AGE) are involved in the progression of diabetic complications. Although our previous reports show that AGE increased dental pulp calcification, AGE accumulation is also associated with inflammation. This study examined AGE effect on the expression of inflammation factors using rat dental pulp tissues and cell cultures.', 'Receptor for AGE (RAGE), S100A8, S100A9, and interleukin (IL)-1\u03b2 were selected as inflammation parameters. Rat dental pulp cells were cultured and treated with AGE, and the effects were determined by real-time PCR. An anti-RAGE antibody or MAPK pathway inhibitors (PD98059, SB203580, and SP60012) were used to investigate AGE signaling pathway.', 'The mRNA levels of RAGE, S100A8, S100A9, and IL-1\u03b2 were higher in diabetic pulp tissues. AGE increased mRNA expressions of S100A8, S100A9, and IL-1\u03b2 in cultured dental pulp cells. In the presence of anti-RAGE antibody, AGE did not increase in S100A8 or S100A9 expressions. The AGE-induced increases in S100A8 and S100A9 were inhibited by PD98059 and SB203580, respectively.",
            "output": [
                "Do advanced glycation end products increase expression of S100A8 and A9 via RAGE-MAPK in rat dental pulp cells?"
            ]
        },
        {
            "id": "task847-8e370c3e67544864ae185d2f52c73dbb",
            "input": "To assess whether zoledronic acid (ZOL) adds to the effect of combined androgen blockade (CAB) in patients with hormone-naive bone metastatic prostate cancer.', 'Patients were treated with either a combination of CAB (luteinizing hormone-releasing hormone agonist and bicalutamide) and ZOL (CAB-Z group) or CAB-alone (historical control patients, CAB-C group). ZOL was injected intravenously at 4 mg every 4 weeks. One hundred and five and 100 patients among 205 enrolled patients were assigned to the CAB-Z group and CAB-C group, respectively. The time to prostate-specific antigen (PSA) failure in patients in the CAB-Z group was compared to that in the CAB-C group. The primary end-point of the study was the time-to-PSA failure.', 'PSA and serum N-telopeptide of type I collagen (NTx) levels were examined before treatment and every 3 months after treatment. PSA failure occurred in 42 (40.0%) patients in the CAB-Z group and 48 (48.0%) patients in the CAB-C group. The biochemical recurrence-free rate was significantly lower in patients in the CAB-C group (p=0.004, by log-rank test). The categorical biopsy Gleason score pre-treatment serum NTx and treatment with ZOL were shown to be independent predictors of PSA failure-free survival time (p=0.040, p=0.005 and p=0.026, respectively).",
            "output": [
                "Does zoledronic acid improve clinical outcomes in patients with bone metastatic hormone-na\u00efve prostate cancer in a multicenter clinical trial?"
            ]
        },
        {
            "id": "task847-c85cd5abb6ac464db2f0013bcb0310ec",
            "input": "Evaluate the effect of a anterior cruciate ligament injury prevention program coaching workshop on elite-level youth soccer coaches' behavioral determinants to implement a injury prevention program and describe coaches' subsequent injury prevention program implementation compliance.\", 'Descriptive study.', \"We evaluated a soccer club's coaches' behavioral determinants regarding injury prevention programming implementation before and after a coaching workshop using pre- and post-workshop surveys. We then described the club's coaches' subsequent adoption of and implementation compliance with the injury prevention programming during the following season.\", \"The injury prevention workshop increased coaches' attitudes toward conducting a program at the beginning of practice (p<0.05), substituting the program for a warm-up prior to practice (p<0.05), and improving player cutting and landing technique by implementing the program (p<0.05). The injury prevention program workshop increased coaches' perceived behavioral control; feeling more comfortable in their ability to teach their team a program (p<0.05), and more confident leading a program if given instructions (p<0.05). The injury prevention program workshop increased coaches' intent to implement a program the next season (p<0.05), to implement a program for 15min (p<0.05), and 20min (p<0.05) prior to the start of a training session. Only 53% of the club's teams implemented the injury prevention program, with implementers demonstrating high variability in program fidelity.",
            "output": [
                "Does high levels of coach intent to integrate a ACL injury prevention program into training translate to effective implementation?"
            ]
        },
        {
            "id": "task847-5f64986e96ed4f11ba2c9b4033108e17",
            "input": "Behavioral measures of cochlear implant (CI) device stimulation levels can be difficult to obtain in individuals with limited or no hearing experience. Loudness measures are particularly challenging. It would therefore be useful to have a battery of objective and behavioral measures to determine CI stimulation levels in listeners with childhood deafness. In the present study, the authors characterized loudness growth in 20 adolescents: 8 with normal hearing and 12 CI participants with pre/perilingual bilateral sensorineural hearing loss. They asked (1) do adolescent CI users with childhood deafness experience similar increases in loudness as their peers with normal hearing? and (2) can loudness be predicted by objective measures of auditory activity? The authors hypothesized that loudness perception would be significantly different between CI and normal-hearing groups and that it would correlate with objective measures.', \"CI users were recruited from the Cochlear Implant Program at The Hospital for Sick Children and all had used unilateral Nucleus CIs for at least 2 years. The dynamic range for each participant was defined as the difference between the behavioral threshold and the electrically evoked stapedius reflex (ESR) threshold. Loudness growth was assessed within this range behaviorally on a continuous visual scale and objectively with physiological measures. Auditory brainstem responses (ABRs) and ESRs were recorded in both groups and electrically evoked compound action potentials (ECAPs) of the auditory nerve were recorded in addition in CI listeners. The regression line slopes of ECAP and ABR amplitude growth functions were then calculated and compared with behavioral loudness growth slopes in the upper portion (40-100%) and lower portion (0-40%) of the dynamic range. Electrical pulse stimuli (in CI users) and acoustic clicks (in normal-hearing participants) were presented within each participant's dynamic range.\", 'The mean dynamic range in CI listeners was more variable than in normal-hearing individuals. Despite this difference, loudness at the ESR threshold was not significantly different in CI adolescents from their normal-hearing peers, and CI users exhibited normal-like loudness growth. There was a significantly positive correlation between ECAP amplitude growth and loudness growth in CI users in the upper portion of the dynamic range, while ABR wave V amplitude growth was not related to loudness growth in either group.",
            "output": [
                "Do unilateral cochlear implant use promotes normal-like loudness perception in adolescents with childhood deafness?"
            ]
        },
        {
            "id": "task847-1424e117a54f418eb8510dcc6a9f423f",
            "input": "Hearing loss is a commonly experienced disability in a variety of populations including veterans and the elderly and can often cause significant impairment in the ability to understand spoken language. In this study, we tested the hypothesis that neural and behavioral responses to speech will be differentially impaired in an animal model after two forms of hearing loss.', 'Sixteen female Sprague-Dawley rats were exposed to one of two types of broadband noise which was either moderate or intense. In nine of these rats, auditory cortex recordings were taken 4 weeks after noise exposure (NE). The other seven were pretrained on a speech sound discrimination task prior to NE and were then tested on the same task after hearing loss.', 'Following intense NE, rats had few neural responses to speech stimuli. These rats were able to detect speech sounds but were no longer able to discriminate between speech sounds. Following moderate NE, rats had reorganized cortical maps and altered neural responses to speech stimuli but were still able to accurately discriminate between similar speech sounds during behavioral testing.",
            "output": [
                "Does behavioral and neural discrimination of speech sound after moderate or intense noise exposure in rats?"
            ]
        },
        {
            "id": "task847-4043e5ca8dde453982b0737e32b6d526",
            "input": "1,8-Cineole, the main monoterpene in many essential oils, has been used as an ingredient in flavourings and medicine. 1,8-Cineole has been shown to possess pharmacological properties, including anti-oxidative, anti-inflammatory and anti-nociceptive actions. However, to date, no studies have examined the potential of 1,8-cineole to protect against cerebral ischaemic injury.', 'In this study, we investigated the neuroprotective effects of 1,8-cineole against cortical neuronal/glial cell injury caused by oxygen-glucose deprivation/reoxygenation (OGD/R) in an in-vitro model of ischaemia.', '1,8-Cineole significantly attenuated OGD/R-induced cortical cell injury, as well as reduced n-methyl-d-aspartate (NMDA)-induced cell injury. However, it did not inhibit NMDA-induced cytosolic calcium overload. Nevertheless, 1,8-cineole significantly reduced the OGD/R- and NMDA-induced overproduction of reactive oxygen species (ROS). These results indicate that 1,8-cineole exerts neuroprotection through its anti-oxidative rather than its anti-excitotoxic, properties. The decrease in OGD/R-induced intracellular superoxide in 1,8-cineole-treated cortical cells was associated with the upregulation of superoxide dismutase activity. Moreover, 1,8-cineole showed direct ROS scavenging activity in an assay of oxygen radical absorbance capacity.",
            "output": [
                "Does 1,8-Cineole ameliorate oxygen-glucose deprivation/reoxygenation-induced ischaemic injury by reducing oxidative stress in rat cortical neuron/glia?"
            ]
        },
        {
            "id": "task847-1d83e46772854a6db1c3aa84760fc0bd",
            "input": "Dynamic pelvic magnetic resonance imaging (DP-MRI) offers a comprehensive evaluation of pelvic organ structure in addition to functional information regarding evacuation. Opportunity to apply this technology can be limited due to regional lack of availability. Ideally, clues from standard anorectal testing could predict abnormalities on DP-MRI, leading to its efficient use. The aim of this study is to determine whether high-resolution anorectal manometry (HR-ARM) correlates with findings on DP-MRI.', \"This is a retrospective study of HR-ARM performed on patients with constipation who also underwent DP-MRI. Studies were reviewed for significant findings including posterior pelvic organ prolapse, rectocele\\u2009>\\u20093\\u2009cm, rectal intussusception, and anorectal angle. Statistical analysis was performed using Pearson's correlation coefficient, Student's t-test, and Fisher's exact test.\", 'Twenty-three patients undergoing HR-ARM (age range 25-78) also underwent DP-MRI. All were female; 76% were Caucasian. Twenty had significant structural findings: small pelvic prolapse (n\\u2009=\\u20092), moderate pelvic prolapse (n\\u2009=\\u200910), large pelvic prolapse (n\\u2009=\\u20099), rectocele (n\\u2009=\\u20098), or rectal intussusception (n\\u2009=\\u20093). Only intrarectal pressure on HR-ARM weakly correlated with size of rectocele (r\\u2009=\\u20090.46; P\\u2009=\\u20090.03) and degree of pelvic organ prolapse (r\\u2009=\\u20090.48; P\\u2009=\\u20090.02). The remainder of the HR-ARM parameters did not significantly correlate with DP-MRI findings. Patients with dyssynergy were not more likely to have rectoceles\\u2009>\\u20093\\u2009cm (44.4% versus 35.7%; P\\u2009=\\u20090.5) or large prolapses (44.4% versus 50%, P\\u2009=\\u20091.0), compared with those without dyssynergy, on HR-ARM.",
            "output": [
                "Are high-resolution anorectal manometry and dynamic pelvic magnetic resonance imaging complementary technologies?"
            ]
        },
        {
            "id": "task847-4e6ac1477ed449148d854c48fd7356e6",
            "input": "Recognising colorectal cancer (CRC) patients with Lynch syndrome (LS) can increase life expectancy of these patients and their close relatives. To improve identification of this under-diagnosed disease, experts suggested raising the age limit for CRC tumour genetic testing from 50 to 70 years. The present study evaluates the efficacy and cost-effectiveness of this strategy.', 'Probabilistic efficacy and cost-effectiveness analyses were carried out comparing tumour genetic testing of CRC diagnosed at age 70 or below (experimental strategy) versus CRC diagnosed at age 50 or below (current practice). The proportions of LS patients identified and cost-effectiveness including cascade screening of relatives, were calculated by decision analytic models based on real-life data.', 'Using the experimental strategy, four times more LS patients can be identified among CRC patients when compared with current practice. Both the costs to detect one LS patient (\u20ac9437/carrier versus \u20ac4837/carrier), and the number needed to test for detecting one LS patient (42 versus 19) doubled. When family cascade screening was included, the experimental strategy was found to be highly cost-effective according to Dutch standards, resulting in an overall ratio of \u20ac2703 per extra life-year gained in additionally tested patients.",
            "output": [
                "Is fourfold increased detection of Lynch syndrome by raising age limit for tumour genetic testing from 50 to 70 years cost-effective?"
            ]
        },
        {
            "id": "task847-13512759169646129d56b72cbcbc6d11",
            "input": "Early diagnosis is important in preventing mortality from malaria. The hypothesis that guardians' fear of covert human immunodeficiency virus (HIV) testing delays presentation of children with suspected malaria was tested.\", \"The study design is a cross-sectional survey. The study population consisted of guardians of children with suspected malaria who presented to health centres in Oromia Region, Ethiopia. Data were collected on attitudes to HIV testing and the duration of children's symptoms using interview administered questionnaires.\", 'Some 830 individuals provided data representing a response rate of 99% of eligible participants. Of these, 423 (51%) guardians perceived that HIV testing was routinely done on blood donated for malaria diagnosis, and 353 (43%) were aware of community members who delayed seeking medical advice because of these concerns. Children whose guardians suspected that blood was covertly tested for HIV had longer median delay to presentation for evaluation at health centres compared to those children whose guardians did not hold this belief (three days compared to two days, p < 0.001). Children whose guardians were concerned about covert HIV testing were at a higher odds of a prolonged delay before being seen at a health centre (odds ratio 1.73, 95% confidence intervals: 1.10 to 270 for a delay of \u2265 3 days compared to those seen in \u2264 2 days).",
            "output": [
                "Are concerns about covert HIV testing associated with delayed presentation of suspected malaria in Ethiopian children : a cross-sectional study?"
            ]
        },
        {
            "id": "task847-f689d4d570d2408cbe30a42efce99612",
            "input": "Fractional CO2 laser has recently emerged as a promising therapeutic modality to improve the texture and appearance of burn scars. An issue in many burn scars is persistent erythema, which traditionally has been treated with vascular lasers. Interestingly, fractional CO2 lasers have been shown to improve the appearance of burn scars, including erythema, but no mechanism has been proposed for this change. Our objective is to evaluate the histopathologic changes in vasculature in burn scars treated with fractionated CO2 laser, and to attempt to describe the mechanism behind reduced erythema following treatment.', 'Uncontrolled, prospective study of ten patients with mature burn scars, from a clinical and histological perspective. Biopsy specimens were obtained before and 2 months after 3 treatment sessions. Anti-CD31 immunostaining was performed to highlight vascular patterns in biopsy specimens.', 'In histological analysis, an increase in vascular density, particularly of small caliber vessels, was seen following treatment, with an 82.6% average increase in vasculature (P\\u2009=\\u20090.028). This increase in vascularity correlated with a decrease in clinical erythema and vascularity scores, measured using the Vancouver Scar Scale.",
            "output": [
                "Do vascular patterns in mature hypertrophic burn scars treated with fractional CO2 laser?"
            ]
        },
        {
            "id": "task847-539804acfa494836bfc6f184a9c0246b",
            "input": "Annual seasonal and pandemic influenza vaccines need to be produced in a very tight time frame. Haemagglutinin (HA) is the major immunogenic component of influenza vaccines, and there is a lot of interest in improving candidate vaccine viruses.', \"It has been shown elsewhere that mutations introduced in the non-coding region of influenza genome segments can upregulate protein expression. Our objective was to assess a virus based on the laboratory strain A/PR/8/34 (PR8) containing a modified 3' non-coding region of RNA segment 4 (haemagglutinin).\", 'NIBRG-93 was generated using reverse genetics. HA protein expression and growth properties were assessed. The virus phenotype suggested that it could be a candidate for use as a live attenuated vaccine, so in vivo studies were performed to assess its suitability.', \"NIBRG-93 virus has enhanced haemagglutinin production and is significantly attenuated. Electron microscopy (EM) shows that the modified virus produces a large proportion of 'virus-like particles' that consist of budded cell membrane covered in HA but lacking M1 protein. The virus was shown to be attenuated in mice and offered complete protection against lethal challenge.",
            "output": [
                "Does a promoter mutation in the haemagglutinin segment of influenza A virus generate an effective candidate live attenuated vaccine?"
            ]
        },
        {
            "id": "task847-6f656d6207b148eaa47725c4393f8dae",
            "input": "Obesity adversely inhibits antibody response to vaccination. Three doses of HPV4 may or may not provide adequate long term protection against HPV 16/18 in obese females. The aim of this study was to determine whether adherence to HPV4 vaccination in a safety net population was reduced with increasing body mass index (BMI).', 'We designed a historical prospective study evaluating the number and dates of HPV4 dosing that occurred from July 1, 2006 through October 1, 2009 by the demographic characteristics of the 10-26 year old recipient females. The defined dosing intervals were adapted from the literature and obesity categories were defined by the WHO.', '1240 females with BMI measurements received at least one dose of HPV4; 38% were obese (class I, II and III) and 25% were overweight. Females with normal BMI received on-time triplet dosing significantly more often than did the obese class II and III females (30% vs. 18%, p<0.001). Obese class II/III females have a significant 45% less chance of completing the on-time triplet HPV4 series than normal women (OR\\u200a=\\u200a0.55, 95% CI: 0.37, 0.83). Pregnancy history has a significant influence on BMI and HPV4 dosing compliance in this safety net population where 71% had been gravid. Hispanic females were less likely to complete HPV4 dosing regardless of BMI (aOR\\u200a=\\u200a0.39, 95% CI: 0.16, 0.95).",
            "output": [
                "Does in a safety net population HPV4 vaccine adherence worsen as BMI increases?"
            ]
        },
        {
            "id": "task847-d91be8014dcf46dd94a7410554d787d2",
            "input": "The membrane protein CD46, a ubiquitous cell surface pathogen receptor, can bind Streptococcus to trigger cell autophagy, which is a critical step in the control of infection.', 'In this study, we found a new splice variant designated CD46 transcript variant (CD46-TV). The splice variant is characterized by the retention of a 48\\xa0bp sequence from intron 8 of the bovine CD46 gene, which encodes a putative protein enlarged by 16 amino acids. CD46-TV mRNA was found to be over expressed in mastitis-infected mammary gland tissues relative to healthy tissues. A single nucleotide polymorphism (c. 1033\\u2009+\\u20092184 C\\u2009>\\u2009T) in the exonic splicing enhancer (ESE) motif region was shown to result in the CD46-TV aberrant splice variant through constructing alternative alleles using the pSPL3 exon capturing vector and transfecting these into 293\\xa0T cells. Allelic frequency in 56,682 individuals belonging to 112 Bos taurus, Bos indicus, Bos javanicus, Bos grunniens and Bos mutus, etc. suggests that the C allele (80.09%) is the ancestral allele. Association analysis found that the mean genomic estimated breeding values (gEBV) for milk somatic cell score and the occurrence of clinical mastitis, as well as the milk somatic cell score of Chinese Holsteins with the CT genotype was lower than those of individuals with either the CC or TT genotypes. The mean gEBV for udder health synthesis for the TT genotype was greater than those for the CC or CT genotypes.",
            "output": [
                "Does a SNP in intron 8 of CD46 cause a novel transcript associated with mastitis in Holsteins?"
            ]
        },
        {
            "id": "task847-d006a40b9b6c4e27b14ba838e8d7cb08",
            "input": "Residual disease (RD) at definitive resection of incidental gallbladder cancer (IGBCA) influences outcome, but its clinical relevance with respect to anatomic site is incompletely characterized.', 'Consecutive patients with IGBCA undergoing re-exploration from 1998 to 2009 were identified; those submitted to a complete resection were analyzed. Demographics and tumor- and treatment-related variables were correlated with RD and survival. Cancer-specific survival was stratified by site of RD (local [gallbladder bed]; regional [bile duct, lymph nodes]; distant [discontiguous liver, port site, peritoneal]).', 'Of the 135 patients submitted to re-exploration, RD was found in 82 (61%) overall and in 63 (54%) of 116 patients submitted to resection; the most common site was regional (n\\xa0=\\xa027, 43%). The T stage of the gallbladder specimen was the only independent predictor of RD (T1b\\xa0= 35.7%, T2\\xa0= 48.3%, T3\\xa0= 70%, p\\xa0= 0.015). The presence of RD at any site dramatically reduced median disease-free survival (DFS) (11.2 vs 93.4 months, p < 0.0001) and disease-specific survival (DSS) (25.2 months vs not reached, p < 0.0001) compared with no RD, respectively. Disease-specific survival did not differ according to RD location, with all anatomic sites being equally poor (p\\xa0= 0.87). Residual disease at any site predicted DFS (hazard ratio [HR] 3.3, 95% CI 1.9 to 5.7, p\\xa0= 0.0003) and DSS (HR 2.4, 95% CI 1.2 to 4.6, p\\xa0= 0.01), independent of all other tumor-related variables.",
            "output": [
                "Does residual disease predict outcomes after definitive resection for incidental gallbladder cancer?"
            ]
        },
        {
            "id": "task847-1ec4af13d9c8420ca02c50170215db90",
            "input": "Weight-loss is a near societal obsession and many diet programs use significant calorie restriction including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24\\u2009h fast and how fasting might generate this effect.', 'Mice were allowed ad libitum access to food or had food withheld for 24\\u2009h. Expression of the endogenous IL-1 antagonists, IL-1 receptor type 2 (IL-1R2), and IL-1 receptor antagonist (IL-1RA) was determined as were sickness behaviors before and after IL-1\u03b2 administration.', 'Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver) and IL-1RA (68-fold in liver). Fasted mice were protected from IL-1\u03b2-induced weight-loss, hypoglycemia, loss of locomotor, and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1\u03b2 on IL-1R2 gene expression in adipose tissue and liver (2.6- and 1.6-fold, respectively). Fasting not only increased IL-1RA and IL-1R2 protein 2.5- and 3.2-fold, respectively, in liver but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs) and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14- and 11-fold, respectively.",
            "output": [
                "Does fasting induce IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL-1R2 and IL-1RA?"
            ]
        },
        {
            "id": "task847-50a0122a305c4da48499306410096707",
            "input": "Aurora kinase A (AurkA) is over-expressed in melanoma and its inhibition has been observed to limit tumor growth, suggesting a potential role in melanoma treatment.', 'A human melanoma cell line with the B-RAF (V600E) mutation (A375mel) was exposed to B-RAF inhibitor (GSK2118436), MEK inhibitor (GSK1120212) and AurkA inhibitor (MLN8054) as single agents or in various combinations (BRAF plus AurkA inhibitor, MEK plus AurkA inhibitor or triple combination BRAF plus MEK plus AurkA inhibitor). Cell proliferation was assessed using xCELLigence technology. Total protein extracts were examined for p53 and c-Myc protein expression by Western blot analysis. Drug anti-tumor effects were further assessed using a 3D-human melanoma skin reconstruction model, in which tissues were incubated with serum-free medium containing control, B-RAF plus MEK inhibitor, MEK plus AurkA inhibitor or the triple combination.', 'AurkA inhibitor plus B-RAF inhibitor, AurkA inhibitor plus MEK inhibitor or triple combination had a markedly greater anti-proliferative effect on A375 (BRAFV600E) melanoma cells than single agents. In the 3D human skin model, the triple combination had a greater anti-tumor effect at the epidermal/dermal junction than control or either double combination. However, S-100 and Ki-67 positively stained spindle-shaped cells were detected in the dermal stratum, suggesting the presence of alive and proliferating melanoma cells.",
            "output": [
                "Do aurkA inhibitors enhance the effects of B-RAF and MEK inhibitors in melanoma treatment?"
            ]
        },
        {
            "id": "task847-453f62311cae48608c28e6ee8aeded47",
            "input": "Maternal diabetes is a risk factor for pregnancy complications, including stillbirth and macrosomia. Evolving data suggest that diabetes during pregnancy also has long-term consequences for offspring, putting them at risk for obesity and the metabolic syndrome in childhood. Because nonalcoholic fatty liver disease is known to occur in adults and children with insulin resistance, we hypothesized that altered lipid metabolism in fetuses of diabetic mothers may manifest with hepatic steatosis.', 'We undertook a retrospective autopsy study to compare the presence and degree of hepatic steatosis between stillborns delivered to women with pregestational or gestational diabetes mellitus (gestational age 20-40 weeks; n\\u200a=\\u200a33) and age-matched nondiabetic control stillbirth cases (n\\u200a=\\u200a48), the latter enriched for maternal obesity, macrosomia, and similar cause of demise.', 'Histopathologic hepatic steatosis was significantly more prevalent and severe in the diabetic subjects (26/33, 78.8%) than in the controls (8/48, 16.6%) (P\\u200a<\\u200a0.001). Within the diabetic cohort, the severity of steatosis was related directly to gestational age, birth weight, and liver weight, with no correlation of presence or severity of steatosis in the control group to maternal or fetal factors, including maternal body mass index or fetal macrosomia. Although macrosomic stillborns were more common in diabetic women with %hemoglobin A1c >6 and body mass index >30 kg/m, fetal steatosis was independent of glycemic control, maternal obesity, type of diabetes, ethnicity, or fetal sex in our cohort.",
            "output": [
                "Is hepatic steatosis prevalent in stillborns delivered to women with diabetes mellitus?"
            ]
        },
        {
            "id": "task847-150096e3af0b42d593cf9ff103033e57",
            "input": "To examine the effects of lunches with different dietary energy densities on food preferences between genders.', 'Randomized crossover study. Participants were administered the following packed test meals once weekly on a specified day during six sessions: control (150 g of rice with a saut\u00e9ed beef entr\u00e9e containing 40 g of raw beef and 240 g of vegetables), high-meat/low-rice, low-vegetable, medium-fat/low-vegetable, high-fat and high-fat/low-vegetable meals. Subjective levels of sensory properties were assessed over time using visual analogue scales.', 'University of Tokushima Graduate School, Tokushima, Japan.', 'Sixty-five men and sixty-five women matched by age and BMI.', 'Men showed significantly stronger desires for salty and fatty foods after meals (P<0.05). Women showed a significantly stronger desire for sweetness from 2 h after the low-vegetable meal, and increasing fat content under high-vegetable conditions caused a significant stimulated sweetness desire in women more than in men (P<0.05). Moreover, after a high-meat/low-rice meal with 100 g of rice, sweetness desire was stronger in women (P=0.024), whereas no significant differences in sweetness desire were shown between genders after another low-energy-density control meal with 150 g of rice.",
            "output": [
                "Is high-fat diet-related stimulation of sweetness desire greater in women than in men despite high vegetable intake?"
            ]
        },
        {
            "id": "task847-fe61f114d2a24d4dbb9033140f27ce80",
            "input": "Although allergic sensitization can be generated against various allergens, it is unknown how such a diversity of antigens is able to promote TH2-mediated inflammation leading to atopy. Our previous studies demonstrated that allergen-specific IgG immune complexes (ICs) and house dust mite (HDM) extract both induced dendritic cells (DCs) to drive TH2-mediated inflammation, but the mechanism by which these diverse stimuli produce similar responses is unknown.', 'We sought to identify the DC signaling pathways used by TH2 stimuli to promote TH2-mediated inflammation.', 'C57BL/6, Fc\u03b3RIII(-/-), FcR\u03b3(-/-), and ST2(-/-) mice were sensitized and challenged with HDM, and inflammation was assessed based on results of flow cytometry and histology and cytokine production. Bone marrow-derived DCs from these strains were used in signaling and adoptive transfer experiments.', 'Our findings indicate that 2 distinct TH2 stimuli, ICs and HDM, use the FcR\u03b3-associated receptors Fc\u03b3RIII and Dectin-2, respectively, to promote TH2-mediated lung inflammation. In this study we demonstrate that both ICs and HDM induce expression of IL-33, a critical mediator in asthma pathogenesis and the differentiation of TH2 cells, in DCs. Upregulation of IL-33 in DCs is dependent on FcR\u03b3, Toll-like receptor 4, and phosphoinositide 3-kinase. Exogenous IL-33 is sufficient to restore the development of TH2 responses in FcR\u03b3-deficient mice. Finally, adoptive transfer of allergen-pulsed FcR\u03b3(+/-) bone-marrow derived DCs restores the development of TH2-type inflammation in FcR\u03b3-deficient mice, demonstrating the necessity of this signaling pathway in DCs for allergen-induced inflammation.",
            "output": [
                "Does signaling through FcR\u03b3-associated receptors on dendritic cells drive IL-33-dependent TH2-type responses?"
            ]
        },
        {
            "id": "task847-96cef98e13534830806b84ac6f2ef7af",
            "input": "Alzheimer's disease (AD) is characterized by cerebral deposition of \u03b2-amyloid peptide (A\u03b2). A\u03b2 is produced by sequential cleavage of the Amyloid Precursor Protein (APP) by \u03b2- and \u03b3-secretases. Many studies have demonstrated that the internalization of APP from the cell surface can regulate A\u03b2 production, although the exact organelle in which A\u03b2 is produced remains contentious. A number of recent studies suggest that intracellular trafficking also plays a role in regulating A\u03b2 production, but these pathways are relatively under-studied. The goal of this study was to elucidate the intracellular trafficking of APP, and to examine the site of intracellular APP processing.\", 'We have tagged APP on its C-terminal cytoplasmic tail with photoactivatable Green Fluorescent Protein (paGFP). By photoactivating APP-paGFP in the Golgi, using the Golgi marker Galactosyltranferase fused to Cyan Fluorescent Protein (GalT-CFP) as a target, we are able to follow a population of nascent APP molecules from the Golgi to downstream compartments identified with compartment markers tagged with red fluorescent protein (mRFP or mCherry); including rab5 (early endosomes) rab9 (late endosomes) and LAMP1 (lysosomes). Because \u03b3-cleavage of APP releases the cytoplasmic tail of APP including the photoactivated GFP, resulting in loss of fluorescence, we are able to visualize the cleavage of APP in these compartments. Using APP-paGFP, we show that APP is rapidly trafficked from the Golgi apparatus to the lysosome; where it is rapidly cleared. Chloroquine and the highly selective \u03b3-secretase inhibitor, L685, 458, cause the accumulation of APP in lysosomes implying that APP is being cleaved by secretases in the lysosome. The Swedish mutation dramatically increases the rate of lysosomal APP processing, which is also inhibited by chloroquine and L685, 458. By knocking down adaptor protein 3 (AP-3; a heterotetrameric protein complex required for trafficking many proteins to the lysosome) using siRNA, we are able to reduce this lysosomal transport. Blocking lysosomal transport of APP reduces A\u03b2 production by more than a third.",
            "output": [
                "Is the Amyloid Precursor Protein rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid?"
            ]
        },
        {
            "id": "task847-dac4bb90efed44e08c5d3eeffd163ba3",
            "input": "The study aimed to test the hypothesis that therapeutic treatment with a mammalian target of rapamycin complex 1 inhibitor reduces renal cell proliferation and attenuates glomerular and tubulointerstitial injury in the early phase of nephrotoxic serum nephritis (NSN) in rats.', 'Male Wistar-Kyoto rats received a single tail-vein injection of sheep anti-rat glomerular basement membrane serum (day 0) and were treated with vehicle or sirolimus (0.25 mg/kg/day by subcutaneous injection) from day 1 until day 14.', 'Treatment with sirolimus attenuated kidney enlargement by 41% (P<0.05), improved endogenous creatinine clearance by 50% (P<0.05), and reduced glomerular and tubulointerstitial cell proliferation by 53% and 70%, respectively, (P<0.05 compared to vehicle) in rats with NSN. In glomeruli, sirolimus reduced segmental fibrinoid necrosis by 69%, autologous rat immunoglobulin G deposition, glomerular capillary tuft enlargement, and periglomerular myofibroblast (\u03b1-smooth muscle actin-positive cells) accumulation (all P<0.05) but did not significantly affect glomerular crescent formation (P=0.15), macrophage accumulation (P=0.25), or the progression of proteinuria. In contrast, sirolimus preserved tubulointerstitial structure and attenuated all markers of injury (interstitial ED-1- and \u03b1-smooth muscle actin-positive cells and tubular vimentin expression; all P<0.05). By immunohistochemistry and Western blot analysis, sirolimus reduced the glomerular and tubulointerstitial expression of phosphorylated (Ser 235/236) S6-ribosomal protein (P<0.05).",
            "output": [
                "Does induction monotherapy with sirolimus have selected beneficial effects on glomerular and tubulointersititial injury in nephrotoxic serum nephritis?"
            ]
        },
        {
            "id": "task847-fcad60e6a42843ca90e1b44f83426f66",
            "input": "Serrated lesions are an important contributor to colorectal cancer (CRC), notably in the proximal colon. Findings in the distal colorectum are markers of advanced proximal adenomatous neoplasia. However, it is not known whether they affect the odds of advanced proximal serrated lesions.', 'We performed a retrospective cross-sectional study of data from 1910 patients (59.3 \u00b1 8.0 years, 53.8% female) who underwent an average-risk screening colonoscopy from August 2005 through April 2012 at Indiana University Hospital and an associated ambulatory surgery center. Colonoscopies were performed by an endoscopist with high rates of detection of adenomas and serrated polyps. Tissue samples of all serrated polyps (hyperplastic, sessile serrated adenoma/polyp [SSA/P], or traditional serrated adenoma) proximal to the sigmoid colon and serrated polyps >5 mm in the rectum or sigmoid colon were reviewed by a gastrointestinal pathologist and reclassified on the basis of World Health Organization criteria. Advanced serrated lesion (ASL) was defined as SSA/P with cytologic dysplasia, SSA/P \u226510 mm, or traditional serrated adenoma. Advanced conventional adenomatous neoplasia (ACN) was defined as tubular adenoma \u226510 mm, villous histology, high-grade dysplasia, or cancer. The prevalence of proximal ASL and ACN was calculated on the basis of distal colorectal findings. Multivariable logistic regression analysis was performed to determine the age-adjusted and sex-adjusted odds of advanced proximal adenomatous and serrated lesions. Secondary analyses were performed to examine the effect of variable ASL definitions.', 'Fifty-two patients (2.7%) had proximal ASL, and 99 (5.2%) had proximal ACN. Of the 52 patients with proximal ASL, 27 (52%) had no distal polyps. Of the 99 patients with proximal ACN, 40 (40%) had no distal polyps. Age and type of distal adenomas were significantly associated with proximal ACN. There were no significant associations between distal polyp type and proximal ASL. In secondary analyses, distal SSA/Ps (P\\xa0= .008) but not distal hyperplastic polyps or conventional adenomas were associated with any proximal SSA/P.",
            "output": [
                "Are findings in the distal colorectum associated with proximal advanced serrated lesions?"
            ]
        },
        {
            "id": "task847-cbc024a9e55745d08c717f3f1258786a",
            "input": "Bradykinin is a neuropeptide released after tissue damage which plays an important role in inflammatory pain. The up-regulation of the bradykinin B1 receptor in response to inflammation makes it an attractive target for drug development. Aim was to investigate if the selective B1 receptor antagonist BI113823 reduces inflammation-induced mechanical hyperalgesia and if the effect is mediated via peripheral and/or spinal B1 receptor antagonism.', \"Electrophysiological recordings of peripheral afferents and spinal neurons were combined with behavioural experiments to better understand the underlying mechanisms of B1 receptor antagonism. Experiments were performed 24\\u2009h after injection of complete Freund's adjuvant (CFA) or saline into the paw of Wistar rats. A gene expression analysis for the B1 receptor was performed in different tissues. BI113823 was administered orally or intrathecally to assess effects on CFA-induced hyperalgesia. Peripheral afferents of the saphenous nerve as well as spinal wide dynamic range (WDR) and nociceptive-specific (NS) neurons were recorded, and mechanosensitivity was measured before and after BI113823 administration.\", 'BI113823 reduced CFA-induced mechanical hyperalgesia when administered orally or intrathecally. An increased B1 receptor gene expression was found in peripheral and spinal neural tissue. BI113823 significantly reduced mechanosensitivity of peripheral afferents and spinal NS neurons, but had no effect on WDR neurons.",
            "output": [
                "Does the bradykinin B1 receptor antagonist BI113823 reverse inflammatory hyperalgesia by desensitization of peripheral and spinal neurons?"
            ]
        },
        {
            "id": "task847-ffce930a0b154ac6bb0cf37f96c79c67",
            "input": "Recent work has identified deficits in dual-task gait balance control for up to 2 months after adolescent concussion; however, how resumption of preinjury physical activities affects recovery is unknown.', 'The objective of this study is to examine how return to activity (RTA) affects recovery from concussion on measures of symptom severity, cognition, and balance control during single-task and dual-task walking.', 'Nineteen adolescents with concussion who returned to preinjury activity within 2 months after injury and 19 uninjured, matched controls completed symptom inventories, computerized cognitive testing, and single-task and dual-task gait analyses. Concussion participants were assessed at five time points: within 72 h, 1 wk, 2 wk, 1 month, and 2 months postinjury. Control participants were assessed at the same time points as their matched concussion counterparts. RTA day was documented as the postinjury day in which physical activity participation was allowed. The effect of returning to physical activity was assessed by examining the percent change on each dependent variable across time before and directly after the RTA. Data were analyzed by two-way mixed effects ANOVAs.', 'After the RTA day, concussion participants significantly increased their total center-of-mass medial/lateral displacement (P = 0.009, \u03b7p = .175) and peak velocity (P = 0.048, \u03b7p = 0.104) during dual-task walking when compared with pre-RTA data, whereas no changes for the concussion group or between groups were detected on measures of single-task walking, forward movement, or cognition.",
            "output": [
                "Does return to activity after concussion affect dual-task gait balance control recovery?"
            ]
        },
        {
            "id": "task847-8d5a482b189643a98c665a02e345a88f",
            "input": "Clinically, early life stress and anxiety disorders are associated with increased vulnerability for alcohol use disorders. In male rats, early life stress, imparted by adolescent social isolation, results in long-lasting increases in a number of behavioral risk factors for alcoholism, including greater anxiety-like behaviors and ethanol (EtOH) intake. Several recent studies have begun to use this model to gain insight into the relationships among anxiety measures, stress, EtOH intake, and neurobiological correlates driving these behaviors. As prior research has noted significant sex differences in the impact of adolescent stress on anxiety measures and EtOH drinking, the current study was conducted to determine if this same model produces an \"addiction vulnerable\" phenotype in female rodents.', 'Female Long Evans rats were socially isolated (SI; 1/cage) or group housed (GH; 4/cage) for 6\\xa0weeks during adolescence. After this housing manipulation, behavioral assessment was conducted using the elevated plus maze, response to novelty in an open field environment, and the light/dark box. After behavioral testing, home cage EtOH drinking was assessed across an 8-week period.', 'No group differences were detected in any of the behavioral measures of unconditioned anxiety-like behavior. Greater EtOH intake and preference were observed in SI females but these differences did not persist.",
            "output": [
                "Does adolescent social isolation lead to persistent increases in anxiety- like behavior or ethanol intake in female long-evans rats?"
            ]
        },
        {
            "id": "task847-b17518851a1645d2a151dbc53549781e",
            "input": "Previous studies have suggested that DNA methylation contributes to coronary artery disease (CAD) risk variability. DNA hypermethylation at the ATP-binding cassette transporter A1 (ABCA1) gene, an important modulator of high-density lipoprotein cholesterol and reverse cholesterol transport, has been previously associated with plasma lipid levels, aging and CAD, but the association with CAD has yet to be replicated.', 'ABCA1 DNA methylation levels were measured in leucocytes of 88 men using bis-pyrosequencing. We first showed that DNA methylation at the ABCA1 gene promoter locus is associated with aging and CAD occurrence in men (P\\u2009<\\u20090.05). The latter association is stronger among older men with CAD (\u226561\\xa0years old; n\\u2009=\\u200919), who showed at least 4.7% higher ABCA1 DNA methylation levels as compared to younger men with CAD (<61\\xa0years old; n\\u2009=\\u200919) or men without CAD (n\\u2009=\\u200950; P\\u2009<\\u20090.001). Higher ABCA1 DNA methylation levels in older men were also associated with higher total cholesterol (r\\u2009=\\u20090.34, P\\u2009=\\u20090.03), low-density lipoprotein cholesterol (r\\u2009=\\u20090.32, P\\u2009=\\u20090.04) and triglyceride levels (r\\u2009=\\u20090.26, P\\u2009=\\u20090.09). Furthermore, we showed that acetylsalicylic acid therapy is associated with 3.6% lower ABCA1 DNA methylation levels (P\\u2009=\\u20090.006), independent of aging and CAD status of patients.",
            "output": [
                "Are acetylsalicylic acid , aging and coronary artery disease associated with ABCA1 DNA methylation in men?"
            ]
        },
        {
            "id": "task847-ef378624666a4ce4b4e125508c09ea59",
            "input": "In advanced cancer, including glioblastoma, the TGF\u03b2 pathway acts as an oncogenic factor. Some tumors exhibit aberrantly high TGF\u03b2 activity, and the mechanisms underlying this phenomenon are not well understood. We have observed that TGF\u03b2 can induce TGF\u03b22, generating an autocrine loop leading to aberrantly high levels of TGF\u03b22. We identified cAMP-responsive element-binding protein 1 (CREB1) as the critical mediator of the induction of TGF\u03b22 by TGF\u03b2. CREB1 binds to the TGFB2 gene promoter in cooperation with SMAD3 and is required for TGF\u03b2 to activate transcription. Moreover, the PI3K-AKT and RSK pathways regulate the TGF\u03b22 autocrine loop through CREB1. The levels of CREB1 and active phosphorylated CREB1 correlate with TGF\u03b22 in glioblastoma. In addition, using patient-derived in vivo models of glioblastoma, we found that CREB1 levels determine the expression of TGF\u03b22. Our results show that CREB1 can be considered a biomarker to stratify patients for anti-TGF\u03b2 treatments and a therapeutic target in glioblastoma.",
            "output": [
                "Does active CREB1 promote a malignant TGF\u03b22 autocrine loop in glioblastoma?"
            ]
        },
        {
            "id": "task847-9bdf13529dbc44ae87a9e703ad014a27",
            "input": "Are submaximal and maximal exercise tests reliable, valid and acceptable in people with chronic pain, fibromyalgia and fatigue disorders?', 'Systematic review of studies of the psychometric properties of exercise tests.', 'People older than 18 years with chronic pain, fibromyalgia and chronic fatigue disorders.', 'Studies of the measurement properties of tests of physical capacity in people with chronic pain, fibromyalgia or chronic fatigue disorders were included.', \"Studies were required to report: reliability coefficients (intraclass correlation coefficient, alpha reliability coefficient, limits of agreements and Bland-Altman plots); validity coefficients (intraclass correlation coefficient, Spearman's correlation, Kendal T coefficient, Pearson's correlation); or dropout rates.\", 'Fourteen studies were eligible: none had low risk of bias, 10 had unclear risk of bias and four had high risk of bias. The included studies evaluated: \u00c5strand test; modified \u00c5strand test; Lean body mass-based \u00c5strand test; submaximal bicycle ergometer test following another protocol other than \u00c5strand test; 2-km walk test; 5-minute, 6-minute and 10-minute walk tests; shuttle walk test; and modified symptom-limited Bruce treadmill test. None of the studies assessed maximal exercise tests. Where they had been tested, reliability and validity were generally high. Dropout rates were generally acceptable. The 2-km walk test was not recommended in fibromyalgia.",
            "output": [
                "Are several submaximal exercise tests reliable , valid and acceptable in people with chronic pain , fibromyalgia or chronic fatigue : a systematic review?"
            ]
        },
        {
            "id": "task847-de4e031f907045909a820c4da862506b",
            "input": "Anorectal manometry provides objective information about anorectal function, but its results depend on the examiner's skill, the type of equipment, and subject characteristics like age or gender. This single institution, prospective study was performed to investigate the effect of gender and age on the results of anorectal manometry.\", 'All included subjects completed a questionnaire to assess their bowel function. The survey included 13 validated questions (eight on constipation and five on incontinence) and was used to exclude subjects with pathological constipation or incontinence. Subjects with normal bowel function underwent anorectal manometry to measure anal sphincter length (ASL), maximum resting pressure (MRP), and maximum squeeze pressure (MSP), and the results were compared by gender and age.', 'The mean age of the 154 participants (94 male and 60 female) was 59.1 years. ASL was greater in men (4.23 vs. 3.85 cm, p\\u2009<\\u20090.001). MRP was not significantly different according to gender (p\\u2009=\\u20090.93), but MSP was higher in men (190.18 vs. 116.49 mmHg, p\\u2009<\\u20090.001). ASL did not correlate with age (p\\u2009=\\u20090.707). MRP was inversely related to age in both men (R (2)\\u2009=\\u20090.152, p\\u2009<\\u20090.001) and women (R (2)\\u2009=\\u20090.282, p\\u2009<\\u20090.001), and MSP only in women (R (2)\\u2009=\\u20090.210, p\\u2009<\\u20090.001).",
            "output": [
                "Are anorectal manometric parameters influenced by gender and age in subjects with normal bowel function?"
            ]
        },
        {
            "id": "task847-9fa6c861420f4845afa83fd210ded6de",
            "input": "In breast cancer, distinct expression profiles of microRNAs (miRNAs) have been associated with molecular subgroups and clinicopathological characteristics, implicating a diagnostic and prognostic role of miRNAs. However, the biological functions of deregulated miRNAs in tumor progression are not yet completely defined. In this study, we investigated the function of miR-18a in regulating breast cancer metastasis through the hypoxia-inducible factor 1\u03b1 (HIF1A)-dependent hypoxic response.', \"An orthotopic metastatic breast cancer xenograft model (MDA-MB-231 cells) was used to identify miRNAs associated with spontaneous lung metastasis. The function of miR-18a in regulating HIF1A expression, as well as cellular responses to hypoxia and metastasis, were then studied in vitro and in vivo by assessing ectopic miR-18a expression or miR-18a inhibition. miRNA-mRNA interactions (AGO2 immunoprecipitation and 3' untranslated region Luciferase reporter assays), gene expression (quantitative PCR and microarray), cell migration and invasion, and cell growth were assessed under normoxic or hypoxic conditions, complemented by orthotopic xenograft of tumor cells to the mammary fat pad to investigate the effect of modulating miR-18a expression on primary tumor growth and lung metastasis. Last, clinically relevant correlations between miR-18a, HIF1A, hypoxia-responsive gene expression and distant metastasis-free survival (DMFS) were assessed using published expression array breast tumors data sets.\", 'miRNAs encoded by the MIR17HG gene were downregulated in lung metastases compared to primary tumors. Ectopic expression of miR-18a, a MIR17HG family member, in a metastatic variant of MDA-MB-231 cells reduced primary tumor growth and lung metastasis, whereas miR-18a inhibition in the parental cells promoted tumor growth and lung metastasis. We identified HIF1A as a direct target of miR-18a. Modulating miR-18a expression significantly affected hypoxic gene expression, cell invasiveness and sensitivity to anoikis and hypoxia in vitro in a HIF1A-dependent manner. Analysis of previously published data revealed that higher expression of HIF1A and a panel of hypoxic genes is associated with shorter DMFS interval in patients with basal-like breast tumors, and that, within this subtype, miR-18a expression is inversely correlated with hypoxic gene expression. Together, these data support a role of miR-18a in repressing distant metastasis through a HIF1A-dependent pathway.",
            "output": [
                "Does microRNA-18a inhibit hypoxia-inducible factor 1\u03b1 activity and lung metastasis in basal breast cancers?"
            ]
        },
        {
            "id": "task847-ce18ff46ca1b4c7fa43485470ec9fc43",
            "input": "Embryo transfer to a developed endometrium is an important prognostic factor in frozen-thawed embryo transfer cycle outcome. Vaginal estrogen, such as Vagifem vaginal tablets and Premarin vaginal cream, is a regimen used for the patients with refractive endometria.', 'Our objective was to compare the effects of Vagifem and Premarin on the endometrial thickness of the patients with refractive endometria.', 'In this randomized clinical trial, 30 patients with refractive endometria in frozen-thawed embryo transfer cycles received Vagifem vaginal tablets and 30 women received Premarin vaginal cream. Endometrial thickness was measured on the 14th day of drug administration.', 'Comparing the endometrial thicknesses of the two groups showed that the endometria of the Vagifem group was significantly thicker than that of the Premarin group (5.93\u00b10.38 vs. 6.74\u00b10.32; p<0.001).",
            "output": [
                "Is vagifem superior to vaginal Premarin in induction of endometrial thickness in the frozen-thawed cycle patients with refractory endometria : A randomized clinical trial?"
            ]
        },
        {
            "id": "task847-d5dfe76fb877471fbb735e9f6d008d6e",
            "input": "SUMO-specific protease 1 (SENP1) removes SUMO from proteins and plays important roles in the regulation of multiple cellular signalling pathways. However, little is known about the role of SENP1 in coronary heart disease. In this study, we tested the hypothesis that SENP1 protects against myocardial ischaemia/reperfusion (I/R) injury and investigated the underlying molecular mechanisms involved.', 'First, we found that SENP1 levels increased after I/R in human and mouse myocardium in vivo and in rat cardiomyocytes in vitro. We then performed coronary artery ligation to induce I/R injury in wild-type (WT) and heterozygous SENP1-knockdown (SENP1(+/-)) mice. Compared with WT mice, SENP1(+/-) mice had normal cardiac function at baseline but lower systolic function after I/R. Post-I/R myocardial infarction sizes were larger in SENP1(+/-) mice. Furthermore, we demonstrated that SENP1 regulates the expression of hypoxia-inducible factor 1 \u03b1 (HIF1\u03b1), a critical protective factor during I/R, in vivo and in vitro. Overexpression of HIF1\u03b1 reversed the deteriorating effect of SENP1 knockdown on cellular death.",
            "output": [
                "Does sENP1 protect against myocardial ischaemia/reperfusion injury via a HIF1\u03b1-dependent pathway?"
            ]
        },
        {
            "id": "task847-9631d24701864d25838cd2e643b9bbb7",
            "input": "From our previous clinical trials, intracoronary infusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells ((mob)PBMCs) proved to be effective in improving myocardial contractility and reducing infarct volume in acute myocardial infarction. We tested the effect of priming (mob)PBMCs with erythropoietin (EPO) to augment its therapeutic efficacy.', '(mob)PBMCs were obtained from healthy volunteers after a 3-day subcutaneous injection of G-CSF (10 \u03bcg/kg). About 40% of (mob)PBMCs were EPO receptor (EPOR) (+) and responded to 6 h EPO-priming (10 IU/mL) by increasing the expression of vasculogenic factors (i.e. IL8, IL10, bFGF, PDGF, MMP9) and adhesion molecules (i.e. integrin \u03b1V, \u03b21, \u03b22, \u03b28) through the JAK2 and Akt pathway. These responses were also observed in PBMCs from elderly patients with coronary disease. The conditioned media from EPO-primed (mob)PBMCs contained various cytokines such as IL8, IL10, TNF\u03b1, and PDGF, which enhanced the migration and tube formation capability of endothelial cells. EPO-primed (mob)PBMCs also showed increased adhesion on endothelial cells or fibronectin. Augmented vasculogenic potential of EPO-primed (mob)PBMCs was confirmed in a Matrigel plug assay, ischaemic hindlimb, and myocardial infarction models of athymic nude mice. There were two action mechanisms: (i) cellular effects confirmed by direct incorporation of human (mob)PBSCs into mouse vasculature and (ii) indirect humoral effects confirmed by the therapeutic effect of the supernatant of EPO-primed (mob)PBMCs.",
            "output": [
                "Does erythropoietin priming improve the vasculogenic potential of G-CSF mobilized human peripheral blood mononuclear cells?"
            ]
        },
        {
            "id": "task847-2c728f80118444e2b5c3c1c9b0363688",
            "input": "We investigated whether glucose fluctuations aggravate cardiac fibrosis and increase the occurrence of atrial fibrillation (AF) in rats with diabetes mellitus (DM).', 'Streptozotocin-induced diabetic rats were randomly divided into three groups: uncontrolled DM (U-STZ) group, controlled DM (C-STZ) group, and DM with glucose fluctuations (STZ-GF) group. Glucose fluctuations were induced by fasting for 24 h and additional regular insulin injections (0.5 IU/kg) administered three times per week for three consecutive weeks. C-STZ rats were administered long acting insulin (20 IU/kg) twice a day to control blood glucose levels. Cardiac fibrosis evaluated by Masson trichrome staining and the expressions of collagen type 1, collagen type 3, and \u03b1-smooth muscle actin were increased in U-STZ rats compared with C-STZ rats, which were more pronounced in STZ-GF rats. The inducibility of AF was significantly larger in U-STZ rats than C-STZ rats and was greatest in STZ-GF rats. To explore the mechanism of cardiac fibrosis, we investigated the levels of reactive oxygen species (ROS) and apoptosis. The expression of malondialdehyde, an indicator of ROS levels, was significantly upregulated in STZ-GF rats compared with U-STZ rats, along with increased thioredoxin-interacting protein (Txnip) expression in STZ-GF rats. Furthermore, caspase-3 expression and the number of TUNEL-positive cells were significantly increased in STZ-GF rats compared with U-STZ and C-STZ rats.",
            "output": [
                "Do glucose fluctuations increase the incidence of atrial fibrillation in diabetic rats?"
            ]
        },
        {
            "id": "task847-4b22dcfa05d1457a8593222dc58b6d0e",
            "input": "Physical activity and sedentary behavior measurement tools need to be validated in free-living settings. Direct observation (DO) may be an appropriate criterion for these studies. However, it is not known if trained observers can correctly judge the absolute intensity of free-living activities.', 'To compare DO estimates of total MET-hours and time in activity intensity categories to a criterion measure from indirect calorimetry (IC).', 'Fifteen participants were directly observed on three separate days for two hours each day. During this time participants wore an Oxycon Mobile indirect calorimeter and performed any activity of their choice within the reception area of the wireless metabolic equipment. Participants were provided with a desk for sedentary activities (writing, reading, computer use) and had access to exercise equipment (treadmill, bike).', 'DO accurately and precisely estimated MET-hours [% bias (95% CI) = -12.7% (-16.4, -7.3), ICC = 0.98], time in low intensity activity [% bias (95% CI) = 2.1% (1.1, 3.2), ICC = 1.00] and time in moderate to vigorous intensity activity [% bias (95% CI) -4.9% (-7.4, -2.5), ICC = 1.00].",
            "output": [
                "Is direct observation a valid criterion for estimating physical activity and sedentary behavior?"
            ]
        },
        {
            "id": "task847-2c9c494dc1c54d4094bcfa1760ec5732",
            "input": "Increased expression of nitric oxide synthase (NOS) and an increase in plasma nitrite plus nitrate (NOx) have been reported in patients with pulmonary fibrosis, suggesting that nitric oxide (NO) plays an important role in its development. However, the roles of the entire NO and NOS system in the pathogenesis of pulmonary fibrosis still remain to be fully elucidated. The aim of the present study is to clarify the roles of NO and the NOS system in pulmonary fibrosis by using the mice lacking all three NOS isoforms.', 'Wild-type, single NOS knockout and triple NOS knockout (n/i/eNOS-/-) mice were administered bleomycin (BLM) intraperitoneally at a dose of 8.0\\xa0mg/kg/day for 10 consecutive days. Two weeks after the end of the procedure, the fibrotic and inflammatory changes of the lung were evaluated. In addition, we evaluated the effects of long-term treatment with isosorbide dinitrate, a NO donor, on the n/i/eNOS-/- mice with BLM-induced pulmonary fibrosis.', 'The histopathological findings, collagen content and the total cell number in bronchoalveolar lavage fluid were the most severe/highest in the n/i/eNOS-/- mice. Long-term treatment with the supplemental NO donor in n/i/eNOS-/- mice significantly prevented the progression of the histopathological findings and the increase of the collagen content in the lungs.",
            "output": [
                "Does nitric oxide exert protective effects against bleomycin-induced pulmonary fibrosis in mice?"
            ]
        },
        {
            "id": "task847-98a8e7632f92466b840fdc74f21d9bda",
            "input": "Inhaled corticosteroids are anti-inflammatory medications that can down-regulate the immunologic response in patients with COPD; however, their role at onset of COPD exacerbation is still not understood. The aim of this study was to assess the early inflammatory response and clinical presentation of patients with COPD exacerbation mediated by inhaled corticosteroids.', 'Prospective data were collected on 123 hospitalized subjects with COPD exacerbation over a 30-month period at 2 Spanish university hospitals. Based on domiciliary use, comparative analyses were performed between subjects who did not use inhaled corticosteroids (n = 58) and subjects who did (n = 65). Measurements of serum biomarkers were recorded on admission to the hospital (day 1) and on day 3; clinical, physiological, microbiological, and severity data and mortality/readmission rates were also recorded.', 'At days 1 and 3, both groups showed a similar inflammatory response; fluticasone produced lower levels of interleukin-8 compared with budesonide (P < .01). All clinical features considered were similar in the 2 groups; multivariate analysis predicting clinical complications on hospitalization showed air-flow obstruction severity as the only predictive factor (odds ratio 3.13, 95% CI 1.13-8.63, P = .02).",
            "output": [
                "Do inhaled corticosteroids influence the early inflammatory response and clinical presentation of hospitalized subjects with COPD exacerbation?"
            ]
        },
        {
            "id": "task847-0cefe1ceffbd4cfeb7ac08f4bfb13541",
            "input": "Damaged, necrotic, or apoptotic hepatocytes release damage-associated molecular patterns that initiate sterile inflammation, and liver inflammation drives liver injury and fibrosis. Here we identified hepatic nuclear factor kappa B (NF-\u03baB)-inducing kinase (NIK), a Ser/Thr kinase, as a novel trigger of fatal liver inflammation. NIK is activated by a broad spectrum of stimuli. It was up-regulated in injured livers in both mice and humans. In primary mouse hepatocytes, NIK overexpression stimulated, independently of cell injury and death, release of numerous chemokines and cytokines that activated bone marrow-derived macrophages (BMDMs). BMDMs in turn secreted proapoptotic molecules that stimulated hepatocyte apoptosis. Hepatocyte-specific expression of the NIK transgene triggered massive liver inflammation, oxidative stress, hepatocyte apoptosis, and liver fibrosis, leading to weight loss, hypoglycemia, and death. Depletion of Kupffer cells/macrophages reversed NIK-induced liver destruction and death.",
            "output": [
                "Does mouse hepatocyte overexpression of NF-\u03baB-inducing kinase ( NIK ) trigger fatal macrophage-dependent liver injury and fibrosis?"
            ]
        },
        {
            "id": "task847-29e6a8305e7f412681780e9726232c6b",
            "input": "Members of the Ewing sarcoma family of tumors (ESFT) contain tumor-associated translocations that give rise to oncogenic transcription factors, most commonly EWS/FLI1. EWS/FLI1 plays a dominant role in tumor progression by modulating the expression of hundreds of target genes. Here, the impact of EWS/FLI1 inhibition, by RNAi-mediated knockdown, on cellular signaling was investigated using mass spectrometry-based phosphoproteomics to quantify global changes in phosphorylation. This unbiased approach identified hundreds of unique phosphopeptides enriched in processes such as regulation of cell cycle and cytoskeleton organization. In particular, phosphotyrosine profiling revealed a large upregulation of STAT3 phosphorylation upon EWS/FLI1 knockdown. However, single-cell analysis demonstrated that this was not a cell-autonomous effect of EWS/FLI1 deficiency, but rather a signaling effect occurring in cells in which knockdown does not occur. Conditioned media from knockdown cells were sufficient to induce STAT3 phosphorylation in control cells, verifying the presence of a soluble factor that can activate STAT3. Cytokine analysis and ligand/receptor inhibition experiments determined that this activation occurred, in part, through an IL6-dependent mechanism. Taken together, the data support a model in which EWS/FLI1 deficiency results in the secretion of soluble factors, such as IL6, which activate STAT signaling in bystander cells that maintain EWS/FLI1 expression. Furthermore, these soluble factors were shown to protect against apoptosis.",
            "output": [
                "Does phosphoproteomic profiling reveal IL6-mediated paracrine signaling within the Ewing sarcoma family of tumors?"
            ]
        },
        {
            "id": "task847-ecde9154e1a24b55a29046648d32bbb4",
            "input": "Onset of sexual activity during adolescence is common in Vanuatu, however access to comprehensive sexual and reproductive health (SRH) information is limited. Improving adolescents' knowledge about SRH is necessary to improve health outcomes, however little is known about the information needs and preferences of adolescents in the Pacific to inform policy and programs in this region.\", 'Sixty-six focus group discussions were conducted with 341 male and female adolescents aged 15-19 years from rural and urban communities on two islands of Vanuatu. Twelve key-informant interviews were also conducted with policymakers and health service providers. Data were analysed thematically using an inductive approach.', \"Much of the SRH information targeting adolescents focused on sexually transmitted infections and HIV. While this information was valued, important gaps were identified including prevention of pregnancy, condom use, puberty, sexuality and relationships. Peer educators and health workers were adolescents' preferred sources of information because they were considered knowledgeable and trustworthy. Parents were not a common source but were preferred, particularly by girls, despite considerable socio-cultural barriers. Schools were an important but underutilised source of information, as were a range of media sources.",
            "output": [
                "Are `` These issues n't talked about at home '' : a qualitative study of the sexual and reproductive health information preferences of adolescents in Vanuatu?"
            ]
        },
        {
            "id": "task847-5216cd34737e4011992509432ba08bdf",
            "input": "In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass.', 'Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competitive ELISA assay for measurement in serum. Rat tissue extractions in the presence or absence of a series of proteases of interest were used to identify its enzymatic origin. A rat model of dexamethasone (DEX) induced muscle atrophy and a human 56-day bed rest study with and without vibration therapy were used to assess biological and clinical relevance.', 'A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (\u00b13.7) % after 1day of bed rest, and then gradually increased ending up at a 16.4 (\u00b14.6) % increase at day 47.",
            "output": [
                "Does measurement of a MMP-2 degraded Titin fragment in serum reflect changes in muscle turnover induced by atrophy?"
            ]
        },
        {
            "id": "task847-12233fb74bba4d94b8222acdfee0060c",
            "input": "It has been proposed that hepatitis B virus (HBV) sub-genotype A1 infections have mild outcomes and a low risk of drug-resistance among patients infected with human immunodeficiency virus (HIV) receiving lamivudine-containing antiretroviral therapy (ART) without tenofovir in Africa.', 'The virologic expression of HBV sub-genotype A1 coinfection was studied over 12 months in HIV-positive adults starting stavudine/lamivudine/nevirapine in Malawi, using Sanger, deep, clonal, and single full-genome sequencing for the sensitive characterization of HBV resistance-associated mutations (RAMs).', 'Among 1117 subjects, 133 (12%) tested HBsAg-positive. After starting ART, retention rates were 96/133 (72%) at 6 months and 54/133 (41%) at 12 months. Based upon the last available follow-up, 92/96 (96%) subjects achieved HIV-1 RNA <40 copies/mL, 48/96 (50%) showed HBV DNA <14 IU/mL, and 24/96 (25%) acquired HBV RAMs. At 6 months, M204I was detected in 8/46 (17%) and 16/17 (94%) subjects using Sanger and deep sequencing, respectively. At 12 months, all viremic patients had multiple resistance and compensatory mutations coexisting on the same HBV genomes. Comparing HBeA-positive (67/133, 50%) with HBeAg-negative subjects, 64/67 (96%) vs 35/66 (55%) showed baseline HBV DNA >2000 IU/mL (P = .0006), 39/47 (17%) vs 9/49 (82%) had persistent HBV DNA detection during follow-up (P < .0001), and 23/47 (49%) vs 2/49 (4%) acquired HBV RAMs (P < .0001). Baseline HBV DNA levels were median 8.1 vs 5.3 log10 IU/mL in subjects with vs those without treatment-emergent RAMs (P < .0001).",
            "output": [
                "Is hepatitis B virus sub-genotype A1 infection characterized by high replication levels and rapid emergence of drug resistance in HIV-positive adults receiving first-line antiretroviral therapy in Malawi?"
            ]
        },
        {
            "id": "task847-58d435cf7924408da8c8f54d15a02e70",
            "input": "As next-generation sequencing (NGS) becomes a major sequencing platform in clinical diagnostic laboratories, it is critical to identify artifacts that constitute baseline noise and may interfere with detection of low-level gene mutations. This is especially critical for applications requiring ultrasensitive detection, such as molecular relapse of solid tumors and early detection of cancer. We recently observed a ~10-fold higher frequency of C:G\\xa0>\\xa0T:A mutations than the background noise level in both wild-type peripheral blood and formalin-fixed paraffin-embedded samples. We hypothesized that these might represent cytosine deamination events, which have been seen using other platforms.', 'To test this hypothesis, we pretreated samples with uracil N-glycosylase (UNG). Additionally, to test whether some of the cytosine deamination might be a laboratory artifact, we simulated the heat associated with polymerase chain reaction thermocycling by subjecting samples to thermocycling in the absence of polymerase. To test the safety of universal UNG pretreatment, we tested known positive samples treated with UNG.', 'UNG pretreatment significantly reduced the frequencies of these mutations, consistent with a biologic source of cytosine deamination. The simulated thermocycling-heated samples demonstrated significantly increased frequencies of C:G\\xa0>\\xa0T:A mutations without other baseline base substitutions being affected. Samples with known mutations demonstrated no decrease in our ability to detect these after treatment with UNG.",
            "output": [
                "Is cytosine deamination a major cause of baseline noise in next-generation sequencing?"
            ]
        },
        {
            "id": "task847-336758a7647446899bb27982707de338",
            "input": "The pH at the surface of healthy human skin is around 5. Cleansing the skin with soap increases the pH of the skin, which then returns to a more acidic pH within a few hours. However, the effects of skin cleansing with soap over a long time on the pH regulatory system is still unclear.', 'We compared the pH of the skin between users of a soap-based cleanser and of a mild-acidic cleanser prior to and following the cleansing.', 'This study had two groups of subjects, one group who had used a soap-based cleanser for more than 5 years and the other group who had used a mild-acidic cleanser for more than 5 years. The pH on the inner forearm of each subject was measured prior to and for 6 h after cleansing with a soap bar.', 'There were no differences between the pH of the skin these two groups prior to cleansing, immediately after cleansing or in the pH recovery rate for 6 h.",
            "output": [
                "Does the long-term use of soap affect the pH-maintenance mechanism of human skin?"
            ]
        },
        {
            "id": "task847-fc7ae073c4914e1bb104dea4459942c9",
            "input": "In the present study, we investigated the potential effect of aliskiren on smooth muscle cell (SMC) migration in response to prorenin.', \"Cultured human SMCs were incubated with angiotensinogen (ANG) (1.5 \u00d7 10(-7)M) and increasing concentrations of aliskiren (10(-6)-10(-5)M). After 24 h, SMC migration was assessed by Boyden's chamber chemotactic assay using prorenin as chemotactic factor (10(-8)M). The effect of aliskiren on RhoA and Rac activity was also determined by G-LISA assay and the lamellipodia formation by rhodamine-phalloidin staining. Changes in cell morphology were recorded in real-time using the iCelligence system.\", 'Aliskiren determined, at 10(-5)M, a significant inhibition of SMC migration induced by prorenin (-66.4 \u00b1 18.1%; p < 0.05), while no significant effect was observed when PDGF-BB was utilized as chemotactic agent. Aliskiren also reduced Rac-GTP levels in response to prorenin (-54.2 \u00b1 5.4%) without affecting the RhoA-GTP levels. Finally, aliskiren inhibited both the lamellipodia formation and morphological changes induced by prorenin with no significant effect on PDGF-BB activity.",
            "output": [
                "Does aliskiren inhibit prorenin-induced human aortic smooth muscle cell migration?"
            ]
        },
        {
            "id": "task847-41acfac6e67543978a4ba5d4ed31d70d",
            "input": "Our objective was to describe the association between voriconazole concentrations and CYP2C19 diplotypes in pediatric cancer patients, including children homozygous for the CYP2C19*17 gain-of-function allele.', 'A linear mixed effect model compared voriconazole dose-corrected trough concentrations (n = 142) among CYP2C19 diplotypes in 33 patients (aged 1-19 years). Voriconazole pharmacokinetics was described by a two-compartment model with Michaelis-Menten elimination.', 'Age (p = 0.05) and CYP2C19 diplotype (p = 0.002) were associated with voriconazole concentrations. CYP2C19*17 homozygotes never attained therapeutic concentrations, and had lower dose-corrected voriconazole concentrations (median 0.01 \u03bcg/ml/mg/kg; p = 0.02) than CYP2C19*1 homozygotes (median 0.07 \u03bcg/ml/mg/kg). Modeling indicates that higher doses may produce therapeutic concentrations in younger children and in those with a CYP2C19*17/*17 diplotype.",
            "output": [
                "Do voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes?"
            ]
        },
        {
            "id": "task847-ed487b990ce14b2c96f637efff0115b7",
            "input": "This study investigated whether cholesterol levels influence the expression and function of drug transporters and whether statin treatments could alter this by reducing plasma low-density lipoprotein cholesterol levels.', 'The mRNA expression and function of OATP1B1, ABCB1 and ABCG2 were assessed in peripheral blood mononuclear cells (PBMCs) of healthy subjects and from patients with familial hypercholesterolemia (FH) before and after statin treatment by real-time PCR and flow cytometric assay, respectively. The effects of statin exposure and cholesterol depletion in PBMCs and in cell lines were assessed.', 'ABCG2 expression and activity in PBMCs in patients with FH were 2-fold and 26-fold higher, respectively, than those of the healthy subjects (p < 0.001 for both). Statin treatment decreased ABCG2 expression and function in patients with FH. Depletion of cholesterol ex vivo reduced ABCG2 expression in PBMCs and reduced ABCG2 activity in liver and colon cells.",
            "output": [
                "Are expression and activity of ABCG2 , but not ABCB1 or OATP1B1 , associated with cholesterol levels : evidence from in vitro and in vivo experiments?"
            ]
        },
        {
            "id": "task847-f86193051ef7412e88a8c062288ced33",
            "input": "Do teenage girls with a history of menstrual irregularity and/or elevated androgen levels in adolescence exhibit an increased risk of polycystic ovary syndrome (PCOS) and/or infertility later on in adulthood?",
            "output": [
                "Are irregular menstruation and hyperandrogenaemia in adolescence associated with polycystic ovary syndrome and infertility in later life : Northern Finland Birth Cohort 1986 study?"
            ]
        },
        {
            "id": "task847-e403934c2a094931b154964891c26fd4",
            "input": "The current standard of care for glioblastoma (GBM) involves a combination of surgery, radiotherapy, and temozolomide chemotherapy, but this regimen fails to achieve long-term tumor control. Resistance to temozolomide is largely mediated by expression of the DNA repair enzyme MGMT; however, emerging evidence suggests that inactivation of MSH6 and other mismatch repair proteins plays an important role in temozolomide resistance. Here, we investigate endogenous MSH6 mutations in GBM, anaplastic oligodendroglial tumor tissue, and corresponding brain tumor-initiating cell lines (BTIC).', 'MSH6 sequence and MGMT promoter methylation were determined in human tumor samples and BTICs. Sensitivity to temozolomide was evaluated in vitro using BTICs in the absence and presence of O(6)-benzylguanine to deplete MGMT. The influence of MGMT and MSH6 status on in vivo sensitivity to temozolomide was evaluated using intracranial BTIC xenografts.', 'We identified 11 previously unreported mutations in MSH6 in nine different glioma samples and six paired BTIC lines from adult patients. In addition, MSH6 mutations were documented in three oligodendrogliomas and two treatment-na\u00efve gliomas, both previously unreported findings. These mutations were found to influence the sensitivity of BTICs to temozolomide both in vitro and in vivo, independent of MGMT promoter methylation status.",
            "output": [
                "Do novel MSH6 mutations in treatment-na\u00efve glioblastoma and anaplastic oligodendroglioma contribute to temozolomide resistance independently of MGMT promoter methylation?"
            ]
        },
        {
            "id": "task847-4d32f17bc576472a9e80b52949a2f238",
            "input": "The association between blood types and ovarian reserve is investigated in this study.', \"As an index of ovarian reserve, women with a follicle stimulat- ing hormone (FSH) level of \u226510 mIU/ml in the early follicular phase were designated as having diminished ovarian reserve. In this prospective study, early follicular phase serum FSH and estradiol levels and blood types were evaluated in 500 patients who were admitted to the Infertility Department of Ministry of Health Etlik Z\u00fcbeyde Han\u0131m Women's Health Training and Research Hospital between January 2012 and June 2012. Women with serum FSH level <10 mIU/ml formed group I, and women with serum FSH \u226510 mIU/ml formed group II. The prevalence of blood types in each group and their associa- tion with ovarian reserve were analyzed.\", 'Out of 500 patients, 438 women were in group I, while 62 women were in group II. There was no statistically significant difference among the two groups in terms of blood group proportions (p=0.69), this did not change after age adjustment (p=0.77). The presence of A antigen (in A and AB blood type) (p=0.91), the blood type O (p=0.70), and the blood type B (p=0.51) were not statistically related to ovarian reserve after age adjustment. There was also no statistically significant correlation between rhesus factor and ovarian reserve after age adjustment (p=0.83). The only factor that affected ovarian reserve was age of patients (p=0.006).",
            "output": [
                "Is only female age , and not blood type , associated with ovarian reserve?"
            ]
        },
        {
            "id": "task847-b1149039fe9b45169dfbaf8aff77744a",
            "input": "Type 1 endometrial cancer (EC) is typically sex hormone sensitive; however, most women diagnosed with EC have already gone through menopause. Several studies have reported that the postmenopausal ovary is hormonally active, and estradiol (E2) production from the ovaries persists for as much as 10 years beyond menopause. The aim of this study was to evaluate whether sex steroid production from the ovaries contributes to the pathogenesis of type 1 EC.', 'This was a prospective study of 53 women treated for EC (28 cases of type 1 disease and 25 cases of type 2 disease). Serum specimens were collected from the peripheral and ovarian veins of participants undergoing bilateral oophorectomy. The sex steroid hormone levels and hormonal milieu on cervical cytology were evaluated as maturation value (MV). In addition, the degree of stromal hyperplasia of the ovary was evaluated histologically.', 'Although the E2 levels of the peripheral veins did not show any significant differences [8.2 (5.1-12.4) vs 7.4 (5.1-11.7) pg/mL, respectively; P < 0.05], the patients with type 1 EC had a higher E2 level in the ovarian vein than those with type 2 EC [25 (13.8-42.5) vs 15 (10.0-23.0) pg/mL, respectively; P < 0.05]. There were also no significant differences in the rate of moderate to marked hyperplasia of the ovarian stroma between the groups; however, the thickness of the ovarian cortex demonstrated a correlation with the ovarian E2 level. In addition, the MV displayed a strong correlation with the ovarian E2 level, but not the peripheral E2 level.",
            "output": [
                "Do postmenopausal patients with endometrial cancer of type 1 have elevated serum estradiol levels in the ovarian vein?"
            ]
        },
        {
            "id": "task847-237a74d5ed13416bb5f13bf2ddd3c339",
            "input": "Penehyclidine hydrochloride (PHC) is a new anticholinergic drug, which has been shown to have a good curative effect for sepsis. Beta arrestins have been demonstrated to play important roles in sepsis. This study is to investigate the effects of PHC on pulmonary microvascular permeability and on expressions of beta arrestins in lung injury induced by the cecal ligation and puncture (CLP) procedure.', 'Thirty healthy female mice were randomly divided into three groups (n = 10 each): sham operation group (control group), CLP group (CLP group), and PHC 0.45 mg/kg group (PHC group). In the PHC group, mice were given an intraperitoneal injection of PHC 0.45 mg/kg 1 h before surgery. Mice in the other two groups received an intraperitoneal injection of the same volume of normal saline. At 12 h after surgery, serum and bronchoalveolar lavage fluid were collected to examine lung permeability index. The lung tissue samples were collected to examine expressions of myosin light chain kinase (MLCK), vascular endothelial-cadherin (VE-cadherin), vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), NF-\u03baB, and beta arrestins.', 'Compared with the control group, pulmonary microvascular permeability, MPO activity, NF-\u03baB, VCAM-1, and MLCK expressions were significantly increased, whereas VE-cadherin and beta-arrestin protein expressions were obviously decreased in CLP group. Furthermore, compared with the CLP group, PHC group markedly decreased pulmonary microvascular permeability, MPO activity, NF-\u03baB, VCAM-1, and MLCK expressions, and increased expressions of VE-cadherin and beta arrestins.",
            "output": [
                "Does penehyclidine hydrochloride decrease pulmonary microvascular permeability by upregulating beta arrestins in a murine cecal ligation and puncture model?"
            ]
        },
        {
            "id": "task847-d55f2ac0d3cf40529e75f02ca5e95fe6",
            "input": "To investigate the impact of antiangiogenic monotherapy and photodynamic therapy (PDT) as add-on strategy on retinal morphology, and to analyse prognostic biomarkers for visual outcome and retreatment frequency in neovascular age-related macular degeneration (nAMD).', '255 patients participating in the MONT BLANC study were evaluated. Patients were randomised to receive as-needed ranibizumab monotherapy or combination therapy (verteporfin PDT and ranibizumab). Outcome measures included visual acuity (VA), retinal morphology assessed by optical coherence tomography and retreatment frequency.', 'The proportion of scans showing intraretinal cysts (IRC) or subretinal fluid (SRF) decreased more intensively in the combination than in the monotherapy group. Pigment epithelial detachments (PED) decreased significantly only in the combination group. Patients with IRC presented the lowest initial VA, and IRC had the strongest negative predictive value for functional improvement in both groups. SRF showed a predictive value for a higher number of ranibizumab injections (combination, +0.9; monotherapy, +0.8) and a higher number of PDT treatments in the combination group (+0.3). PED was associated with a higher number of ranibizumab injections only in the monotherapy group (+1.2).",
            "output": [
                "Are intraretinal cysts the most relevant prognostic biomarker in neovascular age-related macular degeneration independent of the therapeutic strategy?"
            ]
        },
        {
            "id": "task847-731b4fb335be42648758475f8be9b3ca",
            "input": "Poor quality of life (QoL) is a feature of people with Parkinson's disease (PD) who develop dementia. The relationship between mild cognitive impairment in PD (PD-MCI) and QoL is less clear. To address this, we studied the impact of varying severities of cognitive impairment on QoL in a cohort of non-demented patients with early PD.\", 'Patients with newly diagnosed PD (n = 219) and age and sex matched healthy controls (n = 99) completed a schedule of neuropsychological tests, in addition to scales assessing QoL (PDQ-39), depression, sleep, neuropsychiatric symptoms and a clinical examination. The Movement Disorder Society criteria were used to define and classify PD-MCI.', 'Participants with PD-MCI were significantly older than those with normal cognition, had more severe motor symptoms, scored higher for depression and had poorer quality of life. Logistic regression showed that mild cognitive impairment, independent of other factors, was an indicator of poorer QoL. Using cognitive performance 2.0 standard deviations (SD) below normative data as a cut-off to define PD-MCI, there was a significant difference in QoL scores between patients with PD-MCI and those classified as having normal cognition. Subjects with less severe mild cognitive impairment did not exhibit significant differences in QoL.",
            "output": [
                "Does severity of mild cognitive impairment in early Parkinson 's disease contribute to poorer quality of life?"
            ]
        },
        {
            "id": "task847-f6a388edaaab4487adf532a6d71ed239",
            "input": "The gene p8 was initially described in pancreatic tissue during acute experimental pancreatitis, a disease that is characterized by a systemic immune response. Although early reports suggested that p8 affects leukocyte migration during acute pancreatitis (AP), no studies revealing its immune-modulatory effects have been performed.', 'We investigated the composition of the cellular immune system in naive p8 knockout (p8(\u2212/\u2212)) mice and compared with matched wild-type mice during pancreatitis.', 'In young mice, there were no relevant differences in the composition of peripheral and splenic CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD11b(+)Gr-1(-), and Gr-1 cells. In mature p8(\u2212/\u2212) mice, increased splenic CD4CD25FoxP3 cells, spleen siderosis, and increased marginal zones in the splenic white pulp were found. During AP, peripheral and splenic CD3(+) and CD3CD4 declined stronger in the p8(\u2212/\u2212) mice. The spleen of the p8(\u2212/\u2212) mice showed severe hypoplasia of the white pulp and mild hyperplasia of the red pulp. This was associated with a significantly increased rate of apoptosis.",
            "output": [
                "Does p8 Deficiency cause siderosis in spleens and lymphocyte apoptosis in acute pancreatitis?"
            ]
        },
        {
            "id": "task847-151cd0fb922d4c1a83db4b0298a5fbaf",
            "input": "Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable.', 'We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis.', 'Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v. 13%, respectively; P = .030) and systemic recurrence (19% v. 29%, respectively; P = .027) and improved Mandard tumor regression scores (P = .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation.",
            "output": [
                "Does tumor stage after neoadjuvant chemotherapy determine survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction?"
            ]
        },
        {
            "id": "task847-8d5fe3effb5445c592ef3bad7c0f821d",
            "input": "To determine whether platelet-specific collagen receptor glycoprotein VI (GP6) gene variants are associated with recurrent miscarriages (RM).', 'Genetic association study.', 'Tertiary care referral hospital.', 'A total of 200 women with at least three unexplained spontaneous abortions before 20\\xa0weeks of gestation and 300 healthy parous women.', 'Determination of variants of GP6 single-nucleotide polymorphisms (SNPs) namely; rs1671153, rs1654410, rs1654419, and rs1613662 was based on polymerase chain reaction-restriction fragment-length polymorphism.', 'Genotypes and haplotypes frequencies were compared in RM case subjects versus control subjects.', 'We observed significantly higher occurrence of rare alleles of SNPs in GP6, namely, rs1671153, rs1654410, rs1654419, and rs1613662, among RM cases, revealing risk association for fetal losses. The synergistic effects of haplotype combinations were also evaluated and showed that four haplotypes G-T-G-G, T-C-A-A, G-C-G-A, and G-T-A-A were more prevalent among RM cases, revealing increased risk for fetal losses. In silico analysis revealed that GP6 has an impact on biologic pathways and significant influence in collagen binding. Gene-gene interaction network analysis revealed that GP6 consisted of a total of 25 interactions with 13 genes in the human genome.",
            "output": [
                "Do platelet-specific collagen receptor glycoprotein VI gene variants affect recurrent pregnancy loss?"
            ]
        },
        {
            "id": "task847-eca7a03c32cd41819b0ac5b70a2f4224",
            "input": "This study compared the pharmacokinetics of a single dose of 1% testosterone solution after application to the inner arm or the axilla as application sites for transdermal testosterone therapy.', 'Healthy, not pregnant, premenopausal women, 18 to 45 years of age with a body mass index of 20 to 28 kg/m(2) were enrolled into a single-center, open-label, randomized, 2-way crossover study. Serum total testosterone (TT), free testosterone (fT), and sex hormone binding globulin concentrations were measured. Pharmacokinetic parameters determined from serum TT and fT included area under the serum concentration versus time curve from time zero (pre-dose) until 72 hours post-dose (AUC0-72), Cmax, and Tmax. Descriptive statistics were performed on serum concentrations of TT and fT for each site. ANOVA was performed on AUC0-72 and Cmax.', 'A single-dose application of 1% testosterone solution to the inner arm and the axilla produced clear increases in TT and fT. Slower and lower increases in TT and fT were observed after treatment to the inner arm. Based on baseline-corrected AUC versus time curves, the bioavailability of 1% testosterone solution was increased 2-fold for the axilla compared with the inner arm.",
            "output": [
                "Does application site affect the pharmacokinetics of topical testosterone applied to the axilla compared with the inner arm?"
            ]
        },
        {
            "id": "task847-19a047103b94454a8dba2d174a392c0b",
            "input": "Minimally invasive parathyroidectomy for primary hyperparathyroidism is dependent on preoperative localization, commonly with ultrasound and sestamibi imaging. This study sought to determine if preoperative serum calcium and parathyroid hormone (PTH) levels correlate with localization sensitivity and positive predictive value (PPV).', 'This is a retrospective analysis of a prospective database of 1,910 patients with primary hyperparathyroidism from 2002 to 2013, who had surgeon-performed ultrasound and/or sestamibi for preoperative localization. The sensitivity and PPV of ultrasound and sestamibi were analyzed by degree of preoperative serum calcium and parathyroid hormone level perturbation.', 'In 1,910 parathyroidectomy patients, ultrasound was localizing in 1,411 of 1,644 (86%) and sestamibi in 802 of 1,165 (69%) (p < 0.01). The PPV of ultrasound was 1,135 of 1,411 (80%) and sestamibi was 705 of 802 (88%) (p < 0.01). Using logistic regression analysis, there was statistically significant positive correlation between localization and preoperative serum calcium for both sestamibi (odds ratio [OR] 1.21 [95% CI 1.00 to 1.47; p\\xa0<\\xa00.05]) and ultrasound (OR 1.29 [95% CI 1.03 to 1.60; p < 0.05]). There was a weak, but statistically significant positive correlation of PTH with sestamibi localization (OR 1.00 [95% CI 1.00 to 1.01; p < 0.05]). There was no statistically significant correlation between the PPV and serum calcium or PTH for either study. When patients were divided into quartiles of preoperative serum calcium and PTH levels, localization rates and PPV of both ultrasound and sestamibi increased with higher calcium and PTH levels. Surgeon-performed ultrasound had higher localization rates than sestamibi, with lower calcium and PTH values. Sestamibi demonstrated higher PPV values across all quartiles.",
            "output": [
                "Does the biochemical severity of primary hyperparathyroidism correlate with the localization accuracy of sestamibi and surgeon-performed ultrasound?"
            ]
        },
        {
            "id": "task847-b3a91c017e3a424485216c97cb2dca25",
            "input": "In the last decade, reactive oxygen species (ROS) production has been shown to occur upon T-cell receptor (TCR) stimulation and to affect TCR-mediated signalling. However, the exact reactive species that are produced, how ROS are generated and their requirement for T-cell activation, proliferation or cytokine production remain unclear, especially in the case of primary human T cells. Moreover, several groups have questioned that ROS are produced upon TCR stimulation.', 'To shed some light onto this issue, we specifically measured superoxide production upon TCR ligation in primary human and mouse T lymphocytes. We showed that superoxide is indeed produced and released into the extracellular space. Antioxidants, such as superoxide dismutase and ascorbate, abolished superoxide production, but surprisingly did not affect activation, proliferation and cytokine secretion in TCR-stimulated primary human T cells. It has been suggested that T cells produce ROS via the NADPH oxidase 2 (NOX2). Therefore, we investigated whether T-cell activation is affected in NOX2-deficient mice (gp91phox-/-). We found that T cells from these mice completely lack inducible superoxide production but display normal upregulation of activation markers and proliferation.",
            "output": [
                "Is tCR-triggered extracellular superoxide production required for T-cell activation?"
            ]
        },
        {
            "id": "task847-937539409fa443d593ed900538dc634d",
            "input": "To examine the in vitro effects of LL37 on the expression of vascular endothelial growth factor (VEGF) in human pulp cells and to identify the intracellular signalling pathway involved.', 'Pulp cells at passage 6 were treated with 10 \u03bcg mL(-1) synthesized LL37, and an inhibition assay was performed with MAPK or NF-\u03baB inhibitors to determine the possible signalling pathway. VEGF mRNA, VEGF protein and phosphorylated ERK1/2 levels were determined by real-time PCR, ELISA and Western blot, respectively. Data were analysed using t-tests.', 'LL37 significantly increased both the mRNA and protein levels of VEGF in pulp cells (P < 0.01). However, pre-treatment with an ERK kinase inhibitor suppressed these increases. Furthermore, the inhibitor blocked LL37-induced ERK1/2 phosphorylation.",
            "output": [
                "Does lL37 induce VEGF expression in dental pulp cells through ERK signalling?"
            ]
        },
        {
            "id": "task847-455572272e1041e995e1fe8502cd10e8",
            "input": "Two etiologic pathways of vulvar cancer are known, a human papillomavirus (HPV)- and a TP53-associated route, respectively, but other genetic changes may also play a role. Studies on somatic mutations in vulvar cancer other than TP53 are limited in number and size. In this study, we investigated the prevalence of genetic mutations in 107 vulvar squamous cell carcinomas (VSCCs).', 'A total of 107 paraffin-embedded tissue samples of primarily surgically treated VSCCs were tested for HPV infection and screened for mutations in 14 genes (BRAF, CDKN2A(p16), CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, PTEN, and TP53) using Sanger sequencing and mass spectrometry.', 'Mutations were detected in 7 genes. Of 107 VSCCs, 66 tumors (62%) contained at least one mutation (TP53=58, CDKN2A(p16)=14, HRAS=10, PIK3CA=7, PPP2R1A=3, KRAS=1, PTEN=1). Mutations occurred most frequently in HPV-negative samples. Five-year survival was significantly worse for patients with a mutation (47% vs 59%, P=.035), with a large effect from patients carrying HRAS-mutations.",
            "output": [
                "Are cDKN2A ( p16 ) and HRAS frequently mutated in vulvar squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-efe10fb0a368450d91d99b30e00f6ec7",
            "input": "To determine the association between ocular sun exposure measured by conjunctival ultraviolet (UV) autofluorescence and myopic refractive error in young adults.', 'Cross-sectional study.', 'setting: Population-based cohort in Western Australia. study population: Total of 1344 mostly white subjects aged 19-22 years in the Western Australian Pregnancy Cohort (Raine) Eye Health Study. observation procedures: Cycloplegic autorefraction, conjunctival ultraviolet autofluorescence photography, participant questionnaire. main outcome measures: Prevalence of myopic refractive error (spherical equivalent less than -0.50 diopters) and area of conjunctival ultraviolet autofluorescence in mm(2).', 'There was an inverse relationship between myopic refractive error and ocular sun exposure, with more than double the prevalence of myopia in the lowest quartile of conjunctival autofluorescence than the highest quartile (33.0% vs 15.6%). Median area of autofluorescence was significantly lower in myopic than in nonmyopic subjects (31.9 mm(2) vs 47.9 mm(2), P < .001). These differences remained significant after adjustment for age, sex, parental history of myopia, and subject level of education. The use of corrective lenses did not explain the lower conjunctival autofluorescence observed in myopic subjects.",
            "output": [
                "Is myopia in young adults inversely related to an objective marker of ocular sun exposure : the Western Australian Raine cohort study?"
            ]
        },
        {
            "id": "task847-4f30da31ccef4381a929453c165f660e",
            "input": "Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. It is also generated endogenously by lipid peroxidation and the oxidation of amino acids by myeloperoxidase. In animals, acrolein exposure is associated with the suppression of circulating progenitor cells and increases in thrombosis and atherogenesis. The purpose of this study was to determine whether acrolein exposure in humans is also associated with increased cardiovascular disease (CVD) risk.', 'Acrolein exposure was assessed in 211 participants of the Louisville Healthy Heart Study with moderate to high (CVD) risk by measuring the urinary levels of the major acrolein metabolite-3-hydroxypropylmercapturic acid (3-HPMA). Generalized linear models were used to assess the association between acrolein exposure and parameters of CVD risk, and adjusted for potential demographic confounders. Urinary 3-HPMA levels were higher in smokers than nonsmokers and were positively correlated with urinary cotinine levels. Urinary 3-HPMA levels were inversely related to levels of both early (AC133(+)) and late (AC133(-)) circulating angiogenic cells. In smokers as well as nonsmokers, 3-HPMA levels were positively associated with both increased levels of platelet-leukocyte aggregates and the Framingham Risk Score. No association was observed between 3-HPMA and plasma fibrinogen. Levels of C-reactive protein were associated with 3-HPMA levels in nonsmokers only.",
            "output": [
                "Is acrolein exposure associated with increased cardiovascular disease risk?"
            ]
        },
        {
            "id": "task847-5c072e41656b4c099413f565e2d06e22",
            "input": "Human hepatocellular carcinoma (HCC) heterogeneity promotes recurrence and resistance to therapies. Recent studies have reported that HCC may be derived not only from adult hepatocytes and hepatoblasts but also hepatic stem/progenitors. In this context, HepaRG cells may represent a suitable cellular model to study stem/progenitor cancer cells and the retrodifferentiation of tumor-derived hepatocyte-like cells. Indeed, they differentiate into hepatocyte- and biliary-like cells. Moreover, tumor-derived HepaRG hepatocyte-like cells (HepaRG-tdHep) differentiate into both hepatocyte- and biliary-like cells through a hepatic progenitor. In this study we report the mechanisms and molecular effectors involved in the retrodifferentiation of HepaRG-tdHep into bipotent progenitors. Gene expression profiling was used to identify genomic changes during the retrodifferentiation of HepaRG-tdHep into progenitors. We demonstrated that gene expression signatures related to a poor-prognosis HCC subclass, proliferative progenitors, or embryonic stem cells were significantly enriched in HepaRG progenitors derived from HepaRG-tdHep. HepaRG-tdHep retrodifferentiation is mediated by crosstalk between transforming growth factor beta 1 (TGF\u03b21) and inflammatory cytokine pathways (e.g., tumor necrosis factor alpha [TNF\u03b1] and interleukin 6 [IL6]). Signatures related to TNF\u03b1, IL6, and TGF\u03b2 activation pathways are induced within the first hour of retrodifferentiation. Moreover, specific activation or inhibition of these signaling pathways allowed us to determine that TNF\u03b1 and IL6 contribute to the loss of hepatic-specific marker expression and that TGF\u03b21 induces an epithelial-to-mesenchymal transition of HepaRG-tdHep. Interestingly, the retrodifferentiation process is blocked by the histone deacetylase inhibitor trichostatin A, opening new therapeutic opportunities.",
            "output": [
                "Do inflammatory cytokines promote the retrodifferentiation of tumor-derived hepatocyte-like cells to progenitor cells?"
            ]
        },
        {
            "id": "task847-26da31984d7e4c54aa550bb5bc5041fe",
            "input": "Various designs of braces including hinged and nonhinged models are used to provide external support of the ankle. Hinged ankle braces supposedly allow almost free dorsiflexion and plantar flexion of the foot in the sagittal plane. It is unclear, however, whether this additional degree of freedom affects the stabilizing effect of the brace in the other planes of motion.', 'To investigate the dynamic and passive stabilizing effects of 3 ankle braces, 2 hinged models that provide free plantar flexion-dorsiflexion in the sagittal plane and 1 ankle brace without a hinge.', 'Crossover study.', 'University Movement Analysis Laboratory.', 'Seventeen healthy volunteers (5 women, 12 men; age = 25.4 \u00b1 4.8 years; height = 180.3 \u00b1 6.5 cm; body mass = 75.5 \u00b1 10.4 kg).', 'We dynamically induced foot inversion on a tilting platform and passively induced foot movements in 6 directions via a custom-built apparatus in 3 brace conditions and a control condition (no brace).', 'Maximum inversion was determined dynamically using an in-shoe electrogoniometer. Passively induced maximal joint angles were measured using a torque and angle sensor. We analyzed differences among the 4 ankle-brace conditions (3 braces, 1 control) for each of the dependent variables with Friedman and post hoc tests (P < .05).', 'Each ankle brace restricted dynamic foot-inversion movements on the tilting platform as compared with the control condition, whereas only the 2 hinged ankle braces differed from each other, with greater movement restriction caused by the Ankle X model. Passive foot inversion was reduced with all ankle braces. Passive plantar flexion was greater in the hinged models as compared with the nonhinged brace.",
            "output": [
                "Does biomechanical comparison of 3 ankle brace with and without free rotation in the sagittal plane?"
            ]
        },
        {
            "id": "task847-cb9a0826f04f4254b071a8034ee3d3b2",
            "input": "Remission, the primary goal of treatment for major depressive disorder (MDD), is the absence of significant signs or symptoms and the return to a state of normal functioning. A recent study found that the level of brain-derived neurotrophic factor (BDNF) increased after antidepressant treatment in remitted patients. This study evaluated serum BDNF levels in MDD patients with chronic maintenance treatment, and compared these between remission and nonremission groups.', 'Serum BDNF levels were measured in 34 MDD patients and 35 healthy controls. The severity of depression was measured using the Hamilton Depression Rating Scale (Ham-D). The MDD patients were divided into remission and nonremission groups according to a cutoff total Ham-D score of either \u22647 or \u22646.', 'Serum BDNF levels differed significantly between the remission, nonremission, and healthy control groups (P<0.05). The Bonferroni post hoc test confirmed that serum BDNF levels were significantly lower in the nonremission group than in the healthy-control group (P<0.05), but did not differ significantly between the remission and healthy-control groups.",
            "output": [
                "Are lower serum brain-derived neurotrophic factor levels associated with failure to achieve remission in patients with major depression after escitalopram treatment?"
            ]
        },
        {
            "id": "task847-4ae45967a4c54f85b63c87252180c385",
            "input": "Cerebral ischemia upregulates aquaporin-4 expression, increases blood-brain barrier (BBB) permeability, and induces brain edema. Mesenchymal stem cells (MSCs) can repress inflammatory cytokines and show great potential for ischemic stroke therapy. However, the effect of MSCs regarding the protection of ischemia-induced BBB break down is unknown.', 'We test whether MSCs therapy protects BBB integrity and explore the molecular mechanisms of aquaporin-4 on BBB integrity.', 'Two hundred and twenty-eight adult CD1 male mice underwent 90 minutes transient middle cerebral artery occlusion and received 2 \u00d7 10(5) MSCs intracranial transplantation. The neurological severity score was improved and both ischemia-induced brain edema and BBB leakage were reduced in MSC-treated mice. MSCs therapy reduced astrocyte apoptosis and inhibited ischemia-induced aquaporin-4 upregulation. In addition, small-interfering RNA knockdown of aquaporin-4 after cerebral ischemia effectively reduced aquaporin-4 expression, brain edema, BBB leakage, and astrocyte apoptosis. Conditional medium from lipopolysaccharide (LPS)-activated microglia enhanced aquaporin-4 expression, p38 and JNK phosphorylation, and apoptosis of cultured astrocytes. MSC treatment reduced the expression of inflammatory cytokines in LPS-activated microglia, and subsequently reduced aquaporin-4 expression and apoptosis of astrocytes. Knockdown of aquaporin-4 in cultured astrocytes also reduced apoptosis. Treatment with p38 and JNK inhibitors showed that p38, but not the JNK signaling pathway, was responsible for the aquaporin-4 upregulation.",
            "output": [
                "Do mesenchymal stem cells maintain blood-brain barrier integrity by inhibiting aquaporin-4 upregulation after cerebral ischemia?"
            ]
        },
        {
            "id": "task847-c55da4aa2df642eabd5a94bd18fc0d93",
            "input": "Two-dimensional speckle tracking echocardiography (2DSTE) has been used widely in research, but rarely in clinical practice because data acquisition and analysis are time-consuming. By reducing the acquisition and analysis time, 3-dimensional STE may improve clinical impact. We investigated the feasibility of 3DSTE myocardial deformation, with comparison to 2DSTE.', 'Transthoracic 3DSTE and 2DSTE were performed in 230 adults (138 men, 51 \u00b1 14 years, and 142 hypertension, 10 heart failure and 78 normotensive subjects). The variables of LV deformation were analyzed using EchoPAC software.', 'The 3D LV longitudinal (LS) analysis was feasible in 84.9% of the study subjects, which was lower than the 2D analysis (97.2%). The success rates for circumferential strain (CS) and radial strain (RS) were similar between the 2D and 3D techniques. All magnitude of strains measured by 2DSTE and 3DSTE were significantly correlated. The magnitude of 3D LS and CS was lower, but the 3D RS is higher than that of 2DSTE (-18.5 \u00b1 2.8 vs. -21.2 \u00b1 3.5; 20.8 \u00b1 4.1 vs. 21.7; and 50.0 \u00b1 11.2 vs. 37.7 \u00b1 12.6, respectively). Strains measured by 3DSTE exhibited stronger correlation with LV ejection fraction (EF) than that by 2DSTE. In inter- and intra-observer reproducibility for 3D LS, CS, RS and AS were acceptable. The mean time of analysis for LV volume, EF and strains was 116s by 3DSTE, which was significantly shorter than that by 2DSTE (5 min, P<0.0001).",
            "output": [
                "Is three-dimensional speckle strain echocardiography more accurate and efficient than 2D strain in the evaluation of left ventricular function?"
            ]
        },
        {
            "id": "task847-df51fe1b294840c192f2e633dbde6aa0",
            "input": "To compare single- with double-layer closure of the uterus for the risk of uterine rupture in women attempting vaginal birth after one prior caesarean delivery.', 'Cohort study.', 'Sweden.', 'From a total of 19\\xa0604 nulliparous women delivered by caesarean section in the years 2001-2007, 7683 women attempting vaginal birth in their second delivery were analysed.', 'Data from population-based registers were linked to hospital-based registers that held data from maternity and delivery records. Logistic regression was used to estimate the risk of uterine rupture after single- or double-layer closure of the uterus. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs).', 'Uterine rupture.', 'Uterine rupture during labour occurred in 103 (1.3%) women. There was no increased risk of uterine rupture when single- was compared with double-layer closure of the uterus (OR\\xa01.17; 95% CI 0.78-1.76). Maternal factors associated with uterine rupture were: age \u226535\\xa0years and height \u2264160\\xa0cm. Factors from the first delivery associated with uterine rupture in a subsequent delivery were: infection and giving birth to an infant large for gestational age. Risk factors from the second delivery were induction of labour, use of epidural analgesia, and a birthweight of \u22654500\\xa0g.",
            "output": [
                "Is the risk of uterine rupture increased with single- compared with double-layer closure : a Swedish cohort study?"
            ]
        },
        {
            "id": "task847-0ae09c14db8d4ec38a6d7b8f99a401b1",
            "input": "Mannose-binding lectin (MBL) is a protein of the innate immune system that participates in host defense and the tissue injury/repair process, enhancing the clearance of apoptotic cells by macrophages. The aim is to characterize the relationship between pre-transplant MBL levels, histological lesions and number of apoptotic cells in early surveillance renal allograft biopsies.', 'Consecutive renal transplant recipients were recruited and MBL levels were classified into tertiles. The first tertile was considered the low MBL group. Surveillance biopsies were done during the first 6 months and were evaluated according to Banff criteria. Renal inflammatory infiltrates were studied by immunohistochemical techniques. Apoptosis was studied using morphological methods in renal tubular cells and was expressed as the number of apoptotic cells/mm(2).', 'MBL was determined in 126 patients and a surveillance biopsy with sufficient tissue was obtained in 41 of them. Patients with low pre-transplant MBL levels showed a higher acute Banff index (3.14 \u00b1 1.96 vs. 1.88 \u00b1 1.56, p = 0.044) and an increased proportion of biopsies with tubular cell apoptosis The proportion of biopsies with tubular cell apoptosis was higher in patients with low pre-transplant MBL levels in comparison with patients with high MBL levels (4.3 \u00b1 3.6 versus 0.2 \u00b1 0.9 p = 0.012) and increased interstitial number of inflammatory cells and significantly the macrophages/mm(2) (109 \u00b1 118 vs. 32 \u00b1 46; p = 0.04).",
            "output": [
                "Are low serum mannose-binding lectin levels associated with inflammation and apoptosis in early surveillance allograft biopsies?"
            ]
        },
        {
            "id": "task847-193f4d0c014b44dda71509dfa9ced80f",
            "input": "C-reactive protein (CRP) levels predict incident and recurrent cardiovascular disease (CVD) events; however, associations between CRP and pre-clinical atherosclerosis is less certain. Since high concentrations of high-density lipoprotein cholesterol (HDL-C) are inversely associated with CVD risk, we investigated whether HDL-C modified the association between CRP concentration and measures of preclinical atherosclerosis.', 'Data were analyzed from a Korean occupational cohort of 12,030 male subjects who underwent a cardiac computed tomography (CT) estimation of coronary artery calcification (CAC) score and an assessment of CVD risk factors. Logistic regression was used to describe associations between CRP and measures of pre-clinical atherosclerosis, such as CAC scores >0. As many as 1351 (11.2%) participants had a CAC score>0. CRP was stratified into 3 groups based on clinical category: <1 mg/L, 1 to <2 mg/L, and \u2265 2 mg/dL. In the bottom CRP group, 907/8697 (10.4%) of subjects had a CAC score >0, compared with 242/1943 (12.5%) in the middle group and 202/1396 (14.5%) in the top CRP group (p < 0.0001). After adjustment for multiple CVD risk factors, there was a positive association between CRP and CAC score>0 (OR between top and bottom CRP groups, 1.41 [1.04, 1.90], p = 0.027) in the lowest HDL-C quartile but not in the highest HDL-C (OR between top and bottom CRP group, 0.80 [0.46, 1.39], p = 0.425).",
            "output": [
                "Do hDL-C levels modify the association between C-reactive protein and coronary artery calcium score?"
            ]
        },
        {
            "id": "task847-8d819a51555f44748c6a2f352be8767e",
            "input": "The COMFORT behaviour scale (COMFORT-B scale) is widely used in paediatric intensive care units to assess young children's pain and distress. It is also used to assess the impact of treatment interventions, but little is known on the scale's sensitivity to detect changes between before and after measurements following an intervention. This study explored the sensitivity to change of the COMFORT-B scale.\", 'COMFORT-B scores, originally and prospectively collected as part of standard care, were retrieved from the digital patient data management system. We analysed scores obtained in 747 paired observations, i.e., before and after a pharmacological intervention in 180 paediatric intensive care patients between September 2009 and September 2010.', 'The mean scores before and after an intervention were 20.0 [standard deviation (SD) 3.7] and 14.1 (SD 4.7), respectively. Multilevel regression analysis showed a 6-point mean decline after an intervention (p\\u2009<\\u20090.0001). The magnitude of this decline was not statistically significantly related to number and type of interventions or time between assessments. In almost three-quarters of cases (74%), the COMFORT-B score dropped to below 17 after a pharmacological intervention, indicating good responsiveness.",
            "output": [
                "Does the COMFORT behaviour scale detect clinically meaningful effects of analgesic and sedative treatment?"
            ]
        },
        {
            "id": "task847-02a0463f0747418ca4045f91c9f02ca3",
            "input": "With rising obesity rates in children, it is increasingly difficult to differentiate between type 1 and type 2 diabetes mellitus (T1DM, T2DM) on clinical grounds alone. Using C-peptide as a method of classifying diabetes mellitus (DM) has been suggested. This study aimed to find a correlation between fasting C-peptide level and DM types in children and adolescents.', 'A total of 223 diabetic children, newly diagnosed at 5 hospitals between January 2001 and December 2012, were enrolled in this study. Initial DM classification was based on clinical and laboratory data including fasting C-peptide at diagnosis; final classification was based on additional data (pancreatic autoantibodies, human leukocyte antigen type, and clinical course).', 'Of 223 diabetic children, 140 were diagnosed with T1DM (62.8%) and the remaining 83 with T2DM (37.2%). The mean serum C-peptide level was significantly lower in children with T1DM (0.80 ng/mL) than in children with T2DM (3.91 ng/mL). Among 223 children, 54 had a serum C-peptide level <0.6 ng/mL; they were all diagnosed with T1DM. The proportion of children with T2DM increased in accordance with C-peptide level. Forty-nine of 223 children had a C-peptide level >3.0 ng/mL; 48 of them (97.9%) were diagnosed with T2DM.",
            "output": [
                "Is fasting serum C-peptide useful for initial classification of diabetes mellitus in children and adolescents?"
            ]
        },
        {
            "id": "task847-a477f5be94314a519dd2e52a0cfc1390",
            "input": "BRAT1 (BRCA1-associated ATM activator 1) interacts with both BRCA1, ATM and DNA-PKcs, and has been implicated in DNA damage responses. However, based on our previous results, it has been shown that BRAT1 may be involved in cell growth and apoptosis, besides DNA damage responses, implying that there are undiscovered functions for BRAT1.', 'Using RNA interference against human BRAT1, we generated stable BRAT1 knockdown cancer cell lines of U2OS, Hela, and MDA-MA-231. We tested cell growth properties and in vitro/in vivo tumorigenic potentials of BRAT1 knockdown cells compared to control cells. To test if loss of BRAT1 induces metabolic abnormalities, we examined the rate of glycolysis, ATP production, and PDH activity in both BRAT1 knockdown and control cells. The role of BRAT1 in growth signaling was determined by the activation of Akt/Erk, and SC79, Akt activator was used for validation.', 'By taking advantage of BRAT1 knockdown cancer cell lines, we found that loss of BRAT1 expression significantly decreases cell proliferation and tumorigenecity both in vitro and in vivo. Cell migration was also remarkably lowered when BRAT1 was depleted. Interestingly, glucose uptake and production of mitochondrial ROS (reactive oxygen species) are highly increased in BRAT1 knockdown HeLa cells. Furthermore, both basal and induced activity of Akt and Erk kinases were suppressed in these cells, implicating abnormality in signaling cascades for cellular growth. Consequently, treatment of BRAT1 knockdown cells with Akt activator can improve their proliferation and reduces mitochondrial ROS concentration.",
            "output": [
                "Does bRAT1 deficiency cause increased glucose metabolism and mitochondrial malfunction?"
            ]
        },
        {
            "id": "task847-2e8077dc524a4ee69f3df7eff5d0e2d7",
            "input": "Sophocarpine, a tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L., has been documented that it can suppress pro-inflammatory cytokines synthesis in alleviating nonalcoholic steatohepatitis (NASH) in vivo. Toll-like receptor 4 (TLR4) is a pattern recognition receptor whose activation results in the production of several pro-inflammatory cytokines. It has been reported that TLR4 is upregulated in nonalcoholic fatty liver disease and plays an important role in the pathogenesis of NASH. This study aimed to examine the changes of TLR4 and its signaling pathways in sophocarpine's anti-inflammatory process on experimental NASH\\u2005in vitro.\", 'Primary hepatocytes were isolated, and oleic acid-induced steatosis model was established. Cell Counting Kit-8 assay was used to detect the number of metabolically active mitochondria and viable cells. Immunocytochemistry analysis was applied to evaluating pro-inflammatory cytokines synthesis. Total RNA and protein were extracted for real-time polymerase chain reaction and Western blot detection.', 'Enhanced expression of TLR4 was observed in oleic acid-induced steatotic hepatocytes. Sophocarpine suppressed pro-inflammatory cytokines synthesis and reduced the expression of TLR4 in steatotic hepatocytes. Expression of TLR4 and pro-inflammatory cytokines recovered after sophocarpine was removed. Moreover, sophocarpine restrained the activation of nuclear factor-kappaB (NF-\u03baB), c-Jun-N-terminal kinase (JNK), and Extracellular regulated protein kinases (ERK) signaling pathways in the anti-inflammatory process.",
            "output": [
                "Does sophocarpine attenuate toll-like receptor 4 in steatotic hepatocytes to suppress pro-inflammatory cytokines synthesis?"
            ]
        },
        {
            "id": "task847-c9e37fb6a3d7492695baf0ba3c11fd8c",
            "input": "Hypocalcemia is the most common complication after total thyroidectomy. Some patients need to stay in the hospital for monitoring of hypocalcemic symptoms and serum calcium levels for several days. We investigated the efficacy and safety of using early postoperative parathyroid hormone (PTH) results for early discharge after thyroidectomy.', 'A retrospective cohort study of 2 sequential groups of patients undergoing total thyroidectomy between January 2010 and March 2013 was undertaken. Patients were divided into 2 groups. In Group 1 (before June 2011), patients had daily monitoring of serum calcium level and hypocalcemic symptoms. They were discharged when calcium level was static and asymptomatic. Postoperative PTH was not utilized for discharge plan. In Group 2 (after June 2011), postoperative PTH and calcium level on day 1 were utilized to dictate subsequent management and discharge plan.', 'Of the 107 patients reviewed, 54 (50.5%) were in Group 1 and 53 (49.5%) were in Group 2. A total of 51 (47.7%) patients developed hypocalcemia. The two groups were comparable in demographic data, early postoperative PTH value, rate of hypocalcemia, the need for oral calcium and vitamin D supplements and rate of permanent hypoparathyroidism. Fewer patients in Group 2 experienced hypocalcemic symptoms, p=0.005. None of the patients in Group 2 needed intravenous calcium supplement (p=0.003). The median postoperative hospital stay for Group 1 was 4 days and for Group 2 was 1 day (p<0.0001).",
            "output": [
                "Does postoperative PTH monitoring of hypocalcemia expedite discharge after thyroidectomy?"
            ]
        },
        {
            "id": "task847-e8844da672644d28b513044a9ce99396",
            "input": "Single-incision laparoscopic colectomy (SILC) is one of several promising operation choices. Our previous study demonstrated that SILC with a self-made glove-port system both improves the feasibility of SILC and decreases the cost expense of surgery. Because the incision site for SILC could be made at either the umbilicus or McBurney's point, we are interested in whether the incision site affects the outcomes of patients, which is a less explored topic. The purpose of this study is not only to show the results of SILC with a self-made glove-port system for supporting its feasibility, but also to compare the short-term surgical outcomes between SILC with the incision made at the umbilicus and at McBurney's point.\", \"We collected and reviewed the medical records of patients who received SILC with a self-made glove-port system for tumors in the left side of the colon from August 2009 to March 2011. All operations were performed by a single surgeon. Comparisons of the demographic characteristics, perioperative data, and clinical outcomes between umbilical and McBurney's SILCs were performed. Postoperative pain was assessed by a visual analog scale and opiate demand.\", \"In total, 61 patients were enrolled in this retrospective study. Five of 48 (10.4%) tumors in the umbilical SILC group and 5 of 13 (38.5%) tumors in the McBurney's SILC group were located below the peritoneal reflection. The tumor location was significantly different between these two groups (P=.015). Patients in the umbilical SILC group had significantly higher frequency of opiate demand than those in the McBurney's SILC group (0.4\u00b10.7 versus 1.4\u00b11.8, respectively; P=.002).",
            "output": [
                "Does the application of McBurney 's single-incision laparoscopic colectomy alleviate the response of patients to postoperative wound pain?"
            ]
        },
        {
            "id": "task847-27d2dd9f88444ec1a23b207de987b887",
            "input": "Bortezomib-induced peripheral neuropathy (BIPN) is a significant neurotoxicity, requiring dose reduction or the delay of treatment. In a multicentre trial including 97 % Caucasians and 3 % Asians, BIPN was shown to occur less frequently in cases in which bortezomib was administered subcutaneously. Considering the different pharmacokinetics between Caucasians and Asians, we analysed BIPN according to the administration route, specifically in Korean myeloma patients.', 'We surveyed the prescribed anticonvulsants for the treatment of BIPN and analysed the data after stratifying the results by the cumulative dose of bortezomib. Exclusion criteria were as follows: treated with <2 doses of bortezomib, change in the administration route during the treatment, or receiving anticonvulsants for other reasons prior to bortezomib administration.', 'A total of 101 patients were enrolled; 60 were treated with bortezomib and dexamethasone, and 37 were treated with bortezomib, melphalan, and prednisolone. The median number of treatment courses was four for each regimens. The median exposure to bortezomib for all patients was 19 mg/m(2). Progression-free survival (PFS) and overall survival rates were not statistically different between the groups. There was no difference in the proportion of patients requiring medical treatment (p = 0.388). After stratifying the results, BIPN developed less frequently when bortezomib was administered subcutaneously rather than intravenously in patients receiving more than 23.4 mg/m(2) of bortezomib (p < 0.05).",
            "output": [
                "Is bortezomib-associated peripheral neuropathy requiring medical treatment decreased by administering the medication by subcutaneous injection in Korean multiple myeloma patients?"
            ]
        },
        {
            "id": "task847-b1102838b8954353ac68377afc5b2207",
            "input": "Effective therapeutic interventions for chronic, idiopathic lung diseases remain elusive. Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important inhibitors of T-cell function.', 'To determine the effects of PD-1 pathway blockade on sarcoidosis CD4(+) T-cell proliferative capacity.', 'Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage-derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. Immunohistochemistry analysis for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy control lung specimens.', 'Microarray analysis demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis peripheral blood mononuclear cells. Immunohistochemistry analysis revealed increased PD-L1 expression within sarcoidosis granulomas and lung malignancy, but this was absent in healthy lungs. Increased numbers of sarcoidosis PD-1(+) CD4(+) T cells are present systemically, compared with healthy control subjects (P < 0.0001). Lymphocytes with reduced proliferative capacity exhibited increased proliferation with PD-1 pathway blockade. Longitudinal analysis of subjects with sarcoidosis revealed reduced PD-1(+) CD4(+) T cells with spontaneous clinical resolution but not with disease progression.",
            "output": [
                "Does blockade of the programmed death-1 pathway restore sarcoidosis CD4 ( + ) T-cell proliferative capacity?"
            ]
        },
        {
            "id": "task847-9f281f5293dd413e8fbfc1c38e2f7601",
            "input": "Despite recent advancements in post-cardiac arrest resuscitation, the optimal measurement of postarrest outcome remains unclear. We hypothesized that Cerebral Performance Category score can predict the long-term outcome of postarrest survivors who received targeted temperature management during their postarrest hospital care.', 'Retrospective chart review.', 'Two academic medical centers from May 2005 to December 2012.', 'The medical records of 2,417 out-of-hospital and in-hospital patients post cardiac arrest were reviewed to identify 140 of 582 survivors who received targeted temperature management.', 'None.', 'The Cerebral Performance Category scores at hospital discharge were determined by three independent abstractors. The 1-month, 6-month, and 12-month survival of these patients was determined by reviewing hospital records and querying the Social Security Death Index and by follow-up telephone calls. The association of unadjusted long-term survival and adjusted survival with Cerebral Performance Category was calculated. Of the 2,417 patients who were identified to have undergone cardiac arrest, 24.1% (582/2,417) were successfully resuscitated, of whom 24.1% (140/582) received postarrest targeted temperature management. Overall, 42.9% of patients (60/140) were discharged with Cerebral Performance Category 1, 27.1% (38/140) with Cerebral Performance Category 2, 18.6% (26/140) with Cerebral Performance Category 3, and 11.4% (16/140) with Cerebral Performance Category 4. Cerebral Performance Category 1 survivors had the highest long-term survival followed by Cerebral Performance Categories 2 and 3, with Cerebral Performance Category 4 having the lowest long-term survival (p < 0.001, log-rank test). We found that Cerebral Performance Category 3 (hazard ratio = 3.62, p < 0.05) and Cerebral Performance Category 4 (hazard ratio = 12.73, p < 0.001) remained associated with worse survival after adjusting for age, gender, race, shockable rhythm, time to targeted temperature management initiation, total duration of resuscitation, withdrawal of care, and location of arrest.",
            "output": [
                "Does cerebral performance category at hospital discharge predict long-term survival of cardiac arrest survivors receiving targeted temperature management*?"
            ]
        },
        {
            "id": "task847-feb0597d8907439c9c6fcf0b06087b04",
            "input": "To determine the impact of prostate size on positive surgical margin (PSM) rates after robot-assisted radical prostatectomy (RARP) and the preoperative factors associated with PSM.', 'In all, 1229 men underwent RARP by a single surgeon, from 2005 to August of 2013. Excluded were patients who had transurethral resection of the prostate, neoadjuvant therapy, clinically advanced cancer, and the first 200 performed cases (to reduce the effect of learning curve). Included were 815 patients who were then divided into three prostate size groups: <31\\u2009g (group 1), 31-45\\u2009g (group 2), >45\\u2009g (group 3). Multivariate analysis determined predictors of PSM and biochemical recurrence (BCR).', 'Console time and blood loss increased with increasing prostate size. There were more high-grade tumours in group 1 (group 1 vs group 2 and group 3, 33.9% vs 25.1% and 25.6%, P = 0.003 and P = 0.005). PSM rates were higher in prostates of <45\\u2009g with preoperative PSA levels of >20\\u2009ng/dL, Gleason score \u22657, T3 tumour, and \u22653 positive biopsy cores. In group 1, preoperative stage T3 [odds ratio (OR) 3.94, P = 0.020] and \u22653 positive biopsy cores (OR 2.52, P = 0.043) were predictive of PSM, while a PSA level of >20\\u2009ng/dL predicted the occurrence of BCR (OR 5.34, P = 0.021). No preoperative factors predicted PSM or BCR for groups 2 and 3.",
            "output": [
                "Is number of positive preoperative biopsy cores a predictor of positive surgical margins ( PSM ) in small prostates after robot-assisted radical prostatectomy ( RARP )?"
            ]
        },
        {
            "id": "task847-e3e8cfc6924f4070b51ba0d1b3e7581c",
            "input": "Targeting the energy storing white adipose tissue (WAT) by pharmacological and dietary means in order to promote its conversion to energy expending \"brite\" cell type holds promise as an anti-obesity approach. Present study was designed to investigate/revisit the effect of capsaicin on adipogenic differentiation with special reference to induction of \"brite\" phenotype during differentiation of 3T3-L1 preadipocytes.', 'Multiple techniques such as Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and matured adipocytes have been employed to understand the effect of capsaicin at different doses. In addition to in-vitro experiments, in-vivo studies were carried out in high-fat diet (HFD) fed rats treated with resiniferatoxin (RTX) (a TRPV1 agonist) and in mice administered capsaicin.', 'TRPV1 channels are expressed in preadipocytes but not in adipocytes. In preadipocytes, both capsaicin and RTX stimulate Ca2+ influx in dose-dependent manner. This stimulation may be prevented by capsazepine, a TRPV1 antagonist. At lower doses, capsaicin inhibits lipid accumulation and stimulates TRPV1 gene expression, while at higher doses it enhances accumulation of lipids and suppresses expression of its receptor. In doses of 0.1-100 \u00b5M, capsaicin promotes expression of major pro-adipogenic factor PPAR\u03b3 and some of its downstream targets. In concentrations of 1 \u00b5M, capsaicin up-regulates anti-adipogenic genes. Low-dose capsaicin treatment of 3T3-L1 preadipocytes differentiating into adipocytes results in increased expression of brown fat cell marker genes. In white adipose of mice, capsaicin administration leads to increase in browning-specific genes. Global TRPV1 ablation (i.p. by RTX administration) leads to increase in locomotor activity with no change in body weight.",
            "output": [
                "Does capsaicin induce `` brite '' phenotype in differentiating 3T3-L1 preadipocytes?"
            ]
        },
        {
            "id": "task847-b41b2a88217341908d759ca904252aaa",
            "input": "Cytochrome c (Cyt c) is an apoptosis-initiating protein when released into the cytoplasm of eukaryotic cells and therefore a possible cancer drug candidate. Although proteins have been increasingly important as pharmaceutical agents, their chemical and physical instability during production, storage, and delivery remains a problem. Chemical glycosylation has been devised as a method to increase protein stability and thus enhance their long-lasting bioavailability.', 'Three different molecular weight glycans (lactose and two dextrans with 1 kD and 10 kD) were chemically coupled to surface exposed Cyt c lysine (Lys) residues using succinimidyl chemistry via amide bonds. Five neo-glycoconjugates were synthesized, Lac4-Cyt-c, Lac9-Cyt-c, Dex5(10kD)-Cyt-c, Dex8(10kD)-Cyt-c, and Dex3(1kD)-Cyt-c. Subsequently, we investigated glycoconjugate structure, activity, and stability. Circular dichroism (CD) spectra demonstrated that Cyt c glycosylation did not cause significant changes to the secondary structure, while high glycosylation levels caused some minor tertiary structure perturbations. Functionality of the Cyt c glycoconjugates was determined by performing cell-free caspase 3 and caspase 9 induction assays and by measuring the peroxidase-like pseudo enzyme activity. The glycoconjugates showed \u226594% residual enzyme activity and 86 \u00b1 3 to 95 \u00b1 1% relative caspase 3 activation compared to non-modified Cyt c. Caspase 9 activation by the glycoconjugates was with 92 \u00b1 7% to 96 \u00b1 4% within the error the same as the caspase 3 activation. There were no major changes in Cyt c activity upon glycosylation. Incubation of Dex3(1 kD)-Cyt c with mercaptoethanol caused significant loss in the tertiary structure and a drop in caspase 3 and 9 activation to only 24 \u00b1 8% and 26 \u00b1 6%, respectively. This demonstrates that tertiary structure intactness of Cyt c was essential for apoptosis induction. Furthermore, glycosylation protected Cyt c from detrimental effects by some stresses (i.e., elevated temperature and humidity) and from proteolytic degradation. In addition, non-modified Cyt c was more susceptible to denaturation by a water-organic solvent interface than its glycoconjugates, important for the formulation in polymers.",
            "output": [
                "Does chemical glycosylation of cytochrome c improve physical and chemical protein stability?"
            ]
        },
        {
            "id": "task847-e3f26f1141204512bb5def634c695993",
            "input": "ErbB family receptor tyrosine kinases (ErbBs) play a role in cell adhesion and migration and are frequently overexpressed in esophageal squamous cell carcinomas (ESCCs) or esophageal adenocarcinomas (EACs). Targeting ErbBs by tyrosine kinase inhibitors (TKIs) may therefore limit esophageal cancer cell migration. Here, we studied the impact of TKIs on ErbB dimerization, cell signaling pathways, and cell migration in three esophageal cell lines: OE21 (ESCC), OE33 (EAC), and Het-1A (non-neoplastic esophageal epithelium). In OE21 cells, the TKIs erlotinib, gefitinib, and lapatinib slightly affected epidermal growth factor receptor EGFR/EGFR, but not EGFR/HER2 dimerization as detected by in situ proximity ligation assay (in situ PLA). Still, TKIs inhibited ERK1/2, Akt, STAT3, and RhoA activity in OE21 cells, as assessed by Western blot, antibody arrays, and Rho GTPase effector pull-down assays. This was accompanied by reduced OE21 cell migration, induction of focal adhesions, and actin cytoskeleton reorganization, as shown by Oris\u2122 migration assay and focal adhesion kinase (FAK)/phalloidin staining. In contrast, in OE33 cells, only lapatinib decreased STAT5, Src family kinase (SFK), and FAK activity as well as \u03b2-catenin expression. This impeded cell migration and induced morphological changes in OE33 cells. No alterations were seen for the non-neoplastic Het-1A cells. Thus, we identified the ErbB signaling network as regulator of esophageal cancer cell's actin cytoskeleton, focal adhesions, and cell migration. ErbB targeted TKIs therefore also limit ESCC and EAC cell motility and migration.",
            "output": [
                "Do erbB targeting inhibitors repress cell migration of esophageal squamous cell carcinoma and adenocarcinoma cells by distinct signaling pathways?"
            ]
        },
        {
            "id": "task847-c7a77b8c65154a21abf08b0dc6fefe6e",
            "input": "Hyperhomocysteinemia (HHcy) is associated with kidney disease and leads to atherosclerosis and thrombosis. Paraoxonase 1 (Pon1), a hydrolase that participates in homocysteine (Hcy) metabolism and is carried in the circulation on high-density lipoprotein, has also been linked to kidney disease and atherothrombosis. Pon1-knockout mice are susceptible to atherosclerosis and exhibit a kidney-associated phenotype, polyuria or urine dilution. We hypothesize that HHcy and Pon1 deficiency are toxic to kidney function because they impair metabolic pathways important for normal kidney homeostasis.', 'We examined changes in the mouse kidney proteome induced by Pon1 gene deletion and dietary HHcy, using 2D IEF/SDS-PAGE gel electrophoresis and MALDI-TOF mass spectrometry. We found that the expression of ten mouse kidney proteins was altered by the Pon1(-/-) genotype or HHcy. Proteins involved in metabolism of lipid (ApoA-I), protein (Hspd1), carbohydrate (Pdhb, Fbp1-isoform2, Eno1), and energy (Ndufs8, Ldhd) were down-regulated. Proteins involved in lipid transport (Pebp1), oxidative stress response (Prdx2), and cellular detoxification (Glo1) were up-regulated. The kidney proteins altered by HHcy or Pon1 are also altered in renal disease.",
            "output": [
                "Do paraoxonase 1 deficiency and hyperhomocysteinemia alter the expression of mouse kidney proteins involved in renal disease?"
            ]
        },
        {
            "id": "task847-d671c8f31b3946739ca9ace698c7f84a",
            "input": "Endophytic bacteria do have several potential applications in medicine and in other various sectors of biotechnology including agriculture. Bacterial endophytes need to be explored for their potential applications in agricultural biotechnology. One of the potential applications of bacterial endophytes in agricultural is to enhance the growth of the agricultural crops. Hence, this study was undertaken to explore the plant growth promoting potential application of bacterial endophytes.', 'The objective of this study was to examine the effect of endophytic bacteria from mangrove tree (Rhizophora apiculata Blume) for their efficacy in promoting seedling growth in rice.', 'Eight endophytic bacterial isolates (EBIs) isolated from twig and petiole tissues of the mangrove were identified based on their 16S ribosomal ribonucleic acid (rRNA) gene sequence homology. Separately, surface sterilized paddy seeds were treated with cell-free broth and cell suspension of the EBIs. Rice seedlings were analyzed by various bioassays and data was recorded.', 'The gene sequences of the isolates were closely related to two genera namely, Bacillus and Pantoea. Inoculation of EBIs from R. apiculata with rice seeds resulted in accelerated root and shoot growth with significant increase in chlorophyll content. Among the isolates, Pantoea ananatis (1MSE1) and Bacillus amyloliquefaciens (3MPE1) had shown predominance of activity. Endophytic invasion was recognized by the non-host by rapid accumulation of reactive oxygen species (ROS) and was counteracted by the production of hydrogen peroxide (H2O2) and lipid peroxide. The results demonstrated that EBIs from mangrove tree can increase the fitness of the rice seedlings under controlled conditions.",
            "output": [
                "Do culturable bacterial endophytes isolated from Mangrove tree ( Rhizophora apiculata Blume ) enhance seedling growth in Rice?"
            ]
        },
        {
            "id": "task847-6f53c859b7ff45c4902374eeca664536",
            "input": "This study is to investigate the mechanisms by which macrophage-activating lipopeptide-2 (MALP-2) induces heme oxygenase (HO)-1, a cytoprotective enzyme that catalyzes the degradation of heme, in human monocytes.', 'Human monocytic THP-1 cells were cultured for transient transfection with plasmids and stimulation with MALP-2 for indicative time intervals. After incubation with MALP-2, cells were collected and disrupted, before being tested for promoter activity using luciferase assay. For analysis of proteins, immunoreactive bands were detected using an enhanced chemiluminescence Western blotting system, and the band intensity was measured by densitometryic analysis. For the detection of co-immunoprecipitation, SDS-PAGE was performed and the membranes were probed using respective antibodies. To investigate the cellular localization of NF-E2-related factor 2 (Nrf2), cells underwent immunofluorescence staining and confocal microscopy, and were analyzed using electrophoretic mobility shift assay.', 'MALP-2-induced HO-1 expression and promoter activity were abrogated by transfection with dominant negative (DN) plasmids of TLR2 and TLR6, or their neutralizing antibodies. However, inhibition of MyD88 or transfection with the DN-MyD88 was insufficient to attenuate HO-1 expression. In contrast, mutation or silencing of MyD88 adapter-like (Mal) by DN-Mal or siRNA almost completely blocked HO-1 induction. Btk, c-Src and PI3K were also involved in MALP-2-induced HO-1 expression, as revealed by specific inhibitors LFM-A13, PP1 and LY294002, or by transfection with siRNA of c-Src. MALP-2-induced activation of PI3K was attenuated by transfection with DN mutant of Mal, and by pretreatment with LFM-A13 or PP1. Furthermore, MALP-2 stimulated the translocation of Nrf2 from the cytosol to the nucleus and Nrf2 binding to the ARE site in the HO-1 promoter, which could also be inhibited by pretreatment with a PI3K inhibitor, LY294002.",
            "output": [
                "Does macrophage-activating lipopeptide-2 require Mal and PI3K for efficient induction of heme oxygenase-1?"
            ]
        },
        {
            "id": "task847-38c699a5eff0410098f4a0abb981224b",
            "input": "Chronic cytomegalovirus (CMV) infection has been associated with immunosenescence and immunoactivation in the general population. In human immunodeficiency virus type 1 (HIV-1)-infected people, CMV coinfection, in addition to residual HIV replication and microbial translocation, has been proposed as a key factor in sustaining immune activation, even in individuals with a controlled HIV load.', 'Patients from the ICONA Study with at least 1 CMV immunoglobulin G (IgG) test available without active CMV disease were included in the analysis. AIDS-defining event or AIDS-related death and severe non-AIDS-defining event or non-AIDS-related death were taken as clinical progression end points. Independent predictors of CMV were identified by multivariable logistic regression. Probabilities of reaching the end points were estimated by survival analyses.', 'A total of 6111 subjects were included, of whom 5119 (83.3%) were CMV IgG positive at baseline. Patients with CMV IgG positivity at baseline were more likely to develop a severe non-AIDS-defining event/non-AIDS-related death (adjusted hazard ratio [HR], 1.53 [95% confidence interval {CI}, 1.08-2.16]. In particular, CMV seropositivity was an independent risk factor for cardiovascular and cerebrovascular diseases (adjusted HR, 2.27 [95% CI, .97-5.32]).",
            "output": [
                "Is cytomegalovirus coinfection associated with an increased risk of severe non-AIDS-defining events in a large cohort of HIV-infected patients?"
            ]
        },
        {
            "id": "task847-f7110dc811a34971b4e7c470907cf690",
            "input": "Diabetic nephropathy (DN) is a common complication in diabetics. Recent evidence suggests that neutrophil-lymphocyte ratio (NLR) affects the development and acceleration of some diabetic complications. Scholars have rarely investigated the relationship between DN and NLR. This study aims to evaluate the relationship between DN and NLR and estimate whether or not NLR is a reliable marker for early-stage DN.', 'The study included 253 patients with type 2 diabetes mellitus, 115 of whom have early-stage DN. The control group was composed of 210 healthy age- and sex-matched subjects.', 'The NLR values of the patients with diabetes were significantly higher than those of the healthy controls (P < 0\u00b7001), and the NLR values of the patients with early-stage DN were higher than those of the patients without DN (P < 0\u00b7001). Logistic regression analysis showed that the risk predictors of DN include NLR, creatinine, total cholesterol, systolic blood pressure, HbA1c and insulin resistance. NLR (P = 0\u00b7004, EXP(B) = 2\u00b7088, 95% CI = 1\u00b7271-3\u00b7429) levels positively correlated with DN. The DN odds ratio increased by a factor of 2\u00b7088 (95% CI, 1\u00b7271-3\u00b7429) for every one unit increase in NLR.",
            "output": [
                "Is neutrophil-lymphocyte ratio a reliable predictive marker for early-stage diabetic nephropathy?"
            ]
        },
        {
            "id": "task847-dc771428cdf249129dbde0570b5cc705",
            "input": "Mutations in CHD7, a gene previously implicated in CHARGE (coloboma, heart defect, choanal atresia, retardation of growth and/or development, genital hypoplasia, ear anomalies) syndrome, have been reported in patients presenting with Kallmann syndrome (KS) or congenital hypogonadotropic hypogonadism (CHH). Most mutations causing CHARGE syndrome result in premature stop codons and occur de novo, but the proportion of truncating vs nontruncating mutations in KS and CHH patients is still unknown.', 'The objective of the study was to determine the nature, prevalence, mode of transmission, and clinical spectrum of CHD7 mutations in a large series of patients.', 'We studied 209 KS and 94 CHH patients. These patients had not been diagnosed with CHARGE syndrome according to the current criteria. We searched for mutations in 16 KS and CHH genes including CHD7.', 'We found presumably pathogenic mutations in CHD7 in 24 KS patients but not in CHH patients. Nontruncating mutations (16 missense and a two-codon duplication) were more prevalent than truncating mutations (three nonsense, three frame shift, and a splice site), which contrasts with patients presenting with typical CHARGE syndrome. Thus, the clinical spectrum associated with CHD7 mutations may be partly explained by genotype/phenotype correlations. Eight patients also had congenital deafness and one had a cleft lip/palate, whereas six had both. For 10 patients, the presence of diverse features of the CHARGE spectrum in at least one relative argues against a de novo appearance of the missense mutation, and this was confirmed by genetic analysis in five families.",
            "output": [
                "Is the prevalence of CHD7 missense versus truncating mutations higher in patients with Kallmann syndrome than in typical CHARGE patients?"
            ]
        },
        {
            "id": "task847-deb26f52015c4ba1943723a574c07484",
            "input": "An oligonucleotide termed 'T-oligo' having sequence homology with telomere overhang has shown cytotoxicity in multiple cancers. We have demonstrated that T-oligo can induce apoptosis in androgen independent prostate cancer cell line DU-145. In this report, we evaluate the use of star-shaped tetraspermine (SSTS) for delivery of T-oligo.\", 'SSTS was synthesized from spermine and its intrinsic cytotoxicity towards DU-145 cells was compared with spermine and branched polyethyleneimine (bPEI). Atomistic molecular dynamic (MD) simulations were conducted to understand binding and complexation of spermine and SSTS with T-oligo. Complexation was also determined using gel electrophoresis and SYBR gold assay. Complexes were characterized for size, cellular uptake and antiproliferative effect.', 'SSTS exhibited significantly lower toxicity than spermine and bPEI. Its affinity towards T-oligo was significantly higher than spermine as determined by experimental studies and confirmed by MD simulations and it formed stable complexes (TONPs) with T-oligo. TONPs facilitated cellular uptake and nuclear accumulation of T-oligo and their cytotoxic potential was observed at concentration several folds lower than that required for T-oligo alone.",
            "output": [
                "Does star-shaped tetraspermine enhance cellular uptake and cytotoxicity of T-oligo in prostate cancer cells?"
            ]
        },
        {
            "id": "task847-fc0f1472e5a94371b8862602cf7cedb6",
            "input": "To examine the relationship between lexical tone perception and melodic pitch perception in Mandarin-speaking cochlear implant (CI) users and to investigate the influence of previous acoustic hearing on CI users' speech and music perception.\", 'Lexical tone perception and melodic contour identification (MCI) were measured in 21 prelingual and 11 postlingual young (aged 6-26 years) Mandarin-speaking CI users. Lexical tone recognition was measured for four tonal patterns: tone 1 (flat F0), tone 2 (rising F0), tone 3 (falling-rising F0), and tone 4 (falling F0). MCI was measured using nine five-note melodic patterns that contained changes in pitch contour, as well as different semitone spacing between notes.', 'Lexical tone recognition was generally good (overall mean = 81% correct), and there was no significant difference between subject groups. MCI performance was generally poor (mean = 23% correct). MCI performance was significantly better for postlingual (mean = 32% correct) than for prelingual CI participants (mean = 18% correct). After correcting for outliers, there was no significant correlation between lexical tone recognition and MCI performance for prelingual or postlingual CI participants. Age at deafness was significantly correlated with MCI performance only for postlingual participants. CI experience was significantly correlated with MCI performance for both prelingual and postlingual participants. Duration of deafness was significantly correlated with tone recognition only for prelingual participants.",
            "output": [
                "Do melodic pitch perception and lexical tone perception in Mandarin-speaking cochlear implant users?"
            ]
        },
        {
            "id": "task847-6aaedef336bc47988c87a41812e47e9f",
            "input": "Human induced pluripotent stem cells (iPSCs) play an important role in disease modeling and drug testing. However, the current methods are time-consuming and lack an isogenic control.', 'This study sought to establish an efficient technology to generate human PSC-based disease models with isogenic control.', 'The ion channel genes KCNQ1 and KCNH2 with dominant negative mutations causing long QT syndrome types 1 and 2, respectively, were stably integrated into a safe harbor AAVS1 locus using zinc finger nuclease technology.', 'Patch-clamp recording revealed that the edited iPSC-derived cardiomyocytes (iPSC-CMs) displayed characteristic long QT syndrome phenotype and significant prolongation of the action potential duration compared with the unedited control cells. Finally, addition of nifedipine (L-type calcium channel blocker) or pinacidil (KATP-channel opener) shortened the action potential duration of iPSC-CMs, confirming the validity of isogenic iPSC lines for drug testing in the future.",
            "output": [
                "Does genome editing of isogenic human induced pluripotent stem cells recapitulate long QT phenotype for drug testing?"
            ]
        },
        {
            "id": "task847-fb90ee578b1c4ba598ff28bebef7b532",
            "input": "To study the reasons that the seedless fruits of Siraitia grosvenorii developed to smaller ones.', 'The differences of fruit expanding, gene expressing and cell development were investigated between the triploid and diploid fruits from two strains F050 and F049.', 'The results showed the expanding of triploid fruits was stopped about 20 days after artificial pollination, 10 days earlier than the diploid fruits. Meanwhile, it was also investigated that aux expressing level in the triploid fruits was greatly higher than that in diploid fruits, while its ipt, cyt-p450, spds, cycB, cycD1, cycD3, cdkA, cdkB, exp and xth expressing level were greatly lower than that in diploid fruits. The majority of sarcocarp cells of the triploid fruits kept in the stage of small ones comparing with the diploid fruits.",
            "output": [
                "Do [ Reasons that seedless fruits of Siraitia grosvenorii become small ]?"
            ]
        },
        {
            "id": "task847-439701e1be5c4118a41076bb981595fe",
            "input": "A computerized physician order entry (CPOE) system with embedded clinical decision support can reduce medication errors in hospitals, but might increase the time taken to generate orders.', 'We aimed to quantify the effects of temporal (month, day of week, hour of shift) and other factors (grade of doctor, prior experience with the system, alert characteristics, and shift type) on the time taken to generate a prescription order.', 'A large university teaching hospital using a locally developed CPOE system with an extensive audit database.', 'We retrospectively analyzed prescription orders from the audit database between August 2011 and July 2012.', 'The geometric mean time taken to generate a prescription order within the CPOE system was 11.75\\u2005s (95% CI 11.72 to 11.78). Time to prescribe was most affected by the display of high-level (24.59\\u2005s (24.43 to 24.76); p<0.001) or previously unseen (18.87\\u2005s (18.78 to 18.96); p<0.001) alerts. Prescribers took significantly less time at weekends (11.29\\u2005s (11.23 to 11.35)) than on weekdays (11.88\\u2005s (11.84 to 11.91); p<0.001), in the first (11.25\\u2005s (11.16 to 11.34); p<0.001) and final (11.56\\u2005s (11.47 to 11.66); p<0.001) hour of their shifts, and after the first month of using the system.",
            "output": [
                "Do temporal and other factors that influence the time doctors take to prescribe using an electronic prescribing system?"
            ]
        },
        {
            "id": "task847-6980ad68dff7438286dfcde372a574fb",
            "input": "Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it is still lacking effective prognostic biomarkers so far. Previous results of the iTRAQ-based quantitative proteomics study (iTRAQ-2DLC-MS/MS) have shown that \u03b1-methylacyl-CoA racemase (AMACR) might be a promising prognostic biomarker for the early recurrence/metastasis of hepatocellular carcinoma (HCC). Here a large-scale cohort clinical study was performed to evaluate its prognostic potential.', 'HCC samples from patients (n=158) were used for the construction of tissue microarray. The expression level of AMACR was determined by immunohistochemical staining. A large-scale cohort clinical study between the expression of AMACR and some major clinical parameter has been performed to assess the prognostic potential of AMACR for the early recurrence/metastasis of HCC.', 'Some important clinical parameters such as \u03b1-fetoprotein, tumour numbers, dissemination to regional lymph nodes, tumour capsule and portal vein tumour thrombosis are significantly associated with the low expression of AMACR. The expression of AMACR was an independent factor for the survival of patients with HCC. The median survival time was 17 months in the low-expression group compared with 45 months in the high-expression group.",
            "output": [
                "Does \u03b1-Methylacyl-CoA racemase ( AMACR ) serve as a prognostic biomarker for the early recurrence/metastasis of HCC?"
            ]
        },
        {
            "id": "task847-1c49cb3908934c4ab3902634cff8b3ea",
            "input": "To evaluate the immediate effects of indirect moxibustion, a traditional local thermal therapy, on renal hemodynamics by using Doppler ultrasonography (US).', 'Prospective observational study of postintervention changes in several variables.', 'Gifu University Hospital, Gifu, Japan.', 'Eleven healthy persons (7 men and 4 women; mean age\u00b1standard deviation, 32.6\u00b15.7 years) were enrolled.', 'Indirect moxibustion was applied for 4 minutes to bilateral lower back acupuncture points (BL23). Each participant received 3 successive treatments.', 'The main outcome measurement was resistive index (RI) in the renal segmental arteries. Blood flow variables, including RI, were measured for 6 renal segmental arteries by Doppler US at rest (baseline), immediately after completion of moxibustion (post 1), and 10 minutes later (post 2). Participants were monitored for adverse events during the intervention.', 'The mean RI was 0.578\u00b10.037 at baseline, 0.546\u00b10.027 at post 1, and 0.547\u00b10.032 at post 2. RI decreased significantly between post 1 and baseline (95% confidence interval [CI], -0.053 to -0.011; p=0.003) and between post 2 and baseline (95% CI, -0.052 to -0.009; p=0.005). No adverse events, such as burns, were observed.",
            "output": [
                "Does traditional thermal therapy with indirect moxibustion decrease renal arterial resistive index?"
            ]
        },
        {
            "id": "task847-2bb87c3c59cb4be5b3a2161c3724a4f6",
            "input": "Korean red ginseng (ginseng, Panax ginseng C.A. Meyer) has traditionally been used in the treatment of most ageing-related diseases, such as obesity, diabetes, and dyslipidemia, but the mechanism of the effects is unclear. The aim of this study was to determine the effects of ginseng on obesity in a mouse model of female obesity (obese female db/db mouse) and to investigate the mechanism of anti-obesity effects.', 'After female db/db (B6.Cg-m Lepr(db)/++/J) mice were treated with 5% (w/w) ginseng for 13 weeks, variables and parameters of obesity and disorders related to obesity were examined. Blood vessel density and the expression of genes involved in angiogenesis were also measured.', 'Mice treated with ginseng for 13 weeks had less body weight and lower adipose tissue mass compared to control, untreated mice. The size of adipocytes was smaller in visceral adipose tissues of ginseng-treated mice. Obesity-related complications, such as hepatic steatosis, hypertriglyceridemia, and hyperglycemia, were markedly improved in treated mice. Blood vessel density was lower in visceral adipose tissue sections from treated mice than those from control mice. Concomitantly, mRNA levels for VEGF-A and FGF-2 were lower in both visceral adipose tissue from treated mice and treated 3T3-L1 cells compared to those from untreated controls. Protein levels for VEGF were also lower in visceral adipose tissue from treated mice. In contrast, ginseng increased mRNA expression of genes responsible for energy expenditure and fatty acid \u03b2-oxidation in visceral adipose tissue during ginseng-induced weight reduction.",
            "output": [
                "Does ginseng treatment reverse obesity and related disorders by inhibiting angiogenesis in female db/db mice?"
            ]
        },
        {
            "id": "task847-4249be03e54f4bbeac6c2bcd1e5fc12b",
            "input": "We have described cerebrospinal fluid (CSF) myeloid microvesicles (MVs) as a marker of microglia activation during neuroinflammation in Alzheimer disease (AD), and characterized their ability to produce toxic amyloid \u03b21-42 (A\u03b21-42 ) oligomers from aggregated or soluble substrate. The aim of this study is to investigate the association of CSF myeloid MVs with neuroimaging, clinical, and paraclinical data in AD and mild cognitive impairment (MCI).', 'We collected CSF from 106 AD patients, 51 MCI patients, and 29 neurologically healthy controls. We examined CSF myeloid MV content and AD markers. A subgroup of 34 AD and 21 MCI patients underwent structural and diffusion tensor MRI.', 'Higher levels of myeloid MVs were found in the CSF of AD patients and MCI patients converting within 3 years relative to controls, but also, at a lower level, in MCI patients not converting to AD. CSF myeloid MVs were associated with Tau but not with A\u03b21-42 CSF levels. CSF MVs levels correlated with white matter (WM) tract damage in MCI, and with hippocampal atrophy in AD.",
            "output": [
                "Are myeloid microvesicles in cerebrospinal fluid associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease?"
            ]
        },
        {
            "id": "task847-2df20ecf157d464095f5e592ba610502",
            "input": "Surgical debridement is often required to treat spinal infections. Successful surgery requires accurate localization of the active infections, however, current imaging technique still requires surgeons' experience to narrow the surgical fields to achieve less invasive procedures.\", 'To investigate the use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for successful surgical planning.', 'Nine patients with suspected spinal infection underwent magnetic resonance imaging (MRI) and FDG-PET/CT before surgery to locate active foci of infections. The spinal structures were divided into seven compartments at each intervertebral disc level for a total of 315 compartments investigated. The same classification system was used to design operating fields for histological correlation.', 'FDG-PET/CT diagnosed fewer compartments as active infection (34 compartments, 10.8%) than MRI (62 compartments, 19.7%, P\\u2009\\u2009=\\u20090.002). Surgical exploration was performed in 49 compartments, and demonstrated active infection in 25 compartments. The sensitivity / specificity of FDG-PET/CT was 100% / 79%, respectively, which was superior to those of MRI, 76% / 42%. Foci of active infection showed hypermetabolic activity with a SUVmax of 7.1\\u2009\u00b1\\u20092.6 (range, 3.0-12.7). Receiver operating characteristic (ROC) analysis indicated an optimal threshold for active spinal infection at a SUVmax of 4.2, corresponding to a sensitivity of 90.3% and specificity of 91.2%.",
            "output": [
                "Does 18F-FDG-PET/CT better localize active spinal infection than MRI for successful minimally invasive surgery?"
            ]
        },
        {
            "id": "task847-3aef19b1c7b14fa28a0ea3edd8936270",
            "input": "MicroRNA-222 (miR-222) has been shown to play a potential oncogenic role in bladder cancer. The aim of this study was to evaluate the expression of miR-222 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival.', 'Surgical specimens of cancer tissue and adjacent normal tissue were obtained from 97 patients with bladder cancer. The relative expression levels of miR-222 in the cancer and the normal adjacent tissue were measured by quantitative reverse-transcriptase PCR. We analyzed their correlation with clinicopathological parameters and prognostic value.', 'The expression level of miR-222 was significantly higher in tumor tissues than in corresponding non-cancerous tissues (5.46\\u2009\u00b1\\u20091.45 versus 1.92\\u2009\u00b1\\u20090.65, P\\u2009< \\u20090.0001), and a high expression of miR-222 was found to be significantly associated with tumor grade (P\\u2009=\\u20090.003) and tumor stage (P\\u2009=\\u20090.005). The miR-222 expression level was classified as high or low in relation to the median value (cutoff value\\u2009=\\u20095.15). Kaplan-Meier analysis showed that patients with higher levels of miR-222 had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year overall survival of 29.53% and 52.75%, respectively (P\\u2009=\\u20090.0034). In the multivariate Cox proportional hazards analysis, which included miR-222 level, tumor grade, tumor stage, and tumor number, high miR-222 expression was independently associated with poor survival (P\\u2009<\\u20090.001; hazard ratio 6.17; 95% CI 2.33 to 10.39).",
            "output": [
                "Is increased expression of miR-222 associated with poor prognosis in bladder cancer?"
            ]
        },
        {
            "id": "task847-2c21df6c1c354359a94ac592770f2f3b",
            "input": "The integrity and evolution of lichen symbioses depend on a fine-tuned combination of algal and fungal genotypes. Geographically widespread species complexes of lichenized fungi can occur in habitats with slightly varying ecological conditions, and it remains unclear how this variation correlates with symbiont selectivity patterns in lichens. In an attempt to address this question, >300 samples were taken of the globally distributed and ecologically variable lichen-forming species complex Tephromela atra, together with closely allied species, in order to study genetic diversity and the selectivity patterns of their photobionts.', 'Lichen thalli of T. atra and of closely related species T. grumosa, T. nashii and T. atrocaesia were collected from six continents, across 24 countries and 62 localities representing a wide range of habitats. Analyses of genetic diversity and phylogenetic relationships were carried out both for photobionts amplified directly from the lichen thalli and from those isolated in axenic cultures. Morphological and anatomical traits were studied with light and transmission electron microscopy in the isolated algal strains.', 'Tephromela fungal species were found to associate with 12 lineages of Trebouxia. Five new clades demonstrate the still-unrecognized genetic diversity of lichen algae. Culturable, undescribed lineages were also characterized by phenotypic traits. Strong selectivity of the mycobionts for the photobionts was observed in six monophyletic Tephromela clades. Seven Trebouxia lineages were detected in the poorly resolved lineage T. atra sensu lato, where co-occurrence of multiple photobiont lineages in single thalli was repeatedly observed.",
            "output": [
                "Does photobiont selectivity lead to ecological tolerance and evolutionary divergence in a polymorphic complex of lichenized fungi?"
            ]
        },
        {
            "id": "task847-7fe5896b886a4efb86fac8e615dc7121",
            "input": "Left ventricular (LV) torsion is an important parameter of LV performance and can be influenced by several factors. Aim of this investigation was to evaluate whether QRS prolongation in left bundle branch block (LBBB) may influence global LV twist and twisting/untwisting rate in chronic systolic heart failure (HF) patients.', \"We prospectively evaluated 30 healthy subjects (control group) and 100 chronic HF patients with severely impaired LV systolic function (ejection fraction \u2264 35%). Patients were divided into three groups according to QRS duration: A: QRS < 120 ms (n 49), B: 120 \u2264 QRS \u2264 150 ms (n 28) and C: QRS > 150 ms (n 23). Patients in groups B and C presented LBBB. All subjects underwent standard trans-thoracic echocardiography and two-dimensional speckle-tracking echocardiography evaluation. Categorical variables were compared by the chi-square or the Fisher's exact test. Continuous variables were compared using the ANOVA test. Correlations between variables were analysed with linear regression.\", 'Control subjects presented higher torsion parameters, when compared with patients in any HF group. Among the three HF groups, no differences were detected in global twist (4.79 \u00b1 3.54, 3.8 \u00b1 3.0 and 4.15 \u00b1 3.14 degrees, respectively), twist rate max (44.81 \u00b1 25.03, 37.94 \u00b1 19.09 and 37.61 \u00b1 24.49 degrees s(-1), respectively) and untwist rate max (-36.31 \u00b1 30.89, -27.68 \u00b1 34.67 and -39.62 \u00b1 26.27 degrees s(-1), respectively) (P>0.05 for all). At linear regression analysis, there was no relation between QRS duration and any torsion parameter (P>0.05 for all).",
            "output": [
                "Does qRS duration in left bundle branch block affect left ventricular twisting in chronic systolic heart failure?"
            ]
        },
        {
            "id": "task847-bea7795f46a140b09ad76dbc71ce4cc9",
            "input": "The appropriate management of patients with mitral regurgitation (MR) and left ventricular dysfunction (LVD) is controversial. The study aim was to determine whether the presence of contractile reserve (CR) assessed by dobutamine stress echocardiography (DSE) was associated with improved outcomes.', 'Death and heart transplantation were analyzed as the primary outcomes associated with the presence of CR. A total of 125 consecutive patients (96 males, 29 females; mean age 60 +/- 12 years) with left ventricular ejection fraction (LVEF) < or = 35% and hemodynamically significant MR underwent DSE between 1999 and 2005. CR was defined as an increase in LVEF of > or = 10% during dobutamine infusion.', 'Among 125 patients, 55 (43.0%) showed evidence of CR. Within five years after DSE, 24 patients (34.3%) in the CR- group and seven (12.7%) in the CR+ group had died or required heart transplantation (p < 0.01, log rank). After adjusting for age, baseline LVEF, NYHA class and moderate/severe tricuspid regurgitation (TR), CR remained an independent predictor of time to death or heart transplantation (HR 0.34; 95% CI: 0.15-0.76, p < 0.01). Improvement in the degree of MR was present at one year in 85.0% of CR+ patients, and in 62.5% of CR- patients (p = 0.03). An improvement of 5% in LVEF was noted in the CR+ group, compared to 0% in the CR- group (p = 0.04).",
            "output": [
                "Does contractile reserve induced with dobutamine echocardiography predict outcome in patients with left ventricular dysfunction and mitral regurgitation?"
            ]
        },
        {
            "id": "task847-ef5a68d307b447b7b0a065aff537c327",
            "input": "Telomerase, a ribonucleoprotein enzyme mainly consisted of a catalytic protein subunit human telomerase reverse transcriptase (hTERT) and a human telomerase RNA component, is responsible for maintaining telomeres. Telomerase over-expression correlates significantly with tumors and is a prognostic marker. However, telomerase over-expression in breast cancers and the effect of telomerase inhibition as a candidate cancer therapy are unknown.', 'We used the dominant-negative mutant of hTERT (DN-hTERT) to inhibit telomerase activity on human breast adenocarcinoma cell line MCF-7 by transfection. Telomeric repeat amplification protocol assays and real-time quantitative RT-PCR were performed to investigate telomerase activity as well as expression of hTERT. Telomere length was measured by the flow-fluorescence in situ hybridization assay. Cell proliferation was assessed by the WST-8 assay, and apoptosis was evaluated by flow cytometry. The tumor formation ability of MCF-7 cells was investigated by transplanting cells subcutaneously into BALB/c nude mice.', 'Ectopic expression of DN-hTERT caused dramatically inhibition of telomerase activity and reduction of telomere length. Telomerase inhibition induced growth arrest and apoptosis of MCF7 cells in vitro and loss of tumorigenic properties in vivo.",
            "output": [
                "Does inhibition of telomerase activity by dominant-negative hTERT retard the growth of breast cancer cells?"
            ]
        },
        {
            "id": "task847-034e43dc6fb44226ae7332bb1858f7b1",
            "input": "Management of cardiac surgery patients is a very standardized procedure in respective local institutions. Yet only very limited evidence exists concerning optimal indication, safety and efficacy of hemodynamic monitoring catecholamine and fluid therapy.', 'Between April and May 2013, all 81 German anaesthesia departments involved in cardiac surgery care were asked to participate in a questionnaire addressing the institutional specific current practice in hemodynamic monitoring, catecholamine and volume therapy.', '51 (63%) questionnaires were completed and returned. All participating centers used basic hemodynamic monitoring (i.e. invasive arterial blood pressure and central venous pressure), supplemented by transesophageal echocardiography. Pulmonary arterial catheter and calibrated trend monitoring devices were also routinely available. In contrast, non-calibrated trend monitoring and esophageal doppler ultrasound devices were not commonly in use. Cerebral oximetry is increasingly emerging, but lacks clear indications. The majority of patients undergoing cardiac surgery, especially in university hospitals, required catecholamines during perioperative care, In case of low cardiac output syndrome, dobutamine (32%), epinephrine (30%) or phosphodiesterase inhibitors (8%) were first choice. In case of hypotension following vasoplegia, norepinephrine (96%) represented the most common catecholamine. 88% of the participating centers reported regular use of colloid fluids, with hydroxyethyl starches (HES) being first choice (64%).",
            "output": [
                "Does catecholamine and volume therapy for cardiac surgery in Germany -- result from a postal survey?"
            ]
        },
        {
            "id": "task847-f5d8fd801ac045a2bcff011107ae57ba",
            "input": "Low energy shock waves have been shown to induce angiogenesis, improve left ventricular ejection fraction and decrease angina symptoms in patients suffering from chronic ischemic heart disease. Whether there is as well an effect in acute ischemia was not yet investigated.', 'Hind-limb ischemia was induced in 10-12 weeks old male C57/Bl6 wild-type mice by excision of the left femoral artery. Animals were randomly divided in a treatment group (SWT, 300 shock waves at 0.1 mJ/mm2, 5 Hz) and untreated controls (CTR), n = 10 per group. The treatment group received shock wave therapy immediately after surgery.', 'Higher gene expression and protein levels of angiogenic factors VEGF-A and PlGF, as well as their receptors Flt-1 and KDR have been found. This resulted in significantly more vessels per high-power field in SWT compared to controls. Improvement of blood perfusion in treatment animals was confirmed by laser Doppler perfusion imaging. Receptor tyrosine kinase profiler revealed significant phosphorylation of VEGF receptor 2 as an underlying mechanism of action. The effect of VEGF signaling was abolished upon incubation with a VEGFR2 inhibitor indicating that the effect is indeed VEGFR 2 dependent.",
            "output": [
                "Does low energy shock wave therapy induce angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation?"
            ]
        },
        {
            "id": "task847-819dedc2a610466588ffa3c5ebdcfb87",
            "input": "Accurate evaluation of the biological behavior of Gastrointestinal stromal tumor and careful selection of patients with a high risk for tumor recurrence are necessary. In the present study, we analyzed prognostic factors in patients with GIST.', 'A total of 214 patients who had undergone curative resection of a localized primary gastric GIST without adjuvant therapy were enrolled in this retrospective study. Prognostic factors were analyzed. The growth pattern was classified as intramural, endoluminal, exoluminal, or mixed- type.', 'On univariate and multivariate analyses, recurrence was predicted by exoluminal or mixed-type (hazard ratio [HR]=3.7, p=0.043), tumor size of >3.5 cm (HR=7.1, p=0.01), and mitotic rate of >5/50 high-power fields (HR=7.9, p<0.001).",
            "output": [
                "Is macroscopic type a prognostic factor for recurrence-free survival after resection of gastric GIST?"
            ]
        },
        {
            "id": "task847-8799ae4eb6e0432390c83e835030d440",
            "input": "To assess the identification accuracy of dynamic assessment (DA) of narrative ability in English for children learning English as a 2nd language.', 'A DA task was administered to 54 children: 18 Spanish-English-speaking children with language impairment (LI); 18 age-, sex-, IQ- and language experience-matched typical control children; and an additional 18 age- and language experience-matched comparison children. A variety of quantitative and qualitative measures were collected in the pretest phase, the mediation phase, and the posttest phase of the study. Exploratory discriminant analysis was used to determine the set of measures that best differentiated among this group of children with and without LI.', 'A combination of examiner ratings of modifiability (compliance, metacognition, and task orientation), DA story scores (setting, dialogue, and complexity of vocabulary), and ungrammaticality (derived from the posttest narrative sample) classified children with 80.6% to 97.2% accuracy.",
            "output": [
                "Does dynamic assessment of narrative ability in English accurately identify language impairment in English language learners?"
            ]
        },
        {
            "id": "task847-f2f132be8dea4055a8edc3d3539c6214",
            "input": "To develop a scale and survey the measurement of patient adherence and patient recruitment, and to explore how these methods impact the results in randomized controlled trials of interventions to improve patient adherence to medications.', 'Analytic survey of a purposively selected sample of patient adherence intervention trials from a systematic review, assessing the quality of adherence measurement and patient recruitment methods.', 'We identified 44 different measures of adherence, with qualities ranging from valid and objective to unreliable and subjective. The median overall quality of measures of adherence was 5 (interquartile range [IQR], 3; range, 0-9, 9 is high quality). The quality of the measures was associated with variation in the estimate of adherence (Spearman r\\xa0=\\xa00.66; 95% confidence interval: 0.39, 0.83). The median overall quality of patient recruitment methods was 2 (IQR, 1; maximum score 6, higher is better). There was no significant correlation between the power of the trial to detect an effect and the quality of the patient recruitment methods.",
            "output": [
                "Are adherence measurement and patient recruitment methods poor in intervention trials to improve patient adherence?"
            ]
        },
        {
            "id": "task847-0a9a3d8dab974d68b053015fda751a52",
            "input": "Spontaneous bacterial peritonitis (SBP) is associated with high mortality. Early paracentesis (EP) is essential for rapid diagnosis and optimal treatment. The aim of the study is to compare the outcomes of patients with SBP who received EP vs. delayed paracentesis (DP).', 'Consecutive patients who were diagnosed with SBP (ascites neutrophil count \u2265250 cells/mm(3) and clinical evidence of cirrhosis) <72\\u2009h from the first physician encounter at two centers were identified. EP was defined by receiving paracentesis <12\\u2009h and DP 12-72\\u2009h from hospitalization. Primary outcome was in-hospital mortality.', 'The mean age of 239 patients with SBP was 53\u00b110 years; mean Model for End-Stage Liver Disease (MELD) score was 22\u00b19. In all, 98 (41%) patients who received DP had a higher in-hospital mortality (27% vs. 13%, P=0.007) compared with 141 (59%) who received EP. Furthermore, DP group had longer intensive care days (4.0\u00b19.5 vs. 1.3\u00b14.1, P=0.008), hospital days (13.0\u00b114.7 vs. 8.4\u00b17.4, P=0.005), and higher 3-month mortality (28/76, 37% vs. 21/98, 21%; P=0.03) compared with the EP group. Adjusting for MELD score \u226522 (adjusted odds ratio (AOR)=5.7, 95% confidence interval (CI)=1.8-18.5) and creatinine levels \u22651.5\\u2009mg/dl (AOR=3.2, 95% CI=1.4-7.2), DP was associated with increased in-hospital mortality (AOR=2.7, 95% CI=1.3-4.8). Each hour delay in paracentesis was associated with a 3.3% (95% CI=1.3-5.4%) increase in in-hospital mortality after adjusting for MELD score and creatinine levels.",
            "output": [
                "Is delayed paracentesis associated with increased in-hospital mortality in patients with spontaneous bacterial peritonitis?"
            ]
        },
        {
            "id": "task847-23a4ba6624714441ad16a682c073d30c",
            "input": "The aim of this study was to demonstrate the effect of low-level light therapy (LLLT) in an acute colitis model in mice.', 'Low-level light therapy (LLLT) has been shown to be an effective treatment for various inflammatory processes such as oral mucositis and diabetic foot ulcers.', 'Colitis was induced by dextran sodium sulfate (DSS) in mice in four blinded controlled studies (validation of model, efficacy study, and two studies for evaluation of optimal dose). LLLT was applied to the colon utilizing a small diameter endoscope with an LED-based light source in several wavelengths (440, 660, and 850\\u2009nm at 1\\u2009J/cm(2)) and then 850\\u2009nm at several doses (1, 0.5, 0.25, and 0.1\\u2009J/cm(2)). LLLT was initiated 1 day prior to induction of colitis and went on for the 6 day induction period as well as for the following 3-10 days. Dose was controlled by changing exposure time. Disease activity was scored endoscopically and by histopathological assessment.', 'Statistically significant improvement in disease severity was observed in the treatment groups compared with the control groups. The three wavelengths used demonstrated efficacy, and a clear dose-response curve was observed for one of the wavelengths (850\\u2009nm). On day 11, colonoscopic scoring in the sham-treated mice increased from 7.9\u00b11.3 to 12.2\u00b12.2, while activity in all treated groups remained stable.",
            "output": [
                "Does low-level light therapy induce mucosal healing in a murine model of dextran-sodium-sulfate induced colitis?"
            ]
        },
        {
            "id": "task847-e39c6ca39c1e4da09f2a66d224c49c7e",
            "input": "Toker cells are clear cells present in the squamous epithelium of the nipple of some women. In contrast to squamous epithelium, they are cytokeratin 7 (CK7) positive. The origin of these cells is not completely understood. It has been suggested that they may represent abortive glands or migratory ductal cells; and may be precursors of Paget's disease of the nipple. Our aim was to investigate the incidence and distribution of Toker cells and their relationship with lactiferous ducts.\", 'We examined nipple sections from 100 consecutive mastectomies performed at Charing Cross hospital. New sections were stained for CK7 using the immunoperoxidase technique.', \"Toker cells were identified in 11 cases. They were always clustered within the squamous epithelium superficial to sebaceous glands with no relationship with lactiferous ducts. Two cases in the study had Paget's disease and these were not associated with underlying sebaceous glands.",
            "output": [
                "Are toker cells of the nipple commonly associated with underlying sebaceous glands but not with lactiferous ducts?"
            ]
        },
        {
            "id": "task847-6a3e67168725419b80f76e5576b9c453",
            "input": "Involved field radiotherapy (IFRT) after cytotoxic chemotherapy has become the standard of care in treating pediatric patients with Hodgkin lymphoma. However, recent interest in shrinking the treatment volume to involved node radiotherapy (INRT) may allow lower doses to critical organ structures. We dosimetrically compared IFRT and INRT treatment approaches.', 'INRT treatment plans were retrospectively constructed from 17 consecutively treated pediatric patients identified with Hodgkin lymphoma who had been previously treated with conventional IFRT. The radiation doses delivered to organs-at-risk (OARs) with virtual INRT treatment plans based on INRT field design were then compared to the original IFRT treatment plans. Metrics for comparison included mean doses to organs and volumes of organ receiving at least 50% of the original prescription dose (V50%). A one-tailed, paired t-test was then performed to verify statistical significance at an alpha level of 0.05.', 'All organs at risk compared in this investigation (kidneys, heart, thyroid, parotids, and lungs) had significantly lower doses of radiation with INRT when compared to IFRT (p<0.05). Furthermore, the volume of the breast receiving at least 50% of the initial prescription dose was statistically lower in the INRT plans.",
            "output": [
                "Does involved-nodal radiation therapy lead to lower doses to critical organs-at-risk compared to involved-field radiation therapy?"
            ]
        },
        {
            "id": "task847-d21910cf5cb74c00bb05f3e571376df3",
            "input": "Ibulocydine (IB), a novel prodrug of CDK inhibitor, has been reported to have anti-cancer effect in human hepatoma cells. In order to address its feasibility as a radiosensitizer to improve radiotherapeutic efficacy for human cancers, this study was designed.', 'Human cancer cells of lung and colon were treated with IB and/or radiotherapy (RT). The cellular effects were assessed by CCK-8, clonogenic, flow cytometric, and western blotting assays. In vivo radiotherapeutic efficacy was evaluated using the xenograft mouse model.', 'Combined treatment of IB and RT significantly reduced viability and survival fraction of the cells. Apoptotic cell death accompanied with activation of caspases, decrease in Bcl-2/Bax expression, loss of mitochondrial membrane potential (MMP) leading to release of cytochrome c into cytosol was observed. Recovery of Bcl-2 expression level by introducing Bcl-2 expressing plasmid DNA compromised the loss of MMP and apoptosis induced by IB and RT. In vivo therapeutic efficacy of combined treatment was verified in the xenograft mouse model, in which tumor growth was markedly delayed by RT with IB.",
            "output": [
                "Does ibulocydine sensitize human cancers to radiotherapy by induction of mitochondria-mediated apoptosis?"
            ]
        },
        {
            "id": "task847-e4ca6c136cf44a73bdd4f0a5e7a571be",
            "input": "Total hip replacement (THR) outcomes have been worse for patients with rheumatoid arthritis (RA) compared with those who have osteoarthritis (OA). Whether this remains true in contemporary patients with RA with a high use of disease-modifying and biologic therapy is unknown. The purpose of our study is to assess pain, function, and quality of life 2 years after primary THR, comparing patients with RA and patients with OA.', 'Baseline and 2-year data were compared between validated patients with RA and patients with OA who were enrolled in a single-center THR registry between May 1, 2007, and February 25, 2011.', 'There were 5666 eligible primary THR identified, of which 193 were for RA. RA THR had worse baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (44.8 vs 53.2, p < 0.001) and function (38.7 vs 49.9, p < 0.001) compared with OA. These differences remained after surgery: pain (88.4 vs 94.0, p < 0.001) and function (82.9 vs 91.8, p < 0.001). Patients with RA were as likely to have a significant improvement as patients with OA (\u0394 WOMAC > 10) in pain (94% vs 96%, p = 0.35) and function (95% vs 94%, p = 0.69), but were 4 times as likely to have worse function (WOMAC \u2264 60; 19% vs 4%, p < 0.001) and pain (12% vs 3%, p < 0.001). In multivariate logistic regression controlling for multiple potential confounders, RA increased the odds of poor postoperative function (OR 4.32, 95% CI 1.57-11.9), and in patients without a previous primary THR, worse postoperative pain (OR 3.17, 95% CI 1.06-9.53).",
            "output": [
                "Are patients with rheumatoid arthritis more likely to have pain and poor function after total hip replacements than patients with osteoarthritis?"
            ]
        },
        {
            "id": "task847-fea01f54f7a24b35ba42f87d2003fec3",
            "input": "To investigate whether use of adalimumab decreases the frequency of attacks of anterior uveitis (AU) in patients with ankylosing spondylitis (AS).', 'Consecutive patients with AS, visiting an outpatient clinic and treated for at least 12 weeks with adalimumab, were enrolled. The number of attacks of AU in the year before start and during treatment were assessed by patient history and ophthalmological controls.', 'In the 77 patients a total of 52 AU attacks occurred in the year before baseline (68 attacks per 100 patient-yrs), whereas during adalimumab treatment 19 attacks were seen (14 per 100 patient-yrs; reduction rate 80%). Twenty-six patients with AU in the year before start of adalimumab treatment had recurrent attacks, with a median number of 2.0 AU attacks per year [interquartile range (IQR) 1.00-3.00], whereas during treatment this decreased to 10 patients with a median number of 0.56 attacks per year (IQR 0.30-0.75). Hence, the number of attacks per year decreased by 72% (p = 0.000).",
            "output": [
                "Does adalimumab significantly reduce the recurrence rate of anterior uveitis in patients with ankylosing spondylitis?"
            ]
        },
        {
            "id": "task847-8003056d341f4eafb116d48aa055a889",
            "input": "Interleukin 22 (IL-22) plays an important role in the promotion of antimicrobial immunity. However, dysregulated IL-22 action leads to inflammation and is involved in autoimmune diseases, including systemic lupus erythematosus (SLE). IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We investigated the expression and potential significance of serum and urinary IL-22BP levels in patients with SLE.', 'A total of 112 patients with SLE and healthy control subjects participated in our study. Patients were classified according to kidney involvement and disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, complement factor 3 (C3), C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The concentrations of IL-22BP and IL-22 were measured by ELISA. The expression of IL-22BP in the renal tissue was detected by immunohistochemistry.', 'Patients with active renal disease had urinary levels of IL-22BP higher than (1) patients with active SLE but no renal involvement, (2) patients with a history of lupus nephritis in remission with no systemic disease activity and no history of renal involvement, and (3) control subjects. There was no difference in serum levels of IL-22BP among the groups. Urinary levels of IL-22BP in patients with active renal disease were positively correlated with SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics renal activity score, and histological activity index. IL-22BP was highly expressed in renal tissue of patients with active renal disease. After 6 months of treatment, urinary IL-22BP levels decreased significantly in patients with complete response, but remained unchanged in those with partial or no response.",
            "output": [
                "Do increased urinary interleukin 22 binding protein levels correlate with lupus nephritis activity?"
            ]
        },
        {
            "id": "task847-1030ad9f3c4540af8060f2bda9695189",
            "input": "Statins have been shown to possess antiinflammatory and immunomodulatory effects. In this study, we sought to determine if preoperative statin therapy is associated with a reduced frequency of postoperative acute respiratory distress syndrome (ARDS) in surgical populations at increased risk of developing ARDS.', 'We performed a retrospective cohort evaluation of the association between preoperative statin therapy and early postoperative ARDS in patients undergoing elective high-risk thoracic and aortic vascular surgery. The association between preoperative statin therapy and postoperative ARDS was assessed using propensity-adjusted analyses to control for indication bias and confounding factors.', 'Of 1845 patients, 722 were receiving preoperative statin therapy. One hundred twenty patients developed postoperative ARDS. Frequencies of ARDS among those receiving statin therapy versus those who were not was 7.2% and 6.1%, respectively (OR = 1.20; 95% CI, 0.83-1.75; P = 0.330). Neither the stratified propensity score analysis (pooled OR 0.93; 95% CI, 0.60-1.43) nor matched analysis (OR = 0.78; 95% CI, 0.48-1.27) identified a statistically significant association between preoperative statin administration and postoperative ARDS. When compared to matched controls, patients who developed postoperative ARDS did not differ in mortality (7.7% vs 8.8%, P = 0.51), hospital length of stay (21 days vs 15 days, P = 0.21), or ventilator-free days (24 days vs 25 days, P = 0.62).",
            "output": [
                "Does preoperative statin administration protect against early postoperative acute respiratory distress syndrome : a retrospective cohort study?"
            ]
        },
        {
            "id": "task847-e145fd62e5794f3fbc8e7d77091b87d2",
            "input": "In multiple sclerosis (MS), cerebral gray matter (GM) atrophy correlates more strongly than white matter (WM) atrophy with disability. The corresponding relationships in the spinal cord (SC) are unknown due to technical limitations in assessing SC GM atrophy. Using phase-sensitive inversion recovery (PSIR) magnetic resonance imaging, we determined the association of the SC GM and SC WM areas with MS disability and disease type.', 'A total of 113 MS patients and 20 healthy controls were examined at 3T with a PSIR sequence acquired at the C2/C3 disk level. Two independent, clinically masked readers measured the cord WM and GM areas. Correlations between cord areas and Expanded Disability Status Score (EDSS) were determined. Differences in areas between groups were assessed with age and sex as covariates.', 'Relapsing MS (RMS) patients showed smaller SC GM areas than age- and sex-matched controls (p = 0.008) without significant differences in SC WM areas. Progressive MS patients showed smaller SC GM and SC WM areas compared to RMS patients (all p \u2264 0.004). SC GM, SC WM, and whole cord areas inversely correlated with EDSS (rho: -0.60, -0.32, -0.42, respectively; all p \u2264 0.001). The SC GM area was the strongest correlate of disability in multivariate models including brain GM and WM volumes, fluid-attenuated inversion recovery lesion load, T1 lesion load, SC WM area, number of SC T2 lesions, age, sex, and disease duration. Brain and spinal GM independently contributed to EDSS.",
            "output": [
                "Does spinal cord gray matter atrophy correlate with multiple sclerosis disability?"
            ]
        },
        {
            "id": "task847-3f98144e9743457b9b543232c1286598",
            "input": "In the presence of comorbidities the effectiveness of many cardioprotective strategies is blunted. The goal of this study was to assess in a hypertensive rat model if the early reperfusion with anti-hypertensive and pro-angiogenic Chromogranin A-derived peptide, Catestatin (CST:hCgA352-372; CST-Post), protects the heart via Reperfusion-Injury-Salvage-Kinases (RISK)-pathway activation, limiting infarct-size and apoptosis, and promoting angiogenetic factors (e.g., hypoxia inducible factor, HIF-1\u03b1, and endothelial nitric oxide synthase, eNOS, expression).', 'The effects of CST-Post on infarct-size, apoptosis and pro-angiogenetic factors were studied in isolated hearts of spontaneously hypertensive rats (SHR), which underwent the following protocols: (a) 30-min ischemia and 120-min reperfusion (I/R); (b) 30-min ischemia and 20-min reperfusion (I/R-short), both with and without CST-Post (75 nM for 20-min at the beginning of reperfusion). In unprotected Wistar-Kyoto hearts, used as normal counterpart, infarct-size resulted smaller than in SHR. CST-Post reduced significantly infarct-size and improved post-ischemic cardiac function in both strains. After 20-min reperfusion, CST-Post induced S-nitrosylation of calcium channels and phosphorylation of RISK-pathway in WKY and SHR hearts. Yet specific inhibitors of the RISK pathway blocked the CST-Post protective effects against infarct in the 120-min reperfusion groups. Moreover, apoptosis (evaluated by TUNEL, ARC and cleaved caspase) was reduced by CST-Post. Importantly, CST-Post increased expression of pro-angiogenetic factors (i.e., HIF-1\u03b1 and eNOS expression) after two-hour reperfusion.",
            "output": [
                "Does catestatin increase the expression of anti-apoptotic and pro-angiogenetic factors in the post-ischemic hypertrophied heart of SHR?"
            ]
        },
        {
            "id": "task847-fc2c3c3909944ce3b45d176a57413807",
            "input": "Several studies have shown that contralateral prophylactic mastectomy (CPM) provides a disease-free and overall survival (OS) benefit in young women with estrogen receptor (ER)-negative breast cancer. We utilized the National Cancer Data Base to evaluate CPM's survival benefit for young women with early -stage breast cancer in the years that ER status was available.\", 'We selected 14,627 women \u226445 years of age with American Joint Committee on Cancer stage I-II breast cancer who underwent unilateral mastectomy or CPM from 2004 to 2006. Five-year OS was compared between those who had unilateral mastectomy and CPM using the Kaplan-Meier method and Cox regression analysis.', 'A total of 10,289 (70.3 %) women underwent unilateral mastectomy and 4,338 (29.7 %) women underwent CPM. Median follow up was 6.1 years. After adjusting for patient age, race, insurance status, co-morbidities, year of diagnosis, ER status, tumor size, nodal status, grade, histology, facility type, facility location, use of adjuvant radiation and chemohormonal therapy, there was no difference in OS in women <45 years of age who underwent CPM compared towith those who underwent unilateral mastectomy (hazard ratio [HR] = 0.93; p = 0.39). In addition, Tthere was no improvement in OS in women <45 years of age with T1N0 tumors who underwent CPM versus unilateral mastectomy (HR = 0.85; p = 0.37) after adjusting for the aforementioned factors. Among women \u226445 years of age with ER-negative tumors who underwent CPM, there was no improvement in OS compared with women who underwent unilateral mastectomy (HR = 1.12; p = 0.32) after adjusting for the same aforementioned factors.",
            "output": [
                "Does contralateral prophylactic mastectomy provide no survival benefit in young women with estrogen receptor-negative breast cancer?"
            ]
        },
        {
            "id": "task847-f80b1c37c4b846a49fdefee7107a46cd",
            "input": "Type 2 diabetes is known to be associated with elevated cardiovascular mortality. Pioglitazone improves blood pressure (BP) and pulse wave velocity (PWV), which is an arterial stiffness parameter. Arterial stiffness is closely associated with cardiovascular disease. However, PWV is correlated with BP. The cardio-ankle vascular index (CAVI) reflects arterial stiffness independent of BP. Pioglitazone improves PWV but reduces blood pressure. The aim of this study was to re-evaluate the effect of pioglitazone on arterial stiffness with CAVI.', 'Sixty patients with type 2 diabetes mellitus and already on 500 mg/day of metformin received add-on therapy of pioglitazone 15 mg/day or glimepiride 1 mg/day for 6 months, during which time changes in their metabolic parameters and CAVI were observed.', 'After 6 months of treatment, both pioglitazone (n=30) and glimepiride (n=30) improved fasting blood glucose and glycated hemoglobin. The changes in fasting blood glucose and glycated hemoglobin between the two groups were greater in the pioglitazone group. Systolic and diastolic BP was decreased in both groups, with no significant between-group differences. Only pioglitazone increased serum adiponectin levels, and the change in adiponectin between the pioglitazone and glimepiride groups was significantly different. CAVI was decreased significantly by pioglitazone but remained unchanged after treatment with glimepiride. The change in CAVI between the two groups was significantly different.",
            "output": [
                "Does pioglitazone improve the cardio-ankle vascular index in patients with type 2 diabetes mellitus treated with metformin?"
            ]
        },
        {
            "id": "task847-f634c735159146c69c0e2127aa0262cf",
            "input": "Alterations of adipocytokine levels and clinical parameters in non-alcoholic fatty liver disease (NAFLD) are crucial for the prognosis and complications of the diseases. However, the key adipocytokines independently associated with NAFLD have not been identified, and we aimed to investigate them.', \"This study was conducted on a consecutive series of 210 Taiwanese NAFLD patients and 420 sex- and age-matched controls. Fatty liver was diagnosed by magnetic resonance spectroscopy. The enrolled subjects' body mass indexes, homeostasis model of assessment-insulin resistance, uric acid, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, blood pressure, metabolic syndrome (yes/no), alanine aminotransferase, aspartate aminotransferase-to-platelet ratio indexes, leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were analyzed to determine their association with NAFLD.\", 'Univariate analysis showed that all of the aforementioned factors were associated with NAFLD, whereas multivariate analysis revealed that only PAI-1 (odds ratio: 1.39, P\\u2009=\\u20090.039) was independently associated with NAFLD. Subgroup analysis showed that females consistently had higher leptin (P\\u2009<\\u20090.001) and adiponectin (P\\u2009<\\u20090.001) levels than males, whereas their PAI-1 levels were similar. Males with NAFLD had higher leptin but lower adiponectin levels than their subgroup counterparts (all P\\u2009<\\u20090.001). Among the female subgroups, hyperleptinemia and hypoadiponectinemia were only observed in the NAFLD patients \u2265\\u200945 years.",
            "output": [
                "Is plasminogen activator inhibitor-1 independently associated with non-alcoholic fatty liver disease whereas leptin and adiponectin vary between genders?"
            ]
        },
        {
            "id": "task847-70039a6fe2894daba091aaf133eaff39",
            "input": "Continuous support from follicular CD4(+) T helper (Tfh) cells drives germinal center (GC) responses, which last for several weeks to produce high affinity memory B cells and plasma cells. In autoimmune Sle1 and NZB/W F1 mice, elevated numbers of Tfh cells persist, promoting the expansion of self-reactive B cells. Expansion of circulating Tfh like cells have also been described in several autoimmune diseases. Although, the signals required for Tfh differentiation have now been well described, the mechanisms that sustain the maintenance of fully differentiated Tfh are less understood. Recent data demonstrate a role for GC B cells for Tfh maintenance after protein immunization.', 'Given the pathogenic role Tfh play in autoimmune disease, we explored whether B cells are required for maintenance of autoreactive Tfh. Our data suggest that the number of mature autoreactive Tfh cells is controlled by GC B cells. Depletion of B cells in Sle1 autoimmune mice leads to a dramatic reduction in Tfh cells. In NZB/W F1 autoimmune mice, similar to the SRBC immunization model, GC B cells support the maintenance of mature Tfh, which is dependent mainly on ICOS. The CD28-associated pathway is dispensable for Tfh maintenance in SRBC immunized mice, but is required in the spontaneous NZB/W F1 model.",
            "output": [
                "Does germinal center B cell depletion diminish CD4+ follicular T helper cells in autoimmune mice?"
            ]
        },
        {
            "id": "task847-04616d9522dc407a8b8d035653aa06f6",
            "input": "To analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified Sharp/van der Heijde score and radiographic progression was defined as an increase in the total Sharp score above 5.8 (the smallest detectable change).', 'Prospective, randomised study of patients with early RA.', 'Secondary level of care; six participating centres from southern Sweden; both urban and rural populations.', 'In all, 225 patients, 64% women, with a diagnosis of RA according to the American College of Rheumatology criteria, were included if they were between 18 and 80\\u2005years of age and had a disease duration of less than 1\\u2005year.', 'The patients were randomised to 7.5\\u2005mg prednisolone daily for 2\\u2005years (P-group; n=108) or no prednisolone (NoP-group; n=117) when they started with their first disease-modifying anti-rheumatic drug and were prospectively followed for 2\\u2005years.', 'The frequency of patients with radiographic progression after 2\\u2005years was 26% in the P-group and 39% in the NoP-group (p=0.033). Relevant interactions between treatment and rheumatoid factor (RF) (p=0.061) and between treatment and anti-cyclic citrullinated peptide 2 (anti-CCP) (p=0.096) were found. RF and anti-CCP independently predicted radiographic progression only in the NoP-group, OR (95% CI) 9.4 (2.5 to 35.2), p=0.001 and OR (95% CI) 8.7 (2.5 to 31.3), p=0.001, respectively.",
            "output": [
                "Do rheumatoid factor and anti-CCP predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone : a randomised study?"
            ]
        },
        {
            "id": "task847-73a0cbfb753a46d5a55b3a1f339901db",
            "input": "Proteins from the ABC family (ATP-binding cassette) represent the largest known group of efflux pumps, responsible for transporting specific molecules across lipid membranes in both prokaryotic and eukaryotic organisms. In arthropods they have been shown to play a role in insecticide defense/resistance. The presence of ABC transporters and their possible association with insecticide transport have not yet been investigated in the mosquito Anopheles stephensi, the major vector of human malaria in the Middle East and South Asian regions. Here we investigated the presence and role of ABCs in transport of permethrin insecticide in a susceptible strain of this mosquito species.', 'To identify ABC transporter genes we obtained a transcriptome from untreated larvae of An. stephensi and then compared it with the annotated transcriptome of Anopheles gambiae. To analyse the association between ABC transporters and permethrin we conducted bioassays with permethrin alone and in combination with an ABC inhibitor, and then we investigated expression profiles of the identified genes in larvae exposed to permethrin.', 'Bioassays showed an increased mortality of mosquitoes when permethrin was used in combination with the ABC-transporter inhibitor. Genes for ABC transporters were detected in the transcriptome, and five were selected (AnstABCB2, AnstABCB3, AnstABCB4, AnstABCmember6 and AnstABCG4). An increased expression in one of them (AnstABCG4) was observed in larvae exposed to the LD50 dose of permethrin. Contrary to what was found in other insect species, no up-regulation was observed in the AnstABCB genes.",
            "output": [
                "Are aBC transporters involved in defense against permethrin insecticide in the malaria vector Anopheles stephensi?"
            ]
        },
        {
            "id": "task847-28b3a6bb50684414bc9160eda81d80ec",
            "input": "The molecular mechanisms underlying dysregulation of microRNAs have been documented in nasopharyngeal carcinoma (NPC). Our previous study demonstrated that plasma miR-124 was down-regulated in NPC using microarray analysis and quantitative PCR validation. Though growing studies showed that down-regulated miR-124 was closely related to tumourigenesis in various types of cancers, the role of miR-124 in NPC remains largely unknown.', 'The expression level of miR-124 was evaluated in NPC cell lines and patient specimens using quantitative reverse transcription-PCR (Real-time qPCR). The clinicopathological significance of the resultant data was later analyzed. Then, we explored the role of miR-124 in NPC tumorigenesis by in vitro and in vivo experiments. Homo sapiens forkhead box Q1 (Foxq1) was confirmed as a novel direct target gene of miR-124 by the dual-luciferase assay and western bolt.', 'We found that miR-124 was commonly down-regulated in NPC specimens and NPC cell lines. The expression of miR-124 was inversely correlation with clinical stages and marked on T stages. Then, the ectopic expression of miR-124 dramatically inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Furthermore, we identified Foxq1 as a novel direct target of miR-124. Functional studies showed that knockdown of Foxq1 inhibited cell growth, migration and invasion, whereas Foxq1 overexpression partially rescued the suppressive effect of miR-124 in NPC. In clinical specimens, Foxq1 was commonly up-regulated in NPC, and the level increased with clinical stages and T stages. Additionally, the level of Foxq1 was inversely correlated with miR-124.",
            "output": [
                "Does miR-124 suppress tumor growth and metastasis by targeting Foxq1 in nasopharyngeal carcinoma?"
            ]
        },
        {
            "id": "task847-e39aba07e6bb4158bb4cc5b6cdb2ce84",
            "input": "Hashimoto's thyroiditis (HT) is considered to be a Th1-related autoimmune disease (AID). Recent studies revealed that Th17 lymphocytes (producing mostly IL-17, IL-21 and IL-22) play a major role in numerous AIDs commonly thought to be Th1 diseases. More recently, another subset of Th cells, which produce IL-22 and thus so-called Th-22, have been identified. Few data are available in the literature on the role of IL-22, the main soluble mediator of both Th17 and Th22 cells, in HT.\", 'Using IL-22 Quantikine ELISA Kit (lower limit of detection 0.7 pg/ml), we assayed serum levels of IL-22 in three groups of subjects: newly diagnosed HT patients (n=55, 5 males and 50 females, age 38\u00b117 years), non-HT patients with nodular goiter (n=30, 4 males and 26 females, age 43\u00b114 years) and an age- and sex-matched group of healthy individuals. HT patients were euthyroid and were not receiving any treatment.', 'HT patients showed significantly higher levels of serum IL-22 (group A, 42\u00b134 pg/ml) as compared to non-HT-goitrous patients (18\u00b115 pg/ml; P<0.001) and healthy controls (20\u00b113 pg/ml; P=0.014). Serum IL-22 levels did not differ between non-HT-goitrous patients and healthy controls (p=0.496). No significant correlation was found between serum levels of IL-22 and Tg-Ab, TPO-Ab or TSH in the HT patients.",
            "output": [
                "Is serum interleukin-22 ( IL-22 ) increased in the early stage of Hashimoto 's thyroiditis compared to non-autoimmune thyroid disease and healthy controls?"
            ]
        },
        {
            "id": "task847-99c0d686bf534a44a2878450de814b42",
            "input": "Apart from transcription factors, little is known about the molecules that modulate the proliferation and differentiation of pancreatic endocrine cells. The early expression of tyrosine hydroxylase (TH) in a subset of glucagon(+) cells led us to investigate whether catecholamines have a role in beta cell development.', 'We studied the immunohistochemical characteristics of TH-expressing cells in wild-type (Th (+/+) ) mice during early pancreas development, and analysed the endocrine pancreas phenotype of TH-deficient (Th (-/-) ) mice. We also studied the effect of dopamine addition and TH-inhibition on insulin-producing cells in explant cultures.', 'In the mouse pancreas at embryonic day (E)12.5-E13.5, the \u223c10% of early glucagon(+) cells that co-expressed TH rarely proliferated and did not express the precursor marker neurogenin 3 at E13.5. The number of insulin(+) cells in the Th (-/-) embryonic pancreas was decreased as compared with wild-type embryos at E13.5. While no changes in pancreatic and duodenal homeobox 1 (PDX1)(+)-progenitor cell number were observed between groups at E12.5, the number of neurogenin 3 and NK2 homeobox 2 (NKX2.2)-expressing cells was reduced in Th (-/-) embryonic pancreas, an effect that occurred in parallel with increased expression of the transcriptional repressor Hes1. The potential role of dopamine as a pro-beta cell stimulus was tested by treating pancreas explants with this catecholamine, which resulted in an increase in total insulin content and insulin(+) cells relative to control explants.",
            "output": [
                "Is non-neural tyrosine hydroxylase , via modulation of endocrine pancreatic precursors , required for normal development of beta cells in the mouse pancreas?"
            ]
        },
        {
            "id": "task847-df92c147fcb74967817b330a9d134c28",
            "input": "Macrophage accumulation of cholesterol leads to foam cell formation which is a major pathological event of atherosclerosis. Recent studies have shown that microRNA (miR)-19b might play an important role in cholesterol metabolism and atherosclerotic diseases. Here, we have identified miR-19b binding to the 3'UTR of ATP-binding cassette transporter A1 (ABCA1) transporters, and further determined the potential roles of this novel interaction in atherogenesis.\", 'To investigate the molecular mechanisms involved in a miR-19b promotion of macrophage cholesterol accumulation and the development of aortic atherosclerosis.', \"We performed bioinformatics analysis using online websites, and found that miR-19b was highly conserved during evolution and directly bound to ABCA1 mRNA with very low binding free energy. Luciferase reporter assay confirmed that miR-19b bound to 3110-3116 sites within ABCA1 3'UTR. MiR-19b directly regulated the expression levels of endogenous ABCA1 in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by qRT-PCR and western blot. Cholesterol transport assays revealed that miR-19b dramatically suppressed apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux, resulting in the increased levels of total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) as revealed by HPLC. The excretion of (3)H-cholesterol originating from cholesterol-laden MPMs into feces was decreased in mice overexpressing miR-19b. Finally, we evaluated the proatherosclerotic role of miR-19b in apolipoprotein E deficient (apoE(-/-)) mice. Treatment with miR-19b precursor reduced plasma high-density lipoprotein (HDL) levels, but increased plasma low-density lipoprotein (LDL) levels. Consistently, miR-19b precursor treatment increased aortic plaque size and lipid content, but reduced collagen content and ABCA1 expression. In contrast, treatment with the inhibitory miR-19b antisense oligonucleotides (ASO) prevented or reversed these effects.",
            "output": [
                "Does microRNA-19b promote macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1?"
            ]
        },
        {
            "id": "task847-00dc5dc2940d466baedd985244efc904",
            "input": "Worldwide, each year, large numbers of women are referred for colposcopy following low-grade abnormal cervical cytology. Many have no visible abnormality on examination. The risk of cervical intra-epithelial neoplasia grade 2/3 (CIN2/3) in these women is low. It is unknown whether, for women, a normal colposcopy resolves the anxiety which often follows the receipt of an abnormal cytology result. We investigated the prevalence of adverse psychological outcomes over 30\\xa0months following a normal colposcopy.', 'This cohort study was nested within the UK TOMBOLA randomized controlled trial. Women aged 20-59\\xa0years, with recent low-grade cytology, who had a satisfactory colposcopy examination and normal transformation zone, completed the Hospital Anxiety and Depression Scale (HADS) and Process Outcome Specific Measure (POSM) at recruitment and during follow-up (12, 18, 24 and 30\\xa0months post-recruitment). Outcomes included percentages reporting significant anxiety (HADS anxiety subscale score \u226511), significant depression (HADS depression subscale score \u22658) or worries about the result of the next cytology test, cervical cancer, having sex, future fertility and general health at each time point (point prevalence) and during follow-up (cumulative prevalence).', 'The study included 727 women. All psychological measures (except depression) had high prevalence at recruitment, falling substantially by 12\\xa0months. During follow-up, the cumulative prevalence of significant anxiety was 27% and significant depression was 21%. The most frequently reported worry was that the next cytology test would be abnormal (cumulative prevalence of 71%; point prevalence of \u226550% at 12 and 18\\xa0months). The cumulative prevalence values of worries about cervical cancer, having sex and future fertility were 33%, 20% and 16%, respectively.",
            "output": [
                "Does a normal colposcopy examination fail to provide psychological reassurance for women who have had low-grade abnormal cervical cytology?"
            ]
        },
        {
            "id": "task847-4361be4d8e5546b191718a741179d27d",
            "input": "Eph receptors, comprising the A- and B-subfamilies, are the largest family of receptor tyrosine kinases in the mammalian genome, and their function is critical for morphogenesis in a variety of contexts. Whereas signaling through B-type Ephs has been demonstrated to play a role in cleft lip and palate (CL/P), the involvement of A-type Ephs has not been examined in this context notwithstanding a recent genome-wide association study that identified the EPHA3 locus as a candidate for non-syndromic CL/P.', 'Here, we present a systematic analysis of the gene expression patterns for the nine EphA receptors at progressive stages of mouse development and find that EphA3, EphA4, and EphA7 exhibit restricted overlapping patterns of expression during palate development. We find that homozygous mutation of EphA3 or compound homozygous mutation of EphA3 and EphA4 in mice does not result in defective midfacial development, supporting the possibility of redundant function with EphA7. We also document previously undescribed expression patterns in other tissues of the craniofacial complex including the lacrimal duct and salivary glands.",
            "output": [
                "Does embryonic expression of EphA receptor genes in mice support their candidacy for involvement in cleft lip and palate?"
            ]
        },
        {
            "id": "task847-d7fc47b3c82644a48116eb7d0a82283b",
            "input": "MDC1A is a congenital neuromuscular disorder with developmentally complex and progressive pathologies that results from a deficiency in the protein laminin \u03b12. MDC1A is associated with a multitude of pathologies, including increased apoptosis, inflammation and fibrosis. In order to assess and treat a complicated disease such as MDC1A, we must understand the natural history of the disease so that we can identify early disease drivers and pinpoint critical time periods for implementing potential therapies.', 'We found that DyW mice show significantly impaired myogenesis and high levels of apoptosis as early as postnatal week 1. We also saw a surge of inflammatory response at the first week, marked by high levels of infiltrating macrophages, nuclear factor \u03baB activation, osteopontin expression and overexpression of inflammatory cytokines. Fibrosis markers and related pathways were also observed to be elevated throughout early postnatal development in these mice, including periostin, collagen and fibronectin gene expression, as well as transforming growth factor \u03b2 signaling. Interestingly, fibronectin was found to be the predominant fibrous protein of the extracellular matrix in early postnatal development. Lastly, we observed upregulation in various genes related to angiotensin signaling.', 'We sought out to examine the dysregulation of various pathways throughout early development (postnatal weeks 1-4) in the DyW mouse, the most commonly used mouse model of laminin-deficient muscular dystrophy. Muscle function tests (stand-ups and retractions) as well as gene (qRT-PCR) and protein levels (western blot, ELISA), histology (H&E, picrosirius red staining) and immunohistochemistry (fibronectin, TUNEL assay) were used to assess dysregulation of matricelluar protieins.",
            "output": [
                "Is dysregulation of matricellular proteins an early signature of pathology in laminin-deficient muscular dystrophy?"
            ]
        },
        {
            "id": "task847-1d5a0c3c71444295971fc41245ec862b",
            "input": "Tubuloglomerular feedback (TGF) is an important mechanism in control of signal nephron glomerular filtration rate. The oxidative stress in the macula densa, primarily determined by the interactions between nitric oxide (NO) and superoxide (O2-), is essential in maintaining the TGF responsiveness. However, few studies examining the interactions between and amount of NO and O2- generated by the macula densa during normal and hypertensive states.', 'In this study, we used isolated perfused juxtaglomerular apparatus to directly measure the amount and also studied the interactions between NO and O2- in macula densa in both physiological and slow pressor Angiotensin II (Ang II)-induced hypertensive mice.', 'We found that slow pressor Ang II at a dose of 600\\xa0ng kg(-1) min(-1) for two weeks increased mean arterial pressure by 26.1\\xa0\u00b1 5.7\\xa0mmHg. TGF response increased from 3.4\\xa0\u00b1\\xa00.2\\xa0\u03bcm in control to 5.2\\xa0\u00b1\\xa00.2\\xa0\u03bcm in hypertensive mice. We first measured O2- generation by the macula densa and found it was undetectable in control mice. However, O2- generation by the macula densa increased to 21.4\\xa0\u00b1\\xa02.5 unit min(-1) in Ang II-induced hypertensive mice. We then measured NO generation and found that NO generation by the macula densa was 138.5\\xa0\u00b1\\xa09.3 unit min(-1) in control mice. The NO was undetectable in the macula densa in hypertensive mice infused with Ang II.",
            "output": [
                "Does oxidative status in the macula densa modulate tubuloglomerular feedback responsiveness in angiotensin II-induced hypertension?"
            ]
        },
        {
            "id": "task847-d06cf55f98d3401584fa13579c2e6f5c",
            "input": "To date, Alphavirus infections and their most prominent member, chikungunya fever, a viral disease which first became apparent in Tanzania in 1953, have been very little investigated in regions without epidemic occurrence. Few data exist on burden of disease and socio-economic and environmental covariates disposing to infection.', 'A cross-sectional seroprevalence study was undertaken in 1,215 persons from Mbeya region, South-Western Tanzania, to determine the seroprevalence of anti-Alphavirus IgG antibodies, and to investigate associated risk factors.', '18% of 1,215 samples were positive for Alphavirus IgG. Seropositivity was associated with participant age, low to intermediate elevation, flat terrain and with IgG positivity for Rift Valley fever, Flaviviridae, and rickettsiae of the spotted fever group. When comparing the geographical distribution of Alphavirus seropositivity to that of Rift Valley fever, it was obvious that Alphaviruses had spread more widely throughout the study area, while Rift Valley fever was concentrated along the shore of Lake Malawi.",
            "output": [
                "Does seroprevalence of alphavirus antibodies in a cross-sectional study in southwestern Tanzania suggest endemic circulation of chikungunya?"
            ]
        },
        {
            "id": "task847-dc8322e60de048d9868eb8b5d5c98546",
            "input": "MiR-506 is a miRNA involved in carcinogenesis of several kinds of cancer. In this study, we explored whether miR-506 played a critical role in hepatocellular carcinoma (HCC).', 'Twenty HCC and adjacent normal liver tissue samples were collected. Human hepatoma cell lines HepG2 and H7402 were used for in vitro studies. The expression of miR-506 and transcriptional co-activator YAP was examined using qRT-PCR. Western blot analysis was used to measure the expression of YAP and its target genes. Luciferase reporter gene assay was used to identify YAP as a target gene of miR-506. MTT and EdU assays were carried out for functional analysis.', \"The expression of miR-506 was significantly lower in HCC than in adjacent normal liver tissues. Bioinformatics analysis revealed that YAP mRNA might be one of the targets of miR-506, and miR-506 in HCC tissues was found to be negatively correlated with YAP (r=-0.605). In both HepG2 and H7402 cells, miR-506 dose-dependently down-regulated YAP and its target genes c-Myc and the connective tissue growth factor (CTGF). Luciferase reporter gene assays demonstrated that miR-506 targeted the wild type 3'UTR of YAP mRNA, but not a 3'UTR with a mutant seed site. Furthermore, miR-506 significantly inhibited the proliferation of HepG2 and H7402 cells, while anti-miR-506 enhanced the cell proliferation, which was blocked by YAP siRNA.",
            "output": [
                "Does miR-506 suppress proliferation of hepatoma cells through targeting YAP mRNA 3'UTR?"
            ]
        },
        {
            "id": "task847-4eddf5bab6404087953e168275ed0ae3",
            "input": "Ursolic acid (UA) is a pentacyclic triterpenoid found in most plant species, which has been shown anti-inflammatory and anti-oxidative activities. In this study, we examined the effects of UA on collagen-induced arthritis (CIA) in mice, and to identify the mechanisms underlying the effects.', 'CIA was induced in mice. Two weeks later, the mice were treated with UA (150 mg/kg, ip, 3 times per week) for 4 weeks. The expression of cytokines and oxidative stress markers in joint tissues was measured with immunohistochemistry. The numbers of CD4+IL-17+, CD4+CD25+Foxp3+ and pSTAT3 cells in spleens were determined using confocal immunostaining or flowcytometric analyses. Serum antibody levels and B cell-associated marker mRNAs were analyzed with ELISAs and qRT-PCR, respectively. CD4+ T cells and CD19+ B cells were purified from mice spleens for in vitro studies.', 'UA treatment significantly reduced the incidence and severity of CIA-induced arthritis, accompanied by decreased expression of proinflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6, IL-21 and IL-17) and oxidative stress markers (nitrotyrosine and iNOS) in arthritic joints. In CIA mice, UA treatment significantly decreased the number of Th17 cells, while increased the number of Treg cells in the spleens, which was consistent with decreased expression of pSTAT3, along with IL-17 and ROR\u03b3t in the splenocytes. In addition, UA treatment significantly reduced the serum CII-specific IgG levels in CIA mice. The inhibitory effects of UA on Th17 cells were confirmed in an in vitro model of Th17 differentiation. Furthermore, UA dose-dependently suppressed the expression of B cell-associated markers Bcl-6, Blimp1 and AID mRNAs in purified CD19+ B cells pretreated with IL-21 or LPS in vitro.",
            "output": [
                "Does ursolic acid ameliorate autoimmune arthritis via suppression of Th17 and B cell differentiation?"
            ]
        },
        {
            "id": "task847-1a2c1d26c1b542448f108a23be4b1de7",
            "input": "To investigate the mechanisms of anti-atherosclerotic action of ezetimibe in rat vascular smooth muscle cells (VSMCs) in vitro.', 'VSMCs of SD rats were cultured in the presence of Chol:M\u03b2CD (10 \u03bcg/mL) for 72 h, and intracellular lipid droplets and cholesterol levels were evaluated using Oil Red O staining, HPLC and Enzymatic Fluorescence Assay, respectively. The expression of caveolin-1, sterol response element-binding protein-1 (SREBP-1) and ERK1/2 were analyzed using Western blot assays. Translocation of SREBP-1 and ERK1/2 was detected with immunofluorescence.', 'Treatment with Chol:M\u03b2CD dramatically increased the cellular levels of total cholesterol (TC), cholesterol ester (CE) and free cholesterol (FC) in VSMCs, which led to the formation of foam cells. Furthermore, Chol:M\u03b2CD treatment significantly decreased the expression of caveolin-1, and stimulated the expression and nuclear translocation of SREBP-1 in VSMCs. Co-treatment with ezetimibe (3 \u03bcmol/L) significantly decreased the cellular levels of TC, CE and FC, which was accompanied by elevation of caveolin-1 expression, and by a reduction of SREBP-1 expression and nuclear translocation. Co-treatment with ezetimibe dose-dependently decreased the expression of phosphor-ERK1/2 (p-ERK1/2) in VSMCs. The ERK1/2 inhibitor PD98059 (50 \u03bcmol/L) altered the cholesterol level and the expression of p-ERK1/2, SREBP-1 and caveolin-1 in the same manner as ezetimibe did.",
            "output": [
                "Does ezetimibe suppress cholesterol accumulation in lipid-loaded vascular smooth muscle cells in vitro via MAPK signaling?"
            ]
        },
        {
            "id": "task847-416a02ee7585408fb2cf8958600cfbea",
            "input": "To investigate the mechanisms underlying the hepatotoxicity of timosaponin A3 (TA3), a steroidal saponin from Anemarrhena asphodeloides, in rats.', 'Male SD rats were administered TA3 (100 mg\u00b7kg(-1)\u00b7d(-1), po) for 14 d, and the blood and bile samples were collected after the final administration. The viability of a sandwich configuration of cultured rat hepatocytes (SCRHs) was assessed using WST-1. Accumulation and biliary excretion index (BEI) of d8-TCA in SCRHs were determined with LC-MS/MS. RT-PCR and Western blot were used to analyze the expression of relevant genes and proteins. ROS and ATP levels, and mitochondrial membrane potential (MMP) were measured. F-actin cytoskeletal integrity was assessed under confocal microscopy.', 'TA3 administration in rats significantly elevated the total bile acid in serum, and decreased bile acid (BA) component concentrations in bile. TA3 inhibited the viability of the SCRHs with an IC50 value of 15.21\u00b11.73 \u03bcmol/L. Treatment of the SCRHs with TA3 (1-10 \u03bcmol/L) for 2 and 24 h dose-dependently decreased the accumulation and BEI of d8-TCA. The TA3 treatment dose-dependently decreased the expression of BA transporters Ntcp, Bsep and Mrp2, and BA biosynthesis related Cyp7a1 in hepatocytes. Furthermore, the TA3 treatment dose-dependently increased ROS generation and HO-1 expression, decreased the ATP level and MMP, and disrupted F-actin in the SCRHs. NAC (5 mmol/L) significantly ameliorated TA3-induced effects in the SCRHs, whereas mangiferin (10-200 \u03bcg/mL) almost blocked TA3-induced ROS generation.",
            "output": [
                "Does timosaponin A3 induce hepatotoxicity in rats through inducing oxidative stress and down-regulating bile acid transporters?"
            ]
        },
        {
            "id": "task847-ed67e559726c4727a072497fe2d0b501",
            "input": "Hepatocyte-like cells, differentiated from different stem cell sources, are considered to have a range of possible therapeutic applications, including drug discovery, metabolic disease modelling, and cell transplantation. However, little is known about how stem cells differentiate into mature and functional hepatocytes.', 'Using transcriptomic screening, a transcription factor, liver X receptor \u03b1 (NR1H3), was identified as increased during HepaRG cell hepatogenesis; this protein was also upregulated during embryonic stem cell and induced pluripotent stem cell differentiation.', 'Overexpressing NR1H3 in human HepaRG cells promoted hepatic maturation; the hepatocyte-like cells exhibited various functions associated with mature hepatocytes, including cytochrome P450 (CYP) enzyme activity, secretion of urea and albumin, upregulation of hepatic-specific transcripts and an increase in glycogen storage. Importantly, the NR1H3-derived hepatocyte-like cells were able to rescue lethal fulminant hepatic failure using a non-obese diabetic/severe combined immunodeficient mouse model.",
            "output": [
                "Does liver X receptor \u03b1 ( LXR\u03b1/NR1H3 ) regulate differentiation of hepatocyte-like cells via reciprocal regulation of HNF4\u03b1?"
            ]
        },
        {
            "id": "task847-55fc002995304e0a977ba917e95fd968",
            "input": "Comatose patients resuscitated after out-of-hospital cardiac arrest receive therapeutic hypothermia. Bradycardia is frequent during therapeutic hypothermia, but its impact on outcome remains unclear. We explore a possible association between bradycardia during therapeutic hypothermia and neurologic outcome in comatose survivors of out-of-hospital cardiac arrest.', 'Retrospective cohort study, from January 2009 to January 2011.', 'University hospital medical and cardiac ICUs.', 'One hundred eleven consecutive comatose out-of-hospital cardiac arrest patients treated with therapeutic hypothermia.', 'Patients treated with standardized treatment protocol after cardiac arrest.', \"All out-of-hospital cardiac arrest patients' records were reviewed. Hemodynamic data were obtained every fourth hour during the first days. The patients were in temperature target range (32-34\u00b0C) 8 hours after out-of-hospital cardiac arrest and dichotomized into bradycardia and nonbradycardia groups depending on their actual heart rate less than or equal to 60 beats/min or more than 60 beats/min at that time. Primary endpoint was Cerebral Performance Category score at hospital discharge. More nonbradycardia group patients received epinephrine during resuscitation and epinephrine and norepinephrine in the early in-hospital period. They also had lower base excess at admission. Survival rate with favorable outcome was significantly higher in the bradycardia than the nonbradycardia group (60% vs 37%, respectively, p = 0.03). For further heart rate quantification, patients were divided into quartiles: less than or equal to 49 beats/min, 50-63 beats/min, 64-77 beats/min, and more than or equal to 78 beats/min, with respective proportions of patients with good outcome at discharge of 18 of 27 (67%), 14 of 25 (56%), 12 of 28 (43%), and 7 of 27 (26%) (p = 0.002). Patients in the lowest quartile had significantly better outcome than the higher groups (p = 0.027), whereas patients in the highest quartile had significantly worse outcome than the lower three groups (p = 0.013).",
            "output": [
                "Is bradycardia during therapeutic hypothermia associated with good neurologic outcome in comatose survivors of out-of-hospital cardiac arrest?"
            ]
        },
        {
            "id": "task847-dda73ea69b8c4811805510d43b492053",
            "input": "BRAF mutations occur in 5% to 10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described.', 'We searched the M.D. Anderson Cancer Center databases for patients with colorectal cancer and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, PFS, overall survival, and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method.', 'Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first 3 lines of chemotherapy, median PFS was 6.3 months (n\\xa0= 69 patients; 95% confidence interval [CI], 4.9-7.7 months), 2.5 months (n\\xa0= 58 patients; 95% CI, 1.8-3.0 months), and 2.6 months (n\\xa0= 31 patients; 95% CI, 1.0-4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively; P\\xa0= .99).",
            "output": [
                "Does progression-free survival remain poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer?"
            ]
        },
        {
            "id": "task847-3cdb988eaed647fc98af94f0724689d8",
            "input": "Long-term results of a study investigating potential prognostic factors for treatment outcomes in patients with stage III esophageal cancer are presented.', 'In 64 patients, the impact of tumor cell expression of erythropoietin (EPO) and erythropoietin-receptor (EPO-R) and ten additional factors (age, gender, performance status, tumor length, tumor stage (T-stage), nodes (N-stage), histology/grading, hemoglobin levels during radiotherapy, surgery) on survival and loco-regional control was evaluated up to 10 years following radio-chemotherapy.', 'On multivariate analysis, improved survival was associated with low EPO-R expression (p=0.034) and hemoglobin levels during radiotherapy \u2265 12 g/dl (p=0.026). Low EPO expression was associated with survival on univariate (p=0.010) but not on multivariate analysis (p=0.42). On multivariate analysis, improved loco-regional control was significantly associated with hemoglobin levels during radiotherapy \u2265 12 g/dl (p<0.001).",
            "output": [
                "Are biologic factors associated with tumor oxygenation prognostic in patients with stage III esophageal cancer : long-term results?"
            ]
        },
        {
            "id": "task847-6c3a97b0b18f43c6b16273bcb42c21d2",
            "input": "Our previous work demonstrated altered messenger RNA expression of integrin \u03b2-5 and -8, using an in silico analysis of publically available data from patients with biliary atresia (BA); however, we were unable to demonstrate statistically significant differences in protein expression because of sample size. In the present study, we repeated the analysis of liver fibrosis and protein expression of the integrins in a larger cohort of patients with BA and compared them with patients undergoing liver biopsy for other diagnoses, with the hypothesis that \u2265 1 of the integrins would be differentially expressed.', 'Liver specimens were obtained at 2 collaborating institutions. Samples from infants with BA (n = 23) were compared with samples from those who underwent liver biopsy for neonatal hepatitis (n = 9). All of the specimens were analyzed by 2 pathologists (C.R. and R.A.), who were blinded to the diagnoses. Standard Ishak scoring was performed to evaluate fibrosis and inflammation, and immunohistochemical (IHC) positivity was graded from 0 to 4. Comparisons between the IHC positivity and Ishak scoring for the BA and control groups were performed using the Student t test with P < 0.01 considered significant because of the multiple comparisons. Interobserver variability was assessed by intraclass correlation (ICC).', 'Pooled analysis from specimens from patients with BA showed significantly more fibrosis than controls based on Ishak scores (3.21 \u00b1 1.82 vs 1.17 \u00b1 1.00, P < 0.005). IHC evaluation showed increased integrin \u03b1\u03bd\u03b28 protein expression when compared with controls (2.67 \u00b1 0.81 vs 1.72 \u00b1 0.62, P < 0.005); however, there were no significant differences in integrin \u03b1\u03bd\u03b25 (1.93 \u00b1 0.84 vs 1.50 \u00b1 0.90, P = 0.23) or integrin \u03b1\u03bd\u03b26 (0.85 \u00b1 1.20 vs 0.94 \u00b1 0.85, P = 0.82) expression. These data were confirmed on individual analysis. Interobserver agreement was fair for integrin \u03b1\u03bd\u03b25 (ICC 0.52), good for integrin \u03b1\u03bd\u03b26 (ICC 0.72), and excellent for integrin \u03b1\u03bd\u03b28 (ICC 0.79) and fibrosis (ICC 0.89).",
            "output": [
                "Is integrin \u03b2-8 , but not \u03b2-5 or -6 , protein expression increased in livers of children with biliary atresia?"
            ]
        },
        {
            "id": "task847-66a0afe03f31457cbca5df2e7d31ef03",
            "input": "When people are asked to indicate the vanishing location of a moving target, errors in the direction of motion (representational momentum) and in the direction of gravity (representational gravity) are usually found. These errors possess a temporal course wherein the memory for the location of the target drifts downwards with increasing temporal intervals between target's disappearance and participant's responses (representational trajectory).\", 'To assess if representational trajectory is a body-referenced or a world-referenced phenomenon.', \"A behavioral localization method was employed with retention times between 0 and 1400 ms systematically imposed after the target's disappearance. The target could move horizontally (rightwards or leftwards) or vertically (upwards or downwards). Body posture was varied in a counterbalanced order between sitting upright and lying on the side (left lateral decubitus position).\", 'In the upright task, the memory for target location drifted downwards with time in the direction of gravity. This time course did not emerge for the decubitus task, where idiotropic dominance was found.",
            "output": [
                "Is the dynamic representation of gravity suspended when the idiotropic vector is misaligned with gravity?"
            ]
        },
        {
            "id": "task847-49b76ddaefaf43d78771965141fb3dc1",
            "input": "Cardiac carcinoma is the most common subtype of gastric cancer and its incidence has increased in recent years. The current chemotherapeutic drugs exhibit limited effectiveness and significant side effects in patients. Maslinic acid (MA) exerts an anti-tumor activity on a wide range of cancers and has no significant side effect; however, the anti-tumor effect of MA on cardiac carcinoma has not yet been explored.', 'MTT assays, tumor xenograft animal model, immunoblotting, MMP assessment and flow cytometry were performed in this study.', 'MA was able to suppress the viability of cardiac carcinoma cells in both a time- and dose-dependent manner. This natural compound exhibited no cytotoxicity in normal cells. Its inhibitory effect on tumor growth was further confirmed in a mouse model. Mechanistically, MA induced the activation of p38 MAPK in cardiac carcinoma cells and, in turn, changed their mitochondrial membrane potential (MMP). Finally, caspase cascades were activated by a series of cleavages, leading to apoptosis in cardiac cancer cells. Inhibition of p38 MAPK signaling was able to rescue the effect of MA on cardiac carcinoma cells.",
            "output": [
                "Does maslinic acid activate mitochondria-dependent apoptotic pathway in cardiac carcinoma?"
            ]
        },
        {
            "id": "task847-b1517054f74249f8a39bf008d796af00",
            "input": "Type 2 diabetes is known to be associated with increasing cardiovascular mortality. Malondialdehyde-modified LDL (MDA-LDL) is an oxidized LDL and is increased in patients with diabetes or hypertriglyceridemia. Elevated MDA-LDL has been reported to be a risk factor of atherosclerosis or cardiovascular disease. Sitagliptin is a dipeptidyl peptidase-4 inhibitor and a new class of hypoglycemic agents. In this study, the effects of increasing the dose of metformin and add-on sitagliptin on MDA-LDL were examined in type 2 diabetes patients.', 'Seventy patients with type 2 diabetes, inadequately controlled despite on-going treatment with metformin 500 mg/day, were enrolled in this randomized controlled trial. The patients received additional metformin (500 mg/day) or sitagliptin (50 mg/day) for 6 months, and changes in metabolic parameters including MDA-LDL were evaluated.', 'After 6 months of treatment, add-on sitagliptin (n=35) improved fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) to significantly greater extent than increasing the dose of metformin (n=35). There were no differences in total cholesterol and low-density lipoprotein cholesterol levels between two groups. MDA-LDL levels (mean \u00b1 S.E.) decreased significantly with increasing the dose of metformin (from 94.40 \u00b1 6.35 to 77.83 \u00b1 4.74 U/L, P < 0.005), but remained unchanged with add-on sitagliptin treatment (from 89.94 \u00b1 5.59 to 98.46 \u00b1 6.78 U/L, p > 0.05). Multiple linear regression analysis identified increasing the dose of metformin treatment as the only independent factor associated with decreased MDA-LDL (\u03b2 coefficient 0.367, P < 0.0119), and no significant correlation between change in MDA-LDL and fasting blood glucose or HbA1c.",
            "output": [
                "Does metformin reduce circulating malondialdehyde-modified low-density lipoprotein in type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-302447cffee745d2bb1054abb8072ae6",
            "input": "To compare the efficacy of two surgical techniques for controllong nasal width after Le Fort I osteotomy.', \"Fifty-five patients who received the Le Fort I osteotomy have been included in this study. They were randomly divided into 2 groups. The experimental group received extraoral ABS, and the control group received traditional intraoral ABS. 3D photos of the patient's face were taken before operation and at postoperative 3 months. Alar width was measured on the 3D photos. Data was reported as means and standard deviations, and statistic analysis was done by using student t test.\", 'Compared with presurgical data, G. lat-G. lat increased by (2.66 +/- 1.47) mm, Al-Al increased by (2.20 +/- 1.22) mm and Sbal-Sbal increased by (1.30 +/- 1.33) mm in experimental group. G. lat-G. lat increased by (1.38 +/- 1.29) mm, Al-Al increased by (1.06 +/- 0.95) mm and Sbal-Sbal increased by (0.36 +/- 1.33) mm in the control group. There was significant difference between two groups.",
            "output": [
                "Do [ Comparative analysis of two surgical techniques for controlling nasal width after Le Fort I osteotomy ]?"
            ]
        },
        {
            "id": "task847-db7caee4b8194e5289d4f97f6f3fd9b1",
            "input": "\u00b9\u00b2\u00b3I-FP-CIT (DaTSCAN) SPECT studies of the nigrostriatal pathway are a valuable tool in the diagnosis of movement disorders. However some scans are reported as equivocal with potential adverse consequences. We investigated whether the use of quantification of tracer uptake within the striatum can be used to reduce the number of equivocal reports.', 'BRASS software (Hermes, Sweden) was used to quantify striatal tracer uptake in DaTSCAN studies of patients referred to our institution. Scans were quantified and numerical limits were determined to distinguish between normal and abnormal scans. Scans were then re-reported both with, and without, the use of quantification. Number of equivocal reports and accuracy of reporting between the two types of reporting were compared.', 'Scan reporting using quantification led to a significant reduction in the number of equivocal reports with no significant change in reporting accuracy.",
            "output": [
                "Does automated quantification with BRASS reduce equivocal reporting of DaTSCAN ( 123I-FP-CIT ) SPECT studies?"
            ]
        },
        {
            "id": "task847-bf71ec4793d641b3b960e3962a50d858",
            "input": "Induced sputum analyses are widely utilized to evaluate airway inflammation in asthmatics. However, the values have not been examined in Korean adults.', 'The purpose of this study is to determine reference ranges for induced sputum eosinophils and their influencing factors in Korean adults.', 'A total of 208 healthy nonasthmatic adults were recruited. Sputum induction and processing followed the international standard protocols.', 'Adequate sputum samples were successfully collected from 81 subjects (38.9%). The upper 90 percentile for sputum eosinophil was calculated as 3.5%. The median value of eosinophil count percentage was significantly higher in subjects with atopy than those without atopy (median, 1.6%; range, 0-11.0% vs. median, 0%; range 0-3.6%, p=0.030). However, no significant correlations were found with age, gender, body mass index, smoking status, blood eosinophil, or fractional exhaled nitric oxide levels.",
            "output": [
                "Does reference range for induced sputum eosinophil counts in Korean adult population?"
            ]
        },
        {
            "id": "task847-e20c605cc7704acc8880e24bea3059d8",
            "input": "Retrospective analysis of prospectively collected, nonrandomized radiographical data.', 'To examine the relationship between the presence of preoperative metabolically active facet arthropathy (FA) and the amount of indirect foraminal decompression gained after extreme lateral interbody fusion (XLIF).', 'Although evidence of significant radiographical indirect decompression after XLIF has been shown, the relationship between the extent of indirect decompression and the presence of potentially attenuating, FA is yet to be studied.', 'A prospective database of consecutive patients undergoing XLIF was retrospectively analyzed. Posterior disc height, foraminal height, and cross-sectional foraminal area were measured on computed tomographic scans obtained preoperatively and 2 days postoperatively. The selected radiographical parameters were examined with respect to the presence of FA based on preoperative computed tomographic and bone scans.', 'Fifty-two consecutive patients underwent 79 levels of XLIF without direct decompression. Average age was 66.4 years and 34 (65.4%) were females. Surgery resulted in significant increases in posterior disc height 3.0 to 5.7 mm (89.0% increase), P<0.0001; foraminal height 1.4 to 1.7 cm (38.0% increase), P<0.0001; and foraminal area 1.1 to 1.4 cm (45.1% increase), P<0.0001. These increases were independent of the presence of metabolically active arthropathy.",
            "output": [
                "Is indirect foraminal decompression independent of metabolically active facet arthropathy in extreme lateral interbody fusion?"
            ]
        },
        {
            "id": "task847-784abe6c79914ae4b0b97d2737395199",
            "input": "We compared the length of costal cartilage and rib between patients with symmetric pectus carinatum and controls without anterior chest wall protrusion, using a 3-dimensional (3D) computed tomography (CT) to evaluate whether the overgrowth of costal cartilage exists in patients with pectus carinatum.', 'Twenty-six patients with symmetric pectus carinatum and matched twenty-six controls without chest wall protrusion were enrolled. We measured the full lengths of the 4th-6th ribs and costal cartilages using 3-D volume rendering CT images and the curved multiplanar reformatted (MPR) techniques. The lengths of ribs and costal cartilages, the summation of rib and costal cartilage lengths, and the costal index [length of cartilage/length of rib * 100 (%)] were compared between the patients group and the control group at 4th-6th levels.', 'The lengths of costal cartilage in patient group were significantly longer than those of control group at 4th, 5th and 6th rib level. The lengths of ribs in patient group were significantly shorter than those of control group at 4th, 5th and 6th rib level. The summations of rib and costal cartilage lengths were not longer in patients group than in control group. The costal indices were significantly larger in patients group than in control groups at 4th, 5th and 6th rib level.",
            "output": [
                "Does the etiology of pectus carinatum involve overgrowth of costal cartilage and undergrowth of ribs?"
            ]
        },
        {
            "id": "task847-25f030fe6e3e4c7a814c453ff2ae7cba",
            "input": "Consumption of lycopene through tomato products has been suggested to reduce the risk of prostate cancer. Cellular adhesion and migration are important features of cancer progression and therefore a potential target for cancer interception. In the present study we have examined the in vitro effect of lycopene on these processes.', 'Prostate cancer cell lines PC3, DU145 and immortalised normal prostate cell line PNT-2 were used. The adhesion assay consisted of seeding pre-treated cells onto Matrigel\u2122, gently removing non-adherent cells and quantitating the adherent fraction using WST-1. Migratory potential was assessed using ibidi\u2122 migration chamber inserts, in which a cell-free zone between two confluent areas was allowed to populate over time and the migration measured.', '24 hour incubation of prostate cell lines with 1.15\u00b5mol/l lycopene showed a 40% reduction of cellular motility in case of PC3 cells, 58% in DU145 cells and no effect was observed for PNT2 cells. A dose related inhibition of cell adhesion to a basement membrane in the form of Matrigel\u2122 was observed in all three cell lines and it reached statistical significance for PC3 and PNT2 cells at lycopene concentrations \u22651.15\u00b5mol/l. However, in case of DU145, only a concentration of 2.3\u00b5mol/l showed a significant reduction.",
            "output": [
                "Does lycopene treatment of prostate cancer cell lines inhibit adhesion and migration properties of the cells?"
            ]
        },
        {
            "id": "task847-af343145c53e4b24ad534166cce50b6c",
            "input": "Dacts are multi-domain adaptor proteins. They have been implicated in Wnt and Tgf\u03b2 signaling and serve as a nodal point in regulating many cellular activities. Dact genes have so far only been identified in bony vertebrates. Also, the number of Dact genes in a given species, the number and roles of protein motifs and functional domains, and the overlap of gene expression domains are all not clear. To address these problems, we have taken an evolutionary approach, screening for Dact genes in the animal kingdom and establishing their phylogeny and the synteny of Dact loci. Furthermore, we performed a deep analysis of the various Dact protein motifs and compared the expression patterns of different Dacts.', 'Our study identified previously not recognized dact genes and showed that they evolved late in the deuterostome lineage. In gnathostomes, four Dact genes were generated by the two rounds of whole genome duplication in the vertebrate ancestor, with Dact1/3 and Dact2/4, respectively, arising from the two genes generated during the first genome duplication. In actinopterygians, a further dact4r gene arose from retrotranscription. The third genome duplication in the teleost ancestor, and subsequent gene loss in most gnathostome lineages left extant species with a subset of Dact genes. The distribution of functional domains suggests that the ancestral Dact function lied with Wnt signaling, and a role in Tgf\u03b2 signaling may have emerged with the Dact2/4 ancestor. Motif reduction, in particular in Dact4, suggests that this protein may counteract the function of the other Dacts. Dact genes were expressed in both distinct and overlapping domains, suggesting possible combinatorial function.",
            "output": [
                "Are dact genes chordate specific regulators at the intersection of Wnt and Tgf-\u03b2 signaling pathways?"
            ]
        },
        {
            "id": "task847-cc4788b97e00415291ac2e41a8b28983",
            "input": "Cerebral white matter lesions (WMLs) predict long-term survival of conservatively treated acute stroke patients with etiology other than carotid stenosis. In carotid endarterectomy patients, WMLs are associated with severe carotid stenosis and unstable plaques, with the risk of perioperative complications and with increased 30-day perioperative risk of death. However, no data exist on their effect on postoperative long-term survival, a factor important when considering the net benefit from carotid endarterectomy. Whether this effect is independent of classical risk factors and indications for surgery is not known either. We hypothesized that WMLs could be evaluated from preoperative routine computed tomography (CT) scans and are predictors of postoperative survival, independent of classical cardiovascular risk factors, indication category and degree of carotid stenosis.', \"A total of 353 of 481 (73.4%) consecutive patients subjected to carotid endarterectomy due to different indications, i.e. asymptomatic stenosis (n = 28, 7.9%), amaurosis fugax (n = 52, 14.7%), transient ischemic attack (n = 135, 38.2%) or ischemic stroke (n = 138, 39.1%), from prospective vascular registries during the years 2001-2010 with digital preoperative CT scans, were included in the study. WMLs were rated by a radiologist (Wahlund criteria) in a blinded fashion. Internal carotid artery (ICA) stenoses were angiographically graded (<50, 50-69, 70-99 and 100%). Odds ratios (ORs) and hazard ratios (HRs) are reported (ORs and HRs \u22641 indicate a beneficial effect). The median follow-up time was 67 months (interquartile range 45.5, range 0-129 months). Spearman's rho was used to estimate intraobserver agreement. Binary logistic regression was performed to analyze the association of risk factors with WMLs. Cox regression proportional hazards analysis was used to study the effect of different factors on survival.\", \"WML severity could be assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p < 0.0001). Only age (OR 1.10, 95% CI 1.06-1.15; p < 0.0001 per year), degree of ipsilateral ICA stenosis (OR 2.22, 95% CI 1.08-4.55; p < 0.05 per stenosis grade) and indication category (OR 1.63, 95% CI 1.19-2.24; p < 0.01 per category) remained independently associated with WMLs. Age (HR 1.04, 95% CI 1.01-1.08; p < 0.05 per year), diabetes (HR 1.59, 95% CI 1.01-2.49; p < 0.05), peripheral arterial disease (HR 2.47, 95% CI 1.46-4.15; p < 0.01), degree of ipsilateral ICA stenosis (HR 2.56, 95% CI 1.12-5.87; p < 0.05 per stenosis grade) and WMLs (HR 3.83, 95% CI 1.17-12.5; p < 0.05) remained independently associated with increased long-term mortality.",
            "output": [
                "Are preoperative white matter lesions independent predictors of long-term survival after internal carotid endarterectomy?"
            ]
        },
        {
            "id": "task847-d41beb88ec964dcaa9edee0e77cc6c82",
            "input": "Arginine deiminase (ADI) and L-arginine (L-Arg) can act as anti-tumor agents in-vitro and in-vivo. However, the mechanism of ADI and L-Arg as anti-tumor agents has not been clearly shown.', 'With the goal of understanding the role of ADI and L-Arg in inhibition of cell growth, we used the Ramos human lymphoma cell line, which is known to be ADI-sensitive, and observed the p53 and NF-\u03baBp65 protein expression after ADI and arginine treatment. After determining an optimal experimental ADI concentration (0.01 U/ml), we studied the effects of ADI treatment, when combined with different concentrations of L-arginine (control, ADI only, ADI with 10 mM/ml Arg, ADI with 30 mM/ml Arg, and ADI with 50 mM/ml Arg). An MTT assay was used to assess cell survival after treatment, Western blot analysis to determine the levels of the NF-\u03baBp65, p53 and NO mediators and nitric oxide assays were used to determine nitrite levels.",
            "output": [
                "Does l-arginine enhance arginine deiminase induced human lymphoma cell growth inhibition through NF-kBp65 and p53 expression in vitro?"
            ]
        },
        {
            "id": "task847-caf29a89b1e14f2a9dd042c39a6af356",
            "input": "We tested for the presence of erythropoietin receptor (Epo-R) in human skeletal muscle and alterations in gene expression after prolonged use of an erythropoiesis-stimulating agent (ESA).', 'Nine healthy men were treated with ESA for 10 weeks (darbepoietin alfa). Muscle biopsies were collected before and after treatment. Alterations in gene expression were evaluated by gene array. Western blot and PCR analysis were used to test for Epo-R presence in human skeletal muscle.', 'Very low Epo-R mRNA levels were found, but a new and sensitive antibody did not identify Epo-R protein in human skeletal muscle. The between-subject variation in skeletal muscle gene expression was greater than that observed in response to prolonged ESA treatment.",
            "output": [
                "Does prolonged erythropoietin treatment impact gene expression in human skeletal muscle?"
            ]
        },
        {
            "id": "task847-a17f6cdb062a499fb209ff8736df1b38",
            "input": "Prostate cancer is the second most common form of cancer in males, affecting one in eight men by the time they reach the age of 70 years. Current diagnostic tests for prostate cancer have significant problems with both false negatives and false positives, necessitating the search for new molecular markers. A recent investigation of endosomal and lysosomal proteins revealed that the critical process of endosomal biogenesis might be altered in prostate cancer. Here, a panel of endosomal markers was evaluated in prostate cancer and nonmalignant cells and a significant increase in gene and protein expression was found for early, but not late endosomal proteins. There was also a differential distribution of early endosomes, and altered endosomal traffic and signaling of the transferrin receptors (TFRC and TFR2) in prostate cancer cells. These findings support the concept that endosome biogenesis and function are altered in prostate cancer. Microarray analysis of a clinical cohort confirmed the altered endosomal gene expression observed in cultured prostate cancer cells. Furthermore, in prostate cancer patient tissue specimens, the early endosomal marker and adaptor protein APPL1 showed consistently altered basement membrane histology in the vicinity of tumors and concentrated staining within tumor masses. These novel observations on altered early endosome biogenesis provide a new avenue for prostate cancer biomarker investigation and suggest new methods for the early diagnosis and accurate prognosis of prostate cancer.",
            "output": [
                "Does altered endosome biogenesis in prostate cancer have biomarker potential?"
            ]
        },
        {
            "id": "task847-0b97e2aaf1b04790a65f4579df8cfc53",
            "input": "Bicuspid aortic valve (BAV) is the most common congenital cardiovascular malformation. Although highly heritable, few causal variants have been identified. The purpose of this study was to identify genetic variants underlying BAV by whole exome sequencing a multiplex BAV kindred.', 'Whole exome sequencing was performed on 17 individuals from a single family (BAV=3; other cardiovascular malformation, 3). Postvariant calling error control metrics were established after examining the relationship between Mendelian inheritance error rate and coverage, quality score, and call rate. To determine the most effective approach to identifying susceptibility variants from among 54 674 variants passing error control metrics, we evaluated 3 variant selection strategies frequently used in whole exome sequencing studies plus extended family linkage. No putative rare, high-effect variants were identified in all affected but no unaffected individuals. Eight high-effect variants were identified by \u22652 of the commonly used selection strategies; however, these were either common in the general population (>10%) or present in the majority of the unaffected family members. However, using extended family linkage, 3 synonymous variants were identified; all 3 variants were identified by at least one other strategy.",
            "output": [
                "Does whole exome sequencing for familial bicuspid aortic valve identify putative variants?"
            ]
        },
        {
            "id": "task847-3d45614fc0a44733aaf3452c614764e4",
            "input": "Crowdsourcing dietary ratings for food photographs, which uses the input of several users to provide feedback, has potential to assist with dietary self-monitoring.', \"This study assessed how closely crowdsourced ratings of foods and beverages contained in 450 pictures from the Eatery mobile app as rated by peer users (fellow Eatery app users) (n = 5006 peers, mean 18.4 peer ratings/photo) using a simple 'healthiness' scale were related to the ratings of the same pictures by trained observers (raters). In addition, the foods and beverages present in each picture were categorized and the impact on the peer rating scale by food/beverage category was examined. Raters were trained to provide a 'healthiness' score using criteria from the 2010 US Dietary Guidelines.\", \"The average of all three raters' scores was highly correlated with the peer healthiness score for all photos (r = 0.88, p<0.001). Using a multivariate linear model (R(2) = 0.73) to examine the association of peer healthiness scores with foods and beverages present in photos, peer ratings were in the hypothesized direction for both foods/beverages to increase and ones to limit. Photos with fruit, vegetables, whole grains, and legumes, nuts, and seeds (borderline at p = 0.06) were all associated with higher peer healthiness scores, and processed foods (borderline at p = 0.06), food from fast food restaurants, refined grains, red meat, cheese, savory snacks, sweets/desserts, and sugar-sweetened beverages were associated with lower peer healthiness scores.",
            "output": [
                "Are the use of crowdsourcing for dietary self-monitoring : crowdsourced ratings of food pictures comparable to ratings by trained observers?"
            ]
        },
        {
            "id": "task847-4811421cf84f4f57a5cc3d087317e47d",
            "input": "To determine the efficacy of Sustained Natural Apophyseal Glides (SNAGs) with and without Isometric Exercise Training Program (IETP) in Non-specific Neck Pain (NSNP) Methods: This randomized control trial of one year duration was conducted at out-patient department of Physiotherapy and Rehabilitation, Khyber Teaching Hospital (KTH) Peshawar, Pakistan from July 2012 to June 2013. The sample of 102 patients of NSNP were randomly selected through simple random sampling technique, and placed into two groups. The SNAGs manual physical therapy technique with IETP was applied on 51 patients in group A and SNAGs manual physical therapy techniques was applied alone on 51 patients in group B. The duration of intervention was 6 weeks, at 4 times per week. The Neck Disability Index (NDI) and Visual Analog Scale (VAS) for neck pain were assessment tools used for all patients before and after 6 weeks of physical therapy intervention. All the patients were assessed through NDI and VAS before intervention and at the completion of 6 weeks program. The data of all 102 was analyzed by SPSS-20 and statistical test was applied at 95% level of significance determine the efficacy of both the treatments interventions and compare with each other.', 'The patients in group A, treated with SNAGs and followed by IETP for 6 weeks, demonstrated more improvement in pain and physical activity as assessed by VAS (p=0.013) and NDI (p=0.003), as compared to the patients treated with SNAGS alone, as pain and function assessed by VAS (p=0.047) and NDI (p=0.164). In group A the NDI score improved from 40 to 15 and VAS from 7 to 4, while in group B the NDI score improved from 42 to 30 and VAS from 7 to 4.",
            "output": [
                "Does the efficacy of Sustained Natural Apophyseal glide with and without Isometric Exercise Training in Non-specific Neck Pain?"
            ]
        },
        {
            "id": "task847-2d7f3afd8f8b48119ed861be41058903",
            "input": "Subcortical band heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats.', 'Rats with SBH (Dcx-KD rats) were generated by knocking down the Dcx gene using shRNA vectors transfected into neocortical progenitors of rat embryos. Origin, spatial extent, and laminar profile of bicuculline-induced interictal-like activity on neocortical slices were analyzed by using extracellular recordings from 60-channel microelectrode arrays. Susceptibility to pentylenetetrazole-induced seizures was assessed by electrocorticography in head-restrained nonanesthetized rats.', 'We show that the band heterotopia does not constitute a primary origin for interictal-like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Furthermore, we report that most interictal-like discharges originating in the overlying cortex secondarily propagate to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx-KD rats to display seizures.",
            "output": [
                "Is normotopic cortex the major contributor to epilepsy in experimental double cortex?"
            ]
        },
        {
            "id": "task847-b82466a0df4d40a799ca58f93f9aa684",
            "input": "The study was conducted to simultaneously investigate the mediating effects of parental control and adolescents' self-control on the relationship between adolescents' negative emotions and emotional eating, and to determine pathways with the greatest effect among these variables.\", 'Negative emotions, emotional eating, parental control, and self-control were investigated in 594 high school students (average age=16.70, SD=1.09) in Changsha City, China.', \"High levels of negative emotions and parental control and low levels of self-control were strongly related to high levels of emotional eating in adolescents. In addition to the direct relationship between negative emotions and emotional eating, there was a mediating effect observed through low self-control and high parental control. The mediational effect of parental control was non-significant in adolescent boys. Furthermore, negative emotions related to emotional eating through the effect of parental control on adolescents' self-control. The degree to which both mediators explained the relationship between negative emotions and emotional eating ranged from 52.6% to 66.8%, and self-control had a stronger mediational effect than did parental control.",
            "output": [
                "Do self-control and parental control mediate the relationship between negative emotions and emotional eating among adolescents?"
            ]
        },
        {
            "id": "task847-e038321301a64098a70d2c5dd0676843",
            "input": "Exclusion of macroprolactinaemia, a well-recognised interference, as the cause of hyperprolactinaemia is essential to avoid potential misdiagnosis and mismanagement of patients. We have derived gender-specific serum total and post-polyethylene glycol (PEG) precipitation monomeric reference ranges for the recently re-standardised Abbott Architect prolactin assay.', \"Prolactin was measured in serum samples obtained from males (n=49) and females (n=52) using the current Abbott Architect immunoassay pre- and post-PEG precipitation. Gender-specific reference ranges were derived for total and monomeric (post-PEG) prolactin. Routine patients' samples (n=175) with a serum total prolactin >700 mIU/L were screened for macroprolactinaemia to assess classification compared with our previous post-PEG precipitation percentage recovery-based approach.\", \"Reference ranges for serum total prolactin were 58-419 mIU/L (male) and 63-561 mIU/L (female). Male and female monomeric prolactin reference ranges were 32-309 mIU/L and 39-422 mIU/L, respectively. Mean (SD) post-PEG percentage recovery of the IS 84/500 prolactin standard was 80 (2.3)%. Of 175 patients' samples screened for macroprolactinaemia, 149 had monomeric prolactin concentrations (median monomeric prolactin=1035 mIU/L; median recovery=83%) above the gender-specific reference range. Monomeric prolactin concentrations (median monomeric prolactin=162 mIU/L; median recovery=20%) in the remaining 26 were within the reference ranges. One patient classified as macroprolactin positive and another classified as macroprolactin negative would not have been identified as such using the previous recovery-based approach.",
            "output": [
                "Does reference range for serum total and monomeric prolactin for the current generation Abbott Architect assay?"
            ]
        },
        {
            "id": "task847-4534c176eb41443cadbed4b233b71833",
            "input": "Attentional and executive dysfunctions are associated with falls in community-dwelling elderly individuals and patients with PD. Frontal cognitive dysfunction and falls are frequent symptoms of PSP. We studied to identify the cognitive domains associated with recurrent falls in patients with PSP.', 'We performed a battery of neuropsychological tests in 59 individuals with probable PSP. We categorized patients into infrequent fall (\u2264one fall during the last 12 months, n=29) or recurrent fall (\u2265two falls during the last 12 months, n=30) groups.', 'UPDRS subscores for axial deficits were significantly higher in the recurrent fall group than the infrequent fall group, but there were no significant differences in UPDRS total motor scores or subscores for bradykinesia, rigidity, and tremor. There was no difference between groups in MMSE scores. ANCOVA with adjustment for confounding factors showed that, recurrent falls were associated with abnormalities in alternating hand movement, alternating square and triangle, RCFT copying task, and ideomotor apraxia. Group difference of abnormalities in Stroop test was marginal (p=0.054). However, there were no group differences in the frequency of abnormalities in forward or backward digit span, motor impersistence, fist-edge-palm, contrast programming, go-no-go, Luria loop drawing, or Controlled Oral Word Association Tests. Recurrent falls were not associated with memory or language dysfunction.",
            "output": [
                "Does cognitive dysfunction associated with fall in progressive supranuclear palsy?"
            ]
        },
        {
            "id": "task847-0e86d5ca45a8407fba04fdc049b092f6",
            "input": "Arthritis pain is reported as one of the most common reasons for persons using medical herbal cannabis in North America. \"Severe arthritis\" is the condition justifying legal use of cannabis in over half of all authorizations in Canada, where cannabis remains a controlled substance. As champions for the care of persons with arthritis, rheumatologists must be knowledgeable of treatment modalities both traditional and non-traditional, used by their patients. As study of cannabinoid molecules in medicine is recent, we have examined the confidence in the knowledge of cannabinoids expressed by Canadian rheumatologists.', 'The confidence of rheumatologists in their knowledge of cannabinoid molecules and mechanisms relevant to rheumatology, and their ability to advise patients about cannabinoid treatments was recorded by an online questionnaire circulated via email to the entire Canadian Rheumatology Association membership.', 'Over three quarters of the 128 respondents lacked confidence in their knowledge of cannabinoid molecules. While 45% of respondents believed there was no current role for cannabinoids in rheumatology patient care, only 25% supported any use of herbal cannabis. With 70% never having previously prescribed or recommended any cannabinoid treatment, uncertainty regarding good prescribing practices was prevalent. Concerns about risks of cannabis use were in line with the current literature.",
            "output": [
                "Do rheumatologists lack confidence in their knowledge of cannabinoids pertaining to the management of rheumatic complaints?"
            ]
        },
        {
            "id": "task847-4416253a45544b02b3c6620c7505c7ec",
            "input": "Cervical cancer continues to threaten women's health worldwide, and the incidence of cervical adenocarcinoma (AD) is rising in the developed countries. Previously, we showed that glucose-regulated protein 58 (Grp58) served as an independent factor predictive of poor prognosis of patients with cervical AD. However, the molecular mechanism underlying the involvement of Grp58 in cervical carcinogenesis is currently unknown.\", 'DNA microarray and enrichment analysis were used to identify the pathways disrupted by knockdown of Grp58 expression.', 'Among the pathway identified, the WNT signaling pathway was one of those that were significantly associated with knockdown of Grp58 expression in HeLa cells. Our experiments showed that \u03b2-catenin, a critical effector of WNT signaling, was stabilized thereby accumulated in stable Grp58 knockdown cells. Membrane localization of \u03b2-catenin was observed in Grp58 knockdown, but not control cells. Using a transwell assay, we found that accumulated \u03b2-catenin induced by Grp58 knockdown or lithium chloride treatment inhibited the migration ability of HeLa cells. Furthermore, an inverse expression pattern of Grp58 and \u03b2-catenin was observed in cervical tissues.",
            "output": [
                "Does glucose-regulated protein 58 modulate \u03b2-catenin protein stability in a cervical adenocarcinoma cell line?"
            ]
        },
        {
            "id": "task847-5ee2eb11ded84465b2ad63abec7b04af",
            "input": "Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD.', 'Cross-sectional comparison of fMRI signal during performance of an emotion processing task.', 'Outpatient university setting.', 'One hundred adults recruited by MDD status, gender, and age.', 'Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks.', 'Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts.",
            "output": [
                "Do age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder?"
            ]
        },
        {
            "id": "task847-24ccd77606784831b210b3eef4c5f24a",
            "input": "There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments. This randomised controlled trial aimed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy.', '150 out of 179 eligible patients, aged 45 to 64 (mean:54\\xa0\u00b1\\xa05), symptom duration more than 3 months and standing X-ray with Ahlb\u00e4ck grade 0, were randomised to: (1) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme (non-surgery group); or (2) the same as (1) plus, within 4 weeks of inclusion, knee arthroscopy for resection of any significant meniscal injuries (surgery group). The primary outcome was change in pain at 12 months, assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOSPAIN).', 'In the Intention-To-Treat analysis, pain at 12 months was significantly lower in the surgery than in the non-surgery group. The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group (between-group difference was 10.6 points of change; 95% CI: 3.4 to 17.7, P\\xa0=\\xa00.004). The As-Treated analysis results were consistent with the Intention-To-Treat analysis results.",
            "output": [
                "Is knee arthroscopic surgery beneficial to middle-aged patients with meniscal symptoms : a prospective , randomised , single-blinded study?"
            ]
        },
        {
            "id": "task847-0932aa1afb5649b78bf550cf0bc1e3f3",
            "input": "To evaluate pain behavior and structural damage in mice subjected to either meniscal transection or removal.', 'Mice (10/group) were subjected to transection of the medial collateral and anterior cruciate ligaments (ACLT/MCLT) followed by either transection (meniscotomy) or removal (meniscectomy) of the medial meniscus. A control group was subjected only to transection of the ligaments. Pain was assessed using the electronic pressure-meter paw test. Cell influx, measured in joint exudates, and joint histopathology were assessed after 49 days. Four other groups subjected to meniscotomy received indomethacin, the inducible nitric oxide synthase (iNOS) inhibitor 1400W, morphine or the vehicles.', 'Both meniscotomy and meniscectomy groups displayed persistent and significant increase in pain behavior as compared to controls, being significantly more severe in the former. Cell influx was more intense in the meniscotomy as compared to the meniscectomy group. Structural damage at the tibia, but not at the femur, was also more severe in the meniscotomy group. Indomethacin and 1400W partially but significantly reduced pain whereas morphine abrogated pain behavior in meniscotomized mice.",
            "output": [
                "Does meniscal transection rather than excision increase pain behavior and structural damage in experimental osteoarthritis in mice?"
            ]
        },
        {
            "id": "task847-8704c130e59c439ca231d79822ec52eb",
            "input": "5-year survival for melanoma metastasis to regional lymph nodes (American Joint Committee on Cancer stage III) is <50%. Knowledge of outcomes following therapeutic lymphadenectomy for stage III melanoma related to BRAF status may guide adjuvant use of BRAF/MEK inhibitors along with established and future therapies.', 'To determine patterns of melanoma recurrence and survival following therapeutic lymph node dissection (TLND) associated with oncogenic mutations.', 'DNA was obtained from patients who underwent TLND and had \u2a7e2 positive nodes, largest node >3cm or extracapsular invasion. Mutations were detected using an extended Sequenom MelaCARTA panel.', 'Mutations were most commonly detected in BRAF (57/124 [46%] patients) and NRAS (26/124 [21%] patients). Patients with BRAF mutations had higher 3-year recurrence rate (77%) versus 54% for BRAF wild-type patients (hazard ratio (HR) 1.8, p=0.008). The only prognostically significant mutations occurred in BRAF: median recurrence-free (RFS) and disease-specific survival (DSS) for BRAF mutation patients was 7 months and 16 months, versus 19 months and not reached for BRAF wild-type patients, respectively. Multivariate analysis identified BRAF mutant status and number of positive lymph nodes as the only independent prognostic factors for RFS and DSS.",
            "output": [
                "Is bRAF mutation status an independent prognostic factor for resected stage IIIB and IIIC melanoma : implications for melanoma staging and adjuvant therapy?"
            ]
        },
        {
            "id": "task847-1c708a56fea84985b1b892d60642063d",
            "input": "Testicular germ cell tumours are the most common malignancies in young males. Molecular biology studies of these tumours are often contradictory. Two histological groups, seminoma and non-seminoma, differ both morphologically and in malignant behaviour. Although a common cytogenetic feature is seen, namely the amplification of the 12p chromosomal region, the development mechanisms of less aggressive seminomas and more aggressive non-seminomas are unknown.', 'Occurrence of structural genetic alterations was analyzed in 18 seminomas and 22 non-seminomas for genes involved in the malignant tumour phenotype: cadherin 1, Type 1, E-cadherin (Epithelial), CDH1; adenomatous polyposis coli, APC; NME/NM23 nucleoside diphosphate kinase 1, NME1; tumour protein P53, TP53; cyclin-dependent kinase inhibitor 2A, CDKN2A; retinoblastoma 1, RB1; RAD51 recombinase, RAD51; mutS homolog 2, MSH2; MutL homolog 1, MLH1; breast cancer 1, early onset, BRCA1; BCL2-Associated X Protein, BAX; ATP-Binding Cassette, Sub-Family G (WHITE), Member 2, ABCG2. Genetic alterations, loss of heterozygosity and microsatellite instability, were analyzed using restriction fragment or microsatellite repeat length polymorphisms.', 'A difference in genetic alteration occurrence between seminomas and non-seminomas was observed.",
            "output": [
                "Do histological groups of human postpubertal testicular germ cell tumours harbour different genetic alterations?"
            ]
        },
        {
            "id": "task847-14b7cddb7eb04924ab532379522bc35e",
            "input": "SOX18 is a transcription factor known to be involved in blood and lymphatic vessel, hair follicle development, and wound healing processes. In addition, it has been reported that SOX18 may influence cancer growth. The role of SOX18 expression in ovarian cancer (OC) has not been determined.', 'SOX18 expression was assessed in 85 OC cases using immunohistochemical methods and in ovarian cancer cell lines on the mRNA and protein level.', 'SOX18 was expressed in cancer cell nuclei as well as the cytoplasm. Higher nuclear SOX18 expression was associated with presence of residual disease following surgical treatment (p=0.0158) and advanced disease stage (p=0.0056). Univariate survival analysis revealed that high SOX18 (p=0.0125) expression, presence of residual disease (p<0.0001) and advanced disease stage (p<0.0324) predicted poor patient outcome.",
            "output": [
                "Does sOX18 expression predict response to platinum-based chemotherapy in ovarian cancer?"
            ]
        },
        {
            "id": "task847-ed05a6dc04264ae8bcb67d58a74ac29a",
            "input": "Arsenic trioxide (ATO) strongly induces apoptosis and differentiation in acute promyelocytic leukemia, and induces cell cycle arrest in most solid tumors. Although many signaling pathways are involved in its antitumor mechanism, a detailed investigation of the transforming growth factor beta-bone morphogenetic protein signaling pathway has not been performed.', 'A microarray containing 113 genes associated with the pathway was used to screen important molecules that participate in the antitumor effects of ATO. The expression levels of the inhibitors of DNA binding-2 (ID2) in 4 different types of cancer cells were determined by quantitative reverse transcription PCR and Western blotting. Human esophageal squamous cell carcinoma cell line Eca109 and pancreatic carcinoma cell line BxPC3 cells were transfected with siRNAs targeting ID2 and scrambled control siRNA. Cell proliferation was evaluated by methyl thiazolyl tetrazolium assay.', 'Eighteen upregulated and 12 downregulated genes were identified. After verification at the transcriptional and translational levels in 4 different cancer cells, ID2 was identified as an ATO antitumor-associated protein. In addition, specific silencing of ID2 could enhance ATO-induced cell proliferation inhibition in cancer cells.",
            "output": [
                "Does upregulation of ID2 antagonize arsenic trioxide-induced antitumor effects in cancer cells?"
            ]
        },
        {
            "id": "task847-65c52e806fe849b6a7516d447087f8a0",
            "input": "During early brain development, the organisation of neural progenitors into a neuroepithelial sheet maintains tissue integrity during growth. Neuroepithelial cohesion and patterning is essential for orderly proliferation and neural fate specification. Neuroepithelia are regionalised by the expression of transcription factors and signalling molecules, resulting in the formation of distinct developmental, and ultimately functional, domains.', 'We have discovered that the Six3/6 family orthologue Optix is an essential regulator of neuroepithelial maintenance and patterning in the Drosophila brain. Six3 and Six6 are required for mammalian eye and forebrain development, and mutations in humans are associated with severe eye and brain malformation. In Drosophila, Optix is expressed in a sharply defined region of the larval optic lobe, and its expression is reciprocal to that of the transcription factor Vsx1. Optix gain- and loss-of-function affects neuroepithelial adhesion, integrity and polarity. We find restricted cell lineage boundaries that correspond to transcription factor expression domains.",
            "output": [
                "Does optix define a neuroepithelial compartment in the optic lobe of the Drosophila brain?"
            ]
        },
        {
            "id": "task847-f9c92733ca57445ebd54b24f210f3e18",
            "input": "The airways of people with cystic fibrosis (CF) are chronically infected with a variety of bacterial species. Although routine culture methods are usually used to diagnose these infections, culture-independent, DNA-based methods have identified many bacterial species in CF respiratory secretions that are not routinely cultured. Many prior culture-independent studies focused either on microbiota in explanted CF lungs, reflecting end-stage disease, or those in oropharyngeal swabs, which likely sample areas in addition to the lower airways. Therefore, it was unknown whether the lower airways of children with CF, well before end-stage but with symptomatic lung disease, truly contained diverse microbiota.', 'To define the microbiota in the diseased lung tissue of a child who underwent lobectomy for severe, localized CF lung disease.', \"After pathologic examination verified that this child's lung tissue reflected CF lung disease, we used bacterial ribosomal RNA gene pyrosequencing and computational phylogenetic analysis to identify the microbiota in serial sections of the tissue.\", 'This analysis identified diverse, and anatomically heterogeneous, bacterial populations in the lung tissue that contained both culturable and nonculturable species, including abundant Haemophilus, Ralstonia, and Propionibacterium species. Routine clinical cultures identified only Staphylococcus aureus, which represented only a small fraction of the microbiota found by sequencing. Microbiota analysis of an intraoperative oropharyngeal swab identified predominantly Streptococcus species. The oropharyngeal findings therefore represented the lung tissue microbiota poorly, in agreement with findings from earlier studies of oropharyngeal swabs in end-stage disease.",
            "output": [
                "Does directly sampling the lung of a young child with cystic fibrosis reveal diverse microbiota?"
            ]
        },
        {
            "id": "task847-a5451e3df46d4744b86da791faae7cae",
            "input": "To assess the association between self-perceived exercise exertion before bedtime and objectively measured sleep.', 'Fifty-two regularly exercising young adults (mean age, 19.70\\u2009years; 54% females) underwent sleep electroencephalographic recordings 1.5\\u2009h after completing moderate to vigorous exercise in the evening. Before sleeping, participants answered questions regarding degree of exertion of the exercise undertaken.', 'Greater self-perceived exertion before bedtime was associated with higher objectively assessed sleep efficiency (r\\u2009=\\u20090.69, P\\u2009<0.001); self-perceived exertion explained 48% of the variance in sleep efficiency (R2\\u2009=\\u20090.48). Moreover, high self-perceived exercise exertion was associated with more deep sleep, shortened sleep onset time, fewer awakenings after sleep onset, and shorter wake duration after sleep onset. Multiple linear regression analysis showed that objective sleep efficiency was predicted by increased exercise exertion, shortened sleep onset time, increased deep sleep, and decreased light sleep.",
            "output": [
                "Is high self-perceived exercise exertion before bedtime associated with greater objectively assessed sleep efficiency?"
            ]
        },
        {
            "id": "task847-483156c0d38f4eff8b492d3057a725a7",
            "input": "DNA methylation is an important biological form of epigenetic modification, playing key roles in plant development and environmental responses.', 'In this study, we examined single-base resolution methylomes of Populus under control and drought stress conditions using high-throughput bisulfite sequencing for the first time. Our data showed methylation levels of methylated cytosines, upstream 2 kp, downstream 2kb, and repeatitive sequences significantly increased after drought treatment in Populus. Interestingly, methylation in 100 bp upstream of the transcriptional start site (TSS) repressed gene expression, while methylations in 100-2000 bp upstream of TSS and within the gene body were positively associated with gene expression. Integrated with the transcriptomic data, we found that all cis-splicing genes were non-methylated, suggesting that DNA methylation may not associate with cis-splicing. However, our results showed that 80% of trans-splicing genes were methylated. Moreover, we found 1156 transcription factors (TFs) with reduced methylation and expression levels and 690 TFs with increased methylation and expression levels after drought treatment. These TFs may play important roles in Populus drought stress responses through the changes of DNA methylation.",
            "output": [
                "Do single-base-resolution methylomes of Populus trichocarpa reveal the association between DNA methylation and drought stress?"
            ]
        },
        {
            "id": "task847-2cf82dedfb9d4bf2996322d762b88fd7",
            "input": "Profilins are actin-modulating proteins regulating many intracellular functions based on their multiple and diverse ligand interactions. They have been implicated to play a role in many pathological conditions such as allergies, cardiovascular diseases, muscular atrophy, diabetes, dementia and cancer. Post-translational modifications of profilin 1 can alter its properties and subsequently its function in a cell. In the present study, we identify the importance of phosphorylation of profilin 1 at serine 137 (S137) residue in breast cancer progression.', 'We found elevated profilin 1 (PFN) in human breast cancer tissues when compared to adjacent normal tissues. Overexpression of wild-type profilin 1 (PFN-WT) in breast cancer MCF7 cells made them more migratory, invasive and adherent independent in comparison to empty vector transfected cells. Mutation in serine phosphorylation site (S137) of profilin 1 (PFN-S137A) significantly abrogated these properties. Mutation affecting actin-binding ability (PFN-R74E) of profilin 1 enhanced its tumorigenic function whereas mutation affecting its poly-L-proline binding function (PFN-H133S) alleviated these mechanisms in breast cancer cells. PFN-WT was found to activate matrix metalloproteinases by zymography, MMP2 and MMP9 in presence of PDBu (phorbol 12, 13 dibutyrate, PI3K agonist) to enhance migration and invasion in MCF7 cells while PFN-S137A did not. Phosphorylation increased migration and invasion in other mutants of profilin 1. Nuclear profilin levels also increased in the presence of PDBu.",
            "output": [
                "Is s137 phosphorylation of profilin 1 an important signaling event in breast cancer progression?"
            ]
        },
        {
            "id": "task847-ea73a66b56674f4d87f6940a57168c20",
            "input": "The epigenetic mechanism of tumorigenesis in pancreatic intraductal papillary mucinous neoplasm (IPMN) remains largely unknown. The aim of this study is to examine the role of enhancer of zeste homologue 2 (EZH2) alteration in pancreatic IPMN progression.', 'Fifty-four surgically resected pancreatic IPMN specimens, including a total of 181 lesions (normal duct in 48, adenoma in 50, borderline atypia in 53, carcinoma in situ (CIS) in 19, and invasive carcinoma in 11) were analyzed by immunohistochemical staining (EZH2, Ki-67, p27Kip1). Using paraffin embedded sections, total RNA was successfully extracted from 20 IPMN lesions (borderline IPMN in 9, CIS in 6, invasive carcinoma in 5) and 7 pancreatic normal ducts, and then levels of EZH2 and p27Kip1 mRNA were analyzed by real time PCR.', 'In immunohistochemical analysis, cell proliferative activity revealed by Ki-67 positive nuclei was increased during IPMN progression (normal duct<adenoma<borderline atypia<CIS \u2248 invasive carcinoma). EZH2 expression displayed a similar pattern (normal duct<adenoma<borderline atypia<CIS \u2248 invasive carcinoma) with cell proliferative activity. EZH2 expression in malignant (CIS and invasive carcinoma) IPMNs was significantly higher than that in adenoma and borderline-atypia IPMNs. EZH2 expression level in IPMN lesions was positively correlated with the Ki-67 positive nuclear ratio (p<0.0001). EZH2-positive cells in malignant IPMN did not express p27Kip1. EZH2 mRNA expressions in malignant lesions were significantly higher than those in benign lesions (p<0.0001). In contrast, p27Kip1 mRNA in malignant lesions was significantly decreased compared to those in benign lesion (p<0.05), and there was an inverse correlation between EZH2 and p27Kip1 mRNA levels (p = 0.0109).",
            "output": [
                "Is eZH2 associated with malignant behavior in pancreatic IPMN via p27Kip1 downregulation?"
            ]
        },
        {
            "id": "task847-3a1e35d19cf74cf2b36c64d72dfee98d",
            "input": "To determine interrelationships between the expression of long intergenic (noncoding) RNA-p21 (lincRNA-p21), NF-\u03baB activity, and responses to methotrexate (MTX) in rheumatoid arthritis (RA) by analyzing patient blood samples and cell culture models.', 'Expression levels of long noncoding RNA and messenger RNA (mRNA) were determined by quantitative reverse transcription-polymerase chain reaction. Western blotting and flow cytometry were used to quantify levels of intracellular proteins. Intracellular NF-\u03baB activity was determined using an NF-\u03baB luciferase reporter plasmid.', 'Patients with RA expressed reduced basal levels of lincRNA-p21 and increased basal levels of phosphorylated p65 (RelA), a marker of NF-\u03baB activation. Patients with RA who were not treated with MTX expressed lower levels of lincRNA-p21 and higher levels of phosphorylated p65 compared with RA patients treated with low-dose MTX. In cell culture using primary cells and transformed cell lines, MTX induced lincRNA-p21 through a DNA-dependent protein kinase catalytic subunit (DNA PKcs)-dependent mechanism. Deficiencies in the levels of PRKDC mRNA in patients with RA were also corrected by MTX in vivo. Furthermore, MTX reduced NF-\u03baB activity in tumor necrosis factor \u03b1-treated cells through a DNA PKcs-dependent mechanism via induction of lincRNA-p21. Finally, we observed that depressed levels of TP53 and lincRNA-p21 increased NF-\u03baB activity in cell lines. Decreased levels of lincRNA-p21 did not alter NFKB1 or RELA transcripts; rather, lincRNA-p21 physically bound to RELA mRNA.",
            "output": [
                "Does methotrexate inhibit NF-\u03baB activity via long intergenic ( noncoding ) RNA-p21 induction?"
            ]
        },
        {
            "id": "task847-3c3c5b1673494ad0a01aa81b1d14767c",
            "input": "Infarct heterogeneity has been shown to be independently associated with adverse outcomes in previous smaller studies. However, it is unknown whether infarct characterization is an independent predictor of all-cause mortality in patients with advanced ischemic cardiomyopathy, after adjusting for clinical risk factors, severity of ischemic mitral regurgitation, incomplete revascularization, and device therapy.', 'A total of 362 patients with ischemic cardiomyopathy (left ventricular dysfunction with >70% stenosis in \u22651 epicardial coronary artery) underwent delayed hyperenhancement-magnetic resonance imaging and coronary angiography between 2002 and 2006. Total myocardial scar and peri-infarct (PI) area were measured using various threshold techniques. Multivariate survival analysis (primary end point of all-cause mortality) was conducted. One hundred fifty-seven deaths occurred during a mean 5.4-year follow-up (mean left ventricular ejection fraction, 23\u00b19%; mean end-systolic volume index, 113\u00b148 mL; mean total myocardial scar %, 25.5\u00b116.0%; mean PI%, 5.7\u00b12.9%). PI% (\u03b2=2.07; P<0.001) was an independent predictor of survival, independent of age, end-systolic volume, sex, mitral regurgitation, diabetes mellitus, dyslipidemia, coronary artery disease severity, implantable cardioverter defibrillator, and incomplete revascularization. PI% using 2 to 3 SD technique yielded the highest incremental prognostic power (\u03c7(2) score 149).",
            "output": [
                "Is infarct characterization and quantification by delayed enhancement cardiac magnetic resonance imaging a powerful independent and incremental predictor of mortality in patients with advanced ischemic cardiomyopathy?"
            ]
        },
        {
            "id": "task847-6fb2576c1f6f433c94d5e1189322c2ba",
            "input": "To compare turnover times for a series of elective cases with surgeons following themselves with turnover times for a series of previously scheduled elective procedures for which the succeeding surgeon differed from the preceding surgeon.', 'Retrospective cohort study.', 'University-affiliated teaching hospital.', 'The operating room (OR) statistical database was accessed to gather 32 months of turnover data from a large academic institution. Turnover time data for the same-surgeon and surgeon-swap groups were batched by month to minimize autocorrelation and achieve data normalization. Two-way analysis of variance (ANOVA) using the monthly batched data was performed with surgeon swapping and changes in procedure category as variables of turnover time. Similar analyses were performed using individual surgical services, hourly time intervals during the surgical day, and turnover frequency per OR as additional covariates to surgeon swapping.', 'The mean (95% confidence interval [CI]) same-surgeon turnover time was 43.6 (43.2 - 44.0) minutes versus 51.0 (50.5 - 51.6) minutes for a planned surgeon swap (P < 0.0001). This resulted in a difference (95% CI) of 7.4 (6.8 - 8.1) minutes. The exact increase in turnover time was dependent on surgical service, change in subsequent procedure type, time of day when the turnover occurred, and turnover frequency.",
            "output": [
                "Does elective change of surgeon during the OR day have an operationally negligible impact on turnover time?"
            ]
        },
        {
            "id": "task847-d08b921bf65b4c4499a13eeba95cb55e",
            "input": "It has previously been shown that gefitinib-treated patients with epidermal growth factor receptor (EGFR) gene amplification or high polysomy had a statistically significant improvement in response, time to progression, and survival in non-small cell lung cancer (NSCLC). Only few studies utilizing anti-EGFR treatment in advanced esophageal adenocarcinomas have been performed and the results have been heterogeneous. The aim of this study was to evaluate EGFR-targeted therapy with gefitinib in esophageal adenocarcinoma with a high EGFR polysomy.', 'Novel esophageal cell lines PT6216 and LN6216c were established from primary tumor and lymph node metastasis of a patient with highly aggressive and metastatic adenocarcinoma. Pathological examination including tumor differentiation and prognostic marker analysis, immunohistochemical EGFR expression analysis, EGFR fluorescence in situ hybridization, and mutation analysis were performed. Response of novel cell lines to gefitinib treatment was evaluated by cell proliferation and vitality assays. Fifty-four esophageal adenocarcinoma specimens were evaluated for EGFR gene copy gain.', 'The primary tumor cell line PT6216 and the lymph node cell line LN6216c show a homogenously high polysomy for EGFR determined by FISH analysis. Cell proliferation and vitality are highly sensitive to the tyrosine kinase inhibitor gefitinib compared to esophageal control cells without a high polysomy for EGFR. High polysomy for EGFR was found in 35 % of patients.",
            "output": [
                "Is esophageal carcinoma cell line with high EGFR polysomy responsive to gefitinib?"
            ]
        },
        {
            "id": "task847-ba0e37839ecc451e80a252d935300484",
            "input": "Colorectal cancer (CRC) screening is effective but underutilized. Although physician recommendation is an important predictor of screening, considerable variation in CRC screening completion remains.', 'To characterize the influence of patient trust in care providers on CRC screening behavior.', 'Data were collected as part of a cluster-randomized CRC screening intervention trial performed in the San Francisco Community Health Network from March 2007 to January 2012 (analysis, Spring 2012). All study participants received a recommendation to complete CRC screening from their primary care provider (PCP). Included participants were aged 50-79 years, not current with screening, and completed the Wake Forest Trust Scale (WFTS) measuring trust in PCPs and doctors in general. Primary outcome was CRC screening completion (colonoscopy or fecal occult blood testing) within 12 months following enrollment. Multivariable association adjusted for race/ethnicity, language, and other sociodemographics was estimated using generalized estimating equations with logit link and binomial distribution.', 'WFTS response was 70.3% (701). Most participants (83%) were Latino, Asian, or black. Most had income <$30,000 (96%) and public health insurance (86%). Higher trust in PCP was associated with screening completion (OR=1.11, 95% CI=1.03, 1.17), but trust in doctors was not (OR=1.02, 95% CI=0.82, 1.28). Race, language, and other sociodemographic factors were not significant in multivariable analysis.",
            "output": [
                "Does patient trust in physician influence colorectal cancer screening in low-income patients?"
            ]
        },
        {
            "id": "task847-9d076c2f6d9f417ea8807ecff7b16624",
            "input": "The aims of this study were to determine hyperoxia effects on S-nitrosothiol (SNO) accumulation and L-type amino acid transporter 1 (LAT1) expression/function in alveolar epithelium and to determine whether hyperoxia impairs exogenous nitric oxide (NO) treatment effects in alveolar epithelium through effects on LAT1 expression and/or function.', 'SNO accumulation in vitro and in vivo after NO treatment was dependent on the LAT1 system transport. Hyperoxia (60% or 90%) impaired NO effects on SNO accumulation and soluble guanylyl cyclase activation in proportion to the magnitude of hyperoxia and the duration of exposure, up to 12\\u2009h, in type I-like (R3/1) and type II-like (L2) rat and human (A549) alveolar epithelial cells. LAT function, determined by sodium-independent (3)H-leucine uptake, was impaired in a parallel manner. Hyperoxia impaired LAT1 expression in alveolar epithelial cells, determined by immunoblots and immunofluorescence, and in newborn rats exposed to 60% O2 for 4 days, determined by immunohistochemistry.', 'Despite significant preclinical evidence, inhaled NO has shown disappointing limitations in clinical applications. Our studies suggest an important explanation: oxidative stress, a common feature of diseases in which therapeutic NO would be considered, impairs LAT1 expression and function, blocking a major route for inhaled NO (iNO) action, that is, the uptake of S-nitrosocysteine via LAT1.",
            "output": [
                "Does hyperoxia inhibit nitric oxide treatment effects in alveolar epithelial cells via effects on L-type amino acid transporter-1?"
            ]
        },
        {
            "id": "task847-d0e3e0967f694656815f5828dd353fdb",
            "input": "SIRT2 belongs to a highly conserved family of NAD+-dependent deacylases, consisting of seven members (SIRT1-SIRT7), which vary in subcellular localizations and have substrates ranging from histones to transcription factors and enzymes. Recently SIRT2 was revealed to play an important role in inflammation, directly binding, deacetylating, and inhibiting the p65 subunit of NF-\u03baB.', 'A Sirt2 deficient mouse line (Sirt2-/-) was generated by deleting exons 5-7, encoding part of the SIRT2 deacetylase domain, by homologous recombination. Age- and sex-matched Sirt2-/- and Sirt2+/+ littermate mice were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility.', 'Sirt2-/- mice displayed more severe clinical and histological manifestations after DSS colitis compared to wild type littermates. Notably, under basal condition, Sirt2 deficiency does not affect the basal phenotype and intestinal morphology Sirt2 deficiency, however, affects macrophage polarization, creating a pro-inflammatory milieu in the immune cells compartment.",
            "output": [
                "Does sIRT2 deficiency modulate macrophage polarization and susceptibility to experimental colitis?"
            ]
        },
        {
            "id": "task847-5918a361557a497e81077d108ecc5064",
            "input": "There is controversy regarding the role of yttrium-90 (90Y) radioembolization in the management of advanced, unresectable hepatocellular carcinoma (HCC).', 'Forty-five consecutive patients underwent resin-based 90Y radioembolization for unresectable, HCC between 2006 and 2013 in Sydney, Australia. All patients were followed up with imaging studies at regular intervals until death. Radiologic response was evaluated with the Response Criteria in Solid Tumors (RECIST) criteria. Clinical toxicities were prospectively recorded. Survival was calculated by the Kaplan-Meier method and potential prognostic variables were identified on univariate and multivariate analysis.', 'Follow-up in the complete cohort was 7.8 (range, 0.1-41.8) months. The median survival after 90Y radioembolization was 27.7 months with a 36-month survival of 26%. By RECIST criteria of the 40 patients followed-up beyond 2 months, a complete response (CR) to treatment was observed in 1 patients (3%), partial response (PR) in 18 (45%), stable disease (SD) in 11 (22%) and progressive disease (PD) in 10 (25%). On multivariate analysis only radiological response to treatment was independently associated with improved survival: CR/PR to treatment vs. SD vs. PD; p\\xa0<\\xa00.001. Thirteen patients (29%) developed clinical toxicity after treatment; all complications were minor (grade I/II) and resolved without active intervention.",
            "output": [
                "Is yttrium-90 radioembolization a safe and effective treatment for unresectable hepatocellular carcinoma : a single centre experience of 45 consecutive patients?"
            ]
        },
        {
            "id": "task847-50367409d8d84779bb6432b1a62e58a7",
            "input": "Death from infection is a highly heritable trait, yet there are few genetic variants with known mechanism influencing survival during septic shock.', 'We hypothesized that a synonymous coding variant in the IL-1 receptor antagonist gene (IL1RN), rs315952, previously associated with reduced risk for acute respiratory distress syndrome, would be functional and associate with improved survival in septic shock.', 'We used a human endotoxin (LPS) model of evoked inflammatory stress to measure plasma IL-1 receptor antagonist (IL1RA) following low-dose Food and Drug Administration-grade LPS injection (1 ng/kg) in 294 human volunteers. RNA sequencing of adipose tissue pre- and post-LPS was used to test for allelic imbalance at rs315952. In the Vasopressin and Septic Shock Trial cohort, we performed a genetic association study for survival, mortality, and organ failure-free days.', 'Adipose tissue displayed significant allelic imbalance favoring the rs315952C allele in subjects of European ancestry. Consistent with this, carriers of rs315952C had slightly higher plasma IL1RA at baseline (0.039) and higher evoked IL1RA post-LPS (0.011). In the Vasopressin and Septic Shock Trial cohort, rs315952C associated with improved survival (P = 0.028), decreased adjusted 90-day mortality (P = 0.044), and faster resolution of shock (P = 0.029).",
            "output": [
                "Is a functional synonymous coding variant in the IL1RN gene associated with survival in septic shock?"
            ]
        },
        {
            "id": "task847-0d0f223b8a7e437fa8a00096b5946ac5",
            "input": "To assess plantarflexion moment and hip joint moment after-effects following walking on a split-belt treadmill in healthy individuals and individuals post-stroke.', 'Cross-sectional study.', 'Ten healthy individuals (mean age 57.6 years (standard deviation; SD 17.2)) and twenty individuals post-stroke (mean age 49.3 years (SD 13.2)).', 'Participants walked on an instrumented split-belt treadmill under 3 gait periods: i) baseline (tied-belt); ii) adaptation (split-belt); and iii) post-adaptation (tied-belt). Participants post-stroke performed the protocol with the paretic and nonparetic leg on the faster belt when belts were split. Kinematic data were recorded with the Optotrak system and ground reaction forces were collected via the instrumented split-belt treadmill.', 'In both groups, the fast plantarflexion moment was reduced and the slow plantarflexion moment was increased from mid-stance to toe-off in the post-adaptation period. Significant relationships were found between the plantarflexion moment and contralateral step length.",
            "output": [
                "Is plantarflexion moment a contributor to step length after-effect following walking on a split-belt treadmill in individuals with stroke and healthy individuals?"
            ]
        },
        {
            "id": "task847-31895a44946146f1a2a27b0c8418ecd9",
            "input": "Activation of extracellular signal-regulated kinase1/2 (ERK1/2) in dorsal horn of the spinal cord by peripheral inflammation is contributed to inflammatory pain hypersensitivity. Although electroacupuncture (EA) has been widely used to alleviate various kinds of pain, the underlying mechanism of EA analgesia requires further investigation. This study investigated the relationship between EA-induced analgesia and ERK signaling involved in pain hypersensitivity.', \"The rats were randomly divided into control, model, EA and sham EA groups. Inflammatory pain model was induced by injecting of 100 \u03bcl Complete Freund's adjuvant (CFA) into the plantar surface of a hind paw. Rats in the EA group were treatment with EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1-2 mA) at 5.5 h, 24.5 h and 48.5 h. Paw withdrawal thresholds (PWTs) were measured before modeling and at 5 h, 6 h, 25 h and 49 h after CFA injection. Rats were killed and ipsilateral side of the lumbar spinal cords were harvested for detecting the expressions of p-ERK1/2, Elk1, COX-2, NK-1 and CREB by immunohistochemistry, real-time PCR, western blot analysis and EMSA. Finally, the analgesic effect of EA plus U0126, a MEK (ERK kinase) inhibitor, on CFA rats was examined.\", 'Inflammatory pain was induced in rats by hindpaw injection of CFA and significantly increased phospho-ERK1/2 positive cells and protein levels of p-ERK1/2 in the ipsilateral spinal cord dorsal horn (SCDH). CFA up-regulated of cyclooxygenase-2 (COX-2) mRNA and protein expression at 6 h after injection and neurokinin-1 receptor (NK-1) expression at 49 h post-injection, in the SCDH. EA, applied to Zusanli (ST36) and Kunlun (BL60), remarkably increased the pain thresholds of CFA injected rats, significantly suppressed ERK1/2 activation and COX-2 protein expression after a single treatment, and decreased NK-1 mRNA and protein expression at 49 h. EA decreased the DNA binding activity of cAMP response element binding protein (CREB), a downstream transcription factor of ERK1/2, at 49 h after CFA injection. Moreover, EA and U0126 synergistically inhibited CFA-induced allodynia.",
            "output": [
                "Does electroacupuncture mediate extracellular signal-regulated kinase 1/2 pathways in the spinal cord of rats with inflammatory pain?"
            ]
        },
        {
            "id": "task847-12299c17d7444410852ab473cefd2ed6",
            "input": "Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. We hypothesised that changes in mitochondrial metabolic intermediates would predict improvements in clinical risk factors, thereby offering novel insights into potential mechanisms.', 'Subjects at risk of metabolic disease were randomised to 6\\xa0months of inactivity or one of five aerobic and/or resistance training programmes (n\\u2009=\\u2009112). Pre/post-intervention assessments included cardiorespiratory fitness ([Formula: see text]), serum triacylglycerols (TGs) and insulin sensitivity (SI). In this secondary analysis, muscle biopsy specimens were used for targeted mass spectrometry-based analysis of metabolic intermediates and measurement of mRNA expression of genes involved in metabolism.', 'Exercise regimens with the largest energy expenditure produced robust increases in muscle concentrations of even-chain acylcarnitines (median 37-488%), which correlated positively with increased expression of genes involved in muscle uptake and oxidation of fatty acids. Along with free carnitine, the aforementioned acylcarnitine metabolites were related to improvements in [Formula: see text], TGs and SI (R\\u2009=\\u20090.20-0.31, p\\u2009<\\u20090.05). Muscle concentrations of the tricarboxylic acid cycle intermediates succinate and succinylcarnitine (R\\u2009=\\u20090.39 and 0.24, p\\u2009<\\u20090.05) emerged as the strongest correlates of SI.",
            "output": [
                "Do metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness?"
            ]
        },
        {
            "id": "task847-b3791896198840ada61341e63952df25",
            "input": "Rectal cancer has a higher risk of developing lung metastasis compared with colon cancer. It is unclear whether the prognosis after pulmonary metastasectomy for these distinct tumors is different.', 'Patients who underwent pulmonary metastasectomy for colorectal carcinoma were analyzed for survival and patterns of recurrence depending on the location of the primary colorectal cancer. Multivariate regression analysis was performed to identify clinical variables predictive of survival after pulmonary metastasectomy.', 'Between 1985 and 2012, 698 patients underwent pulmonary metastasectomy for metastatic colorectal cancer. Complete information was available in 626 patients. These patients were divided into groups based on whether the primary tumor was colon or rectal in origin. Median follow-up was 45.5 months (range, 23 to 287 months). There were no statistical differences between the two groups in terms of number of lung metastases, tumor size, or lymph node involvement. There was no difference in overall survival (p\\xa0= 0.545). Five-year disease-free survival for colon cancer patients was 67.2% compared with 60.1% for rectal cancer (p\\xa0= 0.004). The most common sites of recurrence after pulmonary metastasectomy were liver in colon cancer and lung in rectal cancer. Multivariate Cox proportional hazards analysis indicated that rectal cancer (hazard ratio, 1.39; 95% confidence interval, 1.07 to 1.83; p\\xa0= 0.015) and multiple metastases (>3; hazard ratio, 1.41; 95% confidence interval, 1.04 to 1.89; p\\xa0= 0.027) were independent adverse risk factors affecting disease-free survival after pulmonary metastasectomy.",
            "output": [
                "Does the prognosis of pulmonary metastasectomy depend on the location of the primary colorectal cancer?"
            ]
        },
        {
            "id": "task847-893608d8c68b43219183cf11a4e62968",
            "input": "Bariatric surgery not only elicits weight loss but also rapidly resolves diabetes. However, the mechanisms remain unclear. The present study investigates how diabetes and liver steatosis are improved after duodenal-jejunal bypass (DJB) compared with a glucagon-like peptide-1 (GLP-1) analog and correlations between bile acids and GLP-1 secretion.', 'We initially determined the effects of bile acids on GLP-1 in vitro and then assigned 12 male 16-week-old Otsuka Long-Evans Tokushima Fatty rats to groups that underwent DJB, a sham operation, or were treated with the GLP-1 receptor agonist, liraglutide (n\\u2009=\\u20094 each). Blood glucose, insulin, GLP-1, serum bile acids, liver steatosis, and the number of GLP-1 positive cells (L cells) in the small intestine and colon were investigated in the three groups at eight weeks postoperatively.', 'Levels of GLP-1mRNA were upregulated and GLP-1 secretion increased in cells incubated with bile acids in vitro. Weight gain was suppressed more in the DJB than in the sham group in vivo. Diabetes was more improved and GLP-1 levels were significantly higher in the DJB than in the sham group. Serum bile acids were significantly increased, the number of L cells in the ileum was upregulated compared with the sham group, and liver steatosis was significantly improved in the DJB compared with the other two groups.",
            "output": [
                "Does duodenal-jejunal bypass improve diabetes and liver steatosis via enhanced glucagon-like peptide-1 elicited by bile acids?"
            ]
        },
        {
            "id": "task847-98cc4a2d6b3b49b49635e3e2566f56c4",
            "input": "Traumatic intestinal injuries are less common with blunt compared to penetrating mechanisms of trauma and blunt injuries are often associated with diagnostic delays. The purpose of this study is to evaluate differences in the characteristics and outcomes between blunt and penetrating intestinal injuries to facilitate insight into optimal recognition and management.', 'A retrospective analysis of trauma admissions from January 2009 to June 2011 was performed. Patient demographics, ISS, early shock, injury type, timing to OR, blood loss and transfusions, surgical management, infections, EC fistulas, enteric leaks, LOS and mortality were compared.', 'Demographics - There was 3866 blunt admissions and 966 penetrating admissions to our level II trauma centre (Total n=4832) during this interval. The final study group comprised n=131 patients treated for intestinal injuries. Blunt n=54 (BI) vs. penetrating (PI) n=77. Age was similar between the groups: (BI 34 SD 12 vs. PI 30 SD 12). Comorbid conditions were similar as were ED hypotension and blood transfusions. Blunt mechanisms had higher ISS; BI (20 SD 14) vs. PI (16 SD 12), p=0.08 and organ specific injury scales were higher in blunt injuries. Operative Management - Time to operation was higher in BI: (500 SD 676min vs. PI 110 SD 153min, p=0.01). The use of an open abdomen technique was higher for BI: n=19 (35%) vs. PI: n=5 (6%), p=<0.001, as well as delayed intestinal repair in damage control cases. Outcomes - Anastomotic leaks were more prevalent in BI: n=4 (7%) vs. PI: n=2 (3%), p=0.38. Enteric fistulas were: (BI n=8 (15%), vs. PI n=2 (3%), p=0.02). Surgical site infections and other nosocomial infections were: (BI n=11 (20%) vs. PI n=4 (5%), p=0.02), (BI n=11 (20%) vs. PI n=2 (3%), p=0.002), respectively. Hospital and ICU LOS was: (BI=20 SD 14 vs. PI=11 SD 11, p=0.001), (BI=10 SD 10 vs. PI=5 SD 5, p=0.01) respectively. These differences were reflected in higher hospital charges in BI.",
            "output": [
                "Are not all intestinal traumatic injuries the same : a comparison of surgically treated blunt vs. penetrating injuries?"
            ]
        },
        {
            "id": "task847-b8c1020dbba5442a8b8bd55dc1a96e86",
            "input": "We have previously reported the crucial roles of oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) in inhibiting apoptosis and disrupting cell polarity via the regulation of phosphodiesterase 4 (PDE4) expression in human colorectal cancer HCT116 cells in three-dimensional cultures (3DC). Herein we evaluated the effects of resveratrol, a PDE4 inhibitor, on the luminal cavity formation and the induction of apoptosis in HCT116 cells.', 'Apoptosis was detected by immunofluorescence using confocal laser scanning microscopy with an antibody against cleaved caspase-3 in HCT116 cells treated with or without resveratrol in a two-dimensional culture (2DC) or 3DC.', 'Resveratrol did not induce apoptosis of HCT116 cells in 2DC, whereas the number of apoptotic HCT116 cells increased after resveratrol treatment in 3DC, leading to formation of a luminal cavity.",
            "output": [
                "Does resveratrol induce luminal apoptosis of human colorectal cancer HCT116 cells in three-dimensional culture?"
            ]
        },
        {
            "id": "task847-f0c314da85b04428af3777169162746e",
            "input": "Fenestrated endovascular aortic aneurysm repair (FEVAR) is an alternative to open repair in patients with complex abdominal aortic aneurysms who are neither fit nor suitable for standard open or endovascular repair. Chimney and snorkel grafts are other endovascular alternatives but frequently require bilateral upper extremity access that has been associated with a 3% to 10% risk of stroke. However, upper extremity access is also frequently required for FEVAR because of the caudal orientation of the visceral vessels. The purpose of this study was to assess the use of upper extremity access for FEVAR and the associated morbidity.', 'During a 5-year period, 148 patients underwent FEVAR, and upper extremity access for FEVAR was used in 98 (66%). Outcomes were compared between those who underwent upper extremity access and those who underwent femoral access alone. The primary end point was a cerebrovascular accident or transient ischemic attack, and the secondary end point was local access site complications. The mean number of fenestrated vessels was 3.07 \u00b1 0.81 (median, 3) for a total of 457 vessels stented. Percutaneous upper extremity access was used in 12 patients (12%) and open access in 86 (88%). All patients who required a sheath size >7F underwent high brachial open access, with the exception of one patient who underwent percutaneous axillary access with a 12F sheath. The mean sheath size was 10.59F \u00b1 2.51F (median, 12F), which was advanced into the descending thoracic aorta, allowing multiple wire and catheter exchanges.', 'One hemorrhagic stroke (one of 98 [1%]) occurred in the upper extremity access group, and one ischemic stroke (one of 54 [2%]) occurred in the femoral-only access group (P = .67). The stroke in the upper extremity access group occurred 5 days after FEVAR and was related to uncontrolled hypertension, whereas the stroke in the femoral group occurred on postoperative day 3. Neither patient had signs or symptoms of a stroke immediately after FEVAR. The right upper extremity was accessed six times without a stroke (0%) compared with the left being accessed 92 times with one stroke (1%; P = .8). Four patients (4%) had local complications related to upper extremity access. One (1%) required exploration for an expanding hematoma after manual compression for a 7F sheath, one (1%) required exploration for hematoma and neurologic symptoms after open access for a 12F sheath, and two patients (2%) with small hematomas did not require intervention. Two (two of 12 [17%]) of these complications were in the percutaneous access group, which were significantly more frequent than in the open group (two of 86 [2%]; P = .02).",
            "output": [
                "Is upper extremity access for fenestrated endovascular aortic aneurysm repair associated with increased morbidity?"
            ]
        },
        {
            "id": "task847-a48f34504c074c7ea7154a6f2386bf19",
            "input": "S-adenosyl-l-homocysteine hydrolase (SAHH) is the only eukaryotic enzyme capable of S-adenosyl-l-homocysteine (SAH) catabolism for the maintenance of cellular transmethylation potential. Recently, biochemical and genetic studies in herbaceous species have obtained important discoveries in the function of SAHH, and an extensive characterization of SAHH family in even one tree species is essential, but currently lacking.', 'Here, we first identified the SAHH family from Populus tomentosa using molecular cloning method. Phylogenetic analyses of 28 SAHH proteins from dicotyledons, monocotyledons, and lower plants revealed that the sequences formed two monophyletic groups: the PtrSAHHA with PtoSAHHA and PtrSAHHB with PtoSAHHB. Examination of tissue-specific expression profiles of the PtoSAHH family revealed similar expression patterns; high levels of expression in xylem were found. Nucleotide diversity and linkage disequilibrium (LD) in the PtoSAHH family, sampled from P. tomentosa natural distribution, revealed that PtoSAHH harbors high single-nucleotide polymorphism (SNP) diversity (\u03c0 = 0.01059 \u00b1 0.00122 and 0.00930 \u00b1 0.00079,respectively) and low LD (r2 > 0.1, within 800 bp and 2,200 bp, respectively). Using an LD-linkage analysis approach, two noncoding SNPs (PtoSAHHB_1065 and PtoSAHHA_2203) and the corresponding haplotypes were found to significantly associate with \u03b1-cellulose content, and a nonsynonymous SNP (PtoSAHHB_410) within the SAHH signature motifs showed significant association with fiber length, with an average of 3.14% of the phenotypic variance explained.",
            "output": [
                "Is allelic variation within the S-adenosyl-L-homocysteine hydrolase gene family associated with wood properties in Chinese white poplar ( Populus tomentosa )?"
            ]
        },
        {
            "id": "task847-7135c904edb54423b29c648d2e467a2b",
            "input": "Maternal overnutrition during pregnancy is associated with an increased risk of obesity and cardiometabolic disease in the offspring; a phenomenon attributed to 'developmental programming'. The post-weaning development of obesity may associate with exacerbation of the programmed metabolic phenotype. In mice, we have previously shown that exposure to maternal overnutrition causes increased weight gain in offspring before weaning, but exerts no persistent effects on weight or glucose tolerance in adulthood. In order to determine whether post-weaning exposure to a cafeteria diet might lead to an exacerbation of programmed effects, offspring born and raised by mothers on control (CON) or cafeteria (DIO) diets were transferred onto either CON or DIO diets at weaning.\", 'Post-weaning DIO caused the development of obesity, with hyperglycaemia and hyperinsulinaemia in males; and obesity with hyperinsulinaemia in females and with increased cholesterol levels in both sexes. Exposure to maternal overnutrition during pregnancy and lactation caused only subtle additional effects on offspring phenotype.",
            "output": [
                "Does post-weaning diet determine metabolic risk in mice exposed to overnutrition in early life?"
            ]
        },
        {
            "id": "task847-bac046cb57cb456d8d525d24f0534778",
            "input": "This study used dopamine D2 receptor (D2R) knockout (KO) mice to investigate the role of D2R activity in the development of form-deprivation myopia (FDM). Sulpiride, a D2R antagonist, was administered systemically into wild-type (WT) mice to validate the involvement of D2R in FDM development.', 'The D2R KO and WT C57BL/6 mice were subjected to FDM. Wild-type mice received daily intraperitoneal injections of sulpiride, 8 \u03bcg/g body weight, for a period of 4 weeks. The body weight, refraction, corneal radius of curvature, and ocular axial components were measured at week 4 of the experiment. Differences in all ocular parameters between the experimental and control groups were compared statistically.', 'Form-deprivation myopia in D2R KO mice (FD-KO) was significantly reduced compared with their WT littermates (interocular difference, -2.12 \u00b1 0.91 diopter [D] in FD-KO versus -5.35 \u00b1 0.83 D in FD-WT, P = 0.014), with a smaller vitreous chamber depth (0.008 \u00b1 0.006 vs. 0.026 \u00b1 0.006 mm, P = 0.044) and axial length (-0.001 \u00b1 0.007 vs. 0.027 \u00b1 0.008 mm, P = 0.007). Furthermore, FDM was attenuated in animals treated with sulpiride (-2.01 \u00b1 0.31 D in FD-sulpiride versus -4.06 \u00b1 0.30 D in FD-DMSO, P < 0.001) compared with those treated with vehicle, with a retardation in growth of vitreous chamber depth (-0.001 \u00b1 0.006 vs. 0.022 \u00b1 0.004 mm, P = 0.003) and axial length (-0.004 \u00b1 0.007 vs. 0.027 \u00b1 0.005 mm, P = 0.001).",
            "output": [
                "Is activation of dopamine D2 receptor critical for the development of form-deprivation myopia in the C57BL/6 mouse?"
            ]
        },
        {
            "id": "task847-f9e61e7a6c694a7b89679199c1515263",
            "input": "Retinal ischemia/reperfusion (IR) is common in eye disorders. Pattern-recognition receptors (PRRs) are reported to initiate sterile inflammatory response. The role of PRRs in retinal IR injury is currently unknown. Thus, we investigated the expression and function of membrane and cytoplasmic PRRs during retinal IR.', 'Retinal IR was induced in adult Brown Norway rats by clipping the retinal vessels for 30 minutes. RNA and proteins were extracted during the course of reperfusion, and the expression levels of the following proteins were determined: Toll-like receptor 2 (TLR2), TLR4, myeloid differentiation factor 88 (MyD88), TNF receptor-associated factor 6 (TRAF6), nuclear factor-\u03baB (NF-\u03baB), nucleotide-binding oligomerization domain-like receptor with pyrin domain protein 1 (NLRP1), NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, IL-1\u03b2, and IL-18. TLR4 expression in the retina was studied using immunohistochemistry. In addition, a TLR4 inhibitor was injected into the vitreous body as a therapeutic agent. After the treatment of TLR4 inhibitors, the levels of the above factors were evaluated, the apoptosis of cells in the retina, expression of cleaved-caspase-3 (c-casp-3), death of retinal ganglion cells, and the retina electroretinography was assessed.', 'After releasing the artery clamp, the retinal vessels were reperfused in 5 minutes. During the reperfusion, TLR4, MyD88, TRAF6, NF-\u03baB, NLRP1, NLRP3, mature IL-1\u03b2, and IL-18 were upregulated, but not TLR2. In the IR model, TLR4 was highly expressed in ganglion cell and glia cell. Additionally, the inhibition of TLR4 significantly downregulated the activation of NLRP3, but not NLRP1, and the secretion of mature IL-1\u03b2 and IL-18 also were inhibited. Moreover, the TLR4 inhibitor partially attenuated the injury of the retina, including alleviated retina apoptosis, downregulated c-casp-3 expression, rescued retinal ganglion cells death, and restored retina function.",
            "output": [
                "Is retinal ischemia/reperfusion injury mediated by Toll-like receptor 4 activation of NLRP3 inflammasomes?"
            ]
        },
        {
            "id": "task847-9821c5b8cb0a484b9264a65f38adb26d",
            "input": "We investigated suspected food intolerances in patients with irritable bowel syndrome (IBS) using confocal laser endomicroscopy (CLE) for real-time visualization of structural/functional changes in the intestinal mucosa after food challenge. Patients with functional changes after food challenge (CLE+) were placed on personalized exclusion diets and followed up for long-term symptom relief.', \"Thirty-six IBS patients with suspected food intolerance and 10 patients with Barrett's esophagus (controls) without IBS symptoms were examined by CLE at University Hospital Schleswig-Holstein (Kiel, Germany). Diluted food antigens were administered directly to the duodenal mucosa through the working channel of the endoscope. Epithelial breaks, intervillous spaces, and the number of intraepithelial lymphocytes (IEL) were measured before and after the food challenge. CLE+ patients were placed on exclusion diets, given symptom score questionnaires, and followed up for 1 year; controls resumed their previous diet.\", 'CLE showed a real-time response to food antigens in 22 of 36 patients; no responses were observed in 14 of 36 patients (CLE-) or any of the controls. Baseline IELs were significantly higher in CLE+ than CLE- subjects (P\\xa0= .004); numbers increased significantly after food challenge (P\\xa0= .0008). Within 5 minutes of exposure of CLE+ patients to food antigens, IELs increased, epithelial leaks/gaps formed, and intervillous spaces widened. Epithelial leaks and intervillous spaces also increased significantly in CLE+ vs baseline (both P < .001). The concordance of IELs measured by CLE and conventional histology was 70.6%; they did not correlate (P\\xa0= .89; r(2)\\xa0= 0.027). Symptom scores improved more than 50% in CLE+ patients after a 4-week exclusion diet and increased to 74% at 12 months; symptoms continued in CLE- patients.",
            "output": [
                "Does confocal endomicroscopy show food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome?"
            ]
        },
        {
            "id": "task847-c2dd91b37cc84180bbbbe3dd4a292c3c",
            "input": "Serum cystatin C has been established as a predictor of cardiovascular events. The aim of this study was to evaluate the role of cystatin C in determining the presence and the severity of patients with coronary artery disease (CAD).', 'A total of 936 subjects without overt renal disease were included in this cross-sectional study. Among them were 714 patients with CAD and 222 without based on coronary angiography. Subjects were further divided into four groups according to cystatin C quartile. Serum cystatin C was measured using particle-enhanced immunoassay method. The study analyzed the relationship of cystatin C levels with the presence and severity of CAD, including the number of stenotic vessels involved and Gensini score.', 'Serum cystatin C levels were significantly higher in patients with CAD than those without (P<0.001), and significantly increased as the involvement of coronary vessels increased (P<0.001). The prevalence of CAD and its severity assessed by Gensini score were also significantly greater in the highest quartile of cystatin C (P<0.001). Moreover, cystatin C levels were independently correlated with the presence of CAD in a multivariate logistic regression model (P=0.023) and were positively correlated with Gensini score by linear regression analysis (standardized \u03b2=0.083, P=0.010).",
            "output": [
                "Are serum cystatin C levels associated with coronary artery disease and its severity?"
            ]
        },
        {
            "id": "task847-1196ed4706c64c47a1402a425e2cbea0",
            "input": "Autologous mesenchymal stem cells (MSCs) are an attractive concept in regenerative medicine, but their mechanism of action remains poorly defined. No immune response is reported after in vivo injection of allogeneic equine MSCs or embryo-derived stem cells (ESCs) into the equine tendon, which may be due to the cells' immune-privileged properties. This study further investigates these properties to determine their potential for clinical application in other tissues.\", 'Mitomycin C-treated MSCs, ESCs, or differentiated ESCs (dESCs) were cultured with allogeneic equine peripheral blood mononuclear cells (PBMCs), and their effect on PBMC proliferation, in the presence or absence of interferon-gamma (IFN-\u03b3) was determined. MSCs and super-antigen (sAg)-stimulated PBMCs were co-cultured directly or indirectly in transwells, and PBMC proliferation examined. Media from MSC culture were harvested and used for PBMC culture; subsequent PBMC proliferation and gene expression were evaluated and media assayed for IFN-\u03b3, tumor necrosis factor alpha (TNF-\u03b1), and interleukin (IL)-10 and IL-6 proteins with enzyme-linked immunosorbent assay (ELISA).', 'Co-culture of PBMCs with ESCs or dESCs did not affect baseline proliferation, whereas co-culture with MSCs significantly suppressed baseline proliferation. Stimulation of PBMC proliferation by using super-antigens (sAgs) was also suppressed by co-culture with MSCs. Inhibition was greatest with direct contact, but significant inhibition was produced in transwell culture and by using MSC-conditioned media, suggesting that soluble factors play a role in MSC-mediated immune suppression. The MSCs constitutively secrete IL-6, even in the absence of co-culture with PBMCs. MSC-conditioned media also brought about a change in the cytokine-expression profile of sAg-stimulated PBMCs, significantly reducing PBMC expression of IL-6, IFN-\u03b3, and TNF-\u03b1.",
            "output": [
                "Are equine mesenchymal stromal cells and embryo-derived stem cells immune privileged in vitro?"
            ]
        },
        {
            "id": "task847-aa34ddfbcc9244ab974178e5ed01e356",
            "input": "To investigate which single quantitative electro-encephalographic (QEEG) marker or which combination of markers correlates best with Alzheimer's disease (AD) severity as measured by the Mini-Mental State Examination (MMSE).\", 'We compared quantitative EEG markers for slowing (relative band powers), synchrony (coherence, canonical correlation, Granger causality) and complexity (auto-mutual information, Shannon/Tsallis entropy) in 118 AD patients from the multi-centric study PRODEM Austria. Signal spectra were determined using an indirect spectral estimator. Analyses were adjusted for age, sex, duration of dementia, and level of education.', 'For the whole group (39 possible, 79 probable AD cases) MMSE scores explained 33% of the variations in relative theta power during face encoding, and 31% of auto-mutual information in resting state with eyes closed. MMSE scores explained also 25% of the overall QEEG factor. This factor was thus subordinate to individual markers. In probable AD, QEEG coefficients of determination were always higher than in the whole group, where MMSE scores explained 51% of the variations in relative theta power.",
            "output": [
                "Do quantitative EEG markers relate to Alzheimer 's disease severity in the Prospective Dementia Registry Austria ( PRODEM )?"
            ]
        },
        {
            "id": "task847-311717ce447248938da9e7c6639e9a91",
            "input": "The study compared two channel-reduction approaches in order to investigate the effects of systematic motor imagery (MI) neurofeedback practice in an everyday environment using a very user-friendly EEG system consisting of individualized caps and highly portable hardware.', 'Sixteen BCI novices were trained over four consecutive days to imagine left and right hand movements while receiving feedback. The most informative bipolar channels for use on the subsequent days were identified on the first day for each individual based on a high-density online MI recording.', 'Online classification accuracy on the first day was 85.1% on average (range: 64.7-97.7%). Offline an individually-selected bipolar channel pair based on common spatial patterns significantly outperformed a pair informed by independent component analysis and a standard 10-20 pair. From day 2 to day 4 online MI accuracy increased significantly (day 2: 69.1%; day 4: 73.3%), which was mostly caused by a reduction in ipsilateral event-related desynchronization of sensorimotor rhythms.",
            "output": [
                "Does wireless EEG with individualized channel layout enable efficient motor imagery training?"
            ]
        },
        {
            "id": "task847-3c5c57e996614acc85ce8f3e2a3dac23",
            "input": "Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy associated with poor survival rates. Fast detection of PDAC appears to be the most relevant strategy to improve the long-term survival of patients.', 'Our objective was to identify new markers in peripheral blood that differentiates between PDAC patients and healthy controls.', 'Peripheral blood samples from PDAC patients (n\\xa0=\\xa018) and controls (n\\xa0=\\xa018) were analyzed by whole genome cDNA microarray hybridization. The most relevant genes were validated by quantitative real-time PCR (RT-qPCR) in the same set of samples. Finally, our gene prediction set was tested in a blinded set of new peripheral blood samples (n\\xa0=\\xa030).', 'Microarray studies identified 87 genes differentially expressed in peripheral blood samples from PDAC patients. Four of these genes were selected for analysis by RT-qPCR, which confirmed the previously observed changes. In our blinded validation study, the combination of CLEC4D and IRAK3 predicted the diagnosis of PDAC with 93\\xa0% accuracy, with a sensitivity of 86\\xa0% and specificity of 100\\xa0%.",
            "output": [
                "Does transcriptional profiling of peripheral blood in pancreatic adenocarcinoma patients identify diagnostic biomarkers?"
            ]
        },
        {
            "id": "task847-a99c1eaec8554e0e9930ee7a2d6f3bc7",
            "input": "The aim of the study was to determine whether medial meniscal substitution with a polyurethane scaffold (Actifit(\u00ae)) improves the outcome of medial meniscal-deficient varus knees undergoing open-wedge high tibial osteotomy.', 'Sixty patients with symptomatic varus knees those who underwent open-wedge high tibial osteotomies were prospectively studied. In 30 patients, the medial meniscus was left with a defect larger than 25 mm (Group M). An Actifit(\u00ae) device was implanted (Group A) in the remaining 30 patients. Patients were functionally evaluated with WOMET, IKDC and VAS. Patient satisfaction was graded from 0 (not satisfied) to 4 (very satisfied).', 'Both groups were comparable preoperatively. They had similar follow-up periods (31.2 months; range 24-47.5; n.s.). WOMET improved a mean of 53.4 \u00b1 8.4 and 42.4 \u00b1 17.2 points in Groups M and A, respectively (p = 0.002). IKDC improved a mean of 56.7 \u00b1 12 and 50.3 \u00b1 15.6 points in Groups M and A, respectively (n.s.). VAS dropped 5.9 \u00b1 2.1 and 4.7 \u00b1 2.8 points in Groups M and A, respectively (p = 0.006). Patient satisfaction averaged 3.3 \u00b1 0.8 and 3.3 \u00b1 1 in Groups M and A, respectively (n.s.).",
            "output": [
                "Does partial meniscus substitution with a polyurethane scaffold improve outcome after an open-wedge high tibial osteotomy?"
            ]
        },
        {
            "id": "task847-9ea3ee06102046af88cc5f360dc0953e",
            "input": "Epithelial-to-mesenchymal transition (EMT) is generally associated with increased tumor aggressiveness and poor prognosis. We evaluated EMT characteristics in intraductal papillary mucinous neoplasm (IPMN) tumor specimens and their potential role as biomarkers for malignancy, metastasis, and adverse patient outcomes.', 'IPMN surgical specimens were identified and reviewed by two gastrointestinal pathologists. Immunohistochemical analysis of E-cadherin, vimentin, and ZEB-1 was performed. Samples were linked to clinicopathologic and outcome data for these patients. Western blot test was used to evaluate ZEB-1 expression in IPMN samples; 846 human miRNAs were profiled, and EMT-related differentially expressed miRNAs were validated using quantitative real-time polymerase chain reaction.', 'Fifty-eight IPMN specimens and five normal pancreatic tissue samples were immunohistochemically stained and scored. E-cadherin expression was significantly lower in malignant versus low-grade IPMN (p < 0.05). Vimentin expression was increased in malignant IPMN tumor samples (p < 0.05). EMT was associated with increased lymph node metastasis and decreased survival of malignant IPMN patients (p < 0.05). ZEB-1, an imperative EMT regulator, was exclusively expressed by malignant IPMN tumors. miRNA hierarchical clustering demonstrated grouping of two main IPMN subgroups: low-grade IPMN versus high-grade IPMN and carcinoma. Twenty-four miRNAs were differentially expressed (14 up-regulated, 10 down-regulated). The EMT-regulatory miRNAs, miR-200c and miR-141, were down-regulated (twofold and 1.8-fold decrease, respectively) in malignant versus low-grade IPMN (p < 0.05).",
            "output": [
                "Is epithelial-to-mesenchymal transition ( EMT ) in intraductal papillary mucinous neoplasm ( IPMN ) associated with high tumor grade and adverse outcomes?"
            ]
        },
        {
            "id": "task847-d28131881d07433d872d5d3d475f0a16",
            "input": "Inflammation triggered by infection or injury is tightly controlled by glucocorticoid hormones which signal via a dedicated transcription factor, the Glucocorticoid Receptor (GR), to regulate hundreds of genes. However, the hierarchy of transcriptional responses to GR activation and the molecular basis of their oftentimes non-linear dynamics are not understood.', 'We investigated early glucocorticoid-driven transcriptional events in macrophages, a cell type highly responsive to both pro- and anti-inflammatory stimuli. Using whole transcriptome analyses in resting and acutely lipopolysaccharide (LPS)-stimulated macrophages, we show that early GR target genes form dense networks with the majority of control nodes represented by transcription factors. The expression dynamics of several glucocorticoid-responsive genes are consistent with feed forward loops (FFL) and coincide with rapid GR recruitment. Notably, GR binding sites in genes encoding members of the KLF transcription factor family colocalize with KLF binding sites. Moreover, our gene expression, transcription factor binding and computational data are consistent with the existence of the GR-KLF9-KLF2 incoherent FFL. Analysis of LPS-downregulated genes revealed striking enrichment in multimerized Zn-fingers- and KRAB domain-containing proteins known to bind nucleic acids and repress transcription by propagating heterochromatin. This raises an intriguing possibility that an increase in chromatin accessibility in inflammatory macrophages results from broad downregulation of negative chromatin remodelers.",
            "output": [
                "Does glucocorticoid receptor coordinate transcription factor-dominated regulatory network in macrophages?"
            ]
        },
        {
            "id": "task847-79dbfab9aa3c41cca367212a913f535f",
            "input": "Kr\u00fcpple-like factor 5 (KLF5) is a transcription factor that is highly expressed in the proliferative compartment of the intestinal crypt. There, it is thought to regulate epithelial turnover and homeostasis.', 'In this study, we sought to determine the role for Klf5 in the maintenance of cellular proliferation, cytodifferentiation, and morphology of the crypt-villus axis.', 'Tamoxifen-induced recombination directed by the epithelial-specific Villin promoter (in Villin-CreERT2 transgenic mice) was used to delete Klf5 (in Klf5 (loxP/loxP) mice) from the adult mouse intestine and analyzed by immunostaining and RT-qPCR. Control mice were tamoxifen-treated Klf5 (loxP/loxP) mice lacking Villin-CreERT2.', 'Three days after tamoxifen-induced recombination, the mitosis marker phospho-histone H3 was significantly reduced within the Klf5-mutant crypt epithelium, coincident with increased expression of the apoptosis marker cleaved-caspase 3 within the crypt where cell death rarely occurs normally. We also observed a reduction in Chromagranin A expressing enteroendocrine cells, though no significant change was seen in other secretory or absorptive cell types. To examine the long-term repercussions of Klf5 loss, we killed mice 5, 14, and 28 days post recombination and found reemerging expression of KLF5. Furthermore, we observed restoration of cellular proliferation, though not to levels seen wildtype intestinal crypts. Reduction of apoptosis to levels comparable to the wildtype intestinal crypt was also observed at later time points. Analysis of cell cycle machinery indicated no significant perturbation upon deletion of Klf5; however, a reduction of stem cell markers Ascl2, Lgr5, and Olfm4 was observed at all time points following Klf5 deletion.",
            "output": [
                "Is kr\u00fcpple-like factor 5 required for proper maintenance of adult intestinal crypt cellular proliferation?"
            ]
        },
        {
            "id": "task847-16a8a53b84394ac7812dc19aa342494a",
            "input": "Inactivating mutations in the Forkhead Box transcription factor F1 (FOXF1) gene locus are frequently found in patients with alveolar capillary dysplasia with misalignment of pulmonary veins, a lethal congenital disorder, which is characterized by severe abnormalities in the respiratory, cardiovascular, and gastrointestinal systems. In mice, haploinsufficiency of the Foxf1 gene causes alveolar capillary dysplasia and developmental defects in lung, intestinal, and gall bladder morphogenesis.', 'Although FOXF1 is expressed in multiple mesenchyme-derived cell types, cellular origins and molecular mechanisms of developmental abnormalities in FOXF1-deficient mice and patients with alveolar capillary dysplasia with misalignment of pulmonary veins remain uncharacterized because of lack of mouse models with cell-restricted inactivation of the Foxf1 gene. In the present study, the role of FOXF1 in endothelial cells was examined using a conditional knockout approach.', 'A novel mouse line harboring Foxf1-floxed alleles was generated by homologous recombination. Tie2-Cre and Pdgfb-CreER transgenes were used to delete Foxf1 from endothelial cells. FOXF1-deficient embryos exhibited embryonic lethality, growth retardation, polyhydramnios, cardiac ventricular hypoplasia, and vascular abnormalities in the lung, placenta, yolk sac, and retina. Deletion of FOXF1 from endothelial cells reduced endothelial proliferation, increased apoptosis, inhibited vascular endothelial growth factor signaling, and decreased expression of endothelial genes critical for vascular development, including vascular endothelial growth factor receptors Flt1 and Flk1, Pdgfb, Pecam1, CD34, integrin \u03b23, ephrin B2, Tie2, and the noncoding RNA Fendrr. Chromatin immunoprecipitation assay demonstrated that Flt1, Flk1, Pdgfb, Pecam1, and Tie2 genes are direct transcriptional targets of FOXF1.",
            "output": [
                "Is fOXF1 transcription factor required for formation of embryonic vasculature by regulating VEGF signaling in endothelial cells?"
            ]
        },
        {
            "id": "task847-a487fe4a174349d1adc787ff391286a4",
            "input": "To determine the effect of ketamine on the apoptosis of human uroepithelial cells (SVHUC-1) and the pathogenesis of ketamine-associated cystitis.', 'SV-HUC-1 cells were cultured under various concentrations of ketamine and differenttime. Flow cytometry was used to analyze the rate of cell apoptosis. The protein levels of Bax, Bcl-2, pro-caspase-3, and cleaved caspase-3 were detected by Western blot.', 'Compared with the control group, the apoptotic rate of ketamine cultured SV-HUC-1 cells increased. The expression of Bax increased, Bcl-2 expression decreased, and Bax/Bcl-2 in the ketamine cultured SV-HUC-1 cells was significantly higher. The protein level of pro-caspase-3 was significantly lower, and that of cleaved caspase-3 was significantly higher than that in the control group (P<0.05), positively correlated with the dose of ketamine and time of culture (P<0.05).",
            "output": [
                "Does [ Ketamine induce apoptosis of human uroepithelial SV-HUC-1 cells ]?"
            ]
        },
        {
            "id": "task847-2bf61613bb0f4c9e83d14c3cf8bb654b",
            "input": "Cerebrovascular accidents (CVAs) frequently coexist with coronary artery disease (CAD) and adversely affect prognosis in patients with CAD; however, fewer studies have investigated the role of prior ischemic stroke on the outcomes of percutaneous coronary intervention (PCI). The aim of this study was to determine the safety and effectiveness of PCI in patients with a prior ischemic stroke.', 'A review of patients who underwent PCI between June 2003 and September 2005 (n=3893) at the Beijing Anzhen Hospital of Capital University of Medical Science, identified 295 PCI patients with a prior ischemic stroke (\u2265 3 months) and 3598 patients without a prior stroke. To investigate whether prior history of an ischemic stroke was independently associated with increased risk of adverse PCI outcomes, prognostic parameters were analyzed using univariate analysis and Cox multivariate regression analysis. Propensity score analysis was then used to match the two subgroups of patients based on multiple factors known to impact cardiac outcome.', 'Patients with a prior ischemic stroke had more frequent high-risk baseline characteristics (diabetes, hypertension, hyperlipidemia and prior myocardial infarction). No significant differences were found in the major adverse cardiac and cerebrovascular event (MACCEs) rates between the two groups (1.7% in the stroke group vs. 1.4% in the non-stroke group; p=0.06). Diabetes mellitus, triple vessel CAD, number of diseased vessels, chronic total occlusion and previous myocardial infarction were independent predictors of MACCE in patients with prior stroke undergoing PCI.",
            "output": [
                "Is prior ischemic stroke associated with worse clinical outcomes in patients undergoing percutaneous coronary intervention?"
            ]
        },
        {
            "id": "task847-1b25591f755147cabe717935f9b05b78",
            "input": "Considerable variation in seed size commonly exists within plants, and is believed to be favoured under natural selection. This study aims to examine the extent to which seed size distribution depends on the presence of competing neighbour plants.', 'Phaseolus vulgaris plants rooting with or without a conspecific neighbour were grown in soil with high or low nutrient availability. Seeds were harvested at the end of the growth cycle, the total nitrogen and phosphorus invested in seed production were measured and within-plant seed size distribution was quantified using a set of statistical descriptors.', \"Exposure to neighbours' roots induced significant changes in seed size distribution. Plants produced proportionally more large seeds and fewer small ones, as reflected by significant increases in minimal seed size, mean seed size, skewness and Lorenz asymmetry coefficient. These effects were different from, and in several cases opposite to, the responses when the soil nutrient level was reduced, and were significant after correction for the amount of resources invested in seed production.",
            "output": [
                "Does the presence of a below-ground neighbour alter within-plant seed size distribution in Phaseolus vulgaris?"
            ]
        },
        {
            "id": "task847-92b9ff9fec274b7c84761e5a1bc4fb36",
            "input": "Photodynamic therapy (PDT) using aminolevulinic acid (ALA) with blue light or red light is effective for treating actinic keratoses (AKs). However, immunosuppression follows red light PDT, raising the spectre of skin cancer promotion in treated skin.', 'To determine whether broad-area short incubation (BASI)-ALA-PDT using blue light immunosuppression immunosuppresses treated skin.', 'Patients were evaluated clinically and by standardized facial biopsies of non-AK skin before, 24 hours and 1 month after customary blue light BASI-ALA-PDT. All biopsies were stained for markers of epidermal atypia and Langerhans cells (LCs); and at 24 hours to detect oxidative DNA damage.', 'Patients had an 81% reduction in AKs and slight improvement in clinical and histologic signs of photoaging after 1 month. The biopsied chronically photodamaged skin without clinically detectable AKs showed no effect of PDT on the LC number, distribution, or morphology; and no oxidative DNA damage, in contrast to the changes reported after customary red light PDT.",
            "output": [
                "Does effective blue light photodynamic therapy affect cutaneous langerhans cell number or oxidatively damage DNA?"
            ]
        },
        {
            "id": "task847-b9dea5b981484d37bf9ed14c11b53bc5",
            "input": "Tendon tissue engineering (TTE) tries to produce tendinous tissue of high quality to replace dysfunctional tissue. One possible application of TTE might be the replacement of ruptured tissue of the rotator cuff. Autologous tenocytes seem to be most suitable as no differentiation in vitro is necessary. Today it is still uncertain if there is a difference between tendon-derived cells (TDC) of different native tissues. Moreover, the search for suitable scaffolds is another important issue in TTE.', 'This study compared TDC of the long head of the biceps tendon (LHB), the anterior cruciate ligament (ACL) and the tendon of the musculus semitendinosus (TMS). The TDC were isolated using the cell migration method. Cell morphology was assessed using light microscopy and gene expression was performed using polymerase chain reaction (PCR). Afterwards, cell seeding efficiency and proliferation were tested on a collagen I scaffold using the WST-1 assay. Results were confirmed using H + E staining.', 'The TDC of the LHB showed higher expression levels of collagen type I and decorin (p < 0.01) compared to TDC of other origin. Results showed efficient cell seeding and proliferation within the scaffold. Proliferation within the scaffold was not as high as when cells were cultivated without a scaffold.",
            "output": [
                "Is the long head of the biceps tendon a suitable cell source for tendon tissue regeneration?"
            ]
        },
        {
            "id": "task847-6c3a4de92bc84e69ac3c4a98f5d3754d",
            "input": "Schizophrenia is a severe mental disorder affecting approximately 1% of the worldwide population. Yet, schizophrenia-like experiences (schizotypy) are very common in the healthy population, indicating a continuum between normal mental functioning and the psychosis found in schizophrenic patients. A continuum between schizotypy and schizophrenia would be supported if they share the same neurobiological origin. Two such neurobiological markers of schizophrenia are: (1) a reduction of sleep spindles (12-15 Hz oscillations during nonrapid eye movement sleep), likely reflecting deficits in thalamo-cortical circuits and (2) increased glutamine and glutamate (Glx) levels in the thalamus. Thus, this study aimed to investigate whether sleep spindles and Glx levels are related to schizotypal personality traits in healthy subjects.', 'Twenty young male subjects underwent 2 all-night sleep electroencephalography recordings (128 electrodes). Sleep spindles were detected automatically. After those 2 nights, thalamic Glx levels were measured by magnetic resonance spectroscopy. Subjects completed a magical ideation scale to assess schizotypy.', 'Sleep spindle density was negatively correlated with magical ideation (r = -.64, P < .01) and thalamic Glx levels (r = -.70, P < .005). No correlation was found between Glx levels in the thalamus and magical ideation (r = .12, P > .1).",
            "output": [
                "Are sleep spindles related to schizotypal personality traits and thalamic glutamine/glutamate in healthy subjects?"
            ]
        },
        {
            "id": "task847-9a21f5f67939421eb7c9d9cf2e43959f",
            "input": "Ductal carcinoma in situ with microinvasion (DCISM) is a rare diagnosis with a good prognosis. Although nodal metastases are uncommon, sentinel lymph node biopsy (SLNB) remains standard care. Volume of disease in invasive breast cancer is associated with SLNB positivity, and, thus we hypothesized that in a large cohort of patients with DCISM, multiple foci of microinvasion might be associated with a higher risk of positive SLNB.', 'Records from a prospective institutional database were reviewed to identify patients with DCISM who underwent SLNB between June 1997 and December 2010. Pathology reports were reviewed for number of microinvasive foci and categorized as 1 focus or \u22652 foci. Demographic, pathologic, treatment, and outcome data were obtained and analyzed.', 'Of 414 patients, 235 (57 %) had 1 focus of microinvasion and 179 (43 %) had \u22652 foci. SLNB macrometastases were found in 1.4 %, and micrometastases were found in 6.3 %; neither were significantly different between patients with 1 focus versus \u22652 foci (p = 1.0). Patients with positive SLNB or \u22652 foci of microinvasion were more likely to receive chemotherapy. At median 4.9 years (range 0-16.2 years) follow-up, 18 patients, all in the SLNB negative group, had recurred for an overall 5-year recurrence-free proportion of 95.9 %.",
            "output": [
                "Is extent of microinvasion in ductal carcinoma in situ associated with sentinel lymph node metastases?"
            ]
        },
        {
            "id": "task847-c02974fbe38a44dd8bef16207596b8c3",
            "input": "This open-label, prospective, observational study aimed to evaluate treatment response, efficacy therapy and safety to IFN \u03b1-2b for the essential thrombocythemia (ET) and polycythemia vera (PV) with JAK2V617F positive mutation.', 'A total of 123 ET patients received IFN\u03b1-2b therapy with JAK2V617F positive or negative mutation; and 136 PV patients with JAK2V617F(+) received IFN\u03b1-2b or hydroxyurea (HU) therapy according to random number assignment (ages 18-65 years old).', 'ET patients receiving IFN \u03b1-2b with JAK2V617F(+) had a greater advantage in overall hematologic response (OHR) than JAK2V617F(-) (83.3% versus 61.4%, P<0.01). For PV patients with JAK2V617F(+), IFN had no OHR superiority to HU (70.3% versus 70.8%, P>0.05), but which gained a greater satisfactory molecular response than HU (54.7% versus 19.4%, P<0.01). IFN significantly decreased the phlebotomy rate, which was better than HU for MPDs patients with OHR than HU (3.6% versus 65.7%, P<0.01). Furthermore, ET patients with JAK2V617F(+) demonstrated a definite advantage over JAK2V617F(-) in five-year PFS (75.9% versus 47.6%, P<0.05). For PV patients with JAK2V617F(+), IFN \u03b1-2b was superior to HU in five-year PFS (66.3% versus 46.7%, P<0.01). Moreover, IFN \u03b1-2b also contributed to improved vasomotor symptoms in MPDs, and especially significantly decreased the incidence of distal paresthesias (14.1% versus 37.5%) and erythromelalgia (9.4% versus 29.2%) better than HU (P<0.01). Meanwhile, IFN did not observe the severe hematological adverse events in patients with PV or ET.",
            "output": [
                "Does interferon \u03b1-2b gain high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation?"
            ]
        },
        {
            "id": "task847-bbe8e31f79f342acb055fca0c32d7986",
            "input": "Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor.', 'In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs.', 'We present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen, we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is required for its reactive oxygen species-induced nuclear translocation. FOXO4 does not interact with IPO7 or IPO8.",
            "output": [
                "Does evolutionary acquisition of cysteines determine FOXO paralog-specific redox signaling?"
            ]
        },
        {
            "id": "task847-475eaaeeb11b419591c1a7e0b8e14422",
            "input": "To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC).', 'One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival.', 'Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (\u2264 72/>72), carcinoembryonic antigen (\u2264 20/>20) (ng/ml), white blood cell count (\u2264 9.5/>9.5) (\u00d7 10(3)/mm(3)), prognostic nutritional index (PNI) (\u2264 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (\u2264 45) (p<0.001).",
            "output": [
                "Is prognostic nutritional index associated with survival after total gastrectomy for patients with gastric cancer?"
            ]
        },
        {
            "id": "task847-90368fdbab4d4213bb6b5e8d2ec5c775",
            "input": "Matrix Metalloproteinase-26 (MMP-26) is the smallest member of matrix metalloproteinase (MMP) family that functions mainly in the extracellular milieu to cleave the extracellular matrix proteins. It is expressed in various cell types of placenta, but its function in placentation has been poorly understood. Considering the existence of a unique cysteine switch sequence in MMP-26 protein sequence, as well as the evidence in cancer cells indicating the digestion of the NH2-terminal domain of ER\u03b2 by MMP-26, we hypothesize that MMP-26 may have specific intracellular activity in human placental trophoblast cells.', 'This study aimed to identify the intracellular binding partners of MMP-26 and investigate how MMP-26 is involved in placentation through the interactions with its partners.', 'Yeast two-hybrid system was employed to screen potential binding partners of MMP-26 in human placenta. Immunoprecipitation and immunofluorescence assays were conducted to verify the interactions between MMP-26 and the binding partners. HEK293T and HTR8/SVneo cell lines were used as in vitro models to investigate the roles of the interaction between MMP-26 and its binding partner on cell behaviors.', 'RESULTS of yeast two-hybrid assay, immunoprecipitation, and immunofluorescence assays revealed that MMP-26 could bind to growth differentiation factor 15 (GDF15) in the intracellular milieu. The binding of MMP-26 to GDF15 was responsible for the processing and maturation of pro-GDF15, and the process was dependent on the enzymatic activity of MMP-26. In human placental trophoblast cells, MMP-26 could facilitate the pro-apoptotic effect of GDF15.",
            "output": [
                "Does maturation of growth differentiation factor 15 in human placental trophoblast cells depend on the interaction with Matrix Metalloproteinase-26?"
            ]
        },
        {
            "id": "task847-01f8925088db4f28adbec4f4c5d2aee1",
            "input": "The enzyme extracellular superoxide dismutase (EC-SOD; SOD3) is a major antioxidant defense in lung and vasculature. A nonsynonomous single-nucleotide polymorphism in EC-SOD (rs1799895) leads to an arginine to glycine amino acid substitution at position 213 (R213G) in the heparin-binding domain. In recent human genetic association studies, this single-nucleotide polymorphism attenuates the risk of lung disease, yet paradoxically increases the risk of cardiovascular disease.', 'Capitalizing on the complete sequence homology between human and mouse in the heparin-binding domain, we created an analogous R213G single-nucleotide polymorphism knockin mouse. The R213G single-nucleotide polymorphism did not change enzyme activity, but shifted the distribution of EC-SOD from lung and vascular tissue to extracellular fluid (eg, bronchoalveolar lavage fluid and plasma). This shift reduces susceptibility to lung disease (lipopolysaccharide-induced lung injury) and increases susceptibility to cardiopulmonary disease (chronic hypoxic pulmonary hypertension).",
            "output": [
                "Does a common polymorphism in extracellular superoxide dismutase affect cardiopulmonary disease risk by altering protein distribution?"
            ]
        },
        {
            "id": "task847-a5ab0015b07d484b864bd929278c8e07",
            "input": "Research has shown that hand gestures affect comprehension and production of speech at semantic, syntactic, and pragmatic levels for both native language and second language (L2). This study investigated a relatively less explored question: Do hand gestures influence auditory learning of an L2 at the segmental phonology level?', 'To examine auditory learning of phonemic vowel length contrasts in Japanese, 88 native English-speaking participants took an auditory test before and after one of the following 4 types of training in which they (a) observed an instructor in a video speaking Japanese words while she made syllabic-rhythm hand gesture, (b) produced this gesture with the instructor, (c) observed the instructor speaking those words and her moraic-rhythm hand gesture, or (d) produced the moraic-rhythm gesture with the instructor.', 'All of the training types yielded similar auditory improvement in identifying vowel length contrast. However, observing the syllabic-rhythm hand gesture yielded the most balanced improvement between word-initial and word-final vowels and between slow and fast speaking rates.",
            "output": [
                "Does effects of hand gestures on auditory learning of second-language vowel length contrast?"
            ]
        },
        {
            "id": "task847-f6fd9a2a56ca4bdd9b01d912c7f46d26",
            "input": "Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice.', 'DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs).', 'At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial.",
            "output": [
                "Does next-generation sequencing of adrenocortical carcinoma reveal new routes to targeted therapies?"
            ]
        },
        {
            "id": "task847-50c15cba8187430aaf2e1e162aca9f40",
            "input": "Endothelial dysfunction and hypertension is more common in individuals with diabetes than in the general population. This study was aimed to investigate the underlying mechanisms responsible for endothelial dysfunction of type 1 diabetic rats fed with high-salt diet.', 'Type 1 diabetes (DM) was induced by intraperitoneal injection of streptozotocin (70 mg\u00b7kg(-1)). Normal or diabetic rats were randomly fed high-salt food (HS, 8% NaCl) or standard food (CON) for 6 weeks.', 'Both HS (143\u00b110 mmHg) and DM+HS (169\u00b111 mmHg) groups displayed significantly higher systolic blood pressure than those in the CON group (112\u00b112 mmHg, P<0.01). DM+HS rats exhibited more pronounced impairment of vasorelaxation to acetylcholine and insulin compared with either DM or HS. Akt/endothelial nitric oxide synthase (eNOS) phosphorylation levels and nitric oxide (NO) concentration in DM+HS were significantly lower than in DM. The levels of caveolin-1 (cav-1) in DM+HS were significantly higher than that in DM and HS. Co-immunoprecipitation results showed increased interaction between cav-1 and eNOS in the DM+HS group. In the presence of cav-1 small interfering RNA (siRNA), eNOS phosphorylations in human umbilical vein endothelial cells (HUVEC) were significantly increased compared with control siRNA. Cav-1 was slightly but not significantly lower in HUVEC cultured with high glucose and high-salt buffer solution and pretreated with wortmannin or l-nitro-arginine methyl ester.",
            "output": [
                "Does upregulation of caveolin-1 contribute to aggravated high-salt diet-induced endothelial dysfunction and hypertension in type 1 diabetic rats?"
            ]
        },
        {
            "id": "task847-a4c92f9770224fcaa0177240339367d1",
            "input": "The IL-1 family of cytokines is known to play an important role in inflammation therefore understanding the mechanism by which they are produced is paramount. Despite the recent plethora of publications dedicated to the study of these cytokines, the mechanism by which they are produced in the airway following endotoxin, Lipopolysaccharide (LPS), exposure is currently unclear. The aim was to determine the mechanism by which the IL-1 cytokines are produced after LPS inhaled challenge.', 'Mice were challenged with aerosolised LPS, and lung tissue and bronchiolar lavage fluid (BALF) collected. Targets were measured at the mRNA and protein level; caspase activity was determined using specific assays.', 'BALF IL-1b/IL-18, but not IL-1a, was dependent on Ice Protease-Activating Factor (IPAF), and to a lesser extent Apoptosis-associated Speck-like protein containing a CARD (ASC). Interestingly, although we measured an increase in mRNA expression for caspase 1 and 11, we could not detect an increase in lung enzyme activity or a role for them in IL-1a/b production. Further investigations showed that whilst we could detect an increase in caspase 8 activity at later points in the time course (during resolution of inflammation), it appeared to play no role in the production of IL-1 cytokines in this model system.",
            "output": [
                "Does tLR4 activation induce IL-1\u03b2 release via an IPAF dependent but caspase 1/11/8 independent pathway in the lung?"
            ]
        },
        {
            "id": "task847-87ffc6e8425947208eef5f313afc5805",
            "input": "Numerous studies have reported the association between ambient temperature and mortality. However, few studies have focused on the effects of extreme temperatures on diabetes mortality, particularly in China. The objective of the present study was to assess the effects of extremely cold and hot temperatures on diabetes mortality in urban areas of Harbin and Chongqing in China to provide scientific evidence for public health policy implementation to respond to challenges in diabetes mortality because of extreme temperature events.', 'A double threshold B-spline distributed lag non-linear model (DLNM) was used to investigate the effects of extremely cold and hot temperatures on diabetes mortality from lag 0 to 30 days, after controlling for potential confounders including air pollutants. The unit risk, which is the elevated cumulative risk of diabetes mortality caused by each 1 \u00b0C change in extremely cold and hot temperatures during certain lag days, was estimated for extreme cold and heat using simple regression analysis.', 'Significant associations between both extreme hot and cold temperatures and diabetes mortality were observed in Harbin and Chongqing for different lag lengths. In Harbin, the extreme cold effects on diabetes mortality were delayed by three days and lasted for six days (lag 3-8), with the highest risk (RR 95% CI: 1.223,1.054-1.418 for -23 \u00b0C) at lag 5. The hot effects were delayed one day and lasted for three days (lag 1-3), with the peak RR (1.343: 1.080-1.670 for 37 \u00b0C) at lag 2. In Chongqing, the cold effects on diabetes mortality were delayed by seven days and lasted for four days (lag 7-10), with the highest risk (1.201: 1.006-1.434 for 4 \u00b0C) at lag 7. The hot effects peaked (1.811: 1.083-3.027 for 41 \u00b0C) at lag 0 and lasted for 2 days (lag 0-1). The unit risk for cold and hot effects was 12.9% (95% CI: 2.5-33.7%) and 16.5% (95% CI: 3.8-39.1%) in Harbin and 12.5% (95% CI: -4.7 to 47.5%) and 19.7% (95% CI: 3.9-48.5%) in Chongqing, respectively.",
            "output": [
                "Do extremely cold and hot temperatures increase the risk of diabetes mortality in metropolitan areas of two Chinese cities?"
            ]
        },
        {
            "id": "task847-9f2ea4caa0ae4afd91d0db8a3f88e456",
            "input": "Tumor-derived matricellular proteins such as osteopontin (OPN) and tenascin-C (TN-C) have been implicated in tumor growth and metastasis. However, the molecular basis of how these proteins contribute to tumor progression remains to be elucidated. Importantly, these matricellular proteins are known to interact with \u03b19\u03b21 integrin. Therefore, we hypothesized that tumor-derived \u03b19\u03b21 integrin may contribute to tumor progression. To clarify the roles of \u03b19\u03b21 integrin in tumor growth and lymphatic metastasis, we used an inhibitory anti-human \u03b19\u03b21 integrin antibody (anti-h\u03b19\u03b21 antibody) and a \u03b19\u03b21 integrin-positive human breast cancer cell line, MDA-MB-231 luc-D3H2LN (D3H2LN), in vitro functional assays, and an in vivo orthotopic xenotransplantation model. In this study, we demonstrated that tumor, but not host \u03b19\u03b21 integrin, contributes to tumor growth, lymphatic metastasis, recruitment of cancer-associated fibroblasts (CAFs), and host-derived OPN production. We also found that CAFs contributed to tumor growth, lymphatic metastasis, and host-derived OPN levels. Consistent with those findings, tumor volume was well-correlated with numbers of CAFs and levels of host-derived OPN. Furthermore, it was shown that the inoculation of D3H2LN cells into mammary fat pads with mouse embryonic fibroblasts (MEFs), obtained from wild type, but not OPN knock-out mice, resulted in enhancement of tumor growth, thus indicating that CAF-derived OPN enhanced tumor growth. These results suggested that tumor \u03b19\u03b21-mediated signaling plays a pivotal role in generating unique primary tumor tissue microenvironments, which favor lymphatic metastasis and tumor growth.",
            "output": [
                "Does tumor-\u03b19\u03b21 integrin-mediated signaling induce breast cancer growth and lymphatic metastasis via the recruitment of cancer-associated fibroblasts?"
            ]
        },
        {
            "id": "task847-41ff3b9d24cd422992c0b61236ca1c61",
            "input": "The global effort to annotate the non-coding portion of the human genome relies heavily on chromatin immunoprecipitation data generated with high-throughput DNA sequencing (ChIP-seq). ChIP-seq is generally successful in detailing the segments of the genome bound by the immunoprecipitated transcription factor (TF), however almost all datasets contain genomic regions devoid of the canonical motif for the TF. It remains to be determined if these regions are related to the immunoprecipitated TF or whether, despite the use of controls, there is a portion of peaks that can be attributed to other causes.', \"Analyses across hundreds of ChIP-seq datasets generated for sequence-specific DNA binding TFs reveal a small set of TF binding profiles for which predicted TF binding site motifs are repeatedly observed to be significantly enriched. Grouping related binding profiles, the set includes: CTCF-like, ETS-like, JUN-like, and THAP11 profiles. These frequently enriched profiles are termed 'zingers' to highlight their unanticipated enrichment in datasets for which they were not the targeted TF, and their potential impact on the interpretation and analysis of TF ChIP-seq data. Peaks with zinger motifs and lacking the ChIPped TF's motif are observed to compose up to 45% of a ChIP-seq dataset. There is substantial overlap of zinger motif containing regions between diverse TF datasets, suggesting a mechanism that is not TF-specific for the recovery of these regions.",
            "output": [
                "Are non-targeted transcription factors motifs a systemic component of ChIP-seq datasets?"
            ]
        },
        {
            "id": "task847-4a700e2ef3cd4e248f926616ab0c3a63",
            "input": "Infants born preterm commonly suffer from a combination of hypoxia-ischemia (HI) and infectious perinatal inflammatory insults that lead to cerebral palsy, cognitive delay, behavioral issues and epilepsy. Using a novel rat model of combined late gestation HI and lipopolysaccharide (LPS)-induced inflammation, we tested our hypothesis that inflammation from HI and LPS differentially affects gliosis, white matter development and motor impairment during the first postnatal month.', 'Pregnant rats underwent laparotomy on embryonic day 18 and transient systemic HI (TSHI) and/or intra-amniotic LPS injection. Shams received laparotomy and anesthesia only. Pups were born at term. Immunohistochemistry with stereological estimates was performed to assess regional glial loads, and western blots were performed for protein expression. Erythropoietin ligand and receptor levels were quantified using quantitative PCR. Digigait analysis detected gait deficits. Statistical analysis was performed with one-way analysis of variance and post-hoc Bonferonni correction.', 'Microglial and astroglial immunolabeling are elevated in TSHI + LPS fimbria at postnatal day 2 compared to sham (both P < 0.03). At postnatal day 15, myelin basic protein expression is reduced by 31% in TSHI + LPS pups compared to shams (P < 0.05). By postnatal day 28, white matter injury shifts from the acute injury pattern to a chronic injury pattern in TSHI pups only. Both myelin basic protein expression (P < 0.01) and the phosphoneurofilament/neurofilament ratio, a marker of axonal dysfunction, are reduced in postnatal day 28 TSHI pups (P < 0.001). Erythropoietin ligand to receptor ratios differ between brains exposed to TSHI and LPS. Gait analyses reveal that all groups (TSHI, LPS and TSHI + LPS) are ataxic with deficits in stride, paw placement, gait consistency and coordination (all P < 0.001).",
            "output": [
                "Does complex pattern of interaction between in utero hypoxia-ischemia and intra-amniotic inflammation disrupt brain development and motor function?"
            ]
        },
        {
            "id": "task847-11e709ee87fb42e78dc3e9516ed07766",
            "input": "Arteriogenesis represents the maturation of preformed vascular connections in response to flow changes and shear stress. These collateral vessels can restore up to 60% of the native blood flow. Shear stress and vascular injury can induce the release of nucleotides from vascular smooth muscle cells and platelets that can serve as signaling ligands, suggesting they may be involved in mediating arteriogenesis. The P2Y2 nucleotide receptor (P2Y2R) has also been shown to mediate smooth muscle migration and arterial remodeling. Thus, we hypothesize that P2Y2R mediates arteriogenesis in response to ischemia.', 'Hind limb ischemia was induced by femoral artery ligation (FAL) in C57Bl/6NJ or P2Y2R negative mice (P2Y2(-/-)). Hind limb perfusion was measured with laser Doppler perfusion imaging and compared with the sham-operated contralateral limb immediately and at 3, 7, 14, 21, and 28 days after ligation. Collateral vessel size was measured by Microfil casting. Muscle specimens were harvested and analyzed with immunohistochemistry for Ki67, vascular cell adhesion molecule, macrophages, and muscle viability by hematoxylin and essoin stain.', 'Hind limb ischemia induced by FAL in C57Bl/6NJ mice resulted in significant ischemia as measured by laser Doppler perfusion imaging. There was rapid recovery to nearly normal levels of perfusion by 2 weeks. FAL in P2Y2(-/-) mice resulted in severe ischemia with greater tissue loss. Recovery of perfusion was impaired, achieving only 40% compared with wild-type mice by 28 days. Collateral vessels in the P2Y2(-/-) mice were underdeveloped, with reduced vascular cell proliferation and smaller vessel size. The collaterals were \u223c65% the size of wild-type collateral vessels (P = .011). Angiogenesis at 28 days in the ischemic muscle, however, was greater in the P2Y2(-/-) mice (P < .001), possibly related to persistent ischemia leading and angiogenic drive. Early macrophage recruitment was reduced by nearly 70% in P2Y2(-/-) despite significantly more myocyte necrosis. However, inflammation was greater at 28 days in the P2Y2(-/-) mice.",
            "output": [
                "Does p2Y2 nucleotide receptor mediate arteriogenesis in a murine model of hind limb ischemia?"
            ]
        },
        {
            "id": "task847-6b1678d1a8244120a3611b4c73946136",
            "input": "Sphingolipid metabolism is altered in diabetes and we analyzed the plasma concentrations of sphingolipid species to investigate their association with the development of albuminuria in type 1 patients with diabetes.', 'Samples were collected from 497 type 1 diabetic patients during their enrollment into the Diabetes Control and Complications Trial (DCCT). We determined plasma concentrations of multiple ceramide species and individual sphingoid bases and their phosphates using high performance liquid chromatography-tandem mass spectrometry and investigated their association with the development of albuminuria during 14-20 years of follow-up.', 'Patients exhibited normal albumin excretion rates (AER <40 mg/24h) at the time of plasma sampling. Although the majority of patients (N = 291; 59%) exhibited normal levels of albuminuria throughout follow-up, 141 patients (28%) progressed to microalbuminuria (40 mg/24h \u2264 AER<300 mg/24h), while 65 (13%) progressed to macroalbuminuria (AER \u2265 300 mg/24h). To test the association of log transformed plasma sphingolipid level with the development of albuminuria, generalized logistic regression models were used where normal, micro- and macroalbuminuria were the outcomes of interest. Models were adjusted for DCCT treatment group, baseline retinopathy, gender, baseline HbA1c %, age, AER, lipid levels, diabetes duration, and the use of ACE/ARB drugs. Increased plasma levels of very long, but not long chain ceramide species measured at DCCT baseline were associated with decreased odds to develop macroalbuminuria during the subsequent nineteen years (DCCT Baseline to EDIC year 8).",
            "output": [
                "Are decreased plasma levels of select very long chain ceramide species associated with the development of nephropathy in type 1 diabetes?"
            ]
        },
        {
            "id": "task847-139d519fc8614e27b953f137d53f7ca8",
            "input": "Baseline carbohydrate antigen 19-9 (CA 19-9) is a useful prognostic marker in pancreatic ductal adenocarcinoma (PDA); however, data on the significance of a change in CA 19-9 following neoadjuvant therapy are lacking.', \"All patients receiving neoadjuvant therapy for PDA from July 2010 to February 2013 were retrospectively reviewed. Resection rate, R0 resection rate, need for venous resection, and overall survival were correlated to CA 19-9 response. Fisher's exact test, Kaplan-Meier survival analysis, and multivariate analysis using Cox regression were used.\", 'A total of 78 patients were studied (21 patients with resectable disease, 40 borderline resectable, and 17 with locally advanced disease). A variety of chemotherapies \u00b1 radiation were utilized during the study period. Overall, 56 patients (72 %) had a decrease in CA 19-9 of >50 % with neoadjuvant treatment. In borderline resectable patients, CA 19-9 response of >50 % predicted R0 resection (odds ratio 4.2; p = 0.05). In borderline resectable patients who had an increase in CA 19-9, none of five (0 %) underwent R0 resection compared with 80 % of the remaining cohort (p = 0.001). The complete pathologic response rate was 29 % in patients who had a CA 19-9 response of >90 % versus 0 % in the remaining patients (p < 0.001). A CA 19-9 response of >50 % resulted in improved overall survival (28.0 vs. 11.1 months; p < 0.0001) and was an independent predictor of survival (hazard ratio 0.26; 95 % CI 0.13-0.55; p < 0.0001).",
            "output": [
                "Is serum CA 19-9 response to neoadjuvant therapy associated with outcome in pancreatic adenocarcinoma?"
            ]
        },
        {
            "id": "task847-01361b3c6dfa494aa42b3c840a4398c3",
            "input": "Cancer stromal fibroblasts are important members of the cancer microenvironment. In this study, we determined the effect of sunitinib, a small molecule tyrosine kinase inhibitor, on the primary human colonic fibroblasts.', 'Cell cycle analysis and cell proliferation assays were performed to evaluate the inhibitory effect of sunitinib in vitro. Western-blot analysis was performed to evaluate variations in the levels of phosphorylated platelet-derived growth factor receptor \u03b2 (PDGFR-\u03b2), Akt, and ERK proteins. Co-injection of SW620 cells and colonic fibroblasts in nude mice was employed to test anti-growth efficacy in vivo.', 'Sunitinib was found to effectively inhibit the growth of primary colonic fibroblasts. Low-dose sunitinib blocked the PDGF-BB-induced cell proliferation and PDGFR-\u03b2 signaling. Co-injection of SW620 cells and colonic fibroblasts in nude mice generated greater tumor volumes than single injection of SW620 cells. Sunitinib treatment inhibited the SW620 cell+colonic fibroblast tumor growth more effectively than treatment of 5-fluorouracil.",
            "output": [
                "Does sunitinib mesylate inhibit proliferation of human colonic stromal fibroblasts in vitro and in vivo?"
            ]
        },
        {
            "id": "task847-6993935530c4425d8a43f6a71f447fa4",
            "input": "Little is known about the short-term and long-term sequelae of concussion, and about when athletes who have sustained such injuries can safely return to play.', 'To examine whether sports-related concussion increases the risk of subsequent injury in elite male football players.', 'Prospective cohort study.', 'Injuries were registered for 46 male elite football teams in 10 European countries in the 2001/2002-2011/2102 seasons. Two survival models were used to analyse whether concussion increased the subsequent risk of an injury in the first year.', 'During the follow-up period, 66 players sustained concussions and 1599 players sustained other injuries. Compared with the risk following other injuries, concussion was associated with a progressively increased risk of a subsequent injury in the first year (0 to <3\\u2005months, HR=1.56, 95% CI 1.09 to 2.23; 3 to <6\\u2005months, HR=2.78, 95% CI 1.58 to 4.89; 6-12\\u2005months, HR=4.07, 95% CI 2.14 to 7.76). In the second model, after adjustment for the number of injuries in the year preceding the concussion, this injury remained significantly associated with the risk of subsequent injury in the first year (HR=1.47, 95% CI 1.05 to 2.05).",
            "output": [
                "Does sports-related concussion increase the risk of subsequent injury by about 50 % in elite male football players?"
            ]
        },
        {
            "id": "task847-574610691f5a4ae98384ebf66c380ce6",
            "input": "To investigate whether intracavitary physiotherapy is superior to endometrial scratching in patients with recurrent implantation failure (RIF) after in vitro fertilization/intracytoplasmic sperm injection- embryo transfer (IVF/ICSI-ET) cycles.', 'According to the inclusion criteria defined by our hospital, 63 patients with RIF were included in the retrospective study. 20 patients who received intracavitary physiotherapy were classified into Group A, 8 patients with both intracavitary physiotherapy and endometrial scratching were into Group B, and 35 patients who underwent endometrial scratching were into Group C. The primary outcome measures were implantation and clinical pregnancy rates. The secondary outcome measure was pregnancy outcome.', 'There were no statistical differences in implantation and clinical pregnancy rates between Groups A and C (29.41 vs 35.59 %, 45.00 vs 48.57 % respectively, P > 0.05), Groups B and C (36.36 vs 35.59 %, 50.00 vs 48.57 % respectively, P > 0.05). In addition, no statistical differences were discovered in pregnancy outcomes between Groups A and C (P > 0.05), Groups B and C (P > 0.05).",
            "output": [
                "Is intracavitary physiotherapy inferior to endometrial scratching in patients with recurrent implantation failure?"
            ]
        },
        {
            "id": "task847-9685ba5fef6840b199c19cfeb5652d8d",
            "input": "Approximately 40% of adults develop invasive cancer during their lifetimes, many of whom require chemotherapy. Herpes zoster (HZ) is common and often severe in patients undergoing chemotherapy, yet there are no data regarding whether these patients retain specific protection against HZ if they had previously received zoster vaccine. We conducted a study to determine whether zoster vaccine was effective in patients who subsequently underwent chemotherapy.', 'The cohort study consisted of Kaiser Permanente Southern California members aged \u226560 years treated with chemotherapy. The exposure variable was receipt of zoster vaccine prior to initiation of chemotherapy. Incident HZ cases were identified using International Classification of Diseases, Ninth Revision diagnostic codes. HZ incidence rates were calculated; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models.', 'There were 91 and 583 HZ cases in the vaccinated and unvaccinated cohorts, respectively, yielding an incidence rate of 12.87 (95% CI, 10.48-15.80) vs 22.05 (95% CI, 20.33-23.92) per 1000 person-years. Thirty-month cumulative incidence was 3.28% in the vaccinated group and 5.34% in the unvaccinated group (P < .05). The adjusted HR for HZ was 0.58 (95% CI, .46-.73) and showed no significant variation by age, sex, or race. HZ incidence rates remained increased in the small subgroup of persons receiving zoster vaccine within 60 days before chemotherapy, but this was the only group affected by indication bias. No vaccinated patients underwent hospitalization for HZ, compared with 6 unvaccinated patients.",
            "output": [
                "Does vaccination against zoster remain effective in older adults who later undergo chemotherapy?"
            ]
        },
        {
            "id": "task847-84c54a1ced664e198771a633e0501359",
            "input": "Obesity is a well-known risk factor for type 2 diabetes. Genome-wide association studies have identified a number of genetic loci associated with obesity. The aim of this study is to examine the contribution of obesity-related genomic loci to type 2 diabetes in a Chinese population.', 'We successfully genotyped 18 obesity-related single nucleotide polymorphisms among 5338 type 2 diabetic patients and 4663 controls. Both individual and joint effects of these single nucleotide polymorphisms on type 2 diabetes and quantitative glycemic traits (assessing \u03b2-cell function and insulin resistance) were analyzed using logistic and linear regression models, respectively.', 'Two single nucleotide polymorphisms near MC4R and GNPDA2 genes were significantly associated with type 2 diabetes before adjusting for body mass index and waist circumference (OR (95% CI)\\u200a=\\u200a1.14 (1.06, 1.22) for the A allele of rs12970134, P\\u200a=\\u200a4.75\u00d710(-4); OR (95% CI)\\u200a=\\u200a1.10 (1.03, 1.17) for the G allele of rs10938397, P\\u200a=\\u200a4.54\u00d710(-3)). When body mass index and waist circumference were further adjusted, the association of MC4R with type 2 diabetes remained significant (P\\u200a=\\u200a1.81\u00d710(-2)) and that of GNPDA2 was attenuated (P\\u200a=\\u200a1.26\u00d710(-1)), suggesting the effect of the locus including GNPDA2 on type 2 diabetes may be mediated through obesity. Single nucleotide polymorphism rs2260000 within BAT2 was significantly associated with type 2 diabetes after adjusting for body mass index and waist circumference (P\\u200a=\\u200a1.04\u00d710(-2)). In addition, four single nucleotide polymorphisms (near or within SEC16B, BDNF, MAF and PRL genes) showed significant associations with quantitative glycemic traits in controls even after adjusting for body mass index and waist circumference (all P values<0.05).",
            "output": [
                "Are obesity-related genomic loci associated with type 2 diabetes in a Han Chinese population?"
            ]
        },
        {
            "id": "task847-68538cea5f29457891337cb84638aa1d",
            "input": "Photodynamic therapy (PDT) is linked with oxidative damage of biomolecules causing significant impairment of essential cellular functions that lead to cell death. It is the reason why photodynamic therapy has found application in treatment of different oncological, cardiovascular, skin and eye diseases. Efficacy of PDT depends on combined action of three components; sensitizer, light and oxygen. In the present study, we examined whether higher partial pressure of oxygen increases lethality in HeLa cell lines exposed to light in the presence of chloraluminium phthalocyanine disulfonate (ClAlPcS2).', 'ClAlPcS2- sensitized HeLa cells incubated under different oxygen conditions were exposed to PDT. Production of singlet oxygen ((1)O2) and other forms of reactive oxygen species (ROS) as well as changes in mitochondrial membrane potential were determined by appropriately sensitive fluorescence probes. The effect of PDT on HeLa cell viability under different oxygen conditions was quantified using the standard methylthiazol tetrazolium (MTT) test.', 'At the highest oxygen concentration of 28 \u00b1 2 mg/l HeLa cells were significantly more sensitive to light-activated ClAlPcS2 (EC50=0.29 \u00b1 0.05 \u03bcM) in comparison to cells incubated at lower oxygen concentrations of 8 \u00b1 0.5 and 0.5 \u00b1 0.1 mg/l, where the half maximal effective concentration was 0.42 \u00b1 0.06 \u03bcM and 0.94 \u00b1 0.14 \u03bcM, respectively. Moreover, we found that the higher presence of oxygen is accompanied with higher production of singlet oxygen, a higher rate of type II photodynamic reactions, and a significant drop in the mitochondrial membrane potential.",
            "output": [
                "Does high oxygen partial pressure increase photodynamic effect on HeLa cell lines in the presence of chloraluminium phthalocyanine?"
            ]
        },
        {
            "id": "task847-0da62a3316c145aeab3c7e430d809ae8",
            "input": "Lynch syndrome (LS) is clinically defined by the Amsterdam criteria (AC) and by germline mutations in mismatch-repair (MMR) genes leading to microsatellite instability (MSI) at the molecular level. Patients who do not fulfil AC are considered suspected-Lynch according to the less stringent Bethesda guidelines (BG) and should be tested for MSI and MMR germline mutations. BRAF mutations have been proposed as a marker to exclude LS because they are generally absent in LS patients and present in sporadic colorectal cancer (sCRC) with MSI due to promoter hypermethylation of the MLH1 gene. Our aim was to verify whether BRAF mutations may improve the criteria to select patients for germline MMR mutation assessment.', 'We analyzed 303 formalin-fixed paraffin-embedded CRC samples including 174 sCRC, 28 patients fulfilling AC, and 101 suspected-Lynch patients fulfilling BG. We analyzed MSI and BRAF mutations in all CRC samples. MLH1, MSH2 and MSH6 germline mutations were investigated in MSI patients fulfilling AC or BG.', 'sCRC samples showed MSI in 20/174 (11%) cases. BRAF mutations were detected in 10/174 (6%) sCRC cases and were significantly correlated with MSI (P = 0.002). MSI was observed in 24/28 (86%) Amsterdam cases which were BRAF wild-type. MMR gene mutation was detected in 22/26 (85%) AC cases, all showing MSI. Suspected-Lynch cases carried MSI in 41/101 (40%) and BRAF mutations in 7/101 (7%) cases. MMR gene mutation was detected in 13/28 (46%) evaluable MSI patients of this group and only in cases characterized by a wild-type BRAF gene.",
            "output": [
                "Is bRAF mutation analysis a valid tool to implement in Lynch syndrome diagnosis in patients classified according to the Bethesda guidelines?"
            ]
        },
        {
            "id": "task847-008380a570d24591bcb7946c8548e6f9",
            "input": "To design and synthesize a library of structurally related, small molecules related to homologues of compounds produced by the plant Petiveria alliacea and determine their ability to interfere with AI-2 cell-cell communication and biofilm formation by oral bacteria. Many human diseases are associated with persistent bacterial biofilms. Oral biofilms (dental plaque) are problematic as they are often associated with tooth decay, periodontal disease and systemic disorders such as heart disease and diabetes.', 'Using a microplate-based approach, a bio-inspired small molecule library was screened for anti-biofilm activity against the oral species Streptococcus mutans UA159, Streptococcus sanguis 10556 and Actinomyces oris MG1. To complement the static screen, a flow-based BioFlux microfluidic system screen was also performed under conditions representative of the human oral cavity. Several compounds were found to display biofilm inhibitory activity in all three of the oral bacteria tested. These compounds were also shown to inhibit bioluminescence by Vibrio harveyi and were thus inferred to be quorum sensing (QS) inhibitors.",
            "output": [
                "Do s-aryl-L-cysteine sulphoxides and related organosulphur compounds alter oral biofilm development and AI-2-based cell-cell communication?"
            ]
        },
        {
            "id": "task847-0f2d6ddd72284608b87d81739c942a70",
            "input": "This study aims to assess whether the associations between burnout and sick leave due to stress-related mental disorders, other mental disorders, and somatic conditions are influenced by familial (genetic and shared environmental) factors.', 'In this prospective cohort study, 23,611 Swedish twins born between 1959 and 1985, who answered a web-based questionnaire, including the Pines Burnout Measure 2004-2006, were included. Registry data on sick leave spells from the response date until December 31, 2010 were obtained from the Swedish Social Insurance Agency. Logistic regression analysis was performed to assess odds ratios with 95% confidence intervals for the association between burnout and sick leave for the whole sample, while conditional logistic regression of the same-sex discordant twin pairs was used to estimate the association between burnout and sick leave, adjusting for familial confounding. The Bivariate Cholesky models were used to assess whether the covariation between burnout and sick leave was explained by common genetic and/or shared environmental factors.', 'Burnout was a risk factor for sick leave due to stress-related and other mental disorders, and these associations were explained by familial factors. The phenotypic correlation between burnout and sick leave due to somatic conditions was 0.07 and the association was not influenced by familial factors. The phenotypic correlations between burnout and sick leave due to stress-related (0.26) and other mental disorders (0.30) were completely explained by common genetic factors.",
            "output": [
                "Is the covariation between burnout and sick leave due to mental disorders explained by a shared genetic liability : a prospective swedish twin study with a five-year follow-up?"
            ]
        },
        {
            "id": "task847-fc3f3d71c7fc4f918397896094458a6d",
            "input": "It is recommended that dentists screen for dental anxiety (DA) so that fearful patients may be better managed. The main aim of this study was to determine what dentists are being taught in relation to DA as well as whether and how anxious patients are identified in the clinic.', 'Two hundred and forty-six practising dentists (adjusted response rate = 40.1%), from a random sample of registered Australian dentists, completed a mailed questionnaire.', \"Dentists estimated that high DA affected 23.3% of children and 19.4% of adults seen. Only 3.7% of dentists reported using a published scale for screening DA, with the most common reason being lack of awareness (56.5%). Approximately one-half of responding dentists directly asked their patients about DA and this was more common among younger dentists (\u03c7(2) = 7.75, p = 0.021). There were few differences in DA screening by other practitioner or practice characteristics (p > 0.05). Only one-third of dentists had received undergraduate training related to DA and only 41.7% considered this to be 'good' or better. Almost 37% of respondents expressed an interest in future training opportunities.",
            "output": [
                "Does dental anxiety screening practices and self-reported training need among Australian dentists?"
            ]
        },
        {
            "id": "task847-54f9d09a5f2448cb88f15d0b94639a05",
            "input": "Violence-exposed youth rarely receive mental health services, even though exposure increases risk for academic and psychosocial problems. This study examines the association between violence exposure and mental health service contact. The 4 forms of violence exposure were peer, family, sexual, and witnessing.', 'Data are from 1534 Boston public high school students who participated in a 2008 self-report survey of violence exposure and its correlates. Multivariate logistic regressions estimated associations between each form of violence with service contact, then examined whether associations persisted when controlling for suicidality and self-injurious behaviors.', 'In unadjusted models, violence-exposed students more often reported service contact than their peers. However, in multivariate models, only exposure to family (odds ratio [OR] = 1.69, 95% confidence interval [CI] = 1.23-2.31) and sexual violence (OR = 2.34, 95% CI = 1.29-4.20) were associated with service contact. Associations attenuated when controlling for suicidality and self-injurious behaviors, indicating they were largely explained by self-harm. Sexual violence alone remained associated with mental health service contact in fully adjusted models, but only for girls (OR=3.32, 95% CI=1.30-8.45), suggesting sex-specific pathways.",
            "output": [
                "Do mental health service use among high school students exposed to interpersonal violence?"
            ]
        },
        {
            "id": "task847-8edda7383864473d8122ed02c79d8914",
            "input": "The Musashi-2 gene (MSI2) is implicated in leukemogenesis, and high MSI2 expression has been associated with decreased survival in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), suggesting its use as a new prognostic marker. We aimed to validate the prognostic significance of MSI2 in ALL.', 'MSI2 expression was measured by real-time polymerase chain reaction in 140 adult B-ALL patients and compared to controls.', 'MSI2 expression level in patients was significantly higher when compared to the control group (P = 0.001). High MSI2 expression did not correlate with the clinical characteristics of patients. However, patients with high MSI2 expression had significantly lower incidence of complete remission (CR) (P = 0.03), inferior overall survival (P = 0.018), and shorter disease-free survival (P = 0.001). Multivariate analysis revealed that high MSI2 expression was an independent prognostic factor for adult BCR-ABL1-negative B-ALL patients.",
            "output": [
                "Does prognostic significance of MSI2 predict unfavorable outcome in adult B-acute lymphoblastic leukemia?"
            ]
        },
        {
            "id": "task847-98fe8def48634169b2a8e1bf2ab735a9",
            "input": "Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an autosomal recessive disease due to mutations in ABCB11. ABCB11 encodes the bile salt export pump (BSEP), the major transporter responsible for biliary bile acid secretion, which expression is restricted to hepatocytes. In some patients, molecular analysis of ABCB11 revealed either exonic or intronic variations - including common polymorphisms - predicted to affect splicing according to in silico analysis or in vitro minigene studies. Transcript analysis in liver tissue is the best way to determine whether the variations predicted to affect splicing are deleterious or not.', 'We performed ABCB11 transcript analysis in liver tissue from five PFIC2 patients who had variations which were predicted to either affect splicing or not. Among eleven variants tested, only the silent c.3003A>G variant and the intronic c.3213+4A>G variant led to abnormal splicing as suggested by in silico analysis.",
            "output": [
                "Does liver transcript analysis reveal aberrant splicing due to silent and intronic variations in the ABCB11 gene?"
            ]
        },
        {
            "id": "task847-e38612256aa14cbb84f04ca661320b4c",
            "input": "This single blind cross-sectional study compared the vascular health of subjects suffering from severe chronic periodontitis, severe aggressive periodontitis and periodontal healthy controls by evaluating pulse wave velocity (PWV), augmentation index (AIx) and pulse pressure amplification (PPA).', 'In a total of 158 subjects, 92 suffering from severe periodontitis and 66 matched periodontal healthy controls, PWV, AIx, central and peripheral blood pressure were recorded using an oscillometric device (Arteriograph).', 'Subjects suffering from severe chronic or aggressive periodontitis exhibited significantly higher PWV (p = 0.00004), higher AIx (p = 0.0049) and lower PPA (p = 0.028) than matched periodontal healthy controls.",
            "output": [
                "Are arterial stiffness and pulse wave reflection increased in patients suffering from severe periodontitis?"
            ]
        },
        {
            "id": "task847-5dc822511f6b414099588fdf62234964",
            "input": "Cisplatin-based chemotherapy is the standard of care for patients with muscle-invasive urothelial carcinoma. Pathologic downstaging to pT0/pTis after neoadjuvant cisplatin-based chemotherapy is associated with improved survival, although molecular determinants of cisplatin response are incompletely understood. We performed whole-exome sequencing on pretreatment tumor and germline DNA from 50 patients with muscle-invasive urothelial carcinoma who received neoadjuvant cisplatin-based chemotherapy followed by cystectomy (25 pT0/pTis \"responders,\" 25 pT2+ \"nonresponders\") to identify somatic mutations that occurred preferentially in responders. ERCC2, a nucleotide excision repair gene, was the only significantly mutated gene enriched in the cisplatin responders compared with nonresponders (q < 0.01). Expression of representative ERCC2 mutants in an ERCC2-deficient cell line failed to rescue cisplatin and UV sensitivity compared with wild-type ERCC2. The lack of normal ERCC2 function may contribute to cisplatin sensitivity in urothelial cancer, and somatic ERCC2 mutation status may inform cisplatin-containing regimen usage in muscle-invasive urothelial carcinoma.",
            "output": [
                "Do somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma?"
            ]
        },
        {
            "id": "task847-f59b27a68371419dbcdb03ad7e190553",
            "input": "Anemia is an established adverse risk factor in cardiovascular disease. However, the effect of preoperative anemia is not well defined in heart surgery. This study evaluates the effect of preoperative anemia on early clinical outcomes in patients undergoing cardiac surgery.', 'A retrospective, observational, cohort study of prospectively collected data was undertaken on 7,738 consecutive patients undergoing heart surgery between April 2003 and February 2009. Of these, 1,856 patients with preoperative anemia were compared to 5,882 patients without anemia (control group). According to the World Health Organization, anemia was defined as hemoglobin level\\u2009<\\u200913 g/dl for men and <12 g/dl for women. Selection bias not controlled by multivariable methods was assessed with propensity-adjustment method.', 'Overall mortality was 2.1%. Preoperative anemia was associated with tripling in the risk of death (4.6% vs 1.5%, p\\u2009<\\u20090.0001) and postoperative renal dysfunction (18.5% vs 6.5%, p\\u2009<\\u20090.0001). There was also a significant difference between the anemic and non-anemic group in the risk of postoperative stroke (1.9% vs 1.1%, p\\u2009=\\u20090.008), atrial fibrillation (36.7% vs 33%, p\\u2009=\\u20090.003) and length of hospital stay\\u2009>\\u20097 days (54% vs 36.7%, p\\u2009<\\u20090.0001). In propensity-adjusted, multivariable logistic regression, preoperative anemia was an independent predictor of mortality (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.02 to 2.03), postoperative renal dysfunction (OR 1.73, 95% CI 1.43 to 2.1) and length of hospital stay\\u2009>\\u20097 days (OR 1.3, 95% CI 1.15 to 1.47).",
            "output": [
                "Does preoperative anemia increase mortality and postoperative morbidity after cardiac surgery?"
            ]
        },
        {
            "id": "task847-ff692ef10a604a46ab878ab875f83cee",
            "input": "Angiogenesis and macrophage recruitment to the uterus are key features of uterine decidualization; the progesterone-mediated uterine changes that allow for embryo implantation and initiation of pregnancy. In the current study, we characterized the expression of vascular endothelial growth factor receptor-1 (VEGFR-1) in macrophages and endothelial cells of the peri-implantation uterus and determined if VEGFR-1 function is required for decidual angiogenesis, macrophage recruitment, and/or the establishment of pregnancy.', 'Expression of VEGFR-1 in uterine endothelial cells and macrophages was determined with immunohistochemistry. To assess the effect of continuous VEGFR-1 blockade, adult female mice were given VEGFR-1 blocking antibody, MF-1, every 3\\xa0days for 18\\xa0days. After 6 doses, females were mated and a final dose of MF-1 was given on embryonic day 3.5. Endothelial cells and macrophages were quantified on embryonic day 7.5. Pregnancy was analyzed on embryonic days 7.5 and 10.5.', 'F4/80(+) macrophages are observed throughout the stroma and are abundant adjacent to the endometrial lumen and glands prior to embryo implantation and scatter throughout the decidua post implantation. VEGFR-1 expression is restricted to the uterine endothelial cells. F4/80(+) macrophages were often found adjacent to VEGFR-1(+) endothelial cells in the primary decidual zone. Continuous VEGFR-1 blockade correlates with a significant reduction in decidual vascular and macrophage density, but does not affect embryo implantation or maintenance of pregnancy up to embryonic day 10.5.",
            "output": [
                "Does vEGFR-1 blockade disrupt peri-implantation decidual angiogenesis and macrophage recruitment?"
            ]
        },
        {
            "id": "task847-ac9b345e014d485b916fb7e91d558cfb",
            "input": "Despite VO\u2082peak being, generally, greater while running compared to cycling, ventilation (VE) during maximal exercise is less while running compared to cycling. Differences in operating lung volumes (OLV) between maximal running and cycling could be one explanation for previously observed differences in V E and this could be due to differences in body position e.g., trunk/hip angle during exercise.', 'We asked whether OLV differed between maximal running and cycling and if this difference was due to trunk/hip angle during exercise.', 'Eighteen men performed three graded maximal exercise tests; one while running, one while cycling in the drop position (i.e., extreme hip flexion), and one while cycling upright (i.e., seated with thorax upright). Resting flow-volume characteristics were measured in each body position to be used during exercise. Tidal flow-volume loops were measured throughout the exercise.', 'V E during maximal running (148.8 \u00b1 18.9 L min(-1)) tended to be lower than during cycling in the drop position (158.5 \u00b1 24.7 L min(-1); p = 0.07) and in the upright position (158.5 \u00b1 23.7 L min(-1); p = 0.06). End-inspiratory and end-expiratory lung volumes (EILV, EELV) were significantly larger during drop cycling compared to running (87.1 \u00b1 4.1 and 35.8 \u00b1 6.2 vs. 83.9 \u00b1 6.0 and 33.0 \u00b1 5.7% FVC), but only EILV was larger during upright cycling compared to running (88.2 \u00b1 3.5% FVC). OLV and V E did not differ between cycling positions.",
            "output": [
                "Are operating lung volumes affected by exercise mode but not trunk and hip angle during maximal exercise?"
            ]
        },
        {
            "id": "task847-472885579c604c26b26aa503f1d926e5",
            "input": "Identification of cancer or inflammatory bowel disease in the intestinal tract by PET/computed tomography (CT) imaging can be hampered by physiological uptake of F-fluorodeoxyglucose (F-FDG) in the normal colon. Previous work has localized this F-FDG uptake to the intestinal lumen, predominantly occupied by bacteria. We sought to determine whether pretreatment with an antibiotic could reduce F-FDG uptake in the healthy colon.', 'Thirty patients undergoing restaging PET/CT for nongastrointestinal lymphoma were randomly selected to receive rifaximin 550 mg twice daily for 2 days before their scan (post-rifaximin). Their PET/CT images were compared with those from their prior study (pre-rifaximin). Cecal maximum standard uptake value (SUVmax) and overall colonic F-FDG uptake were compared between scans. All PET/CT images were blindly scored by a radiologist. The same comparison of sequential scans was also undertaken in 30 patients who did not receive antibiotics.', \"Thirty post-rifaximin scans were compared with 30 pre-rifaximin scans in the same patients. SUVmax in the cecum was significantly lower in the patient's post-rifaximin scans than in their pre-rifaximin scans (P=0.002). The percentage of scans with greater than grade 1 colonic F-FDG uptake was significantly lower in the post-rifaximin scans than in the pre-rifaximin scans (P<0.05). In contrast, there was no significant difference in the paired sequential scans from control patients, nor a reduction in the percentage of scans with greater than grade 1 colonic F-FDG uptake.",
            "output": [
                "Does rifaximin suppress background intestinal 18F-FDG uptake on PET/CT scans?"
            ]
        },
        {
            "id": "task847-dfb17f9c84d5408d9213d7c38cd0858a",
            "input": "The aim of this study was the analysis of total, early and late complications following venous access port implantation between 1998 and 2008 at the Department of Surgery of the University of Rostock, Germany. A comparison between different implantation techniques addressing success rate, complication rate and duration of operation was performed. These results were further analysed in regard to the level of training of the participating surgeons.', 'A retrospective analysis of 1423 venous access port implantations between 1998 and 2008 was performed.', \"The rate of total complications was 13.8%. Among 4.7% early complications pneumothorax was the most common. The rate of late complications was 9.1%. Most common were infection (4.9%) followed by dysfunction of the catheter (3.5%). 1322 venous access port implantations were performed using puncture of the subclavian vein and Seldinger's technique. 101 operations were performed by direct access through dissection of the cephalic vein and open introduction of the catheter. Operation time in the open group was significantly longer than in the puncture group (46.5\\u2009min vs. 38.7\\u2009min, p\\u2009=\\u20090.005). There were significantly more late complications (9.6% vs. 2%, p\\u2009=\\u20090.01) and total complications (14.5% vs. 4%, p\\u2009=\\u20090.005) in the puncture group vs. the open access group. Primary success rates of open access vs. puncture were 100% and 96.8%, respectively. The rate of complications was independent of the experience status of the surgeon. However, the rate of total and late complications significantly decreases with number of performed operations.",
            "output": [
                "Is [ Venous Access Port Implantation an Ideal Teaching Operation - An Analysis of 1423 Cases ]?"
            ]
        },
        {
            "id": "task847-177042ec363549c68afa325d40959909",
            "input": "It has been hypothesized that minichromosome maintenance (MCM) proteins, which are replicative control factors, can be used to detect tumor proliferation. The aim of the present study was to investigate the expression of MCM in colorectal cancer tissues and correlate it to clinical outcomes.', 'The study included 145 patients with colorectal cancer who underwent curative surgery, from January 2002 until December 2004, at the Kurume University Hospital in Fukuoka, Japan. The median follow-up duration was 87 months. The expression of MCM7 in tissues was studied by immuno-histochemical staining. The labeling index (LI) of MCM7 was calculated by dividing the number of positively-stained cells by the total number of cells counted. We divided samples into two groups: positive (MCM7 LI 76% or higher) and negative (MCM7 LI less than 76%).', 'In patients with Dukes A and B, there were no significant differences in either overall survival (OS) or recurrence-free survival (RFS) between patents with MCM7-positive and those with MCM7-negative disease. On the other hand, in patients with Dukes C, there was significantly worse OS and RFS for patients with MCM7-positive compared to those with MCM7-negative disease.",
            "output": [
                "Is minichromosome maintenance protein 7 a risk factor for recurrence in patients with Dukes C colorectal cancer?"
            ]
        },
        {
            "id": "task847-50d8cf7019e240d6a6789589f21cd91f",
            "input": "Whether moderate to severe obesity (body mass index (BMI)\u226530 to <40kg/m(2)) contributes to breast cancer recurrence and mortality remains uncertain.', '1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and \u226540) were excluded from the analysis.', 'Of the 1155 included women, mean age, 58.4\u00b111.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR=1.71, 95%CI, 1.12-2.62, p=0.014), disease beyond Stage 1 (HR=2.87, 95% CI 1.73-4.75, p<0.001), OAET (HR=0.26, 95%CI 0.14-0.46, p<0.001), mastectomy (HR=3.28, 95%CI 1.98-5.44, p<0.001) and radiotherapy (HR=2.12, 95%CI 1.24-3.63, p=0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48-7.03, p=0.003) and OAET use (HR 0.41, 95%CI 0.17-0.98, p=0.046) were significantly associated with an event.",
            "output": [
                "Is obesity associated with a poorer prognosis in women with hormone receptor positive breast cancer?"
            ]
        },
        {
            "id": "task847-9ff3c102986646c9a02b8f5be7e9612d",
            "input": "Prostate cancer is one of the most common complex diseases with high leading cause of death in men. Identifications of prostate cancer associated genes and biomarkers are thus essential as they can gain insights into the mechanisms underlying disease progression and advancing for early diagnosis and developing effective therapies.', 'In this study, we presented an integrative analysis of gene expression profiling and protein interaction network at a systematic level to reveal candidate disease-associated genes and biomarkers for prostate cancer progression. At first, we reconstructed the human prostate cancer protein-protein interaction network (HPC-PPIN) and the network was then integrated with the prostate cancer gene expression data to identify modules related to different phases in prostate cancer. At last, the candidate module biomarkers were validated by its predictive ability of prostate cancer progression.', 'Different phases-specific modules were identified for prostate cancer. Among these modules, transcription Androgen Receptor (AR) nuclear signaling and Epidermal Growth Factor Receptor (EGFR) signalling pathway were shown to be the pathway targets for prostate cancer progression. The identified candidate disease-associated genes showed better predictive ability of prostate cancer progression than those of published biomarkers. In context of functional enrichment analysis, interestingly candidate disease-associated genes were enriched in the nucleus and different functions were encoded for potential transcription factors, for examples key players as AR, Myc, ESR1 and hidden player as Sp1 which was considered as a potential novel biomarker for prostate cancer.",
            "output": [
                "Does integrative analysis reveal disease-associated genes and biomarkers for prostate cancer progression?"
            ]
        },
        {
            "id": "task847-8b4e7cac95db4eaea92a07f227e2df0f",
            "input": "NI margins have to be chosen appropriately to control the risk of degradation of treatment effects in non-inferiority (NI) trials. We aimed to study whether the current choice of NI margins protects sufficiently against a degradation of treatment effect on an average.', 'NI trials reflecting current practice were assembled and for each trial, the NI margin was translated into a likelihood of degradation. The likelihood of degradation was calculated as the conditional probability of a treatment being harmful given that it is declared non-inferior in the trial, using simulation. Its distribution among the NI trials was then studied to assess the potential risk of degradation.', \"The median (lower/upper quartile) NI margin among 112 binary outcome NI trials corresponded to an odds ratio of 0.57(0.45, 0.66), while among 38 NI trials with continuous outcome, to a Cohen's d of -0.42(-0.54, -0.31) and a hazard ratio of 0.82(0.73, 0.86) among 24 survival outcome NI trials. Overall, the median likelihood of degradation was 56% (45%, 62%).",
            "output": [
                "Does choice of non-inferiority ( NI ) margins protect against degradation of treatment effects on an average -- an observational study of registered and published NI trials?"
            ]
        },
        {
            "id": "task847-6cc6fd8516e146b1919db76b34ccb527",
            "input": "The miss rate of colon polyps and its related factors have not been clearly identified yet. This study aims to review the miss rate of polyps both on the patient-level and on the polyp-level and to analyze the factors affecting the miss rate such as those related to the endoscopist, procedure, patient, and polyp.', 'From August 2011 to August 2013, patients who underwent elective second colonoscopy for resection of polyps, the sizes of which were not small enough to be resected by biopsy forceps alone at first colonoscopy, were enrolled retrospectively.', 'The miss rate on the patient-level was 59.2% (234/395) and on the polyp-level was 27.9% (578/2,068). There was no significant difference in the miss rate depending on the experience of the endoscopists or characteristics of the patients. In terms of the procedure, the miss rate was higher when the colonoscopy was performed in the afternoon (OR 1.632, p=0.046). It was found that the miss rate of polyps increased when the polyps were small (OR 4.595, p<0.001 in <5 mm/OR 3.447, p<0.001 in 5-10 mm), flat or sessile (OR 2.406, p<0.001 in flat/OR 1.768, p=0.002 in sessile), and located in the left colon (OR 1.391, p=0.007).",
            "output": [
                "Do [ Factors influencing the miss rate of polyps in a tandem colonoscopy study ]?"
            ]
        },
        {
            "id": "task847-34f96aace72143ed8870cfee32fb1d51",
            "input": "There are still many questions related to aseptic femoral stem loosening. Systemic and local immune responses to the implanted \"foreign body\" is one of the reasons for loosening. The purpose of the study was to measure metal ion concentration (Ti, Co, Cr, Mo, Ni, Al) around loosened femoral stems and compare their levels around uncemented and cemented implants.', 'This paper reports 50 hips operated for isolated stem loosening, in 50 patients at the mean age of 57 years (from 21 to 87). There were 25 cemented (Co,Cr29,Mo,Ni) and 25 uncemented (Ti, Al) stems. The mean follow-up from primary hip replacement to revision was 10.1 years (from 0.5 to 17). During the procedure, scar tissue around the stem was taken for analysis of metal ions.', 'The concentrations of titanium and aluminium in soft tissues around uncemented loosened stems were higher than cemented ones (p < 0.001, p < 0.001 respectively). However, no statistically significant differences were observed between both types of stems in terms of ions of the metal of which cemented implants had been made of (Co, Cr, Mo, Ni).",
            "output": [
                "Does metal debris concentrations in soft tissues adjacent to loosened femoral stem is higher in uncemented than cemented implants?"
            ]
        },
        {
            "id": "task847-cb1bb49dfe4c4405b5b47c36e0979bb9",
            "input": "Prognosis and treatment of patients with breast carcinoma of no special type (NST) is dependent on a few established parameters, such as tumor size, histological grade, lymph node stage, expression of estrogen receptor, progesterone receptor, and HER-2/neu, and proliferation index. The original Nottingham Prognostic Index (NPI) employs a three-tiered classification system that stratifies patients with breast cancer into good, moderate, and poor prognostic groups. The aim of our study was to use robust immunohistochemical methodology for determination of ER, PR, HER-2/neu, Ki-67, p53, and Bcl-2, and to observe differences in the expression of these markers when patients are stratified according to the original, three-tiered Nottingham Prognostic Index.', 'Paraffin blocks from 120 patients diagnosed with breast carcinoma, NST, were retrieved from our archive. Cases included in the study were female patients previously treated with modified radical mastectomy and axillary dissection.', 'Our study demonstrates that expression of markers of good prognosis, such as ER, PR, and Bcl-2, is seen with higher frequency in good and moderate NPI groups. In contrast, overexpression of HER-2/neu, a marker of adverse prognosis, is more frequent in moderate and poor NPI groups. High proliferation index, as measured by Ki-67, is seen in moderate and poor NPI groups, whereas low proliferation index is seen in good NPI groups.",
            "output": [
                "Does classification of patients with breast cancer according to Nottingham prognostic index highlight significant differences in immunohistochemical marker expression?"
            ]
        },
        {
            "id": "task847-cad28262277e45db8235735433930161",
            "input": "Mechanical support leads to an increased risk of both bleeding and thrombotic events, but little is known about the risk of device support in patients with a baseline predisposition to these events. The aim of this study was to examine outcomes among patients with baseline hematologic conditions who underwent continuous-flow LVAD implantation (CF-LVAD).', 'We retrospectively reviewed records of 286 patients who underwent CF-LVAD implantation at the Columbia University Medical Center between April 2008 and December 2013. Patients diagnosed with the following hematologic conditions were enrolled: idiopathic thrombocytopenic purpura (ITP); Factor V Leiden; elevated Factor VIII; heparin-induced thrombocytopenia (HIT); or undefined hypercoagulable state.', 'Of the 286 CF-LVAD patients implanted during the study period, 12 were considered to have a significant hematologic condition predisposing them to either bleeding or thrombotic events. The study included 5 patients with ITP, 1 with Factor V Leiden, 1 with elevated Factor VIII, 2 with HIT and 3 patients with undefined hypercoagulable state. Patients were supported for a total of 168.46 months, with a median of 10.76 months (IQR 4.78 to 21.36 months). There was a high frequency of thrombotic (0.57 event per patient-year), neurologic (0.36 event per patient-year) and bleeding (0.64 event per patient-year). Actuarial survival rates at 6 and 12 months were 81.8%, but fell to 49% at 2 years.",
            "output": [
                "Do prior hematologic conditions carry a high morbidity and mortality in patients supported with continuous-flow left ventricular assist devices?"
            ]
        },
        {
            "id": "task847-199c9eb93a7346279df24e8a412c3814",
            "input": "We recently demonstrated that MRI inflammation is prevalent in clinically non-swollen joints of early arthritis patients. In this study, we assessed the relevance of this subclinical inflammation with regard to radiographic progression.', '1130 joints (unilateral metacarpophalangeal 2-5, wrist and metatarsophalangeal 1-5) of 113 early arthritis patients underwent clinical examination and 1.5\\u2005T MRI at baseline, and radiographs at baseline and 1 year. Two readers scored the MRIs for synovitis, bone marrow oedema (BME) and tenosynovitis according to Rheumatoid Arthritis (RA) Magnetic Resonance Imaging (MRI) Scoring System (RAMRIS). Radiographic progression over 1 year was determined using the Sharp-van der Heijde scoring method.', 'On patient level, BME, synovitis and tenosynovitis were associated with radiographic progression, independent of known risk factors (p=0.003, 0.001 and 0.011, respectively). Of all non-swollen joints (n=932), 232 joints (26%) had subclinical inflammation (\u22651 MRI-inflammation feature present). These joints were distributed among 91% of patients. Radiographic progression was present in 4% of non-swollen joints with subclinical inflammation compared to 1% of non-swollen joints without subclinical inflammation (relative risks (RR) 3.5, 95% CI 1.3 to 9.6). Similar observations were done for BME (RR5.3, 95% CI 2.0 to 14.0), synovitis (RR3.4, 95% CI 1.2 to 9.3) and tenosynovitis (RR3.0, 95% CI 0.7 to 12.7) separately.",
            "output": [
                "Is mRI-detected subclinical joint inflammation associated with radiographic progression?"
            ]
        },
        {
            "id": "task847-e111fad3c44248e9b745a1974594d774",
            "input": "(1) Compare ideal cut-off points for DS and %FEV1 at 1 and 3\\xa0h\\xa0to predict hospitalization/relapse in subjects with moderate to severe asthma exacerbation (2) Develop a multivariate regression model using DS, %FEV1, demographic, and clinical variables to predict hospitalization/relapse.', 'Subjects with acute exacerbation of asthma (FEV1 <50% predicted following 30\\xa0min\\xa0of standardized treatment: 5\\xa0mg nebulized albuterol; 0.5-1.5\\xa0mg nebulized ipratropium; and 50\\xa0mg oral prednisone) were eligible. All subjects had %FEV1 and DS obtained at baseline and hourly for 3\\xa0h. Using hospitalization/relapse as the outcome of interest; we compared the area under the receiveroperator curves (AUC) between the 1 and 3\\xa0h\\xa0DS and %FEV1 measurements, and the AUC for the change in DS and %FEV1 between baseline and hour-3. We determined ideal cut-points for %FEV1 and DS to maximize sensitivity and specificity. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (LR) were compared between %FEV1 and DS. We developed a multivariate regression model examining the association of specific demographic and clinical variables to hospitalization/relapse.', '142 patients were included for analysis. The AUC was greatest for the 3-h\\xa0DS (0.721), followed by the 3-h\\xa0%FEV1 (0.669). Optimum cut-off values were a DS of 2, and an FEV1 of 42%. These were associated with a +LR for the composite outcome of 3.06 and 2.48 respectively. Logistic regression showed baseline DS, 3-h\\xa0DS, change in DS, and oxygen use at hour 3 were all associated with the composite outcome.",
            "output": [
                "Are repeated dyspnea score and percent FEV1 modest predictors of hospitalization/relapse in patients with acute asthma exacerbation?"
            ]
        },
        {
            "id": "task847-cf876520fba943bc86addcf33de38646",
            "input": "To evaluate whether the presence of mucinous differentiation influences histopathologic findings, stage distribution, or rate of recurrence among women with grade 1, endometrioid type, endometrial carcinoma.', 'This was a retrospective cohort study of all patients with grade 1, endometrioid type, endometrial carcinoma between January 2005 and December 2012. Patients were separated by the presence or absence of mucinous differentiation and then compared.', 'Of 655 patients, mucinous differentiation was present in 137 (20.9%) and absent in 518 (79.1%) patients. Compared to the group without mucinous differentiation, the group containing mucinous differentiation was older at diagnosis (mean: 61.1 vs. 58.5 years, OR, 95% CI; 1.03, 1.01-1.05) and more likely to have myometrial invasion (61.3% vs. 51.5%, OR, 95% CI; 1.49, 1.01-2.19). Additional histopathologic findings including: tumor size, cervical stromal invasion, adnexal involvement, LVI and/or the presence of positive lymph nodes were similar between groups. Mucinous differentiation did not affect stage distribution, as most patients were stage 1A (85.4% vs. 86.3%). The median PFS for the entire group has yet to be reached. The mean PFS for the entire study sample was 94.7 months. There was no difference in mean PFS when comparing the group with mucinous differentiation to the group without mucinous differentiation (98 vs. 93.4 months, p=0.07).",
            "output": [
                "Does mucinous differentiation impact stage or risk of recurrence among patients with grade 1 , endometrioid type , endometrial carcinoma?"
            ]
        },
        {
            "id": "task847-78c39ab7373e40c6a8dea029f7b93a0f",
            "input": "Lung cancer is the most important cause of cancer mortality worldwide, but the underlying mechanisms of this disease are not fully understood. Copy number variations (CNVs) are promising genetic variations to study because of their potential effects on cancer.', 'Here we conducted a pilot study in which we systematically analyzed the association of CNVs in two lung cancer datasets: the Environment And Genetics in Lung cancer Etiology (EAGLE) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial datasets. We used a preestablished association method to test the datasets separately and conducted a combined analysis to test the association accordance between the two datasets. Finally, we identified 167 risk SNP loci and 22 CNVs associated with lung cancer and linked them with recombination hotspots. Functional annotation and biological relevance analyses implied that some of our predicted risk loci were supported by other studies and might be potential candidate loci for lung cancer studies.",
            "output": [
                "Does combined analysis with copy number variation identify risk loci in lung cancer?"
            ]
        },
        {
            "id": "task847-2c92b7a9281e4b1e922a4392549ba573",
            "input": "Cumulative lifetime exposure to potentially traumatic events and serious life stressors has been linked with both mental and physical health problems; however, less is known about the association between exposure to potentially traumatic events and serious life stressors with health care use. We investigated whether a higher number of potentially traumatic events and serious life stressors were prospectively associated with an increased number of doctor visits and nights spent in the hospital.', 'Participants were drawn from the Health and Retirement Study, a prospective and nationally representative study of adults aged 50+ in the United States (n=7168). We analyzed the data using a generalized linear model with a gamma distribution and log link.', 'A higher number of potentially traumatic events and serious life stressors were associated with an increased number of doctor visits and nights spent in the hospital. On a 10-point scale, each additional potentially traumatic event or serious life stressor was associated with an 8% increase in doctor visits after controlling for sociodemographic factors (RR=1.08, 95% CI=1.06-1.11; p<.001). Each additional potentially traumatic event or serious life stressor was also associated with an 18% increase in the number of nights spent in the hospital after controlling for sociodemographic factors (RR=1.18, 95% CI=1.10-1.27; p<.001).",
            "output": [
                "Are potentially traumatic events and serious life stressors prospectively associated with frequency of doctor visits and overnight hospital visits?"
            ]
        },
        {
            "id": "task847-a072c5bbb1304833971e475c3153f079",
            "input": "DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation.', 'Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other.",
            "output": [
                "Does whole-genome bisulfite sequencing of multiple individuals reveal complementary roles of promoter and gene body methylation in transcriptional regulation?"
            ]
        },
        {
            "id": "task847-37996a71bb6f42df87b7858fff3cea7d",
            "input": "Upregulated CD64 expression on neutrophils is the most useful marker for acute bacterial infections and systemic inflammation. However, it is unknown whether CD64 is involved in the pathogenesis of acute pancreatitis (AP). This study was designed to determine whether CD64 is implicated in severe acute pancreatitis (SAP), and thus, is a suitable marker for SAP.', 'SAP was induced in rats with an intraperitoneal injection of L-arginine. CD64 expression in the rat pancreas was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Additionally, the CD64 mRNA expression in peripheral blood leukocytes from 21 patients with mild acute pancreatitis (MAP) and 10 patients with SAP was investigated at the time of admission and during remission by qRT-PCR.', 'CD64 mRNA and protein expression in the pancreas was significantly higher in rats with SAP, compared to the controls. The CD64 expression was higher in the patients with SAP than in the patients with MAP. During remission, CD64 mRNA decreased in both the MAP and SAP patients. The area under the curve of CD64 expression for the detection of SAP was superior to both the Ranson and the Acute Physiology and Chronic Health Evaluation II scores.",
            "output": [
                "Is cD64 expression increased in patients with severe acute pancreatitis : clinical significance?"
            ]
        },
        {
            "id": "task847-2d27625db14848f5891e9d088502b05f",
            "input": "Sepsis is a common disease that continues to increase in incidence in the world. Diseases, such as diabetes mellitus, may make the situation worse. Diabetic patients are at increased risk for common infections. This study was designed to investigate the role of glibenclamide on myocardial injury by lipopolysaccharides (LPS) in streptozotocin induced diabetic mice (STZ-mice).', 'LPS was used to induce endotoxemia in STZ-mice. Heart rate and mean arterial pressure were measured by MPA-HBBS. Serum epinephrine level was measured by enzyme-linked immunosorbent assays (ELISA). Myocardial injury was examined by light and transmission electron microscope and TUNEL staining. Macrophage infiltration was measured by immunohistochemistry. Interleukin-1\u03b2 (IL-1\u03b2) and tumor necrosis factor-\u03b1 (TNF-\u03b1) levels in myocardial tissue and serum in STZ-mice, and in conditional medium of primary cultured peritoneal macrophages were determined by ELISA. Nalp3 and Caspase-1 protein levels were measured by Western blotting analysis.', 'STZ administration decreased body weight and increased blood glucose in C57BL/6 mice. LPS injection caused decreases of heart rate and mean arterial pressure, and elevated serum epinephrine level in C57BL/6 mice. Compared with control mice without STZ treatment, LPS induced more severe myocardial injury and macrophage infiltration in STZ-mice, which was attenuated by pretreatment of glibenclamide. LPS stimulation enhanced the levels of IL-1\u03b2 and TNF-\u03b1 in both cardiac tissue and serum. Glibenclamide pretreatment significantly inhibited the serum levels of pro-inflammatory cytokines. Either high glucose or LPS increased the levels of IL-1\u03b2 and TNF-\u03b1 in the conditional medium of peritoneal macrophages. Glibenclamide treatment suppressed the increase of IL-1\u03b2 level induced by high glucose and LPS. Furthermore, Nalp3 and Caspase-1 levels were markedly increased by high glucose plus LPS, and both proteins were significantly inhibited by glibenclamide treatment.",
            "output": [
                "Does glibenclamide attenuate myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice?"
            ]
        },
        {
            "id": "task847-b8a5288628dc4527825db811526904b3",
            "input": "To investigate the associations between the mRNA levels of H19 in term placenta and risk of macrosomia.', 'Term placentas were collected from 37 macrosomia and 37 matched neonates with normal birth weight (controls) born in Changzhou Women and Children Health Hospital, Jiangsu province, P. R. China from March 1 to June 30, 2008. The mRNA levels of H19 in those placentas were measured by real-time polymerase chain reaction (PCR). Simple and multiple logistic regression models were used to explore the risk factors in the development of macrosomia. All analyses were performed using Stata 10.0 (StataCorp, College Station, Texas, USA).', \"The average H19 mRNA level of the macrosomia group was 1.450 \u00b10.456 while in the control group it was 2.080 \u00b11.296. Based on the result of Student's t test, there was a significant difference in H19 mRNA level between the macrosomia group and the control group (p = 0.008). After controlling for potential confounders, the multivariable adjusted odds ratio (OR) of macrosomia for those in the highest tertile of H19 mRNA level was 0.12 (95% CI: 0.02-0.59) when compared to those in the lowest tertile (p for linear trend = 0.009).",
            "output": [
                "Are maternal mRNA expression levels of H19 inversely associated with risk of macrosomia?"
            ]
        },
        {
            "id": "task847-d2b84a0dacec4a71a25f9e41aa3f5a0d",
            "input": "The mainstay of toxoplasmosis treatment targets the folate biosynthetic pathways and has not changed for the last 50 years. The activity of these chemotherapeutic agents is restricted to one lifecycle stage of Toxoplasma gondii, they have significant toxicity, and the impending threat of emerging resistance to these agents makes the discovery of new therapies a priority. We now demonstrate that auranofin, an orally administered gold containing compound that was FDA approved for treatment of rheumatoid arthritis, has activity against Toxoplasma gondii in vitro (IC50\\u200a=\\u200a0.28 \u00b5M) and in vivo (1 mg/kg).', 'Replication within human foreskin fibroblasts of RH tachyzoites was inhibited by auranofin. At 0.4 \u00b5M, auranofin inhibited replication, as measured by percent infected fibroblasts at 24 hrs, (10.94% vs. 24.66% of controls; p\\u200a=\\u200a0.0003) with no effect on parasite invasion (16.95% vs. 12.91% p\\u200a=\\u200a0.4331). After 18 hrs, 62% of extracellular parasites treated with auranofin were non-viable compared to control using an ATP viability assay (p\\u200a=\\u200a0.0003). In vivo, a previously standardized chicken embryo model of acute toxoplasmosis was used. Fourteen day old chicken embryos were injected through the chorioallantoic vein with 1\u00d7104 tachyzoites of the virulent RH strain. The treatment group received one dose of auranofin at the time of inoculation (1 mg/kg estimated body weight). On day 5, auranofin-treated chicken embryos were 100% protected against death (p\\u200a=\\u200a0.0002) and had a significantly reduced parasite load as determined by histopathology, immunohistochemistry and by the number of parasites quantified by real-time PCR.",
            "output": [
                "Is auranofin highly efficacious against Toxoplasma gondii in vitro and in an in vivo experimental model of acute toxoplasmosis?"
            ]
        },
        {
            "id": "task847-024b3390198d4f26bc7260881c1a570a",
            "input": "Cerebral deposition of phospho-tau in Alzheimer's disease (AD) occurs with varying patterns within hippocampus. Lamina-specific tau changes in AD may reflect trans-synaptic propagation of phospho-tau along neuroanatomical pathways.\", 'To study patterns of tau deposition within inner (IML) and outer (OML) molecular layers of dentate gyrus and their clinical and neuropathological correlates.', '98 consecutive autopsied brains from the Columbia University Brain Bank were stained for phospho-tau using AT-8. Staining density was rated as High versus Low within IML and OML. Four patterns were observed among the 98 brains: High IML&OML, n = 44; High OML Only (n = 35); High IML Only (n = 5); and Low IML&OML (n = 14). Demographic, clinical, and neuropathological characteristics of these four groups were compared.', 'High IML&OML subjects, versus High OML Only, were more likely to fulfill CERAD criteria for Definite AD (93% versus 66%, p < 0.01) and to have higher median Braak stage (6 versus 5, p < 0.01) and earlier mean age of onset (65.9 versus 73.7 y, p = 0.02), with similar symptom duration. Using logistic regression, the association between High IML&OML and AD remained significant after adjustment for demographics but not symptom duration. In the 70 subjects with Definite AD, High IML&OML was associated with younger age of onset (mean difference 3.7 years, 95%CI -6.7 to -0.7, p < 0.01), after adjustment for demographics and symptom duration.",
            "output": [
                "Does hippocampal laminar distribution of tau relate to Alzheimer 's disease and age of onset?"
            ]
        },
        {
            "id": "task847-4fc9a2a3fb004a05ac1faadebc773549",
            "input": "In contrast to middle cerebral artery territory strokes, anterior cerebral artery strokes (ACAS) occur rarely. The low frequency of ACAS, in relation to middle cerebral artery territory strokes, may be explained by differences in ACA and middle cerebral artery anatomy influencing their respective flow-directed embolism rates. We aimed to determine whether variability in ACA anatomy, and in particular A1 segment diameter, is associated with embolic ACAS.', 'Consecutive patients admitted to Boston Medical Center with embolic ACAS were reviewed. Ipsilateral and contralateral A1 diameters, M1 diameters, and terminal internal carotid artery bifurcation angles were measured from computed tomographic angiography and MRI angiography images. We compared these measurements between cases of ACAS and consecutive cases of embolic middle cerebral artery territory strokes.', 'The study comprised 55 individuals (27 ACAS, 28 middle cerebral artery territory strokes) with mean age of 69 years. In multivariate regression analysis, larger ipsilateral A1 diameters (odds ratio per 1 mm increment: 8.5; 95% confidence interval, 1.4-53.3) and ipsilateral A1/M1 diameter ratio (odds ratio per 10% increment: 1.8; 95% confidence interval, 1.2-2.9) were associated with ACAS, whereas larger ipsilateral M1 diameters was protective for ACAS (odds ratio per 1 mm increment: 0.8; 95% confidence interval, 0.0-0.9).",
            "output": [
                "Does larger A1/M1 diameter ratio predict embolic anterior cerebral artery territorial stroke?"
            ]
        },
        {
            "id": "task847-f26a3a8882d6406890931c214a8025e3",
            "input": "Intravenous immunoglobulin (IVIg) has been used to treat a variety of autoimmune disorders including multiple sclerosis (MS); however its mechanism of action remains elusive. Recent work has shown that interleukin-11 (IL-11) mRNAs are upregulated by IVIg in MS patient T cells. Both IVIg and IL-11 have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The objective of this study was to determine whether the protective effects of IVIg in EAE occur through an IL-11 and IL-11 receptor (IL-11R)-dependent mechanism.', 'We measured IL-11 in the circulation of mice and IL-11 mRNA expression in various organs after IVIg treatment. We then followed with EAE studies to test the efficacy of IVIg in wild-type (WT) mice and in mice deficient for the IL-11 receptor (IL-11R\u03b1-/-). Furthermore, we evaluated myelin-specific Th1 and Th17 responses and assessed spinal cord inflammation and demyelination in WT and IL-11R\u03b1-/- mice, with and without IVIg treatment. We also examined the direct effects of mouse recombinant IL-11 on the production of IL-17 by lymph node mononuclear cells.', 'IVIg treatment induced a dramatic surge (>1000-fold increase) in the levels of IL-11 in the circulation and a prominent increase of IL-11 mRNA expression in the liver. Furthermore, we found that IL-11R\u03b1-/- mice, unlike WT mice, although initially protected, were resistant to full protection by IVIg during EAE and developed disease with a similar incidence and severity as control-treated IL-11R\u03b1-/- mice, despite initially showing protection. We observed that Th17 cytokine production by myelin-reactive T cells in the draining lymph nodes was unaffected by IVIg in IL-11R\u03b1-/- mice, yet was downregulated in WT mice. Finally, IL-11 was shown to directly inhibit IL-17 production of lymph node cells in culture.",
            "output": [
                "Does optimal attenuation of experimental autoimmune encephalomyelitis by intravenous immunoglobulin require an intact interleukin-11 receptor?"
            ]
        },
        {
            "id": "task847-617e110911f5438dbe290dfe9e2d83af",
            "input": "Treatment of difficult asthma with oral corticosteroids (OCS) may suppress the hypothalamic-pituitary-adrenal axis.', 'In this study we have checked if the substitution of OCS with very high doses of ciclesonide may restore the adrenal function without losing the control of the disease.', 'In 5 patients with difficult, uncontrolled asthma despite treatment with OCS, inhaled and systemic glucocorticosteroids were replaced with very high doses of ciclesonide (1600-2400 \u00b5g/day). The symptoms of asthma and the lung function were assessed at baseline and on the 28(th), 56(th) and 70(th) day of treatment, whereas the levels of cortisol and adrenocorticotropic hormone (ACTH) in the morning were measured at baseline and on the 28(th) and the 56(th) day of treatment.', 'In all patients, the control of asthma symptoms, measured with Asthma Control Test questionnaire, improved from the mean score of 9.4 to 19.8 in 70 days. In 4 subjects force expiratory volume in 1 s improved gradually through the entire study reaching a mean improvement of 585 ml in 70 days. The ACTH levels were normalized in 3 patients after 28 days of observation and in all patients after 56 days. The cortisol level was normalized in 4 patients after 28 days and in another subject after 56 days of treatment with ciclesonide.",
            "output": [
                "Does switching from systemic steroids to ciclesonide restore the hypothalamic pituitary-adrenal axis?"
            ]
        },
        {
            "id": "task847-bfc63d9507b047dda5751df70eae171b",
            "input": "To assess levels of vitamin D and of immunoglobulin G subclasses in children and adolescents with type 1 Diabetes Mellitus with or without autoimmune thyroiditis.', 'Among 213 patients with type 1 diabetes, the cases with thyroid-specific autoantibodies formed Group 1 [n=19, M/F: 7/12, median age 13 years (10.1-14.7)]. Nineteen age-, gender-, and diabetes duration-matched cases with type 1 diabetes without any other systemic disease were designated as controls [Group 2, M/F: 7/12, median age 12.9 years (10.5-14.9)].', 'Levels of thyroid hormones, vitamin D, total IgG and IgG subclasses, as well as IgG subclasses/total IgG ratios were similar between the groups. Five cases (26%) in Group 1 had IgG4 levels > + 2 SDS, whereas there were no such cases in Group 2 (p=0.046). These five patients had similar clinical features but higher median IgG4 levels and IgG4/Total IgG ratios compared to the subjects with IgG4 levels < + 2 SDS in Group 1 and Group 2.",
            "output": [
                "Is autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus associated with elevated IgG4 but not with low vitamin D?"
            ]
        },
        {
            "id": "task847-ed4fe5bdf636420fb4718cbe3186798b",
            "input": "Recurrently mutated genes in myelodysplastic syndrome (MDS) are pathogenic drivers and powerfully associated with clinical phenotype and prognosis. Whether these types of mutations predict outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with MDS is not known.', 'We used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes.', 'Mutations were identified in 92% of patients, most frequently in the ASXL1 (29%), TP53 (21%), DNMT3A (18%), and RUNX1 (16%) genes. In univariable analyses, only TP53 mutations were associated with shorter overall (OS; hazard ratio [HR], 3.74; P < .001) and progression-free survival (HR, 3.97; P < .001). After adjustment for clinical variables associated with these end points, mutations in TP53 (HR, 2.30; P = .027), TET2 (HR, 2.40; P = .033), and DNMT3A (HR, 2.08; P = .049) were associated with decreased OS. In multivariable analysis including clinical variables, complex karyotype status, and candidate genes, mutations in TP53 (HR, 4.22; P \u2264 .001) and TET2 (HR, 1.68; P = .037) were each independently associated with shorter OS. Nearly one half of patients (46%) carried a mutation in TP53, DNMT3A, or TET2 and accounted for 64% of deaths. Three-year OS in patients without these mutations was 59% (95% CI, 43% to 72%), versus 19% (95% CI, 9% to 33%) in patients with these mutations.",
            "output": [
                "Do somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation?"
            ]
        },
        {
            "id": "task847-7005ad2889ae495ba8384d517ffa499d",
            "input": "It is suggested that maternal obesity perpetuates offspring obesity to future generations.', 'To determine whether location of neonate fat mass (FM: central vs. peripheral) is related to total neonate FM and whether maternal obesity influences this relationship.', 'Neonate body composition and skin-fold thicknesses were assessed in healthy neonates (n\\u2009=\\u2009371; 1-3 days old). Linear regression models examined the relationship between total FM and location of FM (central vs. peripheral). Location of FM was calculated by skin-folds: peripheral was the sum of (biceps and triceps)/2 and central was represented by the subscapular skin-fold.', 'A significant interaction was found for location of FM and maternal obesity. Holding all predictors constant, in offspring born to non-obese mothers, a 0.5\\u2009mm increase in central FM predicted a 15\\u2009g greater total FM, whereas a 0.5\\u2009mm increase in peripheral FM predicted a 66\\u2009g greater total FM. However, in offspring born to obese mothers, a 0.5\\u2009mm increase in central FM predicted a 56\\u2009g total FM, whereas a 0.5\\u2009mm increase in peripheral FM predicted a 14\\u2009g greater total FM.",
            "output": [
                "Does maternal obesity influence the relationship between location of neonate fat mass and total fat mass?"
            ]
        },
        {
            "id": "task847-6665a1c289c940b9885e9fee2ef1142c",
            "input": "The CXXC domain protein 4 (CXXC4) functions as a negative regulator of Wnt signaling and also regulates expression of the ten-eleven translocation 2 (TET2) protein for DNA methylation. This study detected levels of CXXC4 and TET2 mRNA to determine their association with survival of patients with myelodysplastic syndrome (MDS).', 'Levels of TET2 and CXXC4 mRNA were analyzed in bone marrow samples from 154 MDS patients and 50 control subjects using qRT-PCR and subsequently associated these levels with clinicopathological characteristics and survival of MDS patients.', 'Levels of TET2 and CXXC4 mRNA were significantly lower in MDS patients than that in controls (P=0.009 and P<0.001, respectively). Patients with advanced WHO subtypes (e.g., RAEB-1 and RAEB-2) exhibited a higher level of CXXC4 mRNA (P=0.020) compared to those with early stage subtypes (i.e., RA, RARS, RCMD, RCMD-RS, 5q-syndrome, and MDS-U). Moreover, levels of CXXC4 mRNA were associated with marrow blast levels (P=0.014) and neutrophil counts (P=0.039). Levels of CXXC4 mRNA and hemoglobin and IPSS cytopenias were associated with the overall survival (P=0.025) but not with the leukemia-free survival of MDS patients. The multivariate analysis demonstrated that the age of patients and levels of hemoglobin and marrow blast were independent risk factors for survival of MDS patients.",
            "output": [
                "Are cXXC4 mRNA levels associated with clinicopathological parameters and survival of myelodysplastic syndrome patients?"
            ]
        },
        {
            "id": "task847-63017a492e9b4721a05233c3c366b4e8",
            "input": "Is weight-training exercise intervention harmful to women with or at risk of breast cancer-related lymphoedema?', 'Systematic review with meta-analysis of randomised trials.', 'Women with or at risk of breast cancer-related lymphoedema.', 'Progressive weight-training exercise.', 'The primary outcomes were severity (volume difference) and incidence of arm lymphoedema. Secondary outcomes included muscle strength of the upper and lower limbs, quality of life and body mass index.', 'Eleven studies from eight trials involving 1091 women were included. Weight-training exercise of low to moderate intensity with relatively slow progression significantly improved the upper limb strength (SMD 0.93, 95% CI 0.73 to 1.12) and lower limb strength (SMD 0.75, 95% CI 0.47 to 1.04) without increasing the arm volume (SMD -0.09, 95% CI -0.23 to 0.05) or incidence of breast cancer-related lymphoedema (RR 0.77, 95% CI 0.52 to 1.15). No significant effects were noted for body mass index (SMD -0.10, 95% -0.31 to 0.11). Some aspects of quality of life may improve with weight training. PARTICIPANTS in all trials used pressure garments and received supervision; no trials used high-intensity weight training.",
            "output": [
                "Is weight training harmful for women with breast cancer-related lymphoedema : a systematic review?"
            ]
        },
        {
            "id": "task847-6e51193276bc4a849ae66ca6fd84a1a4",
            "input": "Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease and is a major cause of mortality in type 2 diabetes. Insulin sensitivity is an important determinant of renal health in adults with type 2 diabetes, but limited data exist in adolescents. We hypothesized that measured insulin sensitivity (glucose infusion rate [GIR]) would be associated with early markers of DN reflected by estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in adolescents with type 2 diabetes.', 'Type 2 diabetic (n = 46), obese (n = 29), and lean (n = 19) adolescents (15.1 \u00b1 2.2 years) had GIR measured by hyperinsulinemic-euglycemic clamps. ACR was measured and GFR was estimated by the Bouvet equation (combined creatinine and cystatin C).', 'Adolescents with type 2 diabetes had significantly lower GIR, and higher eGFR and ACR than obese or lean adolescents. Moreover, 34% of type 2 diabetic adolescents had albuminuria (ACR \u226530 mg/g), and 24% had hyperfiltration (\u2265135 mL/min/1.73 m2). Stratifying ACR and eGFR into tertiles, adolescents with type 2 diabetes in the highest tertiles of ACR and eGFR had respectively lower GIR than those in the mid and low tertiles, after adjusting for age, sex, Tanner stage, BMI, and HbA1c (P = 0.02 and P = 0.04). GIR, but not HbA1c, LDL, or systolic blood pressure, was also associated with eGFR after adjusting for sex and Tanner stage (\u03b2 \u00b1 SE: -2.23 \u00b1 0.87; P = 0.02).",
            "output": [
                "Is insulin sensitivity an important determinant of renal health in adolescents with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-1e9a71658dfb4864b83e4ac20420173a",
            "input": "To investigate the clinical significance of falling insulin requirements in women with preexisting or overt diabetes in pregnancy.', 'A retrospective review of 139 pregnancies was conducted in women, with preexisting diabetes, delivering between January 2010 and January 2013. Women with falling insulin requirements of 15% or more from the peak total daily dose in late pregnancy were considered case subjects (n = 35). The primary outcome consisted of a composite of clinical markers of placental dysfunction, including preeclampsia, small for gestational age (SGA, \u22645th percentile for gestational age), stillbirth (>20 weeks), and premature delivery (\u226430 weeks).', 'A total of 25.2% of women had >15% fall in insulin requirements with nulliparity as the only predictor at baseline (odds ratio [OR] 2.5 [95% CI 1.1-5.7], P = 0.03). Falling insulin requirements were associated with an increased risk of preeclampsia (OR 3.5 [1.1-10.7], P < 0.05) and the composite of clinical markers of placental dysfunction (4.4 [1.73-11.26], P = 0.002). Although falling insulin requirements were associated with higher rates of SGA (3.4 [1.0-11.3], P = 0.048), they were not associated with other adverse neonatal outcomes. However, there was a higher incidence of neonatal intensive care unit admission (15.5 [3.1-77.6], P = 0.001) and earlier delivery in this group (median 37.7 weeks [IQR 34.3-38.4] vs. 38.3 weeks [37.4-38.9], P = 0.014).",
            "output": [
                "Are falling insulin requirements associated with adverse obstetric outcomes in women with preexisting diabetes?"
            ]
        },
        {
            "id": "task847-ecd7035daecd46249165cb99a67c8253",
            "input": "microRNAs (miRNAs) are short RNAs that regulate gene expression in various processes, including immune response. Altered immune response is a pivotal event in the pathogenesis of celiac disease (CD), and miRNAs could have a role in modulating both innate and adaptive response to gluten in celiac patients.', 'We compared miRNA profiles in duodenal biopsies of controls and CD patients by miRNA array. Differentially expressed miRNAs were validated in controls, Marsh 3A-B, and Marsh 3C patients by quantitative PCR (qPCR). Target gene expression was assessed by qPCR, western blotting, and immunohistochemistry, and the effect of gliadin was evaluated by in vitro stimulation experiments on duodenal biopsies.', 'Seven miRNAs were identified as significantly downregulated in the duodenum of adult CD patients as compared with controls. qPCR validated the decreased expression of miR-192-5p, miR-31-5p, miR-338-3p, and miR-197, in particular in patients with more severe histological lesions (Marsh 3C). In silico analysis of possible miRNA targets identified several genes involved in innate and adaptive immunity. Among these, chemokine C-X-C motif ligand 2 (CXCL2) and NOD2 showed significantly increased mRNA and protein level in Marsh 3C patients and a significant inverse correlation with the regulatory miR-192-5p. In addition, forkhead box P3 (FOXP3), Run-related transcription factor 1, and interleukin-18 (targets of miR-31-5p, miR-338-3p, and miR-197, respectively) showed upregulation in CD patients. Furthermore, alterations in CXCL2 and NOD2, FOXP3, miR-192-5p, and miR-31-5p expression were triggered by gliadin exposure in CD patients.",
            "output": [
                "Do miRNAs affect the expression of innate and adaptive immunity proteins in celiac disease?"
            ]
        },
        {
            "id": "task847-a2f220c591134eab85c6c6ca65e619b2",
            "input": "The brain-derived neurotrophic factor (BDNF) gene is a candidate gene in therapeutic responses to antidepressants. The aim of the study was to determine the effects of BDNF allelic variability on responses to escitalopram treatment at 3\\xa0weeks after treatment initiation and at a 6-week endpoint.', 'We included 187 Caucasian subjects with depression; 153 completed the 6-week study. Clinical evaluation was performed using the Montgomery and Asberg Depression Rating Scale (MADRS) before and after 3-6 weeks of treatment.', 'After 3\\xa0weeks of treatment, we saw significantly better treatment responses in the Met carriers and greater antidepressant resistance among the Val/Val homozygotes. Relative to Val/Val homozygous (59.78\\xa0%), a significantly greater proportion of subjects Met-carriers (77.94\\xa0%) responded to escitalopram treatment (\u03c7 (2)\\u2009=\\u20095.88, p\\u2009=\\u20090.015). After 6\\xa0weeks, we found the same pattern of results but this effect did not reach statistical significance (\u03c7 (2)\\u2009=\\u20092.07, p\\u2009=\\u20090.15).",
            "output": [
                "Is the BDNF Val ( 66 ) Met polymorphism associated with escitalopram response in depressed patients?"
            ]
        },
        {
            "id": "task847-24c54b43918640838a715d2838a02d11",
            "input": "While motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing.\", 'Rhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating.', 'Parkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates.",
            "output": [
                "Does subthalamic deep brain stimulation improve auditory sensory gating deficit in Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-55171014fe5a4229a9598cdc2b1cabf8",
            "input": "Acute lung injury (ALI) is associated with high mortality due to the lack of effective therapeutic strategies. Mechanical ventilation itself can cause ventilator-induced lung injury. Pulmonary vascular barrier function, regulated in part by Src kinase-dependent phosphorylation of caveolin-1 and intercellular adhesion molecule-1 (ICAM-1), plays a crucial role in the development of protein-/neutrophil-rich pulmonary edema, the hallmark of ALI. Amide-linked local anesthetics, such as ropivacaine, have anti-inflammatory properties in experimental ALI. We hypothesized ropivacaine may attenuate inflammation in a \"double-hit\" model of ALI triggered by bacterial endotoxin plus hyperinflation via inhibition of Src-dependent signaling.', 'C57BL/6 (WT) and ICAM-1 (-/-) mice were exposed to either nebulized normal saline (NS) or lipopolysaccharide (LPS, 10\\xa0mg) for 1\\xa0hour. An intravenous bolus of 0.33\\xa0mg/kg ropivacaine or vehicle was followed by mechanical ventilation with normal (7\\xa0ml/kg, NTV) or high tidal volume (28\\xa0ml/kg, HTV) for 2\\xa0hours. Measures of ALI (excess lung water (ELW), extravascular plasma equivalents, permeability index, myeloperoxidase activity) were assessed and lungs were homogenized for Western blot analysis of phosphorylated and total Src, ICAM-1 and caveolin-1. Additional experiments evaluated effects of ropivacaine on LPS-induced phosphorylation/expression of Src, ICAM-1 and caveolin-1 in human lung microvascular endothelial cells (HLMVEC).', 'WT mice treated with LPS alone showed a 49% increase in ELW compared to control animals (p\\u2009=\\u20090.001), which was attenuated by ropivacaine (p\\u2009=\\u20090.001). HTV ventilation alone increased measures of ALI even more than LPS, an effect which was not altered by ropivacaine. LPS plus hyperinflation (\"double-hit\") increased all ALI parameters (ELW, EVPE, permeability index, MPO activity) by 3-4 fold compared to control, which were again decreased by ropivacaine. Western blot analyses of lung homogenates as well as HLMVEC treated in culture with LPS alone showed a reduction in Src activation/expression, as well as ICAM-1 expression and caveolin-1 phosphorylation. In ICAM-1 (-/-) mice, neither addition of LPS to HTV ventilation alone nor ropivacaine had an effect on the development of ALI.",
            "output": [
                "Does ropivacaine attenuate endotoxin plus hyperinflation-mediated acute lung injury via inhibition of early-onset Src-dependent signaling?"
            ]
        },
        {
            "id": "task847-2b8c98e91cc14c6895c0b1d0e451898b",
            "input": "Exosomes released from cells can transfer both functional proteins and RNAs between cells. In this study we tested the hypothesis that muscle cells might transmit specific signals during lipid-induced insulin resistance through the exosomal route.', 'Exosomes were collected from quadriceps muscles of C57Bl/6 mice fed for 16 weeks with either a standard chow diet (SD) or an SD enriched with 20% palm oil (HP) and from C2C12 cells exposed to 0.5 mmol/l palmitate (EXO-Post Palm), oleate (EXO-Post Oleate) or BSA (EXO-Post BSA).', 'HP-fed mice were obese and insulin resistant and had altered insulin-induced Akt phosphorylation in skeletal muscle (SkM). They also had reduced expression of Myod1 and Myog and increased levels of Ccnd1 mRNA, indicating that palm oil had a deep impact on SkM homeostasis in addition to insulin resistance. HP-fed mouse SkM secreted more exosomes than SD-fed mouse SkM. This was reproduced in-vitro using C2C12 cells pre-treated with palmitate, the most abundant saturated fatty acid of palm oil. Exosomes from HP-fed mice, EXO-Post Palm and EXO-Post Oleate induced myoblast proliferation and modified the expressions of genes involved in the cell cycle and muscle differentiation but did not alter insulin-induced Akt phosphorylation. Lipidomic analyses showed that exosomes from palmitate-treated cells were enriched in palmitate, indicating that exosomes likely transfer the deleterious effect of palm oil between muscle cells by transferring lipids. Muscle exosomes were incorporated into various tissues in vivo, including the pancreas and liver, suggesting that SkM could transfer specific signals through the exosomal route to key metabolic tissues.",
            "output": [
                "Do exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice?"
            ]
        },
        {
            "id": "task847-d44cbb24ecd04b2dac2c36a7e5db6770",
            "input": "B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms.', 'PMA induced THP-1-derived macrophages or human monocyte-derived macrophages were treated with recombinant IL-12 (rIL-12) or infected with adenovirus carrying human IL-12 gene (Ad-IL-12-GFP) for 24 h, then cocultured with the SKOV3 ovarian cancer cell line for another 24 h. Macrophages were collected for real-time PCR and Western blot to detect the expression of B7-H1, and activation of the NF-\u03baB signaling pathway. Moreover, supernatants were collected to assay for IL-12, IFN-\u03b3 and IL-10 by ELISA. In addition, monocyte-derived macrophages treated with IFN-\u03b3 were cocultured with SKOV3 and determined for the expression of B7-H1. Furthermore, the expression of B7-H1 in monocyte-derived macrophages was also evaluated after blocking NF-\u03baB signaling.', 'The expression of B7-H1 was significantly upregulated in monocyte-derived macrophages treated with rIL-12 or Ad-IL-12-GFP compared with the control groups (p<0.05), accompanied by a remarkable upregulation of IFN-\u03b3 (p<0.05), a marked downregulation of IL-10 (p<0.05) and activation of NF-\u03baB signaling. However, the upregulation of B7- H1 was inhibited by blocking the NF-\u03baB signaling pathway (p<0.05). Expression of B7-H1 was also increased (p<0.05) in monocyte-derived macrophages treated with IFN-\u03b3 and cocultured with SKOV3. By contrast, the expression of B7-H1 in THP-1-derived macrophages was significantly decreased when treated in the same way as monocyte-derived macrophages (p<0.05), and IL-10 was also significantly decreased but IFN-\u03b3 was almost absent.",
            "output": [
                "Does iL-12 regulate B7-H1 expression in ovarian cancer-associated macrophages by effects on NF-\u03baB signalling?"
            ]
        },
        {
            "id": "task847-641345b0050e417ea1e77e826475d076",
            "input": "Vitamin A plays a major role in lipid metabolism. Previously, we reported that chronic vitamin A feeding (129 mg/kg) for two months normalized the abnormally high plasma HDL-cholesterol (HDL-C) levels in hypercholesterolemic obese rats by upregulating the hepatic scavenger receptor class B type 1 (SR-BI) expression. In this report, we hypothesize that the administration of a dose less than 129 mg of vitamin A/kg would also be effective in lowering the plasma HDL-C levels in these rats.', 'Changes in the activity and expression of proteins related to RCT were analyzed together with blood parameters in five-month-old male lean and obese rats supplemented with 2.6 (control group), 26, 52 and 129 mg of vitamin A/kg as retinyl palmitate for 20 weeks.', 'Vitamin A supplementation in the obese rats decreased the plasma HDL-C levels with a concomitant increase in the hepatic SR-BI expression and lipase activity compared to that observed in the control diet-fed obese rats treated with 2.6 mg of vitamin A/kg diet. Furthermore, vitamin A supplementation at doses of 52 and 129 mg/kg diet reduced the plasma lecithin cholesterol acyltransferase activity and increased the hepatic ATP-binding cassette transporter protein A1 expression in the obese rats. Interestingly, most of these changes were not observed in the lean rats fed a vitamin A-enriched diet.",
            "output": [
                "Does vitamin A-enriched diet modulate reverse cholesterol transport in hypercholesterolemic obese rats of the WNIN/Ob strain?"
            ]
        },
        {
            "id": "task847-f7df3b31adcd4c7ca28209c2458f9a2f",
            "input": "Video-EEG monitoring in the epilepsy monitoring unit (EMU) is a limited clinical resource. Knowledge of the predicting factors for length of stay (LOS) in the EMU may allow providers to more efficiently utilize EMU bed space.', 'The records for all consecutive admissions to the EMU at the University of Colorado Hospital between December 1, 2010 and May 31, 2011 (n = 142) were retrospectively reviewed.', 'Univariate analyses focusing on variables known prior to admission showed that EMU LOS (in hours) was not significantly correlated with patient age, number of event types, or number of antiepileptic drugs at admission. Patients who were admitted to the EMU for event characterization had statistically significantly shorter average LOS than patients who had been admitted as a part of a presurgical evaluation. Patients who reported < = 1 seizure per week had a statistically significantly higher average LOS than patients who reported >= 1 seizure per day. These variables were also significantly predictive of total LOS (p < 0.0001 and p = 0.03, respectively) in multivariate analysis.",
            "output": [
                "Do pre-admission clinical factors affect length of stay in the epilepsy monitoring unit?"
            ]
        },
        {
            "id": "task847-2e29c159a21f42dfb7547e9fcb665558",
            "input": "Current views on the control of cell development are anchored on the notion that phenotypes are defined by networks of transcriptional activity. The large amounts of information brought about by transcriptomics should allow the definition of these networks through the analysis of cell-specific transcriptional signatures. Here we test this principle by applying an analogue to comparative anatomy at the cellular level, searching for conserved transcriptional signatures, or conserved small gene-regulatory networks (GRNs) on root hairs (RH) and pollen tubes (PT), two filamentous apical growing cells that are a striking example of conservation of structure and function in plants.', 'We developed a new method for isolation of growing and mature root hair cells, analysed their transcriptome by microarray analysis, and further compared it with pollen and other single cell transcriptomics data. Principal component analysis shows a statistical relation between the datasets of RHs and PTs which is suggestive of a common transcriptional profile pattern for the apical growing cells in a plant, with overlapping profiles and clear similarities at the level of small GTPases, vesicle-mediated transport and various specific metabolic responses. Furthermore, cis-regulatory element analysis of co-regulated genes between RHs and PTs revealed conserved binding sequences that are likely required for the expression of genes comprising the apical signature. This included a significant occurrence of motifs associated to a defined transcriptional response upon anaerobiosis.",
            "output": [
                "Does transcriptional profiling of Arabidopsis root hairs and pollen define an apical cell growth signature?"
            ]
        },
        {
            "id": "task847-5f81dbebaa1a4819a36a26e9e0e5af75",
            "input": "Despite their high prevalence, sleep disorders often remain unrecognized and untreated because of barriers to assessment and management. The aims of the present study were to examine associations of complaints of sleep disturbances with cardiovascular disease, related risk factors, and inflammation in the community and to determine the contribution of sleep disturbances to self-perceived physical health.', 'The sample consists of n\\u200a=\\u200a10.000 participants, aged 35 to 74 years of a population based community sample in Germany. Cross-sectional associations of complaints of sleep disturbances with cardiovascular risk factors and disease, biomarkers of inflammation, depression, anxiety, and physical health status were analyzed.', '19% of our sample endorsed clinically significant sleep disturbances. In the unadjusted analyses severity of sleep disturbances increased with female sex, low socioeconomic status, living without a partnership, cardiovascular disease, depression, anxiety, poor physical health, increased levels of C-reactive protein and fibrinogen. After multivariate adjustment robust associations with coronary heart disease, myocardial infarction and dyslipidemia remained. Complaints of sleep disturbances were strong and independent contributors to self-perceived poor physical health beyond depression, anxiety and medical disease burden.",
            "output": [
                "Are complaints of sleep disturbances associated with cardiovascular disease : results from the Gutenberg Health Study?"
            ]
        },
        {
            "id": "task847-9c068f5a43ee48e78515677b0cb6a56a",
            "input": "Conflicting results have been reported regarding the predicative roles of alloreactive natural killer (NK) cells on the outcomes of transplantation in leukaemia patients.', 'We prospectively analysed the human leukocyte antigen (HLA) typing of donor-recipient pairs and the KIR typing of the donors in 97 CML patients to address the predictive roles of NK cells in relapse undergoing T-cell-replete haploidentical transplantation.', \"Patients with class I ligands for the donor-inhibitory KIR gene exhibited decreased molecular and haematologic relapse rates (P=0.003 and P=0.015, respectively). There was a significantly reduced risk of molecular and haematologic relapse in patients with HLA-C1C2 or C2C2 who accepted donors with KIR2DS1 or in patients with HLA-Bw4 who accepted donors with KIR3DS1 ('recipient with relevant KIR ligand for donor-activating KIR', n=25), compared with the remaining transplants (n=72, P=0.009 and P=0.009, respectively). In addition, the presence of class I ligand in the recipients of donor-activating KIR contributed to a decreased relapse rate in patients lacking class I ligand in the recipient of donor-inhibitory KIR (P=0.04 and P=0.03, respectively).",
            "output": [
                "Does hLA and KIR genotyping correlate with relapse after T-cell-replete haploidentical transplantation in chronic myeloid leukaemia patients?"
            ]
        },
        {
            "id": "task847-ddd93f51ed3a45dc8ba9c9aa884bc74a",
            "input": "Cetuximab is often combined with radiotherapy in advanced SCCHN. Alternative routes bypassing inhibition of EGFR with cetuximab may overshadow the efficacy of this combination. We undertook this study to investigate a possible role of dasatinib in this scenario.', 'The SCC5, SCC25, SCC29, FaDu and A431 cell lines were assessed in vitro for cell proliferation under cetuximab and dasatinib treatments. In FaDu and A431 cells, dasatinib plus cetuximab resulted in higher proliferation than cetuximab alone. Then, FaDu and A431 cells were implanted into subcutaneous tissue of athymic mice that were irradiated with 30\\u2009Gy in 10 fractions over 2 weeks, and treated with cetuximab and dasatinib. Tumour growth, DNA synthesis and angiogenesis were determined. The EGFR, RAS-GTP activity, phosphorylated AKT, ERK1/2, SRC protein levels and VEGF secretion were determined in vitro.', 'The addition of dasatinib to cetuximab and radiotherapy increased tumour growth, DNA synthesis and angiogenesis that were associated with RAS, AKT and ERK1/2 activation, and SRC inhibition in FaDu and A431 cells.",
            "output": [
                "Does dasatinib worsen the effect of cetuximab in combination with fractionated radiotherapy in FaDu- and A431-derived xenografted tumours?"
            ]
        },
        {
            "id": "task847-6ba6635fd3cb42bcbe886fb19e6326fd",
            "input": "To assess the predictive value of glycated albumin (GA) and other risk factors on a progression of diabetic retinopathy (DR).', 'In this retrospective longitudinal study, we enrolled the subjects with type 2 diabetes who had undergone fundus photography twice with a 5-years gap between January 2006 and December 2012, and had been measured consecutively for hemoglobin A1c (HbA1c) and GA levels every 3 or 6 months. The subjects were divided into two groups with or without a progression of DR. The mean HbA1c and mean GA were calculated separately by the sum of all measured values divided by the numbers of values throughout the study period.', 'Of the 359 subjects, progression group showed significantly higher diabetes duration (8.41\u00b15.72 vs. 6.46\u00b15.77, P<0.01), baseline HbA1c (9.13\u00b12.71 vs. 8.41\u00b12.32, P<0.05), fasting plasma glucose (8.71\u00b12.78 vs. 7.94\u00b12.63, P<0.05), 2h-postprandial glucose (15.12\u00b111.20 vs.13.14\u00b14.72, P<0.05), eGFR (114.81\u00b139.15 vs. 103.23\u00b132.18, P<0.01), mean HbA1c (8.32\u00b11.69 vs. 7.39\u00b11.35, P<0.01) and mean GA (22.66\u00b15.92 vs. 19.83\u00b15.18, P<0.01) than non-progression group. The frequencies of subjects with DR progression increased obviously with the increment of baseline HbA1c, mean HbA1c and mean GA according to quartile stratification of the above three glucose parameters. Multivariable binary logistic regression analysis investigated that the factors affected the DR progression were the presence of DR at baseline (OR=0.391, P=0.005), mean HbA1c (OR=1.389, P=0.021), mean GA (OR=1.087, P=0.039) and eGFR (OR=1.008, P=0.045). The optimal cut-off values of mean HbA1c and GA to predict DR progression were 7.27% and 21.85%, respectively.",
            "output": [
                "Does serum glycated albumin predict the progression of diabetic retinopathy -- a five year retrospective longitudinal study?"
            ]
        },
        {
            "id": "task847-daed5cccc71646928e82123909bb3423",
            "input": "This study was designed to measure the impact of bacterial biofilms on diffusion of an ocular therapeutic through silicone hydrogel bandage lenses in vitro.', 'An assay was designed to study the passage of a commonly used steroid, dexamethasone, through silicone hydrogel soft contact lenses. Diffused dexamethasone was measured using a spectrophotometer over a period of 18 hours and quantified using a standard curve. This assay was performed with control and Staphylococcus epidermidis biofilm-coated contact lenses comprised of lotrafilcon A and methafilcon. Biofilms were formed in brain heart infusion broth supplemented with D-glucose.', 'The presented data validate a simple in vitro model that can be used to measure the penetration of a topical therapeutic through silicone hydrogel soft contact lenses. Using this model, we measured a reduction in dexamethasone diffusion up to 88% through S. epidermidis biofilm-coated silicone hydrogel lenses compared with control lenses.",
            "output": [
                "Is dexamethasone diffusion across contact lenses inhibited by Staphylococcus epidermidis biofilms in vitro?"
            ]
        },
        {
            "id": "task847-1cafbe98f60543e8b787f23f02b644fa",
            "input": "Overexpression of ribosomal RNA processing 1 homolog B (RRP1B) induces a transcriptional profile that accurately predicts patient outcome in breast cancer. However, the mechanism by which RRP1B modulates transcription is unclear. Here, the chromatin-binding properties of RRP1B were examined to define how it regulates metastasis-associated transcription. To identify genome-wide RRP1B-binding sites, high-throughput ChIP-seq was performed in the human breast cancer cell line MDA-MB-231 and HeLa cells using antibodies against endogenous RRP1B. Global changes in repressive marks such as histone H3 lysine 9 trimethylation (H3K9me3) were also examined by ChIP-seq. Analysis of these samples identified 339 binding regions in MDA-MB-231 cells and 689 RRP1B-binding regions in HeLa cells. Among these, 136 regions were common to both cell lines. Gene expression analyses of these RRP1B-binding regions revealed that transcriptional repression is the primary result of RRP1B binding to chromatin. ChIP-reChIP assays demonstrated that RRP1B co-occupies loci with decreased gene expression with the heterochromatin-associated proteins, tripartite motif-containing protein 28 (TRIM28/KAP1), and heterochromatin protein 1-\u03b1 (CBX5/HP1\u03b1). RRP1B occupancy at these loci was also associated with higher H3K9me3 levels, indicative of heterochromatinization mediated by the TRIM28/HP1\u03b1 complex. In addition, RRP1B upregulation, which is associated with metastasis suppression, induced global changes in histone methylation.",
            "output": [
                "Does metastasis-associated protein ribosomal RNA processing 1 homolog B ( RRP1B ) modulate metastasis through regulation of histone methylation?"
            ]
        },
        {
            "id": "task847-8c0744d6c7d543c9a1c0ee75430d502b",
            "input": "DNA barcodes are short unique sequences used to label DNA or RNA-derived samples in multiplexed deep sequencing experiments. During the demultiplexing step, barcodes must be detected and their position identified. In some cases (e.g., with PacBio SMRT), the position of the barcode and DNA context is not well defined. Many reads start inside the genomic insert so that adjacent primers might be missed. The matter is further complicated by coincidental similarities between barcode sequences and reference DNA. Therefore, a robust strategy is required in order to detect barcoded reads and avoid a large number of false positives or negatives.For mass inference problems such as this one, false discovery rate (FDR) methods are powerful and balanced solutions. Since existing FDR methods cannot be applied to this particular problem, we present an adapted FDR method that is suitable for the detection of barcoded reads as well as suggest possible improvements.', 'In our analysis, barcode sequences showed high rates of coincidental similarities with the Mus musculus reference DNA. This problem became more acute when the length of the barcode sequence decreased and the number of barcodes in the set increased. The method presented in this paper controls the tail area-based false discovery rate to distinguish between barcoded and unbarcoded reads. This method helps to establish the highest acceptable minimal distance between reads and barcode sequences. In a proof of concept experiment we correctly detected barcodes in 83% of the reads with a precision of 89%. Sensitivity improved to 99% at 99% precision when the adjacent primer sequence was incorporated in the analysis. The analysis was further improved using a paired end strategy. Following an analysis of the data for sequence variants induced in the Atp1a1 gene of C57BL/6 murine melanocytes by ultraviolet light and conferring resistance to ouabain, we found no evidence of cross-contamination of DNA material between samples.",
            "output": [
                "Does enhancing the detection of barcoded read in high throughput DNA sequencing data by controlling the false discovery rate?"
            ]
        },
        {
            "id": "task847-084c7ba4552f4fc3a7dfe4d18324524b",
            "input": "The molecular mechanisms of the vasoconstrictor responses evoked by hydrogen peroxide (H2O2) have not been clearly elucidated in skeletal muscle arterioles.', 'Changes in diameter of isolated, cannulated and pressurized gracilis muscle arterioles (GAs) of Wistar-Kyoto rats were determined under various test conditions. H2O2 (10-100 \u00b5M) evoked concentration-dependent constrictions in the GAs, which were inhibited by endothelium removal, or by antagonists of phospholipase A (PLA; 100 \u00b5M 7,7-dimethyl-(5Z,8Z)-eicosadienoic acid), protein kinase C (PKC; 10 \u00b5M chelerythrine), phospholipase C (PLC; 10 \u00b5M U-73122), or Src family tyrosine kinase (Src kinase; 1 \u00b5M Src Inhibitor-1). Antagonists of thromboxane A2 (TXA2; 1 \u00b5M SQ-29548) or the non-specific cyclooxygenase (COX) inhibitor indomethacin (10 \u00b5M) converted constrictions to dilations. The COX-1 inhibitor (SC-560, 1 \u00b5M) demonstrated a greater reduction in constriction and conversion to dilation than that of COX-2 (celecoxib, 3 \u00b5M). H2O2 did not elicit significant changes in arteriolar Ca(2+) levels measured with Fura-2.",
            "output": [
                "Does hydrogen peroxide elicit constriction of skeletal muscle arterioles by activating the arachidonic acid pathway?"
            ]
        },
        {
            "id": "task847-bc94b1f02d884a0bb7e414a869d5d346",
            "input": "Cigarette smoking is a major risk factor for atherosclerotic cardiovascular disease, which is responsible for a significant proportion of smoking-related deaths. However, the precise mechanism whereby smoking induces this pathology has not been fully delineated. Based on observation of DNA double-strand breaks (DSBs), the most harmful type of DNA damage, in atherosclerotic lesions, we hypothesized that there is a direct association between smoking and DSBs. The goal of this study was to investigate whether smoking induces DSBs and smoking cessation reverses DSBs in vivo through examination of peripheral mononuclear cells (MNCs).', 'Immunoreactivity of oxidative modification of DNA and DSBs were increased in human atherosclerotic lesions but not in the adjacent normal area. DSBs in human MNCs isolated from the blood of volunteers can be detected as cytologically visible \"foci\" using an antibody against the phosphorylated form of the histone H2AX (\u03b3-H2AX). Young healthy active smokers (n = 15) showed increased \u03b3-H2AX foci number when compared with non-smokers (n = 12) (foci number/cell: median, 0.37/cell; interquartile range [IQR], 0.31-0.58 vs. 4.36/cell; IQR, 3.09-7.39, p<0.0001). Smoking cessation for 1 month reduced the \u03b3-H2AX foci number (median, 4.44/cell; IQR, 4.36-5.24 to 0.28/cell; IQR, 0.12-0.53, p<0.05). A positive correlation was noted between \u03b3-H2AX foci number and exhaled carbon monoxide levels (r = 0.75, p<0.01).",
            "output": [
                "Does smoking cessation reverse DNA double-strand breaks in human mononuclear cells?"
            ]
        },
        {
            "id": "task847-acd5310354244cf2a26b99e24839069d",
            "input": "Aging and chronic alcohol consumption are both modifiers of DNA methylation, but it is not yet known whether chronic alcohol consumption also alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by oxidation of methylcytosine. Furthermore, it has not been tested whether aging and alcohol interact to modify this epigenetic phenomenon, thereby having an independent effect on gene expression.', 'Old (18\\xa0months) and young (4\\xa0months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18% of energy) or an isocaloric Lieber-DeCarli control diet for 5\\xa0weeks. Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA using a new liquid chromatography-tandem mass spectrometry method. Hepatic mRNA expression of the Tet enzymes were measured via quantitative real-time polymerase chain reaction.', 'In young mice, mild chronic alcohol exposure significantly reduced global DNA hydroxymethylation compared with control mice (0.22\\xa0\u00b1\\xa00.01 vs. 0.29\\xa0\u00b1\\xa00.06%, p\\xa0=\\xa00.004). Alcohol did not significantly alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet showed decreased global DNA hydroxymethylation compared with young mice fed the control diet (0.24\\xa0\u00b1\\xa00.02 vs. 0.29\\xa0\u00b1\\xa00.06%, p\\xa0=\\xa00.04). This model suggests an interaction between aging and alcohol in determining DNA hydroxymethylation (pinteraction \\xa0=\\xa00.009). Expression of Tet2 and Tet3 was decreased in the old mice relative to the young (p\\xa0<\\xa00.005).",
            "output": [
                "Do aging and alcohol interact to alter hepatic DNA hydroxymethylation?"
            ]
        },
        {
            "id": "task847-7026ed0b811a44878a48bf1e5cf8f7a2",
            "input": "To evaluate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and the presence of a Chronic Venous Disorder (CVD).', \"We included 55 subjects with CCSVI aged >18 years, and 186 controls without CCSVI. Each subject was evaluated with color Doppler sonography in accordance with Zamboni's five criteria, examined by two neurologists and interviewed with an ad-hoc designed form. The neurologists and the sonographers were mutually blinded. CVD were classified according to CEAP.\", 'Mean age was 42 years (SD\\u2009=\\u20099) in cases and 43 years (10) in controls (p\\u2009=\\u2009ns). The odds ratios in subjects CCSVI were 0.6 (0.2-2.2) for CEAP 1, 0.9 (0.2-4.5) for CEAP 2, and 1.0 (0.6-1.9) for family history of varicose veins. The prevalence of CVD and, family history of varicose veins, was similar between cases and controls for each Zamboni criterion.",
            "output": [
                "Is chronic cerebrospinal venous insufficiency associated with chronic venous disorders : A case-control study?"
            ]
        },
        {
            "id": "task847-100d278c3be34192b8c2ff79870399b9",
            "input": "Granulation tissue remodeling and myofibroblastic differentiation are critically important events during wound healing. Tobacco smoking has a detrimental effect in gingival tissue repair. However, studies evaluating the effects of cigarette smoke on these events are lacking.', 'We used gingival fibroblasts cultured within free-floating and restrained collagen gels to simulate the initial and final steps of the granulation tissue phase during tissue repair. Collagen gel contraction was stimulated with serum or transforming growth factor-\u03b21. Cigarette smoke condensate (CSC) was used to evaluate the effects of tobacco smoke on gel contraction. Protein levels of alpha-smooth muscle actin, \u03b21 integrin, matrix metalloproteinase-3 and connective tissue growth factor were evaluated through Western blot. Prostaglandin E(2) (PGE(2)) levels were determined through ELISA. Actin organization was evaluated through confocal microscopy.', 'CSC reduced collagen gel contraction induced by serum and transforming growth factor-\u03b21 in restrained collagen gels. CSC also altered the development of actin stress fibers in fibroblasts cultured within restrained collagen gels. PGE(2) levels were strongly diminished by CSC in three-dimensional cell cultures. However, other proteins involved in granulation tissue remodeling and myofibroblastic differentiation such as alpha-smooth muscle actin, \u03b21 integrin, matrix metalloproteinase-3 and connective tissue growth factor, were unmodified by CSC.",
            "output": [
                "Does cigarette smoke condensate inhibit collagen gel contraction and prostaglandin E2 production in human gingival fibroblasts?"
            ]
        },
        {
            "id": "task847-e02d17b84aec40218d8740d4b462db92",
            "input": "Infants suffering from neonatal sepsis face an increased risk of early death and long-term neurodevelopmental delay. This paper analyses and summarises the existing data on short-term and long-term outcomes of neonatal sepsis, based on 12 studies published between January 2000 and 1 April 2012 and covering 3669 neonates with sepsis.",
            "output": [
                "Does meta-analysis show that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications?"
            ]
        },
        {
            "id": "task847-640340914e714d98b9a381a770527eef",
            "input": "To test the role of mast cells in gut inflammation and colitis using interleukin (IL)-10-deficient mice as an experimental model.', 'Mast cell-deficient (Kit (W-sh/W-sh) ) mice were crossbred with IL-10-deficient mice to obtain double knockout (DKO) mice. The growth, mucosal damage and colitis status of DKO mice were compared with their IL-10-deficient littermates.', 'DKO mice exhibited exacerbated colitis compared with their IL-10-deficient littermates, as shown by increased pathological score, higher myeloperoxidase content, enhanced Th1 type pro-inflammatory cytokines and inflammatory signaling, elevated oxidative stress, as well as pronounced goblet cell loss. In addition, deficiency in mast cells resulted in enhanced mucosal damage, increased gut permeability, and impaired epithelial tight junctions. Mast cell deficiency was also linked to systemic inflammation, as demonstrated by higher serum levels of tumor necrosis factor \u03b1 and interferon \u03b3 in DKO mice than that in IL-10-deficient mice.",
            "output": [
                "Does mast cell deficiency exacerbate inflammatory bowel symptoms in interleukin-10-deficient mice?"
            ]
        },
        {
            "id": "task847-a2e51938760e45d6845be784223aff6b",
            "input": "Stathmin is a ubiquitous cytosolic regulatory phosphoprotein and is overexpressed in different human malignancies. The main physiological function of stathmin is to interfere with microtubule dynamics by promoting depolymerization of microtubules or by preventing polymerization of tubulin heterodimers. Stathmin plays important roles in regulating many cellular functions as a result of its microtubule-destabilizing activity. Currently, the critical roles of stathmin in cancer cells, as well as in lymphocytes have been valued. This review discusses stathmin and microtubule dynamics in cancer development, and hypothesizes their possible relationship with epithelial-mesenchymal transition (EMT).', 'A PubMed search using such terms as \"stathmin\", \"microtubule dynamics\", \"epithelial-mesenchymal transition\", \"EMT\", \"malignant potential\" and \"cancer\" was performed to identify relevant studies published in English. More than 100 related articles were reviewed.', 'The literature clearly documented the relationship between stathmin and its microtubule-destabilizing activity of cancer development. However, the particular mechanism is poorly understood. Microtubule disruption is essential for EMT, which is a crucial process during cancer development. As a microtubule-destabilizing protein, stathmin may promote malignant potential in cancer cells by initiating EMT.",
            "output": [
                "Does stathmin destabilizing microtubule dynamics promote malignant potential in cancer cells by epithelial-mesenchymal transition?"
            ]
        },
        {
            "id": "task847-b8130d9264b64053836748de0630cb57",
            "input": "The cardiovascular diseases (CVD) are the leading cause of mortality in type 1 diabetes (DM1). Carotid intima-media thickness (IMT) has been approved as a marker of subclinical atherosclerosis. The aim of this prospective study was to evaluate the relationship between baseline diabetic knowledge after five-day teaching program and IMT in patients with (DM1) treated with intensive functional insulin therapy (IFIT) from the onset of the disease.', 'The analysis included 79 subjects aged 23.4 \u00b1 5.1 years with newly diagnosed DM1, participating in Poznan Prospective Study (PoProStu). The patients attended a five-day structured training program in IFIT at diagnosis, followed by a test consisting of 20 questions. After follow-up period of 11 years we evaluated the presence of microangiopathy and subclinical macroangiopathy. IMT of the right common carotid artery was determined using high resolution ultrasonography and calculated automatically with the Carotid Analyzer for Research program.', 'After 11-year follow-up median intima-media thickness was 560 (IQR: 520-630) \u03bcm. We found a negative correlation between diabetes knowledge at baseline and IMT at the end of follow-up (r=-0.27, p=0.017). In multivariate linear regression model baseline diabetic knowledge test result was associated with IMT at follow-up, independently from sex, age, smoking status, presence of hypertension and diabetic kidney disease (all at follow-up) and from mean follow-up LDL-cholesterol concentrations and HbA1c results (\u03b2=-8, 95% CI -16, -1, p=0.037).",
            "output": [
                "Is baseline diabetic knowledge after 5-day teaching program an independent predictor of subclinical macroangiopathy in patients with type 1 diabetes ( Poznan Prospective Study )?"
            ]
        },
        {
            "id": "task847-b9772bd816034a178db4de48dc979ea6",
            "input": "This study used extreme phenotype selection to define two trabecular bone phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular plate-predominant phenotype is more common in Chinese-Americans while the rod-predominant phenotype is more typical of Caucasians. The robustness of these phenotypic associations with respect to lifestyle factors suggests that this trait may have a genetic basis and that these phenotypes can be utilized in future genetic studies.', 'Compared to Caucasians, Chinese-Americans have more plate-like trabecular bone when measured by individual trabecula segmentation (ITS). These findings suggest a phenotypic difference between the races, which may be amenable to genetic analysis. We sought to identify a single ITS plate trait to pursue in genetic studies by conducting an extreme phenotype selection strategy to numerically define two distinct phenotypes-plate-like and rod-like-and determine whether the selected phenotypic associations were independent of lifestyle factors in order to conduct future genetic studies.', 'A previously described cohort of 146 Chinese-American and Caucasian women with high-resolution peripheral quantitative computed tomography imaging and ITS analyses were studied with logistic regression and receiver operator characteristic analyses.', 'The tibial plate-to-rod (TPR) ratio was the best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio phenotypes were defined numerically: plate-like as a TPR ratio value in the highest quartile (\u22651.336) and rod-like as a TPR ratio value in the lowest quartile (\u22640.621). Women with a plate-like phenotype were 25.7 times more likely (95 % CI 7.3-90.1) to be Chinese-American than women with rod-like morphology. After controlling for constitutional and lifestyle covariates, women in the highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7-568.0) to be Chinese-American.",
            "output": [
                "Is a trabecular plate-like phenotype overrepresented in Chinese-American versus Caucasian women?"
            ]
        },
        {
            "id": "task847-d217933999c74f1498a5b2b999aae9b1",
            "input": "Anthropogenic activities cause metal pollution worldwide. Plants can absorb and accumulate these metals through their root system, inducing stress as a result of excess metal concentrations inside the plant. Ethylene is a regulator of multiple plant processes, and is affected by many biotic and abiotic stresses. Increased ethylene levels have been observed after exposure to excess metals but it remains unclear how the increased ethylene levels are achieved at the molecular level. In this study, the effects of cadmium (Cd) exposure on the production of ethylene and its precursor 1-aminocyclopropane-1-carboxylic acid (ACC), and on the expression of the ACC Synthase (ACS) and ACC Oxidase (ACO) multigene families were investigated in Arabidopsis thaliana.', 'Increased ethylene release after Cd exposure was directly measurable in a system using rockwool-cultivated plants; enhanced levels of the ethylene precursor ACC together with higher mRNA levels of ethylene responsive genes: ACO2, ETR2 and ERF1 also indicated increased ethylene production in hydroponic culture. Regarding underlying mechanisms, it was found that the transcript levels of ACO2 and ACO4, the most abundantly expressed members of the ACO multigene family, were increased upon Cd exposure. ACC synthesis is the rate-limiting step in ethylene biosynthesis, and transcript levels of both ACS2 and ACS6 showed the highest increase and became the most abundant isoforms after Cd exposure, suggesting their importance in the Cd-induced increase of ethylene production.",
            "output": [
                "Do cadmium-induced ethylene production and responses in Arabidopsis thaliana rely on ACS2 and ACS6 gene expression?"
            ]
        },
        {
            "id": "task847-dc8dd537e8d84041b7cd0069b1d98d47",
            "input": "To evaluate the influence of environmental enrichment (EE) on memory, cytokines, and brain-derived neurotrophic factor (BDNF) in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy.', 'On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF) or Streptococcus pneumoniae suspension intracisternally at 1 \u00d7 10(6) CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood). EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis.', 'The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF.",
            "output": [
                "Does environmental enrichment restore cognitive deficits induced by experimental childhood meningitis?"
            ]
        },
        {
            "id": "task847-ab6f26fe795e4b4da971dba14112bb2c",
            "input": "Adjuvant chemotherapy improves survival in patients with gastric cancer. However, the relationship between the timing of adjuvant chemotherapy and survival has not been investigated.', 'Patients with D2-resected stage 2 and 3 gastric cancer that received adjuvant chemotherapy from 2005 to 2011 at Yonsei University Health System were included. The patients were grouped according to intervals between surgery and adjuvant chemotherapy.', 'Among 840 patients, the interval from surgery to the start of adjuvant therapy was less than 4 weeks in 337 (40.1 %) patients (early group), 4-8 weeks in 467 (55.6 %) patients (intermediate group), and more than 8 weeks in 36 (4.3 %) patients (late group). The 5-year RFS was 55.7 % in the early group, 54.4 % in the intermediate group, and 43.6 % in the late group (p = 0.076). The corresponding 5-year OS rates were 63.4, 62.8, and 51.7 % (p = 0.037).",
            "output": [
                "Does proper timing of adjuvant chemotherapy affect survival in patients with stage 2 and 3 gastric cancer?"
            ]
        },
        {
            "id": "task847-f80afaf635624ffbab49de91d42ce428",
            "input": "Dexmedetomidine (DEX) has been implicated in modulating the inflammatory response in central nervous system (CNS). However, the mechanism is still poorly understood. In this study, we evaluate the effects of DEX on lipopolysaccharide (LPS)-induced microglia activation and elucidate its possible signaling pathway involved in its anti-inflammatory effects.', 'BV2 and primary microglia were pretreated with various concentrations of DEX (0\u00b701, 0\u00b71, 1, and 10 \u03bcM) and/or PD98059 for 1 hour, then microglia were incubated with LPS (1 \u03bcg/ml) for 24 hours. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were measured by Griess reagent and real-time polymerase chain reaction. Furthermore, two intracellular signaling cascades including extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) were investigated by western blot analysis.', 'Dexmedetomidine significantly attenuated LPS-induced NO production and iNOS expression in both BV2 cells and primary microglial cells. Lipopolysaccharide activated both ERK1/2 and JNK signal pathways; however, DEX exerted a specific inhibitory effect on ERK1/2 rather than JNK. Intriguingly, treatment of primary microglia and BV2 cells with DEX in combination with ERK1/2 inhibitor (PD98059) enhanced attenuation of LPS-induced NO production and iNOS expression.",
            "output": [
                "Does dexmedetomidine inhibit inducible nitric oxide synthase in lipopolysaccharide-stimulated microglia by suppression of extracellular signal-regulated kinase?"
            ]
        },
        {
            "id": "task847-f99f4005db2b466c8ab9888a628c6bcf",
            "input": "Angiopoietin-2, a protein secreted by stimulated endothelium and an antagonist of the endothelium-stabilizing receptor Tie2, contributes to the pathophysiology of septic multiple organ dysfunction. We tested the therapeutic potential of a pulmonary-endothelium-specific RNA interference-based angiopoietin-2 targeting strategy in sepsis.', 'Laboratory and animal research.', 'Research laboratories of the Medical School Hannover, Department of Nephrology and Hypertension, Hannover and Silence Therapeutics GmbH, Berlin.', 'C57Bl/6 mice.', 'Lung-endothelium-specific angiopoietin-2 small interfering RNA was administered both before and after sepsis induction (cecal ligation and puncture or lipopolysaccharides) intravenously.', 'Angiopoietin-2 small interfering RNA was highly specific and reduced angiopoietin-2 expression in the septic murine lungs up to 73.8% (p = 0.01) and enhanced the phosphorylation of Tie2 both in control and septic animals. Angiopoietin-2 small interfering RNA reduced pulmonary interleukin-6 transcription, intercellular adhesion molecule expression, neutrophil infiltration, and vascular leakage. Manifestations of sepsis were also attenuated in distant organs, including the kidney, where renal function was improved without affecting local angiopoietin-2 production. Finally, angiopoietin-2 small interfering RNA ameliorated the severity of illness and improved survival in cecal ligation and puncture, both as a pretreatment and as a rescue intervention.",
            "output": [
                "Does lung-targeted RNA interference against angiopoietin-2 ameliorate multiple organ dysfunction and death in sepsis?"
            ]
        },
        {
            "id": "task847-7b2413b0b5f546d2ab514fa9d6deff2b",
            "input": "Syndromic forms of osteosarcoma (OS) account for less than 10% of all recorded cases of this malignancy. An individual OS predisposition is also possible by the inheritance of low penetrance alleles of tumor susceptibility genes, usually without evidence of a syndromic condition. Genetic variants involved in such a non-syndromic form of tumor predisposition are difficult to identify, given the low incidence of osteosarcoma cases and the genetic heterogeneity of patients. We recently mapped a major OS susceptibility QTL to mouse chromosome 14 by comparing alpha-radiation induced osteosarcoma in mouse strains which differ in their tumor susceptibility.', 'Tumor-specific allelic losses in murine osteosacoma were mapped along chromosome 14 using microsatellite markers and SNP allelotyping. Candidate gene search in the mapped interval was refined using PosMed data mining and mRNA expression analysis in normal osteoblasts. A strain-specific promoter variant in Rb1 was tested for its influence on mRNA expression using reporter assay.', 'A common Rb1 allele derived from the BALB/cHeNhg strain was identified as the major determinant of radiation-induced OS risk at this locus. Increased OS-risk is linked with a hexanucleotide deletion in the promoter region which is predicted to change WT1 and SP1 transcription factor-binding sites. Both in-vitro reporter and in-vivo expression assays confirmed an approx. 1.5 fold reduced gene expression by this promoter variant. Concordantly, the 50% reduction in Rb1 expression in mice bearing a conditional hemizygous Rb1 deletion causes a significant rise of OS incidence following alpha-irradiation.",
            "output": [
                "Does a Rb1 promoter variant with reduced activity contribute to osteosarcoma susceptibility in irradiated mice?"
            ]
        },
        {
            "id": "task847-ab10d29b644e49c7a71e6a44ccb7727d",
            "input": "Androgen receptor (AR) plays an important role in male breast cancer (MBC). Additionally, endocrine therapy is the most important treatment in oestrogen receptor (ER)-positive advanced breast cancer. This study was aimed to investigate the role of AR in MBC treatment and prognosis and to analyse the relationship between AR and the effect of tamoxifen treatment in MBC patients.', 'AR protein levels and other tumour characteristics (e.g. expression of ER (ESR1), PR (PGR), AR, HER2 (ERBB2) and Ki-67 (MKI67)) in breast cancer tissue from 102 MBC patients were determined using immunohistochemical analysis. Additionally, the relationship between AR status and clinicopathological features was analysed using the \u03c7(2)-test. Association with survival was initially analysed using the Kaplan-Meier method and the log-rank test, and Cox regression analysis was used to adjust for other prognostic indicators.', 'High expression of AR was not correlated with T-stage, histological grade, HER2 status and the status of other sex hormone receptors, but was associated with lymph node metastases (P=0.032). AR-positive patients showed significantly shorter 5-year overall survival (OS) rates (P=0.045) and 5-year disease-free survival (DFS) rates (P=0.026) than AR-negative patients. By contrast, for patients who received tamoxifen therapy, AR-negative patients showed a higher clinical benefit rate than AR-positive patients (P=0.025). Additionally, the median TTP and OS were significantly different (P=0.02 for TTP; P=0.029 for OS).",
            "output": [
                "Does androgen receptor expression in male breast cancer predict inferior outcome and poor response to tamoxifen treatment?"
            ]
        },
        {
            "id": "task847-4f25e4efdc14481e9c8c9c613dae58ff",
            "input": "To elucidate the ultrasound (US) features of peripheral nerves including nerve roots in patients with different types of Charcot-Marie-Tooth disease (CMT), and the association between US findings, clinical features and parameters of nerve conduction studies (NCS) in CMT1A.', 'US of median, sural and great auricular nerves and the C6 nerve root was performed in patients with CMT1A (n=20), MPZ-associated CMT (n=3), NEFL-associated CMT (n=4), EGR2-associated CMT (n=1), ARHGEF10-associated CMT (n=1) and in controls (n=30). In patients with CMT1A, we analysed the correlations between US findings and the following parameters: age, CMT Neuropathy Score (CMTNS) and NCS indices of the median nerve.', 'Cross-sectional areas (CSAs) of all the nerves were significantly increased in patients with CMT1A compared with that in controls. In MPZ-associated CMT, increased CSAs were found in the median nerve at wrist and in the great auricular nerve, whereas it was not increased in patients with NEFL-associated CMT. In patients with CMT1A, there was a positive correlation between CMTNS and the CSAs in the median nerves or great auricular nerves. In median nerves in patients with CMT1A, we found a negative correlation between the nerve conduction velocity and the CSA.",
            "output": [
                "Does nerve ultrasound depict peripheral nerve enlargement in patients with genetically distinct Charcot-Marie-Tooth disease?"
            ]
        },
        {
            "id": "task847-1c8a5854269d419882049478bbfe43d9",
            "input": "\u0394Np63, a splice variant of p63, is overexpressed and exhibits oncogenic activity in many cancers including pancreatic and breast cancer and promotes cell survival by inhibiting apoptosis. Despite its role in tumorigenesis, mechanistic activity of \u0394Np63 mediated oncogenic function in osteosarcoma is poorly understood.', 'The expression levels of p63 isoforms in osteosarcoma cell lines were identified using quantitative techniques. Expression profiling using microarray, siRNA mediated loss-of-function, and chromatin immunoprecipitation assays were employed to identify novel \u0394Np63\u03b1 targets in p63-null osteosarcoma SaOS-2 cells that were engineered to express \u0394Np63\u03b1. The phenotype of SaOS-2-\u0394Np63\u03b1 cells was assessed using wound-healing, colony formation, and proliferation assays.', 'The comparative expression analyses identified \u0394Np63\u03b1 as the predominant p63 isoform expressed by invasive OS cell lines. Phenotypic analyses of SaOS-2-\u0394Np63\u03b1 cells in vitro indicate that \u0394Np63\u03b1 imparted tumorigenic attributes upon tumor cells. Further, we show that in osteosarcoma cells \u0394Np63\u03b1 directly regulated the transcription factor GLI2, which is a component of the hedgehog signaling pathway, and that functional interactions between \u0394Np63\u03b1 and GLI2 confer oncogenic properties upon OS cells.",
            "output": [
                "Does \u03b4Np63\u03b1 enhance the oncogenic phenotype of osteosarcoma cells by inducing the expression of GLI2?"
            ]
        },
        {
            "id": "task847-b184c01b6295414e888305b440917bc5",
            "input": "Carriers of balanced translocations are at high risk for unbalanced gametes which can result in recurrent miscarriages or birth defects. Preimplantation genetic diagnosis (PGD) is often offered to select balanced embryos. This selection is currently mainly performed by array CGH on blastomeres. Current methodology does not take into account the phase of the cell cycle, despite the variable copy number status of different genomic regions in S phase.', 'Cell lines derived from 3 patients with different chromosomal imbalances were used to evaluate the accuracy of single cell array CGH. The different cell cycle phases were sorted by flow cytometry and 10 single cells were picked per cell line per cell cycle phase, whole genome amplified and analyzed by BAC arrays, the most commonly used platform for PGD purposes. In contrast to G phase, where the imbalances were efficiently identified, less than half of the probes in the regions of interest indicated the presence of the aberration in 17 S-phase cells, resulting in reduced accuracy.",
            "output": [
                "Is single cell segmental aneuploidy detection compromised by S phase?"
            ]
        },
        {
            "id": "task847-133f6f5e7b7b4ca9912c5e6e048528f7",
            "input": "To analyze whether peroxisome proliferator-activated receptor gamma (PPAR\u03b32) rs1801282 (Pro12Ala) polymorphism is associated with the response to pegylated-interferon-alpha plus ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients, and whether it is able to predict the outcome of HCV treatment.', 'Retrospective follow-up study.', 'Two hundred eighty-five naive patients, who started HCV-treatment, were genotyped for PPAR\u03b32 and interleukin 28B polymorphisms. Genetic data were analyzed under dominant inheritance model. Sustained virological response (SVR) was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment.', 'The variables significantly associated with SVR in a multivariate analysis were HCV-genotype (GT) 3 {adjusted odds ratio [aOR] = 7.66 [95% of confidence interval (95% CI): 3.96 to 14.81] P < 0.001}, HCV-viremia <500,000 IU/mL [aOR = 2.20 (95% CI: 1.16 to 4.15] P = 0.015), no/mild liver fibrosis (F < 2) [aOR = 1.92 (95% CI: 1.08 to 3.42) P = 0.026], IL28B rs12980275 AA genotype [aOR = 2.70 (95% CI: 1.54 to 4.71) P < 0.001], and PPAR\u03b32 rs1801282 CG/GG genotype [aOR = 2.93 (95% CI: 1.27 to 6.72) P = 0.011]. When PPAR\u03b32 rs1801282 genotype was included in a decision tree analysis, HCV-GT3 patients with CG/GG genotype had increased SVR from 80.3% to 100%. In GT1/4 patients, rs12980275 AA carriers had increased SVR from 58.7% to 78.6%, and rs12980275 AG/GG carriers had increased SVR from 28.7% to 35.7%. The overall percentage of patients correctly classified was 71.6% and the area under the receiver operating characteristic curves was 0.766 \u00b1 0.028.",
            "output": [
                "Is pPAR\u03b32 Pro12Ala polymorphism associated with sustained virological response in HIV/HCV-coinfected patients under HCV therapy?"
            ]
        },
        {
            "id": "task847-107dfbfa92b743479e1c6528d6b99cc8",
            "input": "Interindividual variability and drug interaction studies suggest that blood-brain barrier drug transporters mediate human methadone brain biodistribution. In vitro and animal studies suggest that methadone is a substrate for the efflux transporter P-glycoprotein, and that P-glycoprotein-mediated transport influences brain access and pharmacologic effect. This investigation tested whether methadone is a transporter substrate in humans [corrected].', 'Healthy volunteers received oral (N=16) or IV (N=12) methadone in different crossover protocols after nothing (control) or the validated P-glycoprotein inhibitor cyclosporine (4.5 mg/kg orally twice daily for 4 days, or 5 mg/kg IV over 2 h). Plasma and urine methadone and metabolite concentrations were measured by mass spectrometry. Methadone effects were measured by miosis and thermal analgesia (maximally tolerated temperature and verbal analog scale rating of discreet temperatures).', 'Cyclosporine marginally but significantly decreased methadone plasma concentrations and apparent oral clearance, but had no effect on methadone renal clearance or on hepatic N-demethylation. Cyclosporine had no effect on miosis or on R-methadone concentration-miosis relationships after either oral or IV methadone. Peak miosis was similar in controls and cyclosporine-treated subjects after oral methadone (1.4\u00b10.4 and 1.3\u00b10.5 mm/mg, respectively) and IV methadone (3.1\u00b11.0 and 3.2\u00b10.8 mm, respectively). Methadone increased maximally tolerated temperature, but analgesia testing was confounded by cyclosporine-related pain.",
            "output": [
                "Does cyclosporine-inhibitable cerebral drug transport influence clinical methadone pharmacodynamics?"
            ]
        },
        {
            "id": "task847-8c0b7d7420ac4ef2bf00af456385409c",
            "input": "To assess the accuracy of the clinically estimated blood loss (EBL) when compared with the actual blood loss (ABL) in replacement surgeries.', \"This prospective study was done in Sri Ramachandra Medical Centre from April 2011 to April 2013. Altogether 140 patients undergoing total hip replacement or total knee replacement were included with the inclusion criteria being patients with haemoglobin higher than 100 g/ml and coagulation profile within normal limits. Exclusion criteria were intake of anti-platelet drug or anti-coagulant, bleeding disorders, thrombotic episode, and haematological disorders. There were 65 men and 75 women. In this study, the consultants were free to use any clinical method to estimate the blood loss, including counting the blood-soaked mops and gauze pieces (estimating the volume of blood carried in all the mops and gauzes), measuring blood lost to suction bottles and blood in and around the operative field. The ABL was calculated based on a modification of the Gross's formula using haematocrit values.\", 'In 42 of the 140 cases, the EBL exceeded the ABL. These cases had a negative difference in blood loss (or DIFF-BL<0) and were included in the overestimation group, which accounted for 30% of the study population. Of the remaining 98 cases (70%), the ABL exceeded the EBL. Therefore they were put into the underestimation group who had a positive difference in blood loss (DIFF-BL>0). We found that when the average blood loss was small, the accuracy of estimation was high. But when the average blood loss exceeded 500 ml, the accuracy rate decreased significantly. This suggested that clinical estimation is inaccurate with the increase of blood loss.",
            "output": [
                "Do surgeons often underestimate the amount of blood loss in replacement surgeries?"
            ]
        },
        {
            "id": "task847-068a4333ecab4e12b284e012ed5ad546",
            "input": "Oncolytic viruses represent a promising therapy against cancers with acquired drug resistance. However, low efficacy limits its clinical application. The objective of this study is to investigate whether pharmacologically modulating autophagy could enhance oncolytic Newcastle disease virus (NDV) strain NDV/FMW virotherapy of drug-resistant lung cancer cells.', 'The effect of NDV/FMW infection on autophagy machinery in A549 lung cancer cell lines resistant to cisplatin (A549/DDP) or paclitaxel (A549/PTX) was investigated by detection of GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) puncta, formation of double-membrane vesicles and conversion of the nonlipidated form of LC3 (LC3-I) to the phosphatidylethanolamine-conjugated form (LC3-II). The effects of autophagy inhibitor chloroquine (CQ) and autophagy inducer rapamycin on NDV/FMW-mediated antitumor activity were evaluated both in culture cells and in mice bearing drug-resistant lung cancer cells.', 'We show that NDV/FMW triggers autophagy in A549/PTX cells via dampening the class I PI3K/Akt/mTOR/p70S6K pathway, which inhibits autophagy. On the contrary, NDV/FMW infection attenuates the autophagic process in A549/DDP cells through the activation of the negative regulatory pathway. Furthermore, combination with CQ or knockdown of ATG5 significantly enhances NDV/FMW-mediated antitumor effects on A549/DDP cells, while the oncolytic efficacy of NDV/FMW in A549/PTX cells is significantly improved by rapamycin. Interestingly, autophagy modulation does not increase virus progeny in these drug resistant cells. Importantly, CQ or rapamycin significantly potentiates NDV/FMW oncolytic activity in mice bearing A549/DDP or A549/PTX cells respectively.",
            "output": [
                "Does pharmacological modulation of autophagy enhance Newcastle disease virus-mediated oncolysis in drug-resistant lung cancer cells?"
            ]
        },
        {
            "id": "task847-685b1e57b05245b2ab02982a1002b3f1",
            "input": "To investigate the effectiveness of a suture bridge technique for quadriceps tendon rupture repair in uraemic patients.', 'Between March 2010 and September 2012, 10 uraemic patients (14 sides) with quadriceps tendon rupture were treated with the suture bridge technique. Of them, 8 were male and 2 were female, aged from 30 to 62 years (mean, 54.2 years). The duration of uremia was 3-11 years (mean, 5.5 years): the duration of quadriceps tendon rupture was 5 days to 2 months (median, 12 days). Six cases had a trauma history, and one case had diabetes. The left side was involved in 2 cases, the right side in 4 cases, and both sides in 4 cases. The active range of motion (ROM) of the knees was (115.0 +/- 8.3) degrees in flexion, and (72.5 +/- 21.2) degrees in extension. Lysholm score was 19.5 +/- 16.3. X-ray films showed downward shifting of patella. MRI revealed discontinuity between distal quadriceps tendon and upper pole of patella.', 'The operation time was 30-50 minutes (mean, 40.3 minutes). Primary healing of incision was obtained in all patients without complications. All patients were followed up 12-25 months (mean, 16.3 months). There was no re-rupture of quadriceps tendon or loosening of internal fixation during follow-up. At last follow-up, the active ROM of the knees was (121.0 +/- 7.9) degrees in flexion, showing no significant difference when compared with preoperative one (t = -2.075, P =0.058); the active ROM was (8.2 +/- 6.1) degrees in extension, showing significant difference when compared with preoperative one (t = 11.702, P = 0.000). Lysholm score was 84.6 +/- 12.4, showing significant difference when compared with preoperative score (t = -16.226, P = 0.000). According to the American Knee Society score (KSS), the results were excellent in 4 sides, good in 9 sides, and fair in 1 side, and the total excellent and good rate was 92.9%. At last follow-up, the active ROM of the knee, Lysholm score, and KSS score were significantly better in young patients (< 45 years) than in elder patients (> or = 45 years), and in patients receiving early operation (< 2 weeks) than in patients receiving late operation (> or = 2 weeks) (P < 0.05).",
            "output": [
                "Do [ Effectiveness of a suture bridge technique for repair of quadriceps tendon rupture in uraemic patients ]?"
            ]
        },
        {
            "id": "task847-60ef440c452d462b95077badf79790dd",
            "input": "Cardiac allograft vasculopathy is the leading cause of graft failure and death in heart transplant (HTx) recipients; however, the association between the etiology of heart failure (ischemic cardiomyopathy [ICM] or non-ICM) that led to HTx and progression of cardiac allograft vasculopathy, and adverse events after HTx has not been explored.', 'We retrospectively included 165 HTx patients, who were followed-up with at least 2 virtual histology-intravascular ultrasound examinations after HTx, and grouped them as ICM (n=46) or non-ICM (n=119). Coronary artery plaque volume was analyzed using virtual histology-intravascular ultrasound, and cardiovascular event data-a composite of myocardial infarction, hospitalization for heart failure and arrhythmia, revascularization, retransplantation, and death including cardiovascular death-were collected from the medical records of all study subjects. ICM patients had significantly higher plaque volume at both first (P=0.040) and follow-up (P=0.015) intravascular ultrasound examinations. After multivariate adjustment for traditional coronary risk factors, ICM was significantly associated with plaque progression (odds ratio 3.10; CI 1.17 to 9.36; P=0.023). Ten-year cardiovascular event-free survival was 50% in ICM patients compared with 84% in non-ICM patients (log-rank test P=0.003). In multivariate Cox proportional hazard analysis, ICM was significantly associated with a higher event rate after HTx (hazard ratio 2.02; 95% CI 1.01 to 4.00; P=0.048).",
            "output": [
                "Is ischemic cardiomyopathy associated with coronary plaque progression and higher event rate in patients after cardiac transplantation?"
            ]
        },
        {
            "id": "task847-51bebeadcca8498bb6a8f8e5a85dc5bc",
            "input": "The aim of this study was to investigate the smoking status of lung cancer patients and to confirm the risk of smoking for patients undergoing lung cancer surgery.', 'We conducted a retrospective study of patients undergoing lung cancer surgery. Between May 2004 and March 2013, 716 patients underwent lung cancer surgery at our institution. Based on smoking status, the patients were classified into 3 groups: nonsmoker, past smoker, and current smoker. Based on exclusion criteria, a final total of 670 patients were investigated for the association between smoking status and postoperative complications. In addition, we explored the effect of smoking on survival after surgery.', 'There were 254 non-smokers, 246 past smokers, and 170 current smokers. The percent of female patients, adenocarcinoma, and stage IA cancer was highest in the nonsmokers. Respiratory function was significantly impaired in past and current smokers. Respiratory and cardiac complications were found less frequently in non-smokers (11.4%) followed by 17.1% of past smokers and 21.2% of current smokers (p = 0.0226). Univariate analysis showed that smoking was a significantly poor prognostic factor for overall survival. The 5-year survival rates for non-smokers, past, and current smokers were 81.4, 65.4, and 68.8%, respectively (p = 0.0003).",
            "output": [
                "Is smoking a perioperative risk factor and prognostic factor for lung cancer surgery?"
            ]
        },
        {
            "id": "task847-39a0aa6741f049709893bb6bea5eacdd",
            "input": "Infection with Helicobacter pylori is the strongest known risk factor for adenocarcinoma of the stomach. Tumorigenic transformation of gastric epithelium induced by H. pylori is a highly complex process driven by an active interplay between bacterial virulence and host factors, many aspects of which remain obscure. In this work, we investigated the degradation of p53 tumour suppressor induced by H. pylori.', 'Expression of p53 protein in gastric biopsies was assessed by immunohistochemistry. Gastric cells were co-cultured with H. pylori strains isolated from high-gastric risk and low-gastric risk areas and assessed for expression of p53, p14ARF and cytotoxin-associated gene A (CagA) by immunoblotting. siRNA was used to inhibit activities of ARF-BP1 and Human Double Minute 2 (HDM2) proteins.', 'Our analysis demonstrated that H. pylori strains expressing high levels of CagA virulence factor and associated with a higher gastric cancer risk more strongly suppress p53 compared with low-risk strains in vivo and in vitro. We found that degradation of p53 induced by bacterial CagA protein is mediated by host HDM2 and ARF-BP1 E3 ubiquitin ligases, while the p14ARF protein counteracts H. pylori-induced signalling.",
            "output": [
                "Does bacterial CagA protein induce degradation of p53 protein in a p14ARF-dependent manner?"
            ]
        },
        {
            "id": "task847-72714389267b4ff19244b77fe1e4c614",
            "input": "Vitamin D and the vitamin D receptor (VDR) appear to be important immunological regulators of inflammatory bowel diseases (IBD). Defective autophagy has also been implicated in IBD, where interestingly, polymorphisms of genes such as ATG16L1 have been associated with increased risk. Although vitamin D, the microbiome and autophagy are all involved in pathogenesis of IBD, it remains unclear whether these processes are related or function independently.', 'We investigated the effects and mechanisms of intestinal epithelial VDR in healthy and inflamed states using cell culture models, a conditional VDR knockout mouse model (VDR(\u0394IEC)), colitis models and human samples.', 'Absence of intestinal epithelial VDR affects microbial assemblage and increases susceptibility to dextran sulfate sodium-induced colitis. Intestinal epithelial VDR downregulates expressions of ATG16L1 and lysozyme, and impairs antimicrobial function of Paneth cells. Gain and loss-of-function assays showed that VDR levels regulate ATG16L1 and lysozyme at the transcriptional and translational levels. Moreover, low levels of intestinal epithelial VDR correlated with reduced ATG16L1 and representation by intestinal Bacteroides in patients with IBD. Administration of the butyrate (a fermentation product of gut microbes) increases intestinal VDR expression and suppresses inflammation in a colitis model.",
            "output": [
                "Does intestinal epithelial vitamin D receptor deletion lead to defective autophagy in colitis?"
            ]
        },
        {
            "id": "task847-039913cb6d764af6a2e1bbc6d1262b26",
            "input": "It is known that enhancement of sympathetic nerve activity based on a decrease in parasympathetic nerve activity is associated with fatigue induced by mental tasks lasting more than 30 min. However, to measure autonomic nerve function and assess fatigue levels in both clinical and industrial settings, shorter experimental durations and more sensitive measurement methods are needed. The aim of the present study was to establish an improved method for inducing fatigue and evaluating the association between it and autonomic nerve activity.', 'Twenty-eight healthy female college students participated in the study. We used a kana pick-out test (KPT) as a brief verbal cognitive task and recorded electrocardiography (ECG) to measure autonomic nerve activity. The experimental design consisted of a 16-min period of ECG: A pre-task resting state with eyes open for 3 min and eyes closed for 3 min, the 4-min KPT, and a post-task resting state with eyes open for 3 min and eyes closed for 3 min.', 'Baseline fatigue sensation, measured by a visual analogue scale before the experiment, was associated with the decrease in parasympathetic sinus modulation, as indicated the by ratio of low-frequency component power (LF) to high-frequency component power (HF), during the KPT. The LF/HF ratio during the post-KPT rest with eyes open tended to be greater than the ratio during the KPT and correlated with fatigue sensation. Fatigue sensation was correlated negatively with log-transformed HF, which is an index of parasympathetic sinus modulation, during the post-KPT rest with eyes open.",
            "output": [
                "Does fatigue correlate with the decrease in parasympathetic sinus modulation induced by a cognitive challenge?"
            ]
        },
        {
            "id": "task847-98e2ba7ea0db4b229df72ead4ee9d17f",
            "input": "Although few studies have examined cardiovascular disease in Asian-American subgroups separately, limited data in Asian Americans strongly suggest that some subgroups are at increased risk. The present study examined modifiable cardiovascular risk factor profiles as a function of Asian ethnicity.', 'This descriptive cross-sectional pilot study recruited Asian-American women (N=147) in northeast Florida including Cambodians (n=39), Chinese (n=36), Filipinos (n=49), and Vietnamese (n=23). Risk factors included blood pressure, body mass index, waist circumference and blood lipids.', 'Filipino participants (41%) had \u22654 risk factors compared to 21% Cambodian, 13% Vietnamese and 0% Chinese. The Chinese had significantly more participants (44%) with the absence of CVD risk factors compared to all other subgroups. Obesity rate (18%), mean BMI: 26 \u00b1 5 kg/m(2) and mean triglycerides (173 \u00b1 103 mg/dL) were highest in Filipinas (n=49). The Chinese (n=36) had a low rate (4%) of obesity with a mean BMI of 23 \u00b1 3 kg/m(2) and the least risk factors along with the lowest triglycerides (88 \u00b1 44 mg/dL). Cambodians (n=39; BMI of 24 \u00b1 3 kg/m(2)) and Vietnamese (n=23; BMI: 22 \u00b1 3 kg/m(2)) had low rates of obesity with comparable rates of unhealthy lipids and hypertension as the Filipinas.",
            "output": [
                "Does one size fit all : cardiovascular health disparities as a function of ethnicity in Asian-American women?"
            ]
        },
        {
            "id": "task847-9f813fb55de748d1bedc53195ecec4b2",
            "input": "To determine whether the CT angiography (CTA) spot sign marks bleeding complications during and after surgery for spontaneous intracerebral hemorrhage (ICH).', 'In a 2-center study of consecutive spontaneous ICH patients who underwent CTA followed by surgical hematoma evacuation, 2 experienced readers (blinded to clinical and surgical data) reviewed CTAs for spot sign presence. Blinded raters assessed active intraoperative and postoperative bleeding. The association between spot sign and active intraoperative bleeding, postoperative rebleeding, and residual ICH volumes was evaluated using univariable and multivariable logistic regression.', 'A total of 95 patients met inclusion criteria: 44 lobar, 17 deep, 33 cerebellar, and 1 brainstem ICH; \u22651 spot sign was identified in 32 patients (34%). The spot sign was the only independent marker of active bleeding during surgery (odds ratio [OR] 3.4; 95% confidence interval [CI] 1.3-9.0). Spot sign (OR 4.1; 95% CI 1.1-17), female sex (OR 6.9; 95% CI 1.7-37), and antiplatelet use (OR 4.6; 95% CI 1.2-21) were predictive of postoperative rebleeding. Larger residual hematomas and postoperative rebleeding were associated with higher discharge case fatality (OR 3.4; 95% CI 1.1-11) and a trend toward increased case fatality at 3 months (OR 2.9; 95% CI 0.9-8.8).",
            "output": [
                "Does cT angiography spot sign in intracerebral hemorrhage predict active bleeding during surgery?"
            ]
        },
        {
            "id": "task847-a3ff97f5956f40d29d9f3322dbc5d024",
            "input": "We hypothesised that short-term application of bi-level nasal continuous positive airway pressure CPAP (SiPAP) compared with conventional nasal CPAP (nCPAP) at the same mean airway pressure in infants with persistent oxygen need recovering from respiratory distress syndrome would improve CO2 removal with no change in oxygen requirement.', 'Non-blinded, randomised, observational four-period crossover study.', 'Level III NICU; low-birthweight infants requiring CPAP and oxygen while recovering from respiratory distress syndrome.', 'Infants requiring nasal CPAP for >24\\u2005h prior to study enrolment, and fraction of inspired oxygen requirement (FiO2) of 0.25-0.5, were randomised to either nCPAP or SiPAP. A crossover design with four 1 h treatment periods was used such that each infant received both treatments twice. Oxygen saturations (SaO2), transcutaneous CO2 (tcCO2) and vital signs were monitored continuously. Polysomnographic recordings were analysed for apnoea, bradycardia and oxygen desaturation.', 'Twenty low-birthweight infants receiving 0.3\u00b10.04% supplemental oxygen on CPAP of 6 cm H2O were studied at an average of 33\\u2005days of age (\u00b123\\u2005days, SD). There were no differences in tcCO2 or other physiological parameters except mean blood pressure, which was lower during nCPAP (52.3\u00b18.3 vs 54.4\u00b19.1\\u2005mm\\u2005Hg; \u00b1SD; p<0.01). No differences in short or prolonged apnoea, bradycardia or significant desaturation events were observed.",
            "output": [
                "Does bi-level CPAP improve gas exchange when compared with conventional CPAP for the treatment of neonates recovering from respiratory distress syndrome?"
            ]
        },
        {
            "id": "task847-74e4158428e442b3a794edf99428c559",
            "input": "High mobility group box 1 (HMGB1) is a late mediator of systemic inflammation. Extracellular HMGB1 play a central pathogenic role in critical illness. The purpose of the study was to investigate the association between plasma HMGB1 concentrations and the risk of poor outcomes in patients with severe blunt chest trauma.', 'The plasma concentrations of HMGB1 in patients with severe blunt chest trauma (AIS\\u2009\u2265\\u20093) were measured by a quantitative enzyme-linked immunosorbent assay at four time points during seven days after admission, and the dynamic release patterns were monitored. The biomarker levels were compared between patients with sepsis and non-sepsis, and between patients with multiple organ dysfunction syndrome (MODS) and non-MODS. The related factors of prognosis were analyzed by using multivariate logistic regression analysis. The short-form 36 was used to evaluate the quality of life of patients at 12 months after injury.', 'Plasma HMGB1 levels were significantly higher both in sepsis and MODS group on post-trauma day 3, 5, and 7 compared with the non-sepsis and non-MODS groups, respectively. Multivariate analysis showed that HMGB1 levels and ISS were independent risk factors for sepsis and MODS in patients with severe blunt chest trauma.",
            "output": [
                "Is high plasma levels of high mobility group box 1 associated with the risk of sepsis in severe blunt chest trauma patients : a prospective cohort study?"
            ]
        },
        {
            "id": "task847-0b495ecfcacc4f12938f1e7b1fe7fd93",
            "input": "The AID/APOBECs are deaminases that act on cytosines in a diverse set of pathways and some of them have been linked to the onset of genetic alterations in cancer. Among them, APOBEC1 is the only family member to physiologically target RNA, as the catalytic subunit in the Apolipoprotein B mRNA editing complex. APOBEC1 has been linked to cancer development in mice but its oncogenic mechanisms are not yet well understood.', 'We analyze whether expression of APOBEC1 induces a mutator phenotype in vertebrate cells, likely through direct targeting of genomic DNA. We show its ability to increase the inactivation of a stably inserted reporter gene in a chicken cell line that lacks any other AID/APOBEC proteins, and to increase the number of imatinib-resistant clones in a human cellular model for chronic myeloid leukemia through induction of mutations in the BCR-ABL1 fusion gene. Moreover, we find the presence of an AID/APOBEC mutational signature in esophageal adenocarcinomas, a type of tumor where APOBEC1 is expressed, that mimics the one preferred by APOBEC1 in vitro.",
            "output": [
                "Does the RNA editing enzyme APOBEC1 induce somatic mutations and a compatible mutational signature is present in esophageal adenocarcinomas?"
            ]
        },
        {
            "id": "task847-7b67954f1623492cb3d7a80fb85cff5d",
            "input": "Despite evidence supporting the importance of breastfeeding to child health, breastfeeding practices remain suboptimal in Vietnam. There is currently little evidence on the importance of breastfeeding in the prevention of morbidity during infancy in Vietnam. In order to provide country specific data for policy makers to support breastfeeding friendly policies and programs, analysis was undertaken on a cross-sectional dataset to investigate the association between breastfeeding practices and prevalence of diarrhea and acute respiratory infection (ARI) among infants aged 0-5 months.', 'Data on socio-demographic characteristics, infant feeding practices and prevalence of diarrhea and ARI were obtained from 6,068 mother-child dyads in 11 provinces of Vietnam in 2011. Multivariate logistic regression was used to examine the associations between breastfeeding practices and child illnesses.', 'On average, the prevalence of diarrhea and ARI among infants 0-5 months was 5.3% and 24.5%, respectively. Though half of all infants were breastfed within one hour of birth, 73.3% were given prelacteal foods in the first three days after birth. Only 20.2% of children 0-5 months old were exclusively breastfed, while 32.4% were predominantly breastfed and 47.4% partially breastfed. After adjusting for confounders, early initiation of breastfeeding was associated with lower prevalence of diarrhea [adjusted odds ratio (AOR)\\u2009=\\u20090.74 (95% CI 0.58, 0.93)], while prelacteal feeding was associated with higher prevalence [AOR\\u2009=\\u20091.53 (95% CI 1.15, 2.03)]. Compared to infants who were exclusively breastfed, infants who were predominantly [AOR\\u2009=\\u20091.52 (95% CI 1.05, 2.21)] or partially breastfed [AOR\\u2009=\\u20091.55 (95% CI 1.07, 2.24)] were more likely to have diarrhea. Prelacteal feeding [AOR\\u2009=\\u20091.16 (95% CI 1.01, 1.33)] and partial breastfeeding [AOR relative to exclusive breastfeeding\\u2009=\\u20091.24 (95% CI 1.03, 1.48)] were associated with higher prevalence of ARI. While the protective effects of exclusive breastfeeding against diarrhea declined with child age, this effect for ARI appears to have remained constant.",
            "output": [
                "Are suboptimal breastfeeding practices associated with infant illness in Vietnam?"
            ]
        },
        {
            "id": "task847-8332b3290fa44092a1e98271de4a6ec2",
            "input": "Allergic rhinitis is a morbid condition that is frequently overlooked by patients and physicians. This type of atopy has not been adequately investigated in the United Arab Emirates.', 'This cross-sectional, population-based observational study was conducted in the seven Emirates (Abu Dhabi, Dubai, Sharjah, Ajman, Umm Al-Quwain, Ras Al-Khaimah, and Fujairah). It used the European Community Respiratory Health Survey (ECRHS II) to screen for allergic rhinitis in people living in this region.', 'Symptoms of allergic rhinitis were present in 85 (7%) of the 1,229 study population. Only 33 (39%) patients received treatment. Seventy-six (89%) patients had asthma. Thirty-seven (44%) patients were poly-sensitized. Symptoms were aggravated by dust (59%), grass/pollens (44%) and proximity to animals (21%). Winter was the peak season (37%), followed by spring (30%), autumn (18%) and summer (15%). Grass/pollen allergies were clustered in the winter, spring and summer (p\\u2009\u2264\\u20090.001). Dust was non-seasonal (p\\u2009\u2265\\u20090.121) and animal allergy was worse in the winter (p\\u2009=\\u20090.024) and spring (p\\u2009=\\u20090.044). Spring symptoms were less common in people living in the inner city (p\\u2009=\\u20090.003).",
            "output": [
                "Does prevalence and trigger of allergic rhinitis in the United Arab Emirates?"
            ]
        },
        {
            "id": "task847-a7405b5ddc1541e69dd664e1195ddb65",
            "input": "Late onset asthma is associated with more severe disease and higher morbidity than in younger asthma patients. This may in part relate to under recognition of asthma in older adults, but evidence on the impact of patient age on diagnostic assessment of asthma in a specialist setting is sparse.', 'To examine the impact of patient age on the type and proportion of diagnostic tests performed in patients undergoing specialist assessment for asthma.', 'Data from a clinical population consisting of all patients consecutively referred over a 12 months period to a specialist clinic for assessment of asthma were analysed.', 'A total of 224 patients with asthma or suspected asthma were referred during the 12 month period; 86 adults aged <35 years, 95 aged 35-55 years and 43 aged >55 years. Symptom characteristics were similar, but adults >35 years had a lower lung function than younger adults, and were more frequently smokers. However, a regression analysis showed that older age was associated with a lower likelihood of diagnostic assessment with a reversibility test, a bronchial challenge test, or measurement of exhaled NO, independently of a known diagnosis of asthma, smoking habits and lung function at referral.",
            "output": [
                "Is the level of specialist assessment of adult asthma influenced by patient age?"
            ]
        },
        {
            "id": "task847-2a0e38ffaee047e1aea1fdf5a2ea07f4",
            "input": "A functional vacuolar adenosine triphosphatase (v-ATPase) complex regulates canonical Wnt/\u03b2-catenin signaling. The goal of this study was to identify the distribution of the v-ATPase in human and murine models of pancreatic intraepithelial neoplasms (PanINs) and assess its role in Wnt/\u03b2-catenin signaling.', 'We evaluated the immunolabeling pattern of the v-ATPase in human PanIN specimens and murine PanIN-1 and PanIN-2 lesions obtained from Ptf1a(Cre/+); LSL-Kras(G12D) mice. Wnt/\u03b2-catenin signaling was interrogated in primary PanIN cells by examining the phosphorylated levels of its surface coreceptor, low-density lipoprotein receptor-related protein-6 (LRP6), and its intracellular effector, nonphosphorylated \u03b2-catenin. The response of primary PanIN cells to epidermal growth factor (EGF) was assessed in the absence and presence of the v-ATPase inhibitor, concanamycin.', 'In advanced (PanIN-2), but not early (PanIN-1), lesions, the v-ATPase assumed a polarized phenotype. Blocking the v-ATPase disrupted Wnt/\u03b2-catenin signaling in primary PanIN cells despite significantly higher levels of the total and activated Wnt cell surface coreceptor, LRP6. Vacuolar adenosine triphosphatase blockade significantly decreased the total and activated levels of EGF receptor, a determinant of PanIN progression. The activation of EGF receptor and its intracellular mediator, p44/42 mitogen-activated protein kinase, was also reduced by v-ATPase blockade. This led to diminished proliferation in response to EGF ligand.",
            "output": [
                "Does polarization of the vacuolar adenosine triphosphatase delineate a transition to high-grade pancreatic intraepithelial neoplasm lesions?"
            ]
        },
        {
            "id": "task847-9f4a999429794473b31d592e9532c8af",
            "input": "The aim of this study was to investigate the rate, longitudinal improvement, and risk factors of sleep disturbance after 4 common orthopaedic traumatic conditions.', 'The functional status of 1095 patients was prospectively assessed using validated questionnaires for patients with acute proximal humerus (n = 111), distal radius (n = 440), tibial plateau (n = 109), and ankle fractures (n = 435). Patient reported sleep difficulty was compared with the overall functional and emotional status of each patient at 3, 6, and 12 months after treatment.', 'Sleep difficulty at 3-month follow-up was reported in 41% of patients with proximal humerus fracture, 25% of patients with distal radius fracture, 36% of patients with tibial plateau, and 19% of patients with ankle fracture. By 12-month follow-up, less than 20% of patients with all fracture types reported sleep difficulty. At 12-month follow-up, the SF-36 Mental Health category for patients with distal radius fractures (P = 0.001) and the Short Musculoskeletal Function Assessment Emotional category for patients with tibial plateau fractures (P = 0.024) and ankle fractures (P \u2264 0.001) were independent predictors of poor sleep, whereas the respective functional status categories were not.",
            "output": [
                "Is sleep disturbance after fracture related to emotional well-being rather than functional result?"
            ]
        },
        {
            "id": "task847-6254400c7ec64bec99bece173305dc52",
            "input": "Considering the characterization of vitamin D deficiency as a risk factor of ectopic fat deposition, the association of serum 25-hydroxy vitamin D3 [25(OH)D3] levels with non-alcoholic fatty liver disease (NAFLD) was evaluated in Chinese men with normal body mass index (BMI) and enzyme markers of liver function.', 'A total of 514 participants (22 to 79 years old) with normal BMI and liver enzymes were identified for analysis. Abdominal ultrasound was performed to diagnose NAFLD, and the fatty liver index (FLI) was calculated to quantify liver steatosis. Serum 25(OH)D3 levels were determined by an electrochemiluminescence immunoassay.', 'Among the entire study population, the mean levels of serum 25(OH)D3 were 15.32\u00b15.77 ng/mL. However, when serum 25(OH)D3 levels were compared between non-NAFLD subjects (n=438) and NAFLD subjects (n=76), the latter showed significantly lower levels (15.65\u00b15.89 ng/mL vs 13.46\u00b14.65 ng/mL, P=0.002). In addition, serum 25(OH)D3 levels were found to be significantly correlated with FLI after adjustment for age and BMI (r=-0.108, P=0.014). Logistic regression showed that serum 25(OH)D3 levels were independently correlated with NAFLD (OR: 0.937, 95% CI: 0.884-0.993, P=0.028). Furthermore, stepwise regression analysis revealed that serum 25(OH)D3 levels were inversely associated with FLI (\u03b2=-0.055, P=0.040).",
            "output": [
                "Is serum vitamin D associated with non-alcoholic fatty liver disease in Chinese males with normal weight and liver enzymes?"
            ]
        },
        {
            "id": "task847-3bc5504378e5451499d3145a22e8d1be",
            "input": "Honey has been familiar to possess antimicrobial potential to clear infection against burn wound infecting bacteria since ancient times. The objective of the study was to evaluate the efficacy of the newly formulated honey ointment during the treatment of burn wound infections. The Experimental (Non comparative) study was conducted at outpatient department of Dermatology, Fauji Foundation Hospital, Rawalpindi from November 2009 to October 2010.', 'The antimicrobial activity of different Pakistani floral sources (Acacia nilotica species indica, Zizyphus, Helianthus annuus and Carisa opaca) honey samples were investigated by disc diffusion method against freshly isolated burn wounds infecting bacteria. Ointment containing 20% active antimicrobial honey was formulated as a sovereign remedy. A total number of twenty patients with second degree of burn wounds on different parts of the body were studied. A thin layer of honey ointment on gauze was applied to the wounds two to three times a day up to the complete healing.', 'During microbiological study, Pakistani honey samples were discovered to exhibit a very promising antimicrobial activity against all the wound infecting microorganisms tested. Clinical trials demonstrated that the topical application of honey ointment have significant control of infections arising form pathogenic bacteria and up to 100% healing results were observed in all burn wound cases within mean healing time for the duration of 8.15 (3-18) days time period.",
            "output": [
                "Do efficacy of newly formulated ointment containing 20 % active antimicrobial honey in treatment of burn wound infections?"
            ]
        },
        {
            "id": "task847-172a4254ac884da6a741a9071f5c2f8d",
            "input": "To compare histologically the size and appearance of capsule disks after femtosecond laser-assisted cataract surgery and conventional cataract surgery.', 'In 100 eyes of 100 patients with visually significant cataracts, a femtosecond laser capsulotomy or a capsulorhexis with an aimed diameter of 5.0 mm was performed by one experienced surgeon. The diameter, area, circularity, and cut quality was histologically examined with light microscopy and scanning electron microscopy.', 'The mean diameter of the manual and the femtosecond laser capsule disk group were not statistically significantly different (manual 4.91 \u00b1 0.34; femtosecond: 4.93 \u00b1 0.03; p = 0.58). The mean area of the capsule disks was 18.85 \u00b1 2.69 mm2 in the manual and 19.03 \u00b1 0.26 mm2 in the femtosecond group (p = 0.64). The capsules of the femtosecond group (0.95 \u00b1 0.02) were significantly more circular than the ones of the manual group (0.81 \u00b1 0.07; p&lt;0.0001). The femtosecond laser capsule disks displayed a more saw blade-like structure created through the single laser spots. The histologic examination combined with prospective video analysis revealed respiratory movement of the eye during the capsulotomy as a potential risk factor for redial tears.",
            "output": [
                "Does histologic evaluation of in vivo femtosecond laser-generated capsulotomies reveal a potential cause for radial capsular tears?"
            ]
        },
        {
            "id": "task847-c27d3a98ee0e4ebd9326c03e7cd7db8f",
            "input": "This pilot study, the first of its type, was conducted to determine the clinical outcome of glaucoma drainage implant (GDI) surgery supplemented with injectable crosslinked hyaluronic acid (HA) in patients with severe glaucoma.', 'This was a retrospective chart study involving 10 eyes of 10 patients with severe glaucoma (glaucomatous visual field loss worse than -20 dB) who had previously undergone GDI surgery supplemented with crosslinked HA with a 2-year follow-up. Surgical success was defined as intraocular pressure (IOP) &lt;21 mm Hg with a reduction of \u226540% (definition A) or \u226550% (definition B) from baseline IOP on 2 consecutive follow-up visits, IOP &gt;5 mm Hg on 2 consecutive follow-up visits, and neither reoperation of glaucoma nor loss of light perception vision.', 'The mean \u00b1 SD baseline IOP before GDI was 38.5 \u00b1 10.7 mm Hg, and the mean IOP at the last follow-up visit was 13.0 \u00b1 5.0 mm Hg, with a mean pressure drop of 24.4 \u00b1 10.9 mm Hg (62%; p = 0.005). According to definition A, life-table analysis showed an overall success rate of 80%, while according to definition B, the success rate was 50% after 24 months of follow-up. Complications were infrequent and not serious. No complications resulting from the reticulated HA therapy itself were observed.",
            "output": [
                "Do pilot study of glaucoma drainage implant surgery supplemented with reticulated hyaluronic acid gel in severe glaucoma?"
            ]
        },
        {
            "id": "task847-4ee4dd993e2d4d18bc8a7da91aba9e41",
            "input": "Identify and compare phenotypic properties of osteoblasts from patients with otosclerosis (OSO), normal bones (HOB), and normal stapes (NSO) to determine a possible cause for OSO hypermineralization and assess any effects of the bisphosphonate, alendronate.', 'OSO (n = 11), NSO (n = 4), and HOB (n = 13) cultures were assayed for proliferation, adhesion, mineralization, and gene expression with and without 10(-10)M-10(-8)M alendronate.', 'Academic hospital.', 'Cultures were matched for age, sex, and passage number. Cell attachment and proliferation + alendronate were determined by Coulter counting cells and assaying tritiated thymidine uptake, respectively. At 7, 14, and 21 days of culture + alendronate, calcium content and gene expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were determined.', 'OSO had significantly more cells adhere but less proliferation than NSO or HOB. Calcification was significantly increased in OSO compared to HOB and NSO. NSO and HOB had similar cell adhesion and proliferation rates. A dose-dependent effect of alendronate on OSO adhesion, proliferation, and mineralization was found, resulting in levels equal to NSO and HOB. All cultures expressed osteoblast-specific genes such as RUNX2, alkaline phosphatase, type I collagen, and osteocalcin. However, osteopontin was dramatically reduced, 9.4-fold at 14 days, in OSO compared to NSO. Receptor activator of nuclear factor \u03baB ligand/osteoprotegerin (RANKL/OPG), important in bone resorption, was elevated in OSO with decreased levels of OPG levels. Alendronate had little effect on gene expression in HOB but in OSO increased osteopontin levels and decreased RANKL/OPG.",
            "output": [
                "Are differences in otosclerotic and normal human stapedial osteoblast properties normalized by alendronate in vitro?"
            ]
        },
        {
            "id": "task847-7ccea7c1e73d43d0ac6c77f9a0b45ccf",
            "input": "Kisspeptin and naloxone stimulate the reproductive axis while morphine inhibits its function. We have investigated the effect of central injection of kisspeptin-10 on mean plasma testosterone concentration in morphine or naloxone pretreated rats.', 'In this experimental study, 60 male Wistar rats that were divid- ed into 12 groups (n=5 per group) received saline, kisspeptin (1 nmol, ICV), naloxone (2 mg/kg, subcutaneously), morphine (5 or 10 mg/kg, sc) or co-administrations of kisspeptin, morphine and naloxone at 09:00 - 09:30. In the co-administrated groups, kisspeptin was injected 15 minutes following morphine or naloxone injections. Blood samples were collected 60 minutes following injections via the tail vein. Plasma testosterone concentration was measured by a rat testosterone ELISA kit.', 'Central injection of kisspeptin or subcutaneous injection of naloxone significantly increased the mean plasma testosterone concentration compared to saline while subcutaneous injections of different doses of morphine (5 or 10 mg/kg) significantly decreased testosterone compared to saline. The results revealed that morphine significantly attenuated the testosterone increase after kisspeptin injection compared to kisspeptin while a stimulatory additive effect was observed in the kisspeptin/naloxone group compared to either naloxone or kisspeptin.",
            "output": [
                "Does morphine attenuate testosterone response to central injection of kisspeptin in male rats?"
            ]
        },
        {
            "id": "task847-f134a091a6704ef48bb77cc6e8d00b19",
            "input": "Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development.', \"Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations.\", 'We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of \u22655ms was predicted with up to 79% sensitivity and 100% specificity.",
            "output": [
                "Does prediction of Thorough QT study result using action potential simulations based on ion channel screens?"
            ]
        },
        {
            "id": "task847-d41a8c263d134ecfa309ed30801d8836",
            "input": "Excess adipose tissue is a source of inflammation. Polycystic ovary syndrome (PCOS) is a proinflammatory state and is often associated with excess abdominal adiposity (AA) alone and/or frank obesity.', 'To determine the effect of glucose ingestion on cytokine release from mononuclear cells (MNC) in women with PCOS with and without excess AA and/or obesity.', 'A cross-sectional study.', 'Academic medical center.', 'Twenty-three women with PCOS (seven normal weight with normal AA, eight normal weight with excess AA, eight obese) and 24 ovulatory controls (eight normal weight with normal AA, eight normal weight with excess AA, eight obese).', 'Three-hour 75-g oral glucose tolerance test (OGTT).', 'Body composition was measured by dual energy x-ray absorptiometry. Insulin sensitivity was derived from the OGTT (ISOGTT). TNF\u03b1, IL-6, and IL-1\u03b2 release was measured in supernatants of cultured MNC isolated from blood samples drawn while fasting and 2 hours after glucose ingestion.', 'Insulin sensitivity was lower in obese subjects regardless of PCOS status and in normal-weight women with PCOS compared with normal-weight controls regardless of body composition status. In response to glucose ingestion, MNC-derived TNF\u03b1, IL-6, and IL-1\u03b2 release decreased in both normal-weight control groups but failed to suppress in either normal-weight PCOS group and in obese women regardless of PCOS status. For the combined groups, the cytokine responses were negatively correlated with insulin sensitivity and positively correlated with abdominal fat and androgens.",
            "output": [
                "Is the altered mononuclear cell-derived cytokine response to glucose ingestion regulated by excess adiposity in polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-9611bbcb1e82416ba189176cfcc64544",
            "input": "Surgical site infections (SSIs) after colectomy for colon cancer (CC), Crohn's disease (CD), and diverticulitis (DD) significantly impact both the immediate postoperative course and long-term disease-specific outcomes. We aim to profile the effect of diagnosis on SSI after segmental colectomy using the National Surgical Quality Improvement Program (NSQIP) data set.\", \"NSQIP data from 2006 to 2011 were investigated, and segmental colectomy procedures performed for the diagnoses of Crohn's disease, DD, and colon malignancy were included. SSI complications were compared by diagnosis using univariate and multivariate analysis.\", 'We included 35,557 colectomy cases in the analysis. CD had the highest rate of postoperative SSI (17 vs. 13% DD vs. 10% CC; p\\u2009<\\u20090.001). Using CC as the comparison group and controlling for multiple variables, the multivariate analysis showed that the CD group had an increased risk for acquiring at least one SSI (odds ratio (OR)\\u2009=\\u20091.38, p\\u2009\u2264\\u20090.001), deep incisional SSI (OR\\u2009=\\u20091.85, p\\u2009=\\u20090.03), and organ space SSI (OR\\u2009=\\u20091.51, p\\u2009=\\u20090.02).",
            "output": [
                "Is crohn 's disease but not diverticulitis an independent risk factor for surgical site infections in colectomy?"
            ]
        },
        {
            "id": "task847-e0ca3385b3464059936d702ea3e970bf",
            "input": "Dopamine and corticotrophin-releasing hormone (CRH; also known as corticotrophin-releasing factor) are key neurotransmitters in the interaction between stress and addiction. Repeated treatment with cocaine potentiates glutamatergic transmission in the rat basolateral amygdala/cortex pathway through a synergistic action of D1 -like dopamine receptors and CRH type-2\u03b1 receptors (CRF2 \u03b1 receptors). We hypothesized that this observed synergism could be instrumented by heteromers containing the dopamine D1 receptor and CRF2 \u03b1 receptor.', 'D1 /CRF2 \u03b1 receptor heteromerization was demonstrated in HEK293T cells using co-immunoprecipitation, BRET and FRET assays, and by using the heteromer mobilization strategy. The ability of D1 receptors to signal through calcium, when singly expressed or co-expressed with CRF2 \u03b1 receptors, was evaluated by the calcium mobilization assay.', 'D1 /CRF2 \u03b1 receptor heteromers were observed in HEK293T cells. When singly expressed, D1 receptors were mostly located at the cell surface whereas CRF2 \u03b1 receptors accumulated intracellularly. Interestingly, co-expression of both receptors promoted D1 receptor intracellular and CRF2 \u03b1 receptor cell surface targeting. The heteromerization of D1 /CRF2 \u03b1 receptors maintained the signalling through cAMP of both receptors but switched D1 receptor signalling properties, as the heteromeric D1 receptor was able to mobilize intracellular calcium upon stimulation with a D1 receptor agonist.",
            "output": [
                "Do dopamine D1 and corticotrophin-releasing hormone type-2\u03b1 receptors assemble into functionally interacting complexes in living cells?"
            ]
        },
        {
            "id": "task847-577753255b5c4da691b843f5d1e5b999",
            "input": "High sensitivity C-reactive protein (Hs-CRP) and adiponectin (APN) are two critical cytokines and exert inverse effects on atherosclerosis initiation and progression. The purpose of our study was to investigate the value of Hs-CRP and ANP ratio (Hs-CRP/APN ratio) on evaluating atherosclerosis progression.', \"One hundred sixty consecutive participants underwent carotid intima-media thickness (CIMT) measured by ultrasound were enrolled and drawn fasting blood samples for plasma levels Hs-CRP and APN, serum levels of lipid profiles and fasting blood glucose evaluation. Other anthropometrics and clinical status were collected by questionnaire. All participants were divided into 4 groups according to the baseline Hs-CRP/APN ratio and underwent CIMT measurement every 6 months. CIMT increment and composite cardiovascular endpoints were compared after 24 months' follow-up.\", \"At baseline, body mass index (BMI), smoking, diabetic mellitus, usage of statins, Hs-CRP and APN independently correlated with Hs-CRP/APN ratio as analyzed by spearman rank correlation. Smoking, serum level of LDL-C, plasma level of Hs-CRP and Hs-CRP/APN ratio were positively correlated with CIMT while usage of statins and plasma level of APN were negatively correlated with CIMT as analyzed by multiple linear regression analysis. After 24 months' follow-up, the progression of CIMT was the most prominent in the fourth quartile of baseline Hs-CRP/APN ratio. In addition, the incidence of composite cardiovascular endpoint was also higher in the fourth quartile as compared to the other 3 lower quartiles.",
            "output": [
                "Is increased Hs-CRP/adiponectin ratio associated with increase carotid intima-media thickness?"
            ]
        },
        {
            "id": "task847-824fb545720c4f3fa4051049c05dece4",
            "input": "To evaluate the usefulness of fluorescence in situ hybridization (FISH) on peripheral-blood specimens to evaluate the cytogenetic response to treatment in patients with chronic myeloid leukemia (CML).', 'In a first attempt, we analyzed 62 bone marrow specimens using interphase FISH and compared the results with those of conventional cytogenetics. In a second step, we analyzed 60 paired sets of bone marrow and peripheral-blood specimens with interphase FISH.', 'The results of interphase FISH agreed with conventional cytogenetics on bone marrow for most patients, and only minor differences were found (r =.98). The comparison of interphase FISH on bone marrow versus peripheral-blood specimens showed a strong correlation between these two specimen sources (r =.97).",
            "output": [
                "Is fluorescence in situ hybridization on peripheral-blood specimens a reliable method to evaluate cytogenetic response in chronic myeloid leukemia?"
            ]
        },
        {
            "id": "task847-0ff4b9bc0e4744ec8ec21491eeacd9a6",
            "input": "Development of antibodies and hypersensitivity to asparaginase are common and may attenuate asparaginase effect. Our aim was to determine the relationship between antiasparaginase antibodies or hypersensitivity reactions and event-free survival (EFS).', 'One hundred fifty-four children with acute lymphoblastic leukemia received Escherichia coli asparaginase 10,000 IU/m(2) intramuscularly three times weekly for nine doses during multiagent induction and reinduction phases and for seven monthly doses during continuation treatment. Erwinia asparaginase was used in case of clinical hypersensitivity to E coli but not for subclinical development of antibodies. Plasma antiasparaginase antibody concentrations were measured on day 29 of induction in 152 patients.', 'Antibodies were detectable in 54 patients (35.5%), of whom 30 (55.6%) exhibited hypersensitivity to asparaginase. Of the 98 patients who had no detectable antibodies, 18 (18.4%) had allergic reactions. Patients with antibodies were more likely to have a reaction than those without antibodies (P <.001). Among the 50 patients who experienced allergic reactions (including two for whom antibodies were not measured), 36 (72.0%) were subsequently given Erwinia asparaginase; seven (19.4%) reacted to this preparation. EFS did not differ among patients who did and did not have antibodies (P =.54), with 4-year EFS (+/- 1 SE) of 83% +/- 6% and 76% +/- 5%, respectively. Similarly, EFS did not differ among patients who did and did not develop allergic reactions (P =.68), with 4-year estimates of 82% +/- 6% and 78% +/- 5%, respectively.",
            "output": [
                "Does hypersensitivity or development of antibodies to asparaginase impact treatment outcome of childhood acute lymphoblastic leukemia?"
            ]
        },
        {
            "id": "task847-e7f64840cf854df890f4640a786d284b",
            "input": "To assess the safety and efficacy of vinorelbine in patients with AIDS-related Kaposi's sarcoma (KS).\", 'From December 1994 to May 1997, within the Italian Cooperative Group on AIDS and Tumors, we enrolled 36 patients with AIDS-related KS who experienced disease progression after one or more regimens of systemic chemotherapy. Patients were treated with vinorelbine 30 mg/m(2) every 2 weeks by intravenous bolus.', 'Of 35 assessable patients, three (9%) had a clinical complete response and 12 (34%) had a partial remission, for an overall objective response rate of 43% (95% confidence interval, 26% to 61%). For the 15 patients with objective responses, the median duration of response from the beginning of therapy until the development of progression was 176 days, whereas the median progression-free survival and the median survival durations for 35 assessable patients were 151 days and 216 days, respectively. Vinorelbine also induced responses in patients who had become resistant to regimens that included other vinca alkaloids. Overall, vinorelbine was well tolerated. Toxicity, including neurologic toxicity, was mild and reversible. Neutropenia was the most frequent dose-limiting toxicity.",
            "output": [
                "Is vinorelbine an effective and safe drug for AIDS-related Kaposi 's sarcoma : results of a phase II study?"
            ]
        },
        {
            "id": "task847-970134e43c2844a78dccb41bfd2b5b39",
            "input": "To determine whether testosterone levels change as women with the polycystic ovary syndrome (PCOS) grow older.', 'A follow-up cross-sectional study of a cohort of women with PCOS identified up to 20-25 years ago.', 'Women with PCOS were recruited primarily from practice records between 1970 and 1990. Voter registration tapes and household directories were used to identify age-, race-, and neighborhood-matched controls.', 'Eighty-four women with PCOS, 20-57 years of age, and 37 age-matched controls participating in a study of the risk for cardiovascular disease in women with PCOS.', 'Clinical data were collected by questionnaire and fasting blood samples were obtained randomly throughout the menstrual cycle.', 'Total and non-SHBG-bound testosterone levels.', 'Total and non-SHBG-bound testosterone levels were similar in women with PCOS who were 20-42 years of age but were reduced by approximately 50% among women 42-47 years of age and remained stable in women older than 47 years of age. Testosterone levels were increased in younger and older women with PCOS compared with controls but were similar to controls in women 42-47 years of age.",
            "output": [
                "Do serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-c97ccd12fdc447b695fdd97e41bca35d",
            "input": "To investigate the relationship between ovarian androgen excess and impaired growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in nonobese women with polycystic ovary syndrome (PCOS).', 'A prospective, controlled clinical study.', 'Reproductive Endocrine Unit, Department of Obstetrics and Gynecology, Jinling Hospital, Nanjing University School of Clinical Medicine.', 'Six patients with PCOS with both clomiphene resistance and gonadotropin hyperreponsiveness and six controls with regular cycles, matched for age and body mass index (BMI).', 'Bilateral ovarian wedge resection (OWR) was performed to induce ovulation surgically for these refractory women with PCOS. A GH stimulation test with oral L-dopa was arranged for controls and for patients with PCOS before and again 6 months later after OWR.', 'Plasma GH, IGF-1, FSH, LH, testosterone, androstenedione, estradiol, progesterone, prolactin, insulin, and glucose.', 'Basal levels and areas under the response curve of GH and GH-IGF-1 ratio to L-dopa were significantly lower in patients with PCOS before surgery than those of controls. The OWR in patients with PCOS obviously reduced their androstenedione and testosterone levels and insulin-glucose ratios, and increased the GH and GH-IGF-1 responses to L-dopa.",
            "output": [
                "Does androgen excess contribute to altered growth hormone/insulin-like growth factor-1 axis in nonobese women with polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-d1447153b861437093726412352f1564",
            "input": "We evaluated whether detecting prostate cancer cells by the nested reverse transcriptase-polymerase chain reaction (RT-PCR) in lymph nodes has predictive value for serum prostate specific antigen (PSA) recurrence in patients undergoing radical prostatectomy.', 'We assessed the presence of prostate cancer cells by RT-PCR for prostate specific membrane antigen and PSA assay in lymph nodes dissected from 38 patients with localized prostate cancer treated with radical prostatectomy. The results of nested RT-PCR assay were compared with biochemical recurrence.', 'Nested RT-PCR was positive in the lymph nodes of 2 of 18 patients (11%) with stage pT2a and 5 of 20 (25%) with stage pT2b disease. All 7 patients had biochemical recurrence. We noted a significant difference in the Kaplan-Meier recurrence-free actuarial probability curve in those with positive and negative nested RT-PCR results for prostate specific membrane antigen, PSA and prostate specific membrane antigen-PSA in the lymph nodes (p = 3.02x10(-7), 2.23x10(-7) and 3.02x10(-7), respectively). Multivariate analysis of serum PSA, Gleason score and preoperative RT-PCR assay in peripheral blood showed that nested RT-PCR for prostate specific membrane antigen, PSA and prostate specific membrane antigen-PSA in the lymph nodes were independent predictors of recurrence (p = 0.0089, 0.0075 and 0.0089, respectively).",
            "output": [
                "Is detection of micrometastatic prostate cancer cells in the lymph nodes by reverse transcriptase polymerase chain reaction predictive of biochemical recurrence in pathological stage T2 prostate cancer?"
            ]
        },
        {
            "id": "task847-fb91a77fd09a417aa2a14799c7258c1f",
            "input": "Uncontrolled clinical experience at our institution suggested that low-dose aprotinin could control excessive bleeding after cardiopulmonary bypass (CPB). A randomized clinical trial was conducted to determine the efficacy of low-dose aprotinin in the treatment of hemorrhage after cardiac surgery.', 'One hundred seventy-one patients undergoing cardiac surgery with CPB were included. Forty-four patients (26%) bled significantly in the intensive care unit (>100 mL/h) and received either aprotinin (200,000 KIU bolus + 100,000 KIU/h for 8 hours) or placebo in addition to our standard management of excessive bleeding.', 'Median bleeding before study drug administration was not different between aprotinin (200 mL) and placebo (212.5 mL) groups. Bleeding decreased significantly with time and similarly in both groups. Ninety-five percent of patients required transfusions in both groups. Median blood products transfused were 13 and 8 units per patient in the aprotinin and placebo groups respectively (p = NS).",
            "output": [
                "Is low-dose aprotinin ineffective to treat excessive bleeding after cardiopulmonary bypass?"
            ]
        },
        {
            "id": "task847-03e7e94edde04ae19d1d855be95b0ea2",
            "input": "Paraplegia can result from operations requiring transient occlusion of the thoracic aorta. A rat model of paraplegia with the characteristics of delayed paraplegia and transient ischemic dysfunction was developed to determine whether ischemic preconditioning (IPC) improved neurologic outcome.', 'Rats underwent balloon occlusion of the upper descending thoracic aorta. One group (2 minute IPC, n = 19) underwent 2 minutes of IPC and a second group (5 minute IPC, n = 19) had 5 minutes of IPC 48 hours before 10 minutes of occlusion. The control group (n = 31) had no IPC prior to 10 minutes of occlusion.', 'Paraplegia occurred in 68% of the control animals (21 of 31 paraplegic: 6 delayed and 15 immediate paraplegia). Both the 2-minute IPC and 5-minute IPC groups had a decreased incidence of paraplegia when compared to controls (32%, p = 0.011 and 26%, p = 0.009, respectively).",
            "output": [
                "Does ischemic preconditioning protect against paraplegia after transient aortic occlusion in the rat?"
            ]
        },
        {
            "id": "task847-8b4c520357084ee1b4a33f1cfa701ff3",
            "input": "To compare the postoperative analgesic effects of 50 mg diclofenac p.o. before surgery and intra-articular ropivacaine injected after diagnostic day-case knee arthroscopy performed under spinal anesthesia.', 'In a randomized, double-blind investigation, 200 ASA physical status 1-2 outpatients, age 18-60 yr, received either 50 mg diclofenac p.o. or placebo one hour before operation (100 patients per group), and intraarticular injections of either 20 ml of ropivacaine 0.5% or 20 ml of saline 0.9% (50 patients in each premedication groups). Patients received 50 mg diclofenac p.o. prn and, if needed, 0.1 mg x kg(-1) oxycodone im for postoperative pain relief. Patients were discharged home with a supply of 50 mg diclofenac tablets and were given a sheet of paper with knee pain VAS scales and a questionnaire of analgesics taken. Patients rated their VAS scores eight hours after surgery and in the moming and at the end of the first and the second postoperative days, respectively.', 'The only statistically significant difference was found when the diclofenac groups were combined and compared with the combined placebo premedication groups. The VAS scores of knee pain at eight hours after the operation were 19+/-22 in the two diclofenac premedication groups and 32+/-28 in the two placebo groups (P = 0.001).",
            "output": [
                "Does diclofenac premedication but not intra-articular ropivacaine alleviate pain following day-case knee arthroscopy?"
            ]
        },
        {
            "id": "task847-b8cbab2ff96d41359c62c65eb18dd5bf",
            "input": "To determine how anterior advancement of the mandible (ADM) affects spontaneous breathing through the nasal route in healthy human volunteers sedated with intravenous midazolam.', 'In four subjects who exhibited nasal breathing during midazolam sedation (intravenous dose: 0.09+/-0.02 mg x kg(-1), mean +/- SD), we measured respiratory rate (RR), peak nasal inspiratory airflow rate (V(nIpeak)) peak nasal expiratory airflow rate (V(nEpeak), duty ratio (Ti/Ttot) and nasal resistance (Rn) before and after ADM. Nasal resistance was calculated by dividing the difference between nasal mask and oropharyngeal pressure by airflow rate at peak nasal inspiratory airflow.', 'The RR, V(nIpeak), and V(nEpeak) increased following ADM (P<0.001, respectively). On the contrary, Ti/Ttot decreased after ADM (P<0.001). Consequently, ADM decreased Rn from 30.4+/-40.8 to 5.0+/-5.6 (cm H2O x l(-1) x sec(-1)) (mean +/- SD) (P<0.001). In these four subjects, no respiratory airflow was observed through the oral route before and after ADM.",
            "output": [
                "Does advancement of the mandible facilitate nasal breathing in human subjects sedated with midazolam?"
            ]
        },
        {
            "id": "task847-9c990c60290b4944a860bd1938756092",
            "input": "Angiotensin II stimulates vascular smooth muscle cell (VSMC) growth, and is considered to be an important mediator of intimal thickening after vascular injury. Recent evidence has indicated that VSMC apoptosis plays a major role in the response to balloon injury, and we therefore examined the effect of angiotensin converting enzyme (ACE)-inhibition on VSMC apoptosis and vascular lesion formation in the rat model of balloon injury.', 'Male Sprague-Dawley rats were subjected to carotid artery balloon injury and randomised to a standard diet or a diet supplemented with 1 mg/ml captopril in the drinking water. Animals were sacrificed 2 and 14 days after injury for assessment of apoptosis and proliferation by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) immunohistochemistry, respectively. At 14 days post injury, vessel cross-sections were subjected to microscopic morphometry and total cell numbers were determined.', 'At 2 days after balloon injury, captopril-treated animals displayed a significant increase in the percentage of TUNEL-positive VSMCs in the medial area (12 +/- 4% vs. 1 +/- 1%; P < 0.05) as compared to controls. This increase in early apoptosis was associated with decreased intimal cellularity 14 days post injury (238 +/- 47 cells/cross-section vs. 449 +/- 75 cells/cross-section; P < 0.05), and a reduction of neointimal formation (0.13 +/- 0.02 mm2 vs. 0.23 +/- 0.04 mm2; P < 0.05). The fraction of PCNA-positive VSMCs per cross-section 2 or 14 days after injury was not significantly altered by captopril administration.",
            "output": [
                "Does aCE-inhibition promote apoptosis after balloon injury of rat carotid arteries?"
            ]
        },
        {
            "id": "task847-ffad0aed2f3e4d108879ab9e9b1177f0",
            "input": "We sought to study the contribution of potassium channels in the effect of forskolin and 1,9-dideoxyforskolin on uterine contractility in the pregnant rat.', 'Rings taken from the middle portions of uterine horns from rats at 16 days of gestation were positioned in organ chambers containing physiologic salt solution bubbled with 5% carbon dioxide in air (37 degrees C, pH approximately 7.4) for isometric tension recording under 2 g passive tension. The effects of cumulative concentrations of forskolin and 1,9-dideoxyforskolin in the absence or presence of an adenylate cyclase inhibitor (MDL-12,330A, 10(-5) mol/L), a nonselective potassium channel blocker (tetrabutylammonium, 10(-4) mol/L), or an adenosine triphosphate-dependent potassium channel blocker (glibenclamide 10(-5) mol/L) were studied.', 'Both forskolin and, to a lesser extent, 1,9-dideoxyforskolin inhibit uterine contractions. Tetrabutylammonium, glibenclamide, and MDL-12, 330A attenuated the effects of forskolin, whereas glibenclamide was less effective against 1,9-dideoxyforskolin.",
            "output": [
                "Are adenylate cyclase and potassium channels involved in forskolin- and 1,9-dideoxyforskolin-induced inhibition of pregnant rat uterus contractility?"
            ]
        },
        {
            "id": "task847-498d8f802cbb44b0bc2970f8a0a0550f",
            "input": "Bacillary angiomatosis is a rare pseudoneoplastic angioproliferative lesion occurring in patients with AIDS. This condition has been associated with Bartonella henselae and Bartonella quintana infections. Human herpesvirus 8 (HHV-8) is thought to be the causative agent of Kaposi's sarcoma, a vasoproliferative neoplasm, also commonly found in patients with AIDS. The presence of HHV-8 in a cohort of patients with bacillary angiomatosis was investigated.\", 'Eight cutaneous cases of biopsy confirmed bacillary angiomatosis were assessed for HHV-8 using standard solution phase polymerase chain reaction (PCR).', 'No case of bacillary angiomatosis harboured HHV-8 DNA.",
            "output": [
                "Is hHV-8 ( KSHV ) associated with bacillary angiomatosis?"
            ]
        },
        {
            "id": "task847-daf5fbfe171145fe94d843d067ee1552",
            "input": "We investigated the combined effect of tissue plasminogen activator and ischemia on middle cerebral artery (MCA) reactivity to determine whether abnormal MCA function after 2 hours of ischemia was worse in arteries perfused with recombinant tissue plasminogen activator (rtPA).', 'The intraluminal suture model of focal cerebral ischemia was used to induce 2 hours of ischemia in rats, after which occluded MCAs were removed and studied in vitro with an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter. Arteries were either nonischemic (control; n=8), nonischemic and perfused with 400 microg/mL rtPA (rtPA; n=5), ischemic (ISC; n=6), or ischemic and perfused with 400 microg/mL rtPA (ISC-rtPA; n=6). After a 1-hour equilibration at 75 mm Hg, TMP was increased to 125 mm Hg and lumen diameter was recorded at each pressure. Reactivity to acetylcholine (ACh, 0.1 to 10.0 micromol/L) and serotonin (0.01 to 10 micromol/L) was then determined.', 'Control arteries responded myogenically to pressure and increased the amount of tone from 18.5+/-3.8% at 75 mm Hg to 24.8+/-3.0% at 125 mm Hg (P<0.05), which decreased diameter from 241+/-7 to 232+/-6 microm. In contrast, all other groups decreased tone at 125 mm Hg, which demonstrated a loss of myogenicity. The percent tone in each group at 75 versus 125 mm Hg was rtPA, 16.0+/-4.5% versus 11.8+/-3.8%; ISC, 23.5+/-4.5% versus 13. 5+/-3.1%; and ISC-rtPA, 23.5+/-4.2% versus 12.3+/-3.2% (P<0.05 for all). The percent increase in lumen diameter at each concentration of ACh was diminished in all groups compared with control; ISC-rtPA arteries responded the least, which suggests an additive effect of rtPA in ischemic arteries. The percent increase in lumen diameter at 10(-5)mol/L ACh was 23+/-4% for control versus 15+/-2% for rtPA; 17+/-3% for ISC arteries (P<0.05), and 8+/-2% for ISC-rtPA arteries (P<0.01). Sensitivity to serotonin was equally diminished in all groups compared with control: EC(50) (micromol/L) was 0.06+/-0.01 for control, 0.17+/-0.02 for rtPA, 0.22+/-0.07 for ISC, and 0.16+/-0. 04 for ISC-rtPA (P<0.05).",
            "output": [
                "Is postischemic attenuation of cerebral artery reactivity increased in the presence of tissue plasminogen activator?"
            ]
        },
        {
            "id": "task847-7bb6157919a74226844a4ccab2914845",
            "input": "Bronchopulmonary carcinoid tumors can be divided into typical and atypical carcinoids according to their histologic and clinical features. Atypical carcinoids tend to have less predictable biologic behavior and are associated with a worse prognosis than typical carcinoids. The authors examined apoptosis and the expression of apoptosis regulating proteins Bcl-2, Bax, Bak, and Mcl-1 in 21 typical and 10 atypical bronchopulmonary carcinoid tumors. To find features distinguishing the growth of these types of tumors, the expression of p53 protein and the proliferation marker Ki-67 were also investigated. Finally, the parameters were compared with clinical follow-up data.', \"Thirty-one bronchopulmonary carcinoid tumors were examined by using in situ 3'-end labeling of DNA (TUNEL) for apoptosis and immunohistochemical staining methods for Bcl-2, Bax, Bak, Mcl-1, p53, and Ki-67 in formalin fixed, paraffin embedded tissue specimens.\", 'The apoptotic indices (AIs) were low in general (mean 0.18%), but higher AIs (> 0.5%) were observed significantly more often in atypical than in typical carcinoids (P < 0.008) in association with shortened survival (P < 0. 008). No relation between apoptosis and Bcl-2, Bax, Bak, or Mcl-1 expression was found. Expression of p53 protein was detected in only three atypical carcinoids, which also had significantly higher AIs than p53 negative tumors (P < 0.03). Proliferation rates measured by Ki-67 index were unusually low; the highest proliferation rates were observed in atypical carcinoids. There was a positive correlation between AI and Ki-67 indices (P < 0.01).",
            "output": [
                "Do atypical bronchopulmonary carcinoids show a tendency toward increased apoptotic and proliferative activity?"
            ]
        },
        {
            "id": "task847-31853ba25e114c4698872e8636c9b8a0",
            "input": "Terlipressin decreases portal pressure. However, its effects on variceal pressure have been poorly investigated. This study investigated the variceal, splanchnic and systemic hemodynamic effects of terlipressin.', 'Twenty cirrhotic patients with esophageal varices grade II-III, and portal pressure > or =12 mmHg were studied. Hepatic venous pressure gradient, variceal pressure and systemic hemodynamic parameters were obtained. After baseline measurements, in a double-blind administration, 14 patients received a 2mg/iv injection of terlipressin and six patients received placebo. The same measurements were repeated 60 min later.', 'No demographic or biochemical differences were observed in basal condition between groups. Terlipressin produced significant decreases in intravariceal pressure from 20.9+4.9 to 16.3+/-4.7 mmHg (p<0.01, -21+/- 16%), variceal pressure gradient from 18.9+/-4.8 to 13.5+/-6.0 mmHg (p<0.01, -28+/-27%), estimated variceal wall tension from 78+/-29 to 59+/-31 mmHg x mm (p<0.01, -27+/-22%), and hepatic venous pressure gradient from 19.4+/-4.5 to 16.8+/-5 mmHg (p<0.01, -14+/-12%) at 60 min. The change in variceal pressure after 60 min of terlipressin administration was greater than the change in wedge hepatic venous pressure (-4.7 mmHg vs -0.5 mmHg, respectively, p<0.0001). Terlipressin also caused significant decreases in heart rate and cardiac index and increases in mean arterial pressure and peripheral vascular resistance.",
            "output": [
                "Is terlipressin more effective in decreasing variceal pressure than portal pressure in cirrhotic patients?"
            ]
        },
        {
            "id": "task847-97cd6817ebb74603a2d1b8e88551350d",
            "input": "This study investigated whether hyperbaric oxygen therapy (HBOT) improves recovery after exercise-induced muscle injury.', 'Healthy male subjects (N = 24) were randomly assigned to either a placebo group or a HBOT group. Subjects were tested for maximal isometric strength (preexercise) of their right elbow flexors. Each subject then completed a high-force eccentric workout of the elbow flexor muscle group to induce delayed onset muscle soreness (DOMS). On the seven successive days after this workout, the subjects were exposed to a hyperbaric environment of 2.5 ATA for 60 min, inspiring either a normoxic mixture (P(I)O2 = 0.2 ATA; placebo group) or a hyperoxic gas mixture (P(I)O2 = 2.5 ATA; HBOT group). Before the eccentric workout and daily for the next 10 d, measurements were obtained regarding: maximal isometric muscle strength of the elbow flexor muscles, right upper arm circumferences, and rating of the perceived muscle soreness.', 'Isometric strength decreased significantly from preexercise levels of 25.1 +/- 3.8 kp to postexercise levels of 12.0 +/- 4.6 kp, for the HBOT group, and from 24.6 +/- 3.4 kp to 12.5 +/- 3.7 kp, respectively, for the placebo group. Over the 10-d recovery period, there was no difference in the rate of recovery of muscle strength between the two groups. Perceived soreness peaked at about 48 h after exercise with no difference between groups. Also, the exercise-induced increases in arm circumference were similar in the two groups.",
            "output": [
                "Does hyperbaric oxygen therapy affect recovery from delayed onset muscle soreness?"
            ]
        },
        {
            "id": "task847-bef15298ee0e4925acaca4a430969f79",
            "input": "Lung inflation causes cardiovascular suppression via an increase in intrathoracic pressure and neural mechanisms. To examine the mechanisms involved, we mea-sured the heart rate (HR) and arterial blood pressure (AP) responses to lung inflation before and after spraying the bronchi with lidocaine to suppress airway reflex. Thirty women participated in the study. One group (n = 20, Group BT) had their tracheas intubated by using double-lumen tubes. The other group (n = 10, Group TT) received an ordinary endotracheal tube. They were all studied under general anesthesia by using nitrous oxide, isoflurane, and muscle relaxation after a thiopental induction. In each patient, airway pressure was increased for 3 s, and changes in HR and AP were measured. Lung inflation was repeated after 5 mL of 4% lidocaine had been sprayed into the main bronchi unilaterally in Group BT or bilaterally in Group TT. There were no significant differences in cardiovascular responses between left and right lung inflation with the pressure at 20 and 30 cm H(2)O. Both lungs inflated at 20 cm H(2)O caused an increase in HR with a significantly greater decrease in AP than with unilateral inflation. Anesthesia of the bronchi abolished the HR increase, but not the AP decrease. Lung inflation at 30 cm H(2)O caused significant decreases in HR and AP which were not affected with topical anesthesia. These results indicate that the cardiovascular responses elicited by lung inflation in anesthetized humans are predominantly the direct effect of the increase in intrathoracic pressure, although sympathetic afferent activity induced via stimulation of mechanoreceptors in the airways contributes.",
            "output": [
                "Does localized airway anesthesia with lidocaine partially suppress cardiovascular responses To lung inflation?"
            ]
        },
        {
            "id": "task847-a726aa5b25f6474688d1f124283fd9cd",
            "input": "A somatoanal reflex had been demonstrated in our previous work. Because nitric oxide plays an important role in mediating relaxation of the internal anal sphincter, our purpose was to examine whether and how local somatothermal stimulation inhibits the function of the internal anal sphincter by stimulating nitric oxide release via nitrergic neurons and to elucidate the possible mechanism.', 'The activity of the internal anal sphincter in anesthetized rabbits was measured by use of continuously perfused, open-tip manometric methods. Local somatothermal stimulation was achieved by applying an electroheating rod 1 cm away from the skin area at the right popliteal region. The responses were further manipulated by pre-treating the rabbits with agonists or antagonists linked to nitric oxide synthesis.', 'The motility of the internal anal sphincter before and during local somatothermal stimulation was significantly different (tonic pressure (mean +/-standard error of the mean), 5.4 +/- 0.3 vs. 4.9 +/- 0.3 mmHg, P = 0.0195; phasic pressure, 3.9 +/- 0.6 vs. 2.9 +/- 0.4 mmHg, P = 0.0002; frequency distribution of the phasic contractions (peak-to-peak interval), 28.9 +/- 3.7 vs. 65.3 +/- 10.4 seconds, P = 0.0001). The response began at approximately one minute after local somatothermal stimulation when the skin temperature was 41 +/- 0.3 degrees C. No anal response was observed when local somatothermal stimulation was applied at the control area. The local somatothermal stimulation-induced internal anal sphincter relaxation was not inhibited by pretreatment with atropine, propranolol, or phentolamine (tonic pressure, 5.8 +/- 1 vs. 5.2 +/- 0.8 mmHg, P = 0.038; phasic pressure, 4.2 +/- 0.9 vs. 3.1 +/- 0.6 mmHg, P = 0.020; peak-to-peak interval, 27.2 +/- 4.3 vs. 52.9 +/- 14.5 seconds, P = 0.043) but was completely blocked by pretreatment with a nitric oxide synthesis inhibitor. The effect of the nitric oxide synthesis inhibitor could be reversed by pretreatment with L-arginine (tonic pressure, 6 +/- 0.7 vs. 5.6 +/- 0.7 mmHg, P = 0.047; phasic pressure, 4.7 +/- 0.7 vs. 3.9 +/- 0.5 mmHg, P = 0.048; peak-to-peak interval, 23.8 +/- 3 vs. 33 +/- 3.7 seconds, P = 0.048), but not by D-arginine.",
            "output": [
                "Does local somatothermal stimulation inhibit motility of the internal anal sphincter through nitrergic neural release of nitric oxide?"
            ]
        },
        {
            "id": "task847-571f5844d15d4ef0903e3f1e720dde3c",
            "input": "Soluble silica, a ubiquitous component of the diet, may be the natural ligand for dietary aluminum and may prevent its accumulation and toxicity in animals. However, previous studies on the inhibition of aluminum absorption and toxicity by soluble silica have produced conflicting results. We recently identified a soluble silica polymer, oligomeric silica, that has a much higher affinity for aluminum than does monomeric silica and that may be involved in the sequestration of aluminum.', 'By using (26)Al as a tracer, we investigated the effects of oligomeric and monomeric silica on the bioavailability of aluminum (study 1) and compared the availability of silicon from oligomeric and monomeric silica in the human gastrointestinal tract (study 2).', 'In study 1, three healthy volunteers each ingested aluminum alone (control), aluminum with oligomeric silica (17 mg), and aluminum with monomeric silica (17 mg). In study 2, five healthy volunteers ingested both the oligomeric and monomeric forms of silica (34 mg). Serum and urine samples were analyzed for aluminum and silicon.', 'Oligomeric silica reduced the availability of aluminum by 67% (P = 0.01) compared with the control, whereas monomeric silica had no effect (P = 0.40). Monomeric silica was readily taken up from the gastrointestinal tract and then excreted in urine (53%), whereas oligomeric silica was not detectably absorbed or excreted.",
            "output": [
                "Does oligomeric but not monomeric silica prevent aluminum absorption in humans?"
            ]
        },
        {
            "id": "task847-f0933aaf77b849d68db7a8b8842d9557",
            "input": "Recent studies have implicated intracellular transduction pathways and neurotrophic factors in the action of antidepressants. Adaptation in these pathways may ultimately affect electrophysiological and morphological properties of neurones. We have previously shown that repeated electroconvulsive stimulation, a safe and effective antidepressant treatment, has profound effects on hippocampal synaptic connectivity and plasticity in the rat. Here, we investigated whether these electrophysiological properties were shared by the chemical antidepressant, fluoxetine.', 'To compare the electrophysiological and cognitive effects of two very different antidepressant treatments: repeated electroconvulsive stimulation (rECS); and chronic administration of the serotonin specific re-uptake inhibitor (SSRI), fluoxetine.', 'Rats were exposed to either rECS or daily fluoxetine administration for 15 days. The animals were then anaesthetised and dentate field excitatory post-synaptic potential (fEPSP) characteristics were measured before and after the induction of long-term potentiation (LTP) by high frequency perforant path stimulation. In a separate experiment, the effects of rECS and chronic fluoxetine administration on acquisition and retention of a spatial learning task in the Morris watermaze were determined.', 'Chronic fluoxetine administration and rECS produced equivalent increases in dentate fEPSP compared to respective control groups. LTP induction was attenuated in both groups. Spatial learning was, in contrast, unaffected by fluoxetine treatment but significantly impaired following rECS.",
            "output": [
                "Do repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity?"
            ]
        },
        {
            "id": "task847-d4154fae5a964bfbaff80ac4b02a352f",
            "input": "We quantitatively evaluated the collagen-to-smooth muscle tissue matrix ratio in ureteropelvic junction obstruction, and compared the ratio with the degree of obstruction, patient age and postoperative renal recovery.', \"We analyzed histological sections from 65 patients with ureteropelvic junction obstruction and 6 normal controls. Morphological and functional grading systems were adapted to determine the degree of renal obstruction. To examine smooth muscle and collagen tissue, sections were stained using Masson's trichrome. Two distinct populations of collagen versus smooth muscle were identified and the tissue matrix ratio was calculated by color image analysis.\", 'The mean tissue matrix ratio plus or minus standard deviation was 1.32+/-0.79 in all patients with ureteropelvic junction obstruction but only 0.30+/-0.10 in normal controls (p <0.0001). It appeared that the lower the tissue matrix ratio, the better the improvement in postoperative hydronephrosis (r = -0.50, p = 0.0001). Better recovery of renal function after pyeloplasty was observed with a decrease in the tissue matrix ratio (r = -0.43, p = 0.0004). We divided patients according to the tissue matrix ratio into groups 1--ratio 1 or less, 2--greater than 1 to 1.5 and 3--greater than 1.5 to determine a more detailed and clinically applicable correlation of tissue matrix ratio with postoperative renal functional changes. Better improvement in postoperative renal function was observed in group 1 than in group 3 (p = 0.002). Also, the tissue matrix ratio increased with patient age (r = 0.33, p = 0.007).",
            "output": [
                "Does collagen-to-smooth muscle ratio help prediction of prognosis after pyeloplasty?"
            ]
        },
        {
            "id": "task847-5356025ae741490eb1da00bcae6e7ac7",
            "input": "Impaired insulin sensitivity has been linked with chronic heart failure (CHF). Exercise has a beneficial effect on insulin sensitivity in healthy subjects. It is used also as an adjunctive therapy in patients with CHF. We studied the effect of randomized treatment with celiprolol, a vasodilating beta(1)-adrenoceptor antagonist, 200 mg once daily (n=20) or placebo (n=11) on serum lipid levels and insulin sensitivity in patients with CHF. In addition, all subjects participated in a 6-month exercise training protocol. Thirteen subjects in the celiprolol and eight subjects in the control group were on additional beta(1)-adrenoceptor antagonist as part of their tailored CHF therapy. Insulin sensitivity was determined using the hyperinsulinemic euglycemic clamp test (diabetic subjects excluded, n=11 for the celiprolol group and n=8 for the placebo group).', 'Insulin sensitivity index (ISI) increased by 33% (P<0.05) in the celiprolol group and by 17% (NS) in the control group. The mean increase in the whole group was 20% [from 68.2+/-11.5 to 81.7+/-10.7 ml/min/kg (mU/l), P<0.05]. No change was found in the total cholesterol level. HDL cholesterol levels increased by 12% (from 0.98+/-0.05 to 1.10+/-0.05 mmol/l, P<0. 005), and HDL/total cholesterol and HDL/LDL cholesterol ratios by 15% and 16%, respectively (P<0.005). The increase in serum fasting HDL cholesterol level was greater in the celiprolol-treated group (P<0.05). At baseline ISI correlated with maximal oxygen uptake (r=0. 65, P<0.0001) and body mass index (r=-0.55, P<0.001). The change in ISI correlated weakly with the improvement in muscle exercise capacity (r=0.53, P<0.05).",
            "output": [
                "Does celiprolol augment the effect of physical exercise on insulin sensitivity and serum lipid levels in chronic heart failure?"
            ]
        },
        {
            "id": "task847-594c9afba05d440c9986bf59ff204f9a",
            "input": "To identify in the adult and developing rodent eye cells expressing the gene encoding plasminogen activator inhibitor-1 (PAI-1), an important component of the fibrinolytic system.', 'PAI-1 mRNA was localized in cryostat thin eye sections via in situ hybridization analysis using specific 35S-labeled riboprobes. PAI-1 activity was tested in the aqueous humor using one-phase reverse zymography.', 'In the adult eye, PAI-1 mRNA was detected exclusively in epithelial cells of the ciliary processes, primarily in the apexes. In addition, PAI-1 activity was detected in the aqueous humor. PAI-1 mRNA was first found in the ciliary epithelium in embryonic day 18.5, when the ciliary body has reached an advanced developmental stage. PAI-1 mRNA was also detected in the ganglion cell layer of the retina at postnatal days 1 to 4, when angiogenesis takes place.",
            "output": [
                "Is plasminogen activator inhibitor-1 mRNA localized in the ciliary epithelium of the rodent eye?"
            ]
        },
        {
            "id": "task847-453a83a58437428fbd6b5d029c74d762",
            "input": "To determine whether cholestanol induces cornea endothelial and lens epithelial cell death in vitro.', 'Cornea endothelial and lens epithelial cells were cultured in minimum essential media with 10% fetal bovine serum containing 10 microg/ml cholesterol in ethanol, 10 microg/ml cholestanol in ethanol, or 1% ethanol. These cells, stained using the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) method, were analyzed by laser cytometer. The activities of ICE and CPP32 proteases in cells were also measured.', 'Both cornea endothelial and lens epithelial cells cultured with 10 microg/ml cholestanol showed a significant loss of viability. The nuclei of these cells cultured with 10 microg/ml cholestanol were more frequently stained than those exposed to 10 microg/ml cholesterol or 1% ethanol. Quantitative analysis of apoptotic DNA fragmentation confirmed that the cholestanol induced apoptosis of these cells in a time-dependent manner. The activities of interleukin-1beta-converting enzyme (ICE) and CPP32 proteases for cells cultured with 10 microg/ml cholestanol were significantly higher than those observed in control cells.",
            "output": [
                "Does cholestanol induce apoptosis of corneal endothelial and lens epithelial cells?"
            ]
        },
        {
            "id": "task847-fd60fc1d96494722adaaa80aa2828896",
            "input": "To examine the effect of human conjunctival fibroblasts on the survival and functional activity of human peripheral blood eosinophils.', 'Eosinophils were purified by negative immunoselection [magnetic activated cell sorter (MACS), purity > 97%] from volunteers with mild atopia. Fibroblasts were cultured from conjunctival specimens of healthy donors. Eosinophils were cultured on confluent monolayers of conjunctival fibroblasts or in culture medium alone. Eosinophil survival was evaluated by the trypan blue exclusion test. Eosinophil adherence was assessed by counting the attached cells after washing the cultures. Eosinophil viability and adherence in coculture were also assessed in the presence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF), anti-interleukin (IL)-3, and anti-IL-5 neutralizing antibodies. Cocultured eosinophils were activated by lipopolysaccharide (LPS) after 4 days in culture, and eosinophil peroxidase (EPO) release was determined as a marker of their activation.', 'Eosinophils cocultured with conjunctival fibroblasts had a significantly increased viability of 35.9% (P = 0.004) and 12.8% (P = 0.003) on days 4 and 8, respectively. Fibroblast-conditioned medium did not enhance the survival of eosinophils. The increase in eosinophil survival in coculture was partially inhibited by anti-GM-CSF (P = 0.019), anti-IL-3 (P = 0.033), or anti-IL-5 (P = 0.011), whereas eosinophil adherence was reduced by anti-GM-CSF alone (P = 0.034). LPS activation of eosinophils cultured for 4 days with conjunctival fibroblasts induced higher EPO release than in freshly isolated eosinophils (P = 0.01).",
            "output": [
                "Do conjunctival fibroblasts enhance the survival and functional activity of peripheral blood eosinophils in vitro?"
            ]
        },
        {
            "id": "task847-31a7f4cb63e944e0b24c3886b2865d0b",
            "input": "To determine the efficacy of screening women under age 50 with a significant family history of breast cancer.', 'Results from 22 Breast Units in the UK identified as being able to provide data were surveyed and pooled through regional data managers or consultant breast specialists.', 'Data relating to 8783 women screened and 9075 woman years of follow-up was analysed. Cancer incidence was 11.3/1000/year. The rate of cancer detection was 4. 78/1000 at prevalent screening and 4.52/1000 at incident screening. Median age at diagnosis was 43 years. Interval cancers presented at a rate of 2.45/1000. Comparison with the National Health Service Breast Screening Programme for women aged 50-64 revealed a similar rate of cancer detection and a similar incidence of ductal carcinoma in situ. The pathological features of screen-detected cancers in this study strongly suggest that prognosis for these women is more favourable than if they had presented symptomatically.",
            "output": [
                "Does screening women with a family history of breast cancer -- result from the British Familial Breast Cancer Group?"
            ]
        },
        {
            "id": "task847-db7a0cf72fea41ce9cb27a02c0421b46",
            "input": "Methotrexate has been steroid sparing for some patients with chronic sarcoidosis. We wished to determine whether methotrexate can be steroid sparing in the first year of corticosteroid therapy in sarcoidosis.', 'Patients with new onset, symptomatic disease within four weeks of starting on prednisone were randomized to receive either methotrexate or placebo for the next year. They were seen monthly and prednisone dosage was tapered following a pre-determined schedule.', 'Of 24 patients enrolled, only 15 received at least six months of therapy. Since methotrexate appears to take six months to be effective, only patients who completed six or more months of therapy were evaluated. The amount of prednisone per day decreased for both groups: methotrexate (First 6 months: Median 26 (Range 15-37) mg/day); Second 6 months 8 (1-22) mg/day, p < 0.01) and placebo (First 6 Months 28 (24-33) mg/day; Second 6 months 16 (11-22) mg/day, p < 0.02), with less prednisone used for the methotrexate patients versus placebo in the last six months (p < 0.01). There was also less weight gain for those patients receiving methotrexate. There was no difference in toxicity between methotrexate and placebo. The difference between methotrexate versus placebo was not seen when all patients (including the dropouts) were analyzed.",
            "output": [
                "Is methotrexate steroid sparing in acute sarcoidosis : results of a double blind , randomized trial?"
            ]
        },
        {
            "id": "task847-cd679eaf286c4c75913d6499e17ae854",
            "input": "To determine if the application of a continuous electrode paste band on precordial leads results in alteration of the electrocardiographic tracing as compared with an adequate amount of electrode paste, and if the former condition does not cause uniform morphologies from V1 to V6.', 'The amplitude and morphology of the electrocardiographic waves on the precordial leads in electrocardiographic tracings, which were performed with standard (control group) or excessive (continuous band) application of the electrode paste, were compared.', \"None of the 106 patients studied showed uniformity of the QRS morphology from V1 to V6. The electrocardiographic alterations identified in the tracings performed with a continuous electrode paste band that showed statistical significance in relation to the control group were the following: inversion of the P wave in V1; inversion of the T wave in V1, V2, and V3; appearance of R' waves in V1 and V2; disappearance of S waves in V1; appearance of S waves in V5 and V6; alterations in the amplitude of almost all waves, in all leads.",
            "output": [
                "Do analysis of the effects of the continuous electrode paste band on precordial leads of the electrocardiogram?"
            ]
        },
        {
            "id": "task847-d69a558f53a84b0c910bea68e6412700",
            "input": "Vascular endothelial growth factor (VEGF) is a hypoxia-induced endothelial cell-specific mitogen, which is angiogenic in vivo and up-regulated in several malignancies. VEGF can be used as a prognostic marker, but the effect of surgical trauma on serum VEGF (S-VEGF) concentrations is unknown and might reduce the value of VEGF as a serum marker.', 'We monitored S-VEGF levels by enzyme-linked immunosorbent assay in patients undergoing surgery.', 'Eighteen patients with major surgery had slightly elevated S-VEGF compared with the preoperative level (median 9.5 pg/mL) on the first (median 35 pg/mL; P = 0.0002) and third (median 19 pg/mL; P = 0.004) postoperative day, but not in later samples. The levels measured in 8 patients after minor surgery did not differ from the preoperative levels (P = 0.14).",
            "output": [
                "Does major surgery increase serum levels of vascular endothelial growth factor only temporarily?"
            ]
        },
        {
            "id": "task847-183b51c134b7438fa800c15332d81367",
            "input": "Lactoferrin supplementation suppresses ultraviolet light B (UV-B)-induced oxidation of cultures of human corneal epithelial cells. To investigate the protective effect of lactoferrin containing eyedrops against UV-B-induced corneal damage in vivo, we examined lactoferrin efficacy in a rat UV-B keratitis model.', 'Sprague-Dawley rats were irradiated with >10 kJ/m2 after anesthetization, and then corneal epithelial defect was observed at 24 h postirradiation. The pre- or postapplication of vehicle or lactoferrin-containing eyedrops was performed, and then corneal epithelial damage was scored based on fluorescein staining.', 'Posttreatment with lactoferrin did not inhibit the extent of corneal damage and did not affect wound healing. However, pretreatment by topical application of lactoferrin suppressed development of a corneal epithelial defect induced by UV-B irradiation in rats.",
            "output": [
                "Does lactoferrin protect against UV-B irradiation-induced corneal epithelial damage in rats?"
            ]
        },
        {
            "id": "task847-c80e748efdfc483d8e72e0e403846a6a",
            "input": "To evaluate the clinical significance of preoperative serum levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) in patients with resectable hepatocellular carcinoma (HCC).', 'IL-10 is an immunosuppressive factor and IL-6 is a multifunctional cytokine that plays a role in host defense mechanisms. Both have been reported to be related to the disease prognosis in some human solid tumors. Their role in human HCC has not been investigated.', 'Preoperative serum samples of 67 patients with HCC who underwent potentially curative resection and 27 normal healthy donors were assayed. Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay. The clinical significance of serum IL-10 and IL-6 was evaluated and compared with conventional clinicopathologic factors.', 'Levels of IL-10 and IL-6 were significantly higher in patients with HCC than in healthy subjects. There was no correlation between IL-10 and IL-6 levels. Tumor resection resulted in a decrease in IL-10 and IL-6 levels. On univariate analysis, patients with high IL-10 levels had a worse disease-free survival, but IL-6 levels had no correlation with the disease-free survival. Multivariate analysis identified IL-10 levels as a predictor of postresectional outcome, in addition to the well-established clinical risk factors.",
            "output": [
                "Is serum interleukin-10 but not interleukin-6 related to clinical outcome in patients with resectable hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-ce0073c93f6346759bc51aa8cf3d9645",
            "input": "Recently, several reports have described the ability of recombinant baculoviruses to transduce a variety of mammalian cells. Yet, mechanisms involved in baculovirus entry in those cells remain largely unexplored, particularly at the primary binding step of the virions to the cell membrane.', 'This report focused on the primary virus-cell interactions that lead to in vitro transduction of human 293 cells using a polyhedrin-deleted baculovirus harboring a CMV-driven beta-galactosidase gene (BacLacZ).', 'Infection rate monitored for 8 h and transduction rate with a multiplicity of infection of up to 800 were, both, non-saturable. Temperatures from 37 degrees C to 4 degrees C dramatically impaired BacLacZ but not adenovirus cell attachment. Competitive infections performed with an excess of a non LacZ-expressing baculovirus hardly competed at a 1/1 ratio. Consistent with an adsorptive binding process onto the cell surface, interactions through electrostatic charges between both viral and cell membranes appeared to be critical for BacLacZ transduction. The addition of polybrene to the cells prior to or during the infection prevented both virus binding and LacZ gene transfer, suggesting the involvement of negatively charged epitopes exposed at the cell surface. The simultaneous presence of the highly charged heparin abrogated BacLacZ binding to the cell surface and subsequent gene transfer. Lastly, direct in vitro binding of BacLacZ to heparin but not BSA columns could be demonstrated after elution of infectious BacLacZ virus in high salt molarity.",
            "output": [
                "Does baculovirus vector require electrostatic interactions including heparan sulfate for efficient gene transfer in mammalian cells?"
            ]
        },
        {
            "id": "task847-14b4085f541d4a0f90bfe02e2d8d6bab",
            "input": "Macrophages seem to play an important role in the development of glomerulosclerosis. In both human and experimental animal models of focal glomerulosclerosis (FSGS), infiltration of macrophages in the mesangium has been considered key in the development of FSGS.', \"In the present study, we evaluated the effect of vasoactive agents on the migration of monocytes across a filter in a modified Boyden chamber as well as across a cultured glomerular endothelial cell layer (in vitro model of glomerular mesangium). Both light as well as scanning electron microscopic studies were performed. We evaluated the effect of vasoactive agents including histamine, prostaglandin (PG) E2, angiotensin II, endothelin-1, platelet-activating factor, and interleukin-1 (IL) on the migration of monocytes/macrophages across an endothelial cell layer as well as a gelatin-coated filter. In addition, we evaluated the effect of cyclic adenosine 3',5' cyclic monophosphate (cAMP) and PGE2 on vasoactive-induced migration of monocytes.\", 'Histamine increased (P < 0.003) the migration of monocytes across the filter. This effect of histamine was dose-dependent. Histamine at concentrations of 10(-8) to 10(-5) mol/L induced optimal migration across the filter (control, 16.6 +/- 1.1 vs histamine, 10(-8) mol/L, 40.9 +/- 0.9 monocytes/high power field). Cimetidine, an H2 receptor blocker, attenuated (P < 0.001) the effect of histamine on the migration of monocytes. PGE2 inhibited the migration of monocytes in a dose-dependent manner. Histamine increased (P < 0.001) the passage of monocytes across the glomerular endothelial cell layer (control, 1012 +/- 37 vs 1711 +/- 163 cpm/well). Histamine also increased the migration of murine macrophages across the glomerular endothelial cell layer. PGE2 inhibited the migration of monocytes across the endothelial cell layer under basal as well as histamine-stimulated states. Dibutyryl cyclic (DBc) AMP also attenuated the migration of monocytes under basal as well as histamine-stimulated states. Both PGE2 and DBcAMP also attenuated the IL-1 beta-stimulated migration of monocytes. Angiotensin II, endothelin-1, and platelet-activating factor did not modulate the migration of monocytes.",
            "output": [
                "Do vasoactive agents modulate migration of monocytes across glomerular endothelial cells?"
            ]
        },
        {
            "id": "task847-63c66c49869e4a4e9f80ff7087d46d69",
            "input": "To investigate the alteration of the retinal nerve fiber thickness (NFLT) before and after vitreous surgery for a macular hole in cases with or without visual field defects.', 'The NFLT of 23 eyes with idiopathic macular hole was measured with scanning laser polarimeter upto 12 months after surgery. The NFLT was divided into superior, inferior, nasal, and temporal quadrants. The mean NFLT of each quadrant was analyzed statistically and compared to the results of visual field tests.', 'In all cases, the NFLT decreased significantly upto 3 months after surgery, but increased gradually upto 12 months. In cases with visual field loss, the thickness of the nerve fiber layer that corresponds to the visual field defect diminished strongly, in contrast with other quadrants. Even in cases without visual field loss, the NFLT decreased significantly a month after surgery, especially in the nasal and inferior quadrants.",
            "output": [
                "Does [ Thickness of retinal nerve fiber layer decrease after vitreous surgery for idiopathic macular hole ]?"
            ]
        },
        {
            "id": "task847-a314c32c75544b378b43a56796b86aa5",
            "input": "Aging of the skin is affected by intrinsic and extrinsic factors. Especially important extrinsic factor is ultraviolet radiation, which causes premature aging of the skin. Intrinsic aging is influenced by genetic factors, and changes in hormones. In menopause, changes in hormonal balance have been suggested to enhance aging of the skin.",
            "output": [
                "Do systemic estrogens have no conclusive beneficial effect on human skin connective tissue?"
            ]
        },
        {
            "id": "task847-0e5db84923bd4c7fad8a8bce2d836216",
            "input": "Conventional pulsatile (CP) roller pump cardiopulmonary bypass (CPB) was compared to computer controlled biologically variable pulsatile (BVP) bypass designed to return beat-to-beat variability in rate and pressure with superimposed respiratory rhythms. Jugular venous O2 saturation (SjvO2) below 50% during rewarming from hypothermia was compared for the two bypass techniques. A SjvO2 less than 50% during rewarming is correlated with cognitive dysfunction in humans.', 'Pigs were placed on CPB for 3 hours using a membrane oxygenator with alpha-stat acid base management and arterial filtration. After apulsatile normothermic CPB was initiated, animals were randomized to CP (n = 8) or BVP (roller pump speed adjusted by an average of 2.9 voltage output modulations/second; n = 8), then cooled to a nasopharyngeal temperature of 28 degrees C. During rewarming to stable normothermia, SjvO2 was measured at 5 minute intervals. The mean and cumulative area for SjvO2 less than 50% was determined.', 'No between group difference in temperature existed during hypothermic CPB or during rewarming. Mean arterial pressure, arterial partial pressure O2, and arterial partial pressure CO2 did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. The range of systolic pressure was greater with BVP (41 +/- 18 mm Hg) than with CP (12 +/- 4 mm Hg). A greater mean and cumulative area under the curve for SjvO2 less than 50% was seen with CP (82 +/- 96 versus 3.6% +/- 7.3% x min, p = 0.004; and 983 +/- 1158 versus 42% +/- 87% x min; p = 0.004, Wilcoxon 2-sample test).",
            "output": [
                "Does biologically variable pulsation improve jugular venous oxygen saturation during rewarming?"
            ]
        },
        {
            "id": "task847-04d2e0d35c8a447f815d5930fe5ba3f5",
            "input": "Substaging of T1 bladder tumors into T1a and T1b based on invasion of the tumor superficial to and beyond the muscularis mucosa has been assigned prognostic significance. We determined whether outcomes after intravesical bacillus Calmette-Guerin (BCG) differ between stage T1a and T1b subcategories.', 'Retrospective pathological evaluation of the initial transurethral resection specimens of stage T1 bladder tumors was performed by 2 pathologists. Grade 1, 2 or 3 and stage T1a or T1b were assigned to each case. Followup was from the date of transurethral resection to date of death or the last visit. Kaplan-Meier probability and log rank test were used to evaluate recurrence and progression.', 'Substaging was performed in 49 of the 55 patients (89%) with stage T1 disease. Disease was stage T1a in 32 (65%), stage T1b in 17 (35%), grade 3 in 45 (92%) and grade 2 in 4 (8%) cases. Maximum followup was 147 months (median 71) and 28 cases had a minimum of 5 years of followup. Recurrence was noted in 33 cases (67.3%), including 22 stage T1a (69%) and 11 stage T1b (65%), at a median followup of 11.3 and 8.6 months, respectively. Progression to a higher stage of disease was recorded in 12 cases (24.4%), including 7 (22%) stage T1a and 5 (29%) stage T1b, at a median followup of 108 and 120 months, respectively. The difference between T1a and T1b subcategories was not statistically significant in regard to recurrence-free (p = 0.7203) and progression-free (p = 0.574) outcomes.",
            "output": [
                "Are outcomes after intravesical bacillus Calmette-Guerin affected by substaging of high grade T1 transitional cell carcinoma?"
            ]
        },
        {
            "id": "task847-98c64d3c37d44059ae9c3dbcecd2428c",
            "input": "To determine the effect of castration on hippocampal function, we have investigated synaptic transmission in the castrated male mouse in vivo. We also examined whether administering testosterone can reverse the changes.', 'Male 12 weeks-old C57BL/6J mice were divided into three experimental groups; sham-castration (Control), the castration group (Cast), and the castration plus testosterone propionate group (Cast+TP). Field excitatory postsynaptic potentials (fEPSP) were evoked in the CA1 area of the hippocampus by stimulating the commissural fibers of the contralateral hippocampus. Field EPSPs were evoked in the granular cells of the dentate gyrus (DG) by stimulating the ipsilateral perforant path fibers.', 'Laminar analysis of the fEPSPs in the hippocampal CA1 pyramidal cell layer did not differ significantly between the three experimental groups. However, paired pulse facilitation (PPF) of the fEPSP with short inter-stimulus intervals (30 to 100 msec) was significantly suppressed in Cast group. This suppression was reversed by testosterone injection (Cast+TP). Longterm potentiation (LTP) in the CA1 pyramidal neurons by high frequency stimulation (HFS) did not differ significantly between the three experimental groups, whereas potentiation evoked by primed burst stimulation (PBS) was much weaker in the Cast group compared with the Control group. Testosterone injection restored the PBS-induced potentiation to the control level. Synaptic transmission between perforant pathway and the granule cells in the dentate gyrus (DG) did not differ significantly among the three experimental groups.",
            "output": [
                "Is altered synaptic transmission in the hippocampus of the castrated male mouse reversed by testosterone replacement?"
            ]
        },
        {
            "id": "task847-c25d70467d31478dae1da04088f94de1",
            "input": "Intrathecal magnesium sulfate coinfusion with morphine increases antinociception in normal rats; however, because magnesium also delays the onset of tolerance, it is not clear whether this additional antinociception is a result of potentiated analgesia or tolerance abatement. We examined the antinociceptive interaction of intrathecal (IT) bolus magnesium sulfate and morphine in morphine naive rats and those with mechanical allodynia after a surgical incision. After intrathecal catheter implantation, rats were given preinjections of magnesium or saline, followed by injections of morphine or saline. In morphine na\u00efve rats, IT bolus magnesium sulfate 281 and 375 microg followed by IT morphine 0.25 or 0.5 nmol enhanced peak antinociception and area under the response versus time curve two-to-three-fold in the tail-flick test as compared with morphine alone. Likewise, in rats with incisional pain, IT bolus magnesium sulfate 188 and 375 microg followed by morphine 0.5 nmol reduced mechanical allodynia, whereas morphine 0.5 nmol alone did not. This study suggests that IT magnesium sulfate potentiates morphine at a spinal site of action.",
            "output": [
                "Does magnesium sulfate potentiate morphine antinociception at the spinal level?"
            ]
        },
        {
            "id": "task847-c6f75f41412e496fa83efaf280dfb615",
            "input": "Fetal brain temperature has been found to decrease during hypoxia, strongly suggesting a reduction in cerebral O2 consumption and increases in cerebral blood flow. These responses may protect the brain in part against hypoxic injury. This study was undertaken to examine whether these compensatory mechanisms are lost during fetal hyperthermia.', 'Intermittent fetal hypoxemia was induced by administering low-O2 gas mixtures to nine near-term ewes. Fetal brain and body core temperature responses were measured with and without fetal hyperthermia induced by circulating warm water through a plastic coil looped about the fetus in utero.', 'In normothermic fetuses, fetal brain temperature relative to core decreased during a 30-minute period of hypoxia and then returned to normal during recovery. This response may be explained by a combination of cerebral hypometabolism and increased cerebral blood flow. However, in hyperthermic fetuses (intrauterine warming for 1 hour, raising body core and brain temperatures 0.66 +/- 0.06 and 0.61 +/- 0.10 C, respectively) a subsequent period of hypoxia no longer induced a reduction in brain temperature relative to body core.",
            "output": [
                "Does hyperthermia prevent metabolic and cerebral flow responses to hypoxia in the fetal sheep?"
            ]
        },
        {
            "id": "task847-57c3642f950b4aaebfc9288b86adfe54",
            "input": "CD44 is a cell surface glycoprotein widely distributed in the extracellular matrix. CD44 isoforms arising from alternative mRNA splicing are implicated in tumor metastases. The aim of this study is to investigate the expression of CD44s and two splice variants, CD44-9v and CD44-10v, in squamous cell carcinoma (SCC) of the vulva as well as its correlation with lymph node (LN) metastases and disease-free survival.', 'Thirty-five SCC vulvar tumors were evaluated for CD44s, CD44-9v, and CD44-10v expression by immunocytochemistry. One nonmetastatic LN was studied also. In cases with LN metastases, the metastatic LN as well as a nonmetastatic LN from the same patient were evaluated.', 'CD44s and CD44-9v were expressed in all epithelia--normal, dysplastic, and SCC. However, intensity and distribution of expression of 9v isoforms changed within the tissue containing invasive cancer. CD44-9v expression was downregulated in the most differentiated cells within the carcinoma, mainly in patients who had disease recurrence or eventually died of disease (P = .031). All metastatic tumor to LNs was immunoreactive also for CD44-9v. CD44-10v expression was present in 78% of tumors and 56% of normal epithelium. Interestingly, CD44-10v membrane expression, but not cytoplasmic expression, correlated with disease recurrence (P = .035).",
            "output": [
                "Are cD44-9v and CD44-10v potential molecular markers for squamous cell carcinoma of the vulva?"
            ]
        },
        {
            "id": "task847-d917300f05294bbd87036c1711491842",
            "input": "Recent data provide evidence of a systemic inflammatory response in severe acute pancreatitis; in contrast, the exact immune mechanisms underlying chronic pancreatitis remain unclear.', 'To investigate the immune response in the clinical features of chronic pancreatitis, we investigated the gene expression of tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor receptor (TNFR)-p55 and -p75 and inducible nitric oxide synthase (iNOS) in peripheral blood mononuclear cells (PBMC) of 18 patients with late-stage alcoholic chronic pancreatitis of different disease activity (Balthazar criteria).', 'Semiquantitative reverse transcriptase-polymerase chain reaction revealed a significantly enhanced gene expression of TNF-alpha (P < 0.05), TNFR-p55 (P < 0.05) and TNFR-p75 (P < 0.01) in unstimulated PBMC of patients with advanced chronic pancreatitis (11/18 with calcifications) compared to healthy controls (n = 8). No significant difference was found between patients with mild acute pancreatitis and patients with an inactive quiescent pancreatitis. Moreover, no expression of inducible nitric oxide synthase was detectable.",
            "output": [
                "Does cytokine gene expression in peripheral blood mononuclear cells reflect a systemic immune response in alcoholic chronic pancreatitis?"
            ]
        },
        {
            "id": "task847-98bf38bb08794cfe85ca34f0ecf479bd",
            "input": "Severity of pancreatitis seems to be aggravated by impairment of vascular perfusion of the gland. Early mortality occurs within the first few days from the acute consequences of pancreatic injury with subsequent inflammatory response. Because vasoactive substances, including endothelin, seem to contribute to early mortality in acute pancreatitis, we tested the hypothesis that the inhibition of endothelin action could alter the outcome after severe experimental pancreatitis.', 'In two groups of rats, pancreatitis was induced by intraductal infusion into the pancreatic duct of 1 microL/g body weight (b.w.) of either a 4% or a 5% sodium taurocholate solution. The mixed endothelin A and endothelin B receptor antagonist bosentan (20 mg/kg b.w.) or vehicle was injected intravenously in 12-h intervals for 3 d starting 1 h after induction of bile acid pancreatitis. This dose of bosentan is known to completely inhibit the effect of exogenous endothelin. The survival rate was monitored for 7 d. Thereafter, the surviving rats were sacrificed and the pancreas was prepared for histological and biochemical evaluation.', 'Irrespective of the treatment protocol (bosentan versus saline), survival was not different in animals challenged with either 4% or 5% sodium taurocholate. The corresponding survival rates were 62% with bosentan and 77% without bosentan in the 4% sodium taurocholate group. In the 5% sodium taurocholate group, the survival rates were 20% with and 27% without bosentan. Morphological and biochemical alterations were identical in control as well as in endothelin-antagonist-treated rats.",
            "output": [
                "Does the endothelin antagonist bosentan improve survival in severe experimental pancreatitis in rats?"
            ]
        },
        {
            "id": "task847-2da91d28fe9a43f18a8248e1903fa1d0",
            "input": "To identify injured cells in the liver of patients with primary biliary cirrhosis (PBC) and to determine the effects of ursodeoxycholic acid (UDCA) on these cells, we examined the cellular expression of heat shock proteins (HSPs) in PBC both before and after treatment with UDCA.', 'Expression of HSP70 and ubiquitin in PBC livers (n=34) was evaluated immunohistochemically as well as by immunoblot analysis, and compared with chronic viral hepatitis type C (n= 9), primary sclerosing cholangitis (n=8), and controls (n=7).', 'Immunoblot analysis demonstrated a marked expression of HSP70 and ubiquitin in PBC. Immunohistochemical staining for both HSP70 and ubiquitin was observed to be strong in biliary epithelial cells (BECs) and moderate in both hepatocytes and arteries in PBC. Cellular labelling rates for HSP70 and ubiquitin of bile ducts in PBC were significantly higher (p<0.01) than those in chronic viral hepatitis type C, primary sclerosing cholangitis, or controls. The labelling rates for HSP70 and ubiquitin in bile ducts and in hepatocytes were significantly decreased (p<0.01) after treatment with UDCA in PBC.",
            "output": [
                "Does ursodeoxycholic acid reduce expression of heat shock proteins in primary biliary cirrhosis?"
            ]
        },
        {
            "id": "task847-82e6c8b27cf4405da3bc5fd751509d2e",
            "input": "Short-term estrogen administration improves vasodilation and has been shown to improve exercise capacity. However, it is unknown whether long-term estrogen replacement therapy is associated with improved exercise capacity in postmenopausal women without known coronary artery disease.', 'We studied 248 postmenopausal women without known coronary artery disease (mean age 63.5 years); 158 (64%) were current or past hormone replacement therapy (HRT) users and 108 (44%) were current users of HRT. Attributes potentially affecting exercise capacity and cardiac risk factors were carefully measured. These included duration of estrogen replacement therapy, all variables in the Framingham risk index, physical activity level, body mass index, waist-to-hip ratio, presence of osteoporosis, and family history of heart disease. We measured maximal oxygen uptake (MVO (2)) and anaerobic threshold as objective markers of exercise capacity. The relation between exercise capacity and use of HRT was analyzed with the use of logistic regression, controlling for confounding variables. We found that fitness, as measured by MVO (2) and anaerobic threshold, was significantly greater in women who had used HRT currently or in the past compared with women who had never used HRT. This difference in fitness was not confounded by age or physical activity level.",
            "output": [
                "Is long-term estrogen replacement therapy associated with improved exercise capacity in postmenopausal women without known coronary artery disease?"
            ]
        },
        {
            "id": "task847-aa525725a1e64bd991ea167bb794f044",
            "input": "We investigated the influence of exocrine tissue contamination on the process of vascularization of isolated pancreatic islets of Langerhans after free transplantation into Syrian golden hamsters.', 'After isolation by a modified collagenase digestion technique, a total of 45 individual islets contaminated with exocrine tissue were transplanted syngeneically into striated muscle of dorsal skinfold chambers of nine animals. Sixty-six purified islet grafts transplanted into nine additional animals served as controls. Islet engraftment as well as the process of angiogenesis and revascularization were analyzed at days 3, 5, 9, and 13 after transplantation using intravital fluorescent microscopic techniques.', \"Islet grafts contaminated with exocrine tissue showed a significantly (P<0.05) lower take rate initially after transplantation when compared with purified islet grafts. In addition, functional capillary density, which served as an indicator of graft vascularization, was found significantly (P<0.05) decreased in contaminated compared with purified islets. Exocrine tissue contamination was further associated with marked leukocyte-endothelial cell interaction within the grafts' postcapillary venules, which finally resulted in six of nine animals in an overwhelming unspecific inflammation of the transplantation site with successive loss of the islet transplants.",
            "output": [
                "Does exocrine contamination of isolated islets of Langerhans deteriorate the process of revascularization after free transplantation?"
            ]
        },
        {
            "id": "task847-2afd3fa055214a798b9ada8a65242510",
            "input": "The purpose of the present study was to investigate the effect of the C1 esterase inhibitor (C1-INH) molecule against human complement attack on a swine endothelial cell (SEC) membrane. Human C1-INH functions as an inhibitor for complement reaction in the first step of the classical pathway in the fluid phase.', 'A surface-bound form of human C1-INH (C1-INH-PI) consisting of a full-length coding sequence of C1-INH and a glycosylphosphatidylinositol (GPI) anchor of the decay-accelerating factor (CD55) was constructed, and stable Chinese hamster ovarian tumor (CHO) cell lines and SEC lines expressing C1-INH-PI were then prepared by transfection of the constructed cDNA. The basic function of the transfected molecules on the xenosurface was investigated using CHO transfectants for the sake of convenience. The efficacy of C1-INH-mediated protection of SEC from human complement was then assessed as an in vitro hyperacute rejection model of a swine-to-human discordant xenograft.', 'Flowcytometric profiles of the stable CHO and SEC transfectants with C1-INH-PI showed a medium level of expression of these molecules. The C1-INH levels were significantly reduced as a result of phosphatidylinositol-specific phospholipase C (PI-PLC) treatment, suggesting that the molecules were present as the PI-anchor form. Approximately 51.3 x 10(4) and 13.3 x 10(4) molecules of C1-INH-PI blocked human complement-mediated cell lysis by approximately 75% on the CHO cell and by 60-65% on the SEC cell, respectively. In addition, the complement-inhibiting activity of human C1-INH molecules is not homologously restricted.",
            "output": [
                "Does a surface-bound form of human C1 esterase inhibitor improve xenograft rejection?"
            ]
        },
        {
            "id": "task847-d6b759c3f97d48d289894ae860d2a0e1",
            "input": "CTLA4IgG that binds to B7 effectively inhibits the signaling of CD28/B7 pathway and induces antigen-specific T-cell unresponsiveness in vitro and in vivo. We examined whether the development of obliterative bronchiolitis in a murine heterotopic airway transplantation model is T cell dependent and whether CTLA4IgG abrogates the development of obliterative bronchiolitis.', 'Tracheae with main bronchi from C3H/He (H2k), BALB/C (H2d), or C57BL/6 (H2b) mice were transplanted heterotopically into subcutaneous pockets on the backs of BALB/C or BALB/C nu/nu mice on day 0. Recipient mice were untreated or intraperitoneally treated with either CTLA4IgG or human IgG with different time and dose schedules.', 'The development of obliterative bronchiolitis, which leads to luminal obliteration by fibrous tissue in a murine heterotopic airway transplantation model, was T cell dependent and the development of obliterative bronchiolitis was significantly abrogated by the CTLA4IgG treatment. However, the normal ciliated columnar respiratory epithelial cells in allografts were lost and replaced by flattened attenuated epithelial cells even after the CTLA4IgG treatment. We further demonstrated that CTLA4IgG treatment did not result in the induction of donor-specific unresponsiveness.",
            "output": [
                "Does blocking the CD28-B7 T-cell costimulatory pathway abrogate the development of obliterative bronchiolitis in a murine heterotopic airway model?"
            ]
        },
        {
            "id": "task847-cf1a4ebb9a1d42c084ca49dacaa5db7a",
            "input": "For high-resolution microscopy, cells have to be analyzed through thin glass coverslips. Therefore, it is necessary to culture cells on coverslips for preservation of cell morphology. We found cell attachment and spreading to be relatively slow processes, even when cells were plated on coated coverslips. This slowness presents a problem, particularly when synchronized cell populations are used.', 'In this paper, we present a method that is based on glow-discharged carbon coating of coverslips which promotes rapid attachment and spreading of cells, enabling rapid analysis of cells after plating. Results obtained with carbon-coated coverslips were compared with those of other types of coating. Two fibroblast lines, an epithelial cell line, and a carcinoma cell line were tested.",
            "output": [
                "Does coating of coverslips with glow-discharged carbon promote cell attachment and spreading probably due to carboxylic groups?"
            ]
        },
        {
            "id": "task847-9d8843d8575d4ae5b3f89b44841bc142",
            "input": "Sequential events of endometrial tumorigenesis can be studied by comparison of genetic lesions seen in normal, premalignant, and malignant tissues. The distribution of k-ras mutations in microsatellite stable and unstable premalignant lesions was studied to determine whether this gene is implicated in both tumorigenic pathways.', 'K-ras mutations were analysed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing in matched endometrial normal, premalignant (atypical hyperplasias), and adenocarcinoma tissues from individual patients. Identification of precancers solely by their appearance as atypical endometrial hyperplasias is very subjective; therefore, in addition to histopathological assessment, we performed molecular testing (non-random X inactivation or clonal altered microsatellites) for an expected feature of precancers--that is, monoclonality.', 'Equivalent K-ras mutation frequencies were seen in microsatellite stable (six of 33) and unstable (three of 23) cancers. In both types, K-ras mutation in monoclonal precancers usually corresponded to a change from normal to an equivocal (two of 12) or hyperplastic (10 of 12) histology. Divergent K-ras genotypes among multiple neoplastic tissues of individual patients (two of six patients) are exceptions explained either by multicentric premalignant disease, or acquisition of K-ras mutation late in neoplastic progression.",
            "output": [
                "Do k-ras mutations appear in the premalignant phase of both microsatellite stable and unstable endometrial carcinogenesis?"
            ]
        },
        {
            "id": "task847-b60ec0a135504e2f96a8485ff646de86",
            "input": "The ability of tissues to take up naked plasmid DNA in vivo suggests an approach for reconstituting systemic metabolic deficiencies without the disadvantages of viral vectors and lipid-DNA complexes. Plasmid-mediated gene transfer into skeletal muscle was investigated as a means of providing a therapeutic source of insulin.', 'Four plasmid constructs, each bearing a mouse furin cDNA transgene and rat proinsulin cDNA (modified for processing by furin) driven by four different promoters were injected into the calf muscles of male Balb/c mice. Insulin and C-peptide concentrations were measured by radio-immunoassays having minimal crossreactivity for proinsulin and partially processed proinsulin.', 'Intramuscular insulin concentrations increased by up to 3.6-fold over controls seven days after single injections of CMV, beta-actin, hsp70 and myoglobin promoter constructs. The optimal dose for most constructs was 100 micrograms plasmid DNA. Intramuscular plasmid injection into streptozotocin-induced diabetic Balb/c mice raised plasma insulin and C-peptide concentrations, and reduced hyperglycaemia. Two injections (100 micrograms plasmid DNA each) caused higher plasma insulin concentrations and significantly reduced hyperglycemia in diabetic mice than a single injection. Best results were obtained when plasmid injections preceded induction of diabetes by 14 days.",
            "output": [
                "Does naked plasmid-mediated gene transfer to skeletal muscle ameliorate diabetes mellitus?"
            ]
        },
        {
            "id": "task847-1ec1431b2f664ac2804ae7d0df26cd21",
            "input": "To investigate the significance of the presence or absence of the thymus in the development of pulmonary hypertension (PH) following monocrotaline (MCT) administration, the degree of MCT-induced PH (MCT-PH) in athymic nude (F344/N Jcl-rnu) rats was compared with that in their euthymic (rnu/+) littermates.', \"Histopathological studies of the lung in terms of interstitial edema, congestion, thickening of the alveolar wall, inflammatory cell infiltration and degeneration of arteries were performed by staining with hematoxylin-eosin (HE), elastin van Gieson and Masson's trichrome. The medial wall thickness of the small pulmonary arteries and the weight ratio of the right ventricular free wall (RV) to that of the left ventricle plus septum [RV/(LV + S) weight ratio] were used as indices of the degree of PH. Toluidine blue staining was performed to estimate the number of the mast cells in the lung interstitium.\", 'Interstitial edema was significantly severer in MCT- injected euthymic rats than in MCT-injected athymic nude rats (p < 0.01); in contrast, the thickening of the alveolar wall was severer in MCT-injected athymic nude rats than in MCT-injected euthymic rats (p < 0.05). The degree of MCT-PH, as determined by the medial wall thickness of the small pulmonary arteries and RV/(LV + S) weight ratio in MCT-injected athymic nude rats, was significantly severer than in MCT-injected euthymic rats (p < 0.05 and p < 0.01, respectively). The number of mast cells was significantly greater in MCT-injected athymic nude rats than in MCT-injected euthymic rats (p < 0.01). The degree of the medial wall thickness of the small pulmonary arteries was significantly correlated with RV/(LV + S) weight ratio (p < 0.05) as well as with the number of mast cells in MCT-injected rats.",
            "output": [
                "Do athymic nude rats develop severe pulmonary hypertension following monocrotaline administration?"
            ]
        },
        {
            "id": "task847-f6e898ebab80411b85ff207d7cba50f2",
            "input": "The Epicoccum nigrum (EN) extract used in allergy disorders exhibits batch-to-batch variations in protein composition and allergenic potency. In this study, the allergens of EN grown in different media were investigated.', \"EN was grown in five different nutrient media as stationary cultures at 25 degrees C for 5-23 days. The growth pattern was characterized by measuring dry weight, protein and carbohydrate content. The antigenic and allergenic content of EN extract was evaluated with EN-positive patients' sera and antibodies raised in rabbit.\", \"The growth of EN in Czapeck Dox medium yielded insufficient material, while Sabouraud's broth with yeast extract (SBY) gave maximum spore-mycelial mass and protein content. Potato dextrose broth (PDB) and potato dextrose agar (PDA) showed higher dry weight and protein in 7-9-day cultures. SDS-PAGE resolved 26, 22, and 21 protein bands in EN extracts from cultures of day-13 SBY, day-7 PDB, and day-9 PDA, respectively. IgE/IgG immunoblots showed more allergenic (25)/antigenic (25) bands in EN cultured in SBY than in the others. Specific IgE ELISA and intradermal tests showed EN extract from day-13 culture in SBY to be the most potent.",
            "output": [
                "Do allergens of Epicoccum nigrum grown in different media for quality source material?"
            ]
        },
        {
            "id": "task847-a2f1b196cffb42fe8960319a3abb8dc5",
            "input": "An event-related brain potential (ERP) study investigated how different processing stages involved in face identification are reflected by ERP modulations, and how stimulus repetitions and attentional set influence such effects.', 'ERPs were recorded in response to photographs of familiar faces, unfamiliar faces, and houses. In Part I, participants had to detect infrequently presented targets (hands), in Part II, attention was either directed towards or away from the pictorial stimuli.', \"The face-specific N170 component elicited maximally at lateral temporal electrodes was not affected by face familiarity. When compared with unfamiliar faces, familiar faces elicited an enhanced negativity between 300 and 500 ms ('N400f') which was followed by an enhanced positivity beyond 500 ms post-stimulus ('P600f'). In contrast to the 'classical' N400, these effects were parietocentrally distributed. They were attenuated, but still reliable, for repeated presentations of familiar faces. When attention was directed to another demanding task, no 'N400f' was elicited, but the 'P600f' effect remained to be present.",
            "output": [
                "Do event-related brain potentials distinguish processing stages involved in face perception and recognition?"
            ]
        },
        {
            "id": "task847-f782d293b51e4f64bf36f8907e3aaa5b",
            "input": "Spinally elicited peripheral nerve responses, commonly called neurogenic motor evoked potentials (NMEPs), are widely used to monitor spinal cord motor function during surgery. However, numerous evidence suggests that these responses are primarily sensory rather than motor. The collision technique was utilized to address this issue.', 'Collision studies were performed in 7 patients during surgery. An ascending volley of sensory (AS) and motor activity (AM) was elicited by posterior tibial nerve stimulation at the popliteal fossa. After a short time delay, high cervical spinal stimulation produced a descending volley of sensory (DS) and motor (DM) activity. The AM volley ascended only to the anterior horn cells whereas the AS and DS volleys collided in the spinal cord. The inter-stimulus delays were varied so as to affect the degree of spinal cord collision. The DS and DM activity which remained after collision was recorded from the posterior tibial nerves at the ankle.', 'Inter-stimulus delays of 18 ms or less resulted in no apparent peripheral descending volleys. These findings were consistent for all the patients studied.",
            "output": [
                "Are spinally elicited peripheral nerve responses sensory rather than motor?"
            ]
        },
        {
            "id": "task847-5d19d8c08d7a449da8766d6ea2637d19",
            "input": "To test the feasibility of scanning laser densitometry with a modified Rodenstock scanning laser ophthalmoscope (SLO) to measure the rod and cone photopigment distribution in patients with retinal diseases.', 'Scanning laser densitometry was performed using a modified Rodenstock scanning laser ophthalmoscope. The distribution of the photopigments was calculated from dark adapted and bleached images taken with the 514 nm laser of the SLO. This wavelength is absorbed by rod and cone photopigments. Discrimination is possible due to their different spatial distribution. Additionally, to measure retinal sensitivity profiles, dark adapted two color static perimetry with a T\u00fcbinger manual perimeter was performed along the horizontal meridian with 1 degree spacing.', 'A patient with retinitis pigmentosa had slightly reduced photopigment density within the central +/- 5 degrees but no detectable photopigment for eccentricities beyond 5 degrees. A patient with cone dystrophy had nearly normal pigment density beyond +/- 5 degrees, but considerably reduced photopigment density within the central +/- 5 degrees. Within the central +/- 5 degrees, the patient with retinitis pigmentosa had normal sensitivity for the red stimulus and reduced sensitivity for the green stimulus. There was no measurable function beyond 7 degrees. The patient with cone dystrophy had normal sensitivity for the green stimulus outside the foveal center and reduced sensitivity for the red stimulus at the foveal center. The results of color perimetry for this patient with a central scotoma were probably influenced by eccentric fixation.",
            "output": [
                "Do scanning laser densitometry and color perimetry demonstrate reduced photopigment density and sensitivity in two patients with retinal degeneration?"
            ]
        },
        {
            "id": "task847-fcac0d7431924e4fab2466a9fff4be94",
            "input": "A descriptive case review.', 'To assess the outcomes of anterior lumbar interbody fusion for painful discs within a solid posterolateral spinal fusion.', 'Some patients continue to have pain after posterolateral spinal fusion despite apparently solid arthrodesis. One potential etiology is pain that arises from a disc within the fused levels.', 'Retrospective review of 176 patients with anterior interbody fusion, which located 20 who had anterior interbody fusion levels of prior posterolateral spinal fusion. All had low back pain, solid posterolateral spinal fusion, and painful disc(s) at the posterolateral spinal fusion level(s) but not elsewhere. Pain was measured by the Numerical Rating Scale, function by Oswestry Disability Questionnaire, and patient satisfaction by the North American Spine Society Outcome Questionnaire.', 'Follow-up data were available for 18 patients (90%). Mean follow-up was 58 months (25 to 102). There were 10 men and 8 women. Mean age was 45 years (26 to 72). Diagnoses were degenerative discs, herniated nucleus pulposus, spondylolisthesis, and spinal stenosis. Eight patients had injuries after the previous posterolateral spinal fusion that precipitated new symptoms. Two patients had one level fusion, 14 had two levels, and 1 each had three and four levels. Four patients had one prior surgery, 5 had two, and 9 had three or more. All patients had solid anterior interbody fusion by radiograph. Mean Numerical Rating Scale improved from 7.9 before surgery to 4.7 after (P< 0.001). Mean Oswestry Disability Questionnaire improved from 56.3 before surgery to 47.9 after (P = 0.04). Of 15 patients unable to work before anterior interbody fusion, 5 returned to work. Sixteen patients (89%) were satisfied with their results.",
            "output": [
                "Does anterior lumbar fusion improve discogenic pain at levels of prior posterolateral fusion?"
            ]
        },
        {
            "id": "task847-ef524ebc902e40ff8e1cb1d80e539e5d",
            "input": "A cross-sectional study of spinal loading in healthy volunteers.', 'To measure the bending and compressive forces acting on the lumbar spine, in a range of postures, when unknown loads are delivered unexpectedly to the hands.', 'Epidemiologic studies suggest that sudden and unexpected loading events often lead to back injuries. Such incidents have been shown to increase back muscle activity, but their effects on the compressive force and bending moment acting on the spine have not been fully quantified. Furthermore, previous investigations have focused on the upright posture only.', 'In this study, 12 volunteers each stood on a force plate while weights of 0, 2, 4, and 6 kg (for men, 40% less for women) were delivered into their hands in one of three ways: 1) by the volunteer holding an empty box with handles, into which an unknown weight was dropped; 2) by the same way as in 1, but with volunteer wearing a blindfold and earphones to eliminate sensory cues; or 3) by the volunteer sliding a box of unknown weight off a smooth table. Experiments were carried out with participants standing in upright, partially flexed, and moderately flexed postures. Spinal compression resulting from muscular activity was quantified using electromyographic signals recorded from the back and abdominal muscles. The axial inertial force acting up the long axis of the spine was calculated from the vertical ground reaction force. The bending moment acting on the osteoligamentous spine was quantified by comparing measurements of lumbar curvature with the bending stiffness properties of cadaveric lumbar spines.', 'The contribution from abdominal muscle contraction to overall spinal compression was small (average, 8%), as was the axial inertial force (average, 2.5%), and both were highest in the upright posture. Peak bending moments were higher in flexed postures, but did not increase much at the moment of load delivery in any posture. Peak spinal compressive forces were increased by 30% to 70% when loads were suddenly and unexpectedly dropped into the box, and by 20% to 30% when they were slid off the table, as compared with loads simply held statically in the same posture (P < 0.001). The removal of audiovisual cues had little effect.",
            "output": [
                "Does sudden and unexpected loading generate high forces on the lumbar spine?"
            ]
        },
        {
            "id": "task847-5f213ab442ea4065a134cb422da75d07",
            "input": "Although glucose uptake is increased in chronically hypoperfused, viable myocardium, the dynamic changes in glucose uptake relative to oxygen consumption in \"short-term\" models of hibernation have not been fully explored.', '14 anesthetized swine were instrumented with an hydraulic occluder and flow probe on the proximal LAD artery. Blood flow was reduced approximately 30% for 1 hour. Myocardial blood flow and uptake of oxygen, free fatty acids, glucose and lactate were determined in the LAD region at baseline and at 10, 30, and 60 minutes of ischemia. Transmural biopsies for ATP and creatine phosphate (CP) were obtained in the LAD region prior to and at 15 and 45 minutes of ischemia. In 5 animals, glycogen was assayed at baseline and at the end of 60 minutes of ischemia.', 'In the LAD region, myocardial oxygen consumption was reduced from 2.06 +/- 0.16 micromol/min/gram to 1.46 +/- 0.13 micromol/min/gram (P < 0.05). By 15 minutes of ischemia, transmural creatine phosphate fell from 7.48 +/- 0.76 micromol/g-wet weight at baseline to 6.19 +/- 0.32 micromol/g-wet weight (P < 0.05) but normalized by 45 minutes of ischemia (7.39 +/- 0.56 micromol/g-wet weight; NS). Between 10 and 60 minutes of constant flow reduction, glucose uptake as a percentage of MVO2 increased from 3 +/- 2% to 10 +/- 2% (P < 0.05) while lactate uptake increased from -9 +/- 9% to -1 +/- 2% (P < 0.05). Glycogen decreased from 27.8 +/- 3.7 at baseline to 16.9 +/- 1.2 micromol/g-wet weight at end-ischemia.",
            "output": [
                "Does glucose uptake increase relative to oxygen consumption during short-term hibernation?"
            ]
        },
        {
            "id": "task847-d6b25f7c2aa24e8baf5a2ecaf3bd0704",
            "input": "To determine whether addition of basic fibroblast growth factor (bFGF), an angiogenic growth factor, enhances the angiogenic effects of transmyocardial laser revascularization (TMR).', 'TMR is an investigational therapy for treating patients with medically refractory angina not amenable to traditional therapies. Histologic and blood flow studies in animals have suggested that TMR enhances angiogenesis above that normally seen in ischemic myocardium. We tested the hypothesis that bFGF administered into TMR channels further enhance the angiogenic effects of TMR.', \"Chronic ischemia was created in 3 groups of dogs using an ameroid constrictor on the proximal LAD. In the bFGF group (n = 5) non-transmyocardial channels were created in the LAD territory and bFGF, (100 ng/ml) dissolved in pluronic gel was injected into the each channel. In the TMR group (n = 7), transmyocardial channels were created without bFGF. A control group (n = 7) had ischemia without TMR of bFGF. 5-bromo-2'-deoxyuridine (BrdU) was administered to mark proliferating cells. After 8 weeks survival, colored microspheres were injected to assess the regional myocardial blood flow.\", 'TMR and TMR+bFGF increased total vascular density by approximately 40% over that observed in the control group. However, the number of large vessels (internal diameter > or = 50 microm) was doubled by the addition of bFGF, and this correlated with a 50% increase in the density of proliferating vascular cells and a tripling of the total estimated vascular cross sectional area. Blood flow to the LAD territory was increased by TMR compared to controls, with no further benefit observed in the bFGF group.",
            "output": [
                "Does histologic evidence that basic fibroblast growth factor enhance the angiogenic effects of transmyocardial laser revascularization?"
            ]
        },
        {
            "id": "task847-9585bd207ae74c77827cc7184eee7cb1",
            "input": "Deep wound infections pose an increasing problem in cardiac surgery patients. Prospective infection monitoring is thus a means of identifying possible risk factors.', 'Within a period of 5 months, a total of 376 adult patients, 260 men and 116 women, with a mean age of 62.6 years (range 18-88), underwent coronary bypass grafting (n=281) or other cardiac surgery procedures (n=95). Nasal cultures were taken preoperatively from every patient, as well as cultures of the wound during surgery and when dressings were changed thereafter. In addition, nasal cultures were taken from all the medical and nursing staff. To differentiate endogenous and exogenous infection pathways, DNA fingerprint analysis was performed.', \"A total of 38 patients (10.1%) developed a wound infection, in 14 patients this happened to be a deep wound infection, in 24 patients a superficial one. Five sternal wound infections were associated with mediastinitis (1.3%). The occurrence of a wound infection overall resulted in prolonged hospitalization (29.4+/-24 vs. 11.9+/-6.9 days, P=0.001), but not in increased hospital mortality (4.4% vs. 3.9%). Obesity, diabetes mellitus and nasal carriage of Staphylococcus aureus proved to be independent risk factors with an odds ratio of 2.07, 2.26 and 2.28, respectively. In all but one of the sternal colonizations with S. aureus, DNA fingerprint analysis demonstrated an identical pattern of S. aureus from the patient's nose and sternum, indicating an endogenous infection pathway.",
            "output": [
                "Is the endogenous pathway a major route for deep sternal wound infection?"
            ]
        },
        {
            "id": "task847-d6948b33801f4d8db2c0524acde1f4f7",
            "input": "Outcome after correction of atrioventricular septal defect depends to a great deal on the postoperative function of the left atrioventricular valve. The related role of the zone of apposition ('cleft') has been debated: should it be closed (bileaflet repair) or should it be left untouched (trileaflet repair)? This study aims to answer the question by comparing the outcome of patients treated according to these two approaches.\", \"We reviewed all our patients who underwent repair of complete atrioventricular septal defect from 1984 to 1997 and selected those in whom the closure of the zone of apposition in principle would have been possible. Two groups with similar characteristics were constituted: group I (n=63), where the zone of apposition was deliberately not closed as part of a trileaflet repair (postoperative open zone of apposition) and group II (n=96), where it was electively closed as part of a bileaflet AV valve repair (closed zone of apposition). Since we changed from a trileaflet to a bileaflet repair in 1987, the two groups differ in terms of size and length of follow-up. Outcome was compared with regard to survival and freedom from reoperation for left atrioventricular valve incompetence. Late atrioventricular valve function was evaluated by Echo-Doppler. For statistical analysis, we used Chi-square or Fisher's exact test, the Mann-Whitney test and the log-rank test for comparison of Kaplan-Meier curves. The difference was considered statistically significant with a P-value of 0.05 or less.\", 'Early mortality was 9.5% (6/63) in group I and 3.1% (3/96) in group II (P=0.16). Actuarial survival after 1, 4 and 8 years was 80.4, 68.4 and 64.8%, respectively, for group I. Actuarial survival for group II was 94.7, 92.1 and 92.1% (P=0.0002). Freedom from reoperation for left atrioventricular valve regurgitation was 90.2, 85.6 and 77.8% for group I at the same time interval. It was a constant 97.9% for group II (P=0.0016). At reoperation, left atrioventricular valve regurgitation was present through the open zone of apposition in 63% of group I cases. The follow-up is 96% (126/131) complete. An increase in degree of left atrioventricular valve incompetence was noted in 28% (11/39) of group I cases and in 9% (8/87) of group II cases (P=0.0131).",
            "output": [
                "Does closure of the zone of apposition at correction of complete atrioventricular septal defect improve outcome?"
            ]
        },
        {
            "id": "task847-e0afa61905f749da86a7c4056098d548",
            "input": "Mild hyperhomocysteinaemia (HHC) is associated with an increased risk of premature atherothrombotic cerebrovascular disease. We investigated the clinical efficacy with regard to the incidence of cardiovascular events of treatment of mild HHC with vitamin B(6) plus folic acid.', 'We studied 224 consecutive patients with clinically manifest atherothrombotic cerebrovascular disease with onset before the age of 56. Follow-up was obtained in 203 (90.6%) patients. At baseline, 52 (25.6%) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B(6) (250 mg) plus folic acid (5 mg); 151 (74.4%) were normohomocysteinaemic (reference group).', 'During follow-up (median 57 months), 31 (20.5%) of the normo- and 11 (21.2%) of the hyperhomocysteinaemic patients had a new cardiovascular event. The crude incidence rate per person-year for any cardiovascular event was similar in both groups (0.043 [CI, 0.029-0.057] in the normo- vs. 0.045 [CI, 0.021-0. 069] in the hyperhomocysteinaemic group). Multivariate Cox-regression analyses showed that hypertension and cholesterol levels were associated with an increased risk of new cardiovascular events in the total group [relative risk [RR] (yes vs. no), 7.4 (3. 4-16.0) and RR (per 1 mmol/l), 1.9 (CI, 1.4-2.7)]. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.96 (CI, 0.48-1.92).",
            "output": [
                "Are normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia associated with similar risks of cardiovascular events in patients with premature atherothrombotic cerebrovascular disease . A prospective cohort study?"
            ]
        },
        {
            "id": "task847-aba37fa03c764e2dac5e2dad22a18619",
            "input": "Asymmetric patterns of frontal brain activity and brain corticotropin-releasing hormone (CRH) systems have both been separately implicated in the processing of normal and abnormal emotional responses. Previous studies in rhesus monkeys demonstrated that individuals with extreme right frontal asymmetric brain electrical activity have high levels of trait-like fearful behavior and increased plasma cortisol concentrations.', 'In this study we assessed cerebrospinal fluid (CSF) CRH concentrations in monkeys with extreme left and extreme right frontal brain electrical activity. CSF was repeatedly collected at 4, 8, 14, 40, and 52 months of age.', 'Monkeys with extreme right frontal brain activity had increased CSF CRH concentrations at all ages measured. In addition, individual differences in CSF CRH concentrations were stable from 4 to 52 months of age.",
            "output": [
                "Are cerebrospinal fluid corticotropin-releasing hormone levels elevated in monkeys with patterns of brain activity associated with fearful temperament?"
            ]
        },
        {
            "id": "task847-c557deca9ca3461e9a6c1ba6d57933e9",
            "input": "Phosphatidylinositol 4,5-bisphosphate (PIP(2)) has been implicated in the regulation of the actin cytoskeleton and vesicle trafficking. It stimulates de novo actin polymerization by activating the pathway involving the Wiskott-Aldrich syndrome protein (WASP) and the actin-related protein complex Arp2/3. Other studies show that actin polymerizes from cholesterol-sphingolipid-rich membrane microdomains called 'rafts', in a manner dependent on tyrosine phosphorylation. Although actin has been implicated in vesicle trafficking, and rafts are sites of active phosphoinositide and tyrosine kinase signaling that mediate apically directed vesicle trafficking, it is not known whether phosphoinositide regulation of actin dynamics occurs in rafts, or if it is linked to vesicle movements.\", 'Overexpression of type I phosphatidylinositol phosphate 5-kinase (PIP5KI), which synthesizes PIP(2), promoted actin polymerization from membrane-bound vesicles to form motile actin comets. Pervanadate (PV), a tyrosine phosphatase inhibitor, induced comets even in the absence of PIP5KI overexpression. PV increased PIP(2) levels, suggesting that it induces comets by changing PIP(2) homeostasis and by increasing tyrosine phosphorylation. Platelet-derived growth factor (PDGF) enhanced PV-induced comet formation, and these stimuli together potentiated the PIP5KI effect. The vesicles at the heads of comets were enriched in PIP5KIs and tyrosine phosphoproteins. WASP-Arp2/3 involvement was established using dominant-negative WASP constructs. Endocytic and exocytic markers identified vesicles enriched in lipid rafts as preferential sites of comet generation. Extraction of cholesterol with methyl-beta-cyclodextrin reduced comets, establishing that rafts promote comet formation.",
            "output": [
                "Does phosphatidylinositol 4,5-bisphosphate induce actin-based movement of raft-enriched vesicles through WASP-Arp2/3?"
            ]
        },
        {
            "id": "task847-0ccbf9f8ac0642e9a6b9ae5c98232399",
            "input": "To determine whether patients with a rapid rate of joint space narrowing (JSN) in the hip have higher initial bone mineral density (BMD) in the proximal femur and/or lumbar spine than corresponding patients with a slow rate of JSN.', 'Twenty-eight patients undergoing unilateral total hip replacement (THR) for osteoarthritis (OA), but whose contralateral hips were asymptomatic and had minimal or no radiographic OA, were evaluated. The contralateral proximal femur (i.e., non-operated hip) and lumbar spine were scanned by dual energy x-ray absorptiometry at baseline (prior to THR) and at 2 years. The rate of JSN was determined by serial longitudinal quantification of the joint spaces over the 2 year period following THR from conventional radiographs, and the patients were divided into a group with a slow rate of JSN (< or = 0.2 mm/yr, n = 20) and a group with a rapid rate of JSN (> 0.2 mm/yr, n = 8).', \"The baseline BMD z and t scores at the femoral neck, Ward's triangle, and lumbar spine of the patients with subsequent rapid rates of JSN were significantly higher than those of patients with slower rates (p < 0.05). There was no difference between the rapid and slow narrowers at the greater trochanter (p > 0.2). Age, sex, weight, height, body mass index, Kellgren- Lawrence scores, and initial joint space width were not significantly different between the 2 groups.",
            "output": [
                "Does bone mineral density vary as a function of the rate of joint space narrowing in the hip?"
            ]
        },
        {
            "id": "task847-c4413255be1946c19a3bff74541638a9",
            "input": "Galbeta1-4GlcNAcalpha2-6 sialyltransferase (ST6GalI) is an acute phase reactant whose release from cells can be induced by proinflammatory cytokines. Because patients with chronic renal failure have high circulating levels of proinflammatory cytokines, we hypothesized that patients on the renal transplant waiting list would have high circulating levels of ST6GalI, which might adversely affect post-transplant events.', 'Levels of ST6GalI were measured in the serum of 70 patients immediately before renal transplant; these were correlated with posttransplant events, such as delayed graft function and rejection.', 'The mean serum level of ST6GalI was significantly higher in the patients (3162+/-97 U) than in 19 controls (2569 +/- 125 U; P<0.003). Patients who required dialysis posttransplant for treatment of delayed graft function (n=20) had significantly higher levels of ST6GalI pretransplant (3735+/-228 U) than patients (n=50) who did not require dialysis (2933+/-83 U; P<0.0001). In a multivariate analysis the ST6GalI level and cold ischemic time were found to be independent risk factors for the development of delayed graft function.",
            "output": [
                "Do increased levels of GALbeta1-4GLCNACalpha2-6 sialyltransferase pretransplant predict delayed graft function in kidney transplant recipients?"
            ]
        },
        {
            "id": "task847-9f0ef1fe8bbc463c8b67195ea43840cf",
            "input": "Cell proliferation, vector titer and accessibility of target cells represent hurdles for efficient gene transfer to lung epithelia in vivo using recombinant murine leukemia (MuLV)-based retroviruses. We tested the hypothesis that the pulmonary epithelium is susceptible to retroviral-mediated gene transfer when stimulated to proliferate by a mitogen, keratinocyte growth factor (KGF).', 'Rats received keratinocyte growth factor (KGF, 2.5 micrograms/g x 4 doses, two consecutive days) intratracheally followed by high titer amphotropic retrovirus expressing beta-galactosidase. Gene transfer was assessed five days later.', 'KGF stimulated transient proliferation in the bronchiolar and alveolar epithelia (30-40% PCNA positive cells at peak) which decreased to background levels seven days after administration. Gene transfer to epithelia (X-Gal positive cells) occurred more frequently in KGF treated rats, but proliferation exceeded the level of gene transfer. X-gal positive cells were noted in the alveolar epithelium and occasionally in the bronchiolar epithelium. In order to understand the discrepancy between the number of proliferating and transduced cells, primary rat tracheal epithelium cultured at the air-liquid interface was infected from either the apical or basolateral side. Gene transfer was achieved only through basolateral application of vector, suggesting that epithelial polarity represents a barrier to MuLV-based lung gene transfer in vivo.",
            "output": [
                "Does keratinocyte growth factor induced epithelial proliferation facilitate retroviral-mediated gene transfer to distal lung epithelia in vivo?"
            ]
        },
        {
            "id": "task847-169fa654faa54bff87745de75b9027b8",
            "input": "Temperature increase, oxidative stress, and inflammatory reactions after endurance exercise were expected to stimulate the synthesis of heat shock proteins (HSP) in peripheral blood leukocytes. Furthermore, it was of interest whether regular endurance training influences HSP expression.', 'The expression of HSP27, HSP60, HSP70, constitutive HSC70, and HSP90 in the cytoplasma and surface of lymphocytes, monocytes, and granulocytes of 12 trained athletes was analyzed by flow cytometry before and after (0, 3, and 24 h) a half marathon. Twelve untrained persons at rest were included as control.', 'After the race, there was a significantly greater percentage of leukocytes expressing cytoplasmic HSP27, HSP60, and HSP70 (P < 0.01), whereas HSC70 and HSP90 remained unchanged. The fluorescence intensity increased significantly in monocytes for HSP27 (0 and 3 h) and HSP70 (0, 3, and 24 h) and in granulocytes, only 24 h postexercise for HSP70. The percent values of trained athletes at rest were significantly lower compared with untrained persons (P < 0,01).",
            "output": [
                "Is hSP expression in human leukocytes modulated by endurance exercise?"
            ]
        },
        {
            "id": "task847-d30d2fc82d9a4275b05a907b83add4d0",
            "input": "Prooxidant effects of fish oil supplementation could unfavorably affect the cardiovascular benefits of fish oil. We tested the effects of 8 wk vitamin E cosupplementation with fish oil on antioxidant defenses at rest and in response to exhaustive exercise in rats.', 'Rats (N = 80) were divided into fish oil, fish oil and vitamin E (FOVE), soy oil, and soy oil and vitamin E (SOVE) supplemented groups. For the vitamin E supplemented rats, corresponding groups (FOVE-Ex and SOVE-Ex) performed an acute bout of exhaustive exercise after the supplementation period.', 'Fish oil supplementation increased the activity of catalase, glutathione peroxidase, and glutathione-S-transferase in the liver and red gastrocnemius (RG) muscle. Fish oil decreased liver total glutathione (TGSH) levels. Vitamin E supplementation decreased antioxidant enzyme activities to levels at or near those in SOVE in a tissue specific pattern. Vitamin E increased TGSH in liver, heart, and RG. Regression analysis showed TGSH to be a negative determinant of protein oxidative damage as measured by protein carbonyl levels in both liver and RG. Catalase activity was associated with liver lipid peroxidation as measured by thiobarbituric acid-reacting substances. The exercise-induced decrease in hepatic TGSH tended to be less in FOVE versus SOVE. Exhaustive exercise also modulated tissue antioxidant enzymes.",
            "output": [
                "Does vitamin E regulate changes in tissue antioxidants induced by fish oil and acute exercise?"
            ]
        },
        {
            "id": "task847-91155c1d5daf4bf986792fe21b9a69dc",
            "input": "Parvovirus B19 has been demonstrated in testes of patients with germ cell tumours but not in controls, raising the possibility that the virus has an aetiological role in these tumours. The aims of this study were to investigate the association of the virus with germ cell tumours and to localise the virus histologically.', 'DNA was extracted from paraffin wax embedded sections of testes from 10 seminomas, eight teratomas, two mixed seminoma/teratomas, and 10 testes showing benign histology. Polymerase chain reaction (PCR) amplification of three regions within the NS and VP1/2 genes was carried out in duplicate on all samples. One PCR positive case (seminoma/teratoma) was examined by microdissection of histologically defined tissue components followed by PCR amplification of parvoviral sequences. Samples from PCR positive patients were immunostained using a B19 specific monoclonal antibody.', 'Seven cases were PCR positive, these comprised two of 10 seminomas, one of two mixed tumours, none of eight teratomas, and four of 10 benign controls. PCR analysis of the material microdissected from the seminoma/teratoma showed the presence of the virus in regions of seminoma, teratoma, intratubular germ cell neoplasia, normal tubules, and connective tissue. All patient samples studied immunohistochemically were negative.",
            "output": [
                "Is parvovirus B19 associated with benign testes as well as testicular germ cell tumours?"
            ]
        },
        {
            "id": "task847-e7051e0b3ca746ad9b8c3933a1eb8569",
            "input": "Genetically modified T-lymphocytes are potential therapeutic agents for the treatment of various disorders. Successful retroviral infection of primary murine T-lymphocytes is a prerequisite to the study of adoptive cell therapies in a small animal model. The definition of factors controlling retroviral infection of T-lymphocytes would also be useful to better understand retroviral diseases. However, retroviral-mediated gene transfer into murine primary T-cells has remained elusive.', 'In order to define the requirements for stable and efficient gene transfer in primary murine T-lymphocytes, we investigated factors capable of affecting retroviral infection. These include activation conditions (using mitogens or monoclonal antibodies), culture conditions (including media composition and cytokine addition), timing of viral exposure, retroviral receptor selection (ecotropic, amphotropic, or vesicular stomatitis virus G (VSV-G) glycoprotein receptor), and viral titer.', 'We show that efficient gene transfer can be achieved in murine T-lymphocytes, provided that a number of favorable conditions are met, in particular optimized T-cell activation conditions, optimal timing of infection, adequate interleukin-2 concentration and T-cell density, and a high viral titer. On a particulate basis, we find that ecotropic particles are more effective than amphotropic or VSV-G-pseudotyped particles, and recommend the use of a specifically selected retroviral packaging cell line. CD4+ T-cells are equally or more infectible than CD8+ lymphocytes, depending on the activation conditions. The Th1 and Th2 subsets are comparably susceptible to retroviral infection, in contrast to what has been reported in some instances of human T-cell infection by human immunodeficiency virus (HIV).",
            "output": [
                "Do activation conditions determine susceptibility of murine primary T-lymphocytes to retroviral infection?"
            ]
        },
        {
            "id": "task847-e110dacceb2c49d699222993b0db3772",
            "input": "The objective was to assess the safety and efficacy of L-NMMA in the treatment of cardiogenic shock.', 'We enrolled 11 consecutive patients with cardiogenic shock that persisted after >24 hours from admission, despite coronary catheterization and primary percutaneous transluminal coronary revascularization, when feasible, and treatment with mechanical ventilation, intraaortic balloon pump (IABP), and high doses of catecholamines. L-NMMA was administered as an IV bolus of 1 mg/kg and continuous drip of 1 mg. kg(-1). h(-1) for 5 hours. Treatment with catecholamines, mechanical ventilation, and IABP was kept constant throughout the study.', 'Within 10 minutes of L-NMMA administration, mean arterial blood pressure (MAP) increased from 76+/-9 to 109+/-22 mm Hg (+43%). Urine output increased within 5 hours from 63+/-25 to 156+/-63 cc/h (+148%). Cardiac index decreased during the steep increase in MAP from 2. 0+/-0.5 to 1.7+/-0.4 L/(min. m(2)) (-15%); however, it gradually increased to 1.85+/-0.4 L/(min. m(2)) after 5 hours. The heart rate and the wedge pressure remained stable. Twenty-four hours after L-NMMA discontinuation, MAP (+36%) and urine output (+189%) remained increased; however, cardiac index returned to pretreatment level. No adverse events were detected. Ten out of eleven patients could be weaned off mechanical ventilation and IABP. Eight patients were discharged from the coronary intensive care unit, and seven (64%) were alive at 1-month follow-up.",
            "output": [
                "Is l-NMMA ( a nitric oxide synthase inhibitor ) effective in the treatment of cardiogenic shock?"
            ]
        },
        {
            "id": "task847-1d3b481cb8cb4d499c004b4e39e81863",
            "input": "Cells of the myeloid lineage comprise a very heterogeneous population with many phenotypes and functional activities including macrophages and dendritic cells. To investigate the status, differentiative potential and lineage commitment of monocytic cells in systemic lupus erythematosus (SLE) patients, this study isolated and cultured peripheral blood monocytes from patients and healthy donors.', 'Monocytes were isolated by gradient centrifugation and adherence to plastic dishes. The cells were then cultured for three days, partially supplemented with GM-CSF and interleukin 4 (IL4) to obtain dendritic cells. The differentiation status was monitored by the expression of surface markers using flow cytometry and cytokine secretion.', 'Monocytes from SLE patients expressed significantly lower numbers of the monocytic marker CD14 and HLA-DR while secreting significantly more tumour necrosis factor alpha (TNFalpha) than monocytes from healthy donors. The addition of GM-CSF and IL4 resulted in an inhibition of TNFalpha secretion, but was not sufficient to generate monocytederived dendritic cells.",
            "output": [
                "Are monocytes from systemic lupus erythematous patients severely altered in phenotype and lineage flexibility?"
            ]
        },
        {
            "id": "task847-70098669aedc400eb6d5557277c526b3",
            "input": "To compare the prevalence of Chlamydia trachomatis infections in ankylosing spondylitis (AS) patients with controls, using DNA amplification assays in urine specimens.', 'The prevalence of C trachomatis infections was assessed in 32 male AS patients and 120 age and sex matched controls. Urine specimens were tested by ligase chain reaction and polymerase chain reaction. In addition, blood samples of AS patients were tested on serum antibodies to C trachomatis (IgA and IgG) by a specific peptide based solid phase enzyme immunoassay. A questionnaire was used to assess the differences in sexual behaviour and ethnic origin between the two groups. AS patients were also asked about disease characteristics.', 'No significant differences were found between cases and controls in the prevalence of C trachomatis infections. No associations were found between C trachomatis antibodies and disease characteristics, except for acute anterior uveitis (AAU). Four of eight (50%) AS men positive for IgG had a history of AAU in comparison with three of 24 (12.5%) IgG negative men (OR = 7.0; 95% confidence intervals: 1.1, 44.1).",
            "output": [
                "Is prevalence of Chlamydia trachomatis in urine of male patients with ankylosing spondylitis increased?"
            ]
        },
        {
            "id": "task847-807effb24afe4b6683ef037149729506",
            "input": "Hypercholesterolemia is associated with abnormal endothelium-dependent vasorelaxation due to decreased nitric oxide bioavailability. Our aim was to examine the effect of adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) to the hypercholesterolemic rabbit carotid artery in vivo. In addition, we examined whether adenovirus-mediated gene transfer was associated with vascular dysfunction.', 'Rabbits were fed a 1% cholesterol diet for 4 weeks followed by a 0.5% cholesterol diet for 6 weeks. Vascular reactivity was assessed in nontransduced carotid arteries from chow- and cholesterol-fed animals. In addition, carotid arteries were surgically isolated, and 2 separate doses of adenoviral vectors encoding eNOS or beta-galactosidase (AdbetaGal) on the contralateral side were delivered to the lumen (1x10(10) and 5x10(10) pfu/mL).', 'Abnormal acetylcholine-mediated endothelium-dependent vasorelaxation was detected in the carotid artery from cholesterol-fed animals, whereas responses to calcium ionophore A23187 and diethylamine NONOate were normal. Vascular reactivity was similar in nontransduced and AdbetaGal-transduced hypercholesterolemic vessels. In vessels transduced with eNOS, transgene expression was demonstrated by immunostaining in both the endothelium and the adventitia and by Western blot analysis. High-dose but not low-dose eNOS gene transfer enhanced endothelium-dependent relaxation in vessels from cholesterol-fed rabbits.",
            "output": [
                "Does in vivo gene transfer of endothelial nitric oxide synthase to carotid arteries from hypercholesterolemic rabbits enhance endothelium-dependent relaxations?"
            ]
        },
        {
            "id": "task847-54372bec1263497faeb105475b1d789f",
            "input": "To determine whether the hemodynamic response to functional stimulation is sensitive to proximal arterial occlusion, we measured the activation flow coupling response in a rat model of acute reversible vascular occlusion.', 'In alpha-chloralose-anesthetized rats (n=18), laser Doppler measurements were made through a thinned skull over the somatosensory cortex in response to electrical forepaw stimulation. Signal-averaged responses to 4 and 8 seconds of electrical forepaw stimulation were obtained before, during, and shortly after acute unilateral or bilateral carotid occlusion produced with the use of a surgically placed snare.', 'Baseline cerebral blood flow was significantly decreased over the forepaw region of the somatosensory cortex after both occlusion of the carotid contralateral to the stimulated forepaw and bilateral occlusion compared with preocclusion (P<0.05). Postocclusion and ipsilateral occlusion led to a nonsignificant increase in baseline cerebral blood flow compared with preocclusion. Contralateral carotid occlusion and bilateral occlusion significantly prolonged the temporal characteristics of the flow response, especially the delay to peak (P<0.05), compared with preocclusion, whereas ipsilateral carotid occlusion significantly shortened the delay to peak (P<0.05). Only contralateral carotid occlusion produced a significant reduction in the peak amplitude of the flow response compared with preocclusion (P<0.05).",
            "output": [
                "Does acute carotid occlusion alter the activation flow coupling response to forepaw stimulation in a rat model?"
            ]
        },
        {
            "id": "task847-9540a1eb3bbb40de9dc58e34f3112922",
            "input": "Although Kupffer cells (KCs) are capable of producing important growth-stimulating cytokines, their role in liver regeneration following partial hepatectomy (PH) remains poorly understood.', 'In the present study liver regeneration was studied after KC-depletion by intravenous administration of liposome-encapsulated dichloromethylene-diphosphonate (C12MDP), a method known to physically eliminate KCs. Furthermore, splenectomy was performed one week prior to PH to exclude the effect of C12MDP-liposomes on macrophage populations in the spleen.', 'KC-depletion was confirmed in cryostat liver sections stained with the monoclonal antibody ED2, a marker for resident tissue macrophages. Forty-eight hours after PH, the cumulative hepatocyte DNA synthesis, as determined in liver sections by the hepatocyte bromodeoxyuridine labeling index, was significantly decreased in KC-depleted rats when compared to control-rats. The weight of the remnant liver, expressed as a percentage of the initial liver weight, was significantly less at 96 h after PH in KC-depleted rats. KC-depletion abolished the hepatic interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA synthesis and decreased hepatic expression of tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF) and transforming growth factor-beta1(TGF-beta1) mRNA after PH, as was assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Moreover, at 4 h after PH the systemic release of IL-6 was significantly decreased in KC-depleted rats.",
            "output": [
                "Does kupffer cell depletion by CI2MDP-liposomes alter hepatic cytokine expression and delays liver regeneration after partial hepatectomy?"
            ]
        },
        {
            "id": "task847-2db83ce9b68c40ecab144bea4b085493",
            "input": "Reflex sympathetic dystrophy (RSD) is, from the onset, characterized by various neurological deficits such as an alteration of sensation and a decrease in muscle strength. We investigated if afferent A-beta fibre-mediated reflexes are changed in lower extremities affected by acute RSD.', 'The involvement of these fibres was determined by analyzing reflex responses from the tibialis anterior (TA) and biceps femoris (BF) muscles after electrical stimulation of the sural nerve. The reflexes were studied during walking on a treadmill to investigate whether the abnormalities in gait of the patients were related either to abnormal amplitudes or deficient phase-dependent modulation of reflexes. In 5 patients with acute RSD of the leg and 5 healthy volunteers these reflex responses were determined during the early and late swing phase of the step cycle.', 'No significant difference was found between the RSD and the volunteers. During early swing the mean amplitude of the facilitatory P2 responses in BF and TA increased as a function of stimulus intensity (1.5, 2 and 2.5 times the perception threshold) in both groups. At end swing the same stimuli induced suppressive responses in TA. This phase-dependent reflex reversal from facilitation in early swing to suppression in late swing occurred equally in both groups.",
            "output": [
                "Are leg muscle reflexes mediated by cutaneous A-beta fibres normal during gait in reflex sympathetic dystrophy?"
            ]
        },
        {
            "id": "task847-38790770eed64d4cb23aa606f12dd859",
            "input": "Gastric mucosal injury by Helicobacter pylori has been suggested to be mediated by various cytokines induced by this organism. Nitric oxide (NO) is an important effector molecule involved in immune regulation and defence. To clarify the mechanisms by which H. pylori induces gastric mucosal cell injury, we examined whether H. pylori induces gastric epithelial death via NO production.', 'Cytotoxic and non-cytotoxic strains of H. pylori were used. The death of MKN45 cells caused by H. pylori was examined by the 3-(4,5-dimethyl-thiazole-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Aminoguanidine was used to inhibit inducible nitric oxide synthase (iNOS) activity. Expression of iNOS mRNA was determined by the reverse transcriptase-polymerase chain reaction and the DNA fragmentation analysis was performed by using agarose gel electrophoresis.', 'The MTT assay revealed that neither viable H. pylori nor other components of the microorganism induced cell death. Both preincubation of MKN45 cells with interferon-gamma for 6 h and coculture with TNF-alpha significantly increased the cytotoxicity of H. pylori. Both cytotoxic and non-cytotoxic strains of H. pylori induced cell death. Expression of iNOS mRNA was observed in MKN45 cells at 6, 8 and 12 h after H. pylori inoculation. The cytotoxicity of H. pylori was inhibited by aminoguanidine and DNA fragmentation analysis showed that H. pylori induced apoptosis.",
            "output": [
                "Does helicobacter pylori induce apoptosis in gastric epithelial cells through inducible nitric oxide?"
            ]
        },
        {
            "id": "task847-77eb0bf19272459e934252cbd7886693",
            "input": "We assessed the expression of natural killer (NK) receptors in recurrent aborters before and after immunotherapy using their husbands' peripheral blood mononuclear cells (PBMCs).\", 'Using stored PBMCs from recurrent aborters before and after the immunotherapy, the expression of NK receptors, CD158a, CD158b, CD159 and CD94, were analyzed using monoclonal antibodies for respective receptors. The diversity of killer activatory receptors (KARs) and killer inhibitory receptors (KIRs) was also examined using reverse transcriptase-polymerase chain reaction (RT-PCR)-single strand conformation polymorphism (SSCP) method.', 'In recurrent aborters, no apparent changes in NK receptor expression and the balance between KARs and KIRs were found before and after the immunotherapy.",
            "output": [
                "Does immunotherapy prevent recurrent abortion without influencing natural killer receptor status?"
            ]
        },
        {
            "id": "task847-c475d0389a50463aadff18bf124c690c",
            "input": "We sought to evaluate whether improvement in ejection fraction (EF) with carvedilol therapy is accompanied by improvement in neurohumoral factors.', 'Forty-two patients with dilated cardiomyopathy were given carvedilol for 3 to 5 months. Changes in EF, plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and norepinephrine levels were determined. Iodine-123 metaiodobenzylguanidine (MIBG) images were also obtained before and after carvedilol therapy. Myocardial uptake of MIBG was calculated as the heart to mediastinal activity ratio (H/M). Storage and release of MIBG was calculated as percent myocardial MIBG washout rate (WR). We divided patients into 2 groups: 27 responders whose EF increased by more than 5% and 15 nonresponders whose EF increased by 5% or less. EF of responders increased by 15 +/- 5% and that of nonresponders by 1 +/- 4%. Although MIBG image-derived indexes of nonresponders remained unchanged, the delayed H/M (1.91 +/- 0.34 v 2.24 +/- 0.53, P < .01) and WR (49 +/- 11 v 39 +/- 9%, P < .01) of responders improved, respectively. The plasma ANP (51 +/- 50 v 27 +/- 24 pg/mL, P < .01) and BNP (194 +/- 197 v 49 +/- 62 pg/mL, P < .01) levels of responders decreased. The degree of changes in the plasma BNP level correlated with changes in EF (r = -.698, P < .01).",
            "output": [
                "Is improvement in left ventricular function in response to carvedilol accompanied by attenuation of neurohumoral activation in patients with dilated cardiomyopathy?"
            ]
        },
        {
            "id": "task847-f92148264d8a4788b925c43c21208869",
            "input": "In vitro biomechanical study using a programmable testing apparatus that replicated physiologic flexion/extension cervical spine motion and loading mechanics.', 'To determine the influence of anterior plating on multilevel cervical strut-graft mechanics in vitro.', 'The addition of anterior instrumentation does not prevent construct failure in multilevel cervical corpectomy.', 'Six fresh human cadaveric cervical spines (C2-T1) were tested in the four following sequential conditions: harvested, C4-C6 corpectomy, strut-grafted, and strut-grafted with an anterior cervical plate. A force-sensing strut-graft was used to measure compression/tension, flexion/extension and lateral bending moments, and axial torsion. Parameters of stiffness, vertebral motion, and strut-graft loads were compared to determine differences between the four spine conditions.', 'Application of the anterior plate significantly increased the global stiffness (P < 0.01) and decreased the local motion (P < or = 0.01) of the instrumented levels (C3-C7). Flexion of the strut-grafted spine loaded the strut-graft, whereas extension unloaded the strut-graft. With the anterior plate, flexion of the plated spine unloaded the strut-graft. Extension significantly loaded the strut-graft more than similar degrees of flexion in the strut-grafted condition (P = 0.01). Strut-graft loading end limits of 225 N were reached with a mean 7.5 degrees extension in the plated spines.",
            "output": [
                "Does anterior cervical plating reverse load transfer through multilevel strut-grafts?"
            ]
        },
        {
            "id": "task847-34ebe0662c724741bc2311427708ddf1",
            "input": "To evaluate magnesium deficiency during and after acute myocardial infarction (AMI) and the role of intravenous magnesium therapy given in the early postinfarction period.', 'One hundred patients with AMI were randomly assigned to 2 equal groups and monitored over a 4-week period. The placebo group received intravenous dextrose solution and the trial group was given 15 g intravenous magnesium (62 mmol) over a 48-hour period. Serum magnesium levels were measured on days 1, 2, 4, and 6 after admission by calorimetry with methyl thymol blue.', 'The groups were comparable in prevalence of risk factors for coronary artery disease and other acute parameters of AMI. The serum magnesium levels of a group of 50 controls were higher (1.61 +/- 0. 21 vs 1.23 +/- 0.27mEq/L) than in patients with AMI (P <.001). There was an increase in serum magnesium levels in the trial group on day 2 (1.73 +/- 0.27 vs 1.29 +/- 0.28 mEq/L; P <.001) as well as on day 4 (1.62 +/- 0.25 vs 1.38 +/- 0.36 mEq/L; P <.001). The trial group also showed significantly lower incidence of arrhythmias (8% vs 34%) and death (4% vs 20%). The mortality rate from pump failure was reduced in the trial group (4% vs 14%).",
            "output": [
                "Is benefits of magnesium in acute myocardial infarction : timing crucial?"
            ]
        },
        {
            "id": "task847-a35b1e3a535f4c97a5fc38e7fc4f3ea2",
            "input": "Considerable interest exists today in biochemical or immunochemical tests for monitoring the progression of osteoarthritis (OA). It has been suggested that measurements made on synovial fluid (SF) will more accurately reflect the magnitude of cartilage destruction in an index joint than those performed on serum. However, we have shown that the synovitis that occurs in OA affects the rate of protein clearance from the joint. We tested the hypothesis that if adjusted for clearance rate, the SF concentration of cartilage proteoglycans (PG) estimates severity of chondropathy and predicts progression of cartilage damage more accurately than if clearance is not taken into account.', 'Clearance of radioiodinated serum albumin (RISA), a surrogate for the clearance of PG, was measured in 19 adult dogs at baseline and again 16 weeks and 32 weeks after anterior cruciate ligament transection (ACLT). Severity of chondropathy was determined arthroscopically after 16 weeks of instability and at postmortem 32 weeks after ACLT.', 'Adjustment for the RISA clearance rate showed that the SF PG concentration markedly underestimated the quantity of PG released from the OA cartilage. Regardless of whether the concentration was adjusted for clearance, no correlation existed between the SF PG level and the severity of chondropathy. Further, the SF concentration of PG 16 weeks after ACLT failed to predict severity of cartilage damage at postmortem.",
            "output": [
                "Does synovial fluid glycosaminoglycan concentration correlate with severity of chondropathy or predict progression of osteoarthritis in a canine cruciate deficiency model?"
            ]
        },
        {
            "id": "task847-10dcd212b2f645bcb2b94433d246a2ee",
            "input": "Prepubertal children and early adolescents with bipolar disorders (PEA-BP) who participate in the ongoing study \"Phenomenology and Course of Pediatric Bipolar Disorders\" have a high prevalence of ultradian (within 24-hour periods) rapid cycling. Based on a case-control finding reported in bipolar (BP) adults of an association between rapid and ultradian rapid cycling with the low-activity allele of catechol-O-methyltransferase (l-COMT), study of linkage and linkage disequilibrium of l-COMT in the PEA-BP population seemed warranted.', \"Genotypes on a subset of the larger PEA-BP sample, for whom trio blood collection was complete (i. e., probands and both of their biological parents), were used to perform transmission disequilibrium tests (TDTs). Diagnoses were established from a comprehensive battery that included WASH-U-KSADS (Washington University Kiddie Schedule for Affective Disorders and Schizophrenia) given to both mothers and children and from consensus conferences. Probands with PEA-BP (N = 52) were 10.9 +/- 2.8 years old at index episode; had a mean age of BP onset at 8.0 +/- 3.8 years; were severely impaired, with a mean Children's Global Assessment Scale score of 44.5 +/- 8.9; and manifested the cardinal features of BP (84.6% had euphoric mood, 76.9% had grandiosity, and 57.7% had psychosis). Ultradian rapid cycling occurred in 75%. Genotyping of the single nucleotide polymorphism at COMT was performed using automated capillary electrophoresis single-strand conformational polymorphism with detection by laser-induced fluorescence.\", 'Transmission disequilibrium tests were not significant for preferential transmission of l-COMT for the ultradian rapid-cycling subgroup or for the entire PEA-BP sample.",
            "output": [
                "Is ultradian rapid cycling in prepubertal and early adolescent bipolarity in transmission disequilibrium with val/met COMT alleles?"
            ]
        },
        {
            "id": "task847-2645c74a92264ca8afee7496949a27c3",
            "input": "To test whether extension of the C-terminus of human chorionic gonadotropin (hCG) alpha-subunit (halpha) alters the bioactivity of the recombined alphabeta heterodimer.', 'The stop codon of halpha was mutated to produce a 24 amino acid extension.', 'The extended halpha (alpha(+24)) was co-expressed with hCGbeta in COS-7 cells and the receptor binding and in vivo bioactivity of the secreted hormone was compared with its wild-type counterpart.', 'This extension did not impair the binding of hCG to rat LH/CG receptors and provoked a sixfold reduction in its stimulatory activity of testosterone secretion in rat Leydig cells.",
            "output": [
                "Does human chorionic gonadotropin with C-elongated alpha-subunit retain full receptor binding and partial agonist activity?"
            ]
        },
        {
            "id": "task847-d0b82f9ef8214ed7b8d922b4b550e975",
            "input": "Mycophenolate mofetil (MMF) is an effective immunosuppressant developed for use in organ transplantation. It specifically targets lymphocyte purine biosynthesis. However, side effects do occur. Understanding how the active metabolite of MMF, mycophenolic acid (MPA) affects the normally integrated interaction between intracellular purine and pyrimidine pathways might aid the development of improved therapeutic regimes.', 'We used a primary human T-lymphocyte model to study how preincubation with MPA (0.1-50 microM) affected normal ribonucleotide pool responses to phytohemagglutinin using radiolabeled precursors.', 'MPA not only restricted the mitogen-induced expansion of GTP pools, but actually induced a severe drop in both GTP (10% of unstimulated cells) and GDP-sugar pools, with a concomitant fall in ATP (up to 50%). These effects were concentration dependent. By contrast, uridine pools expanded whereas CTP pools remained at resting levels. These changes were confirmed by the altered incorporation of [14C]-bicarbonate and [14C]-glycine into nucleotides. Restriction of [14C]-hypoxanthine incorporation and reduction of [14C]-uridine uptake comparable to that of unstimulated cells indicated that MPA also inhibited both salvage routes of nucleotide synthesis.",
            "output": [
                "Does mycophenolic acid-induced GTP depletion also affect ATP and pyrimidine synthesis in mitogen-stimulated primary human T-lymphocytes?"
            ]
        },
        {
            "id": "task847-91eb7250119d494296b8098e008a69d6",
            "input": "It has been reported that T-cell depletion by in vivo treatment with monoclonal antibodies results in polyclonal B-cell activation. However, its effects on B cells responding to Galalpha1,3Gal (Gal) epitopes remain unknown.', 'alpha1,3-Galactosyltransferase-deficient (GalT-/-) mice were treated with depleting anti-CD4 and CD8 monoclonal antibodies. The kinetics of anti-Gal natural antibodies (NAb) and total immunoglobulin levels in their sera were evaluated. The frequencies of anti-Gal NAb-producing cells were determined in the various tissues of GalT-/- mice by enzyme-linked immunospot assay.', 'In vivo T-cell depletion led to significant increases in both anti-Gal IgM and total IgM levels in sera of GalT-/- mice, but did not influence either anti-Gal IgG or total IgG levels. An increased frequency of anti-Gal and total IgM-producing cells was observed in the spleens and bone marrow of T-cell-depleted GalT-/-mice but not in peritoneal cavity cells.",
            "output": [
                "Does in vivo T-cell depletion enhance production of anti-GALalpha1,3GAL natural antibodies in alpha1,3-galactosyltransferase-deficient mice?"
            ]
        },
        {
            "id": "task847-1d3a40c0f609460e97d63ba91112f2a0",
            "input": "To determine the role of lymphocyte proliferation assay of synovial fluid mononuclear cells (SFMC) with whole fraction bacteria in the diagnosis of reactive arthritis (ReA) or arthritis of unknown origin.', 'We stimulated SFMC of 52 unselected patients who consecutively presented in our rheumatology outpatient clinic with the following diagnoses: ReA (n = 8), rheumatoid arthritis (RA) (n = 16), ankylosing spondylitis (AS) (n = 6), osteoarthritis (OA) (n = 5), psoriatic arthritis (PsA) (n = 5) and arthritis of varying origin (AVO) (n = 12) and peripheral blood MC (PBMC) of 10 healthy controls with arthritogenic (Y. entero-colitica, S. enteritidis, C. trachomatis) and non-arthritogenic (E. coli, K. pneumoniae, S. pyogenes, C. albicans) bacteria/mitogens and Tetanus toxoid. T cell proliferation was measured in a standard [3H] Thymidine uptake assay.', 'In all groups of patients tested, SFMC could be stimulated both by arthritogenic and non-arthritogenic bacteria. So-called specific responses were observed in patients with ReA, but also in RA and AS.",
            "output": [
                "Is synovial fluid lymphocyte proliferation in response to crude microbial antigens useful as a diagnostic test to specifically indicate a bacterial cause of arthritis?"
            ]
        },
        {
            "id": "task847-a71d3b34082c44e4838fe9b75d438b74",
            "input": "White cell reduction of blood products minimizes the risks of alloimmunization against HLA-antigens, the transmission of viral diseases and the incidence of platelet transfusion reactions. One modern strategy is leukocyte depletion with an integrated filter system immediately after preparation and prior to storage.', 'We evaluated the efficiency of a novel in-line filter system Sepacell PLX-5 BPS for leukocyte reduction of platelet concentrates (PC) from pooled buffy-coats. A total of 44 PCs were investigated with regard to different filtration flow rates (25-110 ml/min) and leukocyte depletion and thrombocyte recovery rates were analysed. Furthermore, we studied the influence of filtration on PCs over a storage period of 6 days (n = 12) by investigation of pH, lactate and glucose. Platelet function was determined by means of hypotonic shock response, external shape change and expression of CD62p.', 'The mean leukocyte depletion rate was > log 5. After filtration the mean leukocyte count was 0.12 +/- 0.21 x 10(6). In 60% of the PCs the leukocyte count lay below the detection level of the Nageotte chamber, which is < 0.3 x 10(5). The flow rate correlates significantly with the leukocyte count in the PCs (r = 0.325; p = 0.033) and therefore with the leukocyte depletion rate (r = -0.422; p = 0.01). Flow rates under 40 ml lead to a significantly lower leukocyte contamination. Only in one PC, at a flow rate of 84 ml/min, was the leukocyte threshold of 1 x 10(6) exceeded. We did not find a significant correlation between filtration flow rate and thrombocyte recovery (r = 0.315; p = 0.069). The mean platelet count in the PC was 2.88 +/- 0.47 x 10(11). Compared with the thrombocyte count in the pooled buffy coat, the recovery was 68.6%. We observed a decrease of pH, glucose, external shape change and hypotonic shock response over the storage period while lactate and the expression of CD62p increased.",
            "output": [
                "Does the flow rate significantly influence the leukocyte depletion rate during prestorage in-line filtration of platelet concentrates?"
            ]
        },
        {
            "id": "task847-0d2ea182a62d4f33822b7c4687313a23",
            "input": "The number of positive axillary lymph nodes predicts prognosis and is often important in determining adjuvant chemotherapy in breast cancer patients. This study was undertaken to determine if differences in the extent of axillary node dissection would alter the number of reported positive nodes.', \"The study population consisted of 302 patients with invasive breast cancer who underwent complete (level I/II/III) axillary lymph node dissection. Assuming that all patients had undergone a level I/II dissection, it was determined how frequently a patient's nodal category (0, 1-3, 4-9, >10 positive nodes) would have been altered if a level I or level I/II/III dissection were performed.\", 'Assuming that all 302 patients had undergone a level I/II dissection, performing only level I dissection would have resulted in a change in nodal category in 15.9% of all patients and 36.1% of patients with positive nodes. The corresponding changes for a level I/II/III dissection would have been 4.3% and 9.5%, respectively.",
            "output": [
                "Does variation in axillary node dissection influence the degree of nodal involvement in breast cancer patients?"
            ]
        },
        {
            "id": "task847-a585a01db6c84b87a891193c0e641abd",
            "input": "Hypertrophic cardiomyopathy is a myocardial disorder resulting from inherited sarcomeric dysfunction. We report a mutation in the myosin-binding protein-C (MyBP-C) gene, its clinical consequences in a large family, and myocardial tissue findings that may provide insight into the mechanism of disease.', 'History and clinical status (examination, ECG, and echocardiography) were assessed in 49 members of a multigeneration family. Linkage analysis implicated the MyBP-C gene on chromosome 11. Myocardial mRNA, genomic MyBP-C DNA, and the myocardial proteins of patients and healthy relatives were analyzed. A single guanine nucleotide insertion in exon 25 of the MyBP-C gene resulted in the loss of 40 bases in abnormally processed mRNA. A 30-kDa truncation at the C-terminus of the protein was predicted, but a polypeptide of the expected size ( approximately 95 kDa) was not detected by immunoblot testing. The disease phenotype in this family was characterized in detail: only 10 of 27 gene carriers fulfilled diagnostic criteria. Five carriers showed borderline hypertrophic cardiomyopathy, and 12 carriers were asymptomatic, with normal ECG and echocardiograms. The age of onset in symptomatic patients was late (29 to 68 years). In 2 patients, outflow obstruction required surgery. Two family members experienced premature sudden cardiac death, but survival at 50 years was 95%.",
            "output": [
                "Is a newly created splice donor site in exon 25 of the MyBP-C gene responsible for inherited hypertrophic cardiomyopathy with incomplete disease penetrance?"
            ]
        },
        {
            "id": "task847-59824a524a7e458abc27b80de0e7d223",
            "input": "Unintentional injuries are the leading cause of death in children, and falls are the most common type of unintentional injury in the US. The incidence of falls from windows, a common cause of death in urban areas, has not been described outside major cities such as New York and Chicago, and rates in urban and suburban areas have not been compared.', 'To estimate the incidence and identify the population at risk for falls from windows among children in Hamilton County, Ohio.', \"Retrospective case series identified using Cincinnati Children's Hospital Medical Center (CHMC) Trauma Registry.\", 'Hamilton County, Ohio, which has urban and nonurban areas.', 'Children less than 15 years old residing in Hamilton County, Ohio, presenting to CHMC in Cincinnati, Ohio, after a fall from a window between January 1, 1991, and December 31, 1997.', 'Annual incidence by age, race, gender, and residence of those who fell from windows.', 'Over the 7-year study period, 86 (6.3%) of 1,363 falls were from windows. The mortality rate for falls from windows was 4.7%, compared to 0.07% for all other falls presenting to CHMC (P<.0001). Children 0-4 years old had a higher rate of falls than children aged 5-14 (14.6/100,000 vs. 2.0/100,000) (P<.0001). Males were twice as likely to fall as females (P<.016), and black children were three times more likely to fall than non-black children (P<.002). The incidence of falls in the city of Cincinnati was four times that of the non-urban area (P<.0002).",
            "output": [
                "Does childhood injuries and deaths due to fall from windows?"
            ]
        },
        {
            "id": "task847-5e52f8ceaa59436cb6c66a01cbfba877",
            "input": "Hypoxemia is a common complication of chronic obstructive pulmonary disease and a major factor in patients' prognosis and quality of life. The response to exercise has been evaluated by various means but no standardization has been accepted.\", 'To suggest a simple outpatient technique for evaluating the response of arterial oxygen saturation to exercise for use as a marker of disease severity.', 'Ninety-six patients with various degrees of COPD were divided into three groups: mild (forced expiratory volume in 1 sec > 65%), moderate (FEV1 between 50 and 65%), and severe (FEV1 < 50%). Using continuous oximeter recording we measured oxygen saturation during 15 steps of climbing, and quantified oxygen desaturation by measuring the \"desaturation area,\" defined as the area under the curve of oxygen saturation from the beginning of exercise through the lowest desaturation point and until after recovery to the baseline level of oxygen percent saturation. Desaturation was correlated to spirometry, lung gas volumes, blood gas analysis, and 6 min walking distance.', 'A good correlation was found between severity of COPD and baseline SaO2, lowest SaO2, recovery time, and desaturation area. A negative correlation was found between desaturation area and FEV1 (r = -0.65), FEV1/forced vital capacity (r = -0.58), residual volume to total lung capacity (r = 0.52), and diffusing lung capacity for carbon monoxide (r = -0.52). In stepwise multiple regression analysis only FEV1 correlated significantly to desaturation area. A good correlation was noted between 6 min walking distance and desaturation area with the 15 steps technique (r = 0.56).",
            "output": [
                "Do quantitative 15 steps exercise oximetry as a marker of disease severity in patients with chronic obstructive pulmonary disease?"
            ]
        },
        {
            "id": "task847-63561275a2f14e4b837a350951021f9b",
            "input": "Both in experimental colitis and in inflammatory bowel disease, colonic eicosanoid generation is enhanced and may contribute to the pathogenesis of the inflammatory response.', 'To evaluate the effect of selective cyclo-oxygenase-2 (COX-2) inhibitors on the extent and severity of two models of experimental colitis.', 'Colitis was induced by intra-caecal administration of 2 ml 5% acetic acid or intra-colonic administration of 0.1 ml 3% iodoacetamide. Rats were treated intra-gastrically with nimesulide 2 x 10 mg/kg/day, or once with SC-236 6 mg/kg, and killed 1 or 3 days after damage induction. The colon was isolated, weighed, macroscopic damage was measured, and mucosal samples were obtained for histology and for determination of myeloperoxidase (MPO) and nitric oxide synthase (NOS) activities and eicosanoid generation. The serum levels of thromboxane B2 (TXB2), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined.', 'Nimesulide significantly decreased the extent of colitis induced by acetic acid. Both nimesulide and SC-236 significantly decreased the extent of iodoacetamide-induced colonic damage. The decrease in the extent of colitis induced by nimesulide was accompanied by a significant decrease in mucosal MPO and NOS activities. Nimesulide and SC-236 decreased the enhanced colonic eicosanoid generation in acetic acid and iodoacetamide-induced colitis, and, in iodoacetamide-treated rats, nimesulide also decreased the elevated serum TNF-alpha and IL-1beta levels.",
            "output": [
                "Do cyclo-oxygenase-2 inhibitors ameliorate the severity of experimental colitis in rats?"
            ]
        },
        {
            "id": "task847-2605675c5c8f4a70853f166db3bef03c",
            "input": "Although the majority of evidence does not support association between Helicobacter pylori infection and ischaemic heart disease, the nature of this relationship may differ when virulence of the infecting strains are examined.', 'The prevalence of IgG antibody evidence of infection with CagA positive stains of H. pylori was investigated in stored plasma samples from 259 cases of myocardial infarction (aged 25-70 years, 74 males) and 259 population based controls from the same area in Northern Ireland. Two-hundred and seventy (52.1%) subjects were seropositive for anti-CagA IgG. CagA seropositivity was more common in cases than in controls: 56.4 vs 47.9%, odds ratio for seropositivity in cases (95% CI) 1.41 (1.00, 1.99). Substantial attenuation of this relationship occurred on adjustment for age, sex, number of siblings, smoking and measures of socio-economic status: odds ratio (95% CI) 1.16 (0.79, 1.70). A similar pattern was seen for seropositivity for all H. pylori strains.",
            "output": [
                "Is infection with virulent strains of Helicobacter pylori associated with ischaemic heart disease : evidence from a population-based case-control study of myocardial infarction?"
            ]
        },
        {
            "id": "task847-cd3bb8c871434f59919aefc83e6c4cd6",
            "input": "The potential to modulate the inflammatory response has renewed interest in hypertonic saline (HTS) resuscitation of injured patients. However, the effect of the timing of HTS treatment with respect to polymorphonuclear neutrophil (PMN) priming and activation remains unexplored. We hypothesized that HTS attenuation of PMN functions requires HTS exposure before priming and activation.', 'Isolated PMN were incubated in HTS (180 mM Na+) before L-alpha-phosphatidylcholine, beta-acetyl-gamma-O-alkyl (PAF)/N-formylmethionyl-leucyl-phenylalanine (fMLP) priming/activation, after priming, or after priming/activation. Superoxide production was measured by the reduction cytochrome c, elastase release by cleavage of AAPV-pNA, and beta2-integrin expression by flow cytometry.', 'HTS before priming or activation decreased beta2-integrin expression, superoxide production, and elastase release. In contrast, HTS after priming/activation augmented superoxide production and elastase release.",
            "output": [
                "Is hypertonic saline attenuation of polymorphonuclear neutrophil cytotoxicity : timing everything?"
            ]
        },
        {
            "id": "task847-f1901de0f9b94cb498316715e91b6e04",
            "input": "To determine whether early enteral feeding in a septic intensive care unit (ICU) population, using a formula supplemented with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), improves clinical outcomes, when compared with a common use, high protein enteral feed without these nutrients.', 'A prospective, randomized, multicentered trial.', 'ICUs of six hospitals in Spain.', 'One hundred eighty-one septic patients (122 males, 59 females) presenting for enteral nutrition in an ICU.', 'Septic ICU patients with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of > or =10 received either an enteral feed enriched with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), or a common use, high protein control feed (Precitene Hiperproteico).', 'One hundred seventy-six (89 Impact patients, 87 control subjects) were eligible for intention-to-treat analysis. The mortality rate was reduced for the treatment group compared with the control group (17 of 89 vs. 28 of 87; p < .05). Bacteremias were reduced in the treatment group (7 of 89 vs. 19 of 87; p = .01) as well as the number of patients with more than one nosocomial infection (5 of 89 vs. 17 of 87; p = .01). The benefit in mortality rate for the treatment group was more pronounced for patients with APACHE II scores between 10 and 15 (1 of 26 vs. 8 of 29; p = .02).",
            "output": [
                "Does an immune-enhancing enteral diet reduce mortality rate and episodes of bacteremia in septic intensive care unit patients?"
            ]
        },
        {
            "id": "task847-f772aa0eae804c59b71144569ee20830",
            "input": "Are the results of cemented titanium hip arthroplasty as bad as described in literature? We present the 10-year results of a cemented mild grid blasted Titanium-Aluminium-Vanadium Stem in Total-Hip-Arthroplasty.', 'The clinical and radiological reexamination was documented in standardized questionnaire in which several scores were integrated. All X-rays were stored and analysed by a special hardware and software computer system.', \"35% of all patients could be reexamined both clinically and roentgenologically. 71 patients were male (mean age 56.1 years) and 130 female (mean age 59.3 years). The average follow-up period was 11 years and 4 months. The mean Merle d'Aubign\u00e9 hip score increased from 10.5 to 16.0 points at the follow-up evaluation. Radiolucent lines were according to the zones of Gruen seen in 1% to 22% depending on the zone and the size of the femoral component. 18 reoperations of the femoral component (2.9%) had to be performed. The survivorship analysis (Kaplan-Meier) showed a 95.4% survival of the femoral component after 10 years.",
            "output": [
                "Does [ 10 year result with a cemented fine-grit-blasted titanium-aluminum-vanadium hip endoprosthesis shaft ]?"
            ]
        },
        {
            "id": "task847-60916baa9acf4d8e927fc024325269bf",
            "input": "An early sign of apoptosis in many cells is the appearance of phosphatidylserine (PS) on the outside of the plasma membrane, whilst the cells still retain the ability to exclude DNA-binding molecules such as propidium iodide and 7-aminoactinomycin D (7-AAD). The protein annexin V binds preferentially to PS and has often been used to monitor the early phase of apoptosis. There have been some conflicting results concerning whether annexin V binds to camptothecin (CAM)-treated HL-60 cells, a commonly used model for apoptosis. We investigated the effects of culturing HL-60 cells for up to 8 h with a range of CAM concentrations.', 'We used flow cytometry to measure cellular light scatter, annexin V-FITC binding, and 7-AAD uptake, and DNA content after fixation and permeabilization. We also used microscopy to examine the morphology of cells (both unsorted and sorted according to their light scatter) after cytocentrifugation.', 'We found that CAM caused the rapid appearance of low light scatter apoptotic bodies. Even among cells with \"normal\" light scatter, there was widespread DNA cleavage and nuclear fragmentation by 3 h. The percentage of apoptotic bodies peaked at about 4 h and it was only afterward that annexin V binding could be detected to both intact cells and to apoptotic bodies. When they first appeared, the intact annexin V+ cells had S-phase DNA content.",
            "output": [
                "Is there substantial nuclear and cellular disintegration before detectable phosphatidylserine exposure during the camptothecin-induced apoptosis of HL-60 cells?"
            ]
        },
        {
            "id": "task847-3814dd3973674557be4187911d891b12",
            "input": "The transcription factor nuclear factor-kappaB (NF-kappaB) plays a central role in regulating immune and inflammatory responses. Because butyrate deficiency has been associated with inflammatory bowel disease, we examined the effect of butyrate on NF-kappaB activity in the human HT-29 colonic cell line.', 'The influence of butyrate (4 mmol/L) on NF-kappaB activity was determined using the gel mobility shift assay. The effect of butyrate on the expression of NF-kappaB subunits and inhibitory proteins was determined by immunoblotting. NF-kappaB-regulated gene expression was assayed by primer extension of intercellular adhesion molecule 1 and Mn superoxide dismutase messenger RNA, and by analysis of a transfected luciferase reporter.', 'Exposure of HT-29 cells to butyrate eliminated their constitutive NF-kappaB, p50 dimer activity. This inhibition corresponded with a reduction in p50 nuclear localization, without a reduction in expression. Butyrate also selectively modulated activation of NF-kappaB, suppressing its activation by tumor necrosis factor alpha and phorbol ester more than 10-fold, without affecting the activity induced by interleukin (IL)-1beta. Butyrate did, however, enhance formation of the stronger p65-p50 transcriptional activator in IL-1beta-stimulated cells. The changes in NF-kappaB activation did not correlate with changes in IkappaBalpha levels. Gene expression reflected DNA binding. The influence of butyrate on NF-kappaB may result in part from its ability to inhibit deacetylases because the specific deacetylase inhibitor trichostatin A has a similar effect.",
            "output": [
                "Does the luminal short-chain fatty acid butyrate modulate NF-kappaB activity in a human colonic epithelial cell line?"
            ]
        },
        {
            "id": "task847-32e0fc1299614090a2d4340a487a41bf",
            "input": "Parenteral control of gastric acid hypersecretion in conditions such as Zollinger-Ellison syndrome (ZES) or idiopathic gastric acid hypersecretion is necessary perioperatively or when oral medications cannot be taken for other reasons (e.g., during chemotherapy, acute upper gastrointestinal bleeding, or in intensive care unit settings).', 'We evaluated the efficacy and safety of 15-minute infusions of the proton pump inhibitor pantoprazole (80-120 mg every 8-12 hours) in controlling acid output for up to 7 days. Effective control was defined as acid output >10 milliequivalents per hour (mEq/h) (<5 mEq/h in patients with prior acid-reducing surgery) for 24 hours.', 'The 21 patients enrolled had a mean age of 51.9 years (range, 29-75) and a mean disease duration of 8.1 years (range, <0.5-21); 13 were male, 7 had multiple endocrine neoplasia syndrome type I, 4 had undergone acid-reducing surgery, 2 had received chemotherapy, and 13 had undergone gastrinoma resections without cure. Basal acid output (mean +/- SD) was 40.2 +/- 27.9 mEq/h (range, 11.2-117.9). In all patients, acid output was controlled within the first hour (mean onset of effective control, 41 minutes) after an initial 80-mg intravenous pantoprazole dose. Pantoprazole, 80 mg every 12 hours, was effective in 17 of 21 patients (81%) for up to 7 days. Four patients required upward dose titration, 2 required 120 mg pantoprazole every 12 hours, and 2 required 80 mg every 8 hours. At study end, acid output remained controlled for 6 hours beyond the next expected dose in 71% of patients (n = 15); mean acid output increased to 4.0 mEq/h (range, 0-9.7). No serious or unexpected adverse events were observed.",
            "output": [
                "Does intravenous pantoprazole rapidly control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome?"
            ]
        },
        {
            "id": "task847-edd26f86237d4d43a8577ff956092941",
            "input": "Analogous to vascular endothelium, bronchial epithelium modulates bronchomotor activity by releasing epithelium-derived relaxing factors. Cardiopulmonary bypass (CPB) is associated with endothelial dysfunction. We examined whether CPB may be associated with bronchiolar epithelial dysfunction in pigs. Pigs were exposed to normothermic CPB for 1.5 h and then separated from CPB. Lung tissues were biopsied before and 30 min after CPB. For time control, lung tissues were biopsied at baseline and after 2 hr of anesthesia. Bronchioles measuring about 100 microm were dissected, and the epithelium was either left intact or denuded. Each bronchiolar segment was preconstricted with 10 microM 5-hydroxytryptamine and relaxation responses to nitroprusside 10(-9)-10(-4) M, isoproterenol 10(-9)-10(-4) M, or the inhaled anesthetics halothane or isoflurane 0-2.5 minimum alveolar anesthetic concentration were examined in vitro by videomicroscopy. Bronchiolar segments demonstrated concentration-dependent relaxation responses to each of the dilators examined. Epithelial denudation reduced bronchodilation to isoproterenol, isoflurane, and halothane, but not to nitroprusside. Bronchodilation was not significantly affected by CPB. We conclude that, unlike vascular endothelial function, porcine bronchiolar epithelium-modulated bronchomotor activity is not significantly affected by normothermic CPB.",
            "output": [
                "Is epithelium-dependent bronchodilatory activity preserved in pig bronchioles after normothermic cardiopulmonary bypass?"
            ]
        },
        {
            "id": "task847-4e7ceef908fe4309b6757f2eac9695fc",
            "input": "Mark/recapture (or capture-recapture) is a simple technique commonly applied to estimate the hypothetical total (including undercount) in a register composed of cases from two or more independent and separately incomplete case lists. This paper seeks to illustrate serious drawbacks in the use of the mark/recapture technique when applied to injuries.', 'Northumbrian children under 15 years of age who were seriously injured in motor vehicle accidents (MVAs) over a five year period ascertained from two data sources: police reports and hospital inpatient records.', 'Individuals (n) appearing in both police (S) and hospital (H) case lists are identified using various matching criteria. The separate and combined influence of age, sex, and casualty class (cyclist, passengers, pedestrians) on the probability of such matching is estimated using multivariate techniques. The hypothetical total incidence of child MVA victims (N) is calculated from N = (S x H)/n.', 'Estimates of the incidences of \"serious\" injuries in MVAs under various conditions of stratification and matching. The overall procedure is tested for conformity with accepted criteria for valid use of mark/recapture.', 'About one third of the 1009 police and 836 hospital records could be exactly matched. There were significant variations in matching proportions by class of accident (pedestrian v passenger v cyclist). This selective recapture or \"heterogeneity\" was not affected by sex, but was independently influenced by the age of the child. Further uncertainty was introduced when matching criteria were slightly relaxed. Estimates of the total population of children with serious injuries vary accordingly from 1729 to 2743. A number of plausible reasons why these two data sources might not be unbiased or mutually independent samples of the total target population are proposed as explanations for this heterogeneity.",
            "output": [
                "Are children goldfish -- mark/recapture techniques and their application to injury data?"
            ]
        },
        {
            "id": "task847-6da649a2c5b847f2b0d5241c6bac6208",
            "input": "The purpose of this study was to compare the arterial response following implantation of a stainless-steel, balloon-expandable, tubular slotted stent with that of a novel computer-designed, multi-cellular stent in normal porcine coronary arteries.', 'Intracoronary stent placement has evolved into the primary strategy for percutaneous revascularization of symptomatic coronary arterial lesions. Presently there is intense interest in developing new stent designs to improve stent delivery and biocompatability.', 'Computer-assisted design was utilized to develop a balloon-expandable stent with symmetric expansion properties, uniform arterial wall coverage, longitudinal flexibility and radial strength. Quantitative coronary angiography and histological assessment of the stented arteries was used to evaluate the acute and chronic vascular responses to a stainless-steel, balloon-expandable, tubular slotted stent as compared to the computer-designed BX stent in the normolipemic swine.', 'Forty stents (24 BX, 16 tubular slotted) were implanted in 19 miniature swine at a mean inflation pressure of 9 atm using identical delivery systems. Eight of the BX and none of the tubular slotted stents were post-dilated with a non-compliant balloon at 12-14 atm. The mean stent-to-artery ratio was similar for the BX (1.03 +/- 0.06) and tubular slotted (1.04 +/- 0.11; p = 0.59) designs. Protrusion or asymmetric radial flaring of a strut at the stent margin was present in 1 of 23 BX stents (4.3%) and 10 of 15 tubular slotted stents (66.7%; p < 0.0001). The mean arterial injury score was significantly less for the BX stent (0.2 +/- 0.2) as compared with the tubular slotted stents (0.4 +/- 0.4; p = 0.025). At 3 days, thrombus area was similar for the BX and tubular slotted designs (0.42 +/- 0.16 mm2 versus 0.44 +/- 0.18 mm2, respectively; p = 0.88). The mean neointimal area was significantly less for the BX at 2 months (1.09 +/- 0.25 mm2 versus 2.93 +/- 2.26 mm2 in the tubular slotted stent) and at 6 months (1.10 +/- 0.26 mm2 versus 2.07 +/- 0.65 mm2 in the tubular slotted stent; p = 0.01), resulting in approximately 50% less in-stent stenosis.",
            "output": [
                "Does stent design favorably influence the vascular response in normal porcine coronary arteries?"
            ]
        },
        {
            "id": "task847-1e556765f36d41be9d8dbd821f26fde1",
            "input": "The stress electrocardiogram (sECG) is routinely used to screen individuals for underlying cardiac pathology before an exercise programme is prescribed. The underlying assumption is that the cardiac responses elicited during the sECG test are similar to those achieved during participation in sporting activities. However, this premise may be incorrect since the physical demands of different modes of exercise vary substantially.', \"Ten veteran league squash players (LSP), 10 social squash players (SSP), 10 league runners (LR), 10 social runners (SR) and 10 sedentary individuals (SED) were recruited for the study. All subjects completed a lifestyle questionnaire, a full medical examination and a routine sECG. Thereafter each subject's heart rate (HR) was monitored on two separate occasions while participating in sporting activity.\", 'No sECG exercise-induced abnormalities were observed, although five subjects showed resting abnormalities. Maximal HR during the sECG, and maximal and mean HR during the field tests, were not significantly different between groups. However, maximal HR was significantly higher in all groups during their sporting activities than during stress testing in the laboratory (P < 0.01).",
            "output": [
                "Do veteran athletes exercise at higher maximum heart rates than are achieved during standard exercise ( stress ) testing?"
            ]
        },
        {
            "id": "task847-5bcb1c0f056844229223e72b8c1e1ea7",
            "input": "Lymphopenia has been described in patients with chronic renal failure (CRF). It is postulated that the decline in lymphocytes is due to accelerated apoptosis. We investigated whether dysregulation of programmed cell death plays a role in the immunodeficiency described in CRF.', 'Peripheral blood lymphocytes (PBL) from pre-dialysis uraemic patients (nHD) and haemodialysed patients (HD) were cultured with no stimulus for 96 h. Apoptosis of lymphocytes was measured by propidium iodide staining and flow cytometry. Expression of Fas and Bcl-2 was also analysed by flow cytometry.', 'Peripheral blood B cells were significantly lower in pre-dialysis and haemodialysis uraemic patients compared to control. Lymphocytes from both groups of patients had a higher rate of apoptosis in vitro than those from healthy controls. This effect was more pronounced in B lymphocytes and a significant correlation between the B lymphopenia and the percentage of apoptotic B cells after 48 h of culture without stimulus was observed. The increased lymphocyte apoptosis in CRF was accompanied by a significantly lower in vitro Bcl-2 expression. However, Fas did not seem to play a role in spontaneous lymphocyte apoptosis in end-stage renal disease.",
            "output": [
                "Is b lymphopenia in uremia related to an accelerated in vitro apoptosis and dysregulation of Bcl-2?"
            ]
        },
        {
            "id": "task847-17c39a5b1a3343058f23fbef419f2cc8",
            "input": "During real-time monitoring of the ultrafiltration coefficient (Kuf) in haemodiafiltration (HDF), it was noticed that the ultrafiltration performance of polysulphone membrane dialysers increased when hypertonic glucose (D50%) was administered through the venous blood return.', 'This observation was explored in six non-diabetic chronic dialysis patients during 48 HDF sessions using 1.8 m(2) polysulphone membrane dialysers. In all six patients, 24 sessions were performed with glucose supplementation (as a continuous D50% (500 g/l) infusion at 40 ml/h) and 24 sessions without supplementation.', 'Glucose supplementation led to a marked increase in Kuf from 22.8+/-2.2 (without D50%, n=24) to 32. 1+/-3.9 ml/h/mmHg (with D50%, n=24) (P<0.0001). An increase in percentage reduction ratios for urea and creatinine were also consistently observed during the sessions with glucose administration (from respective mean values of 75+/-5 and 68+/-4% to 79+/-4 and 74+/-10%). Mean double-pool Kt/V, calculated from serum urea concentrations, rose from 1.65+/-0.24 (n=24) to 1.86+/-0.24 (n=24) (P<0.005). Similar results were observed in a subgroup of 18 HDF sessions (nine with glucose and nine without) monitored with an on-line urea sensor of spent dialysate. No detrimental effects were induced at any time.",
            "output": [
                "Does intradialytic glucose infusion increase polysulphone membrane permeability and post-dilutional haemodiafiltration performances?"
            ]
        },
        {
            "id": "task847-b5a34be0890747cea45eb964bb776fc3",
            "input": "Smooth muscle cell (SMC) migration and proliferation are the key steps in the development of atherosclerosis and restenosis. Matricellular proteins have been implicated in cell adhesion, migration and proliferation. Here we investigated the role of the matricellular protein galectin-1 (Gal-1), a beta-galactoside-binding lectin, in SMC proliferation in atheroma and DNA synthesis in cell culture.', 'Protein expression was visualised by tissue section immunostaining. RNA expression was analysed using Northern blot analysis. DNA synthesis of human vascular SMCs was determined by 3H-thymidine incorporation. Recombinant glutathione S-transferase-galectin-1 fusion protein (Gal FP) binding to extracellular matrix (ECM) proteins was measured by ELISA. Gal-1 binding to cells and ECM was estimated using 125I-labelled Gal FP.', 'Prominent Gal-1 staining coincided with SMC proliferation in human coronary endarterectomy samples in organoid culture. In cell culture, Gal-1 mRNA was upregulated in growing SMCs. Gal FP increased serum-induced DNA synthesis of human SMCs on plastic or endogenous ECM, but not of a rat PAC1 SM cell line. Also, Gal FP slightly increased SMC adhesion to ECM. SMCs exhibited a complex pattern of receptor-ligand interactions with Gal FP. The Gal-1 binding to SMCs was much stronger than to ECM, produced by these SMCs. We identified new ECM proteins: thrombospondin, vitronectin and osteopontin, which bound to Gal FP in a dose- and beta-galactoside-dependent manner in ELISA.",
            "output": [
                "Is galectin 1 involved in vascular smooth muscle cell proliferation?"
            ]
        },
        {
            "id": "task847-4af99dccf12d4348857b724e03fda10e",
            "input": "Enterovirus infections are major etiological factors in myocarditis and dilated cardiomyopathy. Using an experimental murine model of this disease, previous studies have shown that myocarditis susceptibility depends upon activation of T lymphocytes expressing the gamma delta T cell receptor (TcR), and that only mouse strains which accumulate gamma delta T cells in the myocardium show apoptosis of myocytes or evidence of dilated cardiomyopathy-like disease. The objective of the present studies is to demonstrate that gamma delta T cells directly induce greater Fas-dependent apoptosis of cultured myocytes than T cells expressing the alpha beta TcR.', 'Bl.Tg.E alpha mice were infected for 7 days with coxsackievirus B3 (CVB3). Hearts were removed and were either formalin-fixed, sectioned and stained with hematoxylin and eosin for inflammation, and using TdT-TUNEL for apoptosis, or were minced and collagenase digested for isolation of gamma delta+ and alpha beta+ T cells using immunomagnetic bead separation. Neonatal cultures of cardiac myocytes were isolated from mice less than 2 days old by collagenase and pancreatin digestion, and were either untreated or infected with virus. Levels of Fas (CD95) were measured using FITC-conjugated hamster anti-mouse Fas monoclonal antibody and flow cytometry. Susceptibility of myocytes to Fas-dependent killing was measured by 51Cr-release by labeled myocytes incubated for 4 h on either 3T3-mock or 3T3-FasL transfected cell monolayers. Killing by T cells was also measured in a 4 h 51Cr-release assay. Fas-dependent and perforin-dependent cytotoxicity was determined by specific blocking using either Fas-Fc or concanamycin A.', 'Virally infected myocyte cultures showed significantly enhanced Fas expression compared to uninfected cells, with maximal upregulation of Fas occurring 18-24 h after virus infection. Both infected and uninfected myocytes were selectively killed by FasL-transfected 3T3 cells but not by mock control cells. Approximately 38% of CD3+ lymphocytes isolated from the heart express the gamma delta TcR with the remainder expressing the alpha beta TcR. Both gamma delta+ and alpha beta+ T cells lysed myocyte targets. Blocking studies indicate that gamma delta+ T cells induced predominantly Fas-mediated killing, while alpha beta+ cell produced more perforin-mediated death, although these effectors were capable of Fas-dependent killing as well.",
            "output": [
                "Do t cells expressing the gamma delta T cell receptor induce apoptosis in cardiac myocytes?"
            ]
        },
        {
            "id": "task847-1484459349c64e19be10039a54239fb1",
            "input": "The Boston HAPPENS (HIV Adolescent Provider and Peer Education Network for Services) program is a collaborative network of care made up of 8 organizations that serve youth and provide coordinated care for human immunodeficiency virus (HIV)-positive, homeless, and at-risk youth aged 12 to 24 years. Learning youth perceptions about the program is essential to determine if the program is meeting their needs.', 'In this qualitative evaluation, 18 youth served by the network met in 4 focus groups to provide their view of the program. Services within 5 categories were assessed: (a) medical care, (b) mental health and substance abuse care, (c) HIV prevention and care, (d) case management, and (e) allocation of finances.', 'Boston HAPPENS has achieved name recognition and provides many needed services for youth from a wide variety of backgrounds. The youth were comfortable receiving care and were appreciative of the comprehensive services available. They provided suggestions for how mental health services could be offered as one-on-one counseling as part of \"wellness care.\" Young participants also requested more recreational and support opportunities for young people living with HIV.",
            "output": [
                "Does youth perceptions of comprehensive adolescent health services through the Boston happen program?"
            ]
        },
        {
            "id": "task847-2da8b8e180ce4d5f898a931b1193babb",
            "input": "A number of risk factors for chronic renal allograft rejection have been identified; in particular the number and severity of acute rejections, hypertension, hyperlipidemia, and insufficient immunosuppression.', 'In a retrospective case control study, all histologically confirmed cases of chronic rejection (n=45) that occurred between 1985 and 1993 among patients transplanted at Huddinge Hospital were compared with twice as many controls. Determinants such as donor age and sex, HLA-mismatch, cold ischemia time, recipient age and sex, body mass index, cause of renal disease, time undergoing dialysis, condition of blood vessels at surgery, time of onset, number of acute rejection episodes during the first 3 months, area under the serum creatinine versus time curve (AUC(Creatinine)), blood pressure, blood lipids, and cyclosporine concentrations at various times after the transplantation were also compared. Additional data were obtained from a questionnaire, concerning 79% of the cases and controls.', 'Cases and controls were similar with regard to most determinants, that is, blood pressure, blood lipids, and average cyclosporine concentrations. The main outstanding risk factor for chronic rejection was the time-averaged creatinine (AUC(Creatinine)) value between day 22 and 3 months after transplantation. The adjusted odds ratio for chronic rejection increased stepwise from 1.1 to 9.2, when AUC(Creatinine) increased from < 150 to >300 micromol/l. The number of acute rejection episodes and number of HLA-mismatches also had a significant effect on the risk of chronic rejection.",
            "output": [
                "Is area under the serum creatinine time-curve a strong predictor of chronic renal allograft rejection?"
            ]
        },
        {
            "id": "task847-b8306da836aa45e79b0d3c4751ff47d5",
            "input": "Increased expression of chemokine mRNA is observed in allogeneic but not syngeneic skin grafts 3-4 days after transplantation. The recipient cells mediating this early inflammatory response in allografts remain unidentified.', 'Isogeneic and allogeneic skin grafts were transplanted to euthymic and athymic nude mice. mRNA expression and protein production of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and the murine homolog of Gro(alpha), i.e. KC, from graft homogenates retrieved 3-4 days posttransplantation was tested by Northern blot hybridization and ELISA. To deplete NK cells, recipients were treated with antiasialo GM1 (ASGM1) antisera or with anti-NK1.1 mAb before transplantation.', 'Expression of KC, MIP-1alpha, and MIP-1beta mRNA was equivalent in C57BL/6 allogeneic skin grafts and BALB/c isografts at day 2 posttransplant. At day 3 posttransplant, chemokine mRNA levels decreased in isografts but were maintained at high levels in the allografts. Increased early chemokine mRNA was also observed in C57BL/6, but not BALB/c++ grafts on BALB/c athymi(nu/nu) recipients. Treatment of allograft recipients with ASGM1 or with anti-NK1.1 antibody eliminated NK cells from the spleen and allograft infiltrating cell populations and decreased early chemokine mRNA levels in allografts 60-70%. Analyses of allograft homogenates indicated increased levels of KC, MIP-1alpha, and MIP-1beta protein at day 4 posttransplant that were decreased in recipients depleted of NK cells. Early chemokine mRNA levels were equivalent in isogeneic and semiallogeneic F1 grafts.",
            "output": [
                "Is early increased chemokine expression and production in murine allogeneic skin grafts mediated by natural killer cells?"
            ]
        },
        {
            "id": "task847-268b716f48544c37ae3bf6abb65544fb",
            "input": "The boundary lubricating ability of human synovial fluid has been attributed to lubricin, a mucinous glycoprotein. We investigated the primary structure of lubricin and its cellular origin.', 'Lubricin was purified from pooled synovial fluid aliquots with normal lubricating activity obtained from patients with osteoarthritis. Lubricating ability of lubricin was assayed in a friction apparatus that oscillates natural latex against a ring of polished glass. Native and lubricin deglycosylated with O-glycosidase DS and NANase III were trypsinized and sequenced by liquid chromatography mass spectrometry. Sequence results were compared to known structures in GenBank. Sequence data from strong matches were used in creating cDNA primers for reverse transcription-polymerase chain reaction (RT-PCR) with RNA from human synovial fibroblasts obtained intraoperatively.', 'Purified lubricin possesses an apparent molecular weight of 280 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Deglycosylation decreased the apparent molecular weight on SDS-PAGE to 120 kDa. Sequences specific for megakaryocyte stimulating factor precursor (MSF) were identified in GenBank. A 100% match was observed for exons 6 though 9 of MSF. Lubricin/MSF reduced the coefficient of friction (m) in the latex:glass bearing from 0.131 to 0.047. MSF is 1404 amino acids in size with multiple functional domains similar to vitronectin. The reported structure of MSF contains a centrally located mucin (exon 6) with 76 repeats of the degenerate motif of KEPAPTT, the presumed site of extensive O-linked glycosylation. RT-PCR with primers complementary for Pro214- Ala307 in exon 6 and RNA from human synovial fibroblasts produced the predicted product size of 280 bp.",
            "output": [
                "Is lubricin a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts?"
            ]
        },
        {
            "id": "task847-bb547710f1e9415f99479f2ef9d6b023",
            "input": "To determine the clinical significance of IgG antibodies to type II collagen (CII) and to define any correlation of antibodies to CII with the inflammatory response in patients with rheumatoid arthritis (RA).', 'IgG antibodies to native human type II collagen (IgG anti-CII) were measured in sera and synovial fluid (SF) from patients with RA, patients with osteoarthritis (OA), and healthy controls by an improved ELISA. Demographic, clinical, and laboratory data including tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) levels were also obtained at the time of sampling in patients with RA.', 'The median level and positivity for circulating IgG anti-CII were higher in patients with RA (n = 297) than patients with OA (n = 34) and healthy controls (n = 50) (p < 0.001). The titers of IgG anti-CII in SF were also higher in RA (n = 45) than in OA (n = 16) (p < 0.001). In paired samples, the levels of IgG anti-CII were significantly higher in SF compared to the sera in patients with RA (n = 45) (p < 0.001), but levels were not different in patients with OA (n = 16). Circulating IgG anti-CII converted from positive to negative in 13 patients (10.7%) and from negative to positive in 18 patients (14.8%) among 122 patients with RA in whom IgG anti-CII were monitored sequentially at a mean interval of 12.2 months. IgG anti-CII positive patients (n = 98) had shorter disease duration (p = 0.04) and less frequent deformity (p = 0.013), and higher median erythrocyte sedimentation rate (ESR) (p = 0.001) and C-reactive protein (CRP) (p < 0.001) than IgG anti-CII negative patients (n = 120). The levels of IgG anti-CII correlated with CRP (r = 0.270) and ESR (r = 0.253). CRP decreased significantly in patients (n = 13) who converted from IgG anti-CII positive to negative (p = 0.013). IgG anti-CII positive patients (n = 40) had higher levels of TNF-alpha and IL-6 than negative patients (n = 40) (p < 0.001). Levels of IgG anti-CII correlated well with TNF-alpha (r = 0.617) and IL-6 (r = 0.347).",
            "output": [
                "Do igG antibodies to type II collagen reflect inflammatory activity in patients with rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-aff0f0a912d14c0fa6a07664b74c8545",
            "input": "Atherosclerosis is a multigenic process leading to the progressive occlusion of arteries of mid to large caliber. A key step of the atherogenic process is the proliferation and migration of vascular smooth muscle cells into the intimal layer of the arterial conduit. The phenotype of smooth muscle cells, once within the intima, is known to switch from contractile to de-differentiated, yet the regulation of this switch at the genomic level is unknown. Estrogen has been shown to regulate cell proliferation both for cancer cells and for vascular cells. However, methylation of the estrogen receptor-alpha gene (ERalpha) promoter blocks the expression of ERalpha, and thereby can antagonize the regulatory effect of estrogen on cell proliferation. We sought to determine whether methylation of the ERalpha is differentially and selectively regulated in contractile versus de-differentiated arterial smooth muscle cells.', 'We used Southern blot assay, combined bisulfite restriction analysis (Cobra) and restriction landmark genome scanning (RLGS-M) to determine the methylation status of ERalpha in human aortic smooth muscle cells, either in situ (normal aortic tissue, contractile phenotype), or the same cells explanted from the aorta and cultured in vitro (de-differentiated phenotype).', 'We provide evidence that methylation of the ERalpha in smooth muscle cells that display a proliferative phenotype is altered relative to the same cells studied within the media of non-atherosclerotic aortas. Thus, the ERalpha promoter does not appear to be methylated in situ (normal aorta), but becomes methylated in proliferating aortic smooth muscle cells. Using a screening technique, RLGS-M, we show that alteration in methylation associated with the smooth muscle cell phenotypic switch does not seem to require heightened activity of the methyltransferase enzyme, and appears to be selective for the ERalpha and a limited pool of genes whose CpG island becomes either demethylated or de novo methylated.",
            "output": [
                "Is methylation of the estrogen receptor-alpha gene promoter selectively increased in proliferating human aortic smooth muscle cells?"
            ]
        },
        {
            "id": "task847-230d22859e01432db809fb7ac3e242bd",
            "input": "Sphingosine 1-phosphate is a naturally occurring biologically active lysophospholipid. Recent studies suggested that sphingosine 1-phosphate is released into the blood flow from activated platelets upon stimulation to exert multiple biological phenomenon. The purpose of this study was to assess the effects of sphingosine 1-phosphate on sinus automaticity, ventricular contraction and coronary blood flow.', 'The canine isolated, blood-perfused sinoatrial node and papillary muscle preparations were used.', 'Sphingosine 1-phosphate increased the sinoatrial rate, while it decreased the coronary blood flow, which was followed by a weak negative inotropic effect. These positive chronotropic and coronary vasoconstrictor effects were not attenuated by the beta- and alpha-adrenoceptor antagonists atenolol and prazosin, respectively. Furthermore, sphingosine 1-phosphate did not affect the adenylate cyclase activity of the membrane preparations made from the canine right atrium and right ventricle, indicating the involvement of a novel signaling pathway in sphingosine 1-phosphate-induced cardiac effects.",
            "output": [
                "Does sphingosine 1-phosphate induce sinus tachycardia and coronary vasoconstriction in the canine heart?"
            ]
        },
        {
            "id": "task847-5317701683e047c38317a84408eb64b0",
            "input": "This study was performed to assess whether there is any change in the T cell cytokine pattern in early rheumatoid arthritis (RA) patients treated with methotrexate (MTX) and whether the lymphocytic cytokine pattern correlates with disease activity.', 'Eight patients with RA (disease duration < six months) were studied serially before, after three, and after six to nine months of treatment with MTX for the cytokines tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin 4 (IL4) and interleukin 10 (IL10) by intracellular staining of T cells derived from peripheral blood. Response to treatment was assessed by the modified disease activitiy score.', 'The clincial response was accompanied by a significant decrease of TNFalpha positive CD4(+) T cells from a median of 8.53% (interquartile range 5.83-10.91%) before treatment to 6.17% (2.15-6.81%) after six to nine months of treatment (p=0.021). Inversely, IL10 positive T cells increased from a median of 0.65% (interquartile range 0.6-0.93%) to a median of 1. 3% (1.22%-1.58%) after six to nine months of treatment (p=0.009). No significant change in the percentage of INFgamma positive T cells and a small decrease of IL4 positive T cells during treatment were observed. The percentage of IL4 positive CD4(+) T cells before treatment correlated with disease activity after six to nine months (r= -0.7066; p=0.05).",
            "output": [
                "Is response to methotrexate in early rheumatoid arthritis associated with a decrease of T cell derived tumour necrosis factor alpha , increase of interleukin 10 , and predicted by the initial concentration of interleukin 4?"
            ]
        },
        {
            "id": "task847-0423dbb7018747038869338b82c1e5df",
            "input": "No previous studies have investigated the psychiatric characteristics of patients with postherpetic neuralgia (PHN). Similarly, no studies have been performed on patients with different chronic somatic symptoms due to a defined medical disease to compare the characteristics of psychiatric morbidity associated with each etiology.', 'After completing the subscales of the Symptom Checklist 90-R, a psychiatrist administered the Diagnostic Interview Schedule to all subjects. The psychiatric comorbidity in 35 patients with pain due to PHN was compared with a control group of 34 patients with the nonpainful aversive symptom of vertigo due to a peripheral vestibular disorder that caused unilateral hypofunction.', 'PHN patients had significantly more symptoms of major depression and somatization disorder. No significant differences were found between groups for psychiatric diagnoses. Patients with PHN reported significantly less acutely distressing somatic symptoms.",
            "output": [
                "Do psychiatric symptoms and distress differ between patients with postherpetic neuralgia and peripheral vestibular disease?"
            ]
        },
        {
            "id": "task847-7659495f11f14d5499b51163bc43a7d6",
            "input": "This study examines how alexithymia and depression are related to each other in men and women in a sample of Finnish general population (n = 2018).', 'Alexithymia was screened using the 20-item version of the Toronto Alexithymia Scale. Level of depression was assessed using the 21-item Beck Depression Inventory (BDI). Life satisfaction was estimated with a structured scale.', 'The prevalence of alexithymia was 12.8% in men and 8.2% in women. However, the prevalence of alexithymia was 32.1% among those having BDI scores of > or = 9, but only 4.3% among the nondepressed subjects (p < 0.001). The BDI scores explained 29.2% of the variation in TAS-20 scores. Alexithymia was associated with several sociodemographic factors if depression was not taken into account. However, after including depression in the logistic regression models, only depression and low life satisfaction were associated with alexithymia, both in men and women.",
            "output": [
                "Is depression strongly associated with alexithymia in the general population?"
            ]
        },
        {
            "id": "task847-c856d3eafc184be7861622cbef13190f",
            "input": "To determine whether endothelin (ET)-dependent effects limit shear stress-induced dilation of large epicardial coronary arteries after blockade of nitric oxide (NO) formation.', 'In conscious dogs instrumented for measuring coronary blood flow (CBF) and external diameter (CD) of the circumflex coronary artery, flow-dependent CD dilation was elicited by intracoronary (i.c.) adenosine (500 ng kg-1 min-1).', 'I.c. adenosine increased CBF by 28 +/- 4 from 38 +/- 5 ml min-1 and CD by 0.25 +/- 0.03 from 3.53 +/- 0.07 mm without other hemodynamic effects. After N omega-nitro-L-arginine methyl ester (L-NAME), baseline CD fell (P < 0.01) to 3.35 +/- 0.08 mm but CBF was not significantly altered (36 +/- 5 ml min-1). CBF increases caused by adenosine were smaller (17 +/- 2 ml min-1, P < 0.05) and CD responses were nearly abolished (0.02 +/- 0.01 mm, P < 0.01). I.c. Ro 61-1790, an ETA receptor blocker, given after L-NAME did not significantly influence baseline CBF (36 +/- 5 ml min-1) but increased (P < 0.01) CD to 3.45 +/- 0.09 mm. CBF responses to adenosine were not significantly altered by Ro 61-1790 but CD responses (0.10 +/- 0.01 mm) were partially restored (P < 0.01). In contrast, blockade of ETB receptors with Ro 46-8443 after L-NAME had no further effects on CD and CBF responses to adenosine.",
            "output": [
                "Do endothelin-dependent effects limit flow-induced dilation of conductance coronary vessels after blockade of nitric oxide formation in conscious dogs?"
            ]
        },
        {
            "id": "task847-0e67d22f840d458c80ca0700b27b899c",
            "input": "Ovarian cancer is a well-known disease with a poor prognosis. Due to the relatively small number of cases in Taiwan, the outcome and prognostic factors of patients with primary epithelial ovarian carcinoma are unknown.', \"We retrospectively studied patients with proven surgical and pathologic (Federation Internationale de Gynecologie et d'Obstetrique) FIGO IIIC primary epithelial ovarian carcinoma. All patients underwent standard staging surgery, including washing cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, retroperitoneal lymphadenectomy, infracolic omentectomy and excisional biopsy of all suspicious lesions followed by adjuvant chemotherapy with four to 12 courses of cyclophosphamide, epirubicin and cisplatin (CEP) or cyclophosphamide, adriamycin and cisplatin (CAP) intravenously, every three weeks. To avoid the coeffects of chemotherapy and surgical procedures upon the outcome, patients who received paclitaxel-based regimens or underwent incomplete surgery were excluded. Ninety-eight patients from 1990 to 1996 were identified.\", 'The mean follow-up time was 28.7 months, ranging from 5.4 months to 105.9 months. The cumulative five-year disease-free survival rate for all patients was 31.6%. Optimal debulking surgery was completed in 41.8% of patients, which contributed to long-term patient survival (54% vs 16%, p < 0.0001), compared to patients without optimal debulking surgery. Optimal debulking surgery was the only statistically significant independent prognostic factor for five-year disease-free survival using multivariate analysis.",
            "output": [
                "Is optimal debulking surgery an independent prognostic factor in patients with FIGO IIIC primary epithelial ovarian carcinoma?"
            ]
        },
        {
            "id": "task847-0dc01a895b164f12b07c481d532c1ef5",
            "input": "Hepatic resection is well established as a potentially curative treatment for hepatic colorectal cancer metastases. However, only a small proportion of patients with liver metastases are suitable for resection because they either have extrahepatic disease, or the extent and/or the distribution of their hepatic disease would make excision impossible. We have previously described the use of cryotherapy for inadequate resection margins and lesions in the remaining lobe of the liver. Combining such cryodestructive techniques with resection offers the possibility of increasing the proportion of patients to whom potentially curative treatment can be offered. The aim of this study was to compare survival in patients treated with resection and cryotherapy against those of patients treated with resection alone. Potential prognostic variables were also examined.', 'Patients undergoing a hepatic resection with or without cryotherapy at our unit between April 1990 and July 1997 were identified from our database and their notes reviewed. Survival was estimated using the Kaplan-Meier method and compared using the Log rank test.', 'One hundred and seven patients were treated in total: 32 underwent resection alone, and 75 underwent resection combined with cryotherapy. There was no significant difference between the survival of patients treated with resection alone and those treated with resection and cryotherapy.",
            "output": [
                "Does resection with cryotherapy of colorectal hepatic metastases have the same survival as hepatic resection alone?"
            ]
        },
        {
            "id": "task847-a6340ac4afa54de791b584504425648f",
            "input": "We have performed TNF-alpha gene transfection in a mouse mammary cancer line and found significant antitumor effects. We hypothesize that the antitumor effects observed in this model are mediated by ICAM-1 and by the recruitment of CD4+ and CD8+ T cells. In vivo (Balb/c mice) tumor growth inhibition, treatment of established tumor and the effects of ICAM-1 and CD4+ and CD8+ T cells were evaluated.', 'Gene transfection with highly efficient vectors resulted in secretion of large amounts of TNF-alpha (ELISA). In vivo antitumor effects were tested. The number of cells required to generate palpable tumor 7-10 days after subcutaneous injection was determined (1 x 10(6)). The same number of transfected cells were injected subcutaneously and compared to nontransfected controls. Tumors were measured blindly and size was analyzed on day 30 by the Wilcoxon rank sum test. Mean tumor size after injection of transfected cells is compared to that of controls. Control tumors reached the maximum allowable size by day 30 (4 cm(2)). On day 30 EMT6-TNF-alpha tumors were 0.48 cm(2) (p < 0.05). The effect of repeat injection (challenge was also tested. Animals were injected with transfected cells or wild-type control on day -6 and challenged with the same number of wild-type tumor cells on day 0. Significant immune protection against subsequent challenge was seen after first time injection with EMT6-TNF-alpha but not after first time EMT6 wild-type injection (1.62 vs. 4 cm(2)). Treatment of 6-day-old tumor was also evaluated. On day 30, mean tumor size in animals treated with EMT6-TNF-alpha was 0.9 cm(2) compared to 4 cm(2) for controls. In all experiments, CD8+ T cell depletion and CD4+ T cell depletion caused a reversal of TNF-alpha-induced inhibitory effects. In addition, in vivo antibody blocking of ICAM-1 in tumor growth experiments reversed antitumor effects (control 4 cm(2), TNF-alpha 0.2 cm(2) and ICAM-1 blocking 3.14 cm(2)). Using flow cytometry, MHC class I and II and ICAM-1 adhesion molecule expression of transfected tumor was tested. ICAM-I expression was significantly upregulated. MHC class II antigen expression was also increased. TNF-alpha-transfected human breast cancer was also evaluated. Three cell lines and fresh tumor were transfected to express TNF-alpha. In vitro analysis revealed ICAM-1 upregulation following transfection. Histologic analysis and immunohistochemical staining revealed TNF-alpha and ICAM-1 in transfected tumors and not in wild-type tumors.",
            "output": [
                "Is treatment of established tumor associated with ICAM-1 upregulation and reversed by CD8 depletion in a tumor necrosis factor-alpha gene transfected mouse mammary tumor?"
            ]
        },
        {
            "id": "task847-fd7c99fb898d48e892c9959d2a31df9c",
            "input": "To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion.', 'Prospective, randomized, controlled experimental study.', 'University-affiliated animal research laboratory.', 'Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes.', 'Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10).', 'Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group.",
            "output": [
                "Does specific angiotensin II receptor blockage improve intestinal perfusion during graded hypovolemia in pigs?"
            ]
        },
        {
            "id": "task847-6aeb8c09764f4792b19c37c689f083f4",
            "input": "To investigate the effect of multiple-dose paroxetine intake on the stereoselective pharmacokinetics and the pharmacodynamics of metoprolol.', 'We conducted an open trial with two sessions in eight healthy male volunteers. Racemic metoprolol (100 mg single oral dose) was administered before and after paroxetine treatment (20 mg/day for 6 days). The (R)- and (S)-metoprolol pharmacokinetics, metoprolol metabolic ratio (MR), exercise heart rate and blood pressure were assessed for 12 (pharmacodynamic data) to 24 (pharmacokinetic data) hours after each metoprolol intake.', 'Paroxetine treatment increased the mean area under the plasma concentration-time curve extrapolated to infinity (AUC) of (R)- and (S)-metoprolol significantly (169 to 1,340 ng x h/mL [P < .001] and 279 to 1,418 ng x h/mL [P < .001], respectively), with an approximately twofold increase in both maximum plasma concentration and terminal elimination half-life. Furthermore, the (S)/(R) AUC ratio was significantly decreased, from 1.72 to 1.07 (P < .001). The mean metoprolol MR was significantly increased, from 0.17 to 5.69 (P < .05). The AUC of the metoprolol-induced decrease in exercise heart rate versus time curve was increased, with 46% (P < .01) after multiple-dose paroxetine intake, reaching significance from 6 hours after metoprolol intake, illustrating a more sustained beta-blockade. Similar results were obtained for the effect on exercise systolic blood pressure. Multiple-dose metoprolol administration combined with paroxetine can lead to an accumulation of the beta-blocking (S)-enantiomer of metoprolol, possibly resulting in unacceptable bradycardia, loss of cardioselectivity, or both.",
            "output": [
                "Does paroxetine affect metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers?"
            ]
        },
        {
            "id": "task847-929b931fcf6f422688144b808a3e4ecc",
            "input": "To evaluate if the preexistant filling state, assessed by right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), and right ventricular end-diastolic volume index (EDVI), would define the subsequent hemodynamic effects of increases in airway pressure (Paw).', 'Prospective open clinical study.', 'Postoperative intensive care unit, university hospital.', 'Twenty-two consecutive ventilator-dependent patients with mild to severe acute lung injury with Murray scores (scoring infiltrates on chest radiograph, oxygenation index, lung compliance, and the level of positive end-expiratory pressure) ranging from 0.5 to 3.0 without history of preexisting cardiopulmonary disease.', 'Paw varied during apnea from 0 to 10, 20, and 30 cm H2O using inspiratory hold maneuvers of 15 secs.', 'Cardiac index and right ventricular ejection fraction were measured by the thermodilution technique. We made measurements in triplicate using manual injection of iced saline. Right ventricular volumes were calculated. Increasing Paw induced variable changes in cardiac index among subjects (+6% to -43% change from baseline 0 cm H2O Paw values), which correlated with percentage changes in both stroke index (r2 = .89) and right ventricular EDVI (r2 = .75), whereas heart rate and right ventricular ejection fraction did not change. The change in cardiac index from 0 to 30 cm H2O Paw correlated with baseline values for RAP, PAOP, and right ventricular EDVI (r2 = .68, .43, and .34, respectively, p < 0.01). Increases in RAP correlated with lung compliance if baseline RAP was >10 mm Hg but did not if it was < or =10 mm Hg. Similarly, patients with baseline RAP < or =10 mm Hg had a greater decrease in cardiac index than patients with a RAP >10 mm Hg (for 30 cm H2O Paw: -30% +/- 9% vs. -8% +/- 7%, p < .01).",
            "output": [
                "Does right atrial pressure predict hemodynamic response to apneic positive airway pressure?"
            ]
        },
        {
            "id": "task847-c386f2f4eb9c44159328dbcc8678db62",
            "input": "To investigate the additional effect of incentive spirometry to chest physiotherapy to prevent postoperative pulmonary complications after thoracic surgery for lung and esophageal resections.', 'Randomized controlled trial.', 'University hospital, intensive care unit, and surgical department.', 'Sixty-seven patients (age, 59 +/- 13 yrs; forced expiratory volume in 1 sec, 93% +/- 22% predicted) undergoing elective thoracic surgery for lung (n = 40) or esophagus (n = 27) resection.', 'Physiotherapy (breathing exercises, huffing, and coughing) (PT) plus incentive spirometry (IS) was compared with PT alone.', 'Lung function, body temperature, chest radiograph, white blood cell count, and number of hospital and intensive care unit days were all measured. Pulmonary function was significantly reduced after surgery (55% of the initial value) and improved significantly in the postoperative period in both groups. However, no differences were observed in the recovery of pulmonary function between the groups. The overall score of the chest radiograph, based on the presence of atelectasis, was similar in both treatment groups. Eight patients (12%) (three patients with lobectomy and five with esophagus resection) developed a pulmonary complication (abnormal chest radiograph, elevated body temperature and white blood cell count), four in each treatment group. Adding IS to regular PT did not reduce hospital or intensive care unit stay.",
            "output": [
                "Does incentive spirometry enhance recovery after thoracic surgery?"
            ]
        },
        {
            "id": "task847-a80d4eb0c041406595677552f7debd3a",
            "input": "Primary effusion lymphoma (PEL) associates with HHV-8 infection, preferentially develops in immunodeficient patients and grows in the serous body cavities. PEL derives from post-germinal center, pre-terminally differentiated B-cells. The pathogenesis of PEL is unclear and the sole identified genetic lesions are human herpesvirus type-8 (HHV-8) infection in all cases and EBV infection in 70% of cases. Epstein-Barr virus (EBV) infection in PEL displays a latency I phenotype.', 'To clarify the pathogenesis and histogenesis of PEL by investigating (1) the lymphoma karyotype; (2) the expression status of the Met tyrosine kinase receptor and of its ligand hepatocyte growth factor (HGF); (3) the molecular profile of EBV, with particular focus on mutations of EBNA-1 genes, which are thought to affect viral tumorigenicity in EBV-infected neoplasms displaying the latency I phenotype.', 'Twenty-four PEL (nine cell lines and 15 primary specimens) formed the basis of the study. Karyotypes were investigated by conventional cytogenetics and fluorescent in situ hybridization (FISH) in selected cases. The expression status of Met and HGF was defined by multiple techniques, including RT-PCR, FACS analysis, immunocytochemistry, Western blot studies and ELISA. The molecular profile of EBNA-1 genes of EBV were investigated by DNA direct sequencing.', 'Trisomy 7, trisomy 12 and breaks at 1q21-q25 are recurrently associated with PEL. PEL consistently co-express Met and HGF both at the mRNA and protein level. Among aggressive B-cell lymphomas, Met/HGF co-expression appears to be relatively specific for PEL. The EBNA-1 gene of EBV displays a high degree of genetic heterogeneity in PEL, with no preferential association with one specific variant.",
            "output": [
                "Does molecular characterization of HHV-8 positive primary effusion lymphoma reveal pathogenetic and histogenetic features of the disease?"
            ]
        },
        {
            "id": "task847-3e78c1e79344486ea6753ab7351b5784",
            "input": "Methylenedioxymethamphetamine (MDMA) is known to damage brain pre-synaptic serotonin (5-HT) neurons. Since loss of 5-HT neurons has been implicated in memory loss, it is important to establish whether MDMA use may produce changes in postsynaptic 5-HT receptors and memory function in humans.', 'To investigate whether MDMA use leads to compensative alterations in post-synaptic 5-HT2A receptors and whether there is a relation with memory disturbances.', 'Brain cortical 5-HT2A receptor densities were studied with [123I]-5-I-R91150 SPECT in five abstinent MDMA users and nine healthy controls. Memory performance was assessed using RAVLT.', '[123I]-5-I-R91150 binding ratios were significantly higher in the occipital cortex of MDMA users than in controls, indicating up-regulation. Mean cortical 5-HT2A receptor binding correlated positively with RAVLT-recall in MDMA users.",
            "output": [
                "Are memory disturbances in `` Ecstasy '' users correlated with an altered brain serotonin neurotransmission?"
            ]
        },
        {
            "id": "task847-d38a3ed70ff0469080a0e90a1ad1bca7",
            "input": "Amphetamine (AMPH)-like stimulants represent an intensively studied class of psychoactive drugs. Despite the well-known and potent arousal-enhancing effects of these drugs, the neurobiological substrates of AMPH-induced arousal have rarely been examined explicitly. Activity of the locus coeruleus-noradrenergic system is causally and positively related to behavioral and electroencephalographic (EEG) indices of arousal. For example, activation of locus coeruleus neurons or stimulation of medial basal forebrain noradrenergic beta-receptors elicits activation of forebrain EEG in the anesthetized rat. Further, stimulation of noradrenergic beta-receptors within the medial basal forebrain elicits a substantial increase in alert, active waking. These and other observations suggest that at least some of the arousal-enhancing actions of AMPH-like stimulants derive from AMPH-induced increases in noradrenergic neurotransmission at beta-receptors. The current study examines the extent to which AMPH-induced activation of cortical EEG is dependent on actions of central beta-receptors.', 'The effects of intracerebroventricular (ICV; 2 microl) pretreatment with either vehicle (artificial extracellular fluid) or the beta-antagonist, timolol (25, 50 or 100 microg), on the cortical EEG activating effects of intravenous AMPH (0.15 mg/kg) were examined in the halothane-anesthetized rat. EEG was recorded on polygraph and video recording tape and later analyzed using power spectral analyses (PSA). AMPH-induced alteration in cortical EEG activity was measured using PSA in vehicle- and timolol-pretreated animals.', 'Neither vehicle nor timolol ICV infusions altered cortical EEG activity patterns. In vehicle-pretreated animals, AMPH elicited a robust activation of cortical EEG, characterized by the substantial decrease in large-amplitude, slow-wave activity. Timolol pretreatment dose-dependently prevented AMPH-induced cortical EEG activation. This effect of timolol was statistically significant at the 50 microg and 100 microg dose.",
            "output": [
                "Is amphetamine-induced activation of forebrain EEG prevented by noradrenergic beta-receptor blockade in the halothane-anesthetized rat?"
            ]
        },
        {
            "id": "task847-ecbbd6efb5c24e1082dd00be52ab8fa3",
            "input": "There is evidence from animal studies that lactose has a beneficial effect on intestinal calcium absorption. However, data concerning the effect of lactose on calcium absorption in lactose-tolerant adults are inconclusive.', 'Our objective was to investigate the effect of lactose on calcium bioavailability in humans by the use of a stable-strontium test under controlled metabolic conditions.', 'Eleven healthy, lactose-tolerant subjects (8 women, 3 men) randomly received a bolus of 2.27 mmol strontium alone (load A), the bolus with 35 g lactose (load B), or the bolus with 17.5 g glucose and 17.5 g galactose (load C). Blood samples were drawn at 0, 15, 30, 60, 90, 180, 240, and 300 min. Urine specimens were collected during the time intervals -2 to 0, 0-2, 2-4, 4-6, and 6-24 h.', 'Pharmacokinetic parameters of strontium bioavailability were comparable for all 3 loads. In detail, fractional absorption at 240 min for loads A, B, and C was 12.1 +/- 0.7%, 13.0 +/- 1.1%, and 12.2 +/- 0.7%, respectively. Areas under the curve for 0-240 min were 70.8 +/- 6.3, 69.6 +/- 3.5, and 65.8 +/- 5.1 micromol*h/L for loads A, B, and C, respectively (NS). Moreover, fractional strontium excretion values of 5.1 +/- 0.8% (load A), 5.8 +/- 0.4% (load B), and 5.2 +/- 0.8% (load C) were not significantly different.",
            "output": [
                "Does lactose enhance calcium bioavailability in lactose-tolerant , healthy adults?"
            ]
        },
        {
            "id": "task847-d91cc34c005545dda55b1ac7a5e24fb2",
            "input": "n-3 Fatty acids lower plasma triacylglycerols not only in the fasting state but also in the postprandial state. However, it is not known whether chylomicrons, chylomicron remnants, and VLDLs are all affected equally or whether some lipoprotein species are lowered preferentially.', 'Lipoproteins, including large and small chylomicron remnants, were determined specifically with the aid of a newly developed method involving a combination of size-exclusion chromatography and fluorometric determination of retinyl palmitate, which served as a marker for exogenous fat.', 'Twelve hypertriacylglycerolemic men were treated for 6 wk with 4 capsules containing 85% fish-oil concentrate/d; each capsule contained 850 mg n-3 fatty acid ethyl esters (49.1% eicosapentaenoic acid by wt and 32.2% docosahexaenoic acid by wt). Oral-fat-tolerance tests were performed before and after the treatment. Blood samples were drawn in the fasting state and until 8 h postprandially.', 'Treatment with n-3 fatty acids reduced the fasting VLDL-triacylglycerol concentration by 44% (P < 0.05) and postprandial chylomicrons and VLDLs at 4, 6, and 8 h (P < 0.05) by 49-64% and 36-43%, respectively. Chylomicron remnants were reduced only in the late postprandial phase: large chylomicron remnants by 19% at 6 h and by 43% at 8 h (P < 0.05) and small chylomicron remnants by 31% at 8 h (P < 0.05).",
            "output": [
                "Are postprandial chylomicrons and VLDLs in severe hypertriacylglycerolemia lowered more effectively than are chylomicron remnants after treatment with n-3 fatty acids?"
            ]
        },
        {
            "id": "task847-9a1e558b269340488acf32d1ca2ce3f1",
            "input": "Adipose tissue (AT) content of the thigh is generally not considered to be associated with insulin resistance (IR), but it is unclear whether the distribution of AT in the thigh is a determinant of IR.', 'We investigated whether subcompartments of AT within the thigh are determinants of IR.', 'Midthigh AT, muscle composition, and insulin sensitivity were compared in 11 obese patients with type 2 diabetes mellitus (DM); 40 obese, glucose-tolerant (GT) and 15 lean, GT volunteers; and 38 obese subjects who completed a weight-loss program. Midthigh AT area measured with computed tomography was partitioned into 3 components: subcutaneous AT (SCAT), AT beneath the fascia (SFAT), and AT infiltrating muscle groups (IMAT). Muscle attenuation characteristics were determined.', 'Obese DM and obese GT subjects had lower insulin sensitivity than lean GT subjects. SCAT was greater in obesity, yet did not correlate with insulin sensitivity. SFAT was approximately 8% of total thigh AT and correlated with insulin sensitivity. IMAT was highest in obese DM, and although it accounted for only approximately 3% of thigh AT, it was a strong correlate of insulin sensitivity. Mean attenuation was highest in lean subjects and was associated with higher insulin sensitivity. Weight loss reduced the amount of thigh AT, the proportion of thigh IMAT, and the amount of low-density thigh muscle.",
            "output": [
                "Is thigh adipose tissue distribution associated with insulin resistance in obesity and in type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-271e85956d6b4a38a0db9e3f9c331d7b",
            "input": "The influence of age on early and late outcome after surgical resection of bronchogenic carcinoma is unknown. In an attempt to clarify this issue, we reviewed the outcome of 212 consecutive patients with primary lung cancer who had surgical treatment for bronchogenic carcinoma.', 'Ninety-two patients were younger than 50 years (group 1), and 120 patients were older than 70 years of age (group 2). Squamous cell carcinoma and adenocarcinoma were the most common histologic types in both groups. According to the new international staging classification, a similar proportion of stage I, II, and III were observed in both groups.', 'Only the rate of pneumonectomy was significantly higher in younger patients (41% versus 22%, p = 0.002). The overall operative mortality rate in group 1 was 2.2% and 2.6% after pneumonectomy. In group 2 the overall mortality rate was 2.5% and 3.8% after pneumonectomy. Advanced age did not affect operative mortality. The adjusted (tumor-related) survival rate at 5 years was 56% in group 1 and 53% in group 2 (p = 0.93). The adjusted survival rate for patients with stage I was 61% in group 1 and 65% in group 2 (p = 0.21), and for stage IIIa 39% in group 1 and 48% in group 2 (p = 0.43). The adjusted 5-year survival rate was 56% in group 1 and 59% in group 2 for squamous cell carcinoma (p = 0.53) and 49% in group 1 and 42% in group 2 for adenocarcinoma (p = 0.76).",
            "output": [
                "Does age influence early and late tumor-related outcome for bronchogenic carcinoma?"
            ]
        },
        {
            "id": "task847-3796cddb01364ddbbde07100b214a836",
            "input": "The heat shock protein (hsp27) correlates with thermotolerance and chemoresistance. Our main objective was to assess the response to radiotherapy both in vitro and in vivo in correlation with various concentrations of hsp27. The second objective was to evaluate the relation between hsp27 and glutathione-s-transferase pi (GST pi).', 'For the in vitro study, thermoresistant cell lines, expressing various amounts of hsp27, were used to assess the role of this protein in radioresistance. To verify the efficiency of hsp27 in these cells lines to confer resistance to cytotoxic agents, these cells were also treated with heat shock and cisplatin. Furthermore, the role of hsp27 expression was studied in vivo by immunochemistry in 98 patients with head and neck squamous cell carcinoma treated by radiotherapy. hsp27 was correlated with local control of the tumor and with clinical and biologic factors potentially able to affect the local control, including p53, ki-67, ploidy, and GST.', 'In vitro, high constitutive levels of expression of hsp27 did not significantly influence the survival curves of transfected cells exposed to radiation as compared to control cells although hsp27 overexpression was confirmed to increased the cellular resistance to heat and to cisplatinum. In vivo, we showed that overexpression of various amounts of hsp27 did not correlate with local control of the tumor. In vivo, hsp27 was only significantly associated with GST pi. Expression of GST pi was associated with poor local (p = 0.01) control and survival (p = 0.08) in a Cox model.",
            "output": [
                "Is overexpression of the 27 KDa heat shock protein associated with thermoresistance and chemoresistance but not with radioresistance?"
            ]
        },
        {
            "id": "task847-34bdf91f7ebb4512b654cb44178461db",
            "input": "We tested the hypothesis that propofol, acting in the brain, would either enhance, or have no effect, on lumbar dorsal horn neuronal responses to a noxious mechanical stimulus applied to the hindlimb. We recorded the response of lumbar dorsal horn neurons during differential delivery of propofol to the brain and torso of goats.', 'Goats were anesthetized with isoflurane and neck dissections performed which permitted cranial bypass. A laminectomy was made to allow microelectrode recording of lumbar dorsal horn neuronal activity. Isoflurane was maintained at 0.8+/-0.1% to both head and torso throughout the study. During cranial bypass propofol was separately administered to the torso (1 mg x kg(-1), n = 7; 3.75 mg x kg(-1), n = 8) or cranial (0.04 mg x kg(-1), n = 7; 0.14 mg kg(-1), n = 8) circulations.', 'Propofol administered to the torso depressed dorsal horn neuronal responses to noxious stimulation: low dose: 500+/-243 to 174+/-240 impulses x min(-1) at one minute post-injection, P<0.001; high dose: 478+/-204 to 91+/-138 impulses x min(-1) at one minute post-injection, P<0.05). Propofol administered to the cranial circulation had no effect: low dose: 315+/-150 to 410+/-272 impulses x min(-1), P>0.05; high dose: 462+/-261 to 371+/-196 impulses x min(-1), P>0.05.",
            "output": [
                "Does propofol directly depress lumbar dorsal horn neuronal responses to noxious stimulation in goats?"
            ]
        },
        {
            "id": "task847-f48413d5541f436095e56a1b86499c6e",
            "input": "Retinal pigment epithelial (RPE) cells are believed to play a pivotal role in the formation and contraction of epiretinal membranes in proliferative vitreoretinopathy (PVR). In the present study, an organ culture method was used that mimics the contractile stage of PVR, to investigate the contribution of a variety of growth factors in human RPE cell-mediated contraction of the retina.', 'Cultured human RPE cells were seeded onto bovine retinal explants. After attachment, cultures received one of the following exogenous growth factors: platelet-derived growth factor (PDGF)-AB, PDGF-BB, basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-beta1, TGF-beta2, or interleukin (IL)-10; or a neutralizing antibody to PDGF and/or TGF-beta2. Control explants were either untreated or received a null antibody. Contraction was assessed by image analysis and expressed as percentage reduction in retinal area.', 'RPE cells produced a more than 50% contraction of the retina after 7 days in untreated samples. PDGF and TGF-beta2 stimulated RPE-mediated contraction by a further 20% at 100 ng/ml. IL-10 decreased contraction by 63%, whereas the other growth factors gave rise to similar contraction to untreated controls. Neutralizing antibodies against PDGF and TGF-beta2 reduced RPE-mediated contraction by up to 70% in comparison with untreated controls. The neutralizing antibodies also inhibited the effects of exogenous PDGF and TGF-beta2 on RPE-mediated contraction of the retina (P < 0.01).",
            "output": [
                "Do iL-10 and antibodies to TGF-beta2 and PDGF inhibit RPE-mediated retinal contraction?"
            ]
        },
        {
            "id": "task847-0e28cc0565374120a17bec14a87b60d4",
            "input": "Oesophageal cancer is generally associated with late presentation and poor prognosis. Therefore palliative surgery has been largely superseded by less invasive non-surgical techniques. Once palliation is indicated, the aims of the management should be: the maintenance of oral intake, minimizing hospital stay, relief of pain, elimination of reflux and regurgitation and the prevention of aspiration.', 'This study was a review of all published English language data on the palliation of malignant dysphagia between 1994-1999. The Medline and Bids databases were searched and other references were derived from the material perused.",
            "output": [
                "Do an update in the palliative management of malignant dysphagia?"
            ]
        },
        {
            "id": "task847-5a610ab176334783985d6c95bfe5ec72",
            "input": "We used a murine model of orthotopic corneal transplantation to determine whether host deficiency in ICAM-1 promotes survival of corneal grafts with different degrees of allodisparity.', 'ICAM-1-/- and wild-type C57BL/6 (ICAM-1+/+) received corneal grafts from the following strains of mice: BALB/c (fully mismatched), BALB.b (mismatched at multiple minor H only), or B10.D2 [including major histocompatibility complex (MHC) mismatch]. Graft rejection, induction of allospecific delayed-type hypersensitivity (DTH) responses, and leukocytic infiltration of grafts were measured.', 'There were no differences in long-term survival of allografts that were either fully mismatched or had only minor H disparity in ICAM-1+/+ vs. ICAM-1-/-hosts. However, whereas B10.D2 grafts were accepted in only 58% of the ICAM-1+/+ hosts, graft survival in ICAM-1-/- recipients was 100% (P=0.006). Moreover, none of the ICAM-1-/- mice receiving B10.D2 grafts developed allospecific DTH.",
            "output": [
                "Does iCAM-1 deficiency suppress host allosensitization and rejection of MHC-disparate corneal transplants?"
            ]
        },
        {
            "id": "task847-da2cadbe7cf94d228d3d42a4220714c4",
            "input": "Erythromycin has been found to be a gastrointestinal prokinetic agent of hypertonic liquids, while acute hyperglycemia has been associated with delayed gastric emptying in diabetic patients.', 'To investigate whether hyperglycemia, per se, reduces gastric motility during erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients.', 'In 12 type-I diabetic patients following a hypertonic radiolabeled liquid meal, gastric emptying was measured scintigraphically during normoglycemia (5-8.9 mmol/l glucose) or hyperglycemia induced by intravenous (16-19 mmol/l) glucose infusion. The tests were performed on 4 separate days in random order after administering either placebo or 200 mg i.v. erythromycin.', 'In the hyperglycemic state compared to normoglycemia, the gastric emptying of the hypertonic liquid was reduced after placebo or erythromycin administration. The lag-phase duration (17.8+/-5.5 and 7.8+/-4.5 vs. 10.8+/-3.4 and 3.7+/-2.5 min, respectively, p<0.001), the overall gastric emptying time of the half meal (52.8+/-13 and 24.9+/-5.5 vs. 42.5+/-10.5 min and 16.6+/-6 min, respectively, p<0.001) and the retained percentage of liquid meal in the stomach at 60 and 100 min postprandially (p<0.001) were significantly increased.",
            "output": [
                "Does induced-hyperglycemia attenuate erythromycin-induced acceleration of hypertonic liquid-phase gastric emptying in type-I diabetic patients?"
            ]
        },
        {
            "id": "task847-87b247cbf9b342c58449c49b1b0fd9e0",
            "input": "Age-related defects in the development of peripheral inflammatory responses have been observed in rodents and humans.', 'We examined the effects of age on a centrally injected endotoxin-induced cytokine production and cellular activation in mice.', 'Male C57BL/6J (B6) mice, C3H/HeN mice, and C3H/HeJ mice received an intracerebroventricular injection of lipopolysaccharide (LPS) and were sacrificed at various times (2, 4, 8 h) thereafter. ELISA for IL-1beta, IL-6, IL-12, and TNF-alpha were conducted on forebrain tissue homogenates as well as plasma samples, and lectin staining to detect activated microglia was prepared for selected brain slices.', 'Intracerebroventricular injection of LPS in B6 mice produced an age-associated increase in mortality which was paralleled with a significant increase in brain and plasma levels of TNF-alpha. AntiTNF-alpha- and IL-6-immunoreactive cells possessed macrophagelike morphologies and were observed along the LPS injection tract and scattered throughout the hilus of the dorsal hippocampus and cerebral cortices. This LPS-mediated response was found to be specific in that the LPS-hyporesponsive mouse strain (C3H/HeJ) failed to demonstrate significant brain or plasma levels of TNF-alpha after LPS administration compared to C3H/HeN mice.",
            "output": [
                "Do aged mice exhibit greater mortality concomitant to increased brain and plasma TNF-alpha levels following intracerebroventricular injection of lipopolysaccharide?"
            ]
        },
        {
            "id": "task847-d731656fff1148eb8c924b432efc8cbe",
            "input": "Radiofrequency applications to the posteroseptal region can ablate the atrioventricular accessory pathway residing in this area. In conjunction with the adjacent anatomic structures, however, ablative lesions which do not effectively ablate the accessory pathway could markedly alter retrograde atrial activation sequence and confound interpretation of further mapping of an accessory pathway.', 'Electrophysiologic studies, endocardial activation mapping and radiofrequency catheter ablation were undertaken in three patients with recurrent supraventricular tachycardia. Patients were initially thought to have a single posteroseptal accessory pathway; earliest ventrioatrial activation during tachycardias and during ventricular pacing was at the coronary sinus ostium, but initial radiofrequency applications were unsuccessful to ablate the pathway. After initial radiofrequency applications to the posteroseptal region, the earliest retrograde atrial activation changed to the right atrial free wall in two patients. Additional radiofrequency application to the posteroseptal area was able to ablate the single posteroseptal accessory pathway in one patient. Radiofrequency application to the right atrial free wall was required to stop tachycardia initiation in other patient. The third patient was suspected of having a slow-slow atrioventricular nodal reentry tachycardia. Radiofrequency application to the posteroseptal area changed the earliest retrograde atrial activation to the distal coronary sinus recording site, mimicking an accessory pathway at the left atrial free wall. Radiofrequency application to the anteroseptum was able to ablate the concealed accessory pathway.",
            "output": [
                "Does radiofrequency application to the posteroseptal region alter retrograde accessory pathway activation?"
            ]
        },
        {
            "id": "task847-b05fb6b89baf4a4493d889e3bf0e2eaf",
            "input": "This study investigated whether off-pump coronary bypass graft operations on the beating heart under normothermic conditions reduces the systemic oxidative stress and inflammatory reaction seen in patients operated under cardiopulmonary bypass (CPB).', 'A cardiac stabilizer (Octopus Tissue Stabilizer; Medtronic Inc, Minneapolis, MN) was used to perform the coronary anastomoses on the normothermic beating heart with or without CPB. Serial blood samples were taken at various intervals. Plasma was analyzed for several oxidative stress and inflammatory markers.', 'Significant increases from prior anesthesia values of lipid hydroperoxides (190% at 4 hours), protein carbonyls (250% at 0.5 hours) and nitrotyrosine (510% at 0.5 hours) were seen in the CPB group, but they were abolished or significantly reduced in the off-pump group. Complement C3a and elastase levels were rapidly increased upon the institution of CPB, and this was followed by increases in IL-8, TNF-alpha, and sE-selectin. In contrast, the rise of these factors was blunted in patients operated without CPB.",
            "output": [
                "Does off-pump bypass graft operation significantly reduce oxidative stress and inflammation?"
            ]
        },
        {
            "id": "task847-d799fe3db55c42dfb07aea537156d068",
            "input": "21-aminosteroids (lazaroids) have demonstrated the protective effect against cerebral ischemic injury through the inhibition of lipid peroxidation. We examined whether lazaroids affected the production of proinflammatory and antiinflammatory cytokines in ischemic spinal cord injury model.', 'Anesthetized New Zealand white rabbits underwent a 20-minute infrarenal aortic cross-clamping (AXC) with pretreatment of either an intravenous 3 mg/kg lazaroid U74389G (group L; n = 10) or the same volume saline (group P; n = 10). Sham operation group (group S; n = 6) underwent only exposure of the aorta. Plasma concentrations of interleukin (IL)-8, -1beta, -1 receptor antagonist (IL-1ra) and tumor necrosis factor (TNF)-alpha were measured at four time points. Functional assessment with Tarlov score at 24 and 48 hours after pretreatment, pathologic assessment of the spinal cord, and measurements of cytokine levels in the spinal cord were performed.', 'The maximum elevation of plasma IL-8 and -1ra levels occurred at 1 hour after declamping in four measurement points. Plasma IL-8 and -1ra levels in group L were significantly lower than those in group P (*p < 0.05). Plasma TNFalpha peaked at 5 minutes after declamping, but decreased afterwards. Plasma TNFalpha levels were not different among three groups. Spinal IL-8 levels in group L (0.98 +/- 0.34 ng/g tissue) were lower than those in group P (7.26 +/- 2.26 ng/g tissue)(*p < 0.05). Spinal IL-1ra and TNFalpha were not significantly different. Tarlov score and pathologic assessment were better in group L.",
            "output": [
                "Does lazaroid reduce production of IL-8 and IL-1 receptor antagonist in ischemic spinal cord injury?"
            ]
        },
        {
            "id": "task847-30a8c3f8fc29413abf646b528216c9f4",
            "input": "Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill patients with acute renal failure is still high. Previous efforts to predict the outcome in this population have been limited by small sample sizes. In addition, data obtained decades ago may not apply today owing to changes in the case mix. We have attempted to determine whether organ system failures can be used to predict prognosis.', 'The medical records of 100 consecutive intensive care unit patients with acute renal failure who required dialysis from January 1997 through December 1998 were evaluated by a blinded reviewer.', 'Of the 100 patients studied, 65 were men and 35 were women. The mean age of survivors and non-survivors was 59.4 +/- 20.3 years and 58.3 +/- 20.0 years, respectively. The overall mortality rate was 71%. There were no significant differences between survivors and non-survivors in age, gender, or indication for dialysis. The cause of death in the majority of patients was related to organ system failure, and they carried mortality rates exceeding 83% with the coexistence of four or more failed organs.",
            "output": [
                "Do organ system failures predict prognosis in critically ill patients with acute renal failure requiring dialysis?"
            ]
        },
        {
            "id": "task847-5805286336cb438d8e33cbedb0629e43",
            "input": "To assess the effect of newborn circumcision on the incidence and medical costs of urinary tract infection (UTI) during the first year of life for patients in a large health maintenance organization.', 'Kaiser Permanente Medical Care Program of Northern California (KPNC).', 'The population consisted of members of KPNC. The study group consisted of a cohort of 28 812 infants delivered during 1996 at KPNC hospitals; of the 14 893 male infants in the group, 9668 (64.9%) were circumcised. A second cohort of 20 587 infants born in 1997 and monitored for 12 months was analyzed to determine incidence rates.', 'Retrospective study of all infants consecutively delivered at 12 facilities.', 'Diagnosis of UTI was determined from the KPNC computerized database using the International Classification of Diseases, Ninth Revision code for inpatients and KPNC Outpatient Summary Clinical Record codes for outpatients. A sample of 52 patient charts was reviewed to confirm the International Classification of Diseases, Ninth Revision and KPNC Outpatient Summary Clinical Record codes and provide additional data.', 'Infants <1 year old who were born in 1996 had 446 UTIs (292 in females; 154 in males); 132 (86%) of the UTIs in males occurred in uncircumcised boys. The mean total cost of managing UTI was 2 times as high in males ($1111) as in females ($542). This higher total cost reflected the higher rate of hospital admission in uncircumcised males with UTIs (27.3%) compared with females (7.5%); mean age at hospitalization for UTI was 2.5 months old for uncircumcised boys and 6.5 months old for girls. In 1996, total cost of managing UTI in uncircumcised males ($155 628) was 10 times higher than for circumcised males ($15 466) despite the fact that uncircumcised males made up only 35.1% of the male patient base in 1996, reflecting the more frequent occurrence of UTI in uncircumcised males (132 episodes) than in circumcised males (22 episodes), and the larger number of hospital admissions in uncircumcised males (38) than in circumcised males (4). The incidence of UTI in the first year of life was 1:47 (2.15%) in uncircumcised males, 1:455 (.22%) in circumcised males, and 1:49 (2. 05%) in females. The odds ratio of UTI in uncircumcised:circumcised males was 9.1:1.",
            "output": [
                "Does newborn circumcision decrease incidence and costs of urinary tract infections during the first year of life?"
            ]
        },
        {
            "id": "task847-745c3edb01624bf298614c33e46246e3",
            "input": "Magnetic fields have been shown to affect cell proliferation and growth factor expression in cultured cells. Although the activation of endorphin systems is a recurring motif among the biological events elicited by magnetic fields, compelling evidence indicating that magnetic fields may modulate opioid gene expression is still lacking. We therefore investigated whether extremely low frequency (ELF) pulsed magnetic fields (PMF) may affect opioid peptide gene expression and the signaling pathways controlling opioid peptide gene transcription in the adult ventricular myocyte, a cell type behaving both as a target and as a source for opioid peptides.', 'Prodynorphin gene expression was investigated in adult rat myocytes exposed to PMF by the aid of RNase protection and nuclear run-off transcription assays. In PMF-exposed nuclei, nuclear protein kinase C (PKC) activity was followed by measuring the phosphorylation rate of the acrylodan-labeled MARCKS peptide. The effect of PMF on the subcellular distribution of different PKC isozymes was assessed by immunoblotting. A radioimmunoassay procedure coupled to reversed-phase high performance liquid chromatography was used to monitor the expression of dynorphin B.', 'Here, we show that PMF enhanced myocardial opioid gene expression and that a direct exposure of isolated myocyte nuclei to PMF markedly enhanced prodynorphin gene transcription, as in the intact cell. The PMF action was mediated by nuclear PKC activation but occurred independently from changes in PKC isozyme expression and enzyme translocation. PMF also led to a marked increase in the synthesis and secretion of dynorphin B.",
            "output": [
                "Do elf-pulsed magnetic fields modulate opioid peptide gene expression in myocardial cells?"
            ]
        },
        {
            "id": "task847-e3360614b68e4dadab2072b97380527f",
            "input": "Three-year colonoscopic surveillance after initial polypectomy may not be required for all patients. Those with multiple baseline polyps and large adenomas, implicated as predictors of colon cancer, merit close observation. Conversely, patients with single small adenomas may be subjected to early endoscopic surveillance unnecessarily.', 'From our Adenoma Registry we evaluated patient and adenoma characteristics in 697 patients. All had an adenoma recurrence within 3 years of a positive baseline colonoscopy. Potential risk factors studied were age, gender, number of adenomas, size of largest adenoma and histology. We defined a significant outcome as size of 1 cm or greater, tubulovillous or villous histology, high-grade dysplasia, carcinoma in situ, invasive cancer, or 4 or more adenomas.', 'Having 3 or more adenomas on initial colonoscopy with at least 1 measuring 1 cm or larger greatly increased the chance of a significant finding on the first surveillance colonoscopy. Conversely, patients with 1 or 2 adenomas all measuring less than 1 cm were at extremely low risk of an important outcome within 3 years.",
            "output": [
                "Are adenoma size and number predictive of adenoma recurrence : implications for surveillance colonoscopy?"
            ]
        },
        {
            "id": "task847-2abc4bb3306a4c37b75e6a6cdff4416c",
            "input": "Although estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanism for this benefit remains unclear. Because nitric oxide (NO) is considered an important endothelium-derived relaxing factor and may function to protect blood vessels against atherosclerotic development, we investigated the acute effects of physiological levels of estrogen on NO release from human internal thoracic artery endothelia and human arterial endothelia in culture.', 'We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase activity in human endothelial cells by acting on a cell-surface receptor. NO release was measured in real time with an amperometric probe. 17beta-Estradiol exposure to internal thoracic artery endothelia and human arterial endothelia in culture stimulated NO release within seconds in a concentration-dependent manner. 17beta-Estradiol conjugated to bovine serum albumin also stimulated NO release, suggesting action through a cell-surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized this action. We further showed with the use of dual emission microfluorometry that 17beta-estradiol-stimulated release of endothelial NO was dependent on the initial stimulation of intracellular calcium transients.",
            "output": [
                "Do cell-surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia?"
            ]
        },
        {
            "id": "task847-ea3cef3c66074bc596d75707a1f1df86",
            "input": "The aim of the present study was to investigate the effects of inulin on calcium metabolism. The study consisted of two separate parts both of which had a randomized two-period cross-over design.', \"Fifteen young healthy women volunteered to participate in this study. During the first part of the study, cheese containing 210 mg of calcium, either with 15 g of inulin or without any inulin, was ingested at breakfast, and in the second part, 210 mg of calcium as a supplement, either with 15 g inulin or without inulin, was ingested. The whole day's diet was standardized. Before breakfast, and 2, 4, 6 and 8 h after breakfast, a blood sample was taken, and intact parathyroid hormone (iPTH), ionized calcium (iCa) and total calcium were measured. Urine was collected throughout the day, and the 8-, 12- and 24-hour calcium excretion was calculated.\", 'The iPTH or iCa concentration curves (AUCs) did not differ over 8 h, whether or not inulin was consumed at breakfast. The postload urinary calcium excretion was not affected by the inulin.",
            "output": [
                "Does addition of inulin to breakfast acutely affect serum ionized calcium and parathyroid hormone concentrations?"
            ]
        },
        {
            "id": "task847-9783183e49064b018d7d8b5b374758f0",
            "input": "Incomplete mitral leaflet coaptation during acute left ventricular ischemia is associated with end-diastolic mitral annular dilatation and ischemic mitral regurgitation. Annular rings were implanted in sheep to investigate whether annular reduction alone is sufficient to prevent mitral regurgitation during acute posterolateral left ventricular ischemia.', 'Radiopaque markers were inserted around the mitral anulus, on papillary muscle tips, and on the central meridian of both mitral leaflets in three groups of sheep: control (n = 5), Physio ring (n = 5) (Baxter Cardiovascular Div, Santa Ana, Calif), and Duran ring (n = 6) (Medtronic Heart Valve Div, Minneapolis, Minn). After 8 +/- 1 days, animals were studied with biplane videofluoroscopy before and during left ventricular ischemia. Annular area was calculated from 3-dimensional marker coordinates and coaptation defined as minimal distance between leaflet edge markers.', 'Before ischemia, leaflet coaptation occurred just after end-diastole in all groups (control 17 +/- 41, Duran 33 +/- 30, Physio 33 +/- 24 ms, mean +/- SD, P >.2 by analysis of variance). During ischemia, regurgitation was detected in all control animals, and leaflet coaptation was delayed to 88 +/- 8 ms after end-diastole (P =.02 vs preischemia). This was associated with increased end-diastolic annular area (8.0 +/- 0.9 vs 6.7 +/- 0.6 cm(2), P =.004) and septal-lateral annular diameter (2.9 +/- 0.1 vs 2.5 +/- 0.1 cm, P =.02). Mitral regurgitation did not develop in Duran or Physio sheep, time to coaptation was unchanged (Duran 25 +/- 25 ms, Physio 30 +/- 48 ms [both P >.2 vs preischemia]), and annular area remained fixed.",
            "output": [
                "Does ring annuloplasty prevent delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia?"
            ]
        },
        {
            "id": "task847-2faea8244fcb4847a7bf6820d9370f31",
            "input": "The treatment of choice for aortic valve insufficiency due to root dilatation has become root replacement with aortic valve sparing. However, root replacement with a synthetic graft may result in altered valve stresses. The purpose of this study was to compare the stress/strain patterns in the spared aortic valve in different root replacement procedures by means of finite element modeling.', 'Our finite element model of the normal human root and valve was modified to simulate and evaluate three surgical techniques: (1) \"cylindrical\" graft sutured below the valve at the anulus, (2) \"tailored\" graft sutured just above the valve, and (3) \"pseudosinus\" graft, tailored and sutured below the valve at the anulus. Simulated diastolic pressures were applied, and stresses and strains were calculated for the valve, root, and graft. Leaflet coaptation was also quantified.', 'All three root replacement models demonstrated significantly altered leaflet stress patterns as compared with normal patterns. The cylindrical model showed the greatest increases in stress (16%-173%) and strain (10%-98%), followed by the tailored model (stress +10%-157%, strain +9%-36%). The pseudosinus model showed the smallest increase in stress (9%-28%) and strain (2%-31%), and leaflet coaptation was closest to normal.",
            "output": [
                "Is re-creation of sinuses important for sparing the aortic valve : a finite element study?"
            ]
        },
        {
            "id": "task847-874db784dffd47a3956884eee4ae9c7f",
            "input": "Recently, we developed a new method to measure collateral blood flow in rats: splenorenal shunt (SRS) blood flow (BF). The aims were to evaluate the reproducibility of SRSBF measurement in different models of portal hypertension, and to investigate the ability of SRSBF to disclose pharmacological changes.', 'Hemodynamics were determined in anesthetized rats with secondary biliary, CCl4 or DMNA cirrhosis and portal vein ligation (PVL) under baseline and pharmacological (octreotide, vapreotide) conditions. The main measurements performed were: SRSBF by the transit time ultrasound (TTU) method and % portosystemic shunts (PSS) by the microsphere method.', 'SRSBF was 6 to 10 times higher in portal hypertensive rats and was similar in the different models of cirrhosis but was higher in portal vein ligated rats than in cirrhotic rats (1.1+/-0.7 vs 0.6+/-0.7 ml x min(-1) x 100 g(-1), p=0.01). SRSBF was correlated with mesenteric %PSS (r=0.61, p<0.01), splenic %PSS (r=0.54, p<0.05), portal pressure (r= 0.32, p<0.05) and the area of liver fibrosis (r=0.33, p<0.05). Octreotide significantly decreased SRSBF (-23+/-20%, p<0.01 vs placebo: -6+/-8%, NS). Vapreotide significantly decreased SRSBF but not mesenteric or splenic %PSS compared to placebo. The variations in SRSBF (-26+/-32%) and in splenic %PSS (0+/-15%) with vapreotide were significantly different (p<0.05) and not correlated (r=-0.1, NS).",
            "output": [
                "Is spleno-renal shunt blood flow an accurate index of collateral circulation in different models of portal hypertension and after pharmacological changes in rats?"
            ]
        },
        {
            "id": "task847-1008302c201d4d05aed1544f65d963a9",
            "input": "Severe alcoholic hepatitis occurs mainly in patients with cirrhosis, and has a high death rate. Corticosteroid therapy has been particularly advocated as reducing mortality in patients with severe histologic lesions. However, identification of these patients is difficult, requiring transvenous liver biopsy. Extracellular matrix serum markers have been proposed as non-invasive diagnostic tools in alcoholic liver disease. The aim of this study was to determine the accuracy of 5 extracellular matrix serum markers, i.e. laminin (Lam), N-terminal peptide of type III procollagen (PIIINP), type I (CI), type III (CIII) and type IV (CIV) collagens in identifying patients with severe histologic alcoholic hepatitis from among those with cirrhosis and suspected alcoholic hepatitis.', \"We studied 80 consecutive patients with alcoholic cirrhosis and clinical suspicion of alcoholic hepatitis referred for transvenous liver biopsy. Clinical severity of alcoholic hepatitis was assessed according to Maddrey's score. Histological severity was scored using the sum of the 3 following items: polynuclear infiltration (0-3); hepatocytes alterations (0-3); Mallory bodies (0-2). According to this score, patients were divided into 3 groups: mild (1-3), moderate (4-6), and severe (7-8) alcoholic hepatitis. Serum levels of the 5 extracellular matrix serum markers were measured at the time of biopsy using radioimmunoassays. Diagnostic value for histologically severe alcoholic hepatitis of the 5 extracellular matrix serum markers was assessed using receiver operating characteristic curves.\", \"Histological alcoholic hepatitis was present in 67 patients (mean alcoholic hepatitis score: 3.4+/-2.3). Maddrey's score was 66% sensitive and 69% specific for the diagnosis of severe histologic alcoholic hepatitis. The serum Lam and CIV concentrations were the most accurate in identifying correctly patients with severe histologic alcoholic hepatitis. At a cut-off of 4.1 UI/ml, Lam was 90% sensitive and 77% specific, whereas at a cut-off of 150 ng/ml, CIV was 89% sensitive and 77% specific. Combination of markers did not result in improved diagnostic value.",
            "output": [
                "Are serum laminin and type IV collagen accurate markers of histologically severe alcoholic hepatitis in patients with cirrhosis?"
            ]
        },
        {
            "id": "task847-9ccd57c8180b4989bc7498cee079019d",
            "input": "Cocaine and alcohol are frequently used simultaneously and this combination is associated with enhanced toxicity. We recently showed that active cocaine abusers have a markedly enhanced sensitivity to benzodiazepines. Because both benzodiazepines and alcohol facilitate GABAergic neurotransmission we questioned whether cocaine abusers would also have an enhanced sensitivity to alcohol that could contribute to the toxicity. In this study we compared the effects of alcohol (0.75 g/kg) on regional brain glucose metabolism between cocaine abusers (n = 9) and controls (n = 10) using PET and FDG. Alcohol significantly decreased whole brain metabolism and this effect was greater in controls (26+/-6%) than in abusers (17+/-10%) even though they had equivalent levels of alcohol in plasma. Analysis of the regional measures showed that cocaine abusers had a blunted response to alcohol in limbic regions, cingulate gyrus, medial frontal and orbitofrontal cortices.",
            "output": [
                "Do cocaine abusers show a blunted response to alcohol intoxication in limbic brain regions?"
            ]
        },
        {
            "id": "task847-0647975e66014ca3a07c27df612cc12c",
            "input": "The etiology of interstitial cystitis is unknown. Urine from patients with interstitial cystitis has been shown to inhibit urothelial proliferation through a putative antiproliferative factor and to contain decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) compared to controls. Stretch of detrusor smooth muscle cells is known to stimulate HB-EGF production. Because bladder hydrodistention sometimes alleviates the symptoms of interstitial cystitis, we determined whether the stretch stimulus of hydrodistention alters antiproliferative factor activity and/or HB-EGF in interstitial cystitis urine specimens.', 'Urine was collected immediately before, and 2 to 4 hours and 2 weeks after hydrodistention from 15 patients with symptoms and cystoscopic findings compatible with interstitial cystitis and 13 controls. Hydrodistention was performed with the subject under general or regional anesthesia and bladders were distended to 80 cm. water 3 times. Urinary HB-EGF was measured by enzyme-linked immunosorbent assay and urinary antiproliferative factor activity was determined by measuring 3H-thymidine uptake by normal human bladder urothelial cells.', 'Hydrodistention significantly increased urinary HB-EGF in patients with interstitial cystitis toward normal control values (before distention p = 0.003, 2 weeks after distention p = 0.67). Urine antiproliferative factor activity decreased significantly after hydrodistention in patients with interstitial cystitis. However, antiproliferative factor activity in interstitial cystitis and control specimens was still statistically different 2 weeks after distention (before distention p = 0.0000004, 2 weeks after distention p = 0.04).",
            "output": [
                "Does bladder stretch alter urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis?"
            ]
        },
        {
            "id": "task847-ec86019cee894c71b1f69614d177b328",
            "input": "To investigate whether the association between APOE-epsilon4 and memory decline is modified by baseline cognition and age in a population-based elderly sample.', 'The study sample consisted of 1,243 subjects, 62 to 85 years old, with a Mini-Mental State Examination (MMSE) score between 21 and 30 and known APOE phenotypes. Memory performance was measured with an abbreviated Auditory Verbal Learning Test (AVLT) at baseline and repeated after 3 years (n = 854). Memory decline was defined as a decrease of at least 1 SD from the mean change score on immediate recall (IR), delayed recall (DR), and retention, based on the AVLT.', 'Multivariate logistic regression analyses showed that APOE-epsilon4 is associated with memory decline in cognitively impaired subjects (MMSE score, 21 to 26) (OR for decline on IR adjusted for age, sex, education, and baseline recall score, 3.8; 95% CI, 1.4 to 10.0; adjusted OR for decline on DR, 2.9; 95% CI, 1.2 to 7.0; adjusted OR for decline on retention, 3.3; 95% CI, 1.1 to 10. 1), but not in cognitively normal subjects (MMSE score, 27 to 30) (adjusted OR for decline on IR, 1.1; 95% CI, 0.6 to 2.0; adjusted OR for decline on DR, 1.0; 95% CI, 0.6 to 1.8; adjusted OR for decline on retention, 1.5; 95% CI, 0.7 to 3.0). In particular, cognitively impaired epsilon4 carriers older than 75 years were at high risk of memory decline (adjusted OR for decline on IR, 4.5; 95% CI, 1.4 to 13.8; adjusted OR for decline on DR, 3.6; 95% CI, 1.2 to 10.8; adjusted OR for decline on retention, 6.6; 95% CI, 1.5 to 29.7).",
            "output": [
                "Is aPOE-epsilon4 associated with memory decline in cognitively impaired elderly?"
            ]
        },
        {
            "id": "task847-baecccb1728543bd8f436fa83d016453",
            "input": "Disruptions to intermyocyte coupling have been implicated in arrhythmogenesis and development of conduction disturbances. At present, understanding of the relationship between the microscopic organization of intercellular coupling and the macroscopic spread of impulse in the normal and diseased heart is largely confined to theoretical analyses.', 'The abundance and arrangement of gap junctions, as well as conduction properties, were assessed in terminal crest preparations isolated from the atria of neonate, weanling, and adult rabbits. We report that the connexin composition of terminal crest was uncomplicated, with Cx43 being the most prominent isoform detectable by Western blotting and immunostaining. Terminal crest myocytes showed little change in total Cx43-gap junction per cell during postnatal growth as assessed by stereology. However, marked non-uniformities emerged in the sarcolemmal distribution of Cx43-gap junctions. Cx43-gap junction area at myocyte termini increased 3.5-fold from birth to adulthood. Correlated with this change in Cx43, impulse propagation velocity parallel to the myofiber axis, as assessed by multi-site optical mapping using voltage-sensitive dye (di-4-ANEPPS), increased 2.4-fold. Conversely, the amount of Cx43-gap junctions on myocyte sides, and the conduction velocity transverse to the myofiber axis, remained relatively invariant during maturation. Hence, the increasing electrical anisotropy of maturing terminal crest was wholly accounted for by increases in conductance velocity along the bundle. This increase in longitudinal conduction velocity was correlated with changes in the sarcolemmal pattern, but not the overall density, of Cx43-gap junctions.",
            "output": [
                "Are the rate and anisotropy of impulse propagation in the postnatal terminal crest correlated with remodeling of Cx43 gap junction pattern?"
            ]
        },
        {
            "id": "task847-3e343b5db82c4af08215899ad84cc20d",
            "input": "Hypercontracture is an important mechanism of myocyte death during reperfusion. cGMP modulates the sensitivity of contractile myofilaments to Ca2+, and increasing cGMP concentration during the last minutes of anoxia prevents reoxygenation-induced hypercontracture in isolated cardiomyocytes. The purpose of this study was to determine whether stimulation of particulate guanylyl cyclase with the natriuretic peptide urodilatin, given at the time of reperfusion, reduces myocardial necrosis in the rat heart submitted to transient ischemia.', 'Isolated rat hearts (n = 38) were submitted to either 40 or 60 min of no-flow ischemia and 2 h of reperfusion, and were allocated to receive or not receive 0.05 microM urodilatin during the first 15 min of reperfusion or non-reperfusion treatment.', 'A marked reduction in myocardial cGMP concentration was observed in control hearts during reperfusion after 40 or 60 min of ischemia. Urodilatin significantly attenuated cGMP depletion during initial reperfusion, markedly improved contractile recovery after 40 min of ischemia (P < 0.0309), and reduced reperfusion-induced increase in left ventricular end-diastolic pressure (P = 0.0139), LDH release (P = 0.0263), and contraction band necrosis (P = 0.0179) after 60 min of ischemia. The beneficial effect of urodilatin was reproduced by the membrane permeable cGMP analog 8-Bromo-cGMP.",
            "output": [
                "Does urodilatin limit acute reperfusion injury in the isolated rat heart?"
            ]
        },
        {
            "id": "task847-24401b2101d44b8e82202ad7238cbc22",
            "input": "Diminishing oxidative stress may protect the heart against ischaemia-reperfusion injury by preventing opening of the mitochondrial permeability transition (MPT) pore. The general anaesthetic agent propofol, a free radical scavenger, has been investigated for its effect on the MPT and its cardioprotective action following global and cardioplegic ischaemic arrest.', \"Isolated perfused Wistar rat hearts were subjected to either warm global ischaemia (Langendorff) or cold St. Thomas' cardioplegia (working heart mode) in the presence or absence of propofol. MPT pore opening was determined using [3H]-2-deoxyglucose-6-phosphate ([3H]-DOG-6P) entrapment. The respiratory function of isolated mitochondria was also determined for evidence of oxidative stress.\", 'Propofol (2 micrograms/ml) significantly improved the functional recovery of Langendorff hearts on reperfusion (left ventricular developed pressure from 28.4 +/- 6.2 to 53.3 +/- 7.3 mmHg and left ventricular end diastolic pressure from 52.9 +/- 4.3 to 37.5 +/- 3.9 mmHg). Recovery was also improved in propofol (4 micrograms/ml) treated working hearts following cold cardioplegic arrest. External cardiac work on reperfusion improved from 0.42 +/- 0.05 to 0.60 +/- 0.03 J/s, representing 45-64% of baseline values, when compared to controls (P < 0.05). Propofol inhibited MPT pore opening during reperfusion, [3H]-DOG-6P entrapment being 16.7 vs. 22.5 ratio units in controls (P < 0.05). Mitochondria isolated from non-ischaemic, propofol-treated hearts exhibited increased respiratory chain activity and were less sensitive to calcium-induced MPT pore opening.",
            "output": [
                "Is protection of hearts from reperfusion injury by propofol associated with inhibition of the mitochondrial permeability transition?"
            ]
        },
        {
            "id": "task847-adbace4e4fa6461f82a15113d8061b06",
            "input": "Japanese in-patients with pulmonary tuberculosis and normal liver function receiving treatment with isoniazid and rifampicin (INH + RMP).', 'To elucidate the relationship between N-acetyltransferase 2 (NAT2) genotype and the incidence of isoniazid + rifampicin-induced hepatotoxicity.', 'Prospective study. After NAT2* genotyping, 77 patients were classified into three groups according to their NAT2* genotypes: rapid-type (a homozygote of NAT2*4), intermediate-type (a heterozygote of NAT2*4 and mutant alleles) and slow-type (a combination of mutant alleles). Their biochemical profiles of liver function test were investigated for 3 months to assess the development of serum aminotransferase elevation.', 'Of the 77 patients, 18.2% developed adverse hepatic reaction within the first month of INH + RMP treatment. A significant association was observed between hepatotoxicity and NAT2* genotype: compared with rapid-type, the relative risk was 4.0 (95% CI 1.94-6.06) for intermediate-type and 28.0 (95%CI 26.0-30.0) for slow-type. Especially in slow-type, the incidence of hepatotoxicity and serum aminotransferase elevation was significantly higher than in the other two types.",
            "output": [
                "Does slow N-acetyltransferase 2 genotype affect the incidence of isoniazid and rifampicin-induced hepatotoxicity?"
            ]
        },
        {
            "id": "task847-7c61cc17c1894d04ad685ab7c7f84d4e",
            "input": "We sought to determine whether abciximab therapy at the time of percutaneous coronary intervention (PCI) would favorably affect one-year mortality in patients with diabetes.', 'Diabetics are known to have increased late mortality following PCI.', 'Data from three placebo-controlled trials of PCI, EPIC, EPILOG, and EPISTENT, were pooled. The one-year mortality rate for patients with a clinical diagnosis of diabetes mellitus was compared with the rate for nondiabetic patients treated with either abciximab or placebo.', 'In the 1,462 diabetic patients, abciximab decreased the mortality from 4.5% to 2.5%, p = 0.031, and in the 5,072 nondiabetic patients, from 2.6% to 1.9%, p = 0.099. In patients with the clinical syndrome of insulin resistance--defined as diabetes, hypertension, and obesity--mortality was reduced by abciximab treatment from 5.1% to 2.3%, p = 0.044. The beneficial reduction in mortality with abciximab use in diabetics classified as insulin-requiring was from 8.1% to 4.2%, p = 0.073. Mortality in diabetics who underwent multivessel intervention was reduced from 7.7% to 0.9% with use of abciximab, p = 0.018. In a Cox proportional hazards survival model, the risk ratio for mortality with abciximab use compared with placebo was 0.642 (95% confidence interval 0.458-0.900, p = 0.010).",
            "output": [
                "Does abciximab reduce mortality in diabetics following percutaneous coronary intervention?"
            ]
        },
        {
            "id": "task847-272d685a023744f8a263b53fd42d8d16",
            "input": "All known pathways of ethanol metabolism result in the production of acetaldehyde, a highly reactive compound. Acetaldehyde has been shown to deplete vitamin B6 in chronic alcoholics. It also binds with sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing vascular cytosolic free calcium, peripheral vascular resistance and blood pressure. The aldehyde-binding thiol compound, N-acetyl cysteine, attenuates elevated blood pressure and associated adverse changes in ethanol-induced hypertensive rats. Vitamin B6 supplementation increases the level of endogenous cysteine. Aim of this work was thus to investigate whether a dietary supplementation of vitamin B6 can prevent ethanol-induced hypertension and associated changes in Wistar-Kyoto (WKY) rats.', 'Starting at 7 weeks of age, WKY rats were divided into three groups of six animals each. The control group received a normal vitamin B6 diet (regular chow) and normal drinking water, the ethanol group, the same diet plus 1% ethanol in the drinking water, and the ethanol + vitamin B6 group a high vitamin B6 diet (20 times normal diet) and 1% ethanol in the drinking water. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugate levels were significantly higher in the ethanol group. These rats also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation prevented these changes.",
            "output": [
                "Does dietary vitamin B6 supplementation prevent ethanol-induced hypertension in rats?"
            ]
        },
        {
            "id": "task847-9fdf63485c174026bc2bfaba527b8f24",
            "input": "The anti-inflammatory effect of low-dose radiotherapy (LD-RT) still is not understood. The adhesion of leukocytes to endothelial cells (EC) of the vessel wall is the initial event of tissue invasion, and thus, crucially contributes to the regulation of inflammation. We investigated the influence of LD-RT on the adhesion process in vitro.', 'Isolated peripheral-blood-mononuclear-cells (PBMC) were incubated with an activated murine endothelioma cell-line under shear conditions at 4 degrees C after irradiation with single doses between 0.1 and 10.0 Gy. Adherent cells were counted microscopically and compared to a non-irradiated control. In parallel, viability and expression of adhesion molecules, especially of L-selectin, and lineage-specific markers on the cell surface were determined by dye exclusion and cytofluorometry, respectively. Modulation of adhesion by soluble L-selectin was tested in the adhesion assay.', 'Radiation doses of 0.1-0.5 Gy reduced the adhesion of viable PBMC to EC in vitro by 70% of the control level 4 h after irradiation. Leukocytes showed a marked reduction of L-selectin expression after LD-RT. Soluble L-selectin can inhibit the adhesion of PBMC to EC.",
            "output": [
                "Does low-dose radiotherapy selectively reduce adhesion of peripheral blood mononuclear cells to endothelium in vitro?"
            ]
        },
        {
            "id": "task847-d0776a84677f404283550f4263ded974",
            "input": "Recovery to normal or near normal visual acuity is usual after acute demyelinating optic neuritis, despite the frequent persistence of conduction abnormalities as evidenced by the visual evoked potential (VEP). This raises the possibility that cortical adaptation to a persistently abnormal input contributes to the recovery process. The objective of this study was to investigate the pattern of cerebral response to a simple visual stimulus in recovered patients in comparison to normal subjects.', 'Functional magnetic resonance imaging (fMRI) was used to study the brain activation pattern induced by a periodic monocular 8Hz photic stimulus in seven patients who had recovered from a single episode of acute unilateral optic neuritis, and in seven normal controls. VEPs and structural optic nerve MRI were performed on patients.', 'Stimulation of either eye in controls activated only the occipital visual cortex. However, in patients, stimulation of the recovered eye also induced extensive activation in other areas including the insula-claustrum, lateral temporal and posterior parietal cortices, and thalamus; stimulation of the clinically unaffected eye activated visual cortex and right insula-claustrum only. The volume of extraoccipital activation in patients was strongly correlated with VEP latency (r = 0.71, p = 0.005).",
            "output": [
                "Is recovery from optic neuritis associated with a change in the distribution of cerebral response to visual stimulation : a functional magnetic resonance imaging study?"
            ]
        },
        {
            "id": "task847-6a4cb8d14b2c4139b49e17a7a523a7b1",
            "input": "An intact and fully functional multiprotein DNA replication complex (DNA synthesome) from human as well as from murine mammary carcinoma cells was first isolated and characterized in our laboratory. The human cell synthesome supports the in vitro origin-specific simian virus 40 (SV40) DNA replication reaction in the presence of the viral large T-antigen using a semiconservative mechanism and has been shown to contain all the proteins and enzymes required to support DNA synthesis. We are currently using the DNA synthesome as a unique model for analyzing the mechanism of action of anticancer drugs affecting DNA replication. The purpose of this study was to further investigate the mechanism of action of ara-C using the DNA synthesome isolated from the human breast cancer cell line MDA MB-468.', 'Synthesome-mediated SV40 DNA replication was performed in the presence of various concentrations of ara-CTP (the active metabolite of ara-C) and the types of daughter DNA molecules produced were analyzed lusing neutral and alkaline gel electrophoresis. We also examined the effect of ara-C on intact MDA MB-468 cell DNA synthesis and on cell proliferation. In addition, we studied the effect of ara-CTP on the activity of some of the synthesome target proteins (the DNA polymerases alpha and delta).', 'Full-length daughter DNA molecules were obtained in the presence of low concentrations of ara-CTP while at higher concentrations, there was an inhibition of full-length daughter DNA synthesis. The findings suggest that specifically the initiation phase of DNA synthesis was inhibited by ara-CTP since the production of the short Okazaki fragments was suppressed at all concentrations of the drug above 10 microM. In addition, it was found that the IC50 of ara-CTP for inhibition of synthesome-mediated in vitro DNA replication was comparable to that required to inhibit intact cell DNA synthesis. Further experimentation has shown that ara-CTP preferentially inhibits the activity of the synthesome-associated DNA polymerase alpha enzyme while the DNA polymerase delta seems to be resistant to the inhibitory effect of that drug.",
            "output": [
                "Does ara-C affect formation of cancer cell DNA synthesome replication intermediates?"
            ]
        },
        {
            "id": "task847-589a19ddb1a244038a11df7d21de0279",
            "input": "To investigate the early stages in the formation of bony spurs in relation to normal enthesis development.', \"Histologic sections of rat Achilles tendons, stained with toluidine blue or Masson's trichrome, were examined in animals ranging from 2 weeks to 1 year of age. Further material prepared for immunohistochemistry was labeled with monoclonal antibodies for laminin and type IV collagen to highlight the presence of small blood vessels at the enthesis. Sections of small spurs from the Achilles tendons of elderly humans were also examined for comparison.\", 'As a part of normal development, bone grows into the Achilles tendon as the calcaneus enlarges. Ossification is preceded by vascular invasion, which occurs along rows of enthesis fibrocartilage cells. Small bony spurs develop when ossification at one point on the enthesis outstrips that on either side.",
            "output": [
                "Does the mechanism of formation of bony spur ( enthesophytes ) in the achilles tendon?"
            ]
        },
        {
            "id": "task847-1c7e4160e56c487399ce7ea0ec5445ec",
            "input": "Increased oxidative stress and myocyte apoptosis co-exist in the remote non-infarcted myocardium (RM) following a large myocardial infarction. We proposed that these phenomena are causally related.', 'On day 3 after induction of myocardial infarction, Sprague-Dawley rats were randomized to receive probucol and pyrrolidine dithiocarbamate (MI-T), or vehicle only (MI) for 7 weeks. Control rats (C) received vehicle. At 7 weeks, lipidperoxidation within the RM was assessed by measuring thiobarbituric acid reactive substances, which were significantly increased in MI vs. C, while MI-T was not different from C. There was a significant increase in cardiac myocytes positive for in situ TdT-UTP nick-end labeling within the RM in MI vs. C, which was inhibited in MI-T. Furthermore, internucleosomal DNA fragmentation was clearly demonstrated on agarose gels from RM in the MI group, while it was much less apparent on gels from RM in the C and MI-T groups. Western blot analysis showed a significant increase in p53, Bax and caspase-3 protein expression within the RM of MI vs. C, all of which were inhibited in the MI-T group. Furthermore, there was evidence for an increase in caspase-3 activity within the RM from MI vs. C, which was normalized in the MI-T group.",
            "output": [
                "Do antioxidants attenuate myocyte apoptosis in the remote non-infarcted myocardium following large myocardial infarction?"
            ]
        },
        {
            "id": "task847-31fa68495bbc4339a4dcc95d80b0937d",
            "input": "Apoptosis of cardiomyocytes may contribute to ischemia-reperfusion injury. The role of nitric oxide (NO) in apoptosis is controversial. Therefore, we investigated the effect of NO synthase inhibition on apoptosis of cardiomyocytes during ischemia and reperfusion and elucidated the underlying mechanisms.', 'Isolated perfused rat hearts (n = 6/group) were subjected to ischemia (30 min) and reperfusion (30 min) in the presence or absence of the NO synthase inhibitor NG-mono-methyl-L-arginine. Reperfusion induced cardiomyocyte apoptosis as assessed by immunohistochemistry (TUNEL-staining) and the demonstration of the typical DNA laddering. Apoptosis during reperfusion was associated with the cleavage of caspase-3, the final down-stream executioner caspase, whereas the protein levels of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax were unchanged. Inhibition of the NO synthase drastically increased ischemia and reperfusion-induced apoptosis of cardiomyocytes. Moreover, the NO synthase inhibitor enhanced the activation of caspase-3, suggesting that NO interferes with the activation of caspases in ischemia-reperfusion.",
            "output": [
                "Does inhibition of endogenous nitric oxide synthase potentiate ischemia-reperfusion-induced myocardial apoptosis via a caspase-3 dependent pathway?"
            ]
        },
        {
            "id": "task847-899434d1c8ec466fa1ae42f9a3f2466e",
            "input": "It has been demonstrated that tumor necrosis factor-alpha (TNF alpha) induces apoptosis in cardiac myocytes. However, its mechanism of action is still not well understood. In the present study, we hypothesized that TNF alpha induces myocardial apoptosis by induction of inducible nitric oxide synthase (iNOS).', 'Neonatal cardiac myocytes were isolated from iNOS (-/-) mutant and C57BL6 wild type mice. Cells were cultured for 3 days before treatment with an NO donor or TNF alpha. Following treatment with S-nitroso-N-acetyl-penicillamine (SNAP) or TNF-alpha, cells were tested for apoptosis by terminal deoxynucleotidyl transfer-mediated end labeling (TUNEL) staining and cell death detection ELISA. NO production was measured by nitrite concentration in the culture medium. Cardiomyocyte expression of iNOS and TNF type 1 receptor (TNFR1) mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR).', 'SNAP (0.01-100 microM) induced apoptosis of cardiac myocytes in a concentration-dependent manner in the wild type mice (n = 5, P < 0.01). TNFR1 mRNA was expressed in neonatal cardiomyocytes from both wild type and iNOS (-/-) mutant mice. TNF alpha induced a concentration-dependent increase in iNOS mRNA expression and nitrite production as well as significant apoptosis of cardiomyocytes in the wild type mice (n = 4, P < 0.01). However, without iNOS expression, the apoptotic effects of TNF-alpha were significantly attenuated in cardiomyocytes from iNOS (-/-) mutant mice (n = 4, P < 0.05).",
            "output": [
                "Does tumor necrosis factor-alpha induce apoptosis via inducible nitric oxide synthase in neonatal mouse cardiomyocytes?"
            ]
        },
        {
            "id": "task847-7821b9638a2840d4b1ad9c37730a1af2",
            "input": "Blood-epithelial barriers have been described in the testis and epididymis, but the possibility of such barriers in other regions of the male genitourinary tract has received little investigation. The purpose of this study was to use in vivo micro-puncture to determine if the blood-epithelial barrier exists in the rat ventral prostate. In addition, using a model of prostatic inflammation, we sought to examine the effect of inflammation on the passage of blood borne molecules and leukocytes into the prostatic ductal lumen.', 'Adult Sprague-Dawley rats were divided into two groups, control and 24-hour lipopolysaccharide (LPS)-induced inflammation. Both groups were subjected to vascular infusion of radiolabeled 3H dextran, 14C urea, and 3H water. Contemporaneous in vivo micropuncture sampling of prostatic ductal fluid (DF) and arterial blood occurred at multiple time points over 120 minutes. Transepithelial movement of radiolabeled compounds at each sampling time point was quantified by the expression of DF isotope concentrations as a percentage of serum isotope concentrations at that time point. Histology of representative specimens of control and inflamed prostates was used to confirm the inflammatory response and to examine for the presence of leukocytes into the ductal lumen.', \"The transepithelial movement of radiolabeled compounds from blood to prostatic lumen varied in direct relationship to the compound's molecular weight. 3H-water (MW = 18) movement into the ductal lumina was relatively rapid plateauing at 70-80% of serum values. 14C urea (MW = 60) achieved intermediate penetration into ductal fluid (50-60% of serum values) and 3H dextran (MW = 2 x 106) was essentially excluded from entry (<2% of serum). These results were not altered by LPS-induced inflammation. Histology revealed a diffuse leukocyte infiltrate in the inflamed prostatic interstitium, but penetration of inflammatory cells into the ductal lumen was very restricted.",
            "output": [
                "Does a blood-prostate barrier restrict cell and molecular movement across the rat ventral prostate epithelium?"
            ]
        },
        {
            "id": "task847-5d026fe86e254a16bb540a218d1f0305",
            "input": "We examined whether heparin-coated (HC) circuits can improve the operative results in patients with chronic renal insufficiency.', 'Elective cardiac surgery was performed in 24 patients with a serum creatinine (Cr) level of at least 1.5 mg/dl. Uncoated circuits were used in 12 patients, and HC circuits were used in 12 patients. The results of surgery were compared between the two groups.', 'The mean preoperative Cr concentration was significantly higher in the HC group (2.3 vs 1.8 mg/dl). The heparin doses, protamine dose, and activated clotting times were significantly lower in the HC group. The mean blood loss was also less, although this difference was not significant. The postoperative increase in the Cr level was small in the HC group (2.3-->2.5 mg/dl) compared to that in the noncoated group (1.8-->2.3 mg/dl). Postoperative dialysis was not required in the 5 patients in the HC group with a preoperative Cr clearance less than 20 ml/min.",
            "output": [
                "Do heparin-coated circuits prevent renal dysfunction after open heart surgery?"
            ]
        },
        {
            "id": "task847-354a5c5544cc45a2948a9cbadbefe093",
            "input": "Sildenafil (Viagra), an oral treatment for erectile dysfunction, has proved popular since its introduction in 1998. However, not all patients respond to this form of therapy. Consequently, this study investigated the efficacy of intracavernous alprostadil alfadex (EDEX/VIRIDAL) treatment in patients not responding to sildenafil.', 'In an open-label, multicenter study, patients with erectile dysfunction were treated with sildenafil for 4 weeks. The initial dose was 50 mg, which was increased to 100 mg if no response was achieved. Patients not responding to treatment, measured using the International Index of Erectile Function (IIEF) questionnaire, entered an alprostadil alfadex in-office titration phase, to determine the optimal dose, up to 40 microgram. A 6-week alprostadil alfadex at-home treatment phase followed.', 'In 67 patients who did not respond satisfactorily to sildenafil, the alprostadil alfadex at-home therapy resulted in improvements in questions 3 and 4 of the IIEF in 60 (89.6%) and 57 (85.1%) patients, respectively. The mean improvement in IIEF score for these patients was 2.75 and 2.63 for questions 3 and 4, respectively. The most common side effect was penile pain in 25 (29. 4%) of 85 patients treated with alprostadil alfadex in-office and at home.",
            "output": [
                "Is intracavernous alprostadil alfadex ( EDEX/VIRIDAL ) effective and safe in patients with erectile dysfunction after failing sildenafil ( Viagra )?"
            ]
        },
        {
            "id": "task847-748ef0a198564fd1b8d4712f1f2881eb",
            "input": "To study the pathophysiological importance of changes in insulin sensitivity and islet function over time for alterations in glucose tolerance in a randomly selected large group of non-diabetic women aged 57-59 years over a 3-year period.', 'At baseline and at the 3-year follow-up, glucose tolerance (WHO 75 g oral glucose), insulin sensitivity (euglycaemic, hyperinsulinaemic clamp) and insulin and glucagon secretion (2 to 5-min responses to 5 g i.v. arginine at fasting, 14 and > 25 mmol/l glucose) were measured.', 'At baseline, women with impaired glucose tolerance (IGT, n = 28) had lower insulin sensitivity (p = 0.048) than normal women (NGT, n = 58). The arginine-induced insulin responses (AIR) were inversely associated with insulin sensitivity (r > or = -0.55, p < 0.001). When related to the 3-year follow-up, the baseline product of AIR at 14 mmol/l glucose times insulin sensitivity, insulin effect index (IE) (r = -0.40, p < 0.001) and the arginine-induced glucagon response at 14 mmol/l glucose (AGR, r = 0.28, p = 0.009) both correlated with follow-up 2-h glucose. In a multiple regression model, baseline 2-h glucose, insulin effect index and arginine-induced glucagon response independently predicted 2-h glucose at follow-up (total r = 0.668, p < 0.001). Furthermore, delta insulin sensitivity (i. e. follow-up minus baseline) correlated with delta insulin secretion (r = -0.30, p = 0.006), whereas delta glucagon secretion correlated with delta2-h glucose (r = 0.30, p = 0.006) over the 3 years. In a multiple regression, alterations in 2-h glucose over the 3 years were independently determined by changes in fasting insulin and glucagon secretion (r = 0.424, p < 0.001).",
            "output": [
                "Is glucose intolerance predicted by low insulin secretion and high glucagon secretion : outcome of a prospective study in postmenopausal Caucasian women?"
            ]
        },
        {
            "id": "task847-5dda11cfcdf9486abc09630ad4aabd90",
            "input": "In obese French Caucasian subjects we previously described a silent UCP3 Tyr99Tyr mutation, associated with body mass index. We hypothesised that an unknown polymorphism in the vicinity of the gene could contribute to obesity.', 'Morbidly obese subjects were screened for mutations in 1 kb upstream from the UCP3 gene. Association studies were done between a variant and obesity in 401 morbidly obese and 231 control subjects.', 'We detected three rare genetic variants and one polymorphism: a +5 G-->A in exon 1, a -155 C-->T, a -439 A insertion and a -55 C-->T located 6 bp from the putative TATA box. This variant was in linkage disequilibrium with the Tyr99Tyr polymorphism. Frequencies of the variant allele at the -55 locus were similar in the obese and control groups (0.23 vs 0.21). The -55 polymorphism was associated with BMI in the obese group (p = 0.0031): BMI was higher in TT than in CC or CT patients. Likewise control subjects with a TT genotype had a higher BMI (p = 0.03). In the obese group, homozygosity for this variant is a risk factor for high BMI (odds ratio: 1:75, p = 0.02). Obese patients were divided into tertiles according to physical activity. In the group with a wild C/C genotype, BMI was negatively associated with physical activity (p = 0.015).",
            "output": [
                "Is a genetic variation in the 5 ' flanking region of the UCP3 gene associated with body mass index in humans in interaction with physical activity?"
            ]
        },
        {
            "id": "task847-54e9dd20a50c4f5cb0e9db185783842a",
            "input": "Lipopolysaccharide (LPS) is closely associated with the development of infection-induced deleterious pulmonary reactions. In this study, we investigated the enhancement effects of LPS on tachykinin-mediated plasma exudation in the lungs of guinea pigs. The role of oxidants was also explored.', 'Intravenous LPS (100 mu kg-1) or its vehicle was administered 0 to 3 hours prior to bilateral electrical or sham stimulation of the cervical vagus nerves in animals anesthetized with urethane and artificially ventilated. Plasma exudation into the lungs was assessed by measurement of extravasated 125I-albumin which had been intravenously administered before stimulation.', 'The plasma exudation in the lungs increased after bilateral cervical vagal stimulation. LPS alone did not induce significant plasma exudation. The vagally-mediated plasma exudation was enhanced by LPS with the peak effect 1 hour after LPS administration. LPS also enhanced exogenous substance P (10(-8) mol kg-1, i.v.)-induced plasma exudation. The vagally-induced plasma exudation was abolished by a specific neurokinin-1 (NK-1) receptor antagonist, L-732,138. The LPS-induced enhancement response was also attenuated by L-732,138. The vagally-induced plasma exudation was not affected by superoxide dismutase (SOD, 5000 U kg-1, i.p.) pretreatment. However, SOD significantly inhibited the LPS-enhanced neurogenic plasma leakage. The LPS-induced enhancement was not completely abolished by either L-732,138 or SOD pretreatment alone, but by a combination of both.",
            "output": [
                "Does endotoxemia augment neurogenic plasma exudation in guinea pig lungs?"
            ]
        },
        {
            "id": "task847-75caefdbf3c34a968ccf9a07f2f2091f",
            "input": "The aim of this study was the measurement of maternal serum levels of M-CSF throughout pregnancy, in a low risk obstetrical population, to examine the relationship of M-CSF and pregnancy outcome.', 'Maternal serum was obtained at various stages of pregnancy and post partum, M-CSF levels were measured by ELISA, pertinent clinical data tabulated, and pregnancy outcome was determined.', 'In 564 pregnancies studied, 22% of 260 nulliparous pregnancies and 10% of 304 multiparous pregnancies were hypertensive. Preeclampsia occurred in 1.5% of nulliparous and in 1% of the multiparous women. In apparently normal pregnancies with good outcome, M-CSF levels rose throughout pregnancy. No cases of preeclampsia occurred if maternal serum M-CSF levels increased more than 100% throughout pregnancy.",
            "output": [
                "Are maternal serum levels of macrophage colony-stimulating factor associated with adverse pregnancy outcome?"
            ]
        },
        {
            "id": "task847-a0cabf786beb4955914b31d891391a9f",
            "input": "Interleukin-8 (IL-8), a CXC chemokine that induces the migration and proliferation of endothelial cells and smooth muscle cells, is a potent angiogenic factor that may play a role in atherosclerosis. Previously, IL-8 has been reported in atherosclerotic lesions and circulating macrophages from patients with atherosclerosis. Therefore, we sought to determine whether IL-8 plays a role in mediating angiogenic activity in atherosclerosis.', 'Homogenates from 16 patients undergoing directional coronary atherectomy (DCA) and control samples from the internal mammary artery (IMA) of 7 patients undergoing bypass graft surgery were assessed for IL-8 content by specific ELISA, immunohistochemistry, and in situ hybridization for IL-8 mRNA. The contribution of IL-8 to net angiogenic activity was assessed using the rat cornea micropocket assay and cultured cells. IL-8 expression was significantly elevated in DCA samples compared with IMA samples (1.71+/-0.6 versus 0.05+/-0.03 ng/mg of total protein; P<0.01). Positive immunolocalization of IL-8 was found exclusively in DCA tissue sections, and it correlated with the presence of factor VIII-related antigen. In situ reverse transcriptase polymerase chain reaction revealed the expression of IL-8 mRNA in DCA tissue. Corneal neovascular response, defined by ingrowth of capillary sprouts toward the implant, was markedly positive with DCA pellets, but no constitutive vessel ingrowth was seen with IMA specimens. Neutralizing IL-8 attenuated both the in vivo corneal neovascular response and the in vitro proliferation of cultured cells.",
            "output": [
                "Is iL-8 an angiogenic factor in human coronary atherectomy tissue?"
            ]
        },
        {
            "id": "task847-6c410870d0e546348458dbd23ec4416b",
            "input": "Rapid ventricular pacing produces a reliable model of heart failure. Cessation after 4 weeks of rapid ventricular pacing results in rapid normalization of left ventricular function, but the left ventricle remains persistently dilated. We present novel data that show that prolonged rapid ventricular pacing (10 weeks) creates a model of chronic left ventricular dysfunction.', 'In 9 dogs undergoing 10 weeks of rapid ventricular pacing, left ventricular function and volumes were serially assessed by using 2-dimensional echocardiography and pressure-volume analysis for 12 weeks after cessation of pacing.', 'Increased end-diastolic volume and decreased systolic and diastolic function were seen at the end of pacing. By 2 weeks of recovery from rapid ventricular pacing, end-diastolic volume and ejection fraction were partially recovered but did not improve further thereafter. Load-independent and load-sensitive indices of function obtained by pressure-volume analysis at 8 and 12 weeks of recovery confirmed a persistence of both systolic and diastolic dysfunction. In addition, left ventricular mass increased with pacing and remained elevated at 8 and 12 weeks of recovery. Four of these dogs studied at 6 months of recovery showed similar left ventricular abnormalities.",
            "output": [
                "Does ten weeks of rapid ventricular pacing create a long-term model of left ventricular dysfunction?"
            ]
        },
        {
            "id": "task847-4ceab22b315d433bb105cfe80fd9f423",
            "input": "A reversible contractile dysfunction without necrosis after transient myocardial ischemia has been termed stunning. The molecular mechanisms underlying this phenomenon are only now beginning to be unraveled. It is conceivable that the expression of early-response genes may play a crucial role in stunning.', 'The expression of HSP-70, c-jun, and GRP-94 was investigated in a chronically instrumented dog model (n = 9). The left anterior descending coronary artery was occluded temporarily for 10 minutes after the animals had fully recovered from instrumentation. The wall thickening fraction was measured in the left anterior descending coronary artery and the nonischemic ramus circumflex of the left coronary artery-perfused region. When the wall thickening fraction of the left anterior descending coronary artery had recovered to 50% of preocclusion values, tissue samples were obtained from the areas perfused by the left anterior descending coronary artery and the nonischemic ramus circumflex of the left coronary artery.', 'The messenger RNA of HSP-70 was increased to 214% +/- 26% in the area perfused by the left anterior descending artery compared with that perfused by the nonischemic ramus circumflex of the left coronary artery. There was no difference in the messenger RNA of GRP-94. The HSP-70 content was elevated to 130% +/- 14% in the left anterior descending artery compared with the area perfused by the ramus circumflex of the left coronary artery, and the c-jun protein content was 70% +/- 25% higher in the ischemic area compared with the control area.",
            "output": [
                "Are the early response genes c-jun and HSP-70 induced in regional cardiac stunning in conscious mammals?"
            ]
        },
        {
            "id": "task847-bd360629e5ff43efa43a99bab0072188",
            "input": "Our objective was to determine whether paclitaxel-induced apoptosis in human lung cancer cells is Fas dependent.', 'Human lung cancer cell lines were evaluated for morphologic evidence of apoptosis, DNA fragmentation (TUNEL positivity), and caspase-3 activation after paclitaxel treatment. Human lung adenocarcinoma, squamous cell carcinoma, undifferentiated lung carcinoma, and bronchoalveolar carcinoma cell lines were each cultured in 10 micromol/L paclitaxel.', 'After 24 hours of culture in paclitaxel, a 22% to 69% increase in the number of apoptotic cells was evident by means of methylene blue-azure A-eosin staining with characteristic blebbing and nuclear condensation. TUNEL assay also confirmed an increase of 19.9% to 73.0% of cells with nuclear fragmentation. Caspase-3 activity, assayed by Z-DEVD cleavage, increased from 20% to 215% (P <.05). ZB4, an antagonistic anti-Fas antibody, did not block paclitaxel induction of caspase-3 activity (155.8 vs 165.8 U, not significant). Apoptotic morphologic changes were inhibited in cells cultured in the presence of paclitaxel and Ac-DEVD-CHO, a caspase-3 inhibitor.",
            "output": [
                "Is paclitaxel-induced apoptosis in non-small cell lung cancer cell lines associated with increased caspase-3 activity?"
            ]
        },
        {
            "id": "task847-31069d1970704356ab10b1dc797a7c4d",
            "input": "The present study was conducted to determine whether preservation of the right atrial appendage lessens the decrease of plasma atrial natriuretic peptide levels after the maze procedure and whether the increase of plasma atrial natriuretic peptides improves the ability of the kidneys to excrete the fluid load after the operation.', 'We evaluated 42 patients who underwent the maze procedure. The right atrial appendage was preserved in 22 patients but not in 20. Blood samples were obtained before and after the operation for measurement of atrial natriuretic peptides. To evaluate the influence of atrial natriuretic peptides on the ability of the kidneys, we also measured body weight, fluid balance, and the doses of furosemide and dopamine administered after the operation.', 'The restoration to sinus rhythm at 1 month after was comparable in the two groups. Plasma atrial natriuretic peptide levels significantly increased after the operation in patients in whom the right atrial appendage was preserved (1 day after: 23.4 +/- 17.8 vs 3 days after: 42.7 +/- 23.6 and 7 days after: 36.3 +/- 23.7 pg/mL, P <.05) but not in patients in whom the right atrial appendage was not preserved (1 day after: 20.0 +/- 19.6, 3 days after: 28.5 +/- 19.3, and 7 days after: 23.0 +/- 16.1 pg/mL). Furthermore, plasma atrial natriuretic peptide levels were significantly lower in patients in whom the right atrial appendage was not preserved than in patients in whom the right atrial appendage was preserved at 3 and 7 days after the operation. The fluid balance during the first 7 days of the postoperative period was comparable in the two groups, although the total dose of dopamine used in the same period was significantly smaller in patients in whom the right atrial appendage was preserved than in patients in whom the right atrial appendage was not preserved (155.3 +/- 119.0 vs 244.9 +/- 129.0 microg/kg, P <.05).",
            "output": [
                "Does preservation of the right atrial appendage improve reduced plasma atrial natriuretic peptide levels after the maze procedure?"
            ]
        },
        {
            "id": "task847-526e4b0696c34cc781d9789b6929633d",
            "input": "Cholangiocarcinoma is a feared complication of primary sclerosing cholangitis (PSC). Neoplastic bile duct strictures may be difficult to differentiate cholangiographically from the non-neoplastic bile duct irregularities characteristic of this disorder, and the diagnosis of cholangiocarcinoma may be difficult to establish with certainty, even in tissue samples. Thus, new methods which can improve the diagnostic accuracy of cholangiocarcinoma in PSC are needed.', 'We investigated the occurrence of K-ras codon 12 and 13 mutations, p53 protein accumulation, and Ki-67 expression in tumor tissue from PSC patients (n=33) who had developed cholangiocarcinoma, using bile duct specimens exised at liver transplantation of PSC patients without cholangiocarcinoma (n=15) as controls', 'K-ras mutations were present in 11 (33%) of the cholangiocarcinoma samples and significantly more frequent in females. Nine tumors carried a codon 12 mutation, and 2 had a codon 13 mutation. The most frequent substitutions in codon 12 were GGT-->GAT (n=5) and GGT-->TGT (n=3). None of the control bile ducts had K-ras mutations. p53 protein was accumulated in 10 (31%) of the tumors, as opposed to negative findings in all the control samples. Sixteen (48%) tumors revealed either K-ras mutation or p53 accumulation. Ki-67 positivity was significantly higher in cholangiocarcinomas than in the non-neoplastic bile ducts (median 29% vs 12%, respectively; p=0.011).",
            "output": [
                "Are cholangiocarcinoma in primary sclerosing cholangitis : K-ras mutations and Tp53 dysfunction implicated in the neoplastic development?"
            ]
        },
        {
            "id": "task847-7455e5cc622849debf08844820c94c5c",
            "input": "Depletion of trabecular meshwork cell numbers is a feature of the outflow system in aging and in primary open-angle glaucoma. It is possible that migration stimulated by factors present in aqueous humor may contribute to the cell loss. This investigation assessed the chemoattractant potential of glaucomatous and nonglaucomatous human aqueous humor and fibronectin, one of its constituents, on a range of cultured trabecular meshwork cell lines.', 'Migration was assessed in 48-well modified Boyden chambers. The potential migratory stimulants were soluble fibronectin and glaucomatous and nonglaucomatous aqueous humor. The glaucomatous aqueous samples were collected from patients undergoing trabeculotomy for primary open-angle glaucoma and the normal aqueous from normal bovine eyes and patients undergoing cataract surgery. The target cell types were normal human and bovine meshwork cells grown from explants and two human transformed meshwork cell lines from a normal (HTM-5) and a glaucomatous (HTM-3) source.', 'Soluble fibronectin stimulated all the target cells to migrate with an optimal concentration ranging from 1 to 30 microg/ml, and Zigmond Hirsch checkerboard analysis indicated that both chemotaxis and chemokinesis took place. All the aqueous humor samples stimulated migration of the meshwork cell lines at an optimal concentration of 200 microl/ml. Glaucomatous aqueous humor stimulated a greater migratory response than nonglaucomatous aqueous for two of the four target cell types (P < or = 0.03). Neutralization of the fibronectin content of nonglaucomatous and glaucomatous aqueous by addition of excess anti-fibronectin antibody indicated that fibronectin could account for 35% to 80% of the migratory activity of the aqueous.",
            "output": [
                "Does aqueous humor stimulate the migration of human trabecular meshwork cells in vitro?"
            ]
        },
        {
            "id": "task847-3eea506f36ad478da20d5ec08f944d43",
            "input": "Increased concentrations of metalloproteinases are associated with the invasive and metastatic behavior of several human malignant tumors. Normally, enzymatic activity is tightly regulated by nonspecific mechanisms and specific inhibitors. The aim of the study was to determine the potential of a synthetic metalloproteinase inhibitor, batimastat, to show its in vitro effect on MatLyLu cancer cells and its in vivo effect on tumor growth in orthotopic cancer (R3327 Dunning tumor) in rats.', 'In vitro, a dose response curve of batimastat was generated over 4 days using the MTT assay. Prostate cancer was injected in vivo in male Copenhagen rats by inoculating R3327 Dunning tumor cells (MatLyLu) into the ventral prostatic lobe of 30 rats. Each of 10 rats received batimastat (30 mg/kg body weight) or vehicle administered once a day by i.p. application beginning the day of cell inoculation. Ten rats remained untreated. The effect on local tumor growth was evaluated by measuring tumor weights 20 days after tumor cell inoculation.', 'Significant inhibition of tumor cell proliferation in vitro occurred at 400 and 4,000 ng/ml batimastat. After orthotopic cell inoculation, tumors grew to mean weights of 18.9 g in the control group without treatment, to 22.3 g in the vehicle group, and to 11.1 g in the treated group. In comparison to the control group and to the vehicle group, tumor weights increased significantly less under treatment with batimastat.",
            "output": [
                "Does synthetic inhibitor of matrix metalloproteinases ( batimastat ) reduce prostate cancer growth in an orthotopic rat model?"
            ]
        },
        {
            "id": "task847-e124e3033e2248b39d44841219acf63a",
            "input": "Ornithine decarboxylase (ODC) is the first key enzyme in the polyamine biosynthesis pathway. Polyamine is believed to participate in cellular proliferation and differentiation. To study the relationship between ODC and the pathogenesis of benign prostatic hyperplasia (BPH), the polyamine levels, ODC activities, and expression of ODC mRNA in benign hyperplastic and normal human prostates were assayed.', 'Polyamine contents and ODC activities in tissue extracts were determined by reverse-phase high-performance liquid chromatography and spectrophotometric procedures, respectively. The ODC mRNA levels were assayed by Northern blot analysis.', 'The contents of putrescine, spermidine, and spermine in BPH tissues were 2.2, 3.4, and 6.0 times higher than those in normal tissues, respectively; the ODC activity of BPH tissue was about 3.2 times higher than in normal tissue; the expression level of ODC mRNA in the BPH tissues was greater than that of normal tissues.",
            "output": [
                "Are ornithine decarboxylase activity and its gene expression increased in benign hyperplastic prostate?"
            ]
        },
        {
            "id": "task847-f46249288903468680b5d6488ee95b21",
            "input": "To use functional MRI (fMRI) to determine which brain regions are implicated when normal volunteers judge whether pretransected horizontal lines are correctly bisected (the Landmark test).', 'Manual line bisection and a variant thereof involving perceptual judgments of pretransected lines (the Landmark test) are widely used to assess unilateral visuospatial neglect in patients with neurologic disease. Although unilateral (left) neglect most often results from lesions to right temporoparietal cortex, the normal functional anatomy of the Landmark test has not been convincingly demonstrated.', 'fMRI was carried out in 12 healthy right-handed male volunteers who judged whether horizontal lines were correctly prebisected. In the control task, subjects detected whether the horizontal lines contained a transection mark irrespective of the position of that mark. Response was by two-choice key press: on half the trials, subjects used the right, and on half, the left hand. Statistical analysis of evoked blood oxygenation level-dependent responses, measured with echoplanar imaging, employed statistical parametric mapping.', 'Performing the Landmark task showed neural activity (p < 0.05, corrected) in the right superior posterior and right inferior parietal lobe, early visual processing areas bilaterally, the cerebellar vermis, and the left cerebellar hemisphere. Only the latter area showed a significant interaction with hand used.",
            "output": [
                "Do line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI?"
            ]
        },
        {
            "id": "task847-acb35989b17040d98346a4fadad0b84c",
            "input": "The safety and efficacy of prescribing a single maternal course of corticosteroid during pregnancy has been documented in human trials. However, the current trend is to prescribe repeated courses of corticosteroid. We investigated an aspect of the safety of this practice in an animal model.', 'Date-mated ewes received saline, single or four corticosteroid injections between days 104 and 124 of gestation (term = 150). Lambs were delivered on day 125 or 145 by caesarian section after spinal anaesthesia. Eye diameters were measured and semi-thin toluidine-blue-stained transverse sections of retinae were analysed using an Optimus Image Analysis program.', 'At 125 days, retinal measures in the ventral periphery and area centralis were significantly thinner than control (p = 0.0001). At 145 days, total eye size was significantly reduced compared with control (p = 0.03), and retinal measures in the ventral periphery (p = 0.0001), but not the area centralis (p = 0.19), remained significantly different from control.",
            "output": [
                "Is retinal maturation delayed by repeated , but not single , maternal injections of betamethasone in sheep?"
            ]
        },
        {
            "id": "task847-a3f7c09eadb3476c96e757f8a6a1a936",
            "input": "To determine the botanical identity, cytotoxicity, and antibacterial property of the commonly used toothbrush sticks in Ethiopia.', 'Research laboratories of the departments of Biology and Chemistry, Addis Ababa University between December 1993 and May 1995.', 'The study was performed by purchasing the commonly used toothbrush sticks from street markets in various towns of Ethiopia. Voucher specimens were collected and their botanical identity was determined following floral keys. The toothbrush sticks were ground in a mill and soaked in absolute methanol for 24 hours and filtered. The filtrates were dried in a rotary evaporator and the crude extracts were stored at 4 degrees C. The crude methanol extracts were used to test their antibacterial activity by impregnating into filter paper discs and placing on test plates of Staphylococcus aureus and Bacillus cerues. Their lethality to brine shrimp (Artemia salina) was performed following standard procedures.', 'Twenty different species of plant used as toothbrush were collected and their botanical identity determined. Crude methanol extracts of only Agave sisalana, Birbira and Hypericum revolutum test concentrations up to 500 micrograms/ml showed weak toxicity to brine shrimp. All the extracts showed antibacterial activity against Staphylococcus aureus and Bacillus cereus by agar diffusion method.",
            "output": [
                "Does ethnomedical aspects of the commonly used toothbrush stick in Ethiopia?"
            ]
        },
        {
            "id": "task847-dd0d5859414443b8925819a8fcf86a86",
            "input": "Motor evoked potentials (MEPs) and inhibition of voluntary contraction to transcranial magnetic stimulation (TMS) of the motor cortex have longer latencies than normal in patients with incomplete spinal cord injury (iSCI) when assessed using surface EMG. This study now examines the modulation of single motor unit discharges to TMS with the aim of improving resolution of the excitatory and inhibitory responses seen previously in surface EMG recordings.', 'A group of five patients with iSCI (motor level C4-C7) was compared with a group of five healthy control subjects. Single motor unit discharges were recorded with concentric needle electrodes from the first dorsal interosseus muscle during weak voluntary contraction (2%-5% maximum). TMS was applied with a 9 cm circular stimulating coil centred over the vertex. Modulation of single motor unit discharges was assessed using peristimulus time histograms (PSTHs).', 'Mean (SEM) threshold (expressed as percentage of maximum stimulator output (%MSO)) for the excitatory peak (excitation) or inhibitory trough (inhibition) in the PSTHs was higher (p<0.05) in the patients (excitation = 47.1 (5.9) %MSO; inhibition = 44.3 (3.2) %MSO) than in controls (excitation=31.6 (1.2) %MSO; inhibition = 27.4 (1.0) %MSO). Mean latencies of excitation and inhibition were longer (p<0.05) in the patients (excitation=35 (1.8) ms; inhibition = 47.1 (1.8) ms) than in the controls (excitation = 21.1 (1.6) ms; inhibition = 27 (0.4) ms). Furthermore, the latency difference (inhibition-excitation) was longer (p<0.05) in the patients (10.4 (2.1) ms) than in the controls (6.2 (0.6) ms).",
            "output": [
                "Does modulation of single motor unit discharge using magnetic stimulation of the motor cortex in incomplete spinal cord injury?"
            ]
        },
        {
            "id": "task847-40cc8caadb694565b1cc95baa4188ba2",
            "input": "We study a resistive-heating blanket in a volunteer model of severe accidental hypothermia to evaluate differences in rates of rewarming, core temperature afterdrop, and body heat content and distribution during active and passive rewarming.', 'Eight volunteers participated in a crossover design on 2 days. The volunteers were anesthetized and cooled to 33 degrees C (91.4 degrees F); anesthesia was subsequently discontinued, and shivering was prevented with meperidine. On one randomly assigned day, the volunteers were rewarmed passively with reflective foil (passive insulation), whereas on the other they were covered with a carbon fiber-resistive heating blanket set to 42 degrees C (107.6 degrees F; active rewarming). Trunk and head temperature and heat content were calculated from core (tympanic membrane) temperature. Peripheral (arm and leg) tissue temperature and heat content were estimated by using fourth-order regressions and integration over volume from 30 tissue and skin temperatures.', 'Core heat content increased 73+/-14 kcal (mean+/-SD) during 3 hours of active warming, but only 31+/-24 kcal with passive insulation, a difference of 41+/-20 kcal (95% confidence interval [CI] 27 to 55 kcal; P <. 001). Peripheral tissue heat content increased linearly by 111+/-16 kcal during active warming but only by 38+/-31 kcal during passive warming, a difference of 74+/-34 kcal (95% CI 50 to 97; P <.001). Consequently, total body heat increased 183+/-22 kcal during active warming but only 68+/-54 kcal with passive insulation, a difference of 115+/-42 kcal (95% CI 86 to 144 kcal; P <.001). Core temperature increased from 32.9 degrees C+/-0.2 degrees C to 35.2 degrees C+/-0. 4 degrees C during 3 hours of active warming, a difference of 2.3 degrees C+/-0.4 degrees C. In contrast, core temperature with foil insulation only increased from 32.9 degrees C+/-0.2 degrees C to 33. 8 degrees C+/-0.5 degrees C, a difference of only 0.8 degrees C+/-0. 4 degrees C. The difference in the core temperature increase between the two treatments was thus 1.5 degrees C+/-0.4 degrees C (95% CI 1. 2 degrees C to 1.7 degrees C; P <.001 between treatments). Active warming was not associated with an afterdrop, whereas the afterdrop was 0.2 degrees C+/-0.2 degrees C and lasted a median of 45 minutes (interquartile range, 41 to 64 minutes) with passive insulation.",
            "output": [
                "Is resistive heating more effective than metallic-foil insulation in an experimental model of accidental hypothermia : A randomized controlled trial?"
            ]
        },
        {
            "id": "task847-0569f9c591254193bf5cee27bce01f04",
            "input": "To clarify the social issues and problems associated with burn care in Japan, based on a cost analysis of acute burn care.', 'A retrospective review was undertaken of 71 patients admitted with burns at Nippon Medical School between January 1 and December 31, 1997. A cost analysis was performed for three major burn patients with a burn surface area (BSA) of 70% to 80% and three minor burn patients with a BSA of 20% to 30%. A questionnaire was administered to both burn patients and medical providers in all 127 emergency centers to help improve long-term quality of life (QOL).', '80% of burn patients were under age 70. In the major burn cases, the amount of reimbursement according to the government-regulated fee schedule was much less than the cost of treatment. The ratio of the cost of both medication and materials to total cost of treatment was higher for patients with major burns. Patients responding to the survey acknowledged being generally happy despite suffering from psychological and financial problems. A total of 413 medical providers from 63 institutions responded to the survey regarding improving long-term QOL.",
            "output": [
                "Do the cost of burn care and implications for efficient care?"
            ]
        },
        {
            "id": "task847-00a1fd46ef4b408a8af28dbac9f58fd6",
            "input": "The effects of exercise training on LV remodelling following large anterior myocardial infarction (MI) remains controversial. Blockade of the renin-angiotensin system has been shown to prevent ventricular dilation and deleterious remodeling. We therefore tested, in a rat model of chronic MI, whether any potentially deleterious effects of exercise on post-MI remodelling could be ameliorated by angiotensin II receptor blockade.', 'Male Wistar rats underwent coronary ligation or sham operation. Treatment with losartan (10 mg/kg/day) began 1 week post-MI and moderate treadmill exercise (25 m/min, 60 min/day, 5 days/week) was initiated 2 weeks post-MI. Systolic and diastolic pressure-volume relationships were measured in isolated, red-cell perfused, isovolumically beating hearts 8 weeks post-MI. Morphometric measurements were performed in trichrome stained cross sections of the heart. Five groups of animals were compared: sham (n=13), control MI (MI; n=11), MI plus losartan (MI-Los; n=13), MI plus exercise (MI-Ex; n=10) and MI plus exercise and losartan (MI-Ex-Los; n=12).', 'Infarct size (% of left ventricle, LV) was similar among the infarcted groups [MI=43+/-4%, MI-Los=49+/-2%, MI-Ex=45+/-1%, MI-Ex-Los=48+/-2% (NS)]. Exercise, losartan and exercise+losartan treatments all attenuated LV dilation post-MI to a similar degree. Exercise training increased LV developed pressure in both untreated and losartan treated hearts (P<0.05 vs. other MI groups). In addition, exercise resulted in additional scar thinning in untreated hearts, while no additional scar thinning was seen in post-infarct hearts receiving both losartan and exercise.",
            "output": [
                "Does angiotensin II receptor blockade attenuate the deleterious effects of exercise training on post-MI ventricular remodelling in rats?"
            ]
        },
        {
            "id": "task847-d51bb6cd190640fbad3ad5051efd1a76",
            "input": "The human heart expresses type 2 angiotensin (AT(2)) receptor, but the function is poorly defined.', 'In the present study, we investigated (1) the cellular localization of the AT(2) receptor and (2) the relationship between the AT(2) receptor protein expression and the cardiac function of patients with ischemic heart disease. The receptor localization was assessed by immunohistochemistry and the protein expression was quantified by Western blotting in atrial tissues freshly obtained from 22 patients undergoing coronary artery bypass graft surgery (63.0+/-11.0 years old; male ratio, 85%). Prior to the surgery, blood was drawn for determination of atrial-natriuretic hormone level and the left ventricular function was assessed by ultrasound cardiography.', 'The results of immunohistochemistry showed that the AT(2) receptor was localized to cardiomyocytes and was not present in fibroblasts, vascular smooth muscles, or vascular endothelium. Atrial tissues showed various degrees of structural remodeling, but the localization of the AT(2) receptor was not altered in any tissue sections. The amount of the AT(2) receptor was negatively correlated with end-diastolic left ventricular diastolic dimension (r=-0.56, P<0.01), calculated left ventricular mass index (r=-0.51, P<0.02) and the plasma atrial natriuretic peptide (ANP) concentration (r=-0. 62, P<0.01) and positively correlated with left ventricular ejection fraction (r=0.48, P<0.05).",
            "output": [
                "Is type 2 angiotensin II receptor downregulated in cardiomyocytes of patients with heart failure?"
            ]
        },
        {
            "id": "task847-385c302af64349a0bba14b816426b5d0",
            "input": "Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues.', 'Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18 degrees C, and had their circulation arrested (60 minutes) and reperfused at 37 degrees C for 90 minutes (DHCA, n = 8); or (2) time-matched normothermic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside.', 'In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (110% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were impaired in DHCA (109% +/- 3%, p < 0.05) relative to CPB (137% +/- 6%). In renal arteries, endothelial (ACh) responses were impaired in DHCA (71% +/- 13%) relative to CPB (129% +/- 14%). Apoptosis (DNA laddering) occurred primarily in duodenal tissue, with a greater frequency in DHCA (56%, p < 0.05) compared with normothermic CPB (17%) and nonbypass controls (0%).",
            "output": [
                "Does hypothermic circulatory arrest cause multisystem vascular endothelial dysfunction and apoptosis?"
            ]
        },
        {
            "id": "task847-607b3489743f4951b7e3e49415965da2",
            "input": "To examine whether adrenomedullin, a novel vasoactive peptide produced by the placenta, participates in the uteroplacental hemodynamic alterations in intrauterine growth restriction, we studied the correlation between adrenomedullin levels and fetoplacental blood flow.', 'Maternal and umbilical blood samples were collected in pregnancies complicated by intrauterine growth restriction with abnormal umbilical artery Doppler findings and in control pregnancies. Adrenomedullin levels were measured by means of a specific radioimmunoassay, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries.', 'Mean adrenomedullin values in umbilical plasma were higher (P <.05) in patients with intrauterine growth restriction (63.7 +/- 34.2 pg/mL; n = 16) than in control subjects (38.1 +/- 14.8 pg/mL; n = 16). A significant correlation was found between maternal adrenomedullin levels and umbilical artery pulsatility index. Moreover, fetal adrenomedullin concentrations correlated negatively with middle cerebral artery pulsatility index and positively with umbilical artery pulsatility index/middle cerebral artery pulsatility index ratio.",
            "output": [
                "Is adrenomedullin increased in the fetoplacental circulation in intrauterine growth restriction with abnormal umbilical artery waveforms?"
            ]
        },
        {
            "id": "task847-24945b69b93b4ba4a057cd728047247e",
            "input": "Early detection of pathophysiological factors associated with permanent and severe brain damage in preterm infants requiring intensive care is a major issue in neonatal neurology. The aim of this study was to investigate if an abnormal CO2 reactivity of cerebral blood flow in high risk very low birth weight infants is associated with severe brain injury demonstrated at autopsy or by neurodevelopment examination at 18 months.', 'The CO2 reactivity of cerebral blood flow (xenon-133) was measured in 18 mechanically ventilated, severely ill, very low birthweight infants (gestational age 26-32 weeks, birthweight: 630-1360 g) during the first 36 hours of life. Cerebral outcome was assessed on autopsy findings (n = 8) or at the age of 18 months using Bayley developmental scales (n = 10).', 'Eight infants with normal development at 18 months (within mean +/- 2.5 SD of reference group) and two infants with normal cerebral autopsy findings had a median CO2 reactivity of 24.4%/kPa CO2 (interquartile range 14.7-41.2). Two infants with abnormal development (> 2.5 SD below mean) and six infants with hypoxic-ischaemic encephalopathy at autopsy has a median CO2 reactivity of 3.4%/kPa CO2 (interquartile range 8.0-11.7).",
            "output": [
                "Is loss of CO2 reactivity of cerebral blood flow associated with severe brain damage in mechanically ventilated very low birth weight infants?"
            ]
        },
        {
            "id": "task847-c384cbbe01054600873ceb724089bab8",
            "input": "It has been suggested that early localization of both necrosis and extrapancreatic fluid collections by contrast-enhanced computed tomography (CT) can predict the outcome in severe acute pancreatitis. These two assumptions were evaluated.', 'This study comprises 228 patients with a first attack of acute pancreatitis admitted to our clinic from 1987 to 1995 and for whom the prognostic value of a contrast-enhanced CT obtained within 72 h of admission was prospectively evaluated. These CTs were retrospectively re-evaluated for the localization of pancreatic necrosis and extrapancreatic fluid collections. The indication for dialysis and artificial ventilation, the development of pancreatic pseudocysts, the necessity for surgery (necrosectomy), and mortality were used as clinical parameters.', 'There was a significant correlation between the presence of pancreatic necrosis and extrapancreatic fluid collections versus the clinical parameters. The localization of pancreatic necrosis was of no importance for the outcome of the disease, whereas the increasing amount of extrapancreatic fluid collections paralleled the severity of acute pancreatitis.",
            "output": [
                "Are presence and extent of extrapancreatic fluid collections indicators of severe acute pancreatitis?"
            ]
        },
        {
            "id": "task847-5aa3ca481cc44abc95a7bf66c69806ba",
            "input": "Papillomavirus is the etiologic agent associated with cervical carcinoma. The papilloma E2 protein is able to regulate negatively the expression of E6 and E7 papilloma oncoproteins. Therefore, a new, highly attenuated vaccinia virus known as modified vaccinia virus Ankara (MVA), which carries the papillomavirus E2 gene, was used for the treatment of tumors associated with human papillomavirus.', 'Analysis of expression of the E2 gene from the recombinant vaccinia virus was performed by reverse transcription-polymerase chain reaction of RNA isolated from infected cells. Detection of the E2 protein was done by immunoprecipitation from proteins labeled with [(35)S]-methionine, isolated from infected cells. The therapeutic effect of the MVA E2 recombinant virus over human tumors was tested in nude mice bearing tumors generated by inoculation of HeLa cells. Series of 10 nude mice with tumors of different sizes were injected with MVA, MVA E2, or phosphate-buffered saline. Tumor size was monitored every week to assess growth.', 'The MVA E2 recombinant virus efficiently expressed the E2 protein in BS-C-1 cells. This protein was able to repress, in vivo, the papillomavirus P105 promoter, which controls the expression of the E6 and E7 oncoproteins. In nude mice the MVA E2 virus reduced tumor growth very efficiently. In contrast, tumors continued to grow in mice treated with MVA or PBS. The life expectancy of MVA E2-treated mice was also increased three- to fourfold compared with that of animals that received MVA or PBS.",
            "output": [
                "Is human tumor growth inhibited by a vaccinia virus carrying the E2 gene of bovine papillomavirus?"
            ]
        },
        {
            "id": "task847-9ec4a554b9594110be91447b52e02bfa",
            "input": "To the authors' knowledge, there is no previous report of squamous papilloma of the urinary tract. It is uncertain whether there is a correlation between squamous papilloma, condyloma acuminatum, and verrucous carcinoma.\", 'The authors evaluated the clinical and pathologic features of squamous papilloma (5 of the bladder, 2 of the urethra), condyloma acuminatum (3 cases), and verrucous carcinoma (3 cases) of the urinary bladder and performed human papillomavirus (HPV) DNA in situ hybridization studies to determine whether HPV was a common feature shared by these lesions. In addition, DNA ploidy evaluation by image cytometry and p53 immunohistochemical staining were performed.', 'Squamous papilloma of the urinary tract occurred in elderly women and followed a benign clinical course with infrequent recurrence. All squamous papillomas were HPV DNA negative and DNA diploid with no or minimal p53 nuclear accumulation. Condyloma acuminata of the bladder contained HPV DNA, increased p53 protein expression, and aneuploid DNA content. All three cases of condyloma acuminata were associated with coexistent condylomata of the external genitalia, and two required pelvic exenteration for uncontrolled expansile growth. Verrucous carcinoma of the bladder occurred in elderly patients. All three cases of verrucous carcinoma were negative for HPV DNA and DNA aneuploid, and they exhibited consistent p53 expression.",
            "output": [
                "Is squamous papilloma of the urinary tract unrelated to condyloma acuminata?"
            ]
        },
        {
            "id": "task847-8d949f8771ff49689de6456b64f3b6f4",
            "input": "Plasma von Willebrand factor antigen (vWF:Ag) has been used as a marker of endothelial perturbation in a number of vascular disorders. In this study, vWF:Ag was determined as an attempt to evaluate the severity of endothelial cell dysfunction in primary pulmonary hypertension (PPH) and congenital heart disease-associated pulmonary hypertension (CHD-PH) comparatively and to determine its impact on short-term survival.', 'Clinical, hemodynamic, and biochemical data were obtained from 11 patients with PPH and 24 with CHD-PH. Patient groups were similar in terms of age and pulmonary artery pressure. vWF:Ag was measured by electroimmunodiffusion. Patients were followed up for 1 year and at that time, data collected at the beginning of the study were subjected to univariate and multivariate analyses. vWF:Ag was increased in patients (normal reference value 87% +/- 23% activity, mean +/- SD), with higher levels in the PPH group (231% +/- 89%) in comparison with the CHD-PH group (127% +/- 68%) (P <.001). Multivariate analysis showed that survival was influenced by the underlying cause of pulmonary hypertension and vWF:Ag levels but not by patient age, sex, or pulmonary artery pressure. Seven of 10 nonsurvivors but only 4 of 25 survivors had PPH (P =.007). vWF:Ag was 255% +/- 90% in the nonsurvivor group and 121% +/- 54% in the survivors (P <.001).",
            "output": [
                "Does endothelial cell dysfunction correlate differentially with survival in primary and secondary pulmonary hypertension?"
            ]
        },
        {
            "id": "task847-d0e8c32c89744a73a10832140576073c",
            "input": "It remains controversial whether the cure of H. pylori infection improves NUD symptoms.', 'To conduct a double-blind placebo-controlled single centre study with concealed allocation to investigate this question.', 'Ninety NUD patients with H. pylori infection were randomly assigned to either the treatment group (50 patients) or placebo group (40 patients). The treatment group received omeprazole, amoxycillin, clarithromycin and the placebo group received omeprazole and placebos for 7 days. Symptoms were assessed every week for up to 12 weeks after completion of medication by a symptom questionnaire. Alteration of histological parameters for gastritis was also evaluated.', 'The infection was cured in 41 out of 48 patients in the treatment group and none in the placebo group. There was no significant difference in the mean symptom scores at any assessment point up to 12 weeks between the treatment and placebo groups. Regarding histological parameters, activity and inflammation, not atrophy or intestinal metaplasia, were significantly improved in the treatment group.",
            "output": [
                "Does cure of Helicobacter pylori infection improve symptoms in non-ulcer dyspepsia patients-a double-blind placebo-controlled study?"
            ]
        },
        {
            "id": "task847-05f6ec1448274188be075e4aad4a34a1",
            "input": "Long QT syndrome is a congenital abnormality of cardiac repolarization causing syncope and sudden death from ventricular tachyarrhythmias known as torsades de pointes. This hereditary cardiac disorder often shows an increase of the value of the QT interval corrected for heart rate over 0.45 s in a 12-lead electrocardiogram.', 'To find and identify pertinent mutations occurring in French Canadians by extracting genomic DNA from blood samples and performing a combination of polymerase chain reaction (PCR), single-strand conformational polymorphism and DNA sequencing.', 'A novel mutation was identified in the S5 region of the HERG potassium channel. In codon 564 CTA, T was replaced by C, resulting in a leucine to proline substitution. Two family members had the mutation in two distinct generations. A new restriction site was created at this position and therefore enabled the development of a rapid diagnostic test using PCR. HERG wild type and mutant potassium channel mRNAs were then expressed in Xenopus laevis oocytes.",
            "output": [
                "Does the distinct HERG missense mutation L564P cause long QT syndrome in one French Canadian family?"
            ]
        },
        {
            "id": "task847-e35859f682d347809fc9b8e1084a36b7",
            "input": "To determine whether prothrombin is present in follicular fluid and whether the enzymatic pathways for prothrombin activation are similar to those in plasma.', 'Follicular fluid samples collected at the time of oocyte harvest for an assisted reproductive technology procedure (ART) were analyzed for a panel of hemostatic proteins with use of a combination of functional, chromogenic, and Western ligand blot analysis.', 'An ART clinic and an academic research laboratory.', 'Women undergoing ART.', 'None.', 'Determination of components of thrombin generation and thrombin modulatory systems using functional and antigenic assay procedures.', 'Both prothrombin and components of the prothrombinase enzyme complex, which includes factors V, VII, and X, are present in follicular fluid. Other hemostatic proteins, including factors VIII and IX and vonWillebrand factor, are absent. The direct activation of prothrombin to thrombin is similar in follicular fluid and plasma. Like plasma, inhibitors of both thrombin and thrombin generation, including antithrombin, protein C, and alpha2-macroglobulin, are present in follicular fluid.",
            "output": [
                "Does human ovarian follicular fluid have functional systems for the generation and modulation of thrombin?"
            ]
        },
        {
            "id": "task847-c67061a4cd314bf092fc72c7ad22a5e7",
            "input": "One of the most restricting factors remaining in heart transplantation is the limited myocardial ischemia time. A new approach towards the prolongation of this time is the combination of primary cardioplegic arrest followed by continuous coronary oxygen persufflation (COP) with gaseous oxygen.', 'This technique was applied in pig hearts, which we transplanted orthotopically after cardioplegic arrest by original (n = 5) and modified (addition of hyaluronidase: n = 11) Bretschneider HTK solution and 14 h of hypothermic preservation. Depending on the different preservation techniques, we created four groups: (1), original HTK (HTK), n = 5; (2), modified HTK (mHTK), n = 5; (3), modified HTK solution plus COP (mHTK + COP), n = 6; and (4), as a control five hearts were transplanted after cardioplegic arrest by the original HTK solution and a cold ischemia time of 3 h comparable to clinical routine procedure.', 'After 14 h of preservation and orthotopic transplantation, cardiac functional recovery in mHTK + COP hearts was similar to control hearts, and improved compared to hearts of both other groups. Hemodynamics were significantly better in hearts preserved by mHTK + COP and in the control group compared to the HTK-hearts (P < 0.05), not significant compared to mHTK hearts (dp/dt(max) in % of preoperative +/- standard error of mean (SEM): mHTK + COP, 85 +/- 9; control, 85 +/- 10.5; mHTK, 59 +/- 14; HTK, 50 +/- 4). The cardiac output (CO) in % of preoperative was: mHTK + COP, 68 +/- 5.4; control, 64 +/- 4; mHTK, 44 +/- 2.7; HTK, 25 +/- 11. The ATP of left ventricular myocardium in mHTK + COP hearts at 14.7 +/- 1 micromol/g dry weight (DW) and in the control at 14.59 +/- 1.8 was higher compared to that in mHTK at 12.2 +/- 2.8 (P is non-significant (n.s.) versus mHTK + COP and control) and in HTK-hearts at 7.0 +/- 0.5 (P < 0.05 versus mHTK + COP and control). CK-MB in percent of CK showed no increase in either group.",
            "output": [
                "Does coronary oxygen persufflation combined with HTK cardioplegia prolong the preservation time in heart transplantation?"
            ]
        },
        {
            "id": "task847-dafafcf2176643f2bb4e35b3505f589b",
            "input": "Uterine infection occurs in as much as 20% of preterm labor and results in increased decidual cytokines. The objective of this study was to examine the effect of interleukin-1 (IL-1) and the cyclooxygenase-2 (COX-2) inhibitor, NS-398, on myometrial prostaglandin (PG) production and COX-2 expression.', 'Human uterine myocytes were stimulated with IL-1 (0-50 ng/mL) over 24 hr. PGE2, PGF2alpha, and 6-keto F1alpha were measured by enzyme-linked immunosorbent assay. Both COX-1 and COX-2 proteins and mRNA were measured by western and northern blot, respectively.', 'IL-1 increased PG production beginning at 6 hr, COX-2 protein increased beginning at 4 hr and continued to increase at 24 hr. COX-2 mRNA increased at 2 hr and peaked at 4 hr. NS-398 blocked PG production but had no effect on COX-2 protein or mRNA.",
            "output": [
                "Does interleukin-1 stimulate human uterine prostaglandin production through induction of cyclooxygenase-2 expression?"
            ]
        },
        {
            "id": "task847-e335031b56994ef18215b9b3f46cac49",
            "input": "Empyema remains a cause of morbidity and mortality. Thoracoscopy has proved its versatility in the management of pleural space disorders. The suitability of video-assisted thoracic surgery (VATS) for decortication in the management of the fibrotic stage of empyema is unclear.', 'VATS evacuation of empyema and decortication was performed on seventeen patients presenting with pleural space infections. A retrospective review was performed and constitutes the basis of this report.', 'VATS evacuation of empyema and decortication was successfully performed in 13 of 17 patients. Blood loss was 325 +/- 331 cc. Mean hospital stay was 18 +/- 10 days. Postoperative hospitalization was 11 +/- 7 days. Chest tubes remained in place for 7 +/- 3 days. There were no operative mortalities.",
            "output": [
                "Is video-assisted evacuation of empyema the preferred procedure for management of pleural space infections?"
            ]
        },
        {
            "id": "task847-6f0855a0cf8249ed894c7efef4224aad",
            "input": "Expression of CINCs was regulated differentially in lipopolysaccharide-stimulated rat macrophages. We examined whether the expression of CINCs in lipopolysaccharide-stimulated rat macrophages is similarly inhibited by anti-inflammatory drugs.', 'Rat peritoneal macrophages were stimulated by lipopolysaccharide in the presence of anti-inflammatory steroids (dexamethasone, prednisolone and hydrocortisone) or non-steroidal anti-inflammatory drugs (indomethacin and piroxicam). The production and mRNA expression of three types of CINCs were measured using enzyme-linked immunosorbent assay and northern hybridization.', 'Anti-inflammatory steroids; dexamethasone, prednisolone and hydrocortisone, dose-dependently inhibited the production of CINC-1, -2 and -3, whose inhibitory patterns were similar to each other. Furthermore mRNA expression of each CINC was inhibited by dexamethasone in a dose-dependent manner. In contrast, non-steroidal anti-inflammatory drugs, indomethacin and piroxicam were without effect. Expression of each CINC was regulated differently; the production of CINC-1 reached a maximum at 12 h and then slightly decreased after lipopolysaccharide stimulation, whereas that of CINC-2 and CINC-3 increased up to 24 h. Dexamethasone inhibited the CINCs production and mRNA expression at 9 h after lipopolysaccharide stimulation.",
            "output": [
                "Is the expression of three types of CINCs by lipopolysaccharide-stimulated rat macrophages inhibited similarly by anti-inflammatory steroids?"
            ]
        },
        {
            "id": "task847-966a80fe84a84809910266ce64c739a6",
            "input": "Lung injury after cardiopulmonary bypass is a serious complication for infants with congenital heart disease and pulmonary hypertension. Excessive neutrophil sequestration in the lung occurring after reestablishment of pulmonary circulation implies that interaction between neutrophils and pulmonary endothelium is the major cause of lung injury.', 'Thirty infants with either ventricular septal defect or atrioventricular septal defect and with pulmonary hypertension were enrolled in this study. We performed continuous pulmonary perfusion during total cardiopulmonary bypass on 16 patients (perfused group) and conventional cardiopulmonary bypass on 14 patients (control group). PaO2/FiO2 and neutrophil counts were assessed from immediately before surgery to 24 hours after termination of cardiopulmonary bypass.', 'PaO2/FiO2 was higher in the perfused group than in the control group, and the difference was significant throughout the study period. Neutrophil counts decreased below prebypass values in both groups at 30 minutes after aortic unclamping, and the difference was significant in the control group but was not in the perfused group. Duration of postoperative ventilatory support was significantly less in the perfused group.",
            "output": [
                "Does continuous pulmonary perfusion during cardiopulmonary bypass prevent lung injury in infants?"
            ]
        },
        {
            "id": "task847-e1f1d0ba0ca341c9a2dea528383ff782",
            "input": "Increased apoptosis has recently been reported in the heart of spontaneously hypertensive rats (SHRs).', 'To investigate the molecular basis of apoptosis in the left ventricle of SHRs in terms of the expression of Bcl-2 protein (which protects from apoptosis) and Bax protein (which acts as an apoptotic promoter). In addition, we analysed the involvement of alpha -adrenergic receptors in the left ventricular apoptosis of SHRs.', 'The study was performed in untreated SHRs (n=16) and SHRs that were orally treated with doxazosin (10 mg/kg body weight per day, for 15 days), a selective alpha1-receptor blocker (n=16). A group of Wistar-Kyoto (WKY) rats (n=16) was used as the control.', 'The left ventricles of untreated SHRs showed a significant increase in Bcl-2 protein expression and a reduced presence of Bax protein. The ratio of Bcl-2:Bax in SHRs was higher than in WKY rats, suggesting an anti-apoptotic state. Paradoxically, both the number of apoptotic cardiac cells and the cleavage of an 85-kDa fragment of the poly (ADP-ribose) polymerase (PARP), a marker of caspase-3 activity, were higher in the left ventricle of SHRs than in WKY rats, suggesting an apoptotic situation. Bax promotes cell apoptosis when it is bound to Bcl-2. We then determined the abundance of Bax-Bcl-2 complexes in the left ventricle of the two groups of animals. Bax-Bcl-2 complexes were more abundant in SHRs than WKY rats. In a second set of experiments, we analysed the role of alpha1-adrenergic blockade by doxazosin in the above-described mechanisms. Doxazosin treatment reduced the formation of Bax-Bcl-2 complexes in the left ventricle of SHRs, and this was accompanied by a decrease in the levels of 85kDa PARP and a reduction in apoptotic left ventricular cells.",
            "output": [
                "Does doxazosin modify Bcl-2 and Bax protein expression in the left ventricle of spontaneously hypertensive rats?"
            ]
        },
        {
            "id": "task847-a0b2417a506540769f90078593db3bbe",
            "input": "The mechanism by which stimulated neutrophils (polymorphonuclear leukocytes [PMNs]) damage pulmonary vascular endothelium was investigated.', 'The ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability was tested. Each series was conducted on 6 rats. To stimulate PMNs, they were agitated gently in a glass vial for 10 seconds.', 'Perfusing lungs with the stimulated PMNs elicited a fivefold increase in permeability compared with lungs perfused with the unstimulated cells. This increase in permeability was blocked completely by preincubation of stimulated PMNs with CD18 monoclonal antibody. This increase in permeability was also blocked completely by superoxide dismutase (SOD) or the xanthine oxidase (XO) inhibitor allopurinol. Pulmonary vascular hemodynamics were unaffected by any treatment protocol. The accumulation of stimulated PMNs within the lungs was not inhibited by SOD but was partially blocked by allopurinol.",
            "output": [
                "Does superoxide possibly produced in endothelial cells mediate the neutrophil-induced lung injury?"
            ]
        },
        {
            "id": "task847-d8106605796944e59533f9982855ad88",
            "input": "Gap junction channels provide for direct electrical coupling between cells, and play an important role in homeostasis and electrical coupling. One of the proteins that form gap junctions, Connexin40 (Cx40), shows restricted expression in the body, and is found in blood vessels and in the atrium and conduction system of the heart. We have investigated whether gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation.', 'A communication-deficient human hepatoma cell line (SKHep1) was stably transfected with human Cx40 cDNA and the properties of Cx40 gap junctions channels and their modulation by cAMP were analyzed using immunocytochemistry, Western blotting, dual patch clamp, and dye coupling.', 'Administration of 1 mM 8-Br-cAMP resulted in a mobility shift of Cx40 protein on western blot and increased macroscopic gap junctional conductance between cell pairs by 46.2 +/- 12.0% (mean +/- S.E.M., n = 8). Under control conditions, single channel experiments revealed three single channel conductances around 30, 80 and 120 pS. When cAMP was added, channel conductances of 46 and 120 pS were observed. In monolayers, cAMP also increased the permeability of Cx40 gap junction channels for Lucifer Yellow by 58%.",
            "output": [
                "Are human connexin40 gap junction channels modulated by cAMP?"
            ]
        },
        {
            "id": "task847-737c76aca01640acbd358e80b5703be2",
            "input": "The role of genistein in the effect of growth factors (KGF and EGF) on the growth of HPV 16 DNA-immortalized human cervical epithelial cells (HCE 16/3 cells) was studied.', 'Genistein affected the modulation effect of the growth factors on the growth of HCE 16/3 cells using [3H]-thymidine incorporation, immunocapture assay of uPA and tyrosine kinase assay.', 'The growth factors stimulated growth of HCE 16/3 cells in serum-free medium. However, genistein suppressed the growth stimulatory effect of growth factors on HCE 16/3 cells and also reduced KGF-enhanced uPA secretion in this cell line. The inhibitory effects might be associated with its attenuation of activity of tyrosine kinases of growth factors.",
            "output": [
                "Does [ Genistein suppress growth stimulatory effect of growth factors in HCE 16/3 cells ]?"
            ]
        },
        {
            "id": "task847-b9bf8041432d42569ea5f8866309b824",
            "input": "Intermittent pneumatic compression (IPC) has been shown, by duplex, to increase popliteal artery flow in normal legs and in legs with superficial femoral artery occlusion. The objective of this study was to see if IPC improves distal circulation in legs with severe infra-popliteal disease.', 'Sixteen chronically ischemic legs with arteriographically demonstrated crural or pedal disease were studied during compression with an ArtAssist compression-device. This device delivers rapid compression of the foot and calf. Cutaneous laser-Doppler flux was measured continuously at the dorsal aspect of the distal forefoot. The findings were compared to those in thirteen normal controls of similar age.', 'In ischemic legs, the spontaneous changes in skin-flux are minimal: mean resting flux in sitting position was 0.87 +/- 0.46 AU (Arbitrary Units). Upon activation of the compression device the maximum flux increased to 4.55 +/- 1.35 AU. The difference was statistically significant (p < 0.001). This response was similar to that in normal controls.",
            "output": [
                "Does rapid intermittent compression increase skin circulation in chronically ischemic legs with infra-popliteal arterial obstruction?"
            ]
        },
        {
            "id": "task847-9a5a3a2dcb65487d9d74e86ed564f599",
            "input": "To determine whether insulin resistance (IR calculated using the HOMA model) has a dominant role in the clustering of cardiovascular risk factors in the Asian Indian population.', 'A total of 654 non-diabetic subjects aged > or =40 years (male 396: female 258) were selected from a population survey. They had estimates of fasting and 2 h plasma glucose, insulin levels, body mass index (BMI), waist-to-hip ratio (WHR) and blood pressure. Factor analysis was carried out using the principle components analysis (PCA) with varimax orthogonal rotation of continuously distributed variables, considered to represent the components of insulin resistance syndrome including the calculated IR.', 'There were three major clusters of cardiovascular disease (CVD) risk variables in men and four clusters in women. Insulin resistance, 2 h plasma glucose, insulin and obesity aggregated as the major domain. Insulin resistance was not linked with hypertension. BMI was a common link for all the three factors in men, and for three of the four in women.",
            "output": [
                "Does insulin resistance alone explain the clustering of cardiovascular risk factors in southern India?"
            ]
        },
        {
            "id": "task847-667444a047d046bc838f53260299466f",
            "input": "We report on the early and intermediate-term follow-up results of self-expanding Wallstent (Schneider, Switzerland) implanted in children with congenital heart disease.', 'The inherent shortcomings of balloon-expandable stents prompted the trial of an alternative stent.', 'Twenty patients underwent 22 implantations of 25 self-expanding Wallstents between December 1993 and June 1997 in two institutions. The mean age and weight were 10.8+/-4.5 years and 30.5+/-14.2 kg, respectively. The patients were divided into two groups: 1) Group I comprised 17 patients with pulmonary arterial stenoses, 2) Group II comprised four patients with venous stenoses (one belonged to both groups). Sixteen patients underwent recatheterization at a median of 5.8 months (range 0.5 to 31, mean 8.1 months) after stenting. Hemodynamic and angiographic changes after the interventional procedures and complications were documented.', 'All the stents were successfully deployed in the intended position. In Group I, the narrowest diameter of the stented vessel increased from 4.1+/-1.5 to 8+/-2 mm (95% increase, p < 0.0001) while the systolic pressure gradient across decreased from 24.6+/-15.8 to 12.1+/-11.4 mm Hg (51% decrease, p = 0.001). In Group II, the dimensional changes of the narrowest segment increased from 4.3+/-0.5 to 7.5+/-0.4 mm (75% increase, p = 0.003), and the pressure gradient reduced from 5.0+/-2.9 to 0.9+/-1.0 mm Hg (82% decrease, p = 0.04) across the stented venous channel. Distal migration of two optimally positioned stents occurred within 24 h of implantation. At recatheterization, significant neointimal ingrowth (>30% of the expanded diameter) was noted in 7 (28%) of the 25 implanted stents. This responded poorly to balloon dilation. Predisposing factors for the neointimal ingrowth included stents of smaller diameter (<9 mm) and longer period after implantation.",
            "output": [
                "Do early and intermediate-term complications of self-expanding stents limit its potential application in children with congenital heart disease?"
            ]
        },
        {
            "id": "task847-3e8ac06ec7594569a6cc6f44dbd2e520",
            "input": "This study was designed to examine whether or not adenovirus-mediated gene transfer of C-type natriuretic peptide (CNP) can prevent coronary restenotic changes after balloon injury in pigs in vivo.', 'Gene therapy to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) might be useful but requires a method applicable for in vivo gene delivery into the coronary artery as well as the efficient vector encoding a potent antiproliferative substance. We tested whether the adenovirus-mediated gene transfer of CNP by use of an infiltrator angioplasty balloon catheter (IABC) might prevent the coronary restenotic changes after balloon injury.', \"Balloon angioplasty was performed in the left anterior descending and the left circumflex coronary artery in pigs. Immediately after the balloon injury, adenovirus solution encoding either CNP (AdCACNP) or beta-galactosidase (AdCALacZ) gene was injected with IABC into the balloon-injured coronary segments. Expression of CNP was assessed by immunohistochemical staining and cyclic guanosine 3',5'-monophosphate (cGMP) measurement. Coronary restenotic changes were evaluated by both angiographic and histological examinations.\", 'CNP was highly expressed in the media and the adventitia of the coronary artery at the AdCACNP-transfected but not at the AdCALacZ-transfected segment. In the AdCALacZ-transfected segment, vascular cGMP levels tended to be reduced as compared with the untreated segment, whereas in the AdCACNP-transfected segment, vascular cGMP levels were restored. Angiographic coronary stenosis was significantly less at the AdCACNP-transfected than at the AdCALacZ-transfected segment. Histological examination revealed that this was achieved primarily by the marked inhibition of the geometric remodeling of the coronary artery by the CNP gene transfer.",
            "output": [
                "Does local adenovirus-mediated transfer of C-type natriuretic peptide suppress vascular remodeling in porcine coronary arteries in vivo?"
            ]
        },
        {
            "id": "task847-f71677e7b07848e389ae559cf72197e0",
            "input": "To test the hypothesis that neutrophil adhesion to expanded polytetrafluoroethylene (ePTFE) and Dacron triggers cell death.', 'Vascular prosthetic infections are intransigent clinical dilemmas associated with excessive rates of death and complications. Impaired neutrophil function has been implicated in the infection of implanted cardiovascular devices. ePTFE and Dacron are potent neutrophil stimuli able to elicit activation responses such as reactive oxygen species production independent of exogenous/soluble agonists. Reactive oxygen species that are released into the medium when neutrophils are challenged by soluble agonists are known to cause self-destruction. The authors therefore sought to examine whether neutrophil adhesion to prosthetic graft materials decreases neutrophil viability by means of reactive oxygen species production.', 'Neutrophils were adhered to surfaces for up to 6 hours. Cell viability was monitored with propidium iodide staining and lactate dehydrogenase release.', 'Within 6 hours of adhesion to ePTFE and Dacron, respectively, 59% +/- 11% and 44% +/- 5% (n = 7) of the neutrophils were stained by propidium iodide. Indistinguishable results were obtained with plasma-coated ePTFE and Dacron. In contrast, less than 2% of the neutrophils adherent to fibrinogen-, immunoglobin-, or fetal bovine serum-coated polystyrene surfaces for 6 hours were positive for propidium iodide. The increase in membrane permeability to propidium iodide was accompanied by a two- to threefold increase in lactate dehydrogenase release. Pretreatment of neutrophils with N-acetyl-L-cysteine, cytochalasin D, or cyclosporin A significantly reduced the number of propidium iodide-positive ePTFE and Dacron adherent neutrophils.",
            "output": [
                "Does neutrophil adhesion to vascular prosthetic surfaces trigger nonapoptotic cell death?"
            ]
        },
        {
            "id": "task847-0dfba72cb937495abd9f1b7521e48d06",
            "input": "A study of the relation between the development of mechanical allodynia and the reorganization of primary afferent terminals in the sensory lamina of the rat spinal cord dorsal horn after partial dorsal root ganglion injury in rats.', 'To investigate the pathologic mechanisms of mechanical allodynia after partial dorsal root ganglion injury.', 'After experimental peripheral nerve injury causing neuropathic pain, myelinated afferent fibers sprout into lamina II of the dorsal horn. This lamina is associated with nociceptive-specific neurons that generally are not stimulated by myelinated fiber input from mechanical receptors. These morphologic changes are suggested to have significance in the pathogenesis of chronic mechanical allodynia, although it is not known whether this kind of morphologic change occurs after dorsal root ganglion injury.', 'After partial dorsal root ganglion crush injury, the mechanical force causing footpad withdrawal was measured with von Frey hairs, and myelinated primary afferents were labeled with cholera toxin B subunit horseradish peroxidase, a selective myelinated fiber tracer that identifies transganglionic synapses.', 'After partial dorsal root ganglion injury, mechanical allodynia developed in the corresponding footpad within 3 days and persisted throughout the experimental period. At 2 and 4 weeks after the injury, B subunit horseradish peroxidase-positive fibers, presumably myelinated afferents, were observed to be sprouting into lamina II of the dorsal horn on the injured side, but not on the contralateral control side.",
            "output": [
                "Does injury to dorsal root ganglia alter innervation of spinal cord dorsal horn lamina involved in nociception?"
            ]
        },
        {
            "id": "task847-081aec9bcc0149f8bdd2add8a7a52898",
            "input": "Human and ovine fetuses demonstrate an enhanced rate of spontaneous and angiotensin II-stimulated swallowing. Angiotensin II and nitric oxide synthase have been localized to thirst centers in the brain. This study was performed to determine whether central nitric oxide contributes to the regulation of angiotensin II-induced fetal swallowing.', 'Six pregnant ewes with near-term singleton fetuses were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram and esophageal electromyogram electrodes. After a 2-hour control period, fetuses were administered serial lateral ventricle injections (1 mL) of angiotensin II (3.2 microg; time, 2 hours) and N omega-nitro-L -arginine methyl ester (3 mg; time, 3 hours) and a repeat angiotensin II injection (3.2 microg; time, 5 hours). All fetuses received an additional control study of lateral ventricle injections of artificial cerebrospinal fluid on a previous day.', 'Angiotensin II injection significantly increased mean +/- SEM fetal swallowing (0.9 +/- 0.1 to 2.7 +/- 0.4 swallows/min). N omega-nitro-L -arginine methyl ester significantly decreased fetal swallowing to below the basal rate (0.4 +/- 0.1 swallows/min), and swallowing did not increase with the second angiotensin II dose (in the presence of nitric oxide blockade).",
            "output": [
                "Does nitric oxide modulate angiotensin II-induced drinking behavior in the near-term ovine fetus?"
            ]
        },
        {
            "id": "task847-a14aa3c6a61c4574b17c19ea865c285b",
            "input": "The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC).', 'The expression of cyclin D1 and p53 was evaluated by means of immunohistochemical analysis in 32 HNSCC patients with clinically and radiologically negative lymph nodes in whom metastatic involvement was subsequently demonstrated at histologic examination (pN+). A group of 64 head and neck cancer patients with histologically negative laterocervical lymph nodes (pN0) was used as a control.', 'Cyclin D1 and p53 expression were observed respectively in 42 (43.7%) and 48 cases (50%). Cyclin D1 expression significantly correlated with tumor extension and advanced clinical stage (p =.002 and p =.001, respectively). At univariate regression analysis, cyclin D1 expression significantly correlated with the presence of occult lymph node metastases (p =. 0007), and it remained an independent predictor at multivariate regression analysis (p =.0059).",
            "output": [
                "Is cyclin D1 expression predictive of occult metastases in head and neck cancer patients with clinically negative cervical lymph nodes?"
            ]
        },
        {
            "id": "task847-c9451cd5421b443f96dab8a518ef25ad",
            "input": "Although ionizing radiation (IR) has been demonstrated to attenuate vessel wall restenosis and intimal hyperplasia (IH), dose-related mural injury and atrophy are possible deleterious side effects. We tested the hypothesis that a radiosensitizing strategy may improve IR-induced inhibition of in vivo vascular smooth muscle cells (VSMCs) without influencing apoptotic cell death.', 'In 28 New Zealand White rabbits, the right common carotid artery (CCA) was injured and subjected to low-flow conditions to promote IH. The CCA was transfected with an adenoviral vector incorporating the cytosine deaminase (CD) gene (1 x 10(9) PFU/ml). 5-Fluorocytosine (5-FC), a prodrug that is converted to the radiosensitizing agent 5-fluorouracil (5-FU) by CD, was thereafter administered intravenously. The CCA was exposed to 5 Gy IR at 24 h. Intimal/medial (I/M) area and thickness ratios were determined in the harvested CCAs at 14 days. VSMC proliferative and apoptotic indices were assessed with immunohistochemistry.', 'A 50% reduction in I/M area was found in rabbits treated with IR and IR + CD/5-FC (0.19 +/- 0.03 and 0.18 +/- 0.02) when compared with untreated controls (UC) (0.37 +/- 0.06) (P = 0.005). This finding was substantiated by attenuation of I/M thickness in the IR groups [0.47 +/- 0.13 (IR), 0.41 +/- 0.11 (IR + CD/5-FC), 0.61 +/- 0.17 (UC)] (P = 0.007). The number of proliferating VSMCs was notably smaller when IR was combined with CD/5-FC (4.17 +/- 1.16 vs 2.97 +/- 1.09 log transformed cells/mm(2), P < 0.07). Apoptosis was similar in all groups.",
            "output": [
                "Does gene therapy enhance the antiproliferative effect of radiation in intimal hyperplasia?"
            ]
        },
        {
            "id": "task847-eda2bbb748ae4df2a5a809ffda887ef2",
            "input": "The C57BL/6J-Min/+ (Min/+) mouse bears a germline mutation in Apc and is therefore a model for familial adenomatous polyposis and sporadic colorectal cancer. Min/+ intestinal mucosa exhibits a marked tendency for spontaneous adenoma formation. Curcumin is a phenolic antioxidant known for its antitumor and immune modulatory functions in vitro. Curcumin prevents adenoma formation in Min/+ mice, through a mechanism that may be related to its immunomodulatory properties.', 'To study the relationship between intestinal immunity and curcumin-induced antitumor response, we used immunohistochemistry to characterize the effect of curcumin treatment on resident intestinal immune effector cells in Min/+ mice.",
            "output": [
                "Is inhibition of intestinal tumors by curcumin associated with changes in the intestinal immune cell profile?"
            ]
        },
        {
            "id": "task847-0ecb53048cc54189a8be4b11a0b90095",
            "input": "Bacterial translocation through the gastrointestinal tract is the crucial step in the pathogenesis of intraabdominal infections. We assessed whether aggregation substance (AS), a bacterial adhesin and virulence factor of Enterococcus faecalis, promotes bacterial translocation and colonic mucosal invasion in an ex vivo experiment.', \"Colonic mucosa of male Wistar rats was placed in a modified Ussing system. The mucosal side of the chamber was filled with a suspension of E. faecalis OG1X:pAM721 (AS-positive) or E. faecalis OG1X (AS-negative). The serosal side was filled with sterile Dulbecco's modified Eagle's medium. For assessment of colonic mucosal invasion the mucosal side was incubated for 2.5 h with a suspension of AS-positive or AS-negative enterococci. After being washed, a solution of gentamicin and penicillin G in tissue culture medium was added on both sides in order to kill extracellular bacteria. Subsequently, the mucosa was removed from the system, washed, lysed with Triton X-100, and homogenized. Viable intramural bacteria were quantified by plating serial dilutions of the homogenate on Todd-Hewitt broth agar plates. To quantify bacterial translocation samples which were taken at various time points from the serosal side were plated on Todd-Hewitt broth agar plates and colony forming units (CFU) were determined.\", 'Invasion of the AS-positive E. faecalis strain OG1X:pAM721 into the colonic mucosa was significantly higher than invasion rates of the AS-negative strain OG1X (2.88 log(10) CFU/ml vs 1.73 log(10) CFU/ml; P = 0.02). However, none of the tested strains was found to translocate from the mucosal to the serosal side within the incubation time of 4 h.",
            "output": [
                "Does aggregation substance promote colonic mucosal invasion of Enterococcus faecalis in an ex vivo model?"
            ]
        },
        {
            "id": "task847-c4be04c52ed94eadbb37ddf8623e639c",
            "input": "While some studies have shown that physicians with healthy personal habits are especially likely to discuss prevention with their patients, to our knowledge no one has published information testing whether physician credibility and patient motivation to adopt healthier habits are enhanced by physician's disclosures of their own healthy behaviors.\", 'Two brief health education videos about improving diet and exercise were produced and shown to subjects (n1 = 66, n2 = 65) in an Emory University general medical clinic waiting room in Atlanta, Ga. In one video, the physician revealed an additional half minute of information about her personal healthy dietary and exercise practices and had a bike helmet and an apple visible on her desk (physician-disclosure video). In the other video, discussion of personal practices and the apple and bike helmet were not included (control video).', 'Viewers of the physician-disclosure video considered the physician to be generally healthier, some-what more believable, and more motivating than did viewers of the control video. They also rated this physician to be specifically more believable and motivating regarding exercise and diet (P < or = .001).",
            "output": [
                "Does physician disclosure of healthy personal behaviors improve credibility and ability to motivate?"
            ]
        },
        {
            "id": "task847-28e13051346b42c48cb7a1f277483f45",
            "input": "Little is known about the role of the CO2 pneumoperitoneum on tumor cells that spread from the portal system into the liver during laparoscopic surgery for gastrointestinal malignancies. Therefore, we designed a study to investigate the effect of CO2 pneumoperitoneum on cancer cells implanted in the portal vein in a rabbit model.', 'Immediately after intraportal inoculation of 2.5x10(5) cells of VX2 cancer, the rabbits received either CO2 pneumoperitoneum at a pressure of 10 mm Hg for 30 min (pneumoperitoneum group, n = 14) or laparotomy alone for 30 min (laparotomy group, n = 14).', 'The number (p<0.01) and area of cancer nodules (p = 0.045) on the liver surface on day 17 were greater in the pneumoperitoneum group than in the laparotomy group. The frequency of cancer nodules >3.0 mm in diameter was higher in the pneumoperitoneum group than in the laparotomy group (p<0.001).",
            "output": [
                "Does pneumoperitoneum with carbon dioxide enhance liver metastases of cancer cells implanted into the portal vein in rabbits?"
            ]
        },
        {
            "id": "task847-636ca7d63358415784a519bb1b41272d",
            "input": "Although diabetic patients often have gastrointestinal complications, the gastric mucosal function in diabetes has not been well documented.', 'To investigate the effect of fasting on the gastric mucosa in C57BL/KsJ-db +/+ db (db/db) mice, genetically non-insulin-dependent diabetic animals.', 'Blood glucose levels, gastric mucosal morphology, and the amount of gastric mucin were examined before and after 18 h of fasting with free access to water in db/db mice and their non-diabetic littermates (db/m).', 'Although 18 h of fasting reduced the blood glucose levels of both db/db and db/m mice, fasting decreased the amount of gastric adherent mucin and caused haemorrhagic gastric lesions only in db/db mice. After fasting, oral administration of ethanol induced much more severe gastric damage in db/db than in db/m mice. The above fasting-induced gastric damage such as haemorrhagic lesions, loss of the mucin, and the increased sensitivity to ethanol worsened as the duration of diabetes became longer. Glucose ingestion in drinking water during the fasting counteracted the fall in blood glucose and prevented the decrease in the amount of gastric mucin and the formation of gastric mucosal lesions in db/db mice.",
            "output": [
                "Does fasting induce impairment of gastric mucosal integrity in non-insulin-dependent diabetic ( db/db ) mice?"
            ]
        },
        {
            "id": "task847-4af9b3f56aa24cfc8fffc45507a9a5a7",
            "input": "Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. However, of the known proinflammatory cytokines, only elevated plasma levels of interleukin-6 have been linked to unstable angina. We sought to examine the plasma levels of other major proinflammatory cytokines in similar clinical settings and to determine the extent of the relationship between inflammation and unstable coronary syndromes by measuring the levels of various proinflammatory cytokines in patients with stable and unstable angina.', 'We measured plasma levels of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) in 97 patients: 67 with stable angina, 24 with unstable angina, and 15 healthy controls.', 'Mean levels of IL-1beta were significantly higher in patients with unstable angina as compared to patients with stable angina (p =.009). Levels of IL-6 were significantly higher than control patients for both stable angina and unstable angina patients (p =.031 and.006, respectively). No significant differences were found in the levels of TNF-alpha.",
            "output": [
                "Are circulating levels of IL-1beta , a prothrombotic cytokine , elevated in unstable angina versus stable angina?"
            ]
        },
        {
            "id": "task847-3a1c3db647f0451c9a5164fb2e98eb17",
            "input": "The induction of cellular immune responses to melanocyte-specific enzymes such as the tyrosinase family of proteins is the goal of various clinical studies for the immunotherapy of melanoma. Tyrosinase-related protein-2 (TRP2) is an attractive model antigen for preclinical studies in C57BL/6 mice because it is naturally expressed by the murine B16 melanoma and can be recognized by self-reactive cytolytic T lymphocytes (CTL). Here we describe efforts to develop genetic immunization with dendritic cells (DC) for the immunotherapy of melanoma in this clinically relevant system.', 'Recombinant adenoviruses encoding green fluorescent protein (Ad-EGFP) and murine TRP2 (Ad-mTRP2) were constructed using Cre-loxP-mediated recombination. DC were generated in vitro from precursors in bone marrow and transduced with Ad-EGFP or Ad-mTRP2. Mice were immunized by direct injection of adenovirus or by injection of Ad-transduced DC. Induction of tumor immunity was assessed by intravenous challenge with B16 melanoma cells and enumeration of experimentally induced lung metastases.', 'Flowcytometric analysis of DC transduced with Ad-EGFP demonstrated endogenous fluorescence due to cytoplasmatic expression of EGFP in 30-60% of cells. Ad-EGFP-transduced DC simultaneously displayed the DC-specific marker NLDC145 and high levels of MHC and costimulatory molecules on their cell surface. Transduction of DC with Ad-mTRP2 resulted in strong intracellular expression of TRP2 which could be readily detected by immunostaining. Importantly, immunization of mice with cultured Ad-mTRP2-transduced DC completely prevented the development of lung metastases following an intravenous challenge with B16 melanoma cells. This striking protective effect was observed with both the intravenous and the subcutaneous route of DC immunization. In vivo depletion of T-cell subsets suggested that the protective effect of an immunization with Ad-mTRP2-transduced DC involved both CD8+ and CD4+ T-cells.",
            "output": [
                "Does dendritic cell-based genetic immunization in mice with a recombinant adenovirus encoding murine TRP2 induce effective anti-melanoma immunity?"
            ]
        },
        {
            "id": "task847-87fccbbc50174d93a2a50780fc9a818d",
            "input": "The prognostic significance of pathological Q waves appearing in the acute phase of myocardial infarction has not been determined. We investigated whether new Q waves on the presenting electrocardiogram of patients with acute ST-segment elevation were independently associated with a worse outcome after a first myocardial infarction.', 'The presence or absence of new Q waves on the presenting electrocardiogram was assessed in 481 patients who presented within 4 h of symptom onset and were randomized to receive either captopril or placebo within 2 h of streptokinase therapy for myocardial infarction. Ventriculography was performed at 22+/-6 days and mortality status was obtained at a median follow-up of 5.6 years. New Q waves were associated with a lower ejection fraction (51+/-13% vs 61+/-12%, P<0.0001), a larger end-systolic volume index (37 ml vs 28 ml, P<0.001), and increased cardiac mortality at 30 days (7% vs 2%, P=0.01) and at follow-up (17% vs 7%, P=0.002). On multivariate analysis, age (P<0.01), new Q waves at presentation (P<0.01) and a history of angina (P=0.046) were independent predictors of cardiac mortality, whereas randomization to captopril and the time from symptom onset to streptokinase administration were not.",
            "output": [
                "Do new Q waves on the presenting electrocardiogram independently predict increased cardiac mortality following a first ST-elevation myocardial infarction?"
            ]
        },
        {
            "id": "task847-6554e8935a9d4ea2951f0a8191ed832f",
            "input": "Baseline data collected on each patient at randomisation in controlled clinical trials can be used to describe the population of patients, to assess comparability of treatment groups, to achieve balanced randomisation, to adjust treatment comparisons for prognostic factors, and to undertake subgroup analyses. We assessed the extent and quality of such practices in major clinical trial reports.', 'A sample of 50 consecutive clinical-trial reports was obtained from four major medical journals during July to September, 1997. We tabulated the detailed information on uses of baseline data by use of a standard form.', 'Most trials presented baseline comparability in a table. These tables were often unduly large, and about half the trials inappropriately used significance tests for baseline comparison. Methods of randomisation, including possible stratification, were often poorly described. There was little consistency over whether to use covariate adjustment and the criteria for selecting baseline factors for which to adjust were often unclear. Most trials emphasised the simple unadjusted results and covariate adjustment usually made negligible difference. Two-thirds of the reports presented subgroup findings, but mostly without appropriate statistical tests for interaction. Many reports put too much emphasis on subgroup analyses that commonly lacked statistical power.",
            "output": [
                "Does subgroup analysis and other ( mis ) used of baseline data in clinical trials?"
            ]
        },
        {
            "id": "task847-7c143681e9214d13baff44e642c4ef86",
            "input": "During the mating pheromone response in budding yeast, activation of a mitogen-activated protein kinase (MAP kinase) cascade results in well-characterized changes in cytoskeletal organization and gene expression. Spatial reorganization of genes within the nucleus has been documented during cell-type differentiation in mammalian cells, but no information was previously available on the morphology of the yeast nucleus during the major transcriptional reprogramming that accompanies zygote formation.', 'We find that in response to mating pheromone, budding yeast nuclei assume an unusual dumbbell shape, reflecting a spatial separation of chromosomal and nucleolar domains. Within the chromosomal domain, telomeric foci persist and maintain their associated complement of Sir proteins. The nucleolus, on the other hand, assumes a novel cup-shaped morphology and a position distal to the mating projection tip. Although microtubules are required for this orientation with respect to the projection tip, neither microtubules nor actin polymerization are necessary for the observed changes in nuclear shape. We find that activation of the pheromone-response MAP kinase pathway by ectopic expression of STE4 or STE11 leads to identical nuclear and nucleolar reorganization in the absence of pheromone. Mutation of downstream effector MAP kinases Fus3p and Kss1p, or of the transcriptional regulator Ste12p, blocks nuclear shape changes, whereas overexpression of Ste12p promotes dumbbell-shaped nuclei in the absence of pheromone.",
            "output": [
                "Does mAP kinase signaling induce nuclear reorganization in budding yeast?"
            ]
        },
        {
            "id": "task847-9d17f746381d40aebf3ddf56c38e54b5",
            "input": "In the fruit fly Drosophila, the Inscuteable protein localises to the apical cell cortex in neuroblasts and directs both the apical-basal orientation of the mitotic spindle and the basal localisation of the protein determinants Numb and Prospero during mitosis. Asymmetric localisation of Inscuteable is initiated during neuroblast delamination by direct binding to Bazooka, an apically localised protein that contains protein-interaction motifs known as PDZ domains. How apically localised Inscuteable directs asymmetric cell divisions is unclear.', 'A novel 70 kDa protein called Partner of Inscuteable (Pins) and a heterotrimeric G-protein alpha subunit were found to bind specifically to the functional domain of Inscuteable in vivo. The predicted sequence of Pins contained tetratrico-peptide repeats (TPRs) and motifs implicated in binding Galpha proteins. Pins colocalised with Inscuteable at the apical cell cortex in interphase and mitotic neuroblasts. Asymmetric localisation of Pins required both Inscuteable and Bazooka. In epithelial cells, which do not express inscuteable, Pins was not apically localised but could be recruited to the apical cortex by ectopic expression of Inscuteable. In pins mutants, these epithelial cells were not affected, but neuroblasts showed defects in the orientation of their mitotic spindle and the basal asymmetric localisation of Numb and Miranda during metaphase. Although localisation of Inscuteable in pins mutants was initiated correctly during neuroblast delamination, Inscuteable became homogeneously distributed in the cytoplasm during mitosis.",
            "output": [
                "Does a protein complex containing Inscuteable and the Galpha-binding protein Pins orient asymmetric cell divisions in Drosophila?"
            ]
        },
        {
            "id": "task847-0360c13697344782be09ec739ffc09e5",
            "input": "Pentobarbital (PB) is widely used as a short-term sedative and anticonvulsive drug with a side-effect of relaxing muscle tone. We investigated block of nicotinic acetylcholine receptor (nAChR) channel currents by PB using the patch-clamp technique in combination with an ultrafast system for solution exchange. As a preparation, recombinant rat adult-type nAChR channels transiently expressed in HEK293 cells were used. Appli-cation of 1 mM acetylcholine to small cells or outside-out patches showed a transient current with fast activation and desensitization kinetics. Adding PB to the acetylcholine-containing solution resulted in a decrease of the time constant of current decay and of the peak current amplitude starting at concentrations >0.01 mM PB. Preincubation of nAChR channels with PB led to a decrease of the peak current amplitude without alteration of activation and desensitization kinetics caused by competitive block of nAChR channels. In conclusion, similar to the effect of d-Tubocurarine, block of nAChR channel currents by PB can be explained by a combination of open-channel and competitive block.",
            "output": [
                "Does pentobarbital have curare-like effects on adult-type nicotinic acetylcholine receptor channel currents?"
            ]
        },
        {
            "id": "task847-6ac5abf9ddc8459f8aa0962bc9c6287f",
            "input": "Large concentrations of meperidine inhibit N-methyl-D-aspartate-(NMDA) receptor channels by channel block mechanisms. Extracellular pH regulates the activity and drug sensitivity of NMDA-receptor channels. We examined the influence of extracellular pH on sensitivity to meperidine of epsilon/zeta heteromeric NMDA-receptor channels expressed in Xenopus oocytes. Inhibition of epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 channels by meperidine was dependent on pH, with more inhibition at acidic pH and less inhibition at alkaline pH. The degree of voltage-dependence of meperidine block was only slightly affected by changes in pH, whereas affinity for meperidine was greatly reduced at alkaline pH. Furthermore, interaction of meperidine with Mg(2+) block was reduced at alkaline pH. Because the percentage of the protonated form of meperidine is only slightly affected by pH, changes in properties of the meperidine binding site may be involved in mechanisms of alteration of meperidine potency by pH.",
            "output": [
                "Is n-methyl-D-aspartate receptor channel block by meperidine dependent on extracellular pH?"
            ]
        },
        {
            "id": "task847-3cff59aa8c65404ca781523041c0de4c",
            "input": "Our laboratory has demonstrated that significantly more cell-mediated immunosuppression occurs after full laparotomy than after either anesthesia control or carbon dioxide (CO2) pneumoperitoneum. We further demonstrated that the postoperative immunosuppression is related to the length of the incision. Other investigators believe that the immunosuppression observed after laparotomy is caused by peritoneal exposure to small amounts of lipopolysaccharide found in circulating air. They believe that the better-preserved immune function associated with laparoscopic surgery results from the avoidance of air contamination of the peritoneal cavity. To investigate this hypothesis, we determined and compared postoperative lymphocyte proliferation rates after (a) laparotomy in room air, (b) laparotomy in a CO2 chamber, (c) CO2 insufflation in a murine model, and (d) anesthesia alone.', 'Female C3H/He mice (n = 21) were divided randomly into four groups: (a) anesthesia control, (b) air laparotomy, (c) CO2 laparotomy, and (d) CO2 insufflation. The control mice underwent no procedure. The group 2 animals underwent a full midline incision (xiphoid to pubis) and exposure to room air for 20 min and then were clipped closed. The group 3 mice underwent a full midline incision in a sealed CO2 chamber for 20 min, and the group 4 mice insufflation with CO2 gas at 4 to 6 mm Hg for 20 min. Splenocytes were harvested from all the animals on day 2 after the interventions. Lymphocyte proliferation then was assessed using the nonradioactive colorimetric MTS/PMS system 72 h after concanavalin-A stimulation.', 'There was no significant difference in lymphocyte proliferation between the air and CO2 laparotomy groups. Lymphocyte proliferation in the anesthesia control and CO2 insufflation groups was significantly higher than in both the air laparotomy (p<0.05) and CO2 laparotomy (p<0.05) groups (p values by Tukey-Kramer test). There was no significant difference between the anesthesia control and CO2 pneumoperitoneum groups.",
            "output": [
                "Is lymphocyte proliferation in mice after a full laparotomy the same whether performed in a sealed carbon dioxide chamber or in room air?"
            ]
        },
        {
            "id": "task847-b5fee85110804c1fa0c245e89038fcc4",
            "input": "Previous studies have suggested that post-irradiation GH insufficiency results from a loss of GHRH secretion, since many patients were able to release GH following exogenous GHRH stimulation. However, supramaximal doses of GHRH were used and the response may decline with time after radiotherapy. We re-evaluated the GHRH dose-response curve in patients post cranial irradiation and in controls.', 'Randomized controlled study.', 'Five adult male long-term survivors of childhood brain tumours (median age 21.8 years (18.4-26.7); 13.7 years (11.4-15.7) post-radiotherapy, >30Gy) and five matched controls were studied. An intravenous bolus of GHRH(1-29)NH(2) was administered in doses at the lower (0.05 microg/kg) and upper (0.15 microg/kg) range of the dose-response curves for young males, as well as the standard supramaximal dose (1. 0 microg/kg). GH was measured before stimulation, every 2min for the first hour and every 5min for the second hour. All studies were conducted in a random fashion.', 'Significantly lower peak and area under the curve (AUC) GH concentrations occurred in the irradiated group using 0.15 microg/kg (median peak Irradiated, 4. 5mU/l vs median Controls, 37.4mU/l; P<0.01) and 1.0 microg/kg (median peak Irradiated, 4.8mU/l vs median Controls, 15.2mU/l; P<0. 05) GHRH(1-29)NH(2). In irradiated subjects there was an incremental rise in GH output with increasing doses of GHRH(1-29)NH(2 )(median AUC: 122mU/l.min vs 179mU/l.min vs 268mU/l.min; P=0.007) reflecting altered pituitary sensitivity and reduced responsiveness.",
            "output": [
                "Is the GH response to low-dose bolus growth hormone-releasing hormone ( GHRH ( 1-29 ) NH2 ) attenuated in patients with longstanding post-irradiation GH insufficiency?"
            ]
        },
        {
            "id": "task847-b155a324172c431b834c17aaa3fa4000",
            "input": "Surgeon-performed ultrasonography is increasingly becoming part of the initial evaluation of patients after blunt or penetrating trauma. Currently, most institutions obtain a subxyphoid or subcostal view of the heart and pericardial space, and a three-view ultrasonogram of the abdomen to detect blood in the pericardial sac or in three dependent abdominal areas.', 'A left parastemal standard transverse transthoracic view is described in addition to the aforementioned views. This facilitates the visualization of the pericardial sac when a subxyphoid or subcostal view cannot be obtained because of anatomical reasons (narrow subxyphoid space) or local factors (pain, fractures, subcutaneous emphysema, or chest wall contusion).', 'The transthoracic view can be useful in patients where the subxyphoid view is difficult to obtain through the conventional approach. In most patients an excellent view of the pericardial sac and ventricles can be obtained and, therefore, expedites the diagnosis and treatment of patients with hemopericardium.",
            "output": [
                "Is transthoracic ultrasonography an alternative to subxyphoid ultrasonography for the diagnosis of hemopericardium in penetrating precordial trauma?"
            ]
        },
        {
            "id": "task847-252e8a142a834329bcb3fb6ad2b156ff",
            "input": "Because of the relatively poor results of frontal lobe epilepsy (FLE) surgery, identification of prognostic factors for surgical outcome is of great importance.', 'To identify predictive factors for FLE surgery, we analyzed the data of 61 patients (mean age at surgery 19.2) who had undergone presurgical evaluation and resective surgery in the frontal lobe. Postoperative follow-up ranged from 0.5 to 5 years (mean 1.78). Fifty-nine patients had MRI-detectable lesions. Histopathologic examination showed dysplasia (57.4%), tumor (16.4%), or other lesions (26.2%). Thirty postoperatively seizure-free patients were compared with 31 non-seizure-free patients with respect to clinical history, seizure semiology, EEG and neuroimaging data, resected area, and postoperative data including histopathology.', 'Three preoperative and two postoperative variables were related to poor outcome: generalized epileptiform discharges, generalized slowing, use of intracranial electrodes, incomplete resection detected by MRI, and postoperative epileptiform discharges. The only preoperative factor associated with seizure-free outcome was the absence of generalized EEG signs. Multivariate analysis showed that only the absence of generalized EEG signs predicts the outcome independently. Moreover, the occurrence of a somatosensory aura, secondarily generalized seizures, and negative MRI was identified as additional independent risk factors for poor surgical results.",
            "output": [
                "Does eEG predict surgical outcome in lesional frontal lobe epilepsy?"
            ]
        },
        {
            "id": "task847-cb45d86e09724a54993ec237f42db41d",
            "input": "The purpose of this study was to test whether basic fibroblast growth factor (bFGF) participates in arterialized vein graft remodeling.', 'Rabbits underwent in vivo gene transfer and carotid interposition vein grafting. Segments of external jugular vein were infected with an adenovirus that expressed antisense bFGF RNA (Ad.ASbFGF) at 1 x 10(10) PFU/mL to inhibit new synthesis of bFGF by cells in the vein graft wall. Control rabbits were treated with either adenovirus that encoded beta-galactosidase (Ad.lacZ) at 1 x 10(10) PFU/mL or vehicle (phosphate-buffered saline solution [PBS]). At 3 days, 3 grafts per treatment group were harvested for the determination of gene expression of ASbFGF RNA by reverse transcriptase-polymerase chain reaction. Rabbits were killed, and perfusion was fixed 2 months after the grafting. Total wall thickness and lumen circumference of vein grafts and normal arteries were measured in cross sections. Calculated mean tangential stress (+/-SD) for the ASbFGF-treated group and controls was compared for significance. Grafts were immunohistochemically stained to assess bFGF protein production.', 'Only the grafts infected with the Ad.ASbFGF gene expressed ASbFGF RNA. Grafts that were treated with Ad.ASbFGF displayed lower tangential stress (10.9 +/- 2.3 dynes/cm(2)) than PBS alone (22 +/- 2.8 dynes/cm(2)) or Ad. lacZ-treated controls (20.6 +/- 5.4 dynes/cm(2); P <.001). Tangential stress in the Ad.ASbFGF group was comparable to a normal carotid artery (13.9 +/- 2.1 dynes/cm(2)). The difference in mean total wall thickness was significant among the 3 treatment groups: Ad.ASbFGF, 164 +/- 3.4 microm); Ad.lacZ, 100 +/- 3.3 microm; and PBS, 96 +/- 3.6 microm; P <.01). Luminal circumference was not different among the groups. The Ad.ASbFGF-treated vein graft wall was composed of thick layers of concentric smooth muscle cells and elastin fibers in contrast to the sponge-like appearance observed in control arterialized vein grafts. Reduction in bFGF protein was noted only in the Ad.ASbFGF-treated group.",
            "output": [
                "Does adenoviral-mediated expression of antisense RNA to basic fibroblast growth factor reduce tangential stress in arterialized vein grafts?"
            ]
        },
        {
            "id": "task847-316b89fe874f4a95ad857b48fda9e885",
            "input": "Lung transplantation is a viable option for patients with cystic fibrosis. The current strategy of selection, based on spirometry and deterioration of quality of life, results in a high mortality on the waiting list. We reviewed the case histories of patients with cystic fibrosis accepted for lung transplantation to ascertain whether pulmonary hemodynamics could contribute to predict life expectancy.', 'Forty-five patients with cystic fibrosis were accepted: 11 died on the waiting list (group I), 24 underwent transplantation (group II), and 10 are still waiting (group III). During evaluation we recorded spirometry, oxygen requirement, ratio of arterial oxygen tension to inspired oxygen fraction (PaO (2)/FIO (2)), arterial carbon dioxide tension (PaCO (2)), 6-minute walk test results, right ventricular ejection fraction, echocardiography, and pulmonary hemodynamics. We compared data from group I, II, and III patients. A comparison was also made within group II between the data collected at the time of evaluation and at the time of transplantation to quantify the deterioration during the waiting time.', 'The waiting time, spirometry, 6-minute walk test results, and right ventricular ejection fraction did not differ among the three groups. A statistically significant difference was found for PaO (2)/FIO (2), PaCO (2), mean pulmonary artery pressure, cardiac index, pulmonary arterial wedge pressure, and intrapulmonary shunt between groups I and II. Groups I and III showed statistically significant differences for mean pulmonary artery pressure, PaO (2)/FIO (2), and systemic vascular resistance indexed. No differences were observed between groups II and III. The comparison within group II showed a significant deterioration of pulmonary hemodynamics during the waiting time.",
            "output": [
                "Do pulmonary hemodynamics contribute to indicate priority for lung transplantation in patients with cystic fibrosis?"
            ]
        },
        {
            "id": "task847-6b18ca262ace4bf89019a0ae380dc86d",
            "input": "Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate xenotransplantation.', 'The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation.', 'Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections.', 'Mean lung survival for the experimental group was increased when compared with controls, 240 +/- 0 minutes versus 35.3 +/- 14.5 minutes, respectively, with a P value of less than.01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 +/- 87 mm Hg. L(-1). min(-1), in contrast to the control group (1579 +/- 722 mm Hg. L(-1). min(-1); P <.01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 +/- 1.41 mL. cm(-2) H(2)O and 4.11 +/- 2.84 mL. cm(-2) H(2)O, respectively; P <.01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group.",
            "output": [
                "Are transgenic swine lungs expressing human CD59 protected from injury in a pig-to-human model of xenotransplantation?"
            ]
        },
        {
            "id": "task847-d7dbecfa3fd54c6182c854f72d57d7f8",
            "input": "To better understand B-cell activation in MS by analyzing the immunoglobulin (Ig)G heavy chain variable region (VH) repertoire found in MS brains and comparing it with brain VH sequences in individuals with subacute sclerosing panencephalitis (SSPE)--a chronic encephalitis produced by measles virus (MV)-and characterized by an antigen-driven oligoclonal IgG response to MV antigens.', 'The specificity of oligoclonal IgG in MS CSF and plaques, and their relevance to the pathogenesis of MS is unknown.', 'Nested PCR was used to amplify and sequence the rearranged IgG heavy-chain VH repertoire in plaques of three acute MS brains and in three SSPE brains. A representative population of VH sequences from each tissue was aligned to the known 51 functional VH germline segments. From this the authors determined the closest VH family germline segment, and the degree and location of somatic mutations for each unique IgG.', 'As expected for an antigen-driven response against MV antigens, most VH sequences from the SSPE brains were mutated extensively compared with their closest germline segments. Furthermore, SSPE VH sequences accumulated replacement mutations preferentially in the complementary-determining regions (CDRs) relative to framework regions-features normally observed during antigen-driven selection. A comparison of VH family and germline usage also demonstrated that each SSPE brain had its own unique IgG response. When the authors compared the VH response in MS plaques with SSPE, MS VH sequences were also mutated extensively, displayed a preferential accumulation of replacement mutations in CDRs, and were unique in each MS brain.",
            "output": [
                "Does comparison of immunoglobulin G heavy-chain sequences in MS and SSPE brains reveal an antigen-driven response?"
            ]
        },
        {
            "id": "task847-30ed454012c5485bb9f38653bb0a4adb",
            "input": "The purpose of this study was to investigate intracellular redistribution of muscarinic cholinergic receptor (m2AChR) and the roles of receptor phosphorylation and gene transcription as underlying mechanisms in the rat heart during different phases of sepsis.', 'Sepsis was induced by cecal ligation and puncture (CLP). The density of m2AChR in the sarcolemmal and light vesicle fractions was studied using [3H]-quinuclidinyl benzilate ([3H]-QNB). Phosphorylation of m2AChR was studied by labeling of the myocardial ATP pool by perfusing isolated hearts with [32P]H3PO4 followed by identification of the phosphorylated m2AChR with SDS-PAGE. The steady-state level of m2AChR mRNA was determined by RT-PCR and Southern blot analysis.', 'Septic rat hearts exhibit an initial hypercardiodynamic (9 h after CLP, early sepsis) and a subsequent hypocardiodynamic (18 h after CLP, late sepsis) state. During early sepsis, the Bmax for [3H]-QNB binding was increased in sarcolemma (+69%) but decreased in light vesicles (-22%), whereas during late sepsis, the Bmax was decreased in sarcolemma (-20%) but increased in light vesicles (+32%). The sum of Bmax for sarcolemmal and light vesicle fractions was increased during early sepsis (+43%) but decreased during late sepsis (-14%). The phosphorylation of m2AChR was decreased during early sepsis (-73%) but increased during late sepsis (+36% to +90%). The m2AChR mRNA abundance was increased during early sepsis (+52%) but decreased during late sepsis (-28%).",
            "output": [
                "Are biphasic redistribution of muscarinic receptor and the altered receptor phosphorylation and gene transcription underlying mechanisms in the rat heart during sepsis?"
            ]
        },
        {
            "id": "task847-4bf2bac44b2548ddb3abd0f92757ef77",
            "input": "The bradycardic agent zatebradine (UL-FS 49) reduces heart rate without negative inotropic or proarrhythmic effects. The aim was to experimentally characterize the influence of zatebradine on arterial baroreflex sensitivity (BRS) and heart rate variability (HRV) which are generally considered as estimates of vagal activity and have prognostic value in patients after myocardial infarction (MI).', 'Conscious rats were studied 3 days after left coronary artery ligation or sham-operation (SH). BRS was determined by linear regression analysis of RR-interval and mean arterial pressure changes evoked by intravenous (i.v.) injections of methoxamine and nitroprusside. HRV at rest was calculated from high-resolution electrocardiogram-recordings.', 'In MI-rats heart rate was similar to SH-rats, mean arterial pressure was lower and both BRS and HRV were markedly reduced. Zatebradine (0.5 mg/kg i.v.) reduced heart rate in MI-rats from 400 +/- 15 to 350 +/- 19 and in SH-rats from 390 +/- 19 to 324 +/- 6 beats/min without changing mean arterial pressure. Both BRS and HRV were restored in MI- and further increased in SH-rats by the drug. Effects of 0.05, 0.5 and 5 mg/kg zatebradine revealed a dose-dependency of heart rate reduction. The lowest dose enhanced reflex bradycardia despite little effect on heart rate and lack of effect on both reflex tachycardia and HRV.",
            "output": [
                "Does the bradycardic agent zatebradine enhance baroreflex sensitivity and heart rate variability in rats early after myocardial infarction?"
            ]
        },
        {
            "id": "task847-a42f5ace4af44be3be0acfd3fc82877b",
            "input": "Recent data indicate that oxidized low-density lipoprotein (ox-LDL) has several proatherogenic effects, e.g. induction of macrophage chemoattractants, adhesion molecules, cytokines, type-1 plasminogen activator inhibitor and platelet-derived growth factor A-chain by smooth muscle cells. Therefore, ox-LDL has been utilized as a marker of oxidative modification of proteins in atherosclerosis. Because heart valves consist of smooth muscle cells, fibroblasts and endothelial cells, and because valvular disease and coronary atherosclerosis could result from similar biological processes, we investigated ox-LDL accumulation in isolated aortic and pulmonary valves and coronary arteries from patients with angiographically proven coronary heart disease (CHD, n = 19), patients with idiopathic congestive heart failure (IDCM = idiopathic dilated cardiomyopathy, n = 20), and transplant donors.', 'Masson-Goldner staining and immunohistochemistry utilizing anti ox-LDL and CD68 were performed on paraffin sections of freshly isolated semilunar valves. Data were analyzed by digital image planimetry and by visual scoring of staining intensity.', 'Ox-LDL immunoreactivity was identified in the vascular aspect of the attachment line, in the deep valve stroma, and in the ventricular and vascular endothelium of the semilunar valves, colocalizing with macrophages. Valvular ox-LDL area was significantly increased in CHD-patients (P < 0.03) and IDCM-patients (P < 0.04) compared with controls. More ox-LDL was accumulating in the pulmonary valves than in the aortic valves (P = 0.04) as assessed by area and staining intensity. Valvular ox-LDL area in pulmonary valve and aortic valve was significantly correlated with ox-LDL accumulation in the intimal layer (P < 0.001) and medial layer (P < 0.001) of coronary arteries from the same patients.",
            "output": [
                "Does accumulation of oxidized LDL in human semilunar valves correlate with coronary atherosclerosis?"
            ]
        },
        {
            "id": "task847-25005ac80a294821b4c60efb38e32e1a",
            "input": "Angiostatin is a potent angiogenesis inhibitor that has been identified as a cryptic fragment of plasminogen molecule containing the first four kringle domain. Angiogenin, a 14-kDa monomeric protein, a potent blood vessel inducer, is expressed in tumors and present in mammalian plasma. The purpose of this study was to determine whether recombinant kringle 1-3 (rKI-3) of human plasminogen could interfere with angiogenesis induced by angiogenin and to evaluate the role of angiogenin in corneal angiogenesis in rabbit.', 'A Hydron polymer pellet containing 2.0 microg of angiogenin was implanted intrastromally into the superior cornea of each of 44 rabbit eyes. All eyes received an intrastromal pellet and were randomized into either one group treated with 12.5 microg of rKI-3 (n = 25) or the other group treated with phosphate-buffered saline (PBS; n = 19). Both pellets were positioned in parallel at the site 1.2 mm from the superior limbus. Two masked observers kept the angiogenesis score daily, based on the number and the length of new vessels. The corneas with induced angiogenesis also were examined histologically.', 'On the third day of the angiogenin pellets implantation, the eye treated with rKI-3 had less angiogenesis (mean score, 4.2 +/- 6.6) than eye treated with PBS (mean score, 16.1 +/- 17.1; p < 0.05, Mann-Whitney U test). The cornea treated with PBS also showed much more leukocyte adhesion than the cornea treated with rKI-3.",
            "output": [
                "Does recombinant kringle 1-3 of plasminogen inhibit rabbit corneal angiogenesis induced by angiogenin?"
            ]
        },
        {
            "id": "task847-225411eaa2ac47c3bda8f0860f48d461",
            "input": "To assess whether methylenetetrahydrofolate reductase(MTHFR) gene C677T polymorphism is associated with neural tube defects and preeclampsia.', 'Twenty- four mothers who had given birth to normal children, 27 mothers who had given birth to NTDs children, 120 normal women, and 57 women who had suffered from preeclampsia were genotyped for C677T polymorphism by using PCR/RFLP method.', '(1) VV genotype frequency in the normal mothers group it was 0.13, while in the NTDs mothers group it was 0.33; mothers with VV genotype were at 3 times increased risk to have a NTDs child, compared with the normal mothers. (2) In the normal women group VV genotype frequency was 0.15, while in the preeclampsia women group it was 0.31; women with VV genotype were at 2.5 times increased risk to have preeclampsia, compared with the normal women.",
            "output": [
                "Is [ The common C677T polymorphism in the methylenetetrahydrofolate reductase gene associated with neural tube defects and preeclampsia ]?"
            ]
        },
        {
            "id": "task847-045ea0eb7c194424a4ba57cddef83fb6",
            "input": "Thromboxane A2 (TXA2) activation is involved in several pathophysiological states in producing pulmonary hypertension. Local anesthetics (LA) inhibit signaling of TXA2 receptors expressed in cell models. Therefore, we hypothesized that LA may inhibit pulmonary vasoconstriction induced by the TXA2 analogue U 46619 in an isolated lung model.', 'Isolated rat lungs were perfused with physiological saline solution and autologous blood with or without the LA lidocaine, bupivacaine, ropivacaine, or the permanently charged lidocaine analogue QX 314 (all 1 microg/mL) as a pretreatment. Subsequently, pulmonary vasoconstriction was induced by 3 concentrations of U 46619 (25, 50, and 100 ng/mL) and the change in pulmonary artery pressure (Pa) was compared with each LA. In a second experiment, Pa responses to angiotensin II (0.1 microg), hypoxic pulmonary vasoconstriction (HPV, 3% O2 for 10 minutes), or phenylephrine (0.1 microg) were assessed to determine the specificity of ropivacaine effects on TXA2 receptors. Finally, reversibility of pulmonary vasoconstriction was determined by adding ropivacaine to the perfusate after pulmonary vasoconstriction was established with U 46619.', 'Ropivacaine, but not bupivacaine, lidocaine, or QX 314 significantly attenuated pulmonary vasoconstriction induced by 50 ng/mL U 46619 (35.9%, P<.003) or 100 ng/mL U 46619 (45.2%, P<.001). This effect of ropivacaine was likely to be specific for the thromboxane receptor because pulmonary vasoconstriction induced by angiotensin II, HPV, or phenylephrine was not altered. Ropivacaine did not reverse vasoconstriction when it was administered after U 46619.",
            "output": [
                "Does ropivacaine attenuate pulmonary vasoconstriction induced by thromboxane A2 analogue in the isolated perfused rat lung?"
            ]
        },
        {
            "id": "task847-80c3d52c4910415e8c516daa41a1046b",
            "input": "Polymorphonuclear leukocytes contain a large number of enzymes and bactericidal proteins stored in granules. Neutrophil activation induces degranulation and immediate release of these bioactive substances, including human neutrophil elastase (HNE) also known as elastase-2 (ELA2), which may contaminate whole blood units and blood components.', 'The HNE concentration was determined in the supernatants of blood components with a commercial enzyme-linked immunosorbent assay (ELISA). The effect of leukocyte depletion and storage was evaluated by testing whole blood, buffy-coat-reduced, and leukocyte-depleted red cell units. Buffy-coat-derived platelets and plasma were also tested.', 'HNE concentrations at day 1 were about 50 microg/l in all types of red cell components with the exception of leukocyte-depleted red cells (<0.26 microg/l). In leukocyte-depleted red cells, platelets and plasma, no significant increase was observed during storage. In whole-blood units and buffy-coat-reduced red cells, the HNE concentrations increased steadily and often exceeded 1,000 microg/l when the units expired.",
            "output": [
                "Does leukocyte depletion of red cell components prevent exposure of transfusion recipients to neutrophil elastase?"
            ]
        },
        {
            "id": "task847-33ad0061e8df4a5db557049bcf7f51c9",
            "input": "Allogeneic red blood cell transfusions may exert immunomodulatory effects in recipients including an increased rate of postoperative bacterial infection. It is controversial whether allogeneic transfusion is an independent predictor for the development of postoperative bacterial infection.', 'We analysed a prospectively collected database of 1,349 patients undergoing colorectal surgery in 11 centres across Canada. The primary outcome was the development of either a postoperative wound infection or intra-abdominal sepsis in transfused and nontransfused patients. The effect of allogeneic transfusion on postoperative infection was evaluated with adjustment for all the confounding factors in a multiple regression analysis.', 'The 282 patients who received a total of 832 allogeneic units had a significantly higher frequency of wound infections and intra-abdominal sepsis than the patients who were not transfused (25. 9 vs. 14.2%, p = 0.001). A significant dose-response relationship between transfusion and infection rate was demonstrated. Multiple regression analysis identified allogeneic transfusion as a statistically significant independent predictor for postoperative bacterial infection (OR 1.18, 95% CI 1.05-1.33, p = 0.007). Other independent predictors were anastomotic leak, repeat operation, patient age and preoperative haemoglobin level. The mortality rate was also significantly higher in the transfused group.",
            "output": [
                "Is allogeneic red blood cell transfusion an independent risk factor for the development of postoperative bacterial infection?"
            ]
        },
        {
            "id": "task847-4a2e918d3c6449e09f309d39869fef90",
            "input": "High concentrations of fibroblast growth factors (FGFs) are found in the heart. Even higher levels are measured during ischemia. Exogenous administration of FGF to ischemic myocardium promotes synthesis of collateral coronary circulation and induces local myocardial hypertrophy. The kinetics and the contribution of the heart and lungs to circulating basic FGF (bFGF) levels during cardiac surgery were characterized.', 'Plasma bFGF levels were measured in seven adults undergoing coronary artery bypass operations and 11 neonates undergoing congenital cardiac anomaly repair during cardiopulmonary bypass.', 'In both the adult and the neonatal groups, bFGF plasma levels increased significantly immediately after removal of the aortic cross-clamp (adult group 15.43+/-6.3 aorta cross-clamped versus 29+/-4.1 after release, P=0.011; neonatal group 17.09+/-9.43 aorta cross-clamped versus 43.55+/-14.25 after release, P=0.004) and declined thereafter. In the adult group, higher levels of bFGF were recorded in blood recovered from the coronary sinus than in the aortic root during aortic cross-clamping (63.14+/-14.42 versus 43.86+/-12.05, P=0.011), and in both, levels were significantly higher than the peripheral measurements.",
            "output": [
                "Are increased levels of basic fibroblast growth factor found in the cross-clamped heart during cardiopulmonary bypass?"
            ]
        },
        {
            "id": "task847-3f4be1cda473438699b1ef223dee0ce3",
            "input": "We determined whether milrinone, a phosphodiesterase III inhibitor, attenuates serotonin-induced (5-hydroxytryptamine [5HT]) pulmonary hypertension (PH) and bronchoconstriction. Dogs were anesthetized with pentobarbital (30 mg/kg + 2 mg. kg(-1). h(-1)). Bronchoconstriction and PH were elicited by 5HT (10 microg/kg + 1.0 mg. kg(-1). h(-1)). Pulmonary vascular resistance was used to assess PH. Bronchoconstriction was also assessed by changes in bronchial cross-sectional area obtained from our bronchoscopic method. At 30 min after 5HT infusion started, seven dogs were given milrinone: 0 (saline), 5, 50, 500, and 5000 microg/kg at 10-min intervals. The other 12 dogs were given milrinone 5000 microg/kg 30 min after 5HT infusion, and 5 min later were given propranolol 0.2 mg/kg (n = 6) or saline (n = 6) IV. The 5HT significantly increased percentage of pulmonary vascular resistance to 208% +/- 27% and decreased percentage of bronchial cross-sectional area to 52% +/- 5% of the basal. Milrinone significantly attenuated both PH and bronchoconstriction in a dose-dependent manner. However, -log 50% effective concentration (mean ED(50) in microg/kg) of milrinone for bronchoconstriction: 4.32 +/- 0.13 (47.6) was significantly smaller than that for PH: 3.84 +/- 0.29 (144.9) (P < 0.01). In addition, the spasmolytic effects of milrinone (5000 microg/kg) were not antagonized by propranolol, although this dose significantly increased plasma catecholamines. In conclusion, milrinone attenuates 5HT-induced PH and bronchoconstriction; however, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than in pulmonary vascular smooth muscle. In addition, the relaxant effects could not be caused by beta-adrenoceptor activation because beta-blocker did not antagonize.",
            "output": [
                "Does milrinone attenuate serotonin-induced pulmonary hypertension and bronchoconstriction in dogs?"
            ]
        },
        {
            "id": "task847-ef27fa44888740d782e5fe0d9f4e1303",
            "input": "Nonadherence with scheduled saliva sampling, as encountered in ambulatory settings, can bias the estimation of salivary cortisol concentrations. This study is the first to estimate if such nonadherence is also associated with biased salivary testosterone concentration estimates.', \"Using a standard ambulatory saliva-sampling protocol, we instructed pregnant women to collect saliva samples on two consecutive days at awakening, 1100h, 1500h, 2000h, and 2200h. We estimated testosterone concentrations in the saliva samples and participants' actual sampling times with an electronic medication event-monitoring system. We classified a saliva sample as adherent if it was sampled within a specific time window relative to its scheduled sampling time. We used a mixed-model analysis to distinguish between trait (number of adherent saliva samples per participant) and state (adherence status of a specific sample) adherence.\", \"We included 60 pregnant women in this study. Seventy-five percent (448 of 600) of the scheduled samples indicated adherence with the sampling schedule. Participants' trait adherence was associated with their diurnal profiles of salivary testosterone estimates; that is, adherent participants had higher salivary testosterone estimates compared with nonadherent participants, F(1,58)=5.41, p=0.023, Cohen's d=0.67. The state adherence of a sample was associated with the salivary testosterone estimate of the related sample, F(1,469)=4.48, p=0.035, Cohen's d=0.20, with delayed sampling associated with lower salivary testosterone estimates.",
            "output": [
                "Is nonadherence with ambulatory saliva sampling associated with biased salivary testosterone estimates?"
            ]
        },
        {
            "id": "task847-f30a9284f9314fb19702141f36e67860",
            "input": "High temperature is a major environmental factor limiting grape yield and affecting berry quality. Thermotolerance includes the direct response to heat stress and the ability to recover from heat stress. To better understand the mechanism of the thermotolerance of Vitis, we combined a physiological analysis with iTRAQ-based proteomics of Vitis vinifera cv Cabernet Sauvignon, subjected to 43\u00b0C for 6 h, and then followed by recovery at 25/18\u00b0C.', 'High temperature increased the concentrations of TBARS and inhibited electronic transport in photosynthesis apparatus, indicating that grape leaves were damaged by heat stress. However, these physiological changes rapidly returned to control levels during the subsequent recovery phase from heat stress. One hundred and seventy-four proteins were differentially expressed under heat stress and/or during the recovery phase, in comparison to unstressed controls, respectively. Stress and recovery conditions shared 42 proteins, while 113 and 103 proteins were respectively identified under heat stress and recovery conditions alone. Based on MapMan ontology, functional categories for these dysregulated proteins included mainly photosynthesis (about 20%), proteins (13%), and stress (8%). The subcellular localization using TargetP showed most proteins were located in the chloroplasts (34%), secretory pathways (8%) and mitochondrion (3%).",
            "output": [
                "Does differential proteomic analysis of grapevine leave by iTRAQ reveals responses to heat stress and subsequent recovery?"
            ]
        },
        {
            "id": "task847-7daea2d2bf904ba4abd2b892488d307a",
            "input": "To examine the regulatory aspects of zinc-\u03b12-glycoprotein (ZAG) association with obesity-related insulin resistance.', 'ZAG mRNA and protein were analyzed in subcutaneous adipose tissue (AT) and circulation of lean, obese, prediabetic, and type 2 diabetic men; both subcutaneous and visceral AT were explored in lean and extremely obese. Clinical and ex vivo findings were corroborated by results of in vitro ZAG silencing experiment.', 'Subcutaneous AT ZAG was reduced in obesity, with a trend to further decrease with prediabetes and type 2 diabetes. ZAG was 3.3-fold higher in subcutaneous than in visceral AT of lean individuals. All differences were lost in extreme obesity. Obesity-associated changes in AT were not paralleled by alterations of circulating ZAG. Subcutaneous AT ZAG correlated with adiposity, adipocyte hypertrophy, whole-body and AT insulin sensitivity, mitochondrial content, expression of GLUT4, PGC1\u03b1, and adiponectin. Subcutaneous AT ZAG and adipocyte size were the only predictors of insulin sensitivity, independent on age and BMI. Silencing ZAG resulted in reduced adiponectin, IRS1, GLUT4, and PGC1\u03b1 gene expression in primary human adipocytes.",
            "output": [
                "Is subcutaneous adipose tissue zinc-\u03b12-glycoprotein associated with adipose tissue and whole-body insulin sensitivity?"
            ]
        },
        {
            "id": "task847-6338c85cbb094a1590949322b651a42d",
            "input": "The relationship between excess weight gain and asthma in childhood remains inadequately defined. The aim of this study was to evaluate, as part of a prospective post-bronchiolitis follow-up, whether there is a link between earlier or current overweight or obesity and asthma or asthma symptoms at 5-7 years of age.', 'In all, 151 former bronchiolitis patients were followed-up until the mean age of 6.45 years. At the control visit, the weights and heights were measured, and the asthma symptoms and medications for asthma were recorded. The weight status was expressed as body mass index (BMI) z-scores (zBMI).', 'There were 10 obese and 31 overweight (zBMI over national references) children. In adjusted analyses, presence of current asthma at 6-7 years of age (aOR 3.05, 95% CI 1.02-9.93) differed between overweight and normal weight children. Further, asthma ever, asthma at age 4-5 years, asthma at age 5-6 years, use of bronchodilators ever and use of ICSs during the last 12 months were more common in currently overweight than in normal weight children. Obesity was associated only with current asthma and asthma ever. Instead, there were no significant associations between birth weight, excess weight gain in infancy, or overweight at age 1.5 years, and later asthma, asthma symptoms or use of asthma medication.",
            "output": [
                "Is excess weight in preschool children with a history of severe bronchiolitis associated with asthma?"
            ]
        },
        {
            "id": "task847-87c8ba2a3ac3491ca32b7828804ab585",
            "input": "Sentinel lymph node biopsy (SLNB) before mastectomy and immediate breast reconstruction (IBR) may help to avoid the negative cosmetic effects of radiotherapy on reconstructed breasts in lymph node-positive patients. Concerns have been raised regarding possible delays whilst awaiting the SLNB result prior to definitive surgery, which needs to be performed within 31 days of cancer diagnosis. The aim was to investigate whether initial SLNB delays mastectomy and IBR.', 'All patients who had IBR between January 2005 and 2007 were reviewed retrospectively. Before October 2005 axillary staging was performed simultaneously with mastectomy and IBR (Group I). After October 2005, SLNB was performed as an initial procedure and patients with positive SLNB were only offered a temporary tissue expander to be replaced by autogenous reconstruction after completing the cancer treatment (Group II). Date of diagnosis and waiting times were recorded and the two groups were compared. Different reasons for delays in treatment were studied.', 'One hundred and thirty-nine IBR (123 patients) were included in the statistical analysis (67 IBR in Group I and 72 IBR in Group II). Seventy-one patients (57.7%) had no delay (mean waiting time of 23 days). Fifty-two patients (42.3%) had delay longer than 31 days (mean waiting time of 66 days). Group I patients had a mean waiting time (standard deviation) of 38.8 (38) days and Group II patients 42.7 (24) days (p = 0.51).",
            "output": [
                "Does sentinel lymph node biopsy before mastectomy and immediate breast reconstruction significantly delay surgery in early breast cancer?"
            ]
        },
        {
            "id": "task847-5d26d5c6859f4009aca1d0ee37b09596",
            "input": "A third of the world's population does not engage in recommended levels of physical activity (PA), leading to substantial health and economic burdens. The healthcare sector offers a variety of resources that can help counsel, refer and deliver PA promotion programmes for purposes of primordial, primary, secondary and tertiary prevention. Substantial evidence already exists in support of multipronged PA counselling, prescription and referral strategies, in particular those linking healthcare and community-based resources.\", 'The Exercise is Medicine (EIM) initiative was introduced in 2007 to advance the implementation of evidence-based strategies to elevate the status of PA in healthcare. In this article, we describe the evolution and global expansion of the EIM initiative, its components, their implementation, an evaluation framework and future initiative activities.', 'Until now, EIM has a presence in 39 countries with EIM Regional Centers established in North America, Latin America, Europe, Africa, Southeast Asia, China and Australasia. The EIM Global Health Initiative is transitioning from its initial phase of infrastructure and awareness building to a phase of programme implementation, with an emphasis in low-to-middle income countries, where 80% of deaths due to non-communicable diseases already occur, but where a large gap in research and implementation of PA strategies exists.",
            "output": [
                "Is the Exercise Medicine Global Health Initiative : a 2014 update?"
            ]
        },
        {
            "id": "task847-3fc3df8d195543b8a317939cc458e14d",
            "input": "Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established.', 'Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N = 209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used to estimate associations.', 'Of note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI, 1.06-4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at biopsy).",
            "output": [
                "Is chronic inflammation in benign prostate tissue associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial?"
            ]
        },
        {
            "id": "task847-8059d62db1ac435baa4d7711a8de2401",
            "input": "To determine the effect of suppression of vascular endothelial growth factor (VEGF) by monthly injection of ranibizumab on posterior retinal nonperfusion (RNP) in patients with diabetic macular edema (DME).', 'Unplanned retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials.', 'Six hundred sixty-six patients with DME.', 'An independent reading center measured the area of RNP on fluorescein angiograms obtained in the phase 3 RISE and RIDE trials.', 'The percentage of patients with no posterior RNP.', 'The percentage of patients with no posterior RNP decreased in the sham group between baseline and month 24, but remained relatively stable in the 2 ranibizumab groups. After month 24, the sham group crossed over to receive monthly injections of ranibizumab 0.5 mg, and the differences between the sham and ranibizumab groups were reduced. The percentage of patients who showed an increase in posterior RNP from baseline increased over time in all 3 groups, but at a faster rate in the sham group, resulting in statistically significant differences at every time point between months 3 (9.6% vs. 18.5%; P = 0.016) and 24 (16.1% vs. 37.6%; P<0.0001) for ranibizumab 0.5 mg versus sham and from months 6 (12.3% vs. 23.0%; P = 0.013) through 24 (15.0% vs. 37.6%; P<0.0001) for ranibizumab 0.3 mg. Initiation of ranibizumab in the sham group at month 24 was followed by reduction in the percentage of patients with an increase in posterior RNP from baseline at months 30 and 36, whereas the 2 ranibizumab groups continued their gradual rise.",
            "output": [
                "Does neutralization of vascular endothelial growth factor slow progression of retinal nonperfusion in patients with diabetic macular edema?"
            ]
        },
        {
            "id": "task847-14381da4be9142baaca1468694188b8b",
            "input": "The goals of this study were to determine if \u03b2-acid from hops (Humulus lupulus L.) could be used to control fructan fermentation by equine hindgut micro-organisms, and to verify the antimicrobial mode of action on Streptococcus bovis, which has been implicated in fructan fermentation, hindgut acidosis and pasture-associated laminitis (PAL) in the horse.', 'Suspensions of uncultivated equine faecal micro-organisms produced fermentation acids when inulin (model fructan) was the substrate, but \u03b2-acid (i.e. lupulone) concentrations \u22659\\xa0ppm inhibited lactate production and mitigated the decrease in pH. Inulin-fermenting Strep.\\xa0bovis was isolated from the \u03b2-acid-free suspensions after enrichment with inulin. The isolates were sensitive to \u03b2-acid, which decreased the viable number of streptococci in faecal suspensions, as well as growth, lactate production and the intracellular potassium of Strep.\\xa0bovis in pure culture.",
            "output": [
                "Does inhibition of fructan-fermenting equine faecal bacteria and Streptococcus bovis by hop ( Humulus lupulus L. ) \u03b2-acid?"
            ]
        },
        {
            "id": "task847-444bd47593924ce6a67489df4d7dd711",
            "input": "Pain in infancy is a developmental process. Due to the underdeveloped pain pathways in the spinal cord, the threshold of stimulation and sensation of pain is low at birth and has potential impacts on increasing the central effects of pain. Primary trauma during infancy can cause long term changes in structure and function of pain pathways that continue until adulthood. Lack of pain management in children can result in morbidity and mortality.', 'In this study we examined the duration of post-operative analgesia in children when clonidine is added to bupivacaine in caudal anesthesia.', 'In this clinical trial, 40 children aged 1-8 years who were candidates for elective inguinal hernia repair were studied. Induction and maintenance of anesthesia were achieved using sodium thiopenthal, halothane and nitrous oxide. Children were randomly divided into 2 groups in a double-blind fashion, and were given caudal anesthesia with 0.125% bupivacaine (1ml/kg) alone or b bupivacaine plus 2 \u03bcg/kg clonidine. Blood pressure and heart rate were recorded peri-operatively. Analgesia was evaluated using objective pain scale (OPS) and sedation was assessed using Ramsay sedation scale (RSS). Acetaminophen was administered rectally for cases with OPS score greater than five.', 'Duration of analgesia was found to be significantly longer in the group given bupivacaine plus clonidine (mean 417.50 min vs. 162.00 min). Peri-operative hypotension or bradycardia, post-operative respiratory depression, nausea or vomiting were not recorded in any patient.",
            "output": [
                "Does addition of clonidine in caudal anesthesia in children increase duration of post-operative analgesia?"
            ]
        },
        {
            "id": "task847-0a7abdfd6ff9419ba8eb72da87adf4e4",
            "input": "Patients with alcoholic liver disease (ALD) display inflammation of the subcutaneous adipose tissue (SAT) which correlates with liver lesions. We examined macrophage markers and polarization in the SAT of alcoholic patients and adipokine expression according to liver inflammation; we studied the consequences of alcohol withdrawal.', 'Forty-seven patients with ALD were prospectively included. SAT and blood samples were collected at inclusion and after 1\\xa0week of alcohol withdrawal. Pro-inflammatory cytokines/chemokines, inflammasome components and products, adipokine expression levels, macrophage markers and polarization in liver and SAT samples were assessed by RT-PCR arrays.', 'mRNA expression level of chemokines (IL8, semaphorin 7A) correlated with hepatic steatosis in both liver and SAT. Liver expression of inflammasome components (IL1\u03b2, IL18, caspase-1) and SAT IL6 and CCL2 correlated with liver damage. In patients with mild ALD, 1\\xa0week of alcohol withdrawal was sufficient to decrease expression level of total macrophage markers in the adipose tissue, to orient adipose tissue macrophages (ATM) towards an anti-inflammatory M2 phenotype and to decrease the mRNA expression of cytokines/chemokines (IL18, CCL2, osteopontin, semaphorin 7A). In patients with severe ALD, 1\\xa0week of abstinence was also associated with an increase in CCL18 expression.",
            "output": [
                "Does alcohol withdrawal alleviate adipose tissue inflammation in patients with alcoholic liver disease?"
            ]
        },
        {
            "id": "task847-c1231dd0edcc4cbebb1927a5f870105c",
            "input": "Galectin-3 is a marker of myocardial fibrosis that has been implicated in the pathophysiologic pathway of fibrosis; its association with all-cause and cardiovascular disease (CVD) mortality in a community-based cohort free of baseline CVD has not been reported. Our aim was to determine the association between galectin-3 levels and all-cause and CVD mortality in community-dwelling older adults without known CVD.', 'We measured plasma galectin-3 levels in 1,393 Rancho Bernardo Study participants without CVD with a mean age of 70 years. Participants were followed up for a mean of 11 years for coronary heart disease, CVD mortality, and all-cause mortality.', 'During follow-up, 436 participants died (169 from CVD). In models adjusted for traditional CVD risk factors and renal function, galectin-3 was a significant predictor of CVD mortality (hazard ratio [HR] per SD log increase 1.30, 95% CI 1.10-1.53) and all-cause mortality (HR 1.12, 1.01-1.24), but not coronary heart disease (HR 1.09, 0.92-1.30). After further adjusting for N-terminal pro B-type natriuretic peptide, galectin-3 remained an independent predictor (HR 1.24, 1.05-1.47) of CVD mortality. Galectin-3 improved the c statistic (0.847-0.851, P = .003) for prediction of CVD death. Net reclassification improvement (>0) with the addition of galectin-3 was 35% (P < .0001); the integrated discrimination index was also significant (P = .03). Participants with both galectin-3 and N-terminal pro B-type natriuretic peptide above the median had increased risk of CVD death vs those with higher levels of only 1 of these markers (HR 1.74, 1.24-2.43).",
            "output": [
                "Is galectin-3 independently associated with cardiovascular mortality in community-dwelling older adults without known cardiovascular disease : The Rancho Bernardo Study?"
            ]
        },
        {
            "id": "task847-312b06bd147a49ea9280c54658cc5cbf",
            "input": "Multicentric fibroadenomas, defined as multiple fibroadenomas located at different quadrants of the breast, occur in 10-20% of women with fibroadenoma. The surgical management of multicentric fibroadenomas may be troublesome for surgeons and patients. In this study, we report our preliminary experience using the \"round block technique\" in the management of women with multicentric fibroadenomas of the breast.', \"Records of patients with breast diseases managed with the round block technique were searched for in the Changhua Christian Hospital oncoplastic breast surgery database. The patients' clinicopathologic characteristics, type of surgery, operation time, blood loss, and complications were recorded. The cosmetic outcome was evaluated by the patient and operating surgeon two months after the surgery.\", 'Twenty patients with multicentric fibroadenomas managed by the round block technique comprised the current study cohort. The mean age of the subjects was 36.5\\xa0\u00b1\\xa010.4 years. Twelve (60%) patients had tumors on one side of the breast, and eight (40%) had bilateral breast lesions. The average number of tumors removed was 3.3\\xa0\u00b1\\xa01.2 (range 2-6) per breast, and mean tumor size was 2.2\\xa0\u00b1\\xa00.5\\xa0cm. Three (15%) patients developed mild ecchymosis of the breast undergoing operation, which resolved spontaneously. One (5%) patient had partial nipple ischemia/necrosis due to 2 tumors excised near the nipple-areolar complex. The aesthetic results were evaluated as good in 19 (95%) patients and fair in 1 (5%).",
            "output": [
                "Is round block technique a useful oncoplastic procedure for multicentric fibroadenomas?"
            ]
        },
        {
            "id": "task847-c2d317123f85417ab60b1e65c411373c",
            "input": "To compare the rate of parastomal hernia in patients undergoing anterior fascial fixation of the ileal conduit with that in patients without fascial fixation. Limited data exist on whether anterior fascial fixation of the ileal conduit impacts the rate of parastomal hernia.', 'A total of 496 consecutive patients undergoing radical cystectomy and ileal conduit reconstruction from 1995 to 2012 were retrospectively evaluated for parastomal hernia. All patients had a 2-fingerbreadth aperture and the ileal conduit brought through the rectus muscle and sheath. Patients were divided into 1 of 3 groups based on stoma fixation and/or reinforcement: anterior fascial fixation, posterior reinforcement, or no fascial fixation. A parastomal hernia was defined as a palpable bulge at the stoma site. Multivariate logistic regression was conducted for the primary end point of parastomal hernia, controlling for other patient- and treatment-related factors that might affect the rate of parastomal hernia.', 'Median follow-up was 16 months (range, 1-189 months). The parastomal hernia rate was significantly greater in the anterior fascial suture group (43 of 281; 15.3%) than the no fascial suture group (12 of 164; 7.3%; P=.02). Multivariate logistic regression analysis modeled for the occurrence of a parastomal hernia demonstrated that anterior fascial fixation was an independent predictor of the development of parastomal hernia (odds ratio, 2.3; 95% confidence interval, 1.03-5.14; P=.04).",
            "output": [
                "Does anterior fascial fixation reduce the parastomal hernia rate after radical cystectomy and ileal conduit?"
            ]
        },
        {
            "id": "task847-ee9a5f4d3454455689190d761b9737d1",
            "input": "Flat and depressed lesions are becoming increasingly recognized in the esophagus, stomach, and colon. Various techniques have been described for endoscopic mucosal resection (EMR) of these lesions.', 'To evaluate the efficacy of lift-grasp-cut EMR using a prototype dual-channel forward-viewing endoscope with an instrument elevator in one accessory channel (dual-channel elevator scope) as compared to standard dual-channel endoscopes.', 'EMR was performed using a lift-grasp-cut technique on normal flat rectosigmoid or gastric mucosa in live porcine models after submucosal injection of 4 mL of saline using a dual-channel elevator scope or a standard dual-channel endoscope. With the dual-channel elevator scope, the elevator was used to attain further lifting of the mucosa. The primary endpoint was size of the EMR specimen and the secondary endpoint was number of complications.', 'Twelve experiments were performed (six gastric and six colonic). Mean specimen diameter was 2.27 cm with the dual-channel elevator scope and 1.34 cm with the dual-channel endoscope (P = 0.018). Two colonic perforations occurred with the dual-channel endoscope, vs no complications with the dual-channel elevator scope.",
            "output": [
                "Does use of prototype two-channel endoscope with elevator enable larger lift-and-snare endoscopic mucosal resection in a porcine model?"
            ]
        },
        {
            "id": "task847-cc9bd1548aee4b64bb5d3c4fcd43b97d",
            "input": "We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabetes mellitus (T2DM).', 'Serum PON-1 (arylesterase activity) and HDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 67 T2DM patients and in 56 non-diabetic subjects.', 'PON-1 activity, HDL cholesterol and apoA-I were decreased in T2DM (all p<0.05). The HDL particle concentration was unaltered, but large HDL particles, medium HDL particles and HDL particle size were decreased, whereas small HDL particles were increased in T2DM (all p<0.05). PON-1 was more closely related to HDL cholesterol than to apoA-I (p=0.001). In turn, the positive relationship of PON-1 with the HDL particle concentration and with large HDL particles was stronger than that with HDL cholesterol (both p<0.01). The inverse relationship of PON-1 with T2DM was only modestly attenuated by HDL cholesterol or HDL particle characteristics.",
            "output": [
                "Is serum paraoxonase-1 activity more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects?"
            ]
        },
        {
            "id": "task847-340d1b71d09c4fd4879395d593f75a7e",
            "input": "Platelets are a natural source of growth factors, cytokines and chemokines, that regulate angiogenesis and inflammation. It has been suggested that differential release of pro- and anti-angiogenic growth factors from platelet \u03b1-granules by protease-activated receptors (PAR) 1 and 4 may be important for the regulation of angiogenesis. We aimed to compare the releasates of unstimulated platelets with PAR-1- and PAR-4-stimulated platelets.', \"The release of \u03b2-thromboglobulin, platelet factor (PF)-4, thrombospondin, platelet-derived growth factor (PDGF)-A/B, regulated and normal T-cell expressed and secreted (RANTES/CCL5), endostatin, CXCL12, and vascular endothelial growth factor (VEGF) was measured with enzyme-linked immunosorbent assay (ELISA). Mass spectrometry (MS)-based quantitative proteomics identified 93 proteins from platelets stimulated with PAR-1 and PAR-4. A strong correlation between the factors released after either stimulus was observed (Spearman's r 0.94, P < 0.001). Analysis with ELISA showed that stimulation with PAR-1 or PAR-4 lead to non-differential release of \u03b2-thromboglobulin, PF-4, thrombospondin, PDGF-A/B, RANTES/CCL5, endostatin, CXCL12, and VEGF. Release of thrombospondin was slightly lower after PAR-1 stimulation (7.2 \u03bcg/mL), compared with PAR-4 induced release (9.8 \u03bcg/mL; P < 0.05).",
            "output": [
                "Does quantitative proteomics analysis reveal similar release profiles following specific PAR-1 or PAR-4 stimulation of platelets?"
            ]
        },
        {
            "id": "task847-d5e1f692ebff4deb8f687d1d83957144",
            "input": "Tumour necrosis factor-\u03b1 (TNF-\u03b1) plays a key role in the regulation of cardiac contractility. Although cardiomyocytes are known to express the TNF-\u03b1 receptors (TNFRs), the mechanism of TNF-\u03b1 signal transmission is incompletely understood. The aim of this study was to investigate whether the tumour suppressor Ras-association domain family protein 1 isoform A (RASSF1A) modulates TNF-\u03b1 signalling in cardiomyocytes.', \"We used RASSF1A knockout (RASSF1A(-/-)) mice and wild-type (WT) littermates in this study. Acute stimulation with a low dose of TNF-\u03b1 (10 \u00b5g/kg iv) increased cardiac contractility and intracellular calcium transients' amplitude in WT mice. In contrast, RASSF1A(-/-) mice showed a blunted contractile response. Mechanistically, RASSF1A was essential in the formation of the TNFR complex (TNFRC), where it functions as an adaptor molecule to facilitate the recruitment of TNFR type 1-associated death domain protein and TNFR-associated factor 2 to form the TNF-\u03b1 receptor complex. In the absence of RASSF1A, signal transmission from the TNF-\u03b1 receptor complex to the downstream effectors, such as cytoplasmic phospholipase A2 and protein kinase A, was attenuated leading to the reduction in the activation of calcium handling molecules, such as L-type Ca(2+) channel and ryanodine receptors.",
            "output": [
                "Does the tumour suppressor Ras-association domain family protein 1A ( RASSF1A ) regulate TNF-\u03b1 signalling in cardiomyocytes?"
            ]
        },
        {
            "id": "task847-a3a4ba13a31d4923a2fd289070b0a500",
            "input": "The H2.0-like homeobox transcription factor (HLX) plays an essential role in visceral organogenesis in mice and has been shown to regulate angiogenic sprouting in vitro and in zebrafish embryos. We therefore examined the role of HLX in vascular development in mouse and avian embryos.', 'In situ hybridization showed that Hlx is expressed in a subset of sprouting blood vessels in postnatal mouse retinas and embryos. Hlx expression was conserved in quail embryos and upregulated in blood vessels at the onset of circulation. In vitro assays showed that Hlx is dynamically regulated by growth factors and shear stress alterations. Proangiogenic vascular endothelial growth factor induces Hlx expression in cultured endothelial cells, whereas signals that induce stalk cell identity lead to a reduction in Hlx expression. HLX was also downregulated in embryos in which flow was ablated, whereas injection of a starch solution, which increases blood viscosity and therefore shear stress, causes an upregulation in HLX. HLX knockdown in vitro resulted in a reduction in tip cell marker expression and in reduced angiogenic sprouting, but Hlx(-/-) embryos showed no defect in vascular sprouting at E8.5, E9.5, or E11.5 in vivo. Vascular remodeling of the capillary plexus was altered in Hlx(-/-) embryos, with a modestly enlarged venous plexus and reduction of the arterial plexus.",
            "output": [
                "Does the H2.0-like homeobox transcription factor modulate yolk sac vascular remodeling in mouse embryos?"
            ]
        },
        {
            "id": "task847-e77b7fdffe564d4f8f0cde84389ebf22",
            "input": "Neutrophil infiltration of the postischemic tissue considerably contributes to organ dysfunction on ischemia/reperfusion injury. Beyond its established role in fibrinolysis, tissue-type plasminogen activator (tPA) has recently been implicated in nonfibrinolytic processes. The role of this serine protease in the recruitment process of neutrophils remains largely obscure.', 'Using in vivo microscopy on the postischemic cremaster muscle, neutrophil recruitment and microvascular leakage, but not fibrinogen deposition at the vessel wall, were significantly diminished in tPA(-/-) mice. Using cell transfer techniques, leukocyte and nonleukocyte tPA were found to mediate ischemia/reperfusion-elicited neutrophil responses. Intrascrotal but not intra-arterial application of recombinant tPA induced a dose-dependent increase in the recruitment of neutrophils, which was significantly higher compared with stimulation with a tPA mutant lacking catalytic activity. Whereas tPA-dependent transmigration of neutrophils was selectively reduced on the inhibition of plasmin or gelatinases, neutrophil intravascular adherence was significantly diminished on the blockade of mast cell activation or lipid mediator synthesis. Moreover, stimulation with tPA caused a significant elevation in the leakage of fluorescein isothiocyanate dextran to the perivascular tissue, which was completely abolished on neutrophil depletion. In vitro, tPA-elicited macromolecular leakage of endothelial cell layers was abrogated on the inhibition of its proteolytic activity.",
            "output": [
                "Does tissue plasminogen activator promote postischemic neutrophil recruitment via its proteolytic and nonproteolytic properties?"
            ]
        },
        {
            "id": "task847-484df0f3a9514fec862dcc9aa0b7f5ec",
            "input": "Bruton's tyrosine kinase (Btk) is required for B lymphocyte and myeloid cell contributions to pathology in murine models of arthritis. Here, we examined the potential contributions of synovial Btk expression and activation to inflammation in rheumatoid arthritis (RA).\", 'Btk was detected by immunohistochemistry and digital image analysis in synovial tissue from biologically naive RA (n=16) and psoriatic arthritis (PsA) (n=12) patients. Cell populations expressing Btk were identified by immunofluorescent double labelling confocal microscopy, quantitative (q-) PCR and immunoblotting. The effects of a Btk-specific inhibitor, RN486, on gene expression in human macrophages and RA synovial tissue explants (n=8) were assessed by qPCR, ELISA and single-plex assays.', 'Btk was expressed at equivalent levels in RA and PsA synovial tissue, restricted to B lymphocytes, monocytes, macrophages and mast cells. RN486 significantly inhibited macrophage IL-6 production induced by Fc receptor and CD40 ligation. RN486 also reduced mRNA expression of overlapping gene sets induced by IgG, CD40 ligand (CD40L) and RA synovial fluid, and significantly suppressed macrophage production of CD40L-induced IL-8, TNF, MMP-1 and MMP-10, LPS-induced MMP-1, MMP-7 and MMP-10 production, and spontaneous production of IL-6, PDGF, CXCL-9 and MMP-1 by RA synovial explants.",
            "output": [
                "Does btk inhibition suppress agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants?"
            ]
        },
        {
            "id": "task847-f9989f52f5bb4811b81a0c56842483fe",
            "input": "Chronic alcohol intake affects liver function and causes hepatic pathological changes. It has been shown that peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1)-null mice developed more pronounced hepatic changes than wild-type (WT) mice after chronic exposure to a diet containing 4% alcohol. The remarkable similarity between the histopathology of alcoholic liver disease (ALD) in Ppara-null model and in humans, and the fact that PPAR\u03b1 expression and activity in human liver are less than one-tenth of those in WT mouse liver make Ppara-null a good system to investigate ALD.', 'In this study, the Ppara-null model was used to elucidate the dynamic regulation of PPAR\u03b1 activity during chronic alcohol intake. Hepatic transcriptomic and metabolomic analyses were used to examine alterations of gene expression and metabolites associated with pathological changes. The changes triggered by alcohol consumption on gene expression and metabolites in Ppara-null mice were compared with those in WT mice.', 'The results showed that in the presence of PPAR\u03b1, 3 major metabolic pathways in mitochondria, namely the fatty acid \u03b2-oxidation, the tricarboxylic acid cycle, and the electron transfer chain, were induced in response to a 2-month alcohol feeding, while these responses were greatly reduced in the absence of PPAR\u03b1. In line with the transcriptional modulations of these metabolic pathways, a progressive accumulation of triglycerides, a robust increase in hepatic cholic acid and its derivatives, and a strong induction of fibrogenesis genes were observed exclusively in alcohol-fed Ppara-null mice.",
            "output": [
                "Does modulation of fatty acid and bile acid metabolism by peroxisome proliferator-activated receptor \u03b1 protect against alcoholic liver disease?"
            ]
        },
        {
            "id": "task847-b48410d330cd4fa8a53e79afb22b5bc7",
            "input": "Chronic inflammation and oxidative stress are key features of chronic obstructive pulmonary disease (COPD). Oxidative stress enhances COPD inflammation under the control of the pro-inflammatory redox-sensitive transcription factor nuclear factor-kappaB (NF-\u03baB). Histone acetylation plays a critical role in chronic inflammation and bromodomain and extra terminal (BET) proteins act as \"readers\" of acetylated histones. Therefore, we examined the role of BET proteins in particular Brd2 and Brd4 and their inhibitors (JQ1 and PFI-1) in oxidative stress- enhanced inflammation in human bronchial epithelial cells.', 'Human primary epithelial (NHBE) cells and BEAS-2B cell lines were stimulated with IL-1\u03b2 (inflammatory stimulus) in the presence or absence of H2O2 (oxidative stress) and the effect of pre-treatment with bromodomain inhibitors (JQ1 and PFI-1) was investigated. Pro-inflammatory mediators (CXCL8 and IL-6) were measured by ELISA and transcripts by RT-PCR. H3 and H4 acetylation and recruitment of p65 and Brd4 to the native IL-8 and IL-6 promoters was investigated using chromatin immunoprecipitation (ChIP). The impact of Brd2 and Brd4 siRNA knockdown on inflammatory mediators was also investigated.', 'H2O2 enhanced IL1\u03b2-induced IL-6 and CXCL8 expression in NHBE and BEAS-2B cells whereas H2O2 alone did not have any affect. H3 acetylation at the IL-6 and IL-8 promoters was associated with recruitment of p65 and Brd4 proteins. Although p65 acetylation was increased this was not directly targeted by Brd4. The BET inhibitors JQ1 and PFI-1 significantly reduced IL-6 and CXCL8 expression whereas no effect was seen with the inactive enantiomer JQ1(-). Brd4, but not Brd2, knockdown markedly reduced IL-6 and CXCL8 release. JQ1 also inhibited p65 and Brd4 recruitment to the IL-6 and IL-8 promoters.",
            "output": [
                "Is brd4 essential for IL-1\u03b2-induced inflammation in human airway epithelial cells?"
            ]
        },
        {
            "id": "task847-a1ac12866d914789a5f255c98b430949",
            "input": "Distant prostate cancers are commonly hormone refractory and exhibit increased growth no longer inhibited by androgen deprivation therapy. Understanding all molecular mechanisms contributing to uncontrolled growth is important to obtain effective treatment strategies for hormone refractory prostate cancers (HRPC). The aryl hydrocarbon receptor (AhR) affects a number of biological processes including cell growth and differentiation. Several studies have revealed that exogenous AhR ligands inhibit cellular proliferation but recent evidence suggests AhR may possess intrinsic functions that promote cellular proliferation in the absence of exogenous ligands.', 'qRT-PCR and western blot analysis was used to determine AhR mRNA and protein expression in hormone sensitive LNCaP cells as well as hormone refractory DU145, PC3 and PC3M prostate cancer cell lines. LNCaP cells express AhR mRNA and protein at a much lower level than the hormone refractory cell models. Cellular fractionation and immunocytochemistry revealed nuclear localization of AhR in the established hormone refractory cell lines while LNCaP cells are devoid of nuclear AhR protein. qRT-PCR analysis used to assess basal CYP1B1 levels and a xenobiotic responsive element binding assay confirmed ligand independent transcriptional activity of AhR in DU145, PC3 and PC3M cells. Basal CYP1B1 levels were decreased by treatment with specific AhR inhibitor, CH223191. An in vitro growth assay revealed that CH223191 inhibited growth of DU145, PC3 and PC3M cells in an androgen depleted environment. Immunohistochemical staining of prostate cancer tissues revealed increased nuclear localization of AhR in grade 2 and grade 3 cancers compared to the well differentiated grade 1 cancers.",
            "output": [
                "Is the aryl hydrocarbon receptor constitutively active in advanced prostate cancer cells?"
            ]
        },
        {
            "id": "task847-fb6da5f91a1e456796ef19d8d3e5826c",
            "input": "Phosphodiesterase 2A (PDE2A) is an evolutionarily conserved enzyme that catalyzes the degradation of the cyclic nucleotides, cyclic adenosine monophosphate, and/or cyclic guanosine monophosphate. Recent studies reported the expression of PDE2A in the dorsal horn of the spinal cord, pointing to a potential contribution to the processing of pain. However, the functions of PDE2A in spinal pain processing in vivo remained elusive.', 'Immunohistochemistry, laser microdissection, and quantitative real-time reverse transcription polymerase chain reaction experiments were performed to characterize the localization and regulation of PDE2A protein and messenger RNA in the mouse spinal cord. Effects of the selective PDE2A inhibitor, BAY 60-7550 (Cayman Chemical, Ann Arbor, MI), in animal models of inflammatory pain (n = 6 to 10), neuropathic pain (n = 5 to 6), and after intrathecal injection of cyclic nucleotides (n = 6 to 8) were examined. Also, cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in spinal cord tissues were measured by liquid chromatography tandem mass spectrometry.', 'The authors here demonstrate that PDE2A is distinctly expressed in neurons of the superficial dorsal horn of the spinal cord, and that its spinal expression is upregulated in response to hind paw inflammation. Administration of the selective PDE2A inhibitor, BAY 60-7550, increased the nociceptive behavior of mice in animal models of inflammatory pain. Moreover, BAY 60-7550 increased the pain hypersensitivity induced by intrathecal delivery of cyclic adenosine monophosphate, but not of cyclic guanosine monophosphate, and it increased the cyclic adenosine monophosphate levels in spinal cord tissues.",
            "output": [
                "Does phosphodiesterase 2A localized in the spinal cord contribute to inflammatory pain processing?"
            ]
        },
        {
            "id": "task847-d7a60e76c2cb437aa519df082ae55aea",
            "input": "General anesthesia induces long-lasting cognitive and learning deficits. However, the underlying mechanism remains unknown. The GluA1 subunit of AMPAR is a key molecule for learning and synaptic plasticity, which requires trafficking of GluA1-containing AMPARs into the synapse.', 'Adult male rats were exposed to 1.8% isoflurane for 2 h and subjected to an inhibitory avoidance task, which is a hippocampus-dependent contextual fear learning paradigm (n = 16 to 39). The in vitro extracellular field potential of hippocampal synapses between the Schaffer collateral and the CA1 was evaluated using a multielectrode recorder (n = 6 per group). GluA1 expression in the synaptoneurosome was assessed using Western blotting (n = 5 to 8). The ubiquitination level of GluA1 was evaluated using immunoprecipitation and Western blotting (n = 7 per group).', 'Seven days after exposure to 1.8% isoflurane for 2 h (Iso1.8), the inhibitory avoidance learning (control vs. Iso1.8; 294 \u00b1 34 vs. 138 \u00b1 28, the mean \u00b1 SEM [%]; P = 0.002) and long-term potentiation (125.7 \u00b1 6.1 vs. 105.7 \u00b1 3.3; P < 0.001) were impaired. Iso1.8 also temporarily increased GluA1 in the synaptoneurosomes (100 \u00b1 9.7 vs. 138.9 \u00b1 8.9; P = 0.012) and reduced the GluA1 ubiquitination, a main degradation pathway of GluA1 (100 \u00b1 8.7 vs. 71.1 \u00b1 6.1; P = 0.014).",
            "output": [
                "Does isoflurane impair learning and hippocampal long-term potentiation via the saturation of synaptic plasticity?"
            ]
        },
        {
            "id": "task847-7ae076a4bf0f4194bffbb0c4d679b995",
            "input": "The risk of breast cancer in carriers of BRCA1 and BRCA2 mutations is influenced by factors other than the genetic mutation itself. Modifying factors include a woman's reproductive history and family history of cancer. Risk factors are more likely to be present in women with breast cancer than in women without breast cancer, and therefore the risk of cancer in the two breasts should not be independent. It is not clear to what extent modifying factors influence the risk of a first primary or a contralateral breast cancer in BRCA carriers.\", 'We conducted a matched case-control study of breast cancer among 3920 BRCA1 or BRCA2 mutation carriers. We asked whether a past history of breast cancer in the contralateral breast was a risk factor for breast cancer.', 'After adjustment for age, country of residence, and cancer treatment, a previous cancer of the right breast was found to be a significant risk factor for cancer of the left breast among BRCA1 or BRCA2 carriers (relative risk: 2.1; 95% confidence interval: 1.4 to 3.0; p < 0.0001).",
            "output": [
                "Is a prior diagnosis of breast cancer a risk factor for breast cancer in BRCA1 and BRCA2 carriers?"
            ]
        },
        {
            "id": "task847-1d89dac347524214ac9133113f1611ae",
            "input": "To investigate the contribution of muscle mass and handgrip strength in predicting the functional outcome after hip fracture in women.', 'Observational study.', 'Rehabilitation hospital.', 'White women (N=123 of 149) who were consecutively admitted to a rehabilitation hospital because of their first fracture of the hip.', 'Not applicable.', 'We measured appendicular lean mass (aLM) by dual-energy x-ray absorptiometry (DXA) 21.1 \u00b1 8.7 (mean \u00b1 SD) days after hip fracture occurrence in the 123 women. On the same day, we assessed grip strength at the nondominant arm with a dynamometer. At the end of acute inpatient rehabilitation we measured the ability to function in activities of daily living by using the Barthel Index, and lower limb performance by using the Timed Up and Go (TUG) test.', 'We found significant correlations between handgrip strength measured before rehabilitation and Barthel Index scores after rehabilitation (\u03c1=.50; P<.001), Barthel Index effectiveness (\u03c1=.45; P<.001), and the TUG test (\u03c1=-.41; P<.001). Conversely, we found no significant correlations between aLM/height(2) and Barthel Index scores after rehabilitation (\u03c1=.075; P=.41), Barthel Index effectiveness (\u03c1=.06; P=.53), or the TUG test (\u03c1=.005; P=.96). Significant associations between grip strength and all the outcome measures persisted after adjustment for 8 potential confounders, including Barthel Index scores before rehabilitation, age, number of medications, number of comorbidities, pressure ulcers, concomitant infections, time between fracture occurrence and assessment, and aLM/height(2).",
            "output": [
                "Is handgrip strength but not appendicular lean mass an independent predictor of functional outcome in hip-fracture women : a short-term prospective study?"
            ]
        },
        {
            "id": "task847-83d40c23fff04a6aa6c37f42e15455b4",
            "input": "Indoleamine 2,3 dioxygenase (IDO) degrades the essential amino acid tryptophan and has been shown to minimize rejection in animal models of renal transplantation. Ischemia-reperfusion injury (IRI) is unavoidable in renal transplantation and correlates with shorter graft survival times. Despite its favorable effects on rejection, there is evidence that IDO may facilitate renal IRI. Differentiating the negative impact of IDO on IRI from its pro-tolerant effects in allograft rejection is of clinical relevance. In these studies we hypothesized that constitutive IDO activity may influence renal genes associated with recovery from IRI, and that IDO inhibition may unmask these effects.', 'We examined the renal transcriptome in a rat model of IRI with and without IDO inhibition with 1-methyl-d-tryptophan (1-MT), and assessed for alterations in the gene expression signature.', 'These studies demonstrated that during recovery from renal IRI, pre-treatment with 1-MT alleviated alterations in 105 coding sequences associated with IRI, and in turn triggered new changes in 66 non-coding transcripts, the majority of which were represented by small nucleolar RNA.",
            "output": [
                "Does indoleamine 2,3-dioxygenase inhibition alter the non-coding RNA transcriptome following renal ischemia-reperfusion injury?"
            ]
        },
        {
            "id": "task847-14ca70e1de6c4ec7a4bdc6e752fcfff4",
            "input": "To investigate whether the aberrant expression of microRNA (miR)-196a and miR-196b can be used as potential prognostic markers of human osteosarcoma.', \"Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression levels of miR-196a and miR-196b in osteosarcoma tissues and patients' sera.\", 'Expression levels of miR-196a and miR-196b in osteosarcoma tissues were both significantly higher than those in noncancerous bone tissues (both p<0.001), in line with which, the serum levels of the two miRNAs were also markedly upregulated in patients with osteosarcomas compared with healthy controls (both p<0.001). Then, the elevation of serum miR-196a and miR-196b levels both more frequently occurred in osteosarcoma patients with high tumor grade (p=0.008 and 0.01, respectively), positive metastasis (p=0.001 and 0.006, respectively) and recurrence (p=0.001 and 0.006, respectively). Moreover, high serum miR-196a, high serum miR-196b and conjoined expression of miR-196a/miR-196b were all independent prognostic factors for OS (overall survival) and DFS (disease-free survival) of osteosarcoma patients.",
            "output": [
                "Does combined elevation of microRNA-196a and microRNA-196b in sera predict unfavorable prognosis in patients with osteosarcomas?"
            ]
        },
        {
            "id": "task847-86162729e8eb456982fba029c0456810",
            "input": "Trauma centers are currently benchmarked on mortality outcomes alone. However, pay-for-performance measures may financially penalize centers based on complications. Our objective was to determine whether the results would be similar to the current standard method of mortality-based benchmarking if trauma centers were profiled on complications.', 'We analyzed data from the National Trauma Data Bank from 2007 to 2010. Patients 16 years or older with blunt or penetrating injuries and an Injury Severity Score (ISS) of 9 or higher were included. Risk-adjusted observed-to-expected (O/E) mortality ratios for each center were generated and used to rank each facility as high, average, or low performing. We similarly ranked facilities on O/E morbidity ratios defined as occurrence of any major complication. Concordance between hospital performance rankings was evaluated using a weighted \u03ba statistic. Correlation between morbidity- and mortality-based O/E ratios was assessed using Pearson coefficients. Sensitivity analyses were performed to mitigate the competing risk of death for the morbidity analyses.', 'A total of 449,743 patients from 248 facilities were analyzed. The unadjusted morbidity and mortality rates were 10.0% and 6.9%, respectively. No correlation was found between morbidity- and mortality-based O/E ratios (r = -0.01). Only 40% of the centers had similar performance rankings for both mortality and morbidity. Of the 31 high performers for mortality, only 11 centers were also high performers for morbidity. A total of 78 centers were ranked as average, and 11 ranked as low performers on both outcomes. Comparison of hospital performance status using mortality and morbidity outcomes demonstrated poor concordance (weighted \u03ba = 0.03, p = 0.22).",
            "output": [
                "Does benchmarking trauma centers on mortality alone reflect quality of care : implications for pay-for-performance?"
            ]
        },
        {
            "id": "task847-bfcedad2ee024ccfbcf442001100e091",
            "input": "The most important factor for the selection of an umbilical cord blood unit (CBU) for hematopoietic stem cell transplantation is the total nucleated cell (TNC) count as a surrogate marker for stem cell content in the CBU. At present, about one in five donors can provide a CBU with a sufficient TNC count for umbilical cord blood (UCB) banking. It is labor-intensive to obtain consent of all eligible donors and optimization of the selection is needed. The purpose of this study was to investigate prenatal clinical predictors for TNC count that would help to identify successful UCB donors already on admission to the delivery unit.', 'This study was a retrospective analysis of 758 cryopreserved CBUs, collected from 2002 to 2006. Maternal and fetal factors analyzed were maternal age, gravidity, parity, weight, height, diabetes, premature rupture of membranes, gestational age, fetal sex, and birthweight. The impact on a high TNC count (<150 \u00d7 10(7) vs. \u2265 150 \u00d7 10(7)) of the CBU was modeled in a multivariate analysis model.', 'Fetal birthweight was the strongest predictor (p < 0.001) of TNC count of at least 150 \u00d7 10(7). With a composite score of parity, gestational week, maternal weight and height, fetal sex, and birthweight, a nomogram was developed that increased banking rates from 22.7% to 31.9% while decreasing the number of banked CBUs from 149 to 79.",
            "output": [
                "Does a prenatal prediction model for total nucleated cell count increase the efficacy of umbilical cord blood banking?"
            ]
        },
        {
            "id": "task847-a79ce6874212440d97d3a18bc23ef488",
            "input": "The LAP Mentor is a procedural simulator that provides a stepwise training for laparoscopic cholecystectomy. This study addresses its \"construct\" validity that is present when a simulator is able to discriminate between persons with known differences in performance level on the laparoscopic cholecystectomy in real life.', 'Three groups with different skill levels performed 2 trials of 4 distinct parts of the cholecystectomy procedure (cholecystectomy exercises) and 1 full procedure on the LAP Mentor. Assessment parameters concerning the quantity and the quality of performance were compared between groups using the Kruskal-Wallis and Mann-Whitney U tests.', 'The entire research was performed in the Center for Surgical Technologies, Leuven, Belgium.', 'For study purposes, 5 expert abdominal laparoscopists (>100 laparoscopic cholecystectomies performed), 11 surgical residents (10-30 cholecystectomies performed), and 10 novices (minimal laparoscopic experience) were recruited.', 'With regard to the quantity of performance (time needed and number of movements), the experts showed significantly better results compared with the novices in the cholecystectomy exercises. Only in the full procedure, the results of all the parameters (except speed) were significantly different between the 3 groups, with the best results observed for the experts and worst for the novices. With respect to quality of performance, only the parameter \"accuracy rate of dissection\" in exercise 3 showed significantly better performance by the experts.",
            "output": [
                "Does assessment of procedural skills using virtual simulation remain a challenge?"
            ]
        },
        {
            "id": "task847-bc8bd9a641634fbf9ee6831ad38c0d0c",
            "input": "Morus alba, a medicinal plant in Asia, has been used traditionally to treat diabetes mellitus and hypoglycemia. However, the effects of M. alba extract (MAE) on atopic dermatitis have not been verified scientifically. We investigated the effects of MAE on atopic dermatitis through in vitro and in vivo experiments.', 'We evaluated the effects of MAE on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7, as well as thymus and activation-regulated chemokine (TARC/CCL17) in HaCaT cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for four weeks, and the protective effects of MAE were investigated by measuring the severity of the skin reaction on the back and ears, the plasma levels of immunoglobulin E (IgE) and histamine, and histopathological changes in the skin on the back and ears.', 'MAE suppressed the production of NO and PGE2 in RAW 264.7 cells, as well as TARC in HaCaT cells, in a dose-dependent manner. MAE treatment of NC/Nga mice reduced the severity of dermatitis and the plasma levels of IgE and histamine. MAE also reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration in the skin on the back and ears.",
            "output": [
                "Does morus alba L. suppress the development of atopic dermatitis induced by the house dust mite in NC/Nga mice?"
            ]
        },
        {
            "id": "task847-0fb35872e6f9461d9bfb08ad9557ddd2",
            "input": "Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2\u03b1 and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver.', 'The study was performed in 264 consecutive patients referred for suspected metabolic disease. Steatosis was defined according to Hamaguchi ultrasonographic criteria. Oxidative stress was assessed by urinary 8-iso- prostaglandin F2\u03b1 and serum soluble NOX2-derived peptide levels.', 'Patients with non-alcoholic fatty liver had higher (p\\u2009<\\u20090.001) mean values of urinary 8-iso-PGF2\u03b1 and of serum soluble NOX2-derived peptide, alanine aminotransferase, Cytokeratin-18 and homeostasis model of insulin resistance and lower values of serum adiponectin as compared to those without. Prevalence of metabolic syndrome and of its clinical features was significantly higher in patients with non-alcoholic fatty liver. Same findings were also observed after the exclusion of obese subjects, or subjects with diabetes or with metabolic syndrome and in those not taking statin medication. In addition, the levels of urinary 8-iso-PGF2\u03b1 were independent predictors of non-alcoholic fatty liver and a strong association of urinary 8-iso-PGF2\u03b1 and of serum soluble NOX2-derived peptide with the severity of steatosis at ultrasound was also observed.",
            "output": [
                "Is nOX2-generated oxidative stress associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease?"
            ]
        },
        {
            "id": "task847-f02ab000eabc4a3c943e9df05c222be9",
            "input": "To determine if early pregnancy serum biomarkers in high-risk women who develop preeclampsia vary according to risk factor.', 'We performed a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in high-risk women. Serum biomarker levels at enrollment (before initiation of aspirin or placebo) were compared between women who did and did not develop preeclampsia, both for the group as a whole and within each of 4 high-risk groups (insulin-dependent diabetes, hypertension, multiple gestation, and previous preeclampsia) using a regression model adjusting for gestational age at collection and prepregnancy body mass index.', '1258 women were included (233 with insulin-dependent diabetes, 387 with chronic hypertension, 315 with a multiple gestation, 323 with previous preeclampsia). Multiple early pregnancy serum biomarkers differed between women who did and did not develop preeclampsia. Each high-risk group had a unique and largely nonoverlapping pattern of biomarker abnormality. Differences between those who did and did not develop preeclampsia were noted in vascular cell adhesion molecule in the diabetes group; human chorionic gonadotropin, soluble tumor necrosis factor receptor-2, tumor necrosis factor-alpha, selectin and angiogenin in the chronic hypertension group; interleukin-6, placental growth factor, soluble fms-like tyrosine kinase plus endoglin to placental growth factor ratio in the multiple gestation group; and angiogenin in the previous preeclampsia group.",
            "output": [
                "Is preeclampsia in high risk women characterized by risk group-specific abnormalities in serum biomarkers?"
            ]
        },
        {
            "id": "task847-c66e59166bc244888bb5ca42eb7d891b",
            "input": "Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on susceptibility and disease severity of IPD in previously healthy children aged <5 years.', 'IPD cases were identified through national registries. DNA was obtained from the Danish Neonatal Screening Biobank. Pneumococcal serotypes were determined by Quellung reaction. The associations between MBL2 diplotypes and IPD susceptibility, serotypes, and outcome were investigated using logistic regression analysis.', 'We included 372 cases with meningitis, 907 with bacteremia, and 1263 age- and sex-matched controls; 2372 individuals were successfully genotyped and assigned MBL2 diplotypes. The median age in our combined case series was 13 months. Children with defective diplotypes were not at higher risk for meningitis than children with other diplotypes (odds ratio [OR], 0.85; 95% confidence interval [CI], .56-1.28). Similar results were found for bacteremia (OR, 0.89; 95% CI, .68-1.15) as well as for all cases (OR, 0.87; 95% CI, .70-1.09). There was no association with susceptibility to recurrent IPD (n = 12) for children with defective diplotypes compared with cases with a single episode (OR, 0.53; 95% CI, .07-4.13) and with all controls (OR, 0.46; 95% CI, .06-3.56). There was no association between diplotypes and mortality or between diplotypes and pneumococcal serotypes.",
            "output": [
                "Are mannose-binding lectin gene , MBL2 , polymorphisms associated with susceptibility to invasive pneumococcal disease in children?"
            ]
        },
        {
            "id": "task847-4a0990ba51e542f6b788307d49e89a83",
            "input": "To identify molecular features associated with clinico-pathological parameters in renal cell cancer.', 'Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging was employed for a kidney cancer tissue microarray containing tissue samples from 789 patients for which clinical follow-up data were available.', 'A comparison of mass spectrometric signals with clinico-pathological features revealed significant differences between papillary and clear cell renal cell cancer. Within the subgroup of clear cell RCC, statistical associations with tumor stage (seven signals, p<0.01 each), Fuhrman grade (seven signals, p<0.0001 each), and presence of lymph node metastases (10 signals, p<0.01 each) were found. In addition, the presence of one signal was significantly linked to shortened patient survival (p=0.0198).",
            "output": [
                "Does mALDI imaging on tissue microarrays identify molecular features associated with renal cell cancer phenotype?"
            ]
        },
        {
            "id": "task847-75c029e0aa5b4b2fa02d7104e0041d75",
            "input": "Formyl peptide receptor 1 (FPR1) as a regulator of innate inflammatory response has been implicated in tumor progression of gliomas. The purpose of the present study was to evaluate the prognostic significance and the ligand-receptor interaction of FPR1 in gastric cancer (GC).', 'FPR1 was immunohistochemically-analyzed in tissue sections originating from 116 GC patients. Reverse transcription-polymerase chain reaction (RT-PCR) was used for the assessment of interaction between FPR1 and the FPR1 ligand annexin A1 (AnxA1) in GC cells.', 'High FPR1 expression was significantly associated with stage IV disease, submucosal invasion, serosal invasion, and clinical outcome of GC. Multivariate analysis showed that high FPR1 expression was an independent risk factor of poor overall survival in GC patients. FPR1 expression increased significantly when AnxA1 overexpression was present in GC cells. A positive feedback regulation of FPR1 was involved in the AnxA1-FPR1 signal transduction.",
            "output": [
                "Is formyl Peptide receptor 1 expression associated with tumor progression and survival in gastric cancer?"
            ]
        },
        {
            "id": "task847-071cb17d45ad4d2a949f1bbab5dbe309",
            "input": "The scope of this work was to study synergism between human papillomavirus (HPV) infection and tobacco in vitro, both known to be independent risk factors for oral cancer.', 'HPV-positive and HPV-negative oral keratinocytes and oral HPV-negative fibroblasts were exposed to smokeless tobacco extract (STE) prepared from the Scandinavian (STE1) and US-type (STE2) snuff. Cell cycle profiles were determined with flow cytometry, and HPV E6/E7 mRNA expression in HPV-positive cells was assayed using RT-qPCR.', 'The exposure of HPV-positive keratinocytes with STE2 increased the number of aneuploid cells from 27% to 80% of which 44% were in S-phase, while none of the diploid cells were in S-phase. The changes after STE1 exposure were less than seen after STE2: from 27% to 31% of which 34% were in S-phase. STE had no effect on HPV16 E6/E7 expression in HPV-positive keratinocytes. In oral spontaneously transformed, HPV-negative keratinocytes, the number of aneuploid cells at G2-M stage increased after STE1 and STE2 exposure from 3% to 9% and 7%, respectively. In HPV-negative oral fibroblasts, the number of cells at G2-M phase increased from 11% to 21% after STE1 and 29% after STE2 exposure.",
            "output": [
                "Does smokeless tobacco increase aneuploidy in oral HPV16 E6/E7-transformed keratinocytes in vitro?"
            ]
        },
        {
            "id": "task847-a8b98dd6c1fb40aabd395f7cef340947",
            "input": "To evaluate whether and how the transcription factor early growth response gene 1 (EGR1) affects the osteogenic differentiation of dental stem cells.', 'Dental stem cells from apical papilla (SCAPs) and from the dental follicle (DFCs) were transfected with EGR1-specific siRNA or EGR-1 expression plasmid. Gene regulation was verified at protein level by Western blotting. The expression of the transcription factors distal-less homeobox 3 (DLX3), alkaline phosphatase (ALP) and bone morphogenetic protein 2 (BMP2), which are all regulators and markers of the osteogenic differentiation in dental stem cells, was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). To investigate mineralization, SCAP long-term cultures were stained with alizarin red after EGR1 over-expression.', 'EGR1 was induced in SCAPs during osteogenic differentiation. DLX3 and bone morphogenetic protein 2 (BMP2) were up-regulated after EGR1 over-expression and down-regulated after EGR1 depletion. The expression of ALP was also down-regulated after EGR1 depletion. The over-expression of EGR1 in SCAPs promoted mineralization after osteogenic differentiation.",
            "output": [
                "Does eGR1 support the osteogenic differentiation of dental stem cells?"
            ]
        },
        {
            "id": "task847-caef4d9881e747799f914e15b64064b8",
            "input": "The purpose of this study was to compare the in vivo anti-tumor efficacy of a mucoadhesive, lipid-based, oral paclitaxel formulation (DHP107) with traditional, intraperitoneal (IP) paclitaxel using an orthotopic mouse model of chemotherapy-sensitive SKOV3ip1 ovarian cancer.', 'To determine the optimal therapeutic dose of oral paclitaxel, DHP107 was administered per os to female athymic nude mice at 0, 25, or 50 mg/kg twice per week. Control mice received 100 \u00b5L saline once per week. IP injections of paclitaxel at 5 mg/kg once per week were used for comparison. To evaluate the potential therapeutic effect of metronomic DHP107 chemotherapy, mice received DHP107 50 mg/kg once per week per os, which was compared with 25 mg/kg twice per week and with vehicle-treated controls.', 'Low-dose DHP107 (25 mg/kg) twice per week was as effective as IP paclitaxel (5 mg/kg once a week) but high-dose DHP107 (50 mg/kg once per week) was less effective at inhibiting tumor growth in an orthotopic mouse model (88%, 82%, and 36% decrease in tumor weight, respectively). Mice that received 25 mg/kg DHP107 twice per week or 50 mg/kg DHP107 once per week per os had a significant decrease in tumor weight compared with vehicle-treated controls (p<0.01, both doses).",
            "output": [
                "Does metronomic oral paclitaxel show anti-tumor effects in an orthotopic mouse model of ovarian cancer?"
            ]
        },
        {
            "id": "task847-c00829be1c564c32b6102008545b6f47",
            "input": "It is known that noxious stimuli from inflamed tissue may increase the excitability of spinal dorsal horn neurons (a process known as central sensitization), which can signal back and contribute to peripheral inflammation. However, the underlying mechanisms have yet to be fully defined. A number of recent studies have indicated that spinal NF-\u03baB/p65 is involved in central sensitization, as well as pain-related behavior. Thus, the aim of this study was to determine whether NF-\u03baB/p65 can facilitate a peripheral inflammatory response in rat adjuvant-induced arthritis (AIA).', \"Lentiviral vectors encoding short hairpin RNAs that target NF-\u03baB/p65 (LV-shNF-\u03baB/p65) were constructed for gene silencing. The spines of rats with AIA were injected with LV-shNF-\u03baB/p65 on day 3 or day 10 after treatment with Freund's complete adjuvant (CFA). During an observation period of 20 days, pain-related behavior, paw swelling, and joint histopathologic changes were evaluated. Moreover, the expression levels of spinal tumor necrosis factor \u03b1 (TNF\u03b1), interleukin-1\u03b2 (IL-1\u03b2), and cyclooxygenase 2 (COX-2) were assessed on day 14 after CFA treatment.\", 'The presence of peripheral inflammation in rats with AIA induced an increase in NF-\u03baB/p65 expression in the spinal cord, mainly in the dorsal horn neurons and astrocytes. Delivery of LV-shNF-\u03baB/p65 to the spinal cord knocked down the expression of NF-\u03baB/p65 and significantly attenuated hyperalgesia, paw edema, and joint destruction. In addition, spinal delivery of LV-shNF-\u03baB/p65 reduced the overexpression of spinal TNF\u03b1, IL-1\u03b2, and COX-2.",
            "output": [
                "Does activation of spinal NF-\u03baB/p65 contribute to peripheral inflammation and hyperalgesia in rat adjuvant-induced arthritis?"
            ]
        },
        {
            "id": "task847-c3f6633ca3e14a4fab3577e280d7078e",
            "input": "Myeloperoxidase (MPO) is implicated as a local mediator of tissue damage when released extracellularly in many chronic inflammatory diseases. The purpose of this study was to explore the role of endogenous MPO in experimental rheumatoid arthritis (RA).', 'K/BxN serum-transfer arthritis was induced in C57BL/6 wild-type (WT) and MPO knockout (MPO(-/-) ) mice, and disease development was assessed. MPO activity was measured in joint tissues from mice with or without K/BxN arthritis. Collagen-induced arthritis (CIA) was induced in WT and MPO(-/-) mice, and disease development and immune responses were examined. MPO expression was assessed in synovial biopsy samples from patients with active RA, and the effect of MPO on synovial fibroblasts was tested in vitro.', 'MPO was up-regulated in the joints of mice with K/BxN arthritis, and MPO deficiency attenuated the severity of the disease without affecting circulating cytokine levels. In CIA, MPO(-/-) mice had enhanced CD4+ T cell responses and reduced frequency of regulatory T cells in the lymph nodes and spleen, as well as augmented interleukin-17A and diminished interferon-\u03b3 secretion by collagen-stimulated splenocytes, without an effect on circulating anticollagen antibody levels. Despite enhanced adaptive immunity in secondary lymphoid organs, CIA development was attenuated in MPO(-/-) mice. Intracellular and extracellular MPO was detected in the synovium of patients with active RA, and human MPO enhanced the proliferation and decreased the apoptosis of synovial fibroblasts in vitro.",
            "output": [
                "Is endogenous myeloperoxidase a mediator of joint inflammation and damage in experimental arthritis?"
            ]
        },
        {
            "id": "task847-8ec92e4c9f0749769a48a827b930bbc0",
            "input": "Rebamipide, a gastroprotective agent, has the ability to scavenge reactive oxygen radicals. Increased oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to investigate the impact of rebamipide on the development of arthritis and the pathophysiologic mechanisms by which rebamipide attenuates arthritis severity in a murine model of RA.', 'Collagen-induced arthritis (CIA) was induced in DBA/1J mice. Anti-type II collagen antibody titers and interleukin-17 (IL-17) levels were determined using enzyme-linked immunosorbent assay. The expression of transcription factors was analyzed by immunostaining and Western blotting. Frequencies of IL-17-producing CD4+ T cells (Th17 cells) and CD4+CD25+FoxP3+ Treg cells were analyzed by flow cytometry.', 'Rebamipide reduced the clinical arthritis score and severity of histologic inflammation and cartilage destruction in a dose-dependent manner. The joints isolated from rebamipide-treated mice with CIA showed decreased expression of nitrotyrosine, an oxidative stress marker. Rebamipide-treated mice showed lower circulating levels of type II collagen-specific IgG, IgG1, and IgG2a. Whereas the number of Th17 cells in spleens was decreased in rebamipide-treated mice with CIA, a significant increase in the number of Treg cells in spleens was observed. In vitro, rebamipide inhibited Th17 cell differentiation through STAT-3/retinoic acid receptor-related orphan nuclear receptor \u03b3t and reciprocally induced Treg cell differentiation through FoxP3. Rebamipide increased Nrf2 nuclear activities in murine CD4+ T cells and LBRM-33 murine T lymphoma cells. Heme oxygenase 1 (HO-1) expression in the spleens was markedly increased in rebamipide-treated mice.",
            "output": [
                "Does rebamipide suppress collagen-induced arthritis through reciprocal regulation of th17/treg cell differentiation and heme oxygenase 1 induction?"
            ]
        },
        {
            "id": "task847-9c7d4a10dd8a48ec8ac64b7f190fa0eb",
            "input": "Long noncoding RNAs (lncRNAs) play crucial regulatory roles in diverse biologic processes, but knowledge of lncRNAs in osteoarthritis (OA) is limited. The aim of this study was to identify lncRNA expression in articular cartilage and to explore the function of cartilage injury-related lncRNAs (lncRNA-CIR) in OA.', 'To identify lncRNAs specifically expressed in OA cartilage, we compared the expression of lncRNAs in OA cartilage with that in normal cartilage using microarray and quantitative polymerase chain reaction (qPCR) analyses. In OA cartilage, lncRNA-CIR was specifically, differentially, and highly expressed. The function of lncRNA-CIR was determined by silencing and overexpression in vitro. Extracellular matrix (ECM)-related molecules were detected by qPCR, Western blot, and immunofluorescence analyses.', 'Up to 152 lncRNAs were found to be differentially expressed (>8-fold) in OA and normal cartilage (82 lncRNAs more highly expressed and 70 less highly expressed in OA cartilage than in normal cartilage). A specific differentially expressed lncRNA-CIR was selected according to the results of the higher expression in OA cartilage and OA chondrocytes. The expression of lncRNA-CIR increased in chondrocytes with in vitro treatment with interleukin-1\u03b2 and tumor necrosis factor \u03b1. Silencing of lncRNA-CIR by small interfering RNA promoted the formation of collagen and aggrecan and reduced the expression of matrix-degrading enzymes, such as MMP13 and ADAMTS5. The expression of collagen and aggrecan was reduced, whereas the expression of matrix-degrading enzymes was increased, after overexpression of lncRNA-CIR.",
            "output": [
                "Does long noncoding RNA related to cartilage injury promote chondrocyte extracellular matrix degradation in osteoarthritis?"
            ]
        },
        {
            "id": "task847-dccec17282484f39b1dd831d61465416",
            "input": "Sleep disorders are common in patients with HIV/AIDS, and can lead to poor quality of life. Although many studies have investigated the aetiology of these disorders, it is still unclear whether impaired sleep quality is associated with HIV itself, social problems, or side effects of antiretroviral therapy (ART). Moreover, despite its known neurological associations, little is known about the role of the trans-activator of transcription (Tat) protein in sleep disorders in patients with HIV/AIDS. The purpose of this study was to test the hypothesis that the sleep quality of patients with HIV/AIDS affected by an altered circadian rhythm correlates with cerebrospinal HIV Tat protein concentration.', 'Ninety-six patients with HIV/AIDS between 20 and 69 years old completed the Pittsburgh Sleep Quality Index. Their circadian rhythm parameters of blood pressure, Tat concentration in cerebrospinal fluid, melatonin concentration, CD4 cell count and HIV RNA viral load in serum were measured.', 'The circadian amplitude of systolic blood pressure and the score for sleep quality (Pittsburgh Sleep Quality Index) were negatively correlated with HIV Tat protein concentration, while the melatonin value was positively correlated with Tat protein concentration.",
            "output": [
                "Does hIV Tat protein affect circadian rhythmicity by interfering with the circadian system?"
            ]
        },
        {
            "id": "task847-10625ffda9764bc88318a252dcc1dcce",
            "input": "Adolescent patients with chronic health conditions must gradually assume responsibility for their health. Self-management skills are needed for a successful transfer from adolescent to adult health care, but the development of these skills could be resource intensive. Pediatric providers are already instrumental in teaching patients about their health and may improve these skills. The aim of the study was to evaluate whether informal education of pediatric providers regarding transition improves inflammatory bowel disease (IBD) patient self-management skills.', 'Consecutive patients with IBD older than 10 years who presented to the outpatient setting were administered a survey regarding self-management behaviors in 2008 and 2011. During this time, several conferences on transition were presented to the providers.', 'In 2008, 294 patients completed the survey (82%) compared with 121 patients (89%) in 2011. The patient groups were comparable with respect to sex (boys 50% vs 42%), mean age (16.7 vs 16.2 years), and type of IBD (Crohn 68% vs 66%). The 13- to 15-year-olds reported calling in refills (11%, 8%, respectively), scheduling clinic appointment (0, 1%), preparing questions (13%, 5%), and taking the main role in talking during clinic visits (15%, 24%). The 16- to 18-year-olds reported calling in refills (13%, 27%), scheduling clinic appointments (9%, 6%), preparing questions (9%, 16%), and taking the main role in talking in clinic visits (36%, 45%). Responsibility for behaviors gradually increases with age, but did not differ significantly between 2008 and 2011.",
            "output": [
                "Does provider awareness alone improve transition readiness skills in adolescent patients with inflammatory bowel disease?"
            ]
        },
        {
            "id": "task847-51df481355cb406fa3f95425eea25a3e",
            "input": "Few studies investigated the best method for removing stains from different types of resin-based composite restorations and compared them to the more recently introduced nanocomposites. This study compared the effect of four methods for stain removal from composite resins; finishing with Sof-lex disks, using pumice and brush, bleaching with 10% carbamide peroxide and 38% hydrogen peroxide.', 'Twenty disk specimens were prepared. Specimens were immersed in a staining solution for 3\\xa0weeks. The stained surfaces of five specimens from each RBC material were treated with one of the treatment procedures. Colorimetric measurements were taken using spectrophotometer prior to and after staining, and then repeated after surface treatments. Color difference values were calculated.', \"One-way ANOVA indicated significant differences in color change of the three composite resin materials following staining. Filtek Z250 showed the least susceptibility to discoloration followed by Renamel, Filtek Supreme was the material most prone to discoloration. Two-way ANOVA and Tukey's Post Hoc showed that all stain removing procedures except polishing with pumice, were able to return Filtek Z250 to clinically acceptable color difference. While bleaching with 38% carbamide peroxide was not effective with Renamel. Only pumice and 10% carbamide peroxide were able to return Renamel to clinically acceptable color difference.",
            "output": [
                "Do the effectiveness of four methods for stain removal from direct resin-based composite restorative materials?"
            ]
        },
        {
            "id": "task847-37326a6e0a45475e9cc48ab14a1f4523",
            "input": "T-wave alternans (TWA) is an indicator of vulnerability to ventricular arrhythmias and is useful for predicting sudden cardiac death (SCD) in patients with various structural heart diseases. We evaluated whether high levels of time-domain TWA on ambulatory ECG (AECG) are associated with a history of ventricular fibrillation (VF) in Brugada syndrome (BrS) patients.', 'We examined the associations among VF history, family history of SCD, spontaneous type 1 electrocardiogram (ECG), late potentials, VF induction by programmed electrical stimulation, and TWA in 45 BrS patients (44 males; mean age, 45 \u00b1 15 years). TWA analyzed from 24-h AECG recordings using the modified moving average method was positive in 13 of 43 patients (30%). Patients with a history of VF had a significantly higher incidence of a positive TWA test (82% vs. 13%; P < 0.001) and spontaneous type 1 ECG (92% vs. 38%; P = 0.007) than those without VF history. Multivariate analysis indicated that positive TWA (OR 7.217; 95% CI 2.503-35.504; P = 0.002) and spontaneous type 1 ECG (OR 5.530; 95% CI 1.651-34.337; P = 0.020) were closely associated with VF history. Spontaneous type 1 ECG had high sensitivity (92%) but low specificity (63%). Positive TWA was a reliable marker with high sensitivity and specificity (82% and 88%, respectively).",
            "output": [
                "Is time-domain T-wave alternans strongly associated with a history of ventricular fibrillation in patients with Brugada syndrome?"
            ]
        },
        {
            "id": "task847-908e37591f744692a16c2e1d8102774d",
            "input": "The beta and gamma absorbed fractions in organs and tissues are the important key factors of radionuclide internal dosimetry based on Medical Internal Radiation Dose (MIRD) approach.', 'The aim of this study is to find suitable analytical functions for beta and gamma absorbed fractions in spherical and ellipsoidal volumes with a uniform distribution of iodine-131 radionuclide.', 'MCNPX code has been used to calculate the energy absorption from beta and gamma rays of iodine-131 uniformly distributed inside different ellipsoids and spheres, and then the absorbed fractions have been evaluated.', 'We have found the fit parameters of a suitable analytical function for the beta absorbed fraction, depending on a generalized radius for ellipsoid based on the radius of sphere, and a linear fit function for the gamma absorbed fraction.",
            "output": [
                "Does analytical function for beta and gamma absorbed fractions of iodine-131 in spherical and ellipsoidal volumes?"
            ]
        },
        {
            "id": "task847-f79aebb9a20741c39503f5962657713d",
            "input": "PARP-1 is important for the recognition of both endogenous and exogenous DNA damage, and binds to DNA strand breaks including intermediates of base excision repair (BER). Once DNA-bound, PARP-1 becomes catalytically activated synthesizing PAR polymers onto itself and other repair factors (PARylation). As a result, BER repair proteins such as XRCC1 and DNA polymerase \u03b2 (pol \u03b2) are more efficiently and rapidly recruited to sites of DNA damage. In the presence of an inhibitor of PARP activity (PARPi), PARP-1 binds to sites of DNA damage, but PARylation is prevented. BER enzyme recruitment is hindered, but binding of PARP-1 to DNA is stabilized, impeding DNA repair and leading to double-strand DNA breaks (DSB). Deficiencies in pol \u03b2(-/-) and Xrcc1(-/-) cells resulted in hypersensitivity to the PARP inhibitor 4-AN and reexpression of pol \u03b2 or XRCC1, in these contexts, reversed the 4-AN hypersensitivity phenotype. BER deficiencies also showed evidence of replication defects that lead to DSB-induced apoptosis upon PARPi treatment. Finally, the clinically relevant PARP inhibitors olaparib and veliparib also exhibited hypersensitivity in both pol \u03b2(-/-) and Xrcc1(-/-) BER-deficient cells. These results reveal heightened sensitivity to PARPi as a function of BER deficiency.",
            "output": [
                "Do base excision repair defects invoke hypersensitivity to PARP inhibition?"
            ]
        },
        {
            "id": "task847-116ca7d323134f8c8ea1a55b4411928b",
            "input": "This study evaluated risk factors for acute wheeze in preschool children and investigated whether subnormal levels of vitamin D were associated with increased risk for acute wheeze, atopy or viral/bacterial respiratory infections.', 'We recruited 130 children with acute wheeze, aged 6\\xa0months to 4\\xa0years, from paediatric emergency departments in Stockholm, Sweden, and 101 age-matched controls with no history of wheeze or sensitisation to airborne allergens. Parents answered standardised questionnaires, and blood samples were analysed for specific IgE to airborne and food allergens and levels of 25 hydroxyvitamin D (25(OH)D). Nasopharyngeal virus samples were collected during the emergency department visit in the group of children with wheeze, and a subset were also tested for bacteria.', 'Vitamin D insufficiency (25(OH)D\\xa0<\\xa075\\xa0nmol/L (30\\xa0ng/mL)) was associated with an odds ratio of 2.7 (95% confidence interval 1.1-6.2) for acute wheeze. However, no association was found between vitamin D insufficiency and atopy, presence of virus or bacteria or recurrent infections. Children older than 24\\xa0months were particularly at risk of subnormal vitamin D levels, irrespective of wheezing history.",
            "output": [
                "Are subnormal levels of vitamin D associated with acute wheeze in young children?"
            ]
        },
        {
            "id": "task847-6db5af4ff0bd4b148c40490fa36a10a1",
            "input": "Asthma guidelines recommend prescription of inhaled corticosteroids at a reduced dosage in children compared to older patients in order to minimize the systemic exposure and risk of unwanted side effects. In children, pressurized metered dose inhalers (pMDI) are recommended in combination with a valved holding chamber (VHC) to overcome the problem of coordinating inhalation with actuation. However, the influence of age and body size on the systemic exposure of drugs to be administered via a pMDI with VHC is still not fully elucidated. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed combination of beclometasone-dipropionate/formoterol-fumarate administered via pMDI with VHC in children, adolescents and adults.', 'The pharmacokinetics of formoterol and beclometasone-17-monopropionate (active metabolite of beclometasone-dipropionate) was evaluated over 8\\xa0h from three studies, each performed in a different age and body size group. Children (7-11 years, n\\xa0=\\xa020), adolescents (12-17 years, n\\xa0=\\xa029) and adults (\u226518 years, n\\xa0=\\xa024) received a single dose of beclometasone/formoterol (children: 200\\xa0\u03bcg/24\\xa0\u03bcg, adolescents and adults: 400\\xa0\u03bcg/24\\xa0\u03bcg) via pMDI with AeroChamber Plus\u2122.', 'The systemic exposure in children in comparison to adolescents was equivalent for formoterol while it was halved for beclometasone-17-monopropionate in accordance with the halved dose of beclometasone administered in children (90% CIs within 0.8-1.25 for formoterol and 0.4-0.625 for beclometasone-17-monopropionate). The systemic exposure to beclometasone-17-monopropionate and formoterol was equivalent between adolescents and adults.",
            "output": [
                "Is the systemic exposure to inhaled beclometasone/formoterol pMDI with valved holding chamber independent of age and body size?"
            ]
        },
        {
            "id": "task847-deadc6e4ff2840cdafab65fc2d6aff2e",
            "input": "Active transportation (AT) has been associated with positive health outcomes, yet limited research has addressed this with college students, a population at-risk for inactivity. The purpose of this study was to examine the relationship between AT behavior and objectively measured fitness outcomes.', 'A volunteer, convenience sample (n = 299) of college students from a large northeastern university completed a survey about their AT habits to and on campus and psychosocial constructs related to AT and participated in a laboratory-based fitness assessment (cardiovascular endurance, muscular strength and endurance, flexibility, body composition).Off-campus students were dichotomized as nonactive (0-1 AT trips/day) or active travelers (> 1 AT trips/day) to campus; t-tests compared nonactive and active travelers for psychosocial and fitness variables.', 'Students were 56.3% male, 79.2% non-Hispanic White, and primarily living off-campus (87%). Most students (n = 177, 59.2%) reported active travel between classes. Off-campus students were primarily active travelers (76.1%). Active travelers to campus had greater cardiovascular fitness (P = .005), were more flexible (P = .006) and had lower systolic blood pressure (P = .05) compared with nonactive travelers.",
            "output": [
                "Is active Transportation to and on Campus Associated With Objectively Measured Fitness Outcomes Among College Students?"
            ]
        },
        {
            "id": "task847-b0b57f95b2a14ca7806e853f6f7ffb41",
            "input": "Pseudomonas aeruginosa is an opportunistic pathogen with a high incidence of hospital infections that represents a threat to immune compromised patients. Genomic studies have shown that, in contrast to other pathogenic bacteria, clinical and environmental isolates do not show particular genomic differences. In addition, genetic variability of all the P. aeruginosa strains whose genomes have been sequenced is extremely low. This low genomic variability might be explained if clinical strains constitute a subpopulation of this bacterial species present in environments that are close to human populations, which preferentially produce virulence associated traits.', 'In this work, we sequenced the genomes and performed phenotypic descriptions for four non-human P. aeruginosa isolates collected from a plant, the ocean, a water-spring, and from dolphin stomach. We show that the four strains are phenotypically diverse and that this is not reflected in genomic variability, since their genomes are almost identical. Furthermore, we performed a detailed comparative genomic analysis of the four strains studied in this work with the thirteen previously reported P. aeruginosa genomes by means of describing their core and pan-genomes.",
            "output": [
                "Do pseudomonas aeruginosa clinical and environmental isolates constitute a single population with high phenotypic diversity?"
            ]
        },
        {
            "id": "task847-afab2739fdb34cfc8065cb480887ea11",
            "input": "Large copy number variations (CNV) can contribute to increased burden for neurodegenerative diseases. In this study, we analyzed the genome-wide burden of large CNVs > 100 kb in primary open angle glaucoma (POAG), a neurodegenerative disease of the eye that is the largest cause of irreversible blindness.', 'Genome-wide analysis of CNVs > 100 kb were analyzed in a total of 1720 individuals, including an Indian cohort (347 POAG cases and 345 controls) and a Caucasian cohort (624 cases and 404 controls). All the CNV data were obtained from experiments performed on Illumina 660W-Quad (infinium) arrays.', 'We observed that for both the populations CNVs > 1 Mb was significantly enriched for gene-rich regions unique to the POAG cases (P < 10(-11)). In the Indian cohort CNVs > 1 Mb (39 calls) in patients influenced 125 genes while in controls 31 such CNVs influenced only 5 genes with no overlap. In both cohorts we observed 1.9-fold gene enrichment in patients for deletions compared to duplications, while such a bias was not observed in controls (0.3-fold). Overall duplications > 1 Mb were more than deletions (Del/Dup = 0.82) confirming that the enrichment of gene-rich deletions in patients was associated with the disease. Of the 39 CNVs > 1 Mb from Indian patients, 28 (72%) also were implicated in other neurodegenerative disorders, like autism, schizophrenia, sensorineural hearing loss, and so forth. We found one large duplication encompassing CNTN4 gene in Indian and Caucasian POAG patients that was absent in the controls.",
            "output": [
                "Are gene-rich large deletions overrepresented in POAG patients of Indian and Caucasian origins?"
            ]
        },
        {
            "id": "task847-62448803e7894e78887dffc00623d253",
            "input": "To determine whether intratrigonal Onabotulinum toxin A (OnabotA) injection produces a different symptomatic outcome and duration of effect on ulcerative (Ulc) and nonulcerative (NUlc) bladder pain syndrome/interstitial cystitis (BPS/IC) patients and to compare the urinary levels of neurotrophines (NGF, BDNF, and GDNF) in response to OnabotA.', \"Ten Ulc and 14 NUlc bladder pain syndrome/interstitial cystitis patients were included in this study. OnabotA (100 U) was injected in 10 trigonal sites, each receiving 10 U in 1 mL of saline. Outcome measures included pain visual analog scale (0-10), a 3-day voiding chart, O'Leary-Sant Score (OSS), and quality of life (QoL) from International Prostate Symptoms Score assessed before treatment, 1 month after injection, and every 3 months afterwards. Urinary NGF, BDNF, and GDNF were accessed using ELISA, at same time points. Treatment duration was determined at the time patients requested another injection.\", 'Patients had a mean age of 40 \u00b1 12 years in the Ulc and 47 \u00b1 13 years in the NUlc group (ns). Mean values at baseline of pain intensity, frequency, nocturia, OSS, QoL, and urinary NGF, BDNF, GDNF were identical in the 2 groups. Patients with the Ulc phenotype had a longer duration of symptoms (28.8 \u00b1 11 vs 19.2 \u00b1 8 months, P = .018). Both groups responded equally to OnabotA, with significant improvements in pain intensity, frequency, nocturia, OSS, QoL, and urinary NGF, BDNF, GDNF. The effect lasted for 9 \u00b1 2.8 (Ulc) and 10.5 \u00b1 2 (NUlc) months.",
            "output": [
                "Do ulcerative and nonulcerative forms of bladder pain syndrome/interstitial cystitis differ in symptom intensity or response to onabotulinum toxin A?"
            ]
        },
        {
            "id": "task847-40984e3347cf4f8fa8fd92678e6e3f03",
            "input": "Different risk factors have been suggested for ischemic stroke in young adults. In a group of these patients despite of extensive diagnostic work-up, the primary cause remains unknown. Coagulation tendency is accounted as a possible cause in these patients. Previous studies on factor V Leiden (FVL) as the main cause of inherited thrombophilia for clarifying the role of FVL in stroke have resulted in controversial findings. The current study investigates the role of this factor in ischemic stroke among Iranians.', 'This case-control study was performed between September 2007 and December 2008 in Isfahan, Iran. The case group comprised of 22 patients of which 15 were males and 7 were females with age range of \u226450 years, diagnosed as ischemic stroke without classic risk factors and the control group consisted of 54 healthy young adults. After filling consent form, venous blood samples were obtained and sent to the laboratory for genetic examination.', 'No FVL mutation was found in the case group. There was one carrier of the mutation as heterozygous in the control group (relative frequency = 1.85%).",
            "output": [
                "Does factor V Leiden have a role in cryptogenic ischemic stroke among Iranian young adults?"
            ]
        },
        {
            "id": "task847-c9a43f19b7534706aba00277b5623944",
            "input": "We aimed to evaluate the relationship between estimated glomerular filtration rate (eGFR) and QT dispersion (QTd) in patients with coronary artery disease (CAD).', 'Sixty patients(mean age 62.72 \u00b1 12.48 years) included 46 male, (mean age 60.89 \u00b1 12.70 years)and 14 female (mean age 68.71\u00b1 9.86 years) were enrolled in this study. Patients were divided into 2 groups according to their eGFR using the 6 variable MDRD equation. Group 1 consisted of patients with estimated eGFR<60 ml/min/1.73m(2) and Group 2 consisted of patients witheGFR \u2265 60 ml/min/1.73m(2).', 'Baseline patient characteristics were homogeneous in both groups except for age, gender and smoking.Also, the extent of CAD was similar in both groups (p > 0.05) QTd values were found higher in group 1 than those of group 2 (57.23 \u00b1 40.65 ms vs. 31.23 \u00b1 14.47 ms, p = 0.002). After adjustment for age, gender and smoking using one-way ANCOVA test, statistically significant difference in QTd still existedbetween the groups (p=0.038).",
            "output": [
                "Does qT dispersion increase with low glomerular filtration rate in patients with coronary artery disease?"
            ]
        },
        {
            "id": "task847-9aeae32fdff74cdb9c79babcfed2e1bf",
            "input": "The development of reliable gene expression profiling technology increasingly impacts our understanding of lung cancer biology. Here, we used RNA sequencing (RNA-Seq) to compare the transcriptomes of non-small cell lung cancer (NSCLC) and normal lung tissues and to investigate expression in lung cancer tissues.', 'We enrolled 88 male patients (mean age, 61.2 years) with NSCLC. RNA-Seq was performed on 88 pairs of NSCLC tumor tissue and non-tumor tissue from 54 patients with adenocarcinoma and 34 patients with squamous cell carcinoma. Immunohistochemistry was performed to validate differential candidate gene expression in a different NSCLC group.', 'RNA-Seq produced 25.41 \u00d7 10(6) (\u00b1 8.90 \u00d7 10(6)) reads in NSCLC tissues and 24.70\u00d710(6) (\u00b1 4.70 \u00d7 10(6)) reads in normal lung tissues [mean (\u00b1 standard deviation)]. Among the genes expressed in both tissues, 335 were upregulated and 728 were downregulated \u2265 2-fold (p < 0.001). Four upregulated genes - CBX3, GJB2, CRABP2, and DSP - not previously reported in lung cancer were studied further. Their altered expression was verified by immunohistochemistry in a different set of NSCLC tissues (n = 154). CBX3 was positive in 90.3% (139 cases) of the samples; GJB2, in 22.7% (35 cases); CRABP2, in 72.1% (111 cases); and DSP, in 17.5% (27 cases). The positive rate of CRABP2 was higher in adenocarcinoma than squamous cell carcinoma (p < 0.01).",
            "output": [
                "Does rNA sequencing identify novel markers of non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-d038582b11a94309a4f022c71bfbd53a",
            "input": "Hepatic encephalopathy (HE) is associated with motor symptoms and attentional deficits, which are related to pathologically slowed oscillatory brain activity. Here, potential alterations of oscillatory activity in the somatosensory system were investigated.', '21 patients with liver cirrhosis and varying HE severity and 7 control subjects received electrical stimulation of the right median nerve while brain activity was recorded using magnetoencephalography (MEG). Oscillatory activity within the contralateral primary somatosensory cortex (S1) and its stimulus-induced modulation were analyzed as a function of disease severity.', 'Median nerve stimuli evoked an early broadband power increase followed by suppression and then rebound of S1 alpha and beta activity. Increasing HE severity as quantified by the critical flicker frequency (CFF) was associated with a slowing of the alpha peak frequency and a delay of the alpha rebound.",
            "output": [
                "Is hepatic encephalopathy associated with slowed and delayed stimulus-associated somatosensory alpha activity?"
            ]
        },
        {
            "id": "task847-abc9755ad51841a3ac5edf3c502b1791",
            "input": "Mitochondrion is considered as the major source of intracellular reactive oxygen species (ROS). H2S has been reported to be an antioxidant, but its mechanism remains largely elusive. P66Shc is an upstream activator of mitochondrial redox signaling. The aim of this study was to explore whether the antioxidant effect of H2S is mediated by p66Shc.', 'Application of exogenous H2S with its donor, NaHS, or overexpression of its generating enzyme, cystathionine \u03b2-synthase, induced sulfhydration of p66Shc, but inhibited its phosphorylation caused by H2O2/D-galactose in SH-SY5Y cells or in the mice cortex. H2S also decreased mitochondrial ROS production and protected neuronal cells against stress-induced senescence. PKC\u03b2II and PP2A are the two key proteins to regulate p66Shc phosphorylation. Although H2S failed to affect the activities of these two proteins, it disrupted their association. Cysteine-59 resides in proximity to serine-36, the phosphorylation site of p66Shc. The C59S mutant attenuated the above-described biological function of H2S.', 'We revealed a novel mechanism for the antioxidant effect of H2S and its role in oxidative stress-related diseases.",
            "output": [
                "Does sulfhydration of p66Shc at cysteine59 mediate the antioxidant effect of hydrogen sulfide?"
            ]
        },
        {
            "id": "task847-c113948e6a194f808bd0372279d00076",
            "input": "Since the initial reports of human epidermal growth factor receptor 2 (HER-2) expression as being prognostic in osteosarcoma, numerous small studies varying in the interpretation of the immunohistochemical (IHC) staining patterns have produced conflicting results. The Children's Oncology Group therefore embarked on a prospective biology study in a larger sample of patients to define in osteosarcoma the prognostic value of HER-2 expression using the methodology employed in the initial North American study describing an association between HER-2 expression and outcome.\", \"The analytic patient population was comprised of 149 patients with newly diagnosed osteosarcoma, 135 with localized disease and 14 with metastatic disease, all of whom had follow up clinical data. Paraffin embedded material from the diagnostic biopsy was stained with CB11 antibody and scored by two independent observers. Correlation of HER-2 IHC score and demographic variables was analyzed using a Fisher's exact test and correlation with survival using a Kaplan-Meier analysis.\", 'No association was found with HER-2 status and any of the demographic variables tested including the presence or absence of metastatic disease at diagnosis. No association was found between HER-2 status and either event free survival or overall survival in the patients with localized disease.",
            "output": [
                "Is hER-2 expression prognostic in osteosarcoma ; a Children 's Oncology Group prospective biology study?"
            ]
        },
        {
            "id": "task847-10bfb81cca524691a3fc873e47cee8f6",
            "input": "Shaoyao decoction (SYD) is a traditional Chinese medicine prescription formulated by Liu Wan-Su, a master of traditional Chinese medicine in Jin-Yuan Dynasty. SYD is effective in treating ulcerative colitis. Paeonol, a component of SYD, inhibits colorectal cancer (CRC) cell proliferation and induces CRC cell apoptosis. In this study, azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated CRC (caCRC) model and CRC cell lines were used to examine the effects of SYD on CRC in vivo and in vitro.', 'A translational medicine strategy based on phytomics quality control was adopted. Liquid chromatography was employed for the chemical characterization and chemical fingerprinting of SYD. Protein expression and macrophage existence were determined by immunohistochemistry and western blot. Serum cytokines were quantified by Luminex assay.', 'AOM/DSS-induced caCRC phenotypically resembled human caCRC. SYD significantly increased the survival rate of the mice, ameliorated the general well-being of the mice, and reduced the incidence and multiplicity of colonic neoplasms. SYD inhibited epithelial-mesenchymal transition (EMT), as indicated by upregulated epithelia cadherin and downregulated neuronal cadherin, fibronectin, vimentin, and transcription factor Snail. SYD reduced the expression levels of serum interleukin 1\u03b2, interleukin-6, tumor necrosis factor \u03b1, tumor-associated macrophages, and p65. These results showed that SYD can attenuate proinflammatory cytokines and inhibit EMT.",
            "output": [
                "Does shaoYao decoction ameliorate colitis-associated colorectal cancer by downregulating proinflammatory cytokines and promoting epithelial-mesenchymal transition?"
            ]
        },
        {
            "id": "task847-ec5b14306e934b3dabe443cae9bbc78d",
            "input": "Increased placental growth secondary to reduced apoptosis may contribute to the development of macrosomia in GDM pregnancies. We hypothesize that reduced apoptosis in GDM placentas is caused by dysregulation of apoptosis related genes from death receptors or mitochondrial pathway or both to enhance placental growth in GDM pregnancies.', 'Newborn and placental weights from women with no pregnancy complications (controls; N=5), or with GDM (N=5) were recorded. Placental villi from both groups were either fixed for TUNEL assay, or snap frozen for gene expression analysis by apoptosis PCR microarrays and qPCR.', 'Maternal, placental and newborn weights were significantly higher in the GDM group vs. Controls. Apoptotic index of placentas from the GDM group was markedly lower than the Controls. At a significant threshold of 1.5, seven genes (BCL10, BIRC6, BIRC7, CASP5, CASP8P2, CFLAR, and FAS) were down regulated, and 13 genes (BCL2, BCL2L1, BCL2L11, CASP4, DAPK1, I\u03baB\u03baE, MCL1, NF\u03baBIZ, NOD1, PEA15, TNF, TNFRSF25, and XIAP) were unregulated in the GDM placentas. qPCR confirmed the consistency of the PCR microarray. Using Western blotting we found significantly decreased placental pro-apoptotic FAS receptor and FAS ligand (FASL), and increased mitochondrial anti-apoptotic BCL2 post GDM insult. Notably, caspase-3, which plays a central role in the execution-phase of apoptosis, and its substrate poly (ADP-ribose) polymerase (PARP) were significantly down regulated in GDM placentas, as compared to non-diabetic Control placentas.",
            "output": [
                "Does gestational diabetes mellitus alter apoptotic and inflammatory gene expression of trophobasts from human term placenta?"
            ]
        },
        {
            "id": "task847-c8228e076e83464eb3109f993ffc7fbe",
            "input": "Pharmacological activation of the adaptive response to hypoxia is a therapeutic strategy of growing interest for neurological conditions, including stroke, Huntington's disease, and Parkinson's disease. We screened a drug library with known safety in humans using a hippocampal neuroblast line expressing a reporter of hypoxia-inducible factor (HIF)-dependent transcription.\", 'Our screen identified more than 40 compounds with the ability to induce hypoxia response element-driven luciferase activity as well or better than deferoxamine, a canonical activator of hypoxic adaptation. Among the chemical entities identified, the antihelminthic benzimidazoles represented one pharmacophore that appeared multiple times in our screen. Secondary assays confirmed that antihelminthics stabilized the transcriptional activator HIF-1\u03b1 and induced expression of a known HIF target gene, p21(cip1/waf1), in post-mitotic cortical neurons. The on-target effect of these agents in stimulating hypoxic signaling was binding to free tubulin. Moreover, antihelminthic benzimidazoles also abrogated oxidative stress-induced death in vitro, and this on-target effect also involves binding to free tubulin.",
            "output": [
                "Are antihelminthic benzimidazoles novel HIF activators that prevent oxidative neuronal death via binding to tubulin?"
            ]
        },
        {
            "id": "task847-73aa9b1d214649b8b213ebb858a366fe",
            "input": "Given the emerging role of microRNA in tumor disease progression, we investigated the association between microRNA expression, liver metastasis and prognosis of colorectal cancer.', 'Colorectal cancer tissues from patients with or without liver metastases were profiled to identify differentially expressed microRNA. Expression profile was further assessed using quantitative reverse transcription PCR and in situ hybridization. Correlation between miR-181a expression, the most differentially expressed microRNA, between patients with and without liver metastasis, and its downstream target genes were investigated using qRT-PCR. Luciferase reporter assay was conducted to establish functional association between miR-181a and its target genes. Manipulation of miR-181a expression and its consequences in tumor growth and metastasis were demonstrated in various in vitro and in vivo models.', 'miR-181a was revealed being the most elevated in CRC with liver metastases. miR-181a expression correlated with advanced stage, distant metastasis, and served as an independent prognostic factor of poor overall survival. Stable transfection of CRC cell lines with miR-181a promoted cell motility and invasion, as well as tumor growth and liver metastasis,while silencing its expression resulted in reduced migration and invasion. Additionally, we identified WIF-1 as direct and functional targets of miR-181a. Ectopic expression of miR-181a suppressed the epithelial markers E-cadherin and \u03b2-catenin, while enhanced the mesenchymal markers vimentin.",
            "output": [
                "Does microRNA-181a promote tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1?"
            ]
        },
        {
            "id": "task847-94917fe0ce9049b3a8a75707c0950d4c",
            "input": "Adolescent substance use has been associated with poorer neuropsychological functioning, but it is unclear if deficits predate or follow the onset of use. The goal of this prospective study was to understand how neuropsychological functioning during early adolescence could predict substance use by late adolescence.', \"At baseline, participants were 175 substance-use-na\u00efve healthy 12- to 14-year-olds (41% female) recruited from local schools. Participants completed extensive interviews and neuropsychological tests. Each year, participants' substance use was assessed. By late adolescence (ages 17 to 18), 105 participants transitioned into substance use and 75 remained substance-na\u00efve. Hierarchical linear regressions examined how baseline cognitive performance predicted subsequent substance use, controlling for common substance use risk factors (i.e., family history, externalizing behaviors, gender, pubertal development, and age).\", 'Poorer baseline performance on tests of cognitive inhibition-interference predicted higher follow-up peak drinks on an occasion (\u03b2 = -.15; p < .001), more days of drinking (\u03b2 = -.15; p < .001), and more marijuana use days (\u03b2 = -.17; p < .001) by ages 17 to 18, above and beyond covariates. Performances on short-term memory, sustained attention, verbal learning and memory, visuospatial functioning, and spatial planning did not predict subsequent substance involvement (ps > .05).",
            "output": [
                "Does inhibition during early adolescence predict alcohol and marijuana use by late adolescence?"
            ]
        },
        {
            "id": "task847-c68abbe4a42c4a999c1d8fb1f254cfe6",
            "input": "MicroRNA-26b (miR-26b) has been reported to be down-regulated in a wide range of malignant tumors, However, the mechanism by which miR-26b is implicated in breast cancer tumorigenesis is incompletely understood. This study was undertaken to evaluate the expression pattern of miR-26b and characterize its biological role in human breast cancer.', 'Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the expression levels of miR-26b in breast cancer and adjacent non-cancerous breast tissues. MTT, colony formation assay and cell cycle assay were carried out to characterize the miR-26b function. Finally, to validate the target gene of miR-26b, luciferase reporter assay was employed, followed by RT-PCR and Western blot confirmation.', \"Here, we found that miR-26b expression was relatively downregulated in breast cancer specimens (P<0.01). Overexpression of miR-26b dramatically suppressed cell proliferation, colony formation and induced G0/G1 cell cycle arrest of MDA-MB-231 and Mcf-7 cells. Luciferase assays revealed that miR-26b directly targeted the 3'UTR of CDK8. Overexpression of miR-26b led to the downregulation of CDK8 and \u03b2-catenin expression. Similarly, CDK8 knockdown by siRNA suppressed cell growth and subsequent \u03b2-catenin expression.",
            "output": [
                "Does miRNA-26b inhibit cellular proliferation by targeting CDK8 in breast cancer?"
            ]
        },
        {
            "id": "task847-abbe87e0cb5d4eb08a6015efdc50c1d6",
            "input": "To investigate localization and distribution of integrin subunit \u03b21, \u03b22 and \u03b23 and morphological changes of ligand-recepter binding in thrombi of acute pulmonary embolism (PE) patients and explore activation of circulated immune cells, inflammatory immune adherence and coagulation response in acute venous thrombosis.', 'Thrombi were collected from patients with acute PE. Immunohistochemistry was done to detect the expression and distribution of integrin \u03b21, \u03b22 and \u03b23 in cells within thrombi, and ligands of integrin subunit \u03b21, \u03b22 and \u03b23 were also determined by immunohistochemistry within the thrombi.', '1) Acute venous thrombi were red thrombi composed of skeletons and filamentous mesh containing large amounts of red blood cells and white blood cells; 2) Integrin subunit \u03b21, \u03b22 and \u03b23 were expressed on lymphocytes, neutrophils and platelets; 3) No expression of integrin \u03b21 ligands: Laminin, Fibronectin, Collagen I or Collagen-II on lymphocytes; integrin \u03b22 ligands including ICAM, factor X and iC3b are distributed on neutrophils, and ligand fibrinogen bound to neutrophils; integrin \u03b23 was expressed on platelets which form the skeleton of thrombi and bound to fibrinogen to construct mesh structure; 4) Factor Xa was expressed on the filamentous mesh; 5) Filamentous mesh was fully filled with red blood cell dominant blood cells.",
            "output": [
                "Are activation of circulated immune cells and inflammatory immune adherence involved in the whole process of acute venous thrombosis?"
            ]
        },
        {
            "id": "task847-7de1e0c956874dc1b934568f6b51d810",
            "input": "Acute pain can lead to immune dysfunction, which can be partly ameliorated by successful pain management. Opioids, which are widely used for analgesia, can result in the deterioration of immune function. This study aimed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery.', '60 patients undergoing gastric cancer surgery were equally randomized into two groups. They received post-operative patient-controlled intravenous (IV) analgesia using morphine either with or without flurbiprofen. Visual analogue scale (VAS) scores, Bruggemann comfort scale (BCS) scores, morphine consumption, time of first flatus, incidence of nausea/vomiting, and T-lymphocyte subsets (CD3\u207a, CD4\u207a, and CD8\u207a) and natural killer cells (CD3\u207bCD16\u207aCD56\u207a) were evaluated.', 'No significant difference was observed in the VAS scores, BCS scores, and nausea/vomiting incidence between groups. Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone. The expression of CD3\u207a, CD4\u207a, CD4\u207a/CD8\u207a, and CD3\u207bCD16\u207aCD56\u207a decreased at 2 hours after incision and, except for CD3\u207bCD16\u207aCD56\u207a, returned to baseline at 120 hours after surgery. Moreover, the expression of CD3\u207bCD16\u207aCD56\u207a at 2 hours after incision and the expression of CD3\u207a, CD4\u207a, CD4\u207a/CD8\u207a, and CD3\u207bCD16\u207aCD56\u207a at 24 hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone.",
            "output": [
                "Does flurbiprofen improve dysfunction of T-lymphocyte subsets and natural killer cells in cancer patients receiving post-operative morphine analgesia?"
            ]
        },
        {
            "id": "task847-5d231308a82747b89352e622663cbde1",
            "input": "Intermittent hypoxia (IH)-induced activation of pro-inflammatory pathways is a major contributing factor to the cardiovascular pathophysiology associated with obstructive sleep apnea (OSA). Obesity is commonly associated with OSA although it remains unknown whether adipose tissue is a major source of inflammatory mediators in response to IH. The aim of this study was to test the hypothesis that IH leads to augmented inflammatory responses in human adipocytes when compared to cells of non-adipocyte lineages.', 'Human primary subcutaneous and visceral adipocytes, human primary microvascular pulmonary endothelial cells (HUMEC-L) and human primary small airway epithelial cells (SAEC) were exposed to 0, 6 or 12 cycles of IH or stimulated with tumor necrosis factor (TNF)-\u03b1. IH led to a robust increase in NF-\u03baB DNA-binding activity in adipocytes compared with normoxic controls regardless of whether the source of adipocytes was visceral or subcutaneous. Notably, the NF-\u03baB response of adipocytes to both IH and TNF-\u03b1 was significantly greater than that in HUMEC-L and SAEC. Western blotting confirmed enhanced nuclear translocation of p65 in adipocytes in response to IH, accompanied by phosphorylation of I-\u03baB. Parallel to p65 activation, we observed a significant increase in secretion of the adipokines interleukin (IL)-8, IL-6 and TNF-\u03b1 with IH in adipocytes accompanied by significant upregulation of mRNA expression. PCR-array suggested profound influence of IH on pro-inflammatory gene expression in adipocytes.",
            "output": [
                "Are human adipocytes highly sensitive to intermittent hypoxia induced NF-kappaB activity and subsequent inflammatory gene expression?"
            ]
        },
        {
            "id": "task847-3e4f0b2808bd49ea9e1476901e99f7d9",
            "input": "Previous research demonstrating that specific performance outcome goals can be achieved in different ways is functionally significant for springboard divers whose performance environment can vary extensively. This body of work raises questions about the traditional approach of balking (terminating the takeoff) by elite divers aiming to perform only identical, invariant movement patterns during practice.', 'A 12-week training program (2 times per day; 6.5 hr per day) was implemented with 4 elite female springboard divers to encourage them to adapt movement patterns under variable takeoff conditions and complete intended dives, rather than balk.', \"Intraindividual analyses revealed small increases in variability in the board-work component of each diver's pretraining and posttraining program reverse-dive takeoffs. No topological differences were observed between movement patterns of dives completed pretraining and posttraining. Differences were noted in the amount of movement variability under different training conditions (evidenced by higher normalized root mean square error indexes posttraining). An increase in the number of completed dives (from 78.91%-86.84% to 95.59%-99.29%) and a decrease in the frequency of balked takeoffs (from 13.16%-19.41% to 0.63%-4.41%) showed that the elite athletes were able to adapt their behaviors during the training program. These findings coincided with greater consistency in the divers' performance during practice as scored by qualified judges.",
            "output": [
                "Does increasing functional variability in the preparatory phase of the takeoff improve elite springboard diving performance?"
            ]
        },
        {
            "id": "task847-e37632db498a47989d4cfd9d42e75f9d",
            "input": "This analysis examines whether or not younger caregivers, parents of children with developmental disabilities, differed from controls in terms of cytomegalovirus (CMV) seropositivity and CMV-specific antibody titre. Secondly, it examined whether any particular socio-demographics, health behaviours, or psychological/caregiving variables were associated with a higher CMV antibody titre among caregivers.', 'Young caregivers and age- and sex-matched controls were compared with respect to their reported health behaviour and psychosocial status as well as latent virus control.', 'One hundred and seventeen parents of children with developmental disabilities and 52 control parents completed standard measures of health behaviours, socio-demographics, perceived stress, depression and anxiety, caregiver burden, child problem behaviours. They also provided a blood sample assayed for the presence of CMV-specific antibody.', 'Caregivers were no more likely to be CMV positive than controls and did not have higher antibody titres against CMV. In addition, there was no association between CMV antibody titre in seropositive caregivers and any of the psychological/caregiving variables. However, higher CMV antibody titres were significantly associated with a higher BMI, lower exercise levels, smoking, and lower fruit and vegetable and fat intake among seropositive caregivers.",
            "output": [
                "Are anticytomegalovirus antibody titres associated with caregiving burden in younger caregivers?"
            ]
        },
        {
            "id": "task847-ee4f9ca382244a4c85c5930c7d021a7b",
            "input": "Sleep disorders are associated with cardiovascular complications and preterm delivery (PTD). Insufficient sleep results in metabolic alterations and increased inflammation, both known to contribute to placental abruption (abruption), a determinant of PTD. We examined associations of abruption with sleep duration and complaints of vital exhaustion.', 'The study included 164 abruption cases and 160 controls in a multicenter study in Peru. Data on habitual sleep duration and vital exhaustion during the first 6 months of pregnancy were elicited during interviews conducted following delivery. Women were categorized according to short, normal and long sleep duration (\u22646, 7-8 and \u22659\\u2009h); and frequency of feeling exhausted. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.', 'Short and long sleep durations were associated with increased odds of abruption. The ORs of abruption in relation to short (\u22646\\u2009h) and long (\u22659\\u2009h) sleep duration were 2.0 (95% CI 1.1-3.7) and 2.1 (95% CI 1.1-4.1), compared with normal sleep duration (7-8\\u2009h). Complaints of vital exhaustion were also associated with abruption (OR\\u2009=\\u20092.37; 95% CI 1.46-3.85), and were independent of sleep duration.",
            "output": [
                "Is maternal sleep duration and complaints of vital exhaustion during pregnancy associated with placental abruption?"
            ]
        },
        {
            "id": "task847-2d5416dbcb3c4d99a0b9dc0d394e12d0",
            "input": "The aim of this study is to determine the consequences of delayed presentation of anorectal malformations and emphasize the causes of delayed diagnosis of these malformations.', 'We retrospectively reviewed 54 neonatal patients with a diagnosis of anorectal malformations. Group 1 consisted of 35 patients diagnosed within the first 48\\u2009h of life and Group 2 included 19 patients diagnosed after 48\\u2009h of life.', 'Obstructive symptoms at the time of diagnosis, overall complications and the mean postoperative hospitalization period in Group 2 were markedly higher than that of Group 1. A comprehensive neonatal examination within the first 48\\u2009h of life was performed in 32 (91.4%) patients in Group 1 and 5 (26.3%) of the patients in Group 2 (p\\u2009<\\u20090.001).",
            "output": [
                "Is the passage of meconium alone a sign of correctly positioned anus?"
            ]
        },
        {
            "id": "task847-212b44e97d4340e3ab8f750c6300d8ca",
            "input": "Coagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined.', '60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Patients were categorized in two groups according to sepsis severity and organ failure and MODS development was assessed in the first 48 h from ICU admission. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and endothelial cell specific molecule-1(endocan) levels, as well as procalcitonin (PCT) and C-reactive protein (CRP) were determined within the first 24h of the onset of the disease. Predictive APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores were calculated on the day of ICU admission. Data were used to determine an association between day 1 biomarker levels, organ dysfunction score values and the development of organ failure, multiple organ dysfunction syndrome (MODS), and mortality during 28 days. These connections were determined by plotting of receiver operating characteristic (ROC) curves. Differences between groups were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test.', 'Concentration of endocan was significantly higher in the group of patients with sepsis induced organ failure, MODS development and in the group of non- survivors in contrast to group with less severe form of the disease, without multiorgan failure, and in contrast to group of survivors (p<0.05). Values of areas under the ROC curves showed that endocan levels had good discriminative power for more severe course of sepsis, MODS development and possible discriminative power for mortality prediction (AUC: 0.81, 0.67, 0.71 retrospectively), better than PCT for fatality (AUC:053) and better than APACHE II (AUC:0.55) and SOFA (AUC: 0.57) scores for organ failure.",
            "output": [
                "Is endocan useful biomarker of survival and severity in sepsis?"
            ]
        },
        {
            "id": "task847-e058c9b0e57144198db3552fb5ba0d3e",
            "input": "Hepatocyte nuclear factor 4\u03b1 (HNF4\u03b1) is a liver enriched transcription factor and is indispensable for liver development. However, the role of HNF4\u03b1 in hepatocellular carcinoma (HCC) progression remains to be elucidated. We report that reduced HNF4\u03b1 expression correlated well with the aggressive clinicopathological characteristics of HCC and predicted poor prognosis of patients. HNF4\u03b1 levels were even lower in metastatic HCCs, and ectopic HNF4\u03b1 expression suppressed the metastasis of hepatoma cells both in vitro and in vivo. Forced HNF4\u03b1 expression attenuated the expression and nuclear translocation of RelA (p65) and impaired NF-\u03baB activation through an IKK-independent mechanism. Blockage of RelA robustly attenuated the suppressive effect of HNF4\u03b1 on hepatoma cell metastasis. MicroRNA (miR)-7 and miR-124 were transcriptionally up-regulated by HNF4\u03b1, which repressed RelA expression by way of interaction with RelA-3' untranslated region (UTR). In addition, nuclear factor kappa B (NF-\u03baB) up-regulated the expression of miR-21 in hepatoma cells, resulting in decreased HNF4\u03b1 levels through down-regulating HNF4\u03b1-3'UTR activity.",
            "output": [
                "Does hepatocyte nuclear factor 4\u03b1-nuclear factor-\u03baB feedback circuit modulate liver cancer progression?"
            ]
        },
        {
            "id": "task847-657c1f2ad81a4d72975ebcbd469c783c",
            "input": "To investigate the possibility of using a modified reverse transfer function (RTF) measurement intraoperatively during surgery of a new transcutaneous bone conduction hearing implant to evaluate the status of the device.', 'Tests were performed on a cadaver skull (preclinically) and two conductive hearing loss patients implanted with a new transcutaneous bone conduction implant. During intraoperative activation, the RTF was measured using a microphone attached perpendicularly and directly to the skin in the middle section of the forehead.', 'The RTF could be measured for all frequencies from 500 to 6, 000 Hz.",
            "output": [
                "Do intraoperative measurement for a new transcutaneous bone conduction hearing implant?"
            ]
        },
        {
            "id": "task847-4669fe35bd8d46b199e1a7180f67773e",
            "input": "To observe the effects of Sanhuangyinchi decoction (SHYCD) pretreatment on acute hepatic failure (AHF) induced by D-galactosamine and lipopolysaccharide (LPS) in rats and explore the possible mechanisms involving antioxidant stress and cell apoptosis-related protein expression.', 'Forty-eight SD rats were randomized equally into control group, AHF model group, high-, medium- and low-dose SHYCD groups, and Bicyclol group. Five days after administration of the corresponding drugs, the rats were challenged with peritoneal D-galactosamine (700 mg/kg) plus LPS (10 ug/kg) injections to induce AHF acute hepatic failure except for those in the control group. At 48 h after the injections, blood samples were collected from the rats to detect the levels of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver were examined; immunohistochemistry and western blotting were used to detect caspase-3 protein expression in the liver.', 'The levels of ALT, AST, TBIL, TP and INR in the 3 SHYCD groups and Bicyclol group significantly decreased (P<0.05) while FIB significantly increased in comparison with those in the model group. SHYCD obviously ameliorated the pathological changes, enhanced SOD activity (P<0.05), and decreased MDA levels (P<0.05) and caspase-3 expression (P<0.05) in the liver tissue. SHYCD at the medium dose produced similar effects to Bicyclol (P>0.05) and showed better effects at the high dose than Bicyclol (P<0.05).",
            "output": [
                "Does [ Sanhuangyinchi decoction pretreatment ameliorate acute hepatic failure in rats by suppressing antioxidant stress and caspase-3 expression ]?"
            ]
        },
        {
            "id": "task847-a9110bcf0abf41239930123e9e78ee9c",
            "input": "To investigate the effect of 1,25-dihydroxyvitamin D3 (1,25VD3) on house dust mites (HDM)-induced expression of thymic stromal lymphopoietin (TSLP) in human airway epithelial cells in vitro.', 'Human airway epithelial 16HBE cells were incubated with 200, 400, and 800 U/L in the absence or presence of 1,25VD3 (10(-8) mol/L) for 6 h and 24 h, and TSLP mRNA and protein expressions in the cells were assessed using quantitative PCR and ELISA.', '16HBE cells incubated with HDM at 200, 400, and 800 U/L showed significantly increased TSLP mRNA and protein expressions (P<0.05). Pretreatment of the cells with 1,25VD3 obviously lowered 400 U/L HDM-induced TSLP expressions (P<0.05), but 1,25VD3 added along with HDM in the cells did not produce significant effects on TSLP expressions (P=0.58).",
            "output": [
                "Does [ 1,25-dihydroxyvitamin D3 pretreatment inhibit house dust mite-induced thymic stromal lymphopoietin release by human airway epithelial cells ]?"
            ]
        },
        {
            "id": "task847-ae09d6852e6a4fb695962f631ba47125",
            "input": "To explore the role of SCF/c-Kit signaling in the invasion of bladder cancer T24 cells.', 'Western blotting was used to detect the expression of c-Kit and PI3K pathway activation stimulated by stem cell factor (SCF) in T24 cells. The invasiveness of T24 cells before and after SCF stimulation and Wortmannin (aspecific PI3K inhibitor) treatment was evaluated using Transwell invasion assay (direct and indirect counting methods).', 'T24 cells expressed c-Kit protein and showed obvious Akt phosphorylation after stimulation with SCF (1 ng/ml) for 24 h. Compared to the control group, SCF stimulation (1 ng/ml) caused a greater number of T24 cells to migrate through the polycarbonate film (P<0.01), and this effect was blocked by the application of Wortmannin before the stimulation.",
            "output": [
                "Does [ SCF/c-Kit signaling promote invasion of T24 cells via PI3K pathway ]?"
            ]
        },
        {
            "id": "task847-66ee3a8e52d641a29b385f3fa24bae2d",
            "input": "This study is in an attempt to evaluate the diagnostic significance to predict the spermatogenesis of azoospermic men in examination of serum follicle-stimulating hormone (FSH) combination with serum inhibin B (INHB).', 'Quantitative examination of serum FSH and INHB was performed in 95 case of azoospermic men. According to their classifications of testicular biopsy with histopathological examination, there were 20 patients of Sertoli cell only, 25 of hypospermatogenesis, 18 of spermatogenic maturation arrest (complete or incomplete), and 32 of normal spermatogenesis. The association of serum FSH and INHB levels with histopathological classifications were analyzed by using statistical software.', 'Serum FSH, INHB and INHB/FSH levels of Sertoli cell only differed with statistical significance from hypospermatogenesis, spermatogenic maturation arrest and normal spermatogenesis (P<0.05). FSH, in which there were no statistical significance among the latter three classifications (P>0.05). Serum FSH, INHB and INHB/FSH levels were no relationship with maturation arrest (P>0.05), but were negatively related to the other classifications (P<0.05). INHB level less than 28.55 pg/ml predicted Sertoli cell only in a sensitivity of 97% and a specificity of 85%.",
            "output": [
                "Does [ Serum follicle-stimulating hormone in combination with serum inhibin B evaluate spermatogenesis of azoospermic men ]?"
            ]
        },
        {
            "id": "task847-971eddcedf6b43b4a1033f980f6ba9b0",
            "input": "Nagashima-type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma (PPK). Very recently, putative loss-of-function mutations in SERPINB7, which encodes a member of the serine protease inhibitor superfamily and is abundantly expressed in the epidermis, have been identified as a cause of NPPK.', 'To confirm further the role of SERPINB7 mutations in the pathogenesis of NPPK.', 'We analysed 10 Japanese families with NPPK using Sanger and/or whole-exome sequencing.', 'We identified one novel and three recurrent null mutations in SERPINB7. In all the families, the NPPK trait was inherited in an autosomal recessive manner; in one of the families, there was pseudodominant inheritance, which had not been described in NPPK.",
            "output": [
                "Does highly prevalent SERPINB7 founder mutation cause pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis?"
            ]
        },
        {
            "id": "task847-79b25b51863947388d5b09a654ed36a0",
            "input": "Clinical trials have shown promising results with the use of subcallosal cingulate gyrus deep brain stimulation (DBS) for treatment-resistant depression. However, strategies to manage patients who do not respond to this therapy have not been explored in detail. In rats, DBS in the ventromedial prefrontal cortex (vmPFC) induces a significant antidepressant-like response in the forced swim test (FST). We have used this test to investigate potential interactions between DBS and clinically used augmentative regimens.', 'Rats undergoing the FST were treated with vmPFC DBS along with different augmentative drugs, namely buspirone, risperidone and pindolol. Locomotor activity was tested in an open field.', 'DBS induced a significant reduction in immobility scores as compared to saline treated controls. These antidepressant-like effects, however, were not potentiated by the co-administration of buspirone, risperidone or pindolol.",
            "output": [
                "Do augmentative therapies potentiate the antidepressant-like effects of deep brain stimulation in rats?"
            ]
        },
        {
            "id": "task847-64199f77806b411e8b676aa7e9de6ee7",
            "input": "Obesity has shown a positive association with depression. We aimed to investigate the relationships among body weight, body mass index (BMI=kg/m(2)), change in a depression rating scale, and change in a functional scale with fluoxetine treatment for hospitalized patients with major depressive disorder (MDD).', 'A total of 131 acutely ill inpatients with MDD were enrolled to receive 20mg of fluoxetine daily for 6 weeks. The 17-item Hamilton Depression Rating Scale (HAMD-17) for symptom and the Work and Social Adjustment Scale (WSAS) for functioning were assessed at weeks 0, 1, 2, 3, 4, and 6. Remission was defined as a score of\u22647 on the HAMD-17 at endpoint. Body weight, body length, and BMI were measured at baseline. Pearson correlation coefficients (r) were calculated among body weight, BMI, HAMD-17 score change, and WSAS score change.', 'Of the 131 participants, 126 (96.2%) had at least one post-baseline assessment and were included in the analysis. Significant differences in body weight and BMI existed between remitters and nonremitters. There were statistically significant relationships among baseline body weight, baseline BMI, HAMD-17 score change, and WSAS score change at end point.",
            "output": [
                "Does both body weight and BMI predict improvement in symptom and functioning for patients with major depressive disorder?"
            ]
        },
        {
            "id": "task847-ff233eddd6eb4b4a8b0768fbf2971fd0",
            "input": "Nasopharyngeal carriage of Streptococcus pneumoniae is a prerequisite for invasive disease, but the majority of carriage episodes are asymptomatic and self-resolving. Interactions determining the development of carriage versus invasive disease are poorly understood but will influence the effectiveness of vaccines or therapeutics that disrupt nasal colonization.', 'We sought to elucidate immunological mechanisms underlying noninvasive pneumococcal nasopharyngeal carriage.', 'Pneumococcal interactions with human nasopharyngeal and bronchial fibroblasts and epithelial cells were investigated in vitro. A murine model of nasopharyngeal carriage and an experimental human pneumococcal challenge model were used to characterize immune responses in the airways during carriage.', 'We describe the previously unknown immunological basis of noninvasive carriage and highlight mechanisms whose perturbation may lead to invasive disease. We identify the induction of active transforming growth factor (TGF)-\u03b21 by S. pneumoniae in human host cells and highlight the key role for TGF-\u03b21 and T regulatory cells in the establishment and maintenance of nasopharyngeal carriage in mice and humans. We identify the ability of pneumococci to drive TGF-\u03b21 production from nasopharyngeal cells in vivo and show that an immune tolerance profile, characterized by elevated TGF-\u03b21 and high nasopharyngeal T regulatory cell numbers, is crucial for prolonged carriage of pneumococci. Blockade of TGF-\u03b21 signaling prevents prolonged carriage and leads to clearance of pneumococci from the nasopharynx.",
            "output": [
                "Is density and duration of pneumococcal carriage maintained by transforming growth factor \u03b21 and T regulatory cells?"
            ]
        },
        {
            "id": "task847-92d3d7761c604b2c86377fb4e10740d9",
            "input": "Chronic stress is generally known to exacerbate the development of numerous neuropsychiatric diseases such as fear and anxiety disorders, which is at least partially due to the disinhibition of amygdala subsequent to the prolonged stress exposure. GABA receptor A (GABAAR) mediates the primary component of inhibition in brain and its activation produces two forms of inhibition: the phasic and tonic inhibition. While both of them are critically engaged in limiting the activity of amygdala, their roles in the amygdala disinhibition subsequent to chronic stress exposure are largely unknown.', 'We investigated the possible alterations of phasic and tonic GABAAR currents and their roles in the amygdala disinhibition subsequent to chronic stress. We found that both chronic immobilization and unpredictable stress led to long lasting loss of tonic GABAAR currents in the projection neurons of lateral amygdala. By contrast, the phasic GABAAR currents, as measured by the spontaneous inhibitory postsynaptic currents, were virtually unaltered. The loss of tonic inhibition varied with the duration of daily stress and the total days of stress exposure. It was prevented by pretreatment with metyrapone to block corticosterone synthesis or RU 38486, a glucocorticoid receptor antagonist, suggesting the critical involvement of glucocorticoid receptor activation. Moreover, chronic treatment with corticosterone mimicked the effect of chronic stress and reduced the tonic inhibition in lateral amygdala of control mice. The loss of tonic inhibition resulted in the impaired GABAergic gating on neuronal excitability in amygdala, which was prevented by metyrapone pretreatment.",
            "output": [
                "Does chronic stress impair GABAergic control of amygdala through suppressing the tonic GABAA receptor currents?"
            ]
        },
        {
            "id": "task847-0c0b302865b445758f9fc2ec59379734",
            "input": "Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disturbance in which patients enact their dreams while in REM sleep. The behavior is typically violent in association with violent dream content, so serious harm can be done to the patient or the bed partner. The prevalence of RBD is well-known in Parkinson's disease, Lewy body dementia, and multiple systems atrophy. However, its prevalence and causes in stroke remained unclear. The aim of this study was to determine factors influencing the appearance of RBD in a prospective cohort of patients with acute ischemic stroke.\", 'A total of 2,024 patients with first-ever or recurrent acute ischemic stroke were admitted to the Acute Stroke Unit at the Prince of Wales Hospital between January 2010 and November 2011; 775 of them received an MRI scan. Within 2 days of admission, a research nurse collected demographic and clinical data and assessed the severity of each stroke using the National Institute of Health Stroke Scale (NIHSS). One hundred and nineteen of the 775 patients meeting study entry criteria formed the study sample. All eligible participants were invited to attend a research clinic 3 months after the onset of the index stroke. In the attendance, a research assistant administered the MMSE and the 13-item RBD questionnaire (RBDQ).', 'Among 119 stroke patients, 10.9% were exhibited RBD, defined as an REM sleep behavior disorder questionnaire score of 19 or above. The proportion of patients with acute brainstem infarct was significantly higher in RBD patients than those without RBD. Compared with patients without RBD, RBD patients were more likely to have brainstem infarcts and had smaller infarct volumes. In a multivariate analysis, in which stroke location and infarct volume were inserted, brainstem infarcts were an independent predictor of RBD (odds ratio\\u2009=\\u20093.686; P\\u2009=\\u20090.032).",
            "output": [
                "Do brainstem infarcts predict REM sleep behavior disorder in acute ischemic stroke?"
            ]
        },
        {
            "id": "task847-f867ee748d114fb3af636a5f04d599ba",
            "input": "The endosteum of the bone marrow provides a specialized hypoxic niche that may serve to preserve the integrity, pluripotency, longevity and stemness of resident mesenchymal stem cells (MSCs). To explore the molecular genetic consequences of such a niche we subjected human (h) MSCs to a pO2 of 4 mmHg and analyzed global gene expression and alternative splicing (AS) by genome-exon microarray and RT-qPCR, and phenotype by western blot and immunostaining.', 'Out of 446 genes differentially regulated by >2.5-fold, down-regulated genes outnumbered up-regulated genes by 243:203. Exon analyses revealed 60 hypoxia-regulated AS events with splice indices (SI) >1.0 from 53 genes and a correlation between high SI and degree of transcript regulation. Parallel analyses of a publicly available AS study on human umbilical vein endothelial cells (HUVECs) showed that there was a strong cell-specific component with only 11 genes commonly regulated in hMSCs and HUVECs and 17 common differentially spliced genes. Only 3 genes were differentially responsive to hypoxia at the gene (>2.0) and AS levels in both cell types. Functional assignments revealed unique profiles of gene expression with complex regulation of differentiation, extracellular matrix, intermediate filament and metabolic marker genes. Antioxidant genes, striated muscle genes and insulin/IGF-1 signaling intermediates were down-regulated. There was a coordinate induction of 9 out of 12 acidic keratins that along with other epithelial and cell adhesion markers implies a partial mesenchymal to epithelial transition.",
            "output": [
                "Does severe hypoxia exert parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells?"
            ]
        },
        {
            "id": "task847-65d7b8fcc3094924a5d496306c98e2c8",
            "input": "In the present study, we investigated the survival of patients who received postoperative renal replacement therapy (RRT) after cardiac surgery. We specifically focused on factors predicting long-term outcome in elderly patients.', 'Data of all patients that received unintentional renal replacement therapy following cardiac surgery between 2004 and 2010 were analyzed. Logistic- and Cox regression analyses were performed to detect the predictors of early and late mortality, respectively.', 'During the study period, 11,899 patients underwent cardiac surgery in our center. Post-operative RRT was performed in 138 patients (1.2%). In this group of patients, 30-day mortality included 72 patients (52%) and the total overall mortality included 107 patients (77.5%). Regression analyses revealed that age predicted 30-day mortality (odds ratio\\u2009=\\u20091.08 [1.03 to 1.12]) as well as late mortality (odds ratio\\u2009=\\u20091.05 [1.02 to 1.07].",
            "output": [
                "Does impact of postoperative renal replacement therapy on long-term outcome after cardiac surgery increase with age?"
            ]
        },
        {
            "id": "task847-c59e73548da84847839dbb07c3f56c6f",
            "input": "To evaluate the effects of a collaborative pharmacy benefits manager (PBM)/ health plan-administered drug therapy management (DTM) program on healthcare utilization and costs in patients with diabetes treated with polypharmacy.', 'Retrospective quasi-experimental design with comparison group.', 'This DTM program was a collaborative effort between the PBM, PerformRx, and the care management departments of Keystone First (KF) and AmeriHealth Caritas Pennsylvania (ACP) care management departments, targeting patients with diabetes using >15 medications. Pharmacists reviewed member profiles and made evidencebased prescriber and patient interventions, working directly with prescribers and indirectly with members, via care managers. Care managers provided additional services not otherwise within the scope of DTM. The study group consisted of 954 DTM participants reviewed by a pharmacist between November 1, 2010, and July 31, 2011. The control group consisted of 810 matched DTM participants not reviewed by a pharmacist.', 'Intervention acceptance rates for KF and ACP were 33% and 26%, respectively. The study group demonstrated lower inpatient admissions and emergency department utilization rates, although only the KF study group inpatient admission rate achieved statistical significance (76.4%; P = .0002). The study groups realized statistically significant total cost savings (pharmacy + medical) compared with their corresponding control groups (47.8% KF, P = .0039; 50.7% ACP, P = .0497) despite non-statistically significant increases in pharmacy costs.",
            "output": [
                "Does collaborative DTM reduce hospitalization and healthcare costs in patients with diabetes treated with polypharmacy?"
            ]
        },
        {
            "id": "task847-270e0f8d99a94556ac6ba816a4dc04df",
            "input": "Skeletal muscles that are under the influence of tetanus toxin show an exaggerated reflex response to stretch. We examined which changes in the stretch reflex may underlie the exaggerated response.', 'H-reflexes were obtained from the tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles in rats 7 days after intramuscular injection of tetanus toxin into the TA.', 'We found effects of the toxin on the threshold, amplitude, and duration of H-waves from the TA. The toxin inhibited rate-dependent depression in the FDB between the stimulation frequencies of 0.5\u201350 HZ and when a conditioning magnetic stimulus applied to the brain preceded a test electrical stimulus delivered to the plantar nerve.",
            "output": [
                "Does tetanus toxin reduce local and descending regulation of the H-reflex?"
            ]
        },
        {
            "id": "task847-02ccff81faa947df8f8747180d38b751",
            "input": "Arterial blood pressure (BP) is a reliable marker of circulatory dysfunction in cirrhotic patients. There are no prospective studies evaluating the association between different levels of arterial BP and ascites development in compensated cirrhotic patients. Therefore, we evaluated the relationship between arterial BP and ascites development in compensated cirrhotic patients.', 'A total of 402 patients with compensated HCV-related cirrhosis were prospectively followed during 6 years to identify ascites development. At baseline, patients underwent systolic, diastolic and mean arterial pressure (MAP) measurements. Any history of arterial hypertension was also recorded. The occurrence of events such as bleeding, hepatocellular carcinoma, death and liver transplantation prior to ascites development were considered as competing risk events.', 'Over a median of 156 weeks, ascites occurred in 54 patients (13%). At baseline, MAP was significantly lower in patients with ascites development (75.9 mm/Hg [95%CI, 70.3-84.3]) than those without ascites (93.6 mm/Hg [95% CI: 86.6-102.3]). After adjusting for covariates, the 6-year cumulative incidence of ascites was 40% (95%CI, 34%-48%) for patients with MAP<83.32 mm/Hg. In contrast, cumulative incidences of ascites were almost similar among patients with MAP values between 83.32 mm/Hg and 93.32 mm/Hg (7% [95% CI: 4%-12%]), between 93.32 mm/Hg and 100.31 mm/Hg (5% [95% CI: 4%-11%]) or higher than 100.31 mm/Hg (3% [95% CI: 1%-6%]). The MAP was an independent predictor of ascites development.",
            "output": [
                "Is arterial blood pressure closely related to ascites development in compensated HCV-related cirrhosis?"
            ]
        },
        {
            "id": "task847-acab9f4ae49544c69335c960688a0095",
            "input": "The EML4-ALK fusion gene is more frequently found in younger, never smoking patients with lung cancer. Meanwhile, never smokers exposed to secondhand tobacco smoke (SHS) during childhood are diagnosed at a younger age compared with never smoking patients with lung cancer who are not exposed. We, therefore, hypothesized that SHS, which can induce DNA damage, is associated with the EML4-ALK fusion gene.', 'We compared the frequency of the EML4-ALK fusion gene among 197 never smoker patients with lung cancer with and without a history of exposure to SHS during childhood at Mayo Clinic.', 'The EML4-ALK fusion gene was detected in 33% of cases from never smokers with a history of SHS exposure during childhood, whereas 47% of never smoking lung cancer cases without a history of childhood SHS exposure tested positive for the fusion gene.",
            "output": [
                "Is evidence that the lung Adenocarcinoma EML4-ALK fusion gene caused by exposure to secondhand tobacco smoke during childhood?"
            ]
        },
        {
            "id": "task847-0a9a6705c476453d96e34becc3199c2c",
            "input": "Key molecules involved in microRNA (miRNA) biogenesis, such as DROSHA, XPO5, and DICER, have been identified in trophoblast cells, confirming that the miRNA biogenesis pathway is active in human placenta. In addition, miRNAs regulate uterine gene expression associated with inflammatory responses during the peri-implantation period and participate in maternal-fetal immune tolerance. The purpose of this study was to demonstrate whether genetic polymorphisms in miRNA machinery genes show an association with idiopathic recurrent pregnancy loss (RPL) in Korean women.', 'We performed a case-control study with 238 controls and 338 women who had experienced at least two consecutive pregnancy losses between 1999 and 2010. Genotypes of miRNA machinery genes, including DICER rs3742330, DROSHA rs10719, RAN GTPase (RAN) rs14035, and exportin-5 (XPO5) rs11077 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The logistic odds ratios (ORs) of RPL were estimated with a 95% confidence interval (CI) in multivariate analysis after maternal age adjustment. Gene-gene interactions among the loci of the four gene polymorphisms were evaluated using the multifactor dimensionality reduction (MDR) method.', 'The RAN rs14035 CC genotype and DICER rs3742330/DROSHA rs10719 GG/TC+CC, rs3742330/RAN rs14035 GG/CC, and DICER rs3742330/XPO5 rs11077 GG/AC+CC combinations were significantly associated with increased RPL risk, whereas the RAN rs14035 CT, DICER rs3742330/RAN rs14035 AA+AG/CT+TT, DROSHA rs10719/RAN rs14035 TC+CC/CT+TT, and RAN rs14035/XPO5 rs11077 CT+TT/AA combinations reduced RPL risk. The A-T-T-C and G-C-T-A allele combinations (DICER/DROSHA/RAN/XPO5) were 20 times more frequent in the RPL group than in the control group.",
            "output": [
                "Are genetic variants in microRNA machinery genes associated [ corrected ] with idiopathic recurrent pregnancy loss risk?"
            ]
        },
        {
            "id": "task847-5e45cc89f7f34c2d8f4289cd2ea21a6c",
            "input": "The rs1800255, COL3A1 2209\\xa0G>A polymorphism in the alpha 1 chain of collagen type III has been associated with an increased risk of pelvic organ prolapse (POP). In one of our previous studies however, polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) misdiagnosed rs1800255, COL3A1 2209\\xa0G>A in 6\\xa0% of cases. The high-resolution melting (HRM) analysis on the contrary obtained a 100\\xa0% accordance for this specific polymorphism and was used in the present study to validate this risk factor for POP.', 'In this case-control study, women with and without symptoms of POP were included and compared. DNA was extracted from blood samples. HRM analysis was used to assess for the presence of the homozygous rs1800255. Groups were compared using the Pearson chi-square, Mann-Whitney, and t tests. The discrepancy between HRM and PCR-RFLP results was investigated using PCR-RFLP results available from our previous study.', 'The study included 354 women: 272 patients with POP and 82 controls; 18 (7\\xa0%) cases versus 3 (4\\xa0%) controls had a homozygous rs1800255, COL3A1 2209\\xa0G>A polymorphism (odds ratio 1.9, 95\\xa0% confidence interval 0.5-6.9, compared to the wild type), and thus no association between POP and the homozygous polymorphism could be demonstrated. A discrepancy between HRM and PCR-RFLP results was found in 8\\xa0% of the samples.",
            "output": [
                "Is collagen type III alpha 1 polymorphism ( rs1800255 , COL3A1 2209 G > A ) assessed with high-resolution melting analysis associated with pelvic organ prolapse in the Dutch population?"
            ]
        },
        {
            "id": "task847-79f471154f0e47559f2b8effb58d381e",
            "input": "Cerebral malaria (CM) is associated with long-term neurocognitive impairment in children \u22655 years of age. No prospective studies to date have assessed neurocognitive impairment in children with CM <5 years of age, or in children with severe malarial anemia (SMA), a form of severe malaria estimated to affect as many as 5 million children annually.', \"Children <5 years of age presenting to Mulago Hospital, Kampala, Uganda, with CM (n = 80) or SMA (n = 86) were assessed for overall cognitive ability, attention, and associative memory 1 week after discharge and 6 and 12 months later. The z scores for each domain were computed based on scores of 61 healthy community children (CC), who were also tested at enrollment and 6 and 12 months later. Groups were compared using mixed linear models, adjusted for age, weight for age, and child's education.\", 'At 12 months, children with CM had lower adjusted scores than CC in cognitive ability (P < .001), attention (P = .02), and associative memory, (P = .002). Children with SMA had lower scores than CC in cognitive ability (P = .01) but not attention or associative memory. Cognitive ability scores in children with CM and SMA did not differ significantly.",
            "output": [
                "Is severe malarial anemia associated with long-term neurocognitive impairment?"
            ]
        },
        {
            "id": "task847-61f0c99f48a94c8fa01c768e18347721",
            "input": "Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence.\", 'We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session.', 'Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion.",
            "output": [
                "Do neural responses to exclusion predict susceptibility to social influence?"
            ]
        },
        {
            "id": "task847-8575aecde9a94f6ca4d9546f23c0866b",
            "input": "Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care.', 'From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture.', 'A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321).",
            "output": [
                "Is viral infection uncommon in adult patients with severe hospital-acquired pneumonia?"
            ]
        },
        {
            "id": "task847-b4f99f9cdc4c49fd955731cac897b500",
            "input": "The observed association between pioglitazone and bladder cancer could be causal or because of bias in the design of prior studies. We hypothesize that proteinuria testing may lead to detection bias if routine test results for proteinuria lead to a full urinalysis.', 'We reanalyzed patients with diabetes mellitus within Kaiser Permanente Northern California. Logistic and Cox regression adjusted for age, sex, race, and smoking were used to assess the association of proteinuria testing with pioglitazone use, subsequent full urinalysis, and diagnosis with bladder cancer.', 'Patients treated with pioglitazone were more likely than others with diabetes to undergo testing for proteinuria (p\\u2009<\\u20090.001). The odds of positive tests for proteinuria were higher among pioglitazone-treated patients (OR\\u2009=\\u20091.41, 95%CI 1.36-1.46). A positive proteinuria test was associated with increased odds of completing a urinalysis in the following 6\\u2009months (OR\\u2009=\\u20091.78, 95%CI 1.73-1.85). Negative and positive proteinuria test results were inversely (hazard ratio (HR) 0.63, 95%CI 0.52-0.75) and positively associated (HR 2.45, 95%CI 2.12-2.82) with bladder cancer risk, respectively. Adjustment for negative and positive proteinuria testing reduced the magnitude of association between pioglitazone and bladder cancer by only 5 to 10% (ever-exposed HR: from 1.06 to 1.01 and >4\\u2009years exposure HR: from 1.38 to 1.28).",
            "output": [
                "Is proteinuria testing among patients with diabetes mellitus associated with bladder cancer diagnosis : potential for unmeasured confounding in studies of pioglitazone and bladder cancer?"
            ]
        },
        {
            "id": "task847-01e9d4a4f7da43aca93c1e5839de2a01",
            "input": "The precise knowledge of anatomy and the region of transverse process (TP) and superior articular processes (AP) and their distance from the skin are important in blocking and treating lumbar facet syndrome. Evaluation of these anatomic distances from 3rd and 5th lumbar vertebrae in both sides and in different body mass index (BMI) in healthy volunteers might improve knowledge of ultrasound (US) lumbar medial branch nerve blocks (LMBB).', 'Bilateral US in the 3rd and 5th lumbar vertebrae of 64 volunteers carried out and the distance between skin to TP and skin to AP was measured. These distances were compared on both sides and in different BMI groups. The analysis was done using SPSS 11. Analysis of variance was used to compare the means at three vertebral levels (L3-L5) and different BMI groups. P values less than 0.05 were considered statistically significant. The paired t-test was used to compare the mean distance between skin to TP and skin to AP on both sides.', 'The distance between skin to TP and skin to AP of 3rd vertebrae to 5th vertebrae was increased in both right and left sides (P < 0.001) from up to down. The mean distance from skin to TP were greater on the left side compared to the right in all three vertebral levels from L3 to L5 (P values 0.014, 0.024, and 0.006 respectively). The mean distance from skin to TP and the skin to AP was statistically significant in different BMI groups (P < 0.001).",
            "output": [
                "Does survey of sonoanatomic distances for lumbar medial branch nerve block in healthy volunteers?"
            ]
        },
        {
            "id": "task847-0f6698908938416d942d25abec6d926d",
            "input": "Various parts of Margaritaria discoidea find use in traditional medicine in the treatment of pain and oedema. This study evaluated the anti-allergic, anti-inflammatory and anti-arthritic effects of a 70% (v/v) aqueous ethanol extract of the stem bark of Margaritaria discoidea, MDE in rodents.', \"Systemic anaphylaxis was induced by the injection of compound 48/80 into mice and their survival rate was monitored to evaluate the anti-allergic action of the extract. The effect of MDE assessed on the maximal and total oedema responses in the mouse carrageenan-induced paw oedema was used to evaluate the anti-inflammatory action of the extract while the Freund's adjuvant-induced arthritis model was employed to study the anti-arthritic effects of MDE.\", \"MDE dose-dependently increased the time for compound 48/80-induced mortality in mice. MDE suppressed the mean maximal swelling and the total paw swellings induced over 6 h in the carrageenan-induced paw oedema when administered either prophylactically or therapeutically. MDE caused a reduction in serum levels of TNF\u03b1 and IL-6 and significantly suppressed Freund's adjuvant-induced arthritis.",
            "output": [
                "Does margaritaria discoidea ( Euphorbiaceae ) stem bark extract attenuate allergy and Freund 's adjuvant-induced arthritis in rodents?"
            ]
        },
        {
            "id": "task847-cf617b993cf141e59f5468a9013c8a8b",
            "input": "Tumour cells alter the characteristics of the adjacent stroma to create a supportive microenvironment during cancer progression. In vitro and in vivo experiments were carried out to verify the role of stromal TGF-\u03b21 in reinforcing of the invasive potential in low invasive cancer.', 'Isolated NF or CAF was co-cultured with low invasive HSC-2 cells to evaluate whether stromal TGF-\u03b21 induced PDPN expression by Transwell invasion and influenced tumour growth in orthotopic xenografts.', 'Stimulation by TGF-\u03b21 promoted PDPN expression and Transwell invasion through SMAD signalling as well as activation of Src, P38 mitogen activated protein kinase and extracellular regulated kinase 1/2. PDPN induction was T\u03b2RII-dependent. Tumour growth of HSC-2 OSCC in a mouse xenograft was intensified in the tumour CAF microenvironment.",
            "output": [
                "Is stromal transforming growth factor-beta 1 crucial for reinforcing the invasive potential of low invasive cancer?"
            ]
        },
        {
            "id": "task847-34df869bb6464cc789ef061665523d79",
            "input": "To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models.', 'HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting.', 'The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL.",
            "output": [
                "Does eGF reverse multi-drug resistance via the p-ERK pathway in HepG2/ADM and SMMC7721/ADM hepatocellular carcinoma models?"
            ]
        },
        {
            "id": "task847-c17f11ba79f4453f8c0f76147c2f1f5f",
            "input": "The concept of ward culture has been proposed as a reason for the often reported differences in treatment decisions when managing inpatient aggression. We therefore studied whether staff on wards actually shares similar perceptions and attitudes about aggression and whether the specialty of the ward on which the staff members work influences these opinions.', \"The Attitudes Towards Aggression Scale was used to assess attitudes towards aggression in 31 closed psychiatric wards. Altogether 487 staff members working on the study wards were asked to fill in the scale. Respondent's gender, age, educational level, working experience on the current ward, and specialty of this ward (acute, forensic, rehabilitation) served as background variables.\", 'Most of the variance found was due to differences between individuals. Belonging to the personnel of a particular ward did not explain much of the variance.",
            "output": [
                "Does psychiatric staff on the wards share attitudes on aggression?"
            ]
        },
        {
            "id": "task847-90b79a7ea1f14f039d4dd36391b2040d",
            "input": "Arthritis and valvular carditis coexist in several human rheumatic diseases, including systemic lupus erythematosus, rheumatic fever, and rheumatoid arthritis. T cell receptor-transgenic K/BxN mice develop spontaneous autoantibody-associated arthritis and valvular carditis. The common Fc receptor \u03b3 (FcR\u03b3) signaling chain is required for carditis to develop in K/BxN mice. FcR\u03b3 pairs with numerous receptors in a variety of cells. The aim of this study was to identify the FcR\u03b3-associated receptors and Fc\u03b3 receptor (Fc\u03b3R)-expressing cells that mediate valvular carditis in this model.', 'We bred K/BxN mice lacking the genes that encode activating Fc\u03b3 receptors (Fc\u03b3RI, Fc\u03b3RIII, and Fc\u03b3RIV), and we assessed these mice for valvular carditis. We similarly evaluated complement component C3-deficient K/BxN mice. Immunohistochemistry, bone marrow transplantation, and macrophage depletion were used to define the key FcR\u03b3-expressing cell type.', 'Genetic deficiency of only one of the activating Fc\u03b3 receptors did not prevent carditis, whereas deficiency of all 3 activating Fc\u03b3 receptors did. Further analysis demonstrated that Fc\u03b3RIII and Fc\u03b3RIV were the key drivers of valve inflammation; Fc\u03b3RI was dispensable. C3 was not required. FcR\u03b3 expression by radioresistant cells was critical for valvular carditis to develop, and further analysis indicated that macrophages were the key candidate Fc\u03b3R-expressing effectors of carditis.",
            "output": [
                "Do fc\u03b3 receptor III and Fc\u03b3 receptor IV on macrophages drive autoimmune valvular carditis in mice?"
            ]
        },
        {
            "id": "task847-92a0df48ff1a4b64b7e5b7e6a0266e88",
            "input": "Physical therapists and occupational therapists practicing in acute care hospitals play a crucial role in discharge planning. A standardized assessment of patients' function could be useful for discharge recommendations.\", 'The study objective was to determine the accuracy of \"6-Clicks\" basic mobility and daily activity measures for predicting discharge from an acute care hospital to a home or institutional setting.', 'The study was retrospective and observational.', '\"6-Clicks\" scores obtained at initial visits by physical therapists or occupational therapists and patients\\' discharge destinations were used to develop and validate receiver operating characteristic curves for predicting discharge destination. Positive predictive values (PPV), negative predictive values (NPV), and likelihood ratios were calculated.', 'Areas under the receiver operating characteristic curves for basic mobility scores were 0.857 (95% confidence interval [CI]=0.852, 0.862) and 0.855 (95% CI=0.850, 0.860) in development and validation samples, respectively. Areas under the curves for daily activity scores were 0.846 (95% CI=0.841, 0.851) and 0.845 (95% CI=0.840, 0.850) in development and validation samples, respectively. Cutoff scores providing the best accuracy for determining discharge destination were 42.9 for basic mobility and 39.4 for daily activity. For basic mobility, the PPV was 0.748 and the NPV was 0.801 in both development and validation samples. For daily activity, the PPVs were 0.787 and 0.784 and the NPVs were 0.748 and 0.746 in development and validation samples, respectively.",
            "output": [
                "Do aM-PAC `` 6-Clicks '' functional assessment scores predict acute care hospital discharge destination?"
            ]
        },
        {
            "id": "task847-8b3721f28a3e4abda688ae761ba8c383",
            "input": "The objective of this study is to characterize differential proteomic expression among well-differentiation and poor-differentiation colorectal carcinoma tissues and normal mucous epithelium.', 'The study is based on quantitative 2-dimensional gel electrophoresis and analyzed by PDquest.', 'Excluding redundancies due to proteolysis and posttranslational modified isoforms of over 600 protein spots, 11 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Progression-associated proteins belong to the functional complexes of tumorigenesis, proliferation, differentiation, metabolism, and the regulation of major histocompatibility complex processing and other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in CRC. Among various differentiation stage of CRC tissues, we identified calreticulin precursor, MHC class I antigen (human leukocyte antigen A ), glutathione S-transferase pi1, keratin 8, heat shock protein 27, tubulin beta chain, triosephosphate, fatty acid-binding protein, hemoglobin (deoxy) mutant with val b 1 replaced by met (HBB), and zinc finger protein 312 (FEZF2).",
            "output": [
                "Does proteomic analysis reveal novel proteins associated with progression and differentiation of colorectal carcinoma?"
            ]
        },
        {
            "id": "task847-ebfd05baa45549f1b1d787ddce4461d8",
            "input": "This study examined the impact of omentin on myocardial injury in a mouse model of ischemia/reperfusion (I/R) and explored its underlying mechanisms.', 'Obesity is a major risk factor for ischemic heart disease. Omentin is a circulating adipokine that is down-regulated by obesity.', 'In patients who underwent successful reperfusion treatment after acute myocardial infarction, cardiac function and perfusion defect were assessed by using scintigraphic images. Mice were subjected to myocardial ischemia followed by reperfusion.', 'This study found that high levels of plasma omentin were associated with improvement of heart damage and function after reperfusion therapy in patients with acute myocardial infarction. Systemic administration of human omentin to mice led to a reduction in myocardial infarct size and apoptosis after I/R, which was accompanied by enhanced phosphorylation of AMP-activated protein kinase (AMPK) and Akt in the ischemic heart. Fat-specific overexpression of human omentin also resulted in reduction of infarct size after I/R. Blockade of AMPK or Akt activity reversed omentin-induced inhibition of myocardial ischemic damage and apoptosis in mice. In cultured cardiomyocytes, omentin suppressed hypoxia/reoxygenation-induced apoptosis, which was blocked by inactivation of AMPK or Akt.",
            "output": [
                "Does omentin prevent myocardial ischemic injury through AMP-activated protein kinase- and Akt-dependent mechanisms?"
            ]
        },
        {
            "id": "task847-1f5951cbee014559a8d66b040dcd495f",
            "input": "The purpose of this study was to determine if glycemic complexity, along with hypoglycemia and hyperglycemia, was associated with worse outcomes after cardiac surgery.', 'We conducted a retrospective analysis of 970 patients who had insulin infusions designed to keep blood glucose levels between 80 and 110 mg/dL. Glycemic complexity was calculated using jackknifed approximate entropy. Logistic regression was used to adjust for confounders.', 'A total of 495 patients (51%) developed complications, and 32 patients (3.3%) died. Along with older age, comorbidities, and complicated surgeries, any hypoglycemia (glucose<71 mg/dL) and the number of glucose values greater than 140 mg/dL were independent predictors of complications. Increased risk of mortality, after adjusting for other risk factors, was associated with older age, longer perfusion time, receiving intraoperative transfusions, and greater jackknifed approximate entropy of the glucose time series.",
            "output": [
                "Are hyperglycemia , hypoglycemia , and glycemic complexity associated with worse outcomes after surgery?"
            ]
        },
        {
            "id": "task847-6165395663ad48fc86d69fc9e00fb966",
            "input": "Intermountain Risk Score (IMRS) uses the admission complete blood count and basic metabolic profile to predict mortality. Intermountain Risk Score has been validated in medical patients but has not been evaluated in trauma. This study tested whether IMRS is predictive of mortality in a trauma population at a level I trauma center.', 'Admitted trauma patients with complete blood count and basic metabolic profile from October 2005 to December 2011 were evaluated. Thirty-day and 1-year IMRS were calculated using multivariable modeling. Mortality was determined using the medical record and Social Security Administration death data.', 'Three thousand six hundred thirty-seven females and 5901 males were evaluated. Intermountain Risk Score was highly predictive of death at 30 days (c-statistics, c = 0.772 for females; c = 0.783 males) and 1 year (c = 0.778 for females; c = 0.831 males). Cox regression analysis, adjusted for injury severity score, blunt vs penetrating, and length of stay, showed increased mortality risks among patients in the moderate- and high-risk IMRS-defined groups at both 30 days and 1 year, with hazard ratios ranging from 4.96 to 57.88 (all P < .001).",
            "output": [
                "Does the Intermountain Risk Score predict mortality in trauma patients?"
            ]
        },
        {
            "id": "task847-cd06281174aa462d877e22f7bbaeb9ae",
            "input": "Yes-associated protein (YAP) has been reported to be associated with the prognosis of various cancers and also to affect epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) activity in ovarian cancer cell lines. However, few studies have evaluated YAP protein expression in lung cancer, and the results have lacked consistency.', 'YAP expression was evaluated in a total of 205 curatively resected lung adenocarcinomas and 36 cases of EGFR-mutated TKI-treated patients. Correlations between the expression of YAP and clinicopathologic features, response to EGFR-TKI treatment, and prognostic significance were analyzed.', 'High cytoplasmic YAP expression was positively correlated with the clinicopathologic parameters that have been associated with favorable prognosis. Multivariate analysis revealed that high cytoplasmic YAP expression was an independent prognostic factor in lung adenocarcinomas (progression-free survival: hazard ratio [HR] 0.659; 95 % confidence interval [CI] 0.431-1.010; p = 0.050; overall survival: HR, 0.474; 95 % CI 0.263-0.854; p = 0.013) and EGFR-TKI-treated patients with EGFR mutation (progression-free survival: HR, 0.346; 95 % CI 0.146-0.818; p = 0.016; overall survival: HR, 0.291; 95 % CI 0.125-0.676; p = 0.004).",
            "output": [
                "Is cytoplasmic YAP expression associated with prolonged survival in patients with lung adenocarcinomas and epidermal growth factor receptor tyrosine kinase inhibitor treatment?"
            ]
        },
        {
            "id": "task847-dbb9c9fcb4e248c79b5e2073c49eb52f",
            "input": "Within pediatric diabetes management, two electronic measures of adherence exist: frequency of daily blood glucose monitoring (BGM) and the BOLUS score, a measure of frequency of mealtime insulin bolusing. Past research has demonstrated that the BOLUS score is superior to daily BGM in predicting youths' glycated hemoglobin (HbA1c) in a cross-sectional study. We present data comparing the two adherence measures in predicting HbA1c using a prospective, longitudinal design.\", \"Blood glucose meter data and insulin pump records were collected from a clinical database of 175 youths with type 1 diabetes (mean age, 11.7 \u00b1 3.6 years at baseline). Youths' HbA1c levels occurring at the download time and at 3, 6, 9, and 12 months post-downloads were also collected. We calculated youths' mean BGM and BOLUS score using a standardized protocol.\", \"Intraclass correlations (ICCs) revealed significant absolute equivalence between youths' predicted HbA1c values using BOLUS and BGM scores and future actual HbA1c values up to 12 months post-download. However, the ICCs of BOLUS scores with future HbA1c values were consistently higher than those of the BGM scores. Also, the predictions of the BOLUS scores were significantly more accurate (P \u2264 0.002) than those of the BGM scores based on the root mean squared error of predictions.",
            "output": [
                "Does frequency of mealtime insulin bolus predict glycated hemoglobin in youths with type 1 diabetes?"
            ]
        },
        {
            "id": "task847-c71b0b5f7cab4e0e9530bef4657ffdea",
            "input": "Glucobrassicin (GBS), a glucosinolate contained in many brassica vegetables, is the precursor of chemopreventive compounds such as indole-3-carbinol. Large amounts of GBS would be needed to perform studies aimed at elucidating its role in the diet. This study was mainly undertaken to evaluate the flower buds of Isatis canescens as a source for GBS purification. In order to investigate the health-promoting potential of this species, glucosinolate, phenol and flavonoid content as well as the whole antioxidant capacity were also determined. Flower bud samples were collected in four localities around Mount Etna in Sicily, Italy, where I. canescens is widespread, as they are locally traditionally eaten.', 'I. canescens flower buds displayed high GBS concentrations, up to 60 \u00b5mol g(-1) dry weight. The purification method consisted of two chromatographic steps, which made it possible to obtain GBS with a purity of 92-95%, with a yield of 21 g kg(-1) . The total glucosinolates, phenols, flavonoids and antioxidant activity were considerable, with the southern locality showing the highest concentrations for all the phytochemicals.",
            "output": [
                "Is isatis canescens a rich source of glucobrassicin and other health-promoting compounds?"
            ]
        },
        {
            "id": "task847-46b8e7d7d6334458b335f785aef182ec",
            "input": "Comorbidity is prevalent among patients with Ischemic Heart Disease (IHD) and may influence patients' subjective and objective domains of well-being.\", 'We aimed to investigate the associations between comorbidity and different measures of well-being (i.e. health related quality of life, psychological distress, sleep quality, and dyadic adjustment) among patients with IHD.', 'In this cross-sectional study, 796 outpatients with documented IHD were enrolled from an outpatient cardiology clinic in 2006. Comorbidity (Ifudu index), quality of life (SF36), psychological distress (Hospital Anxiety Depression Scale; HADS), sleep quality (Pittsburg Sleep Quality Index; PSQI), and dyadic adjustment quality (Revised Dyadic Adjustment Scale; RDAS) were measured. Associations between comorbidity and different measures of well-being were determined.', 'Significant correlations were found between comorbidity score and all measures of well-being. Comorbidity score was correlated with physical quality of life (r = -0.471, P < 0.001), mental quality of life (r = -0.447, P < 0.001), psychological distress (r = 0.344, P < 0.001), sleep quality (r = 0.358, P < 0.001), and dyadic adjustment (r = -0.201, P < 0.001).",
            "output": [
                "Does comorbidity influence multiple aspects of well-being of patients with ischemic heart disease?"
            ]
        },
        {
            "id": "task847-3733a08041154bcfa51aa827f13eee06",
            "input": "We previously demonstrated that the lifespan of primary human keratinocytes could be extended indefinitely by culture in the presence of the Rho kinase (ROCK) inhibitor Y-27632. This technique has proven to be very useful in diverse areas of basic and clinical research.', 'In this follow-up study we determine whether the continual presence of Y-27632 is required for sustained proliferation. We also test whether different ROCK inhibitors can be used for this technique and whether it can also promote indefinite proliferation of animal keratinocytes. We measure keratinocyte gene expression, proliferation, behaviour and lifespan in the presence and absence of Y-27632.', 'We demonstrate that the extension of lifespan observed by culture of keratinocytes in the presence of fibroblast feeders and a ROCK inhibitor is reversible and that cells senesce gradually when the inhibitor is removed from the medium. Conversely, keratinocytes that are close to the end of their replicative life span can be revived by ROCK inhibition. We demonstrate that different inhibitors of ROCK can also efficiently extend the lifespan of human keratinocytes and that ROCK inhibition extends the lifespan of animal keratinocytes derived from mouse and bovine epithelia. Gene expression analysis of human epidermal keratinocytes cells grown in the presence of Y-27632 demonstrates that ROCK inhibition primarily inhibits keratinocyte differentiation. Live-imaging of keratinocytes cultured with ROCK inhibitors show that the effect of ROCK inhibition on cellular proliferation is immediate and ROCK inhibited cells proliferate rapidly without differentiation or stratification.",
            "output": [
                "Is the effect of Rho kinase inhibition on long-term keratinocyte proliferation rapid and conditional?"
            ]
        },
        {
            "id": "task847-1a0b5984df3a47f7a99c3f1c2ed23a6b",
            "input": "The molecular identity of calcium-activated chloride channels (CaCCs) in vascular endothelial cells remains unknown. This study sought to identify whether anoctamin-1 (Ano1, also known as TMEM16A) functions as a CaCC and whether hypoxia alters the biophysical properties of Ano1 in mouse cardiac vascular endothelial cells (CVECs).', 'Western blot, quantitative real-time PCR, confocal imaging analysis and patch-clamp analysis combined with pharmacological approaches were used to determine whether Ano1 was expressed and functioned as CaCC in CVECs.', 'Ano1 was expressed in CVECs. The biophysical properties of the current generated in the CVECs, including the Ca(2+) and voltage dependence, outward rectification, anion selectivity and the pharmacological profile, are similar to those described for CaCCs. The density of ICl ( C a) detected in CVECs was significantly inhibited by T16Ainh -A01, an Ano1 inhibitor, and a pore-targeting, specific anti-Ano1 antibody, and was markedly decreased in Ano1 gene knockdown CVECs. The density of ICl ( C a) was significantly potentiated in CVECs exposed to hypoxia, and this hypoxia-induced increase in the density of ICl ( C a) was inhibited by T16Ainh -A01 or anti-Ano1 antibody. Hypoxia also increased the current density of ICl ( C a) in Ano1 gene knockdown CVECs.",
            "output": [
                "Does hypoxia augment the calcium-activated chloride current carried by anoctamin-1 in cardiac vascular endothelial cells of neonatal mice?"
            ]
        },
        {
            "id": "task847-7f8bf62723104b43bec81b62dfa9bdee",
            "input": "Sepsis-induced myocardial injury (SIMI) is caused by a variety of mechanisms. The aim of the study is to investigate the effects of metalloproteinase-8 (MMP-8) on SIMI and its mechanisms in rats.', 'Forty male Sprague Dawley rats were randomly divided into four groups: MMP-8 inhibitor (M8I), dexamethasone (DEX), sepsis, and sham groups. The sepsis model was established by cecal ligation and puncture (CLP). Rats in the M8I group immediately received an intraperitoneal injection of M8I (0.1 mg/kg) after CLP. Rats in the DEX group immediately received an intraperitoneal (IP) injection of DEX (2 mg/kg). Rats in the sepsis and sham groups received intraperitoneal injections of normal saline. Rats were sacrificed 12 hours after CLP. Paraffin sections were stained with hematoxylin and eosin to observe the myocardium. The myocardial ultrastructure was observed with transmission electron microscopy. MMP-8, tumor necrosis factor-\u03b1 (TNF-\u03b1), and interleukin-1\u03b2 (IL-1\u03b2) were detected by immunohistochemistry. The expression of MMP-8 was measured by Western blotting. TNF-\u03b1 and IL-1\u03b2 levels in serum and myocardial tissue were determined by enzyme-linked immunosorbent assay.', 'Compared with the sham group, the myocardium in the sepsis group was seriously injured. MMP-8, TNF-\u03b1 and IL-1\u03b2 expression was higher in the sepsis group than in the sham group. Treatment with M8I or DEX, however, attenuated sepsis induced histopathological changes in the heart, and was associated with significant reductions in serum and myocardial levels of TNF-\u03b1 and IL-1\u03b2 (P < 0.05). M8I significantly inhibited MMP-8 expression in myocardial tissue (P < 0.05). In addition, treatment with DEX was not associated with a change in myocardial levels of MMP-8 (P > 0.05).",
            "output": [
                "Do matrix metalloproteinase-8 inhibitors mitigate sepsis-induced myocardial injury in rats?"
            ]
        },
        {
            "id": "task847-2dfa38b96d9e4e79a95d018bf8c10513",
            "input": "SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear.', 'The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 \u00b5mol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting.', 'Over expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-\u03baB p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-\u03baB p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).",
            "output": [
                "Does metformin ameliorate insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3?"
            ]
        },
        {
            "id": "task847-95d3056a066c4c1ab3efad337fd5d4b4",
            "input": "Tumor cells can reduce the number of dendritic cells (DCs) in the tumor environment and cause DC dysfunction through autocrine or paracrine pathways. We sought to measure cyclooxygenase-2 (COX-2) expression in bombesin-inhibited DCs treated with theanine in vitro and to explore the protection and activation effects of theanine on DCs.', 'Enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting were used to analyze the effects of theanine on COX-2 expression and interleukin (IL)-12/IL-10 secretion of bombesin-treated DCs.', 'DCs acquired an impaired phenotype as a result of bombesin treatment. Theanine increased the expression of mature DC surface molecules. The number of cell apoptosis with the treatment of bombesin and theanine significantly decreased, accounting for 15.9%, compared with 26.1% of cell apoptosis with bombesin. COX-2 expression in bombesin-treated DCs was inhibited by theanine in a dose-dependent manner. Theanine promoted DC secretion of IL-12. IL-12 levels reached (137.4 \u00b1 4.9) pg/ml with theanine at 200 \u00b5mol/L. However, theanine inhibited the secretion of IL-10 in a dose-dependent manner. IL-10 levels were only (58.4 \u00b1 6.9) pg/ml with theanine at 200 \u00b5mol/L.",
            "output": [
                "Does theanine improve the function of dendritic cells via the downregulation of cyclooxygenase-2 expression?"
            ]
        },
        {
            "id": "task847-2bcd145ed8844c43b0d5cc4d337cce82",
            "input": "Central nervous system (CNS) trauma and neurodegenerative disorders trigger a cascade of cellular and molecular events resulting in neuronal apoptosis and regenerative failure. The pathogenic mechanisms and gene expression changes associated with these detrimental events can be effectively studied using a rodent optic nerve crush (ONC) model. The purpose of this study was to use a mouse ONC model to: (a) evaluate changes in retina and optic nerve (ON) gene expression, (b) identify neurodegenerative pathogenic pathways and (c) discover potential new therapeutic targets.', 'Only 54% of total neurons survived in the ganglion cell layer (GCL) 28 days post crush. Using Bayesian Estimation of Temporal Regulation (BETR) gene expression analysis, we identified significantly altered expression of 1,723 and 2,110 genes in the retina and ON, respectively. Meta-analysis of altered gene expression (\u22651.5, \u2264-1.5, p\\u2009<\\u20090.05) using Partek and DAVID demonstrated 28 up and 20 down-regulated retinal gene clusters and 57 up and 41 down-regulated optic nerve clusters. Regulated gene clusters included regenerative change, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. Expression of selected genes (Vsnl1, Syt1, Synpr and Nrn1) from retinal and ON neuronal clusters were quantitatively and qualitatively examined for their relation to axonal neurodegeneration by immunohistochemistry and qRT-PCR.",
            "output": [
                "Does optic nerve crush induce spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice?"
            ]
        },
        {
            "id": "task847-3f1c0dfeaf054c45af5abc62caad1373",
            "input": "Cardiopulmonary exercise stress testing (CPET) is used to grade the severity of heart failure and to assess its prognosis. However it is unknown whether CPET may improve diagnostic accuracy of standard ECG stress testing to identify or exclude obstructive coronary artery disease (O-CAD) in patients with chest pain.', 'We prospectively studied 1265 consecutive subjects (55 \u00b1 8 years, 156 women) who were evaluated with ECG stress testing (ET) for chest pain. No one had a documented O-CAD. All patients performed an incremental CPET with ECG recordings on an electronically braked cycle ergometer.', 'Of 1265 patients, 73 had a positive CPET and 1192 had a negative CPET. Seventy-three patients with a positive CPET and 71 patients with a negative CPET agreed to undergo nuclear SPECT imaging and coronary angiography. Follow-up lasted 48 \u00b1 7 months. As compared with ET, sensitivity, specificity, PPV and NPV were all improved significantly (ET: 48%, 55%, 33%, 95%; CPET: 88%, 98%, 73%, 99%, respectively, P<0.001). Patients with both peak VO2>91% of predicted VO2 max and absence of VO2-related signs of myocardial ischemia had no evidence of O-CAD in 100% of cases. Cardiac events occurred in 32 patients with a positive CPET and 8 patients with a negative CPET (log rank 18.2, P<0.0001).",
            "output": [
                "Is cardiopulmonary exercise testing more accurate than ECG-stress testing in diagnosing myocardial ischemia in subjects with chest pain?"
            ]
        },
        {
            "id": "task847-9ef533aae87f4393a9bfe77ee33e948d",
            "input": "The permanent down-regulated expression of T-cell intracellular antigen (TIA) proteins in HeLa cells improves cytoskeleton-mediated functions such as cell proliferation and tumor growth.', 'Making use of human and mouse cells with knocked down/out expression of T-cell intracellular antigen 1 (TIA1) and/or TIA1 related/like (TIAR/TIAL1) proteins and classical RNA (e.g. reverse transcription-quantitative polymerase chain reaction, polysomal profiling analysis using sucrose gradients, immunoblotting, immunoprecipitation, electrophoretic mobility shift assays, ultraviolet light crosslinking and poly (A+) test analysis) and cellular (e.g. immunofluorescence microscopy and quimeric mRNA transfections) biology methods, we have analyzed the regulatory role of TIA proteins in the post-transcriptional modulation of beta-actin (ACTB) mRNA.', \"Our observations show that the acquisition of above cellular capacities is concomitant with increased expression levels of the actin beta subunit (ACTB) protein. Regulating TIA abundance does not modify ACTB mRNA levels, however, an increase of ACTB mRNA translation is observed. This regulatory capacity of TIA proteins is linked to the ACTB mRNA 3'-untranslated region (3'-UTR), where these proteins could function as RNA binding proteins. The expression of GFP from a chimeric reporter containing human \u0391C\u03a4\u0392 3'-UTR recapitulates the translational control found by the endogenous ACTB mRNA in the absence of TIA proteins. Additionally, murine embryonic fibroblasts (MEF) knocked out for TIA1 rise mouse ACTB protein expression compared to the controls. Once again steady-state levels of mouse ACTB mRNA remained unchanged.",
            "output": [
                "Does long-term reduction of T-cell intracellular antigens lead to increased beta-actin expression?"
            ]
        },
        {
            "id": "task847-6ef49489c15f407e850e32136ee817a8",
            "input": "The use of DNA methylation difference between maternal blood cell and fetal (placental) DNA is one of the main areas of interest for the development of fetal epigenetics markers in maternal plasma.', 'We employed a methylation array (HumanMethylation450 array, Illumina, Inc.) to identify novel biomarkers that are specially hypermethylated in placental DNA versus maternal blood cells in a genome-wide basis. Validation by bisulfite genomic sequencing was performed and the priority was given to potential targets that harbor differential methylated CpG sites overlapped with at least two methylation-sensitive restriction enzyme (MSRE) recognizing sites, as well as one polymorphic single-nucleotide polymorphism (SNP), within a short DNA stretch. Three candidate regions of PSMB8, SKI, and CHST11 gene were selected for developing a preliminary polymerase chain reaction assay with MSRE digestion of maternal plasma DNA. SNP genotypes were confirmed by direct sequencing.', 'We identified 2944 and 5218 fetal-specific hypermethylated CpG sites in the first- and third-trimester placenta, respectively, of which 2613 were overlapped, suggesting a consistency of differential methylation during the whole pregnancy. The array results were confirmed by bisulfite genomic sequencing. The preliminary tests in maternal plasma showed that postdigestion hypermathylated versions of these candidate molecules were detectable only in pregnant women. We further revealed that methylated targets in maternal plasma possessed the fetal SNP genotypes.",
            "output": [
                "Does epigenome-wide DNA methylation assay reveal placental epigenetic markers for noninvasive fetal single-nucleotide polymorphism genotyping in maternal plasma?"
            ]
        },
        {
            "id": "task847-33bc12d82c234eb3aa6d850f3f1eb691",
            "input": "The Notch pathway stabilizes sprouting angiogenesis by favoring stalk cells over tip cells at the vascular front. Because tip and stalk cells have different properties in morphology and function, their transcriptional regulation remains to be distinguished. Transcription factor Sox17 is specifically expressed in endothelial cells, but its expression and role at the vascular front remain largely unknown.', 'To specify the role of Sox17 and its relationship with the Notch pathway in sprouting angiogenesis.', 'Endothelial-specific Sox17 deletion reduces sprouting angiogenesis in mouse embryonic and postnatal vascular development, whereas Sox17 overexpression increases it. Sox17 promotes endothelial migration by destabilizing endothelial junctions and rearranging cytoskeletal structure and upregulates expression of several genes preferentially expressed in tip cells. Interestingly, Sox17 expression is suppressed in stalk cells in which Notch signaling is relatively high. Notch activation by overexpressing Notch intracellular domain reduces Sox17 expression both in primary endothelial cells and in retinal angiogenesis, whereas Notch inhibition by delta-like ligand 4 (Dll4) blockade increases it. The Notch pathway regulates Sox17 expression mainly at the post-transcriptional level. Furthermore, endothelial Sox17 ablation rescues vascular network from excessive tip cell formation and hyperbranching under Notch inhibition in developmental and tumor angiogenesis.",
            "output": [
                "Does notch pathway target proangiogenic regulator Sox17 to restrict angiogenesis?"
            ]
        },
        {
            "id": "task847-ed927870abcc41afa11fccab1b044dcd",
            "input": "Hemodynamic disturbed flow (DF) is associated with susceptibility to atherosclerosis. Endothelial Kruppel-Like Factor 4 (KLF4) is an important anti-inflammatory atheroprotective transcription factor that is suppressed in regions of DF.', 'The plasticity of epigenomic KLF4 transcriptional regulation by flow-mediated DNA methylation was investigated in vitro and in arterial tissue.', 'To recapitulate dominant flow characteristics of atheroprotected and atherosusceptible arteries, human aortic endothelial cells were subjected to pulsatile undisturbed flow or oscillatory DF containing a flow-reversing phase. Differential CpG site methylation was measured by methylation-specific polymerase chain reaction, bisulfite pyrosequencing, and restriction enzyme-polymerase chain reaction. The methylation profiles of endothelium from disturbed and undisturbed flow sites of adult swine aortas were also investigated. In vitro, DF increased DNA methylation of CpG islands within the KLF4 promoter that significantly contributed to suppression of KLF4 transcription; the effects were mitigated by DNA methyltransferase (DNMT) inhibitors and knockdown of DNMT3A. Contributory mechanisms included DF-induced increase of DNMT3A protein (1.7-fold), DNMT3A enrichment (11-fold) on the KLF4 promoter, and competitive blocking of a myocyte enhancer factor-2 binding site in the KLF4 promoter near the transcription start site. DF also induced DNMT-sensitive propathological expression of downstream KLF4 transcription targets nitric oxide synthase 3, thrombomodulin, and monocyte chemoattractant protein-1. In support of the in vitro findings, swine aortic endothelium isolated from DF regions expressed significantly lower KLF4 and nitric oxide synthase 3, and bisulfite sequencing of KLF4 promoter identified a hypermethylated myocyte enhancer factor-2 binding site.",
            "output": [
                "Does hemodynamic disturbed flow induce differential DNA methylation of endothelial Kruppel-Like Factor 4 promoter in vitro and in vivo?"
            ]
        },
        {
            "id": "task847-378de225d30c443295beb7cf859372f8",
            "input": "Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease.', 'In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation). The performance of LSM to predict complications was determined using the c-statistic.', 'Among 2,052 patients (median age 51 years, 65% with hepatitis B or C), 87 patients (4.2%) died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0-23.5 months). Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P<0.00005). The 2-year incidence rates of death or hepatic complications were 2.6%, 9%, 19%, and 34% in patients with liver stiffness <10, 10-19.9, 20-39.9, and \u226540 kPa, respectively (P<0.00005). After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications (hazard ratio [HR] 1.05 per kPa; 95% confidence interval [CI] 1.03-1.06). The c-statistic of liver-stiffness for predicting complications was 0.80 (95% CI 0.75-0.85). A liver stiffness below 20 kPa effectively excluded complications (specificity 93%, negative predictive value 97%); however, the positive predictive value of higher results was sub-optimal (20%).",
            "output": [
                "Does liver stiffness by transient elastography predict liver-related complications and mortality in patients with chronic liver disease?"
            ]
        },
        {
            "id": "task847-6ef80ee6bffd4a97bd85eda4db5efd53",
            "input": "Hypoxia can induce autophagy, which plays an important role in cardioprotection. The present study tested the hypothesis that patients with congenital heart disease living at a high altitude could resist ischemia-reperfusion injury better than those at a low altitude, through elevated basal autophagy by chronic hypoxia.', 'Twelve Tibetan patients residing at a high altitude of >3000 m and 12 Han patients residing at a low altitude of <500 m with simple atrial or ventricular septal defects were prospectively recruited. All patients underwent cardiopulmonary bypass, maintaining a flow rate of approximately 2.4 to 2.8 L/min/m2 and mean arterial pressure of \u226540 to 60 mm Hg. Myocardial ischemia-reperfusion injury between the 2 groups was compared using cardiac troponin I, brain natriuretic peptide, hematoxylin eosin staining, and the terminal deoxynucleotidyl transferase dUTP nick end labeling test. Autophagy-related proteins microtubule-associated protein 1 light chain 3 II (LC3II), Beclin1, and lysosomal-associated membrane protein 2 (LAMP2) and their upstream protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) were evaluated with Western blotting.', 'The maximal cardiac troponin I concentration and increasing x-fold of brain natriuretic peptide in the high-altitude group were obviously lower than those in the low-altitude group (3.10\u00b10.77 vs 7.10\u00b12.28 ng/mL and 2.51\u00b10.94 vs 14.66\u00b16.83, respectively). The preoperative and postoperative levels of LC3II, LAMP2, and upstream Bnip3 in the high-altitude group were obviously greater. No difference was found in the Beclin1 level between the 2 groups at baseline or ischemia-reperfusion.",
            "output": [
                "Does high basal level of autophagy in high-altitude residents attenuate myocardial ischemia-reperfusion injury?"
            ]
        },
        {
            "id": "task847-fd88a7bb92c94b02872218e15fb0aa02",
            "input": "Behavioral studies of spatial navigation in aging indicate that orientation using an allocentric reference frame (object-centered orientation) is impaired, whereas orientation using egocentric processes (self-centered orientation) is not. It has been proposed that navigational deficits may result from more general alterations of perception and attention or executive functions. The purpose of this study is to assess allocentric and egocentric representation in elderly individuals, and to determine if age-related deficits in spatial navigation are related to an attentional decline.', 'We assessed encoding of the position of geometrical shapes, depending specifically on an allocentric or egocentric reference frame, during ERP recording in young and old subjects.', 'Aging was associated with a performance decline in allocentric, but not egocentric, encoding. Both allocentric and egocentric conditions elicited parietal early components P1 and N1, reflecting top-down modulation, and components P2 and N2, reflecting selective attention and stimulus categorization. We observed age-associated effects on N1 and N2 amplitudes and on N2 latency in both spatial conditions. Moreover, impaired allocentric performance in older subjects was associated with a greater P2 amplitude and delayed P2 latency compared with younger subjects.",
            "output": [
                "Is allocentric but not egocentric orientation impaired during normal aging : an ERP study?"
            ]
        },
        {
            "id": "task847-c62600f1beb34c0192770d131413553a",
            "input": "Air pollution is a major health challenge worldwide and has previously been strongly associated with adverse reproductive health. This study aimed to examine the association between spontaneous abortion and seasonal variation of air pollutants in Ulaanbaatar, Mongolia.', 'Monthly average O3, SO2, NO2, CO, PM10 and PM2.5 levels were measured at Mongolian Government Air Quality Monitoring stations. The medical records of 1219 women admitted to the hospital due to spontaneous abortion between 2009-2011 were examined retrospectively. Fetal deaths per calendar month from January-December, 2011 were counted and correlated with mean monthly levels of various air pollutants by means of regression analysis.', 'Regression of ambient pollutants against fetal death as a dose-response toxicity curve revealed very strong dose-response correlations for SO2 r\\u2009>\\u20090.9 (p\\u2009<\\u20090.001) while similarly strongly significant correlation coefficients were found for NO2 (r\\u2009>\\u20090.8), CO (r\\u2009>\\u20090.9), PM10 (r\\u2009>\\u20090.9) and PM2.5 (r\\u2009>\\u20090.8), (p\\u2009<\\u20090.001), indicating a strong correlation between air pollution and decreased fetal wellbeing.",
            "output": [
                "Does seasonal ambient air pollution correlate strongly with spontaneous abortion in Mongolia?"
            ]
        },
        {
            "id": "task847-d5c1f8a38df449b1b87bd39458842552",
            "input": "Controversy exists over whether or not single-needle liver biopsies are sufficient to compare histological parameters in patients with non-alcoholic fatty liver disease.', 'To identify sampling variability, we biopsied four liver specimens per patient, based on biopsy size (needle vs wedge) and location (left vs right lobe), immediately prior to bariatric Roux-en-Y gastric bypass surgery.', \"Ten prospectively enrolled, morbidly obese patients underwent 40 laparoscopy-guided biopsies; two needle and two wedge from each of 16 left and 16 right liver lobes. The Kappa coefficient for concordance compared histological parameters from left and right lobe needle- and wedge biopsies. Wedge biopsies were considered our 'Gold Standard'.\", 'Each patient had two wedge- and two needle liver biopsies. Kappa concordance between all needle and wedge biopsies from right and left lobes showed variability. Wedge- and needle liver biopsies from contralateral lobes had higher concordance with each other, compared to ipsilateral needle/wedge biopsy pairs. Contralateral wedge pairs had higher concordance than contralateral needle/needle pairs. There were no biopsy complications.",
            "output": [
                "Do wedge and needle liver biopsies show discordant histopathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery?"
            ]
        },
        {
            "id": "task847-9d84dec1db324eaf917283b7548ed15b",
            "input": "To identify predictive factors associated with the improvement of social functioning of schizophrenia patients in a community.', '101 schizophrenia patients undergoing community rehabilitation were assessed with the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Self-Esteem Scale (SES), Family Function Questionnaire (APGAR), and the World Health Organization Disability Assessment Scale II (WHODAS-II) twice 6 months apart. Pearson correlation and hierarchical multiple linear regression analyses were performed to identify the influencing and predictive factors associated with the improvement of social functioning.', 'The increase of PSP score was correlated with age (r = 0.220), reduced PANSS negative score (r = 0.468), reduced PANSS general score (r = 0.392), reduced PANSS total score (r = 0.472), and reduced WHODAS-II Score (r = 0.247). The predictive factors of the change of PSP score followed the following order: change of PANSS negative score [the change of coefficient of determination (deltaR2 ) = 0.197], age of onset (deltaR2 = 0.048), change of WHODAS-II score and psychiatric rehabilitation (deltaR2 = 0.031).",
            "output": [
                "Do [ Negative symptoms predict the improvement of social functioning of patients with schizophrenia ]?"
            ]
        },
        {
            "id": "task847-fc13b143a4cf450c8789471d4e8ede68",
            "input": "To demonstrate bioequivalence of linagliptin/metformin fixed-dose combination (FDC) tablets and the corresponding combination of individual tablets taken together, i.e., free-pill (FP) treatment.', 'Three dosing combinations were evaluated in three separate randomized studies: linagliptin 2.5 mg with 500 mg, 850 mg, or 1,000 mg metformin. These studies used a prospective, open-label, randomized, two-way crossover design to evaluate bioequivalence in healthy volunteers (n = 287). After an overnight fast, participants received an FDC tablet once, and on a separate visit received the corresponding FP treatment. The two possible treatment sequences (FDC/FP and FP/FDC) were randomly allocated to the participants. A washout period of 35 days separated the two study treatments. The primary endpoints were maximum plasma concentration (Cmax) of linagliptin and metformin, area under the plasma concentration time curve from 0 to 72 hours (AUC0-72) for linagliptin, and from 0 to infinity (AUC0-inf) for metformin.', 'The 90% confidence intervals of the adjusted geometric mean ratios of Cmax and AUC (calculated as FDC/ FP) were within the bioequivalence acceptance limits of 80 - 125%. The number of participants reporting at least one adverse event following FDC treatments was comparable to, or less than, that following FP treatments. Evaluation of vital signs and clinical laboratory tests revealed no safety issues.",
            "output": [
                "Is linagliptin fixed-dose combination with metformin bioequivalent to co-administration of linagliptin and metformin as individual tablets?"
            ]
        },
        {
            "id": "task847-aa082cb3a89f416895a386cffed73bc0",
            "input": "Although the C5 variant of cholinesterase is known to be a cause of hypercholinesterasemia, the pathophysiological significance of the C5 variant and the C5 variant-related hypercholinesterasemia in cardiovascular diseases remain unclear. The present study aimed to clarify the pathophysiological significance of the C5 variant as a risk or protective factor for coronary artery disease (CAD) in patients with severe hypercholinesterasemia.', 'Severe hypercholinesterasemia was defined as serum cholinesterase (ChE) activity >= 450 IU/L (>= 2.0 SD). We screened 11,648 consecutive outpatients between 2005 and 2011 at Toho University, Sakura Medical Center. In patients with severe hypercholinesterasemia, phenotyping of the C5 variant was conducted using polyacrylamide gel electrophoresis and alpha-naphthyl butyrate staining.', '157 subjects (1.4% of 11,648 outpatients screened) were diagnosed with severe hypercholinesterasemia (mean serum ChE activity 574 \u00b1 109 IU/L), and the frequency of the C5 variant was 45.2%. Subjects with the C5 variant had higher age, lower body mass index, milder dyslipidemia and liver dysfunction, and lower rates of hypertension and CAD compared with subjects without the C5 variant. Multivariate logistic regression model demonstrated that the presence of C5 variant independently lowered the risk of CAD, with odds ratio 0.071 (95% confidence interval (CI) 0.007 - 0.763, p = 0.029).",
            "output": [
                "Is c5 variant associated with decreased risk of coronary artery disease in outpatients with severe hypercholinesterasemia?"
            ]
        },
        {
            "id": "task847-3490de15fbaf4fb9a67bd5dce9268e18",
            "input": "Coronary heart disease is the second cause of death in Chilean women, with higher mortality among women, especially at younger ages. The objective was to analyze in-hospital case-fatality by sex and age in patients with acute myocardial infarction in Chile and to evaluate associated factors.', 'From the nationwide hospital admissions database and the GEMI registry (a multicenter registry), we selected all cases of acute myocardial infarction (code: I.21) that occurred between 2001 and 2007 in Chile. We estimated odds ratios for in-hospital case-fatality in women by age (crude and adjusted for clinical characteristics and treatment).', 'In total, 49,287 cases of acute myocardial infarction were hospitalized, 31.3% of them women; 9278 patients were incorporated in the GEMI registry (27.1% women). In-hospital case-fatality was higher (P<.001) in women than men (national database, 20.4% vs 11.3%; GEMI, 14.2% vs 7.3%, irrespective of age. In-hospital case-fatality risk was higher in women aged<45 years: national odds ratio=2.3 (95% confidence interval, 1.5-3.3) and GEMI, odds ratio=2.7 (1.1-6.8). The estimated risk was lower in women aged 75 or more years in both databases, 1.3 (1.2-2.4) and 1.5 (1.2-1.9), respectively. Younger women less often received statins, odds ratio=0.7 (0.6-0.8); acetylsalicylic acid, odds ratio=0.4 (0.2-0.6); betablockers, odds ratio=0.8 (0.6-0.9), and thrombolytics, odds ratio=0.6 (0.5-0.8). An interaction was found between Killip class and sex. After adjusting for covariates, women aged<55 years with ST-segment elevation myocardial infarction and Killip class I-II, had the highest risk, odds ratio=4.3 (2.1-8.9).",
            "output": [
                "Do younger women have a higher risk of in-hospital mortality due to acute myocardial infarction in Chile?"
            ]
        },
        {
            "id": "task847-26702579896243e888643b6cfcc05d0f",
            "input": "We hypothesized that miR-194 may control Forkhead box protein M1 (FoxM1) expression in gastric cancer cells and therefore may have therapeutic potential in gastric cancer.', 'The expression level of miR-194 was examined using real-time PCR in human gastric cancer and noncancerous gastric tissues, gastric cancer cell and normal gastric mucosal epithelial cell. We examined whether the miR-194 regulates cell migration and invasion, and the epithelial-mesenchymal transition Phenotype by inhibiting FoxM1 in gastric cancer cells.', 'The expression of miR-194 was significantly lower in gastric cancer compared with non-cancerous gastric tissues and cells. Exogenous expression of miR-194 inhibited cell migration, invasion, and the epithelial-mesenchymal transition phenotype in gastric cancer cells. Moreover, we discovered a novel post-transcriptional regulatory mechanism of FoxM1 expression that is mediated by miR-194.",
            "output": [
                "Does microRNA-194 inhibit the epithelial-mesenchymal transition in gastric cancer cells by targeting FoxM1?"
            ]
        },
        {
            "id": "task847-6613737e42374443969edf13fc875a09",
            "input": "To evaluate the effect of Ac-hE-18A-NH2 on TNF-\u03b1 secretion and mRNA expression in ox-LDL-stimulated RAW264.7 macrophages and to elucidate the possible mechanisms.', \"Macrophages were incubated in the medium containing various concentrations of Ac-hE18A-NH2 (1-50 \u03bcg/mL) with ox-LDL (50 \u03bcg/mL) stimulated. The TNF-\u03b1 level and intracellular cholesterol content were measured by commercially available quantitation kits following the manufacturer's instructions. TNF-\u03b1 and ATP-binding cassette transporter A1 (ABCA1) mRNA expression were detected by real-time PCR. ABCA1 and I\u03baB protein -expression in the macrophages were determined by Western blot. NF-\u03baB activity was evaluated by electrophoretic mobility shift assay (EMSA).\", 'Ox-LDL stimulation induced a significant increase in TNF-\u03b1 secretion, mRNA expression, cholesterol accumulation and nuclear factor-\u03baB (NF-\u03baB) activity in RAW264.7 macrophages. Ac-hE-18A-NH2 reduced TNF-\u03b1 secretion and mRNA expression, up-regulated the ABCA1 mRNA and protein expression, reduced the intracellular cholesterol content, and inhibited NF- \u03baB activation in a dose-dependent manner. Under the same condition and the same concentration, Ac-hE-18A-NH2 was more efficient than D-4F (apoA-I mimetic peptide) in inhibiting the inflammatory response induced by ox-LDL in the macrophages.",
            "output": [
                "Does [ Ac-hE-18A-NH2 inhibit the inflammatory response induced by ox-LDL via inhibiting NF-\u03baB activation in RAW264.7 macrophages ]?"
            ]
        },
        {
            "id": "task847-551b2f4818e14d16a11dc2b86e703f30",
            "input": "Antigen-specific anti-tumor vaccines have demonstrated clinical efficacy, but immunological and clinical responses appear to be patient-dependent. We hypothesized that naturally-occurring differences in amino acid sequence of a host's target antigen might predict for immunological outcome from genetic vaccination by presentation of epitopes different from the vaccine.\", 'Using peripheral blood cells from 33 patients who had been treated with a DNA vaccine encoding prostatic acid phosphatase (PAP), we sequenced the exons encoding PAP and PSA genes from somatic DNA to identify single nucleotide polymorphisms. In addition, mRNA was collected to detect alternative splice variants of PAP.', 'We detected four synonymous coding mutations of PAP among 33 patients; non-synonymous coding mutations were not identified. Alternative splice variants of PAP were detected in 22/27 patients tested. The presence of detectable splice variants was not predictive of immunological outcome from vaccination. Immune responses to peptides encoded by these splice variants were common (16/27) prior to immunization, but not associated with immune responses elicited with vaccination.",
            "output": [
                "Do presence of antigen-specific somatic allelic mutations and splice variants predict for immunological response to genetic vaccination?"
            ]
        },
        {
            "id": "task847-3ba75edfeec94607bb948f1b45581073",
            "input": "The medicinal leech is considered as a complementary and appropriate model to study immune functions in the central nervous system (CNS). In a context in which an injured leech's CNS can naturally restore normal synaptic connections, the accumulation of microglia (immune cells of the CNS that are exclusively resident in leeches) has been shown to be essential at the lesion to engage the axonal sprouting. HmC1q (Hm for Hirudo medicinalis) possesses chemotactic properties that are important in the microglial cell recruitment by recognizing at least a C1q binding protein (HmC1qBP alias gC1qR).\", 'Recombinant forms of C1q were used in affinity purification and in vitro chemotaxis assays. Anti-calreticulin antibodies were used to neutralize C1q-mediated chemotaxis and locate the production of calreticulin in leech CNS.', 'A newly characterized leech calreticulin (HmCalR) has been shown to interact with C1q and participate to the HmC1q-dependent microglia accumulation. HmCalR, which has been detected in only some microglial cells, is consequently a second binding protein for HmC1q, allowing the chemoattraction of resident microglia in the nerve repair process.",
            "output": [
                "Does calreticulin contribute to C1q-dependent recruitment of microglia in the leech Hirudo medicinalis following a CNS injury?"
            ]
        },
        {
            "id": "task847-74ca062570fe4c5aab371996079531f5",
            "input": "Receptor down-regulation by the multivesicular body (MVB) pathway is critical for many cellular signaling events. MVB generation is mediated by the highly conserved ESCRT (0, I, II, and III) protein complexes. Chmp1 is an ESCRT-III component and a putative tumor suppressor in humans. However, published data on Chmp1 activity are conflicting and its role during tissue development is not well defined.', 'We investigated the function of Drosophila Chmp1 and found that it is an essential gene. In the wing, loss of Chmp1 activity causes a cell fate change from intervein to vein, and interactions between Chmp1 and Drosophila Epidermal Growth Factor Receptor (DER) regulators suggest that Chmp1 negatively regulates DER signaling. Chmp1 knockdown also decreases Blistered expression, which is repressed by DER signaling. We find that Chmp1 protein localizes to the late endosome in Drosophila embryos, which is consistent with its effects on DER signaling resulting from its function in the ESCRT-III complex.",
            "output": [
                "Does the Drosophila Chmp1 protein determine wing cell fate through regulation of epidermal growth factor receptor signaling?"
            ]
        },
        {
            "id": "task847-28498b0fd97343b4b360c9adabb84223",
            "input": "All-oral regimens combining different classes of direct-acting antivirals (DAA) are highly effective for treatment of patients with chronic hepatitis C. NS5A inhibitors will likely form a component of future interferon-sparing treatment regimens. However, despite their potential, the detailed mechanism of action of NS5A inhibitors is unclear. To study their mechanisms, we compared their kinetics of antiviral suppression with those of other classes of DAA, using the hepatitis C virus genotype 1a cell culture-infectious virus H77S.3.', 'We performed detailed kinetic analyses of specific steps in the hepatitis C virus life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors. Assays were designed to measure active viral RNA synthesis and steady-state RNA abundance, polyprotein synthesis, virion assembly, and infectious virus production.', 'Despite their high potency, NS5A inhibitors were slow to inhibit viral RNA synthesis compared with protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations. In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, with onset of inhibition as early as 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly.",
            "output": [
                "Do kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors?"
            ]
        },
        {
            "id": "task847-fafa150934a24e9ba3d0bc4b452e7809",
            "input": "Previous magnetic resonance imaging (MRI) studies have demonstrated increased iron deposition in the basal ganglia of multiple sclerosis (MS) patients. However, it is not clear whether these alterations are associated with changes of iron metabolism in body fluids.', 'The purpose of this study was to investigate if iron metabolism markers in cerebrospinal fluid (CSF) and serum of clinically isolated syndrome (CIS) and MS patients differ from controls and how they relate to clinical and imaging parameters.', 'We analysed serum ferritin, transferrin and soluble transferrin-receptor and CSF ferritin and transferrin by nephelometry in non-anaemic CIS (n=60) or early MS (n=14) patients and 68 controls. In CIS/MS we additionally assessed the T2 lesion load.', 'CSF transferrin was significantly decreased in CIS/MS compared to controls (p<0.001), while no significant differences were seen in serum. Higher CSF transferrin levels correlated with lower physical disability scores (r= -0.3, p<0.05). CSF transferrin levels did not correlate with other clinical data and the T2 lesion load.",
            "output": [
                "Are cerebrospinal fluid transferrin levels reduced in patients with early multiple sclerosis?"
            ]
        },
        {
            "id": "task847-ccb11337a1d643d2a3d1249bb6838aff",
            "input": "The aim of the study was to verify early and definitive outcome of radioiodine therapy in patients with Graves' disease, administering 131I calculated dose to pursue euthyroidism.\", \"We retrospectively analyzed 639 patients affected by Graves' disease and treated by one or more 131I calculated doses. Results dose by dose are reported. As to the first administration, outcome is related to parameters used to calculate dose and to patients' available features. Failures and hypothyroidism onset are evaluated.\", 'A mean dose of 10 mCi shows great effectiveness: 75% of patients were cured after one administration, 88% after two. Of the failures, 84.1% occurred in a mean time of 0.34\u00b10.23 years and were more frequent for larger glands, accelerated intra-gland radioiodine turnover, ophtalmopathy, administration of antithyroid drugs until 131I therapy. Of hypothyroid patients, 39.8% were diagnosed within the first year. After a sharp initial rise, hypothyroidism occurred at a slower rate, with estimated yearly increases of 3.8% until 10 years and of 1.8% later. In still followed up patients, euthyroidism was observed in about half the population after 10 years and in a third after 25 years.",
            "output": [
                "Is 131I therapy and Graves ' disease in a long term observation : euthyroidism a suitable goal . Our experience?"
            ]
        },
        {
            "id": "task847-aa36671506d548788ce80ccb299ee78a",
            "input": "Reactive oxygen species (ROS) are associated with aging. Astaxanthin (AST) is a strong antioxidant and has been reported to prevent various ROS-induced diseases. In the current study, we investigated the effect of AST on age-associated histological and mRNA changes of vocal folds.', 'Prospective animal experiment with control.', 'Six-month-old Sprague-Dawley rats were fed on a normal powder diet with 0.01% (w/w) AST (aged AST-treated group) or without AST (aged sham-treated group). After 12 months of feeding, the larynges were harvested for histology, immunohistochemical detection of 4-hydroxy-2-nonenal (4-HNE), and quantitative real-time polymerase chain reaction for basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Thirteen-week-old rats were used as a young control group (young group).', 'The expression of 4-HNE, an oxidative stress marker, significantly increased in the two aged groups compared with the young group. Histological examination showed that the deposition of hyaluronic acid in the lamina propria (LP) was significantly reduced in the aged sham-treated group compared with the young group, but no significant difference was observed between the aged AST-treated group and the young group. There were no significant differences in the mRNA expression of bFGF and HGF between the aged AST-treated group and the young group, although the expression of these genes was significantly reduced in the aged sham-treated group as compared with the young group.",
            "output": [
                "Does effect of AST on age-associated changes of vocal fold in a rat model?"
            ]
        },
        {
            "id": "task847-305a2cd1ff1645e6ac95018002b69e59",
            "input": "Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10% of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease.', 'We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family.', 'We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene (COQ6) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6-deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells.",
            "output": [
                "Is a germline missense mutation in COQ6 associated with susceptibility to familial schwannomatosis?"
            ]
        },
        {
            "id": "task847-341f3acba6f14ce9962b5b1545440b4d",
            "input": "Reducing ultraviolet radiation exposure may decrease melanoma risk in the hereditary melanoma setting. It is unknown whether genetic counseling and test reporting of CDKN2A/p16 mutation status promote long-term compliance with photoprotection recommendations, especially in unaffected mutation carriers.', 'This study evaluated changes 2 years following melanoma genetic testing in self-reported practice of sun protection (sunscreen, photoprotective clothing, and ultraviolet radiation avoidance) among 37 members of two CDKN2A/p16 kindreds (10 unaffected carriers, 11 affected carriers, and 16 unaffected noncarriers; response rate = 64.9% of eligible participants).', 'Multivariate profile analysis indicated that all three participant groups reported increased daily routine practice of sun protection 2 years following melanoma genetic testing (P < 0.02), with 96.9% reporting that at least one sun protection behavior was part of their daily routine, up from 78.1% at baseline (P < 0.015). Unaffected carriers (P < 0.024) and unaffected noncarriers (P < 0.027) reported significantly more frequent use of photoprotective clothing. Affected carriers maintained adherence to all sun protection behaviors. Reported sunburns in the past 6 months decreased significantly (P < 0.018).",
            "output": [
                "Do unaffected family members report improvements in daily routine sun protection 2 years following melanoma genetic testing?"
            ]
        },
        {
            "id": "task847-bbf483e7beb8411aa0f0f8406feccc83",
            "input": "We investigated the clinical significance of GALNT4 expression in patients with clear cell renal cell carcinoma.', 'Enrolled in this study were 104 patients treated with curative nephrectomy at Zhongshan Hospital, Shanghai during 2004. Of the cohort 23 patients died of disease, 33 experienced recurrence and 3 died of another cause. GALNT4 density was assessed by immunohistochemistry in patient specimens. Univariate and multivariate Cox models, and ROC analysis were used to analyze the impact of prognostic factors on overall and relapse-free survival. Kaplan-Meier analysis with the log rank test was done to compare clinical outcomes between subgroups.', 'Intratumor GALNT4 expression was significantly lower than peritumor expression. Low GALNT4 expression was associated with poor overall and relapse-free survival (p = 0.001 and 0.004, respectively). Intratumor GALNT4 expression, which negatively correlated with tumor size (p = 0.032), necrosis (p\\xa0=\\xa00.013) and TNM stage (p = 0.017), was an independent prognostic indicator for overall and relapse-free survival (HR 3.088, p = 0.020 and 2.173, p = 0.047, respectively). Extending the TNM staging system according to GALNT4 expression showed a better prognostic value for overall and relapse-free survival (AUC 0.786, p = 0.029 and 0.761, p = 0.040, respectively).",
            "output": [
                "Does gALNT4 predict clinical outcome in patients with clear cell renal cell carcinoma?"
            ]
        },
        {
            "id": "task847-c9256b044a874988b8a4026e58617fa4",
            "input": "Human cytomegalovirus (HCMV) can cause congenital infection with risk of neurological disability. Maternal-fetal transmission is associated with placental inflammation. 5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of Leukotrienes (LTs), which are proinflammatory mediators. This study investigated the effect of HCMV infection on 5-LO expression and Leukotriene-B4 (LTB4) induction in human placentae and umbilical vein endothelial cells (HUVEC).', 'Seven placentae from fetuses with congenital HCMV infection and brain damage and six controls were stained with HCMV-immediate-early-antigen (HCMV-IEA) and 5-LO by immunohistochemistry. 5-hydroxyeicosatetraenoic acid (5-HETE) and LTB4 were measured in culture supernatant from ex vivo HCMV-infected placental histocultures by liquid chromatography. In vitro, HCMV infected HUVEC cells were analyzed for 5-LO mRNA and protein expression by real time PCR and immunofluorescence staining.', 'HCMV-IEA was abundant in all HCMV infected placentae but absent in control placentae. 5-LO expression was higher in endothelial and smooth muscle cells of HCMV-infected placentae, compared to control placentae. HCMV infection induced an up-regulation of LTB4 in ex vivo placental explants with higher levels of LTB4 at 72 h compared to controls (p = 0.002). In vitro, 5-LO transcript and protein expression were significantly induced in HCMV-infected HUVEC, compared to the control cultures (p = 0.036).",
            "output": [
                "Does human cytomegalovirus infection induce leukotriene B4 and 5-lipoxygenase expression in human placentae and umbilical vein endothelial cells?"
            ]
        },
        {
            "id": "task847-e3ea0fa0824046658349075d3253ef42",
            "input": "A predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1%) or diffusing capacity of the lung for carbon monoxide (DLCO%) of <40% has traditionally been considered to convey a high risk of lobectomy owing to elevated postoperative morbidity and mortality. These recommendations, however, were largely derived from the pre-video-assisted thoracoscopic surgical (VATS) era. We hypothesized that VATS lobectomy would be associated with acceptable morbidity and mortality at ppoFEV1% and ppoDLCO% values\\xa0<\\xa040%.', 'PpoFEV1% and ppoDLCO% were calculated for patients undergoing open or VATS lobectomy for lung cancer in the Society of Thoracic Surgeons General Thoracic database from 2009 to 2011. Univariate comparisons, multivariate analyses, and 1:1 propensity matching were performed.', 'A total of 13,376 patients underwent lobectomy (50.9% open, 49.1% VATS). A decreased ppoFEV1% and ppoDLCO% were each independent predictors for both cardiopulmonary complications and mortality in the open group (all P \u2264 .008). In the VATS group, ppoFEV1% was an independent predictor of complications (P\\xa0=\\xa0.001) but not mortality (P\\xa0=\\xa0.77), and ppoDLCO% was an independent predictor of complications (P\\xa0=\\xa0.046) and mortality (P\\xa0=\\xa0.008). With decreasing ppoFEV1% or ppoDLCO%, complications and mortality increased at a greater rate in the open lobectomy than in a propensity-matched VATS group (n\\xa0=\\xa04215 each). For patients with ppoFEV1%\\xa0<\\xa040%, mortality was greater in the open (4.8%) than in the matched VATS group (0.7%, P\\xa0=\\xa0.003). Similar results were seen for ppoDLCO%\\xa0<\\xa040% (5.2% open, 2.0% VATS, P\\xa0=\\xa0.003). The rate of complications was significantly greater at ppoFEV1%\\xa0<\\xa040% in the open (21.9%) than in the matched VATS (12.8%, P\\xa0=\\xa0.005) group and similar results were seen with ppoDLCO%\\xa0<\\xa040% (14.9% open, 10.4% VATS, P\\xa0=\\xa0.016).",
            "output": [
                "Is thoracoscopic lobectomy associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40 % of normal?"
            ]
        },
        {
            "id": "task847-0da870cc4d73412c861b5d9c723c5e12",
            "input": "Several retinal ischemic diseases can cause neovascular glaucoma (NVG). Trabeculectomy with mitomycin C (MMC) is a relatively better treatment modality in the management of eyes with NVG than other glaucoma surgeries. The aim of this study was to investigate the factors that may influence the outcome of trabeculectomy with MMC for NVG.', 'Forty-nine NVG eyes from 43 patients (26 males and 17 females) underwent primary trabeculectomy with MMC. The mean follow-up period was 16.8 \u00b1 8.1 months (range, 6 to 34 months). Twenty-one eyes of 21 patients received intravitreal bevacizumab (IVB) 3.6 \u00b1 1.8 days before trabeculectomy with MMC. A Kaplan-Meier survival-curve analysis was used to summarize the cumulative probability of success. We examined the relationship between the surgical outcome and the following surgical factors: gender, age, history of panretinal photocoagulation, history of cataract surgery, history of vitrectomy, preoperative IVB, NVG in the fellow eye, and postoperative complications (hyphema, choroidal detachment, and formation of fibrin) by multivariate analysis.', 'The survival rate was 83.7% after 6 months, 70.9% after 12 months, and 60.8% after 24 months. The Kaplan-Meier survival curves showed no significant difference in the survival rate between the eyes with preoperative IVB (n = 21) and the eyes without preoperative IVB (n = 28) (p = 0.14). The multiple logistic regression analysis showed that postoperative hyphema (odds ratio, 6.54; 95% confidence interval, 1.41 to 35.97) was significantly associated with the surgical outcome (p = 0.02).",
            "output": [
                "Is hyphema a risk factor for failure of trabeculectomy in neovascular glaucoma : a retrospective analysis?"
            ]
        },
        {
            "id": "task847-df82b4afc9dd4f40bb4fa9b49080eed7",
            "input": "To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients.\", 'Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-\u03b2 (TGF-\u03b2) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities.', 'Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p\\u2009<\\u20090.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p\\u2009<\\u20090.01) and definite SSc patients (p\\u2009<\\u20090.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed.",
            "output": [
                "Is early systemic sclerosis : serum profiling of factors involved in endothelial , T-cell , and fibroblast interplay marked by elevated interleukin-33 levels?"
            ]
        },
        {
            "id": "task847-cfa9940a33fe4c779eeed704caf0e3f3",
            "input": "Reactive oxygen species (ROS) are involved in a wide range of cellular processes. However, few studies have examined the generation and function of ROS in human embryonic vascular development. In this study, the sources of ROS and their roles in the vascular differentiation of human embryonic stem cells (hESCs) were investigated.', 'During vascular differentiation of hESCs, CD34(+) cells had quiescence-related gene expression profiles and a large fraction of these cells were in G0 phase. In addition, levels of ROS, which were primarily generated through NOX4, were substantially higher in hESC-derived CD34(+) cells than in hESC-derived CD34(-) cells. To determine whether excess levels of ROS induce quiescence of hESC-derived CD34(+) cells, ROS levels were moderately reduced using selenium to enhance antioxidant activities of thioredoxin reductase and glutathione peroxidase. In comparison to untreated CD34(+) cells, selenium-treated CD34(+) cells exhibited changes in gene expression that favoured cell cycle progression, and had a greater proliferation and a smaller fraction of cells in G0 phase. Thus, selenium treatment increased the number of hESC-derived CD34(+) cells, thereby enhancing the efficiency with which hESCs differentiated into vascular endothelial and smooth muscle cells.",
            "output": [
                "Do reactive oxygen species regulate the quiescence of CD34-positive cells derived from human embryonic stem cells?"
            ]
        },
        {
            "id": "task847-a32f5dde8e7347f4aa2264c8145d32b9",
            "input": "Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH.', 'We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region.', 'We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 \u00d7 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 \u00d7 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 \u00d7 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 \u00d7 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 \u00d7 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits.",
            "output": [
                "Does genome-wide association study identify variants associated with autoimmune hepatitis type 1?"
            ]
        },
        {
            "id": "task847-25bd6772028044438aaa23622af3bd9d",
            "input": "To determine whether motor development at 3 months of age is associated with cognitive, motor, and behavioural outcomes in healthy children at early school age.', 'In this cohort study, we included 74 term-born, healthy children (44 males, 30 females; median gestational age 40.1 wks, range 38.0-42.6 wks). From video recordings (median 12.9 wks, range 9.3-18.6 wks), we assessed the quality of fidgety movements, and calculated a motor optimality score. At school age (median 5 y 11 mo, range 5 y 8 mo-7 y 6 mo), we performed detailed cognitive, motor, and behavioural assessments. We examined whether aspects of motor development were associated with functional outcomes.', 'An age-adequate motor repertoire, in particular the presence of antigravity, midline leg, and manipulation movements, was related to poorer cognition, whereas variable finger postures was related to better cognition. Children with a monotonous concurrent motor repertoire had better ball skills but experienced more behavioural problems. The presence of antigravity movements tended to be associated with abnormal recognition (odds ratio [OR] 4.4, 95% confidence interval [CI], 0.9-21; R(2) =0.17; p=0.070), where the absence of variable finger postures was associated with borderline and abnormal visual-spatial perception (OR 20, 95% CI, 1.7-238; R(2) =0.39; p=0.018).",
            "output": [
                "Is motor development in 3-month-old healthy term-born infants associated with cognitive and behavioural outcomes at early school age?"
            ]
        },
        {
            "id": "task847-81de2ac474b9429bbd46661acfbdc4ec",
            "input": "Although serine proteases and agonists of protease-activated receptor 2 (PAR2) cause inflammation and pain, the spectrum of proteases that are activated by proinflammatory and algesic stimuli and their contribution to inflammatory pain are uncertain.', 'Enzymic assays and selective inhibitors were used to characterize protease activity in mice after intraplantar injections of formalin, bradykinin, PAR2 activating peptide (AP) or vehicle. The capacity of these proteases and of recombinant mouse trypsin 4 to cleave fragments of PAR2 and to activate PAR2 in cell lines was determined. Protease inhibitors and par2 (-/-) mice were used to assess the contributions of proteases and PAR2 to pain and inflammation.', 'Intraplantar injection of formalin, bradykinin or PAR2-AP led to the activation of proteases that were susceptible to the serine protease inhibitor melagatran but resistant to soybean trypsin inhibitor (SBTI). Melagatran inhibited mouse trypsin 4, which degraded SBTI. Proteases generated in inflamed tissues cleaved PAR2-derived peptides. These proteases and trypsin 4 increased [Ca(2+) ]i in PAR2-transfected but not in untransfected cells, and melagatran suppressed this activity. Melagatran or PAR2 deletion suppressed oedema and mechanical hypersensitivity induced by intraplantar formalin, bradykinin and PAR2-AP, but had no effect on capsaicin-induced pain.",
            "output": [
                "Do serine proteases and protease-activated receptor 2 mediate the proinflammatory and algesic actions of diverse stimulants?"
            ]
        },
        {
            "id": "task847-29d95004251c4f9c91427df291f305b1",
            "input": "The aim of this study is to examine the effects of taurine supplementation on homocysteine (Hcy) metabolism and liver injury in rats fed a choline-deficient diet.', 'Thirty rats were divided into three groups (n=10), to receive one of the following diets for 4 weeks: control diet (C), choline-deficient diet (CDD), or choline-deficient diet supplemented with taurine (CDDT). The CDD and the CDDT consisted of AIN-93 without the recommended choline content of 2.5%, and the CDDT was supplemented by the addition of 2.5% taurine.', 'Four weeks of ingesting a CDD resulted in a significant increase in plasma Hcy (50%) as well as a decrease in liver S-adenosylmethionine (SAM) concentration and S-adenosylmethionine/S-adenosylhomocysteine ratio. No changes were found in plasma methionine and cysteine plasma levels compared to control group. Four weeks of ingesting a CDD also caused a significant (P<0.05) increase in hepatic total fat, hepatic malondialdehyde (MDA), and plasma alanine aminotransferase (ALT) levels. In addition, reduced hepatic glutathione (GSH) levels and reduced/oxidized glutathione ratios (GSH/GSSG) were found in rats fed a CDD compared to controls. Taurine supplementation of the CDD normalized genes involved in the remethylation pathway, BHMT and CHDH, which were impaired by CDD alone. However, taurine supplementation failed to prevent CDD-induced Hcy metabolism disturbances and hepatic injury. Also, taurine added to CDD caused decreased expression of PEMT, CHKa, and CHKb, key genes involved in phosphatidylcholine (PC) synthesis and liver fat accumulation.",
            "output": [
                "Does taurine supplementation decrease homocysteine levels and liver injury induced by a choline-deficient diet?"
            ]
        },
        {
            "id": "task847-408b77e4b6904662a1615a47284073a8",
            "input": "Hypertension is a risk factor for atrial fibrillation. Activation of the renin-angiotensin-system seems to be involved in atrial enlargement, with release of atrial and brain natriuretic peptides. The aim of this study was to evaluate the relationship between ambulatory blood pressure and levels of natriuretic peptides, with left atrial size in normotensives with idiopathic atrial fibrillation.', 'This was a cross-sectional study in patients with idiopathic atrial fibrillation. The following measurements were recorded during the course of the study: office and 24-h ambulatory blood pressure, atrial and brain natriuretic peptides, plasma renin, aldosterone, and angiotensin-converting enzyme.', 'Forty-eight patients (mean age 55 [10] years; 70.6% male) were included in the study. Mean office sitting blood pressure values were 132.49 (14.9)/80.96 (9.2) mmHg. Mean 24-h ambulatory systolic and diastolic blood pressure values were 121.10 (8.3)/72.11 (6.8) mmHg (daytime, 126.8 [9.7]/77.58 [7.9] mmHg; nighttime, 114.56 [11.6]/68.6 [8.8] mmHg). A clear trend towards increased left atrial size with higher ambulatory blood pressure values was noted, which was statistically significant for nighttime values (r=0.34; P=.020 for systolic and r=0.51; p=.0001 for diastolic). A significant correlation between atrial natriuretic peptide and nighttime systolic (r=0.297; P=.047) and diastolic (r=0.312; P=.037) blood pressure was observed. Significant correlations were also observed between left atrial size and atrial natriuretic peptide levels (r=0.577; p<.0001) and brain natriuretic peptide levels (r=0.379; P=.012).",
            "output": [
                "Is nighttime ambulatory blood pressure associated with atrial remodelling and neurohormonal activation in patients with idiopathic atrial fibrillation?"
            ]
        },
        {
            "id": "task847-172f6dbb2ca04c1f808a46376e952232",
            "input": "To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy.', 'Prospective longitudinal cohort study.', \"A level IV neonatal ICU in a freestanding children's hospital.\", 'Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period.', 'Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia.', 'Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 \u00b1 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (< 70), or died. Elevated serum S100B and neuron-specific enolase levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and socioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were 2.5 (95% CI, 1.3-4.8) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase, and for motor outcome, 2.6 (95% CI, 1.2-5.6) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase.",
            "output": [
                "Do biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*?"
            ]
        },
        {
            "id": "task847-882c4051beec462cad31fc98a9a430ab",
            "input": "To empirically derive the optimal measure of pharmacologic cardiovascular support in infants undergoing cardiac surgery with bypass and to assess the association between this score and clinical outcomes in a multi-institutional cohort.', 'Prospective, multi-institutional cohort study.', \"Cardiac ICUs at four academic children's hospitals participating in the Pediatric Cardiac Critical Care Consortium during the study period.\", 'Children younger than 1 year at the time of surgery treated postoperatively in the cardiac ICU.', 'None.', 'Three hundred ninety-one infants undergoing surgery with bypass were enrolled consecutively from November 2011 to April 2012. Hourly doses of all vasoactive agents were recorded for the first 48 hours after cardiac ICU admission. Multiple derivations of an inotropic score were tested, and maximum vasoactive-inotropic score in the first 24 hours was further analyzed for association with clinical outcomes. The primary composite \"poor outcome\" variable included at least one of mortality, mechanical circulatory support, cardiac arrest, renal replacement therapy, or neurologic injury. High vasoactive-inotropic score was empirically defined as more than or equal to 20. Multivariable logistic regression was performed controlling for center and patient characteristics. Patients with high vasoactive-inotropic score had significantly greater odds of a poor outcome (odds ratio, 6.5; 95% CI, 2.9-14.6), mortality (odds ratio, 13.2; 95% CI, 3.7-47.6), and prolonged time to first extubation and cardiac ICU length of stay compared with patients with low vasoactive-inotropic score. Stratified analyses by age (neonate vs infant) and surgical complexity (low vs high) showed similar associations with increased morbidity and mortality for patients with high vasoactive-inotropic score.",
            "output": [
                "Is vasoactive-inotropic score associated with outcome after infant cardiac surgery : an analysis from the Pediatric Cardiac Critical Care Consortium and Virtual PICU System Registries?"
            ]
        },
        {
            "id": "task847-bb864ee9ca88430b81f7843ec6df1abd",
            "input": "Existing data on perfusion imaging assumes the perihemorrhagic zone (PHZ) in patients with intracerebral hemorrhage (ICH) to be size steady. This study investigates the size of the perihemorrhagic zone (PHZ) in patients with lobar ICH in relation to hematoma volume during the course of treatment using perfusion CT (PCT).', 'The present analysis is based on a previously reported cohort of 20 patients undergoing surgical evacuation for lobar SICH, with pre- and early postoperative PCT scanning. Time to peak of the residue function (T max) was measured based on the 360\u00b0 cortical banding method and singular value decomposition. The size of PHZ was determined before and after treatment and correlated with hematoma volume.', 'Preoperative mean hematoma volume constituted 63.0 ml (interquartile ranges (IQR) 39.7-99.4 ml), which correlated significantly (r=0.563, p=0.010) with mean PHZ size (5.67 cm, IQR 5.44-8.17 cm). Following a surgical hematoma evacuation, mean hematoma volume was reduced to 2.5 ml IQR 0.0-9.5 ml, which also resulted in a significant reduction of PHZ size to 0.45 cm(IQR 0.0-1.36 cm; p<0.001). There was no association between postoperative hematoma volume and size of the PHZ.",
            "output": [
                "Does the extent of the perihemorrhagic perfusion zone correlate with hematoma volume in patients with lobar intracerebral hemorrhage?"
            ]
        },
        {
            "id": "task847-64afb979bfd04612afb86e09c3a2fc1c",
            "input": "Cullin1 is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex which ubiquitinates a broad range of proteins participating in biochemical events like cell-cycle progression, signal transduction, and transcription. Cullin1 is involved in the progression of several cancers, such as melanoma, breast cancer, and gastric cancer.', \"To investigate the role of Cullin1 in the development of non-small-cell lung cancer (NSCLC), we examined the expression of Cullin1 in 8-paired fresh NSCLC tissues. We then constructed immunohistochemistry (IHC) on 114 paraffin-embedded slices and evaluated the correlation between Cullin1 expression and clinicopathologic variables, as well as patients' overall survival.\", \"We found that Cullin1 was highly expressed in NSCLC tissues and significantly associated with NSCLC's histological differentiation (P=0.002), clinical stage (P=0.010) and Ki-67 (P=0.021). Furthermore, we showed a strong correlation between high Cullin1 expression and worse overall survival rates in NSCLC patients (P<0.001). Cox regression analysis revealed that Cullin1 expression was an independent prognostic factor to predict 5-year patient outcome in NSCLC cancer (P=0.033).",
            "output": [
                "Does high expression of Cullin1 indicate poor prognosis for NSCLC patients?"
            ]
        },
        {
            "id": "task847-963303461b8e4259a1953f0e5bdcb784",
            "input": "The influence of nanoencapsulation of mometasone furoate (MF) in poly(\u03b5-caprolactone) lipid-core nanocapsules (LNC) on its in vitro human skin permeation and penetration was evaluated.', 'Semisolid formulations were prepared by increasing the viscosity of LNC using a carbomer (Carbopol(\u00ae) Ultrez at 0.5% w/v). Two complementary techniques (the static Franz diffusion cell model and the Saarbr\u00fccken penetration model) were used to evaluate skin permeation/penetration.', 'The drug release rate was decreased by nanoencapsulation. The skin permeability of MF was controlled by the nanoencapsulation as well as by increasing the viscosity. Furthermore, the formulation containing the nanoencapsulated MF controlled the amount of drug reaching the deeper skin layers without changing its accumulation in the stratum corneum.",
            "output": [
                "Does nanoencapsulation in lipid-core nanocapsules control mometasone furoate skin permeability rate and its penetration to the deeper skin layers?"
            ]
        },
        {
            "id": "task847-b92b0dfd64434bb38e9cc6839e0792e3",
            "input": "Reducing central line-associated bloodstream infections (CLABSIs) poses a set of unique challenges in long-term acute care hospitals (LTACHS). Patients are often admitted to LTACHs with central lines in place from the previous hospitalization; thus, LTACHs lack control over insertion techniques and respective central line care and maintenance. This study aimed to demonstrate the impact of a methodical bathing approach with 2% chlorhexidine gluconate (CHG) cloths and a correlation with a reduced prevalence of CLABSIs in our LTACH population.', 'This retrospective observational quality initiative conducted in a 105-bed LTACH used plan-do-study-act methodology to assess the effects of a revised bathing approach using 2% CHG.', 'Statistical significance demonstrated a 65% reduction in CLABSI on the pilot unit after the 6-month initial trial. The results of the quality initiative were evaluated through the end of\\xa02012.",
            "output": [
                "Does quality improvement intervention reduce episodes of long-term acute care hospital central line-associated infections?"
            ]
        },
        {
            "id": "task847-4bd680dcd3e64000ab3792dee3934e26",
            "input": "Large volumes of information in the OR are ignored by surgeons when the amount outpaces human mental processing abilities. We developed an augmented reality (AR) system for dental implant surgery that acts as an automatic information filter, selectively displaying only relevant information. The purpose is to reduce information overflow and offer intuitive image guidance. The system was evaluated in a pig cadaver experiment.', 'Information filtering is implemented via rule-based situation interpretation with description logics. The interpretation is based on intraoperative distances measurement between anatomical structures and the dental drill with optical tracking. For AR, a head-mounted display is used, which was calibrated with a novel method based on SPAAM. To adapt to surgeon specific preferences, we offer two alternative display formats: one with static and another with contact analog AR.', 'The system made the surgery easier and showed ergonomical benefits, as assessed by a questionnaire. All relevant phases were recognized reliably. The new calibration showed significant improvements, while the deviation of the realized implants was <2.5 mm.",
            "output": [
                "Do a system for context-aware intraoperative augmented reality in dental implant surgery?"
            ]
        },
        {
            "id": "task847-705a59ebd357457aaf0736535ee03f46",
            "input": "We investigated the function of major superoxide-generating enzymes after remote ischemic preconditioning (IPC) and hepatic ischemia-reperfusion (IR), with the specific aim of assessing the importance of the most relevant NADPH oxidase (NOX) isoforms, NOX2 and NOX4, in the mechanism of action.', '60-min partial liver ischemia was induced in Sprague-Dawley rats in the presence or absence of remote IPC (2 \u00d7 10-min limb IR), and hepatic microcirculatory variables were determined through intravital video microscopy and lightguide spectrophotometry during reperfusion. Inflammatory enzyme activities (myeloperoxidase (MPO) and xanthine oxidoreductase (XOR)), cytokine production (TNF-\u03b1 and HMGB-1), liver necroenzyme levels (AST, ALT and LDH) and NOX2 and NOX4 protein expression changes (Western blot analysis) were assayed biochemically.', 'In this setting, remote IPC significantly decreased the IR-induced hepatic NOX2 expression, but the NOX4 expression remained unchanged. The remote IPC provided significant, but incomplete protection against the leukocyte-endothelial cell interactions and flow deterioration. Hepatocellular damage (AST, ALT and LDH release), cytokine levels, and XOR and MPO activities also diminished.",
            "output": [
                "Does remote ischemic preconditioning differentially affect NADPH oxidase isoforms during hepatic ischemia-reperfusion?"
            ]
        },
        {
            "id": "task847-e44577cd179745178b2c1e2e2f6cc245",
            "input": "THE AIM OF THE STUDY WAS: Is primary Arterio-venous fistula the vascular access of choice for adequate dialysis and better patient outcome in end stage renal disease.', 'The present study was done in the department of cardiovascular and thoracic surgery at Sher-i-Kashmir institute of medical sciences, Soura, Srinagar Kashmir. Native Arterio-Venous (AV) fistulas were made in the patients with end stage renal disease for performing hemodialysis. They were followed for patency and adequacy of blood flow during hemodialysis. All the patients were operated under local anesthesia.', 'The results showed that 77% of the AV fistulas based on radial artery with side-to-side anastomosis and 80% of those with end-to-side anastomosis were functionally patent after one year. After two years, the patency rate in side-to-side and end-to-side anastomosis was 50% and 55%, respectively. In addition, the patency rate was 90% in brachial artery based AV fistula with end-to-side anastomosis, whether done primarily or secondarily, at the end of one year. However, a rapid decline was observed in the patency rate during the third year in both radial artery based and brachial artery based AV fistulas.",
            "output": [
                "Is native arterio-venous fistula the vascular access of choice for hemodialysis in end stage renal disease?"
            ]
        },
        {
            "id": "task847-27ee70e956ac4ac1997a8f74ffa16515",
            "input": "This study was conducted to determine if there was an increase in the urinary excretion of fluoride, after the use of fluoride mouth rinses in children.', 'The sample consisted of 58 children aged 5-8 years, randomly selected, residents in non-fluoridated water areas. Urine samples were collected prior to mouthwash and also 2 hours after use. The control sample, which received no treatment, consisted of 16 children of equivalent age and from the same community. Urinary excretion of fluoride was analysed by determining the pH, creatinine, F- ion and fluoride (mg)/creatinine (g) (F/Cr) ratio in urine. Results In the studied sample, the mean F/Cr ratio before fluoride mouth rinse was 0.26 mg/g and it rose to 1.58 mg/g 2 hours after mouth rinse. This difference of 1.33 mg/g was statistically highly significant (p<.001). In the control group no significant changes occurred. The average 2 hours afterward F/Cr ratios were 0.29 and 0.27 respectively (p=0.426).",
            "output": [
                "Does renal excretion of fluoride after fluoride mouth rinse in children?"
            ]
        },
        {
            "id": "task847-abd7168df7d44d38b60b2da83950a82a",
            "input": "Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient.', 'Archival tissue samples derived from patients with pathologically confirmed central nervous system inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy were analyzed immunohistochemically. The inclusion criteria consisted of the presence of early active demyelinating lesions--required for immunopattern classification--obtained from the same patient at 2 or more time points.', 'Among 1,321 surgical biopsies consistent with MS, 22 cases met the study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy.",
            "output": [
                "Does pathologic heterogeneity persist in early active multiple sclerosis lesions?"
            ]
        },
        {
            "id": "task847-f367a28347dc4ee9ba8165ad8f1b9951",
            "input": "We aimed to investigate the relationship between plasma and CSF progranulin (PGRN) levels.', 'Plasma and CSF PGRN were measured in a cohort of 345 subjects from the Mayo Clinic Study of Aging by ELISA. Single nucleotide polymorphism genotyping was performed using TaqMan assays. Associations between PGRN and sex, age at sample collection, diagnosis, single nucleotide polymorphism genotypes (GRN, SORT1, and APOE), and Pittsburgh compound B score were explored separately in CSF and plasma using single variable linear regression models. Pearson partial correlation coefficient was used to estimate the correlation of PGRN in CSF and plasma.', 'Plasma (p = 0.0031) and CSF (p = 0.0044) PGRN significantly increased with age, whereas plasma PGRN levels were 7% lower (p = 0.0025) and CSF PGRN levels 5% higher (p = 0.0024) in male compared with female participants. Correcting for age and sex, higher plasma PGRN was associated with higher CSF PGRN (partial r = 0.17, p = 0.004). In plasma, both rs5848 (GRN; p = 0.002) and rs646776 (SORT1; p = 3.56E-7) were associated with PGRN, while only rs5848 showed highly significant association in CSF (p = 5.59E-14). Age, sex, rs5848 genotype, and plasma PGRN together accounted for only 18% of the variability observed in CSF PGRN.",
            "output": [
                "Are progranulin protein levels differently regulated in plasma and CSF?"
            ]
        },
        {
            "id": "task847-6284f70565a04774b4064b20a5d15146",
            "input": "There is a higher likelihood of crashes and fatalities when an adolescent drives with peer passengers, especially for male drivers and male passengers. Simulated driving of male adolescent drivers with male peer passengers was studied to examine passenger influences on distraction and inattention.', \"Male adolescents drove in a high-fidelity driving simulator with a male confederate who posed either as a risk-accepting passenger or as a risk-averse passenger. Drivers' eye movements were recorded. The visual scanning behavior of the drivers was compared when driving alone with when driving with a passenger and when driving with a risk-accepting passenger with a risk-averse passenger.\", \"The visual scanning of a driver significantly narrowed horizontally and vertically when driving with a peer passenger. There were no significant differences in the times the drivers' eyes were off the forward roadway when driving with a passenger versus when driving alone. Some significant correlations were found between personality characteristics and the outcome measures.",
            "output": [
                "Does peer passenger influence on male adolescent drivers ' visual scanning behavior during simulated driving?"
            ]
        },
        {
            "id": "task847-74b3923fb5a94682be6163896adea37f",
            "input": "HAGE protein is a known immunogenic cancer-specific antigen.', 'The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated.', 'Eight percent of patients with EP-BC exhibited high HAGE expression (HAGE+) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGE+expression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+residual disease (P=0.0003).",
            "output": [
                "Is hAGE ( DDX43 ) a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer?"
            ]
        },
        {
            "id": "task847-4406a66926604669a6812618c9d31168",
            "input": "Inflammatory reaction in blood-spinal cord barrier (BSCB) plays a crucial role in ischemia/reperfusion (I/R) injury. It has been shown that microglia could be activated through Toll-like receptors (TLRs). Therefore, we hypothesize that TLR4 is involved in the microglial activation and BSCB disruption after I/R.', \"To verify our hypothesis, we analyzed the behavioral data, changes of BSCB permeability, as well as expressions of microglial marker Iba-1 and TLR4 in spinal cord I/R model induced by 14\\xa0min aortic occlusion. Double immunostaining reveals that after I/R, Iba-1 immunoreactivity increased gradually 12\\xa0h after reperfusion and maintained at a such level throughout 36\\xa0h. Such increasing pattern of Iba-1 expression is consistent with the increases in Evan's Blue (EB) extravasation, spinal water content and mechanical allodynia demonstrated by lowed withdrawal threshold to Von Frey filaments. Moreover, double immunostaining suggested that TLR4 was highly expressed in microglia. Intrathecal infusion of minocycline and TAK-242 (TLR4 inhibitor) treatment attenuated I/R-induced allodynia and BSCB leakage. In contrast, LPS induced TLR4 expression aggregated above-mentioned injuries. Furthermore, the nuclear factor-kappa B (NF-\u03baB) activity has a similar profile as TLR4 activity. It is consisted with the results of NF-\u03baB mRNA and protein expression changes and activation of downstream cytokine, IL-1\u03b2. Expectedly, intrathecal infusion of pyrrolidine dithiocarbamate (PDTC), a NF-\u03baB inhibitor, showed similar protective effects as minocycline and TAK-242. In addition, our data show that TLR4 closely involved in I/R-induced inflammatory damage induced neuronal apoptosis. Significantly, neutralizing TLR4 function largely reduced neuronal apoptosis determined by NeuN immunoreactivity in ventral gray matter and increased percentage of double-label cells with cleaved caspase3, whereas LPS reversed these effects. Similarly, inhibitions of microglia and NF-\u03baB with minocycline or PDTC treatment accordingly perform the same protective effects on I/R injury.",
            "output": [
                "Does intrathecal antagonism of microglial TLR4 reduce inflammatory damage to blood-spinal cord barrier following ischemia/reperfusion injury in rats?"
            ]
        },
        {
            "id": "task847-3c5aa2662aac420997d905182a01e3ab",
            "input": "While the incidence of inflammatory bowel disease (IBD) among African-Americans (AAs) is increasing, there is limited understanding of phenotypic differences and outcomes by race.', 'To describe disease characteristics of AA patients compared to Caucasian (Ca) patients in a tertiary care population.', \"We performed a cross-sectional review of the IBD registry at the University of Chicago from January 2008 to January 2013. Data regarding race, phenotype, disease onset, disease duration, medical therapy, and surgical treatment were abstracted from the database, then compared via Pearson's chi-square analysis, Kruskal-Wallis analysis, and logistic regression with a significance level of p < 0.05.\", \"A total of 1,235 patients with Crohn's disease (CD) and 541 patients with ulcerative colitis (UC) included 108 AA CD patients and 28 AA UC patients. AA CD patients had an increased rate of IBD-related arthralgias (36.5 vs. 23.9 %, p < 0.01) and surgery (p < 0.01), less ileal involvement (57.8 vs. 71.0 %, p < 0.01), and no differences for other extraintestinal manifestations or disease locations compared to Ca CD patients. AA UC patients were older at diagnosis, had an increased rate of arthralgias (28.6 vs. 14.6 %, p = 0.047) and ankylosing spondylitis/sacroiliitis (7.1 vs. 1.6 %, p = 0.035), with no differences for disease extent or rate of IBD-related surgeries compared to Ca UC patients. There were no differences in medication usage by race for CD and UC patients.",
            "output": [
                "Does clinical presentation and disease course of inflammatory bowel disease differ by race in a large tertiary care hospital?"
            ]
        },
        {
            "id": "task847-03293eba7f1a4cd097a63d0b9dd1c676",
            "input": "Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis, as a majority of patients present with advanced disease. Current adjuvant strategies for metastatic patients include mitotane or other cytotoxic agents and carry a significant morbidity as well as a low (<10 %) 5-year survival. Withanolides, including withaferin A, are novel chemotherapeutic agents with potent targeted effects in medullary thyroid cancer and a number of solid malignancies with low toxicity in vivo. We hypothesize that novel naturally derived withanolides will have potent targeted anti-cancer activity against ACCs.', 'In vitro cell viability of ACC cell lines (Y1 and SW13) was measured using MTS cell proliferation assay. Cell cycle and apoptotic analysis studied using annexin V/propidium iodide staining on flow cytometry (FC) and targeted molecular mechanisms of withanolide cytotoxicity were assessed using standard Western blot analysis.', 'All the withanolides potently reduced ACC cell viability on MTS assay with 7- to 185-fold higher selectivity than normal fibroblasts. Cell cycle analysis demonstrated a shift in cell cycle arrest from G1/G0 to G2/M with induction of apoptosis at nanomolar concentrations of withanolides. Unlike current ACC therapeutics, withanolides modulated expression of several key oncogenic pathway proteins in ACCs by Western blot, including Jagged 1, MAPK, and Akt/mTOR pathway proteins in a dose-dependent manner after 24 h drug treatment of SW13 cells.",
            "output": [
                "Are withanolides potent novel targeted therapeutic agents against adrenocortical carcinomas?"
            ]
        },
        {
            "id": "task847-28b2bbd445124b95ae325601bfd79abf",
            "input": "Mesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti-inflammatory therapy may favor airway remodeling and therefore be detrimental.', 'Adipose tissue-derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite-instilled animals receiving intravenous vehicle or phosphate-buffered saline-instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72 h after injection or after 2 weeks of additional intranasal challenge.', 'The mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T-helper-1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues.",
            "output": [
                "Do mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma?"
            ]
        },
        {
            "id": "task847-d5cd03f7fbbd4183a37f58fa85743d56",
            "input": "Tyrosine kinase inhibitors (TKIs) have achieved remarkable clinical results in medullary thyroid carcinoma (MTC) patients. However, the considerable variability in patient response to treatment with TKIs remains largely unexplained. There is evidence that it could be due, at least in part, to alterations in genes associated with the disease via their effect on the expression of TKI targets. The objective of this study was to evaluate the influence of RAS mutations on the expression levels in MTC tumors of eight key TKI target proteins.', 'We assessed by immunohistochemistry the expression of EGFR, KIT, MET, PDGFRB, VEGF, VEGFR1, VEGFR2, and VEGFR3 in a series of 84 primary MTC tumors that had previously been molecularly characterized, including 14 RAS-positive, 18 RET(M918T)-positive, and 24 RET(C634)-positive tumors, as well as 15 wild-type tumors with no mutations in the RET or RAS genes.', 'In contrast to RET-positive tumors, RAS-positive tumors expressed neither PDGFRB nor MET (p=0.0060 and 0.047, respectively). Similarly, fewer RAS-positive than RET-related tumors expressed VEGFR3 (p=0.00062). Finally, wild-type tumors expressed VEGF more often than both RAS- and RET-positive tumors (p=0.0082 and 0.011, respectively).",
            "output": [
                "Is vEGF , VEGFR3 , and PDGFRB protein expression influenced by RAS mutations in medullary thyroid carcinoma?"
            ]
        },
        {
            "id": "task847-5c64ec2e1f104b3e8c60d3e3d93c0adb",
            "input": "Adverse drug events (ADE) contribute significantly to hospital admissions. Prospective New Zealand data are scant, and the ability of clinical coding to identify ADE associated admissions is uncertain. Outcomes after cessation of causative medications are unknown.', 'To assess the frequency, nature and causality of ADE associated with acute admissions to General Medicine at Christchurch Hospital.', 'Prospective observational study of patients admitted to our medical team over 20 weeks.', 'Of 336 admissions, 96 (28.6%) were ADE related. Sixty-five (19.3%) were caused by an ADE, and 31 (9.2%) were contributed to by an ADE. The mean age of non-ADE patients was 64.3 years (range 16-91), which was similar to the mean age of ADE patients (65.9 years; 21-92). However, if intentional overdoses and recreational drug use were excluded, ADE patients were significantly older at 72.4 years (21-92) (P = 0.0007). ADE patients took more regular medications on admission (mean 6.6, range 0-22) than non-ADE patients (mean 5.0, 0-18), (P = 0.003). The average length of stay was similar. The commonest medications implicated were vasodilators, psychotropics and diuretics. The most common adverse effects were postural hypotension and/or vasovagal syncope (29% of ADE), intentional overdoses and recreational drug use (15%) and acute renal failure and/or clinical dehydration (10%). Seventy-six patients had culprit medications stopped or reduced, and this potentially contributed to six readmissions. Coding identified 61% of ADE associated admissions.",
            "output": [
                "Are adverse drug events a major cause of acute medical admission?"
            ]
        },
        {
            "id": "task847-9d45bb4a7c31423cb312a918ef1ff860",
            "input": "Three-dimensional (3D) surface matching is a novel method to administer deep inspiration breath-hold (DIBH) radiation therapy for left-sided breast cancer to reduce cardiac exposure. We analyzed port (x-ray) films to assess patient setup accuracy and treatment times to assess the practical workflow of this system.', 'The data from 50 left-sided breast cancer patients treated with DIBH were studied. AlignRT (London, UK) was used. The distance between the field edge and the anterior pericardial shadow as seen on the routine port films (dPORT), and the corresponding distance seen on the digitally reconstructed radiographs (DRR) from the planning (dDRR) were compared as a quantitative measure of setup accuracy. Variations of dPORT - dDRR over the treatment course were assessed. In a subset of 21 patients treated with tangential beams alone, the daily treatment durations were analyzed to assess the practical workflow of this system.', 'Considering all 50 patients, the mean absolute systematic uncertainty between dPORT and dDRR was 0.20 cm (range, 0 to 1.22 cm), the mean systematic uncertainty was -0.07 cm (range, -1.22 to 0.67 cm), and their mean random uncertainty was 0.19 cm (range, 0 to 0.84 cm). There was no significant change in dPORT - dDRR during the course of treatment. The mean patient treatment duration for the 21 patients studied was 11 minutes 48 seconds. On intrapatient assessments, 15/21 had nonsignificant trends toward reduced treatment durations during their course of therapy. On interpatient comparisons, the mean treatment times declined as we gained more experience with this technique.",
            "output": [
                "Do clinical experience with 3-dimensional surface matching-based deep inspiration breath hold for left-sided breast cancer radiation therapy?"
            ]
        },
        {
            "id": "task847-304faa4f37af48b2a8a06e1b0e7a3ed9",
            "input": "To evaluate the impact of elevated serum \u03944A levels on the hormonal and metabolic features of the different phenotypes of PCOS.', '1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined.', 'In PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), \u03944A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/\u03944A ratio. In the milder phenotype III, a positive correlation between \u03944A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased \u03944A and T/\u03944A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II.",
            "output": [
                "Is elevated serum androstenedione associated with a more severe phenotype in women with polycystic ovary syndrome ( PCOS )?"
            ]
        },
        {
            "id": "task847-5f1078405910465a8e8ab69f588e890d",
            "input": "To investigate the effect of glycyrrhizin (Gly) on human neutrophil elastase (HNE)- induced mucin (MUC) 5AC overproduction in human bronchial epithelial cells (16HBE), and the potential signaling pathway involved in this process.', 'The cultured cells were divided into 3 groups: a control group, cultured in serum-free DMEM medium; an HNE group, pretreated with HNE alone; and a Gly group, incubated with HNE and Gly. After stimulation with a variety of Gly concentrations, the cytotoxicity was assessed by methyl thiazolyl tetrazolium method. The mRNA expressions of p38, nuclear factor \u03baB (NF-\u03baB) p65, inhibitory \u03baB\u03b1 (I\u03baB\u03b1) and MUC5AC were detected by real-time PCR. The phosphorylation levels of p38 (p-p38), NF-\u03baB p65 (p-NF-\u03baB p65) and I\u03baB\u03b1 (p-I\u03baB\u03b1) were measured by Western blot while the levels of MUC5AC protein were analyzed by emzyme-linked immunosorbent assay and immunofluorescence.', 'Compared with the control group, the expression levels of MUC5AC mRNA and protein in the HNE group were both significantly increased. There was a significant increase in p-p38 and p-NF-\u03baB p65, while the production of I\u03baB\u03b1 was much lower than that in the control group. Gly significantly inhibited the increase of MUC5AC, p38 and NF-\u03baB p65, but increased the activity of I\u03baB\u03b1.",
            "output": [
                "Does [ Glycyrrhizin inhibit human neutrophil elastase-induced mucin 5AC overproduction in human bronchial epithelial cells ]?"
            ]
        },
        {
            "id": "task847-87b3029842624157a4ffb665de034bca",
            "input": "Laparoscopic ventral hernia repair (LVHR) is associated with shorter hospitalization and lower complication rates compared to open ventral hernia repair. We sought to determine if hernia-related factors, such as defect size and re-operative status correlate with postoperative complications, operative times and length of stay (LOS).', 'The study is a retrospective review of 30-day perioperative outcomes following LVHR in 91 patients who underwent surgery at a single institution from August 2009 through June 2012. A single surgeon performed all procedures.', 'Indications for surgery were recurrent incisional hernia in 33\\xa0% of patients and primary incisional or ventral abdominal hernias in the rest. Coated polyester mesh with an average size of 348\\xa0cm(2) (\u00b1214; range 113-1,036) was used. Mean operative time was 132\\xa0min (\u00b166.1; range 53-412). The mean LOS was 4.0\\xa0days (\u00b13.5; range 1-22). Complications occurred in 13 patients for overall morbidity of 16.5\\xa0% and no mortality. There was one recurrence in 30\\xa0days (1.1\\xa0%). Patients who had a surgery >120\\xa0min or a LOS >1\\xa0day were statistically more likely to have multiple hernias, larger defect sizes (>40\\xa0cm(2)), larger mesh sizes (>300\\xa0cm(2)) or a history of recurrent hernia (P\\xa0<\\xa00.05). No other clinical or demographic variable evaluated in this study correlated with operative time or LOS.",
            "output": [
                "Does laparoscopic hernia complexity predict operative time and length of stay?"
            ]
        },
        {
            "id": "task847-530d1b658856422492c3dd9ce9c358a4",
            "input": "Collagen is the major structural protein of human dentin. Degradation of collagen by bacterial enzymes can facilitate microbial penetration, compromise structural/interfacial integrity, and lower resistance to fracture of dentin. We evaluated the ability of photodynamic therapy (PDT), bioactive chitosan nanoparticles (CSnp), or PDT in combination with CSnp to inhibit bacterial collagenase-mediated degradation of collagen.', 'Rat type 1 fibrillar collagen matrices were untreated or treated with 2.5% glutaraldehyde (GD), 2.5% GD followed by 1% CSnp, 1% CSnp, PDT (rose bengal activated with 540 nm light at 40 J/cm(2)), or 1% CSnp followed by PDT. Samples, except those used as untreated controls, were exposed to Clostridium histolyticum collagenase (125 CDU/mL) for 24 hours. The soluble digestion products were assessed by hydroxyproline assay, and the remaining adherent collagen was quantified by picrosirius red staining. Fourier transform infrared spectroscopy, immunoblotting, and scanning electron microscopy were used to study the interaction between CSnp/PDT with type 1 collagen. The data were analyzed by 1-way analysis of variance and post hoc Tukey test.', 'As assessed by hydroxyproline release into the medium, collagen treated with CSnp, PDT, or a combination of CSnp and PDT exhibited less degradation than untreated controls (3.6-fold, 1.7-fold, and 7.9-fold reduction, respectively; P < .05). Compared with all other treatments, GD-treated collagen was the most resistant to collagenolytic degradation (239.6-fold reduction, P < .05). The abundance of post-treatment residual collagen, as measured by picrosirius red staining, was inversely related to the extent of collagen degradation. Analysis of collagen cross-links with Fourier transform infrared spectroscopy showed that PDT or GD treatments enhanced collagen cross-linking. Immunoblotting of sedimented CSnp indicated that CSnp and collagenase bound with low affinity. However, CSnp-bound collagenase showed a significant reduction in collagenolytic activity compared with controls (P < .05).",
            "output": [
                "Do bioactive chitosan nanoparticles and photodynamic therapy inhibit collagen degradation in vitro?"
            ]
        },
        {
            "id": "task847-8f5c76d5b2ef4b1b9784ad5de0fc7260",
            "input": "Classical conditioning of the eyeblink reflex is a simple form of motor learning which depends on the integrity of the cerebellum. Acquisition of conditioned eyeblink responses is markedly reduced in patients with cerebellar disorders. Noninvasive transcranial direct current stimulation (tDCS) has been reported to modify the excitability of the cerebellar cortex.', 'The aim of the study was to assess whether acquisition of conditioned eyeblink responses (CR) is altered by cerebellar tDCS.', 'A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 30 healthy subjects (18 female, 12 male, mean age 23.4 \u00b1 1.9 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. tDCS (2 mA intensity, ramp like onset) was applied over the right cerebellar hemisphere ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 10) using anodal, cathodal or sham stimulation. The investigator as well as the participants was blinded to the stimulation modality.', 'CR acquisition was significantly enhanced by anodal tDCS (mean total CR incidence 73.4 \u00b1 25.2%) and significantly reduced by cathodal stimulation (12.6 \u00b1 17.2%) compared to sham stimulation (43.8 \u00b1 24.1%). During anodal tDCS CR onset occurred significantly earlier, that is mean onset of responses was shifted closer to CS onset.",
            "output": [
                "Is acquisition of conditioned eyeblink responses modulated by cerebellar tDCS?"
            ]
        },
        {
            "id": "task847-a8111611f8c9445a9e42e5b963f0fa62",
            "input": "To examine relationships among demographic variables, healthcare system distrust, lung cancer stigma, smoking status, and timing of medical help-seeking behavior in individuals with symptoms suggestive of lung cancer after controlling for ethnicity, socioeconomic status, and social desirability.', 'Descriptive, cross-sectional, correlational study.', 'Outpatient oncology clinics in Louisville, KY.', '94 patients diagnosed in the past three weeks to six years with all stages of lung cancer.', 'Self-report, written survey packets were administered in person followed by a semistructured interview to assess symptoms and timing characteristics of practice-identified patients with lung cancer.', 'Timing of medical help-seeking behavior, healthcare system distrust, lung cancer stigma, and smoking status.', 'Lung cancer stigma was independently associated with timing of medical help-seeking behavior in patients with lung cancer. Healthcare system distrust and smoking status were not independently associated with timing of medical help-seeking behavior.",
            "output": [
                "Does lung cancer stigma predict timing of medical help-seeking behavior?"
            ]
        },
        {
            "id": "task847-bd585d4278b843fe9d4a02fcb852247a",
            "input": "This study is to investigate if polymerase I and transcript release factor (PTRF) acts as a modulator in glioblastoma (GBM) chemoresistance.', 'Multidrug resistant (MDR) GBM cell line U251AR was established by exposing the U251 cell line to imatinib. The 2D-DIGE and MALDI-TOF/TOF-MS were performed on U251 and U251AR cell lines to screen MDR-related proteins. The expression of PTRF was determined by Western blot and quantitative RT-PCR analyses.', 'When compared with the parental U251 cells, expression of 21 proteins was significantly altered in U251AR cells. Among the 21 differentially expressed proteins, the expression of PTRF was up-regulated by 2.14 folds in U251AR cells when compared with that in the parental U251 cells. Knockdown of PTRF in GBM cell lines significantly increased chemosensitivity of cells to various chemical drugs and decreased the expression levels of caveolin1, a major structural component of caveolae. Expression levels of PTRF and caveolin1 were significantly up-regulated in the relapsed GBM patients. The mRNA level of PTRF and caveolin1 showed a positive correlation in the same GBM specimens.",
            "output": [
                "Does polymerase I and transcript release factor act as an essential modulator of glioblastoma chemoresistance?"
            ]
        },
        {
            "id": "task847-e02cc0023f9e4ab490c1f930e5ea5370",
            "input": "Immune dysregulation can affect insulin resistance (IR) and \u03b2-cell function and hence contribute to development of type 2 diabetes mellitus (T2DM). The complement system, as a regulator of immune and inflammatory homeostasis, may be a relevant contributor therein. However, longitudinal studies focusing on complement as a determinant of T2DM and IR are scarce. Therefore, we prospectively investigated the association of plasma complement factor 3 (C3) with (estimates of) IR in muscle, liver, and adipocytes, as well as with glucose tolerance, including incident T2DM.', 'Fasting C3, nonesterified fatty acids, glucose, and insulin (the latter two during oral glucose tolerance tests) were measured at baseline (n = 545) and after 7 years of follow-up (n = 394) in a prospective cohort study.', 'Over the 7-year period, C3 levels (per 0.1 g/L) were longitudinally associated with higher homeostasis model assessment of IR (HOMA2-IR; \u03b2 = 15.2% [95% CI 12.9-17.6]), hepatic IR (\u03b2 = 6.1% [95% CI 4.7-7.4]), adipocyte IR (\u03b2 = 16.0% [95% CI 13.0-19.1]), fasting glucose (\u03b2 = 1.8% [95% CI 1.2-2.4]), 2-h glucose (\u03b2 = 5.2% [95% CI 3.7-6.7]), and area under the curve for glucose (\u03b2 = 3.6% [95% CI 2.7-4.6]). In addition, greater changes in C3 (per 0.1 g/L) were associated with greater changes in HOMA2-IR (\u03b2 = 0.08 [95% CI 0.02-0.15]) and greater changes in hepatic IR (\u03b2 = 0.87 [95% CI 0.12-1.61]) over 7 years, but not glucose tolerance. Moreover, baseline C3 was associated with the 7-year incidence of T2DM (odds ratio 1.5 [95% CI 1.1-2.0]).",
            "output": [
                "Is complement factor 3 associated with insulin resistance and with incident type 2 diabetes over a 7-year follow-up period : the CODAM Study?"
            ]
        },
        {
            "id": "task847-8dc176c9a394423882ed83bf6b19055e",
            "input": "Stilbenes are plant secondary metabolites that have shown promising and varied biological activities. Stilbenes are presently actively studied for the exploitation of this primary raw material resource, involving the concept of biorefining. Methods for the rapid discovery of new and known stilbene structures from various plant sources are thus keenly sought.', 'To establish a simple and rapid technique of off-line HPLC with a diode-array detector (DAD) and NMR for the unambiguous structural elucidation of stilbene structures in the root bark of Norway spruce [Picea abies (L.) Karst.].', 'The stilbene containing fraction was extracted from the plant bark with an ethanol:water mixture (95:5, v/v) preceded by defatting of hydrophobic compounds with n-hexane using the accelerated solvent extraction technique. A portion of the ethanol-water soluble extract was hydrolysed with \u03b2-glucosidase to prepare stilbene aglycones. The extracts were further purified and enriched using a polymeric adsorbent. Stilbene-enriched extracts were directly characterised by off-line HPLC/DAD-NMR in conjunction with HPLC/DAD and HPLC/DAD with electrospray ionisation MS(n).', 'Trans-isorhapontin and trans-astringin were identified as the major, and trans-piceid as a minor, stilbene glucosides of the bark of roots of Picea abies. Not only stilbene glucosides but also the corresponding stilbene aglycones, such as trans-resveratrol, trans-piceatannol and trans-isorhapontigenin, were rapidly identified from the hydrolysed extract. The acquired heteronuclear single-quantum coherence and heteronuclear multiple bond correlation spectra were used to assign the complete carbon NMR chemical shifts of trans-isorhapontin and trans-astringin without the need of acquiring a (13)C-NMR spectrum.",
            "output": [
                "Do rapid chemical characterisation of stilbenes in the root bark of Norway spruce by off-line HPLC/DAD-NMR?"
            ]
        },
        {
            "id": "task847-15feb6fbb0564b44a343e08f91535f1f",
            "input": "Adolescent depression is more common in lower socio-economic groups. Whether this pattern has changed over time, is not known.We examined the prevalence of self-reported depression and its changes in socio-economic groups from 2000 to 2011 among Finnish adolescents.', \"Data were based on classroom surveys every second year from 2000-2001 to 2010-2011 using nationwide samples of 14-16-year old Finns (n\\u2009=\\u2009618,084). Data were collected using self-administered questionnaires including questions on health, health behaviours, and school experiences. Depression was measured with a Finnish modification of the 13-item Beck Depression Inventory, and divided into no, mild, moderate and severe depression. The association between depression and the social background (parents' education and employment) over time was studied using a multinomial regression analysis.\", 'The prevalence of self-reported severe depression slightly increased from 2000-2001 to 2010-2011 in girls. In boys a slight increase was observed when adjusting for background variables. The differences in the prevalence of depression between the social background groups persisted over the entire study period. In both sexes, severe depression nearly doubled among those adolescents whose parents were unemployed and had a low education level; among boys, the prevalence was 6.5% in 2000-2001 and 12.8% in 2010-2011, and among girls 6.4% and 11.4% respectively.",
            "output": [
                "Is self-reported depression increasing among socio-economically disadvantaged adolescents - repeated cross-sectional surveys from Finland from 2000 to 2011?"
            ]
        },
        {
            "id": "task847-93886d64c80b4c2c8f0b282b47353a59",
            "input": "We describe a three-year experience with patients with dementia.', 'clinical, cognitive and functional evaluation was performed by a multidisciplinary team for persons above 60 years. Mortality was assessed after three years.', \"Mini-Mental State Examination (MMSE) (n=2,074) was 15.7 (8.4). Male patients MMSE (n=758) was 15.6 (8.3) and female's (n=1315) was 15.8 (8.3). Instrumental Activities of Daily Living Scale (n=2023) was 16.5 (7.6); females (n=1277) was 16.9 (7.2) and males (n=745) was 15.7(8.2). From these patients, 12.6% (n=209) died within three years. Baseline cognition of patients still alive was higher (p<0.001) than MMSE of those who died [MMSE=16.3 (8.1) vs. 10.6 (7.6)]. Mortality rate decreased 6% (IR=0.94) for each additional point on MMSE. Higher functional status decreases the mortality rate approximately 11% (IR=0.89) independently of age, gender, and education.",
            "output": [
                "Is lower mortality rate in people with dementia associated with better cognitive and functional performance in an outpatient cohort?"
            ]
        },
        {
            "id": "task847-708223c72e414e5ca6b0fce7909d2887",
            "input": "MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis.', 'We conducted a case-control study to analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV carriers. Then, we evaluated the correlation between the polymorphism and hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or advanced stage without surgical treatment.', 'The variant genotypes of rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted odds ratio (OR)\\u200a=\\u200a0.90, 95% confidence intervals (CI)\\u200a=\\u200a0.81-1.00, P\\u200a=\\u200a0.047]. Moreover, HCC patients with the variant genotypes were associated with a better survival [Adjusted hazard ratio (HR)\\u200a=\\u200a0.70, 95% CIs\\u200a=\\u200a0.59-0.83, P<0.0001 in an additive genetic model]. The reporter gene assay showed that the variant G allele of rs1076064 exerted higher promoter activity than the A allele.",
            "output": [
                "Is a genetic variant in primary miR-378 associated with risk and prognosis of hepatocellular carcinoma in a Chinese population?"
            ]
        },
        {
            "id": "task847-cb6c22afd2ba425f84465d137e10ea71",
            "input": "While glucocorticoids and the liganded glucocorticoid receptor (GR) have a well-established role in the maintenance of differentiation and suppression of apoptosis in breast tissue, the involvement of unliganded GR in cellular processes is less clear. Our previous studies implicated unliganded GR as a positive regulator of the BRCA1 tumour suppressor gene in the absence of glucocorticoid hormone, which suggested it could play a similar role in the regulation of other genes.', 'An shRNA vector directed against GR was used to create mouse mammary cell lines with depleted endogenous levels of this receptor in order to further characterize the role of GR in breast cells. An expression microarray screen for targets of unliganded GR was performed using our GR-depleted cell lines maintained in the absence of glucocorticoids. Candidate genes positively regulated by unliganded GR were identified, classified by Gene Ontology and Ingenuity Pathway Analysis, and validated using quantitative real-time reverse transcriptase PCR. Chromatin immunoprecipitation and dual luciferase expression assays were conducted to further investigate the mechanism through which unliganded GR regulates these genes.', 'Expression microarray analysis revealed 260 targets negatively regulated and 343 targets positively regulated by unliganded GR. A number of the positively regulated targets were involved in pro-apoptotic networks, possibly opposing the activity of liganded GR targets. Validation and further analysis of five candidates from the microarray indicated that two of these, Hsd11b1 and Ch25h, were regulated by unliganded GR in a manner similar to Brca1 during glucocorticoid treatment. Furthermore, GR was shown to interact directly with and upregulate the Ch25h promoter in the absence, but not the presence, of hydrocortisone (HC), confirming our previously described model of gene regulation by unliganded GR.",
            "output": [
                "Does expression microarray identify the unliganded glucocorticoid receptor as a regulator of gene expression in mammary epithelial cells?"
            ]
        },
        {
            "id": "task847-c72173f48aff457483c60ffeb77720e7",
            "input": "Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors.', 'We evaluated the extent of promoter methylation of\\xa0genes previously reported as aberrantly methylated in prostate cancer (AIM1,\\xa0APC, CCND2, GPX3, GSTP1, MCAM, RAR\u03b22, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p \u22640.05 considered statistically significant.', 'The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p\\xa0= 0.05).",
            "output": [
                "Is gSTP1 promoter methylation associated with recurrence in early stage prostate cancer?"
            ]
        },
        {
            "id": "task847-95ddae6bd3f145b09f7a7a15b0778b75",
            "input": "Normal voiding in neurologically intact patients is triggered by the release of tonic inhibition from suprapontine centers, allowing the pontine micturition center to trigger the voiding reflex. Supraspinal mechanisms of voluntary voiding in humans are just beginning to be described via functional neuroimaging. We further elucidated brain activity processes during voiding using functional magnetic resonance imaging in normal females to gain better understanding of normal voiding as well as changes that may occur in voiding dysfunction.', 'We screened 13 healthy premenopausal female volunteers using baseline clinic urodynamics to document normal voiding parameters. We then recorded brain activity via functional magnetic resonance imaging and simultaneous urodynamics, including the pressure flow voiding phase. After motion correction of functional magnetic resonance images we performed activation and connectivity analyses in 10 subjects.', 'Group analysis revealed consistent activation areas, including regions for motor control (cerebellum, thalamus, caudate, lentiform nucleus, red nucleus, supplementary motor area and post-central gyrus), emotion (anterior/posterior cingulate gyrus and insula), executive function (left superior frontal gyrus) and a focal region in the pons. Connectivity analysis demonstrated strong interconnectivity of the pontine micturition center with many short-range and long-range cortical clusters.",
            "output": [
                "Does functional magnetic resonance imaging during urodynamic testing identify brain structures initiating micturition?"
            ]
        },
        {
            "id": "task847-0b947d36562a440195c986c488f99635",
            "input": "22q11 deletion syndrome arises from recombination between low-copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deletions distal to the typically deleted region result in a similar cardiac phenotype but lack in extracardiac features of the syndrome, suggesting that a second haploinsufficient gene maps to this interval.', 'The transcription factor HIC2 is lost in most distal deletions, as well as in a minority of typical deletions. We used mouse models to test the hypothesis that HIC2 hemizygosity causes congenital heart disease.', 'We created a genetrap mouse allele of Hic2. The genetrap reporter was expressed in the heart throughout the key stages of cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal before embryonic day E10.5, whereas the heterozygous condition exhibited a partially penetrant late lethality. One third of heterozygous embryos had a cardiac phenotype. MRI demonstrated a ventricular septal defect with over-riding aorta. Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages. Microarray analysis revealed increased expression of Bmp10.",
            "output": [
                "Is hIC2 a novel dosage-dependent regulator of cardiac development located within the distal 22q11 deletion syndrome region?"
            ]
        },
        {
            "id": "task847-ec8d2607c8d94a95a1574206de9ba7b9",
            "input": "Accumulating evidence suggests that the balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for controlling atherosclerotic disease. We hypothesized that a combination therapy with anti-CD3 antibody (CD3-Ab) and IL-2/anti-IL-2 monoclonal antibody complex (IL-2 complex) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice.', 'We treated apolipoprotein E-deficient mice fed a high-cholesterol diet with vehicle, CD3-Ab, IL-2 complex, or their combination. Mice receiving the combination therapy had markedly reduced atherosclerotic lesions than mice treated with CD3-Ab or IL-2 complex alone. In addition, a striking increase in the Treg/Teff ratio of lymphoid organs and atherosclerotic lesions, along with plaque stabilization characterized by decreased macrophage content and increased collagen content was observed. The combination treatment also markedly reduced splenic Ly6C(high) inflammatory monocytes and might induce a favorable macrophage phenotype change in atherosclerotic lesions.",
            "output": [
                "Does cD3 antibody and IL-2 complex combination therapy inhibit atherosclerosis by augmenting a regulatory immune response?"
            ]
        },
        {
            "id": "task847-d3a90c31ca69446292966b1f84279ef7",
            "input": "The pathogenesis of aortic dilatation in patients with congenital aortic valve anomalies is poorly understood. Recent studies suggest that alterations of gene expression may be related to ascending aortic aneurysm formation in these patients. Knockout of endothelial nitric oxide synthase (eNOS) and GATA5 is associated with bicuspid aortic valves in mice. To study the role of eNOS and GATA5 in human congenital aortic valve disease and aortic dilatation, we investigated their gene expression in aortic tissue from patients with unicuspid, bicuspid, and tricuspid aortic valves.', 'Samples from 84 patients (33 tricuspid, 32\\xa0bicuspid, and 19 unicuspid) were harvested intraoperatively from the ascending aorta. GATA5 and eNOS expression was determined by real-time polymerase chain reaction.', 'GATA5 and eNOS expression in the aortic wall from patients with unicuspid aortic valves (GATA5: mean [M], 2.14; standard deviation [SD], 1.72; eNOS: M, 3.40; SD, 3.83) was significantly higher than in tricuspid aortic valves (GATA5: M, 1.12; SD, 0.80; eNOS: M, 1.00; SD, 0.74; each p < 0.05). Patients with bicuspid aortic valves (GATA5: M, 1.29, SD, 1.33; eNOS: M, 1.66; SD, 1.31) had a significantly higher eNOS expression than patients with tricuspid aortic valves (p < 0.05). The expression levels of eNOS and GATA5 correlated positively with each other and negatively with the ascending aortic diameter.",
            "output": [
                "Is gATA5 and endothelial nitric oxide synthase expression in the ascending aorta related to aortic size and valve morphology?"
            ]
        },
        {
            "id": "task847-66f52948c2b54229875acf1675039211",
            "input": "CR4056 is a novel imidazoline-2 (I2 ) ligand exhibiting potent analgesic activity in animal models of pain. In this study, we investigated the effects of CR4056 in a well-established model of postoperative pain where rats develop hyperalgesia in the injured hind paw.', 'By measuring paw withdrawal threshold to mechanical pressure, we studied the pharmacology of CR4056, potential sex differences in pain perception and response to treatment, and the pharmacodynamic interaction of CR4056 with morphine.', 'Oral CR4056 and subcutaneous morphine dose-dependently reversed the hyperalgesic response. Analgesic effects of CR4056 were completely suppressed by the non-selective imidazoline I2 /\u03b12 -adrenoceptor antagonist idazoxan, were partially reduced (~30%; P < 0.05) by the selective \u03b12 -adrenoceptor antagonist yohimbine, but were not influenced by the non-selective I1 /\u03b12 -adrenoceptor antagonist efaroxan or by the \u03bc opioid receptor antagonist naloxone. We found no differences in responses to CR4056 or morphine between male and female rats. However, females had a lower pain threshold than males, and needed lower doses of drugs to reach a significant analgesia. When CR4056 and morphine were combined, their median effective doses were lower than expected for additive effects, both in males and in females. Isobolographic analysis confirmed a synergism between CR4056 and morphine.",
            "output": [
                "Does modulation of imidazoline I2 binding sites by CR4056 relieve postoperative hyperalgesia in male and female rats?"
            ]
        },
        {
            "id": "task847-e31cfcea90474234b215f099f4510d19",
            "input": "Right ventricular rupture, resulting in serious bleeding, is a life-threatening complication associated with negative-pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier between the heart and the sharp sternal edges has been successfully tested on pigs. In the present article, we demonstrate increased safety in NPWT through the use of the HeartShield device.', 'Six patients were treated with a specially designed device in combination with NPWT. The device consists of a horizontally placed disk covered in foam. The back of the T-shaped device sticks up between the sternal edges and up above skin level. This part of the device is also covered in foam. Drainage is performed through two holes at the top of the device. The device and foam are changed every second to third day, and -120 mm Hg of continuous therapy is used. Six patients were treated with traditional NPWT, serving as control group.', 'No signs of calluslike formation were seen on the right ventricle in the group treated with the HeartShield device. In the conventional NPWT control group, all six patients had calluslike formation (>1 \u00d7 2 cm2) on the anterior part of the right ventricle. All patients in the HeartShield group had grade 1 epicardial petechial bleeding (<0.5 cm2) on the right ventricle. In the control group, one patient had grade 1 (<0.5 cm2), three patients had grade 2 (0.5-2.0 cm2), and two patients had grade 3 (>2.0 cm2) epicardial petechial bleeding on the right ventricle. No major bleeding or mortality was observed in either group during the course of the study.",
            "output": [
                "Does the HeartShield device reduce the risk for right ventricular damage in patients with deep sternal wound infection?"
            ]
        },
        {
            "id": "task847-f926fbed27724ca899feb0531f8c0326",
            "input": "A distinct velocity pattern represented by a \"notch\" is observed during the time interval between the end of the systolic and the onset of the early diastolic velocity wave on longitudinal myocardial velocity curve. The origin of the post-systolic velocity notch (PSN) has not been resolved.', 'The high frame rate color tissue Doppler imaging of the apical longitudinal axis was performed in 32 healthy subjects.', 'The time delays of the PSN onset at the posterior aortic wall (AW), the mid anteroseptal wall (MAS) and the posterior mitral annulus (MA) relatively to the anterior aortic annulus (AA) were found to be significantly longer than zero (5.1 \u00b1 2.2, 6.0 \u00b1 2.3, 6.8 \u00b1 2.8 ms; p < 0.001). The amplitude was the highest at the AA when compared to the AW, the MAS and the MA (4.77 \u00b1 1.28 vs. 2.88 \u00b1 1.11, 2.15 \u00b1 0.73, 2.44 \u00b1 1.17 cm/s; p < 0.001). A second PSN spike was identifiable in 10/32 (31%) of the studied subjects at the AA. Of these, 9 (28%) exhibited a second PSN spike at the AW, 3 (9%) at the MAS and no one at the MA.",
            "output": [
                "Does the tissue Doppler imaging derived post-systolic velocity notch originate at the aortic annulus?"
            ]
        },
        {
            "id": "task847-3780c31e7d85458f9b983f62f7b84731",
            "input": "In vitamin K antagonist (VKA)-treated patients with severe hemorrhage, guidelines recommend prompt VKA reversal with prothrombin complex concentrate (PCC) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on seven-day mortality.', 'Data from consecutive patients treated with PCC were prospectively collected in 44 emergency departments. Type of hemorrhage, coagulation parameters, type of treatment and seven-day mortality mortality were recorded. Guideline-concordant administration of PCC and vitamin K (GC-PCC-K) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of eight hours after admission. Multivariate analysis was used to assess the effect of appropriate reversal on seven-day mortality in all patients and in those with intracranial hemorrhage (ICH).', 'Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months. Bleeding was gastrointestinal (32%), intracranial (32%), muscular (13%), and \"other\" (23%). In the whole cohort, seven-day mortality was 13% and 33% in patients with ICH. GC-PCC-K was performed in 38% of all patients and 44% of ICH patients. Multivariate analysis showed a two-fold decrease in seven-day mortality in patients with GC-PCC-K (odds ratio (OR)\\u2009=\\u20092.15 (1.20 to 3.88); P\\u2009=\\u20090.011); this mortality reduction was also observed when only ICH was considered (OR\\u2009=\\u20093.23 (1.53 to 6.79); P\\u2009=\\u20090.002).",
            "output": [
                "Is guideline-concordant administration of prothrombin complex concentrate and vitamin K associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment ( EPAHK study )?"
            ]
        },
        {
            "id": "task847-2501bc721e09411aa1f7e5166ea1a2a6",
            "input": "Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocysteine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice.', 'Forty-eight 7-week-old LDLr(-/-) mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed.', 'At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe.",
            "output": [
                "Does hyperhomocysteinemia independently cause and promotes atherosclerosis in LDL receptor-deficient mice?"
            ]
        },
        {
            "id": "task847-d2bbb00f8497431e9eded78a661eecb5",
            "input": "Ribavirin (RBV) remains part of several interferon-free treatment strategies even though its mechanisms of action are still not fully understood. One hypothesis is that RBV increases responsiveness to type I interferons. Pegylated Interferon alpha (PEG-IFNa) has recently been shown to alter natural killer (NK) cell function possibly contributing to control of hepatitis C virus (HCV) infection. However, the effects of ribavirin alone or in combination with IFNa on NK cells are unknown.', 'Extensive ex vivo phenotyping and functional analysis of NK cells from hepatitis C patients was performed during antiviral therapy. Patients were treated for 6 weeks with RBV monotherapy (n\\u200a=\\u200a11), placebo (n\\u200a=\\u200a13) or PEG-IFNa-2a alone (n\\u200a=\\u200a6) followed by PEG-IFNa/RBV combination therapy. The effects of RBV and PEG-IFNa-2a on NK cells were also studied in vitro after co-culture with K562 or Huh7.5 cells.', 'Ribavirin monotherapy had no obvious effects on NK cell phenotype or function, neither ex vivo in patients nor in vitro. In contrast, PEG-IFNa-2a therapy was associated with an increase of CD56bright cells and distinct changes in expression profiles leading to an activated NK cell phenotype, increased functionality and decline of terminally differentiated NK cells. Ribavirin combination therapy reduced some of the IFN effects. An activated NK cell phenotype during therapy was inversely correlated with HCV viral load.",
            "output": [
                "Does pEG-IFN alpha but not ribavirin alter NK cell phenotype and function in patients with chronic hepatitis C?"
            ]
        },
        {
            "id": "task847-955eddaef69744bbb00e10704f16786a",
            "input": "Artemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)-infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited.', 'We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor-based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes.', 'There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated.",
            "output": [
                "Are artemisinin-based combination therapies efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children?"
            ]
        },
        {
            "id": "task847-85f8f383b4c441069ee9fa38424beb4c",
            "input": "Hematuria is considered a marker of active renal disease in ANCA-associated glomerulonephritis (ANCA-GN) with induction immunosuppression often continued until hematuria has resolved. We aim to determine whether longer hematuria duration is associated with lower estimated glomerular filtration rate (eGFR) at 1 year.', 'We conducted a retrospective study of 55 patients with biopsy-proven ANCA-GN. Linear regression models were constructed to determine predictors of eGFR at 1 year. The primary exposure was hematuria (>5 rbc/hpf) duration, defined as <90 days vs. \u2265 90 days following renal biopsy. Covariates included age, gender, ANCA type, baseline eGFR, and baseline proteinuria.', 'Mean age at diagnosis was 58 years (53% male, 80% Caucasian, 38% PR3-ANCA, and 45% MPO-ANCA). At baseline, all patients had hematuria, 95% had proteinuria, and mean serum creatinine was 3.1 [standard deviation (SD) = 2.3]mg/dL. Overall, 93% were treated with steroids in combination with either cyclophosphamide or rituximab. Mean hematuria duration was 92 (SD = 77) days with 34 (62%) patients having hematuria resolution within 90 days. Older age and lower baseline eGFR were associated with lower eGFR at 1 year (p = 0.03 and p < 0.001, respectively). Hematuria resolution (<90 days vs. \u2265 90 days) was not predictive of eGFR at 1 year (p = 0.93).",
            "output": [
                "Does hematuria duration predict kidney function at 1 year in ANCA-associated glomerulonephritis?"
            ]
        },
        {
            "id": "task847-e90e37ae914d4382bff2542d1217de1c",
            "input": "Grb2 (Growth factor receptor-bound protein 2) is a key adaptor protein in maintaining the ERK activity via linking Sos1 (Son of sevenless homolog 1) or other proteins to activated RTKs, such as EGFR. Currently, little knowledge is available concerning the post-translational modification (PTM) of Grb2 except for its phosphorylation. Since emerging evidences have highlighted the importance of SUMOylation (Small ubiquitin-related modifier), a reversible PTM, in modulating protein functions, we wondered if Grb2 could be SUMOylated and thereby influences its functions especially involved in the Ras/MEK/ERK pathway.', 'SUMOylation of Grb2 was analyzed with the in vivo SUMOylation assay using the Ni2+-NTA affinity pulldown and the in vitro E.coli-based SUMOylation assay. To test the ERK activity and cell transformation, the murine fibroblast cell line NIH/3T3 and the murine colon cancer cell line CMT-93 were used for the experiments including Grb2 knockdown, ectopic re-expression, cell transformation and migration. Immunoprecipitation (IP) was employed for seeking proteins that interact with SUMO modified Grb2. Xenograft tumor model in mice was conducted to verify that Grb2 SUMOylation regulated tumorigenesis in vivo.', 'Grb2 can be SUMOylated by SUMO1 at lysine 56 (K56), which is located in the linker region between the N-terminal SH3 domain and the SH2 domain. Knockdown of Grb2 reduced the ERK activity and suppressed cell motility and tumorigenesis in vitro and in vivo, which were all rescued by stable ectopic re-expression of wild-type Grb2 but not the mutant Grb2K56R. Furthermore, Grb2 SUMOylation at K56 increased the formation of Grb2-Sos1 complex, which sequentially leads to the activation of Ras/MEK/MAPK pathway.",
            "output": [
                "Does sUMOylation of Grb2 enhance the ERK activity by increasing its binding with Sos1?"
            ]
        },
        {
            "id": "task847-38592c1e131a485ea500619478fd911c",
            "input": "This study aimed to investigate the interaction between gender and other socio-economic characteristics on sleep quality of the patients with Coronary Artery Disease (CAD).', 'This cross sectional study was conducted on 717 patients with CAD. The socio- economic status (education level, income, marital status, and place of residence) was considered as the independent variable. Besides, the study outcome was the quality of sleep which was measured using Pittsburgh Sleep Quality Index (PSQI). Gender was considered as a possible effect modifier. Two-way ANOVA was used to evaluate the interaction between gender and socio-economic factors on sleep quality. As defined by Baron and Kenny, moderator was defined as a variable that affected the direction or magnitude of the association of interest.', 'Female gender, low education level, and low income were predictive of poor sleep quality. Among female (10.0 \u00b1 4.3 vs. 7.6 \u00b1 5.0, P < 0.05), but not male patients (6.7 \u00b1 4.2 vs. 7.0 \u00b1 4.2, P > 0.05), low education was associated with poor sleep quality. Also, among female (10.0 \u00b1 4.3 vs. 5.7 \u00b1 2.5, P < 0.05), but not male patients (7.0 \u00b1 4.2 vs. 6.0 \u00b1 3.8, P > 0.05), low income was predictive of poor sleep quality. Gender did not modify the effect of other socio-economic factors on sleep quality.",
            "output": [
                "Does gender modify the effects of education and income on sleep quality of the patients with coronary artery disease?"
            ]
        },
        {
            "id": "task847-cd56c0c699ee4833bde6eede3a9915e6",
            "input": "Cross-talk between organ-specific extracellular matrix (ECM) and stem cells is often assumed but has not been directly demonstrated. We developed a protocol for the preparation of human cardiac ECM (cECM) and studied whether cECM has effects on pluripotent stem cell differentiation that may be useful for future cardiac regeneration strategies in patients with end-stage heart failure.', 'Of note, 0.3 mm-thick cECM slices were prepared from samples of myocardium from patients with end-stage non-ischaemic dilated cardiomyopathy, using a three-step protocol involving hypotonic lysis buffer, sodium dodecyl sulphate (SDS) and foetal bovine serum (FBS). Murine embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stromal cells (MSCs) were seeded and grown in standard culture, on cECM or on non-specific ECM preparations (Matrigel\u00ae or Geltrex\u00ae). Cell attachment, apoptosis induction (Caspase 3/7 activity) and metabolic activity (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium conversion) were followed. Transcriptional activation of genes involved in pluripotency; early and late myocardial development; and endothelial, ectodermal or endodermal commitment were monitored by quantitative real-time polymerase chain reaction (rtPCR). Protein expression of selected markers was confirmed by immunohistology.', 'cECM supported the proliferation of ESCs and iPSCs, and Caspase 3/7 activity was significantly lower compared with standard culture. Cardiac lineage commitment was favoured when ESCs or iPSCs were grown on cECM, as evidenced by the significantly increased mRNA expression of cardiac alpha myosin heavy polypeptide 6 (Myh6), cardiac troponin T2 (Tnnt2) and NK2 homeobox 5 (Nkx2.5) as well as positive immunohistology for cardiac troponin T and heavy-chain cardiac myosin protein. In contrast, Matrigel or Geltrex did not induce cardiac-specific markers. MSCs showed no evidence of cardiomyocyte differentiation.",
            "output": [
                "Does human cardiac extracellular matrix support myocardial lineage commitment of pluripotent stem cells?"
            ]
        },
        {
            "id": "task847-dae4017f19c2411995ccaeb101ba4aff",
            "input": "The aim of this study was to investigate whether 14-3-3\u03b7, a specific isoform of a family of proteins regulating processes such as cellular signalling, activates cell-signalling pathways and induces factors known to contribute to the pathophysiology of rheumatoid arthritis (RA). We also investigated whether 14-3-3\u03b7 is associated with more severe disease in both early and established RA.', 'We investigated the effect of 14-3-3\u03b7 on the activation of RA-relevant signalling cascades and induction of proinflammatory mediators that contribute to the joint damage process. 14-3-3\u03b7 titres from 33 patients with early RA (mean RA duration\\u2009=\\u20091.8 months) and from 40 patients with established RA were measured in serum drawn at the 3-year time point of the Behandel Strategie\u00ebn study. The relationship between 14-3-3\u03b7 titres and standard clinical variables was investigated by correlation analysis. The association with radiographic damage and radiographic progression over at least a 2-year period was investigated using univariate and multivariate regression analyses.', '14-3-3\u03b7 activated selected members of the mitogen-activated protein kinase (MAPK) family, mainly extracellular regulated kinase 1/2 and c-Jun kinase, but not p38MAPK. Activation by 14-3-3\u03b7, using levels spanning the concentration range found in RA patient serum, resulted in the induction of inflammatory transcripts such as interleukin 1 (IL-1) and IL-6 and factors linked to the joint damage process, such as receptor activator of nuclear factor \u03baB ligand and matrix metalloproteinase 1. Serum 14-3-3\u03b7 correlated significantly with rheumatoid factor (RF) (r\\u2009=\\u20090.43) and anticitrullinated protein antibodies (ACPAs) (r\\u2009=\\u20090.31) in the early RA cohort, but not with C-reactive protein (CRP) or the Disease Activity Score in 28 joints in either cohort. Serum 14-3-3\u03b7 concentrations were significantly higher in patients with radiographically assessed joint damage and in those who had radiographic progression. By multivariate analysis, we show that 14-3-3\u03b7 complemented markers such as CRP, RF and ACPA in informing RA radiographic status and/or progression.",
            "output": [
                "Is 14-3-3\u03b7 a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage?"
            ]
        },
        {
            "id": "task847-0f61a620ae0247f28eea5a17e38fd561",
            "input": "Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). Patients with early postoperative shrinkage may experience fewer subsequent complications, and consequently require less intensive surveillance.', 'Patients undergoing EVAR from 2000 to 2011 at three vascular centres (in 2 countries), who had two imaging examinations (postoperative and after 6-18 months), were included. Maximum diameter, complications and secondary interventions during follow-up were registered. Patients were categorized according to early sac dynamics. The primary endpoint was freedom from late complications. Secondary endpoints were freedom from secondary intervention, postimplant rupture and direct (type I/III) endoleaks.', 'Some 597 EVARs (71.1 per cent of all EVARs) were included. No shrinkage was observed in 284 patients (47.6 per cent), moderate shrinkage (5-9 mm) in 142 (23.8 per cent) and major shrinkage (at least 10 mm) in 171 patients (28.6 per cent). Four years after the index imaging, the rate of freedom from complications was 84.3 (95 per cent confidence interval 78.7 to 89.8), 88.1 (80.6 to 95.5) and 94.4 (90.1 to 98.7) per cent respectively. No shrinkage was an independent risk factor for late complications compared with major shrinkage (hazard ratio (HR) 3.11; P < 0.001). Moderate compared with major shrinkage (HR 2.10; P = 0.022), early postoperative complications (HR 3.34; P < 0.001) and increasing abdominal aortic aneurysm baseline diameter (HR 1.02; P = 0.001) were also risk factors for late complications. Freedom from secondary interventions and direct endoleaks was greater for patients with major sac shrinkage.",
            "output": [
                "Does early sac shrinkage predict a low risk of late complications after endovascular aortic aneurysm repair?"
            ]
        },
        {
            "id": "task847-c0d50ea6c39b4921bd263172f5e43164",
            "input": "Stigma has been suggested as a possible contributor to the high rates of treatment attrition in substance-dependent individuals, but no published empirical studies have examined this association.', 'The present paper assessed the relationship between baseline stigma variables and length of treatment stay in a sample of patients in a residential addictions treatment unit.', 'The relationship between baseline stigma variables (self-stigma, enacted stigma, and shame) and length of stay for participants (n=103) in a residential addictions treatment unit was examined.', 'Higher self-stigma predicted longer stay in residential addictions treatment, even after controlling for age, marital status, race, overall mental health, social support, enacted stigma, and internalized shame. However, other stigma variables (i.e. internalized shame, stigma-related rejection) did not reliably predict length of treatment stay.",
            "output": [
                "Does stigma predict residential treatment length for substance use disorder?"
            ]
        },
        {
            "id": "task847-25f44deeb9ca4285ade48a257f5488ec",
            "input": "Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy.', 'Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy.', 'The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 \u00b1 27.3 vs. 84.9 \u00b1 28.7, P < 0.001, receiver operating characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 \u00b1 6.9 vs. 18.4 \u00b1 6.2 mm/mm\u00b2, P = 0.004, receiver operating characteristic area under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve fibre length variable demonstrated a significant difference between the control subjects and individuals with diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 \u00b1 27.1 vs. 84.9 \u00b1 28.7, P = 0.028; corneal nerve fibre length: 20.1 \u00b1 6.3 vs. 18.4 \u00b1 6.2 mm/mm\u00b2, P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity.",
            "output": [
                "Does standardizing corneal nerve fibre length for nerve tortuosity increase its association with measures of diabetic neuropathy?"
            ]
        },
        {
            "id": "task847-d7dafcbc65544e81915aaa1b9fe5b260",
            "input": "There is a strong association between migraine and depression. The aim of this study is to identify migraine-specific factors involved in this association.', 'We conducted a cross-sectional study in a large, well-defined cohort of migraine patients (n=2533). We assessed lifetime depression using validated questionnaires, and diagnosed migraine based on the International Classification of Headache Disorders III-beta criteria. Multivariate regression analyses were conducted.', 'Of the 2533 migraineurs that were eligible, 1137 (45%) suffered from lifetime depression. The following independent factors were associated with an increased depression prevalence: i) migraine-specific risk factors: high migraine attack frequency and the presence of allodynia, ii) general factors: being a bad sleeper, female gender, high BMI, being single, smoking, and a low alcohol consumption.",
            "output": [
                "Is allodynia associated with a higher prevalence of depression in migraine patients?"
            ]
        },
        {
            "id": "task847-ed79d47a73594ca9ab1e252dad449691",
            "input": "Neoadjuvant chemotherapy (NACT) improves the prognosis of patients with esophageal cancer who respond, but it is not effective in nonresponders. Therefore, it is crucial to establish a reliable method of predicting response before initiation of chemotherapy. Hypercoagulability, which is thought to be because of upregulation of tissue factor (TF) in cancer cells, was reported to be associated with chemoresistance. The aim of this study was to investigate the association between TF expression and response to NACT in esophageal cancer.', 'In 67 patients with advanced esophageal cancer, TF expression in pretreatment biopsy samples was evaluated immunohistochemically and correlated with clinicopathologic factors and response to chemotherapy.', 'TF was expressed by 43.3% of the tumors, but there were no correlations observed with any clinicopathologic parameters examined. Clinical and histologic responses to chemotherapy were significantly worse in TF-positive patients compared with TF-negative patients. Multivariate analysis revealed that TF expression was significantly associated with a poor clinical response (P\\xa0=\\xa00.0431). TF expression was also independently associated with poor progression-free survival (P\\xa0=\\xa00.0353).",
            "output": [
                "Does tissue factor predict response to chemotherapy in esophageal cancer?"
            ]
        },
        {
            "id": "task847-da5e7ab4dead45dfae05d0a671819f69",
            "input": "The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study showed that 40 mg Olmesartan medoxomil (OM) versus placebo delayed microalbuminuria onset in patients with type 2 diabetes and normoalbuminuria.', 'One thousand seven hundred and fifty-eight ROADMAP patients (placebo arm: 877; OM arm: 881) participated in the observational follow up (OFU) with an average of 3.3 years. They received standard medical care and micro- and macrovascular events were documented. During observational follow-up 62.9% and 60.1% in the former OM and placebo group, respectively, received treatment with a RAS blocking agent. During the OFU period the systolic blood pressure (SBP) increased to mean values of 135 mm Hg in both groups. Patients who had developed microalbuminuria during ROADMAP had a higher incidence of cardio- and cerebrovascular events (OR 1.77, CI 1.03 to 3.03, P=0.039) during the OFU period compared with patients in whom this was not the case. Diabetic retinopathy was significantly reduced in the former OM group (8 [0.9%] versus 23 [2.6%], OR: 0.34, CI 0.15 to 0.78, P=0.011) and the rate of microalbuminuria was numerically reduced. Congestive heart failure requiring hospitalization (3 [0.3%] versus 12 [1.4%], OR: 0.23, CI 0.06 to 0.85, P=0.027) was reduced and there was a trend of reduced cardio-/cerebrovascular events (OM versus Pb: 73 [8.3%] versus 86 [9.8%] patients). Seven (0.8%) deaths (including 2 CV events) were reported in former placebo patients versus 3 (0.3%) (non-CV events) in former OM patients.",
            "output": [
                "Are the Randomized Olmesartan and Diabetes Microalbuminuria Prevention ( ROADMAP ) observational follow-up study : benefits of RAS blockade with olmesartan treatment sustained after study discontinuation?"
            ]
        },
        {
            "id": "task847-1b4a1cba8c7640a7910b464c8e8288dd",
            "input": "Recent studies indicate that a1-adrenergic receptors (a1-ARs) are cardioprotective by preventing cardiac myocyte death and augmenting contractility in heart failure. Although G-protein-coupled receptors are assumed to localize to and signal at the plasma membrane, we previously demonstrated that endogenous a1-ARs localize to the nuclei in adult cardiac myocytes. However, the functional consequence of this nuclear localization remains unclear. Here, we attempted to reconcile nuclear localization of a1-ARs with their physiologic function by examining a1-AR-induced contractility in adult cardiac myocytes.', 'By measuring shortening in unloaded, cultured adult cardiac myocytes, we found that the a1A-subtype regulated contractility through phosphorylation of cardiac troponin I (cTnI) at the protein kinase C (PKC) site, threonine 144. Reconstitution of an a1A-subtype nuclear localization mutant in cardiac myocytes lacking a1-ARs failed to rescue nuclear a1A-mediated phosphorylation of cTnI and myocyte contractility. Leptomycin B, the nuclear export inhibitor, also blocked a1A-mediated phosphorylation of cTnI. These data indicate that a1-AR signaling originates in the nucleus. Consistent with these observations, we localized the a1A-subtype to the inner nuclear membrane, identified PKCa, d, and e in the nucleus, and found that a1-ARs activate PKCd in nuclei isolated from adult cardiac myocytes. Finally, we found that a PKCd nuclear localization mutant blunted a1-induced phosphorylation of cTnI.",
            "output": [
                "Is nuclear localization of a1A-adrenergic receptors required for signaling in cardiac myocytes : an \u201c inside-out \u201d a1-AR signaling pathway?"
            ]
        },
        {
            "id": "task847-2d35a33727ab48439f66e5e6fefeb1f8",
            "input": "Our previous in-vivo and in-vitro studies demonstrated that inflammation accelerated the progression of atherosclerosis via the dysregulation of the low-density lipoprotein receptor (LDLr) pathway. The current study aimed to investigate the effects and their underlying mechanisms of inflammation on lipid accumulation in the radial arteries of endstage renal disease (ESRD) patients with arteriovenostomy.', '30 ESRD patients with arteriovenostomy were included. The patients were divided into two groups based on their plasma levels of C-reactive protein: a control (n = 16) and an inflamed group (n = 14). The expression of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 of the radial arteries were increased in the inflamed group. Foam cell formation and lipid droplet accumulation were examined by hematoxylin and eosin (H & E) and Oil Red O staining. Intracellular cholesterol trafficking-related proteins were examined by immunohistochemistry and immunofluorescent staining.', 'There was significant lipid accumulation in the radial arteries of the inflamed group compared with the control. Further analysis demonstrated that this accumulation was correlated with the increased protein expression of LDLr, sterol regulatory element-binding protein-2 (SREBP-2), and SREBP cleavageactivating protein (SCAP). Confocal microscopy showed that inflammation enhanced the translocation of SCAP escorting SREBP-2 from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Interestingly, upregulated LDLr expression was positively associated with the increased protein expression of mammalian target of rapamycin (mTOR), which had enhanced coexpression with SREBP-2. This finding suggests that the activation of mTOR may be involved in LDLr pathway disruption through the upregulation of SREBP-2 expression.",
            "output": [
                "Does activation of mTOR contribute to foam cell formation in the radial arteries of patients with end-stage renal disease?"
            ]
        },
        {
            "id": "task847-9a6445dcd127406990cb275b0a7bf383",
            "input": "To evaluate nitric oxide and interleukin (IL)-6, IL-8 and IL-13 in the exhaled breath of children with allergic rhinitis (AR), before and after intranasal allergen exposure.', 'A total of 49 children with AR \u2013 comprising 20 who also had episodic asthma (AR+A) and 29 without asthma (AR) \u2013 were compared with 34 healthy controls. Nitric oxide concentrations in exhaled air (eNO) and IL-6, IL-8 and IL-13 in exhaled breath condensates (EBC) were measured in winter, outside the natural allergen exposure season, before and after an intranasal allergen challenge.', 'The mean concentrations of eNO, IL-6 and IL-13 were significantly higher in the two AR groups. The concentration of IL-8 was below the assay detection limit in all EBC samples. The intranasal allergen challenge increased IL-13/EBC levels in both AR groups, but did not influence mean concentrations of eNO, IL-6 or IL-8. No challenge-related changes in IL-13/EBC were observed in the allergen-exposed controls or placebo-exposed children.",
            "output": [
                "Are nitric oxide , IL-6 and IL-13 increased in the exhaled breath condensates of children with allergic rhinitis?"
            ]
        },
        {
            "id": "task847-f1ebc879c05c4471b3ff78622d67b569",
            "input": "The cancer stem cell model links neoplastic cells with normal stem cell biology, but little is known on how normal stem cells are transformed into cancer stem cells.', 'To investigate the processes underlying the transformation of normal stem cells we developed in vitro a cancer stem cell model from human amniotic and chorionic placenta membranes. In this model we studied the expression of specific stem cell molecules by flow cytometry, and genes, by real time RT-PCR. Microscopy immunfluorescence was employed to investigate the proliferative and differentiation patterns. Fluorescence microscopy and FACS were employed to investigate the proliferative and differentiation patterns. To evaluate the tumorigenic potential of our model we injected the cells into NOD.CB17-Prkdcscid/NCrHsd mice.', 'Normal human stem cells from amniotic and chorionic placenta membranes were converted into neural cell lineages, under specific conditions, to form secondary neurospheres with a capacity for self-renewal. After extensive in vitro culture, these cells underwent spontaneous transformations and acquired a neuroblastoma (NB)-like phenotype with an elevated proliferative potential that is comparable to established neuroblastoma cell lines. The ability of these cells to transform their phenotype was evidenced by increased clonogenic ability in vitro; by augmented expression level of certain proliferation- and transformation-related genes (e.g., CCNA2, MYCN, ENPP2, GRIA3, and KIT); by the presence of multinucleated and hyperdiploid cells. We further demonstrated that the transformed phenotype is an NB by measuring the expression of NB-specific markers, disialoganglioside GD2 and N-Myc proteins.",
            "output": [
                "Are human placenta-derived neurospheres susceptible to transformation after extensive in vitro expansion?"
            ]
        },
        {
            "id": "task847-03b0b421a6794d93a89bc3d91afbe46b",
            "input": "This study was to investigate whether the expression of a disintegrin and metalloproteinase-9 (ADAM9) is correlated with the expression of hepatoma-derived growth factor (HDGF) in surgically resected non-small cell lung cancer (NSCLC), to evaluate the significance of HDGF and ADAM9 as novel molecular staging biomarkers, prognostic biomarkers and predictive biomarkers for postoperative adjuvant chemotherapy in surgically resected stage I NSCLC, to provide essential consistence proof to the possible novel pathway of HDGF-ADAM9 pathway.', 'Sixty-three cases of resected stage I NSCLC with mediastinal N2 lymph node dissection were immunohistochemically analyzed for HDGF and ADAM9 protein expression. Multivariate analysis and survival analysis were conducted.', \"HDGF and ADAM9 were observed highly expressed in NSCLC compared with normal control lung tissues (P < 0.05). HDGF high expression cases showed significantly lower survival rate (55.6 vs. 84.7 %, P = 0.009). HDGF high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.015). ADAM9 high expression cases showed significantly lower survival rate (56.9 vs. 88.7 %, P = 0.015). ADAM9 high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.021). Pearson's correlation analysis revealed that ADAM9 expression was correlated positively and significantly with HDGF expression in 63 cases of stage I NSCLC (r = 0.547, P = 0.000).",
            "output": [
                "Are hDGF and ADAM9 novel molecular staging biomarkers , prognostic biomarkers and predictive biomarkers for adjuvant chemotherapy in surgically resected stage I non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-6a579ac2baee4deaa1be0802b59ec7d8",
            "input": "Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time.', 'Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression.', 'Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, \u03b7p (2) = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, \u03b7p (2) = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, \u03b7p (2) = 0.126) and memory (p = 0.037, \u03b7p (2) = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment.",
            "output": [
                "Do brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS?"
            ]
        },
        {
            "id": "task847-c87e70333fe34f369fdea6aed06e67aa",
            "input": "Perilipin-5 (PLIN5) is a member of the perilipin family of lipid droplet (LD)-associated proteins. PLIN5 is expressed in oxidative tissues including the liver, and is critical during LD biogenesis. Studies showed that statins reduce hepatic triglyceride contents in some patients with non-alcoholic fatty liver disease and in rodent models of diet-induced hepatosteatosis. Whether statins alter triglyceride synthesis, storage, and/or utilization within the hepatocyte is unknown, though. Here we tested the hypothesis that statins alter the metabolism of LD in the hepatocyte during physiological conditions, such as fasting-induced steatosis.', 'Mice were gavaged with saline or atorvastatin, and the expression of LD-associated genes was determined in fed and fasted animals. The accumulation of triglycerides and LD was studied in mouse or human primary hepatocytes in response to statins, and following knock-down of SREBP2 or PLIN5.', 'We show that statins decrease the levels of PLIN5, but not other LD-associated genes, in both mouse liver and mouse/human primary hepatocytes, which is paralleled by a significant reduction in both intracellular triglycerides and the number of LD. We identify an atypical negative sterol regulatory sequence in the proximal promoter of mouse/human PLIN5 that recruits the transcription factor SREBP2 and confers response to statins. Finally, we show that the statin-dependent reduction of hepatocyte triglyceride contents is mimicked by partial knock-down of PLIN5; conversely, ectopic overexpression of PLIN5 reverts the statin effect.",
            "output": [
                "Is perilipin-5 regulated by statins and controls triglyceride contents in the hepatocyte?"
            ]
        },
        {
            "id": "task847-b1b6677f2ac54a8a8f78ce5177c756d1",
            "input": "Patients with newly diagnosed HIV may be part of social networks with elevated prevalence of undiagnosed HIV infection. Social network recruitment by persons with newly diagnosed HIV may efficiently identify undiagnosed cases of HIV infection. We assessed social network recruitment as a strategy for identifying undiagnosed cases of HIV infection.', 'In a sexually transmitted infection (STI) clinic in Lilongwe, Malawi, 3 groups of 45 \"seeds\" were enrolled: STI patients with newly diagnosed HIV, STI patients who were HIV-uninfected, and community controls. Seeds were asked to recruit up to 5 social \"contacts\" (sexual or nonsexual). Mean number of contacts recruited per group was calculated. HIV prevalence ratios (PRs) and number of contacts needed to test to identify 1 new case of HIV were compared between groups using generalized estimating equations with exchangeable correlation matrices.', 'Mean number of contacts recruited was 1.3 for HIV-infected clinic seeds, 1.8 for HIV-uninfected clinic seeds, and 2.3 for community seeds. Contacts of HIV-infected clinic seeds had a higher HIV prevalence (PR: 3.2, 95% confidence interval: 1.3 to 7.8) than contacts of community seeds, but contacts of HIV-uninfected clinic seeds did not (PR: 1.1, 95% confidence interval: 0.4 to 3.3). Results were similar when restricted to nonsexual contacts. To identify 1 new case of HIV, it was necessary to test 8 contacts of HIV-infected clinic seeds, 10 contacts of HIV-uninfected clinic seeds, and 18 contacts of community seeds.",
            "output": [
                "Are sTI patients effective recruiters of undiagnosed cases of HIV : results of a social contact recruitment study in Malawi?"
            ]
        },
        {
            "id": "task847-c7225fbde5ba40618974dd8472d16ac8",
            "input": "To determine the role of repetitive endocardial focal activations and Purkinje fibers in the maintenance of long duration ventricular fibrillation (LDVF, VF>1 minute) in canine hearts in vivo.', \"The study was conducted in electrophysiological laboratory of Shanghai Ruijin hospital from July 2010 to August 2012. A 64-electrode basket was introduced through a carotid artery into the left ventricle (LV) of 11 beagle dogs for global endocardial electrical mapping. In the Lugol's solution group (n=5), the subendocardium was ablated by washing with Lugol's solution. In the control group, (n=6) saline was used for ablation. Before and after saline or Lugol ablation, we determined QRS duration and QT/QTc interval in sinus rhythm (SR). We also measured the activation rates in the first 2 seconds of each minute during 7 minutes of VF for each group. If VF terminated spontaneously in less than 7 minutes, the VF segments used in activation rate analysis were reduced accordingly.\", \"At the beginning of VF there was no difference between the groups in the activation rate. However, after 1 minute of LDVF the Lugol's solution group had significantly slower activation rate than the control group. In the control group, all episodes of LDVF (6/6) were successfully sustained for 7 minutes, while in the Lugol's solution group 4/5 episodes of LDVF spontaneously terminated before 7 minutes (4.8\u00b11.4 minutes) (P=0.015). In the control group, at 5.1\u00b11.3 minutes of LDVF, a successive, highly organized focal LV endocardial activation pattern was observed. During this period, activations partly arose in PF and spread to the working ventricular myocardium. Mapping analysis showed that these events were consistent with repetitive endocardial focal activations. No evidence of similar focal activations was observed in the Lugol's solution group.",
            "output": [
                "Does endocardial focal activation originating from Purkinje fibers play a role in the maintenance of long duration ventricular fibrillation?"
            ]
        },
        {
            "id": "task847-954d96e783c14511a6a24ad452a066e2",
            "input": "Allergic contact dermatitis (ACD) is the most common occupational disease. Although murine contact hypersensitivity provides a framework for understanding ACD, it carries important differences from its human counterpart. Unlike the contact hypersensitivity model, which is induced by potent sensitizers (ie, dinitrofluorobenzene), human ACD is induced by weak-to-moderate sensitizers (ie, nickel), which cannot induce reactions in mice. Distinct hapten-specific immune-polarizing responses to potent inducers were suggested in mice, with unclear relevance to human ACD.', 'We explored the possibility of distinct T-cell polarization responses in skin to common clinically relevant ACD allergens.', 'Gene-expression and cellular studies were performed on common allergens (ie, nickel, fragrance, and rubber) compared with petrolatum-occluded skin, using RT-PCR, gene arrays, and immunohistochemistry.', 'Despite similar clinical reactions in all allergen groups, distinct immune polarizations characterized different allergens. Although the common ACD transcriptome consisted of 149 differentially expressed genes across all allergens versus petrolatum, a much larger gene set was uniquely altered by individual allergens. Nickel demonstrated the highest immune activation, with potent inductions of innate immunity, TH1/TH17 and a TH22 component. Fragrance, and to a lesser extent rubber, demonstrated a strong TH2 bias, some TH22 polarization, and smaller TH1/TH17 contributions.",
            "output": [
                "Does molecular profiling of contact dermatitis skin identify allergen-dependent differences in immune response?"
            ]
        },
        {
            "id": "task847-6b374629f06c48b6ad349d6efc95b1c8",
            "input": "To test the effect of a high reliability organization (HRO) intervention on patient lengths of stay in the CVICU and hospital. The authors proposed that (1) higher safety related evidence based protocol (SREBP) team compliance scores and (2) lower SREBP milestone scores are associated with shorter lengths of CVICU and hospital stay.', 'A prospective, longitudinal observational evaluation was used to assess the effects of SREBP-focused rounding processes and a milestone-tracking tool.', \"United States, university academic medical center's 27-bed CVICU.\", 'Six hundred sixty-five adult cardiac surgery patients and the CVICU care team (100 registered nurses and 16 clinical providers) participated.', \"Team compliance was the proportion of SREBP-related team behaviors exhibited during daily rounds. Patients' milestone scores were the cumulative difference between actual and expected times for 4 SREBP milestones over 48 hours. Milestones achieved earlier than expected indicated reduced complication risk, and milestones achieved later than expected indicated increased risk. As team compliance increased, CVICU length of stay decreased 0.66 (95% CI: -0.04 to 1.28; p = 0.08) days; hospital stay decreased 0.89 times (95% CI: 0.77-1.03; p = 0.008). As the mean milestone scores increased from -7 to 12, length of ICU stay increased 2.63 (95% CI: 1.66-3.59; p<0.001) days; hospital length of stay increased 1.44 times (95% CI: 1.23-1.7; p = 0.05).",
            "output": [
                "Does implementing goal-directed protocols reduce length of stay after cardiac surgery?"
            ]
        },
        {
            "id": "task847-242e771c8f594cf59e720f6c802b5aa7",
            "input": "Early acute kidney injury (AKI) following trauma is associated with multiorgan failure and mortality. Leukotrienes have been implicated both in AKI and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO-activating protein (FLAP) in the first step of leukotriene production following trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph, which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI.', 'Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished via cannulation of the mesenteric duct. Extent of kidney injury was determined via histology score and verified by urinary neutrophil gelatinase-associated lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and colocalization was determined by fluorescence resonance energy transfer signal intensity. The end leukotriene products of 5-LO were determined in urine.', 'AKI was evident in the T/HS group by derangement in kidney tubule architecture and confirmed by neutrophil gelatinase-associated lipocalin assay, whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD during T/HS decreased the associations between 5-LO and FLAP demonstrated by fluorescence resonance energy transfer microscopy and decreased leukotriene production in urine.",
            "output": [
                "Does mesenteric lymph diversion abrogate 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock?"
            ]
        },
        {
            "id": "task847-72faa772e9ee4b00a8ea2bd7f2a42024",
            "input": "Historically, fever, pneumonia, and sepsis after trauma are ascribed to pain and poor pulmonary toilet. No evidence supports that assertion however, and no known biologic mechanisms link injury to infection. Our studies show that injured tissues release mitochondria (MT). Mitochondrial damage-associated molecular patterns (mtDAMPs) however can mimic bacterial pathogen-associated danger molecules and attract neutrophils (PMN). We hypothesized that mtDAMPs from traumatized tissue divert neutrophils from the lung, causing susceptibility to infection.', 'Anesthetized rats (6-10 per group) underwent pulmonary contusion (PC) by chest percussion. When modeling traumatic MT release, some rats had MT isolated from the liver (equal to 5% liver necrosis) injected intraperitoneally (IPMT). Negative controls had PC plus buffer intraperitoneally. Positive controls underwent PC plus cecal ligation and puncture. At 16 hours, bronchoalveolar and peritoneal lavages were performed. Bronchoalveolar lavage fluid (BALF) and peritoneal lavage fluid were assayed for PMN count, albumin, interleukin \u03b2, (IL-\u03b2), and CINC-1. Assays were normalized to blood urea nitrogen to calculate absolute concentrations.', 'PC caused alveolar IL-1\u03b2 and CINC production and a 34-fold increase in BALF neutrophils. As expected, IPMT increased peritoneal IL-1\u03b2 and CINC and attracted PMN to the abdomen. However, remarkably, IPMT after PC attenuated BALF cytokine accumulation and decreased BALF PMN. Cecal ligation and puncture had no direct effect on BALF PMNs but, like IPMT, blunted BALF leukocytosis after PC.",
            "output": [
                "Do mitochondrial damage-associated molecular patterns released by abdominal trauma suppress pulmonary immune responses?"
            ]
        },
        {
            "id": "task847-1736fe12eb2443d8a33a4a15ee468f00",
            "input": "In previous studies, we could show that the B vitamin nicotinamide (NAM) enhanced antimicrobial activity of neutrophils. Here, we assessed the effects of NAM in two models of experimental colitis.', 'Colitis was induced in C57BL/6 mice either by oral infection with Citrobacter rodentium or by DSS (dextran sodium sulphate) administration, and animals were systemically treated with NAM. Ex vivo bacterial clearance was assessed in murine and human whole blood, as well as isolated human neutrophils. In C. rodentium-induced colitis, NAM treatment resulted in markedly decreased systemic bacterial invasion, histological damage and increased fecal clearance of C. rodentium by up to 600-fold. In contrast, NAM had no effect when administered to neutrophil-depleted mice. Ex vivo stimulation of isolated human neutrophils, as well as murine and human whole blood with NAM led to increased clearance of C. rodentium and enhanced expression of antimicrobial peptides in neutrophils. Moreover, NAM treatment significantly ameliorated the course of DSS colitis, as assessed by body weight, histological damage and myeloperoxidase activity.",
            "output": [
                "Does nicotinamide treatment ameliorate the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance?"
            ]
        },
        {
            "id": "task847-141292037fee4b64b16a35fb02248cab",
            "input": "Insecticide resistance in Trialeurodes vaporariorum W. is unknown in the species' northern distribution range where it inhabits mainly commercial greenhouses. Resistance development in whiteflies feeding on year-round crops in greenhouses is possible owing to the use of chemical treatments to back up biocontrol. The authors tested the response levels to spiromesifen, pymetrozine and imidacloprid in whiteflies collected from seven greenhouses within a 35\\u2009km radius in western Finland.\", 'All except one (PR) population had LC50 values below the recommended concentrations for the tested compounds. However, some populations showed reduced susceptibility to pymetrozine in comparison with the reference susceptible population. Resistance ratios to pymetrozine were highly variable (resistance ratio 0.5-39.7), even among closely located greenhouses, and higher than those for imidacloprid (resistance ratio 1.05-10.5) and spiromesifen (resistance ratio 0.8-11.5). LC50 values and application frequencies of pymetrozine correlated positively among the sampled populations.",
            "output": [
                "Is variation in mortality among populations higher for pymetrozine than for imidacloprid and spiromesifen in Trialeurodes vaporariorum in greenhouses in Finland?"
            ]
        },
        {
            "id": "task847-1df1282846ed44a4bbfb0d6ec27bf7a8",
            "input": "Rheumatoid arthritis (RA) has been associated with premature immunosenescence and an increased prevalence of age-related morbidities including poor cognitive function.', 'We explored the relationships among lymphocyte subsets and memory in RA.', 'Thirty patients with RA and 19 age-matched healthy controls took part in this study. Cognitive function stress and depression scores were evaluated by structured clinical questionnaires. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate the following subsets: B cells, activated and na\u00efve/memory T cells, regulatory FoxP3+ T (Treg) cells, Th17+ cells, NK cells and senescence-associated CD28- T cells.', 'RA patients were more depressed than controls, but stress levels were similar in the 2 groups. Patients had impaired memory performance compared to controls, demonstrated by lower Mini-Mental State Examination scores and logical and working memories (all p < 0.0001). These group effects remained significant after correcting for depression and age. Patients had expansion of regulatory T cells, na\u00efve CD4+ T cells and CD8+CD28- cells but reduced percentages of B cells and memory CD8+CD45RO+ T cells compared to controls. CD8+CD28- and CD8+CD45RO+ T cells were found to be negatively associated with memory.",
            "output": [
                "Is premature immunosenescence associated with memory dysfunction in rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-59cde4223a8046b4ad4445c91a01c562",
            "input": "Gram negative infection is a major determinant of morbidity and survival. Traditional teaching suggests that burn wound infections in different centres are caused by differing sets of causative organisms. This study established whether Gram-negative burn wound isolates associated to clinical wound infection differ between burn centres.', 'Studies investigating adult hospitalised patients (2000-2010) were critically appraised and qualified to a levels of evidence hierarchy. The contribution of bacterial pathogen type, and burn centre to the variance in standardised incidence of Gram-negative burn wound infection was analysed using two-way analysis of variance.', \"Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanni, Enterobacter spp., Proteus spp. and Escherichia coli emerged as the commonest Gram-negative burn wound pathogens. Individual pathogens' incidence did not differ significantly between burn centres (F (4, 20)\\u200a=\\u200a1.1, p\\u200a=\\u200a0.3797; r2\\u200a=\\u200a9.84).",
            "output": [
                "Do gram negative wound infection in hospitalised adult burn patients -- systematic review and metanalysis-?"
            ]
        },
        {
            "id": "task847-7ccee5885adb407bbd1b1d8ed8535d8c",
            "input": "Increased potassium intake has been shown to lower blood pressure (BP) even in the presence of high sodium consumption however the role of dietary potassium on vascular function has received less attention. The aim of this study was to evaluate the relationship between habitual intake of sodium (Na) and potassium (K) and measures of arterial stiffness and wave reflection.', 'Thirty-six young healthy adults (21 M, 15 F; 24 \u00b1 0.6 yrs; systolic BP 117 \u00b1 2; diastolic BP 63 \u00b1 1 mmHg) recorded their dietary intake for 3 days and collected their urine for 24 hours on the 3rd day. Carotid-femoral pulse wave velocity (PWV) and the synthesis of a central aortic pressure waveform (by radial artery applanation tonometry and generalized transfer function) were performed. Aortic augmentation index (AI), an index of wave reflection, was calculated from the aortic pressure waveform.', 'Subjects consumed an average of 2244 kcals, 3763 mg Na, and 2876 mg of K. Average urinary K excretion was 67 \u00b1 5.3 mmol/24 hr, Na excretion was 157 \u00b1 11 mmol/24 hr and the average Na/K excretion ratio was 2.7 \u00b1 0.2. An inverse relationship between AI and K excretion was found (r =\\u2009-0.323; p < 0.05). A positive relationship between AI and the Na/K excretion ratio was seen (r = 0.318; p < 0.05) while no relationship was noted with Na excretion alone (r = 0.071; p > 0.05). Reflection magnitude, the ratio of reflected and forward waves, was significantly associated with the Na/K excretion ratio (r = 0.365; p <0.05) but not Na or K alone. PWV did not correlate with Na or the Na/K excretion ratio (p > 0.05) but showed an inverse relationship with K excretion (r =\\u2009-0.308; p < 0.05).",
            "output": [
                "Is lower potassium intake associated with increased wave reflection in young healthy adults?"
            ]
        },
        {
            "id": "task847-79371c926d8d4d62b6f20758d4b33f79",
            "input": "To understand whether the relationship between young children's autonomic nervous system (ANS) responses predicted their BMI, or vice versa, the association between standardized BMI (zBMI) at 2, 3.5, and 5 years of age and ANS reactivity at 3.5-5 years of age, and whether zBMI predicts later ANS reactivity or whether early ANS reactivity predicts later zBMI, was studied.\", \"Low-income, primarily Latino children (n=112) were part of a larger cohort study of mothers recruited during early pregnancy. Study measures included maternal prenatal weight, children's health behaviors (i.e., time watching television, fast food consumption, and time playing outdoors), children's height and weight at 2, 3.5, and 5 years, and children's ANS reactivity at 3.5 and 5 years. ANS measures of sympathetic nervous system (i.e., pre-ejection period) and parasympathetic nervous system (i.e., respiratory sinus arrhythmia) activity were monitored during rest and four challenges. Reactivity was calculated as the difference between mean challenge response and rest. Structural equation models analyzed the relationship between children's zBMI at 2, 3.5, and 5 years and ANS reactivity at 3.5 and 5 years, adjusting for mother's BMI, children's behaviors, and changes in height.\", 'There was no association between zBMI and ANS cross-sectionally. Children with high zBMI at 2 or 3.5 years or large zBMI increases from 2 to 3.5 years of age had decreased sympathetic activity at 5 years. Neither sympathetic nor parasympathetic reactivity at 3.5 years predicted later zBMI.",
            "output": [
                "Does latino children 's body mass index at 2-3.5 years predict sympathetic nervous system activity at 5 years?"
            ]
        },
        {
            "id": "task847-990d0a0f042b437f9d49a2a22a49881b",
            "input": "Post-traumatic stress disorder (PTSD) is a common psychological problem following natural disasters. Although pre-disaster risk factors are important for early detection and proactive support, the examination of such has been limited to sociodemographic factors, which were largely unaffected by the disasters. We examined the association between pre-disaster physical functioning and lifestyle and PTSD symptoms five months after the earthquake in the Great East Japan Earthquake survivors who were participating in a pre-existing cohort study.', 'We designed a retrospective cohort study of a cooperative association in Sendai from August 2010 to August 2011. In 2010, lifestyle, physical condition, and sociodemographic factors were examined by self-reported questionnaires completed by 522 employees of this organization. We also measured the leg extension power of all the participants. PTSD symptoms were evaluated by the Japanese version of the Impact of Event Scale-Revised (IES-R-J) following the earthquake of 2011.', 'In multivariate linear regression analysis, leg extension power (\u03b2\\u200a=\\u200a-0.128, P\\u200a=\\u200a0.025), daily drinking (\u03b2 \\u200a=\\u200a0.203, P\\u200a=\\u200a0.006), and depressive symptoms (\u03b2 \\u200a=\\u200a0.139, P\\u200a=\\u200a0.008) were associated with total score of the IES-R-J among men. Moreover, for the IES-R-J subscale, leg extension power was also negatively associated with Intrusion (\u03b2\\u200a=\\u200a-0.114, P\\u200a=\\u200a0.045) and Hyperarousal (\u03b2\\u200a=\\u200a-0.163, P\\u200a=\\u200a0.004) after adjusting for all other significant variables. For women, hypertension (\u03b2 \\u200a=\\u200a0.226, P\\u200a=\\u200a0.032) and depressive symptoms (\u03b2 \\u200a=\\u200a0.205, P\\u200a=\\u200a0.046) were associated with the total score of the IES-R-J.",
            "output": [
                "Is leg extension power a pre-disaster modifiable risk factor for post-traumatic stress disorder among survivors of the Great East Japan Earthquake : a retrospective cohort study?"
            ]
        },
        {
            "id": "task847-1126257643ae431797fdcba8a7ad085a",
            "input": "The hypothesis of this study is that long-term high-fat diets (HFD) induce perivascular adipose tissue (PVAT) dysfunction characterized by a redox imbalance, which might contribute to aggravate endothelial dysfunction in obesity.', 'C57BL/6J mice were fed either control or HFD (45% kcal from fat) for 32 weeks. Body weight, lumbar and mesenteric adipose tissue weights were significantly higher in HFD animals compared to controls. The anticontractile effect of PVAT in mesenteric arteries (MA) was lost after 32 week HFD and mesenteric endothelial-dependent relaxation was significantly impaired in presence of PVAT in HFD mice (Emax\\u200a=\\u200a71.0\u00b15.1 vs Emax\\u200a=\\u200a58.5\u00b14.2, p<0.001). The inhibitory effect of L-NAME on Ach-induced relaxation was less intense in the HFD group compared with controls suggesting a reduction of endothelial NO availability. Expression of eNOS and NO bioavailability were reduced in MA and almost undetectable in mesenteric PVAT of the HFD group. Superoxide levels and NOX activity were higher in PVAT of HFD mice. Apocynin only reduced contractile responses to NA in HFD animals. Expression of ec-SOD and total SOD activity were significantly reduced in PVAT of HFD mice. No changes were observed in Mn-SOD, Cu/Zn-SOD or catalase. The ratio [GSSG]/([GSH]+[GSSG]) was 2-fold higher in the mesenteric PVAT from HFD animals compared to controls.",
            "output": [
                "Does imbalance between pro and anti-oxidant mechanisms in perivascular adipose tissue aggravate long-term high-fat diet-derived endothelial dysfunction?"
            ]
        },
        {
            "id": "task847-b0fac2bf8d9649698856b124d79135e9",
            "input": "Cognitive changes after ischemic stroke are often overlooked, particularly acutely and in patients with mild or transient deficits. We assessed patients with transient ischemic attack (TIA)/minor stroke with serial cognitive screening tests. We tested the hypothesis that mild acute deficits are transient and improve after TIA/minor stroke.', 'Patients with acute TIA/minor ischemic stroke, without a history of cognitive impairment, presenting with a National Institute of Health Stroke Scale score \u22643 were assessed <72 hours of onset. Patients were administered the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) at days 1, 7, 30, and 90. Cognitive impairment was defined as MoCA <26 and MMSE \u226426.', 'One hundred patients with a median (interquartile range) National Institute of Health Stroke Scale score of 1 (2) and median age of 68 (20) years were included. Baseline median MoCA score (26 [4]) was lower than the MMSE (29 [2]; P<0.0001). Cognitive impairment was detected in 54 of 100 patients (54%) with MoCA and 16 of 100 (16%; P=0.001) with MMSE. MoCA scores improved at day 7 (27 [5]), day 30 (28 [2]), and day 90 (28 [2]; P<0.0001). Resolution of cognitive deficits was because of resolution of recall deficits.",
            "output": [
                "Do serial montreal cognitive assessments demonstrate reversible cognitive impairment in patients with acute transient ischemic attack and minor stroke?"
            ]
        },
        {
            "id": "task847-2e1ed3bae24a4e9dba4ba4536f6f727a",
            "input": "To determine the frequency of hyperintense cortical signal (HCS) on T1-weighted precontrast magnetic resonance (MR) images in progressive multifocal leukoencephalopathy (PML) patients, its association with seizure risk and immune reconstitution inflammatory syndrome (IRIS), and its pathologic correlate.', 'We reviewed clinical data including seizure history, presence of IRIS, and MR imaging scans from PML patients evaluated at our institution between 2003 and 2012. Cases that were diagnosed either using cerebrospinal fluid JC virus (JCV) polymerase chain reaction, brain biopsy, or autopsy, and who had MR images available were included in the analysis (n=49). We characterized pathologic findings in areas of the brain that displayed HCS in 2 patients and compared them with isointense cortex in the same individuals.', 'Of 49 patients, 17 (34.7%) had seizures and 30 (61.2%) had HCS adjacent to subcortical PML lesions on MR images. Of the 17 PML patients with seizures, 15 (88.2%) had HCS compared with 15 of 32 (46.9%) patients without seizures (p=0.006). HCS was associated with seizure development with a relative risk of 4.75 (95% confidence interval=1.2-18.5, p=0.006). Of the 20 patients with IRIS, 16 (80.0%) had HCS compared with 14 of 29 (49.3%) patients without IRIS (p=0.04). On histological examination, HCS areas were associated with striking JCV-associated demyelination of cortical and subcortical U fibers, significant macrophage infiltration, and a pronounced reactive gliosis in the deep cortical layers.",
            "output": [
                "Does hyperintense cortical signal on magnetic resonance imaging reflect focal leukocortical encephalitis and seizure risk in progressive multifocal leukoencephalopathy?"
            ]
        },
        {
            "id": "task847-0b964b95c9c34934abb93a64b6090a50",
            "input": "The aim of this study was to examine the efficacy and surgical success rates of amniotic membrane (AM) transplantation performed for corneal perforation closure using a novel technique.', 'This study included 6 eyes from 6 patients with corneal perforation who had received AM transplantation between May 2011 and April 2012. The AM was collected from human placenta shortly after cesarean section. In surgery, the AM was folded into pleats and used to plug the wound using 10-0 nylon suture. The wound was then covered with an AM seal. After reepithelialization and AM scarring, sutures were removed.', 'All 6 patients had successful wound closure with 1 surgery. One patient underwent optical keratoplasty later, and 1 patient required combined preserved sclera transplantation. The absolute value of astigmatism decreased to <3.50 diopters (D) 3 months after surgery and to <3.00 D 6 months after surgery in patients with peripheral AM transplants. The visual acuity gradually improved over the first 3 months after surgery, and visual acuity gains were maintained at the 6-month postoperative mark.",
            "output": [
                "Do `` Pleats fold '' technique of amniotic membrane transplantation for management of corneal perforations?"
            ]
        },
        {
            "id": "task847-bf74131c51b941a4ac97b8c496bb336c",
            "input": "Self-reported health-related quality of life (HRQL) and changes in HRQL have been shown to predict mortality and/or adverse events in patients with coronary artery disease. MacNew Heart Disease HRQL questionnaire scores were examined as predictors of 4-year all-cause mortality.', 'Following referral for angioplasty in 385 patients with coronary artery disease, data were analyzed for differences in all-cause mortality by MacNew Global and subscale baseline and 1- and 3-month change scores (deteriorated \u22650.50; unchanged (-0.49 to +0.49); and improved \u22650.50 points).', 'Mean baseline, 1-month, and 3-month MacNew Global and subscale scores were similar in survivors and non-survivors. Mean 1- and 3-month Global and emotional subscale and mean 1-month social subscale change scores decreased more in non-survivors than survivors. Compared with patients whose Global MacNew HRQL scores improved at one month, 4-year all-cause mortality hazard ratio (HR) was higher in patients whose HRQL deteriorated (HR, 1.70, 95% CI, 1.09, 2.65; p=0.021). Compared with patients whose Global MacNew HRQL improved at three months, 4-year all-cause mortality was higher in both patients whose HRQL had deteriorated (HR, 2.07, 95% CI, 1.29, 3.32; p=0.003) and patients with unchanged HRQL (HR, 2.62, 95% CI, 1.11, 6.17; p=0.028).",
            "output": [
                "Does change in health-related quality of life in patients with coronary artery disease predict 4-year mortality?"
            ]
        },
        {
            "id": "task847-f7e8deac360f4f949099e9bf21ed6c09",
            "input": "Certain aspects of total knee arthroplasty (TKA) in severely and morbidly obese (SMO) patients (BMI \u2265 35 kg/m(2)) remain controversial. This study aimed to assess the duration of TKA surgery and hospital stay in relation to patients' BMI.\", 'Three operative times during TKA surgery were recorded: tourniquet time, to determine surgical difficulty, total surgical time, to assess the difficulty of achieving anaesthesia, and time in the surgical area, to assess patient management in the surgical area. Length of hospital stay was also calculated. Data were collected prospectively from consecutive patients and were recorded in a database for retrospective analysis.', 'Data were obtained from 922 consecutive patients undergoing TKA. The non-obese group comprised 418 patients (45.3%), obese group Class I 331 (36%), and the SMO group (Class II-III) 173 (18.7%). Mean tourniquet time was 53 min, mean total surgical time was 84 min, and mean time in the surgical area was 132 min. There were no differences according to BMI group. Median length hospital stay (LHS) was 6 days in all patients regardless of BMI. Factors that significantly prolonged LHS were ASA III-IV and pre-operative haemoglobin between 12 and 13 g/dl.",
            "output": [
                "Does severe and morbid obesity ( BMI \u2265 35 kg/m ( 2 ) ) increase surgical time and length of hospital stay in total knee arthroplasty surgery?"
            ]
        },
        {
            "id": "task847-2941c7d2ede048f381019b2f8638c0f8",
            "input": "While inflammation predicts mortality in treated human immunodeficiency virus (HIV) infection, the prognostic significance of gut barrier dysfunction and phenotypic T-cell markers remains unclear.', 'We assessed immunologic predictors of mortality in a case-control study within the Longitudinal Study of the Ocular Complications of AIDS (LSOCA), using conditional logistic regression. Sixty-four case patients who died within 12 months of treatment-mediated viral suppression were each matched to 2 control individuals (total number of controls, 128) by duration of antiretroviral therapy-mediated viral suppression, nadir CD4(+) T-cell count, age, sex, and prior cytomegalovirus (CMV) retinitis. A similar secondary analysis was conducted in the SCOPE cohort, which had participants with less advanced immunodeficiency.', 'Plasma gut epithelial barrier integrity markers (intestinal fatty acid binding protein and zonulin-1 levels), soluble CD14 level, kynurenine/tryptophan ratio, soluble tumor necrosis factor receptor 1 level, high-sensitivity C-reactive protein level, and D-dimer level all strongly predicted mortality, even after adjustment for proximal CD4(+) T-cell count (all P \u2264 .001). A higher percentage of CD38(+)HLA-DR(+) cells in the CD8(+) T-cell population was a predictor of mortality before (P = .031) but not after (P = .10) adjustment for proximal CD4(+) T-cell count. Frequencies of senescent (defined as CD28(-)CD57(+) cells), exhausted (defined as PD1(+) cells), naive, and CMV-specific T cells did not predict mortality.",
            "output": [
                "Do gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection?"
            ]
        },
        {
            "id": "task847-0a022a931f5244bcaabbeea3c0437b29",
            "input": "Vitamin D, an important modulator of the immune system, has been shown to protect mucosal barrier homeostasis. This study investigates the effects of vitamin D deficiency on infection-induced changes in intestinal epithelial barrier function in vitro and on Citrobacter rodentium-induced colitis in mice.', 'Polarized epithelial Caco2-bbe cells were grown in medium with or without vitamin D and challenged with enterohemorrhagic Escherichia coli O157:H7. Barrier function and tight junction protein expression were assessed. Weaned C57BL/6 mice were fed either a vitamin D-sufficient or vitamin D-deficient diet and then infected with C. rodentium. Disease severity was assessed by histological analysis, intestinal permeability assay, measurement of inflammatory cytokine levels, and microbiome analysis.', '1,25(OH)2D3 altered E. coli O157:H7-induced reductions in transepithelial electrical resistance (P < .01), decreased permeability (P < .05), and preserved barrier integrity. Vitamin D-deficient mice challenged with C. rodentium demonstrated increased colonic hyperplasia and epithelial barrier dysfunction (P < .0001 and P < .05, respectively). Vitamin D deficiency resulted in an altered composition of the fecal microbiome both in the absence and presence of C. rodentium infection.",
            "output": [
                "Does vitamin D deficiency promote epithelial barrier dysfunction and intestinal inflammation?"
            ]
        },
        {
            "id": "task847-57caf84da93649dda7d78963af295e47",
            "input": "Type 2 diabetes and associated co-morbidities run epidemic waves worldwide. Since pathophysiological constellations are individual and display a wide spread of dysmetabolic profiles personalized health care assessments start to emerge. Therefore, we established a specific in silico assessment tool targeting metabolic characterizations individually.', 'Values obtained from oral glucose and intraperitoneal insulin tolerance tests performed on pkb\u03b1(-/-) mice (KO) as well as age- and gender-matched controls (WT) were analysed using our established in silico model.', 'Generally, male pkb\u03b1(-/-) mice (KO) presented significantly increased insulin sensitivity at an age of 6 months compared with age-matched WTs (p = 0.036). Female KO and WT groups displayed improved glucose sensitivities compared with age-matched males (for WT p \u2264 0.011).",
            "output": [
                "Does novel individual metabolic profile characterize the protein kinase B-alpha ( pkb\u03b1-/- ) in vivo model?"
            ]
        },
        {
            "id": "task847-8b4ea213b65647ddaf1ae55119d534fa",
            "input": "This study tested the hypothesis that pioglitazone reduces endothelin-1 activity in the forearm vasculature in non-diabetic patients with hypertension or hypercholesterolemia and variable degrees of insulin resistance.', 'We conducted a single center, randomized, double-blind, placebo controlled, cross-over trial in 80 patients with either hypertension or hypercholesterolemia and further classified as insulin-sensitive or insulin-resistant based on a published insulin sensitivity index. Participants received pioglitazone 45 mg daily or matching placebo for eight weeks. The main endpoint was the change in forearm vascular endothelin-1 activity, as assessed by intra-arterial infusion of the endothelin type A receptor blocker BQ-123, measured at the end of each 8-week treatment period.', 'Pioglitazone lowered plasma insulin (P < 0.001), improved insulin sensitivity (P < 0.001), increased HDL (P < 0.001), and reduced triglycerides (P = 0.003), free fatty acids (P = 0.005), and C-reactive protein (P = 0.001). However, pioglitazone did not affect the vasodilator response to BQ-123 in the whole group (P = 0.618) and in the diagnosis or insulin sensitivity subgroups. Hence, in non-diabetic patients with hypertension or hypercholesterolemia, PPAR\u03b3 activation with pioglitazone does not affect endothelin-1 activity, despite enhancing insulin sensitivity and reducing plasma insulin and C-reactive protein levels.",
            "output": [
                "Does pPAR\u03b3 activation affect endothelin activity in non-diabetic patients with hypertension or hypercholesterolemia?"
            ]
        },
        {
            "id": "task847-302d9a41fa3d4e268db6bd2e06864116",
            "input": "This study assesses the relationship between septal curvature and mean pulmonary artery pressure and indexed pulmonary vascular resistance in children with pulmonary hypertension. We hypothesized that septal curvature could be used to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics.', 'Fifty patients with a median age of 6.7 years (range, 0.45-16.5 years) underwent combined cardiac catheterization and cardiovascular magnetic resonance. The majority had idiopathic pulmonary arterial hypertension (n=30); the remaining patients had pulmonary hypertension associated with repaired congenital heart disease (n=17) or lung disease (n=3). Mean pulmonary artery pressure and pulmonary vascular resistance were acquired at baseline and during vasodilation. Septal curvature was measured using real-time cardiovascular magnetic resonance. There was a strong correlation between mean pulmonary artery pressure and SCmin at baseline and during vasodilator testing (r=-0.81 and -0.85, respectively; P<0.01). A strong linear relationship also existed between pulmonary vascular resistance and minimum septal curvature indexed to cardiac output both at baseline and during vasodilator testing (r=-0.88 and -0.87, respectively; P<0.01). Change in septal curvature metrics moderately correlated with absolute change in mean pulmonary artery pressure and pulmonary vascular resistance, respectively (r=0.58 and -0.74; P<0.01). Septal curvature metrics were able to identify vasoresponders with a sensitivity of 83% (95% confidence interval, 0.36-0.99) and a specificity of 91% (95% confidence interval, 0.77-0.97), using the Sitbon criteria. Idiopathic pulmonary arterial hypertension subgroup analysis revealed 3 responders with \u0394SCmin values of 0.523, 0.551, and 0.568. If the middle value of 0.551 is taken as a cutoff, the approximate sensitivity would be 67% and the specificity would be 93%.",
            "output": [
                "Does real-time magnetic resonance assessment of septal curvature accurately track acute hemodynamic changes in pediatric pulmonary hypertension?"
            ]
        },
        {
            "id": "task847-4fe31a810108480c9e50c47d77b9a854",
            "input": "The prognosis of patients with severe aortic stenosis, low aortic gradient and preserved ejection fraction is controversial. Our study analyzed the prognosis of these patients and its relation to pressure gradient and aortic valve flow.', 'We performed a retrospective cohort study of 363 consecutive patients with severe aortic stenosis and preserved ejection fraction, divided into 4 groups, based on the presence of a systolic volume index greater or lower than 35 mL/m(2) and the presence of a mean aortic gradient greater or lower than 40 mmHg. Group I: normal flow, high gradient (n=169, 47%); group II: normal flow, low gradient (n=98, 27%); group III: low flow, high gradient (n=54, 15%), and group IV: low flow, low gradient (n=42, 12%). The primary endpoint was overall mortality.', 'Independent risk factors for mortality were age (hazard ratio=1.04; 95% confidence interval, 1.01-1.08) and atrial fibrillation (hazard ratio=2.21; 95% confidence interval, 1.24-3.94). Surgical treatment was associated with longer survival in all groups (hazard ratio=0.25; 95% confidence interval: 0.13-0.49). Mortality was higher in patients with low flow than in those with with normal flow (26.6% vs 13.6%; P=.004). The most favorable mean prognosis was found in group II (hazard ratio=0.4; 95% confidence interval, 0.2-0.9).",
            "output": [
                "Is systolic volume index by Doppler echocardiography an useful marker for stratification and prognostic evaluation in patients with severe aortic stenosis and preserved ejection fraction?"
            ]
        },
        {
            "id": "task847-e645b6e3ba2146b9841538446a310854",
            "input": "Eprosartan is an angiotensin II receptor antagonist used as an antihypertensive. We sought to evaluate the regional effect of Eprosartan on postinfarct ventricular remodeling and myocardial function in an isolated swine working heart model of ischemia-reperfusion injury.', '22 swine hearts were perfused with the Langendorff perfusion apparatus under standard experimental conditions. Myocardial ischemia was induced by a 10-min left anterior descending artery ligation. Hearts were reperfused with either saline (control group, n=11), or Eprosartan (treatment group, n=11). Left ventricular pressure (LVP) and regional heart parameters such as intramyocardial pressure (IMP), wall thickening rate (WTh), and pressure-length-loops (PLL) were measured at baseline and after 30 min of reperfusion.', 'Measured parameters were statistically similar between the 2 groups at baseline. The administration of Eprosartan led to a significantly better recovery of IMP and WTh: 44.4\u00b12.5 mmHg vs. 51.2\u00b13.3 mmHg, p<0.001 and 3.8\u00b10.4 \u00b5m vs. 4.4\u00b10.3 \u00b5m, p=0.001, respectively. PLL were also significantly higher in the treatment group following reperfusion (21694\u00b13259 units vs. 31267\u00b13429 units, p<0.01). There was no difference in the LVP response to Eprosartan versus controls (63.6\u00b13.0 mmHg vs. 62.5\u00b13.1 mmHg, p=0.400).",
            "output": [
                "Does eprosartan improve cardiac function in swine working heart model of ischemia-reperfusion injury?"
            ]
        },
        {
            "id": "task847-fa66431f797e4ddb89230452818947f6",
            "input": "The increasing global threat of Dengue demands new and easily applicable vector control methods. Ovitraps provide a low-tech and inexpensive means to combat Dengue vectors. Here we describe the development and optimization process of a novel contamination device that targets multiple life-stages of the Aedes aegypti mosquito. Special focus is directed to the diverse array of control agents deployed in this trap, covering adulticidal, larvicidal and autodissemination impacts.', 'Different trap prototypes and their parts are described, including a floater to contaminate alighting gravid mosquitoes. The attractiveness of the trap, different odor lures and floater design were studied using fluorescent powder adhering to mosquito legs and via choice tests. We demonstrate the mosquitocidal impacts of the control agents: a combination of the larvicide pyriproxyfen and the adulticidal fungus Beauveria bassiana. The impact of pyriproxyfen was determined in free-flight dissemination experiments. The effect on larval development inside the trap and in surrounding breeding sites was measured, as well as survival impacts on recaptured adults.', 'The developmental process resulted in a design that consists of a black 3 Liter water-filled container with a ring-shaped floater supporting vertically placed gauze dusted with the control agents. On average, 90% of the mosquitoes in the fluorescence experiments made contact with the gauze on the floater. Studies on attractants indicated that a yeast-containing tablet was the most attractive odor lure. Furthermore, the fungus Beauveria bassiana was able to significantly increase mortality of the free-flying adults compared to controls. Dissemination of pyriproxyfen led to >90% larval mortality in alternative breeding sites and 100% larval mortality in the trap itself, against a control mortality of around 5%.",
            "output": [
                "Does development and evaluation of a novel contamination device that target multiple life-stages of Aedes aegypti?"
            ]
        },
        {
            "id": "task847-8c0c2310dde54234bb431b70610eb135",
            "input": "The main complication of Kawasaki disease is the Coronary Artery (CA) involvement and long term follow up of patients depends on the severity of coronary arterial aneurysms, ischemia, and thrombosis. Early diagnosis of these complications can lead to a more desirable outcome for patients. Myocardial ischemia can prolong QT dispersion and increase the risk of cardiac arrhythmias as well as sudden cardiac arrests. Also, T wave peak-to-end (Tp-Te) interval dispersion, which provides a valuable index of transmural dispersion of repolarization, can trigger the arrhythmia.', \"We evaluated the non-corrected QT interval dispersion (QTD) and the corrected QT (QTc) dispersion and measured Tp-Te interval dispersion in 49 Iranian children (28 males and 21 females) with the diagnosis of Kawasaki disease (KD) in the acute phase and 49 age-matched controls in a prospective study from 2009 to 2012. Student's t-test and Pearson correlation were used to analyze the data. All the statistical analyses were performed through the SPSS 16. Besides, P<0.05 was considered as statistically significant.\", 'Patients with KD had significantly longer QTc dispersion (0.099\u00b10.055 s versus. 0.040\u00b10.018 s; P<0.001), non-corrected QT dispersion (0.075\u00b10.046 versus 0.042\u00b10.019; P<0.001), and Tp-Te dispersion (0.047\u00b10.054 versus 0.022\u00b10.011; P=0.015). The patients with elevation in white blood cell count (above 15000) had a statistically significant increased in QTD (P=0.011). No significant correlation was found between coronary involvement and repolarization indexes.",
            "output": [
                "Do qT Dispersion and T Wave Peak-to-end Interval Dispersion in Children with Kawasaki Disease?"
            ]
        },
        {
            "id": "task847-ec827fae2b4e4b32a69123b4dbe9bb8c",
            "input": "Physicians refer proteinuric patients to kidney biopsy in order to clarify the issue of underlying renal disease. We compared kidney biopsy results with classical outcome parameters in a large cohort of patients with biopsy proven glomerulonephritis (GN).', 'In a retrospective analysis, 2687 patients with different forms of GN from 123 Austrian centres were investigated. Patient characteristics, the diagnosis of GN and its respective subtype and clinical symptoms such as arterial hypertension, haematuria, amount of proteinuria and estimated glomerular filtration rate (eGFR) were tested for their association with all-cause mortality and progression to end-stage renal disease (ESRD).', \"During a median follow-up of 129\u00b79\\xa0months (IQR 89\u00b76; 177\u00b77), 688 patients (25\u00b76%) died and 718 patients required dialysis (29\u00b74%). In multivariate Cox's regression analysis age (HR 1\u00b706), female sex (HR 0\u00b771), eGFR (HR 0\u00b774), the diagnosis of GN and its subtypes predicted patient survival (all P\\xa0<\\xa00\u00b701), whereas the amount of proteinuria was not associated with patient survival. The incidence of progression to ESRD was associated with female sex (HR 0\u00b771), eGFR (HR 0\u00b765), amount of proteinuria (HR 1\u00b715) and the diagnosis of GN and its subtypes (all P\\xa0<\\xa00\u00b701). Nephrotic or nephritic syndromes were not associated with patient survival or progression to ESRD and did not add further predictive value to outcome of GN.",
            "output": [
                "Does kidney biopsy result versus clinical parameters on mortality and ESRD progression in 2687 patients with glomerulonephritis?"
            ]
        },
        {
            "id": "task847-8069b37c3aaa44268f079746929b50d0",
            "input": "Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments.', 'ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle.",
            "output": [
                "Does visual gene-network analysis reveal the cancer gene co-expression in human endometrial cancer?"
            ]
        },
        {
            "id": "task847-a7ca680a25fa4d51913cdfb880210457",
            "input": "The presence of silent cerebral infarction (SCI) increases the risk of transient ischaemia attack, symptomatic stroke, cardiovascular disease and dementia. Mean platelet volume (MPV) is a surrogate marker of activated platelets and is considered a link between inflammation and thrombosis. In addition, MPV is a risk predictor for cardiovascular disease, stroke and overall vascular mortality.', 'The purpose of the study was to assess the MPV levels in SCI patients.', 'A cross-sectional study was conducted to evaluate the association between MPV and SCI in 2215 subjects (1385 men and 830 women).', 'The participants with SCI had higher MPV levels than those without SCI (10.4 \u00b1 1.3\\u2009fL vs. 9.2 \u00b1 1.2\\u2009fL; P < 0.001). Moreover, the subjects with a high MPV had a higher prevalence of SCI. Multivariate logistic regression analyses revealed that the odds ratios and 95% confidence intervals for SCI according to MPV quartiles were 1.000, 2.131 (1.319-3.444), 3.015 (1.896-4.794), 7.822 (4.874-12.554) respectively (P < 0.001).",
            "output": [
                "Is elevated mean platelet volume associated with silent cerebral infarction?"
            ]
        },
        {
            "id": "task847-1041c444c99545b7bc1a4026fa6050be",
            "input": "To study short-term results and clinical application of Tri-lock BPS in total hip arthoplasty.', 'From May 2010 to July 2011, 32 hips in 31 patients (18 males and 13 females, ranging in age from 50 to 77 years old, with an average of 60.5 years old) were treated by total hip arthroplasty with Tri-lock BPS, including 8 patients with osteonecrosis (ON), 13 patients with fresh femoral neck fracture, 10 patients with developmental dysplasia of the hip (DDH). The therapeutic effects were evaluated by self assessment form, preoperative and postoperative Harris hip score, radiographs, Engh score and bone in growth of femoral side described by Gruen. Based on the short-term results,its design characteristic and clinical properties were analyzed.', 'All the incisions healed well and there were no complications such as femoral fracture, infection, dislocation and neurovascular injuries. All the patients were followed up with an average time of 12.2 months (ranged, 10 to 14 months). All the joints had good or excellent clinical results. The Harris score increased from preoperative 38.3 +/- 4.9 to 92.5 +/- 11.2 at the latest follow-up (t = 27.53, P < 0.01). Radiographically, the positions of the prostheses were normal,the average limbs length and femoral eccentricity recovered to normal. X-ray of the hips showed that the femoral stem prosthesis was in line with good initial fixed standard. At 3 months after surgery, X-ray of the hips showed that bone in growth in Gruen II and VI of femoral side.",
            "output": [
                "Do [ Clinical apprehension on application of Tri-lock BPS total hip arthroplasty ]?"
            ]
        },
        {
            "id": "task847-a3683c53725f4f14b1dbf381e4693aa7",
            "input": "Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients.', 'The effects of allogeneic umbilical cord-derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC-mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation.', 'Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-\u03b3 (IFN\u03b3), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow-derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFN\u03b3 and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients.",
            "output": [
                "Is a CD8 T cell/indoleamine 2,3-dioxygenase axis required for mesenchymal stem cell suppression of human systemic lupus erythematosus?"
            ]
        },
        {
            "id": "task847-9bf0bc232f6c43c592b747043b1db8bf",
            "input": "Cognitive remediation (CR) aims primarily to improve cognition and functional outcomes. However, a limited number of studies reported a positive effect on symptoms. This limited effect may be because the symptom clusters considered are too broad and heterogeneous. This study explores, for the first time, the effect of CR on five empirically defined symptom dimensions of schizophrenia.', 'Participants were patients with schizophrenia taking part in a randomised controlled trial comparing CR plus treatment as usual (CR, N=43) to treatment as usual (TAU, N=42). All participants were assessed at baseline and 14-weeks (i.e. at the conclusion of treatment for the CR group) with the Positive and Negative Symptoms Scale (PANSS). Five symptom dimensions were derived from the PANSS scores: Positive (POS), Negative (NEG), Disorganised (DIS), Excited (EXC) and Emotional Distressed (EMD).', 'After CR, the therapy group had a significant reduction in DIS and NEG symptom dimensions compared to the TAU group. The traditional PANSS factors showed no effect of CR on symptoms.",
            "output": [
                "Is it all in the factors : effects of cognitive remediation on symptom dimensions?"
            ]
        },
        {
            "id": "task847-1dcac42d3032487c9571565465084b7b",
            "input": "Fibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead. Studies of intraosseous infusion of coagulation factor concentrates are limited. We investigated in vivo recovery following intraosseous administration of fibrinogen concentrate and compared the results with intravenous administration.', 'This study was performed on 12 pigs (mean [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and fluid replacement with balanced crystalloid solution, intraosseous (n = 6) administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in the proximal tibia was compared with intravenous (n = 6) administration of the same dose (fibrinogen infusion time approximately 5 minutes in both groups). The following laboratory parameters were assessed: blood cell count, prothrombin time index, activated partial thromboplastin time, and plasma fibrinogen concentration (Clauss assay). Coagulation status was also assessed by thromboelastometry.', 'All tested laboratory parameters were comparable between the intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes after fibrinogen concentrate administration. In vivo recovery of fibrinogen was also similar in the two groups (89% [23%] and 91% [22%], respectively). There were no significant between-group differences in any of the thromboelastometric parameters. Histologic examination indicated no adverse effects on the tissue surrounding the intraosseous administration site.",
            "output": [
                "Is recovery of fibrinogen concentrate after intraosseous application equivalent to the intravenous route in a porcine model of hemodilution?"
            ]
        },
        {
            "id": "task847-cbc09878ed524c049c4cdd5b79a8d131",
            "input": "Information about malaria risk factors at high altitudes is scanty. Understanding the risk factors that determine the risk of malaria transmission at high altitude villages is important to facilitate implementing sustainable malaria control and prevention programs.', 'An unmatched case control study was conducted among patients seeking treatment at health centers in high altitude areas. Either microscopy or rapid diagnostic tests were used to confirm the presence of plasmodium species. A generalized linear model was used to identify the predictors of malaria transmission in high altitude villages.', 'Males (AOR\\u200a=\\u200a3.11, 95%CI: 2.28, 4.23), and those who traveled away from the home in the previous month (AOR\\u200a=\\u200a2.01, 95% CI: 1.56, 2.58) were strongly associated with presence of malaria in high altitude villages. Other significant factors, including agriculture in occupation (AOR\\u200a=\\u200a1.41, 95% CI: 1.05, 1.93), plants used for fencing (AOR\\u200a=\\u200a1.70, 95% CI: 1.18, 2.52) and forests near the house (AOR\\u200a=\\u200a1.60, 95% CI: 1.15, 2.47), were found predictors for malaria in high altitude villages.",
            "output": [
                "Are men traveling away from home more likely to bring malaria into high altitude villages , northwest Ethiopia?"
            ]
        },
        {
            "id": "task847-98992dd5ad944cb785f7a6471ade7d7e",
            "input": "The transcription factor GATA3 is a favorable prognostic indicator in estrogen receptor-\u03b1 (ER\u03b1)-positive breast tumors in which it participates with ER\u03b1 and FOXA1 in a complex transcriptional regulatory program driving tumor growth. GATA3 mutations are frequent in breast cancer and have been classified as driver mutations. To elucidate the contribution(s) of GATA3 alterations to cancer, we studied two breast cancer cell lines, MCF7, which carries a heterozygous frameshift mutation in the second zinc finger of GATA3, and T47D, wild-type at this locus.', 'Immunofluorescence staining and subcellular fractionation were employed to verify cellular localization of GATA3 in T47D and MCF7 cells. To test protein stability, cells were treated with translation inhibitor, cycloheximide or proteasome inhibitor, MG132, and GATA3 abundance was measured over time using immunoblot. GATA3 turn-over in response to hormone was determined by treating the cells with estradiol or ER\u03b1 agonist, ICI 182,780. DNA binding ability of recombinant GATA3 was evaluated using electrophoretic mobility shift assay and heparin chromatography. Genomic location of GATA3 in MCF7 and T47D cells was assessed by chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq).', 'GATA3 localized in the nucleus in T47D and MCF7 cells, regardless of the mutation status. The truncated protein in MCF7 had impaired interaction with chromatin and was easily released from the nucleus. Recombinant mutant GATA3 was able to bind DNA to a lesser degree than the wild-type protein. Heterozygosity for the truncating mutation conferred protection from regulated turnover of GATA3, ER\u03b1 and FOXA1 following estrogen stimulation in MCF7 cells. Thus, mutant GATA3 uncoupled protein-level regulation of master regulatory transcription factors from hormone action. Consistent with increased protein stability, ChIP-seq profiling identified greater genome-wide accumulation of GATA3 in MCF7 cells bearing the mutation, albeit with a similar distribution across the genome, comparing to T47D cells.",
            "output": [
                "Does breast tumor specific mutation in GATA3 affect physiological mechanisms regulating transcription factor turnover?"
            ]
        },
        {
            "id": "task847-6b34b97f4eba49a2bcf49f5e92c74795",
            "input": "To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia (ALL).', 'We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort (n = 48), receiver operating characteristic (ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort (n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed.', 'ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival (LFS) and event-free survival (EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR-ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease (MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR-ABL fusion.",
            "output": [
                "Does e2F3a gene expression have prognostic significance in childhood acute lymphoblastic leukemia?"
            ]
        },
        {
            "id": "task847-30a130b524de4dab8c3dbad98df5ee5d",
            "input": "Angiogenin undergoes nuclear translocation and stimulates ribosomal RNA transcription in both endothelial and cancer cells. Consequently, angiogenin has a dual effect on cancer progression by inducing both angiogenesis and cancer cell proliferation. The aim of this study was to assess whether neamine, a blocker of nuclear translocation of angiogenin, possesses antitumor activity toward oral cancer.', 'The antitumor effect of neamine on oral cancer cells was examined both in vitro and in vivo.', 'Neamine inhibited the proliferation of HSC-2, but not that of SAS oral cancer cells in vitro. Treatment with neamine effectively inhibited growth of HSC-2 and SAS cell xenografts in athymic mice. Neamine treatment resulted in a significant decrease in tumor angiogenesis, accompanied by a decrease in angiogenin- and proliferating cell nuclear antigen-positive cancer cells, especially of HSC-2 tumors.",
            "output": [
                "Does neamine inhibit oral cancer progression by suppressing angiogenin-mediated angiogenesis and cancer cell proliferation?"
            ]
        },
        {
            "id": "task847-9b7a837b2f064050b4d133eb8b22ad9c",
            "input": "NOTCH-regulated ankyrin repeat protein (NRARP) has been implicated in crosstalk between NOTCH and wingless-type mouse mammary tumor virus integration site (WNT) signals during development. Our study aimed to clarify its role in breast cancer cells.', 'Public microarray data were used to analyze gene expression in human and rat breast cancer. A short interfering RNA was introduced into MCF7 and T47D human breast cancer cells for NRARP silencing. Gene expression was analyzed by quantitative polymerase chain reaction.', 'The NRARP transcript was commonly overexpressed in various rat mammary cancer models. In addition, a subset of human breast cancer also expressed high levels of NRARP transcript, which correlated positively with up-regulation of cell proliferation-related genes. Silencing of NRARP suppressed the growth of MCF7 and T47D cells and lowered the expression of cell cycle-related genes in MCF7 cells.",
            "output": [
                "Is overexpression of NOTCH-regulated ankyrin repeat protein associated with breast cancer cell proliferation?"
            ]
        },
        {
            "id": "task847-b7ee04a89f58417e8f90cf47f1159e61",
            "input": "The main objective of the present study was the investigation of possible influence of lens opacification on macular pigment optical density (MPOD) measurements.', 'Eighty-six eyes of 64 patients (mean age 73.4 \u00b1 8.3 years) were included in the study. MPOD was prospectively measured using the one-wavelength reflection method (Visucam500, Carl Zeiss Meditec AG) before and after cataract extraction, with implantation of a blue-light filtering intraocular lens (AlconSN60WF). The median of the maximum optical density (MaxOD) and the median of the mean optical density (MeanOD) measurements of macular pigment across the subject group were evaluated.', 'Statistically significant differences were noticed between pre-operative and post-operative measurements, the absolute values were generally lower after cataract extraction. The following median (lower/upper quartile) differences across the group were determined: MaxOD -33.8 % (-46.2 to -19.1 %), MeanOD -44.0 % (-54.6 to -26.6 %). Larger changes were observed in elderly patients [<70 years of age (n\\u2009=\\u200925 eyes): MaxOD -13.4 % (-20.5 to 3.6 %), MeanOD -23.6 % (-30.5 to -15.3 %) versus patients \u226570 years (n\\u2009=\\u200961 eyes) MaxOD -40.5 % (-53.2 to -30.1 %), MeanOD -47.2 % (-57.8 to -40.1 %)] and in patients with progressed stage of cataract. MaxOD for lens opacification grade 1 (n\\u2009=\\u20099 eyes): -27.4 % (-42.1 to -19.6 %), grade 2 (n\\u2009=\\u200926 eyes): -35.0 % (-44.2 to -25.3 %), grade 3 (n\\u2009=\\u200921 eyes): -34.4 % (-45.4 to -11.4 %), grade 4 (n\\u2009=\\u200925 eyes): -32.6 % (-53.2 to -6.4 %), and grade 5 (n\\u2009=\\u20095 eyes): -53.5 % (-61.7 to -38.7 %) and MeanOD for cataract stage 1 (n\\u2009=\\u20099 eyes): -42.6 % (-46.0 to -26.0 %), stage 2 (n\\u2009=\\u200926 eyes): -44.1 % (-51.8 to -26.2 %), stage 3 (n\\u2009=\\u200921 eyes): -45.7 % (-54.7 to -24.7 %), stage 4 (n\\u2009=\\u200925 eyes): -39.5 % (-59.4 to -26.1 %), and stage 5 (n\\u2009=\\u20095 eyes): -57.0 % (-66.1 to -51.4 %).",
            "output": [
                "Does macular pigment optical density measurements by one-wavelength reflection photometry -- influence of cataract surgery on the measurement result?"
            ]
        },
        {
            "id": "task847-55c6b1d6fa354388994e0ef6a3566098",
            "input": "Contrast-induced acute kidney injury (CI-AKI) occurs after the administration of intravenous iodinated contrast agents. Oxidative stress has been proposed as one of the most important mechanisms in the pathogenesis of CI-AKI. The objective of this study was to investigate the antioxidant effect of the extract from Phyllanthus emblica (PE) in preventing CI-AKI.', 'Male Sprague Dawley rats were subjected into eight groups, were given water (control) or PE extract (125 or 250 or 500 mg/kg/day) for 5 days before the induction of CI-AKI. Renal function and oxidative stress markers; malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activity were determined in plasma and renal tissue. Kidney sections were performed for histopathological examination.', 'In the contrast media (CM) group, increases in blood urea nitrogen and serum creatinine were demonstrated which correlated with severity of tubular necrosis, peritubular capillary congestion and interstitial edema. Moreover, an increase in MDA and a decrease in TAC SOD and CAT activity in CM group were significantly changed when compared with the control (P<0.05). In contrast, CI-AKI-induced rats administrated with PE extract 250 and 500 mg/kg/day significantly preserved renal function and attenuated the severity of pathological damage (P<0.05) as well as significantly lower MDA and higher TAC, SOD and CAT than the CM group (P<0.05).",
            "output": [
                "Does antioxidant effect of Phyllanthus emblica extract prevent contrast-induced acute kidney injury?"
            ]
        },
        {
            "id": "task847-b1c0bc7051924eddaa29311fd8151d70",
            "input": "A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the NQO1 gene in the risk for MS in the Spanish Caucasian population.', 'We analyzed allelic and genotypic frequency of NQO1 rs1800566 in 290 patients with MS and 310 healthy controls, using TaqMan Assays.', 'NQO1 rs1800566 allelic and genotypic frequencies did not differ significantly between MS patients and controls, and were unrelated with age of onset of MS, gender, and clinical type of MS.",
            "output": [
                "Is nQO1 gene rs1800566 variant associated with risk for multiple sclerosis?"
            ]
        },
        {
            "id": "task847-0335da4f20b2485eb8a5da0f8a03bdfa",
            "input": "To determine, for the WHO algorithm for point-of-care diagnosis of HIV infection, the agreement levels between paediatricians and non-physician clinicians, and to compare sensitivity and specificity profiles of the WHO algorithm and different CD4 thresholds against HIV PCR testing in hospitalised Malawian infants.', 'In 2011, hospitalised HIV-exposed infants <12 months in Lilongwe, Malawi, were evaluated independently with the WHO algorithm by both a paediatrician and clinical officer. Blood was collected for CD4 and molecular HIV testing (DNA or RNA PCR). Using molecular testing as the reference, sensitivity, specificity and positive predictive value (PPV) were determined for the WHO algorithm and CD4 count thresholds of 1500 and 2000 cells/mm(3) by paediatricians and clinical officers.', 'We enrolled 166 infants (50% female, 34% <2 months, 37% HIV infected). Sensitivity was higher using CD4 thresholds (<1500, 80%; <2000, 95%) than with the algorithm (physicians, 57%; clinical officers, 71%). Specificity was comparable for CD4 thresholds (<1500, 68%, <2000, 50%) and the algorithm (paediatricians, 55%, clinical officers, 50%). The positive predictive values were slightly better using CD4 thresholds (<1500, 59%, <2000, 52%) than the algorithm (paediatricians, 43%, clinical officers 45%) at this prevalence.",
            "output": [
                "Does cD4 count outperform World Health Organization clinical algorithm for point-of-care HIV diagnosis among hospitalised HIV-exposed Malawian infants?"
            ]
        },
        {
            "id": "task847-213c134c19d743358fbe4e64d22a88a2",
            "input": "Cardiac overexpression of the \u03b2-adrenoreceptor (\u03b2AR)-coupled stimulatory G-protein subunit G\u03b1s enhances inotropic responses to adrenergic stimulation and improves survival in mice under \u03b2AR blockade. The authors recently identified three common haplotypes in the GNAS gene encoding G\u03b1s, with the greatest G\u03b1s protein expression and signal transduction in haplotype *3 carriers and less in haplotype *2 and *1 carriers. The authors tested the hypothesis that these GNAS variants result in altered mortality in patients after coronary artery bypass graft surgery, particularly in those receiving \u03b2AR blockade.', 'This prospective analysis included 1,627 European ancestry patients undergoing primary coronary artery bypass graft surgery. Patients were genotyped for two GNAS haplotype tagging single-nucleotide polymorphisms defining three major haplotypes. Up to 5-yr all-cause mortality was estimated using a Cox proportional hazard model; hazard ratios and 95% CIs were calculated while adjusting for demographics, clinical covariates, and the new EuroSCORE II.', 'Univariate analysis revealed haplotype-dependent 5-yr mortality rates (*1/*1: 18.9%, *2/*1: 13.7%, *2/*2: 9.3%, *3/*1: 10.6%, *3/*2: 9.1%, and *3/*3: 9.6%; P = 0.0006). After adjustment for other predictors of death, homozygote haplotype *1 carriers showed a doubled risk for death (hazard ratio, 2.2; 95% CI, 1.2 to 3.8; P = 0.006). Considering only patients receiving \u03b2AR blockers (n = 1,267), the adjusted risk of death even tripled (hazard ratio, 3.0; 95% CI, 1.5 to 6.1; P = 0.002).",
            "output": [
                "Do gNAS gene variants affect \u03b2-blocker-related survival after coronary artery bypass grafting?"
            ]
        },
        {
            "id": "task847-89b1acab8ab548ac89775e1e0aa7bea8",
            "input": "The traditional management of complex penetrating duodenal trauma (PDT) has been the use of elaborate temporizing and complex procedures such as the pyloric exclusion and duodenal diverticulization. We sought to determine whether a simplified surgical approach to the management of complex PDT injuries improves clinical outcome.', 'A retrospective review of all consecutive PDT from 2003 to 2012 was conducted. Patients were divided into three groups according to a simplified surgical algorithm devised following the local experience at a regional Level I trauma center. Postoperative duodenal leaks were drained externally either via traditional anterior drainage or via posterior \"retroperitoneal laparostomy\" as an alternate option.', 'There were 44 consecutive patients with PDT, and 41 of them (93.2%) were from gunshot wounds. Seven patients were excluded owing to early intraoperative death secondary to associated devastating traumatic injuries. Of the remaining 36 patients, 7 (19.4%) were managed with single-stage primary duodenal repair with definitive abdominal wall fascial closure (PDR + NoDC group). Damage-control laparotomy was performed in 29 patients, (80.5%) in which primary repair was performed in 15 (51.7%) (PDR + DC group), and the duodenum was over sewn and left in discontinuity in 14 (48.3%). Duodenal reconstruction was performed after primary repair in 2 of 15 cases and after left in discontinuity in 13 of 14 cases (DR + DC group). The most common complication was the development of a duodenal fistula in 12 (33%) of 36 cases. These leaks were managed by traditional anterior drainage in 9 (75%) of 12 cases and posterior drainage by retroperitoneal laparostomy in 3 (25%) of 12 cases. The duodenal fistula closed spontaneously in 7 (58.3%) of 12 cases. The duodenum-related mortality rate was 2.8%, and the overall mortality rate was 11.1%.",
            "output": [
                "Is complex penetrating duodenal injuries : less better?"
            ]
        },
        {
            "id": "task847-c80e3870fecf42f7813f85cabfc90c46",
            "input": "Computed tomography (CT) is an imaging modality involving ionizing radiation. The presence of \u03b3-H2AX foci after low to moderate ionizing radiation exposure has been demonstrated; however it is unknown whether very low ionizing radiation exposure doses from CT exams can induce \u03b3-H2AX formation in vivo in young children.', 'To test whether very low ionizing radiation doses from CT exams can induce lymphocytic \u03b3-H2AX foci (phosphorylated histones used as a marker of DNA damage) formation in vivo in young children.', 'Parents of participating children signed a consent form. Blood samples from three children (ages 3-21\\xa0months) undergoing CT exams involving very low blood ionizing radiation exposure doses (blood doses of 0.22-1.22\\xa0mGy) were collected immediately before and 1\\xa0h post CT exams. Isolated lymphocytes were quantified for \u03b3-H2AX foci by a technician blinded to the radiation status and dose of the patients. Paired t-tests and regression analyses were performed with significance levels set at P\\u2009<\\u20090.05.', 'We observed a dose-dependent increase in \u03b3-H2AX foci post-CT exams (P\\u2009=\\u20090.046) among the three children. Ionizing radiation exposure doses led to a linear increase of foci per cell in post-CT samples (102% between lowest and highest dose).",
            "output": [
                "Are \u03b3-H2AX foci increased in lymphocytes in vivo in young children 1 h after very low-dose X-irradiation : a pilot study?"
            ]
        },
        {
            "id": "task847-2672d5dba271436bb331279d03622d3a",
            "input": "Hemodialysis (HD) patients are exposed to a high risk of death. Nutritional status has been recognized as a key factor for patient survival. Nutritional markers have been shown to improve after HD onset. In this study we have analyzed the dynamics of target weight (TGW) change and the evolution of other nutritional parameters during the first year of HD treatment and their influence on patients' outcomes.\", 'We have analyzed a retrospective cohort of incident patients starting HD therapy between January 2000 and January 2009, and studied the values and changes in TGW, interdialytic weight gain (IDWG), predialysis systolic blood pressure, serum albumin, protein intake, C-reactive protein (CRP) from the start and first week (W1), W8, W12, W26 and W52 in patients who survived the first year of therapy. We have analyzed the relationship between TGW changes with other nutritional parameters and the patient survival.', 'Among the cohort including 363 patients starting HD therapy, 251 (age 65.8 \u00b1 14.8 years, 93 female/158 male, diabetes 36%) survived at least 1 year after dialysis onset and were followed for 44.9 months. During the first 8 weeks, the TGW decreased by 6.5 \u00b1 5.6% (initial TGW change). The initial TGW change was correlated with IDWG at W12 and W26, and with changes in serum albumin and nPNA (normalized protein equivalent of nitrogen appearance) between HD W1 and W52 (respectively +7.8 and +11.4%). From W8 to W52, the TGW increased by +1.9 \u00b1 7.4% (secondary TGW change). The Kaplan-Meier analysis displayed a significantly better survival in patients above the median (+2.3%) of the secondary TGW change (respectively -3.6 \u00b1 5.2% and +7.6 \u00b1 4.5%). The two groups above and below this median were not different according to age, diabetes or cardiovascular event history but the patients above the median had a significant higher IDWG and protein intake. In the Cox model analysis the patient overall mortality was related to age (p < 0.0001), to the secondary TGW change (p = 0.0001), and to the CRP level at W52 (p < 0.0001).",
            "output": [
                "Is target weight gain during the first year of hemodialysis therapy associated with patient survival?"
            ]
        },
        {
            "id": "task847-4eb0f7d8f01e48c681adf8617cbce04d",
            "input": "To examine whether \u03b2-amyloid (A\u03b2) and APOE \u03b54 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN).', \"Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the contributions of APOE \u03b54 and A\u03b2 on longitudinal change over a median of 1.49 years were examined. Cognitive decline was assessed with the Mini-Mental State Examination (MMSE) and Logical Memory (immediate and delayed recall scores).\", 'High A\u03b2 participants were more likely to be APOE \u03b54+ than low A\u03b2 participants. CNs who were both high A\u03b2 and APOE \u03b54+ showed greater decline in Logical Memory immediate recall (p < 0.087), Logical Memory delayed recall (p < 0.024), and MMSE (p < 0.034) compared to all other groups (low A\u03b2/APOE \u03b54-, low A\u03b2/APOE \u03b54+, and high A\u03b2/APOE \u03b54-). No other pairwise contrast was significant for any cognitive measure.",
            "output": [
                "Do amyloid and APOE \u03b54 interact to influence short-term decline in preclinical Alzheimer disease?"
            ]
        },
        {
            "id": "task847-5cb353ce20544dbca3dd50df31a8c9c4",
            "input": "Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer. Investigation of the mechanism of invasion and metastasis of lung SCC will be of great help for the development of meaningful targeted therapeutics. This study is intended to understand whether the activation of Hedgehog (Hh) pathway is involved in lung SCC, and whether activated Hh signaling regulates metastasis through epithelial-mesenchymal transition (EMT) in lung SCC.', 'Two cohorts of patients with lung SCC were studied. Protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. Protein expression levels in tissue specimens were scored and correlations were analyzed. Vismodegib and a Gli inhibitor were used to inhibit Shh/Gli activity, and recombinant Shh proteins were used to stimulate the Hh pathway in lung SCC cell lines. Cell migration assay was performed in vitro.', 'Shh/Gli pathway components were aberrantly expressed in lung SCC tissue samples. Gli1 expression was reversely associated with the expression of EMT markers E-Cadherin and \u03b2-Catenin in lung SCC specimens. Inhibition of the Shh/Gli pathway suppressed migration and up-regulated E-Cadherin expression in lung SCC cells. Stimulation of the pathway increased migration and down-regulated E-Cadherin expression in lung SCC cells.",
            "output": [
                "Does hedgehog/Gli promote epithelial-mesenchymal transition in lung squamous cell carcinomas?"
            ]
        },
        {
            "id": "task847-53f640a61bdf44a5b65492c1871fed37",
            "input": "To determine the impact of the time interval from the end of sperm preparation (TSP) to intrauterine insemination (IUI) on the outcome.', 'Prospective multicentre cohort study.', 'Seven French centers (assisted reproduction group in northeastern France, four academic centers, and three clinics).', 'Eight hundred sixty-two IUI cycles (709 patients) managed by gonadotropins were studied.', 'Cycles were stimulated by either FSH or hMG, and hCG was administrated when the leading follicle diameter measured >15 mm. IUIs were performed \u223c 36 hours after ovulation triggering.', 'Generalized linear mixed models for binary outcomes were used to model clinical pregnancy (CP) to assess the effect of TSP adjusted for other predictors (such as maternal age, semen quality, and indication of IUI treatment).', 'The TSP effect was significant, featuring an inverse U-shaped curve admitting an optimum interval of \u223c 40-80 minutes improving CP compared with other values. Other significant predictors were total motile spermatozoa inseminated, maternal age, and unexplained infertility.",
            "output": [
                "Is clinical success of intrauterine insemination cycles affected by the sperm preparation time?"
            ]
        },
        {
            "id": "task847-686b6b0e4a104352b1d5cf27df6105e8",
            "input": "The purpose of this study was to determine whether cycling time trial (TT) performance differs between hypobaric hypoxia (HH) and normobaric hypoxia (NH) at the same ambient PO2 (93\\xa0mmHg, 4,300-m altitude equivalent).', 'Two groups of healthy fit men were matched on physical performance and demographic characteristics and completed a 720-kJ time trial on a cycle ergometer at sea level (SL) and following approximately 2\\xa0h of resting exposure to either HH (n\\u2009=\\u20096, 20\\u2009\u00b1\\u20092\\xa0years, 75.2\\u2009\u00b1\\u200911.8\\xa0kg, mean\\u2009\u00b1\\u2009SD) or NH (n\\u2009=\\u20096, 21\\u2009\u00b1\\u20093\\xa0years, 77.4\\u2009\u00b1\\u20098.8\\xa0kg). Volunteers were free to manually increase or decrease the work rate on the cycle ergometer. Heart rate (HR), arterial oxygen saturation (SaO2), and rating of perceived exertion (RPE) were collected every 5\\xa0min during the TT, and the mean was calculated.', 'Both groups exhibited similar TT performance (min) at SL (73.9\\u2009\u00b1\\u20097.6 vs. 73.2\\u2009\u00b1\\u20098.2), but TT performance was longer (P\\u2009<\\u20090.05) in HH (121.0\\u2009\u00b1\\u200912.1) compared to NH (99.5\\u2009\u00b1\\u200918.1). The percent decrement in TT performance from SL to HH (65.1\\u2009\u00b1\\u200923.6%) was greater (P\\u2009<\\u20090.05) than that from SL to NH (35.5\\u2009\u00b1\\u200913.7%). The mean exercise SaO2, HR, and RPE during the TT were not different in HH compared to NH.",
            "output": [
                "Is cycling performance decrement greater in hypobaric versus normobaric hypoxia?"
            ]
        },
        {
            "id": "task847-0a7b25d8f3d9482c838f70b98e584b0f",
            "input": "Understanding what causes changes in the flux of free fatty acids (FFA) is important to elucidate the etiology of metabolic syndrome. The first aim of this study was to test whether or not hormones and the autonomic nervous system influence blood FFA levels. A secondary aim was to test by means of a multiple group path analysis whether the consumption of fermented red ginseng (FRG; Panax ginseng) would influence those causal relationships.', 'Ninety-three postmenopausal women (age 50-73\\xa0yr) were randomly divided into two groups. One group (44 women; age, 58.4\\xa0\u00b1\\xa05.9\\xa0yr; body mass index, 23.6\\xa0\u00b1\\xa02.5\\xa0kg/m(2)) was supplied placebo capsules and the other group (49 women, age 58.4\\xa0\u00b1\\xa05.5\\xa0yr; body mass index, 22.9\\xa0\u00b1\\xa02.4\\xa0kg/m(2)) was supplied FRG capsules. Both prior to and after the study (2\\xa0wk), blood samples were collected from the participants and several blood variables were measured and analyzed.', 'Squared multiple correlations of FFA were 0.699 in the placebo group and 0.707 in the FRG group. The unstandardized estimate of estradiol (E2) for FFA was 0.824 in both groups.",
            "output": [
                "Are free-fatty-acid-regulating effects of fermented red ginseng mediated by hormones and by the autonomic nervous system?"
            ]
        },
        {
            "id": "task847-911849af0664488aad958a5ef46b4d80",
            "input": "Three surgical approaches: cochleostomy (C), round window (RW), and extended round window (ERW); and two electrodes types: lateral wall (LW) and perimodiolar (PM), account for the vast majority of cochlear implantations. The goal of this study was to analyze the relationship between surgical approach and electrode type with final intracochlear position of the electrode array and subsequent hearing outcomes.', 'Comparative longitudinal study.', 'One hundred postlingually implanted adult patients were enrolled in the study. From the postoperative scan, intracochlear electrode location was determined and using rigid registration, transformed back to the preoperative computed tomography which had intracochlear anatomy (scala tympani and scala vestibuli) specified using a statistical shape model based on 10 microCT scans of human cadaveric cochleae. Likelihood ratio chi-square statistics were used to evaluate for differences in electrode placement with respect to surgical approach (C, RW, ERW) and type of electrode (LW, PM).', 'Electrode placement completely within the scala tympani (ST) was more common for LW than were PM designs (89% vs. 58%; P\\u2009<\\u20090.001). RW and ERW approaches were associated with lower rates of electrode placement outside the ST than was the cochleostomy approach (9%, 16%, and 63%, respectively; P\\u2009<\\u20090.001). This pattern held true regardless of whether the implant was LW or PM. When examining electrode placement and hearing outcome, those with electrode residing completely within the ST had better consonant-nucleus-consonant word scores than did patients with any number of electrodes located outside the ST (P\\u2009=\\u20090.045).",
            "output": [
                "Do impact of electrode design and surgical approach on scalar location and cochlear implant outcomes?"
            ]
        },
        {
            "id": "task847-fdba01ec7cb34ebfb38dfbbc98e0b440",
            "input": "Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT).', 'Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Livermean + [2 \u00d7 Liversd]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses.', 'Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm(3) or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses.",
            "output": [
                "Are baseline metabolic tumor volume and total lesion glycolysis associated with survival outcomes in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy?"
            ]
        },
        {
            "id": "task847-61d1362dcf844d01b879deb08a90357f",
            "input": "In HLA-B27-transgenic rats, the development of a disorder that mimics spondyloarthritis (SpA) is highly correlated with dendritic cell (DC) dysfunction. The present study was undertaken to analyze the underlying mechanisms of this via transcriptome analysis.', 'Transcriptome analysis of ex vivo-purified splenic CD103+CD4+ DCs from B27-transgenic rats and control rats was performed. Transcriptional changes in selected genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction. A meta-analysis of our rat data and published data on gene expression in macrophages from ankylosing spondylitis (AS) patients was further performed.', 'Interferon (IFN) signaling was the most significantly affected pathway in DCs from B27-transgenic rats; the majority of genes connected to IFN were underexpressed in B27-transgenic rats as compared to controls. This pattern was already present at disease onset, persisted over time, and was conserved in 2 disease-prone B27-transgenic rat lines. In DCs from B27-transgenic rats, we further found an up-regulation of suppressor of cytokine signaling 3 (which may account for reverse IFN signaling) and a down-regulation of interleukin-27 (a cytokine that opposes Th17 differentiation and promotes Treg cells). The meta-analysis of data on conventional DCs from rats and data on monocyte-derived macrophages from humans revealed 7 IFN-regulated genes that were negatively regulated in both human and rat SpA (i.e., IRF1, STAT1, CXCL9, CXCL10, IFIT3, DDX60, and EPSTI1).",
            "output": [
                "Is reverse interferon signature characteristic of antigen-presenting cells in human and rat spondyloarthritis?"
            ]
        },
        {
            "id": "task847-7af3b3f47c184cb08e0425c55242606d",
            "input": "During development of the vertebrate skeleton, chondrocytes form a cartilage template that is gradually replaced by bone. Hormones of the Hedgehog (HH) family have been implicated in the ossification process, but their exact relationship to normal or pathogenic bone formation is unclear. This study was undertaken to establish a genetic tool that allows the discrete inactivation of genes in spinal chondrocytes, and to investigate in vivo how chondrocyte-specific ablation of the inhibitory HH receptor Patched 1 (Ptch1) affects skeleton integrity.', 'A Cre-deleter mouse strain, mb1-Cre, for selective gene recombination in spinal chondrocytes was identified by in situ hybridization and histologic analysis. The mb1-Cre(+/-) animals were crossed with mice that harbor a loxP-flanked Ptch1 gene (Ptch1(flox/flox) ) to abrogate the inhibition of the HH signaling pathway in chondrocytes. The skeletal integrity of F1 mice was characterized by high-resolution flat-panel-based volume computed tomography and histologic staining procedures.', 'During the first weeks after birth, all mb1-Cre(+/-) /Ptch1(flox/flox) mice developed progressive spinal fusion with malformation of the vertebrae. This phenotype was caused by aberrant chondrocyte proliferation in the intervertebral discs that blocked endochondral ossification. Importantly, the disease pattern occurred in an inflammation-independent manner.",
            "output": [
                "Does inactivation of patched1 in murine chondrocytes cause spinal fusion without inflammation?"
            ]
        },
        {
            "id": "task847-397d2baec80d44698b7cb76ec004c1f2",
            "input": "Rumination syndrome is characterized by effortless recurrent regurgitation of recently ingested food into the mouth, with consequent expulsion or re-chewing and swallowing. We investigated whether rumination is under volitional control and can be reversed by behavioral treatment.', 'We performed a prospective study of 28 patients who fulfilled the Rome criteria for rumination and had no organic disorders on the basis of a thorough evaluation. The diagnosis of rumination was confirmed by intestinal manometry (abdominal compression associated with regurgitation). Patients were trained to modulate abdominothoracic muscle activity under visual control of electromyographic recordings. Recordings were made after challenge meals, before training (baseline), and during 3 treatment sessions. Outcome was measured by questionnaires administered daily for 10 days before training, immediately after training, and at 1,\\xa03, and 6 months after training.', 'By the end of the 3 sessions, patients had effectively learned to reduce intercostal activity (by 50% \u00b1 2%; P < .001 vs basal) and anterior wall muscle activity (by 30% \u00b1 6%; P < .001 vs basal). Patients reported 27 \u00b1 1 regurgitation episodes/day at baseline and 8 \u00b1 2 episodes/day immediately after treatment. Regurgitation episodes decreased further to 4 \u00b1 1 episodes at 6\\xa0months after training.",
            "output": [
                "Does biofeedback-guided control of abdominothoracic muscular activity reduce regurgitation episodes in patients with rumination?"
            ]
        },
        {
            "id": "task847-e7337edee46f41f8a417cb2f5e0f6416",
            "input": "Paeonol is a phenolic compound isolated mainly from Moutan cortex, root bark of Chinese Peony tree. Moutan cortex holds a significant value in traditional Chinese medicine for alleviating various oxidative stress-related diseases mainly atherosclerosis and myocardial infarction. The present study seeks to identify the protective mechanisms of paeonol in oxidative stress-induced premature senescence in endothelial cells.', 'HUVECs were pretreated with paeonol or DMSO control at different doses for 24h prior to an exposure of 200\u03bcM of reactive oxygen species (ROS) inducer, hydrogen peroxide (H2O2). The protective effects of paeonol against H2O2-induced senescence were evaluated and the activation of Sirtuin 1 pathway by paeonol pretreatment was investigated in HUVECs.', 'Paeonol attenuated H2O2-induced cell growth arrest at G0/G1 phase, reduced the percentage of SA-\u03b2-Gal positive cells and increased BrdU incorporation. In addition, enzymatic Sirt1 activation assay indicated that paeonol significantly increased lysyl deactylase activity of Sirt1 enzyme with a fold change of 2.4\u00b10.195 (p<0.05). Furthermore, pretreatment with paeonol significantly decreased the levels of p53, acetyl H3K14 and H4K16 protein expression upregulated by H2O2 stimulation. The changes in the histone protein levels were accompanied with an increase in Sirt1 protein expression level.",
            "output": [
                "Does paeonol protect against premature senescence in endothelial cells by modulating Sirtuin 1 pathway?"
            ]
        },
        {
            "id": "task847-1ec05dcd98c242c2b81ca2d7aef673e7",
            "input": "Indoleamine 2,3-dioxygenase (IDO), an enzyme that is ubiquitously distributed in mammalian tissues and cells, converts tryptophan to kynurenine, and is also known as a key molecule that promotes apoptosis in lymphocytes and neurons. In this study, we established hepatitis B virus (HBV)-transgenic (Tg)/IDO-knockout (KO) mice and examined the influence of IDO in a murine fulminant hepatitis model induced by HBV-specific cytotoxic T lymphocytes (CTL). An increase of IDO expression in the livers of HBV-Tg/IDO-wild-type (WT) mice administered HBV-specific CTL was confirmed by real-time polymerase chain reaction, western blotting, and evaluating IDO activity. Plasma alanine aminotransferase (ALT) levels in HBV-Tg/IDO-KO mice after HBV-specific CTL injection significantly decreased compared with those in HBV-Tg/IDO-WT mice. An inhibitor of IDO, 1-methyl-d-tryptophan (1-MT), could also attenuated the observed liver injury induced by this HBV-specific CTL. The expression levels of cytokine and chemokine mRNAs in the livers of HBV-Tg/IDO-WT mice were higher than those in the livers of HBV-Tg/IDO-KO mice. The administration of kynurenine aggravated the liver injury in HBV-Tg/IDO-KO mice injected with HBV-specific CTL. Simultaneous injection of recombinant murine interferon (IFN-\u03b3) and kynurenine also increased the ALT levels in HBV-Tg/IDO-KO mice. The liver injury induced by IFN-\u03b3 and kynurenine was improved in HBV-Tg/tumor necrosis factor-\u03b1-KO mice.",
            "output": [
                "Does kynurenine production mediated by indoleamine 2,3-dioxygenase aggravate liver injury in HBV-specific CTL-induced fulminant hepatitis?"
            ]
        },
        {
            "id": "task847-cb48eb7e0bf54b67a97a0c036e06061c",
            "input": "Is the activity of sirtuin 3 (SIRT3) altered in granulosa and cumulus cells from young women with reduced ovarian reserve or women of advanced maternal age?",
            "output": [
                "Are mitochondrial SIRT3 and its target glutamate dehydrogenase altered in follicular cells of women with reduced ovarian reserve or advanced maternal age?"
            ]
        },
        {
            "id": "task847-af38fbbc7688490ab0d0c0158ffbc54c",
            "input": "Despite increased identification of spotted fever group rickettsioses (SFGR) in animals and arthropods, human SFGR are poorly characterized in Taiwan.', 'Patients with suspected Q fever, scrub typhus, murine typhus, leptospirosis, and dengue fever from April 2004 to December 2009 were retrospectively investigated for SFGR antibodies (Abs). Sera were screened for Rickettsia rickettsii Abs by indirect immunofluorescence antibody assay (IFA), and those with positive results were further examined for Abs against R. rickettsii, R. typhi, R. felis, R. conorii, and R. japonica using micro-immunofluorescence (MIF) tests. Polymerase chain reaction (PCR) for detection of SFGR DNA was applied in those indicated acute infections. Case geographic distribution was made by the geographic information system software.', 'A total of 413 cases with paired serum, including 90 cases of Q fever, 47 cases of scrub typhus, 12 cases of murine typhus, 6 cases of leptospirosis, 3 cases of dengue fever, and 255 cases of unknown febrile diseases were investigated. Using IFA tests, a total of 49 cases with 47 (11.4%) and 4 (1.0%) cases had sera potentially positive for R. rickettsii IgG and IgM, respectively. In the 49 cases screened from IFA, MIF tests revealed that there were 5 cases of acute infections (3 possible R. felis and 2 undetermined SFGR) and 13 cases of past infections (3 possible R. felis and 10 undetermined SFGR). None of the 5 cases of acute infection had detectable SFGR DNA in the blood specimen by PCR. Possible acute infection of R. felis was identified in both one case of Q fever and scrub typhus. The geographic distribution of SFGR cases is similar with that of scrub typhus.",
            "output": [
                "Are human spotted fever group rickettsioses underappreciated in southern Taiwan , particularly for the species closely-related to Rickettsia felis?"
            ]
        },
        {
            "id": "task847-3d121788a7de4cf386fb7b4126c19e9b",
            "input": "Mitochondrial DNA (mtDNA) copy number correlates with tumor pathology in some cancers.', 'To investigate mtDNA copy number in head and neck cancer (HNC).', 'mtDNA copy number was determined and compared between HNC patients and malignancy-free controls.', 'The mtDNA copy number was significantly higher in HNC patients, increased with cancer progression and correlated negatively with patient survival.",
            "output": [
                "Is mitochondrial DNA copy number associated with diagnosis and prognosis of head and neck cancer?"
            ]
        },
        {
            "id": "task847-6e2c1d5d55b24529a1853fbddfa36e50",
            "input": "The checkpoint kinase 1 (Chk1) functions not only in genotoxic stresses but also in normal cell cycle progression, particularly in the initiation, progression and fidelity of unperturbed mitosis. In this study, we investigated the role of Chk1 in regulating the metaphase-anaphase transition in mammalian cells.', 'The mitotic progression was monitored by flow cytometry analysis. The levels of cyclin B1, Cdc20 and Mad2 were measured by Western blotting. Metaphase chromosome alignment and the subcellular localization of Cdc20 and Mad2 were analyzed by immunofluorescence and confocal microscopy.', 'Cyclin B1 degradation and the metaphase-anaphase transition were severely blocked by Chk1 siRNA. Depletion of Chk1 induced chromosome alignment defect in metaphase cells. The kinetochore localization of Cdc20, Mad2 was disrupted in Chk1 depleted cells. Chk1 abrogation also dramatically reduced the protein expression levels of Cdc20 and Mad2.",
            "output": [
                "Is chk1 required for the metaphase-anaphase transition via regulating the expression and localization of Cdc20 and Mad2?"
            ]
        },
        {
            "id": "task847-b5206002a61243be8b6c9c7a373e84f8",
            "input": "Sedum sarmentosum Bunge, a traditional Chinese herbal medicine, has a wide range of clinical effects, including anti-oxidation, anti-inflammation, and anti-cancer properties. In this study, we determined whether S. sarmentosum Bunge Extract (SSBE) has anti-fibrotic effects on renal tissues.', 'We investigated the effects of SSBE on aristolochic acid (AA)-induced injury to renal tubular epithelial cells (RTECs) in vitro and unilateral ureteral obstruction (UUO)-induced renal fibrosis in vivo by evaluating epithelial-to-mesenchymal transition (EMT) and the accumulation of extracellular matrix (ECM) components. Furthermore, we examined the expression levels of TGF-\u03b21 and its receptor.', 'In cultured RTECs (NRK-52E), AA promoted renal EMT and ECM accumulation by up-regulating the expression of mesenchymal markers and ECM components and by down-regulating the expression of epithelial markers. In addition, AA induced an imbalance between MMP-2 and TIMP-2 and enhanced expression of TGF-\u03b21 and its receptor. SSBE treatment significantly inhibited AA-induced TGF-\u03b21 expression and prevented the induction of EMT and deposition of ECM. In the UUO rats, tubular injury and interstitial fibrosis were obviously increased. SSBE administration protected renal function, as indicated by reduced serum creatinine levels, and alleviated renal interstitial fibrosis. These anti-fibrotic effects were associated with a reduction in TGF-\u03b21 expression and inhibition of EMT and ECM accumulation.",
            "output": [
                "Does sedum sarmentosum Bunge extract exert renal anti-fibrotic effects in vivo and in vitro?"
            ]
        },
        {
            "id": "task847-3a364d18c71144bcb9ab0b2f33969169",
            "input": "Asthma is characterized by airway inflammation and remodelling in which matrix metalloproteinases (MMPs) play an important role. MMP-9 is the major MMP found in the bronchoalveolar lavage fluids and bronchial biopsies from patients with allergic asthma after allergen challenge, where it correlates with the count of neutrophils and macrophages. However, the cellular sources of MMP-9 in this inflammatory condition have not yet been clearly identified. This work was undertaken to analyse whether neutrophils may be a source of MMP-9 in the allergic asthma condition upon allergen challenge.', 'Neutrophils from allergic asthmatic patients were in\\xa0vitro stimulated, and the levels of MMP-9 release were measured in the cell culture supernatants using enzyme-linked immunosorbent assay (ELISA) and zymography.', 'We show that MMP-9 is released by neutrophils, but not by eosinophils from allergic asthmatic patients in response to allergens to which the patients were sensitized. Neutrophils also released MMP-9 in response to anti-IgE Abs, and agonist Abs against Fc\u03b5RI, Fc\u03b5RII/CD23 and galectin-3. Inhibitors of transcription and translation, actinomycin D and cycloheximide, partially cancelled this process, suggesting that MMP-9 is also de novo synthesized in response to stimuli. We also show evidence that the MAPKs, p38 and extracellular signal-regulated kinase, as well as the transcription factor NF-\u03baB, are involved, as specific chemical inhibitors of these cell-signalling pathways abolished the anti-IgE/allergen-dependent MMP-9 release.",
            "output": [
                "Do neutrophils from allergic asthmatic patients produce and release metalloproteinase-9 upon direct exposure to allergens?"
            ]
        },
        {
            "id": "task847-dff3fb459e3d4c9fa9da00cec432a39f",
            "input": "In several reports, C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here, we investigate this link and the degree of C3 activation in elderly individuals.', 'In this study, C3 and C4 and the activation fragment C3a-desArg were analysed in 1016 subjects aged 70, in which blood pressure, lipid variables and fasting blood glucose were assessed.', 'C3 levels were related to all the investigated classical cardiovascular risk factors and the metabolic syndrome (BMI, waist circumference, fat distribution, blood pressure, blood glucose levels, TG) except total cholesterol and LDL cholesterol in a highly significant fashion (Spearman up to 0,5; P\\xa0<\\xa00\u00b70001). C4 and C3a-desArg were associated in the same fashion but less significantly, while the ratios C4/C3 or C3a-desArg/C3 were not, indicating that the association was not directly related to complement activation. The levels C3 and to a lesser degree C4 and C3a-desArg were associated particularly with CRP, but also with E-selectin and ICAM-1. In addition, C3 and C4 levels were shown to decline significantly in 15 female subjects enrolled in a weight-reduction programme over 4\\xa0months.",
            "output": [
                "Are c3 and C4 strongly related to adipose tissue variables and cardiovascular risk factors?"
            ]
        },
        {
            "id": "task847-e4aca7c06e054526aa3c3476108773f6",
            "input": "The use of a system for continuous control of endotracheal tube cuff pressure reduced the incidence of ventilator-associated pneumonia (VAP) in one randomized controlled trial (RCT) with 112 patients but not in another RCT with 142 patients. In several guidelines on the prevention of VAP, the use of a system for continuous or intermittent control of endotracheal cuff pressure is not reviewed. The objective of this study was to compare the incidence of VAP in a large sample of patients (n\\u2009=\\u2009284) treated with either continuous or intermittent control of endotracheal tube cuff pressure.', 'We performed a prospective observational study of patients undergoing mechanical ventilation during more than 48 hours in an intensive care unit (ICU) using either continuous or intermittent endotracheal tube cuff pressure control. Multivariate logistic regression analysis (MLRA) and Cox proportional hazard regression analysis were used to predict VAP. The magnitude of the effect was expressed as odds ratio (OR) or hazard ratio (HR), respectively, and 95% confidence interval (CI).', 'We found a lower incidence of VAP with the continuous (n\\u2009=\\u2009150) than with the intermittent (n\\u2009=\\u2009134) pressure control system (22.0% versus 11.2%; p\\u2009=\\u20090.02). MLRA showed that the continuous pressure control system (OR\\u2009=\\u20090.45; 95% CI\\u2009=\\u20090.22-0.89; p\\u2009=\\u20090.02) and the use of an endotracheal tube incorporating a lumen for subglottic secretion drainage (SSD) (OR\\u2009=\\u20090.39; 95% CI\\u2009=\\u20090.19-0.84; p\\u2009=\\u20090.02) were protective factors against VAP. Cox regression analysis showed that the continuous pressure control system (HR\\u2009=\\u20090.45; 95% CI\\u2009=\\u20090.24-0.84; p\\u2009=\\u20090.01) and the use of an endotracheal tube incorporating a lumen for SSD (HR\\u2009=\\u20090.29; 95% CI\\u2009=\\u20090.15-0.56; p\\u2009<\\u20090.001) were protective factors against VAP. However, the interaction between type of endotracheal cuff pressure control system (continuous or intermittent) and endotracheal tube (with or without SSD) was not statistically significant in MLRA (OR\\u2009=\\u20090.41; 95% CI\\u2009=\\u20090.07-2.37; p\\u2009=\\u20090.32) or in Cox analysis (HR\\u2009=\\u20090.35; 95% CI\\u2009=\\u20090.06-1.84; p\\u2009=\\u20090.21).",
            "output": [
                "Does continuous endotracheal tube cuff pressure control system protect against ventilator-associated pneumonia?"
            ]
        },
        {
            "id": "task847-29cc338845234172ada57de647daba80",
            "input": "Within Australian hospitals, cardiac and respiratory arrests result in a resuscitation attempt unless the patient is documented as not for resuscitation.', 'To examine the consistency of policies and documentation for withholding in-hospital resuscitation across health services.', 'An observational, qualitative review of hospital policy and documentation was conducted in June 2013 in three public and two private sector hospitals in metropolitan Melbourne. Not for resuscitation (NFR) forms were evaluated for physical characteristics, content, authorisation and decision-making. Hospital policies were coded for alerts, definition of futility and burden of treatment and management of discussions and dissent.', 'There was a lack of standardisation, with each site using its own unique NFR form and accompanying site-specific policies. Differences were found in who could authorise the decision, what was included on the form, the role of patients and families, and how discussions were managed and dissent resolved. Futility and burden of treatment were not defined independently. These inconsistencies across sites contribute to a lack of clarity regarding the decision to withhold resuscitation, and have implications for staff employed across multiple hospitals.",
            "output": [
                "Does comparison of not for resuscitation ( NFR ) form across five Victorian health services?"
            ]
        },
        {
            "id": "task847-6ce6fff2095848c2957fdee5a31ae3d4",
            "input": "Lymphocyte infiltration is a common feature of radiation-induced pneumonitis and fibrosis, but their contribution to the pathogenic processes is still unclear. Here, we addressed the impact of thorax irradiation on the T cell compartment with a focus on immunosuppressive regulatory T cells (Treg).', 'C57BL/6 wild type mice (WT) received anesthesia only (sham controls, 0 Gy) or were exposed to a single dose of whole thorax irradiation (15 Gy). Immune cells from lung tissue, spleen, and cervical lymph nodes were collected 10 to 84 days post-irradiation and phenotypically characterized by flow cytometry.', 'Whole thorax irradiation provoked an increased influx of CD3+ T cells at 42 and 84 days post-irradiation. In contrast, local irradiation caused a sustained reduction in CD3+ T cells in peripheral lymphoid tissues. Interestingly, we observed a significant local and systemic increase in the fraction of CD4+ T cells expressing the transcription factor forkhead box P3 (FoxP3), the phenotypic marker for murine Treg, at day 21 post-irradiation. The accumulation of Treg was associated with increased levels of T cells expressing surface proteins characteristic for recruitment and immunosuppressive activity, e.g. CD103, CTLA-4 and CD73. Importantly, Treg isolated at this time point were able to suppress CD4+ effector T cells to a similar extent as Treg isolated from control mice.",
            "output": [
                "Does thorax irradiation trigger a local and systemic accumulation of immunosuppressive CD4+ FoxP3+ regulatory T cells?"
            ]
        },
        {
            "id": "task847-ffcf6227365b43269e63fbd94a03b565",
            "input": "To examine the effect of TRIB3 on endoplasmic reticulum stress induced \u03b2-cell apoptosis and to investigate the mechanism with a specific emphasis on the role of NF-\u03baB pathway.', 'We investigated the effect of TRIB3 on ER stress-induced \u03b2-cell apoptosis in INS-1 cells and primary rodent islets. The potential role of TRIB3 in ER stress inducer thapsigargin (Tg)-induced \u03b2-cell apoptosis was assessed using overexpression and siRNA knockdown approaches. Inducible TRIB3 \u03b2-cells, regulated by the tet-on system, were used for sub-renal capsule transplantation in streptozotocin (STZ)-diabetic mice, to study the effect of TRIB3 on ER stress-induced \u03b2-cell apoptosis in vivo. Apoptosis was determined by TUNEL staining both in vivo and in vitro, while the molecular mechanisms of NF-\u03baB activation were investigated.', 'TRIB3 was induced in ER-stressed INS-1 cells and rodent islets, and its overexpression was accompanied by increased \u03b2-cell apoptosis. Specifically, TRIB3 overexpression enhanced Tg-induced INS-1 derived \u03b2-cell apoptosis both in vitro and in sub-renal capsular transplantation animal model. Additionally, knockdown of Trib3 blocked Tg-induced apoptosis. Mechanistically, the induction of TRIB3 during ER stress resulted in the activation of NF-\u03baB and aggravated INS-1 derived \u03b2-cell apoptosis, while inhibiting the NF-\u03baB pathway significantly abrogated this response and prevented \u03b2-cell apoptosis, both in vitro and in sub-renal capsular transplantation animal model.",
            "output": [
                "Does tRIB3 alter endoplasmic reticulum stress-induced \u03b2-cell apoptosis via the NF-\u03baB pathway?"
            ]
        },
        {
            "id": "task847-fd7a92365257444684489fcab68a66e5",
            "input": "Surgical site infections (SSI) are associated with increased costs and length of hospital stay, readmission rates, and mortality. The aim of this study was to identify risk factors for SSI in patients undergoing laparoscopic cholecystectomy.', \"Analysis of 35,432 laparoscopic cholecystectomies of a prospective multicenter database was performed. Risk factors for SSI were identified among demographic data, preoperative patients' history, and operative data using multivariate analysis.\", 'SSIs after laparoscopic cholecystectomy were seen in 0.8\\xa0% (n\\u2009=\\u2009291) of the patients. Multivariate analysis identified the following parameters as risk factors for SSI: additional surgical procedure (odds ratio [OR] 4.0, 95\\xa0% confidence interval [CI] 2.2-7.5), age over 55\\xa0years (OR 2.4 [1.8-3.2]), conversion to open procedure (OR 2.6 [1.9-3.6]), postoperative hematoma (OR 1.9 [1.2-3.1]), duration of operation >60\\xa0min (OR 2.5 [1.7-3.6], cystic stump insufficiency (OR 12.5 [4.2-37.2]), gallbladder perforation (OR 6.2 [2.4-16.1]), gallbladder empyema (OR 1.7 [1.1-2.7]), and surgical revision (OR 15.7 [10.4-23.7]. SSIs were associated with a significantly prolonged hospital stay (p\\u2009<\\u20090.001), higher postoperative mortality (p\\u2009<\\u20090.001), and increased rate of surgical revision (p\\u2009<\\u20090.001).",
            "output": [
                "Is additional surgical procedure a risk factor for surgical site infections after laparoscopic cholecystectomy?"
            ]
        },
        {
            "id": "task847-aa9963e8097a46f5a3148e75314f3d04",
            "input": "Cannulation of the common bile duct (CBD) is the initial and sometime challenging step in endoscopic retrograde cholangiopancreatography (ERCP) procedure. Endoscopists often use cannulation attempts and cannulation time to grade cannulation difficulty, but a standard system has yet to be established. The objective of this study was to compare cannulation times with numbers of cannulation attempts, as measures of cannulation difficulty.', 'We conducted a prospective study in a tertiary referral center, enrolling 58 patients who were undergoing ERCP for a variety of indications. Cannulation time and the number of cannulation attempts were recorded for each patient. A subset of 14 ERCPs had two observers assessing attempts at cannulation. Cannulation time, number of attempts and inter-observer variability in assessment of attempts were compared and studied.', 'The degree of agreement between two the methods (cannulation times and number of cannulation attempts) was unacceptable. There were considerable discrepancies between attempt tallies from two observers but the mean difference was statistically insignificant.",
            "output": [
                "Is cannulation time a more accurate measure of cannulation difficulty in endoscopic retrograde cholangiopancreatography than the number of attempts?"
            ]
        },
        {
            "id": "task847-2b62fb6858534b259eff3a11e93ca4bf",
            "input": "Neuroblastoma is a common pediatric solid tumor with poor outcome for metastatic disease. Thus, novel therapeutic options are of main interest. The anti-neoplastic properties of taurolidine have been demonstrated on a variety of human cancer cells. However, data on neuroblastoma is lacking. Therefore, our aim was to evaluate the effect of taurolidine on growth of neuroblastoma cell lines.', 'Neuroblastoma SK-N-BE(2)-M17 and SK-N-SH cells and nonmalignant human umbilical vein endothelial cells as controls were incubated with increasing concentrations of taurolidine (100, 250, 500 \u00b5M). Cell growth was examined after 12, 24, and 48 hours of exposure.', 'Inhibition of cell growth by taurolidine was seen in both malignant cell lines. When compared with human umbilical vein endothelial cells, the neuroblastoma cell lines were significantly more responsive to taurolidine.",
            "output": [
                "Does taurolidine specifically inhibit growth of neuroblastoma cell lines in vitro?"
            ]
        },
        {
            "id": "task847-ffe23796354142dbaa4fd7ac7717760e",
            "input": "Removal of a humeral component during revision shoulder arthroplasty can be difficult. If the component cannot be extracted from above, an alternative approach may compromise bone integrity. Two potential solutions are a humeral window and a longitudinal split. This review was performed to determine complications and outcomes associated with these osteotomies during revision arthroplasty.', 'We reviewed records of 427 patients undergoing revision shoulder arthroplasty, identifying those requiring a window or longitudinal split. Outcomes were intraoperative and postoperative complications, rate of healing, and security of implant fixation.', 'Twenty-six patients underwent creation of a window. Six intraoperative fractures were documented: 5 in greater tuberosity and 1 in humeral shaft. At radiographic follow-up, 23 of 26 windows healed; 2 patients had limited follow-up, and 1 did not have follow-up at our institution. Nineteen patients underwent longitudinal osteotomy. One had intraoperative fracture in greater tuberosity. At radiographic follow-up, 17 of 19 longitudinal splits healed; 1 had limited radiographic follow-up, and 1 did not have follow-up at our institution. Three patients underwent formation of both window and longitudinal osteotomy. At radiographic follow-up, all shoulders healed, and there were no intraoperative or postoperative fractures or malunions.",
            "output": [
                "Does humeral windows and longitudinal split for component removal in revision shoulder arthroplasty?"
            ]
        },
        {
            "id": "task847-b5709cbefa4c4d24a3151f272e2c5b54",
            "input": "To investigate whether previously reported 9p21.3 single nucleotide polymorphisms (SNPs) are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying arterial aneurysms. Common variants in the 9p21.3 locus have been reported to be associated with multiple cardiovascular phenotypes, including coronary artery disease and intracranial aneurysms (rs10757278 and rs1333040).', 'We used data from 338 BAVM cases participating in the University of California, San Francisco (UCSF)-Kaiser Brain AVM Study Project and 504 healthy controls to evaluate genotypes for seven common SNPs (minor allele frequency>0.05) that were imputed using 1000 Genomes Phase 1 European data (R(2)>0.87). Association with BAVM was tested using logistic regression adjusting for age, sex and the top three principal components of ancestry. Subgroup analysis included 205 BAVM cases with aneurysm data: 74 BAVM with aneurysm versus 504 controls and 131 BAVM without aneurysm versus 504 controls.', 'We observed suggestive association with BAVM and rs10757278-G (OR=1.23, 95% CI 0.99 to 1.53, p=0.064) and rs1333040-T (OR=1.27, 95% CI 1.01 to 1.58, p=0.04). For rs10757278-G, the association was stronger in BAVM cases with aneurysm (OR=1.52, 95% CI 1.03 to 2.22, p=0.032) than in BAVM without aneurysm (OR=0.98, 95% CI 0.72 to 1.34, p=0.91). Similar patterns of effects were observed for rs1333040 and for other SNPs in linkage disequilibrium (r(2)>0.8) with rs10757278.",
            "output": [
                "Do common variants on 9p21.3 are associated with brain arteriovenous malformations with accompanying arterial aneurysms?"
            ]
        },
        {
            "id": "task847-46bf853713f74491b49df54858d92c24",
            "input": "Pulp necrosis in immature teeth and the resulting periodontal apical inflammation negatively affect root formation. Resolvin E1 (RvE1) is a lipid-derived endogenous pro-resolution molecule that controls inflammation. The aim of this investigation was to evaluate the impact of RvE1 applied as an intracanal medication on root formation in nonvital immature teeth.', 'To arrest root development, pulpectomy was performed in the lower first molars of 4-week-old Wistar rats. After 3 weeks, irrigation with 2.5% sodium hypochlorite and 0.9% sterile saline was performed, and either a triple antibiotic paste (TAP) or RvE1 in saline was applied into the root canals. In the control group, access openings drilled into molars were left exposed to the oral environment. Root development and periapical repair were evaluated radiographically and histologically at 3 and 6 weeks after treatment.', 'RvE1 reduced periapical lesion size compared with the control at 3 weeks, which was similar to TAP. Inflammatory response in the RvE1-treated group was markedly reduced compared with both TAP and control specimens. At 6 weeks, root development was observed in both groups, but RvE1 treatment produced less cellularity with more regular calcified tissue deposition.",
            "output": [
                "Does intracanal delivery of Resolvin E1 control inflammation in necrotic immature rat teeth?"
            ]
        },
        {
            "id": "task847-5e2d7cd4427840da87366aac3dd864de",
            "input": "CENTRAL, Medline, Embase, Web of Science, LILACS and BBO databases, the Brazilian database of thesis and dissertations (Banco de Teses CAPES), a Brazilian register of ethically approved projects involving human beings (SISNEP) and two registers of ongoing trials (Current Controlled Trials and Clinical-Trials.gov). Reference lists were also scanned for relevant papers. Study authors were contacted for additional information.', 'Individual or cluster-randomised or quasi-randomised controlled trials conducted in children under seven were included.', 'Study selection and data abstraction were conducted by two reviewers independently. Risk of bias assessment was undertaken using the Cochrane Collaboration tool. Meta-analyses of prevented fractions (PF) were performed to assess the effect of fluoride toothpaste on the dmft and dmfs. Meta-analyses were also performed to obtain a pooled relative risk (RR) to assess the effect of fluoride toothpastes on the proportion of children developing caries.', 'Eight studies were included. When standard F toothpastes were compared to placebo or no intervention, significant caries reduction at surface (PF = 31%; 95% CI 18-43; 2644 participants in five studies), tooth (PF = 16%; 95% CI 8-25; 2555 participants in one study) and individual (RR = 0.86; 95% CI 0.81-0.93; 2806 participants in two studies) level were observed. Low F toothpastes were effective only at surface level (PF = 40%; 95% CI 5-75; 561 participants in two studies).",
            "output": [
                "Does limited evidence suggest standard fluoride toothpaste reduces caries potential in preschool children?"
            ]
        },
        {
            "id": "task847-7cb7d14193424c998d3d9a44342369c2",
            "input": "Peroxisome proliferator-activated receptor (PPAR)-\u03b2/\u03b4 is a transcription factor that belongs to the nuclear hormone receptor family. There is little information about the effects of the immediate administration of specific ligands of PPAR-\u03b2/\u03b4 (GW0742) in animal models of acute ischemic stroke. Using a rat model of middle cerebral ischemia occlusion (MCAO) in\\xa0vivo, we have investigated the effect of pretreatment with GW0742 before MCAO.', 'The neuroprotective effect of GW0742 against acute ischemic stroke was evaluated by the neurologic deficit score (NDS), dry-wet weight, and 2,3,5-triphenyltetrazolium chloride staining. The levels of interleukin (IL)-1\u03b2, nuclear factor (NF)-\u03baB, and tumor necrosis factor (TNF)-\u03b1 were detected by an enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), Bax, and Bcl-2 were detected by Western blot. The apoptotic cells were counted by in situ terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay.', 'The pretreatment with GW0742 significantly increased the expression of Bcl-2, and significantly decreased in the volume of infarction, NDS, edema, expressions of IL-1\u03b2, NF-\u03baB, TNF\u03b1, and Bax, contents of iNOS and the apoptotic cells in infarct cerebral hemisphere compared with rats in the vehicle group at 24\\xa0hours after MCAO.",
            "output": [
                "Does activation of peroxisome proliferator-activated receptor \u03b2/\u03b4 attenuate acute ischemic stroke on middle cerebral ischemia occlusion in rats?"
            ]
        },
        {
            "id": "task847-96b2d1cfb5b14349b6d962ba35d933b8",
            "input": "Accumulating evidence has indicated that inflammation may act as a potential mechanism underlying post-operative cognitive dysfunction (POCD). High-mobility group box 1 (HMGB1), as a known late mediator of inflammation, is involved in the development of post-operative complications. Thus, we sought to determine the role of HMGB1 in reflecting POCD following major gastrointestinal surgery.', 'Fifty-three elderly patients undergoing gastrointestinal surgery were recruited, and 50 patients completed the study. Serum HMGB1 and interleukin (IL)-6 levels were measured pre-operatively and at 6 h, day 1 and day 3 post-operatively. Neuropsychological tests were administered before and 1 week after surgery. POCD was determined using a Z score \u2265 1.96.', 'Seventeen (34%, 17/50) patients developed POCD at 1 week. The POCD group had higher serum HMGB1 levels at day 1 (12.15 \u00b1 3.12 vs. 9.91 \u00b1 3.15 ng/ml, P = 0.021) and day 3 (11.04 \u00b1 2.88 vs. 8.52 \u00b1 3.31 ng/ml, P = 0.011). IL-6 levels at 6 h (51.18 \u00b1 15.22 vs. 39.20 \u00b1 14.32 pg/ml, P = 0.009) and day 1 (41.59 \u00b1 11.08 vs. 33.81 \u00b1 11.42 pg/ml, P = 0.026) were significantly higher in POCD patients. Serum values of IL-6 at 6 h, HMGB1 at day 1 and levels of education showed positive correlations with Z scores. HMGB1 at day 3 and IL-6 at 6 h were independent risk factors.",
            "output": [
                "Does serum high-mobility group box 1 protein correlate with cognitive decline after gastrointestinal surgery?"
            ]
        },
        {
            "id": "task847-234a916219e9427e994bd38c5ec702ec",
            "input": "The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE).', 'Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV(+)). Presence of bacterial infection (defined as \u226510(4) colony-forming units/mL) was compared between BAL HAdV(+) and HAdV negative (HAdV(-)) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup.', 'Species C HAdVs were identified in 23 of 24 (96%) HAdV(+) children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV(+) BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38-7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV(+). Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027).",
            "output": [
                "Is adenovirus species C associated with chronic suppurative lung diseases in children?"
            ]
        },
        {
            "id": "task847-d169ffee948b478691777369e8371c8c",
            "input": "It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of preexisting white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of preexisting leukoaraiosis of presumed ischemic origin is independently associated with outcome after TBI.', 'We retrospectively analyzed consecutive, prospectively enrolled patients of \u226550\\xa0years (n\\xa0=\\xa0136) who were admitted to a single neurological/trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range 0-4) reflecting increasing severity of leukoaraiosis. Outcome was ascertained according to the modified Rankin Scale (mRS) and Glasgow outcome scale (GOS) at 3 and 12\\xa0months, respectively.', 'After adjustment for other factors, leukoaraiosis severity was significantly associated with a poor outcome at 3 and 12\\xa0months defined as mRS 3-6 and GOS 1-3, respectively. The independent association between leukoaraiosis and poor outcome remained when the analysis was restricted to patients who survived up to 3\\xa0months, had moderate-to-severe TBI [enrollment Glasgow Coma Scale (GCS) \u226412; p\\xa0=\\xa00.001], or had mild TBI (GCS 13-15; p\\xa0=\\xa00.002), respectively.",
            "output": [
                "Does severe leukoaraiosis portend a poor outcome after traumatic brain injury?"
            ]
        },
        {
            "id": "task847-8bbbf3a485bd480980f46b6ad985dd11",
            "input": "To investigate the factors related to communications in home medical care settings, and the association between such factors and a patient's place of death.\", 'A questionnaire survey of 295 families of patients who had previously received home medical care was carried out in June and July 2011. The response rate was 83.8% (n\\u2009=\\u2009227). Following the exclusion of families where the patient was still alive, or where the place of death was unknown, 143 questionnaires were available for analysis. Logistic regression was used to identify significant associations between possible factors related to communication and occurrence of home death.', \"Home death was observed in 66.4% (n\\u2009=\\u200995) of the families analyzed. Home death was significantly associated with the frequency of doctor home-visits per week (OR 2.835, 95% CI 1.436-5.597, P\\u2009=\\u20090.003). There was no statistically significant association between home death and any of the other variables included: malignant tumors as primary disease, independence in daily activity, duration of home medical care, duration of doctor's visits, experience of doctor-patient communication without family, doctor-family communication without the patient or explanation from the doctor on the phone, existence of home-visit nursing services, existence of family's anxieties and/or questions, age of primary caregiver(s) and sex of primary caregiver(s).",
            "output": [
                "Is home death associated with frequency of physician home medical care visits : a questionnaire survey on communications in home medical care settings?"
            ]
        },
        {
            "id": "task847-bbcd6e7d17bd4eb3a3114bd315282835",
            "input": "Edema due to capillary leak is a generalized and life threatening event in sepsis and major burns for which there is no causal treatment. Local burn wounds are an ideal model to investigate the impact of a new therapeutic agent on edema formation. We aimed to identify peptide sequences of cingulin that can attenuate stress-induced endothelial cytoskeleton disarrangement in vitro and which reduce burn-induced edema in vivo.', 'Cingulin-derived peptides were screened in high content cell culture assays monitoring actin displacement and endothelial cell/cell contacts. The ears of male hairless mice (n=44) were inflicted with full thickness burns using a hot air jet. Mice with and without burn injuries were treated with Xib13 or solvent by continuous intraperitoneal application for 3 days. Edema, microcirculation, leukocyte-endothelial interactions and angiogenesis - measured as non-perfused area - were investigated over a 12-day period using intravital fluorescence microscopy.', 'Xib13 reduced endothelial stress formation and stabilized endothelial tight junctions in cell-cultures. In the burn model, Xib13 improved angiogenesis compared to controls (non-perfused area on day 12: 5.7\u00b11.5% vs. 12.0\u00b12.1%; p<0.05). Edema was significantly reduced at all observation points in Xib13-treated animals as compared to controls (day 12: 67.6\u00b12.6% vs. 83.2\u00b16.4%).",
            "output": [
                "Does peptide XIB13 reduce capillary leak in a rodent burn model?"
            ]
        },
        {
            "id": "task847-3caec066cfa444699e7ee4d65421328f",
            "input": "The long noncoding RNA HOTAIR has been reported to be a good biomarker for poor prognosis in a variety of human cancers. However, whether HOTAIR could serve as novel biomarker to predict prognosis in cervical cancer or not is unknown. The aim of the present study was to examine the expression of HOTAIR in cervical cancers and to investigate the relationship between this lncRNA expression levels and existing clinicopathological factors and patient survival.', 'We examined the expression of HOTAIR in 218 cervical cancer tissues and matched 218 adjacent normal tissues using quantitative real-time RT-PCR and analyzed its correlation with the clinical parameters.', 'The results showed that HOTAIR expression in cervical cancer tissues was significantly upregulated compared with the matched nontumorous tissues (P < 0.0001). Increased HOTAIR expression was significantly correlated with FIGO stage (P < 0.0001), lymph node metastasis (P < 0.0001), depth of cervical invasion (P < 0.0001), tumor size (P = 0.006) and age (P = 0.020), but not other clinical characteristics. Moreover, cervical cancer patients with HOTAIR higher expression have shown significantly poorer overall survival (P < 0.0001) and disease-free survival (P < 0.0001) than those with lower HOTAIR expression. Univariate (P < 0.0001, HR = 4.566, 95 % CI 2.122-9.825) and multivariate (P = 0.012, HR = 2.863, 95 % CI 1.263-76.490). Cox regression analyses showed that HOTAIR expression served as an independent predictor for overall survival.",
            "output": [
                "Does overexpression of long noncoding RNA HOTAIR predict a poor prognosis in patients with cervical cancer?"
            ]
        },
        {
            "id": "task847-431ebd26d35e4f00b564ce206a141a3b",
            "input": "Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients.', '1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis.', 'The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR\\u2009=\\u20092.02, 95% CI\\u2009=\\u20091.10-3.72, p\\u2009=\\u20090.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR\\u2009=\\u20091.09, 95% CI\\u2009=\\u20090.67-1.76, p\\u2009=\\u20090.73) and scores of coronary lesions were not different among rs3798220 genotypes.",
            "output": [
                "Is lPA rs10455872 polymorphism associated with coronary lesions in Brazilian patients submitted to coronary angiography?"
            ]
        },
        {
            "id": "task847-a8409726e6a54032a8777ad469b6a24a",
            "input": "Acute kidney injury (AKI) is common after liver transplantation (OLT) and is associated with high morbidity and mortality. Previous studies have shown that interleukin-18 (IL-18) levels are associated with AKI. The purpose of this study was to determine whether plasma IL-18 levels were early predictors for AKI after liver transplantation.', 'Plasma samples were obtained from 26 patients who underwent OLT at induction of anesthesia (T1), 1 hour after the surgical incision (T2), the time of reperfusion (T3), as well as 1 (T4), 2 (T5), and 4 hours (T6) after reperfusion. Samples were also obtained at 24 hours after surgery (T7). The AKI criteria were taken according to the Acute Kidney Injury Network criteria.', 'Twelve patients (46%) developed AKI after OLT. The area under the receiver operating curve of plasma IL-18 concentrations (T4/T1) to predict AKI occurrence was 0.842 at T5, 0.905 at T6, 0.726 at T7, and 0.726 at T5 to T7.",
            "output": [
                "Is the ratio of plasma interleukin-18 a sensitive biomarker for acute kidney injury after liver transplantation?"
            ]
        },
        {
            "id": "task847-bf64d2a8d766437082321b3d043f1e50",
            "input": "CXC motif chemokine 10 (CXCL10), known as interferon-\u03b3-induced protein 10, is an inflammatory cytokine secreted by various cells in response to interferon-\u03b3. CXCR3, the receptor of CXCL10, is predominantly expressed on activated T, B, natural killer, and dendritic cells, as well as macrophages. CXCR3 promotes chemotaxis upon binding CXCL10. Serum CXCL10 levels have recently attracted attention as a post-transplantation biomarker for graft rejection. However, the correlation between the degree of T cell response to allostimulation and CXCL10 levels remains unclear. In this study, we investigated the serum and bile CXCL10 levels of patients who underwent living donor liver transplantation (LDLT) and compared them with the T cell responses to allostimulation.', 'Between February 2009 and August 2012, 41 patients underwent LDLT at Hiroshima University Hospital. Serum and bile CXCL10 levels were measured weekly for 4 weeks after surgery, while the T cell responses to allostimulation were evaluated using a mixed lymphocyte reaction with an intracellular carboxyfluorescein diacetate succinimidyl ester-labeling technique that we regularly use to monitor the\\xa0immune response to anti-donor and anti-third-party stimulation after liver transplantation. The stimulation index (SI) and CD25 expression of the CD4+ and CD8+ T cell subsets in response to allostimulation were then analyzed using flow cytometry.', 'Serum CXCL10 levels were significantly correlated with the SI values for CD8+ T cells in response to both types of allostimulation. Bile CXCL10 levels were significantly correlated with CD25 expression of CD8+ T cell subsets, especially in response to anti-donor stimulation. Patients with higher bile CXCL10 levels suffered from severe acute cellular rejection that was refractory to steroid pulse.",
            "output": [
                "Do bile CXC motif chemokine 10 levels correlate with anti-donor cytotoxic T cell responses after liver transplantation?"
            ]
        },
        {
            "id": "task847-24750da80c6a4b6eb28bf1907c100878",
            "input": "Late renal dysfunction (LRD) after liver transplantation develops due to several factors such as viral hepatitis, calcineurin inhibitor, diabetes mellitus, and hypertension. The aim of our study was to clarify the risk factors for LRD after living donor liver plantation (LDLT) by using simple criteria for LRD and paying special attention to the significance of renal biopsy.', 'Among the 98 recipients undergoing LDLT between March 2002 and June 2008, there were 77 patients who survived more than 1 year and had been followed at our clinic. LRD was simply defined as a postoperative serum creatinine level of 1.5/L or more at any point in time after 1 year from undergoing LDLT. The perioperative risk factors for developing LRD after LDLT were analyzed by uni- and multivariate analyses, and regardless of serum creatinine level, a renal biopsy was indicated when the patient developed clinical symptoms.', \"Comparing the risk factors between 22 patients with LRD and 55 without LRD, univariate analysis revealed recipient's age, generation, hypertension, hepatitis C virus (HCV) antibody-positive, pretransplantation serum creatinine level, and graft-to-recipient weight ratio to be significant risk factors. By multivariate analysis, HCV and hypertension were selected as independent risk factors. Renal biopsy was indicated in the 4 patients with proteinuria, all of whom were positive for HCV. However, by histologic and/or electron micrographic analyses, only 1 patient was diagnosed with HCV-related membranous proliferative nephritis, 1 with diabetic nephropathy, and 2 with drug (tacrolimus)\\xa0-induced renal dysfunction.",
            "output": [
                "Are hypertension and hepatitis C virus infection strong risk factors for developing late renal dysfunction after living donor liver transplantation : significance of renal biopsy?"
            ]
        },
        {
            "id": "task847-80bb6737e8d84e319b28cdae7d99ca6c",
            "input": "Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two blistering skin diseases mediated by antibodies to desmoglein 3 (Dsg3) and/or Dsg1. Phenotypic transition from PV to PF is rarely reported.', 'To determine the immune response to extracellular (EC) domains of Dsgs during this transition.', 'We report two PV patients who subsequently developed a PF phenotype. To map the conformational epitopes in these cases, we examined the reactivity of the sera of two patients by immunoprecipitation-immunoblotting analysis, using five Dsg1/Dsg3 domain-swapped molecules on a backbone of Dsg2.', 'Reactivity exclusively with the EC1 domain of Dsg1 was maintained in both PV and PF stages. No reactivity to Dsg3 in the PF stage was found in patient 1. Various changes in immunoreactivity to Dsg3 were found and the EC1 and EC2 domains of Dsg3 reacted weakly to serum taken at remission and PF stages in patient 2.",
            "output": [
                "Are antibodies to the amino-terminal domain of desmoglein 1 retained during transition from pemphigus vulgaris to pemphigus foliaceus?"
            ]
        },
        {
            "id": "task847-dd458827d2614146a68fc0efbe164ee6",
            "input": "Aiming to identify macrolide and beta-lactam resistance in clinical bacterial isolates rapidly and accurately, a two-step algorithm was developed based on detection of eight antibiotic resistance genes.', 'Targeting at genes linked to bacterial macrolide (msrA, ermA, ermB, and ermC) and beta-lactam (blaTEM, blaSHV, blaCTX-M-1, blaCTX-M-9) antibiotic resistances, this method includes a multiplex real-time PCR, a melting temperature profile analysis as well as a liquid bead microarray assay. Liquid bead microarray assay is applied only when indistinguishable Tm profile is observed.', 'The clinical validity of this method was assessed on clinical bacterial isolates. Among the total 580 isolates that were determined by our diagnostic method, 75% of them were identified by the multiplex real-time PCR with melting temperature analysis alone, while the remaining 25% required both multiplex real-time PCR with melting temperature analysis and liquid bead microarray assay for identification. Compared with the traditional phenotypic antibiotic susceptibility test, an overall agreement of 81.2% (kappa=0.614, 95% CI=0.550-0.679) was observed, with a sensitivity and specificity of 87.7% and 73% respectively. Besides, the average test turnaround time is 3.9h, which is much shorter in comparison with more than 24h for the traditional phenotypic tests.",
            "output": [
                "Does a rapid two-step algorithm detect and identifies clinical macrolide and beta-lactam antibiotic resistance in clinical bacterial isolates?"
            ]
        },
        {
            "id": "task847-fdd57bbe6fb74f74a3fcd095d97f49dd",
            "input": "There is a debate about the influence of executive functioning impairment in the functionality of Bipolar Disorder Type I, even when euthymic (EutBDI). The aim of this study was to explore this relationship, taking functional outcome from a multidimensional point of view.', 'An extended neuropsychological battery of executive tests and measures of social functioning were administered to 31 EutBDI and 25 non-psychiatric patients. Percentage of patients scoring lower than -1.64 SD was calculated for each executive measure. This was compared in terms of clinical features to those with normal performance. Partial correlations and ANCOVA were applied between psychosocial and executive variables within the EutBDI-group.', 'Patients reached poorer scores in mental flexibility, plan implementing, set-shifting, and fluency (p<0.05). 76% of patients performed poorly on some of the executive tests, although only around 1/3 reached a clinical deficit (<-1.64SD). Executive functioning was related to some clinical, evolution, and treatment variables. A better use of leisure time, higher competence for independent living and holding a skilled type of profession were significantly associated with a better performance on planning, set-shifting, and fluency tasks.",
            "output": [
                "Does cognitive executive performance influence functional outcome in euthymic type I bipolar disorder outpatients?"
            ]
        },
        {
            "id": "task847-03233a3e95ca4135a4f4db9ad3874ff4",
            "input": "Progenitor cells isolated from cardiac explant-derived cells improve cardiac function after myocardial infarction (MI). To fully realize the therapeutic potential of these cells, it is essential to develop a safe and efficient delivery method. Therefore, the objective of this study was to determine the efficacy of our newly developed approach to retrograde coronary vein (RCV) infusion of cardiac c-Kit(+) cells in a small-animal model of congestive heart failure (CHF).', 'Sprague-Dawley rats underwent experimental MI. After 21 days, cardiac explant-derived c-Kit(+) cells were delivered to both sham and CHF animals using RCV delivery. Vehicle-treated (serum-free medium) sham and CHF animals were used as controls. Cardiac function and heart tissues were evaluated 21 days post-transplantation.', 'RCV-delivered cells were retained in infarcted hearts for at least 21 days after transplantation. At 21 days post-RCV infusion, the majority of transplanted c-Kit(+)/GFP(+) cells were localized in the left ventricle. Compared with vehicle-treated CHF animals, RCV-treated rats showed a significant improvement in cardiac function. Furthermore, RCV-treated rats exhibited an increase in capillary density, a decrease in total heart collagen, and a reduction in both infarct size and cardiomyocyte hypertrophy when compared with vehicle-treated CHF rats.",
            "output": [
                "Does retrograde coronary vein infusion of cardiac explant-derived c-Kit+ cells improves function in ischemic heart failure?"
            ]
        },
        {
            "id": "task847-1d7a25ab482243aea95f7e7b908b49ca",
            "input": "Genome-wide association studies have identified single-nucleotide polymorphisms at the 10q11 locus as risk factors for myocardial infarction (MI). This locus lies upstream (\u223c80\\u200akb) of the stromal cell-derived factor-1 (SDF1) gene that codify for a chemokine with protective atherogenetic effects and with a major role in the mobilization, homing, and differentiation of endothelial progenitor cells (EPCs). The purpose of this study was to investigate the possible association of SDF1-3'A polymorphism, that upregulates SDF1 protein expression, with MI and early endothelial dysfunction and atherosclerosis in young healthy subjects.\", \"200 patients (181 men age 57.3\\u200a\u00b1\\u200a7.7 years) and 230 healthy controls (96 men, age 52\\u200a\u00b1\\u200a11.9 years) were recruited to investigate the association between MI and SDF1-3'A polymorphism. The relationship between SDF1-3'A polymorphism and brachial artery flow-mediated dilation and the number of circulating EPCs was examined in 50 healthy young adults.\", \"A significant difference in SDF1-3'A genotype distribution was observed between patients and controls (P\\u200a=\\u200a0.006). Patients carrying the A allele had a significantly reduced MI risk compared with subjects with GG genotype (odds ratio\\u200a=\\u200a0.5, 95% CI\\u200a=\\u200a0.3-0.9, P\\u200a=\\u200a0.001). SDF1-3'A polymorphism presented a significant interaction with other cardiovascular risk factors (Pinteraction\\u200a<\\u200a0. 0001). Controls carrying the A allele showed significantly higher flow-mediated dilation (13.9\\u200a\u00b1\\u200a4.9 vs 10.8\\u200a\u00b1\\u200a4.3, P\\u200a=\\u200a0.03) and significantly higher values of EPCs (0.029\\u200a\u00b1\\u200a0.009 vs 0.022\\u200a\u00b1\\u200a0.008, P\\u200a=\\u200a0.02) compared with GG homozygotes.",
            "output": [
                "Is stromal cell-derived factor-1-3 ' A polymorphism associated with decreased risk of myocardial infarction and early endothelial disturbance?"
            ]
        },
        {
            "id": "task847-06ab7e9476e748c9bb232ea00c4bbce5",
            "input": "Growing evidence documents elevated behavioral risk among sexual-minorities, including gay, lesbian, and bisexual individuals; however, tests of biological or psychological indicators of stress as explanations for these disparities have not been conducted.', 'Data were from the 2005-2010 National Health and Nutrition Examination Survey, and included 9662 participants; 9254 heterosexuals, 153 gays/lesbians and 255 bisexuals. Associations between sexual orientation and tobacco, alcohol, substance, and marijuana use, and body mass index, were tested using the chi-square test. Stress, operationalized as depressive symptoms and elevated C-reactive protein, was tested as mediating the association between sexual orientation and behavioral health risks. Multiple logistic regression was used to test for mediation effects, and the Sobel test was used to evaluate the statistical significance of the meditating effect.', 'Gays/lesbians and bisexuals were more likely to report current smoking (p\\u2009<\\u2009.001), a lifetime history of substance use (p\\u2009<\\u2009.001), a lifetime history of marijuana use (p\\u2009<\\u2009.001), and a lifetime period of risky drinking (p\\u2009=\\u2009.0061). The largest disparities were observed among bisexuals. Depressive symptoms partially mediated the association between sexual orientation and current smoking (aOR 2.04, 95% CI 1.59, 2.63), lifetime history of substance use (aOR 3.30 95% CI 2.20, 4.96), and lifetime history of marijuana use (aOR 2.90, 95% CI 2.02, 4.16), among bisexuals only. C-reactive protein did not mediate the sexual orientation/behavior relationship.",
            "output": [
                "Does stress mediate the relationship between sexual orientation and behavioral risk disparities?"
            ]
        },
        {
            "id": "task847-617e2505f9774939935bf18c56fd24b6",
            "input": "When a parent is terminally ill, one of the major challenges facing families is informing children of the parent's condition and prognosis. This study describes four ways in which parents disclose information about a parent's life-threatening illness to their adolescent children.\", 'We audio-recorded and transcribed 61 individual interviews with hospice patients who were recruited from a large hospice in northeastern Ohio, their spouses/partners, and their adolescent children. The interviews were coded and analyzed using a constant comparison approach.",
            "output": [
                "Is telling adolescents a parent dying?"
            ]
        },
        {
            "id": "task847-83777ba4206348919022fb58ab929ddf",
            "input": "C4 plants (e.g. corn and sugar cane) have greater (13)C enrichment than C3 plants (e.g. wheat and sugar beet).', 'To assess whether (13)C enrichment of CO2 in the breath and breast milk of women on diets based on C3 and C4 foods changes from one diet to the other.', 'Six breast-feeding women were studied at 5-6 months postpartum. They ate a controlled C4 diet on days 1 and 2 followed by a C3 diet on days 3 and 4. Diet duplicates, breast milk on days 2 and 4 and hourly breath samples were collected over 4 days. (13)C enrichment was measured by isotope-ratio mass spectrometry. Values of \u03b4(13)C were calculated from the international PDBV standard (\u03b4(13)CPDBV). Differences between means were compared by paired t test or t test for repeated measurements.', '\u03b4(13)CPDBV values were significantly higher in the C4 diet than in the C3 diet composites (p < 0.01). In breath CO2, the \u03b4(13)CPDBV value was greater on days 1 and 2 (range -15.4 to -13.2, respectively) and declined on days 3 and 4 (range -20.0 to -21.8, respectively, p < 0.01). The lipid and milk serum fractions of breast milk had significantly higher \u03b4(13)CPDBV on the C3 diet than on the C4 diet (p < 0.01).",
            "output": [
                "Is ( 13 ) C enrichment of the CO2 in breast milk and in the breath rapidly modified by changes in the ( 13 ) C content of the diet?"
            ]
        },
        {
            "id": "task847-582d0d6b84984eba9f59a662d21c209f",
            "input": "Patient-prosthesis mismatch has been identified as a risk factor for mortality after aortic valve replacement and for structural valve deterioration (SVD) in patients receiving a bioprosthetic aortic valve. The aim of the present study was to compare the incidence of aortic valve bioprosthesis replacement for SVD in patients with mismatch to a population without mismatch.', 'Three hundred eighty-seven adult patients who underwent aortic valve replacement with a bioprosthesis from 1974 to 2009 were retrospectively reviewed. Mismatch was considered to be present if the anticipated indexed effective orifice area was <0.70\\u2009cm(2) /m(2) . The median follow-up period was 7.2 years. Follow-up was 97% complete.', \"Patient-prosthesis mismatch was present in 12% of the study population (n\\u2009=\\u200947). Ten-year freedom from reoperation for aortic bioprosthesis replacement was 74.3\\u2009\u00b1\\u20093.2%. During follow-up, 111 patients underwent reoperation for aortic bioprosthesis replacement. Causes of aortic bioprosthesis replacement were SVD of the bioprosthesis (n\\u2009=\\u200996), paravalvular leak (n\\u2009=\\u200910), and acute endocarditis (n\\u2009=\\u20095). According to unadjusted Kaplan-Meier analysis, patients with mismatch had a higher incidence of aortic bioprosthesis replacement for SVD when compared with patients without mismatch (log rank test: p 0.05). This result was confirmed by multivariable Cox regression analysis, which identified two independent predictors of aortic bioprosthesis replacement for SVD: patients' age (hazard ratio (HR) 0.967) and patient-prosthesis mismatch (HR 2.161).",
            "output": [
                "Does patient-prosthesis mismatch in patients undergoing bioprosthetic aortic valve implantation increase risk of reoperation for structural valve deterioration?"
            ]
        },
        {
            "id": "task847-cbec06aee326471db0f68b024076a530",
            "input": "Inadequate nutrition in very-low-birthweight (VLBW) infants is known to be associated with growth failure and poor neurological outcomes. We aimed to investigate the association of early aggressive protein and energy intakes with weight gain and 18-month neurodevelopmental outcomes in VLBW infants.', \"A total of 90 infants among 129 infants who survived to discharge were included and divided into two groups (early aggressive nutrition [n = 52] vs conventional nutrition [n = 38]). Clinical findings were compared between the two groups and daily protein and energy intakes were collected for the first 4 weeks of life. Multiple regression analyses tested the association between weekly protein or energy intakes and the result of each category of the Denver Developmental Screening Test II at 18 months' corrected age or weight gain.\", \"The early aggressive nutrition group had higher rates of normal language development and lower rates of growth failure (<10th percentile) at both 40 weeks' and 18 months' corrected age compared to the conventional nutrition group. After controlling for the confounding variables, higher first week protein and energy intakes each independently contributed to normal language development (odds ratio [95% confidence interval]; 9.4 [1.8-49.6] per 1\\u2009g/kg of protein increase and 1.7 [1.1-2.8] per 10\\u2009kcal/kg of energy increase). Higher first-week protein intake was associated with a higher weight at 40 weeks' corrected age (r = 0.41, P = 0.005).",
            "output": [
                "Does early aggressive nutrition enhance language development in very low-birthweight infants?"
            ]
        },
        {
            "id": "task847-b8aef2704910444880974f4ba7c16043",
            "input": "Studies that investigate the subjective benefit from a bone conduction implant (BCI) sound processor in patients with single-sided sensorineural deafness (SSD) have been limited to examining short- and mid-term benefit. In the current study, we performed a survey among 44 SSD BCI users with a median follow-up time of 50 months.', 'Forty-four experienced SSD BCI users participated in the survey, which consisted of the Abbreviated Profile of Hearing Aid Benefit, the Single-Sided Deafness Questionnaire, the Short Hearing Handicap Inventory for Adults, and a self-made user questionnaire. For patients with tinnitus, the Tinnitus Questionnaire was also completed. The results of the survey were correlated with contralateral hearing loss, age at implantation, duration of the hearing loss at the time of implantation, duration of BCI use, and the presence and burden of tinnitus.', 'In total, 86% of the patients still used their sound processor. The Abbreviated Profile of Hearing Aid Benefit and the Short Hearing Handicap Inventory for Adults show a statistically significant overall improvement with the BCI. The Single-Sided Deafness Questionnaire and the user questionnaire showed that almost 40% of the patients reported daily use of the sound processor. However, the survey of daily use reveals benefit only in certain circumstances. Speech understanding in noisy situations is rated rather low, and 58% of all patients reported that their BCI benefit was less than expected.",
            "output": [
                "Do long-term subjective benefit with a bone conduction implant sound processor in 44 patients with single-sided deafness?"
            ]
        },
        {
            "id": "task847-8071fe5b148a4db4a1e76975ea1d6253",
            "input": "Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R) injury under diabetic condition has not been evaluated.', 'To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis.', 'Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-\u03baB.",
            "output": [
                "Does suv39h1 protect from myocardial ischemia-reperfusion injury in diabetic rats?"
            ]
        },
        {
            "id": "task847-ee7fba824af642258147242fdd5938eb",
            "input": "A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.', 'To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.', 'We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m2, and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.', 'In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p\\u200a=\\u200ans vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p\\u200a=\\u200a0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p\\u200a=\\u200a0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7-51, p\\u200a=\\u200a0.005 and OR 14.0, 95% c.i. 3.5-70, p\\u200a=\\u200a0.0002, respectively).",
            "output": [
                "Is risk of obstructive sleep apnea with daytime sleepiness associated with liver damage in non-morbidly obese patients with nonalcoholic fatty liver disease?"
            ]
        },
        {
            "id": "task847-23835c2a334245009071debca0b51497",
            "input": "Stimuli that predict rewarding events can control choice between future actions, and this control could be mediated by \u03b4-opioid receptors in the nucleus accumbens shell (NAc-S). Stimuli predicting the absence of important events can also guide choice, although it remains unknown whether they do so via changes in an accumbal \u03b4-opioid receptor-related process.', '\u03b4-opioid receptor-eGFP mice were trained to perform two instrumental actions that delivered different food outcomes. Choice between the two actions was then tested in the presence of stimuli paired with either the delivery or the non-delivery of each of the two outcomes. Bilateral infusions of the \u03b4-opioid receptor antagonist naltrindole into the NAc-S were used to determine the role of these receptors at the time of choice and \u03b4-opioid receptor expression in the NAc-S used to assess functional activity.', 'A stimulus predicting a specific outcome biased choice performance towards the action previously earning that same outcome. In contrast, a stimulus signalling the absence of that outcome biased performance away from the action that delivered that outcome towards actions associated with the absence of that outcome. Both effects were associated with increased \u03b4-opioid receptor expression on the membrane of cholinergic interneurons within the NAc-S. Furthermore, both effects were blocked by naltrindole infused into the NAc-S.",
            "output": [
                "Do \u03b4-Opioid receptors in the accumbens shell mediate the influence of both excitatory and inhibitory predictions on choice?"
            ]
        },
        {
            "id": "task847-f0e57426b6ed49e3b4d1bdfc956ee764",
            "input": "Clusterin (CLU) /Apolipoprotein J is a protein biosensor of oxidative stress and inflammation, which is upregulated in many pathological processes including atherosclerosis. Previous studies have shown that in aortic tissue, CLU expression increases with atherosclerotic lesion progression and it has been coupled with vascular damage and coronary artery disease. A few studies enter into CLU and carotid atherosclerosis while the apolipoprotein's expression on human carotid tissue and its association with parameters related to the disease development has not been examined. The present study was designed to reveal the relationships between the degree of CLU immunolocalization on carotid artery and demographic characteristics, blood parameters and pharmacological treatment of patients underwent internal carotid artery endarterectomy.\", \"CLU expression was detected by immunohistochemistry in 42 carotid endarterectomy specimens. Patients' serum levels of tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP) and classical parameters related to atherosclerosis such as lipid profile, as well as thrombosis related parameters such as fibrinogen, antithrombin III, protein C and protein S were determined. Demographic characteristics, smoking habits and the use of medications were recorded. Comparisons between groups were performed by students't-test and analysis of variance. Independent associations with CLU expression on carotid tissue were denoted by linear regression analysis.\", 'CLU imuunolocalization was denser in smokers than in non-smokers (p\\u2009=\\u20090.041) while it was rarefied in specimens of patients on cropidogrel treatment (p\\u2009=\\u20090.045) compared to the rest not taking this medication. Clopidogrel intake was independent predictor of lower CLU expression on carotid artery (p =0.045). CLU was positively correlated with serum TNF-a concentration (r\\u2009=\\u20090.33, p\\u2009=\\u20090.040) that was independent predictor of higher expression of the apolipoprotein (p\\u2009=\\u20090.001). IL-6, hsCRP and classical parameters related to atherosclerosis and thrombosis were not associated with CLU immunolocalization.",
            "output": [
                "Is clusterin/Apolipoprotein J immunolocalization on carotid artery affected by TNF-alpha , cigarette smoking and anti-platelet treatment?"
            ]
        },
        {
            "id": "task847-334441d6e09d44ee9789abf7d4e3628f",
            "input": "Nicotiana attenuata is attacked by larvae of both specialist (Manduca sexta) and generalist (Spodoptera exigua) lepidopteran herbivores in its native habitat. Nicotine is one of N. attenuata's important defenses. M. sexta is highly nicotine tolerant; whether cytochrome P450 (CYP)-mediated oxidative detoxification and/or rapid excretion is responsible for its exceptional tolerance remains unknown despite five decades of study. Recently, we demonstrated that M. sexta uses its nicotine-induced CYP6B46 to efflux midgut-nicotine into the hemolymph, facilitating nicotine exhalation that deters predatory wolf spiders (Camptocosa parallela). S. exigua's nicotine metabolism is uninvestigated.\", \"We compared the ability of these two herbivores to metabolize, tolerate and co-opt ingested nicotine for defense against the wolf spider. In addition, we analyzed the spider's excretion to gain insights into its nicotine metabolism. Contrary to previous reports, we found that M. sexta larvae neither accumulate the common nicotine oxides (cotinine, cotinine N-oxide and nicotine N-oxide) nor excrete them faster than nicotine. In M. sexta larvae, ingestion of nicotine as well as its oxides increases the accumulation of CYP6B46 transcripts. In contrast, S. exigua accumulates nicotine oxides and exhales less (66%) nicotine than does M. sexta. Spiders prefer nicotine-fed S. exigua over M. sexta, a preference reversed by topical or headspace nicotine supplementation, but not ingested or topically-coated nicotine oxides, suggesting that externalized nicotine but not the nicotine detoxification products deter spider predation. The spiders also do not accumulate nicotine oxides.",
            "output": [
                "Do differences in nicotine metabolism of two Nicotiana attenuata herbivores render them differentially susceptible to a common native predator?"
            ]
        },
        {
            "id": "task847-f60c81fbf4a34610a479b92621bfc198",
            "input": "To develop a method for quick identification of sun-dried and sulfur-fumigated Cimicifugae Rhizoma by Fourier transform infrared spectroscopy (FTIR).', 'The alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Cimicifugae Rhizoma were analyzed and compared by FTIR combined with second derivative infrared spectroscopy.', 'FTIR spectra showed that there were some differences in the positions of infrared absorption peaks and the relative intensities in the alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Cimicifugae Rhizoma, and the second derivative IR spectra clearly enhanced the spectral resolution of their differences. FTIR spectra showed that the new absorption peaks of Cimicifugae Rhizoma appeared and a part of original absorption peaks disappeared after sulfur-fumigation in aqueous extracts, while a lot of new absorption peaks appeared and the intensities of almost all absorption peaks significantly decreased after sulfur-fumigation in alcoholic extracts. Second derivative IR spectra showed that both sun-dried and sulfur-fumigated Cimicifugae Rhizoma extracted by water differed significantly from each other ranging from about 3 950 to 3 940 cm(-1), 3 850 to 3 800 cm(-1), 1 800 to 1 750 cm(-1), as well as from 1 400 to 1 350 cm(-1); Differences also existed between sun-dried and sulfur-fumigated Cimicifugae Rhizoma extracted by ethanol ranging from about 3 980 to 3 960 cm(-1), 3 850 to 3 800 cm(-1), and 1 500 to 1 460 cm(-1).",
            "output": [
                "Do [ Quick identification and discrimination of sun-dried and sulfur-fumigated cimicifugae rhizoma by Fourier transform infrared spectroscopy ]?"
            ]
        },
        {
            "id": "task847-b21424426e014731b885c348090d89fa",
            "input": "Human de novo single-nucleotide variation (SNV) rate is estimated to range between 0.82-1.70\u00d710(-8) mutations per base per generation. However, contribution of early postzygotic mutations to the overall human de novo SNV rate is unknown.', 'We performed deep whole-genome sequencing (more than 30-fold coverage per individual) of the whole-blood-derived DNA samples of a healthy monozygotic twin pair and their parents. We examined the genotypes of each individual simultaneously for each of the SNVs and discovered de novo SNVs regarding the timing of mutagenesis. Putative de novo SNVs were validated using Sanger-based capillary sequencing.', 'We conservatively characterised 23 de novo SNVs shared by the twin pair, 8 de novo SNVs specific to twin I and 1 de novo SNV specific to twin II. Based on the number of de novo SNVs validated by Sanger sequencing and the number of callable bases of each twin, we calculated the overall de novo SNV rate of 1.31\u00d710(-8) and 1.01\u00d710(-8) for twin I and twin II, respectively. Of these, rates of the early postzygotic de novo SNVs were estimated to be 0.34\u00d710(-8) for twin I and 0.04\u00d710(-8) for twin II.",
            "output": [
                "Do early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair?"
            ]
        },
        {
            "id": "task847-97fa5272d4a44876ab21ad06a4297f7e",
            "input": "Hydrocelectomy and spermatocelectomy are routine scrotal surgeries. A\\xa0significant number of the surgical specimens are sent for pathology analysis. However, to our knowledge no study has been done to examine outcomes and necessity, which results in significant potentially unnecessary costs to the patient and the health care system. We evaluated outcomes and surgical pathology analysis of hydroceles and spermatoceles.', 'We performed a retrospective, single institution chart review of all patients who underwent initial surgery for hydrocele or spermatocele between January 2000 and August 2013. We determined the number of cases in which a surgical specimen was sent for pathology examination. The cost for each specimen was estimated at the department of pathology.', 'A total of 264 routine scrotal cases were performed during the 14-year period. Surgical specimens were sent for pathology analysis in 102 hydrocelectomy cases (51%) and in 57 spermatocelectomy cases (90%). No pathology specimen showed any indication of malignancy. The estimated direct total cost of\\xa0pathology analysis was $49,449 in this cohort.",
            "output": [
                "Is routine pathology evaluation of hydrocele and spermatocele specimens associated with significant costs and no identifiable benefit?"
            ]
        },
        {
            "id": "task847-1d4facee60d44a86a8bda657e941532f",
            "input": "In 2012, Medicare began to tie reimbursements to inpatient complications, unplanned readmissions, and patient satisfaction, including satisfaction with pain management.', 'We aimed to identify factors that correlate with (1) pain intensity during a 24-hour period after surgery; (2) less than complete satisfaction with pain control; (3) less than complete satisfaction with staff attention to pain relief while in the hospital; and we also wished (4) to compare inpatient and discharge satisfaction scores.', 'Ninety-seven inpatients completed measures of pain intensity (numeric rating scale), satisfaction with pain relief, self-efficacy when in pain, and symptoms of depression days after operative fracture repair. The amount of opioid used in oral morphine equivalents taken during the prior 24 hours was calculated. Through initial bivariate and then multivariate analysis, we identified factors that were associated with pain intensity, less than complete satisfaction with pain control, and less than complete satisfaction with staff attention to pain relief.', 'Patients who took more opioids reported greater pain intensity (r = 0.38). No factors representative of greater nociception (fracture type, number of fractures, days from injury to surgery, days from surgery to enrollment, or type of surgery) correlated with greater pain intensity. The best multivariable model for greater pain intensity included: depression or anxiety disorder (p = 0.019), smoking (0.047), and greater opioid intake (p = 0.001). Multivariable analysis for less than ideal satisfaction with pain control included the Pain Self-Efficacy Questionnaire (PSEQ) (odds ratio [OR], 0.95; 95% CI, 0.92-0.99) alone; for less than ideal satisfaction with staff attention to pain control, the PSEQ (OR, 0.96; 95% CI, 0.92-0.99) and opioid medication use before admission (OR, 3.6; 95% CI, 1.1-12) were included.",
            "output": [
                "Does opioid use after fracture surgery correlate with pain intensity and satisfaction with pain relief?"
            ]
        },
        {
            "id": "task847-0df23f2fdf8143c091315d337dfeeceb",
            "input": "Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer.', '295 patients with locally advanced rectal cancer who were planned to undergo CRT were prospectively entered into a biobank protocol (NCT01067872). Blood samples were drawn before start of CRT. Nine biomarkers were selected, based on a previously defined hypothesis, and measured in a standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX, osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non-pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN stages).', '276 patients could be analyzed. 20.7% developed a pCR and 47.1% were classified as responders. In univariate analysis CEA (p=0.001) and osteopontin (p=0.012) were significant predictors for pCR. Taking response as outcome CEA (p<0.001), IL-8 (p<0.001) and osteopontin (p=0.004) were significant predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR 0.92, p=0.019) and CEA and IL-8 predicted for response (OR 0.97, p=0.029 and OR 0.94, p=0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and 0.68 for response; the strongest model included clinical data, PET-data and biomarkers and had an AUC of 0.81 for pCR and 0.78 for response.",
            "output": [
                "Are blood biomarkers helpful in the prediction of response to chemoradiation in rectal cancer : a prospective , hypothesis driven study on patients with locally advanced rectal cancer?"
            ]
        },
        {
            "id": "task847-1d77bac5c8c64c349f38bce0a138b79d",
            "input": "Nitric oxide (NO), mainly synthesized by inducible nitric oxide synthase (NOS2) in pathological conditions, plays an important role in cytotoxicity, inflammation and fibrosis. Elevations in exhaled NO after thoracic radiation have been reported to predict radiation-induced lung injury (RILI). This study examined whether genetic variations in NOS2 gene is associated with the risk of RILI.', 'A cohort of 301 patients between 2009 and 2011 were genotyped for 21 single nucleotide polymorphisms (SNPs) in the NOS2 gene by the Sequenom MassArray system. Kaplan-Meier cumulative probability was used to assess RILI risk and Cox proportional hazards analyses were performed to evaluate the effect of NOS2 genotypes on RILI.', 'Multivariate analysis found that three SNPs (rs2297518, rs1137933 and rs16949) in NOS2 were significantly associated with risk of RILI\u2a7e2 (P value=0.001, 0.000092, 0.001, respectively) after adjusting for other covariates. Their associations were independent of radiation dose and mean lung dose. Further haplotype analysis indicated that the ATC haplotype of three SNPs is associated with reducing the risk of developing RILI.",
            "output": [
                "Are genetic variants in inducible nitric oxide synthase gene associated with the risk of radiation-induced lung injury in lung cancer patients receiving definitive thoracic radiation?"
            ]
        },
        {
            "id": "task847-3a5ce54a8c884687b8d37d36aca0946d",
            "input": "Methotrexate (MTX) is the anchor drug in the treatment of patients with rheumatoid arthritis (RA). MTX shows effects on disease activity and mortality. However, it is unclear whether the effect of MTX on mortality depends on its effect on disease activity.', 'In a post-hoc analysis we analysed the data of our cohort established in Ratingen, Germany, and included all patients starting treatment with MTX (n=271) between 1980 and 1987. One year after baseline (BL), response to MTX treatment was assessed using a modified ACR 20 response. Follow-up data of 250 patients were available after 10 and 18 years.', 'After 1 year, there were 66% responders and 20% non-responders; only 14% had discontinued MTX treatment due to side effects or lack of efficacy. Most patients continued MTX treatment irrespective of efficacy. Ten years after BL, 61% of the patients were still treated with MTX. After 18 years, the responder-group showed a standardised mortality ratio of 1.6 compared to 3.2 for the group of non-responders. However, when adjusting for age, gender, response to MTX treatment one year after BL, number of swollen joints and comorbidities after 10 years an independent association of continued MTX treatment with lower mortality was found for the period 10 to 18 years after BL (hazard ratio (HR): 0.63, 95% confidence interval: 0.43-0.92, p=0.015).",
            "output": [
                "Is the positive influence of methotrexate on the mortality of patients with rheumatoid arthritis partly independent of its effect on disease activity : results of a re-evaluation 18 years after baseline?"
            ]
        },
        {
            "id": "task847-7dd232555f6643f99addc882e4f5bd75",
            "input": "Insulin exerts a direct action on vascular cells, thereby affecting the outcome and progression of diabetic vascular complications. However, the mechanism through which insulin signalling is impaired in the endothelium of diabetic individuals remains unclear. In this work, we have evaluated the role of the AGE precursor methylglyoxal (MGO) in generating endothelial insulin resistance both in cells and in animal models.', 'Time course experiments were performed on mouse aortic endothelial cells (MAECs) incubated with 500 \u03bcmol/l MGO. The glyoxalase-1 inhibitor S-p-bromobenzylglutathione-cyclopentyl-diester (SpBrBzGSHCp2) was used to increase the endogenous levels of MGO. For the in vivo study, an MGO solution was administrated i.p. to C57BL/6 mice for 7 weeks.', 'MGO prevented the insulin-dependent activation of the IRS1/protein kinase Akt/endothelial nitric oxide synthase (eNOS) pathway, thereby blunting nitric oxide (NO) production, while extracellular signal-regulated kinase (ERK1/2) activation and endothelin-1 (ET-1) release were increased by MGO in MAECs. Similar results were obtained in MAECs treated with SpBrBzGSHCp2. In MGO- and SpBrBzGSHCp2-exposed cells, inhibition of ERK1/2 decreased IRS1 phosphorylation on S616 and rescued insulin-dependent Akt activation and NO generation, indicating that MGO inhibition of the IRS1/Akt/eNOS pathway is mediated, at least in part, by ERK1/2. Chronic administration of MGO to C57BL/6 mice impaired whole-body insulin sensitivity and induced endothelial insulin resistance.",
            "output": [
                "Does methylglyoxal impair endothelial insulin sensitivity both in vitro and in vivo?"
            ]
        },
        {
            "id": "task847-ddb0c724755a43b0b4d7c31fdea2e0cc",
            "input": "Cysteine, a sulfur-containing amino acid, plays an important role in a variety of cellular functions such as protein biosynthesis, methylation, and polyamine and glutathione syntheses. In trypanosomatids, glutathione is conjugated with spermidine to form the specific antioxidant thiol trypanothione (T[SH]2) that plays a central role in maintaining intracellular redox homeostasis and providing defence against oxidative stress.', 'We cloned and characterised genes coding for a cystathionine \u03b2-synthase (C\u03b2S) and cysteine synthase (CS), key enzymes of the transsulfuration and assimilatory pathways, respectively, from the hemoflagellate protozoan parasite Trypanosoma rangeli.', 'Our results show that T. rangeli C\u03b2S (TrC\u03b2S), similar to its homologs in T. cruzi, contains the catalytic domain essential for enzymatic activity. Unlike the enzymes in bacteria, plants, and other parasites, T. rangeli CS lacks two of the four lysine residues (Lys26 and Lys184) required for activity. Enzymatic studies using T. rangeli extracts confirmed the absence of CS activity but confirmed the expression of an active C\u03b2S. Moreover, C\u03b2S biochemical assays revealed that the T. rangeli C\u03b2S enzyme also has serine sulfhydrylase activity.",
            "output": [
                "Is transsulfuration an active pathway for cysteine biosynthesis in Trypanosoma rangeli?"
            ]
        },
        {
            "id": "task847-abdc0fbb21394cce9ade32ba84f2d386",
            "input": "This was a prospective cohort observational study.', 'To determine the effect of dehydration and rehydration on spinal cord cross-sectional area (CSA) measurement on magnetic resonance imaging (MRI).', 'MRI Research Centre, University of British Columbia, Canada.', 'Ten healthy subjects (aged 21-32 years) were scanned on a 3T MRI scanner at four time points: (1) baseline, (2) rescan after 1\\u2009h, (3) the next day after fasting for a minimum of 14\\u2009h and (4) after rehydration with 1.5\\u2009l of water over the course of 1\\u2009h. Two independent, established semi-automatic CSA measurement techniques (one based on two-dimensional (2D) edge detection, the other on three-dimensional (3D) surface fitting) were applied to a 3D T1-weighted scan of each subject at each time point, with the operator blinded to scan order. The percentage change in CSA from baseline to each subsequent time point was calculated. One-tailed paired t-tests were used to assess the significance of the changes from baseline.', 'A decrease in CSA following dehydration was detected by both measurement methods, with a mean change of -0.654% (s.d.=0.778, P<0.05) and -0.650% (s.d.=1.071, P<0.05) for the first and second methods, respectively.",
            "output": [
                "Does dehydration affect spinal cord cross-sectional area measurement on MRI in healthy subjects?"
            ]
        },
        {
            "id": "task847-a9c78d08f1b2456296ce0edefd6d9c96",
            "input": "To investigate the relationship between mean platelet volume (MPV) and glycometabolic indices, to compare MPV according to HbA1c levels, and to analyse the difference in MPV between patients with and without microvascular complications.', 'This retrospective study was conducted on 60 Type 2 diabetic patients and 50 age- and sex-matched non-diabetic controls. We obtained demographic, clinical and laboratory data including MPV, platelet count, fasting and postprandial blood glucose (FBG and PBG), haemoglobin A1c (HbA1c), lipid profile, creatinine, systolic and diastolic blood pressure (BP) in patient and control groups, and diabetic microvascular complications including nephropathy, neuropathy, and retinopathy in the patient group. All analyses were performed using SPSS version 15.0 for Windows.', 'Mean platelet volume in the diabetic group was higher than in the control group (p = 0.001). Mean platelet volume was positively correlated with FBG and HbA1c levels (p = 0.03 and p < 0.001, respectively). It was also negatively related to platelet count (p < 0.001). Mean platelet volume in patients with HbA1c > 7% was significantly higher than those with HbA1c \u2264 7% (p < 0.001). Mean platelet volume was significantly increased in patients with retinopathy compared to those without retinopathy (p = 0.04).",
            "output": [
                "Is mean platelet volume associated with glycaemic control and retinopathy in patients with type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-7e37662be3e44540a06f3ee4fd7726a1",
            "input": "The use of digital reactive hyperemia as a measure of endothelial function among children and adolescents is becoming increasingly common. However, unexpected observations of low reactive hyperemic index values in younger children in our laboratory led us to conduct a study evaluating the influence of age, sex, height, weight, blood pressure, body mass index (BMI), and finger volume on RHI values.', 'Endothelial function, measured by digital reactive hyperemia (reactive hyperemic index: RHI) was assessed in 113 children and adolescents (mean age 12.4 \u00b1 3.8 years; 64 males), with 102 also assessed for brachial artery flow-mediated dilation (FMD) using ultrasound imaging. Associations with age, sex, height, weight, systolic and diastolic blood pressure (SBP, DBP), BMI, and finger volume were evaluated.', 'Using GLM regression, age (\u03b2 = 0.03, P = 0.014) and SBP (\u03b2 = 0.015, P = 0.004) were significantly associated with RHI. No measures were associated with FMD. In the subset of individuals with measured finger volume, age (\u03b2 = 0.025, P = 0.037) was the only measure significantly associated with log RHI. Similarly, no measures were associated with FMD.",
            "output": [
                "Is younger age associated with lower reactive hyperemic index but not lower flow-mediated dilation among children and adolescents?"
            ]
        },
        {
            "id": "task847-e7c3d5e86d65452fb12dcc12b084dd77",
            "input": "Chronic kidney disease (CKD) is a worldwide public health problem. It is very important to identify the factors that affect CKD. Previous studies have reported that serum bilirubin concentration was positively correlated with renal function in a cross-sectional study. The aim of this study was to investigate the relationship between serum bilirubin concentration and the progression of CKD.', 'A cohort study was performed on a consecutive series of 2784 subjects without CKD, defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), at baseline. We analyzed the relationship between serum total bilirubin concentration at baseline and new-onset CKD in the general population.', 'We followed the subjects for a median period of 7.7 years. There were 1157 females and 1627 males, and 231 females and 370 males developed CKD during this period. Multiple Cox regression analyses revealed that serum total bilirubin concentration (hazard ratio (HR) per 1.0 \u03bcmol/L increase 0.97 (95% CI 0.95-0.99), P = 0.0084) in addition to age, gamma-glutamyl transpeptidase (GGT), uric acid (UA), creatinine and medication for hypertension in men and serum total bilirubin concentration (HR per 1.0 \u03bcmol/L increase 0.96 (95% CI 0.93-1.00), P = 0.0309) in addition to age, GGT, alanine aminotransferase, UA, creatinine and medication for dyslipidemia in women were independent predictors of new-onset CKD, after adjusting for confounders.",
            "output": [
                "Is low serum bilirubin concentration a predictor of chronic kidney disease?"
            ]
        },
        {
            "id": "task847-860286f7f1724c8dbb0cad09fec8fe8a",
            "input": "Despite recent advances in preoperative diagnostic imaging and operative techniques, biliary variation of the donor still remains a challenge in the procurement of graft. The supraportal right bile duct (BD) variant including presentation as trifurcation is a potential trap for injuring the remnant bile duct of donor.', 'Before living/related-donor liver transplantation (LRLT), cholangiogram with magnetic resonance images of each donor was performed as a routine. After exploration of the donor before hilar dissection, intraoperative chloangiography (IOC) was routinely performed. Among the supraportal right bile duct variants, if the preoperative cholangiography showed a suspected trifurcation of the bile duct, we then performed 3 sessions of IOC during liver graft procurement, including prior to hilar dissection, before the division of bile ducts and after the division. We reviewed the cholangiogram and the postoperative laboratory data of a consecutive series of 25 donors of LRLT.', 'There was no division injury of the remnant bile duct of all of the donors.",
            "output": [
                "Is repeated introperative cholangiography helpful for donor safety in the procurement of right liver graft with supraportal right bile duct variants in living-donor liver transplantation?"
            ]
        },
        {
            "id": "task847-fedc338012c54ac081639c36e778e9aa",
            "input": "To establish the determinants of weight, length and head circumference changes during their initial hospitalization in very-low-birth-weight preterm infants.', \"A prospective cohort study was performed. Weight z-score and percentage of target dietary intakes (TDIs) were prospectively determined daily during the first 5 weeks of life in a group of preterm infants (n = 111, birth weight <1,500 g, gestational age <34 weeks). Weight, length and head circumference at 36 weeks' postmenstrual age (PMA) were recorded. A mixed effects regression model was used to evaluate changes in weight z-score during the first 5 weeks of life. Simple Pearson correlations and stepwise logistic regression were used to determine the relationship between fetal growth, illness severity, nutritional intake and growth at 36 weeks' PMA.\", \"Weight z-score decreased significantly in all infants during the first 5 weeks of life from -0.92 \u00b1 0.66 at birth to -1.89 \u00b1 0.65 at 5 weeks. The variation of weight z-score during the first 5 weeks of life was influenced by weight z-score at birth, energy and protein intakes and gestational age. Mean energy and protein intakes were 95.5 and 86.4% of TDIs. Weight z-score fell to -2.05 \u00b1 0.64 at 36 weeks' PMA. Birth weight z-score was significantly correlated with weight z-score at 36 weeks (R2 = 0.71; p < 0.001). Severity of illness influenced the weight z-score at 36 weeks.",
            "output": [
                "Is growth in preterm infants until 36 weeks ' postmenstrual age close to target recommendations?"
            ]
        },
        {
            "id": "task847-145813f5f0914ddf8b567ba022351f1d",
            "input": "This study is to assess whether transient intrauterine fluid accumulation (IUFA) first noted during controlled ovarian hyperstimulation that does not persist on the day of embryo transfer not due to any identifiable pelvic pathology has any detrimental effect on in vitro fertilization (IVF) outcome.', 'From a database of 16,900 cycles, 144 patients with transient \"physiological\" IUFA were recruited. Four hundred fifty-one consecutive patients who had male factor infertility served as the control group. The amount of IUFA classified as largest dimension in the antero-posterior (AP) plane; \u22642, 3-5 or >5\\xa0mm.', 'The mean female age, the mean number of embryos transferred and endometrial thickness on the day of hCG administration were comparable among the study and control groups. Similarly, clinical pregnancy, ongoing pregnancy and implantation rates were comparable among the study and control groups. Female age was noted to be the only significant independent predictor of ongoing pregnancy. The AP dimension of IUFA did not have any impact on pregnancy and implantation rates.",
            "output": [
                "Is transient intrauterine fluid accumulation not due to hydrosalpinx or any identifiable pelvic pathology detrimental to IVF outcome?"
            ]
        },
        {
            "id": "task847-a060e8dc96554facb566e7e8c4dcdcdb",
            "input": "This study is to investigate the role of miR-143 expression in cervical squamous cell carcinoma (SCC).', 'The expression level of miR-143 was examined by quantitative real-time PCR. Human papillomavirus (HPV) genotype was detected by HPV genotype detection kit. The expression level of bcl-2 was detected by immunohistochemistry.', 'The positive rate of HPV was 78% in the patients of cervical SCC. The most prevalent genotype was HPV16, with a positive rate of 42%. The expression level of miR-143 was significantly lower in the cervical SCC tissues than that in the normal cervical tissues (Z=-2.180, P=0.029). Down-regulated miR-143 expression was associated with tumor size, lymph node metastasis and HPV16 infection in cervical cancer patients. No significant associations were found between the expression levels of miR-143 and age, clinical stage, differentiation or lymph vascular space invasion. And, in cervical SCC patients after treatment with Taxol chemotherapy, the expression level of miR-143 was higher and the positive expression of bcl-2 protein was lower. However, the differences in expression changes of miR-143 and bcl-2 were not statistically significant (miR-143, Z=-0.763, P=0.446; bcl-2 protein, \u03c72=2.277, P=0.131).",
            "output": [
                "Is down regulation of miR-143 related with tumor size , lymph node metastasis and HPV16 infection in cervical squamous cancer?"
            ]
        },
        {
            "id": "task847-eeb0cc3b1a2a4d4e99ee14d4bfb7ff49",
            "input": "The objective of this study was to determine if delivery of wound care instruction pre-Mohs micrographic surgery versus the typical, post-Mohs surgery would allow for greater patient retention.', 'A non-blinded, randomized, controlled trial receiving institutional review board exemption from Michigan State University was conducted over a three-month period. Patients scheduled for Mohs surgery on 13 selected days were randomized into pre- versus post-procedure groups to receive wound care education.', 'This study was conducted at a dermatology practice in Saint Joseph, Michigan.', 'Fifty cognitive and literate patients greater than 18 years of age were evaluated in this study.', \"PARTICIPANTS' ability to recall instructions delivered by a Mohs surgeon in the form of digital media was assessed by a 10-question, multiple-choice exam. Additional analyses were conducted on patient's disposition around medical professionals, past experience with Mohs surgery, preference for digital media versus human instruction, and desire for home access.\", 'Pre- (n=24; score=77\u00b114%) versus post-(n=26; 83\u00b111%) procedure education displayed no significant difference (p=0.13) in overall questionnaire performance. Seventy-four percent of participants preferred video delivery as opposed to provider instruction. Thirty-four percent reported being intimidated by healthcare workers. Participant performance showed no significant change (p=0.78) with previous exposure (79\u00b119%) to Mohs surgery versus a first-time encounter (80\u00b111%).",
            "output": [
                "Does video education provide effective wound care instruction pre- or post-mohs micrographic surgery?"
            ]
        },
        {
            "id": "task847-df924d89097c44b6be055f2de5eed4aa",
            "input": "To explore the effects of continuous positive airway pressure (CPAP) treatment on the serum levels of associated inflammatory factors in patients with overlap syndrome (OS).', 'Seventy-four patients with obstructive sleep apnea syndrome (OSAS) or chronic obstructive pulmonary disease (COPD) or overlap syndrome (OS) were recruited from Department of Respirology and Affiliated Sleep Center of our hospital from March 2012 to September 2013. They were divided into OSAS (n = 25), COPD (n = 26) and OS (n = 23) groups according to the results of polysomnography (PSG) and spirometry. By enzyme linked immunosorbent assay (ELISA), the serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-\u03b1) and asymmetric dimethylarginine (ADMA) were measured and compared before and at Day 30 post-CPAP in OSAS and OS groups.', 'At pre-CPAP, there was no statistical difference in serum levels of CRP ((7.2 \u00b1 6.6),(8.4 \u00b1 6.8),(8.5 \u00b1 7.9) mg/L) and TNF-\u03b1 ((33 \u00b1 13),(52 \u00b1 34),(41 \u00b1 33) ng/L) among OSAS, COPD and OS groups (all P > 0.05).However, serum ADMA level in OSAS group were significantly lower than those in COPD group ((0.50 \u00b1 0.08) vs (0.71 \u00b1 0.31) \u00b5mol/L, P = 0.002). Compared with before and at Day 30 post-CPAP, although no significant difference existed in serum levels of ADMA (all P > 0.05), at Day 30 post-CPAP there were significantly lower serum levels of CRP ((4.5 \u00b1 4.2) and (5.5 \u00b1 4.1) mg/L) and TNF-\u03b1 levels ((31 \u00b1 9) and (35 \u00b1 24) ng/L) than those pre-CPAP in OSAS and OS groups respectively (all P < 0.05).No significant difference existed between OSAS and OS groups (all P > 0.05).",
            "output": [
                "Do [ Effects of continuous positive airway pressure treatment of inflammatory factors in patients with overlap syndrome ]?"
            ]
        },
        {
            "id": "task847-39144ae82ad9431c8e03ee2bb8bbc4ad",
            "input": "Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are considered to be crucial for cancer biology. The purpose of this study was to determine whether EMT directly led to the acquisition of tumour-initiating capacity in breast cancer cell lines.', 'Epithelial-mesenchymal transition was induced in five breast cancer cell lines and one normal breast cell line by EMT-related cytokine stimulation. Mesenchymal-epithelial transition (MET) was induced by stably overexpressing miR-200c in three mesenchymal-like breast cancer cell lines. Molecular expression and cell function analysis were performed to evaluate the effect of EMT or MET on tumour-initiating capacity and other biological characteristics.', 'The induction of EMT did not enhance tumour-initiating capacity but, instead, conferred a CD44(+)/CD24(-/low) phenotype as well as cell proliferation, migration, and resistance to doxorubicin and radiation on breast cancer cell lines. Furthermore, MET did not lead to inhibition or loss of the tumour-initiating capacity in mesenchymal-like breast cancer cell lines, but it markedly attenuated other malignant properties, including proliferation, invasion, and resistance to therapy.",
            "output": [
                "Is tumour-initiating capacity independent of epithelial-mesenchymal transition status in breast cancer cell lines?"
            ]
        },
        {
            "id": "task847-74bad4ece6ee437ea2021ee248c34597",
            "input": "Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion.', 'We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses.', 'BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin.",
            "output": [
                "Does rutin protect against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion?"
            ]
        },
        {
            "id": "task847-060512be7ffc4889ac8b9c99024aa248",
            "input": "Starch is the predominant storage compound in underground plant tissues like roots and tubers. An exception is sugar beet tap-root (Beta vulgaris ssp altissima) which exclusively stores sucrose. The underlying mechanism behind this divergent storage accumulation in sugar beet is currently not fully known. From the general presence of starch in roots and tubers it could be speculated that the lack in sugar beet tap-roots would originate from deficiency in pathways leading to starch. Therefore with emphasis on starch accumulation, we studied tap-roots of sugar beet using parsnip (Pastinaca sativa) as a comparator.', 'Metabolic and structural analyses of sugar beet tap-root confirmed sucrose as the exclusive storage component. No starch granules could be detected in tap-roots of sugar beet or the wild ancestor sea beet (Beta vulgaris ssp. maritima). Analyses of parsnip showed that the main storage component was starch but tap-root tissue was also found to contain significant levels of sugars. Surprisingly, activities of four main starch biosynthetic enzymes, phosphoglucomutase, ADP-glucose pyrophosphorylase, starch synthase and starch branching enzyme, were similar in sugar beet and parsnip tap-roots. Transcriptional analysis confirmed expression of corresponding genes. Additionally, expression of genes involved in starch accumulation such as for plastidial hexose transportation and starch tuning functions could be determined in tap-roots of both plant species.",
            "output": [
                "Are starch biosynthetic genes and enzymes expressed and active in the absence of starch accumulation in sugar beet tap-root?"
            ]
        },
        {
            "id": "task847-2f896aafa0cf412b9a29a041580c037e",
            "input": "The role of peritoneal washing cytology in determining further treatment strategies after surgery for gastric cancer remains unclear. One reason for this is the fact that optimal procedures to increase the accuracy of predicting peritoneal metastasis have not been established. The aim of this study was to evaluate the efficacy of cytology using samples harvested from two different abdominal cavity sites during gastric cancer surgery.', 'We prospectively recruited 108 patients who were clinically diagnosed with locally advanced gastric cancer (higher than cT1 stage disease). Peritoneal washing fluids were collected from the pouch of Douglas and the subphrenic area. Patients were prospectively followed up for 2 years to determine the recurrence and survival rates.', 'Thirty-three patients dropped out of the study for various reasons, so 75 patients were included in the final analysis. Seven patients (9.3%) showed positive cytology findings, of whom, three showed peritoneal recurrence. Tumor size was the only factor associated with positive cytology findings (P=0.037). The accuracy and specificity of cytology for predicting peritoneal recurrence were 90.1% and 94.2%, respectively, whereas the sensitivity was 50.0%. The survival rate did not differ between patients with positive cytology findings and those with negative cytology findings (P=0.081).",
            "output": [
                "Is conventional cytology beneficial for predicting peritoneal recurrence after curative surgery for gastric cancer : results of a prospective clinical study?"
            ]
        },
        {
            "id": "task847-557f0d6ffafb4f2085bdc62884efaa76",
            "input": "Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced secondary brain injury. However, the upstream events that initiate inflammatory responses following ICH remain elusive. Our previous studies suggested that Toll-like receptor 4 (TLR4) may be the upstream signal that triggers inflammatory injury in ICH. In addition, recent clinical findings indicated that both TLR2 and TLR4 may participate in ICH-induced brain injury. However, it is unclear how TLR2 functions in ICH-induced inflammatory injury and how TLR2 interacts with TLR4.', 'The role of TLR2 and TLR2/TLR4 heterodimerization in ICH-induced inflammatory injury was investigated in both in vivo and in vitro models of ICH.', 'TLR2 mediated ICH-induced inflammatory injury, which forms a heterodimer with TLR4 in both in vivo and in vitro models of ICH. Hemoglobin (Hb), but not other blood components, triggered inflammatory injury in ICH via assembly of TLR2/TLR4 heterodimers. MyD88 (myeloid differentiation primary response gene 88), but not TRIF (Toll/IR-1 domain-containing adaptor protein inducing interferon-beta), was required for ICH-induced TLR2/TLR4 heterodimerization. Mutation of MyD88 Arg196 abolished the TLR2/TLR4 heterodimerization.",
            "output": [
                "Does toll-like receptor 2/4 heterodimer mediate inflammatory injury in intracerebral hemorrhage?"
            ]
        },
        {
            "id": "task847-8538c52e5faf4240b86b6b1d47edff11",
            "input": "A set of 1181 E. coli strains of human fecal origin isolated in the South Moravia region of the Czech Republic was collected during the years 2007-2010. Altogether, 17 virulence determinants and 31 bacteriocin-encoding genes were tested in each of them.', 'The occurrence of bacteriocin-encoding genes was found to be positively correlated with the occurrence of E. coli virulence factors. Based on the presence of virulence factors and their combinations, E. coli strains were classified as non-pathogenic E. coli (n\\u2009=\\u2009399), diarrhea-associated E. coli (n\\u2009=\\u2009179) and ExPEC strains (n\\u2009=\\u2009603). Non-pathogenic and diarrhea-associated E. coli strains had a low frequency of bacteriocinogeny (32.6% and 36.9%, respectively). ExPEC strains encoding S-fimbriae (sfa), P-fimbriae (pap) and having genes for aerobactin biosynthesis (aer, iucC), \u03b1-hemolysis (\u03b1-hly) and cytotoxic necrosis factor (cnf1) were often bacteriocinogenic (73.8%), had a high prevalence of bacteriocin multi-producers and showed a higher frequency of genes encoding microcins H47, M, V, B17 and colicins E1, Ia and S4.",
            "output": [
                "Are bacteriocin-encoding genes and ExPEC virulence determinants associated in human fecal Escherichia coli strains?"
            ]
        },
        {
            "id": "task847-35fdc4883ad340868ee7fca3441019ef",
            "input": "The objective of this study was to determine contextual antecedents to smoking among Korean American emerging adult (KAEA) smokers using ecological momentary assessment. Based on extant theory and data documenting the importance of negative affect (NA) and social context, we examined the extent to which being with friends and NA independently and concomitantly were associated with the likelihood of subsequent smoking, over and beyond other known situational correlates of smoking.', 'Twenty-two KAEA daily smokers recorded their smoking events in real time and participated in short surveys implemented on mobile phones for 7 days. Individual, interpersonal, and situational contexts immediately preceding and during smoking events were examined in comparison to nonsmoking events using a within-subject modeling approach.', 'Both NA and being with friends independently were correlated with increased likelihood of smoking. We also found an interaction showing that the effects of NA on smoking were significant only in presence of friends.",
            "output": [
                "Do momentary negative moods and being with friends precede cigarette use among Korean American emerging adults?"
            ]
        },
        {
            "id": "task847-e12ed323b7334b1c8a0a6678a9e547d1",
            "input": "The prognostic importance of red cell distribution width (RDW) and neutrophil/lymphocyte ratio (NLR) in cardiovascular diseases has been shown. Ascending aortic dilatation (AAD) is a common cardiovascular disease and is associated with aortic wall inflammation and cystic degeneration. In this study, we aimed to investigate the relationship between serum levels of RDW, NLR and the presence of AAD.', 'Two-hundred consecutive patients with AAD diagnosed by transthoracic echocardiography were prospectively recruited and were compared to 170 age-gender- matched subjects with normal aortic diameters. Complete blood counts (CBCs) were analyzed for hemoglobin, RDW and NLR counts, as well as mean corpuscular volume (MCV). If possible, results of CBC tests within the previous two years were also included and the averages were used.', 'RDW [median 13.9, interquartile range (IQR) 1.40 vs. median 13.3, IQR 1.05%, p=0.01], NLR (median 2.04, IQR 1.09 vs. median 1.78, IQR 0.90, p=0.01) and high-sensitive C-reactive protein (hs-CRP) (median 0.60, IQR 0.80 vs. median 0.44, IQR 0.68 mg/L, p=0.01) levels were significantly higher in the AAD group compared to the control group. In univariate correlation analysis, ascending aortic diameters were correlated with RDW levels (r=0.31, p=0.01), NLR levels (r=0.15, p=0.01) and hs-CRP levels (r=0.12, p=0.03). In multivariate logistic regression analysis, increased levels of RDW and hs-CRP remained as the independent correlates of AAD in the study population. Receiver operating characteristic (ROC) curve analysis revealed that a RDW measurement higher than >13.8% predicted AAD with a sensitivity of 49.5% and a specificity of 82.8% (area under the curve [AUC] 0.681, p=0.01).",
            "output": [
                "Is red cell distribution width increased in patients with ascending aortic dilatation?"
            ]
        },
        {
            "id": "task847-3259ae994d5d432c91a527b895f7d8c0",
            "input": "Data sources The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase.\", 'Randomised controlled trials (RCTs) of orthodontic treatment to correct prominent lower front teeth were included.', 'Study screening, risk of bias assessment and data extraction were carried out independently by two reviewers. The mean differences with 95% confidence intervals were calculated for continuous data. Meta-analysis was undertaken when studies of similar comparisons reported comparable outcome measures. A fixed-effect model was used. The l(2) statistic was used as a measure of statistical heterogeneity.', 'Seven RCTs (339 patients) were included in this review. One study was assessed as at low risk of bias, three at high risk of bias and three at unclear risk. Four studies reported on the use of a facemask, two on the chin cup, one on the tandem traction bow appliance and one on mandibular headgear.One study reported on both the chin cup and mandibular headgear appliances. One study (n = 73, low quality evidence), comparing a facemask to no treatment, reported a mean difference (MD) in overjet of 4.10 mm (95% confidence interval (CI) 3.04 to 5.16; P value < 0.0001) favouring the facemask treatment.Three studies (n = 155, low quality evidence) reported ANB differences immediately after treatment with a facemask when compared to an untreated control. The pooled data showed a statistically significant MD in ANB in favour of the facemask of 3.93\u00b0 (95% CI 3.46 to 4.39; P value < 0.0001). There was significant heterogeneity between these studies (I2 = 82%). This is likely to have been caused by the different populations studied and the different ages at the time of treatment.One study (n = 73, low quality evidence) reported outcomes of the use of the facemask compared to an untreated control at three years follow-up. This study showed that improvements in overjet and ANB were still present three years post-treatment. In this study, adverse effects were reported, but due to the low prevalence of temporomandibular (TMJ) signs and symptoms no analysis was undertaken.Two studies (n = 90, low quality evidence) compared the chin cup with an untreated control. Both studies found a statistically significant improvement in ANB, and one study also found an improvement in the Wits appraisal. Data from these two studies were not suitable for pooling.A single study of the tandem traction bow appliance compared to untreated control (n = 30, very low quality evidence) showed a statistically significant difference in both overjet and ANB favouring the intervention group. The remaining two studies did not report the primary outcome of this review.",
            "output": [
                "Does weak evidence support the short-term benefits of orthopaedic treatment for Class III malocclusion in children?"
            ]
        },
        {
            "id": "task847-a7cff71ce5a944b69d1f61c04d7ec498",
            "input": "Cochrane Oral Health Group's Trials Register, CENTRAL, Medline via PubMed and EMBASE; no restrictions on language, published before February 1st 2013.\", 'Observational studies reporting outcomes from irradiated and non-irradiated patients were eligible for inclusion as were randomised controlled trials (RCTs) and controlled clinical trials (CCTs) assessing irradiated patients submitted to different implant-based treatment protocols.', \"Screening of titles, abstracts and full texts was by two reviewers, with disagreements resolved through discussion, consensus, or failing this by consultation with a third reviewer. Data extraction was in duplicate and attempts were made to contact authors for missing data. Risk of bias was assessed using adapted versions of the Cochrane Collaboration's tool (for RCTs and CCTs) and the Newcastle-Ottawa scale for observational studies.\", 'Fifteen trials with 10,150 implants were included with 1,689 (14.3%) placed in irradiated mouths. There were 13 case series and two RCTs. three of the studies were on hyperbaric oxygen (HBO) therapy. Neither of the RCTs was rated as low risk of bias. Mean survival rates ranged from 46.3% to 98% with pooled estimates showing that implant failure was statistically significantly higher in irradiated patients compared to patients who had not undergone radiotherapy (an increase of 174%) with a risk ratio of 2.74 (95% confidence interval {CI}: 1.86, 4.05; p<0.00001). In maxillary sites, the risk ratio was 5.96 (95% CI:2.71, 13.12;p<0.00001) with the risk of loss increasing to 496%. Hyperbaric oxygen therapy did not reduce the risk of implant failure showing a risk ratio of 1.28 (95% CI:0.19, 8.82).",
            "output": [
                "Do radiotherapy associated with higher rates of dental implant loss?"
            ]
        },
        {
            "id": "task847-a0619e078c5d4f3385c4b77f670b72cf",
            "input": "To evaluate the effectiveness of 4 procedures to disinfect implant surfaces intentionally inoculated with bacteria and afterward to evaluate osteoblast viability to the disinfected implant surfaces.', 'Eighty-eight commercially pure Osseotite and Nanotite titanium implant discs were inoculated with Porphyromonas gingivalis. The implant surfaces were disinfected with EDTA, tetracycline, citric acid, or neodymium-doped yttrium aluminum garnet (Nd:YAG) laser. The implant discs were then placed in cultures of osteoblast cells.', 'Osseotite implant discs were easier to disinfect compared with the Nanotite implant discs. Citric acid and tetracycline were the most effective solutions for the disinfection of P. gingivalis from the Osseotite implant discs.",
            "output": [
                "Do effectiveness of disinfection therapies and promotion of osteoblast growth on osseotite and nanotite implant surfaces?"
            ]
        },
        {
            "id": "task847-4deede50cd6841f598fe2f1b2cef69c1",
            "input": "To investigate whether the sequential therapy composed of high dose omeprazole and high dose amoxicillin in the first step was effective in eradication of H. pylori and whether there was a relation between effectiveness of the therapy and CYP2C19 gene polymorphism.', '134 dyspeptic patients with H. pylori were administered a modified sequential therapy composed of omeprazole 40 mg t.i.d. and amoxicillin 1000 mg t.i.d, for the first five days followed by omeprazole 20 mg b.d., metronidazole 500 mg t.i.d. and tetracycline 500 mg t.i.d, for the next five days. CYP2C19 genotype status was determined in patients. Hp eradication status was investigated by C14 UNT four weeks after treatment.', 'The eradication rates were 64.9% in ITT and 74.3% in PP analysis. In subgroup analyses, eradication rates were 73.8% and 60.8% (p: 0.145) in ITT for peptic ulcer and non-ulcer dyspepsia patients respectively and 86.1% and 69.1% (p: 0.052) in PP analysis for peptic ulcer and non-ulcer dyspepsia patients respectively. The difference was not significant. As for the CYP2C19 gene status, 81.5% of the patients had HoEM and 17.3% of the patients had HeEM, and eradication rates were 72% and 75% in ITT analysis for HoEM and HeEM respectively (p: 0.803) and 73.9% and 85.7% in PP analysis for HoEM and HeEM respectively (p: 0.347). There was not a significant difference in H. pylori eradication rates between the two groups.",
            "output": [
                "Is modified sequential Helicobacter pylori eradication therapy using high dose omeprazole and amoxicillin in the initial phase in the extensive metaboliser Turkish patients for CYP2C19 polymorphism ineffective?"
            ]
        },
        {
            "id": "task847-1ecbf56aed24464f8e222424759836af",
            "input": "Auditory processing in general and music perception in particular are hampered in adult cochlear implant (CI) users. To examine the residual music perception skills and their underlying neural correlates in CI users implanted in adolescence or adulthood, we conducted an electrophysiological and behavioral study comparing adult CI users with normal-hearing age-matched controls (NH controls). We used a newly developed musical multi-feature paradigm, which makes it possible to test automatic auditory discrimination of six different types of sound feature changes inserted within a musical enriched setting lasting only 20\\u2009min. The presentation of stimuli did not require the participants' attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN) brain responses to five feature changes but not to changes of rhythm, whereas we obtained MMNs for all the feature changes in the NH controls. Furthermore, the MMNs to deviants of pitch of CI users were reduced in amplitude and later than those of NH controls for changes of pitch and guitar timber. No other group differences in MMN parameters were found to changes in intensity and saxophone timber. Furthermore, the MMNs in CI users reflected the behavioral scores from a respective discrimination task and were correlated with patients' age and speech intelligibility. Our results suggest that even though CI users are not performing at the same level as NH controls in neural discrimination of pitch-based features, they do possess potential neural abilities for music processing. However, CI users showed a disrupted ability to automatically discriminate rhythmic changes compared with controls. The current behavioral and MMN findings highlight the residual neural skills for music processing even in CI users who have been implanted in adolescence or adulthood.",
            "output": [
                "Do residual neural processing of musical sound features in adult cochlear implant users?"
            ]
        },
        {
            "id": "task847-685fcb11433d4ea7bc79077ed850853c",
            "input": "Environmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated the mechanisms underlying the beneficial effects of immune regulatory processes induced in the skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity.', 'Effects of UVB light were analyzed in a murine model of CNS autoimmunity (experimental autoimmune encephalomyelitis). Additionally, patients with relapsing-remitting MS were treated with narrowband UVB phototherapy. Immunomodulatory effects were examined in skin biopsies, serum samples, and immune cells of the peripheral blood.', 'Regulatory T cells (Tregs), which are induced locally in the skin-draining lymph nodes in response to UVB exposure, connect the cutaneous immune response to CNS immunity by migration to the sites of inflammation (blood, spleen, CNS). Here, they attenuate the inflammatory response and ameliorate disease symptoms. Treg-inducing tolerogenic dendritic cells (DCs) were further necessary for induction of this systemic immune regulation by UVB radiation, because ablation of Langerhans cells abolished the UVB-induced phenotype. MS patients treated with UVB phototherapy showed an increase in induced Tregs and tolerogenic DCs accompanied by the downregulation of the T-cell effector cytokine interleukin 21. The treatment further induced elevated serum levels of vitamin D.",
            "output": [
                "Does ultraviolet B light attenuate the systemic immune response in central nervous system autoimmunity?"
            ]
        },
        {
            "id": "task847-ce2e746b47b240498a5118b475c39fb9",
            "input": "Electrophysiological studies demonstrate that a short atrial fibrillation cycle length (AFCL) is related with poor outcome of electrical cardioversion (ECV) of atrial fibrillation (AF). We found previously that the mechanical AFCL (AFCL-tvi) and atrial fibrillatory velocity (AFV-tvi) may be determined noninvasively using color tissue velocity imaging (TVI) and closely relates to the electrophysiological AFCL.', 'To evaluate the relation between AFCL-tvi, AFV-tvi, and success of ECV in patients with AF.', 'We prospectively studied 133 patients with persistent AF by performing echocardiography before ECV and measured the AFCL-tvi and AFV-tvi in the right atrium and left atrium. Recurrent AF was monitored.', 'Nineteen (14%) patients had failure of ECV, 42 (32%) remained in sinus rhythm after 1-year follow-up, and 72 (54%) had a recurrence of persistent AF. Patients with immediate ECV failure had a lower median AFV-tvi measured in the right atrium than did patients with a successful ECV: 0.7 cm/s (0.2-1.0 cm/s) vs. 1.7 cm/s (0.9-2.8 cm/s) (P = .008). Patients with maintenance of sinus rhythm after 1 year had a longer AFCL-tvi measured in the left atrium than did patients with recurrence of AF (150 ms vs 137 ms; P = .017) and had a higher AFV-tvi in both atria (1.4 vs. 0.9 cm/s in the left atrium; P = .013 and 2.2 vs 1.4 cm/s in the right atrium; P = .011). Multivariate analyses showed that all atrial TVI parameters were independently associated with the maintenance of sinus rhythm after 1 year.",
            "output": [
                "Is the mechanical fibrillation pattern of the atrial myocardium associated with acute and long-term success of electrical cardioversion in patients with persistent atrial fibrillation?"
            ]
        },
        {
            "id": "task847-e0a4ad99d3cd4b37b52eddaa731bc721",
            "input": "Facial dog bite injuries pose a significant public health problem.', 'Seventy-five consecutive patients (45 males, 30 females) treated solely by plastic surgery service for facial dog bite injuries at a Level I trauma center in the Denver Metro area between 2006 and 2012 were retrospectively reviewed. The following information were recorded: breed, relationship of patient to dog, location and number of wounds, the duration between injury and surgical repair and dog bite incident, type of repair, and antibiotic prophylaxis. Primary end points measured were wound infection, the need for revision surgery, and patient satisfaction.', 'Ninety-eight wounds in the head and neck region were repaired (46 children; mean age, 6.8 years) and (29 adults; mean age, 47.3 years). Twelve different breeds were identified. There was no significant association between the type of dog breed and the number of bite injuries. The duration between injury and repair ranged from 4 hours to 72 hours (mean [SD], 13.7 [10.9] hours). The majority of bite wounds (76 of 98) involved the cheek, lip, nose, and chin region. Direct repair was the most common surgical approach (60 of 98 wounds) (p < 0.05). There was no statistically significant association between wounds needing reconstruction versus direct repair according to dog breed (p = 0.25). Ten wounds required grafting. Twenty-five wounds were managed by one-stage or two-stage flaps. Only three patients (3.06 %) underwent replantation/revascularization of amputated partial lip (n = 2) and of cheek (n = 1). There was one postoperative infection. Data from five-point Likert scale were available for fifty-two patients. Forty patients were satisfied (5) with the outcome, while five patients were somewhat satisfied (4), and seven were neutral.",
            "output": [
                "Do retrospective analysis of facial dog bite injuries at a Level I trauma center in the Denver metro area?"
            ]
        },
        {
            "id": "task847-d2840885630241febba566f78cfe0c88",
            "input": "Protocols call for the start of hormonal therapy with levothyroxine after the declaration of brain death. As the hormonal perturbations occur during the process of brain death, the role of the early initiation of levothyroxine therapy (LT) to salvage organs is not well defined. The aim of this study was to evaluate the impact of early LT (before the declaration of brain death) on the number of solid organs procured per donor.', 'We performed an 8-year retrospective analysis of all trauma patients who progressed to brain death. Patients who consented for organ donation, received LT, and donated solid organs were included. Patients were dichotomized into two groups: early LT group, patients who received LT before the declaration of brain death, and late LT group, those who received LT after brain death. The two groups were compared for differences in demographics, clinical characteristics, need for vasopressor, and number of solid organ donation.', 'A total of 100 solid organ donors were identified of which, 41% (n=77) donors who received LT therapy were included. LT before the declaration of brain death was initiated in 37 patients compared with 40 patients who had it started after the declaration of brain death. There was no difference in demographics between the two groups except that patients in the early LT group were more likely to be hypotensive on presentation (54% vs. 25%, p = 0.001). Early LT therapy was associated with an increase in solid organ procurement rate (odds ratio, 1.9; 95% confidence interval, 1.4-2.7; p = 0.01). Sixty-seven patients donated a total of 291 solid organs.",
            "output": [
                "Does levothyroxine therapy before brain death declaration increase the number of solid organ donations?"
            ]
        },
        {
            "id": "task847-30000ecfec8543e68b0d57ff23a18bf0",
            "input": "Lateral compression pelvic Type I fractures in the elderly population are most often low-energy osteoporosis related fractures. Previous literature comparing pelvic fractures in young versus elderly patients called into question the general consideration of these injuries as benign injuries with favorable prognoses; however, the geriatric population older than 80 years is often underrepresented. This article focuses on the mortality and functional outcomes after low-energy pelvic fractures in a population of patients older than 80 years.', \"We prescreened potential subjects in a Level I trauma institution's electronic medical record database between January 1, 2002, and April 30, 2012, to identify isolated lateral compression Type 1 fractures treated nonoperatively in patients older than 80 years. This study was composed of a retrospective review of medical records followed by a prospective survey data collection to examine mechanisms of injury, length of hospital stay, complications, medical comorbidities, ambulatory function, living situation, pain, and 1 year mortality rates.\", 'We present a large case series of 85 patients older than 80 years and report a 1-year mortality rate of 20%. We found that patients who were household ambulators or nonfunctional ambulators were five times more likely (24.4% vs. 6.1%) to die within 1 year after injury. Multivariate logistic regression confirmed that the risk of 1-year mortality was significantly higher for household-bound patients compared with community ambulators, independent of sex, smoking, Charlson comorbidity index, or length of hospital stay.",
            "output": [
                "Is preinjury ambulatory status associated with 1-year mortality following lateral compression Type I fractures in the geriatric population older than 80 years?"
            ]
        },
        {
            "id": "task847-c41625b87c564663b92f6811bb1687fa",
            "input": "Radiography is an unreliable and insensitive tool for the assessment of structural lesions in the sacroiliac joints (SIJ). Magnetic resonance imaging (MRI) detects a wider spectrum of structural lesions but has undergone minimal validation in prospective studies. The Spondyloarthritis Research Consortium of Canada (SPARCC) MRI Sacroiliac Joint (SIJ) Structural Score (SSS) assesses a spectrum of structural lesions (erosion, fat metaplasia, backfill, ankylosis) and its potential to discriminate between therapies requires evaluation.', \"The SSS score assesses five consecutive coronal slices through the cartilaginous portion of the joint on T1-weighted sequences starting from the transitional slice between cartilaginous and ligamentous portions of the joint. Lesions are scored dichotomously (present/absent) in SIJ quadrants (fat metaplasia, erosion) or halves (backfill, ankylosis). Two readers independently scored 147 pairs (baseline, 2 years) of scans from a prospective cohort of patients with SpA who received either standard (n\\u2009=\\u200969) or tumor necrosis factor alpha (TNF\u03b1) inhibitor (n\\u2009=\\u200978) therapy. Smallest detectable change (SDC) was calculated using analysis of variance (ANOVA), discrimination was assessed using Guyatt's effect size, and treatment group differences were assessed using t-tests and the Mann-Whitney test. We identified baseline demographic and structural damage variables associated with change in SSS score by univariate analysis and analyzed the effect of treatment by multivariate stepwise regression adjusted for severity of baseline structural damage and demographic variables.\", 'A significant increase in mean SSS score for fat metaplasia (P\\u2009=\\u20090.017) and decrease in mean SSS score for erosion (P\\u2009=\\u20090.017) was noted in anti-TNF\u03b1 treated patients compared to those on standard therapy. Effect size for this change in SSS fat metaplasia and erosion score was moderate (0.5 and 0.6, respectively). Treatment and baseline SSS score for erosion were independently associated with change in SSS erosion score (\u03b2\\u2009=\\u20091.75, P\\u2009=\\u20090.003 and \u03b2\\u2009=\\u20090.40, P\\u2009<\\u20090.0001, respectively). Change in ASDAS (\u03b2\\u2009=\\u2009-0.46, P\\u2009=\\u20090.006), SPARCC MRI SIJ inflammation (\u03b2\\u2009=\\u2009-0.077, P\\u2009=\\u20090.019), and baseline SSS score for fat metaplasia (\u03b2\\u2009=\\u20090.085, P\\u2009=\\u20090.034) were independently associated with new fat metaplasia.",
            "output": [
                "Is tumor necrosis factor inhibitor therapy but not standard therapy associated with resolution of erosion in the sacroiliac joints of patients with axial spondyloarthritis?"
            ]
        },
        {
            "id": "task847-6d87eb1a8bb742d8a9fda4b5ce6bede8",
            "input": "Cytokeratin 19 is significant for indicating cancer cells, and Cyfra 21-1 is a fragment of cytokeratin 19. This retrospective study was designed to define the prognostic value of serum Cyfra 21-1 in epithelial ovarian cancers (EOC).', 'Serum Cyfra 21-1 concentration was obtained from 42 patients with EOC prior to treatment. Various prognostic aspects were examined using univariable and multivariable analyses. The standard serum marker cancer antigen 125 was measured simultaneously and compared in this analysis.', 'Serum levels of both Cyfra 21-1 and cancer antigen 125 were associated with positive retroperitoneal lymph nodes and platinum resistance; higher levels of Cyfra 21-1 (3.0\\xa0ng/mL as the cut-off) were associated with shorter disease-free survival (16 months vs. 28 months, p\\xa0=\\xa00.001) and overall survival (29 months vs. 41 months, p\\xa0=\\xa00.007) than lower levels. Further univariable analysis showed that Cyfra 21-1, poor differentiation, and retroperitoneal lymph node metastasis were related to platinum resistance and mortality. Multivariable analysis indicated retroperitoneal lymph node metastasis and serum Cyfra 21-1 were independent risk factors for both disease-free survival and overall survival.",
            "output": [
                "Is serum cytokeratin-19 fragment ( Cyfra 21-1 ) a prognostic indicator for epithelial ovarian cancer?"
            ]
        },
        {
            "id": "task847-e47e429c27914a2c8a609efaa1a5972f",
            "input": "Sphingolipids constitute bioactive molecules with functional implications in homeostasis and pathogenesis of various diseases. However, the role of sphingolipids as possible disease biomarkers in chronic liver disease remains largely unexplored. In the present study we used mass spectrometry and spectrofluorometry methods in order to quantify various sphingolipid metabolites and also assess the activity of an important corresponding regulating enzyme in the serum of 72 healthy volunteers as compared to 69 patients with non-alcoholic fatty liver disease and 69 patients with chronic hepatitis C virus infection. Our results reveal a significant upregulation of acid sphingomyelinase in the serum of patients with chronic liver disease as compared to healthy individuals (p<0.001). Especially in chronic hepatitis C infection acid sphingomyelinase activity correlated significantly with markers of hepatic injury (r=0.312, p=0.009) and showed a high discriminative power. Accumulation of various (dihydro-) ceramide species was identified in the serum of patients with non-alcoholic fatty liver disease (p<0.001) and correlated significantly to cholesterol (r=0.448, p<0.001) but showed a significant accumulation in patients with normal cholesterol values as well (p<0.001). Sphingosine, a further bioactive metabolite, was also upregulated in chronic liver disease (p<0.001). However, no significant correlation to markers of hepatic injury was identified.",
            "output": [
                "Is serum acid sphingomyelinase upregulated in chronic hepatitis C infection and non alcoholic fatty liver disease?"
            ]
        },
        {
            "id": "task847-ef20c4e362d640c8922eaaa5e5004d7d",
            "input": "Fragile X premutation carriers (fXPCs) have an expansion of 55-200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (FXTAS) often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate elevated risk for motor impairment associated with FXTAS. We tested whether inhibitory impairments are observable in fXPCs by assessing oculomotor performance.', 'Participants were males aged 18-48 years asymptomatic for FXTAS. FXPCs (n = 21) and healthy age-matched controls (n = 22) performed four oculomotor tasks. In a Fixation task, participants fixated on a central cross and maintained gaze position when a peripheral stimulus appeared. In a Pursuit task, participants maintained gaze on a square moving at constant velocity. In a Prosaccade task, participants fixated on a central cross, then looked at a peripheral stimulus. An Antisaccade task was identical to the Prosaccade task, except participants looked in the direction opposite the stimulus. Inhibitory cost was the difference in saccade latency between the Antisaccade and Prosaccade tasks.', 'Relative to controls, fXPCs had longer saccade latency in the Antisaccade task. In fXPCs, inhibitory cost was positively associated with vermis area in lobules VI-VII.",
            "output": [
                "Do eye movements reveal impaired inhibitory control in adult male fragile X premutation carriers asymptomatic for FXTAS?"
            ]
        },
        {
            "id": "task847-bb37540c53a34914ad5df7b7b2ae7563",
            "input": "Carpal tunnel syndrome is associated with sensory and motor impairments resulting from the compressed and malfunctioning median nerve. The thumb is critical to hand function, yet the pathokinematics of the thumb associated with carpal tunnel syndrome are not well understood.', 'The purpose of this study was to evaluate thumb motion abnormalities associated with carpal tunnel syndrome. We hypothesized that the ranges of translational and angular motion of the thumb would be reduced as a result of carpal tunnel syndrome.', 'Eleven patients with carpal tunnel syndrome and 11 healthy control subjects voluntarily participated in this study. Translational and angular kinematics of the thumb were obtained using marker-based video motion analysis during thumb opposition and circumduction movements.', 'Motion deficits were observed for patients with carpal tunnel syndrome even though maximum pinch strength was similar. The path length, normalized by palm width of the thumb tip for the patients with carpal tunnel syndrome was less than for control participants (opposition: 2.2 palm width [95% CI, 1.8-2.6 palm width] versus 3.1 palm width [95% CI, 2.8-3.4 palm width], p < 0.001; circumduction: 2.2 palm width [95% CI, 1.9-2.5 palm width] versus 2.9 palm width [95% CI, 2.7-3.2 palm width], p < 0.001). Specifically, patients with carpal tunnel syndrome had a deficit of 0.3 palm width (95% CI, 0.04-0.52 palm width; p = 0.022) in the maximum position of their thumb tip ulnarly across the palm during opposition relative to control participants. The angular ROM also was reduced for the patients with carpal tunnel syndrome compared with the control participants in extension/flexion for the metacarpophalangeal (opposition: 34\u00b0 versus 58\u00b0, p = .004; circumduction: 33\u00b0 versus 58\u00b0, p < 0.001) and interphalangeal (opposition: 37\u00b0 versus 62\u00b0, p = .028; circumduction: 41\u00b0 versus 63\u00b0, p = .025) joints.",
            "output": [
                "Does carpal tunnel syndrome impair thumb opposition and circumduction motion?"
            ]
        },
        {
            "id": "task847-2a1e2e709d474dee8be930f6fceebc66",
            "input": "We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness.', 'We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines.', 'Depletion of EXOSC4, RNMT, SENP6, WBSCR22, RASAL2, and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis.",
            "output": [
                "Does genome-wide study of hypomethylated and induced genes in patients with liver cancer unravel novel anticancer targets?"
            ]
        },
        {
            "id": "task847-10880c473fd049b78a41e7acf6070762",
            "input": "Low-intensity pulsed ultrasound (US) can accelerate fracture healing and osteogenic differentiation. The aim of this study was to investigate the osteogenic effect of low-intensity pulsed US on human periodontal ligament cells and to determine whether bone morphogenetic protein (BMP)-Smad signaling was involved.', 'Human periodontal ligament cells were exposed to low-intensity pulsed US at a frequency of 1.5 MHz and intensity of 90 mW/cm(2) for 20 min/d. Osteogenic differentiation was determined by assaying alkaline phosphatase (ALP) and calcium deposition. Expression of BMP-2, BMP-6, and BMP-9 was detected by real-time polymerase chain reaction analysis. Phosphorylated Smad was detected by western blotting; Smad in the cells was labeled by an immunofluorescent antibody and observed by laser-scanning confocal microscopy.', 'The optical density of ALP stimulated by US at 1.5 MHz and 90 mW/cm(2) for 20 min/d was significantly higher than in other groups (P < .01); therefore, this dosage was considered optimal for promoting osteogenic differentiation. After 13 days of US exposure, ALP increased gradually after 5 days, peaked at 11 days, and decreased at 13 days, with a significant difference compared with the control group (P < .05). Osteocalcin production increased from 9 to 13 days and peaked at 15 days, with a significant difference compared with the control group (P < .05). BMP-2 and BMP-6 increased dynamically after exposure for 13 days. BMP-2 increased 6.07-fold at 3 days, 6.39-fold at 11 days, and 5.97-fold at 13 days. BMP-6 expression increased 6.82-fold at 1 day and 51.5-fold at 3 days and decreased thereafter. BMP-9 was not expressed. Phospho-Smad1/5/8 expression was significantly increased after exposure (P< .05) and transferred from the cytoplasm into the nuclei.",
            "output": [
                "Does low-intensity pulsed ultrasound induce osteogenic differentiation of human periodontal ligament cells through activation of bone morphogenetic protein-smad signaling?"
            ]
        },
        {
            "id": "task847-ef3d5991220045fbaf560758e8c1e68f",
            "input": "The majority of patients with osteosarcoma and Ewing's sarcoma are diagnosed before skeletal maturity. Paley's multiplier is used for height prediction in healthy children, and has been suggested as a method to make growth predictions for children with osteosarcoma and Ewing's sarcoma when considering limb salvage options. To our knowledge, no evaluation of this method in this particular patient group has been performed, but a temporary growth deficit has been observed in children undergoing chemotherapy.\", \"We asked whether (1) Paley's formula reliably predicts growth in children who received polychemotherapy; (2) chemotherapy impairs growth velocity; and (3) final adult height is impaired in these patients.\", \"Retrospectively, data for 94 patients with osteosarcoma and Ewing's sarcoma were retrieved from databases of two sarcoma centers. Onset before 14 years of age in girls and 16 years in boys and a minimum followup until 18 years were required (mean, 67 months; range, 31-124 months) criteria. Exclusion criteria were the intake of growth hormones or no chemotherapy. Thirty-three patients (35%) fulfilled all inclusion criteria. Predicted adult heights were compared with actual adult height. The development of a growth deficit was evaluated for 23 children (without chemotherapy for recurrence) using age- and gender-specific standard deviation scores for height (WHO Z-scores).\", \"Height prediction using Paley's method showed a high percentage of false predictions (outside \u00b1 1 SD, 70%; outside \u00b1 2 SD, 61%). On average, the mean total height of the patients was overestimated (2.3 cm). The median absolute error of prediction was 5.0 cm (range, -17 to 8). Patients with osteosarcoma and Ewing's sarcoma showed a significant growth impairment during polychemotherapy. A catchup phase in growth before skeletal maturity was observed in patients with osteosarcoma but not with Ewing's sarcoma.",
            "output": [
                "Does paley 's multiplier method accurately predict adult height in children with bone sarcoma?"
            ]
        },
        {
            "id": "task847-330b2f13d19c421da5b58b3f8430ca3b",
            "input": "Fasting and calorie restriction are associated with a prolonged life span and an increased resistance to stress. The protective effects of fasting have been exploited for the mitigation of ischemic organ injury, yet the underlying mechanisms remain incompletely understood. Here, we investigated whether fasting protects liver against ischemia reperfusion (IR) through energy-preserving or anti-inflammatory mechanisms.', 'Fasted C57BL6 mice were subjected to partial hepatic IR. Injury was assessed by liver enzymes and histology. Raw264-7 macrophage-like cells were investigated in vitro. Sirt1 and HMGB1 were inhibited using Ex527 and neutralizing antibodies, respectively.', 'Fasting for one, but not two or three days, protected from hepatic IR injury. None of the investigated energy parameters correlated with the protective effects. Instead, inflammatory responses were dampened in one-day-fasted mice and in starved macrophages. Fasting alone led to a reduction in circulating HMGB1 associated with cytoplasmic HMGB1 translocation, aggregate formation, and autophagy. Inhibition of autophagy re-elevated circulating HMGB1 and abolished protection in fasted mice, as did supplementation with HMGB1. In vitro, Sirt1 inhibition prevented HMGB1 translocation, leading to elevated HMGB1 in the supernatant. In vivo, Sirt1 inhibition abrogated the fasting-induced protection, but had no effect in the presence of neutralizing HMGB1 antibody.",
            "output": [
                "Does fasting protect liver from ischemic injury through Sirt1-mediated downregulation of circulating HMGB1 in mice?"
            ]
        },
        {
            "id": "task847-8a66b81d1cd84798b4c6e189250ebc95",
            "input": "Peroxisome proliferator-activated receptor alpha (PPAR\u03b1) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPAR\u03b1 target gene in liver, but its function in hepatic lipid metabolism is unknown.', 'We investigated the regulation of vanin-1, and total vanin activity, by PPAR\u03b1 in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity.', 'Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPAR\u03b1 activity. In addition, activation of mouse PPAR\u03b1 regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPAR\u03b1, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPAR\u03b1 agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation.",
            "output": [
                "Does pPAR-alpha dependent regulation of vanin-1 mediate hepatic lipid metabolism?"
            ]
        },
        {
            "id": "task847-5b777a187837427a966b959bc9229928",
            "input": "Coffee consumption is associated with a reduced risk of Type\\xa02 diabetes. Our aim was to investigate if coffee intake may also reduce the risk of latent autoimmune diabetes in adults, an autoimmune form of diabetes with features of Type\\xa02 diabetes.', 'We used data from a population-based case-control study with incident cases of adult onset (\u2265\\xa035\\xa0years) diabetes, including 245 cases of latent autoimmune diabetes in adults (glutamic acid decarboxylase antibody positive), 759 cases of Type\\xa02 diabetes (glutamic acid decarboxylase antibody negative), together with 990 control subjects without diabetes, randomly selected from the population. Using questionnaire information on coffee consumption, we estimated the odds ratio of latent autoimmune diabetes in adults and Type\\xa02 diabetes adjusted for age, sex, BMI, smoking, physical activity, alcohol, education and family history of diabetes.', 'Coffee intake was inversely associated with Type\\xa02 diabetes (odds ratio\\xa00.92, 95%\\xa0CI 0.87-0.98 per cup/day). With regard to latent autoimmune diabetes in adults, the general trend was weak (odds ratio\\xa01.04, 95%\\xa0CI 0.96-1.13), but stratification by degree of autoimmunity (median glutamic acid decarboxylase antibody levels) suggested that coffee intake may be associated with an increased risk of high glutamic acid decarboxylase antibody latent autoimmune diabetes in adults (odds ratio\\xa01.11, 95%\\xa0CI 1.00-1.23 per cup/day). Furthermore, for every additional cup of coffee consumed per day, there was a 15.2% (P\\xa0=\\xa00.0268) increase in glutamic acid decarboxylase antibody levels.",
            "output": [
                "Does coffee consumption and the risk of latent autoimmune diabetes in adults -- result from a Swedish case-control study?"
            ]
        },
        {
            "id": "task847-b2e2a3148e9c46389438bdb341ca41f3",
            "input": "Glucocorticoid-induced leucine zipper (GILZ) represents an anti-inflammatory mediator, whose downregulation has been described in various inflammatory processes. Aim of our study was to decipher the regulation of GILZ in vascular inflammation.', 'Degenerated aortocoronary saphenous vein bypass grafts (n = 15), which exhibited inflammatory cell activation as determined by enhanced monocyte chemoattractrant protein 1 (MCP-1, CCL2) and Toll-like receptor 2 (TLR2) expression, showed significantly diminished GILZ protein and mRNA levels compared to healthy veins (n = 23). GILZ was also downregulated in human umbilical vein endothelial cells (HUVEC) and macrophages upon treatment with the inflammatory cytokine TNF-\u03b1 in a tristetraprolin (ZFP36, TTP)- and p38 MAPK-dependent manner. To assess the functional implications of decreased GILZ expression, we determined NF-\u03baB activation after GILZ knockdown by siRNA and found that NF-\u03baB activity and inflammatory gene expression were significantly enhanced. Importantly, ZFP36 is induced in TNF-\u03b1-activated HUVEC as well as in degenerated vein bypasses. When atheroprotective laminar shear stress was employed, GILZ levels in HUVEC increased on mRNA and protein level. Laminar flow also counteracted TNF-\u03b1-induced ZFP36 expression and GILZ downregulation. MAP kinase phosphatase 1 (MKP-1, DUSP1), a negative regulator of ZFP36 expression, was distinctly upregulated under laminar shear stress conditions and downregulated in degenerated vein bypasses.",
            "output": [
                "Does downregulation of the glucocorticoid-induced leucine zipper ( GILZ ) promote vascular inflammation?"
            ]
        },
        {
            "id": "task847-fb84c9370ed444928adf164abb8daaaa",
            "input": "More than 200,000 children each year are treated at emergency departments for injuries occurring on playgrounds. Empirically derived data are needed to elucidate factors associated with playground safety and reduce injury rates.', 'Determine if neighborhood, park and playground characteristics are significantly associated with playground safety.', 'A 24-item report card developed by the National Program for Playground Safety was used to assess playground safety at 41 public parks in a small to midsized, Midwestern city. Trained assessors evaluated the parks and playgrounds in June/July and used a standardized method to count the numbers of users. Data from the 2010 U.S. Census were used to describe the neighborhoods surrounding the parks.', 'The average safety score for all playgrounds was 77.4% which denotes acceptable safety levels. However, 17.1% of the playgrounds were potentially hazardous and in need of corrective measures. Playgrounds were safer in neighborhoods with more youth (< 18 years of age) and educated adults and in parks with better quality features. Playgrounds with fewer amenities were relatively less safe.",
            "output": [
                "Is playground Safety Associated With Playground , Park , and Neighborhood Characteristics?"
            ]
        },
        {
            "id": "task847-9507c556ab944a0897d607368c90579c",
            "input": "Although calcific aortic stenosis is common, calcification of the other three heart valves is not. The aortic valve interstitial cell (VIC) has been implicated in the pathogenesis of aortic stenosis. Proinflammatory stimulation of aortic VICs induces an osteogenic and inflammatory phenotypic change. We hypothesized that the VICs of the other heart valves do not undergo these changes. Using isolated human VICs from normal aortic, mitral, pulmonary, and tricuspid valves, our purpose was to compare the osteogenic response to proinflammatory stimulation via toll-like receptor 4 (TLR-4).', 'Aortic, pulmonic, mitral, and tricuspid (n=4 for each valve type) VICs were isolated from hearts valves explanted from patients undergoing cardiac transplantation. Cells were cultured and grown to confluence in passage 2-6 before treatment with Lipopolysaccharide (LPS) (100-200 ng/mL) for 24 or 48 h. Cells were characterized by immunofluorescent staining. TLR-4 expression was analyzed (immunoblotting, flow cytometry). Bone morphogenetic protein 2 and intercellular adhesion molecule 1 production were determined (immunoblotting). Monocyte chemoattractant protein 1 levels were determined by enzyme-linked immunosorbent assay. Statistics were by Mann-Whitney U test.', 'TLR-4 stimulation induced bone morphogenetic protein 2 production only in aortic VICs (P<0.05). Intra-cellular adhesion molecule 1 production and monocyte chemoattractant protein 1 secretion increased in a similar fashion among TLR-4-stimulated VICs from all four valves.",
            "output": [
                "Is aortic valve calcification mediated by a differential response of aortic valve interstitial cells to inflammation?"
            ]
        },
        {
            "id": "task847-d9e45a67533f4561a43d8c5c15c1ea73",
            "input": "In non-alcoholic fatty liver disease (NALFD), it has often been assumed that an elevation in serum ferritin is likely related to inflammation rather than iron overload.', 'Patients referred with NAFLD were entered into a clinical study of phlebotomy therapy. A liver biopsy with liver iron concentration was done at entry and 6 months after phlebotomy (n = 56) until the patient had a low serum ferritin or developed anemia. Serum ferritin was compared to liver iron concentration, ESR, CRP, BMI and grade of inflammation on liver biopsy.', 'Iron removed by phlebotomy in NAFLD correlated with the decrease in serum ferritin (r = 0.57, p = 0.0014) and liver iron concentration (r = 0.57, p = 0.0013). There was no significant correlations between serum ferritin and ESR, CRP or grade of liver inflammation.",
            "output": [
                "Is inflammation the cause of an elevated serum ferritin in non-alcoholic fatty liver disease?"
            ]
        },
        {
            "id": "task847-7fb807ea825e4ea9aaa465aafea8ad87",
            "input": "We examined the relationships between depressive symptoms, pain severity, and pain self-efficacy (PSE) in patients with chronic low back pain (CLBP). We hypothesized that change in depressive symptoms would significantly influence change in pain severity, and that PSE indirectly affects this relationship.', 'Participants were 109 CLBP patients in a 4-week multidisciplinary rehabilitation program for CLBP. They completed measures of PSE, depression, and pain severity at admission and discharge. Structural equation modeling was used to test the significant direct and indirect effects from pretreatment to posttreatment.', 'Change in depressive symptoms significantly predicted change in pain severity in affective (\u03b2=0.358; 95% confidence interval [CI], 0.206-0.480; P=0.006), sensory (\u03b2=0.384; 95% CI, 0.257-0.523; P=0.002), and evaluative pain (\u03b2=0.456; 95% CI, 0.285-0.605; P=0.002). The indirect effects of change in PSE partially accounted for the relationship between change in depressive symptoms and change in sensory (\u03b2=0.105; 95% CI, 0.016-0.241; P=0.023) and evaluative pain (\u03b2=0.121; 95% CI, 0.010-0.249; P=0.040). The relationship between change in depressive symptoms and change in affective pain was fully accounted for by the indirect effect of change in PSE (\u03b2=0.203; 95% CI, 0.082-0.337; P=0.002).",
            "output": [
                "Does pain self-efficacy mediate the relationship between depressive symptoms and pain severity?"
            ]
        },
        {
            "id": "task847-39af69b3339f489b8ca777aab5d55b7b",
            "input": "We have previously reported that polymorphism in the epidermal growth factor (EGF) gene is associated with pre-eclampsia and birthweight based on case-control association studies involving two single nucleotide polymorphisms (SNP). We extended that work to investigate other SNP in the EGF gene for their association with pre-eclampsia and the weight of babies at birth.', 'A population-based DNA collection was genotyped to determine whether the selected SNP were polymorphic in the study population. In total, 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for the polymorphic SNP using polymerase chain reaction/restriction fragment length polymorphism and MassARRAY Sequenom iPLEX methodology.', 'The rs3756261A, rs4444903G, rs2237051G haplotype was associated with the highest increased risk of pre-eclampsia (odds ratio: 3.70, 95% confidence interval: 1.38-9.94; P = 0.016). The rs3756261A allele was the one that contributed to this high degree of significance. The same allele was present in the haplotype rs3756261A, rs11568943G, rs2237051G, rs11569017A, rs4698803T (likelihood ratio statistic = 20.4671, d.f. = 3, P-value = 0.0001), which was associated with the lower birthweight.",
            "output": [
                "Is polymorphism in the epidermal growth factor gene associated with pre-eclampsia and low birthweight?"
            ]
        },
        {
            "id": "task847-f0cf37b78aa24f2a895464b6a8069e06",
            "input": "Tobacco use among persons with Type II diabetes exponentially increases negative health consequences and mortality rates. It is especially troubling that diabetic persons who smoke have a greater difficulty with tobacco cessation as compared to non-diabetic smokers. Diabetes is a metabolic syndrome that consists of insulin resistance due to disruptions in insulin signaling. We have previously shown that insulin depletion enhances the motivational effects of nicotine.', 'The present study expands our previous work by examining whether insulin resistance, produced by a high-fat diet (HFD) regimen, enhances the rewarding effects of nicotine, as measured by the conditioned place preference (CPP) paradigm. Rats were placed on either a regular diet (RD) or a HFD for 5 weeks, after which they were assessed for insulin resistance via blood glucose measurements after an insulin challenge. Rats then underwent a nicotine CPP study.', 'The findings revealed that HFD produced insulin resistant and non-insulin resistant animals. Interestingly, the magnitude of nicotine CPP was larger in insulin resistant rats versus RD rats. Nicotine CPP was absent in non-insulin resistant animals. A similar increase in body weight was observed in insulin resistant and non-insulin resistant rats as compared to RD rats. These findings suggest that neither the increased body weight nor the HFD per se in the insulin resistant rats contributed to the enhanced nicotine reward.",
            "output": [
                "Do insulin resistant rats display enhanced rewarding effects of nicotine?"
            ]
        },
        {
            "id": "task847-ffe5fbc2337d4c8ea0ec6e9a761c027d",
            "input": "To establish the benefits of immature reticulocyte fraction (IRF) measurement using an automated hematology cells analyzer over absolute neutrophil count (ANC) in predicting bone marrow recovery post induction chemotherapy.', 'A prospective observational study was carried out in the Departments of Pathology, Medicine, and Pediatrics, Universiti Kebangsaan Malaysia, Medical Center (UKMMC), Kuala Lumpur, Malaysia during a period of 19 months from April 2009 to December 2010 to assess the bone marrow recovery in patients with acute leukemia. A total of 22 patients in remission induction phases were enrolled in this study. The blood specimens were collected from day zero after chemotherapy, and every 3 days until patients recovered hematologically. All blood samples were measured for ANC and IRF using an automated hematology analyzer (Beckman-Coulter LH750).', 'The percentage of patients showing IRF recovery earlier than ANC recovery was 63.6% (14 out of 22 patients). There was a significant difference in the mean number of days for IRF recovery as compared with ANC recovery (14.05 and 17.18 days), p=0.005.",
            "output": [
                "Is immature reticulocyte fraction an early predictor of bone marrow recovery post chemotherapy in patients with acute leukemia?"
            ]
        },
        {
            "id": "task847-7c2b1df3b88245f6ae31f7f8268eceaf",
            "input": "Primary androgen deprivation therapy (PADT) is the most effective systemic therapy for patients with metastatic prostate cancer. Nevertheless, once PSA progression develops, the prognosis is serious and mortal. We sought to identify factors that predicted the prognosis in a series of patients with metastatic prostate cancer.', \"Two-hundred eighty-six metastatic prostate cancer patients who received PADT from 1998 to 2005 in Nara Uro-Oncology Research Group were enrolled. The log-rank test and Cox's proportional hazards model were used to determine the predictive factors for prognosis; rate of castration-resistant prostate cancer (CRPC) and overall survival.\", 'The median age, follow-up period and PSA level at diagnosis were 73 years, 47 months and 174 ng/mL, respectively. The 5-year overall survival rate was 63.0%. The multivariable analysis showed that Gleason score (Hazard ratio [HR]:1.362; 95% confidence interval [C.I.], 1.023-1.813), nadir PSA (HR:6.332; 95% C.I., 4.006-9.861) and time from PADT to nadir (HR:4.408; 95% C.I., 3.099-6.271) were independent prognostic factors of the incidence of CRPC. The independent parameters in the multivariate analysis that predicted overall survival were nadir PSA (HR:5.221; 95% C.I., 2.757-9.889) and time from PADT to nadir (HR:4.008; 95% C.I., 2.137-7.517).",
            "output": [
                "Are nadir PSA level and time to nadir PSA prognostic factors in patients with metastatic prostate cancer?"
            ]
        },
        {
            "id": "task847-9ecb85fc3e414803ad1a60b74365cdfd",
            "input": "In burn care, a well-acknowledged problem is the suboptimal scar outcome from skin grafted burn wounds. With the aim of improving this, we focused on a new technique: excision of the burn wound followed by primary closure, thereby using a skin-stretching device to stretch the adjacent healthy skin. The short- and long-term effect of Skin Stretch was compared to split skin grafting (SSG) in a randomized controlled trial.', 'Patients with burn wounds were randomized for SSG or primary wound closure using Skin Stretch. Follow-up was performed at 3 and 12 months postoperatively. The scar surface area was calculated and the scar quality was assessed, using subjective and objective measurement methods.', 'No significant differences between the SSG and the Skin Stretch group were found for scar surface area. In the Skin Stretch group, a significant reduction of the surface area from 65.4cm(2) (13.6-129.1) to 13.4cm(2) (3.0-36.6) was found at 3 months (p=0.028) and at 12 months postoperatively (65.4cm(2) (13.6-129.1) to 33.0cm(2) (8.9-63.7), p=0.046, Wilcoxon signed ranks test).",
            "output": [
                "Do skin stretching for primary closure of acute burn wounds?"
            ]
        },
        {
            "id": "task847-1a11aa81cbda4116bf7a16092d8062a5",
            "input": "It has been recognized for almost a decade that concentrations of signaling androgens sufficient to activate the androgen receptor are present in castration-resistant prostate cancer tissue. The source of these androgens is highly controversial, with three competing models proposed. We, therefore, wished to determine the androgenic potential of human benign and malignant (hormone-na\u00efve and treated) prostate tissue when incubated with various precursors and examine concomitant changes in enzyme expression.', 'Freshly harvested prostate tissue [benign, hormone-na\u00efve, and hormone-refractory prostate cancer (HRPC)] was incubated in excess concentrations of cholesterol, progesterone, DHEA, androstenedione, or testosterone for 96 hours, and steroid concentrations in the conditioned media measured by gas chromatography-mass spectroscopy. Changes in the expression of androgen synthetic and/or degradative enzymes were determined by expression microarray and qPCR. Significant changes were confirmed in an independent dataset.', 'Of the precursor molecules tested, only incubation with androstenedione gave rise to significant concentrations of signaling androgens. Although this was observed in all tissue types, it occurred to a significantly greater degree in hormone-refractory compared with hormone-na\u00efve cancer. Consistent with this, gene set enrichment analysis of the expression microarray data revealed significant upregulation of 17HSD17B activity, with overexpression of the canonical enzyme AKR1C3 confirmed by qPCR in the same samples and in a publicly available expression dataset. Importantly, we found no evidence to support a significant contribution from either the \"backdoor\" or \"5-\u03b1 dione\" pathway.",
            "output": [
                "Is canonical androstenedione reduction the predominant source of signaling androgens in hormone-refractory prostate cancer?"
            ]
        },
        {
            "id": "task847-80391ff83b3d494084c0980e5d416ba7",
            "input": "To identify microRNAs (miRNA) that predict response to anti-EGFR antibodies in patients with wild-type KRAS metastatic colorectal cancer (mCRC).', 'miRNA profiling was performed in a training set of 87 patients with mCRC refractory to chemotherapy treated with anti-EGFR antibodies. This included 33 fresh-frozen (FF) and 35 formalin-fixed paraffin-embedded (FFPE) samples retrospectively collected and 19 prospectively collected FF samples. An independent validation cohort consisting of 19 FF and 26 FFPE prospectively collected samples from patients with mCRC treated with anti-EGFR antibodies was used to confirm our findings.', 'After screening the expression of 1,145 miRNAs in FF samples from the training set, we identified that hsa-miR-31-3p expression level was significantly associated with progression-free survival (PFS). Statistical models based on miRNA expression discriminated between high and low risk of progression for both FF and FFPE samples. These models were confirmed in the validation cohort for both FF [HR, 4.1; 95% confidence interval (CI), 1.1-15.3; P < 0.04] and FFPE samples (HR, 2.44; 95% CI, 1.1-5.4; P = 0.028). The percentage of variation of RECIST criteria in the validation series was significantly associated with the expression level of hsa-miR-31-3p (r(2) = 0.49; P = 0.0035) and risk status determined by hsa-miR-31-3p expression level (P = 0.02, Kruskal-Wallis rank test). Nomograms were built and validated to predict PFS-depending on hsa-miR-31-3p expression level. Following in vitro studies, we identified 47 genes regulated by hsa-miR-31-3p.",
            "output": [
                "Is hsa-miR-31-3p expression linked to progression-free survival in patients with KRAS wild-type metastatic colorectal cancer treated with anti-EGFR therapy?"
            ]
        },
        {
            "id": "task847-0ef3ae8a1b1f411d8baac3691c5a3ec2",
            "input": "To identify genes whose depletion is detrimental to Pim1-overexpressing prostate cancer cells and to validate this finding in vitro and in vivo.', 'RNAi screening was used to identify genes whose depletion is detrimental to Pim1-overexpressing cells. Our finding was validated using shRNA or PLK1-specific inhibitor BI 2536. Xenograft studies were performed using both PLK1-knockdown cells and BI 2536 to investigate the effects of PLK1 inhibition on tumorigenesis in Pim1-overexpressing cells. Finally, PLK1 and PIM1 expression patterns in human prostate tumors were examined by immunohistochemistry using tissue microarrays.', 'We identified the mitotic regulator polo-like kinase (PLK1) as a gene whose depletion is particularly detrimental to the viability of Pim1-overexpressing prostate cancer. Inhibition of PLK1 by shRNA or BI 2536 in Pim1-overexpressing prostate cancer xenograft models resulted in a dramatic inhibition of tumor progression. Notably, Pim1-overexpressing cells were more prone to mitotic arrest followed by apoptosis due to PLK1 inhibition than control cells. Furthermore, inhibition of PLK1 led to the reduction of MYC protein levels both in vitro and in vivo. Our data also suggest that PIM1 and PLK1 physically interact and PIM1 might phosphorylate PLK1. Finally, PLK1 and PIM1 are frequently co-expressed in human prostate tumors, and co-expression of PLK1 and PIM1 was significantly correlated to higher Gleason grades.",
            "output": [
                "Does rNAi screen identify a synthetic lethal interaction between PIM1 overexpression and PLK1 inhibition?"
            ]
        },
        {
            "id": "task847-2d082f7f88234952b3cd7b78aa91bac0",
            "input": "The present study compared the efficacy of ramp incremented and ratings of perceived exertion (RPE)-clamped test protocols for eliciting maximal oxygen uptake (VO2max).', 'Sixteen trained cyclists (age 34 \u00b1 7 years) performed a ramp-incremented protocol and an RPE-clamped protocol 1 week apart in a randomized, counterbalanced order. The RPE-clamped protocol consisted of five, 2-min stages where subjects self-selected work rate and pedal cadence to maintain the prescribed RPE. After completing both test protocols subjects were asked which they preferred.', 'The mean \u00b1 SD test time of 568 \u00b1 72 s in the ramp protocol was not significantly different to the 600 \u00b1 0 s in the RPE-clamped protocol (mean difference = 32 s; p = 0.09), or was the VO2max of 3.86 \u00b1 0.73 L min(-1) in the ramp protocol significantly different to the 3.87 \u00b1 0.72 L min(-1) in the RPE-clamped protocol (mean difference = 0.002 L min(-1); p = 0.97). Furthermore, no significant differences were observed for peak power output (p = 0.21), maximal minute ventilation (p = 0.97), maximal respiratory exchange ratio (p = 0.09), maximal heart rate (p = 0.51), and post-test blood lactate concentration (p = 0.58). The VO2max attained in the preferred protocol was significantly higher than the non-preferred protocol (mean difference = 0.14 L min(-1); p = 0.03).",
            "output": [
                "Do ramp-incremented and RPE-clamped test protocols elicit similar VO2max values in trained cyclists?"
            ]
        },
        {
            "id": "task847-b1dd449d2b5445fea93f66523fa5b61b",
            "input": "Otitis media (OM) in children is the most frequent reason for physician visits in developed countries and burdens caregivers, society, and the child. Our objective was to describe the impact of OM severity on parent/caregiver quality of life (QoL).', 'Multi-institutional prospective cross-sectional study.', 'Otolaryngology, family, and pediatric practices.', 'Children 6 to 24 months old with and without a primary diagnosis of recurrent OM and their caregivers. Physicians provided patient history, and parents/caregivers completed a Family Information Form, the PedsQL Family Impact survey, the Patient Reported Outcomes Measurement Information System (PROMIS) survey, and the OM 6-item severity survey (OM-6).', 'A total of 2413 subjects were enrolled and data from 1208 patients and physician were analyzed. The average child age was 16 months, and 54% were male. The mean OM-6 score was 3.2. The mean PedsQL Family Impact score for parents was 66.9 from otolaryngology sites and 78.8 from pediatrics/family practice sites (P < .001). Higher (worse) OM-6 scores correlated significantly with worse PedsQL Family Impact scores (Pearson r = -0.512, P < .01). Similarly, increasing OM-6 scores strongly correlated with increased parental anxiety, depression, and fatigue, as well as decreased satisfaction (all P < .01).",
            "output": [
                "Does caregiver Quality of Life be Related to Severity of Otitis Media in Children?"
            ]
        },
        {
            "id": "task847-68b53e5b98dd4391a1d4761289135368",
            "input": "Total shoulder arthroplasty (TSA) results in superior clinical outcomes to hemiarthroplasty (HA); however, TSA is a more technical and invasive procedure. This study retrospectively compares perioperative complications after HA and TSA using the National Surgical Quality Improvement Program (NSQIP) database.', 'The NSQIP user file was queried for HA and TSA cases from the years 2005 through 2010. Major complications were defined as life-threatening or debilitating. All complications occurred within 30 days of the initial procedure. We performed multivariate analysis to compare complication rates between the two procedures, controlling for patient comorbidities.', 'The database returned 1,718 patients (HA in 30.4% [n = 523] and TSA in 69.6% [n = 1,195]). The major complication rates in the HA group (5.2%, n = 29) and TSA group (5.1%, n = 61) were similar (P = .706). Rates of blood transfusions for postoperative bleeding in patients undergoing HA (2.3%, n = 12) and TSA (2.9%, n = 35) were indistinguishable (P = .458). Venous thromboembolism was a rare complication, occurring in 0.4% of patients in each group (2 HA patients and 5 TSA patients, P > .999). On multivariate analysis, the operative procedure was not associated with major complications (P = .349); however, emergency case, pulmonary comorbidity, anemia with a hematocrit level lower than 36%, and wound class of III or IV increased the risk of a major complication (P < .05 for all).",
            "output": [
                "Are perioperative complications after hemiarthroplasty and total shoulder arthroplasty equivalent?"
            ]
        },
        {
            "id": "task847-24529c92ae874f4a93c1e7e9329046a7",
            "input": "The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood.', 'Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC.', 'Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma.",
            "output": [
                "Are action potentials in retinal ganglion cells initiated at the site of maximal curvature of the extracellular potential?"
            ]
        },
        {
            "id": "task847-81acccadfed448778cc004fe244c50cb",
            "input": "We aimed to explore the association between vitamin D levels and the severity, mortality and microbiological etiology of community-acquired pneumonia.', 'Vitamin D levels (both, the reservoir form 25-OH and the activated form 1,25-OH2) of 300 randomly selected patients with community-acquired pneumonia due to pre-specified pathogens included in the German competence network (CAPNETZ) study were measured. Prior to statistical analysis, values of 25-OH and 1,25-OH2 were power-transformed to achieve parametric distribution. All further analyses were performed with seasonally and age adjusted values.', 'There was only a modest (Spearman Coefficient 0.38) positive correlation between 25-OH and 1,25-OH2. For 1,25-OH2 but not 25-OH, the general linear model revealed a significant inverse correlation between serum concentration and CURB score (p\\u2009=\\u20090.011). Liver and respiratory co-morbidity were associated with significantly lower 25-OH values and renal co-morbidity with significantly lower 1,25-OH2 values. No significant differences of 1,25-OH2 or 25-OH between different pathogens (influenza virus, Legionella spp., Streptococcus pneumoniae) were detected.",
            "output": [
                "Are vitamin D deficiency in community-acquired pneumonia : low levels of 1,25 ( OH ) 2 D associated with disease severity?"
            ]
        },
        {
            "id": "task847-92d7341a2dca4e5aaff2b7cf6af1e8eb",
            "input": "The study's aim was to assess the internal reliability for the nine domains of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) to evaluate homogeneity across clinical studies and whether sample characteristics predict coefficient heterogeneity.\", 'A systematic literature review was undertaken. Internal reliability was assessed against Cronbach \u03b1 coefficient >0.70. Reliability generalization was undertaken using fixed- and random-effects models. A weighted least squares regression model was applied to determine whether baseline sample characteristics (language, percentage of women, sample size, sample means and standard deviations, and cancer type) predicted variation in \u03b1 coefficients.', 'A total of 33 studies were identified. Eight domains demonstrated good internal reliability (unweighted/weighted by sample variance). One domain, Cognitive Functioning, consistently performed poorly. In terms of moderating variables, none of the sample characteristic variables explained sample variance for the Physical or Role Functioning domains. For the other domains, language, percentage of women, and sample means and variances accounted for some of the heterogeneity observed.",
            "output": [
                "Are most domains of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 reliable?"
            ]
        },
        {
            "id": "task847-0b5ead12475a49d980809b978c7f4507",
            "input": "The aim of this article is to develop the Spanish adaptation of the internal functioning of Work Teams Scale (QFI-22).', 'The scale was adapted from the French version, and was applied to a sample of 1,055 employees working for firms operating in Spain. The article analyses the internal structure (exploratory and confirmatory factor analysis) and internal consistency, and provides convergent validity evidence of the scale.', 'The QFI-22 scale shows the same internal structure as the original. Factor analysis confirmed the existence of two factors: interpersonal support and team work management, with good internal consistency coefficients (\u03b11 = .93, \u03b12 = .92). Regarding validity evidence, the QFI-22 scale has significant correlations with other correlates and alternative scales used for comparison purposes. The two factors correlated positively with team vision, participation safety, task orientation and support for innovation (Team Climate Inventory, TCI scale), with progressive culture (Organisational Culture, X-Y scale), and with creating change, customer focus and organisational learning (Denison Organizational Culture Survey, DOCS scale). In contrast, the two factors correlated negatively with traditional culture (X-Y scale).",
            "output": [
                "Does spanish adaptation of the internal functioning of the Work team Scale ( QFI-22 )?"
            ]
        },
        {
            "id": "task847-d761c1cdae1a4344921b97d8dd25011a",
            "input": "The purpose of this qualitative study was to explore the meaning of the phrase \"image of the nurse\" in the context of the desired brand experience of assurance.', 'A brand is a promise that lives in the minds of consumers. Nurses play a key role in delivering on the brand promise of a hospital.', 'Using focus groups, the authors applied a deductive approach to generate data. Discussion transcripts were analyzed by establishing codes and identifying themes.', 'The most frequent comment from participants was that for nurses to communicate assurance, they must 1st be clean, well groomed, and understated in overall appearance. Nurse behaviors that reassure patients include being present with patients, helping patients know what to expect, and demonstrating a consistent team approach.",
            "output": [
                "Is image more than a uniform : the promise of assurance?"
            ]
        },
        {
            "id": "task847-01e0164b71224da08604293a99980af2",
            "input": "Epidemiologic studies remain inconclusive on whether the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) increases mucosal HIV shedding and transmissibility. Nonhuman primate models may help to determine the effects of DMPA on acute HIV replication.', 'We defined a physiologic dose of DMPA in macaques and assessed the impact of DMPA on acute simian HIV (SHIV) replication.', 'Pigtail macaques received 1-30 \\u200amg of DMPA intramuscularly followed by measurements of progesterone and medroxyprogesterone acetate (MPA). Vaginal epithelial thickness, number of cell layers and density of intraepithelial CD3 cells were measured. The effect of DMPA on SHIV viremia and genital virus shedding was investigated in six pigtail macaques infected during monthly treatment cycles with 3 \\u200amg DMPA. Six DMPA-untreated macaques were controls.', 'Plasma MPA concentrations directly correlated with changes in epithelial thickness (correlation = 0.84; P < 0.001) and density of intraepithelial CD3 cells (correlation = 0.41; P = 0.02). A 3 mg DMPA dose recapitulated plasma MPA concentrations and changes in vaginal epithelial thickness seen in women. DMPA-treated and untreated macaques showed similar peak plasma viremia and RNA area under the curve values over 12 weeks (P = 0.94), although treated macaques had higher odds of having virus being detected in plasma (odds ratio 6.6, P = 0.02). Rectal and vaginal virus shedding was similar between treated and untreated macaques (P \\u200a= 0.72 and P = 0.53, respectively).",
            "output": [
                "Do physiologic doses of depot-medroxyprogesterone acetate increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques?"
            ]
        },
        {
            "id": "task847-6608a0823fc24aaa925ad795a11dd42b",
            "input": "To determine the prevalence of haemorrhoids in women with pelvic vein reflux, identify which pelvic veins are associated with haemorrhoids and assess if extent of pelvic vein reflux influences the prevalence of haemorrhoids.', 'Females presenting with leg varicose veins undergo duplex ultrasonography to assess all sources of venous reflux. Those with significant reflux arising from the pelvis are offered transvaginal duplex ultrasound (TVS) to evaluate reflux in the ovarian veins and internal Iliac veins and associated pelvic varices in the adnexa, vulvar/labial veins and haemorrhoids. Patterns and severity of reflux were evaluated.', 'Between January 2010 and December 2012, 419 female patients with leg or vulvar varicose vein patterns arising from the pelvis underwent TVS. Haemorrhoids were identified on TVS via direct tributaries from the internal Iliac veins in 152/419 patients (36.3%) and absent in 267/419 (63.7%). The prevalence of the condition increased with the number of pelvic trunks involved.",
            "output": [
                "Are haemorrhoids associated with internal iliac vein reflux in up to one-third of women presenting with varicose veins associated with pelvic vein reflux?"
            ]
        },
        {
            "id": "task847-8ee92ff2238b4112bff834afdcc193f7",
            "input": "To determine the expression of proteasome aotivator gamma (REGgamma) in human lung cancer tissues and cell lines and its association with malignant biological behaviors.', 'Immunohistochemistry (IHC) was used to detect the expression of REGgamma in lung cancer and normal lung tissues. The expressions of REGgamma in lung cancer cells and normal epithelial cells were determined by Western blot. The H1975 lung cancer stable cell lines with different levels of REGgamma expression were constructed and their proliferations were evaluated by MTT assay. PI staining was used to assess the influence of REGgamma on cell growth cycle. The effect of REGgamma on the migration of lung cancer cells were observed with the cell scratch experiment.', 'Lung cancer tissues had significantly higher levels of REGgamma expression than normal tissues. Similarly, lung cancer cell lines showed higher levels of REGgamma expression than the normal epithelial cell line. The overexpression of REGgamma enhanced cancer cell proliferations (P < 0.05), promoted more cells into the S+G2/M phase (P < 0.05) and promoted the migration of cancer cells (P < 0.05). All of these effects were reversed after suppression of REGgamma.",
            "output": [
                "Does [ REGgamma promote malignant behaviors of lung cancer cells ]?"
            ]
        },
        {
            "id": "task847-695f6fbd1cbf46f7912b247048972b1d",
            "input": "Opioid-induced spastic paraplegia after transient spinal cord ischemia during aortic surgery has been reported. Opioids modulate neurotransmission through mu (\u03bc) opioid receptors (MORs) in the spinal ventral horn. However, their effects during ischemic insult are not understood.', 'The effects of the selective \u03bc agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO) on ischemia-induced agonal currents were examined in the spinal lamina IX neurons of neonatal rats by using the whole-cell patch-clamp technique. Ischemia was simulated in vitro by oxygen/glucose deprivation.', 'DAMGO (1 \u03bcM) produced outward currents in ~60% of spinal lamina IX neurons at a holding potential of -70 mV. Superfusion with ischemia-simulating medium elicited an agonal current. The latency was 457 \u00b1 18 s. Despite its neuromodulatory effects, DAMGO did not significantly change the latencies of the agonal currents with (440 \u00b1 23 s) or without (454 \u00b1 33 s) DAMGO-induced currents.",
            "output": [
                "Does the mu opioid receptor activation affect ischemia-induced agonal currents in rat spinal ventral horn?"
            ]
        },
        {
            "id": "task847-9a291d1db70c4d60a65a795b610b7e04",
            "input": "Most of the information in Electronic Health Records (EHRs) is represented in free textual form. Practitioners searching EHRs need to phrase their queries carefully, as the record might use synonyms or other related words. In this paper we show that an automatic query expansion method based on the Unified Medicine Language System (UMLS) Metathesaurus improves the results of a robust baseline when searching EHRs.', 'The method uses a graph representation of the lexical units, concepts and relations in the UMLS Metathesaurus. It is based on random walks over the graph, which start on the query terms. Random walks are a well-studied discipline in both Web and Knowledge Base datasets.', 'Our experiments over the TREC Medical Record track show improvements in both the 2011 and 2012 datasets over a strong baseline.",
            "output": [
                "Does improving search over Electronic Health Records using UMLS-based query expansion through random walk?"
            ]
        },
        {
            "id": "task847-5270d1302de849c9b07c2f49ac2e4a71",
            "input": "Hospital case volume has been shown to be a predictor of patient mortality for treatment for various cancers. The influence of hospital case volume on malignant melanoma survival and treatment utilization is unknown.', 'We used the Surveillance, Epidemiology, and End Results-Medicare linked databases to identify patients aged 65 years or older diagnosed with metastatic melanoma between 2000 and 2009. We analyzed claims data to ascertain cancer treatment variation by hospital case volume. Overall survival was evaluated using propensity score methods.', 'Among 1438 patients, 612 (42.6%) were treated in low-volume hospitals (\u22645 patients) after receiving their diagnosis, 479 (33.3%) were treated in intermediate-volume hospitals (6 to 10 patients), and 347 (24.1%) were treated in high-volume hospitals (>10 patients). In Cox proportional hazards models, treatment in a high-volume hospital after propensity score adjustment was associated with a significant improvement in survival when adjusting for other characteristics (intermediate volume: hazard ratio [HR]=0.70, P=0.0007; high volume: HR=0.63, P<0.0001). Patients treated in high-volume hospitals were less likely to receive chemotherapy, surgery, and/or radiation therapy after a metastatic melanoma diagnosis.",
            "output": [
                "Does hospital Case Volume be Associated With Improved Survival for Patients With Metastatic Melanoma?"
            ]
        },
        {
            "id": "task847-c41ef83bbcd14594a5796817455c40ed",
            "input": "Sodium octanoate (Oct) and N-acetyl-l-tryptophan (N-AcTrp) are widely used as stabilizers during pasteurization and storage of albumin products. However, exposure to light photo-degrades N-AcTrp with the formation of potentially toxic compounds. Therefore, we have examined the usefulness of N-acetyl-l-methionine (N-AcMet) in comparison with N-AcTrp for long-term stability, including photo stability, of albumin products.', 'Recombinant human serum albumin (rHSA) with and without additives was photo-irradiated for 4weeks. The capability of the different stabilizers to scavenge reactive oxygen species (ROS) was examined by ESR spectrometry. Carbonyl contents were assessed by a spectrophotometric method using fluoresceinamine and Western blotting, whereas the structure of rHSA was examined by SDS-PAGE, far-UV circular dichroism and differential scanning calorimetry. Binding was determined by ultrafiltration.', 'N-AcMet was found to be a superior ROS scavenger both before and after photo-irradiation. The number of carbonyl groups formed was lowest in the presence of N-AcMet. According to SDS-PAGE, N-AcMet stabilizes the monomeric form of rHSA, whereas N-AcTrp induces degradation of rHSA during photo-irradiation. The decrease in \u03b1-helical content of rHSA was the smallest in the presence of Oct, without or with N-AcMet. Photo-irradiation did not affect the denaturation temperature or calorimetric enthalpy of rHSA, when N-AcMet was present.",
            "output": [
                "Is n-acetyl-l-methionine a superior protectant of human serum albumin against photo-oxidation and reactive oxygen species compared to N-acetyl-L-tryptophan?"
            ]
        },
        {
            "id": "task847-ba8efe23718e43419258edd17fb88312",
            "input": "Oral submucous fibrosis is a pre-malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial-lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors.', 'Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase-contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl-thiazol-tetrazolium assay.', 'Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333\\xa0\u03bcg/ml or more. Ultrastructural features of cellular stress were seen after 24-h treatment with 111\\xa0\u03bcg/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4\\xa0h with arecoline at 333\\xa0\u03bcg/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24\\xa0h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl-thiazol-tetrazolium assays.",
            "output": [
                "Is arecoline cytotoxic for human endothelial cells?"
            ]
        },
        {
            "id": "task847-5b8a7d61aa8941d5a9ee3b6106965e3e",
            "input": "The present study investigated how parents and peers interact in promoting or delaying Dutch adolescents' sexual initiation and intention and focused specifically on parents as moderators of peer influence.\", \"Using a longitudinal design, two waves of online questionnaire data were collected among 900 Dutch adolescents (M = 13.8 years at T1), who were sexually inexperienced at baseline. At T1, participants reported on three types of perceived sexual peer norms: friends' sexual behaviors (descriptive norms), friends' sexual attitudes (injunctive norms), and experienced peer pressure to have sex. They also rated two parenting aspects at T1: the general quality of their relationship with parents and the frequency of sexuality-specific communication with their parents. Six months later, the participants reported on their experience with different sexual behaviors ranging from naked touching or caressing to intercourse and their intention to have sex in the next school year.\", \"Relationship quality with parents was significantly associated with both outcomes, with a higher relationship quality predicting smaller odds of sexual initiation and less intention to have sex. Two significant interaction effects showed that frequent sexual communication with parents significantly reduced the effects of sexually active friends and experienced peer pressure on adolescents' intention to have sex.",
            "output": [
                "Do parents as moderators of longitudinal associations between sexual peer norms and Dutch adolescents ' sexual initiation and intention?"
            ]
        },
        {
            "id": "task847-ff18fdc133354e2d9657902704df3c5b",
            "input": "Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. This study aimed to investigate the atherogenic mechanism of BPA using a PXR-humanized mouse model.', 'A PXR-humanized ApoE deficient (huPXR\u2022ApoE(-/-)) mouse line was generated that respond to human PXR ligands and feeding studies were performed to determine the effects of BPA exposure on atherosclerosis development. Exposure to BPA significantly increased atherosclerotic lesion area in the aortic root and brachiocephalic artery of huPXR\u2022ApoE(-/-) mice by 104% (P<0.001) and 120% (P<0.05), respectively. By contrast, BPA did not affect atherosclerosis development in the control littermates without human PXR. BPA exposure did not affect plasma lipid levels but increased CD36 expression and lipid accumulation in macrophages of huPXR\u2022ApoE(-/-) mice.",
            "output": [
                "Does bisphenol A increase atherosclerosis in pregnane X receptor-humanized ApoE deficient mice?"
            ]
        },
        {
            "id": "task847-eea087ea8994490e8ae04a5d5b65eae5",
            "input": "Altered nitric oxide (NO) signaling has been associated with the pathophysiology of Bipolar Disorder (BD), directly affecting neurotransmitter release and synaptic plasticity cascades. Lithium has shown to regulate NO levels in preclinical models. However, no study has addressed peripheral NO levels in unmedicated BD. Also, lithium's effects on NO levels have not been studied in humans.\", 'Plasma NO was evaluated in subjects with BD I and II during a depressive episode (n\\xa0=\\xa026). Subjects had a score of \u226518 in the 21-item Hamilton Depression Rating Scale and were followed-up during a 6-week trial with lithium. Plasma NO levels were also compared to matched healthy controls (n\\xa0=\\xa028). NO was determined by chemiluminescence method.', 'Lithium treatment significantly increased plasma NO levels after 6 weeks of treatment in comparison to baseline levels in bipolar depression (p\\xa0=\\xa00.016). Baseline NO levels during depressive episodes showed no difference when matching up to healthy controls (p\\xa0=\\xa00.66).",
            "output": [
                "Does lithium increase nitric oxide levels in subjects with bipolar disorder during depressive episodes?"
            ]
        },
        {
            "id": "task847-3a621219c38047dca7790e5475be0901",
            "input": "Cardiac rupture is a catastrophic complication that occurs after acute myocardial infarction (MI) and, at present, there are no effective pharmacological strategies for preventing this condition. Here we investigated the effect of the angiotensin II receptor blocker olmesartan (Olm) on post-infarct cardiac rupture and its underlying mechanisms of action.', 'C57Bl/6 mice with MI were treated with Olm, aldosterone (Aldo) or vehicle. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with angiotensin II (Ang II), RNH6270 (active ingredient of Olm) or Aldo.', 'The mortality rate and incidence of cardiac rupture in MI mice during the first week in the Olm-treated group were significantly lower than in the vehicle-treated group. Olm or RNH6270 reduced myeloperoxidase staining in the infarcted myocardium, decreased apoptosis in cultured cardiomyocytes and fibroblasts, as assessed by Hoechst staining and TUNEL assay, attenuated the accumulation of p53 and phosphorylated p53 and cleaved caspase 3 induced by MI or Ang II, as assessed by Western blotting, and up-regulated growth differentiation factor-15 (GDF-15). In cultured cardiomyocytes and fibroblasts, treatment with Ang II, Aldo or anoxia significantly down-regulated the expression of GDF-15.",
            "output": [
                "Does olmesartan prevent cardiac rupture in mice with myocardial infarction by modulating growth differentiation factor 15 and p53?"
            ]
        },
        {
            "id": "task847-c84f2334084d49e9b24b13aa56f612f7",
            "input": "The efficacy and feasibility of laparoscopic surgery (LAP) for gastric GISTs >5 cm has not been adequately assessed. Here we investigated the clinical outcomes of these patients.', 'Twenty-seven consecutive patients who underwent resection for gastric GISTs >5 cm were enrolled in this retrospective study. We assessed the tumor characteristics, surgical outcomes, tumor recurrence, and patient survival in the open surgery (OPEN) group and in the LAP group.', 'The tumor size in the OPEN group was larger than that in the LAP group, but there were no differences in the mitotic count. There were no differences in operative complications. Finally, there were no differences in the disease-free and no patients in the LAP group died.",
            "output": [
                "Is surgical strategy for the gastric gastrointestinal stromal tumors ( GISTs ) larger than 5 cm : laparoscopic surgery feasible , safe , and oncologically acceptable?"
            ]
        },
        {
            "id": "task847-249aa31ed149488d83decfa59016eab7",
            "input": "Serum \u03b3-glutamyltranspeptidase (GGT) level, which is often elevated in hepatocellular carcinoma (HCC), has now been found to be an oxidative stress marker which correlates with inflammation in the extracellular hepatic microenvironment. The aim of this study was to investigate the prognostic significance of GGT serum levels in patients undergoing radiofrequency ablation (RFA) therapy for the treatment of HCC.', 'This retrospective study included 254 patients with small liver cancer (tumor of \u22645 cm in diameter and nodule of \u22643 cm) who had been treated with RFA. Baseline serum GGT was examined before therapy, and overall survival (OS) and recurrence-free survival were evaluated by the Kaplan-Meier method. Univariate and multivariate analyses were used to analyze the significance of GGT and other serum markers as prognostic factors.', 'After a median follow-up of 27 months, 51 patients had died and 123 had hepatic recurrence. After treatment with RFA, HCC patients with elevated GGT had a shorter OS versus those with normal GGT level (p = 0.001); they also had higher recurrence (p = 0.001). On multivariate analysis, albumin (p = 0.003), GGT (p = 0.035), and tumor size (p = 0.027) were independent risk factors for survival, and GGT (p = 0.010) and tumor size (p = 0.026) were significant risk factors for recurrence.",
            "output": [
                "Is \u03b3-Glutamyltranspeptidase a prognostic marker of survival and recurrence in radiofrequency-ablation treatment of hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-8eb466f5f8454b7a8302f1b36c6e27c6",
            "input": "This study aimed to evaluate the long-term outcomes and the soft-tissue response to osseous genioplasty in patients with chin retrusion caused by early life facial burn injury.', 'Twenty-two consecutive patients with retrusive chin as a result of severe childhood facial burn were included in this study. Cephalometric analysis and photographs were used to assess the patients for eligibility of a surgical correction. Horizontal hard-tissue advancement and soft-tissue responses were measured as the primary outcomes at the early and late postoperative follow-up visits.', 'A total of 22 patients fulfilled the study requirements. Average preoperative distance between the pogonion, as the most anterior point of the anterior mandibular contour, and a perpendicular line connecting the nasion and the supramental point of the mandible was 0.82 \u00b1 1.1 mm, which increased significantly to 7.8 \u00b1 0.8 mm after genioplasty (p < 0.0001). Soft tissue was repositioned on average 6.1 \u00b1 0.4 mm anteriorly on average, which is in comparison with the amount of chin skeleton advancement, and a response ratio of 0.8:1 was calculated at late follow-up.",
            "output": [
                "Do soft-tissue response rate to chin skeletal advancement in patients with lower facial burn scar?"
            ]
        },
        {
            "id": "task847-3556eae999034f81b9e28986538cb278",
            "input": "Glucocorticoids (GCs), including the synthetic GC derivate dexamethasone, are widely used as immunomodulators. One of the numerous side effects of dexamethasone therapy is hypertension arising from reduced release of the endothelium-derived vasodilator nitric oxide (NO).', 'Herein, we described the role of dexamethasone and its glucocorticoid receptor (GR) in the regulation of NO synthesis in vitro using the mouse myocardial microvascular endothelial cell line, MyEND. GC treatment caused a firm decrease of extracellular NO levels, whereas the expression of endothelial NO synthase (eNOS) was not affected. However, GC application induced an impairment of tetrahydrobiopterin (BH4 ) concentrations as well as GTP cyclohydrolase-1 (GTPCH-1) expression, both essential factors for NO production upstream of eNOS. Moreover, dexamethasone stimulation resulted in a substantially decreased GR gene and protein expression in MyEND cells. Importantly, inhibition of proteasome-mediated proteolysis of the GR or overexpression of an ubiquitination-defective GR construct improved the bioavailability of BH4 and strengthened GTPCH-1 expression and eNOS activity.",
            "output": [
                "Does inhibition of proteasome-mediated glucocorticoid receptor degradation restore nitric oxide bioavailability in myocardial endothelial cells in vitro?"
            ]
        },
        {
            "id": "task847-91e0a1e6e1f546dabfcb00bbf7a63415",
            "input": "Few studies have investigated factors influencing participation rates for minority children with a chronic disease in clinical trials. The Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial provides an opportunity to study the impact of demographic and socio-economic factors on randomization in a clinical trial among Black children. Our primary objective was to characterize the factors associated with successful randomization of children with sickle cell disease (SCD) and silent cerebral infarct (SCI) in the SIT Trial after initial consent.', 'Differences in socio-economic and demographic variables, family history and disease-related variables were determined between eligible participants who were successfully randomized and those who were not randomized following initial consent. Head of household educational level and family income were examined separately for US versus non-US sites.', 'Of 1,176 children enrolled in the SIT Trial, 1,016 (86%) completed screening. Of 208 (20%) children with qualifying SCI on pre-randomization MRI, 196 (94%) were successfully randomized. There were no differences in socio-economic, demographic, or disease-related variables between children who were or were not randomized. Participants from non-US sites were more likely to be randomized (22% vs. 12%, P = 0.011); although, randomization by country was associated with neither head of household education nor family income.",
            "output": [
                "Is randomization associated with socio-economic and demographic factors in a multi-center clinical trial of children with sickle cell anemia?"
            ]
        },
        {
            "id": "task847-3f70fd3b11b44ca1aa2403454d998925",
            "input": "To describe technical challenges encountered using the Ovation endograft for abdominal aortic aneurysms and suggest tips and maneuvers for successful management.', \"Deployment of the Ovation's unsupported main body is often associated with the anteroposterior arrangement of the limb gates instead of the usual side-by-side configuration, rendering contralateral catheterization challenging. Successful catheterization of the contralateral limb can be confirmed by lateral deviation of the ipsilateral stiff guidewire caused by balloon inflation within the contralateral limb. Moreover, failure to cannulate the contralateral limb gate due to persistent impingement of the guidewire or compromise of the inflated rings can be overcome using the transbrachial antegrade approach.",
            "output": [
                "Does technical challenge encountered during deployment of the ovation abdominal aortic stent-graft system?"
            ]
        },
        {
            "id": "task847-db675d85d7584e4fb37ad90250cbbbb8",
            "input": "To evaluate if return of spontaneous ventilation to pre-relaxation values indicates complete recovery from neuromuscular blockade.', 'Prospective, with each individual acting as its own control.', 'Ten healthy adult female Beagle dogs weighing 6.2-9.4\\xa0kg.', 'Dogs were anesthetized with propofol, dexemedetomidine and isoflurane. Spontaneous ventilation was assessed by measuring end-tidal CO2 , expired tidal volume, peak inspiratory flow, respiratory rate and minute ventilation. Vecuronium 25\\xa0\u03bcg\\xa0kg(-1) IV was administered and neuromuscular block was evaluated by measuring the train-of-four (TOF) ratio with acceleromyography in the hind limb. During spontaneous recovery from neuromuscular block, the TOF ratio when each ventilatory variable returned to baseline was recorded.', 'This dose of vecuronium produced moderate neuromuscular block in all dogs, with TOF ratio values of 0-18% at maximal block. Expired tidal volume, peak inspiratory flow and minute ventilation returned to pre-relaxation values when the median TOF ratio was \u2264 20%. The median TOF ratio was 42% when the end-tidal CO2 returned to pre-relaxation values.",
            "output": [
                "Does recovery from neuromuscular block in dogs : restoration of spontaneous ventilation exclude residual blockade?"
            ]
        },
        {
            "id": "task847-71132ccf7ef0457c9c06bb36bbaf5393",
            "input": "To determine the effects of co-ingesting caffeine (CAF) and carbohydrate (CHO) on high-intensity intermittent sprints (HIS) performance and physiological responses.', 'Twelve active males underwent 4 interventions at least 7\\xa0days apart in a randomized, double-blind, placebo-controlled, balanced trial. A meal contained 65\\xa0% CHO was provided 2\\xa0h before the HIS test. Participants ingested the placebo (PLA) or CAF (6\\xa0mg\\xa0kg(-1) BW) 1\\xa0h before taking an HIS test, and ingested a PLA or CHO solution (0.8\\xa0g\\xa0kg(-1)\\xa0BW) before undergoing the testing protocol. The HIS protocol comprised ten sets of 5\\xa0\u00d7\\xa04-s sprints on a cycle ergometer with a 2-min recovery between each set.', 'There was no significant difference between peak power output and mean power output between trials (p\\xa0>\\xa00.05). Compared with PLA, CAF\\xa0+\\xa0CHO resulted in a 5.2\\xa0% reduction in total work, corresponding to a 24.7-25.7\\xa0% increase in fatigue at the end stage of the HIS. The administration of CAF\\xa0+\\xa0CHO supplementation also resulted in an 11.1\\xa0% increase in blood lactate, and elevated blood glucose concentrations throughout HIS testing compared with PLA (p\\xa0<\\xa00.05). Cortisol concentrations also increased with CAF\\xa0+\\xa0CHO intake compared with PLA; however, there was no significant effect of CAF\\xa0+\\xa0CHO supplementation on testosterone concentrations.",
            "output": [
                "Does co-ingestion of caffeine and carbohydrate after meal improve performance at high-intensity intermittent sprints with short recovery times?"
            ]
        },
        {
            "id": "task847-496dd7ad791d4bbeb5696e2a158a0126",
            "input": "This study investigated the isolated and combined effects of heat [temperate (22\\xa0\u00b0C/30\\xa0% rH) vs. hot (35\\xa0\u00b0C/40\\xa0% rH)] and hypoxia [sea level (FiO2 0.21) vs. moderate altitude (FiO2 0.15)] on exercise capacity and neuromuscular fatigue characteristics.', 'Eleven physically active subjects cycled to exhaustion at constant workload (66\\xa0% of the power output associated with their maximal oxygen uptake in temperate conditions) in four different environmental conditions [temperate/sea level (control), hot/sea level (hot), temperate/moderate altitude (hypoxia) and hot/moderate altitude (hot\\xa0+\\xa0hypoxia)]. Torque and electromyography (EMG) responses following electrical stimulation of the tibial nerve (plantar-flexion; soleus) were recorded before and 5\\xa0min after exercise.', 'Time to exhaustion was reduced (P\\xa0<\\xa00.05) in hot (-35\\xa0\u00b1\\xa015\\xa0%) or hypoxia (-36\\xa0\u00b1\\xa014\\xa0%) compared to control (61\\xa0\u00b1\\xa028\\xa0min), while hot\\xa0+\\xa0hypoxia (-51\\xa0\u00b1\\xa020\\xa0%) further compromised exercise capacity (P\\xa0<\\xa00.05). However, the effect of temperature or altitude on end-exercise core temperature (P\\xa0=\\xa00.089 and P\\xa0=\\xa00.070, respectively) and rating of perceived exertion (P\\xa0>\\xa00.05) did not reach significance. Maximal voluntary contraction torque, voluntary activation (twitch interpolation) and peak twitch torque decreased from pre- to post-exercise (-9\\xa0\u00b1\\xa01, -4\\xa0\u00b1\\xa01 and -6\\xa0\u00b1\\xa01\\xa0% all trials compounded, respectively; P\\xa0<\\xa00.05), with no effect of the temperature or altitude. M-wave amplitude and root mean square activity were reduced (P\\xa0<\\xa00.05) in hot compared to temperate conditions, while normalized maximal EMG activity did not change. Altitude had no effect on any measured parameters.",
            "output": [
                "Does combining heat stress and moderate hypoxia reduce cycling time to exhaustion without modifying neuromuscular fatigue characteristics?"
            ]
        },
        {
            "id": "task847-1258e9b0a7074946bae1dbab16ddec5c",
            "input": "The aim of the present study was to study patterns in the extended spectrum of the human hearing (0.125 to 20 kHz) in order to obtain reference thresholds. Then, we compare our values with existing results at extended high-frequencies (8 to 20 kHz) in an attempt to establish new standards for potential international adoption.', 'A prospective study in a group of otologically healthy subjects.', 'A total of 645 subjects aged between 5 and 90 years were recruited. Pure-tone thresholds were determined for conventional and extended high-frequencies.', 'There was an increase in the hearing thresholds as a function of frequency and age. For the 20 to 69 years old group, thresholds were lower in females than in males, especially at 12.5 and 16 kHz. Our threshold values are comparable to those presented in previous studies that used different instrumentation and populations.",
            "output": [
                "Do extended high-frequency ( 9-20 kHz ) audiometry reference thresholds in 645 healthy subjects?"
            ]
        },
        {
            "id": "task847-1e92e28ed44948e7b47173b339ecbfa4",
            "input": "FAAH degrades endocannabinoids and fatty acid amides. FAAH inhibition reduces micturition frequency and counteracts bladder overactivity in rats. We studied the effects of the peripherally active selective FAAH inhibitor URB937, and the CB1 and CB2 receptor antagonists rimonabant and SR144528, respectively, on single unit afferent activity of primary bladder afferents in rats.', 'Female Sprague Dawley\u00ae rats were anesthetized. Single unit afferent activity of A\u03b4 or C-fibers from the L6 dorsal roots was recorded during bladder filling before and after URB937 administration with or without rimonabant or SR144528. Drugs (1 mg/kg) were given intravenously. FAAH, CB1 and CB2 expression, and expression of the sensory marker CGRP in\\xa0the L6 dorsal root ganglion were compared by immunofluorescence.', 'A total of 102 single afferent fibers (48 A\u03b4 and 54 C-fibers) were isolated from 57 rats. URB937 decreased single unit afferent activity of C-fibers to a mean \u00b1 SEM of 78% \u00b1 9% and of A\u03b4-fibers to a mean of 67% \u00b1 7% while increasing bladder compliance to a mean of 116% \u00b1 3%. The effects of URB937 on single unit afferent activity and bladder compliance were counteracted by rimonabant or SR144528. Rimonabant increased single unit afferent activity of\\xa0each fiber type but SR144528 affected only A\u03b4-fiber activity. CGRP positive L6\\xa0dorsal root ganglion neurons showed strong FAAH, CB1 and CB2 staining.",
            "output": [
                "Does inhibition of peripheral FAAH depress activities of bladder mechanosensitive nerve fibers of the rat?"
            ]
        },
        {
            "id": "task847-a1b62b4b18f3468abbf9f769e44ac569",
            "input": "Data on serum soluble Klotho levels in chronic kidney disease are contradictory and even less is known after renal transplantation. Experimental studies demonstrated that recombinant human erythropoietin (rhEPO) treatment mitigates Klotho reduction caused by renal damage. Therefore, this study aimed to determine serum Klotho levels in a cohort of kidney transplant recipients (KTR) and to evaluate whether rhEPO treatment can modulate, in vivo and in vitro, soluble Klotho.', '117 KTR and 22 healthy subjects (HS) were enrolled. In 17 KTR, rhEPO was discontinued for 5 weeks and Klotho levels were compared to 34 propensity score-matched controls. Moreover, we evaluated Klotho mRNA expression and protein secretion in HK-2 tubular cells treated with cyclosporin A (CyA) and rhEPO, alone or in combination.', 'Serum Klotho levels in KTR were significantly higher than in HS (0.68 vs. 0.37, p = 0.002) and significantly associated with estimated glomerular filtration rate (r = -0.378, p = 0.003) and fibroblast growth factor 23 (r = -0.307, p < 0.0001). After 5 weeks of rhEPO discontinuation, treated KTR showed a sharper reduction of Klotho levels than controls (-0.56 vs. -0.11 ng/ml, p < 0.0001). In HK-2 cells CyA treatment induced a Klotho down-regulation that was mitigated by rhEPO pre-treatment. In the same experimental conditions, our results revealed that cells treated with CyA + rhEPO secreted higher soluble Klotho levels than those exposed to CyA or rhEPO alone.",
            "output": [
                "Are soluble Klotho levels in adult renal transplant recipients modulated by recombinant human erythropoietin?"
            ]
        },
        {
            "id": "task847-b14cc2abebc447d7b83ffdd2c78aac3d",
            "input": "Although falls in people with Parkinson's disease (PD) associate with dual tasking and freezing of gait (FoG), it is not known whether falls during dual tasking are due to FoG. This study investigated the effects of a cognitive task on the occurrence of falls and FoG when subjects with PD step in response to a postural perturbation.\", 'Ten subjects with PD and a history of FoG as well as 10 age-matched subjects without PD stepped in response to large, backward displacements of the support surface, with and without performing a fluency task of listing items in a category. Subjects with PD performed the task in the \"off\" and \"on\" dopaminergic medication states. We recorded the percentage of trials with FoG (a lack of step in response to the perturbation), foot-lift latencies, and trials with falls into a safety harness.', 'Dual tasking significantly increased the incidence of falls in people with PD, but subjects without PD did not fall in any condition. Dual tasking did not significantly increase trials without steps or foot-lift latencies. Falls were often coincident with a lack of step (FoG) in the single-task condition, but the increased falls with dual tasking occurred on trials with steps. Levodopa tended to decrease FoG and falls with or without dual tasking. However, medication did not significantly alter the effects of dual tasking on FoG or falls.",
            "output": [
                "Does dual tasking during postural stepping responses increase falls but not freezing in people with Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-9be7658e037d46eeb733d36e541756bf",
            "input": "Lieber-DeCarli diet has been used to induce obesity and non-alcoholic steatohepatitis (NASH). As scarce anatomical and clinical-related information on this diet model exists and being exercise an advised strategy to counteract metabolic diseases, we aimed to analyze the preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect of exercise on clinical/anatomical features of rats fed with Lieber-DeCarli diet.', 'In the beginning of the protocol, Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 20), standard-diet VPA (SVPA, n = 10), high-fat diet sedentary (HS, n = 20) and high-fat diet VPA (HVPA, n = 10) groups. After 9-weeks, half (n = 10) of SS and HS groups were engaged in an ET program (8 wks/5 d/wk/60 min/day). At this time, a blood sample was collected for biochemical analysis. At the end of protocol (17-weeks) anatomic measures were assessed. Heart, liver, femur and visceral fat were weighted and blood was collected again. Liver section was used for histopathological examination.', 'At 17-weeks, high-fat diet increased visceral adiposity (HS vs. SS), which was counteracted by both exercises. However, ET was the only intervention able to diminished obesity-related measures and the histological features of NASH. Moreover, blood analysis at 9 weeks showed that high-fat diet increased ALT, AST, cholesterol and HDL while VLDL and TG levels were decreased (HS vs. SS). Notably, although these parameters were counteracted after 9-weeks of VPA, they were transitory and not observed after 17-weeks.",
            "output": [
                "Does physical exercise antagonize clinical and anatomical features characterizing Lieber-DeCarli diet-induced obesity and related metabolic disorders?"
            ]
        },
        {
            "id": "task847-ea515ea95bdd4418988811879bb7541f",
            "input": "In a collaborative effort between the Missouri Department of Health, Area Agencies on Aging (AAA), Alzheimer Association, and academic researchers, we tested whether early dementia detection and comprehensive care consultations would improve health outcomes in care receivers (CRs) and their family caregivers (FCGs), therefore addressing an important public health concern.', 'A total of 244 community-dwelling older adults screened for early-stage dementia by the AAA field staff were referred to the Alzheimer Association and participated in Project Learn MORE (Missouri Outreach and Referral Expanded) (PLM) - a 2-year, nonrandomized multisite intervention consisting of comprehensive care consultations to improve coping skills. PLM participants were compared against 96 controls receiving the Alzheimer Association\\'s \"usual services\" between January 2011 and December 2012. We examined CR and FCG outcomes, including burden, care confidence, and mood, as effects of PLM, on delaying transitions in level of care.', \"CRs showed improved knowledge (P=0.002) and reduced depression (P=0.007), while FCGs demonstrated improved knowledge (P=0.003) and ability to identify sources of support for the CR (P=0.032) and for themselves (P=0.043). However, FCGs were more burdened after PLM (P=0.02), due to increased awareness of Alzheimer's disease. PLM delayed transitions in care (odds ratio [OR] 3.32, 95% confidence level [CI]: 1.25-8.83) with the number needed to treat =6.82.",
            "output": [
                "Do public-private partnerships improve health outcomes in individuals with early stage Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-241fe93a4fde423b85ee0f9b88399c2d",
            "input": "The aim of this study was to evaluate the effect of local injection of vasopressin on blood loss and secondary impact on complications during cesarean section in patients with placenta previa.', 'We retrospectively reviewed the medical records of all patients diagnosed with placenta previa admitted to our hospital. Two consecutive periods were compared. During period B, 59 patients underwent the local injection of a vasopressin solution (4 U in 20 mL of saline) into the placental implantation site after placental delivery. During period A, 50 patients underwent cesarean section without vasopressin injection, and were analyzed as a control group. The estimated blood loss was recorded, as were the complications during surgery. In addition, the expression of the vasopressin V1\u03b1 receptor in uterine smooth muscle was evaluated by immunohistochemistry.', 'The mean estimated blood loss was significantly lower in the vasopressin group than in the control group. There were no statistically significant differences with surgical complications. The vasopressin V1\u03b1 receptor was highly expressed in smooth muscle cells in the lower segment of the uterine body, whereas the immunoreactivity for the oxytocin receptor was faint in the lower segment.",
            "output": [
                "Does local injection of vasopressin reduce the blood loss during cesarean section in placenta previa?"
            ]
        },
        {
            "id": "task847-c6bff94e9fad4b6c925889f2aa0f9bfa",
            "input": "Kochia scoparia (Chenopodiaceae) has been reported to have anti-nociceptive, anti-inflammatory, anti-allergic, and anti-pruritic actions. This study investigated the anti-inflammatory effects of externally applied Kochia scoparia water extract (KSW) in 2,4-dinitrochlorobenzene (DNCB)-induced contact dermatitis mouse model.', 'To develop atopic dermatitis-like skin lesions, 100\u03bcL of 1% DNCB in acetone/olive oil (4:1) had been applied for three days on shaved dorsal skin. 1% KSW was topically applied to DNCB-induced mice. After KSW treatment, histological analysis was measured by hematoxylin eosin staining. The cytokine and pro-inflammatory expressions were examined using reverse transcription polymerase chain reaction and western blotting analysis.', 'Histological studies showed that hyperplasia of the epidermis and dermis in the KSW treated group was markedly decreased as compared with the DNCB group. The expression levels of pro-inflammatory cytokine such as IL-1\u03b2, and TNF-\u03b1 mRNA were significantly reduced by topical application of KSW, whereas these cytokines were increased in DNCB-induced dorsal skin. In addition, NF-\u03baB expression was inhibited by KSW treatment in DNCB-induced mice. Similarly, KSW treatment significantly suppressed the expression of several MAP kinases, including ERK1/2, p38, and JNK compared to their expression in DNCB-induced mice.",
            "output": [
                "Does topical application of Kochia scoparia inhibit the development of contact dermatitis in mice?"
            ]
        },
        {
            "id": "task847-41a04f446c7545599fd4fd61ead42a44",
            "input": "Huang-Lian-Jie-Du-Tang (HLJDT) is a classical heat-clearing and detoxicating formula of traditional Chinese medicine that is widely used to treat stroke. The present study was designed to investigate the effects of HLJDT preconditioning on neurons under oxygen and glucose deprivation (OGD) and rats subjected to middle cerebral artery occlusion (MCAO).', 'A stroke model of rats was obtained through MCAO. Following HLJDT preconditioning, the cerebral infarction volume, cerebral water content, and neurological deficient score were determined. Cerebral cortical neurons cultured in vitro were preconditioned with HLJDT and then subjected to OGD treatment. The release of lactate dehydrogenase (LDH) from neurons was detected. The levels of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) and PI3K/Akt signaling were analyzed by western blotting, and the levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the supernatant of the neurons and the plasma of MCAO rats were measured through a radioimmunological assay. The apoptosis and proliferation of neurons were analyzed by immunohistochemistry.', 'HLJDT preconditioning significantly reduced the cerebral infarction volume and cerebral water content and ameliorated the neurological deficient score of MCAO rats. In addition, HLJDT preconditioning protected neurons against OGD. Increased HIF-1\u03b1, EPO, and VEGF levels and the activation of PI3K/Akt signaling were observed as a result of HLJDT preconditioning. Furthermore, HLJDT preconditioning was found to inhibit ischemia-induced neuron apoptosis and to promote neuron proliferation under conditions of ischemia/reperfusion.",
            "output": [
                "Does preconditioning with the traditional Chinese medicine Huang-Lian-Jie-Du-Tang initiate HIF-1\u03b1-dependent neuroprotection against cerebral ischemia in rats?"
            ]
        },
        {
            "id": "task847-9c8627c0afea4f2cbf3d46071c8c0276",
            "input": "The aim of the study was to determine whether experimental manipulation of sense of control would change moderate drinkers' (N=106) task-specific motivational structure and explicit and implicit determinants of their urge to drink alcohol.\", \"The effects of various levels of information-enhancement and goal-setting on participants' performance on experimental tasks were assessed. Participants were randomly assigned to a high-sense-of-control, low-sense-of-control, or no-intervention group. Dependent measures were indices derived from a task-specific version of the Personal Concerns Inventory and the Shapiro Control Inventory, Alcohol Urge Questionnaire, and alcohol Stroop test.\", 'At baseline, there were no differences among the groups on any of the measures; however, post-experimentally, induced sense of control had led to increases in adaptive motivation and decreases in explicit and implicit measures of the urge to drink.",
            "output": [
                "Does information-enhancement and goal setting techniques for increasing adaptive motivation and decreasing urge to drink alcohol?"
            ]
        },
        {
            "id": "task847-9edb8af8983846bc8724ff3767aa9f75",
            "input": "Pulmonary embolism (PE) is common in patients with deep venous thrombosis (DVT). The outcome of DVT with concomitant symptomatic PE is worse than the outcome of isolated DVT. The risk factors for DVT and simultaneous asymptomatic PE have not been systematically studied yet.', 'To evaluate the frequency and risk factors for asymptomatic PE in patients with DVT.', 'In 155 consecutive patients with a first episode of DVT and no PE symptoms, a ventilation-perfusion lung scan was performed. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated and concentrations of D-dimer, high-sensitivity CRP (hsCRP), tissue plasminogen activator (t-PA) and troponin were measured. Laboratory tests for thrombophilia were performed.', 'Asymptomatic PE was present in 36% of patients. No differences in gender, age, BMI and WHR were found between the patients with and without PE. PE was more common in patients with proximal DVT than in those with distal DVT (42% vs. 17%, p<0.01), and in patients with unprovoked DVT compared to patients with provoked DVT (51% vs. 28%, p<0.01). The risk of silent PE was the highest in patients with unprovoked proximal DVT (OR, 6.9; 95% CI, 2.3-21.0). Patients with asymptomatic PE had significantly higher values of D-dimer, hsCRP, t-PA and troponin than patients with isolated DVT.",
            "output": [
                "Is unprovoked proximal venous thrombosis associated with an increased risk of asymptomatic pulmonary embolism?"
            ]
        },
        {
            "id": "task847-466d0dd7139f4766857b7596b5921c96",
            "input": "Selenium is an essential mineral for immunological function, performing crucial functions at the cellular level. This micronutrient has been determined to be frequently deficient in HIV infected patients, with correlations between reduced immunological function and greater susceptibility to opportunistic infections. Our aim was to evaluate the influence of time of exposure to antiretroviral therapy (ART) on the biochemical profile of selenium in HIV-infected patients.', 'We performed a cross-sectional study on 50 HIV-positive men with different quantitations of viral load and CD4+ T cells, who were either receiving or not receiving ART. Dual energy X-ray absorptiometry (DXA) to determine body composition, biochemical analysis of selenium and albumin, anthropometric measurements were performed. The subjects were divided into groups according to the use of ART or not: The Control Group (CG) was 10 treatment-na\u00efve volunteers, Group G < 2 was 20 volunteers on ART for less than 2 years, and Group G > 2 was 20 volunteers on ART for >2 years.', 'The body mass index showed that all subjects were of normal weight. The group with a longer time of exposure to ART (G > 2) had undetectable viremia and a higher CD4+ T cell count: 593.1 \u00b1 234.6 mm(3). Selenium values (\u03bcg/L) were 55.9 \u00b1 11.9 for CG, 52.1 \u00b1 10.5 for G < 2, and 66.9 \u00b1 20.8 for G > 2, with a significant difference between groups G < 2 and G > 2 (p < 0.05), and only G > 2 showed normal selenium values.",
            "output": [
                "Does a longer time of exposure to antiretroviral therapy improve selenium levels?"
            ]
        },
        {
            "id": "task847-954c600a59764943b1cfb28594436c0d",
            "input": "The aim of this study was to determine the effects of mesenchymal stem cell (MSC) application and the possible pathways of MSC's effects on tendon strength and healing after tendon repair.\", 'The study included 40 Wistar albino rats. Mesenchymal stem cells were obtained from the femurs and tibias of 6 rats. Achilles tendons of the remaining 34 rats were cut and repaired with open surgical procedures. Rats were divided into 2 groups. Percutaneous MSCs were applied to the study group (n=17) and physiological serum only was applied to the control group (n=17) at the 4th week. Rats were sacrificed using the cervical dislocation method under ether anesthesia at the 12th week and samples were analyzed by histological and immunohistochemical methods. For biomechanical analysis, a traction force was applied at 10 mm/min and load to failure was recorded for each specimen in Newtons.', 'Histologically, there was no significant difference between groups (p>0.05). In the immunohistochemical studies, MSCs were located more intensively at the repair zone. Apoptosis was minimally present in the study group and was clearly increased in the control group. Increase in tendon strength was significantly higher in the study group than in the control group at the 12th week (p<0.05).",
            "output": [
                "Does mesenchymal stem cell application improve tendon healing via anti-apoptotic effect ( Animal study )?"
            ]
        },
        {
            "id": "task847-831d4886a8044528b9d084420a5aeb31",
            "input": "A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs) with interleukins (IL-4, IL-5, and IL-10), transforming growth factor beta 1 (TGF-\u03b21), and interferon gamma (IFN-\u03b3) in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene.', 'A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions). Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-\u03b21, and IFN-\u03b3 in 103 patients and 100 healthy individuals was carried out.', 'An association analysis between 42 inhibitor (+) and 61 inhibitor (-) patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251). The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele.",
            "output": [
                "Is a Polymorphism in the IL-5 Gene Associated with Inhibitor Development in Severe Hemophilia A Patients?"
            ]
        },
        {
            "id": "task847-1eab073e4bbd4e20a1e839b218c1a5f3",
            "input": "Although neoadjuvant chemotherapy (NAC) for locally advanced breast cancer can improve operability and local disease control, there is a lack of reliable biomarkers that predict response to chemotherapy or long-term survival. Since expression of aldehyde dehydrogenase-1 (ALDH1) is associated with the stem-like properties of self-renewal and innate chemoresistance in breast cancer, we asked whether expression in serial tumor samples treated with NAC could identify women more likely to benefit from this therapy.', \"Women with locally advanced breast cancer were randomly assigned to receive four cycles of anthracycline-based chemotherapy, followed by four cycles of taxane therapy (Arm A), or the same regimen in reverse order (Arm B). Tumor specimens were collected at baseline, after four cycles, and then at surgical resection. ALDH1 expression was determined by immunohistochemistry and correlated with tumor response using Fisher's exact test while Kaplan-Meier method was used to calculate survival.\", 'A hundred and nineteen women were enrolled into the study. Fifty seven (48%) were randomized to Arm A and 62 (52%) to Arm B. Most of the women (90%) had ductal carcinoma and 10% had lobular carcinoma. Of these, 26 (22%) achieved a pathological complete response (pCR) after NAC. There was no correlation between baseline ALDH1 expression and tumor grade, stage, hormone receptor, human epidermal growth factor receptor 2 (HER2) status and Ki67 index. ALDH1 negativity at baseline was significantly associated with pCR (P\\u2009=\\u20090.004). The presence of ALDH1(+) cells in the residual tumor cells in non-responding women was strongly predictive of worse overall survival (P\\u2009=\\u20090.024). Moreover, serial analysis of specimens from non-responders showed a marked increase in tumor-specific ALDH1 expression (P\\u2009=\\u20090.028). Overall, there was no survival difference according to the chemotherapy sequence. However, poorly responding tumours from women receiving docetaxel chemotherapy showed an unexpected significant increase in ALDH1 expression.",
            "output": [
                "Do changes in aldehyde dehydrogenase-1 expression during neoadjuvant chemotherapy predict outcome in locally advanced breast cancer?"
            ]
        },
        {
            "id": "task847-5fa085aeebd34eaeba5786d0e33383a1",
            "input": "Acute lung injury (ALI) induced by excessive hyperoxia has been employed as a model of oxidative stress imitating acute respiratory distress syndrome. Under hyperoxic conditions, overloading quantities of reactive oxygen species (ROS) are generated in both lung epithelial and endothelial cells, leading to ALI. Some NADPH oxidase (NOX) family enzymes are responsible for hyperoxia-induced ROS generation in lung epithelial and endothelial cells. However, the molecular mechanisms of ROS production in type II alveolar epithelial cells (AECs) and ALI induced by hyperoxia are poorly understood.', 'In this study, we show that dual oxidase 2 (DUOX2) is a key NOX enzyme that affects hyperoxia-induced ROS production, particularly in type II AECs, leading to lung injury. In DUOX2 mutant mice (DUOX2(thyd/thyd)) or mice in which DUOX2 expression is knocked down in the lungs, hyperoxia-induced ALI was significantly lower than in wild-type (WT) mice. DUOX2 was mainly expressed in type II AECs, but not endothelial cells, and hyperoxia-induced ROS production was markedly reduced in primary type II AECs isolated from DUOX2(thyd/thyd) mice. Furthermore, DUOX2-generated ROS are responsible for caspase-mediated cell death, inducing ERK and JNK phophorylation in type II AECs.', 'To date, no role for DUOX2 has been defined in hyperoxia-mediated ALI despite it being a NOX homologue and major ROS source in lung epithelium.",
            "output": [
                "Is dual oxidase 2 in lung epithelia essential for hyperoxia-induced acute lung injury in mice?"
            ]
        },
        {
            "id": "task847-32e8892854594629b5481ecb6504253f",
            "input": "Pathogens dependent upon vectors for transmission to new hosts undergo environment specific changes in gene transcription dependent on whether they are replicating in the vector or the mammalian host. Differential gene transcription, especially of potential vaccine candidates, is of interest in Anaplasma marginale, the tick-borne causative agent of bovine anaplasmosis.', 'RNA-seq technology allowed a comprehensive analysis of the transcriptional status of A. marginale genes in two conditions: bovine host blood and tick derived cell culture, a model for the tick vector. Quantitative PCR was used to assess transcription of a set of genes in A. marginale infected tick midguts and salivary glands at two time points during the transmission cycle.', 'Genes belonging to fourteen pathways or component groups were found to be differentially transcribed in A. marginale in the bovine host versus the tick vector. One of the most significantly altered groups was composed of surface proteins. Of the 56 genes included in the surface protein group, eight were up regulated and 26 were down regulated. The down regulated surface protein encoding genes include several that are well studied due to their immunogenicity and function. Quantitative PCR of a set of genes demonstrated that transcription in tick cell culture most closely approximates transcription in salivary glands of recently infected ticks.",
            "output": [
                "Does global transcriptional analysis reveal surface remodeling of Anaplasma marginale in the tick vector?"
            ]
        },
        {
            "id": "task847-2e45237094094722901c57f36da123c5",
            "input": "To study the effect of Cleistocalyx nervosum extract (CE) on diethylnitrosamine (DEN) and phenobarbital (PB) induced oxidative stress in early stages of rat hepatocarcinogenesis.', 'Male Wistar rats were divided into 4 groups, with Group 1 as a negative control and Group 2 was a positive control receiving DEN injections once a week and PB in drinking water for 6 weeks. Two weeks before DEN initiation and PB treatment, Groups 3 and 4, were fed with 500 and 1000 mg/kg of CEs, respectively, for 8 weeks.', 'A number of GST-P-positive foci, preneoplastic lesions, in the liver were markedly increased in carcinogen administered rats, but was comparatively decreased in rats treated with 1000 mg/kg of CE. The CE reduced malondialdehyde in serum and in the livers of rats treated with DEN and PB. Moreover, CE significantly increased the activities of glutathione peroxidase and catalase in rat liver.",
            "output": [
                "Does cleistocalyx nervosum extract ameliorate chemical-induced oxidative stress in early stages of rat hepatocarcinogenesis?"
            ]
        },
        {
            "id": "task847-ae1b126b818f4a9ca8ef8061b21a1105",
            "input": "The modification of the Model for End-Stage Liver Disease (MELD) scoring system (Refit MELD) and the modification of MELD-Na (Refit MELDNa), which optimized the MELD coefficients, were published in 2011. We aimed to validate the superiority of the Refit MELDNa over the Refit MELD for the prediction of 3-month mortality in Korean patients with cirrhosis and ascites.', 'We reviewed the medical records of patients admitted with hepatic cirrhosis and ascites to the Konkuk University Hospital between January 2006 and December 2011. The Refit MELD and Refit MELDNa were compared using the predictive value of the 3-month mortality, as assessed by the Child-Pugh score.', 'In total, 530 patients were enrolled, 87 of whom died within 3 months. Alcohol was the most common etiology of their cirrhosis (n=271, 51.1%), and the most common cause of death was variceal bleeding (n=20, 23%). The areas under the receiver operating curve (AUROCs) for the Child-Pugh, Refit MELD, and Refit MELDNa scores were 0.754, 0.791, and 0.764 respectively; the corresponding values when the analysis was performed only in patients with persistent ascites (n=115) were 0.725, 0.804, and 0.796, respectively. The significant difference found among the Child-Pugh, Refit MELD, and Refit MELDNa scores was between the Child-Pugh score and Refit MELD in patients with persistent ascites (P=0.039).",
            "output": [
                "Is the Refit model for end-stage liver disease-Na a better predictor of mortality than the Refit model for end-stage liver disease in patients with cirrhosis and ascites?"
            ]
        },
        {
            "id": "task847-f9d88d642ca3420baee0c6c6fcee39c6",
            "input": "Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking sub-clinical hyperthyroidism (SHT). The aim of the present study was to retrospectively evaluate changes in several electrocardiographic indices in euthyroid subjects with diabetes who, after starting metformin treatment, developed a low serum TSH as compared to patients with SHT resulting from an underlying thyroid disease or TSH suppressive treatment with L-thyroxine.', 'Heart rate, P wave duration, P wave dispersion, QTmax, QTmin and QT-dispersion were assessed in 23 patients with diabetes treated with metformin before and after 6 months of TSH-suppression and in 31 control patients with SHT.', 'No significant changes in electrocardiographic parameters were observed from baseline to the TSH-suppression measurement. A significant difference in P wave duration (102.9 \u00b1 7.4 vs. 92.1 \u00b1 5.8 ms, p<0.001), P wave dispersion (13.1 \u00b1 3.4 vs. 7.1 \u00b1 3.5 ms, p<0.001), QTmax (399 \u00b1 18 vs. 388 \u00b1 16 ms, p=0.024), QTmin (341 \u00b1 14 vs. 350 \u00b1 17 ms, p=0.038) and QT dispersion (49.9 \u00b1 9.6 vs. 30.9 \u00b1 9.2 ms, p<0.001) were observed between the control group with SHT and the group of diabetic patients with low serum levels of TSH.",
            "output": [
                "Is metformin-induced thyrotropin suppression associated with cardiac effects?"
            ]
        },
        {
            "id": "task847-019ad28de07f4b65a91307b06a818102",
            "input": "To investigate the adverse effect of intravitreal injection of normal saline (NS) and phosphate buffered saline (PBS) in mouse eyes.', 'NS or PBS was injected intravitreally into C57BL/6J mouse eyes. Retinal lesions were monitored by fundus imaging, spectral-domain optical coherence tomography (SD-OCT), and histological investigations. Retinal immune gene expression was determined by real-time polymerase chain reaction (PCR). The toxic effect of NS and PBS or retinal protein from NS- or PBS-injected eyes on retinal pigment epithelium (RPE) was tested in B6-RPE-07 mouse RPE cell cultures.', 'Intravitreal injection of NS dose-dependently induced localized retinal lesion in mice. Histological investigations revealed multiple vacuoles in photoreceptor outer segments and RPE cells. The lesions recovered over time and by 3 weeks post injection the majority of lesions vanished in eyes receiving 1 \u03bcl NS. Inflammatory genes, including ",
            "output": [
                "Does intravitreal Injection of Normal Saline induce Retinal Degeneration in the C57BL/6J Mouse?"
            ]
        },
        {
            "id": "task847-134cf5b7b01a46819c83bf333f6cfb7a",
            "input": "Cyclovirobuxinum D (CVB-D), an alkaloid isolated from the Chinese medicinal plant Buxus microphylla, has been found to be effective to treat cardiac insufficiency, arrhythmias and coronary heart disease. In the present study, we investigated the effects of CVB-D on the inflammatory responses in lipopolysaccharide (LPS)-stimulated murine macrophages in vitro and the underlying mechanisms.', 'Murine macrophage cell line RAW264.7 cells were incubated in the presence of LPS (0.1 \u03bcg/mL) for 24 h. The cell viability was measured using MTT assay. The release of NO and cytokines were detected using the Griess test and ELISA, respectively. The mRNA and protein levels were determined using RT-PCR and Western blot, respectively. Reporter gene assays were used to analyze the transcriptional activity of NF-\u03baB.', 'Treatment of RAW264.7 cells with CVB-D (25-300 \u03bcmol/L) did not affect the cell viability. Pretreatment with CVB-D (50, 100 and 200 \u03bcmol/L) concentration-dependently decreased NO release and iNOS expression in LPS-treated RAW264.7 cells (its IC50 value in inhibition of NO production was 144 \u03bcmol/L). CVB-D also concentration-dependently inhibited the secretion and mRNA expression of IL-1\u03b2 and IL-6 in LPS-treated RAW264.7 cells. Furthermore, CVB-D remarkably inhibited the phosphorylation of STAT1 and STAT3, as well as JAK2 in LPS-treated RAW264.7 cells, but did not affect the activation of NF-\u03baB and MAPKs pathways. Pretreatment with the JAK2 specific inhibitor AG490 (30 \u03bcmol/L) produced similar effects on NO release and iNOS expression in LPS-treated RAW264.7 cells.",
            "output": [
                "Does cyclovirobuxinum D suppress lipopolysaccharide-induced inflammatory responses in murine macrophages in vitro by blocking JAK-STAT signaling pathway?"
            ]
        },
        {
            "id": "task847-1fc7ac0c71bb4516ad7ad55a063fbb8a",
            "input": "Wnt signalling pathways regulate proliferation, motility and survival in a variety of human cell types. Dickkopf 1 (DKK1) gene codes for a secreted Wnt inhibitory factor. It functions as tumour suppressor gene in breast cancer and as a pro-apoptotic factor in glioma cells. In this study, we aimed to demonstrate whether the different expression of DKK1 in human glioma-derived cells is dependent on microenvironmental factors like hypoxia and regulated by the intercellular crosstalk with bone-marrow-derived mesenchymal stem cells (bmMSCs).', 'Glioma cell line U87-MG, three cell lines from human glioblastoma grade IV (glioma-derived mesenchymal stem cells) and three bmMSCs were selected for the experiment. The expression of DKK1 in cell lines under normoxic/hypoxic environment or co-culture condition was measured using real-time PCR and enzyme-linked immunoadsorbent assay. The effect of DKK1 on cell migration and proliferation was evaluated by in vitro wound healing assays and sulphorhodamine assays, respectively.', 'Glioma-derived cells U87-MG displayed lower DKK1 expression compared with bmMSCs. Hypoxia led to an overexpression of DKK1 in bmMSCs and U87-MG when compared to normoxic environment, whereas co-culture of U87-MG with bmMSCs induced the expression of DKK1 in both cell lines. Exogenous recombinant DKK1 inhibited cell migration on all cell lines, but did not have a significant effect on cell proliferation of bmMSCs and glioma cell lines.",
            "output": [
                "Is the expression of Wnt-inhibitor DKK1 ( Dickkopf 1 ) determined by intercellular crosstalk and hypoxia in human malignant gliomas?"
            ]
        },
        {
            "id": "task847-7cb9c1fa914143e889376a1ca30539b5",
            "input": "In clinical practice, veterinarians often depend on owner-reported signs to assess the clinical course of horses with recurrent airway obstruction (RAO).', 'To test whether owner-reported information on frequency of coughing and observation of nasal discharge are associated with clinical, cytological and bronchoprovocation findings in RAO-affected horses in nonstandardised field conditions.', 'Cross-sectional study comparing healthy and RAO-affected horses.', \"Twenty-eight healthy and 34 RAO-affected Swiss Warmblood horses were grouped according to owner-reported 'coughing frequency' and 'nasal discharge'. Differences between these groups were examined using clinical examination, blood gas analyses, endoscopic mucus scores, cytology of tracheobronchial secretion and bronchoalveolar lavage fluid, and airway hyperresponsiveness determined by plethysmography with histamine bronchoprovocation.\", 'Frequently coughing horses differed most markedly from healthy control animals. Histamine bronchoprovocation-derived parameters were significantly different between the healthy control group and all RAO groups. Mucus grades and tracheobronchial secretion and bronchoalveolar lavage fluid neutrophil percentages had particularly high variability, with overlap of findings between groups. Owner satisfaction with the clinical status of the horse was high, even in severely affected horses.",
            "output": [
                "Are owner-reported coughing and nasal discharge associated with clinical findings , arterial oxygen tension , mucus score and bronchoprovocation in horses with recurrent airway obstruction in a field setting?"
            ]
        },
        {
            "id": "task847-f4b7c32b608b4cf09071741d83431e64",
            "input": "Use of enriched environment (EE) housing has been shown to promote recovery from cerebral ischaemic injury but the underlying mechanisms of their beneficial effects remains unclear. Here we examined whether the beneficial effects of EE housing on ischaemia-induced neurodegeneration and cognitive impairment are associated with increased insulin-like growth factor-1 (IGF-1) signalling in the hippocampus.', 'Forty-two adult male Wistar rats were included in the study and received either ischaemia or sham surgery. Rats in each group were further randomized to either: EE or standard laboratory cage housing (control). Rats were placed in their assigned housing condition immediately after recovery from anaesthesia. Behavioural testing in the cued learning and discrimination learning tasks were conducted 2\\u2009weeks after ischaemia. Rats were euthanized after behavioural testing and the hippocampus was analysed for IGF-1 level, IGF-1 receptor (IGF-1R) activation, protein kinase B (Akt) pathway activation, neurone loss and caspase 3 expression.', 'Our data showed that EE housing: (1) mitigated ischaemia-induced neuronal loss; (2) attenuated ischaemia-induced increase in caspase 3 immunoreactivity in the hippocampus; (3) ameliorated ischaemia-induced cognitive impairments; and (4) increased IGF-1R activation and signalling through the Akt pathway after ischaemic injury.",
            "output": [
                "Are neuroprotective effects of enriched environment housing after transient global cerebral ischaemia associated with the upregulation of insulin-like growth factor-1 signalling?"
            ]
        },
        {
            "id": "task847-225fc598596b41b2bf74ed7657a8e07b",
            "input": "Glioblastoma multiforme (GBM) is a highly malignant human brain neoplasm with limited therapeutic options. GBMs display a deregulated apoptotic pathway with high levels of the antiapoptotic Bcl-2 family of proteins and overt activity of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Therefore, combined interference of the PI3K pathway and the Bcl-2 family of proteins is a reasonable therapeutic strategy. ABT-263 (Navitoclax), an orally available small-molecule Bcl-2 inhibitor, and GDC-0941, a PI3K inhibitor, were used to treat established glioblastoma and glioblastoma neurosphere cells, alone or in combination. Although GDC-0941 alone had a modest effect on cell viability, treatment with ABT-263 displayed a marked reduction of cell viability and induction of apoptotic cell death. Moreover, combinatorial therapy using ABT-263 and GDC-0941 showed an enhanced effect, with a further decrease in cellular viability. Furthermore, combination treatment abrogated the ability of stem cell-like glioma cells to form neurospheres. ABT-263 and GDC-0941, in combination, resulted in a consistent and significant increase of Annexin V positive cells and loss of mitochondrial membrane potential compared with either monotherapy. The combination treatment led to enhanced cleavage of both initiator and effector caspases. Mechanistically, GDC-0941 depleted pAKT (Serine 473) levels and suppressed Mcl-1 protein levels, lowering the threshold for the cytotoxic actions of ABT-263. GDC-0941 decreased Mcl-1 in a posttranslational manner and significantly decreased the half-life of Mcl-1 protein. Ectopic expression of human Mcl-1 mitigated apoptotic cell death induced by the drug combination. Furthermore, GDC-0941 modulated the phosphorylation status of BAD, thereby further enhancing ABT-263-mediated cell death.",
            "output": [
                "Does pI3K and Bcl-2 inhibition prime glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD?"
            ]
        },
        {
            "id": "task847-19747584c6274b7b9d8786a198482205",
            "input": "We tested the hypothesis that harm avoidance, a trait associated with behavioral inhibition, is associated with the rate of change in parkinsonism in older adults.', \"At baseline harm avoidance was assessed with a standard self-report instrument in 969 older people without dementia participating in the Rush Memory and Aging Project, a longitudinal community-based cohort study. Parkinsonism was assessed annually with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale (mUPDRS).\", 'Average follow-up was 5 years. A linear mixed-effects model controlling for age, sex and education showed that for an average participant (female, 80 years old at baseline, with 14 years of education and a harm avoidance score of 10), the overall severity of parkinsonism increased by about 0.05 unit/ year (Estimate, 0.054, S.E., 0.007, p <0.001) and that the level of harm avoidance was associated with the progression of parkinsonism (Estimate, 0.004, S.E., 0.001, p <0.001). Thus, for an average participant, every 6 point (~1 SD) increase in harm avoidance score at baseline, the rate of progression of parkinsonism increased about 50% compared to an individual with an average harm avoidance score. This amount of change in parkinsonism over the course of the study was associated with about a 5% increased risk of death. The association between harm avoidance and progression of parkinsonism persisted when controlling for cognitive function, depressive symptoms, loneliness, neuroticism, late-life cognitive, social and physical activities and chronic health conditions.",
            "output": [
                "Is harm avoidance associated with progression of parkinsonism in community-dwelling older adults : a prospective cohort study?"
            ]
        },
        {
            "id": "task847-981b0603529e4e3fa75b3bb8e5fa1d60",
            "input": "Clinical manifestations of enterovirus 71 (EV71) range from herpangina, hand-foot-and-mouth disease (HFMD), to severe neurological complications. Unlike the situation of switching genotypes seen in EV71 outbreaks during 1998-2008 in Taiwan, genotype B5 was responsible for two large outbreaks in 2008 and 2012, respectively. In China, by contrast, EV71 often persists as a single genotype in the population and causes frequent outbreaks. To investigate genetic changes in viral evolution, complete EV71 genome sequences were used to analyze the intra-genotypic evolution pattern in Taiwan, China, and the Netherlands.', \"Genotype B5 was predominant in Taiwan's 2008 outbreak and was re-emergent in 2012. EV71 strains from both outbreaks were phylogenetically segregated into two lineages containing fourteen non-synonymous substitutions predominantly in the non-structural protein coding region. In China, genotype C4 was first seen in 1998 and caused the latest large outbreak in 2008. Unlike shifting genotypes in Taiwan, genotype C4 persisted with progressive drift through time. A majority of non-synonymous mutations occurred in residues located in the non-structural coding region, showing annual increases. Interestingly, genotype B1/B2 in the Netherlands showed another stepwise evolution with dramatic EV71 activity increase in 1986. Phylogeny of the VP1 coding region in 1971-1986 exhibited similar lineage turnover with genotype C4 in China; however, phylogeny of the 3D-encoding region indicated separate lineage appearing after 1983, suggesting that the 3D-encoding region of genotype B2 was derived from an unidentified ancestor that contributed to intra-genotypic evolution in the Netherlands.",
            "output": [
                "Do mutations in the non-structural protein region contribute to intra-genotypic evolution of enterovirus 71?"
            ]
        },
        {
            "id": "task847-ac557f5dc7fa4b0b836c3c980d875629",
            "input": "Gastric Helicobacter pylori (H. pylori) infection and colorectal polyps are more prevalent in African Americans than in the general population. We aimed to investigate whether gastric H. pylori infection is associated with colorectal polyps in African Americans.', 'Medical records of African Americans, 40 years and older (n = 1256) who underwent bidirectional gastrointestinal endoscopy on the same day were reviewed. H. pylori status was assessed by immunohistochemistry on gastric specimens. Colorectal polyps were confirmed by histological examination of colorectal biopsies. A subset of serum samples from healthy and polyp-bearing patients (n = 163) were analyzed by ELISA for anti-H. pylori and anti-CagA antibodies. The crude and adjusted effect of H. pylori on the risk of colorectal adenoma and polyp were computed by logistic regression models.', \"The prevalence of colorectal polyps and adenomas were 456 (36%) and 300 (24%) respectively. Colorectal polyps were more prevalent in gastric H. pylori infected than non-infected subjects [43% vs. 34%; Odds Ratio (OR) (95% CI): 1.5 (1.2-1.9), P = 0.001]. Patients with H. pylori-associated chronic active gastritis were at high risk to have adenomas [Unadjusted OR (95% CI): 1.3 (1.0-1.8); P = 0.04]. There was no difference in histopathology, size, or location of polyps with respect to H. pylori status. Gastric H. pylori infection, age, male gender and high risk clinical presentations were independent risk factors for colorectal polyps. Serological testing also revealed a higher prevalence of H. pylori and its toxin Cag-A in polyp patients vs. non polyp patients' sera, although in a non-statistically significant manner.",
            "output": [
                "Does gastric Helicobacter pylori infection associate with an increased risk of colorectal polyps in African Americans?"
            ]
        },
        {
            "id": "task847-ebabae5f32d04cf09ec607be00a31ccf",
            "input": "In patients with moderate-to-severe psoriasis, health-related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity.', 'To evaluate the role of pruritus (itch) in mediating the relationship between improvements in disease severity and HRQOL.', 'Data from a phase 2 clinical trial, in which 142 patients with moderate-to-severe plaque psoriasis received ixekizumab or placebo, were used for this posthoc analysis. Relationships between improvement in Psoriasis Area and Severity Index (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment, work and school, daily activities, leisure, and personal relationships) from baseline to week 16 were determined. Multiple hierarchical linear regressions and Sobel tests were conducted to evaluate the results.', 'Improvement in PASI was highly correlated with pruritus improvement and improvements in DLQI total and domain scores at week 16 (P\\xa0<\\xa00\u00b701). Multiple hierarchical linear regression analyses showed a statistically significant (P\\xa0<\\xa00\u00b701) association between improvement in pruritus and improvement in DLQI total score and each of the six DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated that pruritus had a significant mediation effect (P\\xa0<\\xa00\u00b705) on the association of PASI improvement with improvement in DLQI total score and all domains except the personal relationships score.",
            "output": [
                "Is itching a significant problem and a mediator between disease severity and quality of life for patients with psoriasis : results from a randomized controlled trial?"
            ]
        },
        {
            "id": "task847-acf8eb7f8f1a4ff4a8077f607b408450",
            "input": "Esophageal squamous cell carcinoma (ESCC) is one of the most malignant diseases and the five year survival rate remains less than 10%. RASSF10 is a newly identified member of the Ras-association family, but the regulation and the function of RASSF10 in ESCC remain unclear. Research methodologies such as methylation specific PCR (MSP), semi-quantitative RT-PCR, immunohistochemistry, Sodium bisulfite sequencing, and colony formation assay were utilized in this investigation. Loss of RASSF10 expression was found in KYSE150 cells and reduced expression was found in KYSE70 and KYSE180 cells. Expression of RASSF10 was found in KYSE140, KYSE450, KYSE510, TE1, TE3, and TE8 cell lines. Complete methylation was found in KYSE30 and KYSE150 cells, partial methylation was found in KYSE70, KYSE180, KYSE510, and TE1, and unmethylation was found in KYSE140, KYSE450, TE3, and TE8. Re-expression or increased expression was induced by 5-Aza-dC treatment. RASSF10 was methylated in 44.3% primary esophageal squamous cell carcinoma. RASSF10 inhibits cell proliferation and induces G2/M phase arrest in esophageal cancer cells.",
            "output": [
                "Does epigenetic silencing of RASSF10 promote tumor growth in esophageal squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-b8c636a37f0b4e708ca9d1a2657f4202",
            "input": "Development of novel strategies in the treatment of advanced thyroid cancer are needed. Our laboratory has previously identified a role for nuclear factor \u03baB (NF-\u03baB) signaling in human thyroid cancer cell growth, survival, and invasion.', 'Our goal was to establish the role of NF-\u03baB signaling on thyroid cancer growth and metastases in vivo and to begin to dissect mechanisms regulating this effect.', 'We examined tumor formation of five thyroid cancer cell lines in an in vivo model of thyroid cancer and observed tumor establishment in two of the cell lines (8505C and BCPAP).', 'Inhibition of NF-\u03baB signaling by overexpression of a dominant-negative I\u03baB\u03b1 (mI\u03baB\u03b1) significantly inhibited thyroid tumor growth in tumors derived from both cell lines. Further studies in an experimental metastasis model demonstrated that NF-\u03baB inhibition impaired growth of tumor metastasis and prolonged mouse survival. Proliferation (mitotic index) was decreased in 8505C tumors, but not in BCPAP tumors, while in vitro angiogenesis and in vivo tumor vascularity were significantly inhibited by mIkB\u03b1 only in the BCPAP cells. Cytokine antibody array analysis demonstrated that IL-8 secretion was blocked by mI\u03baB\u03b1 expression. Interestingly, basal NF-\u03baB activity and IL-8 levels were significantly higher in the two tumorigenic cell lines compared with the nontumorigenic lines. Furthermore, IL-8 transcript levels were elevated in high-risk human tumors, suggesting that NF-\u03baB and IL-8 are associated with more aggressive tumor behavior.",
            "output": [
                "Is nuclear factor \u03baB-dependent regulation of angiogenesis , and metastasis in an in vivo model of thyroid cancer associated with secreted interleukin-8?"
            ]
        },
        {
            "id": "task847-c7f828f0fe484789bc3e065c473210e6",
            "input": "Prolonged re-exposure to a fear-eliciting cue in the absence of an aversive event extinguishes the fear response to the cue, and has been clinically used as an exposure therapy. Arc (also known as Arg3.1) is implicated in synaptic and experience-dependent plasticity. Arc is regulated by the transcription factor cAMP response element binding protein, which is upregulated with and necessary for fear extinction. Because Arc expression is also activated with fear extinction, we hypothesized that Arc expression is required for fear extinction.', 'Extinction training increased the proportion of Arc-labeled cells in the basolateral amygdala (BLA). Arc was transcribed during latter part of extinction training, which is possibly associated with fear extinction, as well as former part of extinction training. Intra-BLA infusions of Arc antisense oligodeoxynucleotide (ODN) before extinction training impaired long-term but not short-term extinction memory. Intra-BLA infusions of Arc antisense ODN 3\\xa0h after extinction training had no effect on fear extinction.",
            "output": [
                "Does fear extinction require Arc/Arg3.1 expression in the basolateral amygdala?"
            ]
        },
        {
            "id": "task847-6cd87406ffa2411886fa25b836804c0f",
            "input": "Serum response factor (SRF) is a widely expressed transcription factor involved in multiple regulatory programs. It is believed that SRF can toggle between disparate programs of gene expression through association with different cofactors. However, the direct evidence as to how these factors function on a genome-wide level is still lacking.', 'In the present study, I explored the functions of SRF and its representative cofactors, megakaryoblastic leukemia 1/2 (MKL1/2) and ETS-domain protein 4 (ELK4), during fungal infection challenge in macrophages. The knockdown study, combined with gene expression array analysis, revealed that MKL1/2 regulated SRF-dependent genes were related to actin cytoskeleton organization, while ELK4 regulated SRF-dependent genes were related to external stimulus responses. Subsequent chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) suggested that many of these regulations were mediated directly in cis.",
            "output": [
                "Do mKL1/2 and ELK4 co-regulate distinct serum response factor ( SRF ) transcription programs in macrophages?"
            ]
        },
        {
            "id": "task847-e477328edfa243ffb9e6acdf3920b929",
            "input": "Infection with Leishmania parasites causes mainly cutaneous lesions at the site of the sand fly bite. Inflammatory metastatic forms have been reported with Leishmania species such as L. braziliensis, guyanensis and aethiopica. Little is known about the factors underlying such exacerbated clinical presentations. Leishmania RNA virus (LRV) is mainly found within South American Leishmania braziliensis and guyanensis. In a mouse model of L. guyanensis infection, its presence is responsible for an hyper-inflammatory response driven by the recognition of the viral dsRNA genome by the host Toll-like Receptor 3 leading to an exacerbation of the disease. In one instance, LRV was reported outside of South America, namely in the L. major ASKH strain from Turkmenistan, suggesting that LRV appeared before the divergence of Leishmania subgenera. LRV presence inside Leishmania parasites could be one of the factors implicated in disease severity, providing rationale for LRV screening in L. aethiopica.', 'A new LRV member was identified in four L. aethiopica strains (LRV-Lae). Three LRV-Lae genomes were sequenced and compared to L. guyanensis LRV1 and L. major LRV2. LRV-Lae more closely resembled LRV2. Despite their similar genomic organization, a notable difference was observed in the region where the capsid protein and viral polymerase open reading frames overlap, with a unique -1 situation in LRV-Lae. In vitro infection of murine macrophages showed that LRV-Lae induced a TLR3-dependent inflammatory response as previously observed for LRV1.",
            "output": [
                "Do leishmania aethiopica field isolates bearing an endosymbiontic dsRNA virus induce pro-inflammatory cytokine response?"
            ]
        },
        {
            "id": "task847-8d6609c162554cf7a6b9938397527494",
            "input": "Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown.', 'In this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control.', 'The acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected.",
            "output": [
                "Does cromolyn ameliorate acute and chronic injury in a rat lung transplant model?"
            ]
        },
        {
            "id": "task847-30e01402705e43dd9e288e1228a6e10a",
            "input": "Sprague and Tatum (1942) introduced the concepts of general combining ability (GCA) and specific combining ability (SCA) to evaluate the breeding parents and F1 hybrid performance, respectively. Since then, the GCA was widely used in cross breeding for elite parent selection. However, the molecular basis of GCA remains to unknown.', 'We studied the transcriptomes of three varieties and three\\xa0F1 hybrids using RNA-Sequencing. Transcriptome sequence analysis revealed that the transcriptome profiles of the F1s were similar to the positive GCA-effect parent. Moreover, the expression levels of most differentially expressed genes (DEGs) were equal to the parent with a positive GCA effect. Analysis of the gene expression patterns of gibberellic acid (GA) and flowering time pathways that determine plant height and flowering time in rice validated the preferential transcriptome expression of the parents with positive GCA effect. Furthermore, H3K36me3 modification bias in the Pseudo-Response Regulators (PRR) gene family was observed in the positive GCA effect parents and demonstrated that the phenotype and transcriptome bias in the positive GCA effect parents have been epigenetically regulated by either global modification or specific signaling pathways in rice.",
            "output": [
                "Is the phenotypic predisposition of the parent in F1 hybrid correlated with transcriptome preference of the positive general combining ability parent?"
            ]
        },
        {
            "id": "task847-3d54f597a3a846aaa2da5a5c230c840f",
            "input": "To compare the performance of the bias-adjusted meta-analysis to the conventional meta-analysis assessing seasonal influenza vaccine effectiveness among community-dwelling elderly aged 60 years and older.', 'Systematic literature search revealed 14 cohort studies that met inclusion and exclusion criteria. Laboratory-confirmed influenza, influenza-like illness, hospitalization from influenza and/or pneumonia, and all-cause mortality were study outcomes. Potential biases were identified using bias checklists. The magnitude and uncertainty of biases were assessed by expert opinion. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using random effects model.', 'After incorporating biases, overall effect estimates regressed slightly toward no effect, with the largest relative difference between conventional and bias-adjusted ORs for laboratory-confirmed influenza (OR, 0.18; 95% CI: 0.01, 3.00 vs. OR, 0.23; 95% CI: 0.03, 2.04). In most of the studies, CIs widened reflecting uncertainties about the biases. The between-study heterogeneity reduced considerably with the largest reduction for all-cause mortality (I(2) = 4%, P = 0.39 vs. I(2) = 91%, P < 0.01).",
            "output": [
                "Does after adjusting for bias in meta-analysis seasonal influenza vaccine remain effective in community-dwelling elderly?"
            ]
        },
        {
            "id": "task847-3175a04b3bea4a66a138e33c50c586ab",
            "input": "Treatment-resistant depression (TRD) is a pervasive and difficult to treat condition for which deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) is an emerging therapeutic option. However, neuropsychological safety data for this novel treatment have only been published for a small number of subjects. Moreover, little is known regarding the neuropsychological profile present in TRD patients at baseline, prior to initiation of DBS therapy. This report describes the neuropsychological effects of TRD and acute and chronic DBS of the SCCwm in patients with unipolar and bipolar TRD.', 'Patients with TRD (N = 17) were compared to a healthy control group (N = 15) on subtests from the Cambridge Neuropsychological Test Automated Battery and the Stroop Task. Patients were then tested again at subsequent time points of 1 and 6 months following the initiation of chronic DBS of the SCCwm.', 'Patients with TRD showed similar levels of performance to healthy controls on most neuropsychological measures, with the exception that the TRD group had slower processing speed. Patients with bipolar TRD, relative to those with unipolar TRD, obtained lower scores on measures of executive function and memory only at baseline. With acute and chronic SCCwm DBS, neuropsychological function improved in multiple domains including processing speed and executive function (planning, set shifting, response inhibition), and memory remained stable.",
            "output": [
                "Do neuropsychological function before and after subcallosal cingulate deep brain stimulation in patients with treatment-resistant depression?"
            ]
        },
        {
            "id": "task847-b61df47443ab47f5932f1e1701ff44fd",
            "input": "This paper tests the contribution of the toll-like receptors, TLR4 in particular, in the initiation and maintenance of paclitaxel-related chemotherapy-induced peripheral neuropathy. TLR4 and its immediate downstream signaling molecules-myeloid differentiation primary response gene 88 (MyD88) and toll/interleukin 1 receptor domain-containing adapter-inducing interferon-\u03b2 (TRIF)-were found to be increased in the dorsal root ganglion (DRG) using Western blot by day 7 of paclitaxel treatment. The behavioral phenotype, the increase of both TLR4 and MyD88, was blocked by cotreatment with the TLR4 antagonist lipopolysaccharide-Rhodobacter sphaeroides during chemotherapy. A similar, but less robust, behavioral effect was observed using intrathecal treatment of MyD88 homodimerization inhibitory peptide. DRG levels of TLR4 and MyD88 reduced over the next 2 weeks, whereas these levels remained increased in spinal cord through day 21 following chemotherapy. Immunohistochemical analysis revealed TLR4 expression in both calcitonin gene-related peptide-positive and isolectin B4-positive small DRG neurons. MyD88 was only found in calcitonin gene-related peptide-positive neurons, and TRIF was found in both calcitonin gene-related peptide-positive and isolectin B4-positive small DRG neurons as well as in medium- and large-size DRG neurons. In the spinal cord, TLR4 was only found colocalized to astrocytes but not with either microglia or neurons. Intrathecal treatment with the TLR4 antagonist lipopolysaccharide-R. sphaeroides transiently reversed preestablished chemotherapy-induced peripheral neuropathy mechanical hypersensitivity. These results strongly implicate TLR4 signaling in the DRG and the spinal cord in the induction and maintenance of paclitaxel-related chemotherapy-induced peripheral neuropathy.",
            "output": [
                "Does toll-like receptor 4 signaling contribute to Paclitaxel-induced peripheral neuropathy?"
            ]
        },
        {
            "id": "task847-936389b766bf44d6b0838e10dee0d33d",
            "input": "Probiotics can prevent pathological bacterial translocation in cirrhosis by modulating intestinal microbiota and improving gut barrier and immune disturbances. To evaluate the effect of probiotic VSL#3 on bacterial translocation, intestinal microbiota, gut barrier and inflammatory response in rats with experimental cirrhosis.', 'Forty-six Sprague-Dawley rats with CCl4 -induced cirrhosis were randomized into two groups: VSL#3 group (n = 22) that received VSL#3 in drinking water, and water group (n = 24) that received water only. Treatment began at week 6 of cirrhosis induction and continued until laparotomy, performed 1 week after development of ascites or at week 20. A control group included 11 healthy rats. At this study end, we evaluated bacterial translocation, intestinal flora, intestinal barrier (ileal claudin-2 and 4, \u03b2-defensin-1, occludin and malondialdehyde as index of oxidative damage) and serum cytokines.', 'Mortality during this study was similar in the VSL#3 group (10/22, 45%) and the water group (10/24, 42%) (P = 1). The incidence of bacterial translocation was 1/12 (8%) in the VSL#3 group, 7/14 (50%) in the water group (P = 0.03 vs. VSL#3 group) and 0/11 in the control group (P = 0.008 vs. water group). The concentration of ileal and caecal enterobacteria and enterococci was similar in the two groups of cirrhotic rats. The ileal occludin concentration was higher and ileal malondialdehyde and serum levels of TNF-\u03b1 were lower in the VSL#3 group than in the water group (P < 0.05).",
            "output": [
                "Does vSL # 3 probiotic treatment decrease bacterial translocation in rats with carbon tetrachloride-induced cirrhosis?"
            ]
        },
        {
            "id": "task847-9a653f2d34374501af83b33c43097dff",
            "input": "We investigated whether aprepitant, a neurokinin-1 antagonist, could decrease chemotherapy-induced nausea and vomiting (CINV) following cisplatin, when a conventional anti-emetic regimen had failed.', 'This was a prospective study (April 2011-April 2012) of patients with lung cancer, treated with cisplatin at the Beijing Cancer Hospital, and initially receiving granisetron, dexamethasone, and metoclopramide as anti-emetics. If patients experienced vomiting of grade \u22652 and required rescue anti-emetic medications during the first cycle, oral aprepitant was added in subsequent cycles (day 1: 125 mg; days 2-3: 80 mg once daily). Acute (day 1) and delayed (days 2-5) nausea and vomiting, use of rescue medications, and occurrence of adverse reactions were monitored after the start of chemotherapy.', 'Twenty-five of 132 patients (18.9 %) were administered aprepitant for secondary prophylaxis against emesis during the second cycle of chemotherapy. The incidences of acute and delayed nausea were 52 and 100 % in the first cycle, but 8 and 72 % in the second cycle. The incidences of acute and delayed vomiting were 20 and 100 % in the first cycle, but 0 and 36 % in the second cycle. No patients required rescue medications or intravenous rehydration during the second cycle. Aprepitant was not associated with additional adverse events.",
            "output": [
                "Does addition of aprepitant improve protection against cisplatin-induced emesis when a conventional anti-emetic regimen fails?"
            ]
        },
        {
            "id": "task847-6880a7041d0f4872a9d80badfd3672ec",
            "input": "Angiogenesis and vascular remodelling are crucial events in tissue repair mechanisms promoted by cell transplantation. Current evidence underscores the importance of the soluble factors secreted by stem cells in tissue regeneration. In the present study we investigated the effects of paracrine factors derived from cultured endothelial progenitor cells (EPC) on rat brain endothelial cell properties and addressed the signaling pathways involved.', 'Endothelial cells derived from rat brain (rBCEC4) were incubated with EPC-derived conditioned medium (EPC-CM). The angiogenic response of rBCEC4 to EPC-CM was assessed as effect on cell number, migration and tubular network formation. In addition, we have compared the outcome of the in vitro experiments with the effects on capillary sprouting from rat aortic rings. The specific PI3K/AKT inhibitor LY294002 and the MEK/ERK inhibitor PD98059 were used to study the involvement of these two signaling pathways in the transduction of the angiogenic effects of EPC-CM.', 'Viable cell number, migration and tubule network formation were significantly augmented upon incubation with EPC-CM. Similar findings were observed for aortic ring outgrowth with significantly longer sprouts. The EPC-CM-induced activities were significantly reduced by the blockage of the PI3K/AKT and MEK/ERK signaling pathways. Similarly to the outcome of the rBCEC4 experiments, inhibition of the PI3K/AKT and MEK/ERK pathways significantly interfered with capillary sprouting induced by EPC-CM.",
            "output": [
                "Does the secretome of endothelial progenitor cells promote brain endothelial cell activity through PI3-kinase and MAP-kinase?"
            ]
        },
        {
            "id": "task847-7650078d84584f528914c0cd50241b2a",
            "input": "Osteosarcoma is the most common primary bone malignancy and accounts for more than half of primary skeletal malignancies in children and young adults. Although vascular endothelial growth factor (VEGF) expression in osteosarcoma has been associated with poor outcome, its role in the pathogenesis of osteosarcoma remains controversial. Here, VEGF and VEGFR1 expression in both human and murine osteosarcoma cells associated with increasing malignant potential. Autocrine VEGF/VEGFR1 signaling resulted in constitutive activation of VEGFR1 in highly aggressive osteosarcoma cells. In addition, survival and proliferation of highly aggressive osteosarcoma cells was dependent on autocrine VEGF/R1 signaling in vitro. The effect of VEGFR1 expression on in vivo tumor growth and angiogenesis was evaluated by immunoselecting subpopulations of osteosarcoma cells that express high or low levels of VEGFR1. Cell enriched for high VEGFR1 expression showed increased VEGF production, tumor growth, tumor angiogenesis, and osteolysis in vivo. In addition, it was demonstrated that VEGF and VEGFR1 are coexpressed by a subset of tumor cells in human osteosarcoma, similar to what was observed in the murine osteosarcoma cells. These results suggest that autocrine VEGF/VEGFR1 signaling in a subpopulation of tumor cells plays a pivotal role in osteosarcoma progression.",
            "output": [
                "Does autocrine VEGF/VEGFR1 signaling in a subpopulation of cells associate with aggressive osteosarcoma?"
            ]
        },
        {
            "id": "task847-3626b7887cff4b818597acf7b2bfdb33",
            "input": "Semaphorins are guidance proteins implicated in several processes such as angiogenesis, organogenesis, cell migration, and cytokine release. Experimental studies showed that semaphorin-3a (SEMA3A) administration induces transient massive proteinuria, podocyte foot process effacement and endothelial cell damage in healthy animals. While SEMA3A signaling has been demonstrated to be mechanistically involved in experimental diabetic glomerulopathy and in acute kidney injury, to date its role in human chronic kidney disease (CKD) has not been investigated.', 'To test the hypothesis that SEMA3A may play a role in human CKD, we performed a cross-sectional, nested, case-control study on 151 matched hypertensive patients with and without CKD. SEMA3A was quantified in the urine (USEMA) by ELISA. Glomerular filtration rate was estimated (eGFR) by the CKD-EPI formula and albuminuria was measured as albumin-to-creatinine ratio (ACR).', 'USEMA levels were positively correlated with urine ACR (p = 0.001) and serum creatinine (p < 0.001). USEMA was higher in patients with both components of renal damage as compared to those with only one and those with normal renal function (p < 0.007 and <0.001, respectively). The presence of increased USEMA levels (i.e. top quartile) entailed a fourfold higher risk of combined renal damage (p < 0.001) and an almost twofold higher risk of macroalbuminuria (p = 0.005) or of reduced eGFR, even adjusting for confounding factors (p = 0.002).",
            "output": [
                "Is increased urine semaphorin-3A associated with renal damage in hypertensive patients with chronic kidney disease : a nested case-control study?"
            ]
        },
        {
            "id": "task847-59bc3086e4d24817856f42d78b6b0015",
            "input": "In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation.', \"Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNF-\u03b1-stimulated endothelial cells. Nuclear factor kappa B (NF-\u03baB) reporter gene assays confirmed that MOF decrease the activity of NF-\u03baB. Strong inter-individual variability in the leukocytes' DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found.",
            "output": [
                "Do dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state?"
            ]
        },
        {
            "id": "task847-d45c319a806a4788b0a2501aacbaf9f0",
            "input": "The B cell chemoattractant chemokine ligand 13 (CXCL13) is emerging as a new biochemical marker in RA. This study was undertaken to dissect the relationship between CXCL13 expression levels in the synovium and clinico-pathological variables relevant to RA pathogenesis and outcome.', 'Synovial tissues from 71 RA patients were evaluated by immunohistochemistry. Thirty paired samples were used for comparative gene expression analysis by quantitative real-time PCR. CXCL13 levels were analysed in relation to cellular, molecular and clinical features of inflammation, lymphocyte activation and joint damage.', 'In patients with early disease (<12 months duration), CXCL13 expression correlated significantly with synovial markers of local disease activity and systemic inflammation. Such correlation was less evident in established RA. Notably, the association with lymphocyte infiltration and with expression of B/T cell-related activation and proliferation genes, such as activation-induced cytidine deaminase, IFN-\u03b3 and IL-2, remained highly significant independent of disease duration and local disease activity. Patients featuring the highest levels of CXCL13 were more frequently ACPA positive and IgG ACPA titres were increased in the high CXCL13 expression group. Furthermore, the frequency of erosive disease on radiographs was significantly higher in the upper tertile of CXCL13 expression (P = 0.01 with adjustment for disease duration and ACPA). Accordingly, synovial CXCL13 and the local receptor activator of nuclear factor \u03baB ligand (RANKL)/osteoprotegerin (OPG) ratio significantly co-varied (\u03c1 = 0.52, P < 0.01), independent of the level of local inflammation.",
            "output": [
                "Are high expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium a marker of severe disease?"
            ]
        },
        {
            "id": "task847-c628bc1721de44c4a3a60db6714c0c1b",
            "input": "Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment.', 'Three hundred fifty-one male CCS were included. Median age at diagnosis was 5.9 years (0-17.8) and median age at follow-up 25.6 years (18.0-45.8). Total and non-SHBG-bound testosterone, sex hormone-binding globulin, inhibin B, and follicle-stimulating hormone (FSH) were studied. Potential determinants were BMI, waist circumference, waist-hip ratio, and body composition measures (dual energy X-ray absorptiometry).', 'Non-SHBG-bound testosterone was significantly decreased in survivors with BMI \u2265 30 kg/m(2) (adjusted mean 9.1 nmol/L vs. 10.2 nmol/L, P = 0.015), high fat percentage (10.0 vs. 11.2, P = 0.004), and high waist circumference (>102 cm) (9.0 vs. 11.0, P = 0.020). Survivors with high fat percentage (\u226525%) had significantly lower inhibin B/FSH ratios (inhibin B/FSH ratio: \u03b2 -34%, P = 0.041).",
            "output": [
                "Does obesity independently influence gonadal function in very long-term adult male survivors of childhood cancer?"
            ]
        },
        {
            "id": "task847-7695604726a84286af80b1e6fbbe220e",
            "input": "Ginsenoside Rg1, the major effective component of ginseng, possesses a variety of pharmacologic activities. The objective of this study was to investigate the effects of Rg1 on liver ischemia-reperfusion (IR) injury and explore its potential mechanisms.', 'Liver warm IR injury was achieved by occluding the portal vein and hepatic artery for 1 h followed by 6-h reperfusion. Eighteen mice were equally randomized into three groups: sham group, IR group, and IR plus Rg1 group (n = 6 mice per group). Mice received an intravenous dose of 20 mg/kg Rg1 or an equivalent volume of saline before ischemic insult. Liver samples and serum were collected for analyses. Serum aminotransferase, histopathology, and apoptosis were determined. Cytokines were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The phosphorylation of nuclear factor kappa B (NF-\u03baB) p65 was assessed by Western blotting. In addition, the effect of Rg1 in a simulated IR model in vitro was also investigated. Rg1 (100 ug/mL and 500 ug/mL) was administered 1 h before hypoxia insult, and then apoptosis was measured after 12-h reperfusion.', 'Liver IR injury led to a dramatic increase in aminopherase activity, apoptosis and necrosis of hepatocytes, and production of proinflammatory cytokines. Pretreatment with Rg1 protected mice from IR-induced liver injury. Treatment with a high-dose Rg1 (500 ug/mL) significantly suppressed apoptosis compared with a lower dose or control (both P < 0.001). Phosphorylation of NF-\u03baB p65 was increased significantly in IR group, and administration with Rg1 suppressed the level of phosphorylation.",
            "output": [
                "Does ginsenoside Rg1 protect mouse liver against ischemia-reperfusion injury through anti-inflammatory and anti-apoptosis properties?"
            ]
        },
        {
            "id": "task847-1f5f222d76554a70a3187c6b57339605",
            "input": "Congenital cytomegalovirus (cCMV) infection can result in poor outcomes including cerebral palsy (CP). The aim of this study was to describe the incidence and comorbidities of CP reported to the Australian Cerebral Palsy Register (ACPR) as attributed to cCMV infection.', 'This was a retrospective population-based study. Cases were drawn from Australian state CP registers with population level ascertainment, 1993 to 2003 (n=2265; 56.4% males, Gross Motor Function Classification System [GMFCS] ratings available for Victorian cases only: 70% GMFCS levels I to III and 30% GMFCS levels IV to V). Clinical data were extracted and cases with cCMV reported as a known cause were compared with cases where cCMV was not reported.', 'Children with cCMV (n=34; 12 males, 22 females; mean [SD] gestational age, 36.4 wk [4.4], range 24-41 wk) accounted for 1.5% of CP cases; 2.9 per 100,000 live births, (95% confidence intervals 1.9-3.9). When compared with CP cases where cCMV was not reported, proportionally, more CP cases with cCMV were born to younger mothers (p<0.001), were female (64% vs 43%, p=0.014), had spastic quadriplegia (73% vs 21%, p<0.001), required wheeled mobility i.e. GMFCS IV or V (78% vs 28%, p<0.001), had epilepsy (70% vs 30%, p<0.001), deafness (40% vs 2%, p<0.001), functional blindness (20% vs 5%, p<0.001), and severe communication impairment (71% vs 25%, p<0.001).",
            "output": [
                "Is congenital cytomegalovirus associated with severe forms of cerebral palsy and female sex in a retrospective population-based study?"
            ]
        },
        {
            "id": "task847-80779d7bc61946f981b97a967d377a4c",
            "input": "Transcription factors are critical in regulating lens development. The AP-2 family of transcription factors functions in differentiation, cell growth and apoptosis, and in lens and eye development. AP-2\u03b1, in particular, is important in early lens development, and when conditionally deleted at the placode stage defective separation of the lens vesicle from the surface ectoderm results. AP-2\u03b1's role during later stages of lens development is unknown. To address this, the MLR10-Cre transgene was used to delete AP-2\u03b1 from the lens epithelium beginning at embryonic day (E) 10.5.\", 'The loss of AP-2\u03b1 after lens vesicle separation resulted in morphological defects beginning at E18.5. By P4, a small highly vacuolated lens with a multilayered epithelium was evident in the MLR10-AP-2\u03b1 mutants. Epithelial cells appeared elongated and expressed fiber cell specific \u03b2B1 and \u03b3-crystallins. Epithelial cell polarity and lens cell adhesion was disrupted and accompanied by the misexpression of ZO-1, N-Cadherin, and \u03b2-catenin. Cell death was observed in the mutant lens epithelium between postnatal day (P) 14 and P30, and correlated with altered arrangements of cells within the epithelium.",
            "output": [
                "Is aP-2\u03b1 required after lens vesicle formation to maintain lens integrity?"
            ]
        },
        {
            "id": "task847-a0ac3c066b29489d918911d8836f5580",
            "input": "Exercise at 50-60\\xa0% of peak oxygen consumption (VO2 peak) stimulates maximal fat oxidation rates. Despite a lower estimated work performed; high-intensity intermittent exercise (HIIE) training produces greater fat mass reductions when compared with workload-matched continuous (CON) steady state exercise. No metabolic basis has been documented nor mechanisms offered to explain this anomaly. This study investigated the physiological and metabolic responses of two different workload-matched exercise protocols.', 'On separate occasions and at least 1\\xa0week apart, eight apparently healthy males cycled for 30\\xa0min at either 50\\xa0% VO2 peak (CON) or performed repeated 20\\xa0s bouts of supramaximal exercise at 150\\xa0%VO2 peak separated by 40\\xa0s rest (HIIE).', 'The average heart rate, oxygen consumption, plasma glycerol and free fatty acid concentrations were not different during exercise and recovery between the trials. Plasma lactate and hypoxanthine (Hx) concentrations were elevated and urinary excretion rates of Hx and uric acid were greater following HIIE as compared to CON (P\\xa0<\\xa00.05).",
            "output": [
                "Does high-intensity intermittent cycling increase purine loss compared with workload-matched continuous moderate intensity cycling?"
            ]
        },
        {
            "id": "task847-41c723b9369441e5b450fba1068a691a",
            "input": "Little information exists about how cognitive impairment in multiple sclerosis (MS) patients impacts on their caregivers' health-related quality of life (HRQoL).\", \"The objective of this paper is to examine the extent to which cognitive impairment in MS patients contributes to caregivers' HRQoL.\", 'A total of 63 MS patients, 63 caregivers and 59 matched controls were recruited. Patients and controls underwent a neuropsychological assessment, including tests of working memory, speed of information processing, executive function, and verbal fluency. HRQoL of the caregivers was assessed by CAREQOL-MS. In logistic regression models, we adjusted for the effects of confounding variables. In these models, the dependent variable was the CAREQOL-MS (higher median of CAREQOL-MS (worse HRQoL) vs. lower median of CAREQOL-MS (better HRQoL) (reference)), and the independent variable was the impairment on each neuropsychological test vs. its integrity (reference).', 'Cognitive impairment in MS patients was significantly associated with worse caregiver HRQoL (adjusted odds ratio (OR) = 3.10, 95% confidence interval (CI) = 1.07-11.55, p = 0.04). In secondary analyses in which each neuropsychological test was entered in the analyses separately, only Symbol Digit Modalities Test (a measurement of information processing speed) impairment (OR = 4.22, 95%, CI = 1.16-14.53, p = 0.03) was significantly associated with worse caregiver HRQoL.",
            "output": [
                "Does cognitive impairment in patients with multiple sclerosis predict worse caregiver 's health-related quality of life?"
            ]
        },
        {
            "id": "task847-bad5f40836e74ced990edb467c734ddd",
            "input": "To investigate the potential effects of berberine on renal interstitial fibrosis (RIF) of obstructed kidneys in a unilateral ureteral obstruction (UUO) rat model.', \"Forty-eight rats were randomly divided into three groups: sham-operated, vehicle-treated UUO, and berberine-treated UUO. Rats were gavaged with berberine (200\\u2009mg/kg per day) or vehicle. Eight randomly chosen rats in each group were kiled and specimens were collected at day 14 after UUO. Physiological parameters and histological changes were assessed, RIF was evaluated using Masson's trichrome and Sirius red staining, oxidative stress and inflammation markers were determined, transforming growth factor \u03b21 (TGF-\u03b21), phosphorylated Smad3 (pSmad3) and \u03b1-smooth muscle actin (\u03b1-SMA) were measured using immunohistochemistry or western blotting analysis. The obstruction was relieved at day 14 by percutaneous nephrostomy in the remaining UUO rats. The resistive index of left kidneys was undertaken by coloured Doppler flow imaging at day 14 before nephrostomy and day 7 after the relief.\", 'Berberine treatment significantly attenuated RIF induced by UUO. The UUO-induced reduction in kidney superoxide dismutase and catalase activities increased, whereas elevated kidney malondialdehyde level markedly decreased. Berberine treatment significantly ameliorated UUO-induced inflammation, and decreased TGF-\u03b21, pSmad3 and \u03b1-SMA expression of UUO kidneys. Moreover, berberine treatment significantly suppressed the increase of resistive index compared with UUO group at day 14 after UUO as well as day 7 after the relief of obstruction.",
            "output": [
                "Does berberine ameliorate renal interstitial fibrosis induced by unilateral ureteral obstruction in rats?"
            ]
        },
        {
            "id": "task847-bf41ef5700f14af89d6737a300ac7940",
            "input": "Evidence has accumulated indicating that microglia within the spinal cord play a critical role in morphine tolerance. The present study investigated the effects and possible mechanisms of 5' adenosine monophosphate-activated protein kinase (AMPK) activator resveratrol and AICAR to inhibit microglial activation and to limit the decrease in antinociceptive effects of morphine.\", 'The microglial cell line BV-2 was used. Cytokine expression was measured using quantitative polymerase chain reaction. Cell signalling was assayed by Western blot and immunohistochemistry. The antinociception and morphine tolerance were assessed in CD-1 mice using the hot plate and tail-flick tests.', '(1) Morphine induces robust BV-2 cell activation, as evidenced by increased p38 mitogen-activated protein kinase phosphorylation, nuclear factor-\u03baB translocation and mRNA expression of pro-inflammatory cytokines [including interleukin-1\u03b2 (IL-1\u03b2), IL-6 and tumour necrosis factor-\u03b1], inducible nitric oxide synthase and Toll-like receptor-4, and these changes are inhibited by resveratrol. (2) Resveratrol activates AMPK to suppress morphine-induced BV-2 cell activation. AICAR, another AMPK activator, can mimic the effects of resveratrol, whereas compound C, an AMPK inhibitor, reverses the inhibitory effects of resveratrol treatment. (3) Systemic or spinal administration of resveratrol with morphine significantly blocks microglial activation in the spinal cord and then attenuates the development of acute and chronic morphine tolerance in both male and female mice.",
            "output": [
                "Does resveratrol reduce morphine tolerance by inhibiting microglial activation via AMPK signalling?"
            ]
        },
        {
            "id": "task847-cc77966a80a74e698ae7f2fda70737f7",
            "input": "To analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1.', 'The study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed.', \"HCV mono-infected patients, with lower grading score (G<2) and higher HCV viral load (>600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman's \u03c1\\u200a=\\u200a0.586, p\\u200a=\\u200a0.000001) and miR-122 (Spearman's \u03c1\\u200a=\\u200a0.270, p\\u200a=\\u200a0.014059).",
            "output": [
                "Does hepatic HMOX1 expression positively correlate with Bach-1 and miR-122 in patients with HCV mono and HIV/HCV coinfection?"
            ]
        },
        {
            "id": "task847-f4112cb02f744c438d542aed0ee6585f",
            "input": "Blood oxygenation level-dependent (BOLD)-weighted and vessel-encoded arterial spin labeling (VE-ASL) MRI provide complementary information and can be used in sequence to gauge hemodynamic contributions to cerebrovascular reactivity. Here, cerebrovascular reactivity is assessed using dual echo VE-ASL MRI to understand how VE labeling preparations influence BOLD and ASL contrast in flow-limited and healthy perfusion territories.', 'Patients (n\\u2009=\\u200912; age\\u2009=\\u200955 +/- 14 years; 6F/6M) presenting with ischemic steno-occlusive cerebrovascular disease underwent 3.0T angiographic imaging, T1 -weighted structural, and planning-free dual echo hypercarbic hyperoxic (i.e., carbogen) VE-ASL MRI. Vasculopathy extent, timecourses, and cerebrovascular reactivity (signal change and Z-statistic) for different VE-ASL images were contrasted across flow territories and Bonferroni-corrected P-values reported.', 'BOLD cerebrovascular reactivity (i.e., long-TE VE-ASL) Z-statistics were similarly sensitive to asymmetric disease (P\\u2009\u2264\\u20090.002) regardless of labeling scenario. Cerebral blood flow reactivity correlated significantly with BOLD reactivity (Z-statistic). However, BOLD signal changes did not differ significantly between labeling scenarios (P\\u2009>\\u20090.003) or across territories (P\\u2009>\\u20090.002), indicating BOLD signal changes in response to carbogen offer low sensitivity to lateralizing disease.",
            "output": [
                "Do dual echo vessel-encoded ASL for simultaneous BOLD and CBF reactivity assessment in patients with ischemic cerebrovascular disease?"
            ]
        },
        {
            "id": "task847-1709b0e8d3a54f0d907377039f1915e0",
            "input": "To compare the safety and success of a retrograde approach using a microcatheter vs. a sheath in the treatment of superficial femoral artery (SFA) chronic total occlusions (CTOs).', 'From April 2007 to December 2012, 188 consecutive patients underwent EVT for 229 de novo SFA CTOs using the retrograde approach in 68 patients (35 men; mean age 72 years). This cohort was divided into cases performed with a 4-F or 6-F sheath (n=28, 36 limbs) and those with a 2.1-F microcatheter (n=35, 49 limbs). The primary outcomes were mean time to hemostasis and number of intra- and postoperative puncture site complications, as well as the success of popliteal artery puncture, lesion crossing, and reperfusion.', 'There were no significant differences between two groups in baseline characteristics. PA puncture was successful in all limbs, and the success in crossing the lesion with the wire was not significantly different (91.9% in the sheath group vs. 89.8% in the microcatheter group). Mean time to hemostasis was 8.9\u00b18.8 minutes in the microcatheter group vs. 47.7\u00b113 minutes in the sheath group (p<0.0001). There was a significant difference in intraoperative and postoperative complications (22.2% in the sheath group vs. 2.0% in the microcatheter group, p=0.002).",
            "output": [
                "Is a sheathless retrograde approach via the popliteal artery useful and safe for treating chronic total occlusions in the superficial femoral artery?"
            ]
        },
        {
            "id": "task847-04a73a5e786d4380882ab8594c2f2c68",
            "input": "To evaluate the relevance of systematic screening for neonatal metabolic acidosis at birth as part of perinatal audit.', 'For every baby, born in Ziekenhuis Oost Limburg, Genk Belgium between 1/1/2010 and 31/12/2010, cord blood was analysed to diagnose metabolic acidosis, defined as arterial or venous pH \u2264 7.05 or 7.17 respectively, in association with base excess of \u2264 -10\\u2008mmol/L. Three observers identified indicators for suboptimal peripartal care with likely contribution to metabolic acidosis. In a multidisciplinary consensus meeting, these indicators were classified into 5 categories : (a) fetal monitoring error (b) labour management error, (c) instrumental vaginal delivery for fetal distress within 2\\u2008h of second stage, (d) non-obstetric medical complications, (e) preterm births or accidental cases at term.', 'In a total of 2117 neonates, there were 11 intra-uterine, 1 intrapartum and 3 early neonatal deaths, bringing early perinatal mortality rate at 7.1\u2030. Metabolic acidosis was identified in 23 (1.1%) babies, of which 21 (91.3%) left hospital in good clinical condition. Two babies (0.9\u2030), born in category c, had chronic neurologic symptoms.",
            "output": [
                "Do identification of neonatal near miss by systematic screening for metabolic acidosis at birth?"
            ]
        },
        {
            "id": "task847-e66cdc68582e4da2973a0043ca1916f3",
            "input": "We sought to determine the association between low caregiver health literacy and child emergency department (ED) use, both the number and urgency of ED visits.', 'This year long cross-sectional study utilized the Newest Vital Sign questionnaire to measure the health literacy of caregivers accompanying children to a pediatric ED. Prior ED visits were extracted from a regional database. ED visit urgency was classified by resources utilized during the index ED visit. Regression analyses were used to model 2 outcomes-prior ED visits and ED visit urgency-stratified by chronic illness. Analyses were weighted by triage level.', 'Overall, 503 caregivers completed the study; 55% demonstrated low health literacy. Children of caregivers with low health literacy had more prior ED visits (adjusted incidence rate ratio 1.5; 95% confidence interval 1.2, 1.8) and increased odds of a nonurgent index ED visit (adjusted odds ratio 2.4; 95% confidence interval 1.3, 4.4). Among children without chronic illness, low caregiver health literacy was associated with an increased proportion of nonurgent index ED visits (48% vs. 22%; adjusted odds ratio 3.2; 1.8, 5.7).",
            "output": [
                "Is low caregiver health literacy associated with higher pediatric emergency department use and nonurgent visits?"
            ]
        },
        {
            "id": "task847-3cef6ddb0dc8468b8d86c6a57149650e",
            "input": "Ischemia-reperfusion injury (IRI) after lung transplantation remains a significant cause of morbidity and mortality. Lung IRI induces nitric oxide synthesis (iNOS) and reactive nitrogen species, decreasing nitric oxide bioavailability. We hypothesized that ischemia-induced iNOS intensifies with reperfusion and contributes to IRI-induced pulmonary arterial regulatory dysfunction, which may lead to early graft failure and cause pulmonary edema. The aim of this study was to determine whether ischemia-reperfusion alters inducible and endothelial nitric oxide synthase expression, potentially affecting pulmonary perfusion. We further evaluated the role of iNOS in post-transplantation pulmonary arterial disorder.', 'We randomized 32 Sprague-Dawley rats into two groups. The control group was given a sham operation whilst the experimental group received orthotropic lung transplants with a modified three-cuff technique. Changes in lung iNOS, and endothelial nitric oxide synthase expression were measured after lung transplantation by enzyme-linked immunosorbent assay (ELISA). Vasoconstriction in response to exogenous phenylephrine and vasodilation in response to exogenous acetylcholine of pulmonary arterial rings were measured in vitro as a measure of vascular dysfunction. To elucidate the roles of iNOS in regulating vascular function, an iNOS activity inhibitor (N6-(1-iminoethyl)-L-lysine, L-NIL) was used to treat isolated arterial rings. In order to test whether iNOS inhibition has a therapeutic effect, we further used L-NIL to pre-treat transplanted lungs and then measured post-transplantation arterial responses.', 'Lung transplantation caused upregulation of iNOS expression. This was also accompanied by suppression of both vasoconstriction and vasodilation of arterial rings from transplanted lungs. Removal of endothelium did not interfere with the contraction of pulmonary arterial rings from transplanted lungs. In contrast, iNOS inhibition rescued the vasoconstriction response to exogenous phenylephrine of pulmonary arterial rings from transplanted lungs. In addition, lung transplantation led to suppression of PaO2/FiO2 ratio, increased intrapulmonary shunt (Q s/Q t), and increase of lung wet to dry ratio (W/D), malondialdehyde and myeloperoxidase levels, all of which were reversed upon iNOS inhibition. Furthermore, inhibition of iNOS significantly rescued vascular function and alleviated edema and inflammatory cell infiltration in the transplanted lung.",
            "output": [
                "Does inducible nitric oxide synthase inhibition reverse pulmonary arterial dysfunction in lung transplantation?"
            ]
        },
        {
            "id": "task847-c7355a7055464fe7b8974705bcedc38b",
            "input": "Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients.', 'The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917.', 'Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG).",
            "output": [
                "Do iFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection?"
            ]
        },
        {
            "id": "task847-712b71fa8fc9423986c728552a4fb09e",
            "input": "The deficiency of glutathione (GSH) has been linked to several diseases. The study investigated the role of GSH as a protective factor against hyperglycemia-mediated injury in VL-17A cells treated with 50 mM glucose.', 'The cell viability and different oxidative stress parameters including glyoxalase I activity were measured.', 'GSH supplementation with 2 mM N-acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) increased the viability, GSH level and the GSH-dependent glyoxalase I activity in 50 mM glucose-treated VL-17A cells. Further, pretreatment of 50 mM glucose-treated VL-17A cells with NAC or UDCA decreased oxidative stress (levels of reactive oxygen species and protein carbonylation), apoptosis (caspase 3 activity and annexin V-propidium iodide positive cells) and glutathionylated protein formation, a measure of oxidative stress. GSH depletion with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) potentiated the decrease in viability, glyoxalase I activity and increase in oxidative stress and apoptosis, with decreased GSH levels in 50 mM glucose-treated VL-17A cells.",
            "output": [
                "Does gSH protect against oxidative stress and toxicity in VL-17A cells exposed to high glucose?"
            ]
        },
        {
            "id": "task847-24ec8f9ecb0e481fa93f2b5512d35e90",
            "input": "Sirtuin 3 (Sirt3), one of the seven Sirtuins family members, plays critical roles in the progression of multiple cancer types. However, its role in the prognosis of hepatocellular carcinoma (HCC) has not yet been investigated systematically.', 'The correlation of Sirtuins expression with prognosis of HCC was determined by immunohistochemistry (IHC) in a large HCC patient cohort (n = 342). Expression of Sirt3 in tumoral and peritumoral tissues of HCC patients were further determined by western blotting (WB).', 'IHC and WB studies both showed a decreased expression of Sirt3 in tumoral tissues compared with peritumoral tissues (P = 0.003 for IHC, P = 0.0042 for WB). Decreased expression of Sirt3 in both tumoral and peritumoral tissues was associated with increased recurrence probability and decreased overall survival rate by univariate analyses (intratumoral Sirt3: P = 0.011 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.017 for TTR, P = 0.023 for OS), the prognostic value was strengthened by multivariate analyses (intratumoral Sirt3: P = 0.031 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.047 for TTR, P = 0.031 for OS). Intratumoral Sirt3 also showed a favorable prognostic value in patients with BCLC stage A (TTR, P = 0.011; OS, P < 0.001). In addition, we found that IHC studies of other sirtuin members showed a decreased expression of Sirt2, Sirt4 and Sirt5 and an increased expression of Sirt1, Sirt6 and Sirt7 in intratumoral tissues compared with peritumoral tissues. In contrast to Sirt3, other members did not showed a remarkable correlation with HCC prognosis.",
            "output": [
                "Is down-regulation of sirtuin 3 associated with poor prognosis in hepatocellular carcinoma after resection?"
            ]
        },
        {
            "id": "task847-159137fe3e4b4afebbb94e8f5fc52335",
            "input": "Most melanomas harbor oncogenic BRAF(V600) mutations, which constitutively activate the MAPK pathway. Although MAPK pathway inhibitors show clinical benefit in BRAF(V600)-mutant melanoma, it remains incompletely understood why 10% to 20% of patients fail to respond. Here, we show that RAF inhibitor-sensitive and inhibitor-resistant BRAF(V600)-mutant melanomas display distinct transcriptional profiles. Whereas most drug-sensitive cell lines and patient biopsies showed high expression and activity of the melanocytic lineage transcription factor MITF, intrinsically resistant cell lines and biopsies displayed low MITF expression but higher levels of NF-\u03baB signaling and the receptor tyrosine kinase AXL. In vitro, these MITF-low/NF-\u03baB-high melanomas were resistant to inhibition of RAF and MEK, singly or in combination, and ERK. Moreover, in cell lines, NF-\u03baB activation antagonized MITF expression and induced both resistance marker genes and drug resistance. Thus, distinct cell states characterized by MITF or NF-\u03baB activity may influence intrinsic resistance to MAPK pathway inhibitors in BRAF(V600)-mutant melanoma.",
            "output": [
                "Does a melanoma cell state distinction influence sensitivity to MAPK pathway inhibitors?"
            ]
        },
        {
            "id": "task847-e3971455491446d986f6f5e412d13add",
            "input": "A scale for the Assessment and Rating of Ataxia (SARA) was developed for evaluation of autosomal dominant cerebellar ataxias (ADCA) and was also recommended for clinical trials of Friedreich's ataxia patients (FRDA). FRDA, unlike ADCA, is characterized as being a sensory type of ataxia for which the disease-specific Friedreich ataxia rating scale (FARS) was developed. The objective of this study was to determine whether SARA and FARS scores are associated with posturographic parameters in FRDA patients.\", 'Adult patients with genetically confirmed FRDA (n=11) and ADCA (n=13) were evaluated by SARA, FARS and posturography.', \"FRDA patients' postural stability parameters, in stance with visual control, correlated with balance impairment in FARS (r=0.622; p<0.05) and SARA (r=0.735; p<0.05). Without visual control, only FARS correlated with balance impairment (r=0.732; p<0.05).",
            "output": [
                "Is application of a Scale for the Assessment and Rating of Ataxia ( SARA ) in Friedreich 's ataxia patients according to posturography limited?"
            ]
        },
        {
            "id": "task847-a7ff12bac53041f5a81077b1e46e47c1",
            "input": "The present study investigated the effects of continuous theta-burst stimulation (cTBS) over primary somatosensory (SI) and motor (M1) cortices on motor-evoked potentials (MEPs) and short-latency afferent inhibition (SAI).', 'MEPs and SAI were recorded from the first dorsal interosseous (FDI) muscle of the right hand following 30Hz cTBS over left-hemisphere SI and M1 delivered to the same participants in separate sessions. Measurements were taken before and up to 60min following cTBS.', 'CTBS over M1 suppressed MEPs and did not alter SAI. In contrast cTBS over SI facilitated MEPs and decreased median and digital nerve evoked SAI.",
            "output": [
                "Does continuous theta-burst stimulation over primary somatosensory cortex modulate short-latency afferent inhibition?"
            ]
        },
        {
            "id": "task847-ec0ca9f638fe48bf8bf4e4b55a95198e",
            "input": "Extended partial hepatectomy (PH) in patients is leading to portal hyperperfusion but reduced hepatic arterial perfusion (HAP), and is invariably causing focal hepatic venous outflow obstruction (FHVOO). We observed in a rat model that PH in combination with right median hepatic vein ligation (RMHV-L) caused confluent parenchymal necrosis interspersed with viable portal tracts in the obstructed territory and large sinusoidal vascular canals in the border zone. Lack of HAP impaired the spontaneous course of recovery in terms of enlarged parenchymal necrosis, delayed regeneration, and the absence of draining vascular canals. We aimed to investigate whether pharmacological intervention modulates the imbalance between portal venous and hepatic arterial inflow, aggravates the liver damage, and delays the recovery process after FHVOO in liver-resected rats.', 'Male Lewis rats were subjected to 70% PH and RMHV-L. Molsidomine or NG-nitro-L-arginine methyl ester (L-NAME) or saline were applied daily. Hepatic damage, microcirculation, regeneration, and vascular remodeling were evaluated at postoperative days 1, 2, and 7. Animals subjected to RMHV-L only were used as \"no HAP\" control.', 'Significant increase of portal venous inflow with a concomitant decrease in HAP was observed in all groups after PH. Molsidomine treatment did neither affect hepatic hemodynamics nor the spontaneous recovery. In contrast, L-NAME treatment further decreased HAP which impaired hepatic microcirculation, aggravated parenchymal damage, decelerated recovery, and impaired the formation of sinusoidal canals.",
            "output": [
                "Does reduced hepatic arterial perfusion impair the recovery from focal hepatic venous outflow obstruction in liver-resected rats?"
            ]
        },
        {
            "id": "task847-44a6e119bf6440e0a243538983a0c225",
            "input": "Previous studies have shown the beneficial effects of enriched environment (EE) in rescuing behavioral deficits such as pre-pulse inhibition and locomotor hyperactivity associated with N-methyl-D-aspartate (NMDA) receptor blockade; however, cognitive deficits remain unresponsive.', 'We designed experiments to determine the consequences of raising rat pups in an EE on several behavioral aberrations, mainly cognitive deficits, observed in rats postnatally exposed to MK-801 (NMDA receptor antagonist).', 'Male Wistar rats were injected with MK-801 (1\\xa0mg/kg) from postnatal day (P) 6-10. Rat pups were housed in an EE from birth up to the time of behavioral experiments at P28-34. The effects of EE in correcting MK-801-associated behaviors were assessed by rotarod, wire grip, open filed, and Morris water maze tests.', 'We found that EE not only has beneficial effects on cognitive performance of normal rats but also prevents spatial learning and memory deficits in Morris water maze induced by MK-801. Postnatal MK-801 treatment also led to motor deficits both in wire grip and accelerating rotarod tests. These deficits were not observed in MK-801-treated rats raised in EE. In the open field test, EE prevented increase in \"frequency of grooming\" and decrease in \"time spent in the center\" associated with MK-801.",
            "output": [
                "Does enriched environment prevent cognitive and motor deficits associated with postnatal MK-801 treatment?"
            ]
        },
        {
            "id": "task847-a9577b14729942c6905a10ac3b73b8b9",
            "input": "The genus Fusarium comprises a heterogeneous group of fungi important for agriculture. Fusarium solani f. sp. eumartii (F. eumartii), historically considered to be a fungal pathogen of potato, has also been associated with tomato disease. Currently, chitosan and its derivatives have been receiving more attention as environmentally friendly antimicrobial compounds in sustainable practices. The aim of the present work was to characterize downstream events associated with the mode of action of chitosan, including nitrosative reactive species, in order to identify new biomarkers of its cytotoxic action.', 'Data indicated that chitosan-mediated nitric oxide (NO) production might lead to conidial death, concomitant with the strong reduction in fungal pathogenicity in tomato plants. Following chitosan applications, a notably dose-dependent reduction in conidial viability was demonstrated in F. eumartii. Thereafter, the infectivity of chitosan-treated spores was tested by a bioassay using tomato seedlings.",
            "output": [
                "Is nitric-oxide-mediated cell death triggered by chitosan in Fusarium eumartii spores?"
            ]
        },
        {
            "id": "task847-cfab53bf22bd4fbda0a930bdf640d99e",
            "input": "A protected block curriculum (PBC) with postcurriculum examinations for all surgical residents has been provided to assure coverage of core curricular topics. Biannual assessment of resident competency will soon be required by the Next Accreditation System.', 'To identify opportunities for early medical knowledge assessment and interventions, we examined whether performance in postcurriculum multiple-choice examinations (PCEs) is predictive of performance in the American Board of Surgery In-Training Examination (ABSITE) and clinical service competency assessments.', 'Retrospective single-institutional education research study.', 'Academic general surgery residency program.', 'A total of 49 surgical residents.', 'Data for PGY1 and PGY2 residents participating in the 2008 to 2012 PBC are included. Each resident completed 6 PCEs during each year.', 'The results of 6 examinations were correlated to percentage-correct ABSITE scores and clinical assessments based on the 6 Accreditation Council for Graduate Medical Education core competencies. Individual ABSITE performance was compared between PGY1 and PGY2. Statistical analysis included multivariate linear regression and bivariate Pearson correlations.', 'A total of 49 residents completed the PGY1 PBC and 36 completed the PGY2 curriculum. Linear regression analysis of percentage-correct ABSITE and PCE scores demonstrated a statistically significant correlation between the PGY1 PCE 1 score and the subsequent PGY1 ABSITE score (p = 0.037, \u03b2 = 0.299). Similarly, the PGY2 PCE 1 score predicted performance in the PGY2 ABSITE (p = 0.015, \u03b2 = 0.383). The ABSITE scores correlated between PGY1 and PGY2 with statistical significance, r = 0.675, p = 0.001. Performance on the 6 Accreditation Council for Graduate Medical Education core competencies correlated between PGY1 and PGY2, r = 0.729, p = 0.001, but did not correlate with PCE scores during either years.",
            "output": [
                "Do surgery residency curriculum examination scores predict future American Board of Surgery in-training examination performance?"
            ]
        },
        {
            "id": "task847-3718386e5f4d4dc0b2bacfd7d7a7dffd",
            "input": "Cardiac function is dependent on the coordinate activities of membrane ion channels, transporters, pumps, and hormone receptors to tune the membrane electrochemical gradient dynamically in response to acute and chronic stress. Although our knowledge of membrane proteins has rapidly advanced during the past decade, our understanding of the subcellular pathways governing the trafficking and localization of integral membrane proteins is limited and essentially unstudied in vivo. In the heart, to our knowledge, there are no in vivo mechanistic studies that directly link endosome-based machinery with cardiac physiology.', 'To define the in vivo roles of endosome-based cellular machinery for cardiac membrane protein trafficking, myocyte excitability, and cardiac physiology.', 'We identify the endosome-based Eps15 homology domain 3 (EHD3) pathway as essential for cardiac physiology. EHD3-deficient hearts display structural and functional defects including bradycardia and rate variability, conduction block, and blunted response to adrenergic stimulation. Mechanistically, EHD3 is critical for membrane protein trafficking, because EHD3-deficient myocytes display reduced expression/localization of Na/Ca exchanger and L-type Ca channel type 1.2 with a parallel reduction in Na/Ca exchanger-mediated membrane current and Cav1.2-mediated membrane current. Functionally, EHD3-deficient myocytes show increased sarcoplasmic reticulum [Ca], increased spark frequency, and reduced expression/localization of ankyrin-B, a binding partner for EHD3 and Na/Ca exchanger. Finally, we show that in vivo EHD3-deficient defects are attributable to cardiac-specific roles of EHD3 because mice with cardiac-selective EHD3 deficiency demonstrate both structural and electric phenotypes.",
            "output": [
                "Does eHD3-dependent endosome pathway regulate cardiac membrane excitability and physiology?"
            ]
        },
        {
            "id": "task847-87ab66115d104e958f1af1a8d37c3126",
            "input": "PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated.', 'The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model.', 'PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells.",
            "output": [
                "Does inhibition of autophagy enhance the cytotoxic effect of PA-MSHA in breast cancer?"
            ]
        },
        {
            "id": "task847-040ee9283d0c459bb9909f5c785fc6f0",
            "input": "Serotonin (5-HT) neurons mediate the ectopic release of dopamine (DA) induced by L-DOPA in the Parkinsonian brain. We hypothesized that the participation of noradrenalin transporters (NET) in the clearance of DA may account for the lower effect of L-DOPA in extrastriatal regions compared with the striatum.', 'Using a multisite intracerebral microdialysis approach, we tested the influence of the pharmacological blockade of NET and/or the destruction of noradrenalin (NE) fibers on DA and 5-HT release in the striatum, hippocampus (HIPP), substantia nigra pars reticulata (SNr) and prefrontal cortex (PFC) of 6-hydroxydopamine-lesioned rats.', 'L-DOPA (12 mg/kg, i.p.) increased DA extracellular levels to a lesser extent in the SNr, PFC and HIPP compared with the striatum. The NET blockers desipramine (10 mg/kg, i.p.) and reboxetine (3 mg/kg, i.p.) potentiated L-DOPA effect in the PFC, SNr and HIPP but not in the striatum. The NE neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg, i.p. 1 week before dialysis experiment) potentiated L-DOPA effect in the SNr and HIPP. 5-HT extracellular levels were enhanced only when L-DOPA was combined to NET blockers.",
            "output": [
                "Do noradrenergic terminals regulate L-DOPA-derived dopamine extracellular levels in a region-dependent manner in Parkinsonian rats?"
            ]
        },
        {
            "id": "task847-38816e0edb614d829095bf07fa5aac27",
            "input": "Genome-wide association studies (GWAS) have demonstrated that the single nucleotide polymorphism (SNP) MAP3K1 rs889312 is a genetic susceptibility marker significantly associated with a risk of hormone-related tumors such as breast cancer. Considering steroid hormone-mediated signaling pathways have an important role in the progression of gastric cancer, we hypothesized that MAP3K1 rs889312 may be associated with survival outcomes in gastric cancer. The purpose of this study was to test this hypothesis.', 'We genotyped MAP3K1 rs889312 using TaqMan in 884 gastric cancer patients who received subtotal or total gastrectomy. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between MAP3K1 rs889312 genotypes and survival outcomes of gastric cancer.', 'Our findings reveal that the rs889312 heterozygous AC genotype was significantly associated with an increased rate of mortality among patients with diffuse-type gastric cancer (log-rank P\\u200a=\\u200a0.028 for AC versus AA/CC, hazard ratio [HR]\\u200a=\\u200a1.32, 95% confidence interval [CI]\\u200a=\\u200a1.03-1.69), compared to those carrying the homozygous variant genotypes (AA/CC). Additionally, univariate and multivariate Cox regression analysis demonstrate that rs889312 polymorphism was an independent risk factor for poor survival in these patients.",
            "output": [
                "Does a MAP3k1 SNP predict survival of gastric cancer in a Chinese population?"
            ]
        },
        {
            "id": "task847-36f06417026c426fa93d01abaa01dad2",
            "input": "Coronavirus membrane (M) proteins are capable of interacting with nucleocapsid (N) and envelope (E) proteins. Severe acute respiratory syndrome coronavirus (SARS-CoV) M co-expression with either N or E is sufficient for producing virus-like particles (VLPs), although at a lower level compared to M, N and E co-expression. Whether E can release from cells or E/N interaction exists so as to contribute to enhanced VLP production is unknown. It also remains to be determined whether E palmitoylation or disulfide bond formation plays a role in SARS-CoV virus assembly.', 'SARS-CoV N is released from cells through an association with E protein-containing vesicles. Further analysis suggests that domains involved in E/N interaction are largely located in both carboxyl-terminal regions. Changing all three E cysteine residues to alanines did not exert negative effects on E release, E association with N, or E enhancement of VLP production, suggesting that E palmitoylation modification or disulfide bond formation is not required for SARS-CoV virus assembly. We found that removal of the last E carboxyl-terminal residue markedly affected E release, N association, and VLP incorporation, but did not significantly compromise the contribution of E to efficient VLP production.",
            "output": [
                "Is sARS-CoV envelope protein palmitoylation or nucleocapid association required for promoting virus-like particle production?"
            ]
        },
        {
            "id": "task847-744fc9f607ea4ea1b3a88aa3386d6e82",
            "input": "The incidence of gastric cancer after successful Helicobacter pylori eradication has been increasing. We previously reported that epithelium with low-grade atypia (ELA) appeared on the surface of gastric cancer after H. pylori eradication. Here, we investigate the clinical and biological characteristics of such ELA.', 'We studied 27 cases of gastric cancer detected after successful H. pylori eradication therapy. We examined the prevalence of ELA among these cases and its significance for endoscopic discovery after H. pylori eradication. We additionally investigated the mucus, p53 and Ki67 expressions in ELA.', 'Epithelium with low-grade atypia that continuous with the gastric tumor was detected in 22 of 27 cases (81%), a significantly greater percentage than that for controls (p < 0.01). We found that gastric-type mucin was frequently expressed in this epithelium. Neither p53- nor Ki67-positive cells were found in ELA, irrespective of their expression in tumor tissue. The presence of ELA was positively correlated with the clinical interval between H. pylori eradication and gastric cancer detection.",
            "output": [
                "Does characteristic epithelium with low-grade atypia appear on the surface of gastric cancer after successful Helicobacter pylori eradication therapy?"
            ]
        },
        {
            "id": "task847-d1c18443fb3e479eaca69491279cfd36",
            "input": "Electrophysiological methods could provide important information about the neurophysiological status in Parkinson's disease (PD).\", 'To investigate the prolonged auditory P300 latency in PD and its association with the disease clinical stage.', 'Clinical profiles of 44 patients were evaluated and those in initial and advanced stages of PD were identified. The frequency of altered latencies, median of latencies in each stage, and correlation between latencies and motor and non-motor clinical features were analyzed. Latencies were considered altered when they were more than two standard deviations from the mean of controls, per age group.', 'It was verified 10% of alterations in initial stages and 31% in advanced. There was correlation between latencies and non-motor clinical features. Subjects older than 65, in advanced stages, presented a significant increase of latencies.",
            "output": [
                "Are delayed latencies of auditory evoked potential P300 associated with the severity of Parkinson 's disease in older patients?"
            ]
        },
        {
            "id": "task847-4e082a282d7f4404b840e6ddf8a769e6",
            "input": "The SARS coronavirus (SARS-CoV) 3a protein functions as an ion channel, induces apoptosis and is important for viral pathogenesis. It is expressed on the cell surface and contains a tyrosine-based sorting motif and a di-acidic motif, which may be crucial for its intracellular trafficking. However the role of these motifs is not fully understood in the case of 3a protein.', 'The subcellular distribution of the 3a protein was studied by immunofluorescence staining of cells transfected with wild type and mutant constructs along with markers for different intracellular compartments. Semi-quantitative RT-PCR was performed to estimate the mRNA where as western blotting was carried out to detect protein levels of wild type and mutant 3a proteins. In vitro transcription- translation was performed to estimate cell free protein synthesis.', 'While the wild type 3a protein is efficiently transported to the plasma membrane, the protein with mutations in the tyrosine and valine residues within the YXXV motif (\u0394YXX\u03a6) accumulated in the Golgi compartment. However the 3a protein with mutations within the EXD di-acidic motif (\u0394EXD) showed an intracellular distribution similar to the wild type protein. Increased retention of the \u0394YXX\u03a6 protein in the Golgi compartment also increased its association with lipid droplets. The \u0394YXX\u03a6 protein also expressed at significantly lower levels compared to the wild type 3a protein, which was reversed with Brefeldin A and Aprotinin.",
            "output": [
                "Is the YXX\u03a6 motif within the severe acute respiratory syndrome coronavirus ( SARS-CoV ) 3a protein crucial for its intracellular transport?"
            ]
        },
        {
            "id": "task847-4d8e6942d69e414dbe58bfbc822e12d2",
            "input": "Although anti-angiogenic therapy (AATx) holds great promise for treatment of malignant gliomas, its therapeutic efficacy is not well understood and can potentially increase the aggressive recurrence of gliomas. It is essential to establish sensitive, noninvasive biomarkers that can detect failure of AATx and tumor recurrence early so that timely adaptive therapy can be instituted. We investigated the efficacy of MRI biomarkers that can detect response to different classes of AATxs used alone or in combination with radiation.', 'Murine intracranial glioma xenografts (NOD/SCID) were treated with sunitinib, VEGF-trap or B20 (a bevacizumab equivalent) alone or in combination with radiation. MRI images were acquired longitudinally before and after treatment, and various MRI parameters (apparent diffusion coefficient, T1w + contrast, dynamic contrast-enhanced [DCE], initial area under the contrast enhancement curve, and cerebral blood flow) were correlated to tumor cell proliferation, overall tumor growth, and tumor vascularity.', 'Combinatorial therapies reduced tumor growth rate more efficiently than monotherapies. Apparent diffusion coefficient was an accurate measure of tumor cell density. Vascular endothelial growth factor (VEGF)-trap or B20, but not sunitinib, resulted in significant reduction or complete loss of contrast enhancement. This reduction was not due to a reduction in tumor growth or microvascular density, but rather was explained by a reduction in vessel permeability and perfusion. We established that contrast enhancement does not accurately reflect tumor volume or vascular density; however, DCE-derived parameters can be used as efficient noninvasive biomarkers of response to AATx.",
            "output": [
                "Do mRI biomarkers identify the differential response of glioblastoma multiforme to anti-angiogenic therapy?"
            ]
        },
        {
            "id": "task847-e24119e14acf45d6a3b28d0849879713",
            "input": "Chemerin has been implicated to play opposing roles, either pro-inflammatory or anti-inflammatory, in various tissue inflammation processes primarily through the regulation of tissue recruitment of immune cells. However, the effect of chemerin in allergic asthma has not yet been explored. We sought to investigate the role of chemerin in the murine model of allergic asthma and explore the underlying mechanism.', 'We examined the effect of intranasal (i.n.) administration of chemerin during antigen challenge in murine models of asthma. Moreover, we examined whether administration of CCL2 or bone marrow-derived dendritic cells (BMDCs) transfer reversed the effects of chemerin on ovalbumin-induced asthma. We finally examined the effect of chemerin on CCL2 expression in activated lung epithelial cells in vitro.', 'The administration of chemerin attenuated allergic airway inflammation and airway hyperreactivity during antigen challenge. Chemerin treatment caused significant decreases in BALF CD4(+) T-cell accumulation and mRNA expression of Th2-attracting chemokines, CCL17 and CCL22, which was accompanied by significantly decreased BALF CD11c(+) CD11b(+) inflammatory DC accumulation and CCL2 production. Furthermore, airway administration of exogenous CCL2 or adoptive transfer of CD11c(+) CD11b(+) BMDCs abrogated the suppressive effects of chemerin on allergic asthma. Finally, in vitro study showed that chemerin inhibited CCL2 secretion by low-dose LPS-stimulated lung epithelial cells, which led to decreased chemotaxis of BMDCs.",
            "output": [
                "Does chemerin suppress murine allergic asthma by inhibiting CCL2 production and subsequent airway recruitment of inflammatory dendritic cells?"
            ]
        },
        {
            "id": "task847-9d3b82eac04447349907ce46d784b951",
            "input": "Morphogenesis of the zebrafish neural tube requires the coordinated movement of many cells in both time and space. A good example of this is the movement of the cells in the zebrafish neural plate as they converge towards the dorsal midline before internalizing to form a neural keel. How these cells are regulated to ensure that they move together as a coherent tissue is unknown. Previous work in other systems has suggested that the underlying mesoderm may play a role in this process but this has not been shown directly in vivo.', 'Here we analyze the roles of subjacent mesoderm in the coordination of neural cell movements during convergence of the zebrafish neural plate and neural keel formation. Live imaging demonstrates that the normal highly coordinated movements of neural plate cells are lost in the absence of underlying mesoderm and the movements of internalization and neural tube formation are severely disrupted. Despite this, neuroepithelial polarity develops in the abnormal neural primordium but the resulting tissue architecture is very disorganized.",
            "output": [
                "Is mesoderm required for coordinated cell movements within zebrafish neural plate in vivo?"
            ]
        },
        {
            "id": "task847-52851e869e584e488ee976b86e96771d",
            "input": "Although drug-eluting stents (DES) have been widely used for the treatment of coronary artery disease, they potentially increase the risk of late thrombosis. It is, therefore, desirable to establish a strategy to stimulate reendothelialization. Endothelial injury models have been widely used to analyze the mechanisms of coronary restenosis. However, animal models deployed with coronary stents in the blood vessels are necessary to accurately analyze the mechanisms of coronary restenosis and late thrombosis because persistent inflammation occurs around the coronary stents.', 'Coronary stents were implanted into rat abdominal aorta and adipose tissue-derived stem cells (ASC) were administered from the adventitial side. Reendothelialization was then visualized by Evans blue staining, and neointimal formation was analyzed histologically. ASC significantly stimulated reendothelialization and inhibited neointimal formation in bare metal stents (BMS)-implanted aorta. In addition, ASC promoted reendothelialization in DES-implanted aorta; however, the effects were weaker than in BMS-implanted aorta. Among the cytokines that ASC produce, adrenomedullin (AM) significantly stimulated reendothelialization and inhibited neointimal formation in BMS-implanted aorta, when an adenovirus expressing AM was administered from the adventitial side.",
            "output": [
                "Do adipose-derived stem cells stimulate reendothelialization in stented rat abdominal aorta?"
            ]
        },
        {
            "id": "task847-6f0420f3bf724d67b9f4049a2e786ae0",
            "input": "To assess whether differential expression of caspase-3 in paired metastatic lymph nodes (LNs) is prognostic of survival in patients with resectable esophageal squamous cell carcinoma (ESCC).', 'Capases-3 expression was evaluated immunohistochemically in 122 pairs of primary ESCCs and regional metastatic LNs assembled on tissue microarrays. The impact of caspase-3 expression on survival outcomes was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model.', 'The level of caspase-3 expression was significantly higher in LN metastases than in primary tumors (P < 0.001). Caspase-3 expression in the primary tumors was associated with longer median survival (23 mo vs 21 mo, P = 0.033), whereas higher expression in paired metastatic LNs was associated with shorter median survival (20 mo vs 22 mo, P = 0.043). Multivariate analysis showed that both were independent prognostic factors.",
            "output": [
                "Is caspase-3 expression in metastatic lymph nodes of esophageal squamous cell carcinoma prognostic of survival?"
            ]
        },
        {
            "id": "task847-37adec535815425692fc5b61f5696cfd",
            "input": "Oxylipins, including eicosanoids, are highly bioactive molecules endogenously produced from polyunsaturated fatty acids. Oxylipins play a key role in chronic disease progression. It is possible, but unknown, if oxylipin concentrations change with the consumption of functional foods or differ with subject age.', 'Therefore, in a parallel comparator trial, 20 healthy individuals were recruited into a younger (19-28years) or older (45-64years) age group (n=10/group). Participants ingested one muffin/day containing 30g of milled flaxseed (6g alpha-linolenic acid) for 4weeks. Plasma oxylipins were isolated through solid phase extraction, analyzed with HPLC-MS/MS targeted lipidomics, and quantified with the stable isotope dilution method.', 'At baseline, the older group exhibited 13 oxylipins \u22652-fold the concentration of the younger group. Specifically, pro-inflammatory oxylipins 5-hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid were significantly greater in the older (1.1\u00b10.23nM, 5.6\u00b10.84nM, and 4.5\u00b10.58nM, respectively) versus the younger group (0.34\u00b10.12nM, 3.5\u00b10.33nM, and 3.0\u00b10.24nM, respectively) (p<0.05). After 4weeks of flaxseed consumption the number of oxylipins that were \u22652-fold higher in the older versus the younger group was reduced to 3. 5-Hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid decreased in the older group to concentrations equivalent to the younger group after flaxseed consumption.",
            "output": [
                "Are elevated levels of pro-inflammatory oxylipins in older subjects normalized by flaxseed consumption?"
            ]
        },
        {
            "id": "task847-7a8aa886a692454d8757d9248a729fcd",
            "input": "To examine the relationship between statin use in Chinese patients with intracerebral hemorrhage (ICH) during their hospitalization and the outcomes.', 'Data were collected from the China National Stroke Registry. Good functional outcome was defined by a modified Rankin Scale score between 0-2. Functional outcome and rate of mortality at 3 months and 1 year were compared between ICH patients on statin and those without it during their hospitalization. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the multivariable logistic regression model adjusted for baseline risk factors.', 'Among 3218 consecutive ICH patients from 2007 to 2008, 220 (6.8%) were on statin during their hospitalization. Compared with those without statin, patients on statin were younger, had more stroke risk factors but lower stroke severity. ICH patients on statin had better functional outcome at 3 months (OR 2.24, 95% CI 1.49-3.36) and at 1 year (OR 2.04, 95% CI 1.37-3.06). They also had lower rate of mortality at 3 months (OR 0.44, 95% CI 0.22-0.87) and 1 year (OR 0.49, 95% CI 0.27-0.86).",
            "output": [
                "Does use of statin during hospitalization improve the outcome after intracerebral hemorrhage?"
            ]
        },
        {
            "id": "task847-5687b3272d1946968fcb8a58e779bc48",
            "input": "To determine microRNA (miRNA) expression in human blastocysts relative to advanced maternal age and chromosome constitution.', \"Cryopreserved human blastocysts were warmed and underwent a trophectoderm biopsy for comprehensive chromosomal screening. Select blastocysts were then lysed, reverse transcribed, and pre-amplified prior to running real-time PCR. Statistical analysis was performed using an internal constant housekeeping miRNA. Significant microRNA's of interest were then analyzed for their predicted genes and biological pathways. Additional cryopreserved blastocysts were warmed and stained for the SIRT1 protein for validation.\", 'Human blastocysts exhibit unique miRNA expression profiles in relation to maternal age and chromosome constitution. miR-93 was exclusively expressed in blastocysts from women in their forties and further up-regulated with an abnormal chromosome complement. Up-regulated miR-93 resulted in an inverse down-regulation of targets like SIRT1, resulting in reduced oxidative defense.",
            "output": [
                "Do human blastocysts exhibit unique microrna profiles in relation to maternal age and chromosome constitution?"
            ]
        },
        {
            "id": "task847-90f750ef8f744d62a62914bfdc5827d5",
            "input": "Hostility may be associated with greater systemic inflammation. However, contradictory evidence exists. Certain individuals or dimensions of hostility may be more susceptible to these effects. Main and interactive effects of hostility with sex and/or age were evaluated on markers of inflammation, independently of traditional risk factors for coronary artery disease.', '199 healthy men (81) and women (118), aged 20-64 years (M=41 \u00b1 11 years) were recruited. Hostility was assessed using the Cook-Medley Hostility Inventory (CMHo) and ecological momentary assessments (EMA) of quarrelsome behavior and angry affect in daily living. Blood samples were drawn to measure inflammatory activity (Il-6, TNF-\u03b1, hsCRP, Il-8, Il-10, Il-18, MCP-1) and lipid oxidation (Myeloperoxidase; MPO). Correlations and hierarchical regression analyses were performed controlling for pertinent behavioral, psychological, medical, and socio-demographic factors.', 'Significant univariate associations emerged between CMHo and Il-6, TNF-\u03b1, MCP-1 (p<.05). Hierarchical regressions showed interactions of hostility with sex (Il-6, TNF-\u03b1; p<.05) and age (hsCRP, Il-6, TNF-\u03b1; p<.05). For example, in simple slope analyses, hostility was positively related to TNF-\u03b1 in women (b=0.009, p=0.006) but not men. Greater hostility was also related to greater Il-6 levels among younger women (b=. 027, p=0.000).",
            "output": [
                "Is the relation between hostility and concurrent levels of inflammation sex , age , and measure dependent?"
            ]
        },
        {
            "id": "task847-c8f4bbad14eb485eb9257624adc97de9",
            "input": "Metabolic syndrome (MetS) and depression have become two prevalent diseases worldwide, whose interaction needs further investigation. Dietary treatment for weight loss in patients with MetS may improve depressive manifestations, however, the precise interactive pathways remain uncertain. Therefore, the aim of this study was to examine the effects of a hypocaloric diet designed to reduce MetS features on self-perceived depression and the possible underlying factors.', 'Sixty subjects (Age: 50 \u00b1 1 y; BMI: 36.1 \u00b1 0.6 kg/m(2)) with MetS were selected from the RESMENA study (control and intervention) after they completed the 6-months hypocaloric treatment and rated for depressive symptoms using the Beck Depression Inventory (BDI). Anthropometric and biochemical measurements including leptin, C-reactive protein (CRP) and insulin levels were evaluated.', 'Depressive symptoms decreased during the weight loss intervention, with no differences between both dietary groups (control group -4.2 \u00b1 0.8 vs RESMENA group -3.2 \u00b1 0.6, P = 0.490). The number of criteria of the MetS was higher among subjects with more somatic-related depressive symptoms at baseline (B = 1.032, P-trend = 0.017). After six months of dietary treatment, body weight decreased in all subjects (-8.7%; confidence interval (95% CI)\\u2009= 7.0-9.7) and also self-perceived depression (-37.9%; 95% CI = 2.7-4.9), as well as circulating leptin (-20.1%; 95% CI = 1.8-6.8), CRP (-42.8%; 95% CI = 0.6-3.0) and insulin (-37.7%; 95% CI = 4.1-7.2) concentrations. The decrease in BDI was significantly associated with declines in body fat mass (B = 0.34, 95% CI = 0.11-0.56) and also with the decrease in leptin (B = 0.16, 95% CI = 0.04-0.28) and CRP (B = 0.24, 95% CI = 0.01-0.46) concentrations.",
            "output": [
                "Is a decline in inflammation associated with less depressive symptoms after a dietary intervention in metabolic syndrome patients : a longitudinal study?"
            ]
        },
        {
            "id": "task847-735b7de3ffb548ed861a3c59ba947ad7",
            "input": "Allopregnanolone (3\u03b1-hydroxy-5\u03b1-pregnan-20-one) is a neurosteroid which has an inhibitory function through interaction with the GABAA receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy covary with concurrent self-rated symptoms of depression and anxiety.', 'Ninety-six women in pregnancy weeks 37-40 rated symptoms of depression and anxiety with the Montgomery-\u00c5sberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory. Their serum allopregnanolone was analyzed by Celite chromatography and radioimmunoassay.', \"Ten women had elevated depression scores (MADRS-S \u2265 13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the normal range (39.0 \u00b1 17.9 vs. 54.6 \u00b1 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson's correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy.",
            "output": [
                "Is low serum allopregnanolone associated with symptoms of depression in late pregnancy?"
            ]
        },
        {
            "id": "task847-d058b2993bb34cdd8ee3bf7118ea3322",
            "input": "Obstructive sleep apnea (OSA) is a common disorder characterized by chronic intermittent hypoxia (CIH). OSA is prevalent in obese subjects and is associated with endothelial dysfunction and cardiovascular disorders. We tested the hypothesis that the deleterious effects of IH could be further modulated by diet-induced obesity.', 'Thirty adult (8-10 weeks) male C57BL/6J mice were divided into four groups. Mice were subjected to CIH or intermittent air (IA) for 12h a day and fed either a high fat (HF) or a low fat control diet (CD) for 6weeks. We analyzed endothelial function using a wire myograph, and measured markers of oxidative stress (plasma malondialdehyde (MDA) and total antioxidant capacity (TAC)) using colorimetrical assays. We also measured C-reactive protein (CRP) using ELISA and endothelial nitric oxide (eNOS) gene expression using real time PCR.', 'Stimulated endothelial dependent dilation was significantly impaired only in the group fed high fat diet and subjected to CIH (Emax: HFIH 78\u00b12%, p<0.0001) when compared to the other groups (Emax: HFIA 95\u00b10.7%, CDIH 94\u00b12%, CDIA 97\u00b11%). Also basal endothelial dependant dilation was attenuated in the HFIH group compared to the HFIA group (Emax: HFIH: 179\u00b110% vs. HFIA: 149\u00b111% in the presence of L-NAME). Levels of MDA were elevated in the CDIH group when compared to CDIA (0.68\u00b10.04 vs. 0.41\u00b10.03 \u03bcM, p<0.05) but were greatest in the HFIH group (0.83\u00b10.08 \u03bcM, p<0.05). However, there was no significant increase in MDA levels in the HFIA group (0.45\u00b10.03 \u03bcM, p=NS) when compared to all other groups. Similar effects were observed with CRP levels; CRP levels were significantly higher in the CDIH group compared with intermittent air (10.39\u00b10.38 vs. 8.70\u00b10.21 \u03bcg/ml, p<0.05) but the HFIH had the greatest levels of CRP (11.87\u00b10.31 \u03bcg/ml, p<0.05). In the HFIA group, CRP levels were not elevated (9.96\u00b10.37 \u03bcg/ml, p=NS). Nevertheless, total antioxidant capacity and eNOS gene expression were not significantly different in the groups.",
            "output": [
                "Does chronic intermittent hypoxia cause endothelial dysfunction in a mouse model of diet-induced obesity?"
            ]
        },
        {
            "id": "task847-83c15201e4a747b7a27e2664fc073f2e",
            "input": "To evaluate the expression of CXCR4, its ligand SDF-1, \u03b2-catenin and E-cadherin throughout the local tumor microenvironment of prostate cancer.', \"A total of 64 prostate cancer specimens, 24 frozen and 40 paraffin-embedded sections, were obtained from patients treated with radical prostatectomy for clinically localized cancer. Real-time RT-PCR was used for mRNA quantification of CXCR4 and SDF-1 in the tumor center (T), tumor front (F) and distant peritumoral tissue (D). Immunohistochemical analysis was used to investigate the expression patterns of CXCR4, E-cadherin and \u03b2-catenin. Clinical records of these patients were studied for follow-up data, and the prognostic value of these molecules' expression was statistically assessed.\", 'CXCR4 mRNA and protein were significantly increased at the tumor front as compared to distant tissue or tumor center. In comparison, SDF-1 mRNA level gradually increased from the tumor center to the distant peritumoral tissue. High CXCR4 at the tumor front was associated with high Gleason score. Low SDF-1 at the tumor front was associated with locally advanced cancer and disease recurrence. Moreover, high CXCR4 staining at the tumor front and increased cytosolic E-cadherin expression in the same location was associated with locally advanced disease.",
            "output": [
                "Is cXCR4 highly expressed at the tumor front but not in the center of prostate cancers?"
            ]
        },
        {
            "id": "task847-04274c7140e54615946cfbe5c5207d9a",
            "input": "In adipose tissue healing, angiogenesis is stimulated by adipose-derived stromal stem cells (ASCs). Ventral hernia repair (VHR) patients are at high risk for wound infections. We hypothesize that ASCs from VHR patients are less vasculogenic than ASCs from healthy controls.', 'ASCs were harvested from the subcutaneous fat of patients undergoing VHR by the component separation technique and from matched abdominoplasty patients. RNA and protein were harvested on culture days 0 and 3. Both groups of ASCs were subjected to hypoxic conditions for 12 and 24 hours. RNA was analyzed using qRT-PCR, and protein was used for western blotting. ASCs were also grown in Matrigel under hypoxic conditions and assayed for tubule formation after 24 hours.', 'Hernia patient ASCs demonstrated decreased levels of VEGF-A protein and vasculogenic RNA at 3 days of growth in differentiation media. There were also decreases in VEGF-A protein and vasculogenic RNA after growth in hypoxic conditions compared to control ASCs. After 24 hours in hypoxia, VHR ASCs formed fewer tubules in Matrigel than in control patient ASCs.",
            "output": [
                "Do adipose-derived mesenchymal stem cells from ventral hernia repair patients demonstrate decreased vasculogenesis?"
            ]
        },
        {
            "id": "task847-9b7264ae00d04bf9a8e3aeb0244a7341",
            "input": "Cadmium exposure was found to cause a decline in lung function among the general population, but these findings were limited to smokers and gender differences were not explored.', 'To examine the relationship between cadmium and chronic obstructive pulmonary disease (COPD) according to gender and smoking status in Korea.', 'Cross-sectional data from the Korean National Health and Nutrition Examination Survey from 2008 to 2011 were analyzed. COPD was defined by a pre-bronchodilator forced expiratory volume in 1s divided by forced vital capacity of <0.70. A logistic regression model was used to elucidate the association between blood cadmium levels and COPD according to gender and smoking status.', 'Among 3861 eligible participants, 3622 were included in the analysis. The prevalence of COPD demonstrated an increasing trend in males (P for trend<0.001), but not in females (P for trend=0.67). After adjusting for covariates, a higher blood cadmium level, but within the normal range, was associated with COPD in males, including those who had never-smoked (P for trend <0.001 and P for trend=0.008). However, a higher blood cadmium level was not significantly associated with COPD in females, including those who had never smoked (P for trend=0.39 and P for trend=0.43).",
            "output": [
                "Are blood cadmium levels associated with a decline in lung function in males?"
            ]
        },
        {
            "id": "task847-1db4de81cf2c41ab9d0b0c5a5bedd534",
            "input": "Patients affected by chronic lymphocytic leukemia (CLL) have an increased risk of developing a second cancer. There is not a definitive explanation for this phenomenon, although some hypotheses have been postulated. The aim of the present work was to assess the presence of second cancer in untreated patients with CLL who were cytogenetically characterized, and secondly to investigate if there is a correlation between the genetics of CLL and the emergence of second cancer.', 'We performed conventional cytogenetics and Fluorescent in situ hybridization analyses in a series of 106 patients.', 'We observed that nearly 8% of cases developed second cancer, mostly epithelial tumors. The majority of them presented two common features, del(13)(q14.3) and the presence of at least two genetic alterations.",
            "output": [
                "Does genetics of lymphocytes influence the emergence of second cancer in chronic lymphocytic leukemia?"
            ]
        },
        {
            "id": "task847-0d653cf683994d30b6e78c6eca6ef4fb",
            "input": "It is unknown whether hypoxia regulates aurora kinase A (AURKA), a serine/threonine kinase, in neuroblastoma to stimulate cell growth or migration. We sought to determine whether AURKA mediates hypoxia-induced regulation of neuroblastoma tumorigenicity.', 'Human neuroblastoma BE(2)-C cells were treated with CoCl2, a chemical hypoxia mimetic, and MLN8237, a pharmalogical inhibitor of AURKA, to assess cell viability, colony formation and transwell migration. Focal adhesion kinase (FAK) expression was analyzed after silencing of AURKA under normoxic vs. hypoxic conditions.', 'Hypoxia up-regulated expression of AURKA mRNA and protein. CoCl2 stimulated cell proliferation and migration, while inhibiting colony formation. MLN8237 reduced colony formation and cell migration. Silencing of AURKA reduced expression of FAK and pFAK under normoxia and hypoxia.",
            "output": [
                "Does targeting aurora kinase A inhibit hypoxia-mediated neuroblastoma cell tumorigenesis?"
            ]
        },
        {
            "id": "task847-77a815b2d64c45e3840f065f9dd40b55",
            "input": "Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion.', 'Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data.', 'We show that WNT5A signaling induces a Ca2+-dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro. Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM.",
            "output": [
                "Does wNT5A induce release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells?"
            ]
        },
        {
            "id": "task847-81ef0e4b81e94490b8cf5fc1decdc704",
            "input": "Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by severe joint erosion and systemic osteoporosis. Chronic T cell activation is a hallmark of RA, and agents that target the CD28 receptor on T cells, which is required for T cell activation, are being increasingly used as therapies for RA and other inflammatory diseases. Lymphocytes play complex roles in the regulation of the skeleton, and although activated T cells and B cells secrete cytokines that promote skeletal decline, under physiologic conditions lymphocytes also have key protective roles in the stabilization of skeletal mass. Consequently, disruption of T cell costimulation may have unforeseen consequences for physiologic bone turnover. This study was undertaken to investigate the impact of pharmacologic CD28 T cell costimulation blockade on physiologic bone turnover and structure.', 'C57BL6 mice were treated with CTLA-4Ig, a pharmacologic CD28 antagonist or with irrelevant control antibody (Ig), and serum biochemical markers of bone turnover were quantified by enzyme-linked immunosorbent assay. Bone mineral density and indices of bone structure were further measured by dual x-ray absorptiometry and micro-computed tomography, respectively, and static and dynamic indices of bone formation were quantified using bone histomorphometry.', 'Pharmacologic disruption of CD28 T cell costimulation in mice significantly increased bone mass and enhanced indices of bone structure, a consequence of enhanced bone formation, concurrent with enhanced secretion of the bone anabolic factor Wnt-10b by T cells.",
            "output": [
                "Does cTLA-4Ig-induced T cell anergy promote Wnt-10b production and bone formation in a mouse model?"
            ]
        },
        {
            "id": "task847-639bc6fecace44eab59b92d2f3fa9988",
            "input": "To assess the rapid improvement of insulin sensitivity and \u03b2-cell function following biliopancreatic diversion with duodenal switch (BPD-DS) and determine the role played by caloric restriction in these changes.', 'Standard meals were administrated before and on day 3, 4, and 5 after BPD-DS to measure total caloric intake, glucose excursion, insulin sensitivity, and secretion in matched type 2 diabetes and normoglycemic (NG) subjects. In a second set of study, other subjects with type 2 diabetes had the same meal tests prior to and after a 3-day caloric restriction identical to that observed after BPD-DS and then 3 days after actually undergoing BPD-DS.', 'Improvement of HOMA-IR occurred at day 3 after BPD-DS in diabetes and after 3 days of caloric restriction. The disposition index (DI) improved rapidly in diabetes after BPD-DS and to a similar extent after caloric restriction. DI was higher and did not change after BPD-DS in NG. Changes in glucagon-like peptide-1, gastric inhibitory peptide, peptide tyrosine tyrosine, ghrelin, and pancreatic polypeptide levels were not associated with modulation of DI in the participants.",
            "output": [
                "Does biliopancreatic diversion with duodenal switch improve insulin sensitivity and secretion through caloric restriction?"
            ]
        },
        {
            "id": "task847-031dcec8ef9940a1aefa65847bfec900",
            "input": "To identify the prevalence and correlates of personality disorder in a representative sample of the Jamaican population using the Jamaica Personality Disorder Inventory (JPDI).', 'A four-stage stratified random sampling method was used to obtain a representative population sample consisting of 1506 Jamaicans, M:F = 727 (48.3%):779 (51.7%), ages 18-64 years. A demographic questionnaire and the JPDI were administered to all participants.', \"Two-fifths of the population (41.4%) scored above the scale's cut-point indicating a diagnosis of personality disorder with the level of severity ranging from mild to severe. Persons with personality disorder were significantly more likely to be single (63%), male (60%), between the ages 18 and 44 years (77%) and of a lower socio-economic status (65%) (p < 0.50 to p < 0.001).",
            "output": [
                "Does prevalence and correlate of personality disorder in the Jamaican population?"
            ]
        },
        {
            "id": "task847-4980480fbf6647e3b9bc9ca1cd16b1ed",
            "input": "To test whether a brief mindfulness meditation training intervention buffers self-reported psychological and neuroendocrine responses to the Trier Social Stress Test (TSST) in young adult volunteers. A second objective evaluates whether pre-existing levels of dispositional mindfulness moderate the effects of brief mindfulness meditation training on stress reactivity.', 'Sixty-six (N=66) participants were randomly assigned to either a brief 3-day (25-min per day) mindfulness meditation training or an analytic cognitive training control program. All participants completed a standardized laboratory social-evaluative stress challenge task (the TSST) following the third mindfulness meditation or cognitive training session. Measures of psychological (stress perceptions) and biological (salivary cortisol, blood pressure) stress reactivity were collected during the social evaluative stress-challenge session.', 'Brief mindfulness meditation training reduced self-reported psychological stress reactivity but increased salivary cortisol reactivity to the TSST, relative to the cognitive training comparison program. Participants who were low in pre-existing levels of dispositional mindfulness and then received mindfulness meditation training had the greatest cortisol reactivity to the TSST. No significant main or interactive effects were observed for systolic or diastolic blood pressure reactivity to the TSST.",
            "output": [
                "Does brief mindfulness meditation training alter psychological and neuroendocrine responses to social evaluative stress?"
            ]
        },
        {
            "id": "task847-f49fde48dd684a9a802394cd89257cbc",
            "input": "Prolactin levels have been shown to be increased by different types of psychosocial stress. Since burnout is a consequence of long-term psychosocial stress, prolactin levels might also be affected in burnout. The aim of this study was to investigate whether there are differences in prolactin levels between individuals who report burnout and others.', 'Morning fasting serum prolactin levels were compared between individuals who reported burnout (24 men and 25 women) and individuals who reported no burnout (25 men and 13 women). Women were tested in the follicular phase of the menstrual cycle. Men and women were analysed separately.', 'Men who reported burnout exhibited significantly higher (34%) serum prolactin levels compared to men who reported no burnout. The prolactin levels in women who reported burnout were not different from the levels in the women who reported no burnout before or after adjusting for estradiol levels.",
            "output": [
                "Is burnout associated with elevated prolactin levels in men but not in women?"
            ]
        },
        {
            "id": "task847-40edb04ab67d4142aa9d2437635f6c2c",
            "input": "Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology is an effective tool to diagnose pancreatic ductal adenocarcinoma (PDA). Standard morphological criteria are usually reliable. When contaminating gastrointestinal (GI) epithelial cells are prevalent among neoplastic cells, these can be highlighted by carcinoembryonic antigen (CEA) staining. CD10 is a cell-surface metallopeptidase normally expressed by the GI epithelial apical border, whose expression is decreased or lost in PDA. We included CD10 in a panel, together with CEA, to discriminate the GI contaminant cells from PDA cells on cell blocks.', 'Eight cases of EUS-FNA of PDA, featuring both contaminating GI cells and neoplastic cells, whose corresponding cell blocks were available for immunostaining, were selected. CD10 and CEA were stained on cell blocks by standard methods.', 'CD10 strongly labelled only the GI cells, with a well-defined apical membrane signal; conversely, GI cells did not show CEA staining; benign duodenal cells were faintly labelled in only one case. Malignant cells were positive for CEA and negative for CD10, with the exception of one case with labelled neoplastic cells with weak diffuse cytoplasmic positivity. CD10 apical membrane staining was a feature only seen in benign GI cells.",
            "output": [
                "Is cD10 useful to identify gastrointestinal contamination in endoscopic ultrasound-guided fine needle aspiration ( EUS-FNA ) cytology from pancreatic ductal adenocarcinoma?"
            ]
        },
        {
            "id": "task847-1c7d9f6301f441298869048915ffe83b",
            "input": "To introduce an elastomeric continuous infusion pump for pain control after outpatient orbital implant surgery.', 'Retrospective, noncomparative consecutive case series of all patients undergoing enucleation, evisceration, or secondary orbital implantation using the On-Q pain system between August 2004 and January 2006. Postoperative pain score, need for narcotics, and adverse events were recorded. The On-Q catheter is inserted intraoperatively through the lateral lower eyelid into the muscle cone under direct visualization, prior to the orbital implant placement. The On-Q system continually infuses anesthesia (bupivacaine) to the retrobulbar site for 5 days.', 'Among 20 patients, mean postoperative period pain score, with On-Q in place, was 1.3 (scale of 0 to 10). Nine patients (45%) did not need any adjunctive oral narcotics. Two patients experienced postoperative nausea. One catheter connector leaked, thereby decreasing delivery of retrobulbar anesthetic resulting a pain level of 6, the highest level in the study. There were no postoperative infections. No systemic toxic effects from bupivacaine were observed clinically.",
            "output": [
                "Do on-Q pump for pain control after orbital implant surgery?"
            ]
        },
        {
            "id": "task847-7d83adda76624c6fbff84babf389e866",
            "input": "Non-muscle myosin II (NM II) regulates a wide range of cellular functions, including neuronal differentiation, which requires precise spatio-temporal activation of Rho GTPases. The molecular mechanism underlying the NM II-mediated activation of Rho GTPases is poorly understood. The present study explored the possibility that NM II regulates neuronal differentiation, particularly morphological changes in growth cones and the distal axon, through guanine nucleotide exchange factors (GEFs) of the Dbl family.', 'NM II colocalized with GEFs, such as \u03b2PIX, kalirin and intersectin, in growth cones. Inactivation of NM II by blebbistatin (BBS) led to the increased formation of short and thick filopodial actin structures at the periphery of growth cones. In line with these observations, FRET analysis revealed enhanced Cdc42 activity in BBS-treated growth cones. BBS treatment also induced aberrant targeting of various GEFs to the distal axon where GEFs were seldom observed under physiological conditions. As a result, numerous protrusions and branches were generated on the shaft of the distal axon. The disruption of the NM II-GEF interactions by overexpression of the DH domains of \u03b2PIX or Tiam1, or by \u03b2PIX depletion with specific siRNAs inhibited growth cone formation and induced slender axons concomitant with multiple branches in cultured hippocampal neurons. Finally, stimulation with nerve growth factor induced transient dissociation of the NM II-GEF complex, which was closely correlated with the kinetics of Cdc42 and Rac1 activation.",
            "output": [
                "Does non-muscle myosin II regulate neuronal actin dynamics by interacting with guanine nucleotide exchange factors?"
            ]
        },
        {
            "id": "task847-3987300e175a4e88ae6850b711cf9ac7",
            "input": "Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines.', 'We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell (LO2 cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation.', 'Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and LO2 cell line (p<0.05). Compared with the LO2 cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05).",
            "output": [
                "Does talin-1 correlate with reduced invasion and migration in human hepatocellular carcinoma cells?"
            ]
        },
        {
            "id": "task847-b0746af8a19147588ae13457e9bffb92",
            "input": "Distension of the ischemic region has been related to an increased incidence of spontaneous ventricular arrhythmias following coronary occlusion. This study analyzed whether regional ischemic distension predicts increased ventricular fibrillation inducibility after coronary occlusion in swine.', 'In 18 anesthetized, open-chest pigs, the left anterior descending coronary artery was ligated for 60 min. Myocardial segment length in the ischemic region was monitored by means of ultrasonic crystals. Programmed stimulation was applied at baseline and then continuously between 10 and 60 min after coronary occlusion.', 'Coronary occlusion induced a rapid increase in end-diastolic length in the ischemic region, which reached 109.4% (0.9%) of baseline values 10 min after occlusion (P<.001). On average, 6.6 (0.5) stimulation protocols were completed and 5.4 (0.6) ventricular fibrillation episodes induced between 10 and 60 min of coronary occlusion. Neither baseline serum potassium levels nor the size of the ischemic region were significantly related to ventricular fibrillation inducibility. In contrast, the increase in end-diastolic length 10 min after coronary occlusion was associated directly (r=0.67; P=.002) with the number of induced ventricular fibrillation episodes and inversely (r=-0.55; P=.018) with the number of extrastimuli needed for ventricular fibrillation induction.",
            "output": [
                "Does distension of the ischemic region predict increased ventricular fibrillation inducibility following coronary occlusion in swine?"
            ]
        },
        {
            "id": "task847-d8402560b7504915868ba86ffb46b0dd",
            "input": "In children, excessive ingestion of fluoride from different sources including bottled drinking water and flavoured beverages or soft drinks can lead to the development of dental fluorosis. In addition, the pH level of beverages is important. Low pH can cause dental erosion. In this study we explore the fluoride content and pH level of certain popular beverages available in Malaysian supermarkets and hawkers' stalls.\", \"Bottled drinking water and selected popular flavoured packet drinks were purchased from a supermarket and the corresponding flavoured hawkers' drinks, from a hawker's stall in Kuala Lumpur. Fluoride and pH of the beverages were determined using digital fluoride meter and digital pH meter respectively.\", \"It was found that fluoride content and pH level vary among the beverages. The mean fluoride content in both packet and hawkers' drinks (7.64\u00b11.88 mg/L, 7.51\u00b11.60 mg/L, respectively) was approximately 7 times higher than the bottled drinking water (1.05\u00b10.35 mg/L). Among the beverages, the tea packet drink was found to contain the highest amount of fluoride (13.02\u00b10.23 mg/L). The mean pH of bottled-drinking water was near neutral (6.96\u00b10.17), but acidic for both supermarket (4.78.00\u00b10.49) and hawkers' drinks (5.73\u00b10.24). The lychee packet drink had the lowest pH level (2.97\u00b10.03).",
            "output": [
                "Do high fluoride and low pH level have been detected in popular flavoured beverages in Malaysia?"
            ]
        },
        {
            "id": "task847-b42c527473ba40f28474db9b93631a2a",
            "input": "There is a need for improved predictability in cataract surgery. The aim of this study was to investigate whether implantation of intraocular lenses (IOLs) with accurately labeled dioptric power could improve the postoperative results and allow better predictability.', '113 eyes were implanted with Crystal Evolution\u00ae (MTO) IOLs and 261 eyes with AF-1 iMics1\u00ae (Hoya) IOLs. The predictability of the postoperative spherical equivalence (SE) and the best-corrected visual acuity (BCVA) were compared between both groups. The predictability was also compared to 2 previous studies.', 'With Crystal Evolution\u00ae, the predictability was significantly better than with AF-1 iMics1\u00ae (p<0.0001). The results were also better than those described in the 2 studies. Although the BCVA obtained with Crystal Evolution\u00ae were better than with AF-1 iMics1\u00ae, the difference were not significant.",
            "output": [
                "Does a new IOL with labeled accurate dioptric powers reduce the postoperative refractive error?"
            ]
        },
        {
            "id": "task847-a56ffd02773543ceb355c41a0f0ce7a4",
            "input": "To determine whether the responses of elders compared with younger patients differed significantly on a structured dizziness case history.', 'Retrospective case reviews.', 'Outpatient balance function testing center.', 'Two-hundred thirty-three adults who underwent vestibular function testing and completed a structured case history. The mean age of the adult group (18-64 yr) was 46.4 years. The mean age of the old adult group (65 yr and older) was 76.2 years.', \"Patient's self-reported symptoms on a structured case history questionnaire.\", 'Younger adults reported significantly more complaints of true vertigo and associated nausea and vomiting compared with older patients. Older patients tended to report symptoms of unsteadiness or falling. Despite the lack of vertiginous symptoms, BPPV was common in older adults.",
            "output": [
                "Do self-report symptoms differ between younger and older dizzy patients?"
            ]
        },
        {
            "id": "task847-12f477bafffb4289910461c0e399c87e",
            "input": "Physical performances and cognition are positively related in cognitively healthy people. The aim of this study was to examine whether physical performances are related to specific cognitive functioning in older people with mild to severe cognitive impairment.', 'This cross-sectional study included 134 people with a mild to severe cognitive impairment (mean age 82 years). Multiple linear regression was performed, after controlling for covariates and the level of global cognition, with the performances on mobility, strength, aerobic fitness, and balance as predictors and working memory and episodic memory as dependent variables.', 'The full models explain 49-57% of the variance in working memory and 40-43% of episodic memory. Strength, aerobic fitness, and balance are significantly associated with working memory, explaining 3-7% of its variance, irrespective of the severity of the cognitive impairment. Physical performance is not related to episodic memory in older people with mild to severe cognitive impairment.",
            "output": [
                "Is physical performance associated with working memory in older people with mild to severe cognitive impairment?"
            ]
        },
        {
            "id": "task847-0027b891b17543a79767a0f5e048d46c",
            "input": "Limited knowledge exists about the value of tumor size in surgically treated cervical cancer (CX) using a tumor size of 2 cm as cut-off value.', 'A total of 366 cases of CX FIGO stage IB who received upfront surgery were evaluated regarding tumor size, the prediction of pelvic lymph node involvement, and recurrence-free and overall survival during a median follow-up time of 94 months. Tumors \u22642.0 cm were defined as small, tumors 2.1-4.0 cm as medium sized and those larger than 4 cm as bulky disease.', 'Small tumors were seen in 28.7%, medium sized in 52.5% and bulky tumors in 18.9%. There was a significant higher frequency of pelvic lymph node involvement with increasing tumor size (13.3% vs. 23.4% vs. 43.5%, respectively; p<0.001) and an increase of recurrent disease (6.7% vs. 18.8% vs. 29.4%, respectively; p<0.001). The 5-year overall survival rate was significantly reduced with increasing tumor size (94.0% vs. 85.1% vs. 69.9%, respectively; p<0.001). Pelvic lymph node involvement and maximal tumor size were independent prognostic factors for both recurrence-free and overall survival in multivariate analysis.",
            "output": [
                "Is a cut-off value of 2 cm in tumor size of prognostic value in surgically treated FIGO stage IB cervical cancer?"
            ]
        },
        {
            "id": "task847-4c81168e098e4c1c9209d13645a78764",
            "input": "Anxiety and depression frequently co-occur in the elderly and in patients with dementia. Prior research has shown that depression is related to the risk of dementia, but the effect of anxiety on dementia remains unclear. We studied whether anxiety symptoms and anxiety disorders are associated with the risk of dementia and cognition.', 'We studied 2,708 nondemented participants from the prospective, population-based Rotterdam Study who underwent the Hospital Anxiety and Depression Scale (HADS) (sample I, baseline 1993-1995) and 3,069 nondemented participants who underwent screening for anxiety disorders (sample II, baseline 2002-2004). In 1993-1995, anxiety symptoms were assessed using the HADS. In 2002-2004, anxiety disorders were assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. In both study samples, participants were continuously monitored for dementia until January 1, 2011. Cognition was tested in 2002-2004 and at a follow-up visit in 2009-2011 in sample II only.', 'In sample I, 358 persons developed dementia, and in sample II, 248 persons developed dementia. We did not find an association with the risk of dementia for anxiety symptoms (hazard ratio 1.05, 95% confidence interval: 0.77-1.43, Wald statistic 0.08, p\\xa0= 0.77, df\\xa0= 1) or for anxiety disorders (hazard ratio 0.92, 95% confidence interval: 0.58-1.45, Wald statistic 0.14, p\\xa0= 0.71, df\\xa0= 1). We could demonstrate an association of anxiety disorders with poor cognition cross-sectionally, but this attenuated after additional adjustments.",
            "output": [
                "Is anxiety associated with the risk of dementia or cognitive decline : the Rotterdam Study?"
            ]
        },
        {
            "id": "task847-b78e9f1caf8f446cb1b38820bcbdadbe",
            "input": "The CXC chemokine, CXCL12, and its receptor, CXCR4 promote metastases of a variety of solid tumors, including non-small cell lung cancer (NSCLC). The expression of CXCR4 on tumor cells may represent a critical biomarker for their propensity to metastasize. This study was performed to evaluate the hypothesis that co-expression of pan-cytokeratin and CXCR4 may be a prognostic marker for patients with advanced NSCLC.', 'We evaluated CXCR4 levels on circulating pan-cytokeratin positive cells from patients with NSCLC. NSCLC tumor and metastases were also assessed for the presence of CXCR4.', 'Pan-cytokeratin positive cells were increased in the circulation of patients with NSCLC, as compared to normal control subjects. Patients with pan-cytokeratin +/CXCR4+ = 2,500 cells/ml had a significant improvement in median survival when compared with patients with pan-cytokeratin +/CXCR4+ >2,500 cells/ml (not achieved versus 14 weeks). CXCR4 expression was found on NSCLC tumors and at sites of tumor metastasis.",
            "output": [
                "Is cXCR4 expression on circulating pan-cytokeratin positive cells associated with survival in patients with advanced non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-9f92df6365ad43e6a85718ff88a116da",
            "input": "Lead, an example of heavy metals, has, for decades, being known for its adverse effects on various body organs and systems such that their functions are compromised.', 'In the present study, the ability of lead to adversely affect the male reproductive system was investigated and tomato (Lycopersicon esculentum: Source of antioxidants) paste (TP) was administered orally to prevent the adverse effects of Pb.', 'Fifteen Sprague Dawley rats, randomised into three groups (n = 5), were used for this study. Animals in Group A served as the control and were drinking distilled water. Animals in Groups B and C were drinking 1% Pb (II) acetate (LA). Group C animals were, in addition to drinking LA, treated with 1.5 ml of TP/day. All treatments were for 8 weeks.', 'A Mann-Whitney U-test was used to analyse the results obtained.', 'The obtained results showed that Pb caused a significant reduction in the testicular weight, sperm count, life-death ratio, sperm motility, normal sperm morphology, and plasma and tissue superoxide dismutase and catalase activity, but a significant increase in plasma and tissue malondialdehyde concentration. But, Pb did not cause any significant change in the serum testosterone level. TP, however, significantly reduced these adverse effects of Pb.",
            "output": [
                "Does tomato ( Lycopersicon esculentum ) prevent lead-induced testicular toxicity?"
            ]
        },
        {
            "id": "task847-74e163899f604ef5930876f4645f1ed2",
            "input": "The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage.', 'Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized.",
            "output": [
                "Does dll1 haploinsufficiency in adult mice lead to a complex phenotype affecting metabolic and immunological processes?"
            ]
        },
        {
            "id": "task847-7965df565a684006b4fa7c5ac0a36364",
            "input": "Severe and potentially fatal hypersensitivity reactions to drugs, particularly antiepileptics, are clinically unpredictable. Recent evidence has revealed a strong and specific association between the implicated drug, the type of adverse reaction, and the particular HLA genotype. An urgent need exists for rapid diagnosis of HLA status to guide drug prescription; however, traditional HLA genotyping has a long turnaround time, is expensive, and is available only in specialized centers. We tested the feasibility of the loop-mediated isothermal amplification (LAMP)-based approach to detect a specific HLA genotype. As an example, we used B*1502, an HLA allele strongly associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, and validated the assay's application as a simple, accurate, rapid, and low-cost blood test for use in both clinical and bedside settings.\", 'We evaluated B*1502 status with the new LAMP method and compared the results with those obtained by sequence-based typing (SBT) (n = 250) and by sequence-specific primer PCR (SSP-PCR) (n = 200) for 450 samples of DNA (n = 50) and blood (n = 400) from a hematology laboratory.', 'LAMP results showed 100% concordance with both SBT and SSP-PCR results, confirming that LAMP detection of a specific HLA genotype (B*1502 in this case) is an accurate method. All results were available within 1 h.",
            "output": [
                "Does new testing approach in HLA genotyping help overcome barriers in effective clinical practice?"
            ]
        },
        {
            "id": "task847-7e6c935f29a64f95b052d4ef05b87120",
            "input": "The onset and offset of weak low-frequency magnetic fields triggered evoked potentials in human subjects that could be detected using nonlinear analysis, but not by means of time averaging. Because the magnetic fields and their induced electric fields were both present in the brain, their respective role in producing the effect on brain activity could not be ascertained. We inquired whether a biophysical coupling mechanism involving only the electric field could explain the occurrence of the brain potentials.', 'An external electric field capable of producing a brain electric field comparable to that induced by the magnetic stimuli was identified by finite-element analysis. The electroencephalogram from 23 subjects was measured from six scalp derivations in the presence and absence of the external electric field, and the presence of evoked potentials was assessed using nonlinear and linear analyses.', 'Evoked potentials were observed in all but one subject (p < 0.05 in each subject); the potentials had the same latency, duration, and distribution of magnitudes as seen in the earlier studies, and were detectable only by means of nonlinear analysis. Using a realistic physical model of an ion channel, we showed that transduction of an electric field could be explained by assuming that the field exerted a force on glycocalyx molecules attached to a channel gate.",
            "output": [
                "Is the electric field a sufficient physical determinant of the human magnetic sense?"
            ]
        },
        {
            "id": "task847-bd8ce07f29304e4985a983f0b1ca16f0",
            "input": "Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity.', 'We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active.', 'The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models.', 'We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals.",
            "output": [
                "Does physical activity attenuate the body mass index-increasing influence of genetic variation in the FTO gene?"
            ]
        },
        {
            "id": "task847-a80f7db5e6b8450696f9dd502a056878",
            "input": "Ingested proteins are known to stimulate a rise in insulin and glucagon concentrations. In our effort to explain this effect, we have begun to measure the effect of individual amino acids.', 'The objectives were to determine the effect of lysine ingestion on insulin and glucagon concentrations and whether the effect is moderated by glucose ingestion.', 'Thirteen healthy subjects were studied on 4 occasions. Water, 25 g glucose, 1 mmol lysine/kg lean body mass, or lysine plus glucose was given on separate occasions at 0800 after a 12-h fast. Serum lysine, glucose, insulin, and glucagon were measured during a 2.5-h period. The amount of lysine provided was equivalent to that present in a 672-g (24-oz) steak.', 'Lysine ingestion resulted in an approximately 3-fold increase in lysine concentration and in a small decrease in glucose concentration. When lysine was ingested with glucose, the 2.5-h glucose area response decreased by 44% (P < 0.02). Lysine alone increased the insulin area response modestly; the insulin increase when lysine was ingested with glucose was similar to that when only glucose was ingested. Lysine stimulated an increase in glucagon (P < 0.02), whereas glucose decreased glucagon.",
            "output": [
                "Does lysine ingestion markedly attenuate the glucose response to ingested glucose without a change in insulin response?"
            ]
        },
        {
            "id": "task847-c1d8c707b92646379c04ec2589e41e56",
            "input": "A relation between birth weight and adult body composition has been reported in singleton populations, especially when more accurate measures of body composition, such as dual-energy X-ray absorptiometry (DXA) were used. It remains uncertain whether this is mediated by a direct effect of fetal nutrition, through factors in the shared environment, or through genetic factors.', 'The objective was to investigate the relation between birth weight and body composition with the use of a co-twin design.', 'DXA measurements and birth weights were available for 2228 dizygotic and 842 monozygotic female twins aged between 18 and 80 y. Multivariate regression models were used to identify both individual specific relations and those mediated through the shared environment.', 'Significant relations were found between birth weight and DXA measures for individuals. A 1-kg increase in birth weight was associated with a 1.72-kg increase in lean mass, a 0.25-kg increase in fat mass, and a 0.05-unit increase in the lean:fat mass ratio. Within twin pairs, the analysis showed that associations between birth weight and absolute levels of lean and fat mass were mediated through individual-specific effects, whereas the relation between birth weight and the proportion of lean to fat mass was mediated purely through factors common to twin pairs.",
            "output": [
                "Is an obesogenic postnatal environment more important than the fetal environment for the development of adult adiposity : a study of female twins?"
            ]
        },
        {
            "id": "task847-2c9372bf1c884f08995ebb9fabef344f",
            "input": "To investigate the effect of a yearlong moderate-intensity aerobic exercise intervention on C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) among overweight or obese postmenopausal women.', 'In a randomized controlled trial, 115 postmenopausal, overweight or obese, sedentary women, aged 50-75 yr were randomized to an aerobic exercise intervention of moderate-intensity (60%-75% observed maximal HR), for > or = 45 min x d(-1), 5 d x wk (n = 53), or to a 1-d x wk(-1) stretching control (n = 62), on an intent-to-treat basis. CRP, SAA, and IL-6 were measured at baseline, at 3 months, and at 12 months.', 'From baseline to 12 months, CRP decreased 10% in exercisers and increased 12% in controls (P = 0.01); no effects were observed for SAA and IL-6. Among participants at baseline who were obese (body mass index (BMI) > or = 30 kg x m(-2)) or had abdominal obesity (waist circumference (WC) > or = 88 cm), exercise resulted in a more pronounced reduction in CRP (BMI > or = 30 kg x m(-2), P = 0.002; WC > or = 88 cm, P < 0.0001), borderline for SAA (BMI > or = 30 kg x m(-2), P = 0.08; WC > or = 88 cm, P = 0.04); no intervention effects were observed among women who did not have these characteristics. Overall, weight loss was minimal in the exercise intervention ( approximately 1.8 kg). Linear trends were observed between CRP and 12-month changes in aerobic fitness (Ptrend = 0.006), exercise adherence (Ptrend = 0.004), percentage body fat (Ptrend = 0.002), body weight (Ptrend = 0.002), WC (Ptrend = 0.02), and intra-abdominal fat (Ptrend = 0.03).",
            "output": [
                "Does a yearlong exercise intervention decrease CRP among obese postmenopausal women?"
            ]
        },
        {
            "id": "task847-b0ea5d5ef10f428dbf262273d47c4e83",
            "input": "The oral cavity has been considered a potential reservoir for Helicobacter pylori (H pylori) , from where the organism causes recurrent gastric infections.', 'With this case-control study we tried to evaluate the role of H pylori in the etiology of mucosal inflammation, a condition that compounds the morbid state associated with oral submucous fibrosis (OSF).', 'Subjects ( n = 150) were selected following institutional regulations on sample collection and grouped into test cases and positive and negative controls based on the presence of mucosal fibrosis and inflammation. The negative controls had none of the clinical signs. All patients underwent an oral examination as well as tests to assess oral hygiene/periodontal disease status; a rapid urease test (RUT) of plaque samples was also done to estimate the H pylori bacterial load. We used univariate and mutivariate logistic regression for statistical analysis of the data and calculated the odds ratios to assess the risk posed by the different variables.', 'The RUT results differed significantly between the groups, reflecting the variations in the bacterial loads in each category. The test was positive in 52% in the positive controls (where nonspecific inflammation of oral mucosa was seen unassociated with fibrosis), in 46% of the test cases, and in 18% of the negative controls (healthy volunteers) (chi2 = 13.887; P < 0.01). A positive correlation was seen between the oral hygiene/periodontal disease indices and RUT reactivity in all the three groups.",
            "output": [
                "Is helicobacter pylori coinfection a confounder , modulating mucosal inflammation in oral submucous fibrosis?"
            ]
        },
        {
            "id": "task847-1e42122bb8a442eca99b4351de39e88a",
            "input": "Two recent genome-wide association studies identified the liver expressed transmembrane protein adiponutrin to be associated with liver related phenotypes such as non-alcoholic fatty liver disease and liver function enzymes. These associations were not uniformly reported for various ethnicities. The aim of this study was to investigate a common non-synonymous variant within adiponutrin (rs738409, exon 3) with parameters of liver function in three independent West Eurasian study populations including a total of 4290 participants.', 'The study was performed in (1) the population based Bruneck Study (n=783), (2) the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk Study from Austria based on a healthy working population (n=1705), and the Utah Obesity Case-Control Study including a group of 1019 severely obese individuals (average body mass index 46.0 kg/m(2)) and 783 controls from the same geographical region of Utah. Liver enzymes measured were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT).', 'A strong recessive association of this polymorphism was found with age and gender adjusted ALT and AST concentrations: being homozygous for the minor allele resulted in a highly significant increase of ALT concentration of 3.53 U/l (p=1.86 x 10(-9)) and of AST concentration of 2.07 U/l (p=9.58 x 10(-6)), respectively. The associations were consistently found in all three study populations.",
            "output": [
                "Does a common variant in the adiponutrin gene influence liver enzyme values?"
            ]
        },
        {
            "id": "task847-dc05a6f080d24d698c9ce77bb718cf41",
            "input": "To assess the association between the intake of dietary fibre and carotid intima-media thickness (IMT) in a Mediterranean population at high cardiovascular risk.', 'Baseline cross-sectional assessment of 457 men and women (average age 67 years) from two different Spanish centres of the PREDIMED trial. A previously validated food frequency questionnaire (137 food items) was administered by trained dieticians in a face-to-face interview. Mean common carotid IMT was measured using B-mode ultrasound imaging of the right and left carotid arteries by four certified sonographers who used a common protocol. Anthropometric and blood pressure measurements were performed and samples of fasting blood were obtained. Participants were categorized into four groups (roughly quartiles: < or =21; >21 to < or =25; >25 to < or =31 and >31 g/day) of energy-adjusted intake of dietary fibre. Multiple linear regression models were used to adjust for age, sex, centre, smoking, body mass index, diabetes, blood pressure, lipid levels and statin use.', 'In the crude analyses, energy-adjusted fibre intake showed a significant inverse correlation with IMT (r=-0.27, P<0.001). In multivariate analyses, a modest, though statistically significant (P=0.03) inverse association between energy-adjusted fibre intake and IMT was also found. The multivariate-adjusted difference in average IMT was -0.051 mm (95% confidence interval: -0.094 to-0.009, P=0.02) for participants whose intake was >35 g/day, (n=47) when compared with those whose intake was <25 g/day (n=224).",
            "output": [
                "Is dietary fibre intake inversely associated with carotid intima-media thickness : a cross-sectional assessment in the PREDIMED study?"
            ]
        },
        {
            "id": "task847-9a8134cc668c4ee1b81e7f650cb83f06",
            "input": "To identify and characterize adhesion-associated proteins in the potential probiotic Lactobacillus fermentum BCS87.', 'Protein suspensions obtained from the treatment of Lact. fermentum BCS87 with 1 mol 1(-1) LiCl were analysed by Western blotting using HRP-labelled porcine mucus and mucin. Two adhesion-associated proteins with relative molecular weight of 29 and 32 kDa were identified. The N-terminal and internal peptides of the 32 kDa protein (32-Mmubp) were sequenced, and the corresponding gene (32-mmub) was found by inverse polymerase chain reaction. The complete nucleotide sequence of 32-mmub revealed an open reading frame of 903 bp encoding a primary protein of 300 amino acids and a mature protein of 272 residues. A basic local alignment search showed 47-99% identity to solute-binding components of ATP binding cassette transporter proteins in Lactobacillus, Streptococcus and Clostridium. An OpuAC-conserved domain was identified and phylogenetic relationship analysis confirmed that 32-Mmubp belongs to the OpuAC family.",
            "output": [
                "Does lactobacillus fermentum BCS87 express mucus- and mucin-binding proteins on the cell surface?"
            ]
        },
        {
            "id": "task847-b1ce1bc9a51842a6916ce861400824c3",
            "input": "Islets from adult rat possess weak antioxidant defense leading to unbalance between superoxide dismutase (SOD) and hydrogen peroxide-inactivating enzymatic activities, catalase (CAT) and glutathione peroxidase (GPX) rending them susceptible to oxidative stress. We have shown that this vulnerability is influenced by maternal diet during gestation and lactation.', 'The present study investigated if low antioxidant activity in islets is already observed at birth and if maternal protein restriction influences the development of islet antioxidant defenses. Rats were fed a control diet (C group) or a low protein diet during gestation (LP) or until weaning (LPT), after which offspring received the control diet. We found that antioxidant enzymatic activities varied with age. At birth and after weaning, normal islets possessed an efficient GPX activity. However, the antioxidant capacity decreased thereafter increasing the potential vulnerability to oxidative stress. Maternal protein malnutrition changed the antioxidant enzymatic activities in islets of the progeny. At 3 months, SOD activity was increased in LP and LPT islets with no concomitant activation of CAT and GPX. This unbalance could lead to higher hydrogen peroxide production, which may concur to oxidative stress causing defective insulin gene expression due to modification of critical factors that modulate the insulin promoter. We found indeed that insulin mRNA level was reduced in both groups of malnourished offspring compared to controls. Analyzing the expression of such critical factors, we found that c-Myc expression was strongly increased in islets from both protein-restricted groups compared to controls.",
            "output": [
                "Does early low protein diet aggravate unbalance between antioxidant enzymes leading to islet dysfunction?"
            ]
        },
        {
            "id": "task847-c946ec859e6f4900b60c12d1142f10fe",
            "input": "This study examined the predictive factors of preference for residential care in cognitively intact and impaired elders and their family caregivers. It was hypothesized that disagreement in preference for residential care between the elders and their caregivers was greater in the cognitively impaired.', 'A cross-sectional survey was conducted during June 2007 to March 2008 in Hong Kong, and 707 community-dwelling elders aged 65 and above and 705 family caregivers were interviewed. Cognitively impaired elders were over-sampled to give reliable estimates for that sub-group. A structural questionnaire was used to collect data on preference for residential care and potential factors. Logistic regression was used to identify the predictors.', \"More cognitively impaired elder-caregiver dyads (37.4%) had disagreement in preference for residential care than cognitively intact elder-caregiver dyads (20.5%) (p < .001). From the elders' perspective, less preference for residential care was associated with cognitive impairment, whereas greater preference was associated with depression (for cognitively intact elders), more usage of community service and functional impairment. From the caregivers' perspective, greater preference for residential care was associated with greater caregiver burden, or care-recipients having cognitive or functional impairment, or more usage of community services.",
            "output": [
                "Is disagreement in preference for residential care between family caregivers and elders greater among cognitively impaired elders group than cognitively intact elders group?"
            ]
        },
        {
            "id": "task847-3ca74723953b4bd38e4071dc4e3f52da",
            "input": "The epidermal growth factor receptor HER2 is overexpressed or amplified in 25%-30% of patients with breast cancer. The mechanism behind HER2 amplification is unknown, but may be a patho-physiological phenomenon caused by continuous stimulation and activation of the HER1-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation.', 'Tissue samples from malignant and adjacent normal breast tissue (autologous reference tissue) were collected from 118 women consecutively admitted for surgical treatment of breast cancer. In addition, 26 samples of normal breast tissue were collected from healthy women having breast reduction surgery. The tissue samples were homogenized and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method.', 'HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8 x 10(-6)), while HER2 (p<10(-7)) and HER3 (p=3 x 10(-5)) were up regulated. Comparing autologous reference tissue with normal tissue showed down regulation of HER1 (p=0.122) and up regulation of HER2 (p=10(-6)), HER3 (p<10(-7)) and HER4 (p<10(-7)). Furthermore, we observed that correlations between the receptor combinations HER1-2, HER1-3 and HER1-4 were maintained from normal breast tissue to autologous reference breast tissue, but were lost in cancer tissue.",
            "output": [
                "Are hER1-4 protein concentrations in normal breast tissue from breast cancer patients expressed by the same profile as in the malignant tissue?"
            ]
        },
        {
            "id": "task847-a7a9f6cf912c4f75a28101268e715e4d",
            "input": "The prevalence of interstitial cystitis (IC) in young women, especially in those 18 years old or younger, is not well defined. This case series was performed to investigate IC as a cause of chronic pelvic pain (CPP) in young women.', 'Case series.', 'University medical center.', 'Twenty-eight women with CPP, ages 13 to 25, who underwent concomitant laparoscopy and cystoscopy.', 'All subjects underwent concomitant diagnostic laparoscopy and cystoscopy with hydrodistension for evaluation of CPP. Charts were reviewed to discern preoperative symptoms, operative findings, and postoperative diagnoses.', 'Diagnosis of IC based on symptoms and cystoscopic findings.', 'All 28 women had CPP, 23 (82%) had dysmenorrhea, and 12 of 25 (48%) sexually active subjects had dyspareunia. Twenty-six subjects (93%) had urinary symptoms including frequency (75%), nocturia (32%), urgency (25%), and dysuria (18%). Eleven (39%) subjects were diagnosed with IC and 18 (64%) with endometriosis, including 7 (25%) subjects with both IC and endometriosis. Laparoscopic findings were normal in 6 (21%) subjects. Of the 26 subjects with urinary symptoms, 21 (81%) had findings on laparoscopy or cystoscopy. In this cohort of young women with chronic pelvic pain, urinary frequency and dyspareunia were significantly associated with the diagnosis of IC.",
            "output": [
                "Is interstitial cystitis an etiology of chronic pelvic pain in young women?"
            ]
        },
        {
            "id": "task847-c77d6479019742d89e90eec5510132bc",
            "input": "Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (H&E) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.', 'Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed H&E alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.', \"Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using H&E diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for H&E/p16/Ki-67 combined were comparable to that of H&E alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, H&E/p16/Ki-67 combined, and H&E alone.",
            "output": [
                "Does p16 improve interobserver agreement in diagnosis of anal intraepithelial neoplasia?"
            ]
        },
        {
            "id": "task847-57f3007bc85e438584655ffc6094a466",
            "input": "rs1333049 polymorphism on chromosome 9p21 has been shown to affect susceptibility to coronary artery disease (CAD) in Caucasians. This study examined the association of rs1333049 with myocardial infarction (MI), angiographic severity of CAD and clinical outcome after a first acute MI in Han Chinese.', 'rs1333049 polymorphism was genotyped in 520 patients with a first acute MI and in 560 controls. The number of angiographically documented diseased coronary arteries (luminal diameter stenosis > or = 50%), echocardiographic left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACE) during follow-up (mean, 29+/-15 months) were recorded.', 'Patients with MI had higher frequencies of the CC genotype (30.0% vs. 20.7%) or C allele (55.5% vs. 46.2%) compared with controls (all p<0.01). rs1333049 polymorphism was strongly associated with MI [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.22-1.79] after adjusting for traditional risk factors. Although longer hospitalization stay was observed in patients with the rs1333049-C allele, this polymorphism was not related to angiographic severity of CAD, LVEF, and occurrence of MACE after MI.",
            "output": [
                "Is chromosome 9p21 polymorphism associated with myocardial infarction but not with clinical outcome in Han Chinese?"
            ]
        },
        {
            "id": "task847-e9d062edaa0c426aaf05ee173a4d7a1e",
            "input": "Kawasaki disease (KD) is a multisystem vasculitis affecting children and is characterized by immune activation in the acute stage of disease. Systemic inflammation eventually subsides, although coronary arteritis persists, resulting in aneurysm formation. KD is the leading cause of acquired heart disease among children in North America. Accepted treatment guidelines include high-dose intravenous immunoglobulin (IVIG) and aspirin in the acute phase. Although this therapy is effective, the cellular and molecular mechanisms involved are not clear. The aim of this study was to examine the effect of IVIG and salicylate at each stage of disease development.', 'Using a murine model of KD, we established and validated several in vitro techniques to reflect 3 key steps involved in disease pathogenesis, as follows: thymidine incorporation to evaluate T cell activation, enzyme-linked immunosorbent assay to measure tumor necrosis factor alpha (TNFalpha) production, and real-time polymerase chain reaction to examine TNFalpha-mediated expression of matrix metalloproteinase 9 (MMP-9).', 'At therapeutic concentrations, IVIG, but not salicylate, effectively reduced the immune response leading to TNFalpha expression. Unexpectedly, pharmacologic doses of salicylate were not able to inhibit TNFalpha production and in fact enhanced its production. Neither drug directly regulated MMP-9 expression but did so only indirectly via modulating TNFalpha. TNFalpha activity was a prerequisite for local expression of MMP-9 at the coronary artery.",
            "output": [
                "Do intravenous immunoglobulin and salicylate differentially modulate pathogenic processes leading to vascular damage in a model of Kawasaki disease?"
            ]
        },
        {
            "id": "task847-4bf689eb63d04874861391772cd8400e",
            "input": "The ANP32A gene encodes a tumor suppressor molecule that plays a regulatory role in apoptosis and interferes with canonical Wnt signaling in vitro. We undertook this study to test whether genetic variation at ANP32A was associated with osteoarthritis (OA) in women.', 'Single-nucleotide polymorphisms (SNPs) in the ANP32A gene were genotyped in 438 control women, 425 women with total knee replacements (TKRs), and 537 women with total hip replacements (THRs) from the Nottingham case-control study as well as in 820 women from the population-based Chingford Study cohort for whom hip and knee radiographs were available. The most highly associated SNP was further tested in women from the Rotterdam Study (131 with THRs, 633 with knee OA, and 1,567 controls) and the TwinsUK Study cohort (67 with THRs, 43 with TKRs, and 358 controls), for a total of 2,170 patients with OA and 2,849 controls.', 'The ANP32A transcript was abundantly expressed in normal and OA articular cartilage. Three SNPs in the ANP32A gene were significantly associated in Nottingham patients with hip OA, but not knee OA. One of these (rs7164503) was associated with hip and knee OA in the Chingford Study cohort and with THR in the TwinsUK Study cohort, but the association was not statistically significant in the Rotterdam Study. When we combined hip data from all 4 cohorts, we found that the minor allele of rs7164503 was associated with a significantly lower risk of hip OA (Mantel-Haenszel odds ratio 0.67 [95% confidence interval 0.53-0.84], P < 3.8 x 10(-4)) and that a similar trend was observed for knee OA (Mantel-Haenszel odds ratio 0.87 [95% confidence interval 0.73-1.01], P < 0.055).",
            "output": [
                "Is variation at the ANP32A gene associated with risk of hip osteoarthritis in women?"
            ]
        },
        {
            "id": "task847-619bf5123eb941bcadaa15335629d064",
            "input": "We have previously identified in articular cartilage an abundant pool of the heparin-binding growth factor, fibroblast growth factor 2 (FGF-2), which is bound to the pericellular matrix heparan sulfate proteoglycan, perlecan. This pool of FGF-2 activates chondrocytes upon tissue loading and is released following mechanical injury. In vitro, FGF-2 suppresses interleukin-1-driven aggrecanase activity in human cartilage explants, suggesting a chondroprotective role in vivo. We undertook this study to investigate the in vivo role of FGF-2 in murine cartilage.', 'Basal characteristics of the articular cartilage of Fgf2(-/-) and Fgf2(+/+) mice were determined by histomorphometry, nanoindentation, and quantitative reverse transcriptase-polymerase chain reaction. The articular cartilage was graded histologically in aged mice as well as in mice in which osteoarthritis (OA) had been induced by surgical destabilization of the medial meniscus. RNA was extracted from the joints of Fgf2(-/-) and Fgf2(+/+) mice following surgery and quantitatively assessed for key regulatory molecules. The effect of subcutaneous administration of recombinant FGF-2 on OA progression was assessed in Fgf2(-/-) mice.', 'Fgf2(-/-) mice were morphologically indistinguishable from wild-type (WT) animals up to age 12 weeks; the cartilage thickness and proteoglycan staining were equivalent, as was the mechanical integrity of the matrix. However, Fgf2(-/-) mice exhibited accelerated spontaneous and surgically induced OA. Surgically induced OA in Fgf2(-/-) mice was suppressed to levels in WT mice by subcutaneous administration of recombinant FGF-2. Increased disease in Fgf2(-/-) mice was associated with increased expression of messenger RNA of Adamts5, the key murine aggrecanase.",
            "output": [
                "Is fibroblast growth factor 2 an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis?"
            ]
        },
        {
            "id": "task847-8b91f92041c64eefb3f503132902b328",
            "input": "Four serotonin-related genes including guanine nucleotide binding protein beta polypeptide 3 (GNB3), 5-hydroxytryptamine receptor 1A (HTR1A; serotonin receptor 1A), 5-hydroxytryptamine receptor 2A (HTR2A; serotonin receptor 2A), and solute carrier family 6 member 4 (SLC6A4; serotonin neurotransmitter transporter) have been suggested to be candidate genes for influencing antidepressant treatment outcome. The aim of this study was to explore whether interaction among these genes could contribute to the pharmacogenomics of short-term antidepressant response in a Taiwanese population with major depressive disorder (MDD).', 'Included in this study were 101 MDD patients who were treated with antidepressants, 35 of whom were rapid responders and 66 non-responders after 2weeks of treatment. We genotyped four single nucleotide polymorphisms (SNPs), including GNB3 rs5443 (C825T), HTR1A rs6295 (C-1019G), HTR2A rs6311 (T102C), and SLC6A4 rs25533, and employed the generalized multifactor dimensionality reduction (GMDR) method to investigate gene-gene interactions.', 'Single-locus analyses showed the GNB3 rs5443 polymorphism to be associated with short-term antidepressant treatment outcome (P-value=0.029). We did not correct for multiple testing in these multiple exploratory analyses. Finally, the GMDR approach identified a significant gene-gene interaction (P-value=0.025) involving GNB3 and HTR2A, as well as a significant 3-locus model (P-value=0.015) among GNB3, HTR2A, and SLC6A4.",
            "output": [
                "Does interaction of serotonin-related genes affect short-term antidepressant response in major depressive disorder?"
            ]
        },
        {
            "id": "task847-f385b77b2f1848b0b67c9dda2e3cbed7",
            "input": "Fusobacterium nucleatum, a commensal opportunistic oral bacterium, is capable of invading gingival epithelial cells, but the entrance into human primary oral fibroblast cells has not been documented. This study evaluated the ability of three strains of F. nucleatum (F. nucleatum ssp. nucleatum, F. nucleatum ssp. polymorphum, and F. nucleatum ssp. vincentii) to enter gingival fibroblasts (GFs) and periodontal ligament fibroblasts (PLFs).', 'GFs and PLFs were cocultured for various periods of time with different strains of F. nucleatum. Scanning and transmission electron microscopy, together with confocal laser scanning microscopy, were used to visualize the entrance and presence of bacteria in host cells. Flow cytometry was performed to compare the load of internalized bacteria in GFs and PLFs exposed for 3 and 5 hours to live F. nucleatum labeled with fluorescein isothiocyanate.', 'All three strains of F. nucleatum were found entering and located in the cytoplasm of GFs and PLFs after 1 hour of exposure. Flow cytometry tests revealed a significant increase in the fluorescent signal, compared to baseline, derived from bacteria internalized in fibroblasts exposed for 3 hours (P <0.001); a further increase was found at 5 hours. The greatest bacterial mass in exposed fibroblasts of both types was of F. nucleatum ssp. polymorphum; the smallest was of F. nucleatum ssp. vincentii. Although not statistically significant, PLFs had a higher bacterial load than corresponding GFs.",
            "output": [
                "Does fusobacterium nucleatum enter normal human oral fibroblasts in vitro?"
            ]
        },
        {
            "id": "task847-7750b9c2b29341e6b8c6c6194127f1a1",
            "input": "Several criteria for treatment response to interferon beta (IFNbeta) have been proposed, although there is no consensus among different investigators. Hence, the aim of this study was to investigate magnetic resonance imaging (MRI) and clinical predictors of response during the first 12 months of therapy.', 'This is a prospective and longitudinal study of relapsing-remitting multiple sclerosis (RRMS) patients treated with IFNbeta. Patients were classified based on the presence of new lesions on MRI, relapses, confirmed disability increase, or combinations of all these variables after 1 year of therapy. Regression analysis was performed in order to identify variables of response after a follow-up of 3 years.', 'We included 222 RRMS patients. The logistic model demonstrated that only the combination of new active lesions on MRI with the presence of relapses (OR 4.4; 95% CI 1.6-12.5) or disability progression (Odds Ratio (OR) 7.1; 95% Confidence Interval (CI) 1.6-33.9), or both (OR 6.5; 95% CI 1.9-23.4) achieved significant values to identify those patients with a poor outcome.",
            "output": [
                "Do measures in the first year of therapy predict the response to interferon beta in MS?"
            ]
        },
        {
            "id": "task847-42983aacfd6f49ad9377859dd743136f",
            "input": "Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of growth factors that have been implicated in skin patho-physiology. Although endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) appear to be involved in mitogenesis and chemotaxis in epidermal keratinocytes, the activation of eNOS and VEGF production induced by HB-EGF and its signaling mechanism remains undefined.', 'We examined possible signal transduction pathways by which HB-EGF leads to eNOS activation and VEGF production in human epidermal keratinocyte cell line (HaCaT cells).', 'The phosphorylation of epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK; p42/p44 MAPK), Akt and eNOS were examined by Western blotting analysis. VEGF production was determined by enzyme-linked immunosorbent assay. Various inhibitors were utilized to investigate the signaling mechanisms of eNOS activation and VEGF production.', 'HB-EGF-induced phosphorylation of EGFR with maximum phosphorylation at 1h. HB-EGF-induced phosphorylation of p42/p44 MAPK in a few minutes. It activated Akt with maximum phosphorylation at 1h and eNOS with maximum phosphorylation at 3h. The HB-EGF-induced eNOS activation was significantly blocked by the p42/p44 MAPK inhibitor U0126 and the phosphatidylinositol 3-kinase (P13K) inhibitor LY294002. HB-EGF increased VEGF production. The HB-EGF-induced VEGF production was blocked by U0126 and LY294002. Finally, the HB-EGF-induced activation of Akt and eNOS was suppressed by VEGF competitive antagonist, CBO-P11.",
            "output": [
                "Do hB-EGF-induced VEGF production and eNOS activation depend on both PI3 kinase and MAP kinase in HaCaT cells?"
            ]
        },
        {
            "id": "task847-00c7da1a2add4e9698d192774ababe1e",
            "input": "The aims of this study are to test the ability of stromal cells from murine spleen to support hematopoiesis, to define the tissue source of precursors that seed these hematopoietic niches, and to determine the type of cells produced.', 'Cloned isolates of murine spleen stroma have been developed that support hematopoiesis. Analysis has been investigated in terms of tissue source of progenitors. Type and number of cells produced were analyzed by flow cytometry.', 'Hematopoietic precursors that seed cocultures exist in spleen and bone marrow (BM), but not thymus. Cell production is highest if overlay cells are enriched for hematopoietic precursors. BM contains more precursors than spleen, but the cell types produced are different. Cocultures established from spleen maintain a high proportion of a distinct class of dendritic-like cells produced in only low numbers in BM cocultures. These reflect the immature myeloid dendritic cell (DC) produced continuously in long-term spleen cultures established previously in this laboratory. Stroma-conditioned medium alone does not support DC development, but does support early outgrowth of myelomonocytic cells from precursors in both spleen and BM.",
            "output": [
                "Do splenic stromal niches support hematopoiesis of dendritic-like cells from precursors in bone marrow and spleen?"
            ]
        },
        {
            "id": "task847-db25c03d5e544851851a78397e3a9f1e",
            "input": "Inflammation plays a central role in many neurodegenerative diseases, including Parkinson's, Alzheimer's, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. Microglia are the resident macrophages of the central nervous system and are the cells primarily responsible for the inflammatory component of these diseases.\", 'Using gene expression profiling, we compared the profile of the neurospecific microglial cell line BV-2 after LPS stimulation to that of a macrophage cell line (J774A.1) stimulated with LPS.', 'A set of 77 genes that were modulated only in microglial cells after LPS stimulation was identified. One gene of interest, Gng12, was investigated further to determine its ability to modify the inflammatory response. Specifically, Gng12 mRNA levels were transiently increased after LPS stimulation. In addition, overall levels of Gng12 mRNA after LPS stimulation were significantly higher in BV-2 cells as compared to macrophage cells.",
            "output": [
                "Is gng12 a novel negative regulator of LPS-induced inflammation in the microglial cell line BV-2?"
            ]
        },
        {
            "id": "task847-175480880193499bbd591a1eeee9a47c",
            "input": "We hypothesized that erythropoietin (EPO)-immersed gelatin hydrogel microspheres (GHM) injected into ischemic legs might continuously release a small amount of EPO to locally stimulate angiogenesis without unfavorable systemic effects.', 'EPO is a potent angiogenic factor, but its use for relieving ischemic organs is limited because of the untoward systemic erythrogenic effect and its short half-life in plasma.', 'The right femoral arteries of BALB/c mice were ligated. Recombinant human EPO (5,000 IU/kg)-immersed GHM was injected into the right hind limb muscles (n = 12); the control groups included a saline-injected group (n = 12), an EPO-injected group (n = 8), and an empty GHM-injected group (n = 8).', 'Eight weeks later, improvement of blood perfusion to the ischemic limb was significantly augmented in the EPO-GHM group compared with any of the control groups. There was no increase in the hemoglobin level, nor was there any increase in endothelial progenitor cells. However, capillary and arteriolar densities were significantly increased in this group. Although the treatment did not affect the levels of vascular endothelial growth factor or interleukin-1 beta, it up-regulated the EPO receptor and matrix metalloproteinase-2 and activated the downstream signaling of Akt and also endothelial nitric oxide synthase in ischemic limbs, which might have been associated with the evident angiogenic and arteriogenic effects in the present system.",
            "output": [
                "Does sustained release of erythropoietin using biodegradable gelatin hydrogel microspheres persistently improve lower leg ischemia?"
            ]
        },
        {
            "id": "task847-bb5f8dde29a541adb17dc3519621f2df",
            "input": "Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence.', 'We compared the number of in situ apoptotic cells by TUNEL assay, expression of active caspase-3 and members of Bcl-2 family by immunohistochemistry; and cell proliferation by the expression of the proliferation markers: PCNA and Ki-67.', 'The proliferation index was low in granulosa of tertiary and cystic follicles of light exposed rats when compared with tertiary follicles of control animals, while in theca interna only cystic follicles presented low proliferation index when compared with tertiary follicles (p < 0.05). The granulosa of cysts exhibited a similar cell DNA fragmentation to early atretic follicles. In the granulosa and theca interna, active caspase-3 shown similar immunostaining levels in tertiary and cystic follicles (p < 0.05). The granulosa cells presented high expression of Bcl-2, Bcl-xL and Bcl-w in the tertiary and cystic follicles with diminishing intensity in the atretic follicles, except with Bcl-w where the intensity was maintained in the atretic follicles (p < 0.05). The expression of Bax was weak in the healthy and cystic follicles. In the theca interna, Bcl-2 expression was the same as the pattern found in the granulosa; no differences were found between tertiary and cystic follicles from both groups for Bcl-xL and Bcl-w. The expression of Bax in this layer was higher in the tertiary follicles of the treated animals (p < 0.05) while the values for cystic follicles were similar to those in the tertiary follicles of controls. The theca externa showed low expression of the pro and anti-apoptotic proteins.",
            "output": [
                "Does an imbalance between apoptosis and proliferation contribute to follicular persistence in polycystic ovaries in rats?"
            ]
        },
        {
            "id": "task847-d2d8055857cb4c1b85a37d7699c7ffaa",
            "input": "The activation of matrix metalloproteinases (MMPs) is a critical event for disruption of the blood-brain barrier (BBB) during cerebral ischemia. Among the MMPs, MMP-2, and MMP-9 expression were reported to be significantly elevated after the onset of ischemia. The aim of this study was to investigate which one is more significant for BBB disruption in the photothrombotic cerebral ischemia.', 'Male Sprague-Dawley rats weighing 250-300 g received focal cerebral ischemia by photothrombosis. MMP-2 and MMP-9 activities were assessed by gelatin zymography at various times from 2 h to 7 days. The BBB integrity was assessed using Evans blue dye with a spectrophotometric assay.', 'The Evans blue extravasation was increased within 2 h after cerebral ischemia, and was maximal at 12 and 24 h after the injury, and then gradually decreased. MMP-9 protein activity was detected as early as 2 h after the focal ischemic event; it rapidly increased at 6 h after ischemia, and reached a maximum level 48 h after the ischemic event. Thereafter, the MMP-9 level abruptly decreased and returned to the baseline at 72 h after the insult. By contrast, the MMP-2 protein activity was up-regulated at 6 h after the focal ischemic insult, and reached a maximum level at 72 h after the event. The elevated MMP-2 levels persisted for 7 days after the injury.",
            "output": [
                "Is early activation of matrix metalloproteinase-9 associated with blood-brain barrier disruption after photothrombotic cerebral ischemia in rats?"
            ]
        },
        {
            "id": "task847-efa4cb309f7846f6a400462f4a18a779",
            "input": "Oxygen free radicals and apoptosis play important roles in liver ischemia/reperfusion (I/R) injury. We sought to investigate the protective effect of calcitonin gene-related peptide (CGRP) to attenuate liver I/R injury due to oxygen free radicals and apoptosis.', 'Harvested rat livers were perfused via the portal vein with 60 mL of 4 degrees C histidine-tryptophan-ketoglutarate (HTK) solution alone in the control group, or with the same solution containing CGRP (3 microg/10 g body weight) in the experimental group. After 24 hours of cold storage, hepatic enzyme leakage, portal venous pressure, oxygen consumption, total adenine nucleotides (TAN), bile production, lipoperoxide (LPO) release, apoptosis, and histochemical changes were evaluated upon 45 minutes of isolated reperfusion.', \"Compared with control livers, CGRP-treated organs showed significantly decreased alanine aminotransferase (ALT) and glutamate-lactate dehydrogenase (GLDH) leakage and portal venous pressure (2.0 +/- 0.3 vs 4.0 +/- 0.4 mmHg; P < .01), with significantly increased bile production (8.56 +/- 0.76 vs 3.34 +/- 0.68 microL/g/45 min; P < .01), oxygen consumption (5.14 +/- 0.4 vs 2.57 +/- 0.2 microL/g/min; P < .01), and total adenine nucleotides (TAN) (11.1 +/- 0.71 vs 7.02 +/- 0.53 micromol/g; P < .01) upon reperfusion as signs of recovered viability. We observed infrequent positive terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) staining, especially in sinusoidal lining cells (SLC). The percentage of TUNEL-positive cells in the CGRP group was significantly decreased compared with the control group: (4.1 +/- 0.67 vs 8.0 +/- 1.27; P < .05). Perfusate levels of low molecular weight (LMW) histone-associated DNA fragments (0.36 +/- 0.04 vs 0.53 +/- 0.06 AU; P < .05) were also decreased, coupled with strong 5'-nucleotidase (5'-NT) and LDH activity staining concentrated on the endothelial cells. LPO release in the perfusate was largely decreased: (0.12 +/- 0.02 vs 0.36 +/- 0.04 nmoL/g, P < .01).",
            "output": [
                "Does pretreatment with calcitonin gene-related peptide attenuate hepatic ischemia/reperfusion injury in rats?"
            ]
        },
        {
            "id": "task847-b4cbab6b400c4af0b7029d31663393e4",
            "input": "Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions.', 'To investigate the therapeutic effects of aprotinin on tissue protection against I/R injury in a rat model. N-acetylcysteine (NAC), a potent antioxidant, was also tested to assess the experimental model.', 'Twenty-four rats were categorized into 3 groups of 8 rats each: those receiving isotonic sodium chloride solution (control group); NAC, 150 mg/kg; and aprotinin, 40,000 KIU/kg. The animals underwent unilateral nephrectomy after 60 minutes of warm ischemia and 60 minutes of reperfusion of the kidney. Malondialdehyde, a lipid peroxidation marker, and antioxidant glutathione levels were measured in the kidney parenchyma. Tissue samples were obtained for histologic analysis.', 'Compared with the control group, the NAC group demonstrated significantly low levels of malondialdehyde (P = .04) and high levels of glutathione (P = .01). At histopathologic analysis, less acute tubular necrosis (ATN) and cellular swelling was noted in the NAC group (P = .002 and P = .005, respectively). In the aprotinin group, histopathologic analysis revealed less tissue damage in terms of ATN (P < .001, cellular swelling (P < .001), and vacuolysis (P = .002). Compared with the NAC group, ATN (P = .01), vacuolysis (P = .04), and congestion (P = .05) were significantly less in the aprotinin group.",
            "output": [
                "Does serine protease inhibitor aprotinin ameliorate renal injury in a rat model of ischemia-perfusion injury?"
            ]
        },
        {
            "id": "task847-e325a773dc914db4a4a0bc6b732320a7",
            "input": "Mild cognitive impairment (MCI) is recognized as a predementia state, but its definition is inconsistent and only 20%-30% develop dementia after 2 years. Biomarkers may help identify individuals at greatest risk of progressive decline. The authors examine a novel neuroimaging technique, diffusion tensor imaging (DTI) as a potential biomarker of MCI.', 'Cross-sectional prospective study.', 'Subjects were recruited randomly using the electoral roll from two electorates in East Sydney, Australia.', 'A community-dwelling sample (N = 249) and age 70-90 years.', 'Screening to exclude dementia, comprehensive neuropsychiatric assessment, cognitive test battery, structural magnetic resonance imaging and DTI to obtain measures of fractional anisotropy (FA) and mean diffusivity (MD). MCI was diagnosed by standard criteria.', 'After controlling for age, sex, and years of education, the amnestic MCI (aMCI) group demonstrated microstructural pathology in the parahippocampal white matter, frontal white matter, splenium of corpus callosum, and posterior cingulate region. The nonamnestic MCI (naMCI) group demonstrated microstructural pathology in the frontal white matter, internal capsule, occipital white matter, and the posterior cingulate region. A binary logistic regression model showed that DTI of the left posterior cingulate was significant in identifying persons with aMCI to an accuracy of 85.1%. Receiver operating characteristics curve analysis yielded a sensitivity of 80% and specificity of 60.3% in distinguishing aMCI from naMCI and the normal comparison group.",
            "output": [
                "Is diffusion tensor imaging of the posterior cingulate a useful biomarker of mild cognitive impairment?"
            ]
        },
        {
            "id": "task847-45e52d31e68647c48f6d2a672439ad3f",
            "input": "Strontium ranelate reduces fracture risk in postmenopausal women with osteoporosis. Evidence from non-clinical studies and analyses of bone markers in phase III trials indicate that this is due to an increase in osteoblast formation and a decrease of osteoclastic resorption. The aim of this work was to investigate, in human cells, the mechanisms by which strontium ranelate is able to influence the activities of osteoblasts and osteoclasts.', 'Human primary osteoblasts were used to examine effects of strontium ranelate on replication (thymidine incorporation), differentiation (Runx2 and alkaline phosphatase) and cell survival (cell counts and caspase activity). Osteoprotegerin (OPG) was measured by quantitative reverse transcription PCR (qRT-PCR) and elisa and receptor activator of NFkappaB ligand (RANKL) by qRT-PCR and Western blot. As strontium ranelate has been proposed as an agonist of the calcium-sensing receptor (CaSR), the involvement of CaSR in the effects of strontium ranelate on OPG and RANKL expression, and cell replication was examined using siRNA.', 'Strontium ranelate increased mRNA and protein levels of OPG and suppressed those of RANKL. Strontium ranelate also stimulated osteoblast replication and differentiation and increased cell survival under stress. Knocking down CaSR suppressed strontium ranelate-induced stimulation of OPG mRNA, reduction of RANKL mRNA, and increase in replication, indicating the involvement of CaSR in these responses.",
            "output": [
                "Do osteoblasts play key roles in the mechanisms of action of strontium ranelate?"
            ]
        },
        {
            "id": "task847-fe68591f6aed4e4283530cb7add32234",
            "input": "Primary hyperparathyroidism, which occurs most commonly in patients with adenomatous disease of a single parathyroid gland, arises as a result of impaired extracellular Ca(2+) (Ca(2+)(o))-dependent feedback on PTH secretion, a process mediated by the calcium-sensing receptor (CaR).', 'Because the Ca(2+)(o) sensitivity of the CaR is positively modulated by L-amino acids, we decided to investigate whether the impaired feedback of PTH secretion in adenomatous parathyroid cells might arise from decreased sensitivity to L-amino acids.', 'Samples of normal and adenomatous human parathyroid cells were prepared by collagenase treatment and then exposed in vitro to various concentrations of Ca(2+)(o) or the CaR-active amino acid, L-phenylalanine (L-Phe).', 'Excess normal parathyroid tissue was obtained from parathyroid autotransplants at the time of thyroid surgery. Samples of adenomatous tissue were obtained from histologically confirmed parathyroid adenomas.', 'The primary measure was sensitivity of Ca(2+)(o)-dependent PTH secretion to the amino acid L-Phe. The secondary measure was sensitivity of Ca(2+)(o)-dependent intracellular Ca(2+) mobilization to L-Phe.', 'Parathyroid adenomas exhibited reduced sensitivity to the CaR-active amino acid L-Phe, which affected both Ca(2+)(o)-dependent PTH secretion and Ca(2+)(o)-dependent intracellular Ca(2+) mobilization as a measure of CaR-dependent signaling in parathyroid cells.",
            "output": [
                "Do adenomatous human parathyroid cells exhibit impaired sensitivity to L-amino acids?"
            ]
        },
        {
            "id": "task847-72d9ee916829429b98259f07285cd574",
            "input": "The gene(s) encoding for endomorphin precursor(s) is/are still unknown. We have raised the possibility of and did find some evidence for a potential de novo biosynthetic route starting from Tyr-Pro precursor. To pursue further this possibility we measured the generation of immunoreactive endomorphin-2 (E2-IR) in adult rat isolated L4,5 dorsal root ganglia.",
            "output": [
                "Is immunoreactive endomorphin 2 generated extracellularly in rat isolated L4,5 dorsal root ganglia by DPP-IV?"
            ]
        },
        {
            "id": "task847-82f541653266450db12c50bd4d49b842",
            "input": "In prior studies of exercise done before or after breakfast and lunch, postprandial activity generally reduces glycemia more than pre-meal. This study sought to examine the effects of exercise before or after an evening meal.', 'Examined the differing effects of a single bout of pre- or postprandial moderate exercise or no exercise on the glycemic response to an evening (dinner) meal in individuals with type 2 diabetes.', 'Community-dwelling participants tested at a research university in Virginia.', 'Twelve men and women subjects (mean age of 61.4+/-2.7 years) with type 2 diabetes treated with diet and/or oral medications.', 'Three trials conducted on separate days consisting of a rest day when subjects consumed a standardized dinner with a moderate glycemic effect and 2 exercise days when they undertook 20 minutes of self-paced treadmill walking immediately before or 15 to 20 minutes after eating.', 'Blood samples taken every 30 minutes over a 4-hour period and later assayed for plasma glucose; from these data both absolute and relative changes in glucose levels were determined, as well as the total glucose area under the curve (AUC) of the 4-hour testing period. Initial samples were additionally assayed for glycated hemoglobin and lipid levels.', 'Twenty minutes of self-paced walking done shortly after meal consumption resulted in lower plasma glucose levels at the end of exercise compared to values at the same time point when subjects had walked pre-dinner. Total glucose AUC over 4-hours was not significantly different among trials.",
            "output": [
                "Is postprandial walking better for lowering the glycemic effect of dinner than pre-dinner exercise in type 2 diabetic individuals?"
            ]
        },
        {
            "id": "task847-fb731d3f05bc4b09a09f039aab20ce55",
            "input": "Anxiety a core feature of panic disorder, is linked to function of the amygdala. Volume alterations in the brain of patients with panic disorder have previously been reported, but there has been no report of amygdala volume association with anxiety.', 'Volumes of hippocampus and amygdala were manually measured using magnetic resonance imaging obtained from 27 patients with panic disorder and 30 healthy comparison subjects. In addition the amygdala was focused on, applying small volume correction to optimized voxel-based morphometry (VBM). State-Trait Anxiety Inventory and the NEO Personality Inventory Revised were also used to evaluate anxiety.', 'Amygdala volumes in both hemispheres were significantly smaller in patients with panic disorder compared with control subjects (left: t = -2.248, d.f. = 55, P = 0.029; right: t = -2.892, d.f. = 55, P = 0.005). VBM showed that structural alteration in the panic disorder group occurred on the corticomedial nuclear group within the right amygdala (coordinates [x,y,z (mm)]: [26,-6,-16], Z score = 3.92, family-wise error-corrected P = 0.002). The state anxiety was negatively correlated with the left amygdala volume in patients with panic disorder (r = -0.545, P = 0.016).",
            "output": [
                "Is smaller amygdala associated with anxiety in patients with panic disorder?"
            ]
        },
        {
            "id": "task847-c75f3f3e84b3406f8fbd7a2c2317ce6f",
            "input": "High-risk human papillomavirus (HPV) is the main etiologic factor for cervical cancer. The severity of HPV-associated cervical lesions has been correlated to the number of infiltrating macrophages. The objective of this work is to characterize the role of tumor-associated macrophages (TAM) on the immune cellular response against the tumor.', 'We used the HPV16 E6- and E7-expressing TC-1 mouse tumor model to study the effect of TAM on T-cell function in vitro, and depleted TAM, using clodronate-containing liposomes, to characterize its role in vivo.', 'TAM, characterized by the positive expression of CD45, F4/80, and CD11b, formed the major population of infiltrating tumor cells. TAM displayed high basal Arginase I activity, producing interleukin-10 (IL-10); they were resistant to iNOSII activity induction, therefore reversion to M1 phenotype, when stimulated in vitro with lipopolysaccharide/IFNgamma, indicating an M2 phentoype. In cultures of isolated TAM, TAM induced regulatory phenotype, characterized by IL-10 and Foxp3 expression, and inhibited proliferation of CD8 lymphocytes. In vivo, depletion of TAM inhibited tumor growth and stimulated the infiltration of tumors by HPV16 E7(49-57)-specific CD8 lymphocytes, whereas depletion of Gr1(+) tumor-associated cells had no effect.",
            "output": [
                "Do hPV16 tumor associated macrophages suppress antitumor T cell responses?"
            ]
        },
        {
            "id": "task847-4defb101a931445db90695d6aec8911b",
            "input": "We evaluated the associations between dual energy X-ray absorptiometry (DXA) and histologically determined cancellous and cortical bone volume by controlling for vascular calcifications and demographic variables in hemodialysis (HD) patients. Femoral bone mineral density (f-BMD) was associated with cortical porosity.', 'Assessment of bone mass in chronic kidney disease patients is of clinical importance because of the association between low bone volume, fractures, and vascular calcifications. DXA is used for noninvasive assessment of bone mass whereby vertebral results reflect mainly cancellous bone and femoral results reflect mainly cortical bone. Bone histology allows direct measurements of cancellous and cortical bone volume. The present study evaluates the association between DXA and histologically determined cancellous and cortical bone volumes in HD patients.', 'In 38 HD patients, DXA was performed for assessment of bone mass, anterior iliac crest bone biopsies for bone volume, and multislice computed tomography for vascular calcifications.', 'While lumbar bone mineral density (l-BMD) by DXA was not associated with histologically measured cancellous bone volume, coronary Agatson score showed a borderline statistically significant association (P = 0.055). When controlled for age and dialysis duration, f-BMD by DXA was associated with cortical porosity determined by histology (P = 0.005).",
            "output": [
                "Does femoral bone mineral density reflect histologically determined cortical bone volume in hemodialysis patients?"
            ]
        },
        {
            "id": "task847-397fd1b4977945a5b240b9572f0376ff",
            "input": "It is possible that interruption of nociceptive input from intervertebral discs can be modulated through bilateral L1 and L2 dorsal root ganglia (DRG) blockade. In order to test this hypothesis, we prospectively collected data from patients with low-lumbar pain, accurately diagnosed as discogenic using provocation discography.', 'Twelve patients were recruited with a mean (sd) symptom duration of 13.7 (8.2) years. Bilateral DRG blocks of L1 and L2 were performed using methylprednisolone 80 mg, clonidine 75 microg and 0.5% bupivacaine 4 ml in each patient.', 'Analysis of Brief Pain Inventories showed no significant change in pain scores.",
            "output": [
                "Does bilateral L1 and L2 dorsal root ganglion block for discogenic low-back pain?"
            ]
        },
        {
            "id": "task847-2ca547e45a0e4d5aa3d16ca9e7cfcd14",
            "input": "Although the major limitation to exercise performance in patients with COPD is dynamic hyperinflation, little is known about its relation to daily physical activity.', 'To analyze the contribution of dynamic hyperinflation, exercise tolerance, and airway oxidative stress to physical activity in patients with COPD.', 'In a cross-sectional study, we included 110 patients with moderate to very severe COPD. Daily physical activity was measured using a triaxial accelerometer providing a mean of 1-minute movement epochs as vector magnitude units (VMU). Patients performed the 6-minute walk test, incremental exercise test with measurement of breathing pattern and operating lung volumes, and constant-work rate test at 75% of maximal work rate.', 'Using the GOLD stage and BODE index, we determined arterial blood gases, lung volumes, diffusing capacity, and biomarkers in exhaled breath condensate. Daily physical activity was lower in the 89 patients who developed dynamic hyperinflation than in the 21 who did not (n =161 [SD 70] vs. n = 288 [SD 85] VMU; P = 0.001). Physical activity was mainly related to distance walked in 6 minutes (r = 0.72; P = 0.001), Vo(2) (r = 0.63; P = 0.001), change in end-expiratory lung volume during exercise (r = -0.73; P = 0.001), endurance time (r = 0.61; P = 0.001), and 8-isoprostane in exhaled breath condensate (r = -0.67; P = 0.001). In a multivariate linear regression analysis using VMU as a dependent variable, dynamic hyperinflation, change in end-expiratory lung volume, and distance walked in 6 minutes were retained in the prediction model (r(2) = 0.84; P = 0.001).",
            "output": [
                "Is daily physical activity in patients with chronic obstructive pulmonary disease mainly associated with dynamic hyperinflation?"
            ]
        },
        {
            "id": "task847-21d3c098f4ae4bfabf68cd6e2dbbdaf7",
            "input": "Provocative clinical tests are often performed in the diagnosis of ulnar neuropathy at the elbow (UNE) although the evidence for the usefulness of these tests is limited. The aim of this study was to determine the diagnostic value of provocative clinical tests in the diagnosis of UNE in a relevant spectrum of patients and controls.', \"A prospective cohort study was performed in consecutive patients clinically suspected of having UNE. All patients underwent a neurological examination and four commonly used provocative clinical tests (Tinel's test, flexion compression test, palpating for local ulnar nerve tenderness and nerve thickening). Subsequently, in all patients a reference standard test comprising electrophysiological studies and neurosonography was independently assessed.\", \"192 eligible patients completed the study protocol. UNE was diagnosed in 137 and an alternative diagnosis was made in 55 patients. The sensitivity, specificity, and positive and negative predictive values were as follows: Tinel's test 62%, 53%, 77% and 30%; flexion compression test 61%, 40%, 72% and 29%; palpating for nerve thickening 28%, 87%, 84% and 33%; and palpating for nerve tenderness 32%, 80%, 80% and 32%. Logistic regression and receiver operating characteristic curves showed that the added value of one or more provocative tests over routine clinical examination is minimal.",
            "output": [
                "Is the diagnostic value of provocative clinical tests in ulnar neuropathy at the elbow marginal?"
            ]
        },
        {
            "id": "task847-b31ee54049d4416894c8eae94bc5eab0",
            "input": "The aim of the present study was to evaluate whether thyroid hormonal changes during menopause may affect the development and the course of major depressive disorder.', 'Thirty-nine female patients (n = 17 in pre-menopause; n = 22 in post-menopause) with major depressive disorder based on Diagnostic Statistical Manual of Mental Disorders (4th edition) criteria and who were euthyroid and not on hormonal replacement therapy, participated in a prospective, 6-week, open-label naturalistic study. The Hamilton Depression Rating Scale-17 item, the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression scale and the Cognitive Failure Questionnaire were administered at baseline, week 1, week 3, and week 6. Levels of thyroid stimulating hormone, total thyroxine and total triiodothyronine were collected at baseline visit.', 'In the whole sample, particularly in pre-menopausal women, levels of thyroid stimulating hormone-potential markers of subclinical hypothyroidism were correlated with those of less severe but more resistant depressive form. Conversely, total thyroxine levels were correlated with a more severe depression, but high levels of this hormone favored the response to antidepressants. Overall, a diagnosis of subclinical hypothyroidism was associated with a poor response to antidepressant treatment. Finally, total triiodothyronine levels were associated with better cognitive functioning, though they did not influence improvement occurring with recovery.",
            "output": [
                "Do thyroid hormones affect recovery from depression during antidepressant treatment?"
            ]
        },
        {
            "id": "task847-d4845ca94e414383a8c7ee5f56c4e4ba",
            "input": "Trials with healthy volunteers have shown that emergency ambulance transportation induces stress, which becomes evident by an increase in heart rate, blood pressure and plasma levels of stress hormones such as adrenaline, noradrenaline, cortisol and prolactin. A study was undertaken to test the hypothesis that emergency ambulance transportation may also lead to stress in patients with acute coronary syndrome.', 'Venous plasma levels of epinephrine, norepinephrine and lactate as well as visual analogue scale (VAS) scores for pain and anxiety were measured in 32 patients with defined clinical signs of acute coronary syndrome before and after transportation. Heart rate, blood pressure and transcutaneous oxygen saturation levels were recorded every 3 min.', 'Mean (SD) plasma levels of epinephrine and norepinephrine increased significantly (p<0.01) during transportation (159.29 (55.34) ng/l and 632.53 (156.32) ng/l before transportation vs 211.03 (70.12) ng/l and 782.93 (173.95) ng/l after transportation), while lactate levels, heart rate and mean blood pressure remained almost stable. There was no significant change in mean (SD) VAS scores for pain and anxiety (3.79 (3.70) and 2.89 (3.01) vs 2.13 (3.30) and 1.57 (2.78)).",
            "output": [
                "Does emergency ambulance transport induce stress in patients with acute coronary syndrome?"
            ]
        },
        {
            "id": "task847-edd420be25d04a3abb7844cd9a324711",
            "input": "An iron deficiency is often present in haemodialysis (HD) patients; however, although transferrin saturation (TSAT) of <20% and/or serum ferritin of <200 ng/mL should express iron scarcity, in HD patients high ferritin levels could be related to inflammation rather than reflecting optimal iron stores.', 'The aim of the present study was to evaluate serum levels of neutrophil gelatinase-associated lipocalin (NGAL), a small siderophore-binding protein, in a cohort of 56 chronic HD patients in order to determine its possible relationships with iron status.', 'NGAL levels were markedly higher in HD patients than in healthy controls; furthermore, HD patients with TSAT <20% had lower NGAL values than healthy controls, whereas the correction of iron deficiency by means of chronic i.v. iron administration significantly increased NGAL values from baseline. Findings from univariate and multivariate analyses demonstrated that NGAL was a significant predictor of hsCRP, spKT/V and TSAT. In ROC analysis, a NGAL cut-off level of <or=473 ng/mL had a greater sensitivity and specificity than a ferritin level of <200 ng/mL in identifying iron deficiency among HD patients.",
            "output": [
                "Does neutrophil gelatinase-associated lipocalin ( NGAL ) reflect iron status in haemodialysis patients?"
            ]
        },
        {
            "id": "task847-97e98aa90bec4e9080eec9b96462b60c",
            "input": "Hypoxia plays an important role in kidney injury. By the stabilization of the transcription factor HIF-1, hypoxia affects gene expression also in tubular epithelial cells. Increased expression of connective tissue growth factor (CTGF) is observed in different kidney diseases and is associated with deteriorating renal function. Therefore, we hypothesized that the expression of CTGF might be modulated under hypoxic conditions.', 'The human proximal tubular epithelial cell lines HK-2 and HKC-8 were treated with reduced oxygen tension (1% O(2)) or the hypoxia mimetic dimethyloxalyl glycine (DMOG). CTGF was analysed by Western blotting, real-time RT-PCR and luciferase gene expression assays.', 'Exposure of HK-2 or HKC-8 cells to hypoxia or treatment with DMOG for up to 24 h reduced cellular as well as secreted CTGF protein synthesis. Downregulation was also detectable at the mRNA level and was confirmed by reporter gene assays. Hypoxic repression of CTGF synthesis was dependent on HIF-1, as shown by HIF-1alpha knockdown by siRNA. Furthermore, exposure to hypoxia reduced CTGF synthesis in response to TGF-beta. A negative correlation between HIF-1alpha accumulation and CTGF synthesis was also observed in renal cell carcinoma cells (RCC4 and RCC10). Reexpression of von Hippel-Lindau protein reduced HIF-1alpha and increased CTGF synthesis.",
            "output": [
                "Does hypoxia interfere with connective tissue growth factor ( CTGF ) gene expression in human proximal tubular cell lines?"
            ]
        },
        {
            "id": "task847-cefcd645ff9b431ca3afbce8706301d1",
            "input": "Hyaluronic acid binding protein 1 (HABP1), a family of proteins interacting with hyaluronan (HA), had been associated with cell adhesion and tumor invasion. The aim of this study was to investigate the correlation between clinicopathologic factors and patient survival time with the expression of HABP1 in breast cancer patients.', 'Expression of HABP1 mRNA and protein were detected with real-time quantitative PCR and immunohistochemical staining in 63 breast cancer and non-cancerous matched tissues.', \"The mRNA expression level of HABP1 was unrelated to the patient's age, tumor size, histological grade, TNM stage. However, it proved to be positively related to axillary nodes metastasis (P = 0.008). Furthermore, it was shown that the survival rate of patients with low HABP1 expression was significantly higher than that of patients with high HABP1 expression (P = 0.025). Multivariate analysis revealed that HABP1 mRNA expression level was a significant factor for predicting prognosis (P = 0.022). The immunohistochemistry results showed that the expression level of HABP1 in breast cancer cells was higher than that in normal breast cells.",
            "output": [
                "Is increased expression of hyaluronic acid binding protein 1 correlated with poor prognosis in patients with breast cancer?"
            ]
        },
        {
            "id": "task847-8bfade9402d24124bed6481d48d7e104",
            "input": "Morphine consumption can vary widely between individuals even for identical surgical procedures. As mu-opioid receptor (OPRM1) is known to modulate pain perception and mediate the analgesic effects of opioid compounds in the central nervous system, we examined the influence of two OPRM polymorphisms on acute post-operative pain and morphine usage in women undergoing elective caesarean delivery.', 'Data on self-reported pain scores and amount of total morphine use according to patient-controlled analgesia were collected from 994 women from the three main ethnic groups in Singapore. We found statistically significant association of the OPRM 118A>G with self-administered morphine during the first 24-hour postoperative period both in terms of total morphine (p = 1.7 x 10(-5)) and weight-adjusted morphine (p = 6.6 x 10(-5)). There was also significant association of this OPRM variant and time-averaged self-rated pain scores (p = 0.024). OPRM 118G homozygotes used more morphine and reported higher pain scores than 118A carriers. Other factors which influenced pain score and morphine usage include ethnicity, age and paying class.",
            "output": [
                "Do ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain?"
            ]
        },
        {
            "id": "task847-4ddde4cf67184d1f9e779cc7104d508f",
            "input": "Ets transcription factors have been widely implicated in the control of tumorigenesis, with most studies suggesting tumor-promoting roles. However, few studies have examined Ets tumorigenesis-modifying functions in vivo using model genetic systems.', 'Using mice expressing a previously characterized Ets dominant repressor transgene in the intestinal epithelium (Villin-En/Erm), we examined the consequences of blocking endogenous Ets-mediated transcriptional activation on tumorigenesis in the ApcMin model of intestinal carcinoma.', 'En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in ApcMin animals. Moreover, when examined histologically, tumors from En/Erm-expressing animals show a trend toward greater stromal invasiveness. Detailed analysis of crypt-villus homeostasis in these En/Erm transgenic animals suggests increased epithelial turnover as one possible mechanism for the enhanced tumorigenesis.",
            "output": [
                "Does the Ets dominant repressor En/Erm enhance intestinal epithelial tumorigenesis in ApcMin mice?"
            ]
        },
        {
            "id": "task847-21cc840c0ca84599b85497475b4bef9a",
            "input": "Topical haemostatic agents are used to help achieve haemostasis during surgery when standard surgical techniques are insufficient. The objective of this study was to confirm the safety profile of an equine collagen patch coated with human fibrinogen and human thrombin with particular focus on the occurrence of thromboembolic events (TEEs), major bleeding and immunological events.', 'This was a non-interventional, multicentre, prospective, surveillance study in which a collagen fleece-bound fibrin sealant was prescribed in accordance with its marketing authorisation. The decision to use the sealant was based solely on current surgical practice. All patients that received the sealant and provided informed consent were included. TEEs (any coagula-based occlusion in a vessel or the heart identified by symptomatic clinical signs and/or verified by paraclinical examination), major bleeding (any bleeding that required intervention), and immunological events (hypersensitivity including anaphylaxis) that occurred during surgery, post-operative hospital stay or 6 months of follow-up were reported as adverse events. The primary endpoint was the proportion of patients experiencing a confirmed TEE.', 'A total of 3098 patients were recruited at 227 centres in 12 European countries. The most frequent types of surgery were hepatic (33%), gastrointestinal (16%) and urological (14%) and the main indication for surgery was for primary (35%) or secondary (20%) malignancy. Forty-six patients (1.5%, 95% CI 1.1-2.0%) had at least one TEE during the study. The most commonly reported TEEs were pulmonary embolism or post-procedural pulmonary embolism (n = 18) and deep vein thrombosis (n = 9). There were 64 major bleedings in 62 patients and 9 immunological events in 8 patients.",
            "output": [
                "Is collagen fleece-bound fibrin sealant associated with an increased risk of thromboembolic events or major bleeding after its use for haemostasis in surgery : a prospective multicentre surveillance study?"
            ]
        },
        {
            "id": "task847-0bbd2640e03243838d00431d73e0156c",
            "input": "T(H)1 cell-mediated immunity is essential for host defense against a variety of intracellular pathogens, such as mycobacteria, salmonella, and Leishmania species. A major T(H)1-mediated effector mechanism involves the IFN-gamma-induced killing of the pathogen by infected macrophages.', 'The range of known T(H)1-specific effector molecules is limited, especially in human subjects. We sought to identify novel effector molecules that might be involved in T(H)1-mediated pathogen clearance.', 'We performed microarray-based analysis of human T(H)1 and T(H)2 cells to identify T(H)1-specific molecules. These analyses identified the extracellular matrix molecule fibronectin as a highly expressed T(H)1-specific molecule. We examined the expression of fibronectin in a variety of human cell types by using real-time RT-PCR, ELISA, and Western blotting. We also studied the role of fibronectin in modulating monocyte phenotype using in vitro culture.', 'We show that human T(H)1 cells constitutively express and secrete fibronectin after in vitro differentiation from naive precursors. Furthermore, we demonstrate that ex vivo human T(H)1 cells selectively express fibronectin when compared with T(H)2 cells. The predominant isoform of fibronectin expressed by T(H)1 cells contains additional domains of the protein responsible for alpha4beta1 integrin binding and activation of Toll-like receptor 4. We show that treatment of monocytes with T(H)1 cell-derived fibronectin induces expression of the proinflammatory cytokine IL-6 while inhibiting IL-10 expression.",
            "output": [
                "Is fibronectin a TH1-specific molecule in human subjects?"
            ]
        },
        {
            "id": "task847-340905bb643b41e09c8afba7da85b3a5",
            "input": "Nitric oxide (NO) has previously been shown to inhibit human rhinovirus (HRV) replication in airway epithelial cells and to inhibit rhinovirus-induced epithelial cytokine and chemokine production independently of its effects on viral replication by modulating nuclear translocation and binding of transcription factors.', 'To define the molecular mechanisms by which NO inhibits HRV-16-induced epithelial production of CXCL10 by affecting nuclear translocation and binding of nuclear factor-kappaB (NF-kappaB) and IFN regulatory factor 1 (IRF-1).', 'Cultured human airway epithelial cells were infected with HRV-16 in the absence or presence of a NO donor, or were preincubated with 2 highly selective inhibitors of inhibitor of kappaB kinase (IKK)beta and then infected with HRV-16. Effects on the NF-kappaB and IRF-1 pathways were examined by using electrophoretic mobility shift assays, Western blotting, and real-time RT-PCR.', 'Nitric oxide directly inhibited the binding of both recombinant NF-kappaB p50 protein and recombinant IRF-1 to their recognition sequences from the CXCL10 promoter. NO also inhibited phosphorylation of the NF-kappaB inhibitor, IkappaBalpha, in HRV-16-infected cells. In addition, both NO and inhibitors of IKKbeta inhibited viral induction of IRF-1 mRNA and protein.",
            "output": [
                "Does nitric oxide inhibit IFN regulatory factor 1 and nuclear factor-kappaB pathways in rhinovirus-infected epithelial cells?"
            ]
        },
        {
            "id": "task847-4556a59d920541db8f7e329390f3eeb8",
            "input": "Secreted phospholipases A(2) (sPLA(2)s) are released in plasma and other biologic fluids of patients with inflammatory, autoimmune, and allergic diseases.', 'We sought to evaluate sPLA(2) activity in the bronchoalveolar lavage fluid (BALF) of asthmatic patients and to examine the expression and release of sPLA(2)s from primary human lung mast cells (HLMCs).', 'sPLA(2) activity was measured in BALF and supernatants of either unstimulated or anti-IgE-activated HLMCs as hydrolysis of oleic acid from radiolabeled Escherichia coli membranes. Expression of sPLA(2)s was examined by using RT-PCR. The release of cysteinyl leukotriene (LT) C(4) was measured by means of enzyme immunoassay.', 'Phospholipase A(2) (PLA(2)) activity was higher in the BALF of asthmatic patients than in the control group. BALF PLA(2) activity was blocked by the sPLA(2) inhibitors dithiothreitol and Me-Indoxam but not by the cytosolic PLA(2) inhibitor AZ-1. HLMCs spontaneously released a PLA(2) activity that was increased on stimulation with anti-IgE. This PLA(2) activity was blocked by dithiothreitol and Me-Indoxam but not by AZ-1. HLMCs constitutively express mRNA for group IB, IIA, IID, IIE, IIF, III, V, X, XIIA, and XIIB sPLA(2)s. Anti-IgE did not modify the expression of sPLA(2)s. The cell-impermeable inhibitor Me-Indoxam significantly reduced (up to 40%) the production of LTC(4) from anti-IgE-stimulated HLMCs.",
            "output": [
                "Are lung mast cells a source of secreted phospholipases A2?"
            ]
        },
        {
            "id": "task847-df2b4686905c4b3cba7f71b792019636",
            "input": "Although some mechanisms of habitat adaptation of conspecific populations have been recently elucidated, the evolution of female preference has rarely been addressed as a force driving habitat adaptation in natural settings. Habitat adaptation of fire salamanders (Salamandra salamandra), as found in Middle Europe (Germany), can be framed in an explicit phylogeographic framework that allows for the evolution of habitat adaptation between distinct populations to be traced. Typically, females of S. salamandra only deposit their larvae in small permanent streams. However, some populations of the western post-glacial recolonization lineage use small temporary ponds as larval habitats. Pond larvae display several habitat-specific adaptations that are absent in stream-adapted larvae. We conducted mate preference tests with females from three distinct German populations in order to determine the influence of habitat adaptation versus neutral genetic distance on female mate choice. Two populations that we tested belong to the western post-glacial recolonization group, but are adapted to either stream or pond habitats. The third population is adapted to streams but represents the eastern recolonization lineage.', 'Despite large genetic distances with FST values around 0.5, the stream-adapted females preferred males from the same habitat type regardless of genetic distance. Conversely, pond-adapted females did not prefer males from their own population when compared to stream-adapted individuals of either lineage.",
            "output": [
                "Does habitat adaptation rather than genetic distance correlate with female preference in fire salamanders ( Salamandra salamandra )?"
            ]
        },
        {
            "id": "task847-3c8ec82cb2a64964b9f3879fe0d2b9e4",
            "input": "To explore the associations between the presence of personality problems and somatic morbidity and health care utilisation.', 'The Iowa Personality Disorder Screen was administered in order to identify persons with personality problems in a Norwegian population survey (the Oslo Health Study - HUBRO). Cases consisted of 369 individuals, 30, 40 and 45 years of age with personality problems matched on age and gender with five controls each. Data on somatic morbidity and health care utilisation were collected by questionnaires.', 'The cases more frequently reported persistent muscular pain, asthma, fibromyalgia and alcohol problems than the controls. They also more often used nonprescribed analgesics and antidepressants. The cases more frequently had consulted a general practitioner (GP) in the last 12 months, less frequently got referral to somatic specialist care and were less satisfied with their last visit to a GP.",
            "output": [
                "Are personality problems considerably associated with somatic morbidity and health care utilisation?"
            ]
        },
        {
            "id": "task847-eb7f04a4b79743d2911c95be16fd48b1",
            "input": "Response shift is generally associated with a change in the meaning of test scores, impeding the comparison of repeated measurements. Still, different researchers have different views of response shift. From a measurement perspective, response shift can be considered as bias in the measurement of change, whereas from a more conceptual perspective, it can be considered as bias in the explanation of change. We propose definitions to accommodate both interpretations of response shift.', 'Formal definitions of measurement bias and explanation bias serve to define response shift in measurement and conceptual perspectives. Examples from the field of health-related quality of life research illustrate the definitions.', 'Definitions of response shifts as special cases of either measurement bias or explanation bias clarify different interpretations of response shift and lead to different research methods. Different structural equation models are suggested to investigate biases and response shifts in each of the two perspectives.",
            "output": [
                "Do formal definitions of measurement bias and explanation bias clarify measurement and conceptual perspectives on response shift?"
            ]
        },
        {
            "id": "task847-33283088e7dd42a3bef82280c3426f8c",
            "input": "The effect of inhalational anesthetics on sensory-evoked unit activity in the cerebral cortex has been controversial. Desflurane has desirable properties for in vivo neurophysiologic studies, but its effect on cortical neuronal activity and neuronal responsiveness is not known. The authors studied the effect of desflurane on resting and visual evoked unit activity in rat visual cortex in vivo.', 'Desflurane was administered to adult albino rats at steady-state concentrations at 2%, 4%, 6%, and 8%. Flashes from a light emitting diode were delivered to the left eye at 5-s intervals. Extracellular unit activity within the right visual cortex was recorded using a 49-electrode array. Individual units were identified using principal components analysis.', 'At 2% desflurane, 578 active units were found. Of these, 75% increased their firing rate in response to flash. Most responses contained early (0-100 ms) and late (150-1000 ms) components. With increasing desflurane concentration, the number of units active at baseline decreased (-13%), the number of early-responding units increased (+31%), and number of late-responding units decreased (-15%). Simultaneously, baseline firing rate decreased (-77%), the early response was unchanged, and the late response decreased (-60%).",
            "output": [
                "Does desflurane selectively suppress long-latency cortical neuronal response to flash in the rat?"
            ]
        },
        {
            "id": "task847-69cf475761514b62bf4c1f53429a0d9b",
            "input": "The objective of this study was to determine if later toilet training is associated with urge incontinence in children.', 'We used a case-control study design to yield level 2 evidence.', 'Initiation of toilet training after 32 months of age was associated with urge incontinence (P=0.02).",
            "output": [
                "Is later toilet training associated with urge incontinence in children?"
            ]
        },
        {
            "id": "task847-6338deff99be4dc5b8edbf3696ca0c05",
            "input": "The DAZ family genes boule, daz and dazl encode RNA binding proteins essential for fertility of diverse animals including human. dazl has bisexual expression in both mitotic and meiotic germ cells, whereas daz has male premeiotic expression, and boule is largely a unisexual meiotic regulator. Although boule has been proposed as the ancestor for dazl/daz by gene duplication, it has been identified only in invertebrates and mammals. It has, however, remained unclear when and how the DAZ family has evolved in vertebrates.', \"This study was aimed at identifying and characterizing the DAZ family genes in fish as the basal vertebrate. We show that boule and dazl coexist in medaka and stickleback. Similar to the medaka dazl (Odazl), the medaka boule (Obol) is maternally supplied and segregates with primordial germ cells. Surprisingly, Obol is expressed in adult germ cells at pre-meiotic and meiotic stages of spermatogenesis and oogenesis. However, the maximal meiotic Obol expression in spermatocytes contrasts with the predominant pre-meiotic Odazl expression in spermatogonia, and the diffuse cytoplasmic Obol distribution in early oocytes contrasts with the Odazl concentration in the Balbinani's body.",
            "output": [
                "Is boule present in fish and bisexually expressed in adult and embryonic germ cells of medaka?"
            ]
        },
        {
            "id": "task847-4ce0b61d66d849ab863b324854797227",
            "input": "To investigate whether preconditioning with high mobility group box 1 protein (HMGB1) could reduce myocardial ischemia-reperfusion (I/R) injury.', 'Infarct size, lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-6 (IL-6) were assessed. HMGB1 preconditioning reduced significantly the infarct size induced by I/R. The LDH, CK, TNF-\u03b1 and IL-6 levels were significantly decreased by HMGB1 preconditioning compared to those in the I/R group.",
            "output": [
                "Does preconditioning with high mobility group box 1 protein protect against myocardial ischemia-reperfusion injury?"
            ]
        },
        {
            "id": "task847-8eedcbdb45d7462685294ec143aeab66",
            "input": "Plasminogen Activator Inhibitor-1 (PAI-1) is the most potent endogenous inhibitor of fibrinolysis which is implicated in the pathogenesis of myocardial infarction and metabolic syndrome. The formation of reactive oxygen species (ROS) plays an important role in the pathology of vascular disorders and has been shown to increase PAI-1 expression by endothelial cells. Growing evidence indicates that NADPH oxidase and in particular the constitutively active Nox4-p22(phox) complexes are major sources of ROS in endothelial cells. The aim of the present study was to characterize the role of NADPH oxidase and in particular Nox4 in the regulation of PAI-1 expression in cultured Human Umbilical Venous Endothelial Cells (HUVECs).', 'N-acetylcysteine (NAC, scavenger of ROS), diphenylene iodonium chloride (DPI, inhibitor of flavoproteins), M40403 (superoxyde dismutase mimic) and S17834 (inhibitor of NADPH oxidase) inhibited PAI-1 release and promoter activity in HUVECs. Specific knock down of Nox4 mRNA by siRNA caused a decrease in ROS production and NADPH oxidase activity. Moreover, Nox4 silencing decreased PAI-1 expression, release and activity as well as p38 MAPK pathways and NFkappaB activation. These signalling pathways are also involved in PAI-1 release.",
            "output": [
                "Does nox4 mediate the expression of plasminogen activator inhibitor-1 via p38 MAPK pathway in cultured human endothelial cells?"
            ]
        },
        {
            "id": "task847-2d7f75bb04304fd4812cb0a200665f56",
            "input": "Previous follow-up studies indicate that increased visual cortical, ventral cingulate and subcortical responses of depressed individuals to sad facial stimuli, but not happy stimuli could represent reversible markers of disease severity. We hypothesized that greater responses in these areas to sad stimuli, but not happy stimuli, would predict better subsequent clinical outcome. We also explored areas that would predict a poor outcome.', 'Twelve melancholically depressed individuals in the early stages of antidepressant treatment in a secondary care setting participated in two experiments comparing responses to varying intensities of sad and happy facial stimuli, respectively, using event related functional MRI. They repeated the experiments after a mean delay of 12 weeks of treatment.', 'There was a variation in response to treatment. Greater right visual cortex and right subgenual cingulate (R-BA25) responses to sad stimuli, but not happy stimuli, in the early stages of treatment were associated with a good clinical outcome. Greater ventrolateral prefrontal cortex responses to either stimulus type were associated with a relatively poor outcome.",
            "output": [
                "Do subgenual cingulate and visual cortex responses to sad faces predict clinical outcome during antidepressant treatment for depression?"
            ]
        },
        {
            "id": "task847-f1c5559347cf4df1b3fd72368a51ddf8",
            "input": "The Notch signaling pathway has been shown to play a role in bone marrow-derived stromal cell differentiation, however, the precise outcome of Notch activation remains controversial. The aim of this study was to evaluate the effect of Notch signaling in primary human bone marrow-derived stromal cells (hBMSCs).', 'hBMSCs were transduced to >90% with lentiviral vectors containing either human notch1 intracellular domain (NICD), jagged1, or dominant negative mastermind1. Cells were exposed to adipogenic and osteogenic differentiation stimuli and differentiation was quantified by oil red or alizarin red staining, alkaline phosphatase liver/bone/kidney (ALPL) activity and expression of adipogenic or osteogenic marker genes.', 'NICD and jagged1 transgene-expressing hBMSCs demonstrated enhanced mineralization, nodule formation, and ALPL activity in osteogenic differentiation media. These findings correlated with increased gene expression of bone morphogenetic protein 2 and ALPL. In contrast, NICD or jagged1 transgene expression strongly inhibited adipocyte formation and reduced peroxisome proliferator-activated receptor-gamma, fatty acid binding protein 4, and adiponectin precursor gene expression. Co-overexpression of dominant negative mastermind1 and NICD or jagged1 led to a partial rescue of the differentiation phenotypes. In addition, high endogenous jagged1 expression levels were observed in hBMSCs samples with strong ALPL activity compared to a group of samples with low ALPL activity.",
            "output": [
                "Does notch signaling enhance osteogenic differentiation while inhibiting adipogenesis in primary human bone marrow stromal cells?"
            ]
        },
        {
            "id": "task847-951fab2845874497b501a6d5ea454f2c",
            "input": "To compare oncologic outcomes in a contemporary series of patients undergoing radical cystectomy (RCX) by the laparoscopic or open approach.', 'Laparoscopic RCX with extracorporeally constructed urinary diversion is a safe and effective operation for appropriate patients with bladder cancer. Perioperative and functional outcomes are comparable with open surgery. Worldwide experience continues to increase; more than 1000 surgeries have already been performed. Intermediate-term oncologic outcomes appear to be comparable to open approach.",
            "output": [
                "Are the oncologic results of laparoscopic radical cystectomy ( yet ) equivalent to open cystectomy?"
            ]
        },
        {
            "id": "task847-fb96bc4bf0dd46d3ac7b850ed2f75496",
            "input": "We investigated the pharmacological effect of TRPV1 antagonists in anesthetized rodent models of bladder function.', 'The TRPV1 antagonists JNJ17203212 and JYL1421 were evaluated in the anesthetized rat volume induced micturition reflex model. JNJ17203212 was further evaluated in this model in capsaicin (Sigma) desensitized rats, and in rat capsaicin and mouse citric acid models of irritant induced detrusor overactivity.', 'Systemic JNJ17203212 and JYL1421 administration in the anesthetized rat volume induced micturition reflex model resulted in an increased micturition threshold volume. JNJ17203212 also decreased bladder contraction amplitude but JYL1421 had no effect. Capsaicin desensitization significantly increased baseline micturition threshold volume and decreased bladder contraction amplitude in the volume induced micturition reflex model compared to those in sham treated controls and JNJ17203212 produced no further effect after capsaicin desensitization. JNJ17203212 was also effective in 2 models of irritant induced detrusor overactivity, preventing the decrease in micturition threshold volume and the increase in bladder contraction amplitude observed with intravesical instillation of 10 microM capsaicin, and the decreased voiding interval induced by intravesical citric acid.",
            "output": [
                "Does selective pharmacological blockade of the TRPV1 receptor suppress sensory reflexes of the rodent bladder?"
            ]
        },
        {
            "id": "task847-03c2aa0f2b2f4796b960372dd2193bf3",
            "input": "There is a need in urological practice to identify new bladder cancer molecular markers to further develop noninvasive diagnostic tests. We analyzed bladder cancer gene expression profiles to determine the relevant differentially expressed genes and whether this differential expression is maintained in urine samples.', 'We collected 55 tissue specimens from a total of 43 patients with bladder cancer and 12 controls, and 49 urine samples from bladder washings from a total of 36 patients with bladder cancer and 13 controls between September 2003 and December 2004. DNA microarrays (GeneChip Human Genome U133 Plus 2.0 Array) were used to identify differentially expressed genes at 3 bladder cancer stages. Selected differentially expressed genes were validated in an independent set of bladder washings by quantitative reverse transcriptase-polymerase chain reaction.', 'Unsupervised cluster analysis of DNA microarray data showed a clear distinction in control vs tumor samples and low vs high grade tumors. Genes with at least 2-fold differential expression in controls vs tumors (2,937 probe sets or 2,295 genes) and in low vs high grade tumors (674 probe sets or 530 genes) were identified and ranked. Gene expression measurements in bladder washings of the 6 most differentially expressed genes in controls vs tumors were confirmed for the 2 over expressed genes tested by quantitative reverse transcriptase-polymerase chain reaction. All 8 selected differentially expressed genes in low vs high grade tumors were confirmed in bladder washing samples.",
            "output": [
                "Does dNA microarray expression profiling of bladder cancer allow identification of noninvasive diagnostic markers?"
            ]
        },
        {
            "id": "task847-3ddf8e3b25354f1c91d54e6bd40bcf8d",
            "input": "The International Diabetes Federation (IDF) global definition of metabolic syndrome suggests using race- and gender-specific waist circumference (WC) cutoffs. Previously, we have hypothesized that need for gender- and race-specific cutoffs could be obviated by supplanting WC with index of central obesity (ICO). The aim of this study was to test the utility of ICO in defining metabolic syndrome.', 'Data were collected from National Health and Nutrition Examination Survey (NHANES) database for year 2005-2006. Subjects were analyzed for presence of metabolic syndrome using National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The IDF definition was modified by replacing WC with ICO. Sensitivity and specificity of the IDF definition and modified definition were compared against the NCEP ATP III definition.', 'Using a modified IDF definition, a common cutoff of 0.53 could be obtained for both males and females. The modified IDF definition improved sensitivity from 0.85 to 0.98 and 0.98 to 0.99 among males and females, respectively. This was at the cost of compromised specificity, which reduced from 1.0 to 0.89 and 0.98 for males and females, respectively.",
            "output": [
                "Is index of central obesity better than waist circumference in defining metabolic syndrome?"
            ]
        },
        {
            "id": "task847-c4a3fbbe5001439ea0f2cfa657c2c070",
            "input": "Gastric cancers frequently show chromosomal alterations which can cause activation of oncogenes, and/or inactivation of tumour suppressor genes. In gastric cancer several chromosomal regions are described to be frequently lost, but for most of the regions, no tumour suppressor genes have been identified yet. The present study aimed to identify tumour suppressor genes inactivated by nonsense mutation and deletion in gastric cancer by means of GINI (gene identification by nonsense mediated decay inhibition) and whole genome copy number analysis.', 'Two non-commercial gastric cancer cell lines, GP202 and IPA220, were transfected with siRNA directed against UPF1, to specifically inhibit the nonsense mediated decay (NMD) pathway, and with siRNA directed against non-specific siRNA duplexes (CVII) as a control. Microarray expression experiments were performed in triplicate on 4 x 44 K Agilent arrays by hybridizing RNA from UPF1-transfected cells against non-specific CVII-transfected cells. In addition, array CGH of the two cell lines was performed on 4 x 44K agilent arrays to obtain the DNA copy number profiles. Mutation analysis of GINI candidates was performed by sequencing.', 'UPF1 expression was reduced for >70% and >80% in the GP202 and IPA220 gastric cancer cell lines, respectively. Integration of array CGH and microarray expression data provided a list of 134 and 50 candidate genes inactivated by nonsense mutation and deletion for GP202 and IPA220, respectively. We selected 12 candidate genes for mutation analysis. Of these, sequence analysis was performed on 11 genes. One gene, PLA2G4A, showed a silent mutation, and in two genes, CTSA and PTPRJ, missense mutations were detected. No nonsense mutations were detected in any of the 11 genes tested.",
            "output": [
                "Does nMD inhibition fail to identify tumour suppressor genes in microsatellite stable gastric cancer cell lines?"
            ]
        },
        {
            "id": "task847-e3def8cab32040a4909c4d655dc7bb82",
            "input": "Although many factors predictive of patient survival have been reported for lung cancer, no comparative studies have attempted to determine those that are most significant for practical medicine.', 'We conducted a retrospective review of 139 patients who underwent complete resection of adenocarcinomas less than 2 cm in diameter between 1993 and 2000 at the National Cancer Center Hospital (Tokyo, Japan). The MIB-1 labeling index (LI), immunohistochemical staining for carcinoembryonic antigen (CEA), p53, p27, epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), Cox-2, neuronatin, gammaH2AX, and thyroid transcription factor-1 (TTF-1), the prevalence of a micropapillary pattern, and the ratio of the bronchioloalveolar cell carcinoma (BAC) or lepidic growth (LG) component were determined, and their significance as prognostic factors for lung adenocarcinoma was compared.', 'Univariate analysis showed that lymph node metastasis (p-N status), BAC/LG component, vascular invasion (p-V status), MIB-1 LI, pEGFR, and CEA were prognostically significant (p-N status: p < 0.0001, BAC/LG: p = 0.0005, p-V status: 0.002, MIB-1 LI: p = 0.005, pEGFR: p = 0.024, and CEA: p = 0.049). Multivariate analysis showed that only p-N status (p = 0.013) was of prognostic significance. However, BAC/LG component (p = 0.051) was a more reliable prognostic factor than p-N status in mixed adenocarcinoma with a BAC/LG component.",
            "output": [
                "Is bronchioloalveolar carcinoma ( lepidic growth ) component a more useful prognostic factor than lymph node metastasis?"
            ]
        },
        {
            "id": "task847-ce69e5bcb5e4453c9f8c5e89f552967d",
            "input": "Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. NSCLC is the most lethal human cancer due to its high rate of metastasis.', 'Lack of a suitable animal model has so far hampered analysis of metastatic progression. We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c-MYC alone induced frank tumor growth only after long latency at which time secondary mutations in K-Ras or LKB1 were detected reminiscent of human NSCLC. Combination with C-RAF led to immediate acceleration of tumor growth, conversion to papillary epithelial cells and angiogenic switch induction. Moreover, addition of c-MYC was sufficient to induce macrometastasis in liver and lymph nodes with short latency associated with lineage switch events. Thus we have generated the first conditional model for metastasis of NSCLC and identified a gene, c-MYC that is able to orchestrate all steps of this process.",
            "output": [
                "Is mYC a metastasis gene for non-small-cell lung cancer?"
            ]
        },
        {
            "id": "task847-3027d15bc0a84269b76008af81357f76",
            "input": "Renal ischemia-reperfusion (I/R) injury is a major cause of acute renal failure (ARF). The transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated as a key mediator of reperfusion injury. Activation of NF-kappaB is dependent upon the phosphorylation of its inhibitor, IkappaB, by the specific inhibitory kappaB kinase (IKK) subunit, IKKbeta. We hypothesized that ischemic preconditioning (IPC) reduces acute renal damage following I/R injury by inhibiting activation of IKKbeta. As neutrophil gelatinase-associated lipocalin (NGAL), an early predictive biomarker of acute kidney injury, is regulated by NF-kappaB, we approached the relationship between NGAL and IKKbeta.', 'Thirty male Sprague-Dawley rats were randomly divided into 3 groups after right kidney nephrectomy. Group A rats were sham-operated controls. Group B rats were 45-min ischemic in the left renal artery while Group C rats were pre-treated with 3 cycles of 2-min ischemia and 5-min reperfusion. All the rats were sacrificed at 24 h after reperfusion. We harvested kidneys and serum to do further analysis, including histological and functional parameters, expressions of NGAL and IKKbeta in renal tissues.', 'Compared with rats subjected to I/R injury, pre-treated rats had a significant decrease in serum creatinine level (Scr) and tubulointerstitial injury scores (Scr, 86.79 +/- 12.98 vs. 205.89 +/- 19.16 mircomol/l, p < 0.01; tubulointerstitial injury scores, 1.3 +/- 0.48 vs. 3.8 +/- 0.79, p < 0.01). In addition, expressions of IKKbeta (0.95 +/- 0.21 vs. 1.74 +/- 0.17, p < 0.05) and NGAL (1.71 +/- 0.032 vs. 2.66 +/- 0.078, p < 0.05) at renal tubule in pre-treated rats were attenuated significantly compared with rats subjected to ischemia-reperfusion injury. Moreover, our study showed that IKKbeta and NGAL were in positive correlation (R = 0.965 > R(0.01)(30) = 0.448, p < 0.01).",
            "output": [
                "Does ischemic preconditioning attenuate renal ischemia-reperfusion injury by inhibiting activation of IKKbeta and inflammatory response?"
            ]
        },
        {
            "id": "task847-170ba2aaba2641d4a23604f48addad4b",
            "input": "Decreased performance status, comorbidities, and disease natural history may erode enthusiasm for soft tissue sarcoma (STS) resection in elderly patients. Consequently, we evaluated the outcome of elderly patients amenable to complete surgical resection treated at a single institution.', 'Prospectively accrued data were used to identify patients with primary STS age >or=65 years (n = 325) who underwent complete macroscopic resection at our institution (1996-2007). Univariable and multivariable analyses were performed to identify prognostic factors.', 'Median age at presentation was 72 years; 179 patients (55.1%) had associated comorbidities with an ASA score of >or=3. Extremity was the most common site (57.1%; n = 186), undifferentiated pleomorphic sarcoma the most common histology (60.4%; n = 197); 232 (71.2%) were high grade, 222 (68.3%) were >5 cm. Thirty-day postoperative mortality was 0.9% (n = 3); overall complication rate was 30.7% (n = 100), and mean postoperative hospital stay was 9 days (range, 1-84). Estimated median survival was 96 months, 5-year disease-specific survival (DSS) was 63%. Multivariable analysis identified age >or=75 year (HR = 2.03), tumor size: 5-15 vs <5 cm (HR = 3.54), or >15 vs <5 cm (HR = 10.33), and high-grade (HR = 5.53) as significant independent adverse prognostic factors. Compared with patients aged 65-74 years, older patients had more high grade tumors (P = .04), received chemotherapy less often (P < .0001), developed different patterns of recurrence (P < .05), and exhibited a shorter median survival (70 months; P = .05).",
            "output": [
                "Is complete soft tissue sarcoma resection a viable treatment option for select elderly patients?"
            ]
        },
        {
            "id": "task847-a81ecd0db7ba49e1979bb006e0ea8782",
            "input": "Triptolide (TPT), a component of the Chinese herb Triptergium wilfordii, has potent immunosuppressive and anti-inflammatory activity and is used clinically in recipients of kidney transplantation.', 'This work aimed to investigate the effect of TPT on the differentiation of regulatory T lymphocytes (Tregs) from CD4+ cells in rats.', 'MACS-purified rat CD4+ cells were costimulated with anti-CD3 and anti-CD28 in the presence of TGF-beta to induce the expression of FoxP3, which was detected by flow cytometry. TPT and cyclosporine A (CsA) were separately added into the cultures to observe the effect on the expression of FoxP3. Kidney transplantation was performed in rats that either received no treatment or were treated with TPT after transplantation.', 'TPT treatment enhanced the expression of FoxP3 in CD4+ cells, whereas CsA inhibited the FoxP3 expression. In the rat kidney transplantation model, the recipient rats treated with TPT survived longer than the control rats (18-19.83 vs 6.83 days, P<0.05). Meanwhile, the FoxP3+ T cells in the spleens of treated rats were higher than those from the untreated rats (12.4% vs 4.7%, P<0.05).",
            "output": [
                "Does triptolide promote generation of FoxP3+ T regulatory cells in rats?"
            ]
        },
        {
            "id": "task847-3a48704b58b646f38938a34115b491ff",
            "input": "A Roux-en-Y hepaticojejunostomy (HJ) is usually performed during live donor liver transplantation (LDLT) when a duct-to-duct reconstruction is not possible. However, direct anastomosis of the bile duct to the duodenum (hepaticoduodenostomy [HD]) is an alternative technique for biliary repair that has been previously used for conventional biliary surgery and at our center for cadaveric liver transplant. We provide the first evidence that HD is an alternative technique for biliary reconstruction in LDLT.', 'We performed a total of 71 LDLT between 2002 and 2008. An end-to-end anastomosis was used in 30 patients. Forty-one patients had a biliary enteric anastomosis in which seven were reconstructed with an HD. Accessory ducts were fashioned into a common duct or implanted into the duodenum separately.', 'There were no patient deaths or retransplants in a follow-up period that ranged from 90 to 771 days after surgery. One patient was diagnosed with cholangitis that responded to intravenous antibiotics and removal of the stent by endoscopy.",
            "output": [
                "Is hepaticoduodenostomy an alternative to Roux-en-Y hepaticojejunostomy for biliary reconstruction in live donor liver transplantation?"
            ]
        },
        {
            "id": "task847-2b2d00924b034a9ebd38bd7fc400d365",
            "input": "The reduction in renal transplant rejection rates achieved over the last 20 years have not translated into a commensurate improvement in long-term graft survival. Cyclosporine has been central to immunosuppressive regimens throughout this period but its effect on long-term transplant outcomes remains unclear.', 'This randomized controlled trial allocated first cadaveric renal transplant recipients in seven centers around Australia to three immunosuppressive regimens: azathioprine and prednisolone (AP), long-term cyclosporine alone (Cy), or cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement (WDL).', 'Between 1983 and 1986, 489 patients were randomized with 98% follow-up to a median of 20.6 years. Mean graft survival (censoring deaths) was superior in the WDL group (14.8 years) when compared with both AP (12.4 years, P=0.01 log-rank test) and Cy (12.5 years, P=0.01 log-rank test) groups by intention-to-treat. Without death censoring, graft survival with WDL was superior to AP (9.5 years vs. 6.7 years, P=0.04) and of borderline superiority to Cy (9.5 years vs. 8.5 years, P=0.06). Patient survival was not different between the three groups. Renal function was superior in AP (at 1, 10, and 15 years posttransplant) and WDL (at 1, 5, 10, 15, and 20 years) groups when compared with Cy.",
            "output": [
                "Does cyclosporine withdrawal improve long-term graft survival in renal transplantation?"
            ]
        },
        {
            "id": "task847-f908189160304edba598006a7d83f337",
            "input": "Fulvestrant is a pure anti-estrogen hormoal agent formally lacking any estrogen-agonist activity. We analyze the effect(s) of fulvestrant treatment on estrogen target systems in hormoe-sensitive advanced breast cancer patients.', 'Patients received a median of five fulvestrant injections (range 3-19). We observed a partial response in one patient, disease stability in 21 and disease progression in 29 patients with a clinical benefit of 43.2% and a median time to progression of 5 [range 3-20] mo. Total cholesterol levels significantly decreased during treatment (219.8 +/- 45.3 vs. 201.4 +/- 42.1 mg/dl; p = 0.0054) together with LDL-cholesterol (129.7 +/- 41.39 vs. 112.3 +/- 37.1 mg/dl; p = 0.018). HDL-cholesterol and triglycerides did not show significant changes. Reduction of total and LDL-cholesterol was independent from last hormoal treatment or treatment duration. All coagulation indices and mean endometrial mucosa thickness value did not vary.', 'Fifty-one patients [median age 65 (range 48-82) y] were enrolled. All patients received previous hormoal treatments, with 90.2% receiving > or =2 courses. Last hormoal treatment was exemestane, letrozole, anastrozole and other in 30-10-7-4/51 patients respectively. Median withdrawal time was 18 d (range 3-1456). Complete fasting lipid blood profile and coagulation indices were assessed before fulvestrant administration, every 3 mo and at discontinuation time. Endometrial mucosa thickness was evaluated before fulvestrant administration and at end-study time.",
            "output": [
                "Is fulvestrant treatment associated with cholesterol plasma level reduction in hormone-receptor-positive metastatic breast cancer patients?"
            ]
        },
        {
            "id": "task847-79fa077460f14fb0804590c8ea56ff19",
            "input": "Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder that frequently presents with neurologic involvement. However, the yield and prognostic value of acute brain neuroimaging in patients with TTP has not been studied. Our aim was to evaluate brain imaging findings in consecutive patients with TTP and assess their impact on prognosis.', 'We retrospectively collected clinical, laboratory, and neuroradiologic information in 47 episodes of acute TTP studied with brain imaging at our medical center between 1997 and 2007. Head CT and brain MRI were evaluated independently by 2 investigators. We then performed statistical analysis to determine whether the presence of acute lesions on brain imaging was associated with worse functional outcome as assessed by the modified Rankin score upon discharge and long-term follow-up.', 'Ten patients (25%) of those who had a head CT had acute changes, half of them indicating posterior reversible encephalopathy syndrome (PRES). Most cases studied with brain MRI had acute changes (82%). More than half of those had evidence of PRES (48%). Atypical variants of PRES were seen in 2 patients with isolated basal ganglia involvement. Acute ischemia and hemorrhage were uncommon. Most patients with acute changes on brain imaging recovered favorably, and radiologic lesions were not associated with worse functional outcome.",
            "output": [
                "Are brain lesions most often reversible in acute thrombotic thrombocytopenic purpura?"
            ]
        },
        {
            "id": "task847-af4e550777f24cac87b71bb0dbfa7726",
            "input": "Spondylarthropathies (SpA) are characterized by abnormal immune responses including T cell activation. Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses. A soluble form of CTLA-4 (sCTLA-4), resulting from an alternative splicing, has been identified and was found increased in several autoimmune diseases. Here, we evaluated circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA. Intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL) were also studied.', 'Sera from 165 patients with SpA were evaluated for sCTLA-4 measurements. Results were compared with those from 71 patients with rheumatoid arthritis (RA) and 88 healthy subjects. In 32 patients with SpA, 22 patients with RA and 15 healthy controls, we analyzed the intracellular CTLA-4 expression in CD4+ T cells, CD8+ T cells, activated (HLA-DR+Foxp3-) CD4+ T cells, CD4+ regulatory (CD25+Foxp3+) T cells and in CD3 negative cells by flow cytometry. Expression of the full length (coding for membrane CTLA-4) and spliced form (coding for sCTLA-4) of CTLA-4 transcripts in PBL were analyzed by quantitative real-time polymerase chain reaction (QRT-PCR).', 'High levels of sCTLA-4 were found in the SpA group compared to the RA group and healthy controls (P < 0.0001). Soluble CTLA-4 serum levels strongly correlated with clinical index of disease activity BASDAI (r = 0.42, P < 0.0001) and C-reactive protein (CRP) levels (r = 0.17, P = 0.037). In contrast to RA patients, SpA patients did not exhibit changes in intracellular CTLA-4 expression in the different PBL subsets tested. Finally, the SpA group showed a preferential expression of the spliced CTLA-4 mRNA (P = 0.0014) in PBL.",
            "output": [
                "Does increased production of soluble CTLA-4 in patients with spondylarthropathies correlate with disease activity?"
            ]
        },
        {
            "id": "task847-4c58fe78765e44aeabbe5417ad3fb3f9",
            "input": "Although current molecular clock methods offer greater flexibility in modelling evolutionary events, calibration of the clock with dates from the fossil record is still problematic for many groups. Here we implement several new approaches in molecular dating to estimate the evolutionary ages of Lacertidae, an Old World family of lizards with a poor fossil record and uncertain phylogeny. Four different models of rate variation are tested in a new program for Bayesian phylogenetic analysis called TreeTime, based on a combination of mitochondrial and nuclear gene sequences. We incorporate paleontological uncertainty into divergence estimates by expressing multiple calibration dates as a range of probabilistic distributions. We also test the reliability of our proposed calibrations by exploring effects of individual priors on posterior estimates.', 'According to the most reliable model, as indicated by Bayes factor comparison, modern lacertids arose shortly after the K/T transition and entered Africa about 45 million years ago, with the majority of their African radiation occurring in the Eocene and Oligocene. Our findings indicate much earlier origins for these clades than previously reported, and we discuss our results in light of paleogeographic trends during the Cenozoic.",
            "output": [
                "Does integration of Bayesian molecular clock methods and fossil-based soft bounds reveal early Cenozoic origin of African lacertid lizards?"
            ]
        },
        {
            "id": "task847-5f1be3b578264b8a8bb029c7cd3639bd",
            "input": "The heterotrimeric G protein alpha-subunit G(s)alpha links receptors to stimulation of cAMP/protein kinase A signaling, which inhibits skin fibroblast proliferation and collagen synthesis. We now describe the development of fibrous tumors in mice with heterozygous disruption of the Gnas gene, which encodes G(s)alpha and other gene products.', 'Disruption of Gnas exon 2 on either the maternal or paternal allele (Gnas(E2-/+)) results in fibromas or angiofibromas on the ears, paws and tail beginning at 4 months of age. The tumors were composed of fibroblastic cell proliferation with collagen and elastin deposition and calcification, and seemed to be associated with mechanical skin damage. The presence of calcification was associated with greater amounts of matrix metalloproteinase-2, suggesting an association between calcium deposition and extracellular matrix degradation. Osteoblast-specific markers were absent, consistent with the calcification not being secondary to ossification. Molecular studies showed that the tumors were not associated with deletion of the wild-type allele, making it unlikely that these tumors resulted from homozygous loss of G(s)alpha.",
            "output": [
                "Does gNAS haploinsufficiency lead to subcutaneous tumor formation with collagen and elastin deposition and calcification?"
            ]
        },
        {
            "id": "task847-36f16d2784e143209bf5f819f1a61c54",
            "input": "In CV-1 cells, shuttling from cytoplasm to nucleus of the nuclear thyroid hormone receptor-beta1 (TRbeta1, TR) is shown in this report to be regulated by extracellular thyroid hormone at a hormone receptor on cell surface integrin alphav3.', 'The receptor was introduced into cells as a GFP-TR1 chimera and intracellular movement of the receptor was monitored by confocal microscopy of cells treated with L-thyroxine (T(4)).",
            "output": [
                "Is cytoplasm-to-nucleus shuttling of thyroid hormone receptor-beta1 ( Trbeta1 ) directed from a plasma membrane integrin receptor by thyroid hormone?"
            ]
        },
        {
            "id": "task847-870921b15d7d454ba887a20e29b70ac0",
            "input": "Hostile neck anatomy is assumed to be associated with increased surgical risk for patients undergoing carotid endarterectomy (CEA) and is often considered a reason to choose carotid stenting or medical management. This retrospective case-control study evaluated whether, and how much, anatomically hostile necks represent a condition of higher surgical risk of early and late mortality and major or minor morbidity.', 'The data for 966 homogeneous CEA patients was prospectively entered in a computer database. Seventy-seven had a hostile neck anatomy due to previous oncologic surgery or neck irradiation, restenoses after CEA, high carotid bifurcation, or bull-like and inextensible neck. A case-control matched-pair cohort study considered sex, age (5-year intervals), and year of operation. Regional anesthesia was used for all operations for atherosclerotic stenosis >or=70%, conforming to the European Carotid Surgery Trial (ECST) in symptomatic and asymptomatic patients, at a single center and by one surgeon or under his direct supervision.', 'The hostile neck patients and the control group were matched for age, sex, carotid-related symptoms, degree of stenoses, and main risk factors for cardiovascular diseases. Intraoperative variables were substantially equivalent in the two groups; however, procedure length and clamping time were, respectively, about 22 minutes (P = .0001) and 7 minutes longer (P = .01) in the hostile neck group. Rates of postoperative mortality and neurologic events were equivalent. Peripheral nerve lesions were multiple and significantly more frequent in the hostile neck patients (21% with >or=1 cranial nerve lesion vs 7% of controls, P = .03), yet all were transient and limited to a few months. The subgroups of patients with hostile neck, restenoses, and bull-like inextensible necks required the longest operative and clamping time, and those with bull-like and high bifurcation had the most frequent cranial nerve dysfunctions. At the respective follow-up of 47 and 45 months, survival curves (P = .48) and the incidence of restenoses and fatal and nonfatal strokes were similar (5 and 4, respectively).",
            "output": [
                "Does the hostile neck increase the risk of carotid endarterectomy?"
            ]
        },
        {
            "id": "task847-537e06ecb25f4e1f944ce1cb3c483b47",
            "input": "Licorice has been used to treat many ailments including cardiovascular disorders in China for long time. Recent studies have shown that the cardiac actions of licorice have been attributed to its active component, glycyrretinic acid (GA). However, its mechanism remains poorly understood.', 'The effects of GA on the cardiac sodium currents (I(Na)), L-type calcium currents (I(Ca,L)) and hyperpolarization-activated inward currents (I(f)) were investigated.', 'Human isoforms of wild-type and DeltaKPQ-mutant type sodium channels were expressed in Xenopus oocytes, and the resulting currents (peak and late I(Na)) were recorded using a two-microelectrode voltage-clamp technique. A perforated patch clamp technique was employed to record I(Ca,L) and I(f) from isolated rabbit sinoatrial node pacemaker cells.', 'GA inhibited peak I(Na) (33% at 90 microM) and late I(Na) (72% at 90 microM), but caused no significant effects on I(Ca,L) and I(f).",
            "output": [
                "Does glycyrretinic acid block cardiac sodium channels expressed in Xenopus oocytes?"
            ]
        },
        {
            "id": "task847-de6969adb82a48ce8137634a6152affd",
            "input": "Depressed mood has been prospectively associated with hypertension. Altered ANS function, as reflected in poor CV recovery, may be one mechanism that underlies this relationship.', 'The purpose of this study was to investigate the relationship between depressed mood and cardiovascular recovery following a standard mental stress task in healthy young women.', 'Depressed mood was assessed in 63 young women. Cardiovascular data were collected during a 5-min baseline period, 5-min public speaking stress task, and 15-min recovery period.', 'Depressed mood accounted for 9.6% of the variation in HR reactivity (F(1,58) = 6.513, p = 0.013) and 4.5% of DBP recovery (F(1,58) = 4.538, p = 0.037).",
            "output": [
                "Is depressed affect associated with poorer cardiovascular recovery in young women following a mental stressor?"
            ]
        },
        {
            "id": "task847-3c39d717115543ea9daa7d851bad012b",
            "input": "Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mechanisms responsible for reverse rate-dependent drug effects.', 'Action potentials were recorded from multicellular canine ventricular preparations and isolated cardiomyocytes, at cycle lengths (CLs) varying from 0.3 to 5 s, using conventional sharp microelectrodes. APD was either modified by applying inward and outward current pulses, or by superfusion of agents known to lengthen and shorten APD. Net membrane current (I(m)) was calculated from action potential waveforms. The hypothesis that RRD may be implicit in the relationship between I(m) and APD was tested by numerical modelling. Both drug-induced lengthening (by veratrine, BAY-K 8644, dofetilide, and BaCl(2)) and shortening (by lidocaine and nicorandil) of action potentials displayed RRD, i.e. changes in APD were greater at longer than at shorter CL. A similar dependency of effect on CL was found when repolarization was modified by injection of inward or outward current pulses. I(m) measured at various points during repolarization was inversely proportional to APD and to CL. Model simulations showed that RRD is expected as a consequence of the non-linearity of the relationship between I(m) and APD.",
            "output": [
                "Is reverse rate dependency an intrinsic property of canine cardiac preparations?"
            ]
        },
        {
            "id": "task847-091e4fbdb1a84447bc006e6e1348ce15",
            "input": "previous studies examining the relationship between socioeconomic status and telomere length showed conflicting results, one study finding shorter telomere length in subjects with lower socioeconomic status and one showing no relationship.', 'cross-sectional study.', 'community-living elderly Chinese in Hong Kong.', 'this study examines the relationship between self-rated social economic status and telomere length in Hong Kong Chinese men and women aged 65 years and over living in the community.', 'information was collected from 958 men and 978 women regarding possible confounding factors such as the presence of chronic diseases, smoking, physical activity level, dietary intake and body mass index. Telomere length was measured by quantitative PCR.', 'in men only, after adjustment for age and other confounding factors, a higher ranking in community standing was associated with shorter telomere length.",
            "output": [
                "Do older men with higher self-rated socioeconomic status have shorter telomeres?"
            ]
        },
        {
            "id": "task847-1b0a5cbf596440cfaa87a91dbea4f2fa",
            "input": "Sleep disturbance is the primary clinical morbidity of restless legs syndrome (RLS). To date, sleep disturbance in RLS has been measured in (1) clinical samples with polysomnography (PSG) or (2) population-based samples by self-report. The objective of this study was to analyze sleep by PSG in a population-based sample with symptoms of RLS.', 'Cross-sectional observational study.', 'Community-based.', '3433 older men and women.', 'None.', 'RLS was evaluated using an 8-item self-administered questionnaire based on NIH diagnostic criteria and required symptoms occurring > or = five times per month and associated with at least moderate distress. Health-related quality of life (HRQOL) was determined using the SF-36. Unattended, in-home PSG was performed. Data were assessed using general linear models with adjustment for demographic, health-related variables, and apnea-hypopnea index (AHI). Subjects with RLS had longer adjusted mean sleep latency (39.8 vs 26.4 min, P < 0.0001) and higher arousal index (20.1 vs 18.0, P = 0.0145) than those without RLS. Sleep latency increased progressively as the frequency of RLS symptoms increased from 5-15 days per month to 6-7 days per week. No differences in sleep stage percentages were observed between participants with and without RLS. Subjects with RLS also reported poorer HRQOL in all physical domains as well as in the Mental Health and Vitality domains.",
            "output": [
                "Does polysomnographic and health-related quality of life correlate of restless legs syndrome in the Sleep Heart Health Study?"
            ]
        },
        {
            "id": "task847-cb1399c5d1034de1a96e6b3bf62b90ab",
            "input": "Plasma VEGF levels increase after minimally invasive colorectal resection (MICR) and remain elevated for 2-4 weeks. VEGF induces physiologic and pathologic angiogenesis by binding to endothelial cell (EC) bound VEGF-Receptor-1 (VEGFR1) and VEGFR2. Soluble forms of these receptors sequester plasma VEGF, decreasing the amount available to bind to EC-bound receptors. Ramifications of surgery-related plasma VEGF changes partially depend on plasma levels of sVEGFR1 and sVEGFR2. This study assessed perioperative sVEGFR1 and sVEGFR2 levels after MICR in patients with colorectal cancer.', 'Forty-five patients were studied; blood samples were taken from all patients preoperatively (preop) and on postoperative days (POD) 1 and 3; in most a fourth sample was drawn between POD 7-30. Late samples were bundled into two time points: POD 7-13 and POD 14-30. sVEGFR1 and sVEGFR2 levels were measured via ELISA. sVEGFR2 data are reported as mean +/- SD and were assessed with the paired samples t test. sVEGFR1 data were not normally distributed. They are reported as median and 95% confidence interval (CI) and were assessed with the Wilcoxon signed-Rank test (p < 0.05).', 'Preoperatively, the mean plasma sVEGFR2 level (7583.9 pg/ml) was greater than the sVEGFR1 result (98.3 pg/ml). Compared with preop levels, sVEGFR2 levels were significantly lower on POD 1 (6068.2 pg/ml, +/-2034.5) and POD 3 (6227.6 pg/ml, +/-2007.0), whereas sVEGFR1 levels were significantly greater on POD 1 (237.5 pg/ml; 95% CI, 89.6-103.5), POD 3 (200.2 pg/ml; 95% CI, 159-253), and POD 7-13 (102.9 pg/ml; 95% CI, 189.7-253). No differences were found on POD 7-13 for sVEGFR2 or POD 14-30 for either protein.",
            "output": [
                "Is minimally invasive colon resection for malignant colonic conditions associated with a transient early increase in plasma sVEGFR1 and a decrease in sVEGFR2 levels after surgery?"
            ]
        },
        {
            "id": "task847-0787ced97d064d4893d023f4c940599d",
            "input": "Hepatocholangiocarcinoma (HCC-CC) is a rare primary liver cancer. Its long-term prognosis is still not well-defined. Results from the Eastern and Western literature have been conflicting and no conclusions can be drawn. The aim of the present study was to review the long-term outcome of curative hepatectomy for HCC-CC.', 'Prospectively collected data from December 1991 to 2006 recording patients with primary liver cancer receiving curative hepatectomy were reviewed. Twenty-five patients, 16 men and 9 women with a median age of 48 years, all ethnic Chinese, had HCC-CC. Their long-term outcome of resection was analyzed and compared to that of patients with cholangiocarcinoma (CC) or hepatocellular carcinoma (HCC).', 'The HCC-CC patients had a median tumor size of 7.5 cm. Five of them developed postoperative complications. The median follow-up period was 25 months. All of the patients developed recurrence. The median overall survival was 25.2 months. The HCC-CC and CC groups had significantly worse overall survival than the HCC group (HCC versus HCC-CC, p = 0.012; HCC versus CC, p = 0.001) whereas between them there was no significant difference (p = 0.822). As for disease-free survival, there was no significant difference between the three groups; the median disease-free survival for HCC-CC patients was 13.5 months; that for CC patients, 16.1 months; and that for HCC patients, 19.0 months. All HCC-CC patients died within 120 months of primary surgery.",
            "output": [
                "Do an update on long-term outcome of curative hepatic resection for hepatocholangiocarcinoma?"
            ]
        },
        {
            "id": "task847-fda2f8b3bd944018a85d582d94d5c967",
            "input": "Restless legs syndrome (RLS) is a neurological condition that is characterized by the irresistible urge to move the legs and is very common. In the last decade, much attention has been focused on RLS, given its high occurrence, underdiagnosis, and impact on quality of life.', 'To determine the frequency of RLS in a neurologic-psychiatric outpatient clinic.', 'We interviewed patients attending a private neurological outpatient clinic, using a standardized validated questionnaire, and an additional phone interview to confirm diagnosis.', 'Of approximately 800 people attending the clinic, the questionnaire was answered by 238 subjects (168 females). Fifteen percent of respondents were affected by RLS and none had been diagnosed before. Most patients had a severe form that probably required treatment.",
            "output": [
                "Is [ Restless legs syndrome highly underdiagnosed in a neurologic-psychiatric outpatient clinic ]?"
            ]
        },
        {
            "id": "task847-1bd29824652d40549e9e6dc716deceb0",
            "input": "Coinfection with hepatitis C virus (HCV) is present in one-third of all human immunodeficiency virus (HIV)-infected individuals in the United States and is associated with rapid progression of liver fibrosis and poor response to pegylated interferon (IFN) and ribavirin. In this study we examined gene expression profiles in peripheral blood mononuclear cells (PBMCs) from different groups of individuals who are monoinfected or coinfected with HIV and HCV. Data showed that HIV and HCV viremia up-regulate genes associated with immune activation and immunoregulatory pathways. HCV viremia is also associated with abnormalities in all peripheral immune cells, suggesting a global effect of HCV on the immune system. Interferon-alpha-induced genes were expressed at a higher level in PBMCs from HIV-infected individuals. HCV and HIV infections leave distinct profiles or gene expression of immune activation in PBMCs. HIV viremia induces an immune activated state; by comparison, HCV infection induces immunoregulatory and proinflammatory pathways that may contribute to progression of liver fibrosis.",
            "output": [
                "Do human immunodeficiency virus and hepatitis C infections induce distinct immunologic imprints in peripheral mononuclear cells?"
            ]
        },
        {
            "id": "task847-00b7541786f846ee936615df8683dd93",
            "input": "The purpose of this study was to examine risk of nursing home (NH) placement among older adults receiving publicly funded home and community-based services (HCBS) or assisted living (AL) and to explore whether these settings of care modify the relationship between dementia and risk of NH placement.', 'The sample consisted of dually eligible Medicare and Medicaid beneficiaries age 65 and older who received HCBS (n = 1630) or resided in AL (n = 836) in Florida between July 1999 and June 2000. Cox proportional hazards regression was used to estimate risk of NH placement over a 5-year study period and to test the interaction of setting of care by dementia status.', 'In all, 15% of HCBS participants were placed in a NH compared to 26% of AL participants. As indicated by a significant interaction term in the regression model, setting of care modified the relationship between dementia and NH placement (HR = 0.45, CI = 0.31-0.66). In post hoc analyses stratified by setting of care, dementia was associated with a 50% increased risk of NH placement from HCBS (HR = 1.50, CI = 1.12-2.02) but was not associated with placement from AL (HR = 0.86, CI = 0.63-1.16).",
            "output": [
                "Does setting of care modify risk of nursing home placement for older adults with dementia?"
            ]
        },
        {
            "id": "task847-a623f8ecd33a4de5ae34b3a7fa02957e",
            "input": "The aim of this study was to investigate the influence of low iron availability on biofilm formation and adherence to HEp-2 cells of enteroaggregative Escherichia coli (EAEC) strains isolated from diarrhoea cases.', 'The ability of EAEC to form biofilm on a plastic surface was evaluated quantitatively and qualitatively after 3 and 18 h of incubation of strains with or without the iron chelator 2,2-dipyridyl. When submitted to low iron conditions, prototype EAEC 042 strain showed a decrease in biofilm formation. Conversely, an increase in biofilm formation was observed for the clinical EAEC strains cultured in restricted iron condition. Moreover, the reduction of iron concentration inhibited the aggregative adherence to HEp-2 cells of all EAEC strains tested. However, all effects promoted by iron chelation were suppressed by thiourea.",
            "output": [
                "Does iron-limited condition modulate biofilm formation and interaction with human epithelial cells of enteroaggregative Escherichia coli ( EAEC )?"
            ]
        },
        {
            "id": "task847-cf3be727607141e58b2e33092457235d",
            "input": "To determine, within the UK, the stage and grade of prostate cancers that would be found through population-based prostate specific antigen (PSA) testing and biopsy.', \"In the 'Prostate Testing for Cancer and Treatment' trial (ProtecT), men aged 50-69 years were recruited from nine cities in the UK and from randomly selected practices of general practitioners. Those with a PSA level of >3 ng/mL were offered a prostate biopsy. Age, PSA, stage and grade at diagnosis of ProtecT participants with cancer were compared with contemporaneous incident cases aged 50-69 years (age-restricted Cancer Registry cases) registered with the Eastern Cancer Registration and Information Centre (ECRIC).\", 'Within ProtecT, 94,427 men agreed to be tested (50% of men contacted), 8807 ( approximately 9%) had a raised PSA level and 2022 (23%) had prostate cancer; 229 ( approximately 12%) had locally advanced (T3 or T4) or metastatic cancers, the rest having clinically localized (T1c or T2) disease. Within ECRIC, 12,661 cancers were recorded over the same period; 3714 were men aged 50-69 years at diagnosis. Men in ProtecT had a lower age distribution and PSA level, and the cancers were of lower stage and grade (P < 0.001 for all comparisons). If population-based PSA testing were introduced in the UK, approximately 2660 men per 100,000 aged 50-69 years would be found to have prostate cancer, compared to current rates of approximately 130 per 100,000. If half of men accepted PSA testing, approximately 160,000 cancers would be found, compared to 30,000 diagnosed each year at present.",
            "output": [
                "Does population-based prostate-specific antigen testing in the UK lead to a stage migration of prostate cancer?"
            ]
        },
        {
            "id": "task847-6fbd01a55aa146aea7099d0c9e6dda8d",
            "input": "The aim of this study was to investigate the suppressive capacity of CD25(+) regulatory T cells on birch allergen-induced T-cell responses during the first birch pollen season after initiation of specific immunotherapy (SIT).', 'CD25(pos) and CD25(neg) T cells were purified from blood of birch-allergic SIT patients and birch-allergic controls, stimulated with birch pollen extract, and analyzed for T-cell proliferation and production of interferon gamma (IFN-gamma), interleukin (IL)-5 and IL-10.', 'We show that allergen-induced proliferation and IFN-gamma production were suppressed equally well by CD25(pos) T cells from SIT patients and controls, while the IL-5 production was not suppressed by either of the groups. IL-10 levels were higher in SIT patients relative to controls only when CD25(neg) and CD25(pos) were cultured together. Furthermore, neither FOXP3 levels nor proportions of CD25(high) T cells were enhanced in SIT patients compared to allergic controls.",
            "output": [
                "Does specific immunotherapy to birch allergen enhance suppression of Th2 cells by CD4 ( + ) CD25 ( + ) regulatory T cells during pollen season?"
            ]
        },
        {
            "id": "task847-f67a5a36efb64f9fb9bd93f25a36dd75",
            "input": "To evaluate the significance of contrast-enhanced ultrasound (CEUS) examination in differential diagnosis of malignant and benign breast lesions.', 'Seventy-one patients with seventy-six breast tumors are selected randomly. CEUS examinations were performed before and after bolus injection of the contrast agent SonoVue (Bracco, Milan, Italy). Specific sonographic quantification software, Qontrast, was adopted to determine the morphology of vessels. Wash-in and wash-out parameters of each lesion were assessed for both procedures.', 'The final histopathological findings distinguished 45 malignant and 31 benign from all of the lesions. Following SonoVue administration different perfusion phases could be identified: early (0-1min), mid (1-4min) and late (4-6min) phases. In the early phase, CEUS identified 91.1% of malignant tumors characterized by a claw-shaped enhancement, while 83.9% of benign tumors had a homogeneous enhancement, with a statistically significant difference between the two enhancement patterns (chi(2)=43.16, P<0.01). Moreover, contrast medium persistence in the late phase was helpful in the identification of benign and malignant tumors (chi(2)=46.88, P<0.01): contrast medium was present in 88.9% of malignant tumors, while in only 9.7% of the benign tumors. The study showed that various parametric imaging color maps for peak intensity and time to peak were mostly suggestive of malignancy, while quite uniform peak intensity and time to peak of color maps were the characteristic of benign tumors. The study also found that malignant lesions presented with a higher maximum intensity signal than benign ones (P<0.05) on the time-intensity curves.",
            "output": [
                "Is contrast-enhanced ultrasound helpful in the differentiation of malignant and benign breast lesions?"
            ]
        },
        {
            "id": "task847-95a0c3a678c74da3bfbd4e2c298850fb",
            "input": "Stathmin, an important cytosolic phosphoprotein, is involved in cell proliferation and motility. This study was performed to elucidate the role of stathmin in the progression of medulloblastoma.', 'The expression of stathmin protein was examined by immunohistochemical staining of tumor sections obtained in 17 consecutive patients with medulloblastoma who underwent resection between 1995 and 2005. Four patients were excluded because they were either lost to follow-up or underwent biopsy sampling only, leaving a total of 13 patients in the study. The stathmin expression was scored according to the immunoreactive fraction of tumor cells, and the level was correlated with various clinicopathological factors.', 'The expression level of stathmin protein was < or = 10% in 9 patients, 11-50% in 1, and > 50% in 3. No staining was seen in the tissues adjacent to the tumors. For comparison, the authors grouped the expression level of stathmin into high (> 50%) and low (< or = 50%). It was found that patients with high expression of stathmin had more frequent tumor dissemination at the time of resection or soon after total excision of the tumor (p = 0.0035), and hence experienced a fulminant course with lower patient survival (p < 0.0001), with an average survival period of 6.7 months (range 2-10 months). The expression level of stathmin did not correlate with patient age, sex, CSF cytological findings, use of adjuvant therapies, Ki 67 index, or risk classification of the tumors according to previously described categories in the literature.",
            "output": [
                "Does high expression of stathmin protein predict a fulminant course in medulloblastoma?"
            ]
        },
        {
            "id": "task847-3fd76c507f904125920a0a63526af8b2",
            "input": "To explore suppression of allograft vasculopathy by transfer of the calcitonin gene-related peptide (CGRP).', 'The descending thoracic aortas from Lewis rats were grafted to the abdominal aortas of F344 rats, and the rats were randomized into 2 groups. A gene construct containing sequences from the adenoviral oncoprotein, the CGRP, and the enhanced green fluorescent protein was transferred into 1 group, and the sequences for the adenoviral oncoprotein and enhanced green fluorescent protein were transferred into a control group. Specimens were harvested at 4 and 8 weeks. Gene transfer was confirmed at fluorescence microscopy of frozen tissue sections, and expression was measured using reverse transcriptase-polymerase chain reaction. We determined the locations and levels of vascular cell adhesion molecule-1 (VCAM-1) and inducible nitric oxide synthase (iNOS) at immunohistochemistry and measured apoptosis.', 'The CGRP gene was expressed only in the CGRP group at 4 weeks. The vascular luminal occlusion score in the CGRP group was lower than in the control group. The apoptotic index of the CGRP group was lower than in the control group only at 4 weeks. The VCAM-1 immunohistochemistry score in the CGRP group was lower than in the control group; however, the iNOS immunohistochemistry score in the CGRP group was lower than in the control group in the intima only at 4 weeks.",
            "output": [
                "Does gene transfer of calcitonin gene-related peptide suppress development of allograft vasculopathy?"
            ]
        },
        {
            "id": "task847-cde60c91617741d4828eee10e058d986",
            "input": "Pulmonary hypertension (PH) is prognosti- cally important in chronic obstructive pulmonary disease (COPD). Since PH only weakly correlates with hypoxemia, other factors must play a role.', 'To investigate whether polymorphisms of the serotonin transporter (5HTT), serotonin-2a receptor (5HTR2a) and endothelial nitric oxide synthetase (eNOS) are related to PH in COPD.', 'In 59 COPD patients who underwent right heart catheterization, 6-min walking distance, NYHA functional class, pulmonary function tests, blood gases and 5HTT, 5HTR2a and eNOS (4ab and T298C) polymorphisms were determined.', 'Forty-nine COPD patients in NYHA functional class III-IV were included. Ten were excluded due to comorbid causes of PH (mainly chronic thromboembolic). PH (mPAP > or =25 mm Hg) was present in 55% and usually mild, but out of proportion (mPAP > or =40 mm Hg) in 12%. Patients with PH had significantly higher frequencies of the 5HTT-L-allele (52%) compared to individuals without PH (36%), and LL homozygote patients had more severe PH. In patients with out-of-proportion PH, the L-allelic frequency was even 75%. We found no association of 5HTR2a and eNOS polymorphism with PH in COPD.",
            "output": [
                "Are genetic polymorphisms of the serotonin transporter , but not the 2a receptor or nitric oxide synthetase , associated with pulmonary hypertension in chronic obstructive pulmonary disease?"
            ]
        },
        {
            "id": "task847-06973573a54449eabbd499dd7622f6b6",
            "input": "Preconditioning neurons with noninjurious hypoxia (hypoxic preconditioning, HPC) or the anesthetic isoflurane (APC) induces tolerance of severe ischemic stress. The mechanisms of both types of preconditioning in the hippocampus require moderate increases in intracellular Ca and activation of protein kinase signaling. The authors hypothesized that the expression of signal transduction genes would be similar after APC and HPC.', 'Hippocampal slice cultures prepared from 9-day-old rats were preconditioned with hypoxia (5 min of 95% nitrogen/5% carbon dioxide) or 1% isoflurane in air/5% carbon dioxide for 1 h. A day later, cultures were subjected to 10 min oxygen and glucose deprivation (simulated ischemia). Intracellular Ca, measured in CA1 neurons at the completion of preconditioning, and cell death in CA1, CA3, and dentate regions was assessed 48 h after simulated ischemia. Message RNA encoding 119 signal transduction genes was quantified with rat complimentary DNA microarrays from pre-oxygen-glucose deprivation samples.', 'Both APC and HPC increased intracellular Ca approximately 50 nm and decreased CA1, CA3, and dentate neuron death by about 50% after simulated ischemia. Many signaling genes were increased after preconditioning, with hypoxia increasing more apoptosis/survival genes (8 of 10) than isoflurane (0 of 10). In contrast, isoflurane increased more cell cycle/development/growth genes than did hypoxia (8 of 14 genes, vs. 1 of 14).",
            "output": [
                "Does expression of signal transduction genes differ after hypoxic or isoflurane preconditioning of rat hippocampal slice cultures?"
            ]
        },
        {
            "id": "task847-85efefe265e94ccc9b5798cb80fdd48d",
            "input": "Cognitive abilities decline with age with large individual variability. Genetic variations have been suggested to be an important source for some of this heterogeneity. Among these variations, those related to the dopaminergic system, particularly the valine(158)methionine polymorphism in catechol-O-methyltransferase (COMTval(158)met), have been implicated in modulating age-related changes in executive function.', 'We studied 75 subjects (age 21-90 years) using functional neuroimaging while they performed a low-level working memory (WM) task to explore the effects of aging, of the COMTval(158)met polymorphism, and their interactions on the physiological patterns of interconnected cortical activity engaged by WM.', 'Our results show that val homozygotes and older subjects showed increased activity in dorsolateral prefrontal cortex (DLPFC) and decreased activity in ventrolateral prefrontal cortex (VLPFC) relative to met homozygotes and younger subjects, respectively. Interestingly, there were also independent effects of the COMTval(158)met polymorphism and age on the strength of connectivity between brain regions within the left prefrontal-parietal network; val homozygotes and older subjects showed greater connectivity between the DLPFC and other brain regions within the network and met homozygotes showed greater connectivity between the VLPFC and other brain regions within the network. Furthermore, the greater functional connectivity strength of DLPFC in val homozygotes relative to met homozygotes was much more pronounced in older adults",
            "output": [
                "Does catechol-O-methyltransferase valine ( 158 ) methionine polymorphism modulate brain networks underlying working memory across adulthood?"
            ]
        },
        {
            "id": "task847-2c52b95f50ef46c8a164179908820ff5",
            "input": "Aedes aegypti is the main mosquito vector of the four serotypes of dengue virus (DENV). Previous population genetic and vector competence studies have demonstrated substantial genetic structure and major differences in the ability to transmit dengue viruses in Ae. aegypti populations in Mexico.', 'Population genetic studies revealed that the intersection of the Neovolcanic axis (NVA) with the Gulf of Mexico coast in the state of Veracruz acts as a discrete barrier to gene flow among Ae. aegypti populations north and south of the NVA. The mosquito populations north and south of the NVA also differed in their vector competence (VC) for dengue serotype 2 virus (DENV2). The average VC rate for Ae. aegypti mosquitoes from populations from north of the NVA was 0.55; in contrast the average VC rate for mosquitoes from populations from south of the NVA was 0.20. Most of this variation was attributable to a midgut infection and escape barriers. In Ae. aegypti north of the NVA 21.5% failed to develop midgut infections and 30.3% of those with an infected midgut failed to develop a disseminated infection. In contrast, south of the NVA 45.2% failed to develop midgut infections and 62.8% of those with an infected midgut failed to develop a disseminated infection.",
            "output": [
                "Is the neovolcanic axis a barrier to gene flow among Aedes aegypti populations in Mexico that differ in vector competence for Dengue 2 virus?"
            ]
        },
        {
            "id": "task847-3d9222ec4c7b4e969a2acafc2ff5e4d0",
            "input": "Chronic pancreatitis (CP) and pancreatic cancer (PCa) are characterized by intrapancreatic neuropathic alterations, including increased neural density and hypertrophy, pancreatic neuritis and neural invasion (NI) by cancer cells in PCa. The aim of this study was to identify the influence of these neuropathic changes on the quality of pancreatic innervation, intrapancreatic glia, and visceral pain.', 'Pancreatic nerve fiber qualities were characterized by immunohistochemical visualization of various markers, including those for sympathetic (tyrosine hydroxylase, TH) and cholinergic innervation (choline acetyltransferase, ChAT), as well as the glial transcription factor, Sox10, and the neuroepithelial progenitor cell marker, Nestin, in normal pancreas (NP, n=16), CP (n=20), and PCa (n=20) patients. The neural immunoreactivity scores of these markers were correlated with the severity of intrapancreatic neuropathic changes and with abdominal pain sensation of patients.', 'Pancreatic sympathetic innervation was significantly reduced in CP and PCa, whereas parasympathetic innervation did not show major changes. Nestin neuro-immunoreactivity was stronger, and Sox10-immunoreactivity was weaker in CP and PCa than in NP. Pancreatic sympathetic and cholinergic innervation was noticeably decreased in patients with severe pancreatic neuritis, NI by cancer cells, or abdominal pain. Moreover, the neural immunoreactivity for Sox10 and Nestin also varied with intrapancreatic neuropathic alterations and abdominal pain.",
            "output": [
                "Does pancreatic neuropathy result in `` neural remodeling '' and altered pancreatic innervation in chronic pancreatitis and pancreatic cancer?"
            ]
        },
        {
            "id": "task847-881c2092070e43c1aab62a0536cbad28",
            "input": "We sought to prospectively examine whether childbearing is associated with higher incidence of the metabolic syndrome (MetS) after delivery among women of reproductive age.', 'In 1451 nulliparas who were aged 18-30 years and free of the MetS at baseline (1985-1986) and reexamined up to 4 times during 20 years, we ascertained incident MetS defined by the National Cholesterol Education Program Adult Treatment Panel III criteria among time-dependent interim birth groups by gestational diabetes mellitus (GDM): (0 [referent], 1 non-GDM, 2+ non-GDM, 1+ GDM births). Complementary log-log models estimated relative hazards of the MetS among birth groups adjusted for race, age, and baseline and follow-up covariates.', 'We identified 259 incident MetS cases in 25,246 person-years (10.3/1000 person-years). Compared with 0 births, adjusted relative hazards (95% confidence interval [CI]) were 1.33 (95% CI, 0.93-1.90) for 1 non-GDM, 1.62 (95% CI, 1.16-2.26) for 2+ non-GDM (P trend = .02), and 2.43 (95% CI, 1.53-3.86) for 1+ GDM births.",
            "output": [
                "Is childbearing associated with higher incidence of the metabolic syndrome among women of reproductive age controlling for measurements before pregnancy : the CARDIA study?"
            ]
        },
        {
            "id": "task847-a7f52c4d82f345868d7754ead39bd320",
            "input": "Evidence of multiple genetic criteria of mate choice is accumulating in numerous taxa. In many species, females have been shown to pair with genetically dissimilar mates or with extra-pair partners that are more genetically compatible than their social mates, thereby increasing their offsprings' heterozygosity which often correlates with offspring fitness. While most studies have focused on genetically promiscuous species, few studies have addressed genetically monogamous species, in which mate choice tends to be mutual.\", 'Here, we used microsatellite markers to assess individual global heterozygosity and genetic similarity of pairs in a socially and genetically monogamous seabird, the black-legged kittiwake Rissa tridactyla. We found that pairs were more genetically dissimilar than expected by chance. We also identified fitness costs of breeding with genetically similar partners: (i) genetic similarity of pairs was negatively correlated with the number of chicks hatched, and (ii) offspring heterozygosity was positively correlated with growth rate and survival.",
            "output": [
                "Is evidence that pairing with genetically similar mates maladaptive in a monogamous bird?"
            ]
        },
        {
            "id": "task847-7b09fbd17cf04c5d9b89393434514fb0",
            "input": "Chronic venous insufficiency (CVI) results when the veins in the legs no longer pump blood back to the heart effectively. Microparticles (MPs) are small membrane vesicles released by several circulating and vascular cells upon activation or apoptosis.', 'The purpose of this study was to assess the subpopulations of circulating endothelial (EMPs) and platelet microparticles (PMPs) in CVI, and to disclose their contribution in mediating dysfunction of human peripheral venules.', 'Human peripheral venules were explanted during leg surgery on patients with CVI and on control subjects (C); concurrently, blood samples were collected and circulating MPs isolated. The techniques used were: flow cytometry, fluorescence and electron microscopy, myograph technique and western-blotting technique.', 'The results showed that compared with controls, patients with CVI had: (i) a marked elevation of circulating EMPs and PMPs; (ii) a structural modification of the venous wall consisting of activation of endothelial and smooth muscle cells, an abundance of intermediary filaments and synthesis of hyperplasic-multilayered basal lamina; (iii) a significantly altered reactivity of the venous wall, closely associated with EMPs and PMPs adherence; (iv) altered contractile response to noradrenaline, acetylcholine, 5-hydroxytryptamine and KCl, and an impeded relaxation in response to sodium nitroprusside; and (iv) a substantially increased protein expression of tissue factor (TF) and of P-Selectin both in the venular vascular wall and on the surface of EMPs and PMPs.",
            "output": [
                "Is chronic venous insufficiency associated with elevated level of circulating microparticles?"
            ]
        },
        {
            "id": "task847-9ad785e622e54070984a71068f247b32",
            "input": "Defects of the mitochondrial genome (mtDNA) cause a series of rare, mainly neurological disorders. In addition, they have been implicated in more common forms of movement disorders, dementia and the ageing process. In order to try to model neuronal dysfunction associated with mitochondrial disease, we have attempted to establish a series of transmitochondrial mouse embryonic stem cells harbouring pathogenic mtDNA mutations.', 'Transmitochondrial embryonic stem cell cybrids were generated by fusion of cytoplasts carrying a variety of mtDNA mutations, into embryonic stem cells that had been pretreated with rhodamine 6G, to prevent transmission of endogenous mtDNA. Cybrids were differentiated into neurons and assessed for efficiency of differentiation and electrophysiological function.', 'Neuronal differentiation could occur, as indicated by expression of neuronal markers. Differentiation was impaired in embryonic stem cells carrying mtDNA mutations that caused severe biochemical deficiency. Electrophysiological tests showed evidence of synaptic activity in differentiated neurons carrying non-pathogenic mtDNA mutations or in those that caused a mild defect of respiratory activity. Again, however, neurons carrying mtDNA mutations that resulted in severe biochemical deficiency had marked reduction in post-synaptic events.",
            "output": [
                "Are transmitochondrial embryonic stem cells containing pathogenic mtDNA mutations compromised in neuronal differentiation?"
            ]
        },
        {
            "id": "task847-d0a648487b14474486d57b323296576c",
            "input": "No previous study has examined the comorbidity of Irritable Bowel Syndrome (IBS) and Generalized Anxiety Disorder (GAD) in a general population using standardized diagnostic methods.', 'To examine the prevalence, comorbidity and risk correlates of IBS and GAD in a general population.', 'A random community-based telephone survey was conducted. The questionnaire covered symptoms of IBS, GAD, core depressive symptoms, help-seeking behaviour and functional impairment on the Sheehan Disability Scale.', 'A total of 2005 participants completed the interview. The current prevalence of IBS was 5.4% and the 12-month prevalence of GAD was 4%. GAD was five times more common among IBS respondents than non-IBS respondents (OR: 5.84, P < 0.001), whereas IBS was 4.7 times more common among GAD respondents than among non-GAD respondents (OR: 6.32, P < 0.001). Core depressive symptoms (OR: 6.25, P < 0.01) and education level (OR: 5.918, P = 0.021) were risk correlates of GAD among IBS respondents. Comorbid respondents were more impaired than respondents having either disorder alone, but were not more likely to seek professional help than IBS-only respondents.",
            "output": [
                "Is irritable bowel syndrome strongly associated with generalized anxiety disorder : a community study?"
            ]
        },
        {
            "id": "task847-11e99dde16d94650bdc39de3cbc685e8",
            "input": "This study assessed the influence of age on the predictors of bone mineral in men.', 'Middle-age (n = 41, 54 +/- 4 yrs) and older (n = 40, 69 +/- 5 yrs) men underwent grip and knee extensor strength tests, total body dual-energy X-ray absorptiometry with regional analyses and a graded exercise treadmill test.', 'Bone-free lean mass (BFLM) and, to a lesser extent, fat mass (FM) were correlated with bone mineral variables in middle-age men. In older men, BFLM and, to a lesser extent, FM were related to bone mineral content (BMC) at most sites, but inconsistently to bone mineral density (BMD). Knee extensor strength related to bone mineral (BMC and BMD) at most sites in middle-age men, but none in older men. Grip strength inconsistently related to bone mineral in both groups. Aerobic capacity related to bone mineral in middle-age men, but none in older men. In multiple regression, body weight or BFLM predicted bone mineral in middle-age men (R2 = 0.33-0.68) and BMC in older men (R2 = 0.33-0.50). Predictors of BMD were inconsistent in older men.",
            "output": [
                "Does age influence anthropometric and fitness-related predictors of bone mineral in men?"
            ]
        },
        {
            "id": "task847-9092a2095ae24fe1a19db44b2a1bb0d8",
            "input": "We conducted this pooled analysis to assess the prognostic value of pretreatment Quality of Life (QOL) assessments on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).', 'Four hundred twenty patients with advanced NSCLC (stages IIIB with pleural effusion and IV) from six North Central Cancer Treatment Group trials were included in this study. QOL assessments included the single-item Uniscale (355 patients), Lung Cancer Symptom Scale (217 patients), and Functional Assessment of Cancer Therapy-Lung (197 patients). QOL scores were transformed to a 0 to 100 scale with higher scores representing better status and categorized using the sample median or clinically deficient score (CDS, <or=50 versus >50). Cox proportional hazards models stratified by study were used to evaluate the prognostic importance of QOL on OS alone and in the presence of other prognostic factors such as performance status, age, gender, body mass index, and laboratory parameters.', 'Pretreatment QOL accessed by Uniscale was significantly associated with OS univariately (p < 0.0001). Uniscale (p < 0.0001; hazard ratio = 1.6 for the sample median and 2.0 for the CDS categorization) and body mass index were the only significant predictors of OS multivariately. The median survival of patients who had a Uniscale score less than or equal to the CDS (<or=50) was 5.7 versus 11.1 months for the >50 group; and 7.8 versus 13 months for the less than or equal to sample median (<or=83) group and >83 group, respectively. The Lung Cancer Symptom Scale and the Functional Assessment of Cancer Therapy-Lung total scores were not significant predictors of OS.",
            "output": [
                "Is pretreatment quality of life an independent prognostic factor for overall survival in patients with advanced stage non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-8052b546ec254d09831aacb9110bd74c",
            "input": "In order to improve the diagnosis of Bacillus anthracis in environmental samples, we established a DNA microarray based on the ArrayTube technology of Clondiag.', 'Total DNA of a bacterial colony is randomly biotinylated and hybridized to the array. The probes on the array target the virulence genes, the genomic marker gene rpoB, as well as the selective 16S rDNA sequence regions of B. anthracis, of the Bacillus cereus group and of Bacillus subtilis. Eight B. anthracis reference strains were tested and correctly identified. Among the analysed environmental Bacillus isolates, no virulent B. anthracis strain was detected.",
            "output": [
                "Does a DNA microarray facilitate the diagnosis of Bacillus anthracis in environmental samples?"
            ]
        },
        {
            "id": "task847-0f74477c6bf54b0089f466c8b9a30c7b",
            "input": "The aim of this study was to develop an assay system that can quantify the amount of biomass in biofilms formed by different isogenic mutants of an Escherichia coli K-12 strain.', 'The reported assay, which is based on the BacTiter-Glo assay from Promega, uses bioluminescence to detect the intracellular concentration of ATP, which correlates with viable bacterial cell numbers. The quantitative data obtained with this ATP assay were compared to those obtained with the conventional crystal violet assay. As a qualitative control, scanning electron microscopy was performed.",
            "output": [
                "Does a combination of assays reveal biomass differences in biofilms formed by Escherichia coli mutants?"
            ]
        },
        {
            "id": "task847-ec999a4e6405489fafe67f43c779ddb0",
            "input": "Recent studies suggested a role for pro-inflammatory mediators in frontotemporal lobar degeneration (FTLD). The objective of this study was to evaluate the association of functionally active polymorphisms in pro-inflammatory cytokine genes with the occurrence and the clinical features of the disease.', 'Using a case-control study, we compared allelic and genotypic frequencies of several polymorphisms in the interleukin (IL)-1alpha, interleukin (IL)-1beta, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha genes between 110 FTLD patients and 119 healthy controls.', 'No significant association between the examined polymorphisms and the disease was found. However, in comparison with remaining genotypes, patients carrying the T/T genotype of the IL-1beta gene showed a significantly lower age at onset of the disease. In addition, scores of the Frontal Assessment Battery were significantly modified by the IL-6 -174G>C polymorphism.",
            "output": [
                "Do pro-inflammatory cytokine genes influence the clinical features of frontotemporal lobar degeneration?"
            ]
        },
        {
            "id": "task847-4409662f0dc74624bb4bc4c7604047a0",
            "input": "AVE9633 is a new immunoconjugate comprising a humanized monoclonal antibody, anti-CD33 antigen, linked through a disulfide bond to the maytansine derivative DM4, a cytotoxic agent and potent tubulin inhibitor. It is undergoing a phase I clinical trial. Chemoresistance to anti-mitotic agents has been shown to be related, in part, to overexpression of ABC proteins. The aim of the present study was to investigate the potential roles of P-gp, MRP1 and BCRP in cytotoxicity in AVE9633-induced acute myeloid leukaemia (AML).', 'This study used AML cell lines expressing different levels of P-gp, MRP1 or BCRP proteins and twenty-five samples from AML patients. Expression and functionality of the transporter protein were analyzed by flow cytometry. The cytotoxicity of the drug was evaluated by MTT and apoptosis assays.', 'P-gp activity, but not MRP1 and BCRP, attenuated AVE9633 and DM4 cytotoxicity in myeloid cell lines. Zosuquidar, a potent specific P-gp inhibitor, restored the sensitivity of cells expressing P-gp to both AVE9633 and DM4. However, the data from AML patients show that 10/25 samples of AML cells (40%) were resistant to AVE9633 or DM4 (IC(50) > 500 nM), and this was not related to P-gp activity (p-Value: 0.7). Zosuquidar also failed to re-establish drug sensitivity. Furthermore, this resistance was not correlated with CD33 expression (p-Value: 0.6) in those cells.",
            "output": [
                "Is p-gp activity a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines , but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients?"
            ]
        },
        {
            "id": "task847-a883d71f88d9421387a66121369ce7a8",
            "input": "The biliary cast syndrome (BCS) is a frequent problem following liver transplantation. The pathogenesis of this complication is not well understood. Previous research has demonstrated that the soluble form of MICA (sMICA) is significantly higher in patients with chronic liver disease and hepatocellular carcinoma (HCC) than in healthy volunteers. The aim of this study is to investigate the possible involvement of sMICA in the formation of BCS after liver transplantation.', 'Serum soluble MICA was retrospectively evaluated in pre- and post-transplant sera from 133 consecutive primary liver transplant patients and in sera from 88 healthy volunteers using sandwich ELISA. Normal distribution of serum sMICA was described by the data obtained from healthy population and sMICA concentration that was greater than the upper bound 95% normal range was considered as high levels of sMICA. Patient records were reviewed to identify patients who developed BCS.', 'The results demonstrated that 37.6% of patients with end-stage liver diseases had significantly higher pre-transplant serum sMICA than in healthy population. 34.4% of recipients with post-transplant high levels of sMICA developed BCS. In contrast, 17.3% of patients with post-transplant normal levels of sMICA developed BCS. The risk of BCS development is significantly associated with the presence of post-transplant high levels of sMICA (P=0.0365). Further analysis disclosed that patients with decreased post-transplant sMICA following liver transplantation had a lower incidence rate of BCS than those with remained high levels of sMICA after transplantation (10.5% vs. 38.7%, P=0.0302). Furthermore, log-rank test showed that BCS occurrence was significantly associated with dynamic changes of sMICA among different groups (P=0.0188).",
            "output": [
                "Are high levels of soluble Major Histocompatibility Complex class I related chain A ( MICA ) associated with biliary cast syndrome after liver transplantation?"
            ]
        },
        {
            "id": "task847-4ead5dbe74fa4e6caac32fba460acedd",
            "input": "Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) is associated with a decreased incidence of perioperative cardiac complications compared with open repair. However, EVAR is not associated with long-term survival benefit. This study assessed the effect of perioperative asymptomatic cardiac damage after EVAR on long-term prognosis.', \"In 220 patients undergoing elective EVAR, routine sampling for levels of cardiac troponin T and electrocardiography (ECG) were performed on days 1, 3, and 7 during the patient's hospital stay. Elevated cardiac troponin T was defined as serum concentrations >or=0.01 ng/mL. Asymptomatic cardiac damage was defined as cardiac troponin T release without symptoms or ECG changes. The median follow-up was 2.9 years. Survival status was obtained by contacting the Office of Civil Registry.\", 'Release of cardiac troponin T (median, 0.08 ng/mL) occurred in 24 of 220 patients, of whom 20 (83%) were asymptomatic and without ECG changes. Patients with asymptomatic cardiac damage had a mortality rate of 49% [corrected] after 2.9 years vs 15% [corrected] for patients without perioperative cardiac damage (P < .001). Also after adjustment for clinical risk factors and medication use applying multivariate Cox regression analysis, asymptomatic cardiac damage was associated with a 2.3-fold increased risk for death (95% confidence interval, 1.1-5.1). Statin use was associated with a reduced long-term risk for death (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9).",
            "output": [
                "Is perioperative asymptomatic cardiac damage after endovascular abdominal aneurysm repair associated with poor long-term outcome?"
            ]
        },
        {
            "id": "task847-c4763aab63194be8912d4f691cfeb095",
            "input": "Inflammatory responses to vascular injury are key events in vein graft disease and accelerated atherosclerosis, which may result in bypass failure. The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor (CCR)-2 pathway is hypothesized to play a central role. A murine model for vein graft disease was used to study the effect of local application of lentiviral short hairpin RNA (shRNA) targeted against CCR2.', 'A venous interposition was placed into the carotid artery of hypercholesterolemic apolipoprotein E3-Leiden (APOE*3-Leiden) mice to induce vein graft thickening with features of accelerated atherosclerosis. To demonstrate the efficacy of the lentiviral shRNA targeting murine CCR2 (shCCR2) in blocking vein graft disease in vivo, lentiviral shCCR2 or a control lentivirus was used to infect the vein graft locally (n = 8).', 'Vascular CCR2 and MCP-1 messenger RNA expression levels were significantly upregulated during lesion progression in the vein graft. Infection of smooth muscle cells (SMCs) with a lentiviral shRNA targeting shCCR2 completely abolished MCP-1-induced SMC migration and inhibited SMC proliferation in vitro (n = 3 per group). Morphometric analysis of sections of grafts showed a significant 38% reduction in vein graft thickening in the shCCR2-treated mice 4 weeks after surgery (control, 0.42 +/- 0.05 mm(2); shCCR2, 0.26 +/- 0.03 mm(2); P = .007).",
            "output": [
                "Does local lentiviral short hairpin RNA silencing of CCR2 inhibit vein graft thickening in hypercholesterolemic apolipoprotein E3-Leiden mice?"
            ]
        },
        {
            "id": "task847-6a67c69345d44837ae6ae1c2bfb2cc9e",
            "input": "Progress in the management of patients with medically intractable epilepsy is impeded because we do not fully understand why pharmacoresistance happens and how it can be predicted. The presence of multiple seizures prior to medical treatment has been suggested as a potential predictor of poor outcome. In the present study, we used an animal model of temporal lobe epilepsy to investigate whether pharmacoresistant rats differ in seizure frequency from pharmacoresponsive animals.', 'Epilepsy with spontaneous recurrent seizures (SRS) was induced by status epilepticus. Frequency of SRS was determined by video/EEG (electroencephalography) monitoring in a total of 33 epileptic rats before onset of treatment with phenobarbital (PB).', 'Thirteen (39%) rats did not respond to treatment with PB. Before treatment with PB, average seizure frequency in PB nonresponders was significantly higher than seizure frequency in responders, which, however, was due to six nonresponders that exhibited > 3 seizures per day. Such high seizure frequency was not observed in responders, demonstrating that high seizure frequency predicts pharmacoresistance in this model, but does not occur in all nonresponders.",
            "output": [
                "Is high seizure frequency prior to antiepileptic treatment a predictor of pharmacoresistant epilepsy in a rat model of temporal lobe epilepsy?"
            ]
        },
        {
            "id": "task847-41d5a80eb8c94fbe9bc00118b2843a64",
            "input": "Associations between multidrug resistance and the Mycobacterium tuberculosis Beijing genotype have been described mainly in populations with poor tuberculosis (TB) control such as prisons and inner cities, and may reflect shared risk factors rather than a biological association.', 'To study the association between genotype and drug resistance among TB patients in a population with adequate TB control.', 'Three rural districts in Vietnam. The study was performed at the Pham Ngoc Thach Tuberculosis and Lung Disease Hospital, Ho Chi Minh City, and the Tien Giang Provincial Tuberculosis and Lung Disease Hospital, My Tho, Vietnam.', 'Pretreatment sputum specimens were collected for culture, drug susceptibility testing and spoligotyping of all sputum smear-positive pulmonary TB patients consecutively diagnosed over a 3-year period.', 'Beijing genotype infections were observed in 614 of 1744 (35%) patients. Beijing strains were more common among female (adjusted odds ratio [aOR] 1.4, P = 0.005), young (aOR 2.8, P < 0.001) and previously treated patients (aOR 2.4, P < 0.001). The Beijing genotype was associated with any resistance (aOR 3.7, P < 0.001) and multidrug resistance (aOR 6.8, P < 0.001) among new patients, and with any resistance (aOR 2.7, P = 0.005) but not with multidrug resistance (aOR 1.4, P = 0.545) among previously treated patients.",
            "output": [
                "Is the Beijing genotype associated with young age and multidrug-resistant tuberculosis in rural Vietnam?"
            ]
        },
        {
            "id": "task847-a69ce54004354235ab536b77f5ce1515",
            "input": "Human studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that epsilon4 carriers may benefit from regular physical activity.', 'We examined voluntary wheel-running, memory, and hippocampal plasticity in APOE epsilon3 and APOE epsilon4 transgenic mice at 10-12 months of age.', 'Sedentary epsilon4 mice exhibited deficits in cognition on the radial-arm water maze (RAWM), a task dependent on the hippocampus. Six weeks of wheel-running in epsilon4 mice resulted in improvements on the RAWM to the level of epsilon3 mice. Hippocampal brain-derived neurotrophic factor (BDNF) levels were similar in epsilon3 and epsilon4 mice, and after exercise BDNF was similarly increased in both epsilon3 and epsilon4 mice. In sedentary epsilon4 mice, tyrosine kinase B (Trk B) receptors were reduced by 50%. Exercise restored Trk B in epsilon4 mice to the level of epsilon3 mice, and in epsilon4 mice, exercise dramatically increased synaptophysin, a marker of synaptic function.",
            "output": [
                "Does exercise improve cognition and hippocampal plasticity in APOE epsilon4 mice?"
            ]
        },
        {
            "id": "task847-beca7db2190741a9ad2748292a5d29ca",
            "input": "Fatigue contributes directly to anterior cruciate ligament (ACL) injury via promotion of high risk biomechanics. The potential for central fatigue to dominate this process, however, remains unclear. With centrally mediated movement behaviors being trainable, establishing this link seems critical for improved injury prevention. We thus determined whether fatigue-induced landing biomechanics were governed by a centrally fatiguing mechanism.', 'Twenty female NCAA athletes had initial contact (IC) and peak stance (PS) three-dimensional hip and knee biomechanics quantified during anticipated and unanticipated single-leg landings, before and during unilateral fatigue accumulation. To induce fatigue, subjects performed repetitive (n = 3) single-leg squats and randomly ordered landings, until squats were no longer possible. Subject-based dependent factors were calculated across prefatigue trials and for those denoting 100%, 75%, 50%, and 25% fatigue and were submitted to three-way mixed-design analyses of covariance to test for decision, fatigue time, and limb effects.', 'Fatigue produced significant (P < 0.01) decreases in IC knee flexion angle and PS knee flexion moment and increases in PS hip internal rotation and knee abduction angles and moments, with differences maintained from 50% fatigue through to maximum. Fatigue-induced increases in PS hip internal rotation angles and PS knee abduction angles and loads were also significantly (P < 0.01) greater during unanticipated landings. Apart from PS hip moments, significant limb differences in fatigued landing biomechanics were not observed.",
            "output": [
                "Does fatigue-induced ACL injury risk stem from a degradation in central control?"
            ]
        },
        {
            "id": "task847-a3fbda47722845fc8224bc9c940a8145",
            "input": "Total parenteral nutrition (TPN) impairs host immunocompetence, a mechanism possibly underlying the high morbidity of infectious complications in critically ill patients. Our recent study demonstrated TPN to reduce the number and function of hepatic mononuclear cells (MNCs) and to worsen survival after intraportal Pseudomonas challenge in mice. The present study examined the duration of enteral nutrition (EN) needed to reverse TPN-induced changes in hepatic MNCs in a murine model.', 'Male ICR mice (6 weeks) received 5 days of TPN followed by 0 (TPN), 12 (EN12), 24 (EN24), 48 (EN48) or 72 (EN72)h of chow feeding. Control mice (Control) were given chow with intravenous saline infusions for 5 days. After nutritional support, hepatic MNCs were isolated and counted. Lipopolysaccharide (LPS) receptor expressions (CD14 and TLR4/MD2) on Kupffer cells were analyzed by flowcytometry. In addition, TPN, EN12, EN48 and control mice were given intraportal Pseudomonas challenge and survival was monitored.', 'The TPN group was significantly lower in hepatic MNC number and LPS receptor expressions than the Control group. However, EN quickly reversed TPN-induced hepatic impairments in MNC loss within 12h, CD14 expression within 48 h and TLR4/MD2 expression within 24h. Survival of the EN48 group was significantly improved as compared with the TPN and EN12 groups.",
            "output": [
                "Does enteral nutrition rapidly reverse total parenteral nutrition-induced impairment of hepatic immunity in a murine model?"
            ]
        },
        {
            "id": "task847-2c68294e860b4848b14cf87aec88f862",
            "input": "Humans can easily restore a speech signal that is temporally masked by an interfering sound (e.g., a cough masking parts of a word in a conversation), and listeners have the illusion that the speech continues through the interfering sound. This perceptual restoration for human speech is affected by prior experience. Here we provide evidence for perceptual restoration in complex vocalizations of a songbird that are acquired by vocal learning in a similar way as humans learn their language.', \"European starlings were trained in a same/different paradigm to report salient differences between successive sounds. The birds' response latency for discriminating between a stimulus pair is an indicator for the salience of the difference, and these latencies can be used to evaluate perceptual distances using multi-dimensional scaling. For familiar motifs the birds showed a large perceptual distance if discriminating between song motifs that were muted for brief time periods and complete motifs. If the muted periods were filled with noise, the perceptual distance was reduced. For unfamiliar motifs no such difference was observed.",
            "output": [
                "Does stimulus familiarity affect perceptual restoration in the European starling ( Sturnus vulgaris )?"
            ]
        },
        {
            "id": "task847-cc71315f8f574876b80c85b3e80c83d3",
            "input": "Enhanced insulin sensitivity is commonly seen following Roux-en-Y gastric bypass surgery (RYGB) whereas symptomatic hypoglycemia post-RYGB seems to occur infrequently. It is unclear how different plasma glucose and insulin responses are in patients with symptomatic hypoglycemia (SX-RYGB) versus those who remain asymptomatic (ASX-RYGB), nor when compared with non-surgical controls with varying degrees of insulin sensitivity.', 'Plasma glucose and insulin concentrations were determined following a 75-g oral glucose challenge in five groups: symptomatic and asymptomatic patients following RYGB (n = 9 each) and overweight/obese controls, divided into three subgroups (n = 30 each) on the basis of degree of insulin sensitivity measured by the insulin suppression test.', 'SX-RYGB group had higher 30-min glucose after oral glucose compared with the ASX-RYGB group (p = 0.04). The two groups did not differ in peak glucose and insulin concentrations, nadir glucose concentration, or insulin-to-glucose ratio 30 min after oral glucose. These values were significantly different from the three control groups, and peak insulin concentrations post-RYGB were increased at every degree of insulin sensitivity as compared with the control groups.",
            "output": [
                "Is plasma glucose and insulin regulation abnormal following gastric bypass surgery with or without neuroglycopenia?"
            ]
        },
        {
            "id": "task847-e02b8c457dfb4ed5a25c2ee49f70e3cd",
            "input": "To describe the associations between mediators of the somatotropic axis and mortality from sepsis-induced multiple organ dysfunction syndrome in children; and to examine the relationship between immune function and the somatotropic axis in this setting.', 'Retrospective study using banked plasma.', \"Single mixed surgical/medical intensive care unit at a quaternary level children's hospital.\", 'A total of 24 children (n = 17 survivors, 7 nonsurvivors) with severe sepsis or septic shock and dysfunction of >or=2 organ systems.', 'None.', 'Plasma samples were available from days 3, 7, and 14 of multiple organ dysfunction syndrome. Insulin-like growth factor 1 and insulin-like growth factor binding protein 3 levels were measured by chemiluminescence. Immune function was quantified using previously determined ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha production levels and absolute lymphocyte counts. Insulin-like growth factor 1 levels were lower in nonsurvivors compared with survivors (p = .004) with the greatest difference seen on day 14 (25 [25-69] ng/mL vs. 314 [123-582] ng/mL; p = .038). insulin-like growth factor binding protein 3 levels were reduced similarly over time (p = .019). A drop in plasma insulin-like growth factor binding protein 3 level at any time after day 3 of illness resulted in a 35-fold increased odds of death (odds ratio, 35 [1.6-750]; p = .004). Both ex vivo tumor necrosis factor-alpha and absolute lymphocyte count were reduced in nonsurvivors compared with survivors, but these differences occurred earlier (days 3 and 7).",
            "output": [
                "Is failure to recover somatotropic axis function associated with mortality from pediatric sepsis-induced multiple organ dysfunction syndrome?"
            ]
        },
        {
            "id": "task847-f0534d44da6540b59541ef932cef398e",
            "input": "Immune responses are tempered in immunologically privileged sites including the testis. Previous studies have shown that islet transplantation in the testis significantly prolongs islet allograft survival. However, mechanisms underlying testicular immune privilege and intratesticular allograft survival remain unclear.', 'Allogeneic murine islets were transplanted in the testis. Programmed death-1 ligand-1 (PD-L1) expression was detected by immunohistochemstry and real-time polymerase chain reaction. Infiltrating T-cell proliferation was measured by bromodeoxyuridine uptakes, whereas their apoptosis was quantified by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling methods. Transgenic T cells were used to track allospecific memory T-cell generation.', 'We found that programmed death-1 (PD-1):PD-L1 negative costimulation is essential for prolonged survival of intratesticular islet allografts, as blocking PD-L1 or PD-1, but not PD-L2 and cytotoxic T-lymphocyte antigen 4, abrogated long-term survival of intratesticular islet allografts. As controls, blocking PD-1 or PD-L1 did not significantly accelerate the acute rejection of islet allografts transplanted under the renal capsule, a conventional islet-grafting site. We also found for the first time that PD-L1 is constitutively expressed mainly by spermatocytes and spermatids in seminiferous tubules of the testis. Moreover, infiltrating T cells underwent less vigorous proliferation but faster apoptosis in the testis than in the kidney. Blocking PD-1:PD-L1 costimulation largely abolished the suppression of T-cell proliferation and acceleration of T-cell apoptosis. Importantly, testicular immune privilege significantly suppressed the generation and proliferation of donor-specific memory CD8 T cells.",
            "output": [
                "Does interaction of programmed death-1 and programmed death-1 ligand-1 contribute to testicular immune privilege?"
            ]
        },
        {
            "id": "task847-209e3f55730f454a902d92092ba03f2e",
            "input": "This study investigated whether mesenchymal stem cells (MSCs) combined with bone marrow transplantation (BMT), irradiation, or short-term immunosuppressant therapy could prolong composite tissue allotransplant survival in a swine hind-limb model.', 'Heterotopic hind-limb transplantation was performed in outbred miniature swine. Group I (n=5) was the untreated control. Group II (n=3) received MSCs alone (given on days -1, +3, +7, +14, +21). Group III (n=6) received cyclosporine A (CsA days 0 to +28). Group IV (n=4) received preconditioning irradiation (day -1), BMT (day +1), and CsA (days 0 to +28). Group V (n=5) received irradiation (day -1), BMT (day +1), CsA (days 0 to +28), and MSCs (days +1, +7,+14). The expression and localization of CD4/CD25 T cells and MSCs were assessed using flow cytometry and immunohistochemistry.', 'The allografts survival with MSCs alone revealed a significant prolongation, when compared with the controls (P=0.02). Allografts with CsA treatment exhibited delayed rejection. Irradiation and BMT-CsA treatment revealed no significant allograft survival benefit when compared with the CsA treatment group, but graft-versus-host disease (GVHD) was evident. However, combination of MSCs-BMT-CsA treatment demonstrated significant prolongation of allograft survival (>200 days, P<0.001) and no signs of GVHD with the lowest degree of rejection in the allo-skin and interstitial muscle layers. The CD4/CD25 regulatory-like T-cell expression in the circulating blood and allo-skin significantly increased in the MSC-BMT-CsA group. Examination of bromodeoxyuridine-labeled MSCs revealed donor MSC engraftment into the recipient and donor skin and the recipient liver parenchymal tissue.",
            "output": [
                "Do mesenchymal stem cells prolong composite tissue allotransplant survival in a swine model?"
            ]
        },
        {
            "id": "task847-676ee2b16c68492796113a9db100baa8",
            "input": "Potential xenozoonosis is a concern for the clinical application of xenotransplantation. Human cytomegalovirus (HCMV) is one of the most important pathogens in allotransplantation, but the consequences of HCMV cross-species infection of porcine xenografts are unknown. Therefore, we investigated the effects of HCMV infection of porcine endothelial cells (pEC) on cell surface molecule expression and human leukocyte recruitment.', 'Infection of pEC inoculated with untreated, UV-inactivated, or heparin-treated HCMV at a multiplicity of infection (MOI) of 1 was analyzed by immediate early (IE) antigen expression. Cell surface receptor expression was studied by flow cytometry on pEC bulk cultures and differentially on IE-positive and -negative pEC. Adhesion of human leukocytes was tested on pEC monolayers. pEC supernatants were analyzed for cytokine content, chemotactic activity, and stimulatory effect on resting secondary pEC cultures.', 'At day 2 postinfection, IE staining was evident in 10% to 20% of HCMV-infected cells. Cell-surface expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) was upregulated in both IE-negative and -positive fractions of HCMV-infected pEC. In contrast, porcine major histocompatibility complex class I expression was upregulated in IE-negative cells, but reduced in IE-positive cells. The receptor alterations in the IE-negative fraction were mediated by pEC-derived soluble factors. The increased adhesion receptor expression was paralleled by enhanced human leukocyte chemotaxis and adhesion to infected pEC cultures. Pretreatment of HCMV with heparin, but not UV-inactivation, prevented adhesion-receptor modulation and reversed the increased adhesion and chemotaxis.",
            "output": [
                "Does human CMV infection of porcine endothelial cells increase adhesion receptor expression and human leukocyte recruitment?"
            ]
        },
        {
            "id": "task847-1fe28f5b47a444ddaecb3d9da1d96284",
            "input": "The underlying mechanisms of steatosis, the first stage of non-alcoholic fatty liver disease (NAFLD) that is characterized by the accumulation of lipids in hepatocytes, remain unclear. Our study aimed to investigate the hypothesis that cigarette smoke is known to change circulating lipid profiles and thus may also contribute to the accumulation of lipids in the liver.', 'Mice and cultured hepatocytes were exposed to sidestream whole smoke (SSW), a major component of \"second-hand\" smoke and a variety of cellular and molecular approaches were used to study the effects of cigarette smoke on lipid metabolism.', \"SSW increases lipid accumulation in hepatocytes by modulating the activity of 5'-AMP-activated protein kinase (AMPK) and sterol response element binding protein-1 (SREBP-1), two critical molecules involved in lipid synthesis. SSW causes dephosphorylation/ inactivation of AMPK, which contributes to increased activation of SREBP-1. These changes of activity lead to accumulation of triglycerides in hepatocytes.",
            "output": [
                "Does second-hand smoke stimulate lipid accumulation in the liver by modulating AMPK and SREBP-1?"
            ]
        },
        {
            "id": "task847-d16e541a021d4353a917a13c33b05666",
            "input": "Most patients are admitted to the hospital through the emergency department (ED), and ED waiting times partly reflect the availability of inpatient beds. We test whether the balance between daily hospital admissions and discharges affects next-day ED length of stay.', 'We conducted a cross-sectional study of hospitals in metropolitan Toronto, served by a single emergency medical services provider in a publicly funded system. During a 3-year period, we evaluated the daily ratio of admissions to discharges at each hospital and the next-day median ED length of stay in the same hospital by using linear regression.', 'Across hospitals, the daily mean (SD) 50th percentile ED length of stay averaged 218 (51) minutes. As the inpatient admission-discharge ratio increased or decreased, next-day ED length of stay changed accordingly. Compared with ratios of 1.0, those less than 0.6 were associated with an 11-minute (95% confidence interval [CI] 5 to 16 minutes) shorter next-day median ED length of stay; at admission-discharge ratios of 1.3 to 1.4, ED length of stay was significantly prolonged by 5 minutes (95% CI 3 to 6 minutes). Admission-discharge ratios on weekends and among medical inpatients had a stronger influence on next-day ED length of stay; effects were also greater among higher-acuity and admitted ED patients.",
            "output": [
                "Does disequilibrium between admitted and discharged hospitalized patients affect emergency department length of stay?"
            ]
        },
        {
            "id": "task847-094c1a35b5014694a839f317c6366abf",
            "input": "Gender has been shown to affect endothelial function of the forearm circulation in patients with type 2 diabetes, but data on the renal circulation are lacking. We hypothesized that renal vascular nitric oxide (NO) availability is higher, and oxidative stress lower, in female compared to male patients with type 2 diabetes.', 'In 41 male and 39 female patients with type 2 diabetes, renal plasma flow (RPF) was determined by constant infusion input clearance at baseline and following infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 4.25 mg/kg) to assess basal renal vascular NO availability. After a subsequent infusion of L-arginine (100 mg/kg) to restore baseline conditions, vitamin C (45 mg/kg) was co-infused to determine levels of oxidative stress in the renal circulation.', 'Baseline renal haemodynamics were similar between genders. L-NMMA-induced renal vasoconstriction was more pronounced in females compared to males (-89 +/- 69 versus -60 +/- 52 ml/min/1.73 m(2), P = 0.03). After administration of L-arginine to restore baseline perfusion, the co-infusion of vitamin C led to a lesser increase of RPF in females than in males (+37 +/- 86 versus +60 +/- 52 ml/min/1.73 m(2), P = 0.05).",
            "output": [
                "Is gender related to alterations of renal endothelial function in type 2 diabetes?"
            ]
        },
        {
            "id": "task847-42d78a6cf93e41c9900785a53bf87ec3",
            "input": "B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP) are important diagnostic tools for patients with suspected cardiac disorders. The aim of this study was to evaluate the predictive value of plasma NT-pro-BNP in identifying cardiac metastases in patients with non-small cell lung cancer (NSCLC) and dyspnoea.', 'A total of 120 patients, median age 62 years (range 46-83), with NSCLC and dyspnoea were studied. Patients with heart failure or documented coronary artery disease were excluded. Echocardiographic imaging was used to detect cardiac metastases and estimate global left ventricular function. Ejection fraction and E/A ratio from transmitral inflow pattern were calculated. Plasma NT-pro-BNP was also measured. 72 patients (72/120, 60%) with cardiac metastases were identified.', 'NT-pro-BNP was significantly higher in patients with metastases (1347.5 +/- 1004.30 pg/ml vs. 159.02 +/- 93.29 pg/ml; p = 0.001). No differences between groups, regarding s-creatinine (p = 0.45), haemoglobin (p = 0.71), left ventricular hypertrophy (p = 0.91), and diastolic dysfunction (p = 0.79), were observed.",
            "output": [
                "Is pro-brain natriuretic peptide a sensitive marker for detecting cardiac metastases in patients with non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-3dc0b2e77d99456396f893d41ff4307e",
            "input": "To investigate whether angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) are implicated in the hypoxemic resuscitation from hemorrhagic shock.', 'Twenty rabbits were subjected to hemorrhagic shock after blood exsanguination; resuscitation was performed by infusion of the shed blood in ten rabbits under normoxemic conditions (NormoxRes) and in 10 under hypoxemic conditions (HypoxRes); four rabbits were subjected to sham operation. Serum was drawn at serial time intervals; serum was applied for stimulation of U937 monocytes.', 'Serum concentrations of Ang2 were higher in the NormoxRes group compared to the HypoxRes group at 90 min (p: 0.049) and at 120 min (p: 0.028). Serum concentrations of VEGF did not differ between groups. Concentrations of VEGF in the supernatants of U937 stimulated with sera of all groups were below detection limit. The wet to dry lung ratio of the HypoxRes group was significantly lower than the NormoxRes group (p<0.0001).",
            "output": [
                "Is hypoxemic resuscitation after hemorrhagic shock accompanied by reduced serum levels of angiopoietin-2?"
            ]
        },
        {
            "id": "task847-b0b3e9e5b9e84fe093447334919ad0d0",
            "input": "This study was aimed to evaluate the analgesic efficacy duration of analgesia, and side effects of two different doses of caudal neostigmine used with levobupivacaine in children.', \"Sixty boys, between 5 months and 5 years, undergoing genitourinary surgery were allocated randomly to one of three groups (n =20 each). Group I patients received caudal 0.25% levobupivacaine (1 ml.kg(-1)) alone. Groups II and III patients received neostigmine (2 and 4 microg.kg(-1) respectively) together with levobupivacaine used in the same does as Group I. Pain scores were assessed using Children's and Infant's Postoperative Pain Scale (CHIPPS) at 15th (t(1)) min after arrival to postanesthetic care unit, and 1st (t(2)), 2nd (t(3)), 3rd (t(4)), 4th (t(5)), 8th (t(6)), 16th (t(7)), and 24th (t(8)) hour postoperatively. Duration of analgesia, amount of additional analgesic (paracetamol), score of motor blockade and complications were recorded for 24 h postoperatively, and compared between groups.\", 'CHIPPS scores were higher during t(2), t(3), t(6), t(7), and t(8) periods, duration of analgesia was shorter, and total analgesic consumption was higher in Group I compare to neostigmine groups (P < 0.05). Duration of postoperative analgesia and total analgesic consumption were similar in Groups II and III (P > 0.05). Adverse effects were not different between three groups.",
            "output": [
                "Does two different doses of caudal neostigmine co-administered with levobupivacaine produce analgesia in children?"
            ]
        },
        {
            "id": "task847-236f8df315db4b52b27b4b8ee968626f",
            "input": "Malignant melanoma risk factors have been studied in different geographical area populations. However, no study has focused on risk factors which are more frequently associated to the over 60's age group.\", 'A case-control study was performed that included 160 patients age > or = 60 years diagnosed of cutaneous melanoma and 318 controls matched for age and sex. Both groups were assessed, by personal interview and physical examination, for different phenotype characteristics (hair and eye color, phototype), the presence of other cutaneous lesions (solar lentigines, actinic keratoses and nevi), degree and type of solar exposure and personal and family past history of cutaneous or non-cutaneous cancer. Differences were evaluated by contingency tables and univariate and multivariate logistic regression.', 'Of 17 factors, those risk factors with a strong effect on the development of melanoma in the elderly were: fair eyes, severe sunburns, years of occupational sun exposure, smoking, > 50 melanocytic nevi and personal history of NMSC and other non-cutaneous neoplasias.",
            "output": [
                "Are smoking , sun exposure , number of nevi and previous neoplasias risk factors for melanoma in older patients ( 60 years and over )?"
            ]
        },
        {
            "id": "task847-b274ffc4b2e640d497938bf81b46373a",
            "input": "From 1984 to 2006, studies of sleep in patients with interstitial lung disease revealed disturbed sleep, frequent nocturnal desaturations, nocturnal cough, and obstructive sleep apnea (OSA). Our goal was to analyze OSA in an outpatient population of stable patients with idiopathic pulmonary fibrosis (IPF).', 'Patients with IPF who had been followed up in the Vanderbilt Pulmonary Clinic were asked to participate. All patients were given a diagnosis of IPF by the 2000 American Thoracic Society consensus statement criteria. Subjects completed an Epworth sleepiness scale (ESS) questionnaire and a sleep apnea scale of sleep disorders questionnaire (SA-SDQ) before undergoing nocturnal polysomnography (NPSG). OSA was defined as an apnea-hypopnea index (AHI) of > 5 events per hour.', 'Fifty subjects enrolled and completed a NPSG. The mean age was 64.9 years, and the mean BMI was 32.3. OSA was diagnosed in 88% of subjects. Ten subjects (20%) had mild OSA (AHI, 5 to 15 events per hour), and 34 subjects (68%) had moderate-to-severe OSA (AHI, > 15 events per hour). Only 6 subjects (12%) had a normal AHI. One patient was asymptomatic as determined by ESS and SA-SDQ, but had an AHI of 24 events per hour. The sensitivity of the ESS was 75% with a specificity of 15%, whereas the SA-SDQ had a sensitivity of 88% with a specificity of 50%. BMI did not correlate strongly with AHI (r = 0.30; p = 0.05).",
            "output": [
                "Is obstructive sleep apnea common in idiopathic pulmonary fibrosis?"
            ]
        },
        {
            "id": "task847-5fd8d6ae3a4140589502ac27adccf8f2",
            "input": "Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable developmental disorder resulting from complex gene-gene and gene-environment interactions. The most widely used animal model, the spontaneously hypertensive rat (SHR), displays the major symptoms of ADHD (deficits in attention, impulsivity and hyperactivity) and has a disturbance in the noradrenergic system when compared to control Wistar-Kyoto rats (WKY). The aim of the present study was to determine whether the ADHD-like characteristics of SHR were purely genetically determined or dependent on the gene-environment interaction provided by the SHR dam.', 'SHR/NCrl (Charles River, USA), WKY/NCrl (Charles River, USA) and Sprague Dawley rats (SD/Hsd, Harlan, UK) were bred at the University of Cape Town. Rat pups were cross-fostered on postnatal day 2 (PND 2). Control rats remained with their birth mothers to serve as a reference for their particular strain phenotype. Behavior in the open-field and the elevated-plus maze was assessed between PND 29 and 33. Two days later, rats were decapitated and glutamate-stimulated release of [3H]norepinephrine was determined in prefrontal cortex and hippocampal slices.', 'There was no significant effect of \"strain of dam\" but there was a significant effect of \"pup strain\" on all parameters investigated. SHR pups travelled a greater distance in the open field, spent a longer period of time in the inner zone and entered the inner zone of the open-field more frequently than SD or WKY. SD were more active than WKY in the open-field. WKY took longer to enter the inner zone than SHR or SD. In the elevated-plus maze, SHR spent less time in the closed arms, more time in the open arms and entered the open arms more frequently than SD or WKY. There was no difference between WKY and SD behavior in the elevated-plus maze. SHR released significantly more [3H]norepinephrine in response to glutamate than SD or WKY in both hippocampus and prefrontal cortex while SD prefrontal cortex released more [3H]norepinephrine than WKY. SHR were resilient, cross-fostering did not reduce their ADHD-like behavior or change their neurochemistry. Cross-fostering of SD pups onto SHR or WKY dams increased their exploratory behavior without altering their anxiety-like behavior.",
            "output": [
                "Does cross-fostering alter the neurochemistry or behavior of spontaneously hypertensive rats?"
            ]
        },
        {
            "id": "task847-88ad0cec520b4b9380b03a48242d59c9",
            "input": "Cigarette smoking is a risk factor for diffuse parenchymal lung disease. Risk factors for subclinical parenchymal lung disease have not been described.', 'To determine if cigarette smoking is associated with subclinical parenchymal lung disease, as measured by spirometric restriction and regions of high attenuation on computed tomography (CT) imaging.', 'We examined 2,563 adults without airflow obstruction or clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, a population-based cohort sampled from six communities in the United States. Cumulative and current cigarette smoking were assessed by pack-years and urine cotinine, respectively. Spirometric restriction was defined as a forced vital capacity less than the lower limit of normal. High attenuation areas on the lung fields of cardiac CT scans were defined as regions having an attenuation between -600 and -250 Hounsfield units, reflecting ground-glass and reticular abnormalities. Generalized additive models were used to adjust for age, gender, race/ethnicity, smoking status, anthropometrics, center, and CT scan parameters.', 'The prevalence of spirometric restriction was 10.0% (95% confidence interval [CI], 8.9-11.2%) and increased relatively by 8% (95% CI, 3-12%) for each 10 cigarette pack-years in multivariate analysis. The median volume of high attenuation areas was 119 cm(3) (interquartile range, 100-143 cm(3)). The volume of high attenuation areas increased by 1.6 cm(3) (95% CI, 0.9-2.4 cm(3)) for each 10 cigarette pack-years in multivariate analysis.",
            "output": [
                "Is cigarette smoking associated with subclinical parenchymal lung disease : the Multi-Ethnic Study of Atherosclerosis ( MESA ) -lung study?"
            ]
        },
        {
            "id": "task847-0e78c6e915bd4562a31ee7456df7c1be",
            "input": "The intertidal copepod Tigriopus californicus is a model for studying the process of genetic divergence in allopatry and for probing the nature of genetic changes that lead to reproductive isolation. Although previous studies have revealed a pattern of remarkably high levels of genetic divergence between the populations of this species at several spatial scales, it is not clear what types of historical processes are responsible. Particularly lacking are data that can yield insights into population history from the finest scales of geographic resolution.', 'Sequence variation in both cytochrome b (CYTB, mtDNA) and the rieske iron-sulfur protein (RISP, nuclear) are examined at a fine scale within four different regions for populations of T. californicus. High levels of genetic divergence are seen for both genes at the broader scale, and genetic subdivision is apparent at nearly all scales in these populations for these two genes. Patterns of polymorphism and divergence in both CYTB and RISP suggest that selection may be leading to non-neutral evolution of these genes in several cases but a pervasive pattern of neither selection nor coadaptation is seen for these markers.",
            "output": [
                "Do investigations of fine-scale phylogeography in Tigriopus californicus reveal historical patterns of population divergence?"
            ]
        },
        {
            "id": "task847-f1ee5e09a98b4b4d830f80d1a37f2497",
            "input": "Ptosis and strabismus are 2 common presenting complaints of preschool-age patients. In both cases, these conditions can be benign and require no further workup. However, sudden onset of these findings can indicate a more serious neurologic problem. If a patient presents with multiple neurologic signs, a sudden onset eye turn, or ptosis, the patient must undergo a workup to rule out a pathologic etiology, specifically a brain tumor. The workup should include neuroimaging. If the results of the neuroimaging are normal, and the findings are variable, myasthenia gravis should be considered, and additional testing should be ordered to assist in the diagnosis.', 'This case report presents a 3-year-old boy who presented with a sudden onset of ptosis and hypertropia. Diagnosis of myasthenia gravis was made based on clinical presentation and response to ice pack testing. The patient was treated with pyridostigmine (Mestinon; Valent Pharmaceuticals, Costa Mesa, California) and has shown improvement in his clinical signs.",
            "output": [
                "Do ptosis and cranial nerve IV palsy reveal juvenile myasthenia gravis?"
            ]
        },
        {
            "id": "task847-6b0a62e9ce9e456b919e173e63b96289",
            "input": "Transcription factor HaDREB2 was identified in sunflower (Helianthus annuus L.) as a drought-responsive element-binding factor 2 (DREB2) with unique properties. HaDREB2 and the sunflower Heat Shock Factor A9 (HaHSFA9) co-activated the Hahsp17.6G1 promoter in sunflower embryos. Both factors could be involved in transcriptional co-activation of additional small heat stress protein (sHSP) promoters, and thus contribute to the HaHSFA9-mediated enhancement of longevity and basal thermotolerance of seeds.', 'We found that overexpression of HaDREB2 in seeds did not enhance longevity. This was deduced from assays of basal thermotolerance and controlled seed-deterioration, which were performed with transgenic tobacco. Furthermore, the constitutive overexpression of HaDREB2 did not increase thermotolerance in seedlings or result in the accumulation of HSPs at normal growth temperatures. In contrast, when HaDREB2 and HaHSFA9 were conjointly overexpressed in seeds, we observed positive effects on seed longevity, beyond those observed with overexpression of HaHSFA9 alone. Such additional effects are accompanied by a subtle enhancement of the accumulation of subsets of sHSPs belonging to the CI and CII cytosolic classes.",
            "output": [
                "Does the HaDREB2 transcription factor enhance basal thermotolerance and longevity of seeds through functional interaction with HaHSFA9?"
            ]
        },
        {
            "id": "task847-bba0123c74374ec78b923e953f71ae37",
            "input": "Repeated hypoglycemia is associated with hypoglycemia-associated autonomic failure (HAAF), a syndrome of defective counterregulation.', 'HAAF increases the risk of severe hypoglycemia in diabetes, although its mechanism remains unresolved. Because beta-endorphin influences the autonomic response to hypoglycemia via opioid receptor activation, we hypothesized that it is also involved in the pathogenesis of HAAF.', 'We asked whether opioid receptor blockade during antecedent hypoglycemia (60 mg/dl) on d 1 would prevent development of HAAF on d 2 in eight nondiabetic subjects (five males, 3 females; age, 28 +/- 3.5 yr; body mass index, 24.2 +/- 2.1 kg/m(2)). On four occasions, d 1 was: 1) two 90-min hypoglycemic clamps (N-); 2) two 90-min hypoglycemic clamps plus naloxone (N+); 3) two euglycemic 90-min clamps (C); or 4) two euglycemic 90-min clamps plus naloxone (C+).', 'Day 1 hypoglycemia caused marked deterioration of d 2 hormonal responses to hypoglycemia, consistent with HAAF-i.e. decreased plasma epinephrine, norepinephrine, and glucagon compared to control (C) (374 +/- 71 vs. 810 +/- 94, 307 +/- 65 vs. 686 +/- 98, and 71 +/- 9 vs. 93 +/- 4 pg/ml, respectively, P < 0.01), as well as in endogenous glucose production (24 vs. 163%; P < 0.01). In contrast, naloxone on d 1 completely prevented the defective counterregulatory responses; epinephrine, norepinephrine, and glucagon (852 +/- 82, 769 +/- 77, and 98 +/- 7 pg/ml) and endogenous glucose production recovery (167%) were identical to those after d 1 euglycemia (P < NS for all). Infusion of naloxone alone during euglycemia on d 1 (C+) had no effect on d 2 responses.",
            "output": [
                "Is hypoglycemia-associated autonomic failure prevented by opioid receptor blockade?"
            ]
        },
        {
            "id": "task847-6144075353b14c9a870c7130c5bcf250",
            "input": "The purpose of this study was to evaluate the effect of various local anesthetics on chondrocyte viability in articular cartilage by use of a bovine disk model.', 'Full-thickness bovine cartilage disks were isolated from the condylar surfaces of the radial-carpal joint by use of a 4-mm biopsy punch and were incubated in various concentrations of local anesthetics (e.g., bupivacaine) for varying amounts of time and stained for membrane integrity by use of ethidium bromide and SYTO 13 stain (Molecular Probes, Carlsbad, CA). Cell and nuclear morphology was assessed by transmission electron microscopy.', 'The addition of local anesthetics (i.e., 0.25% bupivacaine, 1% lidocaine, and 0.5% ropivacaine) to bovine articular cartilage disks had a negative effect on chondrocyte viability. Culturing bovine articular cartilage disks for increasing periods of time decreased chondrocyte viability for each of the local anesthetics, with significant negative correlations being shown between time of exposure to the drug and chondrocyte viability. These effects were also affected by the presence or absence of epinephrine in local anesthetic preparations.",
            "output": [
                "Do local anesthetics induce chondrocyte death in bovine articular cartilage disks in a dose- and duration-dependent manner?"
            ]
        },
        {
            "id": "task847-58110010717e42dba5e21684ee64b623",
            "input": "A randomised, prospective clinical trial with parallel groups was carried out in a single centre.', 'The experimental (gel) group (n=41) applied a bioadhesive 0.2% chlorhexidine gel to the wound during the first postoperative week and a control (rinse) group (n=32) used a 0.12% (v/v) chlorhexidine mouthrinse during the first week following third molar extraction. Patients were evaluated on the third and seventh postoperative day.', \"Alveolar osteitis was evaluated according to Blum's criteria..\", 'A 70% decrease in postoperative alveolar osteitis in the gel group (P 0.04) was observed. The rinse group had 25% incidence of postoperative alveolar osteitis, whereas the gel group had 7.5%. T equates to a number needed to treat of six (95% confidence interval, 3-144).",
            "output": [
                "Does chlorhexidine gel reduce incidence of alveolar osteitis after extraction of the mandibular third molars?"
            ]
        },
        {
            "id": "task847-1c750a30d37f495398698acae8dc5ab9",
            "input": "Cytomegalovirus (CMV) remains the most common viral infection after pancreas-kidney transplantation (PKT). Comparative studies about CMV prophylaxis in PKT have not been developed.', 'We analyzed CMV disease in a cohort of 84 PKT recipients. All received intravenous ganciclovir during treatment with anti-thymocyte globulin and later one of the following options for pre-transplant CMV-seropositive recipients: (a) no prophylaxis (n=10 patients), (b) preemptive therapy (PT) (n=13), or (c) continuous prophylaxis (CP) for 12 weeks (n=29). Pre-transplant CMV-seronegative recipients received CP (n=21).', 'Eleven patients were excluded because of organ explantation in the first 15 days. Incidence of CMV disease in seropositive recipients was 30% under no prophylaxis, 23% under PT, and 6.9% under CP. Incidence of CMV disease under CP was 33.3% in seronegative recipients. Six of 9 episodes of CMV disease under CP occurred after finishing prophylaxis. Under CP, the incidence of CMV disease was significantly higher in seronegative than in seropositive recipients (P<0.05).",
            "output": [
                "Is preemptive therapy adequate for prevention of cytomegalovirus disease in pancreas-kidney transplant recipients?"
            ]
        },
        {
            "id": "task847-4a42fde9f3e9487d8e5f5d7c210ce077",
            "input": "Complement protein C4d has been used as a marker of antibody mediated rejection in kidney allografts. C4d has been shown to be deposited also in chronic kidney allograft rejection, and frequently in acute liver allograft rejection. In chronic liver allograft rejection there is limited data of C4d positivity.', '7 liver allografts explanted at retransplantation due to chronic rejection were examined for expression of C4d. Immunoperoxidase technique on frozen sections was used. The \"zero\" biopsies of the same livers at the first transplantation served as controls.', 'Expression of C4d was significantly increased in portal and central veins as well as in the portal stroma of the grafts with chronic rejection when compared to the expression at implantation of the graft.",
            "output": [
                "Is vascular deposition of complement C4d increased in liver allografts with chronic rejection?"
            ]
        },
        {
            "id": "task847-9c1fe8d0f2b64f21bb3a18fd33cc65f7",
            "input": "To fully understand the cytotoxicity of after-degradation QDs, we synthesized CdS QDs and investigated its toxicity mechanism.', 'Biomimetic method was proposed to synthesize cadmium sulfide (CdS) QDs. Thereafter MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay was conducted to evaluate their cytotoxicity. To investigate the toxicity mechanism, we subsequently conducted intracellular reactive oxygen species (ROS) measurement with DCFH-DA, glutathione (GSH) measurement with DTNB, and cellular cadmium assay using atomic absorption spectrometer. Microsized CdS were simultaneously tested as a comparison.', \"MTT assay results indicated that CdS QDs are more toxic than microsized CdS especially at concentrations below 40 microg/ml. While microsized CdS did not trigger ROS elevation, CdS QDs increase ROS by 20-30% over control levels. However, they both deplete cellular GSH significantly at the medium concentration of 20 microg/ml. In the presence of NAC, cells are partially protected from CdS QDs, but not from microsized particles. Additionally, nearly 20% of cadmium was released from CdS nanoparticles within 24h, which also accounts for QDs' toxicity.",
            "output": [
                "Do intracellular oxidative stress and cadmium ions release induce cytotoxicity of unmodified cadmium sulfide quantum dots?"
            ]
        },
        {
            "id": "task847-04c92e0ab09a4369935b299d9c91dc76",
            "input": "Clinical use of doxorubicin is greatly limited by its severe cardiotoxic side effects. L-carnitine is a vitamin-like substance which has been successfully used in many cardiomyopathies, however, the intracellular mechanism(s) remain unclear. The objective of this study was set to evaluate the protective effect of L-carnitine on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s).', \"Primary cultured neonatal rat cardiomyocytes were treated with doxorubicin (1 \u00b5M) with or without pretreatment with L-carnitine (1-30 mM). Lactate dehydrogenase assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and flow cytometry measurement were used to assess cytotoxicity and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and chemiluminescence assay of superoxide production were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the quantity of cleaved caspase-3, cytosol cytochrome c, and Bcl-x(L) expression.\", \"L-carnitine inhibited doxorubicin-induced reactive oxygen species generation and NADPH oxidase activation, reduced the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased Bcl-x(L) expression, resulting in protecting cardiomyocytes from doxorubicin-induced apoptosis. In addition, L-carnitine was found to increase the prostacyclin (PGI(2)) generation in cardiomyocytes. The siRNA transfection for PGI(2) synthase significantly reduced L-carnitine-induced PGI(2) and L-carnitine's protective effect. Furthermore, blockade the potential PGI(2) receptors, including PGI(2) receptors (IP receptors), and peroxisome proliferator-activated receptors alpha and delta (PPAR\u03b1 and PPAR\u03b4), revealed that the siRNA-mediated blockage of PPAR\u03b1 considerably reduced the anti-apoptotic effect of L-carnitine.",
            "output": [
                "Does l-carnitine reduce doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes?"
            ]
        },
        {
            "id": "task847-b732f44cbf954e4a9146669a2af93d81",
            "input": "Stat6 signaling is active in cancer cells and IL-4-induced Stat6 activities or Stat6 activational phenotypes vary among cancer cells. This study aimed at investigating possible mechanism(s) involved in the formation of varying Stat6 activities/phenotypes.', \"Stat6 regulatory genes, SOCS-1 and SHP-1, were examined for mRNA expression using RT-PCR, and their promoter DNA methylation was assayed by methylation-specific PCR in Stat6-phenotyped colon cancer cell lines. DNA methylation was then verified by sequencing. RT-PCR assay and Western blotting were used to detect the expression of SOCS-1 and SHP-1 after demethylation using 5-aza-2'-deoxycytidine.\", \"Compared with Stat6(null) Caco-2 cells, Stat6(high) HT-29 cells showed decreased constitutive expression of SOCS-1 and SHP-1, which correlated with DNA hypermethylation in these genes' promoters. Interestingly, demethylation in HT-29 cells recovered the constitutive expression of SOCS-1 and SHP-1.",
            "output": [
                "Does dNA methylation regulate constitutive expression of Stat6 regulatory genes SOCS-1 and SHP-1 in colon cancer cells?"
            ]
        },
        {
            "id": "task847-42738a1e2db844589796bc33dfe3de4c",
            "input": "Previous studies have reported that smoking abstinence rates are increased when nicotine skin patch treatment is initiated prior to the target quit smoking date, as compared with conventional treatment beginning on the quit date. We hypothesized that smoking in the presence of continuous levels of nicotine would attenuate the reinforcing effects of cigarette smoking and lead to a decline in dependence on inhaled nicotine, thus facilitating cessation.', 'This study involved four groups of smokers (n = 100 per group) who received either nicotine patch (21 mg/24 hr) or placebo patch treatment for 2 weeks before the quit smoking date, and during this period, smoked their usual brands of cigarettes or switched to low-tar and nicotine cigarettes: a 2 (nicotine patch) x 2 (cigarette type) factorial design. From the quit date on, all groups received standard nicotine patch treatment, consisting of 6 weeks of 21 mg/24 hr, 2 weeks of 14 mg/24 hr, and 2 weeks of 7 mg/24 hr. Abstinence was defined as self-report of no smoking from the quit date on, confirmed by expired-air carbon monoxide.', 'Continuous abstinence rates were approximately doubled by precessation nicotine patch treatment. The treatment mainly benefited smokers with lower levels of dependence, based on Fagerstr\u00f6m Test for Nicotine Dependence score. All treatments were well tolerated.",
            "output": [
                "Does precessation treatment with nicotine patch significantly increase abstinence rates relative to conventional treatment?"
            ]
        },
        {
            "id": "task847-56a7b176759b406b80a058e7874d5ac3",
            "input": "To investigate the effect of osteopontin (OPN) on the invasion and metastasis of human hapatocellular carcinoma (HCC).', 'HCC cell lines (HCC-LM3) were transfected with the chemically synthesized small interfering RNA (siRNA). Real-time PCR and Western blot were used to quantify the mRNA and OPN protein levels. The malignant phenotypes including cellular growth, colony formation and invasion capability of the HCC cells were analyzed.', 'The OPN mRNA and proteins levels were decreased by 75% and 80% in OPN siRNA treated cells. Colony formation and migratory capability were reduced in OPN siRNA treated cells (P < 0.05).",
            "output": [
                "Does [ Interference of osteopontin expression inhibit the invasion and metastasis of human hepatocellular carcinoma cell lines ]?"
            ]
        },
        {
            "id": "task847-36af0ded8e9f48cb9d363bcd9d23b7e2",
            "input": "To test the hypothesis that diffuse abnormalities precede axonal damage and atrophy in the MRI normal-appearing tissue of relapsing-remitting (RR) multiple sclerosis (MS) patients, and that these processes continue during clinical remission.', 'Twenty-one recently diagnosed mildly disabled (mean disease duration 2.3 years, mean Expanded Disability Status Scale score of 1.4) RR MS patients and 15 healthy matched controls were scanned with MRI and proton MR spectroscopic imaging ((1)H-MRSI) at 3 T. Metabolite concentrations: N-acetylaspartate (NAA) for neuronal integrity; choline (Cho) for membrane turnover rate; creatine (Cr) and myo-inositol (mI) for glial status were obtained in a 360 cm(3) volume of interest (VOI) with 3D multivoxel (1)H-MRSI. They were converted into absolute amounts using phantom replacement and normalised into absolute concentrations by dividing by the VOI tissue volume fraction obtained from MRI segmentation.', \"The patients' mean VOI tissue volume fraction, 0.92 and NAA concentration, 9.6 mM, were not different from controls' 0.94 and 9.6 mM. In contrast, the patients' mean Cr, Cho and mI levels 7.7, 1.9 and 4.1 mM were 9%, 14% and 20%, higher than the controls' 7.1, 1.6 and 3.4 mM (p = 0.0097, 0.003 and 0.0023).",
            "output": [
                "Does mR spectroscopy indicate diffuse multiple sclerosis activity during remission?"
            ]
        },
        {
            "id": "task847-caf9100ffc604807808c773498219b23",
            "input": "The increased severity of disease associated with the NAP1 strain of Clostridium difficile has been attributed to mutations to the tcdC gene which codes for a negative regulator of toxin production. To assess the role of hyper-production of Toxins A and B in clinical isolates of Clostridium difficile, two NAP1-related and five NAP1 non-related strains were compared.', 'Sequencing was performed on tcdC, tcdR, and tcdE to determine if there were differences that might account for hyper-production of Toxin A and Toxin B in NAP1-related strains. Biological activity of Toxin B was evaluated using the HFF cell CPE assay and Toxin A biological activity was assessed using the Caco-2 Trans-membrane resistance assay.', 'Our results confirm that Toxin A and Toxin B production in NAP1-related strains and ATCC 43255 occurs earlier in the exponential growth phase compared to most NAP1-nonrelated clinical isolates. Despite the hyper-production observed in ATCC 43255 it had no mutations in tcdC, tcdR or tcdE. Analysis of the other clinical isolates indicated that the kinetics and ultimate final concentration of Toxin A and B did not correlate with the presence or lack of alterations in tcdC, tcdR or tcdE.",
            "output": [
                "Does truncation in the tcdC region of the Clostridium difficile PathLoc of clinical isolates predict increased biological activity of Toxin B or Toxin A?"
            ]
        },
        {
            "id": "task847-27f9cd91d51d475f8ac84d32b2cd7e82",
            "input": "The authors investigated the additive prognostic value of the 6-minute walk test (6MWT) to Euroscore in patients with severe aortic stenosis undergoing aortic valve replacement (AVR) METHODS AND RESULTS: 208 patients with severe AS underwent the 6MWT before AVR, as part of a randomised trial (ASSERT) comparing stented and stentless aortic valves. Clinical follow-up was available for 200 patients up to 12 months. The rate of death, myocardial infarction (MI) or stroke (time to first event) was 13% (n = 14) in patients walking <300 metres compared to 4% (n = 4) in those who walked > or =300 metres (p = 0.017). When rate of death, MI or stroke by Euroscore risk was stratified by 6-minute walking distance, the 6MWT added prognostic information. In a Cox regression analysis 6MWT distance was the only variable retained as an independent predictor of the composite outcome of death, MI or stroke at 12 months (HR 0.28 95% CI 0.09 to 0.85, p = 0.025).",
            "output": [
                "Does preoperative 6-minute walk test add prognostic information to Euroscore in patients undergoing aortic valve replacement?"
            ]
        },
        {
            "id": "task847-4130c66934e84c2188215e13b7dbd534",
            "input": "To investigate the effect of high glucose on insulin-induced vascular endothelial growth factor (VEGF) expression in bovine retinal microvascular endothelial cells (BRECs) and to probe into related mechanisms.', 'BRECs were isolated as primary cultures and identified by immunostaining. Passage cells were initially exposed to normal (5 mM) or high glucose (30 mM) for 3 days, and equimolar L-glucose was supplemented for osmotic equation. BRECs were then treated with 100 nM insulin for 24 h or not, and cells were prepared for the determination of VEGF mRNA expression by real-time PCR. VEGF protein was determined by human umbilical vein endothelial cell proliferation assay, immunofluorescence, and ELISA. BRECs were treated with 5 or 30 mM glucose for 3 days and then cells cultured with 5 mM glucose were exposed to the PI3-K inhibitor wortmannin (100 nM), the P42/44 mitogen-activated protein kinase (MAPK) inhibitor U0126 (50 microM), or to the protein kinase C (PKC) inhibitor GF109203X (2 microM) 1 h before addition of 100 nM insulin. Twenty-four hours after incubation with insulin, the cells were subjected to real-time PCR and ELISA analyses.', 'Insulin or high glucose alone markedly increased VEGF mRNA and protein levels in BRECs (P<0.05, two-way ANOVA). However, the combination of insulin and high glucose displayed a weaker effect in promoting VEGF expression than did insulin alone (P<0.05, t-test). Pretreatment of cells with PI3-K inhibitor significantly (P<0.05, one-way ANOVA) suppressed the insulin-induced VEGF expression; neither pretreatment with the PKC inhibitor nor with the P42/p44 MAPK inhibitor showed an effect on the expression of VEGF at the mRNA or protein level (P>0.05, one-way ANOVA).",
            "output": [
                "Does high glucose attenuate insulin-induced VEGF expression in bovine retinal microvascular endothelial cells?"
            ]
        },
        {
            "id": "task847-d53f864d093347329aa7930b7b9d01e5",
            "input": "A retrospective study on patients with chronic nonspecific low back pain (NSLBP).', 'To describe the gait stride characteristics of patients with chronic NSLBP, and to examine the effect of a novel biomechanical device on the gait stride characteristics of these patients.', 'Patient with NSLBP alters their gait patterns. This is considered a protective mechanism as patients try to avoid extensive hip and spine ranges of motion and minimize forces and moments acting on the body. In addition, there are changes in the neuromuscular control system in patients with LBP that could possibly be attributed to the effects of pain on motor control.', 'Nineteen patients underwent a gait test, using an electronic walkway, at baseline and after 12 weeks of treatment. Spatiotemporal parameters were used to identify changes in gait pattern. A novel biomechanical device comprised of 4 modular elements attached to foot-worn platforms was used in the study. The modules are 2 convex shaped biomechanical elements attached to each foot, one is located under the hindfoot region and the other is located under the forefoot region. The device was individually calibrated to each patient. The patients were instructed to walk with the calibrated biomechanical device on a daily basis for a period of 12 weeks.', 'Significant differences were found at baseline and after 12 weeks in normalized velocity (P = 0.03), cadence (P < 0.01), left normalized step length (P = 0.02), right normalized step length (P = 0.02), right swing (P < 0.01), right stance (P < 0.01), left single limb support (P = 0.01), left double limb support (P = 0.02), and right double limb support (P = 0.02).",
            "output": [
                "Does a novel biomechanical device improve gait pattern in patient with chronic nonspecific low back pain?"
            ]
        },
        {
            "id": "task847-64e34f0c53e94fe4a1953a8f5c01d7a7",
            "input": "Human Hsp60 is expressed in the joints of patients with rheumatoid arthritis (RA) and can elicit a regulatory T cell response in the peripheral blood and synovial fluid. However, Hsp60 can also trigger strong proinflammatory pathways. Thus, to understand the nature of these Hsp60-directed responses in RA, it is necessary to study such responses at the molecular, epitope-specific level. This study was undertaken to characterize the disease specificity and function of pan-DR-binding Hsp60-derived epitopes as possible modulators of autoimmune inflammation in RA.', 'Lymphocyte proliferation assays (using (3)H-thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester [CFSE] staining) and measurement of cytokine production (using multiplex immunoassay and intracellular staining) were performed after in vitro activation of peripheral blood mononuclear cells from patients with RA, compared with healthy controls.', 'A disease (RA)-specific immune recognition, characterized by T cell proliferation as well as increased production of tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and IL-10, was found for 3 of the 8 selected peptides in patients with RA as compared with healthy controls (P < 0.05). Intracellular cytokine staining and CFSE labeling showed that CD4+ T cells were the subset primarily responsible for both the T cell proliferation and the cytokine production in RA. Interestingly, the human peptides had a remarkably different phenotype, with a 5-10-fold higher IL-10:TNFalpha ratio, compared with that of the microbial peptides.",
            "output": [
                "Do pan-DR-binding Hsp60 self epitopes induce an interleukin-10-mediated immune response in rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-9bc062afdbe142929b7e3f79fc4b7480",
            "input": "C-reactive protein (CRP) is a nonspecific marker of inflammation that is increased in the brain and serum of patients with Alzheimer's disease (AD), and has been associated with increased risk of developing dementia. Inflammation increases with age, and the number of people reaching age 90 years and older is growing, making the association between inflammation and dementia increasingly relevant. Using a cross-sectional design, we examined whether high levels of serum CRP are associated with increased odds of prevalent dementia in the oldest-old.\", 'Serum CRP levels of 305 participants (mean age +/- standard deviation, 94.3 +/- 2.9 years) from the 90+ Study, a longitudinal cohort study of people aged 90 years and older, were evaluated with respect to all-cause dementia. Levels of CRP were divided into three categories: undetectable (<0.5 mg/dL), detectable (0.5-0.7 mg/dL), and elevated (> or =0.8 mg/dL). Odds ratios (ORs) were calculated using logistic regression, and were adjusted for covariates.', 'Relative to participants with undetectable CRP levels, participants with detectable or elevated CRP levels had increased odds of all-cause dementia (detectable: OR, 3.0; 95% confidence interval, 1.2-7.3; elevated: OR, 5.0; 95% confidence interval, 1.9-12.9). When participants were subdivided by gender, significantly increased ORs were seen only in women.",
            "output": [
                "Are elevated C-reactive protein levels associated with prevalent dementia in the oldest-old?"
            ]
        },
        {
            "id": "task847-cea97e489a574a63a6aac25068ed144d",
            "input": "Mesenchymal stem cells (MSCs) under favorable conditions secrete a spectrum of cytokines that promote the survival of surrounding cells via paracrine mechanisms. We explored the impact of rat pancreatic extract (RPE) on cytokine secretion by MSCs and examined the influence of administration of conditioned media of MSCs treated with RPE on blood glucose levels in diabetic rats.', 'Cytokine levels (IGF-1, VEGF, bFGF) in conditioned media of MSCs treated with RPE were measured using enzyme-linked immunosorbent assays. We estimated blood glucose levels of STZ-induced diabetic rats following intraperitoneal injection of conditioned media from RPE-treated MSCs. We analyzed histopathology of pancreatic islets by insulin immunostaining and apoptosis through a TUNEL assay.', 'Levels of IGF-1, VEGF, and bFGF were significantly increased in RPE-CM compared with control media. Administration of conditioned media of RPE-treated MSCs significantly lowered the blood glucose levels of diabetic rats. After RPE treatment the insulin-positive area was increased and apoptosis of pancreatic beta cells decreased.",
            "output": [
                "Do mesenchymal stem cells treated with rat pancreatic extract secrete cytokines that improve the glycometabolism of diabetic rats?"
            ]
        },
        {
            "id": "task847-2cbbc6ebafe446dab448821ed8ca1f98",
            "input": "Statin disposition and response are greatly determined by the activities of drug metabolizing enzymes and efflux/ uptake transporters. There is little information on the regulation of these proteins in human cells after statin therapy. In this study, the effects of atorvastatin and simvastatin on mRNA expression of efflux (ABCB1, ABCG2 and ABCC2) and uptake (SLCO1B1, SLCO2B1 and SLC22A1) drug transporters in Caco-2 and HepG2 cells were investigated.', 'Quantitative real-time PCR was used to measure mRNA levels after exposure of HepG2 and Caco-2 cells to statins.', 'Differences in mRNA basal levels of the transporters were as follows: ABCC2>ABCG2>ABCB1>SLCO1B1>>>SLC22A1>SLC O2B1 for HepG2 cells, and SLCO2B1>>ABCC2>ABCB1>ABCG2>>>SLC22A1 for Caco-2 cells. While for HepG2 cells, ABCC2, ABCG2 and SLCO2B1 mRNA levels were significantly up-regulated at 1, 10 and 20 micromol/L after 12 or 24 h treatment, in Caco-2 cells, only the efflux transporter ABCB1 was significantly down-regulated by two-fold following a 12 h treatment with atorvastatin. Interestingly, whereas treatment with simvastatin had no effect on mRNA levels of the transporters in HepG2 cells, in Caco-2 cells the statin significantly down-regulated ABCB1, ABCC2, SLC22A1, and SLCO2B1 mRNA levels after 12 or 24 h treatment.",
            "output": [
                "Are the expression of efflux and uptake transporters regulated by statins in Caco-2 and HepG2 cells?"
            ]
        },
        {
            "id": "task847-42a05434bfa8424eb1b972cc10ba1eee",
            "input": "To describe the common locations of active trigger points (TrPs) in the temporalis muscle and their referred pain patterns in chronic tension type headache (CTTH), and to determine if pressure sensitivity maps of this muscle can be used to describe the spatial distribution of active TrPs.', 'Forty women with CTTH were included. An electronic pressure algometer was used to assess pressure pain thresholds (PPT) from 9 points over each temporalis muscle: 3 points in the anterior, medial and posterior part, respectively. Both muscles were examined for the presence of active TrPs over each of the 9 points. The referred pain pattern of each active TrP was assessed.', 'Two-way analysis of variance detected significant differences in mean PPT levels between the measurement points (F=30.3; P<0.001), but not between sides (F=2.1; P=0.2). PPT scores decreased from the posterior to the anterior column (P<0.001). No differences were found in the number of active TrPs (F=0.3; P=0.9) between the dominant side the nondominant side. Significant differences were found in the distribution of the active TrPs (chi2=12.2; P<0.001): active TrPs were mostly found in the anterior column and in the middle of the muscle belly. The analysis of variance did not detect significant differences in the referred pain pattern between active TrPs (F=1.1, P=0.4). The topographical pressure pain sensitivity maps showed the distinct distribution of the TrPs indicated by locations with low PPTs.",
            "output": [
                "Are multiple active myofascial trigger points and pressure pain sensitivity maps in the temporalis muscle related in women with chronic tension type headache?"
            ]
        },
        {
            "id": "task847-326994ec784b466a961cdd310e90a03e",
            "input": "Several studies have reported functional improvement after transplantation of in vivo-derived neural progenitor cells (NPC) into injured spinal cord. However, the potential of human embryonic stem cell-derived NPC (hESC-NPC) as a tool for cell replacement of spinal cord injury (SCI) should be considered.', 'We report on the generation of NPC as neural-like tubes in adherent and feeder-free hESC using a defined media supplemented with growth factors, and their transplantation in collagen scaffolds in adult rats subjected to midline lateral hemisection SCI.', 'hESC-NPC were highly expressed molecular features of NPC such as Nestin, Sox1 and Pax6. Furthermore, these cells exhibited the multipotential characteristic of differentiating into neurons and glials in vitro. Implantation of xenografted hESC-NPC into the spinal cord with collagen scaffold improved the recovery of hindlimb locomotor function and sensory responses in an adult rat model of SCI. Analysis of transplanted cells showed migration toward the spinal cord and both neural and glial differentiation in vivo.",
            "output": [
                "Do human embryonic stem cell-derived neural precursor transplants in collagen scaffolds promote recovery in injured rat spinal cord?"
            ]
        },
        {
            "id": "task847-edc6b45c665a40ce8e85df4ea02b5af1",
            "input": "To quantify the environmental component of aetiology of overweight and obesity by examining the relationship between the degree of overweight in dogs and cats and the degree of overweight in their owners.', 'Cross-sectional study. Main outcome measures of the owners were weight, height (stature) and BMI. Of the animals, weight and divergence from ideal weight were measured by a veterinarian.', 'Three veterinary clinics in Amsterdam, The Netherlands.', 'Dogs and cats, together with their owners, who visited the veterinary clinic. Dogs and cats had to be older than 1 year, and their owners had to be at least 21 years old. After exclusion, there remained forty-seven pairs of dogs and their owners and thirty-six pairs of cats and their owners.', 'We found a significant relationship between the degree of overweight of dogs and the BMI of their owners (r = 0.31). Correction for length of ownership, gender and age of the animal, and gender, age, education level and activity score of the owner did not materially affect this relationship. However, after correction for the amount of time the dog was being walked each day, this relationship disappeared. No significant relationship was found between the degree of overweight of cats and the BMI of their owners.",
            "output": [
                "Is overweight in dogs , but not in cats , related to overweight in their owners?"
            ]
        },
        {
            "id": "task847-1d0308aefcbb4fdd9059676e3236463d",
            "input": "Several studies have shown excess mortality among hip fracture patients compared with the normal population of the same age. Finnish guidelines for medical treatment of hip fracture patients recommend anti-osteoporosis medication and the daily concomitant use of prescribed calcium and vitamin D supplements. However, whether post-fracture use of calcium and vitamin D supplements is associated with survival in such patients has not been evaluated.', \"To study the association between survival in hip fracture patients and patients' sex and age, pre-fracture vitamin D status, American Society of Anesthesiologists - Physical Status (ASA-PS) class, type of fracture and post-fracture use of prescribed calcium plus vitamin D and anti-osteoporotic medication.\", \"The study population was 221 hip fracture patients primarily treated in acute care for a new hip fracture in 2003-4 in two Finnish hospitals. After a median of 27.5 months from the fracture, a questionnaire was sent to all patients who were still alive at the time (n = 137). The patients were queried about their use of prescribed calcium plus vitamin D supplementation and of anti-osteoporotic drugs. The follow-up time for use of anti-osteoporotic medication and prescribed calcium and vitamin D was 19.5-36 months (median 27.5 months). Data on the use of prescribed calcium plus vitamin D supplementation and anti-osteoporotic drugs were checked against information on reimbursement of drug prescriptions held by the Finnish Social Insurance Institution. A total of 4 years' (48 months') survival data for all patients in the study population was also obtained, with the dates of patient deaths being checked against Official National and Regional population statistics. Patient survival was analysed using both the Bayesian multivariate analysis and the life table method.\", 'In the multivariate analysis, the combination of variables that best explained post-fracture survival was as follows: age <80 years; ASA-PS class 1-2 (ASA-PS class 1 and 2 data were combined in calculations); post-fracture use of prescribed calcium plus vitamin D supplements concomitantly with anti-osteoporotic drugs; post-fracture use of prescribed calcium plus vitamin D supplements; post-fracture use of anti-osteoporotic drugs only; and type of fracture (femoral neck or subtrochanteric). This model correctly predicted 74% of cases. At 36 months, we observed a 36% reduction in deaths in females who used prescribed calcium plus vitamin D supplementation and a corresponding 43% reduction in males. Survival of females who used anti-osteoporotic drugs concomitantly was even greater (43% reduction in deaths) over the entire follow-up period. Excess mortality was highest in females and males who used neither anti-osteoporotic drugs nor prescribed calcium and vitamin D.",
            "output": [
                "Is post-fracture prescribed calcium and vitamin D supplements alone or , in females , with concomitant anti-osteoporotic drugs associated with lower mortality in elderly hip fracture patients : a prospective analysis?"
            ]
        },
        {
            "id": "task847-39b26985fb9e46d787f79c0b3a65ceef",
            "input": "Histamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. In humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. We reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (CM) in mice infected with Plasmodium berghei ANKA. Histamine exerts its biological effects through four different receptors designated H1R, H2R, H3R, and H4R.', 'In the present work, we explored the role of histamine signaling via the histamine H3 receptor (H3R) in the pathogenesis of murine CM. We observed that the lack of H3R expression (H3R(-/-) mice) accelerates the onset of CM and this was correlated with enhanced brain pathology and earlier and more pronounced loss of blood brain barrier integrity than in wild type mice. Additionally tele-methylhistamine, the major histamine metabolite in the brain, that was initially present at a higher level in the brain of H3R(-/-) mice was depleted more quickly post-infection in H3R(-/-) mice as compared to wild-type counterparts.",
            "output": [
                "Does histamine H ( 3 ) receptor-mediated signaling protect mice from cerebral malaria?"
            ]
        },
        {
            "id": "task847-521fb24e4a8e4a1aa738661599cc67ed",
            "input": "Previous research in fetuses with increased nuchal translucency (NT) showed abnormal lymphatic endothelial differentiation characteristics, including increased vascular endothelial growth factor (VEGF)-A expression, and aberrant smooth muscle cells (SMCs) surrounding enlarged jugular lymphatic sacs (JLS). We hypothesized that abnormal Sonic hedgehog (Shh) expression would result in altered VEGF-A signaling in the lymphatic endothelial cells of the JLS and that aberrant acquisition of SMCs could be caused by downregulation of forkhead transcription factor FOXC2 and upregulation of platelet-derived growth factor (PDGF)-B in the lymphatic endothelial cells of the JLS.', 'Five trisomy 21 fetuses and four controls were investigated using immunohistochemistry for Shh, VEGF-A, FOXC2 and PDGF-B expression in the lymphatic endothelial cells of the JLS.', 'An increased Shh, VEGF-A and PDGF-B expression, and decreased FOXC2 expression were shown in the lymphatic endothelial cells of the JLS of the trisomic fetuses.",
            "output": [
                "Does abnormal Shh and FOXC2 expression correlate with aberrant lymphatic development in human fetuses with increased nuchal translucency?"
            ]
        },
        {
            "id": "task847-5b9c3bbc338e4e1e9196314ff756fb24",
            "input": "Adherence to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea is poor. Risk factors for nonadherence are not well understood but may reflect individual or neighborhood socioeconomic factors. We sought to determine the association of socioeconomic status and initial CPAP adherence.', 'Retrospective cohort study, 2005 to 2006.', 'Philadelphia VA Medical Center.', 'Of 330 consecutive veterans who met study criteria for initiation of CPAP therapy for newly diagnosed sleep apnea, 266 had complete data for study inclusion.', 'N/A.', 'Through a multivariable logistic regression model, using an outcome of objectively measured CPAP use - 4 h daily during the first week of treatment, we tested whether patients from higher socioeconomic neighborhoods had higher CPAP adherence. We measured neighborhood socioeconomic status with an index derived from the 2000 U.S. Census at the block group-level composed of median household income, male and female employment, adult high school completion, married households, and minority composition.', 'CPAP adherence > 4 h occurred on 48.9% of 1,805 patient-days observed for the 266 subjects. After adjustment for individual sociodemographic characteristics and medical comorbidity, the probability of daily CPAP use 4 h ranged from 34.1% (95% CI, 26.4-42.7) for subjects from a low socioeconomic neighborhood (5th percentile) to 62.3% (95% CI, 53.8-70.1) for subjects from a high (95th percentile) neighborhood.",
            "output": [
                "Is neighborhood of residence associated with daily adherence to CPAP therapy?"
            ]
        },
        {
            "id": "task847-965f2f60f8aa431598570adbdaa19589",
            "input": "Patients with chronic viral hepatitis are at a higher risk for cognitive dysfunction. Little is known about the association between hepatitis A virus (HAV) infection and cognitive function.', 'From the National Health and Nutrition Examination Survey, 1999-2002, we selected study participants (> or =60 years, n = 1,529) without hepatitis B, C, or D virus infection; without previous hepatitis A vaccination; and without abnormal liver function. HAV-seropositive participants represented people with previous HAV infection. Psychomotor speed and executive functioning domain of cognitive function were measured by the Digit Symbol Substitution Test (DSST).', 'HAV-seropositive participants had lower DSST scores than HAV-seronegative participants (weighted mean, 44.4 vs 53.9, p < .001). We designated HAV-seronegative participants as the reference group. Univariate analysis demonstrated that the weighted beta coefficient of DSST score was -9.55 (95% confidence interval [CI] -9.57 to -9.54, p < .001) for the HAV-seropositive participants. In a multivariable model, the weighted adjusted beta coefficient of DSST score was -2.48 (95% CI -2.49 to -2.46, p < .001) for the HAV-seropositive participants.",
            "output": [
                "Is previous hepatitis a virus infection related to slower psychomotor speed in elderly adults?"
            ]
        },
        {
            "id": "task847-749f6e7a9828477393564d9e3ce5f617",
            "input": "Endoscopic endonasal surgery let us observe that woodworkers' nasal adenocarcinomas originate in the olfactory cleft. Our aim was the identification of CT imaging features that corroborate the olfactory cleft as the site of origin for woodworkers' adenocarcinoma.\", 'We designed a retrospective study to compare CT scans of 27 unilateral olfactory cleft adenocarcinomas with 30 cases of nasosinusal polyposis (NSP) and 33 healthy sinus controls. Enlargement of the olfactory cleft, lateralization of the ethmoidal turbinate wall, and contralateral bulging of the nasal septum were measured on coronal scans passing through crista galli and posterior half of both ocular globes. Comparisons have been performed by using analysis of variance and the Bonferroni procedure.', 'The nasal septum was significantly bulging across the midline in adenocarcinoma (4.6 +/- 3 mm; range, -0.1-13.7 mm) compared with NSP (0.7 +/- 1 mm; range, -2.1-2.3 mm) or healthy sinus controls (0.5 +/- 1 mm; range, -1.2-2 mm) (P < .001). The olfactory cleft was significantly wider in adenocarcinoma (15.1 +/- 4.5 mm; range, 8.6-25.7 mm) than in NSP (3.6 +/- 0.4 mm; range, 2.8-4.6 mm) or healthy sinus controls (3.3 +/- 0.7 mm; range, 1.4-4.6 mm). The ethmoidal labyrinth width was significantly smaller on the pathologic side in adenocarcinoma (7.2 +/- 2.7 mm; range, 3.2-14.2 mm) than in the control groups (P < .001). Whereas the angle between the conchal lamina and vertical midline was close to zero degrees in NSP (0.03 +/- 2.25 degrees ; range, -5 degrees -3 degrees ) and healthy sinus controls (0.45 +/- 2.13 degrees , range, -5 degrees -5 degrees ), it reached 39.76 +/- 13.83 degrees (P < .001) in adenocarcinoma.",
            "output": [
                "Does cT assessment of woodworkers ' nasal adenocarcinomas confirm the origin in the olfactory cleft?"
            ]
        },
        {
            "id": "task847-66c739684a9d43a2b15d8b332dee866d",
            "input": "Activated protein C (APC) is a plasma serine protease with systemic anticoagulant and a wide spectrum of cytoprotective activities that has been proposed as a promising therapy for acute stroke. Therefore, we sought to investigate the role of endogenous APC in human ischemic stroke.', 'Our target were 119 consecutive patients with an ischemic stroke involving the middle cerebral artery territory who received tissue plasminogen activator (t-PA) within 3 h of symptom onset. APC was measured before, as well as 1 and 2 h after t-PA administration, and again at 12 and 24 h after stroke onset. Cranial tomography scan was obtained at admission and repeated at 24-48 h or when a neurological worsening occurred to rule out the presence of hemorrhagic complications. The functional outcome was evaluated by 3-month modified Rankin Scale.', 'A total of 117 t-PA-treated patients were finally included in the analyses. APC peaked at 1 h after t-PA administration (pretreatment APC = 132.44 +/- 36.39%, 1-hour APC = 184.20 +/- 34.28%, 2-hour APC = 145.50 +/- 35.23%; p < 0.0001). Interestingly, a high 2-hour APC level was associated with parenchymal hemorrhages (OR = 25.19; 95% CI = 4.76-133.19; p = 0.0001) and mortality (OR = 13.8; 95% CI = 2.58-73.63; p = 0.001), in a logistic regression model. Our results remained significant after Bonferroni correction for multiple testing.",
            "output": [
                "Does endogenous activated protein C predict hemorrhagic transformation and mortality after tissue plasminogen activator treatment in stroke patients?"
            ]
        },
        {
            "id": "task847-f8106c05ebc940d89b612acb04f14deb",
            "input": "Celastrol is an active ingredient of traditional herbal medicine and has recently been identified as a potent natural proteasome inhibitor. In the present study, we evaluated the radiosensitizing potential of celastrol in the human prostate cancer PC-3 model.', 'Clonogenic assays were performed to determine the radiosensitizing effect of celastrol. Apoptosis was examined by flow cytometry using Annexin V and propidium iodide staining and by a caspase-3 activation assay. DNA damage processing was examined by immunofluorescent staining and Western blot for phosphorylated H2AX (gammaH2AX). The PC-3 xenograft model in the athymic nude mouse was used for the determination of the in vivo efficacy of celastrol combined with radiotherapy. The tumor samples were also analyzed for apoptosis and angiogenesis.', 'Celastrol sensitized PC-3 cells to ionizing radiation (IR) in a dose- and schedule-dependent manner, in which pretreatment with celastrol for 1 h followed by IR achieved maximal radiosensitization. Celastrol significantly prolonged the presence of IR-induced gammaH2AX and increased IR-induced apoptosis. Celastrol, combined with fractionated radiation, significantly inhibited PC-3 tumor growth in vivo without obvious systemic toxicity. The combination treatment increased gammaH2AX levels and apoptosis, induced cleavage of poly(adenosine diphosphate-ribose)polymerase and Mcl-1, and reduced angiogenesis in vivo compared with either treatment alone.",
            "output": [
                "Does celastrol potentiate radiotherapy by impairment of DNA damage processing in human prostate cancer?"
            ]
        },
        {
            "id": "task847-f1eead5dd8b9455ebfb92a0fbc7d3cc5",
            "input": "This study sought to determine how esthetic appearance of babies may affect their motivational processing by the adults.', \"Healthy men and women were administered two laboratory-based tasks: a) key pressing to change the viewing time of normal-looking babies and of those with abnormal facial features (e.g., cleft palate, strabismus, skin disorders, Down's syndrome and fetal alcohol syndrome) and b) attractiveness ratings of these images. Exposure to the babies' images produced two different response patterns: for normal babies, there was a similar effort by the two groups to extend the visual processing with lower attractiveness ratings by men; for abnormal babies, women exerted greater effort to shorten the viewing time despite attractiveness ratings comparable to the men.",
            "output": [
                "Are gender differences in the motivational processing of babies determined by their facial attractiveness?"
            ]
        },
        {
            "id": "task847-771576ee3c30483186e196ea4b4826fc",
            "input": "A small subset (10-15%) of gastrointestinal stromal tumours (GISTs) lack mutations in KIT and PDGFRA (wild-type GIST). Recently, a novel BRAF exon 15 mutation (V600E) was detected in imatinib-naive wild-type high-risk intestinal GISTs (4%). However, the frequency and distribution of BRAF mutations within the spectrum of GISTs, and whether they might represent secondary events acquired during tumour progression, remain unknown.', '69 GISTs (39 KIT mutants, 2 PDGFRA mutants and 28 wild-type) were analysed for mutations in BRAF exon 15 and KRAS exon 2. To assess the stage at which these mutations might occur in GIST, a considerable number of incidental gastric (n = 23) and intestinal (n = 2) tumours were included.', 'BRAF mutations (V600E) were detected in 2 of 28 wild-type GISTs (7%), but in none of the 41 KIT/PDGFRA mutants. No KRAS mutation was detected. The two BRAF-mutated GISTs measured 4 mm in diameter and originated in the gastric body and the jejunum in two men (mean age, 76 years). Both tumours were mitotically inactive KIT-positive spindle-cell GISTs that were indistinguishable histologically from their more common KIT-mutated counterparts.",
            "output": [
                "Are v600E BRAF mutations alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours?"
            ]
        },
        {
            "id": "task847-3a53e550e0134af89ad4694fc5c00d56",
            "input": "Recent whole genome association studies have independently identified multiple prostate cancer (PC) risk variants on 8q24. We have evaluated association of common variants in this region with PC susceptibility and tumor aggressiveness in a sample of European American men.', \"Forty-nine tagging SNPs including three previously reported significant variants (rs1447295, rs6983267, rs16901979) and seven variants in the 5' upstream region of the MYC proto-oncogene were tested for association with susceptibility to PC and tumor aggressiveness in 596 histologically verified PC cases and 567 ethnically matched controls.\", 'Significant associations with susceptibility to PC were found at 17 SNPs, four of which (rs1016342, rs1378897, rs871135, and rs6470517) remained significant after adjusting for multiple corrections. One of the associated SNPs, rs871135, is located in the putative gene POU5F1P1 within the 8q24 region. An in slico analysis showed that the associated variant of this SNP alters a transcription factor implicating a plausible regulatory role. Additionally, one of the significantly associated SNPs, rs6470517, with PC susceptibility showed a significant over-representation of the G allele in cases with aggressive tumor.",
            "output": [
                "Are common variants in 8q24 associated with risk for prostate cancer and tumor aggressiveness in men of European ancestry?"
            ]
        },
        {
            "id": "task847-debf861a45f24043b908eb64c979bde9",
            "input": "Our study was designed to find whether a change in physician ordering of laboratory testing could be obtained by the simple strategy of changing the set-up of the check-box laboratory order form that is embedded in a computerized medical record.', 'This prospective intervention study was undertaken in Maccabi Healthcare Services, a Preferred Provider Organization that has used a computerized medical record since 1992. We examined data from 865 primary healthcare physicians over 3 years. In May 2005 we changed the order form and reduced the number of tests that can be ordered using a check-box form from 51 to 26. Twenty-seven tests were removed from the form and two tests were added. The total number of laboratory test orders and the median rate of test orders per visit to physician during each of the study periods were calculated separately for each test.', 'Tests that were added to the computerized laboratory order form showed an increase of 60.7% in the first year and a further 90% increase in the following year. For the unchanged tests the percentage changes over the same periods were +18.4% and -22.4%. For the deleted tests the change was -27% and -19.2% for the respective years.",
            "output": [
                "Does format change of a laboratory test order form affect physician behavior?"
            ]
        },
        {
            "id": "task847-ba2e1884eaab44c4a93629407a5017b6",
            "input": "Goblet cell hyperplasia with mucus hypersecretion contribute to increased morbidity and mortality in bronchial asthma. We have reported that thioredoxin 1 (TRX1), a redox (reduction/oxidation)-active protein acting as a strong antioxidant, inhibits pulmonary eosinophilic inflammation and production of chemokines and Th2 cytokines in the lungs, thus decreasing airway hyperresponsiveness (AHR) and airway remodeling in mouse asthma models. In the present study, we investigated whether endogenous or exogenous TRX1 inhibits goblet cell hyperplasia in a mouse asthma model involving chronic exposure to antigen.', 'We used wild-type Balb/c mice and Balb/c background human TRX1-transgenic mice constitutively overproducing human TRX1 protein in the lungs. Mice were sensitized 7 times (days 0 to 12) and then challenged 9 times with ovalbumin (OVA) (days 19 to 45). Every second day from days 18 to 44 (14 times) or days 35 to 45 (6 times), Balb/c mice were treated with 40 microg recombinant human TRX1 (rhTRX1) protein. Goblet cells in the lungs were examined quantitatively on day 34 or 45.', 'Goblet cell hyperplasia was significantly prevented in TRX1-transgenic mice in comparison with TRX1 transgene-negative mice. rhTRX1 administration during OVA challenge (days 18 to 44) significantly inhibited goblet cell hyperplasia in OVA-sensitized and -challenged wild-type mice. Moreover, rhTRX1 administration after the establishment of goblet cell hyperplasia (days 35 to 45) also significantly ameliorated goblet cell hyperplasia in OVA-sensitized and -challenged wild-type mice.",
            "output": [
                "Does endogenous and exogenous thioredoxin 1 prevent goblet cell hyperplasia in a chronic antigen exposure asthma model?"
            ]
        },
        {
            "id": "task847-8c65a3cbb0994ec5940918c46235df64",
            "input": "Ag-dependent activation of IgE-bearing mast cells is a critical first step in immediate hypersensitivity and other allergic responses. Recent studies have revealed Ag-independent effects of monoclonal mouse IgE molecules on mast cell survival and activation. However, no studies have been performed on the effects of polyclonal IgE molecules. Here, we tested whether polyclonal mouse and human IgE molecules affect survival and cytokine production in mast cells.', 'Mast cells were cultured in the presence of polyclonal mouse and human IgE molecules, and cell survival and cytokine production were analyzed.', 'Polyclonal mouse IgE molecules in sera from mice with atopic dermatitis-like allergic skin inflammation, enhanced survival and cytokine production in mast cell cultures. Similar to the effects of monoclonal IgE, the polyclonal IgE effects were mediated by the high-affinity IgE receptor, FcepsilonRI. Human polyclonal IgE molecules present in sera from atopic dermatitis patients were also capable of activating mast cells, and inducing IL-8 production in human cord blood-derived mast cells.",
            "output": [
                "Does polyclonal IgE induce mast cell survival and cytokine production?"
            ]
        },
        {
            "id": "task847-d288b52af3af48d3b79ea7fcac96e5ab",
            "input": "Dupuytren's Disease (DD) is a debilitating contractile fibrosis of the palmar fascia characterised by excess collagen deposition, contractile myofibroblast development, increased transforming growth factor-beta levels and beta-catenin accumulation. The aim of this study was to determine if a collagen-enriched environment, similar to in vivo conditions, altered beta-catenin accumulation by primary DD cells in the presence or absence of transforming growth factor-beta.\", 'Primary DD and patient matched, phenotypically normal palmar fascia (PF) cells were cultured in the presence or absence of type-1 collagen and transforming growth factor-beta1. beta-catenin and alpha-smooth muscle actin levels were assessed by western immunoblotting and immunofluorescence microscopy.', 'DD cells display a rapid depletion of cellular beta-catenin not evident in patient-matched PF cells. This effect was not evident in either cell type when cultured in the absence of type-1 collagen. Exogenous addition of transforming growth factor-beta1 to DD cells in collagen culture negates the loss of beta-catenin accumulation. Transforming growth factor-beta1-induced alpha-smooth muscle actin, a marker of myofibroblast differentiation, is attenuated by the inclusion of type-1 collagen in cultures of DD and PF cells.",
            "output": [
                "Does type-1 Collagen differentially alter beta-catenin accumulation in primary Dupuytren 's Disease cord and adjacent palmar fascia cells?"
            ]
        },
        {
            "id": "task847-859c63755c8243d18b0e325dbd1674ae",
            "input": "Genetic polymorphisms that modify the detoxifying activity of glutathione S-transferases (GSTs) can affect the level of carcinogenic metabolites created by endogenous steroid hormones and exogenous chemical substances. Although the GSTM1 null genotype has been shown to increase prostate cancer mortality in Caucasians, potential associations between GST polymorphisms and prostate cancer biochemical recurrence (BCR) have not been well studied, particularly in African-Americans.', 'We examined potential associations between the GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and BCR, after prostatectomy, in 168 African-American and 226 Caucasian patients treated at Henry Ford Hospital in Detroit, Michigan using Cox proportional hazards modeling.', 'We found that African-Americans with the GSTT1 null genotype had increased BCR risk compared to those having GSTT1 present (hazard ratio (HR) = 2.30; 95% CI = 1.01\u20135.18; p = 0.04); and African-Americans with the GSTT1 null genotype and high grade tumors had an even greater risk (HR = 7.82; 95% CI = 2.49\u201324.50; p < 0.001). In Caucasians, an increased risk was observed in those patients with high grade tumors and the GSTM1 null genotype (HR = 2.88; 95% CI = 1.16\u20137.14; p = 0.02). Similar associations were observed for advanced stage and more aggressive (high grade or advanced stage) disease.",
            "output": [
                "Do polymorphisms in glutathione S-transferase genes increase risk of prostate cancer biochemical recurrence differentially by ethnicity and disease severity?"
            ]
        },
        {
            "id": "task847-c68c2555f94249ad952a7892ea83e790",
            "input": "Temporo-parietal theta activity (TPTA), often detected in hemispheres with internal carotid (ICA) or middle cerebral artery (MCA) occlusive lesions, is more clearly separated from occipital alpha activity by magnetoencephalography (MEG) than electroencephalography. The present study investigated whether TPTA is correlated with misery perfusion, a surgically correctable type of hemodynamic impairment.', 'Awake MEG was measured in 56 patients with ICA or MCA occlusive lesions. Regional cerebral blood flow (rCBF) and regional cerebrovascular reactivity (rCVR) to acetazolamide were measured in the MCA territory by xenon-133 single-photon emission computed tomography. MEG was repeated in 10 patients after vascular reconstruction surgery.', 'Fourteen patients showed TPTA in the lesion hemisphere (n=13) or bilaterally (n=1). The presence of TPTA was significantly correlated with both reduced rCBF and reduced rCVR (P=0.0009). After surgery, TPTA disappeared in 7 of the 10 studied patients.",
            "output": [
                "Does temporo-parietal theta activity correlate with misery perfusion in arterial occlusive disease?"
            ]
        },
        {
            "id": "task847-ce06292e057b4b5f8d10bb341d1f90b8",
            "input": "Chronic inflammation and remodeling of the bronchial wall are basic hallmarks of asthma. It is known that mesenchymal cells in the lamina reticularis underlying the basement membrane of the thickened airway wall of asthmatics predominantly display the phenotype of myofibroblasts and express alpha-smooth muscle actin (alpha-SMA). Human bronchial fibroblasts (HBFs) transform in vitro into myofibroblasts under the influence of transforming growth factor (TGF-beta). Differences in the reactivity of fibroblasts to TGF-beta in cultures derived from healthy and asthmatic donors are elucidated here.', 'Primary human bronchial fibroblasts (HBFs) were cultured from bronchial biopsies from non-asthmatic (n=7) and asthmatic (n=7) donors and treated with TGF-beta1 or TGF-beta2 to induce myofibroblast differentiation. Expression of alpha-smooth muscle actin (alpha-SMA) was assessed by immunocytochemistry and Western blotting. The cell size and shape parameters were measured by computer-aided methods.', 'Regardless of whether TGF-beta1 or TGF-beta2 was used, asthmatic cells showed enhanced expression of the myofibroblast marker as confirmed by immunocytochemistry and immunoblotting. Analysis of the shape parameters of cells incubated in the presence of TGF-beta1 revealed that HBFs of asthmatics differ from those of non-asthmatics.",
            "output": [
                "Do asthmatic bronchial fibroblasts demonstrate enhanced potential to differentiate into myofibroblasts in culture?"
            ]
        },
        {
            "id": "task847-f4f14011b43642c19484f36a0933e855",
            "input": "The relationship of bipolar disorder (BD) and altered thyroid function is increasingly recognized. Recently, a behavioral phenotype of co-occurring deviance on the Anxious/Depressed (A/D), Attention Problems (AP), and Aggressive Behavior (AB) syndrome scales has been identified as the Child Behavior Checklist Dysregulation Profile (CBCL-DP), which itself has been linked to BD. This study tested for differences in thyroid function within a sample of n=114 psychiatric children and adolescents with and without the CBCL-DP.', 'A CBCL-DP score was generated based on the composite of the crucial CBCL syndrome scales (A/D, AP, AB). Participants with a CBCL-DP score >or=2.5 SDs above average constituted the CBCL-DP subgroup (n=53). Those with CBCL-DP scores of 1 SD or less above average percentile were regarded as controls (n=61). Groups were compared regarding serum levels of TSH, fT3 and fT4.', 'In participants showing the CBCL-DP, basal serum TSH was elevated compared to controls. More CBCL-DP subjects than controls showed subclinical hypothyroidism. No differences were observed for serum fT3 and fT4 levels.",
            "output": [
                "Is severe affective and behavioral dysregulation in youth associated with increased serum TSH?"
            ]
        },
        {
            "id": "task847-7e959f6f6ae44b44a5100d37a9f4cb24",
            "input": "Sputum Gram stain and culture have been said to be unreliable indicators of the microbiological diagnosis of bacterial pneumonia. The etiological diagnosis of pneumonia is surrounded by great degree of uncertainty. This uncertainty should be and can be calculated and incorporated in the diagnosis and treatment.', 'To determine the diagnostic accuracy and diagnostic value of sputum Gram stain in etiological diagnosis and initial selection of antimicrobial therapy of bacterial community acquired pneumonia (CAP). DESIGN-METHOD: Prospective study of 1390 patients with CAP admitted January 2002-June 2008, to our institutions. Of the 1390 patients, 178 (12.8%) fulfilled the criteria for inclusion into this study (good-quality sputa and presence of the same microorganism in blood and sputum cultures which was used as gold standard for assessing the diagnostic accuracy and diagnostic value of sputum Gram stain).', 'The sensitivity of sputum Gram stain was 0.82 for Pneumococcal pneumonia, 0.76 for Staphylococcal pneumonia, 0.79 for Haemophilus influenzae pneumonia and 0.78 for Gram-negative bacilli pneumonia. The specificity of sputum Gram stain was 0.93 for Pneumococcal pneumonia, 0.96 for Staphylococcal pneumonia, 0.96 for H. influenzae pneumonia and 0.95 for Gram-negative bacilli pneumonia. The positive likelihood ratio (LR+) was 11.58 for Pneumococcal pneumonia, 19.38 for Staphylococcal pneumonia, 16.84 for H. influenzae pneumonia, 14.26 for Gram-negative bacilli pneumonia. The negative likelihood ratio (LR-) was 0.20 for Pneumococcal pneumonia, 0.25 for Staphylococcal pneumonia, 0.22 for H. influenzae pneumonia, and 0.23 for Gram-negative bacilli pneumonia.",
            "output": [
                "Do a prospective study of the diagnostic utility of sputum Gram stain in pneumonia?"
            ]
        },
        {
            "id": "task847-76319a0ee4374571839b18af0af5b1f3",
            "input": "Transcranial Doppler (TCD) ultrasound is a procedure commonly used to screen individuals with the major hemoglobin S diseases, Hb SS and Hb S-beta(0), for significant stenoses in the circle of Willis. Flow velocities above 200 cm/s have been shown to identify patients at elevated risk for cerebral infarction. Among TCD's limitations is the inability to insonate the distal extracranial, petrous, and cavernous internal carotid artery (ICA) through the standard transtemporal approach.\", 'We extended the submandibular approach to include infra-siphon portions of the ICA.', 'Using the extended submandibular approach to evaluate these portions of the ICA, we identified stenotic lesions in 4 patients with Hb SS disease out of a population of 131 children with Hb SS. Three of the 4 patients had no history of overt stroke or stroke-like symptoms. Neuroimaging confirmed the stenotic lesions, and also revealed watershed infarction as well as discrete areas of silent infarction. All 4 children had neuropsychological impairment.",
            "output": [
                "Does submandibular TCD approach detect post-bulb ICA stenosis in children with sickle cell anemia?"
            ]
        },
        {
            "id": "task847-c2404754b30d49ddb788cf317ad0575f",
            "input": "We hypothesized that ultrasound characteristics of breast fibroadenomas (FA) vary in relation to the clinical and histological parameters: patient age, tumor size and histological classification.', 'Eleven ultrasound characteristics frequently observed in breast tumors were defined before the onset of our study. These characteristics, as well as a semi-quantitative score for vascularization on color-coded Doppler ultrasound, were analyzed in a retrospective study. Histology revealed adult type differentiation in all FA. They were divided into florid, regressive and mixed subtypes. The examiner was blinded for the histological classification during image analysis.', 'Histological type: florid FA: more frequent in younger women (age group < 30 years; p < 0.001), and bigger than regressive FA (larger than 16 mm: p = 0.007). Statistically significant differences between florid and regressive FA regarding the ultrasound features: enhanced posterior ultrasound transmission (p < 0.001), homogenous echo pattern (p = 0.003) and lobulated margin contour (p = 0.042). Tumor size: patients with larger tumors (> 16 mm) were younger (mean age 35 vs. 43 years, p < 0.001). More often in bigger FA: enhanced dorsal ultrasound transmission (p < 0.001), hyperechoic spots (p < 0.001), strong vascularization (p < 0.001), inhomogeneous echo pattern (p = 0.001), horizontal axis (p = 0.009), lobulated margin contour (p = 0.009), lateral shadowing (p = 0.047). Age: more often in older patients (age group > 30 years): dorsal ultrasound shadowing (p = 0.008), irregular margin contour (p = 0.038), homogenous echo pattern (p = 0.047).",
            "output": [
                "Are ultrasound characteristics of breast fibroadenomas related to clinical and histological parameters?"
            ]
        },
        {
            "id": "task847-fd87f0b0dab5417fa4203b356ad25dd0",
            "input": "To measure the prevalence, predictors, and posthospitalization outcomes associated with the overlap syndrome of coexisting depression and incident delirium in older hospitalized patients.', 'Secondary analysis of prospective cohort data from the control group of the Delirium Prevention Trial.', 'General medical service of an academic medical center. Follow-up interviews at 1 month and 1 year post-hospital discharge.', 'Four hundred fifty-nine patients aged 70 and older who were not delirious at hospital admission.', 'Depressive symptoms assessed at hospital admission using the 15-item Geriatric Depression Scale (cutoff score of 6 used to define depression), daily assessments of incident delirium from admission to discharge using the Confusion Assessment Method, activities of daily living at admission and 1 month postdischarge, and new nursing home placement and mortality determined at 1 year.', 'Of 459 participants, 23 (5.0%) had the overlap syndrome, 39 (8.5%) delirium alone, 121 (26.3%) depression alone, and 276 (60.1%) neither condition. In adjusted analysis, patients with the overlap syndrome had higher odds of new nursing home placement or death at 1 year (adjusted odds ratio (AOR)=5.38, 95% confidence interval (CI)=1.57-18.38) and 1-month functional decline (AOR=3.30, 95% CI=1.14-9.56) than patients with neither condition.",
            "output": [
                "Do the overlap syndrome of depression and delirium in older hospitalized patients?"
            ]
        },
        {
            "id": "task847-d4b608d97ad246309bb9a697ba8af720",
            "input": "Cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites or recurrent variceal bleeding are at risk for decompensation and death. This study examined whether a new model for end stage liver disease (MELD), which incorporates serum sodium (MELDNa), is a better predictor of death or transplant after TIPS than the original MELD.', \"One hundred forty-eight consecutive patients undergoing nonemergent TIPS for refractory ascites or recurrent variceal bleeding from 1997 to 2006 at a single center were evaluated retrospectively. Cox model analysis was performed with death or transplant within 6 months as the end point. The models were compared using the Harrell's C index. Recursive partitioning determined the optimal MELDNa cutoff to maximize the risk:benefit ratio of TIPS.\", 'The predictive ability of MELDNa was superior to MELD, particularly in patients with low MELD scores. The C indices (95% confidence interval [CI]) for MELDNa and MELD were 0.65 (95% CI, 0.55-0.71) and 0.58 (95% CI, 0.51-0.67) using a cut-off score of 18, and 0.72 (95% CI, 0.60-0.85) and 0.62 (95% CI, 0.49-0.74) using a cut-off score of 15. Using a MELDNa >15, 22% of patients were reclassified to a higher risk with an event rate of 44% compared with 10% when the score was <or=15.",
            "output": [
                "Does new model for end stage liver disease improve prognostic capability after transjugular intrahepatic portosystemic shunt?"
            ]
        },
        {
            "id": "task847-c48e867b6dff40319967271c27325464",
            "input": "Although chronic pancreatitis and liver cirrhosis are common sequelae of excess alcohol consumption, the 2 conditions are rarely associated. We studied the prevalence of simultaneous liver cirrhosis and chronic pancreatitis in alcoholics.', 'Postmortem autopsy data from 620 individuals with a history of excess alcohol consumption and 100 nonalcoholics (controls) were analyzed. The individuals were classified into groups based on macroscopic observations of pancreas (no injury, acute pancreatitis, fibrosis, and chronic pancreatitis) and liver (no injury, moderate steatosis, severe steatosis, and cirrhosis). The same classification system was used for histological data, which was used to confirm and correlate macroscopic results.', 'Out of the 183 patients with liver cirrhosis, 33 (18%) had chronic pancreatitis and 93 (51%) had pancreatic fibrosis. Out of the 230 patients with severe steatosis, 37 (16%) had chronic pancreatitis and 97 (42%) were found to have a pancreatic fibrosis. Thirty-three (39%) with chronic pancreatitis also showed liver cirrhosis and 37 (44%) showed severe steatosis. Thirty-eight percent of the patients with a pancreatic fibrosis were found also to have liver cirrhosis and in another 40% severe steatosis. Thirty-five patients showed neither hepatic or pancreatic injury. We found no chronic pancreatitis or liver cirrhosis in the control group (n = 100).",
            "output": [
                "Are pancreas and liver injury associated in individuals with increased alcohol consumption?"
            ]
        },
        {
            "id": "task847-04935e10290540298cebf52df809898c",
            "input": "The adipokine chemerin modulates the function of innate immune cells and may link obesity and inflammation, and therefore, a possible relation of chemerin to inflammatory proteins in obesity and type 2 diabetes (T2D) was analysed. As visceral fat contributes to systemic inflammation, chemerin was measured in portal venous (PVS), hepatic venous (HVS) and systemic venous (SVS) blood of patients with liver cirrhosis.', 'Systemic chemerin was determined by ELISA in the serum of normal-weight, overweight and T2D males, in the serum of T2D patients of both sexes, and in PVS, HVS and SVS of patients with liver cirrhosis.', 'Circulating chemerin was similar in T2D and obese individuals but was significantly elevated in both cohorts compared to normal-weight individuals. Chemerin positively correlated with leptin, resistin and C-reactive protein (CRP). In T2D, chemerin was similar in male and female patients and increased in patients with elevated CRP. Chemerin was similar in PVS and SVS, indicating that visceral fat is not a major site of chemerin synthesis. Higher levels of chemerin in HVS demonstrate that chemerin is also released by the liver.",
            "output": [
                "Is systemic chemerin related to inflammation rather than obesity in type 2 diabetes?"
            ]
        },
        {
            "id": "task847-dd8d3f2ad759486ea9ca741fa916b7ac",
            "input": "Platinum-based concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced unresectable non-small cell lung cancer (NSCLC). The determination of parameters that may predict the result of the treatment has strong clinical implications.', 'Pretreatment tumor biopsy specimens from 39 patients with locally advanced NSCLC (stage IIIA: 5, stage IIIB: 34) were analyzed for p53, Bcl-2, Bax and ERCC1 expression by immunohistochemistry. All patients were treated with cisplatin-based CCRT. Twenty-four patients received induction chemotherapy followed by CCRT (60Gy/30 fractions, 6mg/m(2) of cisplatin daily). The most commonly administered induction chemotherapy regimen was VIP (etoposide, ifosfamide, cisplatin; 20 patients). Fifteen patients received the same CCRT without induction chemotherapy.', 'High expression of p53, Bcl-2, Bax and ERCC1 was observed in 15 (38%), 19 (49%), 17 (44%) and 12 (31%) patients, respectively. High expression of Bcl-2 was significantly associated with longer survival duration (20 months vs. 9 months, P=0.008) and better response to the treatment (74% vs. 30%, P=0.01). In multivariate analysis, Bcl-2 expression was the only significant independent prognostic factor of overall survival (P=0.007) among the pretreatment patients characteristics.",
            "output": [
                "Does expression of Bcl-2 predict outcome in locally advanced non-small cell lung cancer patients treated with cisplatin-based concurrent chemoradiotherapy?"
            ]
        },
        {
            "id": "task847-9d09d6d3df1c4b7d91bb803745d67608",
            "input": "Concomitant thyroid nodules are the most common reason for false-positive ultrasonography (US) results in primary hyperparathyroidism. The aims of this prospective clinical study were to evaluate false-positive US results according to the characteristics of concomitant thyroid nodules and to determine which characteristics of thyroid nodules are important.', 'This prospective study included 120 consecutive patients with primary hyperparathyroidism. The patients were divided into 2 groups according to preoperative US results. Group 1 consisted of 32 patients with false-positive US results and group 2 consisted of 88 patients with true-positive US results.', 'The risk for false-positive US result was increased 25-fold for patients with parathyroid adenoma weight of more than 500 mg (odds ratio [OR], 25; 95% confidence interval [CI], 8.6-74.5), 75-fold for more than 1 posteriorly located thyroid (OR, 75; 95% CI, 19.3-293.4), 358-fold for the presence of exophytic thyroid nodules (OR, 358; 95% CI, 42.3-3036), and 423-fold for the presence of posteriorly located thyroid nodules (OR, 423; 95% CI, 49-3662).",
            "output": [
                "Do the characteristics of concomitant thyroid nodules cause false-positive ultrasonography results in primary hyperparathyroidism?"
            ]
        },
        {
            "id": "task847-c23c779b2f134286a63a3a92cb975cc8",
            "input": "Human bocavirus (HBoV) is a newly identified human parvovirus that was originally detected in the respiratory secretions of children with respiratory infections. This study aimed to learn about the importance of HBoV infections by revealing the prevalence of serum antibodies against HBoV in Beijing population.', 'Two batches of serum specimens collected in different periods were tested by Western blotting for specific IgG against HBoV using recombinant VP2 as antigen.', 'Out of 677 serum specimens collected during April 1996 to March 1997, 400 (59.1%) were positive and antibody positive rate for another batch of 141 serum specimens collected in August, 2005 from adults aged from 20 years to over 60 years was 78.7% (111/141). Comparison of the sero-prevalence profiles for serum specimens collected during 1996 - 1997 to those collected in 2005 indicated that the antibody positive rate for specimens collected in 2005 was higher than that of the corresponding age groups collected during 1996 - 1997.",
            "output": [
                "Are human bocavirus infections common in Beijing population indicated by sero-antibody prevalence analysis?"
            ]
        },
        {
            "id": "task847-b80d63e7e5d94a84b08314a9669d4939",
            "input": "Minute ventilation (MV) has been proven to be very useful in rate responsive pacing. The aim of this study was to evaluate the feasibility of using implantable cardioverter-defibrillator (ICD) leads as part of the MV detection system.', 'At implant in 10 patients, the transthoracic impedance was measured from tripolar ICD, tetrapolar ICD, and atrial lead vectors during normal, deep, and shallow voluntary respiration. MV and respiration rate (RespR) were simultaneously measured through a facemask with a pneumotachometer (Korr), and the correlations with impedance-based measurements were calculated. Air sensitivity was the change in impedance per change in respiratory tidal volume, ohms (Omega)/liter (L), and the signal-to-noise ratio (SNR) was the ratio of the respiratory and cardiac contraction components.', 'The air sensitivity and SNR in tripolar ICD vector were 2.70 +/- 2.73 ohm/L and 2.19 +/- 1.31, respectively, and were not different from tetrapolar. The difference in RespR between tripolar ICD and Korr was 0.2 +/- 1.91 breaths/minute. The regressed correlation coefficient between impedance MV and Korr MV was 0.86 +/- 0.07 in tripolar ICD.",
            "output": [
                "Does acute evaluation of transthoracic impedance vectors using ICD lead?"
            ]
        },
        {
            "id": "task847-9720322ece1940c9bb2bcfc97b81c3ec",
            "input": "Globally, heterosexual intercourse is the primary route of HIV-1 (HIV) transmission. It follows that mechanisms that protect against HIV infection are likely operative at the genital mucosa. In HIV-resistant Kenyan sex workers who are highly exposed to HIV infection yet remain uninfected, protection correlates with HIV-specific immune responses and genetic factors. However, these factors do not entirely explain this model of natural immunity to HIV. We hypothesized that protection may be mediated by innate immune proteins in the genital tract of HIV-resistant sex workers.', 'The genital proteome of mucosal secretions from HIV-resistant women was examined using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Cervical lavage samples were collected from 315 HIV-resistant, HIV-uninfected and HIV-infected commercial sex workers.', 'Univariate analysis identified a 6 kDa biomarker of HIV resistance in genital secretions from these women. This protein was identified by tandem mass spectrometry as elafin and was found to be overexpressed in HIV-resistant women compared with HIV-uninfected (P = 0.001) and infected (P = 0.002) women. The elevated levels of elafin/trappin-2 in HIV-resistant women were confirmed using ELISA. The prospective association of elevated cervicovaginal elafin/trappin-2 levels with protection from HIV acquisition was then confirmed in an independent cohort of high-risk female sex workers.",
            "output": [
                "Does elevated elafin/trappin-2 in the female genital tract is associate with protection against HIV acquisition?"
            ]
        },
        {
            "id": "task847-c0f03fccd6d84701b4ead324dc95ce28",
            "input": "Acute nonvariceal upper-GI hemorrhage (NVUGIH) is associated with significant morbidity and mortality.', 'To examine the relationship between hospital volume and outcomes of NVUGIH.', 'A cross-sectional study.', 'Participating hospitals from the Nationwide Inpatient Sample 2004.', 'All discharged patients with a primary discharge diagnosis of NVUGIH based on the International Classification of Diseases, Clinical Modification, ninth edition codes.', 'Patients were divided into 3 groups based on discharge from hospitals with annual discharge volumes of 1 to 125 (low), 126 to 250 (medium), and >250 (high).', 'In-hospital mortality, length of stay, and hospitalization charges.', 'The study included a total of 135,366, 132,746, and 123,007 discharges with NVUGIH occurred from low-volume, medium-volume, and high-volume hospitals, respectively. On multivariate analysis, when adjusting for age, comorbidity, and the presence of complications, patients at high-volume hospitals had significantly lower in-hospital mortality (odds ratio [OR] 0.85 [95% CI, 0.74-0.98]) than patients at low-volume hospitals. Patients at high-volume hospitals were also more likely to undergo upper-GI endoscopy (OR 1.52 [95% CI, 1.36-1.69]) or early endoscopy within 1 day of hospitalization compared with low-volume hospitals (60.5% vs 53.8%, adjusted OR 1.28 [95% CI, 1.02-1.61]). Undergoing endoscopy within day 1 was associated with shorter hospital stays (-1.08 days [95% CI, -1.24 to -0.92 days]) and lower hospitalization charges (-$1958 [95% CI, -$3227 to -$688]).",
            "output": [
                "Is higher hospital volume associated with lower mortality in acute nonvariceal upper-GI hemorrhage?"
            ]
        },
        {
            "id": "task847-3eb2319add58428895d518de16356fe6",
            "input": "Raf Kinase Inhibitory Protein (RKIP, also PEBP1), a member of the Phosphatidylethanolamine Binding Protein family, negatively regulates growth factor signaling by the Raf/MAP kinase pathway. Since an organic compound, locostatin, was reported to bind RKIP and inhibit cell migration by a Raf-dependent mechanism, we addressed the role of RKIP in locostatin function.', 'We analyzed locostatin interaction with RKIP and examined the biological consequences of locostatin binding on RKIP function. NMR studies show that a locostatin precursor binds to the conserved phosphatidylethanolamine binding pocket of RKIP. However, drug binding to the pocket does not prevent RKIP association with its inhibitory target, Raf-1, nor affect RKIP phosphorylation by Protein Kinase C at a regulatory site. Similarly, exposure of wild type, RKIP-depleted HeLa cells or RKIP-deficient (RKIP(-/-)) mouse embryonic fibroblasts (MEFs) to locostatin has no effect on MAP kinase activation. Locostatin treatment of wild type MEFs causes inhibition of cell migration following wounding. RKIP deficiency impairs migration further, indicating that RKIP protects cells against locostatin-mediated inhibition of migration. Locostatin treatment of depleted or RKIP(-/-) MEFs reveals cytoskeletal disruption and microtubule abnormalities in the spindle.",
            "output": [
                "Does raf Kinase Inhibitory Protein protect cells against locostatin-mediated inhibition of migration?"
            ]
        },
        {
            "id": "task847-8e7f9d8ecfe54a2c9f7e01023c5ae312",
            "input": "Oxidative stress is associated with atrial fibrillation (AF). However, little is known about the relationship between serum markers of oxidation and electrical activity in patients with AF.', 'The purpose of this study was to investigate the possible association between serum markers of reactive oxidative metabolism and atrial remodeling in paroxysmal and persistent AF.', 'Derivatives of reactive oxidative metabolites (DROM), an index of oxidative stress, were measured in 306 consecutive patients with AF (225 paroxysmal, 81 persistent) undergoing radiofrequency (RF) catheter ablation. Filtered P-wave duration by P-wave signal-averaged ECG and levels of high-sensitivity C-reactive protein (CRP) as an inflammatory marker also were measured.', 'Patients were followed up for 1.2 +/- 0.8 years. DROM levels in patients with persistent AF were significantly higher than in patients with paroxysmal AF (341.6 +/- 85.5 Carratelli [Carr] units vs 305.0 +/- 77.7 Carr units, P <.001). DROM levels showed a tighter, positive correlation with filtered P-wave duration in persistent AF patients (r = 0.56, P <.001) than in all AF patients (r = 0.13, P <.05). DROM levels also showed a weaker but significant correlation with high-sensitivity CRP in patients with AF. Kaplan-Meier analysis revealed that the highest quartile of basal DROM levels exhibited a significantly higher AF recurrence rate after RF catheter ablation in patients with paroxysmal AF (P <.01).",
            "output": [
                "Are reactive oxidative metabolites associated with atrial conduction disturbance in patients with atrial fibrillation?"
            ]
        },
        {
            "id": "task847-36c2859498a34f99bd45f6ed44365e13",
            "input": "The pathophysiology underlying methotrexate (MTX)-induced pneumonitis has been considered as a hypersensitive reaction. The lymphocyte transformation test (LTT) is frequently used to detect hypersensitivity. Whereas previous reports have proposed that the LTT is not ideal to detect hypersensitivity to MTX, it has not been directly confirmed.', 'Forty rheumatoid arthritis (RA) patients (24 patients currently taking MTX and 16 patients with a past history of MTX administration) and 13 healthy subjects were recruited. LTT with MTX was used to assess thymidine incorporation. An MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay was also performed. The mitogenic activity was expressed as the Stimulatory Index (SI). The activity of RA was assessed by the disease activity score 28 (DAS28).', 'In the presence of MTX, the SI measured by the LTT and by the MTS assay showed an inverse correlation. The presence of MTX significantly elevated the SI values measured by the LTT. However, the SI values were significantly lower in RA patients currently taking MTX than those of patients not currently taking MTX, although DAS28 was not different. Furthermore, a past history of MTX-induced pneumonitis did not affect the SI values.",
            "output": [
                "Is lymphocyte transformation test helpful for the diagnosis of methotrexate-induced pneumonitis in patients with rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-22d43dabf586419f829f9dc51d935f1d",
            "input": "An electro-spray ionisation ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) application for the quantitative analysis of amino acids was developed. The suitability for the detection and follow-up of patients suffering from inborn errors of metabolism (IEM) was assessed by extensive cross-validation with ion-exchange liquid chromatography (IEX-LC) with post-column ninhydrin derivatisation, participation in external quality control (ERNDIM) and analysis of samples of patients with confirmed IEM.', 'Prior to analysis plasma and urine samples were merely diluted 150-fold in mobile phase. Amino acids were detected in the multiple reaction monitoring mode (MRM) in the ESI-positive mode. The analytical results were compared with IEX-LC. External quality control scheme performance is presented.', 'Comprehensive analysis of amino acids in plasma and urine was achieved with a run-to-run time of 30min. Validation results were satisfactory and there was a very good correlation between UPLC-MS/MS and IEX-LC. Analytical results obtained in the external quality control scheme were essentially the same as those of the other participants. Patients suffering from IEM were readily identified.",
            "output": [
                "Is quantitative UPLC-MS/MS analysis of underivatised amino acids in body fluids a reliable tool for the diagnosis and follow-up of patients with inborn errors of metabolism?"
            ]
        },
        {
            "id": "task847-3e198fe014c9454a8a7bc1bf8fccab74",
            "input": "To assess whether the free radical scavenger, edaravone, could provide protection from oxidative stress and hearing loss induced by noise exposure.', 'Forty-eight guinea pigs were divided into six groups and exposure to a stationary noise at 125 dB SPL for 2 h only once. Group A: measured hearing and reactive oxygen species (ROS) level without noise exposure. Group B: intratympanic saline injection. Group C: intratympanic edaravone injection. Group D: exposed to noise for 2 h. Group E: intravenous edaravone injection after noise exposure. Group F: intratympanic edaravone injection after noise exposure. All animals of group D, E and F were measured hearing with ABR before noise exposure, immediately after noise exposure and at 2, 6, 12, 24, 48, 72 h after noise exposure, and then were decapitated for ROS measurement with electron spin resonance technology.', \"After noise exposure, the ABR threshold of group D increased immediately after acute acoustic trauma and did not get right finally, while group F came back about 10 dB SPL. The normal level of ROS in the cochlea of guinea pigs was about 21.68 (cm/g) and significantly increased after acute acoustic trauma, reaching its peak in 2h, and didn't return to normal after 72 h. Group E did not inhibit free radicals, while group F showed significant effect on inhibiting production of free radicals.",
            "output": [
                "Does [ Edaravone protect hearing from acute acoustic trauma in guinea pigs ]?"
            ]
        },
        {
            "id": "task847-743f26b6448547c7bb96e33969459d21",
            "input": "Due to increased use of imaging techniques, adrenal incidentalomas are frequently detected. The majority are non-hyperfunctioning adrenocortical tumors. We have previously shown that expression of the gene CYP17, coding for the enzyme in the cortisol pathway, correlates with cortisol release from adrenocortical tumors in vitro. The aim of this study was to compare clinical data with mRNA expression of CYP17 and CYP11B1 in adrenocortical tumors from patients with and without Cushing's syndrome and to identify adrenal tumors that may cause subclinical Cushing's syndrome.\", 'A retrospective study of 34 patients undergoing adrenalectomy due to an adrenal tumor.', 'Clinical data were collected. In the adrenal gland the mRNA expression of the genes CYP17 and CYP11B1 was studied with in situ hybridisation technique.', \"The median ratio of CYP17/CYP11B1 expression in tumors from patients with Cushing's syndrome was significantly higher than the median ratio in the non-hyperfunctioning tumors. Tumors from 2 patients with subclinical Cushing's syndrome had ratios within the upper range for non-hyperfunctioning tumors.",
            "output": [
                "Does increased ratio of mRNA expression of the genes CYP17 and CYP11B1 indicate autonomous cortisol production in adrenocortical tumors?"
            ]
        },
        {
            "id": "task847-7be2e34ed8d1451c87f7b85774fad612",
            "input": "The major immuno-modulating effects of Ganoderma lucidum include mitogenicity and activation of immune effector cells such as T cells, macrophages and natural killer cells resulting in the production of cytokines.', 'The purpose of this study was to evaluate the expression of CD40 and CD80 by G. lucidum-treated human peripheral blood mononuclear cells.', 'Monocytes were isolated and incubated at 37 C and 5% CO2 for 24 h and 48 h in the presence or absence of different concentrations of G. lucidum. Cells were then incubated with labelled monoclonal antibodies against CD14, CD40 and B7-1(CD80) molecules utilizing standard protocols, and analyzed by flow cytometry.', 'The results showed that incubation of monocytes with G. lucidum led to marked enhancement of CD40 and B7-1 expression in a dose- and time- dependent manner (p<0.001). G. lucidum was more effective in enhancing the expression of CD80 and CD40 molecules of cells obtained from females than male donors (p<0.001).",
            "output": [
                "Does ganoderma lucidum induce the expression of CD40/CD86 on peripheral blood monocytes?"
            ]
        },
        {
            "id": "task847-c09d8d0e6fdd496f853c5260c6328eb0",
            "input": "Patient portals may improve pediatric chronic disease outcomes, but few have been rigorously evaluated for usability by parents. Using scenario-based testing with think-aloud protocols, we evaluated the usability of portals for parents of children with cystic fibrosis, diabetes or arthritis. DESIGN Sixteen parents used a prototype and test data to complete 14 tasks followed by a validated satisfaction questionnaire. Three iterations of the prototype were used.', 'During the usability testing, we measured the time it took participants to complete or give up on each task. Sessions were videotaped and content-analyzed for common themes. Following testing, participants completed the Computer Usability Satisfaction Questionnaire which measured their opinions on the efficiency of the system, its ease of use, and the likeability of the system interface. A 7-point Likert scale was used, with seven indicating the highest possible satisfaction.', 'Mean task completion times ranged from 73 (+/- 61) seconds to locate a document to 431 (+/- 286) seconds to graph laboratory results. Tasks such as graphing, location of data, requesting access, and data interpretation were challenging. Satisfaction was greatest for interface pleasantness (5.9 +/- 0.7) and likeability (5.8 +/- 0.6) and lowest for error messages (2.3 +/- 1.2) and clarity of information (4.2 +/- 1.4). Overall mean satisfaction scores improved between iteration one and three.",
            "output": [
                "Does usability testing found problems for novice users of pediatric portals?"
            ]
        },
        {
            "id": "task847-1a58257c29c04bacab2a01a521239b44",
            "input": "The objective of this study was to examine the relationship of obstructive sleep apnea (OSA), body weight (BMI percentage [BMI%]), and monosymptomatic nocturnal enuresis (MNE) in children.', 'A case-control study design was used. All children were 5 to 15 years of age; case patients were recruited from a comprehensive sleep disorders center (n = 149), and control subjects were recruited from a general pediatric practice in the same catchment area (n = 139). Case patients were subject to overnight polysomnograms and grouped into apnea severity categories (minimal, mild, moderate, or severe) on the basis of respiratory disturbance index and minimum arterial oxygen saturation levels. Data for all children included age; gender; height; weight; and history of MNE, snoring, diabetes, nasal allergies, and/or enlarged tonsils. BMI% was used to group children into weight categories as suggested by the Centers for Disease Control and Prevention (underweight, normal weight, at risk for overweight, and overweight). Two age groupings were created (5-10 years and 11-15 years). Descriptive statistics provided the prevalence of OSA, weight category, and MNE among case patients and control subjects. Cross-tabulations examined the relationship of severity of OSA with weight categories and MNE, stratified by age and gender. A series of logistic regression models explored the interrelationship of the grouping variables.', 'A large majority (79.9%) of control subjects were at risk for overweight, and a large majority (80.0%) of children with MNE also had some degree of OSA. Logistic regression demonstrated that both MNE (odds ratio: 5.29) and overweight (odds ratio 4.16) were significantly associated with OSA but not with each other.",
            "output": [
                "Are nocturnal enuresis and overweight associated with obstructive sleep apnea?"
            ]
        },
        {
            "id": "task847-2576833d1a8b44c3b3ad0db4f17e4e0d",
            "input": "Liver resection is the only curative treatment offering a chance of long-term survival in patients with colorectal liver metastases (CRM). Recent data indicated that liver resection in patients with tumor progression while receiving chemotherapy was associated with poor outcome. The aim of the study was to identify risk factors for poor outcome in patients with pre-operative chemotherapy of CRM.', 'We analyzed 160 patients after liver resection for CRM with preoperative systemic. chemotherapy. Three groups of patients were identified: 44 patients (27.5%) had a tumor response, 20 (12.5%) showed stable disease, and 96 (60%) patients had tumor progression while on chemotherapy. Median follow-up was 2.4 years (range, 6 days-11.1 years). All available clinicopathologic variables possibly associated with outcome were evaluated.', 'Survival was 88%, 53%, and 37% at 1, 3, and 5 years. Noncurative resection, carcinoembryonic antigen levels >200 ng/ml, tumor grading, size of the largest tumor >5 cm, and number of metastases were associated with poor patient outcome. In the multivariate analysis, tumor free margin and tumor grading correlated with the outcome. Tumor progression while on chemotherapy had no influence on the long-term survival.",
            "output": [
                "Does nonresponse to pre-operative chemotherapy preclude long-term survival after liver resection in patients with colorectal liver metastases?"
            ]
        },
        {
            "id": "task847-d80ec1f4cc8843fca5096f3a1e3981d6",
            "input": "Palliative sedation therapy (PST) is indicated for and used to control refractory symptoms in cancer patients undergoing palliative care. We aimed to evaluate whether PST has a detrimental effect on survival in terminally ill patients.', 'This multicenter, observational, prospective, nonrandomized population-based study evaluated overall survival in two cohorts of hospice patients, one submitted to palliative sedation (A) and the other managed as per routine hospice practice (B). Cohorts were matched for age class, gender, reason for hospice admission, and Karnofsky performance status.', 'Of the 518 patients enrolled, 267 formed cohort A and 251 cohort B. In total, 25.1% of patients admitted to the participating hospices received PST. Mean and median duration of sedation was 4 (standard deviation 6.0) and 2 days (range 0-43), respectively. Median survival of arm A was 12 days [90% confidence interval (CI) 10-14], while that of arm B was 9 days (90% CI 8-10) (log rank = 0.95, P = 0.330) (unadjusted hazard ratio = 0.92, 90% CI 0.80-1.06).",
            "output": [
                "Does palliative sedation therapy hasten death : results from a prospective multicenter study?"
            ]
        },
        {
            "id": "task847-73573801f4554c7ab6b8ba5ff8686742",
            "input": "To investigate if diabetic patients without diabetic retinopathy despite long disease duration have different human leukocyte antigen (HLA) status vs those with an early onset of retinopathy.', 'Retrospective, nonrandomized, masked comparative study. Type 1 diabetic patients with a disease onset before age 30 were recruited to the study. The study population consisted of two groups of diabetic patients: those with normal retinopathy course (retinopathy developed during the first 20 years of diabetes onset) (23 patients) and those with postponed retinopathy (no obvious retinopathy in spite of passing 20 years of diabetes) (19 patients). These groups were matched with regard to level of glycemic control, blood pressure, and lipid profile. A group of 23 healthy patients served as controls. HLA-DQB1 typing of blood samples was done using a polymerase chain reaction with sequence-specific primer (PCR-SSP) method.', 'HLA-DQB1*0201/HLA-DQB1*0501 and HLA-DQB1*0201/HLA-DQB1*0504 haplotypes were more common among type 1 diabetic patients with normal retinopathy course than those with postponed retinopathy (26.1% vs 0.0%; p=0.019). HLA-DQB1*0301 and HLA-DQB1*0304 were less common among those diabetic patients with normal retinopathy course than those with a postponed retinopathy (63.2% vs 34.8%; p=0.067).",
            "output": [
                "Do hLA-DQB1 subtypes predict diabetic retinopathy in patients with type I diabetes mellitus?"
            ]
        },
        {
            "id": "task847-9032028cbc884fc9a5d7273d09d6fa1f",
            "input": "Obstructive sleep apnea (OSA) has been linked with erectile dysfunction (ED), but it is unknown whether this association is maintained in the presence of other risk factors for ED.', 'The aim of this study was to evaluate the relationship between ED/sexual dysfunction and polysomnographic measures of sleep apnea in patients with known risk factors for ED.', 'Prospective cross-sectional analysis of 401 male patients undergoing in-lab polysomnography for suspected OSA. Erectile (EF) and sexual function were assessed by the 15-item International Index of Erectile Function (IIEF-15) questionnaire.', 'Severity of OSA via apnea-hypopnea index (AHI) and mean/lowest nocturnal oxygen saturation (SaO(2)). The IIEF-15 including the sexual domains: EF, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction.', 'OSA (AHI > 5/h) was diagnosed in 92% of patients. ED (EF subdomain < or = 25) was present in 69% of patients with, and 34% of patients without OSA (P < 0.001). Multivariate stepwise regression analyses including known risk factors for ED, such as age, obesity, coronary heart disease, peripheral occlusive disease, hypertension, diabetes, prostate surgery, and beta-blocker treatment, and measures of sleep apnea identified mean nocturnal SaO(2) as independently associated with ED (P = 0.002; mean [95% CI] normalized slope 0.126 [0.047; 0.205]). Age (P < 0.001), peripheral occlusive disease (P = 0.001), prostate surgery (P = 0.018), and hypertension (P = 0.021) were confirmed as risk factors for ED, but did not abolish the sleep apnea-associated risk. Similar results were obtained for sexual dysfunction. Logistic regression analysis using the diagnosis of ED (EF subdomain < or = 25) as binary dependent variable confirmed that mean nocturnal SaO(2) (P = 0.012), as well as age (P < 0.001) were independently associated with ED.",
            "output": [
                "Is sleep apnea an independent correlate of erectile and sexual dysfunction?"
            ]
        },
        {
            "id": "task847-60317b957b374f9fb653b80d338a3f79",
            "input": "To evaluate the relationship between retinal vascular occlusions (RVOs) and exfoliation syndrome (XFS) in a cohort of patients with the two conditions.', 'We reviewed the records of patients with XFS with or without glaucoma and any type of RVO between 1983 and 2007. Patients with prior incisional surgery or a history of uveitis were excluded. Data collected included demographics, systemic comorbidities, type of RVO, and intraocular pressure (IOP) before the RVO. Slit-lamp biomicroscopy regarding the presence of exfoliation material on the lens capsule and pupillary margin before the vascular event was used to evaluate the laterality and degree of XFS.', 'We identified 36 patients (mean age 78.4+/-8.3 years, 19 women). Most patients were of European descent (34/36) and 20 (56%) had no prior glaucoma diagnosis. The most common retinal vascular events were central retinal vein occlusion (18/36) and BRVO (10/36). Mean IOP between eyes with (19.5+/-6.5 mm Hg) and without (17.9+/-4.8 mm Hg) RVO was similar (P=0.12). RVOs occurred more commonly in the eye with more pronounced XFS in 92% (33/36) of the cases. A similar agreement was found when considering patients with and without glaucoma separately (94% (15/16) vs90% (18/20); P=0.83). In addition, no difference in the agreement percentage was observed when comparing patients with unilateral XFS (87% (13/15)) with all study patients (P=0.87).",
            "output": [
                "Do retinal vascular occlusions occur more frequently in the more affected eye in exfoliation syndrome?"
            ]
        },
        {
            "id": "task847-c4688be896ee4c02bcede725316d3dd1",
            "input": "Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role.', 'Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (primary outcome) and reduce S-100B and free radical formation (secondary outcome).', 'In a randomized, double-blind feasibility study, 53 pregnant women in labor (54 fetuses) with a gestational age of >36 weeks and fetal hypoxia, as indicated by abnormal/nonreassuring fetal heart rate tracing or fetal scalp pH of <7.20, received 500 mg of allopurinol or placebo intravenously. Severity of fetal hypoxia, brain damage and free radical formation were assessed by arterial cord blood lactate, S-100B and non-protein-bound-iron concentrations, respectively. At birth, maternal and cord blood concentrations of allopurinol and its active metabolite oxypurinol were determined.', 'Allopurinol and oxypurinol concentrations were within the therapeutic range in the mother (allopurinol > 2 mg/L and/or oxypurinol > 4 mg/L) but not always in arterial cord blood. We therefore created 3 groups: a placebo (n = 27), therapeutic allopurinol (n = 15), and subtherapeutic allopurinol group (n = 12). Cord lactate concentration did not differ, but S-100B was significantly lower in the therapeutic allopurinol group compared with the placebo and subtherapeutic allopurinol groups (P < .01). Fewer therapeutic allopurinol cord samples had measurable non-protein-bound iron concentrations compared with placebo (P < .01).",
            "output": [
                "Does maternal allopurinol during fetal hypoxia lower cord blood levels of the brain injury marker S-100B?"
            ]
        },
        {
            "id": "task847-1bcb65751e0549faac6cb913c6afc541",
            "input": "Cerebral pressure passivity is common in sick premature infants and may predispose to germinal matrix/intraventricular hemorrhage (GM/IVH), a lesion with potentially serious consequences. We studied the association between the magnitude of cerebral pressure passivity and GM/IVH.', \"We enrolled infants <32 weeks' gestational age with indwelling mean arterial pressure (MAP) monitoring and excluded infants with known congenital syndromes or antenatal brain injury. We recorded continuous MAP and cerebral near-infrared spectroscopy hemoglobin difference (HbD) signals at 2 Hz for up to 12 hours/day and up to 5 days. Coherence and transfer function analysis between MAP and HbD signals was performed in 3 frequency bands (0.05-0.25, 0.25-0.5, and 0.5-1.0 Hz). Using MAP-HbD gain and clinical variables (including chorioamnionitis, Apgar scores, gestational age, birth weight, neonatal sepsis, and Score for Neonatal Acute Physiology II), we built a logistic regression model that best predicts cranial ultrasound abnormalities.\", 'In 88 infants (median gestational age: 26 weeks [range 23-30 weeks]), early cranial ultrasound showed GM/IVH in 31 (37%) and parenchymal echodensities in 10 (12%) infants; late cranial ultrasound showed parenchymal abnormalities in 19 (30%) infants. Low-frequency MAP-HbD gain (highest quartile mean) was significantly associated with early GM/IVH but not other ultrasound findings. The most parsimonious model associated with early GM/IVH included only gestational age and MAP-HbD gain.",
            "output": [
                "Is elevated cerebral pressure passivity associated with prematurity-related intracranial hemorrhage?"
            ]
        },
        {
            "id": "task847-569a85f79e8741e792a610e05764588f",
            "input": "With male gender as a strong predictor of cardiovascular instability, we hypothesized that gender-specific differences in circulating carbon monoxide levels contributed to dysregulated microvascular function in preterm male infants.', 'Infants born at 24 to 34 weeks of gestation (N = 84) were studied in a regional tertiary neonatal unit. Carboxyhemoglobin levels were measured through spectrophotometry in umbilical arterial blood and at 24, 72, and 120 hours after birth. Microvascular blood flow was determined through laser Doppler flowmetry.', 'Carboxyhemoglobin levels demonstrated a strong inverse relationship with gestational age (r = -0.636; P < .001) and were higher in boys (P = .032). Repeated-measures analysis of variance showed a significant decrease in arterial carboxyhemoglobin levels over time (P < .001), with significant between-subjects effects for gestational age (P = .011) and gender (P = .025). Positive correlations with microvascular blood flow at 24 hours of age (r = 0.495; P < .001) and 120 hours of age (r = 0.548; P < .001) were observed. With controlling for gestational age, carboxyhemoglobin levels at 72 hours were greater for infants who died in the first week of life (P = .035).",
            "output": [
                "Is carbon monoxide a significant mediator of cardiovascular status following preterm birth?"
            ]
        },
        {
            "id": "task847-009bb74b6a6f4815a744993300afaf64",
            "input": "Mild hypothermia for 72 hours is neuroprotective in newborns with moderate or severe hypoxic-ischemic encephalopathy. A core temperature of 33.5 degrees C might reduce drug clearance leading to potential toxicity. Gentamicin is nephrotoxic and ototoxic at high serum concentrations. No study has investigated the influence of 72 hours of hypothermia on serum gentamicin concentrations (SGCs) in children of any age. We aimed to compare the SGCs in encephalopathic infants who underwent intensive care with therapeutic hypothermia or normothermia.', 'Data were collected retrospectively from 2 NICUs in Bristol, United Kingdom, that offered cooling therapy within clinical trials since 1998. Eligible infants (n = 55) developed grade 2/3 encephalopathy after birth and fulfilled the entry criteria defined in the CoolCap trial. Encephalopathic infants with similar demographic values were either nursed under normothermia or 72 h-hypothermia. Once-daily gentamicin dosage (4-5 mg/kg) was administered, and trough SGC was recorded with corresponding creatinine concentrations. The time and number of omitted drug doses were noted.', 'Mean trough SGC (pre-second dose) and mean plasma creatinine concentrations for both treatment groups were similar (gentamicin: 2.19 +/- 1.7 [hypothermia] and 2.30 +/- 2.0 [normothermia] mg/L; creatinine: 115.6 +/- 42.8 [hypothermia] and 121.0 +/- 45.1 [normothermia] mumol/L). Forty percent of the trough SGCs in both groups were above the recommended trough concentration of 2.0 mg/L. A significant correlation (r(2) = 0.36) was found between high SGCs and impaired renal function assessed by raised plasma creatinine levels regardless of treatment options.",
            "output": [
                "Are serum gentamicin concentrations in encephalopathic infants affected by therapeutic hypothermia?"
            ]
        },
        {
            "id": "task847-68e5ef18f86b4a11a22d584e54129ee0",
            "input": "To summarise the present evidence for an association between circulating fibrinogen or D-dimer and presence of abdominal aortic aneurysm (AAA) presence.', 'MEDLINE database was searched to identify all case-control studies that compared plasma fibrinogen or D-dimer concentrations between patients with AAA and subjects without AAA. For each study, data regarding fibrinogen or D-dimer concentrations in both the AAA and control groups were used to generate mean differences (MDs) and 95% confidence intervals (CIs). Study-specific estimates were combined using inverse variance-weighted average of logarithmic MDs in both fixed- and random-effects models.', 'Our search identified 10 eligible studies including 834 cases with AAA and 6971 controls without AAA for fibrinogen and six studies including 264 patients with AAA and 403 subjects without AAA for D-dimer. Pooled analysis demonstrated significantly higher fibrinogen (fixed-effects MD, 0.37gl(-1); 95% CI: 0.30-0.44gl(-1)) and D-dimer (random-effects MD: 415.36ngml(-1); 95% CI: 128.97-701.76ngml(-1)) concentrations in the AAA group than those in the control group.",
            "output": [
                "Are plasma fibrinogen and D-dimer concentrations associated with the presence of abdominal aortic aneurysm : a systematic review and meta-analysis?"
            ]
        },
        {
            "id": "task847-282e0bc6d25543c99ab5c0a78f412549",
            "input": "Several Northern Hemisphere Drosera species have been used in the therapy of respiratory tract infections as the traditional medicine Droserae Herba.', 'To determine the anti-inflammatory effects of Drosera species and to investigate a substitute material for Droserae Herba, we examined the effect of extracts of Drosera rotundifolia, Drosera tokaiensis and Drosera spatulata on activated T cell membrane (aTc-m)-induced inflammatory gene expression in HMC-1 human mast cells.', 'Drosera rotundifolia, Drosera spatulata and Drosera tokaiensis were collected in Japan. Herbs were extracted with 80% EtOH, and subsequently applied to OASIS HLB column. HMC-1 cells were treated with each Drosera column-adsorbed fraction for 15min, and subsequently added to aTc-m and incubated for 16h. Inflammatory gene and protein expressions were determined by DNA microarray, RT-PCR and Western blotting.', 'Drosera rotundifolia and Drosera tokaiensis fractions, but not the Drosera spatulata fraction, suppressed inflammatory gene expression induced by aTc-m in HMC-1 cells.",
            "output": [
                "Do drosera rotundifolia and Drosera tokaiensis suppress the activation of HMC-1 human mast cells?"
            ]
        },
        {
            "id": "task847-83be086835e54a808337759e9f6c017d",
            "input": "We previously showed that the cardioversion threshold (CVT) for ventricular tachycardia (VT) is phase dependent when a single monophasic shock (1MP) is used.', 'The purpose of this study was to extend these findings to a biphasic shock (1BP) and to compare the efficacy of phase-independent multiple monophasic (5MP) and biphasic shocks (5BP).', 'Panoramic optical mapping with blebbistatin (5 microM) was performed in postmyocardial infarction rabbit hearts (n = 8). Flecainide (1.64 +/- 0.68 microM) was administered to promote sustained arrhythmias. 5MP and 5BP were applied within one VT cycle length (CL). Results were compared to 1BP and antitachycardia pacing.', 'We observed monomorphic VT with CL = 149.6 +/- 18.0 ms. Similar to 1MP, CVTs of 1BP were found to be phase dependent, and the maximum versus minimum CVT was 8.6 +/- 1.7 V/cm versus 3.7 +/- 1.9 V/cm, respectively (P = .0013). Efficacy of 5MP was higher than that of 1BP and 5BP. CVT was 3.2 +/- 1.4 V/cm for 5MP versus 5.3 +/- 1.9 V/cm for 5BP (P = .00027). 5MP versus averaged 1BP CVT was 3.6 +/- 2.1 V/cm versus. 6.8 +/- 1.5 V/cm, respectively (P = .00024). Antitachycardia pacing was found to be completely ineffective in this model.",
            "output": [
                "Do multiple monophasic shocks improve electrotherapy of ventricular tachycardia in a rabbit model of chronic infarction?"
            ]
        },
        {
            "id": "task847-d94ad46121ca4598bfaec850a173769c",
            "input": "Transmural heterogeneity in ventricular repolarization demonstrated in vitro has been difficult to confirm in vivo. Whether this discrepancy reflects a physiological phenomenon or a methodological problem remains a vivid matter of debate despite a plethora of experimental work. Therefore, we have measured the relevant electrophysiological parameters first in vivo and repeated these in the same heart and at identical sites in vitro. Methodological issues were tackled by using both unipolar and bipolar recordings. Physiological issues were explored by measuring both local and functional electrophysiological parameters.', 'In 10 healthy dogs, 2 high-resolution needle electrodes were inserted into the left ventricle. Effective refractory periods (ERP) as well as activation recovery intervals (ARI) were determined at each electrode along both needles at basic cycle lengths (BCL) of 850 and 300 ms, respectively. After excision of the heart, ERP and ARI measurements were repeated in the arterially perfused wedge preparations.', 'First, we observed that ERPs and ARIs were significantly shorter in vivo than in vitro. Mean ERPs and ARIs of all muscle layers were relatively uniform throughout the ventricular wall in vivo. The transition from the in vivo to the in vitro preparation was associated with a significant albeit small increase of mean ARIs in the subendocardium, whereas interlayer differences in mean ERPs did not reach statistical significance as in vivo.",
            "output": [
                "Is there no transmural heterogeneity in an index of action potential duration in the canine left ventricle?"
            ]
        },
        {
            "id": "task847-d9a3624062304631b9d2cc747de02063",
            "input": "We evaluated whether CK19, one of the main cytoskeleton proteins of epithelial cells, is released as full-length protein from viable tumor cells and whether this property is relevant for metastatic progression in breast cancer patients.', 'EPISPOT (EPithelial ImmunoSPOT) assays were performed to analyze the release of full-length CK19 by carcinoma cells of various origins, and the sequence of CK19 was analyzed with mass spectrometry. Additional functional experiments with cycloheximide, Brefeldin A, or vincristine were done to analyze the biology of the CK19-release. CK19-EPISPOT was used to detect disseminated tumor cells in bone marrow (BM) of 45 breast cancer patients who were then followed up over a median of 6 years.', 'CK19 was expressed and released by colorectal (HT-29, HCT116, Caco-2) and breast (MCF-7, SKBR3, and MDA-MB-231) cancer cell lines. The CK19-EPISPOT was more sensitive than the CK19-ELISA. Dual fluorescent EPISPOT with antibodies against different CK19 epitopes showed the release of the full-length CK19, which was confirmed by mass spectrometry. Functional experiments indicated that CK19 release was an active process and not simply the consequence of cell death. CK19-releasing cells (RCs) were detectable in BM of 44% to 70% of breast cancer patients. This incidence and the number of CK19-RCs were correlated to the presence of overt metastases, and patients with CK19-RCs had a reduced survival as compared with patients without these cells (P = 0.025, log-rank test; P = 0.0019, hazard ratio, 4.7; multivariate analysis).",
            "output": [
                "Is full-length cytokeratin-19 released by human tumor cells : a potential role in metastatic progression of breast cancer?"
            ]
        },
        {
            "id": "task847-78efcbaea042487085adc13e211a8ea0",
            "input": "Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue.', 'Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways.",
            "output": [
                "Does dietary carbohydrate modification alter serum metabolic profiles in individuals with the metabolic syndrome?"
            ]
        },
        {
            "id": "task847-5c372b7defcd4048af4622a482914c65",
            "input": "To elucidate the detailed mechanisms underlying the appreciable effects of JG3, a novel marine-derived oligosaccharide, on cell migration using a Chinese hamster ovary (CHO) cell line stably over-expressing heparanase.', 'A retrovirus infection system was used to establish a CHO-K1 cell line stably transfected with heparanase. Immunocytochemistry was used to assess cell morphology. Flow cytometry was selected to analyze the activation of beta1-integrin, and Western blotting was used to analyze the downstream effects on the cell adhesion pathway. An affinity precipitation assay was used to determine activation of the small GTPases, Rac1, and RhoA.', 'JG3 abolished heparanase-driven formation of focal adhesions and cell spreading. Although JG3 failed to block the heparanase-triggered activation of beta1-integrin or the phosphorylation of Src, the oligosaccharide caused a significant dephosphorylation of FAK and subsequent inactivation of Erk. Furthermore, JG3 was found to arrest the activation of Rac1.",
            "output": [
                "Does marine-derived oligosaccharide sulfate ( JG3 ) suppress heparanase-driven cell adhesion events in heparanase over-expressing CHO-K1 cells?"
            ]
        },
        {
            "id": "task847-7564e4b17c064c43b4a4306fe2c3ae1b",
            "input": "It has been suggested that anti-citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). To exert their pathologic effects, ACPAs must recruit immune effector mechanisms such as activation of the complement system. Mouse models of RA have shown that, surprisingly, arthritogenic antibodies activate the alternative pathway of complement rather than the expected classical pathway. This study was undertaken to investigate whether human anti-cyclic citrullinated peptide (anti-CCP) antibodies activate the complement system in vitro and, if so, which pathways of complement activation are used.', 'We set up novel assays to analyze complement activation by anti-CCP antibodies, using cyclic citrullinated peptide-coated plates, specific buffers, and normal and complement-deficient sera as a source of complement.', 'Anti-CCP antibodies activated complement in a dose-dependent manner via the classical pathway of complement, and, surprisingly, via the alternative pathway of complement. The lectin pathway was not activated by anti-CCP antibodies. Complement activation proceeded in vitro up to the formation of the membrane attack complex, indicating that all activation steps, including the release of C5a, took place.",
            "output": [
                "Do anti-cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathways?"
            ]
        },
        {
            "id": "task847-10cfee0acd3e4b1f96e04da80da94d55",
            "input": "Endogenous glucocorticoids (GCs) modulate numerous biologic systems involved in the initiation and maintenance of arthritis. Bone cells play a critical role in the progression of arthritis, and some of the effects of GCs on inflammation may be mediated via these cells. The aim of this study was to investigate the impact of osteoblast-targeted disruption of GC signaling on joint inflammation, cartilage damage, and bone metabolism in the K/BxN mouse serum transfer model of autoimmune arthritis.', 'Intracellular GC signaling was disrupted in osteoblasts through transgenic overexpression of 11beta-hydroxysteroid dehydrogenase type 2 under the control of a type I collagen promoter. Arthritis was induced in 5-week-old male transgenic mice and their wild-type (WT) littermates, and paw swelling was assessed daily until the mice were killed. The mice were examined by histology, histomorphometry, and microfocal computed tomography, and serum was analyzed for cytokines, adrenocorticotropic hormone, and corticosterone.', 'Acute arthritis developed in both transgenic and WT mice treated with K/BxN mouse serum. However, the arthritis and local inflammatory activity were significantly attenuated in transgenic mice, as judged by clinical and histologic indices of inflammation and cartilage damage. Bone turnover and bone volume remained unchanged in arthritic transgenic mice, while WT mice exhibited stimulated bone resorption, suppressed osteoblast activity, and significantly reduced bone volume, compatible with the known effects of active inflammation on bone. Circulating levels of proinflammatory cytokines tended to be lower in arthritic transgenic mice than in control transgenic mice.",
            "output": [
                "Does transgenic disruption of glucocorticoid signaling in mature osteoblasts and osteocytes attenuate K/BxN mouse serum-induced arthritis in vivo?"
            ]
        },
        {
            "id": "task847-fceb4a6f11174e98bc954b780ad426da",
            "input": "Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors.', 'Cases were 445 children with JIA, and controls were 643 healthy adults. Using the TaqMan assay, subjects were genotyped for 8 single-nucleotide polymorphisms in 7 loci including rs10499194 and rs6920220 in the TNFAIP3 locus, rs6679677 in the RSBN1 locus, rs17696736 in the C12orf30 locus, rs3761847 in the TRAF1/C5 locus, rs2104286 in the IL2RA locus, rs7574865 in the STAT4 locus, and rs2542151 in the PTPN2 locus. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.', 'The strongest associations with JIA risk or protection were observed for TNFAIP3 variants rs10499194 (OR 0.74 [95% CI 0.61-0.91], P < 0.004) and rs6920220 (OR 1.30 [95% CI 1.05-1.61], P = 0.015). We also observed associations between JIA and both STAT4 (OR 1.24 [95% CI 1.02-1.51], P = 0.029) and C12orf30 (OR 1.20 [95% CI 1.01-1.43], P = 0.041) variants. The PTPN2 variant rs2542151 deviated from Hardy-Weinberg equilibrium and was excluded from analyses. Variants in IL2RA, TRAF1/C5, and RSBN1 were not associated with JIA. After stratification by JIA subtype, the TNFAIP3 and C12orf30 variants were associated with oligoarticular JIA, while the STAT4 variant was associated primarily with polyarticular JIA.",
            "output": [
                "Are variants in TNFAIP3 , STAT4 , and C12orf30 loci associated with multiple autoimmune diseases also associated with juvenile idiopathic arthritis?"
            ]
        },
        {
            "id": "task847-facf60f679f844a7a8363679e1c62cd2",
            "input": "The peritoneal equilibration test (PET) was developed some 25 yr ago and has been used to help prescribe peritoneal dialysis. However, PET is affected by several factors, including diabetes and inflammation. It was speculated that extracellular fluid overload would increase PET ultrafiltration volumes, and therefore the usefulness of the PET in routine clinical practice was audited.', 'Data from 211 consecutive patients attending a university teaching hospital for a standard PET who had multifrequency bioimpedance performance were analyzed to determine which factors affected net PET ultrafiltration volumes.', 'Net PET ultrafiltration volume was independent of gender, age, diabetes, residual renal function, peritoneal dialysis prescriptions (modes and dialysates), extracellular fluid volume, or C-reactive protein (CRP). There was an inverse regression with serum albumin and sodium on multiple logistical regression analysis (F = 13.4, P < 0.001 and F = 10.1, P = 0.001, respectively) and a positive regression with 24-h net peritoneal ultrafiltration volumes (F = 15.5, P < 0.001). As expected, there was a strong correlation with net sodium losses (r = 0.99, P < 0001).",
            "output": [
                "Does hydration status influence peritoneal equilibration test ultrafiltration volumes?"
            ]
        },
        {
            "id": "task847-70ae13f034244cd89a04281b5b4145e7",
            "input": "The zebrafish Danio rerio is an excellent model system for mammalian gastrointestinal development. To identify differentially regulated genes important in gastrointestinal organogenesis, we profiled the transcriptome of the zebrafish developing gastrointestinal tract.', 'Embryos from a transgenic zebrafish line expressing green fluorescent protein (GFP) in the developing intestine, liver, and pancreas were dissociated at 4 developmental time points, their cells sorted based on GFP expression with fluorescence-activated cell sorting (FACS), and analyzed with microarrays. To improve our analysis, we annotated the Affymetrix Zebrafish GeneChip with human orthologs.', 'Transcriptional profiling showed significant differences between GFP(+) and GFP(-) cells. Up-regulated genes and pathways were consistent with mammalian gastrointestinal development, such as hepatic nuclear factor gene networks and cancer. We implicate the phosphatidylinositol 3 kinase (PI3K) pathway and show that inhibition with LY294002 causes gastrointestinal defects in zebrafish. We identified novel genes, such as the microRNAs miR-217 and miR-122, the tight junction protein claudin c, the gene fam136a, and a zebrafish tetraspanin. Novel pathways include genes containing a putative transcription factor binding sequence, GGAANCGGAANY, and a nucleolar gene network. The zebrafish microarrays also identify a set of 32 genes that may mediate the effects of gain of chromosome arm 8q in human colon, liver, and pancreatic cancers.",
            "output": [
                "Does fACS-assisted microarray profiling implicate novel genes and pathways in zebrafish gastrointestinal tract development?"
            ]
        },
        {
            "id": "task847-c930afa8b69444f59bdc71ee7cbeed5c",
            "input": "S-phase cells are more resistant to low-linear energy transfer (LET) ionizing radiation (IR) than nonsynchronized and G(1)-phase cells, because both nonhomologous end-joining (NHEJ) and homologous recombination repair can repair DNA double-strand breaks (DSBs) in the S phase. Although it was reported 3 decades ago that S-phase cells did not show more resistance to high-LET IR than cells in other phases, the mechanism remains unclear. We therefore attempted to study the phenotypes and elucidate the mechanism involved.', 'Wild-type and NHEJ-deficient cell lines were synchronized using the double-thymidine approach. A clonogenic assay was used to detect the sensitivity of nonsynchronized, synchronized S-phase, and G(2)-phase cells to high- and low-LET IR. The amounts of Ku bound to DSBs in the high- and low-LET-irradiated cells were also examined.', 'S-phase wild-type cells (but not NHEJ-deficient cells) were more sensitive to high-LET IR than nonsynchronized and G(2)-phase cells. In addition, S-phase wild-type cells showed less efficient Ku protein binding to DSBs than nonsynchronized and G(2)-phase cells in response to high-LET IR, although all cells at all phases showed similarly efficient levels of Ku protein binding to DSBs in response to low-LET IR.",
            "output": [
                "Are s-phase cells more sensitive to high-linear energy transfer radiation?"
            ]
        },
        {
            "id": "task847-f4307d94010c4d4a812a8d34cf6a1a58",
            "input": "Severe generalized spastic movement disorders of various aetiologies often involve the jaw muscles and lead to a spastic trismus with masseter muscle hypertonia. We report a placebo-controlled randomized study on patients with spastic trismus.', 'Eleven patients with masseter hypertonia because of stroke, hypoxic encephalopathy or traumatic brain injury were allocated to either botulinum toxin serotype B (BoNT/B) injections into the masseter muscles or placebo treatment. The dental gap, the amount of saliva, salivation scales, and a clinical goal attainment were evaluated.', 'Three weeks after injection the BoNT/B group showed a significantly increased mouth opening compared with placebo treatment (P < 0.05). In addition to the muscle paralysing effect, a goal attainment scale demonstrated a clinical benefit for the BoNT/B group (P < 0.01).",
            "output": [
                "Does botulinum toxin B increase mouth opening in patients with spastic trismus?"
            ]
        },
        {
            "id": "task847-f82420b356a64925870ed67c14de13ce",
            "input": "Insulin resistance and hyperglycaemia are common in severe sepsis. Mitochondrial uncoupling protein 2 (UCP2) plays a role in insulin release and sensitivity.', 'To determine if a common, functional polymorphism in the UCP2 gene promoter region (the -866 G/A polymorphism) contributes to the risk of hyperglycaemia in severe sepsis.', 'In the prospective group 120 non-diabetic patients who were carriers of the G allele had significantly higher maximum blood glucose recordings than non-carriers (mean (SD) AA 8.5 (2.2) mmol/l; GA 8.5 (2.4) mmol/l; GG 10.1 (3.1) mmol/l; p = 0.0042) and required significantly more insulin to maintain target blood glucose (p = 0.0007). In the retrospective study 103 non-diabetic patients showed a similar relationship between maximum glucose and UCP genotype (AA 6.8 (2.3) mmol/l; GA 7.8 (2.2) mmol/l; GG 9.2 (2.9) mmol/l; p = 0.0078).",
            "output": [
                "Does a common UCP2 polymorphism predispose to stress hyperglycaemia in severe sepsis?"
            ]
        },
        {
            "id": "task847-49b4e72e32eb484ebe24ce4edb439e3a",
            "input": "Venous grafts are commonly used to treat drug-resistant coronary artery disease, although long-term functionality is limited because of proliferation and migration of smooth muscle cells (SMC). As proliferating SMC are particularly susceptible for the stimulating effects of cytomegalovirus (CMV), we hypothesized that CMV infection may enhance cell proliferation and graft failure. Furthermore, we evaluated the potential of FK778 to prevent intimal hyperplasia. Apart from its antiviral properties, FK778 is a new immunosuppressive agent which may also affect SMC proliferation, making it an interesting drug to prevent (CMV-enhanced) venous graft intimal hyperplasia.', 'Epigastric vein-to-common femoral artery interposition grafts were placed in four groups of 10 rats each. Rats received either FK778 (oral treatment, 15 mg/kg), were infected with CMV (1.25 x 10(6) plaque-forming units) or were both treated and infected.', 'CMV infection resulted in a significant increase in intimal and medial cross-sectional area and medial wall thickness of the vein grafts. This effect was diminished by administration of FK778. Moreover, FK778 treatment alone resulted in a significant decrease in neointimal area and percentage of stenosis versus the control group.",
            "output": [
                "Does fK778 attenuate cytomegalovirus-enhanced vein graft intimal hyperplasia in a rat model?"
            ]
        },
        {
            "id": "task847-b96c3d68f45e4a948d8d762cbfa3647b",
            "input": "Cardiopulmonary resuscitation (CPR) is now widely used as a treatment for ventricular fibrillation, though numerous studies have shown the outcome of standard CPR to be dismal. Alternative methods of CPR, including interposed abdominal compression, constant aortic occlusion, and the use of intrathoracic pressure regulator, have been shown to increase cardiac output and affect the mortality rate of CPR.', 'Here we suggest the Trendelenburg position as yet another method of increasing cardiac output and therefore improving the effectiveness of chest compressions. We hypothesized that the use of the Trendelenburg position during CPR would increase cardiac output as measured by carotid blood flow.', 'We anaesthetized six pigs and measured their pre-arrest carotid flow rate for two minutes. We then induced ventricular fibrillation in those pigs and performed open-chest CPR on them. Post-arrest carotid blood flow was measured for two minutes each at 0 (supine position), 10, 20, and 30 degrees of head-down tilt in each pig. The mean carotid flow for each degree of tilt was compared to mean carotid flow at 0 degrees of tilt using a paired student t-test.', 'We found an increase of up to 1.4-fold in carotid blood flow during CPR in the Trendelenburg position, though only 20 and 30 degrees of Trendelenburg showed a statistically significant increase from the 0 degrees of tilt in pigs.",
            "output": [
                "Does use of the trendelenburg position in the porcine model improve carotid flow during cardiopulmonary resuscitation?"
            ]
        },
        {
            "id": "task847-a4d2fca343b54518b14edf76ec11c825",
            "input": "Regulated secretion of specialized neuropeptides in the vertebrate neuroendocrine system is critical for ensuring physiological homeostasis. Expression of these cell-specific peptide markers in the differentiating hypothalamus commences prior to birth, often predating the physiological demand for secreted neuropeptides. The conserved function and spatial expression of hypothalamic peptides in vertebrates prompted us to search for critical neuroendocrine genes in newly hatched zebrafish larvae.', 'We screened mutant 5 days post-fertilization zebrafish larvae that fail to undergo visually mediated background adaptation for disruption in hypothalamic pomc expression. To our surprise, the ATPase N-ethylmaleimide sensitive factor (nsf) was identified as an essential gene for maintenance of neuroendocrine transcriptional programs during the embryo-to-larva transition. Despite normal hypothalamic development in nsf(st53) mutants, neuropeptidergic cells exhibited a dramatic loss of cell-specific markers by 5 days post-fertilization that is accompanied by elevated intracellular neuropeptide protein. Consistent with the role of NSF in vesicle-membrane fusion events and intracellular trafficking, cytoplasmic endoplasmic reticulum-like membranes accumulate in nsf(-/-) hypothalamic neurons similar to that observed for SEC18 (nsf ortholog) yeast mutants. Our data support a model in which unspent neuropeptide cargo feedbacks to extinguish transcription in neuropeptidergic cells just as they become functionally required. In support of this model we found that gnrh3 transcripts remained unchanged in pre-migratory, non-functional gonadotropin-releasing hormone (GnRH) neurons in nsf(-/-) zebrafish. Furthermore, oxytocin-like (oxtl, intp) transcripts, which are found in osmoreceptive neurons and persist in mutant zebrafish, drop precipitously after mutant zebrafish are acutely challenged with high salt.",
            "output": [
                "Do neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish?"
            ]
        },
        {
            "id": "task847-11140504387f44f9bc37b3f69ede2b29",
            "input": "The microbial etiology of periradicular lesions is recognized; however, the bacterial profile of these lesions is not well elucidated. The purpose of this study was to determine the frequency of bacterial colonization in these lesions and to characterize the bacterial community present in root ends and periradicular lesions.', 'Thirty-four adult patients who presented for apicoectomy of persistent periradicular lesions after endodontic therapy were selected for the study and samples of periradicular tissue and resected root ends collected. Total bacterial levels were estimated for 34 paired periradicular lesions and root ends using real-time polymerase chain reaction with universal bacterial primers. Sixteen pairs of these samples were analyzed using ribosomal 16S cloning and sequencing for bacterial identification.', 'Bacteria were detected more consistently and at higher levels in root ends. Periradicular lesions exhibited a diverse microbial profile with many uncultivated phylotypes. Enterococcus faecalis and Burkholderia cepacia predominated in both samples. Campylobacter gracilis and Streptococcus gordonii were associated with root ends, whereas Atopobium rimae, Peptostreptococcus micros, Streptococcus genomospecies C8, Dialister sp E2_20 E1, and Eubacterium strain A35MT were associated with periradicular lesions.",
            "output": [
                "Does molecular analysis of persistent periradicular lesions and root end reveals a diverse microbial profile?"
            ]
        },
        {
            "id": "task847-9e1e14182f5648a98becd18e3b2ae5f8",
            "input": "Consumption of vegetables and fruits, physical activity, obesity and caloric intake are all strongly related to the risk of colorectal cancer (CRC). The association between dietary intake of carotenoids from vegetables/fruits and risk of CRC in the context of cigarette smoking was studied in a nutritionally diverse population.', 'The study included 1,817 age sex residence-matched case-control pairs from a population-based study in Northern Israel. Data were acquired by food-frequency questionnaire. Individual intake of carotenoid isomers was calculated using an Israeli food content database. Odds ratios (ORs) were calculated using conditional logistic regression models adjusted for known risk factors.', 'Strong inverse associations were found with consumption of 9-cis-beta-carotene (OR = 0.35, 0.26-0.47), all-trans-beta-carotene (OR = 0.58, 0.44-0.76), cis-beta-cryptoxanthin (OR = 0.67, 0.50-0.90), all-trans-zeaxanthin (OR = 0.64, 0.48-0.86), and lutein (OR = 0.74, 0.57-0.96). Lycopene (OR = 2.22, 1.71-2.89) and all-trans-beta-cryptoxanthin (OR = 2.01, 1.48-2.73) were associated with increased risk of CRC. Inverse associations of most carotenoids with CRC, demonstrated in non-smokers, were much attenuated or reversed in past or current smokers with a highly significant interaction term.",
            "output": [
                "Does smoking attenuate the negative association between carotenoids consumption and colorectal cancer risk?"
            ]
        },
        {
            "id": "task847-4f65dc5305f54ba1bb8b72f5963fb1a4",
            "input": "There is a great need for identification of biomarkers that could improve the prediction of early osteoarthritis (OA). We undertook this study to determine whether circulating levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and C-reactive protein (CRP) can serve as useful markers of radiographic knee OA (RKOA) in a normal human population.', 'RKOA data were obtained from the cohort of the Chingford Study, a prospective population-based study of healthy, middle-aged British women. The RKOA-affected status of the subjects was assessed using the Kellgren/Lawrence (K/L) grade as determined on radiographs obtained at baseline (n = 908) and at 10 years and 15 years thereafter. Serum levels of CRP, IL-6, and TNFalpha were assayed at 5, 8, and 15 years, using high-sensitivity commercial assays. A K/L grade of >or=2 in either knee was used as the outcome measure. Statistical analyses included analysis of variance for repeated measurements and logistic regression models, together with longitudinal modeling of dichotomous responses.', 'During 15 years of followup, the prevalence of RKOA (K/L grade >or=2) increased from 14.7% to 48.7% (P < 0.00001 versus baseline). The body mass index (BMI) and circulating levels of CRP and IL-6 were consistently and significantly higher in subjects diagnosed as having RKOA. When multiple logistic regression was applied to the data, the variables of older age (P = 3.93 x 10(-5)), higher BMI at baseline (P = 0.0003), and increased levels of IL-6 at year 5 (P = 0.0129) were determined to be independent predictors of the appearance of RKOA at year 10. The results were fully confirmed using longitudinal modeling of repeated measurements of the data obtained at 3 visits. The odds ratio for RKOA in subjects whose IL-6 levels were in the fourth quartile of increasing levels (versus the first quartile) was 2.74 (95% confidence interval 1.94-3.87).",
            "output": [
                "Is interleukin-6 a significant predictor of radiographic knee osteoarthritis : The Chingford Study?"
            ]
        },
        {
            "id": "task847-91bcba156f3c4a5b89656e9a96a5ba1a",
            "input": "Our objective was to study the effect of the genetic background on the wound healing process after myocardial infarction (MI) in mice.', 'MI was induced in five different mouse strains (BalbC, C57Bl6, FVB, 129S6, and Swiss). At 3, 14, and 28 days after MI, cardiac dimensions were monitored by echocardiography and histology, whereas cardiac function was determined by direct intraventricular pressure measurements (dP/dt). Furthermore, matrix metalloproteinases were measured by zymography, and mRNA expression by quantitative PCR. Infarct rupture, which typically occurred at 3-6 days post-MI, was most frequent in 129S6 mice (62%), followed by C57Bl6 (36%), FVB (29%), Swiss (23%), and BalbC (5%). The high incidence of infarct rupture in 129S6 mice was associated with high systolic blood pressure and increased influx of inflammatory cells. Cardiac dilatation was most marked in Swiss mice and least prominent in 129S6 mice. The degree of dilatation was associated with a reduced ejection fraction and decreased dP/dt values at 14 and 28 days post-MI. At day 14 and 28 post-MI, secondary thinning of the infarct area was marked in BalbC, FVB, and Swiss, but absent in C57Bl6 and 129S6 mice. In the latter two groups, this was paralleled by the highest number of myofibroblasts at day 14 post-MI.",
            "output": [
                "Does mouse strain determine the outcome of wound healing after myocardial infarction?"
            ]
        },
        {
            "id": "task847-786b442f5d944745a2e05ff6430b4e09",
            "input": "The tumor necrosis factor (TNF) gene is located within the highly polymorphic major histocompatibility complex region, exhibiting the -308 GA promoter region polymorphism and six microsatellites (TNFa-f) spanning the region nearby the TNF locus.', 'In the present study, we evaluated the frequency of -308 GA and TNFa-e polymorphisms and respective haplotypes (in chromosomal sequence: TNFd-TNFe-308GA-TNFc-TNFa-TNFb), in 222 patients with AIDS, 52 of whom exhibited cytomegalovirus retinitis, and in 202 healthy HIV-negative individuals.', 'TNF microsatellite and single nucleotide polymorphism typings were performed by PCR followed by polyacrylamide gel electrophoresis.', 'The TNF-308A allele and the 4-3-G-2-7-1 haplotype were associated with susceptibility to AIDS, whereas the TNFb4 allele and the 3-3-G-1-11-4 haplotype were associated with protection against AIDS development. The TNFc2 allele and the 4-1-G-2-2-1 haplotype, which contains the TNFc2 allele, were associated with cytomegalovirus retinitis.",
            "output": [
                "Are tumor necrosis factor region polymorphisms associated with AIDS and with cytomegalovirus retinitis?"
            ]
        },
        {
            "id": "task847-ab49d971e4a54025a5c9ca9a3bbd5cb3",
            "input": "Walking is usually undertaken at a speed that coincides with the lowest metabolic cost. Aging however, alters the speed-cost relationship, as preferred walking speeds decrease and energy costs increase. It is unclear to what extent this relationship is affected when older women undertake walking as an exercise modality. The aim of this study was to compare the energetic cost of walking at a self-selected exercise pace for a 30 minute period in older and younger women.', \"The energetic cost of walking was assessed using the energy equivalent of oxygen consumption measured in 18 young (age 25 to 49 years) and 20 older (age 50 to 79 years) women who were asked to walk at their 'normal' exercise pace on a motorized treadmill for 30 minutes duration.\", 'The mass-specific net cost of walking (Cw) was 15% higher and self-selected walking speed was 23% lower in the older women than in the younger group. When speed was held constant, the Cw was 0.30 (J.kg-1.m-1) higher in the older women.",
            "output": [
                "Is walking speed at self-selected exercise pace lower but energy cost higher in older versus younger women?"
            ]
        },
        {
            "id": "task847-b73bfacdcbbd49a19dd1a1bb841cea81",
            "input": "Lysophosphatidylcholine (LPC), an atherogenic component of oxidized low-density lipoprotein, has been shown to induce the attenuation of endothelium-dependent vascular relaxation. Although benidipine, a dihydropyridine-calcium channel blocker, is known to have endothelial protective effects, the effects of benidipine on LPC-induced endothelial dysfunction remain unknown. We examined the effects of benidipine on the impairment of endothelium-dependent relaxation induced by LPC.', 'Benidipine was administered orally to rats and aortas were then isolated. Aortic rings were treated with LPC and endothelial functions were then evaluated. Additionally, the effects of benidipine on intracellular calcium concentration ([Ca2+]i) and membrane fluidity altered by LPC in primary cultured rat aortic endothelial cells were examined. [Ca2+]i was measured using the fluorescent calcium indicator fura-2. Membrane fluidity was monitored by measuring fluorescence recovery after photobleaching.', 'Treatment with LPC impaired endothelial function. Benidipine prevents the impairment of relaxation induced by LPC. Acetylcholine elicited an increase in [Ca2+]i in fura-2 loaded endothelial cells. The increase in [Ca2+]i was suppressed after exposure to LPC. Plasma membrane fluidity increased following incubation with LPC. Benidipine inhibited the LPC-induced increase in membrane fluidity and impairment of increase in [Ca2+]i.",
            "output": [
                "Does the dihydropyridine calcium channel blocker benidipine prevent lysophosphatidylcholine-induced endothelial dysfunction in rat aorta?"
            ]
        },
        {
            "id": "task847-571febf4bd32488681c3ce087173dcd3",
            "input": "Linoleic 18:2 (n-6) and alpha-linolenic 18:3 (n-3) essential fatty acids and long-chain polyunsaturated fatty acids (LC-PUFA) are essential nutrients for growth and neonatal development. Consumption of preformed n-3 LC-PUFA has been shown to increase gestational duration and to decrease the incidence of premature birth in human studies. This study evaluated the association of essential fatty acids and LC-PUFA in breast milk on the growth of premature children (weight, height and head circumference).', 'Thirty-seven premature infants with a gestational age of 37 weeks or less were followed until 6 months of gestational age, adjusted for prematurity. The milk from mothers, weight, height and head circumference measures of children were collected during the follow up. The breast milk fatty acids were quantified by gas-liquid chromatography.', 'Our results showed that total n-3 PUFA was positively associated with weight gain (p = 0.05), height (p = 0.04) and body mass index (BMI) of children (p = 0.05). Our results also indicate that both linoleic acid and total essential fatty acids were positively associated with BMI and head circumference, whereas oleic acid was positively associated only with head circumference.",
            "output": [
                "Is n-3 polyunsaturated fatty acids in milk associate to weight gain and growth in premature infants?"
            ]
        },
        {
            "id": "task847-315d00c9a0044277be1dd3a739e91798",
            "input": "Pharmacoresistance is a common problem hindering treatment of epilepsy. A possible cause for this resistance is the overexpression of efflux drug transporters, e.g. P-glycoprotein (P-gp), which may decrease extracellular antiepileptic drugs levels in brains of intractable epilepsy patients. Another transmembrane drug transporter is the organic anion transporting polypeptide 2 (Oatp2), which is colocalized with P-gp in many polarized tissues. However, a role for Oatp2 in the development of multidrug resistance has not been established. In the present work, we investigated the expression of drug transporters Oatp2 and P-gp in brain, liver and kidney of rats with chronic epilepsy induced by lithium-pilocarpine.', 'Chronic epilepsy was elicited after status epilepticus (SE) induced by lithium-pilocarpine in adult Wistar rats. Following SE, expression of Oatp2 and P-gp protein was detected by immunohistochemistry and Western blot analysis and messenger RNA (mRNA) using reverse transcription polymerase chain reaction (RT-PCR). Levels of the drug transporters were compared in brain, liver and kidney of chronic epileptic and control rats.', 'Both Oatp2 and P-gp were expressed in the brain, liver and kidney but predominantly in the brain. In the brain, Oatp2 and P-gp immunopositive cells were observed in brain capillary endothelium and choroid plexus epithelium. Compared with control rats, Oatp2 protein expression in brain was significantly decreased, while P-gp was obviously increased in chronic epileptic rats. P-gp mRNA was also significantly higher in brains of chronic epileptic rats, whereas the expression of Oatp2 did not change. Organic anion transporting polypeptide 2 and P-gp did not change at the mRNA or protein level with epilepsy in the liver or kidney.",
            "output": [
                "Are drug transporters altered in brain , liver and kidney of rats with chronic epilepsy induced by lithium-pilocarpine?"
            ]
        },
        {
            "id": "task847-95a12c81d7b447f6ae94077d99830713",
            "input": "Prediction of prognosis after liver transplantation (OLT) remains difficult. The present study determines if standard laboratory parameters measured within the first week after OLT correlate with outcome.', 'Laboratory parameters measured within the first weak after OLT of 328 patients were grouped either graft loss or death within 90 days after (group 1: graft loss; group 2: death; group 3: neither graft loss nor death within 90 days).', 'Peak AST and ALT were significantly lower in group 3 (1867 and 1252 U/L) than in group 1 (4474 and 2077 U/L) or 2 (3121 and 1865 U/L). Bilirubin was significantly lower and gamma-GT significantly higher in group 3 compared to groups 1 and 2. In multivariate analysis, high AST peaks were independently associated with death or graft loss within 90 days. An increase in gamma-GT and low bilirubin early after transplantation were found to be independently associated with superior outcome.",
            "output": [
                "Are an early increase in gamma glutamyltranspeptidase and low aspartate aminotransferase peak values associated with superior outcomes after orthotopic liver transplantation?"
            ]
        },
        {
            "id": "task847-21957b4474a2431aa66a46685e3a527d",
            "input": "In diabetics with end-stage renal disease (ESRD), risk of death has been reported to be non-constant after the first dialysis, and different outcomes have been observed between genders. We assessed the impact of type 2 diabetes (T2DM) on mortality in dialysis regarding its differential effect by gender using time-dependent analyses.', 'All T2DM and non-diabetic (no-DM) patients who started dialysis in two renal units in Lyon, France, between January 1, 1995, and December 31, 2007, were included. In multivariate analyses, the Cox model and Shoenfeld residual approach were used to assess the effect of T2DM on dialysis mortality by gender.', 'We included 235 T2DM (males: 57.9%) and 480 no-DM (males: 65.6%) patients. In males, the adjusted hazard ratio (aHR) for death in T2DM versus no-DM was 0.83 (p = 0.20) and was constant over time after the first renal replacement therapy (RRT) (p = 0.88). In females, aHR for death in T2DM versus no-DM patients was not constant over time (p = 0.002). It was 0.64 (p = 0.13) within the first year after the first RRT and 2.10 (p = 0.002) after the first year. Evolutions with time of these aHR by gender were significantly different (p = 0.009).",
            "output": [
                "Does the Impact of type 2 diabetes on mortality in end-stage renal disease patients differ between genders?"
            ]
        },
        {
            "id": "task847-fd51b6be11ec4d8eb4e4471f994f8a54",
            "input": "The Cochrane Central Register of Controlled Trials, PubMed Medline and Latin American and Caribbean Health Science literature databases were searched, and searches made by hand of identified papers, to source relevant data. (BIOSIS Previews) were searched. There were no language restrictions.', 'Studies were evaluated by two reviewers independently. Only clinical trials were included that were published in the English, Spanish and Portuguese languages and were performed on humans. Articles were excluded when the examiners were not calibrated; when they did not compare manual and electronic probing techniques; when they did not measure the clinical attachment level (CAL); and when the subjects did not present destructive periodontal disease or had already received periodontal treatment.', 'The quality of the identified studies was assessed and standardised data extracted. Only two studies met all the selection criteria so no meta-analysis was performed.', 'Only two of the 37 identified articles were included in the review. The results of these two studies showed that the mean variance and the absolute mean difference between CAL measurements for the two types of probes were not statistically different.",
            "output": [
                "Do manual and electronic probes have similar reliability in the measurement of untreated periodontitis?"
            ]
        },
        {
            "id": "task847-54388adb1c8d49989f5c6cc773e04b40",
            "input": "To investigate if placental Doppler velocimetry can predict the recurrence of a small-for-gestational age (SGA) fetus in subsequent pregnancies.', 'Retrospective study.', 'City cohort over 15 years attending a university hospital.', 'A total of 196 pregnancies suspected of a SGA fetus (<3rd percentile) evaluated by uterine and umbilical artery Doppler velocimetry. Blood velocity waveform was analyzed for pulsatility index (PI) as well as the uterine artery waveform for notching in early diastole.', 'The occurrence of a SGA newborn during the succeeding pregnancy by Doppler results from the previous pregnancy.', 'In the group of 196 pregnancies suspected for SGA, 27 (13.8%) delivered a SGA newborn in the following pregnancy. Thirty-seven (18.9%) of the 196 had an abnormally high PI in the uterine arteries in their first pregnancy, 12 (32.4%) of these delivered a SGA child in the next pregnancy (relative risk 3.44, p<0.001). The corresponding figure for those with normal uterine artery PI was 15 (9.4%). Abnormal umbilical artery Doppler was a worse predictor of recurrence of SGA (p=0.051). Uterine artery notching was not related to a SGA newborn during next pregnancy.",
            "output": [
                "Is abnormal uterine artery Doppler in pregnancies suspected of a SGA fetus related to increased risk of recurrence during next pregnancy?"
            ]
        },
        {
            "id": "task847-8bd79b2c525144519b933e01d582fbea",
            "input": "Our aim was to analyze the effects of 3-month antihypertensive therapy by nebivolol, a beta-blocking agent with nitric oxide-mediated vasodilatory properties, on coronary flow reserve (CFR) and left ventricular filling pressure (LVFP) in uncomplicated arterial hypertension.', 'Twenty newly diagnosed, never treated, uncomplicated hypertensive patients (14 male and six female patients, mean age = 49 years), I-II WHO grade, underwent single-blind nebivolol treatment. At baseline and at 3-month follow-up, patients underwent Doppler echocardiography including pulsed Tissue Doppler of septal mitral annulus: the ratio between transmitral E velocity and myocardial early diastolic velocity (E/Em ratio) was calculated as an index of LVFP degree. Transthoracic Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was also determined.', 'After 3-month nebivolol therapy, rate-pressure product decreased (P < 0.0001). No significant change of left ventricular mass index, relative wall thickness and midwall shortening was detected. Left ventricular end-diastolic diameter and stroke volume were both marginally increased. Nebivolol increased Em (P < 0.0001), reduced E/Em ratio (from 9.0 +/- 1.6 to 8.2 +/- 1.1, P < 0.0001) and enhanced CFR (from 2.07 +/- 0.2 to 2.20 +/- 0.2, P = 0.003), because of increased hyperemic coronary flow velocity (P < 0.001). CFR increase remained significant (P < 0.001) after normalizing resting and dipyridamole coronary velocities for the respective rate-pressure product. The increase of normalized CFR induced by nebivolol was related with E/Em ratio decrease (r = -0.65, P < 0.002).",
            "output": [
                "Does nebivolol induce parallel improvement of left ventricular filling pressure and coronary flow reserve in uncomplicated arterial hypertension?"
            ]
        },
        {
            "id": "task847-3c6e8cbcda2b4e35a16ac39b7bd14887",
            "input": "The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D). We used a prospective population-based cohort study to estimate the prevalence of elevated iron indices and hemochromatosis-related morbidity for compound heterozygotes. In all, 31,192 subjects of northern European descent were genotyped for HFE C282Y and H63D. An HFE-genotype stratified random sample of 1,438 subjects, followed for an average of 12 years to a mean age of 65 years, completed questionnaires and gave blood. Clinical examinations were blinded to HFE genotype. A total of 180 (84 males) clinically examined C282Y/H63D participants were compared with 330 (149 males) controls with neither HFE mutation; 132 (65 males) and 270 (122 males), respectively, had serum iron measures at both timepoints. Mean serum ferritin (SF) and transferrin saturation (TS) were significantly greater for male and female compound heterozygotes than for wild-types at baseline and follow-up (all P < 0.02) except for females who were premenopausal at baseline, where SF was similar in both genotype groups. For subjects with serum measures from both baseline and follow-up, mean SF and TS levels did not change significantly for men or for postmenopausal women, but for premenopausal women SF levels increased from 43 to 109 microg/L for compound heterozygotes and from 35 to 64 microg/L for wild-types (both P < 0.001). Male and female compound heterozygotes had a similar prevalence of hemochromatosis-related morbidity to wild-types. One of 82 males and zero of 95 females had documented iron overload-related disease.",
            "output": [
                "Are hFE C282Y/H63D compound heterozygotes at low risk of hemochromatosis-related morbidity?"
            ]
        },
        {
            "id": "task847-ef704f24fd6b42e1ac19872fb1555705",
            "input": "Monocytes are cellular components of wound repair, arteriogenesis, and atherogenesis. Vascular endothelial growth factor (VEGF)-A and placental growth factor recruit monocytes to sites of arteriogenesis via stimulation of VEGF receptor-1 (VEGFR-1). The chemotactic response of monocytes to VEGF-A is attenuated in individuals with diabetes mellitus (DM). This VEGF resistance correlates with impaired collateral growth. The aim of this study is to elucidate the molecular basis of VEGF resistance and impaired monocyte response in DM.', 'Phosphorylation of Akt, p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) could be stimulated with either placental growth factor-1 or VEGF-A in monocytes from non-DM but not DM individuals. In contrast, formyl-methionyl-leucyl-phenylalanine caused a comparable activation of these molecules in both DM and non-DM monocytes. Baseline phosphorylation of Akt, p38, and ERK1/2 was significantly elevated in monocytes from DM compared with non-DM subjects. Of note, H(2)O(2) activated Akt, p38, and ERK1/2 in non-DM monocytes ex vivo. Protein tyrosine phosphatases had stronger oxidative modifications in monocytes from DM than from non-DM individuals, which reflects functional protein tyrosine phosphatase inhibition, similar to that seen after H(2)O(2) challenge. Overall, protein tyrosine phosphatase and protein tyrosine phosphatase-1B activity were reduced in DM monocytes. DM monocytes revealed higher expression of the receptor for advanced glycation end products. Stimulation with advanced glycation end products ligands resulted in activation of non-DM monocytes and inhibition of VEGFR-1-mediated chemotaxis. The elevated baseline phosphorylation/activation of Akt, p38, and ERK1/2 in DM monocytes likely causes the resistance to further stimulation with specific stimuli such as VEGF-A, revealing a molecular explanation of the DM-related signal transduction defect.",
            "output": [
                "Does diabetes mellitus activate signal transduction pathways resulting in vascular endothelial growth factor resistance of human monocytes?"
            ]
        },
        {
            "id": "task847-e1b300f3bd224e5b92c5263d8391a154",
            "input": "Depression predicts prognosis in many cardiac conditions, including congestive heart failure (CHF). Despite heightened cardiac risk in patients with comorbid atrial fibrillation (AF) and CHF, depression has not been studied in this group. This substudy, from the AF-CHF Trial of rate- versus rhythm-control strategies, investigated whether depression predicts long-term cardiovascular mortality in patients with left ventricular ejection fraction <or=35%, CHF symptoms, and AF history who receive optimal medical care.', 'Depression symptoms (Beck Depression Inventory-II) were assessed in 974 participants (833 men), with 32.0% showing elevated scores (Beck Depression Inventory-II >or=14). Over a mean follow-up of 39 months, there were 246 cardiovascular deaths (111 presumed arrhythmic; 302 all-cause deaths). Cox proportional hazards models adjusted for other prognostic factors (including age, marital status, cause of CHF, creatinine level, left ventricular ejection fraction, paroxysmal AF, previous AF hospitalization, previous electrical conversion, and baseline medications) showed that elevated depression scores significantly predicted cardiovascular mortality (primary outcome), arrhythmic death, and all-cause mortality. The adjusted hazard ratios were 1.57 (95% confidence interval 1.20 to 2.07, P<0.001), 1.69 (95% confidence interval 1.13 to 2.53, P=0.01), and 1.38 (95% confidence interval 1.07 to 1.77, P=0.01), respectively. The risks associated with depression and marital status were additive, with the highest risk in depressed patients who were unmarried.",
            "output": [
                "Do elevated depression symptoms predict long-term cardiovascular mortality in patients with atrial fibrillation and heart failure?"
            ]
        },
        {
            "id": "task847-c1b90b8037314745a7d54678005281c3",
            "input": "Significant improvement in myocardial recovery has been shown previously with interventions to decrease reactive oxygen species after ischemia/hypoxia. We investigated whether co-administration of N-acetylcysteine (NAC, a scavenger for reactive oxygen species) and N (G)-monomethyl-L: -arginine (L-NMMA, a non-selective nitric oxide synthase inhibitor) results in better hemodynamic recovery.', 'Controlled, block-randomized study.', 'University research laboratory.', 'Mixed breed piglets (1-4d, 1.6-2.4 kg).', 'Acutely instrumented piglets received normocapnic alveolar hypoxia (10-15% oxygen) for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). After reoxygenation, hypoxic-reoxygenated piglets were given either saline (controls), NAC [30 mg/kg bolus + 20 mg/(kg h) infusion], NMMA [0.1 mg/kg bolus + 0.1 mg/(kg h) infusion] or NAC + L-NMMA via intravenous infusion in a blinded, randomized fashion (n = 8/group). Sham-operated piglets had no hypoxia-reoxygenation (n = 5).', 'Both cardiac index and stroke volume of hypoxia-reoxygenation controls remained depressed during reoxygenation (vs. normoxic baseline, p < 0.05). Post-resuscitation treatment with L-NMMA alone did not improve systemic hemodynamic recovery, but caused pulmonary hypertension (vs. controls). In contrast, treating the piglets with either NAC or NAC + L-NMMA improved cardiac index and stroke volume, with no effect on heart rate and blood pressure (vs. controls). These treatments also decreased various oxidative stress markers in myocardial tissues (vs. controls). However, there was no significant difference between NAC- and NAC + L-NMMA groups in all examined parameters.",
            "output": [
                "Does post-resuscitation NOS inhibition improve hemodynamic recovery of hypoxic newborn pigs?"
            ]
        },
        {
            "id": "task847-ba9e2cbb5baa48da92711a11fc572ad6",
            "input": "The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase (AMPK). Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels. We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes.', 'In an observational cohort study using record-linkage databases and based in Tayside, Scotland, U.K., we identified people with type 2 diabetes who were new users of metformin in 1994-2003. We also identified a set of diabetic comparators, individually matched to the metformin users by year of diabetes diagnosis, who had never used metformin. In a survival analysis we calculated hazard ratios for diagnosis of cancer, adjusted for baseline characteristics of the two groups using Cox regression.', 'Cancer was diagnosed among 7.3% of 4,085 metformin users compared with 11.6% of 4,085 comparators, with median times to cancer of 3.5 and 2.6 years, respectively (P < 0.001). The unadjusted hazard ratio (95% CI) for cancer was 0.46 (0.40-0.53). After adjusting for sex, age, BMI, A1C, deprivation, smoking, and other drug use, there was still a significantly reduced risk of cancer associated with metformin: 0.63 (0.53-0.75).",
            "output": [
                "Are new users of metformin at low risk of incident cancer : a cohort study among people with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-64ecb272fcb3456ebe5d51bcdb558b61",
            "input": "Microalbuminuria is associated with cardiovascular mortality, particularly among individuals with type 2 diabetes, but the mechanisms underlying this association are not completely understood. Microalbuminuria is known to be associated with cardiovascular autonomic dysfunction (C-AD), and C-AD in turn is associated with cardiovascular mortality. The purpose of this study, therefore, was to investigate whether C-AD can explain the relationship between microalbuminuria and cardiovascular mortality.', 'We studied 490 individuals from a population-based cohort of individuals aged 50-75 years who were followed for a median period of 13.6 years. Microalbuminuria was defined as an albumin-to-creatinine ratio > or =2.0 mg/mmol in an early-morning spot-urine sample. Ten parameters reflecting different aspects of cardiovascular autonomic function were measured and compiled into a total score of C-AD (mean of separate z scores). The association between C-AD and microalbuminuria was estimated by multiple linear regression, and relative risks (RRs) for cardiovascular mortality were estimated by Cox proportional hazards analyses.', 'After adjustments for age, sex, glucose tolerance status, and other risk factors, C-AD was associated with microalbuminuria (beta = 0.16 [95% CI 0.01-0.33]), and both microalbuminuria (RR 2.09 [1.07-4.08]) and C-AD (1.74 [1.04-2.89]) were associated with cardiovascular mortality. These associations did not change after further mutual adjustment for C-AD (2.13 [1.09-4.17]) or microalbuminuria (1.76 [1.05-2.94]), respectively.",
            "output": [
                "Are microalbuminuria and cardiovascular autonomic dysfunction independently associated with cardiovascular mortality : evidence for distinct pathways : the Hoorn Study?"
            ]
        },
        {
            "id": "task847-b8ff431cbfd949f79171a6843d47d532",
            "input": "To determine whether fertilization rate serves as a biological assay, reflects oocyte quality, and may be used to help predict patient implantation rate.', 'Retrospective cohort study.', 'Academic center.', 'Couples undergoing 3603 in vitro fertilization (IVF) cycles from 2001 to 2007.', 'None.', 'We compared the implantation rate among cycles with high versus low fertilization rate. Univariate analyses were performed to determine the association of implantation rate with potential confounding variables: age, day-3 follicle-stimulating hormone level, day-3 estradiol level, antral follicle count, oocyte number, cycle attempts, embryo grading, and number of embryos transferred. Multivariate analysis was then performed to determine whether the fertilization rate remained an independent predictor.', 'Cutoffs for fertilization rate were 50% for intracytoplasmic sperm injection (ICSI) and 75% for conventional insemination. Higher ICSI fertilization was statistically significantly associated with the implantation rate (25.2% vs. 17.8 %). After adjusting for variables associated with implantation rate, fertilization rate for ICSI remained a strong independent predictor of implantation. Higher conventional insemination fertilization was statistically significantly associated with implantation (32.1% vs. 25.7%) and remained a statistically significant predictor after adjustment.",
            "output": [
                "Is fertilization rate an independent predictor of implantation rate?"
            ]
        },
        {
            "id": "task847-f86c7aa6c47f451fa10ad8f619f734c5",
            "input": "There are several studies on myocardial tissue Doppler velocities during dobutamine stress, but few studies on the same parameters during bicycle exercise. We wanted to examine how sample sites affected velocities, beat-to-beat variability and segments eligible for analysis.', 'Twenty patients with normal coronary arteries were included in the study. Echocardiograms were obtained at rest and at peak exercise on the exercise bike and were analyzed off line by two independent raters.",
            "output": [
                "Do feasibility of using tissue Doppler velocities in stress echo during upright bicycle exercise?"
            ]
        },
        {
            "id": "task847-96e907c84fba485a9ddcae125c7227f4",
            "input": "NOTES has changed the working environment of endoscopy, leading to new difficulties. The limitations of conventional endoscopes call for the development of new platforms. Robotics may be the answer.', 'The authors compared human to robotized manipulation of a flexible endoscope into the abdominal cavity, in an animal model. Thirty-two participants were enrolled. Results were analyzed according to the clinical background of the participants: experienced endoscopists, experienced laparoscopists, and medical students. Two single-channel gastroscopes were used. Whereas one was not modified, the other had the handling wheels replaced by motors controlled through a computer and a joystick. A NOTES transgastric approach was used to access the peritoneal cavity. The time to touch previously positioned intra-abdominal numbered plastic targets was recorded 3 times with each endoscope.', 'Mean time to complete the tasks was significantly shorter using the conventional endoscope (2.71 vs 6.96 minutes, P < .001). When the robotized endoscope was used, the mean times of endoscopists (7.42 minutes), laparoscopists (6.84 minutes), and students (6.77 minutes) were statistically identical. No differences were found between laparoscopists and students in both techniques.",
            "output": [
                "Are joystick interfaces suitable for robotized endoscope applied to NOTES?"
            ]
        },
        {
            "id": "task847-dafc32e9630148efab8d1b06cf006166",
            "input": "Metastatic prostate cancer is a major cause of death of men in the United States. Expression of met, a receptor tyrosine kinase, has been associated with progression of prostate cancer.', 'To investigate met as a biomarker of disease progression, urinary met was evaluated via ELISA in men with localized (n = 75) and metastatic (n = 81) prostate cancer. Boxplot analysis was used to compare the distribution of met values between each group. We estimated a receiver operating characteristic curve and the associated area under the curve to summarize the diagnostic accuracy of met for distinguishing between localized and metastatic disease. Protein-protein interaction networking via yeast two-hybrid technology supplemented by Ingenuity Pathway Analysis and Human Interactome was used to elucidate proteins and pathways related to met that may contribute to progression of disease.', 'Met distribution was significantly different between the metastatic group and the group with localized prostate cancer and people with no evidence of cancer (P < 0.0001). The area under the curve for localized and metastatic disease was 0.90, with a 95% confidence interval of 0.84 to 0.95. Yeast two-hybrid technology, Ingenuity Pathway Analysis, and Human Interactome identified 89 proteins that interact with met, of which 40 have previously been associated with metastatic prostate cancer.",
            "output": [
                "Do urine analysis and protein networking identify met as a marker of metastatic prostate cancer?"
            ]
        },
        {
            "id": "task847-c63051917ad64d4c9760d8b198e34e9b",
            "input": "Excessive infant crying, or infantile colic, is a common and often stress-inducing problem for parents that can ultimately result in child abuse. From previous research it is known that maternal depression is related to excessive crying, but so far little is known about the influence of paternal depression.', \"In a prospective, population-based study, we obtained information on both maternal and paternal depressive symptoms at 20 weeks of pregnancy by using the Brief Symptom Inventory. Parental depressive symptoms were related to excessive crying in 4426 two-month-old infants. The definition of excessive crying was based on the widely used Wessel's criteria (ie, crying >3 hours for >3 days in the past week).\", 'After adjustment for depressive symptoms of the mother and relevant confounders, we found a 1.29 (95% confidence interval: 1.09-1.52) higher risk of excessive infant crying per SD of paternal depressive symptoms.",
            "output": [
                "Are paternal depressive symptoms during pregnancy related to excessive infant crying?"
            ]
        },
        {
            "id": "task847-5267f484aa114cbba1dc7f772f2f1e41",
            "input": "Spinal anesthesia can be challenging in patients undergoing total joint arthroplasty because of poorly palpable surface landmarks and age-related changes in the lumbar spine. We hypothesized that pre-procedural ultrasound imaging would be effective in identifying the lumbar intervertebral spaces and would provide an accurate measure of the depth to the intrathecal space.', \"Fifty patients undergoing elective total joint arthroplasty were recruited in this prospective descriptive study. Using a curved-array 2-5 MHz transducer, the lumbar spine was imaged in two views, i.e., longitudinal parasagittal (LP) and transverse midline (TM). The intervertebral levels were identified by counting upwards from the sacrum. The locations of the interlaminar spaces were identified by visualizing the ligamentum flavum-dura mater complex and the posterior aspect of the vertebral body. The needle insertion point for a midline approach was determined from the ultrasound examination and was marked on the skin of the patient's back.\", 'The mean patient age was 67 +/- 10 yr, and 46% of the patients had a body mass index >30 kg . m(-2). Surface landmarks were difficult or impossible to palpate in 38% of the patients. The scan quality on the LP and TM views was adequate or better in 100 and 98% of the patients, respectively. Dural puncture was achieved with one needle insertion attempt and within two needle insertion attempts in 84% and 98% of the patients, respectively. The ultrasound-measured depth to the intrathecal space correlated well with the actual needle insertion depth (concordance correlation coefficient = 0.82, accuracy 0.95, precision 0.86), with a tendency to overestimate the depth by just 2.1 +/- 5.4 mm.",
            "output": [
                "Does an ultrasound-assisted approach facilitate spinal anesthesia for total joint arthroplasty?"
            ]
        },
        {
            "id": "task847-99cea636b7984114a73bf031cdaf8dff",
            "input": "High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects.', 'In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3+/-8.9 kg/m(2)) and 20 healthy lean subjects (BMI 22.1+/-1.8 kg/m(2)), UFF and UFE, tetrahydrocortisol (THF), 5alpha-tetrahydrocortisol (5alpha-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5alpha-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight.', 'In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11beta-HSD2 activity after adjustment for gender and BMI (r=0.47, p=0.0002 and r=0.31, p=0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 (p=0.4 and p=0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF (r=0.58, p=0.01 and r=0.55, p=0.02, respectively), whereas urine volume was not associated with 11beta-HSD2 activity after appropriate adjustment (p=0.3).",
            "output": [
                "Is urinary free cortisone , but not cortisol , associated with urine volume in severe obesity?"
            ]
        },
        {
            "id": "task847-ad11dbad448e4d24a79e3c651addba7a",
            "input": "Clinical data have shown that an increased level of serum soluble CD40 ligand (sCD40L) is associated with atherosclerogenesis. We hypothesize that sCD40L induces proliferation and migration of vascular smooth muscle cells (VSMCs) through activation of matrix metalloproteinases (MMPs).', 'Human VSMCs were treated with sCD40L (1 or 5 microg/mL). Cell proliferation and migration were studied using a nonradioactive cell proliferation assay (MTT) and a modified Boyden chamber combined with a scrape-wound assay, respectively. Messenger RNA (mRNA) and protein levels of MMP-2 and MMP-9 were measured with real-time polymerase chain reaction and enzyme-linked immunosorbent assays. Neutralizing antibodies against MMP-2 or MMP-9 were used to evaluate their effects on sCD40L-induced cell proliferation and migration.', 'MTT assay showed a 35% increase in cell proliferation in the high-dose (5 microg/mL) sCD40L-treated group. Cell migration was also increased by 33% (Transwell assay) to 3-fold (scrape-wound assay) after high-dose sCD40L treatment. When cells were treated with 5 microg/mL of sCD40L for 24 hours, significant decreases in MMP-2 and increases in MMP-9 mRNA and protein levels were observed. Neutralizing antibodies against MMP-9 effectively blocked sCD40L-induced cell proliferation and migration.",
            "output": [
                "Does soluble CD40 ligand induce human coronary artery smooth muscle cells proliferation and migration?"
            ]
        },
        {
            "id": "task847-90c9aab0e8bf43b5beb31894a76638b7",
            "input": "Tissue-plasminogen activator (tPA) demonstrated beneficial effects on peritoneal adhesion formation; however, its short half-life limits its continual fibrinolytic effect. Therefore, we delivered adenovirus encoding tPA to prevent adhesions.', 'Rats were subjected to peritoneal injury and assigned to two protocols. In de novo adhesion protocol, adenovirus encoding human tPA gene (Ad-htPA) was instilled after peritoneal injury in group 1 (n = 22), whereas group 2 received phosphate-buffered saline (PBS) (n = 24). In recurrent adhesion protocol, group 1 (n = 15) received the same Ad-htPA dose after adhesiolysis and group 2 (n = 13) received PBS. Adhesion severity was scored 1 week after ad-htPA instillation. Adhesions were analyzed for htPA mRNA by reverse transcription-polymerase chain reaction and levels of htPA, and fibrinolytic inhibitors PAI-1, TIMP-1, and TGF-beta1 were measured using enzyme-linked immunosorbent assay.', 'htPA mRNA and protein were only expressed in adhesions from treated groups. A reduction in adhesion scores (P < .01) and in fibrinolytic inhibitors (P < .001) occurred in the treatment groups. Also, negative correlation was found (r = -.69, P < .01) between adhesion scores and htPA protein, but a positive correlation was found (r = .90, P < .01) between adhesion score and fibrinolytic inhibitors. No bleeding or wound complications were encountered.",
            "output": [
                "Does adenovirus-mediated overexpression of human tissue plasminogen activator prevent peritoneal adhesion formation/reformation in rats?"
            ]
        },
        {
            "id": "task847-959faddaf92a4dd1b3956eb7cbf9c06a",
            "input": "Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia) and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN) are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae.', 'We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ss production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-alpha response.",
            "output": [
                "Does chlamydia pneumoniae hide inside apoptotic neutrophils to silently infect and propagate in macrophages?"
            ]
        },
        {
            "id": "task847-2e57c50de823456f93cdecc14fbdbe1a",
            "input": "Cyclooxygenase-2 inhibitors reduce colon cancer risk by mechanisms that are not fully understood. We performed microarray analysis of adenomas from Apc(Delta14/+) mice to identify genes that respond to these drugs.', 'Apc(Delta14/+) mice were given a single daily injection of parecoxib for up to 9 weeks; intestinal tracts of these and control mice were analyzed by microarray analysis, immunohistochemistry, in situ hybridization, and quantitative real-time polymerase chain reaction. Findings were further assessed using Apc(lox/lox)vil-CreER(T2) mice, the CT26 cancer cell line, and human colon tumor samples.', 'Microarray analysis revealed that osteopontin, a marker of colon cancer progression, was down-regulated in polyps from Apc(Delta14/+) mice given parecoxib compared with controls. Apc(Delta14/+) mice given parecoxib had longer survival times and reduced polyp burdens. Osteopontin was quickly down-regulated by parecoxib in intestinal polyps from Apc(Delta14/+) mice, and 2 components of the osteopontin regulatory network-the orphan nuclear receptor NR4A2 and Wnt/beta-catenin signaling-were sequentially repressed. NR4A2 activated the osteopontin promoter in CT26 cells; this effect was blocked by mutation of the NR4A2 binding response element, cotransfection of a dominant-negative form of NR4A2, and small inhibitory RNA against NR4A2. NR4A2 levels were increased throughout tumor progression in Apc(Delta14/+) mice but, unlike osteopontin, did not correlate with tumor stage. NR4A2 levels were reduced in adenomas from patients treated with rofecoxib.",
            "output": [
                "Do cyclooxygenase-2 inhibitors down-regulate osteopontin and Nr4A2-new therapeutic targets for colorectal cancers?"
            ]
        },
        {
            "id": "task847-ea3a91c52650427fbd6bba0a81b74357",
            "input": "Downstream effects of muscarinic receptor stimulation in intestinal smooth muscle include contraction and intestinal transit. We thought to determine whether classic transient receptor potential (TRPC) channels integrate the intracellular signaling cascades evoked by the stimulated receptors and thereby contribute to the control of the membrane potential, Ca-influx, and cell responses.', 'We created trpc4-, trpc6-, and trpc4/trpc6-gene-deficient mice and analyzed them for intestinal smooth muscle function in vitro and in vivo.', 'In intestinal smooth muscle cells TRPC4 forms a 55 pS cation channel and underlies more than 80% of the muscarinic receptor-induced cation current (mI(CAT)). The residual mI(CAT) depends on the expression of TRPC6, indicating that TRPC6 and TRPC4 determine mI(CAT) channel activity independent of other channel subunits. In TRPC4-deficient ileal myocytes the carbachol-induced membrane depolarizations are diminished greatly and the atropine-sensitive contraction elicited by acetylcholine release from excitatory motor neurons is reduced greatly. Additional deletion of TRPC6 aggravates these effects. Intestinal transit is slowed down in mice lacking TRPC4 and TRPC6.",
            "output": [
                "Does deletion of TRPC4 and TRPC6 in mice impair smooth muscle contraction and intestinal motility in vivo?"
            ]
        },
        {
            "id": "task847-22ede847f0dd4459a7a50d5d65f84c8f",
            "input": "Stem cells within the intestinal epithelium generate daughter cells that undergo lineage commitment and maturation through the combined action of the Wnt and Notch signaling cascades. Both pathways, in turn, regulate transcription factor networks that further define differentiation toward either enterocytes or 1 of 3 secretory cell lineages (Paneth, goblet, or enteroendocrine cells). In this study, we investigated the role of the Wnt-responsive, Ets-domain transcription factor Spdef in the differentiation of goblet and Paneth cells.', 'The in vivo function of Spdef was examined by disrupting the Spdef gene in mice (Spdef(-/-) mice) and analyzing the intestinal phenotype using a range of histologic techniques and DNA microarray profiling.', 'In accordance with expression data, we found that loss of Spdef severely impaired the maturation of goblet and Paneth cells and, conversely, led to an accumulation of immature secretory progenitors. Spdef appears to positively and negatively regulate a specific subset of goblet and Paneth cell genes, including Cryptdins, Mmp7, Ang4, Kallikreins, and Muc2.",
            "output": [
                "Does the ets-domain transcription factor Spdef promote maturation of goblet and paneth cells in the intestinal epithelium?"
            ]
        },
        {
            "id": "task847-74fc6fcdc901450ebb2814e4e8d21602",
            "input": "c-Jun N-terminal kinase (JNK) plays a pivotal role in the development of the metabolic syndrome including nonalcoholic fatty liver disease. However, the mechanism underlying the contribution of JNK to the progression from simple steatosis to steatohepatitis and liver fibrosis is unresolved.', 'Hepatic steatosis, inflammation, and fibrosis were examined in wild-type, jnk1(-/-), or jnk2(-/-) mice fed a choline-deficient L-amino acid-defined (CDAA) diet for 20 weeks. The functional contribution of JNK isoforms in Kupffer cells was assessed in vitro and in vivo using chimeric mice in which the hematopoietic compartment including Kupffer cells was replaced by wild-type, jnk1(-/-), or jnk2(-/-) cells.', 'CDAA diet induced significantly less hepatic inflammation and less liver fibrosis despite a similar level of hepatic steatosis in jnk1(-/-) mice as compared with wild-type or jnk2(-/-) mice. CDAA diet-induced hepatic inflammation was chronic and mediated by Kupffer cells. Pharmacologic inhibition of JNK or gene deletion of jnk1 but not jnk2 repressed the expression of inflammatory and fibrogenic mediators in primary Kupffer cells. In vivo, CDAA diet induced less hepatic inflammation and liver fibrosis despite an equivalent level of hepatic steatosis in chimeric mice with jnk1(-/-) hematopoietic cells as compared with chimeric mice with wild-type or jnk2(-/-) hematopoietic cells.",
            "output": [
                "Does c-Jun N-terminal kinase-1 from hematopoietic cells mediate progression from hepatic steatosis to steatohepatitis and fibrosis in mice?"
            ]
        },
        {
            "id": "task847-b3b3cbdacca546148fefdcd6fa676ac3",
            "input": "Dumping syndrome is a well-described consequence of Roux-en-Y gastric bypass. Although the condition can benefit some patients with morbid obesity, a subset will develop intractable dumping syndrome characterized by symptomatic episodes with most meals. We describe the first series of patients successfully treated endoscopically for intractable dumping syndrome.', 'Endoscopic gastrojejunal anastomotic reduction was performed in patients with intractable dumping syndrome after Roux-en-Y gastric bypass using a combination of argon plasma coagulation, endoscopic suturing, and fibrin glue. The technical feasibility of endoscopic anastomotic reduction and the clinical improvement in dumping symptoms were assessed by clinical follow-up.', 'Endoscopic anastomotic reduction was technically successful in 6 consecutive patients with a dilated gastrojejunal anastomosis and intractable dumping syndrome. One patient reported hematemesis 2 days after the procedure that was treated endoscopically. No other significant complications occurred. Complete and persistent resolution of the dumping symptoms was achieved in all patients, with a median follow-up of 636 days.",
            "output": [
                "Does peroral endoscopic anastomotic reduction improve intractable dumping syndrome in Roux-en-Y gastric bypass patients?"
            ]
        },
        {
            "id": "task847-789bb48c18c742b2a850782e0871c6a8",
            "input": "Up-regulated expression of syndecan-1, a member of the transmembranous proteoglycans that serves as a co-receptor for a wide pool of extracellular ligands, has been ascribed to the promotion of growth of various cancers including breast, ovarian, and endometrial cancers. Here, we have extended these observations to gain insight into correlation between the expression level of syndecan-1 and its tumor-promoting characteristics, particularly, cancer invasion, in endometrial cancer.', 'Human syndecan-1 was stably transfected into three human endometrial cancer cell lines, and its effects were examined with respect to cell survival/proliferation and invasion. In addition, the activation of underlying signaling components, including integrins, focal adhesion kinase (FAK), and nuclear factor kappaB (NF-kappaB) was examined. The activity of NF-kappaB as a transcription factor for matrix metalloproteinase (MMP)-9 was assessed.', 'The innate expression level of syndecan-1 was moderate to high in all endometrial cancer cell lines. Overexpression of syndecan-1 promoted tumor cell proliferation concomitant with the activation of NF-kappaB. Furthermore, overexpression of syndecan-1 markedly enhanced the cancer invasion accompanied by enhanced expression of integrin alphav/beta5 and enhanced phosphorylation of FAK. The transcriptional activation of MMP-9 by NF-kappaB was up-regulated in syndecan-1 overexpression.",
            "output": [
                "Does syndecan-1 enhance the endometrial cancer invasion by modulating matrix metalloproteinase-9 expression through nuclear factor kappaB?"
            ]
        },
        {
            "id": "task847-fbf52fddca374ff4b75c94679135ca4e",
            "input": "Evaluate the influence of composite resin CAD-CAM restoration thickness on the in vitro fatigue resistance and failure mode of overlay-type restoration in endodontically treated premolars.', 'Thirty extracted premolars received root canal treatment followed by a standardized tooth preparation (1.5-, 2.5- or 3.5-mm cusp reduction, proximal gingival margins located 1.5mm below the CEJ, glass-ionomer base and immediately sealed dentin with Optibond FL). Restorations were milled using Cerec3 and FiltekMZ100 composite blocks. The intaglio surfaces of the overlays were sandblasted and silanated. Tooth preparations were sandblasted and etched before insertion of the restoration. All restorations were luted with Optibond FL and preheated FiltekZ100. A closed-loop servohydraulic unit was used for simulating cyclic isometric chewing at 5 Hz, starting with a load of 200 N (5000 cycles), followed by stages of 400, 600, 800, 1000, 1200 and 1400 N at a maximum of 30,000 cycles each. All samples were loaded until fracture or to a maximum of 185,000 cycles. Groups were compared using the Kaplan-Meier survival curves.', 'None of the restored premolars with the 1.5-mm cusp overlap restoration withstood all 185,000 loading cycles. With 2.5- and 3.5-mm cusp overlap, the survival rate was 30% and 40%, respectively. The rate of fracture below the CEJ was 60%, 60% and 30% for 1.5, 2.5 and 3.5 mm of cusp overlap, respectively. Survival of restored premolars with 2.5- and 3.5-mm cusp coverage was not significantly different (p=.23).",
            "output": [
                "Does thickness of CAD-CAM composite resin overlay influences fatigue resistance of endodontically treated premolars?"
            ]
        },
        {
            "id": "task847-b8419adbb3794841ae744f957f2d7f45",
            "input": "Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life.', 'To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined.', 'Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography.', \"Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients' plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies.",
            "output": [
                "Are the metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea influenced by ethanol?"
            ]
        },
        {
            "id": "task847-96b4f3c0fe534a7c98ad8198213492a2",
            "input": "Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro-inflammatory and remodelling-associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus-induced inflammation and remodelling are less known.', 'We investigated whether BUD and FORM synergize in suppressing RV-induced inflammation and remodelling in the airways.', 'In vitro models of RV infection of BEAS-2B and primary normal human bronchial epithelial (NHBE) cells were used. We assessed the effects of individual and combined drugs administered post-infection, at a clinically relevant concentration range (10(-6)-10(-10) m), on the production of CCL5, CXCL10, CXCL8, IL-6 and the remodelling-associated VEGF and bFGF, using ELISA and RT-PCR.', 'BUD effectively suppressed RV-mediated induction of all mediators studied, in a concentration-dependent manner. FORM alone suppressed the production of CXCL8 and bFGF. The combination of BUD and FORM had concentration-dependent, additive or synergistic effects in the suppression of RV-induced CCL5, CXCL8 and CXCL10 in both cell types as well as VEGF in NHBE only. Combination treatment also resulted in an enhanced suppression of RV-induced IL-6, and CCL5 at the mRNA level as compared with BUD or FORM alone.",
            "output": [
                "Do budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus?"
            ]
        },
        {
            "id": "task847-517434861b204582875d358a2b5ae95d",
            "input": "Group 1 allergens from grass pollen (e.g. Phl p 1, the major allergen of timothy grass Phleum pratense) cause IgE reactivity in about 95% of allergic subjects and exist in all grass species. The respiratory epithelium represents a first line of contact of the immune system with airborne allergens, functions as physical barrier and is an important immunological regulation system.', 'The aim of this study was to investigate the interaction of Phl p 1 with human respiratory epithelium to elucidate the contribution of epithelial cells to the development of allergic reactions.', 'Purified Phl p 1 was used to stimulate A549 cells and transient transfected HEK293 cells. mRNA level of different mediators were investigated by real-time PCR, release of the mediators was determined by ELISA. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and an ex vivo model of the murine trachea were used to investigate a potential proteolytic activity of Phl p 1.', 'Phl p 1 activates respiratory epithelial cells as measured by induction of IL-6, IL-8 and TGF-beta mRNA and release. Phl p 1, in contrast to Der p 1 from the house dust mite, does not exert proteolytic activity, as investigated by microscopic observation and MTT test. In an ex vivo model of the murine trachea we were able to show that Der p 1, in contrast to Phl p 1, enhances the transportation velocity of particles by the trachea, presumably by ATP released from the injured epithelium.",
            "output": [
                "Does timothy grass pollen major allergen Phl p 1 activate respiratory epithelial cells by a non-protease mechanism?"
            ]
        },
        {
            "id": "task847-75086d5f224c41959c885be205cb39ba",
            "input": "To assess prospectively the impact of psychiatric disorders on risk for exacerbations. The course of chronic obstructive pulmonary disease (COPD) is punctuated by acute exacerbations. Although anxiety and mood disorders are common in patients with COPD, no studies have assessed prospectively the association between these disorders and exacerbations.', \"Psychiatric disorders were evaluated by a structured psychiatric interview in 110 patients (51% women, age (mean +/- standard deviation) = 66 +/- 8 years) with stable COPD and previous admission for exacerbations recruited from two outpatient clinics. Patients were followed for a mean of 2 years and both inpatient-treated (i.e., treated in the emergency department or hospital) and outpatient-treated (i.e., treated with medication in the patient's own environment) exacerbations were recorded.\", 'Independent of covariates, patients with psychiatric disorders exhibited a significantly higher weighted annual rate of exacerbations treated in an outpatient setting after adjustment for covariates (3 versus 2, p = .003) than patients without psychiatric disorders, but no difference in exacerbations treated in the inpatient setting. They were also at a higher risk for any (relative risk (RR) = 1.56, 95% Confidence Interval (CI) = 1.02-2.37) and outpatient (RR = 1.68, 95% CI = 1.08-2.59) exacerbations, but not inpatient exacerbations (RR = 1.36, 95% CI = 0.82-2.25).",
            "output": [
                "Are chronic obstructive pulmonary disease patients with psychiatric disorders at greater risk of exacerbations?"
            ]
        },
        {
            "id": "task847-53545bfa729747799bbfbe1c64ac06fe",
            "input": "The study was design to explore the health seeking behaviour of Bangladeshi parents for their children during burn injuries.', 'A population-based cross-sectional survey was conducted between January and December 2003 in Bangladesh. Nationally representative data were collected from 171,366 rural and urban households comprising of a total population of 819,429, including 351,651 children of 0-18 years. Mothers or heads of households were interviewed with a structured questionnaire in obtaining the information.', 'About sixty percent parents seek health care from unqualified service providers for their children during a childhood burn injury. Educated and the higher income groups parents choose qualified service provider at significantly higher rate compared to illiterate and poor. Higher proportion of parents of urban residence chooses qualified service provider compared to rural. No significant difference of health seeking behaviour of parent in choosing care provider was found in relation to sex of the children.",
            "output": [
                "Is health seeking behaviour of parents of burned children in Bangladesh related to family socioeconomics?"
            ]
        },
        {
            "id": "task847-c3bad6e4dd8b414ab2d46790e715ab27",
            "input": "To estimate the sensitivity and specificity of emergency department (ED) ultrasound for the detection of solid organ injury following blunt abdominal trauma.', 'A prospective cohort study performed in the ED of an urban Level I trauma center on patients who sustained blunt abdominal trauma. Following initial standard trauma evaluation, patients underwent a secondary ultrasound examination performed specifically to identify injury to the liver or spleen, followed by computed tomography (CT) scan of the abdomen. Ultrasound examinations were performed by emergency medicine residents or attending physicians experienced in the use of ultrasound for detecting hemoperitoneum. Ultrasonographers prospectively determined the presence or absence of liver or spleen injury. CT findings were used as the criterion standard to evaluate the ultrasound results.', 'From July 1998 through June 1999, 152 patients underwent secondary ultrasound examination and CT. Of the 152 patients, nine (6%) had liver injuries and 10 (7%) had spleen injuries. Ultrasound correctly detected only one of the liver injuries for a sensitivity of 11% (95% CI: 0%-48%) and a specificity of 98% (95% CI: 94%-100%). Ultrasound correctly detected eight spleen injuries for a sensitivity of 80% (95% CI: 44%-98%) and a specificity of 99% (95% CI: 95%-100%).",
            "output": [
                "Is emergency Department Ultrasound a Sensitive Detector of Solid Organ Injury?"
            ]
        },
        {
            "id": "task847-e8278c5d05734cf79ef435ea675ef22d",
            "input": "The aim of this study was to examine whether Enterococcus faecalis isolates from endodontic patients (from saliva and from a root canal) are able to prevail against salivary bacteria when grown in coculture in a biofilm reactor.', 'Saliva that was tested to be free of E. faecalis was used as the inoculum. The fate of E. faecalis was examined by using culture techniques and fluorescence in situ hybridization (FISH).', 'The root canal isolate accounted for 37.4% of the biofilm and 31.9% of the planktonic phase when examined by the culture technique, whereas the proportions examined by FISH showed 15.3% in the biofilm and 11.7% in the planktonic phase. The saliva isolate (as examined by the culture technique) accounted for 32.4% in the biofilm and 27.1% in the planktonic phase, respectively, compared with 14.1% in the biofilm and 9.5% in the planktonic phase when examined by FISH analysis.",
            "output": [
                "Do endodontic and salivary isolates of Enterococcus faecalis integrate into biofilm from human salivary bacteria cultivated in vitro?"
            ]
        },
        {
            "id": "task847-76cfe85019e94b58bd3e9e06590f034c",
            "input": "Approximately 12% of bound blood calcium is linked to various anions including phosphate. In patients with end-stage kidney disease (ESKD), serum phosphate is highly variable. We propose that establishing a formula to calculate albumin- and phosphate-corrected total calcium would be more appropriate to estimate free calcium in ESKD patients.', 'In 82 haemodialysis patients, serum ionized calcium (Ca(ion)) and pH were measured by blood gas analyser with ion-selective electrodes at the point-of-care, while bicarbonate, phosphate, albumin, magnesium and total calcium (Ca(tot)) were measured at the central laboratory. Linear regression analysis of measured variables was used to best fit adjusted calcium versus Ca(ion).', 'The most parsimonious multiple linear regression model (r(2) = 0.81) of variables associated with Ca(ion) included Ca(tot) (coeff 0.820, P < 0.0001), albumin (coeff -0.016, P < 0.0001) and phosphate (coeff -0.063, P < 0.002). Modelling of available variables yielded the following equation to adjust calcium for albumin and phosphate: Ca(albPh) = Ca(tot) + (0.015 x (40 - [albumin]) + 0.07 x (1.5 - [phosphate])). At an ambient albumin of 40 g/L, Ca(albPh) would be 0.07 mmol/L lower than Ca(tot) for every mmol/L of phosphate. In vitro data using three different albumin levels and increasing phosphate concentrations demonstrated this relationship, with the slope of the phosphate effect being stronger at lower albumin concentrations.",
            "output": [
                "Is serum phosphate an important determinant of corrected serum calcium in end-stage kidney disease?"
            ]
        },
        {
            "id": "task847-682deec54c89412783f5eca11b646ead",
            "input": "To assess whether nocturnal blood pressure dipping status in type 1 diabetes is correlated with specific sleep characteristics and differences in nocturnal glycemic profiles.', 'Twenty type 1 diabetic adult patients underwent sleep studies with simultaneous 24-h ambulatory blood pressure monitoring and continuous nocturnal glucose monitoring.', 'Altogether, 55% of patients exhibited blunted blood pressure dipping. They did not differ from the dipper group in age, BMI, or systolic (SBP) and diastolic (DBP) blood pressure. Total sleep period (TSP) was higher in the dipper group (497 +/- 30 vs. 407 +/- 44 min for dippers and nondippers, respectively, P < 0.001). TSP was correlated with SBP and DBP day-night differences (r = 0.44 and 0.49, respectively). Periods of nocturnal hypoglycemia (i.e., % of TSP with glycemia <70 mg/dl) were longer in the dipper group (8.1 +/- 10.7 vs. 0.1 +/- 0.4% for dippers and nondippers, respectively, P = 0.02).",
            "output": [
                "Is short sleep duration associated with a blood pressure nondipping pattern in type 1 diabetes : the DIAPASOM study?"
            ]
        },
        {
            "id": "task847-efb3e4251df74fe7a680605498e344da",
            "input": "The objectives of this study were to obtain in-depth qualitative data from patients on the effect of edentulousness and prosthetic rehabilitation upon issues surrounding eating (emotional, social and functional).', '33 patients who had received replacement conventional dentures (CDs) and 33 patients who had received implant-supported mandibular overdentures (ISODs) were interviewed by a researcher outside the clinical team. Interviews focused upon their experience of edentulousness, its management and its impact on their lives. Interviews were transcribed and the qualitative data analysed using NVivo [QSR NVivo v.2.2. Melbourne: QSR International; 2002].', \"Both groups of patients told similar stories about the impact of edentulousness upon eating. A few patients who had received replacement CDs reported significant improvement, but marginal improvements were more common. Most patients who had received ISODs reported a significant positive impact upon eating with very few negative effects reported. The findings suggest that the functional limitations of dentures often impose social restrictions on edentulous patients. Optimising conventional dentures may help, but patients' eating-related quality of life is most likely to be enhanced through the functional improvement and increased social confidence that ISODs bring.",
            "output": [
                "Do a qualitative study on patient perspectives of how conventional and implant-supported dentures affect eating?"
            ]
        },
        {
            "id": "task847-92904a56eb5c4228bdf73b5f675724cc",
            "input": "Calcium ions are highly versatile spacial and temporal intracellular signals of non-excitable cells and have an important impact on nearly every aspect of cellular life controlling cell growth, metabolism, fluid secretion, information processing, transcription, apoptosis, and motility. Neurons and glia respond to stimuli, including neurotransmitters, neuromodulators, and hormones, which increase the intracellular calcium concentration. The function of intracellular calcium in gliomas is unknown. Lots of daily used drugs may act via receptors that can be linked to the intracellular calcium system and therefore could influence glioma biology.', 'Glioma cells were loaded with the calcium ion sensitive dye Fura 2-AM. Subsequently, cells were stimulated with 25 different medical drugs for 30 s. The increase of free intracellular calcium ions was measured and calculated by a microscope-camera-computer-unit.', 'Except for the buffer solution HEPES that served as negative control and for the cortisol derivative dexamethasone, all other 24 tested drugs induced a rise of intracellular calcium ions. The cellular calcium responses were classified into seven functional groups. The tested substances activated several types of calcium channels and receptors.",
            "output": [
                "Do glioblastoma cells express functional cell membrane receptors activated by daily used medical drugs?"
            ]
        },
        {
            "id": "task847-33243701ea5e4beb89465cd1aa556186",
            "input": "Calcium channel blockers (CCBs) inhibit the migration of vascular smooth muscle cells (VSMC) by mechanisms that remain poorly understood. The purpose of the present study was to characterize the signaling mechanisms by which CCBs inhibit VSMC migration.', 'Nifedipine potently inhibited platelet-derived growth factor (PDGF)-induced chemotaxis, collagen I-induced haptotaxis, and wound-induced migration of human aortic VSMC. In addition, nifedipine inhibited PDGF-induced membrane ruffling and lamellipodium formation. PDGF-induced VSMC migration was significantly inhibited by PP2, a selective inhibitor of the Src kinase family, and was also significantly inhibited by the expression of kinase-inactive Src, suggesting that Src is required for VSMC migration. Nifedipine also inhibited PDGF-induced Src activation (by 60+/-4% with 30 microM) and tyrosinephosphorylation of Cas, paxillin, and cortactin, which are actin-associated substrates of Src. RNA interference-induced knockdown of the Ca(2+)-dependent tyrosine kinase, Pyk2, resulted in inhibition of PDGF-induced Src activation and migration. Finally, nifedipine inhibited PDGF-induced Pyk2 activation in a dose-dependent manner.",
            "output": [
                "Does nifedipine interfere with migration of vascular smooth muscle cells via inhibition of Pyk2-Src axis?"
            ]
        },
        {
            "id": "task847-b2bdb95efa6d41489416c08f3944feae",
            "input": "Genistein, a soy component, has been shown to have a biphasic proliferative effect in breast cancer cells, inhibiting in vitro cell proliferation at high concentrations (>10 micromol/l), while stimulating cell proliferation at lower concentrations (<10 micromol/l). However, epidemiological studies have shown an inverse correlation between the intake of genistein and the incidence of breast cancer. One of the possible reasons for this discrepancy could be the differing status of the estrogen receptor (ERalpha and/or ERbeta). Genistein selectively binds to ERbeta with strong affinity and thereby could be a potential chemotherapeutic agent against breast cancer of the ERalpha-negative and ERbeta-positive type. Therefore, the objective of the present study was to determine whether the proliferative effects of genistein were caused by its activity as a selective ERbeta agonist or merely as an antiestrogen.', 'This study was carried out in MDA-MB-231 (ERbeta) and T47D (ERalpha and ERbeta) human breast cancer cells. Cell proliferation was determined by the MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) assay. The cells were grown in estrogen-starved media and exposed to genistein at different concentrations for 72 h, either in the presence or absence of 17beta-estradiol.', 'A significant decrease in cell proliferation was seen in MDA-MB-231 cells at low concentrations of genistein in the presence of 17beta-estradiol, as compared to genistein alone. In T47D cells, which are known to have a predominance of ERalpha over ERbeta, genistein showed a biphasic cell proliferative response both in the presence and absence of 17beta-estradiol.",
            "output": [
                "Does genistein in the presence of 17beta-estradiol inhibit proliferation of ERbeta breast cancer cells?"
            ]
        },
        {
            "id": "task847-da43c66e76e9458ab10a158c236d96f2",
            "input": "To study the antiinflammatory effect of lidocaine in intestinal epithelial cells.', 'HT-29 and T-84 cells were grown in culture with and without TNF-alpha, lidocaine, aconitine and veratridine. The secretion of IL-8 and IP-10 was measured by ELISA. A cDNA microarray was used to assess gene expression. Real-time PCR was used to confirm the results. Western blots and a modified electromobility shift assay (EMSA) were used to assess NFkappaB activation.', 'Lidocaine inhibited spontaneous and TNF-alpha induced secretion of IL-8 and IP-10. The combination of veratridine or aconitine, voltage-gated sodium channels (VGSC) agonists that open VGSCs, with lidocaine did not alter the effect of lidocaine on cytokine secretion. Gene array analysis revealed that IkappaB transcription was induced by TNF-alpha and inhibited by lidocaine. IkappaB real-time PCR confirmed this observation. A Western blot analysis demonstrated that the degradation of IkappaB following TNF-alpha treatment was markedly inhibited by lidocaine. Lidocaine treatment resulted in decreased generation of phosphorylated IkappaB. A modified EMSA was complementary and demonstrated marked inhibition of NFkappaB nuclear binding.",
            "output": [
                "Does lidocaine inhibit epithelial chemokine secretion via inhibition of nuclear factor kappa B activation?"
            ]
        },
        {
            "id": "task847-bec55a17c57b4fd1b3da62c81c451ee2",
            "input": "Tissue factor (TF) contributes to thrombosis following plaque disruption in acute coronary syndromes (ACS). Aim of the study was to investigate the impact of plasma TF activity on prognosis in patients with ACS.', 'One-hundred seventy-four patients with unstable Angina pectoris (uAP) and 112 patients with acute myocardial infarction (AMI) were included with a mean follow up time of 3.26 years. On admission, plasma TF activity was assessed. Patients were categorized into 2 groups: a high-TF activity group with TF >24 pmol/L and low TF activity group with TF \u2264 24 pmol/L. Fifteen cardiovascular deaths occurred in the uAP group and 16 in the AMI group. In AMI TF activity was 24,9 \u00b1 2,78 pmol/l (mean \u00b1 SEM) in survivors and 40,9 \u00b1 7,96 pmol/l in nonsurvivors (P = 0.024). In uAP no differences were observed (25.0 \u00b1 8.04 pmol/L nonsurvivors vs. 25.7 \u00b1 2.14 pmol/L survivors; P = 0.586). Kaplan-Meier estimates of survival at 3.26 years regarding TF activity in AMI were 81.3% and 92.2% with an hazard ratio of 3.02 (95% CI [1.05-8.79], P = 0.03). The Cox proportional hazards model adjusting for correlates of age and risk factors showed that plasma TF activity was an independent correlate of survival (hazard ratio 9.27, 95% CI [1.24-69.12], P = 0.03). In an additional group of patients with uAP and AMI, we identified circulating microparticles as the prevailing reservoir of plasma TF activity in acute coronary syndromes.",
            "output": [
                "Does plasma TF activity predict cardiovascular mortality in patients with acute myocardial infarction?"
            ]
        },
        {
            "id": "task847-a7d5942e3ce14fef959d3ad6a4ff5121",
            "input": "With advances in medicine, the subjective assessment of patients on hemodialysis regarding their quality of life (QOL) is gaining importance. Clinicians cannot rely solely on objective markers, such as the rates of complications and mortality, when evaluating responses to dialysis. In clinical settings, laboratory values are used as measures of patients' health. However, the relationship between clinical laboratory values and QOL has not been elucidated yet. Therefore, the present study aimed to define the relationship of laboratory values and patient attributes to the QOL of outpatients on hemodialysis in order to obtain basic data for reevaluating nursing support for patients on hemodialysis in the future.\", 'The participants were 44 outpatients receiving hemodialysis at Hospital B. The QOL was surveyed using a self-administered questionnaire, the Kidney Disease Quality of Life Short Form. The following patient attributes and laboratory values were taken from the medical records: age; sex; primary disease; number of years on hemodialysis; complications; number of hours of hemodialysis per session; percentage weight gain; cardiothoracic ratio; blood pressure; hematocrit; and the serum levels of albumin, potassium, phosphorus, and calcium.', 'The serum potassium level significantly affected mental health, social functioning, symptoms, and the effect of kidney disease, with the 3.5-5.0 mEq/L target range group scoring higher than the > or =5.1 mEq/L group.",
            "output": [
                "Does the relationship of clinical laboratory parameters and patient attribute to the quality of life of patients on hemodialysis?"
            ]
        },
        {
            "id": "task847-ecf0e59a2a584ba6af862f85838a94cd",
            "input": "The aim of this exploratory study was to identify those factors associated with asthma control assessed according to GINA Guidelines.', '809 (56% female) subjects with asthma were recruited consecutively from both specialist and primary care centres. Asthma control was assessed over a 4-week follow-up period using a composite measure. A multivariate analysis was performed, in which asthma control was included as the dependent variable and several explanatory variables were included as independent variables.', 'Analysis performed on the whole population rendered gender (p=0.003), the type of physician (p<0.001), and age group (p<0.001), as significant factors associated with asthma control. In adults, gender (p=0.001), asthma severity (p<0.001), and type of physician (p<0.001) were significant, and only asthma severity was significant (p=0.043) in children.",
            "output": [
                "Are women , patients with severe asthma , and patients attended by primary care physicians , at higher risk of suffering from poorly controlled asthma?"
            ]
        },
        {
            "id": "task847-51f11cef5af94ffeb35c907c1bb702dd",
            "input": "To investigate whether tafluprost, which is a prostaglandin-related compound and an anti-glaucoma drug, has a direct anti-apoptotic effect in cultured retinal ganglion cells (RGCs) and rat RGCs in retinas with optic nerve crush (ONC).', 'RGC-5 cells were induced to undergo apoptosis by a serum deprivation and by exogenous glutamate. The level of cell death with or without tafluprost was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in intracellular calcium ([Ca(2+)]i) levels were measured with fluo-4 fluorescence. Rat RGCs were degenerated by ONC. After topical instillation of tafluprost for 7 and 14 days, the numbers of retrograde-labeled RGCs were counted. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells.', 'Tafluprost dose-dependently promoted RGC-5 cell viability with an optimum concentration of 3 microM (p = 0.006). Tafluprost significantly reduced caspase-3-positive cells and suppressed [Ca(+2)]i evoked by exogenous glutamate. The cGMP-dependent protein kinase inhibitor and KT-5823 partially blocked the rescue effect of tafluprost (p = 0.002). The survival rate of RGCs significantly increased in eyes treated with tafluprost (p = 0.01), and the prevalence of TUNEL-positive cells was significantly decreased 14 days after ONC (p < 0.001).",
            "output": [
                "Does tafluprost protect rat retinal ganglion cells from apoptosis in vitro and in vivo?"
            ]
        },
        {
            "id": "task847-983dc18dd7b04d8687d7fd3d4021b596",
            "input": "To compare quantitative T2 relaxometry of cerebral white matter (WM) with qualitative assessment of conventional T2-weighted magnetic resonance (MR) images, to assess the relationship between cerebral WM T2 and region-specific apparent diffusion coefficient (ADC), and to examine WM T2 regional variation in preterm infants at term.', 'The local ethical committee granted ethical permission for this study; informed parental consent was obtained for each infant. Sixty-two preterm infants born at less than 32 weeks gestation and nine control infants were examined at 1.5 T; T2-weighted fast spin-echo MR images, T2 relaxometry data, and diffusion-weighted MR images were acquired. Conventional T2-weighted MR images were assessed by a pediatric neuroradiologist for diffuse excessive high signal intensity (DEHSI) in WM. Regions of interest were positioned in frontal WM, central WM, and posterior WM at the level of the centrum semiovale.', 'In preterm infants at term, T2 was longer in all WM regions than in control infants; in infants with DEHSI, T2 was longer than in infants without DEHSI and control infants, with posterior WM T2 being longer than central or frontal WM T2. In control infants, T2 was similar in all WM regions. Frontal and posterior WM ADCs were higher in preterm infants at term than in control infants.",
            "output": [
                "Is t2 at MR imaging an objective quantitative measure of cerebral white matter signal intensity abnormality in preterm infants at term-equivalent age?"
            ]
        },
        {
            "id": "task847-e97056fc533541f8ae152805883e2c47",
            "input": "Isoliquiritigenin is a chalcone derivative with potential in cancer chemoprevention. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent, some cancer cells are resistant to TRAIL treatment. Current studies have tried to overcome TRAIL-resistant cancer cells. Here, we show for the first time that isoliquiritigenin overcomes TRAIL resistance in colon cancer HT29 cells.', 'HT29 cells were treated with isoliquiritigenin and/or TRAIL, and apoptosis induction was detected by flow cytometry and fluorescence microscopy. Protein expression relating to the TRAIL pathway was analyzed by Western blotting.', 'A single treatment with isoliquiritigenin scarcely induced apoptosis in HT29 cells. Combined treatment with suboptimal concentrations of isoliquiritigenin and TRAIL markedly induced apoptosis, however. The effect was blocked by a pan-caspase inhibitor and a caspase-3, 8, 9, or 10 inhibitor, suggesting that the combination facilitates caspase-dependent apoptosis. Furthermore, the apoptosis induced by isoliquiritigenin and TRAIL was blocked by a dominant negative form of the TRAIL receptor. This result indicates that the combined effect is caused by specific interaction between TRAIL and its receptors. Isoliquiritigenin increased the amount of DR5 protein among TRAIL receptors. Isoliquiritigenin did not significantly increase levels of the Bcl-2 family proteins Bcl-2, Bcl-xL, and BAX.",
            "output": [
                "Does combination of isoliquiritigenin and tumor necrosis factor-related apoptosis-inducing ligand induce apoptosis in colon cancer HT29 cells?"
            ]
        },
        {
            "id": "task847-3ffaad5c8a34416fa5a1a6161edcd562",
            "input": "Immediate allergic reactions to beta-lactam antibiotics are mediated by specific IgE antibodies. The Phadia CAP System FEIA is a commercial method for quantification of specific IgE. We wished to determine anti-beta-lactam IgE antibodies in patients without penicillin allergy but with high levels of total IgE.', 'Sera from 41 patients (31 with high total IgE, 10 with low total IgE) were analyzed for IgE antibodies specific to penicilloyl G, penicilloyl V, amoxicilloyl and ampicilloyl using the CAP FEIA((R)) method that was available up to 2006. Seven sera that tested positive were rechecked in a new improved system available after 2006.', 'In patients without a history of penicillin allergy, the specificities of commercial tests for anti-beta-lactam IgE antibodies were 100%, 60%, 27% and 20% at total IgE levels of 8-263 kU/l, 500-664 kU/l, 1000-2000 kU/l and > 2000 kU/l, respectively. In seven retested sera, only 2 (28%) were still positive for penicillin-specific IgE antibody.",
            "output": [
                "Does the specificity of tests for anti-beta-lactam IgE antibodies decline progressively with increase of total serum IgE?"
            ]
        },
        {
            "id": "task847-9ceba7667dc9456da54295fc5de967bb",
            "input": "Genes essential for bacterial growth are of particular scientific interest. Many putative essential genes have been identified or predicted in several species, however, little is known about gene expression requirement stringency, which may be an important aspect of bacterial physiology and likely a determining factor in drug target development.', 'Working from the premise that essential genes differ in absolute requirement for growth, we describe silencing of putative essential genes in E. coli to obtain a titration of declining growth rates and transcript levels by using antisense peptide nucleic acids (PNA) and expressed antisense RNA. The relationship between mRNA decline and growth rate decline reflects the degree of essentiality, or stringency, of an essential gene, which is here defined by the minimum transcript level for a 50% reduction in growth rate (MTL(50)). When applied to four growth essential genes, both RNA silencing methods resulted in MTL(50) values that reveal acpP as the most stringently required of the four genes examined, with ftsZ the next most stringently required. The established antibacterial targets murA and fabI were less stringently required.",
            "output": [
                "Do concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli?"
            ]
        },
        {
            "id": "task847-f21fef09e68d4046a75d8b85776b9661",
            "input": "The use of Salmonella to deliver heterologous antigens from DNA vaccines is a well-accepted extension of the success of oral Salmonella vaccines in animal models. Attenuated S. typhimurium and S. typhi strains are safe and efficacious, and their use to deliver DNA vaccines combines the advantages of both vaccine approaches, while complementing the limitations of each technology. An important aspect of the basic biology of the Salmonella/DNA vaccine platform is the relative contributions of prokaryotic and eukaryotic expression in production of the vaccine antigen. Gene expression in DNA vaccines is commonly under the control of the eukaryotic cytomegalovirus (CMV) promoter. The aim of this study was to identify and disable putative bacterial promoters within the CMV promoter and evaluate the immunogenicity of the resulting DNA vaccine delivered orally by S. typhimurium.', 'The results reported here clearly demonstrate the presence of bacterial promoters within the CMV promoter. These promoters have homology to the bacterial consensus sequence and functional activity. To disable prokaryotic expression from the CMV promoter a series of genetic manipulations were performed to remove the two major bacterial promoters and add a bacteria transcription terminator downstream of the CMV promoter. S. typhimurium was used to immunise BALB/c mice orally with a DNA vaccine encoding the C-fragment of tetanus toxin (TT) under control of the original or the modified CMV promoter. Although both promoters functioned equally well in eukaryotic cells, as indicated by equivalent immune responses following intramuscular delivery, only the original CMV promoter was able to induce an anti-TT specific response following oral delivery by S. typhimurium.",
            "output": [
                "Is bacterial antigen expression an important component in inducing an immune response to orally administered Salmonella-delivered DNA vaccines?"
            ]
        },
        {
            "id": "task847-b9181f644e004fa89593fccc96aef656",
            "input": "The aim of this study was to evaluate the changes in the levels of vasoactive eicosanoid hormone-like substances PGE2, PGI2 and TXA2 in hemodialysis (HD)patients who were following a long-term physical training program during the hemodialysis session.', 'A total of 50 patients with Chronic Kidney Disease (CKD) (stage 5)on hemodialysis and 35 healthy individuals who served as controls (C) were evaluated. The 50 CKD patients were divided into two groups: the HD group consisted of 31 patients who received usual care without any physical activity during the hemodialysis sessions, while group HD/Exer included 19 patients who followed a program of physical exercise for six months. Plasma levels of PGE2, 6-Keto-PGF1alpha (the stable derivative of PGI2) and TXB2 (the stable derivative of TXA2) were measured by reliable enzymo-immunoassay methods (EIA) in HD and HD/Exer patients before and after the hemodialysis sessions as well as in the group of C.', 'The plasma levels of PGE2 and 6-keto-PGF1alpha in group HD Exer/before patients were higher than those in group HDbefore (20.39+/-5.82 and 1449.19+/-553.41 vs 17.68+/-5.36 and 1295.10+/-384.43 pg/ml, p=0.044 and p=0.067, respectively), while the plasma levels of TXB2 were lower in HD Exer/before patients compared to HDbefore(499.76+/-67.51 vs 608.01+/-80.23 pg/ml, p=0.041). The plasma levels of PGE2 and 6-keto-PGF1alpha in group HD Exer/after patients were significantly higher compared to those in HDafter patients (23.01+/-5.70 and 1618.19+/-435.07 vs 16.57+/-4.97 and 1005.44+/-317.16 pg/ml, p<0.001 and p<0.040, respectively). However, significantly lower values in the plasma levels of TXB2 in HD Exer/after compared to HDafter patients (363.10+/-51.91 vs 439.75+/-62.34 pg/ml, p=0.030) were detected. As expected, PGE2 and 6-keto-PGF1alpha values were lower in C than in the groups of patients with CKD.",
            "output": [
                "Does physical training in patients on hemodialysis have a beneficial effect on the levels of eicosanoid hormone-like substances?"
            ]
        },
        {
            "id": "task847-90601cd70df541958f4995a309b9d37d",
            "input": "Evolutionary relationships among the 11 extant orders of insects that undergo complete metamorphosis, called Holometabola, remain either unresolved or contentious, but are extremely important as a context for accurate comparative biology of insect model organisms. The most phylogenetically enigmatic holometabolan insects are Strepsiptera or twisted wing parasites, whose evolutionary relationship to any other insect order is unconfirmed. They have been controversially proposed as the closest relatives of the flies, based on rDNA, and a possible homeotic transformation in the common ancestor of both groups that would make the reduced forewings of Strepsiptera homologous to the reduced hindwings of Diptera. Here we present evidence from nucleotide sequences of six single-copy nuclear protein coding genes used to reconstruct phylogenetic relationships and estimate evolutionary divergence times for all holometabolan orders.', 'Our results strongly support Hymenoptera as the earliest branching holometabolan lineage, the monophyly of the extant orders, including the fleas, and traditionally recognized groupings of Neuropteroidea and Mecopterida. Most significantly, we find strong support for a close relationship between Coleoptera (beetles) and Strepsiptera, a previously proposed, but analytically controversial relationship. Exploratory analyses reveal that this relationship cannot be explained by long-branch attraction or other systematic biases. Bayesian divergence times analysis, with reference to specific fossil constraints, places the origin of Holometabola in the Carboniferous (355 Ma), a date significantly older than previous paleontological and morphological phylogenetic reconstructions. The origin and diversification of most extant insect orders began in the Triassic, but flourished in the Jurassic, with multiple adaptive radiations producing the astounding diversity of insect species for which these groups are so well known.",
            "output": [
                "Do single-copy nuclear genes resolve the phylogeny of the holometabolous insects?"
            ]
        },
        {
            "id": "task847-c0f8364052d240df9ea227c18d46379c",
            "input": "Different classes of small RNAs (sRNAs) refine the expression of numerous genes in higher eukaryotes by directing protein partners to complementary nucleic acids, where they mediate gene silencing. Plants encode a unique class of sRNAs, called trans-acting small interfering RNAs (tasiRNAs), which post-transcriptionally regulate protein-coding transcripts, as do microRNAs (miRNAs), and both sRNA classes control development through their targets. TasiRNA biogenesis requires multiple components of the siRNA pathway and also miRNAs. But while 21mer siRNAs originating from transgenes can mediate silencing across several cell layers, miRNA action seems spatially restricted to the producing or closely surrounding cells.', 'We have previously described the isolation of a genetrap reporter line for TAS3a, the major locus producing AUXIN RESPONS FACTOR (ARF)-regulating tasiRNAs in the Arabidopsis shoot. Its activity is limited to the adaxial (upper) side of leaf primordia, thus spatially isolated from ARF-activities, which are located in the abaxial (lower) side. We show here by in situ hybridization and reporter fusions that the silencing activities of ARF-regulating tasiRNAs are indeed manifested non-cell autonomously to spatially control ARF activities.",
            "output": [
                "Do endogenous TasiRNAs mediate non-cell autonomous effects on gene regulation in Arabidopsis thaliana?"
            ]
        },
        {
            "id": "task847-bd52e2231f834ef389476160bf1d2f06",
            "input": "The epithelial cell-derived protein thymic stromal lymphopoietin stimulates dendritic and mast cells to promote proallergic T(H)2 responses. Studies of transgenic expression of thymic stromal lymphopoietin and its receptor knockout mice have emphasized its critical role in the development of allergic inflammation. Association of genetic variation in thymic stromal lymphopoietin with IgE levels has been reported for human subjects.', 'The aim of this study was to evaluate the relationship between variants of thymic stromal lymphopoietin and asthma and related phenotypes.', 'We selected 6 single nucleotide polymorphisms in thymic stromal lymphopoietin and genotyped 5565 individuals from 4 independent asthma studies and tested for association with asthma, atopy, atopic asthma, and airway hyperresponsiveness by using a general allelic likelihood ratio test. P values were corrected for the effective number of independent single nucleotide polymorphisms and phenotypes.', 'The A allele of rs1837253, which is 5.7 kb upstream of the transcription start site of the gene, was associated with protection from asthma, atopic asthma, and airway hyperresponsiveness, with the odds ratios and corrected P values for each being 0.79 and 0.0058; 0.75 and 0.0074; and 0.76 and 0.0094, respectively. Associations between thymic stromal lymphopoietin and asthma-related phenotypes were the most statistically significant observations in our study, which has to date examined 98 candidate genes. Full results are available online at http://genapha.icapture.ubc.ca/.",
            "output": [
                "Is a thymic stromal lymphopoietin gene variant associated with asthma and airway hyperresponsiveness?"
            ]
        },
        {
            "id": "task847-5a26287018494e8e9b44fe4822286a13",
            "input": "Eosinophils are key players in T(H)2-driven pathologies, such as allergic lung inflammation. After IL-5- and eotaxin-mediated tissue recruitment, they release several cytotoxic and inflammatory mediators. However, their exact contribution to asthma remains controversial. Indeed, in human subjects anti-IL-5 treatment inhibits eosinophilia but not antigen-induced airway hyperresponsiveness (AHR). Likewise, lung fibrosis is abrogated in 2 strains of eosinophil-deficient mice, whereas AHR is inhibited in only one of them. Finally, eosinophils have been shown to attract T(H)2 lymphocytes at the inflammatory site.', 'The ability of eosinophils to promote AHR and lung inflammation independently of lymphocytes was investigated.', 'Adoptive transfers of resting or activated eosinophils from IL-5 transgenic mice were performed into naive BALB/c mice, mice with severe combined immunodeficiency, and IFN-gamma-deficient BALB/c recipients.', 'Adoptively transferred eosinophils induced lung inflammation, fibrosis, collagen deposition, and AHR not only in BALB/c mice but also in recipient mice with severe combined immunodeficiency. Surprisingly, IFN-gamma expression was increased in lungs from eosinophil-transferred animals. Furthermore, IFN-gamma neutralization in recipients partially inhibited eosinophil-induced AHR. Moreover, IFN-gamma-deficient eosinophils or eosinophils treated with a blocking anti-IFN-gamma receptor antibody failed to induce AHR in IFN-gamma-deficient recipients. Finally, in vitro and at low concentrations, IFN-gamma increased eosinophil peroxidase release, potentiated chemotaxis, and prolonged survival, suggesting the existence of an autocrine mechanism.",
            "output": [
                "Does eosinophil-derived IFN-gamma induce airway hyperresponsiveness and lung inflammation in the absence of lymphocytes?"
            ]
        },
        {
            "id": "task847-d8b5bb69dc7a45499b5c7f9d30219cef",
            "input": "To determine whether frontal white matter diffusion abnormalities can help predict acute executive function impairment after mild traumatic brain injury (mTBI).', 'This study had institutional review board approval, included written informed consent, and complied with HIPAA. Diffusion-tensor imaging and standardized neuropsychologic assessments were performed in 20 patients with mTBI within 2 weeks of injury and 20 matched control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) images (imaging parameters: 3.0 T, 25 directions, b = 1000 sec/mm(2)) were compared by using whole-brain voxelwise analysis. Spearman correlation analyses were performed to evaluate associations between diffusion measures and executive function.', 'Multiple clusters of lower frontal white matter FA, including the dorsolateral prefrontal cortex (DLPFC), were present in patients (P < .005), with several clusters also demonstrating higher MD (P < .005). Patients performed worse on tests of executive function. Lower DLPFC FA was significantly correlated with worse executive function performance in patients (P < .05).",
            "output": [
                "Does diffusion-tensor imaging implicate prefrontal axonal injury in executive function impairment following very mild traumatic brain injury?"
            ]
        },
        {
            "id": "task847-8a831e02165b491d8dce12daa254d528",
            "input": "Recently we have shown that the imunoglobulins G from blood serum of some multiple sclerosis patients are capable of cleaving histone H1.', 'To check whether histone H1-hydrolyzing abzymes could be detected not only in blood plasma of autoimmune patients, but also during cancer development, particularly during the onset of multiple myeloma.', \"Immunoglobulines were isolated from blood serum of multiple myeloma patients (n = 11) by precipitation with 50% ammonium sulfate and tested for proteolytic activity toward linker and core calf thymus histones. Antibody preparations able to cleaved histone H1 were subjected to affinity chromatography on histone H1-Sepharose with following analysis of chromatographic fractions' protease activity. To prove that antibody molecules are responsible for hydrolysis of histone H1, gel filtration at acidic pH with subsequent examination of protease activity of chromatographic fractions (pH-shock analysis) was used.\", 'It was found that 3 of 11 antibody preparations are capable of hydrolyzing calf thymus histone H1 but not core histones. It was shown that histone H1-hydrolysing activity of 2 proteolytically active antibody preparations is associated with IgGs that possess affinity towards histone H1. pH-shock analysis proved that protease activity towards histone H1 is intrinsic property of IgG molecules.",
            "output": [
                "Are blood serum immunoglobulins of patients with multiple myeloma capable of hydrolysing histone H1?"
            ]
        },
        {
            "id": "task847-ca392f1714144116a31fc749771a65c0",
            "input": "Severe mitral regurgitation (MR) reduces left atrial thrombus formation in patients with mitral stenosis (MS) and atrial fibrillation (AF). Plasma D-dimer levels represent a biochemical marker for fibrinolytic activity in prothrombotic states. The prothrombotic burden in patients with mitral valve disease and/or AF was assessed using plasma D-dimer levels.', 'The study population included 89 patients with mitral valve disease, 21 with AF but normal valves, and 15 healthy controls. The mitral valve group was subdivided into patients with MS (n = 27), severe MR (n = 26), and MS with concomitant with severe MR (MS/MR; n = 36). These subgroups were further subdivided according to the atrial rhythm (sinus rhythm (SR)+AF).', 'The mean left atrial size was increased in all groups with cardiac disease. D-dimer levels were highest in the MS+AF subgroup (527 +/- 134 microg/l). Patients with MS+AF, MS+SR, and nonvalvular AF had significantly higher D-dimer levels than controls (p < 0.01, by ANOVA). Patients with MR had normal levels of D-dimer. The atrial rhythm did not influence D-dimer levels in the MS/MR subgroup, or in the pure MR subgroup (p = NS).",
            "output": [
                "Does mitral regurgitation reduce systemic coagulation activity in patients with rheumatic heart disease?"
            ]
        },
        {
            "id": "task847-1e2b04913517462dac6b7c7d3852bc83",
            "input": "The effect of alcohol consumption on the liver is controversial. Recent reports have suggested that moderate alcohol consumption decreases the prevalence of elevated alanine aminotransferase levels. The role of alcohol consumption in the development of fatty liver (FL), however, has not been studied definitively. The aim of this study was to examine the association between alcohol consumption and FL in a large Japanese population.', 'A total of 7,431 asymptomatic male subjects who underwent a complete medical survey in our institute between May 2007 and July 2008 were recruited. Cases positive for hepatitis B or C viruses, potential hepatotoxic drug intake, or under treatment for metabolic disorders were excluded. FL was defined by ultrasonography. Visceral and subcutaneous adipose tissues (VAT and SAT) were measured by computed tomography. Independent and significant predictors associated with FL were determined by multiple logistic regression analysis.', 'Of the initial study candidates, 130 (1.7%) were positive for hepatitis B and 66 (0.8%) were positive for hepatitis C. On the basis of the inclusion and exclusion criteria, 5,599 men (50.9+/-8.1 years) were studied cross-sectionally. Light (40-140 g/week) and moderate (140-280 g/week) alcohol consumption significantly and independently reduced the likelihood of FL (odds ratio=0.824 and 0.754, 95% confidence interval=0.683-0.994 and 0.612-0.928, P=0.044 and 0.008, respectively) by multivariate analysis after adjusting for potential confounding variables. VAT, SAT, low-density lipoprotein, triglycerides, and fasting blood glucose were significant predictors of the increased prevalence of FL, whereas age was a predictor of the decreased prevalence of FL.",
            "output": [
                "Does light and moderate alcohol consumption significantly reduce the prevalence of fatty liver in the Japanese male population?"
            ]
        },
        {
            "id": "task847-f53456e108d64dfaaa35acc18fa78ae0",
            "input": "The objective of this study was to investigate the long-term effect of intraoperative application of steroid suspension and coating of the electrode contacts with a thin film of iridium oxide on the intracochlear impedance development after cochlear implantation and on the impedance difference before and after stimulation.', 'Time-dependent development of intracochlear impedances was investigated in 4 different groups of adult patients up to 4 years after implantation. Additionally, during rehabilitation period just after first fitting, impedances before and after stimulation were measured as to investigate the influence of electrical stimulation on the impedances. Results from standard Nucleus 24 Contour (control), standard Nucleus 24 Contour with intraoperative application of steroids, iridium-coated Nucleus 24 Contour, and iridium-coated Nucleus 24 Contour with intraoperative application of steroids were compared.', 'Steroid application reduced impedances significantly throughout the observation period of up to 4 years after implantation. Iridium oxide coating had no effect. Differences between the groups were mainly found on the basal and middle parts of the cochlea, but not close to the tip of the array, also indicating that postoperative fibrous tissue growth is stronger in the basal region of the cochlea. Group mean values of the stimulation effect were not influenced by the different treatments. Nevertheless, only in both steroid-treated groups a correlation between the impedance before stimulation and the stimulation effect was found.",
            "output": [
                "Do the long-term effects of modified electrode surfaces and intracochlear corticosteroids on postoperative impedances in cochlear implant patients?"
            ]
        },
        {
            "id": "task847-1f03e9ca8c1246b1bfe246c88728f644",
            "input": "Infection of human immunodeficiency virus (HIV) has been associated with several chronic diseases, including pulmonary artery hypertension and atherosclerosis. However, the underlying mechanisms of these vascular complications are largely unknown. The objective of this study was to test a novel hypothesis that HIV Nef, an accessory HIV protein, may directly affect endothelial functions and gene expression in pulmonary arteries.', 'Fresh porcine pulmonary artery rings and human pulmonary artery endothelial cells (HPAECs) were treated with HIV Nef for 24 h. With a myograph device, vasomotor function was determined with thromboxane A2 analog, U46619, for contraction, bradykinin, and sodium nitroprusside for relaxation. The expression of endothelial nitric oxide synthase (eNOS) was determined with real-time PCR and immunohistochemistry. Nitric oxide (NO) production was determined by Calorimetric Nitric Oxide Assay kit. Superoxide anion levels were detected with lucigenin-enhanced chemiluminescence assay and dihydroethidium (DHE) staining.', 'The endothelium-dependent vasorelaxation in response to bradykinin was significantly reduced in HIV Nef-treated porcine pulmonary artery rings in a concentration-dependent manner. In response to bradykinin (10(-8) mol/L), HIV Nef (10 ng/mL) significantly reduced vasorelaxation by 32% compared with untreated controls (P < 0.05). In addition, HIV Nef significantly decreased eNOS expression in the vessels and HPAECs. HIV Nef at 10 ng/mL significantly decreased NO production in HPAECs by 21% compared with controls (P < 0.05). Furthermore, HIV Nef significantly increased superoxide anion production in porcine pulmonary arteries and HPAECs compared with controls (P < 0.05). Consequently, Mn (III) tetrakis porphyrin, a superoxide dismutase mimic, effectively blocked HIV Nef-induced vasomotor dysfunction and superoxide anion production. The specificity of HIV Nef action was confirmed by anti-Nef antibody blocking and Nef heat inactivation.",
            "output": [
                "Does hIV Nef protein cause endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells?"
            ]
        },
        {
            "id": "task847-43614fb199534e17a91f538769cf2b3c",
            "input": "The present study examined the effects of intraportal infusion of L-arginine on ischemia/reperfusion injury (I/RI) in pig livers, by observing changes in the liver function, liver cell morphology, and changes in the mitochondrial ultrastructure.', 'The involvement of the nitric oxide (NO) pathway in the reperfusion-ischemic phenomenon is complex and not fully understood. Likewise, little is known about the possible benefit of intraportal infusion of L-arginine (substrate for the NO synthesis) on liver I/RI.', 'A pig model consisting of 90 min of hepatic ischemia and 180 min of reperfusion was employed. Eighteen female hybrid pigs were randomly divided into three groups: sham-operated, non-preconditioned, and pharmacologically preconditioned group (intraportal infusion of L-arginine 400 mg/kg) 10 min before being subjected to ischemia and reperfusion. Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), thiobarbituric acid reactive substances (TBARS), and the bile flow were measured. Liver biopsies were taken 180 min after reperfusion for histology, caspase-3 immunohistochemistry, and ultrastructural examination of mitochondria.', 'In the pharmacologically preconditioned group, we observed increased bile flow (P < 0.01) and improved serum AST levels (P < 0.01) relative to the non-preconditioned group. Serum concentrations of TBARS did not differ between the groups. Sinusoidal congestion (P = 0.02) was more evident in the non-preconditioned group than in the sham operated group. Infiltrating PMNs (P = 0.01) were more evident in the non-preconditioned group than in the sham and pharmacologically preconditioned group. The pharmacologically preconditioned group showed an approximately 2.5-fold decrease in caspase-3 activity relative to the non-preconditioned group (P < 0.01). Notably, damage to the mitochondrial ultrastructure in the pharmacologically preconditioned group was reduced relative to the other groups (P < 0.01).",
            "output": [
                "Does pharmacological preconditioning using intraportal infusion of L-arginine protect against hepatic ischemia reperfusion injury?"
            ]
        },
        {
            "id": "task847-13c126d5ec2049ea84d46639a5f2680c",
            "input": "Hepatitis B virus (HBV) infections are a matter of concern in hemodialysis units; occult HBV infections (serum HBsAg negative but HBV DNA positive) were demonstrated in this setting, and this involves further concerns regarding possible transmission and pathogenic consequences. This study aimed to investigate the prevalence and correlates of occult HBV infection in a group of patients with reference to a single hemodialysis unit in southeastern Italy.', 'We analyzed HBV serology and DNA (using a qualitative nested PCR) in 128 HBsAg-negative hemodialysis patients, and correlated the results obtained, with sex, age, hemodialysis duration and HCV seropositivity.', 'As a whole, occult HBV infection was demonstrated in 34/128 patients (26.6%); HBV DNA detection was more frequent when anti-HBcAg antibodies were detected in isolation (72%) than when associated with anti-HBsAg antibodies (31%). Among HCV-seropositive patients, occult HBV infection was observed in 66%, and among these as many as 14/15 patients (93%) who were HCV+/anti-HBcAg+ had serum HBV DNA detectable. On multivariate analysis, HCV seropositivity and the presence of anti-HBs were still respectively correlated to the presence and absence of occult HBV infection.",
            "output": [
                "Is occult HBV infection in hemodialysis setting marked by presence of isolated antibodies to HBcAg and HCV?"
            ]
        },
        {
            "id": "task847-4f87d2d52ed04944bbfebd988ec0620a",
            "input": "Several aspects of renoprotection by angiotensin-converting enzyme inhibitors (ACEi) in IgA nephropathy (IgAN) are poorly defined: factors affecting responsiveness, role of proteinuria components and histological lesions, and criteria to identify patients who may benefit from ACEi.', 'In an observational study of 140 IgAN patients (follow up 62 +/- 36 months), 73 untreated and 67 ACEitreated for 53 +/- 28 months, 9 baseline risk factors (RFs) (blood pressure, serum creatinine, proteinuria/day, fractional excretion of IgG [FEIgG] and alpha1-microglobulin, global and segmental [SS] glomerular sclerosis, tubulointerstitial damage and arteriolar hyalinosis [AH] score), each divided into 2 subgroups according to a cutoff with the highest sensitivity and specificity for progression, were evaluated for ability to predict renoprotection. Primary end point: end-stage renal disease (ESRD) and doubling of serum creatinine (sCr); secondary end point: increase >or=25% of sCr with last sCr >or=1.58 mg/dL; total progression: sum of end points.', 'Patients with RFs below cutoffs did not benefit from ACEi. All clinical and proteinuric and 2 histological RFs (SS, AH score) with values above cutoffs showed significant reduction of progression in ACEitreated vs. untreated patients; FEIgG showed the highest prediction of renoprotection: ESRD/sCrx2: 20% vs. 62% (p=0.0004); total progression: 40% vs. 85% (p=0.0003). By multivariate analysis, independent predictors of progression were FEIgG, sCr and no ACEi treatment. Proteinuria reduction from -100% to -30%, spontaneous or after ACEi treatment, did not affect progression in treated vs. untreated patients (19% vs. 13%, p=0.85). Patients with proteinuria increased or reduced <30% showed a reduction of total progression if ACEi-treated (15% vs. 77%, p=0.0002). Presence of 1 clinical or proteinuric RF above the cutoff may be a criterion to identify patients who may benefit from ACEi.",
            "output": [
                "Is fractional urinary excretion of IgG the most powerful predictor of renoprotection by ACE inhibitors in IgA nephropathy?"
            ]
        },
        {
            "id": "task847-3854cde0b34146e58f75ea04315312d1",
            "input": "A large proportion of interstitial fibroblasts actually originate from tubular epithelial cells via the epithelial-to-mesenchymal transition (EMT) in renal fibrogenesis. Transforming growth factor-beta1 (TGF-beta1) is capable of initiating and completing the entire EMT course. Bone morphogenetic protein-7 (BMP-7) is a member of the TGF-beta superfamily. Recent studies indicate that BMP-7 could reverse established renal fibrosis in mice, primarily through counteracting TGF-beta1-mediated EMT. Therefore, we tested the hypothesis that BMP-7 functions by antagonizing profibrogenic events that are induced by TGF-beta1 in cultured human renal proximal tubular epithelial (HK-2) cells.', 'Cultured HK-2 cells were treated with TGF-beta1 (3 ng/mL) or a combination of TGF-beta1 and BMP-7 (100-400 ng/mL) for 48 hours. Morphological changes were assessed by phase contrast microscopy. The expression of alpha-smooth muscle actin (alpha-SMA), E-cadherin, fibronectin, collagen I and connective tissue growth factor (CTGF) was analyzed by immunofluorescence, reverse transcriptase polymerase chain reaction and Western blotting.', 'Incubation of HK-2 cells with 3 ng/mL TGF-beta1 for 48 hours induced EMT, in association with decreased E-cadherin expression, increased alpha-SMA, fibronectin, collagen I and CTGF expression, and loss of epithelial morphology. BMP-7 inhibited all these effects in a dose-dependent manner. In addition, 200 ng/mL BMP-7 reversed TGF-beta1-induced EMT, in association with reexpression of endogenous E-cadherin.",
            "output": [
                "Does bMP-7 counteract TGF-beta1-induced epithelial-to-mesenchymal transition in human renal proximal tubular epithelial cells?"
            ]
        },
        {
            "id": "task847-2dc3ec519b474fd5be703841b0032175",
            "input": "Intrahepatic bile duct (IHBD) development begins with the differentiation of hepatoblasts into a single continuous biliary epithelial cell (BEC) layer, called the ductal plate. During ductal plate remodeling, tubular structures arise at distinct sites of the ductal plate, forming bile ducts that dilate into the biliary tree. Alagille syndrome patients, who suffer from bile duct paucity, carry Jagged1 and Notch2 mutations, indicating that Notch2 signaling is important for IHBD development. To clarify the role of Notch2 in BEC differentiation, tubulogenesis, and BEC survival, we developed a mouse model for conditional expression of activated Notch2 in the liver. We show that expression of the intracellular domain of Notch2 (Notch2ICD) differentiates hepatoblasts into BECs, which form additional bile ducts in periportal regions and ectopic ducts in lobular regions. Additional ducts in periportal regions are maintained into adulthood and connect to the biliary tight junction network, resulting in an increased number of bile ducts per portal tract. Remarkably, Notch2ICD-expressing ductal plate remnants were not eliminated during postnatal development, implicating Notch2 signaling in BEC survival. Ectopic ducts in lobular regions did not persist into adulthood, indicating that local signals in the portal environment are important for maintaining bile ducts.",
            "output": [
                "Does notch2 signaling promote biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice?"
            ]
        },
        {
            "id": "task847-f78bfe3f276c4681a4894fbdf124ab9a",
            "input": "In Parkinson's disease, striatal dopamine transporter (DAT) binding and cardiac sympathetic function are disturbed. In addition, heart rate (HR)-corrected cardiac repolarisation time (QTc interval), which is partly under autonomic control, is prolonged. Whether there is physiological coupling between striatal DAT binding and QTc time (QTc-DAT relation) is not known. The purpose of this study is to evaluate QTc-DAT relation in healthy young adults.\", \"Thirty-five participants (18 women, age 26.4+/-1.8 years; mean+/-SD) were studied with iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single photon emission tomography. Signal-averaged ECG was recorded at rest from each participant. QTc interval was computed with Bazett's correction and with the approach by Karjalainen, getting QTc and QTk intervals, respectively.\", 'Mean striatal DAT binding, as (striatum-cerebellum)/cerebellum, was 2.63+/-0.31. Mean HR, QT, QTc and QTk intervals were 66+/-9 bpm, 340+/-25 ms, 354+/-18 ms and 351+/-16 ms, respectively. HR-QT correlation was -0.63, P value of less than 0.001. HR was not related to striatal DAT binding. QTc-DAT and QTk-DAT relations were significant, r = -0.50, P = 0.004 and r = -0.59, P = 0.0002, respectively. In linear regression model, striatal DAT binding explained 35% of the variance of QTk interval (95% confidence interval: -46.9 to -13.0, P = 0.0002).",
            "output": [
                "Are cardiac repolarization and striatal dopamine transporter function interrelated?"
            ]
        },
        {
            "id": "task847-91dabfa0d5f94b00909a1e4baeccb10e",
            "input": "Hyponatremia has been shown to predict adverse outcome in congestive heart failure and pneumonia among other common clinical entities, but its significance in the general population is elusive.', 'The population-based Copenhagen Holter Study included 671 men and women aged 55 to 75 years with no history of cardiovascular disease, stroke, or cancer. Baseline evaluation included 48-hour ambulatory electrocardiogram monitoring, blood tests, and a questionnaire. Hyponatremia was defined as s-Na < or = 134 mEq/L or s-Na < or = 137 mEq/L according to previously accepted definitions. An adverse outcome was defined as deaths or myocardial infarction. Median follow-up was 6.3 years.', 'Fourteen subjects (2.1%, group A) had s-Na < or = 134 mEq/L, and 62 subjects (9.2%, group B) had s-Na < or = 137 mEq/L. No subject had s-Na < 129 mEq/L. An adverse outcome occurred in 43% of group A, 27% of group B, and 14% of subjects with s-Na >137 mEq/L (controls) (P < .002). Adjusted hazard ratio for adverse outcome was 3.56 (95% confidence interval [CI], 1.53-8.28, P < .005) in group A compared with controls and 2.21 (95% CI, 1.29-3.80, P < .005) in group B after controlling for age, gender, smoking, diabetes, low-density lipoprotein cholesterol, and blood pressure. The hazard ratios were robust for additional adjusting for variables showing univariate association to hyponatremia (ie, beta-blocker and diuretic use, heart rate variability, creatinine, C-reactive protein, and NT-pro brain natriuretic peptide). By excluding diuretic users (18% of subjects), the adjusted hazard ratio for adverse outcome was 8.00 (95% CI, 3.04-21.0, P < .0001) in group A and 3.17 (95% CI, 1.76-5.72, P = .0001) in group B compared with controls.",
            "output": [
                "Does mild hyponatremia carry a poor prognosis in community subjects?"
            ]
        },
        {
            "id": "task847-14ab3efad8534f79829913e39d0a2ed0",
            "input": "There is limited information on whether increased serum uric acid levels are independently associated with cardiovascular mortality in type 2 diabetes. We assessed the predictive role of serum uric acid levels on all-cause and cardiovascular mortality in a large cohort of type 2 diabetic individuals.', 'The cohort included 2,726 type 2 diabetic outpatients, who were followed for a mean period of 4.7 years. The independent association of serum uric acid levels with all-cause and cardiovascular mortality was assessed by Cox proportional hazards models and adjusted for conventional risk factors and several potential confounders.', 'During follow-up, 329 (12.1%) patients died, 44.1% (n = 145) of whom from cardiovascular causes. In univariate analysis, higher serum uric acid levels were significantly associated with increased risk of all-cause (hazard ratio 19 [95% CI 1.12-1.27], P < 0.001) and cardiovascular (1.25 [1.16-1.34], P < 0.001) mortality. After adjustment for age, sex, BMI, smoking, hypertension, dyslipidemia, diabetes duration, A1C, medication use (allopurinol or hypoglycemic, antihypertensive, lipid-lowering, and antiplatelet drugs), estimated glomerular filtration rate, and albuminuria, the association of serum uric acid with cardiovascular mortality remained statistically significant (1.27 [1.01-1.61], P = 0.046), whereas the association of serum uric acid with all-cause mortality did not.",
            "output": [
                "Do elevated serum uric acid concentrations independently predict cardiovascular mortality in type 2 diabetic patients?"
            ]
        },
        {
            "id": "task847-a58b074458174ec7835fc24bfc7b1c1c",
            "input": "This study evaluates whether depression is a risk factor for incident myocardial infarction (MI) in Department of Veterans Affairs (VA) patients with rheumatoid arthritis (RA) between 30 and 79 years of age.', 'We used a retrospective cohort study of 15,634 patients with RA. Diagnoses and sociodemographic data were obtained from VA administrative and pharmacy databases between fiscal years 1999 and 2006. Entry into the cohort required 2 years of patient time with no evidence of cardiovascular disease. Cox proportional hazard models with time-dependent covariates were computed to determine whether RA patients with depression as compared to RA patients without depression were at increased risk for MI during the maximum 6-year follow-up period.', 'Unadjusted analyses indicated depressed RA patients were 1.4 times more likely than nondepressed RA patients to have an MI during follow-up. These results remained significant (HR=1.4; 95% CI: 1.1-1.8) in the adjusted Cox proportional hazards model which included the effects of sociodemographics and known physical risks (e.g., diabetes) for MI.",
            "output": [
                "Does depression increase risk of incident myocardial infarction among Veterans Administration patients with rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-c7d9a022f1be4cb49ab611675003210e",
            "input": "The authors set out to analyze if a simple comprehensive geriatric assessment (CGA) could objectively identify elderly patients with diffuse large cell lymphoma (DLCL) who can be effectively treated with anthracycline-containing immunochemotherapy.', 'CGA was performed in 84 consecutive patients with DLCL aged >65 years and diagnosed at a single institution. Treatment with curative versus palliative intent was chosen according to clinical judgment. Cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisone (CHOP) or CHOP-like regimens were given to 62 (74%) patients. The outcome of patients was analyzed according to both the treatment received and the results of CGA.', 'According to CGA, 42 (50%) patients were classified as \"fit.\" They were younger (P < .0001) and had less frequent systemic symptoms (P = .03). These patients received curative treatment by clinical judgment. Their response rate (92.5% vs 48.8%; P < .0001) and median survival (not reached vs 8 months; P < .0001) were significantly better than those of 42 patients considered \"unfit\" by CGA. Among unfit patients, 20 had actually received curative and 22 palliative therapy. These subgroups did not differ in any geriatric or lymphoma-related characteristic. Their outcome was similar irrespectively of the type of treatment received (median survival, 8 vs 7 months; P = nonsignificant). Lymphoma rather than toxicity was the main cause of failure/death also among unfit patients treated aggressively.",
            "output": [
                "Is a comprehensive geriatric assessment more effective than clinical judgment to identify elderly diffuse large cell lymphoma patients who benefit from aggressive therapy?"
            ]
        },
        {
            "id": "task847-7625b9b2742e4ec3b9603ec003641bda",
            "input": "A severe and challenging complication in the treatment of hemophilia A is the development of inhibiting antibodies (inhibitors) directed towards factor VIII (FVIII). Inhibitors aggravate bleeding complications, disabilities and costs. The etiology of inhibitor development is incompletely understood.', 'In a large cohort study in patients with mild/moderate hemophilia A we evaluated the role of genotype and intensive FVIII exposure in inhibitor development.', 'Longitudinal clinical data from 138 mild/moderate hemophilia A patients were retrospectively collected from 1 January 1980 to 1 January 2008 and analyzed by multivariate analysis using Poisson regression.', 'Genotyping demonstrated the Arg593Cys missense mutation in 52 (38%) patients; the remaining 86 patients had 26 other missense mutations. Sixty-three (46%) patients received intensive FVIII concentrate administration, 41 of them for surgery. Ten patients (7%) developed inhibitors, eight of them carrying the Arg593Cys mutation. Compared with the other patients, those with the Arg593Cys mutation had a 10-fold increased risk of developing inhibitors (RR 10; 95% CI, 0.9-119).The other two inhibitor patients had the newly detected mutations Pro1761Gln and Glu2228Asp. In both these patients and in five patients with genotype Arg593Cys, inhibitors developed after intensive peri-operative use of FVIII concentrate (RR 186; 95% CI, 25-1403). In five of the 10 inhibitor patients FVIII was administered by continuous infusion during surgery (RR 13; 95% CI, 1.9-86).",
            "output": [
                "Are intensive peri-operative use of factor VIII and the Arg593 -- > Cys mutation risk factors for inhibitor development in mild/moderate hemophilia A?"
            ]
        },
        {
            "id": "task847-9d4986bd2cc24a99a051f8aa681a4cf2",
            "input": "Microparticles (MPs), small vesicles shed from stimulated cells, permit cross-talk between cells within a particular environment. Their composition is thought to reflect their cell of origin, and differs according to whether they are produced by stimulation or by apoptosis. Whether MP properties vary according to stimulus is not yet known.', 'We studied the characteristics of MPs produced from monocytic THP-1 cells upon stimulation with lipopolysaccharide or a soluble P-selectin chimera, using proteomics, flow cytometry, western blotting, and electron microscopy.', 'Utilizing a novel criterion of calcein-AM staining to define MPs, we found that MP populations were similar with respect to size, presence and organization of cytoskeleton, and expression of certain antigens. The MPs shared the same level of procoagulant activity. We found that MPs also have distinct characteristics, depending on stimuli. These include differences in phosphatidylserine expression and expression of proteins from specific subcellular locations such as the mitochondria, and of unique antigens such as leukocyte-associated immunoglobin-like-receptor (LAIR)-1, which was found only upon stimulation with the soluble P-selectin chimera.",
            "output": [
                "Does differential stimulation of monocytic cells result in distinct populations of microparticles?"
            ]
        },
        {
            "id": "task847-a4ffac39653049ca9853a29a4f48d341",
            "input": "Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task.', 'For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [(11)C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus.",
            "output": [
                "Do dopamine transporters in striatum correlate with deactivation in the default mode network during visuospatial attention?"
            ]
        },
        {
            "id": "task847-538ee25633cd4a618b7d7043c91e9dfc",
            "input": "To determine whether during the initial phase of head and neck cooling, jugular bulb temperature (Tjb; which may reflect brain temperature) is lower than esophageal temperature (Tes).', 'To compare Tes and Tjb, patients received head or head and neck cooling after cardiac arrest.', 'The first series with head cooling (n = 5; mean age 54 with a range of 41-62 years; 1 female and 4 males; mean body weight 80 kg with a range of 70-85 kg) showed a mean difference of 0.22 degrees C (95% CI, -1.14 to 0.70; P = .55; limits of agreement, -3.17 to 2.73) between Tes and Tjb over 12 hours. For the second series, with head and neck cooling (n = 6, mean age 65 with a range of 56-76 years; 3 females and 3 males; mean body weight 75 kg with a range of 65-91 kg), Tjb was lower than Tes with a difference of 0.60 degrees C (95% CI, 0.22 to 0.99; P = .01; limits of agreement, -3.10 to 4.30). During the first 3 hours, Tjb decreased faster than Tes (1.1 degrees C/h [95% CI, 0.4 to 1.8; P < .01]).",
            "output": [
                "Does head and neck cooling after cardiac arrest result in lower jugular bulb than esophageal temperature?"
            ]
        },
        {
            "id": "task847-4840446492144730ab3d0f4d476bfc82",
            "input": "There are safety concerns about TASER conducted electrical weapon (CEW) use on humans, and there have been media reports of adverse human outcomes after CEW exposure. Conducted electrical weapons are often used on physically exhausted subjects. A single CEW application of a CEW is generally accepted to be 5 seconds of exposure. Some exposures in reality involve more than 5 seconds. We sought to determine if a prolonged (15 seconds) CEW exposure on exhausted humans caused acidosis, hyperkalemia, serum lactate change, or troponin change.', 'This was a prospective study of generally healthy human volunteers. Medical histories and baseline serum values were obtained, and several of the volunteers did have acute or chronic medical problems. Subjects underwent an exercise protocol until subjective exhaustion. Exhaustion was defined by the volunteer no longer being able to perform the exercise at a given pace. Blood was drawn immediately (defined as within 20 seconds) after exercise and was immediately followed by a 15-second CEW exposure. Blood was drawn immediately after exposure and again at 16 to 24 hours after exposure. Blood was analyzed for pH, pco(2), potassium, lactate, and troponin. Data were compared using Wilcoxon signed rank tests.', 'There were 38 subjects enrolled with an average age of 39 years. The following health conditions were reported among the volunteers: hypertension (2), gastritis/reflux (2), active respiratory tract infections (3), asthma (2), chronic muscular pain conditions (4), pituitary adenoma (1) and glaucoma (1). Sixteen volunteers reported use of prescription medication at the time of their participation. The median initial pH of 7.38 (interquartile range [IQR], 7.35-7.40) decreased to 7.23 (IQR, 7.19-7.31) immediately after exercise. Immediately after exposure, median pH was 7.22 (IQR, 7.18-7.25). It was 7.39 (IQR, 7.37-7.43) at 24 hours. The pCO2 increased from 46.3 (IQR, 43.0-54.5) to 57.4 (IQR, 49.9-67.7) immediately after exercise, decreased to 51.3 (IQR, 44.4-65.0) immediately after exposure, and was 46.3 (IQR, 42.7-51.7) at 24 hours. Lactate increased from a median of 1.65 (IQR, 1.14-2.55) to 8.39 (IQR, 6.98-11.66) immediately after exercise, increased to 9.85 (IQR, 7.70-12.87) immediately after exposure, and was 1.02 (IQR, 0.91-1.57) at 24 hours. Serum potassium increased from 3.9 (IQR, 3.8-4.4) to 4.2 (IQR, 4.0-4.9) immediately after exercise, decreased to 3.8 (IQR, 3.7-4.4) immediately after exposure, and was 4.1 (IQR, 3.9-4.6) at 24 hours. No troponin elevations were detected.",
            "output": [
                "Does prolonged TASER use on exhausted humans worsen markers of acidosis?"
            ]
        },
        {
            "id": "task847-e0ac705bb23c431d96966150e7e57bb2",
            "input": "Phosphatidylinositol 3-OH kinase (PI3K) has a long-recognized role in beta-cell mass regulation and gene transcription and is implicated in the modulation of insulin secretion. The role of nontyrosine kinase receptor-activated PI3K isoforms is largely unexplored. We therefore investigated the role of the G-protein-coupled PI3Kgamma and its catalytic subunit p110gamma in the regulation of insulin granule recruitment and exocytosis.', 'The expression of p110gamma was knocked down by small-interfering RNA, and p110gamma activity was selectively inhibited with AS605240 (40 nmol/l). Exocytosis and granule recruitment was monitored by islet perifusion, whole-cell capacitance, total internal reflection fluorescence microscopy, and electron microscopy in INS-1 and human beta-cells. Cortical F-actin was examined in INS-1 cells and human islets and in mouse beta-cells lacking the phosphatase and tensin homolog (PTEN).', 'Knockdown or inhibition of p110gamma markedly blunted depolarization-induced insulin secretion and exocytosis and ablated the exocytotic response to direct Ca(2+) infusion. This resulted from reduced granule localization to the plasma membrane and was associated with increased cortical F-actin. Inhibition of p110gamma had no effect on F-actin in beta-cells lacking PTEN. Finally, the effect of p110gamma inhibition on granule localization and exocytosis could be rapidly reversed by agents that promote actin depolymerization.",
            "output": [
                "Is insulin granule recruitment and exocytosis dependent on p110gamma in insulinoma and human beta-cells?"
            ]
        },
        {
            "id": "task847-f0e6bed0cfd243f785893010f746f0bd",
            "input": "Increased triglyceride (TG) occurs in patients with acute coronary syndrome (ACS), and apolipoprotein AV (apoAV) has been shown to lower TG levels. In the present study, we investigated plasma apoAV level and its relationship with TG and C-reactive protein (CRP) in ACS patients.', 'A total of 459 subjects were recruited and categorized into control group (n = 116), stable angina (SA) group (n = 115), unstable angina group (n = 116) and acute myocardial infarction group (n = 112). Plasma apoAV level was measured by a sandwich ELISA assay.', 'Compared with controls ((100.27 +/- 22.44) ng/ml), plasma apoAV was decreased in SA patients ((76.54 +/- 16.91) ng/ml) but increased in patients with unstable angina ((330.89 +/- 66.48) ng/ml, P < 0.05) or acute myocardial infarction ((368.66 +/- 60.53) ng/ml, P < 0.05). Inverse correlations between apoAV and TG were observed in the control or stable angina groups (r = -0.573 or -0.603, respectively, P < 0.001), whereas positive correlations were observed in the patients with unstable angina or acute myocardial infarction (r = 0.696 or 0.690, respectively, P < 0.001). Furthermore, a positive relationship between apoAV and CRP was observed in the ACS patients but not in the non-ACS subjects.",
            "output": [
                "Is elevated plasma apolipoprotein AV in acute coronary syndrome positively correlated with triglyceride and C-reactive protein?"
            ]
        },
        {
            "id": "task847-d1fc3d757f2242b3858c414ba3253085",
            "input": "Adenoid cystic carcinomas are rare tumors with an indolent clinical course, but frequent local relapses. The identification of tumors with a higher relapse risk seems to be interesting. Hence we investigated parameters of glucose metabolism, which were found associated with poor prognosis in other malignancies.', 'Specimen of 29 patients were investigated immunohistochemically with antibodies against p-AKT, TKTL-1 (transketolase-like 1), M2PK (M2 pyruvate kinase), and GLUT-1. Proliferation was investigated by staining with Ki67. The tumors were located at the major or minor salivary glands. Only the typical cribriform subtype was investigated. The initial tumor stage was pT1 or pT2.', 'Expression of p-AKT was significantly (P = 0.036) associated with a higher relapse risk in multivariate analysis. Low expression of M2PK was non-significantly (P = 0.065) predictive for a higher risk. TKTL-1 and GLUT-1 were expressed in the majority of cases, albeit not associated with relapse risk.",
            "output": [
                "Does expression of p-AKT characterize adenoid cystic carcinomas of head and neck with a higher risk for tumor relapses?"
            ]
        },
        {
            "id": "task847-729e1586681e4e2ca47e4d3dbb256c8c",
            "input": "Although attention to human rights in Indonesia has been improving over the past decade, the human rights situation of persons with mental disorders is still far from satisfactory. The purpose of this paper is to examine the legal framework for protection of human rights of persons with mental disorder and the extent to which Indonesia's international obligations concerning the right to health are being met.\", 'We examined the Indonesian constitution, Indonesian laws relevant to the right to health, the structure and operation of the National Human Rights Commission, and what is known about violations of the human rights of persons with mental illness from research and the media.', 'The focus of the Indonesian Constitution on rights pre-dated the Universal Declaration, Indonesia has ratified relevant international covenants and domestic law provides an adequate legal framework for human rights protections. However, human rights abuses persist, are widespread, and go essentially unremarked and unchallenged. The National Human Rights Commission has only recently become engaged in the issue of protection of the rights of persons with mental illness.",
            "output": [
                "Is human rights of persons with mental illness in Indonesia : more than legislation needed?"
            ]
        },
        {
            "id": "task847-01edbfc609c44cd4a5ba188d38b001be",
            "input": "A disintegrin and metalloprotease 12 (ADAM12) has multiple domains and functions, and it plays important roles in the development of cancer. We conducted a retrospective study to determine whether the expression of the membrane type of ADAM12 (ADAM12-L) could be a prognostic factor in resected pathological (p-) stage I lung adenocarcinoma.', 'ADAM12-L mRNA expression was quantified by a reverse-transcription polymerase chain reaction in tissue samples from 84 completely resected p-stage I lung adenocarcinoma patients. The patients were divided into ADAM12-L-Low and ADAM12-L-High groups, and correlations with clinicopathologic features were obtained.', 'Five-year survival rates of the ADAM12-L-Low and ADAM12-L-High groups were 95.1% and 71.9%, respectively. The postoperative prognosis for the ADAM12-L-High group was significantly poorer than for the ADAM12-L-Low group (P = 0.006). Multivariate analysis confirmed that high expression of ADAM12-L was an independent factor for poor prognosis (P = 0.007, hazard ratio 8.288). The ADAM12-L-High group was less differentiated and had a significantly higher rate of cancer recurrence.",
            "output": [
                "Is a disintegrin and metalloprotease 12 ( ADAM12 ) a prognostic factor in resected pathological stage I lung adenocarcinoma?"
            ]
        },
        {
            "id": "task847-e5d06c29084242fbbc4ddd87365307d9",
            "input": "Protein Z is a glycoprotein that acts as a co-factor for the inhibition of activated coagulation factor X. Protein Z circulating in abnormal levels has been associated with increased risk for acute ischemic events. Non-arteritic Anterior Ischemic Optic Neuropathy (N-AION) is caused by acute ischemic infarction of the optic nerve head, supplied by the posterior ciliary arteries.', 'The aim was to investigate whether there is an association between N-AION and plasma protein Z levels.', 'Twenty-six cases of confirmed N-AION and fifty-two controls were included in the study group. Protein Z was estimated in thawed citrate plasma on both N-AION cases and controls by an enzyme immunoassay. The imprecision of the estimation was satisfactory (CV = 4, 6%).', \"The controls' protein Z values distributed within a range 340 to 4200 ng/ml (median = 1420, mean = 1673, SD = 1040 ng/ml). Patients' protein Z values distributed within a range 420 to 3600 ng/ml (median = 1030, mean = 1520, SD = 939 ng/ml). There was no statistical difference between the two distributions (Independent t-test, p=0.529).",
            "output": [
                "Are protein Z Plasma Levels Elevated in Patients with Non-Arteritic Anterior Ischemic Optic Neuropathy?"
            ]
        },
        {
            "id": "task847-00f0c1f5fe35478384ec73afd817ac1c",
            "input": "To evaluate the use of fluid-attenuated inversion recovery (FLAIR) imaging as surrogate marker of lesion age within the first 6 hours of ischemic stroke.', 'e analyzed FLAIR and diffusion-weighted imaging (DWI) sequences performed within 6 hours of symptom onset in 120 consecutive patients with ischemic stroke with known symptom onset. The visibility of acute ischemic lesions on FLAIR images was judged in two steps (on FLAIR alone and with knowledge of DWI) and compared with DWI.', 'egative FLAIR in the case of positive DWI allocated ischemic lesions to a time window 3 hours or less with a high specificity (0.93) and a high positive predictive value (0.94), whereas sensitivity (0.48) and negative predictive value (0.43) were low. Lesion visibility on FLAIR images alone (35.6%) and with knowledge of DWI (62.5%) was lower than on DWI (97.1%). The sensitivity of FLAIR increased with increasing time from symptom onset from 27.0/50.0% <or= 3 hours to 56.7/93.3% after 3 to 6 hours (FLAIR alone/with knowledge of DWI). Multivariate regression analysis spotted longer time from symptom onset and larger size of the ischemic lesion as independent predictors of lesion visibility on FLAIR images.",
            "output": [
                "Does negative fluid-attenuated inversion recovery imaging identify acute ischemic stroke at 3 hours or less?"
            ]
        },
        {
            "id": "task847-8562bf5c5b444ea0b1a4ce9e7b1a3008",
            "input": "Several immune suppressive mechanisms that evade the host immune response have been described in patients with hepatocellular carcinoma (HCC); one of these mechanisms is expansion of myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to inhibit T cell responses in tumor-bearing mice, but little is known about these cells in humans. Here, we have analyzed and characterized the effect of MDSCs on the innate immune system, in particular, their interaction with natural killer (NK) cells in patients with HCC. MDSCs from patients with HCC inhibited autologous NK cell cytotoxicity and cytokine secretion when cultured together in vitro. This suppression was dependent on cell contact, but did not rely on the arginase activity of MDSCs, which is a hallmark function of these cells. However, MDSC-mediated inhibition of NK cell function was dependent mainly on the NKp30 on NK cells.",
            "output": [
                "Do myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor?"
            ]
        },
        {
            "id": "task847-ee3ea37e4fd240ec9a2a02eeaf8ddff4",
            "input": "Oxidized Lp(a) [ox-Lp(a)] has been reported to play more potent roles than native Lp(a) in atherosclerosis. We investigated the distribution characteristics of plasma ox-Lp(a) and Lp(a) immune complex [Lp(a)-IC] levels in newborns and children.', 'Plasma ox-Lp(a) and Lp(a)-IC levels were measured in 747 children and 30 cord blood by ELISAs.', 'The mean levels of Lp(a), ox-Lp(a) and Lp(a)-IC were much lower in newborns than in children (P<0.001), and increased rapidly to that in children after birth. The distributions of Lp(a), ox-Lp(a) and Lp(a)-IC were skewed toward low values in children, no difference of their levels was found in each of the 13year groups. The levels of ox-Lp(a) correlated positively with total and LDL cholesterol, Lp(a) and Lp(a)-IC; Lp(a)-IC correlated positively with sex, total and LDL cholesterol, Lp(a) and ox-Lp(a), respectively. Multiple linear regression analysis showed Lp(a) and Lp(a)-IC accounted for 42% of the variation in ox-Lp(a) levels, and ox-Lp(a) accounted for 30% of that in Lp(a)-IC.",
            "output": [
                "Are plasma oxidized lipoprotein ( a ) and its immune complexes present in newborns and children?"
            ]
        },
        {
            "id": "task847-30814522ee104acaa1e1ed49f22f9518",
            "input": "High mobility group box 1 (HMGB1) protein has been identified as a novel pro-inflammatory cytokine in coronary artery disease (CAD). We investigated the relationship between serum HMGB1 level and the severity of coronary artery stenosis.', 'Serum HMGB1 concentration in patients was measured by ELISA. All patients underwent coronary angiography and were assigned into groups according to the quartile of HMGB1 level.', 'HMGB1 level in USAP group was higher than that in control and SAP group. HMGB1 level in SAP group was higher than that in control group (p<0.05). Gensini scores in the highest quartile group (group IV), group III and group II were all significantly higher than that in the lowest quartile group (group I). There was significant correlation between angiographic Gensini score and serum level of HMGB1 (r=0.710, p<0.05). However, in subgroup analysis, we found that serum HMGB1 level was only correlated with angiographic Gensini score in SAP patients (r=0.786, p<0.05), but not USAP patients.",
            "output": [
                "Is increased serum HMGB1 related to the severity of coronary artery stenosis?"
            ]
        },
        {
            "id": "task847-11bd19d8122648bba0eb79a2658db7cc",
            "input": "The underlying genetic factors for the development and progression of hepatocellular carcinoma (HCC) are largely unknown. TNFalpha is a well characterized inflammatory mediator and is implicated in the development of HCC. We investigated TNFalpha polymorphisms for association with HCC.', 'The study population consisted of 227 HCC patients and 365 age and sex matched Korean controls. TNFalpha polymorphisms (G-238A, C-857T, and C-863A) were genotyped using pyrosequencing analysis. TNFalpha levels in patients with HCC were determined by enzyme linked immunosorbent assay (ELISA). Logistic regression analysis was used to determine the association with HCC and haplotype was calculated using EH program.', 'Of three TNFalpha polymorphisms investigated in our study, C-863A did not correlate with HCC. However, both G-238A and C-857T were found to be significantly associated with HCC. TNFalpha -238A allele was more frequent in HCC patients than in control [P=0.012; odds ratio (OR), 1.89; 95% confidence interval (CI), 1.14-3.13]. TNFalpha -857T was significantly associated with HCC patients (P=0.001; OR, 1.63; 95% CI, 1.21-2.19). Haplotype analysis revealed that the GTC haplotype (G-238A, C-857T, C-863A) was a risk marker for HCC (P=0.0021). Serum TNFalpha level was significantly increased in HCC patients with CT+TT genotype for TNFalpha -857 (P=0.018).",
            "output": [
                "Is tNFalpha promoter polymorphism a risk factor for susceptibility in hepatocellular carcinoma in Korean population?"
            ]
        },
        {
            "id": "task847-36bee612634b4511b93f3c3bed018c80",
            "input": "To determine whether the ingestion of a herbal supplement called Rhodiola-Gingko Capsule (RGC) would enhance the endurance performance of healthy volunteers and change relevant hormones in a favorable manner.', 'Seventy healthy male volunteers (age ranges from 18 to 22 years old) were randomly assigned to RGC group (35 cases, each capsule containing 270 mg herbal extracts, 4 capsules per day) or placebo group (35 cases, equivalent placebo preparation) for 7 weeks using computer produced digital random method. The endurance performance, serum testosterone and cortisol levels were measured at the baseline and the endpoint.', 'Sixty-seven subjects (34 in the RGC group and 33 in the placebo group) completed a 7-week treatment. The RGC group displayed a significantly greater baseline-to endpoint increase in maximal oxygen uptake (VO(2max)) than placebo group in both absolute (P=0.020) and relative values (P=0.023). At the endpoint, the serum cortisol level was unchanged in the RGC group compared with the baseline, but it was significantly elevated in the placebo group (P<0.05). The endpoint ratio of testosterone to cortisol, a surrogate for overtraining and fatigue in endurance exercises, was also indifferent compared with the baseline in the RGC group, but significantly decreased in the placebo group (P<0.05).",
            "output": [
                "Does dietary supplement with a combination of Rhodiola crenulata and Ginkgo biloba enhance the endurance performance in healthy volunteers?"
            ]
        },
        {
            "id": "task847-d983bed24d7b40b585c1cbea8d006067",
            "input": "To probe into an new methods preserving parathyroid gland of patients with thyroid carcinoma.', 'Thirty-six patients with thyroid carcinoma that primary treated were random divided into two groups: trial group and control group. Emulsion of activated-carbon particles was injected into the thyroid gland of trial group patients. After thirty minutes, central compartment dissection was performed in the all patients. The black stained tissue in the dissection specimen of trial group was separated. Total lymph node, metastasis lymph node and parathyroid gland in the black stained tissue, and non-black stained tissue in the central compartment dissection specimen of trial group and central compartment dissection specimen of control group were counted respectively.', 'Nineteen and twenty central compartment dissection was performed in trial group and control group respectively. There are 177 lymph nodes included 83 metastasis lymph nodes in the black-stained tissue of central compartment dissection specimen of trial group. No parathyroid gland was found in the black-stained tissue. Nine lymph nodes included 2 metastasis lymph nodes and 7 parathyroid glands were found in the non-black stained tissue of central compartment dissection specimen of trial group. There were 124 lymph nodes included 80 metastasis lymph nodes and 8 parathyroid glands in central compartment dissection specimen of control group. There are statistic difference between the amount of lymph node in black stain tissue and that of control group (t = 0.340, P = 0.003). Rate of staining lymph node were 95.2 percent.",
            "output": [
                "Are [ Parathyroid glands differentiated from lymph node by activated-carbon particles ]?"
            ]
        },
        {
            "id": "task847-0045a962e9ff4b9f87f191a6444fc462",
            "input": "In some subjects with suspected asthma who have normal spirometry, administration of bronchodilators (BD) improves expiratory flow rates. The predictive value of this phenomenon in adults is not known.', 'To evaluate the predictive value of the response to BD for bronchial hyper-responsiveness (BHR) using the metacholine challenge test (MCT). Patients and methods. The study population included 62 non-smoking adult patients (41.9% women) 29.5 +/- 15.5 years of age (range 18-64 years) with suspected asthma with normal spirometry that underwent MCT within 1 week. The response to BD (200 mu g inhaled salbutamol) was compared between subjects with positive and negative MCT using cutoff levels of provocative concentrations of metacholine causing a 20% decrease in forced expiratory volume in 1 second (FEV(1)) (PC(20)) of 4 and 8 mg/mL.', 'Mean (+/- SD) baseline FEV(1) was 87.8 +/- 12% of predicted. After BD administration the mean FEV(1) increased by 4.3 +/- 3.9%. The prevalence of BHR was 17.7% and 25.8% for PC(20) for PC(20) of 4 mg/mL and 8 mg/mL, respectively. The post-BD FEV(1) increment for subjects with positive and negative MCT tests was 3.9% +/- 3.3% versus 4.4% +/- 4.1%, respectively; p = 0.89, using cutoff of 4 mg/mL. The corresponding figures for cutoff of 8 mg/ml were 4.3% +/- 3.1% vs. 4.3% +/- 4.2%, respectively; p = 0.8465. There was no correlation between post-BD FEV(1) increment and PC(20) values in patients with positive MCT test for the above-mentioned cutoff levels (correlation coefficient r = 0.1645, p = 0.6289; and r = 0.2417, p = 0.4051, respectively).",
            "output": [
                "Is the response to bronchodilators in adults predictive of bronchial-hyperreactivity?"
            ]
        },
        {
            "id": "task847-eb0f0ae6a0f84e42871d2dbb5e66e76a",
            "input": "Aggrecanase cleavage at the 392Glu-393Ala bond in the interglobular domain (IGD) of aggrecan, releasing N-terminal 393ARGS fragments, is an early key event in arthritis and joint injuries. Here, we use a quantitative immunoassay of aggrecan ARGS neoepitope fragments in human synovial fluid to determine if this cleavage-site specific method better identifies joint pathology than previously available less specific aggrecan assays.', 'Synovial fluid (SF) from 26 people with healthy knees (reference) and 269 patients were analyzed in a cross-sectional study. Patient groups were acute inflammatory arthritis, acute knee injury, chronic knee injury and knee osteoarthritis (OA). Aggrecan ARGS fragments were assayed by ELISA using the monoclonal antibody OA-1. Total aggrecan content was analyzed by an ELISA using the monoclonal antibody 1-F21, and sulfated glycosaminoglycan by Alcian blue precipitation.', 'Aggrecan ARGS fragment concentrations in all groups differed from the reference group (P < 0.001). The acute inflammatory arthritis group had the highest median level, 177-fold greater than that of the reference group. Median levels (in pmol ARGS/ml SF) were: reference 0.5, acute inflammatory arthritis 88.5, acute knee injury 53.9, chronic knee injury 0.5 and OA 4.6. In contrast, aggrecan and sulfated glycosaminoglycan concentrations varied much less between groups, and only acute inflammatory arthritis and acute knee injury were found to have a two-fold increase in median levels compared to the reference.",
            "output": [
                "Is synovial fluid level of aggrecan ARGS fragments a more sensitive marker of joint disease than glycosaminoglycan or aggrecan levels : a cross-sectional study?"
            ]
        },
        {
            "id": "task847-7d66ffb195df4c9bab5b17be62e0ba80",
            "input": "To determine whether follicle curetting at the time of oocyte retrieval increases oocyte yield.', 'Retrospective review of all patients who underwent oocyte retrieval from July 1, 2003 to June 30, 2005.', 'Number of oocytes retrieved.', 'retrieval time, number of cryopreserved embryos, pregnancy rates, and incidence of ovarian hyperstimulation syndrome.', 'There were no differences in patient demographics, antral follicle count, cycle stimulation characteristics, fertilization rates, embryo quantity or quality, embryo cryopreservation rates, clinical pregnancy rates, live birth rates, or ovarian hyperstimulation syndrome between the groups. Retrievals that utilized curetting took three minutes longer. Follicle curetting significantly increased the number of oocytes retrieved, 13.9 +/- 0.6 compared to 11.4 +/- 0.6 oocytes without curetting (P = 0.003). The quantity of mature oocytes was also increased with curetting (10.3 +/- 0.5 versus 8.4 +/- 0.5, P = 0.006).",
            "output": [
                "Does follicle curetting at the time of oocyte retrieval increase the oocyte yield?"
            ]
        },
        {
            "id": "task847-0d0152e0081b443796d67e30406b7c76",
            "input": "Interaction of macrophages with aggregated matrix-anchored lipoprotein deposits is an important initial step in atherogenesis. Aggregated lipoproteins require different cellular uptake processes than those used for endocytosis of monomeric lipoproteins. In this study, we tested the hypothesis that engagement of aggregated LDL (agLDL) by macrophages could lead to local increases in free cholesterol levels and that these increases in free cholesterol regulate signals that control cellular actin.', 'AgLDL resides for prolonged periods in surface-connected compartments. Although agLDL is still extracellular, we demonstrate that an increase in free cholesterol occurs at sites of contact between agLDL and cells because of hydrolysis of agLDL-derived cholesteryl ester. This increase in free cholesterol causes enhanced actin polymerization around the agLDL. Inhibition of cholesteryl ester hydrolysis results in decreased actin polymerization.",
            "output": [
                "Does aggregated LDL in contact with macrophages induce local increases in free cholesterol levels that regulate local actin polymerization?"
            ]
        },
        {
            "id": "task847-091f4178caeb4dcb9d6d80499bfc0ee7",
            "input": "Increased serum hepcidin has been reported in patients receiving chronic hemodialysis, and hypothesized to contribute to the alterations of iron metabolism of end-stage renal disease. However, no quantitative assessment is available to date; the clinical determinants are still under definition; and the role of genetic factors, namely HFE mutations, has not yet been evaluated. The aim of this study was to quantitatively assess serum hepcidin-25 in hemodialysis patients versus controls, and analyze the relationship between hepcidin, iron indices, HFE genotype, and erythropoietic parameters.', 'Sixty-five hemodialysis patients and 57 healthy controls were considered. Hepcidin-25 was evaluated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, HFE genotype by restriction analysis.', 'Serum hepcidin-25 was higher in hemodialysis patients compared with controls. In patients, hepcidin-25 correlated positively with ferritin and C reactive protein, and negatively with serum iron after adjustment for confounders. Hepcidin/ferritin ratio was lower in patients with (n = 25) than in those without (n = 40) HFE mutations. At multivariate analysis, hepcidin-25 was independently associated with ferritin and HFE status. In a subgroup of 22 \"stable\" patients, i.e., with Hb levels on target, normal CRP levels, and absence of complications for at least 1 yr, hepcidin-25 was negatively correlated with Hb levels independently of confounders.",
            "output": [
                "Do hFE mutations modulate the effect of iron on serum hepcidin-25 in chronic hemodialysis patients?"
            ]
        },
        {
            "id": "task847-12b0a0801dda43b8930887dbe3e35861",
            "input": "The FAS/FASLG system has been proposed to play a key role in germ cell apoptosis. To elucidate the role of the genetic variants of cell death pathway genes in male infertility, we genotyped the polymorphisms of FAS, FASLG and caspase-8 (CASP8) genes and evaluated their effects on sperm apoptosis and semen quality in infertile men.', 'The genotypes of FAS, FASLG and CASP8 were determined in 620 infertile men. Sperm apoptosis rates were measured by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end labelling (TUNEL) assay, and the semen quality analysis was performed using computer assisted sperm analysis.', 'We found that polymorphisms of FAS-670A/G (rs1800682: A>G) and CASP8-652 6N ins/del (rs3834129: -/CTTACT) were associated with sperm apoptosis and semen quality. Individuals with FAS-670GG showed low apoptosis rate and decreased sperm concentration, compared with the FAS-670AA genotype. Similarly, in comparison with the CASP8-652 6N ins/ins genotype, the CASP8-652 6N (ins/del+del/del) genotypes also showed significantly decreased sperm apoptosis rate and poor sperm motility. Other polymorphisms investigated did not appear to affect sperm apoptosis and semen quality.",
            "output": [
                "Are polymorphisms in cell death pathway genes associated with altered sperm apoptosis and poor semen quality?"
            ]
        },
        {
            "id": "task847-65ec41f23de34eadbfd2f57a9448ce50",
            "input": "Epidermal phenolic compounds (mainly flavonoids) constitute a vital screen that protects the leaf from damage by natural ultraviolet (UV) radiation. The effectiveness of epidermal UV-screening depends on leaf anatomy, the content of UV-screening compounds and their spatial uniformity over the leaf area. To investigate in vivo the spatial pattern of the epidermal UV-screen during leaf development, a fluorescence imaging method was developed to map the epidermal UV-absorbance at a microscopic scale. This study was done on oak (Quercus petraea) leaves that were used as a model of woody dicotyledonous leaves.', 'The leaf development of 2-year-old trees, grown outdoors, was monitored, at a macroscopic scale, by in vivo measurements of chlorophyll content per unit area and epidermal UV-absorbance using two optical leaf-clip meters. The distribution of pigments within leaves was assessed in vivo spectroscopically. The microscopic images of UV-induced fluorescence and UV-absorbance acquired in vivo during leaf development were interpreted from spectral characteristics of leaves.', 'At a macroscopic scale, epidermal UV-absorbance was high on the upper leaf side during leaf development, while it increased on the lower leaf side during leaf expansion and reached the adaxial value at maturity. At a microscopic scale, in immature leaves, for both leaf sides, the spatial distribution of epidermal UV-absorbance was heterogeneous, with a pattern depending on the flavonoid content of vacuoles in developing epidermal cells. At maturity, epidermal UV-absorbance was uniform.",
            "output": [
                "Does developmental changes in spatial distribution of in vivo fluorescence and epidermal UV absorbance over Quercus petraea leave?"
            ]
        },
        {
            "id": "task847-d8b4682f00a14c7aa75e4dd27a1850c3",
            "input": "It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown.', \"Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016).",
            "output": [
                "Do low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use?"
            ]
        },
        {
            "id": "task847-47233def28eb45ed9db7966a92378c2b",
            "input": "The purpose of this study was to assess the therapeutic efficacy of oral versus intravaginal voriconazole and compare it with fluconazole for the treatment of experimental vaginitis caused by a fluconazole-resistant Candida albicans isolate.', 'Mice were treated with voriconazole at 5, 10 and 20 mg/kg once a day and 20 mg/kg twice a day or with fluconazole at 20 mg/kg once or twice a day orally. Intravaginal treatments were evaluated with voriconazole and fluconazole at 0.5, 1 and 5 mg/kg once a day. All treatment regimens were given on days 1-5 post-challenge. One day 6, the vaginas were swabbed to assess treatment effects.', 'Mice treated orally with voriconazole at >or=10 mg/kg and fluconazole at >or=20 mg/kg showed significantly reduced fungal counts over controls (P = 0.0002-0.007). Significant differences were found between the groups that received voriconazole at 20 mg/kg once or twice daily and those that received fluconazole at 20 mg/kg once or twice daily, orally (P = 0.010 and 0.001, respectively). Mice treated with voriconazole or fluconazole administered intravaginally at >or=0.5 mg/kg exhibited a reduced fungal burden when compared with the control group (P = 0.0002-0.007). There was no statistically significant difference in fungal burden between topical treatment with doses of 0.5, 1 and 5 mg/kg once daily of voriconazole or fluconazole. Sterilization of vaginas was not observed with voriconazole and fluconazole without taking into consideration the therapeutic modality.",
            "output": [
                "Do therapeutic efficacy of voriconazole against a fluconazole-resistant Candida albicans isolate in a vaginal model?"
            ]
        },
        {
            "id": "task847-b4d7c9a1540d4103b691403d152961b7",
            "input": "Advanced glycation end products (AGEs) have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To investigate the role of AGE formation in pulmonary fibrosis, we used a bleomycin (BLM)-stimulated rat model treated with aminoguanidine (AG), a crosslink inhibitor of AGE formation.', 'Rats were intratracheally instilled with BLM (5 mg/kg) and orally administered with AG (40, 80, 120 mg/kg) once daily for two weeks. AGEs level in lung tissue was determined by ELISA and pulmonary fibrosis was evaluated by Ashcroft score and hydroxyproline assay. The expression of heat shock protein 47 (HSP47), a collagen specific molecular chaperone, was measured with RT-PCR and Western blot. Moreover, TGFbeta1 and its downstream Smad proteins were analyzed by Western blot.', 'AGEs level in rat lungs, as well as lung hydroxyproline content and Ashcroft score, was significantly enhanced by BLM stimulation, which was abrogated by AG treatment. BLM significantly increased the expression of HSP47 mRNA and protein in lung tissues, and AG treatment markedly decreased BLM-induced HSP47 expression in a dose-dependent manner (p < 0.05). In addition, AG dose-dependently downregulated BLM-stimulated overexpressions of TGFbeta1, phosphorylated (p)-Smad2 and p-Smad3 protein in lung tissues.",
            "output": [
                "Does blockade of advanced glycation end product formation attenuate bleomycin-induced pulmonary fibrosis in rats?"
            ]
        },
        {
            "id": "task847-5bdab1a0968d4cee90cfe7f12c8840bf",
            "input": "Water stress during grain filling has a marked effect on grain yield, leading to a reduced endosperm cell number and thus sink capacity to accumulate dry matter. The bread wheat cultivar Chinese Spring (CS), a Chinese Spring terminal deletion line (CS_5AL-10) and the durum wheat cultivar Creso were subjected to transcriptional profiling after exposure to mild and severe drought stress at the grain filling stage to find evidences of differential stress responses associated to different wheat genome regions.', 'The transcriptome analysis of Creso, CS and its deletion line revealed 8,552 non redundant probe sets with different expression levels, mainly due to the comparisons between the two species. The drought treatments modified the expression of 3,056 probe sets. Besides a set of genes showing a similar drought response in Creso and CS, cluster analysis revealed several drought response features that can be associated to the different genomic structure of Creso, CS and CS_5AL-10. Some drought-related genes were expressed at lower level (or not expressed) in Creso (which lacks the D genome) or in the CS_5AL-10 deletion line compared to CS. The chromosome location of a set of these genes was confirmed by PCR-based mapping on the D genome (or the 5AL-10 region). Many clusters were characterized by different level of expression in Creso, CS and CS_AL-10, suggesting that the different genome organization of the three genotypes may affect plant adaptation to stress. Clusters with similar expression trend were grouped and functional classified to mine the biological mean of their activation or repression. Genes involved in ABA, proline, glycine-betaine and sorbitol pathways were found up-regulated by drought stress. Furthermore, the enhanced expression of a set of transposons and retrotransposons was detected in CS_5AL-10.",
            "output": [
                "Does transcriptional profiling in response to terminal drought stress reveal differential responses along the wheat genome?"
            ]
        },
        {
            "id": "task847-5265df8b038147aaa248a98f76300d99",
            "input": "Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel), because of large variances in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'typical' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique.\", \"The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N = 38) falling outside of the control group (N = 39) 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subgroups was observed between subjects with lower cerebellar declive (LCD) grey matter volumes than controls and subjects with higher cerebellar declive (HCD) grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic subjects, so that lower and higher lentiform grey matter volumes compared to controls differently modulated the phonological and lexical performances. Best performances (observed in controls) corresponded to an optimal value of grey matter and they dropped for higher or lower volumes.",
            "output": [
                "Does brain classification reveal the right cerebellum as the best biomarker of dyslexia?"
            ]
        },
        {
            "id": "task847-7a0f35bbe5e84d4fb391c47e3a0dbd01",
            "input": "Regulatory T cells (Tregs) are essential in the control of tolerance. Evidence implicates Tregs in human autoimmune conditions. Here we investigated their role in systemic sclerosis (SSc).', 'Patients were subdivided as having limited cutaneous SSc (lcSSc, n = 20) or diffuse cutaneous SSc (dcSSc, n = 48). Further subdivision was made between early dcSSc (n = 24) and late dcSSc (n = 24) based upon the duration of disease. 26 controls were studied for comparison. CD3+ cells were isolated using FACS and subsequently studied for the expression of CD4, CD8, CD25, FoxP3, CD127, CD62L, GITR, CD69 using flow cytometry. T cell suppression assays were performed using sorted CD4CD25(high)CD127(-) and CD4CD25(low)CD127(high) and CD3(+) cells. Suppressive function was correlated with CD69 surface expression and TGFbeta secretion/expression. The frequency of CD4(+)CD25(+) and CD25(high)FoxP3(high)CD127(neg) T cells was highly increased in all SSc subgroups. Although the expression of CD25 and GITR was comparable between groups, expression of CD62L and CD69 was dramatically lower in SSc patients, which correlated with a diminished suppressive function. Co-incubation of Tregs from healthy donors with plasma from SSc patients fully abrogated suppressive activity. Activation of Tregs from healthy donors or SSc patients with PHA significantly up regulated CD69 expression that could be inhibited by SSc plasma.",
            "output": [
                "Is increased frequency and compromised function of T regulatory cells in systemic sclerosis ( SSc ) related to a diminished CD69 and TGFbeta expression?"
            ]
        },
        {
            "id": "task847-0ce943f494ef428b968d18d9967a9d61",
            "input": "Given the variable response to cognitive-behavioral therapy (CBT) when added to antipsychotic medication in psychosis and the evidence for a role of pretherapy level of frontal lobe-based cognitive function in responsiveness to CBT in other disorders, this study examined whether pretherapy brain activity associated with working memory neural network predicts clinical responsiveness to CBT in schizophrenia.', 'Fifty-two outpatients stable on medication with at least one distressing symptom of schizophrenia and willing to receive CBT in addition to their usual treatment and 20 healthy participants underwent functional magnetic resonance imaging during a parametric n-back task. Subsequently, 26 patients received CBT for psychosis (CBT+treatment-as-usual [TAU], 19 completers) for 6-8 months, and 26 continued with TAU alone (17 completers). Symptoms in both patient groups were assessed (blindly) at entry and follow-up.', 'The CBT+TAU and TAU-alone groups did not differ clinically or in performance at baseline. The CBT+TAU group showed significant improvement in relation to the TAU-alone group, which showed no change, at follow-up. Stronger dorsolateral prefrontal cortex (DLPFC) activity (within the normal range) and DLPFC-cerebellum connectivity during the highest memory load condition (2-back > 0-back) were associated with post-CBT clinical improvement.",
            "output": [
                "Does dorsolateral prefrontal cortex activity predict responsiveness to cognitive-behavioral therapy in schizophrenia?"
            ]
        },
        {
            "id": "task847-aaedcf775cf34bf7800646f6740ebea9",
            "input": "Childhood sexual abuse (CSA) has been associated with alterations in brain morphology using region of interest analyses that have focused on stress-sensitive target regions. This study was designed to ascertain the effects on gray matter volume (GMV) of exposure to CSA in healthy young adult college students selected based on exposure history regardless of psychiatric outcome. Voxel-based morphometry (VBM) provided unbiased delineation of the most significantly affected brain regions.', 'High-resolution T1-weighted magnetic resonance imaging (MRI) datasets were obtained for 23 unmedicated female subjects with CSA and 14 healthy female control subjects of equivalent age and socioeconomic status with no history of trauma. Cortical surface-based analysis (FreeSurfer) was performed to verify VBM results.', 'Gray matter volume was reduced by 12.6% and 18.1% in right and left primary visual (V1) and visual association cortices of abused subjects. This reduction was directly related to duration of CSA before age 12. Gray matter volume of left and right V1 correlated with measure of visual memory (r = .353, p = .032 and r = .448, p = .005). Cortical surface-based analysis indicated that GMV of abused subjects was reduced in the left fusiform (p = .004), left middle occipital (p = .04), and right lingual (p = .002) gyri.",
            "output": [
                "Is childhood sexual abuse associated with reduced gray matter volume in visual cortex of young women?"
            ]
        },
        {
            "id": "task847-d65c8830a45745e7b8edd12230a5d8c3",
            "input": "Alcohol dependence is often associated with impulsivity, which may be correlated with dysfunction of the brain reward system. We explored whether functional brain activation during anticipation of incentive stimuli is associated with impulsiveness in detoxified alcoholics and healthy control subjects.', 'Nineteen detoxified male alcoholics and 19 age-matched healthy men participated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay (MID) task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain, avoidance of monetary loss, or no consequence. Impulsivity was assessed with the Barratt Impulsiveness Scale-Version 10 (BIS-10).', 'Detoxified alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy control subjects. Low activation of the ventral striatum and anterior cingulate during gain anticipation was correlated with high impulsivity only in alcoholics, not in control subjects.",
            "output": [
                "Does ventral striatal activation during reward anticipation correlate with impulsivity in alcoholics?"
            ]
        },
        {
            "id": "task847-22ac8174809943b1b90f95ca5d5207c1",
            "input": "During the first trimester of pregnancy, HIV-1 mother-to-child transmission is relatively rare despite the permissivity of placental cells to cell-to-cell HIV-1 infection. The placenta interacts directly with maternal uterine cells (decidual cells) but the physiological role of the decidua in the control of HIV-1 transmission and whether decidua could be a source of infected cells is unknown.', 'To answer to this question, decidual mononuclear cells were exposed to HIV-1 in vitro. Decidual cells were shown to be more susceptible to infection by an R5 HIV-1, as compared to an X4 HIV-1. Infected cells were identified by flow cytometry analysis. The results showed that CD14(+) cells were the main targets of HIV-1 infection in the decidua. These infected CD14(+) cells expressed DC-SIGN, CD11b, CD11c, the Fc gamma receptor CD16, CD32 and CD64, classical MHC class-I and class-II and maturation and activation molecules CD83, CD80 and CD86. The permissivity of decidual tissue was also evaluated by histoculture. Decidual tissue was not infected by X4 HIV-1 but was permissive to R5 HIV-1. Different profiles of infection were observed depending on tissue localization.",
            "output": [
                "Do antigen-presenting cells represent targets for R5 HIV-1 infection in the first trimester pregnancy uterine mucosa?"
            ]
        },
        {
            "id": "task847-7df0737c1e474000845cce636f3af41a",
            "input": "The Duffy blood group (Fy) antigen functions as the receptor whereby the malarial parasite Plasmodium vivax invades reticulocytes. In this study, we evaluated an autologous blood donation model to measure Fy expression during the anticipated response to blood loss.', 'This study aims to examine Fy expression following anticipated reticulocytosis in response to blood loss from autologous whole blood donation.', 'Subjects were healthy blood donors presenting for planned collection of two or three autologous units. Whole blood (450 ml +/- 10%) was collected and processed. Blood samples for Fy testing were obtained from the donations. These were assayed by flow cytometry by measuring binding of a phycoerythrin-labelled anti-Fy6 antibody and compared against reticulocyte numbers. Reticulocyte numbers were measured using thiazole orange. Results were compared from baseline (first donation) with samples at second and, if available, third, donations. Phenotyping for Fy a and b antigens was performed.', 'Reticulocytes increased by a mean of 37% over baseline [0.93% (range 0.31-1.93) to 1.23% (0.32-3.51%)] following donation of two (n = 32) or three (n = 9) autologous whole blood units. Absolute reticulocyte count remained low. Mean and median Fy expression on mature red blood cells and reticulocytes did not change from baseline levels despite individual variation. No apparent relationship to serologically determined Fy a and/or b antigen status was present.",
            "output": [
                "Does duffy antigen expression on reticulocytes alter following blood loss in an autologous donation model?"
            ]
        },
        {
            "id": "task847-61725f252e2b45f7b11a64ff3130dbe6",
            "input": "Accumulated evidence suggests that oxidative stress is involved in amyloid beta (Abeta)-induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silibinin improves Abeta-induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by Abeta(25-35) in mice.', 'Aggregated Abeta(25-35) (3 nmol) was intracerebroventricularly administered to mice. Treatment with silibinin (2, 20 and 200 mg.kg(-1), once a day, p.o.) was started immediately after the injection of Abeta(25-35). Locomotor activity was evaluated 6 days after the Abeta(25-35) treatment, and cognitive function was evaluated in a Y-maze and novel object recognition tests 6-11 days after the Abeta(25-35) treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the Abeta(25-35) injection.', 'Silibinin prevented the memory impairment induced by Abeta(25-35) in the Y-maze and novel object recognition tests. Repeated treatment with silibinin attenuated the Abeta(25-35)-induced accumulation of malondialdehyde and depletion of glutathione in the hippocampus.",
            "output": [
                "Does silibinin prevent amyloid beta peptide-induced memory impairment and oxidative stress in mice?"
            ]
        },
        {
            "id": "task847-041f3026252646abbe4b64d4e1badaa4",
            "input": "Recent data suggest that sub-clinical structural abnormalities may be part of the Brugada syndrome (BrS) phenotype, a disease traditionally thought to occur in the structurally normal heart. In this study, we carried out detailed assessment of cardiac morphology and function using cardiac magnetic resonance imaging (CMRI).', 'Thirty consecutive patients with BrS were compared with 30 sex- (26/4 male/female), body surface area- (+/-0.2 m(2)), and age-matched (+/-5 years) normal volunteers. CMRI exam included long- and short-axis ECG-gated breath-hold morphological T1-TSE sequences for fatty infiltration and cine-SSFP sequences for kinetic assessment. Fatty infiltration was not found in any subject. Patients with BrS compared with normal subjects showed higher incidence of mild right ventricle (RV) wall-motion abnormalities [15 (50%) vs. 5 (17%) subjects (P = 0.006) with reduced radial fractional shortening in more than two segments], reduction of outflow tract ejection fraction (49 +/- 11% vs. 55 +/- 10%; P = 0.032), enlargement of the inflow tract diameter (46 +/- 4 vs. 41 +/- 5 mm, P < 0.001 in short-axis; 46 +/- 4 vs. 42 +/- 5 mm, P = 0.001 in four-chamber long-axis view) and area (22 +/- 2 vs. 20 +/- 3 cm(2); P = 0.050), and of global RV end-systolic volume (34 +/- 10 vs. 30 +/- 6 mL/m(2); P = 0.031) but comparable outflow tract dimensions, global RV end-diastolic volume, left ventricle parameters, and atria areas.",
            "output": [
                "Do magnetic resonance investigations in Brugada syndrome reveal unexpectedly high rate of structural abnormalities?"
            ]
        },
        {
            "id": "task847-48a3f86c547f4dc1b5e5a12973a32fb8",
            "input": "Circulating tissue factor (TF) has been linked to thrombus propagation. Our group demonstrated that platelets possess mechanisms to capture TF-rich microvesicles (TF-MVs). Serotonin facilitates the development of platelets with increased procoagulant activity. An enhanced platelet serotonin uptake has been identified with increased cardiovascular risk. We have investigated the involvement of serotonergic mechanisms facilitating the interaction of human platelets with TF-MVs. Inhibitory strategies aimed at blocking serotonin and coagulation mechanisms were also studied.', 'Standard aggregometry, flow cytometry, electron microscopy, and thrombin generation assays were performed. TF-MVs induced platelet aggregation in heparinized platelet-rich plasma (PRP) samples; this aggregation was further accelerated by serotonin. In washed platelets, serotonin enhanced platelet aggregation to TF-MVs with a maximum peak of 55.9 +/- 1.8 vs. 48.7 +/- 2.1% (P < 0.05). Inhibitory strategies with a selective serotonin re-uptake inhibitor and with lepirudin decreased these aggregations. Ultrastructural analysis revealed that serotonin induced platelet pseudopodia formation, thus facilitating the engulfment of TF-MVs. In general, serotonin significantly enhanced (P < 0.05) thrombin generation and the expression of activation markers and procoagulant activity in platelets measured for TF-MVs alone.",
            "output": [
                "Does serotonin enhance platelet procoagulant properties and their activation induced during platelet tissue factor uptake?"
            ]
        },
        {
            "id": "task847-40d9d1e089624532b4d1119af3c47385",
            "input": "Cytoglobin (Cygb) was first described in 2002 as an intracellular globin of unknown function. We have previously shown the downregulation of cytoglobin as a key event in a familial cancer syndrome of the upper aerodigestive tract.', 'Cytoglobin expression and promoter methylation were investigated in sporadic head and neck squamous cell carcinoma (HNSCC) using a cross-section of clinical samples. Additionally, the putative mechanisms of Cygb expression in cancer were explored by subjecting HNSCC cell lines to hypoxic culture conditions and 5-aza-2-deoxycitidine treatment.', 'In clinically derived HNSCC samples, CYGB mRNA expression showed a striking correlation with tumour hypoxia (measured by HIF1A mRNA expression P=0.013) and consistent associations with histopathological measures of tumour aggression. CYGB expression also showed a marked negative correlation with promoter methylation (P=0.018). In the HNSCC cell lines cultured under hypoxic conditions, a trend of increasing expression of both CYGB and HIF1A with progressive hypoxia was observed. Treatment with 5-aza-2-deoxycitidine dramatically increased CYGB expression in those cell lines with greater baseline promoter methylation.",
            "output": [
                "Is cytoglobin upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer?"
            ]
        },
        {
            "id": "task847-e40d068003cd4e78a6298c74cbc762b2",
            "input": "To ascertain the predictive role of longitudinally acquired biochemical measures of cartilage turnover in relation to X-ray defined knee osteoarthritis (OAK), knee pain and functioning.', \"This is a feasibility study based on 72 enrollees of the Michigan site of Study of Women's Health Across the Nation (SWAN), a longitudinal, population-based cohort study with 11 annual visits to characterize health at the mid-life. At visits in 1996, 1998 and 2007, radiographs were evaluated for the presence of OAK [>or=2 on the Kellgren and Lawrence (K-L) scale]. Knee pain and stiffness were assessed by interview. Functioning was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Cartilage oligomeric matrix protein (COMP) and Type II collagen telopeptides (CTX-II) were assayed in serum and urine samples collected on alternate years from 1997 to 2006. We related trajectories of the cartilage biochemical markers from these five time points to OAK severity (no OAK, K-L score<2; mild OAK, K-L score=2; moderate/severe OAK, K-L score=3 or 4), pain, stiffness, or functioning, using longitudinal non-linear mixed modeling.\", 'The 2007 prevalence of X-ray defined OAK was 50% in these 72 women. Upward trajectories of COMP (P=0.02) and CTX-II (P=0.006) were associated with increased OAK severity and body size. COMP trajectories were associated with pain and stiffness, but not functioning. CTX-II trajectories were associated with stiffness scores, but not knee pain or functioning scores.",
            "output": [
                "Do longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women?"
            ]
        },
        {
            "id": "task847-3a89ee8f5a9d4d348400c6125ef3173d",
            "input": "To test whether oral L-81 treatment could improve the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver.', 'Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mechanism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.', 'Treatment of db/db mice with L-81 significantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also significantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter.",
            "output": [
                "Does pluronic L-81 ameliorate diabetic symptoms in db/db mice through transcriptional regulation of microsomal triglyceride transfer protein?"
            ]
        },
        {
            "id": "task847-68a44afa70f343f69df85c906df792dd",
            "input": "Preoperative chemoradiotherapy is one of the key strategies for the improvement of survival in pancreatic cancer; however, no method to predict the response has yet been established. The aim of this study was to prospectively evaluate the predictive value of REG4, a new member of the regenerating (REG) islet-derived family of proteins.', 'Stably REG4-expressing cells were established from a pancreatic cancer cell line and exposed in vitro to gamma-ray or gemcitabine to investigate the relevance of REG4 to the resistance to chemotherapy or radiotherapy. In 23 patients with resectable pancreatic cancer, the serum concentration of REG4 was measured before preoperative chemoradiotherapy, and the histologic response was evaluated after the surgery.', 'A 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and fluorescence activated cell scanning (FACS) revealed that REG4-overexpressing cells were resistant to gamma-radiation but showed a modest resistance to gemcitabine. The patients with a higher REG4 level, but not carcinoembryonic antigen or CA-19-9, showed an unfavorable histologic response to chemoradiotherapy (Spearman, rho = 0.439, P = 0.039). The patients showing a higher REG4 level experienced local recurrence postoperatively.",
            "output": [
                "Is serum REG4 level a predictive biomarker for the response to preoperative chemoradiotherapy in patients with pancreatic cancer?"
            ]
        },
        {
            "id": "task847-756db0a57eb94b7b8d972b2ebcb63bfb",
            "input": "A malaria management protocol was developed and implemented at a tertiary care children's hospital in September 1999. We retrospectively evaluated children admitted with malaria 10-years preimplementation and 7-years postimplementation to determine the impact the protocol had on management and time delay to appropriate antimalarial therapy.\", 'This before and after study compared all admissions with the discharge diagnosis of malaria in the study period. Retrospective chart review was used to determine the time from emergency department (ED) registration to administration of antimalarial treatment. Other outcomes measured included mortality, length of hospital stay, and intensive care unit admission.', 'Fifty-eight admissions were identified during the defined period, most of which were due to Plasmodium falciparum[r] malaria. Thirty-one (53.4%) cases were before implementation of the protocol. Children were more likely to receive appropriate investigations to assess for possible severe malaria before transfer from the ED to the ward after protocol implementation (18% vs. 63%, P = 0.005). Analysis of index cases of malaria, excluding patients diagnosed after the diagnosis of a sibling, showed there was a significant reduction in time to medication administration (8 vs. 5.5 hours, P = 0.036).",
            "output": [
                "Does protocol for management of imported pediatric malaria decrease time to medication administration?"
            ]
        },
        {
            "id": "task847-dce50ed7a6224d75a80ba65857db3c31",
            "input": "To identify differences in perspectives that may complicate the process of joint decision making at the end of life, this study determined the agreement of family and staff perspectives about end-of-life experiences in nursing homes and residential care/assisted living communities and whether family and staff roles, involvement in care, and interaction are associated with such agreement.', 'This cross-sectional study examined agreement in 336 family-staff pairs of postdeath telephone interviews conducted as part of the Collaborative Studies of Long-Term Care. Eligible deaths occurred in or within 3 days of leaving one of a stratified random sample of 113 long-term care facilities in four states and after the resident had lived in the facility (3)15 days of the last month of life. McNemar p values and kappas were determined for each concordance variable, and mixed logistic models were run.', \"Chance-adjusted family-staff agreement was poor for expectation of death within weeks (66.9% agreement, kappa = .33), course of illness (62.9%, 0.18), symptom burden (59.6%, 0.18), and familiarity with resident's physician (59.2%, 0.05). Staff were more likely than family to expect death (70.2% vs 51.5%, p < .001) and less likely to report low symptom burden (39.6% vs 46.6%, p = .07). Staff involvement in care related to concordance and perspectives of adult children were more similar to those of staff than were other types of family members.",
            "output": [
                "Does concordance of family and staff member report about end of life in assisted living and nursing homes?"
            ]
        },
        {
            "id": "task847-8f77e432142e4f6bacd86649fd053b30",
            "input": "To examine whether neonatal seizures are associated with neurodevelopmental outcomes in infants with hypoxia-ischemia independent of the presence and severity of brain injury seen on magnetic resonance imaging (MRI).', 'We used multivariate regression to examine the independent effect of clinical neonatal seizures and their treatment on neurodevelopment in 77 term newborns at risk for hypoxic-ischemic brain injury. Clinical seizures were recorded prospectively, and high-resolution newborn MRI measured the severity of brain injury. The outcome measure was the Full-Scale Intelligence Quotient (FSIQ) of the Wechsler Preschool and Primary Scale of Intelligence-Revised and neuromotor score at age 4 years.', 'After controlling for severity of injury on MRI, the children with neonatal seizures had worse motor and cognitive outcomes compared with those without seizures. The magnitude of effect varied with seizure severity; children with severe seizures had a lower FSIQ than those with mild/moderate seizures (P < .0001).",
            "output": [
                "Are clinical Neonatal Seizures Independently Associated with Outcome in Infants at Risk for Hypoxic-Ischemic Brain Injury?"
            ]
        },
        {
            "id": "task847-1b6f35b31ad44e4ea687655d1e93e645",
            "input": "Angiopoietin-like protein 3, a liver-derived plasma protein, increases plasma triglycerides (TG) in mice by suppressing the activity of lipoprotein lipase, a key enzyme in plasma TG clearance. Uremic dyslipidemia is characterized by increased TG-rich lipoproteins such as very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), lowered high-density lipoprotein (HDL), and TG-enrichment of low-density lipoprotein (LDL) and HDL. Since the role of angiopoietin-like protein 3 (ANGPTL3) in uremic dyslipidemia is unknown, we examined its possible association with the lipoprotein abnormalities in patients with chronic renal failure (CRF).', 'The subjects were 202 hemodialysis patients, 44 predialysis patients with CRF and 148 healthy control subjects comparable in age and sex. Fasting plasma ANGPTL3 was measured by enzyme-linked immunoassay, and lipoproteins were fractioned by ultracentrifugation.', 'Median (25th-75th percentile range) ANGPTL3 levels were 523 (409-645) and 393 (308-511)ng/mL in hemodialysis and predialysis patients, respectively, which were significantly lower than the control level of 700 (570-875)ng/mL. In the total subjects, ANGPTL3 was inversely correlated with VLDL- and IDL-cholesterol levels, and positively with HDL-cholesterol. ANGPTL3 correlated inversely with TG/cholesterol ratios of both LDL and HDL. In multiple regression models, these associations, excluding TG/cholesterol ratio of LDL, remained significant and independent of possible confounders including age, sex, body mass index, insulin resistance index (HOMA-IR), and adiponectin, whereas the associations of ANGPTL3 with the lipoprotein parameters were less significant when apoC-II/C-III ratio was included in the models.",
            "output": [
                "Is plasma angiopoietin-like protein 3 ( ANGPTL3 ) concentration associated with uremic dyslipidemia?"
            ]
        },
        {
            "id": "task847-12ad565b8f2c475f83c16228679342b7",
            "input": "To determine whether the number and location of positive surgical margins (PSMs) in radical prostatectomy (RP) surgical specimens affect biochemical recurrence (BCR) rates.', 'The locations of PSMs were recorded for 1308 consecutive men who underwent RP between October 2000 and December 2006. BCR was defined as three consecutive prostate-specific antigen (PSA) level rises with the peak level >or=0.15 ng/mL. Multivariate regression analyses were used to identify preoperative predictors of PSMs and BCR. The estimated 5-year risk of BCR was calculated using the Kaplan-Meier method.', 'In all, 128 (9.8%) men had one or more PSMs. The mean body mass index, mean preoperative serum PSA level, the distributions of clinical stage and biopsy Gleason scores, and the presence or absence of biopsy perineural invasion were significantly different between men with or with no PSMs. In multivariate analysis, baseline serum PSA level, Gleason score and perineural invasion were independent preoperative predictors of PSMs. The 5-year actuarial BCR rates were dependent on the site of the PSM (P = 0.035) and not the number of PSMs (P = 0.18). The rank order of estimated 5-year BCR rates according to the site of PSMs were base > anterior > posterolateral > apex approximately posterior.",
            "output": [
                "Does site of positive surgical margins influence biochemical recurrence after radical prostatectomy?"
            ]
        },
        {
            "id": "task847-5bc0fb5a297249048b1853847fe25dfa",
            "input": "To assess, in a retrospective cohort, urinary tract urothelial carcinoma (UT-UC) in patients with various stages of chronic kidney disease (CKD) and their clinicopathological features, as patients with end-stage renal disease (ESRD) have a higher incidence of UT-UC, but the relationship between early stages of CKD and characteristics of UT-UC are less well known.', 'The study included 267 patients with pathologically confirmed UT-UC from January 1994 to December 2006; all had a physical examination (blood pressure), and measurements of laboratory data (serum creatinine, serum haemoglobin) and pathological data. The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Patients were divided into three groups by individual GFR (mL/min), i.e. >60 (no/mild CKD), 30-60 (CKD stage 3) and <30 (CKD stage 4/5).', 'The CKD stages included 81 (30.3%) patients with none/mild CKD, 121 (45.3%) with CKD stage 3 and 65 (24.3%) with CKD stage 4/5. There was a significant and parallel increase in the frequency of UT-UC as CKD severity increased from none/mild CKD to stage 3 (11% vs 55%), and from CKD stage 3 to 4/5 (55% vs 71%; P < 0.05). Pathologically, the frequency of high-grade and high T stage UT-UC in patients with CKD stage 3 (90% and 35%, respectively) and CKD stage 4/5 (91% and 29%, respectively) were significantly greater than in the group with none/mild CKD (P < 0.001). Advanced age and more distant metastasis were independent risk factors for patient survival.",
            "output": [
                "Does the aggressiveness of urinary tract urothelial carcinoma increase with the severity of chronic kidney disease?"
            ]
        },
        {
            "id": "task847-ee819697218741d484b857eb2828383d",
            "input": "The aim of this study was to analyze prosthetic maintenance in partially edentulous patients with removable prostheses supported by teeth and strategic implants.', 'Sixty patients with removable partial prostheses and combined tooth-implant support were identified within the time period from 1998 to 2006. One group consisted of 42 patients (planned group) with a reduced residual dentition and in need of removable partial dentures (RPDs) or overdentures in the maxilla and/or mandible. They were admitted consecutively for treatment. Due to missing teeth in strategic important positions, one or two implants were placed to improve symmetrical denture support and retention. The majority of residual teeth exhibited an impaired structural integrity and therefore were provided with root copings for denture retention. A few vital teeth were used for telescopic crowns. The anchorage system for the strategic implants was selected accordingly. A second group of 18 patients (repair group) wearing RPDs with the loss of one abutment tooth due to biologic or mechanical failure was identified. These abutment teeth were replaced by 21 implants, and patients continued to wear their original prostheses. The observation time for planned and repair groups was 12 months to 8 years. All patients followed a regular maintenance schedule. Technical or biologic complications with supporting teeth or implants and prosthetic service were registered regularly.', 'Three maxillary implants were lost after loading and three roots with copings had to be removed. Biologic problems included caries and periodontal/peri-implant infection with a significantly higher incidence in the repair group (P < .05). Technical complications with the dentures were rather frequent in both groups, mostly related to the anchorage system (matrices) of root copings and implants. Maintenance and complications were observed more frequently in the first year after delivery of the denture than in the following 3 years (P < .05). No denture had to be remade.",
            "output": [
                "Do removable dentures with implant support in strategic positions followed for up to 8 years?"
            ]
        },
        {
            "id": "task847-ec3b33bb030a4eafbc04839dcda3c847",
            "input": "Vitamin D is associated with a number of inflammatory diseases and plays a significant role in regulating bone metabolism. Serum calcifediol was demonstrated to be potentially associated with periodontal disease. The purpose of this study was to evaluate whether an association exists between plasma calcifediol concentrations and aggressive periodontitis (AgP) and whether plasma levels of bone-related biomarkers (osteocalcin, alkaline phosphatase, calcium, and phosphorus) regulated by vitamin D are related to AgP.', 'Sixty-six patients with generalized AgP, 52 patients with chronic periodontitis, and 60 healthy controls were included in this study. Periodontal examination consisted of probing depth, attachment loss, and bleeding index measurements. Hematic calcifediol and bone-related biomarker levels were detected using radioimmunity assay kits or a biochemical analyzer.', 'Plasma calcifediol levels in patients with AgP were higher than those of healthy controls (29.28 versus 21.60 nmol/l; P <0.05) and were statistically significantly correlated with bleeding index (r = 0.321; P <0.05). Plasma osteocalcin concentrations in patients with AgP were higher than those of healthy controls (0.90 versus 0.70 ng/ml; P <0.05). Serum inorganic phosphorus values of both periodontitis groups were lower than those of healthy controls (1.06 +/- 0.18 mmol/l and 1.10 +/- 0.15 mmol/l versus 1.26 +/- 0.17 mmol/l; P <0.05).",
            "output": [
                "Is elevated plasma calcifediol associated with aggressive periodontitis?"
            ]
        },
        {
            "id": "task847-2de880d3d6404353ab628f7840c79d88",
            "input": "It is evident that diabetes and periodontal disease are closely interrelated. Accumulation of advanced glycation end products (AGEs), coupled with exaggerated host responses to bacterial infection, may account for the increased periodontal destruction observed in patients with uncontrolled diabetes. The present study investigated the effects of AGEs on the viability of human gingival fibroblasts (HGFs) and the expression of types I and III collagen in HGFs.', 'The cell viability of HGFs was examined by methylthiazolet-etrazolium assay, whereas the expression of types I and III collagen message and protein was detected by real-time quantitative reverse transcription-polymerase chain reaction and sandwich enzyme-linked immunosorbent assay, respectively.', 'AGEs significantly suppressed the cell viability of HGFs from 24 to 72 hours (P <0.01). A high concentration of glucose (25 mmol/l) in the culture media exaggerated the inhibition of the survival rate of HGFs (P <0.01). The expression of collagen types I and III messages and proteins was significantly downregulated at 72 hours by AGEs in a concentration-dependent manner (P <0.05). Moreover, the synthesis of intracellular types I and III collagen protein was markedly inhibited by AGEs (P <0.05).",
            "output": [
                "Do advanced glycation end products inhibit the expression of collagens type I and III by human gingival fibroblasts?"
            ]
        },
        {
            "id": "task847-93e968849bf649a39543162546d1661a",
            "input": "The aim of this study was to evaluate the value and accuracy of multiplanar reconstruction (MPR) of three-dimensional (3D) transthoracic echocardiographic data sets in assessing mitral valve pathology in patients with surgical mitral valve prolapse (MVP).', 'Sixty-four patients with surgical MVP and preoperative two-dimensional (2D) and 3D transthoracic echocardiography were analyzed. The descriptions obtained by 3D MPR and 2D were compared in the context of the surgical findings.', 'Two-dimensional echocardiography correctly identified the prolapsing leaflets in 32 of 64 patients and 3D MPR in 46 of 64 patients (P=.016). Among the 27 patients with complex pathology (ie, more than isolated middle scallop of the posterior leaflet prolapse), 3D MPR identified 20 correctly, as opposed to 6 with 2D imaging (P<.001).",
            "output": [
                "Does multiplanar reconstruction of three-dimensional transthoracic echocardiography improve the presurgical assessment of mitral prolapse?"
            ]
        },
        {
            "id": "task847-6eeed7c7bd924ea2bb3ca6066d277462",
            "input": "We aimed to investigate whether and how the total flavonoid extracts (TFE) from Inula britannica L. block neointimal hyperplasia induced by balloon injury in rats.', 'Rats were administered orally TFE doses of 12.5, 25 and 50 mg/kg/d by gastric gavage from 3 days before balloon injury to 14 days after the injury. The ratio of intima (I) to media (M) thickness (I/M) in carotid arteries was examined by morphological analyses. The MDA content and SOD activity in plasma were measured. The O(2)(-) production in vascular tissues was detected in situ. The expression of p47(phox) in carotid arteries was analyzed by Western blot analysis and immunohistochemistry.', 'The rats treated with TFE 50 mg/kg/d showed a reduction in neointimal hyperplasia, and the ratio of I/M of balloon injured-carotid arteries was significantly reduced by over 70% after TFE treatment, compared with the injured group. The inhibitory effect of TFE on neointimal hyperplasia was almost consistent with that of atorvastatin, a positive control. The plasma SOD activity was obviously increased by TFE treatment (P<0.01), while plasma MDA production was markedly decreased by TFE treatment (P<0.05). On day 14 after balloon injury, the carotid arteries showed an increase in O(2)(-) production that was most evident in the neointimal and medial layer of the vessel. Thus, TFE significantly inhibited injury-induced O(2)(-) production and p47(phox) expression in carotid arteries.",
            "output": [
                "Do flavonoids from Inula britannica L. inhibit injury-induced neointimal formation by suppressing oxidative-stress generation?"
            ]
        },
        {
            "id": "task847-368da988056a45b2ad63db73afd05d47",
            "input": "To test the hypothesis that hyporesponsiveness to ghrelin due to reduced growth hormone (GH) contributes to the aging-related hyperinflammatory state in sepsis.', 'Sepsis and septic shock are a serious problem, particularly in the geriatric population. Ghrelin is an endogenous ligand for the GH secretagogue receptor 1a (GHSR1a, ie, ghrelin receptor). The decline in GH with age is directly associated with many adverse changes that occur with aging. However, the role of GH, ghrelin, and GHSR1a in the age-associated vulnerability to sepsis remains unknown.', 'Male Fischer 344 rats (young: 3 months; aged: 24 months) were used. Plasma GH levels, ghrelin receptor expression, and neuronal activity in the parasympathostimulatory nuclei of the brain stem in normal young and aged animals were measured. Endotoxemia was induced by intravenous injection of lipopolysaccharide (LPS, 15 mg/kg BW).', 'While LPS-induced release of proinflammatory cytokines from macrophages isolated from aged rats decreased, LPS injection resulted in an in vivo hyperinflammatory state. GH levels were lower in aged rats, which was associated with lower expression of GHSR1a in the dorsal vagal complex and a decrease in parasympathostimulatory neuronal activity. GHSR1a antagonist elevated LPS-induced cytokine release in young rats. GH increased GHSR-1a expression in the dorsal vagal complex in aged rats. Coadministration of ghrelin and GH, but not ghrelin alone or GH alone, markedly reduced cytokine levels and organ injury after endotoxemia in aged rats, which was associated with significantly elevated parasympathostimulatory neuronal activity.",
            "output": [
                "Does ghrelin hyporesponsiveness contribute to age-related hyperinflammation in septic shock?"
            ]
        },
        {
            "id": "task847-d02bb4c91b5f49e1a53a80229ffeb1a9",
            "input": "Continuity of care has traditionally been regarded as a core quality of general practice, but the long-term doctor-patient relationship has been put under pressure. In many places practices are expanding, with larger teams and more registered patients, thereby threatening the possibility of patients staying with their own general practitioner (GP). GPs often take it for granted that interpersonal continuity is valuable. However, little is known about how patient satisfaction is related to interpersonal continuity. The purpose of this study is to explore the creation of patient satisfaction or dissatisfaction in the interpersonal relation with the GP, and in a comprehensive way to investigate how this is related to continuity of care.', \"Qualitative study based on 22 interviews with patients from two practices in Denmark. A total of 12 patients saw a regular doctor and 10 saw an unfamiliar doctor. The patients were selected after an observed consultation and sampled purposefully according to reason for encounter, age and sex. Interpretative phenomenological analysis (IPA) was used to study how patients perceive meeting either a regular or an unfamiliar GP. The analysis explored the patients' perception of their interpersonal relationship with their GP, and interpreted the accounts by using social psychological theories.\", \"A long-term continuous relationship with the GP could be satisfactory, but it could also be the reverse. The same pattern was shown in case of an unfamiliar GP. Therefore, patient satisfaction and interpersonal continuity were not causally related. On the contrary, there was a general pattern of how the satisfactory and trustful doctor-patient relationship from the patients' point of view could be created, maintained or destroyed. A pattern where the process of recognition, by respecting and remembering, on the one hand created and maintained satisfaction while humiliation on the other hand destroyed satisfaction in the relationship.",
            "output": [
                "Does it 's all about recognition ! Qualitative study of the value of interpersonal continuity in general practice?"
            ]
        },
        {
            "id": "task847-896979455fbc41e0a85571543cece40b",
            "input": "Alternative splicing is an important mechanism for generating functional and evolutionary diversity of proteins in eukaryotes. Here, we studied the frequency and functionality of recently gained, rodent-specific alternative exons.', 'We projected the data about alternative splicing of mouse genes to the rat, human, and dog genomes, and identified exons conserved in the rat genome, but missing in more distant genomes. We estimated the frequency of rodent-specific exons while controlling for possible residual conservation of spurious exons. The frequency of rodent-specific exons is higher among predominantly skipped exons and exons disrupting the reading frame. Separation of all genes by the rate of sequence evolution and by gene families has demonstrated that rodent-specific cassette exons are more frequent in rapidly evolving genes and in rodent-specific paralogs.",
            "output": [
                "Are rodent-specific alternative exons more frequent in rapidly evolving genes and in paralogs?"
            ]
        },
        {
            "id": "task847-7975f09d00c14070899c93f787038bd9",
            "input": "Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that plays a role in angiogenesis and microvascular permeability. This study was conducted to determine whether common sequence variation in the VEGFA gene plays a role in the development of diabetic retinopathy (DR).', 'Five hundred fifty-four subjects with diabetes mellitus (DM) including 190 type 1 DM (T1DM) and 364 type 2 DM (T2DM) were recruited. The study group consisted of 235 participants without DR, 158 with nonproliferative DR (NPDR), 132 with proliferative DR (PDR), and 93 with clinically significant macular edema (CSME). Blinding DR was defined as severe NPDR, PDR, or CSME. Fifteen VEGFA tag single-nucleotide polymorphisms (SNPs) were genotyped in all subjects and tested for association with blinding DR.', 'Multiple tag SNPs in the VEGFA gene were associated with blinding DR. After controlling for sex, HbA1c, and duration of disease, in T1DM, the AA genotype of rs699946 (P = 0.007, odds ratio [OR], 4.1; 95% confidence interval [CI], 1.5-11.4) and the GG genotype of rs833068 (P = 0.017, OR, 3.1; 95% CI, 1.3-7.2) were most significantly associated. In T2DM, the C allele of rs3025021 (P = 0.002; OR, 3.8; 95% CI, 1.5-10.0) and the G allele of rs10434 (P = 0.002; OR, 2.6; 95% CI, 1.3-5.3) were most significantly associated with blinding DR. Haplotype analyses suggested an important role for the haplotype TCCGCG in blinding DR (P = 0.0004).",
            "output": [
                "Does common sequence variation in the VEGFA gene predict risk of diabetic retinopathy?"
            ]
        },
        {
            "id": "task847-af4d077a318942549cccfc1a264fc962",
            "input": "Shift-work and a sedentary lifestyle are risk factors for raised blood pressure (BP). Exercise can reduce BP in diurnally-active individuals, but it is unknown whether postexercise hypotension persists when people are active and eating at night. We present the first investigation into the acute effects of exercise on BP monitored during simulated night-work.', 'Nine normotensive participants, aged 20-42 years, completed at least two crossover trials beginning at 1800 hours. Between 1900 and 2000 hours, participants either rested or exercised at 50% peak oxygen uptake (VO(2peak)) and then remained awake throughout the night, completing various tasks until 0515 hours. Six participants completed a total of four trials in which they exercised or rested, whereas either one standardized (60 kJ/kg) meal at 2200 hours or two smaller (30 kJ/kg) meals at 2200 and 0200 hours were eaten. Systolic and diastolic BP, mean arterial pressure (MAP), heart rate (HR), and wrist activity were recorded every 30 min.', 'Following exercise, MAP was significantly (P < 0.0005) lower throughout the night-shift compared with no prior exercise (95% confidence limits for reduction: 4-7 mm Hg). The postexercise reductions in systolic BP and MAP were not moderated by diet, but the reduction in diastolic BP was slightly greater when only one meal was eaten (P < 0.0005). BP was lower even though wrist activity and HR were significantly higher following exercise (P < 0.0005).",
            "output": [
                "Does prior exercise lower blood pressure during simulated night-work with different meal schedules?"
            ]
        },
        {
            "id": "task847-81ce050ca1ae454a809399394f4e1f73",
            "input": "Immunosuppression after burn injury increases the risk of sepsis and multiple organ failure. We examined changes of immune function in mice after burn injury and investigated the immunostimulatory effect of oligodeoxynucleotides containing CpG motifs.', 'Male BALB/c mice (8-10 wk old) received a full-thickness burn to 20% of their body surface area, after which the immunological parameters of splenic macrophages were evaluated. To assess the immunostimulatory effect of oligodeoxynucleotide treatment, splenic macrophages harvested from burned mice were incubated with oligodeoxynucleotides. Then cytokine production and major histocompatibility complex class II antigen expression were measured. To assess the in vivo effect of oligodeoxynucleotides, intraperitoneal administration was done on day 4 after burn injury, and class II antigen expression by splenic macrophages was measured 10 d later.', 'Class II antigen expression and the synthesis of cytokines (interleukin-12, tumor necrosis factor-alpha, interleukin-6, and interleukin-1) by splenic macrophages were significantly reduced after burn injury, while incubation of splenic macrophages from burned mice with oligodeoxynucleotides partially enhanced the production of interleukin-12, tumor necrosis factor-alpha, interleukin-6, and interleukin-1. In addition, intraperitoneal administration of oligodeoxynucleotides enhanced class II antigen expression by splenic macrophages.",
            "output": [
                "Do cpG oligonucleotides activate the immune response in burned mice?"
            ]
        },
        {
            "id": "task847-a14d49ed9e04430a83233d452c8feeaa",
            "input": "Respiratory failure is a major complication after cardiac surgery. The purpose was to evaluate the impact of minimally invasive aortic valve replacement (mini AVR) on the occurrence of left lower lobe atelectasis (LLLA) in the cardiac intensive care unit (ICU).', '98 patients were scheduled to undergo mini AVR. 14 of these patients were converted to a full sternotomy due to technical problems. These patients were compared to a group of 50 patients having planned AVR through a full sternotomy. The incidence of LLLA was evaluated on the first postoperative chest X-ray in the cardiac ICU.', 'In the group having completed mini AVR 20/84 (24%) had a partial LLLA while in the group having extension to a full sternotomy 9/14 (64%) had LLLA lobe (P<0.005). In the group of 50 patients who had AVR through a full sternotomy, 27 patients (54%) had LLLA in the ICU which is also significantly higher (P<0.008) than the percentage of atelectasis in the mini AVR group.",
            "output": [
                "Does minimally invasive aortic valve replacement reduce atelectasis in cardiac intensive care?"
            ]
        },
        {
            "id": "task847-1a5e9b5f7ffc4f299f969922d6b0e20a",
            "input": "Older adults often show sustained attention toward positive information and an improved memory for positive events. Little is known about the neural changes that may underlie these effects, although recent research has suggested that older adults may show differential recruitment of prefrontal regions during the successful encoding of emotional information. In the present study, effective connectivity analyses examined the network of regions that college-age and older adults recruited during the encoding of positive and negative images.', \"Participants viewed positive and negative images while undergoing a functional magnetic resonance imaging (fMRI) scan. Structural equation modeling was used to compare young and older adults' connectivity among regions of the emotional memory network while they encoded negative or positive items.\", 'Aging did not impact the connectivity among regions engaged during the encoding of negative information, but age differences did arise during the encoding of positive information. Most notably, in older adults, the ventromedial prefrontal cortex and amygdala strongly influenced hippocampal activity during the encoding of positive information. By contrast, in young adults, a strong thalamic influence on hippocampal activity was evident during encoding.",
            "output": [
                "Are there age-related changes in neural connectivity during the encoding of positive , but not negative , information?"
            ]
        },
        {
            "id": "task847-8a507adcbfab4d6f9975afdc7dc840dd",
            "input": "This study determined the effect of a structured isotonic strength training (ST) program on left ventricular (LV) function (ejection fraction, stroke volume, and end-diastolic and end-systolic volumes) and physical fitness (6-minute walk test, upper body strength, lower body strength, and body composition) in patients with New York Heart Association class II and III heart failure.', 'Sixteen patients were randomized into 2 groups, ST and usual care. The ST group (10 patients) performed 24 ST exercise sessions (3 per week, 8 weeks), while the usual care (6 patients) group followed routine medical care. The structured isotonic ST program involved 12 different exercises on circuit weight machines. LV function (3D echocardiography) and physical fitness were assessed at baseline and 8 weeks.', 'Modest improvements (P < .05) in resting ejection fraction (0.32-0.37) and stroke volume (46 to 53 mL/beat), as well as in muscular strength and 6-minute walk distance, were found after training.",
            "output": [
                "Does resistance exercise training improve heart function and physical fitness in stable patients with heart failure?"
            ]
        },
        {
            "id": "task847-42aa20526ed04fd7abfae3bb09201765",
            "input": "We investigated the difference in incidence of acute akathisia related to the rate of infusion in patients receiving metoclopramide for acute nausea, vomiting, or migraine headache in the emergency department (ED).', 'Randomized, prospective, double-blind clinical trial of patients aged 18 years and older who were to receive intravenous metoclopramide for the treatment of nausea, vomiting, or headache were eligible. Patients were excluded if they were taking medications that might mimic or mask akathisia, had a movement disorder, renal insufficiency, or were unable or unwilling to consent. Pregnant women and prisoners were also excluded. Subjects were randomized to receive 1 of 2 accepted metoclopramide administration regimens. The regimens included 10 mg of metoclopramide administered either as a 2-minute bolus (BG) or as a slow infusion for 15 minutes (IG). All patients received a normal saline placebo at the opposite rate to maintain blinding. The main outcome was development of akathisia noted at 60 minutes after drug administration as measured either with The Prince Henry Hospital akathisia rating scale or by sudden unexplained departure from the ED during treatment.', 'One hundred twenty-seven patients were eligible for the study. Fifty-nine patients met exclusion criteria. Of the remaining 68 patients, 36 were randomized to the BG and 32 were randomized to the IG. In the BG, 11.1% of patients developed akathisia compared with 0% in the IG (P = .026). Four patients developed akathisia based on the scale and 2 departed suddenly from the ED.",
            "output": [
                "Does slower infusion of metoclopramide decrease the rate of akathisia?"
            ]
        },
        {
            "id": "task847-784017fcd31444939289894a264a05ce",
            "input": "The purpose of the study is to investigate the influence of cardiopulmonary resuscitation (CPR) time before the first defibrillation.', 'The present study retrospectively analyzed the Utstein template records from April 1, 2002, to June 30, 2005. Patients who had out-of-hospital-witnessed cardiac arrest caused by cardiac disease and who presented with ventricular fibrillation (VF) as the initial cardiac rhythm were included in the study. Before April 1, 2003, the emergency medical technician (EMT) needed to obtain telephone permission before attempting defibrillation, and CPR was continued until permission was received (CPR first). On and after April 1, 2003, the EMT was immediately able to attempt a defibrillation without obtaining permission (shock first).', 'In 143 patients who had out-of-hospital-witnessed VF, 43 patients and 100 patients were treated with the CPR-first strategy and the shock-first strategy, respectively. The duration of CPR before the first defibrillation was longer in the CPR-first group than that in the shock-first group. The CPR-first group showed a higher rate of favorable neurologic outcome 30 days after (28% vs 14%; P = .048) and 1 year after cardiac arrest (26% vs 11%; P = .033) than those of the shock-first group. In the patients with witnessed VF, a stepwise multiple logistic regression analysis showed the CPR-first strategy to improve the neurologic outcome.",
            "output": [
                "Does shortening of cardiopulmonary resuscitation time before the defibrillation worsen the outcome in out-of-hospital VF patients?"
            ]
        },
        {
            "id": "task847-fee69aba2d5348a28bc69d5f1e8ece96",
            "input": "Total exercise duration and abnormal QRS score values are treadmill exercise testing (TET) prognostic parameters that have been shown to be significantly and independently associated with cardiac mortality. We evaluated the prognostic value of a new index (M score, Michaelides score) incorporating TET duration and QRS score values in a simple index.', 'In this study, we included 626 patients, who underwent TET and coronary arteriography. Cardiac catheterization showed the presence of coronary artery disease in 64.3% of these patients. The M score was calculated by adding the value of the Athens QRS score to the duration of TET (in minutes). The outcome measure was a composite of myocardial infarction or death. Patients were prospectively followed for 38+/-21 months (median 36 months).', \"The composite endpoint was more frequent among the patients of the 1st quartile (M-score values <-5.8). In univariate analysis, mortality of the first-quartile patients was significantly higher (14 vs. 1.1%, P<0.001). In multivariate Cox's regression analysis for age, sex, diabetes, smoking status, hypertension, hypercholesterolemia, maximum ST depression at TET, angina during TET, coronary artery disease on angiography, and echocardiographic left ventricular ejection fraction, the first quartile of M-score values was found to be independently associated with the composite endpoint (relative risk = 3.26, 95% confidence interval = 2.01-5.29, P<0.001).",
            "output": [
                "Does duration of treadmill exercise testing combined with QRS score predict adverse cardiac outcome at long-term follow-up?"
            ]
        },
        {
            "id": "task847-fc5da3dffa774e6f9727c369412d6d28",
            "input": "The objective of this study was to determine whether 16 weeks of resistance training (RT) can reduce the blood pressure response and improve the cardiovascular function of men aged 70-80 years during submaximum aerobic exercise.', 'Twenty-four men aged between 70 and 80 years were randomly assigned to an RT group (n = 12) and control group (n = 12). Training consisted of three sets of six to 10 repetitions at 70-90% of one repetition maximum, three times per week, on an incline squat machine for 16 weeks. Blood pressure and cardiovascular function were assessed during submaximum cycle exercise at 40 W, and 50 and 70% of maximum oxygen consumption (VO2max) before training and after 16 weeks of training. Leg strength and VO2max were assessed every 4 weeks of the 16-week study.', 'At 40 W, heart rate, systolic blood pressure, and rate pressure product were lower and stroke volume was significantly higher after 16 weeks of training. At 50% VO2max, heart rate and rate pressure product were lower after 16 weeks of training and at 70% VO2max, cycle ergometry power, VO2, and arterio-venous oxygen difference were higher after 16 weeks of training. Leg strength significantly increased after 16 weeks of training.",
            "output": [
                "Does resistance training reduce the blood pressure response of older men during submaximum aerobic exercise?"
            ]
        },
        {
            "id": "task847-7920b23eb411434db8646d08ae179603",
            "input": "Cervical cancer caused by the human papilloma virus (HPV) continues to be the cause of yearly death among women. However, it is a curable disease when diagnosed at an early stage. Recently, several researches have reported that heat shock protein (HSP) 60, a chaperone protein of molecular weight of 60 kDa, is involved in carcinogenesis and apoptosis. In order to evaluate the prognostic significance of HSP60 in cervical cancer, we examined differences in the HSP60 expression between cervical cancer and normal tissues in women.', 'Tissue samples were collected from 20 cervical cancer patients and 20 normal controls. HSP60 expression of cervical cancer and normal tissues were verified by the 2D gel proteomics, semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analyses.', 'In 2D proteomic analysis, an increase of HSP60 expression was detected in cervical cancer tissues and confirmed by Western blot analysis (p < 0.05). However, messenger RNA (mRNA) levels of HSP60 did not display any significant differences between cervical cancer and normal tissues.",
            "output": [
                "Is expression of heat shock protein 60 kDa upregulated in cervical cancer?"
            ]
        },
        {
            "id": "task847-05e2a12b60794ea88b6b7a1800b8861a",
            "input": "Asthma is a multi-factorial inflammatory disease associated with increased oxidative stress and altered antioxidant defences. We have evaluated the effect of choline on oxidative stress in a mouse model of airway disease.', 'Balb/c mice were sensitised with 100 microg of ovalbumin on days 0 and 14, and challenged with aerosolized ovalbumin on days 25-27. Mice were administered 1 mg kg(-1) of choline via oral gavage or intranasal route on days 14-27. Mice were also administered 100 mg kg(-1) of alpha-lipoic acid as standard antioxidant. Total cell counts, eosinophils and eosinophil peroxidase (EPO) activity were determined in bronchoalveolar lavage (BAL) fluid. Reactive oxygen species (ROS), lipid peroxidation and isoprostanes levels were measured in BAL fluid. IL-13 and tumour necrosis factor-alpha (TNF-alpha) levels were also measured in BAL fluid and spleen cell culture supernatant. Nuclear factor kappaB (NFkappaB) p65 protein expression was measured after last ovalbumin challenge in nuclear and cytosolic extracts of lungs.', 'Compared with ovalbumin-challenged mice, choline and alpha-lipoic acid treated mice had significantly reduced eosinophilic infiltration and EPO activity in BAL fluid. Choline and alpha-lipoic acid treatment reduced ROS production and isoprostanes level significantly in BAL fluid and thus suppressed oxidative stress. Choline and alpha-lipoic acid administration by either route decreased lipid peroxidation levels and down regulated NFkappaB activity. Further, choline and/or alpha-lipoic acid treatment suppressed TNF-alpha level significantly as compared with that of ovalbumin-challenged mice.",
            "output": [
                "Does choline supplementation reduce oxidative stress in mouse model of allergic airway disease?"
            ]
        },
        {
            "id": "task847-ae06e88eb98e4c3898bd136536ac32f0",
            "input": "To study the prevalence and age dependency of senile plaques (SP) and neurofibrillary tangles (NFT), the brain changes characteristic of Alzheimer disease (AD), and their association with apolipoprotein E (APOE) genotypes in a community-dwelling normal population.', 'This neuropathological study used both silver staining and A beta immunohistochemistry in brain tissue microarrays, including SP coverage and NFT counts from frontal cortex and hippocampus, and APOE genotyping, and was performed on a consecutive prospective series of 603 subjects (aged between 0 and 97 years) of an unselected population living outside of institutions. Cases were subjected to autopsy following sudden or unexpected out-of-hospital death, covering 22.1% of the mortality of Tampere, Finland and its surroundings. None died of AD, although 22 (3.7%) were demented and 10 (1.7%) had memory problems.', 'Of the series, 30.8% had SP, and 42.1% had NFT; these occurred more commonly among females and showed a strong relationship with age. Both changes had already appeared at around 30 years of age, reaching an occurrence of almost 100% in the oldest. SP were more frequent in APOE epsilon 4-carriers compared with noncarriers in every age group except the oldest (>90 years). The difference was most evident during the ages 50 to 59 years, where 40.7% of epsilon 4-carriers had SP, compared with 8.2% in noncarriers (odds ratio, 8.39; 95% confidence interval, 2.55-27.62). The difference in NFT prevalence between APOE genotypes was not statistically significant in any age group.",
            "output": [
                "Does apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begin in middle age?"
            ]
        },
        {
            "id": "task847-93830a73a1154c84b0f3d7fbd0c4214b",
            "input": "Structural abnormalities of the anterior cingulate cortex (ACC) may interfere with the interaction of cortical and limbic networks involved in emotional regulation and contribute to chronic depressive syndromes in the elderly. This study examined the relationship of regional anterior cingulate cortical volumes with treatment remission of elderly depressed patients. We hypothesized that patients who failed to remit during a 12-week controlled treatment trial of escitalopram would exhibit smaller anterior cingulate gray matter volumes than patients who remitted.', 'The participants were 41 non-demented individuals with non-psychotic major depression. After a 2-week single-blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for at least 2 consecutive weeks. The patient sample consisted of 22 depressed patients who achieved remission during the study and 19 depressed patients who remained symptomatic. High-resolution magnetization-prepared rapidly acquired gradient echo (MPRAGE) sequences were acquired on a 1.5 T scanner and regional ACC volumes were manually outlined (dorsal, rostral, anterior subgenual, and posterior subgenual).', 'Repeated measure analyses revealed that patients who failed to remit following escitalopram treatment had smaller dorsal and rostral anterior cingulate gray matter volumes than patients who remitted, whereas subgenual cortical volumes did not differ between the groups.",
            "output": [
                "Do anterior cingulate cortical volumes and treatment remission of geriatric depression?"
            ]
        },
        {
            "id": "task847-0ea8759b4a44479eb539529619224587",
            "input": "To survive and reproduce, animals must be able to modify their motor behavior in response to changes in the environment. We studied a complex behavior of Caenorhabditis elegans, male mating behavior, which provided a model for understanding motor behaviors at the genetic, molecular as well as circuit level. C. elegans male mating behavior consists of a series of six sub-steps: response to contact, backing, turning, vulva location, spicule insertion, and sperm transfer. The male tail contains most of the sensory structures required for mating, in addition to the copulatory structures, and thus to carry out the steps of mating behavior, the male must keep his tail in contact with the hermaphrodite. However, because the hermaphrodite does not play an active role in mating and continues moving, the male must modify his tail posture to maintain contact. We provide a better understanding of the molecular and neuro-muscular pathways that regulate male tail posture during mating.', 'Genetic and laser ablation analysis, in conjunction with behavioral assays were used to determine neurotransmitters, receptors, neurons and muscles required for the regulation of male tail posture. We showed that proper male tail posture is maintained by the coordinated activity of opposing muscle groups that curl the tail ventrally and dorsally. Specifically, acetylcholine regulates both ventral and dorsal curling of the male tail, partially through anthelmintic levamisole-sensitive, nicotinic receptor subunits. Male-specific muscles are required for acetylcholine-driven ventral curling of the male tail but dorsal curling requires the dorsal body wall muscles shared by males and hermaphrodites. Gamma-aminobutyric acid activity is required for both dorsal and ventral acetylcholine-induced curling of the male tail and an inhibitory gamma-aminobutyric acid receptor, UNC-49, prevents over-curling of the male tail during mating, suggesting that cross-inhibition of muscle groups helps maintain proper tail posture.",
            "output": [
                "Does coordination of opposing sex-specific and core muscle groups regulate male tail posture during Caenorhabditis elegans male mating behavior?"
            ]
        },
        {
            "id": "task847-47bb0e9b4d3d4bb9813989647e02079e",
            "input": "Dysfunctions in the serotonergic system have been implicated in several neurological disorders such as depression. Elderly individuals who have been diagnosed with clinical depression show elevated cases of neurodegenerative diseases. This has led to suggestions that modulating the serotonin (5-HT) system could provide an alternative method to current therapies for alleviating these pathologies. The neuroprotective effects of bilobalide in vitro have been documented. We aim to determine whether bilobalide affects the 5-HT system in the nematode C. elegans. The wild type worms, as well as well-characterized 5-HT mutants, were fed with bilobalide in a range of concentrations, and several 5-HT controlled behaviors were tested.', 'We observed that bilobalide significantly inhibited 5-HT-controlled egg-laying behavior in a dose-dependent manner, which was blocked in the 5-HT receptor mutants (ser-4, mod-1), but not in the 5-HT transporter (mod-5) or synthesis (tph-1) mutants. Bilobalide also potentiated a 5-HT-controlled, experience-dependent locomotory behavior, termed the enhanced slowing response in the wild type animals. However, this effect was fully blocked in 5-HT receptor mod-1 and dopamine defective cat-2 mutants, but only partially blocked in ser-4 mutants. We also demonstrated that acetylcholine transmission was inhibited in a transgenic C. elegans strain that constitutively expresses Abeta, and bilobalide did not significantly affect this inhibition.",
            "output": [
                "Does bilobalide modulate serotonin-controlled behaviors in the nematode Caenorhabditis elegans?"
            ]
        },
        {
            "id": "task847-5a976693761a426eb740ff9fd8af36f4",
            "input": "Atrial natriuretic peptide (ANP) is a hormone that has both antihypertrophic and antifibrotic properties in the heart. We hypothesized that myocyte-derived ANP inhibits endothelin (ET) gene expression in fibroblasts.', 'We have investigated the mechanism(s) involved in the antiproliferative effect of ANP on cardiac fibroblasts in a cell culture model. We found that cardiac myocytes inhibited DNA synthesis in co-cultured cardiac fibroblasts as did treatment with the ET-1 antagonist BQ610. The effect of co-culture was reversed by antibody directed against ANP or the ANP receptor antagonist HS-142-1. ANP inhibited the expression of the ET-1 gene and ET-1 gene promoter activity in cultured fibroblasts. The site of the inhibition was localized to a GATA-binding site positioned between -132 and -135 upstream from the transcription start site. GATA4 expression was demonstrated in cardiac fibroblasts, GATA4 bound the ET-1 promoter both in vitro and in vivo, and siRNA-mediated knockdown of GATA4 inhibited ET-1 expression. ET-1 treatment resulted in increased levels of phospho-serine(105) GATA4 in cardiac fibroblasts and this induction was partially suppressed by co-treatment with ANP.",
            "output": [
                "Does atrial natriuretic peptide suppress endothelin gene expression and proliferation in cardiac fibroblasts through a GATA4-dependent mechanism?"
            ]
        },
        {
            "id": "task847-be8ac7c446b0445a847f9c1ebb9fff08",
            "input": "Hydrogen peroxide is enzymatically processed by catalase, and catalase deficiency in blood is known as acatalasemia. We examined whether low catalase activity is a risk factor for diabetes mellitus.', 'Blood glucose, insulin and glucose tolerance test were examined in acatalasemic and normal mice under non-stress and oxidative stress conditions. Alloxan administration was used as oxidative stress.', 'Alloxan, which was a drug that caused diabetes mellitus, mostly generated hydrogen peroxide by the reaction of alloxan and reduced glutathione, in vitro. Incidence of hyperglycemia in alloxan-untreated acatalasemic mice was as low as that in the normal mice. However, the incidence of acatalasemia mice treated with alloxan was higher than that in normal mice, and the number of pancreatic beta-cells in the acatalasemic mice was less than that in normal mice.",
            "output": [
                "Is low catalase activity in blood associated with the diabetes caused by alloxan?"
            ]
        },
        {
            "id": "task847-4c4784ca8c544b5594b022636da083ac",
            "input": "Formulation of DNA/cationic lipid complexes (lipoplexes) designed for nucleic acid delivery mostly results in positively charged particles which are thought to enter cells by endocytosis. We recently developed a lipoplex formulation called Neutraplex that allows preparation of both cationic and anionic stable complexes with similar lipid content and ultrastructure.', 'To assess whether the global net charge could influence cell uptake and activity of the transported oligonucleotides (on), we prepared lipoplexes with positive and negative charges and compared: (i) their physicochemical properties by zeta potential analysis and dynamic light scattering, (ii) their cell uptake by fluorescence microscopy and flow cytometry, and (iii) the biological activity of the transported ON using a splicing correction assay. We show that positively or negatively charged lipoplexes enter cells cells using both temperature-dependent and -independent uptake mechanisms. Specifically, positively charged lipoplexes predominantly use a temperature-dependent transport when cells are incubated OptiMEM medium. Anionic lipoplexes favour an energy-independent transport and show higher ON activity than cationic lipoplexes in presence of serum. However, lipoplexes with high positive global net charge and OptiMEM medium give the highest uptake and ON activity levels.",
            "output": [
                "Do physico-chemical characteristics of lipoplexes influence cell uptake mechanisms and transfection efficacy?"
            ]
        },
        {
            "id": "task847-70573ce78ada43fea8ba3776b11d8d56",
            "input": "In mice, a subpopulation of gut dendritic cells (DCs) expressing CD103 drives the development of regulatory T (T(reg)) cells. Further, it was recently described that the cross-talk between human intestinal epithelial cells (IECs) and DCs helps in maintaining gut immune homeostasis via the induction of non-inflammatory DCs. In this study, an analysis was carried out to determine whether IECs could promote the differentiation of CD103+ tolerogenic DCs, and the function of primary CD103+ DCs isolated from human mesenteric lymph nodes (MLNs) was evaluated.', \"Monocyte-derived DCs (MoDCs) and circulating CD1c+ DCs were conditioned or not with supernatants from Caco-2 cells or IECs isolated from healthy donors or donors with Crohn's disease and analysed for their ability to induce T(reg) cell differentiation. In some cases, transforming growth factor beta (TGFbeta), retinoic acid (RA) or thymic stromal lymphopoietin (TSLP) were neutralised before conditioning. CD103+ and CD103- DCs were sorted by fluorescence-activated cell sorting (FACS) from MLNs and used in T(reg) cell differentiation experiments.\", \"It was found that human IECs promoted the differentiation of tolerogenic DCs able to drive the development of adaptive Foxp3+ T(reg) cells. This control was lost in patients with Crohn's disease and paralleled a reduced expression of tolerogenic factors by primary IECs. MoDCs differentiated with RA or IEC supernatant upregulated the expression of CD103. Consistently, human primary CD103+ DCs isolated from MLNs were endowed with the ability to drive T(reg) cell differentiation. This subset of DCs expressed CCR7 and probably represents a lamina propria-derived migratory population.",
            "output": [
                "Do human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells?"
            ]
        },
        {
            "id": "task847-470b592aaad04da189aba0c59d2a0685",
            "input": "Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption. This bacterium exerts its pathogenic effect indirectly through multiple virulence factors, such as lipopolysaccharides, fimbriae, and proteases. Another possible pathogenic path may be through a direct interaction with the host's soft and hard tissues (e.g., alveolar bone), which could lead to periodontitis.\", 'The aim of the present study was to investigate the direct effect of live and heat-inactivated P gingivalis on bone resorption, using an in vitro osteoblast culture model.', 'Optical microscopy and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide MTT assay revealed that live P gingivalis induced osteoblast detachment and reduced their proliferation. This effect was specific to live bacteria and was dependent on their concentration. Live P gingivalis increased IL-6 mRNA expression and protein production and downregulated RANKL and OPG mRNA expression. The effect of live P gingivalis on bone resorption was strengthened by an increase in MMP-9 expression and its activity. This increase was accompanied by an increase in TIMP-1 and TIMP-2 mRNA expression and protein production by osteoblasts infected with live P gingivalis.",
            "output": [
                "Does porphyromonas gingivalis decrease osteoblast proliferation through IL-6-RANKL/OPG and MMP-9/TIMPs pathways?"
            ]
        },
        {
            "id": "task847-550a203bfde0450cb05c30dcd657e8c8",
            "input": "High-resolution CT (HRCT) scanning is part of the management of severe asthma, but its application varies between centers. We sought to describe the HRCT scan abnormalities of a large severe asthma cohort and to determine the utility of clinical features to direct the use of HRCT scanning in this group of patients.', 'Subjects attending our Difficult Asthma Clinic (DAC) between February 2000 and November 2006 (n = 463) were extensively re-characterized and 185 underwent HRCT scan. The HRCT scans were analyzed qualitatively and the interobserver variability was assessed. Using logistic regression we defined clinical parameters that were associated with bronchiectasis (BE) and bronchial wall thickening (BWT) alone or in combination.', 'HRCT scan abnormalities were present in 80% of subjects and often coexisted with BWT (62%), BE (40%), and emphysema (8%). The interobserver agreement for BE (kappa = 0.76) and BWT (kappa = 0.63) was substantial. DAC patients who underwent HRCT scanning compared with those who did not were older, had longer disease duration, had poorer lung function, were receiving higher doses of corticosteroids, and had increased neutrophilic airway inflammation. The sensitivity and specificity of detecting BE clinically were 74% and 45%, respectively. FEV(1)/FVC ratio emerged as an important predictor for both BE and BWT but had poor discriminatory utility for subjects who did not have airway structural changes (FEV(1)/FVC ratio, >or= 75%; sensitivity, 67%; specificity, 65%).",
            "output": [
                "Does qualitative analysis of high-resolution CT scan in severe asthma?"
            ]
        },
        {
            "id": "task847-61f5c60262074e94ba5b861e730d9116",
            "input": "Disseminated intravascular coagulation (DIC) is a complex systemic thrombohemorrhagic disorder involving intravascular coagulation and hemorrhage. The aim of this study is to test whether static magnetic field (SMF) is effective in attenuating lipopolysaccharide (LPS)-induced DIC.', 'In vivo experiments were performed in this study using male BALB/cByJ mice. An intraperitoneal injection of 50 mg/kg LPS was shown to lead to approximately 50% mortality and this dose was used in subsequent experiments. To test the effects of SMF on the survival rate of LPS-induced animals, the mice were exposed to 0.25-T SMF for 2 h before LPS injection. In addition, the effect of a 2-h SMF treatment on the production of anti-inflammatory cytokines was evaluated.', 'In the first set of experiments, we found that the survival rate was higher in the SMF-exposed group than in the sham-exposed group. The circulating platelet (PLT) counts in the SMF-exposed mice were significantly higher than in the unexposed animals. However, no significant changes in inflammatory cytokine, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6) and monocyte chemotactic protein 1 (MCP-1), in plasma were found after SMF treatment. The results from the second experiment showed that the plasma levels of interleukin-1 receptor antagonist (IL-1ra) were higher in the SMF-exposed group than in the sham group.",
            "output": [
                "Does static magnetic field attenuate mortality rate of mice by increasing the production of IL-1 receptor antagonist?"
            ]
        },
        {
            "id": "task847-4ed102eb847b4184ac8b2967975b7ca5",
            "input": "The mammalian target of Rapamycin (mTOR) kinase plays a key role in translational control of a subset of mRNAs through regulation of its initiation step. In neurons, mTOR is present at the synaptic region, where it modulates the activity-dependent expression of locally-translated proteins independently of mRNA synthesis. Indeed, mTOR is necessary for different forms of synaptic plasticity and long-term memory (LTM) formation. However, little is known about the time course of mTOR activation and the extracellular signals governing this process or the identity of the proteins whose translation is regulated by this kinase, during mnemonic processing.', 'Here we show that consolidation of inhibitory avoidance (IA) LTM entails mTOR activation in the dorsal hippocampus at the moment of and 3 h after training and is associated with a rapid and rapamycin-sensitive increase in AMPA receptor GluR1 subunit expression, which was also blocked by intra-hippocampal delivery of GluR1 antisense oligonucleotides (ASO). In addition, we found that pre- or post-training administration of function-blocking anti-BDNF antibodies into dorsal CA1 hampered IA LTM retention, abolished the learning-induced biphasic activation of mTOR and its readout, p70S6K and blocked GluR1 expression, indicating that BDNF is an upstream factor controlling mTOR signaling during fear-memory consolidation. Interestingly, BDNF ASO hindered LTM retention only when given into dorsal CA1 1 h after but not 2 h before training, suggesting that BDNF controls the biphasic requirement of mTOR during LTM consolidation through different mechanisms: an early one involving BDNF already available at the moment of training, and a late one, happening around 3 h post-training that needs de novo synthesis of this neurotrophin.",
            "output": [
                "Does bDNF activate mTOR to regulate GluR1 expression required for memory formation?"
            ]
        },
        {
            "id": "task847-06f0ae08718d45b5a2166248d3c4b6b1",
            "input": "The hypoxia-inducible transcription factor (HIF) subunits are destabilized via the O(2)-dependent prolyl hydroxylase domain proteins (PHD1, PHD2, and PHD3). We investigated whether inhibition of PHDs via upregulating HIF might promote postischemic neovascularization.', 'Mice with right femoral artery ligation were treated, by in vivo electrotransfer, with plasmids encoding for an irrelevant short hairpin RNA (shRNA) (shCON [control]) or specific shRNAs directed against HIF-1alpha (shHIF-1alpha), PHD1 (shPHD1), PHD2 (shPHD2), and PHD3 (shPHD3). The silencing of PHDs induced a specific and transient downregulation of their respective mRNA and protein levels at day 2 after ischemia and, as expected, upregulated HIF-1alpha. As a consequence, 2 key hypoxia-inducible proangiogenic actors, vascular endothelial growth factor-A and endothelial nitric oxide synthase, were upregulated at the mRNA and protein levels. In addition, monocyte chemotactic protein-1 mRNA levels and infiltration of Mac-3-positive macrophages were enhanced in ischemic leg of mice treated with shPHD2 and shPHD3. Furthermore, activation of HIF-1alpha-related pathways was associated with changes in postischemic neovascularization. At day 14, silencing of PHD2 and PHD3 increased vessel density by 2.2- and 2.6-fold, capillary density by 1.8- and 2.1-fold, and foot perfusion by 1.2- and 1.4-fold, respectively, compared with shCON (P<0.001). shPHD1 displayed a lower proangiogenic effect. Of interest, coadministration of shHIF-1alpha with shPHD3 abrogated shPHD3-related effects, suggesting that activation of endogenous HIF-1-dependent pathways mediated the proangiogenic effects of PHD silencing.",
            "output": [
                "Does inhibition of prolyl hydroxylase domain proteins promote therapeutic revascularization?"
            ]
        },
        {
            "id": "task847-408f59ddddcd4bdbae82ce9405529299",
            "input": "During endoscopic or open carpal tunnel release, a palmar fat pad is visualized immediately proximal to the distal end of the transverse carpal ligament (TCL). Visualization of the fat pad allows anticipation of complete release of the TCL without unnecessary distal dissection that could risk iatrogenic injury. This study defines the anatomic relationship of the distal edge of the TCL to the fat pad, the superficial palmar arch, and the motor branch of the median nerve.', 'Eighteen fresh-frozen cadaver hands were dissected, and the proximal aspect of the palmar fat pad, the distal edge of the TCL, the superficial palmar arch, and the motor branch of the median nerve were identified. An electronic caliper was used to measure distances between each structure along the axis of the radial border of the ring finger. A subset of 8 hands was radiographically imaged with fingers flexed and extended (wrist neutral) to determine if finger positioning influenced measurements between marked structures.', 'The proximal aspect of the palmar fat pad is 2.0 mm proximal to the distal edge of the TCL. The distal end of the TCL, as measured along the axis of the radial border of the ring finger is 12.7 mm from the most proximal aspect of the palmar arch and 6.5 mm from the nearest aspect of the motor branch. Flexing the fingers decreases the distance between the distal end of the TCL and the fat pad while not markedly affecting the distance between the TCL and the palmar arch or the motor branch.",
            "output": [
                "Is the palmar fat pad a reliable intraoperative landmark during carpal tunnel release?"
            ]
        },
        {
            "id": "task847-f061e5657711456fbd1ce1e3129fb1db",
            "input": "The goal was to evaluate polymorphisms of the APOE gene as modifiers of neurobehavioral outcomes for preschool-aged children with congenital heart defects, after cardiac surgery.', 'A prospective observational study with neurodevelopmental evaluation between the fourth and fifth birthdays was performed. Attention and behavioral skills were assessed through parental report.', 'Parents of 380 children completed the neurobehavioral measures. Child Behavior Checklist scores for the pervasive developmental problem scale were in the at-risk or clinically significant range for 15% of the cohort, compared with 9% for the normative data (P < .00001). Attention problem scores were in the at-risk or clinically significant range for 12% of the cohort, compared with 7% for the normative data (P = .0002). The Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Preschool Version, was completed for 378 children; 30% scored in the clinically significant range for inattention and 22% for impulsivity. After adjustment for covariates, the APOE epsilon2 allele was significantly associated with higher scores (worse problems) for multiple Child Behavior Checklist indices, including somatic complaints (P = .009), pervasive developmental problems (P = .032), and internalizing problems (P = .009). In each case, the epsilon4 allele was associated with a better outcome. APOE epsilon2 carriers had impaired social skills, compared with epsilon4 carriers (P = .009).",
            "output": [
                "Does apolipoprotein E genotype modify the risk of behavior problems after infant cardiac surgery?"
            ]
        },
        {
            "id": "task847-ea91c7e09ab544a9b48b31d45153fac6",
            "input": "Zinc-alpha2-glycoprotein (ZAG) is a novel adipokine, which may act locally to influence adipocyte metabolism. This study assessed the effect of increased adiposity on ZAG expression in adipose tissue in human subjects. The study also examined the association between ZAG and adiponectin expression in human adipose tissue, and whether ZAG modulates adiponectin secretion by human adipocytes.', 'Adipose tissue (visceral and subcutaneous) was collected from human subjects with a wide range of BMIs. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were used for in vitro studies. ZAG mRNA levels were quantified by real-time PCR and protein by Western blotting.', 'In human subjects, ZAG mRNA level was negatively correlated with BMI (r = -0.61, P < 0.001, n = 23, visceral; r = -0.6, P < 0.05, n = 14, subcutaneous) and fat mass (r = -0.62, P < 0.01, visceral; r = -0.6, P < 0.05, subcutaneous). Negative associations were also found between ZAG mRNA and insulin resistance parameters including plasma insulin (r = -0.65, P < 0.001, visceral; r = -0.55, P < 0.05, subcutaneous) and homeostasis model of insulin resistance (HOMA-IR) (r = -0.65, P < 0.001, visceral; r = -0.52, P = 0.055, subcutaneous), and C reactive protein (CRP) (r = -0.46, P < 0.05, visceral; r = -0.53, P < 0.05, subcutaneous). However, ZAG mRNA was positively correlated with adiponectin (r = 0.5, P < 0.05, visceral; r = 0.82, P < 0.001, subcutaneous) but negatively associated with leptin mRNA (r = -0.42, P < 0.05, visceral; r = -0.54, P < 0.05, subcutaneous). ZAG secretion by differentiated human adipocytes was abundant. Addition of recombinant ZAG stimulated adiponectin release from human adipocytes.",
            "output": [
                "Is the adipokine zinc-alpha2-glycoprotein ( ZAG ) downregulated with fat mass expansion in obesity?"
            ]
        },
        {
            "id": "task847-77fce0b2e6f8461986b89935c5ce2111",
            "input": "Thyroid hormone impacts on the cardiovascular system. (Subclinical) hyperthyroidism results in sympathovagal imbalance due to decreased vagal tone. However, conflicting data have been reported on the effects of hypothyroidism on the activity of the autonomic nervous system (ANS). In hypothyroidism, both increased and decreased sympathetic activity and increased vagal tone have been found.', 'To study the effects of acute short-term overt hypothyroidism and thyroxine replacement therapy on the ANS by measuring urinary excretion of catecholamines and heart rate variability (HRV).', 'Prospective study.', 'University hospital.', 'We studied 11 patients, previously treated with thyroidectomy for differentiated thyroid carcinoma, during hypothyroidism caused by cessation of thyroxine substitution for 4 weeks and during thyroxine replacement therapy, and 21 matched healthy controls.', 'The activity of the ANS was assessed by measuring urinary excretion of catecholamines and HRV at rest and during a challenge of the ANS by a mental stress test.', 'Urinary dopamine excretion was significantly lower during hypothyroidism. Although in the patients total variability was unchanged, HRV analysis showed a significantly lower low frequency/high frequency ratio, indicating sympathovagal imbalance with sympathetic withdrawal. The mental stress test in the patients resulted in a significant increase in heart rate to the extent of 16-18%. This response was not different between the hypothyroid state and during thyroxine replacement therapy suggesting that cardiovascular reflexes in these patients remain intact.",
            "output": [
                "Does short-term overt hypothyroidism induce sympathovagal imbalance in thyroidectomized differentiated thyroid carcinoma patients?"
            ]
        },
        {
            "id": "task847-caec5fcb3d0649a296cccd34329b9f8d",
            "input": "Tuberculosis (TB) is the largest cause of death in human immunodeficiency virus type 1 (HIV-1) infection, having claimed an estimated one third to one half of the 30 million AIDS deaths that have occurred worldwide. Different strains of Mycobacterium tuberculosis (MTb), the causative agent of TB, are known to modify the host immune response in a strain-specific manner. However, a MTb strain-specific impact upon the regulation of HIV-1 replication has not previously been established.', '[corrected] We isolated normal human peripheral blood mononuclear cells (PBMC) and co-infected them with HIV-1 and with either the well characterized CDC1551 or HN878 MTb clinical isolate. We show that HIV-1 co-infection with the CDC1551 MTb strain results in higher levels of virus replication relative to co-infection with the HN878 MTb strain ex vivo. Furthermore, we show that the distinct pattern of CDC1551 or HN878 induced HIV-1 replication is associated with significantly increased levels of TNF and IL-6, and of the transcription and nuclear translocation of the p65 subunit of the transcription factor NF-kappaB, by CDC1551 relative to HN878.",
            "output": [
                "Is hIV-1 replication differentially regulated by distinct clinical strains of Mycobacterium tuberculosis?"
            ]
        },
        {
            "id": "task847-e2917c7d12eb4d95b1abf5efb117e392",
            "input": "To determine the prevalence of fathers' attendance at pretest cancer genetic counseling sessions with mothers undergoing BRCA1/2 genetic testing for hereditary breast/ovarian cancer (HBOC) risk, and to identify psychosocial and other correlates of fathers' attendance.\", 'One hundred and twenty-one fathers of minor-age children who were spouses/partners of women (mothers) undergoing such counseling and testing were recruited, completed a behavioral self-report survey, and provided data about their sociodemographic backgrounds, father-child cancer communication histories, parenting relationship quality, and information-seeking and perceived knowledge.', 'A total of 27.3% of fathers attended pretest cancer genetic counseling with mothers. Compared to fathers who did not attend pretest cancer genetic counseling, those who did had stronger parenting alliances with mothers, were more likely to have sought out information about BRCA1/2 testing, and felt more informed about testing. In an adjusted logistic regression model of session attendance, the strength of the parenting alliance was associated with a 6% increase in the likelihood of attending genetic counseling (odds ratio [OR]=1.06, 95% confidence interval [CI]=1.01, 1.12, p<.05) and greater perceived knowledge about BRCA1/2 testing was associated with a four-fold increase in the likelihood of session attendance (OR=4.03, CI=1.77, 9.37, p<.001).",
            "output": [
                "Does prevalence and correlate of mothers and fathers attending pretest cancer genetic counseling together?"
            ]
        },
        {
            "id": "task847-5ac5495a2fc344499df7510d47986ede",
            "input": "Patients with acute myocardial infarction (AMI) whose culprit lesion lies in a branch of the 3 major coronary arteries have well-preserved cardiac function. A first MI with preserved cardiac function is a risk factor for left ventricular free wall rupture (LVFWR), so the aim of this study was to investigate the possible relationship between AMI with branch segment occlusion and LVFWR.', 'The 439 patients with AMI were retrospectively studied. They were divided into 2 groups: group B (n=70; segments 4 atrioventricular node artery, 4 posterior descending coronary artery, 8, 9, 10, 12, 14, or 15 according to the AHA classification), and group P (n=369; segments 1, 2, 3, 5, 6, 7, 11, or 13). Primary percutaneous coronary intervention (PCI) was more often performed in group P (75% vs 57%; P=0.0018). In-hospital mortality tended to be lower in group B (1.4% vs 6.2%; P=0.105). The incidence of LVFWR was significantly higher in group B (10.0% vs 1.6%; P=0.0002).By multivariate logistic regression analysis, 1-vessel disease, absence of primary PCI, branch segment occlusion, and age were identified as independent predictors of LVFWR.",
            "output": [
                "Is branch segment occlusion with acute myocardial infarction a risk for left ventricular free wall rupture?"
            ]
        },
        {
            "id": "task847-a051329701c64c159dda64bf33c6d3d7",
            "input": "Onychomycosis is a common cause of nail dystrophy and may be associated with tinea pedis. The presence of dermatophyte fungi in clinically normal nails is unknown.', 'To assess the presence of dermatophyte fungi in normal-appearing toenails and to compare the risk of subclinical dermatophytosis in patients without and with concurrent tinea pedis.', 'This is a prospective, University-based study of adults without and with microscopically confirmed tinea pedis. Subjects with dystrophy of any toenail were excluded, as were those ever previously diagnosed as having onychomycosis and those who had used topical antifungals in the past year. A great toenail clipping obtained from each subject was submitted for periodic acid-Schiff histology.', 'One hundred and one subjects (63 men and 38 women, mean +/- SD age 45.4 +/- 15.7 years) were included. Overall, septate hyphae (ostensibly dermatophyte) were identified in seven specimens. Of the 66 control subjects, one case (1.5%) of nail dermatophyte was identified. Of the 35 subjects with tinea pedis, six cases (17%) of nail dermatophyte were identified (P = 0.0066; odds ratio 13.4, 95% confidence interval 1.6-117). There were no significant differences in age or gender between the experimental and control groups or between the nail dermatophyte-positive and negative cohorts.",
            "output": [
                "Is subclinical onychomycosis associated with tinea pedis?"
            ]
        },
        {
            "id": "task847-6c19ac1988f54671a2b4d61716e01ccc",
            "input": "The normal anterior translation of the articular surface of the distal humerus with respect to the humeral diaphysis facilitates elbow flexion. We hypothesize that there is a correlation between anterior translation of the distal humeral articular surface and flexion after open reduction and internal fixation (ORIF) of a fracture of the distal humerus.', 'Two independent observers evaluated 141 lateral radiographs of patients more than 6 months after fracture of the distal humerus and 155 lateral radiographs of patients without injury of the distal humerus. The distance between the most anterior point of the distal humerus articular surface, perpendicular to the humeral shaft, from the anterior border of the distal part of the humeral diaphysis, was measured on lateral radiographs as a percentage of the width of the humeral shaft.', 'The technique of measuring anterior translation of the distal humeral articular surface had good intra- and interobserver reliability. The most anterior point of the distal humeral articular surface lies an average of 11.7 mm (range, 6.8 to 17.0 mm) in front of the most anterior border of the humeral shaft in normal distal humeri, which represents 62% of the humeral shaft diameter (range, 33% to 91%). There was a limited but significant correlation between flexion and anterior translation as a percentage of the humeral shaft diameter in distal humeri after fracture that was maintained in multivariable statistical models.",
            "output": [
                "Is loss of anterior translation of the distal humeral articular surface associated with decreased elbow flexion?"
            ]
        },
        {
            "id": "task847-1edd12e5e2c74b5095f1ca8e41a9e9a7",
            "input": "A lot of high-throughput studies produce protein-protein interaction networks (PPINs) with many errors and missing information. Even for genome-wide approaches, there is often a low overlap between PPINs produced by different studies. Second-level neighbors separated by two protein-protein interactions (PPIs) were previously used for predicting protein function and finding complexes in high-error PPINs. We retrieve second level neighbors in PPINs, and complement these with structural domain-domain interactions (SDDIs) representing binding evidence on proteins, forming PPI-SDDI-PPI triangles.', 'We find low overlap between PPINs, SDDIs and known complexes, all well below 10%. We evaluate the overlap of PPI-SDDI-PPI triangles with known complexes from Munich Information center for Protein Sequences (MIPS). PPI-SDDI-PPI triangles have ~20 times higher overlap with MIPS complexes than using second-level neighbors in PPINs without SDDIs. The biological interpretation for triangles is that a SDDI causes two proteins to be observed with common interaction partners in high-throughput experiments. The relatively few SDDIs overlapping with PPINs are part of highly connected SDDI components, and are more likely to be detected in experimental studies. We demonstrate the utility of PPI-SDDI-PPI triangles by reconstructing myosin-actin processes in the nucleus, cytoplasm, and cytoskeleton, which were not obvious in the original PPIN. Using other complementary datatypes in place of SDDIs to form triangles, such as PubMed co-occurrences or threading information, results in a similar ability to find protein complexes.",
            "output": [
                "Do triangle network motifs predict complexes by complementing high-error interactomes with structural information?"
            ]
        },
        {
            "id": "task847-79412294e5c74252ac6624c8bb2f9852",
            "input": "Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are both associated with insulin resistance.We assessed whether NAFLD is associated with impaired insulin sensitivity in PCOS women independently of age and total adiposity.', 'We enrolled 14 young PCOS women with NAFLD, 14 women with PCOS alone and 14 healthy controls, who were matched for age, body mass index, and total body fat (by bio-impedance analyzer). NAFLD was diagnosed by the surrogate measure of abnormal serum alanine aminotransferase (ALT) concentrations (defined as ALT>19 U/l) after excluding other secondary causes of liver disease (alcohol, virus, and medications). Insulin sensitivity was measured by euglycemic hyperinsulinemic clamp.', 'Insulin sensitivity was markedly decreased (p<0.001) in PCOS women with abnormal ALT levels, whereas it was similar between PCOS women with normal ALT levels andmatched healthy controls (8.3+/-2.5 vs 12.1+/-1.7 vs 13.2+/-1.8 mg/min x kg of fat-free mass, respectively). PCOS women with abnormal ALT levels also had higher plasma triglycerides and lower HDLcholesterol concentrations than those with PCOS alone. There was a strong inverse association between serum ALT levels and insulin sensitivity in the whole group of PCOS women (r=-0.59, p=0.0013).",
            "output": [
                "Are abnormal serum alanine aminotransferase levels associated with impaired insulin sensitivity in young women with polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-10de169a436f4c5184eced35bbe8ed5a",
            "input": "We have previously shown that the cardioprotective effect of ischemic preconditioning (IPC) is suppressed in hyperhomocysteinemic rat hearts. The present study investigated the effect of 2-chloro-N-cyclopentyladenosine (CCPA), a selective adenosine-A1 receptor agonist, in hyperhomocysteinemia-induced attenuation of the cardioprotective effect of IPC.', 'Rats were administered L-methionine (1.7 g/kg/day po) for 8 weeks to produce hyperhomocysteinemia. Isolated Langendorff perfused normal and hyperhomocysteinemic rat hearts were subjected to 30-minute global ischemia, followed by a 120-minute reperfusion. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase and CK-MB release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid reactive substance and reduced form of glutathione.', 'Ischemia and reperfusion (I/R) produced myocardial injury by increasing myocardial infarct size, elevating lactate dehydrogenase and CK-MB release in coronary effluent, decreasing coronary flow rate, and inducing oxidative stress in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with high oxidative stress. The IPC afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts. However, IPC-mediated myocardial protection against I/R injury was abolished in hyperhomocysteinemic rat hearts. Administration of CCPA did not alter the cardioprotective effect of IPC in normal rat hearts, but its administration markedly restored the cardioprotective effect of IPC in hyperhomocysteinemic rat hearts.",
            "output": [
                "Does adenosine-A1 receptors activation restore the suppressed cardioprotective effects of ischemic preconditioning in hyperhomocysteinemic rat hearts?"
            ]
        },
        {
            "id": "task847-ccb3e325411a47b78040b9f82e6a36d0",
            "input": "Previous studies regarding the outcome of laparoscopic cholecystectomy (LC) in men have reported inconsistent findings. We conducted this prospective study to test the hypothesis that the outcome of LC is worse in men than women.', 'Between 1997 and 2002, a total of 391 consecutive LCs were performed by a single surgeon at King Fahd Hospital of the University. We collected and analyzed data including age, gender, body mass index (kg/m(2)), the American Society of Anesthesiologists (ASA) class, mode of admission (elective or emergency), indication for LC (chronic or acute cholecystitis [AC]), comorbid disease, previous abdominal surgery, conversion to open cholecystectomy, complications, operation time, and length of postoperative hospital stay.', 'Bivariate analysis showed that both genders were matched for age, ASA class and mode of admission. The incidences of AC (P = 0.003) and comorbid disease (P = 0.031) were significantly higher in men. Women were significantly more obese than men (P < 0.001) and had a higher incidence of previous abdominal surgery (P = 0.017). There were no statistical differences between genders with regard to rates of conversion (P = 0.372) and complications (P = 0.647) and operation time (P = 0.063). The postoperative stay was significantly longer in men than women (P = 0.001). Logistic regression analysis showed that male gender was not an independent predictor of conversion (Odds ratio [OR] = 0.37 and P = 0.43) or complications (OR = 0.42, P = 0.42). Linear regression analysis showed that male gender was not an independent predictor of the operation time, but was associated with a longer postoperative stay (P = 0.02).",
            "output": [
                "Is male gender a risk factor for the outcome of laparoscopic cholecystectomy : a single surgeon experience?"
            ]
        },
        {
            "id": "task847-5b3541b81e0745a699c18931cf7ea21d",
            "input": "For the last one and a half decade, it has been found that platelet-derived growth factor (PDGF) promotes glial tumor growth through autocrine and paracrine loops, by expression of PDGFalpha receptor (PDGFRalpha) on glioma cells and PDGFbeta receptor (PDGFRbeta) on proliferating endothelial cells. However, studies on oligodendrogliomas, correlating expression of PDGF and its receptor with tumor grade and proliferative activity, through MIB-1 labeling index (LI) are relatively few as compared to astroglial counterpart.', 'Formalin-fixed paraffin-embedded tissues from 55 cases of oligodendrogliomas (34 World Health Organization [WHO] grade II and 21 WHO grade III tumors) were subjected to immunohistochemistry. MIB-1 LI was calculated, and a semiquantitative scoring system for expression of PDGF and PDGFRalpha was used.', 'MIB-1 LI and PDGF expression increased with histologic grades of malignancy (\"t\" test, P < .001 and Mann Whitney test, U = 109, P < .001 respectively). The PDGF expression scores had a positive correlation with MIB-1 LI, irrespective of tumor grade (Pearson\\'s correlation coefficient, r = 0.566; P < .001). However, there was no significant difference of PDGFRalpha expression between 2 grades of tumors.",
            "output": [
                "Does platelet-derived growth factor expression correlate with tumor grade and proliferative activity in human oligodendrogliomas?"
            ]
        },
        {
            "id": "task847-50bd0de59bfb4dd7b85b97ca72c220ef",
            "input": "This study was undertaken to determine the survival benefit of extending resections to obtain microscopically negative margins after positive intraoperative frozen sections.', 'The impact of residual microscopic disease after pancreaticoduodenectomy is currently a point of controversy. It is, however, generally believed that microscopically positive margins negatively impact survival and this may be improved by ultimately achieving negative margins.', 'Since 1995, patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma have been prospectively followed. Margin status has been codified as macro/microscopically negative (R0) or macroscopically negative/microscopically positive (R1). The impact of margin status on survival was evaluated utilizing survival curve analysis. Data are presented as median, mean +/- SD where appropriate.', 'For pancreatic adenocarcinoma, 202 patients underwent pancreaticoduodenectomy. R0 resections were achieved in 158 patients, 17 of whom required extended resections to achieve complete tumor extirpation after an initially positive intraoperative frozen section (R1 --> R0). R1 resections were undertaken in 44 patients. Median survival for patients undergoing R0 resections was 21 months, 26 +/- 23.4 months versus 13 months, 17 +/- 21.0 months for patients undergoing R1 resections (P = 0.02). Median survival for patients undergoing R1 --> R0 resections was 11 months, 16 +/- 17.3, (P = 0.001). Margin status had a significant correlation with \"N\" stage and AJCC stage but not \"T\" stage.",
            "output": [
                "Is survival after pancreaticoduodenectomy improved by extending resections to achieve negative margins?"
            ]
        },
        {
            "id": "task847-9d657d2870cf46e99cb384136a18343a",
            "input": "The purpose of this study was to investigate the ability of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and their combination in predicting the duration and severity of acute kidney injury (AKI) after cardiac surgery in adults.', 'Using data from a prospective observational study of 100 adult cardiac surgical patients, we correlated early postoperative concentrations of plasma NGAL and serum cystatin C with the duration (time during which AKI persisted according to the Acute Kidney Injury Network criteria) and severity of AKI (change in serum creatinine) and with length of stay in intensive care.', 'We found a mean AKI duration of 67.2 +/- 41.0 hours which was associated with prolonged hospitalization (p < 0.001). NGAL, cystatin C, and their combination on arrival in intensive care correlated with subsequent AKI duration (all p < 0.01) and severity (all p < 0.001). The area under the receiver operating characteristic curve for AKI prediction was 0.77 (95% confidence interval: 0.63 to 0.91) for NGAL and 0.76 (95% confidence interval: 0.61 to 0.91) for cystatin C on arrival in intensive care. Both markers also correlated with length of stay in intensive care (p = 0.037; p = 0.001). Neutrophil gelatinase-associated lipocalin and cystatin C were independent predictors of AKI duration and severity and of length of stay in intensive care (all p < 0.05). The value of cystatin C on arrival in intensive care appeared to be due to a carry-over effect from preoperative values.",
            "output": [
                "Do novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults?"
            ]
        },
        {
            "id": "task847-013f8c2f26ae44cda393687928557ff0",
            "input": "Many patients require temporary inotropic support after cardiac surgery, and dobutamine is one of the commonly used drugs for this purpose. However, dobutamine infusion is frequently associated with unwanted sinus tachycardia. Selective sinus node electrical vagal stimulation through a discrete epicardial ganglionic plexus (fat pad) approach can achieve sinus rate slowing. Because sinus node fat pad vagal stimulation (SNFP-VS) can easily be applied during or after cardiac surgery, we hypothesized that combining selective SNFP-VS with dobutamine could produce desired hemodynamic improvement while avoiding sinus tachycardia in patients when inotropic drug support is needed.', 'This exploratory experimental study was performed in 7 open-chest dogs. Dobutamine (2.5 to 10 microg x kg(-1) x min(-1)) was infused at a rate producing at least 30% increase in sinus rate and cardiac output. Then electrical SNFP-VS was applied in the epicardial ganglionic plexus located at the right pulmonary vein-atrial junction, to slow the sinus rate back to control level. Hemodynamic data during control, with steady-state dobutamine infusion, and with dobutamine plus SNFP-VS were collected and compared.', 'Dobutamine significantly increased heart rate, systolic and diastolic blood pressures, peak left ventricular systolic pressure, positive and negative maximal derivatives of left ventricular pressure, and cardiac output. Combining SNFP-VS with dobutamine eliminated sinus rate increase while preserving all major hemodynamic benefits. Selective SNFP-VS itself had no direct effect on cardiac contractility during atrial pacing.",
            "output": [
                "Does cardiac vagal stimulation eliminate detrimental tachycardia effects of dobutamine used for inotropic support?"
            ]
        },
        {
            "id": "task847-881ddfb044f4490d89cacc9b8e0507f2",
            "input": "Limited data are available regarding the impact of caloric restriction (CR) in combination with resistance training (RT) on the metabolic profile of postmenopausal women.', 'The objective of the study was to determine whether RT adds to CR in improving body composition and the metabolic profile.', 'This was a 6-month, randomized, clinical trial.', 'Patients included 107 postmenopausal women (body mass index >27 kg/m(2)).', 'The intervention was a 6-month CR alone or in combination with a RT program.', 'Fat mass (FM), lean body mass (LBM), abdominal sc fat and visceral fat, fasting lipids, insulin sensitivity, resting blood pressure, and inflammation markers were measured.', 'Both groups were similar at baseline and significantly decreased body weight, body mass index, FM, percent FM, abdominal sc fat, and visceral fat after the study (P < 0.001), with greater losses of percent FM and trunk FM in the CR + RT group (P < 0.05). LMB significantly decreased in the CR (-0.9 +/- 2.4 kg) and the CR+RT (-0.4 +/- 2.2 kg) groups (P < 0.005), with no difference between them. Both groups significantly improved plasma triglycerides, fasting insulin level, glucose disposal, and markers of the inflammation profile after weight loss (P < 0.05), with no difference between groups. No improvements were observed for the other variables of interest in both groups.",
            "output": [
                "Does resistance training contribute to improving the metabolic profile after a 6-month weight loss program in overweight and obese postmenopausal women?"
            ]
        },
        {
            "id": "task847-a944a10adf8340e7b6308dcfd058225c",
            "input": "We developed a lactoferrin conjugate by modifying bovine lactoferrin (bLF) with a 40-kDa branched poly(ethylene glycol) (PEG) molecule (designated 40 k-PEG-bLf), and we evaluated its in vitro activities and pharmacokinetic properties.', 'We prepared 40k-PEG-bLf by amino conjugation with N-hydroxysuccinimide-activated PEG. This conjugate was purified by cation exchange chromatography and its in vitro biological activities, such as iron binding, anti-inflammatory effects, and resistance to proteolytic enzymes were investigated. In vivo pharmacokinetics analyses, were also performed to examine the rate of clearance from the plasma in rats.', 'The 40k-PEG-bLf conjugate was fully active in iron binding and exhibited 97.1 +/- 5.5% (mean +/- S.E., n = 6) of the original anti-inflammatory activity. The in vitro peptic susceptibility of 40 k-PEG-bLf revealed that the proteolytic half-life increased at least 6-fold that of unmodified LF. This PEGylated conjugate demonstrated a plasma half-life that was 8.7-fold longer than that of the unmodified bLF in rats.",
            "output": [
                "Does lactoferrin conjugated with 40-kDa branched poly ( ethylene glycol ) have an improved circulating half-life?"
            ]
        },
        {
            "id": "task847-0618fde4b69444eaa6dd7803336127d1",
            "input": "To risk-stratify patients for urinary retention after prostate brachytherapy according to a novel seed implant retention score (SIRS).', 'A total of 835 patients underwent transperineal prostate seed implant from March 1993 to January 2007; 197 patients had (125)I and 638 patients had (103)Pd brachytherapy. Four hundred ninety-four patients had supplemental external-beam radiation. The final downsized prostate volume was used for the 424 patients who had neoadjuvant hormone therapy. Retention was defined as reinsertion of a Foley catheter after the implant.', 'Retention developed in 7.4% of patients, with an average duration of 6.7 weeks. On univariate analysis, implant without supplemental external-beam radiation (10% vs. 5.6%; p = 0.02), neoadjuvant hormone therapy (9.4% vs. 5.4%; p = 0.02), baseline alpha-blocker use (12.5% vs. 6.3%; p = 0.008), and increased prostate volume (13.4% vs. 6.9% vs. 2.9%, >45 cm(3), 25-45 cm(3), <25 cm(3); p = 0.0008) were significantly correlated with increased rates of retention. On multivariate analysis, implant without supplemental external-beam radiation, neoadjuvant hormone therapy, baseline alpha-blocker use, and increased prostate volume were correlated with retention. A novel SIRS was modeled as the combined score of these factors, ranging from 0 to 5. There was a significant correlation between the SIRS and retention (p < 0.0001). The rates of retention were 0, 4%, 5.6%, 9%, 20.9%, and 36.4% for SIRS of 0 to 5, respectively.",
            "output": [
                "Do seed implant retention score predicts the risk of prolonged urinary retention after prostate brachytherapy?"
            ]
        },
        {
            "id": "task847-7285d70e1a404dc790823473e5543acd",
            "input": "Pulmonary hypertension (PH) is associated with a poor prognosis in diffuse lung disease (DLD). A study was undertaken to compare the prognostic significance of invasive and non-invasive parameters in patients with DLD and suspected PH.', 'Hospital records of consecutive patients with DLD undergoing right heart catheterisation (RHC) were reviewed (n = 66). Mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and non-invasive variables were examined against early (within 12 months) and overall mortality. A priori thresholds were examined against early mortality. Relationships between mPAP, PVR and non-invasive markers were assessed.', 'Fifty patients had PH on RHC (mean (SD) mPAP 33.5 (11.8) mm Hg, PVR 5.9 (4.3) Wood units (WU)). Raised PVR was strongly associated with early mortality (odds ratio (OR) 1.30; 95% confidence interval (CI) 1.11 to 1.52; p = 0.001), with PVR > or = 6.23 WU being the optimal threshold after adjustment for age, gender, composite physiological index (CPI) and diagnosis of idiopathic pulmonary fibrosis (OR 11.09; 95% CI 2.54 to 48.36; p = 0.001). Early mortality was linked, albeit less strongly, to right ventricular dilation at echocardiography, but not to other non-invasive variables or mPAP. Overall mortality was most strongly associated with increasing CPI levels. Correlations between PVR and non-invasive variables were moderate (R(2) <0.32), improving little following construction of a multivariate index which did not itself predict mortality.",
            "output": [
                "Does pulmonary vascular resistance predict early mortality in patients with diffuse fibrotic lung disease and suspected pulmonary hypertension?"
            ]
        },
        {
            "id": "task847-b785001fa4484088913b16d8ca040d7a",
            "input": "We investigated the association of KLOTHO gene single nucleotide polymorphisms (SNPs) with various laboratory data in 476 Japanese healthy subjects.', 'The genotyping of G-395A in the promoter region and C1818T in exon 4 was performed using PCR with confronting 2-pair primers assay.', 'Multivariate analysis adjusted for age demonstrated that in men, body-fat ratio was high, and HDL cholesterol level was low in A allele carriers of G-395A compared with GG. In women, glucose was high in A allele carriers of G-395A compared with GG, and also in T allele carriers of C1818T compared with CC. When divided into 2 groups according to age, in men <60 y, body mass index, body-fat ratio and waist circumference were high in A carriers of G-395A compared with GG. In women <60 y, bone mineral density was high in A allele carriers of G-395A compared with GG, and systolic blood pressure and glucose were high in T carriers of C1818T compared with CC.",
            "output": [
                "Are kLOTHO gene polymorphisms G-395A and C1818T associated with lipid and glucose metabolism , bone mineral density and systolic blood pressure in Japanese healthy subjects?"
            ]
        },
        {
            "id": "task847-5b340f0e6613439cbea701766431223d",
            "input": "Although cadmium (Cd) is an important and common environmental pollutant and has been linked to cardiovascular diseases, little is known about its effects in initial stages of atherosclerosis.', 'In the 195 young healthy women of the Atherosclerosis Risk Factors in Female Youngsters (ARFY) study, cadmium (Cd) level was independently associated with early atherosclerotic vessel wall thickening (intima-media thickness exceeding the 90th percentile of the distribution; multivariable OR 1.6[1.1.-2.3], P=0.016). In line, Cd-fed ApoE knockout mice yielded a significantly increased aortic plaque surface compared to controls (9.5 versus 26.0 mm(2), P<0.004). In vitro results indicate that physiological doses of Cd increase vascular endothelial permeability up to 6-fold by (1) inhibition of endothelial cell proliferation, and (2) induction of a caspase-independent but Bcl-xL-inhibitable form of cell death more than 72 hours after Cd addition. Both phenomena are preceded by Cd-induced DNA strand breaks and a cellular DNA damage response. Zinc showed a potent protective effect against deleterious effects of Cd both in the in vitro and human studies.",
            "output": [
                "Is cadmium a novel and independent risk factor for early atherosclerosis mechanisms and in vivo relevance?"
            ]
        },
        {
            "id": "task847-82c7721e7e6143f7bf10df14d5796c72",
            "input": "Current clinical tools to identify lacunar infarct patients at risk of deterioration are inadequate, and imaging techniques to predict fluctuation and deterioration would be of value. We sought to determine the occurrence of MRI perfusion-weighted imaging (PWI) abnormalities in lacunes, and whether they help predict clinical and radiological outcome.', 'Patients with lacunar stroke or TIA were selected from a prospective MR imaging study. MRI was performed within 24 h of the event and follow-up imaging completed at 30 or 90 days. Baseline perfusion maps were qualitatively assessed and infarct volumes measured. Early clinical deterioration (NIHSS worsening of > or = 3 points within 72 h of event) and 90-day modified Rankin Scale score (mRS) were recorded.', 'Twenty-two patients were included. Fifteen (68.2%) had abnormal PWI at the site of the diffusion-weighted imaging lesion. Patients with abnormal PWI were more likely to have stroke than TIA as their index event (RR 2.2, 95% CI 0.9-5.2, p = 0.02). Early clinical deterioration occurred in 4 patients (18.2%), all of whom had abnormal PWI. PWI lesions were not associated with a higher 90-day NIHSS or mRS score, nor did they predict infarct volume growth.",
            "output": [
                "Does normal magnetic resonance perfusion-weighted imaging in lacunar infarcts predict a low risk of early deterioration?"
            ]
        },
        {
            "id": "task847-9dffd900d0a1487aabca8b26a2671d74",
            "input": "Neuropeptides (NPs) may play an important role in the pathogenesis of atopic dermatitis (AD) by regulating immune responses and contributing to the cross-talk between the immune and nervous systems.', 'To assess the ability of NPs to influence interleukin (IL)-13 and interferon (IFN)-gamma production and the expression of the activation marker HLA-DR in skin memory T cells [cutaneous lymphocyte-associated antigen (CLA)+ T cells] from patients with AD with severe, chronic lesions and intense pruritus, and from nonatopic controls.', 'Cells were cultured in the presence and absence of different NPs, calcitonin gene-related peptide (CGRP), somatostatin (SOM) and substance P (SP). IL-13 and IFN-gamma production and HLA-DR expression were measured in both CLA+ and CLA- T-cell subsets by flow cytometry.', 'CGRP increased IL-13 production in peripheral blood mononuclear cells from patients with AD (P < 0.05), with no changes detected in the presence of SOM or SP. These patients with AD had a lower expression of CGRP receptor compared with controls (P < 0.05). Memory T cells incubated with CGRP also showed an increase in IL-13 (P < 0.05) and HLA-DR (P < 0.05) in CLA+ T cells from patients with AD compared with controls, but not in CLA- T cells. Patients with a higher production of IL-13 were those with higher total IgE and percentage of skin area involved. Furthermore, the IL-13/IFN-gamma ratio was increased in patients with AD after cells were cultured with CGRP (P < 0.05).",
            "output": [
                "Does calcitonin gene-related peptide modulate interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis?"
            ]
        },
        {
            "id": "task847-8c5211aa87a049d08dee9046437314f8",
            "input": "We aimed at analyzing the frequency, clinical characteristics, and trends associated with the occurrence of diabetic ketoacidosis (DKA) at the onset of type 1 diabetes on the basis of long-term follow-up data.', 'A total of 106 pediatric diabetes centers in Germany and Austria participated in this study. Data from 14,664 patients with type 1 diabetes collected between 1995 and 2007 were suitable for evaluation. DKA was defined and classified according to the International Society for Pediatric and Adolescent Diabetes consensus guidelines.', 'DKA was observed in 21.1% of patients. The frequency of DKA, including the severe form, remained unchanged throughout the 13-year observation period. The frequency of DKA was particularly striking among children <5 years of age (26.5%).",
            "output": [
                "Is ketoacidosis at diabetes onset still frequent in children and adolescents : a multicenter analysis of 14,664 patients from 106 institutions?"
            ]
        },
        {
            "id": "task847-6cbd0a111e634b9f9fe73cfe74c7e5a6",
            "input": "While tumor infiltrating lymphocytes (TIL) have been shown to independently predict survival in primary colorectal cancer, the prognostic implications of TIL in resectable colorectal cancer liver metastases (CRCLM) have not been previously defined. This study examines the correlation between TIL numbers and survival following hepatic resection.', 'We studied patients who survived <or=2 or >or=10 years following CRCLM resection. Immunohistochemistry was performed on tissue microarrays (TMAs) to determine the number of T cells within CRCLM. Correlation between TIL frequency and <or=2 or >or=10 year survival was determined while controlling for established prognostic factors.', 'Of 162 patients, 104 survived <or=2 years and 58 survived >or=10 years. Independent correlates of 10-year survival following CRCLM resection included a high number of CD8 T cells, a low number of CD4 T cells, and a clinical risk score of <or=2 (P < 0.001). Among 10-year survivors, 31% of patients had a high number of CD8 T cells compared with 8% for <or=2 year survivors (P < 0.01). Surprisingly, only 22% of 10-year survivors had a high number of CD4 T cells, in contrast to 69% of those who died within 2 years (P < 0.001). The combination of CD8 and CD4 T cell counts was a more powerful predictor of survival than either marker alone.",
            "output": [
                "Does t cell infiltrate predict long-term survival following resection of colorectal cancer liver metastases?"
            ]
        },
        {
            "id": "task847-4604589105a943a887b1cc369d47d787",
            "input": "B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection.', 'N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations.', \"A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters.",
            "output": [
                "Does the change in B-type natriuretic peptide levels over time predict significant rejection in cardiac transplant recipients?"
            ]
        },
        {
            "id": "task847-e3c09b683405490caf26478d4358eaa5",
            "input": "Overweight/obesity is known to increase the risk of developing renal cell carcinoma (RCC). However, data on the prognostic impact of overweight in RCC is still conflicting. We assessed whether different body mass index (BMI) levels at the time of surgery had an effect on the long-term prognosis of RCC patients.', \"We evaluated 771 patients, with complete information about their BMI, who had undergone renal surgery for RCC between 1990 and 2005 at the authors' institution; the mean follow-up was 5.48 years.\", 'Underweight, normal weight, pre-obesity, and obesity were diagnosed in 4 (0.5%), 239 (31%), 356 (46.2%), and 172 (22.3%) RCC patients, respectively. Overweight (BMI >25) was significantly associated with younger age (P = 0.004) and positive nodal status (P = 0.04) but not with tumor stage, grade, visceral metastasis, gender, histological subtype, or tumor-related symptoms. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 80% as opposed to 72% for patients with a BMI below 25 (P = 0.003). Interestingly, subgroup analysis revealed that the positive association between overweight and survival was even more pronounced in organ-confined (P < 0.001) RCC, but no correlation was observed in advanced disease (P = 0.23).",
            "output": [
                "Is overweight associated with improved cancer-specific survival in patients with organ-confined renal cell carcinoma?"
            ]
        },
        {
            "id": "task847-45efe205bb2f47b18f1708a8093faa54",
            "input": "During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles (AuNPs), which differed in size and purification grade (presence or absence of sodium citrate residues on the particle surface) in vitro, in the human alveolar type-II (ATII)-like cell lines A549 and NCIH441.', 'We found that the presence of sodium citrate residues on AuNPs impaired the viability of the ATII-like cell lines A549 and NCIH441. Interestingly, the presence of an excess of sodium citrate on the surface of NPs not only reduced the in vitro viability of the cell lines A549 and NCIH441, as shown by MTT assay, but also affected cellular proliferation and increased the release of lactate dehydrogenase (LDH), as demonstrated by Ki-67 and LDH-release assays respectively. Furthermore, we investigated the internalization of AuNPs by transmission electron microscopy (TEM) and we observed that particles were internalized by active endocytosis in the cell lines A549 and NCIH441 within 3 hr. In addition, gold particles accumulated in membrane-bound vesicles and were not found freely dispersed in the cytoplasm.",
            "output": [
                "Do gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441?"
            ]
        },
        {
            "id": "task847-9423642fca0b49e4a5a2708317574f17",
            "input": "In streptozotocin-injected rats (STZ-rats), we previously demonstrated a role for angiotensin II (AT-II) in cardiac remodelling and insulin resistance partially counteracted by in vivo treatment with losartan, an AT-II receptor antagonist.We now aimed to investigate the effect of treating diabetic STZ-rats with losartan on diabetes vascular response to vasoconstrictors.', 'Male Wistar rats were randomly divided in four groups, two of them were assigned to receive losartan in the drinking water (20 mg/kg/day) until the experiment ending (3 weeks afterward). After 1 week, two groups, one of which receiving losartan, were injected in the tail vein with citrate buffer (normoglycemic, N and normoglycemic, losartan-treated, NL). The remaining received a single injection of streptozotocin (50 mg/kg in citrate i.v.) thus becoming diabetic (D) and diabetic losartan-treated (DL). Plasma glycaemia and blood pressure were measured in all animals before the sacrifice (15 days after diabetes induction).In aortic strips isolated from N, NL, D and DL rats we evaluated i) the isometric concentration-dependent contractile response to phenylephrine (Phe) and to AT-II; ii) the RhoA-kinase (ROCK1) activity and expression by enzyme-immunoassay and Western blot respectively.', 'The concentration-dependent contractile effect of Phe was similar in aortas from all groups, whereas at all concentrations tested, AT-II contraction efficacy was 2 and half and 1 and half times higher in D and DL respectively in comparison with N and NL. AT-II contracture was similarly reduced in all groups by AT-II receptor antagonists, irbesartan or irbesartan plus PD123319. HA-1077 (10 microM), an inhibitor of ROCK1 activity, reduced AT-II efficacy (Deltamg/mg tissue w.w.) by -3.5 +/- 1.0, -4.6 +/- 1.9, -22.1 +/- 2.2 and -11.4 +/- 1.3 in N, NL, D and DL respectively). ROCK1 activity and expression were higher in D than in N/NL and DL aortas.",
            "output": [
                "Does losartan counteract the hyper-reactivity to angiotensin II and ROCK1 over-activation in aortas isolated from streptozotocin-injected diabetic rats?"
            ]
        },
        {
            "id": "task847-20ed6132251240e3b38f82946c35042a",
            "input": "In vivo proton magnetic resonance spectroscopy (1H-MRS) studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection.', 'Changes in the N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), creatine (Cr) and glutamine/glutamate (Glx) resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi). At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions.",
            "output": [
                "Does in vivo proton magnetic resonance spectroscopy reveal region specific metabolic responses to SIV infection in the macaque brain?"
            ]
        },
        {
            "id": "task847-83040a4e38544b64ab5a91674348d1a0",
            "input": "Hydrogen sulfide (H2S) is a well-known cytotoxic gas. Recently it has been shown to protect neurons against oxidative stress caused by glutamate, hypochlorous acid (HOCl), and beta-amyloid. The aim of the present study is to explore the cytoprotection of H2S against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced apoptosis and the molecular mechanisms underlying in PC12 cells, a rat cell line derived from pheochromocytoma cells.', 'Cell viability was determined by the conventional 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. Apoptosis was assessed by Hoechst 33258 nuclear staining and flow cytometric (FCM) analysis after propidium iodide staining. The mitochondrial membrane potential (MMP) was measured by rhodamine 123 (Rh123) probe and reactive oxygen species (ROS) were measured by dihydrorhodamine probe using FCM analysis.', 'MPP(+) reduced the cell viability and induced apoptosis of PC12 cells along with dissipation of MMP as well as overproduction of ROS. Sodium hydrosulfide (NaHS), a H2S donor, protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by reducing the loss of MMP, but also by attenuating an increase in intracellular ROS.",
            "output": [
                "Does hydrogen sulfide inhibit MPP ( + ) -induced apoptosis in PC12 cells?"
            ]
        },
        {
            "id": "task847-8f3a2f30be3e4a8c817bf03780546147",
            "input": "The viral genome of hepatitis C virus constitutes a 9.6-kb single-stranded positive-sense RNA which encodes altogether 11 viral proteins. In order to study the humoral immune responses against different HCV proteins in patients suffering from chronic HCV infection, we produced three structural (core, E1 and E2) and six nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B) in Sf9 insect cells by using the baculovirus expression system.', 'The recombinant HCV core, E1, E2, NS2, NS3, NS4A, NS4B, NS5A and NS5B proteins were purified and used in Western blot analysis to determine antibody responses against individual HCV protein in 68 HCV RNA and antibody positive human sera that were obtained from patients suffering from genotype 1, 2, 3 or 4 infection. These sera were also analysed with INNO-LIA Score test for HCV antibodies against core, NS3, NS4AB and NS5A, and the results were similar to the ones obtained by Western blot method. Based on our Western blot analyses we found that the major immunogenic HCV antigens were the core, NS4B, NS3 and NS5A proteins which were recognized in 97%, 86%, 68% and 53% of patient sera, respectively. There were no major genotype specific differences in antibody responses to individual HCV proteins. A common feature within the studied sera was that all except two sera recognized the core protein in high titers, whereas none of the sera recognized NS2 protein and only three sera (from genotype 3) recognised NS5B.",
            "output": [
                "Are hepatitis C virus core , NS3 , NS4B and NS5A the major immunogenic proteins in humoral immunity in chronic HCV infection?"
            ]
        },
        {
            "id": "task847-2c0b1efe8ee546979ff7e919a55004d6",
            "input": "High-fat diets promote hepatic lipid accumulation. Paradoxically, these diets also induce lipogenic gene expression in rodent liver. Whether high expression of these genes actually results in an increased flux through the de novo lipogenic pathway in vivo has not been demonstrated.', 'To interrogate this apparent paradox, we have quantified de novo lipogenesis in C57Bl/6J mice fed either chow, a high-fat or a n-3 polyunsaturated fatty acid (PUFA)-enriched high-fat diet. A novel approach based on mass isotopomer distribution analysis (MIDA) following 1-(13)C acetate infusion was applied to simultaneously determine de novo lipogenesis, fatty acid elongation as well as cholesterol synthesis. Furthermore, we measured very low density lipoprotein-triglyceride (VLDL-TG) production rates. High-fat feeding promoted hepatic lipid accumulation and induced the expression of lipogenic and cholesterogenic genes compared to chow-fed mice: induction of gene expression was found to translate into increased oleate synthesis. Interestingly, this higher lipogenic flux (+74 microg/g/h for oleic acid) in mice fed the high-fat diet was mainly due to an increased hepatic elongation of unlabeled palmitate (+66 microg/g/h) rather than to elongation of de novo synthesized palmitate. In addition, fractional cholesterol synthesis was increased, i.e. 5.8+/-0.4% vs. 8.1+/-0.6% for control and high fat-fed animals, respectively. Hepatic VLDL-TG production was not affected by high-fat feeding. Partial replacement of saturated fat by fish oil completely reversed the lipogenic effects of high-fat feeding: hepatic lipogenic and cholesterogenic gene expression levels as well as fatty acid and cholesterol synthesis rates were normalized.",
            "output": [
                "Does high fat feeding induce hepatic fatty acid elongation in mice?"
            ]
        },
        {
            "id": "task847-6c9db657869349448dae65001f45ced5",
            "input": "In cystic fibrosis (CF), lung disease is the predominant cause of morbidity and mortality. Little is known about the spectrum of structural abnormalities on CT scans from patients with CF with severe advanced lung disease (SALD). No specific CT scoring system for SALD is available.', 'To design a quantitative CT scoring system for SALD, to determine the spectrum of structural abnormalities in patients with SALD and to correlate the SALD system with an existing scoring system for mild CF lung disease and pulmonary function tests (PFTs).', '57 patients with CF contributed one CT made during screening for lung transplantation. For the SALD system, lung tissue was divided into four components: infection/inflammation (including bronchiectasis, airway wall thickening, mucus and consolidations), air trapping/hypoperfusion, bulla/cysts and normal/hyperperfused tissue. The volume proportion of the components was estimated on a 0-100% scale; mean volumes for the whole lung were computed. Scores were correlated with Brody-II scores and PFTs.', 'The SALD system identified a wide spectrum of structural abnormalities ranging from predominantly infection/inflammation to predominantly air trapping/hypoperfusion. SALD infection/inflammation scores correlated with Brody-II scores (r(s) = 0.36-0.64) and SALD normal/hyperperfusion scores correlated with forced expiratory volume in 1 s (FEV(1); r(s) = 0.37). Reproducibility for both systems was good.",
            "output": [
                "Does the spectrum of structural abnormalities on CT scan from patients with CF with severe advanced lung disease?"
            ]
        },
        {
            "id": "task847-af321bb38d3c4b9fa1947fa120674104",
            "input": "Violence and safety exposures, primarily in the form of intimate partner violence (IPV) exposures, have been associated with increased healthcare utilization in women and variable associations with preventive services. It remains unknown, however, if broader measures of violence and safety exposures are associated with preventive healthcare utilization.', 'Data from the 2004 The Philadelphia Health Management Corporation survey were used to compare self-reported utilization of preventive healthcare services for participants who did and did not report exposures to violence or have safety concerns during the past year, using novel but nonvalidated measures of violence and safety concerns. The sample included women aged 18-96 years who reported having a usual source of care. Measures of preventive healthcare utilization included timing of last mammogram, cervical cytology, breast examination, blood cholesterol testing, blood pressure measurement, and screening for colon cancer.', 'The survey had an American Association for Public Opinion Research response rate of 30.4%. Of the 6285 women surveyed who reported having a usual source of care, 456 (7.3%) reported either an exposure to violence or safety concerns, and 5821 did not. Using logistic regression models, women aged 18-65 years who reported safety concerns were less likely to report having cervical cancer testing in the past 12 months (OR 0.68, 95% CI 0.49-0.94). Women > or =40 years who reported safety concerns in the last year were less likely to report having clinical breast examinations (OR 0.63, 95% CI 0.43-0.93) or mammography (OR 0.57, 95% CI 0.39-0.83). Physical violence exposure was not significantly associated with preventive healthcare utilization.",
            "output": [
                "Do women with safety concerns report fewer gender-specific preventive healthcare services?"
            ]
        },
        {
            "id": "task847-4b4be1ffd96a44c586fccfd3b7396bb8",
            "input": "Diarrhea is the third leading infectious cause of death worldwide and is estimated to be responsible for approximately 2 million deaths a year. While many infectious causes of diarrhea have been established, approximately 40% of all diarrhea cases are of unknown etiology. In an effort to identify novel viruses that may be causal agents of diarrhea, we used high throughput mass sequencing to analyze stool samples collected from patients with acute diarrhea.', \"Sequences with limited similarity to known picornaviruses were detected in a stool sample collected in Australia from a child with acute diarrhea. Using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, a 6383 bp fragment of the viral genome was sequenced. Phylogenetic analysis demonstrated that this virus was highly divergent from, but most closely related to, members of the genus Kobuvirus. We have tentatively named this novel virus klassevirus 1. We also detected klassevirus 1 by RT-PCR in a diarrhea specimen collected from a patient in St. Louis, United States as well as in untreated sewage collected in Barcelona, Spain.",
            "output": [
                "Is klassevirus 1 , a previously undescribed member of the family Picornaviridae , globally widespread?"
            ]
        },
        {
            "id": "task847-26df128afe1f48e6a643c80e002c239e",
            "input": "Surfactant protein A (SP-A) is a C-type lectin involved in surfactant homeostasis as well as host defense in the lung. We have recently demonstrated that SP-A enhances the killing of bacillus Calmette-Guerin (BCG) by rat macrophages through a nitric oxide-dependent pathway. In the current study we have investigated the role of tyrosine kinases and the downstream mitogen-activated protein kinase (MAPK) family, and the transcription factor NFkappaB in mediating the enhanced signaling in response to BCG in the presence of SP-A.', 'Human SP-A was prepared from alveolar proteinosis fluid, and primary macrophages were obtained by maturation of cells from whole rat bone marrow. BCG-SP-A complexes were routinely prepared by incubation of a ratio of 20 microg of SP-A to 5 x 105 BCG for 30 min at 37 degrees C. Cells were incubated with PBS, SP-A, BCG, or SP-A-BCG complexes for the times indicated. BCG killing was assessed using a 3H-uracil incorporation assay. Phosphorylated protein levels, enzyme assays, and secreted mediator assays were conducted using standard immunoblot and biochemical methods as outlined.', 'Involvement of tyrosine kinases was demonstrated by herbimycin A-mediated inhibition of the SP-A-enhanced nitric oxide production and BCG killing. Following infection of macrophages with BCG, the MAPK family members ERK1 and ERK2 were activated as evidence by increased tyrosine phosphorylation and enzymatic activity, and this activation was enhanced when the BCG were opsonized with SP-A. An inhibitor of upstream kinases required for ERK activation inhibited BCG- and SP-A-BCG-enhanced production of nitric oxide by approximately 35%. Macrophages isolated from transgenic mice expressing a NFkappaB-responsive luciferase gene showed increased luciferase activity following infection with BCG, and this activity was enhanced two-fold in the presence of SP-A. Finally, lactacystin, an inhibitor of IkappaB degradation, reduced BCG- and SP-A-BCG-induced nitric oxide production by 60% and 80% respectively.",
            "output": [
                "Are mitogen-activated protein kinases and NFkappaB involved in SP-A-enhanced responses of macrophages to mycobacteria?"
            ]
        },
        {
            "id": "task847-813da74cc391418cbe5e1a8f83bd6781",
            "input": "The yeast cell cycle is largely controlled by the cyclin-dependent kinase (CDK) Cdc28. Recent evidence suggests that both CDK complex stability as well as function during mitosis is determined by precise regulation of Swe1, a CDK inhibitory kinase and cyclin binding partner. A model of mitotic progression has been provided by study of filamentous yeast. When facing nutrient-limited conditions, Ras2-mediated PKA and MAPK signaling cascades induce a switch from round to filamentous morphology resulting in delayed mitotic progression.', 'To delineate how the dimorphic switch contributes to cell cycle regulation, temperature sensitive cdc28 mutants exhibiting constitutive filamentation were subjected to epistasis analyses with RAS2 signaling effectors. It was found that Swe1-mediated inhibitory tyrosine phosphorylation of Cdc28 during filamentous growth is in part mediated by Ras2 activation of PKA, but not Kss1-MAPK, signaling. This pathway is further influenced by Cks1, a conserved CDK-binding partner of elusive function with multiple proposed roles in CDK activation, transcriptional regulation and ubiquitin-mediated proteasome degradation.",
            "output": [
                "Do morphogenesis signaling components influence cell cycle regulation by cyclin dependent kinase?"
            ]
        },
        {
            "id": "task847-c85e889489464c5fb6f11c00af850b29",
            "input": "Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia.\", 'RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin.",
            "output": [
                "Do calyx and dimorphic neurons of mouse Scarpa 's ganglion express histamine H3 receptors?"
            ]
        },
        {
            "id": "task847-e168dff805ec43e59411f3b25befee8b",
            "input": "Primary pneumonic plague is a rare but often fatal form of Yersinia pestis infection that results from direct inhalation of bacteria and is potentially transmissible from person to person. We describe a case of primary pneumonic plague in a wildlife biologist who was found deceased in his residence 1 week after conducting a necropsy on a mountain lion.', \"To determine cause of death, a postmortem examination was conducted, and friends and colleagues were interviewed. Physical evidence was reviewed, including specimens from the mountain lion and the biologist's medical chart, camera, and computer. Human and animal tissues were submitted for testing. Persons in close contact (within 2 meters) to the biologist after he had developed symptoms were identified and offered chemoprophylaxis.\", 'The biologist conducted the necropsy in his garage without the use of personal protective equipment. Three days later, he developed fever and hemoptysis and died approximately 6 days after exposure. Gross examination showed consolidation and hemorrhagic fluid in the lungs; no buboes were noted. Plague was diagnosed presumptively by polymerase chain reaction and confirmed by culture. Tissues from the mountain lion tested positive for Y. pestis, and isolates from the biologist and mountain lion were indistinguishable by pulsed-field gel electrophoresis. Among 49 contacts who received chemoprophylaxis, none developed symptoms consistent with plague.",
            "output": [
                "Do primary pneumonic plague contracted from a mountain lion carcass?"
            ]
        },
        {
            "id": "task847-25b00af3713d462da00bf48c3c290c9e",
            "input": "Human plasma factor XI is a homodimer, with each monomer comprising a catalytic domain and four homologous 'apple' domains. The monomers bind to each other through non-covalent bonds and through a disulfide bond between Cys321 residues in apple 4 domains.\", 'To identify residues essential for dimerization in the FXI monomer interface.', 'Specificity-determining residues in apple 4 domains were sought by sequence alignment of FXI and prekallikrein apple domains in different species. Specific residues identified in apple 4 domains were mutagenized and expressed in baby hamster kidney (BHK) cells for evaluation of their effect on FXI dimerization, analyzed by non-reduced sodium dodecylsulfate polyacrylamide gel electrophoresis and size-exclusion chromatography.', 'Among the 19 residues of the FXI monomer interface, Leu284, Ile290 and Tyr329 were defined as specificity-determining residues. Substitutions of these residues or pairs of residues did not affect FXI synthesis and secretion from transfected BHK cells, but did impair dimerization, despite the presence of cysteine at position 321. The double mutant 284A/290A yielded predominantly a monomer, whereas all other single or double mutants yielded monomers as well as disulfide-bonded dimers.",
            "output": [
                "Do three residues at the interface of factor XI ( FXI ) monomers augment covalent dimerization of FXI?"
            ]
        },
        {
            "id": "task847-7af9d8ef04954be3ae0baf4b14ab8ed8",
            "input": "To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP-4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration.', 'Using RNase protection assays and enzyme-linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/MCP-1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression.', 'The interleukin-6 (IL-6)-type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL-6 nor tumor necrosis factor alpha could stimulate the expression of CCL13 in synovial fibroblasts; IL-1beta was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT-5, ERK-1/2, and p38 as critical factors involved in OSM-dependent transcription and messenger RNA stabilization of CCL13.",
            "output": [
                "Does induction of CCL13 expression in synovial fibroblasts highlight a significant role of oncostatin M in rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-af8e36d3ccfe4bae8c8112466d3d73aa",
            "input": "Myeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture. The presence of these cells in precursor lesions to acute rupture (thin cap atheroma, or vulnerable plaque) and within thrombi adjacent to ruptures has not been described, nor an association with iron-containing macrophages within unstable plaques.', \"We studied 61 acute ruptures, 15 organizing ruptures, 31 thin cap fibroatheromas, and 28 fibroatheromas from 72 sudden coronary death victims by immunohistochemical and histochemical techniques. Inflammatory cells were typed with anti-CD68 (macrophages), anti-BP-30 (neutrophil bactericidal glycoprotein), and anti-MPO. Iron was localized by Mallory's Prussian blue stain. In selected plaques alpha smooth muscle actin (DAKO, Carpinteria, CA, clone M0851) was performed.\", 'MPO positive cells were present in 79% of ruptured caps, 28% of thin cap fibroatheroma, and no fibroatheromas; neutrophils were present in 72% of ruptures, 8% of thin cap fibroatheromas, and no fibroatheromas. Iron containing foam cells were present in the caps of 93% of acute ruptures, of 85% of organizing ruptures, 20% of thin cap atheromas, and 10% of fibroatheromas. MPO positive cells were more frequent in occlusive than non-occlusive thrombi adjacent to ruptures (p = .006) and were more numerous in diabetics compared to non-diabetics (p = .002)",
            "output": [
                "Do monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques?"
            ]
        },
        {
            "id": "task847-ce350bb57e6846df88d502c05a62b62a",
            "input": "Centrosome orientation toward the leading edge of migrating cells depends on dynein and microtubules (MTs), as well as a number of signaling factors at the leading edge. However, centrosomes are maintained at the cell center during orientation in fibroblasts, suggesting that factors working at sites other than the leading edge may also be involved.', 'In a search for factors that function with dynein in centrosome orientation, we found that the polarity protein Par3 associated with dynein and that knockdown of Par3 inhibited centrosome orientation by disrupting the position of the centrosome at the cell center; this disrupted centrosome positioning is the same phenotype as that observed with dynein inhibition. Par3 associated with dynein through its N-terminal dimerization and PDZ1 domains and interacted specifically with dynein light intermediate chain 2 (LIC2). siRNA knockdown of LIC2, but not LIC1, or overexpression of LIC2 or the N-terminal domain of Par3, also inhibited centrosome orientation by disrupting centrosome position. In wound-edge fibroblasts, Par3 specifically localized to cell-cell contacts where it overlapped with MT ends and dynein puncta in a LIC2-dependent fashion. Live imaging showed that MTs exhibited increased pausing at cell-cell contacts compared to the leading edge and that this elevated pausing was dependent on Par3 and LIC2.",
            "output": [
                "Do par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration?"
            ]
        },
        {
            "id": "task847-06e43837b06a435fa68e3134524ff3bf",
            "input": "Few prospective studies have examined personality and depression in older adults. The authors investigated whether the Five-Factor Model of personality traits-Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness-and trait combinations (styles) are related to incident major or minor depression.', 'Prospective data were gathered on a community sample of 512 older adults with disability and a history of significant health care utilization who were enrolled in a Medicare Demonstration Project.', 'Depression and personality traits and styles were assessed at baseline; depression was assessed again at approximately 12 and 22 months.', 'Participants who developed incident major depression were compared with those free of depression at all three assessments. Similar analyses were done for minor depression.', 'High Neuroticism and low Conscientiousness were risk factors for both major and minor depression. Combinations of high Neuroticism with low or high Extraversion or high Openness conferred risk for major depression. Other novel findings for major depression revealed new trait combinations of low Conscientiousness with low or high Extraversion, high Openness, or low Agreeableness. Three trait combinations, all involving low Conscientiousness, predicted risk for minor depression: high Neuroticism, high Agreeableness, and low Openness.",
            "output": [
                "Are the personality domains and styles of the five-factor model related to incident depression in Medicare recipients aged 65 to 100?"
            ]
        },
        {
            "id": "task847-13570c44a9ef4c469f77abe5c889bf27",
            "input": "The measurement of affective symptoms in older persons who decline cognitively is uncertain. The authors investigated whether mood variability predicts dementia in patients with age-related macular degeneration (AMD).', 'Three-year observational study after a clinical trial.', 'Community follow-up of outpatients ascertained from retina clinics.', 'One hundred sixty patients with AMD.', \"Geriatric Depression Scale (GDS) administered every 2 weeks for 6 months to subjects; Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) administered to subjects' knowledgeable informants.\", 'Twenty-three subjects (14.4%) declined cognitively. Age, education, baseline GDS score > or =5, and variability in GDS scores (i.e., fluctuations between adjacent time points) were associated with cognitive decline. For GDS variability, each 1 unit increase in the residual standard deviation (SD) of the GDS increased the risk for cognitive decline by 93% (IDR = 1.92; 95% CI [1.27-2.91]). Thus, subjects with a residual SD of 1 were nearly twice as likely to become demented as subjects with no variability in GDS scores. The risk for subjects with SDs of 2 increased more than threefold (IDR = 3.68; 95% CI [1.61-8.47]). A multiple regression analysis showed that GDS variability was a significant risk factor for dementia after controlling for significant covariates.",
            "output": [
                "Does variability in depressive symptoms predict cognitive decline in age-related macular degeneration?"
            ]
        },
        {
            "id": "task847-1912acbb94f340799202dfcaec17c738",
            "input": "Determining the ways in which personality traits interact with contextual determinants to shape social behavior remains an important area of empirical investigation. The specific personality trait of neuroticism has been related to characteristic negative emotionality and associated with heightened attention to negative, emotionally arousing environmental signals. However, the mechanisms by which this personality trait may shape social behavior remain largely unspecified.', 'We employed eye tracking to investigate the relationship between characteristics of visual scanpaths in response to emotional facial expressions and individual differences in personality. We discovered that the amount of time spent looking at the eyes of fearful faces was positively related to neuroticism.",
            "output": [
                "Do individual differences in personality predict how people look at faces?"
            ]
        },
        {
            "id": "task847-c3655962ba4b49d0865c705fd5e13746",
            "input": "Triterpene alcohols and acids are multifunctional compounds widely distributed throughout the plant kingdom that exhibit a variety of beneficial health properties, being synthetic analogs of oleanolic acid under clinical evaluation as anti-tumoral therapeutic agents. However, the antineoplastic activity of two natural occurring triterpenoid alcohols extracted from olive oil, erythrodiol (an intermediate from oleanolic acid), and its isomer, uvaol, has barely been reported, particularly on brain cancer cells. Astrocytomas are among the most common and aggressive type of primary malignant tumors in the neurological system lacking effective treatments, and in this study, we addressed the effect of these two triterpenic diols on the human 1321N1 astrocytoma cell line.', 'Erythrodiol and uvaol effectively affected cell proliferation, as well as cell cycle phases and induced 1321N1 cell death. Both triterpenes successfully modulated the apoptotic response, promoting nuclear condensation and fragmentation. They caused retraction and rounding of cultured cells, which lost adherence from their supports, while F-actin and vimentin filaments disappeared as an organized cytoplasmic network. At molecular level, changes in the expression of surface proteins associated with adhesion or death processes were also observed. Moreover, triterpene exposure resulted in the production of reactive oxygen species (ROS) with loss of mitochondrial transmembrane potential, and correlated with the activation of c-Jun N-terminal kinases (JNK). The presence of catalase reversed the triterpenic diols-induced mitochondrial depolarization, JNK activation, and apoptotic death, indicating the critical role of ROS in the action of these compounds.",
            "output": [
                "Do natural triterpenic diols promote apoptosis in astrocytoma cells through ROS-mediated mitochondrial depolarization and JNK activation?"
            ]
        },
        {
            "id": "task847-1509ca412a8040c5b97516430f016f40",
            "input": "To compare single- and multiple-dose maraviroc exposures in cervicovaginal fluid (CVF) and vaginal tissue (VT) with blood plasma (BP) and quantify maraviroc protein binding in CVF.', 'Open-label pharmacokinetic study.', 'In 12 HIV-negative women, 7 paired CVF and BP samples were collected over 12 hours after 1 maraviroc dose. Subjects then received maraviroc twice daily for 7 days. After the last dose, subjects underwent CVF and BP sampling as on day 1, with additional sampling during terminal elimination. VT biopsies were obtained at steady state.', 'Day 1 and day 7 median maraviroc CVF AUCtau were 1.9- and 2.7-fold higher, respectively, than BP. On day 1, 6 of 12 subjects had detectable maraviroc CVF concentrations within 1 hour; 12 of 12 were detectable within 2 hours, and all exceeded the protein-free IC90. On day 7, maraviroc CVF protein binding was 7.6% and the VT AUCtau was 1.9-fold higher than BP. Maraviroc CVF concentrations 72 hours after dose and BP concentrations 12 hours after dose were similar.",
            "output": [
                "Does maraviroc concentrate in the cervicovaginal fluid and vaginal tissue of HIV-negative women?"
            ]
        },
        {
            "id": "task847-27edb7174c68437ba7a91f97bdd602c2",
            "input": "To explore the effect of arsenic trioxide (As2O3) on the growth inhibition of imatinib (IM)-resistant bcr-abl mutant cell lines in vitro.', 'Cell growth of one IM-sensitive cell line, 32Dp210 and 15 IM-resistant cell lines including T315I and other 14 bcr-abl mutants were detected by MTT assay after treatment with IM and As2O3. The cell lines with 5 frequently observed mutants in CML patients were analyzed for apoptosis by flow cytometry with Annexin V and PI staining as well as the expression of bcr-abl fusion protein, phosphorylated CRKL protein and apoptosis-related proteins by Western blot.', 'The fifty percent inhibition concentration (IC50) values of As2O3 for 15 IM-resistant cell lines were 2.6-5.3 fold lower than that for IM-sensitive cell line. For the 5 bcr-abl mutants frequently happened in CML patients, As2O3 significantly inhibited the expression of bcr-abl fusion protein and phosphorylated CRKL and induced apoptosis in a dose-dependent manner as compared with that for 32Dp210. Coincidently, the cell apoptosis was induced through caspase-3, 8 and 9 pathways.",
            "output": [
                "Does [ Arsenic trioxide inhibit cell growth in imatinib-resistant bcr-abl mutant cell lines in vitro ]?"
            ]
        },
        {
            "id": "task847-09b91da7990842818072e3679300282e",
            "input": "Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by abscess formation localized to apocrine sweat gland-bearing skin. The most important factor in patients' overall assessment of disease severity is pain. The duration of abscesses takes days to weeks and are always painful.\", 'To assess the efficacy of self-treatment with topical 15% resorcinol in an open study.', 'The case notes of 12 women with stage 1 or 2 HS treated with topical resorcinol and followed up for at least 1 year were reviewed. The patients rated the efficacy of treatment on global maximum pain of nodules and abscesses on a visual analogue scale (VAS) and by self-report of the mean duration (days) of a painful lesion.', 'All patients experienced a significant decrease in pain as assessed by VAS and reported a reduction in mean duration of the painful abscesses.",
            "output": [
                "Does resorcinol peel as a possible self-treatment of painful nodules in hidradenitis suppurativa?"
            ]
        },
        {
            "id": "task847-c190796e50734d50a76eddbad99210ef",
            "input": "Extranodal natural killer/T-cell lymphoma (NKTCL) is a clinically heterogeneous disease with a poor prognosis, requiring risk-stratified management in affected patients. Recently, tumor microenvironment including regulatory T cells (Tregs) has been implicated as a prognostic marker in certain types of lymphoma.', 'We collected 64 NKTCL cases and numerically quantified the amount of tumor-infiltrating FOXP3-positive Tregs by automated slide scanning and image analysis program after immunohistochemical staining using anti-FOXP3 antibody.', 'Patients were able to be classified into two end groups by their level of Tregs. Twenty-eight (44%) patients had Tregs <50/0.40 mm(2), while 36 (56%) had Tregs > or =50/0.40 mm(2) within the tumor. The decreased number of Tregs (<50/0.40 mm(2)) was more common in patients with poor performance status or in those presented in non-upper aerodigestive tract. However, the level of Tregs was not associated with other prognostic factors, including stage, lactate dehydrogenase level, International Prognostic Index, and NKTCL Prognostic Index. Importantly, patients with increased numbers of Tregs (> or =50/0.40 mm(2)) showed prolonged overall and progression-free survival (P = 0.0005 and P = 0.0079, respectively). The number of FOXP3-positive Tregs was an independent prognostic factor (P = 0.001) by multivariate analysis.",
            "output": [
                "Is increased quantity of tumor-infiltrating FOXP3-positive regulatory T cells an independent predictor for improved clinical outcome in extranodal NK/T-cell lymphoma?"
            ]
        },
        {
            "id": "task847-ed96804ef530483693d41d0aa10a59ff",
            "input": "The Eustachian tube (ET) plays an important role in maintaining a normally aerated middle ear. Inflammation in middle ear disease is related to ET dysfunction, and postoperative restoration of middle ear integrity and hearing are closely related to ET function in chronic ear disease patients. After successful tympanoplasty, restoration of a well-aerated middle ear with good ET function can permit better compliance of the tympanic membrane. In this study, we evaluated the predictive validity of preoperative ET function measurements.', 'We reviewed 137 patients who underwent type 1 tympanoplasty. All patients had non-cholesteatomatous chronic otitis media and received canal wall-up-type tympanomastoidectomies. Patients were categorized into four groups according to preoperative ET function measurements using a modified pressure inflation-deflation equilibration test. Group I patients had residual pressures less than 10 daPa, and Group IV patients showed no pressure change (poor results). Groups II and III were intermediate. Hearing levels were determined using pure tone averages at four frequencies. Postoperative tympanography was performed to determine middle ear aeration.', 'The preoperative air bone (AB) gap was 29.6+/-7.0 dB, and the postoperative gap was 16.5+/-5.7 dB; thus, there was significant overall improvement. In all groups, hearing was significantly better after surgery, but the worst postoperative hearing level was seen in Group IV patients. Type B tympanograms were more frequently recorded in Group IV patients than they were in Group I or II patients. Postoperative AB gaps were 9.2+/-3.8 dB in patients with type A tympanograms, 13.4+/-2.1 dB in those with type As, 24.1+/-2.5 dB in those with type C, and 18.5+/-2.8 dB in those with type B.",
            "output": [
                "Is pre-operative Evaluation of Eustachian Tube Function Using a Modified Pressure Equilibration Test Predictive of Good Postoperative Hearing and Middle Ear Aeration in Type 1 Tympanoplasty Patients?"
            ]
        },
        {
            "id": "task847-0bcdaaaa3da44d8485aa8cbfd8c449f3",
            "input": "Both BALB/c mice and common voles (Microtus arvalis) are considered highly susceptible to tularemia. However, the common vole is reported to harbour Francisella tularensis in European habitats as well as to survive longer with chronic shedding of the bacterium. The purpose of the present study was to compare the response of these two rodents to a wild Francisella tularensis subsp. holarctica strain infection.', 'Rodents were evaluated for differences in the total antioxidant capacity derived from low-molecular-weight antioxidants, biochemistry including lipid metabolism, tissue bacterial burdens and histopathology following experimental intraperitoneal infection with 160 colony forming units (CFU) pro toto.', 'Bacterial burdens in common voles started to develop later post-exposure and amounted to lower levels than in BALB/c mice. Elevation of liver function enzymes was more pronounced in mice than common voles and there were marked differences in lipid metabolism in the course of tularemia in these two species. Hypertriglyceridemia and hypercholesterolemia developed in mice, while physiologically higher levels of triglycerides and cholesterol showed a decreasing tendency in common voles. On the other hand, the total plasma antioxidant capacity gradually dropped to 81.5% in mice on day 5 post-infection, while it increased to 130% on day 6 post-infection in common voles. Significant correlations between tissue bacterial burdens and several biochemical parameters were found.",
            "output": [
                "Does tularemia induce different biochemical responses in BALB/c mice and common voles?"
            ]
        },
        {
            "id": "task847-73a1850dabc24fc5bc91b7572bc4655e",
            "input": "Determine the utility of optical coherence tomography (OCT) to detect clinical and subclinical remote optic neuritis (ON), its relationship to clinical characteristics of ON and visual function, and whether the retinal nerve fiber layer (RNFL) thickness functions as a surrogate marker of global disease severity.', 'Cross-sectional study of 65 subjects with at least 1 clinical ON episode at least 6 months prior. Measures included clinical characteristics, visual acuity (VA), contrast sensitivity (CS), OCT, and visual evoked potentials (VEP).', 'Ninety-six clinically affected optic nerves were studied. The sensitivity of OCT RNFL after ON was 60%, decreasing further with mild onset and good recovery. VEP sensitivity was superior at 81% (p = 0.002). Subclinical ON in the unaffected eye was present in 32%. VEP identified 75% of all subclinically affected eyes, and OCT identified <20%. RNFL thickness demonstrated linear correlations with VA (r = 0.65) and CS (r = 0.72) but was unable to distinguish visual categories <20/50. RNFL was thinner with severe onset and disease recurrence but was unaffected by IV glucocorticoids. OCT measurements were not related to overall disability, ethnicity, sex, or age at onset. The greatest predictor for RNFL in the unaffected eye was the RNFL in the fellow affected eye.",
            "output": [
                "Is optical coherence tomography less sensitive than visual evoked potentials in optic neuritis?"
            ]
        },
        {
            "id": "task847-2b41daebc99d4c00a80b21cd5b71cc8a",
            "input": "Accurate measurement of household food purchase behavior (HFPB) is important for understanding its association with household characteristics, individual dietary intake and neighborhood food retail outlets. However, little research has been done to develop measures of HFPB. The main objective of this paper is to describe the development of a measure of HFPB using annotated food purchase receipts.', 'Households collected and annotated food purchase receipts for a four-week period as part of the baseline assessment of a household nutrition intervention. Receipts were collected from all food sources, including grocery stores and restaurants. Households (n = 90) were recruited from the community as part of an obesity prevention intervention conducted in 2007-2008 in Minneapolis, Minnesota, USA. Household primary shoppers were trained to follow a standardized receipt collection and annotation protocol. Annotated receipts were mailed weekly to research staff. Staff coded the receipt data and entered it into a database. Total food dollars, proportion of food dollars, and ounces of food purchased were examined for different food sources and food categories. Descriptive statistics and correlations are presented.', 'A total of 2,483 receipts were returned by 90 households. Home sources comprised 45% of receipts and eating-out sources 55%. Eating-out entrees were proportionally the largest single food category based on counts (16.6%) and dollars ($106 per month). Two-week expenditures were highly correlated (r = 0.83) with four-week expenditures.",
            "output": [
                "Do annotated receipts capture household food purchases from a broad range of sources?"
            ]
        },
        {
            "id": "task847-f91d14d935f64f6ba6f019ebd0809b5e",
            "input": "Lafora disease (LD) is a fatal autosomal recessive neurodegenerative disease. A hallmark of LD is cytoplasmic accumulation of insoluble glucans, called Lafora bodies (LBs). Mutations in the gene encoding the phosphatase laforin account for approximately 50% of LD cases, and this gene is conserved in all vertebrates. We recently demonstrated that laforin is the founding member of a unique class of phosphatases that dephosphorylate glucans.', 'Herein, we identify laforin orthologs in a protist and two invertebrate genomes, and report that laforin is absent in the vast majority of protozoan genomes and it is lacking in all other invertebrate genomes sequenced to date. We biochemically characterized recombinant proteins from the sea anemone Nematostella vectensis and the amphioxus Branchiostoma floridae to demonstrate that they are laforin orthologs. We demonstrate that the laforin gene has a unique evolutionary lineage; it is conserved in all vertebrates, a subclass of protists that metabolize insoluble glucans resembling LBs, and two invertebrates. We analyzed the intron-exon boundaries of the laforin genes in each organism and determine, based on recently published reports describing rates of molecular evolution in Branchiostoma and Nematostella, that the conservation of laforin is linked to the molecular rate of evolution and the glucan metabolism of an organism.",
            "output": [
                "Is conservation of the glucan phosphatase laforin linked to rates of molecular evolution and the glucan metabolism of the organism?"
            ]
        },
        {
            "id": "task847-ab15257228db410091ab9321408e0a89",
            "input": "To determine the prognostic role of co-morbidity in medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT).', \"Between 2000 and 2007, 88 consecutive early-stage medically inoperable NSCLC patients were treated by linac-based SBRT. The dose was either 45 Gy or 67.5 Gy in three fractions prescribed to the isocenter. Baseline co-morbidities were retrospectively retrieved by consultation of a formal electronic registry of diagnoses as well as patients' charts. The age-adjusted Charlson Co-morbidity Index (CCI) was scored for each patient and subjected to univariate and multivariate analysis.\", 'With a median follow-up of 44 months, the actuarial local control rate at 4 years was 89% while the median overall survival was 22 months. The median age-adjusted CCI score was 5. The age-adjusted CCI was a significant predictor of overall survival on both univariate (p=0.002) and multivariate analysis (p=0.011). Patients with an age-adjusted CCI score of 3 or less had a median survival of 41 months versus only 11 months for those scoring 6 or more.",
            "output": [
                "Does co-morbidity index predict for mortality after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-88a57b2a57e1411a996bf81fca4c6b1b",
            "input": "We investigated whether serum vascular endothelial growth factor (VEGF) levels in acute-stage ischaemic stroke patients with small vessel disease (SVD) or large vessel disease (LVD) are correlated with long-term prognoses, based on the difference in NIH Stroke Scale (NIHSS) scores between acute and chronic stages.', 'From March 2007 to May 2008, we evaluated patients who experienced an ischaemic stroke for the first time, defined as SVD (n = 89) or LVD (n = 91) using the TOAST classification. Serum samples were taken immediately after admission (within 24 h of stroke onset) to evaluate VEGF levels. After 3 months, follow-up NIHSS scores were collected for all patients.', 'Serum VEGF levels in the acute stage (within 24 h of stroke onset) were higher in the LVD group than in the SVD group and were correlated with infarction volume. The increase in serum VEGF levels in the acute stage was proportional to an improved NIHSS score after 3 months. After adjustment for covariates, serum VEGF levels in the acute stage were still significantly correlated with the long-term prognosis of ischaemic stroke.",
            "output": [
                "Are serum VEGF levels in acute ischaemic strokes correlated with long-term prognosis?"
            ]
        },
        {
            "id": "task847-59c8157702f14be09469972aec97d6bd",
            "input": "The aim of this study was to determine the accuracy of new quantitative echocardiographic strain and strain-rate imaging parameters to identify abnormal regional right ventricular (RV) deformation associated with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C).', 'A total of 34 patients with ARVD/C (confirmed by Task Force criteria) and 34 healthy controls were prospectively enrolled. Conventional echocardiography, including Doppler tissue imaging (DTI), was performed. Doppler and two-dimensional strain-derived velocity, strain, and strain rate were calculated in the apical, mid, and basal segments of the RV free wall.', 'RV dimensions were significantly increased in patients with ARVD/C (RV outflow tract 19.3+/-5.2 mm/m2 vs 14.1+/-2.2 mm/m2, P<.001; RV inflow tract 23.4+/-4.8 mm/m2 vs 18.8+/-2.4 mm/m2, P<.001), whereas left ventricular dimensions were not significantly different compared with controls. Strain and strain rate values were significantly lower in patients with ARVD/C in all 3 segments. All deformation parameters showed a higher accuracy to detect functional abnormalities compared with conventional echocardiographic criteria of dimensions or global systolic function. The lowest DTI strain value in any of the 3 analyzed segments showed the best receiver operating characteristics (area under the curve 0.97) with an optimal cutoff value of -18.2%.",
            "output": [
                "Does echocardiographic tissue deformation imaging quantify abnormal regional right ventricular function in arrhythmogenic right ventricular dysplasia/cardiomyopathy?"
            ]
        },
        {
            "id": "task847-bf058ff43adf492581d858b4347995da",
            "input": "The goal was to assess the impact of influenza vaccine clinical alerts on missed opportunities for vaccination and on overall influenza immunization rates for children and adolescents with asthma.', 'A prospective, cluster-randomized trial of 20 primary care sites was conducted between October 1, 2006, and March 31, 2007. At intervention sites, electronic health record-based clinical alerts for influenza vaccine appeared at all office visits for children between 5 and 19 years of age with asthma who were due for vaccine. The proportion of captured immunization opportunities at visits and overall rates of complete vaccination for patients at intervention and control sites were compared with those for the previous year, after standardization for relevant covariates. The study had >80% power to detect an 8% difference in the change in rates between the study and baseline years at intervention versus control practices.', 'A total of 23 418 visits and 11 919 children were included in the study year and 21 422 visits and 10 667 children in the previous year. The majority of children were male, 5 to 9 years of age, and privately insured. With standardization for selected covariates, captured vaccination opportunities increased from 14.4% to 18.6% at intervention sites and from 12.7% to 16.3% at control sites, a 0.3% greater improvement. Standardized influenza vaccination rates improved 3.4% more at intervention sites than at control sites. The 4 practices with the greatest increases in rates (>or=11%) were all in the intervention group. Vaccine receipt was more common among children who had been vaccinated previously, with increasing numbers of visits, with care early in the season, and at preventive versus acute care visits.",
            "output": [
                "Does impact of electronic health record-based alert on influenza vaccination for children with asthma?"
            ]
        },
        {
            "id": "task847-5483195d982c446f905a2e342a2bc395",
            "input": "The effects of GH on exercise performance remain unclear.', 'The aim of the study was to examine the effects of GH receptor (GHR) antagonist treatment on exercise performance.', 'Subjects were treated with the GHR antagonist pegvisomant or placebo for 16 d. After the treatment period, they exercised to determine exercise performance and hormonal and metabolic responses.', 'Twenty healthy males participated in the study.', 'Subjects were treated with the GHR antagonist (n = 10; 10 mg/d) or placebo (n = 10). After the treatment period, they performed a maximal oxygen uptake (VO(2 max)) test and a prolonged exercise test, consisting of 60 min of submaximal cycling followed by exercise to fatigue at 90% of VO(2 max).', 'VO(2 max) was measured before and after the treatment period. Hormonal and metabolic responses and time to exhaustion during prolonged exercise were determined.', 'Resting serum IGF-I concentration decreased by 20% in the GHR antagonist-treated group (P < 0.05), whereas no change was observed in the placebo group. Conversely, resting serum GH concentration was significantly higher in the treatment group compared with the placebo group (P < 0.01). VO(2 max) did not change significantly in either group after the treatment period. Time to exhaustion at 90% of VO(2 max) was significantly shorter in the treatment group (P < 0.05). No significant differences were observed between the groups in terms of changes in serum free fatty acids, glycerol, VO(2), or relative fat oxidation.",
            "output": [
                "Does growth hormone receptor antagonist treatment reduce exercise performance in young males?"
            ]
        },
        {
            "id": "task847-d4c4890dcf114dea879e1029bd730926",
            "input": "We questioned whether infection with murine gammaherpesvirus 68 (HV-68) might exacerbate inflammatory bowel disease using mice deficient in IL-10 (IL-10-/-) as a model of developing colitis.', 'Groups of C57BL/6 mice and IL-10-/- mice were mock-treated or infected with HV-68. Two months following infection, mice were euthanized and a variety of parameters were measured to quantify the extent of inflammation and the presence of virus. Measurements included survival, body weight, splenomegaly, colonic disease scores, liver histopathology, viable bacteria in the liver, and splenic viral burden.', 'IL-10-/- mice infected with HV-68 displayed reduced survival, lower body weights, increased splenomegaly, exacerbated colonic disease scores, increased numbers of viable bacteria in the liver, and increased leukocyte liver infiltration when compared to mock-treated IL-10-/- mice or HV-68 infected C57BL/6 mice. Surprisingly, levels of infectious or latent virus were not significantly different between the groups of mice exposed to HV-68.",
            "output": [
                "Does infection with murine gammaherpesvirus 68 exacerbate inflammatory bowel disease in IL-10-deficient mice?"
            ]
        },
        {
            "id": "task847-c96173d936fd4c0c8a5924d49846610c",
            "input": "The proteasome is the proteolytically active core of the ubiquitin-proteasome system, which regulates vital processes and which can cause various diseases when it malfunctions. Therefore, the proteasome has become an attractive target for pharmaceutical interventions. Inhibition of the cardiac proteasome by specific proteasome inhibitors has been shown to attenuate cardiac hypertrophy and ischaemia reperfusion injury of the heart. We have resolved the cardiac proteasome into its subtypes and have addressed the key question of how proteasome inhibitors affect single cardiac proteasomal subtypes.', 'The 20S proteasome from rat heart was dissected into three different subpopulations (groups I-III), each comprising 4-7 different subtypes. The major group (group II) comprises standard proteasome subtypes; the two minor subpopulations (groups I and III) contain intermediate proteasome subtypes. All subtypes exhibit chymotrypsin-, trypsin-, and caspase-like activity but to different degrees. We have tested the effect of two common proteasome inhibitors on the chymotrypsin-like activity of all subtypes: 20-30 nmol/L MG132 caused 50% inhibition of all subtypes from groups I and II, whereas 100 nmol/L was necessary to affect group III subtypes to the same extent. However, another inhibitor, bortezomib (VELCADE), already used clinically, inhibited 50% of the activity of group III proteasome subtypes even below 20 nmol/L, a concentration showing almost no effect on group I and II proteasome subtypes. The caspase-like activity of group II proteasome subtypes was not affected by MG132 and was inhibited by bortezomib only at concentrations above 100 nmol/L.",
            "output": [
                "Do multiple cardiac proteasome subtypes differ in their susceptibility to proteasome inhibitors?"
            ]
        },
        {
            "id": "task847-c9511496e3a64ef7aee13a55aaaa1466",
            "input": "Increased intracranial pressure induces neurogenic pulmonary edema (NPE), potentially explaining why only lungs from less than 20% of brain dead organ donors can be used for transplantation. This study investigated the underlying mechanisms of NPE, focusing on neuropeptides, which potently induce vasoconstriction, vasodilatation, and neurogenic inflammation.', 'Brain death was induced in 10 pigs by increasing the intracranial pressure. Eight additional pigs served as controls. Neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and substance P were analyzed in plasma, bronchoalveolar lavage (BAL) fluid, and homogenized lung tissue 6 hours after brain death. Pulmonary oxygen exchange was estimated using partial pressure of arterial oxygen (Pao2)/fraction of inspired oxygen (Fio2), and pulmonary edema by wet/dry weight ratio.', 'Brain death induced a decrease in Pao(2)/Fio2 (p < 0.001) and increased the wet/dry weight of both apical (p = 0.01) and basal lobes (p = 0.03). NPY and CGRP concentrations were higher in the BAL fluid of brain-dead animals compared with controls (p = 0.02 and p = 0.02) and were positively correlated with the wet/dry weight ratio. NPY content in lung tissue was lower in brain-dead animals compared with controls (p = 0.04) and was negatively correlated with the wet/dry weight ratio. There were no differences in substance P concentrations between the groups.",
            "output": [
                "Does alteration of neuropeptides in the lung tissue correlate brain death-induced neurogenic edema?"
            ]
        },
        {
            "id": "task847-0c4ffb6f7d284f65aed7ddf0537ee421",
            "input": "We developed a mouse model that enables non-invasive assessment of changes in beta cell mass.', 'We generated a transgenic mouse expressing luciferase under control of the mouse insulin I promoter [mouse insulin promoter-luciferase-Vanderbilt University (MIP-Luc-VU)] and characterized this model in mice with increased or decreased beta cell mass and after islet transplantation.', 'Streptozotocin-induced, diabetic MIP-Luc-VU mice had a progressive decline in bioluminescence that correlated with a decrease in beta cell mass. MIP-Luc-VU animals fed a high-fat diet displayed a progressive increase in bioluminescence that reflected an increase in beta cell mass. MIP-Luc-VU islets transplanted beneath the renal capsule or into the liver emitted bioluminescence proportional to the number of islets transplanted and could be imaged for more than a year.",
            "output": [
                "Does bioluminescence imaging in mouse models quantify beta cell mass in the pancreas and after islet transplantation?"
            ]
        },
        {
            "id": "task847-d6118eb273de430db1be5a44c308acae",
            "input": "The influence of different types of exercise on risk factors for cardiovascular diseases has rarely been investigated. The aim of the present work was to evaluate the effect of adding resistance exercise to aerobic activities on lipid-lipoprotein profile, in a representative sample of men and women from the province of Attica, Greece.', 'We randomly enrolled 1514 and 1528 healthy men and women, respectively, stratified by city, age and gender distribution. Participants were classified as inactive (INA), sufficiently active (SA) and highly active for either aerobic activities (HAA) alone or a combination of aerobic plus resistance exercise (HAC). The main outcome measures are lipid-lipoprotein profile [total, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein-A1, apolipoprotein-B] and anthropometric indices.', 'From those participating in aerobic activities, 480 (31.7%) men and 502 (32.9%) women were classified as SA, 100 men (6.6%) and 93 women (6.1%) as HAA and 90 men (5.9%) and 49 women (3.2%) as HAC. After various adjustments were made, men from the HAC group had an average of 23% lower plasma triacylglycerol concentration (P = 0.04) and 10% lower LDL-cholesterol (P = 0.01) when compared with the HAA group. Moreover, women from the HAC group had 13% lower LDL-cholesterol when compared with HAA group (P = 0.051).",
            "output": [
                "Is resistance exercise plus to aerobic activities associated with better lipids ' profile among healthy individuals : the ATTICA study?"
            ]
        },
        {
            "id": "task847-60e3b8de381a4a038ccc746e416c6048",
            "input": "To improve prostate cancer (PC) detection accuracy among patients with a prostate-specific antigen (PSA) above 4.0 ng/ml and asymptomatic prostate inflammation.', 'A total of 136 patients with PSA ranging from 4.0 to 50.0 ng/ml with asymptomatic prostatitis were included in the study cohort. All these patients underwent antibacterial therapy for 2 weeks followed by repeat PSA determination and transrectal ultrasound-guided needle prostate biopsy. The PSA, PSAD (PSA density), and f/t PSA (free/total PSA) before and after antibacterial therapy were compared using t-test. The receiver-operating characteristic (ROC) technique was used to evaluate the effectiveness of PSA, PSAD, f/t PSA, and their changes after antibacterial therapy (DeltaPSA, DeltaPSAD, and Deltaf/t PSA) on PC detection.', 'Among the 136 patients, 33 had PC and the other 103 histologically confirmed benign prostatic disease. After antibacterial therapy for 2 weeks, the PSA (mean +/- standard deviation) decreased from 14.0 +/- 7.8 ng/ml to 10.4 +/- 7.7 ng/ml (P < 0.01). The DeltaPSA, DeltaPSAD, and Deltaf/tPSA were -3.60 +/- 4.3 ng/ml, -0.1 +/- 0.1 ng/ml/ml, and -0.1 +/- 0.1 respectively. The areas under ROC curve were 0.29 for PSA, 0.64 for PSAD, and 0.50 for f/t PSA. The areas under ROC curve were 0.91 for DeltaPSA, 0.96 for DeltaPSAD, and 0.98 for Deltaf/t PSA. These values were increased significantly when compared with those for the PSA-related parameters before antibacterial therapy (P value, DeltaPSA, DeltaPSAD, and Deltaf/t PSA were <0.01).",
            "output": [
                "Does antibacterial therapy improve the effectiveness of prostate cancer detection using prostate-specific antigen in patients with asymptomatic prostatitis?"
            ]
        },
        {
            "id": "task847-414f3f34801546bdba3dfd5264cc4f28",
            "input": "We examined the effects of cilostazol on mitogen-activated protein kinase (MAPK) activity and its relationship with cilostazol-mediated protection against apoptosis in lipopolysaccharide (LPS)-treated endothelial cells.', 'Human umbilical vein endothelial cells (HUVECs) were exposed to LPS and cilostazol with and without specific inhibitors of MAPKs; changes in MAPK activity in association with cell viability and apoptotic signaling were investigated.', 'Cilostazol protected HUVECs against LPS-induced apoptosis by suppressing the mitochondrial permeability transition, cytosolic release of cytochrome c, and subsequent activation of caspases, stimulating extracellullar signal-regulated kinase (ERK1/2) and p38 MAPK signaling, and increasing phosphorylated cAMP-responsive element-binding protein (CREB) and Bcl-2 expression, while suppressing Bax expression. These cilostazol-mediated cellular events were effectively blocked by MAPK/ERK kinase (MEK1/2) and p38 MAPK inhibitors.",
            "output": [
                "Does cilostazol protect endothelial cells against lipopolysaccharide-induced apoptosis through ERK1/2- and P38 MAPK-dependent pathways?"
            ]
        },
        {
            "id": "task847-e2fd3297fa914cb8a62c02a3fe235e9a",
            "input": "The peptidyl-proline isomerase, Protein Never in Mitosis Gene A Interacting-1 (PIN1), regulates turnover of inducible nitric oxide synthase (iNOS) in murine aortic endothelial cells (MAEC) stimulated with E. coli endotoxin (LPS) and interferon-gamma (IFN). Degradation of iNOS was reduced by a calpain inhibitor, suggesting that PIN1 may affect induction of other calpain-sensitive inflammatory proteins, such as cyclooxygenase (COX)-2, in MAEC.', 'MAEC, transduced with lentivirus encoding an inactive control short hairpin (sh) RNA or one targeting PIN1 that reduced PIN1 by 85%, were used. Cells were treated with LPS/IFN, calpain inhibitors (carbobenzoxy-valinyl-phenylalaninal (zVF), PD150606), cycloheximide and COX inhibitors to determine the effect of PIN1 depletion on COX-2 and calpain.', 'LPS or IFN alone did not induce COX-2. However, treatment with 10 mug LPS plus 20 ng IFN per ml induced COX-2 protein 10-fold in Control shRNA MAEC. Induction was significantly greater (47-fold) in PIN1 shRNA cells. COX-2-dependent prostaglandin E2 production increased 3-fold in KD MAEC, but did not increase in Control cells. The additional increase in COX-2 protein due to PIN1 depletion was post-transcriptional, as induction of COX-2 mRNA by LPS/IFN was the same in cells containing or lacking PIN1. Instead, the loss of COX-2 protein, after treatment with cycloheximide to block protein synthesis, was reduced in cells lacking PIN1 in comparison with Control cells, indicating that degradation of the enzyme was reduced. zVF and PD150606 each enhanced the induction of COX-2 by LPS/IFN. zVF also slowed the loss of COX-2 after treatment with cycloheximide, and COX-2 was degraded by exogenous mu-calpain in vitro. In contrast to iNOS, physical interaction between COX-2 and PIN1 was not detected, suggesting that effects of PIN1 on calpain, rather than COX-2 itself, affect COX-2 degradation. While cathepsin activity was unaltered, depletion of PIN1 reduced calpain activity by 55% in comparison with Control shRNA cells.",
            "output": [
                "Does protein Never in Mitosis Gene A Interacting-1 regulate calpain activity and the degradation of cyclooxygenase-2 in endothelial cells?"
            ]
        },
        {
            "id": "task847-0fb4e6b2d3bc4203b7d352a47366d2f4",
            "input": "The systemic injection of neural stem/precursor cells (NPCs) provides remarkable amelioration of the clinico-pathological features of experimental autoimmune encephalomyelitis (EAE). This is dependent on the capacity of transplanted NPCs to engage concurrent mechanisms of action within specific microenvironments in vivo. Among a wide range of therapeutic actions alternative to cell replacement, neuroprotective and immune modulatory capacities of transplanted NPCs have been described. However, lacking is a detailed understanding of the mechanisms by which NPCs exert their therapeutic plasticity. This study was designed to identify the first candidate that exemplifies and sustains the immune modulatory capacity of transplanted NPCs.', 'To achieve the exclusive targeting of the peripheral immune system, SJL mice with PLP-induced EAE were injected subcutaneously with NPCs and the treatment commenced prior to disease onset. NPC-injected EAE mice showed significant clinical improvement, as compared to controls. Exogenous NPCs lacking the expression of major neural antigens were reliably (and for long-term) found at the level of draining lymph nodes, while establishing sophisticated anatomical interactions with lymph node cells. Importantly, injected NPCs were never found in organs other than lymph nodes, including the brain and the spinal cord. Draining lymph nodes from transplanted mice showed focal up-regulation of major developmental stem cell regulators, such as BMP-4, Noggin and Sonic hedgehog. In lymph nodes, injected NPCs hampered the activation of myeloid dendritic cells (DCs) and steadily restrained the expansion of antigen-specific encephalitogenic T cells. Both ex vivo and in vitro experiments identified a novel highly NPC-specific-BMP-4-dependent-mechanism hindering the DC maturation.",
            "output": [
                "Do immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function?"
            ]
        },
        {
            "id": "task847-b76801593b3d4ca782beb63f2268300e",
            "input": "To evaluate the effect of topical N-acetylcysteine (NAC) on interleukin 1-alpha (IL-1alpha) levels in tear fluid after myopic laser subepithelial keratectomy (LASEK) and its possible role in modulating corneal wound healing.', 'Twenty-six eyes of 13 patients who underwent myopic LASEK were divided into 2 groups. Group 1 (n=10 eyes) was used as a control group. All patients received topical lomefloxacin and dexamethasone postoperatively. Additionally, patients in Group 2 received topical NAC for 1 month postoperatively. Tear fluid samples were collected with microcapillary tubes preoperatively, on the first and on the fifth postoperative day, and the release of IL-1alpha in tear fluid was calculated. Haze grading and confocal microscopic examination were performed at 1 and 3 months postoperatively.', 'The mean IL-1-alpha release values were 0.285-/+0.159 pg/min in Group 1 and 0.235-/+0.142 pg/min in Group 2 preoperatively. In Group 1, the values were 0.243-/+0.155 pg/min on day 1 and 0.164-/+0.125 pg/min on day 5. In Group 2, the mean IL-1alpha release values were 0.220-/+0.200 pg/min on day 1 and 0.080-/+0.079 pg/min on day 5. The difference between the groups was significant only for day 5 (p<0.05). Mean corneal haze score and grey scale value in confocal microscopy were significantly higher (p<0.05) in Group 1 at 1 month. However, at 3 months there was no difference between groups (p>0.05).",
            "output": [
                "Does topical N-acetylcysteine reduce interleukin-1-alpha in tear fluid after laser subepithelial keratectomy?"
            ]
        },
        {
            "id": "task847-709dedb08d1045b28eec797b96de2c70",
            "input": "Most patients with Fusarium infection present with affection of the tegumentary system, with the presence of necrotic and/or inflammatory lesions associated with pain.', 'To evaluate the effect of the intradermal application of a metabolic extract of Fusarium oxysporum in the skin of Wistar rats.', 'The extract was obtained from fungal cultivation in Czapek-Dox medium. It was sterilized by filtration through a Millipore membrane, and injected (0.5 mg/mL) intradermally into the skin of rats, which were killed 3, 6, 12, and 24 h after inoculation. Skin specimens were placed in paraffin and stained using hematoxylin and eosin, and toluidine blue, for the evaluation of the inflammatory response, and Sirius red for the quantification of collagen. Terminal deoxynucleotidyl transferase-mediated UTP nick end labelling (TUNEL) was used for the identification of apoptosis. Tissue reactions were graded and compared over time and compartment.', 'The inflammatory reaction reached a peak at 12 h for both the dermis and subcutaneous region, being graded as moderate and moderate to severe, respectively. There was an influx of granulocytes, lymphocytes, and macrophages. A significant increase in the number of mast cells, as well as the presence of hyperemic vessels and apoptotic bodies, was observed. There was TUNEL staining in keratinocytes, fibroblasts, endothelial cells, muscles, and in the cells of the inflammatory infiltrate. There was a significant decrease in the area occupied by collagen after 12 h.",
            "output": [
                "Does metabolic extract of Fusarium oxysporum induce histopathologic alterations and apoptosis in the skin of Wistar rats?"
            ]
        },
        {
            "id": "task847-5d4d19ed9e04419c9e59f9edfe09e950",
            "input": "Autologous hematopoietic stem cell transplantation (HSCT) has recently become a novel therapy for patients with new-onset type 1 diabetes (T1D). However, the optimal time points for HSCT are still unknown.', 'By using multiple low-dose streptozotocin (STZ)-induced T1D mice models, we performed syngeneic bone marrow transplantation (syn-BMT) in diabetic mice at various time points new-onset day 3 (n = 12); new-onset day 10 (n = 13); later-onset day 20 (n = 12); and day 40 (n = 7), respectively. At 120 days after syn-BMT, we examined pancreata histology, serum insulin, and CD4(+)CD25(+)FoxP3(+) T regulatory lymphocytes (Tregs).', 'Our previous results showed that syn-BMT can overcome diabetes when performed on day 10, but not at day 40. Our new data showed BMT only attenuated diabetes when done on day 3 or day 20. Moreover, the percentage of Tregs in the spleen correlated with the attenuation of hyperglycemia.",
            "output": [
                "Is time point important for effects of syngeneic bone marrow transplantation for type 1 diabetes in mice?"
            ]
        },
        {
            "id": "task847-e81198cf2529460a939dc8e3db476655",
            "input": "Dysphagia is a leading complication in stroke patients causing aspiration pneumonia, malnutrition and increased mortality. Current strategies of swallowing therapy involve on the one hand modification of eating behaviour or swallowing technique and on the other hand facilitation of swallowing with the use of pharyngeal sensory stimulation. Thermal tactile oral stimulation (TTOS) is an established method to treat patients with neurogenic dysphagia especially if caused by sensory deficits. Little is known about the possible mechanisms by which this interventional therapy may work. We employed whole-head MEG to study changes in cortical activation during self-paced volitional swallowing in fifteen healthy subjects with and without TTOS. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of individual SAM data was performed using a permutation test.', 'Compared to the normal swallowing task a significantly increased bilateral cortical activation was seen after oropharyngeal stimulation. Analysis of the chronological changes during swallowing suggests facilitation of both the oral and the pharyngeal phase of deglutition.",
            "output": [
                "Does tactile thermal oral stimulation increase the cortical representation of swallowing?"
            ]
        },
        {
            "id": "task847-c137c7c478754dcaa75bea837470bd9c",
            "input": "Primary percutaneous coronary intervention (PCI) is more effective than fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI), but initial treatment delay to intervention is the main limitation of this strategy.', 'Upstream use of high-dose tirofiban could reduce myocardial infarct size, using analysis of contrast-enhanced magnetic resonance imaging (CE-MRI).', 'Patients with STEMI within 12 hours after symptom onset were randomized to a facilitated PCI group (n = 19) or to a primary PCI group (n = 20). The primary endpoint was myocardial infarct size evaluated by the volume of delayed hyperenhancement on CE-MRI at 1 month after index procedure.', 'The baseline clinical characteristics were not significantly different between the 2 groups. Although the incidence of pre-PCI thrombolysis in myocardial infarction (TIMI) flow grade 2 to 3 was significantly higher in the facilitated PCI group than in the primary PCI group (47.4% vs 15.0%, P = 0.03), the achievement of myocardial blush grade 2 to 3 or ST-segment resolution at 30 minutes after procedure was not significantly different between the facilitated PCI and the primary PCI group (36.8% vs 40%, P = 0.84 and 31.6% vs 20%, P = 0.41, respectively). Infarct size on CE-MRI was similar in the facilitated PCI group and the conventional primary PCI group (22.1% +/- 11.7% vs 25.2% +/- 13.2%, P = 0.44). At 6 months, the left ventricular ejection fraction (LVEF) on echocardiography was 52.6% +/- 10.4% in the facilitated PCI group and 50.9% +/- 9.8% in the primary PCI group (P = 0.68).",
            "output": [
                "Does upstream high-dose tirofiban reduce myocardial infarct size in patients undergoing primary percutaneous coronary intervention : a magnetic resonance imaging pilot study?"
            ]
        },
        {
            "id": "task847-14f9b519b377444c87decc3d225246a6",
            "input": "This study examines the physiologic effects of theraputic plasma exchange (TPE) in the setting of refractory burn shock and attempts to identify variables that correlate with the eventual need for TPE.', \"A retrospective analysis was conducted of 40 patients over 24 months with >20% TBSA burns who experienced complicated resuscitations. TPE was utilized in 21 patients when the patients' total resuscitation volumes exceeded 1.2 times the amount predicted by the modified Baxter formula (3 cm(3) LR/kg/%TBSA). Nineteen matched, contemporaneous patients served as controls. Demographic, injury severity, and acute clinical variables were abstracted for comparison between the two groups. Additionally, the TPE group was analyzed for blood lactate levels, mean arterial pressure (MAP) and urine output (UOP) before and after TPE. Univariate and multivariate statistical analyses were used for comparisons, where appropriate.\", 'In response to TPE, MAP increased by 24% (p<0.0001), UOP increased by >400% (p=<0.0001), IVF rates were reduced by 25% (p=0.01), and lactate levels decreased by almost 50% (p=0.0006). On univariate analysis, admission lactate (p=0.0006) and %TBSA (p=0.01) were found to be significantly increased in the TPE group compared to controls, while there was no difference in age, gender, weight, admission HCT, incidence of acute renal failure, or mortality between the groups. However, on multivariate logistic regression analysis, only elevated admission lactate was independently associated with the eventual need for TPE (OR 2.23, 95% CI=1.30-3.84, p=0.004).",
            "output": [
                "Do the use of theraputic plasma exchange ( TPE ) in the setting of refractory burn shock?"
            ]
        },
        {
            "id": "task847-0082dbe3ae11475b8f5563724fcce4d0",
            "input": "Arginine vasopressin is a vasoactive drug commonly used in distributive shock states including mixed shock with a cardiac component. However, the direct effect of arginine vasopressin on the function of the ischemia/reperfusion injured heart has not been clearly elucidated.', 'We measured left ventricular ejection fraction using trans-thoracic echocardiography in C57B6 mice, both in normal controls and following ischemia/reperfusion injury induced by a one hour ligation of the left anterior descending coronary artery. Mice were treated with one of normal saline, dobutamine (8.33 microg/kg/min), or arginine vasopressin (0.00057 Units/kg/min, equivalent to 0.04 Units/min in a 70 kg human) delivered by an intraperitoneal micro-osmotic pump. Arterial blood pressure was measured using a micromanometer catheter. In addition, mortality was recorded and cardiac tissues processed for RNA and protein.', 'Baseline left ventricular ejection fraction was 65.6% (60 to 72). In normal control mice, there was no difference in left ventricular ejection fraction according to infusion group. Following ischemia/reperfusion injury, AVP treatment significantly reduced day 1 left ventricular ejection fraction 46.2% (34.4 to 52.0), both in comparison with baseline and day 1 saline treated controls 56.9% (42.4 to 60.2). There were no significant differences in preload (left ventricular end diastolic volume), afterload (blood pressure) or heart rate to account for the effect of AVP on left ventricular ejection fraction. The seven-day mortality rate was highest in the arginine vasopressin group. Following ischemia/reperfusion injury, we found no change in cardiac V1 Receptor expression but a 40% decrease in Oxytocin Receptor expression.",
            "output": [
                "Does low-dose vasopressin infusion result in increased mortality and cardiac dysfunction following ischemia-reperfusion injury in mice?"
            ]
        },
        {
            "id": "task847-ec5b8b79a74c4394ab0e4d5a1735b44c",
            "input": "This study examined the correlation between P53 and vascular endothelial growth factor (VEGF) expression together with tumour vascularity and investigated their clinical significance in the prognosis of gastric carcinoma.', 'Ninety-five patients with gastric carcinoma who underwent curative surgical resection were studied using immunohistochemical staining. Correlation between the expression of p53, VEGF microvessel count (MVC) and various clinicopathologic factors were studied.', 'No significant correlation was found between p53 expression and clinicopathologic factors. The rate of VEGF positivity was significantly higher in patients with haematogenous metastasis than in those without haematogenous metastasis. Both p53 and VEGF expression were associated with MVC. The MVC in p53 positive tumours was significantly higher than that in p53 negative tumours. Similarly, the same trend was seen between VEGF expression and MVC. The p53 and VEGF were co-expressed in 61 of 95 tumours (64.2%), and a significant (p < 0.01) association between p53 and VEGF expressions was demonstrated. The rate of VEGF positivity was significantly (p < 0.01) higher in the patients with disease recurrence than in those without recurrence, whereas no significant correlation was found between disease recurrence and the expression of p53.",
            "output": [
                "Are p53 and vascular endothelial growth factor expressions two important indices for prognosis in gastric carcinoma?"
            ]
        },
        {
            "id": "task847-57f1e00ee51045d5b492b97b5bc70d4a",
            "input": "A higher anticholinergic risk score (ARS) is associated with an increased risk of anticholinergic adverse effects in elderly patients. It is unknown whether factors other than the use of anticholinergic drugs determine the ARS.', 'A comprehensive medical record review was conducted in 155 consecutive hospitalised patients (median age 79.0 years, interquartile range 66.0-86.0). Information was collected on: demographics; clinical characteristics (including medications and their doses); history of anticholinergic-induced adverse effects; and biochemical markers of hepatic and renal function (serum albumin concentrations and estimated glomerular filtration rate, eGFR). The ARS was calculated for each patient using a standard scoring approach and Poisson regression was used for identifying variables associated with the ARS.', 'Patients with an ARS >or= 3 had a lower eGFR (p = 0.012) and were receiving more non-anticholinergic drugs (p < 0.001) than patients with an ARS < 3. In addition to being prescribed more anticholinergic drugs, patients with ARS >or= 3 were prescribed high doses of these drugs more often than patients with ARS < 3 (41.3% vs. 26.9%, p = 0.034). A higher number of non-anticholinergic drugs (p < 0.001), a lower serum albumin concentration (p = 0.014), and a lower eGFR (p = 0.012) were independently associated with a higher ARS.",
            "output": [
                "Are hypoalbuminaemia and impaired renal function associated with increased anticholinergic drug prescribing?"
            ]
        },
        {
            "id": "task847-f19b8c9df988499d8088f9417f183927",
            "input": "Although the molecules involved in mitosis are becoming better characterized, we still lack an understanding of the emergent mechanical properties of the mitotic spindle. For example, we cannot explain how spindle length is determined. To gain insight into how forces are generated and responded to in the spindle, we developed a method to apply controlled mechanical compression to metaphase mitotic spindles in living mammalian cells while monitoring microtubules and kinetochores by fluorescence microscopy.', 'Compression caused reversible spindle widening and lengthening to a new steady state. Widening was a passive mechanical response, and lengthening was an active mechanochemical process requiring microtubule polymerization but not kinesin-5 activity. Spindle morphology during lengthening and drug perturbations suggested that kinetochore fibers are pushed outward by pole-directed forces generated within the spindle. Lengthening of kinetochore fibers occurred by inhibition of microtubule depolymerization at poles, with no change in sliding velocity, interkinetochore stretching, or kinetochore dynamics.",
            "output": [
                "Does compression regulate mitotic spindle length by a mechanochemical switch at the poles?"
            ]
        },
        {
            "id": "task847-d57eb2084a744e67823452a42849f7d2",
            "input": "To examine the relationship between cardiovascular fitness (VO(2)max) and abdominal obesity (waist circumference) and individual cardiovascular disease (CVD) risk factors, as well as a clustered risk factor profile, and to study the impact of gender, age and smoking on these relationships.', 'Cross-sectional.', 'Astrand Laboratory of Work Physiology, Swedish School of Sport and Health Sciences, Stockholm, Sweden.', 'Men (n = 781) and women (n = 890) from two random population-based samples of Swedish women and men aged 20 to 65 years.', 'Odds ratios.', 'Each unit of higher fitness was associated with a decrease in all individual risk factors ranging from 2% to 4% independent of waist circumference, each unit of higher waist circumference was associated with an increased risk ranging from 2% to 5% independent of fitness. For clustering of three or more of the risk factors, each unit of fitness was associated with a 5% decrease in risk and each unit of waist circumference with a 5% increase in risk. The clustered risk was higher in unfit participants who were older or smoked daily, regardless of waist circumference. Obese participants were at higher risk if they were men or older, regardless of fitness level. However, neither a higher fitness level nor lean status reduced the risk associated with smoking.",
            "output": [
                "Are fitness and abdominal obesity independently associated with cardiovascular risk?"
            ]
        },
        {
            "id": "task847-96e0154b63be4b19983e10ba60294a86",
            "input": "Cigarette smoking is an established risk factor for pancreatic cancer, but there is conflicting evidence regarding the effects of alcohol consumption. The effects of cigarettes and alcohol on age of sporadic pancreatic cancer diagnosis have not been examined; we evaluated the independent and synergistic effects of lifetime cigarette smoking and alcohol consumption on age at pancreatic cancer diagnosis in the United States.', 'We analyzed data on cigarette smoking and alcohol consumption from the IMPAC Services, Inc Cancer Information Resource File (CIRF), collected from June 1, 1993, to December 31, 2003, for 29,239 reported, histologically confirmed cases of pancreatic adenocarcinoma. We also analyzed data on cigarette smoking and alcohol consumption for 820 histologically confirmed cases of pancreatic adenocarcinoma from the University of Michigan Pancreatic Cancer Registry (UMPCR), collected from January 2004 to October 2007.', 'Current cigarette smokers were diagnosed at significantly younger ages than never smokers, according to data from the CIRF and UMPCR (8.3 and 6.3 y, respectively); the UMPCR data indicated dose effects. Past and current alcohol consumption were associated with younger age at diagnosis in both databases. Current smokers who were current drinkers were diagnosed significantly earlier (CIRF, 10.2 y; UMPCR, 8.6 y) than abstainers. Past cigarette smoking was associated modestly with younger diagnosis age.",
            "output": [
                "Do pancreatic cancer patients who smoke and drink are diagnosed at younger ages?"
            ]
        },
        {
            "id": "task847-6b607e8900494bdbad3d713176833937",
            "input": "Growth-differentiation factor-15 (GDF-15) is emerging as an independent prognostic biomarker in patients with cardiovascular (CV) disease. Little is known about the pathophysiological basis for the close association of GDF-15 to future CV events. We hypothesized that GDF-15 is related to underlying CV pathologies.', 'To relate the levels of GDF-15 to indices of CV dysfunction and disease in elderly individuals, serum levels of GDF-15 were measured in 1004 subjects aged 70 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Carotid intima-media thickness and plaque burden, and left ventricular (LV) geometry and function were assessed by ultrasound. Endothelial function was evaluated in forearm resistance vessels and in the brachial artery by venous occlusion plethysmography and ultrasound imaging, respectively. Elevated levels of GDF-15 were related to several CV risk factors (male gender, current smoking, body mass index, waist circumference, diabetes, fasting glucose, triglycerides, and low HDL cholesterol). After adjustment for CV risk factors, increased levels of GDF-15 were associated with reduced endothelium-dependent vasodilation in resistance vessels, plaque burden, LV mass and concentric LV hypertrophy, reduced LV ejection fraction, and clinical manifestations of coronary artery disease and heart failure.",
            "output": [
                "Is growth-differentiation factor-15 an independent marker of cardiovascular dysfunction and disease in the elderly : results from the Prospective Investigation of the Vasculature in Uppsala Seniors ( PIVUS ) Study?"
            ]
        },
        {
            "id": "task847-f0e327f774b94da6b348ffecf2bb7fa9",
            "input": "Children with residual brachial plexus birth palsy often develop internal rotation contractures with subsequent glenohumeral dysplasia seen on axial imaging. Coronal deformity (characterized by humeral head subluxation), and angular deformity (characterized by glenoid retroversion) have been defined. We hypothesize that the location of the biceps tendon characterizes rotational deformity.', 'A retrospective study was performed on 91 children (average age 3.2+/-2.2 y) who lacked external rotation beyond neutral and had magnetic resonance imaging (MRI) scans of bilateral shoulders performed at our institution between 2000 and 2007. The charts were reviewed for the measurement of the external rotation of the involved shoulder with the arm adducted and the scapula stabilized. The glenoscapular angle (glenoid version), the percentage of the humeral head anterior to the middle of the glenoid fossa (PHHA), and the angle of rotation of the biceps tendon (biceps angle) were measured on MRI scans of both shoulders. Statistical analysis was performed to compare these MRI measurements for the involved and uninvolved sides, and to identify the correlations between them and the external rotation.', 'The average biceps angle was 47.9+/-15.2 degrees on the uninvolved side and 26.2+/-15.0 degrees on the involved side. The average differences between the 2 shoulders in the biceps angle (21.7+/-20.5 degrees), the version (18.9+/-15.0 degrees), and the PHHA (19.8+/-13.6%) were all significant (P<0.001). Only the biceps angle correlated significantly with external rotation (P<0.001). This correlation remained significant even when the version and the PHHA were held constant (P=0.004).",
            "output": [
                "Do the biceps tendon as a measure of rotational deformity in residual brachial plexus birth palsy?"
            ]
        },
        {
            "id": "task847-f16cce063b43483cb9b40285a2465315",
            "input": "Caudal block is a common technique for paediatric analgesia but with the disadvantage of short duration of action after single injection. Caudal dexmedetomidine and clonidine could offer significant analgesic benefits. We compared the analgesic effects and side-effects of dexmedetomidine and clonidine added to bupivacaine in paediatric patients undergoing lower abdominal surgeries.', 'Sixty patients (6 months to 6 yr) were evenly and randomly assigned into three groups in a double-blinded manner. After sevoflurane in oxygen anaesthesia, each patient received a single caudal dose of bupivacaine 0.25% (1 ml kg(-1)) combined with either dexmedetomidine 2 microg kg(-1) in normal saline 1 ml, clonidine 2 microg kg(-1) in normal saline 1 ml, or corresponding volume of normal saline according to group assignment. Haemodynamic variables, end-tidal sevoflurane, and emergence time were monitored. Postoperative analgesia, use of analgesics, and side-effects were assessed during the first 24 h.', 'Addition of dexmedetomidine or clonidine to caudal bupivacaine significantly promoted analgesia time [median (95% confidence interval, CI): 16 (14-18) and 12 (3-21) h, respectively] than the use of bupivacaine alone [median (95% CI): 5 (4-6) h] with P<0.001. However, there was no statistically significant difference between dexmedetomidine and clonidine as regards the analgesia time (P=0.796). No significant difference was observed in incidence of haemodynamic changes or side-effects.",
            "output": [
                "Does addition of clonidine or dexmedetomidine to bupivacaine prolong caudal analgesia in children?"
            ]
        },
        {
            "id": "task847-93ee9a65dbd8408f894f85b480871f91",
            "input": "To assess the alterations in keratometric astigmatism following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy.', 'Sixteen consecutive patients were enrolled into the study. Conventional vitrectomy was applied to eight of the cases and 25-gauge transconjunctival sutureless vitrectomy was performed in eight patients. Keratometry was performed before and after the surgery.', 'In the 25-gauge transconjunctival sutureless pars plana vitrectomy group, statistically significant changes were not observed in the corneal curvature in any post-operative follow-up measurement (p > 0.05); whereas in the conventional pars plana vitrectomy group, statistically significant changes were observed in the first postoperative day (p = 0.01) and first postoperative month (p = 0.03). We noted that these changes returned to baseline in three months (p = 0.26).",
            "output": [
                "Do keratometric alterations following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy?"
            ]
        },
        {
            "id": "task847-b28366883bf64ad89ead76a7f752998b",
            "input": "LIM domain only 2 (LMO2) has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors. We investigate the involvement of LMO2 in pancreatic cancer.', 'We evaluated LMO2 expression in cultured cells, bulk tissues, and microdissected cells from pancreatic cancers by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry.', 'Of 164 pancreatic cancers, 98 (60%) were positive for LMO2 expression. LMO2 was more frequently detected in high-grade pancreatic intraepithelial neoplasia (PanIN) lesions (PanIN-2 and -3) than in low-grade PanIN lesions (PanIN-1A and -1B; P < .001) and was not detected in normal pancreatic ductal epithelium. The LMO2 messenger RNA levels were significantly higher in invasive ductal carcinoma cells than in normal pancreatic cells as evaluated by quantitative reverse transcription-polymerase chain reaction analyses of microdissected cells (P = .036). We also found higher incidence of LMO2 expression in histologic grade G1/G2 cancers than in grade G3 cancers (P < .001). The median survival time of LMO2-positive patients was significantly longer than that of LMO2-negative patients (P < .001), and multivariate analyses revealed that high LMO2 expression was an independent predictor of longer survival (risk ratio, 0.432, P < .001). Even among patients with a positive operative margin, LMO2-positive patients had a significant survival benefit compared with LMO2-negative patients. We further performed a large cohort study (n = 113) to examine the LMO2 messenger RNA levels in formalin-fixed paraffin-embedded samples and found similar results.",
            "output": [
                "Is lMO2 a novel predictive marker for a better prognosis in pancreatic cancer?"
            ]
        },
        {
            "id": "task847-2b941d1bf2f541d6997210eae7a092b4",
            "input": "Decisions involving risk often must be made under stressful circumstances. Research on behavioral and brain differences in stress responses suggest that stress might have different effects on risk taking in males and females.', 'In this study, participants played a computer game designed to measure risk taking (the Balloon Analogue Risk Task) fifteen minutes after completing a stress challenge or control task. Stress increased risk taking among men but decreased it among women.",
            "output": [
                "Does acute stress increase sex differences in risk seeking in the balloon analogue risk task?"
            ]
        },
        {
            "id": "task847-a87a06ddaa6d4aca8cc66f0389df377f",
            "input": "The left dorsolateral prefrontal cortex (DLPFC) is the most commonly used target for transcranial magnetic stimulation (TMS) in the treatment of depression. The \"5-cm rule\" is an empiric method used for probabilistic targeting of the DLPFC in most clinical trials. This rule may be suboptimal, as it does not account for differences in skull size or variations in prefrontal anatomy relative to motor cortex location. This study is a post hoc analysis of data from a large repetitive TMS (rTMS) trial in which we examined the variability of coil placement and how it affects antidepressant efficacy.', 'Fifty-four depressed subjects enrolled in a randomized, single-site trial received either active rTMS or sham for 3 weeks. Prior to treatment initiation, investigators placed vitamin E capsules at the point of stimulation and used a high-resolution magnetic resonance imaging (MRI) scan to image these fiducials relative to anatomy. We employed a semiautomated imaging-processing algorithm to localize the cortical region stimulated.', 'Active TMS significantly reduced Hamilton Depression Rating Scale (HDRS) scores. A linear model for this improvement involving the coordinates of the stimulated cortex location, age, and treatment condition was highly significant. Specifically, individuals with more anterior and lateral stimulation sites were more likely to respond.",
            "output": [
                "Is more lateral and anterior prefrontal coil location associated with better repetitive transcranial magnetic stimulation antidepressant response?"
            ]
        },
        {
            "id": "task847-547cf54e354e48619b919101434264e8",
            "input": "To study the expression of small ubiquitin-like modifier 1 (SUMO-1) in aseptic loosening of prosthesis implants and to investigate its role in regulating the susceptibility of prosthesis-loosening fibroblast-like synoviocytes (FLS) to Fas-induced apoptosis.', 'Specimens of aseptically loosened tissue were obtained at revision surgery, and the expression of SUMO-1 was analyzed by in situ hybridization. SUMO-1 levels in FLS were determined by quantitative polymerase chain reaction and Western blot analysis. Immunohistochemistry and confocal microscopy were used to study the subcellular localization of SUMO-1. The functional role of SUMO-1 in Fas-induced apoptosis of prosthesis-loosening FLS was investigated by small interfering RNA-mediated knockdown of SUMO-1 and by gene transfer of the nuclear SUMO-specific protease SENP1.', 'SUMO-1 was expressed strongly in aseptically loosened tissue and was found prominently at sites adjacent to bone. Prosthesis-loosening FLS expressed levels of SUMO-1 similar to the levels expressed by rheumatoid arthritis (RA) FLS, with SUMO-1 being found mainly in promyelocytic leukemia protein nuclear bodies. Knockdown of SUMO-1 had no effect on spontaneous apoptosis but significantly increased the susceptibility of prosthesis-loosening FLS to Fas-induced apoptosis. Gene transfer of the nuclear SUMO-specific protease SENP1 reverted the apoptosis-inhibiting effects of SUMO-1.",
            "output": [
                "Does small ubiquitin-like modifier 1 [ corrected ] mediate the resistance of prosthesis-loosening fibroblast-like synoviocytes against Fas-induced apoptosis?"
            ]
        },
        {
            "id": "task847-9a94c0566f454433baae49a41e439619",
            "input": "Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence.', 'We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects.', \"We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Beh\u00e7et's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7-15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4-25.8] and SIR 29.3 [95% CI 20.3-42.4] versus SIR 1.8 [95% CI 0.7-4.3], respectively). In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6-69.0] and OR 17.1 [95% CI 3.6-80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area.",
            "output": [
                "Is risk of tuberculosis higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy : The three-year prospective French Research Axed on Tolerance of Biotherapies registry?"
            ]
        },
        {
            "id": "task847-edf25b5aa5c24399ae5ff1add5d9c50d",
            "input": "Obesity protects against radiographic joint damage in rheumatoid arthritis (RA) through poorly defined mechanisms. Adipocytokines are produced in adipose tissue and modulate inflammatory responses and radiographic joint damage in animal models. The purpose of this study was to examine the hypothesis that adipocytokines modulate inflammation and radiographic joint damage in patients with RA.', 'We compared serum concentrations of leptin, resistin, adiponectin, and visfatin in 167 RA patients and 91 control subjects. The independent association between adipocytokines and body mass index (BMI), measures of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNFalpha]), and radiographic joint damage (Larsen score; n = 93 patients) was examined in RA patients by multivariable regression analysis first controlling for age, race, and sex, and then for obesity (BMI) and inflammation (TNFalpha, IL-6, and CRP).', 'Concentrations of all adipocytokines were significantly higher in RA patients than in controls; for visfatin and adiponectin, this association remained significant after adjusting for BMI, inflammation, or both. Visfatin concentrations were associated with higher Larsen scores, and this association remained significant after adjustment for age, race, sex, disease duration, BMI, and inflammation (odds ratio [OR] 2.38 [95% confidence interval (95% CI) 1.32-4.29], P = 0.004). Leptin concentrations showed a positive association with the BMI (rho = 0.58, P < 0.01) and showed a negative association with the Larsen score after adjustment for inflammation (OR 0.32 [95% CI 0.17-0.61], P < 0.001), but not after adjustment for BMI (OR 0.86 [95% CI 0.42-1.73], P = 0.67).",
            "output": [
                "Are adipocytokines associated with radiographic joint damage in rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-4cc836b89183463291ab159ebe48bc37",
            "input": "Interferon regulatory factor 5 is a transcription factor involved in type I interferon (IFN) secretion. This study was undertaken to investigate whether a 5-bp (CGGGG insertion/deletion) promoter polymorphism is involved in genetic predisposition to primary Sj\u00f6gren's syndrome (SS) and to assess the functional consequences of this polymorphism.\", 'The exploratory cohort consisted of 185 patients with primary SS and 157 healthy controls, and the replication cohort consisted of 200 patients with primary SS and 282 healthy controls. Levels of IRF5 messenger RNA (mRNA) were assessed at baseline and after in vitro infection with reovirus in peripheral blood mononuclear cells (PBMCs) from 30 patients with primary SS and from salivary gland epithelial cells that had been cultured for 4 weeks from patients with primary SS or sicca symptoms.', 'Carriage of the IRF5 4R CGGGG allele was associated with a greatly increased risk of primary SS in both cohorts (odds ratio 2.00 [95% confidence interval 1.5-2.7], P = 6.6 x 10(-6)). The CGGGG insertion/deletion polymorphism alone was sufficient to explain the association of primary SS with IRF5. The level of IRF5 mRNA in PBMCs depended significantly on genotype (P = 0.002) and was correlated with the levels of mRNA for the IFN-induced genes MX1 and IFITM1. Cultured salivary gland epithelial cells from patients carrying the 4R CGGGG IRF5 allele showed a high level of IRF5 mRNA (P = 0.04), which was amplified after reovirus infection (P = 0.026).",
            "output": [
                "Is the CGGGG insertion/deletion polymorphism of the IRF5 promoter a strong risk factor for primary Sj\u00f6gren 's syndrome?"
            ]
        },
        {
            "id": "task847-4a4f5c0ea8be462b9664311551078403",
            "input": "Treatment with oxaloacetate after traumatic brain injury has been shown to decrease blood glutamate levels and protect against the neurotoxic effects of glutamate on the brain. A number of potential mechanisms have been suggested to explain oxaloacetate-induced neuroprotection. We hypothesize that the primary mechanism by which intravenous oxaloacetate provides neuroprotection is by activation of the blood glutamate-scavenging enzyme glutamate-oxaloacetate transaminase, increasing thereby the driving force for the efflux of excess glutamate from brain interstitial fluids into blood. If so, coadministration of maleate, a glutamate-oxaloacetate transaminase-blocker is expected to prevent the neuroprotective effects of oxaloacetate.', 'A neurological severity score (NSS) was measured 1 hour after closed head injury (CHI) in rats. Then, rats received 30 microL/min/100 g infusion of saline, or 1 mmol/100 g solution of oxaloacetate, maleate, or a mixture of oxaloacetate and maleate. NSS was reassessed at 24 and 48 hour after CHI. Blood glutamate and glucose levels were measured at 0, 60, 90, and 120 minutes.', 'NSS improved significantly at 24 hour (P<0.001) and 48 hour (P<0.001) only in the rats treated with oxaloacetate. Blood glutamate decreased significantly in the oxaloacetate-treated group at 90 minute (at the conclusion of oxaloacetate administration) (P<0.00001), but not in the control, maleate or oxaloacetate+maleate groups. A strong correlation r2=0.86 was found to exist between the percent decrease in blood glutamate levels and percent improvement in NSS.",
            "output": [
                "Is the neuroprotective effects of oxaloacetate in closed head injury in rats mediated by its blood glutamate scavenging activity : evidence from the use of maleate?"
            ]
        },
        {
            "id": "task847-84a2dfb37f3a45cd901258a7ccc8e1fc",
            "input": "Injection drug users (IDUs) are at risk of acquiring HIV through injection and sexual practices.', 'We analyzed data collected in five U.S. cities between 2002 and 2004 to identify correlates of HIV infection among 3285 IDUs ages 15-30 years.', 'Overall, HIV prevalence was 2.8% (95% CI 2.3-3.4), ranging from 0.8% in Chicago to 6.3% in Los Angeles. Mean age was 24 years, 70% were male, 64% non-Hispanic (NH) white, 7% NH black, 17% Hispanic, and 12% were other/mixed race. HIV infection was independently associated with: race/ethnicity (NH black [AOR 4.1, 95% CI 1.9-9.1], Hispanic [AOR 3.6, 95% CI 1.5-8.4], or other/mixed [AOR 2.3, 95% CI 1.1-5.2] vs. NH white); males who only had sex with males compared to males who only had sex with females (AOR 15.3, 95% CI 6.8-34.5); injecting methamphetamine alone or with heroin compared to heroin only (AOR 4.0, 95% CI 1.7-9.7); reporting inconsistent means of obtaining income compared to regular jobs (AOR 2.3, 95% CI 1.1-4.8); and having a history of exchanging sex for money/drugs (AOR 2.8, 95% CI 1.5-5.2).",
            "output": [
                "Do young adult injection drug users in the United States continue to practice HIV risk behaviors?"
            ]
        },
        {
            "id": "task847-3600d218ca6043628ebb843d4e854538",
            "input": "We hypothesized that self-reported pad use per day (PPD) after pubovaginal sling (PVS) correlated with postoperative quality of life (QOL) scores.', 'Two hundred fifteen women completed the incontinence impact questionnaire 7 (IIQ-7) and urogenital distress inventory 6 (UDI-6) before PVS and during follow-up. Starting 3 days before a visit, women recorded the number of protective urinary pad changes per day. Analysis of variance and Pearson correlation tests were used to determine if women reporting zero, one, or greater than or equal to two urinary pads per day after PVS had significantly different changes in baseline QOL scores.', 'Over a mean 8.5 months follow-up after PVS, 131, 56, and 28 women reported zero, one, and greater than or equal to two pad changes/day. Each pad group showed progressively less improvement from baseline IIQ-7 and UDI-6 scores after PVS. Change in IIQ-7 and UDI-6 scores negatively correlated with PPD (p < 0.0001).",
            "output": [
                "Does self-reported pad use per day reflect patient quality of life after pubovaginal sling surgery?"
            ]
        },
        {
            "id": "task847-dad2bd1cdea4478d9dc60e379406b98d",
            "input": "The Ras-association family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-association (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1-10 in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples.', \"COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst RASSF10 was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC).",
            "output": [
                "Are the novel RASSF6 and RASSF10 candidate tumour suppressor genes frequently epigenetically inactivated in childhood leukaemias?"
            ]
        },
        {
            "id": "task847-95fd1a17138140e5af43a1e8e221e5c8",
            "input": "Because of greater recognition and improved imaging capabilities, intraductal papillary mucinous neoplasms (IPMNs) are being diagnosed with increasing frequency. IPMNs of the main pancreatic duct cause symptoms and lead to pancreatitis. Side-branch (SB) IPMNs are thought to cause symptoms less frequently, and their association with pancreatitis is not well defined.', 'Our purpose was to ascertain whether an association exists between SB-IPMN and pancreatitis.', 'Single-center, retrospective study.', 'Academic medical center.', 'A total of 305 patients underwent EUS examinations between October 2002 and October 2006 for pancreatic cystic lesions.', 'The main outcome measure was the frequency of acute or chronic pancreatitis that was not procedurally related.', 'Thirty-two patients had SB-IPMNs, and 11 (34%) had pancreatitis. Three patients reported a single episode, and 8 patients reported having recurrent episodes of pancreatitis. Overall, 17 (53%) patients had symptoms possibly attributable to SB-IPMN. Female sex (73% vs 38%) and multiple pancreatic lesions (54% vs 24%) were more commonly seen in those with pancreatitis, but were not statistically significant factors. Larger cyst size or cyst fluid marker levels did not appear associated with pancreatitis occurrence. EUS-FNA demonstrated communication with the pancreatic duct in 94% and thick, mucinous fluid in 84%.",
            "output": [
                "Is pancreatitis frequent among patients with side-branch intraductal papillary mucinous neoplasia diagnosed by EUS?"
            ]
        },
        {
            "id": "task847-5bff4013c5d747968207c088944eaafc",
            "input": "Previous results have shown that mice lacking in the group 1B phospholipase A(2) (Pla2g1b) are resistant to obesity and diabetes induced by feeding a diabetogenic high-fat/high-carbohydrate diet. This study examined the potential of using the Pla2g1b inhibitor methyl indoxam as therapy to suppress diet-induced obesity and diabetes.', 'Male C57BL/6 mice were fed the diabetogenic diet with or without methyl indoxam supplementation. Body weight gain, fasting plasma glucose levels, glucose tolerance and postprandial lysophospholipid absorption were compared.', 'Wild-type C57BL/6 mice fed the diabetogenic diet without Pla2g1b inhibitor showed 31 and 69% body weight gain after 4 and 10 weeks respectively. These animals also showed elevated plasma glucose levels and were glucose intolerant. In contrast, C57BL/6 mice fed the diabetogenic diet with 90 mg.kg(-1) of methyl indoxam gained only 5% body weight after 10 weeks. These animals were also euglycaemic and displayed normal glucose excursion rates in glucose tolerance test. Methyl indoxam suppression of diet-induced body weight gain and glucose intolerance was correlated with the inhibition of Pla2g1b-mediated postprandial lysophospholipid absorption.",
            "output": [
                "Does the phospholipase A ( 2 ) inhibitor methyl indoxam suppress diet-induced obesity and glucose intolerance in mice?"
            ]
        },
        {
            "id": "task847-5ed5573740814a1fac016fde0098ad59",
            "input": "Skeletal muscle is an important target tissue for thyroid hormone (TH). It is currently unknown which genes are regulated by physiological TH levels.', 'We examined the effects of l-thyroxine on human skeletal muscle transcriptome.', 'Microarray analysis of transcript levels was performed using skeletal muscle biopsies from patients under euthyroid and hypothyroid conditions.', 'The study was conducted in a university hospital laboratory.', 'We studied skeletal muscle obtained from 10 thyroidectomized patients with differentiated thyroid carcinoma on and after 4 wk off L-thyroxine replacement.', 'Gene expression changes were measured using microarrays. Results were analyzed using dedicated statistical methods.', 'We detected 607 differentially expressed genes on L-thyroxine treatment, of which approximately 60% were positively and approximately 40% were negatively regulated. Representative genes were validated by quantitative PCR. Genes involved in energy and fuel metabolism were overrepresented among the up-regulated genes, of which a large number were newly associated with thyroid state. L-thyroxine therapy induced a large down-regulation of the primary transcripts of the noncoding microRNA pair miR-206/miR-133b.",
            "output": [
                "Do physiological thyroid hormone levels regulate numerous skeletal muscle transcripts?"
            ]
        },
        {
            "id": "task847-a5454436514a41a296050028d3b6984d",
            "input": "To compare walking characteristics of individuals with Parkinson's disease (PD) using a new walking aid, the WalkAbout, with usual walking.\", 'Fifteen subjects with PD were recruited. Subjects walked in their usual fashion and then walked again in the WalkAbout. Gait parameters, 5-min walk, and oxygen consumption were recorded.', 'Stride lengths were shorter when using the WalkAbout. On an average, the distance walked in 5 min and the oxygen uptake was not different when walking with the WalkAbout compared with the usual walk. Eight subjects (responders) walked further with the WalkAbout compared to their usual walk (164.90 +/- 55.72 m vs. 140.82 +/- 55.94 m). Seven subjects (non-responders) walked a shorter distance while using the WalkAbout compared to their usual walk (241.79 +/- 73.06 m vs. 281.24 +/- 82.83 m). Compared to non-responders, responders were older, had more severe disability, and were more likely to use an assistive device for walking. Responders walked more slowly, had a shorter stride length, and walked shorter distances in 5 min than non-responders.",
            "output": [
                "Does evaluation of a new device to prevent fall in persons with Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-c552d65a8e054bde801bf41fdbb89092",
            "input": "Determine the effect that increased medical surgical (med/surg) bed occupancy has on the time interval from admission order to arrival in the bed for the patients admitted from the emergency department (ED).', \"This retrospective observational study compares the total hospital bed occupancy rate and the medical surgical inpatient bed occupancy rate to daily averages for the time interval from admission order (patient posting for admission) to the patient's arrival in the inpatient bed. Medical surgical inpatient bed occupancy of 92% was chosen because beyond that rate we observed more frequent extended daily transfer times. The data is from a single large tertiary care institute with 590 beds and an annual ED census of 80,000.\", 'Group 1 includes 38 days with (med/surg) inpatient bed occupancy rate of less than 92%, with an average ED daily wait of 2.5 hrs (95% confidence interval 2.23-2.96) for transfer from the ED to the appropriate hospital bed. Group 2 includes 68 days with med/surg census greater than 92% with an average ED daily wait of 4.1 hours (95% confidence interval 3.7-4.5). Minimum daily average for the two groups was 1.2 hrs and 1.3 hrs, respectively. The maximum average was 5.6 hrs for group 1 and 8.6 hrs for group 2. Comparison of group 1 to 2 for wait time to hospital bed yielded p <0.01. Total reported hospital occupied capacity shows a correlation coefficient of 0.16 to transfer time interval, which indicates a weak relationship between total occupancy and transfer time into the hospital. Med/surg occupancy, the beds typically used by ED patients, has a 0.62 correlation coefficient for a moderately strong relationship.",
            "output": [
                "Does higher inpatient medical surgical bed occupancy extend admitted patients ' stay?"
            ]
        },
        {
            "id": "task847-5562fe2440d64c3f8c443d2a472a3818",
            "input": "This is a prospective study of psychiatric patients presenting to the emergency department (ED) to determine the value of routine laboratory studies used to attempt to exclude concomitant medical illness.', 'Physical exams and laboratory tests were performed on 375 psychiatric patients presenting for \"medical clearance\" in the ED. Upon completion of these tests, the percentage and impact of abnormal physical exams and laboratory results were assessed.', 'Fifty-six of 375 patients (14.9%) had a non-substance-induced laboratory abnormality. Forty-two of these 56 patients (75.0%) also had abnormal history or physical exam findings indicating laboratory screening. Ten had normal history and physical exams with insignificant laboratory abnormalities. The four (1.1% [95% CI 0.3-2.7%]) remaining patients with normal history and physical exams had abnormal urinalyses which did not affect final disposition or contribute to altered behavior.",
            "output": [
                "Is routine laboratory testing to evaluate for medical illness in psychiatric patients in the emergency department largely unrevealing?"
            ]
        },
        {
            "id": "task847-1c13f8f2c3b44e8d80d62417790f2d28",
            "input": "Vascular endothelial growth factor (VEGF) has been well documented to stimulate cell proliferation and differentiation; however, we have observed that copper (Cu)-induced regression of heart hypertrophy was VEGF-dependent. The present study was undertaken to test the hypothesis that Cu causes alterations in the distribution of VEGF receptors (VEGFRs) in hypertrophic cardiomyocytes so that it switches the signalling pathway from stimulation of cell growth to reversal of cell hypertrophy.', 'Primary cultures of neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final concentration of 100 microM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cardiomyocytes were exposed to copper sulfate at a final concentration of 5 microM in cultures for 24 h with a concomitant presence of PE. Flow cytometry, gene silencing, and ELISA procedures were used to analyse the changes in VEGFRs and their relationship with regression of cardiomyocyte hypertrophy. Cu did not change the concentration of VEGF in culture media, but increased the ratio of VEGFR-1 to VEGFR-2 two-fold. Gene silencing of VEGFR-2, in the absence of Cu addition, reversed PE-induced cardiomyocyte hypertrophy, which was suppressed by an anti-VEGF antibody. Gene silencing of VEGFR-1 blocked Cu-induced regression of cell hypertrophy and decreased the activity of cGMP-dependent protein kinase-1 (PKG-1). A PKG-1 antagonist, Rp-8-pCPT-cGMPS, blocked both Cu- and VEGFR-2 gene silencing-induced regression of cardiomyocyte hypertrophy.",
            "output": [
                "Is copper-induced regression of cardiomyocyte hypertrophy associated with enhanced vascular endothelial growth factor receptor-1 signalling pathway?"
            ]
        },
        {
            "id": "task847-71c2674099324e1a9a802561cab5474a",
            "input": "Myocardial electrical impedance (MEI) has shown to be an effective indicator of myocardial ischemia. We have previously developed a novel monitor for measuring MEI in near-real time. The object of this study was to test whether drug-induced changes in the frequency of the periodic myocardial electrical activity, as measured by the heart rate (HR), affect MEI measurements made with our monitor.', 'Thirty dogs were randomly assigned to one of three study groups (placebo, isoproterenol or esmolol) and then anesthetized with sodium thiamylal, intubated, ventilated, given isoflurane, and had venous, arterial, and pulmonary artery catheters placed. Median sternotomy was performed to facilitate myocardial exposure and to allow the left anterior descending (LAD) coronary artery to be isolated. Following baseline measurements, saline (control), isoproterenol or esmolol was administered and the LAD coronary artery was occluded in a timed sequence in order to study the effects of heart rate changes and demonstrate induced myocardial ischemia on MEI.', 'Isoproterenol raised the HR and esmolol lowered the HR without affecting our MEI measurements. Myocardial electrical impedance increased during LAD coronary artery occlusion in all groups, as previously shown.",
            "output": [
                "Does myocardial electrical activity affect myocardial electrical impedance measurements?"
            ]
        },
        {
            "id": "task847-7c1d1a3d58c847989ae0ad3dd9a45cfa",
            "input": "To compare ambulatory blood pressure (ABP) in nonoverweight, prepubertal children with and without primary snoring (PS), and to investigate whether PS is a part of the dose-response relationship between sleep-disordered breathing (SDB) and BP in children.', 'This was a cross-sectional community-based study involving 190 children age 6 to 13 years. Each participant underwent an overnight sleep study and ABP monitoring after completing a validated sleep symptoms questionnaire. Individual systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial BP were calculated for wake and sleep periods. Subjects were hypertensive if mean SBP or DBP was > 95th percentile (relative to sex and height) of reference.', 'A total of 56 nonsnoring controls, 46 children with PS, 62 children with an apnea-hypopnea index (AHI) of 1 to 3, and 26 children with an AHI > 3 were identified. The daytime and nighttime BP increased across the severity spectrum of SDB. The dose-response trends for the proportion of subjects with nighttime systolic and diastolic hypertension also were significant. Nighttime DBP was significantly higher in the children with PS compared with controls after adjusting for age, sex, and body mass index.",
            "output": [
                "Is blood pressure elevated in children with primary snoring?"
            ]
        },
        {
            "id": "task847-ce1222507d0e4a7eba675ee6a706a541",
            "input": "We examined the effect of male circumcision on the acquisition of 3 nonulcerative sexually transmitted infections (STIs).', 'We evaluated the incidence of STI among men aged 18-24 years enrolled in a randomized trial of circumcision to prevent human immunodeficiency virus (HIV) infection in Kisumu, Kenya. The outcome was first incident nonulcerative STI during 2 years of follow-up. STIs examined were laboratory-detected Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis infection.', 'There were 342 incident infections among 2655 men followed up. The incidences of infection due to N. gonorrhoeae, C. trachomatis, and T. vaginalis were 3.48, 4.55, and 1.32 cases per 100 person-years, respectively. The combined incidence of N. gonorrhoeae and C. trachomatis infection was 7.26 cases per 100 person-years (95% confidence interval, 6.49-8.13 cases per 100 person-years). The incidences of these STIs, individually or combined, did not differ by circumcision status as a time-dependent variable or a fixed variable based on assignment. Risks for incident STIs in multivariate analysis included an STI at enrollment, multiple sex partners within <30 days, and sexual intercourse during menses in the previous 6 months; condom use was protective.",
            "output": [
                "Does adult male circumcision reduce the risk of incident Neisseria gonorrhoeae , Chlamydia trachomatis , or Trichomonas vaginalis infection : results from a randomized , controlled trial in Kenya?"
            ]
        },
        {
            "id": "task847-44ab34edad5245ff8a8650c16fdf9b20",
            "input": "To increase the supply, many countries harvest allograft valves from explanted hearts of transplant recipients with ischaemic (ICM) or dilated cardiomyopathy (DCM). This study determines the structural integrity of valves from cardiomyopathic hearts.', 'Extracellular matrix (ECM) was examined in human valves obtained from normal, ICM, and DCM hearts. To confirm if ECM changes were directly related to the cardiomyopathy, we developed a porcine model of chronic ICM. Histology and immunohistostaining, as well as non-invasive multiphoton and second harmonic generation (SHG) imaging revealed marked disruption of ECM structures in human valves from ICM and DCM hearts. The ECM was unaffected in valves from normal and acute ICM pigs, whereas chronic ICM specimens showed ECM alterations similar to those seen in ICM and DCM patients. Proteins and proteinases implicated in ECM remodelling, including Tenascin C, TGFbeta1, Cathepsin B, MMP2, were upregulated in human ICM and DCM, and porcine chronic ICM specimens.",
            "output": [
                "Is cardiomyopathy associated with structural remodelling of heart valve extracellular matrix?"
            ]
        },
        {
            "id": "task847-73068e0ef2be4ef4b405e9a76d0fbf64",
            "input": "The regulation of strong emotions has important implications for health, particularly among individuals with chronic illness. We focus this brief review on effective psychosocial interventions that emphasize and teach skills to improve emotion regulation in the context of health-related outcomes.', 'Recent work in the area of emotion-regulation interventions has tested the effects of emotion-regulation family therapy, group-based emotion-regulation psychotherapy, expressive writing, and school-based prevention programs. Emotion-regulation psychotherapy for families shows some benefits for both patients and their family members. Group emotion-regulation interventions and expressive writing result in physical and psychosocial improvement for patients with medical or psychiatric illness. School-based programs show improved emotion knowledge, emotion regulation, and emotional competence, relative to standard academic curricula and existing prevention programs.",
            "output": [
                "Does recent evidence support emotion-regulation interventions for improving health in at-risk and clinical populations?"
            ]
        },
        {
            "id": "task847-c4a887c86f98406b978ea8c29f4970fb",
            "input": "Microsporogenesis in monocots is often characterized by successive cytokinesis with centrifugal cell plate formation. Pollen grains in monocots are predominantly monosulcate, but variation occurs, including the lack of apertures. The aperture pattern can be determined by microsporogenesis features such as the tetrad shape and the last sites of callose deposition among the microspores. Potamogeton belongs to the early divergent Potamogetonaceae and possesses inaperturate pollen, a type of pollen for which it has been suggested that there is a release of the constraint on tetrad shape. This study aimed to investigate the microsporogenesis and the ultrastructure of pollen wall in species of Potamogeton in order to better understand the relationship between microsporogenesis features and the inaperturate condition.', 'The microsporogenesis was investigated using both light and epifluorescence microscopy. The ultrastructure of the pollen grain was studied using transmission electron microscopy.', 'The cytokinesis is successive and formation of the intersporal callose wall is achieved by centrifugal cell plates, as a one-step process. The microspore tetrads were tetragonal, decussate, T-shaped and linear, except in P. pusillus, which showed less variation. This species also showed a callose ring in the microsporocyte, and some rhomboidal tetrads. In the mature pollen, the thickening observed in a broad area of the intine was here interpreted as an artefact.",
            "output": [
                "Is release of developmental constraints on tetrad shape confirmed in inaperturate pollen of Potamogeton?"
            ]
        },
        {
            "id": "task847-c3f379223187486d9a2e47702d5d574b",
            "input": "Lactate dehydrogenase-elevating virus (LDV) is a natural infectious agent of mice. Like several other viruses, LDV causes widespread and very rapid but transient activation of both B cells and T cells in lymphoid tissues and the blood. The mechanism of this activation has not been fully described and is the focus of the current studies.', \"A known inducer of early lymphocyte activation is IFNalpha, a cytokine strongly induced by LDV infection. Neutralization of IFNalpha in the plasma from infected mice ablated its ability to activate lymphocytes in vitro. Since the primary source of virus-induced IFNalpha in vivo is often plasmacytoid dendritic cells (pDC's), we depleted these cells prior to LDV infection and tested for lymphocyte activation. Depletion of pDC's in vivo eradicated both the LDV-induced IFNalpha response and lymphocyte activation. A primary receptor in pDC's for single stranded RNA viruses such as LDV is the toll-like receptor 7 (TLR7) pattern recognition receptor. Infection of TLR7-knockout mice revealed that both the IFNalpha response and lymphocyte activation were dependent on TLR7 signaling in vivo. Interestingly, virus levels in both TLR7 knockout mice and pDC-depleted mice were indistinguishable from controls indicating that LDV is largely resistant to the systemic IFNalpha response.",
            "output": [
                "Does lactate dehydrogenase-elevating virus induce systemic lymphocyte activation via TLR7-dependent IFNalpha responses by plasmacytoid dendritic cells?"
            ]
        },
        {
            "id": "task847-659bf92a3df444c4972583d991e20e68",
            "input": "Yes-associated protein (YAP), a downstream target of the Hippo signaling pathway, was recently linked to hepatocarcinogenesis in a mouse hepatocellular carcinoma (HCC) model. The objective of the current study was to investigate the clinical significance of YAP in HCC and its prognostic values in predicting survival and tumor recurrence.', 'The authors collected 177 pairs of tumor and adjacent nontumor tissue from HCC patients with definitive clinicopathologic and follow-up data. YAP expression was determined by immunohistochemistry, Western blot analysis, and quantitative polymerase chain reaction. Association of YAP with each clinicopathologic feature was analyzed by Pearson chi-square test, and HCC-specific disease-free survival and overall survival by Kaplan-Meier curves and log-rank test. Multivariate Cox regression analyses of YAP in HCC were also performed.', 'YAP was expressed in the majority of HCC cases (approximately 62%) and mainly accumulated in the tumor nucleus. Overexpression of YAP in HCC was significantly associated with poorer tumor differentiation (Edmonson grade; P = .021) and high serum alpha-fetoprotein (AFP) level (P < .001). Kaplan-Meier and Cox regression data indicated that YAP was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.653; 95% confidence interval [95% CI], 1.081-2.528 [P = .02]) and overall survival (HR, 2.148; 95% CI, 1.255-3.677 [P = .005]).",
            "output": [
                "Is yes-associated protein an independent prognostic marker in hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-1b2816b2e75845d8b27996ae8674438f",
            "input": "The Australasian Triage Scale is a simple five-point system of triage that forms the basis of triage in most emergency departments in Australia. The Manchester Triage System (MTS) is an algorithmic aid to the process of triage. It utilises a series of flow charts that lead the triage nurse to a logical choice of triage category also using a five-point scale.', 'To evaluate the inter-rater reliability of the MTS in an Australian emergency department.', '50 triage scenarios were derived from the notes of 50 consecutive patients who had presented to the emergency department. All available nurses who had been trained to use the MTS were invited to participate in the study. The nurses were asked to assign a triage category to each scenario using the MTS. Weighted kappas were calculated for all pairs of raters.', '20 nurses participated in the study. The range of kappas was 0.4007 to 0.8018, with a median of 0.6304.",
            "output": [
                "Does the Manchester Triage System provide good reliability in an Australian emergency department?"
            ]
        },
        {
            "id": "task847-4145ea2cf8af4ad9a3d522fa52b01975",
            "input": "Elevated levels of B-type natriuretic peptide (BNP) are associated with adverse clinical outcomes in acute coronary syndrome (ACS), but several questions remain outstanding. Firstly, it has not yet been determined whether an additional BNP sample at 7 weeks post ACS would enhance risk prediction. Secondly, we assessed whether the prognostic potential of BNP in ACS could be explained by echocardiographic abnormalities such as left ventricular hypertrophy (LVH).', 'We measured bedside BNP levels in 443 consecutive patients presenting with ACS and at 7 weeks outpatient follow-up. Main outcome measure was either all-cause mortality, readmission with ACS, or congestive heart failure) at 10 months from presentation.', 'Of the 443 patients, 120 patients presented with ST-elevation myocardial infarction (27%). There were 90 cardiovascular (CV) events at 10 months. Adjusting for age, sex, hypertension, diabetes mellitus, smoking status, renal dysfunction, left ventricular ejection fraction, and echocardiographic LVH elevated near patient BNP levels (>80 pg/mL) were still associated with subsequent CV events when measured on admission (adjusted relative risk [RR] 2.63 [95% CI 1.34-5.19)] and also at 7 weeks post ACS (adjusted RR 4.12 [95% CI 1.58-10.72]). Patients with persistent BNP elevation at 7 weeks were also at an increased risk of CV events compared to those with an initial high BNP which then fell (unadjusted RR 4.04 [95% CI 1.24-13.15]).",
            "output": [
                "Does serial bedside B-type natriuretic peptide strongly predict prognosis in acute coronary syndrome independent of echocardiographic abnormalities?"
            ]
        },
        {
            "id": "task847-0ca6123730dd47e49d18eecc7ca558ef",
            "input": "To characterize the human ovarian xenograft revascularization process.', 'Prospective experimental study.', 'Gynecology research unit in a university hospital.', 'Ovarian biopsies were obtained from 12 women aged 22-35 years.', 'Frozen-thawed human ovarian fragments were intraperitoneally grafted into nude mice.', 'Graft perfusion was evaluated by Hoechst 33342 uptake. Murine and human vascularization was analyzed by CD31 and von Willebrand factor double immunostaining.', 'On day 3, some murine neovessels and perfused areas were located at the periphery of the fragments. Nonperfused native human vessels were present in the fragments. From day 5, perfused areas and murine endothelial areas progressively increased. Host angiogenesis initiated ovarian graft reperfusion: murine neovessels penetrated from the periphery and were colocalized with perfused areas. By day 10, the increase in perfusion and murine vascularization was significant. The center of the fragments was perfused and a significant increase was observed in human vasculature.",
            "output": [
                "Do both host and graft vessels contribute to revascularization of xenografted human ovarian tissue in a murine model?"
            ]
        },
        {
            "id": "task847-1c341c420da3447e915fd5b62a2ad729",
            "input": "Both obesity and type 2 diabetes are among the risk factors for breast cancer development. Combined effect of these metabolic abnormalities on breast cancer risk however, has not been examined in premenopausal women. We tested this association in type 2 diabetic women, categorized as obese, overweight and normal body weight groups based on BMI.', 'A total of 101 subjects were included in this study. Serum levels of IL-6, TNF-alpha, C reactive protein, leptin, TGF-alpha, adiponectin and insulin were measured by ELISA. Data were logarithmically transformed for variables not normally distributed. Analysis of variance with post-hoc Bonferroni was applied to compare the data between the groups. Simple and partial correlation coefficients between the variables were determined and a stepwise multiple linear regression analysis was performed to determine the relationships between the variables of interest.', 'Significantly increased levels of IL-6, C reactive protein, leptin and significantly decreased levels of adiponectin were found in obese group, while the levels of TNF-alpha and TGF-alpha were unaltered. A positive correlation between waist circumference and IL-6 was found in obese group. Similarly, C reactive protein, waist and hip circumferences were linearly correlated with BMI in obese group. Stepwise multiple linear regression analysis revealed several significant predictors for breast cancer risk.",
            "output": [
                "Do combined effects of obesity and type 2 diabetes contribute to increased breast cancer risk in premenopausal women?"
            ]
        },
        {
            "id": "task847-ef458fb8ccc34f4bac911788ad96f276",
            "input": "The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma (DLBCL) remains to be defined. We aimed to compare CHOP plus rituximab (R-CHOP) with CHOP alone and determine the value of radiotherapy in these patients.', 'Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study.', 'Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response (CR) rate was 77% both in R-CHOP and CHOP groups (P=0.945). After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival (PFS) (76% vs. 85%; log-rank P=0.215) and 5-year overall survival (OS) (90% vs. 96%; log-rank P=0.175) compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone (86% vs. 71%; log-rank P=0.005). At multivariate analysis, patients who had CR (P=0.008) and received radiotherapy (P=0.003) were significantly associated with superior PFS.",
            "output": [
                "Is addition of rituximab associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma?"
            ]
        },
        {
            "id": "task847-c1d1b06da3cf4063ba915c4492c6a24f",
            "input": "Whether low socioeconomic status (SES) is associated with worse rheumatoid arthritis (RA) outcomes in countries with general tax-financed healthcare systems (such as Sweden) remains to be elucidated. Our aim was to investigate the influence of educational background (achieving university/college degree (high) or not (low)) on the outcomes of early RA, in terms of disease activity (DAS28), pain (VAS-pain), and functional impairment (HAQ).', 'We evaluated DMARD-na\u00efve RA patients recruited in the Epidemiological Investigation of RA (EIRA) study with outcomes followed in the Swedish Rheumatology Quality (SRQ) register (N\\u2009=\\u20093021). Outcomes were categorized in three ways: (1) scores equal to/above median vs. below median; (2) DAS28-based low disease activity, good response, remission; (3) scores decreased over the median vs. less than median. Associations between educational background and outcomes were calculated by modified Poisson regressions, at diagnosis and at each of the three standard (3, 6, 12 months) follow-up visits.', 'Patients with different educational background had similar symptom durations (195 days) and anti-rheumatic therapies at baseline, and comparable treatment patterns during follow-up. Patients with a high education level had significantly less pain and less functional disability at baseline and throughout the whole follow-up period (VAS-pain: baseline: 49 (28-67) vs. 53 (33-71), p\\u2009<0.0001; 1-year visit: RR\\u2009=\\u20090.81 (95% CI 0.73-0.90). HAQ: baseline: 0.88 (0.50-1.38) vs. 1.00 (0.63-1.50), p\\u2009=\\u20090.001; 1-year visit: 0.84 (0.77-0.92)). They also had greater chances to achieve pain remission (VAS-pain\\u2009\u226420) after one year (1.17 (1.07-1.28)). Adjustments for smoking and BMI altered the results only marginally. Educational background did not influence DAS28-based outcomes.",
            "output": [
                "Is higher education associated with a better rheumatoid arthritis outcome concerning for pain and function but not disease activity : results from the EIRA cohort and Swedish rheumatology register?"
            ]
        },
        {
            "id": "task847-6c5d3110f90e4c3eb124c85cb9f21900",
            "input": "The aim of this study is to investigate whether (-)-epigallocatechin-3-gallate (EGCG) can prevent the UA-induced inflammatory effect of human umbilical vein endothelial cells (HUVEC) and the involved mechanisms in vitro.', 'HUVEC were subjected to uric acid (UA) with or without EGCG treatment. RT-PCR and western blots were performed to determine the level of inflammation marker. The antioxidant activity was evaluated by measuring scavenged reactive oxygen species (ROS). Functional studies of the role of Notch-1 in HUVEC lines were performed using RNA interference analyses.', 'UA significantly increased the expressions of IL-6, ICAM-1, TNF-\u03b1, and MCP-1 and the production of ROS in HUVEC. Meanwhile, the expression of Notch-1 and its downstream effects significantly increased. Using siRNA, inhibition of Notch-1 signaling significantly impeded the expressions of inflammatory cytokines under UA treatment. Interestingly, EGCG suppressed the expressions of inflammatory cytokines and the generation of ROS. Western blot analysis of Notch-1 showed that EGCG significantly decreased the expressions of inflammatory cytokines through Notch-1 signaling pathways.",
            "output": [
                "Does eGCG attenuate Uric Acid-Induced Inflammatory and Oxidative Stress Responses by Medicating the NOTCH Pathway?"
            ]
        },
        {
            "id": "task847-2c4c87d0e51141f895137d1dd818280b",
            "input": "Epigenetic aberrations play a central role in the pathophysiology of acute myeloid leukemia (AML). It has been shown that molecular signatures based on DNA-methylation (DNAm) patterns can be used for classification of the disease. In this study, we followed the hypothesis that DNAm at a single CpG site might support risk stratification in AML.', 'Using DNAm profiles of 194 patients from The Cancer Genome Atlas (TCGA), we identified a CpG site in complement component 1 subcomponent R (C1R) as best suited biomarker: patients with higher methylation at this CpG site (>27\\xa0% DNAm) reveal significantly longer overall survival (53 versus 11\\xa0months; P\\u2009<\\u20090.0001). This finding was validated in an independent set of 62 DNAm profiles of cytogenetically normal AML patients (P\\u2009=\\u20090.009) and with a region-specific pyrosequencing assay in 84 AML samples (P\\u2009=\\u20090.012). DNAm of C1R correlated with genomic DNAm and gene expression patterns, whereas there was only moderate association with gene expression levels of C1R. These results indicate that DNAm of C1R is a biomarker reflecting chromatin reorganization rather than being of pathophysiological relevance per se. Notably, DNAm of C1R was associated with occurrence of specific genomic mutations that are traditionally used for risk stratification in AML. Furthermore, DNAm of C1R correlates also with overall survival in several other types of cancer, but the prognostic relevance was less pronounced than in AML.",
            "output": [
                "Is dNA-methylation in C1R a prognostic biomarker for acute myeloid leukemia?"
            ]
        },
        {
            "id": "task847-85061fc14a2b4521b39bfd68b28145f9",
            "input": "The aims of the present study were to explore pre-treatment predictors of weight loss during radiation treatment only in head and neck cancer (HNSCC) patients and investigate the weight loss in patients with or without a feeding tube.', 'Retrospectively, weight change during curative radiotherapy was investigated in 476 consecutive HNSCC patients. Independent predictors were identified using multivariate regression analysis with weight loss below or above 5 % as the primary dependent variable.', 'Baseline BMI, tumor site, and stage predicted weight loss above 5 %. The odds of weight loss above 5 % in patients with BMI >25 were 3.00\\u2009\u00b1\\u20090.64 times higher compared with patients with BMI <25 (p\\u2009<\\u20090.0001). Patients with pharyngeal, oral cavity, or supraglottic tumors had 3.12\\u2009\u00b1\\u20090.80 times higher odds of weight loss above 5 % compared with glottic cancer patients (p\\u2009<\\u20090.0001), and the odds were 1.68\\u2009\u00b1\\u20090.40 times higher in stage III-IV patients compared with stage I-II patients (p\\u2009=\\u20090.03). Seperate analyses revealed that tumor site and stage only predicted weight loss in patients with BMI >25 but not in patients with BMI <25. Patients receiving a feeding tube weighed less than patients without (73.8 vs 78.3 kg) and feeding tube reduced, but did not prevent, weight loss which averaged 6.7\\u2009\u00b1\\u20094.7 kg (7.4\\u2009\u00b1\\u20094.7 %) compared with 4.7\\u2009\u00b1\\u20095.9 kg (5.5\\u2009\u00b1\\u20096.0 %) in patients without a feeding tube (P\\u2009<\\u20090.0001).",
            "output": [
                "Is prediction of critical weight loss during radiation treatment in head and neck cancer patients dependent on BMI?"
            ]
        },
        {
            "id": "task847-9c8cb4c5fa6c4ecd927e4e2116a85325",
            "input": "Phosphatase of regenerating liver-3 (PRL-3) has been implicated in controlling cancer cell invasiveness. Deregulated expression of PRL-3 is involved in cancer progression and predicts poor overall survival. Recent studies have revealed critical roles for microRNAs in various cellular processes, including tumorigenic development. In this study, we aimed to explore the linkage between PRL-3 and microRNAs in gastric cancer. We found that PRL-3 transcript levels were positively correlated with miR-210 levels in gastric cancer tissues. In gastric cancer cells, PRL-3 upregulated miR-210 expression in a HIF-1\u03b1-dependent fashion under normoxia and hypoxia. In addition, PRL-3 activated NF-\u03baB signaling and promoted HIF-1\u03b1 expression through modulating phosphorylation of p65. NF-\u03baB signaling, HIF-1\u03b1, and miR-210 partially contributed to PRL-3-induced migration and invasion. Furthermore, the levels of PRL-3, HIF-1\u03b1, and miR-210 transcripts inversely affected the overall survival of gastric cancer patients. Our work identified the existence of a PRL-3-NF-\u03baB-HIF-1\u03b1-miR-210 axis, thus providing new insight into the role of PRL-3 in promoting gastric cancer invasiveness.",
            "output": [
                "Does pRL-3 promote gastric cancer migration and invasion through a NF-\u03baB-HIF-1\u03b1-miR-210 axis?"
            ]
        },
        {
            "id": "task847-51ca3f9966f44ecabdde326b0424062f",
            "input": "Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS.', 'A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had P<5\u00d710(-6) in the genome-wide association studies meta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies P=5.33\u00d710(-5)). The mRNA expression levels of RUNX2 were upregulated in calcified valves and associated with eQTL-SNPs. CACNA1C encoding a subunit of a voltage-dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in CACNA1C was associated with higher expression of the gene.",
            "output": [
                "Do calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease?"
            ]
        },
        {
            "id": "task847-ffcc76fbb7ea4bf1aeec2febcace062f",
            "input": "The main pathophysiology of abdominal aortic aneurysm (AAA) considerably overlaps with that of atherosclerosis. We reported that incretins [glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP)] or a dipeptidyl peptidase-4 inhibitor (DPP-4I) suppressed atherosclerosis in apolipoprotein E-null (Apoe\uff0d/\uff0d) mice. Here we investigated the effects of incretin-related agents on AAA in a mouse model.', 'Apoe\uff0d/\uff0d mice maintained on an atherogenic diet were subcutaneously infused with saline, Ang II (2000 ng/kg/min), Ang II, and native GLP-1 (2.16 nmol/kg/day) or Ang II and native GIP (25 nmol/kg/day) for 4 weeks. DPP-4I (MK0626, 6 mg/kg/day) was provided in the diet to the Ang II-infused mice with or without incretin receptor antagonists [(Pro3) GIP and exendin (9-39)].', 'AAA occurred in 70% of the animals receiving Ang II. DPP-4I reduced this rate to 40% and significantly suppressed AAA dilatation, fibrosis, and thrombosis. In contrast, incretins failed to attenuate AAA. Incretin receptor blockers did not reverse the suppressive effects of DPP-4I on AAA. In the aorta, DPP-4I significantly reduced the expression of Interleukin-1\u03b2 and increased that of tissue inhibitor of metalloproteinase (TIMP)-2. In addition, DPP-4I increased the ratio of TIMP-2 to matrix metalloproteinases-9.",
            "output": [
                "Does a Dipeptidyl Peptidase-4 Inhibitor but not Incretins suppress Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice?"
            ]
        },
        {
            "id": "task847-d6e4f61324ef4575bfb274f1fb5120ac",
            "input": "To describe the epidemiology of acute hand injuries and hand infections and to describe the factors associated with the transfer of these patients to a level 1 trauma center. In addition, we sought to understand management before transfer.', 'Retrospective review of patients with hand trauma or hand infection transferred to our level 1 trauma center from May 2009 to August 2011. We also identified hospitals with emergency departments (EDs) in our region and surveyed ED providers in these hospitals with regard to acute hand care.', 'A level 1 trauma center in the United States.', 'Four hundred sixty consecutive transfers for acute hand care.', 'The average patient age was 38. Most were male (84%), uninsured (51%), and from another county (59%). The average distance of transfer was 51 miles, and 80% were transferred by ground ambulance. The most common reasons for transfer were amputations (24%), infections (21%), lacerations (17%), and fractures/dislocations (16%). Of the 345 hospitals with an ED surveyed, 71% never had hand surgery coverage.",
            "output": [
                "Do lack of Acute Hand Care in the Southwest United States?"
            ]
        },
        {
            "id": "task847-71ed1aeee0804919b8c0f11a0bbd3cbd",
            "input": "Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited.', 'A cohort (n\\u2009=\\u2009117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n\\u2009=\\u200910), benign ovarian epithelial tumor tissues (n\\u2009=\\u200910), serous borderline ovarian epithelial tumor tissues (n\\u2009=\\u200914), mucous borderline ovarian epithelial tumor tissues (n\\u2009=\\u200911), and invasive ovarian epithelial cancer tissues (n\\u2009=\\u200972) were assessed for Nedd4L protein expression using immunohistochemistry.', 'Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P\\u2009<\\u20090.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P\\u2009<\\u20090.05).",
            "output": [
                "Is nedd4L expression decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue?"
            ]
        },
        {
            "id": "task847-134b54f08cde451883097d2b32f24776",
            "input": "Liver fibrosis develops when hepatic stellate cells (HSC) are activated into collagen-producing myofibroblasts. In non-alcoholic steatohepatitis (NASH), the adipokine leptin is upregulated, and promotes liver fibrosis by directly activating HSC via the hedgehog pathway. We reported that hedgehog-regulated osteopontin (OPN) plays a key role in promoting liver fibrosis. Herein, we evaluated if OPN mediates leptin-profibrogenic effects in NASH.', 'Leptin-deficient (ob/ob) and wild-type (WT) mice were fed control or methionine-choline deficient (MCD) diet. Liver tissues were assessed by Sirius-red, OPN and \u03b1SMA IHC, and qRT-PCR for fibrogenic genes. In vitro, HSC with stable OPN (or control) knockdown were treated with recombinant (r)leptin and OPN-neutralizing or sham-aptamers. HSC response to OPN loss was assessed by wound healing assay. OPN-aptamers were also added to precision-cut liver slices (PCLS), and administered to MCD-fed WT (leptin-intact) mice to determine if OPN neutralization abrogated fibrogenesis.', 'MCD-fed WT mice developed NASH-fibrosis, upregulated OPN, and accumulated \u03b1SMA+ cells. Conversely, MCD-fed ob/ob mice developed less fibrosis and accumulated fewer \u03b1SMA+ and OPN+ cells. In vitro, leptin-treated HSC upregulated OPN, \u03b1SMA, collagen 1\u03b11 and TGF\u03b2 mRNA by nearly 3-fold, but this effect was blunted by OPN loss. Inhibition of PI3K and transduction of dominant negative-Akt abrogated leptin-mediated OPN induction, while constitutive active-Akt upregulated OPN. Finally, OPN neutralization reduced leptin-mediated fibrogenesis in both PCLS and MCD-fed mice.",
            "output": [
                "Is osteopontin a proximal effector of leptin-mediated non-alcoholic steatohepatitis ( NASH ) fibrosis?"
            ]
        },
        {
            "id": "task847-60bebd2ab687437994ba5b72250797bf",
            "input": "Aberrant expression of A20 has been reported in several human malignancies including hepatocellular carcinoma (HCC). However, its clinical relevance and potential role in HCC remain unknown.', 'Quantitative PCR, Western blots and immunohistochemistry analyses were used to quantify A20 expression in HCC samples and cell lines. The correlation of A20 expression with clinicopathologic features was analyzed in a cohort containing 143 patients with primary HCC. Kaplan-Meier curves were used to evaluate the association between A20 expression and patient survival. Functional studies were performed to determine the effects of A20 on proliferation and metastasis of HCC cells in vitro and in vivo.', 'Expression of A20 was increased in HCC tissues and cell lines. Increased expression of A20 was negatively correlated with the tumor size, TNM stage, tumor thrombus formation, capsular invasion and serum AFP levels. Patients with higher A20 expression had a prolonged disease-free survival and overall survival than those with lower A20 expression. Forced expression of A20 significantly inhibited the proliferative and invasive properties of HCC cells both in vitro and in vivo, whereas knockdown of A20 expression showed the opposite effects. Further studies revealed that expression of A20 was inversely correlated with Twist1 levels and NF-\u03baB activity in HCC tissues and cell lines. A20-induced suppression of proliferation and migration of HCC cells were mainly mediated through inhibition of Twist1 expression that was regulated at least partly by A20-induced attenuation of NF-\u03baB activity.",
            "output": [
                "Does a20 suppress hepatocellular carcinoma proliferation and metastasis through inhibition of Twist1 expression?"
            ]
        },
        {
            "id": "task847-ed2d7b6ec50744208b591bc3dadb7fb0",
            "input": "The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB.', 'Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial \u03b2-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial \u03b2-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear \u03b2-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients.",
            "output": [
                "Does endothelial \u03b2-Catenin Signaling be Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis?"
            ]
        },
        {
            "id": "task847-ce404c48b1bb4656afc532abf5812366",
            "input": "Hospital readmissions after surgical operations are considered serious complications and have an impact on health care-associated costs. The Centers for Medicare and Medicaid Services strongly encourage identification and ramification of factors associated with hospital readmissions after operations. Despite advances in endovascular surgery, lower extremity arterial bypass remains the \"gold standard\" treatment for severe, symptomatic peripheral arterial disease. The purpose of this study was to retrospectively review the factors associated with hospital readmission after lower extremity bypass surgery.', 'The 2013 lower extremity revascularization-targeted American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database and generalized 2013 general and vascular surgery NSQIP Participant Use Data File were used for this study. Patient, diagnosis, and procedure characteristics of patients undergoing lower extremity bypass surgery were assessed. Multivariate logistic regression analysis was used to determine independent risk factors for hospital readmission within 30 days after surgery.', 'A total of 2646 patients (65% male, 35% female) were identified in the NSQIP database who underwent lower extremity open revascularization during the year 2013. Indications for operations included tissue loss (39%), rest pain (32%), and severe claudication (25%). Preoperative ankle-brachial indices were 0.4 to 0.9 (32%) and <0.4 (16.5%). A total of 425 patients (16%) were readmitted within 30 days of index operation. Risk factors associated with readmission included wound complication (odds ratio [OR], 8.54; 95% confidence interval [CI], 6.68-10.92; P < .001), need for reoperation (OR, 5.95; 95% CI, 4.45-7.97; P < .001), postoperative myocardial infarction (OR, 2.19; 95% CI, 1.25-3.83; P = .006), wound dehiscence (OR, 8.45; 95% CI, 4.54-15.71; P < .001), organ or space surgical site infection (OR, 7.62; 95% CI, 2.89-20.14; P < .001), postoperative pneumonia (OR, 2.66; 95% CI, 1.28-5.52; P = .009), progressive renal insufficiency (OR, 4.12; 95% CI, 1.52-11.11; P = .005), superficial surgical site infection (OR, 7.37; 95% CI, 5.31-10.23; P < .001), urinary tract infection (OR, 2.67; 95% CI, 1.42-5.01; P = .002), and deep wound infection (OR, 14.0; 95% CI, 7.62-24.80; P < .001).",
            "output": [
                "Is unplanned return to operating room after lower extremity arterial bypass an independent predictor for hospital readmission?"
            ]
        },
        {
            "id": "task847-d70a5e00d500478fb8cc7695da058fd4",
            "input": "The gold standard for the diagnosis of Hirschsprung's disease (HSCR) is the pathologic evaluation of a rectal biopsy that demonstrates the absence of ganglion cells and nerve fibre hypertrophy. However, it has been frequently reported that hypertrophic nerves may not be present in some variants like long-segment HSCR, total colonic aganglionosis, premature and very young infants. The aim of this study was to determine this association.\", \"We performed a retrospective review of the HSCR database at our tertiary care children's hospital from 2000 to 2013. In order to analyse the relationship between the diameter of the nerve fibres and the level of aganglionosis, we classified the patient sample into two groups-fibres \u226440 and >40\\xa0\u03bcm. The groups were statistically compared with P\\xa0<\\xa00.05 being significant.\", 'Rectal biopsies of 92 patients confirmed as HSCR with definitive operation performed at the same institution were reviewed. The mean nerve diameter was 50.1\\xa0\u03bcm (range 20-87.5\\xa0\u03bcm). Nerve fibre diameter \u226440\\xa0\u03bcm was predictive of transition zone above the sigmoid colon. A specificity of 77.3\\xa0% and a likelihood ratio of 2.03 supported this perception. No correlation was noted between nerve fibre diameter and gestational age at birth, birth weight or age at biopsy.",
            "output": [
                "Does aganglionosis with the absence of hypertrophied nerve fibres predict disease proximal to rectosigmoid colon?"
            ]
        },
        {
            "id": "task847-0e489576882c4184bc738541bfd54a01",
            "input": "To describe the prevalence and correlates of hazardous drinking among female sex workers (FSWs) at 13 sites throughout Mexico.', 'FSWs (N = 1089) who were enrolled in a brief sexual risk reduction intervention (Mujer Segura) were queried about their sexual risk and substance use practices and their work contexts. Participants were classified as hazardous or non-hazardous drinkers based on the Alcohol Use Disorders test (AUDIT-C). Logistic regression models were used to examine individual, contextual, and community-level factors as correlates of hazardous drinking.', 'Ninety-two percent of participants reported alcohol consumption in the past month. Among drinkers (N = 1001), 83% met AUDIT-C criteria for hazardous drinking. Factors that were independently associated with hazardous drinking included: drug use in the past month (adjusted odds ratio (AOR) = 3.31; 95% CI 1.29-8.45), being a cigarette smoker (AOR = 1.71; 95% CI 1.13-2.58), being a barmaid or dance hostess (AOR = 3.40; 95% CI 1.95-5.91), alcohol use before or during sex with clients (AOR = 7.78; 95% CI 4.84-12.52), and working in a city with a higher marginalization index (AOR = 1.07; 95% CI 1.04-1.11).",
            "output": [
                "Does prevalence and correlate of Hazardous Drinking among Female Sex Workers in 13 Mexican Cities?"
            ]
        },
        {
            "id": "task847-94c9162298f1449db9a13e9ec80253ad",
            "input": "To clarify actual differences in the neonatal as well as maternal outcome between completed twin vaginal delivery and cesarean delivery.', \"We collected the data from women with a twin pregnancy who delivered two live fetuses between 1 January and 31 December 2014 at 20 teaching\\u2009hospitals (1) (1) PARTICIPANTS: Adachi Hospital, Hyogo Prefectural Amagasaki General Medical Center, Japan Baptist Hospital, Kitano Hospital, Kobe City Medical Center General Hospital, Kosaka Women's Hospital, Kurashiki Central Hospital, Kyoto University Hospital, Mitsubishi Kyoto Hospital, Nagahama Red Cross Hospital, National Hospital Organization Kyoto Medical Center, National Hospital Organization Osaka National Hospital, Osaka Red Cross Hospital, Otsu Municipal Hospital, Otsu Red Cross Hospital, Red Cross Wakayama Medical Center, Saiseikai Noe Hospital, Shizuoka General Hospital, Takamatsu Red Cross Hospital and Tenri Hospital. in Japan. Only the cases that were retrospectively regarded as eligible for planned vaginal delivery were analyzed according to the actual mode of delivery.\", \"Umbilical arterial blood pH (UmA-pH) of the second twin was slightly but significantly lower in the vaginal delivery group (7.26\\u2009\u00b1\\u20090.009) than in a cesarean delivery group (7.30\\u2009\u00b1\\u20090.006). Vaginal delivery was the only independent risk factor for second twin's UmA-pH \\u2009<7.20. Intrapartum blood loss was significantly larger in the cesarean delivery group (1444\\u2009\u00b1\\u200963\\u2009g) than in the vaginal delivery group (820\\u2009\u00b1\\u2009109\\u2009g). Cesarean delivery was an independent risk factor for intrapartum blood loss\\u2009\u22651500\\u2009g.",
            "output": [
                "Is twin vaginal delivery associated with lower umbilical arterial blood pH of the second twin and less intrapartum blood loss?"
            ]
        },
        {
            "id": "task847-c22557a2ca624a49bbbfdf2918bf93a5",
            "input": "Chronic administration of selective cyclooxygenase-2 (COX-2) inhibitors leads to an increased risk of adverse cardiovascular events, including myocardial infarction and stroke. Vascular smooth muscle cell (VSMC) calcification, a common complication of chronic kidney disease, is directly related to cardiovascular morbidity and mortality. Here, we tested whether specific COX-2 inhibition affects vascular calcification during chronic renal failure.', 'The COX-2-specific inhibitors NS398 and SC236 significantly increased high-phosphate (Pi)-induced VSMC calcification. Similarly, COX-2(-/-) VSMCs, COX-2(-/-) aortas rings treated with high Pi and adenine diet-induced COX-2(-/-) chronic renal failure mice displayed enhanced calcium deposition. Metabolomic analysis revealed the differential suppression of PGE2 production by COX-1- and COX-2-specific inhibitors in high-Pi-stimulated VSMCs, indicating the involvement of PGE2 during COX-2 inhibition-aggravated vascular calcification. Indeed, exogenous PGE2 reduced alkaline phosphatase activity, osteogenic transdifferentiation, apoptosis, and calcification of VSMCs. In accordance, downregulation of microsomal prostaglandin E synthase (mPGES)-1 in VSMCs, mPGES-1(-/-) aorta with high-Pi stimulation and mPGES-1(-/-) chronic renal failure mice resulted in enhanced vascular mineralization. Further applications of RNAi and specific antagonists for PGE2 receptors indicated EP4 may mediate PGE2-inhibited vascular calcification.",
            "output": [
                "Does microsomal Prostaglandin E Synthase-1-Derived PGE2 inhibit Vascular Smooth Muscle Cell Calcification?"
            ]
        },
        {
            "id": "task847-e15a54581cb84c8b889c8c0c374cf92b",
            "input": "To examine the expression of Twist1 in cervical cancer and to explore its biological function in the progression of cervical cancer.\\u2029', 'The expressions of Twist1 in 32 cervical cancers and matched normal tissues were examined by immunohistochemistry (IHC). Cell invasive ability and the expression of invasion-related genes were determined in RNAi-based Twist1-silencing HeLa cells. The relationship between Twist1 and microRNA-33a (miR-33a) in cervical cancer was studied by Pearson correlation analysis, and the roles of miR-33a in regulation of Twist1 and cell invasiveness were studied.\\u2029', 'The positive expression rate of Twist1 was 75.0% (24/32) and 21.9% (7/32) in the cervical cancer and the matched normal tissues, respectively, with significant difference between them (P<0.05). Twist1 shRNA significantly decreased the invasiveness of HeLa cells (P<0.05). Compared with the matched normal tissues, the expression of miR-33a was increased in the cervical cancer tissues, which was negatively correlated with Twist1 (r=-0.661, P<0.05). Overexpression of miR-33a could significantly suppress Twist1 expression as well as cell invasiveness (P<0.05).\\u2029",
            "output": [
                "Does [ MicroRNA-33a regulate the invasion of cervical cancer cells via targeting Twist1 ]?"
            ]
        },
        {
            "id": "task847-e4d3050dcf8448b689b784d1fd2230b4",
            "input": "To determine the inhibitory effect of miRNA-381 on renal carcinoma invasion and to explore the underlying mechanisms.\\u2029', 'After up-regulation of miRNA-381, the inhibitory effect of miR-381 on cell invasion was investigated. We screened the target genes of miRNA-381 in a database (starBase) through combination of five programs including targetscan, picTar, RNA22, PITA and miRanda. Then, the predicted targeting genes were verified by the dual luciferase reporter assay. We also examined the expression of miRNA-381 and its target genes in renal cancer cells and tissues.\\u2029', \"Transfection and up-regulation of miRNA-381 resulted in a significant decrease in trans-membrane cell numbers and the ability of renal cell invasion. Bioinformatics analysis showed that CREB binding protein (CBP), \u03b2-catenin and lymphoid enhancer binding factor-1 (LEF-1) were the potential targets of miRNA-381. In the luciferase reporter gene system, co-transfection of miRNA-381 with the 3'UTR of wild-type target gene led to a significant decrease in luciferase activity. The expression of miRNA-381 was decreased in various renal cancer cells, and it was particularly lower in highly metastatic cell lines (786-OHM). On the contrary, the expression levels of miRNA-381 target genes (CBP, \u03b2-catenin and LEF-1) were significantly increased in cells and tissues.\\u2029",
            "output": [
                "Does [ MiRNA-381 inhibit the invasion of renal carcinoma and the underlying mechanisms ]?"
            ]
        },
        {
            "id": "task847-e446c0f7f92f4c8492a9707a6daf78e9",
            "input": "Preventing or reducing amyloid-beta (A\u03b2) accumulation in the brain is an important therapeutic strategy for Alzheimer's disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble A\u03b2 clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent.\", 'Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in A\u03b2 accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignificant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples.",
            "output": [
                "Does deletion of aquaporin-4 in APP/PS1 mice exacerbate brain A\u03b2 accumulation and memory deficits?"
            ]
        },
        {
            "id": "task847-d4a78abfd0f948f29a2430cd99e9c664",
            "input": "The fetal inflammatory response (FIR) in placental membranes to an intrauterine infection often precedes premature birth raising neonatal mortality and morbidity. However, the precise molecular events behind FIR still remain largely unknown, and little has been investigated at gene expression level.', 'We collected publicly available microarray expression data profiling umbilical cord (UC) tissue derived from the cohort of extremely low gestational age newborns (ELGANs) and interrogate them for differentially expressed (DE) genes between FIR and non-FIR-affected ELGANs.', 'We found a broad and complex FIR UC gene expression signature, changing up to 19% (3,896/20,155) of all human genes at 1% false discovery rate. Significant changes of a minimum 50% magnitude (1,097/3,896) affect the upregulation of many inflammatory pathways and molecules, such as cytokines, toll-like receptors, and calgranulins. Remarkably, they also include the downregulation of neurodevelopmental pathways and genes, such as Fragile-X mental retardation 1 (FMR1), contactin 1 (CNTN1), and adenomatous polyposis coli (APC).",
            "output": [
                "Does umbilical cord gene expression reveal the molecular architecture of the fetal inflammatory response in extremely preterm newborns?"
            ]
        },
        {
            "id": "task847-d3392a2b84724ef0871cf233d6dca898",
            "input": "To determine whether the cellular physiology of the lens actively maintains the optical properties of the lens and whether inhibition of lens transport affects overall visual quality.', 'One lens from a pair of bovine lenses was cultured in artificial aqueous humor (AAH), while the other was cultured in either AAH-High-K+ or AAH + 0.1 mM ouabain for 4 hours. Lens pairs or whole enucleated eyes were then imaged in 4.7 Tesla (T) high-field small animal magnet. Lens surface curvatures, T1 measurements of water content, and T2 measurements of water/protein ratios were extracted from cultured lenses, while the geometrical parameters that define the optical pathway were obtained from whole eyes. Gradients of refractive index (GRIN), calculated from T2 measurements, and the extracted geometric parameters were inputted into optical models of the isolated lens and the whole bovine eye.', 'Inhibiting circulating fluxes by inhibiting the Na/K-ATPase with ouabain or depolarization of the lens potential by High K+ caused changes to lens water content, the water/protein ratio (GRIN) and surface geometry that manifested as an increase in optical power and a decrease in negative spherical aberration in cultured lenses. Changes to optical properties of the lens resulted in a myopic shift that impaired vision quality in the optical model of the bovine eye.",
            "output": [
                "Does active Maintenance of the Gradient of Refractive Index be Required to Sustain the Optical Properties of the Lens?"
            ]
        },
        {
            "id": "task847-59e6351dc313459fb831153e9008116c",
            "input": "Are the levels of circulating cell-derived microparticles (cMPs) in patients with recurrent miscarriage (RM) associated with the antiphospholipid syndrome (APS)?",
            "output": [
                "Are higher levels of procoagulant microparticles in women with recurrent miscarriage associated with antiphospholipid antibodies?"
            ]
        },
        {
            "id": "task847-4a0eb204df06480583c957c034f8b5a5",
            "input": "TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging.', 'We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2\u03b1-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities.",
            "output": [
                "Is meis2 essential for cranial and cardiac neural crest development?"
            ]
        },
        {
            "id": "task847-15c22fb4854e4886affc2f2d3ab21bee",
            "input": "To determine the effects of endostatin on vascular growth factor receptor 2 (VEGFR2) expression in non-small cell lung cancer (NSCLC) cells and the mechanisms underlying its radiosensitizing effect.', 'VEGFR2 mRNA levels were determined in different NSCLC cell lines using qRT-PCR. RT-PCR and Western blot assays were used to assess the expression of mRNA and proteins. The radiosensitivity of the cells was determined by colony-formation assays; and cell apoptosis and cell cycle distribution were determined by flow cytometry.', 'VEGFR2 mRNA levels differed among the five NSCLC cell lines (P < 0.01), with the highest expression in Calu-1 cells and lowest in A549 cells. Endostatin significantly inhibited the growth of Calu-1 cells (P < 0.01) (IC20 = 296.5 \u03bcg/ml), and the expression of VEGFR2 and HIF-1\u03b1 (P < 0.05). Phosphorylation of protein kinase B (Akt), extracellular signal-regulated kinases 1/2 (ERK1/2), and p38 were significantly lower in endostatin-treated cells than control (P < 0.05). Endostatin enhanced the radiosensitivity of Calu-1 cells to SER = 1.38 and induced apoptosis (P < 0.01) and G2/M blockage (P < 0.01). However, endostatin had limited effects on A549 cells. Compared with Calu-1 cells, there was not significantly effects on cell radiosensitivity (SER = 1.09).",
            "output": [
                "Does endostatin exert radiosensitizing effect in non-small cell lung cancer cells by inhibiting VEGFR2 expression?"
            ]
        },
        {
            "id": "task847-2d299099231b40c68a933df188660460",
            "input": "To investigate the diagnostic performance of perfusion single-photon emission computed tomography/computed tomography (Q-SPECT/CT) in patients suspected to have pulmonary embolism (PE) but with indeterminate computed tomographic pulmonary angiography (CTPA) or planar ventilation/perfusion (V/Q) scans.', 'This retrospective study included two groups of patients. Group I consisted of 49 patients with nondiagnostic CTPA. These 49 patients underwent subsequent V/Q scans. Further Q-SPECTs were obtained in patients with indeterminate planar images and fused with existing CTPA. Group II consisted of 182 non-CTPA patients with indeterminate V/Q scans. These 182 patients underwent further Q-SPECT and separate noncontrast low-dose CT chest. Fusion Q-SPECT/CT scans were obtained through FDA-approved software and interpreted according to published criteria as positive, negative, or indeterminate for PE. Upon retrospective analyses, the final diagnosis was made using composite reference standards including all available clinical and imaging information for at least 6-month follow-up.', 'In group I patients, 1 was positive, 24 were negative, and another 24 (49\\xa0%, 24/49) were indeterminate. In the subsequent 24 Q-SPECT/CTPAs, 4 were positive, 19 were negative, and 1 was indeterminate (4.2\\xa0%, 1/24). In group II patients, 9 (4.9\\xa0%, 9/182) were indeterminate, 33 were positive, and 140 were negative. The combined nondiagnostic rate for Q-SPECT/CT was only 4.9\\xa0% (10/206). There was six false-negative and one false-positive Q-SPECT/CT examinations. The sensitivity, specificity, and positive and negative predictive value of Q-SPECT/CT were 85.7\\xa0% (36/42), 99.4\\xa0% (153/154), 97.3\\xa0% (36/37) and 96.2\\xa0% (153/159), respectively.",
            "output": [
                "Does software-Based Hybrid Perfusion SPECT/CT provide Diagnostic Accuracy When Other Pulmonary Embolism Imaging Is Indeterminate?"
            ]
        },
        {
            "id": "task847-7a5a9bb1e9304b04b6c04f4898d79f41",
            "input": "Increased consumption of a high-fat (HF) diet is a salient contributor to obesity; however, how diminished satiation signaling contributes to overconsumption and obesity development remains poorly understood.', 'Using obese-prone (OP) and obese-resistant (OR) rats, we tested feeding responses to intragastric liquid meal replacement, prior and after HF feeding. Next, chow- and HF-fed OP and OR rats were tested for sensitivity to intraduodenal glucose, intralipid, and meal replacement loads. To examine the role of glucagon-like peptide-1 (GLP-1) and vagal signaling, animals were treated with exendin-9, GLP-1 receptor antagonist, prior to meal replacement infusion, and Fos-like immunoreactivity (Fos-Li) in the dorsal hindbrain was examined after infusion.', 'OP and OR rats reduced chow intake equally following gastric liquid meal; however, after 2 weeks of HF feeding, intragastric meal replacement reduced food intake less in OP than OR. Similarly, HF feeding, but not chow, diminished the suppressive effects of intraduodenal meal replacement, glucose, and intralipid in OP compared to OR. This effect was associated with lower Fos-Li expression in the dorsal hindbrain of OP rats. Finally, exendin-9 failed to attenuate reduction of food intake by meal replacement in OP rats during HF feeding.",
            "output": [
                "Does impaired GLP-1 signaling contribute to reduced sensitivity to duodenal nutrients in obesity-prone rats during high-fat feeding?"
            ]
        },
        {
            "id": "task847-ed61f0312c1c4b2797ad2c9e90bcffa3",
            "input": "The present study is to investigate the pathological changes in rabbits with traumatic optic neuropathy (TON), as well as the effect of fasudil on the lesions.', 'A total of 144 New Zealand rabbits were successfully established as TON models. Twelve hours after surgery, the rabbits in control, dexamethasone, and fasudil groups were administrated with saline, dexamethasone, and fasudil via ear veins, respectively. Then, retinas of the rabbits were obtained at 72 h and on days 7, 14 and 21 after surgery. The pathological changes in retina and optic nerves were observed by hematoxylin and eosin staining and transmission electron microscopy. The expression levels of Rho-associated genes were measured using quantitative real-time polymerase chain reaction.', 'In control group, the axons were swelling, and mitochondria showed vacuolation after optic nerve crush. Mitochondria were swelled slightly in dexamethasone group. By contrast, nerves in fasudil group were repaired. Retinal ganglion cells in control group were reduced significantly due to optic nerve crush. The loss of retinal ganglion cells was alleviated in fasudil group. Quantitative real-time polymerase chain reaction showed that the expression of Rho-associated genes were down-regulated.",
            "output": [
                "Does fasudil alleviate traumatic optic neuropathy by inhibiting Rho signaling pathway?"
            ]
        },
        {
            "id": "task847-1f22796191de418baefcf09ea5c9c644",
            "input": "Estrogen-related receptor alpha (ERR\u03b1) signaling has recently been implicated in breast cancer. We investigated the clinical value of ERR\u03b1 in randomized cohorts of tamoxifen-treated and adjuvant-untreated patients.', 'Cox proportional hazards regression was used to evaluate the significance of associations between ERR\u03b1 gene expression levels and patient DMFS in a previously published microarray dataset representing 2,000 breast tumor cases derived from multiple medical centers worldwide. The 912 tumors used for immunostaining were from a tamoxifen-randomized primary breast cancer trial conducted in Stockholm, Sweden, during 1976-1990. Mouse model was used to study the effect of tamoxifen treatment on lung colonization of MDA-MB-231 control cells and MDA-MB-231 cells with stable knockdown of ERR\u03b1. The phenotypic effects associated with ERR\u03b1 modulation were studied using immunoblotting analyses and wound-healing assay.', 'We found that in ER-negative and triple-negative breast cancer (TNBC) adjuvant-untreated patients, ERR\u03b1 expression indicated worse prognosis and correlated with poor outcome predictors. However, in tamoxifen-treated patients, an improved outcome was observed with high ERR\u03b1 gene and protein expression. Reduced ERR\u03b1 expression was oncogenic in the presence of tamoxifen, measured by in vitro proliferation and migration assays and in vivo metastasis studies.",
            "output": [
                "Does eRR\u03b1 be a Marker of Tamoxifen Response and Survival in Triple-Negative Breast Cancer?"
            ]
        },
        {
            "id": "task847-4c0384672c524309a675de2698c05bc4",
            "input": "MicroRNA-340 (miR-340) is deregulated in many human cancers in correlation with tumor progression. Recent studies have found that microRNAs play key roles in energy metabolism. This study explored the contributions of miR-340 to the metabolic shift in oral squamous cell carcinoma (OSCC).', 'MiR-340 expression was measured by real-time polymerase chain reaction. MiR-340 mimics, miR-340 inhibitor, and scramble small interfering RNA were transfected into SAS human tongue SCC cells to observe their effects on cell proliferation, colony formation, lactate secretion, and glucose uptake rate. Moreover, the relation between the level of miR-340 and glucose transporter-1 (Glut1) was investigated.', 'The expression of miR-340 was decreased and thus induced a metabolic switch in oral cancer cells. The decrease in miR-340 increased Glut1 expression, leading to an increase in lactate secretion and glucose uptake rate. The altered metabolism induced by miR-340 resulted in the rapid proliferation of oral cancer cells.",
            "output": [
                "Does microRNA-340 mediate Metabolic Shift in Oral Squamous Cell Carcinoma by Targeting Glucose Transporter-1?"
            ]
        },
        {
            "id": "task847-8a151170cc9f470fa05c5ae408a18c3a",
            "input": "Genetic factors are reported to affect fracture incidence. Many groups have explored the correlation of fracture risk with ESR1 IVS1-397T>C. The observed associations, however, are largely inconsistent. This meta-analysis of data from early-released studies was performed in an effort to determine the role of IVS1-397T>C in fracture.', 'Relevant studies were searched through Pubmed, Embase, ScienceDirect, and Wiley Online Library databases. 16 studies meeting all selection criteria were finally identified. We calculated ORs with 95% CIs to assess risk of fracture. Subgroup analyses were performed by subtype, ethnicity and gender.', 'Data on 2916 cases and 19170 controls were analyzed in the meta-analysis. Overall, we found moderately decreased risk in association with IVS1-397 CC genotype (OR = 0.82, 95% CI = 0.73-0.92; OR = 0.84, 95% CI = 0.76-0.94). The decrease persisted in both hip fracture (OR = 0.82, 95% CI = 0.71-0.94; OR = 0.83, 95% CI = 0.73-0.94) and vertebral fracture (OR = 0.67, 95% CI = 0.50-0.91; OR = 0.78, 95% CI = 0.64-0.97; OR = 0.82, 95% CI = 0.68-0.98) when data were stratified by subtype. We also found a significant trend of decreasing risk in relation to the CC genotype in Caucasian, male and female. All fixed-effects meta-analysis results were homogeneous.",
            "output": [
                "Does estrogen receptor \u03b1 ( ESR1 ) IVS1-397T > C polymorphism lower risk of fracture?"
            ]
        },
        {
            "id": "task847-771a5cbec9334674bbc7479a7c1d02d6",
            "input": "Willis-Ekbom disease (WED), also called restless legs syndrome (RLS), is a neurologic sensorimotor disease that may be associated with cardiovascular disease. Given high morbidity and mortality rates of cardiovascular disease worldwide, we assessed the relation between WED/RLS and cardiovascular health risks in a native South American population. We prospectively analyzed data from The Atahualpa Project of Ecuadorian adults aged 40\\xa0years and older. Physicians interviewed consented persons on the health behavior and health factors of the American Heart Association (AHA) for ideal cardiovascular health in adults and underwent fasting laboratory blood collection and blood pressure evaluation. Certified neurologists conducted face-to-face interviews using the International Restless Legs Syndrome Study Group (IRLSSG) field instrument. Persons testing positive for WED/RLS and age-and sex-matched controls underwent confirmatory physical examinations conducted by a neurologist and a sleep specialist to whom IRLSSG designation was blinded.', 'Of 665 persons, 94 (14\\xa0%) tested positive in IRLSSG; 40 (6\\xa0%) had a diagnosis of WED/RLS after neurologic examination and interview. Patients with WED/RLS were younger (53.5 vs 59.9\\xa0years, P\\u2009=\\u2009.001), without significant differences in sex ratios. Among AHA risk factors, only obesity was significantly more prevalent among patients with WED/RLS (42.5\\xa0% vs 23.5\\xa0%, P\\u2009=\\u2009.01). However, after adjustment for confounders, body mass index was not significantly associated with WED/RLS.",
            "output": [
                "Is willis-Ekbom disease associated with poor cardiovascular health in adults?"
            ]
        },
        {
            "id": "task847-47f15aa1be854f6c99333376378d801c",
            "input": "Cam impingement as a known sequelae of slipped capital femoral epiphysis (SCFE) has led to speculation that subclinical SCFEs may be the causative factor in idiopathic cam morphology; alternatively, others have implicated an abnormal extension of the growth plate as a causative factor.', 'To investigate the growth plate tilt angle in 4 patient cohorts: normal patients, patients with idiopathic cam morphology (CamIP), patients with cam morphology secondary to known SCFE (CamSCFE), and patients with incidental findings of an asymptomatic cam (Camasymp).', 'Case-control study; Level of evidence, 3.', 'A database of 192 computed tomography scans of abdomens/pelvises of patients (ages, 5-19 years) with no known orthopaedic issues, reformatted to neutral tilt, inclination, and rotation, were utilized for the normal cohort, the Camasymp cohort, and to create an age- and sex-matched control cohort. In addition, a retrospective review of all patients treated for femoroacetabular impingement (FAI) with preoperative advance imaging was conducted, and patients were separated to CamIP and CamSCFE cohorts. The alpha angle and tilt angle were measured on each hip. Statistical analysis was performed.', 'The mean tilt angle among the normal patients was 12.1\u00b0, with 1.9% of the variation in tilt angle being explained by age; each additional year of age decreased the tilt angle by 0.27\u00b0 (P = .008). The tilt angle for the CamSCFE cohort (mean, 44.5\u00b0) was found to be significantly greater than both the CamIP cohort (mean, 5.9\u00b0; P < .001) and the control cohort (mean, 12.8\u00b0; P < .001). The tilt angle for the CamIP cohort was found to be significantly less than the control cohort (P = .003). The alpha angle and tilt angle were positively correlated in the CamIP cohort, but no correlation was found in the other cohorts. The mean tilt angle of the 18 hips in the Camasymp cohort was 13.9\u00b0 \u00b1 11.5\u00b0 (range, -12\u00b0 to 37\u00b0), with 12 hips (67%) in the tilt angle range of CamIP cohort and 6 in the tilt angle range of CamSCFE.",
            "output": [
                "Is idiopathic Cam Morphology Caused by Subclinical Slipped Capital Femoral Epiphysis : An MRI and CT Study?"
            ]
        },
        {
            "id": "task847-bd7a67f3ea9b4de89fe8c5bcaa501f9b",
            "input": "To determine if temporomandibular joint chondrocyte apoptosis is induced in rats with dental biomechanical stimulation and what a role TNF takes.', 'Thirty-two rats were divided into 4 groups (n = 8/group) and exposed to incisor mal-occlusion induced by unilateral anterior crossbite biomechanical stimulation. Two groups were sampled at 2 or 4 weeks. The other two groups were treated with local injections of a TNF inhibitor or PBS into the temporomandibular joints area at 2 weeks and then sampled at 4 weeks. Twenty-four rats either served as unilateral anterior crossbite mock operation controls (n = 8/group) with sampling at 2 or 4 weeks or received a local injection of the TNF inhibitor at 2 weeks with sampling at 4 weeks. Chondrocytes were isolated from the temporomandibular joints of 6 additional rats and treated with TNF in vitro. Joint samples were assessed using Hematoxylin&eosin, Safranin O, TUNEL and immunohistochemistry staining, real-time PCR, fluorogenic activity assays and Western blot analyses. The isolated chondrocytes were also analyzed by flow cytometry.', 'Unilateral anterior crossbite stimulation led to temporomandibular joint cartilage degradation, associated with an increase in TUNEL-positive chondrocytes number, caspase-9 expression levels, and the release of cytochrome c from mitochondria at 2 weeks without changes in TNF and caspase-8 levels until after 4 weeks. TNF stimulated apoptosis of the isolated chondrocytes and up-regulated caspase-8 expression, but did not change caspase-9 expression levels. Local injection of TNF inhibitor down-regulated caspase-8 expression and reduced TUNEL-positive cell number, but did not reverse cartilage thickness reduction, caspase-9 up-regulation or cytochrome c release.",
            "output": [
                "Does tNF accelerate Death of Mandibular Condyle Chondrocytes in Rats with Biomechanical Stimulation-Induced Temporomandibular Joint Disease?"
            ]
        },
        {
            "id": "task847-6d950108e8c64234b8c75ceecc1e784f",
            "input": "Evidence-based guidelines concerning the older head and neck cancer (HNCA) patient are lacking. Accurate patient selection for optimal care management is therefore challenging. We examined if geriatric assessment is indicative of long-term health-related quality of life (HRQOL) and overall survival in this unique population.', \"All HNCA patients, aged \u226565 years, eligible for curative radio(chemo)therapy were evaluated with the Geriatric-8 (G-8) questionnaire and a comprehensive geriatric assessment (CGA). Euroqol-5 dimensions (EQ-5D) and survival were collected until 36 months post treatment start. Repeated measures ANOVA was applied to analyse HRQOL evolution in 'fit' and 'vulnerable' patients, defined by G-8. Kaplan-Meier curves and cox proportional hazard analysis were established for determination of the prognostic value of geriatric assessments. Quality-adjusted survival was calculated in both patient subgroups.\", 'One hundred patients were recruited. Seventy-two percent of patients were considered vulnerable according to CGA (\u22652 abnormal tests). Fit patients maintained a relatively acceptable long-term HRQOL, whilst vulnerable patients showed significantly lower median health states. The difference remained apparent at 36 months. Vulnerability, as classified by G-8 or CGA, came forward as independent predictor for lower EQ-5D index scores. After consideration of confounders, a significantly lower survival was observed in patients defined vulnerable according to G-8, compared to fit patients. A similar trend was seen based on CGA. Calculation of quality-adjusted survival showed significantly less remaining life months in perfect health in vulnerable patients, compared to fit ones.",
            "output": [
                "Does g-8 indicate overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy?"
            ]
        },
        {
            "id": "task847-9cbdfe22f4574db9a899fb4b4929577c",
            "input": "Nanoparticles (NPs) in contact with biological fluids become covered by a tightly bound layer of proteins, the \"protein corona\", and it is largely accepted that this corona gives a new identity to NPs in biological milieu. We here consider the exposing scenario of NPs through an environmental route exemplified by the use of hydrophobins, highly adhesive proteins that are secreted into the environment in large quantities by fungi. HFBII of Trichoderma reesei has been used as a model protein and we have shown strong binding to polystyrene NPs of different sizes and surface groups. Hydrophobin coated NPs are shown to strongly increase the stability and the dispersion when exposed to human plasma compared to pristine ones particles. It is also shown that the presence of hydrophobin on the NPs results in an attenuated protein corona formation, in a different corona composition, and we also show that hydrophobin remained strongly associated to the NPs in competition with plasma proteins. As a conclusion we therefore suggest that the route of exposure of nanoparticles strongly affects their surface properties and their possible physiological behavior.",
            "output": [
                "Does an environmental route of exposure affect the formation of nanoparticle coronas in blood plasma?"
            ]
        },
        {
            "id": "task847-4536533ff95048f2a32685c9436d1a66",
            "input": "Our previous data demonstrated that targeting non-homologous end-joining repair (NHEJR) yields a higher radiosensitivity than targeting homologous recombination repair (HRR) to heavy ions using DNA repair gene knockouts (KO) in mouse embryonic fibroblast (MEF). In this study, we determined if combining the use of an NHEJR inhibitor with carbon (C) ion irradiation was more efficient in killing human cancer cells compared with only targeting a HRR inhibitor.', 'The TP53-null human non-small cell lung cancer cell line H1299 was used for testing the radiosensitizing effect of NHEJR-related DNA-dependent protein kinase (DNA-PK) inhibitor NU7026, HRR-related Rad51 inhibitor B02, or both to C ion irradiation using colony forming assays. The mechanism underlying the inhibitor radiosensitization was determined by flow cytometry after H2AX phosphorylation staining. HRR-related Rad54-KO, NHEJR-related Lig4-KO, and wild-type TP53-KO MEF were also included to confirm the suppressing effect specificity of these inhibitors.', 'NU7026 showed significant sensitizing effect to C ion irradiation in a concentration-dependent manner. In contrast, B02 showed a slight sensitizing effect to C ion irradiation. The addition of NU7026 significantly increased H2AX phosphorylation after C ion and x-ray irradiations in H1299 cells, but not B02. NU7026 had no effect on radiosensitivity to Lig4-KO MEF and B02 had no effect on radiosensitivity to Rad54-KO MEF in both irradiations.",
            "output": [
                "Does combining carbon ion irradiation and non-homologous end-joining repair inhibitor NU7026 efficiently kill cancer cells?"
            ]
        },
        {
            "id": "task847-1c6d5b2bfe3640a09924fcf65fa40f76",
            "input": "Recent randomized trials suggest that intensive glycaemic control fails to reduce heart failure-related events in patients with diabetes. The molecular cues underlying persistent myocardial damage despite normoglycaemia restoration remain elusive. MicroRNAs (miRNAs), a class of small non-coding RNAs, orchestrate transcriptional programs implicated in adverse cardiac remodelling. The present study investigates whether miRNAs participate to hyperglycaemic memory in the diabetic heart.', 'miRNA landscape was assessed by Mouse miRNome miRNA PCR Arrays in left ventricular specimens collected from 4-month-old streptozotocin-induced diabetic mice, with or without intensive glycaemic control by slow-release insulin implants. A dysregulation of 316 out of 1008 total miRNAs was observed in the diabetic hearts when compared with controls. Of these, 209 were up-regulated and 107 were down-regulated by >2.0-fold. Interestingly enough, the expression of 268 of those miRNAs remained significantly altered in diabetic mice even after subsequent normoglycaemia. Ingenuity pathway analysis revealed that dysregulated miRNAs were implicated in myocardial signalling networks triggering apoptosis (miR-320b, miR-378, miR-34a), fibrosis (miR-125b, miR-150, miR-199a, miR-29b, miR30a), hypertrophic growth (miR-1, miR-150, miR-199a, miR-133a, miR-214, miR-29a, miR-125b, miR-221, miR-212), autophagy (miR-133a, miR-221, miR-212, miR30a), oxidative stress (miR-221, miR-146a, miR-34a, miR-210, miR-19b, miR-125b, miR27a, miR-155), and heart failure (miR-423, miR-499, miR-199a), respectively.",
            "output": [
                "Does microRNA profiling unveil hyperglycaemic memory in the diabetic heart?"
            ]
        },
        {
            "id": "task847-1e2390d743664fa38cae0adc13673654",
            "input": "The tumor susceptibility gene 101 (TSG101) was originally identified as a tumor-suppressor gene that mediates many molecular and biological processes, such as ubiquitination, endosomal trafficking, cell survival, and virus budding, but its role in hepatocellular carcinoma (HCC) is currently unknown.', 'We assessed the expression of TSG101 in HCC and paracancerous tissues using qPCR. Then, we used the TSG101-specific siRNA mix to disrupt the expression of TSG101 to investigate the subsequent effect on human hepatoma-7 (Huh7) cells. Western blot was used to detect the protein expression of TSG101 and other molecules. Cell growth assay was performed using CCK8. Transwell assay was used to investigate the migration and invasion ability of Huh7 cells after transfection with of TSG101 siRNA. Flow cytometry was used to estimate the effect of TSG101 knockdown on cell cycle and apoptosis. Confocal laser scanning microscopy was used to observe the actin filaments change and the formation of autophagy.', 'TSG101 was over-expressed in HCC tissues. TSG101 silence was able to suppress Huh7 cell proliferation, migration, and invasion. Furthermore, silencing of TSG101 could induce cell cycle arrest at G1 phase and inhibit the expression of cyclin A and cyclin D, while up-regulating the expression of CDK2. The mechanism might be induction of autophagic cell death and inactivation of Akt and ERK1/2.",
            "output": [
                "Does tSG101 Silencing suppress Hepatocellular Carcinoma Cell Growth by Inducing Cell Cycle Arrest and Autophagic Cell Death?"
            ]
        },
        {
            "id": "task847-d8c56ff03d724afcbcd83e76671ec080",
            "input": "Anti-epileptic drugs (AEDs) and the ketogenic diet (KD) are often used concomitantly in children with refractory epilepsy. It has been hypothesised that certain AEDs may interfere with KD. The purpose of this study was to elucidate relationships between efficacy of KD and use of specific AEDs.', \"A retrospective study was performed in 71 children with refractory epilepsy starting the KD between 2008 and 2014 in Erasmus University Hospital Sophia Children's Hospital. Efficacy of the KD (defined as 50% seizure reduction) was evaluated after three months of treatment and related to the AEDs used.\", 'The KD was successful after three months in 61% of the children (N=71). Efficacy was significantly reduced if children (n=16) used lamotrigine (31%) at diet initiation or in the course of the diet, compared to other antiepileptic drugs (69%) (p=0.006). In comparison to children using other antiepileptic drugs, the percentage of children that had adequate ketosis was significantly reduced in case of lamotrigine use (p=0.049).",
            "output": [
                "Is concomitant lamotrigine use associated with decreased efficacy of the ketogenic diet in childhood refractory epilepsy?"
            ]
        },
        {
            "id": "task847-751aae7269b04cc1945b086a16bef211",
            "input": "Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling.', 'We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt-sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta-1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%).",
            "output": [
                "Do macrophages dictate the progression and manifestation of hypertensive heart disease?"
            ]
        },
        {
            "id": "task847-5a3a4f9c644c4cd38a81932be7b4dabc",
            "input": "There have been conflicting results from studies to determine whether factors unrelated to endoscopist skill, such as fatigue, affect the quality of screening colonoscopy. We studied the effects of human and system factors on screening colonoscopy withdrawal time and likelihood of detecting an adenoma in a large cohort of patients.', 'We performed a retrospective analysis of operation and quality improvement data in colonoscopies performed at single academic medical center from November 2012 through February 2014. We collected data from the Northwestern Medicine Enterprise Data Warehouse on endoscopy procedure reports, patient demographics, and pathology reports of all patients undergoing endoscopy. We identified all screening colonoscopies during the study period and determined whether an adenoma was identified in each screening colonoscopy procedure. Our study included data from 7004 screening colonoscopies of patients 50-75 years old performed by endoscopists who performed at least 100 screening colonoscopies during the study period (n = 18).', 'Approximately 27% of procedures began on time; the median colonoscope insertion time was 5.9 minutes (interquartile range, 4.0-8.6). In multivariable logistic regression analysis adjusting for covariates and endoscopist-level clustering, adenoma detection was not associated with procedure delay (P = .48), hour of day (P = .40), or performing the second of 2 colonoscopy blocks in 1 day (P = .88). Adenoma detection was associated with insertion time overall (P = .006), but there was no consistent directional relationship across insertion quintiles.",
            "output": [
                "Are procedure Delays and Time of Day Associated With Reductions in Quality of Screening Colonoscopies?"
            ]
        },
        {
            "id": "task847-640ca589c92247f0beecf6605e7d8784",
            "input": "To evaluate the neurosensory outcome of management of damaged inferior alveolar nerves caused by endodontic overfilling and to assess the efficacy of delayed surgical intervention.', 'Nine patients who underwent surgical removal of extruded endodontic material were included. All patients were evaluated for neurosensory function using a set of standardized tests. The outcome of surgical intervention was evaluated through patient interview and quantitative statistical analysis.', 'Surgical procedures included foreign body removal, microsurgical external/internal decompression, excision of neuroma followed by nerve repair, and excision of damaged nerve segment with interpositional nerve graft. Seven of the nine patients had significant improvement according to the follow-up neurosensory assessment. Four patients reported significant improvement, three patients reported mild improvement and two patients reported no appreciable improvement in the Visual Analog Scale (VAS). Two patients who reported no appreciable improvement in VAS also did not achieve FSR. In these patients, calcium hydroxide was spread widely along the IAN and a surgical approach was obtained via sagittal spit osteotomy. The mean time to reach FSR was 222.7 (\u00b141.8)\\xa0days with a range of 106-397\\xa0days. In the early repair group who received surgery within 60\\xa0days, three out of five patients achieved FSR in a mean time of 198.0 (\u00b176.2)\\xa0days. The mean time to FSR in all four subjects who received surgical attention over 60\\xa0days after injury was 241.3 (\u00b1139.8)\\xa0days with a range of 106-397\\xa0days. As all four cases in the late repair group with limited amount of nerve injury achieved FSR, only 3 of 5 early repair cases with wide-spread injury achieved a similar outcome.",
            "output": [
                "Do surgical management of damaged inferior alveolar nerve caused by endodontic overfilling of calcium hydroxide paste?"
            ]
        },
        {
            "id": "task847-b5f5fcbe1f96481fb262c7a377c9d35c",
            "input": "Patient care decisions demand high-quality research. To assist those decisions, numerous observational studies are being performed. Are the standards and guidelines to assess observational studies consistent and actionable? What policy considerations should be considered to ensure decision makers can determine if an observational study is of high-quality and valid to inform treatment decisions?', 'Based on a literature review and input from six experts, we compared and contrasted nine standards/guidelines using 23 methodological elements involved in observational studies (e.g., study protocol, data analysis, and so forth).', 'Fourteen elements (61%) were addressed by at least seven standards/guidelines; 12 of these elements disagreed in the approach. Nine elements (39%) were addressed by six or fewer standards/guidelines. Ten elements (43%) were not actionable in at least one standard/guideline that addressed the element.",
            "output": [
                "Is standards and guidelines for observational studies : quality in the eye of the beholder?"
            ]
        },
        {
            "id": "task847-5c3f7e99b91849f3adfcee0e7aef0401",
            "input": "Isorhamnetin (Isor), a 3-O-methylated metabolite of quercetin, has shown antioxidant and anti-proliferative effects in previous studies. In this study, we investigated the anti-inflammatory effect of Isor on LPS-induced acute lung injury (ALI). Accordingly, we evaluated the effect of Isor on cytokine production elevated by LPS (1\\xa0\u03bcg/ml) in vitro. An in vivo ALI murine model was also established via lipopolysaccharide inhalation (LPS, 20\\xa0mg/kg), and the cytokine levels and inflammatory cell count in bronchoalveolar lavage fluid (BALF) were evaluated. The observed lung injury was assessed using histopathologic sections via H&E straining. Furthermore, to investigate whether the anti-inflammatory effect of Isor is associated with NF-\u03baB and MAPKs pathway activation, the phosphorylated levels of ERK, JNK, I\u03baBa and NF-\u03baB(p65) were determined.', 'Isor significantly inhibited LPS-induced TNF-\u03b1, IL-1\u03b2 and IL-6 secretion both in vitro and in vivo. Neutrophil infiltration and edema in an ALI model were substantially alleviated. The histopathological changes induced by LPS were lessened by Isor. Additionally, Isor notably suppressed the phosphorylation of ERK, JNK, I\u03baBa and NF-\u03baB(p65) activated by LPS in vivo.",
            "output": [
                "Does isorhamnetin protect mice from lipopolysaccharide-induced acute lung injury via the inhibition of inflammatory responses?"
            ]
        },
        {
            "id": "task847-ecdeb444598c46779884269c283b9b9d",
            "input": "Reabsorption of bile acids from the intestine by ileal bile acid transporter is pivotal for the enterohepatic circulation of BAs and sterol homoeostasis.', 'To assess tolerability and study, bile acid metabolism in a phase 1 trial with the selective ileal bile acid transporter inhibitor A4250.', 'A randomised double-blind, single-ascending dose (SAD) and multiple-ascending-dose study consisting of five cohorts comprising 40 individuals with a single administration of A4250 (0.1, 0.3, 1, 3, or 10\\xa0mg) or placebo and three cohorts comprising 24 individuals with a 1-week administration of A4250 (1 or 3\\xa0mg once daily or 1.5\\xa0mg twice daily) or placebo. For the multiple-ascending-dose study, bile acids were measured by HPLC-MS in plasma and faeces, and fibroblast growth factor 19 (FGF19) and 7\u03b1-hydroxy-4-cholesten-3-one (C4) were measured in plasma.', 'No serious adverse events occurred and all participants finished the trial per protocol. At the end of the multiple-ascending-dose study, plasma total bile acids and FGF19 decreased by 47% and 76%, respectively, at 3\\xa0mg/day (P\\xa0<\\xa00.01), and by 15% and 16%, respectively, at 1.5\\xa0mg twice daily (P\\xa0<\\xa00.05). Plasma C4 and faecal bile acids increased at all dose regimens, by 555%, 664%, 292% and 338%, 421%, 420%, respectively (P\\xa0<\\xa00.01-0.05). The primary bile acids cholic and chenodeoxycholic acids constituted the majority of faecal bile acids in the A4250-treated groups.",
            "output": [
                "Does the ileal bile acid transporter inhibitor A4250 decrease serum bile acids by interrupting the enterohepatic circulation?"
            ]
        },
        {
            "id": "task847-6477baccd12148b5a242389c895b55f5",
            "input": "We evaluated conventional ASSR (Bio-logic MASTER II) and NB CE-Chirp ASSR thresholds as objective hearing measures in both normal and hearing loss subjects.', \"Patients with sensorineural hearing loss and volunteer normal hearing subjects were enrolled. Pure tone thresholds at 0.5, 1, 2 and 4 kHz were compared with the corresponding thresholds measured using Bio-logic MASTER II and the Eclipse ASSR systems. The threshold differences and correlation with pure tone were measured and reliability was evaluated with Cronbach's \u03b1. In part I of the study, all subjects were included, in part II of the study, only mild hearing loss and normal hearing subjects were included.\", 'In part I, NB CE-Chirp ASSR revealed a significantly smaller difference in threshold than conventional ASSR, a better correlation and better reliability. However, lower frequencies of NB CE-Chirp tended to be less reliable than higher frequencies. In part II, NB CE-Chirp revealed smaller threshold differences than conventional ASSR. Both correlation scores and reliability values were generally lower in the part II results.",
            "output": [
                "Is narrow band CE-Chirp auditory steady-state response more reliable than the conventional ASSR in predicting the behavioral hearing threshold?"
            ]
        },
        {
            "id": "task847-32687dd9739e47d58a742a9e01e55d6a",
            "input": "Inflammatory risk factors in childhood, e.g. obesity, impact on carotid artery intima media thickness (CIMT), an early indicator of atherosclerosis. Little is known on potential infectious origins in childhood. We investigated the association between number of reported different childhood infectious diseases and CIMT in adolescence.', \"288 SAPALDIA offspring (8-21years) underwent a clinical examination in 2010-2011: anthropometry, blood pressure, CIMT, blood draw (cardiovascular biomarkers, cotinine). Offspring and parents gave information on individuals' and family health, child's vaccination status, infectious diseases and other early life factors. Life-time prevalence of bronchitis, pneumonia, tonsillitis, otitis, mononucleosis, meningitis, appendicitis, and scarlet fever were investigated, separately, and as cumulative infectious disease score. Multilevel adjusted linear regression analysis on the association between subjects' CIMT average and infectious diseases score was performed, stratifying by sex.\", 'Youth (mean age 14.8\\xa0yrs; 53% female) reported on average 1.3 of the listed infectious diseases; 22% boys and 15% girls reported \u22653 infectious diseases (p\\xa0=\\xa00.136). Two-thirds were vaccinated according to recommendations (boys 56%, girls 61.5%, p\\xa0=\\xa00.567). Sex-stratified analyses yielded significantly increased CIMT in boys with \u22653 infectious diseases vs. none (0.046\\xa0mm, 95%CI 0.024; 0.068). In girls, the effect was of same direction but statistically non-significant (0.011\\xa0mm, 95%CI\\xa0-0.015; 0.036).",
            "output": [
                "Are infectious diseases associated with carotid intima media thickness in adolescence?"
            ]
        },
        {
            "id": "task847-34acd96fd1ea4cd4997a480426afbbab",
            "input": "The goal of this study was to establish an apolipoprotein E-deficient (ApoE(-/-)) rat model.', 'The ApoE(-/-) rat was created by TALEN-mediated gene targeting in the genetic background of Sprague Dawley rat. Six-to eight-week-old male rats were used in the experiments (n\\xa0=\\xa010 in each group).', 'After fed with high-cholesterol diet (HCD) for 12 weeks, the ApoE(-/-) rats displayed typical dyslipidemia. In contrast, HCD failed to induce hypercholesterolemia in wild-type rats. However, there was no obvious atherosclerotic lesion in oil red O-stained en face aortas and the aortic root sections in both genetic types of rats. Interestingly, partial ligation caused the formation of plaques consist of lipid and macrophages in carotid arteries from ApoE(-/-) rats, but induced the neointimal hyperplasia in wild-type rats. Additionally, we found that HCD slightly increased the expression of adhesion molecules, while partial ligation dramatically upregulated these molecules.",
            "output": [
                "Do apolipoprotein E-deficient rats develop atherosclerotic plaques in partially ligated carotid arteries?"
            ]
        },
        {
            "id": "task847-f2b0ca08be13439cb2f3e7d500dc403f",
            "input": "Radiation therapy, alone or in combination with chemotherapy, is effective for patients with locally advanced and recurrent pancreatic cancer. Ionizing radiation induces cell cycle arrest and cell apoptosis through enhancement several signals such as p53, p21(Waf1/Cip1), and caspase. However, the therapeutic efficacy is attenuated by radiation-induced activation of NF-\u03baB. Nafamostat mesilate, a synthetic serine protease inhibitor, inhibits NF-\u03baB activation in pancreatic cancer. Therefore, we hypothesized that nafamostat mesilate inhibited radiation-induced activation of NF-\u03baB and improves therapeutic outcome.', 'In combination group, NF-\u03baB activation was significantly inhibited in comparison with that of radiation group. Nafamostat mesilate obviously down-regulated the expression levels of Mdm2 compared with control cells or irradiated cells. Consequently, p53 expression was stabilized inversely in correlation with Mdm2 protein expression level. The expression levels of p53, p21(Waf1/Cip1), cleaved caspase-3 and -8 were the highest in the combination group. Nafamostat mesilate enhanced ionizing radiation-induced cell apoptosis and G2/M cell cycle arrest. In combination group, cell proliferation and tumor growth were significantly slower than those in other groups.",
            "output": [
                "Do dual inhibition of nuclear factor kappa-B and Mdm2 enhance the antitumor effect of radiation therapy for pancreatic cancer?"
            ]
        },
        {
            "id": "task847-159ffe9a7d65444f859cc3dba1522d1c",
            "input": "Apelin plays an important role in the protection against myocardial ischemia-reperfusion (I/R) injury, while the mechanism still remains unclear. In the current study, we aimed to evaluate the protective effect of apelin-13, and the main mechanism.', 'The in vivo I/R injury model (Sprague-Dawley rat) was established, then infarct size, expression levels of phospho-protein kinase B (p-Akt), phospho-extracellular signal-regulated kinase (p-ERK) and phospho-glycogen synthase kinase-3\u03b2 (p-GSK-3\u03b2) were measured. The fluorescence intensity of tetramethylrhodamine ethyl ester perchlorate (TMRE) of the isolated myocardial cells was determined to evaluate the opening of the mitochondrial permeability transition pore (mPTP) caused by oxidant stress and hypoxia/reoxygenation.', 'For the established I/R injury model, apelin-13 and SB216763 (GSK-3\u03b2 inhibitor) significantly reduced the infarct size (p < 0.05), which could be abolished by LY294002 (PI3K inhibitor), PD98059 (MEK inhibitor) and atractyloside (mPTP accelerator). The enhanced expression levels of p-Akt, p-ERK and p-GSK-3\u03b2 caused by apelin-13 (p < 0.05) could be counteracted by LY294002 and PD98059. The reduced fluorescence intensity of TMRE in the H2O2/apelin-13 and H2O2/SB216763 treated groups was significantly lower (p < 0.05), indicating that apelin-13 and SB216763 could reduce the decline in mitochondrial membrane potential caused by oxidant stress, and the fluorescence intensity in the hypoxia/reoxygenation + apelin-13 group was significantly lower (p < 0.05), which suggested that apelin-13 could inhibit the mitochondrial membrane potential changes induced by hypoxia/reoxygenation.",
            "output": [
                "Does apelin-13 protect the heart against ischemia-reperfusion injury through the RISK-GSK-3\u03b2-mPTP pathway?"
            ]
        },
        {
            "id": "task847-2203fee6c1ac431ab1c444696135c454",
            "input": "Readout-segmented echo planar imaging (rs-EPI) significantly reduces susceptibility artifacts in diffusion-weighted imaging (DWI) of the breast compared to single-shot EPI but is limited by longer scan times. To compensate for this, we tested a new simultaneous multi-slice (SMS) acquisition for accelerated rs-EPI.', 'After approval by the local ethics committee, eight healthy female volunteers (age, 38.9 \u00b1 13.1 years) underwent breast MRI at 3T. Conventional as well as two-fold (2\u00d7 SMS) and three-fold (3\u00d7 SMS) slice-accelerated rs-EPI sequences were acquired at b-values of 50 and 800 s/mm(2). Two independent readers analyzed the apparent diffusion coefficient (ADC) in fibroglandular breast parenchyma. The signal-to-noise ratio (SNR) was estimated based on the subtraction method. ADC and SNR were compared between sequences by using the Friedman test.', 'The acquisition time was 4:21 min for conventional rs-EPI, 2:35 min for 2\u00d7 SMS rs-EPI and 1:44 min for 3\u00d7 SMS rs-EPI. ADC values were similar in all sequences (mean values 1.62 \u00d7 10(-3)mm(2)/s, p=0.99). Mean SNR was 27.7-29.6, and no significant differences were found among the sequences (p=0.83).",
            "output": [
                "Do simultaneous multi-slice readout-segmented echo planar imaging for accelerated diffusion-weighted imaging of the breast?"
            ]
        },
        {
            "id": "task847-f3d75d5d8969412fa7d63afa83fc2772",
            "input": "The modifiable variable best proven to improve survival after resection of pancreatic adenocarcinoma is the addition of adjuvant chemotherapy. A theoretical advantage of minimally invasive pancreaticoduodenectomy (MI-PD) is the potential for greater use and earlier initiation of adjuvant therapy, but this benefit remains unproven.', 'The 2010-2012 National Cancer Data Base (NCDB) was queried for patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma. Subjects were classified as MI-PD versus open pancreaticoduodenectomy (O-PD). Baseline variables were compared between groups. The independent effect of surgical approach on the use and timing of adjuvant chemotherapy was estimated using multivariable regression analyses.', 'For this study, 7967 subjects were identified: 1191 MI-PD (14.9%) and 6776 O-PD (85.1%) patients. Patients who underwent MI-PD were more likely to have been treated at academic hospitals. Otherwise, the groups had no baseline differences. In both the MI-PD and O-PD groups, approximately 50% of the patients received adjuvant chemotherapy, initiated at a median of 54 versus 55 days postoperatively (p = 0.08). After multivariable adjustment, surgical approach was not independently associated with use (odds ratio 1.00; p = 0.99) or time to initiation of adjuvant chemotherapy (-2.3 days; p = 0.07). Younger age, insured status, lower comorbidity score, higher tumor stage, and the presence of lymph node metastases were independently associated with the use of adjuvant chemotherapy.",
            "output": [
                "Does minimally Invasive Pancreaticoduodenectomy Improve Use or Time to Initiation of Adjuvant Chemotherapy for Patients With Pancreatic Adenocarcinoma?"
            ]
        },
        {
            "id": "task847-9a555d7f45d443cab87e626fee9d26a4",
            "input": "Notch signaling is indicated as novel therapeutic targets to prevent recurrence of breast cancer. LncRNAs were identified as downstream target of Notch pathway. However, the exact mechanisms involved in Notch signaling, lncRNAs and breast cancer remain to be explained.', 'This original research aimed to determine the prognostic implications of Notch-1 for breast cancer, and explain mechanisms involved in regulation of lnRNA GAS5 by Notch-1, and identify the function of this mechanism on breast cancer.', 'Thirty breast cancer patients were included from The First Affiliated Hospital of Anhui Medical University (China) since January 2006 in this study. The mRNA level by RT-PCR and protein level of Notch-1 by western blot in tumor tissues and adjacent normal tissues were evaluated and 5-year survival analysis was applied to examine the significance of Notch-1. The levels of ten reported lncRNAs were determined by RT-PCR, and subsequently linear analysis was applied to analyze the relationship between these four unique lncRNAs and protein level of Notch-1, which identified the most relevant lncRNA GAS5 with Notch-1 in breast cancer. Subsequently, Notch1-siRNA was applied to influence the expression of Notch-1 in T47D, then the level of RSA5 was measured by RT-PCR, and CCK-8 assay was applied to measure the proliferation of T47D cells.', 'High level of Notch-1 provided a poor prognosis in breast cancer. Interference of Notch-1 significantly suppressed proliferation of T47D cell (P < 0.05), and significantly increased the level of GAS5.",
            "output": [
                "Does notch-1 promote breast cancer cells proliferation by regulating LncRNA GAS5?"
            ]
        },
        {
            "id": "task847-dc7b4447cfdc4678b900a511ba040641",
            "input": "Space-consuming mediastinal tumors can create respiratory failure.', 'We are reporting on a case of mediastinal lymphoma, which created respiratory failure in our patient. IV steroid therapy was used in our patient, who presented with end-stage respiratory failure.', 'Conservative management of our patient was possible without the application of ECMO.",
            "output": [
                "Does steroid treatment resolve acute respiratory failure in patient transferred for ECMO?"
            ]
        },
        {
            "id": "task847-3fcc3ebeebf443f5b15a899c3623c2b4",
            "input": "Neonatal therapy-resistant septic shock is a common problem in middle and low-income countries. We investigated whether newborn infants with infection and therapy-resistant hypotension showed evidence of abnormal levels of cortisol or cortisol precursors.', 'A total of 60 term or near term neonates with evidence of infection were enrolled after informed consent. Of these, 30 had an infection and refractory shock and 30 had an infection without shock. There were no detectable differences between the groups in the length of gestation, birth weight or gender distribution. Serum was obtained during days four and 14 after birth. Cortisol and cortisol precursor concentrations were analysed using liquid chromatography-tandem mass spectrometry.', 'The cortisol concentrations were low considering the expected responses to stress and they did not differ between the groups. The infants with infection and shock had higher serum dehydroepiandrosterone (DHEA) levels than those without shock (319.0 \u00b1 110.3 \u03bcg/dL, versus 22.3 \u00b1 18.3 \u03bcg/dL; p < 0.0001) and they also had higher 17-hydroxy-pregnenolone, pregnenolone and progesterone concentrations. There were no detectable differences in the levels of 17-hydroxy-progesterone, 11-deoxy-cortisol, cortisol or cortisone.",
            "output": [
                "Do term neonates with infection and shock display high cortisol precursors despite low levels of normal cortisol?"
            ]
        },
        {
            "id": "task847-6757b1ecd4454ce192ad554394611001",
            "input": "Progressive loss of skeletal muscle mass with aging (sarcopenia) forms a global health concern. It has been suggested that an impaired capacity to increase muscle protein synthesis rates in response to protein intake is a key contributor to sarcopenia. We assessed whether differences in post-absorptive and/or post-prandial muscle protein synthesis rates exist between large cohorts of healthy young and older men.', 'We performed a cross-sectional, retrospective study comparing in vivo post-absorptive muscle protein synthesis rates determined with stable isotope methodologies between 34 healthy young (22\u00b11 y) and 72 older (75\u00b11 y) men, and post-prandial muscle protein synthesis rates between 35 healthy young (22\u00b11 y) and 40 older (74\u00b11 y) men.', 'Post-absorptive muscle protein synthesis rates did not differ significantly between the young and older group. Post-prandial muscle protein synthesis rates were 16% lower in the older subjects when compared with the young. Muscle protein synthesis rates were >3 fold more responsive to dietary protein ingestion in the young. Irrespective of age, there was a strong negative correlation between post-absorptive muscle protein synthesis rates and the increase in muscle protein synthesis rate following protein ingestion.",
            "output": [
                "Does aging be Accompanied by a Blunted Muscle Protein Synthetic Response to Protein Ingestion?"
            ]
        },
        {
            "id": "task847-32e739b13cd245ccaab98dccccf55936",
            "input": "Bilateral salpingo-oophorectomy (BSO) is a risk factor for osteoporosis. Previous studies have reported an association between genetic polymorphisms and the risk of developing osteoporosis. However, the relationship between osteoporosis and genetic polymorphisms in Japanese women treated with BSO is not well understood. To improve the quality of life for post-BSO patients, it is important to determine the genetic factors that influence their risk for osteoporosis. The aim of this study was to investigate the association between gene variations of estrogen metabolism-related genes and osteoporosis in surgically menopausal patients, which may improve their quality of life.', 'This study included 203 menopausal women treated with BSO because of gynecologic disorders. One hundred and twenty-six women with artificial (surgical) menopause, who had undergone BSO in the premenopausal period, were compared with 77 women with natural menopause, who had undergone BSO in the postmenopausal period. The women were tested for bone mineral density to diagnose osteoporosis. Polymorphisms of estrogen receptor 1 (ESR1) and UDP-glucuronosyl transferase (UGT) genes UGT2B17 and UGT1A1 were analyzed, and their association with bone mass and osteoporosis was statistically evaluated.', 'No significant association was found between osteoporosis and polymorphisms in ESR1, UGT2B17, or UGT1A1 in both groups, suggesting that BSO might be a more significant physiological factor in influencing bone mass density compared to genetic variations.",
            "output": [
                "Are polymorphisms of estrogen metabolism-related genes ESR1 , UGT2B17 , and UGT1A1 associated with osteoporosis in surgically menopausal Japanese women?"
            ]
        },
        {
            "id": "task847-bfaa8f20370d4d9d835df5c0c3bfd5ff",
            "input": "MiRNAs has been shown to be implicated in the pathogenesis of many human diseases including cancer. Dysregulation of miR-744 is common in a number of cancers, indicating miR-774 might be closely correlated with the tumorigenesis process. However, the role and clinical significance of miR-774 in nasopharyngeal carcinoma (NPC) is poorly known. Thus the aim of this study is to investigate whether there was any clinical value of serum miR-744 in detecting and predicting the prognosis of NPC.', 'Real-time PCR was used to examine the expression level of serum miR-744 in patients with NPC and the healthy volunteers. The changes in serum miR-744 expression level of NPC patients after receiving chemo-radiotherapy were also evaluated. The association between pre-treatment serum miR-744 expression level and NPC clinicopathological parameters was investigated. Finally we employed Kaplan-Meier method and Cox proportional hazards model to evaluate the clinical value of serum miR-744 in predicting the prognosis of NPC.', 'Our study showed the expression level of serum miR-744 was significant higher in patients with NPC in comparison with healthy controls (P<0.01). The serum miR-744 expression level was down-regulated significantly in NPC patients after receiving chemo-radiotherapy (P<0.01). The Pre-treatment Serum miR-744 expression level was correlated with various important NPC clinicopathological parameters including N stage, clinical stage and grade. In addition, NPC patients with higher serum miR-744 expression had poorer 5 year overall survival rate and relapse-free survival rate. What was more, serum miR-744 was showed to be an independent factor for predicting the prognosis of NPC.",
            "output": [
                "Does up-regulation of serum miR-744 predict poor prognosis in patients with nasopharyngeal carcinoma?"
            ]
        },
        {
            "id": "task847-7f02ae7206954b59bc665770eb290186",
            "input": "Differentiating bipolar disorder (BD) from major depressive disorder (MDD) often poses a major clinical challenge, and optimal clinical care can be hindered by misdiagnoses. This study investigated the differences between BD and MDD in resting-state functional network connectivity (FNC) using a data-driven image analysis method.', 'In this study, fMRI data were collected from unmedicated subjects including 13 BD, 40 MDD and 33 healthy controls (HC). The FNC was calculated between functional brain networks derived from fMRI using group independent component analysis (ICA). Group comparisons were performed on connectivity strengths and other graph measures of FNC matrices.', 'Statistical tests showed that, compared to MDD, the FNC in BD was characterized by more closely connected and more efficient topological structures as assessed by graph theory. The differences were found at both the whole-brain-level and the functional-network-level in prefrontal networks located in the dorsolateral/ventrolateral prefrontal cortex (DLPFC, VLPFC) and anterior cingulate cortex (ACC). Furthermore, interconnected structures in these networks in both patient groups were negatively associated with symptom severity on depression rating scales.",
            "output": [
                "Does resting-state functional network connectivity in prefrontal regions differ between unmedicated patients with bipolar and major depressive disorders?"
            ]
        },
        {
            "id": "task847-76c2cfd10c4742c188fd65941d38f395",
            "input": "Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. The encoding frequency (ke) maps the measured phase to tissue displacement while the strength of the encoding gradients affects image quality. 2D cine DENSE studies have used a ke of 0.10\\xa0cycles/mm, which is high enough to remove an artifact-generating echo from k-space, provide high sensitivity to tissue displacements, and dephase the blood pool. However, through-plane dephasing can remove the unwanted echo and dephase the blood pool without relying on high ke. Additionally, the high sensitivity comes with the costs of increased phase wrapping and intra-voxel dephasing. We hypothesized that ke below 0.10\\xa0cycles/mm can be used to improve image characteristics and provide accurate measures of cardiac mechanics.', 'Spiral cine DENSE images were obtained for 10 healthy subjects and 10 patients with a history of heart disease on a 3\\xa0T Siemens Trio. A mid-ventricular short-axis image was acquired with different ke: 0.02, 0.04, 0.06, 0.08, and 0.10\\xa0cycles/mm. Peak twist, circumferential strain, and radial strain were compared between acquisitions employing different ke using Bland-Altman analyses and coefficients of variation. The percentage of wrapped pixels in the phase images at end-systole was calculated for each ke. The dephasing of the blood signal and signal to noise ratio (SNR) were also calculated and compared.', 'Negligible differences were seen in strains and twist for all ke between 0.04 and 0.10\\xa0cycles/mm. These differences were of the same magnitude as inter-test differences. Specifically, the acquisitions with 0.04\\xa0cycles/mm accurately quantified cardiac mechanics and had zero phase wrapping. Compared to 0.10\\xa0cycles/mm, the acquisitions with 0.04\\xa0cycles/mm had 9\\xa0% greater SNR and negligible differences in blood pool dephasing.",
            "output": [
                "Does 2D cine DENSE with low encoding frequencies accurately quantify cardiac mechanics with improved image characteristics?"
            ]
        },
        {
            "id": "task847-2a077e17b4e24335a38ef555eead3d0f",
            "input": "Linc00152 has been identified highly associated with the tumorigenesis and development of gastric cancer, however, the detailed mechanism of Linc00152 involved still remains unclear.', 'RT-PCR and western blot were used to detect the expression of Linc00152 and EGFR. The CCK8 and EDU assay was employed to measure cell proliferation while xenotransplantation technology was applied in BALB/C nude mice. The interaction between lncRNA and target protein was investigated by RNA pull-down and RNA immunoprecipitation assay.', 'In this study, we first confirmed the upregulation of cytoplasmic expressed Linc00152 in 72 pair tissues of gastric patients. A suppression of cell proliferation and tumor growth was obtained in MGC803 and HGC-27 cells treated with Linc00152 shRNA. RNA pull-down and RIP assay revealed that Linc00152 could directly bind with EGFR which caused an activation of PI3K/AKT signaling.",
            "output": [
                "Does linc00152 promote proliferation in gastric cancer through the EGFR-dependent pathway?"
            ]
        },
        {
            "id": "task847-e043a67465214a1594c2871bf99ac2b3",
            "input": "To test the effects of a novel Mn porphyrin oxidative stress modifier, Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE), for its radioprotective and radiosensitizing properties in normal tissue versus tumor, respectively.', 'Murine oral mucosa and salivary glands were treated with a range of radiation doses with or without MnBuOE to establish the dose-effect curves for mucositis and xerostomia. Radiation injury was quantified by intravital near-infrared imaging of cathepsin activity, assessment of salivation, and histologic analysis. To evaluate effects of MnBuOE on the tumor radiation response, we administered the drug as an adjuvant to fractionated radiation of FaDu xenografts. Again, a range of radiation therapy (RT) doses was administered to establish the radiation dose-effect curve. The 50% tumor control dose values with or without MnBuOE and dose-modifying factor were determined.', 'MnBuOE protected normal tissue by reducing RT-mediated mucositis, xerostomia, and fibrosis. The dose-modifying factor for protection against xerostomia was 0.77. In contrast, MnBuOE increased tumor local control rates compared with controls. The dose-modifying factor, based on the ratio of 50% tumor control dose values, was 1.3. Immunohistochemistry showed that MnBuOE-treated tumors exhibited a significant influx of M1 tumor-associated macrophages, which provides mechanistic insight into its radiosensitizing effects in tumors.",
            "output": [
                "Does novel Manganese-Porphyrin Superoxide Dismutase-Mimetic widen the Therapeutic Margin in a Preclinical Head and Neck Cancer Model?"
            ]
        },
        {
            "id": "task847-edad98118aac4d13af7437ac0b29ce2c",
            "input": "Recent studies have reported the association of gamma-glutamyltransferase (GGT) or ferritin with metabolic disorders. However, there has been no large population-based study assessing the interrelationship of these two biomarkers and their association with insulin resistance.', \"A population-based cross-sectional study was carried out in the Chinese Liangshan Yi ethnic group. 756 eligible subjects, aged 20 - 74 years, were included. Demographic characteristics, medical history, and lifestyle data were collected through questionnaires. An oral glucose tolerance test was performed. Laboratory tests, including GGT and ferritin measurements, were conducted. Spearman's rank-order correlation and multiple linear regression were used to calculate the correlation of GGT with ferritin and their relationship to the insulin resistance index determined by the homeostasis model assessment (HOMA-IR).\", 'A significant correlation between serum GGT and ferritin levels was found (r = 0.393, p < 0.05). GGT was independently correlated with ferritin after adjustment for age, gender, place of residence, education, income, leisure-time physical activity, drinking, smoking, body mass index, systolic pressure, diastolic pressure, hepatitis B surface antigen, anti-hepatitis C virus, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, triglyceride, high density lipoprotein-cholesterol, fasting plasma glucose, 2-hour postprandial plasma glucose, uric acid, and urinary albumin to creatinine ratio (p < 0.05). Positive correlations were established between HOMA-IR and GGT (standard \u03b2 = 0.252) or ferritin (standard \u03b2 = 0.181) after adjustment for multiple confounders (p < 0.05).",
            "output": [
                "Are serum Gamma-Glutamyltransferase and Ferritin Related to Insulin Resistance : A Population-Based Study?"
            ]
        },
        {
            "id": "task847-f64ce94c82034708842110a11dbaf6b3",
            "input": "the study was aimed at assessment of the efficacy of percutaneous high frequency selective rhizotomy (PHFSR) after failure of conservative treatment of trigeminal neuralgia (TN) in multiple sclerosis (MS).', \"A retrospective analysis of 28 patients with TN associated with MS who underwent percutaneous rhizotomy in the period from 2000 to 2014 was performed. All patients were definitely diagnosed with MS according to the McDonald criteria (version of 2001, 2005, and 2010). The patients were divided by age, gender, and the trigeminal nerve branches involved in the process. The patients' condition was evaluated at different times after surgery.\", 'Good outcomes in the form of pain syndrome regression were achieved in 100% of the patients. A disease recurrence was observed in 6 (21%) patients during a follow-up period of 3 months to 14 years. Dysesthesia complications occurred in 4 (14%) patients. There were no deaths and severe complications. The percentage of minor complications was low.",
            "output": [
                "Do [ Experience in the use of high-frequency selective percutaneous rhizotomy in trigeminal neuralgia associated with multiple sclerosis ]?"
            ]
        },
        {
            "id": "task847-4a0d0f1563224dc58513ad2d2fcf30d5",
            "input": "Falls from heights are the most common traumatic event associated with emergency department visits in children. This study investigated the incidence and clinical course of cranial neuropathies caused by falls from heights in children.', 'The computerized records of a tertiary pediatric medical center were searched for all patients admitted to the emergency department in 2004-2014 with a head injury caused by falling from a height. Those with cranial neuropathies involving optic and eye-motility disturbances were identified, and their clinical, imaging, and outcome data were evaluated.', 'Of the estimated 61,968 patients who presented to the emergency department during the study period because of a fall, 18,758 (30.3\\xa0%) had head trauma. Only 12 (seven boys, five girls, average age 6.7\\xa0years) had a visual disturbance. Eight were diagnosed with traumatic optic neuropathy, one after a 6-month delay, including two with accompanying cranial nerve (CN) III injuries. Five patients had anisocoria or an abnormal pupillary response to light at presentation, one patient had CN VI paralysis and temporary vision loss, and one patient had an isolated CN III injury diagnosed on follow-up. Visual improvement varied among the patients.",
            "output": [
                "Does severe cranial neuropathies caused by fall from heights in children?"
            ]
        },
        {
            "id": "task847-a2f1904793f24f99927a9bd32fecb2be",
            "input": "An intricate gene regulatory network drives neural crest migration and differentiation. How epigenetic regulators contribute to this process is just starting to be understood.', 'We found that mutation of med14 or brg1 in zebrafish embryos resulted in a cluster of neural crest cell-related defects. In med14 or brg1 mutants, neural crest cells that form the jaw skeleton were specified normally and migrated to target sites. However, defects in their subsequent terminal differentiation were evident. Transplantation experiments demonstrated that med14 and brg1 are required directly in neural crest cells. Analysis of med14; brg1 double mutant embryos suggested the existence of a strong genetic interaction between members of the Mediator and BAF complexes.",
            "output": [
                "Does med14 cooperate with brg1 in the differentiation of skeletogenic neural crest?"
            ]
        },
        {
            "id": "task847-2fe2e6fff66a44c4b43ec1c4cab38d8c",
            "input": "To explore the impact of titanium implant on the growth and development of pediatric mandible after suffering from mandibular fracture and undergoing open reduction and internal fixation (ORIF) compared with those that underwent titanium plate removal postoperatively.', \"Fifteen pediatric patients with mandibular fracture who underwent ORIF were included in this study. Eight patients did not undergo titanium implant removal postoperatively, whereas the other seven patients underwent the routine. The postoperative data of the pediatrics were collected for comparative analysis by taking the patients' frontal and lateral photos, recording the inter-incisor distance, and measuring the height of mandibular ramus, length of the mandibular body, and combined length of the mandible in three-dimensional reconstruction image.\", 'All patients had acceptable facial contour, mouth opening, and occlusion, without obvious abnormalities. The radiography showed no significant difference between the bilateral mandibular lengths in the two groups of patients (P>0.05).",
            "output": [
                "Do [ Long-term follow-up study of titanium implant impact on pediatric mandibular growth and development ]?"
            ]
        },
        {
            "id": "task847-da9ab2bdfa4a4124bf61c8dd1ddb09bc",
            "input": "Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation. AD is triggered by oxidative stress and immune imbalance. The effect of oral arjunolic acid (AA) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice was investigated.', 'Repeated epicutaneous application of DNCB to the ear and shaved dorsal skin of mice was performed to induce AD-like symptoms and skin lesions: 250mg/kg AA was given orally for three weeks to assess its anti-pruritic effects. Serum levels of tumor necrosis factor (TNF)-\u03b1, interleukin (IL)-4, IL-6, IL-10, immunoglobulin (Ig)E and caspase-3 were assessed by ELISA.', 'We found that AA alleviated DNCB-induced AD-like symptoms as quantified by skin lesions, dermatitis score, ear thickness and scratching behavior. Levels of reactive oxygen species in the AA group were significantly inhibited compared with those in the DNCB group. In parallel, AA blocked a DNCB-induced reduction in serum levels of IL-4 and IL-10 associated with an attenuation of DNCB-induced increases in serum TNF-\u03b1, IL-6, IgE and caspase-3.",
            "output": [
                "Does arjunolic acid protect against DNCB-induced atopic dermatitis-like symptoms in mice by restoring a normal cytokine balance?"
            ]
        },
        {
            "id": "task847-53ecf638449b4c45b4fc7bf2d793893d",
            "input": "Thromboxane A2 (TXA2) can induce the platelet aggregation and lead to thrombosis. This will cause the low-reflow phenomenon after ischemic stroke and aggravate the damage of brain issues. Therefore, it is potential to develop the drugs inhibiting TXA2 pathway to treat cerebral ischemia.', 'This study aims to prove the protective effect of N2 (4-(2-(1H-imidazol-1-yl) ethoxy)-3-methoxybenzoic acid) on focal cerebral ischemia and reperfusion injury through platelet aggregation inhibition.', 'Middle cerebral artery occlusion/reperfusion (MCAO/R) is used as the animal model. Neurological deficit score, Morris water maze, postural reflex test, Limb-use asymmetry test, infarct volume, and water content were performed to evaluate the protective effect of N2 in MCAO/R rats. 9, 11-dieoxy-11\u03b1, 9\u03b1-methanoepoxyprostaglandin F2\u03b1 (U46619) or adenosine diphosphate (ADP) was used as the inducer of platelet aggregation.",
            "output": [
                "Does n2 extenuate experimental ischemic stroke through platelet aggregation inhibition?"
            ]
        },
        {
            "id": "task847-9a6c968dd22a442b8094c6994336c47e",
            "input": "To investigate the DNA-methylation levels in the newly described MEG8 differentially methylated region (DMR) in the imprinted cluster in 14q32 in patients with Temple syndrome.', 'We included three patients with Temple syndrome which were studied by Infinium HumanMethylation450 BeadChips, locus-specific bisulfite-pyrosequencing, methylation-specific-MLPA and microsatellite analyses. The tag-CpG of the MEG8-DMR was investigated using the Infinium HumanMethylation450 BeadChip.', 'In all three patients, the identical pattern of DNA-hypermethylation of the MEG8-DMR was observed along with DNA-hypomethylation of the IG-DMR and MEG3-DMR.",
            "output": [
                "Is the differentially methylated region of MEG8 hypermethylated in patients with Temple syndrome?"
            ]
        },
        {
            "id": "task847-c4dde71721ea4d62aa861ef47a8fd082",
            "input": "Efficient enzymatic saccharification of plant cell wall material is key to industrial processing of agricultural and forestry waste such as straw and wood chips into fuels and chemicals.', \"Saccharification assays were performed on steam-pretreated wheat straw under ambient and O2-deprived environments and in the absence and presence of a lytic polysaccharide monooxygenase (LPMO) and catalase. A kinetic model was used to calculate catalytic rate and first-order inactivation rate constants of the cellulases from reaction progress curves. The addition of a LPMO significantly (P\\xa0<\\xa00.01, Student's T test) enhanced the rate of glucose release from 2.8 to 6.9\\xa0h(-1) under ambient O2 conditions. However, this also significantly (P\\xa0<\\xa00.01, Student's T test) increased the rate of inactivation of the enzyme mixture, thereby reducing the performance half-life from 65 to 35\\xa0h. Decreasing O2 levels or, strikingly, the addition of catalase significantly reduced (P\\xa0<\\xa00.01, Student's T test) enzyme inactivation and, as a consequence, higher efficiency of the cellulolytic enzyme cocktail was achieved.",
            "output": [
                "Does catalase improve saccharification of lignocellulose by reducing lytic polysaccharide monooxygenase-associated enzyme inactivation?"
            ]
        },
        {
            "id": "task847-f0561200f7e245428b8d8f5ee82dff60",
            "input": "Living a purposeful life is associated with better mental and physical health, including longevity. Accumulating evidence shows that these associations might be explained by the association between life purpose and regulation of physiological systems involved in the stress response. The aim of this study was to investigate the prospective associations between life purpose and allostatic load over a 10-year period.', 'Analyses were conducted using data from the Midlife in the United States (MIDUS) survey. Assessment of life purpose, psychological covariates and demographics were obtained at baseline, while biomarkers of allostatic load were assessed at the 10-year follow-up.', 'We found that greater life purpose predicted lower levels of allostatic load at follow-up, even when controlling for other aspects of psychological well-being potentially associated with allostatic load. Further, life purpose was also a strong predictor of individual differences in self-health locus of control-i.e., beliefs about how much influence individuals can exert on their own health-which, in turn, partially mediated the association between purpose and allostatic load. Although life purpose was also negatively linked to other-health locus of control-i.e., the extent to which individuals believe their health is controlled by others/chance-this association did not mediate the impact of life purpose on allostatic load.",
            "output": [
                "Does purpose in life predict allostatic load ten years later?"
            ]
        },
        {
            "id": "task847-3d2cfbbc29cb457db591db285ed22702",
            "input": "Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk variants have a relatively modest effect on risk and show limited potential for predicting FBC development. As an alternative, we hypothesized that additional genomic data types, such as gene-expression levels, which can reflect genetic and epigenetic variation, could contribute to classifying a person's risk status. Specifically, we aimed to identify common patterns in gene-expression levels across individuals who develop FBC.\", 'We profiled peripheral blood mononuclear cells from women with a family history of breast cancer (with or without a germline BRCA1/2 variant) and from controls. We used the support vector machines algorithm to differentiate between patients who developed FBC and those who did not. Our study used two independent datasets, a training set of 124 women from Utah (USA) and an external validation (test) set from Ontario (Canada) of 73 women (197 total). We controlled for expression variation associated with clinical, demographic, and treatment variables as well as lymphocyte markers.', 'Our multigene biomarker provided accurate, individual-level estimates of FBC occurrence for the Utah cohort (AUC = 0.76 [0.67-84]) . Even at their lower confidence bounds, these accuracy estimates meet or exceed estimates from alternative approaches. Our Ontario cohort resulted in similarly high levels of accuracy (AUC = 0.73 [0.59-0.86]), thus providing external validation of our findings. Individuals deemed to have \"high\" risk by our model would have an estimated 2.4 times greater odds of developing familial breast cancer than individuals deemed to have \"low\" risk.",
            "output": [
                "Do gene-expression patterns in peripheral blood classify familial breast cancer susceptibility?"
            ]
        },
        {
            "id": "task847-e99ad6ffb2ff44f9b21ae8a48fb07303",
            "input": "The purpose of this study was to investigate the relation between preoperative chronic cerebral ischemia and postoperative new cerebral ischemia in patients undergoing carotid endarterectomy (CEA).', 'We reviewed the diffusion weighted magnetic resonance images (DWI) of the 51 patients (37 men, mean age 68.8\\u2009\u00b1\\u20098.4 years) undergoing isolated CEA in the preoperative and early postoperative period. The number, anatomic location and the size of new ischemic lesions were recorded.', 'In the preoperative period, 28 (54.9 %) patients were symptomatic. There was chronic cerebral infarction in the preoperative DWI images of 17 patients (33.3 %). In the postoperative period, there was newly developed cerebral ischemia in postoperative DWI images of eight (15.7 %) patients. Six of the eight patients with newly developed cerebral ischemia had chronic cerebral infarction in their preoperative DWI images. The incidence of newly developed cerebral ischemia after CEA in patients with preoperative chronic cerebral ischemia was significantly higher than the incidence in patients without preoperative chronic cerebral ischemia (p\\u2009=\\u20090.01).",
            "output": [
                "Is previous chronic cerebral infarction predictive for new cerebral ischemia after carotid endarterectomy?"
            ]
        },
        {
            "id": "task847-2bc6cdd6b7324954b4decdda9dbba767",
            "input": "MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms.', 'We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting.', 'miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45\u03b1 down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45\u03b1 expression in a xenograft model. Consistently, the knockdown of GADD45\u03b1 expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45\u03b1 mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways.",
            "output": [
                "Does miR-362-5p promote the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45\u03b1?"
            ]
        },
        {
            "id": "task847-4f0e0dffc03e4ed9b709443316b56bde",
            "input": "The CLDN14 gene encodes a protein involved in the regulation of paracellular permeability or ion transport at epithelial tight junctions as in the nephron. The C allele of the rs219780 SNP (single nucleotide polymorphism) of CLDN14 has been associated with renal lithiasis, high levels of parathormone (PTH), and with low bone mineral density (BMD) in healthy women. Our aim is to study the relationship between rs219780 SNP of CLDN14 and renal lithiasis, fractures, and BMD in patients with primary hyperparathyroidism (PHPT).', 'We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analysed anthropometric data, history of fractures or kidney stones, biochemical parameters including markers for bone remodelling, abdominal ultrasound, and BMD and genotyping for the rs219780 SNP of CLDN14.', 'We did not find any difference in the frequency of fractures or renal lithiasis between the genotype groups in PHPT patients. Moreover, we did not find any relationship between the T or C alleles and BMD or biochemical parameters.",
            "output": [
                "Is rs219780 SNP of Claudin 14 Gene Related to Clinical Expression in Primary Hyperparathyroidism?"
            ]
        },
        {
            "id": "task847-b2f3dc2feabd4b08aaae51d7a2b7e214",
            "input": "MicroRNAs are small, single-stranded, non-protein-coding RNAs of about 22 nucleotides. MicroRNA molecules have been identified to play key roles in a broad range of physiologic and pathologic processes. Polymorphisms in the corresponding sequence space are likely to make a significant contribution to phenotypic variation. A T/C genetic variant (rs11614913) in the pre-miR-196a2 sequence could alter mature miR-196a expression and target mRNA binding. The aim of the present study is to evaluate the relationship between this polymorphism and atrial fibrillation (AF).', 'A total of 123 participants were enrolled, 65 AF patients were confirmed with electrocardiogram (ECG) or dynamic electrocardiography, 58 normal individuals were assigned to the control group. Genotypes of the premiR-196a2 were distinguished using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.', 'The distribution of the pre-miR-196a2 genotypes (TT, TC, and CC) was 15.38%, 46.15%, and 38.46% in the AF group and 39.66%, 46.55%, and 13.79% in the controls, respectively (p = 0.0011). Compared with the TT genotype, the C allele carriers (TC+CC genotypes) had a 3.968-fold increased risk of AF (adjusted OR = 3.968, 95% CI = 1.633 - 9.644, p = 0.002). AF patients with the TC+CC genotype had greater left atrial dimension than did patients with the TT genotype (42.10 \u00b1 8.74 vs. 35.13 \u00b1 8.16, p = 0.0224).",
            "output": [
                "Is a Functional Single-Nucleotide Polymorphism in Pre-microRNA-196a2 Associated with Atrial Fibrillation in Han Chinese?"
            ]
        },
        {
            "id": "task847-14f50b8cc82445f6be3d234573cca517",
            "input": "This study assessed the association between first-trimester abdominal adiposity and dysglycemia and gestational diabetes mellitus (GDM) in midpregnancy.', \"In a prospective cohort of 485 women, we measured subcutaneous (SAT), visceral (VAT), and total (TAT) adipose tissue depth, using ultrasound at 11-14 weeks' gestation. Logistic regression analysis assessed the relation between quartiles of SAT, VAT, or TAT depth and the composite outcome of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or GDM, based on a 75-g oral glucose tolerance test at 24-28 weeks.\", 'Adjusting for maternal age, ethnicity, family history of diabetes, and BMI, quartile 4 versus quartile 1 VAT (adjusted odds ratio [aOR] 3.1, 95% CI 1.1-9.5) and TAT (aOR 2.7, 95% CI 1.1-7.8) were significantly associated with the composite outcome, but SAT was not (aOR 1.8, 95% CI 0.70-4.8). The same was seen for GDM alone.",
            "output": [
                "Does first-Trimester Maternal Abdominal Adiposity predict Dysglycemia and Gestational Diabetes Mellitus in Midpregnancy?"
            ]
        },
        {
            "id": "task847-16e06986cd894c07918e826bef157e72",
            "input": "A hexanucleotide expansion in C9orf72 is the major genetic cause of inherited behavioural variant Frontotemporal dementia (bvFTD) and motor neurone disease (MND), although the pathological mechanism(s) underlying disease remains uncertain.', 'Using antibodies to poly-GA, poly-GP, poly-GR, poly-AP and poly-PR proteins, we examined sections of cerebral cortex, hippocampus, thalamus, cerebellum and spinal cord, from 20 patients with bvFTD and/or MND bearing an expansion in C9orf72 for aggregated deposits of dipeptide repeat proteins (DPR).', \"Antibodies to poly-GA, poly-GP and poly-GR detected numerous rounded cytoplasmic inclusions (NCI) within granule cells of hippocampal dentate gyrus and those of the cerebellum, as well as 'star-burst' shaped NCI in pyramidal neurones of CA3/4 region of hippocampus. NCI were uncommon in Purkinje cells, and only very rarely seen in anterior horn cells. Poly-PA antibody detected occasional NCI within CA3/4 neurones alone, whereas poly-PR antibody did not identify any NCI but immunostained the nucleus of anterior horn cells, CA3/4 neurones and Purkinje cells, in patients with or without expansion in C9orf72, as well as in normal controls. Poly-GA antibody generally detected more DPR than poly-GP, which in turn was greater than poly-GR. All patients with bvFTD + MND or MND showed plentiful p62/TDP-43 positive inclusions in remaining anterior horn cells.",
            "output": [
                "Is neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9orf72 linked to TDP-43 pathology and not associated with aggregated forms of dipeptide repeat proteins?"
            ]
        },
        {
            "id": "task847-e61cd4fbf991444a93e06f0af7744dbf",
            "input": "In the past, cervical cancer has been linked to Human Papilloma Virus (HPV) infection. Previously, we found that pre-neoplastic breast and ovarian lesions may be associated with lamin A/C deficiency, resulting in abnormal nuclear morphologies and chromosomal instability. Ultimately, these phenomena are thought to lead to cancer. Here, we assessed lamin A/C deficiency as an indicator for the risk to develop cervical cancer.', 'The expression of lamin A/C was assessed by Western blotting in cervical uterine smears (CUS) of 76 adult women from Benin concomitant with nuclear morphology assessment and HPV genotyping using microscopy and PCR-based assays, respectively. In vitro analyses were performed to uncover the mechanism underlying lamin A/C expression alterations observed in vivo. The presence of cervical intra-epithelial neoplasia (CIN) was assessed by colposcopy.', 'Normal lamin A/C expression (group A) was observed in 39% of the CUS, weak lamin A/C expression (group B) was observed in 28% of the CUS and no lamin A/C expression (group C) was observed in 33% of the CUS tested. Infection with oncogenic HPV was found to be significantly higher in group C (36%) than in groups A (17%) and B (14%). Two years after our first assessment, CIN was observed in 20% of the women in group C. The in vitro application of either a histone deacetylase inhibitor (trichostatin) or a protein kinase inhibitor (staurosporine) was found to restore lamin A/C expression in cervical cancer-derived cells.",
            "output": [
                "Is lamin A/C deficiency an independent risk factor for cervical cancer?"
            ]
        },
        {
            "id": "task847-060f1376e9da4641b0c5a0dc2dae9420",
            "input": "An effective HIV vaccine will likely require induction of both mucosal and systemic cellular and humoral immune responses. We investigated whether intramuscular (IM) delivery of electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal (IN) and IM routes could be combined to induce mucosal and systemic cellular and humoral immune responses to a model HIV-1 CN54 gp140 antigen in mice.', 'Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic or mucosal IgA responses. Cellular IFN\u03b3 responses were preserved in co-immunisation protocols compared to protein-only vaccination groups. The addition of DNA to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein induced expression of cytokines that promote B-cell function, generation of TFH cells and CCR5 ligands that can reduce HIV infectivity.",
            "output": [
                "Does plasmid DNA Vaccine Co-Immunisation modulate Cellular and Humoral Immune Responses Induced by Intranasal Inoculation in Mice?"
            ]
        },
        {
            "id": "task847-0ad142d1b1af418a9d1a0aaa65670b36",
            "input": "To test the hypothesis that individuals who are active but who decrease physical activity (PA) over time have a higher risk of becoming obese in young adulthood, when compared to individuals who are consistently active throughout childhood and adolescence.', 'Iowa Bone Development Study cohort members (242 males and 251 females) participated in accelerometry assessments, dual-energy X-ray absorptiometry scans, and dietary questionnaire surveys at ages 5, 8, 11, 13, 15, 17, and 19 years. Group-based trajectory analyses identified distinct trajectory patterns of moderate- to vigorous-intensity PA (MVPA), percentage of body fat, and energy intake. A multivariable logistic regression model was fit to estimate the odds of \"becoming obese\" based on the MVPA trajectories, adjusted for mother\\'s education, somatic maturation, and energy intake.', 'Among males, 74.7% had a \"normal\" body fat pattern, 14.6% had a \"becoming obese\" pattern, and 10.7% had a \"consistently obese\" pattern, while among females, the percentages were 58.6%, 28.6%, and 12.8%, respectively. Participants who were active (\u226545 min MVPA) as children but decreased MVPA with age were more likely to become obese, compared to consistently active participants (adjusted OR\\u2009=\\u20092.77; 95% CI\\u2009=\\u20091.16, 6.58).",
            "output": [
                "Does active lifestyle in childhood and adolescence prevent obesity development in young adulthood?"
            ]
        },
        {
            "id": "task847-3a37f65e522a4a2f86ac24163cb02969",
            "input": "Bone marrow stromal cell antigen 2 (BST2), also known as tetherin, HM1.24 or CD317 represents a type 2 integral membrane protein, which has been described to restrict the production of some enveloped viruses by inhibiting the virus release from the cell surface. This innate antiviral mechanism is counteracted by the HIV-1 viral factor Vpu, targeting BST2 for cellular degradation. Since antiviral BST2 activity has been mainly confirmed by in vitro data, we investigated its role in vivo on the disease progression using the SIV/macaque model for AIDS. We determined BST2 expression in PBMC and leukocyte subsets of uninfected and SIV-infected rhesus macaques by real-time PCR and flow cytometry and correlated it with disease progression and viral load.', 'Compared to pre-infection levels, we found increased BST2 expression in PBMC, purified CD4(+) lymphocytes and CD14(+) monocytes of SIV-infected animals, which correlated with viral load. Highest BST2 levels were found in progressors and lowest levels comparable to uninfected macaques were observed in long-term non-progressors (LTNPs). During acute viremia, BST2 mRNA increased in parallel with MX1, a prototype interferon-stimulated gene. This association was maintained during the whole disease course.",
            "output": [
                "Is increased BST2 expression during simian immunodeficiency virus infection a determinant of disease progression in rhesus monkeys?"
            ]
        },
        {
            "id": "task847-32d1e933df964dd3aed1490b0b71266d",
            "input": "To prospectively investigate the presence and counts of archaea in feces of 472 children in association with weight development from 6 to 10\\xa0years of age.', 'Within the KOALA Birth Cohort Study, a single fecal sample from each child was analyzed by quantitative polymerase chain reaction to quantify archaea (Methanobrevibacter smithii, Methanosphera stadtmanae). Anthropometric outcomes (overweight [body mass index {BMI}\\xa0\u2265\\xa085th percentile], age- and sex-standardized BMI, weight, and height z-scores) were repeatedly measured at ages (mean\\xa0\u00b1\\xa0SD) of 6.2\\xa0\u00b1\\xa00.5, 6.8\\xa0\u00b1\\xa00.5, 7.8\\xa0\u00b1\\xa00.5, and 8.8\\xa0\u00b1\\xa00.5\\xa0years. Generalized estimating equation was used for statistical analysis while controlling for confounders.', 'Methanobrevibacter smithii colonization was associated with an increased risk of overweight (adjusted odds ratio [OR]\\xa0=\\xa02.69; 95% confidence interval [CI] 0.96-7.54) from 6 to 10\\xa0years of age. Children with high levels (>7 log10 copies/g feces) of this archaeon were at highest risk for overweight (OR\\xa0=\\xa03.27; 95% CI 1.09-9.83). Moreover, M. smithii colonization was associated with higher weight z-scores (adj. \u03b2 0.18; 95% CI 0.00-0.36), but not with height. For BMI z-scores, the interaction (P\\xa0=\\xa00.008) between M. smithii and age was statistically significant, implying children colonized with M. smithii had increasing BMI z-scores with age.",
            "output": [
                "Is gut colonization with methanobrevibacter smithii associated with childhood weight development?"
            ]
        },
        {
            "id": "task847-6ab7ff38178b4033b14ea7e4bc2f18eb",
            "input": "Evidence of attack-related cognitive dysfunction in migraine is growing. Controversy exists on whether cognitive dysfunction, mainly executive, may persist between attacks. Measuring the impact of cognitive function is gaining importance in clinical and research settings in migraine.', 'To compare the performance of interictal migraine patients to controls in an assembled neuropsychological battery focused on executive functions and to study the practice effect of its repeated applications.', 'Assembly of the battery that was then applied twice within 6\\xa0weeks to interictal migraineurs and matched healthy controls.', 'Migraine patients (n\\xa0=\\xa024) and controls (n\\xa0=\\xa024) had similar performance in both applications of the battery. There was a slight practice effect between the first and second evaluation, significant in Stroop Interference test (P\\xa0=\\xa00.002, multiplicity corrected); a meaningful score change was determined for each raw test scores.",
            "output": [
                "Is sequential brief neuropsychological evaluation of migraineurs identical to controls?"
            ]
        },
        {
            "id": "task847-38a38cc485854e3baa949e04b6f9e0d0",
            "input": "Cells detect and adapt to hypoxic and nutritional stress through immediate transcriptional, translational and metabolic responses. The environmental effects of ischemia on chromatin nanostructure were investigated using single molecule localization microscopy of DNA binding dyes and of acetylated histones, by the sensitivity of chromatin to digestion with DNAseI, and by fluorescence recovery after photobleaching (FRAP) of core and linker histones.', 'Short-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40-700 nm in dimension. The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells. The compacted state of chromatin reduces transcription, while the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Digestion of chromatin with DNAseI confirms that oxygen and nutrient deprivation induces compaction of chromatin. Chromatin compaction is associated with depletion of ATP and redistribution of the polyamine pool into the nucleus. FRAP demonstrates that core histones are not displaced from compacted chromatin; however, the mobility of linker histone H1 is considerably reduced, to an extent that far exceeds the difference in histone H1 mobility between heterochromatin and euchromatin.",
            "output": [
                "Does a transient ischemic environment induce reversible compaction of chromatin?"
            ]
        },
        {
            "id": "task847-da25620a9e234859b4335e59e07952da",
            "input": "Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor \u03baB (NF\u03baB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NF\u03baB pathway at very high doses. Whether ASA prodrugs can inhibit NF\u03baB signaling remains relatively unexplored.', 'A library of ASA prodrugs was synthesized and screened for inhibition of NF\u03baB activity and cancer stem-like cell (CSC) properties, an important PGE2-and NF\u03baB-dependent phenotype of aggressive breast cancers. Inhibition of NF\u03baB activity was determined by dual luciferase assay, RT-QPCR, p65 DNA binding activity and Western blots. Inhibition of CSC properties was determined by mammosphere growth, CD44(+)CD24(-)immunophenotype and tumorigenicity at limiting dilution.', 'While we identified multiple ASA prodrugs that are capable of inhibiting the NF\u03baB pathway, several were associated with cytotoxicity. Of particular interest was GTCpFE, an ASA prodrug with fumarate as the ancillary pharmacophore. This prodrug potently inhibits NF\u03baB activity without innate cytotoxicity. In addition, GTCpFE exhibited selective anti-CSC activity by reducing mammosphere growth and the CD44(+)CD24(-)immunophenotype. Moreover, GTCpFE pre-treated cells were less tumorigenic and, when tumors did form, latency was increased and growth rate was reduced. Structure-activity relationships for GTCpFE indicate that fumarate, within the context of an ASA prodrug, is essential for anti-NF\u03baB activity, whereas both the ASA and fumarate moieties contributed to attenuated mammosphere growth.",
            "output": [
                "Does a novel aspirin prodrug inhibit NF\u03baB activity and breast cancer stem cell properties?"
            ]
        },
        {
            "id": "task847-7fdf274ca0b84d3482dec9cf628c2936",
            "input": "The present studies were designed to test the hypothesis that canonical transient receptor potential channel 1 (TRPC1) is required for the proliferation of cochlear spiral ganglion stem/progenitor cells (SPCs).', 'TRPC1 were detected and evaluated in postnatal day 1 CBA/CaJ mice pups derived-cochlear spiral ganglion SPCs by reverse transcription-polymerase chain reaction, Western blot, immunocytochemistry, and calcium imaging. The cell viability and proliferation of the spiral ganglion SPCs following si-RNA mediated knockdown of TRPC1 or addition of TRPC channel blocker SKF9635 were compared to controls.', 'In spiral ganglion SPCs, TRPC1 was found to be the most abundantly expressed TRPC subunit and shown to contribute to store-operated calcium entry. Silencing of TRPC1 or addition of TRPC channel blockers significantly decreased the rate of cell proliferation.",
            "output": [
                "Is tRPC1 required for survival and proliferation of cochlear spiral ganglion stem/progenitor cells?"
            ]
        },
        {
            "id": "task847-a16b7ac5fa2d4c8ea628d79ceaa9e25c",
            "input": "Reagent strip testing for microhaematuria has long been used for community diagnosis of Schistosoma haematobium. Sensitivities and specificities are reasonable, and hence, microhaematuria can serve as a proxy for S. haematobium infection. However, assessment of test performance in the context of the underlying S. haematobium prevalence is rare and test parameters other than sensitivity and specificity have been neglected.', 'Data about the association between microhaematuria and urine filtration results from three studies were compared and put into context with findings from a recent Cochrane review. Data were stratified by S. haematobium prevalence to identify prevalence-related differences in test performance. Kappa agreement and regression models were employed to compare data for different S. haematobium prevalence categories.', 'We found a \"background\" prevalence of microhaematuria (13\\xa0%, on average) which does not seem to be associated with schistosomiasis in most settings, irrespective of the prevalence of S. haematobium. This background level of microhaematuria might be due to cases missed with urine filtration, or alternative causes apart from S. haematobium. Especially in very-low prevalence settings, positive results for microhaematuria likely give an inaccurate picture of the extent of S. haematobium, whereas negative results are a sound indicator for the absence of infection.",
            "output": [
                "Is all that blood is not schistosomiasis : experiences with reagent strip testing for urogenital schistosomiasis with special consideration to very-low prevalence settings?"
            ]
        },
        {
            "id": "task847-e43dc0ffeabc435881a4a2cee70dd159",
            "input": "The aim of the study is to investigate whether body mass index (BMI) affected pathological characteristics and biochemical recurrence (BCR) of prostate cancer after radical prostatectomy in Chinese men.', 'Medical records of 211 Chinese patients who underwent radical prostatectomy between 2006 and 2014 were retrospectively reviewed, with follow-up time of 24.5\\u2009\u00b1\\u200927.0\\xa0months. Multivariate logistic and Cox regression analyses were applied to address the impact of BMI on adverse pathological outcomes and BCR following prostatectomy. A meta-analysis of published studies from MEDLINE or EMBASE was conducted to determine the relationship between BMI and BCR following prostatectomy among Asian populations.', 'Higher BMI was positively correlated with higher biopsy Gleason score (odds ratios (OR) 1.163, 95\\xa0% confidence interval (CI) 1.023-1.322, P\\u2009=\\u20090.021) and pathological Gleason score (OR 1.220, 95\\xa0% CI 1.056-1.410, P\\u2009=\\u20090.007) in multivariate analysis. BCR was detected in 48 patients (22.7\\xa0%). Multivariate Cox proportional hazards analysis revealed that higher BMI (hazard ratio (HR) 1.145, 95\\xa0% CI 1.029-1.273, P\\u2009=\\u20090.013) and prostate-specific antigen (HR 1.659, 95\\xa0% CI 1.102-2.497, P\\u2009=\\u20090.015) levels were independent predictors of BCR. The meta-analysis enrolled eight Asian studies of 4145 patients treated by radical prostatectomy. Based on random-effects approach, a 5\\xa0kg/m(2) increase in BMI was correlated with 28\\xa0% higher risk of BCR (HR 1.22, 95\\xa0% CI 0.86-1.72) without statistical significance.",
            "output": [
                "Is body mass index associated with higher Gleason score and biochemical recurrence risk following radical prostatectomy in Chinese men : a retrospective cohort study and meta-analysis?"
            ]
        },
        {
            "id": "task847-fef753131ecb4428bcaf4b3e298cce1f",
            "input": "\u2666', 'The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. \u2666', 'This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis (\"no-peritonitis group\") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes (\"peritonitis group\") during a follow-up of 4 years. \u2666', 'The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and \u03b12-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. \u2666",
            "output": [
                "Does the Natural Time Course of Membrane Alterations During Peritoneal Dialysis be Partly Altered by Peritonitis?"
            ]
        },
        {
            "id": "task847-08ef2ded7a2c440dbb4b454f019bb319",
            "input": "The posterior femoral offset may significantly impact the final flexion range after total knee arthroplasty (TKA). The purpose of the present study was to compare a conventional, radiologic-based technique with an intra-operative, surgical navigation-based technique for the measurement of posterior femoral offset. The tested hypothesis was that the two measurement techniques produce different results both before and after TKA.', 'One-hundred consecutive cases referred for end-stage knee osteoarthritis have been studied. Posterior femoral offsets, measured pre- and post-TKA from radiographs, as well as those measured from a navigation system intra-operatively, were analysed. The pre-TKA measured offsets, post-TKA measured offsets and the changes (pre- vs. post-TKA) in the offsets were statistically compared between the radiologic and the navigated measurement techniques at a 0.05 level of significance.', 'The mean paired difference between pre-TKA radiologic and navigated measurement was 4\\xa0\u00b1\\xa04\\xa0mm (p\\xa0<\\xa00.001). There was a significant and moderate positive correlation with a good coherence between the two measurements. The mean paired difference between post-TKA radiologic and navigated measurement was 6\\xa0\u00b1\\xa05\\xa0mm (p\\xa0<\\xa00.001). There was a significant and moderate positive correlation but a poor coherence between the two measurements.",
            "output": [
                "Is radiographic measurement of the posterior femoral offset precise?"
            ]
        },
        {
            "id": "task847-bc5d4603308247e09304dce62da425ed",
            "input": "To determine the prevalence of five physical frailty phenotype components and to assess the relationship between them and other clinical factors.', \"A population-based cross-sectional study was performed. Subjects 75 years and older were randomly selected from primary care databases (with sampling stratified by gender). Physical frailty phenotypes were assessed using Fried's criteria. Sociodemographic data, comorbidities, nutritional status, and functional capacity were assessed.\", '126 subjects were recruited (47% women). Prevalence rates were poor muscle strength: 50%; low physical activity: 29%; slow gait: 28%; exhaustion: 27%; and weight loss: 5%. Prefrailty and frailty prevalence rates were 35.7% and 29.4%, respectively. Poor muscle strength and low physical activity showed a close relationship and concordance (kappa = 0.92). Most frailty components were associated with outdoor activity, hours walked daily, and certain comorbidities.",
            "output": [
                "Do poor Muscle Strength and Low Physical Activity Are the Most Prevalent Frailty Components in Community-Dwelling Older Adults?"
            ]
        },
        {
            "id": "task847-e74b8a235f7e45188b9716064d09bfbf",
            "input": "The purpose of our study was to evaluate the relationship between graft placement and in situ graft force after anterior cruciate ligament (ACL) reconstruction.', 'Magnetic resonance imaging (MRI) was obtained for twelve human cadaveric knees. The knees, in intact and deficient-ACL states, were subjected to external loading conditions as follows: an anterior tibial load of 89 N at 0\u00b0, 15\u00b0, 30\u00b0, 45\u00b0, 60\u00b0, and 90\u00b0 of flexion and a combined rotatory (simulated pivot-shift) load of 5 Nm of internal tibial torque and 7 Nm of valgus torque at 0\u00b0, 15\u00b0, and 30\u00b0 of flexion. Three ACL reconstructions were performed in a randomized order: from the center of the tibial insertion site to the center of the femoral insertion site (Mid), the center of the tibial insertion site to a more vertical femoral position (S1), and the center of the tibial insertion site to an even more vertical femoral position (S2). The reconstructions were tested following the same protocol used for the intact state, and graft in situ force was calculated for the two loadings at each flexion angle. MRI was used to measure the graft inclination angle after each ACL reconstruction.', 'The mean inclination angle (and standard deviation) was 51.7\u00b0 \u00b1 5.0\u00b0 for the native ACL, 51.6\u00b0 \u00b1 4.1\u00b0 for the Mid reconstruction (p = 0.85), 58.7\u00b0 \u00b1 5.4\u00b0 for S1 (p < 0.001), and 64.7\u00b0 \u00b1 6.5\u00b0 for S2 (p < 0.001). At 0\u00b0, 15\u00b0, and 30\u00b0 of knee flexion, the Mid reconstruction showed in situ graft force that was closer to that of the native ACL during both anterior tibial loading and simulated pivot-shift loading than was the case for S1 and S2 reconstructions. At greater flexion angles, S1 and S2 had in situ graft force that was closer to that of the native ACL than was the case for the Mid reconstruction.",
            "output": [
                "Does aCL Graft Position affect in Situ Graft Force Following ACL Reconstruction?"
            ]
        },
        {
            "id": "task847-0bac5b69c2d747bea84222295d173b2e",
            "input": "Gastric cancer is the third leading cause of cancer-related death in China. Accumulating evidence indicates that HIF2\u03b1 may affect the aggressiveness of gastric cancer. It has also been found that HIF2\u03b1 C-terminal PAS domains can form complexes with inactive benzoxadiazole antagonists. Here, the anti-tumor effect of 4-(N,Ndimethylaminosulphonyl)-7-fluoro-1,2,3-benzoxadiazole (DBD-F) on human gastric cancer cells was examined using both in vitro and in vivo assays.', 'We found that DBD-F can induce apoptosis and inhibit the mobility of MKN28 and MKN45 gastric cancer-derived cells in vitro. We also found that DBD-F can suppress tumor growth in established gastric cancer-derived xenograft models in vivo. Finally, we found that DBD-F can inhibit HIF2\u03b1 expression in gastric cancer-derived cells.",
            "output": [
                "Does dBD-F induce apoptosis in gastric cancer-derived cells through suppressing HIF2\u03b1 expression?"
            ]
        },
        {
            "id": "task847-2b353b73eb704d7eab39718fedbb991b",
            "input": "The yeast Saccharomyces cerevisiae is unable to ferment pentose sugars like d-xylose. Through the introduction of the respective metabolic pathway, S. cerevisiae is able to ferment xylose but first utilizes d-glucose before the d-xylose can be transported and metabolized. Low affinity d-xylose uptake occurs through the endogenous hexose (Hxt) transporters. For a more robust sugar fermentation, co-consumption of d-glucose and d-xylose is desired as d-xylose fermentation is in particular prone to inhibition by compounds present in pretreated lignocellulosic feedstocks.', 'Evolutionary engineering of a d-xylose-fermenting S. cerevisiae strain lacking the major transporter HXT1-7 and GAL2 genes yielded a derivative that shows improved growth on xylose because of the expression of a normally cryptic HXT11 gene. Hxt11 also supported improved growth on d-xylose by the wild-type strain. Further selection for glucose-insensitive growth on d-xylose employing a quadruple hexokinase deletion yielded mutations at N366 of Hxt11 that reversed the transporter specificity for d-glucose into d-xylose while maintaining high d-xylose transport rates. The Hxt11 mutant enabled the efficient co-fermentation of xylose and glucose at industrially relevant sugar concentrations when expressed in a strain lacking the HXT1-7 and GAL2 genes.",
            "output": [
                "Does an engineered cryptic Hxt11 sugar transporter facilitate glucose-xylose co-consumption in Saccharomyces cerevisiae?"
            ]
        },
        {
            "id": "task847-8453c436847e4c36843c27246dd379af",
            "input": "Completeness of cytoreduction is a significant predictor of long-term outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Imaging has limited sensitivity to identify peritoneal metastases and therefore predict whether complete cytoreduction is possible. We reviewed our experience using laparoscopy to determine candidates for complete cytoreduction and HIPEC.', 'This single-center, retrospective study examined patients from 2007 to 2014 who underwent laparoscopy to determine complete cytoreduction (CC-0/1)/HIPEC candidacy. Preoperative, intraoperative, and postoperative data were collected.', 'A total of 145 laparoscopies were performed on 141 patients, 72 (51.1\\xa0%) of whom were female, with a median age of 53\\xa0years (range 20-79). The primary site was appendiceal in 67 (47.5\\xa0%) patients, colorectal in 43 (30.5\\xa0%), mesothelioma in 17 (12.1\\xa0%), unknown in 9 (6.4\\xa0%), small bowel in 3 (2.1\\xa0%), gastric in 1, and ovarian in 1 (0.7\\xa0% each). Overall, 115 (81.6\\xa0%) patients had prior abdominal surgery, 111 (76.6\\xa0%) had evidence of disease on imaging, and 117 (80.7\\xa0%) underwent prior chemotherapy, with a median of 5.9\\xa0weeks between the last treatment and laparoscopy (0.9-498.9\\xa0weeks). Four (2.8\\xa0%) intraoperative complications were observed (one liver laceration, two enterotomies, and one air embolus), and nine (6.2\\xa0%) postoperative complications [four (2.8\\xa0%) Clavien grade (CG) I, three (2.8\\xa0%) CG II, one (0.7\\xa0%) CG III (return to operating room) and one (0.7\\xa0%) CG IV (transient ischemic attack)]. Forty-eight patients deemed candidates by laparoscopy underwent CRS/HIPEC (positive predictive value 82.8\\xa0%).",
            "output": [
                "Is laparoscopy Safe and Accurate to Evaluate Peritoneal Surface Metastasis Prior to Cytoreductive Surgery?"
            ]
        },
        {
            "id": "task847-4b9082718a7a41ae9cc8253227f9584e",
            "input": "Magnifying endoscopy with narrow-band imaging (ME-NBI) is more reliable than chromoendoscopy (CE) for delineating the horizontal extent of early gastric cancers prior to endoscopic submucosal dissection (ESD). However, the added benefits of ME-NBI over CE in terms of the difference in magnification level have yet to be elucidated. The aim of this study was to investigate the improvement in diagnostic accuracy for tumor delineation obtained with different magnification levels of ME-NBI following CE.', 'This was a retrospective study, performed at a single tertiary referral center. A series of 158 consecutive patients with 161 early gastric cancers resected en bloc using ESD was included in the study. The margins of each lesion were examined in their entirety using CE, followed by low power optical magnifying endoscopy with narrow-band imaging (LM-NBI), and finally the highest power optical magnifying endoscopy with narrow-band imaging (HM-NBI). The primary endpoint was the added benefit, as measured using the successful delineation rate, for the delineation of gastric cancer margins using CE\\u2009+\\u2009LM-NBI vs CE, and for CE\\u2009+\\u2009LM-NBI\\u2009+\\u2009HM-NBI vs CE\\u2009+\\u2009LM-NBI.', 'The successful delineation rates (95 % CI) using CE, CE\\u2009+\\u2009LM-NBI and CE\\u2009+\\u2009LM-NBI\\u2009+\\u2009HM-NBI were 72.7 % (68.5-79.9 %), 88.9 % (84.2-93.8 %), and 98.1 % (95.8-100 %). The diagnostic accuracy improved significantly for CE\\u2009+\\u2009LM-NBI compared with CE (P\\u2009<\\u20090.001), and for HM-NBI compared with LM-NBI (P\\u2009<\\u20090.001).",
            "output": [
                "Is highest power magnification with narrow-band imaging useful for improving diagnostic performance for endoscopic delineation of early gastric cancers?"
            ]
        },
        {
            "id": "task847-79eddd2551e644e9a4582040c73d0f96",
            "input": "Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling.', 'Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups.",
            "output": [
                "Does semaphorin 3a transfection into the left stellate ganglion reduce susceptibility to ventricular arrhythmias after myocardial infarction in rats?"
            ]
        },
        {
            "id": "task847-1818efff83c24f6980527d25bb29172a",
            "input": "Breast sarcomas are rare, usually occurring in the setting of malignant phyllodes tumour (MPT). Heterologous differentiation commonly resembles well-differentiated or pleomorphic liposarcoma. In extramammary sites, these subtypes have different biological behaviours and distinct genetic alterations: MDM2 and CDK4 amplification in well-differentiated liposarcoma, and polyploidy with complex structural rearrangements in pleomorphic liposarcoma. The aim of this study was to investigate foci resembling well-differentiated liposarcoma in MPT for MDM2 and CDK4 amplification.', 'We evaluated the clinicopathological characteristics of MPTs received by the Vanderbilt Breast Consultation Service containing components resembling well-differentiated or pleomorphic liposarcoma. Cases with available tissue blocks were subjected to fluorescence in-situ hybridization with MDM2 and CDK4 probes. Thirty-eight MPTs with liposarcomatous components were available for review. The mean patient age was 49.8 years (range 26-84 years). In addition to well-differentiated liposarcoma, the following components were also present: high-grade undifferentiated sarcoma (n = 9; 23.7%), pleomorphic liposarcoma (n = 4; 10.5%), non-high-grade sarcoma not otherwise specified (n = 22; 57.9%), and malignant peripheral nerve sheath tumour-like (n = 2; 5.2%). Among 10 cases tested, none showed amplification of MDM2 or CDK4.",
            "output": [
                "Is liposarcomatous differentiation in malignant phyllodes tumours unassociated with MDM2 or CDK4 amplification?"
            ]
        },
        {
            "id": "task847-15789b043c9c4c18833b9dcd73138c34",
            "input": "Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear.', 'To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts.', 'Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures.', 'Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot.', 'Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways.",
            "output": [
                "Does citrus limonoid nomilin inhibit osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways?"
            ]
        },
        {
            "id": "task847-7e73812386c54912bf362c6c327d1730",
            "input": "To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC).', 'Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone.', 'Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone.",
            "output": [
                "Does strong Notch activation hinder bevacizumab efficacy in advanced colorectal cancer?"
            ]
        },
        {
            "id": "task847-16596927f7f24a9aa5998dc12209b0cd",
            "input": "To investigate intermittent hypoxia (IH) induced changes in craniofacial morphology and bone mineral density (BMD) in the mandible of growing rats.', 'Seven-week-old male Sprague-Dawley rats were exposed to IH for 4 days or 3 weeks. Sham-operated rats simultaneously breathed room air. Lateral and transverse cephalometric radiographs of the craniofacial region were obtained, and the linear distances between cephalometric landmarks were statistically analyzed. BMD and bone microstructure of the mandible were evaluated using micro-computed tomography (micro-CT).', 'Cephalometric analyses demonstrated that exposure to IH only in the two groups for 3 weeks decreased the size of the mandibular and viscerocranial bones, but not that of the neurocranial bones, in early adolescent rats. These findings are consistent with upper airway narrowing and obstructive sleep apnea (OSA). Micro-CT showed that IH increased the BMD in the cancellous bone of the mandibular condyle and the inter-radicular alveolar bone in the mandibular first molar (M1) region.",
            "output": [
                "Does intermittent hypoxia induce disturbances in craniofacial growth and defects in craniofacial morphology?"
            ]
        },
        {
            "id": "task847-f8837d6364c14f48bedb89a93f5522f0",
            "input": "Point-of-care ultrasound evaluates inferior vena cava (IVC) and internal jugular vein (IJV) measurements to estimate intravascular volume status. The reliability of the IVC and IJV collapsibility index during increased thoracic or intra-abdominal pressure remains unclear.', \"Three phases of sonographic scanning were performed: spontaneous breathing phase, increased thoracic pressure phase via positive pressure ventilation (PPV) phase, and increased intra-abdominal pressure (IAP) phase via laparoscopic insufflation to 15\\xa0mmHg. IVC measurements were done at 1-2\\xa0cm below the diaphragm and IJV measurements were done at the level of the cricoid cartilage during a complete respiratory cycle. Collapsibility index was calculated by (max diameter\\xa0-\\xa0min diameter)/max diameter\\xa0\u00d7\\xa0100\\xa0%. Chi square, t test, correlation procedure (CORR) and Fisher's exact analyses were completed.\", 'A total of 144 scans of the IVC and IJV were completed in 16 patients who underwent laparoscopic surgery. Mean age was 46\\xa0\u00b1\\xa015\\xa0years, with 75\\xa0% female and 69\\xa0% African-American. IVC and IJV collapsibility correlated in the setting of spontaneous breathing (r (2)\\xa0=\\xa00.86, p\\xa0<\\xa00.01). IVC collapsibility had no correlation with the IJV in the setting of PPV (r (2)\\xa0=\\xa00.21, p\\xa0=\\xa00.52) or IAP (r (2)\\xa0=\\xa00.26, p\\xa0=\\xa00.42). Maximal IVC diameter was significantly smaller during increased IAP (16.5\\xa0mm\\xa0\u00b1\\xa04.9) compared to spontaneous breathing (20.6\\xa0mm\\xa0\u00b1\\xa04.8, p\\xa0=\\xa00.04) and PPV (21.8\\xa0mm\\xa0\u00b1\\xa05.6, p\\xa0=\\xa00.01).",
            "output": [
                "Does inferior vena cava collapsibility lose correlation with internal jugular vein collapsibility during increased thoracic or intra-abdominal pressure?"
            ]
        },
        {
            "id": "task847-771a0c8c2f3e421392b449ae997063ab",
            "input": "We investigated parent-of-origin and allele-specific expression effects on obesity and hepatic gene expression in reciprocal crosses between the Berlin Fat Mouse Inbred line (BFMI) and C57Bl/6NCrl (B6N).', 'We found that F1-males with a BFMI mother developed 1.8 times more fat mass on a high fat diet at 10 weeks than F1-males of a BFMI father. The phenotype was detectable from six weeks on and was preserved after cross-fostering. RNA-seq data of liver provided evidence for higher biosynthesis and elongation of fatty acids (p\\u2009=\\u20090.00635) in obese male offspring of a BFMI mother versus lean offspring of a BFMI father. Furthermore, fatty acid degradation (p\\u2009=\\u20090.00198) and the peroxisome pathway were impaired (p\\u2009=\\u20090.00094). The circadian rhythm was affected as well (p\\u2009=\\u20090.00087). Among the highest up-regulated protein coding genes in obese males were Acot4 (1.82 fold, p\\u2009=\\u20090.022), Cyp4a10 (1.35 fold, p\\u2009=\\u20090.026) and Cyp4a14 (1.32 fold, p\\u2009=\\u20090.012), which hydroxylize fatty acids and which are known to be increased in liver steatosis. Obese males showed lower expression of the genetically imprinted and paternally expressed 3 (Peg3) gene (0.31 fold, p\\u2009=\\u20090.046) and higher expression of the androgen receptor (Ar) gene (2.38 fold, p\\u2009=\\u20090.068). Allelic imbalance was found for expression of ATP-binding cassette transporter gene Abca8b. Several of the differentially expressed genes contain estrogen response elements.",
            "output": [
                "Does the direction of cross affect [ corrected ] obesity after puberty in male but not female offspring?"
            ]
        },
        {
            "id": "task847-764dc59ac7324e9dafa2b7c9d64a47dc",
            "input": "The purpose of this study was to compare prenatal versus postnatal markers of congenital diaphragmatic hernia (CDH) severity at a single fetal-care center.', 'A retrospective study was performed of patients having a complete prenatal evaluation and surgical repair (n\\u2009=\\u200955). Observed-to-expected lung-to-head ratio (o/eLHR), observed-to-expected total lung volume (o/eTLV), liver position (LP), a predictive dependent variable from logistic regression of o/eLHR and liver position (o/eLHR\\u2009+\\u2009LP), and diaphragmatic defect size per the CDH Study Group A-D classification were plotted into receiver-operating characteristics (ROC) curves. Survival and need for extracorporeal membrane oxygenation (ECMO) were primary outcomes.', 'Survival was 69%, and ECMO utilization was 56%. Distribution was 80% left-sided defects. In the survival ROC curve, the area under the curve (AUC) for o/eLHR was 0.73, o/eTLV 0.74, LP 0.73, o/eLHR\\u2009+\\u2009LP 0.78, and defect size 0.84 (p\\u2009=\\u20090.23). The ROC curve for ECMO support showed o/eLHR had an AUC of 0.82, o/eTLV 0.89, LP 0.79, o/eLHR\\u2009+\\u2009LP 0.87, and defect size 0.90 (p\\u2009=\\u20090.19). The AUCs were similar when only left-sided CDH was analyzed.",
            "output": [
                "Do prenatal and postnatal markers of severity in congenital diaphragmatic hernia have similar prognostic ability?"
            ]
        },
        {
            "id": "task847-8405b59245664d9da2347b4c99747c31",
            "input": "The role of autophagy in moderate hypothermia in posttraumatic brain injury (post-TBI) remains elusive. In this study, we evaluated the protective role of autophagy in post-TBI moderate hypothermia.', 'Adult male Sprague-Dawley rats were randomly divided into 3 groups (n\\xa0= 36/group): TBI with hypothermia group (sham), TBI with hypothermia and a single intracerebroventricular injection of saline (saline, 5 \u03bcL), and TBI with hypothermia and a single intracerebroventricular injection of 3-methyladenine (600 nmol, diluted in 0.9% saline to a final volume of 5 \u03bcL). All rats, except those in the behavioral tests, were killed at 24 hours after fluid percussion TBI. Immunohistochemistry staining, western blot, and transmission electron microscopy were performed to assess changes in apoptosis and autophagy after injection of 3-methyladenine. Motor function (beam-walk test) and spatial learning/memory (Morris water maze) were assessed on postoperative days 1-5 and 11-15, respectively.', 'Our results showed downregulation of the expression level of microtubule-associated protein 1 light chain 3 and Beclin-1, aggravation of behavioral outcome, and increase of apoptosis.",
            "output": [
                "Does autophagy Inhibitor 3-MA weaken Neuroprotective Effects of Posttraumatic Brain Injury Moderate Hypothermia?"
            ]
        },
        {
            "id": "task847-9cf9f7338b1248959154a337abd040ea",
            "input": "Endothelium-derived nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in modulating vascular tone in a distinct vessel size-dependent manner; NO plays a dominant role in conduit arteries and EDH in resistance vessels. We have recently demonstrated that endothelial NO synthase (eNOS) is functionally suppressed in resistance vessels through caveolin-1 (Cav-1)-dependent mechanism, switching its function from NO to EDH/hydrogen peroxide generation in mice. Here, we examined the possible importance of the physiological balance between NO and EDH in cardiovascular homeostasis.', 'We used 2 genotypes of mice in which eNOS activity is genetically upregulated; Cav-1-knockout (Cav-1-KO) and endothelium-specific eNOS transgenic (eNOS-Tg) mice. Isometric tension recordings and Langendorff experiments with isolated perfused hearts showed that NO-mediated relaxations were significantly enhanced, whereas EDH-mediated relaxations were markedly reduced in microcirculations. Importantly, impaired EDH-mediated relaxations of small mesenteric arteries from Cav-1-KO mice were completely rescued by crossing the mice with those with endothelium-specific overexpression of Cav-1. Furthermore, both genotypes showed altered cardiovascular phenotypes, including cardiac hypertrophy in Cav-1-KO mice and hypotension in eNOS-Tg mice. Finally, we examined cardiac responses to chronic pressure overload by transverse aortic constriction in vivo. When compared with wild-type mice, both Cav-1-KO and eNOS-Tg mice exhibited reduced survival after transverse aortic constriction associated with accelerated left ventricular systolic dysfunction, reduced coronary flow reserve, and enhanced myocardial hypoxia.",
            "output": [
                "Does disruption of Physiological Balance Between Nitric Oxide and Endothelium-Dependent Hyperpolarization impair Cardiovascular Homeostasis in Mice?"
            ]
        },
        {
            "id": "task847-d5cae57717ac4e26ae1726bff4b993c1",
            "input": "Sensitisation with Aspergillus fumigatus (Af) is known to be associated with severe allergic lung inflammation, but the mechanism remains to be clarified. Phosphoinositide 3-kinase (PI3K)-\u03b4 and endoplasmic reticulum (ER) stress are suggested to be involved in steroid-resistant lung inflammation. We aimed to elucidate the role of PI3K-\u03b4 and its relationship with ER stress in fungus-induced allergic lung inflammation.', 'Using Af-exposed in vivo and in vitro experimental systems, we examined whether PI3K-\u03b4 regulates ER stress, thereby contributing to steroid resistance in fungus-induced allergic lung inflammation. Moreover, we checked expression of an ER stress marker in lung tissues isolated from patients with allergic bronchopulmonary aspergillosis.', 'Af-exposed mice showed that ER stress markers, unfolded protein response (UPR)-related proteins, phosphorylated Akt, generation of mitochondrial reactive oxygen species (mtROS), eosinophilic allergic inflammation, and airway hyperresponsiveness (AHR) were increased in the lung. Similarly, glucose-regulated protein 78 was increased in lung tissues of patients with ABPA. A PI3K-\u03b4 inhibitor reduced Af-induced increases in ER stress markers, UPR-related proteins, allergic inflammation and AHR in mice. However, dexamethasone failed to reduce Af-induced allergic inflammation, AHR and elevation of ER stress. Administration of an ER stress inhibitor or a mtROS scavenger improved Af-induced allergic inflammation. The PI3K-\u03b4 inhibitor reduced Af-induced mtROS generation and the mtROS scavenger ameliorated ER stress. In primary cultured tracheal epithelial cells, Af-induced ER stress was inhibited by blockade of PI3K-\u03b4.",
            "output": [
                "Does phosphoinositide 3-kinase-\u03b4 regulate fungus-induced allergic lung inflammation through endoplasmic reticulum stress?"
            ]
        },
        {
            "id": "task847-24654bdd45ff4d9ca0e9c087fc5efcfd",
            "input": "Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease marked by both B and T cell hyperactivity which commonly affects the joints, skin, kidneys, and brain. Neuropsychiatric disease affects about 40\\xa0% of SLE patients, most frequently manifesting as depression, memory deficits, and general cognitive decline. One important and yet unresolved question is whether neuropsychiatric SLE (NPSLE) is a complication of systemic autoimmunity or whether it is primarily driven by brain-intrinsic factors.', 'To dissect the relative contributions of the central nervous system from those of the hematopoietic compartment, we generated bone marrow chimeras between healthy control (MRL/+) and lupus-prone MRL/Tnfrsf6 (lpr/lpr) mice (MRL/+\\u2009\u2192\\u2009MRL/lpr), as well as control chimeras. After bone marrow reconstitution, mice underwent extensive behavioral testing, analysis of brain tissue, and histological assessment.', 'Despite transfer of healthy MRL/+ bone marrow and marked attenuation of systemic disease, we found that MRL/+\\u2009\u2192\\u2009MRL/lpr mice had a behavioral phenotype consisting of depressive-like behavior and visuospatial memory deficits, comparable to MRL/lpr\\u2009\u2192\\u2009MRL/lpr control transplanted mice and the behavioral profile previously established in MRL/lpr mice. Moreover, MRL/+\\u2009\u2192\\u2009MRL/lpr chimeric mice displayed increased brain RANTES expression, neurodegeneration, and cellular infiltration in the choroid plexus, as well as blood brain barrier disruption, all in the absence of significant systemic autoimmunity.",
            "output": [
                "Does neuropsychiatric systemic lupus erythematosus persist despite attenuation of systemic disease in MRL/lpr mice?"
            ]
        },
        {
            "id": "task847-9fc00b86ec634f2f86f23e4421fc024a",
            "input": "Previous studies have shown that Astragalus polysaccharide (APS) can be applied to anti-cancer. However, the mechanism by which APS mediate this effect is unclear. In the present study, APS-mediated NSCLC cell apoptosis was investigated through the regulation of the notch signaling pathway.', 'The cell viability was detected by the CCK8 assay. The mRNA and protein expression of notch1/3 and tumor suppressors were analyzed by RT-PCR and western blotting, respectively.', 'The mRNA and protein of notch1 and notch3 were significantly up-regulated in tumor tissues as compared to non-tumor adjacent tissues. Treatment of human NSCLC cells with APS induced cell death in a dose-and time-dependent manner by using CCK8 assay. The mRNA and protein expression of notch1 and notch3 were significantly lower in NSCLC cells with APS treatment than that in control group. Moreover, western blotting analysis showed that treatment of H460 cells with APS significantly increased the pro-apoptotic Bax and caspase 8 levels, decreased the anti-apoptotic Bcl-2 level. Furthermore, p53, p21 and p16 were obviously up-regulated by APS treatment in H460 cell.",
            "output": [
                "Are notch1/3 and p53/p21 a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines?"
            ]
        },
        {
            "id": "task847-9f043fe32a104464a0617fd9d893328a",
            "input": "To compare the relative value of magnetic resonance imaging (MRI) in biopsy-naive patients to those with previous negative biopsy. Although MRI-targeted biopsy has been studied in several major prostate cancer (PCa) cohorts (biopsy naive, previous negative biopsy, and active surveillance), the relative benefit in these cohorts has not been established.', 'We retrospectively reviewed biopsy-naive (n = 45) and previous negative biopsy (n = 55) patients who underwent prostate MRI prior to biopsy at our institution. Patients with an MRI suspicious region (MSR) underwent MRI-targeted biopsy as well as a systematic template biopsy, whereas those without MSR underwent only the template biopsy. All biopsies were performed with the TargetScan (Envisioneering, Pittsburgh, PA) biopsy system. MRI targeting was performed with cognitive guidance.', 'On multivariate logistic regression, the presence of an MSR was the only statistically significant and independent predictor of Gleason \u2265 7 PCa on biopsy for biopsy-naive men (odds ratio [OR] 40.2, P = .01). For men with previous negative biopsy, the presence of MSR was not a predictor of Gleason \u2265 7 PCa on biopsy (OR 4.35, P = .16), whereas PSA density > 0.15 ng/mL(2) was a significant and independent predictor (OR 66.2, P < .01).",
            "output": [
                "Does presence of Magnetic Resonance Imaging Suspicious Lesion predict Gleason 7 or Greater Prostate Cancer in Biopsy-Naive Patients?"
            ]
        },
        {
            "id": "task847-00189312b41c4d6d986772485007876b",
            "input": "To facilitate indefinite proliferation, stem cells and most cancer cells require the activity of telomerase, which counteracts the successive shortening of telomeres caused by incomplete DNA replication at the very end of each chromosome. Human telomerase activity is often determined by the expression level of telomerase reverse transcriptase (TERT), the catalytic subunit of the ribonucleoprotein complex. The low expression level of TERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes in human cells.', 'To overcome the low CRISPR-Cas9 editing efficiency at the TERT locus, we develop a two-step \"pop-in/pop-out\" strategy to enrich cells that underwent homologous recombination (HR). Using this technique, we fuse an N-terminal FLAG-SNAP-tag to TERT, which allows us to reliably detect TERT in western blots, immunopurify it for biochemical analysis, and determine its subcellular localization by fluorescence microscopy. TERT co-localizes detectably with only 5-7 % of the telomeres at a time in S-phase HeLa cells; no nucleolar localization is detected. Furthermore, we extend this approach to perform single base-pair modifications in the TERT promoter; reverting a recurrent cancer-associated TERT promoter mutation in a urothelial cancer cell line results in decreased telomerase activity, indicating the mutation is causal for telomerase reactivation.",
            "output": [
                "Does a novel two-step genome editing strategy with CRISPR-Cas9 provide new insights into telomerase action and TERT gene expression?"
            ]
        },
        {
            "id": "task847-d93a02839ed64f9ab9b489eb76c2ba56",
            "input": "Several association studies confirmed high-mobility group-A2 gene (HMGA2) polymorphisms as the most relevant variants contributing to height variability. Animal models and deletions in humans suggest that alterations of HMGA2 might be relevant in causing short stature. Together, these observations led us to investigate the involvement of HMGA2 in idiopathic short stature (ISS) through an association study and a mutation screening.', 'We conducted an association study (155 ISS patients and 318 normal stature controls) with three HMGA2 single-nucleotide polymorphisms (SNPs) (SNPs rs1042725, rs7968682, and rs7968902) using a TaqMan-based assay. The patients were then analyzed by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) to detect point mutations and genomic micro-rearrangements.', 'Considering a recessive model, an OR value >1 was observed for genotypes rs7968682 TT (Odds ratio (OR) = 1.72, confidence interval (CI): 1.14-2.58) and rs1042725 TT (OR = 1.51, CI: 1.00-2.28) in accordance to the effect exhibited by the single alleles in the general population. None of the patients carried possibly causative HMGA2 mutations.",
            "output": [
                "Are variations in the high-mobility group-A2 gene ( HMGA2 ) associated with idiopathic short stature?"
            ]
        },
        {
            "id": "task847-21fc151bb44a45188748f01d39c7920e",
            "input": "A cross-sectional study.', 'This study aims to investigate the correlation of the cervical canal and spinal cord size, and evaluate whether the size of the spinal cord relative to the spinal canal is a risk factor for development of cervical spinal cord compression (SCC).', 'There is little knowledge regarding the relationship between cervical bony canal and spinal cord diameters. Although developmental canal stenosis has been recognized as a risk factor for SCC, the size of the spinal cord relative to the spinal canal has not been similarly discussed.', 'Cervical canal anteroposterior (AP) diameters on X-rays and AP diameters and cross-sectional areas of dural sacs and spinal cords on magnetic resonance imaging (MRI) were measured in 1211 healthy volunteers. Correlation between cervical canal diameter on X-rays and AP diameter and cross-sectional area of dural sacs and spinal cords on MRI were assessed. The ratio of the AP diameter of the spinal cord/dural sac was compared between subjects with and without SCC.', 'Spinal canal diameters were not highly correlated with spinal cord AP diameters and cross-sectional areas, although spinal canal diameters were significantly correlated with dural sac AP diameters. The individual difference in the ratio of the AP diameter of the spinal cord/dural sac was large (35%-93%), and the ratio was significantly larger in the subjects with SCC. An AP diameter ratio more than 62% at the C2 to C3 disc level is a risk factor for developing SCC.",
            "output": [
                "Is relatively Large Cervical Spinal Cord for Spinal Canal a Risk factor for Development of Cervical Spinal Cord Compression : A Cross-Sectional Study of 1211 Subjects?"
            ]
        },
        {
            "id": "task847-1a0ec8cc21564ca5a991146a56f903f8",
            "input": "To become a parent is an emotionally life-changing experience. Paternal depression during the postnatal period has been associated with emotional and behavioral problems in children. The condition has predominantly been related to mothers, and the recognition of paternal postnatal depression (PND) has been paid less attention to. PND in fathers may be difficult to detect. However, nurses in pediatric services meet a lot of fathers and are in a position to detect a father who is suffering from PND. Therefore, the aim of this study was (a) to explore Child Health Center nurses' experiences of observing depression in fathers during the postnatal period; and (b) to explore hindrances of observing these fathers.\", 'A qualitative descriptive study was conducted. Ten nurses were interviewed in 2014. A thematic data analysis was performed and data were analyzed for meaning.', 'Paternal PND was experienced as being vague and difficult to detect. Experiences of fathers with such problems were limited, and it was hard to grasp the health status of the fathers, something which was further complicated when routines were lacking or when gender attitudes influenced the daily work of the nurses.",
            "output": [
                "Are we also interested in how fathers feel : a qualitative exploration of child health center nurses ' recognition of postnatal depression in fathers?"
            ]
        },
        {
            "id": "task847-81e4a570734b491aa854081b6c6958e4",
            "input": "Proper fluoroscopic education and protocols may reduce the patient radiation dose but few prospective studies in urology have been performed. Using optically stimulated luminescent dosimeters we tested whether fluoroscopy time and/or entrance skin dose would decrease after educational and radiation reduction protocols.', 'At default manufacturer settings fluoroscopy time and entrance skin dose were prospectively measured using optically stimulated luminescent dosimeters in patients undergoing ureteroscopy, retrograde pyelogram/stent or percutaneous nephrolithotomy with access for stone disease. A\\xa0validated radiation safety competency test was administered to urology faculty and residents before and after web based, hands-on fluoroscopy training. Default\\xa0fluoroscopy settings were changed from continuous to intermittent pulse\\xa0rate and from standard to half-dose output. Fluoroscopy time and entrance skin dose were then measured again.', 'The cohorts of 44 pre-protocol and 50 post-protocol patients with stones were similarly matched. The change in mean fluoroscopy time and entrance skin dose from pre-protocol to post-protocol was -0.6 minutes and -11.6 mGy (33%) for percutaneous nephrolithotomy (p = 0.62 and <0.001), 0.5 minutes and -0.1\\xa0mGy (34%) for ureteroscopy (p = 0.42 and 0.31), and 0.1 minute and -0.1 mGy (29%) for retrograde pyelogram/stent (p = 0.85 and 0.49, respectively). Urologist post-training test scores increased 30% from pretraining scores (p\\xa0=\\xa00.1).",
            "output": [
                "Does changing Default Fluoroscopy Equipment Settings decrease Entrance Skin Dose in Patients?"
            ]
        },
        {
            "id": "task847-b48cc49e730a43c2b18c72ceed5820ab",
            "input": "This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus.', 'Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats.', 'Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration.",
            "output": [
                "Does monosialotetrahexosylganglioside inhibit the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus?"
            ]
        },
        {
            "id": "task847-cfc7ea07126c433cbc25ea33fa137cf1",
            "input": "The orphan G protein-coupled receptor (GPR) 39 was originally identified as the receptor of obestatin. In this study, the effects and mechanisms of GPR39 on cell proliferation and differentiation were investigated in cultured porcine intramuscular preadipocytes.', 'Morphology of preadipocytes and accumulated lipid droplets within cells were identified by an inverted microscope. After transfected with constructed pCMV-GPR39 plasmid, cell proliferation was measured by using methyl thiazolyl tetrazolium method, mRNA expression of GPR39, CCAAT/enhancer binding protein-\u03b1 (C/EBP\u03b1), peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3), Caspase-9 and adipocyte determination and differentiation factor-1 (ADD1) was determined by RNA preparation and reverse transcription polymerase chain reaction, protein expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1, phosphorylated glycogen synthase kinase 3 (pGSK3), total Akt and phosphorylated Akt (pAkt) was analyzed by Western blot.', 'It found that GPR39 mRNA and protein were expressed in porcine intramuscular preadipocytes and its expression was significantly up-regulated after treatment with Zn(2+) whose function is found to be mediated by GPR39. Furthermore, over-expression of GPR39 further promoted the optical density value of cells, enhanced mRNA expression of PPAR\u03b3, C/EBP\u03b1 and ADD1, and inhibited mRNA expression of Caspase-9. Protein expression of pGSK3 and pAkt was also increased by GPR39 stimulation. In addition, GPR39-induced proliferation and differentiation of porcine intramuscular preadipocytes was partially blocked by the Akt inhibitor (PDTC) and the PI3K inhibitor (LY294002).",
            "output": [
                "Does gPR39 activate proliferation and differentiation of porcine intramuscular preadipocytes through targeting the PI3K/AKT cell signaling pathway?"
            ]
        },
        {
            "id": "task847-cc6ae61b690c4721862ef2fbe502faab",
            "input": "To investigate the independent relationship of individual- and area-level socio-economic status (SES) with the presence and severity of visual impairment (VI) in an Asian population.', 'Cross-sectional data from 9993 Chinese, Malay and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of eye Diseases (2004-2011) in Singapore. Based on the presenting visual acuity (PVA) in the better-seeing eye, VI was categorized into normal vision (logMAR\u22640.30), low vision (logMAR>0.30<1.00), and blindness (logMAR\u22651.00). Any VI was defined as low vision/blindness in the PVA of better-seeing eye. Individual-level low-SES was defined as a composite of primary-level education, monthly income<2000 SGD and residing in 1 or 2-room public apartment. An area-level SES was assessed using a socio-economic disadvantage index (SEDI), created using 12 variables from the 2010 Singapore census. A high SEDI score indicates a relatively poor SES. Associations between SES measures and presence and severity of VI were examined using multi-level, mixed-effects logistic and multinomial regression models.', 'The age-adjusted prevalence of any VI was 19.62% (low vision = 19%, blindness = 0.62%). Both individual- and area-level SES were positively associated with any VI and low vision after adjusting for confounders. The odds ratio (95% confidence interval) of any VI was 2.11(1.88-2.37) for low-SES and 1.07(1.02-1.13) per 1 standard deviation increase in SEDI. When stratified by unilateral/bilateral categories, while low SES showed significant associations with all categories, SEDI showed a significant association with bilateral low vision only. The association between low SES and any VI remained significant among all age, gender and ethnic sub-groups. Although a consistent positive association was observed between area-level SEDI and any VI, the associations were significant among participants aged 40-65 years and male.",
            "output": [
                "Do composite Measures of Individual and Area-Level Socio-Economic Status Are Associated with Visual Impairment in Singapore?"
            ]
        },
        {
            "id": "task847-5af043ea7d024a4ca3df0df0db8fb72f",
            "input": "To determine if neuromuscular electrical stimulation (NMES) applied to the ankle dorsiflexors during gait improves muscle volume and strength in children with unilateral spastic cerebral palsy (CP).', 'Thirty-two children (15 females, 17 males; mean age 10y 8mo, age range 5y 5mo-18y 1mo) with unilateral spastic CP and a Gross Motor Function Classification System of level I or level II were randomly assigned to either the 8-week daily NMES treatment group or control group (usual or conventional treatments). Outcomes at week 8 (post-NMES) and week 14 (carryover) included magnetic resonance imaging for muscle volumes (tibialis anterior, anterior compartment, and gastrocnemius), strength (hand-held dynamometry for isometric dorsiflexion strength and heel raises for functional strength), and clinical measures for lower limb selective motor control.', 'At week 8, the treatment group demonstrated significantly (p<0.05) increased muscle volumes for tibialis anterior, anterior compartment, medial and lateral gastrocnemius, and dorsiflexion strength not only when compared to their baseline values but also when compared to the control group at week 8. At week 14, both tibialis anterior and lateral gastrocnemius volumes in the treatment group remained significantly increased when compared to their baseline values. However, only lateral gastrocnemius volumes had significantly greater values when compared to the control group at week 14. There were no between group differences in the clinical measures for lower limb selective motor control at week 8 and 14.",
            "output": [
                "Does neuromuscular electrical stimulation-assisted gait increase muscle strength and volume in children with unilateral spastic cerebral palsy?"
            ]
        },
        {
            "id": "task847-bee70d0ba2b2472d9e987e8cbc10fc6e",
            "input": "To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change.', 'Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach.', 'Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes.",
            "output": [
                "Do a Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke?"
            ]
        },
        {
            "id": "task847-b105b1c92f4047e096b2057bb91d3de6",
            "input": "Post-traumatic pulmonary embolic events are associated with significant morbidity. Computed tomographic (CT) measurements can be predictive of right ventricular (RV) dysfunction after pulmonary embolus. However, it remains unclear whether these physiologic effects or clinical outcomes differ between early (<48 hours) vs late (\u226548 hours) post-traumatic pulmonary embolism (PE).', 'All patients with traumatic injury and CT evidence of PE between 2008 and 2013 were identified. The study population was divided into 2 groups based on the time of diagnosis of the PE. The primary outcome was PE-related mortality.', 'Fifty patients were identified (14 early PE and 36 late PE). Patients sustaining a late PE had a higher PE-related mortality rate (16.7% vs 0%), larger RV diameters, RV/left ventricular diameter ratios, RV volumes, and RV/left ventricular volume ratios (all P < .05).",
            "output": [
                "Is immediate post-traumatic pulmonary embolism associated with right ventricular dysfunction?"
            ]
        },
        {
            "id": "task847-29d2b898fea3471f8df3f133c4584f2e",
            "input": "The extent of ischemic injury in response to cerebral ischemia is known to be affected by native vasculature. However, the nonvascular and dynamic vascular responses and their genetic basis are not well understood.', 'We performed a genome-wide association study in 235 mice from 33 inbred strains using the middle cerebral artery occlusion model. Population structure and genetic relatedness were accounted for using the efficient mixed-model association method. Human orthologs to the genes associated with the significant and suggestive single-nucleotide polymorphisms from the mouse strain survey were examined in patients with M1 occlusions admitted with signs and symptoms of acute ischemic stroke.', 'We identified 4 genome-wide significant and suggestive single-nucleotide polymorphisms to be associated with infarct volume in mice (rs3694965, P=2.17\u00d710(-7); rs31924033, P=5.61\u00d710(-6); rs32249495, P=2.08\u00d710(-7); and rs3677406, P=9.56\u00d710(-6)). rs32249495, which corresponds to angiopoietin-1 (ANGPT1), was also significant in the recessive model in humans, whereas rs1944577, which corresponds to ZBTB7C, was nominally significant in both the additive and dominant genetic models in humans. ZBTB7C was shown to be upregulated in endothelial cells using both in vitro and in vivo models of ischemia.",
            "output": [
                "Do integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury?"
            ]
        },
        {
            "id": "task847-fb0eec1242ed4c078e93d8c75d40a23a",
            "input": "Direct comparison of enzymatic and original blue cell-counting detections with the multinuclear activation of an indicator (MAGI) cells, so far, remains to be performed in parallel. Although inhibitors for reverse transcription solely inhibit the reverse transcription step, those for HIV-1 entry block syncytium formation of HIV-1-infected MAGI cells in addition to the entry (dual inhibition). It raises a concern that reduction of enzymatic activity is artificially influenced by syncytium-blocking activity of inhibitors for entry.', 'The MAGI cells with a syncytium inducible strain, HIV-1IIIB, were used for anti-HIV activity determination both with conventional counting with X-Gal staining and measurement of chlorophenol red \u03b2-d-galactopyranoside conversion with a plate reader.', 'Infectivity of HIV-1 in the MAGI cells was highly correlated with both methods. In microscopic observation, small blue cells with single or a couple of nuclei were dominantly observed in the presence of inhibitors for entry, but not in the presence of those for reverse transcription. Actual anti-HIV-1 activities were comparable or moderately sensitive in the chlorophenol red \u03b2-d-galactopyranoside method.",
            "output": [
                "Is anti-HIV-1 activity determined by \u03b2-galactosidase activity in the multinuclear activation of an indicator assay comparable with that by a conventional focus counting method?"
            ]
        },
        {
            "id": "task847-cc28dbf5b21e4aaa88dbafab39a98d63",
            "input": "MicroRNAs play important roles in regulation of the initiation and progression of AML. MiR-210 is closely related with cancer development; however, whether miR-210 expression level correlates with clinical correlation in AML is unknown. Thus, the aim of this study was to investigate the potential relationship between miR-210 expression and AML prognosis.', 'Real-time quantitative PCR was carried out to examine the expression level of miR-210 in bone marrow and serum obtained from AML patients and healthy controls. Then the correlation between miR-210 expression and a variety of important clinical parameters (such as overall survival, relapse-free survival, and prognostic value) were further studied.', 'The expression level of miR-210 was significantly higher in the bone marrow and serum of AML patients than that of healthy controls (p<0.001). Moreover, miR-210 expression was associated with various AML clinicopathological parameters, including FAB classification and cytogenetics. The serum miR-210 expression level was reduced significantly when the patients achieved complete remission (p=0.02). The high miR-210 expression group had both poorer relapse-free survival (p=0.015) and worse overall survival (p=0.008). In the multivariate analysis model, miR-210 was identified as an independent prognostic marker.",
            "output": [
                "Is overexpression of miR-210 Associated with Poor Prognosis of Acute Myeloid Leukemia?"
            ]
        },
        {
            "id": "task847-46dc519ac6a94c2f8a082c32a32d1bea",
            "input": "To determine whether the number of words displayed in the word prediction software (WPS) list affects text input speed (TIS) in people with cervical spinal cord injury (SCI), and whether any influence is dependent on the level of the lesion.', 'A cross-sectional trial.', 'A rehabilitation center.', 'Persons with cervical SCI (N=45). Lesion level was high (C4 and C5, American Spinal Injury Association [ASIA] grade A or B) for 15 participants (high-lesion group) and low (between C6 and C8, ASIA grade A or B) for 30 participants (low-lesion group).', 'TIS was evaluated during four 10-minute copying tasks: (1) without WPS (Without); (2) with a display of 3 predicted words (3Words); (3) with a display of 6 predicted words (6Words); and (4) with a display of 8 predicted words (8Words).', 'During the 4 copying tasks, TIS was measured objectively (characters per minute, number of errors) and subjectively through subject report (fatigue, perception of speed, cognitive load, satisfaction).', 'For participants with low-cervical SCI, TIS without WPS was faster than with WPS, regardless of the number of words displayed (P<.001). For participants with high-cervical SCI, the use of WPS did not influence TIS (P=.99). There was no influence of the number of words displayed in a word prediction list on TIS; however, perception of TIS differed according to lesion level.",
            "output": [
                "Do influence of the Number of Predicted Words on Text Input Speed in Participants With Cervical Spinal Cord Injury?"
            ]
        },
        {
            "id": "task847-484b389c59e44692afeec2e407645350",
            "input": "FEV6 can be used as a convenient alternative to FVC. The aim of this study was to determine an alternative to the fixed cutoff points of FEV1/FVC <0.70 suitable for FEV1/FEV6 in primary care.', \"Pulmonary function testing was conducted on volunteers recruited from 4 community centers in Xi'an, China, between July and August 2012. Participants underwent 3 FVC maneuvers. The maneuver with the best FEV1 was retained. FVC, FEV1, and FEV6 were measured by portable spirometer. The receiver operating characteristic curves that corresponded to the optimal combination of sensitivity and specificity for FEV1/FEV6 were determined. A kappa test was used to compare the agreement between FEV1/FVC and FEV1/FEV6. The positive predictive value and negative predictive value were also calculated.\", 'A total of 767 volunteers participated in this study, of whom 297 were male and 470 were female. Considering FEV1/FVC <0.70 as the accepted standard for COPD, the area under the curve was 98% (P < .001), and the FEV1/FEV6 cutoff, corresponding to the greatest sum of sensitivity and specificity, was 0.72. For the total population, the FEV1/FEV6 sensitivity, specificity, positive predictive value, and negative predictive value were 96.9, 98.8, 95.8, and 99.2%, respectively. The agreement between the 2 cutoff points was excellent, and the kappa value was 0.954.",
            "output": [
                "Does fEV1/FEV6 in Primary Care be a Reliable and Easy Method for the Diagnosis of COPD?"
            ]
        },
        {
            "id": "task847-04e0a58ace524362801153accbdb4e1b",
            "input": "To evaluate the current evidence of the relationship between myopia, together with its structural and refractive component, and diabetic retinopathy (DR) risk.', \"A systematic search was performed up to April, 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated employing random-effects models. Three models were used to assess the association between myopia and risk of DR: axial length (AL) (per millimetre increase) and DR; myopia (myopia versus non-myopia) and DR; refractive error (RE) (per D decrease) and DR. Publication bias of the literature was evaluated using Begg's funnel plots and Egger's test.\", 'A total of 11 studies that met the predefined criteria were included in this meta-analysis. Overall, longer AL (per millimetre increase) was associa-ted with a significantly decreased risk of DR (combined OR, 0.75; 95% CI, 0.65-0.86; p\\xa0<\\xa00.001); myopic eyes (myopia versus non-myopia) showed a lower risk of DR (combined OR, 0.70; 95% CI, 0.58-0.85; p\\xa0<\\xa00.001). A greater degree of myopic RE (per D decrease) also revealed a significantly decreased risk of DR (combined OR, 0.89; 95% CI, 0.85-0.93; p\\xa0<\\xa00.001). The sensitivity analyses and cumulative meta-analysis showed similar results. No publication bias was detected in any of the three models.",
            "output": [
                "Are myopia and/or longer axial length protective against diabetic retinopathy : a meta-analysis?"
            ]
        },
        {
            "id": "task847-ceabdca66d43462196b0d29a95902435",
            "input": "The overall aim of this study was to evaluate how supplementation of chondrocyte media with recombinant acid ceramidase (rhAC) influenced cartilage repair in a rat osteochondral defect model.', 'Primary chondrocytes were grown as monolayers in polystyrene culture dishes with and without rhAC (added once at the time of cell plating) for 7 days, and then seeded onto Bio-Gide\u00ae collagen scaffolds and grown for an additional 3 days. The scaffolds were then introduced into osteochondral defects created in Sprague-Dawley rat trochlea by a microdrilling procedure. Analysis was performed 6 weeks post-surgery macroscopically, by micro-CT, histologically, and by immunohistochemistry.', 'Treatment with rhAC led to increased cell numbers and glycosaminoglycan (GAG) production (\u223c2 and 3-fold, respectively) following 7 days of expansion in vitro. Gene expression of collagen 2, aggrecan and Sox-9 also was significantly elevated. After seeding onto Bio-Gide\u00ae, more rhAC treated cells were evident within 4 h. At 6 weeks post-surgery, defects containing rhAC-treated cells exhibited more soft tissue formation at the articular surface, as evidenced by microCT, as well as histological evidence of enhanced cartilage repair. Notably, collagen 2 immunostaining revealed greater surface expression in animals receiving rhAC treated cells as well. Collagen 10 staining was not enhanced.",
            "output": [
                "Does acid ceramidase treatment enhance the outcome of autologous chondrocyte implantation in a rat osteochondral defect model?"
            ]
        },
        {
            "id": "task847-48fc8cf68ea3448385928a32041eaa9e",
            "input": "We have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. This study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring.\", 'On gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. Terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother.', 'Pups born from high-fat hypercaloric diet (HFD) dams developed metabolic abnormalities persistent throughout development. Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern. Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. Furthermore, HFD dams delivered pups prone to develop more severe disease after respiratory syncytial virus (RSV) infection.",
            "output": [
                "Does maternal high-fat hypercaloric diet during pregnancy result in persistent metabolic and respiratory abnormalities in offspring?"
            ]
        },
        {
            "id": "task847-f8ad4943ab984a49abc9087e75bc039b",
            "input": "Substance P (SP), neurokinin-1 receptors (NK-1Rs) are expressed in mesenteric preadipocytes and SP binding activates proinflammatory signalling in these cells. We evaluated the expression levels of SP (Tac-1), NK-1R (Tacr-1), and NK-2R (Tacr-2) mRNA in preadipocytes isolated from patients with Inflammatory Bowel Disease (IBD) and examined their responsiveness to SP compared to control human mesenteric preadipocytes. The Aim of our study is to investigate the effects of the neuropeptide SP on cytokine expression in preadipocytes of IBD vs control patients and evaluate the potential effects of these cells on IBD pathophysiology via SP-NK-R interactions.', \"Mesenteric fat was collected from control, Ulcerative colitis (UC) and Crohn's disease (CD) patients (n=10-11 per group). Preadipocytes were isolated, expanded in culture and exposed to substance P. Colon biopsies were obtained from control and IBD patients.\", 'Tacr-1 and -2 mRNA were increased in IBD preadipocytes compared to controls, while Tac-1 mRNA was increased only in UC preadipocytes. SP differentially regulated the expression of inflammatory mediators in IBD preadipocytes compared to controls. Disease-dependent responses to SP were also observed between UC and CD preadipocytes. IL-17A mRNA expression and release increased after SP treatment in both CD and UC preadipocytes, while IL-17RA mRNA increased in colon biopsies from IBD patients.",
            "output": [
                "Does substance P mediate pro-inflammatory cytokine release form mesenteric adipocytes in Inflammatory Bowel Disease patients?"
            ]
        },
        {
            "id": "task847-edbc379de2b447b486586c1394ccbf13",
            "input": "Proper selection of patients for carotid artery stenting (CAS) remains controversial despite multiple controlled trials. This relates in part to differences in interpretation of the relative importance of myocardial vs stroke complications after the procedure by different specialties and a lack of granular clinical data to analyze outcomes outside the large clinical trials. The objective of this study was to assess the effect of preoperative medications, procedure parameters, and patient characteristics on outcomes of CAS performed in a multispecialty national database.', 'We analyzed all patients who underwent CAS between 2005 and 2014 in the Vascular Quality Initiative. A multivariate logistic regression model was built to assess the effects of age, gender, comorbidities, smoking, preprocedure medications, procedure details, and hypotension or hypertension that required intravenous medication on 30-day death or stroke rates.', 'A total of 5263 patients underwent CAS (mean age, 70 years; 63% male). The 30-day stroke/death rate was 3.4% (1.5% minor stroke, 0.9% major stroke, and 1.2% death; 40% of patients who had major strokes died within 30 days), and the myocardial infarction rate was 0.8%. Postprocedural hypertension requiring treatment occurred in 519 cases (9.9%), and it was associated with a 3.4-fold increase in stroke/death (odds ratio, 3.39; 95% confidence interval, 2.30-5.00; P < .0001). Preprocedural beta-blocker use for >30 days was associated with a 34% reduction in the stroke/death risk (odds ratio, 0.66; 95% confidence interval, 0.46-0.95; P = .025) compared with nonuse. Beta-blocker use was not associated with postprocedural hypotension. Other predictors of postoperative stroke and death included age, symptomatic status, diabetes (type 1 or type 2), and postprocedural hypotension, whereas prior carotid endarterectomy and distal embolic protection use were protective.",
            "output": [
                "Is beta-blocker use associated with lower stroke and death after carotid artery stenting?"
            ]
        },
        {
            "id": "task847-f12af51440c04a179693c691021bf41d",
            "input": "To discuss the protective mechanisms of atorvastatin treatment for isoproterenol (ISO)-induced chronic heart failure.', 'The rats were randomly divided into three groups: normal group (n = 15, age-matched normal adult rats), ISO group (n = 11, ISO induced heart failure) and atorvastatin group (n = 14, ISO induced lesion but received atorvastatin treatment). The cardiac function was evaluated by echocardiography and hemodynamics analysis. In addition, the Rac1 activity in the myocardium and the expression levels of Rac1, p47phox and p67phox were measured by RT-PCR and western blot.', 'Rats in ISO group developed into heart failure with decreased cardiac function. The Rac1, p47phox and p67phox mRNA expressions and ROS release were increased in ISO group. Atorvastatin treatment improved cardiac function of rats with isoproterenol-induced chronic heart failure and decreased the Rac1, p47phox and p67phox mRNA expressions. Also, membrane protein expression of Rac1 and ROS release decreased significantly.",
            "output": [
                "Does atorvastatin improve cardiac function of rats with chronic cardiac failure via inhibiting Rac1/P47phox/P67phox-mediated ROS release?"
            ]
        },
        {
            "id": "task847-7408f4fe9ab340e7883f62983897e4e8",
            "input": "Insomnia increases in prevalence with age, is strongly associated with depression, and has been identified as a risk factor for suicide in several studies. The aim of this study was to determine whether insomnia severity varies between those who have attempted suicide (n = 72), those who only contemplate suicide (n = 28), and those who are depressed but have no suicidal ideation or attempt history (n = 35).', 'Participants were middle-aged and older adults (age 44-87, M = 66 years) with depression. Insomnia severity was measured as the sum of the early, middle, and late insomnia items from the Hamilton Rating Scale for Depression. General linear models examined relations between group status as the independent variable and insomnia severity as the dependent variable.', 'The suicide attempt group suffered from more severe insomnia than the suicidal ideation and non-suicidal depressed groups (p < 0.05). Differences remained after adjusting for potential confounders including demographics, cognitive ability, alcohol dependence in the past month, severity of depressed mood, anxiety, and physical health burden. Moreover, greater insomnia severity in the suicide attempt group could not be explained by interpersonal difficulties, executive functioning, benzodiazepine use, or by the presence of post-traumatic stress disorder.",
            "output": [
                "Is insomnia associated with suicide attempt in middle-aged and older adults with depression?"
            ]
        },
        {
            "id": "task847-d8d57f1f08644fba8a05330e88a68faa",
            "input": "The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery.', 'The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1 = 16th-20th weeks, T2 = 26th-30th weeks and T3 = at delivery). Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology.', 'Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B12 levels were significantly higher in PE (p < 0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p < 0.05 for both) and T3 (p < 0.01).",
            "output": [
                "Do increased homocysteine levels exist in women with preeclampsia from early pregnancy?"
            ]
        },
        {
            "id": "task847-41755616048846a3b2e311935804bd97",
            "input": "Small intestinal bacterial overgrowth is encountered in bowel disorders, including irritable bowel symptoms. Low degrees of inflammation have been recently reported in the irritable bowel syndrome. We looked for the association between intestinal inflammation and small intestinal bacterial overgrowth in irritable bowel syndrome.', 'Small intestinal bacterial overgrowth was assessed by the H2 glucose breath test in 90 consecutive patients with irritable bowel syndrome. A check-up of the oral cavity was carried out before the breath testing. Further on, the patients were classified into two groups, positive and negative, at the breath test. Then they were tested for intestinal inflammation with a fecal test for calprotectin. We used a semiquantitative test for this study. Both groups were compared for the association of intestinal inflammation with small intestinal bacterial overgrowth.', 'A number of 24/90 (26.7%) patients with irritable bowel syndrome had small intestinal bacterial overgrowth. A positive test for intestinal inflammation was significantly more frequent in patients with irritable bowel syndrome and small intestinal bacterial overgrowth (chi(2): p<0.05).",
            "output": [
                "Is small Intestinal Bacterial Overgrowth Associated with Intestinal Inflammation in the Irritable Bowel Syndrome?"
            ]
        },
        {
            "id": "task847-be7af169b7f94666bda02e32365a8e56",
            "input": "Anal intraepithelial neoplasia precedes the development of anal squamous cell carcinoma. Detection of the lesion is essential to management. This paper describes a prospective study to detect and ablate anal squamous intraepithelial lesions (SILs) using white light narrow band imaging (NBI) and NBI with acetic acid (NBIA).', 'Sixty patients with abnormal anal cytology and risk factors for anal dysplasia underwent examination of the anoderm with a high definition gastroscope and NBIA. Targeted biopsies were taken and the lesions were ablated and characterized histopathologically. Visualization of the anal transitional zone was facilitated by retroflexion and examination through a disposable anoscope.', 'Targeted biopsies were taken from lesions in 58 patients. No lesion was seen in two patients. Histopathology showed SIL in 48 (80.0%) of 60 biopsies. One biopsy showed lymphoid aggregates. Biopsies in nine (15%) of the 60 patients showed normal mucosa. Lesions were seen in white light in 27 (45%) of the 60 cases, NBI in 39 (65%) and NBIA in 57 (95%). There was no major morbidity. Sensitivity analysis showed that all methods were significantly different from each other.",
            "output": [
                "Is detection of anal dysplasia enhanced by narrow band imaging and acetic acid?"
            ]
        },
        {
            "id": "task847-fad998d5f7b143ae9e454a514b850701",
            "input": "The progression of pathological left ventricular remodelling leads to cardiac dysfunction and contributes to the occurrence of malignant arrhythmias and sudden cardiac death. The underlying molecular mechanisms remain unclear, however. Our aim was to examine the role of the renin-angiotensin system (RAS) in the mechanism underlying arrhythmogenic cardiac remodelling using a transgenic mouse expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). This mouse model exhibits progressive cardiac dysfunction leading to lethal arrhythmias.', 'Subcutaneous administration of aliskiren, a direct renin inhibitor, significantly suppressed the progression of pathological cardiac remodelling and improved survival among dnNRSF-Tg mice while reducing arrhythmogenicity. Genetic deletion of the angiotensin type 1a receptor (AT1aR) similarly suppressed cardiac remodelling and sudden death. In optical mapping analyses, spontaneous ventricular tachycardia (VT) and fibrillation (VF) initiated by breakthrough-type excitations originating from focal activation sites and maintained by functional re-entry were observed in dnNRSF-Tg hearts. Under constant pacing, dnNRSF-Tg hearts exhibited markedly slowed conduction velocity, which likely contributes to the arrhythmogenic substrate. Aliskiren treatment increased conduction velocity and reduced the incidence of sustained VT. These effects were associated with suppression of cardiac fibrosis and restoration of connexin 43 expression in dnNRSF-Tg ventricles.",
            "output": [
                "Does the renin-angiotensin system promote arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy?"
            ]
        },
        {
            "id": "task847-343812654e3e4fffb24efcb23ec18be7",
            "input": "Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, morphologically diverse, \"aggressive variant prostate cancer (AVPC)\" also share molecular features with SCPC.', 'Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC.', 'Irrespective of morphology, Ki67 and Tp53 stained \u226510% cells in 80% and 41% of samples, respectively. RB1 stained <10% cells in 61% of samples and AR in 36%. MYC (surrogate for 8q) CNG and RB1 CNL showed in 54% of 44 samples each and PTEN CNL in 48%. All but 1 of 8 PDX bore Tp53 missense mutations. RB1 CNL was the strongest discriminator between unselected castration-resistant prostate cancer (CRPC) and the AVPC. Combined alterations in RB1, Tp53, and/or PTEN were more frequent in the AVPC than in unselected CRPC and in The Cancer Genome Atlas samples.",
            "output": [
                "Do combined Tumor Suppressor Defects Characterize Clinically Defined Aggressive Variant Prostate Cancers?"
            ]
        },
        {
            "id": "task847-c938c65c44e5426da985626ccb9e9acb",
            "input": "International registries for acute type A aortic dissection (TAAD) demonstrate stagnant operative mortality rates in excess of 20% and stroke rates of 9% to 25%, with little global emphasis on stroke reduction or carotid involvement. Cerebral malperfusion with TAAD has been linked to poorer outcome. We hypothesize that concomitant carotid dissection or complex dissection flaps in the arch play a major role in stroke development and that aggressive reconstruction of the arch and carotid arteries can improve neurologic outcomes in TAAD.', 'A standardized protocol focused on expedient care, neurocerebral protection, and common carotid and total arch reconstruction was developed for 264\\xa0consecutive TAADs. Arch and complete carotid replacement was based on arch dissection anatomy, carotid involvement, or an intraarch tear. Neurocerebral monitoring with continuous electroencephalogram/somatosensory evoked potentials was used in all cases.', 'The postoperative stroke and hospital mortality rates were 3.4% and 9.1%, and stroke rates by extent of arch replacement were 4%, 3%, and 0% for hemiarch, total arch, and total arch with complete carotid replacement, respectively. An intraoperative change in the electroencephalogram/somatosensory evoked potentials was strongly predictive of stroke and had a negative predictive value of 98.2%.",
            "output": [
                "Does aggressive Aortic Arch and Carotid Replacement Strategy for Type A Aortic Dissection improve Neurologic Outcomes?"
            ]
        },
        {
            "id": "task847-c3ad86ddb7074a689ca211b5d20581cf",
            "input": "Activation of the transcription factor NF-\u03baB and expression of pro-inflammatory mediators have been considered as major events of acute pancreatitis (AP). Karyopherin alpha 2 (KPNA2), a member of the importin \u03b1 family, reportedly modulates p65 subcellular localization.', 'This study aimed to investigate the expression and possible functions of KPNA2 in the AP cell and animal model, focusing on its association with NF-\u03baB activation.', 'An AP cell model was established with the cerulein-stimulated AR42J and isolated rat pancreatic acinar cells. The AP rat model was induced by the intraperitoneal injection of cerulein. The secretion of TNF-\u03b1, IL-6, and LDH was detected by ELISA kits and the production of NO using nitric oxide kit. Expression of KPNA2 was measured by RT-PCR and Western blot. Expression levels of IKK\u03b1, phosphorylation of p65, and total p65 were detected by Western blot. Co-localization of KPNA2 with p65 was observed by immunofluorescence assay. To determine the biological functions of KPNA2 in cerulein-induced inflammatory response, RNA interference was employed to knockdown KPNA2 expression in AR42J and isolated pancreatic acini cells.', 'Cerulein stimulated KPNA2 expression and IL-6, TNF-\u03b1, NO, and LDH production in rat pancreatic acinar cells. Cerulein triggered the phosphorylation and nuclear translocation of NF-\u03baB p65 subunit, indicating the NF-\u03baB activation. The co-localization and nuclear accumulation of KPNA2 and p65 were detected in cerulein-treated cells. Knocking down KPNA2 hindered cerulein-induced nuclear transportation of p65 and alleviated the subsequent inflammatory response in rat pancreatic acinar cells. Additionally, KPNA2 expression was significantly up-regulated in cerulein-induced AP rat model.",
            "output": [
                "Does karyopherin Alpha 2 promote the Inflammatory Response in Rat Pancreatic Acinar Cells Via Facilitating NF-\u03baB Activation?"
            ]
        },
        {
            "id": "task847-21dd66a7a5494eb99ca5f905fd6755ae",
            "input": "Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population.', 'To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States.', 'The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar.', 'Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness.', 'Myocardial scar detected by CMR imaging.', 'Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91; P <\\u2009.001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17; P <\\u2009.001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61, P =\\u2009.005); for hypertension: OR, 1.61 (95% CI, 1.12-2.30; P =\\u2009.009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28; P =\\u2009.006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (P \u2264 .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (C statistic, 0.81 with CAC vs 0.79 without CAC, P =\\u2009.01).",
            "output": [
                "Does prevalence and correlate of Myocardial Scar in a US Cohort?"
            ]
        },
        {
            "id": "task847-161d7d157e7e494980d5a6809dc5ea62",
            "input": "To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) gliosis is associated with obesity and insulin resistance in humans.', 'Sixty-seven participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH gliosis (N\\u2009=\\u200922) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N\\u2009=\\u200923) from the lowest tertile. In a separate postmortem study, brain slices (N\\u2009=\\u200910) through the MBH were imaged by MRI and stained for glial fibrillary acidic protein (GFAP).', 'In all participants, longer T2 relaxation time in the left MBH was associated with higher BMI (P\\u2009=\\u20090.01). Compared with controls, cases had longer T2 relaxation times in the right MBH (P\\u2009<\\u20090.05), as well as higher BMI (P\\u2009<\\u20090.05), fasting insulin concentrations (P\\u2009<\\u20090.01), and HOMA-IR values (P\\u2009<\\u20090.01), adjusted for sex and age. Elevations in insulin and HOMA-IR were also independent of BMI. In the postmortem study, GFAP staining intensity was positively associated with MBH T2 relaxation time (P\\u2009<\\u20090.05), validating an MRI-based method for the detection of MBH gliosis in humans.",
            "output": [
                "Is radiologic evidence that hypothalamic gliosis associated with obesity and insulin resistance in humans?"
            ]
        },
        {
            "id": "task847-f713541b928647ceb55161e34efd6a98",
            "input": "The present meta-analysis aimed to investigate whether there is an association between SERPINE1 rs1799768 polymorphism and sepsis risk and mortality.', 'Published reports were searched in PubMed, PubMed Central, Gene, PubChem and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed in a random-effects model.', 'The results of the overall meta-analysis indicated that an increased sepsis risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.30; 95% CI 1.08-1.56; p = 0.006). When studies were stratified by ethnicity, no significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk in the Asian group. As for the Caucasian population, overall OR was 1.24 (95% CI 1.02-1.51; p = 0.03). The results of the overall meta-analysis indicated that an increased sepsis mortality risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.73; 95% CI 1.31-2.28; p < 0.0001). When studies were stratified by ethnicity, significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk mortality in the Asian group and the Caucasian population.",
            "output": [
                "Does sERPINE1 rs1799768 polymorphism contribute to sepsis risk and mortality?"
            ]
        },
        {
            "id": "task847-efdaf374fd784b01b757c18260932ac8",
            "input": "Determining the reasons people choose to study nursing may help educators and managers develop student-focussed and enticing nursing programmes. In Australia, little research has been undertaken with students entering nursing programmes and the reasons for their choice.', 'The aim of this study was to determine why new students choose to enter nursing at university.', 'A descriptive survey design.', 'An urban university in Sydney, Australia.', 'Undergraduate nursing students at the beginning of their first year of study.', \"An open-ended question relating to the reasons for students' choice of a nursing programme was included in the survey. The transcribed textual data were content analysed for words related to the students' choice.\", \"The students' reasons for entering nursing programmes were both personal and career related, with personal being more dominant. The reasons to start nursing were: being able to help and care for people, job security, the ability to enter tertiary education and the enjoyment or love of nursing.",
            "output": [
                "Do the reasons students choose to undertake a nursing degree?"
            ]
        },
        {
            "id": "task847-da55e79eb89b4750acf36d8527d43522",
            "input": "To identify subgroups of patients with renal stones \u226520 mm that are more suitable for extracorporeal shock wave lithotripsy (ESWL) monotherapy.', 'A total of 376 patients with renal stones \u226520 mm underwent monotherapy with ESWL. The treatment outcome was evaluated after 3 months of follow-up. A stone-free status or fragmentation of stones to 4 mm or smaller was considered efficacious.', 'At 3 months after treatment, the overall stone-free rate was 64.4%, and the efficacy rate was 70.7%. The efficacy rate was 89.4% for patients with a residual stone surface area \u226450% of baseline after the first ESWL, while the efficacy rate was 32.4% for other patients. The efficacy was 92.2% for stones \u2264400 mm2 and those with lower radiodensity, as determined by a plain (KUB) film.",
            "output": [
                "Do treatment of Renal Stones \u226520 mm with Extracorporeal Shock Wave Lithotripsy?"
            ]
        },
        {
            "id": "task847-b062e7746dbe418faf101751914666c8",
            "input": "Patients with missed colorectal cancer have been reported to be more likely to have colonic diverticulosis. Such an association could be due to either higher risk of neoplasia or difficulty examining the colon in patients with diverticulosis. The aim of this study was to determine whether colonic diverticula are associated with an increased risk for colonic neoplasia.', 'We analyzed data from a prospective study of patients undergoing screening colonoscopy that included detailed assessment of all colonic diverticula and colorectal polyps. We used logistic regression to estimate odds ratios and 95% confidence intervals while adjusting for confounding variables.', 'Our analyses included 624 participants. Of these, 216 (35%) had one or more colorectal adenomas. Diverticula on colonoscopy were not associated with an increased risk of adenomas (odds ratio (OR) 1.0, 95% confidence interval (CI) 0.7-1.4) or advanced adenomas (OR 0.8, 95% CI 0.4-1.5). Those with the greatest burden of diverticula (10 or more) did not have an increased risk of adenomas (OR 1.1, 95% CI 0.7-1.8) compared with no diverticula. Colonic diverticula were not associated with an increased risk of proximal (OR 1.0, 95% CI 0.6-1.6) or distal adenomas (OR 1.0, 95% CI 0.6-1.7).",
            "output": [
                "Are colonic Diverticula Associated With an Increased Risk of Colorectal Adenomas?"
            ]
        },
        {
            "id": "task847-756e231600024fbaa123609840cd22ca",
            "input": "Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance. To overcome this clinical obstacle, our goal was to identify inhibitors with improved potency that can target intractable ALK variants such as F1174L. We find that PF-06463922 has high potency across ALK variants and inhibits ALK more effectively than crizotinib in vitro. Most importantly, PF-06463922 induces complete tumor regression in both crizotinib-resistant and crizotinib-sensitive xenograft mouse models of neuroblastoma, as well as in patient-derived xenografts harboring the crizotinib-resistant F1174L or F1245C mutations. These studies demonstrate that PF-06463922 has the potential to overcome crizotinib resistance and exerts unprecedented activity as a single targeted agent against F1174L and F1245C ALK-mutated xenograft tumors, while also inducing responses in an R1275Q xenograft model. Taken together, these results provide the rationale to move PF-06463922 into clinical trials for treatment of patients with ALK-mutated neuroblastoma.",
            "output": [
                "Does the ALK/ROS1 Inhibitor PF-06463922 overcome Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma?"
            ]
        },
        {
            "id": "task847-4d073220676645f09f3916a3247f6069",
            "input": "We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress.', 'Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P\\xa0=\\xa05.69E-07) and 69% (P\\xa0=\\xa02.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P\\xa0=\\xa07.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P\\xa0=\\xa02.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P\\xa0=\\xa05.11E-06) in the aorta.",
            "output": [
                "Does plasmalogen modulation attenuate atherosclerosis in ApoE- and ApoE/GPx1-deficient mice?"
            ]
        },
        {
            "id": "task847-13fcab99e8b4415e8d0011907d1671b7",
            "input": "In this study, we examined chondrogenic regulation of 2 types of mesenchymal stem cells seeded on the bioengineered substrate in monolayer cultures under mechanically defined conditions to mimic the in vivo microenvironment of chondrocytes within articular cartilage tissues.', 'Human adipose-derived mesenchymal stem cells (ASCs) and bone marrow mesenchymal stem cells (BSCs) were exposed to 0.2 Pa shear stress, 3 MPa cyclic hydrostatic pressure, and combined loading with different sequences on chemically designed medical-grade silicone rubber, while no soluble growth factors were added to the culture medium. The expression levels of chondrogenic-specific genes of SOX9, aggrecan, and type II collagen (Col II) were measured. Results were compared to those of cells treated by biological growth factor.', 'Gene expression patterns were dependent on the loading regime. Moreover, the source of mesenchymal stem cells (adipose or bone marrow) was influential in gene expression. Overall, enhanced expression of chondrogenic markers was found through application of mechanical stimuli. The response was generally found to be significantly promoted when the 2 loading regimes were superimposed.",
            "output": [
                "Do the synergistic effects of shear stress and cyclic hydrostatic pressure modulate chondrogenic induction of human mesenchymal stem cells?"
            ]
        },
        {
            "id": "task847-8cca592e63294d48b54a92a09a9f09dd",
            "input": "Periprosthetic osteolysis, involving RANK/RANKL/osteoprotegerin (OPG) and TNF-\u03b1/NF\u03baB signaling, contributes to bone resorption and inflammation. We constructed lentivirus vectors to inhibit TNF-\u03b1 and enhance OPG expression and assessed their impacts on wear debris-induced inflammation and osteoclastogenesis in an osteoclast/osteoblast coculture system.', 'We transduced mouse osteoblastic MC3T3-E1 cells with Lenti-negative control (Lenti-NC), Lenti-OPG or Lenti-siTNF\u03b1-OPG, and murine macrophage/monocyte RAW264.7 cells with Lenti-NC, Lenti-TNF-\u03b1 siRNA or Lenti-siTNF\u03b1-OPG. Then, TNF-\u03b1 and OPG protein levels were evaluated by enzyme-linked immunosorbent assay. We cocultured transduced MC3T3-E1 and RAW264.7 cells in transwell chambers in the presence of 0.1 mg/mL Ti particles to investigate the capacity of TNF-\u03b1 inhibition to reduce wear debris-induced inflammation. We also assessed mRNA levels TNF-\u03b1, IL-1\u03b2, IL-6 and OPG by RT-PCR as well as osteoclastogenesis by tartrate-resistant acid phosphatase.', 'Lenti-siTNF\u03b1-OPG ameliorated Ti-particle-induced expression of TNF-\u03b1, IL-1\u03b2, IL-6 in MC3T3-E1/RAW264.7 cocultures, while enhancing mRNA and protein levels of OPG, and reducing the fraction of tartrate-resistant acid phosphatase (TRAP)+ cells.",
            "output": [
                "Does tNF-\u03b1 suppression and osteoprotegerin overexpression inhibit wear debris-induced inflammation and osteoclastogenesis in vitro?"
            ]
        },
        {
            "id": "task847-b414733cd3ad4f48b095154bf20694ca",
            "input": "The serotonin release assay (SRA) is considered the gold standard laboratory test for heparin-induced thrombocytopenia (HIT). The historic SRA method uses platelets loaded with radiolabeled serotonin to evaluate platelet activation by HIT immune complexes. However, a nonradioactive method is desirable. We report the performance characteristics of a high-performance liquid chromatography (HPLC) SRA method.', 'We validated the performance characteristics of an HPLC-SRA method, including correlation with a reference laboratory using the radioactive method. Serotonin released from reagent platelets was quantified by HPLC using fluorescent detection. Results were expressed as % release and classified as positive, negative, or indeterminate based on previously published cutoffs.', 'Serum samples from 250 subjects with suspected HIT were tested in the HPLC-SRA and with the radioactive method. Concordant classifications were observed in 230 samples (92%). Sera from 41 healthy individuals tested negative. Between-run imprecision studies showed standard deviation of <6 (% release) for positive, weak positive, and negative serum pools. Stability studies demonstrated stability after two freeze-thaw cycles or up to a week of refrigeration.",
            "output": [
                "Is a high-performance liquid chromatography method for the serotonin release assay equivalent to the radioactive method?"
            ]
        },
        {
            "id": "task847-1c6172673d4a41219a2a51653fac1170",
            "input": "Hyperinflammation is a hallmark feature of cystic fibrosis (CF) airways. However, inflammation has also been documented systemically and, more recently, in extrapulmonary CF-affected tissues such as the pancreas and intestine. The pathogenesis of CF-related inflammation and more specifically the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in that respect are not entirely understood. We have tested the hypothesis that genetic depletion of CFTR will affect the inflammatory status of human intestinal epithelial cell lines.', 'CFTR expression was genetically depleted from Caco-2/15 and HT-29 cells using short hairpin RNA interference (shRNAi). Inflammatory conditions were induced by the addition of human recombinant tumor necrosis factor (TNF) or Interleukin-1\u03b2 (IL-1\u03b2) for various periods of time. Gene expression, mRNA stability and secreted levels of interleukin (IL)-6, -8 and 10 were assessed. Analysis of pro- and anti-inflammatory signaling pathways including mitogen-activated protein kinases (p38, ERK 1/2 and JNK), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (I\u03baB\u03b1), and nuclear factor-kappa B (NF-\u03baB) was also performed. Eosinophils were counted in the jejunal mucosa of Cftr-/- and Cftr+/+ mice.', 'CFTR gene and protein knockdown caused a significant increase in basal secretion of IL-8 as well as in IL-1\u03b2-induced secretion of IL-6 and -8. Release of the anti-inflammatory cytokine, IL-10, remained unaffected by CFTR depletion. The enhanced secretion of IL-8 stems in part from increased IL8 mRNA levels and greater activation of ERK1/2 MAPK, I\u03baB\u03b1 and NF-\u03baB in the CFTR knockdown cells. By contrast, phosphorylation levels of p38 and JNK MAPK did not differ between control and knockdown cells. We also found a higher number of infiltrating eosinophils in the jejunal mucosa of Cftr -/- females, but not males, compared to Cftr +/+ mice, thus providing in vivo support to our in vitro findings.",
            "output": [
                "Does cFTR Knockdown induce proinflammatory changes in intestinal epithelial cells?"
            ]
        },
        {
            "id": "task847-99d60452175e4aeda343fbfa6412ef54",
            "input": "Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR).', 'A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR.', 'Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p\\u2009=\\u20090.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p\\u2009=\\u20090.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p\\u2009<\\u20090.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively, p\\u2009<\\u20090.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p\\u2009<\\u20090.001).",
            "output": [
                "Are sarcopenia and inflammation independent predictors of survival in male patients newly diagnosed with small cell lung cancer?"
            ]
        },
        {
            "id": "task847-804a72a3e64d49489da79d850f2ab46b",
            "input": "Matrix metalloproteinases (MMPs) have a central role in compromising the integrity of the blood-brain barrier (BBB). The role of MMP-12 in brain damage after ischemic stroke remains unknown. The main objective of the current study is to investigate the effect of MMP-12 suppression at an early time point before reperfusion on the BBB damage in rats.', 'Sprague-Dawley rats were subjected to middle cerebral artery occlusion and reperfusion. MMP-12 shRNA-expressing plasmids formulated as nanoparticles were administered at a dose of 1 mg/kg body weight. The involvement of MMP-12 on BBB damage was assessed by performing various techniques, including Evans blue dye extravasation, 2,3,5-triphenyltetrazolium chloride staining, immunoblot, gelatin zymography, and immunofluorescence analysis.', 'MMP-12 is upregulated \u224831-, 47-, and 66-fold in rats subjected 1-, 2-, or 4-hour ischemia, respectively, followed by 1-day reperfusion. MMP-12 suppression protected the BBB integrity by inhibiting the degradation of tight-junction proteins. Either intravenous or intra-arterial delivery of MMP-12 shRNA-expressing plasmid significantly reduced the percent Evans blue dye extravasation and infarct size. Furthermore, MMP-12 suppression reduced the endogenous levels of other proteases, such as tissue-type plasminogen activator and MMP-9, which are also known to be the key players involved in BBB damage.",
            "output": [
                "Does matrix Metalloproteinase-12 induce Blood-Brain Barrier Damage After Focal Cerebral Ischemia?"
            ]
        },
        {
            "id": "task847-a94cd9d1870d4cb5a4cba4159d67617b",
            "input": "To assess quantitatively the influence of rotigotine transdermal patch on daytime sleepiness, the most common adverse event by non-ergot dopamine agonists (DAs), in Parkinson disease (PD) patients.', 'An open-label study enrolled PD patients with unsatisfactory control of motor symptoms. Treatment with rotigotine transdermal patch was titrated to optimal dose (4-8 mg/24 hours) over 2 to 4 weeks. Primary outcome was Epworth Sleepiness Scale (ESS) for daytime sleepiness. Secondary outcomes included Hoehn&Yahr stage, time spent with dyskinesia, Clinical Global Impression of Improvement (CGI-I) of motor symptoms, adverse events, and compliance.', 'The subjects were 31 PD patients (age 72 \u00b1 8, Hoehn &Yahr stage 2.7 \u00b1 0.9, mean \u00b1 SD). The ESS did not increase after rotigotine treatment (7.2 \u00b1 4.9 before treatment, 6.2 \u00b1 4.0 with 4 mg/24 hour, and 8.1 \u00b1 6.4 with 8 mg/24 hour). The CGI-I score improved after treatment; responder rate reached 88.9% with 8 mg/24 hours. No patients showed worsening in other secondary outcomes. In 13 patients treated with equivalent doses of rotigotine switched from other DAs (pramipexole, ropinirole, and cabergoline), ESS did not increase after treatment (10.0 \u00b1 4.6 before and 8.6 \u00b1 4.5 after treatment) and decreased without worsening of CGI-I in 54% patients. Other secondary outcomes did not worsen after treatment.",
            "output": [
                "Does rotigotine Transdermal Patch Make Parkinson Disease Patients Sleepy During Daytime?"
            ]
        },
        {
            "id": "task847-114dd8b30af744c7b0bda13052202aac",
            "input": "After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk.', 'A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease.', \"Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9\\xa0\u03bcmol/L; p\\xa0<\\xa00.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980\\xa0\u03bcmol/L; p\\xa0=\\xa00.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43\\xa0\u03bcmol/L; p\\xa0=\\xa00.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho:\\xa0-0.281; p\\xa0<\\xa00.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8\\xa0\u03bcmol/L; p\\xa0=\\xa00.045).",
            "output": [
                "Are plasma levels of trimethylamine-N-oxide confounded by impaired kidney function and poor metabolic control?"
            ]
        },
        {
            "id": "task847-d7e3162dfa9b4b45b1c218a505eeb553",
            "input": "Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS.', 'Here we applied 6h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5days. We investigated the \"micro-lesion\" effect by using a sham stimulation group (8 mice) and a control group (8 mice with a hole drilled into the skull only). Whole brain anatomy was investigated post-mortem using high-resolution magnetic resonance imaging and areas demonstrating volumetric expansion were further investigated using histology and immunohistochemistry.', 'The DBS group demonstrated bilateral increases in whole hippocampus and the left thalamus volume compared to both sham and control groups. Local hippocampal and thalamic volume increases were also observed at the voxel-level; however these increases were observed in both DBS and sham groups. Follow-up immunohistochemistry in the hippocampus revealed DBS increased blood vessel size and synaptic density relative to the control group whereas the sham group demonstrated increased astrocyte size.",
            "output": [
                "Does deep brain stimulation of the ventromedial prefrontal cortex cause reorganization of neuronal processes and vasculature?"
            ]
        },
        {
            "id": "task847-a24d46ebe6ea4131ad4c433dc5a7d228",
            "input": "RpfB is a key factor in resuscitation from dormancy of Mycobacterium tuberculosis. This protein is a cell-wall glycosidase, which cleaves cell-wall peptidoglycan. RpfB is structurally complex and is composed of three types of domains, including a catalytic, a G5 and three DUF348 domains. Structural information is currently limited to a portion of the protein including only the catalytic and G5 domains. To gain insights into the structure and function of all domains we have undertaken structural investigations on a large protein fragment containing all three types of domains that constitute RpfB (RpfB3D).', 'The structural features of RpfB3D have been investigated combining x-ray crystallography and biophysical studies.",
            "output": [
                "Does the structure of Resuscitation promoting factor B from M. tuberculosis reveal unexpected ubiquitin-like domains?"
            ]
        },
        {
            "id": "task847-ae6d697dca2b4ebe84c659ede5e6fa96",
            "input": "Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main \u03b1-secretase preventing beta-amyloid (\u03b2A) formation.\", 'Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using \u03b2-actin as endogenous control.', 'Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication.",
            "output": [
                "Do serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-cd939261c9ec4861ad859082ea4ee8ca",
            "input": "Injuries to runners are common. However, there are many potential contributing factors to injury. While lack of flexibility alone is commonly related to injury, there are clear differences in hamstring flexibility between males and females.', 'To compare the effect of static hamstring length on sagittal plane mechanics between male and female runners.', 'Forty subjects (30.0\u00b16.4 years) participated and were placed in one of 4 groups: flexible males (n=10), inflexible males (n=10), flexible females (n=10), and inflexible females (n=10). All subjects were free of injury at the time of data collection. Three-dimensional kinematics and kinetics were collected while subjects ran over ground across 2 force platforms. Sagittal plane joint angles and moments were calculated at the knee and hip and compared with a 2-way (sex X flexibility) ANOVA (\u03b1=0.05).', 'Males exhibited greater peak knee extension moment than females (M=2.80\u00b10.47, F=2.48\u00b10.52 Nm/kg*m, p=0.05) and inflexible runners exhibited greater peak knee extension moment than flexible runners (In=2.83\u00b10.56, Fl=2.44\u00b10.51 Nm/kg*m, p=0.01). For hip flexion at initial contact, a significant interaction existed (p<0.05). Flexible females (36.7\u00b17.4\u00ba) exhibited more hip flexion than inflexible females (27.9\u00b14.6\u00ba, p<0.01) and flexible males (30.1\u00b19.5\u00ba, p<0.05). No differences existed for knee angle at initial contact, peak knee angle, peak hip angle, or peak hip moment.",
            "output": [
                "Do male and female runners demonstrate different sagittal plane mechanics as a function of static hamstring flexibility?"
            ]
        },
        {
            "id": "task847-e2f97fae93a5469a8aaa87945949594d",
            "input": "The recruitment and commitment of mesenchymal stem cells and their terminal differentiation into adipocytes are the main pathways for increasing adipocyte cell numbers during obesity. Our previous studies have shown that lysyl oxidase (Lox) is upregulated and functions as an essential factor during bone morphogenetic protein 4 (BMP4) -induced C3H10T1/2 cell adipocytic lineage commitment. However, the mechanism of Lox regulation during adipogenic lineage commitment has remained largely unestablished.', 'Samples of adipose tissue from humans with different BMI and C57BL/6 mice with a high-fat diet were used to compare microRNA-27 (miR-27) expression level associated with obesity. Taqman assays were used for miR-27 expression detection and Oil Red O staining for adipogenesis analysis.', \"A negative correlation was identified between Lox expression level and miR-27 expression in both BMP4-treated C3H10T1/2 cells and human subcutaneous adipose tissues. A Lox 3' UTR luciferase reporter assay showed that miR-27 directly targeted Lox. Furthermore, overexpression of miR-27 impaired BMP4-induced upregulation of Lox and adipocytic commitment, which could be rescued by overexpression of mature Lox. Conversely, miR-27 inhibition by specific inhibitors increased Lox expression and adipocytic commitment.",
            "output": [
                "Does miR-27 impair the adipogenic lineage commitment via targeting lysyl oxidase?"
            ]
        },
        {
            "id": "task847-b6bacab78fca4f98b6cba697ddf7b521",
            "input": "Thyroid-stimulating hormone (TSH) levels within populations do not follow Gaussian distribution, and normal limits are derived after mathematical normalization. The clinical relevance of these limits is unknown. The objective of this study was to compare upper and lower TSH limits by four data normalization methods with non-normalized data and assess their clinical relevance.', 'Results of blood samples taken by community physicians and stored in a computerized database were analysed after removing samples from patients with evidence of thyroid illness. TSH values were normalized by the Hoffmann and Tukey methods and each method with natural log transformation. Non-normalized data for TSH in the uppermost and lowermost percentile were also calculated. Clinical relevance was determined by alterations in thyroid hormone levels at, below and above the limits for each method.', 'The maximal reduction from non-normalized data for the upper normal limit (UNL) was by the Hoffman method 43% = 3\u00b71 mIU/l). The maximal increase for the lower normal limit (LNL) was also by the Hoffman method (708% = 0\u00b781 mIU/l). There was very limited difference in average FT3 and FT4 between patients with TSH within, below or above the normal range for all methods.",
            "output": [
                "Do normal limits for serum thyrotropin vary greatly depending on method?"
            ]
        },
        {
            "id": "task847-616b8c0905e44444afc01ec1df96e67e",
            "input": "For slim patients eligible to breast reconstruction, clinical concerns exist on availability of adequate amount of donor tissue to restore breast volume and challenges in donor-site closure, when using the deep inferior epigastric perforator (DIEP) flap. The purpose of the current study is to analyze whether the DIEP flap can provide adequate volume for breast reconstruction in slim patients, without increased complication rates or prolonged hospital stay.', 'All patients receiving a unilateral DIEP breast reconstruction at the center 2007-2010 were included (n\\u2009=\\u2009171). The patients were analyzed in subgroups of delayed and immediate reconstruction and of BMI. Complications were analyzed according to Clavien-Dindo. Flap weight was compared to mastectomy specimen weight among immediate reconstructions (n\\u2009=\\u200991).', 'There was no difference in specimen to flap weight ratio between the different BMI-groups (BMI <25, 25-29.9 and >30: 0.81, 0.87 and 0.96 respectively, P\\u2009=\\u20090.360. Overall complication rate was 43.1% (BMI <25); 43.0% (BMI 25-29.9): and 70.0% (BMI >30) (P\\u2009=\\u20090.018). The results were similar for both the immediate and the delayed reconstructions. Length of hospital stay was similar in the different BMI groups. Delayed donor-site healing was higher in patients with BMI <25; 17.2%, compared to patients with BMI 25-29.9; 11.8%, but lower than for patients with BMI >30; 29.7% (P\\u2009=\\u20090.033).",
            "output": [
                "Is breast reconstruction with the deep inferior epigastric perforator flap a reliable alternative in slim patients?"
            ]
        },
        {
            "id": "task847-11a23dc8cbf144fe8bc943be1f62ec89",
            "input": "In patients with occlusion of the middle cerebral artery (MCA) treated by intravenous thrombolysis (IVT), the distance to thrombus (DT) has been proposed as a predictor of outcome. The purpose of the present study was to investigate how DT relates to dynamic susceptibility contrast perfusion metrics.', 'Retrospective analysis was undertaken of patients who were diagnosed with acute MCA occlusion by magnetic resonance imaging and treated with IVT. Volumes of time-to-maximum (Tmax) perfusion deficits and diffusion-weighted imaging (DWI) lesions, diffusion-perfusion mismatch volumes, and the presence of target mismatch were determined. Correlations between the above stoke measures and DT were then calculated.', 'Fifty-five patients were included. DT showed significant inverse correlations with Tmax greater than 4, 6, 8, and 10 seconds, respectively, and mismatch volumes. Using the DT group median (14 mm) as a separator, significant intergroup differences were observed for Tmax greater than 4, 6, and 8 seconds, respectively, and for mismatch volumes. Grouping DT into quartiles showed significant intergroup differences regarding mismatch volumes and Tmax values greater than 4 and 6 seconds. Binary logistic regression identified DT (odds ratio [OR]\\u2009=\\u2009.89; 95% confidence interval [CI], .81-.99) and DWI lesion volumes (OR = .92; 95% CI, .86-.97) as independent predictors of target mismatch. A low DT predicted target mismatch with an area under the curve of .69.",
            "output": [
                "Does distance to Thrombus in Acute Middle Cerebral Artery Occlusion predict Target Mismatch and Ischemic Penumbra?"
            ]
        },
        {
            "id": "task847-723579d841b345819562e172b57bc26e",
            "input": "Retrospective cohort study.', 'To compare short-term morbidity for primary and revision posterior lumbar fusions.', 'Revision lumbar fusions are unfortunately relatively common. Previous studies have described an increased risk of postoperative complications after revision lumbar fusion; however, these studies have been limited by small sample sizes, poor data quality, and/or narrow outcome measures. There is a need to validate these findings using a high-quality, national cohort of patients to have an accurate assessment of the relative risk of revision posterior lumbar fusions compared with primary lumbar fusion.', 'The prospectively-collected American College of Surgeons National Surgical Quality Improvement Program database was used to identify patients that underwent undergoing primary and revision posterior lumbar fusion from 2005 to 2013. The occurrence of individual and aggregated postoperative complications within 30 days, along with rates of blood transfusion and readmission, were compared between primary and revision procedures using bivariate and multivariate Poisson regression with robust error variance to control for patient and operative characteristics. Operative time and postoperative length of stay were compared between groups using bivariate and multivariate linear regression.', 'Of the 14,873 posterior lumbar fusion procedures that met inclusion criteria, 1287 (8.7%) were revision cases. There were no differences in the rates of 30-day postoperative complications or readmission between primary and revision posterior lumbar fusion using multivariate analysis to control for patient and operative characteristics. Similarly, no significant differences were found for operative time or postoperative length of stay. There was an increased rate of blood transfusion for revision surgery compared with primary surgery (relative risk 1.4, P\\u200a<\\u200a0.001).",
            "output": [
                "Do primary and Revision Posterior Lumbar Fusion Have Similar Short-Term Complication Rates?"
            ]
        },
        {
            "id": "task847-efe76014936a4816943cedb00dd3faaf",
            "input": "Recurrence of colorectal cancer (CRC) may arise due to the persistence of drug-resistant and cancer-initiating cells that survive exposure to chemotherapy. Proteins responsible for this recurrence include the chemokine receptor CXCR4, which is known to enable CRC metastasis, as well as the cancer-initiating cell marker and peptidase CD26, which terminates activity of its chemokine CXCL12.', 'We evaluated the expression and function of CXCR4 and CD26 in colon cancer cell lines and xenografts following treatment with common chemotherapies using radioligand binding, flow cytometry, immunofluorescence, and enzymatic assays.', '5-Fluorouracil, oxaliplatin and SN-38 (the active metabolite of irinotecan), as well as cisplatin, methotrexate and vinblastine, each caused decreases in cell-surface CXCR4 and concomitant increases in CD26 on HT-29, T84, HRT-18, SW480 and SW620 CRC cell lines. Flow cytometry indicated that the decline in CXCR4 was associated with a significant loss of CXCR4+/CD26- cells. Elevations in CD26 were paralleled by increases in both the intrinsic dipeptidyl peptidase activity of CD26 as well as its capacity to bind extracellular adenosine deaminase. Orthotopic HT-29 xenografts treated with standard CRC chemotherapeutics 5-fluorouracil, irinotecan, or oxaliplatin showed dramatic increases in CD26 compared to untreated tumors. Consistent with the loss of CXCR4 and gain in CD26, migratory responses to exogenous CXCL12 were eliminated in cells pretreated with cytotoxic agents, although cells retained basal motility. Analysis of cancer-initiating cell CD44 and CD133 subsets revealed drug-dependent responses of CD26/CD44/CD133 populations, suggesting that the benefits of combining standard chemotherapies 5-fluoruracil and oxaliplatin may be derived from their complementary elimination of cell populations.",
            "output": [
                "Do chemotherapeutic agents attenuate CXCL12-mediated migration of colon cancer cells by selecting for CXCR4-negative cells and increasing peptidase CD26?"
            ]
        },
        {
            "id": "task847-5ca9939c63094a969e35129f1697f4fe",
            "input": "Ficus religiosa L. is one of the most relevant members of the family of Moraceae. It is the most sacred tree of South Asia, and it is used in traditional Ayurvedic and Unani medicine to cure respiratory disorders like cough, wheezing and asthma. Some studies were performed to investigate the anti-asthmatic potential of F. religiosa bark, leaves and fruit extracts but none of them tested their antiviral activity against viruses responsible for the exacerbation of wheezing and asthma.', 'The present study was undertaken to investigate the antiviral activity of F. religiosa L. extracts against respiratory viruses such as human respiratory syncytial virus (RSV) and human rhinovirus (HRV).', 'The antiviral activity of F. religiosa L. was tested in vitro by plaque reduction and virus yield assays and the major mechanism of action was investigated by virus inactivation and time-of-addition assays.', 'F. religiosa L. methanol bark extract was the most active against HRV with an EC50 of 5.52 \u00b5g/mL. This extract likely inhibited late steps of replicative cycle. Water bark extract was the most active against RSV with an EC50 between 2.23 and 4.37 \u00b5g/mL. Partial virus inactivation and interference with virus attachment were both found to contribute to the anti-RSV activity. Replication of both viruses was inhibited in viral yield reduction assays.",
            "output": [
                "Do ficus religiosa L. bark extracts inhibit human rhinovirus and respiratory syncytial virus infection in vitro?"
            ]
        },
        {
            "id": "task847-8c3ffee1b84740fa866caeacd477b8a6",
            "input": "Efforts to improve outcomes from acute kidney injury (AKI) have focussed on timely diagnosis and effective delivery of basic patient care. Electronic alerts (e-alerts) for AKI have attracted interest as a tool to facilitate this. Initial feasibility has already been demonstrated; this review will discuss recent advances in alert methodology, implementation beyond single centres and reported effect on outcomes.', 'On-going descriptions of e-alerts highlight increasing variation in both detection algorithms and alert processes. In England, this is being addressed by national rollout of a standardized detection algorithm; recent data have shown this to have good diagnostic performance. In critical care, fully automated detection systems incorporating both serum creatinine and urine output criteria have been developed. A recent randomized trial of e-alerts has also been reported, in which isolated use of a text message e-alert did not affect either clinician behaviour or patient outcome.",
            "output": [
                "Does recent developments in electronic alert for acute kidney injury?"
            ]
        },
        {
            "id": "task847-87614716aab34b42976c2baa4043a946",
            "input": "Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high-glucose medium as a model of DM.', 'PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)-(\u03baB signaling pathway. The involvement of NF-\u03baB was investigated with a specific NF-\u03baB inhibitor in PDLSCs under hyperglycemic conditions.', 'High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF-\u03baB activation and subsequent interleukin (IL)-6 and IL-8 expression. Treatment with an NF-\u03baB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL-6 expression caused by the high-glucose environment.",
            "output": [
                "Do high Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts?"
            ]
        },
        {
            "id": "task847-e84a875deb0d411d8053efdda2fe8fff",
            "input": "Recently, extract of Ginkgo biloba leaves (GbE) have become widely known phytomedicines and have shown various pharmacological activities, including improvement of blood circulation, protection of oxidative cell damage, prevention of Alzheimer's disease, treatment of cardiovascular disease and diabetes complications. This study was designed to investigate the effects of an ethanolic GbE on renal fibrosis in diabetic nephropathy (DN) and to clarify the possible mechanism by which GbE prevents renal fibrosis.\", 'We investigated the protective effects of GbE on renal fibrosis in STZ-induced diabetic rats. Rats were randomized into six groups termed normal control, diabetes mellitus, low dose of GbE (50\\xa0mg/kg/d), intermediate dose of GbE (100\\xa0mg/kg/d), high dose of GbE (200\\xa0mg/kg/d) and rapamycin (1\\xa0mg/kg/d).', 'After 12 weeks, the rats were sacrificed and then fasting blood glucose (FBG), creatinine (Cr), blood urea nitrogen (BUN), urine protein, relative kidney weight, glycogen and collagen accumulation, and collagen IV and laminin expression were measured by different methods. The amounts of E-cadherin, \u03b1-SMA and snail, as well as the phosphorylation of Akt, mTOR and p70S6K in the renal cortex of rats, were examined by western blotting.', 'Compared with diabetic rats, the levels of Cr, BUN, urine protein, relative kidney weight, accumulation of glycogen and collagen, and expression of collagen IV and laminin in the renal cortex were all decreased in GbE treated rats. In addition, GbE reduced the expression of E-cadherin, \u03b1-SMA, snail and the phosphorylation of Akt, mTOR and p70S6K in diabetic renal cortex.",
            "output": [
                "Does ethanolic Ginkgo biloba leaf extract prevent renal fibrosis through Akt/mTOR signaling in diabetic nephropathy?"
            ]
        },
        {
            "id": "task847-69e2ee2f861b441095303e8a9bb587b9",
            "input": "Cyclin-dependent kinase inhibitor p15(INK4b) is thought to be an important player in regulating astrocytic cell cycle. However, little is known with regard to the expression of p15(INK4b) and its function in hippocampal astrocytes. This study evaluated the expression of p15(INK4b) and its function during different development stages in hippocampal astrocytes.', 'In this study, we cultured hippocampal astrocytes from neonatal adult and aged rats. The expression of p15(INK4b) in neonatal, adult and aged astrocytes was examined. Short interfering RNA (siRNA) was then used to study the functional effects of p15(INK4b) down-regulation during cell cycle regulation.', 'We found the expression of p15(INK4b) in hippocampal astrocytes was detectable on postnatal day 7, was expressed at moderate levels in adult mice (9\\xa0months old) astrocytes and peaked in aged rat (24\\xa0months old) astrocytes. Incubation with siRNA significantly suppressed p15(INK4b) expression at the mRNA and protein levels in astrocytes. Down-regulation of p15(INK4b) increased [(3)H]-thymidine incorporation into DNA and allowed cells to pass the G0/G1-S checkpoint in aged but not in neonatal or adult astrocytes.",
            "output": [
                "Does p15 ( INK4b ) regulate cell cycle signaling in hippocampal astrocytes of aged rats?"
            ]
        },
        {
            "id": "task847-1f3669cf378045249b7daada669a182b",
            "input": "Existing dogma that a female is born with fixed number of eggs was challenged by the detection of stem cells in adult mammalian ovary. Data has accumulated in support of ovarian stem cells (OSCs) proliferation, maintenance in culture, formation of germ cell nests and differentiation into oocytes and primordial follicle assembly using different strategies.', 'Flow cytometry analysis identified >8\\xa0\u03bcm OSCs which are DDX1 positive and are considered equivalent to spermatogonial stem cells (SSCs) in testis. Analysis of both ovarian and testicular smears obtained after enzymatic digestion has led to the identification of an additional stem cell population termed very small embryonic-like stem cells (VSELs). VSELs and OSCs/SSCs differ from each other in their size and OCT-4 expression. VSELs express pluripotent markers including nuclear OCT-4 whereas OSCs/SSCs express cytoplasmic OCT-4 suggesting a differentiated state. VSELs can be studied by flow cytometry as small sized cells which are LIN-/CD45-/Sca-1+. We have reported 0.02\\u2009\u00b1\\u20090.008, 0.03\\u2009\u00b1\\u20090.017 and 0.08\\u2009\u00b1\\u20090.03\\xa0% of total cells as VSELs in normal, chemoablated and after FSH treatment to chemoablated mouse ovary.",
            "output": [
                "Are ovarian stem cells always accompanied by very small embryonic-like stem cells in adult mammalian ovary?"
            ]
        },
        {
            "id": "task847-5b7522f19e644db8ae0dd00ccd035465",
            "input": "Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50-100% mortality, typically from respiratory complications.', 'Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP.', 'Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study.', 'Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics.', 'Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly.', 'Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study.', 'Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health.",
            "output": [
                "Does asfotase Alfa Treatment improve Survival for Perinatal and Infantile Hypophosphatasia?"
            ]
        },
        {
            "id": "task847-d03e290571924656a4add99db89a6895",
            "input": "Inappropriate Sinus Tachycardia (IST), a syndrome characterized by abnormally fast sinus rates and multisystem symptoms, is still poorly understood. Because of the relevance of HCN4 channels to pacemaker activity, we used a candidate-gene approach and screened IST patients for the presence of disease-causing HCN4 mutations.', 'Forty-eight IST patients, four of whom of known familial history, were enrolled in the study. We initially identified in one of the patients with familial history the R524Q mutation in HCN4. Investigation extended to the family members showed that the mutation co-segregated with IST-related symptoms. The R524Q mutation is located in the C-linker, a region known to couple cAMP binding to channel activation. The functional relevance of the mutation was investigated in heterologous expression systems by patch-clamp experiments. We found that mutant HCN4 channels were more sensitive to cAMP than wild-type channels, in agreement with increased sensitivity to basal and stimulated adrenergic input and with a faster than normal pacemaker rate. The properties of variant channels indicate therefore that R524Q is a gain-of-function mutation. Increased channel contribution to activity was confirmed by evidence that when spontaneously beating rat newborn myocytes were transfected with R524Q mutant HCN4 channels, they exhibited a faster rate than when transfected with wild-type HCN4 channels.",
            "output": [
                "Is a gain-of-function mutation in the cardiac pacemaker HCN4 channel increasing cAMP sensitivity associated with familial Inappropriate Sinus Tachycardia?"
            ]
        },
        {
            "id": "task847-fe8033ec59014fb8aaa67eaaf03dab88",
            "input": "The adoption of standardized protocols and specialized multidisciplinary teams for esophagectomy involve changes in routines with the implantation of expensive clinical practices and deviations from ingrained treatment philosophies.', 'To evaluate the prevalence of standardized protocols and specialized multidisciplinary teams in S\u00e3o Paulo state, Brazil.', 'Institutions that routinely perform esophagectomies in S\u00e3o Paulo were contacted and questioned about the work team involved in the procedure and the presence of standardized routines in the preoperatory care.', 'Fifteen centers answered the questionnaire: 10 (67%) public institutions and five (33%) private. There were seven (47%) medical schools, six (40%) with a residency program and two (13%) nonacademic institutions. The mean number of esophagectomies per year was 23. There was a multidisciplinary pre-operative team in nine (60%). There was a multidisciplinary postoperative team in 11 (73%). Early mobilization protocol was adopted in 12 (80%) institutions, early feeding in 13 (87%), routinely epidural in seven (47%), analgesia protocol in seven (47%), hydric restriction in six (40%), early extubation in six (40%), standardized hospitalization time in four (27%) and standardized intensive care time in two (13%).",
            "output": [
                "Are standardized clinical pathways for esophagectomy a reality in Brazil , even with a high prevalence of esophageal cancer and achalasia?"
            ]
        },
        {
            "id": "task847-362c269426384f38a44fddce80f971fc",
            "input": "To investigate the feasibility of inducing adipose-derived stem cells (ADSCs) to nucleus pulposus cells (NPCs).', 'ADSCs were isolated from rabbit while NPCs were isolated from an allogeneic rabbit. NPCs were co-cultured with the 3rd generation ADSCs in co-cultured system. Only NPCs were cultured in single culturing group. Through the collagen type II collagen immunohistochemistry, we observed NPCs and then identify NPC. Proteoglycan messenger RNA (mRNA) and collagen type II mRNA level were measured by real-time polymerase chain reaction.', 'In two group cells, collagen type II collagen were detected by immunohistochemistry. The amount of proteoglycan mRNA and collagen type II mRNA was both significantly higher in co-cultured group than in single cultured group.",
            "output": [
                "Do rabbit nucleus pulposus cells facilitate differentiation of adipose-derived stem cells into nucleus pulposus-like cells?"
            ]
        },
        {
            "id": "task847-bc729e44c59c4188865a5b22d6deb44d",
            "input": "Human Nucleic Acid Binding Protein 1 and 2 (hNABP1 and 2; also known as hSSB2 and 1, respectively) are two newly identified single-stranded (ss) DNA binding proteins (SSB). Both NABP1 and NABP2 have a conserved oligonucleotide/oligosaccharide-binding (OB)-fold domain and a divergent carboxy-terminal domain, the functional importance of which is unknown.', 'Recombinant hNABP1/2 proteins were purified using affinity and size exclusion chromatography and their identities confirmed by mass spectrometry. Oligomerization state was checked by sucrose gradient centrifugation. Secondary structure was determined by circular dichroism spectroscopy. Nucleic acid binding ability was examined by EMSA and ITC.', 'Both hNABP1 and hNABP2 exist as monomers in solution; however, hNABP2 exhibits anomalous behavior. CD spectroscopy revealed that the C-terminus of hNABP2 is highly disordered. Deletion of the C-terminal tail diminishes the DNA binding ability and protein stability of hNABP2. Although both hNABP1 and hNABP2 prefer to bind ssDNA than double-stranded (ds) DNA, hNABP1 has a higher affinity for ssDNA than hNABP2. Unlike hNABP2, hNABP1 protein binds and multimerizes on ssDNA with the C-terminal tail responsible for its multimerization. Both hNABP1 and hNABP2 are able to bind single-stranded RNA, with hNABP2 having a higher affinity than hNABP1.",
            "output": [
                "Are c-termini essential and distinct for nucleic acid binding of human NABP1 and NABP2?"
            ]
        },
        {
            "id": "task847-c5c7da03132147638a4a8343d4546dc6",
            "input": "Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in MYO5B or syntaxin 3 (STX3) affecting apical membrane trafficking. Morphologically, MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis, we examined the location of essential apical polarity determinants in five MVID patients.', 'We found that the polarity determinants Cdc42, Par6B, PKC\u03b6/\u03b9 and the structural proteins ezrin and phospho-ezrin were lost from the apical membrane and accumulated either in the cytoplasm or on the basal side of enterocytes in patients, which suggests an inversion of cell polarity. Moreover, microvilli-like structures were observed at the basal side as per electron microscopy analysis. We next performed Myo5B depletion in three dimensional grown human Caco2 cells forming cysts and found a direct link between the loss of Myo5B and the mislocalisation of the same apical proteins; furthermore, we observed that a majority of cysts displayed an inverted polarity phenotype as seen in some patients. Finally, we found that this loss of polarity was specific for MVID: tissue samples of patients with Myo5B-independent absorption disorders showed normal polarity but we identified Cdc42 as a potentially essential biomarker for trichohepatoenteric syndrome.",
            "output": [
                "Is the localisation of the apical Par/Cdc42 polarity module specifically affected in microvillus inclusion disease?"
            ]
        },
        {
            "id": "task847-f6aeb632b69947188b4f48559f4c4eea",
            "input": "the nutritional content and energy density of foods is related to greater control of appetite, satiety and reducing food intake.', 'the randomized crossover study included 20 healthy women, aged 20 and 30 years with a BMI of 20 to 24.9 kg/m2 and who completed that included 3 day trial comparing 8 hours 130 kcal snacks consumed afternoon: yoghurt with added whey protein (PSL), biscuits and chocolate. Participants consumed a standardized menu; snack was consumed 3 hours after lunch. Perceived hunger and fullness were evaluated during the afternoon until dinner voluntary intake ad libitum. They repeat the same snack 3 times.', 'consumption of yogurt with PSL led to a further reduction of appetite in the afternoon in front of the snack of chocolate and biscuits (p < 0.001). No differences of appetite in the afternoon between chocolate vs cookies but significant difference between yogurt with PSL and other treatments (p < 0.001) were detected. At snack, yogurt there was a significant reduction in caloric intake compared to other snacks (p < 0.001) and a later request for dinner with about 45 minutes apart.",
            "output": [
                "Does [ SNACK HIGH WHEY PROTEIN improve THE LEVEL OF SATIETY AND REDUCES APPETITE HEALTHY WOMEN ]?"
            ]
        },
        {
            "id": "task847-971e1002b67a4676a15615ada7037d79",
            "input": "Acidic diets are advocated as main risk factor for tooth erosion, which could be prevented, or at least controlled, if patients were early advised. It is important to identify, hence, if possible dietary constituents regionally consumed on large scale, such as tucupi, a low-pH yellowish-green color and strong flavor delicacy made from the juice of a bitter cassava, may explain its occurrence in specific patient groups. This cross-over in situ/ex vivo study evaluated tucupi's ability to promote erosion of bovine enamel by assessing its percentage of surface microhardness change (%SMHC), taking a cola-based soft drink and human saliva as positive and negative controls.\", \"For three 7-days spaced out legs of 7 days each, nine volunteers wore palatal devices with three bovine enamel blocks, which were challenged with one of the following solutions: TUC-tucupi (n=27); COL-cola-based soft drink (n=27); SAL-saliva (n=27). Erosive challenges were performed extra-orally (4\u00d7/day) by dropping TUC or COL at room temperature on specimens. After 5min, palatal devices were replaced into the mouth. SAL permanently acted as the negative control while volunteers solely wore the device. One-way ANOVA followed by Tukey's post-hoc tests (\u03b1=0.05) were applied.\", 'TUC promoted an enamel %SMHC (-21.56\u00b110.08(a)) similar than that promoted by COL (-18.19\u00b112.99(a); p=0.275), which were both significantly higher than that promoted by SAL (-1.86\u00b113.65(b); p<0.0001).",
            "output": [
                "Is amazonian delicacy tucupi as erosive as a cola-based soft drink?"
            ]
        },
        {
            "id": "task847-efebb005050d481f819d61ccc8991121",
            "input": "To examine whether differences emerged when the Chinese version of the Movement-Specific Reinvestment Scale (MSRS-C) was administered to community-dwelling older adults with instructions to respond in the context of \"general\" movements, walking, using chopsticks or dressing. Furthermore, the difference between the six-point Likert scale and four-point Likert scale response formats of the MSRS-C was investigated.', 'The study was implemented in the community of Hong Kong with 52 older adults (mean age 77.4 years). Telephone interviews were carried out on two occasions for each participant. Participants provided a verbal response to each of 10 questions from the MSRS-C with different response formats (i.e., six-point or four-point Likert Scales) and different instructions in the response context (i.e. general, walking, using chopsticks, dressing). The sequence of response format and context was randomized for each participant.', 'Older fallers scored significantly higher on the MSRS-C (general) with six-point or four-point response formats than non-fallers. The MSRS-C (general) and MSRS-C (walking) were not statistically different, and showed good discriminative power for previous older fall status (older fallers or older non-fallers). However, MSRS-C (chopsticks) and MSRS-C (dressing) failed to differentiate older fallers from older non-fallers.",
            "output": [
                "Do instructions influence response to the Chinese version of the Movement-Specific Reinvestment Scale in community-dwelling older adults?"
            ]
        },
        {
            "id": "task847-e2ec34c023ab41a680c1e2f7dde3d939",
            "input": "Schatzki rings are found in the distal esophagus, are associated with hiatal hernias, and present with intermittent dysphagia to solid foods. They can be identified by radiology (GI series or barium swallow studies) or endoscopy. Rings are not always visualized during endoscopy in patients in whom they are suspected clinically. The Bolster technique involves application of epigastric abdominal pressure, which offers the potential to reveal a Schatzki ring that is otherwise obscured within a reduced hiatal hernia. The aim of this study was to determine whether the Bolster technique improves endoscopic detection of Schatzki rings.', 'We reviewed 30 symptomatic patients with a history of a Schatzki ring in a tertiary care center. The Bolster technique was applied to patients in whom the ring was not visible during standard endoscopy. The main outcome measurement was identification of the Schatzki ring after the Bolster technique.', 'A Schatzki ring was visible during standard endoscopy in 26 of the 30 patients. In the remaining 4, the ring was visible only after the application of the Bolster technique.",
            "output": [
                "Does abdominal compression during endoscopy ( the Bolster technique ) demonstrate hidden Schatzki rings ( with videos )?"
            ]
        },
        {
            "id": "task847-9a86e0ccbb1e43acaae966829463f2d4",
            "input": "Pemphigus vulgaris (PV) is an autoimmune blistering disease mediated by IgG autoantibodies targeting desmogleins (Dsgs). The anti-CD20 monoclonal antibody rituximab is increasingly used in corticosteroid-resistant PV patients. In a subset of rituximab-treated patients in remission, high ELISA index values have been reported; however, their significance remains so far unclear.', 'To address the discrepancy between anti-Dsg3 serum antibody titers and disease severity.', '6 rituximab-treated PV patients were prospectively followed-up for two years and anti-Dsg3 autoantibodies levels and pathogenic activity were measured.', 'All patients achieved complete remission without any serious side effects. Both anti-Dsg3 autoantibodies (p = 0.031) and their pathogenic activity (p = 0.003) were significantly related to disease severity. However, in selected patients, the dissociation index was a more sensitive indicator for PV clinical activity than the ELISA index.",
            "output": [
                "Does the pathogenic activity of anti-desmoglein autoantibodies parallel disease severity in rituximab-treated patients with pemphigus vulgaris?"
            ]
        },
        {
            "id": "task847-7af39061779d4f498be74bed49177e48",
            "input": "To examine whether the elevated preoperative plasma D-dimer levels show correlation with chemoresistance and poor prognosis in serous ovarian cancer patients.', 'Preoperative plasma D-dimer levels were measured in 125 patients with primary serous ovarian cancer (SOC).The correlations of plasma D-dimer levels with clinicopathological features, chemotherapeutic response, and survival outcome were further analyzed. Kaplan-Meier estimates were used to compute the survival functions and were compared using log-rank tests. Cox proportional-hazard regression analysis was used to evaluate the effects of D-dimer on progression-free survival (PFS) and overall survival (OS), controlling for potential confounding factors.', 'The median follow-up period was 49 (range 5-85) months. Elevated plasma D-dimer levels were positively associated with advanced FIGO stage (P = 0.010), residual tumor size (P = 0.017), the presence of malignant ascites (P = 0.028), increased serum CA125 level (P = 0.014), and neo-adjuvant chemotherapy (P = 0.008). The patients with elevated plasma D-dimer levels had significantly higher chemoresistance rates (56.41 %) compared to the normal plasma D-dimer levels (20.93 %). Additionally, it was found by the univariate analysis that elevated plasma D-dimer levels were closely related with a low 5-year PFS rate (28.21 vs 52.33 %, P = 0.002) and a poor 5-year OS (30.77 vs 63.95 %, P < 0.001). However, after adjustment for other factors, high plasma D-dimer levels were only closely correlated with a poor 5-year OS (HR 1.901, 95 % CI 1.021-3.540; P = 0.043).",
            "output": [
                "Is elevated preoperative plasma D-dimer level a useful predictor of chemoresistance and poor disease outcome for serous ovarian cancer patients?"
            ]
        },
        {
            "id": "task847-08a4a9a3a17c4cbf91d9f2bc0b7584f4",
            "input": "Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC).', 'Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS).', 'Of 559 patients, 104 (18.6\\xa0%) who tested positive for H. pylori were younger (62.1 vs 65.1\\xa0years; p\\xa0=\\xa00.041), had a higher frequency of distal tumors (82.7 vs 71.9\\xa0%; p\\xa0=\\xa00.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9\\xa0%; p\\xa0=\\xa00.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2\\xa0months; p\\xa0=\\xa00.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95\\xa0% CI 0.30-0.99; p\\xa0=\\xa00.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7\\xa0months; p\\xa0=\\xa00.018), a trend of longer RFS (31.4 vs 21.6\\xa0months; p\\xa0=\\xa00.232), and longer DSS (44.8 vs 27.2\\xa0months; p\\xa0=\\xa00.034).",
            "output": [
                "Is preoperative Helicobacter pylori Infection Associated with Increased Survival After Resection of Gastric Adenocarcinoma?"
            ]
        },
        {
            "id": "task847-9f601c03e19a4dd7b4bf9020ce81ac79",
            "input": "This study examined the relationship between plasma cholesterol and circulating triiodothyronine and oestradiol in 561 adolescent girls aged 11-17 with eating disorders.', 'Plasma total cholesterol, high-density lipoprotein cholesterol, serum triodothyronine and oestradiol were measured at assessment, and historical weight data were obtained from growth charts provided by the school health services. Cholesterol levels were related to weight change, menstrual status and serum hormones.', 'Plasma total cholesterol levels of >5.0 mmol/L were found in 38% of the 77 girls who were premenarcheal, 32% of the 199 with secondary amenorrhoea and 17% of those who were still menstruating. These cholesterol levels were inversely related to serum oestradiol and triiodothyronine concentrations, but not weight change, in amenorrhoic girls and were positively related to body mass index and inversely related to weight loss and serum triiodothyronine in girls who were still menstruating.",
            "output": [
                "Is plasma cholesterol related to menstrual status in adolescent girls with eating disorders and weight loss?"
            ]
        },
        {
            "id": "task847-8b5c967f5a45494f9bd4947324ca98fe",
            "input": "Evodiamine is one of active alkaloids isolated from the traditional Chinese medicine Evodia rutaecarpa Bentham and has various pharmacological properties. In this study, we investigated its effects on the migration, invasion, and associated mechanism in human nasopharyngeal carcinoma (NPC) cells.', 'Cell viability was determined by MTT assay after evodiamine treatment. Wound-healing assay and Boyden transwell system were used to evaluate the inhibitory effects of evodiamine on cell migration and invasion. MMP-2/9 activity was determined using commercial detection kits. The levels of associated proteins involved in the regulation of cell migration and invasion were analyzed by Western blotting.', 'Evodiamine effectively inhibited the migration and invasion of HONE1 and CNE1 cells, and hardly affected cell proliferation, but significantly suppressed cell adhesion activity in vitro. Additionally, evodiamine treatment significantly decreased mRNA and protein levels of MMP-2 and its activity in the NPC cells, but had little effects on MMP-9 mRNA and protein levels and its activity. Further investigation revealed that evodiamine inhibited the translocation of NF-\u03baB p65, which involves the regulation of MMP-2 expression in cancer invasion. Additionally, evodiamine treatment did not significantly affect the protein levels of JNK, p38, Akt, and their phosphorylated forms and ERK1/2, but strongly attenuated ERK1/2 phosphorylation level, which at least partly accounts for the signal pathway of evodiamine-inhibited migration and invasion of NPC cells.",
            "output": [
                "Does evodiamine inhibit the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression?"
            ]
        },
        {
            "id": "task847-36791e6009ba41a4b4a51000e5220332",
            "input": "To evaluate the association between SLC22A1 expression and the outcomes of hepatocellular carcinoma (HCC) patients.', \"A tissue microarray of 303 HCC and matched adjacent noncancerous liver tissues (ANLTs) were constructed. The expression of SLC22A1 was tested by immunohistochemistry (IHC) and scored by two pathologists according to a 12-score scale (a score>6 was defined as high expression, and a score\u22646 as low expression). The correlation of SLC22A1 expression with the clinicopathological features and the patients' outcome was analyzed.\", 'All the ANLTs had a IHC score of 12, as compared to only 29 (9.6%) of the HCC tissues. The patients were divided into 2 groups based on the IHC scores: 59% (180/303) in low expression group and 41% (123/303) in high expression group. The disease-free survival (DFS) rates and overall survival (OS) rates were significantly lower in low SLC22A1 expression group than in the high expression group. The 1-, 3-, and 5-year DFS rates were 43%, 31% and 27% in the low expression group, and were 58%, 47% and 43% in the high expression group, respectively. The 1-, 3-, and 5-year OS rates were 66%, 38% and 32% in low expression group, and were 80%, 57% and 50% in the high expression group, respectively. A low expression of SLC22A1 was positively correlated with the tumor diameter, BCLC stage, tumor differentiation, and AFP levels (P<0.05), and was an independent predictor of poor overall survival (HR=1.454; 95% CI, 1.050-2.013).",
            "output": [
                "Is [ Low expression of SLC22A1 associated with a poor prognosis of hepatocellular carcinoma : analysis of 303 patients ]?"
            ]
        },
        {
            "id": "task847-6e8119b4cbfe49c0bd5a2f8019f134f9",
            "input": "Reports on outcome after posterior cruciate ligament (PCL) reconstruction often contain both isolated PCL and combined knee ligament injuries. This makes it difficult to conclude on the outcome after reconstruction of isolated PCL injuries.', 'To investigate the outcome after PCL reconstruction in patients with an isolated PCL injury and to compare this with the outcome of patients treated with reconstruction after isolated anterior cruciate ligament (ACL) injuries.', 'Cohort study; Level of evidence, 3.', 'Seventy-one patients with an isolated PCL injury that was reconstructed surgically and who had registered in the Norwegian Knee Ligament Registry between 2004 and 2010 were included in this study. Patients with isolated ACL reconstructions (n = 9661) who had registered in the same period were included for comparison. Knee Injury and Osteoarthritis Outcome Score (KOOS) was used as the patient-reported outcome measure. Preoperative and 2-year postoperative KOOS scores were compared. Changes in KOOS score reported by the PCL patients were compared with changes reported by the ACL patients.', 'At the 2-year postoperative follow-up of the PCL-reconstructed patients, the patient-reported outcome was improved, measured by KOOS as follows: pain, 15.1 (95% CI, 8.5-21.8; P < .001); symptoms, 0.9 (95% CI, -6.6 to 8.3; P = .82); activities of daily living, 13.2 (95% CI, 6.6-13.9; P < .001); sports, 20.7 (95% CI, 11.8-29.4; P < .001); and quality of life, 26.6 (95% CI, 18.9-34.2; P < .001). According to the KOOS, the incremental improvements were similar for PCL and ACL patients. Time from injury to surgery was longer for the PCL patients compared with ACL patients (median, 21.5 vs 8.0 months; P < .001).",
            "output": [
                "Do patients With Isolated PCL Injuries Improve From Surgery as Much as Patients With ACL Injuries After 2 Years?"
            ]
        },
        {
            "id": "task847-5cac158bf647406294101ad7bb039b44",
            "input": "To explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms.', 'We measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot.', 'The viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 \u00b5mol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 \u00b5mol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.",
            "output": [
                "Does [ Indirubin inhibit the proliferation of prostate cancer PC-3 cells ]?"
            ]
        },
        {
            "id": "task847-b032001d3b4a40039741e53376a69fc4",
            "input": "To investigate whether intracytoplasmic sperm injection (ICSI) can improve the clinical outcomes of the male patients with 100% teratozoospermia.', 'We retrospectively analyzed the clinical data of 152 couples undergoing in vitro fertilization-embryo transfer (IVF-ET), including 75 cycles of IVF and 77 cycles of ICSI. We compared the rates of normal fertilization, high-quality embryos, transferrable embryos, implantation, clinical pregnancy, and abortion between the two groups.', 'In the 100% teratozoospermia patients the number of transferrable embryos was significantly lower in the IVF than in the ICSI group (78.91% vs 84.92%, P < 0.05), while the rates of normal fertilization and implantation were higher in the former than in the latter (60.26% vs 57.87% and 48.00% vs 39.55%, both P > 0.05). There were no statistically significant differences between the two groups in the female age, Gn days, Gn dose, BMI, infertility duration, endometrial thickness, and basal serum FSH and E2.",
            "output": [
                "Does [ Intracytoplasmic sperm injection improve the clinical outcomes of the males with 100 % teratozoospermia ]?"
            ]
        },
        {
            "id": "task847-2fa4cd7e215d4970ad2ef2723f52416c",
            "input": "On the basis of our previous work with triheptanoin, which provides key substrates to the Krebs cycle in the brain, we wished to assess its therapeutic effect in patients with glucose transporter type 1 deficiency syndrome (GLUT1-DS) who objected to or did not tolerate ketogenic diets.', 'We performed an open-label pilot study with three phases of 2 months each (baseline, treatment and withdrawal) in eight patients with GLUT1-DS (7-47 years old) with non-epileptic paroxysmal manifestations. We used a comprehensive patient diary to record motor and non-motor paroxysmal events. Functional (31)P-NMR spectroscopy was performed to quantify phosphocreatine (PCr) and inorganic phosphate (Pi) within the occipital cortex during (activation) and after (recovery) a visual stimulus.', 'Patients with GLUT1-DS experienced a mean of 30.8 (\u00b1 27.7) paroxysmal manifestations (52% motor events) at baseline that dropped to 2.8 (\u00b1 2.9, 76% motor events) during the treatment phase (p = 0.028). After withdrawal, paroxysmal manifestations recurred with a mean of 24.2 (\u00b1 21.9, 52% motor events; p = 0.043). Furthermore, brain energy metabolism normalised with triheptanoin, that is, increased Pi/PCr ratio during brain activation compared to the recovery phase (p = 0.021), and deteriorated when triheptanoin was withdrawn.",
            "output": [
                "Does triheptanoin dramatically reduce paroxysmal motor disorder in patients with GLUT1 deficiency?"
            ]
        },
        {
            "id": "task847-002fe6e795514689910a6e8c77fefd35",
            "input": "Hepatic myofibroblasts are relevant for pathogenesis of S. mansoni infection. In normal liver, these perisinusoidal cells are quiescent, express the lipocyte phenotype, and are located in the Disse's space, being the major site of vitamin A storage. When activated, they convert to myofibroblasts and contribute to granulomatous and diffuse liver fibrosis. In the present work, we observed that myofibroblasts obtained from granulomatous periovular inflammatory reactions in schistosome-infected mice (GR-MF) produce in vitro immunomodulatory cytokines for eosinophil activation: IL-5 and eotaxin.\", 'The secretory activity of GR-MF was detected after TGF-\u03b2 and IL-13 stimulation using 2D and 3D cell culture systems. In a mixed co-culture system using GR-MF with hematopoietic bone marrow cells from infected mice, we observed eosinophil survival that was dependent upon IL-5 and eotaxin, since antibodies against this cytokines decreased eosinophil population, as measured by eosinophil peroxidase activity.",
            "output": [
                "Are hepatic myofibroblasts derived from Schistosoma mansoni-infected mice a source of IL-5 and eotaxin : controls of eosinophil populations in vitro?"
            ]
        },
        {
            "id": "task847-97927cd828d74e35a04d0c2e7e8c75fd",
            "input": "To establish a single-tube single-run multiplex PCR technique that can detect single or mixed samples with four species of Plasmodium.', 'Folding primers were designed based on the fast nested PCR. The reaction component concentrations were optimized and the primers were selected based on the annealing temperature. The established single-tube single-run folding-primer multiplex PCR (FP-PCR) was tested for its sensitivity and specificity to detect single-species and mixed samples with P. vivax, P. falciparum, P. ovale (including P. ovale wallikeri) and/or P. malariae.', 'In all the seven experimental repeats, FP-PCR successfully detected single-species infection for all the four species, with the detection limit reaching or close to 1 parasite/\u00b5l blood. For mixed infections with 2-4 species at different densities with the highest being 100 times of the lowest, FP-PCR identified all the species in each combination in 57 out of 84 tests. Further, in 10 dried blood samples on filter paper from healthy subjects, no FP-PCR amplification was found, except weak formation of dimers.",
            "output": [
                "Does [ Single-tube Single-run Multiplex PCR detect Mixed Samples with Four Species of Plasmodium ]?"
            ]
        },
        {
            "id": "task847-96231504bf04423b87851adbd1a8d4f5",
            "input": "To determine the impact of two apparent diffusion coefficient (ADC) measurement techniques on diffusion-weighted magnetic resonance images (DW MRI) on the assessment of rectal cancer response to neoadjuvant chemoradiotherapy (CRT).', 'ADC values were measured prospectively with two different techniques - the first, which measures ADCs in the most cellular tumor parts, and the second, which measures the entire tumor area, in 58 patients with locally advanced rectal cancer on pre-CRT and post-CRT image sets. Areas under the receiver operating characteristic curves (AUCs) and parameters of diagnostic accuracy were calculated for pre- and post-CRT ADC values and numeric and percent ADC change for each technique to determine their performance in tumor response evaluation using histopathological tumor-regression grade as the reference standard.', 'The second technique yielded higher AUCs (0.935 vs 0.704, P<.001), percent-change (0.828 vs 0.636, P<0.001), and numeric-change (0.866 vs 0.653, P<0.001) than the first technique for post-CRT ADC. Accuracies for post-CRT ADC assessment were 62% for the first and 88% for the second technique (cut-off values: 0.98 and 1.29\u00d710(-3) mm2/s, respectively) and for ADC change assessment, both numeric and percent, 59% and 74%, respectively (cut-off values: increase of 0.18 and 0.28\u00d710(-3) mm(2)/s; increase of 24% and 37%, respectively).",
            "output": [
                "Does apparent diffusion coefficient measurement covering complete tumor area better predict rectal cancer response to neoadjuvant chemoradiotherapy?"
            ]
        },
        {
            "id": "task847-b4b2e455f4af41b6a1c6fbd36ae44f4b",
            "input": "To assess the effects of protein C activator (PCA) from Agkistrodon halys snake venom on cardiac fibrosis in streptozotocin (STZ) induced diabetic rat model, and investigate the mechanisms of its action.', 'PCA was identified by one-dimensional reversed phase liquid chromatography - mass spectrometry/mass spectrometry. Male Sprague-Dawley rats (120-140 g) were randomly assigned to negative control (NC) and diabetic group. Diabetes was induced by STZ in high-fat diet fed rats. Diabetic group was subdivided into three groups: diabetic group (DM), diabetic group treated with PCA (0.5, 2, and 8 mg/kg), and diabetic group treated with metformin (5 mg/kg, positive control). NC and DM groups received the same volume of distilled water. Left ventricular mass index (LVWI) and collagen volume fraction were measured by hematoxylin and eosin and Masson staining. Transforming growth factor beta-1 (TGF-\u03b21) and interleukin 1 beta (IL-1\u03b2) levels were determined by enzyme-linked immunosorbent assay.', 'The diabetic rat model was successfully established by STZ induction and high-fat diet. Glucose level, LVWI, TGF-\u03b21 and IL-1\u03b2 level, and collagen volume fraction were significantly reduced in diabetic rats treated by PCA in a dose-dependent manner (P<0.050), especially in the high dose (8 mg/kg) group (P<0.010), compared to diabetes group. The high dose PCA had the same effect as metformin positive control in reducing the level of fasting blood glucose. PCA decreased the expression of MMP-2 and reduced that of TIMP-2.",
            "output": [
                "Does a new Agkistrodon halys venom-purified protein C activator prevent myocardial fibrosis in diabetic rats?"
            ]
        },
        {
            "id": "task847-edc4adb51e334602be38804c456e7ac5",
            "input": "Primary: to evaluate predictivity of liver stiffness (LS), spleen stiffness (SS), and their ratio assessed by real-time 2D shear wave elastography (RT-2D-SWE) for adverse outcomes (hepatic decompensation, hepatocellular carcinoma or death; \"event\") in compensated liver cirrhosis (LC) patients. Secondary: to evaluate ability of these measures to discriminate between cirrhotic patients with/without esophageal varices (EV).', 'Predictivity of LS, SS, and LS/SS was assessed in a retrospectively analyzed cohort of compensated LC patients (follow-up cohort) and through comparison with incident patients with decompensated cirrhosis (DC) (cross-sectional cohort). Both cohorts were used to evaluate diagnostic properties regarding EV.', 'In the follow-up cohort (n=44) 18 patients (40.9%) experienced an \"event\" over a median period of 28 months. LS\u226521.5 kPa at baseline was independently associated with 3.4-fold (95% confidence interval [CI] 1.16-10.4, P=0.026) higher risk of event. Association between SS and outcomes was weaker (P=0.056), while there was no association between LS/SS ratio and outcomes. Patients with DC (n=43) had higher LS (35.3 vs 18.3 kPa, adjusted difference 65%, 95% CI 43%-90%; P<0.001) than compensated patients at baseline. Adjusted odds of EV increased by 13% (95% CI 7.0%-20.0%; Plt;0.001) with 1 kPa increase in LS. At cut-offs of 19.7 and 30.3 kPa, LS and SS had 90% and 86.6% negative predictive value, respectively, to exclude EV in compensated patients.",
            "output": [
                "Is real-time two-dimensional shear wave ultrasound elastography of the liver a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis?"
            ]
        },
        {
            "id": "task847-456eb6c00d8e4839be41b39f7838a25c",
            "input": "Pigs are frequently used as animal models in experimental medicine. To identify processes of vascular development or regression, vascular elements must be recognised and quantified in a three-dimensional (3D) arrangement. Vascular corrosion casts enable the creation of 3D replicas of vascular trees. The aim of our study was to identify suitable casting media and optimise the protocol for porcine liver vascular corrosion casting.', 'Mercox II\u00ae (Ladd Research, Williston, Vermont, USA) and Biodur E20\u00ae Plus (Biodur Products, Heidelberg, Germany) were tested in 4 porcine livers. The resins (volume approximately 700 mL) were injected via the portal vein. Corrosion casts were examined by macro-computed tomography, micro-computed tomography and scanning electron microscopy.', 'For hepatectomies, the operating protocol was optimised to avoid gas or blood clot embolisation. We present a protocol for porcine liver vascular bed casting based on corrosion specimens prepared using Biodur E20\u00ae epoxy resin.",
            "output": [
                "Does porcine liver vascular bed in Biodur E20 corrosion cast?"
            ]
        },
        {
            "id": "task847-4b27c3b86abf49cdbb2695bea771f82c",
            "input": "Obstetric cholestasis is a cholestatic disease usually commencing in the third trimester of pregnancy and characterized by pruritus, elevation of liver enzymes, and increase in bile acids. The objective of this study was to compare the first trimester serum indicators of obstetric cholestasis with normal pregnancies.', 'Thirty-five patients diagnosed with obstetric cholestasis in a three-year period with first trimester biochemical assessment available were included in the study. Seventy patients with concordant pregnancy weeks, matched-age normal pregnancies were included as the control group. Pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) levels were analyzed.', 'No difference was observed between the two groups in terms of age and week of pregnancy. While the mean PAPP-A level was 0.76 \u00b1 0.31 multiples of the medians (MoM) in the obstetric cholestasis group, it was determined to be 1.5 \u00b1 0.84 in the control group (p = 0.0001). Among the two groups, the hCG levels were found to be higher in the obstetric cholestasis group (1.2 \u00b1 0.79 MoM vs. 0.98 \u00b1 0.53, p = 0.041).",
            "output": [
                "Are pregnancy-associated plasma protein a levels decreased in obstetric cholestasis?"
            ]
        },
        {
            "id": "task847-e789a63a581a4f07ac75f8c22655c8e7",
            "input": "Although clinical investigations indicate that the limit of reversibility of rotator cuff muscles fibers type I and II atrophy is grade 2 of fatty degeneration (FD) according to the Goutallier computed tomography classification, little is known about the morphometric verification of these findings.', 'The supraspinatus tendon was detached from the greater tubercle and the infraspinatus and subscapularis in 12 rabbits, and a 12-week observation period followed. This proved to be sufficient for development of grade >2 FD of the supraspinatus tendon. The tendon was then reinserted. The animals were euthanized 24 weeks after tendon reconstruction. The sections of middle part of supraspinatus were stained for adenosine triphosphatase reaction, and morphometric measurements were taken of type I and II muscle fiber diameters. The contralateral shoulders served as controls.', 'The macroscopic inspection of the supraspinatus tendons revealed complete healing in all cases. No statistically significant differences were found between controls and operated-on shoulders for type I (P = .13) and type II (P = .55) muscle fibers.",
            "output": [
                "Is atrophy of type I and II muscle fibers reversible in the case of grade > 2 fatty degeneration of the supraspinatus muscle : an experimental study in rabbits?"
            ]
        },
        {
            "id": "task847-3d1d3e3c47da4a95a9e0c6b23aa9973c",
            "input": "Pax6, a highly conserved multifunctional transcription factor, has been critical for neurogenesis and neuronal plasticity. It is presumed that if level of Pax6 approaches either low or null, critical genes responsible for maintaining functional status of neurons or glia would be modulated.', 'Therefore, it has been intended to explore possibility of either direct or indirect influence of Pax6 in neurodegeneration.', 'The cell lines having origin of murine embryonic fibroblast (Pax6-non expressing, NIH3T3-cell line), murine neuroblastoma (Pax6-expressing brain-derived, Neuro-2a-cell line), and human glioblastoma-astrocytoma (U87MG) were cultured and maintained in a CO2 incubator at 37\u00b0C and 5% CO2 in DMEM containing 10% fetal bovine serum. The knockdown of endogenous Pax6 in Neuro-2a cells was achieved through siRNA based gene knock-down approach. The efficiency and validation of knock-down was done by real time PCR. The knock-down of Pax6 was successfully achieved.', 'The levels of expression of transcripts of some of the proposed putative markers of neurodegeneration like Pax6, S100\u03b2, GFAP, BDNF, NGN2, p73\u03b1, p73\u03b4, LDH, SOD, and Catalase were analyzed in Pax6 knockdown condition for analysis of role of Pax6 in neurodegeneration. Since the Pax6 has been proposed to bind to promoter sequences of catalase, and catalase suppresses TGF\u03b2, relative lower levels of catalase in Neuro-2a and U-87MG as compared to NIH-3T3 indicates a possible progressive dominant negative impact of Pax6. However, presence of SOD and LDH indicates alternative protective mechanism.",
            "output": [
                "Does pax6 influence expression patterns of genes involved in neuro- degeneration?"
            ]
        },
        {
            "id": "task847-11125e1abc35432585d4271030bbe4c9",
            "input": "With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences.', 'AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells \u22651 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined.', 'AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n\\u2009=\\u200917).",
            "output": [
                "Is androgen receptor status highly conserved during tumor progression of breast cancer?"
            ]
        },
        {
            "id": "task847-7060df5011b04a3fbe0b109411470adc",
            "input": "Cardiac rehabilitation (CR) is recommended after coronary artery bypass graft surgery; however, the consequences of longer wait times to start CR have not been elucidated.', \"Cardiopulmonary, demographic, and anthropometric assessments were conducted before and after 6 months of CR in consecutively enrolled patients from January 1995 to October 2012. Wait times were ascertained from referral forms and charts. Neighborhood characteristics were ascertained using census data and cross-referencing with patients' home geographic location. Among 6497 post- coronary artery bypass graft participants, mean and median total wait time (time from surgery to first exercise session) was 101.1\u00b147.9 and 80 days, respectively. In multiple linear regression, correlates of longer total wait time and the 2 wait-time phases, time from surgery to CR referral and time from CR referral to first exercise session, were determined. Factors influencing longer wait times included female sex, greater age, being employed, less social support, longer drive time to CR, lower neighborhood socioeconomic status, higher systolic blood pressure, abdominal obesity, and a complex medical history. After adjusting for correlates of delayed entry, longer wait time for each of the total and 2 wait-time phases was significantly associated with less improvement in cardiopulmonary fitness (VO2peak; \u03b2=-0.165, P<0.001), body fat percentage (\u03b2=0.032, P<0.02), resting heart rate (\u03b2=0.066, P<0.001), and poorer attendance to CR classes (\u03b2=-0.081, P<0.001) and completion rate (\u03b2=2.741, P<0.001).",
            "output": [
                "Do delays in Referral and Enrolment Are Associated With Mitigated Benefits of Cardiac Rehabilitation After Coronary Artery Bypass Surgery?"
            ]
        },
        {
            "id": "task847-5d9919ec18734424ae39afa2e19c9225",
            "input": "Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory markers used as prognostic factors in various diseases. The aims of this study were to compare the PLR and the NLR of heart failure (HF) patients with those of age-sex matched controls, to evaluate the predictive value of those markers in detecting HF, and to demonstrate the effect of NLR and PLR on mortality in HF patients during follow-up.', 'This study included 56 HF patients and 40 controls without HF. All subjects underwent transthoracic echocardiography to evaluate cardiac functions. The NLR and the PLR were calculated as the ratio of neutrophil count to lymphocyte count and as the ratio of platelet count to lymphocyte count, respectively. All HF patients were followed after their discharge from the hospital to evaluate mortality, cerebrovascular events, and re-hospitalization.', 'The NLR and the PLR of HF patients were significantly higher compared to those of the controls (p < 0.01). There was an inverse correlation between the NLR and the left ventricular ejection fraction of the study population (r: -0.409, p < 0.001). The best cut-off value of NLR to predict HF was 3.0, with 86.3% sensitivity and 77.5% specificity, and the best cut-off value of PLR to predict HF was 137.3, with 70% sensitivity and 60% specificity. Only NLR was an independent predictor of mortality in HF patients. A cut-off value of 5.1 for NLR can predict death in HF patients with 75% sensitivity and 62% specificity during a 12.8-month follow-up period on average.",
            "output": [
                "Are neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Predictors of Heart Failure?"
            ]
        },
        {
            "id": "task847-e35965b449354fb890d0419b4720b4f0",
            "input": "Elevated intraocular pressure (IOP) is the only known modifiable risk factor for primary open angle glaucoma (POAG), and it can be caused by reduced aqueous humor outflow from the anterior chamber. Outflow is predominantly regulated by the trabecular meshwork, consisting of specialized cells within a complex extracellular matrix (ECM). An imbalance between ECM-degrading matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) within the trabecular meshwork is thought to contribute to POAG. This study aimed to quantify levels of TIMPs and MMPs in aqueous humor samples from glaucomatous and non-glaucomatous eyes, analyze MMP/TIMP ratios, and correlate results with age, IOP, and Humphrey's visual field pattern standard deviation (PSD).\", \"Aqueous humor samples were collected from 26 non-glaucomatous control subjects before cataract surgery and 23 POAG patients undergoing trabeculectomy or cataract surgery. Analyte concentrations were measured using multiplexed immunoassays. Statistical significance was assessed with Mann-Whitney U tests, and Spearman's method was used to assess correlations with age, IOP, and PSD.\", 'Concentrations of TIMP1 (p = 0.0008), TIMP2 (p = 0.002), TIMP4 (p = 0.002), and MMP2 (p = 0.020) were significantly increased in aqueous humor samples from POAG versus cataract samples. For the majority of MMP/TIMP molar ratios calculated for the cataract group, TIMPs outweighed MMPs. In POAG, molar ratios of MMP2/TIMP1 (p = 0.007) and MMP9/TIMP1 (p = 0.005) showed a significant decrease, corresponding to an elevated excess of TIMPs over MMPs in POAG compared to cataract samples. Conversely, MMP2/TIMP3 (p = 0.045) and MMP3/TIMP3 (p = 0.032) molar ratios increased. Several MMP/TIMP molar ratios correlated with IOP (r = 0.476-0.609, p = 0.007-0.034) and PSD (r = -0.482 to -0.655, p = 0.005-0.046) in POAG samples and with age in cataract control samples.",
            "output": [
                "Are tIMP1 , TIMP2 , and TIMP4 increased in aqueous humor from primary open angle glaucoma patients?"
            ]
        },
        {
            "id": "task847-bed3ea5aec744f9dac6aad667374f736",
            "input": "Na-K-Cl cotransporter 1 (NKCC1) and K-Cl cotransporter 2 (KCC2) have fundamental roles in neuron differentiation that are integrated with gamma-aminobutyric acid (GABA) and glutamate receptors, GABA synthesized by GAD25/65/67 encoded by GAD1/GAD2 genes, and GABA transporters (GATs). Cells in the eye lens express at least 13 GABA receptor subunits, \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl D-aspartate (NMDA) glutamate receptors, GAD1/GAD2, GAT1-4 and vGAT, and NKCC1. NKCC1:KCC2 ratios determine the switch in GABA actions from trophic/growth promoting early in development to their classic inhibitory roles in adult neurons. Lens epithelial cells cover the anterior surface and differentiate to elongated fiber cells in the lens interior with comparable morphology and sub-cellular structures as neurons. NKCC1 is expressed before KCC2 in neuron development and increases cell chloride, which stimulates differentiation and process formation. Subsequently, KCC2 increases and extrudes cell chloride linked with maturation. KCC2 has an additional structural moonlighting role interacting with F-actin scaffolding in dendritic spine morphogenesis. We examined KCC2 versus NKCC1 spatial expression in relation to fiber cell developmental status within the lens.', 'Immunofluorescence and immunoblots were used to detect expression in mouse and rabbit lenses.', 'NKCC1 was restricted to peripheral elongating lens fiber cells in young adult mouse and rabbit lenses. Lens KCC2 expression included the major KCC2b neuronal isoform and was detected in interior fiber cells with decreased NKCC1 expression and localized at the membranes. Lens expression of RE-1 silencing transcription factor (REST) regulated KCC2 is consistent with GAD1 and GAD2, several GABA and glutamate receptor subunits, miR-124, and other REST-regulated genes expressed in lenses.",
            "output": [
                "Does kCC2 expression supersede NKCC1 in mature fiber cells in mouse and rabbit lenses?"
            ]
        },
        {
            "id": "task847-e6f8806f509b4e7780d4c7a7557b6400",
            "input": "As first generation HCV-specific protease inhibitors, boceprevir (BOC) or telaprevir (TVR) can achieve 60% to 70% sustained virological response (SVR) for HCV infected patients with genotype 1 infections, they could remain temporary a therapeutic option in patients living in resources limited countries with limited access to the new anti-HCV direct acting antiviral (DAA) drugs, such as sofosbuvir.', 'Here we evaluated in a routine practice setting, the treatment responses, tolerance and factors associated with SVR of a triple therapy with BOC or TVR, combined with pegylated interferon and ribavirin (PegIFN/RBV) in HIV/HCV co-infected patients, included in a large cohort of HIV/HCV coinfected patients (ANRS CO13-HEPAVIH).', 'Among the 89 HIV/HCV coinfected patients treated, 65% of whom were previous non-responders to PegIFN/RBV therapy, 65%, 55% and 41% had at baseline genotype 1a, a high baseline HCV-RNA (\u2265800,000 IU/ml) and a cirrhosis, respectively. The SVR12 rate was 63% overall, 53% for BOC-based regimen and 66% for TVR-based regimen. In multivariate analysis, two factors were significantly associated with HCV SVR: HCV viral load <800,000 IU/mL at treatment initiation versus \u2265800,000 IU/mL (OR 4.403, 95% CI 1.29-15.04; p=0.018) and virological response at W4 (HCV-RNA undetectable after 4 weeks of triple therapy) (OR 3.35, 95% CI 1.07-10.48; p=0.038).",
            "output": [
                "Are hCV viral load at baseline and at week 4 of telaprevir/boceprevir based triple therapies associated with virological outcome in HIV/hepatitis C co-infected patients?"
            ]
        },
        {
            "id": "task847-bcdda1432f9e45b49cb4a227e9348a74",
            "input": "Recently, a novel clade Botrytis cinerea group S was found to be common in B. cinerea populations from Germany and New Zealand. Fenhexamid, an effective antibotrytis fungicide, has not been registered in China, but our preliminary study detected fenhexamid-resistant (HydR) isolates from strawberry in Zhejiang Province.', 'Genetic identification of 639 B. cinerea isolates from strawberry found that 331 (62.9%) belonged to B. cinerea group S. The frequency of HydR isolates ranged from 0 to 37.5% among the nine locations. Of the 74 HydR isolates, 71 were B. cinerea group S and moderately resistant to fenhexamid (HydR). Seven new mutations S9G, P57A, P269L, V365A, E368D, E375K and A378T in the target gene erg27 were reported for the first time. Sixty-two (83.8%) HydR isolates simultaneously carried P57A and A378T mutations, and further transformation assays showed that integration of one copy of erg27(P57A) (,) (A378T) into a wild-type strain led to partial resistance. Detached fruit studies showed that fenhexamid at the recommended field rate could control the disease incited by moderately resistant isolates but not by highly resistant isolates.",
            "output": [
                "Are the natural fenhexamid-resistant grey mould populations from strawberry in Zhejiang Province dominated by Botrytis cinerea group S?"
            ]
        },
        {
            "id": "task847-89bb545e76524341bec7ab8fe69baa6f",
            "input": "To investigate the genetic cause of the patients with non-syndromic enlarged vestibular aqueduct (EVA) but without bi-allelic SLC26A4 mutations.', 'Presence of a homozygous genomic deletion was detected in a Chinese Han deaf patient (D1467-1) who failed to amplify the first three exons of SLC26A4. The breakpoints of the deletion were fine-mapped and revealed by PCR amplification and sequencing. This deletion was subsequently screened in 22 Chinese Han EVA probands with mono-allelic SLC26A4 mutations. The possible founder effect of the newly identified genomic deletion was evaluated by haplotype analysis.', 'A homozygous c.-2071_307+3801del7666 deletion of SLC26A4 was identified in patient D1467-1. This novel genomic deletion was subsequently identified in 18% (4/22) of the Chinese Han EVA probands with mono-allelic SLC26A4 mutations. Haplotype analysis showed that this genomic deletion is likely a founder mutation in Chinese Hans.",
            "output": [
                "Is a 7666-bp genomic deletion frequent in Chinese Han deaf patients with non-syndromic enlarged vestibular aqueduct but without bi-allelic SLC26A4 mutations?"
            ]
        },
        {
            "id": "task847-2e7c880bd0ea466f96afaddbcccb4a2b",
            "input": "It has been shown that maternal mental health is associated with poorer skills development in the offspring. However, the evidence evaluating the association between social anxiety disorder (SAD) and cognitive or language development, is scarce.', 'To evaluate the association between maternal SAD and performance in cognitive and language tests in 30-month old children.', 'This was a cohort study involving young women evaluated since pregnancy.', 'We evaluated 520 mother-child dyads who received prenatal medical assistance through the National Public Health System in a southern Brazilian city, from October 2009 to March 2011.', 'We used the Mini Neuropsychiatric Interview Plus (MINI Plus) to assess SAD among young mothers. Cognitive and language performance in their offspring was analyzed using the Bayley Scales of Infant and Toddler Development - 3rd Edition.', 'We found an association between maternal SAD and performance in cognitive and language tests. Children of mothers with SAD had in average 4.5 less points in the Bayley scale, when compared to those with mothers without SAD: in the cognitive (\u03b2=-4.53 [95% CI -7.8; -1.1] p=0.008) and language subscales (\u03b2=-4.54 [95% CI -9.0; -0.5] p=0.047).",
            "output": [
                "Is cognitive and language performance in children associated with maternal social anxiety disorder : A study of young mothers in southern Brazil?"
            ]
        },
        {
            "id": "task847-dcbeaa2dc33d4a91acb9ac4f7a8c3fab",
            "input": "LIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder.', 'In total, four SNPs were directly genotyped. Regression models with five aggregated cognitive domains and intelligence quotient (IQ) score were run using risk variants of LMX1A (rs11809911, rs4657412, rs6668493) and NRG1 (rs35753505) as predictors. Models were performed in a clinical sample of patients with bipolar disorder (n = 114) and healthy controls (n = 104).', 'The risk variants of the rs11809911 SNP in LMX1A were negatively associated with IQ score and memory/learning, whereas the risk variants of rs35753505 in NRG1 were positively associated with IQ score (adjusted R(2) = 0.17, Q = 0.006) and memory/learning (adjusted R(2) = 0.24, Q = 0.001). The risk variants of the rs35753505 SNP in NRG1 were positively associated with language (adjusted R(2) = 0.11, Q = 0.006), visuospatial functions (adjusted R(2) = 0.23, Q = 0.001), and attention/speed (adjusted R(2) = 0.25, Q = 0.001). Results could not be replicated in controls.",
            "output": [
                "Are polymorphisms of dopamine pathway genes NRG1 and LMX1A associated with cognitive performance in bipolar disorder?"
            ]
        },
        {
            "id": "task847-e78ed8ed22cf4cf98b395ca996eb77db",
            "input": "Xenorhabdus bacteria engage in a beneficial symbiosis with Steinernema nematodes, in part by providing activities that help kill and degrade insect hosts for nutrition. Xenorhabdus strains (members of a single species) can display wide variation in host-interaction phenotypes and genetic potential indicating that strains may differ in their encoded symbiosis factors, including secreted metabolites.', 'To discern strain-level variation among symbiosis factors, and facilitate the identification of novel compounds, we performed a comparative analysis of the genomes of 10 Xenorhabdus bovienii bacterial strains.', 'The analyzed X. bovienii draft genomes are broadly similar in structure (e.g. size, GC content, number of coding sequences). Genome content analysis revealed that general classes of putative host-microbe interaction functions, such as secretion systems and toxin classes, were identified in all bacterial strains. In contrast, we observed diversity of individual genes within families (e.g. non-ribosomal peptide synthetase clusters and insecticidal toxin components), indicating the specific molecules secreted by each strain can vary. Additionally, phenotypic analysis indicates that regulation of activities (e.g. enzymes and motility) differs among strains.",
            "output": [
                "Does comparison of Xenorhabdus bovienii bacterial strain genomes reveal diversity in symbiotic functions?"
            ]
        },
        {
            "id": "task847-1a12f22013be43d19c8315c19441cd5f",
            "input": "To examine the association between insomnia with short sleep duration and hypercholesterolemia in Taiwanese adults.', 'Previous studies mostly focused on the association between sleep duration and hyperlipidemia, but the results were not consistent. Besides, very few studies extensively examined the association between insomnia and hypercholesterolemia. This study hypothesized that insomnia with short sleep duration is associated with hypercholesterolemia.', 'Secondary data analysis. This study analysed the latest database of the cross-sectional Nutrition and Health Survey in Taiwan which was released on 2011 (data collected between 2005-2008) and collected data using stratified three-staged probability sampling design.', 'This study analysed 1533 participants aged between 19-64 (733 males and 800 females) and used logistic regression model to calculate the odds ratio and the 95% confidence interval of insomnia with short sleep duration to hypercholesterolemia. Controlled confounders included age, gender, sample weight, body mass index, waist circumference, fasting plasma glucose, hypertension and diabetes.', 'Insomnia with 5-6\\xa0hours of sleep duration was significantly associated with hypercholesterolemia. The odds ratio of mild insomnia or moderate/severe insomnia with 5-6\\xa0hours of sleep duration to hypercholesterolemia was higher, compared with the reference group (without insomnia and >6\\xa0hours of sleep duration).",
            "output": [
                "Is the relationship between insomnia with short sleep duration associated with hypercholesterolemia : a cross-sectional study?"
            ]
        },
        {
            "id": "task847-bb3fae74f1454c90bf8c10c162122096",
            "input": "We hypothesize that thumb basilar joint osteoarthritis (TBJA) radiographic stage does not correlate with patient-reported measures of symptom severity.', 'Patients with unilateral TBJA who completed the 11-item QuickDASH (Disabilities of the Arm, Shoulder, and Hand), Short-Form 12 Health Survey (SF-12) Mental Component and SF-12 Physical Component surveys were prospectively enrolled in the study. The Eaton-Littler radiographic stage was assigned for each patient. The correlation between the radiographic score and disease stage was calculated.', 'Sixty-two patients (15 men, 47 women; average age, 62.3 years) formed the basis of this study. The average QuickDASH score (and standard deviation) for patients with stage 1 TBJA was 31.5 (11.4); for those with stage 2, it was 37.9 (17.4); with stage 3, it was 30.1 (13.0), and with stage 4, it was 39.4 (12.5). Eaton-Littler stage did not correlate significantly with QuickDASH scores (rho = -0.014, P = 0.91). Neither SF-12 Mental Component scores (MCS-12: rho = 0.019, P = 0.89) nor the SF-12 Physical Component scores (PCS-12: rho = 0.145, P = 0.26) correlated with TBJA stage.",
            "output": [
                "Does radiographic Stage Correlate With Symptom Severity in Thumb Basilar Joint Osteoarthritis?"
            ]
        },
        {
            "id": "task847-f716ef67e212466399a2b8dea8a938bf",
            "input": "To describe the anal cushion lifting (ACL) method with preliminary clinical results.', \"Between January to September 2007, 127 patients who received ACL method for hemorrhoid was investigated with informed consent. In this study, three surgeons who specialized in anorectal surgery performed the procedures. Patients with grade two or more severe hemorrhoids according to Goligher's classification were considered to be indicated for surgery. The patients were given the choice to undergo either the ACL method or the ligation and excision method. ACL method is an original technique for managing hemorrhoids without excision. After dissecting the anal cushion from the internal sphincter muscle, the anal cushion was lifted to oral side and ligated at the proper position. Clinical characteristics and outcomes of patients were recorded including complications after surgery.\", \"A total of 127 patients were enrolled. Their median age was 42 (19-84) years, and 74.8% were female. In addition, more than 99% of the patients had grade 3 or worse hemorrhoids. The median follow-up period was 26 (0-88) mo, and the median operative time was 15 (4-30) min. After surgery, analgesics were used for a median period of three days (0-21). Pain control was achieved using extra-oral analgesic drugs, although some patients required intravenous injections of analgesic drugs. The median duration of the patients' postoperative hospital stay was 7 (2-13) d. A total of 10 complications (7.9%) occurred. Bleeding was observed in one patient and was successfully controlled with manual compression. Urinary retention occurred in 6 patients, but it disappeared spontaneously in all cases. Recurrent hemorrhoids developed in 3 patients after 36, 47, and 61 mo, respectively. No anal stenosis or persistent anal pain occurred.",
            "output": [
                "Is anal cushion lifting method a novel radical management strategy for hemorrhoids that does not involve excision or cause postoperative anal complications?"
            ]
        },
        {
            "id": "task847-ca8d0b1d29314310bd19386ab8a96df8",
            "input": "To establish which symptoms of major depressive episode (MDE) predict postremission suicide attempts in complicated single-episode cases.', \"Using the nationally representative two-wave National Epidemiologic Survey on Alcohol and Related Conditions data set, we identified wave 1 lifetime single-episode MDE cases in which the episode remitted by the beginning of the wave 2 three-year follow-up period (N = 2791). The analytic sample was further limited to 'complicated' cases (N = 1872) known to have elevated suicide attempt rates, defined as having two or more of the following: suicidal ideation, marked role impairment, feeling worthless, psychomotor retardation, and prolonged (>6 months) duration.\", \"Logistic regression analyses showed that, after controlling for wave 1 suicide attempt which significantly predicted postremission suicide attempt (OR = 10.0), the additional complicated symptom 'feelings of worthlessness' during the wave 1 index episode significantly and very substantially predicted postremission suicide attempt (OR = 6.96). Neither wave 1 psychomotor retardation nor wave 1 suicidal ideation nor any of the other wave 1 depressive symptoms were significant predictors of wave 2 suicide attempt.",
            "output": [
                "Do feelings of worthlessness during a single complicated major depressive episode predict postremission suicide attempt?"
            ]
        },
        {
            "id": "task847-4cf26b5a34134183bbda0fd73c598d9d",
            "input": "To evaluate whether tumor invasion depth can be a reliable and easily applicable pathologic assessment strategy to predict outcomes using surgically resected cervical squamous cell carcinoma specimens from patients who have received neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).', \"We included 173 patients with cervical squamous cell carcinoma who received neoadjuvant CCRT (n\\u2009=\\u2009125) or RT (n\\u2009=\\u200948) and underwent subsequent radical hysterectomy. Data for the pre-operative clinical International Federation of Gynecology and Obstetrics (FIGO) stage, post-operative pathologic FIGO stage, World Health Organization (WHO) double diameter measurement evaluation, response evaluation criteria in solid tumors (RECIST 1.1) criteria, tumor necrosis rate (TNR), and tumor regression grade (TRG) were investigated to identify correlations with outcomes related to distant metastasis and survival. The tumor invasion depth (TID) and the tumor invasion depth with cytokeratin immunostaining correction (TIDC) at the cervical internal surface were measured to assess their relations to patients' outcomes.\", 'Based on measurements taken via transvaginal ultrasound, the pre-operative clinical and post-operative pathologic FIGO staging as well as the WHO double diameter measurement evaluation and RECIST 1.1 criteria were predictive of distant metastasis and survival-related outcomes. Also, lymph node involvement was found to be an independent prognostic factor for recurrence and distant metastasis. Finally, univariate analysis showed both the TID and TIDC were highly related to distant metastasis, overall survival, and progression-free survival, irrespective of the clinical stage of carcinomas.",
            "output": [
                "Is tumor invasion depth a useful pathologic assessment for predicting outcomes in cervical squamous cell carcinoma after neoadjuvant radiotherapy?"
            ]
        },
        {
            "id": "task847-d47fbd79f1a049beb3675cc91200f4ab",
            "input": "The objective was to evaluate whether endobronchial ultrasonography (EBUS) or endoscopic ultrasonography (EUS) staging techniques of the mediastinum for lung cancer can change the treatment plan compared with the \"gold standard\" of surgical staging.', 'Patients were retrospectively identified from a prospectively collected database. Endoscopic staging was compared with the \"gold standard\" cervical mediastinoscopy (CM). In cases where mediastinoscopy was not performed, EBUS/EUS was compared with \"ideal\" CM, a virtual procedure, which was assumed to have 100% rates of sensitivity and specificity.', 'EBUS was performed in 324 patients (99%), EUS in 295 patients (90%), and CM in 101 patients (31%); 226 patients (69%) were assumed to have undergone a virtual ideal CM and a virtual surgical mediastinal staging; 108 positive biopsies (33.0%) with endosonography had sampling of targets that were out of the scope of CM. Distant metastatic disease was diagnosed by EBUS/EUS in 7 patients (2.1%); 22 patients (6.7%) had positive targets outside the reach of the CM or virtual CM. If the 14 patients who had positive stations 5, 6, 10, and 11 are excluded (accessible with anterior mediastinotomy or extended cervical mediastinoscopy), there were 6 patients (1.8%) in whom endosonography upstaged the patient over ideal surgical mediastinal staging. In 20 patients (6.1%), ultrasound-guided biopsy made the diagnoses, which changed the treatment plan over CM and ideal CM.",
            "output": [
                "Does endoscopic Mediastinal Staging in Lung Cancer be Superior to `` Gold Standard '' Surgical Staging?"
            ]
        },
        {
            "id": "task847-e958afbd03424d85819ff23caeb6a2b4",
            "input": "Three-session days were introduced in our endoscopy unit to accommodate the increased demand resulting from the introduction of the National Health Service Bowel Cancer Screening Programme (BCSP). Cecal intubation rate (CIR) and adenoma detection rate (ADR) may decline with time during a standard working day, but data are lacking for an extended three-session day. We assessed colonoscopy performance in an extended three-session day.', 'Colonoscopies performed during the year 2011 were retrospectively analyzed. The CIR and ADR were analyzed according to the time of day when procedures were done: morning (AM), afternoon (PM), or evening (EVE). Because of an expected higher incidence of adenomas in the BCSP patients, ADR was analyzed according to indication (BCSP or non-BCSP).', 'Of the 2574 colonoscopies, 1328 (51.7\\u200a%) were in male patients and 1239 (48.3\\u200a%) in female patients with a median age of 63 years (interquartile range [IQR], 51\\u200a-\\u200a70). Of the 2574 colonoscopies, 1091 (42.4\\u200a%) were performed in AM lists, 994 (38.6\\u200a%) in PM lists, and 489 (19\\u200a%) in EVE lists. Time of day did not affect the CIRs for the AM, PM, and EVE lists (90.5\\u200a%, 90.1\\u200a%, and 89.9\\u200a%, respectively; \u03c7 (2) [2, N\\u200a=\\u200a2540]\\u200a=\\u200a0.15, P\\u200a=\\u200a0.927). The CIR was reduced in female patients and those with poor bowel preparation (P\\u200a<\\u200a0.05). After exclusion of the BCSP patients, the ADR was lower in the EVE lists than in the AM and PM lists on univariate analysis, but on multivariate analysis, this difference was not significant (P\\u200a>\\u200a0.05). The ADR was significantly higher in patients older than 60 years and in men (P\\u200a<\\u200a0.001). Queue position did not independently influence the CIR or ADR.",
            "output": [
                "Is colonoscopy performance stable during the course of an extended three-session working day?"
            ]
        },
        {
            "id": "task847-57f8b02dfe8d48d4a6e1a68e69f2ec4f",
            "input": "Carbapenem-resistant strains have been increasingly reported over the last few years. In this study we used laboratory records to determine the occurrence of carbapenem-resistant strains from hospitalized patients with emphasis on the comparative analysis of the incidence in various health-care settings.', 'From January 2012 to November 2012 and from May 2013 to November 2013, we evaluated 566 strains (Acinetobacter spp., Pseudomonas aeruginosa, Escherichia coli, and Klebsiella spp.). All isolates were tested and analyzed according to their antibiotic resistance phenotypic pattern. Laboratory results were correlated with data regarding admission in different clinical wards.', 'Among 566 isolates, 191 carbapenem-resistant or carbapenem-intermediate strains (33.74%) were detected. Non-fermentative species were the most prevalent carbapenem-resistant organisms, 80.62% of 191 carbapenem-resistant or carbapenem-intermediate strains isolated were Acinetobacter spp., and 17.27% of 191 were Pseudomonas aeruginosa. Apart from that, only 4 (2.09%) carbapenem-resistant Enterobacteriaceae (CRE) strains were identified. We identified 59.30% of 172 strains isolated from patients hospitalized in anesthesia and intensive care units non-susceptible to carbapenems. The main mechanism associated with carbapenem resistance could be the production of carbapenemase in combination with impermeability.",
            "output": [
                "Does carbapenem Resistance in Non-Fermentative Bacterial Species and in Enterobacteriaceae isolate from Hospitalized Patients in Different Health-Care Settings?"
            ]
        },
        {
            "id": "task847-158fd2e4cc1f437497f1dfa1b4c008ee",
            "input": "The incidence of thyroid cancer is increasing. As such, the number of survivors is rising, and it has been shown that their quality of life (QOL) is worse than expected. Using results from the North American Thyroid Cancer Survivorship Study (NATCSS), a large-scale survivorship study, we aim to compare the QOL of thyroid cancer survivors to the QOL of survivors of other types of cancer.', 'The NATCSS assessed QOL overall and in four subcategories: physical, psychological, social, and spiritual well-being using the QOL-Cancer Survivor (QOL-CS) instrument. Studies that used the QOL-CS to evaluate survivors of other types of cancers were compared to the NATCSS findings using two-tailed t tests.', 'We compared results from NATCSS to QOL survivorship studies in colon, glioma, breast, and gynecologic cancer. The mean overall QOL in NATCSS was 5.56 (on a scale of 0-10, where 10 is the best). Overall QOL of patients with thyroid cancer was similar to that of patients with colon cancer (mean 5.20, p\\xa0=\\xa00.13), glioma (mean 5.96, p\\xa0=\\xa00.23), and gynecologic cancer (mean 5.59, p\\xa0=\\xa00.43). It was worse than patients surveyed with breast cancer (mean 6.51, p\\xa0<\\xa00.01).",
            "output": [
                "Is quality of Life in Thyroid Cancer Similar to That of Other Cancers with Worse Survival?"
            ]
        },
        {
            "id": "task847-98195941e0fd4f9cb50c5a12a16aad76",
            "input": "Disability in older African American adults is common, but its basis is unclear. We tested the hypothesis that the level of motor function is associated with incident disability in older African Americans after adjusting for cognition.', 'A prospective observational cohort study of 605 older community-dwelling African American adults without dementia was carried out. Baseline global motor score summarized 11 motor performances, cognition was based on 19 cognitive tests, and self-reported disability was obtained annually. We examined the association of motor function with incident disability (instrumental activities of daily living [IADL], activities of daily living [ADL], and mobility disability) with a series of Cox proportional hazards models which controlled for age, sex, and education.', 'Average follow-up was about 5 years. In proportional hazards models, a 1-SD increase in baseline level of global motor score was associated with about a 50% decrease in the risk of subsequent IADL, ADL, and mobility disability (all p values < .001). These associations were unchanged in analyses controlling for cognition and other covariates. Further, the association of global motor score and incident ADL disability varied with the level of cognition (estimate -5.541, SE 1.634, p < .001), such that higher motor function was more protective at higher levels of cognition. Mobility and dexterity components of global motor score were more strongly associated with incident disability than strength (all p values < .001).",
            "output": [
                "Does motor Function be Associated With Incident Disability in Older African Americans?"
            ]
        },
        {
            "id": "task847-b852d38921d64752af7fe5c46a228219",
            "input": "Age-related decline in muscle strength is an important public health issue for older adults. Dietary protein has been associated with maintenance of muscle mass, yet its relation to muscle strength remains unclear.', 'We determined the association of dietary protein (total, animal, and plant) intake, measured by food frequency questionnaire, with change in grip strength over 6 years in 1,746 men and women from the Framingham Offspring cohort.', 'Mean age at baseline was 58.7 years (range: 29-85), and mean total, animal, and plant protein intakes were 79, 57, and 22 g/d, respectively. Adjusted baseline mean grip strength did not differ across quartiles of energy-adjusted total, animal or protein intake. Greater protein intake, regardless of source, was associated with less decrease in grip strength (all p for trend \u2264.05): participants in the lowest quartiles lost 0.17% to 0.27% per year while those in the highest quartiles gained 0.52% to 0.60% per year. In analyses stratified by age, participants aged 60 years or older (n = 646) had similar linear trends on loss of grip strength for total and animal (all p for trend <.03) but not plant protein, while the trends in participants younger than 60 years (n = 896) were not statistically significant.",
            "output": [
                "Does dietary Protein Intake be Protective Against Loss of Grip Strength Among Older Adults in the Framingham Offspring Cohort?"
            ]
        },
        {
            "id": "task847-0c70f73fe8d84d8ab605b7a0c01f21c0",
            "input": "Carotid stiffening is considered a key element in the pathogenesis of stroke. However, results of studies evaluating the association between carotid stiffness and incident stroke have been inconsistent.', 'This study investigated whether carotid stiffness (as determined by ultrasonography) is associated with incident stroke and whether this association is independent of aortic stiffness as estimated by carotid-femoral pulse wave velocity (cfPWV). Additionally, we evaluated the incremental value of carotid stiffness for stroke risk prediction beyond Framingham risk factors and cfPWV.', 'This study included a systematic review and meta-analyses of aggregate and individual participant data (IPD), the latter of which was obtained by requesting individual-level data of all cohort studies with available data on carotid stiffness and cfPWV.', 'Ten studies (n\\xa0= 22,472) were included in the aggregate data meta-analysis and 4 (n\\xa0= 4,540) in the IPD meta-analysis. After adjusting for cardiovascular (CV) factors, the aggregate data meta-analysis showed that greater carotid stiffness (per SD) was associated with stroke (hazard ratio: 1.18; 95% confidence interval: 1.05 to 1.33). In addition, carotid stiffness was associated with total CV events and CV and all-cause mortality, but not with coronary heart disease events. In the IPD meta-analysis, additional adjustment for cfPWV did not materially change these associations. Carotid stiffness did improve stroke risk prediction beyond Framingham and cfPWV (integrative discrimination improvement: 0.4 percentage point [95% confidence interval: 0.1 to 0.6 percentage point] and continuous net reclassification improvement: 18.6% [95% confidence interval: 5.8% to 31.3%]).",
            "output": [
                "Is carotid stiffness associated with incident stroke : a systematic review and individual participant data meta-analysis?"
            ]
        },
        {
            "id": "task847-e2891866a3934df4839338f4a9e163e6",
            "input": "Neocortical atrophy reduces PET signal intensity, potentially affecting the diagnostic efficacy of \u03b2-amyloid (A\u03b2) brain PET imaging. This study investigated whether partial-volume effect correction (PVEC), adjusting for this atrophy bias, improves the accuracy of (18)F-florbetaben A\u03b2 PET.', 'We analyzed (18)F-florbetaben PET and MRI data obtained from 3 cohorts. The first was 10 patients with probable Alzheimer disease (AD) and 10 age-matched healthy controls (HCs), the second was 31 subjects who underwent in vivo imaging and postmortem histopathology for A\u03b2 plaques, and the third was 5 subjects who underwent PET and MRI at baseline and 1 y later. The imaging data were coregistered and segmented. PVEC was performed using the voxel-based modified M\u00fcller-G\u00e4rtner method (PVELab, SPM8). From the PET data, regional and composite SUV ratios (SUVRs) with and without PVEC were obtained. In the MRI data, mesial temporal lobe atrophy was determined by the Scheltens mesial temporal atrophy scale and gray matter volumes by voxel-based morphometry.', 'In cohort 1, PVEC increased the effect on AD-versus-HC discrimination from a Cohen d value of 1.68 to 2.0 for composite SUVRs and from 0.04 to 1.04 for mesial temporal cortex SUVRs. The PVEC-related increase in mesial temporal cortex SUVR correlated with the Scheltens score (r = 0.84, P < 0.001), and that of composite SUVR correlated with the composite gray matter volume (r = -0.75, P < 0.001). In cohort 2, PVEC increased the correlation coefficient between mesial temporal cortex SUVR and histopathology score for A\u03b2 plaque load from 0.28 (P = 0.09) to 0.37 (P = 0.03). In cohort 3, PVEC did not affect the composite SUVR dynamics over time for the A\u03b2-negative subject. This finding was in contrast to the 4 A\u03b2-positive subjects, in 2 of whom PVEC changed the composite SUVR dynamics.",
            "output": [
                "Does partial-Volume Effect Correction improve Quantitative Analysis of 18F-Florbetaben \u03b2-Amyloid PET Scans?"
            ]
        },
        {
            "id": "task847-71465079342843569d08c3e761f781f9",
            "input": "One anesthesiologist performance metric is the incidence of \"prolonged\" (15 min or longer after dressing complete) times to extubation. The authors used several methods to identify the performance outliers and assess whether targeting these outliers for reduction could improve operating room workflow.', \"Time to extubation data were retrieved for 27,757 anesthetics and 81 faculty anesthesiologists. Provider-specific incidences of prolonged extubation were assessed by using unadjusted frequentist statistics and a Bayesian model adjusted for prone positioning, American Society of Anesthesiologist's base units, and case duration.\", '20.31% of extubations were \"prolonged,\" and 40% of anesthesiologists were identified as outliers using a frequentist approach, that is, incidence greater than upper 95% CI (20.71%). With an adjusted Bayesian model, only one anesthesiologist was deemed an outlier. If an average anesthesiologist performed all extubations, the incidence of prolonged extubations would change negligibly (to 20.67%). If the anesthesiologist with the highest incidence of prolonged extubations was replaced with an average anesthesiologist, the change was also negligible (20.01%). Variability among anesthesiologists in the incidence of prolonged extubations was significantly less than among other providers.",
            "output": [
                "Is prolonged Operative Time to Extubation a Useful Metric for Comparing the Performance of Individual Anesthesia Providers?"
            ]
        },
        {
            "id": "task847-6d431082f9d44625899843fa3046db28",
            "input": "Dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement, systolic dysfunction, and heart failure. Both genetic and non-genetic factors have been linked to DCM pathogenesis. Familial DCM (FDCM) accounts for 20%-50% of all DCM cases, highlighting the importance of genetics in pathogenesis. Indeed, more than 40 DCM-associated genes have been identified, including the gene encoding cardiac troponin T type-2 (TNNT2). We examined polymorphisms of the TNNT2 gene in idiopathic DCM (IDCM) patients of Kazak and Han ethnicity compared with healthy Kazak and Han controls.', 'Peripheral blood samples were collected from 180 patients with IDCM (90 Kazak and 90 Han), and 180 healthy controls (90 Kazak and 90 Han). PCR was used to amplify 15 exons and nearby introns of the TNNT2 gene. The amplified products were sequenced and compared to the standard sequence in PubMed by BLAST and CHROMAS software, to identify mutation sites.', 'Results from Kazak and Han IDCM patients were complied for Hardy-Weinberg equilibrium analysis. There was a significant difference in the genotype distribution (\u03c72=6.67, P=0.015) and allele frequency (\u03c72=5.71, P=0.017) between Kazaks with IDCM and Kazak controls of SNP rs3729547. There was also a difference in the genotype distribution (\u03c72=6.62, P=0.036) and allele frequency (\u03c72=4.91, P=0.018) between Han with IDCM and Han controls. The TNNT2 gene polymorphism loci rs3729547 may be associated with the IDCM onset in Kazak and Han patients (OR=2.5, 95% CI: 1.233~5.068).",
            "output": [
                "Are tNNT2 Gene Polymorphisms Associated with Susceptibility to Idiopathic Dilated Cardiomyopathy in Kazak and Han Chinese?"
            ]
        },
        {
            "id": "task847-05c3ee936f954400b48f0de13b11f471",
            "input": "To determine the frequency of nutritional deficiencies and thyroid dysfunction in children with celiac disease (CD) and during follow-up after initiation of a gluten-free diet. Laboratory investigations of hemoglobin, ferritin, calcium, folate, vitamin B12, vitamin D, and thyroid function are regularly ordered in children with CD despite sufficient evidence for these.', 'Between 2009 and 2014, test results of hemoglobin, ferritin, folate, vitamin B12, calcium, vitamin D (25[OH]D), free thyroxin, and thyroid stimulating hormone of children with CD regularly seen at the Leiden University Medical Center were investigated. Laboratory reference ranges were used to define abnormal results. Pearson \u03c7(2) test for trend, unpaired t test, and 1-way ANOVA were used for statistical analysis.', 'Of the 182 children evaluated, 119 were newly diagnosed. On average, 17% of results per year were missing because of incomplete blood investigations. Iron deficiency (28%) and iron deficiency anemia (9%) were found at the time of diagnosis of CD. Folate (14%), vitamin B12 (1%), and vitamin D deficiencies (27%) were also seen. No hypocalcemia or thyroid dysfunction was found. At follow-up, iron deficiency, iron deficiency anemia, and folate and vitamin D deficiency were observed in 8%, 2%, 3%, and 25% of patients, respectively. Vitamin B12 deficiency, hypocalcemia, and thyroid disease were not found.",
            "output": [
                "Does complementary Serologic Investigations in Children with Celiac Disease be Unnecessary during Follow-Up?"
            ]
        },
        {
            "id": "task847-b79d1fb4a25744988d7fe4b4085cce1a",
            "input": "A representative cross-sectional study showed that chronic itch (lasting for a minimum of 6 weeks) affects 25.2 % (point prevalence) of hemodialysis (HD) patients. Pathophysiology and etiology of chronic itch (CI) in HD are still unclear.', 'We investigated 860 HD patients from a representative randomly selected cluster-sample considering the regional distributions of dialysis units in Germany. The current analyses report comorbidities, laboratory values and dialysis characteristics of HD patients in relation to CI.', 'Diabetes was the only comorbidity that was associated with the occurrence of itch but interestingly with less CI. Except for creatinine, phosphorus, and parathormone, there were no significant associations between the occurrence and characteristics of CI and any laboratory value. Kt/V was not associated with the presence of CI. Patients dialyzed with polyarylethersulfone-membrane showed significantly more CI in all prevalence estimates and those dialyzed with polysulfone-membrane were significantly less affected by CI.",
            "output": [
                "Does laboratory and dialysis characteristics in hemodialysis patients suffering from chronic itch -- result from a representative cross-sectional study?"
            ]
        },
        {
            "id": "task847-60d2ec04e89a43978e0dda9c49c8edf7",
            "input": "Transfusion of red blood cells (RBCs) is a daily medical procedure. Erythrocyte concentrates (ECs) can be stored up to 56 days at 4 \u00b0C in saline additive solution mainly composed of adenine and sugar. Such nonphysiological conditions induce the occurrence of storage lesions, such as alterations of metabolism, protein oxidation, and deterioration of rheological properties. Their accumulation tends to decrease the main EC therapeutic property, that is, the oxygenation capacity. Protein carbonylation is a marker of oxidative stress and aging, and its occurrence during RBC storage was earlier characterized as a time-dependent and cellular compartment dependent modification.', 'Three ECs from independent donations were followed. The carbolynome was here characterized in soluble and membrane extracts (n-dodecyl \u03b2-D-maltoside-based extraction buffer) of RBCs stored for 6, 27, and 41 days, through biotin hydrazide derivatization, biotin-avidin affinity purification, SDS-PAGE separation, and LC-MS/MS analyses.', 'A total of 142 and 20 proteins were identified as carbonylated in soluble and membrane extracts, respectively. Particularly, a time-dependent evolution of 26.8% of the soluble carbonylome was observed.",
            "output": [
                "Does proteomics of the red blood cell carbonylome during blood banking of erythrocyte concentrate?"
            ]
        },
        {
            "id": "task847-448f3a94cc874687b8005cd22b5c4bd8",
            "input": "Insufficient insulin secretion or inefficient insulin response are responsible for the clinical outcome of type\\xa02 diabetes mellitus. Administration of insulin alone is prone to cause secondary effects, resulting in an unsatisfactory outcome. Shen-Qi-Formula (SQF), a well-known Chinese medicinal formula, has been used for diabetic treatment for a long time. The present study was designed to investigate whether SQF in combination with insulin improved the clinical outcome of type\\xa02 diabetes mellitus, and what mechanisms were possibly involved in the treatment.', 'A total of 219 patients were included in the study. Of these, 110 patients were treated with insulin monotherapy, and 109 with the combination therapy of SQF and insulin. Before and after 12-week treatment, the fasting blood glucose, postprandial blood glucose, \u03b2-cell function, insulin resistance and blood lipids were measured.', 'The 12\\xa0weeks of SQF treatment in combination with insulin significantly decreased the fasting and postprandial blood glucose levels. Insulin secretion was not increased after the treatment, but \u03b2-cell function and insulin resistance were obviously improved. Furthermore, 12\\xa0weeks of treatment with SQF and insulin improved the levels of glucagon-like peptide-1, oxidative stress, blood lipids, coagulation function and bodyweight.",
            "output": [
                "Does insulin combined with Chinese medicine improve glycemic outcome through multiple pathways in patients with type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-162b3641280245cf88a126088fdd8b86",
            "input": "Greater glycemic variability and lack of predictability are important issues for patients with type 1 diabetes. Dietary factors are one of the contributors to this variability, but how closely diet is linked to glycemic fluctuation on a daily basis has not been investigated. We examined the association between carbohydrate intake and glycemic excursion in outpatients.', 'A total of 33 patients with type 1 diabetes were included in the analyses (age 44.5\\xa0\u00b1\\xa014.7\\xa0years, diabetes duration 15.1\\xa0\u00b1\\xa08.3\\xa0years, 64% female, 30% using insulin pump, glycated hemoglobin 8.1\\xa0\u00b1\\xa01.3%). Time spent in euglycemia (70-180\\xa0mg/dL), hyperglycemia (>180\\xa0mg/dL) and hypoglycemia (<70\\xa0mg/dL) of consecutive 48-h periods of continuous glucose monitoring data were collected together with simultaneous records of dietary intake, insulin dose and physical activity. Correlation analyses and multiple regression analyses were used to evaluate the contribution of carbohydrate intake to time spent in the target glycemic range.', 'In multiple regression analyses, carbohydrate intake (\u03b2\\xa0=\\xa00.53, P\\xa0=\\xa00.001), basal insulin dose per kg per day (\u03b2\\xa0=\\xa0-0.31, P\\xa0=\\xa00.034) and diabetes duration (\u03b2\\xa0=\\xa00.30, P\\xa0=\\xa00.042) were independent predictors of time spent in euglycemia. Carbohydrate intake (\u03b2\\xa0=\\xa0-0.51, P\\xa0=\\xa00.001) and insulin pump use (\u03b2\\xa0=\\xa0-0.34, P\\xa0=\\xa00.024) were independent predictors of time spent in hyperglycemia. Insulin pump use (\u03b2\\xa0=\\xa00.52, P\\xa0<\\xa00.001) and bolus insulin dose per kg per day (\u03b2\\xa0=\\xa00.46, P\\xa0=\\xa00.001) were independent predictors of time spent in hypoglycemia.",
            "output": [
                "Is carbohydrate intake associated with time spent in the euglycemic range in patients with type 1 diabetes?"
            ]
        },
        {
            "id": "task847-3b329f0589324c908e04a9cd0f7f5995",
            "input": "In patients undergoing elective partial pancreatectomy, our aim was to evaluate the effect of metabolic syndrome (MS) on postoperative mortality, morbidity, and utilization of hospital resources. Our hypothesis was that MS is associated with worse surgical outcomes after pancreatectomy.', 'Fifteen thousand eight hundred thirty-one patients undergoing elective pancreatectomy from 2005 to 2012 were identified in the Participant User File of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Univariable and multivariable analyses were performed examining the association of MS (defined as body mass index \u226530 kg/m(2), hypertension requiring medications, and diabetes requiring medications and/or insulin) and risk of 30-day mortality, morbidity, and utilization of hospital resources (risk of blood transfusion in the first 72 h after pancreatectomy and prolonged hospital stay, defined as \u226513 days, which was the 75th percentile of this cohort). Multivariable logistic regression models controlled for age, sex, race, pancreatectomy type (distal versus proximal), smoking status, alcohol consumption, functional status, dyspnea, cardiovascular disease, hematocrit, INR, serum albumin, bilirubin, and creatinine. Stratified analyses were conducted by type of pancreatectomy and indication for pancreatectomy (benign versus malignant).', 'On univariate analysis, 1070 (6.8%) patients had MS. MS was associated with increased postoperative morbidity, major morbidity, surgical site infection, septic shock, cardiac event, respiratory failure, pulmonary embolism, blood transfusion, and prolonged duration of hospital stay (P\\u2009<\\u20090.05 for all analyses). After controlling for potentially confounding variables, there was a 26% increased odds of postoperative morbidity (P\\u2009<\\u20090.001), 17% increased odds of major morbidity (P\\u2009=\\u20090.034), 32% increased odds of surgical site infection (P\\u2009<\\u20090.001), 34% increased odds of respiratory failure (P\\u2009=\\u20090.023), 68% increased odds of pulmonary embolism (P\\u2009=\\u20090.045), 26% increased odds of blood transfusion (P\\u2009=\\u20090.018), and 21% increased odds of prolonged hospital stay (P\\u2009=\\u20090.011) in patients with MS compared to patients without MS. MS was not associated with 30-day mortality after elective pancreatectomy (P\\u2009=\\u20090.465). When stratified by distal versus proximal pancreatectomy and benign versus malignant disease, the effect of MS on outcomes appears to be modified by type of pancreatectomy and indication with poorer outcomes observed for distal pancreatectomies and benign indications for resection.",
            "output": [
                "Is metabolic Syndrome Associated with Increased Postoperative Morbidity and Hospital Resource Utilization in Patients Undergoing Elective Pancreatectomy?"
            ]
        },
        {
            "id": "task847-c41d29971cec4d68b07e82d2dbc50912",
            "input": "to investigate the origin characters of snore in simple snorers and provide the basis for its treatment.', 'Thirty-two simple snorers diagnosed by polysomnography were induced to sleep by propofol and dexmedetomidine, then we observed the vibration sites, pattern and concomitant collapse of soft tissue in pharyngeal cavity by nasendoscopy.', 'Thirteen cases showed palatal fluttering only, and 1 case showed vibration of epiglottis only. Six cases showed palatal fluttering with vibration of epiglottis, and 2 cases showed palatal fluttering with vibration of epiglottis and tongue base. Five cases showed palatal fluttering with vibration of pharyngeal lateral wall, and 5 cases showed palatal fluttering with vibration of lateral wall, epiglottis and tongue base together. Palate and pharyngeal lateral wall vibrated strongly and always collapsed with vibrating, but epiglottis and tongue base usually vibrated slightly and seldom collapsed.",
            "output": [
                "Do [ The preliminary study of the origin characters of snore in simple snorers ]?"
            ]
        },
        {
            "id": "task847-39f984470f774357a65e5fd45b67d88a",
            "input": "considering the frequent consumption of fat-rich diets by women of reproductive age, the aim of the present study was to investigate the effects of maternal consumption of a high-fat diet during the perinatal and/ or post-weaning period on the liver parameters and lipid metabolism of young rats.', 'Wistar female rats were fed a high-fat (H) or control (C) diet during pregnancy and lactation. The offspring were allocated to four groups: Control Control (CC, n = 11), offspring fed a control diet after weaning; Control High-fat (CH, n = 10), offspring fed a high-fat diet after weaning; High-fat High-fat (HH, n = 10), offspring of mothers H fed a high-fat diet after weaning; and High-fat Control (HC, n = 9), offspring of mothers H fed with control diet after weaning.",
            "output": [
                "Does mATERNAL AND POST-WEANING EXPOSURE TO A HIGH FAT DIET promote VISCERAL OBESITY AND HEPATIC STEATOSIS IN ADULT RATS?"
            ]
        },
        {
            "id": "task847-6cefd9ee3b1f49288778179f7ce4d6bc",
            "input": "Stroke is a leading cause of long-term disability. Currently, there are no consistently effective rehabilitative treatments for chronic stroke patients. Our recent studies demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training improves recovery of function in multiple models of stroke. Here, we evaluated the ability of VNS paired with rehabilitative training to improve recovery of forelimb strength when initiated many weeks after a cortical and subcortical ischemic lesion in subjects with stable, chronic motor deficits.', 'Rats were trained to perform an automated, quantitative measure of voluntary forelimb strength. Once proficient, rats received injections of endothelin-1 to cause a unilateral cortical and subcortical ischemic lesion. Then, 6 weeks after the lesion, rats underwent rehabilitative training paired with VNS (Paired VNS; n = 10), rehabilitative training with equivalent VNS delivered 2 hours after daily rehabilitative training (Delayed VNS; n = 10), or rehabilitative training without VNS (Rehab, n = 9).', 'VNS paired with rehabilitative training significantly improved recovery of forelimb function compared with control groups. The Paired VNS group displayed an 86% recovery of strength, the Rehab group exhibited 47% recovery, and the Delayed VNS group exhibited 42% recovery. Improvement in forelimb function was sustained in the Paired VNS group after the cessation of stimulation, potentially indicating lasting benefits. No differences in intensity of rehabilitative training, lesion size, or MAP-2 expression were observed between groups.",
            "output": [
                "Does vagus Nerve Stimulation During Rehabilitative Training improve Forelimb Recovery After Chronic Ischemic Stroke in Rats?"
            ]
        },
        {
            "id": "task847-fbb99f9e0eff4feeb51092635fb9bb4f",
            "input": "We study the Azospirillum brasilense tolerance to water deficit and the dynamics of adaptive process at the level of the membrane.', 'Azospirillum brasilense was exposed to polyethylene glycol (PEG) growth and PEG shock. Tolerance, phospholipids and fatty acid (FA) composition and membrane fluidity were determined. Azospirillum brasilense was able to grow in the presence of PEG; however, its viability was reduced. Cells grown with PEG showed membrane fluidity similar to those grown without, the lipid composition was modified, increasing phosphatidylcholine and decreasing phosphatidylethanolamine amounts. The unsaturation FAs degree was reduced. The dynamics of the adaptive response revealed a decrease in fluidity 20\\xa0min after the addition of PEG, indicating that the PEG has a fluidizing effect on the hydrophobic region of the cell membrane. Fluidity returned to initial values after 60\\xa0min of PEG exposure.",
            "output": [
                "Is reorganization of Azospirillum brasilense cell membrane mediated by lipid composition adjustment to maintain optimal fluidity during water deficit?"
            ]
        },
        {
            "id": "task847-184b26860bc446669d2571de7bbf06e4",
            "input": "Among virally suppressed HIV-infected persons, we examined the relationship between obesity and alterations in key clinical markers of immune activation and inflammation. These markers have also been associated with excess HIV-related cardiovascular disease and mortality.', 'We evaluated data from virally suppressed participants in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy, including inflammatory biomarkers (interleukin-6 and highly sensitive C-reactive protein), monocyte biomarkers [soluble CD163 (sCD163), sCD14], and monocyte immunophenotypes. We assessed associations with these immunologic measures and obesity, via logistic regression preadjustment and postadjustment for demographic and clinical factors, homeostatic model assessment of insulin resistance, and leptin levels.', 'Among 452 evaluable participants, median (interquartile range) age was 41 (36-48) years, CD4 cell count was 475 (308-697)\\u200acells/\u03bcl, and 21% were obese (BMI \u2265 30\\u200akg/m). In univariable models, obesity, smoking, and lower CD4 cell count were associated with higher measures of inflammation and monocyte activation. After adjustment, obesity remained independently associated with elevated levels (highest vs. lower two tertiles) of interleukin-6 [odds ratio (OR) 1.96; P = 0.02], highly sensitive C-reactive protein (OR 2.79; P\\u200a<\\u200a0.001) and sCD163 (OR 1.94; P\\u200a=\\u200a0.02), and elevated frequency of CD14CD16 (OR 1.77; P\\u200a=\\u200a0.03) and CD14dimCD16 (OR 1.97; P\\u200a=\\u200a0.01). Adjusting for homeostatic model assessment of insulin resistance and leptin modestly affected associations for obesity with inflammation and monocyte activation.",
            "output": [
                "Is obesity associated with greater inflammation and monocyte activation among HIV-infected adults receiving antiretroviral therapy?"
            ]
        },
        {
            "id": "task847-61838761b1e44b3d890ad872f98fb3c5",
            "input": "Dexamethasone (Dex)-induced spontaneous tendon rupture and decreased self-repair capability is very common in clinical practice. The metaplasia of adipose tissue in the ruptured tendon indicates that Dex may induce tendon stem cells (TSCs) to differentiate into adipocytes, but the mechanism remains unclear. In the present study, we used in vitro methods to investigate the effects of Dex on rat TSC differentiation and the molecular mechanisms underlying this process.', 'First, we used qPCR and Western blotting to detect the expression of the adipogenic differentiation markers aP2 and C/EBP\u03b1 after treating the TSCs with Dex. Oil red staining was used to confirm that high concentration Dex promoted adipogenic differentiation of rat TSCs. Next, we used qPCR and Western blotting to detect the effect of a high concentration of dexamethasone on molecules related to the canonical WNT/\u03b2-catenin pathway in TSCs.', 'Treating rat TSCs with Dex promoted the synthesis of the inhibitory molecule dickkopf1 (DKK1) at the mRNA and protein levels. Western blotting results further showed that Dex downregulated the cellular signaling molecule phosphorylated glycogen synthase kinase-3\u03b2 (P-GSK-3 \u03b2 (ser9)), upregulated P-GSK-3\u03b2 (tyr216), and downregulated the pivotal signaling molecule \u03b2-catenin. Furthermore, DKK1 knockdown attenuated Dex-induced inhibition of the canonical WNT/\u03b2-catenin pathway and of the adipogenic differentiation of TSCs. Lithium chloride (LiCl, a GSK-3\u03b2 inhibitor) reduced Dex-induced inhibition of the classical WNT/\u03b2-catenin pathway in TSCs and of the differentiation of TSCs to adipocytes.",
            "output": [
                "Does dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone promote Rat Tendon Stem Cells to Differentiate Into Adipocytes?"
            ]
        },
        {
            "id": "task847-3d3ce0b5fc8245c89383043f153f4f0c",
            "input": "IL-1\u03b2 plays a vital role in the terminal processes of human labour and delivery. Inflammasome activation is required to process pro IL-1\u03b2 to an active, secreted molecule. Recent studies have shown that autophagy regulates IL-1\u03b2 via the inflammasome. The aims were to determine the effect of (i) human spontaneous term and preterm labour on the expression of autophagy proteins in fetal membranes; and (ii) autophagy inhibition on IL-1\u03b2 release.', 'Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women. Tissue explants were used to determine the effect of inhibition of autophagy on IL-1\u03b2 secretion.', 'Expression of the autophagy proteins Beclin-1, Atg3, Atg5, Atg7, Atg12, Atg16L1 were lower after spontaneous term labour. Beclin-1 and Atg7 expression were lower after spontaneous preterm labour. Beclin-1, Atg3, and Atg7 expression were lower after preterm pre-labour rupture of membranes (PPROM) compared to preterm with intact membranes. LC3B-I expression was higher after spontaneous term and preterm labour and with PPROM; there was no difference in LC3B-II expression between the two groups. The autophagy inhibitor LY290042 increased IL-1\u03b2 secretion in the presence of bacterial endotoxin LPS; IL-1\u03b2 secretion was ameliorated in the presence inflammasome inhibitors.",
            "output": [
                "Is autophagy , which decreased in labouring fetal membranes , regulates IL-1\u03b2 production via the inflammasome?"
            ]
        },
        {
            "id": "task847-b3dee8d09050493e911eadb4d5196643",
            "input": "Sepsis from burn injuries can result from colonisation of burn wounds, especially in large surface area burns. Reducing bacterial infection will reduce morbidity and mortality, and mortality for severe burns can be as high as 15\\xa0%. There are various quantitative and semi-quantitative techniques to monitor bacterial load on wounds. In the UK, burn wounds are typically monitored for the presence or absence of bacteria through the collection and culture of swabs, but no absolute count is obtained. Quantitative burn wound culture provides a measure of bacterial count and is gaining increased popularity in some countries. It is however more resource intensive, and evidence for its utility appears to be inconsistent. This systematic review therefore aims to assess the evidence on the utility and reliability of different quantitative microbiology techniques in terms of diagnosing or predicting clinical outcomes.', 'Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Bibliographic databases and ongoing trial registers will be searched and conference abstracts screened. Studies will be eligible if they are prospective studies or systematic reviews of burn patients (any age) for whom quantitative microbiology has been performed, whether it is compared to another method. Quality assessment will be based on quality assessment tools for diagnostic and prognostic studies and tailored to the review as necessary. Synthesis is likely to be primarily narrative, but meta-analysis may be considered where clinical and methodological homogeneity exists.",
            "output": [
                "Do protocol for a systematic review of quantitative burn wound microbiology in the management of burns patients?"
            ]
        },
        {
            "id": "task847-f6a2843bc0d24e969fe758470f5cee74",
            "input": "To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA).', \"We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with \u22651 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models.\", 'Of 113\\u2005677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6\\u2005months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6\\u2005months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged \u226550\\u2005years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3\\u2005years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively.",
            "output": [
                "Are longer durations of antitumour necrosis factor treatment associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-95a9bdaea3a54c0db2b9b8c8739d39ca",
            "input": "Hepatitis B s antigen (HBsAg) seroclearance is regarded as the optimal virological end-point.', 'To investigate the dynamic changes in serum cytokine levels around the time of HBsAg seroclearance.', 'This was a case-control study. Consecutive patients with chronic hepatitis B (CHB) who lost HBsAg were matched with those remained positive for HBsAg with same age, gender, HBeAg status and presence of cirrhosis in 1:2 ratio. Relevant serum cytokines [interleukin (IL)-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, IL-15, IL-21 interferon-\u03b3, tumour necrosis factor-\u03b1 (TNF-\u03b1), granulocyte macrophage colony-stimulating factor (GM-CSF) and interferon-inducible protein 10 (IP-10)] were assayed at the time (Year 0) and 3 years before (Year -3) HBsAg seroclearance.', 'Seventy-one and 142 CHB patients who did and did not achieve HBsAg seroclearance were included. Mean age was 48 \u00b1 11 years; 76% were male, 20% had positive HBeAg, 99 (46%) patients received anti-viral therapy, and mean baseline HBV DNA was 3.78 \u00b1 2.28 log IU/mL vs. 4.36 \u00b1 2.13 log IU/mL respectively (P = 0.05). In those who achieved HBsAg seroclearance, serum IL-15 and GM-CSF levels decreased significantly from Year -3 to Year 0 (P = 0.017 and 0.05 respectively). When compared to controls, only serum IP-10 level was significantly lower at Year 0 than at Year -3 in patients with HBsAg seroclearance. Lower serum IP-10 level at Year 0 was the only factor associated with HBsAg seroclearance. There was no correlation between serum IP-10 and HBsAg levels around the time of HBsAg seroclearance.",
            "output": [
                "Do serum interferon-inducible protein 10 levels predict hepatitis B s antigen seroclearance in patients with chronic hepatitis B?"
            ]
        },
        {
            "id": "task847-ada5cefb5c4b4f3a9be181e0db25be69",
            "input": "Maraviroc (MVC) is a potential candidate for 'on demand' preexposure prophylaxis. In the present study, we evaluated the efficacy of a single oral dose of MVC to prevent ex-vivo HIV-1 infection of rectal tissue in humans.\", 'Eight HIV-1-negative healthy volunteers received a single oral dose of MVC (300 or 600\\u200amg), and two additional volunteers received tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 300/200\\u200amg) for 10 days. Rectal biopsies were performed prior to the ex-vivo challenge (day 0), at day 7 (4\\u200ah after MVC) or after 10 days with TDF/FTC. Rectal biopsies were infected ex-vivo, and viral inhibition and CCR5 occupancy was analyzed. MVC concentration in plasma and rectal tissue was measured just after biopsy and after viral incubation.', 'Ex-vivo rectal tissue protection with MVC was incomplete in all but two participants, whereas TDF/FTC avoided ex-vivo infection in the two controls. Median dose-normalized concentration of MVC was significantly higher in rectal tissue than in plasma (561.1 and 155.1\\u200ang/ml, respectively). A significant loss of MVC during the virus incubation (about 60%) and a low CCR5 occupancy (approximately 45%) were detected in rectal cells.",
            "output": [
                "Does single oral dose of maraviroc prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers?"
            ]
        },
        {
            "id": "task847-b37578e24d864cdfb25ed349378e6580",
            "input": "Mannose-binding lectin (MBL) is a key component of innate immunity. The expression of cortical MBL is up-regulated after clinical and experimental head trauma. This study aimed to assess the association of serum MBL levels with injury severity and long-term clinical outcomes after severe traumatic brain injury (STBI).', 'Serum MBL levels were measured in 122 patients and 100 healthy controls. Multivariate analyses were used to analyze the relationship between serum MBL levels and trauma severity reflected by Glasgow Coma Scale scores as well as between serum MBL levels and 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score: 1-3). A receiver operating characteristic (ROC) curve was structured to evaluate the prognostic predictive performance of serum MBL levels.', 'Compared with healthy controls, serum MBL levels of patients were markedly elevated. Using multivariate analyses, serum MBL levels were found to be associated closely with Glasgow Coma Scale (GCS) scores and MBL emerged as an independent predictor for 6-month mortality and unfavorable outcome. Under ROC curve, serum MBL levels and GCS scores possessed similar prognostic predictive values.",
            "output": [
                "Are high levels of serum mannose-binding lectins associated with the severity and clinical outcomes of severe traumatic brain injury?"
            ]
        },
        {
            "id": "task847-b7f162eb1eae4bfc997e0ec6e4141c76",
            "input": "A polymorphism (C825T) in G-protein \u03b2 polypeptide-3 (GN\u03b23) gene alters intracellular signal transduction, which may cause motor or sensory abnormalities in the gastrointestinal tract. Cholecystokinin-A receptor (CCK-AR) gene T/C polymorphism is associated with a defective splicing of the primary transcript of CCK-AR mRNA, which may modulate satiety signal and delay gastric emptying. Therefore, we evaluated the role of these polymorphisms in patients with functional dyspepsia (FD) as compared with healthy controls (HC).', 'A total of 237 consecutive patients with FD (Rome III) and 250 HC were genotyped for GN\u03b23 C825T and CCK-AR T/C polymorphisms (PCR-RFLP).', 'Patients with FD [173 (73%) men, age: 38 \u00b1 12 years] were comparable with HC [195 (78%) men, age: 37 \u00b1 12 years] with respect to age and sex. Out of 237 patients, 26 (11%) had epigastric pain syndrome (EPS), 55 (23.2%) had postprandial distress syndrome (PDS), and 156 (65.8%) had EPS-PDS overlap. Among 237 patients with FD, TT genotype (associated with increased intracellular signal transduction) of GN\u03b23 C825T polymorphism was more common among patients than among HC [26 (11%) vs. 12 (4.8%), P=0.014; odds ratio (OR): 2.47, 95% confidence interval (CI): 1.2-5.1]. CC (variant) genotype of CCK-AR T/C polymorphism was infrequent among patients than among HC [19 (8%) vs. 46 (18.4%), P=0.001; OR: 0.36, 95% CI: 0.19-0.66]. However, these polymorphisms were comparable among patients with different subtypes of FD (P=0.80 and 0.44).",
            "output": [
                "Is functional dyspepsia associated with GN\u03b23 C825T and CCK-AR T/C polymorphism?"
            ]
        },
        {
            "id": "task847-794f988a97064bb5a0cbecddb9510b90",
            "input": "An association between obesity and otitis media with effusion (OME) has been previously reported. The aim of this study was to evaluate the association between dietary intake and OME when adjusting obesity.', 'We analyzed the differences in dietary intake between children with/without OME who were 4 through 13 years of age using data from a large population-based survey - the Korea National Health and Nutrition Examination Survey - from 2008 through 2012. Data from 4359 participants were analyzed using simple and multiple logistic regression analyses with complex sampling.', 'The BMI category, the proportion of total calorie intake, protein intake, water intake, and Na intake (intake/recommendation), and the distribution of carbohydrate intake were not associated with OME. The distribution of fat intake was associated with OME (each 10% increase of fat calories/total calories: unadjusted odds ratio [OR]=1.331, 95% confidence interval [CI]=1.016-1.744, P=0.038; age- and sex-adjusted OR=1.359, 95% CI=1.028-1.797, P=0.031; adjusted for age, sex and other factors OR=1.392, 95% CI=1.054-1.839, P=0.020). Based on BMI subgroup analysis, the distribution of fat intake was associated with OME in the healthy weight group (each 10% increase of fat calories/total calories: unadjusted OR=1.393, 95% CI=1.017-1.909, P=0.039; adjusted OR=1.470, 95% CI=1.051-2.055, P=0.024) but not in the obese group.",
            "output": [
                "Is a high-fat diet associated with otitis media with effusion?"
            ]
        },
        {
            "id": "task847-52792adc25e74d2fbf44be85019bc2bd",
            "input": "Congenital factor VII (FVII) and factor X (FX) deficiencies belong to the group of rare bleeding disorders which may occur in separate or combined forms since both the F7 and F10 genes are located in close proximity on the distal long arm of chromosome 13 (13q34). We here present data of 192 consecutive index cases with FVII and/or FX deficiency. 10 novel and 53 recurrent sequence alterations were identified in the F7 gene and 5 novel as well as 11\\xa0recurrent in the F10 gene including one homozygous 4.35\\xa0kb deletion within F7 (c.64+430_131-6delinsTCGTAA) and three large heterozygous deletions involving both the F7 and F10 genes. One of the latter proved to be cytogenetically visible as a chromosome 13q34 deletion and associated with agenesis of the corpus callosum and psychomotor retardation.",
            "output": [
                "Do large deletions play a minor but essential role in congenital coagulation factor VII and X deficiencies?"
            ]
        },
        {
            "id": "task847-d545ce98206c49e898a5c1f2aae8fe27",
            "input": "Various surgical techniques to treat posterolateral knee instability have been described. To date, the recommended treatment is an anatomic form of reconstruction in which the 3 key structures of the posterolateral corner (PLC) are addressed: the popliteofibular ligament, the popliteus tendon, and the lateral collateral ligament.', 'The purpose of this study was to identify the role of each key structure of the PLC in kinematics of the knee and to biomechanically analyze a single-graft, fibular-based reconstruction that replicates the femoral insertions of the lateral collateral ligament and popliteus to repair the PLC. The hypothesis was that knee kinematics can be reasonably restored using a single graft with a 2-strand \"modified Larson\" technique.', 'Descriptive laboratory study.', 'Eight fresh-frozen cadaveric knees were used in this study. We conducted sequential sectioning of the popliteofibular ligament (PFL) and then subsequently the popliteal tendon (PT), the lateral collateral ligament (LCL), and the anterior cruciate ligament (ACL). We then reconstructed the ACL first and then the posterolateral corner using the modified Larson technique. A surgical navigation system was used to measure varus laxity and external rotation at 0\u00b0, 30\u00b0, 60\u00b0, and 90\u00b0 with a 9.8-N\u00b7m varus stress and 5-N\u00b7m external rotation force applied to the tibia.', 'In extension, varus laxity increased only after the sectioning of the lateral collateral ligament. At 30\u00b0 of flexion, external rotation in varus and translation of the lateral tibial plateau increased after the isolated popliteofibular ligament section. From 60\u00b0 to 90\u00b0 of flexion, translation and mobility of the lateral plateau section increased after sectioning of the PFL. After reconstruction, we observed a restoration of external varus rotation in extension and translation of the lateral tibial plateau at 90\u00b0 of flexion. This technique provided kinematics similar to the normal knee.",
            "output": [
                "Does reconstruction of the Posterolateral Corner After Sequential Sectioning restore Knee Kinematics?"
            ]
        },
        {
            "id": "task847-e1c4d85ae4ef4bd488f13bb301225e74",
            "input": "The clinical effects of a pre-fixed flow of air-oxygen versus a flow titrated according to visible bubbling are not well understood.', 'To compare the effects of a fixed flow (5\\u2009L/min) and titrated flow (flow just enough to ensure bubbling) at different set pressures on delivered intra-prong pressure, gas exchange and clinical parameters in preterm infants on bubble CPAP for respiratory distress.', 'Preterm infants <35 weeks gestational age on bubble CPAP and <96 h of age were enrolled in this crossover study. They were subjected to 30-min periods of titrated flow and fixed flow. At the end of both epochs, gas flow rate, set pressure, FiO2, SpO2, Silverman retraction score, respiratory rate, abdominal girth, and blood gases were recorded. The delivered intra-prong pressure was measured by an electronic manometer.', '69 recordings were made in 54 infants. For each of the set CPAP pressures (4, 5, and 6\\u2009cm H2O), the mean delivered pressure with a fixed flow of 5\\u2009L/min was higher than that delivered by the titrated flow. During the fixed flow epoch, the delivered pressure was closer to and higher than the set pressure resulting in higher PaO2 and lower PaCO2 as compared to titrated flow epoch. In the titrated flow period, the delivered pressure was consistently lower than the set pressure.",
            "output": [
                "Is a Fixed Flow More Effective than Titrated Flow during Bubble Nasal CPAP for Respiratory Distress in Preterm Neonates?"
            ]
        },
        {
            "id": "task847-c3cd8f3319a84f9eaa68c68426498655",
            "input": "To investigate the effects of crypotanshinone (CPT) on the proliferation and apoptosis of DU145 prostate cancer cells as well as on the metadherin expression and the downstream PI3K/AKT signaling pathway in the DU145 cells.', 'We treated DU145 prostate cancer cells with different concentrations of CPT for 24, 48, and 72 hours followed by evaluation of the proliferation and apoptosis of the cells by MTT assay and TUNEL, respectively. We determined the expressions of metadherin protein and mRNA in the DU145 cells by Western blot and RT-PCR respectively at different time points after CPT treatment. We also detected the expressions of the proteins metadherin, AKT, p-AKT, and Bcl-2 in the CPT-treated DU145 cells at 48 hours.', 'CPT significantly inhibited the proliferation of the DU145 cells in a dose- and time-dependent manner (P < 0.05). After treatment with 10 \u00b5mol/L CPT for 24, 48, and 72 hours, the apoptosis rates of the DU145 cells were (29.42 \u00b1 4.51), (55.07 \u00b1 5.67) and (70.84 \u00b1 4.66)%, respectively, significantly higher than (3.1 \u00b1 2.48)% in the control group (P < 0.05). The expression of metadherin was remarkably downregulated at the transcription and translation levels (P < 0.05) and the expressions of the AKT signaling pathway and the Bcl-2 protein were markedly inhibited in the DU145 cells after treated with 10 \u00b5mol/L CPT for 48 hours (P < 0.05).",
            "output": [
                "Does [ Crypotanshione reduce the expression of metadherin in DU145 prostate cancer cells ]?"
            ]
        },
        {
            "id": "task847-e832cfc4a2814040afd653aba9a30976",
            "input": "Intracerebral hemorrhage (ICH) induces microglial activation and the release of inflammatory cytokines, leading to inflammation in the brain. IRAK4, an essential component of the MyD88-dependent pathway, activates subsets of divergent signaling pathways in inflammation.', 'In the experiment, microglia were stimulated with erythrocyte lysates, and then miR-367, IRAK4, NF-\u0138B activation and downstream proinflammatory mediator production were analyzed. In addition, inflammation, brain edema, and neurological functions in ICH mice were also assessed.', \"Here, we report that ICH downregulated miR-367 expression but upregulated IRAK4 expression in primary microglia. We also demonstrate that miR-367 suppressed IRAK4 expression by directly binding its 3'-untranslated region. MiR-367 inhibited NF-\u0138B activation and downstream proinflammatory mediator production. Knocking down IRAK4 in microglia significantly decreased the IRAK4 expression and inhibited the NF-\u0138B activation and the downstream production of proinflammatory mediators. In addition, our results indicate that miR-367 could inhibit expression of proinflammatory cytokines, reduce brain edema, and improve neurological functions in ICH mice.",
            "output": [
                "Does microRNA367 negatively regulate the inflammatory response of microglia by targeting IRAK4 in intracerebral hemorrhage?"
            ]
        },
        {
            "id": "task847-14f1887459fd412598b69ed242b47bbe",
            "input": "The aim of this study was to evaluate whether percutaneous transhepatic biliary drainage (PTBD) increases the incidence of seeding metastasis and shortens postoperative survival compared with endoscopic biliary drainage (EBD).', 'A total of 376 patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy following either PTBD (n\\xa0=\\xa0189) or EBD (n\\xa0=\\xa0187) at 30 hospitals between 2001 and 2010 were retrospectively reviewed. Seeding metastasis was defined as peritoneal/pleural dissemination and PTBD sinus tract recurrence. Univariate and multivariate analyses followed by propensity score matching analysis were performed to adjust the data for the baseline characteristics between the two groups.', 'The overall survival of the PTBD group was significantly shorter than that of the EBD group (34.2\\xa0% vs 48.8\\xa0% at 5\\xa0years; P\\xa0=\\xa00.003); multivariate analysis showed that the type of biliary drainage was an independent predictor of survival (P\\xa0=\\xa00.036) and seeding metastasis (P\\xa0=\\xa00.001). After two new cohorts with 82 patients each has been generated after 1:1 propensity score matching, the overall survival rate in the PTBD group was significantly less than that in the EBD group (34.7\\xa0% vs 52.5\\xa0% at 5\\xa0years, P\\xa0=\\xa00.017). The estimated recurrence rate of seeding metastasis was significantly higher in the PTBD group than in the EBD group (30.7\\xa0% vs 10.7\\xa0% at 5\\xa0years, P\\xa0=\\xa00.006), whereas the recurrence rates at other sites were similar between the two groups (P\\xa0=\\xa00.579).",
            "output": [
                "Is percutaneous biliary drainage oncologically inferior to endoscopic drainage : a propensity score matching analysis in resectable distal cholangiocarcinoma?"
            ]
        },
        {
            "id": "task847-81b67518bb0c48dea05f02bbf835258f",
            "input": "This study was performed to examine the characteristics of indoor and outdoor falls in older patients and the factors related to severe injury in the emergency department (ED).', 'In total, 26,515 patients fell indoors and 19,581 outdoors. The general and clinical characteristics were compared between the two groups and factors associated with severe injury following the falls were evaluated.', 'Younger males fell more frequently outdoors than indoors. The common activities during outdoor falls were sports and leisure activities. Environmental hazards lead to more outdoor falls than indoor falls. Factors associated with severe injury after indoor falls were transport to the ED by public ambulance or from another medical facility rather than individual transportation, fall from stairs rather than fell over, and a head and neck injury rather than a lower extremity injury. Factors related to severe injury after outdoor falls were male sex, transport to the ED by public ambulance or from another medical facility or by another method rather than individual transportation, state employed, fall from stairs rather than fell over, head and neck or thorax or abdomen injury rather than a lower extremity injury.",
            "output": [
                "Does risk factors for severe injury following indoor and outdoor fall in geriatric patients?"
            ]
        },
        {
            "id": "task847-ce36f1aae2fe4ab3baaff8ade7189d92",
            "input": "Sensory impairment affects an increasing number of elderly adults, with a negative psychological impact. Our objective was to examine the associations of visual and hearing impairment with subjective well-being (SWB), an important psychological concept defined by life satisfaction [LS], positive affect [PA], negative affect [NA], and affect balance [AB] among long-lived individuals (LLIs) over 95 years of age.', 'Data on 442 LLIs from the Rugao longevity cohort, a population-based study in Rugao, China, were analyzed. Graded classifications of visual and hearing impairment (none, mild, moderate, and severe) were constructed from self-reported items. Bivariate correlation and multiple regression analysis were performed to test the associations.', 'Approximately 66.1% and 87.3% of the subjects reported varying degrees of visual and hearing impairment. Following the degree of vision impairment, LS, PA, and AB decreased linearly, whereas NA increased linearly (all p for trend<0.05). Vision was significantly related to LS (r=0.238, p<0.001), PA (r=0.142, p<0.01), NA (r=-0.157, p<0.001), and AB (r=0.206, p<0.001). After adjustment for multiple variables including functional ability, an important factor of SWB, the associations of vision impairment with LS, NA, and AB, while diminished, still existed.",
            "output": [
                "Is visual impairment , but not hearing impairment , independently associated with lower subjective well-being among individuals over 95 years of age : A population-based study?"
            ]
        },
        {
            "id": "task847-bad1b10f6970471ead07a9d198207f94",
            "input": "Adolescent intermittent alcohol exposure (AIE) has profound effects on neuronal function. We have previously shown that AIE causes aberrant hippocampal structure and function that persists into adulthood. However, the possible contributions of astrocytes and their signaling factors remain largely unexplored. We investigated the acute and enduring effects of AIE on astrocytic reactivity and signaling on synaptic expression in the hippocampus, including the impact of the thrombospondin (TSP) family of astrocyte-secreted synaptogenic factors and their neuronal receptor, alpha2delta-1 (\u03b12\u03b4-1). Our hypothesis is that some of the influences of AIE on neuronal function may be secondary to direct effects on astrocytes.', 'We conducted Western blot analysis on TSPs 1 to 4 and \u03b12\u03b4-1 from whole hippocampal lysates 24 hours after the 4th and 10th doses of AIE, then 24 days after the last dose (in adulthood). We used immunohistochemistry to assess astrocyte reactivity (i.e., morphology) and synaptogenesis (i.e., colocalization of pre- and postsynaptic puncta).', 'Adolescent AIE reduced \u03b12\u03b4-1 expression, and colocalized pre- and postsynaptic puncta after the fourth ethanol (EtOH) dose. By the 10th dose, increased TSP2 levels were accompanied by an increase in colocalized pre- and postsynaptic puncta, while \u03b12\u03b4-1 returned to control levels. Twenty-four days after the last EtOH dose (i.e., adulthood), TSP2, TSP4, and \u03b12\u03b4-1 expression were all elevated. Astrocyte reactivity, indicated by increased astrocytic volume and area, was also observed at that time.",
            "output": [
                "Are adolescent Intermittent Alcohol Exposure : Dysregulation of Thrombospondins and Synapse Formation Associated with Decreased Neuronal Density in the Adult Hippocampus?"
            ]
        },
        {
            "id": "task847-d8d7ec508f444909bfd3243e99fe074c",
            "input": "Obstructive sleep apnea (OSA) is associated with an increased risk of obesity and non-alcoholic fatty liver disease (NAFLD), but it remains unclear whether the risk of NAFLD is independently related to OSA regardless of visceral obesity. Thus, the aim of the present study was to examine whether OSA alone or in combination with excessive daytime sleepiness (EDS) or short sleep duration was associated with NAFLD independent of visceral fat in Korean adults.', 'A total of 621 participants were selected from the Korean Genome and Epidemiology Study (KoGES). The abdominal visceral fat area (VFA) and hepatic fat components of the participants were assessed using computed tomography scans and they were then categorized into four groups depending on the presence of OSA and EDS.', 'The proportions of NAFLD were 21.1%, 18.5%, 32.4%, and 46.7% in participants without OSA/EDS, with only EDS, with only OSA, and with both OSA and EDS, respectively. A combination of OSA and EDS increased the odds ratio (OR) for developing NAFLD (OR, 2.75; 95% confidence interval [CI], 1.21 to 6.28) compared to those without OSA/EDS, and this association remained significant (OR, 2.38; 95% CI, 1.01 to 5.59) even after adjusting for VFA. In short sleepers (< 5 hours) with OSA, the adjusted OR for NAFLD was 2.50 (95% CI, 1.08 to 5.75) compared to those sleeping longer than 5 hours without OSA.",
            "output": [
                "Is obstructive sleep apnea with excessive daytime sleepiness associated with non-alcoholic fatty liver disease regardless of visceral fat?"
            ]
        },
        {
            "id": "task847-504184ac3e8e4588940741bcdc6f624c",
            "input": "The use of tobacco is a well-established cause of preventable morbidity and mortality. There have been few studies examining the effect of tobacco use on outcomes and complications after arthroscopic knee procedures such as anterior cruciate ligament (ACL) reconstruction.', 'To investigate the relationship between tobacco use and rates of postoperative infection, venous thromboembolism (VTE), arthrofibrosis, and subsequent ACL reconstruction after primary ACL reconstruction.', 'Cohort study; Level of evidence, 3.', 'A national insurance database was queried for patients who underwent arthroscopic-assisted ACL reconstruction using Current Procedural Terminology code 29888. Patients underage for tobacco use in all regions of the United States (age <20 years), those with prior ACL reconstruction, and those with the following concomitant procedures were excluded: open cruciate or collateral ligament reconstruction, open or arthroscopic cartilage procedures, patellar stabilization, extra-articular ligamentous reconstruction, and posterior cruciate ligament reconstruction. Tobacco use and non-tobacco use cohorts were queried using International Classification of Diseases-9th Revision coding. The non-tobacco use patients were then matched to the patients with coded tobacco use by age, sex, obesity, diabetes, meniscal repair, and meniscectomy. Complications within 90 days postoperatively were assessed for both cohorts, including infection, VTE, arthrofibrosis, and subsequent ipsilateral or contralateral ACL reconstruction after the index procedure.', 'A total of 13,358 patients who underwent ACL reconstruction met inclusion and exclusion criteria, including 1659 patients with documented tobacco use and 11,699 matched controls. The incidence of infection was significantly higher in patients who use tobacco (2.0%) versus matched controls (0.9%; odds ratio [OR], 2.3; P < .0001). The rate of VTE was also significantly higher in patients who use tobacco (1.0%) compared with matched controls (0.5%; OR, 1.9; P = .035). The rate of subsequent ACL reconstruction was significantly higher in the tobacco use cohort (12.6%) compared with matched controls (7.8%; OR, 1.7; P < .0001). There was no significant difference in the rate of postoperative stiffness after ACL reconstruction between patients who use tobacco (2.0%) and matched controls (2.3%; OR, 0.9; P = .656).",
            "output": [
                "Does tobacco Use be Associated With Increased Complications After Anterior Cruciate Ligament Reconstruction?"
            ]
        },
        {
            "id": "task847-993f1e73454942729c9557f0f871983a",
            "input": "Most human microbiota studies focus on bacteria inhabiting body surfaces, but these surfaces also are home to large populations of viruses. Many are bacteriophages, and their role in driving bacterial diversity is difficult to decipher without the use of in vitro ecosystems that can reproduce human microbial communities.', 'We used chemostat culture systems known to harbor diverse fecal bacteria to decipher whether these cultures also are home to phage communities. We found that there are vast viral communities inhabiting these ecosystems, with estimated concentrations similar to those found in human feces. The viral communities are composed entirely of bacteriophages and likely contain both temperate and lytic phages based on their similarities to other known phages. We examined the cultured phage communities at five separate time points over 24\\xa0days and found that they were highly individual-specific, suggesting that much of the subject-specificity found in human viromes also is captured by this culture-based system. A high proportion of the community membership is conserved over time, but the cultured communities maintain more similarity with other intra-subject cultures than they do to human feces. In four of the five subjects, estimated viral diversity between fecal and cultured communities was highly similar.",
            "output": [
                "Do chemostat culture systems support diverse bacteriophage communities from human feces?"
            ]
        },
        {
            "id": "task847-34dafe983b4649b5b6273c5b8987193e",
            "input": "An increasing number of proteins are being shown to assemble into amyloid structures that lead to pathological states. Among them, mammalian prions outstand due to their ability to transmit the pathogenic conformation, becoming thus infectious. The structural conversion of the cellular prion protein (PrP(C)), into its misfolded pathogenic form (PrP(Sc)) is the central event of prion-driven pathologies. The study of the structural properties of intracellular amyloid aggregates in general and of prion-like ones in particular is a challenging task. In this context, the evidence that the inclusion bodies formed by amyloid proteins in bacteria display amyloid-like structural and functional properties make them a privileged system to model intracellular amyloid aggregation.', 'Here we provide the first demonstration that recombinant murine PrP and its C-terminal domain (90-231) attain amyloid conformations inside bacteria. Moreover, the inclusions formed by these two PrP proteins display conformational diversity, since they differ in fibril morphology, binding affinity to amyloid dyes, stability, resistance to proteinase K digestion and neurotoxicity.",
            "output": [
                "Does mammalian prion protein ( PrP ) form conformationally different amyloid intracellular aggregates in bacteria?"
            ]
        },
        {
            "id": "task847-ad3ee41df1c24dee92f8887bcad5eee7",
            "input": "The B cell leukemia 11A (BCL11A) gene was identified as a proto-oncogene in hematopoietic cell malignancies and breast cancer. Alternative RNA splicing generates three main transcripts designated as Extra-long (XL; 5.9 kb/125 kD), Long (L; 3.8 kb/100 kD) and Short (S; 2.4 kb/35 kD). Our previous study results demonstrated that BCL11A expression levels were specifically upregulated in non-small cell lung cancer (NSCLC) tissues, especially in squamous cell carcinoma (SCC) and large cell carcinoma (LCC).', 'In this study, we detected the BCL11A protein isoforms with immunohistochemistry (IHC) method in NSCLC with in a cohort (n=40) of BCL11A overexpression NSCLC patients. All 40 cases were BCL11A overexpression including 27 SCCs, 8 LCCs and 5 adenocarcinomas (ACs). Relationship between BCL11A isoforms and the clinicopathological parameters were also analyzed.', 'Compare to the BCL11A-L and S isoforms, the BCL11A-XL isoform was specifically expressed in SCC and LCC (P=0.006). There were 19 (19/40, 47.5%) cases positive for BCL11A-XL expression, SCC accounted for 63.2% (12/19) and LCC accounted for 36.8% (7/19). The survival analysis indicated that BCL11A-XL expression was an independent prognostic factor for disease-free survival (DFS) [hazards ratio (HR) 0.246; 95% confidence interval (CI), 0.065-0.939, P=0.040] but not for overall survival (OS) in patients with SCC and LCC.",
            "output": [
                "Does the BCL11A-XL expression predict relapse in squamous cell carcinoma and large cell carcinoma?"
            ]
        },
        {
            "id": "task847-395e12c0658d4b2ca261c13a097563d4",
            "input": "To explore the incidences of chronic obstructive pulmonary disease (COPD), obstructive ventilatory dysfunction, and obstructive small airway disease and their risk factors in a health check-up population, with an attempt to inform the early diagnosis and treatment of COPD.', 'Subjects who aged 20 years and older and received health check-up in the Health Management Center, Third Xiangya Hospital, Central South University from June 2013 to June 2015 were enrolled in this study. The results of detection and survey for COPD, obstructive ventilatory dysfunction, and obstructive small airway disease were analyzed.', 'Among 6,811 subjects enrolled in this study, the detection rate of COPD, obstructive ventilator dysfunction, and obstructive small airway disease was 0.8%, 2.6%, and 4.0%, respectively, which showed a positive correlation with male gender, age, and smoking index.",
            "output": [
                "Does analysis of pulmonary function test result in a health check-up population?"
            ]
        },
        {
            "id": "task847-d51aea98d4174dbca5d62d59886caac1",
            "input": "Tracheo-oesophageal malformations result from disturbed foregut separation during early development. The notochord, a specialised embryonic structure, forms immediately adjacent to the dividing foregut. In the Adriamycin mouse model of oesophageal atresia, foregut and notochord abnormalities co-exist, and the site and severity of foregut malformations closely correlate to the position and extent of the notochord defects. Notochord and foregut abnormalities also co-exist in the Noggin Knockout mouse as well in a small number of human cases. The notochord is a source of powerful molecular signals during early embryogenesis, being particularly important for neural crest development. The influence of notochord signaling on the adjacent foregut is not known. The purpose of this study was to examine the impact of notochord manipulation on foregut separation using a robust 3D explant method for culturing isolated foregut which permits oeosphageal and tracheal formation in vitro.', 'Foregut was micro-dissected from embryonic day 9 mice (License B100/4447 Irish Medicines Board), embedded in collagen and cultured for 48\\xa0h with native notochord intact (n\\xa0=\\xa06), notochord removed (n\\xa0=\\xa010) or additional notochord transplanted from stage matched controls (n\\xa0=\\xa08). Specimens were analysed for foregut morphology and molecular patterning using immunohistochemistry for Hnf3b (an endoderm marker) and Sox2 (a notochord and oesophageal marker) on cryosections.', 'Foregut separation into distinct oesophagus and trachea was observed in isolated foregut specimens with or without their native notochord. In specimens with additional notochord transplants, foregut morphology and molecular patterning were comparable to controls whether or not the native notochord was maintained. In particular foregut separation was not disrupted by the transplantation of additional notochord at the dorsal foregut endoderm.",
            "output": [
                "Does notochord manipulation impact oesophageal and tracheal formation from isolated foregut in 3D explant culture?"
            ]
        },
        {
            "id": "task847-9496d6bbda2549328ab5a346ba01fa5b",
            "input": "We aimed to investigate the anti-angiogenic properties of miR-155 via in vitro and in vivo studies.', 'miR-155 was knocked down using lentivirus-mediated RNA interference. The proliferation, migration, and tube formation of human retinal microvascular endothelial cells (HRMECs) were measured using BrdU, Transwell, and Matrigel assays, respectively. An oxygen-induced retinopathy (OIR) model was induced using neonatal C57BL/6J pups. Anti-miR-155 was intravitreally injected on postnatal day 12, and the retinal non-perfused areas and extent of neovascularization were measured on postnatal day 18 using transcardiovascular fluorescein isothiocyanate (FITC)-dextran perfusion and retina sections. A laser-induced choroidal neovascularization (CNV) model was induced in adult C57BL/6J mice. To evaluate the leakage areas, fundus fluorescein angiography was performed on day 14 after anti-miR-155 intravitreal injection. The neovascularization area of the CNV model was also examined in confocal and retina section studies. The expression levels of SHIP1 and p-Akt (Thr308, Ser473, and Thr450) were evaluated both in vitro and in vivo.', 'The expression of miR-155 was elevated in HRMECs after treatment with vascular endothelial growth factor (VEGF) and in neovascularized mouse model retinas. Anti-miR-155 lentivirus reduced the VEGF-induced proliferation, migration, and tube formation abilities of HRMECs. Anti-miR-155 attenuated retinal neovascularization in in vivo CNV and OIR models. In VEGF-treated HRMECs and retina neovascularization models, p-Akt (Ser473) was significantly upregulated, while SHIP1 was downregulated. Conversely, the inhibition of miR-155 restored the expression of SHIP1 and reduced the phosphorylation of effectors in the Akt (Ser473) signaling pathway.",
            "output": [
                "Does down-regulation of microRNA-155 attenuate retinal neovascularization via the PI3K/Akt pathway?"
            ]
        },
        {
            "id": "task847-2da7064113c04e6295165d8ee48b7c01",
            "input": "Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other.', 'Ovalbumin sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth muscle cell loss, cell proliferation, and angiogenesis in AAA lesions. ALI also increased plasma IgE, reduced plasma interleukin-5, and increased bronchioalveolar total inflammatory cell and eosinophil accumulation. Intraperitoneal administration of an anti-IgE antibody suppressed AAA lesion formation and reduced lesion inflammation, plasma IgE, and bronchioalveolar inflammation. Pre-establishment of ALI also increased AAA lesion size, lesion accumulation of macrophages and mast cells, media smooth muscle cell loss, and plasma IgE, reduced plasma interleukin-5, interleukin-13, and transforming growth factor-\u03b2, and increased bronchioalveolar inflammation. Consequent production of ALI also doubled lesion size of pre-established AAA and increased lesion mast cell and T-cell accumulation, media smooth muscle cell loss, lesion cell proliferation and apoptosis, plasma IgE, and bronchioalveolar inflammation. In periaortic CaCl2 injury-induced AAA in mice, production of ALI also increased AAA formation, lesion inflammation, plasma IgE, and bronchioalveolar inflammatory cell accumulation.",
            "output": [
                "Does allergic Lung Inflammation aggravate Angiotensin II-Induced Abdominal Aortic Aneurysms in Mice?"
            ]
        },
        {
            "id": "task847-5d7d9999e8064837a2dd0868fc3d15e0",
            "input": "Radical surgical resection of cerebral meningiomas involving the dura mater of venous sinuses is challenging, and tumor residuals are frequently left after surgery. This study sought to evaluate the effect of adjuvant stereotactic radiosurgery (aSRS) on the time to significant growth of meningioma residuals requiring retreatment.', 'A total of 119 consecutive patients (2004-2013) receiving primary surgical treatment for a meningioma in proximity to a venous structure were included. The patients were assessed retrospectively, with a focus on retreatments and mortality. Radicality of initial tumor surgery was scored using postoperative magnetic resonance imaging. Three subgroups were identified: 1) radical total resection (RTR); 2) near-total resection (NTR), followed by aSRS (NTR\\xa0+ aSRS); and 3) NTR but no aSRS (NTR\\xa0- aSRS). In the NTR\\xa0- aSRS group, intervention was initiated after radiologic (magnetic resonance imaging) findings verified growth of residual tumor, in contrast to the NTR\\xa0+ aSRS group, which received aSRS before regrowth. Time to first retreatment, progression-free survival (PFS), and overall survival were analyzed with the log-rank test and multiple-events Cox regression.', 'RTR was associated with the best prognosis. The patients in the NTR\\xa0+ aSRS group had significantly longer time to first retreatment compared with NTR\\xa0- aSRS patients (P < 0.001). There was also a significant difference in mortality (P < 0.05) and a tendency to prolonged PFS (P\\xa0=\\xa00.07) in the NTR\\xa0+ aSRS group. The Cox regressions confirmed the positive effects of NTR\\xa0+ aSRS on time to retreatment (hazard ratio, 7.3; P < 0.01) and PFS (hazard ratio, 3.69; P\\xa0= 0.055).",
            "output": [
                "Does adjuvant Stereotactic Radiosurgery reduce Need for Retreatments in Patients with Meningioma Residuals?"
            ]
        },
        {
            "id": "task847-0f21ace63cdf4a04a5523a0c7a05da54",
            "input": "Imitation, which is impaired in children with autism spectrum disorder (ASD) and critically depends on the integration of visual input with motor output, likely impacts both motor and social skill acquisition in children with ASD; however, it is unclear what brain mechanisms contribute to this impairment. Children with ASD also exhibit what appears to be an ASD-specific bias against using visual feedback during motor learning. Does the temporal congruity of intrinsic activity, or functional connectivity, between motor and visual brain regions contribute to ASD-associated deficits in imitation, motor, and social skills?', 'We acquired resting-state functional magnetic resonance imaging scans from 100 8- to 12-year-old children (50 ASD). Group independent component analysis was used to estimate functional connectivity between visual and motor systems. Brain-behavior relationships were assessed by regressing functional connectivity measures with social deficit severity, imitation, and gesture performance scores.', 'We observed increased intrinsic asynchrony between visual and motor systems in children with ASD and replicated this finding in an independent sample from the Autism Brain Imaging Data Exchange. Moreover, children with more out-of-sync intrinsic visual-motor activity displayed more severe autistic traits, while children with greater intrinsic visual-motor synchrony were better imitators.",
            "output": [
                "Does intrinsic Visual-Motor Synchrony correlate With Social Deficits in Autism?"
            ]
        },
        {
            "id": "task847-90e3b7f87ffd43eb95229f5e32559df2",
            "input": "Erectile dysfunction (ED) and cardiovascular disease (CVD) share a great number of common risk factors. There is growing evidence that aldosterone, an independent CVD risk factor, is associated with ED.', 'The purpose of this study was to determine the relationship between plasma aldosterone and erectile dysfunction.', 'This study recruited 287 participants, ranging from 18 to 84\\xa0years old; 217 were suffering from ED, diagnosed by the International Index of Erectile Function 5 (IIEF-5) scores. Based on IIEF-5 scores, patients were divided into one control group and three ED groups (mild ED; moderate ED; severe ED).', 'The differences in principal characteristics, blood routine, sexual hormone, adrenal hormone, thyroid hormone, renal function, liver function and blood lipid were compared between ED and control groups.', 'Our study demonstrated that the difference of mean plasma aldosterone levels between ED group and the control group was statistically significant (P\\xa0<\\xa00.05). Stepwise logistic regression analysis of all the possible factors support the role of aldosterone as an independent risk factor for ED (OR 1.011; 95\\xa0% CI 1.003-1.018; P\\xa0=\\xa00.004). Similar statistical methods were applied to the comparison between moderate to severe ED group and control to mild ED group (OR 1.017; 95\\xa0% CI 1.009-1.024; P\\xa0<\\xa00.001). ROC curve and the area under the curve (0.718; 95\\xa0% CI 0.643-0.794; P\\xa0<\\xa00.001) were performed to assess the diagnostic effect and to compare the severity of risk with the known independent risk factors, such as age and cholesterol (0.704; 95\\xa0% CI 0.631-0.778; P\\xa0<\\xa00.001). When using a 374\\xa0pg/mL cut-off value from Youden index, the OR of ED group versus controls is 3.106 (95\\xa0% CI 1.458-6.617), while the OR of moderate to severe ED versus control and mild ED is 5.480 (95\\xa0% CI 3.108-9.662).",
            "output": [
                "Is elevated plasma aldosterone an independent risk factor for erectile dysfunction in men?"
            ]
        },
        {
            "id": "task847-739c0eea2e4540deb70618c8feaafa7c",
            "input": "To compensate for the lack of haptic feedback by surgical robots, limitation of exerted forces could be implemented. The limits should be based on the observed relationship between tissue load and induced damage. This study examines whether age-related changes influence this relationship.', 'Descending thoracic aortas of male C57BL/6J mice of 10, 25 and 40 weeks were clamped in vivo (no clamp, 0.5N or 2.0N) for 2 min. Functional integrity was tested in vitro by studying endothelium-dependent and -independent vasoreactivity.', 'Endothelium-dependent relaxation deteriorated with increased clamping force at all ages. Clamping did not influence endothelium-independent vasodilation. Age (10, 25 and 40 weeks) did not significantly impact on the effect of clamping on endothelium-dependent and independent vasoreactivity.",
            "output": [
                "Is arterial Vasoreactivity Equally Affected by In Vivo Cross-Clamping with Increasing Loads in Young and Middle-Aged Mice Aortas?"
            ]
        },
        {
            "id": "task847-914320503cb142c8aa1e59041fbe38bc",
            "input": "Under conditions of inflammation in the absence of micro-organisms (sterile inflammation), necrotic cells release damage-associated molecular patterns that bind to Toll-like receptors on immune cells to activate a signaling pathway that involves activation of I\u03baB kinase and nuclear factor \u03baB (NF-\u03baB). Little is known about the mechanisms that control NF-\u03baB activity during sterile inflammation. We analyzed the contribution of B-cell CLL/lymphoma 3 (BCL3), a transcription factor that associates with NF-\u03baB, in control of sterile inflammation in the pancreas and biliary system of mice.', 'Acute pancreatitis (AP) was induced in C57BL/6 (control) and Bcl3(-/-) mice by intraperitoneal injection of cerulein or pancreatic infusion of sodium taurocholate. We also studied Mdr2(-/-) mice, which develop spontaneous biliary inflammation, as well as Bcl3(-/-)Mdr2(-/-) mice. We performed immunohistochemical analyses of inflamed and noninflamed regions of pancreatic tissue from patients with AP or primary sclerosing cholangitis (PSC), as well as from mice. Immune cells were characterized by fluorescence-activated cell sorting analysis. Control or Bcl3(-/-) mice were irradiated, injected with bone marrow from Bcl3(-/-) or control mice, and AP was induced.', 'Pancreatic or biliary tissues from patients with AP or PSC had higher levels of BCL3 and phosphorylated RelA and I\u03baB\u03b1 in inflamed vs noninflamed regions. Levels of BCL3 were higher in pancreata from control mice given cerulein than from mice without AP, and were higher in biliary tissues from Mdr2(-/-) mice than from control mice. Bcl3(-/-) mice developed more severe AP after administration of cerulein or sodium taurocholate than control mice; pancreata from the Bcl3(-/-) mice with AP had greater numbers of macrophages, myeloid-derived suppressor cells, dendritic cells, and granulocytes than control mice with AP. Activation of NF-\u03baB was significantly prolonged in Bcl3(-/-) mice with AP, compared with control mice with AP. Bcl3(-/-)Mdr2(-/-) mice developed more severe cholestasis and had increased markers of liver injury and increased proliferation of biliary epithelial cells and hepatocytes than Mdr2(-/-) mice. In experiments with bone marrow chimeras, expression of BCL3 by acinar cells, but not myeloid cells, was required for reduction of inflammation\\xa0during development of AP. BCL3 inhibited ubiquitination and proteasome-mediated degradation of p50 homodimers, which prolonged binding of NF-\u03baB heterodimers to DNA.",
            "output": [
                "Does bCL3 reduce the Sterile Inflammatory Response in Pancreatic and Biliary Tissues?"
            ]
        },
        {
            "id": "task847-5f1a2e6f8f074acebd7b4dbc01a1dd67",
            "input": "To determine the association between regular Chinese green tea consumption and the risk of diabetic retinopathy (DR) in diabetic patients in China.', '100 DR patients and 100 age-sex-matched diabetic controls without retinopathy were recruited in a clinic-based, case-control study. DR was defined from retinal photographs and detailed information on Chinese green tea consumption of the participants was collected through a face-to-face interview.', 'The crude odds ratio [OR] of Chinese green tea consumption for DR was 0.49 (95% confidence interval: 0.26-0.90). When stratified by sex, the protective effect of Chinese green tea consumption on DR was statistically significant in women (P = 0.01) but not in men (P = 0.63). After adjusting for age, sex, and other confounders, DR was significantly associated with Chinese green tea consumption (OR = 0.48; P = 0.04), higher systolic blood pressure (OR = 1.02; P = 0.05), longer duration of diabetes (OR = 1.07; P = 0.02), and the presence of family history of diabetes (OR = 2.35; P = 0.04).",
            "output": [
                "Is regular Chinese Green Tea Consumption Protective for Diabetic Retinopathy : A Clinic-Based Case-Control Study?"
            ]
        },
        {
            "id": "task847-6a97ca633e914857ab7c50804aa2f36a",
            "input": "Chagas heart disease (CHD) patients may have a reduced functional capacity (FC). Field tests, as the Incremental Shuttle Walk Test (ISWT), can estimate peak oxygen uptake (VO2 peak). However, the relationship between the ISWT and the Cardiopulmonary Exercise Testing (CPET), the gold standard in the assessment of FC, is not well established in CHD patients.', 'This study aimed to evaluate the FC of CHD patients by ISWT with direct measurement of VO2 peak and to compare these findings with data obtained from CPET. A secondary goal was to derive a regression equation to calculate the VO2 peak by ISWT.', 'Cross-sectional and correlative study.', 'Research laboratory setting.', 'Thirty-two CHD patients (58.8\u00b19.0 years, 81.3% women) participated in this study.', 'Eligible patients underwent clinical evaluation, echocardiography, CPET by ramp protocol and ISWT according to current guidelines.', 'The distance walked in ISWT showed a positive correlation with VO2 peak from CPET and ISWT (r=0.456, P=0.009 and r=0.869, P<0.001, respectively). In the agreement analysis, the values of the differences between VO2 peak from CPET and ISWT showed absence of bias (mean bias \u00b195% CI and mean -1.29\u00b15.09 mL.kg.min). Based in real values of VO2 obtained from ISWT, one equation including sex, functional class and distance walked was provided to predict the VO2 values in this test.",
            "output": [
                "Do peak oxygen uptake during the incremental shuttle walk test in a predominantly female population with Chagas heart disease?"
            ]
        },
        {
            "id": "task847-52ae3b0fc6e04762a7cad2eaca035a4d",
            "input": "Posttraumatic stress symptoms are common after intensive care treatment. The influence of anxiety during critical illness on the development of posttraumatic stress symptoms needs to be investigated.', 'To determine the association between anxiety during critical illness (state and trait components) and posttraumatic stress symptoms over six months after ICU discharge.', 'Prospective study including 141 patients admitted \u226524h to a closed mixed adult ICU in a tertiary hospital. State anxiety was assessed with the Faces Anxiety Scale during ICU stay. Trait anxiety was measured with the State-Trait Anxiety Inventory Form Y-2. Posttraumatic stress symptoms were measured at three and six months after ICU discharge using the Post-Traumatic Stress Symptoms 10-Question Inventory. Clinical and demographical data were also collected. Mixed effect regression models were used to determine if state and trait anxiety were factors significantly associated with posttraumatic stress symptoms over time.', 'Moderate to severe levels of state anxiety in ICU were reported by 81 (57%) participants. Levels of trait anxiety (median 36 IQR: 29-47) were similar to the Australian population. High levels of posttraumatic stress symptoms occurred at three (n=19, 19%) and six months (n=15, 17%). Factors independently associated with posttraumatic stress symptoms were trait anxiety (2.2; 95% CI, 0.3-4.1; p=0.02), symptoms of anxiety after ICU discharge (0.6; 95% CI, 0.2-1.1; p=0.005), younger age (-1.4; 95% CI, -2.6 to -0.2; p=0.02) and evidence of mental health treatment prior to the ICU admission (5.2; 95% CI, 1.5-8.9; p=0.006).",
            "output": [
                "Is in ICU state anxiety associated with posttraumatic stress symptoms over six months after ICU discharge : A prospective study?"
            ]
        },
        {
            "id": "task847-2f7674a8161c4279952bd5ff0c1c1516",
            "input": "Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role.', 'Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin.', 'Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2\u00d710",
            "output": [
                "Does dense genotyping of immune-related loci identify HLA variants associated with increased risk of collagenous colitis?"
            ]
        },
        {
            "id": "task847-3507e25d488b41258acff820ad03ff2c",
            "input": "Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules.', 'The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution.', 'Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-\u03b1 levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments.', 'Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175\u00b117 nm and span of 1.6\u00b10.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-\u03b1 (P=0.001) and IL-1\u03b1 (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX.",
            "output": [
                "Are methotrexate-loaded lipid-core nanocapsules highly effective in the control of inflammation in synovial cells and a chronic arthritis model?"
            ]
        },
        {
            "id": "task847-a22cdf363d9b412188b4196086a4a179",
            "input": "The microcirculation supplies oxygen (O2) and nutrients to all cells with the red blood cell (RBC) acting as both a deliverer and sensor of O2. In sepsis, a proinflammatory disease with microvascular complications, small blood vessel alterations are associated with multi-organ dysfunction and poor septic patient outcome. We hypothesized that microvascular autoregulation-existing at three levels: over the entire capillary network, within a capillary and within the erythrocyte-was impaired during onset of sepsis. This study had three objectives: 1) measure capillary response time within hypoxic capillaries, 2) test the null hypothesis that RBC O2-dependent adenosine triphosphate (ATP) efflux was not altered by sepsis and 3) develop a framework of a pathophysiological model.', 'This was an animal study, comparing sepsis with control, set in a university laboratory. Acute hypotensive sepsis was studied using cecal ligation and perforation (CLP) with a 6-hour end-point. Rat hindlimb skeletal muscle microcirculation was imaged, and capillary RBC supply rate (SR\\u2009=\\u2009RBC/s), RBC hemoglobin O2 saturation (SO2) and O2 supply rate (qO2\\u2009=\\u2009pLO2/s) were quantified. Arterial NOx (nitrite\\u2009+\\u2009nitrate) and RBC O2-dependent ATP efflux were measured using a nitric oxide (NO) analyzer and gas exchanger, respectively.', \"Sepsis increased capillary stopped-flow (p\\u2009=\\u20090.001) and increased plasma lactate (p\\u2009<\\u20090.001). Increased plasma NOx (p\\u2009<\\u20090.001) was related to increased capillary RBC supply rate (p\\u2009=\\u20090.027). Analysis of 30-second SR-SO2-qO2 profiles revealed a shift towards decreased (p\\u2009<\\u20090.05) O2 supply rates in some capillaries. Moreover, we detected a three- to fourfold increase (p\\u2009<\\u20090.05) in capillary response time within hypoxic capillaries (capillary flow states where RBC SO2\\u2009<\\u200920\\xa0%). Additionally, sepsis decreased the erythrocyte's ability to respond to hypoxic environments, as normalized RBC O2-dependent ATP efflux decreased by 62.5\\xa0% (p\\u2009<\\u20090.001).",
            "output": [
                "Does sepsis impair microvascular autoregulation and delays capillary response within hypoxic capillaries?"
            ]
        },
        {
            "id": "task847-72b2a37f6d86476d9f4c4c5e4212da6e",
            "input": "Normal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance.', 'Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metabolism was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist.', 'Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass.",
            "output": [
                "Does acute disruption of glucagon secretion or action improve glucose tolerance in an insulin-deficient mouse model of diabetes?"
            ]
        },
        {
            "id": "task847-1fe598318ef545a1a8dfcf0d001395ac",
            "input": "The Wada test is a diagnostic method to anesthetize 1 cerebral hemisphere and assess the language and memory functions of awake contralateral hemisphere before temporal lobectomy in patients with epilepsy. The effects of an ipsilateral injection of etomidate on the functional properties of contralateral hemisphere are not known. Our aim was to characterize the electroencephalographic (EEG) effects after intracarotid injection of etomidate and to determine the changes in synchronization between the ipsilateral and contralateral hemispheres.', 'We retrospectively analyzed EEG data from 15 patients who underwent Wada test with etomidate. Continuous EEG data from 4 electrodes (2 anterior [F3, F4] and 2 posterior [P3, P4]) were analyzed. After artifact rejection, we measured the amplitudes of delta (1 to 4 Hz) and alpha (7 to 13 Hz) waves and the changes in the interhemispheric synchronization before, during, and after etomidate injection.', 'Ipsilateral injection of etomidate causes EEG changes in both hemispheres with increased amplitude of delta waves anteriorly and the alpha waves posteriorly. However this effect of etomidate is not uniform. Although there was a decrease in the interhemispheric synchronization of delta waves, there was no change in the synchronization of the alpha waves.",
            "output": [
                "Does intracarotid Etomidate decrease the Interhemispheric Synchronization in Electroencephalogram ( EEG ) During the Wada Test?"
            ]
        },
        {
            "id": "task847-b7757ad525f44ecc9a30260ca4e37755",
            "input": "In the present study, we made an attempt to elucidate the role of oversecretion of interleukin-4 (IL-4) in cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC).', 'HNSCC samples were analyzed for the presence of CSCs by flow cytometry. In addition, we have performed drug and apoptosis resistance assays to determine the role of IL-4 in CSCs.', 'HNSCC samples contained 3.3% of CD133+ cancer stem like side population (SP) cells in HNSCC which displayed infinite cell proliferation and they had high self-renewal capacity. These CD133+ cells displayed enhanced expression of IL-4, which promoted multidrug and apoptosis resistance. After neutralizing IL-4, the CD133+ SP cells became more sensitive to drug treatment and apoptosis.",
            "output": [
                "Does constitutive secretion of Interleukin-4 dictate CD133+ side population cells to resist drug treatment and cell death?"
            ]
        },
        {
            "id": "task847-8c01a12537b74a88b4efe3c1a69d2c8c",
            "input": "To explore the antitumor effect of prescription consisting of Vitamin C (Vc) and Baicalin (PVB).', 'To explore the antitumor effect of PVB, using U14 cervical tumor-bearing mice model was used and the drugs were administrated through the gavages. Spectrophotometry was used to determine the content of superoxide dismutase (SOD), malondialdehyde (MDA) and cytokines IL-2, Il-4 and IFN-\u03b3.', 'PVB had a better antitumor effect than baicalin and Vc used alone with an inhibition rate of 58.18% (p<0.05); PVB significantly improved the spleen index (p<0.01), and significantly reduced MDA content (p<0.01) but increased SOD activity in liver tissue and serum (p<0.01).",
            "output": [
                "Does prescription consisting of Vitamin C and Baicalin inhibit tumor growth by enhancing the antioxidant capacity in vivo?"
            ]
        },
        {
            "id": "task847-e41741cfe91a456cb0e7f2d7410ce1b0",
            "input": "There is debate surrounding the use of laparoscopic resection for advanced gastric cancer in the Western population. Here we aim to assess the feasibility and short-term outcomes of laparoscopic gastrectomy in consecutive patients in a Western population.', 'From 2012 to 2014, retrospective review of 28 patients with clinically staged advanced gastric cancer (\u2265T3 or \u2265N1) treated with laparoscopic resection.', 'Sixty-one percentage of patients were male. Median age was 67 years (range 35-86). Median BMI was 26.5 (range 19.4-46.1). Resection types were proximal (n\\xa0=\\xa02), distal (n\\xa0=\\xa014), and total (n\\xa0=\\xa012). Twenty-six (93\\xa0%) patients underwent D2 lymphadenectomy. Four patients underwent conversion to open. Median blood loss was 125\\xa0mL (range 30-300). Median LOS was 7\\xa0days (range 4-16). Of postoperative complications, five were minor: arrhythmia (n\\xa0=\\xa01), surgical site infection (n\\xa0=\\xa03), in-hospital fall (n\\xa0=\\xa01); and four were major (intra-abdominal abscess, stricture, PE, and anastomotic bleed). T stages were Tx (n\\xa0=\\xa01), T2 (n\\xa0=\\xa03), T3 (n\\xa0=\\xa018), and T4 (n\\xa0=\\xa06). N stages were N0 (n\\xa0=\\xa04), N1 (n\\xa0=\\xa08), N2 (n\\xa0=\\xa01), and N3 (n\\xa0=\\xa015). Median tumor size was 5.8\\xa0cm (range 0-9.5). Median lymph node yield was 22 (range 6-53). All margins were negative. Median follow-up was 12.8\\xa0months (range 2-27). Six patients have died of progressive disease.",
            "output": [
                "Is total laparoscopic resection for advanced gastric cancer safe and feasible in the Western population?"
            ]
        },
        {
            "id": "task847-36e5d6cb4c8045a1b0767aa825e36dbd",
            "input": "We have previously shown that endogenously active purinergic P2X7 receptors (P2X7Rs) in satellite glial cells of dorsal root ganglia (DRGs) stimulate ATP release. The ATP activates P2Y1Rs located in the enwrapped neuronal somata, resulting in down-regulation of P2X3Rs. This P2X7R-P2Y1-P2X3R inhibitory control significantly reduces P2X3R-mediated nociceptive responses. The underlying mechanism by which the activation of P2Y1Rs inhibits the expression of P2X3Rs remains unexplored.', 'Examining the effect of the activation of p38 mitogen-activated protein kinase on the expression of P2X3Rs in DRGs, we found that the p38 activator, anisomycin (Anis), reduced the expression of P2X3Rs. Blocking the activity of SGCs by the glial Krebs cycle inhibitor, fluorocitrate, did not change the effect of Anis. These results suggest that neuronal p38 plays a major role in the inhibition of P2X3R expression. Western blotting analyses showed that inhibiting P2Y1Rs by MRS2179 (MRS) or blocking P2X7Rs by either oxATP or A740003 reduced pp38 and increased P2X3R expression in DRGs. These results are further supported by the immunohistochemical study showing that P2X7R and P2Y1R antagonists reduce the percentage of pp38-positive neurons. These observations suggest that activation of P2X7Rs and P2Y1Rs promotes p38 activity to exert inhibitory control on P2X3R expression. Since activation of p38 by Anis in the presence of either A740003 or MRS could overcome the block of P2X7R-P2Y1R inhibitory control, p38 in DRG neurons is downstream of P2Y1Rs. In addition, inhibition of p38 by SB202190 was found to prevent the P2X7R and P2Y1R block of P2X3R expression and increase P2X3R-mediated nociceptive flinch behaviors.",
            "output": [
                "Does p38 MAPK mediate glial P2X7R-neuronal P2Y1R inhibitory control of P2X3R expression in dorsal root ganglion neurons?"
            ]
        },
        {
            "id": "task847-ea8d49482e1844cd83580d7b1089a317",
            "input": "TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49).', 'We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events.",
            "output": [
                "Do tECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability?"
            ]
        },
        {
            "id": "task847-984e4ed10cb84ee3ad2dbf6dd099b17c",
            "input": "Increasing evidence is demonstrating that infants born early on during the term period are at increased risk of morbidity compared with infants born closer to a complete 40 week gestational pregnancy. The purpose of this study was to compare early term [gestation age (GA): 37-37 6/7 weeks] neonatal outcomes with those of other full term neonatal intensive care unit (NICU) admissions.', 'Retrospective chart review of all term infants admitted to the NICU at New York University Langone Medical Center over a 17 month period. Subjects were grouped and analyzed according to their GA at birth: 1) early term infants (GA between 37 0/7 to 37 6/7 weeks) and 2) other term infants (38 0/7 weeks and older).', 'Early term infants were more likely to require NICU care than other term infants [relative risk: 1.42, 95% confidence interval (CI)=1.07-1.88), P=0.01]. In the NICU, they are more likely to manifest respiratory distress syndrome [odds ratio (OR)=5.7, 95% CI=1.6-19.8, P<0.01] and hypoglycemia (OR=4.6, 95% CI=2.0-10.4, P<0.001). In addition, early term neonates were more likely to be born via elective cesarean section than other term neonates (OR=4.1, 95% CI=2.0-8.5, P<0.001).",
            "output": [
                "Are early term infants at increased risk of requiring neonatal intensive care?"
            ]
        },
        {
            "id": "task847-761afcc07c9d4a01b6c6e70336525952",
            "input": "Chronic opioid therapy for chronic pain treatment has increased. Hospital physicians, including hospitalists and medical/surgical resident physicians, care for many hospitalized patients, yet little is known about opioid prescribing at hospital discharge and future chronic opioid use.', \"We aimed to characterize opioid prescribing at hospital discharge among 'opioid na\u00efve' patients. Opioid na\u00efve patients had not filled an opioid prescription at an affiliated pharmacy 1 year preceding their hospital discharge. We also set out to quantify the risk of chronic opioid use and opioid refills 1 year post discharge among opioid na\u00efve patients with and without opioid receipt at discharge.\", 'This was a retrospective cohort study.', 'From 1 January 2011 to 31 December 2011, 6,689 opioid na\u00efve patients were discharged from a safety-net hospital.', 'Chronic opioid use 1 year post discharge.', 'Twenty-five percent of opioid na\u00efve patients (n\\u2009=\\u20091,688) had opioid receipt within 72 hours of discharge. Patients with opioid receipt were more likely to have diagnoses including neoplasm (6.3% versus 3.5%, p\\u2009<\\u20090.001), acute pain (2.7% versus 1.0 %, p\\u2009<\\u20090.001), chronic pain at admission (12.1% versus 3.3%, p\\u2009<\\u20090.001) or surgery during their hospitalization (65.1% versus 18.4%, p\\u2009<\\u20090.001) compared to patients without opioid receipt. Patients with opioid receipt were less likely to have alcohol use disorders (15.7% versus 20.7%, p\\u2009<\\u20090.001) and mental health disorders (23.9% versus 31.4%, p\\u2009<\\u20090.001) compared to patients without opioid receipt. Chronic opioid use 1 year post discharge was more common among patients with opioid receipt (4.1% versus 1.3%, p\\u2009<\\u20090.0001) compared to patients without opioid receipt. Opioid receipt was associated with increased odds of chronic opioid use (AOR\\u2009=\\u20094.90, 95% CI 3.22-7.45) and greater subsequent opioid refills (AOR\\u2009=\\u20092.67, 95% CI 2.29-3.13) 1 year post discharge compared to no opioid receipt.",
            "output": [
                "Does opioid Prescribing at Hospital Discharge contribute to Chronic Opioid Use?"
            ]
        },
        {
            "id": "task847-f30a10f9f59c4d3b9f652614c5a70a64",
            "input": "Children with intussusception require rapid and accurate diagnosis to enable timely intervention for satisfactory outcome. Ultrasonography is the recommended standard diagnostic modality; however, abdominal radiography (AR) is still used as an initial investigation. The aim of this study was to investigate the benefit of AR in intussusception by determining diagnostic accuracy and analysing correlation of AR findings with outcome.', 'Index cases of intussusception presenting over 15\\xa0years (1998-2013) were analysed. Those who had AR performed were allocated into groups with positive or normal findings. Outcome of pneumatic reduction of intussusception (PRI) between these groups was compared.', 'Six hundred and forty-four cases of intussusception treated with PRI were identified, 412 (64\\xa0%) had AR performed and 232 (36\\xa0%) did not. 303 (74\\xa0%) radiographs had positive findings and 109 (26\\xa0%) were normal. The success rate of PRI did not differ between AR positive (82\\xa0%) and AR normal (84\\xa0%). Occult pneumoperitoneum was not detected in any patient by AR in our cohort.",
            "output": [
                "Is abdominal radiography necessary in children with intussusception?"
            ]
        },
        {
            "id": "task847-23d298b5e4374869bb76de321196e6fd",
            "input": "If patients with idiopathic normal pressure hydrocephalus (INPH) also have depression, this could have important clinical ramifications in assessment and management of their cognitive function and response to shunting. In many dementias, depression is overrepresented, but the prevalence of depression in shunted patients with INPH is unknown.', 'The objective of this case-control study was to assess the prevalence of symptoms of depression in shunted INPH patients compared with population-based controls.', 'INPH patients consecutively shunted from 2008 to 2010 in Sweden were analyzed. Patients remaining after inclusion (within 60-85 years and not having dementia, ie, mini-mental state examination \u226523) had a standardized visit to their healthcare provider and answered an extensive questionnaire. Age- and sex-matched population-based controls underwent the same procedure. Symptoms of depression were assessed using the Geriatric Depression Scale 15 (suspected depression defined as \u22655 points, suspected severe depression as \u226512 points). This study is part of the INPH-CRasH study.', 'One hundred seventy-six INPH patients and 368 controls participated. After adjustment for age, sex, cerebrovascular disease, and systolic and diastolic blood pressure, patients had a higher mean depression score (patients: 4.9 \u00b1 3.7 SD, controls: 1.9 \u00b1 2.3 SD; OR 1.4, 95% CI 1.3-1.6, P < .001), more patients had suspected depression (46% vs 13%, OR 6.4, 95% CI 3.8-10.9, P < .001), and more patients had suspected severe depression (7.3% vs 0.6%, OR 14.4, 95% CI 3.0-68.6, P < .005).",
            "output": [
                "Are symptoms of Depression Common in Patients With Idiopathic Normal Pressure Hydrocephalus : The INPH-CRasH Study?"
            ]
        },
        {
            "id": "task847-e260ad12a9664410a67cf11bded4a504",
            "input": "Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression.', 'Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured.', 'Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0%\\xa0\u00b1\\xa013.6 increase compared to 57.8%\\xa0\u00b1\\xa06.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5\\xa0kPa\\xa0\u00b1\\xa093.6 versus 621.4\\xa0kPa\\xa0\u00b1\\xa084.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size.",
            "output": [
                "Do background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility?"
            ]
        },
        {
            "id": "task847-dec30c3395314652bd9f6cf9d7b90d94",
            "input": "Fruiting body lectins have been proposed to act as effector proteins in the defense of fungi against parasites and predators. The Marasmius oreades agglutinin (MOA) is a lectin from the fairy ring mushroom with specificity for Gal\u03b11-3Gal containing carbohydrates. This lectin is composed of an N-terminal carbohydrate-binding domain and a C-terminal dimerization domain. The dimerization domain of MOA shows in addition calcium-dependent cysteine protease activity, similar to the calpain family.', 'Cell detachment assay, cell viability assay, immunofluorescence, live cell imaging and Western blot using MDCKII cell line.', 'In this study, we demonstrate in MDCKII cells that after internalization, MOA protease activity induces profound physiological cellular responses, like cytoskeleton rearrangement, cell detachment and cell death. These changes are preceded by a decrease in FAK phosphorylation and an internalization and degradation of \u03b21-integrin, consistent with a disruption of integrin-dependent cell adhesion signaling. Once internalized, MOA accumulates in late endosomal compartments.",
            "output": [
                "Does uptake of Marasmius oreades agglutinin disrupt integrin-dependent cell adhesion?"
            ]
        },
        {
            "id": "task847-2ab108d6f745419884379fae8796755b",
            "input": "CD73 is a membrane associated 5'-ectonucleotidase that has been proposed as prognostic biomarker in various solid tumors. The aim of this study is to evaluate CD73 expression in a cohort of patients with primary bladder cancer in regard to its association with clinicopathological features and disease course.\", 'Tissue samples from 174 patients with a primary urothelial carcinoma were immunohistochemically assessed on a tissue microarray. Associations between CD73 expression and retrospectively obtained clinicopathological data were evaluated by contingency analysis. Survival analysis was performed to investigate the predictive value of CD73 within the subgroup of pTa and pT1 tumors in regard to progression-free survival (PFS).', 'High CD73 expression was found in 46 (26.4%) patients and was significantly associated with lower stage, lower grade, less adjacent carcinoma in situ and with lower Ki-67 proliferation index. High CD73 immunoreactivity in the subgroup of pTa and pT1 tumors (n = 158) was significantly associated with longer PFS (HR: 0.228; p = 0.047) in univariable Cox regression analysis.",
            "output": [
                "Does cD73 predict Favorable Prognosis in Patients with Nonmuscle-Invasive Urothelial Bladder Cancer?"
            ]
        },
        {
            "id": "task847-7aa7bb1a5d5543bb869ad90e62e95e1d",
            "input": "Nerve growth factor (NGF) is a neurotrophin which promotes and regulates the survival of neurons in the peripheral nervous system. The aim of this study was to investigate the effect of high-pressure administration of sterile physiological saline isotonic solution (HpPSIS) into nasal cavity of laboratory animals on NGF levels and NGF-receptor expression in the olfactory bulbs and brain.', \"For this study we used three weeks old female Sprague Dawley SD rats (n=48). Rats were divided into two groups, the first one treated delivering physiological saline solution with a normal syringe modified at the extremity to fit the rats' nostril (5 ml) (n=24) and the second one treated spray with HpPSIS (n=24 rats). Rats were treated three times a day either for 5 consecutive days (shorth term treatment) or 10 consecutive days (longer treatment) in both nostrils of HpPSIS delivered at high pressure (pression emission level: PEL: 7 g/sec for emission time ET: 0.5 sec) with a specific forced spray erogator. Untreated rats received a similar manipulation three times a day through a syringe in the nostrils, but no HpPSIS administration.\", 'The results of these studies highlight the possibility that endogenous enhancement of NGF by stimulation of NGF-producing cells within the nasal cavities and also in the CNS represent a novel experimental approach to enhance the brain NGF levels with a new therapy. HpPSIS treatment further enhances the presence of NGF in the four brains examined. Indeed, a significant increase of NGF was first observed after 5 days of HpPSIS treatment, compared to HpPSIS untreated rats. The increase was over 25% in the OB, ST, HI and in CX, while 10 days after HpPSIS treatments the levels of NGF were even higher. These differences were statistically significant, p < 0.05.",
            "output": [
                "Does high-pressure physiological saline isotonic solution administration enhance brain NGF and NGF-receptors expression?"
            ]
        },
        {
            "id": "task847-68a0fd4e097f4bba8d9392e113d4c4f5",
            "input": "Pooled human platelet lysate (pHPL) is an efficient alternative to xenogenic supplements for ex vivo expansion of mesenchymal stem cells (MSCs) in clinical studies. Currently, porcine heparin is used in pHPL-supplemented medium to prevent clotting due to plasmatic coagulation factors. We therefore searched for an efficient and reproducible medium preparation method that avoids clot formation while omitting animal-derived heparin.', 'We established a protocol to deplete fibrinogen by clotting of pHPL in medium, subsequent mechanical hydrogel disruption and removal of the fibrin pellet. After primary culture, bone-marrow and umbilical cord derived MSCs were tested for surface markers by flow cytometry and for trilineage differentiation capacity. Proliferation and clonogenicity were analyzed for three passages.', 'The proposed clotting procedure reduced fibrinogen more than 1000-fold, while a volume recovery of 99.5\\xa0% was obtained. All MSC types were propagated in standard and fibrinogen-depleted medium. Flow cytometric phenotype profiles and adipogenic, osteogenic and chondrogenic differentiation potential in vitro were independent of MSC-source or medium type. Enhanced proliferation of MSCs was observed in the absence of fibrinogen but presence of heparin compared to standard medium. Interestingly, this proliferative response to heparin was not detected after an initial contact with fibrinogen during the isolation procedure.",
            "output": [
                "Does mechanical fibrinogen-depletion support heparin-free mesenchymal stem cell propagation in human platelet lysate?"
            ]
        },
        {
            "id": "task847-1d6deb3eeab149f2ae733f10ec4978bb",
            "input": "To assess whether joint pain or radiographic osteoarthritis (ROA) of the knee and hand is associated with all-cause and disease-specific mortality in middle-aged women.', 'Four subgroups from the prospective community-based Chingford Cohort Study were identified based on presence/absence of pain and ROA at baseline: (Pain-/ROA-; Pain+/ROA-; Pain-/ROA+; Pain+/ROA+). Pain was defined as side-specific pain in the preceding month, while side-specific ROA was defined as Kellgren-Lawrence grade \u22652. All-cause, cardiovascular disease (CVD) and cancer-related mortality over the 23-year follow-up was based on information collected by the Office for National Statistics. Associations between subgroups and all-cause/cause-specific mortality were assessed using Cox regression, adjusting for age, body mass index, typical cardiovascular risk factors, occupation, past physical activity, existing CVD disease, glucose levels and medication use.', '821 and 808 women were included for knee and hand analyses, respectively. Compared with the knee Pain-/ROA- group, the Pain+/ROA- group had an increased risk of CVD-specific mortality (HR 2.93 (95% CI 1.47 to 5.85)), while the knee Pain+/ROA+ group had an increased HR of 1.97 (95% CI 1.23 to 3.17) for all-cause and 3.57 (95% CI 1.53 to 8.34) for CVD-specific mortality. We found no association between hand OA and mortality.",
            "output": [
                "Is painful knee but not hand osteoarthritis an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women?"
            ]
        },
        {
            "id": "task847-2722ce183bb149c099de63e640b09e8c",
            "input": "Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease with markedly increased eosinophils, Th2-type lymphocytes, fibroblasts, and goblet cells. Fungi are commonly associated with airway inflammatory diseases, and thymic stromal lymphopoietin (TSLP) is important in the development of Th2 inflammatory responses. The aim of this study was to investigate the interaction between airborne fungi and nasal fibroblasts in TSLP mRNA and protein expression.', 'Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria and Aspergillus, respectively, for 48 hours, and TSLP mRNA and protein expressions were measured. The reverse transcriptase polymerase chain reaction was performed for the Toll-like receptor (TLR) mRNA expression of the nasal fibroblasts. To determine the role of TLR in the induction of TSLP, the fibroblasts were transfected with siRNA against TLR2 and TLR5.', 'Alternaria induced TSLP mRNA and protein expression in both inferior turbinate and nasal polyp fibroblasts. The nasal polyp fibroblasts responded more strongly to the fungi. TLR2 and TLR5 mRNA expressions were significantly increased with fungal stimulation and TSLP production was significantly inhibited by siRNA against TLR2.",
            "output": [
                "Does alternaria induce Production of Thymic Stromal Lymphopoietin in Nasal Fibroblasts Through Toll-like Receptor 2?"
            ]
        },
        {
            "id": "task847-79ec11f66b2b46f7a705194be3fc8ede",
            "input": "Although home renovation exposure during childhood has been identified as a risk factor for the development of allergy, there is limited information on the association between prenatal exposure to home renovation and cord blood (CB) IgE response. The aims of this study were to identify the effect of prenatal exposure to home renovation on CB IgE levels, and to investigate whether this exposure interacts with neonatal genes and whether the effect can be modified by maternal atopy.', 'This study included 1,002 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire. The levels of CB IgE were measured by the ImmunoCAP system, and DNA was extracted from CB.', 'Exposure to home renovation during the prenatal period was associated with significantly higher levels of CB IgE only in neonates from atopic mothers, and the effect of renovation exposure on CB IgE levels persisted from 31 months before birth. Furthermore, prenatal exposure to home renovation increased the risk of CB IgE response interacting with polymorphisms of NRF2 and GSTP1 genes only in neonates from atopic mothers.",
            "output": [
                "Is the Interaction Between Prenatal Exposure to Home Renovation and Reactive Oxygen Species Genes in Cord Blood IgE Response Modified by Maternal Atopy?"
            ]
        },
        {
            "id": "task847-fcb6b3d321224e5491491f169c080772",
            "input": "Natural disasters expose entire communities to stress and trauma, leading to increased risk for psychiatric symptoms. Yet, the majority of exposed individuals are resilient, highlighting the importance of identifying underlying factors that contribute to outcomes.', \"The current study was part of a larger prospective study of children in Long Island, New York (n = 260). At age 9, children viewed unpleasant and pleasant images while the late positive potential (LPP), an event-related potential component that reflects sustained attention toward salient information, was measured. Following the event-related potential assessment, Hurricane Sandy, the second costliest hurricane in United States history, hit the region. Eight weeks after the hurricane, mothers reported on exposure to hurricane-related stress and children's internalizing and externalizing symptoms. Symptoms were reassessed 8 months after the hurricane.\", 'The LPP predicted both internalizing and externalizing symptoms after accounting for prehurricane symptomatology and interacted with stress to predict externalizing symptoms. Among children exposed to higher levels of hurricane-related stress, enhanced neural reactivity to unpleasant images predicted greater externalizing symptoms 8 weeks after the disaster, while greater neural reactivity to pleasant images predicted lower externalizing symptoms. Moreover, interactions between the LPP and stress continued to predict externalizing symptoms 8 months after the hurricane.",
            "output": [
                "Does neural Reactivity to Emotional Stimuli Prospectively predict the Impact of a Natural Disaster on Psychiatric Symptoms in Children?"
            ]
        },
        {
            "id": "task847-d25d16573f144aa39da39fa5ffaf7cca",
            "input": "Peritoneal fibrosis is one of the long-term complications in peritoneal dialysis (PD) patients. Recent evidences have suggested that hydrogen sulfide (H2S) is beneficial in treating various fibrotic diseases, including pulmonary fibrosis, cirrhosis, kidney fibrosis and cardiac hypertrophy. However, no information is known about the effect of H2S on peritoneal fibrosis. In the present study, we investigated the effect of H2S on peritoneal fibrosis and explored its potential mechanisms.', 'We developed a model of peritoneal fibrosis by intraperitoneally injecting 4.25%-glucose PD fluids and lipopolysaccharide to Sprague-Dawley rats. The rats received daily intraperitoneal injections of NaHS (56 \u03bcg/kg), an H2S donor. After 28 days, the peritoneal equilibration test (PET) was used to assess peritoneal function. At the end of dialysis, the rats were killed and parietal peritoneum was harvested for microscopic examination and immunohistochemistry.', 'On the 28th day, the parietal peritoneum of the PD rats markedly thickened as a result of increased depositions of type III collagen and fibronectin. Moreover, the number of ED-1-positive cells and the expressions of monocyte chemoattractant protein-1, transforming growth factor-\u03b21 (TGF-\u03b21), \u03b1-smooth muscle actin and CD31 were significantly increased in the fibrotic peritoneum. Administration of NaHS markedly decreased the biomarkers of inflammation, fibrosis and angiogenesis in the peritoneum. NaHS also improved peritoneal function assessed by PET.",
            "output": [
                "Does hydrogen Sulfide alleviate Peritoneal Fibrosis via Attenuating Inflammation and TGF-\u03b21 Synthesis?"
            ]
        },
        {
            "id": "task847-41c0711caa294df59cdb875993a80b72",
            "input": "To investigate whether programmed death ligand 1 (PD-L1) expressed in the periodontal tissue of chronic periodontitis and the correlativity of PD-L1 and different degrees of chronic periodontitis, provide experience for immunoregulation mechanism, clinical treatment and prognosis of chronic periodontitis.', 'Gingiva and periodontal tissue of healthy people and chronic periodontitis patients were collected. Based on clinical probing, periodontal tissue were classified into three groups: periodontal tissues of healthy people, periodontal tissue of mild chronic periodontitis, periodontal tissue of severe chronic periodontitis. Fluorescent quantitation polymerase chain reaction was applied to explore the expression of PD-L1 mRNA in the periodontal tissue of the different groups. Western blot and immunohistochemistry method were utilized to test the expression of PD-L1 protein in the periodontal tissue of the different groups. Combining with clinical image data, the relationship between differentially expressions of PD-L1 and different degrees of chronic periodontitis was analyzed.', 'The relative expression quantity of PD-L1 in the periodontal tissue of the mild chronic periodontitis was significantly higher that of the severe chronic periodontitis (P<0.01). The relative expression quantity of PD-L1 in the periodontal tissue of healthy subjects and severe chronic periodontitis had no statistical significance (P>0.05).",
            "output": [
                "Does [ Programmed death ligand 1 negatively regulate inflammatory response of chronic periodontitis ]?"
            ]
        },
        {
            "id": "task847-ea404882c2d441b699f70cae06b8961a",
            "input": "Adjusting well academically and socially has been associated with enhanced academic performance and student retention. The purpose of this study was to examine subthreshold levels of ADHD symptoms such as inattention, hyperactivity, and executive functioning as potential predictors of academic and social adjustment in a healthy sample of university students.', 'Participants were 135 undergraduate university students who completed self-report questionnaires.', 'Hierarchical regression analyses revealed that metacognition (an aspect of executive function), gender, and age were significant predictors of academic adjustment beyond hyperactivity, inattention, and depression. Depression was the only significant predictor of social adjustment.",
            "output": [
                "Does executive Functioning predict Academic But Not Social Adjustment to University?"
            ]
        },
        {
            "id": "task847-9257af5b840e405cbdf173bc4be4a7b2",
            "input": "Shoulder instability is a common problem in young athletes and can lead to pain and decreased ability to participate in high-level activities. Little is known about the modifiable risk factors for glenohumeral joint instability.', 'Isometric shoulder strength at baseline would be a modifiable risk factor associated with subsequent first-time anterior instability events.', 'Cohort study.', 'Study participants were freshmen entering the United States Military Academy in June 2006. All participants completed bilateral isometric strength evaluations with a hand-held dynamometer at baseline upon entry into the study. Variables measured included internal and external rotation at 0\u00b0 (IR0, ER0) and internal and external rotation at 45\u00b0 of abduction (IR45, ER45). All subjects were followed for subsequent glenohumeral joint instability events until graduation in May 2010. Independent t tests were used to analyze the data.', 'Baseline strength data were available for 1316 shoulders with no prior history of instability, of which 26 went on to have an acute first-time anterior shoulder instability event while the individuals were at the academy. There were no significant differences in mean strength between shoulders that did not go on to develop instability (uninjured; n = 1290) and those that did develop anterior instability (injured; n = 26). The mean strength values in pounds of force for uninjured and injured shoulders, respectively, were as follows: IR0 (49.80 vs 49.29; P = .88), ER0 (35.58 vs 33.66; P = .27), IR45 (47.38 vs 46.93; P = .88), and ER45 (40.08 vs 38.98; P = .59).",
            "output": [
                "Is rotator Cuff Weakness a Risk Factor for First-Time Anterior Glenohumeral Instability?"
            ]
        },
        {
            "id": "task847-c7a1a22a44504b2fb84825df4d690237",
            "input": "Cardiac malfunction is a common complication in sepsis and significantly increases the mortality of patients in septic shock. However, no studies have examined whether andrographolide (And) reduces LPS-induced myocardial malfunction.', 'Left ventricular systolic and diastolic functions were examined using echocardiography. TNF-\u03b1 and IL-1\u03b2 protein levels were detected by an enzyme-linked immunosorbent assay (ELISA). NO oxidation products were determined using Griess reagent. Protein expression levels of inhibitors of NF-\u03baB\u03b1 (I\u03baB) and phospho-I\u03baB were determined via Western blot. Oxidative injury was determined by measuring myocardial lipid peroxidation and superoxide dismutase activity. Cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) and cardiac caspase 3/7 activity.', 'And blunted LPS-induced myocardial malfunctions in mice. LPS induced TNF-\u03b1, IL-1\u03b2, and NO production as well as I-\u03baB phosphorylation. Cardiac apoptosis was attenuated via incubation with And, but the extent of oxidative injury remained unaffected.",
            "output": [
                "Does andrographolide attenuate LPS-Induced Cardiac Malfunctions Through Inhibition of I\u03baB Phosphorylation and Apoptosis in Mice?"
            ]
        },
        {
            "id": "task847-3862accb923a416a97b0b009e656bb76",
            "input": "Perls' stain is routinely used to demonstrate iron in liver biopsies. We tested the hypothesis that it may be unnecessary in cases, where no iron or another similar pigment was seen on the routine hematoxylin and eosin (H and E) stained section.\", \"The aim of this study was to evaluate the efficiency of H and E stain in demonstrating iron in liver biopsies as well as to determine the possibility of replacing Perls' stain with H and E stain.\", \"Two hundred pairs of slides of liver biopsies were taken from the archival files of the Department of Pathology from 2006 to 2011. Perls' and H and E slides were independently reviewed for the presence of iron.\", \"Hundred and one cases showed the presence of iron using H and E stain. 84 of 86 cases showed positive iron using both Perls' and H and E stains. Seventeen cases were positive using H and E stain but negative with Perls'. Only two cases did not show the presence of iron using H and E stain. Ninety-seven cases were negative using both Perls' and H and E stains. H and E stain showed a sensitivity, specificity, accuracy, positive predictive valve, and negative predictive value of 97.67%, 85.08%, 90.5%, 83.16%, and 97.98%, respectively.",
            "output": [
                "Do hematoxylin and eosin stain shows a high sensitivity but sub-optimal specificity in demonstrating iron pigment in liver biopsies?"
            ]
        },
        {
            "id": "task847-2e38b1478e4c427ab08e7581b10b65a5",
            "input": "DNA replication and transcription are dynamic processes regulating plant development that are dependent on the chromatin accessibility. Proteins belonging to the Agenet/Tudor domain family are known as histone modification \"readers\" and classified as chromatin remodeling proteins. Histone modifications and chromatin remodeling have profound effects on gene expression as well as on DNA replication, but how these processes are integrated has not been completely elucidated. It is clear that members of the Agenet/Tudor family are important regulators of development playing roles not well known in plants.', 'Bioinformatics and phylogenetic analyses of the Agenet/Tudor Family domain in the plant kingdom were carried out with sequences from available complete genomes databases. 3D structure predictions of Agenet/Tudor domains were calculated by I-TASSER server. Protein interactions were tested in two-hybrid, GST pulldown, semi-in vivo pulldown and Tandem Affinity Purification assays. Gene function was studied in a T-DNA insertion GABI-line.', 'In the present work we analyzed the family of Agenet/Tudor domain proteins in the plant kingdom and we mapped the organization of this family throughout plant evolution. Furthermore, we characterized a member from Arabidopsis thaliana named AIP1 that harbors Agenet/Tudor and DUF724 domains. AIP1 interacts with ABAP1, a plant regulator of DNA replication licensing and gene transcription, with a plant histone modification \"reader\" (LHP1) and with non modified histones. AIP1 is expressed in reproductive tissues and its down-regulation delays flower development timing. Also, expression of ABAP1 and LHP1 target genes were repressed in flower buds of plants with reduced levels of AIP1.",
            "output": [
                "Is aIP1 a novel Agenet/Tudor domain protein from Arabidopsis that interacts with regulators of DNA replication , transcription and chromatin remodeling?"
            ]
        },
        {
            "id": "task847-b8d614351fbe4d1ab6b60ad2cb575e00",
            "input": "Pandemic strains of HIV-1 (group M) encode a total of nine structural (gag, pol, env), regulatory (rev, tat) and accessory (vif, vpr, vpu, nef) genes. However, some subtype A and C viruses exhibit an unusual gene arrangement in which the first exon of rev (rev1) and the vpu gene are placed in the same open reading frame. Although this rev1-vpu gene fusion is present in a considerable fraction of HIV-1 strains, its functional significance is unknown.', 'Examining infectious molecular clones (IMCs) of HIV-1 that encode the rev1-vpu polymorphism, we show that a fusion protein is expressed in infected cells. Due to the splicing pattern of viral mRNA, however, these same IMCs also express a regular Vpu protein, which is produced at much higher levels. To investigate the function of the fusion gene, we characterized isogenic IMC pairs differing only in their ability to express a Rev1-Vpu protein. Analysis in transfected HEK293T and infected CD4+ T cells showed that all of these viruses were equally active in known Vpu functions, such as down-modulation of CD4 or counteraction of tetherin. Furthermore, the polymorphism did not affect Vpu-mediated inhibition of NF-\u043aB activation or Rev-dependent nuclear export of incompletely spliced viral mRNAs. There was also no evidence for enhanced replication of Rev1-Vpu expressing viruses in primary PBMCs or ex vivo infected human lymphoid tissues. Finally, the frequency of HIV-1 quasispecies members that encoded a rev1-vpu fusion gene did not change in HIV-1 infected individuals over time.",
            "output": [
                "Does a Naturally Occurring rev1-vpu Fusion Gene Confer a Fitness Advantage to HIV-1?"
            ]
        },
        {
            "id": "task847-fcf52f6714b14465a662124dec246a3b",
            "input": "Multiple intercostal recordings were supposed to get a more comprehensive view of the depolarization vector of the outflow tract ventricular arrhythmia (OT-VA), which may help to identify the OT-VA more accurately. This study was undertaken to develop a more accurate electrocardiogram (ECG) criterion for differentiating between left and right OT-VA origins.', 'We studied OT-VA with a left bundle branch block pattern and inferior axis QRS morphology in 47 patients with successful catheter ablation in the right ventricular OT (RVOT; n = 37) or aortic coronary cusp (ACC; n = 10). Superior and inferior precordial leads were taken together with the routine 12-lead ECG. The ECG during the OT-VA and during sinus beats were analyzed. Transition ratio, transition zone (TZ) index, R/S amplitude ratio, and R-wave duration ratio were measured in the regular, superior, and inferior precordial leads.', 'The combined TZ index, TZ index inferior was significantly smaller, while the V2 inferior transition ratio was significantly larger for ACC origins than RVOT origins (P < 0.05). The area under the curve for the combined TZ index by a receiver operating characteristic analysis was 0.974, which was significantly larger than other parameters. A cutoff value \u22640.25 predicted an ACC origin with 94% sensitivity and 100% specificity. This advantage of the parameter over others also held true for a subanalysis of OT-VAs with a lead V3 precordial transition or TZ index = 0.",
            "output": [
                "Does multiple Intercostal Space Electrocardiogram allow Accurate Localization of Outflow Tract Ventricular Arrhythmia Origin?"
            ]
        },
        {
            "id": "task847-58164d4f21394421806aca4e4b92439d",
            "input": "Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells.', 'Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves.', 'Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 \u03bcg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice.",
            "output": [
                "Does exenatide facilitate Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats?"
            ]
        },
        {
            "id": "task847-80452b4aae4c4157b8fed75bc0287c48",
            "input": "Hyperhomocysteinemia, increased oxidative stress, and decreased antioxidant defense function have been found to be associated with the risk of chronic kidney disease (CKD). Deficiencies of folate and vitamin B-6 (pyridoxal 5'-phosphate, PLP) may cause hyperhomocysteinemia and increased oxidative stress. The purpose of this study was to determine the associations among homocysteine, folate, PLP, oxidative stress indicator, and antioxidant capacities in patients with stage 2 to 3 CKD, and to further analyze these relationships with respect to risk for CKD.\", 'Ninety-seven patients with CKD and 135 healthy subjects were recruited.', 'Patients with CKD had significantly higher levels of malondialdehyde and total antioxidant capacities, but had significantly lower antioxidant enzyme activities compared with healthy subjects. Serum folate but not plasma PLP was significantly negatively associated with plasma homocysteine. There were no significant associations of homocysteine, PLP, and folate with oxidative stress indicator and antioxidant capacities. High homocysteine (odds ratio [OR] = 1.11; 95% confidence interval [CI], 1.02-1.22) and malondialdehyde (OR = 34.24; 95% CI, 4.44-264.40) level increased the risk of CKD, whereas high plasma PLP (OR = 0.98; 95% CI, 0.97-0.99) and superoxide dismutase activity (OR = 0.82; 95% CI, 0.74-0.91) decreased the risk of CKD after adjusting all potential confounders.",
            "output": [
                "Are high homocysteine , low vitamin B-6 , and increased oxidative stress independently associated with the risk of chronic kidney disease?"
            ]
        },
        {
            "id": "task847-1c8be7192e184272b8110ddf1dfed752",
            "input": "Matrix metalloproteinases (MMPs) are the major class of enzymes responsible for degradation of extracellular matrix components and participate in the pathogenesis of periapical inflammatory lesions. MMP expression may be regulated by DNA methylation. The purpose of the present investigation was to analyze the expression of MMP2 and MMP9 in periapical granulomas and radicular cysts and to test the hypothesis that, in these lesions, their transcription may be modulated by DNA methylation.', 'Methylation-specific polymerase chain reaction was used to evaluate the DNA methylation pattern of the MMP2 gene in 13 fresh periapical granuloma samples and 10 fresh radicular cyst samples. Restriction enzyme digestion was used to assess methylation of the MMP9 gene in 12 fresh periapical granuloma samples and 10 fresh radicular cyst samples. MMP2 and MMP9 messenger RNA transcript levels were measured by quantitative real-time polymerase chain reaction.', 'All periapical lesions and healthy mucosa samples showed partial methylation of the MMP2 gene; however, periapical granulomas showed higher MMP2 mRNA expression levels than healthy mucosa (P\\xa0=\\xa0.014). A higher unmethylated profile of the MMP9 gene was found in periapical granulomas and radicular cysts compared with healthy mucosa. In addition, higher MMP9 mRNA expression was observed in the periapical lesions compared with healthy tissues.",
            "output": [
                "Does dNA Methylation of MMP9 be Associated with High Levels of MMP-9 Messenger RNA in Periapical Inflammatory Lesions?"
            ]
        },
        {
            "id": "task847-19eb10aae971402baabf2b4321a242ab",
            "input": "Multiple MicroRNAs (miRNAs) have been identified in the development and progression of lung cancer. However, the expression and roles of miR-132 in non-small cell lung cancer (NSCLC) remain largely undefined. The aim of this study is to investigate the biological functions and its molecular mechanisms of miR-132 in human lung cancer cells.', 'miR-132 expression was measured in human lung cancer cell lines by quantitative real-time PCR (qRT-PCR). The cells migration and invasion ability were measured by wound healing assay and transwell assay. The influence of miR-132 on tumor progression in vivo was monitored using NSCLC xenografts in nude mice. The target gene of miR-132 was determined by luciferase assay and western blot.', 'The expression level of miR-132 was dramatically decreased in examined lung cancer cell lines. Then, we found that introduction of miR-132 significantly suppressed the migration and invasion of lung cancer cells in vitro. Besides, miR-132 overexpression could also inhibit tumor growth in the nude mice. Further studies indicated that the sex determining region Y-box 4 (SOX4) is a target gene of miR-132. SOX4 re-introduction could reverse the anti-invasion role of miR-132.",
            "output": [
                "Does miR-132 inhibit lung cancer cell migration and invasion by targeting SOX4?"
            ]
        },
        {
            "id": "task847-6b8cf459b26647ac9bd839cc74590990",
            "input": "miR-1290 is a newly discovered microRNA (miRNA), and its role in non-small cell lung cancer (NSCLC) remains unknown. This study aimed to evaluate the expression levels of miR-1290 in NSCLC tissues and serum, and explore its associations with clinicopathological characteristics and prognosis of NSCLC patients.', 'A total of 33 pairs of tissues and 73 serum samples were obtained from NSCLC patients and expression levels of miR-1290 were detected by specific TaqMan qRT-PCR. The relationship between miR-1290 expression levels in NSCLC tissues and serum and clinicopathological characteristics was estimated respectively. The correlation between serum miR-1290 expression levels and overall survival of NSCLC patients was performed by Kaplan-Meier analysis and Cox proportional hazards model.', 'We determined that miR-1290 expression levels were increased significantly in NSCLC tissues compared with non-tumor adjacent normal tissues, and higher miR-1290 expression levels were positively correlated with high tumor stage (P=0.004) and positive lymph node metastasis (P=0.013). Compared with benign lung disease and healthy controls, serum levels of NSCLC patients exhibited higher expression of miR-1290. Furthermore, the up-regulation of serum miR-1290 more frequently occurred in NSCLC patients with high TNM stage, positive lymph node metastasis (P=0.022 and P=0.024, respectively). Kaplan-Meier analysis demonstrated that high serum miR-1290 expression levels predicted poor survival (P=0.022). Cox proportional hazards risk analysis indicated that miR-1290 was an independent prognostic factor for NSCLC.",
            "output": [
                "Is miR-1290 a potential prognostic biomarker in non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-0df101fee3104c20907a77b8b293a82f",
            "input": "The role of the cytokine, macrophage migration inhibition factor (MIF) was assessed in tuberculosis. This case-control study investigated whether commonly occurring functional MIF polymorphisms are associated with active tuberculosis as well as with serum levels of MIF, IFN-\u03b3 and TNF-\u03b1.', 'Two MIF promoter polymorphisms, a functional -794 CATT5-8 microsatellite repeat (rs5844572) and a -173G/C single-nucleotide polymorphism (rs755622), were analysed by PCR and PCR-RFLP, respectively, in 47 patients and 50 healthy subjects. The mRNA level of MIF was performed by real-time PCR (RT-PCR), and MIF, IFN-\u03b3 and TNF-\u03b1 serum levels were determined by ELISA.', 'A significant increase of MIF mRNA expression and MIF protein level were found in patients compared to healthy controls. Meanwhile, the increase of IFN-\u03b3 and TNF-\u03b1 serum levels were confirmed. According to the profile of genetic model, a significant association was found of genotypes carrying the -794 CATT 7 or 8 and -173 C risk alleles with susceptibility to active tuberculosis and with a significant increase of MIF, IFN-\u03b3 and TNF-\u03b1.",
            "output": [
                "Are functional polymorphisms in the gene encoding macrophage migration inhibitory factor ( MIF ) associated with active pulmonary tuberculosis?"
            ]
        },
        {
            "id": "task847-c8435683444b416cab4e5dfd24958641",
            "input": "The development of chemo-resistance in non-small lung cancer is a major obstacle in treating patients. Hypoxia is a commonly faced microenvironment in solid tumor and suggested to be related to both autophagy and chemo-resistance.', 'In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue', 'Hypoxic exposure (1 % O2) of A549 cell stimulated autophagic induction in cancer cells, shown by increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 in Western blot, increased GFP-LC puncta in confocal microscopy, and increased number of double-membrane autophagic vacuoles in electron micrographs. Hypoxic exposure also induced resistance of cancer cells to cisplatin, and LC3B siRNA restored the sensitivity of cancer cells to chemotherapy. Furthermore, Human lung cancer tissues that experienced chemotherapy showed increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 compared with chemo-na\u00efve cancer tissue in Western blot.",
            "output": [
                "Does autophagy contribute to the chemo-resistance of non-small cell lung cancer in hypoxic conditions?"
            ]
        },
        {
            "id": "task847-84c3388eff454243b9efa225a583d7a6",
            "input": "The study of inter-individual interactions (often termed spatial-temporal interactions, or dynamic interactions) from remote tracking data has focused primarily on identifying the presence of such interactions. New datasets and methods offer opportunity to answer more nuanced questions, such as where on the landscape interactions occur. In this paper, we provide a new approach for mapping areas of spatial-temporal overlap in wildlife from remote tracking data. The method, termed the joint potential path area (jPPA) builds from the time-geographic movement model, originally proposed for studying human movement patterns.', 'The jPPA approach can be used to delineate sub-areas of the home range where inter-individual interaction was possible. Maps of jPPA regions can be integrated with existing geographic data to explore landscape conditions and habitat associated with spatial temporal-interactions in wildlife. We apply the jPPA approach to simulated biased correlated random walks to demonstrate the method under known conditions. The jPPA method is then applied to three dyads, consisting of fine resolution (15 minute sampling interval) GPS tracking data of white-tailed deer (Odocoileus virginianus) collected in Oklahoma, USA. Our results demonstrate the ability of the jPPA to identify and map jPPA sub-areas of the home range. We show how jPPA maps can be used to identify habitat differences (using percent tree canopy cover as a habitat indicator) between areas of spatial-temporal overlap and the overall home range in each of the three deer dyads.",
            "output": [
                "Do mapping areas of spatial-temporal overlap from wildlife tracking data?"
            ]
        },
        {
            "id": "task847-a6a12dc28bf3451bafd9a4d159d2d82a",
            "input": "Different apoptosis pathways activate caspase-3. In a study involving 27 patients with traumatic brain injury (TBI), higher caspase-3 levels were found in contusion brain tissue resected from non-survivors than from survivors. The objective of this study was to determine whether there is an association in TBI patients between serum caspase-3 levels (thus using an easier, quicker, less expensive and less invasive procedure) and mortality, in a larger series of patients.', 'We carried out a prospective, observational and multicenter study in six Spanish Hospital Intensive Care Units including 112 patients with severe TBI. All had Glasgow Coma Scale (GCS) scores lower than 9. Patients with an Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Blood samples were collected on day 1 of TBI to measure serum caspas-3 levels. The endpoint was 30-day mortality.', 'We found that non-surviving patients (n = 31) showed higher (p = 0.003) serum caspase-3 levels compared to survivors (n = 81). Kaplan-Meier survival analysis showed a higher risk of death in TBI patients with serum caspase-3 levels >0.20 ng/mL than in patients with lower concentrations (Hazard Ratio = 3.15; 95% CI = 1.40 to 7.08; P < 0.001). Multiple logistic regression analysis showed that serum caspase-3 levels > 0.20 ng/mL were associated with mortality at 30 days in TBI patients controlling for Marshall CT classification, age and GCS (Odds ratio = 7.99; 95% CI = 2.116 to 36.744; P = 0.001).",
            "output": [
                "Are serum caspase-3 levels and mortality associated in patients with severe traumatic brain injury?"
            ]
        },
        {
            "id": "task847-42753a9a93a94dac9447ed1baf86c33c",
            "input": "Our aim was to investigate if: (a) authors of Biochemia Medica meet authorship criteria given by International Committee of Medical Journal Editors (ICMJE), (b) authorship violations are more frequent in submissions containing some type of scientific misconduct.', 'Self-reported authorship contributions regarding the three ICMJE criteria were analysed for all submissions to Biochemia Medica (February 2013-April 2015) which were forwarded to peer-review. To test the differences in frequencies we used Chi-squared test. P<0.05 was considered statistically significant.', '186 manuscripts were authored by 804 authors. All ICMJE criteria were met by 487/804 (61%) authors. The first and the last author met all the criteria more frequently than those authors in between (P<0.001). The degree to which ICMJE criteria was met for the first author did not differ between manuscripts authored by only one author and those authored by >1 author (P=0.859). In 9% of the manuscripts ICMJE criteria were not met by a single author. Authors of the 171/186 manuscripts declared that all persons qualify for authorship but only 49% of them satisfied all ICMJE criteria. Authors have failed to acknowledge contributors in 88/186 (47%) manuscripts; instead these contributors have been listed as authors without fulfilling ICMJE criteria. Authorship violation was not more common in 42 manuscripts with some type of scientific misconduct (P=0.135).",
            "output": [
                "Are iCMJE authorship criteria met in a substantial proportion of manuscripts submitted to Biochemia Medica?"
            ]
        },
        {
            "id": "task847-7da4a05338df462ca56b98549a127d85",
            "input": "Morphology and material properties are the main components of the mechanical design of organisms, with species groups developing different optimization strategies in the context of their physical environment. For intertidal and subtidal seaweeds, possessing highly flexible and extensible tissues allows individuals to bend and reconfigure in flow, thereby reducing drag. Previous research has shown that aging may compromise these qualities. Tissue age increases with distance from the blade's meristem, which differs in its position on kelps and red algae. Here, we assess whether longitudinal patterns of blade material properties differ between these two algal groups according to tissue age.\", 'We performed tensile tests on tissues samples excised from various positions along the extent of blades in nine kelp species (basal growth) and 15 species of red algae (apical growth).', \"We found that older tissues were less flexible and extensible than younger tissues in all species tested. As predicted, tissue near the basal meristem in kelp was more flexible and extensible than older tissue at the blade's distal end. The opposite pattern was observed for red algae, with the most flexible and extensible tissues found near the apical meristem at the distal ends of blades.",
            "output": [
                "Do divergent growth strategies between red algae and kelps influence biomechanical properties?"
            ]
        },
        {
            "id": "task847-71ae9991be1e4194be0a7fed9b3898cd",
            "input": "Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range.', \"We studied 3533 male participants of the Aragon Workers' Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration.",
            "output": [
                "Is lower-normal TSH associated with better metabolic risk factors : A cross-sectional study on Spanish men?"
            ]
        },
        {
            "id": "task847-7dea60b7a8bf4ff0bf8c9be223052113",
            "input": "In heart failure, a holistic approach incorporating the patient's perspective is vital for prognosis and treatment. Self-rated health has strong associations with adverse events and short-term mortality risk, but long-term data are limited. We investigated the predictive value of two consecutive self-rated health assessments with regard to long-term mortality in a large, well characterised sample of elderly patients with stable chronic heart failure.\", \"We measured self-rated health by asking 'In general, would you say your health is: 1, excellent; 2, very good; 3, good; 4, fair; 5, poor?' twice: at baseline and the end of a 12-week beta-blocker up-titration period in the CIBIS-ELD trial. Mortality was assessed in an observational follow-up after 2-4 years. A total of 720 patients (mean left ventricular ejection fraction 45\u00b112%, mean age 73\u00b15 years, 36% women) rated their health at both time points. During long-term follow-up, 144 patients died (all-cause mortality 20%). Fair/poor self-rated health in at least one of the two reports was associated with increased mortality (hazard ratio 1.42 per level; 95% confidence interval 1.16-1.75; P<0.001). It remained independently significant in multiple Cox regression analysis, adjusted for N-terminal pro B-type natriuretic peptide (NTproBNP), heart rate and other risk prediction covariates. Self-rated health by one level worse was as predictive for mortality as a 1.9-fold increase in NTproBNP.",
            "output": [
                "Does poor self-rated health predict mortality in patients with stable chronic heart failure?"
            ]
        },
        {
            "id": "task847-810b34e1339748b0b85a4be960db1295",
            "input": "Previous research has suggest that obesity is associated with increased risk for psychopathological disorders, however, little is known about which obese patients are most vulnerable to psychopathological disorders. We therefore investigated 126 treatment-seeking obese women to describe eating disorder pathology and mental health correlates, and to identify disordered eating behaviors that may place obese at increased risk for psychopathological disorders.', 'The Structured Clinical Interview for DSM-IV (SCID) was used to identify Eating Disorders (ED). A battery of psychological tests, including the Anxiety Scale Questionnaire (ASQ,) Clinical Depression Questionnaire (CDQ), Eating Disorder Inventory-2 (EDI-2) Eating Attitudes Test-26 (EAT-26) scales and structured clinical interview were administered to all the patients. We analyzed the link between psychopathological disorders and eating attitudes by using both multiple regression analysis and non-parametric correlation.', 'Disordered eating behaviors and emotional behavioral aspects related to Anorexia Nervosa, such as ineffectiveness, are strongly linked to the depression and anxiety in obese subjects. No correlation was found between psychopathological disorders and age or anthropometric measurements.",
            "output": [
                "Does disordered eating behavior and mental health correlate among treatment seeking obese women?"
            ]
        },
        {
            "id": "task847-01e96762af254144beee5c44f5fd1b6a",
            "input": "Post kala-azar dermal leishmaniasis (PKDL) is a neglected parasitic disease that occurs after apparent cure from visceral leishmaniasis (VL) and poses a challenge for elimination of VL, being its proposed reservoir. Several epidemiological studies have proposed that sex hormones may account for the increased susceptibility of males towards infectious diseases, including leishmaniasis; however, the role of testosterone and sex bias, if any, in PKDL has not been evaluated.', 'The study population included 87 patients with PKDL and 39 with VL; levels of testosterone were measured by competitive enzyme-linked immunosorbent assay along with their levels of antileishmanial immunoglobulin and IgG. The association of testosterone, if any, was then correlated with age, gender, humoral response, lesional profile, disease duration, and lag period.', 'A male predominance was evident in PKDL, not in VL; importantly, this male bias was predominant postpubertal, strongly indicative of an association between sex hormone and disease progression. Male patients with PKDL had significantly higher levels of testosterone, which regressed significantly with miltefosine, not with sodium antimony gluconate. Additionally, a significant correlation was found between plasma testosterone and antileishmanial IgG.",
            "output": [
                "Is a male preponderance in patients with Indian post kala-azar dermal leishmaniasis associated with increased circulating levels of testosterone?"
            ]
        },
        {
            "id": "task847-be95b6ba07d84a3089acf18d0b451508",
            "input": "The aim of this clinical study were to compare the clinical efficacy of ankaferd blood stopper (ABS) when used in combination with autogenous cortical bone graft (ACB) in the treatment of intrabony periodontal defects.', 'The study was planned as a split-mouth design. Fifteen patients with chronic periodontitis at 30 sites (six men, nine women; 42 \u00b1 7 years) were included. Treatment sites had probing pocket depths (PPD) of \u2265 6 mm and osseous defect depths of \u2265 4 mm as radiographically assessed. Following the initial periodontal therapy, patients were randomly assigned to two treatments in contralateral areas of the dentition: ACB + ABS or ACB alone. At baseline and 6 mo after surgery, clinical parameters of plaque index, gingival index, PPD, clinical attachment level and gingival recession (GR) were recorded. The primary outcome variable was the change in clinical attachment level between baseline and 24 wk after surgery. Gingival crevicular fluid samples were collected immediately before surgery and at 2, 4, 6, 12 and 24 wk after the surgery. Gingival crevicular fluid volume was calculated and vascular endothelial growth factor levels in gingival crevicular fluid were measured.', 'PPD decreased, clinical attachment level improved and gingival index decreased significantly in response to both modes of treatment (p < 0.05). Both treatment modalities resulted in a significant gain in radiographic bone levels compared to baseline (p < 0.05). Intergroup comparisons showed that there was a significantly higher gain in clinical attachment level in the ABS/ACB group compared to ACB group (p < 0.05) with significantly less GR (p < 0.05). Similarly, vascular endothelial growth factor concentration in gingival crevicular fluid was significantly higher in the ABS/ACB group at postoperative weeks 2 and 4 compared to the ACB group (p < 0.01).",
            "output": [
                "Does ankaferd blood stopper enhance healing after osseous grafting in patients with intrabony periodontal defects?"
            ]
        },
        {
            "id": "task847-2fef9f69355a4e6e83174906ac4a0efc",
            "input": "We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis.', 'Rat fetuses (n=117) with surgically created gastroschisis were divided into three groups: untreated animals (n=62) and two groups receiving volume-matched intraamniotic injections of either saline (n=25) or 2 \u00d7 10(6) cells/mL of syngeneic, labeled afMSCs (n=30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P<0.05).', 'Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P=0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P=0.003/0.05/<0.001/0.026, respectively). There were no such significant differences between the untreated and saline groups. There were no differences between the afMSC group and NL, except for a significantly thicker muscular layer in the afMSC group (P=0.014). Labeled afMSCs were scarcely identified, suggesting a paracrine effect.",
            "output": [
                "Does transamniotic stem cell therapy ( TRASCET ) mitigate bowel damage in a model of gastroschisis?"
            ]
        },
        {
            "id": "task847-88df5300da9a41a39753649c969783e2",
            "input": "The results of studies examining the influence of subclinical hypothyroidism (SCH) and levothyroxine (L-T4) replacement therapy on bone have generated considerable interest but also controversy. The present research aims to evaluate the effects of L-T4 treatment on different skeletal sites in women.', 'A group of 45 premenopausal (mean age: 43.62 \u00b16.65 years) and 180 postmenopausal (mean age: 59.51 \u00b17.90 years) women with SCH who were undergoing L-T4 replacement therapy for at least 6 months were compared to 58 pre- and 180 postmenopausal women with SCH (untreated) matched for age. The mean doses of L-T4 were 90.88 \u00b142.59 \u00b5g/day in the premenopausal women and 86.35 \u00b134.11 \u00b5g/day in the postmenopausal women. Bone measurements were obtained using quantitative bone ultrasound (QUS) for the phalanx, dual-energy X-ray absorptiometry (DXA) for the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT) for the non-dominant distal forearm.', 'No differences were observed between patients and untreated controls in these bone measurements except in the bone mineral density (BMD) of the spine (p = 0.0214) in postmenopausal women, which was greater in treated women than in untreated controls.",
            "output": [
                "Does treatment of subclinical hypothyroidism affect bone mass as determined by dual-energy X-ray absorptiometry , peripheral quantitative computed tomography and quantitative bone ultrasound in Spanish women?"
            ]
        },
        {
            "id": "task847-4e79582b774f4af2b255767dbc412238",
            "input": "Co-morbid personality disorder (PD) is associated with poorer outcomes in psychosis patients, but it is not known whether these patterns are present at illness onset. This study investigated the prevalence of co-morbid PD in clients of an Early Intervention in Psychosis Service (EIPS) and compared key worker engagement and service use between patients with and without co-morbid PD.', 'Forty-nine participants were recruited from an inner London NHS EIPS. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Axis II Disorders was administered to identify whether participants met criteria for a diagnosis of PD. Key workers completed measures investigating the therapeutic relationship and emotional involvement. Data on service use over a 2-year period from the date on which the patient was accepted by the EIPS were collected from electronic clinical records. Service use and key worker informed data were collected blind to PD diagnosis.', 'Twenty-two of the 49 (45%) patients met criteria for co-morbid PD. Keyworker worry and tension were significantly higher in relation to patients with co-morbid PD compared with those without. There were no significant differences between groups in appointments offered or attended, but patients with co-morbid PD were significantly less likely to be admitted to hospital than those without.",
            "output": [
                "Is co-morbid personality disorder in early intervention psychosis clients associated with greater key worker emotional involvement?"
            ]
        },
        {
            "id": "task847-fab6d9eb2d1d4ad5b65fd192ae1f2276",
            "input": "Homeobox genes are often deregulated in cancer and can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. CDX2 has been implicated in differentiation, proliferation, cell adhesion, and migration. In this study, we investigated CDX2 mRNA and protein expression in relation to the clinicopathological characteristics of colon cancer, including mismatch repair status and recurrence risk.', 'Tumor samples were obtained from colon cancer patients. Biopsies from tumor tissue and normal adjacent tissue were fixed in liquid nitrogen for RNA extraction or in formalin and paraffin embedded (FFPE) for immunohistochemical staining. CDX2 mRNA expression was evaluated by RT-qPCR. FFPE sections were stained for MLH1, MSH2, MSH6, PMS2, and CDX2.', 'A total of 191 patient samples were included in the study and analyzed by immunohistochemistry. Of these samples, 97 were further evaluated by RT-qPCR. There was no significant difference in CDX2 mRNA expression between tumor and normal tissues. CDX2 mRNA expression was significantly lower in right-sided tumors (p<0.05), poorly differentiated tumors (p<0.05), and MMR-deficient tumors (p<0.05). Similarly, CDX2 protein expression was more often low or absent in right-sided tumors (p<0.01), poorly differentiated tumors (p<0.001), and MMR-deficient tumors (p<0.001). Low CDX2 protein or mRNA expression was not associated with recurrence risk.",
            "output": [
                "Is cDX2 downregulation associated with poor differentiation and MMR deficiency in colon cancer?"
            ]
        },
        {
            "id": "task847-2ddc7c49362d43d9aeeb07f482d55e3e",
            "input": "Fibroblast growth factors (FGFs) are crucial signaling molecules that direct the development of the vertebrate brain. FGF8 gene signaling in particular, may be important for the development of the hypothalamus-pituitary-adrenal (HPA)-axis. Indeed, newborn Fgf8 hypomorphic mice harbor a major reduction in the number of vasopressin (VP) neurons in the paraventricular nucleus (PVN), the central output component of the HPA-axis. Additionally, recent studies indicated that adult heterozygous ((+/neo)) Fgf8 hypomorphic mice exhibit more anxiety-like behaviors than wildtype (WT) mice. These studies led us to investigate whether Fgf8 hypomorphy abrogated VP and/or corticotropin-releasing hormone (CRH) neuronal development in the postnatal day (PN) 21 and adult mouse PVN. Furthermore, we studied whether Fgf8 hypomorphy disrupted HPA responsiveness in these mice.', 'Using immunohistochemistry, we examined the development of VP and CRH neurons located in the PVN of PN 21 and adult Fgf8 (+/neo) mice. Moreover, we used a restraint stress (RS) paradigm and measured corticosterone levels with enzyme immunoassays in order to assess HPA axis activation.', 'The number of VP neurons in the PVN did not differ between WT and Fgf8 (+/neo) mice on PN 21 and in adulthood. In contrast, CRH immunoreactivity was much higher in Fgf8 (+/neo) mice than in WT mice on PN 21, this difference was no longer shown in adult mice. RS caused a higher increase in corticosterone levels in adult Fgf8 (+/neo) mice than in WT mice after 15\\xa0min, but no difference was seen after 45\\xa0min.",
            "output": [
                "Does fibroblast growth factor 8 regulate postnatal development of paraventricular nucleus neuroendocrine cells?"
            ]
        },
        {
            "id": "task847-6b6e6f4061904a5d87a5f1fbb13c1b22",
            "input": "Changes of volume status can be readily inferred from variations in diameter of the inferior vena cava (IVC) measured by ultrasound. However the effect of IVC changes following acute blood loss are not fully established. In this study, three different approaches to measuring IVC variables were compared in healthy blood donors, as a model of acute volume depletion, in order to establish their relative ability to detect acute blood loss.', 'Inspiratory and expiratory IVC diameters were measured before and after blood donation in hepatic long axis, hepatic short axis and renal short axis views using a 2-5\\xa0MHz curvilinear probe. All measurements were recorded and examined in real-time and post-processing sessions.', 'All windows performed satisfactorily but the renal window approach was feasible in only 30 out of 47 subjects. After blood donation, IVC diameters decreased in hepatic long axis, hepatic short axis and renal short axis (expiratory: -19.9, -18.0, -26.5\\xa0%; CI 95\\xa0%: 14.5-24.1; 13.1-22.9; 16.0-35.9, respectively) (inspiratory: -31.1, -31.6, -36.5\\xa0%; CI 95\\xa0%: 21.3-40.1; 18.8-45.2; 23.4-46.0, respectively), whereas the IVC collapsibility index increased by 21.6, 22.6 and 19.3\\xa0% (CI 95\\xa0%: 11.6-42.9; 18.5-39.5; 7.7-30.0). IVC diameters appeared to return to pre-donation values within 20\\xa0min but this was only detected by the hepatic long axis view.",
            "output": [
                "Do inferior vena cava diameters and collapsibility index reveal early volume depletion in a blood donor model?"
            ]
        },
        {
            "id": "task847-7a61b6f9e31a488bb3ee85fa6584706f",
            "input": "Protein arginine methyltransferase 5 (PRMT5), a type II PRMT, is highly expressed in some tumors, but its role in hepatocellular carcinoma (HCC) is still unknown.', 'PRMT5 level in HCC specimens was determined by immunohistochemical staining and the association with clinicopathologic features was evaluated. PRMT5 was inhibited by AMI-1 (a small molecule inhibitor of PRMTs) or small interference RNA (siRNA). The proliferation of HCC cells was tested by Cell Counting Kit-8, cell migration was evaluated by Transwell assay and cell cycle and apoptosis were analyzed by flow cytometry. The effect of AMI-1 on HCC in vivo was examined by mouse xenograft model.', 'PRMT5 expression was markedly upregulated in HCC tissues, and correlated inversely with overall patient survival. Knockdown of PRMT5 significantly reduced the proliferation of HCC cells, but did not affect the growth of normal liver cells. Furthermore, \u03b2-catenin was identified as a target of PRMT5. Silencing PRMT5 significantly down-regulated the expression of \u03b2-catenin and the downstream effector Cyclin D1 in HCC cells. AMI-1 strongly inhibited HCC growth in vivo, increased the ratio of Bax/Bcl-2, and led to apoptosis and loss of migratory activity in several HCC cells. Meanwhile, AMI-1 decreased the expression levels of symmetric dimethylation of H4 (H4R3me2s), a histone mark of PRMT5.",
            "output": [
                "Does targeting protein arginine methyltransferase 5 inhibit human hepatocellular carcinoma growth via the downregulation of beta-catenin?"
            ]
        },
        {
            "id": "task847-056dd47f547a4f9490c9e8f5f761d17c",
            "input": "This study aims to describe trinitrotoluene (TNT)-induced endoplasmic reticulum stress (ERS) and apoptosis in HePG2 cells.', 'HePG2 cells were cultured in vitro with 0, 6, 12, or 24 \u03bcg/ml TNT solution for 12, 24, and 48 h. Western blotting was performed to detect intracellular ERS-related proteins, including glucose-regulated protein (GRP) 78, GRP94, Caspase 4, p-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP). Real-time PCR was used to measure mRNA expression from the respective genes.', 'The expressions of ERS-related proteins GRP78 and GRP94 as well as mRNA and protein expression of ERS signaling apoptotic CHOP in the TNT treatment group were significantly increased. In addition, the mRNA and protein expression levels of ERS-induced apoptotic protein Caspase-4 were significantly increased. Flow cytometry revealed that after TNT treatment, the apoptosis rate also significantly increased.",
            "output": [
                "Does trinitrotoluene induce Endoplasmic Reticulum Stress and Apoptosis in HePG2 Cells?"
            ]
        },
        {
            "id": "task847-2e87d177429d470cbaecebbc479b15b8",
            "input": "Interleukin-17A is a proinflammatory cytokine known to play a role in host defense and pathologic inflammation in murine models of lung injury. The relationship between interleukin-17A and inflammation in human lung injury is unknown. Our primary objective was to determine whether interleukin-17A levels are associated with alveolar measures of inflammation and injury in patients with acute respiratory distress syndrome. Our secondary objective was to test whether interleukin-17A levels are associated with acute respiratory distress syndrome-related outcomes.', 'Observational study.', 'Six North American medical centers.', 'We studied two groups of patients with acute respiratory distress syndrome: 1) patients previously enrolled in a placebo-controlled clinical trial of omega-3 fatty acids performed at five North American medical centers (n = 86, acute respiratory distress syndrome 1), and 2) patients with systemic inflammatory response syndrome admitted to an ICU who developed acute respiratory distress syndrome (n = 140, acute respiratory distress syndrome 2). In acute respiratory distress syndrome 1, we used paired serum and bronchoalveolar lavage fluid samples obtained within 48 hours of acute respiratory distress syndrome onset, whereas in acute respiratory distress syndrome 2, we used plasma obtained within the first 24 hours of ICU admission.', 'None.', 'We measured circulating interleukin-17A in acute respiratory distress syndrome 1 and acute respiratory distress syndrome 2. We also measured interleukin-17A, neutrophil counts, and total protein in bronchoalveolar lavage fluid from acute respiratory distress syndrome 1. We found that bronchoalveolar lavage interleukin-17A was strongly associated with higher bronchoalveolar lavage percent neutrophils (p < 0.001) and bronchoalveolar lavage total protein (p < 0.01) in acute respiratory distress syndrome1. In both acute respiratory distress syndrome 1 and acute respiratory distress syndrome 2, elevated interleukin-17A was associated with higher Sequential Organ Failure Assessment scores (p < 0.05).",
            "output": [
                "Does interleukin-17A be Associated With Alveolar Inflammation and Poor Outcomes in Acute Respiratory Distress Syndrome?"
            ]
        },
        {
            "id": "task847-3ecffed6b9d24196ad7f3c94ecec7481",
            "input": "Gestational diabetes mellitus (GDM) is a disease often manifests in mid to late pregnancy with symptoms including hyperglycemia, insulin resistance and fetal mal-development. The C57BL/KsJ-Lep (db/+) (db/+) mouse is a genetic GDM model that closely mimicked human GDM symptoms. Resveratrol (RV) is a naturally existing compound that has been reported to exhibit beneficial effects in treating type-2 diabetes.', 'In this study, we investigated the effect of RV on the pregnant db/+ GDM mouse model, and the underlying molecular mechanism.', 'RV greatly improved glucose metabolism, insulin tolerance and reproductive outcome of the pregnant db/+ females. Moreover, we found that RV relieved GDM symptoms through enhancing AMPK activation, which in turn reduced production and activity of glucose-6-phosphatase in both pregnant db/+ females and their offspring.",
            "output": [
                "Does resveratrol relieve gestational diabetes mellitus in mice through activating AMPK?"
            ]
        },
        {
            "id": "task847-7e2186215c4d443c8279ac66b14b14ff",
            "input": "Patients with mastocytosis and wasp venom allergy (WA) may benefit from venom immunotherapy (VIT). However, fatal insect sting reactions have been described in mastocytosis patients despite previous immunotherapy. We investigated the safety and efficacy of (rush) VIT in patients with mastocytosis and WA.', 'To investigate the safety and efficacy of (rush) VIT in patients with mastocytosis and WA.', 'We describe nine patients with cutaneous mastocytosis and WA who received VIT. Cutaneous mastocytosis was confirmed by histopathology and systemic mastocytosis was diagnosed according to World Health Organization criteria. VIT was given according to a rush protocol. Given the difference in safety and efficacy of VIT in patients with WA and honeybee venom allergy, we reviewed the literature for VIT with the focus on WA patients with mastocytosis and addressed the difference between patients with cutaneous versus systemic mastocytosis.', 'Nine patients had WA and mastocytosis, of whom six had cutaneous mastocytosis, two combined cutaneous and systemic mastocytosis and one systemic mastocytosis. All patients received rush IT with wasp venom. Most patients had only mild local side effects, with no systemic side effects during the course of VIT. One patient had a systemic reaction upon injection on one occasion, during the updosing phase, with dyspnoea and hypotension, but responded well to treatment. Immunotherapy was continued after temporary dose adjustment without problems. Two patients with a previous anaphylactic reaction were re-stung, without any systemic effects.",
            "output": [
                "Does rush immunotherapy for wasp venom allergy seem safe and effective in patients with mastocytosis?"
            ]
        },
        {
            "id": "task847-8419f59e7c2d42028b42bf50b97cb058",
            "input": "Low-level vagus nerve stimulation (LL-VNS) has been demonstrated to protect myocardium against acute ischemia/reperfusion (I/R) injury. However, the underlying mechanism of this protective effect remains unknown.', 'This study aimed to test the hypothesis that LL-VNS exerts cardioprotective effect on acute I/R injury in canines via antioxidative stress and antiapoptosis reactions.', 'Thirty anesthetized mongrel dogs were randomly divided into three groups: I/R group (N = 12, the left anterior descending coronary artery was occluded for 1 hour following by 1 hour reperfusion), LL-VNS group (N = 9, I/R plus LL-VNS), and sham group (N = 9, sham surgery without LL-VNS). The voltage threshold was set at 80% of the voltage required to slow the sinus rate. Infarct size was assessed with Evans Blue and triphenyltetrazolium chloride. Activity assays, TUNEL staining, and western blotting were performed to determine markers of oxidative stress and apoptosis.', 'LL-VNS significantly decreased the incidence of ventricular arrhythmias, increased vagal tone, as confirmed by heart rate viability, and reduced infarct size compared with the I/R group. This improvement was associated with a reduction in myocardial neutrophil infiltration, the inhibition of oxidative stress, and the suppression in cardiomyocyte apoptosis. In contrast, the lack of LL-VNS in the I/R group induced the opposite effect compared with the sham group.",
            "output": [
                "Does low-Level Vagus Nerve Stimulation attenuate Myocardial Ischemic Reperfusion Injury by Antioxidative Stress and Antiapoptosis Reactions in Canines?"
            ]
        },
        {
            "id": "task847-89dddf3d4a544b4eb3b56855d0ac8b4b",
            "input": "The initial staging work-up of gastric mucosa-associated lymphoid tissue (MALT) lymphoma includes bone marrow examination. Since gastric MALT lymphoma is mostly detected in early stages with the national cancer screening programme in Korea, bone marrow is rarely involved.', 'To investigate the incidence of bone marrow involvement in gastric MALT lymphomas and the role of bone marrow examination for an initial staging work-up.', 'Patients diagnosed with gastric MALT lymphoma at Seoul National University Hospital from January 2005 to July 2014 were enrolled. Clinical databases of the patients were retrospectively reviewed.', 'Out of 105 patients, 91 (86.7%) were classified as stage IE1. Among these patients, 78 patients with Helicobacter pylori infection underwent eradication therapy, and complete remission was achieved in 74 cases (94.9%). Twelve out of 13 patients (92.3%) without H. pylori infection underwent radiotherapy or surgery and all achieved complete remission. Bone marrow involvement was proven in only one patient (1.0%).",
            "output": [
                "Is bone marrow involvement rare in superficial gastric mucosa-associated lymphoid tissue lymphoma?"
            ]
        },
        {
            "id": "task847-9732f608e8734335a060b4354d7bb7cd",
            "input": "-Colorectal carcinoma is the third most common cause of cancer death in males and females in the United States. Rectal adenocarcinoma can have distinct therapeutic and surgical management from colonic adenocarcinoma owing to its location and anatomic considerations.', '-To determine the oncologic driver mutations and better understand the molecular pathogenesis of rectal adenocarcinoma in relation to colon adenocarcinoma.', '-Next-generation sequencing was performed on 20 cases of primary rectal adenocarcinoma with a paired lymph node or solid organ metastasis by using an amplicon-based assay of more than 2800 Catalogue of Somatic Mutations in Cancer (COSMIC)-identified somatic mutations.', '-Next-generation sequencing data were obtained on both the primary tumor and metastasis from 16 patients. Most rectal adenocarcinoma cases demonstrated identical mutations in the primary tumor and metastasis (13 of 16, 81%). The mutations identified, listed in order of frequency, included TP53, KRAS, APC, FBXW7, GNAS, FGFR3, BRAF, NRAS, PIK3CA, and SMAD4.",
            "output": [
                "Does next-Generation Sequencing of Matched Primary and Metastatic Rectal Adenocarcinomas demonstrate Minimal Mutation Gain and Concordance to Colonic Adenocarcinomas?"
            ]
        },
        {
            "id": "task847-32e49bd0a82e480fa0efd31e417832b6",
            "input": "Arteriovenous fistulas (AVFs) are commonly used during hemodialysis. Early failure of AVFs is quite common with incidence of 43% to 63%. In this study we aimed to describe a novel approach to AVF surgery for improving early patency rates.', 'Patients were divided into two groups according to use of probing and warm-wash-out technique. Group I consisted of 31 patients with additional probing technique. Group II consisted of 32 patients without additional maneuver. End-to-side anastomosis were used to all patients. Technical success was defined as having palpation of a thrill on fistula. Flow rates of draining vein was measured at 1st hour, 24th hour, 1st week and 3rd week of surgery.', 'Classical maneuvers were performed until end of the anastomosis. At this time, vein lumen was washed by low-dosed heparinized warm fluid, with assistance of a simple catheter.', 'Technical success was similar in both groups at 1st hour and 24th hour, while there were significantly differences between groups at 1st week (p = 0.042) and 3rd week (p = 0.05) assessments. Flow rates were also measured significantly higher in Group I at 1st hour (p = 0.011) and 24th hour (p = 0.016). Flow rates were almost similar in two groups at 1st and 3rd weeks but overall success rate was higher in Group I comparing with Group II (96.8% vs. 81.3%, respectively, p = 0.05).",
            "output": [
                "Does new probing and warm-wash-out technique improve early patency rates in arteriovenous fistula surgery?"
            ]
        },
        {
            "id": "task847-4b3b37e38807477193f82eb6dabaec11",
            "input": "DNA methylation at CpG dinucleotides is modified in tumorigenesis with potential impact on transcriptional activity.', 'We used the Illumina 450 K platform to evaluate DNA methylation patterns of 50 metastatic melanoma tumors, with matched gene expression data.', 'We identified three different methylation groups and validated the groups in independent data from The Cancer Genome Atlas. One group displayed hypermethylation of a developmental promoter set, genome-wide demethylation, increased proliferation and activity of the SWI/SNF complex. A second group had a methylation pattern resembling stromal and leukocyte cells, over-expressed an immune signature and had improved survival rates in metastatic tumors (p < 0.05). A third group had intermediate methylation levels and expressed both proliferative and immune signatures. The methylation groups corresponded to some degree with previously identified gene expression phenotypes.",
            "output": [
                "Are dNA methylation subgroups in melanoma associated with proliferative and immunological processes?"
            ]
        },
        {
            "id": "task847-72fdcaa924e74c13827432399b6e4825",
            "input": "A patient with a suspected cervical spine injury may be at risk for secondary neurologic injury when initially placed and repositioned to the center of the spine board.', 'We sought to determine which centering adjustment best limits cervical spine movement and minimizes the chance for secondary injury.', 'Using five lightly embalmed cadaveric specimens with a created global instability at C5-C6, motion sensors were anchored to the anterior surface of the vertebral bodies. Three repositioning methods were used to center the cadavers on the spine board: horizontal slide, diagonal slide, and V-adjustment. An electromagnetic tracking device measured angular (degrees) and translation (millimeters) motions at the C5-C6 level during each of the three centering adjustments. The dependent variables were angular motion (flexion-extension, axial rotation, lateral flexion) and translational displacement (anteroposterior, axial, and medial-lateral).', 'The nonuniform condition produced significantly less flexion-extension than the uniform condition (p\\xa0=\\xa00.048). The horizontal slide adjustment produced less cervical flexion-extension (p\\xa0=\\xa00.015), lateral bending (p\\xa0=\\xa00.003), and axial rotation (p\\xa0=\\xa00.034) than the V-adjustment. Similarly, translation was significantly less with the horizontal adjustment than with the V-adjustment; medial-lateral (p\\xa0=\\xa00.017), axial (p\\xa0<\\xa00.001), and anteroposterior (p\\xa0=\\xa00.006).",
            "output": [
                "Does horizontal Slide create Less Cervical Motion When Centering an Injured Patient on a Spine Board?"
            ]
        },
        {
            "id": "task847-76d1ab08075f4081b2b15b1fb4b5231a",
            "input": "Patients with type 2 diabetes mellitus (T2DM) have a high risk of fracture although they have slightly higher bone mineral density (BMD). There is no evidence that dipeptidyl peptidase-4 (DPP-4) is involved in the bone fragility of the patients. The aim of this study was to investigate the association between serum DPP-4 levels and vertebral fractures (VFs) in men with T2DM.', 'We conducted a cross-sectional study and investigated the relationships between serum DPP-4 levels vs BMD at lumbar spine, femoral neck and radius, bone turnover markers and presence of VFs in 204 Japanese male patients.', 'Multiple regression analyses adjusted for confounders such as age, duration of diabetes, body mass index, serum creatinine, HbA1c, serum albumin, log(alanine transaminase), and log(C-reactive protein) showed that serum DPP-4 was positively associated with bone formation markers (bone-specific alkaline phosphatase and osteocalcin) as well as a bone resorption marker [tartrate-resistant acid phosphatase 5b (TRACP-5b)] (\u03b2 = 0\u00b725, P < 0\u00b701; \u03b2 = 0\u00b717, P < 0\u00b705; and \u03b2 = 0\u00b730, P < 0\u00b701, respectively), but not BMD at each site. Multivariate logistic regression analyses adjusted for the confounders described above revealed that serum DPP-4 levels were associated with the presence of multiple VFs (odds ratio 1\u00b761, 95% confidential interval 1\u00b705-2\u00b749 per SD increase, P < 0\u00b705). This association was still significant after additional adjustment for any sites of BMD or bone turnover markers except for TRACP-5b.",
            "output": [
                "Is serum dipeptidyl peptidase-4 associated with multiple vertebral fractures in type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-913f3404da8b4575b947a6a57fc17e3c",
            "input": "Hair loss is related to follicular density, programmed regrowth and hair productivity.', 'The dissatisfaction with hair growth in patients experiencing hair loss might be due to slower linear hair growth rate (LHGR).', 'LHGR and hair diameter was evaluated in Caucasian controls and patients with patterned hair loss employing the validated non-invasive, contrast-enhanced-phototrichogram with exogen collection.', 'We evaluated 59,765 anagen hairs (controls 24,609, patients 35,156) and found thinner hairs grew slower than thicker hairs. LHGR in normal women was generally higher than in normal men. LHGR correlates with hair diameter (P < 0.006) and global thinning is associated with slower growth rates. Compared with hair of equal thickness in controls, subjects affected with patterned hair loss showed reduced hair growth rates, an observation found in both male and female patients. Males with pattern hair loss showed further reduction in growth rates as clinical severity worsened. However, sample size limitations prevented statistical evaluation of LHGR in severely affected females.",
            "output": [
                "Are gender differences in scalp hair growth rates maintained but reduced in pattern hair loss compared to controls?"
            ]
        },
        {
            "id": "task847-8c7f8629898e4464be50be9f88fa2a6a",
            "input": "Neuromuscular blocking agents (NMBAs) bind the nicotinic acetylcholine receptor \u03b11 (nAChR\u03b11) that also contributes to inflammatory signaling. Thus, the author hypothesized that the use of NMBA mitigates lung injury by improving ventilator synchrony and decreasing inflammatory responses.', 'Lung injury was induced by intratracheal instillation of hydrogen chloride in rats that were randomized to receive no NMBA with evidence of asynchronous ventilation (noNMBA/aSYNC, n = 10); no NMBA with synchronous ventilation (noNMBA/SYNC, n = 10); cisatracurium (CIS, n = 10); or pancuronium (PAN, n = 10). Mechanical ventilation was set at a tidal volume of 6 ml/kg and positive end-expiratory pressure 8 cm H2O for 3 h. Human lung epithelial, endothelial, and CD14\u207a cells were challenged with mechanical stretch, lipopolysaccharide, lung lavage fluids (bronchoalveolar lavage fluid), or plasma obtained from patients (n = 5) with acute respiratory distress syndrome, in the presence or absence of CIS or small-interfering RNA and small hairpin RNA to attenuate the cell expression of nAChR\u03b11.', 'The use of CIS and PAN improved respiratory compliance (7.2 \u00b1 0.7 in noNMBA/aSYNC, 6.6 \u00b1 0.5 in noNMBA/SYNC, 5.9 \u00b1 0.3 in CIS, and 5.8 \u00b1 0.4 cm H2O/l in PAN; P < 0.05), increased PaO2 (140 \u00b1 54, 209 \u00b1 46, 269 \u00b1 31, and 269 \u00b1 54 mmHg, respectively, P < 0.05), and decreased the plasma levels of tumor necrosis factor-\u03b1 (509 \u00b1 252 in noNMBA, 200 \u00b1 74 in CIS, and 175 \u00b1 84 pg/ml in PAN; P < 0.05) and interleukin-6 (5789 \u00b1 79, 1608 \u00b1 534, and 2290 \u00b1 315 pg/ml, respectively; P < 0.05). The use of CIS and PAN or silencing the receptor nAChR\u03b11 resulted in decreased cytokine release in the human cells in response to a variety of stimuli mentioned earlier.",
            "output": [
                "Does neuromuscular Blocking Agent Cisatracurium attenuate Lung Injury by Inhibition of Nicotinic Acetylcholine Receptor-\u03b11?"
            ]
        },
        {
            "id": "task847-e080dffcd77d46819d26f566bcbc0694",
            "input": "Temozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35\\xa0\u03bcM).', 'MGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500\\xa0\u03bcM. Clonogenic GSC surviving 500\\xa0\u03bcM TMZ (GSC-500\\xa0\u03bcM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC.', 'The molecular signatures characterized an activation of protective stress responses in GSC-500\\xa0\u03bcM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500\\xa0\u03bcM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500\\xa0\u03bcM TMZ and GSC-parental to 35\\xa0\u03bcM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p\\u2009=\\u20090.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p\\u2009=\\u20090.0489).",
            "output": [
                "Does bone morphogenetic protein 7 sensitize O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide?"
            ]
        },
        {
            "id": "task847-5aaf9a9910fb4a019e860888e1ed9719",
            "input": "Osteoarthritis (OA) is a multifactorial disease, and recent studies have suggested that cell cycle-related proteins play a role in OA pathology. p21 was initially identified as a potent inhibitor of cell cycle progression. However, it has been proposed that p21 is a regulator of transcription factor activity. In this study, we evaluated the role of p21 in response to biomechanical stress.', 'Human chondrocytes were treated with p21-specific small interfering RNA (siRNA), and cyclic tensile strain was introduced in the presence or absence of a signal transducer and activator of transcription 3 (STAT3)-specific inhibitor. Further, we developed an in vivo OA model in a p21-knockout background for in vivo experiments.', 'The expression of matrix metalloproteinase (MMP13) mRNA increased in response to cyclic tensile strain following transfection with p21 siRNA, whereas the expression of aggrecan was decreased. Phospho-STAT3 and MMP-13 protein levels increased following downregulation of p21, and this was reversed by treatment with a STAT3 inhibitor. p21-deficient mice were susceptible to OA, and this was associated with increased STAT3 phosphorylation, elevated MMP-13 expression, and elevation of synovial inflammation. The expression of p21 mRNA was decreased and phosphorylation of STAT3 was elevated in human OA chondrocytes.",
            "output": [
                "Is p21 deficiency susceptible to osteoarthritis through STAT3 phosphorylation?"
            ]
        },
        {
            "id": "task847-ad92fca5d7f9468e88ac3a706ef7466e",
            "input": "Ischemic ophthalmopathy threatens people's lives and health. The herbal compound medication, Naoshuantong capsule, plays a critical role in the treatment of cardiac-cerebral vascular diseases; however, the roles and mechanisms of action of Naoshuantong capsule in ischemic ophthalmopathy is unknown. The objective of the present study was to determine the effect and mechanism of action of Naoshuantong capsule on ischemic ophthalmopathy in rats.\", 'In this study a rat model of ischemic ophthalmopathy was constructed using a high intra-ocular pressure-induced ischemia/reperfusion model. The effects of Naoshuantong capsule on ischemic ophthalmopathy were detected using electroretinography, and changes in retinal ultrastructure were examined by HE staining and electron microscopy. The mechanism of action of Naoshuantong capsule on ischemic ophthalmopathy was explored by immunofluorescence and real-time PCR.', 'Rat models of ischemic ophthalmopathy were successfully constructed by intra-ocular hypertension, which presented decreased amplitudes of the electroretinogram (ERG-b) wave and total retinal thickness, intracellular damage, increased expression of Bax and caspase 3, and decreased expression of Bcl-2. Treatment with Naoshuantong capsule attenuated the changes and damage to the ischemic retina in the rat model, inhibited the over-expression of Bax and caspase 3, and increased the expression of Bcl-2.",
            "output": [
                "Does herbal compound Naoshuantong capsule attenuate retinal injury in ischemia/reperfusion rat model by inhibiting apoptosis?"
            ]
        },
        {
            "id": "task847-dbd03325fa3945be89c830eeb4e51215",
            "input": "Embryonic lethality is a recognized phenotypic expression of individual gene mutations in model organisms. However, identifying embryonic lethal genes in humans is challenging, especially when the phenotype is manifested at the preimplantation stage.', 'In an ongoing effort to exploit the highly consanguineous nature of the Saudi population to catalog recessively acting embryonic lethal genes in humans, we have identified two families with a female-limited infertility phenotype. Using autozygosity mapping and whole exome sequencing, we map this phenotype to a single mutation in TLE6, a maternal effect gene that encodes a member of the subcortical maternal complex in mammalian oocytes. Consistent with the published phenotype of mouse Tle6 mutants, embryos from female patients who are homozygous for the TLE6 mutation fail to undergo early cleavage, with resulting sterility. The human mutation abrogates TLE6 phosphorylation, a step that is reported to be critical for the PKA-mediated progression of oocyte meiosis II. Furthermore, the TLE6 mutation impairs its binding to components of the subcortical maternal complex.",
            "output": [
                "Does tLE6 mutation cause the earliest known human embryonic lethality?"
            ]
        },
        {
            "id": "task847-b44e0dc257074bb4b15594daccd669e1",
            "input": "To avoid adverse patient outcomes from inappropriate treatment, it is recommended that an atrial electrogram (AEG) be recorded whenever atrial arrhythmias develop in patients after cardiac surgery. However, AEGs are not commonly performed because nurses lack knowledge about differentiating atrial rhythms on AEGs.', \"To investigate whether completing a novel online evidence-based education program on interpreting AEGs would improve critical care nurses' AEG interpretation.\", 'Specialized critical care nurses were taught about obtaining and interpreting atrial rhythms on AEGs using a 42-minute online mini-movie. AEG interpretation was assessed pre and two and eight weeks post-intervention.', 'AEG interpretation increased two weeks post intervention and was retained at eight weeks. Some participants used this newly acquired knowledge to interpret arrhythmias that were not taught during the education program.",
            "output": [
                "Does atrial electrogram interpretation improve after an innovative education program?"
            ]
        },
        {
            "id": "task847-5599be5145b14f1880df2ac142f8af51",
            "input": "To investigate the effect of treatment with ivacaftor on insulin secretion in patients with cystic fibrosis (CF) (\u0394F508\\\\S549R) having CFRD/impaired insulin secretion.', 'A standard OGTT was performed before and after 16weeks of treatment with ivacaftor in 2 sibling patients with CF carrying the S549R gating mutation. The area under the curve (AUC) for glucose and insulin was calculated using the trapezoidal estimation.', 'Before treatment, the OGTT of case 1 showed indeterminate glycemia; the OGTT of case 2 indicated CFRD. After ivacaftor treatment the OGTT demonstrated improved insulin secretion pattern mainly by increased first phase early insulin secretion, resulting in reduction of the AUC of glucose in both cases.",
            "output": [
                "Does cFTR potentiator therapy ameliorate impaired insulin secretion in CF patients with a gating mutation?"
            ]
        },
        {
            "id": "task847-2ee88bb7b0084855ad3a7cd4f1508e24",
            "input": "To explore the effects of methylglyoxal on endothelia cell migration.', 'Human umbilical vein endothelial cells (HUVECs) were stimulated by serial concentrations of methylglyoxal (MGO, 0, 25, 50, 100 and 200 \u00b5mol/L) for 24 h, and the cell migration was assessed by scratch wound and Transwell assay. The expression of integrin \u03b23 in the treated cells was examined by immunoblotting, and the effect of an anti-\u03b23 antibody, LM609, on cell migration was investigated.', 'Methylglyoxal significantly inhibited HUVEC migration in a concentration-dependent manner (P<0.05). Methylglyoxal decreased the expression of integrin \u03b23 in a time- and concentration-dependent manner (P<0.05). LM609 also significantly inhibited HUVEC migration (P<0.05).",
            "output": [
                "Does [ Methylglyoxal inhibit human umbilical vein cell migration in vitro by down-regulating integrin\u03b23 ]?"
            ]
        },
        {
            "id": "task847-4d934b856ab94849b639d4b6a1290cd5",
            "input": "There is well-known inter-individual variability in the cholesterol-lowering effect of statins. However, inter-individual variability in response to rosuvastatin treatment in subjects with hypercholesterolemia has not been clearly established. This study aimed to evaluate the associations of CYP2C9 genetic polymorphism with the efficacy and safety of rosuvastatin in Chinese patients with hyperlipidemia.', 'A total of 218 patients with hyperlipidemia were selected and treated with 10 mg rosuvastatin per day for 12 weeks. Blood samples were collected prior to the treatment and after 4, 8, and 12 weeks of treatment. Clinical biochemistry analyses for serum lipid profiles were performed. Genotyping for CYP2C9 polymorphisms was performed using allele-specific real-time PCR.', '197 out of 218 patients featured a wild-type CYP2C9*1/*1 genotype, and 21 patients featured a CYP2C9*1/*3 or CYP2C9*3/*3 mutation genotype. No patients with CYP2C9*2 alleles were identified. Sixteen patients discontinued the medication due to adverse effects. No serious adverse events (i.e., hepatotoxicity or myolysis) were observed. After the 12 weeks of treatment, we observed significant reductions in total cholesterol (TC), triglycerides and low-density lipoprotein (LDL) levels compared to baseline (p < 0.05). Patients with the mutant genotype showed a higher TC-lowering and LDL-lowing effect compared to those with wild-type genotypes (TC: 45.05% vs. 38.96%, p = 0.041; LDL: 44.97% vs. 39.28%, p = 0.029). The frequency of adverse drug reactions in the studied patients did not differ by CYP2C9 genotypes (p > 0.05).",
            "output": [
                "Is cYP2C9 Genetic Polymorphism a Potential Predictive Marker for the Efficacy of Rosuvastatin Therapy?"
            ]
        },
        {
            "id": "task847-44755da596e54d4eb1b7ad7d3f11947f",
            "input": "The relationship between microRNA-1 (miR-1) expression and prognosis has not been reported in hepatocellular carcinoma (HCC). The present study aimed to explore the clinicopathological significance and the prognostic role of miR-1 in HCC.', 'The expression levels of miR-1 were quantified using real-time quantitative PCR (q-PCR) in 40 surgically resected HCC samples and matched adjacent non-cancerous tissues.', 'MiR-1 expression was significantly downregulated in HCC compared with matched non-cancerous tissues. Aberrant miR-1 expression was significantly correlated with gender, expression of hepatitis B virus surface antigen (HBsAg), tumor differentiation, vein invasion, and TNM stage. Patients with low expression of miR-1 had significantly reduced overall survival compared with patients with high expression of miR-1 (p = 0.04).The multivariate Cox regression analysis indicated that miR-1 expression (HR = 2.79; p = 0.005), gender (HR = 0.087; p = 0.005), vein invasion (HR = 0.172; p = 0.007), and TNM stage (HR = 3.421; p = 0.001) were independent prognostic factors for overall survival.",
            "output": [
                "Is downregulation of MicroRNA-1 Associated with Poor Prognosis in Hepatocellular Carcinoma?"
            ]
        },
        {
            "id": "task847-44e8a70db42a4f36b7929dc964d28b11",
            "input": "Endoscopic removal of duodenal and colorectal adenomas is currently considered to be the standard of care for prevention of adenocarcinoma. The use of cautery carries a risk of delayed bleeding, post-polypectomy syndrome, and perforation. We examined the safety and feasibility of removing colonic and duodenal polyps \u2265\\u200a1\\u200acm using a piecemeal cold snare polypectomy technique.', 'The study included 15 patients with duodenal polyps \u2265\\u200a1\\u200acm and 15 patients with colonic polyps \u2265\\u200a1\\u200acm.', 'Bleeding, perforation, abdominal pain, or hospitalization occurring within 2 weeks of polypectomy.', 'Between 24 August 2011 and 29 April 2013, 15 patients had removal of duodenal polyps \u2265\\u200a1\\u200acm. Mean patient age was 64 years and 9/15 patients were male. The mean polyp size was 24\\u200amm (10\\u200a-\\u200a60\\u200amm). All polyps were removed with a cold snare and some required cold biopsy forceps. One patient required hospitalization for gastrointestinal blood loss 7 days post-polypectomy; this patient was using Coumadin. Between 27 February 2012 and 30 May 2013, 15 patients underwent resection of a \u2265\\u200a1\\u200acm colonic polyp.\\u200aMean patient age was 68 years and 9/15 were male. The mean polyp size was 20\\u200amm (10\\u200a-\\u200a45\\u200amm). All polyps were primarily removed with a cold snare. None of the patients required hemostatic clips for control of immediate bleeding. One patient presented to the emergency department with abdominal pain 1 day after initial endoscopy. CT scan showed no abnormalities and the patient was discharged.",
            "output": [
                "Do cold snare piecemeal resection of colonic and duodenal polyps \u22651 cm?"
            ]
        },
        {
            "id": "task847-8ec6ec060ea449d1b9d3c906757bd895",
            "input": "To assessdoctor's knowledge on the relevance of the problem of sleep disorders, methods of their diagnosis and treatment.\", 'The survey was conducted among90physicians of different the rapeuticspecialties of Kazan medical institutions.', 'The doctors believe that main causes of sleep disorders are stressors (20%), depression (13%), neurosis (13%), chronic diseases (13%), asthenia (10%), pain (10%). An analysis of treatment prescribed to patients with sleep disorders revealed large differences.",
            "output": [
                "Do [ What do the doctors of different specialties know about sleep disorders and their treatment ]?"
            ]
        },
        {
            "id": "task847-4f641f19bd25458c89ee95482d8bb438",
            "input": "The heart requires constant sources of energy mostly from free fatty acids (FFA) and glucose. The alteration in myocardial substrate metabolism occurs in the heart of diabetic patients, but its specific association with other metabolic variables remains unclear. We aimed to evaluate glucose uptake in hearts of subjects with normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) using [(18)F]-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) in association with visceral and subcutaneous adiposity, and metabolic laboratory parameters.', 'A total of 346 individuals (NGT, n = 76; prediabetes, n = 208; T2DM, n = 62) in a health promotion center of a tertiary hospital were enrolled. The fasting myocardial glucose uptake, and visceral and subcutaneous fat areas were evaluated using (18)FDG-PET and abdominal computed tomography, respectively.', 'Myocardial glucose uptake was significantly decreased in subjects with T2DM compared to the NGT or prediabetes groups (p for trend = 0.001). Multivariate linear regression analyses revealed that visceral fat area (\u03b2 = -0.22, p = 0.018), fasting FFA (\u03b2 = -0.39, p < 0.001), and uric acid levels (\u03b2 = -0.21, p = 0.007) were independent determinants of myocardial glucose uptake. Multiple logistic analyses demonstrated that decreased myocardial glucose uptake (OR 2.32; 95% CI 1.02-5.29, p = 0.045) and visceral fat area (OR 1.02, 95% CI 1.01-1.03, p = 0.018) were associated with T2DM.",
            "output": [
                "Is visceral adiposity associated with altered myocardial glucose uptake measured by ( 18 ) FDG-PET in 346 subjects with normal glucose tolerance , prediabetes , and type 2 diabetes?"
            ]
        },
        {
            "id": "task847-c906c5976bdc4f7e88829bb820724d97",
            "input": "Previous studies have shown that Fructus Ligustri Lucide (FLL) can be used to anti-cancer. However, the mechanism by which FLL mediate this effect is unclear. In the present study, aqueous extracts of FLL induced cell apoptosis in human gastric carcinoma cell was investigated.', 'The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining and hoechst 33342 staining. The protein expression of cell cycle regulators and tumor suppressors were analyzed by western blotting.', 'Treatment of human gastric carcinoma cells with FLL induced cell death in a dose- and time-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that the proportion of the early and terminal phase of apoptosis cells had gained after FLL treatment as compared to untreated group. Moreover, human gastric carcinoma cells were exposed to the aqueous extracts of FLL for 48 h, which resulted in an accumulation of cells in G2/M phase. Apoptotic bodies were clearly observed in human gastric carcinoma that had been treated with FLL for 48 h and then stained with Hochest 33342. Treatment of gastric carcinoma cells with increasing doses of FLL and increasing durations significantly increased the protein expression of Bax and Caspase3, decreased the anti-apoptotic Bcl-2 level. The expression of CDC2 and cdc25C were downregulated upon FLL treatment in human gastric carcinoma. In contrast, p53 and p21 were obviously upregulated by FLL treatment in a concentration-dependent manner.",
            "output": [
                "Do aqueous extracts of Fructus Ligustri Lucide induce gastric carcinoma cell apoptosis and G2/M cycle arrest?"
            ]
        },
        {
            "id": "task847-dfae34517eec46d09911508d142f827c",
            "input": "To evaluate the relationship between susceptibility to proactive semantic interference (PSI) and retroactive semantic interference (RSI) and brain amyloid load in non-demented elders.', '27 participants (11 cognitively normal [CN] with subjective memory complaints, 8 CN without memory complaints, and 8 with mild cognitive impairment [MCI]) underwent complete neurological and neuropsychological evaluations. Participants also received the Semantic Interference Test (SIT) and AV-45 amyloid PET imaging.', 'High levels of association were present between total amyloid load, regional amyloid levels, and the PSI measure (in the entire sample and a subsample excluding MCI subjects). RSI and other memory measures showed much weaker associations or no associations with total and regional amyloid load. No associations between amyloid levels and non-memory performance were observed.",
            "output": [
                "Is proactive Semantic Interference Associated with Total and Regional Abnormal Amyloid Load in Non-Demented Community-Dwelling Elders : A Preliminary Study?"
            ]
        },
        {
            "id": "task847-b4ca85c427064d73bacf30b435916764",
            "input": "Several viruses have been recently isolated from Mediterranean phlebotomine sand flies; some are known to cause human disease while some are new to science. To monitor the Phlebotomus-borne viruses spreading, field studies are in progress using different sand fly collection and storage methods. Two main sampling techniques consist of CDC light traps, an attraction method allowing collection of live insects in which the virus is presumed to be fairly preserved, and sticky traps, an interception method suitable to collect dead specimens in high numbers, with a risk for virus viability or integrity. Sand flies storage requires a \"deep cold chain\" or specimen preservation in ethanol. In the present study the influence of sand fly collection and storage methods on viral isolation and RNA detection performances was evaluated experimentally.', 'Specimens of laboratory-reared Phlebotomus perniciosus were artificially fed with blood containing Toscana virus (family Bunyaviridae, genus Phlebovirus). Various collection and storage conditions of blood-fed females were evaluated to mimic field procedures using single and pool samples. Isolation on VERO cell cultures, quantitative Real time-Retro-transcriptase (RT)-PCR and Nested-RT-PCR were performed according to techniques commonly used in surveillance studies.', 'Live engorged sand flies stored immediately at -80 \u00b0C were the most suitable sample for phlebovirus identification by both virus isolation and RNA detection. The viral isolation rate remained very high (26/28) for single dead engorged females frozen after 1 day, while it was moderate (10/30) for specimens collected by sticky traps maintained up to 3 days at room temperature and then stored frozen without ethanol. Opposed to viral isolation, molecular RNA detection kept very high on dead sand flies collected by sticky traps when left at room temperature up to 6 days post blood meal and then stored frozen in presence (88/95) or absence (87/88) of ethanol. Data were confirmed using sand fly pools.",
            "output": [
                "Do experimental evaluation of sand fly collection and storage methods for the isolation and molecular detection of Phlebotomus-borne viruses?"
            ]
        },
        {
            "id": "task847-f775e657dc2b4dfdbedcfc53c4fcace0",
            "input": "Diabetic nephropathy (DN) is a serious complication that commonly confronted by diabetic patients. A common theory for the pathogenesis of this renal dysfunction in diabetes is cell injury, inflammation as well as oxidative stress. In this content, the detailed molecular mechanism underlying high glucose induced renal tubular epithelial injury was elaborated.', \"An in vivo rat model of diabetes by injecting streptozotocin (STZ) and an in vitro high glucose incubated renal tubular epithelial cell (HK-2) model were used. Expression levels of Keap1, nuclear Nrf2 and p65 were determined by western blotting. Level of microR-29 (miR-29) was assessed using quantitative RT-PCR. Combination of p65 and miR-29 promotor was assessed using chromatin immunoprecipitation. Keap1 3'-UTR activity was detected using luciferase reporter gene assay. Cell viability was determined using MTT assay.\", 'In diabetic rat, miR-29 was downregulated and its expression is negatively correlated with both of serum creatinine and creatinine clearance. In high glucose incubated HK-2 cell, deacetylases activity of Sirt1 was attenuated that leads to decreased activity of nuclear factor kappa B (NF-\u03baB). NF-\u03baB was demonstrated to regulate miR-29 expression by directly binding to its promotor. The data of luciferase assay showed that miR-29 directly targets to Keap1 mRNA. While high glucose induced down regulation of miR-29 contributed to enhancement of Keap1 expression that finally reduced Nrf2 content by ubiquitinating Nrf2. Additionally, overexpression of miR-29 effectively relieved high glucose-reduced cell viability.",
            "output": [
                "Does high glucose induce renal tubular epithelial injury via Sirt1/NF-kappaB/microR-29/Keap1 signal pathway?"
            ]
        },
        {
            "id": "task847-8d2b48dc5b2e4dc48df8594cb9b1b5e3",
            "input": "Although prevalent in prokaryotes, horizontal gene transfer (HGT) is rarer in multicellular eukaryotes. Bdelloid rotifers are microscopic animals that contain a higher proportion of horizontally transferred, non-metazoan genes in their genomes than typical of animals. It has been hypothesized that bdelloids incorporate foreign DNA when they repair their chromosomes following double-strand breaks caused by desiccation. HGT might thereby contribute to species divergence and adaptation, as in prokaryotes. If so, we expect that species should differ in their complement of foreign genes, rather than sharing the same set of foreign genes inherited from a common ancestor. Furthermore, there should be more foreign genes in species that desiccate more frequently. We tested these hypotheses by surveying HGT in four congeneric species of bdelloids from different habitats: two from permanent aquatic habitats and two from temporary aquatic habitats that desiccate regularly.', 'Transcriptomes of all four species contain many genes with a closer match to non-metazoan genes than to metazoan genes. Whole genome sequencing of one species confirmed the presence of these foreign genes in the genome. Nearly half of foreign genes are shared between all four species and an outgroup from another family, but many hundreds are unique to particular species, which indicates that HGT is ongoing. Using a dated phylogeny, we estimate an average of 12.8 gains versus 2.0 losses of foreign genes per million years. Consistent with the desiccation hypothesis, the level of HGT is higher in the species that experience regular desiccation events than those that do not. However, HGT still contributed hundreds of foreign genes to the species from permanently aquatic habitats. Foreign genes were mainly enzymes with various annotated functions that include catabolism of complex polysaccharides and stress responses. We found evidence of differential loss of ancestral foreign genes previously associated with desiccation protection in the two non-desiccating species.",
            "output": [
                "Is horizontal gene transfer in bdelloid rotifers ancient , ongoing and more frequent in species from desiccating habitats?"
            ]
        },
        {
            "id": "task847-19f2a255c91d46cf8d0568e865a57715",
            "input": "Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone.', 'Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014.', 'Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis.",
            "output": [
                "Does low-Dose Docetaxel Combined with Dexamethasone be Feasible for Patients with Castration-Resistant Prostate Cancer?"
            ]
        },
        {
            "id": "task847-a6764a1ccec748ffaf088ff4cb96b972",
            "input": "Platelets promote liver regeneration through site-specific serotonin release from dense granules, triggering proliferative signaling in hepatocytes. However, the effects of factors derived from platelet \u03b1-granules on liver regeneration are unclear, because \u03b1-granules contain bioactive molecules with opposing functions. Because \u03b1-granule molecules are stored in separate compartments, it has been suggested that platelets selectively release their \u03b1-granule content dependent on the environmental stimulus. Therefore, we investigated the pattern of circulating \u03b1-granule molecules during liver regeneration in 157 patients undergoing partial hepatectomy. We measured plasma levels of \u03b1-granule-derived factors in the liver vein at the end of liver resection, as well as on the first postoperative day. We observed a rapid accumulation of platelets within the liver after induction of liver regeneration. Platelet count and P-selectin (a ubiquitous cargo of \u03b1-granules) were not associated with postoperative liver dysfunction. However, low plasma levels of vascular endothelial growth factor (VEGF), but high levels of thrombospondin 1 (TSP-1), predicted liver dysfunction after resection. Patients with an unfavorable postoperative \u03b1-granule release profile (high TSP-1/low VEGF) showed substantially worse postoperative clinical outcomes. The unfavorable postoperative \u03b1-granule release profile was associated with increased postoperative portal venous pressure and von Willebrand factor antigen levels as a marker for intrahepatic endothelial dysfunction.",
            "output": [
                "Does the profile of platelet \u03b1-granule released molecules affect postoperative liver regeneration?"
            ]
        },
        {
            "id": "task847-0e4aa5dcc8f446c1b8b799638cbcc402",
            "input": "Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS.', 'We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low-ADC lesions and 2 post-bevacizumab scans \u226490 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P = .05.', 'Median OS was 9.1 months (95% CI = 7.2-14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm(3)) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003-1.025], P = .009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P = .08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P > .51). Also correlated with shorter OS were the pre-bevacizumab nonenhancing volume (P = .025), the first post-bevacizumab enhancing volume (P = .040), and the second post-bevacizumab enhancing volume (P = .004).",
            "output": [
                "Do large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients?"
            ]
        },
        {
            "id": "task847-816c2e857f1f4bffb2bb04a444298835",
            "input": "Glucose-transporter-1 (Glut-1) may be a useful marker for differentiating B3 thymomas and thymic carcinomas. Since the literature is limited, we undertook a study to evaluate its diagnostic value in a series of thymic epithelial tumors.', 'Glut-1 expression was studied by the group of pathologists linked to the French national oncological network RYTHMIC. Immunostaining was performed on a whole section of one paraffin block in a series of 92 successive surgical specimens. Patterns (focal, zonal, diffuse) and intensity of Glut-1 expression were assessed and compared with WHO histological subtypes.', 'Expression was mainly restricted to epithelial cells. Immature T-lymphocytes were negative. A diffuse, moderate or strong staining was observed in most thymic carcinomas (15/16). In B3 thymomas (10/11) and in B3 thymomas borderline to thymic carcinomas (5/6), a moderate to strong zonal staining was observed at distance from vessels and fibrous septa. This pattern sometimes created the aspect of an anastomosing network in large cellular lobules. In B1 thymomas, immunostaining highlighted foci of medullary differentiation (7/8). B2 thymomas (n=25) were heterogeneous, with a spectrum of patterns ranging between those of B1 and B3 thymomas. Type A thymomas (n=5) mostly presented a weak positivity but one aggressive case showed zonal moderate/strong positivity. Most AB thymomas (15/17) showed weak to moderate immunostaining in spindle cell areas. In micronodular thymomas (n=3), epithelial cells and B-lymphocytes were weakly positive while follicular dendritic cells were strongly highlighted. One metaplastic thymoma displayed diffuse and moderate positivity.",
            "output": [
                "Are glut-1 intensity and pattern of expression in thymic epithelial tumors predictive of WHO subtypes?"
            ]
        },
        {
            "id": "task847-f8fe68773e4243418b9a9c816a557b76",
            "input": "Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD(+) biosynthesis from nicotinamide, is one of the major factors regulating cancer cells metabolism and is considered a promising target for treating cancer. The prototypical NAMPT inhibitor FK866 effectively lowers NAD(+) levels in cancer cells, reducing the activity of NAD(+)-dependent enzymes, lowering intracellular ATP, and promoting cell death.', \"We show that FK866 induces a translational arrest in leukemia cells through inhibition of MTOR/4EBP1 signaling and of the initiation factors EIF4E and EIF2A. Specifically, treatment with FK866 is shown to induce 5'AMP-activated protein kinase (AMPK) activation, which, together with EIF2A phosphorylation, is responsible for the inhibition of protein synthesis. Notably, such an effect was also observed in patients' derived primary leukemia cells including T-cell Acute Lymphoblastic Leukemia. Jurkat cells in which AMPK or LKB1 expression was silenced or in which a non-phosphorylatable EIF2A mutant was ectopically expressed showed enhanced sensitivity to the NAMPT inhibitor, confirming a key role for the LKB1-AMPK-EIF2A axis in cell fate determination in response to energetic stress via NAD(+) depletion.",
            "output": [
                "Does eIF2A-dependent translational arrest protect leukemia cells from the energetic stress induced by NAMPT inhibition?"
            ]
        },
        {
            "id": "task847-c98f3606d4d4414aaf7db6aa0c509c5e",
            "input": "High anxiety has been reported in patients with drug hypersensitivity reaction (DHR); however, its relationship with the test results was not studied previously.', 'We aimed to investigate the association of patient anxiety with the results of drug tests together with the other contributing factors.', 'Sixty-seven patients were included in the study between November 2012 and April 2013, in whom drug tests were performed after clinical evaluation and application of the Penn State Worry Questionnaire (PSWQ).', 'The mean \u00b1 standard deviation (SD) age was 43.5 \u00b1 12.9 years, and 73.1% of the patients were females. The patient group had significantly higher mean \u00b1 SD PSWQ score than 35 control subjects without histories of DHRs and major psychiatric disorders (47.95 \u00b1 14.64 versus 40.22 \u00b1 11.86, p = 0.008). However, the mean \u00b1 SD. PSWQ score of the patients with positive drug test results was not significantly different from the patients with negative drug test results (46.06 \u00b1 13.41 versus 50.47 \u00b1 18.02, p = 0.32). Panic attack symptoms were more common in the reactions with positive test results than in the reactions with negative test results (74.0% versus 48.9%, p = 0.01). However, presence of panic attack symptoms [odds ratio (OR): 1.25, 95% confidence interval (CI): 0.44-3.54; p = 0.67] was not found independently associated with positive test results in the multiple logistic regression model.",
            "output": [
                "Does evaluation of anxiety levels and factors associated with positive test result in patients with drug hypersensitivity?"
            ]
        },
        {
            "id": "task847-64f5be1da4ef48adb62248fba3976979",
            "input": "Cross-sectional, clinical measurement.', 'To investigate the validity of the Duru\u00f6z Hand Index (DHI) in the assessment of hand function in patients with tetraplegia.', \"A total of 40 patients with tetraplegia participated. Patients' upper extremities were assessed on the level of 'body function and structure' [The American Spinal Cord Injury Association (ASIA) Impairment Scale (AIS) 2000 revised criteria, upper extremity motor score (UEMS), neurologic level of injury and visual analogue scale of hand function (VAS-HF)], 'activity' [DHI and Quadriplegia index of function-short form (QIF-SF)] and 'body function and structure, activity and participation' [Health Survey Short Form-36 (SF-36)] according to International Classification of Function.\", 'The DHI showed significant correlations with UEMS, AIS, QIF-SF, VAS-HF, physical functioning and physical compound summary scores of SF-36.",
            "output": [
                "Do validation of Duru\u00f6z Hand Index in patients with tetraplegia?"
            ]
        },
        {
            "id": "task847-6ef03adbd2614a64a7a2ce3e3d1c80c3",
            "input": "Transplanted cell survival might greatly improve the therapeutic efficacy of cell therapy. Diazoxide (DZ), a highly selective mitochondrial ATP-sensitive potassium channel opener, is known to suppress cell apoptosis and protect cells in oxidative stressed ischemic environment. We explored the mechanisms involved in DZ pre-treatment-induced anti-apoptotic effect on L6 skeletal myoblast (SKM).', 'L6 SKMs were divided into control group, H2O2 group, DZ\\xa0+\\xa0H2O2 group and DZ\\xa0+\\xa0LY\\xa0+\\xa0H2O2 group. Treatments of 400\\xa0\u03bcmol/L H2O2 for 24\\xa0h alone, or after 200\\xa0\u03bcmol/L DZ pre-treatment for 30\\xa0min, or after DZ and 50\\xa0\u03bcmol/L LY294002 co-administration for 30\\xa0min were performed. The cell apoptosis rates were assessed by flow cytometric analysis. The changes of mitochondrial membrane potential were determined by JC-1 mitochondrial staining. The activation of phosphatidylinositol-3 kinase (PI3K)/Akt, caspase-9 and caspase-3 was detected by western blot.', 'Compared with the H2O2 group, DZ pre-treatment protected cells from H2O2-induced damage, increased Akt phosphorylation, prevented mitochondrial membrane depolarization as well as the activation of caspase-9 and caspase-3 and decreased the cell apoptosis rate. However, the DZ-induced cytoprotective and anti-apoptosis effects were partly inhibited by co-administration of a PI3K inhibitor, LY294002.",
            "output": [
                "Does diazoxide protect L6 skeletal myoblasts from H2O2-induced apoptosis via the phosphatidylinositol-3 kinase/Akt pathway?"
            ]
        },
        {
            "id": "task847-5acedb3cd7a44fe58fb4031cdca02f08",
            "input": "Delirium is an important morbidity following heart surgery. We sought to determine whether dopamine infusion is associated with increased risk of delirium in patients undergoing coronary artery bypass grafting.', 'A total of 137 patients (mean age; 61.02\u00b17.83, 105 males) were included in the study. Patients undergoing isolated coronary artery bypass grafting were considered eligible and those with preoperative neurological deficit or significant neurocognitive disorders, dementia or psychiatric disorders were excluded. Primary outcome measure was occurrence of delirium within 72 hours after operation. The diagnosis of delirium was made using confusion assessment method for the intensive care unit questionnaire. Both administration of dopamine as a dichotomised variable and the total amount of dopamine per kg body-weight were included in two different logistic regression models.', 'Delirium occurred in 18 (13.1%) patients. Age adjusted Mantel-Haenszel relative risk for delirium with receiving dopamine was 4.62. Relative risk was 2.37 (0.18 to 31.28, 95% CI, p=0.51) in total doses over 10mg whereas it was 3.55 (1.16 to 10.89 95% CI, p=0.02) in total doses over 30 mg per kg body-weight. Older age (p=0.03), dopamine administration (OR: 9.227 95% CI, 2.688-32.022, p<0.001) and the amount of dopamine administered (OR: 1.072, 95% CI, 1.032-1.115, p<0.001) were independent predictors for delirium 72 hours after surgery.",
            "output": [
                "Is dopamine Administration a Risk Factor for Delirium in Patients Undergoing Coronary Artery Bypass Surgery?"
            ]
        },
        {
            "id": "task847-e9f0fe9fa251412bb921d08ffb8f0e35",
            "input": "Intestinal fibrosis is mainly associated with Crohn's disease and is defined as a progressive and excessive deposition of extracellular matrix components. No specific antifibrotic therapies are available. In this study, we evaluate the antifibrotic effect of a novel 5-ASA analog able to activate the peroxisome proliferator-activated receptor \u03b3, named GED-0507-34 Levo.\", 'Colonic fibrosis was induced in 110 C57BL/6 mice by 3 cycles of 2.5% (wt/vol) dextran sulfate sodium administration for 6 weeks. The preventive effects of oral daily GED (30 mg \u00b7 kg(-1) \u00b7 d(-1)) administration were evaluated using a macroscopic and histological score and also through biological endpoints. Expression of main markers of myofibroblasts activation was determined in transforming growth factor (TGF-\u03b2)-stimulated intestinal fibroblasts and epithelial cells.', 'GED improved macroscopic and microscopic intestinal lesions in dextran sulfate sodium-treated animals and reduced the profibrotic gene expression of Acta2, COL1a1, and Fn1 by 1.48-folds (P < 0.05), 1.93-folds (P < 0.005), and 1.03-fold (P < 0.05), respectively. It reduced protein levels of main markers of fibrosis (\u03b1-SMA and Collagen I-II) and the main TGF-\u03b2/Smad pathway components. GED also decreased the interleukin-13 and connective tissue growth factor expression by 1.89-folds (P < 0.05) and 2.2-folds (P < 0.005), respectively. GED inhibited TGF-\u03b2-induced activation of both fibroblast and intestinal epithelial cell lines, by regulating mRNA expression of \u03b1-SMA and fibronectin, and restoring the TGF-\u03b2-induced loss of intestinal epithelial cell markers. GED treatment also reduced the TGF-\u03b2 and ACTA1 expression in primary human intestinal fibroblasts from ulcerative colitis patients.",
            "output": [
                "Does novel PPAR\u03b3 Modulator GED-0507-34 Levo ameliorate Inflammation-driven Intestinal Fibrosis?"
            ]
        },
        {
            "id": "task847-3bb94203b33e42e49fc3dbc9b4a97526",
            "input": "Flightless I (FLII), member of the gelsolin superfamily of actin-remodeling proteins, functions as a transcriptional coregulator. We aim to evaluate a tumor-suppressive function of FLII in regulating androgen receptor (AR) in prostate cancer progression.', 'We examined FLII protein and mRNA expression in clinical prostate cancer specimens by immunohistochemistry. Kaplan-Meier analysis was conducted to evaluate the difference in disease-overall survival associated with the expression levels of FLII and AR. Prostate cancer cells stably expressing FLII or shRNA knockdown were used for functional analyses. Immunoprecipitation, Luciferase reporter, and immunofluorescence staining assays were performed to examine the functional interaction between FLII and AR.', 'Our analysis of the expression levels of FLII in a clinical gene expression array dataset showed that the expression of FLII was positively correlated with the overall survival of prostate cancer patients exhibiting high levels of AR expression. Examination of protein and mRNA levels of FLII showed a significant decrease of FLII expression in human prostate cancers. AR and FLII formed a complex in a ligand-dependent manner through the ligand-binding domain (LBD) of AR. Subsequently, we observed a competitive binding to AR between FLII and the ligand. FLII inhibited AR transactivation and decreased AR nuclear localization. Furthermore, FLII contributed to castration-sensitive and castration-resistant prostate cancer cell growth through AR-dependent signaling, and reintroduction of FLII in prostate cancer cells sensitized the cells to bicalutamide and enzalutamide treatment.",
            "output": [
                "Does flightless I Homolog repress Prostate Cancer Progression through Targeting Androgen Receptor Signaling?"
            ]
        },
        {
            "id": "task847-d5d3372ac0204567bdbe30ff8f22abfc",
            "input": "The onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma.', 'Here we studied the potential utility of miR-221/222 inhibition in sensitizing refractory multiple myeloma cells to melphalan.', 'miR-221/222 expression inversely correlated with melphalan sensitivity of multiple myeloma cells. Inhibition of miR-221/222 overcame melphalan resistance and triggered apoptosis of multiple myeloma cells in vitro, in the presence or absence of human bone marrow (BM) stromal cells. Decreased multiple myeloma cell growth induced by inhibition of miR-221/222 plus melphalan was associated with a marked upregulation of pro-apoptotic BBC3/PUMA protein, a miR-221/222 target, as well as with modulation of drug influx-efflux transporters SLC7A5/LAT1 and the ABC transporter ABCC1/MRP1. Finally, in vivo treatment of SCID/NOD mice bearing human melphalan-refractory multiple myeloma xenografts with systemic locked nucleic acid (LNA) inhibitors of miR-221 (LNA-i-miR-221) plus melphalan overcame drug resistance, evidenced by growth inhibition with significant antitumor effects together with modulation of PUMA and ABCC1 in tumors retrieved from treated mice.",
            "output": [
                "Does a 13 mer LNA-i-miR-221 Inhibitor restore Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells?"
            ]
        },
        {
            "id": "task847-a71e90b235d84acfb2ccfb51f4dda941",
            "input": "CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling.', 'CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 \u00b1 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 \u00b1 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 \u00b1 4.5 ng/ml, no CAD: 12.5 \u00b1 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD.",
            "output": [
                "Are cXCL4 Plasma Levels Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology?"
            ]
        },
        {
            "id": "task847-f63699fb1d8a46308d7f6e77d6522718",
            "input": "Despite growing evidence on the important role of micronutrients in prognosis of heart failure (HF), there has been limited research that micronutrient deficiency predicts health outcomes in patients with HF.', 'The aim of this study was to determine whether micronutrient deficiency independently predicts adverse health outcomes.', 'A total of 113 consecutive outpatients with HF completed a 3-day food diary to measure intake of 15 micronutrients. The Computer Aided Nutrition Analysis Program for Professionals was used to analyze the food diaries and determine dietary micronutrient deficiencies. Patients completed the Minnesota Living With HF Questionnaire to assess health-related quality of life (HRQoL) and were followed up for 1 year to determine cardiac-related hospitalization or cardiac death. Hierarchical multiple linear regressions and Cox proportional hazard regressions were used to determine whether micronutrient deficiencies predicted health outcomes.', 'Fifty-eight patients (51%) had at least 3 micronutrient deficiencies (range, 0-14). Calcium, magnesium, and vitamin D were the most common micronutrient deficiencies. Micronutrient deficiency was independently associated with worse HRQoL (\u03b2 = .187, P = .025) in hierarchical multiple linear regression. Thirty-nine patients were hospitalized or died during 1-year follow-up because of cardiac problems. The number of micronutrient deficiencies independently predicted cardiac event-free survival (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28).",
            "output": [
                "Does micronutrient Deficiency Independently predict Adverse Health Outcomes in Patients With Heart Failure?"
            ]
        },
        {
            "id": "task847-c7ad6283a0a94de6bdc66e96eaa0ddca",
            "input": "Complications after immediate breast reconstruction pose a significant challenge to the reconstructive surgeon. Known risk factors include smoking, obesity, age, and adjuvant oncologic therapies. Less is known about the association between axillary lymph node dissection (ALND) and the development of postoperative complications.', 'We conducted a retrospective study of all patients who underwent immediate breast reconstruction after mastectomy at our institution over a 10-year period. Our outcome was an occurrence of a major complication within 90 days postoperatively. For each patient, we recorded data on demographics, smoking status, pertinent medical history, reconstruction type, adjuvant chemotherapy and radiation, tumor pathology, and whether an ALND was performed. Odds ratios (OR) were calculated to estimate the risk of a complication if an ALND was performed.', 'One hundred eighty-four women, with 270 surgically treated breasts, were identified as having mastectomy with immediate reconstruction between 2002 and 2012. Mean age was 49.4 years (range, 25-84 years). There were 71 mastectomies with ALND performed, with 22 complications, and 199 mastectomies without ALND, with 20 complications (31% complication rate vs 10%, respectively; OR, 3.84; P < 0.001). When adjusted for reconstruction type, smoking history, obesity, age, presence of invasive disease, chemotherapy, and radiation therapy, the OR for complications was 3.49 (P < 0.01). The most common complication was infection in both groups.",
            "output": [
                "Does axillary Lymph Node Dissection be a Risk Factor for Major Complications After Immediate Breast Reconstruction?"
            ]
        },
        {
            "id": "task847-9b576d4e043d46e4af87b0a6d076f49f",
            "input": "ST-segment elevation (STE) due to inferior STE myocardial infarction (STEMI) may be misdiagnosed as pericarditis. Conversely, this less life-threatening etiology of ST elevation may be confused for inferior STEMI. We sought to determine if the presence of any ST-segment depression in lead aVL would differentiate inferior STEMI from pericarditis.', 'Retrospective study of 3 populations. Cohort 1 included patients coded as inferior STEMI, cohort 2 included patients with a discharge diagnosis of pericarditis who presented with chest pain and at least 0.5 mm of ST elevation in at least 1 inferior lead. We analyzed the presenting electrocardiogram in both populations, with careful assessment of leads II, III, aVF, and aVL. In addition, we retrospectively studied a third cohort of patients with subtle inferior STEMI (<1-mm STE with occluded artery on catheterization) and assessed the sensitivity of ST depression in lead aVL for this group.', 'Of 154 inferior STEMI patients, 154 had some amount of ST depression in lead aVL (100%; confidence interval, 98%-100%). Of the 49 electrocardiograms in the pericarditis group, all 49 had some inferior STE but none had any ST-segment depression in lead aVL (specificity, 100%; confidence interval, 91%-100%). In the third cohort, there were 272 inferior MIs with coronary occlusion, of which 54 were \"subtle.\" Of these, 49 had some ST depression in lead aVL.",
            "output": [
                "Does sT depression in lead aVL differentiate inferior ST-elevation myocardial infarction from pericarditis?"
            ]
        },
        {
            "id": "task847-026638e7d6d44855aeb1b5011e7d8dec",
            "input": "In a previous study, UBiT-100\\u2009mg, (Otsuka, Spain), a commercial (13)C-urea breath test omitting citric acid pre-treatment, had a high rate of false-positive results; however, it is possible that UBiT detected low-density 'occult' infection missed by other routine reference tests. We aimed to validate previous results in a new cohort and to rule out the possibility that false-positive UBiT were due to an 'occult' infection missed by reference tests.\", \"Dyspeptic patients (n = 272) were prospectively enrolled and UBiT was performed, according to the manufacturer's recommendations. Helicobacter pylori infection was determined by combining culture, histology and rapid urease test results. We calculated UBiT sensitivity, specificity, positive and negative predictive values (with 95% CI). In addition, we evaluated 'occult' H. pylori infection using two previously-validated polymerase chain reaction (PCR) methods for urease A (UreA) and 16\\u2009S sequences in gastric biopsies. We included 44 patients with a false-positive UBiT, and two control groups of 25 patients each, that were positive and negative for all H. pylori tests.\", 'UBiT showed a false-positive rate of 17%, with a specificity of 83%. All the positive controls and 12 of 44 patients (27%) with false-positive UBiT were positive for all two PCR tests; by contrast, none of our negative controls had two positive PCR tests.",
            "output": [
                "Does occult H. pylori infection partially explain 'false-positive ' results of ( 13 ) C-urea breath test?"
            ]
        },
        {
            "id": "task847-4dee7e95cb864b339ed3255230b48b0c",
            "input": "Impaired diabetes wound healing can often lead to serious complications and remains a major health concern due to the lack of effective therapeutic approaches. Compromised angiogenesis, disrupted growth factor and cytokine activity are all attributable to diabetic wound healing impairment. The skin-derived precursors (SKPs) have been shown to differentiate into vascular and nerve cells, both of which are crucial components for wound repair. Given their easy accessibility and multipotency, the SKPs were proposed as an ideal therapeutic candidate for diabetic wound healing. Since the efficacy of cell therapy is limited by poor cell survival, collagen sponge was employed for better SKPs delivery.', 'SKPs were isolated and transplanted directly to the wound areas of diabetic mice in the absence and presence of collagen sponge. The effects of SKPs and/or collagen sponge on diabetic wound healing were examined histologically as well as immunostaining of isolectin and \u03b1-SMA. Mechanisms via which the SKPs facilitate wound healing were then investigated by transplanting SKPs that have been pre-labelled with a fluorescence dye, Dil. Expression patterns of Dil and an SKP marker, nestin, was also examined.",
            "output": [
                "Does co-Transplantation of Skin-Derived Precursors and Collagen Sponge facilitate Diabetic Wound Healing by Promoting Local Vascular Regeneration?"
            ]
        },
        {
            "id": "task847-efe78162d0a7488085871c0af9aa70f3",
            "input": "Despite of many studies conducted on toothbrushes and toothpaste to find out the culprit for abrasion, there is no clear cut evidence to pin point the real cause for abrasion.', 'An in vitro assessment of the role of different types of toothbrushes (soft/ medium/hard) in abrasion process when used in conjunction with and without a dentifrice.', 'Forty five freshly extracted, sound, human incisor teeth were collected for this study. Enamel specimens of approximately 9 mm(2) were prepared by gross trimming of extracted teeth using a lathe machine (Baldor 340 Dental lathe; Ohio, USA). They were mounted on separate acrylic bases. The specimens were divided into three groups, each group containing 15 mounted specimens. Group 1 specimens were brushed with soft toothbrush; Group 2 brushed with medium toothbrush and Group 3 with hard toothbrush. Initially, all the mounted specimens in each group were brushed using dentifrice and then the same procedure was repeated with water as control. Profilometric readings were recorded pre and post to tooth brushing and the differences in readings served as proxy measure to assess surface abrasion. These values were then compared to each other. Kruskal Wallis and Mann-Whitney U test were performed.', 'The results showed that brushing, with water alone, caused less abrasion than when toothpaste was added (p< 0.008). When brushed with water, the harder toothbrush caused more abrasion (higher Ra-value), but when toothpaste was added, the softer toothbrush caused more abrasion (p< 0.001).",
            "output": [
                "Do a Profilometric Study to Assess the Role of Toothbrush and Toothpaste in Abrasion Process?"
            ]
        },
        {
            "id": "task847-daf6c52b3e2a43bba5c1ad42804b11d6",
            "input": "To determine whether anxiety and depression are associated with greater respiratory discomfort in asthma.', 'Adults with asthma (n = 230) underwent methacholine (Mch) challenge. Anxiety and depression, asthma control, and quality of life were evaluated at study entry by using the Hospital Anxiety and Depression Scale, Asthma Control Test, and Asthma Quality of Life Questionnaire, respectively. Qualitative descriptors of breathlessness, dyspnea intensity (modified Borg scale and visual analog scale [VAS]), and other respiratory symptoms were evaluated before and after Mch challenge.', 'Patients were classified as neither anxiety nor depression (NAD), anxiety only, depression only (D), or both anxiety and depression (AD) according to the Hospital Anxiety and Depression Scale score. Asthma Control Test and Asthma Control Test, and Asthma Quality of Life Questionnaire scores were lowest in the AD group (both p < 0.001). VAS scores for dyspnea and wheezing before Mch challenge were highest in the AD group (both p < 0.05). The increase in the modified Borg scale score after Mch challenge was higher in the AD group (mean [standard deviation] 2.5 \u00b1 2.0) than in the NAD (1.5 \u00b1 1.5) and D (0.8 \u00b1 0.9) groups (p = 0.006 and p = 0.003, respectively). Most descriptors of breathlessness were more prevalent in the anxiety only, D, and AD groups than in the NAD group. Multivariable logistic regression models indicated that anxiety increased the risk of dyspnea (odds ratio 1.10, p < 0.001 for the Borg score; odds ratio 3.84, p = 0.032 for the VAS score) but not for other respiratory symptoms.",
            "output": [
                "Are anxiety but not depression symptoms associated with greater perceived dyspnea in asthma during bronchoconstriction?"
            ]
        },
        {
            "id": "task847-0d5b3ac874c64302b25291c110213e37",
            "input": "Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population.', 'We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons.', 'Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852-2.447; p=0.647, OR=0.854, CI=0.436-1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149-0.655).",
            "output": [
                "Is combined glutathione S transferase M1/T1 null genotypes associated with type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-02210d2f58374c70a3572b10ed8bcbc2",
            "input": "To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities.', 'Cross-sectional study.', 'Tertiary academic institution.', 'Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and\\xa02013.', 'International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing.', 'Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR).', \"The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone-binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99).",
            "output": [
                "Is vigorous exercise associated with superior metabolic profiles in polycystic ovary syndrome independent of total exercise expenditure?"
            ]
        },
        {
            "id": "task847-f92af5dd03a34ae2922b4610354dd113",
            "input": "HIV-1-infected and/or immune-activated microglia and macrophages are pivotal in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). Glutaminase, a metabolic enzyme that facilitates glutamate generation, is upregulated and may play a pathogenic role in HAND. Our previous studies have demonstrated that glutaminase is released to the extracellular fluid during HIV-1 infection and neuroinflammation. However, key molecular mechanisms that regulate glutaminase release remain unknown. Recent advances in understanding intercellular trafficking have identified microvesicles (MVs) as a novel means of shedding cellular contents. We posit that during HIV-1 infection and immune activation, microvesicles may mediate glutaminase release, generating excessive and neurotoxic levels of glutamate.', 'MVs isolated through differential centrifugation from cell-free supernatants of monocyte-derived macrophages (MDM) and BV2 microglia cell lines were first confirmed in electron microscopy and immunoblotting. As expected, we found elevated number of MVs, glutaminase immunoreactivities, as well as glutaminase enzyme activity in the supernatants of HIV-1 infected MDM and lipopolysaccharide (LPS)-activated microglia when compared with controls. The elevated glutaminase was blocked by GW4869, a neutral sphingomyelinase inhibitor known to inhibit MVs release, suggesting a critical role of MVs in mediating glutaminase release. More importantly, MVs from HIV-1-infected MDM and LPS-activated microglia induced significant neuronal injury in rat cortical neuron cultures. The MV neurotoxicity was blocked by a glutaminase inhibitor or GW4869, suggesting that the neurotoxic potential of HIV-1-infected MDM and LPS-activated microglia is dependent on the glutaminase-containing MVs.",
            "output": [
                "Do glutaminase-containing microvesicles from HIV-1-infected macrophages and immune-activated microglia induce neurotoxicity?"
            ]
        },
        {
            "id": "task847-03c615b9b68c42c2a24dc358d2710059",
            "input": "Patients with diabetes are at greater risk of cardiovascular events. Insulin resistance (IR) and hyperinsulinaemia are both related to an increased cardiovascular risk, but whether IR predicts coronary heart disease (CHD) independently of other risk factors in patients with type 2 diabetes (T2D) is a topic of considerable controversy. The aim of the present study was to evaluate the prospective relationship of fasting insulin, HOMA-IR, fasting plasma glucose (FPG) and 2-h post-load glucose (2hPG) load with CHD incidence among such patients.', 'A total of 2607 patients with T2D were enrolled in a community-dwelling cohort and followed for an average of 7.2 years. Conventional CHD risk factors, FPG, 2hPG, fasting insulin levels and HOMA-IR index were measured at baseline. Cox regression hazard ratios (HRs) were used to assess CHD risk.', \"A total of 299 'hard' CHD events were registered (in 114 women and 185 men). Increasing levels of fasting insulinaemia were positively associated with CHD incidence. This correlation persisted after controlling for gender, body mass index, blood pressure, lipid profile, medication use and HbA1c [HR for each increase in quartile (fully adjusted model): 1.18 (95% CI: 1.06-1.32); P<0.01]. 2hPG showed a non-linear association with incident CHD [HR of highest vs lowest quartile: 1.64 (95% CI: 1.03-2.61)]. Fasting glycaemia was not associated with CHD risk, whereas HOMA-IR had a direct and independent correlation with CHD risk [HR for each one-quartile increase: 1.19 (95% CI: 1.07-1.34); P<0.01].",
            "output": [
                "Do fasting hyperinsulinaemia and 2-h glycaemia predict coronary heart disease in patients with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-9765de7618eb46d1bd9bae73324063f4",
            "input": "Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement.', 'Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance-based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis.', 'Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1.",
            "output": [
                "Is mechanical stress associated with right ventricular response to pulmonary valve replacement in patients with repaired tetralogy of Fallot?"
            ]
        },
        {
            "id": "task847-a82f7eed797f490c870ceb9521947555",
            "input": "To evaluate the efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) in the laser-induced mouse model of choroidal neovascularization (CNV).', \"We evaluated the NRTIs lamivudine (3TC), zidovudine (AZT), and abacavir (ABC) and the P2X7 antagonist A438079. Choroidal neovascularization was induced by laser injury in C57BL/6J wild-type, Nlrp3-/-, and P2rx7-/- mice, and CNV volume was measured after 7 days by confocal microscopy. Drugs were administered by intravitreous injection immediately after the laser injury. Vascular endothelial growth factor-A in RPE-choroid lysates was measured 3 days after laser injury by ELISA. HEK293 cells expressing human and mouse P2X7 were exposed to the selective P2X7 receptor agonist 2', 3'-(benzoyl-4-benzoyl)-ATP (Bz-ATP) with or without 3TC, and VEGF-A levels in media were measured by ELISA.\", 'Intravitreous injection of 3TC, AZT, and ABC significantly suppressed laser-induced CNV in C57BL/6J wild-type and Nlrp3-/- mice (P < 0.05) but not in P2rx7-/- mice. Intravitreous injection of A438079 also suppressed the laser-induced CNV (P < 0.05). The NRTIs 3TC, AZT, and ABC blocked VEGF-A levels in the RPE/choroid after laser injury in wild-type (P < 0.05) but not P2rx7-/- mice. Moreover, there was no additive effect of 3TC on CNV inhibition when coadministered with a neutralizing VEGF-A antibody. Stimulation of human and mouse P2X7-expressing HEK293 cells with Bz-ATP increased VEGF secretion (P < 0.001), which was abrogated by 3TC (P < 0.001). Stimulation of primary human RPE cells with Bz-ATP increased VEGFA and IL6 mRNA levels, which were abrogated by 3TC.",
            "output": [
                "Do nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice?"
            ]
        },
        {
            "id": "task847-e11f65a5acad4116befb997564870baa",
            "input": "To assess the association of obesity and postoperative complications after operative management of tibial shaft fractures.', 'Patients who underwent operative management of a tibial shaft fracture were identified in a national database by Current Procedural Terminology (CPT) codes for: (1) open reduction and internal fixation (ORIF) and (2) intramedullary nailing (IMN) procedures in the setting of International Classification of Diseases, Ninth Revision (ICD-9) codes for tibial shaft fracture. These groups were then divided into non-obese, obese, and morbidly obese cohorts using ICD-9 codes. Each cohort was then assessed for grouped complications within 90 days, removal of implants within 6 months, and nonunion within 9 months postoperatively. Odds ratios and 95% confidence intervals were calculated.', 'From 2005 to 2012, 14,638 patients who underwent operative management of tibial shaft fractures were identified, including 4425 (30.2%) ORIF and 10,213 (69.8%) IMN. Overall, 1091 patients (7.4%) were coded as obese and 820 (5.6%) morbidly obese. In each operative group, obesity and morbid obesity was associated with a substantial increase in the rate of major and minor medical complications, venous thromboembolism, infection, procedures for implant removal, and nonunion.",
            "output": [
                "Is obesity associated with increased postoperative complications after operative management of tibial shaft fractures?"
            ]
        },
        {
            "id": "task847-79627ed181514be1a4a25f49cb8570f1",
            "input": "Normal pressure hydrocephalus is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality, and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, multiple overlapping symptoms often make it difficult to differentiate normal pressure hydrocephalus from other types of dementia, and improved diagnostic techniques would help patient management. MR elastography is a novel diagnostic tool that could potentially identify patients with normal pressure hydrocephalus. The purpose of this study was to assess brain stiffness changes in patients with normal pressure hydrocephalus compared with age- and sex-matched cognitively healthy individuals.', 'MR elastography was performed on 10 patients with normal pressure hydrocephalus and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MR imaging scanner. Shear waves with 60-Hz vibration frequency were transmitted into the brain by a pillowlike passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis.', 'A significant increase in stiffness was observed in the cerebrum (P = .001), occipital lobe (P < .001), parietal lobe (P = .001), and the temporal lobe (P = .02) in the normal pressure hydrocephalus group compared with healthy controls. However, no significant difference was noted in other regions of the brain, including the frontal lobe (P = .07), deep gray and white matter (P = .43), or cerebellum (P = .20).",
            "output": [
                "Does mR Elastography demonstrate Increased Brain Stiffness in Normal Pressure Hydrocephalus?"
            ]
        },
        {
            "id": "task847-23ec515f08cf4f8598b72da718ef4bdf",
            "input": "Health care-associated infections result in significant patient morbidity and mortality. Although cleaning can remove pathogens present on hospital surfaces, those surfaces may be inadequately cleaned or recontaminated within minutes. Because of copper's inherent and continuous antimicrobial properties, copper surfaces offer a solution to complement cleaning. The objective of this study was to quantitatively assess the bacterial microbial burden coincident with an assessment of the ability of antimicrobial copper to limit the microbial burden associated with 3 surfaces in a pediatric intensive care unit.\", 'A pragmatic trial was conducted enrolling 1,012 patients from 2 high acuity care units within a\\xa0249-bed tertiary care pediatric hospital over 12 months. The microbial burden was determined from 3\\xa0frequently encountered surfaces, regardless of room occupancy, twice monthly, from 16 rooms, 8\\xa0outfitted normally and 8 outfitted with antimicrobial copper.', 'Copper surfaces were found to be equivalently antimicrobial in pediatric settings to activities reported for adult medical intensive care units. The log10 reduction to the microbial burden from antimicrobial copper surfaced bed rails was 1.996 (99%). Surprisingly, introduction of copper objects to 8\\xa0study rooms was found to suppress the microbial burden recovered from objects assessed in control rooms by log10 of 1.863 (73%).",
            "output": [
                "Are copper surfaces associated with significantly lower concentrations of bacteria on selected surfaces within a pediatric intensive care unit?"
            ]
        },
        {
            "id": "task847-4473b62976694727a76256cf450217aa",
            "input": "Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement.', 'We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14\\u2005weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12\\u2005weeks. Total serum type I IFN activity, IFN-\u03b1 and IFN-\u03b2 activity were measured using a functional reporter cell assay.', 'In the test set, an increased ratio of IFN-\u03b2 to IFN-\u03b1 (IFN-\u03b2/\u03b1 activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-\u03b2/\u03b1 activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-\u03b2/\u03b1 activity ratio (p=0.005).",
            "output": [
                "Does increased pretreatment serum IFN-\u03b2/\u03b1 ratio predict non-response to tumour necrosis factor \u03b1 inhibition in rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-bbf8445d46b5436784241a6ffadf2ac7",
            "input": "Studies have shown that rectal distension has a significant impact on treatment failure in patients receiving radical radiotherapy for prostate cancer. A distended rectum contributes to excessive organ movement during treatment, resulting in significant underdosing of the target volume and higher treatment failure rates. The increasing use of highly conformal, precise radiotherapy techniques places greater importance on reducing this risk. We tested whether imaging during radiotherapy helps minimise the negative impact that rectal distension has on long-term tumour control.', 'The rectal diameter (anterior/posterior and lateral) was prospectively measured at radiotherapy planning in 172 consecutive patients undergoing radical radiotherapy with three-dimensional conformal radiotherapy. Daily, and then weekly, imaging during radiotherapy ensured that prostate movement remained within predefined tolerances. Patients were followed up for a median of 72 months with regular prostate-specific antigen (PSA) measurements to ascertain biochemical PSA relapse and survival information.",
            "output": [
                "Is degree of Rectal Distension Seen on Prostate Radiotherapy Planning CT Scan a Negative Prognostic Factor in the Modern Era of Image-Guided Radiotherapy?"
            ]
        },
        {
            "id": "task847-8fd96738d9174aca9da0f1e8ea932315",
            "input": "MicroRNAs play important roles in the adaptive responses of plants to nutrient deficiencies. Most research, however, has focused on nitrogen (N), phosphorus (P), sulfur (S), copper (Cu) and iron (Fe) deficiencies, limited data are available on the differential expression of miRNAs and their target genes in response to deficiencies of other nutrient elements. In this study, we identified the known and novel miRNAs as well as the boron (B)-deficiency-responsive miRNAs from citrus leaves in order to obtain the potential miRNAs related to the tolerance of citrus to B-deficiency.', \"Seedlings of 'Xuegan' [Citrus sinensis (L.) Osbeck] were supplied every other day with B-deficient (0 \u03bcM H3BO3) or -sufficient (10 \u03bcM H3BO3) nutrient solution for 15 weeks. Thereafter, we sequenced two small RNA libraries from B-deficient and -sufficient (control) citrus leaves, respectively, using Illumina sequencing.\", 'Ninety one (83 known and 8 novel) up- and 81 (75 known and 6 novel) down-regulated miRNAs were isolated from B-deficient leaves. The great alteration of miRNA expression might contribute to the tolerance of citrus to B-deficiency. The adaptive responses of miRNAs to B-deficiency might related to several aspects: (a) attenuation of plant growth and development by repressing auxin signaling due to decreased TIR1 level and ARF-mediated gene expression by altering the expression of miR393, miR160 and miR3946; (b) maintaining leaf phenotype and enhancing the stress tolerance by up-regulating NACs targeted by miR159, miR782, miR3946 and miR7539; (c) activation of the stress responses and antioxidant system through down-regulating the expression of miR164, miR6260, miR5929, miR6214, miR3946 and miR3446; (d) decreasing the expression of major facilitator superfamily protein genes targeted by miR5037, thus lowering B export from plants. Also, B-deficiency-induced down-regulation of miR408 might play a role in plant tolerance to B-deficiency by regulating Cu homeostasis and enhancing superoxide dismutase activity.",
            "output": [
                "Does boron-deficiency-responsive microRNAs and their targets in Citrus sinensis leave?"
            ]
        },
        {
            "id": "task847-7f300c910edb4e7ea2cc8d801d86d9c1",
            "input": "The cyclin-dependent kinase inhibitor 3 (CDKN3) has been perceived as a tumour suppressor. Paradoxically, CDKN3 is often overexpressed in human cancer. It was unclear if CDKN3 overexpression is linked to alternative splicing variants or mutations that produce dominant-negative CDKN3.', \"We analysed CDKN3 expression and its association with patient survival in three cohorts of lung adenocarcinoma. We also examined CDKN3 mutations in the Cancer Genome Atlas (TCGA) and the Moffitt Cancer Center's Total Cancer Care (TCC) projects. CDKN3 transcripts were further analysed in a panel of cell lines and lung adenocarcinoma tissues. CDKN3 mRNA and protein levels in different cell cycle phases were examined.\", 'CDKN3 is overexpressed in non small cell lung cancer. High CDKN3 expression is associated with poor overall survival in lung adenocarcinoma. Two CDKN3 transcripts were detected in all samples. These CDKN3 transcripts represent the full length CDKN3 mRNA and a normal transcript lacking exon 2, which encodes an out of frame 23-amino acid peptide with little homology to CDKN3. CDKN3 mutations were found to be very rare. CDKN3 mRNA and protein were elevated during the mitosis phase of cell cycle.",
            "output": [
                "Is overexpression of major CDKN3 transcripts associated with poor survival in lung adenocarcinoma?"
            ]
        },
        {
            "id": "task847-87d8c036a99845afa7307f3afc14fca3",
            "input": "The aim of this study was to investigate whether fibroblast growth factor receptor 4 (FGFR4) could serve as a potential therapeutic target, prognostic biomarker or biomarker predicting radiotherapy sensitivity in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC).', 'FGFR4 immunohistochemistry and FGFR4/CEN5q FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. FGFR4 genotypes were determined by PCR and DNA sequencing in 76 random OPSCC samples. The response to radiotherapy was evaluated 3 months after the last radiotherapy treatment session by a head and neck radiation oncologist and/or surgeon during clinic visits. The results were correlated to overall survival and response to radiotherapy.', 'The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The FGFR4 gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the FGFR4 Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, FGFR4 gene copy numbers and FGFR4 genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC.",
            "output": [
                "Does fGFR4 be a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma?"
            ]
        },
        {
            "id": "task847-bfde0363536c481d8eef24b4aafecaf0",
            "input": "The aim of the present study was to evaluate baseline regional cerebral oxygen saturation (rSO2) values and identify factors influencing preoperative rSO2 in elective minor surgery.', 'Observational analysis post-hoc.', 'Observational post-hoc analysis of data for the patient sample (n=50) of a previously conducted clinical trial in patients undergoing tumourectomy for breast cancer or inguinal hernia repair. Exclusion criteria included pre-existing cerebrovascular diseases, anaemia, baseline pulse oximetry <97% and low quality rSO2 sensor signals. Demographic data, comorbidities, and ASA physical status as well as height and weight were collected prospectively from all patients. Baseline rSO2 values were recorded while the patient breathed room air, using the INVOS 5100C monitor\u2122 (Covidien, Dublin, Ireland).', 'Thirty-seven women (72%) and 13 men (28%) 48 \u00b1 13 years of age were enrolled in this study. Baseline rSO2 was 62.01 \u00b1 10.38%. Baseline rSO2 was significantly different between men (67.6 \u00b1 11.2%) and women (60 \u00b1 9.4%), (P=0.023). There were also differences between baseline rSO2 and ASA physical status (ASA I: 67.6 \u00b1 10.7%, ASA II: 61.6 \u00b1 8.4%, ASA III: 55.8 \u00b1 13.9%, P=0.045). Baseline rSO2 had a positive correlation with body weight (r=0.347, P=0.014) and height (r=0.345, P=0.014). We also found significant differences in baseline rSO2 among patients with and without chronic renal failure (P=0.005). No differences were found in any other studied variables.",
            "output": [
                "Do baseline cerebral oximetry values depend on non-modifiable patient characteristics?"
            ]
        },
        {
            "id": "task847-3132f2e48fe243098d838bae6c81a770",
            "input": "Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC.', 'The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues.', 'We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009).",
            "output": [
                "Is global DNA hypomethylation associated with the development and poor prognosis of tongue squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-a7509d908c0946a88f060992dbaa8591",
            "input": "Recent reviews of reproductive isolation (RI) in plants propose that boundaries between closely related species are maintained predominantly through prezygotic mechanisms. However, few experimental studies have explored how boundaries are maintained in long-lived species. Hawaiian Cyrtandra presents an intriguing challenge to our understanding of RI, as it comprises 60 shrub or small tree species that are almost exclusively restricted to wet forests, where sympatry of multiple species is common.', \"We assessed the relative strengths of pre- and postzygotic barriers among four species of Cyrtandra occurring at the extremes of the main Hawaiian Island's natural island-age gradient, Kaua'i (4.7 Myr) and Hawai'i Island (0.6 Myr), to contrast the strengths and stages of reproductive isolation among species at different stages of divergence.\", 'A combination of F1 seed germination, F1 seedling survival, and F1 seedling growth isolated (61-91%) three of the species from sympatric relatives. In contrast, the fourth species was isolated (59%) from its sympatric relative through phenological differences alone. Significant postzygotic barriers in between-island crosses were also observed in one species.",
            "output": [
                "Do postzygotic barriers isolate sympatric species of Cyrtandra ( Gesneriaceae ) in Hawaiian montane forest understories?"
            ]
        },
        {
            "id": "task847-03f2ddddcd6d41b2b3d1f80cb739ea6c",
            "input": "Although much attention has focused on the diversity of plant mating systems, only a few studies have considered the joint effects of mating system and sexual conflict in plant evolution. In mixed-mating Collinsia heterophylla, a sexual conflict over timing of stigma receptivity is proposed: pollen with a capacity to induce early onset of stigma receptivity secures paternity for early-arriving pollen (at the expense of reduced maternal seed set), whereas late onset of stigma receptivity mitigates the negative effects of early-arriving pollen. Here we investigated whether selection on pollen and pistil traits involved in sexual conflict is affected by the presence of both outcross- and self-pollen (mixed mating) during pollen competition.', 'We conducted two-donor crosses at different floral developmental stages to explore male fitness (siring ability) and female fitness (seed set) in relation to male and female identity, pollen and pistil traits, and type of competitor pollen (outcross vs. self).', 'Late-fertilizing pollen rather than rapidly growing pollen tubes was most successful in terms of siring success, especially in competition with self-pollen after pollination at early floral stages. Late stigma receptivity increased seed set after early-stage pollinations, in agreement with selection against antagonistic pollen.",
            "output": [
                "Is selection on pollen and pistil traits during pollen competition affected by both sexual conflict and mixed mating in a self-compatible herb?"
            ]
        },
        {
            "id": "task847-334fc2cb133544daaa51b15e86dcaf82",
            "input": "The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure-activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed.', 'We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP).",
            "output": [
                "Does identification of structural alert for liver and kidney toxicity using repeated dose toxicity data?"
            ]
        },
        {
            "id": "task847-c7705ba686544ca8a67059be3da3f5f9",
            "input": "Cyclophosphamide is commonly used as an important component in conditioning prior to hematopoietic stem cell transplantation, a curative treatment for several hematological diseases. Cyclophosphamide is a prodrug activated mainly by cytochrome P450 2B6 (CYP2B6) in the liver. A high degree of inter- and intra-individual variation in cyclophosphamide kinetics has been reported in several studies.', 'Hydroxylation of cyclophosphamide was investigated in vitro using three microsomal batches of CYP2B6*1 with different ratios of POR/CYP expression levels. Twenty patients undergoing hematopoietic stem cell transplantation were also included in the study. All patients received an i.v. infusion of cyclophosphamide (60 mg/kg/day, for two days) as a part of their conditioning. Blood samples were collected from each patient before cyclophosphamide infusion, 6 h after the first dose and before and 6 h after the second dose. POR gene expression was measured by mRNA analysis and the pharmacokinetics of cyclophosphamide and its active metabolite were determined.', 'A strong correlation between the in vitro intrinsic clearance of cyclophosphamide and the POR/CYP ratio was found. The apparent Km for CYP2B6.1 was almost constant (3-4 mM), while the CLint values were proportional to the POR/CYP ratio (3-34 \u03bcL/min/nmol CYP). In patients, the average expression of the POR gene in blood was significantly (P <0.001) up-regulated after cyclophosphamide infusion, with high inter-individual variations and significant correlation with the concentration ratio of the active metabolite 4-hydroxy-cyclophosphamide/cyclophosphamide. Nine patients were carriers for POR*28; four patients had relatively high POR expression.",
            "output": [
                "Does cytochrome P450 Oxidoreductase influence CYP2B6 Activity in Cyclophosphamide Bioactivation?"
            ]
        },
        {
            "id": "task847-f9ed195ad5bc42b2995dd279b66051bb",
            "input": "Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate.', 'An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor.', 'Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1\u03b1, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well.",
            "output": [
                "Does targeting glycolysis by 3-bromopyruvate improve tamoxifen cytotoxicity of breast cancer cell lines?"
            ]
        },
        {
            "id": "task847-9ba8319b5bd240249020156d85adbf50",
            "input": "Beta2-glycoprotein I (\u03b22GPI) is a highly abundant glycoprotein in plasma. Our previous study demonstrated strong \u03b22GPI expression in hepatitis B-related hepatocellular carcinoma (HCC) tissue and the combination of \u03b22GPI and hepatitis B surface antigen (HBsAg) was shown to significantly activate the nuclear factor kappa B (NF-\u03baB). To investigate whether lipopolysaccharide (LPS) enhances \u03b22GPI activation of NF-\u03b2B and the expression of downstream factors (e.g., tumor necrosis factor alpha, TNF-\u03b1; interleukin-1 beta, IL-1\u03b2; alpha-fetoprotein, AFP) in the human hepatoma cell line, SMMC-7721.', 'Experimental samples were divided into 4 groups as follows: Group A--blank cell group (SMMC-7721); group B--low, medium, and high LPS concentration groups (1 ng/mL; 10 ng/mL; and 100 ng/mL, respectively); group C--\u03b22GPI transfected group; and group D--\u03b22GPI + low, medium, or high concentrations from the LPS affected group. Activation of NF-\u03baB was evaluated using laser scanning confocal microscopy. Expression of downstream factors was measured by ELISA.', 'Degrees of NF-\u03baB activation in groups B, C, and D were varied. NF-\u03baB activation in group D was the most significant, and the expressions of downstream factors, TNF-\u03b1 and IL-1\u03b2, were the highest level of activation among the groups (p < 0.05), showing an LPS dose-dependency.",
            "output": [
                "Does lipopolysaccharide enhance Beta2-Glycoprotein I Activation of Nuclear Factor \u03baB in Liver Cancer Cells?"
            ]
        },
        {
            "id": "task847-3f75bd6a7035462699f40ccfadd07cbe",
            "input": "It has been demonstrated that photodynamic therapy (PDT) is a promising treatment approach for hyperplastic dermatosis and results in a beneficial outcome. In the present study, PDT involving hematoporphyrin monomethyl ether (HMME) was applied to keloid fibroblasts (KFB), and the effects and the mechanism of action were explored.', 'Keloid fibroblastic cells were divided into four groups (PDT group, light alone group, HMME alone group, normal cultured group). Cell proliferation and apoptosis were observed. Radical oxygen species (ROS) were detected by means of dihydroethidium (DHE) and dihydrorhodamine (DHR123). ROS in the PDT group were also assessed after addition of tiron.', 'Cell proliferation was inhibited in the PDT group (p < 0.05), while the rate of apoptosis was also clearly increased (p < 0.05). The levels of ROS were significantly higher in the PDT group than was observed in the other three groups (p < 0.05). With the addition of tiron the damaging effects were reduced.",
            "output": [
                "Is photodynamic Therapy-Induced Apoptosis of Keloid Fibroblasts Mediated by Radical Oxygen Species In Vitro?"
            ]
        },
        {
            "id": "task847-2deea3d4091b4760a8b0affb71ff44f8",
            "input": "i ne prognostic relevance of hematological parameters in cardiovascular diseases has been well demonstrated. The purpose of the present study is to investigate the association between the hematological parameters, particularly neutrophil to lymphocyte ratio (NLR), and outcomes of aortic dissection (AD).', 'Two hundred patients diagnosed with AD were retrospectively recruited and compared with 76 subjects with ascending aortic dilatation (AAD) and 92 subjects with normal aortic diameters. The independent relation between hematological parameters and in-hospital mortality was analyzed by regression analysis.', 'The NLR was significantly higher in the AD group compared to the AAD and control groups (median 8.83 [8.13] vs. median 1.95 [1.10] vs. median 1.71 [0.77], respectively; p = 0.01). The NLR was higher in the deceased (n = 57) compared to the surviving patients (n = 143) (median 10.37 [10.86] vs. median 7.84 [8.17]; p = 0.01). Receiver operating curve (ROC) analysis revealed that a NLR measurement higher than > 8.78 predicted in-hospital mortality for patients with acute aortic dissection with a sensitivity of 67.4% and a specificity of 57.2% (AUC: 0.672; p = 0.01). In multivariate logistic regression analysis, increased aortic diameter, acute dissection, and increased levels of NLR remained as the independent markers of in-hospital mortality within the study population.",
            "output": [
                "Is increased Neutrophil to Lymphocyte Ratio Associated with In-Hospital Mortality in Patients with Aortic Dissection?"
            ]
        },
        {
            "id": "task847-a895cf3f16dd4852acadc6074488754a",
            "input": "To determine GJB2 allelic mutant and estimate probability of hereditary hearing loss in newborn with GJB2 heterozygous mutation in Beijing.', 'We performed genetic testing for sequencing of GJB2 gene for searching GJB2 allelic mutant in 915 newborn who received newborn deafness gene screening (GJB2 c. 235delC, GJB2 c. 299_300delAT, GJB2 c. 176191del16, GJB2 c. 35delG) in Beijing Tongren hospital, and the mutation were classified to pathogenic mutation,undefined variant and polymorphism.', 'Four hundred (43.72%, 400/915) newborn were detected to carry at least one mutation allele in GJB2. 3 (0.33%, 3/915) newborn had pathogenic mutations (c. 94C>T, c. 380G>T, c. 344T>G); 62 (6.76%, 62/915) newborn carried 14 undefined variant, 36 newborn had c. 109G>A (58.06%, 36/62),13 newborn had c. 368C>A (20.97%,13/62), six (c. 268C>G, c. 282C>T, c. 294G>C, 456C>T, c. 501G>A, c. 587T>C) are novel; 335 (36.61%, 335/915) newborn were polymorphism.",
            "output": [
                "Do [ The sequencing analyze of 915 newborn with GJB2 heterozygous mutation in Beijing ]?"
            ]
        },
        {
            "id": "task847-c51bb3c584ee46018bf73ebf6f573e85",
            "input": "To determine whether obese patients undergoing laparoscopic surgery within an enhanced recovery program had worse short-term outcomes.', 'A prospective study of consecutive patients undergoing laparoscopic colorectal resection was carried out between 2008 and 2011 in a single institution. Patients were divided in groups based on body mass index (BMI). Short-term outcomes including operative data, length of stay, complications and readmission rates were recorded and compared between the groups. Continuous data were analysed using t-test or one-way Analysis of Variance. \u03c7(2) test was used to compare categorical data.', 'Two hundred and fifty four patients were included over the study period. The majority of individuals (41.7%) recruited were of a healthy weight (BMI < 25), whilst 50 patients were classified as obese (19.6%). Patients were matched in terms of the presence of co-morbidities and previous abdominal surgery. Obese patients were found to have a statistically significant difference in The American Society of Anesthesiologists grade. Length of surgery and intra-operative blood loss were no different according to BMI.",
            "output": [
                "Do obese patients have similar short-term outcomes to non-obese in laparoscopic colorectal surgery?"
            ]
        },
        {
            "id": "task847-c49d934bc968461fb1eb458f6c3e4a4e",
            "input": "A large body of research suggests that light or moderate alcohol consumption is associated with reduced all-cause mortality. However, concerns remain that the observed relationship is due to selection bias, misclassification of ex-drinkers, or residual confounding.', 'The association between alcohol consumption and all-cause mortality was analyzed using Cox regression. The analysis was performed using data from the Health and Retirement Study, a longitudinal cohort of 24,029 individuals from a nationally representative sample of US adults aged more than 50 years. Drinking level was based on alcohol consumption measured at 3 points over the 4 years before the start of follow-up. Occasional drinkers-those who reported drinking on at least 1 occasion, but always less than once per week-served as the reference category. There was extensive adjustment for sociodemographic variables, health status, and functional status.', 'During 206,966 person-years of follow up, 7902 individuals died. No level of regular alcohol consumption was associated with reduced all-cause mortality. The hazard ratio and 95% confidence interval in fully adjusted analyses was 1.02 (0.94-1.11) for <7 drinks/week, 1.14 (1.02-1.28) for 7 to <14 drinks/week, 1.13 (0.96-1.35) for 14 to <21 drinks/week, and 1.45 (1.16-1.81) for \u2265 21 drinks/week.",
            "output": [
                "Is moderate Alcohol Consumption Associated with Reduced All-cause Mortality?"
            ]
        },
        {
            "id": "task847-16929c721963436a8f26ae107b6a69c7",
            "input": "Colorectal cancer is common in developed countries. Polyunsaturated fatty acids (PUFAs) have been reported to possess tumoricidal action, but the exact mechanism of their action is not clear.', 'In the present study, we studied the effect of various n-6 and n-3 fatty acids on the survival of the colon cancer cells LoVo and RKO and evaluated the possible involvement of a mitochondrial pathway in their ability to induce apoptosis.', 'It was observed that n-3 \u03b1-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (ALA, EPA and DHA respectively) and n-6 linoleic acid, gamma-linolenic acid and arachidonic acid (LA, GLA and AA respectively) induced apoptosis of the colon cancer cells LoVo and RKO at concentrations above 120 \u03bcM (p < 0.01 compared to control). The semi-differentiated colon cancer cell line RKO was more sensitive to the cytotoxic action of PUFAs compared to the undifferentiated colon cancer cell line LoVo. PUFA-treated cells showed an increased number of lipid droplets in their cytoplasm. PUFA-induced apoptosis of LoVo and RKO cells is mediated through a mitochondria-mediated pathway as evidenced by loss of mitochondrial membrane potential, generation of ROS, accumulation of intracellular Ca(2+), activation of caspase-9 and caspase-3, decreased ATP level and increase in the Bax/Bcl2 expression ratio.",
            "output": [
                "Do polyunsaturated fatty acids trigger apoptosis of colon cancer cells through a mitochondrial pathway?"
            ]
        },
        {
            "id": "task847-65bacc3eba28424793aa70ae3675c386",
            "input": "Oxidative stress has been considered to play a primary role in the pathogenesis of stress-induced gastric damage. The aim of this study was to investigate the effects of melatonin, ascorbic acid and \u03b2-carotene on stress-induced gastric mucosal damage.', 'Fifty-six male Wistar albino rats were divided into control, stress, stress + standard diet, stress + saline, stress + melatonin, stress + ascorbic acid and stress + \u03b2-carotene groups. The rats from stress groups were exposed to starvation, immobilization and cold by immobilizing for 8 h at +4\u00b0C following 72-hour food restriction. Following stress application, melatonin, ascorbic acid and \u03b2-carotene were administered for 7 days. Specimens of gastric tissue were prepared for microscopic and biochemical examinations.', 'Mean histopathological damage scores and mean tissue malondialdehyde levels were significantly decreased but mean tissue glutathione levels and glutathione peroxidase and superoxide dismutase activities were increased in treatment groups vs. stress groups in general. Mean histopathological damage scores of the stress + Mel group was lower than those of stress + D, stress + S, stress + \u03b2-car (p < 0.05) and stress + Asc groups (p < 0.005). Additionally, mean tissue catalase activity of the stress + Mel group was higher than that of stress + S (p < 0.005), stress + D (p < 0.05) and stress + \u03b2-car groups (p < 0.05).",
            "output": [
                "Is melatonin more effective than ascorbic acid and \u03b2-carotene in improvement of gastric mucosal damage induced by intensive stress?"
            ]
        },
        {
            "id": "task847-d3d9b2177df34b6080ddb541ce55ed34",
            "input": "Events in the lungs might contribute to generation of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). We investigated if signs of immune activation are present in bronchial biopsies and bronchoalveolar lavage (BAL) of patients with early-untreated RA without clinical signs of lung involvement.', 'Twenty-four patients with RA with symptom duration <1\\u2005year and na\u00efve to disease-modifying antirheumatic drugs were subjected to bronchoscopy where BAL and mucosal bronchial biopsies were retrieved. For comparison, 15 bronchial biopsies and 79 BAL samples from healthy volunteers were available. Histological examination was performed to evaluate lymphocyte infiltration, presence of immune cells (T and B cells, plasma cells, dendritic cells and macrophages) and immune activation markers. Cell composition of BAL samples was analysed by differential counting and T cell subsets by flow cytometry.', 'Lymphocyte infiltration was more frequently found in ACPA-positive patients (50%) as compared with ACPA-negative patients (17%) and controls (13%). Germinal centres, B cells and plasma cells were only found in ACPA-positive patients. The frequency of T cells in bronchial biopsies of patients with ACPA-positive RA was positively associated with expression of immune activation markers. BAL samples of patients with ACPA-positive, but not ACPA-negative, RA had significantly higher relative numbers of lymphocytes and expressed higher levels of activation markers compared with controls.",
            "output": [
                "Are signs of immune activation and local inflammation present in the bronchial tissue of patients with untreated early rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-d92c8a329269477ebdea53f54135cd6e",
            "input": "Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients.', 'A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses.', 'In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=-5.60 95% CI=-7.65 to -3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant.",
            "output": [
                "Is cannabis use disorder associated with greater illness severity in tobacco smoking patients with bipolar disorder?"
            ]
        },
        {
            "id": "task847-5f7ae65297804706937b14ad21bc62f3",
            "input": "We asked whether anxiety is associated with prospective risk of dementia, and the extent to which genetic influences mediate this association.', 'Nondemented twins (n = 1082) from the Swedish Adoption Twin Study of Aging completed an assessment of anxiety symptoms in 1984 and were followed for 28 years.', 'Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up (hazard ratio [HR] = 1.04; 95% confidence interval [CI] = 1.01-1.06). There was 48% increased risk of becoming demented for those who had experienced high anxiety at any time compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic (HR = 1.11; 95% CI = 1.02-1.20) compared with monozygotic twins (HR = 1.06; 95% CI = 0.95-1.20), indicating genetic mediation.",
            "output": [
                "Is anxiety associated with increased risk of dementia in older Swedish twins?"
            ]
        },
        {
            "id": "task847-2f59d15c1c904d3a8b0dc4f4e2c11c94",
            "input": "Oxidative stress has been reported to be involved in numerous human diseases, including musculoskeletal disorders such as osteoarthritis. However, the interaction between intervertebral disc (IVD) degeneration and oxidative stress is not well understood. The purpose of the present study was to elucidate the contribution of oxidative stress to IVD degeneration and the efficacy of antioxidant treatment for degenerative discs.', 'The expression level of an oxidative stress marker, nitrotyrosine, was assessed by immunohistochemistry and Western blotting. For evaluating intracellular reactive oxygen species (ROS) levels and oxidative stress in rat annulus fibrosus (AF) cells, flow cytometry and luciferase assay with an OKD48 construct were performed. The grade of IVD degeneration was assessed by magnetic resonance imaging and histological analysis.', 'A high frequency of nitrotyrosine-positive cells was observed in rat and human degenerative discs. mRNA expression of catabolic factors such as tumor necrosis factor-alpha (TNF-alpha), matrix metalloprotease-3 (MMP-3), and cyclooxygenase-2 (COX-2) was significantly induced by treatment with H2O2 or buthionine sulfoximine, whereas that of aggrecan, an important chondrogenic proteoglycan, was reduced in a dose-dependent manner. Treatment with mitogen-activated protein kinase (MAPK) inhibitors blocked the inductive effect of excessive ROS on COX-2 mRNA expression. Western blotting confirmed the phosphorylation of MAPKs in H2O2 and BSO-treated AF cells. Conversely, we showed that TNF-\u03b1 induced oxidative stress with increased intracellular ROS levels in AF cells. Treatment with the antioxidant N-acetyl cysteine (NAC) abrogated the catabolic effect of excessive ROS and TNF-alpha in vitro. Finally, we showed that oral administration of NAC prevented IVD degeneration in rat degenerative model.",
            "output": [
                "Are excessive reactive oxygen species therapeutic targets for intervertebral disc degeneration?"
            ]
        },
        {
            "id": "task847-c8a8aa1beb9f4aa78c91f5c76e98c328",
            "input": "Acute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. Gain of supernumerary copies of the 8q24 chromosomal region, which harbors MYC and PVT1, has been shown to be the most common secondary alteration in human APL. Increased MYC can accelerate the development of myeloid leukemia in APL. However, the role that the expression of the long non-coding RNA (lncRNA) PVT1 plays in the pathogenesis of APL remains largely unknown.', 'In this study, we first analyzed the lncRNA PVT1 expression level in peripheral blood cells from 28 patients with de novo APL, and significantly upregulated PVT1 was found in APL patients compared with healthy donors. We then observed significantly lower MYC and PVT1 expression during all-trans retinoic acid (ATRA)-induced differentiation and cell cycle arrest in the APL cell line. MYC knockdown in NB4 cells led to PVT1 downregulation. Moreover, PVT1 knockdown by RNA interference led to suppression of the MYC protein level, and cell proliferation was inhibited.",
            "output": [
                "Is overexpression of the long non-coding RNA PVT1 correlated with leukemic cell proliferation in acute promyelocytic leukemia?"
            ]
        },
        {
            "id": "task847-d5869e6e98cd4dd980fcc5e408ac9da0",
            "input": "Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis.', 'To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis).', 'The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05).",
            "output": [
                "Does angiogenesis and proliferation of bile duct enhance ischemic tolerance in rats with cirrhosis?"
            ]
        },
        {
            "id": "task847-9351aa04a1ab454b933f4e5e4b5a18fe",
            "input": "Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect.', 'Seven-day-old Sprague-Dawley rats were subjected to brain HI and randomly allocated to 10 groups (n=24 each group) and treated as follows: (1) Sham, without hypoxia-ischemia; (2) HI/Control, received cerebral hypoxia-ischemia; (3) HI+Atractyloside (Atr), (4) HI+Cyclosporin A (CsA), (5) HI+sevoflurane (Sev), (6) HI+Sev+ LY294002 (LY), (7) HI+Sev+ L-NAME (L-N), (8) HI+Sev+ SB216763 (SB), (9) HI+Sev+Atr, and (10) HI+Sev+CsA. Twelve rats in each group underwent behavioral testing and their brains were harvested for hippocampus neuron count and morphology study. Brains of the other 12 animals were harvested 24h after intervention to examine the expression of Akt, p-Akt, eNOS, p-eNOS, GSK-3\u03b2, p-GSK-3\u03b2 by Western bolting and mPTP opening.', 'Sevoflurane postconditioning significantly improved the long-term cognitive performance of the rats, increased the number of surviving neurons in CA1 and CA3 hippocampal regions, and protected the histomorphology of the left hippocampus. These effects were abolished by inhibitors of PI3K/eNOS/GSK-3\u03b2. Although blocking mPTP opening simulated sevoflurane postconditioning-induced neuroprotection, it failed to enhance it.",
            "output": [
                "Does sevoflurane postconditioning improve long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway?"
            ]
        },
        {
            "id": "task847-96231cad94614585832e34bf36b2e58e",
            "input": "Adipose tissue of obese subjects is known to exhibit increased inflammatory activity linked to altered expression of factors involved in glucose and lipid metabolism. The surgical procedure constitutes an injury per se, evoking a systemic inflammatory response.', 'To evaluate changes in the expression of key-genes in adipose tissue after common surgical procedures performed in obese patients.', 'A tertiary hospital.', 'Paired subcutaneous (SAT) and visceral (VAT) adipose tissue samples were collected at the beginning and the end of surgery in 33 obese patients that underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n = 17) or laparoscopic vertical sleeve gastrectomy (SG, n = 16). The expression of genes involved in inflammation, glucose and lipid metabolism was assessed.', 'The surgical procedure led to increased expression of interleukin 6, interleukin 8 (P<.0001 in both depots), tumor necrosis factor \u03b1 (P = .001 in SAT), and lipopolysaccharide binding protein (P = .0004 in VAT). Surgery also induced concomitant decreased expression of GLUT4, IRS1 (P = .046 in VAT), and adiponectin, whereas the messenger RNA of lipogenic genes [fatty acid synthase (P = .024); sterol regulatory element binding transcription factor 1 (P = .011) and aquaporin 9 (P<.0001) in SAT; and PPAR\u03b3 (P = .018) and solute carrier family 27 (fatty acid transporter), member 2 (P = .028) in VAT] increased in parallel to inflammation. Changes in gene expression during surgery were enhanced in patients following RYGB, when compared with SG.",
            "output": [
                "Does bariatric surgery acutely change the expression of inflammatory and lipogenic genes in obese adipose tissue?"
            ]
        },
        {
            "id": "task847-42fe5c94f17b4a2eb984091b3f27df62",
            "input": "This study aimed to compare the symptoms, unmet needs, and QoL reported by women at 6 months to <2 years and 2 to 5 years following surgery and adjuvant treatment for breast cancer. It also evaluated the relationships among symptoms, unmet needs, and QoL using structural equation modeling.', 'In this study, 113 and 137 survivors following breast cancer treatment 6 months to <2 years and 2 to 5 years, respectively, completed the Memorial Symptom Assessment Scale, the Supportive Care Needs Survey-34, and the Medical Outcomes Study 12-item Short Form Health Survey version 2.0 during their medical follow-up.', \"The mean numbers of symptoms and unmet needs were 5.43 and 3.0, respectively, for survivors at <2 years, and 5.24 and 2.42, respectively, for survivors at 2 to 5 years following treatment. The most common reported symptoms were related primarily to physical domains. No significant differences were found between the two survivor groups on the MSAS scores. Survivors at <2 years reported significantly higher scores in Psychological and Health Care System/Information needs (p\\u2009<\\u20090.01), and lower composite scores in physical and mental QoL (p\\u2009<\\u20090.05) than those at 2 to 5 years post-treatment. Significant direct and indirect effects were found of symptom burden through unmet needs on survivors' physical and mental QoL after adjustment for survival time, and the models showed a good fit.",
            "output": [
                "Do unmet needs mediate the relationship between symptoms and quality of life in breast cancer survivors?"
            ]
        },
        {
            "id": "task847-14a1e414d88b439c9226956d4dc1e9ca",
            "input": "Treatment of postoperative pain in children with cerebral palsy (CP) is a major challenge. We investigated the effect of epidural analgesia, high-volume local infiltration analgesia (LIA), and an approximated placebo control on early postoperative pain in children with CP who were undergoing unilateral hip reconstruction.', 'Between 2009 and 2014, we included 18 children with CP. The first part of the study was a randomized double-blind trial with allocation to either LIA or placebo for postoperative pain management, in addition to intravenous or oral analgesia. In the second part of the study, the children were consecutively included for postoperative pain management with epidural analgesia in addition to intravenous or oral analgesia. The primary outcome was postoperative pain 4 h postoperatively using 2 pain assessment tools (r-FLACC and VAS-OBS) ranging from 0 to 10. The secondary outcome was opioid consumption over the 21-h study period.', 'The mean level of pain 4 h postoperatively was lower in the epidural group (r-FLACC: 0.7; VAS-OBS: 0.6) than in both the LIA group (r-FLACC: 4.8, p\\u2009=\\u20090.01; VAS-OBS: 5.2, p\\u2009=\\u20090.02) and the placebo group (r-FLACC: 5.2, p\\u2009=\\u20090.01; VAS-OBS: 6.5, p\\u2009<\\u20090.001). Corrected for body weight, the mean opioid consumption was lower in the epidural group than in the LIA group and the placebo group (both p\\u2009<\\u20090.001).",
            "output": [
                "Is epidural analgesia superior to local infiltration analgesia in children with cerebral palsy undergoing unilateral hip reconstruction?"
            ]
        },
        {
            "id": "task847-7de0df7324fc45b68b7098adfbdc9da7",
            "input": "Pseudobulbar affect (PBA) is a neurological disorder of emotional expression, characterized by uncontrollable episodes of crying or laughing in patients with certain neurological disorders affecting the brain. The purposes of this study were to estimate the prevalence of PBA in US nursing home residents and examine the relationship between PBA symptoms and other clinical correlates, including the use of psychopharmacological medications.', 'A retrospective study was conducted between 2013 and 2014 with a convenience sample of residents from nine Michigan nursing homes. Chronic-care residents were included in the \"predisposed population\" if they had a neurological disorder affecting the brain and no evidence of psychosis, delirium, or disruptive behavior (per chart review). Residents were screened for PBA symptoms by a geropsychologist using the Center for Neurologic Study-Lability Scale (CNS-LS). Additional clinical information was collected using a diagnostic evaluation checklist and the most recent Minimum Data Set 3.0 assessment.', 'Of 811 residents screened, complete data were available for 804, and 412 (51%) met the criteria for the \"predisposed population.\" PBA symptom prevalence, based on having a CNS-LS score \u226513, was 17.5% in the predisposed population and 9.0% among all nursing home residents. Those with PBA symptoms were more likely to have a documented mood disorder and be using a psychopharmacological medication, including antipsychotics, than those without PBA symptoms.",
            "output": [
                "Do prevalence of pseudobulbar affect symptoms and clinical correlates in nursing home residents?"
            ]
        },
        {
            "id": "task847-a4386ff9fe304edcb81291291b840c97",
            "input": "Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB.', 'Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calcium mobilization in PBMCs of healthy individuals and TB patients by spectrofluorimetry, CD3 and CD28 induced activation of mitogen activated protein kinases (MAPKs) in PBMCs of healthy individuals and TB patients by western blotting and binding of transcription factors NFAT and NF\u03baB by Electrophorectic mobility shift assay (EMSA).', 'We observed CD3 triggered modulations in free intracellular calcium concentrations in PPD+ve healthy individuals and pulmonary TB patients after the treatment of M. tuberculosis antigens. As regards the downstream signalling events, phosphorylation of MAPKs, Extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 was curtailed by M. tuberculosis antigens in TB patients whereas, in PPD+ve healthy individuals only ERK1/2 phosphorylation was inhibited. Besides, the terminal signalling events like binding of transcription factors NFAT and NF\u03baB was also altered by M. tuberculosis antigens. Altogether, our results suggest that M. tuberculosis antigens, specifically ESAT-6, interfere with TCR/CD28-induced upstream as well as downstream signalling events which might be responsible for defective IL-2 production which further contributed in T-cell unresponsiveness, implicated in the progression of disease.",
            "output": [
                "Do mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events?"
            ]
        },
        {
            "id": "task847-66598981ce5c4ef486534d08c70303e7",
            "input": "Biochar is a solid coproduct of biomass pyrolysis, and soil amended with biochar has been shown to enhance the productivity of various crops and induce systemic plant resistance to fungal pathogens. The aim of this study was to explore the ability of wood biochar to induce resistance to the root-knot nematode (RKN) Meloidogyne graminicola in rice (Oryza sativa cv. Nipponbare) and examine its histochemical and molecular impact on plant defense mechanisms.', 'A 1.2 % concentration of biochar added to the potting medium of rice was found to be the most effective at reducing nematode development in rice roots, whereas direct toxic effects of biochar exudates on nematode viability, infectivity or development were not observed. The increased plant resistance was associated with biochar-primed H2O2 accumulation as well as with the transcriptional enhancement of genes involved in the ethylene (ET) signaling pathway. The increased susceptibility of the Ein2b-RNAi line, which is deficient in ET signaling, further confirmed that biochar-induced priming acts at least partly through ET signaling.",
            "output": [
                "Does biochar-amended potting medium reduce the susceptibility of rice to root-knot nematode infections?"
            ]
        },
        {
            "id": "task847-6d1b3d2d6e394566ae735c47c67ff1d5",
            "input": "Mdm4 negatively regulates the p53 tumor suppressor. Mdm4 loss in mice leads to an embryonic lethal phenotype that is p53-dependent. Biochemical studies indicate that Mdm4 also binds p73, a member of the p53 family, with higher affinity than p53. In this study, the significance of the Mdm4 and p73 interaction in vivo during embryogenesis and tumorigenesis was examined. The data revealed that p73 loss did not rescue either the early Mdm4-deficient embryonic lethality or the runted phenotype of Mdm4(\u03942/\u03942) p53(+/-) embryos. Furthermore, studies in the developing central nervous system wherein both genes have prominent roles indicated that loss of p73 also did not rescue the Mdm4-null brain phenotype as did p53 loss. This p53 dependency occurred despite evidence for p73-specific transcriptional activity. In tumor studies, the combination of Mdm4 overexpression and p73 loss did not alter survival of mice or the tumor spectrum as compared with Mdm4 overexpression alone. In summary, these data demonstrate that the Mdm4-p73 axis cannot override the dominant role of p53 in development and tumorigenesis.",
            "output": [
                "Does p53 Activity dominate That of p73 upon Mdm4 Loss in Development and Tumorigenesis?"
            ]
        },
        {
            "id": "task847-172d89ffcc604bed9beee8bea35621ca",
            "input": "It is widely accepted that chronic renal failure is associated with severe alterations of immune system. However, few studies looked into the immune alteration in earlier stage of chronic kidney disease (CKD) patients. To characterize immune defect in CKD patients, we performed lymphocyte subset analysis and explored its relationship to renal function in this population.', '472 CKD patients were enrolled in this study. Lymphocyte subsets (CD19(+), CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD56(+)CD16(+)) were determined by flow cytometry. Clinical and laboratory data were collected. Patterns of immune cells in different stages of CKD were compared. Multivariate linear regression was used to evaluate the relationship between lymphocyte subset group and renal function. Correlation analysis was used to assess the relationship between lymphocyte subset and other clinical and laboratory data.', 'Decreased lymphocyte counts occurred long before the end stage of renal disease. Increased NK cell percentage was negatively related to estimated glomerular filtration rate (eGFR) (r = -0.259, p < 0.001) while B cell percentage was positively related to eGFR (r = 0.249, p < 0.001). Further multivariate linear regression showed increased B cell percentage (\u03b2 = 16.470, 95%CI [1.018-31.922], p = 0.037) and decreased NK cell percentage (\u03b2 = -10.659, 95%CI [-20.063 to -1.254], p = 0.026) were independently correlated with higher eGFR, respectively. Patients with lower NK cell percentage and higher B cell percentage tended to have the best renal function.",
            "output": [
                "Do lymphocyte depletion and subset alteration correlate to renal function in chronic kidney disease patients?"
            ]
        },
        {
            "id": "task847-febc1c7a0bc84b64bf41b2b4efa72e06",
            "input": "To test the hypothesis that participants with stroke will exhibit appropriate increase in muscle activation of the paretic leg when taking a long step with the nonparetic leg compared to during steady-state walking, with a consequent increase in biomechanical output and symmetry during the stance phase of the modified gait cycle.', 'Single-session observational study.', 'Clinical research center in an outpatient hospital setting.', 'Adults with chronic poststroke hemiparesis (N=15).', 'Participants walked on an instrumented treadmill while kinetic, kinematic, and electromyogram data were recorded. Participants performed steady-state walking and a separate trial of the long-step adaptability task in which they were instructed to intermittently take a longer step with the nonparetic leg.', 'Forward progression, propulsive force, and neuromuscular activation during walking.', 'Participants performed the adaptability task successfully and demonstrated greater neuromuscular activation in appropriate paretic leg muscles, particularly increased activity in paretic plantarflexor muscles. Propulsion and forward progression by the paretic leg were also increased.",
            "output": [
                "Does locomotor Adaptability Task promote Intense and Task-Appropriate Output From the Paretic Leg During Walking?"
            ]
        },
        {
            "id": "task847-1a2adb9d9cc44ae083d2deb9fcd9e07b",
            "input": "Hedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown.', 'To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), anandamide (AEA), 2-AG, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) in 10 satiated severely obese subjects after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same bromatologic composition. Evaluation of hunger and satiety was also performed by visual analogic scale.', 'The anticipatory phase and the consumption of food for pleasure were associated with increased circulating levels of ghrelin, AEA, 2-AG, and OEA. In contrast, the levels of GLP-1, PYY, and PEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were higher and lower, respectively, in the hedonic session than in the non-palatable one.",
            "output": [
                "Are anticipatory and consummatory effects of ( hedonic ) chocolate intake associated with increased circulating levels of the orexigenic peptide ghrelin and endocannabinoids in obese adults?"
            ]
        },
        {
            "id": "task847-cd0cd737e827401b835d079652852f48",
            "input": "In developmental research, infants are commonly assumed to be early stakeholders in interactions with their caregivers. The tools that infants can use to interact with others vary from visual contact to smiling or vocalizing, and also include motor activity. However, surprisingly few studies have explored how the nature and context of social interactions affect infants' engagement in motor activity.\", \"We investigated the kinematic properties of foot and face movements produced by 11 infants aged between 5 and 9 months during six contrasting dyadic episodes (i.e. passive presence of a stranger or the infant's mother, weak or intense interaction with the stranger/mother as she sings a nursery play song).\", \"The infants' face and foot motor activity was significantly reduced during the interactive episodes, compared with the episodes without any interaction, in both the mother and stranger conditions. Furthermore, the level of their motor activity was significantly lower in the stranger condition than in the mother one for some parameters.",
            "output": [
                "Is social interaction associated with changes in infants ' motor activity?"
            ]
        },
        {
            "id": "task847-2ecd91f760004fc5b6fe3a0cb2b06758",
            "input": "fibromyalgia is a chronic disease characterized by generalized pain, stiffness, poor physical conditioning, non-restorative sleep and poor health-related quality of life. Ganoderma lucidum a type of mushroom that has demonstrated several benefits in different populations. Ceratonia siliqua is a natural therapy rich in antioxidants with potential benefits on health.', 'to evaluate the effects of 6-week treatment of Ganoderma lucidum and Ceratonia siliqua on physical fitness in patients suffering from fibromyalgia.', 'sixty-four women with fibromyalgia participated in the study. They took 6 g of Ganoderma lucidum or Ceratonia siliqua per day for 6 weeks. Different fitness tests were selected in order to evaluate functional capacity.', 'after the 6-week treatment period, Ganoderma lucidum significantly improved aerobic endurance, lower body flexibility, and velocity (p < .05). No significant improvement in any physical test was observed in the Ceratonia siliqua group.",
            "output": [
                "Does gANODERMA LUCIDUM improve PHYSICAL FITNESS IN WOMEN WITH FIBROMYALGIA?"
            ]
        },
        {
            "id": "task847-78eb13aa7e7c4a3bb2993f14d8130c80",
            "input": "Secondhand smoke (SHS) is a major risk factor for lung cancer in nonsmokers. DNA damage-derived mutagenicity is a well-established mechanism of SHS-carcinogenicity; however very little is known about the impact of SHS exposure on the epigenome.', 'We have investigated whether exposure to SHS can modulate the expression of key epigenetic regulators responsible for the establishment and/or maintenance of DNA methylation and histone modification patterns in vivo. We have sub-chronically exposed mice to a mutagenic but non-tumorigenic dose of SHS, and subsequently determined the expression levels of major epigenetic modifiers in the lungs of SHS-exposed mice, immediately after termination of exposure and following 7-month recovery in clean air.",
            "output": [
                "Is expression of epigenetic modifiers significantly altered by exposure to secondhand smoke?"
            ]
        },
        {
            "id": "task847-492708a4fa2f42b998ba8301d3e257f4",
            "input": "This study had investigated the anti-inflammatory activity of a seed lectin (LAL) isolated from Lonchocarpus araripensis.', 'LAL was purified by affinity chromatography (chitin column) and ion exchange chromatography (DEAE-Sephacel). In vitro LAL was tested for hemagglutinating activity against rabbit erythrocytes. In vivo LAL was assessed for the anti-inflammatory activity via intravenous injection (i.v.) in Swiss mice (25-30 g; n = 6/group) in models of paw edema and peritonitis.', 'ANOVA (p < 0.05).', 'LAL revealed two bands of 30 and 60 kDa (SDS-PAGE) and exhibited hemagglutinating activity. LAL (10 mg/kg) inhibited the paw edema (77%) and vascular permeability (26%) induced by carrageenan, and the paw edema induced by serotonin (80%), bradykinin (49%), sodium nitroprusside (83%), TNF-\u03b1 (75%) and PGE2 (64%). LAL also inhibited the neutrophil migration induced by fMLP (70%) or carrageenan (69%). The intravital microscopy showed that LAL inhibited rolling (83%) and adhesion (70%) of leukocytes. LAL anti-inflammatory effect was reversed by its association with N-acetyl-glucosamine. The nine-daily treatment with LAL (10 mg/kg; i.v.) showed no toxicity.",
            "output": [
                "Does a novel N-acetyl-glucosamine lectin of Lonchocarpus araripensis attenuate acute cellular inflammation in mice?"
            ]
        },
        {
            "id": "task847-7fe47960d5c64fc88a0bdb04179188c5",
            "input": "Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors.', 'Retrospective cohort study in a tertiary referral center in the UK.', 'A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow-up data.', 'Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact.",
            "output": [
                "Is mortality in patients with non-functioning pituitary adenoma increased : systematic analysis of 546 cases with long follow-up?"
            ]
        },
        {
            "id": "task847-650f5e2f8fb54fb9a5083b84d39a6d98",
            "input": "The efficacy of immunotherapy against advanced cancer may be improved by combination strategies. Photodynamic therapy (PDT) is a local tumor ablation method based on localized activation of a photosensitizer, leading to oxygen radical-induced tumor cell death. PDT can enhance antitumor immune responses by release of antigen and danger signals, supporting combination protocols of PDT with immunotherapy.', 'We investigated the local and systemic immune effects of PDT after treatment of established tumors. In two independent aggressive mouse tumor models, TC-1 and RMA, we combined PDT with therapeutic vaccination using synthetic long peptides (SLP) containing epitopes from tumor antigens.', 'PDT of established tumors using the photosensitizer Bremachlorin resulted in significant delay of tumor outgrowth. Combination treatment of PDT with therapeutic SLP vaccination cured one third of mice. Importantly, all cured mice were fully protected against subsequent tumor rechallenge, and combination treatment of primary tumors led to eradication of distant secondary tumors, indicating the induction of a systemic antitumor immune response. Indeed, PDT by itself induced a significant CD8(+) T-cell response against the tumor, which was increased when combined with SLP vaccination and essential for the therapeutic effect of combination therapy.",
            "output": [
                "Does combination of Photodynamic Therapy and Specific Immunotherapy Efficiently eradicate Established Tumors?"
            ]
        },
        {
            "id": "task847-2db8f013596b489d804357cc475ea98c",
            "input": "Open-wedge high tibial osteotomy (OWHTO) is a well-established procedure in the management of medial compartment osteoarthritis and osteonecrosis of the medial femoral condyle. Several studies have evaluated factors that negatively influence outcomes. However, few reports have investigated the effect of age on HTO outcome. We evaluated the influence of the age on the outcome after HTO.', 'The TomoFix', 'There were no statistical differences in the background factors between the two groups. Postoperatively, the mean JOA score showed a significant improvement in both groups. The mean OKS after surgery was 41.6\\xa0\u00b1\\xa05.9 in group A and 41.4\\xa0\u00b1\\xa05.9 in group B. There were no statistical differences in the postoperative knee alignment and clinical outcomes between the two groups.",
            "output": [
                "Does age affect the clinical and radiological outcomes after open-wedge high tibial osteotomy?"
            ]
        },
        {
            "id": "task847-1fa8aecb69cc4256bba71f52f973b6a9",
            "input": "The main objective of this study was to analyse the outcomes after total knee arthroplasty (TKA) of a group of patients with at least one self-reported allergy and a group of patients without reported allergies. We hypothesized there is a significant negative influence on clinical outcome scores after TKA in patients with self-reported allergies.', \"Four-hundred and seventy-five patients who had undergone TKA were analysed preoperatively and 1\\xa0year after surgery. The WOMAC, KSS and SF-36 scores were obtained. The patients' Yesavage depression questionnaire score was also recorded. The scores of the 330 (69.5\\xa0%) patients without self-reported allergies were compared to the scores of the 145 (30.5\\xa0%) patients with at least one self-reported allergy in the medical record.\", 'Preoperative scores were similar in both groups. The WOMAC post-operative scores (23.6 vs 20.4; p\\xa0=\\xa00.037) and the KSS-Knee score (91.1 vs 87.6; p\\xa0=\\xa00.027) were worse in the group of patients with self-reported allergies than in the group without allergies. The scores from the Yesavage depression questionnaire and in the SF-36 were similar in both groups.",
            "output": [
                "Do patient-reported allergies cause inferior outcomes after total knee arthroplasty?"
            ]
        },
        {
            "id": "task847-f64642499fcf481c80c65ecd58db05a7",
            "input": "Evaluate the cytotoxicity and genotoxicity of short- and long-term e-cigarette vapor exposure on a panel of normal epithelial and head and neck squamous cell carcinoma (HNSCC) cell lines.', 'HaCaT, UMSCC10B, and HN30 were treated with nicotine-containing and nicotine-free vapor extract from two popular e-cigarette brands for periods ranging from 48 h to 8 weeks. Cytotoxicity was assessed using Annexin V flow cytometric analysis, trypan blue exclusion, and clonogenic assays. Genotoxicity in the form of DNA strand breaks was quantified using the neutral comet assay and \u03b3-H2AX immunostaining.', 'E-cigarette-exposed cells showed significantly reduced cell viability and clonogenic survival, along with increased rates of apoptosis and necrosis, regardless of e-cigarette vapor nicotine content. They also exhibited significantly increased comet tail length and accumulation of \u03b3-H2AX foci, demonstrating increased DNA strand breaks.",
            "output": [
                "Do electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines?"
            ]
        },
        {
            "id": "task847-0bc6e75249044d92b2ae81c7c7384518",
            "input": "Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs that take part in occurrence and development of diabetes complication via regulating gene expression. However, litter is known about lncRNAs in the setting of diabetes induced nephropathy. The aim of this study was to examine whether lncRNA-myocardial infarction-associated transcript (MIAT) is involved in diabetes induced renal tubules injury.', 'Adult Wister rats were randomly assigned to receive intraperitoneal STZ (65\\xa0mg/kg) to induce diabetes. Rats treated with equal volume of citrate buffer were as control. Renal function was evaluated by analysis of serum creatinine and blood urea nitrogen (BUN) every four weeks after STZ administration. Also tubules of all rats were collected for determination of MIAT and Nrf2 level at the corresponding phase. The in\\xa0vitro high glucose-triggered human renal tubular epithelial cell line (HK-2) was used to explore the mechanism underling MIAT regulated high glucose-induced tubular damage.', 'In diabetic rats, MIAT showed the lower level and its expression is negatively correlated with serum creatinine and BUN. Consistent with diabetic rat, exposed to high glucose, HK-2 cells expressed lower level of MIAT and Nrf2, and also showed reduction in cell viability. By pcDNA-MIAT plasmid transfection, we observed that MIAT overexpression reversed inhibitory action of Nrf2 expression by high glucose. Moreover, the data of RNA pull-down and RIP showed that MIAT controlled Nrf2 cellular through enhancing Nrf2 stability, which was confirmed by CHX and MG132 administration. Inhibitory effect of cell viability by silencing MIAT was also reversed by Nrf2 overexpression.",
            "output": [
                "Does long non-coding MIAT mediate high glucose-induced renal tubular epithelial injury?"
            ]
        },
        {
            "id": "task847-b1a5780173d04730ac984880f6c4152e",
            "input": "Floral development can help to shed light on puzzling features across flowering plants. The enigmatic Amazonian monospecific genus Petaladenium of the legume family (Leguminosae) had rarely been collected and only recently became available for ontogenetic studies. The fimbriate-glandular wing petals of P. urceoliferum are unique among the more than 19000 legume species. Ontogenetic data illuminate the systematic position of the genus and foster our understanding on floral evolution during the early diversification of the papilionoid legumes.', 'Flower buds were collected in the field, fixed in 70% ethanol, and investigated using scanning electron microscopy (SEM). Results were compared with existing material from early-diverging papilionoid legumes.', 'Formation of sepals and petals shows bidirectional tendencies. Stamens arise in two whorls, and the single carpel arises concomitantly with the outer stamen whorl. Gland formation starts early on the edges of the wing petals. The carpel reopens for a short time when the initiation of ovules is visible. Stomata at the base of the hypanthium indicate that the flower functions like other standard flag blossoms.",
            "output": [
                "Do flowers of the early-branching papilionoid legume Petaladenium urceoliferum display unique morphological and ontogenetic features?"
            ]
        },
        {
            "id": "task847-86b2758cce9b4f5b84499c313f8210c0",
            "input": "Critical recurrences after radiofrequency ablation for hepatocellular carcinoma (HCC), such as intrahepatic metastases or dissemination, and extrahepatic metastases or seeding, which are difficult to treat radically, almost certainly lead to primary cancer death. The present study aimed to clarify whether the arterial tumor enhancement pattern on contrast-enhanced computed tomography (CECT) is associated with critical recurrence and cancer death after RFA for small HCC.', 'Between April 2001 and September 2011, 226 patients with initial small hypervascular HCC (\u22643 cm in diameter and \u22643 tumors) were treated by RFA. Arterial tumor enhancement patterns on CECT before RFA were categorized by whether non-enhanced areas were included inside the tumor stain.', 'The heterogeneous enhancement group included 44 patients, and the homogeneous enhancement group included 182 patients. The cumulative 5-year critical recurrence rates of the heterogeneous and homogeneous enhancement groups were 42 and 22% (p = 0.005), respectively. Univariate analysis for factors related to critical recurrence showed significant differences in sex, arterial enhancement pattern, and response to antiviral therapy. These factors were independent on multivariate analysis. The cumulative 5-year primary cancer death rates of the heterogeneous and homogeneous enhancement groups were 29 and 13% (p = 0.002), respectively. Univariate analysis for factors related to primary cancer death showed significant differences in arterial enhancement pattern and response to antiviral therapy. These factors were independent on multivariate analysis.",
            "output": [
                "Is the arterial tumor enhancement pattern on contrast-enhanced computed tomography associated with primary cancer death after radiofrequency ablation for small hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-d7264ea92ab641c29bbe69f692e7e7be",
            "input": "For many decades, the debate on children's competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children's competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children's competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives.",
            "output": [
                "Is informed consent instead of assent appropriate in children from the age of twelve : Policy implications of new findings on children 's competence to consent to clinical research?"
            ]
        },
        {
            "id": "task847-38df835ecc944819a45bd4a30b3e45e7",
            "input": "In patients presenting with a breast lesion, when initial core biopsy histology falls into the category of \"uncertain malignant potential\" (i.e. a B3 lesion), the next line of investigation has traditionally been a surgical biopsy (SBx). Vacuum-assisted biopsy (VAB) may be a viable minimally invasive alternative to SBx for B3 lesions. The primary aims of this study were to establish whether VAB reduces the need for surgical biopsy and determine VAB sensitivity for carcinoma following initial B3 histology.', 'B3 lesion data was collected from 2004 to 2013 retrospectively, from a single institution that utilises both VAB and SBx.', 'A total of 413 lesions were categorised B3 on initial biopsy. Mean age was 61 years (range: 24-91 years). Mean follow up was 52 months (range: 19-60 months). 156 patients (38%) underwent VAB. Only 20% of patients underwent VAB in 2004, with an increase to 95% by 2013. VAB histology revealed twelve carcinomas, all of which progressed to surgical excision. In six cases, a SBx was required following VAB in order to provide further diagnostic information. In one case, carcinoma was missed on VAB.",
            "output": [
                "Is vacuum-assisted biopsy a viable alternative to surgical biopsy in the investigation of breast lesions of uncertain malignant potential?"
            ]
        },
        {
            "id": "task847-2813529326444876959f34d01b27b1d3",
            "input": "While the anticholinergic activity of medications has been linked to cognitive decline, few studies have linked anticholinergic burden with falls in older people. We evaluated the relationship between anticholinergic burden and recurrent and injurious falls among community-dwelling older adults.', 'This case-control study was performed on 428 participants aged \u226565 years, 263 cases with two or more falls or one injurious fall in the preceding 12 months, and 165 controls with no falls in the preceding 12 months. Anticholinergic burden was determined using the anticholinergic cognitive burden (ACB) scale. Upper and lower limb functional abilities were assessed with timed up and go (TUG), functional reach (FR) and grip strength (GS). Logistic regression analysis was employed to calculate the mediation effect of TUG, FR and GS on ACB associated falls.', 'Univariate analysis revealed a significant association between an ACB score of \u22651 with falls (OR, 1.8; 95% CI; 1.1-3.0; p=0.01) and significantly poorer TUG and FR. The association between ACB\u22651 and falls was no longer significant after adjustment for either TUG (OR for ACB associated falls, 1.4; 95% CI, 0.88-2.4; p=0.14) or FR (OR for ACB associated falls, 1.4; 95% CI, 0.89-2.4, p=0.12) but remained significant with GS.",
            "output": [
                "Is anticholinergic burden associated with recurrent and injurious falls in older individuals?"
            ]
        },
        {
            "id": "task847-84c0497fa46048e6bdb30de0a2853845",
            "input": "We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT).', 'Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K(trans), and the fraction of blood plasma volume, Vp. The temporal changes in the means of hippocampal transfer constant K(trans) and Vp after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT.', 'The mean K(trans) Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=-0.95, P<.0006) and 18-months (r=-0.88, P<.02) post-RT.",
            "output": [
                "Does a Radiation-Induced Hippocampal Vascular Injury Surrogate Marker predict Late Neurocognitive Dysfunction?"
            ]
        },
        {
            "id": "task847-073ba1ba19864e02bc2254be9ced96f8",
            "input": "Human insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate. This study investigated whether human insulin use might be associated with breast cancer risk in Taiwanese women with type 2 diabetes.', 'The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,033 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the adjusted hazard ratios were estimated by Cox regression. The potential risk modification by concomitant treatment with metformin, statin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) was also evaluated.', 'There were 59,798 ever-users and 422,235 never-users of human insulin, with respective numbers of incident breast cancer of 559 (0.93 %) and 4,711 (1.12 %), and respective incidence of 207.9 and 215.1 per 100,000 person-years. The overall adjusted hazard ratio (95 % confidence interval) did not show a significant association with insulin [1.033 (0.936-1.139)]. However, patients in the third tertiles of dose-response parameters might show a significantly higher risk of breast cancer while compared to never-users: 1.185 (1.026-1.368), 1.260 (1.096-1.450) and 1.257 (1.094-1.446) for \u226567 months for time since starting insulin, \u226539,000 units for cumulative dose of insulin, and \u226521.8 months for cumulative duration of insulin, respectively. Additional analyses suggested that the breast cancer risk associated with human insulin use might be beneficially modified by concomitant use of metformin, statin and ACEI/ARB.",
            "output": [
                "Does prolonged use of human insulin increase breast cancer risk in Taiwanese women with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-975deb7bd65440f29cb5f099471759aa",
            "input": "The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed clear cell A (ccA) and clear cell B (ccB). The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34.', 'In this retrospective analysis, 282 patients from Moffitt Cancer Center with ccRCC with gene expression analyses of the primary tumor were identified and ClearCode34 was applied to identify tumors as ccA or ccB. The medical record and institutional databases were queried to define patient characteristics, comorbidities, and outcomes.', 'We validated in this external cohort the superior overall survival, cancer-specific survival, and recurrence-free survival of ccA patients relative to ccB patients (P<0.001). Addressing other clinical characteristics, the ccA patients were more likely to be obese (48% vs. 34%, P = 0.021) and diabetic (26% vs. 13%, P = 0.035). The ccA patients also trended toward having been more frequent users of angiotensin system inhibitors (71% vs. 52%, P = 0.055). In multivariate analyses, ccB status is independently associated with inferior cancer-specific survival (hazard ratio = 3.26, 95% confidence interval: 1.84-5.79) and overall survival (hazard ratio = 2.50, 95% confidence interval: 1.53-4.08).",
            "output": [
                "Do patients with ClearCode34-identified molecular subtypes of clear cell renal cell carcinoma represent unique populations with distinct comorbidities?"
            ]
        },
        {
            "id": "task847-dcdde15e2afa4b0abb946e16897a62c0",
            "input": "To investigate the differential expressions of nucleolin in invasive cervical squamous cell carcinoma, cervical intraepithelial neoplasms (CIN) and normal cervical epithelial tissues and explore the role of nucleolin in the carcinogenesis and progression of cervical squamous cell carcinoma.', 'Fifty specimens of invasive cervical squamous cell carcinoma, 65 specimens of CIN, and 60 adjacent normal cervical epithelial tissue specimens were examined immunohistochemically for nucleolin expression. The correlation of nucleolin expression levels with histological grades of invasive cervical squamous cell carcinoma and CIN were analyzed.', 'The specimens of invasive cervical squamous cell carcinoma showed a significantly higher positivity rate for nucleolin expression than CIN and normal cervical epithelial tissues, and the rate in CIN tissues was significantly higher than that in normal cervical epithelial tissues (P<0.01). The expression level of nucleolin was significantly higher in invasive cervical squamous cell carcinoma than in CIN and normal cervical epithelia tissues, and higher in CIN than in normal cervical epithelia tissues, whose immunostaining scores were 7.6\u00b10.3, 6.1\u00b10.2, and 3.0\u00b10.2, respectively (P<0.01). The mean nucleolin immunostaining score was significantly higher in poorly and moderately differentiated than in highly differentiated cervical squamous cell carcinoma (7.9 vs 7.1, P<0.01), and higher in high grade CIN than in low grade CIN tissues (6.0 vs 4.0, P<0.01).",
            "output": [
                "Is [ Nucleolin expression correlated with carcinogenesis and progression of cervical squamous cell carcinoma ]?"
            ]
        },
        {
            "id": "task847-f47b98b8f3454184a9911d95fb5749d2",
            "input": "The aim of this study was to evaluate post-tetanic potentiation of muscle twitch in myasthenia gravis (MG).', 'Post-tetanic potentiation was evaluated by recording the compound muscle action potential (CMAP) of abductor pollicis brevis and movement-related potential (MRP) of the thumb using an accelerometer after tetanic stimulation of the median nerve at the wrist. After baseline recording, tetanic stimulation was delivered to the median nerve at a frequency of 10 Hz for 10s. The CMAP and MRP were successively recorded at baseline and at 5, 10, 30, 60, 90 and 120 s after tetanic stimulation. The chronological changes of CMAPs and MRPs were recorded bilaterally in 11 patients with MG, 9 patients with myopathies (disease controls), and 25 healthy control subjects.', 'Maximal acceleration of MRP was significantly elevated during 10s after tetanic stimulation without any CMAP changes in all groups. However, statistical analysis detected a significant decrease in post-tetanic potentiation of maximal acceleration of MRP in MG patients only compared to healthy controls, but not in myopathy patients, which may imply impairment of excitation-contraction coupling in MG.",
            "output": [
                "Do impaired post-tetanic potentiation of muscle twitch in myasthenia gravis?"
            ]
        },
        {
            "id": "task847-e763e8905e2d4353abab545740a3247b",
            "input": "The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy.', 'We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-A\u03b225-35-injected mice, and the potential mechanisms.', 'AChE activity assay, intracellular Ca(2+) content and calcium currents measurement, and A\u03b225-35-induced cellular death determine were performed for validation of designed targets and neuroprotection of SCR-1693. Mice were orally administrated with SCR-1693 once daily after an A\u03b225-35 injection. The Morris water maze and Y-maze test, and hippocampal protein detection were conducted on days 5-10, day 11, and day 8. The pyramidal neuron number, hippocampal AChE activity, and synaptic transmission were measured on day 12.', 'SCR-1693 acted as a selective, reversible, and noncompetitive inhibitor of AChE, and a nonselective voltage-gated calcium channel blocker. SCR-1693 also inhibited the increase of AChE activity in the mouse hippocampus. SCR-1693 was more effective than donepezil and memantine in preventing A\u03b225-35-induced long-term and short-term memory impairment, maintaining the basal transmission of Schaffer collateral-CA1 synapses, and sustaining LTP in mouse hippocampus. SCR-1693 attenuated A\u03b225-35-induced death of SH-SY5Y cell and the loss of hippocampal pyramidal neurons, and regulated A\u03b225-35-induced signal cascade in neurons.",
            "output": [
                "Does a novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improve A\u03b225-35-impaired mouse cognitive function?"
            ]
        },
        {
            "id": "task847-06e6d2b7a6de448ebb3d90710f262441",
            "input": "Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs.', 'Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression.', 'We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001).",
            "output": [
                "Is rANK/OPG ratio of expression in primary clear-cell renal cell carcinoma associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs?"
            ]
        },
        {
            "id": "task847-1da5ec4e83944bdbb0d4f2c2b0f5510d",
            "input": "Our previous studies show that \u03b22-adrenergic receptor (\u03b22-AR) is highly expressed in most Her2-overexpressing breast cancers. However, the mechanisms underlying upregulation of the \u03b22-AR expression in Her2-overexpressing breast cancer cells are not fully understood. The clinical significance of the \u03b22-AR overexpression in breast cancer is unclear.', 'Human breast cancer cells MCF-7 and MCF-7/Her2 were transfected with the let-7 mimics or inhibitors. The expression of \u03b22-AR was analyzed by Western blot. The \u03b22-AR status in primary and metastatic sites of breast cancer and the human breast cancer tissue microarrays containing 49 primary tumors and 50 metastatic lymph node tissues was analyzed by immunohistochemistry. The correlation of lymph node metastasis with the \u03b22-AR level was determined in 59 primary tumor tissues from the patients with Her2-positive breast cancer. The clinical prognostic significance of the \u03b22-AR overexpression in the patients with Her2-positive breast cancers was evaluated by a retrospective study.', 'The let-7f level in Her2-overexpressing breast cancer cells SKBR3 and BT474 was significantly lower than that in MCF-7 cells, which express low level of Her2. Ectopic expression of Her2 in MCF-7 cells (MCF-7/Her2) represses the expression of microRNA let-7f, which is previously identified to regulate baseline \u03b22-AR expression. The treatment with MEK1/2 inhibitors PD98059 or PD184352 effectively restored the let-7f level, suggesting that Her2-overexpression-mediated ERK constitutive activation inhibited let-7f, leading to the upregulation of the \u03b22-AR expression. The transfection with the let-7f mimics markedly downregulated the \u03b22-AR level, whereas the let-7 inhibitor significantly upregulated the \u03b22-AR expression in both parental MCF-7 and MCF-7/Her2 cells. In addition, treatment of MCF-7/Her2 cells with isoproterenol resulted in a concentration-dependent reduction of the let-7f expression, demonstrating that the inhibitory effect of Her2 overexpression on let-7f can be reinforced by agonist-triggered \u03b22-AR activation. We further demonstrate that high level of \u03b22-AR associates with lymph node metastasis and poor outcome in the patients with Her2-positive breast cancer.",
            "output": [
                "Does a Her2-let-7-\u03b22-AR circuit affect prognosis in patients with Her2-positive breast cancer?"
            ]
        },
        {
            "id": "task847-0b189334ca8b4a998c011fbe192a0da8",
            "input": "To investigate the mutation status of growth differentiation factor 15 (GDF15) in patients with oral squamous cell carcinoma (OSCC), as well as the prognostic value of missense GDF15 mutations.', 'Formalin-fixed paraffin-embedded biopsy samples from 46 OSCC patients were involved in this study. GDF15 and TP53 mutations were sequenced using the Ion Torrent Personal Genome Machine, GDF15 protein expression was detected using immunohistochemistry. Torrent Suite Software v.3.6, Integrative Genomics Viewer; v.2.3, statistical software SPSS18.0 for Windows were used for analysis. All hypothesis-generating tests were two-sided at a significance level of 0.05.', 'Twenty-nine GDF15 mutations were identified in 19 out of 46 patients (41.3%), including eighteen missense mutations, two nonsense mutations and nine synonymous mutations. The patients with missense GDF15 mutations had poorer prognostic outcomes than those with wild-type GDF15, including overall survival (P = 0.035), disease-free survival (P = 0.032), locoregional recurrence-free survival (P = 0.015), and distant metastasis-free survival (P = 0.070). Missense GDF15mutations was an independent increased risk factor of overall survival (HR = 5.993, 95% CI:1.856-19.346, P = 0.003), disease-free survival (HR = 3.764, 95% CI:1.295-10.945, P = 0.015), locoregional recurrence-free survival (HR = 4.555, 95% CI:1.494-13.889, P = 0.008), and distant metastasis-free survival (HR = 4.420, 95% CI:1.145-13.433, P = 0.009).",
            "output": [
                "Does mutant GDF15 present a poor prognostic outcome for patients with oral squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-2594d11dda2b41b09aea7579ae7913c2",
            "input": "Hydrogen sulfide (H2S) exhibits protective effects in various disease models including cerebral ischemia-reperfusion (I/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H2S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H2S, mediates protective effects of an H2S donor compound sodium sulfide (Na2S) against neuronal I/R injury.', 'We observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na2S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral I/R injury. Beneficial effects of STS, as well as Na2S, were associated with marked increase of thiosulfate, but not H2S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating \"carrier\" molecule of beneficial effects of H2S. Protective effects of thiosulfate were associated with inhibition of caspase-3 activity by persulfidation at Cys163 in caspase-3. We discovered that an SLC13 family protein, sodium sulfate cotransporter 2 (SLC13A4, NaS-2), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na2S and STS.",
            "output": [
                "Does thiosulfate mediate Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia?"
            ]
        },
        {
            "id": "task847-ecde9c14300b4adabd637acff2fd2ee5",
            "input": "This study was designed to assay the expression of zinc finger protein X-linked (ZFX) in renal cell carcinoma (RCC) tissues and evaluate the correlation between ZFX expression and prognosis of RCC patients.', 'The expressions of ZFX mRNA in 53 RCC tissues and 51 normal tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) technology was used to measure the expression of ZFX protein. Then chi-square test was conducted to verify the association between ZFX expression and clinical parameters. Next, we explored the overall survival rate of RCC patients with Kaplan-Meier analysis. Finally, the correlation between ZFX expression and the prognosis of RCC patients was evaluated by Cox regression analysis.', 'The qRT-PCR result showed that the ZFX was significantly up-regulated in RCC tissues. As for the IHC consequence, the positive rate of ZFX expression in RCC specimens was 79.2%, while that in the normal control tissues was only 17.6%. Chi-square test showed that ZFX expression shared no close relationship with age, sex, or smoking (P>0.05), but was tightly associated with TNM stage, tumor size, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with ZFX positive expression had higher mortality than those with negative expression (P<0.05). Cox regression analysis revealed that ZFX expression had tight correlation with prognosis of RCC patients (HR=4.997, P=0.045, 95%CI=1.033-24.180).",
            "output": [
                "Is zFX a Strong Predictor of Poor Prognosis in Renal Cell Carcinoma?"
            ]
        },
        {
            "id": "task847-fdc9c4bd8f1d4e218302e1e90fb7a68d",
            "input": "The purpose of the present study was to evaluate the detection rate of genomic aberrations in haematological malignancies using oligobased array-CGH (oaCGH) analysis in combination with karyotyping and fluorescence in situ hybridization (FISH) analyses, and its feasibility in a clinical pragmatic approach.', 'The 4x180K Cancer Cytochip array was applied in 96 patients with various haematological malignancies in a prospective setting and in 41 acute myeloid leukemia (AML) patients retrospectively.', 'Combined use of oaCGH analysis and karyotyping improved the overall detection rate in comparison to karyotyping-alone and vice versa. In cases with normal karyotypes oaCGH analysis detected genomic aberrations in 66% (39/60) of cases. In the group of simple karyotypes oaCGH analysis extended karyotypic findings in 39% (12/31) while oaCGH analysis extended the karyotypic findings in 89% (39/44) of cases with complex karyotypes. In 7% (5/75) of cases oaCGH analysis failed in detecting the observed abnormalities by karyotyping.",
            "output": [
                "Does oligo-based High-resolution aCGH Analysis enhance Routine Cytogenetic Diagnostics in Haematological Malignancies?"
            ]
        },
        {
            "id": "task847-8ee9e79e570d4a6f94971594e1059136",
            "input": "This work aimed to identify altered pathways in congenital heart defects (CHD) in Down syndrome (DS) by systematically tracking the dysregulated modules of reweighted protein-protein interaction (PPI) networks.', 'We performed systematic identification and comparison of modules across normal and disease conditions by integrating PPI and gene-expression data. Based on Pearson correlation coefficient (PCC), normal and disease PPI networks were inferred and reweighted. Then, modules in the PPI network were explored by clique-merging algorithm; altered modules were identified via maximum weight bipartite matching and ranked in non-increasing order. Finally, pathways enrichment analysis of genes in altered modules was carried out based on Database for Annotation, Visualization, and Integrated Discovery (DAVID) to study the biological pathways in CHD in DS.', 'Our analyses revealed that 348 altered modules were identified by comparing modules in normal and disease PPI networks. Pathway functional enrichment analysis of disrupted module genes showed that the 4 most significantly altered pathways were: ECM-receptor interaction, purine metabolism, focal adhesion, and dilated cardiomyopathy.",
            "output": [
                "Does systematic Tracking of Disrupted Modules identify Altered Pathways Associated with Congenital Heart Defects in Down Syndrome?"
            ]
        },
        {
            "id": "task847-f47fd9d6114e46fc94c97191771ca773",
            "input": "The aim of this study was to evaluate antioxidant and cytoprotective effects of iloprost and Vitamin C in a distant organ after abdominal aorta ischemia-reperfusion injury.', 'Twenty-eight New Zealand rabbits weighing 2,400-2,800 g were used for this study. The rabbits were divided into four equal groups. These groups are control group, sham group, iloprost group, and iloprost+vitamin C group. Suprarenal aorta was occluded with a vascular clamp. Following 30 minutes of ischemia, the vascular clamp was removed. Rabbits in group 3 received 10 ng/kg/min iloprost and those in group 4 received 10 ng/kg/min iloprost and 10 mg/kg vitamin C. At the end of the reperfusion period, the rabbits were sacrificed by a high intraperitoneal dose of xylazine+ketamine injection. Myocardial tissue samples were taken for electron microscopic analysis. We evaluated SOD, MDA and catalase in myocardial tissue samples.', 'Iloprost and iloprost+vitamin C groups significantly reduced the oxidative stress markers in tissue samples (p<0.05) and significantly decreased the myofibrillar injury and mitochondrial morphology changes in the myocardial tissue as shown with electron microscopy (p<0.05). Myocardial edema was significantly alleviated by iloprost and iloprost+vitamin C administration (p<0.05).",
            "output": [
                "Does iloprost and vitamin C attenuate acute myocardial injury induced by suprarenal aortic ischemia-reperfusion in rabbits?"
            ]
        },
        {
            "id": "task847-995e0e7cd4714ef0b00ba6dac7c9aedd",
            "input": "Pain intensity attenuates muscular activity, proprioception, and tactile acuity, with consequent changes of joint kinematics. People suffering from low back pain (LBP) frequently show movement control impairments of the lumbar spine in sagittal plane. This cross-sectional, observational study investigated if the intensity of LBP attenuates lumbar movement control. The hypothesis was that lumbar movement control becomes more limited with increased pain intensity.', 'The effect of LBP intensity, measured with a numeric rating scale (NRS), on lumbar movement control was tested using three movement control tests. The lumbar range of motion (ROM), the ratio of lumbar and hip ROM as indicators of direction specific movement control, and the recurrence and determinism of repetitive lumbar movement patterns were assessed in ninety-four persons suffering from LBP of different intensity and measured with an inertial measurement unit system. Generalized linear models were fitted for each outcome.', 'Lumbar ROM (+ 0.03\u00b0, p = 0.24) and ratio of lumbar and hip ROM (0.01, p = 0.84) were unaffected by LBP intensity. Each one point increase on the NRS resulted in a decrease of recurrence and determinism of lumbar movement patterns (-3.11 to -0.06, p \u2a7d 0.05).",
            "output": [
                "Does pain intensity attenuate movement control of the lumbar spine in low back pain?"
            ]
        },
        {
            "id": "task847-2c14da8480ff46c5ab98deb154596e69",
            "input": "Currently there is no reliable medical treatment for aortic regurgitation (AR).', 'Thirty-nine Sprague-Dawley rats underwent creation of AR or sham operation. Treated rats were assigned to early or late institution of sildenafil therapy (100\\xa0mg/kg/day) for a total of 10\\xa0weeks. Treatment-effects were measured by serial echocardiography, invasive hemodynamic measurements, and tissue analysis.', 'Rats assigned to early treatment developed less remodeling than untreated rats. Thus, left ventricular (LV) dilation was blunted by sildenafil with end-systolic diameter being significantly smaller (6.6\\xa0\u00b1\\xa00.4 vs. 7.7\\xa0\u00b1\\xa00.4\\xa0mm, respectively, p\\xa0<\\xa00.05). Also, LV wall thickness was significantly decreased in treated rats compared to controls (2.23\\xa0\u00b1\\xa00.08 vs. 2.16\\xa0\u00b1\\xa00.05\\xa0mm, p\\xa0<\\xa00.01). Fractional shortening was improved by treatment (p\\xa0<\\xa00.05). Myocardial fibrosis was borderline decreased by treatment (p\\xa0=\\xa00.09). Akt was increased in treated compared to controls (p\\xa0<\\xa00.05).",
            "output": [
                "Does sildenafil treatment attenuate ventricular remodeling in an experimental model of aortic regurgitation?"
            ]
        },
        {
            "id": "task847-b3e0bf27e8b649d3b20ba8cb09b18437",
            "input": "Obesity-associated insulin resistance (IR) is highly correlated with soluble tumor necrosis factor-\u03b1 (sTNF-\u03b1), which is released from transmembranous TNF-\u03b1 by TNF-\u03b1 converting enzyme (TACE). In vivo, TACE activity is suppressed by tissue inhibitor of metalloproteinase 3 (TIMP3). Agents that can interact with TACE/TIMP3 to improve obesity-related IR would be highly valuable. In the current study, we assessed whether (2S,3R,4S)-4-hydroxyisoleucine (4-HIL) could modulate TACE/TIMP3 and ameliorate an obesity-induced IR-like state in 3T3-L1 adipocytes.', '3T3-L1 adipocytes were incubated in the presence of 25 mM glucose and 0.6 nM insulin to induce an IR-like state, and were then treated with different concentrations of 4-HIL or 10 \u00b5M pioglitazone (positive control). The glucose uptake rate was determined using the 2-deoxy-[(3)H]-D-glucose method, and the levels of sTNF-\u03b1 in the cell supernatant were determined using ELISA. The protein expression of TACE, TIMP3, and insulin signaling-related molecules was measured using western blotting.', 'Exposure to high glucose and insulin for 18 hours increased the levels of sTNF-\u03b1 in the cell supernatant. The phosphorylation of insulin receptor substrate-1 (IRS-1) Ser(307) and Akt Ser(473) was increased, whereas the protein expression of IRS-1, Akt, and glucose transporter-4 was decreased. The insulin-induced glucose uptake was reduced by 67% in 3T3-L1 adipocytes, which indicated the presence of an IR-like state. The above indexes, which demonstrated the successful induction of an IR-like state, were reversed by 4-HIL in a dose-dependent manner by downregulating and upregulating the protein expression of TACE and TIMP3 proteins, respectively.",
            "output": [
                "Does 4-Hydroxyisoleucine ameliorate an insulin resistant-like state in 3T3-L1 adipocytes by regulating TACE/TIMP3 expression?"
            ]
        },
        {
            "id": "task847-268b4addb4314292aa0fa677b10bc00a",
            "input": "The dietary determinants of adolescent blood pressure (BP) are not well understood. We determined the association between major dietary patterns and BP in a sample of Iranian adolescents.', \"This cross-sectional study was conducted among a representative sample (n\\xa0=\\xa0557) of Shirazi adolescents aged 12-19\\xa0years. Participants' systolic and diastolic BP was measured using a validated oscillometric BP monitor. Usual dietary intakes during the past 12\\xa0months were assessed using a valid and reproducible 168-item semiquantitative food frequency questionnaire through face-to-face interviews. Principal component factor analysis was used to identify major dietary patterns based on a set of 25 predefined food groups.\", 'Overall, three major dietary patterns were identified, among which only the Western pattern (abundant in soft drinks, sweets and desserts, salt, mayonnaise, tea and coffee, salty snacks, high-fat dairy products, French fries, and red or processed meats) had a significant association with BP. After adjusting for potential confounders in the analysis of covariance models, multivariable adjusted means of the systolic and mean BP of subjects in the highest tertile of the Western pattern score were significantly higher than those in the lowest tertile (for systolic BP: mean difference 6.9\\xa0mmHg, P\\xa0=\\xa00.001; and for mean BP: mean difference 4.2\\xa0mmHg, P\\xa0=\\xa00.003). A similar but statistically insignificant difference was observed in terms of diastolic BP.",
            "output": [
                "Is a Western dietary pattern associated with higher blood pressure in Iranian adolescents?"
            ]
        },
        {
            "id": "task847-875cc1605d6048bfaa11fdcd596ef16a",
            "input": "The epithelial-mesenchymal transition (EMT) is the process where cells lose their epithelial features and acquire properties of typical mesenchymal cells. The dissociation of tumor cells due to changes in cell-cell adhesion is one of the key principles of tumor invasion and EMT. Thus, the knowledge of the molecular features of EMT in keratocyst odontogenic tumor (KOT) can provide useful markers to aid in the diagnosis and prognosis and perhaps contribute to an alternative therapeutic approach as it shows an aggressive clinical behavior and high recurrence rates. This study aimed to evaluate the EMT in KOT by the immunoexpression of E-cadherin, N-cadherin, Snail, and Slug and comparing to radicular cysts and dental follicles.', 'Thirty-two KOTs, 15 radicular cysts, and 08 dental follicles were used for immunohistochemistry, evaluating the extent, intensity, labeling pattern, cellular compartment in the epithelium and stroma, and the presence of inflammation.', 'E-cadherin was preserved in most cases of keratocystic odontogenic tumor. N-cadherin was increased in the tumor epithelium, a result that was positively correlated with the heterogeneous and nuclear immunoexpression of Slug in the epithelium; Slug also correlated with high Snail immunoexpression. N-cadherin was positively correlated with Slug in the stroma of keratocystic odontogenic tumors.",
            "output": [
                "Are e-cadherin regulators differentially expressed in the epithelium and stroma of keratocystic odontogenic tumors?"
            ]
        },
        {
            "id": "task847-8587565e42984046a6ee947fdbc21591",
            "input": "Interstitial cells of Cajal (ICC) have been shown to be present in the extrahepatic biliary tract of animals and humans. However, ICC distribution in choledochal cysts (CC) has not been investigated. A study was conducted to investigate the distribution of ICC in the extrahepatic biliary tract, including CC, in pediatric human specimens.', 'The specimens were divided into two main groups as gallbladders and common bile ducts. Gallbladders were obtained from the cholelithiasis, CC operations and autopsies. Common bile ducts were obtained from autopsies. Tissues were stained using c-kit immunohistochemical staining. ICC were assessed semi-quantitatively by applying morphological criteria and were counted as the number of cells/0.24 mm(2) in each area under light microscopy.', 'A total of 35 gallbladders and 14 CC were obtained from operations. Ten gallbladders plus common bile ducts were obtained from autopsies. The mean numbers of ICC in the gallbladders of cholelithiasis and the gallbladders of CC were 12.2 \u00b1 4.9 and 5.3 \u00b1 1.2, respectively (p = 0.003). The mean numbers of ICC in the common bile ducts and CC were 9.8 \u00b1 2.9 and 3.4 \u00b1 1.4, respectively (p = 0.001).",
            "output": [
                "Does the Density of Interstitial Cells of Cajal be Diminished in Choledochal Cysts?"
            ]
        },
        {
            "id": "task847-831873a82a7246719901e6bb7811d5eb",
            "input": "Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers.', 'To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival.', 'Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses.', 'High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival.",
            "output": [
                "Is nerve Growth Factor Expression Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma?"
            ]
        },
        {
            "id": "task847-ca7538954b2f48dcabb9e05c6d17d16c",
            "input": "Thyroid cancer stem cells (CSCs) with ALDH and CD44 markers contribute to tumor growth and aggressiveness. We hypothesized that novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG can effectively target the function of thyroid CSCs in vitro and prevent migration and invasion.', 'Validated papillary (TPC1), follicular (FTC238,WRO), and anaplastic (ACT1) human thyroid cancer cell lines were treated with 3 HSP90 inhibitors. CSCs were quantified for aldehyde dehydrogenase by flow cytometry, CD44 expression by Western blot, and thyrosphere formation assay. Cellular pathway proteins were analyzed by Western blot and migration/invasion by Boyden-chambers.', 'WGA-TA and 17-AAG induced HSP70 compensation (not observed with KU711) on Western blot in all cell lines (>1,000 fold vs controls). Only WGA-TA degraded HSP90-Cdc37 complexing by 60-70% versus controls. Expression of HSP90 clients \u03b2-catenin, BRAF, Akt, and phospho-Akt were significantly inhibited by WGA-TA treatment (50-80%, 50-90%, >80%, and >90%) compared with controls, KU711, and 17-AAG treatment. KU711 and WGA-TA decreased CD44 expression in all cell lines (25-60% vs controls/17-AAG), decreased ALDEFLOR activity by 69-98% (P < .005), and decreased sphere formation by 64-99% (P < .05 each). Finally, cell migration was decreased by 31-98%, 100%, and 30-38%, and invasion by 75-100%, 100%, and 47% by KU711,WGA-TA, and 17-AAG treatment (P < .05) each, respectively.",
            "output": [
                "Do novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion?"
            ]
        },
        {
            "id": "task847-5ae5df26deb4470f9833f6a3539091f6",
            "input": "Increased progesterone level during follicular phase seemed to be associated with decreased pregnancy rate.', 'A prospective cohort study, 1.1.2012 - 31.8.13. The Progesterone (P) and Progesterone/Estrogen (P/E2) level on ovulation induction day were compared between the protocols and the different gonadotropins used. Roc analysis was calculated to determine the cutoff of P/E2 to predict delivery rates. P/E2 ratio was calculated as PX1000/e2 level.', 'One hundred thirty-nine patients were enrolled to the study. No difference in the P level at hCG stimulation day between different protocols, however, E2 and P/E2 ratio were significantly lower in the long protocol compare with antagonist protocol 1757.7\\u2009\u00b1\\u2009923.2 vs. 1342.9\\u2009\u00b1\\u20091223; P\\u2009=\\u20090.003 and 0.48\\u2009\u00b1\\u20090.31 vs. 0.83\\u2009\u00b1\\u20090.87; P\\u2009=\\u20090.038). The endometrium was significantly thicker in the long group compare with short and antagonist. Significantly more top-quality embryos (TOP) were achieved in the antagonist group. Comparable results between the types of gonadotropins used in regards with cycle characteristics and pregnancy and delivery rates. The P/E2 ratio which can predict live birth rate was found to be 0.45, AUC\\u2009=\\u20090.632, p\\u2009=\\u20090.02 and 95\\xa0% CI 0.525-0.738 and a significantly higher pregnancy and delivery rates at a P/E2 bellow 0.45.",
            "output": [
                "Is late follicular progesterone to estradiol ratio influenced by protocols or gonadotropins used?"
            ]
        },
        {
            "id": "task847-7e90d94a2a064708a5f0ce4011113e8d",
            "input": "Coagulation Factor XIII (FXIII) plays an important role in wound healing by stabilizing fibrin clots and cross-linking extracellular matrix proteins. FXIII is expressed in cells of the monocyte/macrophage and dendritic cell lineages in response to type 2 cytokines.', 'We sought to determine the association between FXIII and asthma pathobiology.', 'We analyzed the expression of FXIII mRNA and protein levels in bronchoalveolar lavage samples obtained before and after segmental allergen challenge from patients with mild asthma and in induced sputum samples collected from patients with mild-to-moderate and severe asthma.', 'FXIII mRNA and protein levels were highly upregulated in bronchoalveolar cells and fluid after allergen challenge and mRNA levels correlated with protein levels. In sputum of asthmatic patients, FXIII expression was positively correlated with type 2 immune response and dendritic cell markers (CD209 and CD207). FXIII expression was also associated with increased airflow limitation (FEV1/forced vital capacity and residual volume/total lung capacity ratios) and greater reversibility to \u03b2-agonists.",
            "output": [
                "Does airway factor XIII associate with type 2 inflammation and airway obstruction in asthmatic patients?"
            ]
        },
        {
            "id": "task847-cef6ba42a27147189d8af059d59b7d7a",
            "input": "Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown.', 'To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients.', 'In a pilot study, eight patients with low HDL (\u2264 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI.', 'Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells.",
            "output": [
                "Does [ Nicotinic acid increase cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia ]?"
            ]
        },
        {
            "id": "task847-edce33dfed0d462ab6d5b875738d3939",
            "input": "This study was performed to examine the association between household food insecurity, self-efficacy and infant feeding styles in mothers with children under 2 years old in Varamin, Iran.', \"In this cross-sectional study, 423 mothers aged 17-40 years from different areas of Varamin were selected by a multistage sampling methods from October 2013 to February 2014. The questionnaires consisted of three valid instruments, including: Household Food Insecurity Access Scale, Comprehensive Feeding Practices Questionnaire and Mother's Self-Efficacy Questionnaire. Data were analyzed using Chi-square, t tests, ANOVA, Pearson correlations and multiple linear regressions. Structural equation modeling was also used.\", \"Mild and moderate-severe food insecurity was observed in 39.5 and 12.8 % of the households respectively. Mean score of mother's self-efficacy in food secure households was 32.5 \u00b1 3.7; while in mild food insecure and moderate-severe food insecure households were 31.9 \u00b1 3.1 and 28.4 \u00b1 4.0, respectively (P = 0.001). There was a significant negative correlation between household food insecurity and mother's self-efficacy (r = -0.297, P < 0.01). Significant correlation was seen between mother's self-efficacy and the maternal infant feeding styles. Household food insecurity and mother's self-efficacy had significant relationship with mother-infant feeding styles: control of home food access [\u03b2 (SE)] = [-0.015(0.004), P = 0.001]; restriction for weight control [\u03b2 = 0.038(0.013), P = 0.003]; restriction for health [\u03b2 = 0.019(0.008), P = 0.027] and encouragement [=0.018(0.006), P = 0.001]. The model had sufficient fitness with data of the research (CFI = 0.927, RMSEA = 0.076).",
            "output": [
                "Does mother 's Self-Efficacy mediate the Relationship Between Household Food Insecurity and Maternal Infant Feeding Styles?"
            ]
        },
        {
            "id": "task847-0632e3d76dd24566b68f5dcb5277357a",
            "input": "FGF receptor (FGFR) family can be activated by FGFs and play important roles in regulating cell growth, differentiation, migration and angiogenesis. Recent studies suggested that FGFR4 could regulate several processes including tumor progression. Nasopharyngeal carcinoma (NPC) is a malignancy with a high occurrence in Southeast Asia and Southern China. However, the molecule mechanism and the potential roles of FGFR4 in NPC remain unknown Methods: Immunohistochemistry and western blot were used to investigate the expression of FGFR4 in NPC samples. Then we used statistical analysis to evaluate the diagnostic value and the associations of FGFR4 expression with clinical parameters. In vitro studies, the effects of FGFR4 on proliferation and migration of NPC cell line CNE2 were measured by the starvation-refeeding experiment, CCK8 assay, wounding healing assay and transwell migration assay. The changes of the epithelial-mesenchymal transition (EMT) markers in CNE2 cells after knocking down the expression of FGFR4 were measured by Western blot and immunofluorescence analysis.', 'FGFR4 was overexpressed in NPC as compared with the inflammatory tissues. High expression of FGFR4 was correlated with Ki67 expression, clinical stages and prognosis in NPC patients (P<0.05).While in vitro, the upregulation of FGFR4 was accompanied with CNE2 cells released from serum starvation. Moreover, it could increase cell proliferation and migration by regulating EMT markers in CNE2 cells.",
            "output": [
                "Does high Expression of FGFR4 enhance Tumor Growth and Metastasis in Nasopharyngeal Carcinoma?"
            ]
        },
        {
            "id": "task847-af0ea137f33d4b9596902c9686f4b096",
            "input": "Follicular lymphoma (FL) frequently develops drug-resistance and transforms into more aggressive subtypes over time. It is urgent to find prognostic biomarkers and disclose signaling pathways that have potential to be drug targets. In this study, we investigated the association of FL prognosis with the expression of 2 proteins: PIK3CD, a PI3K pathway component, and CD9, a tetraspanin family member.', 'The expression of PIK3CD and CD9 were examined on 76 FL tumor tissues and 15 normal tissues with Immunohistochemistry. Chi-square test, Cox proportional hazards model, and Kaplan-Meier estimates were used to analyze the relationships of CD9 and PIK3CD expression and major clinicopathological features.', 'PIK3CD expression was significantly higher, whereas CD9 expression was significantly lower in the 76 FL specimens than normal tissues. Concomitantly, low CD9 or high PIK3CD expression is associated with high degrees of Ann Arbor stages. In agreement with this, PIK3CD is an unfavorable and CD9 is a favorable factor for progression-free survival (PFS). Interestingly, PIK3CD expression is negatively correlated with CD9 expression, and the PIK3CD-high/CD9-low was significantly associated with short PFS when the 2 factors were combined together. Lastly, CD9 expression was significant higher in patients with bone marrow infiltration (BMI) than those without BMI.",
            "output": [
                "Is the Expression of CD9 and PIK3CD Associated with Prognosis of Follicular Lymphoma?"
            ]
        },
        {
            "id": "task847-f51b93ce3e1244e990029a2c45ce3bb8",
            "input": "Among hemodialysis patients, probing dry weight is an effective strategy for improving control of hypertension. Whether controlling hypertension improves or worsens symptoms among such patients remains unclear. The purpose of the study was to develop a tool to evaluate symptoms and examine the relationship of the change in these symptoms with blood pressure (BP) control.', 'Among patients participating in the Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) randomized controlled trial, a confirmatory factor analysis (CFA) was performed to establish the relationship between symptoms and organ systems. Next, the change in symptom scores pertaining to organ systems was analyzed using a mixed model. Finally, the independent effect of lowering home BP on change in symptoms was evaluated.', 'Among 133 participants where symptoms were available at baseline, CFA revealed four level 1 domains: gastrointestinal symptoms, dialysis-related symptoms, cardiovascular symptoms and general symptoms. All except dialysis-related symptoms were ascribed to uremia (level 2 domain). Uremic symptoms improved over 6 months and then increased. Dialysis-related symptoms (fatigue, cramps and orthostatic dizziness) did not worsen despite lowering home BP. Probing dry weight was independently associated with an improvement in cardiovascular symptoms such as shortness of breath.",
            "output": [
                "Does treating hypertension in hemodialysis improve symptoms seemingly unrelated to volume excess?"
            ]
        },
        {
            "id": "task847-e3206e36457944969125df94de524cc7",
            "input": "Aberrancies in gene expression in immune effector cells and in end-organs are implicated in lupus pathogenesis. To gain insights into the mechanisms of tissue injury, we profiled the expression of micro-RNAs in inflammatory kidney lesions of human lupus nephritis (LN).', 'Kidney specimens were from patients with active proliferative, membranous or mixed LN and unaffected control tissue. Micro-RNAs were quantified by TaqMan Low Density Arrays. Bioinformatics was employed to predict gene targets, gene networks and perturbed signaling pathways. Results were validated by transfection studies (luciferase assay, real-time PCR) and in murine LN. Protein expression was determined by immunoblotting and immunohistochemistry.', 'Twenty-four micro-RNAs were dysregulated (9 up-regulated, 15 down-regulated) in human LN compared with control renal tissue. Their predicted gene targets participated in pathways associated with TGF-\u03b2, kinases, NF-\u03baB, HNF4A, Wnt/\u03b2-catenin, STAT3 and IL-4. miR-422a showed the highest upregulation (17-fold) in active LN and correlated with fibrinoid necrosis lesions (\u03b2 = 0.63, P = 0.002). In transfection studies, miR-422a was found to directly target kallikrein-related peptidase 4 (KLK4) mRNA. Concordantly, KLK4 mRNA was significantly reduced in the kidneys of human and murine LN and correlated inversely with miR-422a levels. Immunohistochemistry confirmed reduced KLK4 protein expression in renal mesangial and tubular epithelial cells in human and murine LN.",
            "output": [
                "Does micro-RNA analysis of renal biopsies in human lupus nephritis demonstrate up-regulated miR-422a driving reduction of kallikrein-related peptidase 4?"
            ]
        },
        {
            "id": "task847-02dadef1ea8545fb8f14577e290852bc",
            "input": "Porphyromonas gingivalis infection induces apoptosis inhibition in gingival epithelial cells; however, it is not fully understood which bacterial effectors are involved in this process. The aim of this study is to evaluate whether the P.\\xa0gingivalis lipopolysaccharide (LPS), specifically the O-antigen region, affects adherence, invasion, viability and apoptosis of gingival epithelial cells.', \"Gingival epithelial cells (OKF6/TERT2 line) were infected by different freshly prepared P.\\xa0gingivalis clinical isolates, obtained from subjects with chronic periodontitis (CP3 and CP4) and healthy individuals (H1 and H3). Periodontitis and healthy isolates show differences in O-antigen production, as healthy isolates lack the O-antigen region. In addition, cells were infected by a site-specific mutant lacking the O-antigen portion. After 24\\xa0h postinfection, cell proliferation, viability and apoptosis were evaluated by Trypan blue, MTS and annexin V assays, respectively. Bacterial invasion, adhesion and proliferation were measured by gentamicin/metronidazole protection assays. Finally, toll-like receptor (TLR)2 and TLR4 mRNA expression was evaluated by quantitative reverse transcription-polymerase chain reaction. Statistical analysis was performed using ANOVA, Tukey's or Dunnett's tests (p\\xa0<\\xa00.05).\", 'At 24\\xa0h postinfection, strains lacking the O-antigen region (healthy isolates and O-antigen ligase-deficient strain) were unable to increase proliferation and viability, or decrease apoptosis as compared with strains producing intact LPS (periodontitis isolates and reference strain). However, the presence of the O-antigen neither contributed to changes in the ability of the bacteria to adhere to or invade cells, nor to intracellular survival. The presence of O-antigen also increased the expression of TLR4 (nearly sixfold), which correlated with inhibition of apoptosis.",
            "output": [
                "Is the Porphyromonas gingivalis O antigen required for inhibition of apoptosis in gingival epithelial cells following bacterial infection?"
            ]
        },
        {
            "id": "task847-3e3154fab0d34204af518abc3d6db886",
            "input": "Enhanced processing of emotional stimuli after stress exposure is reported to be associated with stress-induced cortisol. Because enhanced emotional information processing could make cognitive emotion regulation more difficult, it was hypothesized that stress-induced cortisol would be associated with non-negative interpretation generation associated with the cognitive reappraisal processes.', 'A total of 36 participants (Mean age\\u2009=\\u200921.3\\xa0years, SD\\u2009=\\u20091.8) watched video clips of depression-related stressful situations before and after the administration of a stress induction task. They were then asked to generate as many non-negative interpretations as possible to reduce the depressive mood. Saliva samples were obtained before and after the stress induction task to measure change in the cortisol level.', 'Participants were allocated post-hoc to either a responder (n\\u2009=\\u200919) or non-responder group (n\\u2009=\\u200917) based on the cortisol response to the stress induction task. The number of non-negative interpretations generated following the stress induction task was reduced only in the cortisol responders. The number of post-stress non-negative interpretations was fewer in the responder group when compared by sex, baseline cortisol level, and the number of pre-stress non-negative interpretations, statistically controlled.",
            "output": [
                "Is stress-induced cortisol associated with generation of non-negative interpretations during cognitive reappraisal?"
            ]
        },
        {
            "id": "task847-125ff8d41ff345b396f6fdc46f3c21c8",
            "input": "A number of countries have banned misleading cigarette descriptors such as \"light\" and \"low-tar\" as called for by the WHO Framework Convention on Tobacco Control. These laws, however, do not address the underlying cigarette design elements that contribute to misperceptions about harm. This is the first study to examine beliefs about \"light\" cigarettes among Korean smokers, and the first to identify factors related to cigarette design that are associated with the belief that \"light\" cigarettes are less harmful.', 'We analysed data from Wave 3 of the ITC Korea Survey, a telephone survey of a nationally representative sample of 1,753 adult smokers, conducted October - December 2010. A multinomial logistic regression was used to examine which factors were associated with the belief that \"light\" cigarettes are less harmful than regular cigarettes.', 'One quarter (25.0 %) of smokers believed that \"light\" cigarettes are less harmful than regular cigarettes, 25.8 % believed that smokers of \"light\" brands take in less tar, and 15.5 % held both of these beliefs. By far the strongest predictor of the erroneous belief that \"light\" cigarettes are less harmful was the belief that \"light\" cigarettes are smoother on the throat and chest (p\\u2009<\\u20090.001, OR\\u2009=\\u200944.8, 95 % CI 23.6-84.9).",
            "output": [
                "Are the importance of the belief that `` light '' cigarettes smoother in misperceptions of the harmfulness of `` light '' cigarettes in the Republic of Korea : a nationally representative cohort study?"
            ]
        },
        {
            "id": "task847-cb69b3173029484fb3bdc2aba89083dc",
            "input": "To investigate whether single nucleotide polymorphisms (SNP) of drug transporter proteins for TDF is a risk factor for TDF-related renal function decrement.', \"This study investigated the association between 3 SNPs (ABCC2-24, 1249, and ABCB1 2677), which are shown to be associated with TDF-induced tubulopathy, and clinically important renal outcomes (>10ml/min/1.73m2 decrement in eGFR relative to baseline, >25% decrement in eGFR, and eGFR <60ml/min/1.73m2) in 703 HIV-1-infected Japanese patients who initiated TDF-containing antiretroviral therapy (ART). Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays.\", '95% of the study patients were males and 66% were treatment-na\u00efve, with median CD4 count of 249/\u03bcl, median baseline eGFR of 96ml/min/1.73m2 (IQR 84.6-109.2), and median exposure to TDF of 3.66 years (IQR 1.93-5.59). The frequencies of genotypes at -24, 1249 of ABCC2, and 2677 of ABCB1 were neither different between patients with decrement in eGFR of >10ml/min/1.73m2 and those without such decrement (ABCC2: -24, p = 0.53, 1249, p = 0.68; ABCB1: 2677, p = 0.74), nor between those without and with the other two renal outcomes (>25% decrement: ABCC2: -24, p = 0.83, 1249, p = 0.97, ABCB1: 2677, p = 0.40; eGFR <60ml/min/1.73m2: ABCC2: -24, p = 0.51, 1249, p = 0.81, ABCB1: 2677, p = 0.94). Logistic regression analysis showed that the risk genotype of the three SNPs were not associated with any of the three renal outcomes, respectively. Logistic regression model that applied either dominant, recessive, or additive model yielded the same results.",
            "output": [
                "Are drug Transporter Genetic Variants Associated with TDF-Related Renal Dysfunction in Patients with HIV-1 Infection : A Pharmacogenetic Study?"
            ]
        },
        {
            "id": "task847-4faecbb14ab44de994bb7f334896eb28",
            "input": "Most knee joint biomechanics studies have involved knees with an isolated anterior cruciate ligament (ACL) injury. However, a large portion of patients with injured ACLs have accompanied meniscus tearing. In this study, the in vivo alteration of knee biomechanics after tearing the ACL with or without combined medial or lateral meniscus tear was investigated during stair-ascending activity.', 'The kinematic behavior of ACL-deficient knees changes with a combined medial or lateral meniscus tear.', 'Controlled laboratory study.', 'Twenty-one patients with injured ACLs (contralateral side intact) were recruited before undergoing ACL reconstruction. Among these patients, 5 had isolated ACL injuries (group I), 8 had combined ACL and medial meniscus injuries (group II), and 8 had combined ACL and lateral meniscus injuries (group III). Bilateral magnetic resonance scans were obtained on each patient to construct 3-dimensional anatomic knee models. Both knees were then scanned during stair-climbing activity using a dual fluoroscopic imaging system. The knee kinematics during stair climbing were reproduced using a bone model image matching method. Anteroposterior and mediolateral translations and axial tibial rotation of the knee during stair ascent were then compared between the injured and intact contralateral knees of the patients.', 'On average, injured knees in groups I and III showed more than 2 mm increased anterior tibial translation close to full knee extension. In group II, no statistically significant difference was observed between the injured and contralateral side in anteroposterior translation. Near full extension, in groups I and III, injured knees had less than 1 mm of increased medial tibial translation compared with the contralateral side, whereas in group II, a 1.0-mm increase in lateral tibial shift was observed in the injured knees. With regard to axial tibial rotation, group I showed an increased external tibial rotation (approximately 5\u00b0), group II had little variation, whereas group III had increased internal tibial rotation (approximately 3\u00b0).",
            "output": [
                "Do meniscus Injuries Alter the Kinematics of Knees With Anterior Cruciate Ligament Deficiency?"
            ]
        },
        {
            "id": "task847-4c41f7bea920469083945a98c2fef74b",
            "input": "Aspirin (ASA) causes gastrotoxicity by hampering the epithelial defense against luminal contents through cyclooxygenase\\xa0inhibition. Since cell survival in tough conditions may depend on rescue mechanisms like autophagy, we analyzed whether epithelial cells rely on this process to defend themselves from aspirin's damaging action.\", 'Rats received a single dose of ASA (150\\xa0mg/kg, p.o.) with or without pretreatment with the autophagy inhibitor 3-methyladenine, and gastric injury and epithelial autophagy were evaluated 3\\xa0h later. The effects of ASA on cell viability and autophagy were also evaluated in gastric epithelial AGS cells.', 'Basal autophagy in the gastric mucosa was inhibited by ASA as demonstrated by increased levels of p62 and ubiquitinated proteins and total LC3 and a reduced LC3-II/LC3-I ratio. Similarly, ASA increased p62 and decreased LC3-II accumulation and the number of EmGFP/LC3B puncta in AGS cells. ASA activated the PI3K/Akt-GSK3-mTOR pathway, which phosphorylates ULK1 to prevent autophagy initiation, changes that were inhibited by the PI3K-inhibitor wortmannin. Autophagy inhibition seems to enhance the vulnerability of gastric epithelial cells as a combination of ASA with 3-methyladenine exacerbated rat gastric damage and AGS cell apoptosis.",
            "output": [
                "Is aspirin-induced gastrointestinal damage associated with an inhibition of epithelial cell autophagy?"
            ]
        },
        {
            "id": "task847-3d449671a18749f08561d6e814bd8c10",
            "input": "Network component analysis (NCA) became a popular tool to understand complex regulatory networks. The method uses high-throughput gene expression data and a priori topology to reconstruct transcription factor activity profiles. Current NCA algorithms are constrained by several conditions posed on the network topology, to guarantee unique reconstruction (termed compliancy). However, the restrictions these conditions pose are not necessarily true from biological perspective and they force network size reduction, pruning potentially important components.', 'To address this, we developed a novel, Iterative Sub-Network Component Analysis (ISNCA) for reconstructing networks at any size. By dividing the initial network into smaller, compliant subnetworks, the algorithm first predicts the reconstruction of each subnetwork using standard NCA algorithms. It then subtracts from the reconstruction the contribution of the shared components from the other subnetwork. We tested the ISNCA on real, large datasets using various NCA algorithms. The size of the networks we tested and the accuracy of the reconstruction increased significantly. Importantly, FOXA1, ATF2, ATF3 and many other known key regulators in breast cancer could not be incorporated by any NCA algorithm because of the necessary conditions. However, their temporal activities could be reconstructed by our algorithm, and therefore their involvement in breast cancer could be analyzed.",
            "output": [
                "Does iterative sub-network component analysis enable reconstruction of large scale genetic networks?"
            ]
        },
        {
            "id": "task847-f0935b78896842faaf139c7ddad41941",
            "input": "SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin-Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders.', 'We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression.', 'We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin-Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly.",
            "output": [
                "Are deletions and de novo mutations of SOX11 associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome?"
            ]
        },
        {
            "id": "task847-11540e84de994fbfacd518dd5455254b",
            "input": "Accumulation of tumor-infiltrating mast cells (MCs) predicts poor survival in several cancers after resection. However, its effect on the prognosis of patients with colorectal liver metastases (CRLM) is not known.', 'Our retrospective study included 135 patients who underwent potentially curative resection for CRLM between 2001 and 2010. Expression of tryptase, MAC387, CD83, and CD31, which are markers for MCs, macrophages, mature dendritic cells, and vascular endothelial cells, respectively, was determined via immunohistochemistry of resected tumor specimens. The relationship between immune cell infiltration and long-term outcome was investigated.', 'The median follow-up time was 48.4 months for all patients and 57.5 months for survivors. Overall survival (OS) rates at 1, 3, and 5 years were 91.0, 62.4, and 37.4 %, respectively. Five-year disease-free survival (DFS) and OS rates were 21.6 and 38.1 %, respectively, in patients with high MC infiltration, and 42.6 and 55.6 %, respectively, in patients with low MC infiltration (p\\u2009<\\u20090.01 for both DFS and OS). Infiltration of other types of immune cells did not correlate with survival. Multivariate analyses indicated that hypoalbuminemia and high peritumoral MC infiltration were significant predictors of unfavorable OS.",
            "output": [
                "Does high infiltration of mast cells positive to tryptase predict worse outcome following resection of colorectal liver metastases?"
            ]
        },
        {
            "id": "task847-fe589b83d2b448878a4d2e303e5ef35b",
            "input": "Weight gain after kidney transplantation (Tx) is considered a risk factor for poor outcomes. Increased oxidative stress is associated with not only chronic renal disease and Tx, but also obesity and cardiovascular disease. The aim of this pilot study was to test whether oxidative stress is related to weight gain at 12-months after kidney Tx and to obtain preliminary insight into potential mechanisms involved.', 'Recipients (n=33) were classified into two groups; weight loss and weight gain, based on their weight changes at 12-months post-transplant. Total antioxidant capacity (TAOC) and lipid peroxidation (TBARS) were measured to evaluate oxidative stress from plasma at baseline and 12-months. A secondary data analysis was conducted to identify potential gene regulation.', 'Seventeen recipients lost (-6.63\u00b15.52kg), and sixteen recipients gained weight (8.94\u00b16.18kg). TAOC was significantly decreased at 12-months compared to baseline for the total group, however, there was no significant difference between groups at either time point. TBARS was higher in weight gain group, at both time points, and it was significantly higher at 12-months (p=0.012). Gene expression profiling analysis showed that 7 transcripts annotated to reactive oxygen species related genes in adipose tissue were expressed significantly lower in weight gain group at baseline, which might be a negative feedback mechanism to reduce oxidative stress.",
            "output": [
                "Is oxidative stress associated with weight gain in recipients at 12-months following kidney transplantation?"
            ]
        },
        {
            "id": "task847-925a7322b3b144ee9d2db3532195cc97",
            "input": "In Australia, adult immunisation coverage is primarily monitored via periodic telephone surveys that rely on self-reported immunisation status. All Australian residents are eligible for Medicare, so we examined the feasibility of using immunisation-specific Medicare Benefits Schedule (MBS) item numbers to monitor and estimate adult influenza immunisation coverage.', 'Baseline questionnaire data from 267 129 participants from the 45 and Up Study, a prospective cohort study, were linked to data containing information on individual MBS immunisation-specific items from 2006 to 2011. Temporal trends in recording of these items were examined. Self-reported influenza immunisation status obtained from a follow-up questionnaire from 27 036 participants was then compared with the MBS immunisation records.', 'From 2006 to 2011, the pattern of MBS immunisation claims was consistent with self-reported influenza immunisation trends, with annual peaks occurring from March to May. There was fair agreement between MBS immunisation records and self-reported influenza immunisation: 48.8% (95% CI 47.1, 50.4) of participants who self-reported influenza immunisation had a matching MBS record, and 79.6% (95% CI 78.8, 80.4) who reported never having influenza immunisation had no matching MBS record. However, compared with self-reported influenza vaccination for people aged \u226565 years from the 2009 Adult Immunisation Telephone Survey (74.6%), the proportion of participants aged >65 years with an MBS immunisation record was low, with an annual median of 39.3% (range 28.3%-62.1%).",
            "output": [
                "Do medicare Benefits Schedule data to monitor influenza immunisation in Australian adults?"
            ]
        },
        {
            "id": "task847-09ddfc34ec0b42858ab9755db814eb00",
            "input": "Ovarian cancer is the most lethal gynecologic malignancy, with limited treatment options for chemoresistant disease. An important link between inflammation and peritoneal spread of ovarian cancer is NF-\u03baB signaling. Thymoquinone (TQ) exerts multiple anti-tumorigenic cellular effects, including NF-\u03baB inhibition. We aimed to investigate the therapeutic potential of TQ in an established murine syngeneic model of ovarian cancer.', 'ID8-NGL mouse ovarian cancer cells stably expressing an NF-\u03baB reporter transgene were injected intra-peritoneally into C57BL/6 mice, and mice were treated with TQ or vehicle for 10 or 30\\xa0days. TQ was combined with the macrophage depleting drug, liposomal clodronate, in selected experiments. Effects on peritoneal tumor burden were measured by volume of ascites, number of peritoneal implants and mesenteric tumor mass. NF-\u03baB reporter activity and markers of proliferation and apoptosis were measured in tumors and in confirmatory in vitro experiments. Protein or mRNA expression of M1 (anti-tumor) and M2 (pro-tumor) macrophage markers, and soluble cytokine profiles, were examined from harvested ascites fluid, peritoneal lavages and/or tumor sections. 2-tailed Mann-Whitney tests were used for measuring differences between groups in in vivo experiments.', 'Consistent with its effects in vitro, TQ reduced proliferation and increased apoptosis in ID8-NGL tumors after 10 and 30\\xa0day treatment. Prolonged TQ treatment did not significantly alter tumor number or mass compared to vehicle, but rather exerted an overall deleterious effect by stimulating ascites formation. Increased ascites was accompanied by elevated NF-\u03baB activity in tumors and macrophages, increased pro-tumor M2 macrophages and expression of pro-tumorigenic soluble factors such as VEGF in ascites fluid, and increased tumor infiltration of M2 macrophages. In contrast, a 10\\xa0day exposure to TQ produced no ascites, and reduced tumor NF-\u03baB activity, M2 macrophages and soluble VEGF levels. Peritoneal macrophage depletion by clodronate significantly reduced tumor burden. However, TQ-stimulated ascites was further enhanced by co-treatment with clodronate, with macrophages present overwhelmingly of the M2 phenotype.",
            "output": [
                "Do microenvironmental effects limit efficacy of thymoquinone treatment in a mouse model of ovarian cancer?"
            ]
        },
        {
            "id": "task847-057308da12c644db8561543b081e9200",
            "input": "Tadalafil can restore endothelial function and treat atherosclerosis. However, the effect of tadalafil on transplant arteriosclerosis remains unclear. In this study, we explore the effects of tadalafil on allograft vasculopathy.', 'Male Brow-Norway rats supplied aorta grafts for Male Lewis rats. All recipients were divided into 3 groups: saline as placebo (control) treated group, low dose tadalafil (0.5 mg/kg/day) treated group, and high dose tadalafil (1.0 mg/kg/day) treated group. Eight weeks after transplantation, the grafts were harvested at and analyzed by histological and Western blot analysis. An enzyme-linked immunosorbent assay (ELISA) was used for measure of plasma cyclic guanylate monophosphate (cGMP).', 'the treatment with tadalafil significantly alleviated the neointimal thickness of aortas compared with the control group (P<0.05). Tadalafil also remarkably enhanced the production of cGMP in plasma and expression of cGMP-dependent kinase I (PKG-I) and RhoA compared with control group (P<0.05).",
            "output": [
                "Does tadalafil attenuate graft arteriosclerosis of aortic transplant in a rat model?"
            ]
        },
        {
            "id": "task847-26706bc1850742e69e4fce6afa7c1db7",
            "input": "We aimed to investigate outcomes of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) for the removal of large pancreatic stones coexisting with pancreatic pseudocysts (PPCs) in chronic pancreatitis (CP).', 'This is a prospective study performed in CP patients with at least 1 stone (\u22655\\xa0mm). Patients were divided into the PPC group (stones coexisting with PPCs) or the control group (stones alone). Patients were initially subjected to successive P-ESWL treatments, followed by ERCP. Primary outcomes were P-ESWL adverse events, and secondary outcomes were stone clearance, long-term pain relief, improved quality-of-life scores, and PPC regression.', 'A total of 849 patients (59 in the PPC group and 790 in the control group) was subjected to P-ESWL between March 2011 and October 2013. Occurrences of P-ESWL adverse events were similar between the PPC\\xa0group and the control group (11.86% vs 12.41%, P\\xa0= .940). After the treatment of initial P-ESWL combined with ERCP, the complete, partial, and nonclearance of stones occurred in 67.24%, 20.69%, and 12.07%, respectively, of patients in PPC group, with no significant difference from the control group (complete, partial, and nonclearance: 83.17%, 10.40%, and 11.39%, respectively; P\\xa0= .106). Fifty-five of 59 patients (93.22%) with PPCs were followed for a median period of 21.9 months (range, 12.0-45.1). PPCs disappeared in 56.36% (31/55) and 76.36% (42/55) of patients after 3 months and 1 year of follow-up visits, respectively. Moreover, complete and partial pain relief were achieved in 63.64% (35/55) and 25.45% (14/55) of patients, respectively. The scores for quality of life (P\\xa0< .001), physical health (P\\xa0< .001), and weight loss (P\\xa0< .001) improved.",
            "output": [
                "Is extracorporeal shock wave lithotripsy a safe and effective treatment for pancreatic stones coexisting with pancreatic pseudocysts?"
            ]
        },
        {
            "id": "task847-94fb69538f6d47c49a35198b8e59ff68",
            "input": "To determine the incidence, characteristics, and outcomes associated with geographical miss (GM) of plaque.', 'GM describes plaques that are incompletely covered following stenting, with GM thought to be associated with worse clinical outcomes. However, the incidence and characteristics of intravascular ultrasound (IVUS)-defined GM plaques have never been studied and the relationship between GM with both short and long-term clinical events is unknown.', 'One hundred and seventy patients with stable angina (n\\u2009=\\u2009100) or myocardial infarction (MI) (n\\u2009=\\u200970) underwent virtual-histology IVUS (VH-IVUS) prior to, and following, percutaneous coronary intervention (PCI). GM was defined as three consecutive uncovered VH frames, either proximal or distal to the stented segment with plaque burden >40%. MACE was defined as a composite of death, myocardial infarction, unplanned revascularization, or hospitalization for angina.', 'In total, 245 plaques underwent PCI with 80 (32.7%) displaying evidence of GM (69 patients). GM was associated with increased plaque volume (p\\u2009<\\u20090.001), % necrotic core, and dense calcium (both p\\u2009<\\u20090.001) and VH-defined thin-cap fibroatheroma (VH-TCFA) (p\\u2009=\\u20090.01). GM was not associated with increased periprocedural MI (p\\u2009=\\u20090.15) or inflammatory cytokine release. At follow-up, 42 MACE occurred in 28 patients (median 1,115 days). MACE was attributable to 8/80 (10%) plaques with and 7/165 (4.2%) plaques without GM (log-rank p\\u2009=\\u20090.11). GM was associated with increased MACE in patients presenting with MI (p\\u2009=\\u20090.015), but not for those with stable angina (p\\u2009=\\u20090.94).",
            "output": [
                "Do geographical miss is associated with vulnerable plaque and increased major adverse cardiovascular events in patients with myocardial infarction?"
            ]
        },
        {
            "id": "task847-c5a0233dc1a5465fb4a334353f97575b",
            "input": "Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia.\", 'One hundred and twenty-one cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), A\u03b2 plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined.', 'The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, P < 0.001). The total cortical A\u03b2 plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (P = 0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE \u03f54 allele was associated with a higher cortical LB burden (P = 0.02), particularly in the neocortical frontal, parietal and temporal regions.",
            "output": [
                "Are cortical Lewy bodies and A\u03b2 burden associated with prevalence and timing of dementia in Lewy body diseases?"
            ]
        },
        {
            "id": "task847-4340a7f51f6f453385f6c9ec0a15bc55",
            "input": "Maritime pine (Pinus pinaster Aiton) grows in a range of different climates in the southwestern Mediterranean region and the existence of a variety of latitudinal ecotypes or provenances is well established. In this study, we have conducted a deep analysis of the transcriptome in needles from two P. pinaster provenances, Leiria (Portugal) and Tamrabta (Morocco), which were grown in northern Spain under the same conditions.', 'An oligonucleotide microarray (PINARRAY3) and RNA-Seq were used for whole-transcriptome analyses, and we found that 90.95% of the data were concordant between the two platforms. Furthermore, the two methods identified very similar percentages of differentially expressed genes with values of 5.5% for PINARRAY3 and 5.7% for RNA-Seq. In total, 6,023 transcripts were shared and 88 differentially expressed genes overlapped in the two platforms. Among the differentially expressed genes, all transport related genes except aquaporins were expressed at higher levels in Tamrabta than in Leiria. In contrast, genes involved in secondary metabolism were expressed at higher levels in Tamrabta, and photosynthesis-related genes were expressed more highly in Leiria. The genes involved in light sensing in plants were well represented in the differentially expressed groups of genes. In addition, increased levels of hormones such as abscisic acid, gibberellins, jasmonic and salicylic acid were observed in Leiria.",
            "output": [
                "Does transcriptome-wide analysis support environmental adaptations of two Pinus pinaster populations from contrasting habitats?"
            ]
        },
        {
            "id": "task847-a3b07530d58d4d0e862ed0d6cbcc9044",
            "input": "Precise long-term assessment of movement and physical function following Achilles tendon rupture is required for the development and evaluation of treatment, including different regimens of physical therapy.', 'To assess intermediate-term (<10 years by conventional thinking) objective measures of physical function following Achilles tendon rupture treated nonsurgically and to compare these with self-reported measures of physical function.', 'Cross-sectional study; Level of evidence, 3.', 'Two to 5 years after Achilles tendon rupture, 9 women and 43 men (mean age, 49.2 years; range, 26-68 years) were assessed by physical examination, performance of 1-legged jumps, and 3-dimensional gait analysis (including calculation of muscle work). Self-reported scores for foot function (Achilles tendon rupture score) and level of physical activity were collected. Twenty age- and sex-matched controls were assessed in the same manner.', 'Physical examination of patients with the knee extended revealed 11.1\u00b0 of dorsiflexion on the injured side and 9.2\u00b0 on the uninjured side (P = .020), indicating gastrocnemius muscle lengthening. The 1-legged jump distance was shorter on the injured side (89.5 vs 96.2 cm; P < .001). Gait analysis showed higher peak dorsiflexion (14.3\u00b0 vs 13.3\u00b0; P = .016) and lower concentric (positive) plantar flexor work (16.6 vs 19.9 J/kg; P = .001) in the ankle on the uninjured side. At the same time, eccentric (negative) dorsiflexor work was higher on the injured side (13.2 vs 11.9 J/kg; P = .010). Self-perceived foot function and physical activity were lower in patients than in healthy controls (mean Achilles tendon rupture score, 78.6 and 99.8, respectively).",
            "output": [
                "Does three-Dimensional Gait Analysis Following Achilles Tendon Rupture With Nonsurgical Treatment reveal Long-Term Deficiencies in Muscle Strength and Function?"
            ]
        },
        {
            "id": "task847-192db59e64b04d3e8d06eff2a3ad84d1",
            "input": "The effects of prenatal cigarette smoke (CS) exposure and hypoxemia on cardiorespiratory control have been investigated in full-term infants. However, few data are available in preterm infants, who form a particularly vulnerable population, with developmentally immature cardiorespiratory control.', 'To investigate the effects of prenatal CS exposure on the duration and recovery of breathing pauses and oxygen saturation levels under baseline and hypoxemic conditions in preterm infants.', \"The study was performed on 22 (12 born to smoking and 10 to nonsmoking mothers) spontaneously breathing preterm infants between 28 and 36 weeks' gestation. Cardiorespiratory variables were recorded under baseline normoxemic and hypoxemic conditions.\", 'Breathing pauses, pause indices, time to recovery, percent pause recovery, oxygen saturation (Sp(O2)), periods of wakefulness, and cardiorespiratory rates were compared between the two groups. Spontaneous recovery of breathing pauses (P = 0.03) and Sp(O(2)) levels (P = 0.017) were attenuated in CS-exposed infants as compared with the control group during the hypoxemic and posthypoxemic periods, respectively. The episodes of wakefulness during the hypoxemic challenge were similar between the two groups. Furthermore, CS-exposed infants showed a greater increase in heart rate (P < 0.001) during the hypoxemic challenge when compared with control infants.",
            "output": [
                "Does prenatal cigarette smoke exposure attenuate recovery from hypoxemic challenge in preterm infants?"
            ]
        },
        {
            "id": "task847-9e4126f6ca5e4b5bb5fe3bff5be92646",
            "input": "Several reports suggest that the rat Vcsa1 gene is down-regulated in models of erectile dysfunction. The Vcsa protein product sialorphin is an endogenous neutral endopeptidase inhibitor and its down-regulation could result in prolonged activation of G-protein activated signaling pathways by their peptide agonists. We investigated whether Vcsa1 down-regulation could result in an adaptive change in GPCR (G-protein coupled receptor) expression.', 'Gene expression in cultured rat corporeal smooth muscle cells following treatment with siRNA directed against Vcsa1 or the neutral endopeptidase gene was analyzed using microarray and quantitative reverse transcriptase-polymerase chain reaction. In rats Vcsa1 is one of the most down-regulated genes following bilateral transection of the cavernous nerves. In that animal model we also investigated whether Vcsa1 down-regulation was accompanied by similar changes in gene expression in corporeal smooth muscle cells in which Vcsa1 was knocked down in vitro.', 'Microarray analysis and quantitative reverse transcriptase-polymerase chain reaction demonstrated that corporeal smooth muscle cells treated in vitro with siRNA against Vcsa1 resulted in GPCR up-regulation as a functional group. In contrast, treatment of corporeal smooth muscle cells that lowered neutral endopeptidase activity resulted in decreased GPCR expression. These results suggest that the peptide product of Vcsa1, sialorphin, can effect GPCR expression by acting on neutral endopeptidase. In animals with bilaterally transected cavernous nerves the decreased Vcsa1 expression is accompanied by increased GPCR expression in cavernous tissue.",
            "output": [
                "Is transcription of G-protein coupled receptors in corporeal smooth muscle regulated by the endogenous neutral endopeptidase inhibitor sialorphin?"
            ]
        },
        {
            "id": "task847-604e6a51c36f4abfb65232b9f7fef2ec",
            "input": "To identify clinical predictors of malignancy in patients with intraoperative frozen-section diagnosis of follicular neoplasm of the thyroid.', 'We performed a retrospective cross-sectional study of 71 patients with intraoperative frozen-section diagnosis of follicular neoplasm who underwent thyroidectomy between January 1992 and December 2000. Age, sex, tumor size, and in-office ultrasonography characteristics of the lesions were assessed. These clinical factors were compared between cases that had benign definitive pathologic findings and those that were found to be carcinomas on permanent sections.', 'Nine (13%) of the 71 follicular neoplasms were found to be carcinomas after definitive pathologic evaluation. The incidence of malignancy was 13% (2/16) in men and 13% (7/55) in women (P>.5). Patients younger than 45 years had a 27% (8/30) incidence of malignancy compared with 2% (1/41) in patients 45 years or older (P<.01). Of tumors smaller than 4 cm, 7% (4/55) were ultimately diagnosed as carcinomas compared with 31% (5/16) of those 4 cm or larger (P = .05). When the in-office ultrasonography findings were interpreted as benign, only 7% (3/46) of cases were malignant compared with 40% (4/10) when the ultrasonography findings were suspicious (P = .02).",
            "output": [
                "Are age , tumor size , and in-office ultrasonography predictive parameters of malignancy in follicular neoplasms of the thyroid?"
            ]
        },
        {
            "id": "task847-4cea2c065fb74bf68beece145411b9f2",
            "input": "To investigate the effects of dexamethasone (DEX) on pigment epithelium-derived factor (PEDF) cDNA and secreted protein in human trabecular meshwork (TM).', 'Anterior segment organ cultures were perfused with 0.1 microM DEX (OD) and vehicle (OS). Primary human TM cells (HTM) were treated with DEX under similar conditions. PEDF mRNA and secreted PEDF protein were quantitated by RT-PCR and Western blot.', 'PEDF mRNA and secreted PEDF protein levels were significantly higher in DEX over vehicle-treated cultures. In contrast, DEX decreased the activity of a 92-kDa gelatinolytic zymogen in organ culture effluents.",
            "output": [
                "Does dexamethasone increase pigment epithelium-derived factor in perfused human eyes?"
            ]
        },
        {
            "id": "task847-c0a80c0b11b340809b784a93d7f92dc4",
            "input": "Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men.\", 'Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6x vs 1.5x, respectively at 10 muM), while fenofibrate did not induce changes in either.",
            "output": [
                "Are plasma PCSK9 levels significantly modified by statins and fibrates in humans?"
            ]
        },
        {
            "id": "task847-77b55b4302a34aa993c8fa612c694143",
            "input": "To investigate the effects of the expression of human kallikrein (HK) on basal level blood pressure and high-salt diet-induced hypertension.', 'We delivered the recombinant adeno-associated viral (rAAV)-mediated HK (rAAV- HK) gene and rAAV-LacZ (as the control) to normal, adult Sprague-Dawley rats. The animals were administered a normal diet in the first 4 weeks, followed by a high-salt diet. The expression of HK in the rats was assessed by ELISA and RT- PCR. Blood pressure and Na+ and K+ urinary excretion were monitored.', 'Under the normal diet, no obvious changes in blood pressure and Na+ and K+ urinary excretion were observed. When the high-salt diet was administered, systolic blood pressure in the control animals receiving rAAV-LacZ increased from 122.3+/-1.13 mmHg to a stable 142.4+/-1.77 mmHg 8 weeks after the high-salt diet. In contrast, there was no significant increase in the blood pressure in the rAAV-HKtreated group, in which the blood pressure remained at 121.9+/-1.73 mmHg. In the rAAV-HK-treated group, Na+ and K+ urinary excretion were higher compared to those of the control group. The morphological analysis showed that HK delivery remarkably protected against renal damage induced by a high-salt intake.",
            "output": [
                "Does recombinant adeno-associated virus-mediated human kallikrein gene therapy prevent high-salt diet-induced hypertension without effect on basal blood pressure?"
            ]
        },
        {
            "id": "task847-bea1c72facfe4f91a57a6bc3721a48aa",
            "input": "The angiopoietin-1 (Ang1)/Tie-2 signaling system not only plays a pivotal role in vessel growth, remodeling, and maturation, but also reduces apoptosis of endothelial cells, neurons, and cardiomyocytes. However, relatively little is known as to whether Ang1 has a protective effect on mesenchymal stem cells (MSC). The aim of the present study was to investigate the protective effect of Ang1/Tie-2 signaling on MSC against serum deprivation and hypoxia-induced apoptosis, and to determine the possible mechanisms.', 'Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling staining were used to assess the apoptosis of MSC. The expression of Tie-2, Akt, Bcl-2, Bax, and cleaved caspase-9 and -3 was detected by Western blot analysis.', 'This study showed that MSC expressed Tie-2 receptor, and Ang1 induced Tie-2 receptor phosphorylation. The protective effect of Ang1 on MSC was dose-dependent and peaked at 50 microg/L; however, the soluble Tie-2/Fc fusion protein, which acts as an inhibitor by sequestering Ang1, abrogated the anti-apoptotic effect. Ang1 induced Akt phosphorylation, increased the Bcl-2/Bax ratio, and decreased the activation of caspase-9 and -3. All these effects were attenuated by Tie-2/Fc and a phosphatidylinositol 3 kinase (PI3K) inhibitor, wortmannin.",
            "output": [
                "Does angiopoietin-1 protect mesenchymal stem cells against serum deprivation and hypoxia-induced apoptosis through the PI3K/Akt pathway?"
            ]
        },
        {
            "id": "task847-bc268fcc29714a60a621bb12188623cf",
            "input": "Ischemia-reperfusion injury (IRI) to the lower extremities causes both local damage and serious dysfunction to remote organs, including lungs and kidneys. However, effective therapies are not available. This study aims to determine if simvastatin reduced the severity of remote damage following IRI.', 'Rats were given simvastatin before hind limb IRI. Lung and kidney tissues were assessed for neutrophil infiltration using myeloperoxidase assays and basement membrane damage by quantitative immunohistochemical measurement of collagen IV. The effect of nitric oxide synthase (NOS) inhibition on remote damage after IRI and simvastatin was assessed using the NOS inhibitor, L-NIO.', 'Simvastatin (2 mg/kg) protected kidneys against IRI-induced neutrophil infiltration. Simvastatin also inhibited the IRI-induced activation of MMP-9 in the lungs. However, paradoxically, simvastatin exacerbated IRI-induced neutrophil infiltration into the lungs. IRI induced collagen IV degradation in the lungs but not in the kidneys. The degree of collagen breakdown in the lungs was significantly ameliorated by 2 mg/kg simvastatin. NOS inhibition markedly protected both the lungs and the kidneys against IRI-induced neutrophil infiltration but did not alter collagen IV degradation. Administration of simvastatin to L-Nio-treated animals enhanced the degree of protection against IRI-induced neutrophil infiltration in the kidneys but not in the lungs.",
            "output": [
                "Does simvastatin plus nitric oxide synthase inhibition modulate remote organ damage following skeletal muscle ischemia-reperfusion injury?"
            ]
        },
        {
            "id": "task847-78b126223b4549129274ca60e05f42ee",
            "input": "In essential hypertensive patients, blunted renal plasma flow responsiveness to angiotensin II suggests a pathologic increase in angiotensin II in the kidneys. This blunting has been associated with the angiotensinogen 235TT genotype. As several measures of renal function decline with age, we sought to determine the interaction of age and genotype on this intermediate phenotype.', 'Three hundred fifteen participants had renal plasma flow response to subpressor doses of angiotensin II (3 ng/kg/min) measured by para-aminohippuric acid clearance in high-sodium balance. Individuals were divided by median age into young (<45 years) and older (> or =45 years) sets. A subset of participants was also studied after administration of captopril.', 'Age, baseline renal plasma flow, BMI and angiotensinogen 235 genotype independently predicted renal plasma flow responsiveness to angiotensin II. Renal plasma flow responses were lower in older individuals than younger (P = 0.03, hypertensive patients; P = 0.004, normotensive individuals). Both hypertensive patients and normotensive individuals carrying either angiotensinogen 235MM or MT genotypes showed this inverse association (P = 0.005, hypertensive patients; P = 0.05, normotensive individuals). However, among angiotensinogen 235TT homozygotes the pattern differed: normotensive individuals had a fall in renal vascular responsiveness with age (P = 0.01) but hypertensive patients did not (P = 0.72). Young hypertensive patients already showed blunted responses. Of all genotype subsets, only angiotensinogen 235TT hypertensive patients showed enhancement (P = 0.03) of the renal vascular responsiveness to angiotensin II after captopril.",
            "output": [
                "Does angiotensinogen genotype predict abnormal renal hemodynamics in young hypertensive patients?"
            ]
        },
        {
            "id": "task847-f5b6833cdf024607aa0d2b286a78c965",
            "input": "Sugar consumption affects insulin release and, in hypertension, may stimulate cardiac signaling mechanisms that accelerate left ventricular hypertrophy and the development of heart failure. We investigated the effects of high-fructose or sucrose diets on ventricular function and mortality in hypertensive Dahl salt-sensitive rats.', 'Rats were fed chows that were either high starch (70% starch, 10% fat by energy), high fat (20% carbohydrates, 60% fat), high fructose (61% fructose, 9% starch, 10% fat), or high sucrose (61% sucrose, 9% starch, 10% fat). Hypertension was induced by adding 6% salt to the chow (n = 8-11/group).', 'After 8 weeks of treatment, systolic blood pressure and left ventricular mass were similarly increased in all rats that were fed high-salt diets. Hypertension caused a switch in mRNA myosin heavy chain isoform from alpha to beta, and this effect was greater in the high-salt sucrose and fructose groups than in starch and fat groups. The cardiac mRNA for atrial natriuretic factor was also increased in all high-salt groups compared to respective controls, with the increase being significantly greater in the hypertensive sucrose fed group. Mortality was greater in the sucrose group (44%) compared to all the other hypertensive groups (12-18%), as was cardiomyocyte apoptosis. Left ventricular ejection fraction was lower in the high-salt sucrose group, which was due to an increase in end-systolic volume, and not increased end-diastolic volume.",
            "output": [
                "Do high-sugar diets increase cardiac dysfunction and mortality in hypertension compared to low-carbohydrate or high-starch diets?"
            ]
        },
        {
            "id": "task847-aded3d9f7b7e46c392b4f02211f81b52",
            "input": "To evaluate amiodarone prophylaxis in diabetics and non-diabetics. Further to clarify whether the risk of developing atrial fibrillation is higher for diabetics than non-diabetic patients, and to evaluate whether the diabetic status has any influence on the length of in-hospital stay.', 'Subgroup analysis within a randomized, controlled, double-blinded trial.', 'At 30 days of follow-up atrial fibrillation was equally frequent among diabetics (22%) and non-diabetics (17%) (p =0.41). The length of in-hospital stay for diabetics was prolonged with 25% (9%; 45%). The prophylactic amiodarone was found equally efficient in diabetics and non-diabetics, as the relative risk ratios were 1.2 (0.4-5.4) and 2.0 (0.3-12.5), respectively.",
            "output": [
                "Does amiodarone protect diabetics and non-diabetics undergoing coronary artery bypass grafting equally?"
            ]
        },
        {
            "id": "task847-c5befe66069f4fa78f8d1df9cac6946e",
            "input": "Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans.', 'We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction.', 'Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables-including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine-6-8 hr after both exposures.', 'Particulate concentrations (mean +/- SE) in the exposure chamber (190+/-37 microg/m(3)) were higher than ambient levels (31+/-8 microg/m(3)) and levels in filtered air (0.5+/-0.4 microg/m(3); p<0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9+/-8.5 vs. 4.9+/-1.2 pg/mL, p<0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p<0.001 for all), CAPs exposure had no effect on vascular function in either group.",
            "output": [
                "Does exposure to concentrated ambient particles affect vascular function in patients with coronary heart disease?"
            ]
        },
        {
            "id": "task847-14d7bc6c6bed4705b2526365536536b1",
            "input": "The aim of this study was to investigate the ability of serotonin to increase contractions in human myometrium.', 'Isometric tension measurements were used to determine the effect of increasing doses of serotonin on strips of human myometrium obtained at the time of cesarean section.', 'Serotonin had little or no effect on the spontaneous activity of myometrium strips in control conditions. In tissue where this activity had been reduced by either forskolin or diazoxide, serotonin caused a dose-dependent increase in contractions and produced up to a 3-fold increase in contractions over basal activity.",
            "output": [
                "Is stimulation of contractions in human myometrium by serotonin unmasked by smooth muscle relaxants?"
            ]
        },
        {
            "id": "task847-28712a7ff2a04e5cba61475e568c6c59",
            "input": "Chromosome 22q11.2 deletion syndrome is one of the most common genetic causes of cognitive impairment and developmental disability yet little is known about the neural bases of those challenges. Here we expand upon our previous neurocognitive studies by specifically investigating the hypothesis that changes in neural connectivity relate to cognitive impairment in children with the disorder.', 'Whole brain analyses of multiple measures computed from diffusion tensor image data acquired from the brains of children with the disorder and typically developing controls. We also correlated diffusion tensor data with performance on a visuospatial cognitive task that taps spatial attention.', 'Analyses revealed four common clusters, in the parietal and frontal lobes, that showed complementary patterns of connectivity in children with the deletion and typical controls. We interpreted these results as indicating differences in connective complexity to adjoining cortical regions that are critical to the cognitive functions in which affected children show impairments. Strong, and similarly opposing patterns of correlations between diffusion values in those clusters and spatial attention performance measures considerably strengthened that interpretation.",
            "output": [
                "Are atypical cortical connectivity and visuospatial cognitive impairments related in children with chromosome 22q11.2 deletion syndrome?"
            ]
        },
        {
            "id": "task847-a0f1d1a6a86e459989ee16f0127c1fd5",
            "input": "This exploratory study assessed how 8-13-year-old children categorised and labelled fruit and vegetables (FaV), and how these were influenced by child characteristics, to specify second-level categories in a hierarchical food search system for a computerised 24 h dietary recall (hdr).', 'Two sets of food cards, sixty-seven for fruit (F) and sixty-four for vegetables (V), with pictures and names of FaV from ten professionally defined food categories were sorted, separately, by each child into piles of similar foods. Demographic data, BMI and 6-n-propylthiouracil (PROP) taster status were obtained.', \"Participants attended the Children's Nutrition Research Center in the summer of 2006.\", 'In all, 152 8-13-year-old children, predominantly English-speaking, of whom sixteen were predominantly Spanish-speaking.', \"Children created an average of 8.5 (5.3) piles with 7.9 (11.4) cards per pile for the F, and an average of 10.1 (4.8) piles with 6.2 (7.9) cards per pile for the V. No substantial differences in Robinson clustering were detected across subcategories for each of the demographic characteristics, BMI or PROP sensitivity. Children provided clusters names that were mostly 'Taxonomic - Professional' labels, such as salads, berries, peppers, for both F (51.8 %) and V (52.1 %).",
            "output": [
                "Are fruit and vegetables similarly categorised by 8-13-year-old children?"
            ]
        },
        {
            "id": "task847-75baa1ba850940e1a2e7b4107b2716db",
            "input": "Guidelines recommend upper endoscopic screening of cirrhotic patients for gastroesophageal varices. Cirrhosis is not always distinguishable from chronic hepatitis.', 'To identify low-risk patients who can be spared upper endoscopy irrespective of a diagnosis of cirrhosis.', 'We evaluated 13 nonendoscopic variables as predictors of esophagogastric varices in 254 patients with hepatitis B or hepatitis C-related chronic liver disease who underwent upper endoscopy.', 'Any size varices occurred in 30.3% (77/254), and large varices in 12.2% of patients (31/254). Age >50 years [odds ratio (OR): 11.29; 95% confidence interval (CI): 2.33-54.67], platelet count <150,000/mmc (OR: 4.40; 95% CI: 1.85-10.45), albumin <3.6 g/dL (OR: 2.99; 95% CI: 1.31-6.79), and aspartate aminotransferase/alanine aminotransferase ratio >1 (OR: 2.83; 95% CI: 1.26-6.34) independently predicted varices by logistic regression. Using a score based on age >50 years, platelets <150,000/mmc, and aspartate aminotransferase/alanine aminotransferase ratio >1 (1 point/predictor), only 3.2% of patients with a score <2 had varices, all small.",
            "output": [
                "Does a simple noninvasive score predict gastroesophageal varices in patients with chronic viral hepatitis?"
            ]
        },
        {
            "id": "task847-f3c80fad0ab34679b49ce4797786e1fb",
            "input": "Epidemiological prospective data on cardiovascular (CV) events in elderly subjects from Mediterranean populations are lacking. We aimed to investigate 15-year incidence of CV events and to evaluate the association with CV risk factors in an elderly Mediterranean population.', 'The population of a small Sicilian village were enrolled, visited and a blood sample was drawn at baseline. CV events were recorded in the 15 years of follow-up. From 1351 subjects (75% of the resident population); 315 were in the age range 65-85 years; 266 subjects free from CV disease were analysed. Seventy-seven CV events were recorded in 73 out of 266 subjects, with a 19.7% rate (in 10 years). Hypertension (HTN) (hazards ratio=2.1) and diabetes mellitus (DM) (hazards ratio=1.8) were independently associated with CV events. Subjects with both DM and HTN showed a lower survival free of CV events compared to those with DM or HTN.",
            "output": [
                "Are hypertension and diabetes mellitus associated with cardiovascular events in the elderly without cardiovascular disease . Results of a 15-year follow-up in a Mediterranean population?"
            ]
        },
        {
            "id": "task847-27d0a6e4019d4ff9a0e33f59ecc5fcc5",
            "input": "Mice deficient in apolipoprotein E (apoE(-/-)) develop atherosclerosis. The possible linkage between expression of adhesion molecules/cofactors and atherosclerosis was probed at the level of mRNA and protein expression. The hypothesis of a linkage between changes of adhesion molecules/cofactors and atherosclerosis was tested further by suppression of aortic lesion formation in apoE(-/-) mice by expression of very low levels of transgenic apolipoprotein E.', 'We show that at 8.5 months of age, the apoE(-/-) mice display elevated expression of mRNA for LFA-1, MAC-1, VCAM-1, ICAM-1, and for CD44, as well as MCP-1, cathepsin B, and COX-2 (but not that for eNOS) in atherosclerotic aortic arches. At earlier age, (10-13 week old) apoE(-/-) mice already display elevated expression of mRNA of CD44, LFA-1, MAC-1, VCAM-1, ICAM-1, cathepsin, and of COX-2 in lesioned aortic arches. Expressing very low levels of transgenic apolipoprotein E suppresses both aortic lesions and the expression of mRNA of LFA-1, VCAM-1, MCP-1, cathepsin B, and of ICAM-1 in ApoE(-/-) mice. We tested at the level of protein, the observations obtained for mRNA expression. CD11a (a component of LFA-1), VCAM-1 and cathepsin B expression was found to be elevated in apoE(-/-) aortas at 8-9 months; low level expression of transgenic apolipoprotein E rectifies these changes.",
            "output": [
                "Is altered gene expression in early atherosclerosis blocked by low level apolipoprotein E?"
            ]
        },
        {
            "id": "task847-40a2427c42174d4eb8d2924a475ca4db",
            "input": "Overexpression of the human c-MYC (MYC) oncogene is one of the most frequently implicated events in the pathogenesis of hepatocellular carcinoma (HCC). Previously, we have shown in a conditional transgenic mouse model that MYC overexpression is restrained from inducing mitotic cellular division and tumorigenesis in the adult liver; whereas, in marked contrast, MYC induces robust proliferation associated with the very rapid onset of tumorigenesis in embryonic and neonatal mice.', 'Here, we show that non-genotoxic hepatotoxins induce changes in the liver cellular context associated with increased cellular proliferation and enhanced tumorigenesis. Both 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl(4)) cooperate with MYC to greatly accelerate the onset of liver cancer in an adult host to less than 7 days versus a mean latency of onset of over 35 weeks for MYC alone. These hepatotoxin-enhanced liver tumors grossly and histologically resemble embryonic and neonatal liver tumors. Importantly, we found that MYC overexpression is only capable of inducing expression of the mitotic Cyclin B1 in embryonic/neonatal hosts or adult hosts that were treated with either carcinogen.",
            "output": [
                "Do hepatotoxin-induced changes in the adult murine liver promote MYC-induced tumorigenesis?"
            ]
        },
        {
            "id": "task847-d6539b9d9b4e475cab9fd131ede055b6",
            "input": "To investigate the prognostic value of the pre-treatment haemoglobin level in patients with advanced squamous cell head and neck cancer treated with induction polychemotherapy.', 'Seventy-two patients with advanced squamous cell head and neck cancer received primary combination chemotherapy consisting of docetaxel 75 mg/m(2) on day 1, cisplatin 100 mg/m(2) on day 1, and 5-fluorouracil (5-FU) 1000 mg/m(2)/day on days 1-4 (total dose 4000 mg/m(2)), repeated on days 1, 22 and 43 followed by chemoradiation. The data collected included pre-treatment haemoglobin, response to treatment, disease-free and overall survival.', 'The pre-treatment haemoglobin level was found to be a significant predictor of response to induction chemotherapy (P = 0.01) and an independent predictor of overall survival [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.58-1.03, P = 0.0001] and disease free survival (HR 2.09, 95% CI 1.41-3.09, P = 0.0001). Furthermore N-stage was found to be a significant prognostic factor of overall survival (HR 9.24, 95% CI 6.90-21.34, P = 0.005). The Eastern Cooperative Oncology Group performance status scale was also found to be significant for disease free survival (HR 7.66, 95% CI 2.61-22.46, P = 0.003).",
            "output": [
                "Does pre-treatment haemoglobin level predict response and survival after TPF induction polychemotherapy in advanced head and neck cancer patients?"
            ]
        },
        {
            "id": "task847-612fff65c554424d999b9d0e8b1e02e3",
            "input": "Type I interferons (IFN) include multiple IFN-alpha subtypes which exhibit considerable amino acid identity and activate the same cell-surface receptor. The promoter regions of the IFN-alpha genes, however, have different transcription factor binding sites, implying differential transcriptional activation. Evolutionary conservation of multiple subtypes may have resulted from external pressures associated with the crucial nature of an IFN response, namely that different viruses that are tropic for different target tissues determine the nature and extent of an IFN response, specifically the IFN-alpha subtype profile.', 'Studies were undertaken to examine inducible IFN gene expression profiles in response to infection with single-stranded RNA viruses: Sendai virus (SeV), murine hepatitis virus (MHV-1) and coxsackie virus B3 (CVB3).', 'In vitro, distinct signature profiles of SeV and MHV-1-inducible gene expression for IFN-alpha2, IFN-alpha4 and IFN-alpha5 subtypes in L2 and L929 mouse fibroblast cells, in relation to the extent and kinetics of their induction, were identified. In vivo, whereas A/J mice are highly permissive for both MHV-1 and CVB3 infections and mount a poor IFN response, C57B1/6 mice are relatively resistant to both virus infections and mount a vigorous IFN response.",
            "output": [
                "Are distinct signature type I interferon responses determined by the infecting virus and the target cell?"
            ]
        },
        {
            "id": "task847-69f70b4a6340440dbb03cb0e9de3c517",
            "input": "Adefovir dipivoxil (ADV) has demonstrated activity against wild-type and lamivudine-resistant hepatitis B virus (HBV). After 1 year of therapy, a median 3.5-4.0 log10 decrease in viral load is observed. Our aim was to characterize the different profiles of response to ADV in relation to the in vitro susceptibility of viral strains to ADV.', 'In an international Phase III randomized, placebo-controlled study of ADV in patients positive for hepatitis B virus e antigen (HBeAg), different profiles of virological response to ADV 10 mg/day were identified at week 48. The top 25% patients (quartile 1, Q1) showed > 4.91 log10 reduction in serum HBV DNA at week 48, in Q2 patients demonstrated a 3.52 to 4.90 log10 reduction of viral load, whereas in Q3 a 2.22 to 3.51 log10 reduction in viral load was observed. The bottom 25% of patients (Q4) showed < 2.22 log10 reduction in HBV DNA levels. The influence of baseline characteristics and drug compliance on response was investigated. The replication capacity and drug susceptibility of HBV genomes of selected clinical isolates that were considered representative of the treatment response quartiles were analysed using a phenotypic assay.', 'The lowest quartile of response (Q4) appears to have worse compliance. Higher alanine aminotransferase levels at baseline are associated with improved response. Phenotypic analysis of viral strains in vitro in Huh7 and HepG2 cells showed that HBV genomes remained susceptible to ADV, regardless of treatment response observed in patients.",
            "output": [
                "Is suboptimal response to adefovir dipivoxil therapy for chronic hepatitis B in nucleoside-naive patients due to pre-existing drug-resistant mutants?"
            ]
        },
        {
            "id": "task847-5f44a768b163477f800cac61382cf59d",
            "input": "Several biomarkers indicating poor prognosis have been reassessed in patients receiving rituximab combination chemotherapy for diffuse large B-cell lymphoma (DLBCL). However, few studies have investigated outcome in relation to a combination of these biomarkers. In addition, no large-scale studies have reassessed the outcome of patients with CD5-positive DLBCL treated with rituximab.', 'We conducted a retrospective study and investigated the predictive value of three biomarkers -- BCL2, germinal center (GC) phenotype and CD5 -- in 121 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone.', 'CD5-positive patients showed significantly poorer event-free survival (EFS) and overall survival (OS) than CD5-negative patients (2-year EFS, 18% versus 73%, P < 0.001; 2-year OS, 45% versus 91%, P = 0.001). However, no significant difference in outcome according to BCL2 or GC phenotype was observed. Multivariate analysis revealed that CD5 expression was a significant prognostic factor for EFS [hazard ratio 14.2, 95% confidence interval (CI) 4.7-43.2] and OS (hazard ratio 20.3, 95% CI 3.6-114.4).",
            "output": [
                "Is cD5 expression potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy?"
            ]
        },
        {
            "id": "task847-6b03bd16457c47e5a2782fd13d3dbe6d",
            "input": "To compare two solutions for fluid resuscitation in post-coronary artery bypass grafting (CABG) surgery patients: Ringer's lactate (RL) versus a new solution containing half-molar sodium-lactate (HL).\", 'Prospective randomized open label study.', 'The first 12 h post-CABG surgery in an intensive care unit (ICU).', 'There were 230 patients enrolled in the study: 208 were analyzed, with 109 from the HL group and 99 from the RL group.', 'Patients received over the first 12 h post-CABG 10 ml kg BW(-1) HL solution in the HL group versus 30 ml kg BW(-1) of RL solution in the RL group.', 'Hemodynamic status, body fluid balance and inotrope utilization were compared in the two groups. Post-operative cardiac index increase was significantly higher in HL than in RL (P = 0.02), while mean arterial pressure and other hemodynamic parameters were comparable together with urinary output, indicating similar tissue perfusion in both the groups despite a much lower fluid infusion in the HL group. Therefore, a significant negative fluid balance was achieved in the HL but not in the RL group (-790 +/- 71 vs. +43 +/- 115 mL 12 h(-1), P < 0.0001 for HL and RL, respectively). None of the enrolled patients exhibited side effects related to the treatment.",
            "output": [
                "Does half-molar sodium-lactate solution have a beneficial effect in patients after coronary artery bypass grafting?"
            ]
        },
        {
            "id": "task847-e2dec6a16aad4969952fa9562117ead0",
            "input": "Low resting energy expenditure (REE) and respiratory quotient (RQ) have been shown in adults to predispose to obesity and diabetes mellitus.', 'To correlate REE and RQ in 73 obese children and young adults (body mass index [BMI] 37 +/- 10 kg/m2) with measures of insulin secretion and resistance (IR) indices, percent carbohydrate and fat oxidation, and prolactin and leptin levels.', 'During a 3-day admission, REE and RQ were determined by indirect calorimetry. Blood chemistries and oral glucose tolerance test (OGTT) were obtained, and intravenous glucose tolerance test (IVGTT) modified by tolbutamide was conducted after an overnight fast, permitting calculation of acute insulin response (AIR), insulin resistance (SiIVGTT), and disposition index (DI).', 'Patients fell into two groups according to their SiIVGTT: those with normal insulin sensitivity (NIS) and those with insulin resistance (IR). IR patients were subdivided on the basis of DI (cut-off value 0.13 min(-1)) into compensated (CIR) or decompensated (DIR) groups. CIR patients had higher RQ, REE corrected by BMI, AIR, and carbohydrate oxidation and lower fat oxidation than NIS and DIR patients. REE correlated positively with BMI, leptin, and AIR, and negatively with SiIVGTT.",
            "output": [
                "Does resting energy expenditure in insulin resistance fall with decompensation of insulin secretion in obese children?"
            ]
        },
        {
            "id": "task847-b5100ced7fad4a0e911d8164ee4e5a7f",
            "input": "Inflammatory stimuli profoundly increase the vulnerability of the vessel wall to atherogenesis. The endothelial glycocalyx, a layer of glycosaminoglycans and proteoglycans covering the luminal side of the vasculature, has recently emerged as an orchestrator of vascular homeostasis. In the present study, we investigated whether endotoxin-induced inflammatory reactions lead to a decrease of endothelial glycocalyx thickness in humans and whether tumor necrosis factor-alpha (TNFalpha) plays a role in this process.', 'Healthy male volunteers received low-dose endotoxin (1ng/kg) intravenously, with (n=8) or without (n=13) pre-treatment with the soluble TNFalpha receptor etanercept. Endothelial glycocalyx thickness and related parameters were determined after endotoxin challenge.', 'Endotoxin resulted in a profound reduction in microvascular glycocalyx thickness (from 0.60+/-0.1 to 0.30+/-0.1microm, p<0.01). Concomitantly, plasma levels of the principal glycocalyx constituent hyaluronan (62+/-18 to 85+/-24ng/mL, p<0.05), monocyte activation and coagulation activation increased (F1+2; 0.3+/-0.1 to 2.8+/-1.5nmol/L, p<0.05 and d-dimer; from 0.2+/-0.1 to 0.4+/-0.1mg/L, p<0.05 compared to baseline). Inhibition of TNFalpha by etanercept attenuated loss of microvascular glycocalyx thickness (0.54+/-0.1 to 0.35+/-0.1mum, p<0.05). Changes in hyaluronan (58+/-13 to 46+/-10ng/mL, p<0.05) and coagulation activation were also attenuated (F1+2; 0.3+/-0.1 to 2.1+/-0.9nmol/L and d-dimer; from 0.2+/-0.1 to 0.3+/-0.1mg/L, p<0.05 compared to baseline).",
            "output": [
                "Does tumor necrosis factor-alpha inhibition protect against endotoxin-induced endothelial glycocalyx perturbation?"
            ]
        },
        {
            "id": "task847-d4a9d9ed92bc47909ab80f5f3f3fd327",
            "input": "To evaluate the effect of the fibrin sealant, Evicel, on the neuroregulatory control of penile erections in an experimental rat model.', 'Two groups of rats were used: sham-operated rats with exposure of the bilateral cavernous nerves (CNs) and application of saline vehicle (500 microL), and rats treated with direct application of Evicel (500 microL) bilaterally to the CNs. At 14 and 45 days after application of Evicel to the CNs, the CNs were stimulated to measure the in vivo erectile responses. Additionally, we evaluated the neuronal nitric oxide synthase immunoreactivity in the dorsal CNs of the penis and changes in the smooth muscle and collagen deposition in the penis using a trichrome stain.', 'Evicel application to the CNs did not have any detrimental effect on the neurogenic erectile responses in vivo at 14 or 45 days after application. The neuronal nitric oxide synthase expression in the dorsal CNs of the penis was unchanged after Evicel application at all points studied, and we saw no change in the histomorphometric analysis findings of smooth muscle and collagen deposition in the penis.",
            "output": [
                "Does application of Evicel to cavernous nerves of the rat influence erectile function in vivo?"
            ]
        },
        {
            "id": "task847-74d1d9e181bb43a78ee56c969e18f2f0",
            "input": "Pulmonary dysfunction presumably linked to an inflammatory response is frequent after cardiac operations using cardiopulmonary bypass (CPB) and pulmonary hypoperfusion. We previously demonstrated that active perfusion of the lungs during CPB reduces ischemic lung injury. We now hypothesized that avoiding ischemia of the lungs during CPB by active pulmonary perfusion would decrease pulmonary inflammatory response.', 'Pigs were randomized to a control group with CPB for 120 minutes, followed by 120 minutes of postbypass reperfusion, or to the study groups where animals underwent active pulmonary perfusion with pulsatile or nonpulsatile perfusion during CPB (n = 7 in each group). Activation of transcription factor activity (nuclear factor [NF]-kappaB and activating protein [AP]-1) was determined by electrophoretic mobility shift assay. Levels of proinflammatory protein expression (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha) were quantified by enzyme-linked immunoabsorbent assay. Caspase-3 activity was measured using a fluorogenic assay.', 'The activation of transcription factor AP-1 and NF-kappaB was reduced in the pulsatile pulmonary perfusion group. The caspase-3 activity and the expression of IL-1, IL-6, and TNF-alpha revealed a significant decrease in the pulsatile and nonpulsatile pulmonary perfusion groups. Animals of the pulsatile pulmonary perfusion group showed significantly reduced IL-6 expression and caspase-3 activity compared with the nonpulsatile pulmonary perfusion group.",
            "output": [
                "Does pulsatile pulmonary perfusion during cardiopulmonary bypass reduce the pulmonary inflammatory response?"
            ]
        },
        {
            "id": "task847-34a95737233a41e1bd7dab1276d30d16",
            "input": "Calcific aortic stenosis may be an inflammatory disease with active bone formation in the valve leaflets rather than a disease of passive calcium deposition. Epidemiologic data demonstrating correlation of poor dental hygiene to atherosclerotic pathologies suggests that circulating bacterial products could be involved in the pathogenesis of aortic valve stenosis. We hypothesized that lipopolysaccharide (LPS) stimulation of human aortic valve interstitial cells (HAVICs) would induce inflammatory and osteogenic gene expression.', 'The HAVICs were isolated from normal aortic valves obtained from explanted hearts during transplantation (n = 5) and grown in culture. Cells underwent 4 and 24 hours of LPS stimulation (LPS, 200 ng/mL) or beta-glycerol phosphate treatment (BGP) (osteogenic media as positive control). Media was removed for interleukin (IL)-6 and IL-8 immunoassay. Ribonucleic acid was extracted for microarray analysis. Statistics were by analysis of variance with post-hoc analysis (p < 0.05).', 'The LPS stimulation induced the gene expression of proinflammatory cytokines, chemokines, and adhesion molecules. Protein level confirmation by immunoassay demonstrated 3.4-fold (+/- 0.35, p < 0.01) and 9.5-fold (+/- 1.5 p < 0.01) increase over control of IL-6 and IL-8, respectively. The LPS and BGP both induced critical mediators of osteogenesis including bone morphogenetic protein 2 and platelet-derived growth factor alpha.",
            "output": [
                "Does lipopolysaccharide stimulation of human aortic valve interstitial cells activate inflammation and osteogenesis?"
            ]
        },
        {
            "id": "task847-defdea91495f415b8a9d629f59e2bd68",
            "input": "In rats, oral oleoyl-estrone (OE) decreases food intake and body lipid content. The aim of this study was to determine whether OE treatment affects the energy metabolism of pregnant rats and eventually, of their pups; i.e. changes in normal growth patterns and the onset of obesity after weaning.', 'Pregnant Wistar rats were treated with daily intragastric gavages of OE in 0.2 ml sunflower oil from days 11 to 21 of pregnancy (i.e. 10 nmol oleoyl-estrone/g/day). Control animals received only the vehicle. Plasma and hormone metabolites were determined together with variations in cellularity of adipose tissue.', \"Treatment decreased food intake and lowered weight gain during late pregnancy, mainly because of reduced adipose tissue accumulation in different sites. OE-treated pregnant rats' metabolic pattern after delivery was similar to that of controls. Neonates from OE-treated rats weighed the same as those from controls. They also maintained the same growth rate up to weaning, but pups from OE-treated rats slowed their growth rate afterwards, despite only limited differences in metabolite concentrations.",
            "output": [
                "Does treatment of pregnant rats with oleoyl-estrone slow down pup fat deposition after weaning?"
            ]
        },
        {
            "id": "task847-9200ba0c32d54d7eaf782d6744e559a3",
            "input": "Fatty acid synthase has been shown to be over expressed in a wide range of cancers and it has emerged as a therapeutic target. We examined whether fatty acid synthase could be a novel therapeutic target for renal cell carcinoma using the pharmacological fatty acid synthase inhibitor C75 (Cayman Chemical, Ann Arbor, Michigan).', 'The effects of C75 on cell viability and proliferation in human renal cancer 769P (ATCC(R)), Caki-1 and KU20-01 cells were examined by MTS assay and cell counts. Cell cycle distribution was analyzed by flow cytometry and cell invasiveness was assessed by wound healing and Matrigel(trade mark) invasion assays. Fatty acid synthase expression and the effects of C75 on intracellular signaling pathways were analyzed by Western blotting. The antitumor efficacy of C75 was examined using Caki-1 cell xenografts.', 'All renal cancer cell lines expressed detectable fatty acid synthase. C75 (10 mug/ml) significantly inhibited cell viability and growth by arresting the cell cycle at the G2/M phase and inducing apoptosis (p <0.01). The covered area in the wound and the number of cells invading through a Matrigel chamber were significantly smaller for cells treated with C75 than they were for control cells treated with vehicle (p <0.001). C75 suppressed Her2 and epidermal growth factor receptor expression as well as STAT3 phosphorylation, while increasing p53 and p21(Waf1/Cip1) expression. Intraperitoneal administration of C75 at doses of 20 mg/kg per week for 28 days significantly reduced the tumor volume of Caki-1 xenografts (p <0.05).",
            "output": [
                "Does pharmacological inhibitor of fatty acid synthase suppress growth and invasiveness of renal cancer cells?"
            ]
        },
        {
            "id": "task847-0b6ebe5dc8ec484da67784ae2dc457e2",
            "input": "The proteasome is a major cellular proteinase. Its activity is modulated by cellular oxidants. Hepatitis C core protein and ethanol exposure both cause enhanced oxidant generation. The aim was to investigate whether core protein, by its ability to generate oxidants, alters proteasome activity and whether these alterations are further affected by ethanol exposure.', 'These interactions were examined in Huh-7 cell lines that expressed inducible HCV core protein and/or constitutive cytochrome P450 2E1 (CYP2E1) and as purified components in a cell-free system. Chymotrypsin-like proteasome activity was measured fluorometrically.', 'Proteasome activity in core-positive 191-20 cells was 20% higher than that in core-negative cells and was enhanced 3-fold in CYP2E1-expressing L14 cells. Exposure of core-positive cells to glutathione ethyl ester, catalase, or the CYP2E1 inhibitor diallyl sulfide partially reversed the elevation of proteasome activity in core-positive cells, whereas ethanol exposure suppressed proteasome activity. The results indicate that proteasome activity was up-regulated by low levels of core-induced oxidative stress but down-regulated by high levels of ethanol-elicited stress. These findings were partially mimicked in a cell-free system. Addition of core protein enhanced the peptidase activity of purified 20S proteasome containing the proteasome activator PA28 and was further potentiated by addition of liver mitochondrial and/or microsome fractions. However, proteasome activation was significantly attenuated when fractions were obtained from ethanol-fed animals.",
            "output": [
                "Is proteasome activation by hepatitis C core protein reversed by ethanol-induced oxidative stress?"
            ]
        },
        {
            "id": "task847-019ee55f27bb4a689e10b2c21f8c762f",
            "input": "Although the cell of origin for pancreatic cancer remains unknown, prior studies have suggested that pancreatic neoplasia may be initiated in progenitor-like cells. To examine the effects of oncogene activation within the pancreatic progenitor pool, we devised a system for real-time visualization of both normal and oncogenic KRAS-expressing pancreatic progenitor cells in living zebrafish embryos.', 'By using BAC transgenes under the regulation of ptf1a regulatory elements, we expressed either extended green fluorescent protein (eGFP) alone or eGFP fused to oncogenic KRAS in developing zebrafish pancreas.', 'After their initial specification, normal eGFP-labeled pancreatic progenitor cells were observed to actively migrate away from the forming endodermal gut tube, and subsequently underwent characteristic exocrine differentiation. In contrast, pancreatic progenitor cells expressing oncogenic KRAS underwent normal specification and migration, but failed to differentiate. This block in differentiation resulted in the abnormal persistence of an undifferentiated progenitor pool, and was associated with the subsequent formation of invasive pancreatic cancer. These tumors showed several features in common with the human disease, including evidence of abnormal Hedgehog pathway activation.",
            "output": [
                "Does oncogenic KRAS induce progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas?"
            ]
        },
        {
            "id": "task847-aa7c2ec1355d4c7b9d68d4b14308e32f",
            "input": "The G-protein-coupled receptor GPR40 is expressed in pancreatic beta-cells and is activated by long-chain fatty acids. Gene deletion studies have shown that GPR40 mediates, at least in part, fatty acid-amplification of glucose-induced insulin secretion (GSIS) but is not implicated in GSIS itself. However, the role of GPR40 in the long-term effects of fatty acids on insulin secretion remains controversial. This study aimed to test the hypothesis that GPR40 plays a role in insulin secretion after high-fat feeding. RESEARCH DESIGN AND METHOD GPR40 knockout (KO) mice on a C57BL/6 background and their wild-type (WT) littermates were fed a high-fat diet (HFD) for 11 weeks. Glucose tolerance, insulin tolerance, and insulin secretion in response to glucose and Intralipid were assessed during the course of the diet period.', 'GPR40 KO mice had fasting hyperglycemia. They became as obese, glucose intolerant, and insulin resistant as their WT littermates given HFD and developed a similar degree of liver steatosis. Their fasting blood glucose levels increased earlier than those of control mice during the course of the HFD. The remarkable increase in insulin secretory responses to intravenous glucose and Intralipid seen in WT mice after HFD was of much lower magnitude in GPR40 KO mice.",
            "output": [
                "Does the fatty acid receptor GPR40 play a role in insulin secretion in vivo after high-fat feeding?"
            ]
        },
        {
            "id": "task847-abee284082dc43f2aa8691014994c58b",
            "input": "To propose a methodology for characterizing proficiency in sputum smear microscopy for acid-fast bacilli (AFB) in the diagnosis of tuberculosis and to determine the number of microscopies necessary to establish this proficiency, as well as the quality of the transcription of results, the causes of the discrepancies in the readings (rater or microscope used), and the criterion for classification of microscopy results that poses the most difficulty in characterizing proficiency.', 'Four hundred sputum smear microscopies for the diagnosis of tuberculosis were analyzed through double-blind readings by six professionals who usually read/supervise microscopies performed in public health care facilities. The sample was stratified to obtain, at least, a reliability of 90% in the double-blind readings, an alpha error of 5%, and a precision of 3%. The results were analyzed using observed reliability and the kappa index.', 'Thirteen errors (0.27%) were found in the transcription of results. Reliability increased when the three distinct categories of positive results (AFB+, AFB++, and AFB+++) were grouped or when inconclusive results were excluded from the analysis. The quantification of the bacterial load was the classification criterion that posed the most difficulty in establishing proficiency. Using higher quality microscopes increased reliability. Reliability values stabilized only from the reading of 75 microscopies onward.",
            "output": [
                "Does methodology for characterizing proficiency in interpreting sputum smear microscopy result in the diagnosis of tuberculosis?"
            ]
        },
        {
            "id": "task847-4d2e8170c581464f91beb3b21de2b6d1",
            "input": "We explored the clinical usefulness of serum carbonic anhydrase 9 as a potential biomarker for conventional renal cell cancer.', 'This study included 91 patients with conventional renal cell cancer and 32 healthy individuals. Enzyme linked immunosorbent assay was used to measure the carbonic anhydrase 9 level. A followup (median 38 months) was performed to track early recurrence after surgery for patients with localized disease. Recurrence-free survival curves were calculated by the Kaplan-Meier method and compared using the log rank test.', 'The mean serum carbonic anhydrase 9 level in patients with metastatic conventional renal cell cancer (216.68 +/- 67.02 pg/ml) or localized conventional renal cell cancer (91.65 +/- 13.29 pg/ml) was significantly higher than in healthy individuals (14.59 +/- 6.22 pg/ml, p <0.001 and p = 0.001, respectively). The mean serum carbonic anhydrase 9 level in patients with metastatic conventional renal cell cancer was significantly higher than in those with localized disease (p = 0.004). Of patients with localized disease those with recurrence had a significantly higher serum carbonic anhydrase 9 than those without recurrence (p = 0.001). On univariate analysis serum carbonic anhydrase 9, tumor stage, tumor grade and tumor size were associated with recurrence. The recurrence-free survival curve indicates that patients with a high serum carbonic anhydrase 9 level had a significantly higher recurrence rate than those with a low serum carbonic anhydrase 9 (p = 0.001).",
            "output": [
                "Is serum carbonic anhydrase 9 level associated with postoperative recurrence of conventional renal cell cancer?"
            ]
        },
        {
            "id": "task847-2648d9d9ab4b4b369725a837352cf910",
            "input": "The present analyses intend to clarify if gender and puberty modify the relationship between bone development (modeling and remodeling) and fat mass at the forearm.', 'Data were collected from participants (139 males, 157 females, age = 5-19 years) of the Dortmund Nutritional and Anthropometric Longitudinally Designed study in a cross-sectional investigation. The main outcome measures were total and trabecular bone mineral density (BMDtot and BMDtrab), strength strain index (SSI) and parameters associated with modeling (cortical area, CA; periosteal circumference, CP) and remodeling (cortical bone mineral density, BMDcort, endosteal circumference, CE) were analyzed in their relationship to cross-sectional fat (FA) and muscle area (MA) at the forearm.', 'BMDtot was correlated with FA in pubertal males (r = -0.25). BMDtrab was contrarily predicted by FA in pubertal males and females (r = -0.28 vs. 0.31). FA was correlated with BMDcort (r = -0.32) and CE (r = 0.26) in pubertal females. MA was positively correlated with CA, CP and SSI.",
            "output": [
                "Is local body composition associated with gender differences of bone development at the forearm in puberty?"
            ]
        },
        {
            "id": "task847-de50780d7d1c47b98401d988d8ab78c2",
            "input": "The short cold ischemic tolerance of the gut is a major problem in small bowel transplantation. We have shown that intestinal lipid administration is beneficial during systemic inflammation like sepsis.', 'Rats were intestinally infused with either water or 1% olive oil for 12 hours. The small bowel was removed and stored in HTK solution on ice. At t = 0, t = 60, t = 120, t = 180, t = 240, t = 300, t = 360, t = 420, and t = 480 minutes, a tissue sample of the gut was fixed, stained, and analyzed by three independent observers. Damage score was calculated (0 = no damage, 1 = minor damage, 2 = major damage, 3 = loss of structure) for integrity of the mucosa, integrity of the basal membrane of the mucosa, and integrity of villy. The damage score was allocated when all three observers agreed on the same or a higher damage score.', 'In all control animals minor damage for the integrity of the basal membrane occurred within 60 minutes, but in only 50% of the lipid-treated rats. In all control rats, major damage for both integrity of mucosa and villi occurred within 300 minutes or less, but only in 50% of the lipid-treated rats. In all control rats, the structure of the villi was completely lost within 480 minutes or less, whereas only 50% of the lipid treated animals reached maximal damage scores for either mucosa or villi.",
            "output": [
                "Does intestinal lipid absorption increase cold ischemia of the small bowel in rats?"
            ]
        },
        {
            "id": "task847-7af3e99bbdf54493ab30d137801a9bf2",
            "input": "Androgens cause regression of human hair follicles in the parietofrontal scalp, but the precise mechanisms by which they do so are unknown. Although many investigators have elucidated the effect of androgens on hair growth by using rodents and other animals, some of the evidence is conflicting.', 'To investigate the effect of androgens on mouse hair regrowth and hair cycle by using androgen receptor knockout (ARKO) mice. Methods We examined the effects of dihydrotestosterone (DHT) on hair regrowth by using ARKO mice and wild-type (WT) littermates, compared the hair cycles in ARKO mice and WT littermates by histology and histomorphometry, and measured hair length and thickness in ARKO mice and WT littermates.', 'DHT inhibited the hair regrowth of WT mice but not that of their ARKO littermates. The anagen phase in the second hair cycle was longer in ARKO mice than in their WT littermates. The hair of ARKO mice was longer and thicker than that of their WT littermates.",
            "output": [
                "Does dihydrotestosterone inhibit murine hair growth via the androgen receptor?"
            ]
        },
        {
            "id": "task847-fc6e5edd5fd846e89096359c84c41b22",
            "input": "We previously reported that prostatic stem/progenitor cells are concentrated in the proximal region of prostatic ducts and express stem cell antigen 1 (Sca-1). As Wnt signaling is important for the maintenance of stem cells, we determined whether Sca-1 expressing cells also express Axin2, as Axin2 expression is highly suggestive of active Wnt signaling.', 'Axin2 promoter reporter mice were used for whole mount and fluorescence activated cell sorting (FACS) analysis to determine its expression in the prostate. Axin2 expressing cells were also examined for the co-expression of Sca-1. We also used a chemical activator of Wnt signaling, BIO, to determine the effects of Wnt signaling on the growth of primary prostate cells in vitro.', 'We show that Axin2 expression is present in all lobes and is regulated by androgens with the highest Axin2 expression in the lateral and dorsal prostate. Furthermore, a fraction of Axin2 expressing cells co-express Sca-1, suggesting that some progenitor cells have active Wnt signaling. Lastly, we demonstrate that activation of the Wnt pathway may result in increased growth, consistent with a role for Wnt signaling in maintenance and/or expansion of the progenitor cell population.",
            "output": [
                "Does axin2 expression identify progenitor cells in the murine prostate?"
            ]
        },
        {
            "id": "task847-3ddabfc7e89b455893056c5f78dfd60c",
            "input": "Alterations in serum lipids and an increased risk of myocardial infarction have been associated with HIV-1 infection and its treatment.', 'Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy in frozen plasma samples from participants in the Multicenter AIDS Cohort Study. The effects of HIV-1 infection, antiretroviral therapy, and other factors on median particle concentrations were examined using quantile regression.', 'Fasted samples were tested from 1082 men, including 609 HIV-seronegative and 473 HIV-1-infected men. Compared with HIV-seronegative men, HIV-1-infected men on antiretroviral therapy had an atherogenic phenotype with higher numbers of very low density lipoprotein and small low-density lipoprotein particles and lower numbers of high-density lipoprotein and large low-density lipoprotein particles. HIV-infected, antiretroviral-naive men had significantly lower high-density lipoprotein and small low-density lipoprotein particle concentrations compared with the HIV-seronegative men. Among men on antiretroviral therapy, the atherogenic phenotype was most pronounced in men with a good clinical status.",
            "output": [
                "Is antiretroviral therapy associated with an atherogenic lipoprotein phenotype among HIV-1-infected men in the Multicenter AIDS Cohort Study?"
            ]
        },
        {
            "id": "task847-a78e5571cc684a3baf7f07938f48b0f1",
            "input": "To examine the role of mitogen-activated protein kinase-activated protein kinase 2 (MK2) in mediating the cellular response to pro-inflammatory cytokines in human primary osteoarthritis (OA) chondrocytes.', 'Delivery of a dominant negative MK2 was achieved in HeLa cells by adenoviral infection. Cellular heat shock protein (HSP27) activity was determined using a Bioplex assay. Primary OA chondrocytes were isolated by collagenase digestion of human articular cartilage. Phosphorylated MK2 was detected by immunoblotting and immunohistology. Transfection of primary chondrocytes with siRNA was achieved using cationic lipid and gene expression determined by real-time polymerase chain reaction. Production of prostaglandin E2 (PGE2) and matrixmetalloproteases (MMPs) was measured by enzyme-linked immunosorbent assay.', 'Over-expression of a dominant negative MK2 inhibited HSP27 phosphorylation and significantly reduced both interleukin 1 (IL-1)beta and tumour necrosis factor (TNF)-alpha mediated release of PGE2 in HeLa cells over a 24h period. Phosphorylated MK2 was detected in OA articular cartilage and in isolated primary OA chondrocytes, where it was induced by IL-1beta. Transfection of OA chondrocytes with MK2 siRNA antisense significantly reduced both basal and IL-1beta induced PGE2 release. siRNA mediated MK2 knockdown also significantly reduced both basal and IL-1beta induced MMP13 expression and MMP13 and MMP3 protein release but had no effect on MMP1.",
            "output": [
                "Does mitogen-activated protein kinase-activated protein kinase 2 ( MK2 ) modulate key biological pathways associated with OA disease pathology?"
            ]
        },
        {
            "id": "task847-b87e5f0871174c53b374ade374f1b1db",
            "input": "CD40 and its ligand, CD154, play a regulatory role in several signaling pathways among lymphocytes. Recently, it was reported that CD40 is expressed in several malignant tumors. However, the clinical impact of CD40 expression in nonsmall cell lung cancer has not been studied widely.', \"One hundred twenty-nine surgical specimens of nonsmall cell lung cancer were assessed immunohistochemically for CD40 and CD154 expression, and that expression was correlated with patients' clinicopathologic parameters and outcome. Subsequently, in vitro analysis of CD40-CD154 signaling was performed.\", 'Immunohistochemical staining of tumor cells confirmed that 67 patients (51.9%) were positive for CD40, and 76 patients (58.9%) were positive for CD154. The survival of patients who had tumors that were negative for CD40 was significantly better than the survival of patients who had tumors that were positive for CD40 (P = .0004). Multivariate analysis using a Cox regression model indicated that CD40 expression in cancer cells is an independent, unfavorable prognostic factor (risk ratio, 1.855; P = .0403). By using an in vitro juxtacrine growth factor assay, the growth of LK2 cells (CD40-positive/CD154-negative) was accelerated by CD154-positive cancer cells, such as PC10 cells (CD40-negative/CD154-positive), by a juxtacrine mechanism.",
            "output": [
                "Does up-regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlate with poor prognosis?"
            ]
        },
        {
            "id": "task847-3510e92164224e199dbf73866a9eb821",
            "input": "To describe the clinical and genetic characteristics of the second family with a recently described recessive syndrome characterized by posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disk drusen.', 'Observational case report.', 'Three affected subjects and one healthy sibling from a consanguineous marriage from Spain were studied. Complete ophthalmologic examinations including A- and B-mode ultrasonography (US), electroretinography (ERG), fluorescein retinal angiography (FA), and optical coherence tomography (OCT) were performed in each individual. Genetic analysis included polymerase chain reaction amplification and direct nucleotide sequencing of the complete MFRP gene.', 'All three affected siblings had bilateral shortening of the posterior ocular segment associated with high hyperopia and normal anterior segment dimensions. Best-corrected visual acuity ranged from 20/200 to 20/60. Funduscopy, ERG, and FA were compatible with retinitis pigmentosa, and B-mode ultrasound showed optic disk drusen. OCT analysis revealed outer retinal layer schisis with absence of foveal pit. Inheritance of this syndrome followed an autosomal recessive pattern. Molecular analysis revealed a novel homozygous 1-bp deletion (c.498delC) in exon 5 of MFRP, predicting a prematurely truncated protein (P166fsX190). A healthy sister demonstrated to be a carrier of the mutation.",
            "output": [
                "Does a novel mutation confirm MFRP as the gene causing the syndrome of nanophthalmos-renititis pigmentosa-foveoschisis-optic disk drusen?"
            ]
        },
        {
            "id": "task847-848920ece09641479a7c27a52aab277b",
            "input": "Periodontal ligament (PDL) cells express oestrogen receptors but the functional importance of oestrogen in PDL cells exposed to bacterial endotoxins is not known. Here we investigate if the inflammation promoter lipopolysaccharide (LPS) affects PDL cell production of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and/or normal functional PDL cell characteristics such as collagen synthesis and cell proliferation and if oestrogen modulates the effects of LPS.', 'PDL cells were obtained from periodontal ligament of premolars. PDL cells were treated with Escherichia coli LPS in the absence or presence of oestrogen (17beta-oestradiol, E2). Cellular concentration of IL-6, MCP-1 and CRP was determined by enzyme-linked immunosorbent assay (ELISA). Collagen synthesis was determined by l-[3H]proline incorporation. Cell proliferation was assessed by DNA synthesis measurement using [3H]thymidine incorporation.', 'Stimulation with LPS (500 ng/ml to 10 microg/ml) increased IL-6 production in a concentration-dependent manner. Lower concentration (100 ng/ml) of LPS had no effect. LPS-induced stimulation of IL-6 was not reversed by a physiologically high concentration (100 nM) of E2. LPS increased also MCP-1 production which was unaffected by E2. Treatment with E2 alone had no effect on either IL-6 or MCP-1. Stimulation with LPS had no effect on CRP. LPS did not affect collagen synthesis and cell proliferation, reflecting normal physiological properties of PDL cells.",
            "output": [
                "Is lPS-induced MCP-1 and IL-6 production reversed by oestrogen in human periodontal ligament cells?"
            ]
        },
        {
            "id": "task847-6c20b4a76e4c4238b4da854b7586c603",
            "input": "The aim of this study is to evaluate if it is necessary to remove all the radioactive sentinel lymph nodes (SLNs) not seen on lymphoscintigraphy in order to accurately stage breast cancer patients.', 'From March 1999 to March 2006, SLN biopsy was performed in 461 patients. All patients were only injected with radioisotope. Lymphoscintigraphy was performed in all the patients. The mean number of SLNs removed was 2.1 (range 1-15).', 'The SLN was positive in 133 patients (28.8%). Lymphoscintigraphy accurately predicted the number of SLNs identified intraoperatively in 243 patients (52.7%). In 175 patients (37.9%) there were more SLNs identified intraoperatively than were seen on lymphos cintigraphy. In 11 (6.2%) of these 175 patients, additional SLNs identified intraoperatively harboured metastasis. Type of injection, need for a second injection, tumour location and age were not identified as statistically significantly associated with additional positive SLNs identified intraoperatively and not seen on lymphoscintigraphy.",
            "output": [
                "Does removal of all radioactive sentinel nodes in breast cancer improve the detection of positive sentinel nodes?"
            ]
        },
        {
            "id": "task847-3d27d2136b83409c82c912a679d08193",
            "input": "Parameters of MR imaging play a pivotal role in diagnosing lumbar spinal stenosis (LSS), and serve as an important tool in clinical decision-making. Despite the importance of MR imaging, little is known about the correlation between MRI parameters, objective gait analysis, and clinical presentation of patients with lumbar spinal stenosis.', 'Sixty-three patients from our clinic with symptomatic lumbar spinal stenosis leading to neurogenic claudication were included in this study in accordance with clearly defined inclusion and exclusion criteria. Clinical parameters, the depression status (CES-D), the subjective functional back capacity (FFbH-R), and the absolute walking distance (treadmill gait analysis) were quantitatively evaluated in correlation with morphological data from radiographs and MRI scans, in order to determine the coherence of spinal canal narrowing and clinical affliction.', 'Sixty-three consecutive paents with a median age of 68 years and a mean Body Mass Index (BMI) of 28 were included in the study. The mean FFbH-R score displayed a value of 44 percent. The depression status scored an average of 13.6. Objectively measured walking distances showed a mean value of 172 m until patients stopped due to leg pain. A significant difference was found between the objectively measured and the subjectively estimated walking distance. The mean cross-sectional area of the dural tube at L1/2 was 113 mm2, at L2/3 94 mm2, at L3/4 73 mm2, at L4/5 65 mm2, and at L5/S1 93 mm2. The mean overall cross sectional area of the dural tube of all segments did not correlate with the objectively measured walking distance. However, bivariate analysis found that the BMI (tau b = -0.194), functional back capacity (tau b = -0.225), and the cross sectional area of the dural tube at L1/2 (tau b = -0.188) correlated significantly with the objectively measured walking distance.",
            "output": [
                "Does gait analysis correlate with clinical and MR imaging parameters in patients with symptomatic lumbar spinal stenosis?"
            ]
        },
        {
            "id": "task847-6201a6fd41134ede8618abaa66325707",
            "input": "Pancreatic cancer is a very aggressive malignancy and efficient therapeutic options are still largely lacking. The importance of interactions between tumor cells and surrounding stromal elements, eg, mononuclear cells, for chemoresistance have been increasingly recognized. In addition, cyclooxygenase-2 is thought to be an important mediator of chemoresistance in several malignancies. The aim of this study was to explore the role of mononuclear cells in pancreatic cancer chemoresistance.', 'Human histiocytic lymphoma U937 cells were differentiated into macrophage-like cells. The effect of U937-conditioned medium on drug-induced pancreatic cancer cell apoptosis was measured by enzyme-linked immunosorbent assay. The contributions of interleukin-1beta and cyclooxygenase-2 were evaluated by specific receptor antagonists and inhibitors. The importance of the extracellular signal-regulated kinase (ERK1/2) pathway also was determined.', 'U937-conditioned culture medium protected pancreatic cancer cells from drug-induced apoptosis. This protective effect was abolished by an interleukin-1 receptor antagonist and cyclooxygenase-2 inhibitor. U937-conditioned medium and interleukin-1beta stimulated expression of cyclooxygenase-2 and prostaglandin E(2) production in pancreatic cancer cells, which was mediated by activation of the ERK1/2 pathway. Transfection of pancreatic cancer cells with cyclooxygenase-2 increased resistance to drug-induced cell death.",
            "output": [
                "Does mononuclear cell-derived interleukin-1 beta confer chemoresistance in pancreatic cancer cells by upregulation of cyclooxygenase-2?"
            ]
        },
        {
            "id": "task847-6c9ca1eeb2ba4e458c3990343515602c",
            "input": "Stable polyamine homeostasis is important for cell survival and regeneration. Our experimental studies have shown that catabolism of spermidine and spermine to putrescine is associated with the development of pancreatitis. We investigated the pathogenetic role of polyamine catabolism by studying the effect of a methylated polyamine analog on taurodeoxycholate-induced acute experimental pancreatitis.', 'Acute pancreatitis was induced by infusion of sodium taurodeoxycholate (2%) into the pancreatic duct. Bismethylspermine (Me(2)Spm) was administered as a pretreatment before the induction of pancreatitis or as a treatment after the induction of pancreatitis. The sham operation included laparotomy only. Pancreas tissue and blood were sampled at 24 h and 72 h after the infusion of taurodeoxycholate and studied for pancreatitis severity (serum amylase activity, pancreatic water content, and histology) and polyamine catabolism, which includes spermidine/spermine N(1)-acetyltransferase (SSAT) activity as well as spermidine, spermine, and putrescine concentrations in the pancreas.', 'Sodium taurodeoxycholate-induced acute pancreatitis manifests as increases in serum amylase and pancreatic water content, leukocytosis, and acinar cell necrosis in the pancreas. The activity of SSAT increased significantly together with an increase in the ratios of pancreatic putrescine/spermidine and putrescine/spermine at 24 h, which indicates SSAT-induced polyamine catabolism. Pancreatic water content and necrosis were reduced significantly by the treatment with Me(2)Spm at 24 h but not at 72 h when the polyamine homeostasis had recovered, and the pancreatitis had progressed.",
            "output": [
                "Does a polyamine analog bismethylspermine ameliorate severe pancreatitis induced by intraductal infusion of taurodeoxycholate?"
            ]
        },
        {
            "id": "task847-e87a68cdbc724735919f4991cfbd8f30",
            "input": "Prevention of intraabdominal abscess formation constitutes an important goal in treatment of secondary peritonitis. Fibrinolytic therapy may be effective in this respect. The efficacy of recombinant tissue plasminogen activator (rtPA) and urokinase is compared in a preclinical model for surgical treatment of peritonitis.', 'Peritonitis was induced by intraperitoneal bacterial challenge in male Wistar rats. After 1 hour, surgery was performed. Four groups (n = 20) were treated with one of the following: rtPA, urokinase, streptokinase (a negative protein control), or saline. Blood cultures were taken at 6 and 24 hours; cell counts and cytokine measurements were performed in peritoneal fluid at 1, 3 and 5 days. After 5 days, animals were killed and intraperitoneal abscess formation was analyzed.', 'Both rtPA and urokinase strongly (> 75%) and significantly (P < .05) reduced abscess formation without negative side effects. No bleeding complications were observed. Fibrinolytic therapy altered the intraperitoneal cellular distribution (less neutrophils and more macrophages) but did not essentially alter the courses of interleukin-6 and interleukin-10 (decreasing in time) or tumor necrosis factor-* (increasing in time) levels.",
            "output": [
                "Do both tissue-type plasminogen activator and urokinase prevent intraabdominal abscess formation after surgical treatment of peritonitis in the rat?"
            ]
        },
        {
            "id": "task847-d02bbfcc2cc1436fb614d012526f65c6",
            "input": "The combination of hepatic ischemia and cholestasis, both identified as risk factors for oxidative stress, potentially enhances postischemic reperfusion (I/R) injury. Preoperative biliary drainage relieves oxidative stress and therefore seems a worthwhile intervention in cholestatic patients undergoing major liver resection.', 'To assess the effect of biliary decompression on I/R injury in a reversible bile duct ligation (BDL) model in the rat.', 'Male Wistar rats were randomized into 3 groups. The first group underwent 30 minutes of partial liver ischemia after 7 days BDL; the second group underwent internal drainage (ID) after 7 days BDL and after 5 days, were subjected to partial liver ischemia. The last group (control animals) underwent 2 sham laparotomies and subsequent ischemia. Inflammatory response (interleukin [IL]-6, IL-10, GRO/KC, and interferon-gamma), hepatic damage and oxidative stress were assessed during 24 hours of reperfusion.', 'Cholestatic rats, as compared with the ID and control groups, showed significantly increased I/R injury as determined by transaminase release, histologic injury score and neutrophil infiltration. Plasma IL-6, IL-10, and GRO/KC (a CXC chemokine) were significantly increased in the BDL group (P < .05 vs control and ID). Moreover, the hepatic antioxidant capacity was strongly decreased in the BDL group (P < .01 vs control and ID). No significant differences for most parameters were seen in the ID group as compared to the control group.",
            "output": [
                "Does biliary drainage attenuate postischemic reperfusion injury in the cholestatic rat liver?"
            ]
        },
        {
            "id": "task847-ef8adf34ef1c4d2a9e7639b139e8aa82",
            "input": "Free fat grafts have an unpredictable survival rate, which may be dependent on host bed vascularity. Therefore, the authors hypothesized that the presence of growth factors in platelet-rich plasma (PRP), may enhance free fat graft survival.', 'Free fat grafts and autologous PRP were harvested from a healthy female and processed using the Coleman technique and the Medtronic Magellan system respectively. The experiment comprised two groups of 12 nude mice each with injection of free fat grafts into the scalp. The experimental group comprised the combination of 0.8 ml of free fat graft and 0.2 ml of PRP. The control group comprised the combination of 0.8 ml of free fat graft and 0.2 ml of normal saline. The mice were euthanized after 16 weeks and the fat grafts explanted and measured for weight and volume. Histology was performed with Oil Red O stain. Statistical analysis of the weight and volume in between groups was performed using the independent samples T-test (SPSS v11). The Mann-Whitney test was used to compare the ranking of six histological parameters between the two groups.', 'The mean weight and volume for the experimental arm were 0.503 g and 0.545 ml respectively. The mean weight and volume for the control arm were 0.500 g and 0.541 ml respectively. The weight, volume and histological parameters between the two groups were not statistically significant. A mouse from each group died of unknown causes.",
            "output": [
                "Does platelet-rich plasma have no effect on increasing free fat graft survival in the nude mouse?"
            ]
        },
        {
            "id": "task847-06795e8f6eee40ec9ff3e66820a80ecb",
            "input": "Poor power quality (dirty electricity) is ubiquitous especially in schools with fluorescent lights and computers. Previous studies have shown a relationship between power quality and student behavior/teacher health.', 'The purpose of this study is to determine the ability of power line filters to reduce dirty electricity in a school environment and to document changes in health and behavior among teachers and students.', 'We installed Graham Stetzer filters and dummy filters and measured power quality in three Minnesota Schools. Teachers completed a daily questionnaire regarding their health and the behavior of their students for an 8-week period. Teachers were unaware of which filters were installed at any one time (single blind study).', 'Dirty electricity was reduced by more than 90% in the three schools and during this period teacher health improved as did student behavior in the middle/elementary schools. Headaches, general weakness, dry eyes/mouth, facial flushing, asthma, skin irritations, overall mood including depression and anxiety improved significantly among staff. Of the 44 teachers who participated 64% were better, 30% were worse, and 6% did not change. Behavior of high school students did not improve but elementary/middle school students were more active in class; more responsive, more focused; had fewer health complaints; and had a better overall learning experience.",
            "output": [
                "Does power quality affect teacher wellbeing and student behavior in three Minnesota Schools?"
            ]
        },
        {
            "id": "task847-693e865f901a4bacb45fb29675192739",
            "input": "To retrospectively assess the relationship between carotid intraplaque hemorrhage (IPH), which indicates plaque instability, and brain white matter hyperintense lesions (WMHLs) by using a within-patient design.', 'All patients gave written informed consent for the initial magnetic resonance (MR) studies, and the institutional review board and local research ethics committee waived initial informed consent for the pooled analysis. A total of 190 patients with symptomatic carotid artery disease underwent fluid-attenuated inversion-recovery imaging of the brain and fat-suppressed black-blood T1-weighted MR imaging of the carotid arteries. The volumes of periventricular lesions, subcortical lesions, and total WMHLs were calculated and compared between hemispheres in relation to symptoms and IPH, and their interaction was calculated and compared by using repeated measures three-factorial multivariate analysis.', 'After exclusion of 12 patients, 178 patients (116 men, 62 women; mean age, 70.2 years +/- 8.6 [standard deviation]) remained. There was no significant difference in WMHL volume between the symptomatic and asymptomatic hemispheres, and WMHL volume was not related to the degree of carotid stenosis. The presence of carotid IPH significantly interacted with the interhemispheric WMHL difference (Wilks lambda test, F = 9.95; df = 3; P < .001). Univariate analysis showed larger total and periventricular WMHL volumes (P < .05) in patients with ipsilateral IPH.",
            "output": [
                "Are brain white matter hyperintensities associated with carotid intraplaque hemorrhage?"
            ]
        },
        {
            "id": "task847-ec437bfa29004142af09fa0caf2fee99",
            "input": "Plasminogen activator inhibitor-1 (PAI-1) has been shown to increase after percutaneous coronary intervention (PCI). Whether activated platelets, local trauma with activation of resident vascular cells or the acute phase response is the source of this PAI-1 increase is not well defined. Therefore we examined whether intensive platelet inhibition may modulate PAI-1 levels or whether the PAI-1 increase is associated with the acute phase protein C-reactive protein (CRP).', 'We included 51 patients with stable angina who underwent elective PCI with stent implantation. At the time of study, routine pretreatment with clopidogrel before PCI was not standard of care, but left to the discretion of the referring cardiologist. We matched 17 patients with stable angina that were not pretreated with clopidogrel but received a loading dose of 300 mg immediately after stent implantation according age, sex and smoking with 34 patients that received clopidogrel at least 12 to 24 hours before PCI. Blood samples for measurement of PAI-1, t-PA and CRP were taken directly before and 24 hours after the procedure.', 'PAI-1 and t-PA active antigen plasma levels before PCI were not different in patients with and without clopidogrel pretreatment. Whereas PCI induced a significant increase of PAI-1 levels in patients without pretreatment (p<0.05), the procedure had no effect on PAI-1 active antigen in patients pretreated with clopidogrel. This resulted in significant lower PAI-1 plasma levels 24 hours after PCI in patients with pretreatment (p<0.05). CRP was not associated with pre- or postprocedural PAI-1 levels.",
            "output": [
                "Does clopidogrel pretreatment abolish increase of PAI-1 after coronary stent implantation?"
            ]
        },
        {
            "id": "task847-1e4e0918f2b14100a8914001b10b3a44",
            "input": "The efficacy of anti-tumour necrosis factor-alpha (TNF-alpha) therapies in rheumatoid arthritis (RA) has been mainly attributed to TNF-alpha neutralisation. Other mechanism as immune cell apoptosis, which is impaired in RA, may also be induced by anti-TNF-alpha therapies. The aim of our study was to investigate whether TNF-alpha inhibitors could induce apoptosis in vitro of the peripheral blood lymphocytes of RA patients.', 'Peripheral blood mononuclear cells (PBMC) isolated from 24 patients with RA and 18 healthy donors were incubated with anti-TNF-alpha agents, infliximab or etanercept, in comparison with no agent and including an isotypic control, for 48 hours. Apoptosis was detected and quantified by annexin V labelling of phosphatidylserine externalization using cytofluorometric analysis and compared with PBMC production TNF-alpha in vitro.', 'In healthy donors, induced apoptosis was observed in 0.3% to 3.8% of lymphocytes with both therapies. In RA patients the treatment induced lymphocyte apoptosis in 17 of 24 patients with a percentage of annexin V-positive lymphocytes ranging from 0.1% to 25%. Among these 17 RA patients, a significant in vitro lymphocyte apoptosis (> 4%) was observed in 11 patients (46%) compared with healthy donors (p < 0.01). The variability of the response to anti-TNF-alpha within the RA population was not dependent on TNF-alpha synthesis or disease activity.",
            "output": [
                "Are peripheral blood lymphocytes from patients with rheumatoid arthritis differentially sensitive to apoptosis induced by anti-tumour necrosis factor-alpha therapy?"
            ]
        },
        {
            "id": "task847-181b0fc3b9434b28b9d62f01b6f1b533",
            "input": "Stem cell factor (SCF) has well-known proliferative effects on hematopoietic cells. SCF also has effects on differentiation and proliferation in other cell types. Interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha have proliferative effects in the liver. Recent studies in our laboratory have linked SCF's hepatoproliferative actions to those of IL-6, demonstrating that IL-6-induced hepatocyte proliferation depends, at least in part, on SCF. We now hypothesize that TNF-alpha's hepatoproliferative effects are also dependent on SCF.\", 'In vitro studies using primary mouse hepatocytes show that SCF is induced by TNF-alpha; anti-SCF antibody treatment in this system inhibits TNF-alpha-induced hepatocyte proliferation, suggesting that TNF-alpha-induced hepatocyte proliferation is also SCF dependent. Additional in vivo experiments were performed in which wild type and/or TNF-alpha receptor-1 knockout mice (TNFR1(-/-)) were subjected to 70% hepatectomy or sham laparotomy. TNFR1(-/-) mice are known to have delayed hepatic regeneration after partial hepatectomy. Initial experiments demonstrated that the SCF receptor, c-kit, is upregulated after partial hepatectomy in wild-type mice, further emphasizing the importance of this system in the restoration of hepatic mass. SCF administration to TNFR1(-/-) mice in the context of partial hepatectomy restores hepatocyte proliferation to normal. Further, SCF administration to TNFR1(-/-) mice before hepatectomy increases phosphotyrosine signal transducer and activator (p-stat-3) levels, suggesting that SCF-induced increases in hepatocyte proliferation may also be stat-3 mediated.",
            "output": [
                "Are stem cell factor and its receptor , c-kit , important for hepatocyte proliferation in wild-type and tumor necrosis factor receptor-1 knockout mice after 70 % hepatectomy?"
            ]
        },
        {
            "id": "task847-a463d15991d2458fa29bed67897189fc",
            "input": "Intestinal transport exhibits distinct diurnal rhythmicity. Understanding the mechanisms behind this may reveal new therapeutic strategies to modulate intestinal function in disease states such as diabetes and obesity, as well as short bowel syndrome. Although diurnal rhythms have been amply documented for several intestinal transporters, the complexity of transepithelial transport has precluded definitive attribution of rhythmicity in glucose uptake to a single transporter. To address this gap, we assessed temporal changes in glucose transport mediated by the Na(+)/glucose cotransporter SGLT1.', 'SGLT1 expression was assessed at 4 times during the day: ZT3, ZT9, ZT15, and ZT21 (ZT, Zeitgeber time; lights on at ZT0; n = 8/ time). SGLT1 activity, which is defined as glucose uptake sensitive to the specific SGLT1 inhibitor phloridzin, was measured in everted intestinal sleeves. Changes in Sglt1 expression were assessed by real-time polymerase chain reaction (PCR) and immunoblotting.', 'Glucose uptake was significantly higher at ZT15 in jejunum (P < 0.05 vs ZT3). Phloridzin significantly reduced glucose uptake and completely abolished its rhythmicity. Sglt1 mRNA levels were significantly greater at ZT9 and ZT15 in jejunum and ileum, respectively (P < 0.05 vs ZT3), whereas SGLT1 protein levels were significantly greater at ZT15 in jejunum (P < 0.05 vs ZT3).",
            "output": [
                "Is diurnal rhythmicity in glucose uptake mediated by temporal periodicity in the expression of the sodium-glucose cotransporter ( SGLT1 )?"
            ]
        },
        {
            "id": "task847-b8b52be0fb0f445890832b1df79c14d4",
            "input": "Hox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern-specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial, and cellular expression of Hoxa5, Hoxb4, and Hoxb6 proteins compared to normal lung development.', 'Temporal, spatial, and cellular Hoxa5, Hoxb4, and Hoxb6 expression was studied in normal (untreated) and nitrofen-induced hypoplastic (NT-PH) lungs from gestational day 13.5, 16, and 19 fetuses and neonates using Western blot and immunohistochemistry.', 'Modification of protein levels and spatial and cellular Hox expression patterns in NT-PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 protein isoforms changed with development and were altered further in NT-PH lungs. Compared to normal lungs, GD19 and neonatal NT-PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways.",
            "output": [
                "Are unique spatial and cellular expression patterns of Hoxa5 , Hoxb4 , and Hoxb6 proteins in normal developing murine lung modified in pulmonary hypoplasia?"
            ]
        },
        {
            "id": "task847-57560c2a4a9a4aa199d708a0f84b32dc",
            "input": "To investigate the effect of therapeutic hypothermia in the prognostic value of the pituitary-adrenal axis in comatose patients after cardiac arrest.', 'Prospective observational study in intensive care units (ICU) of a university and an affiliated regional hospital.', 'Twenty-nine consecutive patients, in coma after cardiac arrest, admitted to the ICU and treated by hypothermia.', 'On ICU-admission (T=1), at reaching the target of 32-33 degrees C during therapeutic hypothermia (T=2), at the end of hypothermia (T=3) and 48h later (T=4), plasma adrenocorticotrophic hormone (ACTH), serum cortisol, albumin and corticosteroid-binding globulin (CBG) were measured. A short 250 microg ACTH test was performed at each time-point, except at T=1. The free cortisol index (FCI) and free cortisol calculated by Coolens method were also evaluated.', 'The ICU mortality was 59%, including withdrawal of life-sustaining treatment in 45% because of negative somatosensory evoked potentials. ACTH and (free) cortisol levels (mean 13.1 pmol/L vs. 6.0 pmol/L and 1250 nmol/L vs. 596 nmol/L, respectively) were higher in non-survivors than in survivors. Levels decreased in time, but the relative difference between outcome groups was maintained until T=4. The cortisol response to ACTH was lower in non-survivors at T=3 (P=0.047) only.",
            "output": [
                "Is the pituitary-adrenal axis activated more in non-survivors than in survivors of cardiac arrest , irrespective of therapeutic hypothermia?"
            ]
        },
        {
            "id": "task847-6b18e2204ad24bc3851f201ce29094d3",
            "input": "Hemodialysis (HD) is associated with significant reductions in the plasma concentrations of the nitric oxide (NO) inhibitors N(G)-monomethyl L-arginine (L-NMMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). We sought to determine whether elevated concentrations of these NO inhibitors pre-HD and/or their acute decrease during HD might mediate intradialytic hypotension (IDH).', 'Systolic blood pressure (SBP), L-arginine, L-NMMA, ADMA, and SDMA were measured at the beginning (pre-HD) and at the end (end-HD) in 52 consecutive HD patients (age 64.4 +/- 13.4 years). IDH was defined as a SBP reduction of >20 mm Hg end-HD vs. pre-HD.', 'Fourteen patients demonstrated IDH. The mean SBP reduction during HD in this group was -35 +/- 13 mm Hg compared to an increase of +2 +/- 12 mm Hg among the 38 patients without IDH (no-IDH). Baseline demographic, clinical, and biochemical parameters did not differ between the IDH and no-IDH groups. However, the IDH group had higher pre-HD SBP (155 +/- 17 vs. 132 +/- 14 mm Hg, P < 0.001), pre-HD plasma SDMA concentrations (1.98 +/- 0.61 vs. 1.64 +/- 0.46 micromol/l, P = 0.04), and greater SDMA reductions during HD (-0.78 +/- 0.43 vs. -0.56 +/- 0.32 micromol/l, P = 0.06) than the no-IHD group. After adjusting for pre-HD SBP, the odds of IDH occurring were higher with increased pre-HD SDMA plasma concentrations (OR = 1.31 per 0.1 micromol/l SDMA increase; 95% CI = 1.04-1.65, P = 0.02) and with decreases in SDMA during HD (OR = 1.39 per 0.1 micromol/l SDMA decrease; 95% CI = 1.02-1.91, P = 0.04).",
            "output": [
                "Is symmetric dimethylarginine an independent predictor of intradialytic hypotension?"
            ]
        },
        {
            "id": "task847-f6c8eb7de90c443dbbd05ea88af9865a",
            "input": "We performed genetic association studies using a native Japanese population to examine the reproducibility of results of lysyl oxidase-like 1 (LOXL1) genetic association studies for exfoliation glaucoma (XFG) beyond the differences of ethnicity. We also quantified LOXL1 mRNA expression in the human lens capsule to examine the possible correlation between LOXL1 expression and XFG pathogenesis.', 'We performed a case-control study using 95 Japanese XFG patients and 190 controls. Real-time polymerase chain reaction (PCR) analysis was performed using lens capsules obtained during surgery.', 'The TT genotype in the single nucleotide polymorphism (SNP) rs1048661 and the GG genotype in the SNP rs3825942 in exon 1 of LOXL1 were significantly associated with an increased risk of XFG under recessive models (chi(2) test, p=5.34 x 10(-34) and p=2.1 x 10(-8), respectively). Quantification of LOXL1 mRNA expression demonstrated no significant difference between XFG and senile cataract samples.",
            "output": [
                "Are lOXL1 genetic polymorphisms associated with exfoliation glaucoma in the Japanese population?"
            ]
        },
        {
            "id": "task847-1a1a256f71b940a88256cee0086ed859",
            "input": "Mast cells (MC) are key effector cells of allergic diseases and resistance to helminthic parasites and induce or amplify diverse innate and adaptive immune responses. The signals controlling MC mobilization during inflammation are not fully understood.', 'Since anaphylatoxins are attractive candidates as MC chemoattractants, we investigated expression and function of anaphylatoxin receptors in murine MC. Precursor cell-derived MC cultured with IL-3 in the presence or absence of SCF did not express significant amounts of surface C5a receptor (C5aR) or C3a receptor (C3aR). MC required approximately 4 h of stimulation with Ag (DNP-albumin, following preincubation with IgE anti-DNP), ionomycin, or PMA to enable a strong chemotactic response towards C5a, paralleled by a distinct C5aR upregulation. Likewise, C5a induced intracellular calcium fluxes solely in activated MC. In contrast, C3a proved to be a weak MC chemotaxin and unable to increase intracellular calcium. Primary peritoneal MC did not express detectable amounts of anaphylatoxin receptors, however, similar to precursor cell-derived MC, stimulation with Ag or ionomycin for 4 h induced a prominent surface expression of C5aR whereas C3aR remained undetectable.",
            "output": [
                "Is mast cell activation characterized by upregulation of a functional anaphylatoxin C5a receptor?"
            ]
        },
        {
            "id": "task847-8ba2837ec9294f0eba1de1156c99c1bc",
            "input": "Human breast tumors are heterogeneous and consist of phenotypically diverse cells. Breast cancer cells with a CD44+/CD24- phenotype have been suggested to have tumor-initiating properties with stem cell-like and invasive features, although it is unclear whether their presence within a tumor has clinical implications. There is also a large heterogeneity between tumors, illustrated by reproducible stratification into various subtypes based on gene expression profiles or histopathological features. We have explored the prevalence of cells with different CD44/CD24 phenotypes within breast cancer subtypes.', 'Double-staining immunohistochemistry was used to quantify CD44 and CD24 expression in 240 human breast tumors for which information on other tumor markers and clinical characteristics was available. Gene expression data were also accessible for a cohort of the material.', 'A considerable heterogeneity in CD44 and CD24 expression was seen both between and within tumors. A complete lack of both proteins was evident in 35% of the tumors, while 13% contained cells of more than one of the CD44+/CD24-, CD44-/CD24+ and CD44+/CD24+ phenotypes. CD44+/CD24- cells were detected in 31% of the tumors, ranging in proportion from only a few to close to 100% of tumor cells. The CD44+/CD24- phenotype was most common in the basal-like subgroup--characterized as negative for the estrogen and progesterone receptors as well as for HER2, and as positive for cytokeratin 5/14 and/or epidermal growth factor receptor, and particularly common in BRCA1 hereditary tumors, of which 94% contained CD44+/CD24- cells. The CD44+/CD24- phenotype was surprisingly scarce in HER2+ tumors, which had a predominantly CD24+ status. A CD44+/CD24- gene expression signature was generated, which included CD44 and alpha6-integrin (CD49f) among the top-ranked overexpressed genes.",
            "output": [
                "Does the CD44+/CD24- phenotype is enriched in basal-like breast tumors?"
            ]
        },
        {
            "id": "task847-069835fd922947dabc22e1beb28986e1",
            "input": "Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that is implicated in the pathogenesis of several postoperative complications. Studies have shown that proinflammatory cytokines are increased by acute hyperglycemia. Recent evidence suggests that insulin has antiinflammatory properties. Therefore, we hypothesized that high-dose insulin therapy would attenuate the systemic inflammatory response to cardiopulmonary bypass and surgery in coronary artery bypass patients while maintaining normoglycemia.', 'A total of 52 patients who presented for elective coronary artery bypass were randomized to receive intraoperative intravenous insulin infusion, titrated to maintain blood glucose concentrations less than 180 mg/dL (group I, n = 25), or receive intraoperative fixed high dose of intravenous insulin infusion (5 mU/kg/min) with dextrose 20% infused separately to maintain a blood glucose level between 70 and 110 mg/dL (group II, n = 27). Blood samples were collected at different time points to determine tumor necrosis factor alpha (TNFalpha), interleukin 6 and 8 (IL6 and IL8), and complement factor 3 and 4 (C3 and C4).', 'Patients in both groups had similar preoperative characteristics. Patients in the high-dose insulin group had higher blood insulin concentrations and tighter blood glucose control. There were lower levels of IL6 (150 pg/dL vs 245 pg/dL, p = 0.03), IL-8 (49 pg/dL vs 74 pg/dL, p = 0.05), and TNFalpha (2.2 pg/dL vs 3.0 pg/dL, p = 0.04) in group II in the early postoperative period.",
            "output": [
                "Does high-dose insulin therapy attenuate systemic inflammatory response in coronary artery bypass grafting patients?"
            ]
        },
        {
            "id": "task847-e2d740c2313a41ae91ce12277ad2e38d",
            "input": "Critical size defects (CSDs) of bone are defined as defects that do not heal spontaneously to new bone during the lifetime of an adult individual. In contrast, immature animals are capable to heal defects of identical size. It was our hypothesis that age-related paracrine effects are relevant for this difference in regeneration.', 'The pooled supernatant of primary rat calvarial osteoblast-like cell cultures (POBC) derived from prenatal or postnatal donors was concentrated and applied into CSDs of adult recipient organisms (n = 10). In addition, the supernatant of POBC derived from prenatal donors was pooled and purified by reverse-phase chromatography. Each pre-purified fraction was tested in a proliferation indicating bioassay. Peptide fractions containing proliferative activities were re-chromatographed and re-tested in a bioassay. Finally, a proliferative activity was purified, identified by sequence analysis and applied into CSDs of adult recipients.', 'The application of POBC derived from prenatal donors resulted in osseous regeneration of a CSD in adult recipients, while the supernatant of postnatal donors had much smaller effects. The morphologic features resembled the spontaneous osseous healing of calvarial defects of the same size in immature organisms. The polypeptide \"tissue inhibitor of metalloproteinases type II\"(TIMP-2) was isolated from the supernatant of cultures of POBC derived from prenatal donors by measuring the induction of their proliferation. Additionally, the application of human TIMP-2 injected into calvarial CSDs of adult organisms resulted in osseous healing.",
            "output": [
                "Is tissue inhibitor of metalloproteinases II ( TIMP-2 ) an osteoanabolic factor in vitro and in vivo?"
            ]
        },
        {
            "id": "task847-8a67239fc7114541b0b4d6ac3477e0e5",
            "input": "Deficiency of the antiprotease alpha-1-antitrypsin (AAT) and exposure to cigarette smoke (CS) contribute to the development of early onset emphysema. CS-induced apoptosis of alveolar cells including endothelial cells plays critical role in the lung destruction. AAT deficiency is associated with increased lung tissue destruction as well. We hypothesize that AAT protects lung alveoli from noxious environmental stimuli such as CS-induced apoptosis.', 'Porcine pulmonary artery endothelial cells (PAEC) were exposed to CS in the presence or absence of AAT (20 microM). AAT internalization and markers for apoptosis were assessed by confocal microscopy. Flow cytometry was performed in parallel to quantify the number of AAT-loaded and apoptotic cells.', 'We demonstrated that exogenous AAT accumulated in PAEC and protected cells from CS-induced apoptosis. AAT-loaded CS-exposed cells exhibited increased amounts of chaperone HSP-70 in their cytosol and less apoptosis inducing factor in their nuclei compared to AAT-untreated, CS-exposed cells.",
            "output": [
                "Does endothelial alpha-1-antitrypsin attenuate cigarette smoke induced apoptosis in vitro?"
            ]
        },
        {
            "id": "task847-bc33b15ab8ca4fbcb1af33c6f3d155ce",
            "input": "The objective was to compare implants in the posterior maxilla with or without sinus floor augmentation.', 'A retrospective study was conducted of patients who received implants in the posterior maxilla. All patients received solitary, implant-retained fixed partial dentures or crowns. A standardized form for implant treatment was used to document the follow-up examination. The different parameters were initially analyzed descriptively by frequency distribution, measure of central tendency, and statistical spread. A 95% level of significance was set for all tests.', 'A total of 76 patients with 141 dental implants in the posterior region of the maxilla were evaluated. Fifty-one patients with 71 implants received prior no augmentation (sinus floor elevation) and composed the control group. Twenty-five patients with 70 implants received an additional bone transfer prior to implant placement. The mean age of the patients at time of the follow-up examination was 49.7 years in the overall group, 52.6 years for men and 46.7 years for women. The implants inserted in an augmented area had similar implant stability and implant loss results after a mean functional observation period of 1.6 years (range, 0.5 to 4.7 years) compared to those inserted without augmentation. Augmented implants exhibited less peri-implant bone resorption.",
            "output": [
                "Do comparative clinical results after implant placement in the posterior maxilla with and without sinus augmentation?"
            ]
        },
        {
            "id": "task847-d938116606c9402489ecb01f8657cdea",
            "input": "Psychostimulants are often used in close temporal proximity to nicotine and have been reported to enhance acutely nicotine's desirability in humans.\", 'To investigate the acute associations between amphetamine and nicotine, we examined the potentiative interactions between clinically relevant, low doses of these drugs on locomotor activity, and dopamine overflow in the rat.', 'Locomotor activity was measured by telemetry in the home cage environment, and dopamine overflow was evaluated in striatal slice preparations from female Holtzman rats.', 'When administered simultaneously, nicotine and amphetamine produced a predominantly additive effect on locomotor behavior. However amphetamine, when given 2-4 h before nicotine, strongly potentiated nicotine-induced locomotor activity. Correspondingly, nicotine given 1-4 h before amphetamine robustly enhanced amphetamine-stimulated locomotor activity even when the effects of the nicotine pretreatment dissipated. Acute nicotine pretreatment similarly potentiated the effects of dopamine transporter ligands, cocaine, nomifensine, and methamphetamine but not a direct dopamine receptor agonist. Consistent with the behavioral studies, in vivo nicotine pretreatment exaggerated amphetamine-induced dopamine efflux from rat striatal slices. Likewise, in vivo pretreatment of rats with amphetamine potentiated nicotine-induced dopamine efflux from striatal slices. Direct pretreatment of striatal tissue by nicotine also potentiated subsequent amphetamine-stimulated dopamine overflow, further suggesting that the nicotine-amphetamine interaction occurs at the level of the dopamine terminal.",
            "output": [
                "Do nicotine and amphetamine acutely cross-potentiate their behavioral and neurochemical responses in female Holtzman rats?"
            ]
        },
        {
            "id": "task847-cf8e1b060db749d48215b50f98e7a0e5",
            "input": "The generation of inflammatory mediators from monocytes activated by HLA Class II antibodies is thought to play important roles in the etiology of nonhemolytic transfusion reactions. Increased permeability of endothelial cells contributes to the pathogenesis of rash, urticaria, angioedema, and pulmonary edema, which are symptoms of transfusion reactions.', 'We investigated whether inflammatory mediators released from monocytes upon stimulation by HLA Class II antibodies could increase endothelial permeability. Human endothelial cell monolayers were incubated with cell-free supernatants of peripheral blood mononuclear cells (PBMNCs) stimulated with HLA Class II antibody-containing plasma (anti-HLA-DR plasma), which has been implicated in severe nonhemolytic transfusion reactions. The permeability of endothelial cells to dextran was measured.', 'The supernatants of PBMNCs stimulated with the anti-HLA-DR plasma in corresponding antigen-antibody combinations were able to increase endothelial permeability. At least 3 hours of exposure of PBMNCs to anti-HLA-DR plasma was required to produce a supernatant that could induce a significant increase in permeability. Simultaneous addition of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) neutralizing antibodies to the activated PBMNC supernatant significantly reduced the increase in permeability. Treatment of the endothelial cells with an inhibitor of nuclear factor kappaB (NF-kappaB), but not inhibitors of apoptosis, significantly prevented the increase in permeability.",
            "output": [
                "Is endothelial permeability increased by the supernatant of peripheral blood mononuclear cells stimulated with HLA Class II antibody?"
            ]
        },
        {
            "id": "task847-dc68656268b54005bfdd84f11eb4ee9f",
            "input": "Ginkgo biloba extract, EGb761, is one of the most commonly used herbal supplements throughout Western society. It has been used in the treatment of various common geriatric complaints including short-term memory loss. We showed that acute systemic administration of EGb761 enhanced fear-potentiated startle (FPS) in rats. Little is known about the behavioral effects of centrally administered EGb761 on FPS.', 'The current study was performed to evaluate the involvement of basolateral nucleus of amygdala (BLA) in the EGb761 facilitation effect on FPS.', \"Male adult SD rats were used. EGb761 was infused into cerebroventricle or basolateral nucleus of amygdala 10 min prior to fear conditioning. Animals were then tested for FPS 24 h later. Results showed that (1) intra-cerebroventricular infusion of EGb761 (0.1, 1.0, or 3.0 microg/3.0 microl per side, bilaterally) and intra-amygdaloid infusion of EGb761 (1.0, 14.0, or 28.0 ng/microl per side, bilaterally) 30 and 10 min prior to fear conditioning, respectively, facilitated FPS in a dose-dependent manner. (2) Administration of EGb761 did not impair an animal's basal startle response or pain perception. (3) Subsequent control experiment's results indicated that the facilitation effect of EGb761 on the acquisition was not due to anxiogenic effect or non-specific effect.",
            "output": [
                "Does intra-amygdaloid infusion of Ginkgo biloba leaf extract ( EGb761 ) facilitate fear-potentiated startle in rats?"
            ]
        },
        {
            "id": "task847-9f3116de86a74a0db1223aacfbf542db",
            "input": "In dialysis patients, volume overhydration is common and is related to increased risk of cardiovascular morbidity and mortality. However, it remains unclear whether volume overload imposes those detrimental effects through endothelial dysfunction.', 'In this cross-sectional study, 81 stable patients on continuous ambulatory peritoneal dialysis in a single center were recruited. Volume status was evaluated by extracellular water, assessed by bioimpedance analysis, and normalized to individual height (nECW). Endothelial function was estimated by endothelial-dependent flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter.', 'There were 37 male and 44 female patients (mean age 61 +/- 12 years, dialysis vintage 20 +/- 23 months). FMD in female patients was significantly higher than that in male patients (9.17% +/- 6.23% vs 6.31% +/- 5.01%, p < 0.05). FMD was negatively correlated with weight (r = -0.308, p < 0.01), body mass index (r = -0.242, p < 0.05), systolic blood pressure (r = -0.228, p < 0.05), ECW (r = -0.404, p < 0.001), and nECW (r = -0.418, p < 0.001). No correlation was found between FMD and other variables. In multiple stepwise regression analysis, calcium x phosphate product (beta = 0.422, p < 0.001), nECW (beta = -0.343, p < 0.01), and dialysis vintage (beta = -0.237, p < 0.05) were independent determinants of FMD (adjusted R(2) = 0.327 for this model).",
            "output": [
                "Is volume overhydration related to endothelial dysfunction in continuous ambulatory peritoneal dialysis patients?"
            ]
        },
        {
            "id": "task847-518ebce2e2dc4ecbab5348cd8f907000",
            "input": "Granulocyte-colony stimulating factor (G-CSF) is used for the mobilization of bone marrow and endothelial progenitor cells, though G-CSF-induced inflammation may cause endothelial dysfunction. We examined the effects of G-CSF on endothelium, C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha) and anti-inflammatory cytokines namely interleukin 10 (IL-10).', 'We studied 60 women with breast cancer, who were randomized to either subcutaneous G-CSF (5 microg/kg), o.d. for 5 days after adjuvant chemotherapy (n = 40) or placebo (n = 20).', 'We measured flow-mediated dilatation (FMD%) of the brachial artery by ultrasonography, CRP, TNF-alpha, IL-10 and the ratio TNF-alpha/ IL-10 blood levels before, 2-h and 5-days after the G-CSF or placebo treatment.', 'There was a greater increase of FMD, IL-10 and reduction of TNF-alpha/ IL-10, 2 h and 5 days after the G-CSF treatment compared to placebo. Although, CRP and TNF-alpha were higher, TNF-alpha/IL-10 was lower at the end of G-CSF treatment compared to placebo. Improvement of FMD was related to changes of IL-10 and TNF-alpha/IL-10.",
            "output": [
                "Is treatment with granulocyte colony stimulating factor associated with improvement in endothelial function?"
            ]
        },
        {
            "id": "task847-6c61e3f86a234947aa11986beec0265d",
            "input": "Group B Streptococcus (GBS) is a leading cause of neonatal sepsis where myocardial dysfunction is an important contributor to poor outcome. Here we study the effects of the GBS pore-forming beta-hemolysin/cytolysin (Bh/c) exotoxin on cardiomyocyte viability, contractility, and calcium transients.', 'HL-1 cardiomyocytes exposed to intact wild-type (WT) or isogenic Deltabeta h/c mutant GBS, or to cell-free extracts from either strain, were assessed for viability by trypan blue exclusion and for apoptosis by TUNEL staining. Functionality of exposed cardiomyocytes was analyzed by visual quantitation of the rate and extent of contractility. Mitochondrial membrane polarization was measured in TMRE-loaded cells exposed to GBS beta h/c. Effects of GBS beta h/c on calcium transients were studied in fura-2AM-loaded primary rat ventricular cardiomyocytes. Exposure of HL-1 cardiomyocytes to either WT GBS or beta h/c extracts significantly reduced both rate and extent of contractility and later induced necrotic and apoptotic cell death. No effects on cardiomyocyte viability or function were observed after treatment with Deltabeta h/c mutant bacteria or extracts. The beta h/c toxin was associated with complete and rapid loss of detectable calcium transients in primary neonatal rat ventricular cardiomyocytes and induced a loss of mitochondrial membrane polarization. These effects on viability and function were abrogated by the beta h/c inhibitor, dipalmitoyl phosphatidylcholine (DPPC).",
            "output": [
                "Does group B streptococcal beta-hemolysin/cytolysin directly impair cardiomyocyte viability and function?"
            ]
        },
        {
            "id": "task847-26b98788883b479a81bd3b118de90bf4",
            "input": "Elucidation of the repertoire of secreted and cell surface proteins of tumor cells is relevant to molecular diagnostics, tumor imaging and targeted therapies. We have characterized the cell surface proteome and the proteins released into the extra-cellular milieu of three ovarian cancer cell lines, CaOV3, OVCAR3 and ES2 and of ovarian tumor cells enriched from ascites fluid.', 'To differentiate proteins released into the media from protein constituents of media utilized for culture, cells were grown in the presence of [(13)C]-labeled lysine. A biotinylation-based approach was used to capture cell surface associated proteins. Our general experimental strategy consisted of fractionation of proteins from individual compartments followed by proteolytic digestion and LC-MS/MS analysis. In total, some 6,400 proteins were identified with high confidence across all specimens and fractions.",
            "output": [
                "Does proteomic analysis of ovarian cancer cells reveal dynamic processes of protein secretion and shedding of extra-cellular domains?"
            ]
        },
        {
            "id": "task847-382a9b8319e94d9c9043d0fcc2ad5925",
            "input": "Expression of truncated G-CSFR forms in patients with SCN/AML induces hyperproliferation and prolonged cell survival. Previously, we showed that ligand internalization is delayed and degradation of truncated G-CSFR forms is defective in patients with SCN/AML.', 'In this study, we investigated the potential roles of dileucine and tyrosine-based motifs within the cytoplasmic domain of the G-CSFR in modulating ligand/receptor internalization. Using standard binding assays with radiolabeled ligand and COS-7 cells, substitutions in the dileucine motif or deletion of tyrosine residues in the G-CSFR did not alter internalization. Attachment of the transferrin receptor YTRF internalization motif to a truncated G-CSFR form from a patient with SCN/AML corrected defective internalization, but not receptor degradation suggesting that receptor internalization and degradation occur independently via distinct domains and/or processes.",
            "output": [
                "Do divergent pathways in COS-7 cells mediate defective internalization and intracellular routing of truncated G-CSFR forms in SCN/AML?"
            ]
        },
        {
            "id": "task847-7e0fb8c0a9f74a2db49d329a93ee722e",
            "input": "Studying axonal loss in the retina is a promising biomarker for multiple sclerosis (MS). Our aim was to compare optical coherence tomography (OCT) and Heidelberg retinal tomography (HRT) techniques to measure the thickness of the retinal nerve fiber layer (RNFL) in patients with MS, and to explore the relationship between changes in the RNFL thickness with physical and cognitive disability. We studied 52 patients with MS and 18 proportionally matched controls by performing neurological examination, neuropsychological evaluation using the Brief Repetitive Battery-Neuropsychology and RNFL thickness measurement using OCT and HRT.', 'We found that both OCT and HRT could define a reduction in the thickness of the RNFL in patients with MS compared with controls, although both measurements were weakly correlated, suggesting that they might measure different aspects of the tissue changes in MS. The degree of RNFL atrophy was correlated with cognitive disability, mainly with the symbol digit modality test (r=0.754, P<0.001). Moreover, temporal quadrant RNFL atrophy measured with OCT was associated with physical disability.",
            "output": [
                "Is retinal nerve fiber layer atrophy associated with physical and cognitive disability in multiple sclerosis?"
            ]
        },
        {
            "id": "task847-efef834aadfb493499fa8eec986ac953",
            "input": "Inflammation and reactive oxygen species (ROS) are important in the development of perinatal brain injury. The ROS-generating enzyme NADPH oxidase (Nox2) is present in inflammatory cells and contributes to brain injury in adult animal models.', 'NADPH oxidase contributes to ROS formation and development of injury in the immature brain and inhibition of NADPH oxidase attenuates perinatal brain injury.', 'We used animal models of term hypoxia-ischemia (HI) (P9 mice) as well as ibotenate-induced excitotoxic injury (P5 mice) mimicking features of periventricular leukomalacia in preterm infants. In vitro microglia cell cultures were used to investigate NADPH oxidase-dependent ROS formation. In vivo we determined the impact 1) of HI on NADPH oxidase gene expression 2) of genetic (gp91-phox/Nox2 knock-out) and 3) of pharmacological NADPH oxidase inhibition on HI-induced injury and NMDA receptor-mediated excitotoxic injury, respectively. Endpoints were ROS formation, oxidative stress, apoptosis, inflammation and extent of injury.', 'Hypoxia-ischemia increased NADPH oxidase subunits mRNA expression in total brain tissue in vivo. In vitro ibotenate increased NADPH oxidase-dependent formation of reactive oxygen species in microglia. In vivo the inhibition of NADPH oxidase did not reduce the extent of brain injury in any of the animal models. In contrast, the injury was increased by inhibition of NADPH oxidase and genetic inhibition was associated with an increased level of galectin-3 and IL-1beta.",
            "output": [
                "Does pharmacological and genetic inhibition of NADPH oxidase reduce brain damage in different models of perinatal brain injury in newborn mice?"
            ]
        },
        {
            "id": "task847-eb966b1dd76f47dab693de923bd51a96",
            "input": "Human prion protein gene (PRNP) is considered a critical and fundamental gene in determining the incidence of human prion diseases. Codons 129 and 219 play an important role in the susceptibility to sporadic Creutzfeldt-Jakob disease (CJD). An association between sporadic CJD and the polymorphism (PRNP 1368) in an upstream of PRNP exon 1 has been reported in the British and German populations, but study in the Dutch population has failed to confirm an association.', 'To investigate whether the PRNP 1368 polymorphism is associated with sporadic CJD in the Korean population.', 'We compared the genotype and allele frequencies of PRNP 1368 polymorphism in 171 sporadic CJD patients with those in 212 healthy Koreans.",
            "output": [
                "Is pRNP 1368 polymorphism associated with sporadic Creutzfeldt-Jakob disease in the Korean population?"
            ]
        },
        {
            "id": "task847-51c1c0998f4b4e64abc7397b70c49ba1",
            "input": "Prion protein (PrP) predominantly localized at synapses can modulate neuronal excitability. The prion protein gene (PRNP) has been considered one of the candidate genes that play a role in seizure susceptibility. A recent study demonstrated that the 129V allele in the PRNP gene was associated with susceptibility to temporal lobe epilepsy (TLE) in female patients in an Italian population. We screened variations in the open-reading frame (ORF) of the PRNP gene and also replicated the association of the M129V polymorphism with TLE in a Han Chinese population.', 'The M129V polymorphism was genotyped in 320 MTLE patients and 558 non-epilepsy controls. All subjects were Han Chinese.', 'No novel polymorphism in the ORF of the PRNP gene was detected. Differences in the genotype distributions and allele frequencies of this polymorphism between cases and controls were insignificant (P = 0.24). Further analysis with stratification of the results by gender or age and analysis of clinical features in relation to M129V genotypes also yielded negative findings.",
            "output": [
                "Is m129V polymorphism in the prion protein gene associated with mesial temporal lobe epilepsy in a Han Chinese population?"
            ]
        },
        {
            "id": "task847-0a5f5dd2d41a434696558f472d57e238",
            "input": "Nonasthmatic eosinophilic bronchitis (EB) has emerged as a useful tool to study the structural and inflammatory mechanisms of airway hyperresponsiveness (AHR) in asthma. We have previously shown that vascular remodeling and reticular basement membrane (RBM) thickening are present in EB. However, it is not known whether other features of structural remodeling including increased airway smooth muscle (ASM) mass, matrix deposition, and glandular hyperplasia are also present in EB.', 'We sought to determine whether structural remodeling occurs in EB and is associated with AHR and airflow limitation.', 'Forty-two patients with asthma, 21 patients with EB, and 19 healthy volunteers were recruited. ASM area, RBM thickness, collagen 3 deposition, glandular area, mast cells, and granulocytes were assessed in bronchial biopsy samples.', 'Nonasthmatic eosinophilic bronchitis and asthma were associated with a significant increase in ASM mass and RBM thickness compared with healthy subjects. In contrast, we did not observe any significant differences in collagen 3 deposition in the lamina propria and ASM or the % area of glands in the lamina propria. Univariate analysis demonstrated that mast cell numbers in the ASM were the only feature of remodeling associated with AHR (beta = -0.51; P = .004). Stepwise linear regression revealed that a combination of mast cell numbers in the ASM (beta = -0.43) and disease duration (beta = -0.25; model-adjusted R(2) = 0.26; P = .027) best modeled AHR.",
            "output": [
                "Is airway hyperresponsiveness dissociated from airway wall structural remodeling?"
            ]
        },
        {
            "id": "task847-72c916dfa8f5433fb205607266f1b148",
            "input": "Contact of blood with artificial surfaces and air as well as ischemia/reperfusion injury to the heart and lungs mediate systemic and local inflammation during cardiopulmonary bypass (CPB). Activation of complement and coagulation cascades leads to and accompanies endothelial cell damage. Therefore, endothelial-targeted cytoprotection with the complement inhibitor and endothelial protectant dextran sulfate (DXS, MW 5000) may attenuate CBP-associated myocardial and pulmonary injury.', 'Eighteen pigs (DXS, n=10; phosphate buffered saline [PBS], n=8) underwent standard cardiopulmonary bypass. After aortic cross-clamping, cardiac arrest was initiated with modified Buckberg blood cardioplegia (BCP), repeated after 30 and 60 min with BCP containing either DXS (300 mg/10 ml, equivalent to 5mg/kg) or 10 ml of PBS. Following 30 min reperfusion, pigs were weaned from CPB. During 2h of observation, cardiac function was monitored by echocardiography and invasive pressure measurements. Inflammatory and coagulation markers were assessed regularly. Animals were then sacrificed and heart and lungs analyzed.', 'DXS significantly reduced CK-MB levels (43.4+/-14.8 ng/ml PBS, 35.9+/-11.1 ng/ml DXS, p=0.042) and significantly diminished cytokine release: TNFalpha (1507.6+/-269.2 pg/ml PBS, 222.1+/-125.6 pg/ml DXS, p=0.0071), IL1beta (1081.8+/-203.0 pg/ml PBS, 110.7+/-79.4 pg/ml DXS, p=0.0071), IL-6 (173.0+/-91.5 pg/ml PBS, 40.8+/-19.4 pg/ml DXS, p=0.002) and IL-8 (304.6+/-81.3 pg/ml PBS, 25.4+/-14.2 pg/ml DXS, p=0.0071). Tissue endothelin-1 levels were significantly reduced (6.29+/-1.90 pg/100mg PBS, 3.55+/-1.15 pg/100mg DXS p=0.030) as well as thrombin-anti-thrombin formation (20.7+/-1.0 microg/ml PBS, 12.8+/-4.1 microg/ml DXS, p=0.043). Also DXS reduced cardiac and pulmonary complement deposition, neutrophil infiltration, hemorrhage and pulmonary edema (measured as lung water content, 81+/-3% vs 78+/-3%, p=0.047), indicative of attenuated myocardial and pulmonary CPB-injury. Diastolic left ventricular function (measured as dp/dt(min)), pulmonary artery pressure (21+/-3 mmHg PBS, 19+/-3 mmHg DXS, p=0.002) and right ventricular pressure (21+/-1 mmHg PBS, 19+/-3 mmHg DXS p=0.021) were significantly improved with the use of DXS.",
            "output": [
                "Does addition of dextran sulfate to blood cardioplegia attenuate reperfusion injury in a porcine model of cardiopulmonary bypass?"
            ]
        },
        {
            "id": "task847-452f15c2011a4ce8aeaaef43ce8e8572",
            "input": "Exercise tests are increasingly used during preoperative evaluation before lung resection. This study assessed the association between performance at the symptom-limited stair-climbing test and postoperative cardiopulmonary morbidity, mortality, and costs after major lung resections.', 'As part of their routine preoperative evaluation, 640 patients who had lobectomy (n = 533) or pneumonectomy (n = 107) for lung cancer from January 2000 through April 2007 performed a preoperative symptom-limited stair-climbing test. Sensitivity/specificity analysis was used to identify the best cutoff values of altitude climbed (number of steps x height of the step in m) associated with outcome. Univariate and multivariate regression analyses (validated by bootstrap) were used to test associations between preoperative and operative factors and postoperative cardiopulmonary complications, mortality, and postoperative costs.', 'The altitude reached at the stair-climbing test was reliably associated with increased cardiopulmonary complications (p = 0.04), mortality (p = 0.02), and costs (p < 0.0001). In patients who climbed less than 12 m, cardiopulmonary complications, mortality, and costs were 2-fold (p < 0.0001), 13-fold (p < 0.0001), and 2.5-fold higher, respectively, than in patients who climbed more than 22 m.",
            "output": [
                "Is performance at symptom-limited stair-climbing test associated with increased cardiopulmonary complications , mortality , and costs after major lung resection?"
            ]
        },
        {
            "id": "task847-f28d102046b149fab4edd4ef1eee0f84",
            "input": "In RA, conflicting results have been described on the association between genotypes of the complement factor mannose-binding lectin (MBL) and disease susceptibility and severity. This might be due to underpowerment of previous research work and the fact that no confirmation cohorts were used. Therefore a different approach is warranted.', 'MBL2 gene polymorphisms were determined in two RA cohorts (378 and 261 cases) and 648 controls. Considering MBL polymorphisms, cases and controls were categorized in groups of high, intermediate and low MBL production. The total sample size allows detection of a potential association between RA susceptibility and MBL groups with an odds ratio of 1.37 (alpha < 0.05; 1-beta > 0.8). Disease severity as defined by the need for anti-TNF therapy was also analysed for possible associations with MBL groups.', 'There was no difference in the frequencies between MBL genotypes of RA cases and controls that are associated with high (cases 54.4%, controls 57.0%), intermediate (cases 28.9%, controls 27.5%) or low (cases 16.7%, controls 15.5%) MBL production. Furthermore, there was no association between MBL groups and disease severity.",
            "output": [
                "Are mannose-binding lectin polymorphisms associated with rheumatoid arthritis -- confirmation in two large cohorts?"
            ]
        },
        {
            "id": "task847-9eac082eb17343eaa81b20441f2a122a",
            "input": "Recurrent loss of part of the long arm of chromosome 11 is a well established hallmark of a subtype of aggressive neuroblastomas. Despite intensive mapping efforts to localize the culprit 11q tumour suppressor gene, this search has been unsuccessful thus far as no sufficiently small critical region could be delineated for selection of candidate genes.', \"To refine the critical region of 11q loss, the chromosome 11 status of 100 primary neuroblastoma tumours and 29 cell lines was analyzed using a BAC array containing a chromosome 11 tiling path. For the genes mapping within our refined region of loss, meta-analysis on published neuroblastoma mRNA gene expression datasets was performed for candidate gene selection. The DNA methylation status of the resulting candidate gene was determined using re-expression experiments by treatment of neuroblastoma cells with the demethylating agent 5-aza-2'-deoxycytidine and bisulphite sequencing.\", 'Two small critical regions of loss within 11q23 at chromosomal band 11q23.1-q23.2 (1.79 Mb) and 11q23.2-q23.3 (3.72 Mb) were identified. In a first step towards further selection of candidate neuroblastoma tumour suppressor genes, we performed a meta-analysis on published expression profiles of 692 neuroblastoma tumours. Integration of the resulting candidate gene list with expression data of neuroblastoma progenitor cells pinpointed CADM1 as a compelling candidate gene. Meta-analysis indicated that CADM1 expression has prognostic significance and differential expression for the gene was noted in unfavourable neuroblastoma versus normal neuroblasts. Methylation analysis provided no evidence for a two-hit mechanism in 11q deleted cell lines.",
            "output": [
                "Is cADM1 a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23?"
            ]
        },
        {
            "id": "task847-817a458d1d164a4893b1123ed7780dae",
            "input": "To explore the influence of buried penis on nitric oxide synthase (NOS) activity of the corpus cavernosum in rats.', 'The experimental model of concealed penis was established by intra-pocket-suture of the root of the penis. Two hundred and forty rats were equally randomized into a 2, a 4 and a 6 months group, each further divided into a buried (n = 50), a sham operation (n = 15) and a normal subgroup (n = 15). The development of the corpus cavernosum was surveyed by measuring its weight and the ratio to the body weight, followed by determination of NOS activity in the corpus cavernosum by spectrophotometry.', 'No significant differences were found in the corpus cavernosum weight, the body weight and their ratio among the buried, sham operation and normal groups in any experimental stage (P > 0.05). Buried penis decreased NOS activity in the 4- and 6-month groups (P < 0.05 and P < 0.01) compared with the normal group, but effected no significant change in the 2-month group.",
            "output": [
                "Does [ Buried penis decrease nitric oxide synthase of the corpus cavernosum ]?"
            ]
        },
        {
            "id": "task847-1063bd12207540f2a2501bdfcc0f5b31",
            "input": "To explore the effect of subchronic exposure to acrylamide on the reproduction and testis endocrine function of rats.', 'Forty healthy adult male SD rats were randomly divided into 4 groups of equal number, exposed to acrylamide at the dose of 0, 4, 10 and 18 mg/(kg x d) respectively for 9 weeks, and then subjected to the determination of the hindlimb landing foot splay, sperm vitality and morphology, the activities of acid phosphatase (ACP) and alkaline phosphatase (ALP) in the testis homogenate, and the levels of testosterone (T) and estradiol (E2) in the serum and testis homogenate. Based on the primary Leydig cell culture models exposed to acrylamide of 0, 0.1, 0.75, 4 and 8 mmol/L, the activity of Leydig cells was measured by the CCK-8 method.', 'Following acrylamide exposure, the hindlimb landing foot splay increased markedly with dose increase (P < 0.01). The rates of sperm vitality were (6.86 +/- 5.46)%, (65.43 +/- 5.16)%, (60.86 +/- 4.26)% and (46.86 +/- 2.73)% in the exposed groups, significantly lower than in the control (P < 0.01); the rates of abnormal sperm were (39.00 +/- 10.95)%, (35.43 +/- 7.54)%, (45.71 +/- 13.28)% and (56.71 +/- 17.01)%, significantly increased in the 10 and 18 mg/(kg x d) groups (P < 0.05); ACP activities were (82.93 +/- 11.05), (73.52 +/- 8.77), (77.67 +/- 3.04) and (68.56 +/- 3.09) U/g prot, showing a decreasing tendency, while ALP activities were (0.96 +/- 0.15), (1.07 +/- 0.22), (1.12 +/- 0.22) and (0.74 +/- 0.10) U/g prot, displaying a tendency of first increasing and then decreasing. Both ACP and ALP activities were inhibited significantly in the 18 mg/(kg x d) group as compared with the control (P < 0.05). A marked reduction was noted in T levels in the serum, (13.44 +/- 4.76), (7.69 +/- 3.84), (5.23 +/- 1.42) and (1.36 +/- 0.86) ng/ml, as well as in the testis homogenate, (4.95 +/- 1.64), (3.01 +/- 0.76), (2.44 +/- 0.91) and (0.85 +/- 0.49) ng/mg prot, (P < 0.01), but no significant changes were observed in 17beta-E2 levels. After 24 hours exposure to acrylamide, the optical densities were 0.82 +/- 0.06, 0.56 +/- 0.07, 0.44 +/- 0.06, 0.26 +/- 0.03 and 0.45 +/- 0.21, showing an evident inhibition of the activity of Leydig cells at the dose of 0.1, 0.75, 4 and 8 mmol/L (P < 0.01).",
            "output": [
                "Does [ Subchronic exposure to acrylamide affect reproduction and testis endocrine function of rats ]?"
            ]
        },
        {
            "id": "task847-e381029258c043f8adad38fd54706b14",
            "input": "To explore the protective effect of the Phyllanthus Urinaria (PU) extract on the N-cadherin expression in the testicular tissues disrupted by nitrogen mustard (HN2) in vivo.', 'HN2 was intraperitoneally injected into male KM mice at the dose of 5 mg/kg to make reproductive toxicity models, and at the same time PU was administered for intervention at the dose of 125 mg/kg, 250 mg/kg and 500 mg/kg. N-cadherin distribution, mRNA and protein expression in the testicular tissues were detected by immunohistochemistry, RT-PCR and Western blotting.', 'N-cadherin was mainly distributed in the membrane and cytoplasm of Sertoli cells at the basement of seminiferous epithelia, Leydig cells and peritubular cells, scarcely expressed in the basement of seminiferous epithelia and peritubular cells after HN2 administration. The expressions of mRNA and proteins of N-cadherin were significantly elevated with the increased dose of PU (P < 0.01). Compared with the normal control, the distribution and expression of N-cadherin showed no significant differences in either the high-dose PU group or the HN2 with high-dose PU intervention group (P > 0.05).",
            "output": [
                "Does [ Phyllanthus urinaria extract promote N-cadherin expression in nitrogen mustard-disrupted testicular tissues in vivo ]?"
            ]
        },
        {
            "id": "task847-ef123172605d44f1827bfcd8edc5a636",
            "input": "To evaluate the applicability of the WHO densitometric criteria for the diagnosis of spinal osteoporosis in men and to compare it with women with vertebral fractures, as well as to analyze the role of vertebral dimensions in the development of spinal fractures.', 'For these purposes we analyzed, using DXA, vertebral projected area and lumbar bone mineral density (BMD), as well as T and Z-scores in lumbar spine in a cohort of 66946 individuals; 2556 of these subjects had one or more atraumatic vertebral fracture (396 men and 2160 postmenopausal women).', 'Men and women with fractures showed significantly lower mean BMD, T-score and Z-score values than individuals without fractures while vertebral dimensions were similar in both groups of patients. When comparing men and women with vertebral fractures, the former showed a significantly greater projected area (46.89+/-5.5 vs. 39.13+/-4.6 cm(2) p<0.001) and lumbar BMD (0.991+/- 0.21 vs. 0.938+/- t0.19 g/cm(2) p<0.001). However, the median lumbar T-score values were similar for both sexes (-2.3 in women vs. -2.2 in men; p: NS). In addition, a similar percentage of men and women with vertebral fractures showed T-score values <-2.5 in the lumbar spine (44% vs. 46%, p=NS).",
            "output": [
                "Do men suffer vertebral fractures with similar spinal T-scores to women?"
            ]
        },
        {
            "id": "task847-bd14e97e34014ddca993cd8f9f904697",
            "input": "This study investigated whether deletion of the alpha1A-adrenoceptor gene influences contractile responses of mouse prostate to noradrenaline. Responses of mouse prostate to noradrenaline are known to be mediated by alpha1L-adrenoceptors, which are thought to be a functional phenotype of alpha1A-adrenoceptor.', 'Prostate tissues from alpha1A-adrenoceptor knockout mice which were homozygous (alpha1A -/-) and heterozygous (alpha1A +/-) for the disrupted alpha1A-adrenoceptor gene, as well as wild-type (alpha1A +/+) littermates were mounted in glass-isolated organ baths. Electrical field stimulation of nerves and exogenous application of noradrenaline were used to investigate the effects of alpha1A-adrenoceptor disruption on prostate contractility.', 'Frequency-response curves to electrical field stimulation (0.5 ms pulse duration, 60 V, 0.1-20 Hz) yielded frequency-dependent contractions. At frequencies of 10 and 20 Hz, prostates from alpha1A -/- mice elicited an approximately 30% decreased response compared with prostates from alpha(1A)+/+ mice. Prazosin (0.3 muM) attenuated responses to electrical field stimulation in prostates from alpha1A +/+ and alpha1A +/- mice but not from alpha1A -/- mice. Increasing concentrations of exogenously administered noradrenaline (10 nM-1 mM) produced mean concentration-response curves in prostates from alpha1A +/+ and alpha1A +/- mice, which were not different. Maximum responses to noradrenaline were decreased by approximately 80% in prostates from alpha1A -/- mice compared with alpha1A +/+ mice. Prazosin attenuated responses to noradrenaline in all genotypes.",
            "output": [
                "Is the alpha1A-adrenoceptor gene required for the alpha1L-adrenoceptor-mediated response in isolated preparations of the mouse prostate?"
            ]
        },
        {
            "id": "task847-21987146e54b473a8f434ca15fd5e161",
            "input": "We recently proposed the existence of neurotoxic interactions between the cannabinoid type 1 (CB(1)) receptor and transient receptor potential vanilloid 1 (TRPV1) channels in rat mesencephalic cultures. This study seeks evidence for the mediator(s) and mechanisms underlying the neurotoxic interactions between CB(1) receptors and TRPV1 in vitro and in vivo.', 'The mediator(s) and mechanism(s) for the interactions between CB(1) receptors and TRPV1 were evaluated by cell viability assays, immunocytochemistry, Fura-2 calcium imaging, mitochondrial morphology assay, ELISA and Western blot assay in vitro in neuron-enriched mesencephalic cultures. Injections into the substantia nigra and subsequent cell counts were also used to confirm these interactions in vivo.', 'The neurotoxic interactions were mediated by 12(S)-hydroperoxyeicosatetraenoic acid (12(S)-HPETE), an endogenous TRPV1 agonist. CB(1) receptor agonists (HU210 and WIN55,212-2) increased the level of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a downstream metabolite of 12(S)-HPETE, which stimulates TRPV1-mediated death of mesencephalic neurons, both in vitro and in vivo. The neurotoxicity was mediated by increased intracellular Ca(2+) concentration ([Ca(2+)](i)) through TRPV1, consequently leading to mitochondrial damage and was attenuated by baicalein, a 12-lipoxygenase inhibitor.",
            "output": [
                "Are interactions between CB ( 1 ) receptors and TRPV1 channels mediated by 12-HPETE cytotoxic to mesencephalic dopaminergic neurons?"
            ]
        },
        {
            "id": "task847-816e537298a24f1e86deed29e277b6f1",
            "input": "To study the role of peroperative transrectal ultrasonography (peTRUS) for the dissection of the bladder neck during robot-assisted laparoscopic prostatectomy (RALP).', 'Integrated peTRUS in the da Vinci S system (Intuitive Surgical, Sunnyvale, CA, USA) was used for bladder neck identification and dissection in the initial 80 patients with clinically localized prostate cancer operated by two urologists. The clinical and pathological results were compared with the initial 80 patients who had RALP with no peTRUS. The location of positive margins was recorded.', \"The operative duration, blood loss, hospital stay, catheter dependency, clinical and pathological T-stage and Gleason sum score were no different between the groups. The prostate-specific antigen level at time of diagnosis was slightly higher for patients in the peTRUS group. Basal surgical margins (bladder neck and basal areas of both prostate lobes) were positive for tumour in 9.1% and 2.3% of patients treated without and with peTRUS, respectively (P = 0.001). Although the use of peTRUS improved the basal margin rate in the initial 30 patients in each group, it did not in the last 30 in each group, when the urologist's experience apparently improved. In a multivariate analysis the use of peTRUS and pathological T-stage were the best predictors of basal margin status. Pad use at 6 months after surgery was similar for both groups.",
            "output": [
                "Does peroperative transrectal ultrasonography-guided bladder neck dissection ease the learning of robot-assisted laparoscopic prostatectomy?"
            ]
        },
        {
            "id": "task847-df5031fa1e3a474ba727fe3985414560",
            "input": "On cross-linking of receptor-bound IgE antibodies by allergens, effector cells (basophils and mast cells) involved in type I allergic reactions degranulate and release the potent chemical mediators stored inside their granules. Total and allergen-specific IgE concentrations, IgE affinity for allergen, and IgE clonality are all distinct properties of allergic patients' IgE repertoires. However, the inability to isolate individual IgE antibodies from allergic patients' sera presents a major barrier to understanding the importance of patient-specific IgE repertoires for the manifestation and severity of allergic symptoms.\", 'We sought to investigate how individual properties of an IgE repertoire affect effector cell degranulation.', 'A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized in regard to Der p 2 affinity, as well as Der p 2 epitope specificity, by using surface plasmon resonance technology. Human basophils were sensitized with different combinations of rIgEs, and degranulation responses were measured by means of flow cytometry after challenge with Der p 2.', 'A total of 31 Der p 2-specific rIgEs were produced. They bound a total of 9 different Der p 2 epitopes in the affinity range (K(D) value) of 0.0358 to 291 nM. Factors increasing human basophil degranulation were increased total IgE concentrations, increased concentrations of allergen-specific IgE relative to non-allergen-specific IgE, more even concentration of individual allergen-specific IgE clones, increased IgE affinity for allergen, and increased number of allergen epitopes recognized by the IgE repertoire (increased IgE clonality).",
            "output": [
                "Do several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge?"
            ]
        },
        {
            "id": "task847-0ea143a8a4594dd5b8ce471cc4bc53d6",
            "input": "The significance of high triglyceride levels as a risk factor for coronary heart disease is uncertain. We hypothesized that oral glucose tolerance test (OGTT) and certain novel markers may help to identify high-risk patients.', 'We recruited 80 subjects with severe hypertriglyceridemia (age 27-73 years) without clinical proteinuria and diabetes mellitus (DM) which were diagnosed by fasting glucose <126 mg/dL from Hyperlipidemia Clinic of National Taiwan University Hospital for this study. We applied OGTT to evaluate occult DM and homeostasis model assessment (HOMA)-insulin resistance (IR) score to evaluate insulin resistance, and the measurements of microalbuminuria as a marker of vascular damage. In addition, serum or plasma markers of inflammation and fibrinolysis, fasting glucose and insulin as well as traditional cardiovascular risk factors were also evaluated.', 'The serum level of triglyceride was higher in patients with microalbuminuria than in those without (14.1+/-5.7 vs. 9.6+/-3.9 mmol/L, p=0.025). Patients with microalbuminuria had higher fasting blood glucose and insulin, higher post-OGTT glucose and insulin, higher prevalence of newly developed diabetes mellitus (DM) (39% vs. 11%, p=0.007) and higher HOMA-IR (6.2+/-4.4 vs. 3.3+/-2.0, p<0.001). Among all the inflammatory and fibrinolytic markers, only soluble intercellular adhesion molecule showed significant different between these two groups. Multiple logistic regression analysis showed that among the serum markers, only HOMA-IR level was significantly related to microalbuminuria.",
            "output": [
                "Is insulin resistance the major determinant for microalbuminuria in severe hypertriglyceridemia : implication for high-risk stratification?"
            ]
        },
        {
            "id": "task847-a5947ed2cbd6410c9ebd53f0656b6f93",
            "input": "Previous studies have shown that giving other foods while breastfeeding increases the risk of mother-to-child transmission of human immunodeficiency virus (HIV) type 1. The mechanism is speculated to be increased inflammation of the gastrointestinal tract.', 'In a prospective longitudinal study, we compared fecal calprotectin, a marker of intestinal inflammatory disease, in healthy U.S. infants 0-6 months of age who were exclusively breastfed compared to those given additional liquids or solids.', 'In comparison to infants who were mixed-fed, fecal calprotectin was significantly higher in the exclusively breastfed group (p = 0.01) by a mean of 60 mg/kg (SE = 23).",
            "output": [
                "Are fecal calprotectin concentrations higher in exclusively breastfed infants compared to those who are mixed-fed?"
            ]
        },
        {
            "id": "task847-c4ceed2c611b40f6ada08e7849a83997",
            "input": "Obstetric complications involving birth hypoxia are implicated in the etiology of disorders with dopaminergic dysfunction, such as schizophrenia. Cesarean section (C-section) birth in both humans and rats is associated with increased mild respiratory distress and with reduced levels of circulating catecholamines at birth, which normally serve to prime the lungs and activate other processes promoting extrauterine adaptation. Using a rat model, it has been found that C-section birth can produce long-term changes in central nervous system (CNS) dopamine function, compared to vaginal birth.', 'The present experiments tested if administering exogenous epinephrine at birth could reverse long-term changes in dopaminergic parameters in C-sectioned rats.', 'In the absence of stress at adulthood, no differences were observed between C-sectioned and vaginally born rats in levels of in vivo tyrosine hydroxylase (TH) activity and dopamine transporter (DAT) binding. However, after repeated mild stress at adulthood, C-sectioned rats showed increased TH activity in nucleus accumbens and increased DAT in dorsal striatum and accumbens, compared to vaginally born controls. A single injection of epinephrine to C-sectioned rats just after birth prevented the increased TH activity and DAT binding seen in C-sectioned rats after repeated mild stress at adulthood. There was also a trend for epinephrine at birth to partially reverse an increase in amphetamine-induced locomotion seen in C-sectioned rats at adulthood.",
            "output": [
                "Does epinephrine administration at birth prevent long-term changes in dopaminergic parameters caused by Cesarean section birth in the rat?"
            ]
        },
        {
            "id": "task847-4379cc4934b64476bcbc87ef33d493a3",
            "input": "Blood O(2) saturation and lactate concentration gradients from superior vena cava (SVC) to pulmonary artery (PA) occur in critically ill patients. These gradients (DeltaSO(2) and Delta[Lac]) may be positive or negative. We tested the hypothesis that positive DeltaSO(2) and Delta[Lac] are associated with improved survival in critically ill patients.', 'Multinational, prospective observational study conducted in six medical and surgical ICUs.', 'Consecutive sample of 106 adults requiring insertion of a pulmonary artery catheter (PAC). Average age was 59.5 +/- 15.5 years, APACHE II score was 15.5 +/- 6.7 (mean +/- SD). Main outcome measure was 28-day mortality.', 'None.', 'We drew blood samples from the proximal and distal ports of PACs every 6 h from the time of PAC insertion (Initial measurement) until its removal (Final measurement). Samples were analyzed for SO(2), [Lac], glucose concentration and blood gases. Hemodynamic measurements were obtained after blood samples. We monitored patients for 30.9 +/- 11.0 h. Overall mortality rate was 25.5%. More survivors had mean and final DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 than decedents (p < 0.01; p < 0.05 respectively). On the average, DeltaSO(2) and Delta[Lac] were positive in survivors and negative in decedents. Survival odds ratios for final measurements of DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 were 19.22 and 7.70, respectively (p < 0.05).",
            "output": [
                "Are central venous to mixed venous blood oxygen and lactate gradients associated with outcome in critically ill patients?"
            ]
        },
        {
            "id": "task847-8bebf04f55e94debb8a1feab8304ba76",
            "input": "Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study, we investigated whether anti-TNF-alpha antagonist-monoclonal antibody-infliximab administration alters circulating levels of resistin, a proinflammatory adipokine. We further assessed associations of circulating resistin concentrations with CRP and ESR levels, platelet counts and metabolic syndrome and demographic characteristics in RA patients on periodical treatment with infliximab.', 'We investigated 33 patients with RA on periodical treatment with infliximab. Serum resistin levels were determined immediately prior to and after infliximab infusion.', 'Upon infliximab administration, mean (SD) serum resistin concentrations (ng/ml) decreased from 21.9 (9.9) to 17.4 (8.9) (p=0.005). Also, a significant association between the mean ESR (r=0.405; p=0.03) and CRP (r=0.571; p=0.0005) from disease diagnosis and ESR (r=0.486; p=0.004), CRP (r=0.599; p=0.0005) and platelet count (r=0.559; p=0.0007) at the time of the study and baseline resistin levels was found.",
            "output": [
                "Does anti-TNF-alpha therapy modulate resistin in patients with rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-fd40b6e862b94801ace76c6e35d1a6df",
            "input": "The mechanism by which low dose methotrexate (MTX, the gold standard treatment for rheumatoid arthritis) exerts its anti-inflammatory effect in rheumatoid arthritis (RA) patients is still debated. Lately, the MTX immunosuppressive effect has been related to apoptosis, especially in active RA patients, with ROS involvement.', 'In the present research we investigated MTX oxidative effect and its ability to modulate immune balance in active versus non-active RA patients.', 'Our results show that MTX induces IL-10 secretion (a TH2 cytokine) and significantly reduces TH1 profile in Peripheral Mononuclear Cells (PMNC) derived from active RA patients (n=28). Additionally, we found that MTX modulates the immune status towards TH2 dominance by decreasing the IL-12R and the CXCR3 receptors typical for the TH1 population. Moreover, MTX was found to inhibit the production of nitric oxide (NO) in these patients, a phenomenon that might contribute to MTX action toward cytokine homeostasis. A significant correlation was found between MTX IL-10 induction and NO inhibition in active RA patients.",
            "output": [
                "Does methotrexate selectively modulate TH1/TH2 balance in active rheumatoid arthritis patients?"
            ]
        },
        {
            "id": "task847-4f73e4cf63c049888c05af0431efd770",
            "input": "We previously reported that human OA subchondral bone osteoblasts could be discriminated into two subpopulations identified by their levels of endogenous production (low [L] or high [H]) of PGE(2). Here, we investigated the OPG and RANKL expression levels, the histologic analysis of the subchondral bone as well as the osteoclast differentiation effect of osteoblasts on normal and both OA subpopulations (L and H), and further examined on the L OA osteoblasts the modulation of bone remodelling factors on the OPG and RANKL levels, as well as on the resorption activity.', 'Gene expression was determined using real-time PCR, PGE2 and OPG levels by specific ELISA, and membranous RANKL by flow cytometry. Histological observation of the subchondral bone was performed on human knee specimens. Osteoclast differentiation and formation was assayed by using the pre-osteoclastic cell line RAW 264.7. OPG and RANKL modulation on L OA osteoblasts was monitored following treatment with osteotropic factors, and the resorption activity was studied by the co-culture of differentiated PBMC/osteoblasts.', 'Human OA subchondral bone osteoblasts expressed less OPG than normal. Compared to normal, RANKL gene expression levels were increased in L OA and decreased in H OA cells. The OPG/RANKL mRNA ratio was significantly diminished in L OA compared to normal or H OA (p<0.02, p<0.03), and markedly increased in H OA compared to normal. Inhibition of endogenous PGE(2) levels by indomethacin markedly decreased the ratio of OPG/RANKL on the H OA. In contrast to H OA osteoblasts, L OA cells induced a significantly higher level of osteoclast differentiation and formation (p<0.05). Histological analysis showed a reduced subchondral bone on the L OA and an increased bone mass on the H OA compared to normal. Treatment of L OA osteoblasts with osteotropic factors revealed that the OPG/RANKL mRNA expression ratio was significantly reduced by vitamin D(3) and significantly increased by TNF-alpha, PTH and PGE(2), while IL-1Beta demonstrated no effect. OPG protein levels showed similar profiles. No true effect was noted on membranous RANKL upon treatment with IL-1Beta, PGE(2) and PTH, but a significant increase was observed with vitamin D3 and TNF-alpha. The resorption activity of the L OA cells was significantly inhibited by all treatments except IL-1Beta, with maximum effect observed with vitamin D(3) and PGE(2).",
            "output": [
                "Is the differential expression of osteoprotegerin ( OPG ) and receptor activator of nuclear factor kappaB ligand ( RANKL ) in human osteoarthritic subchondral bone osteoblasts an indicator of the metabolic state of these disease cells?"
            ]
        },
        {
            "id": "task847-b5854c8bbcbc44ada073b22cd6652ef3",
            "input": "To explore the effect of delta-opioid receptor (DOR) in electroacupuncture (EA) protecting the brain against acute ischemic injury.', 'Fifty-one rats were randomly divided into sham ischemia group, ischemia group, sham EA group, EA group, and EA+DOR antagonist (naltrindole) group. Transient focal cerebral ischemia (1 hour) was induced in rat brain by middle cerebral artery occlusion (MCAO) method. EA was applied on Shuigou (GV 26) and Neiguan (PC 6) for 30 min, starting immediately after the onset of reperfusion. Neurological deficit scores and volume of cerebral infarction were detected after 24-hour reperfusion. Other 12 rats were randomly divided into sham ischemia group, ischemia group, EA group and EA + naltrindole group. DOR protein expressions were assessed by Western blotting after 24-hour reperfusion.', 'In comparison with the ischemia group and sham EA group, EA significantly reduced ischemic infarction and neurological deficits (P<0.05); EA significantly increased the expression of 60 kD DOR protein (P<0.05) and tended to increase that of 36 kD DOR protein (P>0.05). When naltrindole was combined with EA, the naltrindole completely abolished the EA-induced protection in ischemic infarction and neurological deficits, and also arrested the expression of DOR.",
            "output": [
                "Does [ Electroacupuncture protect the brain against acute ischemic injury via up-regulation of delta-opioid receptor in rats ]?"
            ]
        },
        {
            "id": "task847-826e39dbebc04d1fb3e5aea54ca0fbd5",
            "input": "Genetic variability in hepatic uptake was recently shown to influence the disposition and cholesterol-lowering effects of statins. Ezetimibe, an inhibitor of the intestinal cholesterol uptake protein Niemann-Pick C 1 like 1, is another drug for which genetic polymorphisms of hepatic organic anion transporting polypeptides (OATPs) are expected to be of clinical relevance because ezetimibe undergoes intensive enterohepatic circulation for which hepatic uptake transporters may be rate-limiting determinants.', 'Using OATP1B3-, OATP2B1-, and OATP1B1-transfected HEK cells, including the OATP1B1 variants OATP1B1*1b and OATP1B1*5, we measured the uptake of ezetimibe and its glucuronide and we analyzed the competition with the common OATP-substrate bromosulfophthalein. Disposition and sterol-lowering effects of 20-mg ezetimibe were measured in 35 healthy participants genotyped for OATP1B1, ABCB1, ABCC2, and UGT1A1.', 'Ezetimibe glucuronide inhibited bromosulfophthalein uptake in all OATP-transfected cells (50% inhibitory concentration (IC50): 0.14-0.26 mumol/l) whereas ezetimibe was 30-100 times less potent. Only the glucuronide was accumulated significantly in cells expressing OATP1B1 and OATP2B1. Its uptake in cells expressing OATP1B1*1b and *5 was reduced. In-vivo studies showed there was a gene-dose-dependent decrease in the area under the curve of ezetimibe in participants with the OATP1B1*1b protein (*1a/*1a, N=12, 112+/-66 ngxh/ml vs. *1a/*1b, N=8, 88+/-39 ngxh/ml vs. *1b/*1b, N=5, 55+/-18 ngxh/ml; Jonkheere-Terpstra, P=0.041) and a tendency for increased glucuronide exposure (704+/-296 vs. 878+/-369 vs. 1059+/-363 ngxh/ml; P=0.092). Fecal ezetimibe excretion was significantly decreased whereas renal glucuronide excretion was increased in carriers of *1b/*1b. Fecal excretion was also diminished in carriers of OATP1B1*5 and *15. The sterol-lowering effect of ezetimibe was not influenced by OATP1B1 polymorphisms.",
            "output": [
                "Is disposition of ezetimibe influenced by polymorphisms of the hepatic uptake carrier OATP1B1?"
            ]
        },
        {
            "id": "task847-61b3ef00f7ae422a9db3a831b1131a0a",
            "input": "The single nucleotide polymorphism rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene is associated with QTc prolongation, through an effect on the intracellular Ca levels. As sulfonylurea stimulate insulin secretion by an increased influx of Ca, we hypothesized that this polymorphism is associated with the glucose-lowering effect and mortality risk in sulfonylurea users.', 'Associations between the NOS1AP polymorphism, prescribed doses, and mortality rates in sulfonylurea, metformin, and insulin users were assessed in the Rotterdam Study, a population-based cohort study of 7983 elderly people.', 'We identified 619 participants who were prescribed oral antidiabetic drugs during follow-up. In glibenclamide users carrying the TG genotype, the prescribed doses were higher compared with the glibenclamide users carrying the TT genotype [0.38 defined daily dose units, 95% confidence interval (CI) 0.14-0.63]. Glibenclamide users with the TG or GG genotype had an increased mortality risk compared with glibenclamide users with the TT genotype [hazard ratio (HR) 2.80, 95% CI: 1.09-7.22]. Tolbutamide users with the TG or GG genotype (HR: 0.30, 95% CI: 0.14-0.63) and glimepiride users with the TG or GG genotype (HR: 0.18, 95% CI: 0.04-0.74) had a decreased mortality risk compared with tolbutamide and glimepiride users with the TT genotype.",
            "output": [
                "Is common variation in the NOS1AP gene associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea?"
            ]
        },
        {
            "id": "task847-4607bc3a4b2a4aff9d4f37f8475ba930",
            "input": "Folates provide one-carbon units for nucleotide synthesis and methylation reactions. A common polymorphism (677C-->T) in methylenetetrahydrofolate reductase (MTHFR) encodes an enzyme with reduced activity. Response to the antifolate methotrexate (MTX) may be modified in 677TT individuals because MTHFR converts nonmethylated folates, used for thymidine and purine synthesis, to 5-methyltetrahydrofolate, used in homocysteine remethylation to methionine. To study potential interactions between MTHFR activity and MTX, we examined the impact of decreased and increased MTHFR expression on MTX response in mice.', \"Mthfr-deficient (Mthfr and Mthfr) and wild-type (Mthfr) mice were injected with MTX or saline and assessed for hematological parameters (hematocrit, hemoglobin, red, and white blood cell numbers), plasma homocysteine, nephrotoxicity, hepatotoxicity, and splenic 2'-deoxyuridine 5'-triphosphate/2'-deoxythymidine 5'-triphosphate ratios. MTHFR-overexpressing transgenic mice (MTHFR-Tg) were generated, metabolites and folate distributions were measured, and response to MTX was assessed.\", \"MTX-treated Mthfr and Mthfr mice displayed hyperhomocysteinemia and decreased hematocrit, hemoglobin, and red blood cell numbers compared with wild-type animals. Mthfr mice also showed increased nephrotoxicity and hepatotoxicity. MTHFR-Tg mice were generated and confirmed to have increased levels of MTHFR with altered distributions of folate and thiols in a tissue-specific manner. After MTX treatment, MTHFR-Tg mice exhibited the same decreases in hematological parameters as Mthfr-deficient mice, and significantly decreased thymidine synthesis (higher 2'-deoxyuridine 5'-triphosphate/2'-deoxythymidine 5'-triphosphate ratios) compared with wild-type mice, but they were protected from MTX-induced hyperhomocysteinemia.",
            "output": [
                "Does altered expression of methylenetetrahydrofolate reductase modify response to methotrexate in mice?"
            ]
        },
        {
            "id": "task847-1a35596c5f7d4afe9e86af85d57facb7",
            "input": "Inside the cell, the HIV Tat protein is mainly found in the nucleus and nucleolus. The nucleolus, the site of ribosome biogenesis, is a highly organized, non-membrane-bound sub-compartment where proteins with a high affinity for nucleolar components are found. While it is well known that Tat accumulates in the nucleolus via a specific nucleolar targeting sequence, its function in this compartment it still unknown.', 'To clarify the significance of the Tat nucleolar localization, we induced the expression of the protein during oogenesis in Drosophila melanogaster strain transgenic for HIV-tat gene. Here we show that Tat localizes in the nucleoli of Drosophila oocyte nurse cells, where it specifically co-localizes with fibrillarin. Tat expression is accompanied by a significant decrease of cytoplasmic ribosomes, which is apparently related to an impairment of ribosomal rRNA precursor processing. Such an event is accounted for by the interaction of Tat with fibrillarin and U3 snoRNA, which are both required for pre-rRNA maturation.",
            "output": [
                "Does the HIV Tat protein affect processing of ribosomal RNA precursor?"
            ]
        },
        {
            "id": "task847-5b273a7e848b4214bf0f70b54fb2ce1e",
            "input": "Nondiagnostic fine-needle aspiration biopsy (ND-FNAB) of the thyroid leads to unnecessary thyroidectomy. The aims of this study were as follows: (1) to determine the risk of malignancy in ND-FNABs, and (2) to evaluate factors that may identify patients at risk for a ND-FNAB.', 'A total of 241 patients who underwent FNAB and thyroidectomy were evaluated for factors associated with a ND-FNAB.', 'A total of 215 women and 26 men underwent FNAB and thyroidectomy. ND-FNAs occurred in 51 of 241 (21%) patients. Ultrasound guidance did not reduce the likelihood of a ND biopsy. Patients with nodules greater than 3 cm had more ND-FNAs. Twenty-one of 51 with a ND biopsy underwent a repeat FNAB. Repeat FNAB was ND in 29% of patients. There was malignant disease in 7 of 51 (14%) with a ND-FNAB. Patient age, sex, thyroid function, gland size, multiple nodules, and final pathology were not related to a ND-FNAB (P > .05).",
            "output": [
                "Are nondiagnostic thyroid fine-needle aspiration biopsies no longer a dilemma?"
            ]
        },
        {
            "id": "task847-6a00653b491a4cd4b42aced5250fbc6c",
            "input": "To investigate the expression of scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXC chemokine ligand 16 (CXCL16) in the human monocyte-derived cell line THP-1, and the effect of lentiviral vectors for the stable delivery of SR-PSOX/CXCL16 short hairpin RNA on foam cell formation.', 'A lentiviral expression vector containing enhanced green fluorescence protein (GFP) and SR-PSOX small interfering RNA (siRNA) (Lenti-SR-PSOXsi), or the control siRNA (Lenti-NC) gene was constructed. A human monocyte-derived cell line THP-1 was transfected with a different multiplicity of infection (MOI) of Lenti-SR-PSOXsi or Lenti-NC, and cultured to obtain stably-transfected THP- 1KD and THP-1NC cells. After incubation with oxidatively-modified, low-density lipoprotein (Ox-LDL), the expression of SR-PSOX/CXCL16 mRNA was determined by real-time PCR. The expression of the SR-PSOX/CXCL16 protein was detected by flow cytometry analysis. The effect of Lenti-SR-PSOXsi on foam cell formation was assessed by Oil red O-stain analysis.', 'Ox-LDL increased the expression of SR-PSOX/CXCL16 mRNA in a time- and dose-dependent manner in THP-1 cells. Four days after transfection with Lenti-SR-PSOXsi (MOI: 100), the percentage of GFP expression cells was over 89.3%. The expression of the SR-PSOX/ CXCL16 mRNA and protein in THP-1KD cells significantly decreased compared with the parent cells, even the THP-1KD cells stimulated with 40 mg/L Ox-LDL. Ox-LDL uptake experiments in THP-1- and THP-1KD-derived macrophages indicated that SR-PSOX/CXCL16 deficiency decreased the development of macrophage- derived foam cell formation.",
            "output": [
                "Does lentiviral vector-mediated siRNA knockdown of SR-PSOX inhibit foam cell formation in vitro?"
            ]
        },
        {
            "id": "task847-eafc4e1dbd1d4deb9cad6d8394f901e2",
            "input": "The renin-angiotensin system (RAS) plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. In the past few years, angiotensin (Ang) (1-7) has been reported to counteract the effects of Ang II and was even considered as a new therapeutical target in RAS. The present study aimed to investigate the effect of Ang (1-7) administration on a diabetic animal model and the modulation on local RAS.', 'Streptozotocin (STZ) injection-induced diabetic rats were used in the experiment. The animals were divided into 3 groups: (1) control; (2) STZ-induced diabetes; and (3) STZ-induced diabetes with chronic Ang (1-7) treatment [D+Ang(1-7)]. In the D+Ang(1-7) group, a dose of 25 microg x kg(-1) x h(-1) of Ang (1-7) was continually injected through the jugular vein by embedding miniosmotic pump for 6 weeks. Plasma glucose, ratio of kidney to body weight, and 24 h urine protein and serum creatinine were monitored by conventional measurement. Plasma and renal Ang II levels were measured by radioimmunoassay. Ang-converting enzyme (ACE), ACE2, Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, Ang (1-7) Mas receptor, and TGF- beta1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF- beta1 protein levels were analyzed by Western blotting.', 'The renal function of diabetic rats was significantly retrogressed when compared with that of control rats. After the treatment by constant Ang (1-7) vein injection for 6 weeks, renal function was found to be even worse than diabetic rats, and both TGF-beta1 mRNA and protein levels were elevated in the D+Ang(1-7) group compared with the diabetic rats. The real-time PCR result also showed an increase in ACE mRNA expression and decrease in ACE2 mRNA level in the D+Ang(1-7) group when compared with diabetic rats. The number of AT1 receptors increased in the Ang (1-7)-injected group, while the number of AT2 and Mas receptors decreased.",
            "output": [
                "Does chronic angiotensin ( 1-7 ) injection accelerate STZ-induced diabetic renal injury?"
            ]
        },
        {
            "id": "task847-dc23b9f144a94229adb69225a7127121",
            "input": "Recent evidence has indicated that members of natural jasmonates, a family of plant stress hormones, exhibit anticancer activity. The current study was undertaken to investigate the effects of jasmonates on the in vitro growth of human neuroblastomas, one of the most common solid tumors in children.', 'Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide colorimetry and colony formation assay. Apoptosis was detected by Hoechst 33258 staining and flow cytometry. Western blotting was applied to assay gene expression.', 'The administration of natural jasmonates, methyl jasmonate, cis-jasmone, and jasmonic acid to cultured neuroblastoma cell line SH-SY5Y, resulted in a decrease of cell proliferation in a doseand time-dependent manner. However, the in vitro growth of cultured human embryonic kidney (HEK) cell line HEK 293 was not affected by jasmonates. The cell cycles of jasmonate-treated SH-SY5Y cells were arrested at the G2/M phase. The incubation of SH-SY5Y cells with jasmonates resulted in characteristic changes of apoptosis. The anticancer activities of natural jasmonates on SH-SY5Y cells are as follows: methyl jasmonate>cis-jasmone>jasmonic acid. In addition, the expressions of proliferating cell nuclear antigen and N-myc were downregulated by methyl jasmonate. Moreover, methyl jasmonate decreased the expression of the Xlinked inhibitor of apoptosis protein and survivin, critical members of inhibitors of the apoptosis protein family, in SH-SY5Y cells.",
            "output": [
                "Do natural jasmonates of different structures suppress the growth of human neuroblastoma cell line SH-SY5Y and its mechanisms?"
            ]
        },
        {
            "id": "task847-249ad61dd7a14c398d9c27369a0e4d09",
            "input": "The failure of in utero transplantation in immune-competent recipients suggests the existence of a fetal immune barrier. The importance of donor major histocompatibility complex (MHC) class I expression in the induction of prenatal tolerance remains undefined. We hypothesized that donor cell MHC class I expression facilitates engraftment in prenatal allogeneic recipients rather than promoting immune rejection.', 'B6.Ly5.2 (class I(+)) or B6.TAP(-/-) (class I(-)) murine fetal liver cells were transplanted into age-matched allogeneic fetal recipients. Survival to weaning and subsequent growth was assessed. Engraftment rates and peripheral blood chimerism levels were measured serially.', 'The presence or absence of class I expression did not affect survival or growth of recipients and no graft-vs-host disease developed. Allogeneic recipients of B6.Ly5.2 cells exhibited significantly higher levels of donor hematopoietic chimerism when compared to recipients of B6.TAP(-/-) cells (27% + 10% vs 11% + 8%; P = .004) that deteriorated further over time.",
            "output": [
                "Does donor major histocompatibility complex class I expression determine the outcome of prenatal transplantation?"
            ]
        },
        {
            "id": "task847-12eadb182d654cf88cbb0f2f94a78e34",
            "input": "A new protocol for postoperative calcium management was developed with the aim of achieving an increase in the proportion of patients being safely discharged on the first postoperative day. We present our experience with the first 50 patients treated under this new protocol.', 'A cohort study was performed involving the first 50 patients admitted for total or completion thyroidectomy, those data were then compared with a control group. Intact PTH (iPTH) was measured at 4-h postoperatively and patients with iPTH in the normal range were discharged on the first postoperative day.', 'Mean age and sex distribution were similar in both groups. Mean lowest postoperative corrected calcium levels in the study group were 2.19 mmol/l and 2.15 mmol/l in the control group (P = 0.24). Parathyroid auto-transplantation was associated with low PTH levels (risk ratio = 0.49). Over 50% of patients (n = 27) were successfully discharged on the first postoperative day in the study group and no patient required readmission. Length of stay was significantly shorter in the study group, mean 1.64 vs. 2.20 days (P < 0.05).",
            "output": [
                "Does postoperative PTH measurement facilitate day 1 discharge after total thyroidectomy?"
            ]
        },
        {
            "id": "task847-d3d0e56991b44c6ba704f475db352b51",
            "input": "The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and activation of functional responses, which include chemotaxis and generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis, but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Hu\u00ebt anomaly and the \"ichthyosis\" (ic) phenotype in mice. In this study, we have investigated roles for LBR in mediating neutrophil development and activation of multiple neutrophil functions, including chemotaxis and the respiratory burst.', 'A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses.', 'Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation.",
            "output": [
                "Do mouse neutrophils lacking lamin B-receptor expression exhibit aberrant development and lack critical functional responses?"
            ]
        },
        {
            "id": "task847-13a6a438e11341dc850e00f4e43d5ee0",
            "input": "Loss-of-function mutations in the progranulin gene (PGRN) were identified in frontotemporal lobar degeneration (FTLD) with ubiquitin-immunoreactive neuronal inclusions (FTLD-U). We assessed whether PGRN also contributes to genetic risk for Alzheimer disease (AD) in an extended Belgian AD patient group (n = 779, onset age 74.7 +/- 8.7 years).', 'A mutation analysis of the PGRN coding region was performed. The effect of missense mutations was assessed using in silico predictions and protein modeling. Risk effects of common genetic variants were estimated by logistic regression analysis and gene-based haplotype association analysis.', 'We observed seven missense mutations in eight patients (1.3%). Convincing pathogenic evidence was obtained for two missense mutations, p.Cys139Arg and p.Pro451Leu, affecting PGRN protein folding and leading to loss of PGRN by degradation of the misfolded protein. In addition, we showed that PGRN haplotypes were associated with increased risk for AD.",
            "output": [
                "Does genetic variability in progranulin contribute to risk for clinically diagnosed Alzheimer disease?"
            ]
        },
        {
            "id": "task847-c4c0aed80f524eef854d4d33fe33737c",
            "input": "Exposure to androgens early in development, while activating adaptive aggressive behavior, may also exert long-lasting effects on non-target components of phenotype. Here we compare these organizational effects of perinatal androgens in closely related Nazca (Sula granti) and blue-footed (S. nebouxii) boobies that differ in neonatal social system. The older of two Nazca booby hatchlings unconditionally attacks and ejects the younger from the nest within days of hatching, while blue-footed booby neonates lack lethal aggression. Both Nazca booby chicks facultatively upregulate testosterone (T) during fights, motivating the prediction that baseline androgen levels differ between obligately siblicidal and other species.', 'We show that obligately siblicidal Nazca boobies hatch with higher circulating androgen levels than do facultatively siblicidal blue-footed boobies, providing comparative evidence of the role of androgens in sociality. Although androgens confer a short-term benefit of increased aggression to Nazca booby neonates, exposure to elevated androgen levels during this sensitive period in development can also induce long-term organizational effects on behavior or morphology. Adult Nazca boobies show evidence of organizational effects of early androgen exposure in aberrant adult behavior: they visit unattended non-familial chicks in the colony and direct mixtures of aggression, affiliative, and sexual behavior toward them. In a longitudinal analysis, we found that the most active Non-parental Adult Visitors (NAVs) were those with a history of siblicidal behavior as a neonate, suggesting that the tendency to show social interest in chicks is programmed, in part, by the high perinatal androgens associated with obligate siblicide. Data from closely related blue-footed boobies provide comparative support for this interpretation. Lacking obligate siblicide, they hatch with a corresponding low androgen level, and blue-footed booby adults show a much lower frequency of NAV behavior and a lower probability of behaving aggressively during NAV interactions. This species difference in adult social behavior appears to have roots in both pleiotropic and experiential effects of nestling social system.",
            "output": [
                "Do perinatal androgens and adult behavior vary with nestling social system in siblicidal boobies?"
            ]
        },
        {
            "id": "task847-5d7a1da1178842aea0847ac1a7f6abc2",
            "input": "The Wave complex activates the Arp2/3 complex, inducing actin polymerization in lamellipodia and membrane ruffles. The Wave complex is composed of five subunits, the smallest of which, Brick1/Hspc300 (Brk1), is the least characterized. We previously reported that, unlike the other subunits, Brk1 also exists as a free form.', 'Here we report that this free form of Brk1 is composed of homotrimers. Using a novel assay in which purified free Brk1 is electroporated into HeLa cells, we were able to follow its biochemical fate in cells and to show that free Brk1 becomes incorporated into the Wave complex. Importantly, incorporation of free Brk1 into the Wave complex was blocked upon inhibition of protein synthesis and incorporated Brk1 was found to associate preferentially with neosynthesized subunits. Brk1 depleted HeLa cells were found to bleb, as were Nap1, Wave2 or ARPC2 depleted cells, suggesting that this blebbing phenotype of Brk1 depleted cells is due to an impairment of the Wave complex function rather than a specific function of free Brk1. Blebs of Brk1 depleted cells were emitted at sites where lamellipodia and membrane ruffles were normally emitted. In Brk1 depleted cells, the electroporation of free Brk1 was sufficient to restore Wave complex assembly and to rescue the blebbing phenotype.",
            "output": [
                "Is free Brick1 a trimeric precursor in the assembly of a functional wave complex?"
            ]
        },
        {
            "id": "task847-655501fcf72e4ec2b0c1ae73afe64b7f",
            "input": "To measure the prevalence of the Brugada type 1 ECG pattern in the general population in the Philippines. STUDY SETTING AND DESIGN: Sudden unexplained death syndrome is rare in the West but is common among Southeast Asians. Ventricular fibrillation is the terminal event. The Brugada type 1 electrocardiographic (ECG) pattern with J point and coved ST elevation in right precordial leads, is a marker for sudden unexplained death syndrome. Its prevalence in the general population is unknown. A cross-sectional nationwide survey was performed in the Philippines in 2003 using a stratified multistage sampling design covering all the regions and provinces in the country. ECGs were performed in all adults surveyed. The prevalences of the Brugada type 1 ECG pattern (coved type) and any type Brugada ECG pattern were determined.', 'The Brugada type 1 (coved) ECG pattern in the general population in the Philippines was found in 0.2% (95% Confidence Interval [CI] 0.03%-0.36%) of the population. Among males the prevalence was 0.3% (+/-0.1). The prevalence of any type Brugada ECG was 2% (95% CI 1.5%-2.6%).",
            "output": [
                "Is the Brugada type 1 electrocardiographic pattern common among Filipinos?"
            ]
        },
        {
            "id": "task847-36cd66d0bd8c4894865731205bbf848f",
            "input": "Early laparoscopic cholecystectomy (LC) results in a shorter length of stay and acceptable conversion and complication rates when compared with antibiotic therapy plus interval LC or percutaneous cholecystostomy in patients admitted to a surgical service because of acute cholecystitis. However, actual practice does not conform to current evidence.', 'Retrospective cohort study.', 'Urban teaching hospital.', 'Data were abstracted from the medical records of all patients with acute cholecystitis admitted to the surgical service via the emergency department during 36 months (October 1, 2002, to September 30, 2005). Patients were divided into 5 groups on the basis of treatment received. Length of stay, duration of symptoms, major complications, and conversion rates were analyzed.', 'Of 173 patients with acute cholecystitis, 71 (41%) underwent early LC. Of 102 patients treated with antibiotic therapy alone (59%), 57 were discharged; antibiotic therapy was unsuccessful in 45 patients. Of the patients in whom antibiotic therapy was unsuccessful, 26 underwent late LC and 19 underwent percutaneous cholecystostomy. Interval LC was eventually performed in 55 patients who did not undergo surgery during the index admission. Length of stay was significantly shorter in the early LC group compared with the interval LC group (P < .001). Conversion rates were not statistically different for the 3 LC groups (early LC, 5.6%; late LC, 11.5%; and interval LC, 9.1%). The only biliary complication occurred in the interval LC group.",
            "output": [
                "Is early laparoscopic cholecystectomy the preferred management of acute cholecystitis?"
            ]
        },
        {
            "id": "task847-f2ccd7952425469b97c21832fc348adb",
            "input": "Elevated myeloperoxidase (MPO) levels are predictive of high cardiovascular (CV) risk in the general population. The value of MPO as a CV marker in the HIV population has not been investigated.', 'Medical records were reviewed to identify HIV+ patients with a documented CV event (myocardial ischemia/infarction) and stored plasma samples within 12 months prior to the event. HIV+ adults with no CV history and with similarly available stored plasma samples were site-, age-, and gender-matched 1:1 to cases.', 'We identified 124 participants (62 case-control pairs): 94% male, median age 46 years. Median (IQR) MPO levels (pmoles/L) were lower in cases vs. controls: 292 (235-376) vs. 320 (249-467); p= .004. Cases were more likely to have other CV risk factors, including smoking, hypertension, and higher cholesterol and triglycerides. The observed MPO directional difference persisted after controlling for CV risk factors. In the reduced model, observed differences in MPO remained independently and negatively associated with CV event (p= .03) after adjusting for two positively associated risk factors, differences in cholesterol levels (p= .01), and differences in smoking history (ever smoked vs. never smoked; p= .04). Differences in triglyceride levels and hypertension were not statistically significant independent risk factors in this sample (p> .05). Within cases, MPO was negatively correlated with CD4 count (rs= -0. 40, p= .0023) and age (rs= -0. 34, p= .01). In contrast, age at blood draw was positively correlated with MPO in controls (rs= 0.28, p= .031) and CD4 was uncorrelated (rs= -0. 01, p> .9). No other factors were significantly correlated with MPO within groups.",
            "output": [
                "Are higher plasma myeloperoxidase levels associated with an increased risk for cardiovascular events in HIV-infected adults?"
            ]
        },
        {
            "id": "task847-9c5b82dcbfa6471fb4fe874bd771d9b3",
            "input": "Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man.', 'Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry.', 'Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls.",
            "output": [
                "Is the antithrombotic effect of dextran-40 in man due to enhanced fibrinolysis in vivo?"
            ]
        },
        {
            "id": "task847-020ce5d443744001b5ad767fbd2a2833",
            "input": "Operative management of patients with persistent N2 disease after induction therapy is still debated.', 'One hundred fifty-three consecutive patients underwent pneumonectomy from January 1999 until July 2005; 28 patients (18.3%) had persistent N2 disease after induction therapy (group 1), 32 patients (20.9%) had pathologic stage N0 or N1 after induction therapy (group 2), and 93 patients (60.8%) with pathologic N2 disease underwent immediate surgery (group 3). Short-term end points were operative mortality at 30 and 90 days and major complications. Long-term end points were 5-year survival and disease-free survival rates.', 'Demographics of the three groups were similar (age, sex, side of operation, type of chemotherapy, smoking status, and comorbidity such as coronary artery disease, diabetes, and chronic obstructive pulmonary disease). Thirty-day postoperative mortality was 10.7% in group 1, 3.1% in group 2 (p = 0.257), and 4.3% in group 3 (p = 0.201); 90-day postoperative mortality was 10.7% in group 1, 12.5% in group 2 (p = 0.577), and 9.7% in group 3 (p = 0.558). Incidence of major postoperative complications was similar. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). No statistical difference was found in terms of 5-year event-free survival, or regarding the side of pneumonectomy.",
            "output": [
                "Does persistent N2 disease after induction therapy jeopardize early and medium term outcomes of pneumonectomy?"
            ]
        },
        {
            "id": "task847-6f0c8669faf6481c8e4956be74502faf",
            "input": "To test the hypothesis that hot flashes specifically relate to verbal memory performance by examining the relationship between objective hot flashes and cognitive test performance in women with moderate to severe vasomotor symptoms.', 'In an observational study, 29 midlife women (mean age, 53 y) with moderate to severe hot flashes provided measures of objective hot flashes with an ambulatory hot flash monitor, subjective hot flashes with a diary and questionnaire, and objective measures of verbal memory and other cognitive functions with standardized neuropsychological tests.', 'The mean number of objective hot flashes was 19.5 per day (range, 6 to 35), including 15.3 (range, 6 to 35) during waking hours and 4.2 (range, 0 to 9) during sleep. The mean sensitivity (ie, subjective detection of objectively measured hot flashes) was 60%. Regression analyses revealed that total number of objective hot flashes, sleep duration, and verbal knowledge were significant predictors of delayed verbal memory. Verbal fluency correlated positively with objective daytime hot flashes. Hot flashes did not predict performance on any of the other secondary cognitive measures (ie, attention, working memory, visual memory), although poor sleep predicted worse performance on several outcome measures.",
            "output": [
                "Are objective hot flashes negatively related to verbal memory performance in midlife women?"
            ]
        },
        {
            "id": "task847-4ea65fa1362448c2b303097e04bd8f50",
            "input": "The objective of this study was to describe the relation of serum fatty acids and desaturase activity (DA) to overweight, insulin sensitivity and cardiovascular disease (CVD) risk factors in adolescents.', 'The relations of % serum phospholipid (PL) and cholesteryl ester (CE) fatty acids and estimated DA with CVD risk factors were examined in 264 adolescents (average age 15 years). Fatty acids were determined by gas liquid chromotography. Surrogate measures of DA were expressed as ratios of serum fatty acids: Delta9 DA=16:0/16:1; Delta6 DA=20:3,n6/18:2,n6 (PL) or 18:3,n6/18:2,n6 (CE); and Delta5 DA=20:4,n6/20:3,n6. Spearman partial correlations of fatty acids (%) and DA ratios with CVD risk factors were reported, adjusting for age, sex, race, Tanner stage, energy intake and physical activity.', 'Overweight adolescents compared to normal weight had more adverse levels of CVD risk factors, composition of PL and CE fatty acids in serum, and Delta6 DA and Delta5 DA ratios. Linoleic acid was inversely related to body mass index (BMI), waist circumference and triglycerides (P<or=0.01). Dihomo-gamma-linolenic acid was positively related to BMI, waist, insulin, and triglycerides, and inversely related to high-density lipoprotein-cholesterol levels (P<or=0.01). Delta6 DA was adversely associated with most of the risk factors (P<or=0.01), whereas triglycerides and fasting insulin were beneficially related to Delta5 DA (P<or=0.01).",
            "output": [
                "Are serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities related to overweight and cardiovascular risk factors in adolescents?"
            ]
        },
        {
            "id": "task847-440b7eb3db9749a68422f1f4c6798b11",
            "input": "Although several studies have investigated the association between cholesterol and dementia, few have examined cholesterol and decline across cognitive domains. We examined serum total and high-density lipoprotein (HDL) cholesterol, total-to-HDL ratio, and trajectories across cognitive domains.', \"Participants were 436 community-residing women (70-79 years old) in the Women's Health and Aging Study II; they were screened to be physically high-functioning and cognitively intact at baseline. Cognition and other health-related variables were assessed at five intervals spanning 9 years. Cognitive assessments included Trail Making Test Parts A (TMT-A) and B (TMT-B), Hopkins Verbal Learning Test-Revised, Purdue Pegboard, and Mini-Mental State Examination (MMSE). The association between baseline levels of serum lipids and cognitive trajectories were evaluated using Generalized Estimating Equations (GEE). Covariates included age, education, race, vascular disease, serum creatinine, depression, and lipid-lowering medications.\", 'In multivariate analyses, baseline higher total (p =.02) and HDL (p =.03) cholesterol were associated with better performance on the Purdue Pegboard. Using clinical cholesterol cutoffs, baseline serum total cholesterol levels >240 mg/dL were associated with the best performance (p =.02). Baseline lipids were not associated with any other cognitive tests; there were no Lipid x Time interactions.",
            "output": [
                "Is baseline serum cholesterol selectively associated with motor speed and not rates of cognitive decline : the Women 's Health and Aging Study II?"
            ]
        },
        {
            "id": "task847-b5177a40b10b41b4ba129372c248ee09",
            "input": "CXCL12 and CXCR4 signaling plays critical roles in development, homeostasis, and tumor metastasis. Previously, we have shown that epigenetic silencing of CXCL12 in colorectal and mammary carcinomas promotes metastasis. Anoikis is an essential process of colonic epithelial turnover and limits the metastatic progression of carcinoma. We sought to determine the role for anoikis in limiting tumor metastasis following reexpression of CXCL12 in human colorectal carcinoma cells.', 'Tumor formation and metastasis of colonic carcinoma cells was monitored using in vivo bioluminescence imaging. Anoikis was defined by using caspase-3/7, focal adhesion kinase (FAK) and p130Cas cleavage, DNA fragmentation, and cell survival assays. Phosphorylation of extracellular-regulated kinase-1/2 (ERK1/2) was monitored by immunoblot and immunohistochemistry, and activity was inhibited by using U0126.', 'Constitutive expression of CXCL12 in human colorectal carcinoma cells reduced orthotopic tumor formation and inhibited metastasis in severe combined immunodeficient mice. Further, CXCL12 expression induced apoptosis specifically in nonadherent colorectal carcinoma cells. Apoptotic cell death was preceded by hypophosphorylation and cleavage of FAK and p130Cas, leading to increased cellular detachment in culture, and depended on alterations in the extracellular matrix. Similar to in vivo colonic epithelium, CXCL12-induced anoikis of carcinoma cells depended on basal ERK1/2 activation.",
            "output": [
                "Does constitutive CXCL12 expression induce anoikis in colorectal carcinoma cells?"
            ]
        },
        {
            "id": "task847-fd86ab1787bb4ed0a901516ba0cea2d5",
            "input": "Regulation of the cytoskeleton is a central feature of cell migration. The formin family of proteins controls the rate of actin nucleation at its barbed end. Thus, formins are predicted to contribute to several important cell processes such as locomotion, membrane ruffling, vesicle endocytosis, and stress fiber formation and disassociation.', 'In this study we investigated the functional role of Formin1-isoform4 (Fmn1-IV) by using genetically null primary cells that displayed augmented protrusive behaviour during wound healing and delayed cell spreading. Cells deficient of Fmn1-IV also showed reduced efficiency of focal adhesion formation. Additionally, we generated an enhanced green fluorescence protein (EGFP)-fused Fmn1-IV knock-in mouse to monitor the endogenous subcellular localization of Fmn1-IV. Its localization was found within the cytoplasm and along microtubules, yet it was largely excluded from adherens junctions.",
            "output": [
                "Do formin 1-isoform IV deficient cells exhibit defects in cell spreading and focal adhesion formation?"
            ]
        },
        {
            "id": "task847-e7b7c65327eb4bf3a244b6c29c758e51",
            "input": "To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients.', \"Forty-three older PD patients (>or=65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method.\", 'Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum.",
            "output": [
                "Does voxel-based morphometry reveal extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism?"
            ]
        },
        {
            "id": "task847-5b9c38fde63542089882b8dd8e8c38e1",
            "input": "To observe the influence of hypoxia-inducible factor 1 alpha (HIF-1alpha) on angiogenesis in prostate carcinoma in vivo and to investigate its molecular mechanism.', 'LNCaP/HIF-1alpha and LNCaP cells were cultured, the level of PSA in the supernatant of the culture medium detected by ELISA assay before and after the transfection, and the cellular cycle measured by flow cytometry. Nude mouse models of subcutaneous tumor were established with LNCaP/HIF-1alpha and LNCaP cells, the tumor growth observed, and tumor specimens collected for immunohistochemical staining.', 'Compared with the LNCaP cells, LNCaP/HIF-1alpha cells showed an obviously decreased PSA level (t = 8.243, P < 0.05) and enhanced proliferous activity. The tumorigenesis rate increased and the tumorigenesis time advanced in the LNCaP/HIF-1alpha group of the nude mice. Immunohistochemistry displayed higher expressions of VEGF, iNOS and Ang-2 in the LNCaP/HIF-1alpha than in the LNCaP group.",
            "output": [
                "Does [ Over-expression of hypoxia-inducible factor 1 alpha increase angiogenesis of LNCaP cells in vivo ]?"
            ]
        },
        {
            "id": "task847-aa364d77594a4a8dbf62b1f22c2ceb67",
            "input": "Mutations of the beta-catenin (CTNNB1) gene are frequently found in adrenocortical tumors. This has important consequences to deregulate the expression of transcriptional targets of the Wnt pathway, which may contribute to tumorigenesis.', 'The objective of the study was to investigate the effect of the small-molecule inhibitor of the T cell factor (Tcf)/beta-catenin complex PKF115-584 on beta-catenin-dependent transcription and proliferation of H295R adrenocortical tumor cells, which harbor mutations in CTNNB1 as well as the TP53 tumor suppressor gene.', 'Immunofluorescence, transient transfection, proliferation assays, and flow cytometric analyses were used.', 'Nuclear localization of beta-catenin and constitutive activation of beta-catenin-dependent transcription was observed in H295R cells. PKF115-584 dose-dependently inhibited beta-catenin-dependent transcription and H295R proliferation, even in the presence of increased steroidogenic factor-1 levels, which augment proliferation in this cell line. The drug had no effect on HeLa cells, a cell line in which the beta-catenin pathway is not activated. PKF115-584 decreased the percentage of H295R cells in S-phase and increased the percentage of apoptotic cells.",
            "output": [
                "Does the T cell factor/beta-catenin antagonist PKF115-584 inhibit proliferation of adrenocortical carcinoma cells?"
            ]
        },
        {
            "id": "task847-79629e5168b145938fe839f6e3e0f480",
            "input": "Hyaluronic acid receptor is a glycoprotein of the plasmatic membrane, and the CD44 is its representative, expressed in many cell types where it has the task of cell adhesion.', 'the goal of the present experimental study is to investigate the possibility of using immunohistochemistry to identify the distribution of hyaluronic acid along the vocal fold.', 'We resected the normal vocal folds from a normal 23 year-old male black individual. The slides were analyzed by means of a histomorphometric study, comparing the color intensity in the superficial, middle and deep layers of the lamina propria. In the silanized slides we used immunohistochemistry, and evaluated the slides under light microscopy with 40x magnification, and the color changed to brown when there was a reaction with the receptor for hyaluronic acid.', 'Immunohistochemical findings showed the presence of hyaluronic acid receptors in the epithelium covering the vocal fold, being more concentrated in the central region of the vocal fold.",
            "output": [
                "Does detection of hyaluronic acid receptor in human vocal fold by immunohistochemistry?"
            ]
        },
        {
            "id": "task847-413b8622b2cb4c85b2f1e42c3b9eb635",
            "input": "We have previously demonstrated that sophorolipids, a class of easily chemoenzymatically modifiable glycolipids, possess anti-inflammatory effects in vitro and in vivo. Since glycolipids have been shown to have anticancer activity, we investigated the effects of sophorolipids and their derivatives against pancreatic cancer.', 'Human pancreatic carcinoma cells were treated with increasing concentrations of sophorolipid natural mixture or select derivatives (ethyl ester, methyl ester, ethyl ester monoacetate, ethyl ester diacetate, acidic sophorolipid [AS], lactonic sophorolipid diacetate [LSD]) for 24 h and assessed for cell necrosis (cytotoxicity-lactate dehydrogenase release). Controls consisted of cells treated with media or vehicle alone and sophorolipid treatment of peripheral blood mononuclear cells.', 'Sophorolipids demonstrated anticancer activity against human pancreatic carcinoma cells. Natural mixture mediated consistent cytotoxicity at all doses tested (20 +/- 4%). However, methyl ester derivative mediated much greater levels of cytotoxicity (63 +/- 5%) compared with other derivatives (ethyl ester diacetate, 36 +/- 6%, ethyl ester monoacetate, 18 +/- 7%; P < 0.05). In contrast, LSD- and AS-mediated toxicity was inversely proportional with dose (LSD, 40.3% at 0.5 mg/mL, 3.4% at 2.0 mg/mL; AS, 49% at 0.5 mg/mL, 0% at 2.0 mg/mL). Sophorolipid treatment did not affect peripheral blood mononuclear cells at all doses tested.",
            "output": [
                "Are sophorolipids and their derivatives lethal against human pancreatic cancer cells?"
            ]
        },
        {
            "id": "task847-8214fd2bfc5d4313bafe216141bc85ae",
            "input": "Cell signaling pathways underlying wound repair are under extensive investigation; however, there is still a poor understanding of the mechanisms orchestrating these processes. Hox genes, which are a subgroup of homeobox genes, encode for a family of transcription factors that play a critical role in tissue migration and cell differentiation during embryogenesis and may also serve as master regulatory genes of postnatal wound repair. We have developed a fetal excisional wound healing model whereby mid-gestational wounds heal in a regenerative manner while late-gestational wounds display scar formation. We theorize that Hoxd3 and Hoxd8 will be differentially expressed in mid- and late-gestational wounds compared with normal skin.', 'Pregnant FVB mice underwent hysterotomy at mid (E15)- or late (E18)-gestational time points, and 3-mm excisional wounds were made on the dorsum of each fetus. Wound samples (w) were collected at the site of injury as well as near wound normal skin (nwc) on the same fetus. Control (c) skin samples were also obtained from unwounded adjacent fetuses. Samples were harvested at 3 and 6 h and real-time polymerase chain reaction was performed for Hoxd3 and Hoxd8 and normalized to glyceraldehyde-3-phosphate dehydrogenase. Data were analyzed by analysis of variance with statistical significance of P < 0.05.', 'Hoxd3 levels were increased in all of the mid-gestational groups, with a significant increase at 3 h compared with late-gestational control groups. In the 3-h time group, Hoxd8 is increased in mid-gestational wounds compared with late-gestational control skin. This is repeated in the 6-h time group, where Hoxd8 is increased in mid-gestational wounds compared with all groups. Also, Hoxd8 in the mid-gestational near wound controls is significantly greater than that in the late-gestational near wound control and control groups.",
            "output": [
                "Are homeobox genes Hoxd3 and Hoxd8 differentially expressed in fetal mouse excisional wounds?"
            ]
        },
        {
            "id": "task847-78f0ae421a404a7d9aea4f0c04a42fc7",
            "input": "The effect of type 2 diabetes mellitus (adult-onset non-insulin-dependent), which is the most common form of diabetes in humans, on osseointegration capacity has not been addressed in an appropriate animal model. This study histologically and histomorphometrically examines bone healing around titanium implants in the type 2 diabetes rat model.', 'Titanium implants with a chamber were placed into the femurs of normal male rats and genetically modified male rats with a close symptomatic resemblance to human type 2 diabetes, as characterized by late-onset hyperglycemia and obesity. Cross-sectional histology for the tissue grown into the implant chamber was examined.', 'Bone volume around implants was consistently (from weeks 4 to 8 postimplantation) smaller for the diabetes group than for the control group in the cortical area, while the bone volume in the marrow area was not affected by the diabetes. Bone-implant contact percentage was considerably lower for the diabetes group in both the cortical and marrow areas, with the week 4 bone-implant contact in the cortical area being 12% for the diabetes group and 61% for the control group. A 2-fold difference remained at week 8. Bone morphogenesis in the diabetic rats was characterized by fragmented bone tissues and extensive soft tissue intervention.",
            "output": [
                "Does type 2 diabetes impair implant osseointegration capacity in rats?"
            ]
        },
        {
            "id": "task847-d19741d579ed4475ae14697541c6f38e",
            "input": "Most antiviral therapies directed against herpes simplex virus (HSV) infections are limited to a small group of nucleoside analogues that target the viral polymerase. Extensive clinical use of these drugs has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the need for the development of new anti-herpesviral drugs with novel targets. Herein the effects of a plant anthraquinone, emodin, on the HSV-1 alkaline nuclease activity and virus yields were investigated.', 'HSV-1 alkaline nuclease activity was examined by nuclease activity assay. Inhibition of virus yields was measured by plaque reduction assay and immunohistochemical staining. Interaction between emodin and alkaline nuclease was analysed by docking technology.', 'Emodin specifically inhibited the nuclease activity of HSV-1 UL12 alkaline nuclease in a biochemical assay. Plaque reduction assay revealed that emodin reduced the plaque formation with an EC(50) of 21.5+/-4.4 muM. Immunohistochemical staining using the anti-nucleocapsid protein antibody demonstrated that emodin induced the accumulation of viral nucleocapsids in the nucleus in a dose-dependent manner. Docking analysis further suggested that the inhibitory effect of emodin on the UL12 activity may result from the interaction between emodin and critical catalytic amino acid residues of UL12.",
            "output": [
                "Is emodin a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures?"
            ]
        },
        {
            "id": "task847-dd9e9728807f42ab95cc6ed94578e9e8",
            "input": "Tetrodotoxin (TTX) is used to distinguish between two classes of voltage-gated sodium channel (VGSC)--TTX sensitive (TTXS) and TTX resistant (TTXR). The resistance of TTXR VGSCs is thought to result from a low binding affinity of TTX, although at high TTX concentrations channel block does occur. Here, we show that, at concentrations below those which produce block, TTX can bind to TTXR VGSCs.', 'Whole-cell voltage clamp recordings were made from dissociated rat dorsal root ganglion neurones that expressed both TTXS and TTXR sodium currents. Voltage-gated calcium currents were blocked by 10 microM extracellular lanthanum chloride. TTXS, but not TTXR, current was suppressed by using a holding potential of -50 mV, and the effect of TTX on the isolated TTXR current was explored.', 'Extracellular application of 0.5 microM TTX produced a 40% increase in TTXR current amplitude, a negative shift in the voltage-dependence of current activation (approximately -8 mV) and inactivation (approximately -10 mV) and increased rates of current activation and inactivation. The effect of TTX on current amplitude was dose-dependent (EC50 = 364 nM). Removal of lanthanum prevented the effect of TTX on TTXR current amplitude, whereas reducing extracellular calcium did not.",
            "output": [
                "Do low concentrations of tetrodotoxin interact with tetrodotoxin-resistant voltage-gated sodium channels?"
            ]
        },
        {
            "id": "task847-481e194cc68044e088583e6cd9432a2f",
            "input": "Chemokines play a critical role in the pathogenesis of asthma and facilitate the recruitment of inflammatory cells in the airways. Evidence now suggests that airway smooth muscle (ASM) may serve as a source of chemokines in inflamed airways. Although vitamin D has potent anti-inflammatory properties in vitro in some cell types, its effects on ASM cells remain unclear. Here, we investigated whether 1alpha, 25-dihydroxy vitamin D3 (calcitriol) modulated chemokine production in ASM.', 'Human ASM cell cultures were derived from tracheal samples taken during surgery. ASM cells were treated with tumour necrosis factor alpha (TNFalpha) and/or interferon gamma (IFNgamma) for 24 h in the presence of calcitriol and/or the glucocorticoid fluticasone added 2 h before. RANTES (regulated upon activation, normal T-cell expressed and secreted), interferon-inducible protein 10 (IP-10) and fractalkine (FKN) levels in cell supernatants were measured by ELISA.', 'In TNFalpha-treated cells, calcitriol inhibited RANTES and IP-10 secretion in a concentration-dependent manner. FKN levels were negligible. In TNFalpha/IFNgamma-treated cells, whereas fluticasone or calcitriol alone partially inhibited RANTES secretion (by 38 and 20%, respectively), the combination of both drugs additively inhibited RANTES secretion (by 60%). No effect was observed on IP-10 secretion. Whereas fluticasone enhanced FKN secretion (by 50%), calcitriol significantly decreased FKN levels (by 50%). Interestingly, calcitriol blocked the stimulatory effect of fluticasone on FKN secretion, which was inhibited by 60% with the combination of calcitriol and fluticasone.",
            "output": [
                "Do vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells?"
            ]
        },
        {
            "id": "task847-cbc858269b6746deb011cbc91ff805a9",
            "input": "This study was undertaken to analyze and compare the clinical characteristics and survival difference among veterans and civilians in Taiwan with lung cancer, especially non-small-cell lung cancer, and to determine whether or not veterans have a poorer prognosis than civilians.', \"We retrospectively reviewed the medical records and computer files of lung cancer patients diagnosed between 1996 and 2000 at our hospital. Patients' clinical characteristics, marital status, staging, treatment modality, and overall survival were analyzed and compared, based on the patients' standing as veterans or civilians.\", 'During this period, 3,727 lung cancer patients (2,386 veterans, 1,341 civilians) were diagnosed. The overall survival of all lung cancer patients showed that civilians had better survival than veterans (median, 12 months vs. 8 months, p < 0.001). Survival of non-small-cell lung cancer patients was also better for civilians than veterans (median, 13 months vs. 9 months, p < 0.001). Surgery was the main treatment modality in both stage I and II civilians and veterans. A greater proportion of veterans in stage II and III received radiotherapy than civilians in the same stage, with a statistically significant difference in stage III patients (p < 0.001). Multivariate survival analysis showed that age and sex were independent risk factors for mortality, while standing (veteran or civilian) was not, in both all lung cancers and non-small-cell lung cancer alone.",
            "output": [
                "Is survival status of veterans with lung cancer poorer than that among civilians due to age and sex differences : a study of Chinese veterans in Taiwan?"
            ]
        },
        {
            "id": "task847-82663bf68f704a9fb73990451980357f",
            "input": "The hepatitis B virus (HBV) pol gene overlaps the S gene encoding surface antigen (HBsAg). It has been reported previously that drug-induced changes in HBsAg alter its binding to sera from humans immunized against HBV. We investigate here the changes to specific epitopes in the a determinant (the major target of neutralizing antibody) caused by a number of drug-resistant mutations.', 'Recombinant HBsAgs, produced by transfection of Chinese hamster ovary cells with S gene plasmids into which lamivudine, adefovir and entecavir resistance and common antibody-escape mutations had been introduced, were probed with monoclonal antibodies to epitopes in the first and second loops of the a determinant.', 'The mutations rtF166L/sF158Y (lamivudine-associated, compensatory) and rtl169T/sF161L (entecavir-associated, primary) acting alone, and the mutations rtV173L/sE164D (lamivudine-associated, compensatory) and rtSilent/sD144E (antibody escape-associated) each when combined with rtM204V/sl195M (lamivudine-associated, primary) led to decreases in antibody reactivity to epitopes in the first or second loop, or in both loops. The rtM204V/sl195M + rtV173L/sE164D mutations yielded an epitope-antibody profile similar to the rtR153Q/sG145R vaccine escape mutant. The rtM204V/sl195M mutation combined with the rtF166L/sF158Y or rtR153Q/sG145R mutation restored reactivity to second-loop epitopes previously abrogated by single mutations.",
            "output": [
                "Do antiviral resistance mutations potentiate hepatitis B virus immune evasion through disruption of its surface antigen a determinant?"
            ]
        },
        {
            "id": "task847-d73296b8d22f4fcf98723d05e5bb11ba",
            "input": "The gastric mucosa provides a stringent epithelial barrier and produces acid and enzymes that initiate digestion. In this regenerating tissue, progenitors differentiate continually into 4 principal specialized cell types, yet underlying mechanisms of differentiation are poorly understood. We identified stomach-restricted expression of the forkhead transcription factor FOXQ1.', 'We used a combination of genetic, histochemical, ultrastructural, and molecular analysis to study gastric cell lineages with respect to FOXQ1.', 'Within the developing and adult gastrointestinal tract, Foxq1 messenger RNA (mRNA) is restricted to the stomach and expressed predominantly in foveolar (pit) cells, the abundant mucin-producing cells that line the mucosal surface. Mice carrying Foxq1 coding mutations show virtual absence of mRNA and protein for the backbone of the major stomach mucin MUC5AC. These observations correspond to a paucity of foveolar cell secretory vesicles and notable loss of stomach but not intestinal mucus. Transcriptional profiling identified a surprisingly restricted set of genes with altered expression in Foxq1 mutant stomachs. MUC5AC is a highly tissue-restricted product that similarly depends on FOXQ1 in its other major site of expression, conjunctival goblet cells.",
            "output": [
                "Does transcription factor foxq1 control mucin gene expression and granule content in mouse stomach surface mucous cells?"
            ]
        },
        {
            "id": "task847-7f7b9787d06d47ee800b8bfd781fc401",
            "input": "In adults with growth hormone (GH) deficiency (GHD), GH treatment restores impaired endothelial function, a precursor of cardiovascular disease. Its effect in children with GHD is unknown.', 'Three months of GH (0.3 mg/kg/wk) were given to nine children with GHD. Endothelial function was measured via reactive hyperemic response. Forearm blood flow (FBF, strain gauge plethysmography) was measured before and after 5 min of upper arm arterial occlusion. Blood pressure and lipid, insulin and glucose levels were measured. Pretreatment endothelial function was compared to 18 previously studied control children.', 'Percent fall in forearm vascular resistance was greater in controls (81.2 +/- 1.9%) than in children with GHD (69.6 +/- 5.3%, p = 0.021) but was not affected by GH (60.6 +/- 7.5%). GH markedly increased HOMAIR (21 +/- 7 versus 43 +/- 8, p = 0.004). Plasma lipid levels did not significantly differ.",
            "output": [
                "Does growth hormone ( GH ) treatment restore endothelial function in children with GH deficiency?"
            ]
        },
        {
            "id": "task847-d726a10303c742899cf512976526f49a",
            "input": "To determine in a Phase I study the maximum tolerated dose of weekly gemcitabine concurrent with radiotherapy in locally advanced non-small-cell lung cancer (NSCLC), as well as the relationship between the volume of the esophagus irradiated and severe esophagitis.', 'Twenty-one patients with Stage III NSCLC received gemcitabine initially at 150 mg/m(2)/wk over 7 weeks concurrently with chest radiotherapy to 63 Gy in 34 fractions. The first 9 patients underwent treatment with two-dimensional (2D) radiotherapy; the remaining 12 patients, with three-dimensional conformal radiotherapy (3D-CRT) and target volume reduced to clinically apparent disease. Consolidation was 4 cycles of gemcitabine at 1000 mg/m(2)/wk and cisplatin 60 mg/m(2).', 'In the 2D group, the dose-limiting toxicity, Grade 3 esophagitis, occurred in 3 of 6 patients in the 150-mg/m(2)/wk cohort and 2 of 3 patients in the 125-mg/m(2)/wk cohort. No cases of Grade 3 esophagitis occurred at these doses in the 3D group. At gemcitabine 190 mg/m(2)/wk, 2 of 6 patients in the 3D cohort had Grade 3 esophagitis. The mean percentages of esophagus irradiated to 60 Gy were 68% in the 2D cohort and 18% in the 3D cohort.",
            "output": [
                "Is dose escalation of gemcitabine possible with concurrent chest three-dimensional rather than two-dimensional radiotherapy : a phase I trial in patients with stage III non-small-cell lung cancer?"
            ]
        },
        {
            "id": "task847-5146c000d08441978d166cb5f7d433d3",
            "input": "The present study was designed to examine the influence of suicidality on relapse in alcohol-dependent patients. Specifically, a lifetime suicide attempt at baseline was used to predict relapse in the year after treatment. Also, the unique contribution of impulsive suicide attempts was examined.', 'A total of 154 patients with alcohol dependence, consecutively admitted to four addiction treatment facilities in Warsaw, Poland participated in the study. Of the 154 eligible patients, 118 (76.6%) completed a standardized follow-up assessment at 12 months.', 'Previous suicide attempts were common in adults treated for alcohol dependence with 43% patients in the present sample reporting an attempt at some point during their lifetime. Additionally, more than 62% of those with a lifetime suicide attempt reported making an impulsive attempt. Lifetime suicide attempts were not associated with post-treatment relapse (chi-square=2.37, d.f.=1, p=0.124). However, impulsive suicide attempts strongly predicted relapse (OR=2.81, 95% CI=1.13-6.95, p=0.026) and time to relapse (OR=2.10, 95% CI=1.18-3.74, p=0.012) even after adjusting for other measures of baseline psychopathology, depression, impulsivity, hopelessness and alcohol use severity.",
            "output": [
                "Do impulsive suicide attempts predict post-treatment relapse in alcohol-dependent patients?"
            ]
        },
        {
            "id": "task847-e5f3a6f0782e4791ac6989646802713e",
            "input": "Tetrahydrocurcumin (THC) is an active metabolite of curcumin. It has been reported to have similar pharmacological activity to curcumin. The proteases that participate in extracellular matrix (ECM) degradation are involved in cancer cell metastasis. The present study investigates the effect of an ultimate metabolite of curcumin, THC, on the invasion and motility of highly-metastatic HT1080 human fibrosarcoma cells.', 'The effect of THC on HT1080 cell invasion and migration was determined using Boyden chamber assay. Cell-adhesion assay was used for examining the binding of cells to ECM molecules. Zymography assay was used to analyze the effect of THC on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) secretion from HT1080 cells. Tissue inhibitor of metalloproteinase (TIMP)-2 and membrane-type 1 matrix metalloproteinase (MT1-MMP) proteins levels were analyzed by Western blotting.', 'Treatment with THC reduced HT1080 cell invasion and migration in a dose-dependent manner. THC also decreased the cell adhesion to Matrigel and laminin-coated plates. Analysis by zymography demonstrated that treatment with THC reduced the levels of MMP-2, MMP-9, and uPA. THC also inhibited the levels of MT1-MMP and TIMP-2 proteins detected by Western blot analysis.",
            "output": [
                "Does tetrahydrocurcumin inhibit HT1080 cell migration and invasion via downregulation of MMPs and uPA?"
            ]
        },
        {
            "id": "task847-51b82c038d8f4605962050672e3b05f3",
            "input": "Neurotensin-1 (NT1) receptor agonists have been proposed as putative antipsychotic drugs. Recently, brain-penetrating NT analogs produced by stability-enhancing modification of the smallest NT fragment, NT(8-13), have demonstrated antipsychotic-like efficacy after acute systemic injection in several preclinical animal tests predictive for antipsychotic efficacy. However, the evidence regarding the persistence versus tolerance of these effects after repeated administration is ambiguous. Previous studies have used compounds that nonselectively activated both NT1 and NT2 receptors or used continuous slow, central infusion of doses rather than daily acute administration, both factors which may have contributed to the ambiguity in the literature regarding the emergence of tolerance.', 'To determine if tolerance develops to the antipsychotic-like effects of NT1 receptor agonists, we investigated the effects of subchronic daily systemic administration of PD149163, a brain-penetrating NT analog with selectivity for the NT1 receptor, on amphetamine-induced locomotor activation, a classic preclinical test of antipsychotic efficacy.', 'Sprague-Dawley rats were pretreated with eight consecutive daily subcutaneous (SC) injections of PD149163 or saline. On the ninth day, rats received a pair of SC injections consisting of PD149163 or saline, followed by amphetamine (0.5 mg/kg) or saline. Locomotor activity was then measured in photobeam-equipped cages.', \"The results indicated that repeated daily administration of PD149163 was able to antagonize amphetamine's locomotor-activating effect comparable to that of the first dose, despite that repeated administration of PD149163 produced an increase in baseline locomotor activity not seen after the first dose.",
            "output": [
                "Does the reversal of amphetamine-induced locomotor activation by a selective neurotensin-1 receptor agonist exhibit tolerance?"
            ]
        },
        {
            "id": "task847-c3495fa1b5aa46cfab836fc526fd7474",
            "input": "Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.', 'As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.', 'Twelve male SERT(+/+), SERT(+/-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L: -tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats.', 'Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats.",
            "output": [
                "Does acute tryptophan depletion dose dependently impair object memory in serotonin transporter knockout rats?"
            ]
        },
        {
            "id": "task847-9c46eef79a504cb89d9b43769e4cefbd",
            "input": "Only a few small studies have evaluated risk factors related to early death following emergency surgery for colonic cancer. The aim of this study was to identify risk factors for death within 30 days after such surgery.', 'Some 2157 patients who underwent emergency treatment for colonic cancer from May 2001 to December 2005 were identified from the national colorectal cancer registry. Thirty-day mortality rates were calculated and risk factors for early death were identified using logistic regression analysis.', 'The overall 30-day mortality rate was 22.1 per cent. The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11.7 (95 per cent confidence interval 8.8 to 15.5). Such complications occurred in 24.4 per cent of patients, of whom 57.8 per cent died. Other independent risk factors were age at least 71 years, male sex, American Society of Anesthesiologists grade III or more, palliative outcome, tumour perforation, splenectomy and adverse intraoperative surgical events. Postoperative surgical complications were noted in 20.4 per cent of the patients but had no statistically significant influence on mortality.",
            "output": [
                "Are postoperative medical complications the main cause of early death after emergency surgery for colonic cancer?"
            ]
        },
        {
            "id": "task847-1ea985c560ac48e4b43525a3fcaf133a",
            "input": "The immunoinhibitory receptor programmed death-1 (PD-1) is up-regulated on dysfunctional virus-specific CD8 T cells during chronic viral infections, and blockade of PD-1/PD-ligand (PD-L) interactions can restore their function. As hepatitis C virus (HCV) persists in the liver with immune-mediated disease pathogenesis, we examined the role of PD-1/PD-L pathway in antigen-specific CD8 T-cell dysfunction in the liver and blood of HCV-infected patients.', 'PD-1 expression and function of circulating CD8 T cells specific for HCV, Epstein-Barr virus, and influenza virus were examined ex vivo and following antigenic stimulation in vitro in patients with acute, chronic, and resolved HCV infection using class I tetramers and flow cytometry. Intrahepatic CD8 T cells were examined from liver explants of chronically HCV-infected transplant recipients.', 'Intrahepatic HCV-specific CD8 T cells from chronically HCV-infected patients were highly PD-1 positive, profoundly dysfunctional, and unexpectedly refractory to PD-1/PD-L blockade, contrasting from circulating PD-1-intermediate HCV-specific CD8 T cells with responsiveness to PD-1/PD-L blockade. This intrahepatic functional impairment was HCV-specific and directly associated with the level of PD-1 expression. Highly PD-1-positive intrahepatic CD8 T cells were more phenotypically exhausted with increased cytotoxic T-lymphocyte antigen 4 and reduced CD28 and CD127 expression, suggesting that active antigen-specific stimulation in the liver induces a profound functional exhaustion not reversible by PD-1/PD-L blockade alone.",
            "output": [
                "Is functional restoration of HCV-specific CD8 T cells by PD-1 blockade defined by PD-1 expression and compartmentalization?"
            ]
        },
        {
            "id": "task847-093e795dbb7f41739c76dc68bf190f6e",
            "input": "Green tea catechins are known to have anticarcinogenic effects. Epigallocatechin-3-gallate (EGCG) accounts for almost 50% of the total catechin content in green tea extract and has very potent antioxidant effects. EGCG also inhibits angiogenesis, possibly through the inhibition of proangiogenic factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which in turn, inhibits tumor growth and metastasis. However, the exact molecular mechanism by which EGCG suppresses bFGF expression is not known. Our objective was to elucidate the molecular mechanisms by which EGCG inhibits bFGF expression in colorectal cancer.', 'We examined posttranslational regulation of bFGF by EGCG in human colorectal cancer cells. We also examined bFGF in intestinal tumor formation of APC(Min/+) mice with and without catechin treatment.', 'The bFGF protein was quickly degraded in the presence of EGCG, but a proteasome inhibitor suppressed this degradation. EGCG was also found to increase ubiquitination of bFGF and trypsin-like activity of the 20S proteasome, thereby resulting in the degradation of bFGF protein. Furthermore, EGCG suppressed tumor formation in APC(Min/+) mice, compared with vehicle-treated mice, in association with reduced bFGF expression.",
            "output": [
                "Does a green tea component suppress posttranslational expression of basic fibroblast growth factor in colorectal cancer?"
            ]
        },
        {
            "id": "task847-bf7e9666640c4edc848a3691313a33cf",
            "input": "The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial.', 'We reviewed 434 patients who had undergone an initial resection for HCC and divided them into a multiple (n = 126) or single (n = 308) group according to the number of tumors. We also classified 386 of the patients into a PHT group (n = 136) and a no-PHT (n = 250) group according to whether they had PHT (defined by the presence of esophageal varices or a platelet count of <100,000/microL in association with splenomegaly).', 'Among Child-Pugh class A patients, the overall survival rates in the multiple group were 58% at 5 years, and 56% in the PHT group, which were lower than those in the single group (68%, P = .035) and the no-PHT group (71%, P = .008). Among Child-Pugh class B patients with multiple HCCs, the 5-year overall survival rate was 19%. Multivariate analyses revealed that the presence of multiple tumors was an independent risk factor for postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23-2.18; P = .001). A second resection resulted in satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups, as well as in the single (79%) or no PHT (81%) groups.",
            "output": [
                "Are neither multiple tumors nor portal hypertension surgical contraindications for hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-790e87fc89894629b8fd0003fd5750e8",
            "input": "No formal assessment of life expectancy in women with BRCA1 and BRCA2 mutations in these genes has been reported previously. We have evaluated life expectancy using actuarial analysis and assessed the effect of breast and ovarian cancers on premature death in >1,000 BRCA1/2 carriers.', 'Families with pathogenic mutations in BRCA1 and BRCA2 have been ascertained in a 10-million population region of United Kingdom since 1996. Mutation carriers and their first-degree relatives were used in an analysis of breast and ovarian cancer incidence and mortality as well as to derive and compare an actuarial assessment of life expectancy.', 'Six hundred twelve BRCA1 and 482 BRCA2 female mutation carriers were identified from 482 families. Life expectancy was significantly reduced for BRCA1 carriers compared with BRCA2 (P = 0.0002). This effect was attributable to an increased death rate from ovarian cancer (P = 0.04). Kaplan-Meier analysis revealed a better long-term survival from early-stage ovarian cancer in BRCA2 carriers but no significant differences in deaths from breast cancer or from women presenting with late-stage ovarian cancer. There was no other major contributing cause to death other than breast/ovarian cancer in BRCA1/2 female carriers.",
            "output": [
                "Is better life expectancy in women with BRCA2 compared with BRCA1 mutations attributable to lower frequency and later onset of ovarian cancer?"
            ]
        },
        {
            "id": "task847-b6651c8a20ff4201b11ee89d82efef5c",
            "input": "Supraclavicular brachial plexus blocks are not common in children because of risk of pneumothorax. However, infraclavicular brachial plexus blocks have been described in paediatric patients both with nerve stimulation and ultrasound (US)-guidance. US-guidance reduces the risk of complications in supraclavicular brachial plexus blocks in adults.', 'To compare the success rate, complications and time of performance of US-guided supraclavicular vs infraclavicular brachial plexus blocks in children.', \"Eighty children, 5-15 years old, scheduled for upper limb surgery were divided into two randomized groups: group S (supraclavicular), n = 40, and group I (infraclavicular), n = 40. All blocks performed were exclusively US-guided, by a senior anaesthesiologist with at least 6 months of experience in US-guided blocks. For supraclavicular blocks the probe was placed in coronal-oblique-plane in the supraclavicular fossa and the puncture was in-plane (IP) from lateral to medial. For infraclavicular blocks the probe was placed parallel and below the clavicle and the puncture was out-of-plane. Ropivacaine 0.5% was administered up to a maximum of 0.5 ml x kg(-1) until appropriate US-guided-spread was achieved. Block duration and volumes of ropivacaine used (mean+/-1SD) in the supraclavicular approach were recorded. Success rate (mean +/- 1 SD, 95%confidence interval), complications rate and time to perform the block (two-tailed Student's test) were recorded both for supraclavicular and infraclavicular approaches.\", \"In the US-guided supraclavicular brachial plexus blocks, the duration of the sensory block was 6.5 +/- 2 h and of the motor block was 4 +/- 1 h. The volume of ropivacaine used in this group was 6 +/- 2 ml. In group I, 88% of blocks achieved surgical anaesthesia without any supplemental analgesia compared with 95% in group S (P = 0.39; difference=7%; 95% CI: -10% to 24%). Failures in group I were because of arterial puncture and insufficient ulnar or radial sensory block. Failures in group S were because of insufficient ulnar sensory block. No pneumothorax or Horner's syndrome was recorded in either group. The mean time (SD) to perform the block was in group I: 13 min (range 5-16) and in group S: 9 min (range 7-12); the 95% CI for this difference was 2-6 min and was statistically significant (P < 0.05).",
            "output": [
                "Does ultrasound-guided supraclavicular vs infraclavicular brachial plexus block in children?"
            ]
        },
        {
            "id": "task847-9ad728ef7e954f33993492c7e25acd5b",
            "input": "Insect bites produce diverse skin reactions. Although quite common, the histopathologic features of arthropod assaults have not ever been studied systemically.', 'Twenty biopsies from cases, clinically diagnosed as arthropod bite reactions between January 2003 and June 2007 were reviewed retrospectively. The aim of the study was to verify as to whether reliable histopathologic criteria could be established based on the frequency of findings observed.', 'Epidermal spongiosis (present in 16 of 20 cases), in particular spongiosis of the infundibular epithelium and acrosyringia as well as eosinophilic spongiosis, emerge as relevant diagnostic clues. A moderately dense, superficial and deep infiltrate consisting mainly of lymphocytes and eosinophils was prevalent in the dermis, with eosinophils tending to interstitial and periadnexal distribution. Of note, 19 of 20 (95%) cases revealed periadnexal involvement, whereas 16 of 20 (80%) had the infiltrate extending particularly along the sweat ducts and the coiled glands. In three biopsies, concomitant involvement of sweat glands, hair follicles and sebaceous glands was noted.",
            "output": [
                "Does a histopathologic study of arthropod bite reactions in 20 patients highlight relevant adnexal involvement?"
            ]
        },
        {
            "id": "task847-f0de68c189614339adc7bd09e90404ea",
            "input": "To compare the temporal and spatial expression patterns of amyloid precursor protein (APP), amyloid-beta deposits, inflammatory chemokines, and apoptosis in the retina of a mouse model of Alzheimer disease (AD).', 'Retinas of transgenic mice harboring a mutant presenilin (PS1) and a mutant APP gene were processed for TUNEL and immunohistochemistry with antibodies against APP, amyloid-beta, monocyte chemotactic protein (MCP)-1, and F4/80. Comparisons were made between age groups and between transgenic and wild-type congeners.', 'The neuroretina demonstrated age-dependent increases in APP in the ganglion cells (RGCs) and in neurons of the inner nuclear layer (INL). Amyloid-beta demonstrated significant age-dependent deposition in the nerve fiber layer (NFL). TUNEL-positive RGC increased in an age-dependent fashion and in transgenic compared with wild-type congeners. Concomitant overexpression of MCP-1 and intense immunoreactivity for F4/80 suggested that RGCs upregulate MCP-1 in response to amyloid-beta. Activated microglia proliferated in response to MCP-1. In the outer retina, retinal pigment epithelium (RPE) demonstrated moderate age-dependent APP immunoreactivity, but nearby drusenlike deposits were not present. Amyloid-beta was observed in the choriocapillaris of the older animals.",
            "output": [
                "Do amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease?"
            ]
        },
        {
            "id": "task847-7cfd67390637460b9e77769602ea50f4",
            "input": "High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein and is released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. To test the hypothesis that HMGB1 enhances angiogenesis and restores cardiac function after myocardial infarction (MI), we generated transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) using alpha-myosin heavy chain promoter.', 'The left anterior descending coronary artery was ligated in HMGB1-Tg and wild-type littermate (Wt) mice. After coronary artery ligation, HMGB1 was released into circulation from the necrotic cardiomyocytes of HMGB1-overexpressing hearts. The size of MI was smaller in HMGB1-Tg than in Wt mice. Echocardiography and cardiac catheterization demonstrated that cardiac remodelling and dysfunction after MI were prevented in HMGB1-Tg mice compared with Wt mice. Furthermore, the survival rate after MI of HMGB1-Tg mice was higher than that of Wt mice. Immunohistochemical staining revealed that capillary and arteriole formation after MI was enhanced in HMGB1-Tg mice.",
            "output": [
                "Does high-mobility group box 1 restore cardiac function after myocardial infarction in transgenic mice?"
            ]
        },
        {
            "id": "task847-32483cd562f049548934bddaeea40bf8",
            "input": "Traditional methods for bile culturing may miss a large number of underlying bacterial infections that could lead to acute or chronic cholecystitis.', 'to evaluate possible differences regarding the site of material collection and thus to detect the most suitable sample site for gallbladder culture.', \"A cohort of 137 patients with symptomatic cholelithiasis was enrolled. After surgical excision of the gallbladder, bile cultures were separately performed from fundus, body and neck. Identification of bacteria as well as computation of mean bacterial concentrations were performed with standard microbiological techniques. Wilcoxon's paired and Chi-square tests were used for comparison between continuous and discrete parameters, respectively.\", 'Thirty-one patients (22.6%) demonstrated at least one positive culture sample. Positivity was 31/31 (100.0%) in neck samples, 20/31 (64.5%) in body and 13/31 (41.9%) in fundus samples (P<0.001). The microorganisms identified were Escherichia coli (14 cases) and Enterococcus faecalis (10 cases), followed by Staphylococcus aureus (3 cases), Pseudomonas aeruginosa, Enterococcus faecium, Enterobacter aerogenes and Enterobacter cloacae (1 case each). Mean bacterial concentrations in positive samples derived from the neck (272.2 +/- 187.5) were higher (P<0.01) when compared to those derived from both the body (38.2 +/- 28.7) and the fundus (12.5 +/- 11.3). Mean bacterial concentrations in positive samples derived from the body were higher (P<0.01) than those derived from the fundus.",
            "output": [
                "Does the culture site of the gallbladder affect recovery of bacteria in symptomatic cholelithiasis?"
            ]
        },
        {
            "id": "task847-46e339691b2a44768459e9a169fde954",
            "input": "The purpose of this study was to determine the effectiveness of laparoscopic cholecystectomy in children with biliary dyskinesia.', 'Reports of children with an abnormal cholecystokinin (CCK)-stimulated HIDA scan between January 2001 and July 2006 who underwent laparoscopic cholecystectomy were reviewed. Postoperatively, a 23-item Likert scale, symptom questionnaire was administered to parents.', \"Sixty-four children with chronic abdominal pain and no gallstones on ultrasound had an abnormal CCK-HIDA scan. Twenty-three children (median age, 14 years; 16 girls), with mean (SD) ejection fraction of 17% (8), underwent laparoscopic cholecystectomy and were further analyzed. Preoperatively, these children had right upper quadrant/epigastric pain (78%), nausea (52%), vomiting (43%), and generalized abdominal pain (22%) lasting for a median of 3 months (range, 1 month to 2.5 years). Median postoperative follow-up was 2.7 years. Sixteen (70%) parents completed the questionnaire. Of those who responded, 63% indicated that their children had no abdominal pain, 87% had no vomiting, and 69% had no nausea in the month preceding the questionnaire. Overall, 67% of parents indicated that their children's symptoms were completely relieved after cholecystectomy, whereas 7% indicated that the symptoms were not relieved.",
            "output": [
                "Does laparoscopic cholecystectomy for biliary dyskinesia in children provide durable symptom relief?"
            ]
        },
        {
            "id": "task847-2f4485c827fd4d409a79bec7469f519a",
            "input": "Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-alpha, an important autocrine stimulator of dendritic cells and macrophages in the airways.', 'We sought to study the mechanisms by which TNF-alpha and SP-D can affect cellular components of the pulmonary innate immune system.', 'Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro.', 'TNF-alpha, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-alpha release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-alpha, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures.",
            "output": [
                "Does surfactant protein D inhibit TNF-alpha production by macrophages and dendritic cells in mice?"
            ]
        },
        {
            "id": "task847-2663dbe0e8534d4abc7dc64da8cb1592",
            "input": "The incidence of chronic renal disease in women increases with aging, especially after menopause, suggesting that loss of sex hormones may contribute to the development and progression of renal disease. However, the mechanisms by which sex hormones, particularly estrogens, contribute to the disease process are unclear.', 'The present study examined the effects of ovariectomy (OVX) with or without 17 beta-estradiol (E2) supplementation (OVX+E2) on the expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase in the kidney.', 'The study was performed in young (4 months [4M]) and aged (12 months [12M]) female Dahl salt-sensitive rats fed a low-sodium (0.1% NaCl) diet. At 3 months of age, the animals were either subjected to sham surgery, OVX, or OVX with implantation of an E2 silastic pellet. The treatments were administered for either 1 or 9 months, rendering the animals 4 months of age or 12 months of age at the time of sacrifice, respectively. Renal expression of NOS isoforms was measured by Western blotting and immunohistochemistry.', 'OVX in the aged rats was associated with 35% and 25% decreases in medullary iNOS (mean [SEM] relative optical density [ROD]: 4M OVX, 1.81 [0.14] vs 12M OVX, 1.17 [0.16]; P < 0.05) and eNOS (mean ROD: 4M OVX, 1.91 [0.09] vs 12M OVX, 1.43 [0.15]; P < 0.05) protein expression, respectively, and a 25-fold increase in the abundance of CD68-positive cells, indicating macrophage infiltration (mean cells/mm2: 4M OVX, 1.18 [0.09] vs 12M OVX, 30.0 [0.74]; P < 0.001). E2 supplementation either partially or completely attenuated these changes in iNOS (mean ROD: 4M OVX+E2, 2.26 [0.08] vs 12M OVX+E2, 1.70 [0.09]; P < 0.05), eNOS (mean ROD: 4M OVX+E2, 2.03 [0.07] vs 12M OVX+E2, 1.77 [0.11]; P = NS) and CD68 (mean cells/mm2: 4M OVX+E2, 1.46 [0.07] vs 12M OVX+E2, 6.87 [1.6]; P < 0.01) associated with OVX in the aging kidney.",
            "output": [
                "Is age-related renal disease in female Dahl salt-sensitive rats attenuated with 17 beta-estradiol supplementation by modulating nitric oxide synthase expression?"
            ]
        },
        {
            "id": "task847-2318ab1413074ba4b5e1288a08f86278",
            "input": "To investigate whether unstimulated whole saliva flow rate (UFR) and osmolality (Sosm) track changes in hydration status during 48h of restricted fluid intake (RF) or combined fluid and energy restriction (RF+RE). Following the 48h periods, UFR and Sosm were assessed after acute exercise dehydration and rehydration.', 'Thirteen healthy males completed three trials in a randomised order: control (CON) where participants received their estimated energy (12,154+/-230kJ/d: mean+/-S.E.M) and fluid (3912+/-140ml/d) requirements, RF trial where participants received their energy requirements and 193+/-19ml/d water to drink (total fluid 960+/-15ml/d) and RF+RE where participants received 1214+/-25kJ/d and 962+/-16ml/d. After 48h, participants completed 30min of maximal exercise followed by rehydration (0-2h) and refeeding (2-6h).', 'At 48h body mass loss exceeded 3% on RF and RF+RE. UFR decreased during 48h on RF (510+/-122 to 169+/-37microl/min) and RF+RE (452+/-92 to 265+/-53microl/min) and was lower than CON at 48h (441+/-90microl/min: P<0.05). Sosm increased during 48h on RF (54+/-3 to 73+/-5mOsmol/kg) and RF+RE (52+/-3 to 68+/-5mOsmol/kg) and was greater than CON at 48h (52+/-2mOsmol/kg: P<0.05). Unlike UFR, Sosm identified the additional hypohydration associated with exercise (P<0.05) and returned to within 0h values with rehydration.",
            "output": [
                "Do saliva indices track hypohydration during 48h of fluid restriction or combined fluid and energy restriction?"
            ]
        },
        {
            "id": "task847-0700ac4eaa564d66bddcece6f1397088",
            "input": "To investigate the existence condition of hepatitis B surface antigen(HBsAg) termination codon bias.', 'A total of 174 reference sequences of all kinds of Hepatitis B virus(HBV) genotypes were chosen from GenBank, and compared by BioEdit. Then secondary structure of RNA was constructed and analyzed together.', '(1) There were two types of HBsAg termination codon: TAA and TGA in 174 reference sequences. TAA was in 124 cases (71.26%); and TGA in 50 cases (28.74%). (2) There was codon bias selection in HBsAg termination codon, and it could affect the secondary structure of RNA and amino acid sequence encoding protein.",
            "output": [
                "Does [ Hepatitis B surface antigen terminate codon bias selection ]?"
            ]
        },
        {
            "id": "task847-4fc8b5630ae04464bb6cd6532fb66936",
            "input": "To develop and assess clinical outcomes for osteochondral autografting for treatment of stifle osteochondrosis (OC) in dogs.', 'Retrospective case series.', 'Dogs with stifle OC (n=10).', 'Osteochondral autografting was developed and optimized in canine cadavers and purpose-bred research dogs using the Osteochondral Autograft Transfer System (OATS). Dogs with stifle OC (n=10 dogs, 12 stifles) were then treated using the OATS system. Outcomes were assessed by radiography (n=12), magnetic resonance imaging (1), second-look arthroscopy (9), lameness scoring (12), and telephone survey of owners (10 clients, 12 stifles) 6-15 months after surgery.', \"Complications were documented in 4 of the 12 stifles treated and included peri-incisional seromas (3) and marked stifle effusion (1). Subjective assessment of follow-up radiographs revealed evidence of integration of the grafts with maintenance of subchondral bone surface architecture. Subjective assessment of follow-up MRI in 1 stifle revealed evidence for incorporation of grafts with restoration of articular surface contour. Second-look arthroscopy 6-30 weeks after surgery revealed maintenance of articular cartilage at the graft site. Dogs were significantly (P<.001) less lame at follow-up compared with preoperative scores. Based on follow-up owner surveys, only 2 dogs had no pain or lameness; the other dogs were judged to have mild pain and/or lameness. All owners noticed improvement in the dogs' quality of life after surgery.",
            "output": [
                "Do autogenous osteochondral grafting for treatment of stifle osteochondrosis in dogs?"
            ]
        },
        {
            "id": "task847-4fdde6be71724c38bf4efa49aac8edba",
            "input": "Viral-mediated oncolysis is a novel cancer therapeutic approach with the potential to be more effective and less toxic than current therapies due to the agents selective growth and amplification in tumor cells. To date, these agents have been highly safe in patients but have generally fallen short of their expected therapeutic value as monotherapies. Consequently, new approaches to generating highly potent oncolytic viruses are needed. To address this need, we developed a new method that we term \"Directed Evolution\" for creating highly potent oncolytic viruses.', 'Taking the \"Directed Evolution\" approach, viral diversity was increased by pooling an array of serotypes, then passaging the pools under conditions that invite recombination between serotypes. These highly diverse viral pools were then placed under stringent directed selection to generate and identify highly potent agents. ColoAd1, a complex Ad3/Ad11p chimeric virus, was the initial oncolytic virus derived by this novel methodology. ColoAd1, the first described non-Ad5-based oncolytic Ad, is 2-3 logs more potent and selective than the parent serotypes or the most clinically advanced oncolytic Ad, ONYX-015, in vitro. ColoAd1\\'s efficacy was further tested in vivo in a colon cancer liver metastasis xenograft model following intravenous injection and its ex vivo selectivity was demonstrated on surgically-derived human colorectal tumor tissues. Lastly, we demonstrated the ability to arm ColoAd1 with an exogenous gene establishing the potential to impact the treatment of cancer on multiple levels from a single agent.",
            "output": [
                "Does directed evolution generate a novel oncolytic virus for the treatment of colon cancer?"
            ]
        },
        {
            "id": "task847-a4575268b4d447fda776acc93f7b8b19",
            "input": "To determine if bilateral S3 lead placement during the stage I trial period improves the \"success\" rate for advancing to stage II (permanent) sacral neuromodulator placement.', 'A retrospective chart review of 124 (20 male and 104 female) patients undergoing stage I sacral neuromodulation (InterStim, Medtronic, Minneapolis, Minnesota) implantation for the treatment of refractory voiding dysfunction was performed. Patients were divided into two cohorts based on unilateral versus bilateral stage I lead placement in the S3 foramina. Both groups were then evaluated and compared with regards to overall \"success\", defined as progression from stage I to stage II placement.', 'Fifty-five (44%) patients underwent unilateral stage I lead placement and 69 (56%) received bilateral S3 leads. Successful stage I trials were reported in 32/55 (58%) and 53/69 (76%) of unilateral and bilateral cohorts, respectively (P = 0.03). Five wound infections were reported-2 (3.6%) following unilateral and 3 (4.3%) after bilateral stage I lead placement. No other complications were encountered.",
            "output": [
                "Do unilateral versus bilateral stage I neuromodulator lead placement for the treatment of refractory voiding dysfunction?"
            ]
        },
        {
            "id": "task847-5ecbf8e87ce4480eade1bf58c08338bb",
            "input": "The aim of this research was to describe nomograms of brainstem auditory evoked potentials, oscillating stimulation of the vestibular organs and ultrastructural research methodology of a spiral organ of guinea-pigs.', \"For the experimental purposes 60 guinea-pigs of both sexes, weight 250-300 grams, were used as research materials. After general anesthesia with Ketalar dosed 100 milligrams per kilogram and with Fentanyl dosed 0.1 milliliter per kilogram of the body mass, brainstem auditory evoked potentials were registered and the oscillating chair test (no prior anesthesia). Was placed on an assistant's knees, who was sitting on a chair. Then the guinea-pigs were anesthetized with 35 per cent solution of chloral hydrate intraperitoneally (dosed 1 milliliter per kilogram of the body mass). For electron microscopic research membranous helix was collected bilaterally by the method of micropreparation. Qualitative observation was conducted in the Philips' electron microscope (EM 300).\", 'On the basis of the obtained results it was concluded that the time of transmission between elements P1-P2 is constant and figures between 3.1 and 3.6 ms independently from a force of stimulation. Vestibular organs of a guinea-pig are more sensitive to high accelerations (17-12 degree/s2) than human vestibularl organs. However, their reaction is much weaker to lower accelerations (12-0 degree/s2).",
            "output": [
                "Do [ Guinea pig as often object to otoneurological experimental examinations ]?"
            ]
        },
        {
            "id": "task847-f770e55994e748189acd0ab923953b08",
            "input": "To evaluate the adequacy of retrobulbar block anesthesia only in vitreoretinal surgery.', 'The study involved 90 patients, 25 who underwent 25-gauge transconjunctival sutureless vitrectomy and 65 who underwent 20-gauge standard pars plana vitrectomy. Twenty-five of the 90 patients also underwent combined phacoemulsification and posterior intraocular lens implantation. The efficacy of retrobulbar block anesthesia only was assessed by monitoring vital signs during surgery, reviewing patient responses to a questionnaire regarding their experience during surgery, and analyzing surgical outcomes.', 'Four patients complained of moderate pain during surgery, but no patient complained of severe pain. Infiltrative anesthesia was additionally required in 14 patients. No patient experienced intraoperative complications due to head movement. Increased systolic blood pressure greater than 15 mm Hg occurred in 11 patients and increased respiratory rate by 3 breaths per minute or greater occurred in 7 patients. Anatomical and functional success rates were 95% and 80%, respectively. Complications included manageable retrobulbar bleeding (1 patient) and postoperative neovascular glaucoma (2 patients).",
            "output": [
                "Do the efficacy of retrobulbar block anesthesia only in pars plana vitrectomy and transconjunctival sutureless vitrectomy?"
            ]
        },
        {
            "id": "task847-e305d259b54747549bdfb2ac6ccdc205",
            "input": "In this study, we compared the diagnostic performance of the standard SPECT with motion-frozen (MF) myocardial perfusion SPECT (MPS) in obese patients.', 'A total of 90 consecutive obese patients (body mass index, 30.1-46.8, average, 34.3 +/- 3.6; age, 63 +/- 12 y; 30% women) underwent standard supine rest (201)Tl/stress (99m)Tc dual-isotope gated MPS and cardiac catheterization within 3 mo. MF images were obtained by nonlinear warping of cardiac phases to the end-diastolic position. Total perfusion deficit (TPD) was obtained for summed (S-TPD) and motion-frozen (MF-TPD) datasets with sex-specific standard and MF normal limits.', 'The area under the receiver-operating-characteristic (ROC) curve for detection of coronary artery disease (CAD) by MF-TPD was significantly larger than that for S-TPD (0.93 +/- 0.25 vs. 0.88 +/- 0.32, P < 0.05). MF-TPD had higher specificity (77% vs. 55%, P < 0.05) and accuracy (89% vs. 80%, P < 0.05) than did S-TPD.",
            "output": [
                "Does motion-frozen myocardial perfusion SPECT improve detection of coronary artery disease in obese patients?"
            ]
        },
        {
            "id": "task847-b09fe98e481d4bf4949d5a8db2277eb7",
            "input": "Evidence for an association between phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) and schizophrenia was recently obtained and replicated in several samples. PIP5K2A controls the function of KCNQ channels via phosphatidylinositol-4,5-bisphosphate (PIP2) synthesis. Interestingly, recent data suggest that KCNQ channels suppress basal activity of dopaminergic neurons and dopaminergic firing. Activation of KCNQ accordingly attenuates the central stimulating effects of dopamine, cocaine, methylphenidate, and phenylcyclidine.', 'The aim of this study was to explore the functional relevance of PIP5K2A, which might influence schizophrenic behavior.', 'Here, we study the effects of the neuronal PIP5K2A on KCNQ2, KCNQ5, KCNQ2/KCNQ3, and KCNQ3/KCNQ5 in the Xenopus expression system.', 'We find that wild-type PIP5K2A but not the schizophrenia-associated mutant (N251S)-PIP5K2A activates heteromeric KCNQ2/KCNQ3 and KCNQ3/KCNQ5, the molecular correlate of neuronal M channels. Homomeric KCNQ2 and KCNQ5 channels were not activated by the kinase indicating that the presence of KCNQ3 in the channel complex is required for the kinase-mediated effects. Acute application of PI(4,5)P2 and a PIP2 scavenger indicates that the mutation N251S renders the kinase PIP5K2A inactive.",
            "output": [
                "Does a schizophrenia-linked mutation in PIP5K2A fail to activate neuronal M channels?"
            ]
        },
        {
            "id": "task847-8b655c56d37e436ebf8a1f16018ec5f7",
            "input": "Despite ubiquitous expression of the keratoepithelin (KE) protein encoded by the transforming growth factor beta induced/beta induced gene human clone 3 (TGFBI/BIGH3) gene, corneal dystrophies are restricted to the cornea, and no other tissues are affected. We investigated the role of TGFBI/BIGH3 in Groenouw corneal dystrophies by generating transgenic mice overexpressing TGFBI/BIGH3 containing the R555W mutation.', 'Transgenic animals expressing the Groenouw mutation of human TGFBI/BIGH3 were generated using lentiviral vectors. The line expressed TGFBI/BIGH3 containing the R555W mutation under the control of the phosphoglycerate kinase (PGK) promoter. Expression of the transgene was monitored by Southern and western blotting and by RT-PCR. Electroretinogram analysis was performed and four mice were subjected to complete necroscopy.', 'Transgene expression was observed in different organs although without specific expression in the cornea. The overall morphology of the transgenic animals was not severely affected by KE overexpression. However, we observed an age-dependent retinal degeneration both functionally and histologically. Female-specific follicular hyperplasia in the spleen and increased levels of lipofuscin in the adrenal gland were also seen in transgenic animals.",
            "output": [
                "Does overexpression of a mutant form of TGFBI/BIGH3 induce retinal degeneration in transgenic mice?"
            ]
        },
        {
            "id": "task847-2e634db7e782458c9e850a57e44f6ae9",
            "input": "Intermittent clamping of the porta hepatis, or the intermittent Pringle manoeuvre (IPM), is often used to control inflow during parenchymal liver transection. The aim of this study was to determine whether IPM is associated with an adverse long-term outcome after liver resection for colorectal liver metastasis (CRLM).', 'All patients undergoing resection for CRLM in 1993-2006, for whom data on IPM were recorded, were included in the study. A total of 563 patients was available for analysis.', 'IPM was performed in 289 (51.3 per cent) of the patients. The duration of IPM ranged from 2 to 104 (median 22) min. There were no differences in clinicopathological features or postoperative morbidity between patients who had an IPM and those who did not. The median survival of patients undergoing IPM was 55.7 months compared with 48.9 months in those not having an IPM (P = 0.406). There was no difference in median disease-free survival between the two groups (22.1 versus 19.9 months respectively; P = 0.199).",
            "output": [
                "Is intermittent Pringle manoeuvre associated with adverse long-term prognosis after resection for colorectal liver metastases?"
            ]
        },
        {
            "id": "task847-3c243fabbac64de2ad00d89f996bf04c",
            "input": "We evaluated the incidence of cryptorchidism and inguinal hernias in patients with posterior urethral valves, and compared characteristics in patients with and without cryptorchidism or inguinal hernia.', 'A total of 200 patients with posterior urethral valves treated between 1953 and 2003 were identified from a hospital database. Patient records were retrospectively reviewed. The state of testicular descent and the presence of inguinal hernias were recorded in 192 patients. Patient characteristics were analyzed.', 'Of 192 patients 31 (16%) had cryptorchidism, which was bilateral in 9 (29%). A total of 21 patients (11%) had inguinal hernias that were not associated with cryptorchid testes. The patients with cryptorchidism, and to some extent the patients with hernias, appeared to have a more severe form of posterior urethral valves than those without cryptorchidism. At the time of diagnosis the median serum creatinine concentration was 100 mumol/l (range 38 to 460) in boys with cryptorchidism and 87 (14 to 593) in boys without cryptorchidism (p = 0.131). At 6-month followup the median serum creatinine levels were 90 mumol/l (range 31 to 573) in patients with cryptorchidism and 45 (19 to 504) in patients without cryptorchidism (p = 0.006). Cryptorchidism was also more common in cases diagnosed neonatally compared to those diagnosed at a later age (14 of 52 patients, 27% vs 14 of 112, 12.5%, respectively, p = 0.027).",
            "output": [
                "Are posterior urethral valves often associated with cryptorchidism and inguinal hernias?"
            ]
        },
        {
            "id": "task847-3f5203dcca574087af9c4dbd67cd9246",
            "input": "Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America.', 'BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10(8.5+/-0.7) in control untreated animals to 10(5.0+/-0.0) in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10(15.5+/-0.5) parasites were quantified from untreated animals, as opposed to 10(5.1+/-0.1) parasites detected in treated mice.",
            "output": [
                "Is tamoxifen effective in the treatment of Leishmania amazonensis infections in mice?"
            ]
        },
        {
            "id": "task847-6dda0678bd644b3481fab62549a62585",
            "input": "There is a lack of agreement regarding preexisting portal vein thrombosis (PVT) in patients undergoing living donor liver transplantation (LDLT). We report the results of a single-center study to determine the impact of PVT on outcomes of adult LDLT recipients.', 'Of 133 cases of adult LDLT performed between January 2000 and December 2004, a thrombectomy was performed on 22 patients (16.5%) with PVT during the transplant procedure. One hundred eleven patients without PVT (group 1) were compared with those with a thrombosis confined to the portal vein (group 2; n = 15) and patients with the thrombosis beyond the portal vein (group 3; n = 7).', 'The sensitivities of Doppler ultrasound and CT in detecting PVT were 50 and 63.6%. A prior history of variceal bleeding (OR = 10.6, p = 0.002) and surgical shunt surgery (OR = 28.1, p = 0.044) were found to be an independent risk factors for PVT. The rate of postoperative PVT was significantly higher in patients with PVT than in those without (18.2 vs. 2.7%; p = 0.014). In particular, the rethrombosis rate in group 3 was 28.6%. The actuarial 3-year patient survival rate in PVT patients (73.6%) was similar to that of the non-PVT patients (85.3%; p = 0.351). However, the actuarial 3-year patient survival rate in group 3 was 38.1%, which was significantly lower than that in groups 1 and 2 (p = 0.006).",
            "output": [
                "Is thrombosis confined to the portal vein a contraindication for living donor liver transplantation?"
            ]
        },
        {
            "id": "task847-e4f0e323e8d24825a71b67ba99b6ee80",
            "input": "Children with heavy prenatal alcohol exposure have documented impairments in executive functioning (EF). One component of EF, concept formation, has not been well studied in this group.', 'Children (8 to 18 years) with histories of heavy prenatal alcohol exposure, with and without fetal alcohol syndrome (FAS), were compared to typically developing controls on 2 measures of concept formation and conceptual set shifting: the Wisconsin Card Sorting Test and the Card Sorting Test from the Delis-Kaplan Executive Functioning System. In addition to between-group comparisons, performance relative to overall intellectual functioning was examined.', 'Children with histories of heavy prenatal alcohol exposure showed impairment on both tests of concept formation compared to non-exposed controls. These deficits included difficulty generating and verbalizing concepts, increased error rates and perseverative responses, and poorer response to feedback. However, in comparison to controls, alcohol-exposed children performed better on measures of concept formation than predicted by their overall IQ scores. Exploratory analyses suggest that this may be due to differences in how the measures relate at different IQ levels and may not be specific to prenatal alcohol exposure.",
            "output": [
                "Do children with heavy prenatal alcohol exposure demonstrate deficits on multiple measures of concept formation?"
            ]
        },
        {
            "id": "task847-73b28fa1d75f48b48766b53fbb995bec",
            "input": "Clonal typing of neurogenic clones.', 'To determine whether neurogenic clones carried over weeks in the urine of asymptomatic children with neurogenic bladder were similar to known uropathogenic clones associated with disease.', 'Michigan State University; VA Medical Center, Minneapolis, MN, USA.', 'Escherichia coli isolates from the urine of 15 children previously followed were typed by multilocus sequence typing and compared to 2 human pyelonephritis genome strains, 29 pediatric or adult symptomatic urinary tract infection strains, 15 pediatric asymptomatic bacteriuria strains, 6 animal urinary tract infection strains and a neonatal meningitis-septicemia prototype K1 strain. Phylotypes and virulence genotypes were determined using PCR.', 'Twenty-nine E. coli isolates were classified into 15 clones. Six of 15 clones were the same sequence type or a close relative to a clone that caused disease in a human or animal. These clones were considered uropathogens. The remaining nine clones were not closely related to a clone that caused disease and were considered commensal clones. Uropathogens were predominantly group B2, exhibited more virulence genes and were carried for more weeks in the neurogenic bladder compared to commensal clones. Nine of 15 children carried one or more uropathogenic clones; 4 children carried one or more commensal clones and 2 children carried both uropathogenic and commensal clones.",
            "output": [
                "Are escherichia coli colonizing the neurogenic bladder similar to widespread clones causing disease in patients with normal bladder function?"
            ]
        },
        {
            "id": "task847-6b7c9835505a435690b2249ac99e8b5c",
            "input": "Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus).', 'To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN.', 'Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas 1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy.",
            "output": [
                "Does pTEN loss predict for response to RAD001 ( Everolimus ) in a glioblastoma orthotopic xenograft test panel?"
            ]
        },
        {
            "id": "task847-125c223f350840a6b8d76db419b68989",
            "input": "del(17p), del(11q), and associated p53 dysfunction predict for short survival and chemoresistance in B-cell chronic lymphocytic leukemia (CLL). DNA-dependent protein kinase (DNA-PK) is activated by DNA damage and mediates DNA double-strand break repair. We hypothesized that inhibiting DNA-PK would sensitize CLL cells to drug-induced DNA damage and that this approach could increase the therapeutic index of agents used to treat CLL.', 'Fifty-four CLL cases were characterized for poor prognosis markers [del(17p), del(11q), CD38, and ZAP-70]. In selected cases, DNA-PK catalytic subunit (DNA-PKcs) expression and activity and p53 function were also measured. Ex vivo viability assays established sensitivity to fludarabine and chlorambucil and also tested the ability of a novel DNA-PK inhibitor (NU7441) to sensitize CLL cells to these drugs. The effects of NU7441 on fludarabine-induced DNA damage repair were also assessed (Comet assays and detection of gammaH2AX).', 'DNA-PKcs levels correlated with DNA-PK activity and varied 50-fold between cases but were consistently higher in del(17p) (P = 0.01) and del(11q) cases. NU7441 sensitized CLL cells to chlorambucil and fludarabine, including cases with del(17p), del(11q), p53 dysfunction, or high levels of DNA-PKcs. NU7441 increased fludarabine-induced double-strand breaks and abrogated drug-induced autophosphorylation of DNA-PKcs at Ser2056. High DNA-PK levels predicted for reduced treatment-free interval.",
            "output": [
                "Is dNA-dependent protein kinase a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia?"
            ]
        },
        {
            "id": "task847-306ccfba73244d2e80222822cbc8722d",
            "input": "To examine changes in caries prevalence among 3 to 15-year-old adolescents.', 'Of 1582 eligible mothers, 1443 gave informed consent. Participating children and their parents were followed up continuously from 3 to 15 years of age in a pre-planned fashion and at regular intervals. Data on dental health status were obtained from 1066/1287 adolescents (82%) during regular clinical dental examinations.', 'Dentinal untreated caries (D) was seen among more than 26% of the adolescents at 15 years of age. Altogether, 4.9 carious teeth surfaces were affected in each case (mean). Close to 18% of the adolescents (186/1066) had poor dental health (DMFT was 5 or more) and 26% (271/1066) had DMFS 5 or more.",
            "output": [
                "Is childhood caries still in force : a 15-year follow-up?"
            ]
        },
        {
            "id": "task847-9d0f1288711b4d99896f122b6e76e27f",
            "input": "To investigate the effects of the Chinese herbal medicine of Longbixiao (LBX) Capsule on the expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro.', 'Blood serum medicated with LBX was incubated with the stromal cells isolated from men with benign prostatic hyperplasia (BPH) and cultured in vitro. The mRNA expression levels of TGF-beta1 and Smoothelin were detected by real-time RT-PCR and other relevant techniques.', 'In the high and low concentration groups, the gene relative expressions of TGF-beta1 were (0.158 +/- 0.020) and (0.169 +/- 0.020) , while those of Smoothelin were (0.035 +/- 0.007) and (0.036 +/- 0.007) respectively, both significantly decreased in comparison with the control group(P < 0.01).",
            "output": [
                "Does [ Longbixiao capsule reduce expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro ]?"
            ]
        },
        {
            "id": "task847-158b7c5434664135a9fafab45faddd74",
            "input": "IL-2 deficient (IL-2(-/-)) mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/-)-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis.', 'We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP) dendritic cells (DC). LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(lo)CD80(lo)MHC-II(hi)) whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR) 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/-)-mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/-)-DC in vitro.",
            "output": [
                "Does intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevent DC maturation and T-cell polarization?"
            ]
        },
        {
            "id": "task847-0b318fdbccf44d6ab6c9e373db3b6f20",
            "input": "Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na, K-ATPase and other ion transport proteins.', \"In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3',5 triiodo-L-thyronine (T(3)).\", 'AFC was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% bovine serum albumin solution with fluorescein-labeled albumin tracer and measuring the change in fluorescein isothiocyanate-albumin concentration over time.', \"Systemic treatment with intraperitoneal injections of T(3) for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T(3)-treated rats had higher Na, K-ATPase hydrolytic activity. T(3) (10(-6) M), but not reverse T(3) (3,3',5' triiodo-L-thyronine), applied to the alveolar space increased AFC by 31.8% within 1.5 hours. A 61.5% increase in AFC also occurred by airspace instillation of T(3) in ex vivo isolated lungs, suggesting a direct effect of T(3) on the alveolar epithelium. Exposure of rats to an oxygen concentration of greater than 95% for 60 hours increased wet-to-dry lung weights and decreased AFC, whereas the expression of thyroid receptor was not markedly changed. Airspace T(3) rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury.",
            "output": [
                "Does triiodo-L-thyronine rapidly stimulate alveolar fluid clearance in normal and hyperoxia-injured lungs?"
            ]
        },
        {
            "id": "task847-36009dda8dae493b943a5d8853025078",
            "input": "Small cell lung cancer (SCLC) is an aggressive malignancy. Current treatments yield dismal survival rates. We have previously demonstrated that histone deacetylase (HDAC) inhibitors can inhibit neuroendocrine tumor growth. Activation of the Notch1 signaling pathway also impairs SCLC cell viability. In this study, we investigated the ability of the HDAC inhibitor valproic acid (VPA) to activate Notch1 signaling and inhibit proliferation in SCLC cells.', 'DMS53 human SCLC cells were treated with VPA (0-10 mM) for 2 d. Light microscopy was used to examine changes in cell morphology. Western analysis was performed using antibodies against various Notch1 pathway proteins to assess Notch1 activation. Additionally, immunoblotting was performed for two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. Finally, a cell proliferation assay was used to measure the effects of VPA on SCLC growth over 8 d.', 'After treatment with VPA, DMS53 cells underwent dramatic changes in morphology. VPA induced expression of the full-length and active forms of Notch1 protein. Furthermore, VPA suppressed levels of neuroendocrine tumor markers chromogranin A and ASLC-1. Importantly, VPA treatment led to dose-dependent inhibition of SCLC cell proliferation.",
            "output": [
                "Does valproic acid induce Notch1 signaling in small cell lung cancer cells?"
            ]
        },
        {
            "id": "task847-b9158b59b0574a4284ed8b68c62bffe3",
            "input": "Ischemic preconditioning (IPC) mitigates ischemia-reperfusion (I/R) injury in experimental models. However, the clinical significance of this protection has been unclear and a mortality reduction has not been previously reported in noncardiac models. This study examined the local and remote protection afforded by skeletal muscle IPC and sought to determine the significance of this protection on mortality.', \"Mice subjected to 2 h hindlimb ischemia/24 h reperfusion (standard I/R injury) were compared with those undergoing a regimen of two 20-min cycles of IPC followed by standard I/R injury. Local injury was assessed via gastrocnemius histology, and remote injury was evaluated via intestinal histology and pulmonary neutrophil infiltration (n = 7). Mortality was compared in parallel groups for 1 week (n = 6). Groups were analyzed using an unpaired Student's t-test for gastrocnemius and pulmonary injury, and a Mann-Whitney rank sum test for intestinal injury. Mortality differences were interpreted through a hazard ratio.\", 'Significant protection was observed in preconditioned animals. There was a 35% local injury reduction in skeletal muscle (71.2% versus 46.0%, P < 0.01), a 50% reduction in remote intestinal injury (2.3 versus 1.1, P < 0.01), and a 43% reduction in remote pulmonary injury (14.9 versus 8.5, P < 0.01) compared with standard injury controls. Preconditioned animals were also significantly protected from mortality, demonstrating a 66.7% survival at 1 wk compared with 0% survival after standard injury alone (hazard ratio 0.20, 95% CI: 0.02-0.59).",
            "output": [
                "Does ischemic preconditioning of skeletal muscle mitigate remote injury and mortality?"
            ]
        },
        {
            "id": "task847-2cf9fac7de6d45979051995d04995a47",
            "input": "Caenorhabditis elegans chemosensation has been successfully studied using behavioral assays that treat detection of volatile and water soluble chemicals as separate senses, analogous to smell and taste. However, considerable ambiguity has been associated with the attractive properties of the compound ammonium-acetate (NH(4)Ac). NH(4)Ac has been used in behavioral assays both as a chemosensory neutral compound and as an attractant.', 'Here we show that over a range of concentrations NH(4)Ac can be detected both as a water soluble attractant and as an odorant, and that ammonia and acetic acid individually act as olfactory attractants. We use genetic analysis to show that NaCl and NH(4)Ac sensation are mediated by separate pathways and that ammonium sensation depends on the cyclic nucleotide gated ion channel TAX-2/TAX-4, but acetate sensation does not. Furthermore we show that sodium-acetate (NaAc) and ammonium-chloride (NH(4)Cl) are not detected as Na(+) and Cl(-) specific stimuli, respectively.",
            "output": [
                "Is ammonium-acetate sensed by gustatory and olfactory neurons in Caenorhabditis elegans?"
            ]
        },
        {
            "id": "task847-7178736412784dad9934b01e885a7f5b",
            "input": "Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4(+)CD25(+)FOXP3(+) T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs.', 'nTreg numbers and function were examined in a unique set of patients with type 1 diabetes who underwent rapamycin monotherapy before islet transplantation.', 'We found that rapamycin monotherapy did not alter the frequency and functional features, namely proliferation and cytokine production, of circulating nTregs. However, nTregs isolated from type 1 diabetic patients under rapamycin treatment had an increased capability to suppress proliferation of CD4(+)CD25(-) effector T-cells compared with that before treatment.",
            "output": [
                "Does rapamycin monotherapy in patients with type 1 diabetes modify CD4+CD25+FOXP3+ regulatory T-cells?"
            ]
        },
        {
            "id": "task847-2558a83b467149fd91eb9883e079d8f5",
            "input": "Mutations of p53 gene can contribute to the development of gastric cancer. Our aims were to evaluate the premalignant gastric intestinal metaplasia-related p53 alterations, using and comparing capillary sequencing and p53 resequencing chip in gastric biopsy and peripheral blood samples. Furthermore we examined the effect of p53 polymorphism on the protein expression level.', 'Deoxyribonucleic acid was extracted from antral gastric biopsy samples of 50 intestinal metaplasia patients (27 Helicobacter pylori positive, 23 H. pylori negative) and 51 controls (all H. pylori negative). Exon 4 of p53 gene was examined by capillary sequencing (CS). From 7 intestinal metaplasia patients extra deoxyribonucleic acid samples were extracted from blood and from the corpus and from the antrum of the stomach and 5 additional exons were examined by CS and 10 with GeneChip p53 Assay (Affymetrix). In 19 patients p53 immunohistochemistry was performed.', 'RR genotype on codon 72 was found to significantly (p=0.0087) reduce the chance of intestinal metaplasia in H. pylori positive patients as compared to the normal controls. The p53 alterations were identical in antral, corpus and blood samples. The p53 protein expression was in significant correlation with the genetic alterations. CS and chip method-based sequencing results were not in correlation.",
            "output": [
                "Does the RR genotype of codon 72 of p53 gene reduce the development of intestinal metaplasia?"
            ]
        },
        {
            "id": "task847-8d85ac3e16da4fe3a9ac371d08e7a73d",
            "input": "The purpose of this research study was to identify factors that are associated with receiving care in a medical home for children with special health care needs (CSHCN) and to identify how these factors vary among different socioeconomic levels.', 'Data were obtained from the National Survey of Children with Special Health Care Needs, 2000-2002. Access to a medical home was derived using an algorithm. This survey analysis also included demographic characteristics, geographical location of household, severity of condition, and social factors. Multiple logistic regression models were constructed for socioeconomic status (SES) levels defined by federal poverty level (FPL): <133%; 133-199%; 200-299%; > or =300%.', 'Age group was significant in all but the 200-299% of FPL stratum. Severity of condition was significant in all strata. Race was significant in all but the > or =300% stratum. Maternal education was borderline significant in the lowest and highest strata. Insurance type/status was significant in all but the 133-199% of FPL stratum. Geographical location was significant in the lowest and highest strata. The language of the interview was only significant in the lowest stratum. The relationship of the respondent to the child was significant in the middle two strata. The total number of adults in the household was significant in the highest stratum, and the total number of children in the household was significant in the 200-299% of FPL stratum.",
            "output": [
                "Do factors for accessing a medical home vary among CSHCN from different levels of socioeconomic status?"
            ]
        },
        {
            "id": "task847-92faa457113d46caa806f8c3649b75d6",
            "input": "The physiological basis of slow transit constipation (STC) in children remains poorly understood. We wished to examine pan-colonic motility in a group of children with severe chronic constipation refractory to conservative therapy.', 'We performed 24 h pan-colonic manometry in 18 children (13 boys, 11.6 +/- 0.9 yr, range 6.6-18.7 yr) with scintigraphically proven STC. A water-perfused, balloon tipped, 8-channel, silicone catheter with a 7.5 cm intersidehole distance was introduced through a previously formed appendicostomy. Comparison data were obtained from nasocolonic motility studies in 16 healthy young adult controls and per-appendicostomy motility studies in eight constipated children with anorectal retention and/or normal transit on scintigraphy (non-STC).', 'Antegrade propagating sequences (PS) were significantly less frequent (P < 0.01) in subjects with STC (29 +/- 4 per 24 h) compared to adult (53 +/- 4 per 24 h) and non-STC (70 +/- 14 per 24 h) subjects. High amplitude propagating sequences (HAPS) were of a normal frequency in STC subjects. Retrograde propagating sequences were significantly more frequent (P < 0.05) in non-STC subjects compared to STC and adult subjects. High amplitude retrograde propagating sequences were only identified in the STC and non-STC pediatric groups. The normal increase in motility index associated with waking and ingestion of a meal was absent in STC subjects.",
            "output": [
                "Does 24-Hour colonic manometry in pediatric slow transit constipation show significant reductions in antegrade propagation?"
            ]
        },
        {
            "id": "task847-d6b344d2bba04f0e9f82b88551dee078",
            "input": "Clinical predictors associated with acute paraquat (PQ) poisoning have not been systematically studied.', 'To identify independent predictors of death in patients with acute PQ poisoning.', 'This is a retrospective study executed in the emergency department of a university hospital. One hundred three consecutive patients poisoned with PQ between January 1999 and December 2004 were enrolled. Urine PQ concentration, electrolyte and renal function, detailed history, and Acute Physiology and Chronic Health Evaluation II were extracted from medical records. The outcome measure was 30-day mortality. Multivariate analysis was done by Cox-proportional hazard regression model. Receiver operating characteristics area under the curve was calculated for selected predictors.', 'The crude 30-day mortality was 67.9% (70 of 103). Independent predictors of death were acute renal failure (hazard ratio, 3.53; 95% confidence interval, 1.97-6.32), hypokalemia (2.07, 1.21-3.51), hypothermia (2.91, 1.67-5.07), suicide (2.11, 1.04-4.29), and self-reported ingested dose (2.06, 1.38-3.06). The receiver operating characteristics area under the curve of serum potassium concentrations, maximal urine PQ concentrations, and Acute Physiology and Chronic Health Evaluation II scores were 0.75 (95% confidence interval, 0.60-0.81), 0.71 (0.66-0.84), and 0.80 (0.71-0.88), respectively. Under the cutoff value of 3.6 mEq/L, hypokalemia had a sensitivity of 75% and specificity of 54% in predicting mortality.",
            "output": [
                "Are hypokalemia and hypothermia associated with 30-day mortality in patients with acute paraquat poisoning?"
            ]
        },
        {
            "id": "task847-ce2581e3a3774f638fe40b30dd00c406",
            "input": "Partial adherence to antihypertensive therapy remains a public health challenge and may be associated with increased cardiovascular risk. We quantitatively evaluated cardiovascular risk inherent in partial therapy adherence in spontaneously hypertensive rats with accelerated hypertension.', 'Adult spontaneously hypertensive rats were divided into 5 groups; Group 1 (controls) did not receive any treatment, whereas all other rats (Groups 2-5) were given nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) to exacerbate hypertension. Group 2 (untreated/nonadherers) was given L-NAME but not antihypertensive medication; Group 3 (Perfect Adherers) was treated daily with candesartan (10 mg/kg); Group 4 was given candesartan 3 times a week, whereas Group 5 received candesartan only during the last 6 days of the 3-week experiment (Partial Adherers). At the end, indices of systemic and regional (kidneys, brain, and heart) hemodynamics, and indices of left ventricular function were determined.', 'Treatment with L-NAME aggravated hypertension, adversely affected target organ blood flows and resistances, and grossly impaired ventricular function. Perfect adherence with candesartan completely reversed the adverse cardiovascular effects of L-NAME intervention. In partial adherers (Groups 4 and 5), arterial pressure decreased and reached control values. However, target organ hemodynamics and heart function showed only slight improvements, if any.",
            "output": [
                "Does partial adherence to antihypertensive therapy fail to achieve full cardiovascular benefits in hypertensive rats?"
            ]
        },
        {
            "id": "task847-3f241bd4fe6746b681ad10bbf9846e05",
            "input": "It has been speculated that invasive revascularization prevents development of cardiogenic shock. Data from randomised trials comparing angioplasty with fibrinolysis on the development of cardiogenic shock are lacking.', 'To elucidate the effect of angioplasty on in-hospital development of cardiogenic shock compared to fibrinolysis. To evaluate whether mortality in patients who develop cardiogenic shock after treatment is dependent on revascularization strategy.', 'DANAMI-2 randomly assigned 1572 STEMI patients to fibrinolysis (782 patients) or angioplasty (790 patients). Data on patients with in-hospital development of cardiogenic shock after randomisation were included. Of the 103 patients (6.6%) patients developing cardiogenic shock 57% were randomised to angioplasty with an unadjusted odds ratio of 1.39 (0.92-2.11, p=0.14). During the three year follow-up 58% of the total mortality was due to cardiogenic shock, and treatment strategy did not influence the risk associated with shock (hazard ratio of 1.05 (0.67-1.64) for angioplasty vs. fibrinolysis).",
            "output": [
                "Does percutaneous coronary intervention for acute MI prevent in-hospital development of cardiogenic shock compared to fibrinolysis?"
            ]
        },
        {
            "id": "task847-c05e9fb66ee94c0abbf6669f3f31e283",
            "input": "Cut-points (CP) for pain severity are useful because they may help clinicians to identify patients with clinically significant pain. However, a need exists to evaluate whether different pain severity groups differ on selected demographic, clinical, and pain characteristics, as well as on factors that may be amenable to psychoeducational interventions such as self-efficacy for pain management, coping strategies, and barriers to pain management. In this cross-sectional study of 210 oncology outpatients with pain, an optimal CP of 4 was found using ratings of average pain intensity. The variables that provided a unique contribution to the prediction of membership in the >4 CP group were gender, presence of breakthrough pain, comorbidities, barriers to pain management, and total self-efficacy for pain management. In addition, patients in the >4 CP group reported lower scores on physical, role, cognitive, and global health function.",
            "output": [
                "Are demographic , clinical , and pain characteristics associated with average pain severity groups in a sample of oncology outpatients?"
            ]
        },
        {
            "id": "task847-5495f398ece64c03bddf7eb4becad9e4",
            "input": "Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial upper airway obstruction by decreasing skeletal upper airway muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on upper airway integrity and breathing are unknown.', 'Fifty-one adult male rats were anaesthetized with isoflurane, tracheostomized, and a femoral artery and vein were cannulated. First, we compared the efficacy of sugammadex 15 mg kg(-1) and neostigmine 0.06 mg kg(-1) to reverse respiratory effects of rocuronium-induced partial paralysis [train-of-four ratio (T4/T1)=0.5]. Subsequently, we compared the safety of sugammadex and neostigmine given after recovery of the T4/T1 to 1, by measuring phasic genioglossus activity and breathing.', 'During partial paralysis (T4/T1=0.5), time to recovery of minute volume to baseline values was 10.9 (2), 75.8 (18), and 153 (54) s with sugammadex, neostigmine, and placebo, respectively (sugammadex was significantly faster than neostigmine and placebo, P<0.05). Recovery of T4/T1 was also faster for sugammadex than neostigmine and placebo. Neostigmine administration after complete recovery of T4/T1 decreased upper airway dilator muscle activity to 64 (30)% of baseline and decreased tidal volume (P<0.05 for both variables), whereas sugammadex had no effect on either variable.",
            "output": [
                "Does neostigmine but not sugammadex impair upper airway dilator muscle activity and breathing?"
            ]
        },
        {
            "id": "task847-b8ea037552964034afc797069792a0ab",
            "input": "Type 1 diabetes mellitus (DM) is an autoimmune disorder with disturbed glucose/insulin metabolism, which has no medical treatment other than life-long insulin therapy, despite which 30% of subjects develop organ failure. Herein we have reported the use of human adipose-tissue-derived, insulin-making mesenchymal stem cells (h-AD-MSC) transfused with unfractionated cultured bone marrow (CBM) in 5 insulinopenic DM patients.', \"Five (M:F, 2:3) insulinopenic DM patients of 0.6 to 10 years' duration, ages 14 to 28 years under treatment insulin (Human with 14-70 U/d) showed postprandial blood sugars between 156 to 470 mg%, glycosylated hemoglobin 6.8% to 9.9% and c-peptide levels of 0.02 to 0.2 ng/mL. They underwent intraportal administration of xenogeneic-free h-AD-MSC (mean dose = 1.5 mL; cell counts, 2.1 x 10(3)/muL). The CD45-/90+/73(+) cells (29.8/16.8%) showed c-peptide levels of 3.08 ng/mL, insulin level of 1578 micro IU/mL. The aliquot was supplemented with CBM (mean dose 94 mL with cell counts: 18.7 x 10(3)/microL) containing CD45-/34+ elements of 0.93%. The Institutional Review Board approved the study protocol and consent forms.\", 'All patients were successfully infused CBM plus h-AD-MSC without any untoward effects and showed 30% to 50% decreased insulin requirements with 4- to 26-fold increased serum c-peptide levels, with a mean follow-up of 2.9 months.",
            "output": [
                "Do human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin?"
            ]
        },
        {
            "id": "task847-972d66a16d3e46c69a4fe06eba773a7b",
            "input": "To evaluate various formats for the communication of prenatal test results.', 'In study 1 (N=400), female students completed a questionnaire assessing risk perception, affect, and perceived usefulness of prenatal test results. A randomized, 2 (risk level; low, high) x 4 (format; ratio with numerator 1, ratio with denominator 1000, Paling Perspective Scale, pictograms) design was used. Study 2 (N=200) employed a 2 (risk level; low, high) x 2 (format; Paling Perspective Scale, risk comparisons in numerical format) design.', 'In study 1, the Paling Perspective Scale resulted in a higher level of perceived risk across different risk levels compared with the other formats. Furthermore, participants in the low-risk group perceived the test results as less risky compared with participants in the high-risk group (P < 0.001) when the Paling Perspective Scale was used. No significant differences between low and high risks were observed for the other 3 formats. In study 2, the Paling Perspective Scale evoked higher levels of perceived risks relative to the numerical presentation of risk comparisons. For both formats, we found that participants confronted with a high risk perceived test results as more risky compared with participants confronted with a low risk.",
            "output": [
                "Does the effect of graphical and numerical presentation of hypothetical prenatal diagnosis result on risk perception?"
            ]
        },
        {
            "id": "task847-58c0cda07fef4bc09e6affbab8b1609c",
            "input": "The activation of Ras signaling and vascular endothelial growth factor (VEGF) expression in mesangial cells is a pathogenic consequence of diabetic nephropathy. We examined the role of simvastatin in modulating Ras signaling and the expression of VEGF in mesangial cells stressed with high doses of glucose in vitro and in vivo.', 'For the in vitro studies, we cultured mesangial cells, with or without simvastatin or manumycin A pretreatment, in 35 mM glucose and assayed VEGF activity. For the in vivo studies, we administered simvastatin or manumycin A to streptozocin-induced diabetic rats for 28 days and dissected renal tissues for an immunohistological assessment of Ras and VEGF expression in glomerular cells.', \"We showed that high glucose significantly increased VEGF gene expression and Ras activation. The pretreatment with 10 microM simvastatin and inhibition of Ras activity by manumycin A significantly reversed high glucose promotion of VEGF mRNA expression. Pretreatment with simvastatin and manumycin A clearly affected the activation of Ras promoted by high glucose. Tube-like formations were abundant in high glucose-treated mesangial cells co-cultured with HUVEC. However, the simvastatin and manumycin A treatment group's down-regulated tube formation was comparable to the mesangial cells treated only with high glucose. Exogenous simvastatin and manumycin A treatment alleviated urinary albumin secretion and attenuated Ras activation and VEGF protein expression in the kidneys of diabetic rats.",
            "output": [
                "Does simvastatin alleviate diabetes-induced VEGF-mediated nephropathy via the modulation of Ras signaling pathway?"
            ]
        },
        {
            "id": "task847-662dfb44d48b47409fb23cf8c71dfecd",
            "input": "The aim was to examine the role of trait anxiety and diagnosis on depressive symptoms and fatigue in women with early stage breast cancer or benign breast problems.', 'A prospective follow-up study was performed in order to find predictors of depressive symptoms and fatigue.', 'From the 169 participating women, 81 patients had breast cancer and 88 benign breast problems. Questionnaires for depressive symptoms and fatigue were completed before diagnosis (T1) and 1 (T2), 3 (T3), and 6 (T4) months after diagnosis (benign patients) or surgical treatment (breast cancer patients). A trait anxiety questionnaire was only completed before diagnosis was known.', 'Trait anxiety, assessed before diagnosis, was the only significant predictor of depressive symptoms at T4, even when depressive symptoms at baseline was included in the analysis. Fatigue at T4 was predicted by fatigue at baseline and trait anxiety. Demographic characteristics, diagnosis (benign or breast cancer) and adjuvant treatment (chemotherapy, radiotherapy, hormone therapy) did not play a role. Patients with breast cancer or benign breast problems scoring high on trait anxiety, scored higher on depressive symptoms and fatigue than the other patients, at all time points.",
            "output": [
                "Does trait anxiety determine depressive symptoms and fatigue in women with an abnormality in the breast?"
            ]
        },
        {
            "id": "task847-dc380d03916c46dc8f6cbe655044faf5",
            "input": "Anti-Mullerian hormone (AMH) may have a role in disordered folliculogenesis in polycystic ovary syndrome (PCOS). Though there have been several investigations into circulating AMH levels in patients with PCOS, no previous studies have compared AMH concentrations in the follicular fluid of unstimulated ovaries in women with PCOS with that of normally ovulating women.', 'Follicular fluid was aspirated from 4-8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS (n = 11) and those with regular ovulatory cycles (n = 8). Follicular AMH was compared in the two groups. Serum samples were analysed for AMH and endocrine profile.', 'Follicular fluid AMH levels were significantly higher (P < 0.0001) in women with anovulatory PCOS (median: 466.2 ng/ml) compared with normal-ovulatory controls (median: 78.0 ng/ml). Mean follicular fluid AMH levels in PCOS patients were 60 times higher than in the serum. Moreover, there was a significant correlation between the follicular fluid and serum concentrations of AMH in the PCOS group (r = 0.86; P = 0.007) but not in controls.",
            "output": [
                "Is anti-Mullerian hormone increased in follicular fluid from unstimulated ovaries in women with polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-26fb736404824e06afaccfb46ac26692",
            "input": "The protein tyrosine kinase focal adhesion kinase (FAK) and Src in association with phosphorylation of the adapter protein paxillin are essential in tumor metastasis formation. Elevated levels of FAK, Src and paxillin may increase the metastatic potential of colorectal tumor cells. The aim of the current study was to examine the expression of FAK, Src, and paxillin using immunohistochemistry in the context of disease progression and to evaluate its clinical significance as a prognostic factor.', 'The relationship between FAK, Src and paxillin levels and colorectal cancer progression was evaluated by immunohistochemistry in 104 colorectal cancer specimens with clinical follow up. In addition, FAK, Src and paxillin expression levels were quantified in 68 colorectal tumors and corresponding liver metastases.', 'FAK and paxillin expression individually did not significantly impact time to recurrence (p=0.09, and p=0.89 respectively). Src expression was associated with tumor recurrence p=0.03. However, tumors that expressed both high FAK and Src levels had a significant shorter time to recurrence (p=0.004, hazard ratio: 2.98, 95% CI 1.14-6.31). FAK, Src and paxillin showed equivalent levels in corresponding liver metastases compared to the primary tumors (p=0.67, p=0.28 and p=0.34 respectively).",
            "output": [
                "Is combined expression of the non-receptor protein tyrosine kinases FAK and Src in primary colorectal cancer associated with tumor recurrence and metastasis formation?"
            ]
        },
        {
            "id": "task847-fc38a7efc7954e1db898623a70da3564",
            "input": "Programmed cell death (apoptosis) has been implicated in tumor development and may affect the metastatic potential of tumor cells. The role of bcl-2, a proto-oncogene that inhibits apoptosis, has been studied in several malignancies, including cutaneous melanoma (CM). The purpose of this study was to evaluate the immunohistochemical expression of bcl-2 in 35 regional lymph node, 28 subcutaneous and 17 visceral CM metastases, correlating the findings with patient survival.', 'In a historical cohort study patient survival was correlated with the expression of bcl-2 in regional lymph node, subcutaneous and visceral metastases of CM. Eighty slides containing surgical specimens from 50 patients diagnosed with stage III and IV CM, 28 male (56%) and 22 female (44%), were analyzed. Mean age at diagnosis was 43 years (16-74 years; median = 42 years). Mean Breslow depth was 5.01 mm (0.4-27.5 mm). The slides were submitted to immunohistochemical reaction using anti-bcl-2 monoclonal antibody and classified according to the degree of staining (< 5%; 5 to 50%; or > 50% of tumor cells stained). The relationship between bcl-2 protein expression and survival for each type of metastasis, gender and age at initial diagnosis was analyzed.', 'Mean overall survival was 33.9 months after the diagnosis of the initial metastatic lesion (range: 0 to 131 months). Twenty-four out of 50 patients (48%) had died from CM by the end of the study period. bcl-2 expression was detected in 74.3, 85.7 and 82.4% of lymph node, subcutaneous and visceral metastases, respectively. After univariate and multivariate analyses, no correlation was found between positive bcl-2 expression and overall survival for the types of metastases evaluated.",
            "output": [
                "Is bcl-2 expression associated with survival in metastatic cutaneous melanoma : a historical cohort study?"
            ]
        },
        {
            "id": "task847-c861b57346af4a279acb7602189813f2",
            "input": "The efficacy of continuing medical education in anesthesiology has been examined very little. This study compared the efficacy of a lecture on air embolism to that of a class that used a problem/case-based learning approach.', \"Prospective, randomized study enrolling 52 experienced anesthesiologists participating in a professional development course. Twenty-six anesthesiologists attended a lecture on air embolism in anesthesia and 25 attended a problem-based class. The objectives were the same for both groups and had been defined previously. The participants' knowledge was evaluated before and after the instruction with tests based on 2 cases dealing with the same knowledge areas: risk factors and symptoms, diagnosis, monitoring, and treatment.\", 'No significant between-group differences were found for any of the knowledge areas before or after the classes. After instruction, participants who listened to the lecture improved their scores for knowledge of monitoring (P = .03) and treatment (P = .001). Participants in the problem-based learning group also improved their scores for knowledge of treatment (P = .003).",
            "output": [
                "Does [ Problem/case-based learning compared to lecture for acquiring knowledge of air embolism in continuing medical education ]?"
            ]
        },
        {
            "id": "task847-e3add088760e4835bc62fc85b20e2891",
            "input": "Cognitive inhibition processes were found to be deficient early in the clinical course of Alzheimer's disease (AD). The inhibition of redundant information is a precondition for efficient cognitive processing and presumably modulated by prefrontal attentional networks. Deficits in the suppression of the evoked potential P50 response to paired clicks are well known in schizophrenic patients and undergo cholinergic modulation. In this study, we aimed to investigate inhibitory gating deficits of P50 in AD and their relation to neuropsychological measures.\", 'P50 suppression was assessed in 19 AD-patients in comparison to a young and elderly control group (n=17 each) and related to MMSE and specific neuropsychological assessments.', 'Patients showed reduced sensory gating compared to healthy elderly (p<0.021) and exhibited significantly higher N40-P50-amplitudes. There were no age or gender effects in controls. Frontal neuropsychological tests (TMT-B, verbal fluency) and working memory requiring inhibition, but not declarative memory functions, were significantly correlated with inhibitory gating and test amplitude in both, AD-patients and controls.",
            "output": [
                "Does p50 gating deficit in Alzheimer dementia correlate to frontal neuropsychological function?"
            ]
        },
        {
            "id": "task847-2f8844b6cc19493f8e182e8473074443",
            "input": "Pathogenic mycobacteria such as M. tuberculosis, M. bovis or M. leprae are characterised by their extremely slow growth rate which plays an important role in mycobacterial virulence and eradication of the bacteria. Various limiting factors influence the generation time of mycobacteria, and the mycobacterial DNA-binding protein 1 (MDP1) has also been implicated in growth regulation. Our strategy to investigate the role of MDP1 in mycobacterial growth consisted in the generation and characterisation of a M. bovis BCG derivative expressing a MDP1-antisense gene.', 'The expression rate of the MDP1 protein in the recombinant M. bovis BCG containing the MDP1-antisense plasmid was reduced by about 50% compared to the reference strain M. bovis BCG containing the empty vector. In comparison to this reference strain, the recombinant M. bovis BCG grew faster in broth culture and reached higher cell masses in stationary phase. Likewise its intracellular growth in mouse and human macrophages was ameliorated. Bacterial clumping in broth culture was reduced by the antisense plasmid. The antisense plasmid increased the susceptibility of the bacteria towards Ampicillin. 2-D protein gels of bacteria maintained under oxygen-poor conditions demonstrated a reduction in the number and the intensity of many protein spots in the antisense strain compared to the reference strain.",
            "output": [
                "Does the mycobacterial DNA-binding protein 1 ( MDP1 ) from Mycobacterium bovis BCG influence various growth characteristics?"
            ]
        },
        {
            "id": "task847-08f7b1cf0d044b91ac6d2a2501770192",
            "input": "Recently we reported that fluid shear stress promotes endothelial cell differentiation from a mouse embryo mesenchymal progenitor cell line C3H10T1/2. However, it is not clear whether the transforming growth factor-beta 1 (TGF-beta1) system is associated with shear-induced endothelial differentiation. The purpose of this study was to determine the effect of shear stress on the expression of TGF-beta1 and its signaling molecules in C3H10T1/2 cells.', 'Murine C3H10T1/2 cells were incubated on collagen Type 1-coated dishes, and subjected to a steady fluid shear stress of 15 dyn/cm(2) for 6, 12, and 24 h. The mRNA levels for TGF-beta1, TGF-beta receptors (TGF-beta R), and Smad molecules were determined with real-time PCR analysis and normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels.', 'TGF-beta1 mRNA expression was down-regulated by 60% and 66% in shear stress-treated cells at 12 and 24 h, respectively, compared with static control group (P < 0.01). In addition, shear stress significantly decreased TGF-beta R1 mRNA levels by 30% and 50% in shear stress-treated cells at 12 and 24 h, respectively (P < 0.01). For TGF-beta R2, shear stress at 6, 12, and 24 h significantly reduced its expression by 93%, 95% and 97%, respectively, compared with static controls (P < 0.01). Furthermore, shear stress significant decreased mRNA levels of positive signaling molecules Smad2, Smad3, and Smad4 in a time-dependent manner (P < 0.01). However, shear stress significantly increased negative signaling molecule Smad7 mRNA levels by 100% at 24 h treatment compared with static control group (P < 0.01).",
            "output": [
                "Does fluid shear stress regulate the expression of TGF-beta1 and its signaling molecules in mouse embryo mesenchymal progenitor cells?"
            ]
        },
        {
            "id": "task847-1dd29845a3a948f9b661e023cdf6419a",
            "input": "Efavirenz is used for the antiretroviral treatment of HIV/tuberculosis-coinfected patients in developing countries. A switch to nevirapine is regularly carried out because of the cost and side effects of efavirenz. Pharmacokinetic studies suggested that nevirapine should be initiated at full dose when used as a substitute for efavirenz.', 'The aim of this study was to measure the cumulative incidence of adverse events (AEs) related to nevirapine in patients switched from efavirenz to immediate full-dose nevirapine (FDN).', 'In 2001 an antiretroviral treatment programme was initiated with the first-line regimen stavudine, lamivudine and efavirenz. In 2003, the fixed-dose combination of stavudine, lamivudine and nevirapine was recommended. Thus, first-line therapy was changed and FDN was initiated when patients were switched from efavirenz to nevirapine.', 'Between April and December 2004, 394 patients were switched from efavirenz to FDN. The cumulative incidence of AEs related to nevirapine was 13.2% [95% confidence interval (CI) 10.2-16.7] and that of severe AEs was 8.9% (95% CI 6.5-11.9). In women the incidence of AEs was 17.6% (95% CI 12.1-24.3) and that of severe AEs was 12.2% (95% CI 7.7-18.2).",
            "output": [
                "Is efavirenz replacement by immediate full-dose nevirapine safe in HIV-1-infected patients in Cambodia?"
            ]
        },
        {
            "id": "task847-928825e05e6840969a097cabb449ec81",
            "input": "To test the hypothesis that a novel phase-contrast optical coherence tomography (OCT) system can image retinal and choroidal vessels in the living mouse.', 'A high-speed spectral domain optical coherence tomography (SDOCT) system, which measures the reflections for the entire depth of the retina at once with each axial scan (A-scan), was developed for mouse retinal imaging. Acquiring multiple A-scans over a transverse line across the mouse retina offers a two-dimensional cross-sectional image (B-scan); several neighboring B-scans can be assembled into a three-dimensional OCT image. To visualize mobility and transverse flow in retinal vessels, the statistical variance of phase for each location was calculated from multiple B-scans acquired successively for the same retinal cross-section. Such measures of phase variance offer a direct measure of motions over a large dynamic range of flow velocities.', 'Three-dimensional phase-contrast images of the live mouse retina were created using multiple two-dimensional cross-sectional image slices through the retina. For the data presented here, each cross-sectional phase-contrast slice resulted from five images of 100 or 200 transverse pixels, acquired over 25 ms or 50 ms, respectively. The approach offered clear identification of motion regions at different depths, including flow in the retinal microvasculature and in the choroidal vessels.",
            "output": [
                "Does phase-contrast OCT imaging of transverse flow in the mouse retina and choroid?"
            ]
        },
        {
            "id": "task847-ecf05f2e5f3c4739a6a08a6bbfa4a9d0",
            "input": "We aim to find what is the relationship between B cell antibody responses and specific T cell help in the specific cases of allergy and tolerance to peanuts.', 'B cell antibody responses to foreign proteins usually depend upon antigen-specific T cell help. However, specific antibody levels can sometimes be maintained lifelong after infections or vaccination.', 'We measured peanut-specific proliferation and antibody levels in peanut-allergic and non-allergic children using tritiated thymidine incorporation and UniCAP, respectively. We also investigated the corresponding tetanus toxoid specific responses in both groups.', \"We found that tetanus-specific IgG did not correlate with lymphocyte proliferation (Spearman rank correlation coefficient r'=0.08, P=0.74) nor with tetanus-specific cytokine production (IFN-gamma: r'=0.198, P=0.285; TNF-alpha: r'=0.274, P=0.146; IL-4: r'=-0.007, P=0.96; P=0.221; IL-13: r'=0.363, P=0.056). Conversely, in peanut-allergic donors, peanut-specific IgE (average 21 kU/L, median 2.27 kU/L, range 0.34-100 kU/L) but not peanut-specific IgG was positively correlated with proliferation (r'=0.751, P=0.003). In these donors, specific IgE was positively correlated with peanut-specific Th2 cytokines production: r'=0.635, P=0.02 for IL-4 and r'=0.641, P=0.025 for IL-13 and negatively correlated with Th1 cytokines (r'=-0.71, P=0.007 for IFN-gamma and r'=-0.746, P=0.005 for TNF-alpha, respectively). However, peanut-specific IgE was not correlated with T cell proliferation or cytokine production in non-allergic individuals. In conclusion, in allergic individuals, B and T cell responses to peanut antigens are correlated whereas normal immune responses B and T cell responses are uncoupled.",
            "output": [
                "Are peanut-specific B and T cell responses correlated in peanut-allergic but not in non-allergic individuals?"
            ]
        },
        {
            "id": "task847-9c0bbf2ea72441ee8e6deac8551382da",
            "input": "Estimated glomerular filtration rate (eGFR) before coronary artery bypass graft (CABG) surgery is a key risk factor of in-hospital mortality. However, in patients with normal renal function before CABG, acute kidney injury develops after the procedure, making postoperative renal function assessment necessary for evaluation. Postoperative eGFR and its association with long-term survival have not been well studied.', 'We studied 13,593 consecutive CABG patients in northern New England from 2001 to 2006. Patients with preoperative dialysis were excluded. Data were linked to the Social Security Association Death Master File to assess long-term survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by established categories of postoperative eGFR (90 or greater, 60 to 89, 30 to 59, 15 to 29, and less than 15 mL x min(-1) x 1.73 m(-2)).', 'Median follow-up was 2.8 years (mean, 2.7; range, 0 to 5.5). Patients with moderate to severe acute kidney injury (less than 60) after CABG had significantly worse survival than patients with little or no acute kidney injury (90 or greater).",
            "output": [
                "Is long-term survival after cardiac surgery predicted by estimated glomerular filtration rate?"
            ]
        },
        {
            "id": "task847-8878c54f736144b2a2c459d68714509a",
            "input": "During early to late-fetal liver development, bipotential hepatoblasts proliferate and differentiate into hepatocytes and cholangiocytes. The prospero-related homeobox 1 gene (Prox1) is expressed in hepatoblasts, and the inactivation of Prox1 causes defective early liver development, in particular, faulty migration of fetal hepatoblasts. Prox1 binds to another hepatocyte-enriched transcription factor, liver receptor homolog 1 (Lrh1), and suppresses its transcriptional activity. However, the molecular mechanism by which Prox1 and Lrh1 regulate the characteristics of fetal hepatic cells remains unknown. We investigated the contribution of Prox1 and Lrh1 in early liver development. Embryonic day 13 liver-derived CD45-Ter119-Dlk+ cells were purified as fetal hepatic stem/progenitor cells, and formation of colonies derived from single cells was detected under low-density culture conditions. We found that overexpression of Prox1 using retrovirus infection induced migration and proliferation of fetal hepatic stem/progenitor cells. In contrast, overexpression of Lrh1 suppressed colony formation. Prox1 induced the long-term proliferation of fetal hepatic stem/progenitor cells, which exhibited both high proliferative activity and bipotency for differentiation. Prox1 up-regulated expression of cyclins D2, E1, and E2, whereas it suppressed expression of p16(ink4a), the cdk inhibitor. In addition, overexpression of Prox1 significantly inhibited the proximal promoter activity of p16(ink4a).",
            "output": [
                "Do prospero-related homeobox 1 and liver receptor homolog 1 coordinately regulate long-term proliferation of murine fetal hepatoblasts?"
            ]
        },
        {
            "id": "task847-f9c9dc3fdf8f4f6bb0adcfc8e1d68283",
            "input": "High throughput screens with RNA interference technology enable loss-of-function analyses of gene activities in mammalian cells. While the construction of genome-scale shRNA libraries has been successful, results of large-scale screening of those libraries can be difficult to analyze because of the relatively high noise levels and the fact that not all shRNAs in a library are equally effective in silencing gene expression.', 'We have screened a library consisting of 43,828 shRNAs directed against 8,500 human genes for functions that are necessary in cell detachment induced by a constitutively activated c-Abl tyrosine kinase. To deal with the issues of noise and uncertainty of knockdown efficiencies, we employed an analytical strategy that combines quantitative data analysis with biological knowledge, i.e. Gene Ontology and pathway information, to increase the power of the RNAi screening technique. Using this strategy we found 16 candidate genes to be involved in Abl-induced disruption of cell adhesion, and verified that the knockdown of IL6ST is associated with enhanced cell attachment.",
            "output": [
                "Does systems analysis of quantitative shRNA-library screens identify regulators of cell adhesion?"
            ]
        },
        {
            "id": "task847-1db7cb6f97c947888dcff17fbc485d4d",
            "input": "The aim was to review different approaches for the derivation of threshold values and to discuss their strengths and limitations in the context of minimum provider volumes.', \"The following methods for the calculation of threshold values are compared and discussed: The value of acceptable risk limit, the value of acceptable risk gradient, the benchmark value proposed by Budtz-J\u00f8rgensen and Ulm's breakpoint model. The latter is extended to account for two different breakpoints. The methods are applied to German quality assurance data concerning total knee replacement.\", 'The discussed methods for calculating threshold values differ in the kind of information that has to be specified beforehand. For the value of acceptable risk limit approach an absolute number, the acceptable risk, has to be predetermined. The value of acceptable risk gradient approach and the method of Budtz-J\u00f8rgensen require the specification of a relative change expressed in gradient and in odds, respectively. On the other hand, the threshold value according to the method of Ulm is defined as a parameter of a statistical model and no a priori specification is required.",
            "output": [
                "Are flexible regression models useful tools to calculate and assess threshold values in the context of minimum provider volumes?"
            ]
        },
        {
            "id": "task847-00f82687a58d44348a96aa065fa285e7",
            "input": "Total blood homocysteine (Hcys) and folate levels have been investigated in association with cognitive dysfunction in healthy but not in multimorbid elderly patients. We hypothesized that total serum Hcys is an adequate marker to identify multimorbid elderly patients with cognitive dysfunction assessed by the Short Cognitive Performance Test (SKT) and Mini-Mental State Examination (MMSE).', 'Cross-sectional study.', 'The study center was an acute geriatric hospital.', 'A total of 189 multimorbid elderly patients were recruited.', 'Cognitive dysfunction was determined according to the SKT and MMSE. Biochemical parameters (Hcys, folate, vitamin B12, hemoglobin), nutritional status (BMI, Mini Nutritional Assessment, nutritional intake), and activities of daily living were assessed.', 'According to the SKT, 25.4% of patients showed no cerebral cognitive dysfunction, 21.2% had suspected incipient cognitive dysfunction, 12.7% showed mild cognitive dysfunction, 9.0% had moderate cognitive dysfunction, and 31.7% of patients were demented. The median plasma Hcys value was elevated by approximately 20% in multimorbid elderly patients, independent of cognitive dysfunction. Serum folate and vitamin B12 concentrations were within normal ranges. We did not find significant differences in nutritional status, activities of daily living, numbers of diseases or medications, or selected biochemical parameters between the SKT groups.",
            "output": [
                "Do total serum homocysteine levels identify cognitive dysfunction in multimorbid elderly patients?"
            ]
        },
        {
            "id": "task847-4d21fbc1861d414a95f2034c5e35ea2e",
            "input": "Adipocytes express inflammatory mediators that contribute to the low-level, chronic inflammation found in obese subjects and have been linked to the onset of cardiovascular disorders and insulin resistance associated with type 2 diabetes mellitus. A reduction in inflammatory gene expression in adipocytes would be expected to reverse this low-level, inflammatory state and improve cardiovascular function and insulin sensitivity. The natural products, curcumin and resveratrol, are established anti-inflammatory compounds that mediate their effects by inhibiting activation of NF-kappaB signaling. In the present study, we examined if these natural products can inhibit NF-kappaB activation in adipocytes and in doing so reduce cytokine expression.', 'Cytokine (TNF-alpha, IL-1beta, IL-6) and COX-2 gene expression in 3T3-L1-derived adipocytes was measured by quantitative real-time PCR (qRT-PCR) with or without TNFalpha-stimulation. Cytokine protein and prostaglandin E2 (PGE2) expression were measured by ELISA. Effects of curcumin and resveratrol were evaluated by treating TNFalpha-stimulated adipocytes with each compound and 1) assessing the activation state of the NF-kappaB signaling pathway and 2) measuring inflammatory gene expression by qRT-PCR and ELISA.', 'Both preadipocytes and differentiated adipocytes express the genes for TNF-alpha, IL-6, and COX-2, key mediators of the inflammatory response. Preadipocytes were also found to express IL-1beta; however, IL-1beta expression was absent in differentiated adipocytes. TNF-alpha treatment activated NF-kappaB signaling in differentiated adipocytes by inducing IkappaB degradation and NF-kappaB translocation to the nucleus, and as a result increased IL-6 (6-fold) and COX-2 (2.5-fold) mRNA levels. TNF-alpha also activated IL-1beta gene expression in differentiated adipocytes, but had no effect on endogenous TNF-alpha mRNA levels. No detectable TNFalpha or IL-1beta was secreted by adipocytes. Curcumin and resveratrol treatment inhibited NF-kappaB activation and resulted in a reduction of TNF-alpha, IL-1beta, IL-6, and COX-2 gene expression (IC50 = 2 muM) and a reduction of secreted IL-6 and PGE2 (IC50 ~ 20 muM).",
            "output": [
                "Do curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes?"
            ]
        },
        {
            "id": "task847-964444bf2b90448eb2ecd302ef86fed2",
            "input": "The perinucleolar compartment (PNC) is a subnuclear structure localized at the nucleolar periphery. Previous studies using breast cancer as a model system demonstrated that PNC prevalence (the percentage of cells with 1 or more PNC) increased with disease progression and was associated with poor patient outcomes.', 'To evaluate the validity of developing PNC prevalence as a novel pancancer prognostic marker, the authors investigated whether PNC prevalence was correlated with malignancy in a spectrum of tissue types and evaluated its selective association with malignancy under various experimental conditions.', 'PNC prevalence was low in primary and immortalized cells and in cell lines derived from hematologic malignancies, but it was heterogeneous in cell lines derived from solid tumors, including those of epithelial and nonepithelial origins. Studies using human myometrial tissue and thyroid cancer cell lines with various levels of malignancy demonstrated a correlation between high PNC prevalence and malignant potential. Furthermore, PNC prevalence corresponded directly to metastatic capacities in a series of well characterized cell lines of the same origin that were selected for various levels of metastatic capacity in a mouse model. Conversely, PNC prevalence was reduced experimentally by over expressing an antimetastatic protein in breast cancer cells. However, PNC prevalence was not associated with traits that were shared by both cancer and normal cells, including proliferation, glycolysis, and differentiation.",
            "output": [
                "Is perinucleolar compartment prevalence a phenotypic pancancer marker of malignancy?"
            ]
        },
        {
            "id": "task847-fb3f5e166e1646ebb0e2d8e683b1209a",
            "input": "In atherogenesis, dendritic cells, beside presenting antigens, may be sources of tumour necrosis factor (TNF)alpha and nitric oxide (NO), together with mast cells and smooth muscle cells.', 'We have looked at the expression of TNFalpha and inducible NO synthase (iNOs) by these cells by affinity cytochemistry in autoptical specimens from normal carotid arteries and not ruptured, hemorrhagic or calcified atheromata.', 'Round to dendritic, major histocompatibility complex class II molecules (MHC-II+) cells and avidin-labeled mast cells were rare in normal arteries and significantly more numerous in atheromata. Many MHC-II+ cells expressed S-100 antigen; while a few were positive for phalloidin; appreciable fractions of these cells were immunoreactive for TNFalpha and iNOs, both in control specimens and atheromata. The fraction of mast cells labeled for iNOs was significantly lower in atheromata than in controls. Phalloidin positive cells were the most abundant cell type in the normal intima and atheromata; the fractions of these cells labeled for TNFalpha and iNOs were significantly higher in atheromata than in controls. Very few of these cells were also labeled for MHC-II. Computerized image analysis confirmed that the amounts of iNOs and TNFalpha were higher in atheromata than in controls. The increase in TNFalpha in atheromata was also confirmed by western blot.",
            "output": [
                "Are smooth muscle cells , dendritic cells and mast cells sources of TNFalpha and nitric oxide in human carotid artery atherosclerosis?"
            ]
        },
        {
            "id": "task847-2992748e8f4442178d1a2fbc32525b9b",
            "input": "SNP309 polymorphism (T-G) at the promoter region of MDM2 has been reported to cause increased binding affinity of transcriptional activator Sp1 followed by increased MDM2 both in mRNA and protein level. This model was proposed in vitro in the small panel of cell lines that indicated an on average 8-fold higher level of MDM2 mRNA in cells bearing the GG genotype.', 'The incidence of SNP309 was determined in a cohort of 158 breast, 17 endometrium, 13 cervix and 45 ovarian cancer tissues by PCR-RFLP. The expression of p53 and MDM2 protein levels in the cohort was immunohistochemically investigated and statistically correlated with SNP309 polymorphism using Pearson chi(2) and t test.', 'No significant difference was observed in the G allele incidence in breast cancer specimens compared to 149 noncancer controls. Furthermore, no statistically significant association of the G allele frequencies and p53 and MDM2 protein expression levels was observed.",
            "output": [
                "Does mDM2SNP309 associate with elevated MDM2 protein expression or breast cancer risk?"
            ]
        },
        {
            "id": "task847-90d1ac26971c44169ccaacc43926b501",
            "input": "Urinary dysfunction (UD) is common after rectal cancer treatment, but the contribution of each treatment component (surgery and radiotherapy) to its development remains unclear. This study aimed to evaluate UD during 5 years after total mesorectal excision (TME) and to investigate the influence of preoperative radiotherapy (PRT) and surgical factors.', 'Patients with operable rectal cancer were randomized to TME with or without PRT. Questionnaires concerning UD were completed by 785 patients before and at several time points after surgery. Possible risk factors, including PRT, demographics, tumour location, and type and extent of resection, were investigated by multivariable regression analysis.', 'Long-term incontinence was reported by 38.1 per cent of patients, of whom 72.0 per cent had normal preoperative function. Preoperative incontinence (relative risk (RR) 2.75, P = 0.001) and female sex (RR 2.77, P < 0.001) were independent risk factors. Long-term difficulty in bladder emptying was reported by 30.6 per cent of patients, of whom 65.0 per cent had normal preoperative function. Preoperative difficulty in bladder emptying (RR 2.94, P < 0.001), peroperative blood loss (RR 1.73, P = 0.028) and autonomic nerve damage (RR 2.82, P = 0.024) were independent risk factors. PRT was not associated with UD.",
            "output": [
                "Is urinary dysfunction after rectal cancer treatment mainly caused by surgery?"
            ]
        },
        {
            "id": "task847-48180c062f2d44e59b671053405cdfa6",
            "input": "Mesalazine has been identified as a candidate chemopreventive agent in colon cancer prophylaxis because of its pro-apoptotic and anti-proliferative effects. However, the precise mechanisms of action are not entirely understood. The aim of our study was to investigate the involvement of peroxisome proliferator-activated receptor gamma (PPARgamma) in mesalazine's anticarcinogenic actions in colorectal cancer cells.\", 'The effects of mesalazine on cell cycle distribution, cell count, proliferation and caspase-mediated apoptosis were examined in Caco-2, HT-29 and HCT-116 cells used as wild-type, dominant-negative PPARgamma mutant and empty vector cultures. We focused on caspase-3 activity, cleavage of poly(ADP-ribose) polymerase (PARP), caspase-8 and caspase-9, as well as on expression of survivin, X-linked inhibitor of apoptosis (Xiap), phosphatase and tensin homolog deleted from chromosome ten (PTEN) and c-Myc. Techniques employed included transfection assays, immunoblotting, flow cytometry analysis, colorimetric and fluorometric assays.', 'Mesalazine caused a time- and dose-dependent decrease in both cell growth and proliferation. Growth inhibition was accompanied by a G1/G0 arrest, a significant increase in PTEN, caspase-3 activity, cleavage of PARP and caspase-8, whereas the expressions of Xiap, survivin and c-Myc were decreased simultaneously. Cleavage of caspase-9 was not observed. Moreover, PPARgamma expression and activity were elevated. The growth-inhibitory effect of mesalazine was partially reduced in dominant-negative PPARgamma mutant cells, whereas the expression of c-Myc was not affected. Mesalazine-mediated increased caspase-3 activity, the expression of PTEN, cleavage of PARP and caspase-8 as well as reduced levels of survivin and Xiap were completely abolished in the PPARgamma mutant cell lines.",
            "output": [
                "Is pPARgamma involved in mesalazine-mediated induction of apoptosis and inhibition of cell growth in colon cancer cells?"
            ]
        },
        {
            "id": "task847-4dcec5090d9e41ebbf2c32ed9eda0860",
            "input": "Major depression (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive amygdala activity and under-recruitment of dorsolateral prefrontal cortex (DLPFC). The purpose of this study was to examine the effects of antidepressant treatment on anomalous neural activity in cognitive-control and emotion-processing circuitry.', 'Functional magnetic resonance imaging was conducted on depressed patients (n=23) (both before and after antidepressant treatment) compared with matched controls (n=18) while they performed a cognitive task involving attended and unattended fear-related stimuli.', 'After eight weeks of SSRI antidepressant treatment, patients with depression showed significantly increased DLPFC activity to unattended fear-related stimuli and no longer differed from controls in either DLPFC or amygdala activity.",
            "output": [
                "Does antidepressant treatment normalize hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression?"
            ]
        },
        {
            "id": "task847-36435e008352433facbe4ba97a7c51ef",
            "input": "Mesenchymal stem/progenitor cells (MSCs) are multipotent progenitors that differentiate into such lineages as bone, fat, cartilage and stromal cells that support haemopoiesis. Bone marrow MSCs can also contribute to cardiac repair, although the mechanism for this is unclear. Here, we examine the potential of MSCs from different sources to generate cardiomyocytes in vitro, as a means for predicting their therapeutic potential after myocardial infarction.', \"Mesenchymal stem/progenitor cells were isolated from the perivascular tissue and Wharton's jelly of the umbilical cord and from cord blood. Their immunophenotype and differentiation potential to generate osteoblasts, chondrocytes, adipocytes and cardiomyoxcytes in vitro was compared with those of bone marrow MSCs.\", 'Mesenchymal stem/progenitor cells isolated from umbilical cord and cord blood were phenotypically similar to bone marrow MSCs, the exception being in the expression of CD106, which was absent on umbilical cord MSCs, and CD146 that was highly expressed in cord blood MSCs. They have variable abilities to give rise to osteoblasts, chondrocytes and adipocytes, with bone marrow MSCs being the most robust. While a small proportion (approximately 0.07%) of bone marrow MSCs could generate cardiomyocyte-like cells in vitro, those from umbilical cord and cord blood did not express cardiac markers either spontaneously or after treatment with 5-azacytidine.",
            "output": [
                "Do 5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord , cord blood and bone marrow generate cardiomyocytes in vitro at high frequencies?"
            ]
        },
        {
            "id": "task847-2316dfc175f44f15a32632c68fe707ee",
            "input": "Precooling has been shown to enhance performance in repeated sprint exercise in able-bodied subjects in a hot environment. Spinal cord injury causes thermoregulatory impairment with a detrimental effect on performance. This study assessed whether cooling strategies before and during exercise in the heat enhances sprint performance in athletes with tetraplegia.', 'Eight male athletes with tetraplegia performed intermittent arm crank exercise in the heat (32.0 degrees C (0.1 degrees C); humidity, 50% (0.1%)) for a maximum of 60 min or until exhaustion. Trials involved a no-cooling control (CON), precooling (PRE) or cooling during exercise (DUR). Each intermittent sprint protocol consisted of varied periods of passive rest, maximal sprinting and active recovery.', 'Both PRE and DUR cooling strategies improved the ability of the athletes to repeatedly perform high-intensity sprints, with times to exhaustion (TTE), whereas during the CON trial, athletes demonstrated a reduction in the total number of sprints and TTE (47.2 (10.8), 52.8 (5.8) and 36.2 (9.6) min for CON, PRE and DUR, respectively). Core temperature was significantly higher for CON (37.3 degrees C (0.3 degrees C)) when compared with both PRE and DUR (36.5 degrees C (0.6 degrees C) and 37.0 degrees C (0.5 degrees C), respectively, p<0.01). Ratings of perceived exertion and thermal sensation upon exhaustion or completion were not different.",
            "output": [
                "Do cooling strategies improve intermittent sprint performance in the heat of athletes with tetraplegia?"
            ]
        },
        {
            "id": "task847-924083e7640c448cb865d37b648f00d7",
            "input": "The therapeutic importance of immune responses against single versus multiple antigens is poorly understood. There also remains insufficient understanding whether responses to one subset of antigens are more significant than another. Autoantibodies are frequent in cancer patients. They can pose no biological significance or lead to debilitating paraneoplastic syndromes. Autoreactivity has been associated with clinical benefits, but the magnitude necessary for meaningful results is unknown. Autologous tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor generate immune infiltrates in preexisting metastases with associated tumor destruction. We sought to identify targets of responses from this vaccination strategy.', 'Postvaccination sera used in screening a cDNA expression library prepared from a densely infiltrated metastasis of a long-term surviving melanoma patient identified several autoantigens. Additional autoantigens were identified through similar screenings in non-small cell lung cancer and murine models, and proteins implicated in cancer propagation. ELISAs for several targets were established using recombinant proteins, whereas others were evaluated by petit serologies.', 'Eleven gene products were identified through serologic screening from two patients showing highly favorable clinical outcomes. A subset of antigens revealed significant changes in antibody titers compared with weak responses to other proteins. Time course analyses showed coordinated enhanced titers against several targets as a function of vaccination in responding patients.",
            "output": [
                "Are concerted potent humoral immune responses to autoantigens associated with tumor destruction and favorable clinical outcomes without autoimmunity?"
            ]
        },
        {
            "id": "task847-142204d8dc444cd7ba48dce759d9b8a2",
            "input": "Platelet concentrates are important for support of patients with malignancies requiring myelotoxic chemotherapy. During storage, 10% to 15% of platelets may become activated resulting in the release of alpha-granules, which contain growth factors. We hypothesize that, during storage, growth factors accumulate in the plasma, specifically platelet-derived growth factor, vascular endothelial growth factor (VEGF), transforming growth factor-beta, and fibroblast growth factor-2, which may adversely affect cancer patients.', 'The concentrations of growth factors were measured by ELISA from the plasma of apheresis platelets serially throughout storage (days 1, 3, 5, and 7) and compared with concentrations in fresh plasma from healthy blood donors. Washing was evaluated as a method of growth factor removal, and an in vitro model of platelet transfusion in a patient receiving Bevacizumab (Avastin) using immunoprecipitation was employed to determine if Bevacizumab would be bound by the VEGF in apheresis platelets.', 'VEGF, platelet-derived growth factor, and transforming growth factor-beta were increased on day 1 versus fresh plasma and throughout storage reaching a relative maximum at outdate (P < 0.01, day 5 or 7). Fibroblast growth factor-2 concentrations were significantly increased on day 7 alone versus day 1 or to fresh plasma (P < 0.01). Washing removed 41 +/- 11% to 56 +/- 2% of the growth factors. Bevacizumab effectively bound the VEGF from apheresis platelets, with significant amounts of VEGF remaining in the supernatant.",
            "output": [
                "Do oncogenic and angiogenic growth factors accumulate during routine storage of apheresis platelet concentrates?"
            ]
        },
        {
            "id": "task847-09a5b62e26634f4b8c44d8b398668eda",
            "input": "Evaluate the codelivery of hyaluronidase enzyme with oncolytic adenoviruses to determine whether it improves the spread of the virus throughout tumors, thereby leading to a greater overall antitumor efficacy in tumor models.', 'The optimal dose of hyaluronidase that provided best transduction efficiency and spread of a green fluorescent protein (GFP)-expressing adenovirus within tumors was combined with oncolytic viruses in tumor models to determine whether the combination treatment results in an improvement of antitumor efficacy.', 'In mice injected with the adenovirus Ad5/35GFP and an optimal dose of hyaluronidase (50 U), a significant increase in the number of GFP-expressing cells was observed when compared with animals injected with virus only (P < 0.0001). When the oncolytic adenoviruses Ad5OV or Ad5/35 OV (OV-5 or OV5T35H) were codelivered with 50 U of hyaluronidase, a significant delay in tumor progression was observed, which translated into a significant increase in the mean survival time of tumor-bearing mice compared with either of the monotherapy-treated groups (P < 0.0001). Furthermore, the mice that received the combination of Ad5/35 OV and hyaluronidase showed the best antitumor efficacy. Importantly, the combination treatment did not increase the metastatic potential of the tumors. Lastly, the increase in virus potency observed in animals injected with both enzyme and virus correlated with enhanced virus spread throughout tumors.",
            "output": [
                "Does intratumoral coadministration of hyaluronidase enzyme and oncolytic adenoviruses enhance virus potency in metastatic tumor models?"
            ]
        },
        {
            "id": "task847-d6f9042cea3440f79fcbaca2c23a1c6d",
            "input": "Our previously reported therapeutic synergy between naturally occurring seleno-amino acid methylselenocysteine (MSC) and anticancer drugs could not be shown in vitro. Studies were carried out to investigate the potential role of MSC-induced tumor vascular maturation and increased drug delivery in the observed therapeutic synergy in vivo.', 'Mice bearing s.c. FaDu human head and neck squamous cell carcinoma xenografts were treated with MSC (0.2 mg/d x 14 days orally). Changes in microvessel density (CD31), vascular maturation (CD31/alpha-smooth muscle actin), perfusion (Hoechst 33342/DiOC7), and permeability (dynamic contrast-enhanced magnetic resonance imaging) were determined at the end of the 14-day treatment period. Additionally, the effect of MSC on drug delivery was investigated by determining intratumoral concentration of doxorubicin using high-performance liquid chromatography and fluorescence microscopy.', 'Double immunostaining of tumor sections revealed a marked reduction ( approximately 40%) in microvessel density accompanying tumor growth inhibition following MSC treatment along with a concomitant increase in the vascular maturation index ( approximately 30% > control) indicative of increased pericyte coverage of microvessels. Hoechst 33342/DiOC7 staining showed improved vessel functionality, and dynamic contrast-enhanced magnetic resonance imaging using the intravascular contrast agent, albumin-GdDTPA, revealed a significant reduction in vascular permeability following MSC treatment. Consistent with these observations, a 4-fold increase in intratumoral doxorubicin levels was observed with MSC pretreatment compared with administration of doxorubicin alone.",
            "output": [
                "Does tumor vascular maturation and improved drug delivery induced by methylselenocysteine lead to therapeutic synergy with anticancer drugs?"
            ]
        },
        {
            "id": "task847-1db5d3488202472e86310410490abef9",
            "input": "Electroporation has been shown to increase the efficacy of intramuscular injection of plasmid DNA, resulting in a higher level of foreign gene expression. Using this technique, we examined the effect of viral IL-10 gene transfer on the prevention of tracheal allograft stenosis in an animal model.', 'On the day of tracheal transplantation, recipient Lewis rats were intramuscularly injected with either plasmid pCAGGS-LacZ or plasmid pCAGGS-viral IL-10, followed immediately by electroporation. Tracheas from Brown Norway donors were transplanted into the backs of Lewis recipients, and the histology of the grafts were assessed 2 and 4 weeks after transplantation.', 'The serum level of IL-10 peaked at 2000 pg/ml one day after injection; the level then slowly decreased, but was maintained above 1000 pg/ml until 8 days after injection. At Day 28, the airway lumina of the tracheal allografts were almost completely obliterated by fibroproliferative tissue in the control pCAGGS-LacZ-treated rats. In rats injected once with pCAGGS-viral IL-10, luminal obliteration was significantly decreased compared with the control pCAGGS-LacZ-treated rats (mean luminal opening 46.8% vs 0% p<0.05). The loss of epithelial cells lining the airway was also decreased in the IL-10-treated group (mean epithelial coverage 42% vs 5% p<0.05). Multiple injections with pCAGGS-viral IL-10 did not further improve the histological changes.",
            "output": [
                "Does electroporation-mediated transfer of plasmid DNA encoding IL-10 attenuate orthotopic tracheal allograft stenosis in rats?"
            ]
        },
        {
            "id": "task847-dc2241924135450ca81ec2881dd1ae6d",
            "input": "There is growing evidence that hypertensive pregnancy complications and other adverse pregnancy outcomes are associated with the presence of inherited or acquired thrombophilias. As hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is one of the most severe forms of pre-eclampsia we aimed to assess the prevalence of the factor V Leiden, the prothrombin 20210G >A mutation and the methylenetetrahydrofolate reductase (MTHFR) 677C >T polymorphism in women with HELLP syndrome and in their fetuses from the same index pregnancy.', 'The study was performed retrospectively in a case-control design.', 'Seventy-one mother-child pairs with HELLP syndrome and 79 control mother-child pairs with uncomplicated pregnancies were included in the study.', 'Genotyping of the three thrombophilic mutations was performed using the LightCycler technology. The chi-squared test was used for statistical analysis. Main outcome measures were maternal and fetal genotypes and their correlation with clinical parameters.', 'Maternal heterozygosity for factor V Leiden was significantly more prevalent in the HELLP group than in controls (OR 4.45, 95% CI 1.31-15.31). No significant association was observed for maternal prothrombin mutation or MTHFR polymorphism (p=0.894, p=0.189, respectively). The fetal genotype was not associated with HELLP syndrome for any of the three mutations investigated. Analysis of gene-gene interactions and genotype-phenotype correlation with respect to clinical parameters and perinatal outcome revealed no further differences.",
            "output": [
                "Is maternal factor V Leiden mutation associated with HELLP syndrome in Caucasian women?"
            ]
        },
        {
            "id": "task847-530b966de4e5432fbada8ed43c48af06",
            "input": "To compare silica gel with acyclovir cream in the treatment of recurrent herpes labialis.', 'In this randomized, open-label, comparator-controlled trial, 74 patients with recurrent herpes labialis applied silica gel or acyclovir cream respectively over a period of 10 days. The treatment started within 24 hours of the first symptoms of a new recurrence. Patients rated five symptoms (tautness, tingling, itching, burning sensation, pain), lesion stage, efficacy, tolerability, and duration until the onset of improvement. Their willingness-to-pay was assessed. Physicians rated the severity of the herpes recurrence and efficacy.', \"There was no significant difference between silica gel and acyclovir cream in the overall patients' assessment. There is evidence that silica gel relieved all investigated symptoms earlier than acyclovir cream. The efficacy and tolerability of both medications were rated as good to very good.",
            "output": [
                "Is silica gel as effective as acyclovir cream in patients with recurrent herpes labialis : results of a randomized , open-label trial?"
            ]
        },
        {
            "id": "task847-5163f2e1e18240759470b3bb9144c957",
            "input": "We compared conventional treatment with pumpless extracorporeal lung membrane (Interventional Lung Assist [iLA] Novalung; Novalung GmbH, Hechingen, Germany) support in a pig model of postpneumonectomy severe acute respiratory distress syndrome.', 'Adult pigs underwent a left thoracotomy without (group I) or with a left extrapericardial pneumonectomy and radical lymphadenectomy (groups II to V). After stabilization, pigs belonging to group II were observed only, whereas in those belonging to groups III to V, a surfactant-depletion severe (Pao(2)/Fio(2) < 100) postpneumonectomy acute respiratory distress syndrome was induced. This was followed by observation (group III); treatment with conventional therapy including protective ventilation, steroids, and nitric oxide (group IV); or femoral arteriovenous iLA Novalung placement, near-static ventilation, steroids, and nitric oxide (group V). Each group included 5 animals. Primary outcome was extubation 12 hours postoperatively or postpneumonectomy acute respiratory distress syndrome.', 'A severe postpneumonectomy acute respiratory distress syndrome was obtained after 9 +/- 2 alveolar lavages over 90 +/- 20 minutes. In group V pigs, the iLA Novalung device diverted 17% +/- 4% of the cardiac output, permitted an oxygen transfer and carbon dioxide removal of 298.4 +/- 173.7 mL/min and 287.7 +/- 87.3 mL/min, respectively, and static ventilation (tidal volume, 2.2 +/- 1 mL/kg; respiratory rate, 6 +/- 2.9 breaths/min). All but 1 pig belonging to group V could be extubated compared with none in groups III and IV (P < .01), and only their lungs normalized cytokine release (P < .001) and surfactant (P < .03) and displayed fewer parenchymal lesions (P < .05).",
            "output": [
                "Does extracorporeal lung membrane provide better lung protection than conventional treatment for severe postpneumonectomy noncardiogenic acute respiratory distress syndrome?"
            ]
        },
        {
            "id": "task847-ad3034863cb84678be3d019953130df9",
            "input": "Accurate prediction of recovery of dysfunctional myocardium would optimize risk/benefit analysis among patients with coronary artery disease and decreased ventricular function. Tissue-tagged magnetic resonance imaging permits quantitative assessment of changes in ventricular function and may improve the prediction of myocardial recovery after coronary artery bypass grafting.', 'Thirteen patients underwent preoperative and postoperative stress magnetic resonance imaging with strain analysis at rest with 5 and 10 microg x kg(-1) x min(-1) dobutamine. Two-dimensional strain analysis was performed on a single midventricular short-axis image divided into 6 regions for each patient (n = 78). Regional minimum principal, circumferential, and radial strain values were calculated at each stress level. Regional changes in postoperative strain were correlated with changes in preoperative dobutamine stress by means of logistic regression. Receiver operating characteristic curves were created to determine the accuracy of preoperative dobutamine stress for the prediction of postoperative myocardial recoverability.', 'Minimum principal, circumferential, and radial strain values at 5 and 10 microg of dobutamine differed significantly from baseline strains (P < .05). Receiver operator characteristic curves found minimum principal strain to be 75% accurate for prediction of recoverability at both stress levels. Circumferential strain was 72% and 70% accurate at 5 and 10 microg, respectively, whereas radial strain was 77% and 64% accurate at 5 and 10 microg, respectively.",
            "output": [
                "Does low-dose dobutamine cardiac magnetic resonance imaging with myocardial strain analysis predict myocardial recoverability after coronary artery bypass grafting?"
            ]
        },
        {
            "id": "task847-f4325fc0e8bd4e10a0058c098b0650fa",
            "input": "Persistent neutrophil influx into the airways is a characteristic of chronic respiratory infection and contributes to the deterioration of pulmonary function. Ghrelin is a novel growth hormone (GH)-releasing peptide with potential anti-inflammatory activities. The present study investigated whether or not ghrelin can reduce neutrophil-dominant inflammation in airways of patients with chronic respiratory infection.', \"Synthesized ghrelin was administered intravenously for 3 weeks to 7 cachectic patients with chronic respiratory infection to confirm ghrelin's effects on airway inflammation and nutrition state. Neutrophils, neutrophil products and inflammatory cytokines in sputum were used as markers of airway inflammation. Changes in serum protein levels were also evaluated along with plasma catecholamine levels. Exercise tolerance was assessed by measuring 6-min walking distance before and after 3 weeks of ghrelin treatment.\", 'Three-week ghrelin administration decreased neutrophil density and inflammatory cytokine levels in sputum, reduced plasma norepinephrine level, and increased body weight, serum protein level, and 6-min walking distance.",
            "output": [
                "Does ghrelin treatment suppress neutrophil-dominant inflammation in airways of patients with chronic respiratory infection?"
            ]
        },
        {
            "id": "task847-9cc5f3ff21324065b25b78d2e025ffca",
            "input": "The lowest peak expiratory flow (PEF) over a week, expressed as a percentage of the highest PEF (Min%Max PEF) has been reported to be the index that most closely correlates with airway hyperresponsiveness (AHR) in asthmatics. However, both fluctuation of the airway caliber and airflow limitation are regarded as physiological properties of asthma closely related to AHR. An accurate index that shows the degree of AHR may be obtained by combining the index of airway lability with the parameters that represent airway caliber.', 'Ninety-two steroid-naive and twenty-eight steroid-treated asthmatic patients were enrolled. Using the physiological parameters obtained from spirometry and PEF monitoring, we investigated the indices which correlate accurately with airway responsiveness measured by the inhalation challenge test.', 'Although the methacholine threshold was related to all parameters that represent airway caliber and lability, Min%Max PEF had the strongest correlation with AHR. When Min%Max PEF was adjusted by the airway geometric factors, the normalization of Min%Max PEF with forced expiratory volume in one second as a percentage of the predicted value (%FEV(1)) improved the relationship between Min%Max PEF and AHR.",
            "output": [
                "Is peak expiratory flow variability adjusted by forced expiratory volume in one second a good index for airway responsiveness in asthmatics?"
            ]
        },
        {
            "id": "task847-99a94151f3f14ba0b13dd0b538108918",
            "input": "The present paper examines the relationship between social factors, food consumption during television viewing, and overall television viewing and how these are associated with BMI when the role of familial and social factors are considered in a population-based birth cohort of pre-school children from Qu\u00e9bec (Canada).', \"The analyses were performed using data from the Longitudinal Study of Child Development in Qu\u00e9bec (1998-2002) (LSCDQ). The study follows a representative sample (n 2103) of children born in 1998 in the Canadian province of Qu\u00e9bec. A nutrition assessment was conducted on 1549 children aged 4.5 years and included a 24 h dietary recall, an eating behaviour and television viewing questionnaire, and a measurement of children's heights and weights. Statistical analyses were performed.\", 'Nearly one-quarter of children ate at least twice daily in front of the television. Children who consumed snacks while watching television on a daily basis had higher BMI than children who did so less frequently. Children who ate snacks in front of the television every day, or some times during the week, ate more carbohydrates (total), more fat and less protein, fewer fruits and vegetables, and drank soft drinks more often than children who never ate snacks in front of the television.",
            "output": [
                "Is social factors and television use during meals and snacks associated with higher BMI among pre-school children?"
            ]
        },
        {
            "id": "task847-9585971bfcc3418c8103d4d967b76cb8",
            "input": "To analyze cell viability and morphology of primary cell cultures from CD133 immunolabeled and sorted cells from epithelium of patients suffering from benign prostate hyperplasia (BPH).', 'Cells obtained from 5 patients were divided in two fractions. First fraction (CD133+/CD133-) was cultivated in DMEM with 10% FBS. Second fraction was mixed with CD133 microbeads and immunomagnetically divided into CD133+ and CD133- fractions. These cells were cultivated and followed-up for 2 weeks. Cells were stained for Annexin V FITC/propidium iodide.', 'Seventy CD133+/CD133- cultures, thirty-one of CD133+ and thirty-one of CD133- cells were established. There were 5-fold and 3-fold increase of CD133+/CD133- and CD133+ cell number after 2 weeks, respectively. CD133+/CD133- and CD133+ monolayers displayed epithelial-like morphology and cytokeratine expression. CD133- cultures collapsed. Cell viability within CD133+ and CD133- populations was 90.1-/+6.3% and 24.3-/+6.2%, respectively. Apoptotic index was 9.0-/+6.1% and 28.5-/+23.8% within CD133+ and CD133- cultures, respectively.",
            "output": [
                "Are progenitor cells responsible for formation of human prostate epithelium primary cultures?"
            ]
        },
        {
            "id": "task847-66ba5e9d4d444e01919759ae255749bb",
            "input": "Pathological evidence supports a potential role of the pro- and anti-inflammatory cytokine network in the pathogenesis of inflammatory bowel disease (IBD). Moreover, associated studies suggest a possible involvement of cytokine-related genes in IBD susceptibility. In this study, we evaluated the effect of the anti-inflammatory interleukin-10 (IL10) gene on ulcerative colitis (UC).', 'Two functional single nucleotide polymorphisms (-1082 G/A, -819 T/C) in the IL10 promoter in 203 Italian sporadic UC patients and 391 controls were determined using high-resolution melting analysis.', 'The frequency of the -1082A allele was significantly higher in the UC patients than in controls (p=0.00003); -1082 genotype frequencies were also significantly different between UC patients and controls (p=0.0001). Allele and genotype frequencies of -819 T/C were not significantly associated with UC. Furthermore, the frequencies of haplotypes -1082A/-819C and -1082A/-819T, which have been reported to have a lower promoter activity, were significantly higher in UC patients than in controls (p=0.0004). After gender stratification, we found a significant difference in the -1082A allele (p=0.00004) and genotype (p=0.0002) frequencies only between female UC patients and controls; the same result was obtained for the -1082A/-819C and -1082A/-819T haplotypes (p=0.0006).",
            "output": [
                "Do interleukin-10 promoter polymorphisms influence susceptibility to ulcerative colitis in a gender-specific manner?"
            ]
        },
        {
            "id": "task847-ad01f56e4083407abfdcb2dbd4b3a25d",
            "input": "To determine the antiviral activity of phosphorodiamidate morpholino oligomers (PMO) and peptide-conjugated PMO (PPMO) in AG129 mice infected with dengue 2 virus (DENV-2).', \"Antisense PMO and PPMO were designed against the 5' terminal region (5'SL) or the 3'-cyclization sequence region (3'CS) of DENV genomic RNA and administered to AG129 mice before and/or after infection with DENV-2. In addition, cell culture evaluations designed to determine optimum PPMO length, and pharmacokinetic and toxicity analysis of PPMO were also carried out.\", \"Mock-treated AG129 mice lived for 9-17 days following intraperitoneal (ip) infection with 10(4)-10(6) pfu of DENV-2 (strain New Guinea C). Intraperitoneal administration of 5'SL or 3'CS PPMO before and after DENV infection produced an increase in the average survival time of up to 8 days. Animals receiving only post-infection PPMO treatment did not benefit significantly. Cell culture studies showed that PPMO of 22-24 bases long produced substantially higher DENV titre reductions than did PPMO that were either shorter or longer. Pharmacokinetic and toxicology analysis with non-infected animals showed that nine consecutive once-daily ip treatments of 10 mg/kg PPMO resulted in high concentrations of PPMO in the liver and caused little impact on overall health.",
            "output": [
                "Does treatment of AG129 mice with antisense morpholino oligomers increase survival time following challenge with dengue 2 virus?"
            ]
        },
        {
            "id": "task847-31497ffa42c24a93baebcc6e313b499d",
            "input": "To investigate the effect of recurrent laryngeal nerve (RLN) identification on the complications after total thyroidectomy and lobectomy.', 'Total 134 consecutive patients undergoing total thyroidectomy or thyroid lobectomy from January 2003 to November 2004 were investigated retrospectively. Patients were divided into two groups: RLN identified (Group A) or not (Group B). The two groups were compared for RLN injury and hypocalcaemia.', 'The numbers of patients and nerves at risk were 71 and 129 in Group A, and 63 and 121 in Group B, respectively. RLN injury in Group A (0) was significantly lower than that in Group B (5 [7.9%]) patients, 7 [5.8%] nerves) for the numbers of patients (P=0.016) and nerves at risk (P=0.006). Temporary hypocalcaemia was significantly higher in Group A than in Group B (14 [24.1%] vs 6 [10.3%], P=0.049). Permanent complications in Group B were significantly higher than those in Group A (13 [20.6%] vs 4 [5.6%], P=0.009).",
            "output": [
                "Is total thyroidectomy safer with identification of recurrent laryngeal nerve?"
            ]
        },
        {
            "id": "task847-7197ede450b34eec860b10945923b513",
            "input": "The association between epilepsy and autism is consistently reported, with a wide range of prevalence rates. This may be attributed to the heterogeneity of the samples with respect to age, comorbidity, sex, and intellectual disability (ID). We aimed to compare the prevalence of epilepsy 1) among autistic patients with ID versus autistic patients without ID and 2) among male versus female autistic patients.', 'We reviewed all data available from published reports (1963-2006) on autism and epilepsy and conducted a meta-analysis of 10 and 14 studies, respectively, to assess the relative risk (RR) of epilepsy in autism according to ID and gender. The pooled groups included 2112 (627 with IQ > or = 70, 1485 with IQ < 70) and 1530 (1191 male, 339 female) patients, respectively.', 'There was a strong discrepancy in relative risk (RR) according to IQ, with more autistic patients with ID having epilepsy (RR = .555; 95% confidence interval [CI]: .42-.73; p < .001). The pooled prevalence of epilepsy was 21.5% in autistic subjects with ID versus 8% in autistic subjects without ID. There was a strong discrepancy in RR according to sex, favoring comorbidity of epilepsy in autistic girls (RR = .549; 95% CI: .45-.66; p < .001). The male:female ratio of autism comorbid with epilepsy was close to 2:1 whereas the male:female ratio of autism without epilepsy was 3.5:1.",
            "output": [
                "Is epilepsy in autism associated with intellectual disability and gender : evidence from a meta-analysis?"
            ]
        },
        {
            "id": "task847-3534bfdffe854d3e849f055629ccef2e",
            "input": "To analyze the functional connectivity patterns of the different EEG bands during wakefulness and sleep (different sleep stages and cyclic alternating pattern (CAP) conditions), using concepts derived from Graph Theory.', 'We evaluated spatial patterns of EEG band synchronization between all possible pairs of electrodes (19) placed over the scalp of 10 sleeping healthy young normal subjects using two graph theoretical measures: the clustering coefficient (Cp) and the characteristic path length (Lp). The measures were obtained during wakefulness and the different sleep stages/CAP conditions from the real EEG connectivity networks and randomized control (surrogate) networks (Cp-s and Lp-s).', 'We found values of Cp and Lp compatible with a small-world network organization in all sleep stages and for all EEG bands. All bands below 15Hz showed an increase of these features during sleep (and during CAP-A phases in particular), compared to wakefulness.",
            "output": [
                "Does the functional connectivity of different EEG bands move towards small-world network organization during sleep?"
            ]
        },
        {
            "id": "task847-68d479238f044d49b87b3518241f39f6",
            "input": "Several mechanisms have been proposed as possible causes of transfusion-related immunomodulation (TRIM) after allogeneic transfusion. If one of these mechanisms, the release of mediators of immunity and inflammation (\"biologic response modifiers\"[BRMs]) from disintegrating blood cells during storage of blood products, really causes TRIM, it should in principle also occur after autologous transfusion. As a consequence, prestorage leukoreduction of autologous blood should be able to prevent the clinical consequences of TRIM after autologous transfusion.', 'This hypothesis was investigated in a multicenter, double-blind, randomized controlled trial. A total of 1089 patients scheduled for total hip arthroplasty and eligible for preoperative autologous blood donation were randomly assigned to receive autologous whole blood (AWB) either unmodified or leukoreduced when transfusion was indicated.', 'Neither the primary study outcome, that is, the overall postoperative infection rate (17.3% vs. 17.6%, p = 0.59), nor several secondary outcomes like median length of hospital stay (14 days vs. 14 days, p = 0.17) were significantly different between groups, whether analyzed according to the intention-to-treat principle or \"as treated.\"",
            "output": [
                "Does leukodepletion of autologous whole blood have no impact on perioperative infection rate and length of hospital stay?"
            ]
        },
        {
            "id": "task847-6a793ec413624e33be49665e087276b6",
            "input": "Factors influencing alloimmunization to transfused red blood cells (RBCs) are not well understood. Utilizing a murine model, we have recently reported that RBC alloimmunization is enhanced by recipient treatment with viral-like polyinosinic polycytidylic acid (poly(I:C)). To determine whether a different subtype of inflammation also enhances RBC alloimmunization, we investigated the effects of the bacterial endotoxin lipopolysaccharide (LPS) on alloimmunization.', 'Mice were treated with poly(I:C) or LPS; in select experiments, the precursor frequency of na\u00efve antigen-specific CD4+ T cells was increased using T cells from T-cell receptor transgenic mice. Recipients were transfused with leukoreduced RBCs expressing the membrane-bound hen egg lysozyme (mHEL) antigen, and alloimmunization was measured by anti-HEL immunoglobulin G responses using enzyme-linked immunosorbent assay and flow cytometric cross-match. Costimulatory molecule expression was examined on antigen-presenting cells (APCs) by flow cytometry.', 'Increased expression of costimulatory molecules on APCs was seen after treatment with either poly(I:C) and LPS. In contrast to the enhancement of RBC alloimmunization observed after treatment with poly(I:C), LPS not only failed to enhance but also actively suppressed alloimmunization, even in the presence of increased mHEL-specific CD4+ T cells (p < 0.001 LPS vs. control).",
            "output": [
                "Do discrete Toll-like receptor agonists have differential effects on alloimmunization to transfused red blood cells?"
            ]
        },
        {
            "id": "task847-484641440dc34e6081eb4d36a7cb4b41",
            "input": "Ionizing-radiation-resistant bacteria (IRRB) show a surprising capacity for adaptation to ionizing radiation and desiccation. Positive Darwinian selection is expected to play an important role in this trait, but no data are currently available regarding the role of positive adaptive selection in resistance to ionizing-radiation and tolerance of desiccation. We analyzed the four known genome sequences of IRRB (Deinococcus geothermalis, Deinococcus radiodurans, Kineococcus radiotolerans, and Rubrobacter xylanophilus) to determine the role of positive Darwinian selection in the evolution of resistance to ionizing radiation and tolerance of desiccation.', 'We used the programs MultiParanoid and DnaSP to deduce the sets of orthologs that potentially evolved due to positive Darwinian selection in IRRB. We find that positive selection targets 689 ortholog sets of IRRB. Among these, 58 ortholog sets are absent in ionizing-radiation-sensitive bacteria (IRSB: Escherichia coli and Thermus thermophilus). The most striking finding is that all basal DNA repair genes in IRRB, unlike many of their orthologs in IRSB, are subject to positive selection.",
            "output": [
                "Is basal DNA repair machinery subject to positive selection in ionizing-radiation-resistant bacteria?"
            ]
        },
        {
            "id": "task847-fa7d4e11538b4a85861a01d4d1c9f090",
            "input": "Topical negative pressure (TNP), widely used in wound therapy, is known to stimulate wound edge blood flow, granulation tissue formation, angiogenesis, and revascularization. We have previously shown that application of a TNP of -50 mmHg to the myocardium significantly increases microvascular blood flow in the underlying tissue. We have also shown that a myocardial TNP levels between -75 mmHg and -150 mmHg do not induce microvascular blood flow changes in the underlying myocardium. The present study was designed to elucidate the difference between -25 mmHg and -50 mmHg TNP on microvascular flow in normal and ischemic myocardium.', 'Six pigs underwent median sternotomy. The microvascular blood flow in the myocardium was recorded before and after the application of TNP using laser Doppler flowmetry. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium), and after 20 minutes of LAD occlusion (ischemic myocardium).', 'A TNP of -25 mmHg significantly increased microvascular blood flow in both normal (from 263.3 +/- 62.8 PU before, to 380.0 +/- 80.6 PU after TNP application, * p = 0.03) and ischemic myocardium (from 58.8 +/- 17.7 PU before, to 85.8 +/- 20.9 PU after TNP application, * p = 0.04). A TNP of -50 mmHg also significantly increased microvascular blood flow in both normal (from 174.2 +/- 20.8 PU before, to 240.0 +/- 34.4 PU after TNP application, * p = 0.02) and ischemic myocardium (from 44.5 +/- 14.0 PU before, to 106.2 +/- 26.6 PU after TNP application, ** p = 0.01).",
            "output": [
                "Do a compare between myocardial topical negative pressure levels of -25 mmHg and -50 mmHg in a porcine model?"
            ]
        },
        {
            "id": "task847-720b6d0fcf834991bfac6ff66806b09b",
            "input": "Chronic inflammatory conditions, such as granulomas, are associated with angiogenesis. Mast cells represent the main cell type orchestrating angiogenesis, through the release of their granule content. Therefore, compounds able to modulate mast cell behaviour may be considered as a new pharmacological approach to treat angiogenesis-dependent events. Here, we tested the effect of selective cannabinoid (CB) receptor agonists in a model of angiogenesis-dependent granuloma formation induced by lambda-carrageenin in rats.', 'Granulomas were induced by lambda-carrageenin-soaked sponges implanted subcutaneously on the back of male Wistar rats. After 96 h, implants were removed and granuloma formation was measured (wet weight); angiogenesis was evaluated by histological analysis and by the measurement of haemoglobin content. Mast cells in the granulomas were evaluated histologically and by RT-PCR and immunoblotting analysis for mast cell-derived proteins (rat mast cell protease-5 (rMCP-5) and nerve growth factor). Selective CB1 and CB2 receptor agonists(,) ACEA and JWH-015 (0.001-0.1 mg mL(-1)), were given locally only once, at the time of implantation.', 'The CB1 and CB2 receptor agonists decreased the weight and vascularization of granulomas after 96 h. This treatment also reduced mast cell number and activation in granulomatous tissue. Specifically, these compounds prevented the transcription and expression of rMCP-5, a protein involved in sprouting and advance of new blood vessels.",
            "output": [
                "Do cannabinoids reduce granuloma-associated angiogenesis in rats by controlling transcription and expression of mast cell protease-5?"
            ]
        },
        {
            "id": "task847-bb2a0098e6dd40dfbadcb88b6940ec7b",
            "input": "Smoking parents are the main source of passive smoke exposure in childhood. Only few studies have assessed the effect of maternal or paternal cigarette smoke exposure in childhood on the development and severity of COPD.', 'We recruited n = 251 COPD-patients, n = 113 were clinically stable (no exacerbations for up to 24 years backdated from the day of interview), and - according to their history - n = 138 had more than one exacerbation during this time period. All COPD-patients were interviewed by a physician using a structured questionnaire on main health outcomes, social status, smoking history of their parents and themselves. Furthermore, pulmonary function was measured, and concomitant lung diseases were excluded.', 'Both COPD groups were comparable in age, gender, smoking history at the beginning of the disease, and cigarette pack-years smoked. Patients whose mothers smoked during childhood had poorer lung function values: FEV (1) 45.2 % vs. 54 % (p = 0.037). Non-smoking patients with a history of maternal smoking had a 7-times higher exacerbation rate compared to patients without passive smoke exposure (p = 0.073). Paternal cigarette smoke exposure had no effect.",
            "output": [
                "Does [ Parental smoking and passive smoke exposure in childhood promote the COPD exacerbation rate ]?"
            ]
        },
        {
            "id": "task847-8b41e6000b24408eaddf37997fa3ac72",
            "input": "Before clinical treatment and during transportation, the analgesic therapy offered to patients with painful knee trauma may be quite insufficient. We hypothesize that a femoral nerve blockade for analgesia can be administered in a preclinical setting at the injury site and provides better pain relief than intravenous metamizole, whose analgesic effect is comparable with that of opioids.', 'After an initial clinical investigation, 52 patients were randomized according to computer-generated codes; 26 patients received a femoral nerve blockade and 26 received metamizole. The treatment was started at the injury site and the level of pain on the 100-mm visual analog scale was assessed at the beginning and the end of treatment.', 'Pain and anxiety scores were significantly reduced by half in the femoral nerve blockade group; peripheral vasoconstriction was noted in 26 patients at the injury site and dropped to six at the time of arrival at the hospital. Two of 26 patients in the blockade group did not benefit from the treatment. In the metamizole group, pain and anxiety did not decrease significantly; vasoconstriction persisted in all patients.",
            "output": [
                "Is femoral nerve blockade administered preclinically for pain relief in severe knee trauma more feasible and effective than intravenous metamizole : a randomized controlled trial?"
            ]
        },
        {
            "id": "task847-53b7940b00f84ea1a7fdb060e54d890d",
            "input": "The adaptive immune system seems to play an essential role in the natural course of ovarian cancer. Aim of this study was to establish whether disease-specific survival for patients expressing the tumour antigen p53 is influenced by MHC class I expression or the presence of p53 autoantibodies (p53-Aab).', 'P53 and MHC class I expression were analysed in ovarian cancer tissue of 329 patients by immunohistochemistry using tissue microarrays. For 233 patients, pre-treatment serum samples were available to study the presence of p53 autoantibodies by ELISA. Data were linked to clinicopathological parameters and disease-specific survival.', 'P53 overexpression, MHC class I down-regulation in neoplastic cells and serum p53 autoantibodies were observed in 49.4, 38.9 and 15.9% of patients, respectively. MHC class I down-regulation in p53-overexpressing tumours correlated with a 10-month reduced disease-specific survival in univariate analysis (log-rank 4.10; p=0.043). p53-Aab were strongly correlated with p53 overexpression (p<0.001), but did not influence disease-specific survival.",
            "output": [
                "Is survival of ovarian cancer patients overexpressing the tumour antigen p53 diminished in case of MHC class I down-regulation?"
            ]
        },
        {
            "id": "task847-5a4fd9e988924fe6a93ba299e347b2b9",
            "input": "Conflicting evidence has been reported on the association of prostate-specific antigen velocity (PSAV) with Gleason score in prostate needle biopsy specimens. The Gleason score is an important prognostic indicator for men with prostate cancer, and, in modern practice, it frequently affects treatment decisions. To our knowledge, the relationship between preoperative PSAV and Gleason score in the radical prostatectomy specimen has not been formally demonstrated.', 'A total of 1049 men treated with radical prostatectomy had data on PSAV and Gleason score. Statistical analysis was performed to examine the relationship between the preoperative PSAV and the prostatectomy Gleason score and other adverse tumor features.', 'The median preoperative PSAV was 0.84, 0.97, and 1.39 ng/mL/y in men with a Gleason score of 6, 7, and 8-10, respectively (P = .05). A PSAV greater than 2 ng/mL/y was significantly associated with a prostatectomy Gleason score of 7 or greater on univariate and multivariate analysis. In addition, the preoperative PSAV was significantly lower in men with organ-confined disease (0.82 vs 1.17 ng/mL/y, respectively, P = .002).",
            "output": [
                "Is pSA velocity associated with gleason score in radical prostatectomy specimen : marker for prostate cancer aggressiveness?"
            ]
        },
        {
            "id": "task847-07acba14d6794ea7a86da701c346b9d6",
            "input": "Epidemiologic studies associate environmental tobacco smoke (ETS) exposure with childhood asthma.', 'To investigate whether specific pathophysiological alterations that contribute to asthma development in human beings can be induced in infant monkeys after perinatal ETS exposure.', 'Rhesus macaque fetuses/infants were exposed to ETS at 1 mg/m(3) of total suspended particulate matter from 50 days gestational age to 2.5 months postnatal age. Inflammatory and neural responses to ETS exposure were measured in the infant monkeys.', 'Perinatal ETS exposure could induce systemic and local responses, which include significant elevation of plasma levels of C5a and brain-derived neurotrophic factor, as well as significant increases in pulmonary expression of proinflammatory cytokine TNF-alpha and T(H)2 cytokine IL-5, chemokine monocyte chemoattractant protein 1, and the density of substance P-positive nerves along the bronchial epithelium. Perinatal ETS exposure also significantly increased the numbers of mast cells, eosinophils, monocytes, and lymphocytes in the lungs of infant monkeys. In addition, ex vivo measurements showed significantly increased levels of IL-4 and brain-derived neurotrophic factor in the culture supernatant of PBMCs. Interestingly, as an important component of cigarette smoke, LPS was detected in the plasma of infant monkeys subjected to perinatal exposure to ETS. In contrast, an inhibitory effect of perinatal ETS exposure was also observed, which is associated with decreased phagocytic activity of alveolar macrophages and a significantly decreased level of nerve growth factor in the bronchoalveolar lavage fluid.",
            "output": [
                "Does perinatal environmental tobacco smoke exposure alter the immune response and airway innervation in infant primates?"
            ]
        },
        {
            "id": "task847-01802db270c54e61adf23bc7c948dc18",
            "input": "Domestication of chicken is believed to have occurred in Southeast Asia, especially in Indus valley. However, non-inclusion of Indian red jungle fowl (RJF), Gallus gallus murghi in previous studies has left a big gap in understanding the relationship of this major group of birds. In the present study, we addressed this issue by analyzing 76 Indian birds that included 56 G. g. murghi (RJF), 16 G. g. domesticus (domestic chicken) and 4 G. sonneratii (Grey JF) using both microsatellite markers and mitochondrial D-loop sequences. We also compared the D-loop sequences of Indian birds with those of 779 birds obtained from GenBank.', \"Microsatellite marker analyses of Indian birds indicated an average FST of 0.126 within G. g. murghi, and 0.154 within G. g. domesticus while it was more than 0.2 between the two groups. The microsatellite-based phylogenetic trees showed a clear separation of G. g. domesticus from G. g. murghi, and G. sonneratii. Mitochondrial DNA based mismatch distribution analyses showed a lower Harpending's raggedness index in both G. g. murghi (0.001515) and in Indian G. g. domesticus (0.0149) birds indicating population expansion. When meta analysis of global populations of 855 birds was carried out using median joining haplotype network, 43 Indian birds of G. g. domesticus (19 haplotypes) were distributed throughout the network sharing haplotypes with the RJFs of different origins.",
            "output": [
                "Does genetic evidence from Indian red jungle fowl corroborate multiple domestication of modern day chicken?"
            ]
        },
        {
            "id": "task847-575871bcfc0744c597b5202078ebc363",
            "input": "Estrogen-progestogen oral contraceptive (OC) use is associated with abnormal lipid metabolism, impaired glucose tolerance and high prevalence of vascular complications. OC use has been shown to alter the requirements for folic acid. Therefore, the aim of the present study was to clarify the influence of dietary folic acid on OC-induced impaired glucose tolerance and abnormal plasma lipid profile in female Sprague-Dawley rats. Vehicle-treated and OC-treated rats were fed for 6 weeks with a control diet (750mug folic acid/kg diet) while OC-treated folic acid deficient (FD) rats were fed for 6 weeks with a folic acid-deficient diet (250mug folic acid/kg diet). OC receiving rats were treated with a combination of OC steroids (ethinyl estradiol and norgestrel) by oral gavage. OC treatment resulted in rats receiving folic acid deficient diet in impaired glucose tolerance, decreased high-density lipoprotein (HDL)-cholesterol and increased low-density lipoprotein (LDL)-cholesterol when compared with control rats. However, OC treatment did not result in impaired glucose tolerance or disturbed plasma lipid profile in rats receiving the same folic acid level as the controls. OC treatment led to significant decreases in plasma levels of 17beta-estradiol and testosterone in both groups. OC administration in rats with folic acid deficient diet significantly lower HDL-cholesterol and higher LDL-cholesterol levels while plasma levels of 17beta-estradiol and testosterone were similar in both OC-treated groups.",
            "output": [
                "Does low dietary folate impair glucose tolerance and plasma lipid profile in oral contraceptive-treated rats?"
            ]
        },
        {
            "id": "task847-63e2851a6def4782adc0c65423815c22",
            "input": "The transient receptor potential vanilloid-4 (TRPV4) is an osmosensitive channel that responds to mechanical stimulation. We hypothesized that TRPV4 could be important in visceral nociception and in the development of hypersensitivity.', 'TRPV4 expression was investigated by immunohistochemistry and reverse transcription-polymerase chain reaction. Calcium signaling and patch-clamp studies were performed in dorsal root ganglia (DRG) neurons validating the use of 4alphaPDD as a selective TRPV4 agonist. The effects of TRPV4 activation on visceral nociception were evaluated in mice that received intracolonically TRPV4 agonist (4 alpha-phorbol 12,13-didecanoate [4alphaPDD]) and in TRPV4-deficient mice in which abdominal muscle contractions in response to colorectal distention (CRD) were recorded. Intervertebral injections of TRPV4 or mismatch small interfering RNA (siRNA) were used to specifically down-regulate TRPV4 expression in sensory neurons and to investigate the role of TRPV4 in basal visceral nociception or in protease-activated receptor 2 (PAR(2)) activation-induced visceral hypersensitivity.', 'TRPV4 agonist 4alphaPDD specifically activated a cationic current and calcium influx in colonic projections of DRG neurons and caused dose-dependent visceral hypersensitivity. TRPV4-targeted but not mismatched siRNA intervertebral treatments were effective at reducing basal visceral nociception, as well as 4alphaPDD or PAR(2) agonist-induced hypersensitivity. Effects of the TRPV4 ligand were lost in TRPV4-deficient mice.",
            "output": [
                "Does transient receptor potential vanilloid-4 have a major role in visceral hypersensitivity symptoms?"
            ]
        },
        {
            "id": "task847-dbe5abf9590144319c260de5f80dd737",
            "input": "Several experimental studies have observed better outcomes after glycine treatment in patients with endotoxin-induced liver injuries, but its molecular mechanism is not yet fully understood. The purpose of this study was to evaluate the hypothesis that glycine attenuates endotoxin-induced liver injury by affecting endotoxin signal transduction in liver macrophages.', 'An animal model of endotoxin-induced liver injury was established by intraperitoneally injecting mice with 10 mg/kg body weight endotoxin fed a pretreatment diet with or without 5% (w/w) glycine. Blood and liver samples were obtained for analysis of liver morphology and to determine concentrations of alanine aminotransferase, endotoxin receptor Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-10 at various time points after injection. To investigate the effect of glycine on liver macrophages, Kupffer cells (KCs) were isolated and challenged by LPS (100 ng/mL), with or without glycine (4 mmol/l) pretreatment, and the expressions of TLR4, IL-10, and TNF-alpha were assayed at mRNA and protein levels. DNA-binding activity of nuclear factor-kappa B (NF-kappaB) was also analyzed using enzyme-linked immunosorbent assay.', 'Dietary glycine significantly improved the survival rate of endotoxemic mice (P < .05), whereas serum alanine aminotransferase and TNF-alpha levels were significantly decreased at different time points (P < .05); IL-10 levels were increased (P < .05). Concurrently, LPS-induced hepatic tissue injury was attenuated as indicated by morphologic analysis; secretion of IL-10 in liver tissue (P < .05) was enhanced; and expression of TLR4 and TNF-alpha in liver tissue was downregulated (P < .05). Consistent with these in vivo experiments, enhanced secretion of IL-10 and inhibited expression of TLR4 and TNF-alpha caused by glycine pretreatment were also observed in LPS-stimulated KCs. NF-kappaB DNA-binding activity was also significantly inhibited by glycine (P < .05, respectively).",
            "output": [
                "Does glycine attenuate endotoxin-induced liver injury by downregulating TLR4 signaling in Kupffer cells?"
            ]
        },
        {
            "id": "task847-1af234b7063c4b129640fe8a28222797",
            "input": "The majority of studies assessing executive function in attention deficit disorder (ADD) have shown deficits in attentional set shifting using either the Wisconsin card sorting task or the intra-dimensional/extra-dimensional set-shifting task (ID/ED). Damage to the prefrontal cortex in humans, primates, and rodents impairs extra-dimensional (ED) shifts. Noradrenergic depletion of the medial prefrontal cortex in rats is sufficient to impair attentional set shifting. Atomoxetine, a selective norepinephrine (NE) re-uptake inhibitor, is hypothesized to produce beneficial effects in patient with ADD by augmenting NE release in prefrontal cortex.', 'We assessed the effects of systemic administration of atomoxetine (0.0, 0.1, 0.3, and 0.9 mg/kg/ml) in normal and noradrenergically lesioned (NE-LX) rats on attentional-set shifts. We replicated findings showing NE-LX rats are selectively impaired on the ED shifts but not reversals or other discriminations.', 'Atomoxetine remediated the attentional set-shifting impairments in NE-LX rats but impaired ED performance of non-lesioned rats.",
            "output": [
                "Does atomoxetine reverse attentional deficits produced by noradrenergic deafferentation of medial prefrontal cortex?"
            ]
        },
        {
            "id": "task847-37dc7d1a85f14ddcacd4d1abdac2bbdd",
            "input": "To simultaneously study the effect of a selective cyclooxygenase-2 (COX-2) inhibitor and that of a classic non-steroidal anti-inflammatory drug (NSAID) on the expression of pro-inflammatory genes in the cartilage of patients with severe knee osteoarthritis (OA) and in cultured human OA chondrocytes.', 'A 3-month clinical trial was carried out on 30 patients with severe knee OA scheduled for knee replacement surgery. Patients were randomized into two groups: patients treated with celecoxib (CBX) and patients treated with aceclofenac (ACF). OA patients who did not want to be treated served as the control group. After surgery, cartilage was processed for molecular biology studies. We also employed cultured chondrocytes from different OA patients to examine NSAID effects on pro-inflammatory gene expression in cells stimulated with interleukin (IL)-1beta.', 'Both CBX and ACF inhibited COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and inducible nitric oxide synthase (iNOS) synthesis in the articular cartilage of OA patients. In cultured chondrocytes, both NSAID decreased COX-2 and mPGES-1 synthesis and prostaglandin E2 (PGE2) release induced by IL-1beta, while no effect was observed on nitric oxide or iNOS synthesis. In OA patients, only CBX decreased tumor necrosis factor alpha and IL-1beta expression in the cartilage, while both NSAID diminished IL-1beta induced cytokine synthesis in cultured OA chondrocytes.",
            "output": [
                "Does long-term NSAID treatment directly decrease COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis?"
            ]
        },
        {
            "id": "task847-1f672e5fd8a046ad9a69eb0f2a7b9bd2",
            "input": "An anti-angiogenic state has been described in patients with preeclampsia, small-for-gestational age (SGA) fetuses and fetal death, and changes in the concentration of circulating angiogenic and anti-angiogenic factors can precede the clinical recognition of preeclampsia and SGA by several weeks. Gene deletion studies demonstrate that a selective group of endothelial growth factors are required for vascular development, including members of the vascular endothelial growth factor (VEGF) family, as well as angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), both ligands for the tyrosine kinase endothelial cell receptor Tie-2. These angiogenic factors have been proposed to promote angiogenesis in a coordinated and complementary fashion. Soluble Tie-2 (sTie-2) is the soluble form of the Tie-2 receptor, which is detectable in biological fluids. The purpose of this study was to determine whether patients with preeclampsia and mothers who deliver a SGA neonate have changes in the plasma concentrations of sTie-2.', 'This cross-sectional study included patients in the following groups: (1) non-pregnant women (n = 40), (2) women with normal pregnancies (n = 135), (3) patients with preeclampsia (n = 112), and (4) patients who delivered an SGA neonate (n = 53). Maternal plasma concentrations of sTie-2 were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis.', '(1) The median maternal plasma concentration of sTie-2 was lower in normal pregnant women than in non-pregnant women [median 16.0 ng/mL (range 5.0-71.6) vs. median 20.7 ng/mL (range 10.8-52.4), respectively; p = 0.01)). (2) Plasma sTie-2 concentrations in normal pregnancy changed significantly as a function of gestational age. (3) Patients with preeclampsia and those who delivered SGA neonates had a lower median maternal plasma concentration of sTie-2 than those with a normal pregnancy [preeclampsia: median 14.9 ng/mL (range 4.9-67.3); SGA: median 10.9 ng/mL (range 5.1-29.1); normal pregnancy: median 16.0 ng/mL (range 5.0-71.6); p = 0.048 and p < 0.001, respectively]. (4) Patients with SGA neonates had a lower median plasma concentration of sTie-2 than that of those with preeclampsia [median 10.9 ng/mL (range 5.1-29.1) vs. median 14.9 ng/mL (range 4.9-67.3), respectively; p < 0.001]. (5) Patients with early-onset preeclampsia (<or=34 weeks) had lower concentrations of sTie-2 than women with late-onset preeclampsia (>34 weeks) median of delta values: -0.13 ng/mL (range -0.47-0.58) vs. median of delta values: -0.09 ng/mL (range: -0.60-0.58), respectively; p = 0.043]. In contrast, there were no significant differences in the maternal plasma sTie-2 concentration between women with severe and mild preeclampsia (p = 0.6).",
            "output": [
                "Are preeclampsia and small-for-gestational age associated with decreased concentrations of a factor involved in angiogenesis : soluble Tie-2?"
            ]
        },
        {
            "id": "task847-638894fc939d47bcaad2763d1ccc1400",
            "input": "The Los Angeles Motor Scale (LAMS) is a brief 3-item stroke severity assessment measure designed for prehospital and Emergency Department use.', 'The LAMS and NIHSS were scored in under-12-hour acute anterior circulation ischemic stroke patients. Stroke severity ratings were correlated with cervicocerebral vascular occlusion on CTA, MRA, and catheter angiography. Receiver operating curves, c statistics, and likelihood ratios were used to evaluate the predictive value for vascular occlusion of stroke severity ratings.', 'Among 119 patients, mean age was 67 (+/-18), 45% were male. Time from onset to ED arrival was mean 190 minutes (range 10 to 660). Persisting large vessel occlusions (PLVOs) were present in 62% of patients. LAMS stroke severity scores were higher in patients harboring a vascular occlusion, median 5 (IQR 4 to 5) versus 2 (IQR 1 to 3). Similarly, NIHSS stroke severity scores were higher in PLVO patients, 19 (14 to 24) versus 5 (3 to 7). ROC curves demonstrated that the LAMS was highly effective in identifying patients with PLVOs, c statistic 0.854. At the optimal threshold of 4 or higher, LAMS scores showed sensitivity 0.81, specificity 0.89, and overall accuracy 0.85. LAMS performance was comparable to NIHSS performance (c statistic 0.933). The positive likelihood ratio associated with a LAMS score > or = 4 was 7.36 and the negative likelihood ratio 0.21.",
            "output": [
                "Does a brief prehospital stroke severity scale identify ischemic stroke patients harboring persisting large arterial occlusions?"
            ]
        },
        {
            "id": "task847-b786cbc6658e4591915d7de9f6d21dda",
            "input": "That certain vessels might be at so-called geometric risk of atherosclerosis rests on assumptions of wide interindividual variations in disturbed flow and of a direct relationship between disturbed flow and lumen geometry. In testing these often-implicit assumptions, the present study aimed to determine whether investigations of local risk factors in atherosclerosis can indeed rely on surrogate geometric markers of disturbed flow.', 'Computational fluid dynamics simulations were performed on carotid bifurcation geometries derived from MRI of 25 young adults. Disturbed flow was quantified as the surface area exposed to low and oscillatory shear beyond objectively-defined thresholds. Interindividual variations in disturbed flow were contextualized with respect to effects of uncertainties in imaging and geometric reconstruction. Relationships between disturbed flow and various geometric factors were tested via multiple regression.', 'Relatively wide variations in disturbed flow were observed among the 50 vessels. Multiple regression revealed a significant (P<0.002) relationship between disturbed flow and both proximal area ratio (beta approximately 0.5) and bifurcation tortuosity (beta approximately -0.4), but not bifurcation angle, planarity, or distal area ratio. These findings were shown to be insensitive to assumptions about the flow conditions and to the choice of disturbed flow indicator and threshold.",
            "output": [
                "Does geometry of the carotid bifurcation predict its exposure to disturbed flow?"
            ]
        },
        {
            "id": "task847-9bed9061fa3e4026a8fe97080c21cdb7",
            "input": "Leaks of the blood-brain barrier can be detected on postcontrast-enhanced T1-weighted MRIs. Although early disruptions of the blood-brain barrier appear to be an important risk factor for tissue plasminogen activator-related hemorrhages in rodents, little is known about their incidence and consequences in human stroke.', \"This is a retrospective analysis of a prospectively collected stroke database over the past 6 years. In 52 patients, multimodal MRI (including diffusion-weighted, perfusion-weighted, and postcontrast-enhanced T1-weighted MRI to detect blood-brain barrier changes) had been performed immediately before systemic thrombolysis and in 48 patients within a median of 30 minutes (interquartile range: 30 to 60 minutes) after recombinant tissue plasminogen activator treatment. The incidence of symptomatic hemorrhage (SICH), defined as any parenchymal hemorrhage leading to deterioration in the patient's clinical condition, was related to several clinical and imaging variables, including early blood-brain barrier changes.\", 'Overall, SICH was detected in 9 (9%) patients and among these, 2 died. Although no blood-brain barrier changes were detectable before thrombolysis, 3 of 48 patients (6.25%) had a parenchymal gadolinium enhancement in the areas of initial infarction after tissue plasminogen activator treatment. All 3 patients developed SICHs at sites corresponding to the areas of enhancement. The presence of a parenchymal enhancement was significantly associated with SICH (P<0.01), whereas other clinical and imaging variables did not predict SICH in this series.",
            "output": [
                "Does early disruption of the blood-brain barrier after thrombolytic therapy predict hemorrhage in patients with acute stroke?"
            ]
        },
        {
            "id": "task847-1cdaa86e6471490ba259ca994dc59b88",
            "input": "The proportion of dendritic cell subpopulations in the skin is important for the severity of atopic dermatitis because topical treatment with tacrolimus leads to rapid depletion of inflammatory dendritic epidermal cells, whereas Langerhans cells (LCs) predominate in cured sites.', 'The effects of tacrolimus and TGF-beta1 on LC differentiation and the idea of tacrolimus skewing the differentiation of epidermal precursors to LCs were evaluated.', 'The presence of LC markers, MHC, and costimulatory molecules and stimulatory capacity toward T cells of monocyte-derived LCs were analyzed. Skin samples of patients with atopic dermatitis were assessed by means of immunofluorescence microscopy before and after tacrolimus treatment. TGF-beta production of skin cells was analyzed.', 'Tacrolimus and TGF-beta1 act synergistically on the generation of LCs and the expression of CD40, CD80, CD86, CD83, and MHC II; stabilize TGF-beta receptor II expression; and decrease the stimulatory capacity of LCs toward T cells. In vivo the number of epidermal LCs in tacrolimus-treated skin increased.",
            "output": [
                "Do tacrolimus and TGF-beta act synergistically on the generation of Langerhans cells?"
            ]
        },
        {
            "id": "task847-32ec102daea94a718aaa9388e1f07bb9",
            "input": "Virus-induced wheezing episodes in infancy often precede the development of asthma. Whether infections with specific viral pathogens confer differential future asthma risk is incompletely understood.', 'To define the relationship between specific viral illnesses and early childhood asthma development.', 'A total of 259 children were followed prospectively from birth to 6 years of age. The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using nasal lavage, culture, and multiplex reverse transcriptase-polymerase chain reaction. The relationships of these virus-specific wheezing illnesses and other risk factors to the development of asthma were analyzed.', 'Viral etiologies were identified in 90% of wheezing illnesses. From birth to age 3 years, wheezing with respiratory syncytial virus (RSV) (odds ratio [OR], 2.6), rhinovirus (RV) (OR, 9.8), or both RV and RSV (OR , 10) was associated with increased asthma risk at age 6 years. In Year 1, both RV wheezing (OR, 2.8) and aeroallergen sensitization (OR, 3.6) independently increased asthma risk at age 6 years. By age 3 years, wheezing with RV (OR, 25.6) was more strongly associated with asthma at age 6 years than aeroallergen sensitization (OR, 3.4). Nearly 90% (26 of 30) of children who wheezed with RV in Year 3 had asthma at 6 years of age.",
            "output": [
                "Do wheezing rhinovirus illnesses in early life predict asthma development in high-risk children?"
            ]
        },
        {
            "id": "task847-c5111642c7534215976801c514d069ae",
            "input": "Gene therapy is a new method used to induce cancer cell differentiation. Our group previously showed that transfection of the gef gene from Escherichia coli, related to cell-killing functions, may be a novel candidate for cancer gene therapy. Its expression leads to cell cycle arrest unrelated to the triggering of apoptosis in MS-36 melanoma cells.', 'To determine the basis of the antiproliferative effect of the gef gene in this cell line.', 'Transmission electron microscopy, apoptosis analysis by confocal microscopy, flow cytometry and immunocytochemical analysis were used.', 'Ultrastructural analysis showed a strikingly different morphology after treatment with dexamethasone and expression of the gef gene, with large accumulations of pigment throughout the cell cytoplasm and presence of melanosomes in different stages of development. High mitochondrial turnover and myeloid bodies, characteristics of neurone cells, were also observed. In addition, both immunocytochemical and indirect immunofluorescence analysis demonstrated a significant decrease in HMB-45, Ki-67 and CD44 antigen expression and an increase in S100 and p53 expression in gef gene-transfected MS-36 melanoma cells that were correlated with the duration of dexamethasone treatment. In the present work, we report that gef gene not only reduces cell proliferation in transfected melanoma MS-36TG cell line but also induces morphological changes clearly indicative of melanoma cell differentiation and a reduction in tumour malignancy.",
            "output": [
                "Are tumour malignancy loss and cell differentiation associated with induction of gef gene in human melanoma cells?"
            ]
        },
        {
            "id": "task847-5896b5431a6243868efba3fbd022de37",
            "input": "Extended-release niacin effectively lowers plasma TG levels and raises plasma high-density lipoprotein (HDL) cholesterol levels, but the mechanisms responsible for these effects are unclear.', 'We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to placebo, on the kinetics of apolipoprotein (apo) A-I and apoA-II in HDL, apoB-100 in TG-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), and apoB-48 in TRL in 5 men with combined hyperlipidemia. Niacin significantly increased HDL cholesterol and apoA-I concentrations, associated with a significant increase in apoA-I production rate (PR) and no change in fractional catabolic rate (FCR). Plasma TRL apoB-100 levels were significantly lowered by niacin, accompanied by a trend toward an increase in FCR and no change in PR. Niacin treatment significantly increased TRL apoB-48 FCR but had no effect on apoB-48 PR. No effects of niacin on concentrations or kinetic parameters of IDL and LDL apoB-100 and HDL apoA-II were noted. The addition of lovastatin to niacin promoted a lowering in LDL apoB-100 attributable to increased LDL apoB-100 FCR.",
            "output": [
                "Does extended-release niacin alter the metabolism of plasma apolipoprotein ( Apo ) A-I and ApoB-containing lipoproteins?"
            ]
        },
        {
            "id": "task847-670bdeb96f384e4b99dd4b61ec615369",
            "input": "The metabolic syndrome (MetS) is characterized by insulin resistance and dyslipidemia that may accelerate atherosclerosis. Disturbed apolipoprotein (apo) C-III metabolism may account for dyslipidemia in these subjects. Atorvastatin and fenofibrate decrease plasma apoC-III, but the underlying mechanisms are not fully understood.', 'The effects of atorvastatin (40 mg/d) and fenofibrate (200 mg/d) on the kinetics of very-low density lipoprotein (VLDL)-apoC-III were investigated in a crossover trial of 11 MetS men. VLDL-apoC-III kinetics were studied, after intravenous d(3)-leucine administration using gas chromatography-mass spectrometry and compartmental modeling. Compared with placebo, both atorvastatin and fenofibrate significantly decreased (P<0.001) plasma concentrations of triglyceride, apoB, apoB-48, and total apoC-III. Atorvastatin, not fenofibrate, significantly decreased plasma apoA-V concentrations (P<0.05). Both agents significantly increased the fractional catabolic rate (+32% and +30%, respectively) and reduced the production rate of VLDL-apoC-III (-20% and -24%, respectively), accounting for a significant reduction in VLDL-apoC-III concentrations (-41% and -39%, respectively). Total plasma apoC-III production rates were not significantly altered by the 2 agents. Neither treatment altered insulin resistance and body weight.",
            "output": [
                "Do atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome?"
            ]
        },
        {
            "id": "task847-3d9e747511b34e83b105455f68567977",
            "input": "Experimental studies suggest that adipose inflammation is etiologically linked to obesity-induced systemic disease. Our goal was to characterize the state of inflammation in human fat in relation to vascular function and metabolic parameters in obese individuals.', 'We collected subcutaneous abdominal fat in 77 obese subjects (BMI >or=30 kg/m(2)) and quantified adipose macrophage population using targeted immunohistochemistry. Brachial artery vasodilator function was examined using high-resolution vascular ultrasound. In 50 subjects, an inflamed adipose phenotype characterized by tissue macrophage accumulation in crown-like structures was associated with systemic hyperinsulinemia and insulin resistance (HOMA-IR 5.5+/-4.5 versus 2.6+/-1.9, P=0.002) and impaired endothelium-dependent flow-mediated vasodilation (8.5+/-4.4% versus 10.8+/-3.8%, P<0.05), as compared to subjects with quiescent noninflamed adipose architecture (n=27). Macrophage retention in fat was linked to upregulated tissue CD68 and tumor necrosis factor (TNF)-alpha mRNA expression in addition to increased plasma hs-CRP.",
            "output": [
                "Is adipose macrophage infiltration associated with insulin resistance and vascular endothelial dysfunction in obese subjects?"
            ]
        },
        {
            "id": "task847-b26774083fdc4907b7ba3a6295b762c3",
            "input": "Tibia fracture in rats evokes chronic hindpaw warmth, edema, allodynia, and regional osteopenia, a syndrome resembling complex regional pain syndrome (CRPS). Previous studies suggest that the pathogenesis of some of these changes involves an exaggerated regional inflammatory response to injury and we postulated that inflammatory cytokines contribute to the development of CRPS-like changes after fracture.', 'The distal tibia was fractured and the hindlimb casted for 4 weeks. The rats were given drinking water with or without the cytokine inhibitor pentoxifylline (PTX) starting the day before fracture and continuing for 4 weeks, after which time the cast was removed and multiple assays were performed in the hindpaw. PCR and immunoassays were used to evaluate changes in cytokine expression. Bilateral hindpaw thickness, temperature, and nociceptive thresholds were determined, and bone microarchitecture was measured by microcomputed tomography (microCT).', 'Tibia fracture chronically up-regulated TNFalpha, IL-1beta and IL-6 mRNA and protein levels in hindpaw skin and PTX treatment significantly reduced the mRNA expression and cytokine protein levels for all these cytokines. PTX inhibited the nociceptive sensitization and some vascular changes, but had insignificant effects on most of the bone-related parameters measured in these studies. Immunostaining of hindpaw skin was negative for immunocyte infiltration at 4 weeks post-fracture.",
            "output": [
                "Does pentoxifylline attenuate nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome?"
            ]
        },
        {
            "id": "task847-73956b506b844678b3b3e7cd4a2d490e",
            "input": "Fatty liver is the hepatic manifestation of obesity, but community-based assessment of fatty liver among unselected patients is limited. We sought to determine the feasibility of and optimal protocol for quantifying fat content in the liver in the Framingham Heart Study using multidetector computed tomography (MDCT) scanning.', 'Participants (n = 100, 49% women, mean age 59.4 years, mean body mass index 27.8 kg/m(2)) were drawn from the Framingham Heart Study cohort. Two readers measured the attenuation of the liver, spleen, paraspinal muscles, and an external standard from MDCT scans using multiple slices in chest and abdominal scans.', 'The mean measurement variation was larger within a single axial computed tomography (CT) slice than between multiple axial CT slices for the liver and spleen, whereas it was similar for the paraspinal muscles. Measurement variation in the liver, spleen, and paraspinal muscles was smaller in the abdomen than in the chest. Three versus six measures of attenuation in the liver and two versus three measures in the spleen gave reproducible measurements of tissue attenuation (intraclass correlation coefficient [ICCC] of 1 in the abdomen). Intra reader and interreader reproducibility (ICCC) of the liver-to-spleen ratio was 0.98 and 0.99, the liver-to-phantom ratio was 0.99 and 0.99, and the liver-to-muscle ratio was 0.93 and 0.86, respectively.",
            "output": [
                "Is liver fat reproducibly measured using computed tomography in the Framingham Heart Study?"
            ]
        },
        {
            "id": "task847-a3c7ce43849c4ffc905b66d08ad17d8f",
            "input": "We aimed to investigate structural abnormalities in first-episode remitted geriatric depression (RGD) with optimized voxel-based morphometry (VBM) in closely matched patients and healthy control subjects and examine the relationship of performances on neuropsychological tests with regional gray matter volumes.', 'Nineteen subjects with first-episode RGD and 16 well-matched healthy control subjects were recruited for this study, and neuropsychological tests and magnetic resonance imaging were conducted on the subjects. The differences in regional gray matter volume were determined between these two groups by optimized VBM.', 'The volumes of right superior frontal cortex, left postcentral cortex, and right middle temporal gyrus were significantly smaller in patients with RGD relative to healthy control subjects. However, patients with RGD had larger left cingulate gyrus volume compared with healthy control subjects. There was a significant negative correlation between left cingulate gyrus volume and Rey Auditory Verbal Learning Test delayed recall raw score in patients with RGD.",
            "output": [
                "Are regional gray matter changes associated with cognitive deficits in remitted geriatric depression : an optimized voxel-based morphometry study?"
            ]
        },
        {
            "id": "task847-8af7b8432cc84681979f4b6c1a90892b",
            "input": "The assessment of body posture control can be time consuming and cumbersome due to the complexity and the multimodal influence of a multiply influenced system. Various types of equine paces, such as stepping, trotting or galloping, result in acceleration and deceleration forces of different magnitude. These forces induce, in the horseman, reflexes that mediate motor activity to sustain posture balance and counterbalance the gravitational pull. However, there is a paucity of real life data regarding the extent of the various postural subsystems that are recruited to control postural balance in specific equine disciplines, such as classical dressage, show jumping, or vaulting. This study was conducted to bridge that gap.', 'The aim of this explorative study was to identify the types of the postural subsystems involved in balance control and assess the magnitude of their activities during classical dressage, show jumping, vaulting, and versatility riding.', '144 horseback riders (8.1 % males) aged 17.3 +/- 2.9 years and 38 age matched controls (non riders) were investigated. The riders studied were competing in dressage, show jumping, vaulting, and versatility. In each individual, postural control was investigated by means of the \"interactive balance system (IBS)\" that enabled us to determine the spectral power in the following four standard frequency bands: F 1 (0.03 - 0.1 Hz), F 2 - 4 (0.1 - 0.5 Hz), F 5 - 6 (0.5 - 1.0 Hz), and F 7 - 8 (1.0 - 3.0 Hz). In addition, three motorical output indices were calculated: heel-to-toe-ratio (HTR), synchronization of feet (SYNC), and the global stability index of postural balance (STAB). Furthermore, each individual was interviewed regarding riding time, frequency and discipline and also about other sports activities and disorders of health.', 'The mean training period of the horseback riders was 122 +/- 45.8 months, and mean weekly frequency of training was 5.5 +/- 1.8 days per week. Balance control was most effective in dressage and vaulting riders and least effective in show jumping competitors: HTR was 51 +/- 8 % (dressage), 48 +/- 8 % (show jumping), 47 +/- 8 % (versatility), 51 +/- 7 % (vaulting); SYNC was 523 +/- 124a. i. (dressage), 497 +/- 156a. i. (show jumping), 468 +/- 155a. i. (versatility), 589 +/- 126a. i. (vaulting). Spectral analysis revealed significantly higher power in F 1, F 2 - 4, and F 7 - 8 in dressage competition than in the other equestrian disciplines but not compared with the controls. Significantly differences between riders versus non riders were only found in HTR (p = 0.045) und SYNC (p = 0.009).",
            "output": [
                "Are [ Specific riding styles associated with specific effects on bodily posture control ]?"
            ]
        },
        {
            "id": "task847-3035098792564e4b9901441b92a8e28d",
            "input": "Antioxidant therapy has shown some promise in critical care medicine in which glutathione depletion and heart failure are often seen in critically ill patients. This study was designed to examine the impact of glutathione depletion and the free radical scavenger, metallothionein (MT), on cardiac function.', 'Friend virus B and MT transgenic mice were given the glutathione synthase inhibitor buthionine sulfoximine (buthionine sulfoximine [BSO], 30 mmol/L) in drinking water for 2 wks.', 'Echocardiographic and cardiomyocyte functions were evaluated, including myocardial geometry, fraction shortening, peak shortening, time-to-90% relengthening (TR90), maximal velocity of shortening/relengthening (+/-dL/dt), intracellular Ca2+ rise, sarcoplasmic reticulum Ca2+ release, and intracellular Ca2+ decay rate. Sacro (endo)plasmic reticulum Ca2+-ATPase function was evaluated by 45Ca uptake. Highly reactive oxygen species, caspase-3, and aconitase activity were detected by fluorescent probe and colorimetric assays.', 'BSO elicited lipid peroxidation, protein carbonyl formation, mitochondrial damage, and apoptosis. BSO also reduced wall thickness, enhanced end systolic diameter, depressed fraction shortening, peak shortening, +/-dL/dt, sarcoplasmic reticulum Ca2+ release, 45Ca uptake, and intracellular Ca2+ decay, leading to prolonged TR90. BSO-induced mitochondrial loss and myofilament aberration. MT transgene itself had little effect on myocardial mechanics and ultrastructure. However, it alleviated BSO-induced myocardial functional, morphologic, and carbonyl changes. Western blot analysis showed reduced expression of sacro (endo)plasmic reticulum Ca2+-ATPase2a, Bcl-2 and phosphorylated GSK-3beta, enhanced calreticulin, Bax, p53, myosin heavy chain-beta isozyme switch, and IkappaB phosphorylation in FVB-BSO mice, all of which with the exception of p53 were nullified by MT.",
            "output": [
                "Does metallothionein alleviate glutathione depletion-induced oxidative cardiomyopathy in murine hearts?"
            ]
        },
        {
            "id": "task847-674b6340c78b47848e5efe98a9fa7486",
            "input": "Accurate dosimetry was shown to be critical to achieve effective photodynamic therapy (PDT). This study aimed to assess the reliability of in vivo protoporphyrin IX (PpIX) fluorescence photobleaching as a predictive tool of the hexaminolevulinate PDT (HAL-PDT) response in a rat model of advanced ovarian cancer.', 'Intraperitoneal 10(6) NuTu 19 cells were injected in 26 female rats Fisher 344. Peritoneal carcinomatosis was obtained 26 days post-tumor induction. Four hours post-intraperitoneal HAL (Photocure ASA, Oslo, Norway) injection, a laparoscopic procedure (D-light AutoFluorescence system, Karl Storz endoscope, Tuttlingen, Germany) and a fluorescence examination were made for 22 rats. The first group (LASER group, n=26) was illuminated with laser light using a 532 nm KTP laser (Laser Quantum, Stockport, UK) on 1 cm(2) surface at 45 J/cm(2). The second group (NO LASER group, n=26) served as controls. Biopsies were taken 24 hours after PDT. Semi-quantitative histology was performed and necrosis value was determined: 0--no necrosis to 4--full necrosis. Fluorescence was monitored before and after illumination on complete responders (NV=3-4; n=20) and non-responders (NV=0-2; n=6).', 'High PpIX photobleaching corresponded with complete responders whereas low photobleaching corresponded with non-responders (P<0.05). A direct linear correlation was shown between photobleaching and necrosis (R(2)=0.89).",
            "output": [
                "Is protoporphyrin IX fluorescence photobleaching a useful tool to predict the response of rat ovarian cancer following hexaminolevulinate photodynamic therapy?"
            ]
        },
        {
            "id": "task847-89e8a80eec254c958a3825c7bac354a1",
            "input": "A common variant of the IGF-I gene has been shown to be associated with cardiovascular disease in adulthood. The objective of this study was to examine whether this variant of the IGF-I gene is associated with blood pressure and left heart dimensions in early childhood.', 'This study was embedded in the Generation R Study, a population-based prospective cohort study from foetal life onwards. IGF-I promoter region was genotyped in DNA obtained from cord blood. Blood pressure (systolic and diastolic) and echocardiography (left ventricular mass, left atrial diameter and aortic root diameter) measurements were performed at the age of 2 years. Analyses were performed in 538 subjects.', 'Eight alleles of the IGF-I promoter region were identified. In total, 43% of the subjects were homozygous for the 192 bp allele (wild type), 46% were heterozygous and 11% were non-carriers. Significantly lower systolic and diastolic blood pressures were found in non-carrier subjects (difference compared with homozygous subjects: -4.4 (95% confidence interval (CI) -7.8 to -1.1) mmHg and -3.5 (95% CI: -6.9 to -0.1) mm respectively). No significant differences were found for left heart dimensions at the age of 2 years. No association was found when we used a previously proposed alternative classification of the IGF-I gene.",
            "output": [
                "Is a variant of the IGF-I gene associated with blood pressure but not with left heart dimensions at the age of 2 years : the Generation R Study?"
            ]
        },
        {
            "id": "task847-01c97d247f3441ff895cea2bb668d227",
            "input": "Heterogeneous ribonucleoprotein K (hnRNP K) regulates thymidine phosphorylase (TP) mRNA stability. The aim of the present study was to analyze hnRNP K and TP expression in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic and therapeutic potential of these two markers.', \"We analyzed hnRNP K and TP expression immunohistochemically in 121 clinically proven NPC cases. Statistical analyses were applied to correlate cytoplasmic hnRNP K with elevated TP expression and determine the prognostic significance of these parameters. The therapeutic implication of elevated TP expression was determined by measuring sensitivity of NPC cells to the TP-targeting drug, 5-fluoro-5'-deoxyuridine (5'-DFUR).\", \"There was a high correlation between cytoplasmic hnRNP K and high TP (P < 0.001). Both cytoplasmic hnRNP K and high TP were associated with poor overall survival (OS; P = 0.007 and P < 0.001, respectively) and distant metastasis-free survival (P = 0.003 and 0.001, respectively) of NPC patients. A multivariate analysis confirmed that both cytoplasmic hnRNP K and high TP are independent prognostic predictors for OS (P = 0.020 and 0.010, respectively). NPC cells expressing high TP were more sensitive to treatment with the TP-targeting drug, 5'-DFUR.",
            "output": [
                "Are heterogeneous ribonucleoprotein k and thymidine phosphorylase independent prognostic and therapeutic markers for nasopharyngeal carcinoma?"
            ]
        },
        {
            "id": "task847-55ed68de7ab6421b965ccf98090989b6",
            "input": "The association hepatocyte growth factor receptor (Met) tyrosine kinase with prognosis and survival in colon cancer is unclear, due in part to the limitation of detection methods used. In particular, conventional chromagenic immunohistochemistry (IHC) has several limitations including the inability to separate compartmental measurements. Measurement of membrane, cytoplasm, and nuclear levels of Met could offer a superior approach to traditional IHC.', \"Fluorescent-based IHC for Met was done in 583 colon cancer patients in a tissue microarray format. Using curvature and intensity-based image analysis, the membrane, nuclear, and cytoplasm were segmented. Probability distributions of Met within each compartment were determined, and an automated scoring algorithm was generated. An optimal score cutpoint was calculated using 500-fold crossvalidation of a training and test data set. For comparison with conventional IHC, a second array from the same tissue microarray block was 3,3'-diaminobenzidine immunostained for Met.\", \"In crossvalidated and univariate Cox analysis, the membrane relative to cytoplasm Met score was a significant predictor of survival in stage I (hazard ratio, 0.16; P = 0.006) and in stage II patients (hazard ratio, 0.34; P < or = 0.0005). Similar results were found with multivariate analysis. Met in the membrane alone was not a significant predictor of outcome in all patients or within stage. In the 3,3'-diaminobenzidine-stained array, no associations were found with Met expression and survival.",
            "output": [
                "Is the relative distribution of membranous and cytoplasmic met a prognostic indicator in stage I and II colon cancer?"
            ]
        },
        {
            "id": "task847-87a4f508c5e6443ab88105b8d3ca21d8",
            "input": "To study the mechanism of bortezomib resistance in JurkatB lines derived from T-lymphoblastic lymphoma/leukemia Jurkat line.', 'Cytotoxicities of popular chemotherapeutic drugs to JurkatB cells were analyzed by trypan blue assay. Functional drug efflux in JurkatB cells was determined by flow cytometry utilizing daunorubicin and the expression of P-glycoprotein (P-gp) was detected by Western blot. mRNA expression levels of proteasome beta5 subunit (PSMB5) were measured by quantitation real-time reverse transcription polymerase chain reaction. In situ hybridization was performed to detect the amplification of PSMB5 gene. The chymotrypsin-like activities were assayed by measuring the release of the fluorescent 7-amido-4-methylcoumarin (AMC) from the substrate N-succinyl-Leu-Leu-Val-Tyr-AMC. Cytogenetic studies were performed using R-banded metaphases and fluorescence in situ hybridization (FISH) analysis. IkappaB-alpha levels were detected by Western blot.', 'No cross-resistance to daunorubicin, adriamycin, vindesine, and etoposide was found in JurkatB cells. No evidence of drug efflux was found in JurkatB cells and the expression of P-gp was negative. The PSMB5 mRNA was overexpressed in highly resistant JurkatB5 and JurkatB1 lines compared with parental Jurkat, corresponding well with the increase of chymotrypsin-like activity and a karyotype of i(14q). Amplification of PSMB5 gene was demonstrated by in situ hybridization and FISH. The decreased IkappaB-alpha level in JurkatB5 cells after bortezomib treatment indicating an upregulation of nuclear factor-kappaB (NF-kappaB) activity.",
            "output": [
                "Does overexpression of the PSMB5 gene contribute to bortezomib resistance in T-lymphoblastic lymphoma/leukemia cells derived from Jurkat line?"
            ]
        },
        {
            "id": "task847-cf9fb5f180f14b91b80e0cd79e0e3546",
            "input": "The atherosclerotic process progresses more dynamically in hemodialysis (HD) patients than in the general population. In HD patients, lower magnesium levels were reported to be associated with increased atherosclerosis of the common carotid artery. We tested the hypotheses that magnesium supplementation helps to improve carotid intima media thickness (IMT) in HD patients.', 'A total of 47 patients on HD were included in the study. Patients were randomly divided into two groups: group A (Mg group), in which patients were given magnesium citrate orally at a dosage of 610 mg every other day for 2 months and group B (control group), in which patients received only calcium acetate therapy as a phosphate binder. At baseline and 2 months later, all patients underwent a carotid artery ultrasound scan to measure carotid IMT.', 'At the end of 2 months, mean serum calcium, phosphorus, and calcium x phosphorus product were not changed in both groups. As expected, mean serum Mg level significantly increased in the Mg group at the end of 2 months. In addition, serum parathyroid hormone (PTH) level significantly decreased in the Mg group at the end of 2 months (P = 0.003). Baseline carotid IMT was similar between the groups. Bilateral carotid IMT was significantly improved in patients treated with magnesium citrate compared to initial values (P = 0.001 for left, P = 0.002 for right).",
            "output": [
                "Does magnesium supplementation help to improve carotid intima media thickness in patients on hemodialysis?"
            ]
        },
        {
            "id": "task847-08975825b9f942c48e9a7f94be090c70",
            "input": "Event-related potentials (ERPs) are sensitive measures of both perceptual and cognitive processes. The aim of the present study was to identify brain regions involved in the processes of cognitive dysfunction in narcolepsy by means of ERP tomography.', 'In 17 drug-free patients with narcolepsy and 17 controls, ERPs were recorded (auditory odd-ball paradigm). Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components. Psychometry included measures of mental performance, affect and critical flicker fusion frequency (CFF).', 'In the ERPs patients demonstrated delayed cognitive N2 and P300 components and reduced amplitudes in midline regions, while N1 and P2 components did not differ from controls. LORETA suggested reduced P300 sources bilaterally in the precuneus, the anterior and posterior cingulate gyri, the ventrolateral prefrontal cortex and the parahippocampal gyrus. In psychometry, patients demonstrated deteriorated mood, increased trait anxiety, decreased CFF and a trend toward reduced general verbal memory and psychomotor activity.",
            "output": [
                "Does event-related-potential low-resolution brain electromagnetic tomography ( ERP-LORETA ) suggest decreased energetic resources for cognitive processing in narcolepsy?"
            ]
        },
        {
            "id": "task847-396fe39d45b54897b184b6a8e0b1a90c",
            "input": "To evaluate whether genotypes of interleukin (IL)-6 gene promoter positions -174 and -572 are associated with histologic chorioamnionitis and neonatal inflammatory disease in preterm infants.', 'DNA from very low birth weight or very preterm infants (n = 107) was genotyped for IL-6-174 and -572 polymorphisms (GG/GC/CC). The placentas were analyzed for histological inflammatory findings. Data on neonatal inflammatory diseases, including chronic lung disease (CLD), necrotizing enterocolitis (NEC), and septicemia, were collected using the definitions of the Vermont Oxford Network database.', 'In univariate analyses, the IL-6-174 GG genotype was associated with a higher incidence of histologic chorioamnionitis. In multivariate analyses, the -174 GG and -572 GC genotypes were correlated with histologic chorioamnionitis (P = .039 and .009, respectively). Gestational age was not associated with genotype polymorphisms. IL-6-174 genotypes were not associated with CLD and/or NEC, but the CC genotype was correlated with septicemia in both univariate and multivariate analyses (P = .027). IL-6-572 genotypes were not associated with neonatal inflammatory disease.",
            "output": [
                "Is interleukin-6 polymorphism associated with chorioamnionitis and neonatal infections in preterm infants?"
            ]
        },
        {
            "id": "task847-89025ca4411f45618e10f6f390f089d4",
            "input": "Experimental trials using test meals suggest that water promotes satiety and decreases subsequent intake, thus possibly working to prevent obesity, when it is consumed as an integral component of a food, but not when consumed alone or alongside a food. We examined the associations of intake of water from beverages and intake of water from foods with body mass index (BMI) and waist circumference in free-living humans consuming self-selected diets.', 'This observational cross-sectional study included 1136 female Japanese dietetic students 18-22 y of age. Dietary intake was assessed with a validated, self-administered, comprehensive, diet-history questionnaire. BMI was calculated using measured body height and weight. Waist circumference was measured at the level of the umbilicus.', 'Means +/- standard deviations of BMI, waist circumference, intake of water from beverages, and intake of water from foods were 21.3 +/- 2.7 kg/m(2), 72.9 +/- 7.1 cm, 569 +/- 318 g/1000 kcal, and 476 +/- 110 g/1000 kcal, respectively. After adjustment for potential confounding factors, intake of water from beverages was not associated with BMI (P for trend = 0.25) or waist circumference (P for trend = 0.43). Conversely, intake of water from foods showed independent and negative associations with BMI (P for trend = 0.030) and waist circumference (P for trend = 0.0003).",
            "output": [
                "Is intake of water from foods , but not water from beverages , related to lower body mass index and waist circumference in free-living humans [ corrected ]?"
            ]
        },
        {
            "id": "task847-4bea74b808bb4f0eaf7c0110be4c2d26",
            "input": "Vasopeptidase inhibitors are drugs that inhibit angiotensin-converting enzyme and neutral endopeptidase (NEP). The latter is a protease that degrades vasoactive peptides and is increased in diabetes. We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with AVE7688, a vasopeptidase inhibitor, improves neurovascular and neural function. In this study, we determined the effect of treating Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes, with AVE7688 on vascular and neural function.', 'ZDF rats at 12 weeks of age were treated for 12 weeks with AVE7688 (500 mg/kg diet). Afterwards, vascular reactivity of epineurial arterioles of the sciatic nerve and nerve conduction velocity and blood flow was determined.', 'Vascular and neural function was significantly impaired in ZDF rats compared with age-matched lean (control) rats. Treating ZDF rats with AVE7688 improved vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Motor and sensory nerve conduction velocity, endoneurial blood flow and thermal nociception end-points were also improved by treatment compared with untreated ZDF rats. Superoxide and expression of NEP were increased in epineurial arterioles from ZDF rats and attenuated by treatment with AVE7688.",
            "output": [
                "Does treatment of Zucker diabetic fatty rats with AVE7688 improve vascular and neural dysfunction?"
            ]
        },
        {
            "id": "task847-146c4513aaeb473aa647a3b7c9e7b498",
            "input": "To explore the effect of artesunate (ART) on cell differentiation and cell cycle distribution of the prostate cancer cell line PC-3 in vitro.', 'PC-3 cells were cultivated with ART from logarithmic growth phase. After 48-hour treatment, the cell cycles were detected by flow cytometry (FCM), and enzyme linked immunosorbent assay was used to detect the level of prostate specific antigen (PSA) in cell culture supernatant. The change of cellular morphology was observed under a transmission electron microscope (TEM).', 'In comparison with the blank control group, the rate of G(0)/G(1) plus S stages of PC-3 cells was significantly decreased in the high-dose ART group. The PC-3 cell was arrested in G(2)/M by ART. The rates of G(2)/M of the high-dose ART group and the medium-dose ART group were obviously higher than those of the blank control group and the cisplatin group (P<0.05). The levels of PSA in the three ART groups were significantly lower than that of the normal control group (P<0.05, P<0.01). In the ART groups, TEM showed that some vacuoles appeared in endochylema, cell polarity was enhanced, cell nucleus leaned to one side of the cell, and microvilli increased on the other side of the cell.",
            "output": [
                "Does [ Artesunate induce prostate cancer cell line PC-3 differentiation and cell cycle arrest ]?"
            ]
        },
        {
            "id": "task847-efd07b03568c49cbb560db22b480cddf",
            "input": "Vascular pathology is associated with reduced performance on neuropsychological tests, particularly in older adults. A likely explanation involves a disruption in the blood brain barrier (BBB). Work from clinical samples show alterations in BBB function is associated with cognitive dysfunction on testing, though no study has examined this possibility in healthy older adults.', '35 older adults, without significant neurological or psychiatric history, underwent fasting blood draw and neuropsychological testing. Serum levels of S100beta were quantified to provide a measure of BBB function.', 'Partial correlations showed S100beta levels were inversely related to performance in multiple cognitive domains, including memory (r = 0.43, p = 0.02), psychomotor speed and visual attention (r = 0.37, p = 0.05), and working memory (r = -0.48, p = 0.008).",
            "output": [
                "Is increased S100beta associated with reduced cognitive function in healthy older adults?"
            ]
        },
        {
            "id": "task847-ddded209e103419f82f6f33a7f558101",
            "input": "Two different forms of vulvar intraepithelial neoplasia (VIN) are recognised: (1) usual-type (bowenoid) VIN, which is related to high-risk papillomavirus infection, and (2) differentiated (simplex) VIN, which is associated with chronic inflammation. The aim of this study was to investigate the presence of chromosome 3q26 gains in the spectrum of precancerous lesions and invasive squamous cell carcinomas (SCCs) of the vulva.', '3q26 gains were analysed using fluorescence in situ hybridisation in a series of usual-type VINs, VINs of the differentiated type and invasive squamous cell carcinomas. In addition, all cases were examined for human papillomavirus (HPV) DNA, p53 mutations, and p16 and p53 protein expression.', 'Gains of chromosome 3q26 were present in all VINs of the differentiated type and in 50% of the usual-type VIN lesions. 81% of SCCs were positive for 3q26 gains irrespective of the HPV status and of the associated precursor lesion. HPV-associated lesions exhibited the typical, strong cytoplasmic p16 accumulation while mutated p53 was only detected in HPV-negative VINs or SCCs, and was associated with an overexpression of p53 protein.",
            "output": [
                "Are gains of chromosome region 3q26 in intraepithelial neoplasia and invasive squamous cell carcinoma of the vulva frequent and independent of HPV status?"
            ]
        },
        {
            "id": "task847-60d2b853f8464e0eaed29bb83be57786",
            "input": "To evaluate the association of HLA-B51 and ocular involvement in Adamantiades-Beh\u00e7et's disease.\", \"We retrospectively analysed all patients with Adamantiades-Beh\u00e7et's disease examined in our Department of Ophthalmology since 1982. All patients fulfilled the criteria of the International Study Group for Beh\u00e7et's disease. We included 140 patients (63 female and 77 male) with a mean follow-up of 6.4 years.\", 'The mean age at the first manifestation was 23 years; full disease was noted at 32 years. The mean age at the time of eye involvement was 30 years. Most of the patients were of Turkish (n=73) or German (n=34) origin. A total of 56% patients developed eye involvement. Forty-nine out of 76 HLA-B51-positive patients (64.5%) and 26 out of 60 HLA-B51-negative patients (43.3%; P=0.014) developed ocular involvement.",
            "output": [
                "Is ocular involvement associated with HLA-B51 in Adamantiades-Beh\u00e7et 's disease?"
            ]
        },
        {
            "id": "task847-0f696e5928d54767b79f817e02a9e64d",
            "input": "The aim of this study was to assess the effect of the implementation of evidence-based guidelines and subsequent feedback to surgeons in the management of acute pancreatitis.', 'An evidence-based Pancreatitis Proforma was developed. Data were prospectively recorded (01/06/2005-30/09/2007). Audit feedback (AFB) was performed at 9 months. A final analysis was performed comparing outcomes pre- and post-audit feedback.', '372 patients were included. Median age (range) was 57 (12-96) years. 168 (45.2%) patients were admitted pre-AFB. Post-AFB, there was a significant increase in the number of patients whose diagnosis was made within 48 hours (135/168 (80.4%) vs 189/204 (92.6%), p<0.001) and who underwent definitive treatment for mild biliary pancreatitis (33/61 (54.1%) vs 56/70 (80.0%), p=0.002). Post-AFB there was also a significant reduction in the number of computed tomography (CT) scans performed for patients with mild acute pancreatitis (23/85 (27.1%) vs 13/99 (13.1%), p=0.018). Mortality (9/168 (5.4%) vs 3/204 (1.4%), p=0.040) also decreased. On multivariate analysis, AFB was an independent factor for change in the use of CT scans (p=0.015) and management of patients with mild biliary pancreatitis (p=0.039).",
            "output": [
                "Is closing the audit loop necessary to achieve compliance with evidence-based guidelines in the management of acute pancreatitis?"
            ]
        },
        {
            "id": "task847-ac178ee6a1b74fd2b056f6d45abb0d33",
            "input": "Activation of NF-kappaB signaling pathway plays a critical role in the initiation and progression of carcinogenesis. However, the role of NF-kappaB pathway in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. Studies have shown that curcumin possesses anti-infection and anti-oxidation effects. This study was to evaluate whether curcumin could induce apoptosis through inhibition of NF-kappaB signaling pathway in ESCC cells.', 'Expressions of pIkappaBalpha and Bcl-2 were detected using Western blott after incubation of ESCC cells with curcumin (50 micromol/L) at different time points. Apoptosis and the number of viable ESCC cells were analyzed using flow cytometry and MTT, respectively, after the treatment of curcumin, 5-FU, or the combination of curcumin and 5-FU.', 'In two ESCC cell lines, EC9706 and Eca109,curcumin inhibited IkappaBalpha phosphorylation and Bcl-2 in a time-dependent manner; curcumin alone increased cell apoptosis (P<0.05), and the effect became more prominent when it was combined with 5-FU (P<0.05); curcumin plus 5-FU exerted a stronger inhibition effect on cell proliferation than curcumin alone (P<0.05) or 5-FU alone (P<0.05).",
            "output": [
                "Does [ Curcumin promote apoptosis of esophageal squamous carcinoma cell lines through inhibition of NF-kappaB signaling pathway ]?"
            ]
        },
        {
            "id": "task847-c98b373733bc4212bf274443d4e4436a",
            "input": "Left ventricular hypertrophy (LVH) is common in dialysis patients, and an independent predictor of mortality. While recent studies have shown no differences in mortality between the two most common dialysis modalities, hemodialysis (HD) and peritoneal dialysis (PD), their impact on LVH is controversial. We thus performed cardiac ultrasound studies in prevalent dialysis patients receiving either HD or PD and compared LVH.', 'We included 48 HD and 62 PD patients receiving treatment for at least three months in our dialysis center. All patients underwent echocardiographic examination and blood pressure measurements immediately following therapy. Volume status was assessed by bioelectrical impedance analysis.', 'There was no baseline difference in demographics or comorbidities between HD and PD patients. As expected, extracellular water (ECW) in post-HD patients was significantly lower than that in pre-HD and PD patients, while cardiac output (CO) and systolic blood pressure (SBP) were higher in pre-HD than that in post-HD or PD patients. There was no significant difference in CO or SBP between post-HD and PD patients. Left ventricular mass index (LVMI) was markedly higher in HD patients as compared to PD patients. Thus, the prevalence of LVH according to the Framingham criteria was 68.8% in HD patients and 45.2% in PD patients. Subgroup analysis showed similar results in the patients who had been on single-modality dialysis for at least two years and in the anuric patients. Finally, in a linear regression model (r(2) = 0.364, p < 0.001), SBP, treatment modality (to be in HD), and ECW were all independent predictors of LVMI.",
            "output": [
                "Is the prevalence of left ventricular hypertrophy in Chinese hemodialysis patients higher than that in peritoneal dialysis patients?"
            ]
        },
        {
            "id": "task847-ea7bb52068284f49a2eb6c3c9a382723",
            "input": "While autogenous arteriovenous access is preferred, prosthetic arteriovenous grafts (AVG) are still required in a large number of patients. Infection of AVGs occurs frequently and may cause life-threatening bleeding or sepsis. Multiple treatment strategies have been advocated (ranging from graft preservation to excision with complex concomitant reconstructions), indicating a lack of consensus on appropriate management of infected AVGs. We undertook this study to evaluate if, in the setting of anastomotic involvement, brachial artery ligation distal to the origin of the deep brachial artery accompanied by total graft excision (BAL) is safe and effective.', 'All prosthetic arteriovenous graft infections managed by a single surgeon between 1995 and 2006 were reviewed retrospectively. Patients were identified from a computerized vascular registry, and data were obtained via patient charts and the electronic medical record.', 'We identified 45 AVG infections in 43 patients. Twenty-one patients (49%) demonstrated arterial anastomotic involvement and were treated with BAL; these form the cohort for this analysis. Mean patient age was 53.2 (SD 9.5) years. The primary etiologies for end stage renal disease (ESRD) were hypertension (29%), HIV (24%), and diabetes (19%). An upper arm AVG was present in 95% of patients; one (5%) had a forearm AVG. The majority of grafts were polytetrafluoroethylene (PTFE) (90%). Follow-up was 100% at 1 month, 86% at 3 months, and 67% at 6 months. No ischemic or septic complications occurred in the 21 patients who underwent BAL.",
            "output": [
                "Is brachial artery ligation with total graft excision a safe and effective approach to prosthetic arteriovenous graft infections?"
            ]
        },
        {
            "id": "task847-06ef3d6340164f35956d42effdb63f66",
            "input": "Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage III colon cancer who are more likely to benefit from adjuvant chemotherapy. The present study analyzed a subset of 10 polymorphisms within eight genes involved in the tumor angiogenesis pathway and their impact on prognosis in stage III colon cancer patients treated with adjuvant chemotherapy.', \"Blood samples were obtained from 125 patients with locally advanced colon cancer at University of Southern California medical facilities. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism and 5'-end [gamma-(33)P] ATP-labeled PCR protocols.\", 'Polymorphisms in vascular endothelial growth factor (VEGF) (C+936T; P = 0.003, log-rank test) and interleukin-8 (IL-8) (T-251A; P = 0.04, log-rank test) were independently associated with risk of recurrence in stage III colon cancer patients. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of VEGF C+936T and IL-8 T-251A were associated with a higher likelihood of developing tumor recurrence (P < 0.001).",
            "output": [
                "Do polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer?"
            ]
        },
        {
            "id": "task847-8d9033a32e7b4bb9b8e28fbb62e15c4e",
            "input": "We examined whether the presence and extent of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) predict adverse outcomes in nonischemic cardiomyopathy (NICM) patients.', 'Morbidity and mortality is high in NICM patients. However, the clinical course of an individual patient is unpredictable and current risk stratification approaches are limited. Cardiovascular magnetic resonance detects myocardial fibrosis, which appears as LGE after contrast administration and may convey prognostic importance.', 'In a prospective cohort study, 65 NICM patients with left ventricular (LV) ejection fraction < or =35% underwent CMR before placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death. The CMR images were analyzed for the presence and extent of LGE and for LV function, volumes, and mass. Patients were followed for an index composite end point of 3 cardiac events: hospitalization for heart failure, appropriate ICD firing, and cardiac death.', 'A total of 42% (n = 27) of patients had CMR LGE, averaging 10 +/- 13% of LV mass. During a 17-month median follow-up, 44% (n = 12) of patients with LGE had an index composite outcome event versus only 8% (n = 3) of those without LGE (p < 0.001 for Kaplan-Meier survival curves). After adjustment for LV volume index and functional class, patients with LGE had an 8-fold higher risk of experiencing the primary outcome (hazard ratio 8.2, 95% confidence interval 2.2 to 30.9; p = 0.002).",
            "output": [
                "Does late gadolinium enhancement by cardiovascular magnetic resonance herald an adverse prognosis in nonischemic cardiomyopathy?"
            ]
        },
        {
            "id": "task847-1f536a07b4bc4ca38751ad5b4bc1a195",
            "input": "The aim of this study was to assess the relationship between cardiomyopathy and recipient twin (RT) outcome in twin-twin transfusion syndrome (TTTS).', 'Fetal echocardiography and outcomes data in 62 consecutive pregnancies with TTTS were reviewed. The primary outcome was neonatal RT survival. The severity of RT cardiomyopathy at presentation was assessed by the cardiovascular profile score (CVPS). RT outcomes and odds of survival were compared between groups stratified by CVPS.', 'Overall neonatal survival for all fetuses was 61% (76 of 124). RT survival was 58% (36 of 62). Grouped by CVPS, RT survival was greater (50%) for those with CVPS > or = 9 and even higher (74%) for CVPS of 10. Among the components of the CVPS, atrioventricular valve regurgitation was associated with negative RT outcome. Other factors at presentation were not predictive of RT outcome.",
            "output": [
                "Does initial fetal cardiovascular profile score predict recipient twin outcome in twin-twin transfusion syndrome?"
            ]
        },
        {
            "id": "task847-8b5268c2ed82461f8e403eb2aa4e2463",
            "input": "To determine the prevalence of Raynaud's phenomenon (RP) in patients with primary Sjogren's syndrome (pSS) and to identify clinical and immunological characteristics associated with this manifestation. Since increased interferon-gamma (INF-gamma) has been associated with RP, we also compared the INF-gamma production in pSS patients with or without RP.\", 'RP was diagnosed if pSS patients presented with characteristic sequence of skin color changes of the digits. In uncertain cases noninvasive vascular tests were performed by ultrasound examination. The secretion of INF-gamma by peripheral blood mononuclear cells was assessed by enzyme-linked immunospot analysis. Further, we examined the expression of different lymphocyte activation markers (CD25, CD45RO, CD69) on CD4+ T-cells by flow cytometric analysis.', 'Thirty-six of 108 patients with pSS had RP. In these patients we found a significantly increased number of INF-gamma-secreting peripheral blood mononuclear cells compared with patients without RP or to healthy controls. Further, in patients with RP a significantly increased percentage of CD25-positive T-helper cells was detectable. In addition we found an association of leukopenia, thyroiditis, and lower C3 levels with RP in pSS patients.",
            "output": [
                "Is interferon-gamma increased in patients with primary Sjogren 's syndrome and Raynaud 's phenomenon?"
            ]
        },
        {
            "id": "task847-df41ea25bb4c4bf3b00ec9dfe7c73089",
            "input": "Atherosclerosis is the underlying pathological process of most cardiovascular disease. Thrombin is a serine protease which can activate protease activated receptors (PAR) on vascular smooth muscle cells (VSMC) to elicit cellular responses that can contribute to the pathogenesis of atherosclerosis. Human atherosclerosis commences with the binding and retention of lipoproteins by the glycosaminoglycan (GAG) chains of chondroitin/dermatan sulfate proteoglycans. The potential effects of thrombin on the synthesis and structure of CS/DS proteoglycans produced by VSMCs was investigated.', 'VSMCs were derived from human internal mammary arteries. Proteoglycan synthesis was assessed by [(35)S]sulfate and [(3)H]glucosamine incorporation. Proteoglycan size was assessed by SDS-PAGE and size exclusion chromatography.",
            "output": [
                "Does thrombin regulate vascular smooth muscle cell proteoglycan synthesis via PAR-1 and multiple downstream signalling pathways?"
            ]
        },
        {
            "id": "task847-fb3ac4682b994530a68bf3858ca92634",
            "input": "The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P-450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to determine whether their expression profile in localized infiltrative breast cancer is associated with an increased risk of recurrent disease.', 'Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochemistry and Western-blot analysis.', 'Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 months showed nuclear location of hPXR isoform 2. This location was associated with the nuclear immunoexpression of RXR-alpha.",
            "output": [
                "Is human pregnane X receptor expressed in breast carcinomas , potential heterodimers formation between hPXR and RXR-alpha?"
            ]
        },
        {
            "id": "task847-a825c7c1a32545689837f68ca0f1e788",
            "input": "In the nonobese diabetic (NOD) mouse model of Sj\u00f6gren's syndrome, lymphocytic infiltration is preceded by an accumulation of dendritic cells in the submandibular glands (SMGs). NOD mice also exhibit an increased frequency of mature, fractalkine receptor (CX3C chemokine receptor [CX3CR]1) expressing monocytes, which are considered to be precursors for tissue dendritic cells. To unravel further the role played by fractalkine-CX3CR1 interactions in the salivary gland inflammation, we studied the expression of fractalkine in NOD SMGs.\", 'We studied protein expression using Western blot analysis of whole tissue lysates. Protease activity was measured in salivary gland tissue lysates using fluorimetric substrates. Digestive capacity of enzymes was determined by in vitro incubation of recombinant enzyme and fractalkine, followed by protein staining and Western blot.', 'Fractalkine was detected in salivary glands of both NOD and control mice at all ages. Western blot analysis showed fractalkine cleavage with increasing age, which was more pronounced in NOD mice. This cleavage resulted in a decrease in the 31 kDa form of the protein, and the generation of an approximately 19 kDa band. Furthermore, in NOD animals older than 15 weeks, we noted the presence of a unique approximately 17 kDa fragment. This cleavage was organ specific, because it did not occur in brain or pancreas. Increased gelatinase and alpha-secretase activity were detected in NOD SMG and contributed to cleavage of the 31 kDa protein. Because aberrant cleavage products may induce autoimmunity, we studied the presence of autoantibodies against fractalkine. Indeed, NOD mice exhibited significantly more antibodies against fractalkine than did control animals.",
            "output": [
                "Does altered fractalkine cleavage potentially promote local inflammation in NOD salivary gland?"
            ]
        },
        {
            "id": "task847-6ab62231da7d4dc9899c20fcf1f3929f",
            "input": "Gut ischemia may prime neutrophils to produce an exaggerated inflammatory response when challenged with bacterial pathogens. Secretory immunoglobulin A (sIgA) is the first line of defense against potential pathogens, but may also exert its anti-inflammatory effects on potentially destructive neutrophil functions. We hypothesized that sIgA would blunt the gut-mediated priming events that lead to neutrophil hypersensitivity to bacterial challenge.', 'Confluent Caco2 cell monolayers were grown in a two-chamber culture system under normoxic or hypoxic conditions for 90 minutes followed by a 90-minute reoxygenation period. sIgA was placed in apical chamber media in experimental groups before reoxygenation period. Supernatants were then collected and incubated with neutrophils. Lipopolysaccharide was then used to activate neutrophils. Measurements of CD11b expression, elastase and superoxide anion production, and chemotaxis were undertaken.', 'Polymorphonuclear neutrophils (PMNs) treated with Caco2 cells undergoing hypox-reoxygenation followed by activation with lipopolysaccharide show a dramatic increase in inflammatory potential when compared with na\u00efve neutrophils (n = 4, *p < 0.001). The addition of sIgA in this same group before the activation step showed a blunting of the inflammatory response, but never to the level of na\u00efve PMN.",
            "output": [
                "Does secretory immunoglobulin a blunt gut-mediated priming of neutrophils in vitro?"
            ]
        },
        {
            "id": "task847-f1acad2ef73d43b29b62045bdb14cee4",
            "input": "Hepatic expression of growth hormone (GH)-inducible genes serine protease inhibitor (Spi 2.1) and insulin-like growth factor (IGF)-I are inhibited by interleukin (IL)-1. The current study examines the role of the nuclear factor kappaB (NFkappaB) pathway and suppressor of cytokine signaling (SOCS)-3 expression as potential mechanisms for IL-1-mediated GH resistance.', 'CWSV-1 hepatocytes were cotransfected with Spi 2.1 or IGF-1 promoter luciferase constructs and empty pCMV4 vector or dominant negative inhibitor-kappaBalpha (IkappaBalpha)S/A construct. Cells were treated with or without IL-1 and then stimulated with or without recombinant human GH. Cell extracts were assayed for luciferase activity and protein, normalized and expressed as fold-induction. CWSV-1 cells transfected with pCMV4 or IkappaBalphaS/A were treated with or without IL-1 then SOCS-3 mRNA was measured. Finally, CWSV-1 cells were cotransfected with a SOCS-3 promoter construct with or without pCMV4 or IkappaBalphaS/A and then stimulated with or without IL-1 to investigate SOCS-3 promoter activity.', 'CWSV-1 cells cotransfected with pCMV4 demonstrated a three- to fivefold induction of Spi 2.1 or IGF-1 promoter activity after GH stimulation that was almost completely inhibited by IL-1. Cotransfection with IkappaBalphaS/A increased GH-inducible Spi 2.1 and IGF-1 promoter activity, but the inhibitory effects of IL-1 on both promoters were attenuated by cotransfection with IkappaBalphaS/A. IL-1 stimulated SOCS-3 mRNA expression and promoter activity. Cotransfection with IkappaBalphaS/A increased IL-1-inducible SOCS-3 promoter activity, but not SOCS-3 mRNA or protein.",
            "output": [
                "Does nuclear factor kappaB mediate the inhibitory effects of interleukin-1 on growth hormone-inducible gene expression?"
            ]
        },
        {
            "id": "task847-2bf09ed2d5e64efebee6755c4ba2e7b0",
            "input": "Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity.', 'We analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced.', 'Nine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients.",
            "output": [
                "Is a polymorphism of EGFR extracellular domain associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment?"
            ]
        },
        {
            "id": "task847-ac89126e72184920a0d4a0d5ed72e914",
            "input": "To test whether an acute transfusion practice of packed red blood cells (pRBC) : fresh-frozen plasma (FFP) 1 : 1 would be associated with reduced mortality in acute bleeding multiply injury.', 'Retrospective analysis using the TR-DGU database (Trauma Registry of the Deutsche Gesellschaft f\u00fcr Unfallchirurgie 2002-2006) on primary admissions with substantial injury (Injury Severity Score > 16) and massive transfusion (> 10 pRBCs). Seven hundred thirteen patients were divided into three groups according to the pRBC : FFP ratio transfused, that is, (i) pRBC : FFP > 1.1; (ii) pRBC : FFP 0.9-1.1 (1 : 1); and (iii) pRBC : FFP < 0.9, and mortality rates were compared.', 'Four hundred ninety-seven (69.7%) of patients were male, the mean age was 40.1 (+/- 18.3) years. Injury characteristics and pathophysiological state upon emergency room arrival were comparable between groups. Out of 713, 484 patients had undergone massive transfusion with pRBC : FFP > 1.1, 114 with pRBC : FFP 0.9-1.1 (1 : 1), and 115 with pRBC : FFP < 0.9 ratios. Acute mortality (< 6 h) rates for pRBC : FFP > 1.1, pRBC : FFP 0.9-1.1 (1 : 1), and pRBC : FFP < 0.9 ratios were 24.6, 9.6 and 3.5% (P < 0.0001), 24-h mortality rates were 32.6, 16.7 and 11.3% (P < 0.0001), and 30-day mortality rates were 45.5, 35.1 and 24.3% (P < 0.001). The frequency for septic complications and organ failure was higher in the pRBC : FFP 0.9-1.1 (1 : 1) group, ventilator days and length of stays for intensive care unit and overall in-hospital were highest in the pRBC : FFP < 0.9 ratio group (P < 0.0005).",
            "output": [
                "Are red-blood-cell to plasma ratios transfused during massive transfusion associated with mortality in severe multiple injury : a retrospective analysis from the Trauma Registry of the Deutsche Gesellschaft f\u00fcr Unfallchirurgie?"
            ]
        },
        {
            "id": "task847-ff4126990d584a0785bde855a74f8de7",
            "input": "Most astigmats have a similar level of astigmatism in each eye. However, there is controversy over whether the astigmatic axes in fellow eyes typically show direct or mirror symmetry. We carried out a statistical analysis designed to address this issue.', \"The median absolute difference in the astigmatic axes of fellow eyes was calculated for a sample of 50 995 astigmats (subjects with at least 0.25 D of astigmatism in each eye). This was done, firstly, for a 'direct symmetry model' in which the difference in axis was calculated as |AxisR - AxisL| and secondly, for a 'mirror symmetry model' in which the difference in axis was calculated as |AxisR - (180 - AxisL)|.\", 'Under the direct symmetry model, the median absolute difference in the axis of astigmatism between fellow eyes was 20 degrees. Under the mirror symmetry model, the median absolute difference in the axis of astigmatism between fellow eyes was significantly lower, at 10 degrees (p < 10e-100). Comparable results were found when the analysis was restricted to subjects with: lower levels of astigmatism (< or =1.00 D), higher levels of astigmatism (>1.00 D), against-the-rule astigmatism, with-the-rule astigmatism or oblique astigmatism (all p < 10e-100).",
            "output": [
                "Do axes of astigmatism in fellow eyes show mirror rather than direct symmetry?"
            ]
        },
        {
            "id": "task847-c376ca0d15de4134a98061f51d61c4a4",
            "input": "The putative role of sulfur amino acids such as homocysteine (tHcy) as cardiovascular risk factors is controversial in chronic kidney disease (CKD). Although, S-adenosylhomocysteine (SAH) levels have been linked to CVD in non-renal populations, such relationship has not been evaluated in CKD.', 'Serum concentrations of S-adenosylmethionine (SAM), SAH and total homocysteine (tHcy) were determined by HPLC in 124 CKD stage 5 patients (GFR range 1-11 m/min) and 47 control subjects, and related to renal function, presence of CVD, inflammation and protein-energy wasting (PEW).', 'The levels of SAM and SAH were higher in CKD patients than in controls. Both SAM (rho=-0.19; P<0.05) and SAH (rho=-0.37, P<0.001) were inversely related to GFR. The concentrations of SAH were significantly higher (P<0.001) in patients with CVD than in non-CVD patients, (683 (201-3057) vs 485 (259-2620) nmol/L; median (range)) as opposed to tHcy levels, which were lower in CVD patients. While SAH was not associated with the presence of inflammation or PEW, it was a significant contributor (OR; 4.9 (CI 1.8-12.8), P<0.001) to CVD in a multinomial logistic regression model (pseudo r(2)=0.31).",
            "output": [
                "Are elevated serum levels of S-adenosylhomocysteine , but not homocysteine , associated with cardiovascular disease in stage 5 chronic kidney disease patients?"
            ]
        },
        {
            "id": "task847-b23d7bd4734a4e888440bb4eb57702a2",
            "input": "Circulation on blood extracorporeally through plastic tubing activates several pathways including systemic inflammation and oxidative stress. These phenomena are suspected to participate to neurological and cardiovascular side effects observed in the patients under cardiopulmonary bypass (CPB). A direct relationship, in diabetic patients, between hyperglycemia and morbidity and mortality has been established. However, it is still unclear whether perioperative hyperglycemia has a direct effect on adverse events in cardiac surgery. The purpose of this study was to determine the influence of hyperglycemia on inflammation and oxidative stress in patients under CPB during cardiac surgery.', 'Control patients (n=17) and diabetic (type 2) patients (n=13) were included in this study. Blood samples were drawn before, during and after the CPB. Oxidative stress was evaluated in the plasma by direct and indirect approaches. Direct detection of ascorbyl radicals was assessed by electron spin resonance spectroscopy. An index: ascorbyl radical/vitamin C ratio is an indicator of the degree of oxidative stress taking place in the plasma. Oxygen radical absorbing capacity (ORAC) values were used as measurement of antioxidant capacity of the plasma. To determine inflammation profile of patients, we measure the evolution of plasma concentration of interleukin 8 (IL-8).', 'During cross clamping and post-CPB, the index ascorbyl radical/vitamin C is increased; the value of the index is more significant in diabetic patients. Concomitantly, ORAC values decreased in all the patients during cross clamping (p<0.05). Results concerning inflammatory index showed that IL-8 levels increased during the CPB.",
            "output": [
                "Is [ Oxidative stress exacerbated in diabetic patients during cardiopulmonary bypass ]?"
            ]
        },
        {
            "id": "task847-fa674f6e4d9144f18d7c4ccecbe9a17d",
            "input": "There is evidence that patients with bipolar disorder have working memory deficits even during periods of euthymia. The neural basis of such deficits and its relationship with genetic risk remain unclear. We utilized functional magnetic resonance imaging (fMRI) to investigate neural activity in samples of bipolar disorder patients and their unaffected first-degree relatives while performing working memory tasks of increasing difficulty.', 'Twenty remitted bipolar I disorder patients, 20 of their unaffected first-degree relatives, and 20 healthy volunteers were recruited and successfully completed scanning. Subjects participated in fMRI scans consisting of an n-back working memory task with three stages of increasing difficulty (1-back, 2-back, and 3-back), alternating with a baseline attention task. Groups were analyzed separately to produce brain activation maps, and a group-by-task analysis of variance (ANOVA) with post hoc comparisons was completed.', 'Patients performed more poorly online than control subjects and relatives on the 2-back and 3-back tasks. The group-by-task ANOVA demonstrated a significantly altered region of neural activity involving a cluster located in the left frontal pole/ventrolateral gyrus. Post hoc analyses demonstrated that this cluster was accounted for by significantly greater activation in relatives compared with control subjects for the 2-back task. Patients demonstrated a trend to significantly greater activation than control subjects in the same cluster during 1-back performance.",
            "output": [
                "Is genetic liability for bipolar disorder characterized by excess frontal activation in response to a working memory task?"
            ]
        },
        {
            "id": "task847-63463bee35314bf2aa6735ace4614c98",
            "input": "Alloreactive NK cells play a role in tumor eradication after allogeneic HLA mismatched stem cell transplantation (SCT). The effect of NK alloreactivity in HLA identical SCT is still under debate and in particular in transplantation for chronic myeloid leukemia (CML) the data are very limited and with conflicting outcome. The aim of our study was to evaluate the effect of KIR genes and KIR ligands on leukemia free survival (LFS) and relapse rate in a well-defined, homogeneous group of CML patients phase upon HLA identical sibling SCT.', 'We retrospectively analyzed the effect of KIRs and KIR ligands (C1 and C2) on LFS and relapse in 70 CML patients in 1st chronic phase, who had received an HLA identical sibling graft. For KIR typing we used a single PCR based KIR typing protocol that also included primers allowing for the identification of the KIR binding site on HLA-Cw (AA 77 and 80).', 'The data show clear differences in transplant outcome between patients having both ligands (C1 and C2) as compared to patients having only one ligand (C1 or C2). In the latter group, the stimulatory KIR2DS5 gene was associated with improved leukemia free survival (p=0.007; hazard ratio 4.3; 95% confidence interval 1.3-6.7) and lower relapse rates (p=0.028; HR 4.3, 95% CI 1.1-9.1). In contrast, in patients carrying both ligands, KIR2DS5 was associated with reduced LFS (p=0.0056; HR 0.3; 95% CI 0.1-0.7) and higher relapse rate (p=0.02; HR 0.35, 95% CI 0.1-0.8).",
            "output": [
                "Is kIR2DS5 associated with leukemia free survival after HLA identical stem cell transplantation in chronic myeloid leukemia patients?"
            ]
        },
        {
            "id": "task847-a7265f9847ef4f779549d2a5cc142c4d",
            "input": "It has been suggested that prostate specific antigen has no predictive value for prostate cancer after a first negative biopsy has been performed. We compared the performance operating characteristics of prostate specific antigen for prostate cancer between a first and subsequent prostate biopsy in a group of men with complete verification of cancer status.', 'From the 18,882 participants in the Prostate Cancer Prevention Trial we examined men in the placebo group who had only a first biopsy or a first and second prostate biopsy with a prostate specific antigen and digital rectal examination within 1 year before each biopsy. The receiver operating characteristic curve was estimated for prostate specific antigen for detection of prostate cancer on the first biopsy compared to the second, and the C-statistics were compared.', 'Of this group 5,608 men had a first biopsy and 687 of those with a negative first biopsy underwent a second biopsy. The C-statistic was 0.650 (95% CI 0.632, 0.668) for the first biopsy and 0.664 (95% CI 0.607, 0.721) for the second biopsy. The C-statistic for the second biopsy was statistically significantly greater than 0.5 (p <0.001) and overlapped with that from the first biopsy.",
            "output": [
                "Is the performance of prostate specific antigen for predicting prostate cancer maintained after a prior negative prostate biopsy?"
            ]
        },
        {
            "id": "task847-1cc7f790e8954a3fa4f4c1360eab0068",
            "input": "We examined hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and nuclear factor-kappaB in acquired cystic disease of the kidney associated with renal cell carcinoma to elucidate the roles of these factors in cyst formation and subsequent tumor transformation.', 'Immunohistochemical expression of hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB (active form) were examined in 20 normal kidney samples obtained from nephrectomy for localized renal cell carcinoma and 25 kidneys with acquired cystic disease associated renal cell carcinoma from 23 patients on dialysis.', 'Only faint or weak immunostaining for hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB was observed in normal kidney tissues. In nontumor areas of the kidneys with acquired cystic disease expressions of these 3 proteins was up-regulated in tubular and cyst epithelial cells. Acquired cysts were classified into 3 types according to cyst epithelium morphology, namely flat, cuboidal and hyperplastic. Hyperplastic cysts were the predominant cysts expressing hypoxia-inducible protein 2 and hypoxia-inducible factor-1alpha. Although up-regulation of hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB was observed in renal cell carcinoma, positive hypoxia-inducible protein 2 immunostaining was detected predominantly in papillary renal cell carcinoma, while positive hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB immunostaining was prominent in clear cell renal cell carcinoma.",
            "output": [
                "Is over expression of hypoxia-inducible protein 2 , hypoxia-inducible factor-1alpha and nuclear factor kappaB putatively involved in acquired renal cyst formation and subsequent tumor transformation in patients with end stage renal failure?"
            ]
        },
        {
            "id": "task847-835b7a3ddae946fb9317f1bd5be28de1",
            "input": "The purpose of this study was to determine the effects of enamel matrix derivative on mRNA expression of markers related to periodontal healing.', 'Murine osteoprogenitor cells (MC3T3-E1) were grown for 12 and 16 days in mineralization media and stimulated with 100 microg/mL Emdogain (EMD). Cell cultures treated with 2% and 10% fetal calf serum (FCS) served as control. The mRNA expression of bone sialoprotein (BSP), osteopontin (OPN), and runt-related protein 2 (Runx2) was analyzed by real-time polymerase chain reaction. One-way analysis of variance was used for statistical analysis.', 'Stimulation with EMD significantly (P < .01) enhanced mRNA expression of BSP up to 13.9-fold and of OPN up to 3.2-fold at day 16 compared with the 2% FCS control. The expression of mRNA for transcription factor Runx2 was not significantly changed.",
            "output": [
                "Does stimulation of osteoblasts with Emdogain increase the expression of specific mineralization markers?"
            ]
        },
        {
            "id": "task847-3d1ba5e27b99402d91750865eb4fe205",
            "input": "Oxytocin is believed to be involved in ejaculation by increasing sperm number and contracting ejaculatory tissues. However, oxytocin may mediate these effects via oxytocin or vasopressin (AVP) receptors. The aim of this study was to determine the effect of oxytocin and AVP on peripheral tissues involved in ejaculation and to identify the receptor subtype(s) involved.', 'Standard tissue bath techniques were used to measure isometric tension from tissues involved in ejaculation and erection.', 'Oxytocin and AVP failed to elicit a tonic contractile response in rat and rabbit testes, vas deferens, epididymis, seminal vesicles and prostate. In contrast, oxytocin and AVP elicited large tonic contractions in erectile (corpus spongiosum and corpus cavernosum) and ejaculatory (prostatic urethra, bladder neck and ejaculatory duct) tissues in a concentration-dependent manner. The selective oxytocin agonist, [Thr4,Gly7]-oxytocin and the V2 agonist, [deamino-Cys1,Val4,D-Arg8]-vasopressin (dDAVP), failed to contract tissues. Oxytocin and AVP-induced contractions were weakly antagonized by the selective oxytocin antagonist, L-368899 but potently antagonized by the V1A antagonist, SR49059. The V1B antagonist SSR149415 failed to antagonize AVP contractions except in rabbit bladder neck. Neither L-368899 nor SR49059 antagonized endothelin-1-induced contractions.",
            "output": [
                "Are oxytocin-induced contractions within rat and rabbit ejaculatory tissues mediated by vasopressin V1A receptors and not oxytocin receptors?"
            ]
        },
        {
            "id": "task847-85ab1af4c8294d4581829f13227f6ce2",
            "input": "To investigate the efficiency of Agrobacterium tumefaciens mediated transformation of Aspergillus fumigatus by using pyrG as a recessive selectable marker.', 'FAP1 and SHO1 genes target sequences, composed of a selectable marker pyrG and the flanking sequences of the FAP1 and the SHO1 genes, were cloned into a binary plasmid pDHt/sk, respectively. The produced plasmids were transformed into A. tumefaciens. The A. tumefaciens and uracil auxotroph A. fumigatus were cocultured in induction medium without uricil and uridine at 24 degrees C for 48 h. To inhibit growth of A. tumefaciens and to select transformants, the cultures were transferred to 37 degrees C and incubated for another 48 h.', 'In this study, A. tumefaciens-mediated transformation of A. fumigatus produced high homologous recombination rates, which was 44% (7 of 16) for FAP1 and 35% (7 of 20) for SHO1.",
            "output": [
                "Is [ Agrobacterium tumefaciens-mediated transformation of uracil auxotroph Aspergillus fumigatus an efficient method for target gene knockout ]?"
            ]
        },
        {
            "id": "task847-8e4a6e6d95144fbb8f167490c6512919",
            "input": "Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr; OMIM 604129) is a rare manifestation of dystrophic epidermolysis bullosa (DEB), characterized by pruritus, nodular prurigo-like lesions and fragility of the skin mainly in the extremities. Fewer than 40 patients with autosomal dominant or recessive inheritance, or sporadic DEB-Pr, have been described in the literature.', 'To disclose mutations in DEB-Pr and to elucidate the role of other pathogenic factors which may influence the pruriginous phenotype.', 'Seven patients with typical clinical features of DEB-Pr were studied.', 'In all patients, mutations in the gene encoding collagen VII (COL7A1) were disclosed, two of them novel (p.G2623V, p.E2736K). Three mutations were dominant, three recessive and one de novo. In the families with dominant DEB there were one or more members with DEB-Pr, but also at least one affected sibling who did not develop DEB-Pr. In six of seven patients, the clinical history revealed factors that initially induced pruritus, such as atopy, pregnancy, thyroid hormone imbalance, diabetes, infections and contact sensitization. Common filaggrin mutations were ruled out in all patients and normal filaggrin staining was found in the skin samples.",
            "output": [
                "Is dystrophic epidermolysis bullosa pruriginosa associated with frequent FLG gene mutations?"
            ]
        },
        {
            "id": "task847-a5072acdf9c94c83a55fc959aa62e275",
            "input": "More and more experiments have shown that transcription and mRNA processing are not two independent events but are tightly coupled to each other. Both promoter and transcription rate were found to influence alternative splicing. More than half of human genes have alternative promoters, but it is still not clear why there are so many alternative promoters and what their biological roles are.', 'In this study, we explored whether there is a functional correlation between alternative promoters and alternative splicing by a genome-wide analysis of human and mouse genes. We constructed a large data set of genes with alternative promoter and alternative splicing annotations. By analyzing these genes, we showed that genes with alternative promoters tended to demonstrate alternative splicing compare to genes with single promoter, and, genes with more alternative promoters tend to have more alternative splicing variants. Furthermore, transcripts from different alternative promoters tended to splice differently.",
            "output": [
                "Do alternative promoters influence alternative splicing at the genomic level?"
            ]
        },
        {
            "id": "task847-38cb5ea269e14d53a6a171b49cc5d6fc",
            "input": "With the advancement of biomedical technology, artificial materials have been developed to replace diseased, damaged or nonfunctional body parts. Among such materials, ultra high molecular weight alkane or modified alkyl polymers have been extensively used in heart valves, stents, pacemakers, ear implants, as well as total joint replacement devices. Although much research has been undertaken to design the most non-reactive biologically inert polyethylene derivatives, strong inflammatory responses followed by rejection and failure of the implant have been noted.', 'Purification of the alkane polymers from the site of inflammation revealed extensive \"in vivo\" oxidation as detected by fourier transformed infra-red spectroscopy. Herein, we report the novel observation that oxidized alkane polymers induced activation of TLR1/2 pathway as determined by ligand dependent changes in intrinsic tyrosine fluorescence intensity and NF-kappaB luciferase gene assays. Oxidized polymers were very effective in activating dendritic cells and inducing secretion of pro-inflammatory cytokines. Molecular docking of the oxidized alkanes designated ligand specificity and polymeric conformations fitting into the TLR1/2 binding grooves.",
            "output": [
                "Is immunogenecity of modified alkane polymers mediated through TLR1/2 activation?"
            ]
        },
        {
            "id": "task847-17f74e80f1fa4ec5b71722acea19b192",
            "input": "Epigenetic dysregulation is implicated in pituitary neoplasia as the cause of silencing of several tumor suppressor genes. However, the upstream mediators of such events remain unknown.', 'We examined the three members of the DNA methyltransferase (DNMT) enzyme family in normal and neoplastic human and mouse pituitary cells.', 'This study was performed at a university-affiliated cancer research institute.', 'Gene expression, promoter DNA methylation, histone modifications, and cell proliferation were determined.', \"In contrast to DNMT1 and DNMT3a, DNMT3b was expressed at relatively higher levels in neoplastic pituitary cells. However, examination of the human DNMT3b 5' region showed uniformly low DNA methylation levels with little difference between normal and tumor samples. Through pharmacological methylation inhibition or histone deacetylation inhibition, we identified that DNMT3b gene expression is subject to histone modifications. Down-regulation of DNMT3b resulted in induction of retinoblastoma, p21, and p27, and reduction in cell proliferation. These targeted effects were associated with enhanced histone 3 acetylation and diminished histone methylation.",
            "output": [
                "Does deoxyribonucleic acid methyltransferase 3B promote epigenetic silencing through histone 3 chromatin modifications in pituitary cells?"
            ]
        },
        {
            "id": "task847-0ed0d4ba200e43f8be6a533786902889",
            "input": "Insulin resistance is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). The molecular mechanisms underlying reduced insulin-mediated glycogen synthesis in skeletal muscle of patients with PCOS have not been established.', 'We investigated protein content, activity, and phosphorylation of glycogen synthase (GS) and its major upstream inhibitor, GS kinase (GSK)-3 in skeletal muscle biopsies from 24 PCOS patients (before treatment) and 14 matched control subjects and 10 PCOS patients after 16 wk treatment with pioglitazone. All were metabolically characterized by euglycemic-hyperinsulinemic clamps and indirect calorimetry.', 'Reduced insulin-mediated glucose disposal (P < 0.05) was associated with a lower insulin-stimulated GS activity in PCOS patients (P < 0.05), compared with controls. This was, in part, explained by absent insulin-mediated dephosphorylation of GS at the NH2-terminal sites 2+2a, whereas dephosphorylation at the COOH-terminal sites 3a+3b was intact in PCOS subjects (P < 0.05). Consistently, multiple linear regression analysis showed that insulin activation of GS was dependent on dephosphorylation of sites 3a+3b in women with PCOS. No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P < 0.05) and restored the ability of insulin to dephosphorylate GS at sites 2 and 2a.",
            "output": [
                "Is impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome reversed by pioglitazone treatment?"
            ]
        },
        {
            "id": "task847-bdc9663658d94a8986a951ca282d7e36",
            "input": "BRCA1- and BRCA2-associated tumors appear to have distinct molecular signatures. BRCA1-associated tumors are predominantly basal-like cancers, whereas BRCA2-associated tumors have a predominant luminal-like phenotype. These two molecular signatures reflect in part the two cell types found in the terminal duct lobular unit of the breast. To elucidate novel genes involved in these two spectra of breast tumorigenesis we performed global gene expression analysis on breast tumors from germline BRCA1 and BRCA2 mutation carriers.', 'Breast tumor RNAs from 7 BRCA1 and 6 BRCA2 mutation carriers were profiled using UHN human 19K cDNA microarrays. Supervised univariate analyses were conducted to identify genes differentially expressed between BRCA1 and BRCA2-associated tumors. Selected discriminatory genes were validated using real time reverse transcription polymerase chain reaction in the tumor RNAs, and/or by immunohistochemistry (IHC) or by in situ hybridization (ISH) on tissue microarrays (TMAs) containing an independent set of 58 BRCA1 and 64 BRCA2-associated tumors.', 'Genes more highly expressed in BRCA1-associated tumors included stathmin, osteopontin, TGFbeta2 and Jagged 1 in addition to genes previously identified as characteristic of basal-like breast cancers. BRCA2-associated cancers were characterized by the higher relative expression of FGF1 and FGFR2. FGFR2 protein was also more highly expressed in BRCA2-associated cancers (P = 0.004).",
            "output": [
                "Does expression profiling of familial breast cancers demonstrate higher expression of FGFR2 in BRCA2-associated tumors?"
            ]
        },
        {
            "id": "task847-26b6688f02304e069f77993fd17a8bef",
            "input": "We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The downstream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY administration modulates the suppressive action of insulin on EGP via hepatic sympathetic or parasympathetic innervation.', 'The effects of a continuous intracerebroventricular infusion of NPY on glucose turnover were determined in rats during a hyperinsulinemic-euglycemic clamp. Either rats were sham operated, or the liver was sympathetically (hepatic sympathectomy) or parasympathetically (hepatic parasympathectomy) denervated.', 'Sympathectomy or parasympathectomy did not affect the capacity of insulin to suppress EGP in intracerebroventricular vehicle-infused animals (50 +/- 8 vs. 49 +/- 6 vs. 55 +/- 6%, in hepatic sympathectomy vs. hepatic parasympathectomy vs. sham, respectively). Intracerebroventricular infusion of NPY significantly hampered the suppression of EGP by insulin in sham-denervated animals (29 +/- 9 vs. 55 +/- 6% for NPY/sham vs. vehicle/sham, respectively, P = 0.038). Selective sympathetic denervation of the liver completely blocked the effect of intracerebroventricular NPY administration on insulin action to suppress EGP (NPY/hepatic sympathectomy, 57 +/- 7%), whereas selective parasympathetic denervation had no effect (NPY/hepatic parasympathectomy, 29 +/- 7%).",
            "output": [
                "Does intracerebroventricular administration of neuropeptide Y induce hepatic insulin resistance via sympathetic innervation?"
            ]
        },
        {
            "id": "task847-0173c243a5674a129adadbd825ba691b",
            "input": "Stepping response may be considered the most important postural reaction to prevent a fall because it is the inability to respond effectively to a loss of balance that ultimately determines whether a fall occurs. However, very little has been studied on the effect of exercising on step execution behavior in the elderly.', 'To explore whether older persons who exercise regularly have faster voluntary stepping times than sedentary elderly persons. Additionally, we investigated the association between step execution behavior, self-reported physical function, and balance performance.', 'Case-control study of 48 elderly adults aged 65-91 years who live independently in retirement homes. Participants were classified as 24 exercisers (reporting >2 exercise training activities/week) and 24 age- and gender-matched inactive elderly individuals (who do not exercise regularly). The Voluntary Step Execution Test was performed as a reaction time task while standing on a force platform under single-task and dual-task conditions. Step initiation phase, foot off time, foot contact time, preparatory, and swing phases were extracted from center of pressure and ground reaction force data. Self-reported function was examined using Late-Life Function and Disability Instrument; Berg Balance Test was also performed.', 'Exercisers had significantly faster voluntary step times in single-task condition (959 vs. 1,158 ms) but not during dual-task condition (1,170 vs. 1,303 ms). Exercisers had a significantly higher Berg Balance Test (53.7 +/-3.6 vs. 49.8 +/-5.3), consumed less medication (3.3 +/-2.3 vs. 5.6 +/-2.9), and their lower extremity function scores were higher (88.61 +/-2.3 vs. 73.1 +/-2.7) than those of inactive subjects.",
            "output": [
                "Is regular exercise in the elderly effective to preserve the speed of voluntary stepping under single-task condition but not under dual-task condition . A case-control study?"
            ]
        },
        {
            "id": "task847-35b66e347809463585101a37fcd465f3",
            "input": "Expression of osteopontin correlates with tumor progression and metastasis. The mechanisms by which osteopontin promotes tumor cell survival remain unclear. Here we used short-hairpin RNA-mediated gene silencing to investigate the antitumor effects by osteopontin depletion in hepatocellular carcinoma (HCC).', 'We applied polyethylenimine nanoparticles to deliver a short-hairpin RNA for depletion of osteopontin expression in HCC cells. Tumorigenicity and metastatic potentials of HCC cells were studied in vitro and in nude mice. Nuclear factor-kappaB (NF-kappaB) activation was analyzed by gel shift assay and luciferase analysis. The expressions of integrins were examined by real-time reverse-transcription polymerase chain reaction. Apoptosis was examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and mitochondrial membrane potential analysis.', 'Down-regulation of osteopontin inhibited HCC cell growth, anchorage-independent growth, adhesion with fibronectin and invasion through extracellular matrix in vitro, and suppressed tumorigenicity and lung metastasis in nude mice. Osteopontin silencing resulted in suppression of alphav, beta1, and beta3 integrin expressions, blockade of NF-kappaB activation, inhibition of Bcl-2/Bcl-xL and XIAP expressions, increase of Bax expression, and induction of a mitochondria-mediated apoptosis. Furthermore, down-regulation of osteopontin inhibited drug-induced NF-kappaB activation and sensitized HCC cells to chemotherapeutic agents in vitro, which led to complete regression of HCC xenografts in nude mice.",
            "output": [
                "Does down-regulation of osteopontin suppress growth and metastasis of hepatocellular carcinoma via induction of apoptosis?"
            ]
        },
        {
            "id": "task847-3549734623ea4beeb43f82c7f18f4a3c",
            "input": "Despite adequate epidural analgesia, up to 97% of patients undergoing thoracotomy experience ipsilateral shoulder pain. In this setting, this study evaluated the safety and the efficacy of pre-emptive gabapentin.', 'A double-blind, placebo-controlled study was undertaken in 51 patients randomized into two groups. Two hours before surgery, 23 patients received gabapentin 1200 mg po (Group G), and 28 patients received placebo (Group P). Shoulder pain and postoperative pain, at the surgical site, were monitored every four hours for 24 hr, using a numerical rating scale. Subcutaneous hydromorphone was administered for rescue analgesia against shoulder pain.', 'Forty-four patients complained of shoulder pain (prevalence of 86%). Demographic and surgical data were similar between the two groups. There were no significant differences in the total cumulative doses of hydromorphone administered at eight, 16, and 24 hr, nor were there differences in individual numerical rating scale scores for shoulder pain. The groups were similar with respect to the degree of pain at the surgical site. The frequency of side effects between groups at corresponding time intervals was also similar, with the exception of sedation. At four hours, the incidence of sedation scores > 1 was greater in Group G (21/23 patients), compared to Group P (18/28 patients; P = 0.025). In contrast, by 24 hr, 5/18 patients in Group P had sedation scores > 1, compared to 0/28 patients in Group G (P = 0.05).",
            "output": [
                "Does gabapentin reduce post-thoracotomy shoulder pain : a randomized , double-blind placebo-controlled study?"
            ]
        },
        {
            "id": "task847-37fd5da902214ea9a0cbd0d76d8173a1",
            "input": "Pulmonary dysfunction commonly occurs following coronary artery bypass graft (CABG) surgery, increasing morbidity and mortality. We hypothesized that thoracic epidural anesthesia (TEA) would improve pulmonary function and would decrease complications in patients undergoing CABG surgery.', 'This prospective, randomized, controlled trial was conducted with Ethics Board approval. Fifty patients, undergoing CABG surgery, were randomized to the epidural group or to the patient-controlled analgesia morphine group. Patients in the epidural group received a high, thoracic epidural, preoperatively. Intraoperatively, 0.75% ropivacaine was infused, followed postoperatively, by 0.2% ropivacaine for 48 hr. Outcome measurements included: visual analogue pain scores; spirometry; atelectasis scores on chest radiographs; and the incidence of atrial fibrillation.', 'Twenty-five patients were enrolled in each group. Patients in the epidural group had significantly less pain on the operative day, and for the subsequent two days. Compared to baseline, the forced expiratory volume in one second was significantly higher in the epidural group, on the first and second postoperative days (43.7 +/- 12.2% vs 36.4 +/- 12.0%, p < 0.002, and 43.3 +/- 12.5% vs 38.4 +/- 11.0%, p <0.05). There was significantly more atelectasis in the control group, four hours postoperatively (p < 0.04); however, on the third, postoperative day, the groups were similar with regards to this outcome. The incidence of atrial fibrillation was similar in both groups, and there were no complications related to the epidural.",
            "output": [
                "Does thoracic epidural analgesia improve pulmonary function in patients undergoing cardiac surgery?"
            ]
        },
        {
            "id": "task847-f3d13c53345341f5b06e5da92448c091",
            "input": "The relative effects of obesity compared to alcohol on liver injury are uncertain. We examined their effects on alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) levels in a population-based cohort.', 'Adult residents (2610: 1326 males, 1284 females) from Busselton, Australia, participated in a cross-sectional survey determining alcohol intake as determined by a validated questionnaire, anthropometric measurements and serum analysis. Alcohol consumption was classified as never, light (<140 g/week), moderate (140-420 g/week) or heavy (>420 g/week).', 'The majority of subjects were either overweight (41%) or obese (17%). A minority of subjects were moderate (25%) or heavy drinkers (4%). Body mass index (BMI) and waist circumference were strongly associated with ALT and GGT (P < 0.0001 for all tests). Alcohol consumption was modestly associated with ALT in females (P = 0.01) but not in males (P = 0.9). In contrast, GGT was significantly associated with alcohol in both genders (P < 0.0005). The risk of an elevated ALT was seven-fold higher with obesity but only two-fold higher with moderate or heavy alcohol use. Obesity accounted for half of all elevated ALT levels in the cohort, whereas alcohol excess was responsible for less than 10%. No synergistic effect was observed between BMI or waist circumference and alcohol on ALT or GGT (P > 0.2 for all tests).",
            "output": [
                "Is body mass index a stronger predictor of alanine aminotransaminase levels than alcohol consumption?"
            ]
        },
        {
            "id": "task847-d08ef3c035ba4d85ba06cee44924e073",
            "input": "The aim of this study was to investigate whether mRNA expression of the apoptosis-associated genes, XAF1 and XIAP, in bladder cancer patients correlates with response to neoadjuvant treatment.', 'Gene expression was analyzed by a real-time quantitative PCR method in paired samples from 14 bladder cancer patients treated with a combination of neoadjuvant gemcitabine and cisplatin. The prognostic significance of XAF1 and XIAP mRNA expression as well as the correlation with several clinical and pathological findings were evaluated.', 'The clinical response in the XAF1-high subset (n = 5) was remarkably higher compared with the XAF1-low subset (n = 9) (100% vs. 44.4%; P = 0.038). These results translated into a notably improvement of progression-free survival (PFS) in the XAF1-high subset (log-rank P = 0.012). In addition, patients in the XAF1-high subset had a 3.9-fold decreased chance of dying from the disease (hazard ratio for death (HR), 0.257; (CI 95%), 0.043-1.536, P = 0.036). When we evaluated the expression of XIAP, although an inverse correlation was found between expression and pathological response, there were no statistically significant associations with the clinical response, the length of PFS, and OS.",
            "output": [
                "Does xAF1 mRNA expression improve progression-free and overall survival for patients with advanced bladder cancer treated with neoadjuvant chemotherapy?"
            ]
        },
        {
            "id": "task847-7358a64d5b1844fd9427b6d3bf6cfafc",
            "input": "For many years, adipose tissue has been mainly considered as an inert reservoir for storing triglycerides. Since the discovery that adipocytes may secrete a variety of bioactive molecules (hormones, chemokines, and cytokines), an endocrine and paracrine role for white adipose tissue (WAT) in the regulation of energy balance and other physiological processes has been established, particularly with regard to brain and muscle. In contrast, little is known about the interactions of WAT with liver. Hence, we examined the effect of the secretory products of WAT on hepatocytes. Conditioned medium of human WAT explants induced significant steatosis in hepatocyte cell lines. Factor(s) responsible for the conditioned medium-induced steatosis were screened by a battery of blocking antibodies against different cytokines/chemokines shown to be secreted by WAT. In contrast to interleukin-8 and interleukin-6, the monocyte chemoattractant protein-1 was capable of inducing steatosis in hepatocytes in a time-dependent manner at concentrations similar to those found in conditioned medium. Incubation of conditioned medium with antimonocyte chemoattractant protein-1 antibodies prevented triglyceride accumulation. Investigation of the mechanism leading to the triglyceride accumulation showed that both a diminution of apolipoprotein B secretion and an increase in phosphoenolpyruvate carboxykinase messenger RNA may be involved.",
            "output": [
                "Does monocyte chemoattractant protein-1 secreted by adipose tissue induce direct lipid accumulation in hepatocytes?"
            ]
        },
        {
            "id": "task847-cd1bfd627c8548a38f83f597f550bace",
            "input": "Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate the role of this homeodomain DNA-binding protein in T cell development, we generated transgenic mice expressing the N-terminal fragment of Pbx1 (Pbx1NT) under the control of the Lck proximal promoter.', 'Pbx1NT causes Prep1 cytosolic sequestration, abolishes Prep1-dependent DNA-binding activity and results in reduced Pbx2 expression in developing thymocytes. Transgenic thymi reveal increased numbers of CD4(-) CD8(-) CD44(-) (DN3 and DN4) thymocytes, due to a higher frequency of DN2 and DN4 Pbx1NT thymocytes in the S phase. Transgenic thymocytes however do not accumulate at later stages, as revealed by a normal representation of CD4/CD8 double positive and single positive thymocytes, due to a higher rate of apoptotic cell death of DN4 Pbx1NT thymocytes.",
            "output": [
                "Does cytosolic sequestration of Prep1 influence early stages of T cell development?"
            ]
        },
        {
            "id": "task847-af1580be418a42d384cc0c9330aecd23",
            "input": "Benefits of adopting restrictive guidelines for erythrocyte transfusions are still controversial. The objective of this study was to verify if a very strict guideline could reduce erythrocyte transfusions in preterm infants without adverse outcomes.', 'Two prospective cohorts of neonates with gestational age < 37 weeks and birth weight < 1500 g were studied. Neonates born in Period 1 were submitted to a strict guideline for erythrocyte transfusions. In Period 2, a new stricter protocol was introduced. Infants of both periods were compared regarding number of transfusions and clinical outcome.', 'The median number of transfusions decreased from 2 (1 to 14) in Period 1 to 1 (1-9), P = 0.001, in Period 2. The linear regression multivariate analysis showed that the implementation of the stricter guideline was associated with a reduction in the number of transfusions received by patients by 0.55 (95% confidence interval: -0.08; -1.02) units/patients. Number of apnea episodes, weight at 28 days of life and days of hospital stay were similar in both periods. Intra-hospital death was lower in Period 2.",
            "output": [
                "Does a very strict guideline reduce the number of erythrocyte transfusions in preterm infants?"
            ]
        },
        {
            "id": "task847-3619e6b4af564173bfeee26e743879bc",
            "input": "The overall incidence of male breast cancer is around 1% of all breast cancers and is on the rise. In this review we aim to present various aspects of male breast cancer with particular emphasis on incidence, risk factors, patho-physiology, treatment, prognostic factors, and outcome.', 'Information on all aspects of male breast cancer was gathered from available relevant literature on male breast cancer from the MEDLINE database over the past 32 years from 1975 to 2007. Various reported studies were scrutinized for emerging evidence. Incidence data were also obtained from the IARC, Cancer Mondial database.",
            "output": [
                "Is male breast cancer : the scenario changing?"
            ]
        },
        {
            "id": "task847-372ec79cefee49a5af629cee89d4a6f8",
            "input": "Physiological data suggest that autumn leaf colours of deciduous trees are adaptations to environmental stress. Recently, the evolution of autumn colouration has been linked to tree condition and defence. Most current hypotheses presume that autumn colours vary between tree individuals. This study was designed to test if within-tree variation should be taken into account in experimental and theoretical research on autumn colouration.', 'Distribution of red autumn leaf colours was compared between partially dead and vigorous specimens of Norway maple (Acer platanoides) in a 3-year study. In August, the amount of reddish foliage was estimated in pairs of partially dead and control trees. Within-tree variation in the distribution of reddish leaves was evaluated. Leaf nitrogen and carbon concentrations were analysed.', 'Reddish leaf colours were more frequent in partially dead trees than in control trees. Reddish leaves were evenly distributed in control trees, while patchiness of red leaf pigments was pronounced in partially dead trees. Large patches of red leaves were found beneath or next to dead tree parts. These patches reoccurred every year. Leaf nitrogen concentration was lower in reddish than in green leaves but the phenomenon seemed similar in both partially dead and control trees.",
            "output": [
                "Does red reveal branch die-back in Norway maple Acer platanoides?"
            ]
        },
        {
            "id": "task847-f252285623494a6d9c37a048a1b576c9",
            "input": "The earliest response of esophageal mucosa to gastric reflux is the development of oxidative damage and inflammation. These processes contribute to the development of metaplasia known as Barrett's esophagus, as well as the progression to malignancy. Secretory phospholipase A(2) is a mediator of inflammation with levels that are increased in Barrett's metaplasia and carcinoma when compared with levels in normal samples. Our goal is to determine the role of secretory phospholipase A(2) in the development of reflux-associated changes in the esophageal mucosa.\", 'Secretory phospholipase A(2)-deficient mice (C57BL/6, n = 5) and mice known to express high levels of secretory phospholipase A(2) (BALB/c, n = 5) underwent side-to-side surgical anastomosis of the first portion of the duodenum and gastroesophageal junction, allowing exposure of esophageal mucosa to duodenal and gastric contents duodeno-gastroesophageal anastomosis. Control animals (n = 5) of each strain underwent laparotomy with esophagotomy and repair. Tissue was frozen in embedding medium. Hematoxylin and eosin staining and Ki67 and secretory phospholipase A(2) immunohistochemistry were used to evaluate esophageal tissue and its response to duodeno-gastroesophageal anastomosis.', 'Immunofluorescent staining confirmed the absence of secretory phospholipase A(2) in C57BL/6 mice and its presence in BALB/c mice. Hematoxylin and eosin staining demonstrated significant thickening of the esophageal mucosa in response to gastroesophageal reflux in the presence of secretory phospholipase A(2). Mice known to express high levels of secretory phospholipase A(2) also demonstrated increased numbers of proliferating cells. Secretory phospholipase A(2)-deficient mice were immune to the early changes induced by mixed reflux.",
            "output": [
                "Is secretory phospholipase A2 required to produce histologic changes associated with gastroduodenal reflux in a murine model?"
            ]
        },
        {
            "id": "task847-656be898b2734f44adbe4582a792d281",
            "input": "The hepatitis B virus X protein (HBx) plays critical roles in cell survival via modulation of signaling pathways. In our previous studies, we reported that HBx inhibited the growth of CCL13-HBx-stable cells (Chang-HBx cells) in vitro and tumor formation in vivo in CCL13-HBx-cell-injected nude mice; however, this inhibition mechanism is unclear.', 'To investigate the role of HBx in Wnt-3/beta-catenin signaling pathways, we focused on the key molecules GSK-3beta and beta-catenin, and analyzed by Western blotting and immunofluorescence staining.', 'Results indicated that following HBx induction, GSK-3beta activity was up-regulated, the expression and accumulation of beta-catenin in the nucleus were decreased, and cell proliferation was suppressed. Inhibition of GSK-3beta activity by pharmacological inhibitors rescued the expression and accumulation of beta-catenin in the nucleus and facilitated cell proliferation and growth following HBx induction. The localization of beta-catenin, which is involved in cell proliferation, and mediated by GSK-3beta activation was also demonstrated.",
            "output": [
                "Does hBx inhibit the growth of CCL13-HBX-stable cells via the GSK-3beta/beta-catenin cascade?"
            ]
        },
        {
            "id": "task847-d23fb4169862459593f97433dbddd7a4",
            "input": "Although serum amyloid A (SAA) is an established biomarker of coronary artery disease (CAD), its direct role in matrix degradation is obscure. This study investigated the effect of SAA on the expression of matrix metalloproteinase-10 (MMP-10) in endothelial cells. The effect of celecoxib on SAA-dependent MMP-10 expression and its possible mediator were also investigated.', 'From our time course microarray screening, SAA (20 microg/ml) was found to increase MMP-10 mRNA expression over time (4-48 h) in human endothelial cells. Quantitative real-time PCR confirmed this transcriptional induction. Correspondingly, secreted MMP-10 protein was also markedly induced by SAA treatment for 24 h in a dose-dependent manner. We further examined cyclooxygenase-2 (COX-2) and its major product, prostaglandin E(2) (PGE(2)), as possible mediators of MMP-10 induction. Direct PGE(2) treatment could result in MMP-10 induction. Celecoxib, a selective COX-2 inhibitor, suppressed MMP-10 secretion induced by SAA.",
            "output": [
                "Does celecoxib inhibit serum amyloid a-induced matrix metalloproteinase-10 expression in human endothelial cells?"
            ]
        },
        {
            "id": "task847-b1421baa28144bd2af783c9d1709c125",
            "input": "The decrease in glomerular filtration rate (GFR), which is characteristic of obstructive uropathy, was suggested to be associated with attenuated nitric oxide (NO) generation. Since availability of L-arginine, the sole precursor for NO, governs NO synthesis, we aimed to determine the role of glomerular arginine transport in rats subjected to 24 h of bilateral ureteral ligation (BUO).', 'Glomerular arginine transport was measured by uptake of radiolabeled arginine ([(3)H]-L-arginine), cationic amino acid transporters (CAT)-1 and -2 and arginases I and II mRNA expression were determined using reverse transcription-polymerase chain reaction. CAT-1, arginase I, and arginase II protein contents were evaluated by Western blotting.', 'L-Arginine transport by freshly harvested glomeruli from BUO rats was significantly augmented than in controls. The aforementioned findings were associated with a significant increase in glomerular CAT-1 mRNA expression, while CAT-2 mRNA was unchanged. Western blotting demonstrated a significant increase in CAT-1 abundance in BUO. Expression of both glomerular arginase I and II mRNA and protein content were significantly elevated in BUO.",
            "output": [
                "Is arginine transport augmented , through modulation of cationic amino acid transporter-1 , in obstructive uropathy in rats?"
            ]
        },
        {
            "id": "task847-c9a6dda301104b4b9f09d42008bb2dc1",
            "input": "Mesangial activation occurs in many forms of renal disease that progress to renal failure. Mitogen-activated protein kinases (MAPKs) are important mediators involved in the intracellular network of interacting proteins that transduce extracellular stimuli to intracellular responses. The extracellular signal-regulated kinases 5 (Erk5) MAPK pathway has been involved in regulating several cellular responses. Thus, we examined the expression of Erk5 in human renal tissue and the function of Erk5 in cultured human mesangial cells.', 'Erk5 was visualized in human renal tissue by immunohistochemistry and in mesangial cells by immunofluorescence microscopy using the anti-Erk5 C-terminus antibody. Erk5 expression and activation, and collagen I expression were determined by western blot. To generate a dominant-negative form of the Erk5 in human mesangial cells, an EcoRI fragment from wild-type pCEFL-HA-Erk5 was subcloned into the EcoRI site of pCDNA3. Cell proliferation was analysed by an MTT-based assay. Cell contraction was analysed by studying the changes in the planar cell surface area.', 'Erk5 was expressed in the kidney, mainly localized at the glomerular mesangium. In cultured human mesangial cells, Erk5 was activated by foetal calf serum (FCS), high glucose, endothelin-1, platelet-activating factor (PAF), epidermal growth factor (EGF) and transforming growth factor beta-1 (TGF-beta1). The expression of a dominant-negative form of Erk5 in human mesangial cells resulted in a significant decrease in proliferation, EGF-induced cell contraction and TGF-beta1-induced collagen I expression.",
            "output": [
                "Does the mitogen-activated protein kinase Erk5 mediate human mesangial cell activation?"
            ]
        },
        {
            "id": "task847-ff58fef93a4b43948103d20dc17e170e",
            "input": "No polymorphisms affecting serum FSH levels have been described in the human FSHB gene. We have identified a potential regulatory single nucleotide polymorphism (SNP, rs10835638; G/T) 211 bp upstream from the FSHB mRNA transcription start-site, located within a highly conserved region among placental mammals. We aimed to determine the correlation of carrier status of rs10835638 alternative alleles with serum FSH level in men, and testicular and hormonal parameters.', 'A quantitative genetic association study using a cohort of healthy men (n = 554; age 19.2 +/- 1.7 years) visiting the Centre of Andrology, Tartu University Hospital, Estonia.', 'Rs10835638 (allele frequencies: G 87.6%, T 12.4%) was significantly associated with serum FSH level (analysis of variance: F = 13.0, P = 0.0016, df = 1; regression testing for a linear trend: P = 0.0003). Subjects with the GG genotype exhibited higher FSH levels (3.37 +/- 1.79 IU/l, n = 423) compared with heterozygotes (2.84 +/- 1.54 IU/l, n = 125) (P = 0.0005), the group of T-allele carriers (GT+TT, 2.78 +/- 1.51 IU/l, n = 131) (P = 0.0005) and TT-homozygotes (2.02 +/- 0.81 IU/L, n = 6) (P = 0.031). Rs10835638 was also associated with significant (P < 0.05) reduction in free testosterone index and testes volume, but increased semen volume, sex hormone-binding globulin, serum testosterone and estradiol. LH and inhibin-B levels did not differ significantly between groups.",
            "output": [
                "Is fSHB promoter polymorphism within evolutionary conserved element associated with serum FSH level in men?"
            ]
        },
        {
            "id": "task847-4afe8d7f6e954d448c0e4143291889e2",
            "input": "It is well established that African Americans (AA) experience greater pain associated with a variety of clinical conditions, and greater pain sensitivity to experimental pain tasks relative to non-Hispanic Whites (W). Notably, African Americans do not show the same relationships involving endogenous pain regulatory mechanisms and pain sensitivity documented in Caucasians, including positive associations between blood pressure, norepinephrine, cortisol and greater pain tolerance.', 'The purpose of this study was to examine the relationship between plasma oxytocin (OT) and pain sensitivity and to explore the relation of OT to other factors known to influence pain perception.', 'OT concentration and sensitivity to ischemic, cold pressor, and thermal pain tasks were assessed in African American (n=25) and non-Hispanic White (n=23) pre-menopausal women.', 'African American women demonstrated significantly lower pain tolerance across tasks compared with Whites (F(1,46)=6.31, p=0.0156) and also exhibited lower plasma OT levels (AA: 3.90, W: 7.05 pg/mL; p=0.0014). Greater OT levels were correlated with greater tolerance to ischemic pain (r=0.36, p=0.013) and accounted for a marginally significant portion of the ethnic difference in ischemic pain tolerance (B=+0.29, p=0.06). Greater OT was also correlated with greater tolerance of cold pressor pain (r=0.31, p=0.03); however, this association was no longer seen after the variance due to ethnicity was accounted for.",
            "output": [
                "Is ethnicity associated with alterations in oxytocin relationships to pain sensitivity in women?"
            ]
        },
        {
            "id": "task847-dc9482abc8c54e5cac0ee9eea378bfb5",
            "input": "In recent years, with the introduction of Enhanced Recovery After Surgery (ERAS) or Fast-Track protocols, perioperative care for colonic surgery has changed significantly. This is the experience of a single surgeon within a public hospital in New Zealand.', 'Between October 2005 and July 2007, consecutive patients undergoing segmental colonic resection by the senior author (AGH) were managed within a multimodal structured perioperative care pathway.', 'Thirty-two consecutive patients had elective colonic surgery without a stoma. Two were excluded because of cognitive impairment. The 30 remaining patients had a median age of 68.5 years (range 37-92) and a median daystay of 3 days (range 3-21). There were four (13%) readmissions, including one anastomotic leak.",
            "output": [
                "Is fast-track open colectomy possible in a New Zealand public hospital?"
            ]
        },
        {
            "id": "task847-5bdd07434ace4e5f9162cc2cfaf11f84",
            "input": "Thoracic and thoracoabdominal aortic surgery is sometimes complicated by subacute or delayed paraplegia. Pro-inflammatory cytokine interleukin-1 (IL-1) beta has been implicated in extensive inflammation and progressive neurodegeneration after ischemia. Using a rabbit model, we investigated the neuroprotective effects of IL-1 receptor antagonist (IL-1ra) in a temporal fashion.', 'Spinal cord ischemia was induced by aortic cross-clamping in New Zealand White rabbits. The animals were assigned to three groups. Group C (n = 20) received saline (0.2-mL) and Group I (n = 20) received IL-1ra (200-microg/0.2-mL) intrathecally just after reperfusion. Group S (n = 3) underwent sham operation without aortic occlusion. We assessed the neuroprotective effects of IL-1ra by evaluating neurological function, histopathological changes, and in-situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL staining). We also measured the levels of Nitric Oxide (NO) and S100beta in cerebrospinal fluid (CSF). Each evaluation was performed sequentially within 120 hours after reperfusion.', 'Group C showed progressive deterioration of motor function which became statistically significant from 48 hours after the onset of reperfusion (P < .05, P < .01, P < .001, P < .001 at 48, 72, 96, and 120 hours, respectively). Compared to Group C, a higher number of viable neurons was observed with less severe spinal cord injury in Group I (P < .01, .05 and .05 at 24, 72, and 120 hours, respectively). TUNEL-positive neurons were also significantly reduced by the administration of IL-1ra (P <.01 and .05 at 24, and 120 hours, respectively). The difference between Group C and Group I with regard to NO was significant at 72 and 120 hours (P < .05), while that in terms of S100beta was significant only at 24 hours (P < .05).",
            "output": [
                "Does interleukin-1 receptor antagonist attenuate the severity of spinal cord ischemic injury in rabbits?"
            ]
        },
        {
            "id": "task847-326b6dfe51c44f7595212c8fb2c46411",
            "input": "Classic studies of limb ischemia-reperfusion injury have been performed using young healthy mice. However, patients with peripheral vascular disease are older and often exhibit metabolic derangements that may delay healing after revascularization. Mice with genetic deletion of apolipoprotein E (ApoE(-/-)) have been used as a model in various experimental scenarios of hypercholesterolemia. These experiments evaluated the inflammatory response and changes in skeletal muscle morphology during the acute and chronic phases of limb ischemia-reperfusion injury in aged ApoE(-/-) mice.', \"Age-matched ApoE(-/-) and wild-type (Wt) mice underwent 1.5 hours of unilateral hind limb ischemia, followed by 1, 7, or 14 days of reperfusion (DR). Histologic analysis of skeletal muscle fiber injury was assessed at 1DR. Morphologic evidence of muscular fiber maturation was assessed at 14DR. Levels of MyoD and myogenin, markers of skeletal muscle differentiation, were assessed at 7 and 14DR using Western blots. Markers of inflammation, including myeloperoxidase, macrophage inflammatory protein-2 (MIP-2), monocyte chemotactic protein-1 (MCP-1), and osteopontin, were assayed using enzyme-linked immunosorbent assay and chemokine (C-C motif) receptor 2 (CCR2) using Western blots at 1, 7, and 14DR. After 1DR, tissue adenosine 5'-triphosphate (ATP) levels were measured to assess metabolic activity. Unpaired t test and Mann-Whitney test were used for comparisons.\", 'Histologic evaluation of skeletal muscle after 1DR showed no difference in the degree of injury between Wt and ApoE(-/-) mice. However, at 14DR, ApoE(-/-) mice had higher percentage of immature muscle fibers than Wt mice. Myogenin level was lower in the ApoE(-/-) mice at 7DR. Injured skeletal muscle of ApoE(-/-) mice had lower levels of myeloperoxidase than Wt mice at 7 DR and higher levels of MCP-1 at 14DR. There was no difference in the levels of tissue ATP, MIP-2, osteopontin, or CCR2 at all experimental intervals.",
            "output": [
                "Do apolipoprotein E-/- mice have delayed skeletal muscle healing after hind limb ischemia-reperfusion?"
            ]
        },
        {
            "id": "task847-75c5458452614e7482aee760fd118711",
            "input": "The efficacy of programmes to reduce long-term benzodiazepine use could be compromised by subsequent increases in contacts with the family practice. In this study the hypothesis was tested as to whether participation in a benzodiazepine discontinuation programme affects the frequency of contacts with the family practice.', 'A controlled stepped-care intervention programme to decrease long-term benzodiazepine use.', 'Family practices in the Netherlands. Subjects. The experimental group consisted of 996 long-term benzodiazepine users and a control group of 883 long-term benzodiazepine users.', 'Practice contacts before and up to 12 months after the start of the programme.', 'There was a general tendency visible for contacts to decrease during the follow-up time. The course of the number of contacts during the follow-up was not different for the experimental and control groups (p=0.45). The level of non-benzodiazepine prescriptions was generally not altered. The number of non-benzodiazepine prescriptions decreased in benzodiazepine quitters during the follow-up of the programme.",
            "output": [
                "Does a benzodiazepine discontinuation programme increase the frequency of contacts with the family practice?"
            ]
        },
        {
            "id": "task847-4cb6f9fbd2464bd6a41bdecfe3c7d6d1",
            "input": "To evaluate the role of toll-like receptors (TLR) 2 and 4 in host responses to Aspergillus fumigatus by use of cultured telomerase-immortalized human corneal epithelial cells (HCECs).', 'HCECs were stimulated with inactive antigens from A. fumigatus. The expression of TLR2 and TLR4, phosphorylation of Ikappa B-alpha (pIkappa B-alpha), and release of interleukin (IL)-1beta and IL-6 was measured with and without inhibitors to TLR2 and TLR4.', 'Exposure of HCECs to A. fumigatus antigens resulted in up-regulation of TLR2 and TLR4, activation of pIkappa B, and release of IL-1beta and IL-6 in HCECs, effects that could be inhibited by treatment with TLR2 and TLR4 antibodies.",
            "output": [
                "Do aspergillus fumigatus antigens activate immortalized human corneal epithelial cells via toll-like receptors 2 and 4?"
            ]
        },
        {
            "id": "task847-7d5daf06160e43f1bfd497cb66e99262",
            "input": "To determine the role of herpes simplex virus-1 (HSV-1) glycoprotein K(gK) in corneal infection, neuroinvasion, and virus latency in trigeminal ganglia of mice.', 'The recombinant virus HSV-1 (McKrae) Delta gK (MKDelta gK) carrying a deletion of the gK gene was constructed by insertional/deletion mutagenesis and replaced by a gene cassette constitutively expressing the enhanced green fluorescence protein. The gK deletion of the MKDelta gK virus was rescued to produce the wild-type-like virus MKgK. Balb/c mice were infected ocularly with either virus, and the infection pattern in the eye, clinical disease progression, and establishment of viral latency was monitored.', 'Mice infected with the MKDelta gK strain produced in a gK complementing cell line did not exhibit clinical signs when compared with mice infected with the MKgK virus. Direct visualization of infected eyes revealed that the MKDelta gK virus was unable to spread in mouse corneas, while the MKgK rescued virus spread efficiently. Nineteen of 20 scarified and 5/12 unscarified mice infected with the MKgK virus produced infectious virus after coculture with permissive cells, while 0/20 scarified and 0/12 unscarified mice infected with the MKDelta gK virus produced infectious virus. HSV DNA was detected in trigeminal ganglia by PCR in 19/20 scarified and 9/12 unscarified mice inoculated with MKgK, while HSV DNA was detected in the trigeminal ganglia of 3/20 scarified and 0/12 unscarified mice inoculated with MKDelta gK.",
            "output": [
                "Is the herpes simplex virus type 1 ( HSV-1 ) glycoprotein K ( gK ) essential for viral corneal spread and neuroinvasiveness?"
            ]
        },
        {
            "id": "task847-b158deb029c9449a9e0886cd5dd1e770",
            "input": "To verify the influence of a non-steroidal anti-inflammatory drug (NSAID), ketorolac (topical and oral) on the intraocular pressure reduction induced by 0.005% latanoprost topical administration, both in patients affected by primary open-angle glaucoma and in healthy controls.', 'Two groups of subjects were enrolled for this randomized, prospective, masked clinical study: 16 glaucomatous patients well controlled with 0.005% latanoprost eyedrops (group I) and 16 healthy adult volunteers (group II). Group I subjects were treated at one-week intervals with 10 mg of oral ketorolac, oral placebo, topical ketorolac, and topical placebo, respectively; for each administration modality, the switch between drug and placebo was performed in a randomized, crossover, double-blind fashion. Group II subjects followed the same protocol, with the topical once-daily 0.005% latanoprost treatment starting three days prior to the ketorolac/placebo administration. Intraocular pressure (IOP) was investigated in both groups on the day of oral/topical administration of ketorolac or placebo at baseline (8:00 AM) and at the following intervals: 1, 2, 4, 8, 12, and 24 hours.', 'No significant IOP changes after oral and topical placebo administration were observed in either group. In contrast, when the subjects received ketorolac (either oral or topical), a marked decrease in IOP was recorded, with a noticeable fall at the first hour after the NSAID administration (p = 0.01), which remained still significant 8 hours later (p < 0.05).",
            "output": [
                "Does topical and oral ketorolac administration increase the intraocular pressure-lowering effect of latanoprost?"
            ]
        },
        {
            "id": "task847-a52ef175599a42dd844eae6900e963e4",
            "input": "99mTc-HMPAO is a well-established isotope useful in the detection of regional cerebral blood flow. Diabetes gives rise to arterial atherosclerotic changes that can lead to significant end organ dysfunction, prominently affecting perfusion to the heart, kidneys, eyes and brain. In the current study, we investigated the role of 99mTc-HMPAO cerebral perfusion scans in detecting early vascular changes in the diabetic brain.', 'Cerebral perfusion studies were performed on both control and streptozotocin-(STZ) induced diabetic male Wistar rats. Rat brain imaging using a gamma camera was performed for each group 0.5, 2, 4, and 24 hours post 99mTc-HMPAO injection. Data processing for each cerebral perfusion scan was performed by drawing a region of interest (ROI) circumferentially around the brain (B). Background (BKG) due to signal from the soft tissue of each rat was subtracted. Brain 99mTc-HMPAO uptake minus background counts (net brain counts; NBC) were then compared between the two groups.', 'The NBC (mean +/- SD) for the STZ group were statistically significantly higher (p = 0.0004) than those of the control group at each of the time points studied.",
            "output": [
                "Does perfusion scanning using 99mTc-HMPAO detect early cerebrovascular changes in the diabetic rat?"
            ]
        },
        {
            "id": "task847-41867567724746d494026521836e711d",
            "input": "Allopregnanolone (ALLO) is a physiologically relevant neurosteroid modulator of GABA(A) receptors, and it exhibits a psychopharmacological profile that closely resembles the post-ingestive effects of ethanol. The 5alpha-reductase inhibitor finasteride (FIN), which inhibits biosynthesis of ALLO and structurally related neurosteroids, was previously demonstrated to reduce the maintenance of limited-access ethanol consumption. The primary aim of the current work was to determine whether FIN would reduce the acquisition of drinking in ethanol-na\u00efve mice.', 'Male C57BL/6J (B6) mice were acclimated to a reverse light/dark schedule, and were provided ad libitum access to chow and water. Following habituation to vehicle injections (VEH; 20% w/v beta-cyclodextrin; i.p.) administered 22-hour prior to drinking sessions with water only, mice were divided into 3 treatment groups: vehicle control (VEH), 50 mg/kg FIN (FIN-50), and 100 mg/kg FIN (FIN-100). Twenty-two hours after the first treatment, mice were permitted the inaugural 2-hour limited access to a 10% v/v ethanol solution (10E) and water. The acquisition of 10E consumption and underlying drinking patterns were assessed during FIN treatment (7 days) and subsequent FIN withdrawal (13 days) phases.', 'FIN dose-dependently blocked the acquisition of 10E drinking and prevented the development of ethanol preference, thereby suggesting that the GABAergic neurosteroids may be important in the establishment of stable drinking patterns. FIN-elicited reductions in 10E intake were primarily attributable to selective and marked reductions in bout frequency, as no changes were observed in bout size, duration, or lick rates following FIN treatment. FIN-treated mice continued to exhibit attenuated ethanol consumption after 2 weeks post-treatment, despite a full recovery in brain ALLO levels. A second study confirmed the rightward and downward shift in the acquisition of ethanol intake following 7 daily FIN injections. While there were no significant group differences in brain ALLO levels following the seventh day of ethanol drinking, ALLO levels were decreased by 28% in the FIN-50 group.",
            "output": [
                "Does inhibition of 5alpha-reduced steroid biosynthesis impede acquisition of ethanol drinking in male C57BL/6J mice?"
            ]
        },
        {
            "id": "task847-882b6532aebb44e3a8ac3a5b3c0dd786",
            "input": "Circadian control of behavior and physiology is a central characteristic of all living organisms. The master clock in mammals resides in the hypothalamus, where the suprachiasmatic nucleus (SCN) synchronizes daily rhythms. A variety of recent evidence indicates that the neuropeptide vasoactive intestinal peptide (VIP) is critical for normal functioning of the SCN. The aim of our study was to examine the possible role of VIP in driving circadian rhythms in the hypothalamic-pituitary-adrenal axis.', 'Circulating ACTH and corticosterone concentrations were determined by round-the-clock sampling under diurnal and circadian conditions. The responsive aspects of the hypothalamic-pituitary-adrenal axis were tested by application of acute stress by footshock and light.', 'We demonstrate that the circadian rhythms in ACTH and corticosterone are lost in VIP-deficient mice. The ability of light to induce a corticosterone response was also compromised in the mutant mice, as was photic induction of Per1 in the adrenal glands. In contrast, the acute stress response was apparently unaltered by the loss of VIP.",
            "output": [
                "Is vasoactive intestinal peptide critical for circadian regulation of glucocorticoids?"
            ]
        },
        {
            "id": "task847-0878c7ed435141b6a2536df9d4e755f3",
            "input": "ST-segment resolution (STR) is a well-established and simple tool for assessing the efficacy of reperfusion therapy in myocardial infarction. An incomplete (<50%) STR is a recognized marker of failed thrombolysis and a suitable recruitment criterion for rescue angioplasty.', 'We sought to determine the predictive value of the total absence of STR after thrombolysis in rescue angioplasty (percutaneous coronary intervention [PCI]).', 'Eighty-one consecutive patients who underwent a rescue angioplasty for failed thrombolysis in our institution from 2001 to 2007 were included. Two groups of patients were defined according to their STR extent, 90 minutes after lysis: partial resolution group 1 (10%-50% STR) vs absence of resolution group 2 (<10% STR) and compared in terms of in-hospital and long-term outcomes.', 'Patients of group 2 were more likely to experience hemodynamic deterioration (50% vs 24%; odds ratio [OR] = 3.17; P = .017), to have a Thrombolysis in Myocardial Infarction 0 flow on the culprit artery (62.3% vs 42%; OR = 2.24; P = .045), to have a multivessel disease (66.7% vs 40%; OR = 3; P = .018), and to die during index hospitalization (26.7% vs 6%; OR = 5.69; P = .013) despite statistically similar rates of PCI failure in both groups (10% vs 7%; P = .402) and similar post-PCI STR (72% +/- 18.25% vs 75% +/- 11.62%; P = .36). In multivariate analysis, total absence of STR proved to be an independent predictor of in-hospital mortality (HR = 7.02; P = .032; 95% confidence interval, 1.18-41.58). Long-term major adverse cardiac events occurred more frequently in group 2 (log rank, P = .004) and were (on the Cox regression model) independently predicted by total absence of STR (HR = 6.21; P = .023; 95% confidence interval, 1.28-29.1).",
            "output": [
                "Is total absence of ST-segment resolution after failed thrombolysis correlated with unfavorable short- and long-term outcomes despite successful rescue angioplasty?"
            ]
        },
        {
            "id": "task847-1ac742332fb04a4f8b755a4a95b15e9c",
            "input": "The objective of this study was to experimentally induce inflammatory cysts in an animal model so as to test the hypothesis that radicular cysts develop via the \"abscess pathway.\"', 'Twenty-eight perforated custom-made Teflon cages were surgically implanted into defined locations in the back of 7 Sprague Dawley rats. A week after the implantation of the cages, a known quantity of freshly grown, close allogeneic oral keratinocytes in phosphate buffer solution (PBS) was injected into each cage. One cage per animal was treated as the control that received only epithelial cells. The remaining 3 cages of each animal were trials. Seven days post epithelial cell inoculation; a suspension of 0.2 mL of Fusobacterium nucleatum (10(8) bacteria per mL) was injected into each of the 3 trial cages. Two, 12, and 24 weeks after the inoculation of the bacteria, the cages were taken out, and the tissue contents were fixed and processed by correlative light and transmission electron microscopy. Sixteen of the 21 trial cages could be processed and yielded results.', 'Inoculations of epithelial cells followed 1 week later by F. nucleatum into tissue cages resulted in the development inflammatory cysts in 2 of the 16 cages. The 2 cages contained a total of 4 cystic sites. None of the control cages showed the presence of any cyst-like pathology.",
            "output": [
                "Does experimental evidence support the abscess theory of development of radicular cysts?"
            ]
        },
        {
            "id": "task847-d9a9d3fee5e24a9ebabeb30d79684c9c",
            "input": "HMGCR(3-Hydroxy-3-methylglutaryl coenzyme A reductase), the direct target of statin inhibition, undergoes alternative splicing of exon 13, which encodes part of the statin-binding domain of the enzyme. We hypothesized that HMGCR alternative splicing might be related to the interindividual variation in plasma low-density lipoprotein cholesterol response to statin treatment.', 'We measured mRNA expression of both the full-length and the alternatively spliced HMGCR transcript lacking exon 13 (HMGCRv_1) in 170 simvastatin-incubated immortalized lymphocyte cell lines derived from participants in the Cholesterol and Pharmacogenetics (CAP) study who were treated with simvastatin 40 mg/d for 6 weeks. Greater upregulation of HMGCRv_1 in vitro was significantly correlated (P<or=0.0001) with smaller in vivo reductions of plasma total cholesterol, low-density lipoprotein cholesterol, apoprotein B, and triglycerides and explained 6% to 15% of the variation in their response to treatment. In contrast, no significant relationship was found between expression of the full-length HMGCR transcript and in vivo response. By siRNA knockdown of the full-length transcript, we found that HMGCR enzyme activity measured in cells enriched in HMGCRv_1 was relatively resistant to statin inhibition, consistent with the association of increased alternative splicing with reduced statin response in the CAP study. In addition, we found that a common HMGCR single-nucleotide polymorphism (rs3846662) located within intron 13 was associated with variation in the proportion of HMGCR mRNA that is alternatively spliced.",
            "output": [
                "Is alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase associated with plasma low-density lipoprotein cholesterol response to simvastatin?"
            ]
        },
        {
            "id": "task847-3b4c3b5cfbc14279a2e2dd8c56fa8f0f",
            "input": "Cancer immunotherapy refers to an array of strategies intended to treat progressive tumors by augmenting a patient's anti-tumor immune response. As immunotherapy is eventually incorporated into oncology treatment paradigms, it is important to understand how these therapies interact with established cancer treatments such as chemotherapy or Radiotherapy (RT). To address this, we utilized a well-established, autochthonous murine model of prostate cancer to test whether RT could augment (or diminish) the CD4 T cell response to a tumor vaccine.\", 'Transgenic mice that develop spontaneous prostate cancer (TRAMP) which also express a unique tumor associated antigen (Influenza hemagglutinin) under the control of a prostate-specific promoter were given local RT in combination with immunotherapy. The immunological outcome of this combinatorial strategy was assayed by monitoring the effector response of adoptively transferred, prostate-specific CD4 T cells.', 'Neither RT nor immunotherapy alone was capable of priming an anti-tumor immune response in animals with evolving tumors. The combination of immunotherapy with RT resulted in anti-tumor T cell activation--this effect was profoundly dependent on the relative timing of RT and immunotherapy. Anti-tumor immune responses occurred when immunotherapy was administered 3-5 weeks post-RT, but such responses were undetectable when immunotherapy was administered either earlier (peri-radiotherapy) or later.",
            "output": [
                "Does radiotherapy augment the immune response to prostate cancer in a time-dependent manner?"
            ]
        },
        {
            "id": "task847-0418b49553f949ae8fca248daf15db2c",
            "input": "Patients generally die of cancer after the failure of current therapies to eliminate residual disease. A subpopulation of tumor cells, termed cancer stem cells (CSC), appears uniquely able to fuel the growth of phenotypically and histologically diverse tumors. It has been proposed, therefore, that failure to effectively treat cancer may in part be due to preferential resistance of these CSC to chemotherapeutic agents. The subpopulation of human colorectal tumor cells with an ESA(+)CD44(+) phenotype are uniquely responsible for tumorigenesis and have the capacity to generate heterogeneous tumors in a xenograft setting (i.e. CoCSC). We hypothesized that if non-tumorigenic cells are more susceptible to chemotherapeutic agents, then residual tumors might be expected to contain a higher frequency of CoCSC.', 'Xenogeneic tumors initiated with CoCSC were allowed to reach approximately 400 mm(3), at which point mice were randomized and chemotherapeutic regimens involving cyclophosphamide or Irinotecan were initiated. Data from individual tumor phenotypic analysis and serial transplants performed in limiting dilution show that residual tumors are enriched for cells with the CoCSC phenotype and have increased tumorigenic cell frequency. Moreover, the inherent ability of residual CoCSC to generate tumors appears preserved. Aldehyde dehydrogenase 1 gene expression and enzymatic activity are elevated in CoCSC and using an in vitro culture system that maintains CoCSC as demonstrated by serial transplants and lentiviral marking of single cell-derived clones, we further show that ALDH1 enzymatic activity is a major mediator of resistance to cyclophosphamide: a classical chemotherapeutic agent.",
            "output": [
                "Are colorectal cancer stem cells enriched in xenogeneic tumors following chemotherapy?"
            ]
        },
        {
            "id": "task847-c78f8300113a471fbe1c001fd3cbc259",
            "input": "It was recently reported that protein disulfide isomerase (PDI) stimulates factor X (FX) activation by factor VIIa (FVIIa) bound to soluble tissue factor (sTF) in a purified system and that PDI may be responsible for activating cellular tissue factor (TF) and switching it between its roles in blood coagulation and cellular signalling. This study further investigates the former effect of PDI.', 'FX activations by FVIIa-sTF(1-219) were carried out in the presence of different forms of PDI, with annexin V or detergent present in the system and using various forms of FVIIa and FX. In addition, FVIIa-lipidated TF was used as the FX activator.', 'Recombinant human PDI did not influence FX activation by FVIIa-sTF(1-219), whereas PDI purified from bovine liver enhanced the activation rate in a dose-dependent manner. The inclusion of annexin V or detergent abolished the stimulatory effect. Removal of the phospholipid-interactive gamma-carboxyglutamic acid (Gla)-containing domain from either FVIIa or FX obliterated the bovine PDI-induced enhancement of FX activation, as did the introduction of F4A or L8A mutation in FVIIa. The presence of 25 nM bovine PDI lowered the apparent K(m) for FX from far above 10 microM to 1-2 microM. No PDI effect was seen when FVIIa-lipidated TF was the FX activator.",
            "output": [
                "Does protein disulfide isomerase have no stimulatory chaperone effect on factor X activation by factor VIIa-soluble tissue factor?"
            ]
        },
        {
            "id": "task847-78931e1a2cb446788c51d50f2d00dc46",
            "input": "We evaluated assays for the measurement of acute phase protein levels in plasma for their usefulness to identify sensitively an inflammatory response to active cytomegalovirus CMV infection in HIV-infected patients.', 'Plasma samples were collected from 28 CMV-seropositive patients with advanced HIV-infection (CD4-cell count <200/microl) before commencement of antiretroviral therapy. Sensitivity, specificity, and area under receiver operating characteristic curve for the selected acute phase protein assays (haptoglobin, fibronectin, high-sensitivity C-reactive protein (hs-CRP), human interleukin-6, serum amyloid A (SAA), and human lipopolysacharide binding protein) were compared with results of a CMV-specific PCR assay.', \"CMV viremia was detectable in 8/28 patients. Levels of SAA correlated well with those of hs-CRP (r' = 0.439, P = 0.019 (Spearman rank correlation)). Levels of SAA >3 mg/L discriminated with 100% sensitivity and 40% specificity between HIV-infected patients with and without active CMV infection. Sensitivity of fibronectin was 100% and specificity 15% at a threshold-value corresponding with the lower limit of normal values as defined by the manufacturer of the assay (>29 mg/dL). Levels of the other acute phase proteins evaluated did not correlate with detection of CMV-DNA in plasma.",
            "output": [
                "Is aymptomatic CMV viremia associated with increased levels of serum amyloid A in patients with advanced HIV-infection?"
            ]
        },
        {
            "id": "task847-fb075323ebbc41c6933ad92f1e924328",
            "input": "Studies on the safety of aprotinin in coronary artery surgery have given conflicting results. Therefore, we studied the possible link between perioperative aprotinin treatment and renal dysfunction in patients undergoing first-time coronary surgery with a high risk of bleeding.', 'We performed a matched cohort study, comparing 200 patients receiving high-dose aprotinin with 200 patients receiving tranexamic acid during primary isolated coronary surgery. Patients were matched according to age, sex, and presence of acute coronary syndrome. Primary outcome was fractional change in creatinine clearance. Secondary outcomes were other evaluations of postoperative renal function, mortality, stroke, reoperation for bleeding, and transfusion requirements.', 'The groups were similar in baseline characteristics except that triple-vessel disease and history of myocardial infarction were more prevalent in the aprotinin group. No significant differences were found in fractional change in creatinine clearance (-11% versus -12%, medians, p = 0.75) or any other assessments of postoperative renal function between the tranexamic acid and the aprotinin group. Adverse event rates were similar: early mortality (3.5% versus 4.5%, p = 0.80), stroke (1.5% versus 2%, p = 1.0), reoperation for bleeding (3.5% versus 2.5%, p = 0.77), and 5-year survival (87% versus 84%, p = 0.17). Patients in the aprotinin group received fewer transfusions (48% versus 60.5%, p = 0.02), fewer units of packed red blood cells (2.0 versus 1.4, p = 0.02) and plasma (1.3 versus 0.5, p < 0.001), but more units of platelets (0.1 versus 0.2, p = 0.02).",
            "output": [
                "Is aprotinin associated with postoperative renal impairment after primary coronary surgery?"
            ]
        },
        {
            "id": "task847-d4ed530494264a57b394e5112bb42984",
            "input": "To assess whether actigraphy is sensitive to benzodiazepine-induced changes in cognitive and psychomotor performance and sleep.', 'Healthy young volunteers (n = 23; 11 males), were randomised to a double-blind, placebo-controlled, crossover trial. Actigraphy was used to record motor activity continuously. Following dosing at 18.00 h with 2.5 mg lorazepam (LZP), psychomotor and cognitive assessments were made at hourly intervals post-dose for 4 h and after sleep at 14.5 h post-dose.', 'Activity levels were significantly reduced after LZP for 5 h post-dose (p = 0.0104), during sleep (5-13 h) (p < 0.02) and the following morning, 13-14.5 h post-dose (p < 0.02). At the same time cognitive and psychomotor performance was also significantly impaired (p < 0.05). LZP also significantly increased actigraphic sleep efficiency and sleep per cent (p < 0.02).",
            "output": [
                "Does benzodiazepine-induced reduction in activity mirror decrements in cognitive and psychomotor performance?"
            ]
        },
        {
            "id": "task847-378389e9cc604486975f39cba55c64b0",
            "input": "A profound reduction of spontaneous as well as stimulated GH secretion has been consistently observed in obesity. Dopamine promotes GH release through activation of dopamine D2 receptors (D2Rs). Dopamine D2R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that impaired dopamine D2R signaling is mechanistically involved in the deficient GH secretion associated with obesity.', 'To test this hypothesis, we studied the effect of short-term bromocriptine (B) (a D2R agonist) treatment on spontaneous 24-h GH secretion in obese women, while body weight and caloric intake remained constant.', 'This was a prospective, fixed order, cross-over study.', 'The study was performed in the Clinical Research Center at Leiden University Medical Center.', 'There were 18 healthy obese women (body mass index 33.2 +/- 0.6 kg/m2) studied twice in the early follicular phase of their menstrual cycle.', 'Eight days of treatment with B and placebo (Pl) was performed.', 'Blood was collected during 24 h at 10-min intervals for determination of GH concentrations. GH secretion parameters were calculated using deconvolution analysis.', 'Short-term treatment with B significantly enhanced diurnal GH secretion (Pl 121.4 +/- 16.4 vs. B 155.4 +/- 15.2 microg/liter(volume of distribution).24 h; P = 0.01), whereas IGF-I concentrations remained constant (Pl 22.4 +/- 2.4 vs. B 21.8 +/- 1.6 nmol/liter; P = 0.928).",
            "output": [
                "Does short-term treatment with bromocriptine improve impaired circadian growth hormone secretion in obese premenopausal women?"
            ]
        },
        {
            "id": "task847-05f2c2f6ff5341fbaad169bd63d521e8",
            "input": "Low sex hormone levels have been associated with the metabolic syndrome (MetS).', 'Our objective was to determine whether the association between sex hormone levels and MetS varies by race/ethnicity among men and to investigate the relationship of sex hormones and individual components of MetS.', 'We conducted a population-based observational survey.', 'A multistage stratified design was used to recruit a random sample of 2301 racially/ethnically diverse men age 30-79 yr. Blood samples were obtained on 1899 men. Analyses were conducted on 1885 men with complete data on total testosterone (T), free T, and SHBG.', 'There were no interventions.', 'MetS was defined using a modification of the Adult Treatment Panel III guidelines. The association between MetS and sex hormone levels was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models.', 'A strong inverse association was observed, in both bivariate and multivariate analyses, between hormone levels and MetS. The odds of MetS increased about two-fold with a 1 sd decrease in hormone levels. The association between sex hormones and MetS was statistically significant across racial/ethnic groups. Although the magnitude of this association was largest among White men, racial/ethnic differences were not statistically significant. The strength of the association of sex hormones with individual components of MetS varied; stronger associations were observed with waist circumference and dyslipidemia and more modest associations with diabetes and elevated blood sugar.",
            "output": [
                "Is inverse association of testosterone and the metabolic syndrome in men consistent across race and ethnic groups?"
            ]
        },
        {
            "id": "task847-c398019fb38c44f18422a0a9c68028fb",
            "input": "Uterine leiomyomas are the most frequent benign tumors during reproductive age. Whether intramural leiomyomas cause infertility and should be removed is controversial because no study has addressed the underlying mechanism of infertility.', 'The objective of the study was to test the effect of intramural leiomyomas on endometrial function by comparing gene during the window of implantation and implantation in an oocyte donation program, in which the quality of the embryos replaced is similar and the endocrine environment of the endometrium is standardized by exogenous steroids.', 'Human endometria of women with single intramural leiomyomas (group A, <5 cm and group B, > or =5 cm) and controls (group C) were collected on day LH+7 and processed for histology and gene expression analysis, using different methods and validated by quantitative RT-PCR. To compare in vitro fertilization outcome, a total of 1035 cases from our oocyte donation database were included, comprising patients with one fibroid less than 5 cm (A1, n = 532); two leiomyomas less than 5 cm (A2, n = 128); three or more leiomyomas less than 5 cm (A3, n = 125); one fibroid 5 cm or greater (B, n = 22); and two control groups: C1 (n = 93), women with previous myomectomy; and C2 (n = 135), women without uterine pathology treated on the same dates as C1.', \"There was a strong positive and negative correlation in the expression profile of 69 genes according to the leiomyomas's size, but only three of the 25 genes related to the window of implantation were dysregulated. Term pregnancy rates after oocyte donation were 36.9, 34.1, 39.0, 36.4, 39.2, and 42.6% (P = 0.769) among the established groups. Similarly, no correlation between implantation and miscarriage with leiomyoma number and size was found.",
            "output": [
                "Are endometrial receptivity and implantation affected by the presence of uterine intramural leiomyomas : a clinical and functional genomics analysis?"
            ]
        },
        {
            "id": "task847-18d6424794db4565a590f1b7f09adb2d",
            "input": "Polycystic ovary syndrome (PCOS) is a common endocrinopathy of uncertain etiology but with strong evidence for a genetic contribution.', 'The objective of the study was to test the hypothesis that the typical polycystic ovarian morphology is a marker of inherited biochemical features in families of women with PCOS.', 'A study of probands with PCOS and their sisters.', 'Patients included 125 probands and 214 sisters. All probands had PCOS, defined by symptoms of anovulation and/or hyperandrogenism with polycystic ovaries on ultrasound. Affected sisters were defined by polycystic ovaries, regardless of symptoms, and unaffected sisters defined by normal ovarian morphology.', 'This was a clinic-based study.', 'Clinical, endocrine, and metabolic features in the various groups were compared, and estimates of broad-sense heritability were obtained using the quantitative transmission disequilibrium test.', 'Although affected sisters had fewer symptoms than probands (30% had no symptoms of PCOS), serum testosterone, androstenedione, LH, and fasting insulin and insulin sensitivity were similar in the two groups with polycystic ovaries but significantly different from those in unaffected sisters or controls. We observed moderate to high heritabilities for all traits studied in affected sister pairs, whereas heritabilities calculated from discordant siblings were substantially lower.",
            "output": [
                "Is ovarian morphology a marker of heritable biochemical traits in sisters with polycystic ovaries?"
            ]
        },
        {
            "id": "task847-d70b037a856e4f49a0f993d5ba44f843",
            "input": "Many obese subjects show relevant psychological distress. The aims of this study were to assess the psychopathological and clinical features of a sample of overweight or obese subjects seeking weight loss treatment and to evaluate the possible, significant associations between the levels of overweight and the specific and general eating disorder psychopathology.', 'A total of 397 consecutive overweight (body mass index > or =25 kg/m(2)) patients seeking treatment for weight loss at the Outpatient Clinic for Obesity of the University of Florence were studied. The prevalence of binge eating disorder was assessed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. All subjects were assessed through the self-report version of the Eating Disorder Examination Questionnaire, the Beck Depression Inventory, and the State-Trait Anxiety Inventory.', 'The current prevalence of binge eating disorder was 24.2%; 35% of the subjects were overweight during childhood. High prevalence rates of clinical significant depressive (38%) and anxious (71.5%) symptoms were observed. Binge eating disorder, the severity of specific eating disorder psychopathology, and depressive and anxious symptoms were not associated with the severity of overweight.",
            "output": [
                "Does eating disorder psychopathology predict the overweight severity in subjects seeking weight loss treatment?"
            ]
        },
        {
            "id": "task847-7a33fb0523fa410cb02f00a1cd99a4e7",
            "input": "Cilostazol, a selective inhibitor of PDE3, has a protective effect on endothelium after ischemic vascular damage, through production of nitric oxide (NO). The purpose of the present study was to clarify the molecular mechanisms underlying the preventive effect of treatment with cilostazol on oxidative stress-induced premature senescence in human endothelial cells.', 'Prematurely senescent human umbilical vein endothelial cells (HUVECs) were induced by treatment with hydrogen peroxide (H(2)O(2)) as judged by senescence-associated beta-galactosidase assay (SA-betagal), cell morphological appearance, and plasminogen activator inhibitor-1 (PAI-1) expression. Treatment with H(2)O(2) caused 93% of the cells to be SA-betagal positive, whereas 46% of cilostazol (100 micromol/L)-treated cells were positive. HUVECs treated with other cAMP-elevating agents and DETA-NO showed a reduction of SA-betagal-positive cells as well. Cilostazol increased phosphorylation of Akt at Ser(473) and of endothelial nitric oxide synthase (eNOS) at Ser(1177), with a dose-dependent increase in Sirt1 expression. Moreover, the effect of cilostazol on premature senescence was abrogated through inhibition of Sirt1.",
            "output": [
                "Does cilostazol inhibit oxidative stress-induced premature senescence via upregulation of Sirt1 in human endothelial cells?"
            ]
        },
        {
            "id": "task847-b0d25b8f53804d1589e3d5d349a82e39",
            "input": "Subclinical hypercortisolism (SH) is suggested to exert a deleterious effect on bone. This effect and the role of gonadal status in male subjects are not fully elucidated. We evaluated bone mineral density (BMD) and prevalence of vertebral fractures in eugonadal male subjects with adrenal incidentalomas (AI) and without SH.', 'This 12-month observational multicentre study was performed between January and December 2006 on inpatient basis in three referral Italian centres.', 'Eighty-eight consecutive eugonadal male patients with AI and 90 matched control subjects were studied.', 'All subjects underwent the determination of BMD by dual-energy X-ray absorptiometry at lumbar spine (LS) and femoral neck (FN), and spinal radiograph. In AI patients SH was diagnosed in the presence of two of the following: urinary free cortisol > 193.1 nmol/l, cortisol after 1 mg dexamethasone suppression test > 82.8 nmol/l, ACTH levels < 2.2 pmol/l.', 'As compared to patients without SH (SH-, n = 66) and controls, patients with SH (SH+, n = 22) had lower BMD at LS (Z-score: SH+, -1.04 +/- 1.84; SH-, 0.19 +/- 1.34, Controls 0.20 +/- 1.28, P = 0.001 and FN (Z-score: SH+, -0.63 +/- 1.01; SH-, 0.01 +/- 1.01, Controls 0.26 +/- 1.06, P = 0.002) and higher prevalence of fractures (SH+, 72.7%; SH-, 21.2%, Controls 20.0%, P = 0.0001). Multivariable analyses showed that SH was associated to BMD at LS (beta = -0.378, P = 0.0001) and vertebral fractures (OR = 7.81, 95% CI 1.96-31.17, P = 0.004).",
            "output": [
                "Do eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures?"
            ]
        },
        {
            "id": "task847-7293ebbbbf11489ea4fc62fdbf47c4c6",
            "input": "Cirrhosis is associated with prominent changes in sinusoidal structure and function. Although the resident pericyte in liver, the hepatic stellate cell (HSC), is well characterized in the process of fibrogenesis, signaling pathways that regulate HSC vascular function are less developed. Because pericyte populations outside the liver are increasingly being recognized as a key cell type for angiogenesis and changes in vascular structure, in this study, we explore new HSC-signaling pathways that regulate sinusoidal structure and function.', 'Real-time video microscopy and quantitative software analysis of vascular tube formation were used to measure HSC angiogenesis in vitro. Platelet-derived growth factor (PDGF) and ephrin-signaling pathways were modulated using molecular and pharmacologic techniques. Complementary whole animal studies were performed to correlate in vitro findings with pericyte functions in vivo.', 'We show that PDGF promotes a phenotype of HSC evidenced by enhanced HSC-driven vascular tube formation in vitro and enhanced HSC coverage of sinusoids in vivo. This angiogenic phenotype modulates specific pericyte vascular functions including permeability and pressure regulation. Furthermore, we identify a key role for ephrin-B2 as a downstream effector of PDGF signaling.",
            "output": [
                "Does platelet-derived growth factor signaling through ephrin-b2 regulate hepatic vascular structure and function?"
            ]
        },
        {
            "id": "task847-2b5f802349c64a4b979a38be075fc90a",
            "input": "pulmonary rehabilitation (PR) improves health status and exercise tolerance, but not respiratory function in patients with chronic obstructive pulmonary disease (COPD). Our objective was to identify predictors of improvement in the 6-min walked distance (6'WD) in elderly COPD patients after PR.\", \"this was a prospective observational study performed in an ambulatory rehabilitation setting. We enrolled 74 patients aged 65-83 years (mean: 74.2, SD: 4.4) with stable COPD in GOLD stage 3-4. About half (45.6%) of them had a basal O(2) saturation of 90% or less. After a baseline multi-dimensional assessment, patients underwent a 20-session rehabilitation cycle including training of the upper and lower extremities, and respiratory exercises, along with education sessions. The difference between final and basal 6'WD was expressed as a per cent of the basal value (6'WD gain). Patients were divided into two groups according to whether the 6'WD gain was above or under the 75th percentile, corresponding to 33% gain.\", \"patients whose 6'WD improved more had lower baseline forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) (46.0 versus 52.2%, P = 0.03) and baseline 6'WD, both as an absolute value (329.5 versus 408.9 m, P = 0.01) and as a per cent of the predicted (71.1 versus 93.5%, P = 0.002). After correction for potential confounders, baseline 6'WD was the only variable associated with the outcome (OR for 5% increments: 0.79; 95% CI 0.65-0.95).",
            "output": [
                "Does age hamper the response to pulmonary rehabilitation of COPD patients?"
            ]
        },
        {
            "id": "task847-7a71c9e8b79d4d39acbb6ecb29a76749",
            "input": "Patients with ulcerative colitis have a high risk for the development of colorectal cancer. To understand the molecular mechanisms of the carcinogenesis process of ulcerative colitis-associated colorectal cancer, the genetic alterations in inflamed or neoplastic colon epithelium in ulcerative colitis were analyzed.', 'Fifty-seven patients with ulcerative colitis were enrolled in this study. Specimens were obtained from the patients randomly at six colonic sites. Each patient was histologically classified according to the worst pathologic finding into cancer, dysplasia, indefinite, and normal cases. Microsatellite instability, mutations of target genes, hypermethylation of the hMLH1 promoter region, and mismatch repair protein expression were analyzed.', 'High-microsatellite instability was found in 4 of 11 cancer cases (36 percent), 5 of 15 dysplasia cases (33 percent), 5 of 11 indefinite cases (45 percent), and none of 20 normal cases (0 percent). A significant correlation was found between the malignant potential and high-microsatellite instability. A frameshift mutation of transforming growth factor beta receptor Type II (TGFbetaRII) was significantly correlated with worsening histologic grade. High-microsatellite instability was significantly associated with hMLH1 hypermethylation and loss of hMSH2 expression.",
            "output": [
                "Is ulcerative colitis-associated colorectal cancer frequently associated with the microsatellite instability pathway?"
            ]
        },
        {
            "id": "task847-7314da63c4e04f24bc60b2e41f8ef926",
            "input": "To assist in the development of preventive strategies, we studied whether the neighbourhood environment or modifiable behavioural parameters, including cardiorespiratory fitness (CRF) and physical activity (PA), are independently associated with obesity and metabolic risk markers in children.', 'We carried out a cross-sectional analysis of 502 randomly selected first and fifth grade urban and rural Swiss schoolchildren with regard to CRF, PA and the neighbourhood (rural vs urban) environment. Outcome measures included BMI, sum of four skinfold thicknesses, homeostasis model assessment of insulin resistance (HOMA-IR) and a standardised clustered metabolic risk score.', 'CRF and PA (especially total PA, but also the time spent engaged in light and in moderate and vigorous intensity PA) were inversely associated with measures of obesity, HOMA-IR and the metabolic risk score, independently of each other, and of sociodemographic and nutritional parameters, media use, sleep duration, BMI and the neighbourhood environment (all p < 0.05). Children living in a rural environment were more physically active and had higher CRF values and reduced HOMA-IR and metabolic risk scores compared with children living in an urban environment (all p < 0.05). These differences in cardiovascular risk factors persisted after adjustment for CRF, total PA and BMI.",
            "output": [
                "Are reduced cardiorespiratory fitness , low physical activity and an urban environment independently associated with increased cardiovascular risk in children?"
            ]
        },
        {
            "id": "task847-982c9a75a6b34a4294a773a9df3aa77b",
            "input": "Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported.', 'The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner.', 'There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups.",
            "output": [
                "Does icodextrin impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients : a 2-year multicentre , comparative , prospective cohort study?"
            ]
        },
        {
            "id": "task847-180f728dd24f40e1a65a4fc3ef40484a",
            "input": "The objective of this study was to determine the quantitative influence of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP 2C9) polymorphisms on warfarin dose requirements in Turkish patients.', 'A total of 205 patients taking warfarin for >2 months were enrolled in the study. Deoxyribonucleic acid (DNA) samples from these patients were genotyped for polymorphisms in VKORC1 and CYP2C9 genes. A linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on mean warfarin dose requirements.', 'The VKORC1 promoter polymorphism (3673 G>A) was associated with differences in weekly mean varfarin dose: for GG genotype the dose was 43.18 mg/week, for GA genotype 33.78 mg/week and for AA genoype 25.83 mg/week (P < 0.0001). Patients who carried VKORC1 and CYP2C9 variants needed a 40% lower mean weekly warfarin dose compared to wild types. Variables associated with lower warfarin dose requirements were VKORC1 3673 AA or GA genotype (both P < 0.0001), one or two CYP2C9 variant alleles (both P < 0.0001), increasing age (P < 0.0001) and non-indication of venous thromboembolism for warfarin therapy (P = 0.002).",
            "output": [
                "Are vKORC1 and CYP2C9 polymorphisms associated with warfarin dose requirements in Turkish patients?"
            ]
        },
        {
            "id": "task847-02d55e8e764f4b9986cb39c0a892e531",
            "input": "To evaluate the effect of 3-month kale (Brassica oleracea acephala) juice supplementation on coronary artery disease risk factors among hypercholesterolemic men.', 'Thirty-two men with hypercholesterolemia (> 200 mg/dL) were recruited after annual health examinations among the faculty and staff at university. The subjects consumed 150 mL of kale juice per day for a 12-week intervention period. Dietary and anthropometric assessments were performed and blood samples were collected to evaluate biochemical profiles before and after supplementation.', 'Serum concentrations of HDL-cholesterol, and HDL- to LDL-cholesterol ratio were significantly increased by 27% (P<0.0001) and 52% (P<0.0001), respectively. The LDL-cholesterol concentration and the atherogenic index were significantly reduced by 10% (P=0.0007) and 24.2% (P<0.0001), respectively without affecting body mass index, waist and hip circumferences, or nutrient intakes after three months of supplementation. While there was no difference in the concentration of malondialdehyde, significant increase in glutathione peroxidase activity (P=0.0005) were accompanied by a significant increase in the serum selenium level (P=0.0132). It was also found that the responses of these risk factors to kale juice administration were dependent on smoking status.",
            "output": [
                "Does kale juice improve coronary artery disease risk factors in hypercholesterolemic men?"
            ]
        },
        {
            "id": "task847-67ff69bff7bc494a90da3bc7d7904cdf",
            "input": "To determine the role of the lens and the lens capsule in the three-dimensional architecture of the ciliary muscle at rest and during accommodation, in live rhesus monkeys and in histologic sections, by removing the entire lens, or only the lens nucleus and cortex, while leaving the posterior capsule in place.', 'In 15 rhesus monkey eyes, aged 6 to 27 years, accommodation was induced by central stimulation of the Edinger-Westphal nucleus before and after intra- or extracapsular lens extraction (ICLE, ECLE). Forward ciliary body movement and ciliary body width were measured by ultrasound biomicroscopy (UBM, 50 MHz). The monkeys were then killed, the eyes were examined morphologically in 1-microm sections, and the shape of the ciliary muscle was compared with that obtained from UBM images.', 'The shape of the ciliary muscle in eyes undergoing ECLE (n = 5) did not differ from that in control eyes. In contrast, after ICLE (n = 10), accommodative forward ciliary body movement (P < 0.01) and thickness were decreased (P < 0.001), length was increased (P = 0.058), and the inner apex was located more posteriorly than in control eyes (P < 0.005). Histologic and in vivo data were similar and showed that the ciliary muscle maintained its triangular shape only if the lens capsule (with or without the lens substance) was present.",
            "output": [
                "Is surgical intervention and accommodative responses , II : forward ciliary body accommodative movement facilitated by zonular attachments to the lens capsule?"
            ]
        },
        {
            "id": "task847-6a3d3a9a1a1045d79c672c6e20ed24a5",
            "input": "To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa.', 'In 316 patients with typical forms of retinitis pigmentosa, visual acuity was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, macular cysts were detected with optical coherence tomography (OCT), and retinal thicknesses was quantified by OCT. The FREQ, LOGISTIC, and GENMOD procedures of SAS (SAS Institute, Cary, NC) were used to evaluate possible risk factors for cyst prevalence, and the MIXED procedure was used to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula.', 'Macular cysts were found in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (P = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (P = 0.038) and within a parafoveal ring spanning an eccentricity of 5 degrees to 10 degrees from the foveal center (P = 0.004).",
            "output": [
                "Is visual acuity related to parafoveal retinal thickness in patients with retinitis pigmentosa and macular cysts?"
            ]
        },
        {
            "id": "task847-bdebe0d647054a00acf6d0a9694a5ea2",
            "input": "To compare the circulating concentrations of the acute-phase protein serum amyloid A (SAA) in lean, overweight, and obese children and adolescents and analyze the influence of body fat.', 'A total of 63 children and adolescents (65% girls) with an average age of 12.1 +/- 2.7 years (range, 6 to 18 years) were included in the study. Each child was classified on the basis of age- and sex-specific body mass index (BMI) percentile as normal weight (BMI <85th percentile; n = 17), overweight (BMI >/=85th and <95th percentiles; n = 26), or obese (BMI >/=95th percentile; n = 20). Body fat was estimated by air-displacement plethysmography.', 'Both overweight and obese children exhibited significantly increased circulating SAA concentrations (log SAA: lean, 0.66 +/- 0.20; overweight, 0.83 +/- 0.29; obese, 0.96 +/- 0.21; P = .002) compared with the lean children. Significant correlations were found between log SAA and body fat (r = 0.48; P < .0001). In multiple linear regression analysis, log C-reactive protein (CRP) (P = .014) and body fat (P = .031) emerged as significant predictors of log SAA.",
            "output": [
                "Is serum Amyloid A concentration increased in obese children and adolescents?"
            ]
        },
        {
            "id": "task847-b90ec1b9e9974cbabedf99f1dc5c8bf6",
            "input": "Neurovirulent Venezuelan equine encephalitis virus (VEEV) causes lethal encephalitis in equines and is transmitted to humans by mosquitoes. VEEV is highly infectious when transmitted by aerosol and has been developed as a bio-warfare agent, making it an important pathogen to study from a military and civilian standpoint. Molecular mechanisms of VEE pathogenesis are poorly understood. To study these, the gene expression profile of VEEV infected mouse brains was investigated. Changes in gene expression were correlated with histological changes in the brain. In addition, a molecular framework of changes in gene expression associated with progression of the disease was studied.', 'Our results demonstrate that genes related to important immune pathways such as antigen presentation, inflammation, apoptosis and response to virus (Cxcl10, CxCl11, Ccl5, Ifr7, Ifi27 Oas1b, Fcerg1,Mif, Clusterin and MHC class II) were upregulated as a result of virus infection. The number of over-expressed genes (>1.5-fold level) increased as the disease progressed (from 197, 296, 400, to 1086 at 24, 48, 72 and 96 hours post infection, respectively).",
            "output": [
                "Does venezuelan equine encephalitis virus infection cause modulation of inflammatory and immune response genes in mouse brain?"
            ]
        },
        {
            "id": "task847-55f3a882ecf14561b89e3d4a0185ab9b",
            "input": "Doxorubicin is a cytotoxic drug with potential for severe myelosuppression that is highly variable and poorly predictable.', 'We correlated CBR1 and CBR3 genotypes with the pharmacokinetics and pharmacodynamics of doxorubicin in 101 Southeast Asian breast cancer patients receiving first-line doxorubicin.', 'A common CBR3 11G>A variant was associated with lower doxorubicinol area under the concentration-time curve (AUC)/doxorubicin AUC metabolite ratio (P=0.009, GG vs. AA; trend test, P=0.004), lower CBR3 expression in breast tumor tissue (P=0.001, GG vs. AA), greater tumor reduction (P=0.015, GG vs. AA), and greater percentage reduction of leukocyte and platelet counts at nadir (trend test, P < or = 0.03). Chinese and Malays had higher frequency of the CBR3 11G>A variant than Indians (P < or = 0.002). Another variant CBR3 730G>A was associated with higher doxorubicinol AUC (P=0.009, GG vs. AA) and CBR3 expression in breast tumor tissue (P=0.001, GG vs AA).",
            "output": [
                "Does genotype of human carbonyl reductase CBR3 correlate with doxorubicin disposition and toxicity?"
            ]
        },
        {
            "id": "task847-c1ae0393abb649d0b6c7e7fc3b1357c0",
            "input": "The GNB3 C825T polymorphism has been shown to affect lipid parameters, atherosclerosis progression, and incidence of myocardial infarction (MI). Therefore, we assessed whether the effectiveness of statins in reducing the risk of MI was modified by the GNB3 C825T polymorphism.', 'In a population-based registry of pharmacy records linked to hospital discharge records (PHARMO), we used a nested case-control design. We selected patients hospitalized for MI as cases if they used antihypertensive drugs and had a diagnosis of hypercholesterolemia before their first MI. Controls met the same eligibility criteria, but were not hospitalized for MI. Logistic regression analysis was used to calculate odds ratios (OR) and synergy index with corresponding 95% confidence intervals (CI), and to adjust for potential confounding factors.', 'We included 459 cases and 1805 controls. The risk of MI was significantly lower among participants exposed to statins compared with participants not exposed to statins (adjusted OR: 0.37, 95% CI: 0.29-0.47). The GNB3T allele was associated with a reduced risk of MI (adjusted OR: 0.74, 95% CI: 0.60-0.92). Among homozygous wild-type (CC) individuals (n=1119), exposure to statins was associated with a lower risk of MI (OR: 0.48, 95% CI: 0.34-0.67). However, T allele carriers (CT and TT) who used statins had an even stronger reduced risk of MI (OR: 0.27, 95% CI: 0.19-0.39). Overall, the interaction between exposure to statins and the GNB3 C825T polymorphism was significantly increased on the multiplicative scale (synergy index: 1.67, 95% CI: 1.06-2.65).",
            "output": [
                "Is effectiveness of statins in the reduction of the risk of myocardial infarction modified by the GNB3 C825T variant?"
            ]
        },
        {
            "id": "task847-e47a30ab0ff744339bdaaaa77cf789a8",
            "input": "Sympathetic nervous system hyperactivity promotes vascular disorders by its catabolic effects and by increasing arterial blood pressure. Levodopa-derived dopamine modulates sympathetic overactivity and is known to reduce blood pressure, but its effects on glucose and lipid metabolism have not been studied in large series of patients.', 'We retrospectively examined 483 consecutive parkinsonian patients, admitted to a single institute between 1970 and 1987, before statins were available. We compared risk factors for vascular disease in the 305 who were on levodopa with the 178 who had never received the drug.', 'On admission levodopa-treated patients had significantly lower plasma levels of triglycerides, total cholesterol and lipids, and lower frequency of diabetes and hypertension than untreated patients. Mean body mass index, resting blood pressure, fasting plasma glucose, and smoking did not differ between the groups. A year after enrollment 160 patients were re-hospitalized; of these 63 had started levodopa during first hospitalization. In these new levodopa users total cholesterol, triglycerides and lipids had reduced to levels comparable with those of longer-term levodopa users.",
            "output": [
                "Does sympathetic modulation by levodopa reduce vascular risk factors in Parkinson disease?"
            ]
        },
        {
            "id": "task847-0c50962978ed45a9a5faf2c8af96bcbc",
            "input": ": Trauma center physicians need to know the patient's prognosis to make appropriate clinical decisions when they take over the care of a transferred patient. We sought to compare the survival of injured patients after transfer to a trauma center with survival from a comparable time after injury among patients who had been admitted to the trauma center directly from the scene of injury.\", ': Study included 2,867 patients 18 years to 84 years of age with at least one Abbreviated Injury Scale score >/=3 injury transferred to a trauma center and 7,570 patients admitted directly to a trauma center. The outcome was death within one year after injury. Cox proportional hazards model for death was used accounting for time since injury, adjusted for age group, gender, injury severity, injury mechanism, and comorbidities.', ': Overall, there was almost no increase in the adjusted risk of death for transfer patients in the year after injury [hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.78, 1.27]. The adjusted risk of death was higher in transfer patients than nontransfer patients between 50 days and 365 days after injury (HR 1.28, 95% CI 0.79, 2.07), but not within the first 50 days (HR 0.95, 95% CI 0.76, 1.18). However these modest differences in survival within each period were not statistically significant.",
            "output": [
                "Do outcomes of trauma patients after transfer to a level I trauma center?"
            ]
        },
        {
            "id": "task847-ceaa1d75c9ab41f6a7739f37652b4c17",
            "input": "Although the unipolar depression-eating disorder comorbidity is adequately documented, examination of the role of depressive personality styles in eating disorders is relatively scarce.', 'Associations between depressive symptoms, depressive risk and resilience (i.e., dependency, self-criticism, and sense of efficacy), and eating disorder symptoms (as measured by the Eating Disorder Inventory-2) were examinedin inpatient adolescent females (N = 81).', 'Self-criticism emerged as independent, robust, and strong predictor of eating disorder symptoms.",
            "output": [
                "Is self-criticism a key predictor of eating disorder dimensions among inpatient adolescent females?"
            ]
        },
        {
            "id": "task847-93a57d94886c4f6dab956289dccf1e77",
            "input": "We sought to investigate the utility of phase-contrast diffuse optical tomography (PCDOT) for differentiation of malignant and benign breast masses in humans and to compare PCDOT with conventional diffuse optical tomography (DOT) for analysis of breast masses in humans.', 'Thirty-five breast masses were imaged in 33 patients (mean age, 51 years; range, 22-80) using PCDOT. Images characterizing the tissue refractive index, and absorption and scattering coefficients of breast masses were obtained with a finite element-based reconstruction algorithm. Theses images were then analyzed and compared with the biopsy/pathology results for all the cases examined.', 'Malignant lesions tended to have a decreased refractive index, allowing them to be discriminated from benign lesions in most cases, whereas absorption and scattering images were unable to accurately discriminate benign from malignant lesions. The sensitivity, specificity, false-positive value, and overall accuracy for refractive index imaging were 81.8%, 70.8%, 29.2%, and 74.3%, respectively. The accuracy of refractive index imaging increases with increasing patient age.",
            "output": [
                "Does phase-contrast diffuse optical tomography pilot result in the breast?"
            ]
        },
        {
            "id": "task847-0217d50f8b2d41d3a98968cb4b9323e5",
            "input": "The lycophyte Selaginella moellendorffii is a vascular plant that diverged from the fern/seed plant lineage at least 400 million years ago. Although genomic information for S. moellendorffii is starting to be produced, little is known about basic aspects of its molecular biology. In order to provide the first glimpse to the epigenetic landscape of this early divergent vascular plant, we used the methylation filtration technique. Methylation filtration genomic libraries select unmethylated DNA clones due to the presence of the methylation-dependent restriction endonuclease McrBC in the bacterial host.', 'We conducted a characterization of the DNA methylation patterns of the S. moellendorffii genome by sequencing a set of S. moellendorffii shotgun genomic clones, along with a set of methylation filtered clones. Chloroplast DNA, which is typically unmethylated, was enriched in the filtered library relative to the shotgun library, showing that there is DNA methylation in the extremely small S. moellendorffii genome. The filtered library also showed enrichment in expressed and gene-like sequences, while the highest-copy repeats were largely under-represented in this library. These results show that genes and repeats are differentially methylated in the S. moellendorffii genome, as occurs in other plants studied.",
            "output": [
                "Are the highest-copy repeats methylated in the small genome of the early divergent vascular plant Selaginella moellendorffii?"
            ]
        },
        {
            "id": "task847-62f8eeab3dc641f6b1f1184536d7f0a8",
            "input": "Histone deacetylase inhibitors (HDACi) are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB) is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel treatment modalities.', 'We show here that the HDACi Sodium Butyrate (NaB), suberoylanilide hydroxamic acid (SAHA) and Trichostatin A (TSA) strongly reduce NB cells viability. The anti-tumour activity of these HDACi involved the induction of cell cycle arrest in the G2/M phase, followed by the activation of the intrinsic apoptotic pathway, via the activation of the caspases cascade. Moreover, HDACi mediated the activation of the pro-apoptotic proteins Bid and BimEL and the inactivation of the anti-apoptotic proteins XIAP, Bcl-xL, RIP and survivin, that further enhanced the apoptotic signal. Interestingly, the activity of these apoptosis regulators was modulated by several different mechanisms, either by caspases dependent proteolytic cleavage or by degradation via the proteasome pathway. In addition, HDACi strongly impaired the hypoxia-induced secretion of VEGF by NB cells.",
            "output": [
                "Do complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells?"
            ]
        },
        {
            "id": "task847-72efd43a0be74527a11785195ee734e8",
            "input": "Chlorophyll b is a major photosynthetic pigment in green plants that is synthesized by chlorophyllide a oxygenase (CAO). The regulation of chlorophyll b biosynthesis is an important determinant for the antenna size of photosystems. Chlorophyll b synthesis is partly regulated on a transcriptional level by the expression of the CAO gene. In addition, the synthesis of chlorophyll b is strictly regulated on a protein level by the stability of the CAO enzyme. CAO consists of three domains, which are sequentially named from the N terminus as the A, B and C domains. The A domain of CAO participates in the regulation of the CAO protein stability.', 'In order to clarify the physiological function of the A domain, we constructed transgenic Arabidopsis (Arabidopsis thaliana) plants which either overexpressed the complete CAO or a truncated version of CAO lacking the A domain. The transgenic plants overexpressing the A-domain-deleted CAO accumulated an excess amount of chlorophyll b during greening. The transgenic plants which lacked the A domain either died or were obviously retarded when they were exposed to continuous light immediately after etiolation. In addition, the loss of the A domain in CAO impaired another step of chlorophyll biosynthesis, namely the conversion of divinyl-protochlorophyllide a to monovinyl protochlorophyllide a under dark conditions.",
            "output": [
                "Does loss of the N-terminal domain of chlorophyllide a oxygenase induce photodamage during greening of Arabidopsis seedlings?"
            ]
        },
        {
            "id": "task847-b7a5927d0e1c400cbc776fb66f4552dd",
            "input": "To analyse the technical quality of electronic patient records in relation to legislation and to evaluate their quality associated with the quality of consultations as rated by patients and GPs.', 'Cross-sectional study of electronic patient records.', 'Four primary healthcare (PHC) centres in Finland using three different electronic patient record systems.', 'Patient records of 175 PHC consultations by 50 GPs, rated as the best (n=86) and the worst (n=89) of a total of 2191 consultations.', 'Documentation of records compared with legislation, the general informative value of records, and its relation to the experienced quality of consultations and to the electronic system employed.', 'Reason for encounter was mentioned in 79% of cases and patient history in 32%. An acute problem was described moderately well or well in 84%, examination findings in 62%, medical problem or diagnosis in 90%, and treatment in 95% of cases. Medication was documented adequately in 38% of the cases where medication was documented. Concerning general informative value, 18% were assessed as poor, 62% as moderate, and 20% as good. No correspondence was found between experienced quality of consultation and general informative value in the patient records. The quality of patient records was found to change according to the electronic system employed.",
            "output": [
                "Does the quality of electronic patient records in Finnish primary healthcare need to be improved?"
            ]
        },
        {
            "id": "task847-10ba38f5357247599d6a737b75a30ea0",
            "input": "To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation.', 'A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate.', 'The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups.",
            "output": [
                "Does recombinant human epidermal growth factor accelerate recovery of mouse small intestinal mucosa after radiation damage?"
            ]
        },
        {
            "id": "task847-7c5ca7963d7c4a749dc18b7a154da4bf",
            "input": "We have demonstrated that administration of heparin-binding epidermal growth factor-like growth factor (HB-EGF) protects the intestines from injury. The aim of the current study was to evaluate the effect of HB-EGF gene disruption on intestinal restitution, angiogenesis, and long-term survival after intestinal ischemia/reperfusion (I/R) injury.', 'HB-EGF (-/-) and wild-type HB-EGF (+/+) littermate mice were subjected to 45 minutes of superior mesenteric artery occlusion followed by reperfusion. Functional recovery of the gut permeability barrier was evaluated with Ussing chamber studies, and microvessel density was evaluated immunohistochemically. Animal survival was evaluated using the Kaplan-Meier method.', 'Histologic damage after ischemia was significantly higher in HB-EGF (-/-) mice compared with HB-EGF (+/+) mice, associated with a significantly higher number of incompetent (nonhealed, nonresurfaced) villi indicative of delayed structural healing by restitution. HB-EGF (-/-) mice had increased intestinal permeability after intestinal I/R. HB-EGF (-/-) mice had significantly lower microvessel density at 3 and 7 days after I/R, indicating that HB-EGF gene deletion resulted in delayed onset of angiogenesis. Two-week mortality rates were significantly higher in HB-EGF (-/-) mice.",
            "output": [
                "Is heparin-binding epidermal growth factor-like growth factor gene disruption associated with delayed intestinal restitution , impaired angiogenesis , and poor survival after intestinal ischemia in mice?"
            ]
        },
        {
            "id": "task847-60dff0d271fe4ca889ae4d29d5b005db",
            "input": "Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development.', 'The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate.', 'Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus.', 'At the highest perchlorate dose, triiodothyronine (T(3)) and thyroxine (T(4)) were reduced in pups on postnatal day 21. T(4) in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T(4) were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T(3). Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose.",
            "output": [
                "Does developmental exposure to perchlorate alter synaptic transmission in hippocampus of the adult rat?"
            ]
        },
        {
            "id": "task847-2948b9b9bb40475594f8dae1b0d26dee",
            "input": "Ozone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O(3)-induced airway inflammation, but their effect on innate immune activation is unknown.', 'We used a human O(3) inhalation challenge model to examine the effectiveness of clinically relevant doses of inhaled corticosteroids on airway inflammation and markers of innate immune activation in healthy volunteers.', 'Seventeen O(3)-responsive subjects [>10% increase in the percentage of polymorphonuclear leukocytes (PMNs) in sputum, PMNs per milligram vs. baseline sputum] received placebo, or either a single therapeutic dose (0.5 mg) or a high dose (2 mg) of inhaled fluticasone proprionate (FP) 1 hr before a 3-hr O(3) challenge (0.25 ppm) on three separate occasions at least 2 weeks apart. Lung function, exhaled nitric oxide, sputum, and systemic biomarkers were assessed 1-5 hr after the O(3) challenge. To determine the effect of FP on cellular function, we assessed sputum cells from seven subjects by flow cytometry for cell-surface marker activation.', 'FP had no effect on O(3)-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O(3)-induced sputum neutrophilia by 18% and 35%, respectively. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreatment significantly reduced O(3)-induced modification of CD11b, mCD14, CD64, CD16, HLA-DR, and CD86 on sputum monocytes in a dose-dependent manner.",
            "output": [
                "Does fluticasone propionate protect against ozone-induced airway inflammation and modified immune cell activation markers in healthy volunteers?"
            ]
        },
        {
            "id": "task847-546b06fcd4a3473a9899f562de487125",
            "input": "The regular mammalian X and Y chromosomes diverged from each other at least 166 to 148 million years ago, leaving few traces of their early evolution, including degeneration of the Y chromosome and evolution of dosage compensation.', \"We studied the intriguing case of black muntjac, in which a recent X-autosome fusion and a subsequent large autosomal inversion within just the past 0.5 million years have led to inheritance patterns identical to the traditional X-Y (neo-sex chromosomes). We compared patterns of genome evolution in 35-kilobase noncoding regions and 23 gene pairs on the homologous neo-sex chromosomes. We found that neo-Y alleles have accumulated more mutations, comprising a wide variety of mutation types, which indicates cessation of recombination and is consistent with an ongoing neo-Y degeneration process. Putative deleterious mutations were observed in coding regions of eight investigated genes as well as cis-regulatory regions of two housekeeping genes. In vivo assays characterized a neo-Y insertion in the promoter of the CLTC gene that causes a significant reduction in allelic expression. A neo-Y-linked deletion in the 3'-untranslated region of gene SNX22 abolished a microRNA target site. Finally, expression analyses revealed complex patterns of expression divergence between neo-Y and neo-X alleles.",
            "output": [
                "Do neo-sex chromosomes in the black muntjac recapitulate incipient evolution of mammalian sex chromosomes?"
            ]
        },
        {
            "id": "task847-655c25abb2234a89a2a4efbd2674c757",
            "input": "To determine if human papillomaviruses (HPVs) play a role in the histogenesis of adenosarcomas of the uterine cervix.', 'Nine archival cases of primary cervical adenosarcoma were studied. The HPV status of the nine histologically proven tumours was investigated by non-isotopic in situ hybridisation (NISH) and PCR. NISH was performed using digoxigenin labelled probes to HPV types 6, 11, 16, 18, 31 and 33. PCR used GP5+/GP6+ primers to the HPV L1 gene.', 'Neither the benign epithelial components nor the malignant stromal components of the 9 neoplasms harboured nuclear NISH signals for the HPV types investigated. Amplimers of the HPV L1 gene were not detected by PCR in any of the tumours studied.",
            "output": [
                "Do human papillomaviruses play an aetiological role in M\u00fcllerian adenosarcomas of the uterine cervix?"
            ]
        },
        {
            "id": "task847-45d0fa2394dc47d78943a94732cc5674",
            "input": "Extensive apoptosis of immune cells occurs in patients with cancer, and is possibly related to immune evasion by cancer cells. The present study was designed to investigate the correlation between apoptosis levels and Fas expression in CD8+ T lymphocytes in patients with gastric cancer.', 'The expression of apoptosis markers (annexin V binding and caspase-3 activation) and the death receptor Fas in CD8+ T cells was evaluated by multicolor flow cytometry. Soluble Fas ligand (sFasL) in the sera was quantitated by enzyme-linked immunosorbent assay.', 'In patients with gastric cancer, 18.7% +/- 10.5% (mean +/- SD) of CD8+ T cells bound annexin V compared with 11.7% +/- 7.9% in normal controls (P = 0.0282). Fas expression in CD8+ T cells was higher in patients with gastric cancer (69.2% +/- 15.3%) than normal controls (50.6% +/- 15.3%) (P = 0.0051). The proportion of apoptotic CD8+ T cells was significantly correlated with Fas expression in CD8+ T cells (r = 0.409, P = 0.0214). In patients, Fas+CD8+ T cells preferentially underwent apoptosis and showed high caspase-3 activation. Moreover, the proportion of apoptotic CD8+ T cells was inversely correlated with serum levels of soluble Fas ligand (r = -0.324, P = 0.0359). Fas expression in tumor infiltrating CD8+ T cells was significantly more frequent (80.3% +/- 13.4%) than in circulating CD8+ T cells (67.9% +/- 15.5%) (P = 0.0046). A decrease in the percentage of Fas+CD8+ T cells was observed after surgery (54.1% +/- 12.8%) compared with before surgery (65.9% +/- 17.0%) (P = 0.0284).",
            "output": [
                "Is elevated Fas expression related to increased apoptosis of circulating CD8+ T cell in patients with gastric cancer?"
            ]
        },
        {
            "id": "task847-775497a3a4424678827aa6e3ba78febc",
            "input": "Galectin-1 is a major anti-inflammatory protein expressed by the placenta and immune cells that can bias the character of inflammatory responses toward the Th2 type. Galectin-1 is expressed in immune privileged sites, it can facilitate immune tolerance and tumor immune escape, and it has been successfully used for the suppression of experimental autoimmune diseases as well as graft-versus-host disease in murine models. We propose that an abnormal immune response in some pregnancy complications may be associated with changes in placental expression of galectin-1. To test this hypothesis, we studied placental galectin-1 mRNA and protein expression and localization in women with preeclampsia (PE) and in those who delivered a small-for-gestational age (SGA) neonate.', 'This cross-sectional study included pregnant women matched for gestational age at delivery in the following groups: (1) severe PE (n = 10), (2) severe PE complicated with SGA (n = 10), (3) SGA without PE (n = 10), and (4) controls (n = 10). Galectin-1 mRNA and protein were localized in placentas by in situ hybridization and immunofluorescence microscopy. Galectin-1 mRNA expression was determined by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), and galectin-1 protein content by Western blot. Non-parametric statistics were used for analysis.', '(1) In normal term placentas, galectin-1 mRNA or immunofluorescence signals were detected in the trophoblasts, villous stromal cells, Hofbauer cells, endothelial cells of the villous blood vessels, and the villous stroma. (2) Placental galectin-1 mRNA expression was significantly higher in severe PE (with or without SGA) than in controls (1.47-fold, p = 0.004; 1.44-fold, p = 0.003, respectively) and in SGA (1.68-fold, p = 0.001; 1.64-fold, p = 0.001, respectively). (3) Trophoblasts in placentas of patients with severe PE had the most intense galectin-1 immunostaining.",
            "output": [
                "Is severe preeclampsia characterized by increased placental expression of galectin-1?"
            ]
        },
        {
            "id": "task847-a3e50300ccb74ef29cadd61bccd670d8",
            "input": "To determine the level of plasma soluble CD40 ligand (sCD40L) in patients with polycystic ovary syndrome (PCOS).', 'Prospective study.', 'Baskent University School of Medicine in Turkey.', 'Thirty-one patients with PCOS and 31 non-PCOS (control) patients.', 'Determination of plasma sCD40L and homocysteine levels.', 'Plasma sCD40L, fasting glucose, fasting insulin, homeostatic model assessment insulin resistance index (HOMA-IR), LH, FSH, E(2), total T, DHEAS, total cholesterol, high- and low-density lipoprotein cholesterol, triglyceride, homocysteine, and high-sensitivity C-reactive protein (hsCRP).', 'The mean serum fasting insulin and HOMA-IR levels were significantly higher in the PCOS group. The mean serum homocysteine level was significantly higher in the PCOS group. Despite a trend for higher high-sensitivity C-reactive protein levels in the PCOS group, the difference did not reach statistical significance. The mean plasma sCD40L level in the PCOS group was significantly higher than that in the control group (5.14 +/- 3.65 ng/mL vs. 3.45 +/- 2.64 ng/mL, respectively).",
            "output": [
                "Is polycystic ovary syndrome associated with elevated plasma soluble CD40 ligand , a marker of coronary artery disease?"
            ]
        },
        {
            "id": "task847-830493f15cca44ceb1e71b48df6ebe02",
            "input": "Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5-HT) neurons in the raphe nuclei, together with brain growth retardation. The current study tested the hypothesis that concurrent treatment with either an activity-dependent neurotrophic factor (ADNF) agonist peptide [SALLRSIPA, (SAL)] or an activity-dependent neurotrophic protein (ADNP) agonist peptide [NAPVSIPQ, (NAP)] would protect against these alcohol-induced deficits in brain development.', 'Timed-pregnant B6 dams consumed alcohol from embryonic day 7 (E7, before the onset of neurulation) until E15. Fetuses were obtained on E15 and brain sections processed for 5-HT immunocytochemistry, for evaluation of morphologic development of the brainstem raphe and its 5-HT neurons. Additional groups were treated either with SAL or NAP daily from E7 to E15 to assess the potential protective effects of these peptides. Measures of incomplete occlusion of the ventral canal and the frequency and extent of the openings in the rhombencephalon were obtained to assess fetal dysraphia. Counts of 5-HT-immunostained neurons were also obtained in the rostral and caudal raphe.', 'Prenatal alcohol exposure resulted in abnormal openings along the midline and delayed closure of ventral canal in the brainstem. This dysraphia was associated with reductions in the number of 5-HT neurons both in the rostral raphe nuclei (that gives rise to ascending 5-HT projections) and in the caudal raphe (that gives rise to the descending 5-HT projections). Concurrent treatment of the alcohol-consuming dams with SAL prevented dysraphia and protected against the alcohol-induced reductions in 5-HT neurons in both the rostral and caudal raphe. NAP was less effective in protecting against dysraphia and did not protect against 5-HT loss in the rostral raphe, but did protect against loss in the caudal raphe.",
            "output": [
                "Do peptidergic agonists of activity-dependent neurotrophic factor protect against prenatal alcohol-induced neural tube defects and serotonin neuron loss?"
            ]
        },
        {
            "id": "task847-ce423b4ae08f4085b0778d94e76f2033",
            "input": "To identify a biomarker of ovarian cancer response to chemotherapy. PATIENTS AND METHODS Study: participants had epithelial ovarian cancer treated with surgery followed by platinum-based chemotherapy. DNA and RNA were isolated from frozen tumors and normal DNA was isolated from matched peripheral blood. A whole-genome loss of heterozygosity (LOH) analysis was performed using a high-density oligonucleotide array. Candidate genomic areas that predicted enhanced response to chemotherapy were identified with Cox proportional hazards methods. Gene expression analyses were performed through microarray experiments. Candidate genes were tested for independent effects on survival using Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test.', 'Using a whole-genome approach to study the molecular determinants of ovarian cancer response to platinum-based chemotherapy, we identified LOH of a 13q region to predict prolonged progression-free survival (PFS; hazard ratio, 0.23; P = .006). ERCC5 was identified as a candidate gene in this region because of its known function in the nucleotide excision repair pathway, the unique DNA repair pathway that removes platinum-DNA adducts. We found LOH of the ERCC5 gene locus and downregulation of ERCC5 gene expression to predict prolonged PFS. Integration of genomic and gene expression data shows a correlation between 13q LOH and ERCC5 gene downregulation.",
            "output": [
                "Is eRCC5 a novel biomarker of ovarian cancer prognosis?"
            ]
        },
        {
            "id": "task847-1ccf5ebf2b13434aa1cc8aabf6226777",
            "input": "Corticosteroids are a critical component of therapy for acute lymphoblastic leukemia (ALL) but are associated with late effects, such as osteoporosis. Risk factors remain poorly defined. Because CRHR1 polymorphisms have been associated with other corticosteroid effects, our goal was to define whether CRHR1 polymorphisms predict which patients with ALL are likely to develop bone mineral deficits.', 'The mean bone mineral density z scores of 309 long-term survivors of ALL were determined by quantitative computed tomography of the trabecular lumbar spine. We analyzed whether CRHR1 genotypes, adjusted for sex, ALL treatment regimen, and weight, could predict bone density.', 'We found that three single nucleotide polymorphisms (SNPs), all in linkage disequilibrium, were associated with bone density in a sex-specific manner. Bone density was lower in males (P = .001), in nonblack patients (P < .08), in those who were not overweight (P < .001), and in those who received intensive antimetabolites and glucocorticoids (P < .001). After adjustment for these features, the G allele at the rs1876828 SNP was associated with lower z scores (P = .02) in males but tended to have the opposite association in females (P = .09).",
            "output": [
                "Do cRHR1 polymorphisms predict bone density in survivors of acute lymphoblastic leukemia?"
            ]
        },
        {
            "id": "task847-fd757cad51bf4960bcef3b1ffb896ba0",
            "input": "In recent years, the concept of prosthodontic-driven implantology has received more attention. The precise placement of implants in accordance with greater safety and confidence allow the practitioner to offer a safer, more secure and predictable treatment than could previously be provided. In this report, this novel approach is illustrated through description of 1 difficult case.', 'Using principles of computer-assisted design and rapid manufacturing, the data acquisitioned from computerized tomography was used to plan implant rehabilitation and to transfer this information to the surgery as well.', 'The procedure of implant planning in this sophisticated technique has potential to yield substantial public health benefits.",
            "output": [
                "Do a novel stereolithographic surgical guide template for planning treatment involving a mandibular dental implant?"
            ]
        },
        {
            "id": "task847-af7e6c963ef24e5aa0ddd64d90144919",
            "input": "We investigated whether neural stem cells (NSC) with transgenic expression of human nerve growth factor (hNGF) transplanted into the brain could offer a therapeutic option for the treatment of Alzheimer's disease (AD).\", 'We infused okadaic acid into rat lateral ventricles to establish a chronic AD animal model. In addition, NSC were stably transduced with hNGF and enhanced green fluorescent protein (eGFP) genes (NSC-hNGF-eGFP) by using a recombination adeno-associated virus serotype 2 (rAAV2) vector. These genetically modified stem cells were grafted into the cerebral cortex of AD rats.', 'AD model rats showed significant damage in learning and memory function, with the formation of senile plaques and neurofibrillary tangles in the cerebral cortex. The transferred hNGF gene conferred stable and high levels of protein expression in NSC in vitro. Moreover, the NSC-hNGF-eGFP, but not the NSC, survived, integrating into the host brain and enhancing cognitive performance after transplantation.",
            "output": [
                "Do neural stem cells improve learning and memory in rats with Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-1ad38c3ba5724075a88881c3d59fa887",
            "input": "The expression of tight junction-related transmembrane protein claudin-7 (CLDN7) and its regulatory mechanism were investigated in colorectal carcinomas (CRCs).', \"Methylation-specific polymerase chain reaction and treatment with the demethylating agent 5-aza-2'-deoxycytidine were conducted to analyze the methylation status at the CLDN7 promoter region in the Colo320 CRC cell line. We used a total of 26 stage 0 CRCs with an adenoma component and 90 invasive CRCs (stage I-IV), as well as their corresponding lymph node metastases, in an immunohistochemical study.\", \"In Colo320 (CLDN7-negative) cells, hypermethylation at the CLDN7 promoter was detected and treatment with 5-aza-2'-deoxycytidine restored CLDN7 expression. In CRC tissues, decreased CLDN7 expression was detected in 62% of stage 0 CRCs and 80% of stage I-IV CRCs, compared with their adjacent adenoma lesions and nonneoplastic epithelia, which had a close correlation with the incidence of vessel infiltration and clinicopathologic stage. Hypermethylation at the CLDN7 promoter was detected in 20% of CRCs with low CLDN7 expression. However, CLDN7 expression tended to be re-expressed in their corresponding lymph node metastases.",
            "output": [
                "Does hypermethylation-modulated downregulation of claudin-7 expression promote the progression of colorectal carcinoma?"
            ]
        },
        {
            "id": "task847-e60582523b244e81b9bcf13d065efaf2",
            "input": "Gene therapy for severe von Willebrand disease (vWD) seems an interesting treatment alternative with long-term therapeutic potential. We investigated the feasibility of targeting the liver for ectopic expression of physiologically active von Willebrand factor (vWF).', 'The capacity of transgene-encoded murine vWF to restore vWF function was studied in a mouse model of severe vWD after liver-specific gene transfer by hydrodynamic injection. By using a hepatocyte-specific alpha1 antitrypsin promoter, a considerably higher and longer-lasting vWF expression was obtained when compared with a cytomegalovirus promoter, reaching maximum vWF plasma levels that are 10+/-1 times higher than the wild-type level. Liver-expressed vWF showed the full range of multimers, including the high molecular weight multimers, and restored factor VIII plasma levels, consistent with correction of the bleeding time 3 but not 7 days after gene transfer. Importantly, transgene encoded plasma vWF restored proper platelet adhesion and aggregation in a FeCl(3) induced thrombosis model.",
            "output": [
                "Is restoration of plasma von Willebrand factor deficiency sufficient to correct thrombus formation after gene therapy for severe von Willebrand disease?"
            ]
        },
        {
            "id": "task847-971b67d858554417aa2333366b1b5367",
            "input": "Insulin resistant states are associated with increased fatty acid flux to liver and intestine, which stimulates the production of triglyceride-rich lipoproteins (TRL). ApoC-III production and plasma and TRL concentrations are increased in insulin resistance and may contribute to the hypertriglyceridemia of these conditions. The mechanism underlying that increase is not known, but because apoC-III and VLDL production are closely linked we hypothesized that FFAs may stimulate TRL apoC-III production.', 'We used Intralipid/heparin (IH) to raise plasma FFA in 12 healthy men in the fed state, and stable isotopes to examine apoC-III metabolism. TRL apoC-III concentration was significantly higher in the IH study, and this increase was associated with higher production (PR) and fractional catabolic rate (FCR). The increase in production was greater than in FCR (90% versus 30%, respectively), accounting for the elevated concentration. Glycerol infusion had no effect on apoC-III concentration, PR, or FCR compared to saline, indicating that the effect was not attributable to glycerol released from intralipid.",
            "output": [
                "Is triglyceride-rich lipoprotein-associated apolipoprotein C-III production stimulated by plasma free fatty acids in humans?"
            ]
        },
        {
            "id": "task847-163e9f992bdc4d34afc32ae239dda9d2",
            "input": "Cisplatin (CDDP) is one of the major chemotherapeutic drugs, but tumor cells' acquired resistance to CDDP limits its therapeutic potentials. One of the main reasons of resistance is reduced drug accumulation. The mechanism by which tumor cells accumulate reduced CDDP is not well elucidated yet. The aim of this study was to investigate what regulates intracellular CDDP accumulation.\", 'Six different types of oral squamous carcinoma cells were used in this study. Assessment of CDDP sensitivity was determined by measuring the ATP level of the cells. Intracellular CDDP and copper (Cu) accumulation were measured and CDDP efflux study was conducted. Assessment of Na(+),K(+)-ATPase alpha and beta subunits, ATP7A and ATP7B was done by western blotting. Specific activities of Na(+),K(+)-ATPase and copper-transporting P-type ATPase (Cu(2+)-ATPase) were detected and a role of Na(+),K(+)-ATPase inhibitor in intracellular CDDP accumulation was examined.', 'Among the cells HSC-3 and BHY cells were found most CDDP-sensitive and CDDP-resistant, respectively. The most CDDP-sensitive HSC-3 cells exhibited an increased intracellular cisplatin accumulation, high Na(+),K(+)-ATPase activity and over-expressed Na(+),K(+)-ATPase alpha and beta subunits, ATP7A and ATP7B, compared to the most CDDP-resistant BHY cells, but there were no such differences between the two in the CDDP efflux level or Cu(2+)-ATPase activity. Moreover, pretreatment with Na(+),K(+)-ATPase inhibitor markedly reduced intracellular cisplatin accumulation.",
            "output": [
                "Is cisplatin sensitivity of oral squamous carcinoma cells regulated by Na+ , K+-ATPase activity rather than copper-transporting P-type ATPases , ATP7A and ATP7B?"
            ]
        },
        {
            "id": "task847-57fad43df8a843e9935dcf1124c21c68",
            "input": "Assessing acute myocardial infarction (MI) with respect to long-term survival is not easy. Authorities in the field suggest that inflammation predicts short-range (up to 17 months) coronary death. It is not known whether long-term survival is associated with the inflammatory response. In this study, we evaluate the relationships between survival for more than 8 years and inflammation, i.e., circulating interleukin-6 (IL-6) and neutrophil counts, in acute MI.', 'Patients with ST-segment elevation MIs (STEMI; n=33) and non-ST-segment MIs (non-STEMI; n=39) in 1996 were included in the study. All STEMI patients received thrombolytic therapy. Acute coronary angiography was not an option. Determination of IL-6 and neutrophils was carried out within 24 h after commencement of pain. The subjects were followed for more than 8 years (until December 31, 2005) using the national death registry. Inflammatory markers at the time of MI were compared with long-term survival (n=35).', 'At the time of acute MI, survivors for more than 8 years proved to have lower IL-6 (p<0.01) and decreased neutrophil counts (p<0.05). The differences remained (p<0.01 for both markers) when excluding deaths (n=11) occurring in 1996 and 1997. Subsequently, the subjects were divided into two equally sized groups, depending on their IL-6 values at the beginning of the study. As expected, a lower IL-6 was associated with a more favorable long-term prognosis (p<0.01).",
            "output": [
                "Are interleukin-6 and neutrophils associated with long-term survival after acute myocardial infarction?"
            ]
        },
        {
            "id": "task847-a49141c0cf904e07864443c88b549ab2",
            "input": "The herbicidal mode of action of flamprop-M-methyl [methyl N-benzoyl-N-(3-chloro-4-fluorophenyl)-D-alaninate] was investigated.', 'For initial characterization, a series of bioassays was used, which indicated a mode of action similar to that of mitotic disrupter herbicides. Cytochemical fluorescence studies, which included monoclonal antibodies against polymerized tubulin, were applied to elucidate effects on mitosis and microtubule assembly in maize roots. When seedlings were root treated with 50 microM of flamprop-M-methyl, cell division activity in meristematic root tip cells ceased within 4 h. The compound severely disturbed the orientation of spindle and phragmoblast microtubules, leading to defective spindle and phragmoblast structures. Cortical microtubules were only slightly affected. In late anaphase and early telophase cells, phragmoblast microtubules were disorganized in multiple arrays that hampered regular cell plate deposition in cytokinesis. Microtubules of the spindle apparatus were found attached to chromosomal kinetochores, but did not show regular organization associated with a zone of microtubule-organizing centres at the opposite ends of the cell. On account of this loss of spindle organization, chromosomes remained in a condensed state of prometaphase or metaphase. Unlike known microtubule disrupter herbicides, flamprop-M-methyl and its biologically active metabolite flamprop did not inhibit soybean tubulin polymerization to microtubules in vitro at 50 microM. In contrast, soybean plants responded sensitively to the compounds.",
            "output": [
                "Does the herbicide flamprop-M-methyl have a new antimicrotubule mechanism of action?"
            ]
        },
        {
            "id": "task847-e70b33a6b4e24dd5acff2fab5e283d77",
            "input": "The quality of a child's motor repertoire at age 3 to 4 months postterm is predictive of later cerebral palsy (CP). Its predictive power for minor neurologic dysfunction (MND) is unclear. This study aimed to investigate the predictive value of the quality of the early motor repertoire for the development of MND at school age.\", \"We assessed the motor repertoire from video recordings made at 6 to 24 weeks postterm in 82 preterm infants (mean gestational age, 29.7 +/- 1.9 weeks; mean birth weight, 1183 +/- 302 g). At age 7 to 11 years, Touwen's neurologic examination was performed, and the children were classified as normal (n = 49; 60%), MND (n = 18; 22%), or CP (n = 15; 18%).\", 'Multiple logistic regression analysis showed that the quality of fidgety movements (FMs) and the quality of the concurrent motor repertoire had independent prognostic value for MND at school age. Abnormal FMs evolved into MND in 64% of the children. Nine of the 28 children with normal FMs and an abnormal concurrent motor repertoire developed abnormally (32%). Only 1 child of the 21 children with normal FMs and a normal concurrent motor repertoire developed MND (5%).",
            "output": [
                "Does the quality of the early motor repertoire in preterm infants predict minor neurologic dysfunction at school age?"
            ]
        },
        {
            "id": "task847-c64351669e8f4b59bf59dfaaa1c00cb0",
            "input": "S100A4 is a metastasis-associated protein which has been linked to multiple cellular events, and has been identified extracellularly, in the cytoplasm and in the nucleus of tumor cells; however, the biological implications of subcellular location are unknown. Associations between a variety of posttranslational protein modifications and altered biological functions of proteins are becoming increasingly evident. Identification and characterization of posttranslationally modified S100A4 variants could thus contribute to elucidating the mechanisms for the many cellular functions that have been reported for this protein, and might eventually lead to the identification of novel drugable targets.', 'S100A4 was immuoprecipitated from a panel of in vitro and in vivo sources using a monoclonal antibody and the samples were separated by 2D-PAGE. Gels were analyzed by western blot and silver staining, and subsequently, several of the observed spots were identified as S100A4 by the use of MALDI-TOF and MALDI-TOF/TOF.', 'A characteristic pattern of spots was observed when S100A4 was separated by 2D-PAGE suggesting the presence of at least three charge variants. These charge variants were verified as S100A4 both by western immunoblotting and mass spectrometry, and almost identical patterns were observed in samples from different tissues and subcellular compartments. Interestingly, recombinant S100A4 displayed a similar pattern on 2D-PAGE, but with different quantitative distribution between the observed spots.",
            "output": [
                "Does the metastasis-associated protein S100A4 exist in several charged variants suggesting the presence of posttranslational modifications?"
            ]
        },
        {
            "id": "task847-4674eac30fe74cebb1fe9647f4a9a2bb",
            "input": "Whole-genome physical maps facilitate genome sequencing, sequence assembly, mapping of candidate genes, and the design of targeted genetic markers. An automated protocol was used to construct a Vitis vinifera 'Cabernet Sauvignon' physical map. The quality of the result was addressed with regard to the effect of high heterozygosity on the accuracy of contig assembly. Its usefulness for the genome-wide mapping of genes for disease resistance, which is an important trait for grapevine, was then assessed.\", 'The physical map included 29,727 BAC clones assembled into 1,770 contigs, spanning 715,684 kbp, and corresponding to 1.5-fold the genome size. Map inflation was due to high heterozygosity, which caused either the separation of allelic BACs in two different contigs, or local mis-assembly in contigs containing BACs from the two haplotypes. Genetic markers anchored 395 contigs or 255,476 kbp to chromosomes. The fully automated assembly and anchorage procedures were validated by BAC-by-BAC blast of the end sequences against the grape genome sequence, unveiling 7.3% of chimerical contigs. The distribution across the physical map of candidate genes for non-host and host resistance, and for defence signalling pathways was then studied. NBS-LRR and RLK genes for host resistance were found in 424 contigs, 133 of them (32%) were assigned to chromosomes, on which they are mostly organised in clusters. Non-host and defence signalling genes were found in 99 contigs dispersed without a discernable pattern across the genome.",
            "output": [
                "Does a physical map of the heterozygous grapevine 'Cabernet Sauvignon ' allows map candidate genes for disease resistance?"
            ]
        },
        {
            "id": "task847-1a5a5bf4ec9541b0ba49e7d0b777e7a7",
            "input": "We studied the impact of acute opioid administration on work-related exercise performance in patients with chronic back pain. A double-blinded, random-order, placebo-controlled, crossover trial was conducted. Subjects were predominantly men (63%), with a mean age of 49 years. Subjects performed a continuous lifting and lowering test to voluntary fatigue at a load equivalent to 33% of their predetermined maximal lifting load twice: Once after receiving a single intravenous dose of 1 mug/kg fentanyl (a narcotic analgesic) and once after saline placebo. Of the 30 subjects undergoing testing, 3 subjects were unable to complete testing due to medication-induced nausea. Subjects lifted on average 29.4 +/- 17.9 kg under the influence of fentanyl versus 25.6 +/- 3.1 kg with placebo (effect size = 0.23). Time to fatigue was higher in the fentanyl group (312 +/- 251.4 vs 231 +/- 199.9 seconds, effect size = 0.40), and these subjects also performed more total work (7004 +/- 5144 vs 4748 +/- 3147 J, effect size = 0.72). Opioid analgesia improves lifting performance in the short term in individuals with chronic back pain. Longer trials of the effectiveness of opioid analgesia as an adjunct to functional restoration programs are recommended.",
            "output": [
                "Does acute opioid administration improve work-related exercise performance in patients with chronic back pain?"
            ]
        },
        {
            "id": "task847-93c7fcdd388547ee871fb9da77d9ffa6",
            "input": "To establish the role of FHIT in the pathogenesis hepatocellular carcinoma (HCC).', 'We examined genomic alterations, as well as, mRNA and protein expression patterns from the FHIT gene, in 48 surgically resected hepatocellular carcinoma (HCC) tissues. Additionally, p53 mutations were analyzed.', 'Aberrant FHIT transcripts were detected in 11 of 48 surrounding non-tumor liver tissues and 27 of 48 HCC samples (22.9% vs 56.3%, P = 0.002). No point mutations were identified within the open reading frame region of FHIT. Loss of heterozygosity (LOH) of the FHIT locus was detected in 4 of 42 informative cases for D3S1300, and 3 of 29 informative cases for D3S1313. Reduced expression of FHIT protein (Fhit) was observed in 8 (16.7%) of 48 HCC samples, with complete loss of Fhit in only 1 case. There were no associations with abnormal transcripts, LOH, and Fhit expression. p53 mutations were identified in 9 of the 48 HCC cases. However, none of the cases displayed a G to T transversion at p53 codon 249.",
            "output": [
                "Are fragile histidine triad gene alterations essential for hepatocellular carcinoma development in South Korea?"
            ]
        },
        {
            "id": "task847-2d99f75ffb8f433f8910c6650ca8dce2",
            "input": "Resectable adenocarcinomas in the pancreatic head, by definition \"periampullary\", originate from ampullary, duodenal, biliary, or ductal pancreatic epithelium. Typically, periampullary adenocarcinomas have either intestinal or pancreatobiliary type of differentiation, and the type of differentiation might be prognostically more important than the anatomic site of origin. The aim of the study was to determine whether the histologic type of differentiation is an independent prognostic factor in periampullary adenocarcinoma, and whether tumour origin predicts the prognosis in pancreatobiliary type carcinomas independently of resection margin involvement, tumour size, nodal involvement, perineural and vascular infiltration, and degree of differentiation.', 'Histopathologic variables in 114 consecutively resected periampullary adenocarcinomas of pancreatobiliary (n = 67) and intestinal (n = 47) type differentiation were evaluated using a standardized, systematic protocol for evaluation of the resected specimen (study group). Histologic type of differentiation and tumour origin were compared as predictors of survival, and the results were validated by comparison with a historical control group consisting of 99 consecutive pancreaticoduodenectomies performed before standardization of histopathologic evaluation. Associations between histopathologic variables were evaluated by Chi-square and Mann-Whitney tests. Survival was estimated by the Kaplan-Meier method, comparing curves using log-rank test, and by univariate and multivariable Cox regression analysis.', 'Both in the study group (n = 114) and in the historical control group (n = 99), the histologic type of differentiation independently predicted survival, while tumour origin predicted survival only in univariate analysis. Independent adverse predictors of survival in the study group were pancreatobiliary type differentiation (p < 0.001; HR 3.1; CI 1.8-5.1), regional lymph node involvement (p < 0.001; HR 2.5; CI 1.5-4.4), vessel involvement (p = 0.012; HR 1.9; CI 1.2-3.1), and increasing tumour diameter (measured in cm, p = 0.011; HR 1.3; CI 1.1-1.5). For pancreatobiliary differentiated adenocarcinomas (n = 67), lymph node status, vessel involvement, and tumour diameter remained independent prognostic factors, while tumour origin did not independently predict the prognosis due to significant association with tumour size (p < 0.001) and lymph node involvement (p = 0.004).",
            "output": [
                "Is pancreatobiliary versus intestinal histologic type of differentiation an independent prognostic factor in resected periampullary adenocarcinoma?"
            ]
        },
        {
            "id": "task847-8d02838e491947bbb0a44fb6180b4d6c",
            "input": "Intestinal ischemia-reperfusion (II/R) induced acute lung injury is mediated by activated neutrophils and formation of free radicals. Several antioxidants have been shown to attenuate such remote organ injury. We studied the effects of zinc aspartate on lung injury induced by II/R in rats.', 'Twenty-four Sprague-Dawley rats were randomized into three groups. Group I was the control. Animals in Groups II and III (II/R + zinc aspartate [ZA]) underwent 60 min of ischemia and 60 min of reperfusion, respectively. Rats in Group III also received 50 mg/kg zinc aspartate before 15 min of reperfusion. Lung tissue samples and bronchoalveolar lavage fluid were obtained to assess lung tissue myeloperoxidase (MPO), adenosine deaminase (ADA), xanthine oxidase (XO), glutathione peroxidase (GPx) activities, and nitric oxide (NO), malondialdehyde (MDA) levels. Also, the levels of MDA, NO, and MPO activity were determined in bronchoalveolar lavage fluid.', 'Compared with the control, lung tissue MDA, NO levels, and MPO, ADA, XO activities were markedly increased (P < 0.05), whereas GPx activity significantly decreased in the II/R group (P < 0.05). However, administration of ZA significantly reversed these effects by reducing the levels of MDA, NO, and decreasing MPO, ADA, XO activities (P < 0.05). In addition, ZA significantly increased GPx activity (P < 0.05). The activity of MPO and the levels of NO and MDA were found to be higher in bronchoalveolar lavage fluid in II/R group than the control (P < 0.05). Zinc aspartate significantly diminished MPO activity and the levels of NO and MDA compared with that of control rats (P < 0.05).",
            "output": [
                "Does zinc aspartate alleviate lung injury induced by intestinal ischemia-reperfusion in rats?"
            ]
        },
        {
            "id": "task847-c44d9aa15ecd4f149e10a7e30d731ad0",
            "input": "The molecular mechanism involved in the hypertrophy of the orbital fat in patients with Graves' ophthalmopathy or thyroid eye disease (TED) remains unclear. Comparison of genome-wide expression profiles may help in the search for the gene sets involved in TED.\", 'Twenty-five orbital adipose tissue specimens were obtained, from which the RNA was isolated. Four of the tissue specimens (from four individuals, two with TED and two control subjects) were subjected to cDNA microarray analysis. The data were analyzed by the gene set enrichment analysis (GSEA) to survey the biological pathways involved in the pathogenesis of TED. Messenger RNA levels of some top-ranked genes in GSEA-selected pathways are validated by quantitative PCR (QPCR).', 'The expression of specific gene sets related to lytic vacuoles, lysosomes, and vacuoles were different between the specimens obtained from patients with TED and control subjects (P < 0.001). These three gene sets overlapped. For QPCR, four top-ranked genes were selected from these overlapping gene sets and another one that related to visual failure, using 21 independent samples of patients with TED (n = 15) and control subjects (n = 6). The results showed that ceroid-lipofuscinosis, neuronal 2, late infantile (CLN2; P = 0.044) and ceroid-lipofuscinosis, neuronal 3, juvenile (CLN3, which related to visual failure; P = 0.012) were significantly downregulated in the orbital fat of patients with TED. The expression of the beta subunit of hexosaminidase A (HEXB) was reduced as well, but the change did not reach statistical significance (P = 0.058).",
            "output": [
                "Are lysosome-related genes regulated in the orbital fat of patients with graves ' ophthalmopathy?"
            ]
        },
        {
            "id": "task847-8ff35f4157d94c80847f1d5f63e94a86",
            "input": "To determine the effect of subthalamic stimulation on visually triggered eye and head movements in patients with Parkinson's disease (PD).\", 'We compared the gain and latency of visually triggered eye and head movements in 12 patients bilaterally implanted into the subthalamic nucleus (STN) for severe PD and six age-matched control subjects. Visually triggered movements of eye (head restrained), and of eye and head (head unrestrained) were recorded in the absence of dopaminergic medication. Bilateral stimulation was turned OFF and then turned ON with voltage and contact used in chronic setting. The latency was determined from the beginning of initial horizontal eye movements relative to the target onset, and the gain was defined as the ratio of the amplitude of the initial movement to the amplitude of the target movement.', \"Without stimulation, the initiation of the head movement was significantly delayed in patients and the gain of head movement was reduced. Our patients also presented significantly prolonged latencies and hypometry of visually triggered saccades in the head-fixed condition and of gaze in head-free condition. Bilateral STN stimulation with therapeutic parameters improved performance of orienting gaze, eye and head movements towards the controls' level",
            "output": [
                "Does subthalamic stimulation improve orienting gaze movements in Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-f20965600f6a42969fa5dd2f64f7deed",
            "input": "To determine if oligosaccharides of hyaluronan (o-HA) promotes wound recovery by accelerating angiogenesis and to study the mechanisms by which o-HA stimulates endothelial cell (EC) proliferation.', 'Using hyaluronidase digestion, we prepared a mixture of hyaluronan (HA) fragments sizesd 2 to 10 disaccharides units, and studied their effects on EC growth and migration in mimicking wound recovery in vitro. The effects of o-HA on EC growth in vitro were studied by counting cell numbers. The roles of 2 hyaluronan receptors on EC cells, CD44 and RHAMM (Receptor for HA-Mediated Motility), were studied in initiating signaling cascades, using immunoblot assay. Signal transduction was determined by blocking antibodies to CD44 and RHAMM. An in vitro wound healing model was prepared by scratching the cellular layer of cultured EC, and movement of cells into the denuded area was quantified.', 'o-HA was a strong stimulator to EC proliferation at low concentration 10microg/ml compared with native high molecular weight HA (n-HA) (P < 0.01). Signal transduction may be initiated by o-HA via RHAMM receptor on EC membrane, but not CD44. In the in vitro model, the lesion area was nearly completely recovered when the EC layer was exposed to o-HA 40hrs post-injury, whereas the wound area remained half recovered pretreated with native undegraded large HA and control medium.(P < 0.05 from 24 to 40hrs).",
            "output": [
                "Are hyaluronan oligosaccharides potential stimulators to angiogenesis via RHAMM mediated signal pathway in wound healing?"
            ]
        },
        {
            "id": "task847-a5cb43db08cb45c0a9595cef2e5d35e5",
            "input": "Genomes possess different levels of non-randomness, in particular, an inhomogeneity in their nucleotide composition. Inhomogeneity is manifest from the short-range where neighboring nucleotides influence the choice of base at a site, to the long-range, commonly known as isochores, where a particular base composition can span millions of nucleotides. A separate genomic issue that has yet to be thoroughly elucidated is the role that RNA secondary structure (SS) plays in gene expression.', \"We present novel data and approaches that show that a mid-range inhomogeneity (~30 to 1000 nt) not only exists in mammalian genomes but is also significantly associated with strong RNA SS. A whole-genome bioinformatics investigation of local SS in a set of 11,315 non-redundant human pre-mRNA sequences has been carried out. Four distinct components of these molecules (5'-UTRs, exons, introns and 3'-UTRs) were considered separately, since they differ in overall nucleotide composition, sequence motifs and periodicities. For each pre-mRNA component, the abundance of strong local SS (< -25 kcal/mol) was a factor of two to ten greater than a random expectation model. The randomization process preserves the short-range inhomogeneity of the corresponding natural sequences, thus, eliminating short-range signals as possible contributors to any observed phenomena.",
            "output": [
                "Does genomic mid-range inhomogeneity correlate with an abundance of RNA secondary structures?"
            ]
        },
        {
            "id": "task847-73dc14dca0f444ce8a757029966db56a",
            "input": "Linitis plastica-type gastric carcinoma remains a disease with poor prognosis despite an aggressive surgical approach. Although a prominent pattern of disease failure is peritoneal carcinomatosis, some patients experience rapid disease progression without signs of the peritoneal disease.', 'Clinicopathologic data from 178 patients with linitis plastica-type gastric cancer operated on between 1991 and 2000 were analyzed. Survival stratified by curability of surgery, pN stage, and patterns of failure were evaluated by using the Kaplan-Meier method, and chi(2) test was used to evaluate correlation between the number of metastatic lymph nodes in terms of pN categories and the incidence of various patterns of metastasis and recurrence. Cox regression hazard model was used to identify independent prognostic factors.', 'R0 resection was performed only among 82 patients (46% of those who underwent laparotomy). Node metastasis was frequent with only 22 patients classified as pN0. Peritoneal carcinomatosis was observed in 131 patients and was the commonest pattern of recurrence. Bone metastasis, found in 13 patients, was associated with poor outcome, and its incidence was significantly correlated with the number of metastatic nodes. pT4 status and pN3 status were identified as significant independent prognostic determinants.",
            "output": [
                "Is the number of metastatic lymph nodes a significant risk factor for bone metastasis and poor outcome after surgery for linitis plastica-type gastric carcinoma?"
            ]
        },
        {
            "id": "task847-b776a51a9abd43e989fd80adb4ff8ebb",
            "input": "Congenital cystic adenomatoid malformation (CCAM) of the lung may result from a localized aberrant epithelial-mesenchymal interaction during lung development. We used laser microdissection (LMD) to isolate the epithelium and mesenchyme of CCAM, and studied candidate gene expression in these pure cell populations.', 'Congenital cystic adenomatoid malformation tissue was obtained from fetal (n = 5) and postnatal (n = 5) surgical specimens. Normal fetal lung (n = 10) was obtained from abortus material, and normal postnatal lung (n = 5) was identified from surgical specimens. Whole tissue was analyzed using immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Using LMD, columnar bronchiolar type epithelium and underlying mesenchyme were isolated. Multiplex nested RT-PCR was then used to detect message levels of candidate genes.', 'Reverse transcriptase polymerase chain reaction performed on LMD-isolated tissue, but not whole tissue homogenate, revealed differences between CCAM and normal lung. In this report, we focus on the fibroblast growth factor (FGF) family. By RT-PCR, there was 4-fold more epithelial expression of FGF9 in fetal CCAM vs normal fetal lung (P < .07). This was qualitatively confirmed by immunohistochemistry. We also detected decreased FGF7 expression in CCAM mesenchyme (P < .05) but no significant differences in FGF10 or FGFR2.",
            "output": [
                "Does laser microdissection allow detection of abnormal gene expression in cystic adenomatoid malformation of the lung?"
            ]
        },
        {
            "id": "task847-9d862af4604c475e97cb5e882ddd93c8",
            "input": "The purpose of the study was to measure the effect of splenectomy on packed-cell transfusion requirement in children with sickle cell disease.', \"Thirty-seven sickle cell children who underwent splenectomies between January 2000 and May 2006 at a children's hospital were reviewed. Data were collected 6 months preoperatively to 12 months postsplenectomy. Paired t test, analysis of variance, and multivariable regression analyses were performed.\", 'Of 37 children with median age 11 years (range, 2-18 years), 34 (21 males) had data that allowed analyses. Twenty-six had Hgb-SS, 5 had Hgb-SC, and 3 had Hgb S-Thal. Laparoscopic splenectomy was attempted in 36 and completed successfully in 34 (94% success). The number of units transfused decreased by 38% for 0 to 6 months and by 45% for 6 to 12 months postsplenectomy. Postoperatively, hematocrit levels increased and reticulocytes concurrently decreased with a reduction in transfusion clinic visits. The decrease in transfusion was not influenced by spleen weight, age, or hemoglobin type. Two children had acute chest syndrome (6%), and 1 had severe pneumonia (3%).",
            "output": [
                "Does splenectomy reduce packed red cell transfusion requirement in children with sickle cell disease?"
            ]
        },
        {
            "id": "task847-e562af53ea674b6f84a29568f182a79c",
            "input": "The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model.', 'Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings.', 'All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p < 0.05). Although perfusion in the control tumors changed little from day 0 to day 14 (day 0, 18.1 +/- 9.2 mL/min/100 g; day 4, 15.8 +/- 5.6; day 9, 21.7 +/- 12.2; day 14, 27.7 +/- 34), in the sorafenib group, the mean blood flow was significantly lower at day 4 (5.2 +/- 3.2 mL/min/100 g, 77% decrease), day 9 (6.4 +/- 4.0 mL/min/100 g, 66% decrease), and day 14 (6.3 +/- 5.2 mL/min/100 g, 83% decrease) compared with day 0 (23.8 +/- 11.6 mL/min/100 g) (p < 0.05). Poor correlation was seen between changes in blood flow and tumor volume for days 0-9 (r(2) = 0.34), 4-9 (r(2) = 0.0004), and 9-14 (r(2) = 0.16). However, when comparing day 4 images with days 9 and 14 images, seven of 14 (50%) sorafenib-treated tumors had focal areas of new perfusion that correlated with areas of histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)).",
            "output": [
                "Does perfusion MDCT enable early detection of therapeutic response to antiangiogenic therapy?"
            ]
        },
        {
            "id": "task847-ade636e2643a4e9f8450bd53cfb75002",
            "input": "Little is known about the potentiating effect of propofol on neuromuscular blocking drugs. However, some animal studies indicate a dose-dependent increase of the potency of neuromuscular blocking drugs by propofol. This study compared mivacurium potency after five minutes and after 20 min of total intravenous anesthesia with propofol (TIVA propofol).', 'Twenty-eight patients were randomized into two groups, after approval of the Ethics Committee and written consent. Anesthesia was induced, in all patients, using remifentanil 0.5 microg.kg(-1).min(-1) for two minutes, after which: 3 mg.kg(-1) of propofol was injected; a laryngeal mask airway was inserted; and intermittent, positive pressure ventilation was initiated. Anesthesia was maintained using TIVA propofol (titrated using bispectral index monitoring to 40-45). Neuromuscular monitoring consisted of phonomyography at the adductor pollicis muscle. In Groups 5 min and 20 min, a tetanic stimulation of the ulnar nerve commenced after four minutes and after 19 min of TIVA, respectively, followed by controlled, single twitch stimulation at 1 Hz for one minute. Boli of 60, 30, 30, and 30 microg.kg(-1) mivacurium, respectively, were administered (each drug increment was administered after the effect of the previous dose had caused a stable response), and single twitch stimulation continued at 0.1 Hz. The dose-response curve was determined for both groups; potency was calculated using log-probit analysis. Data were presented as mean (SD) and were compared using two-sided analysis of variance, P < 0.05.', 'Patient characteristics were similar in the two groups. The corresponding ED(50) and ED(95) values were greater, at 76.7 +/- 12.4 microg.kg(-1) and 146.6 +/- 27.6 microg.kg(-1) for Group 5 min, vs 46.7 +/- 12.2 microg.kg(-1) and 101.1 +/- 20.2 microg.kg(-1) for Group 20 min, respectively.",
            "output": [
                "Does total intravenous anesthesia with propofol augment the potency of mivacurium?"
            ]
        },
        {
            "id": "task847-268659eab42a43b3a3b3b306c99046ee",
            "input": "Single-laboratory experience showed that flow cytometric (FCM) assessment of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) is feasible in most patients and gives independent prognostic information. It is, however, not known whether FCM analysis can reliably be standardized for multicentric application.', 'An extensive standardization program was installed in four collaborating laboratories, which study FCM-MRD in children treated with the AIEOP-BFM-ALL 2000 protocol. This included methodological alignment, continuous quality monitoring, as well as personnel education by exchange and performance feed-back.', 'Blinded inter-laboratory tests of list-mode data interpretation concordance (n = 202 blood and bone marrow samples from follow-up during induction of 31 randomly selected patients of a total series of n = 395) showed a very high degree of inter-rater agreement among the four centers despite differences in cytometers and software usage (intraclass correlation coefficient [ICC] 0.979 based on n= 800 single values). Lower concordance was reached with amounts of MRD below 0.1%. Comparing data from sample exchange experiments (n = 42 samples; ICC 0.98) and from independent patient cohorts from the four centers (regarding positive samples per time-point of follow-up as well as risk estimates) concordance was also good.",
            "output": [
                "Is standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia : Multicentric assessment feasible?"
            ]
        },
        {
            "id": "task847-1e21c8ea284b43aaaf120aa3e2281775",
            "input": "This study examines the relationship between the existence of chest wall tenderness evoked by palpation and the absence of ischemic heart disease defined by myocardial perfusion imaging in patients with known or suspected stable angina pectoris.', 'Two hundred seventy-five patients were recruited. Myocardial perfusion imaging was performed on 273 of the subjects. Chest pain was classified according to type by criteria given by the Danish Society of Cardiology and severity by the Canadian Cardiovascular Society. Pectoralis major and pectoralis minor were palpated for tenderness using a standardized procedure.', 'The association between tenderness and myocardial perfusion imaging (normal vs abnormal) produced an odds ratio (OR) of 2.24 (confidence interval, 1.26-3.99; P = .009). The OR was the same magnitude and significance when stratified by sex, age, type of pain, or class. When adjusting simultaneously for sex, age, type of pain, and class, the association between tenderness and myocardial perfusion imaging (normal vs abnormal) was still present (OR = 2.57; confidence interval, 1.342-4.902; P = .004).",
            "output": [
                "Is muscular tenderness in the anterior chest wall in patients with stable angina pectoris associated with normal myocardial perfusion?"
            ]
        },
        {
            "id": "task847-ddfc768f4f7242628d764e337876f5ce",
            "input": "To describe a case in which a fluocinolone acetonide implant was used in a patient with serpiginous choroiditis.', 'Case report.', 'A 57-year-old woman with active serpiginous choroiditis threatening the fovea of her right eye received one intravitreous triamcinolone acetonide injection, leading to immediate disease control. An intravitreous fluocinolone acetonide implant was placed, and resulted in ongoing control of the disease as of her 14 months postoperative follow-up.",
            "output": [
                "Do treatment of serpiginous choroiditis with intravitreous fluocinolone acetonide implant?"
            ]
        },
        {
            "id": "task847-cd39f7033ab24377b5dcb1463683c987",
            "input": "To determine the relation of gray matter (GM) and white matter (WM) brain volumes, and WM lesion load, with clinical outcomes 20 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis (MS).', 'Seventy-three patients were studied a mean of 20 years from first presentation with a clinically isolated syndrome (33 of whom developed relapsing-remitting MS and 11 secondary-progressive MS, with the rest experiencing no further definite neurological events), together with 25 healthy control subjects. GM and WM volumetric measures were obtained from three-dimensional T1-weighted brain magnetic resonance images using Statistical Parametric Mapping 2.', 'Significant GM (p < 0.001) and WM atrophy (p = 0.001) was seen in MS patients compared with control subjects. There was significantly more GM, but not WM atrophy, in secondary-progressive MS versus relapsing-remitting MS (p = 0.003), and relapsing-remitting MS versus clinically isolated syndrome (p < 0.001). GM, but not WM, fraction correlated with expanded disability status scale (r(s) = -0.48; p < 0.001) and MS Functional Composite scores (r(s) = 0.59; p < 0.001). WM lesion load correlated with GM (r(s) = -0.63; p < 0.001), but not with WM fraction. Regression modeling indicated that the GM fraction explained more of the variability in clinical measures than did WM lesion load.",
            "output": [
                "Is gray matter atrophy related to long-term disability in multiple sclerosis?"
            ]
        },
        {
            "id": "task847-35412e0a35ad4baf8c1dc2cda17e7556",
            "input": "To examine whether trichostatin A (TSA), a histone deacetylase inhibitor (HDACI), can induce up-regulation of peroxisome proliferator-activating receptor gamma (PPAR gamma) and to see whether LG100268, a retinoid X receptor (RXR) ligand, can inhibit proliferation of endometriotic cells alone or in synergy with ciglitazone, a PPAR gamma agonist.', 'One endometrial stromal cell line and two endometriotic cell lines used as a model system: Western blot analysis to determine whether TSA can up-regulate PPAR gamma expression, and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) proliferation assay to see whether ciglitazone and LG100268 have any antiproliferative effects individually or jointly.', 'Academic.', 'None.', 'Culture of immortalized endometrial and endometriotic cell lines with TSA, or ciglitazone or LG100268.', 'PPAR gamma protein expression levels in cells treated with or without TSA, and number of viable cells treated with or without ciglitazone, LG100268, or both.', 'The TSA treatment resulted in up-regulation of PPAR gamma expression in all cell lines in a dose-dependent fashion. Both ciglitazone and LG100268 inhibited proliferation in a dose-dependent manner, and the antiproliferative effects appeared to be synergistic. In addition, endometriotic cells were more sensitive than endometrial stromal cells to LG100268 treatment.",
            "output": [
                "Do peroxisome proliferator-activated receptor-gamma and retinoid X receptor agonists synergistically suppress proliferation of immortalized endometrial stromal cells?"
            ]
        },
        {
            "id": "task847-665284763bde4d0290f363e3342f36a8",
            "input": "Plasmablastic lymphoma (PBL) and multiple myeloma (MM) are B cell-derived malignancies that share many morphologic and immunophenotypic traits, making the differential diagnosis particularly complicated. We have recently demonstrated that peroxiredoxin I (PrdxI) is expressed in plasma cells but not in B lymphocytes, suggesting that its expression is development-associated.', 'To analyze PrdxI expression in PBL and in MM in order to study its utilization as an additional diagnostic molecular tool.', 'Eight cases of PBL and nine of MM were studied by immunohistochemistry. We have demonstrated that PrdxI expression is closely connected with the immunoglobulin production capacity of the cells, which means high in MM, but absent in PBL cases, except one, wherein few cells were stained.",
            "output": [
                "Is peroxiredoxin I differentially expressed in multiple myelomas and in plasmablastic lymphomas?"
            ]
        },
        {
            "id": "task847-3608ee18ec274f5fae750e47bc14886f",
            "input": "Serum ghrelin levels are elevated in uremic patients. However, no data are available on the relationship between metabolic syndrome and serum ghrelin levels in peritoneal dialysis (PD) patients.', 'Metabolic syndrome and its components were defined using diagnostic criteria recommended by the International Diabetes Federation. Fasting serum samples were taken from 30 PD patients. Serum ghrelin levels were measured by using a commercial enzyme-linked immunosorbent assay kit.', 'Of the 30 PD patients, 53.3% (16/30) had metabolic syndrome. Fasting serum ghrelin corrected inversely with metabolic syndrome among these PDs patients (p = 0.002). By odds ratio (OR) analysis of metabolic syndrome and metabolic syndrome diagnostic criteria, the predictors for metabolic syndrome are fasting glucose [OR: 39.00; 95% confidence interval (CI): 3.80 to 399.85; p < 0.001], triglycerides (OR: 37.50; 95% CI: 3.64 to 386.51; p < 0.001), and waist circumference (OR: 4.20; 95% CI: 1.95 to 9.03; p < 0.001). Univariate linear regression analysis showed that body weight (r = -0.461, p = 0.010), waist circumference (r = -0.390, p = 0.033), and body mass index (r = -0.438, p = 0.016) were negatively correlated with serum ghrelin, and serum high density lipoprotein [HDL (r = 0.626, p < 0.001)] was positively correlated with serum ghrelin. Multivariate forward stepwise linear regression analysis of the significant variables showed that HDL (R(2) change = 0.392; p < 0.001) was the independent predictor of serum ghrelin in PD patients and explained 39.2% of the variance.",
            "output": [
                "Is fasting serum ghrelin level associated with metabolic syndrome in peritoneal dialysis patients?"
            ]
        },
        {
            "id": "task847-fe70efd702454688bd80f8fb19426fad",
            "input": "To evaluate electrophysiologically the auditory nerve and the auditory brainstem function of patients with tinnitus and normal-hearing thresholds using the auditory brainstem response (ABR).', 'Case-control study.', 'Ambulatory section of the Department of Otolaryngology, Hospital de Base de Bras\u00edlia.', 'Thirty-seven individuals with tinnitus and 38 without tinnitus, with ages ranging from 20 to 45 years and pure-tone thresholds of 25 dB or better at frequencies between 500 and 8000 Hz.', 'We compared the latencies of waves I, III, and V; the interpeak intervals I-III, III-V, and I-V; the interaural latency difference (wave V); and the V/I amplitude ratio between the 2 groups.', 'Among the 37 patients in the study group, abnormal results were found in 16 (43%) in at least 1 of the 8 parameters evaluated. When we analyzed the latencies, although the values were on average in the normal range used in the present study, the tinnitus group presented a significant prolongation of the latencies of waves I, III, and V when compared with the control group. Furthermore, we found the interpeak I-III, III-V, and I-V values to be within the normal limits, but the interpeak III-V value was significantly (P = .003) enlarged in the study group compared with the control group. The V/I amplitude ratio found in the tinnitus group was within normal limits; however, a significant (P = .004) difference was found when the 2 groups were compared. The averages of the interaural latency difference (wave V) did not show significant differences in relation to the control group.",
            "output": [
                "Does comparison of auditory brainstem response result in normal-hearing patients with and without tinnitus?"
            ]
        },
        {
            "id": "task847-05b301fa41314af88b1d34a371522d4c",
            "input": "The aim of the present study was to investigate to what extent personality and choice of coping predicted self-reported quality of life (QoL) in successfully treated head and neck squamous cell carcinoma (HNSCC) patients.', 'We determined QoL by the European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC-QLQ) C30/H&N35, personality by the Eysenck Personality Inventory and coping by the COPE questionnaire. All patients younger than 80 years who had been diagnosed with HNSCC in Western Norway in the period from 1992 to1997, and who had survived until 1999, were sampled. Ninety-six patients (90% response rate) were included 48+/-2 months after diagnosis. Fifty-five of 58 eligible patients were interviewed a second time 47+/-1 months after the first interview where neuroticism and QoL questionnaires were answered.', 'Numerical T stage was inversely associated with the second QoL scores (CV: 10-24%). High neuroticism generally predicted low secondary QoL scores both directly (common variance: 17-25%) and adjusted by the QoL values measured simultaneously as the neuroticism (CV: 11-25%). Avoidance focused, problem focused, drinking to cope and coping by humor all predicted QoL scores (CV: 8.5-15%). The present association pattern could still be shown when adjusted for gender, age and educational level when studied by multiple regression analyses.",
            "output": [
                "Do personality and choice of coping predict quality of life in head and neck cancer patients during follow-up?"
            ]
        },
        {
            "id": "task847-9fb05482229c49dc810741aa92120f22",
            "input": "Acute rejection is the major risk factor for the development of subsequent chronic allograft nephropathy (CAN), which is the primary reason for late allograft loss in kidney transplantation. Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) are the main mitogens mediating mesenchymal cell proliferation. Their early post-transplant induction may start cascades leading to the development of CAN. An immunosuppressive drug, FK778, inhibits de novo pyrimidine biosynthesis and several receptor tyrosine kinases (RTKs). Here we investigated its effects on acute and chronic rejection as well as post-transplant PDGF and TGF-beta expression in combination therapy with calcineurin inhibitors (CNIs).', 'Kidney transplantations were performed from DA to WF rats. Syngenic DA-DA grafts were used as controls. Allografts were immunosuppressed with a combination of FK778 (10 mg/kg/day p.o.) and CsA (1.5 mg/kg/day s.c.) or tacrolimus (Tac) (1.5 mg/kg/day p.o.). Grafts were harvested 5 and 90 days after transplantation for histology and immunohistochemistry (PDGF-A, PDGF-B, PDGFR-alpha, PDGFR-beta, TGF-beta, TGF-betaR). The dose response of FK778 on acute rejection was studied with monotherapy of 5, 10 and 20 mg/kg/day. Chronic changes were scored according to the Chronic Allograft Damage Index (CADI).', 'FK778 ameliorated the early post-transplant inflammatory response dose dependently. Additive effects were seen with FK778 and CNIs. Significantly lower CADI scores were seen in combination therapy of FK778 and CNIs compared with CNI monotherapies. FK778 also significantly reduced both early and late PDGF and TGF-beta expression when combined with CNIs.",
            "output": [
                "Does fK778 ameliorate post-transplant expression of fibrogenic growth factors and development of chronic rejection changes in rat kidney allografts?"
            ]
        },
        {
            "id": "task847-452ff90de2b841d5839d4722f9582231",
            "input": "Severe malaria (SM) is classically associated with Plasmodium falciparum infection. Little information is available on the contribution of P. vivax to severe disease. There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths. A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species.', 'This was a prospective cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project. All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking, clinical examination, and laboratory assessment. Case definition of SM was based on the World Health Organization (WHO) criteria adapted for the setting (i.e., clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits, or coma, or respiratory distress, or anaemia [haemoglobin < 5 g/dl]). Out of 17,201 presumptive malaria cases, 9,537 (55%) had a confirmed Plasmodium parasitaemia. Among those, 6.2% (95% confidence interval [CI] 5.7%-6.8%) fulfilled the case definition of SM, most of them in children <5 y. In this age group, the proportion of SM was 11.7% (10.4%-13.2%) for P. falciparum, 8.8% (7.1%-10.7%) for P. vivax, and 17.3% (11.7%-24.2%) for mixed P. falciparum and P. vivax infections. P. vivax SM presented more often with respiratory distress than did P. falciparum (60% versus 41%, p = 0.002), but less often with anaemia (19% versus 41%, p = 0.0001).",
            "output": [
                "Are plasmodium vivax and mixed infections associated with severe malaria in children : a prospective cohort study from Papua New Guinea?"
            ]
        },
        {
            "id": "task847-e09da372e52f4ff399ae4858d67c8854",
            "input": "An endocannabinoid signaling system has not been identified in hamsters.', 'We examined the existence of an endocannabinoid signaling system in Syrian hamsters using neuroanatomical, biochemical, and behavioral pharmacological approaches.', 'The distribution of cannabinoid receptors was mapped, and membrane fatty-acid amide hydrolase (FAAH) activity and levels of fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test, and models of unconditioned and conditioned social defeat.', 'A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain using [3H]CP55,940 binding and autoradiography. The FAAH inhibitor URB597 inhibited FAAH activity (IC50 = 12.8 nM) and elevated levels of fatty-acid amides (N-palmitoyl ethanolamine and N-oleoyl ethanolamine) in hamster brain. Anandamide levels were not reliably altered. The cannabinoid agonist WIN55,212-2 (1- 10 mg/kg i.p.) induced CB1-mediated motor ataxia. Blockade of CB1 with rimonabant (5 mg/kg i.p.) induced anxiogenic-like behavior in the elevated plus maze. URB597 (0.1-0.3 mg/kg i.p.) induced CB1-mediated anxiolytic-like effects in the elevated plus maze, similar to the benzodiazepine diazepam (2 mg/kg i.p.). Diazepam (2-6 mg/kg i.p.) suppressed the expression, but not the acquisition, of conditioned defeat. By contrast, neither URB597 (0.3-3.0 mg/kg i.p.) nor rimonabant (5 mg/kg i.p.) altered unconditioned or conditioned social defeat or rota-rod performance.",
            "output": [
                "Does an endocannabinoid signaling system modulate anxiety-like behavior in male Syrian hamsters?"
            ]
        },
        {
            "id": "task847-213662277286468499cbd77448e67c01",
            "input": "We analyzed in patients with essential tremor (ET) the Thr105Ile polymorphism of the Histamine N-methyltransferase (HNMT) enzyme that is associated to Parkinson's disease (PD) risk.\", 'Leukocytary DNA from 204 ET patients and a control group of 295 unrelated healthy individuals was studied for the nonsynonymous HNMT Thr105Ile polymorphism by using amplification-restriction analyses.', 'Patients with ET showed a higher frequency of homozygous HNMT 105Thr genotypes leading to high metabolic activity (p < 0.015) with a statistically significant gene-dose effect, as compared to healthy subjects. These findings were independent of gender, and of tremor localization, but the association of the HNMT polymorphism is more prominent among patients with late-onset ET (p < 0.007).",
            "output": [
                "Is the nonsynonymous Thr105Ile polymorphism of the histamine N-methyltransferase associated to the risk of developing essential tremor?"
            ]
        },
        {
            "id": "task847-78c00c3cb6864838996c9c52a6f1f833",
            "input": "Mucus hypersecretion is a hallmark of nasal polyposis (NP). Corticosteroids (CS) are first-line treatment for NP, decreasing their size and inflammatory component. However, their effect on mucin production is not well-understood. The aim of this (pilot) study was to investigate CS effect on mucin expression in NP.', 'Patients were randomized in control (n = 9) and treatment (oral prednisone for 2 weeks and intranasal budesonide for 12 weeks; n = 23) groups. Nasal polyposis from nonasthmatic (NP; n = 13), aspirin-tolerant (NP-ATA; n = 11) and aspirin-intolerant (NP-AIA; n = 8) asthmatics were studied. Nasal polyposis biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of CS treatment. Secreted (MUC5AC, MUC5B and MUC8) and membrane-tethered (MUC1, MUC4) mucins (immunohistochemistry) and goblet cells (Alcian blue-periodic acid Schiff) were quantified in both epithelium and glands. Rhinorrea and nasal obstruction were also assessed.', \"At w2, steroids increased MUC1 (from 70 to 97.5) and MUC4 (from 80 to 100) in NP-ATA patients' epithelium compared with baseline (w0). At w12, steroids decreased MUC5AC (from 40 to 5) and MUC5B (from 45 to 2.5) in NP-ATA patients' epithelium and glands, respectively, compared with baseline. No mucin presented significant changes in NP-AIA patients. MUC5AC and MUC5B expression correlated with goblet and mucous cell numbers, respectively, and MUC5AC also with rhinorrea score.",
            "output": [
                "Does corticosteroid therapy increase membrane-tethered while decreases secreted mucin expression in nasal polyps?"
            ]
        },
        {
            "id": "task847-43a36fe4a0e14ac8a77552e9a3cb2215",
            "input": "Mast cells play a central role in allergic and inflammatory diseases. Several reports indicated role of peroxisome proliferator-activated receptor gamma (PPARgamma) on mast cell function. However, there is no report about the role of PPARgamma on differentiation of mast cells from the progenitors. In this study, we investigated the role of PPARgamma in regulating bone marrow-derived mast cell maturation and the therapeutic implications for mast cell-related diseases such as atopic or contact dermatitis.', 'We used in vitro cell culture system for mast cell differentiation from bone marrow-progenitors using specific ligands and lentiviral-mediated short hairpin RNA of PPARgamma, and in vivo murine dermatitis models.', 'Activation of PPARgamma inhibited the maturation of bone marrow progenitors into connective tissue-type mast cells (CTMCs) through up-regulation of GATA-4 and GATA-6 resulting in a decrease in expression of histidine decarboxylase and mast cell histamine content. In comparison, the differentiation of bone marrow progenitors into CTMCs was significantly accelerated by the knockdown of PPARgamma expression by lentiviral-mediated short hairpin RNA. Peroxisome proliferator-activated receptor gamma ligand administration to mice inhibited the maturation of mast cells resulting in attenuation of atopic and contact dermatitis via diminishment of the number of mature mast cells.",
            "output": [
                "Does activation of peroxisome proliferator-activated receptor gamma suppress mast cell maturation involved in allergic diseases?"
            ]
        },
        {
            "id": "task847-b1b9d7d198564cf4ad57d4213847f12a",
            "input": "The purpose of this study was to evaluate patient-specific outcomes and satisfaction using dental implants in a population affected with ectodermal dysplasia.', 'Patient-based data were collected using a self-reported survey instrument sent to patients belonging to a private patient foundation and/or treated previously at a government clinic. A standardized survey instrument was developed to evaluate patient satisfaction, outcomes, and potential complications using dental implants.', 'The survey instrument was mailed to 253 affected individuals self-reported to have various forms of ectodermal dysplasia and who were voluntarily participants in the National Foundation for Ectodermal Dysplasias and/or were participants in the US National Institute for Dental Craniofacial Research Intramural Ectodermal Dysplasia clinical research program. A total of 109 responses were obtained (43% response rate). The duration following completion of implant therapy ranged from to 1 to 23 years. Of the 109 participants, 50% reported either an implant or prosthetic complication with implant treatment, and 24% reported some form of failure with implant therapy. However, 91% of participants reported being either satisfied or very satisfied with dental implants, and 95% reported that the treatment was worth the time and cost.",
            "output": [
                "Do perceptions of outcomes of implant therapy in patients with ectodermal dysplasia syndromes?"
            ]
        },
        {
            "id": "task847-ed38ae442a0741b4844b5d5aef3260f7",
            "input": "The present study explored the effect of dietary oils on lipid composition, antioxidant status, and the activity of the main steroidogenic enzymes in the testis.', 'Forty Wistar rats were randomly assigned to one of four groups (n = 10) fed for 60 d on the same basal diet plus different lipid sources as commercial oils: soybean, olive, coconut, or grapeseed. After sacrifice, testicular lipids and fatty acid composition, free radical biomarkers, antioxidant levels, hormones, and steroidogenic enzymes were determined.', 'The lipid composition of diets produced significant changes in neutral/phospholipids, free/esterified cholesterol, and plasmalogen proportion. Fatty acid patterns of these lipids were also strongly modified, influencing the double bond index. We also found a close correlation between the type of diet and the generation of free radicals. The oxidative stress in testes was higher with the grapeseed oil-supplemented diet and decreased with the other diets in this order: soybean oil > olive oil > coconut oil. Animals fed with the olive oil and coconut oil diets showed the highest testicular levels of antioxidants in addition to significantly high levels of testosterone and 3beta- or 17beta-hydroxysteroid dehydrogenase enzymes.",
            "output": [
                "Do dietary lipids modify redox homeostasis and steroidogenic status in rat testis?"
            ]
        },
        {
            "id": "task847-0f8b9739b7a74332818c233ab241ee87",
            "input": "This study was designed to determine whether novel cardiovascular disease (CVD) risk factors explain the high prevalence of peripheral arterial disease (PAD) among African Americans.', 'Compared with Caucasians, African Americans have higher prevalence of PAD, an association that is not explained by traditional CVD risk factors. The degree to which novel CVD risk markers may explain the higher prevalence is uncertain.', 'A nested case-control study within the San Diego Population Study was performed. The study evaluated 104 persons with PAD and 164 age- and gender-matched control subjects who were employees of a large public university and participated in a peripheral artery and venous disease study. Nine novel CVD risk factors (homocysteine, lipoprotein (a), C-reactive protein, fibrinogen, tumor necrosis factor-alpha, von Willebrand factor, prothrombin fragment 1-2, D-dimer, and plasmin antiplasmin) were measured. Multivariable logistic regression evaluated whether these novel factors attenuated the association of African-American race and PAD and whether there was differential ethnic susceptibility to the novel factors.', 'African Americans had 3-fold higher odds of PAD in age- and gender-matched models (odds ratio [OR] 3.1; 95% confidence interval [CI] 1.5 to 6.4; p < 0.01), an association that was modestly attenuated by adjustment for traditional (OR 2.4; 95% CI 0.9 to 6.1; p = 0.06) and novel CVD risk markers (OR 1.9; 95% CI 0.7 to 4.7; p = 0.18). Among the novel factors, the attenuation was primarily due to fibrinogen and lipoprotein (a). No interactions by novel CVD risk markers (both p values for interaction > or =0.24) were observed.",
            "output": [
                "Do novel cardiovascular risk factors completely explain the higher prevalence of peripheral arterial disease among African Americans . The San Diego Population Study?"
            ]
        },
        {
            "id": "task847-d11847118df7409b89cce96b8af22320",
            "input": "Pichia stipitis xylose reductase (Ps-XR) has been used to design Saccharomyces cerevisiae strains that are able to ferment xylose. One example is the industrial S. cerevisiae xylose-consuming strain TMB3400, which was constructed by expression of P. stipitis xylose reductase and xylitol dehydrogenase and overexpression of endogenous xylulose kinase in the industrial S. cerevisiae strain USM21.', 'In this study, we demonstrate that strain TMB3400 not only converts xylose, but also displays higher tolerance to lignocellulosic hydrolysate during anaerobic batch fermentation as well as 3 times higher in vitro HMF and furfural reduction activity than the control strain USM21. Using laboratory strains producing various levels of Ps-XR, we confirm that Ps-XR is able to reduce HMF both in vitro and in vivo. Ps-XR overexpression increases the in vivo HMF conversion rate by approximately 20%, thereby improving yeast tolerance towards HMF. Further purification of Ps-XR shows that HMF is a substrate inhibitor of the enzyme.",
            "output": [
                "Does pichia stipitis xylose reductase help detoxifying lignocellulosic hydrolysate by reducing 5-hydroxymethyl-furfural ( HMF )?"
            ]
        },
        {
            "id": "task847-6e1fb762dd4e45d0978b0079b9485c9e",
            "input": "Alterations in gene splicing occur in human sporadic colorectal cancer (CRC) and may contribute to tumour progression. The K-ras proto-oncogene encodes two splice variants, K-ras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in CRC. Past studies have established that splicing of both the K-ras oncogene and proto-oncogene is altered in CRC in favour of K-ras 4B. The present study addressed whether the K-Ras 4A proto-oncoprotein can suppress tumour development in the absence of its oncogenic allele, utilising the ApcMin/+ (Min) mouse that spontaneously develops intestinal tumours that do not harbour K-ras activating mutations, and the K-rastmDelta4A/tmDelta4A mouse that can express the K-ras 4B splice variant only. By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively.', \"The relative levels of expression of the K-ras splice variants in normal small intestine and small intestinal tumours were quantified by real-time RT-qPCR analysis. Inbred (C57BL/6) ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice were generated and the genotypes confirmed by PCR analysis. Survival of stocks was compared by the Mantel-Haenszel test, and tumour number and area compared by Student's t-test in outwardly healthy mice at approximately 106 and 152 days of age. DNA sequencing of codons 12, 13 and 61 was performed to confirm the intestinal tumours did not harbour a K-ras activating mutation.\", 'The K-ras 4A transcript accounted for about 50% of K-ras expressed in the small intestine of both wild-type and Min mice. Tumours in the small intestine of Min mice showed increased levels of K-ras 4B transcript expression, but no appreciable change in K-ras 4A transcript levels. No K-ras activating mutations were detected in 27 intestinal tumours derived from Min and compound mutant Min mice. K-Ras 4A deficiency did not affect mouse survival, or tumour number, size or histopathology.",
            "output": [
                "Does the pro-apoptotic K-Ras 4A proto-oncoprotein affect tumorigenesis in the ApcMin/+ mouse small intestine?"
            ]
        },
        {
            "id": "task847-c51414cb0df142afb159fd5c75843fac",
            "input": "Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking.', 'A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001-2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up.', 'Smoking (OR 2.53, 95% CI 1.23-5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46-8.93) were found to be independently associated with relapse of tuberculosis.",
            "output": [
                "Does smoking increase the risk of relapse after successful tuberculosis treatment?"
            ]
        },
        {
            "id": "task847-6349fe6ad14c42f4b01a78c11d22ba33",
            "input": "Mycophenolic acid (MPA) is glucuronidated primarily by uridine diphosphate glucuronosyltransferase enzymes (UGT) 1A9 and 1A8. These enzymes are highly polymorphic resulting in low activity and high expression phenotypes. We hypothesized that polymorphisms of UGT1A9 and 1A8 may alter MPA pharmacokinetics in kidney transplantation.', \"One hundred seventeen kidney (n = 93), pancreas (n = 11), or simultaneous kidney and pancreas (SPK) (n = 13) transplant recipients were studied for the effect of UGT1A9 and UGT1A8 polymorphisms on MPA dose-corrected trough concentrations. Individuals were genotyped for UGT1A8 and UGT1A9 polymorphisms (1A8*2, 1A8*3, 1A9*3, 1A9-275 and 1A9-2152). Linear regression was used to estimate the effect of UGT polymorphisms on the individual's mean MPA dose-corrected trough concentration with and without stratification by calcineurin inhibitor. A multiple linear regression analysis was performed to assess the dependence between the average MPA dose-corrected trough concentration and age, gender, UGT genotype (1A8*2, 1A8*3, 1A9*3, 1A9-275, 1A9-2152), serum albumin, hemoglobin (Hgb), hematocrit (HCT), liver transaminases (AST, ALT), serum creatinine, and bilirubin.\", 'Mycophenolic acid dose-corrected trough concentrations were 60% higher in subjects heterozygous or homozygous for UGT1A8*2 than in those with the wild type (p = 0.02); however, this effect was dependent on concomitant calcineurin inhibitor. When subjects were stratified by calcineurin inhibitor status, the UGT1A8*2 effect was only apparent in the tacrolimus group (p < 0.01). Mycophenolic acid dose-corrected trough concentrations were 70% lower in carriers of the UGT1A9 -275T>A/-2152 C>T polymorphism who received cyclosporine (p < 0.01). There was no effect of the UGT1A9 -275T>A/-2152C>T polymorphism in the tacrolimus group.",
            "output": [
                "Is pharmacogenetic effect of the UGT polymorphisms on mycophenolate modified by calcineurin inhibitors?"
            ]
        },
        {
            "id": "task847-d16c42f417b649dd99e8ab7e77f167ca",
            "input": "Persistent coma is a common finding after cardiac arrest and has profound ethical and economic implications. Evidence suggests that therapeutic hypothermia improves neurological outcome in these patients. In this analysis, we investigate whether therapeutic hypothermia influences the length of intensive care unit (ICU) stay and ventilator time in patients surviving out-of-hospital cardiac arrest.', 'A prospective observational study with historical controls was conducted at our medical ICU. Fifty-two consecutive patients (median age 62.6 years, 43 males, 34 ventricular fibrillation) submitted to therapeutic hypothermia after out-of-hospital cardiac arrest were included. They were compared with a historical cohort (n = 74, median age 63.8 years, 53 males, 43 ventricular fibrillation) treated in the era prior to hypothermia treatment. All patients received the same standard of care. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score. Univariate analyses and multiple regression models were used.', 'In survivors, therapeutic hypothermia and baseline disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] score) were both found to significantly influence ICU stay and ventilator time (all P < 0.01). ICU stay was shorter in survivors receiving therapeutic hypothermia (median 14 days [interquartile range (IQR) 8 to 26] versus 21 days [IQR 15 to 30] in the control group; P = 0.017). ICU length of stay and time on ventilator were prolonged in patients with CPC 3 or 4 compared with patients with CPC 1 or 2 (P = 0.003 and P = 0.034, respectively). Kaplan-Meier analysis showed improved probability for 1-year survival in the hypothermia group compared with the controls (log-rank test P = 0.013).",
            "output": [
                "Does mild therapeutic hypothermia shorten intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls?"
            ]
        },
        {
            "id": "task847-e16515554f9c4656874cc9b6e5446e85",
            "input": "The validity and usefulness of incident reporting and other methods for identifying adverse events remains unclear. This study aimed to compare five methods in general practice.', \"In a prospective observational study, with five general practitioners, five methods were applied and compared. The five methods were physician reported adverse events, pharmacist reported adverse events, patients' experiences of adverse events, assessment of a random sample of medical records, and assessment of all deceased patients.\", 'A total of 68 events were identified using these methods. The patient survey accounted for the highest number of events and the pharmacist reports for the lowest number. No overlap between the methods was detected. The patient survey accounted for the highest number of events and the pharmacist reports for the lowest number.",
            "output": [
                "Is mix of methods needed to identify adverse events in general practice : a prospective observational study?"
            ]
        },
        {
            "id": "task847-37489443abc947e1a9d824dde2aead14",
            "input": "Hypertrophic cardiomyopathy (HCM) is associated with myocardial scarring and ventricular tachycardia (VT). Contrast-enhanced cardiac magnetic resonance imaging (CE-CMR) can quantify myocardial scar, and scar imaging has been documented in patients with HCM. We investigated the assessment of myocardial scar in HCM patients using CE-CMR, and its correlation with proven VT.', 'Twenty-five patients (mean age 54 +/- 8) with HCM who underwent CE-CMR were identified, and clinical data obtained from chart review. Parameters of LV function were calculated from cine imaging, and myocardial scar was assessed using delayed enhancement imaging following gadolinium administration.', 'Myocardial scar was detected in 16 (64%) patients with a mean mass 9 +/- 15 g. Scar was patchy, mid-myocardial and located in the basal anteroseptum, and RV insertion sites. Scar was seen in septal, apical and concentric variants of HCM. Scar mass correlated with both LV Mass (r2 = 0.74) and maximal LV wall thickness (r2 = 0.42). VT occurred in 32% of patients, and was associated with both increased scar mass and wall thickness compared to non-VT patients (21 +/- 22 g vs. 4 +/- 6 g, and 2.4 +/- 0.5 cm vs. 1.8 +/- 0.5 cm, p < 0.05). LV size and function were similar in patients with and without VT. A scar mass of >7 g predicted the presence of VT with a sensitivity of 75% and specificity 82%.",
            "output": [
                "Is myocardial scar detected by contrast-enhanced cardiac magnetic resonance imaging associated with ventricular tachycardia in hypertrophic cardiomyopathy patients?"
            ]
        },
        {
            "id": "task847-e4d338e027e74688ba14da74f7e4f249",
            "input": "The integrity of lipid rafts in cell membranes is important for signal transduction.', 'To determine the distinct effects of beta-glycolipids on the composition of lipid rafts in natural killer T (NKT) cells and on the level of expression of flotillin-2, leukocyte-specific protein tyrosine kinase (Lck), and STAT1-associated pathways.', 'The effects of glycolipids were determined by composition analysis of the raft domains, FACS analysis of the distribution patterns for the raft ganglioside, GM1, and fluorescence microscopy of raft patching. To evaluate the effects of the immune environment on glycolipid-associated alteration of lipid rafts, hepatitis was induced by an intravenous injection of concanavalin A (ConA) in mice treated with various glycolipids.', 'The administration of beta-glucosylceramide, beta-lactosylceramide, and a combination of both significantly altered GM1 content in lymphocyte membranes in an environment-dependent manner. These effects were associated with altered expression levels of flotillin-2, Lck, and STAT1, and with a significant decrease in intrahepatic CD8+ lymphocyte trapping and the alleviation of ConA-induced hepatitis. The administration of alpha-glycolipids failed to induce similar effects.",
            "output": [
                "Is modulation of intracellular machinery by beta-glycolipids associated with alteration of NKT lipid rafts and amelioration of concanavalin-induced hepatitis?"
            ]
        },
        {
            "id": "task847-77a3789b17a440fab2a1f1976088956a",
            "input": "Sleep disordered breathing has been associated with an increased risk for developing coronary heart disease. Data on the effects of sleep disordered breathing on case fatality and prognosis of a myocardial infarction are sparse. The present study aimed to investigate a possible relationship of snoring and case fatality and mortality after an acute myocardial infarction. DESIGN, SETTINGS, PATIENTS, AND MEASUREMENTS: In this study, we enrolled 1660 first acute myocardial infarction cases and examined the effects of self- or relative-reported heavy snoring on case fatality and prognosis. The average follow-up time was 8 years, SD = 262 days.', 'There was a variation in the association between snoring and mortality with time, with a strong association in the first 28 days after infarction but not later during the follow-up. Occasional and regular heavy snorers, when compared to those never having heavy snoring, had a 2.04 (95% confidence interval, 1.50 to 2.79) and 3.30 (95% confidence interval, 2.37 to 4.58) hazard ratio for mortality within the first 28 days after controlling for age, gender, obesity, history of diabetes and hypertension, physical activity, smoking, and education, respectively. There was no association between snoring and new myocardial infarction, stroke, or hospitalization for heart failure during the follow-up.",
            "output": [
                "Is heavy snoring a risk factor for case fatality and poor short-term prognosis after a first acute myocardial infarction?"
            ]
        },
        {
            "id": "task847-ba15491af53a4763b5f03832ad66de1d",
            "input": "Patients with obstructive sleep apnea (OSA) and coronary artery disease have a poor long-term prognosis. It is unknown whether the coronary blood flow (CBF) response to OSA is appropriate for myocardial metabolic requirements. Therefore, CBF was assessed during OSA, before and after the development of coronary artery endothelial dysfunction.', 'University Hospital Animal Laboratory.', 'Newborn lambs.', 'Lambs were surgically instrumented for invasive hemodynamic monitoring and sleep-wake EEG recordings. A tracheostomy was inserted to control the upper airway and model OSA during sleep. Coronary artery endothelial dysfunction was created using infusions of lipopolysaccharide (LPS). The CBF response during OSA was assessed and compared to changes in myocardial work (rate-pressure product [RPP]), O2 saturation, and cortical arousal, before and after the LPS infusions.', 'During OSA, CBF increased by 8.6% +/- 2.4% above baseline in the pre-LPS condition and 8.8% +/- 1.9% post-LPS, peaking following termination of the respiratory event. Pre-LPS, change in CBF post-apnea was independently correlated with change in RPP (R2 = 0.50), minimum SpO2 (R2 = 0.11) and the presence of cortical arousal (R2 = 0.04) (P < 0.01, forward stepwise regression analysis). Following LPS, the only predictor of CBF was degree of O2 desaturation (R2 = 0.14, P < 0.05).",
            "output": [
                "Does coronary blood flow become uncoupled from myocardial work during obstructive sleep apnea in the presence of endothelial dysfunction?"
            ]
        },
        {
            "id": "task847-b218ae889f7749428e28001712709fc8",
            "input": "In HIV patients, disorders in glucose metabolism seem to be side effects of highly active antiretroviral therapy (HAART) which may be favoured by obesity, abdominal fat accumulation and familial disposition for diabetes mellitus (DM). The aim of our study was to identify patients at high risk for abnormalities in glucose metabolism taking into account HAART, familial disposition for DM and anthropometric parameters.', 'Plasma glucose, insulin, c-peptide and insulin resistance (homeostasis model assessment, HOMA) were determined in 44 HIV patients [16 without HAART, 19 with protease inhibitors (PI), 9 without PI (non-PI)] and in 11 healthy subjects. Glucose tolerance was determined by standard procedures. Body mass index (BMI), triceps skin fold thickness and waist circumference were measured and the waist-to-hip-ratio was calculated. Familial disposition for DM was assessed by questionnaire.', 'Impaired fasting glucose was observed in 28% of HAART-treated patients (21% with PI, 7% non-PI), in 13% of HAART-naive but none in healthy controls. 58% of PI, 44% of non-PI, 38% of HAART-naive and none of healthy controls had a HOMA-index > 2.5 which indicates insulin resistance. HAART-treated patients had significantly higher fasting glucose levels (PI: 97 +/- 11 mg/dL, p = 0.048; non-PI: 109 +/- 58 mg/dL, p = 0.009) compared to healthy controls (72 +/- 8 mg/dL). HOMA-Index was higher in PI treated patients (3.74 +/- 3.08) than in HIV negative controls (0.95 +/- 0.28, p = 0.018). The duration of HAART (p = 0.045), overweight and familial disposition for DM (p = 0.017) significantly affected fasting glucose among PI users. Waist circumference affected c-peptide (p = 0.046) concentration in these patients.",
            "output": [
                "Are overweight HIV patients with abdominal fat distribution treated with protease inhibitors at high risk for abnormalities in glucose metabolism - a reason for glycemic control?"
            ]
        },
        {
            "id": "task847-d3836fa941964b249384af966f095227",
            "input": "For years, Uniform Resource Locator (URL) decay or \"link rot\" has been a growing concern in the field of biomedical sciences. This paper addresses this issue by examining the status of the URLs published in MEDLINE abstracts, establishing current availability and estimating URL decay in these records from 1994 to 2006. We also reviewed the information provided by the URL to determine if the context that the author cited in writing the paper is the same information presently available in the URL. Lastly, with all the documented recommended methods to preserve URL links, we determined which among them have gained acceptance among authors and publishers.', 'MEDLINE records from 1994 to 2006 from the National Library of Medicine in Extensible Mark-up Language (XML) format were processed yielding 10,208 URL addresses. These were accessed once daily at random times for 30 days. Titles and abstracts were also searched for the presence of archival tools such as WebCite, Persistent URL (PURL) and Digital Object Identifier (DOI).', 'Results showed that the average URL length ranged from 13 to 425 characters with a mean length of 35 characters [Standard Deviation (SD) = 13.51; 95% confidence interval (CI) 13.25 to 13.77]. The most common top-level domains were \".org\" and \".edu\", each with 34%. About 81% of the URL pool was available 90% to 100% of the time, but only 78% of these contained the actual information mentioned in the MEDLINE record. \"Dead\" URLs constituted 16% of the total. Finally, a survey of archival tool usage showed that since its introduction in 1998, only 519 of all abstracts reviewed had incorporated DOI addresses in their MEDLINE abstracts.",
            "output": [
                "Do an update on Uniform Resource Locator ( URL ) decay in MEDLINE abstracts and measures for its mitigation?"
            ]
        },
        {
            "id": "task847-7b3e33b3c70a4d88bc75100408bdd05b",
            "input": "The current study sought to examine how changes in pain-related beliefs and coping responses are related to changes in pain interference and psychological functioning in individuals with spinal cord injuries (SCI) and pain. To measure longitudinal changes in these variables, respondents completed a survey that included measures of pain intensity, pain interference, and psychological functioning, as well as specific psychosocial variables (pain-related beliefs, coping, and social support) and then completed the same survey 6 months later; analyses included only the individuals who reported pain at both times (n = 40). Demographic and injury-related variables were also assessed, but none were found to be significantly associated with changes in functioning. Changes in catastrophizing and belief in one's ability to control pain were each significantly associated with changes in the outcome variables: Greater pain interference and poorer psychological functioning. Changes in specific coping strategies and social support were not predictors of changes in pain, interference, or psychological functioning. These findings support a biopsychosocial model of pain in persons with SCI. Intervention studies targeting maladaptive pain-related beliefs and catastrophizing may help to identify the causal nature of these relationships and may improve multidisciplinary treatment of pain in SCI.",
            "output": [
                "Do pain catastrophizing and beliefs predict changes in pain interference and psychological functioning in persons with spinal cord injury?"
            ]
        },
        {
            "id": "task847-6f78b34e743b49ec8fe5ced0b67ec15e",
            "input": "Health scenarios are constantly evolving, particularly in developing countries but little is known regarding the health status of indigenous groups in Malaysia. This study aims to elucidate the current health status in four indigenous populations in the country, who by and large been left out of mainstream healthcare developments.', 'Participants were recruited from the Temuan, Jehai, Kensiu and Bidayuh indigenous groups throughout Peninsula Malaysia and Sarawak. Health parameters including body mass index (BMI), blood pressure, casual blood glucose and, total cholesterol levels were measured using established methods. Malondialdehyde (MDA) and ferric-reducing antioxidant power (FRAP) levels were measured to assess oxidative stress status. Blood films were screened for evidence of microbial or parasitic infections and leukocyte differential counting was performed.', 'The Temuan and Bidayuh who are more urbanized, had significantly higher mean body weight, BMI, total cholesterol (p<0.05) and higher prevalence of obesity and hypercholesterolemia. Low cholesterol levels, elevated eosinophil counts and increased total IgE, indicative of immune responses to infection or allergy, were recorded in the rural Kensiu and Jehai. The Kensiu had higher levels of FRAP and lower levels of MDA, whereas the reverse was found in the Temuan. This suggests reduced oxidative stress in the Kensiu compared to the Temuan. Expected correlations between FRAP and MDA levels with age, were evident in Jehai.",
            "output": [
                "Do an update of the general health status in the indigenous populations of Malaysia?"
            ]
        },
        {
            "id": "task847-f9b85cc3518c487b9b809b18801dab9c",
            "input": "Survivin is an anti-apoptotic protein that has been recently suggested as a predictive marker of joint destruction in adult rheumatoid arthritis. We assessed the presence of extracellular survivin in patients with juvenile idiopathic arthritis (JIA).', 'Survivin levels were assessed in the circulation of 46 patients with JIA and in the age- and gender-matched controls (n=46) having no inflammatory disease, by ELISA. Survivin levels were analyzed with respect to the onset type and the activity of the joint disease. The intensity of inflammation and cartilage turnover was measured as levels of IL-6, serum amyloid A protein (SAA), and cartilage oligomeric matrix protein (COMP), respectively.', 'The levels of extracellular survivin were significantly higher in JIA compared to the controls (p=0.0002). High levels of survivin (above mean + 2SD of the controls) were detected in 8/46 (17% JIA patients. High survivin expression was associated with polyarticular onset, active phase of arthritis. In contrast, survivin was neither related to the levels of IL-6, SAA, nor to COMP.",
            "output": [
                "Does circulating survivin indicate severe course of juvenile idiopathic arthritis?"
            ]
        },
        {
            "id": "task847-540152beed1649ab8dfda04d3792f749",
            "input": "Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function.', 'We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support.', 'Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome.",
            "output": [
                "Do donor postextubation hypotension and age correlate with outcome after donation after cardiac death transplantation?"
            ]
        },
        {
            "id": "task847-1ee084e508374cfc9bda132d7bd2a49d",
            "input": "Botulinum toxin type A (BTX-A) has been reported to have analgesic effects independent of its action on muscle tone, possibly by acting on neurogenic inflammation. Such a mechanism may be involved in peripheral neuropathic pain.', 'A possible direct analgesic effect of BTX-A pain processing was investigated in 29 patients with focal painful neuropathies and mechanical allodynia using a randomized, double-blind, placebo-controlled design. Patients received a one-time intradermal administration of BTX-A (20-190 units) into the painful area. Outcome measures, evaluated at baseline, then at 4, 12, and 24 weeks, included average spontaneous pain intensity, quantified testing of thermal and mechanical perception and pain, allodynia to brushing (area, intensity), neuropathic symptoms, clinical global impression, and quality of life.', 'BTX-A treatment, relative to placebo, was associated with persistent effects on spontaneous pain intensity from 2 weeks after the injection to 14 weeks. These effects correlated with the preservation of thermal sensation at baseline (p < 0.05). BTX also improved allodynia to brush and decreased pain thresholds to cold, without affecting perception thresholds. There were sustained improvements in the proportion of responders (number needed to treat for 50% pain relief: 3.03 at 12 weeks), neuropathic symptoms, and general activity. Most patients reported pain during the injections, but there were no further local or systemic side effects.",
            "output": [
                "Does botulinum toxin type A induce direct analgesic effects in chronic neuropathic pain?"
            ]
        },
        {
            "id": "task847-ba9f0b223b3f41b9940195a7719f5a45",
            "input": "The objective was to evaluate the prevalence of paroxysmal atrial fibrillation (PAF) in patients with heart failure (HF) due to systolic dysfunction.', 'We included 79 patients (age 68 years, LVEF 30%) with HF and sinus-rhythm (SR) referred to a HF outpatient clinic. A 48 hours Holter ECG and a follow-up ECG were performed. RESULTS. One patient had one episode of PAF. Thirty-two (41%) patients had episodes of irregular atrial runs (AR). The numbers of QRS complexes during AR were 7.2+/-2.9 (mean+/-SD). Patients with AR were older than patients with SR, p =0.02 and more often of female sex, p =0.04. Multivariate logistic regression analysis showed that age and female sex were independently correlated with AR with adjusted OR of 1.1 (per year, 95% CI 1.02-1.14, p =0.01) and 4.0 (1.05-15.07, p =0.04), respectively. The presence of AR did not predict development of new-onset AF.",
            "output": [
                "Is paroxysmal atrial fibrillation uncommon in outpatients with chronic heart failure?"
            ]
        },
        {
            "id": "task847-6f9ed06873414547a4385298e073a566",
            "input": "We examined the use of occupational therapy services in a sample of people aging with multiple sclerosis (MS).', 'A total of 1,282 people with MS, ages 45 to 90, participated in telephone interviews to identify unmet health-related service needs. Occupational therapy was 1 of 22 services examined. Proportional odds models were used to examine factors associated with how recently services were used.', 'Four hundred eighty-four participants (38.2%) had used occupational therapy services at some point since their diagnosis; 211 had used these services in the year before the interview. Recent users identified occupational therapy services as important to health and well-being. Satisfaction with services was high. Greater activity limitations and living in an urban or suburban area were associated with more recent use of occupational therapy services.",
            "output": [
                "Do occupational therapy service use among people aging with multiple sclerosis?"
            ]
        },
        {
            "id": "task847-a20c846bee744757bb34b8e749b5b207",
            "input": "This study examined interrater reliability of score interpretation on the Sensory Integration and Praxis Tests (SIPT).', 'Using SIPT scores of two complex cases, 20 trained participants independently rated each case for presence of sensory integrative dysfunction and for relevance of specific patterns of dysfunction. They also provided comments to justify their ratings.', 'Agreement on the presence of sensory integrative dysfunction was 70% for Case A and 100% for Case B. Reliability was more variable for dysfunctional pattern ratings, ranging from 50% to 100% agreement for Cases A and B, respectively. Participants consistently appeared to use configural decision-making strategies to guide their ratings.",
            "output": [
                "Do interrater reliability of Sensory Integration and Praxis Tests ( SIPT ) score interpretation?"
            ]
        },
        {
            "id": "task847-6475ad0261f9429e920435449b1fa531",
            "input": "The extracellular interactions of plasma clotting factor VIIa (FVIIa) with tissue factor (TF) on the cell surface trigger intracellular signaling events involved in multiple physiological processes. TF expression is related to the metastatic potential of tumor cells and is a significant risk factor in the development of hepatic metastases in patients with colorectal cancer. At present, it is unclear how the interaction between TF and FVIIa influences the development of metastasis in colon cancer.', 'We used a stable LOVO cell line derived from colorectal adenocarcinoma for our model Western blot analysis, Northern blot analysis, polymerase chain reaction, and RNA inference (RNAi), and the Dual-Luciferase Reporter Assay System technology were utilized to determine if MMP7 can be up-regulated by the VIIa/TF complex.', 'Northern blot analysis confirmed that the plasma clotting factor FVIIa/TF complex resulted in a marked increase in MMP7 expression in a time- and dose-dependent manner via the p38 pathway in vitro. The proximal promoter of the human MMP7 gene was cloned into a luciferase reporter construction (MMP7.luc1592). Upon treatment with FVIIa, reporter activity in LOVO cells was increased by 2.5-fold. TF RNAi almost completely abolished FVIIa-mediated MMP7.luc induction. Deletion constructs from MMP7.luc1592 further defined an active promoter region.",
            "output": [
                "Does the FVIIa-tissue factor complex induce the expression of MMP7 in LOVO cells in vitro?"
            ]
        },
        {
            "id": "task847-693c73e7de0c4164a199ab58c4036bc3",
            "input": "The \"hygiene hypothesis\" postulates that individuals raised in a sanitary environment are more likely to develop inflammatory bowel disease (IBD). Several studies previously demonstrated contradictory results in this regard. We performed for the first time a population-based study on the association of surrogate markers of childhood hygiene with the risk for IBD.', 'A cross-sectional population-based study was undertaken. Information on number of siblings, birth order, and living in an urban versus rural environment was obtained for 399,251 Jewish adolescents at the age of 17 yr from 1998 to 2004. The study population included only subjects born in Israel. In order to control for genetic confounding, subjects were also divided according to their ethnic group as being Ashkenazi, Sephardic, or Israeli in origin.', 'In total, 768 cases of inflammatory bowel disease (IBD) were diagnosed (0.19%), with 53.8% of the cases being of Ashkenazi origin. On multivariate analysis, variables significantly associated with IBD were male gender (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.24-1.67), Ashkenazi origin (OR 1.91, 95% CI 1.63-2.22), living in an urban environment (OR 1.38, 95% CI 1.02-1.78), small number of siblings in the family (for 1 sibling vs 5 or more, OR 2.63, 95% CI 1.49-4.62), and higher birth order (for birth order of 5 or higher vs 1, OR 2.35, 95% CI 1.47-3.77), showing for both variables an almost strictly highly significant monotonic association (P value for trend <0.001).",
            "output": [
                "Is childhood hygiene associated with the risk for inflammatory bowel disease : a population-based study?"
            ]
        },
        {
            "id": "task847-55b961e213dd425bb47ae4c1de19708c",
            "input": "Application of antibodies against cardiac troponin I (cTnI-Ab) can induce dilation and dysfunction of the heart in mice. Recently, we demonstrated that immunization with cTnI induces inflammation and fibrosis in myocardium of mice. Others have shown that auto-antibodies to cTnI are present in patients with acute coronary syndrome, but little is known about the clinical relevance of detected cTnI-Ab.', 'First, anti-cTnI and anti-cTnT antibody titres were measured in sera from 272 patients with dilated- (DCM) and 185 with ischaemic- (ICM) cardiomyopathy. Secondly, 108 patients with acute myocardial infarction (AMI) were included for a follow-up study. Heart characteristics were determined by magnetic resonance imaging 4 days and 6-9 months after AMI. Altogether in 7.0% of patients with DCM and in 9.2% with ICM, an anti-cTnI IgG antibody titre >/=1:160 was measured. In contrast, only in 1.7% of patients with DCM and in 0.5% with ICM, an anti-cTnT IgG antibody titre >/=1:160 was detected. Ten out of 108 patients included in the follow-up study were tested positive for cTnI-Ab with IgG Ab titres >/=1:160. TnI-Ab negative patients showed a significant increase in left ventricular ejection fraction (LVEF) and stroke volume 6-9 months after AMI. In contrast, there was no significant increase in LVEF and stroke volume in TnI-Ab positive patients.",
            "output": [
                "Does absence of auto-antibodies against cardiac troponin I predict improvement of left ventricular function after acute myocardial infarction?"
            ]
        },
        {
            "id": "task847-d2e14c04dd634ae781efb3a83157fc04",
            "input": "Human ZR75-1 cells were among the first few characterized estrogen-dependent mammary gland carcinoma cell lines and had been utilized in various studies for the pro- or antitumor effect of xenoestrogens and antiestrogens. The objective of this study was to establish a breast tumor model in ZR75-1 cells bearing multimodal reporter genes to allow noninvasive imaging of tumor growth using fluorescence and nuclear imaging platforms.', 'Enhanced green fluorescent protein (eGFP) cDNA was fused at the C-terminus with herpes simplex virus type 1 thymidine kinase (HSV1-tk) to form the fusion reporter gene (eGFP-tk). In vitro proliferation, migration, and invasion assays revealed that eGFP-tk-transfected ZR75-1 cells exhibited decreased proliferation rate, migratory activity, and invasion ability compared to the wild-type cells. The functional HSV1-tk enzymatic activity in stably transfected cells were confirmed by in vitro ganciclovir (GCV) sensitivity and [123I]2-fluoro-2-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (FIAU) accumulation assays. In vivo fluorescence and nuclear imaging were performed on nude mice bearing multiple subcutaneous xenografts established from ZR75-1-eGFP-tk and wild-type cells. Optical imaging was able to detect the green fluorescence of eGFP-tk tumor. The eGFP-tk reporter gene-specific imaging was achieved by single photon emission computed tomography (SPECT) using [123I]FIAU as a radiotracer and demonstrated decreased FIAU uptake in eGFP-tk tumor by GCV treatment. Probably due to a flare reaction after GCV treatment, micro-positron emission tomography (micro-PET) imaging using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) could not demonstrate decreases in FDG uptake. However, in vitro metabolic assay also revealed that eGFP-tk cells transiently increased [3H]-deoxyglucose uptake in response to GCV treatment.",
            "output": [
                "Do human breast tumor cells express multimodal imaging reporter genes?"
            ]
        },
        {
            "id": "task847-0caf113dcc7a47f48b4cc2d0850bba5e",
            "input": "Stomatal guard cells monitor and respond to environmental and endogenous signals such that the stomatal aperture is continually optimised for water use efficiency. A key signalling molecule produced in guard cells in response to plant hormones, light, carbon dioxide and pathogen-derived signals is hydrogen peroxide (H(2)O(2)). The mechanisms by which H(2)O(2) integrates multiple signals via specific signalling pathways leading to stomatal closure is not known.', 'Here, we identify a pathway by which H(2)O(2), derived from endogenous and environmental stimuli, is sensed and transduced to effect stomatal closure. Histidine kinases (HK) are part of two-component signal transduction systems that act to integrate environmental stimuli into a cellular response via a phosphotransfer relay mechanism. There is little known about the function of the HK AHK5 in Arabidopsis thaliana. Here we report that in addition to the predicted cytoplasmic localisation of this protein, AHK5 also appears to co-localise to the plasma membrane. Although AHK5 is expressed at low levels in guard cells, we identify a unique role for AHK5 in stomatal signalling. Arabidopsis mutants lacking AHK5 show reduced stomatal closure in response to H(2)O(2), which is reversed by complementation with the wild type gene. Over-expression of AHK5 results in constitutively less stomatal closure. Abiotic stimuli that generate endogenous H(2)O(2), such as darkness, nitric oxide and the phytohormone ethylene, also show reduced stomatal closure in the ahk5 mutants. However, ABA caused closure, dark adaptation induced H(2)O(2) production and H(2)O(2) induced NO synthesis in mutants. Treatment with the bacterial pathogen associated molecular pattern (PAMP) flagellin, but not elf peptide, also exhibited reduced stomatal closure and H(2)O(2) generation in ahk5 mutants.",
            "output": [
                "Does the histidine kinase AHK5 integrate endogenous and environmental signals in Arabidopsis guard cells?"
            ]
        },
        {
            "id": "task847-a40c7449391c49b68300133a07f6ffcc",
            "input": "Gastrin and pepsinogens reflect the functional state of the gastric mucosa.', 'To evaluate whether serum gastrin and pepsinogens correlate with the different grades of severity of gastro-oesophageal reflux disease (GERD).', \"In all, 388 patients with heartburn not taking any form of acid suppressive therapy were matched-controlled for age and gender and sub-classified into four groups: group 1 non-erosive reflux disease (NERD); group 2, erosive reflux disease (ERD) Los Angeles (LA) A and B, group 3, ERD LA C and D; group 4 Barrett's oesophagus (BO). Fasting serum was analysed for gastrin 17, pepsinogen I, pepsinogen II und Helicobacter pylori using specific EIA tests (GastroPanel; Biohit, Plc).\", 'Kruskal-Wallis test and analysis of variance.', 'There was a significant difference among the four groups with respect for pepsinogen I, but not for pepsinogen II, the pepsinogen I pepsinogen II ratio, H. pylori serology and gastrin levels. Pepsinogen I was the lowest in NERD and the highest in BO (median 91.6, mean +/- standard deviation 106.2 +/- 51.6 vs. median 114.7, mean +/- standard deviation 130.4 +/- 70.6; P = 0.046). Pepsinogen I levels were higher in H. pylori positive subjects. After adjusting for H. pylori status, the differences in pepsinogen I across patient groups were no longer statistically significant (P = 0.298).",
            "output": [
                "Do serum gastrin and pepsinogens correlate with the different grades of severity of gastro-oesophageal reflux disease : a matched case-control study?"
            ]
        },
        {
            "id": "task847-8c6ad62e305e41a9a641a26122392200",
            "input": "The natural history of cognitive impairment in multiple sclerosis (MS) and its relationship with disease activity is not well known. In this study, we evaluate a prospective cohort of 44 MS patients who were followed every 3 months for 2 years. Cognitive evaluation was done at baseline and by the end of the study using the Brief Repeatable Battery-Neuropsychology. Clinical evaluation included assessment of new relapses and changes in disability (Extended Disability Status Scale (EDSS)) confirmed at 6 months.', 'We found that verbal memory performance deteriorates after 2 years in patients with MS. These changes were observed in stable and active patients both in terms of relapses and disability progression, even at the beginning of the disease, and in patients with or without cognitive impairment at study entry. Attention and executive functions measured with the symbol digit modality test (SDMT) declined after 2 years in patients with confirmed disability progression. Furthermore, SDMT performance correlated with the EDSS change.",
            "output": [
                "Does memory decline evolve independently of disease activity in MS?"
            ]
        },
        {
            "id": "task847-d2448d039eb64a7aa73d802700a0eef4",
            "input": "The aim of this study was to evaluate the prognostic value of the serum CA-125 level for complete responders after 6 cycles of primary adjuvant paclitaxel/carboplatin chemotherapy in advanced epithelial ovarian cancer.', 'The clinical data of 123 complete responders after 6 cycles of primary adjuvant paclitaxel/carboplatin chemotherapy for epithelial ovarian cancer FIGO stages III and IV were collected between January 1997 and March 2007. All patients were divided into 3 groups according to the serum CA-125 level after 6 cycles of the chemotherapy: group I (< 10 U/ml), group II (10-21 U/ml), and group III (> 21 U/ml). The effect of the serum CA-125 level on survival was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis.', 'The median progression-free survival was 26, 14, and 10 months, and the median overall survival was 105, 42, and 37 months in groups I, II, and III, respectively (p < 0.05). The lower serum CA-125 level and optimal debulking surgery were prognostic factors for improving survival (p < 0.05).",
            "output": [
                "Is serum CA-125 level after 6 cycles of primary adjuvant chemotherapy a useful prognostic factor for complete responders ' survival in patients with advanced epithelial ovarian cancer?"
            ]
        },
        {
            "id": "task847-fc15c7164a814edabcdb45ccf12bbc4a",
            "input": "The clinical significance of chemokine receptor CCR7 expression in pancreatic ductal cancer was investigated.', 'Immunohistochemical staining of 89 pancreatic cancers treated macroscopically with curative resection without hematogenous metastases or peritoneal dissemination were analyzed in association with clinicopathological data.', 'The positivity of CCR7 in pancreatic cancer was 32.6% (29/89). A significant correlation was detected between CCR7-positive expression and lymph node metastasis. Patients with CCR7-positive tumors had significantly shorter survival times than those with CCR7-negative tumors (median, 12.8 vs. 21.9 months, respectively; p = 0.0039). CCR7 expression was an independent prognostic factor (hazard ratio, 1.949; p = 0.0364) by multivariate survival analysis; however, it was not an indicator for any particular site of recurrence.",
            "output": [
                "Does chemokine receptor CCR7 expression correlate with lymph node metastasis in pancreatic cancer?"
            ]
        },
        {
            "id": "task847-229e86573268422c99c4fb7df2f08120",
            "input": "XIAP-associated factor 1 (XAF1) is a tumor suppressor gene, but its role in angiogenesis is unknown. We investigated whether XAF1 has any antiangiogenesis effect.', 'MS1 (a mouse endothelial cell line) was infected with an adenoviral vector ZD55-XAF1. Controls were uninfected or infected with ZD55-EGFP. Wound healing assay and tube formation assay were used to assess angiogenesis. Cell proliferation was detected by WST-1 assay, and apoptosis was detected by TUNEL and APOPercentagetrade mark assays.', 'ZD55-XAF1 significantly upregulated XAF1, which was associated with decreased cell proliferation, migration and tube formation of MS1 cells. Ectopic overexpression of XAF1 induced apoptosis in MS1 and also sensitized cells to 5-fluorouracil-induced apoptosis. A significant decrease in the expression of Tie-1, Ang-1, Ang-2 and c-Myc was observed.",
            "output": [
                "Does xIAP-associated factor 1 ( XAF1 ) suppress angiogenesis in mouse endothelial cells?"
            ]
        },
        {
            "id": "task847-f60b1430b21049baaaf9b05ba6446125",
            "input": "Records of patients who had repair of sinus venosus defect (SVD) between 1970 and 2008 were reviewed to predict very long-term outcome.', 'Repairs occurred in 104 consecutive patients (51 men), aged 29 +/- 23 years (range, 1 to 70 years). Seven had isolated SVD and 97 had associated lesions that required concomitant operations. Five patients had preoperative arrhythmias; 24 (23%) were in New York Heart Association (NYHA) class III to V. Single-patch repair was done in 91 patients, caval translocation (Warden) in 7, and double-patch in 6.', 'Ten late deaths during 38 years of follow-up (mean, 15 +/- 20 years). Survival was 97% +/- 2% and 79% +/- 7% at 10 and 30 years. Thirty-one (29%) long-term survivors experienced 47 complications, including chronic/recurrent supraventricular tachycardia in 28, heart failure in 5, permanent pacing in 8, cerebrovascular accident in 3, and unrelated cardiac reoperation in 3. At 30 years, freedom from adverse cardiac events was 47% +/- 9%, from supraventricular tachycardia, 50% +/- 9%; from permanent pacing, 83 +/- 6%; and from cerebrovascular accident, 96% +/- 2%. Follow-up age was 42 +/- 23 years (range, 5 to 82 years); 74 patients (79%) were in NYHA class I, and 15 and 5 were in class II and III to IV, respectively. Baseline cardiac rhythm was sinus in 75 patients (84%), atrial fibrillation in 11 (12%), and paced in 8. Nine patients had moderate/severe pulmonary hypertension, and 8 had left ventricular dysfunction. Only older age at operation was associated with lower survival (p = 0.003), freedom from cardiac events (p = 0.001), supraventricular tachycardia (p = 0.009), and permanent pacing (p = 0.002). Repair before age 20 was associated with lower NYHA class at follow-up (p = 0.01).",
            "output": [
                "Does age at repair affect the very long-term outcome of sinus venosus defect?"
            ]
        },
        {
            "id": "task847-0cb68f924f5e46caa3566dbdba521545",
            "input": "Magnesium (Mg) is an essential cofactor for enzymes involved in glucose and insulin metabolism. Low intakes of dietary magnesium may be linked to greater risk of metabolic syndrome (MS) in older adults.', 'The objective of this study was to examine the cross-sectional relationship between dietary Mg intake, metabolic risk factors and MS in elderly adults.', 'This study was conducted in a sample of 535 (179 men and 356 women) community-living adults aged 60 years and in Boston Massachusetts between the years 1981 and 1984. Dietary Mg intake was assessed by a 3-day food record and categorized by quartiles of dietary intake. The MS was defined based on criteria set by the Third Report of the National Cholesterol Education Program except that body mass index was used in place of waist circumference. Logistic regression analysis was used to examine the association between quartile categories of Mg intake, prevalence of MS and components of the MS. Models were adjusted for age, gender, BMI, race, educational attainment, marital status, smoking status, alcohol intake, exercise, energy intake, percentage of calories from saturated fat, use of antihypertensive or lipid medication.', 'Mg intake was inversely associated with the MS; those with the highest intake of Mg had significantly lower risk of having MS compared to the lowest quartile of intake (OR: 0.36, 95% CI 0.19-0.69, P for trend 0.002). Significant inverse relationships were observed between Mg intake and BMI (OR: 0.47, 95% CI: 0.22-1.00, P trend = 0.03), and fasting glucose (OR: 0.41, 95% CI 0.22-0.77, P trend = 0.005).",
            "output": [
                "Is dietary magnesium intake related to metabolic syndrome in older Americans?"
            ]
        },
        {
            "id": "task847-4b47193fcda8455ea6ec7c45a5330436",
            "input": "Islet cell transplantation can cure type 1 diabetes (T1D), but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.', 'Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG) induction and tacrolimus plus mycophenolate mofetil (MMF) maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively) and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively). Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.",
            "output": [
                "Does cellular islet autoimmunity associate with clinical outcome of islet cell transplantation?"
            ]
        },
        {
            "id": "task847-90517590e4994310ae8dec0e41f2115a",
            "input": "Thrombin influences the biological behavior of periodontal ligament cells and plays multiple roles in the early stages of bone healing. Osteoprotegerin (OPG) is one of the key molecules that regulate bone homeostasis and prevent osteoclastogenesis. The purpose of this study was to evaluate the biological effects of thrombin on OPG synthesis in human periodontal ligament (HPDL) cells in vitro.', 'Cells were treated with various concentrations (0.001, 0.01 and 0.1 U/mL) of thrombin. The mRNA expression and protein synthesis of OPG, as well as of receptor activator of nuclear factor kappaB ligand (RANKL), were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. The influence of thrombin on OPG synthesis and its signaling pathway were investigated using inhibitors.', \"Thrombin profoundly induces protein synthesis of OPG at 0.1 U/mL. The inductive effect was inhibited by cycloheximide, but not by indomethacin. The phosphatidylinositol 3'-kinase (PI3K) inhibitor, LY294002, and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exerted an inhibitory effect on the thrombin-induced OPG synthesis. In addition, the effect was inhibited by protease-activated receptor (PAR)-1 antagonist. Activation of phospho-Akt (p-Akt) was observed and the effect was abolished by LY294002.",
            "output": [
                "Does thrombin induce osteoprotegerin synthesis via phosphatidylinositol 3'-kinase/mammalian target of rapamycin pathway in human periodontal ligament cells?"
            ]
        },
        {
            "id": "task847-82b98e14d3c54fbb99ce0d737c4f1318",
            "input": "Despite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes.', 'Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals.",
            "output": [
                "Does whole genome assessment of the retinal response to diabetes reveal a progressive neurovascular inflammatory response?"
            ]
        },
        {
            "id": "task847-10b9f30f3c754889873b4841d2420a2c",
            "input": "We investigated whether luciferase immunoprecipitation systems (LIPS) can be the basis for a more rapid, specific, and standardized assay for the diagnosis of Strongyloides stercoralis infection.', 'A LIPS assay was developed based on immunoglobulin (Ig) G or IgG4 antibody to a recombinant Strongyloides antigen (NIE) and was compared with an NIE enzyme-linked immunosorbent assay (ELISA). A second antigen, S. stercoralis immunoreactive antigen (SsIR), was tested alone and in combination with NIE. The assays were tested using serum samples from patients with parasitologically proven S. stercoralis or filarial infections and from healthy, uninfected control subjects.', 'The NIE LIPS assay based on IgG antibody easily differentiated between S. stercoralis-infected and uninfected patients (P< .0001) and demonstrated improved specificity compared with the NIE ELISA (100% vs. 95%). Serum from filaria-infected patients did not cross-react when tested with the NIE LIPS assay. When SsIR was used in combination with NIE in the LIPS format, sensitivity and specificity improved to 100%, with a 7-fold difference between positive and negative values. No advantage was found in using a LIPS assay based on IgG4. At posttreatment follow-up, a significant decline in antibody titers was detected using the NIE ELISA (P< .0017) and the NIE LIPS assay (P< .0001).",
            "output": [
                "Does a luciferase immunoprecipitation systems assay enhance the sensitivity and specificity of diagnosis of Strongyloides stercoralis infection?"
            ]
        },
        {
            "id": "task847-b4c6ab22a47e4b128739017161b71918",
            "input": "To describe a new entity of congenital muscular dystrophies caused by de novo LMNA mutations.', 'Fifteen patients presenting with a myopathy of onset in the first year of life were subjected to neurological and genetic evaluation. Histopathological and immunohistochemical analyses were performed for all patients.', 'The 15 patients presented with muscle weakness in the first year of life, and all had de novo heterozygous LMNA mutations. Three of them had severe early-onset disease, no motor development, and the rest experienced development of a \"dropped head\" syndrome phenotype. Despite variable severity, there was a consistent clinical pattern. Patients typically presented with selective axial weakness and wasting of the cervicoaxial muscles. Limb involvement was predominantly proximal in upper extremities and distal in lower extremities. Talipes feet and a rigid spine with thoracic lordosis developed early. Proximal contractures appeared later, most often in lower limbs, sparing the elbows. Ten children required ventilatory support, three continuously through tracheotomy. Cardiac arrhythmias were observed in four of the oldest patients but were symptomatic only in one. Creatine kinase levels were mild to moderately increased. Muscle biopsies showed dystrophic changes in nine children and nonspecific myopathic changes in the remaining. Markedly atrophic fibers were common, most often type 1, and a few patients showed positive inflammatory markers.",
            "output": [
                "Do de novo LMNA mutations cause a new form of congenital muscular dystrophy?"
            ]
        },
        {
            "id": "task847-0ed3dc364d064e448d4038b9107f3e2e",
            "input": "Some subjects with suspected asthma and a negative exercise challenge test (ECT) demonstrate improved expiratory flow rates after administration of bronchodilators (BD) at the end of the ECT (unpublished observation). This study investigated whether this response predicts the presence of bronchial hyperreactivity (BHR).', 'The study population included 133 young adults (29.4% women) 21.1 +/- 4.2 years of age who underwent ECT and a methacholine challenge test (MCT). A receiver-operator-characteristic curve was used to calculate the optimal cutoff level of the response to BD as a predictor of BHR according to MCT.', 'Using a MCT cutoff level of PC(20) </= 4 mg/mL showed BHR in 12.8% of subjects. Failure to improve FEV(1) by 8% after BD administration predicted the absence of BHR with sensitivity, specificity, and positive and negative predictive values of 76.5%, 68.4%, 25.3%, and 95.5%, respectively. Avoiding MCT in subjects with less than 8% response to BD would have saved 62.5% of the MCTs and would have missed only four (3%) patients with BHR.",
            "output": [
                "Does response to bronchodilators after exercise challenge predict bronchial hyperreactivity?"
            ]
        },
        {
            "id": "task847-793a92cf46d54caea3bd5bd40402971c",
            "input": "The clinical significance of the hepatitis B virus core-related antigen (HBcrAg) assay in monitoring the antiviral effects of lamivudine is reviewed.', 'The HBcrAg assay simultaneously measured serum levels of hepatitis B core (HBc) and e (HBe) antigens using monoclonal antibodies which recognize common epitopes of these two denatured antigens.', 'Although serum HBcrAg levels correlated linearly with those of hepatitis B virus (HBV) DNA in natural course, the decrease in HBcrAg was significantly slower than in HBV DNA after initiation of lamivudine administration. We analyzed the clinical significance of HBV DNA and HBcrAg levels to predict the occurrence of lamivudine resistance. HBV DNA measurement may be useful to identify patients who are at high risk of developing lamivudine resistance, and HBcrAg measurement may help to detect patients who are at low risk of drug resistance. The measurement of HBcrAg was also found to be a useful prognosticator for reactivation of hepatitis after cessation of lamivudine administration.",
            "output": [
                "Is hepatitis B core-related antigen assay useful for monitoring the antiviral effects of nucleoside analogue therapy?"
            ]
        },
        {
            "id": "task847-4ac044f43f8840f7b2562cfe22f2179d",
            "input": "Studies suggest ultraviolet (UV) A1 phototherapy is efficacious and safe in treating a variety of skin disorders. However, most reports evaluating the benefits of UVA1 phototherapy have been from Europe, focusing on a predominantly Caucasian population. Darker skin types have been evaluated only sparingly; none the less, it is widely held that these patients respond poorly to UVA1 phototherapy due to increased pigmentation.', 'We aim to compare efficacy (clinical improvement scores) of UVA1 phototherapy among Fitzpatrick skin types.', 'A retrospective analysis of 101 patients receiving UVA1 treatment at the University of Texas Southwestern Medical Center in Dallas, TX was performed. Data on Fitzpatrick skin type and cumulative UVA1 doses were collected. Clinical improvement scores based on body surface area, erythema, induration, sclerosis, pigmentation, and symptoms of pain or pruritus were obtained.', 'In the population studied, with morphoea and scleroderma being the most frequent diagnoses, improvement scores from UVA1 phototherapy and mean cumulative UVA1 doses were not significantly different among the Fitzpatrick skin types evaluated. Furthermore, little or no correlation was found between improvement score and skin type.",
            "output": [
                "Is uVA1 phototherapy effective in darker skin : a review of 101 patients of Fitzpatrick skin types I-V?"
            ]
        },
        {
            "id": "task847-1a3b05ba8b5d4af18e8dc98f780457d0",
            "input": "Substance use among husbands has been shown to be associated with higher rates of substance use and of psychiatric symptoms among their wives. However, substance use disorders (SUD) and psychiatric disorders (as opposed to substance use or psychiatric symptoms) are rarely rigorously assessed among large samples of couples, so it is unclear whether SUD among husbands are associated with SUD among their wives, and whether the wives also display a higher prevalence of co-occurring or non-co-occurring psychiatric disorders. We compared the level of SUD, of co-occurring (with SUD) psychiatric disorders, and of non-co-occurring psychiatric diagnoses among the wives of males with SUDs vs among the wives of males without SUDs. We hypothesized that the presence of SUDs among males would be associated with a higher level of SUDs, of co-occurring psychiatric disorders, and of non-co-occurring psychiatric disorders in their wives.', 'The subjects in this study were the spouses of adult men with a lifetime history of an SUD (SUD+ husbands, N=342) vs those with no lifetime history of an SUD (SUD- husbands, N=350). These subjects were recruited for participation in a longitudinal project designed to elucidate the etiology of substance use disorders.', 'Co-occurring SUDs were five times more common among the spouses of SUD+ husbands than among the spouses of SUD- husbands (10.2% vs 2.0%, chi-square=19.7, p=0.000). SUD/depressive disorder and SUD/anxiety disorder were both seven times more common among the spouses of SUD+ husbands than among the spouses of SUD- husbands (19.4% vs 4.7%, chi-square=45.8, p=0.000; 14.3% vs 2.0%, chi-square=34.5, p=0.000). In contrast, non-co-occurring depressive disorders and non-co-occurring anxiety disorders were not more common among the wives of the SUD+ husbands than among the SUD- husbands.",
            "output": [
                "Is husbands ' SUD associated with higher levels of co-occurring but not non-co-occurring psychiatric disorders among their wives?"
            ]
        },
        {
            "id": "task847-663f2f9258c54094af54053e43a99a0f",
            "input": "To evaluate the effect of uterine leiomyomas on the endometrium using molecular markers of endometrial receptivity: HOXA10, HOXA11, LIF, and BTEB1.', 'Case-control study.', 'University medical center.', 'Thirty reproductive-aged women with submucosal, intramural, or no uterine myomas who underwent hysteroscopy or hysterectomy.', 'Proliferative phase endometrial sampling was performed at the time of surgery. In uteri with a submucosal myoma, directed endometrial biopsies were obtained over the myoma and over normal myometrium.', 'Endometrial HOXA10 expression was evaluated as a primary endpoint using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. HOXA11, BTEB1, and LIF were evaluated using real-time RT-PCR.', 'Endometrial HOXA10 and HOXA11 messenger RNA (mRNA) expression were significantly decreased in uteri with submucosal myomas compared with controls and with uteri with intramural myomas. A similar trend was seen in BTEB1 mRNA expression; however, no difference was found in LIF mRNA expression. Immunohistochemistry localized the decrease in endometrial HOXA10 protein expression to stroma. In the presence of a submucosal myoma, there were no regional differences in gene expression.",
            "output": [
                "Do submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity?"
            ]
        },
        {
            "id": "task847-4b14e3a2063e46c6a7b76754e61ced64",
            "input": "To examine the relationship between sperm strict morphology and sperm chromatin integrity.', 'Prospective study.', 'Infertility clinic.', 'Eighty-seven consecutive semen samples from non-azoospermic men presenting for infertility evaluation and 6 samples from fertile donors.', 'Assessment of standard semen parameters and sperm chromatin structure assay (SCSA) parameters (%DFI [DNA fragmentation index] and %HDS [high DNA stainability]). Evaluation of %HDS and %DFI after treatment with dithiothreitol (a thiol-reducing agent used to decondense sperm nuclei) was also undertaken.', 'Relationship between sperm strict morphology defects and SCSA parameters (%DFI and %HDS).', 'We observed significant relationships between the percentage of normal sperm forms and both %HDS (r = -0.40) and sperm motility (r = 0.32). We also found significant relationships between sperm head defects and both %HDS (r = 0.40) and sperm concentration (r = -0.39). Sperm tail, midpiece, and neck defects were not significantly related to the SCSA parameters. Treatment of spermatozoa with dithiothreitol (to induce decondensation) resulted in a substantial increase in %HDS but no measurable change in %DFI.",
            "output": [
                "Is sperm head morphology related to high deoxyribonucleic acid stainability assessed by sperm chromatin structure assay?"
            ]
        },
        {
            "id": "task847-bcfba805ef6245e5bb9a6be5c0221a3e",
            "input": "Because of its inherent risks, ERCP should only be performed for purposes of treatment. EUS and MRCP have emerged as diagnostic alternatives before therapeutic ERCP.', 'Our purpose was to test the accuracy of EUS in predicting the need for therapeutic ERCP in low-risk patients.', 'Prospective, unblinded, single-center study.', 'Academic center of the University of Witten/Herdecke.', 'Fifty patients with clinical, laboratory, or transabdominal US findings suggestive of biliary obstruction were included.', 'After clinical assessment and US, all patients underwent EUS. If EUS was conclusive, either ERCP with sphincterotomy (EST) was performed or the patients were followed up for 1 year. If EUS was inconclusive, MRCP was performed, followed by ERCP or a 1-year follow-up. After each diagnostic step, the examiner decided whether any biliary conditon was present and whether therapeutic ERCP was necessary. The decicions were compared with the results of ERCP with EST or the outcome after the 1-year follow-up.', 'Accuracy of EUS in predicting the need for therapeutic ERCP.', 'Nine patients had ERCP with EST. The final assessment classified 2 of these interventions as having been unnecessary. EUS was conclusive in 49 cases. After EUS, the accuracy of the decision on the presence of a biliary condition increased from 82% to 96% and on the need for therapeutic ERCP from 86% to 96%.",
            "output": [
                "Does eUS accurately predict the need for therapeutic ERCP in patients with a low probability of biliary obstruction?"
            ]
        },
        {
            "id": "task847-4821b67839034cf1877bc200025a44b0",
            "input": "Childhood overweight and obesity have increased substantially in the past two decades, raising concerns about their psychosocial and cognitive consequences. We examined the associations between academic performance (AP), cognitive functioning (CF), and increased BMI in a nationally representative sample of children.', 'Participants were 2,519 children aged 8-16 years, who completed a brief neuropsychological battery and measures of height and weight as a part of the Third National Health and Nutrition Examination Survey, a cross-sectional survey conducted between 1988 and 1994. Z-scores were calculated for each neuropsychological test, and poor performance was defined as z-score <2.', 'The association between BMI and AP was not significant after adjusting for parental/familial characteristics. However, the associations between CF remained significant after adjusting for parental/familial characteristic, sports participation, physical activity, hours spent watching TV, psychosocial development, blood pressure, and serum lipid profile. Z-scores on block design (a measure of visuospatial organization and general mental ability) among overweight children and children at risk of overweight were below those of normal-weight children by 0.22 (s.e. = 0.16) and 0.10 (s.e. = 0.10) unit, respectively (P for trend <0.05). The odds of poor performance on block design were 1.97 (95% confidence interval: 1.01-3.83) and 2.80 (1.16-6.75), respectively, among children at risk or overweight compared to normal-weight peers.",
            "output": [
                "Is overweight associated with decreased cognitive functioning among school-age children and adolescents?"
            ]
        },
        {
            "id": "task847-8fee2d5adf7447139395bbc211836f74",
            "input": "TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS.', 'To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus.",
            "output": [
                "Is tDP-43 a common cause of sporadic amyotrophic lateral sclerosis?"
            ]
        },
        {
            "id": "task847-9674fb43fda543458a8010a437e9ae3f",
            "input": "Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer.', 'Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer.",
            "output": [
                "Do allogeneic lymphocytes persist and traffic in feral MHC-matched mauritian cynomolgus macaques?"
            ]
        },
        {
            "id": "task847-5b9275eec442459ba791a0ebdfdee8fa",
            "input": "To follow up a previous retrospective analysis in which we found the use of a pacifier to be a risk factor for recurrent acute otitis media (AOM).', 'In the present prospective study, the occurrence of AOM and the use of a pacifier were recorded in 845 children attending day care centers during a 15-month period.', 'More than three attacks of AOM occurred in 29.5% of the children younger than 2 years using pacifiers and in 20.6% of those not doing so (relative risk, 1.6; 95% confidence interval [CI], 0.6, 4.1); in children 2 to 3 years of age, the figures were 30.6% and 13.2%, respectively (relative risk, 2.9; 95% CI, 1.2, 7.3). Logistic modeling with adjustment for age and the duration of monitoring showed the occurrence of AOM to be associated with the time during which a pacifier was used. The use of a pacifier increased the annual incidence of AOM from 3.6 (95% CI, 2.5, 4.9) to 5.4 episodes (4.4, 6.6) in children younger than 2 years and from 1.9 (1.4, 2.5) to 2.7 (2.2, 3.3) in children 2 to 3 years of age. The population-attributable risk of AOM attacks due to the use of a pacifier was 176 attacks, ie, 459 to 635 attacks per year, in the youngest children and 69 attacks, ie, from 264 to 333 attacks per year, in those 2 to 3 years of age. It can be calculated that the use of a pacifier was responsible for 25% of the attacks in children younger than 3 years. Breastfeeding, parental smoking, thumb sucking, using a nursing bottle, and the social class of the family failed to show such strong associations with the occurrence of AOM.",
            "output": [
                "Does a pacifier increase the risk of recurrent acute otitis media in children in day care centers?"
            ]
        },
        {
            "id": "task847-8228f651c7df4158b365659a7da7a499",
            "input": "To correlate the initial and maximal lactate levels with the occurrence of intracranial hemorrhage (ICH) and survival in patients treated with extracorporeal life support (ECLS).', 'Retrospective chart review.', 'Pediatric intensive care unit.', 'Eighty-two neonatal patients placed on ECLS for respiratory failure due to sepsis, meconium aspiration, or persistent pulmonary hypertension of the newborn.', 'The initial lactate level measured within 6 hours of initiating ECLS and the maximal lactate level measured throughout the ECLS course were collected. Lactate levels were described as mean lactate +/- SE (mM). Head ultrasound reports and survival were reviewed. Platelet counts and activated clotting times (ACTs) were examined.', 'The mean initial and maximal lactate levels were higher in ECLS patients who developed ICH (initial: 10 +/- 1.7 mM vs 6.4 +/- 0.8 mM, p = .05 and maximal: 12.4 +/- 2.5 mM vs 7.9 +/- 0.8 mM, p = .04). Initial and maximal lactate levels were also elevated in nonsurvivors (initial: 11.7 +/- 3 mM vs 6.4 +/- 0.7 mM, p = .01 and maximal: 14.8 +/- 3.3 mM vs 7.8 +/- 0.8 mM, P < .01). Platelet counts and ACT did not differ in patients with and without ICH.",
            "output": [
                "Does elevated serum lactate correlate with intracranial hemorrhage in neonates treated with extracorporeal life support?"
            ]
        },
        {
            "id": "task847-9fd2c6f60c6341f88351ff8cdbd47a48",
            "input": "Psychodynamic clinicians cite defensive actions observed in evaluation and treatment as a source of important information. Empirical support for such assertions has seldom been based on objective study of recorded psychotherapy. A quantitative study of the association of signs of defensive control with disclosure of conflicted beliefs was undertaken.', 'Brief dynamic psychotherapies of two patients with pathological grief reactions were recorded and reviewed by independent judges. Periods of heightened defensive control of verbal and nonverbal communication were quantified using operational definitions. Reliably scored defensive episodes were algorithmically selected by computer programs. The people and topics discussed by patients were independently scored.', 'Highly defensive periods contained disproportionately more frequent instances of patient discourse about people involved in conflict and unresolved topics.",
            "output": [
                "Do signs of defensive control locate conflicted topics in discourse?"
            ]
        },
        {
            "id": "task847-b6cf85840fbf4350bd30db68ddb0dde9",
            "input": "To study further the temporal clustering of ankylosing enthesopathy (AE) noted originally during a study of the influence of mouse major histocompatibility complex (MHC) H-2 and transgenic HLA-B27 on the frequency of AE.', 'The relationship between maternal age at littering and frequency of AE was analysed.', 'Mice born to mothers aged eight months or older had a significantly lower disease frequency of AE than mice born to mothers younger than eight months of age. This phenomenon was observed in three independent cohorts evaluated to date (p < 0.01, 0.025, and 0.05).",
            "output": [
                "Does maternal age influence risk for HLA-B27 associated ankylosing enthesopathy in transgenic mice?"
            ]
        },
        {
            "id": "task847-6f443b220ea844558995f0e2d96fcf45",
            "input": "Microemboli released during transient ischemic attack, stroke, and cardiac surgery are thought to cause a variety of functional deficits in humans. The purpose of this study was to characterize the type and extent of neurobehavioral deficits present after photochemically induced common carotid artery thrombosis (CCAT), a thromboembolic model of stroke in the rat that results in a platelet emboli shower.', 'Thirty-two male Wistar rats were assigned to four groups. Groups 1 (n = 8) and 3 (n = 8) were long-term (6-week survival) and short-term (2-week survival) experimental groups subjected to right CCAT with the use of the photochemical technique. Groups 2 (n = 8) and 4 (n = 8) served as sham-operated controls for each experimental group. A battery of behavioral tests was applied daily beginning 24 hours after thrombosis; this consisted of elicited forelimb placing, postural reflex, beam balance, beam walking, and open field activity. Cognitive testing with a water maze task was performed on post-CCAT days 30 to 33 for groups 1 and 2 and on post-CCAT day 2 for groups 3 and 4. Ten-micrometer coronal brain sections were stained with hematoxylin and eosin, and infarct location and frequency were determined.', 'Significant sensorimotor deficits were observed, which recovered within 2 weeks after CCAT. The data that follow are derived by combining the two experimental groups and comparing these with the two sham groups. The following tests showed significant effects after CCAT: contralateral elicited forelimb placing, ipsilateral elicited forelimb placing, beam balance, and beam walking score. Cognitive dysfunction was seen acutely (group 3 animals) at 2 days after CCAT; Morris water maze length and latency to target were significantly greater in the experimental group. No deficits were seen in postural reflex, open field activity, or delayed cognitive testing. Histopathological assessment revealed small infarcts in 11 of 16 thrombosed rats. However, a strong relationship between neurobehavioral deficits and infarct location was not consistently demonstrated.",
            "output": [
                "Does nonocclusive common carotid artery thrombosis in the rat result in reversible sensorimotor and cognitive behavioral deficits?"
            ]
        },
        {
            "id": "task847-2757903266344c3ab6ae1b77c9176cad",
            "input": "Calf muscle pump dysfunction is a recognized factor in chronic venous insufficiency (CVI). We investigated the hypothesis that limbs with CVI have a reduced ankle range of motion (ROM) that may be responsible for the poor calf pump function associated with venous ulceration.', 'Ankle ROM and calf pump function were assessed in 32 limbs of 26 adult men. Limbs were selected on the basis of clinical presentation: normal (n = 6 limbs), class 1 or 2 CVI with no history of ulceration (n = 9 limbs), class 3 CVI with healed ulceration (n = 9 limbs), and class 3 CVI with active ulceration (n = 8 limbs). ROM was determined by goniometry during maximal plantar flexion and dorsiflexion of the ankle. Calf pump function was determined by air plethysmographic measurement of ejection fraction (EF) and residual volume fraction (RVF).', 'Ankle ROM was significantly (p < 0.05) reduced in each CVI group compared with age-matched control subjects, because of decreases in both plantar flexion and dorsiflexion. Calf pump function was significantly impaired (decreased EF and increased RVF) in ulcerated limbs. ROM was significantly correlated to EF and RVF. Impairment of ROM and calf pump function was associated with deterioration in the clinical classification of venous disease.",
            "output": [
                "Is limited range of motion a significant factor in venous ulceration?"
            ]
        },
        {
            "id": "task847-13846ed158b0439db4e815435868787b",
            "input": "To determine the influence of age on survival of patients undergoing resection for lung cancer.', 'Retrospective.', 'South-western part of the Netherlands.', 'Follow-up information was gathered on patients who had undergone resection for stage I non-small cell lung cancer from 1984 through 1990 and had been registered by the Rotterdam Cancer Registry. Operative mortality, 2-year and 5-year survival in the age groups 20-59, 60-69 and 70 years and older were compared.', 'Of the 630 patients (median age of 66 years) one-third was 70 years or older. Operative mortality was mainly determined by the type of operation: 6% after pneumonectomy versus 1% after lesser resections. Five-year survival declined with age from 65% to 48% and 43% (p < 0.01). After adjustment for non-related causes of death this difference decreased: 68%, 55%, 61% (p = 0.15). The main prognostic factor was tumour size.",
            "output": [
                "Does [ Good surgery result in older patients with stage 1 lung carcinoma ]?"
            ]
        },
        {
            "id": "task847-e6ec8e5540ef42ddb608fb19ccebec41",
            "input": "Amitriptyline and other tricyclic antidepressants exhibit high affinity binding to N-methyl-D-aspartate (NMDA) receptors in vitro and inhibit NMDA receptor activation-induced neuroplasticity in hippocampal slices. Because spinal NMDA receptor activation is believed to be central to generation and maintenance of hyperalgesic pain, the purpose of this study was to test whether intrathecal amitriptyline reduced inflammation-induced hyperalgesia in the rat.', 'Rats were prepared with chronic lumbar intrathecal and femoral intravenous catheters and nociceptive threshold was assessed by hind paw withdrawal to a radiant heat stimulus. Rats received an injection of carrageenin in one hind paw followed by thermal paw withdrawal testing 3 hr later and intrathecal amitriptyline and/or intravenous morphine injection. In other rats, intrathecal NMDA injection was preceded by either intrathecal saline or 60 micrograms amitriptyline.', \"Intrathecal amitriptyline reversed thermal hyperalgesia in a dose-dependent manner, but had no effect on withdrawal latency of the contralateral, noninjected paw. Intrathecal phentolamine plus methysergide did not alter amitriptyline's effect, except at the lowest dose. Intravenous morphine increased paw withdrawal latency in both inflamed and control paws in a dose-dependent fashion, and morphine interacted additively with intrathecal amitriptyline to reverse hyperalgesia. Thermal hyperalgesia induced by NMDA was completely antagonized by intrathecal amitriptyline.",
            "output": [
                "Does intrathecal amitriptyline act as an N-methyl-D-aspartate receptor antagonist in the presence of inflammatory hyperalgesia in rats?"
            ]
        },
        {
            "id": "task847-939f51f33c1d48bab131228e8d9549ef",
            "input": "Halothane exerts a potent negative inotropic effect on the heart and mimics many of the cardiac effects of lowered extracellular CaCl2. Reduced slow inward Ca2+ current and sarcoplasmic reticular effects on intracellular Ca2+ are likely involved. The authors reported previously that halothane protects against hypoxic and ischemia reperfusion injury in isolated hearts. The aim of this isolated heart study was to compare protective effects of halothane and low CaCl2 (0.5 mM) administered during 1 day of hypothermic perfusion on return of normothermic perfusion.', \"Guinea pig hearts (n = 66) were isolated and perfused at 37 degrees C with a Krebs' solution, gassed with 96% O2, 4% CO2, and containing 2.5 mM Ca2+, and 4.5 mM K+. Heart rate, isovolumetric left ventricular pressure, coronary flow, %O2 extraction, O2 consumption rate, and relative cardiac efficiency (EFF = heart rate.left ventricular pressure/O2 consumption rate) were measured in five groups of hearts: time controls (no hypothermia); 1.5, and 3% halothane delivered by vaporizer; cold controls (hypothermia only); and 0.5 mM CaCl2. Halothane was administered, or CaCl2 was decreased 0.5 h before hypothermia at 3.8 +/- 0.1 degrees C, during hypothermia for 22 h, and for 0.5 h after rewarming to 37.0 +/- 0.1 degrees C. Hearts were perfused at 25% of initial coronary flow during hypothermia.\", 'All groups had similar ventricular function and vasodilator responses before hypothermia. During normothermic reperfusion after hypothermia, both concentrations of halothane protected better than low CaCl2. Values, expressed as a percent of initial values in the five groups (time control, 3% halothane, 1.5% halothane, cold control, and 0.5 mM CaCl2, were respectively: 90 +/- 6, 54 +/- 6*, 48 +/- 5*, 27 +/- 8, 27 +/- 4% for left ventricular pressure; 84 +/- 5, 61 +/- 4*, 62 +/- 6*, 40 +/- 5, 34 +/- 5% for EFF; and 102 +/- 3, 63 +/- 3*, 66 +/- 3*, 55 +/- 2, 42 +/- 2% for coronary flow (*P < 0.05 halothane vs. 0.5 mM CaCl2). The coronary flow response to endothelium-dependent (acetylcholine) and endothelium-independent (nitroprusside) vasodilators was also greater after halothane than after 0.5 mM CaCl2.",
            "output": [
                "Does one-day hypothermic preservation of isolated hearts with halothane improve cardiac function better than low calcium?"
            ]
        },
        {
            "id": "task847-bc195f639a2f4ea1a7ad93601359850a",
            "input": "Volatile anesthetics exert cardioprotective effects during myocardial ischemia. This investigation examined the regional systolic and diastolic mechanical responses to brief left anterior descending coronary artery (LAD) occlusion in the central ischemic zone and in remote normal myocardium in the conscious state and during desflurane and isoflurane anesthesia.', 'Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, cardiac output, LAD coronary blood flow velocity, and LAD and left circumflex coronary artery subendocardial segment length. Regional myocardial contractility was evaluated with the slope of the preload recruitable stroke work relationship determined from a series of left ventricular pressure-segment length diagrams in the LAD and left circumflex coronary artery zones. Diastolic function was assessed with a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity in LAD and left circumflex coronary artery regions, and regional chamber stiffness constants derived using monoexponential and three-element exponential curve fitting in each zone. On separate experimental days, hemodynamics and indices of regional functional were obtained in the conscious state and during 1.1 and 1.6 minimum alveolar concentration end-tidal desflurane or isoflurane before and during LAD occlusion.', 'In conscious dogs, LAD occlusion abolished regional stroke work, increased chamber stiffness (monoexponential: 0.39 +/- 0.04 during control to 1.34 +/- 0.39 mm-1 during LAD occlusion), and decreased the rate of early ventricular filling in the ischemic zone. These changes were accompanied by increased contractility (slope: 103 +/- 8 during control to 112 +/- 7 mmHg during LAD occlusion), rapid filling rate (maximum segment lengthening velocity: 46 +/- 5 during control to 55 +/- 7 mm.s-1 during LAD occlusion), and chamber stiffness (monoexponential: 0.43 +/- 0.05 during control to 1.14 +/- 0.25 mm-1 during LAD occlusion) in the normal region. Increases in tau were also observed in the conscious state during the period of myocardial ischemia. Desflurane and isoflurane increased tau and decreased the slope and maximum segment lengthening velocity in a dose-related manner. Monoexponential and three-element element exponential curve fitting were unchanged by the volatile anesthetics in the absence of ischemia. Myocardial contractility and rapid filling rate were enhanced in the nonischemic region during LAD occlusion in the presence of desflurane and isoflurane. In contrast to the findings in the conscious state, ischemia-induced increases in tau and chamber stiffness in the ischemic and normal zones were attenuated during anesthesia induced by desflurane and isoflurane.",
            "output": [
                "Do desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs?"
            ]
        },
        {
            "id": "task847-acb59f74218647a19fb83b816b6810d0",
            "input": "Recent research suggests that body vitamin D levels are decreased in coronary heart disease and diabetes, but it is unclear which cardiovascular risk factors are related to vitamin D status.', 'To examine the relation between vitamin D status and major cardiovascular risk factors.', 'Serum 25-hydroxyvitamin D3, a marker of recent sun exposure and vitamin D status, was measured in 390 New Zealand residents (95 Pacific Islanders, 74 Maori and 221 others mostly of European descent), who were part of a larger cross-sectional survey of a workforce (n = 5677) aged 40-64 years.', 'Serum 25-hydroxyvitamin D3 levels were significantly lower in Pacific Islanders (mean (SE) = 56 (3) nmol/L; p = 0.0001) and Maoris (68 (3) nmol/L; p = 0.036) compared with Europeans (75 (2) nmol/L) after adjusting for age, sex and time of year. Also adjusting for ethnic group, 25-hydroxyvitamin D3 was higher in people doing vigorous (aerobic) leisure physical activities (71 (2) nmol/L; p = 0.0066) and moderate (non-aerobic) activities (68 (3) nmol/L; p = 0.12) compared with those who were inactive (63 (2) nmol/L). However, 25-hydroxyvitamin D3 was unrelated to body mass index, serum lipids, blood pressure or cigarette smoking.",
            "output": [
                "Is serum 25-hydroxyvitamin D3 related to physical activity and ethnicity but not obesity in a multicultural workforce?"
            ]
        },
        {
            "id": "task847-9074683fc8be49b49bc937d4145a6a60",
            "input": "Because accumulation of extracellular matrix is a prominent characteristic of the microangiopathy that complicates long-term diabetes, a pathogenetic role for transforming growth factor beta (TGF-beta) is being considered. Having observed that glucose levels mimicking diabetic hyperglycemia induce in vitro endothelial cell overexpression of extracellular matrix molecules, decreased replication, and increased levels of TGF-beta mRNA, we have examined whether the effects of high glucose are mediated by autocrine TGF-beta.', 'TGF-beta levels were measured by bioassay in the media conditioned by human umbilical vein endothelial cells cultured in the presence of high (30 mM) or normal (5 mM) glucose concentrations. The effect of high glucose was tested on the proliferation of two epithelial cell lines, one (Mv1Lu) exquisitely sensitive to TGF-beta and the other (DR mutants) insensitive to the cytokine. To examine whether high glucose and TGF-beta affect cellular programs in a similar manner, the effects of high glucose and exogenous TGF-beta were compared on proliferation and gene expression of endothelial cells.', 'Media conditioned by endothelial cells cultured in high or normal glucose contained similar amounts of TGF-beta (4.9 +/- 3.5 and 3.7 +/- 2.5 ng/10(6) cells, respectively (mean +/- SD)), all in the latent form. The replication of parental Mv1Lu cells and their DR mutants was decreased by high glucose to the same extent. Whereas the inhibitory effect of high glucose on endothelial cell replication was reversible, that of TGF-beta was not. Both perturbations induced up-regulation of fibronectin expression, but the effects were additive. Only TGF-beta induced overexpression of Type IV collagenase.",
            "output": [
                "Are the effects of high glucose on human endothelial cell growth and gene expression mediated by transforming growth factor-beta?"
            ]
        },
        {
            "id": "task847-65d3f430b31c4660bf7b9aa7e2e9c319",
            "input": "Type I hypersensitivity reactions caused by latex products are ascribed to proteins eluted from them, but little is known about the properties of these allergenic proteins. The reason for the cross-reaction between rubber latex and fruits is also not known. We have speculated that a series of defense-related proteins in plants is a cause of latex allergy and the cross reaction.', 'To verify our hypothesis, we selected a lysozyme as a representative defense-related protein and examined its relationship to latex allergy.', 'Lysozymes eluted from latex gloves were detected with a cell-suspension clearing test. A chromatographically separated lysozyme was investigated for its physicochemical and enzymatic properties and allergenicity.', 'Lysozyme activity was detected in extracts from ammoniated latex and latex gloves. We separated a lysozyme (27 kd; isoelectric point, 9.5) using cation-exchange and gel filtration chromatography. This lysozyme was enzymatically very similar to fruit lysozymes and was demonstrated to be an allergen.",
            "output": [
                "Is one of the rubber latex allergens a lysozyme?"
            ]
        },
        {
            "id": "task847-274e02d40e5f44e3983f7c3014ee2a51",
            "input": "Two years ago the authors began to use Swan-Ganz catheters to generate more complex hemodynamic data as a better guide to resuscitation of burns. This study uses the information to identify differences between survivors and nonsurvivors.', 'Fifty-three consecutive patients with major burns were treated using Swan-Ganz-generated data. Additional information was collected, including demographics, intake and output, medications, and arterial blood gas (including calculated oxygen consumption). Statistical analysis incorporated adjustments for autocorrelation.', 'The patients included 38 men and 15 women, averaged 43.7 years of age, and had a mean burn size of 40%. Thirteen patients suffered severe inhalation injury. Data collected hourly over 3 days were collapsed across 6-hour observation periods. Mean values, when plotted across time, discriminated the 37 survivors from the 16 nonsurvivors. Poor response to resuscitation as evidenced by increased use of colloid fluid and cardiotonic drugs plus failure to maximize oxygen consumption were associated with nonsurvival.",
            "output": [
                "Do survival in major burn injuries is predicted by early response to Swan-Ganz-guided resuscitation?"
            ]
        },
        {
            "id": "task847-d76e7a6f79d24348bd219d5c0f0002e5",
            "input": "Because severe acidosis is an indicator of poor prognosis in trauma patients, medical records of these patients were analyzed to determine whether aggressive resuscitation was appropriate.', 'Data from a level 1 trauma center registry were reviewed retrospectively to identify patients with a pH < or = 7.0. Thirty-seven patients were identified. Severely acidotic patients were compared to average trauma patients in terms of demographics, resuscitation, injury, and outcome. Surviving acidotic patients were also compared to nonsurviving acidotic patients.', 'Half of the severely acidotic group survived initial resuscitation with approximately one third surviving to leave the hospital. There were no chronically disabled survivors. Nonsurviving acidotic patients were more unstable, more neurologically depressed, and more severely injured. Resuscitation efforts did not consume excessive hospital resources.",
            "output": [
                "Does severe acidosis alone predict mortality in the trauma patient?"
            ]
        },
        {
            "id": "task847-76e2fedcfefd440d8ebf98641c0c9380",
            "input": "There is increasing interest in educational methods that are loosely aggregated under the title of problem-based learning (PBL), but it remains unclear whether PBL is as successful as its conventional predecessor in transmitting factual information.', \"The authors designed and implemented a PBL curriculum for a third-year surgical clerkship, then prospectively compared that technique with the conventional format. Each student's subject-related knowledge was assessed with a specifically tailored 195-question written exam and correlated with National Board of Medical Examiners shelf exams. Student and faculty responses to the technique were also sought and tabulated.\", 'Student and faculty responses to PBL were uniformly positive. We were unable, however, to demonstrate effects on our evaluation instruments. Neither individual student performance nor grouped scores differed based on the mode of presentation.",
            "output": [
                "Is problem orientation a new approach to surgical education?"
            ]
        },
        {
            "id": "task847-2b79185437984268938ece014dbf133f",
            "input": "Our objective was to study the direct effects of meconium on isolated umbilical artery and vein in vitro.', \"Intact umbilical artery and vein rings were suspended in 5 ml organ baths containing kreb's solution (pH 7.2, 37 degrees C; bubbled with 2.5% oxygen and 8.07% carbon dioxide, balance nitrogen) for isometric tension recording. Meconium alone (final bath concentration 1%), centrifuged and filtered meconium, and meconium with the lipid fraction removed (separated into < 30,000 kd and > 30,000 kd) were added to the baths. Some vessels were also incubated in 1% meconium for 30 minutes, after which the meconium was washed out. Concentration-response curves to U46619 were obtained. The negative log of the concentration that evokes 50% of the maximal contraction was determined.\", 'Umbilical artery and vein had no sustained response to meconium. Tension that developed by rings exposed to meconium was significantly less than control at all concentrations of U46619. There was some loss of the efficacy of meconium after centrifugation-filtration and washing out. Meconium without the lipid fraction had less inhibitory effect than did native meconium.",
            "output": [
                "Does meconium inhibit the contraction of umbilical vessels induced by the thromboxane A2 analog U46619?"
            ]
        },
        {
            "id": "task847-a5ed50fd81df4125976051c66228d3f4",
            "input": "Our purpose was to study the incidence and location of histologic evidence of intrauterine bleeding in preterm and term placentas.', \"A total of 462 consecutive placentas delivered at < 32 weeks' gestation, from which cases of placenta previa, stillbirth, and multiple gestation were excluded, were compared with 108 consecutive term placentas (with similar exclusion criteria) in regard to the presence of hemosiderin in decidua of basal plate or placental membranes. Of the 462 preterm cases, 448 charts made specific reference to the presence or absence of vaginal bleeding. Bloody show alone was not considered bleeding. The blinded scoring of lesions (including acute ascending infection, uteroplacental vascular pathologic processes and related ischemic damage, chronic inflammation, and coagulation related lesions) was analyzed by contingency tables (p < 0.05 significant).\", 'A total of 196 of 462 (43%) preterm placentas had any decidual hemosiderin compared with one of 108 (0.8%) at term (p < 0.00001). Among the preterm cases, hemosiderin was significantly more common in preeclampsia (45/76, 60%) and in cases clinically diagnosed as nonhypertensive abruptio placentae (21/33, 64%) than in premature membrane rupture (72/192, 37.5%) and preterm labor (58/161, 36%, p < 0.003). The incidence of placental lesions in preterm cases with extraplacental membrane hemosiderin was not different than it was in cases without hemosiderin. Placental lesions related to basal-plate decidual hemosiderin in the preterm cases were villous infarct (p < 0.0001), uteroplacental vessels with absence of physiologic change (p < 0.003) and increased numbers of circulating nucleated erythrocytes (p < 0.0007), uteroplacental thrombosis (p < 0.0001), and villous fibrosis (p < 0.0001) and hypovascularity (p < 0.0001). Among the preterm cases, 23 of 48 (48%) with first-trimester bleeding, 33 of 66 (50%) with second-trimester bleeding, and 31 of 64 (48%) with multiple episodes of bleeding had decidual hemosiderin (p < 0.0001). A clinical history of gestational bleeding was significantly less common in cases of preterm preeclampsia with histologic evidence of bleeding (four of 73, 5.5%) than in nonhypertensive abruptio placentae (18/31, 58%), premature rupture of membranes (52/183, 28%), or preterm labor (31/161, 19%, p < 0.0001). Hemosiderin was not related to clinical bleeding < 72 hours of delivery (p > 0.20).",
            "output": [
                "Is histologic evidence of old intrauterine bleeding more frequent in prematurity?"
            ]
        },
        {
            "id": "task847-720b4f5f4fc24b22b98c02fa589bb223",
            "input": "Energy needs in infants are decreased after surgery because of growth inhibition (resulting from catabolic stress metabolism), decreased insensible losses, and inactivity. Using standardized formulas that account for growth, activity, and insensible losses during this stress period can lead to overfeeding in excess of 200% of the actual measured requirement. Overfeeding during this acute injury period can result in increased CO2 production from lipogenesis. This study determined the effects of a reduced rate of mixed caloric repletion on infant energy use during the early postoperative period.', 'C-reactive protein (CRP), oxygen consumption (VO2), carbon dioxide production (VCO2), measured energy expenditure (MEE), and total urinary nitrogen (TUN) were measured serially in seven infants (average age, 78 days) during the first 72 hours after abdominal or thoracic surgery. Nonprotein respiratory quotient (RQnp), and values for oxidation of carbohydrate (Ce) and fat (Fe) were calculated. Injury severity was stratified based on serum CRP concentrations of > or = 6.0 mg/dL (high stress) or < 6.0 mg/dL (low stress). Recovery from acute stress was analyzed by comparing studies in which CRP had decreased to < or = 2.0 mg/dL (resolving stress group) with those in which CRP values were greater than 2.0 mg/dL (acute stress group).', 'Average total caloric intake (64.56 +/- 18.51 kcal/kg/d; approximately 50% of predicted energy requirement) exceeded average MEE (42.90 +/- 9.98 kcal/kg/d) by approximately 50%. Average TUN was 0.18 +/- 0.07 g/kg/d (high stress 0.2 +/- 0.05 versus low stress 0.16 +/- 0.09 g/kg/d). Average RQnp was 1.05 +/- 0.13 and average Ce was 37.28 +/- 16.86 kcal/kg/d. The average calculated Fe was 0.0 +/- 12.27 kcal/kg/d, reflecting approximately equal amounts of fat oxidized compared with fat generated from excess glucose (lipogenesis). When individual studies were analyzed at a CRP cutpoint of 2.0 mg/dL, overfeeding (RQ > 1.0) was significantly less likely in the resolving (2/6 studies, 33.4%) versus acute stress (9/13 studies, 69.2%, Z test P < .001) group. Five of seven (5/7) patients (9/19 individual studies) had negative Fe values (average -9.89 +/- 10.02) reflecting net lipogenesis. The RQnp for these nine studies was 1.14 +/- 0.11 versus 0.97 +/- 0.09 for the remaining 10, and this difference was significant (P < .01). A significant correlation existed between carbohydrate intake and VCO2 (Pearson r = .6951, P < .01). In addition, there was a good correlation between carbohydrate intake and VCO2 (Pearson r = .6591, P < .01). The coefficient of variation for MEE was 8.0% (low stress) versus 30.2% (high stress).",
            "output": [
                "Do early postoperative alterations in infant energy use increase the risk of overfeeding?"
            ]
        },
        {
            "id": "task847-ba29e3a501c448d889593f3b35ceb6ed",
            "input": "Animal models for hepatic metastases can facilitate the investigation of lymphokine-activated killer (LAK) cell-based immunotherapy. The aim of this study was to investigate the efficacy of ccM4 antibody-targeted LAK cells in inhibiting hepatic micrometastases.', 'Hepatic micrometastases were generated after the intrasplenic injection of HM7 colon carcinoma cells. TAG72 expression was detected in these hepatic micrometastases using ccM4 antibody. The ccM4 antibody was conjugated onto LAK cells by treatment with 17.5% polyethylene glycol 8000. After the intrasplenic injection of HM7 cells, severe combined immunodeficient mice were randomized into five groups (i-v) and received either 10(7) ccM4-LAK cells plus 1000 U interleukin 2 (IL-2; group i), LAK cells plus 50 micrograms ccM4 and IL-2 (group ii), LAK cells plus IL-2 (group iii), IL-2 alone (group iv), or only phosphate-buffered saline (group v).', 'The ccM4-LAK cells retained cytolytic activity and acquired TAG72-binding reactivity. The results showed that group i had significantly fewer hepatic metastases compared with group ii or group iii (P < 0.05) and even fewer hepatic metastases compared with group iv or group v (P < 0.001).",
            "output": [
                "Do antibody-targeted lymphokine-activated killer cells inhibit liver micrometastases in severe combined immunodeficient mice?"
            ]
        },
        {
            "id": "task847-6a2aaf271391493c83d82c4163aca097",
            "input": "Nitric oxide is now recognized to regulate immune responses and cell viability in various organs. The present study was designed to clarify whether NO released from Kupffer cells modulates the lymphokine-activated killer (LAK) activity of interleukin 2 (IL-2)-treated splenocytes.', 'Splenocytes and Kupffer cells were isolated from male Wistar rats and cocultured for 48 hours in the presence of lipopolysaccharide (1 microgram/mL). The splenocyte LAK activity and expression of IL-2 receptor were determined.', \"Kupffer cells with lipopolysaccharide reduced the IL-2 receptor expression and LAK activity of splenocytes. The addition of either NG-monomethyl-L-arginine, an inhibitor of NO synthesis, or aminoguanidine, an inhibitor of inducible NO synthase, to the medium reversed the suppression of IL-2 receptor expression and LAK activity by lipopolysaccharide-stimulated Kupffer cells. 8-bromoguanosine 3',5'-cyclic monophosphate and NO donors decreased the splenocyte LAK activity and IL-2 receptor expression. Treatment with lipopolysaccharide increased the inducible NO synthase activity as well as the nitrite and nitrate levels in the culture medium of Kupffer cells but not in splenocytes.",
            "output": [
                "Does rat Kupffer cell-derived nitric oxide modulate induction of lymphokine-activated killer cell?"
            ]
        },
        {
            "id": "task847-0ce0f44ddc0e493ba528a5100ab2fff3",
            "input": "The effect of nutrients in the distal small intestine or colon on postprandial upper gut function is incompletely understood. The aim of this study was to determine if carbohydrate in the ileum or proximal colon of dogs affects postprandial pancreaticobiliary secretion, gastrointestinal transit, and circulating concentrations of certain gastrointestinal regulatory peptides.', 'Seven dogs were prepared with permanent infusion and aspiration catheters in the duodenum and ileum and an infusion catheter in the cecum. Coincident with eating a meal containing liquid and solid markers, ileal or colonic (n = 5 dogs for each) infusion were begun of isosmolar 0.9% NaCl or carbohydrate in a 3:1 ratio of starch to glucose. Pancreatic enzyme output, bile acid delivery, gastrointestinal polypeptide, and plasma concentrations of pancreatic polypeptide, neurotensin, and peptide YY were measured for 6 hours postprandially.', 'Carbohydrate infusion in the ileum, but not in the proximal colon, increased amylase secretion and plasma peptide YY, slowed gastric emptying of liquids and solids, slowed small intestinal transit, and decreased bile acid delivery into the duodenum (P < 0.05 in each).",
            "output": [
                "Does intraileal carbohydrate regulate canine postprandial pancreaticobiliary secretion and upper gut motility?"
            ]
        },
        {
            "id": "task847-35abc1abd9b54b4197afd132a8e3cabf",
            "input": "To examine the hypothesis that induction of heat shock proteins in human endothelial cells (ECs) by either heat shock or sodium arsenite could prevent subsequent EC necrosis induced by activated human polymorphonuclear neutrophil leukocytes (PMNs).', 'Cultures of ECs were exposed to heat shock (42 degrees C, 30 to 60 minutes) or sodium arsenite (40 to 320 mumol/L) for 6 hours to induce the expression of a heat shock protein of 72-kd molecular weight (HSP-72). Activated PMNs were subsequently added to these ECs for 24 hours to evaluate the ability of HSP-72 to prevent activated PMN-mediated EC necrosis.', 'Neither EC necrosis nor apoptosis was induced by heat shock. Sodium arsenite (40 to 80 mumol/L) did not induce EC necrosis, although 320-mumol/L sodium arsenite caused a significant increase in EC necrosis. Sodium arsenite (80 to 320 mumol/L) also induced dose-dependent EC apoptosis. Endothelial cells exposed to heat shock and sodium arsenite (40 and 80 mumol/L) significantly attenuated subsequent EC necrosis induced by activated PMNs. However, sodium arsenite at 320 mumol/L aggravated activated PMN-mediated EC necrosis. Expression of HSP-72 was detected after ECs were treated both with heat shock and sodium arsenite (40 to 320 mumol/L) for 6 hours.",
            "output": [
                "Does induction of heat shock protein 72 prevent neutrophil-mediated human endothelial cell necrosis?"
            ]
        },
        {
            "id": "task847-8a01d15db6e14b4fa142a6d3beac7f75",
            "input": "To determine the effects of polymyxin B sulfate in rats fed by total parenteral nutrition on norepinephrine excretion, macrophage tumor necrosis factor production, and bacterial translocation.', 'Randomized animal study.', 'A university teaching hospital in Seattle, Wash.', 'Three groups of rats were studied: chow plus intravenous saline, total parenteral nutrition, or total parenteral nutrition supplemented with polymyxin B sulfate. After 5 days, urinary excretion of norepinephrine and epinephrine was calculated, peritoneal and alveolar macrophages were cultured, and their spontaneous and lipopolysaccharide-stimulated tumor necrosis factor production was measured. Mesenteric lymph nodes were cultured for bacteria.', 'Rats fed by total parenteral nutrition had increased urine norepinephrine excretion (33%) and alveolar macrophage tumor necrosis factor production (80%) and trends for increased epinephrine excretion and bacterial translocation compared with rats fed chow. Alveolar but not peritoneal macrophage tumor necrosis factor production was significantly related to norepinephrine excretion (r = .5, P < .01). The addition of polymyxin B to total parenteral nutrition decreased weight gain (P < .05), urinary norepinephrine excretion (P < .01), and alveolar macrophage tumor necrosis factor production (P < .05) compared with rats fed by total parenteral nutrition. Polymyxin B also tended to decrease the magnitude of bacterial translocation.",
            "output": [
                "Does polymyxin B prevent increased sympathetic activity and alveolar macrophage tumor necrosis factor release in parenterally fed rats?"
            ]
        },
        {
            "id": "task847-a5f95fa2f492422f8110e17bb57b243d",
            "input": "Age and certain pathologic features (ie, follicular histology, vascular invasion, and extracapsular extension) are reported to impact on prognosis in thyroid cancer, but the relationship between these two factors remains incompletely defined.', 'Clinical, pathologic, therapeutic, prognostic, and outcome data were retrospectively collected and compared among three groups of patients with thyroid cancer: group 1 (age 21 to 50), group 2 (age 51 to 70), and group 3 (age greater than 70).', 'There was a statistically significant age-related decrement in survival: 10-year survival was 92% in group 1, 77% in group 2, and 48% in group 3. Follicular histology, vascular invasion, and extracapsular extension were more frequently observed in group 3 versus group 2 and in group 2 versus group 1 (all differences statistically significant except for vascular invasion). Although survival was significantly less for group 3 versus group 2 versus group 1, only vascular invasion and extracapsular extension independently predicted outcome by multivariate analysis.",
            "output": [
                "Does age correlate with increased frequency of high risk factors in elderly patients with thyroid cancer?"
            ]
        },
        {
            "id": "task847-d184c8e4ac7c4ba9909e8fafbbdbe6fa",
            "input": "Locally advanced colorectal cancer often requires extended resection to radically remove all tumor. This is the only chance for cure in these patients, but a higher complication rate would be expected. To evaluate the overall benefit for the patient, this study assesses morbidity and mortality as well as long-term survival of patients who underwent extended resection for a T3-T4 carcinoma.', 'Two hundred twenty patients with locally advanced adenocarcinoma of the colorectum were included. One hundred fifty presented with a T3 and 70 with a T4 tumor. Eighty-three patients underwent extended resection. In 38 patients extended en bloc resection was performed because of inflammatory adherence mimicking infiltration. Thirty-three patients who underwent extended resections were over 70 years of age. There were no significant differences between the groups that underwent extended or nonextended resections in age, sex, stage, or grading.', 'pT4 lesions were significantly more frequent in the extended resection group than in the nonextended resection group. Mean survival was 44 months after extended resections and 45 months after nonextended resections. In the extended resection group there was no significant difference in mean survival between pT3 and pT4 stage patients within 46 and 38 months, respectively. In patients who underwent nonextended resections, however, there was a significant difference in mean survival within 48 months for pT3 and 28 for pT4 patients (P < 0.05). Postoperative morbidity and mortality were comparable between the extended resection group and the non-extended resection group. The presence of residual tumor influenced prognosis of patients significantly; R0 resections fared significantly better than patients who underwent R1 or R2 resections (55 and 51 to 14/12 and 23/8 months) (P < 0.01). Nodal stage and International Union Against Cancer stage were also significant determinants of prognosis. After extended resections mean survival morbidity and 30-day mortality in patients more than 70 years was similar to those less than 70 years.",
            "output": [
                "Are extended resections beneficial for patients with locally advanced colorectal cancer?"
            ]
        },
        {
            "id": "task847-9a3d7a40bc2e44ae94e08228627ae76b",
            "input": "Expression of disaccharidase sucrase-isomaltase (SI) is significantly enhanced during neoplastic transformation of colonic epithelium. Our study was designed to determine whether expression of SI within primary tumors was significantly associated with survival in patients with colorectal carcinoma (CRC).', 'SI expression was analyzed by immunohistochemistry in paraffin sections from 182 Stage I to III CRC that had been resected for cure at the New England Deaconess Hospital between 1965 and 1977. Expression was scored as absent or present in 1 to 50 percent or more than 50 percent of tumor cells. Associations were explored among SI expression, other clinical or pathologic variables, and overall survival. The data set is mature, with 91 (56 percent) patients who had died of CRC at a median follow-up of 96 months.', 'Fifty-five percent of primary CRC expressed SI. When the multivariate Cox analysis was performed, nodal status, T stage, primary site, grade, and SI expression were independent covariates. SI expression was not associated with the expression of other clinicopathologic variables but increased the risk of death from colorectal carcinoma by 1.83-fold.",
            "output": [
                "Is sucrase-isomaltase an independent prognostic marker for colorectal carcinoma?"
            ]
        },
        {
            "id": "task847-ce7349cdcc3949f6954ef85605bc691d",
            "input": "Despite the growth of managed care in the United States, there is little information about the arrangements managed-care plans make with physicians.', 'In 1994 we surveyed by telephone 138 managed-care plans that were selected from 20 metropolitan areas nationwide. Of the 108 plans that responded, 29 were group-model or staff-model health maintenance organizations (HMOs), 50 were network or independent-practice-association (IPA) HMOs, and 29 were preferred-provider organizations (PPOs).', \"Respondents from all three types of plan said they emphasized careful selection of physicians, although the group or staff HMOs tended to have more demanding requirements, such as board certification or eligibility. Sixty-one percent of the plans responded that physicians' previous patterns of costs or utilization of resources had little influence on their selection; 26 percent said these factors had a moderate influence; and 13 percent said they had a large influence. Some risk sharing with physicians was typical in the HMOs but rare in the PPOs. Fifty-six percent of the network or IPA HMOs used capitation as the predominant method of paying primary care physicians, as compared with 34 percent of the group or staff HMOs and 7 percent of the PPOs. More than half the HMOs reported adjusting payments according to utilization or cost patterns, patient complaints, and measures of the quality of care. Ninety-two percent of the network or IPA HMOs and 61 percent of the group or staff HMOs required their patients to select a primary care physician, who was responsible for most referrals to specialists. About three quarters of the HMOs and 31 percent of the PPOs reported using studies of the outcomes of medical care as part of their quality-improvement programs.",
            "output": [
                "Do a national survey of the arrangements managed-care plans make with physicians?"
            ]
        },
        {
            "id": "task847-e826bb69017a4cd4bed6facbfbf2895b",
            "input": "Gastric lipase is an important enzyme for dietary triglyceride digestion in normal subjects. Its regulation is unknown, as is the relation between the quantity and activity of the enzyme.', 'In a dose-response study we investigated the effect of low doses of pentagastrin (less than 1000 ng/kg/h) on the output of gastric lipase measured by a kinetic assay and an enzyme-linked immunosorbent assay (ELISA).', 'In five healthy volunteers stepwise intravenous pentagastrin infusions of 0, 50, 100, 500, and 1000 ng/kg/h resulted in a stepwise increase in the lipase output, as measured with ELISA. However, the lipolytic activity, measured with a kinetic assay, decreased as the pH of the gastric contents decreased.",
            "output": [
                "Do low doses of pentagastrin stimulate gastric lipase secretion in man?"
            ]
        },
        {
            "id": "task847-fb0d668e67794526a1181d5aa4f7fe5e",
            "input": "Helicobacter pylori infection is now accepted as the most common cause of chronic active gastritis and peptic ulcer disease. The etiologies of many infectious diseases have been attributed to specific or clonal strains of bacterial pathogens. Polymerase chain reaction (PCR) amplification of DNA between repetitive DNA sequences, REP elements (REP-PCR), has been utilized to generate DNA fingerprints to examine similarity among strains within a bacterial species.', 'Genomic DNA from H. pylori isolates obtained from 70 individuals (39 duodenal ulcers and 31 simple gastritis) was PCR-amplified using consensus probes to repetitive DNA elements. The H. pylori DNA fingerprints were analyzed for similarity and correlated with disease presentation using the NTSYS-pc computer program.', 'Each H. pylori strain had a distinct DNA fingerprint except for two pairs. Single-colony DNA fingerprints of H. pylori from the same patient were identical, suggesting that each patient harbors a single strain. Computer-assisted cluster analysis of the REP-PCR DNA fingerprints showed two large clusters of isolates, one associated with simple gastritis and the other with duodenal ulcer disease.",
            "output": [
                "Does cluster analysis of Helicobacter pylori genomic DNA fingerprints suggest gastroduodenal disease-specific associations?"
            ]
        },
        {
            "id": "task847-17c73fd435c94feeaf9acec4faa03f44",
            "input": "To study the effect of interleukin-1 (IL-1) on the synthesis of proteoglycans biglycan (DSPG-I) and decorin (DSPG-II) in intact bovine articular cartilage.', 'Cartilage bearing sesamoid bones from the metacarpophalangeal joint were cultured with 10 ng/ml IL-1 for 2 days and labelled with [35S] sulfate. One sesamoid bone from each animal had been labelled ex vivo. The remaining 2 were cultured with IL-1 and allowed to recover in control medium before labelling. Control cultures were maintained in medium without IL-1 and labelled concurrently with the experimental series. The dermatan sulfate proteoglycans were purified from 4 M guanidinium chloride extracts of the cartilage by gel filtration on Sepharose CL-2B and CL-4B, on which they appeared as a single peak. Biglycan and decorin were separated by sodium dodecyl sulfide polyacrylamide gel electrophoresis in high salt. Individual lanes from the gel were cut in slices, which were dissolved and counted for radioactivity.', 'Ex vivo, biglycan accounted for 4% and decorin for 2% of total incorporated sulfate. IL-1 reduced the synthesis of biglycan to 77% of the level of cultured controls and that of decorin to 73%. The synthesis of both proteoglycans returned to the control levels when the IL-1 was removed. IL-1 (10 ng/ml, 2 days) had no significant effect on total proteoglycan synthesis.",
            "output": [
                "Does interleukin-1 reversibly inhibit the synthesis of biglycan and decorin in intact articular cartilage in culture?"
            ]
        },
        {
            "id": "task847-03992b9839844d29880f2a48258784f6",
            "input": "To determine the effect of infusion with a dual-binding antibody to E- and L-selectin, EL-246, in a postonset model of sepsis.', 'Nonrandomized controlled study.', 'Young Yorkshire swine.', 'Three groups were studied. Controls (n = 8) received saline solution only. Untreated animals with sepsis (n = 8) received a 1-hour intravenous infusion of live Pseudomonas aeruginosa. Animals treated with EL-246 (n = 6) received the same bacterial infusion and a 2-mg/kg bolus of EL-246 at 30 minutes.', 'Systemic and pulmonary hemodynamics, arterial blood gas determination, bronchoalveolar lavage protein and neutrophil content, neutrophil integrin and selectin expression, neutrophil oxidant burst, and organ myeloperoxidase content.', 'Treatment with EL-246 significantly reduced lung injury, as indicated by improved bronchoalveolar lavage protein and neutrophil content, resulting in a significant improvement in arterial oxygenation. This reduction in lung injury was produced by a reduction in lung myeloperoxidase content. Treatment with EL-246 failed to prevent the development of pulmonary hypertension and systemic hypotension. Neutrophils from animals with sepsis exhibited significant activation and upregulation of CD18, shedding of L-selectin, and production of increased levels of oxidants compared with controls.",
            "output": [
                "Is sepsis-induced acute lung injury attenuated by selectin blockade following the onset of sepsis?"
            ]
        },
        {
            "id": "task847-37482adc61e948a0b0925ae6f61fcf8b",
            "input": "Trauma is believed to activate immunocytes but paradoxically also increases the risk of intraperitoneal infection.', 'To investigate these events by evaluating changes in the cytokine control networks of human peritoneal macrophages (PM phi) early after trauma.', 'Case-control study comparing cytokine messenger RNA (mRNA) expression by PM phi from patients with extra-abdominal trauma with that of both peripheral blood mononuclear cells (PBM) and PM phi obtained from healthy individuals.', 'Level I trauma center and basic science laboratory in a university hospital center.', 'Six patients with polytrauma (Injury Severity Score, > or = 15) with clinically negative diagnostic peritoneal lavages performed on routine indications at admission to the emergency department and six healthy age- and sex-matched individuals undergoing inguinal herniorrhaphy under local anesthesia.', 'Peritoneal macrophages were isolated from diagnostic peritoneal lavages in trauma patients. Identical lavages were performed through the hernia sac in the control group.', 'Cellular RNA was assayed for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta, IL-6, and IL-10 message by semiquantitative reverse-transcription polymerase chain reaction.', 'Normal PM phi expressed high levels of TNF-alpha mRNA relative to PBM, but expression of the other proinflammatory cytokines was equivalent to that of PBM. Peritoneal macrophage expression of TNF-alpha mRNA was markedly (64-fold) decreased after trauma (P < .001), when PBM expression of IL-10 mRNA was increased (P = .03).",
            "output": [
                "Is tumor necrosis factor alpha gene expression in human peritoneal macrophages suppressed by extra-abdominal trauma?"
            ]
        },
        {
            "id": "task847-cee7376cfe8e4f4e85148e90c79d2204",
            "input": "Haemophilus species are a common cause of community-acquired pneumonia; however, their significance in posttraumatic pneumonia is unclear.', 'Case series.', 'University hospital, level I trauma center.', 'Two hundred fifty-seven consecutive patients with blunt and penetrating trauma treated for pneumonia.', 'Length of stay in the intensive care unit, duration of ventilatory support, rate of recurrent or persistent pneumonia, and mortality.', 'Ninety-six (37%) of 257 patients treated for pneumonia had a Haemophilus species isolated on sputum culture. Of these 96 patients, 49 (51%) had only Haemophilus species, while 33 (34%) had associated gram-positive organisms and 14 (15%) had gram-negative organisms. Seventeen pure cultures (29%) and seven mixed cultures (15%) (P < .05) were beta-lactamase-positive trains. Compared with patients who had pneumonia caused by other bacteria, patients with Haemophilus species were younger (mean +/- SE, 35 +/- 1.7 vs 42 +/- 1.6 years; P < .05) and more severely injured (Injury Severity Score, 20.7 +/- 1.1 vs 17.5 +/- 0.9; P < .05). There were no differences in any outcome variables between the two groups. Only one (1%) of 96 patients had persistent Haemophilus species on sputum cultures after 7 days of treatment.",
            "output": [
                "Is haemophilus pneumonia a common cause of early pulmonary dysfunction following trauma?"
            ]
        },
        {
            "id": "task847-5710da9a191b49b4afa48db9132e9b6a",
            "input": "Leprosy represents a spectrum of clinical manifestations that reflect the immune response to antigens of Mycobacterium leprae. The tuberculoid form of leprosy, which is characterized by an organized development of granulomas, has recently been correlated with a Th1-like immune response. The lepromatous form of leprosy, with a characteristic lack of cellular immunity, has been correlated with a Th2-like immune response to mycobacterial antigens. Dipeptidylpeptidase IV (CD26) is an ectopeptidase that is expressed in various tissues; in the hemopoietic system, it is predominantly expressed by T cells.', \"We stained frozen sections of skin biopsies obtained from patients with different forms of leprosy, sarcoidosis, and Piringer's lymphadenitis. Sections were stained for interferon-gamma (IFN-gamma) and CD26 with the alkaline phosphatase anti-alkaline phosphatase technique and in two-color stainings by immunofluorescence.\", \"We found strong signals for IFN-gamma and for CD26 in all investigated cases of tuberculoid leprosy. In contrast, in all biopsies taken from patients with lepromatous leprosy, we found no or very weak signals for these antigens. By immunofluorescence double-labeling, we could show that IFN-gamma and CD26 were expressed by the identical cell population. We confirmed this correlation of CD26 expression and IFN-gamma production in other granulomatous inflammatory reactions such as sarcoidosis and Piringer's lymphadenitis.",
            "output": [
                "Does cD26 expression in leprosy and other granulomatous diseases correlate with the production of interferon-gamma?"
            ]
        },
        {
            "id": "task847-795b3b59ce5b42bfb5e39f2898daa556",
            "input": "The yeast Hansenula anomala has been associated with gastrointestinal symptomatology and damage to the intestinal wall in humans. In vitro and in vivo, H. anomala secretes a toxin, killer toxin, which is lethal to other microorganisms. In view of the very high rate of killer phenotype expression recorded for H. anomala strains in nature, this study aimed to investigate the hypothesis that H. anomala killer toxin plays a role in the pathogenesis of H. anomala-induced enteritis.', 'Effects of active and heat-inactivated H. anomala killer toxin on intestinal fluid homeostasis and electrolyte balance were investigated in rat small intestine using a standard intestinal perfusion technique. Sections of the perfused jejunum tracts were examined histologically.', 'H. anomala killer toxin induced a significant secretion of water and electrolytes. No significant change was observed when either heat-inactivated H. anomala killer toxin or control growth medium were tested. Histological analysis showed ischemic degeneration of villi and sloughing of surface epithelium in 50% of active H. anomala killer toxin-perfused jejuna.",
            "output": [
                "Does hansenula anomala killer toxin induce secretion and severe acute injury in the rat intestine?"
            ]
        },
        {
            "id": "task847-22b3b723f65e47daa3cb47ba17ae24f4",
            "input": "Effective material exchange between blood and tissue depends on the heterogeneity of microvascular flow. The objective was to address inconsistencies between intravital studies regarding this dependency. We tested the hypothesis that heterogeneity of red blood cell velocity (VRBC) in capillary beds varies with the strength of metabolic stimulus and with capillary bed geometry.', 'We used videomicroscopy to measure VRBC in a bed of 10-24 capillaries at the surface of extensor digitorum longus (EDL) muscle in anesthetized rats. The coefficient of variation (CV = standard deviation/mean; an index of spatial heterogeneity) was computed in the same bed before and after (i) 1, 2, 4, or 8 Hz supramaximal muscle contraction or (ii) adenosine superfusion (10(-7)-10(-3) M). Beds with or without arteriolar-venular capillary shunts were used.', 'Although control VRBC differed between beds (shunt: 232 microns/s; no shunt: 130 microns/s), the percentage increases in postcontraction VRBC did not (range: 111-326%). In both beds, control CV varied greatly (overall range: 28-117%) and 2-8 Hz muscle contractions reduced CV significantly by 25%. Similar results were obtained for adenosine. In confirmatory experiments using the rat cremaster muscle, contractions (4 Hz) and adenosine (10(-4) M) also reduced CV. Based on all data, CV = 63-0.022 VRBC (r = 0.82, P < 0.001).",
            "output": [
                "Does heterogeneity of red blood cell velocity in skeletal muscle decrease with increased flow?"
            ]
        },
        {
            "id": "task847-188215e6361a4b15a28155acc459e3e8",
            "input": "Considering the hypothesis that androgen-independent but growth factor dependent epithelial cell division may be important in the development and progression of prostate cancer and that protein tyrosine kinases and phosphotyrosine protein phosphatases are key enzymes modulating the levels of specific phosphotyrosylated proteins implicated in several growth factor regulated signal transduction pathways, our aim was to study the cellular distribution of phosphotyrosine proteins in normal and hyperplastic dog prostates as well as in those of castrated dogs supplemented with either androgens or estrogens in order to modify the relative proportion of basal versus secretory epithelial cells.', 'Following the determination of optimal conditions to specifically detect phosphotyrosine proteins by a rabbit polyclonal antibody directed against phosphotyrosine, immunohistochemistry was performed on prostate tissue sections from these experimental animals. In addition to morphological criteria, an antibody to high molecular weight cytokeratins and antisera against arginine esterase were used to selectively identify basal and secretory cells. Since prostatic acid phosphatase may be involved in the local regulation of phosphotyrosine proteins, its distribution was also evaluated with a human prostatic acid phosphatase antiserum.', 'In all prostatic tissues examined, basal epithelial cells were preferentially and specifically stained with antiphosphotyrosine. The staining intensity per basal cell was highest in the estrogen-supplemented dogs. In addition, basal cells were numerically increased and all were highly immunoreactive for high molecular weight cytokeratins. In prostates displaying a well-differentiated glandular epithelium, the number of positive basal cells and their staining intensity varied in the following order: normal < hyperplastic < androgen-supplemented dogs. At all times, the levels of phosphotyrosine proteins in prostatic acid phosphatase and arginine esterase positive cells (secretory) remained low. Fibroblasts and smooth muscle cells were unreactive to antiphosphotyrosine, even though estrogen supplementation increased the prostatic stromal volume.",
            "output": [
                "Do phosphotyrosine antibodies preferentially react with basal epithelial cells in the dog prostate?"
            ]
        },
        {
            "id": "task847-2bbe860f41c946ec9beb90b9218b35e6",
            "input": "The goal of this investigation was to examine the effect of immunity to nerve growth factor (NGF) on alterations in sensory nerves from the urinary bladder in the dorsal root ganglia (DRG) and their projections to the L6/S1 spinal cord following urethral obstruction in the rat.', 'Female Wistar rats were immunized to murine 2.5S NGF, then obstructed by partial urethral ligation for 6 weeks. Retrograde axonal tracing with FluoroGold and WGA-HRP was used to measure areas of bladder DRG cells and afferent projections in the sacral spinal cord. Multiunit activity on bladder nerves allowed recording of micturition reflexes. Immunohistochemical staining for growth associated protein (GAP)-43 in the sacral parasympathetic nucleus (SPN) was used to assess potential growth or activity of axons in the spinal cord. Voiding frequencies were then measured in awake obstructed and NGF immune-obstructed rats.', 'Immunity to NGF prevented obstruction-induced hypertrophy of DRG neurons, reduced retrograde axonal labeling of sacral afferent projections, eliminated enhancement of a spinal micturition reflex and abolished the increased GAP-43 expression in the SPN. Immunity to NGF prevented the urinary frequency that accompanies obstruction.",
            "output": [
                "Does immunity to nerve growth factor prevent afferent plasticity following urinary bladder hypertrophy?"
            ]
        },
        {
            "id": "task847-e649c0aaf9c143c488bb4c6b734cec73",
            "input": "To determine the activity of the calcium-dependent constitutive (cNOS) and calcium-independent inducible nitric oxide (iNOS) synthases in heart tissue from patients with different cardiac diseases.', 'Endomyocardial biopsy specimens were obtained from patients with dilated hearts (by echocardiography and ventriculography) and normal coronary arteries (by selective angiography). Recognised clinical, radiological, and histopathological criteria were used to diagnose non-inflammatory dilated cardiomyopathy (DCM) (n = 6), inflammatory cardiomyopathy (ICM) (n = 5), and peripartum cardiomyopathy (PPCM) (n = 3). Comparative groups were chosen with similarly dilated hearts caused by ischaemic (n = 5) or valvar disease (n = 4), and, in addition, non-dilated hearts with ischaemic (n = 5) and valvar (n = 3) disease. Venous blood was taken at the time of myocardial biopsy for assay of plasma tumour necrosis factor alpha (TNF alpha).', 'Myocardial tissue from patients with DCM, ICM, and PPCM showed considerable iNOS activity (16.8 (2.7) pmol citrulline/mg protein/min) with little or no cNOS activity (1.3 (0.9) pmol citrulline/mg protein/min). In contrast, myocardial tissue from patients with both dilated and non-dilated hearts of ischaemic or valvar aetiology showed cNOS and little, if any, iNOS activity (dilated--cNOS 11.7 (2.4) and iNOS 0.8 (0.6) pmol citrulline/mg protein/min; non-dilated--cNOS 12.1 (1.8) and iNOS 1.4 (0.8) pmol citrulline/mg protein/min). Plasma TNF alpha was detectable only in patients with inflammatory DCM.",
            "output": [
                "Is myocardial calcium-independent nitric oxide synthase activity present in dilated cardiomyopathy , myocarditis , and postpartum cardiomyopathy but not in ischaemic or valvar heart disease?"
            ]
        },
        {
            "id": "task847-548ba338cd1e40dc9a64d9ef29169abb",
            "input": "Hemodilution lowers the total circulatory red cell mass and blood viscosity and thereby may alter the time of passage of red cells and plasma through cerebral microvessels. This study was designed to clarify this question.', 'Adult Wistar-Kyoto rats, aged approximately 32 weeks, were divided into hemodilution and control groups. Local cerebral blood flow and microvascular red cell and plasma volumes in 14 brain structures were measured with the use of [14C]iodoantipyrine, 55Fe-labeled red cells, and [14C]inulin, respectively.', 'In the control group, the hematocrit in cerebral microvessels ranged from 0.29 to 0.45 with a mean of 0.36, which was 71% of the systemic hematocrit (0.51). The mean transit times of blood, red cells, and plasma through microvessels were 0.62 to 1.77 seconds (mean, 0.92 second), 0.44 to 1.15 seconds (mean, 0.65 second), and 0.78 to 2.5 seconds (mean, 1.25 seconds), respectively. In the hemodilution group, the mean hematocrit in microvessels was 0.28, which was 89% of the systemic hematocrit (0.32). Local cerebral blood flow was approximately 59% higher (P < .01) than that of the control animals. The rate of oxygen delivered to the brain was slightly increased (9%) after hemodilution. Blood volume in cerebral microvessels was similar to that of the control group. Mean transit time of blood was 0.62 second (68% of the control), transit time of red cells was 0.53 second (85% of the control), and transit time of plasma was 0.67 second (54% of the control).",
            "output": [
                "Does hemodilution accelerate the passage of plasma ( not red cells ) through cerebral microvessels in rats?"
            ]
        },
        {
            "id": "task847-b3ef37322d004926ba79b00ce02a92a3",
            "input": "Changes in vascular permeability are well-known and important consequences of cerebral ischemia. The development of edema and of petechial hemorrhage is connected to altered vascular integrity. A major part in microvascular integrity is played by the basal lamina.', 'The fates of the basal lamina components laminin, fibronectin, and type IV collagen during middle cerebral artery occlusion (2 hours, n = 3) and occlusion (3 hours) with reperfusion (1 hour, n = 3; 4 hours, n = 3; and 24 hours, n = 4) were evaluated in the nonhuman primate. Specific monoclonal antibodies against these components were used. The number and size distribution of the microvessels in each specimen were determined by video-imaging microscopy, and the relative fluorescence intensity of laminin was semiquantified by laser confocal microscopy. Basal lamina antigen presentations were compared by double-stain immunofluorescence histochemistry.', 'The number of microvascular structures defined by the presence of each basal lamina antigen decreased significantly up to 24 hours of reperfusion (P < .0001). The ratio of laminin-containing vessels between the ischemic and nonischemic territories decreased significantly from control (0.98 +/- 0.04) to 2 hours of ischemia (0.83 +/- 0.09) and 1 hour (0.79 +/- 0.08), 4 hours (0.77 +/- 0.06), and 24 hours of reperfusion (0.55 +/- 0.07). The ratio of fibronectin (cellular) and of collagen (IV)-containing vessels decreased from 0.98 +/- 0.04 to 0.75 +/- 0.1 and from 1.02 +/- 0.03 to 0.57 +/- 0.1, respectively. Mean laminin fluorescence intensity decreased from 76.1 +/- 6.0 U (controls) to 52.0 +/- 14.6 U (24 hours of reperfusion; P < .001).",
            "output": [
                "Do microvascular basal lamina antigens disappear during cerebral ischemia and reperfusion?"
            ]
        },
        {
            "id": "task847-abeaa20468084b4aba8239806babdd6c",
            "input": "N-Methyl-D-aspartate (NMDA) produces dilatation of cerebral arterioles that is dependent on production of nitric oxide (NO). In these experiments we examined the hypothesis that cerebral vasodilatation in response to NMDA is mediated by the neuronal isoform of NO synthase.', 'We measured diameters of cerebral arterioles (baseline diameter, 89 +/- 7 microns) using a closed cranial window in anesthetized rabbits that received either vehicle (10 mL/kg IP peanut oil) or 7-nitroindazole (7-NI; 50 mg/kg IP). 7-NI is reported to be a selective inhibitor of neuronal NO synthase.', 'Two hours after administration of 7-NI, activity of brain NO synthase (measured by conversion of L-arginine to L-citrulline) was reduced by 33% compared with vehicle (24 +/- 1 versus 16 +/- 3 pmol/min per milligram protein; n = 7; P < .05). Dilatation of cerebral arterioles in response to NMDA (100 and 300 mumol/L) was inhibited by 30% to 40% by 7-NI compared with responses in the presence of vehicle (23 +/- 6% versus 14 +/- 5% and 30 +/- 4% versus 21 +/- 5%, respectively; P < .05 for both concentrations; n = 10). In contrast, vasodilatation in response to acetylcholine (1 mumol/L) was similar in vehicle- and 7-NI-treated animals (17 +/- 5% versus 21 +/- 4%; P > .05).",
            "output": [
                "Does 7-Nitroindazole inhibit brain nitric oxide synthase and cerebral vasodilatation in response to N-methyl-D-aspartate?"
            ]
        },
        {
            "id": "task847-b4b37b673cda425a9385b90d2ee502d7",
            "input": "Guanylin activates an intestinal guanylate cyclase (GCC) and stimulates electrolyte movement across the gut epithelium. Cells expressing guanylin messenger RNA have been localized to the epithelial cell layer of the intestine; however, the identity of the guanylin-producing cells has not been determined. The aim of this study was to identify cells that express guanylin in the rat intestine.', 'Antibodies were raised against defined proguanylin epitopes, evaluated by Western blotting, and used for immunoperoxidase histochemistry.', 'Guanylin-like immunoreactivity was localized to a subset of goblet cells. In the small intestine, most, perhaps all, goblet cells in the villi were immunopositive, as were some goblet cells in upper crypts; however, goblet cells deep within crypts were unlabeled. In the colon, goblet cells clustered in the necks and around the openings of crypts were immunopositive, whereas (as in the small intestine) goblet cells in deeper crypt regions were unlabeled. In some animals, immunoreactive columnar epithelial cells were also observed in the colon (although such cells were not apparent in the small intestine). Relative labeling of columnar cells varied from animal to animal.",
            "output": [
                "Is guanylin , an endogenous ligand for C-type guanylate cyclase , produced by goblet cells in the rat intestine?"
            ]
        },
        {
            "id": "task847-bd47a952ded6498f89ffe75ed2223809",
            "input": "To assess the relationship between physicians' beliefs about the psychosocial aspects of patient care and their routine communication with patients.\", 'Fifty community primary care physicians participating in a continuing medical education program and 473 of their patients in Portland, Oregon.', 'Routine office visits were audiotaped and analyzed for communication behaviors and emotional tone using the Roter Interactional Analysis System (RIAS). Physician beliefs about psychosocial aspects of care were measured using a self-report questionnaire with a five-point Likert scale. Attitudes were correlated with communication behaviors using the Pearson correlation coefficient.', \"Physicians' attitudes toward psychosocial aspects of care were associated with both physician and patient dialogue in visits. The physicians who had positive attitudes used more statements of emotion (i.e., empathy, reassurance) (p < 0.05) and fewer closed-ended questions (p < 0.01) than did their colleagues who had less positive attitudes. The patients of the physicians who had positive attitudes more actively participated in care (i.e., expressing opinions, asking questions), and these physicians provided relatively more psychosocial and less biomedical information (p < 0.05).",
            "output": [
                "Do physicians ' psychosocial beliefs correlate with their patient communication skills?"
            ]
        },
        {
            "id": "task847-055233c3c68f44d195c1883686b6af88",
            "input": "To assess the effect of six different enteral diets on the gut barrier.', 'Laboratory study.', 'University hospital, Germany.', '70 Specific pathogen free female Crl:CDR BR rats.', 'For 7 days, 6 groups of rats were fed orally with standard chow (n = 15); total parenteral nutrition solution (oral TPN, n = 15); elemental diet (ED, n = 10); nutrient-defined diet (NDD, n = 10); or the NDD supplemented with uracil (NDD+uracil, n = 10), or fibre (NDD+fibre, n = 10).', 'Bacterial translocation to mesenteric lymph nodes, numbers of Gram negative enterobacteria and total aerobic bacteria in the caecum, and intestinal concentrations of secretory IgA.', 'The incidence of bacterial translocation was significantly increased in the groups given oral TPN, ED, NDD, and NDD+uracil compared with the group given chow. Only NDD+fibre resulted in a similar degree of translocation to that in the chow group. All groups in which there was increased translocation had a highly significant overgrowth of aerobic bacteria in the caecum, mainly by Gram negative enteric organisms. The secretory IgA concentration was reduced in the group that had been given oral TPN, and that in the ED and NDD+uracil groups was similar to that in the chow group. NDD and NDD+fibre were associated with higher intestinal concentrations of secretory IgA than chow.",
            "output": [
                "Is fibre an essential ingredient of enteral diets to limit bacterial translocation in rats?"
            ]
        },
        {
            "id": "task847-8fb5eca208e744988107b78303519c65",
            "input": "Epidermal growth factor (EGF) has been shown to induce intestinal proliferation and maturation; however, little information is available regarding substrates of the intestinal EGF receptor tyrosine kinase. The purpose of this study was to determine if src homologous collagen-like protein (Shc) was an in vivo substrate of the intestinal EGF receptor.', 'Ten-day-old rats were treated with EGF or were breast-fed. In some experiments, IEC-6 cells were treated with EGF. Intestinal tissue and cell fractions were studied by immunodetection to compare the tyrosine phosphorylation state and the subcellular localization of intestinal proteins.', 'The total tyrosine phosphorylation state of intestinal proteins was increased threefold by EGF. Tyrosine phosphorylation of the EGF receptor and Shc were rapidly increased by EGF. The association of Grb2 with Shc increased fourfold and fivefold. Plasma membrane translocation of Shc and associated phosphotyrosyl proteins was increased within 30 seconds of EGF treatment.",
            "output": [
                "Is shc a substrate of the rat intestinal epidermal growth factor receptor tyrosine kinase?"
            ]
        },
        {
            "id": "task847-0ac2888ccc55451bbfda3928331680a8",
            "input": "Azathioprine, an effective therapy for Crohn's disease, is limited by a prolonged time to response. The aim of this study was to determine the safety and utility of a loading dose of azathioprine to decrease the time to response in patients with Crohn's disease.\", \"Twelve patients were studied: 6 with 13 fistulae and 6 with inflammatory disease. All patients received an intravenous infusion of azathioprine (50 mg/h for 36 hours). Response was determined by physical and radiographic examination for fistulae and by the Crohn's Disease Activity Index for inflammatory disease. Erythrocyte concentrations of azathioprine metabolites were measured by chromatography.\", 'Seven of 13 fistulae closed by week 4, and three had a temporary decrease in drainage. One fistula improved at week 16. Two fistulae failed to improve. Four of 6 patients with inflammatory disease achieved remission, and 1 improved temporarily. Improvement was rapid (< or = 4 weeks). Peak concentrations of azathioprine metabolites occurred within 3 days. Clinical response did not correlate with azathioprine metabolite concentrations at the azathioprine dose studied. No adverse events occurred.",
            "output": [
                "Does an intravenous loading dose of azathioprine decrease the time to response in patients with Crohn 's disease?"
            ]
        },
        {
            "id": "task847-4ea0d43a62ee4c7e87ec3fbbbd98f41b",
            "input": "Microsatellite instability is a property of most tumors occurring in the context of hereditary nonpolyposis colon cancer. Instability also occurs in 10%-15% of apparently sporadic colorectal cancers, and it has been hypothesized that this instability may indicate a genetic predisposition to colonic cancer. This study evaluated whether there is a clinically useful association between colon cancer instability and a family history of cancer.', 'Colon cancer cases (n = 188) from a population-based study were evaluated for microsatellite instability with 10 polymerase chain reaction primer sets. Instability results were compared with family history and other clinical and biological characteristics.', 'Microsatellite instability was found in 16.5% of tumors. It was predominantly a feature of right-sided tumors (P = 0.003) and was associated with the youngest and oldest ages at diagnosis (P = 0.01). Instability was not associated with family history of cancer, sex of the individual, or the glutathione-S-transferase mu 1 null genotype.",
            "output": [
                "Is microsatellite instability in human colonic cancer a useful clinical indicator of familial colorectal cancer?"
            ]
        },
        {
            "id": "task847-a61ff595bf3642fcbc6081c8e227c54a",
            "input": "Thromboxane has been shown to contribute to coronary constriction in conduit coronary arteries during platelet aggregation at the site of a critical stenosis. Previous studies from our laboratory suggest that following a critical coronary stenosis, persistent vasomotor tone occurs. We tested the hypothesis that thromboxane is responsible for that increased tone.', 'To test this hypothesis, 14 mongrel dogs of either sex were anesthetized and subjected to a critical coronary stenosis where distal coronary perfusion pressure was reduced to 36 +/- 2 mm Hg. During the coronary stenosis, SQ 29,548 (thromboxane/endoperoxide receptor antagonist) was administered intravenously (0.2 mg/kg and 2.0 mg/kg). Coronary microvascular responses were observed by directly visualizing the epicardial microcirculation. Diameters were measured using intravital microscopy coupled to stroboscopic epi-illumination and jet ventilation to compensate for cardiac and respiratory-induced motion.', 'Coronary microvessels were divided into small (< 150 microns) and large (> 150 microns) arterioles. During SQ 29,548 administration, small coronary arterioles demonstrated no additional dilation during a critical coronary stenosis. In contrast, coronary microvessels > 150 microns demonstrated a dose-dependent vasodilation to SQ 29,548 (0.2 mg/kg: 6 +/- 2%; 2.0 mg/kg: 11 +/- 4%; P < 0.05 vs. no change). A time control study in six additional animals demonstrated no significant microvascular diameter changes following a critical stenosis over the time course of SQ 29,548 administration.",
            "output": [
                "Does thromboxane contribute to submaximal coronary dilation during myocardial ischemia?"
            ]
        },
        {
            "id": "task847-9aa78cf96e684c63a5ccceae7ff823b0",
            "input": "To determine the associations between serum cortisol and HDL cholesterol, other lipoprotein lipids and cardiovascular risk factors, carotid atherosclerosis, and clinical heart disease in older people.', 'A cross-sectional, observational, ancillary study of the Cardiovascular Health Study (CHS).', 'A total of 245 community-dwelling people, 65 to 89 years old, were recruited consecutively for a 2-month period from the CHS cohort in Forsyth County, North Carolina.', 'Cortisol was measured by radioimmunoassay in serum collected between 7:00 and 10:00 AM after an overnight fast. Cortisol levels were correlated with lipoprotein lipids, insulin, glucose, body mass index, waist-hip ratio, prevalent coronary heart disease, hypertension, diabetes, and carotid atherosclerosis by B-mode ultrasound.', 'Serum cortisol was correlated negatively (r = -.24) with body mass index and waist-hip ratio (r = -.16) but was not related significantly to fasting insulin or glucose. Cortisol was not associated significantly with triglyceride and low density lipoprotein cholesterol but showed a positive correlation (r = .21) with high density lipoprotein cholesterol. The relationship between cortisol and high density lipoprotein cholesterol persisted after adjustment for gender, body mass index, waist-hip ratio, cigarette and alcohol use, triglyceride level, and diabetes. There was a trend toward a negative correlation between cortisol and measures of carotid atherosclerosis, but no significant relationship was indicated between cortisol and prevalent coronary heart disease, hypertension, or diabetes.",
            "output": [
                "Is high density lipoprotein cholesterol associated with serum cortisol in older people?"
            ]
        },
        {
            "id": "task847-5e5cb7dd62964b85933e79f3663ccaee",
            "input": "The safety of silicone breast implants recently has been questioned. Increasing numbers of women have reported a variety of health problems that they attribute to their implants. The purpose of this descriptive study was to explicate the phenomenon of silicone-related illness as reported by women who have had breast implants.', 'A qualitative design was grounded in the theoretical framework proposed by McBride and McBride (1981), the core of which is the first-person, lived experiences of women as interpreted and explained by the women themselves.', 'Participants were recruited through Command Trust Network, an international support group for women with breast implant problems. The sample consisted of 55 women from 19 states and Canada who experienced health problems they attributed to their implants. Eighteen percent labeled themselves as disabled.', 'Themes emerging from responses to 10 questions are discussed in terms of circumstances leading to initial implantation, understanding risks and benefits, health problems and symptoms, physician response, choices made about implant removal, and psychosocial and emotional consequences.",
            "output": [
                "Do women 's reports of breast implant problems and silicone-related illness?"
            ]
        },
        {
            "id": "task847-198a0826d3f4403498ec7b4c6fefdfab",
            "input": "The purpose of this study was to characterize the hemodynamic changes in the contralateral testis during acute spermatic cord torsion in anesthetized rats.', 'We used videomicroscopy to examine the microcirculation of the contralateral testis following acute torsion. Specifically, we examined the effect on vasomotion, a rhythmic dilation and constriction of the arterioles that is involved in fluid and nutrient exchange and modulation of local vascular resistance. In a separate set of experiments, blood flow in the contralateral internal spermatic artery was measured with an ultrasonic flow probe during acute torsion.', \"Following 720 degrees torsion, the amplitude of vasomotion in the contralateral testis increased 121% (29.0 +/- 3.9% versus 13.0 +/- 1.7%) compared with controls. Blood flow in the contralateral internal spermatic artery decreased 43% after 2 hours' torsion.",
            "output": [
                "Does acute spermatic cord torsion alter the microcirculation of the contralateral testis?"
            ]
        },
        {
            "id": "task847-5c973d549222405382e9c21bfb78caf1",
            "input": "Oxidative stress in reflux esophagitis was investigated before and after antireflux surgery.', \"Oxidative stress was studied in the distal and proximal esophagus of control patients (without esophagitis, but with other gastrointestinal disorders), of patients with various grades of esophagitis (including Barrett's esophagus), and in patients who had a Nissen fundoplication. Oxidative stress was assessed by chemiluminescence, lipid peroxidation (LP), and by measuring superoxide dismutase (SOD).\", \"Chemiluminescence and LP increased with the degree of esophagitis and was highest in patients with Barrett's esophagus; SOD decreased with damage, except in cases of Barrett's esophagus associated with mild esophagitis. Chemiluminescence and LP in reflux patients were higher in the distal than in the proximal esophagus, and SOD was lower, whereas no such difference was found in controls. Findings after Nissen fundoplication were similar to those of controls.",
            "output": [
                "Is reflux esophagitis in humans mediated by oxygen-derived free radicals?"
            ]
        },
        {
            "id": "task847-0b0cc559bffd40f6a2e0033bfda0e98f",
            "input": "Epinephrine commonly is added to epidural opioids and local anesthetics, however, little is known about the fate of epidurally administered epinephrine. Studies have identified the epinephrine metabolizing enzyme, catechol-O-methyl transferase (COMT), in the cranial meninges of several species. The purpose of this study was to determine whether the spinal meninges also contain COMT and are capable of metabolizing epinephrine. If so, then the spinal meninges may have an important impact in limiting the bioavailability of epinephrine in both the spinal cord and epidural space.', 'Spinal meningeal specimens measuring 4 cm2 were obtained from monkeys (M. nemestrina) and farm-bred pigs and were incubated in bicarbonate-buffered mock cerebrospinal fluid. Epinephrine (200 micrograms base) was added at t = 0, and 200 min later, the mock cerebrospinal fluid was collected for metanephrine analysis. In separate experiments, pig meningeal specimens were separated into dura mater, pia-arachnoid mater, and pia mater, and the experiments were repeated to determine which meninx had the greatest COMT activity.', 'Metanephrine was produced by monkey meninges at the rate of 0.47 ng.min-1.cm-2 and by pig meninges at the rate of 0.23 ng.min-1.cm-2 (P > 0.05). The pia-arachnoid meninx produced metanephrine at a greater rate (4.48 +/- 0.46 ng.min-1.mg-1 tissue) than did the pia mater (1.3 +/- 0.15 ng.min-1.mg-1 tissue) or dura mater alone (1.82 +/- 0.23 ng.min-1.mg-1 tissue).",
            "output": [
                "Is epinephrine metabolized by the spinal meninges of monkeys and pigs?"
            ]
        },
        {
            "id": "task847-16d234ee57394b8a9c6824b0ec7e9a1c",
            "input": "The need for liver biopsy is increasing with the increasing availability of treatments for liver disease, in particular interferon. For this reason the procedure must be efficient and economical, as well as safe.', \"Firstly to assess the safety of outpatient liver biopsy when performed with ultrasound guidance and the 'Biopty' gun. Secondly, to compare the cost of an outpatient and inpatient procedure.\", \"Two hundred and fifty consecutive liver biopsies performed over a two year period at St Vincent's Hospital, Melbourne were reviewed retrospectively. Indications, histological findings and complications were recorded.\", 'Seventy per cent of the biopsies were performed as an outpatient procedure. There were no major complications. Four patients experienced prolonged pain post biopsy. The average cost for an outpatient biopsy was $351, the cost of an inpatient (overnight stay) was $690.",
            "output": [
                "Is outpatient liver biopsy using ultrasound guidance and the Biopty gun safe and cost effective?"
            ]
        },
        {
            "id": "task847-718a8c9819e9414c901b9fe739bf62b8",
            "input": "To investigate the existence of a water channel in the frog corneal epithelium by studying the osmotic water permeability (Pf) of Xenopus oocytes expressing the mRNA message from frog corneal epithelium.', 'Total RNA was obtained from corneal epithelium by a single-step phase separation method, and poly A+ RNA was isolated using oligo-dT columns. This mRNA was injected into the oocytes. After a 48-hour incubation, oocyte volume changes elicited by a hypoosmotic solution were measured with a computerized video system.', 'Oocytes injected with 50 nl mRNA (1 microgram/microliter) showed a significant increase in Pf compared to water-injected controls (8.4 +/- 1.5 to 17.5 +/- 1.9 cm.sec-1 x 10(-4), P < 0.005). mRNA-injected oocytes exposed to a higher external [Cl-] showed a heightened permeability. Furthermore, Pf of oocytes exposed to a solution containing the recognized water-channel blocker HgCl2 was significantly lower than the Pf of mRNA-injected oocytes not exposed to HgCl2.",
            "output": [
                "Does mRNA from frog corneal epithelium increase water permeability in Xenopus oocytes?"
            ]
        },
        {
            "id": "task847-3786a3fe78bb49d595cfbfced22d7280",
            "input": "Dimethyl sulfoxide (DMSO), an agent that provides symptomatic relief in patients with interstitial cystitis (IC) works via an unknown mechanism. We investigated whether DMSO acts as a chemical stimulant of mast cell degranulation.', 'A radioimmunoassay (RIA) specific for histamine was used to test this hypothesis. Twelve women with strictly diagnosed IC were treated with intravesical instillations of DMSO. Treatments were repeated at varying intervals, and each patient received three to six treatments. Urine histamine levels were measured before and after each intravesical instillation of DMSO. Dilutional effects of DMSO were corrected for by conversion of urine histamine concentration to urine histamine:creatinine ratio.', 'The RIA was unaffected by the addition of DMSO to urine. No consistent change in the urine histamine:creatinine ratio following DMSO instillation was found. Trend analysis revealed no trend in the histamine:creatinine ratio with time.",
            "output": [
                "Does dimethyl sulfoxide trigger urine histamine release in interstitial cystitis?"
            ]
        },
        {
            "id": "task847-c29314c1b59d42aab42a8d9c73b3e056",
            "input": "Adenylyl cyclase is a transmembrane signaling system involved in the inhibition of cellular responses. Recently, we showed that the activity of adenylyl cyclase may be potentiated by stimuli that induce an increase of cellular responses but that do not activate adenylyl cyclase. This is probably an important physiologic feedback mechanism that prevents cells from becoming \"overstimulated.\"', 'Because increased cellular activities are frequently observed in persons with asthma, we hypothesized that a defect in potentiation of adenylyl cyclase might be involved.', 'Potentiation of isoprenaline-induced adenosine cyclic monophosphate (cAMP) production with the mitogen phytohemagglutin (PHA; 45 micrograms/ml) or the calcium ionophore A23187 (1 mumol/L) was studied in peripheral blood mononuclear cells taken from patients with asthma (n = 8) and healthy control subjects (n = 11).', 'Isoprenaline-induced cAMP production was potentiated significantly in the healthy control subjects (PHA, 110% +/- 15%; A23187, 92% +/- 25%). In contrast, potentiation was not seen with PHA or A23187 in the total group of patients with asthma. However, some patients showed weak potentiation, whereas in others PHA decreased isoprenaline-induced cAMP production. Moreover, the effect of PHA on isoprenaline-induced cAMP production correlated significantly with the degree of bronchial hyperreactivity in patients with asthma (r = 0.96; p = 0.0001).",
            "output": [
                "Does defect in potentiation of adenylyl cyclase correlate with bronchial hyperreactivity?"
            ]
        },
        {
            "id": "task847-d2cfc4596e154103a367e98ed9db4b65",
            "input": "The detection of asymptomatic embolic signals by Doppler ultrasound may offer a powerful investigational tool in the management of cerebrovascular disease. However, early studies, particularly in patients with carotid artery disease, have reported very different frequencies of embolic signals. While this may reflect differences in patient groups and the criteria used for embolic signal identification, the degree of time-window overlap may be important. If this is insufficient, some embolic signals may fall between two time windows and not appear on the spectral display. Furthermore, the use of nonrectangular time windows, such as the Hanning window, may result in variation of the intensity of an embolic signal depending on where it is detected within the time window.', 'To test the importance of this potential problem, the same 25 embolic signals recorded as the audio signal on digital audiotape were each played repeatedly through a transcranial Doppler ultrasound (TCD) system using fast Fourier transform analysis. An older system with no time-window overlap was used, and a more modern system was also used in which three different degrees of overlap were used: -9%, 27%, and 57%. The number of signals audible but not appearing on the spectral display was recorded. The variability in the relative intensity increase for the same embolic signal played repeatedly was estimated by calculating the coefficient of variation of the relative intensity increase.', 'With the older system, 39/500 (7.8%) of embolic signals were missed. With the newer system, the number of embolic signals missed was fewer and decreased with increasing degrees of overlap (10/500 for -9% overlap, 1/500 for 27% overlap, and 0/500 for 57% overlap). For those setups in which embolic signals were missed, there was a highly significant relationship between duration of embolic signal and number of signals missed. In parallel with these results, the coefficient of variation of the relative intensity increase became progressively less with increasing degrees of time-window overlap. For all processing setups, the coefficient of variation was greater for the less intense and shorter duration signals, but this dependence, as estimated by the slope of the regression line, became less strong with higher degrees of overlap.",
            "output": [
                "Do importance of time-window overlap in the detection and analysis of embolic signals?"
            ]
        },
        {
            "id": "task847-540025136aae4ab78aab06b027a78658",
            "input": "Our purpose was to determine whether nuchal thickness measurement can identify the euploid fetuses in midtrimester pregnancies at increased risk for Down syndrome on the basis of maternal age and serum screening.', \"Nuchal thickness was obtained prospectively in 651 consecutive fetuses at 14 to 21 weeks' gestation and at > or = 1:270 risk for Down syndrome on the basis of unconjugated estriol, alpha-fetoprotein, and human chorionic gonadotropin levels. The risk of Down syndrome with a normal nuchal thickness was determined. A receiver-operator characteristic curve was used to determine a serum-based risk threshold below which the risk for Down syndrome was low. The prevalence of Down syndrome in fetuses with both a normal nuchal thickness and a below-serum-risk threshold was compared with prevalence in either those above threshold risk or with an abnormal nuchal thickness.\", 'There were eight cases of trisomy 21 and one case each of 46,XX/47,XXX, 46,XY/47,XY, +7, and 46,XX, 11q-. The sensitivity of an abnormal nuchal thickness (> or = 6 mm) for detecting Down syndrome was four in eight (50%) (95%) confidence interval 15.3% to 84.6%). The risk of Down syndrome was significantly increased with an abnormal compared with a normal nuchal thickness, four in 13 (30.8%) versus four in 638 (0.6%), p < 0.0001. A risk threshold was defined at > or = 1:100 on the basis of the receiver-operator characteristic plot. Of 390 cases with a normal nuchal thickness and a serum risk estimate < 1:100, there were no cases of Down syndrome (0/390 vs 8/253, p = 0.002).",
            "output": [
                "Does normal nuchal thickness in the midtrimester indicate reduced risk of Down syndrome in pregnancies with abnormal triple-screen results?"
            ]
        },
        {
            "id": "task847-3fa1712f6cc643f4bcde2d9488e378c7",
            "input": "The cost effectiveness of preoperative localization in cases of primary hyperpara-thyroidism has not been established. We analyzed the potential savings in operative time after localization with technetium 99m (99mTc) sestamibi scan.', 'Thirty-three patients had localization of a solitary adenoma with 99mTc-sestamibi. Measurement was made of the time required for adenomectomy, unilateral neck exploration (UNE), unilateral neck exploration and confirmation of one contralateral parathyroid gland (UNEC), or bilateral neck exploration (BNE).', 'The total operative time in minutes was 76.4 +/- 18.8 for adenomectomy; 87.5 +/- 20.4 for UNE; 105.6 +/- 25.0 for UNEC; and 117.9 +/- 26.7 for BNE. The time difference was significant between adenomectomy versus UNE, UNEC, and BNE. There were also significant time differences between UNE versus UNEC and BNE.",
            "output": [
                "Do analysis of savings in operative time for primary hyperparathyroidism using localization with technetium 99m sestamibi scan?"
            ]
        },
        {
            "id": "task847-0f005bde4e6a453f987cba64584db180",
            "input": "Pretreatment of magnesium sulfate (MgSO4) attenuates pressor response associated with endotracheal intubation. Vasodilating effect of MgSO4 may increase cerebral blood flow, which upsets the known benefit to cardiovascular hemodynamic. In the present study, we evaluated the effect of MgSO4 on the changes of cerebral blood flow in response to endotracheal intubation.', 'Twenty four ASA class I or II patients who randomly received either normal saline 5 ml or MgSO4 (60 mg/kg, i.v.) 3 min before induction of anesthesia were included in the study. Mean blood flow velocity (VMCA) of the middle cerebral artery was obtained using a transcranial Doppler sonography (TCD) before and after endotracheal intubation. Anesthesia was induced with fentanyl (4 micrograms/kg) and thiopental (5 mg/kg) and endotracheal intubation was facilitated with succinylcholine (1.5 mg/kg).', 'Before endotracheal intubation, MgSO4 caused a transient decrease in VMCA (98 +/- 6% vs. 76 +/- 3% of baseline) and increase in heart rate (132% vs. 114% of baseline) compared to saline group. However, VMCA and heart rate did not show significant difference in both groups after tracheal intubation. Also, systolic and diastolic blood pressure did not differ during the study.",
            "output": [
                "Does magnesium sulfate have negligible effect on middle cerebral artery blood flow velocity in response to endotracheal intubation?"
            ]
        },
        {
            "id": "task847-fcd6b7936bfd410fabda2db3461c5052",
            "input": "Accurate sampling of gallbladder bile for biliary analysis is essential for determining any potential difference between combined bile acid therapy and monotherapy in gallstone patients.', 'In 104 gallstone patients undergoing extracorporeal shock wave lithotripsy with following bile acid therapy [either chenodeoxycholic acid (500 mg/day) and ursodeoxycholic acid (500 mg/day), group I (n = 53), or ursodeoxycholic acid alone (1000 mg/day), group II (n = 51)], bile samples, obtained by direct fine needle puncture of the gallbladder, were investigated for biliary lipids, total biliary protein concentration, and nucleation time before and after 12 months of bile acid therapy.', 'Initially, a negative correlation was found between nucleation time and number of gallstones and between total biliary protein concentration and nucleation time (r = -0.52 and r = -0.49 in group I vs r = -0.56 and r = -0.51 in group II, p < 0.01 in each group). The correlation between total biliary protein concentration and nucleation time was also found after 12 months of bile acid treatment (r = -0.54 in group I vs r = -0.47 in group II, p < 0.01 in each group). In group I, the decrease in cholesterol saturation index, biliary cholesterol, cholic acid, deoxycholic acid, and total protein concentration was more pronounced than in group II (p < 0.01). The same effect was found concerning the prolongation of nucleation time (p < 0.01). Furthermore, dissolution rates were higher in group I compared with group II (80.4 vs 69.0%, p < 0.01).",
            "output": [
                "Is combined bile acid therapy more effective on biliary lipids and dissolution rates than monotherapy after gallstone lithotripsy?"
            ]
        },
        {
            "id": "task847-7e04a0b4cb7f406d9f2680fd80a4058f",
            "input": "We determined the neuropathologic damage in a canine model of global incomplete ischemia commonly used in a variety of physiological experiments.', 'We induced 20 minutes of incomplete ischemia in dogs (n = 9) by increasing intracranial pressure via intraventricular infusion of artificial cerebrospinal fluid to maintain a cerebral perfusion pressure of 10 mm Hg while keeping body temperature at 38 degrees C during and immediately after ischemia. After a 7-day recovery period, animals were perfusion-fixed for neuropathology. In hematoxylin and eosin preparations, ischemic neuronal injury was assessed, neurons were counted, and percentage of cell damage was determined.', 'No focal neurological deficits or overt seizures were observed during the 7-day recovery period. In superior temporal gyrus, 49 +/- 11% and 70 +/- 10% damage (mean +/- SEM) was observed in layer III pyramidal cells in the crown and sulcus, respectively. All neocortical regions examined showed neuronal damage in layers III and/or V. In hippocampus, 59 +/- 11% damage of pyramidal neurons occurred in CA1, with dorsal (septal) hippocampus showing more injury than ventral (temporal) portions. The caudate nucleus (head) exhibited 27 +/- 7% neuronal injury. In cerebellar cortex (anterior lobule), 70 +/- 7% damage of Purkinje cells occurred, but different folia of cerebellum showed varying degrees of injury. Brain stem and thalamus were minimally affected despite reduced blood flow. Inflammatory changes (leukocytic infiltration and neuronal incrustations) were observed, but only when neuronal degeneration was severe. Pancellular necrosis and infarction did not occur.",
            "output": [
                "Does global incomplete cerebral ischemia produce predominantly cortical neuronal injury?"
            ]
        },
        {
            "id": "task847-f49879ef9c0843e598b533266fa2eef4",
            "input": "Basic Fibroblastic Growth Factor (bFGF) is a powerful mitogen for smooth muscle cells and has been implicated in the genesis of Myointimal hyperplasia. The aim of this study was to determine the release of bFGF by veins in different haemodynamic conditions.', 'Laboratory animal study.', 'In 39 Lewis rats, a 1 cm long segment of inferior vena cava was inserted at the level of the abdominal aorta. The segments of inferior vena cava were obtained from syngenic Lewis rats. Arterial Vein Grafts (AVG) were harvested after 4 weeks (AVG 4) and 12 weeks (AVG 12). In 16 animals the arterial vein grafts were explanted 4 weeks after the initial operation and reimplanted (Reimplanted Vein Grafts: RVG) in syngenic Lewis rats as venous-venous bypass grafts at the level of the left iliac vein and harvested after 2 weeks (RVG 2) and 8 weeks (AVG 8).', 'The tissue was studied in organ culture in a serum-free system for (1) release of bFGF (immunoassay) and (2) mitogenic activity of the conditioned media. Scanning electron and light microscopy studies were also performed.', 'bFGF release by veins increased significantly (p < 0.01) when veins were inserted in the arterial circulation, and decreased significantly (p < 0.01) when grafts were reimplanted in the venous system. bFGF release (ng/cm2): [Formula: see text]",
            "output": [
                "Is bFGF release dependent on flow conditions in experimental vein grafts?"
            ]
        },
        {
            "id": "task847-b59c3ec5c9ab482597153163bf79801a",
            "input": "Our purpose was to evaluate fetal fibronectin, interleukin-6, and C-reactive protein from patients with preterm labor to establish prognostic subcategories.', 'Thirty-seven patients with preterm labor had cervical fetal fibronectin and plasma C-reactive protein sampled. Eighteen of these patients had amniotic fluid interleukin-6 levels measured. Outcome variables were (1) delivery before 34 weeks and (2) delivery within 48 hours.', \"Detectable cervical fetal fibronectin identified 89% of patients who were delivered before 34 weeks' gestation. Interleukin-6 > 1500 pg/ml identified 88% of patients who were delivered within 48 hours. C-reactive protein > 1.5 mg/dl correlated with elevated interleukin-6 levels (p < 0.001).",
            "output": [
                "Are fetal fibronectin , interleukin-6 , and C-reactive protein useful in establishing prognostic subcategories of idiopathic preterm labor?"
            ]
        },
        {
            "id": "task847-a9790f6ed14e4febafa1745a09731489",
            "input": "To investigate the role of T helper-1 cell (Th1) activation in the induction of proinflammatory cytokine production and cartilage damage by rheumatoid arthritis (RA) synovial fluid mononuclear cells (SFMNC) and the subsequent possible beneficial role of the T helper-2 cell (Th2) cytokine interleukin-4 (IL-4) in the inhibition of this process.', 'SFMNC were stimulated with bacterial antigen (hsp60) to activate Th1 cells. Th1 and Th2 specific cytokine profiles (interferon gamma (IFN gamma) and IL-4) and proinflammatory cytokines interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF alpha) in the conditioned media were analysed. In addition, the conditioned media were tested for their ability to induce cartilage damage. The same parameters were measured in the presence of IL-4.', 'Stimulation of SFMNC with bacterial antigen resulted in an increase in IFN gamma, IL-1, and TNF alpha production which was accompanied by the induction of cartilage damage. Th1 activation could be inhibited by IL-4 as shown by a reduction of IFN gamma. This was accompanied by a decrease in IL-1 and TNF alpha production and inhibition of cartilage damage.",
            "output": [
                "Is proinflammatory cytokine production and cartilage damage due to rheumatoid synovial T helper-1 activation inhibited by interleukin-4?"
            ]
        },
        {
            "id": "task847-9967638770d84f6989100e8ed07d1d31",
            "input": "To determine daily production of nitric oxide (NO) measured as urinary nitrate excretion, and the effect of prednisolone in patients with rheumatoid arthritis (RA).', 'Twenty four hour urinary nitrate was measured by gas chromatography in 10 patients with RA, before and two to four weeks after commencement of prednisolone 0.5 mg/kg body weight, and in 18 healthy controls.', 'Before the start of prednisolone treatment the urinary nitrate excretion in patients with RA was 2.7-fold greater (p < 0.001) than that in healthy volunteers. After prednisolone it decreased significantly, by 28%, at which time inflammatory activity (as indicated by C reactive protein, erythrocyte sedimentation rate, joint count, and early morning stiffness) was also reduced considerably. Despite this decrease, the urinary nitrate excretion in patients with RA remained twice that in the control group (p < 0.05).",
            "output": [
                "Is urinary nitrate excretion increased in patients with rheumatoid arthritis and reduced by prednisolone?"
            ]
        },
        {
            "id": "task847-cb5143a1ef714322a9cdfb774cba3a26",
            "input": "To determine the incidence of microvascular invasion in prostatic carcinoma and its correlation with other prognostic factors.', 'Evaluation of the frequency and extent of microvascular invasion by routine light microscopy in 210 whole-mounted radical prostatectomies with cancer.', 'Microvascular invasion was identified in 111 (53%) of 210 specimens. Focal microvascular invasion (involvement of fewer than three high-power fields) was present in 42 cases (20%); extensive microvascular invasion (involvement of three or more high-power fields) was present in 69 cases (33%). Capsular perforation was present in 43% and 62% of cases with focal and extensive microvascular invasion, respectively. Seminal vesical involvement was observed in 23% and 47% of cases with focal and extensive microvascular invasion, respectively. Lymph node metastases were only observed in cases with microvascular invasion and were present in 7% and 23% of cases with focal and extensive invasion, respectively. There was also a strong positive correlation of microvascular invasion with surgical margin status, Gleason score, and cancer volume. Tumors ranged in volume from 0.14 cc to 47.25 cc (mean, 9.09 cc), and the volume in cases without microvascular invasion was lower than in those with invasion (mean, 5.4 cc and 12.7 cc, respectively); also, the volume in cases with focal invasion was lower than in those with extensive invasion (mean, 9.4 cc and 16.1 cc, respectively).",
            "output": [
                "Does microvascular invasion in prostate cancer correlate with pathologic stage?"
            ]
        },
        {
            "id": "task847-58e718ab8ec04b84a7355188169b739d",
            "input": "There is increasing evidence that immune processes are important in the development of atherosclerosis. We investigated whether low density lipoprotein (LDL) adsorption therapy affected serum cytokine levels and the expression of adhesion molecules on peripheral blood mononuclear cells (lymphocytes and monocytes) in patients with arteriosclerotic obliterance (ASO).', \"LDL adsorption therapy was repeated ten times over a period of three months in ten ASO patients. The total serum cholesterol and LDL cholesterol levels were significantly reduced at the end of therapy. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured serum levels of inflammatory cytokines (interleukin-1 beta (IL-1 beta), IL-6 and tissue necrosis factor alpha (TNF-alpha)) and expression of adhesion molecules (lymphocyte function-associated antigen 1 alpha (LFA-1 alpha), LFA-1 beta, CD2, very late antigen (VLA)-4, VLA-5 and CD44) on mononuclear cells in the same patients and a group of healthy subjects. Serum levels of all inflammatory cytokines were markedly higher in ASO patients compared with healthy subjects, but there was no significant difference in the level before and after LDL adsorption. VLA-4 expression on CD3+ cells, but not of other adhesion molecules, was markedly higher in ASO patients compared with healthy subjects. LDL adsorption caused a significant reduction in CD2, VLA4 and VLA-5 expression on CD3+ cells. Furthermore, VLA-4 and VLA-5 expression on monocytes diminished significantly after LDL adsorption.",
            "output": [
                "Does removal of LDL from plasma by adsorption reduce adhesion molecules on mononuclear cells in patients with arteriosclerosis obliterans?"
            ]
        },
        {
            "id": "task847-c5501ea39def4b9786d981111fdc84f9",
            "input": "Intestinal reflexes induced by distention in dogs are facilitated by either simultaneous or previous distentions. The aim of this study was to determine whether these phenomena also modulate the responses to intestinal distention, particularly perception, in humans.', 'Perception and intestinal relaxation were measured in 11 healthy subjects in response to increasing jejunal balloon distentions tested (by stimulus-response trials) alone, as control, and with conditioning distentions applied either simultaneously, immediately (10 seconds) before at the same site, or immediately before and 5 cm distant. In 8 additional subjects, the effect of prolonged (90-minute) conditioning distention was tested.', 'Conditioning had more pronounced effects on perception than on intestinal reflexes. Perception of intestinal distention increased (by 84 +/- 47%; P < 0.05) when a simultaneous distention was applied nearby. By contrast, perception decreased (by 38 +/- 12%; P < 0.05) when a previous distention was applied at the same but not at an adjacent site. Prolonged intestinal distention elicited remarkably stable perception during a 90-minute period. The effects of conditioning were unrelated to intestinal compliance because it remained unchanged.",
            "output": [
                "Are perception and reflex responses to intestinal distention in humans modified by simultaneous or previous stimulation?"
            ]
        },
        {
            "id": "task847-912acf0415a24571ac45f51f185f2133",
            "input": "To compare rates of undertriage and overtriage of six ambulance dispatch protocols for the presenting complaint of nontraumatic abdominal pain, and to identify the optimal protocol.', 'Retrospective prehospital and emergency department chart review to classify patients\\' conditions as \"emergency\" or \"nonemergency.\" Utility analysis was used to identify the preferred protocol and monetary cost-effectiveness analysis to identify the least expensive protocol.', 'County emergency medical services (EMS) system with five receiving hospitals serving a mainly urban population of approximately 350,000.', 'Records of 902 patients who called 911 for nontraumatic abdominal pain were reviewed; patients not transported were excluded. Twenty-seven county EMS medical directors completed questionnaires.', 'Six ambulance dispatch protocols for nontraumatic abdominal pain were developed: indiscriminate-dispatch, four selective protocols, and no-dispatch. A dichotomous classification system was derived prospectively from the prehospital and medical records of patients who had activated the EMS system before the study period to define \"emergency\" and \"nonemergency\" conditions associated with nontraumatic abdominal pain. Emergency criteria identified patients with conditions requiring medical treatment within 1 hour. Reviewers determined, for each patient, whether an ambulance would have been dispatched by each of the protocols. Undertriage and overtriage rates were calculated for each protocol. County EMS medical directors assigned utility values to four potential outcomes of ambulance dispatch by the direct scaling method. The outcomes comprised correct and incorrect decisions to dispatch ambulances to patients with and without emergencies. The protocols were compared by decision analysis. A cost analysis was also performed, using an estimated marginal cost per transport of $302. Sensitivity analysis demonstrated the effect of varying the cost of an undertriage error and the cost per response. Of the 788 patients included in the study, 7.8% had conditions defined as emergencies. The four selective ambulance dispatch protocols had overtriage rates ranging from 10% to 51% and undertriage rates of 4% to 7%. None of the protocols was proven superior on the basis of the medical directors\\' assignment of utility values. The marginal cost of dispatching advanced life support ambulances to all patients with this complaint was $3,838 per emergency.",
            "output": [
                "Do comparison of ambulance dispatch protocols for nontraumatic abdominal pain?"
            ]
        },
        {
            "id": "task847-69cf6b65a9b1400ebd8221dff92dbdb2",
            "input": "The objective of this study was to describe a pattern of recovery and histological nerve cell loss in Sprague-Dawley rats exposed to severe brain ischemia and to compare it to that of Wistar rats.', 'Ether- and ketamine-anesthetized Sprague-Dawley rats were exposed to 3, 5, 6 and 10 min of normothermic severe brain ischemia (4 groups) induced by hypotension and neck compression. In group No. 5, the brain temperature was rapidly lowered, after 10 min of ischemia, to 30 degrees C during 45-50 min of recirculation. Wistar rats (group No. 6) served as controls (10-min normothermic ischemia).', 'In Sprague-Dawley (S-D) rats, post-ischemic audiogenic seizures (PAS) increased with the duration of ischemia and reached 86% (6/7 rats), after 10 min of ischemia. Mortality rate was high (50% = 7/14 rats). No seizure activity was observed after 10 min of ischemia in 6 Wistar (W) rats, and all survived. In the S-D rats, 10 min of ischemia produced histopathological damage in all brain regions examined, except in the thalamus. Damage was less severe in the W rats. Post-ischemic hypothermia ameliorated hippocampal and cortical nerve cell damage, but had no effect on the incidence of PAS activity and mortality. In W rats, hippocampal nerve cell loss was much less severe than in the S-D rats and cortical damage was not observed.",
            "output": [
                "Does post-ischemic hypothermia ameliorate ischemic brain damage but not post-ischemic audiogenic seizures in rats?"
            ]
        },
        {
            "id": "task847-2042fc2f566d42aab9e30e4db71c49fa",
            "input": "To determine the influence of ketamine on endotoxin-induced leukocyte adherence and venular microhemodynamics.', 'Randomized, controlled trial.', 'Experimental laboratory.', 'Thirty male Wistar rats.', 'The rats were pretreated with ketamine (10 mg/kg iv) or 0.9% saline, and both groups were given endotoxin (Escherichia coli lipopolysaccharide; 5 mg/kg iv). The control group received two doses of 0.9% saline.', 'The rates of leukocyte adherence and changes in microhemodynamics were monitored in rat mesenteric venules, using in vivo video microscopy. The number of adherent leukocytes was determined on-line in 10-min intervals from 60 mins before until 2 hrs after endotoxin administration. Venular diameters, red blood cell velocity, volumetric blood flow, and the venular wall shear rate were monitored before and at 10, 30, and 60 mins after endotoxin exposure. A 6.3-fold increase in the number of adherent leukocytes was observed 10 mins after administration of endotoxin when compared with control animals (5.87 +/- 0.69 vs. 0.93 +/- 0.21 adherent cells/100 microns; p < .001). This increase remained unchanged for 120 mins. In ketamine-pretreated rats, a 2.6-fold increase in leukocyte adherence occurred during the first 20 mins after endotoxin exposure (2.40 +/- 0.46 vs. 0.93 +/- 0.21 adherent cells/100 microns; p < .01). However, no difference in the number of adherent leukocytes between ketamine-pretreated and control animals was found after this 20-min period. In animals of the control group, no increase in leukocyte adherence occurred during the entire observation time. Diameters of mesenteric venules did not change after endotoxin exposure in any of the groups. Red blood cell velocity and venular blood flow in the endotoxin-treated groups decreased 10 mins after the injection of endotoxin when compared with controls, but these values did not show any difference when they were compared between ketamine and saline-pretreated animals. Similarly, venular wall shear rate in the endotoxin-treated groups decreased 10 and 30 mins after injection of endotoxin. However, no significant difference occurred between ketamine and saline-pretreated animals.",
            "output": [
                "Does ketamine attenuate endotoxin-induced leukocyte adherence in rat mesenteric venules?"
            ]
        },
        {
            "id": "task847-8d7c8ae5eb81498c90998ae60382bb0c",
            "input": "To determine the association of ethanol intoxication with hypoglycemia in ED patients.', 'Retrospective, laboratory log review of 953 consecutive patients who were evaluated for ethanol intoxication in an urban university hospital ED over a three-month period. Simultaneous serum glucose determination was carried out for each patient and associations between ethanol level and glucose were sought.', 'Glucose concentrations were unavailable for 16 patients (1.7%). Of the remaining patients, 584 patients had detectable ethanol concentrations (ethanol-positive), and 353 had no detectable ethanol (ethanol-negative). Ethanol concentrations (mean +/- SD) in the ethanol-positive group were 50.11 +/- 24.08 mmol/L (231 +/- 111 mg/dL), and glucose concentrations were 5.83 +/- 1.94 mmol/L (105 +/- 35 mg/dL). Hypoglycemia [glucose < 3.72 mmol/L (67 mg/dL)] was observed for five (0.9%) ethanol-positive patients. It was classified as mild-moderate [2.78-3.66 mmol/L (50-66 mg/dL)] for four patients (0.7%) and severe [< 2.78 mmol/L (50 mg/dL)] for one (0.2%). Ethanol concentrations ranged from 25.60 to 68.33 mmol/L (118 to 315 mg/dL). There was no correlation between ethanol and glucose concentrations in any subset of the ethanol-positive patients population. In the ethanol-positive group, patients who had several ethanol-positive visits (56 patients, mean 3.6 visits/patient) accounted for four of the five episodes of hypoglycemia, including the one episode of severe hypoglycemia. The frequency of hypoglycemia in repeat visitors (2.0%) was higher than that in the group of patients without repeat visits (0.2%). In the ethanol-negative group, there were four (1.1%) episodes of mild-moderate hypoglycemia and no severely hypoglycemic patients. Hypoglycemia was not more likely to occur among ethanol-positive patients than it was among ethanol-negative patients.",
            "output": [
                "Is ethanol-associated hypoglycemia uncommon?"
            ]
        },
        {
            "id": "task847-1c80770a38814a188626628c1dd11bfa",
            "input": "In amyotrophic lateral sclerosis (ALS), symptoms apparently spread following regional rules, and depending on the site of onset. We examined if respiratory function deterioration appears earlier or is more severe in patients with upper-limb onset.', 'We compared the results of various pulmonary function tests (PFT) obtained at diagnosis depending on the site of onset in 49 ALS patients. In a longitudinal study, we compared the deterioration of forced vital capacity (FVC) in relation to the site of onset, and analyzed the time elapsed to reach values below 80% of predicted according to site of onset, and we compared the survival depending on the site of onset.', 'No significant differences in PFT were found in the upper-limb onset group in any of the analysis performed. No differences in survival were detected in any disease onset group.",
            "output": [
                "Is respiratory function deterioration time-linked with upper-limb onset in amyotrophic lateral sclerosis?"
            ]
        },
        {
            "id": "task847-9d0dfb20fa254c3bb7db08366d853874",
            "input": "The quantity of the silver-stained nucleolar proteins (AgNOR proteins) measured in situ in cytohistologic preparations is related to the rapidity of cell proliferation. The term \"AgNOR proteins\" comprises several proteins. The relationship between the individual AgNOR protein amount and cell proliferating activity is not yet known. We studied the quantitative distribution of the individual AgNOR proteins, with specific attention to the two major AgNOR proteins, nucleolin and protein B23, in seven human cancer cell lines characterized by different cell doubling times.', 'The doubling time of cancer cells was measured by counting the asynchronously growing cells at regular time intervals. The AgNOR proteins were quantified in situ, after a specific one-step staining procedure, by computerized image analysis. For the quantitative evaluation of nucleolin and protein B23, two methods were followed. Nuclear proteins after separation by SDS-PAGE were transferred onto nitrocellulose membranes and were either: 1) stained by the silver staining procedure for AgNOR proteins or 2) treated with anti-nucleolin and anti-protein B23 mAb followed by reaction with secondary Ab linked to peroxidase and revealed by chemiluminescence and autoradiography. In both cases, measurement of individual AgNOR protein and nucleolin and protein B23 amount was carried out using computerized densitometric analysis.', 'Integrated density values of the silver-stained bands at 105 kDa (nucleolin) and 38 to 39 kDa (protein B23) represented, in all cell lines, more than 60% of the total silver-stained band value. A relationship was found between the densitometric values of silver-stained nucleolin and protein B23 and rapidity of cell proliferation (r = 0.85 and r = 0.86, respectively, p < 0.05). The values of nucleolin and protein B23 obtained using the Western blots were strictly related to the rapidity of cell proliferation (r = 0.93 and 0.96, respectively, p < 0.001). Finally, a good correlation was observed between the mean AgNOR protein area value, as defined in cytologic preparations in situ, and nucleolin and protein B23 amounts as evaluated in silver-stained nitrocellulose membranes (r = 0.92 and r = 0.90, respectively, p < 0.01) and in Western blots (r = 0.95 and r = 0.94, respectively, p < 0.001).",
            "output": [
                "Is the quantity of nucleolar proteins nucleolin and protein B23 related to cell doubling time in human cancer cells?"
            ]
        },
        {
            "id": "task847-ea999e9c423f423087ad84613664f903",
            "input": "The goal of this study was to identify factors that might aid in diagnosis and intraoperative management of hyperparathyroidism.', 'We analyzed biopsy specimens of 242 parathyroids from 159 patients by use of flow cytometry and image cytometry (ICM) for DNA index (DI), defined as the content of nuclear DNA compared with that expected for a DNA diploid standard, for proliferative index (PI), and for ploidy (diploid versus aneuploid or tetraploid).', 'True normal and normal parathyroids from patients with solitary adenomas were uniformly diploid. Abnormal ploidy (aneuploidy or tetraploidy) was identified frequently in adenomas and occasionally in hyperplasias with the exception that multiple endocrine neoplasia (MEN) biopsy specimens were uniformly diploid. DI for adenomas was similar to that for hyperplasias, and DI of both was higher than for normal glands. ICM-DI correlated positively with flow cytometry-DI and patient age and inversely with serum parathyroid hormone. PI was relatively low in all groups but was higher for hyperplasias versus normal parathyroids from patients with solitary adenomas and MEN versus non-MEN. PI correlated inversely with patient age.",
            "output": [
                "Do dNA index and ploidy distinguish normal human parathyroids from parathyroid adenomas and primary hyperplastic parathyroids?"
            ]
        },
        {
            "id": "task847-c5339e3bca6a43fdb11a492e662c3026",
            "input": "To determine the in vivo neutralizing activities of anti-interleukin-6 (IL-6) antibody on survival rate and host defense in a clinically relevant model of infection.', 'Prospective, randomized, experimental animal study.', 'University and Shriners Burns Institute research laboratories.', 'Two hundred seventy-six adult, female Balb/c mice.', 'Balb/c mice were treated with 10 micrograms of antimurine IL-6 antibody, nonspecific murine immunoglobulin G (IgG), or placebo at 2, 4, or 8 hrs after they underwent bacterial challenge by gavage of 10(10) Escherichia coli and thermal injury. The survival rate was determined. The number of viable translocated bacteria, the total amount of translocation, and the percentage of bacteria that survived were also studied in different tissues.', 'Survival rate after burn and gavage was significantly improved in animals treated with antimurine IL-6 antibody at 2 and 4 hrs but not at 8 hrs after injury compared with control animals treated with nonspecific IgG or saline. The IL-6 serum concentration was significantly lower after burn and gavage in the animals treated 2 and 4 hrs after injury compared with nontreated animals. Better killing of translocated bacteria was observed in the tissues of animals treated with antimurine IL-6 antibody 2 hrs after injury.",
            "output": [
                "Does anti-interleukin-6 antibody treatment improve survival during gut-derived sepsis in a time-dependent manner by enhancing host defense?"
            ]
        },
        {
            "id": "task847-320b2d4088404e14a3cafaa3752a5069",
            "input": "An accurate measure of the severity of ischemic insult and the resulting prognosis is needed to assess the effectiveness of new treatments for acute stroke. We studied the reproducibility and accuracy of measurements of infarct volume with MRI and correlated the measurements with outcome.', 'Infarct volume was measured on T2-weighted images with the Analyze image analysis software. This technique was found to be highly accurate and reproducible.', 'Measurements of infarct volume were found to be highly accurate and reproducible. Twenty-one patients (mean age, 66.5 years; range, 28 to 90 years) with cortical middle cerebral artery territory infarcts in whom adequate data could be obtained were studied within 72 hours from onset (mean delay to MRI, 27.5 hours; range, 5 to 72 hours). The Scandinavian Stroke Scale was used to calculate a prognostic score, and clinical outcome was assessed at 3 months. Infarct volume was found to significantly predict outcome. Mean infarct volume in the independent patients was 35.7 +/- 29.7 cm3 compared with 88.3 +/- 71.3 cm3 in dependent patients and 166.5 +/- 65.9 cm3 in dead patients (F = 10.52, P < .001). Patients with an initial infarct volume less than 80 cm3 were found to have a better outcome than those with larger infarct volumes. Secondary hemorrhage visible on MRI also predicted a poor outcome. In contrast, the Scandinavian Stroke Scale did not significantly predict outcome.",
            "output": [
                "Does measurement of infarct size using MRI predict prognosis in middle cerebral artery infarction?"
            ]
        },
        {
            "id": "task847-23d609f045574e85963864fa2c13a11a",
            "input": "To evaluate the concordance between thallium-201 uptake and echocardiographic wall thickening, which are both indicators of potentially reversible myocardial dysfunction, in patients with chronic ischaemic left ventricular failure and to assess their relative contribution to predicting improvement in regional function after revascularisation in a subgroup.', '45 patients with chronic ischaemic left ventricular dysfunction (mean (SD) ejection fraction 25 (8)%) underwent echocardiography before and after dobutamine infusion (10 micrograms/kg/min). Of these, 22 patients underwent rest echocardiography at a mean (SD) of 9 (1) weeks after revascularisation. 201Tl imaging was performed during dobutamine echocardiography and at rest, 1, and 4 h after treatment with sublingual glyceryl trinitrate on two separate days. Potentially reversible dysfunction was thought to be present when a myocardial segment contained a Tl score of > or = 3 (ascending score 1-4), or showed improved wall thickening of a dysynergic segment during dobutamine stimulation.', 'Of the 201Tl protocols, the redistribution scan 1 h after treatment with glyceryl trinitrate best demonstrated myocardial viability. Concordance between 201Tl and dobutamine induced wall thickening was 82% (kappa = 0.59) for detecting potentially reversible myocardial dysfunction before revascularisation (n = 45). Regional function improved in 18 of 22 patients after revascularisation. There were 168 dysynergic segments before intervention. The sensitivity of echocardiography and 201Tl imaging for detecting \"recoverable\" or viable segments after revascularisation was 87% and 92% respectively and specificity was 82% and 78% respectively (P = NS).",
            "output": [
                "Do dobutamine echocardiography and thallium-201 imaging predict functional improvement after revascularisation in severe ischaemic left ventricular dysfunction?"
            ]
        },
        {
            "id": "task847-2666828f681d4a5d89486396f42ec324",
            "input": "To examine the association between serum lipoprotein(a) and angiographically assessed coronary artery disease progression without new myocardial infarction.', '85 patients with coronary artery disease who underwent serial angiography with an interval of at least two years were studied. Progression of coronary artery disease was defined as an increase in diameter stenosis of 15% or more. Vessels on which angioplasty had been performed were excluded from the analysis. The patients were classified into two groups: a progression group without new myocardial infarction (n = 48) and non-progression group (n = 37). Risk factors including lipoprotein(a) were evaluated to see how they were related to progression without myocardial infarction.', 'There were no differences between the two groups in the following factors: age, gender, the time interval between the angiographic studies, the distribution of the analysed coronary arteries, and history of well established coronary risk factors. Univariate analysis showed that serum lipoprotein(a) (P = 0.0002), cigarette smoking between the studies (P = 0.002), serum high density lipoprotein (P = 0.003), and serum low density lipoprotein (P = 0.01) were related to progression without myocardial infarction. Multivariate analysis selected two independent factors for progression without myocardial infarction: serum lipoprotein(a) (P = 0.003) and serum high density lipoprotein (P = 0.03).",
            "output": [
                "Are serum lipoprotein ( a ) concentrations related to coronary disease progression without new myocardial infarction?"
            ]
        },
        {
            "id": "task847-b426c4cad0254f54971f0d4090a6fb07",
            "input": "This study reports on an extremely rare case of tuberculous psoas abscess and describes the mode of diagnosis and treatment.', 'This patient is presented to emphasize that cases of solitary psoas abscess resulting from tuberculosis exist today.', \"No recent cases of latent solitary tuberculous psoas abscess have been reported, to the authors' knowledge.\", 'A tuberculous psoas abscess associated with fistula to the greater trochanter may remain dormant for years after tuberculous spondylitis has healed, as a distinct entity without concomitant active bone infection. In our 58-year-old female patient, the diagnosis of a psoas abscess was greatly aided by the \"three pass\" technetium bone scan and computed tomography, but the anamnesis also was important.', 'Anti-tuberculosis medication (streptomycin, aminosalicylic, and isoniazid) combined with open drainage, curettage of the psoas, and simultaneous revision of the fistula eradicated the disease, making the course of the disease uneventful until the 5-year follow-up evaluation.",
            "output": [
                "Do latent solitary tuberculous psoas abscess 52 years after healed thoracolumbar tuberculous spondylitis?"
            ]
        },
        {
            "id": "task847-25698dcd6c444782a3d38168eb4d5117",
            "input": "We previously reported that the intimal endothelium of the rat aorta switches to a microvascular phenotype during angiogenesis in vitro. The microvessels formed by the rat aortic endothelium are coated with pericytes. The purpose of this study was to evaluate the relation of the pericytes to the angiogenic process and to identify the site of origin of these cells in the aortic wall.', 'Rings of rat aorta were cultured in collagen gel under serum-free conditions. The formation of a pericyte coating around aorta-derived microvessels was evaluated by counting pericytes and microvessels in the living cultures. Pericytes and endothelial cells were studied by immunohistochemistry, lectin labeling, electron microscopy, 3H-thymidine labeling followed by autoradiography, and time-lapse video microscopy. The capacity of aortic smooth muscle cells to differentiate into pericytes was studied by coculturing intimal- or medial-derived smooth muscle cells with endothelial cells in a collagen gel overlay assay that induced reorganization of endothelial cells into microvessels.', 'Microvessels during the early stages of angiogenesis were composed primarily of endothelial cells. As vascular proliferation decreased, the microvessels became coated with pericytes. The pericytes migrated from the root to the tip of the microvessels using the endothelium as a surface for attachment, proliferation, and contact guidance. The pericytes were continuous with the myointimal endothelial cells of the cultured aorta. Pericytes and myointimal cells were positive for alpha-smooth muscle actin and vimentin and were actively engaged in DNA synthesis. Treatment of the cultures with heparin caused a marked reduction in the number of pericytes. Smooth muscle cells isolated from the intimal aspect of the rat aorta migrated toward the endothelium and differentiated into pericytes when cocultured with microvessels formed by isolated endothelial cells in a collagen gel overlay assay. Conversely, smooth muscle cells isolated from the deep layers of the media had no significant endothelial tropism and failed to differentiate into pericytes.",
            "output": [
                "Do rat aortic smooth muscle cells become pericytes during angiogenesis in vitro?"
            ]
        },
        {
            "id": "task847-aa46bcaa1433467f990f95294e376398",
            "input": "Bilateral lower extremity venous duplex scanning for acute deep venous thrombosis (DVT) has been advocated because of the high incidence of occult contralateral leg involvement. We investigated the clinical necessity of such a policy.', 'The results from 2996 venous duplex studies performed during the past 2 years were retrospectively reviewed. A total of 1694 of these scans were performed on patients with symptoms, of whom 248 (15%) were found to have an acute DVT. Symptoms were limited to one side in 198 patients, whereas bilateral complaints were noted in 50 patients.', 'Among the patients with symptoms of acute DVT, 72 (29%) had bilateral involvement. Bilaterality was more likely in patients with bilateral symptoms than in those with only unilateral symptoms (56% vs 22%; p < 0.005). Of the patients with unilateral symptoms and bilateral DVT, all of them had either acute (80%) or acute and chronic (20%) thrombosis in the symptomatic leg. The contralateral asymptomatic limb had fewer acute and more chronic DVT (41% and 55%, respectively). No patient from the entire group admitted with symptoms had an acute DVT in the asymptomatic limb without a concomitant acute DVT in the symptomatic leg. Unilateral scanning would decrease the examination time by 21% and potentially increase total reimbursement for symptomatic venous scans by 9% compared with routine bilateral duplex scanning.",
            "output": [
                "Is contralateral duplex scanning for deep venous thrombosis unnecessary in patients with symptoms?"
            ]
        },
        {
            "id": "task847-98c53b2dfb4a4aefaec2aef9a7904430",
            "input": "Hyperbaric oxygen (HBO) has been advocated as a therapy to improve neurological recovery after ischemia, since HBO may improve tissue oxygen delivery. We examined the effect of HBO treatment after global cerebral ischemia on early brain injury.', 'Rabbits were subjected to 10 minutes of global cerebral ischemia by cerebrospinal fluid compression. After 30 minutes of reperfusion, rabbits either were subjected to HBO for 125 minutes and then breathed 100% O2 at ambient pressure for 90 minutes or breathed 100% O2 for 215 minutes. At the end of reperfusion and 90 minutes after exposure, brain vascular permeability and cerebral blood flow were measured. Somatosensory evoked potentials were monitored throughout the experiment.', 'HBO treatment reduced (P < .05) brain vascular permeability by 16% in gray matter and by 20% in white matter. Cerebral blood flow was lower (P < .05) in the HBO group (40.9 +/- 1.9 mL/min per 100 g, mean +/- SEM) compared with controls (50.8 +/- 2.0 mL/min per 100 g). Somatosensory evoked potential recovery was similar in the two groups (P > .05).",
            "output": [
                "Does hyperbaric oxygen after global cerebral ischemia in rabbits reduce brain vascular permeability and blood flow?"
            ]
        },
        {
            "id": "task847-1ac3a2f5296f40329546f6e4dd640a05",
            "input": "The cutaneous microcirculation vasodilates during acute 6 degrees head-down tilt (HDT, simulated microgravity) relative to upright conditions, more in the lower body than in the upper body.', 'We expected that relative magnitudes of and differences between upper and lower body cutaneous blood flow elevation would be sustained during initial acclimation to simulated microgravity.', 'We measured cutaneous microvascular blood flow with laser-Doppler flowmetry at the leg (over the distal tibia) and cheek (over the zygomatic arch) of eight healthy men before, during, and after 24 h of HDT. Results were calculated as a percentage of baseline value (100% measured during pre-tilt upright sitting).', 'Cutaneous blood flow in the cheek increased significantly to 165 +/- 37% (mean +/- SE, p < 0.05) at 9-12 h HDT, then returned to near baseline values by 24 h HDT (114 +/- 29%, NSD), despite increased local arterial pressure. Microvascular flow in the leg remained significantly elevated above baseline throughout 24 h HDT (427 +/- 85% at 3 h HDT and 215 +/- 142% at 24 h HDT, p < 0.05). During the 6-h upright sitting recovery period, cheek and leg blood flow levels returned to near pre-tilt baseline values.",
            "output": [
                "Does simulated microgravity increase cutaneous blood flow in the head and leg of humans?"
            ]
        },
        {
            "id": "task847-22c54bfa966a4ceaad8e687a535b2653",
            "input": "A substantial number of patients who elect to undergo photorefractive keratectomy do so without the motivation of occupational uncorrected vision requirements. We hypothesized that information processing preferences for the auditory (versus visual) modality in a global, associative (versus detailed, sensory-oriented) style with adaptability and risk-taking (versus predictability) personality characteristics would predominate in patients electing photorefractive keratectomy.', 'Seventy-three prospective photorefractive keratectomy patients attended informational sessions. Sixteen occupationally driven patients and one refusal were excluded from the analysis. The 27 patients electing to proceed with surgery were compared with the 29 declining surgery. Personality characteristics and cognitive styles were determined by the Myers-Briggs Type Indicator: Abbreviated Version and the Modality Strengths Indicator.', 'Subjects electing surgery showed significantly greater preferences for processing information in the auditory modality and in a global, associative style, with adaptability and risk-taking personality characteristics. Combining the attributes statistically differentiated the two groups.",
            "output": [
                "Do cognitive styles and personality characteristics strongly influence the decision to have photorefractive keratectomy?"
            ]
        },
        {
            "id": "task847-2df0d77a25cb47bca012c31fe2969e01",
            "input": "To investigate the significance of respiratory muscle weakness in chronic heart failure and its relation both to maximum oxygen consumption during cardiopulmonary exercise testing and to skeletal muscle (quadriceps) strength.', 'Seven healthy men aged 54.9 (SEM 4.3) years and 20 men with chronic heart failure aged 61.4 (1.6) years (P = 0.20) with radionuclide left ventricular ejection fraction of 25.4 (3.0)%.', 'Mouth pressures during maximum static inspiratory effort (PImax) at functional residual capacity (FRC) and residual volume (RV) were measured in all subjects and taken as indices of inspiratory muscle strength. Similarly, mouth pressures during maximum static expiratory effort (PEmax) at FRC and total lung capacity (TLC) were taken as indices of expiratory muscle strength. Cardiopulmonary exercise testing was performed in all subjects. All controls and 15 heart failure patients also had their right quadriceps muscle strength measured.', 'There was respiratory muscle weakness in heart failure patients, with reduction of PImax at FRC (59.7) (6.3) v 85.6 (9.6) cm H2O, P = 0.045), PEmax at FRC (94.8 (6.2) v 134.6 (9.1) cm H2O, P = 0.004), and PEmax at TLC (121.7 (8.5) v 160.7 (13) cm H2O, P = 0.028). PImax at RV was also reduced but this did not reach statistical significance (77.3 (6.6) v 89.3 (13) cm H2O, P = 0.44). There was also significant weakness of the right quadriceps muscle (308.5 (22) v 446.2 (28) N, P = 0.001). PImax at both FRC and RV correlated with maximum oxygen consumption (r = 0.59, P = 0.006, and r = 0.45, P = 0.048 respectively) but not PEmax. There was, however, no significant correlation between PImax and right quadriceps strength.",
            "output": [
                "Is inspiratory muscle strength a determinant of maximum oxygen consumption in chronic heart failure?"
            ]
        },
        {
            "id": "task847-f1f98af2f7ec47a292e021536b177d24",
            "input": "At birth the fetus emerges from a sterile environment into a nonsterile one. This process is associated with activation of the fetal immune system which protects the fetus against infection in the newborn period. We conducted this study to determine whether activation of the monocyte-neutrophil system occurs in fetuses before premature birth.', 'Forty patients in premature labor with intact membranes underwent cordocentesis for research purposes. Fetal blood was analyzed with the use of flow cytometry to measure the cell surface markers CD11c, CD13, CD15, and CD67, which are associated with monocyte and neutrophil activation, and CD14 and CD63, which were used as controls.', 'Twenty-eight percent (11/40) of the infants were delivered prematurely within 72 hours of entering the study while the remainder were delivered at term. Our data clearly indicate that premature infants delivered within 72 hours had a higher percentage of CD11c, CD13, CD15, and CD67 than those delivered at term. In contrast, there were no significant differences in the percentages of CD14 and CD63.",
            "output": [
                "Is premature parturition characterized by in utero activation of the fetal immune system?"
            ]
        },
        {
            "id": "task847-b19ae1a5744045f0b3ab1602337efa20",
            "input": "Our prior studies show that intravenous (IV) total parenteral nutrition (TPN) produces atrophy of the small intestine-related gut-associated lymphoid tissue and significant decreases in intestinal IgA levels, the major system of mucosal immunity. Others have noted increased small intestinal permeability, bacterial adherence and translocation, and decreased IgA levels in TPN-fed animals. Bombesin, a neuropeptide, may play a regulatory role in mucosal immunity. It is not clear whether bombesin attenuates the TPN-associated gut-associated lymphoid tissue atrophy.', 'To examine the effect of bombesin on gut-associated lymphoid tissue integrity and function during IV TPN feeding.', 'Randomized animal study.', 'A university laboratory.', \"Male ICR mice weighing 25 to 30 g were randomized to chow plus IV saline solution (n = 12), IV TPN (n = 12), or IV TPN plus bombesin (15 micrograms/kg, administered intramuscularly three times a day) (n = 12). Animals were killed after 5 days of receiving the experimental diet. Total small intestinal IgA level was quantified by enzyme-linked immunosorbent assay. Lymphocytes were isolated from Peyer's patches, intraepithelial spaces, and lamina propria and were stained with specific antibodies for B and T cells and for T-cell expression of CD4 and CD8 by flow cytometric analysis. Data were analyzed by analysis of variance.\", \"Bombesin prevented the IV TPN decreases in (1) total cell yield and B-cell yield from the Peyer's patches, intraepithelial spaces, and lamina propria; (2) T-cell yield in the intraepithelial spaces and lamina propria; and (3) small intestinal IgA levels. Bombesin also reversed IV TPN decreases in CD4+ and CD8+ T cells in the intraepithelial spaces and Peyer's patches and prevented the decrease in the CD4/CD8 ratio in the lamina propria.",
            "output": [
                "Does bombesin affect mucosal immunity and gut-associated lymphoid tissue in intravenously fed mice?"
            ]
        },
        {
            "id": "task847-39681c23c5174c039a0d1052cb45ca11",
            "input": "To assess any relationship between hyperglycemia and muscle protein catabolism associated with critical illness.', 'Cohort analytic study.', 'Clinical research center and intensive care unit of a university hospital.', 'Six healthy volunteers and five patients with severe sepsis.', 'Study subjects were given infusions of 6,6,d2 glucose and 15N lysine for 6 hours. After infusion of the stable isotopes for 2 hours (basal period), dichloroacetate, which accelerates pyruvate oxidation, was given (dichloroacetate period). Leg blood flow was measured by indocyanine green dye dilution, and femoral artery and vein substrate concentrations were quantitated.', 'The metabolic rates of glucose production, oxidation, and clearance; the whole-body protein breakdown rate; and the net efflux of amino acids from the leg were determined.', 'In comparison with the healthy volunteers, septic patients had significant elevations in glucose production, oxidation, and clearance, accelerated protein catabolism, and greater net peripheral efflux of amino acids. Dichloroacetate significantly decreased glucose production and increased the percentage of glucose directed toward oxidation in both healthy volunteers and septic patients. However, this dichloroacetate-induced perturbation of glucose utilization had no significant effect on whole-body protein breakdown or the efflux of specific amino acids from the leg except for alanine, whose net efflux doubled (P < or = .05).",
            "output": [
                "Is except for alanine , muscle protein catabolism influenced by alterations in glucose metabolism during sepsis?"
            ]
        },
        {
            "id": "task847-29896c7298ee4f14938920f67043fdea",
            "input": "To describe the differences in health behaviours in disparate marital status groups and to estimate the extent to which these can explain differences in health associated with marital status.', 'Baseline data of a prospective cohort study were used. Directly age standardised percentages of each marital group that engaged in each of the following behaviours--smoking, alcohol consumption, coffee consumption, breakfast, leisure exercise, and body mass index--were computed. Multiple logistic regression models were fitted to estimate the health differences associated with marital status with and without control for differences in health behaviours.', 'The population of the city of Eindhoven and surrounding municipalities (mixed urban-rural area) in The Netherlands in March 1991.', 'There were 16,311 men and women, aged 25-74 years, and of Dutch nationality.', 'There were differences in relation to marital status for each health behaviour. Married people were more likely to practise positive health behaviours (such as exercise and eating breakfast) and less likely to engage in negative ones (such as smoking or drinking heavily) than the other groups. Control for all six health behaviours could explain an average of 20-36% of the differences in perceived and general health and subjective health complaints.",
            "output": [
                "Do health behaviours explain part of the differences in self reported health associated with partner/marital status in The Netherlands?"
            ]
        },
        {
            "id": "task847-1c86129f7c6f4c1e9bdb9009290eba2c",
            "input": "Vancomycin is effective in reducing the risk of mediastinits and topical vancomycin has been hypothesised to give high local dose concentrations while avoiding high systemic levels, thus avoiding the risk of bacterial resistance to this second-line antibiotic. However, this theory has never been tested and the degree to which vancomycin is absorbed systemically is unknown.', 'Fourteen patients undergoing elective coronary artery bypass grafts (CABG) received 500mg of topical vancomycin prior to sternotomy closure. Serum samples were taken at 30, 60, 120, 180 and 720min post-operatively. In addition, samples were taken from the drain bottles and urine samples taken daily for 5 days. Vancomycin levels were measured by fluorescence polarisation immunoassay, using the reverse dilution method to give a detection limit of 0.8mg/l.', 'Vancomycin was detected in almost all serum samples. Peak concentration was at 30min and the mean value was 2.96mg/l (range, 0.99-5.00mg/l). This mean fell to 1.32mg/l at 6h. Of the 500mg of vancomycin applied, a mean of only 8.8mg was found to have been lost into the drain bottles in the first 24h (range, 0.17-12.5mg). When 5 consecutive days of urine collection was achieved, a mean of 151mg of vancomycin was excreted (range, 40-195mg) and vancomycin was detectable in the urine till day 5. The mean concentration of vancomycin in the urine was maximal on day 1 and was 24.4mg/l (range, 4.49-44.98mg/l).",
            "output": [
                "Does topical vancomycin applied on closure of the sternotomy wound prevent high levels of systemic vancomycin?"
            ]
        },
        {
            "id": "task847-0a9bedb6d8764b47bcc5f9d1c8655dd1",
            "input": "This study was designed to determine the relevance of a proposed classification for advanced heart failure (HF). Profiles based on clinical assessment of congestion and perfusion at the time of hospitalization were compared with subsequent outcomes.', 'Optimal design of therapy and trials for advanced HF remains limited by the lack of simple clinical profiles to characterize patients.', \"Prospective analysis was performed for 452 patients admitted to the cardiomyopathy service at the Brigham and Women's Hospital with a diagnosis of HF. Patients were classified by clinical assessment into four profiles: profile A, patients with no evidence of congestion or hypoperfusion (dry-warm, n = 123); profile B, congestion with adequate perfusion (wet-warm, n = 222); profile C, congestion and hypoperfusion (wet-cold, n = 91); and profile L, hypoperfusion without congestion (dry-cold, n = 16). Other standard predictors of outcome were included and patients were followed for the end points of death (n = 117) and death or urgent transplantation (n = 137) at one year.\", 'Survival analysis showed that clinical profiles predict outcomes in HF. Profiles B and C increase the risk of death plus urgent transplantation by univariate (hazard ratio [HR] 1.83, p = 0.02) and multivariate analyses (HR 2.48, p = 0.003). Moreover, clinical profiles add prognostic information even when limited to patients with New York Heart Association (NYHA) class III/IV symptoms (profile B: HR 2.23, p = 0.026; profile C: HR 2.73, p = 0.009).",
            "output": [
                "Does clinical assessment identify hemodynamic profiles that predict outcomes in patients admitted with heart failure?"
            ]
        },
        {
            "id": "task847-c3a311a9746b4959907828080d18fd2d",
            "input": "We investigated cardiac energetics in subjects with mutations in three different familial hypertrophic cardiomyopathy (HCM) disease genes, some of whom were nonpenetrant carriers without hypertrophy, using phosphorus-31 magnetic resonance spectroscopy.', 'Familial hypertrophic cardiomyopathy is caused by mutations in sarcomeric protein genes. The mechanism by which these mutant proteins cause disease is uncertain. A defect of myocyte contractility had been proposed, but in vitro studies of force generation have subsequently shown opposing results in different classes of mutation. An alternative hypothesis of \"energy compromise\" resulting from inefficient utilization of adenosine triphosphate (ATP) has been suggested, but in vivo data in humans with genotyped HCM are lacking.', 'The cardiac phosphocreatine (PCr) to ATP ratio was determined at rest in 31 patients harboring mutations in the genes for either beta-myosin heavy chain, cardiac troponin T, or myosin-binding protein C, and in 24 controls. Transthoracic echocardiography was used to measure left ventricular (LV) dimensions and maximal wall thickness.', 'The PCr/ATP was reduced in the HCM subjects by 30% relative to controls (1.70 +/- 0.43 vs. 2.44 +/- 0.30; p < 0.001), and the reduction was of a similar magnitude in all three disease-gene groups. The PCr/ATP was equally reduced in subjects with (n = 24) and without (n = 7) LV hypertrophy.",
            "output": [
                "Is hypertrophic cardiomyopathy due to sarcomeric gene mutations characterized by impaired energy metabolism irrespective of the degree of hypertrophy?"
            ]
        },
        {
            "id": "task847-9c97da71deab43fc83cac5fd9b0a28ae",
            "input": "We investigated the usefulness of central retinal artery (CRA) Doppler flowmetry in patients with cerebral small-vessel disease (SVD).', 'CRA Doppler flowmetry was performed in 103 SVD patients who underwent MRI. Sixty-four adjusted control subjects were also registered. We assessed average CRA flow parameter values for both eyes with the clinical and MRI findings.', 'Each Doppler flowmetry was performed within 5 minutes. Patients with SVD had significantly lower end-diastolic and mean velocities of the CRA than control subjects; they also had higher pulsatility and resistive indexes. Multivariate analysis showed that the number of small infarcts was an independent predictor of peak systolic and mean velocities. Grade of periventricular hyperintensities was an additional independent predictor of peak systolic and mean velocities, whereas the number of small infarcts was predictive of end-diastolic velocity.",
            "output": [
                "Do central retinal artery Doppler flow parameters reflect the severity of cerebral small-vessel disease?"
            ]
        },
        {
            "id": "task847-591d83b1232045a6983212126402d3a8",
            "input": "A 6-base insertion (6bINS) polymorphism in intron 7 of the endoglin gene (ENG), which codes for a component of the transforming growth factor-beta receptor complex, was reported to be associated with intracranial aneurysm (IA) in a Japanese population. A recent report using a white population could not replicate the association. We tested for this association with high statistical power in our independent Japanese subjects and evaluated the linkage between markers on chromosome 9, which contains ENG, and IA.', 'The sample for the linkage study comprised 179 individuals with IA in 85 nuclear families, with 104 possible affected sibpairs. For the association study of the 6bINS polymorphism and 4 single nucleotide polymorphisms (SNPs) in ENG, 172 Japanese patients with IA and 192 control subjects were examined.', 'There was no evidence of linkage in the vicinity of ENG by analysis of affected sibpairs. The allele frequency of the 6bINS polymorphism was 104 of 344 (30.2%) in the total IA group and 122 of 382 (31.9%) in the control group. The statistical difference in allele frequency between the 2 groups was not significant (chi2=0.245, df=1, P=0.620). The power of the present association study was 98.3% at a significance level of 0.05 on the basis of the allele frequencies in the previous study. In addition, no associations between the 4 SNPs in ENG and IA were detected.",
            "output": [
                "Is endoglin a major susceptibility gene for intracranial aneurysm among Japanese?"
            ]
        },
        {
            "id": "task847-988b665c215542fc9a0d2ab609140c0b",
            "input": "Hand warming and face warming, combined with inhalation of heated air, are reported to suppress shivering. However, hand or face temperature contributes only a few percent to control of shivering. Thus, it seems unlikely that manipulating hand or facial skin temperature alone would be sufficient to permit induction of therapeutic hypothermia. We tested the hypothesis that focal arm (forearm and hand) warming or lower facial warming, combined with inhalation of heated and humidified gas, only minimally reduces the shivering threshold (triggering core temperature).', 'We studied 8 healthy male volunteers (18 to 40 years of age) on 3 days: (1) control (no warming), (2) arm warming with forced air at approximately 43 degrees C, and (3) face warming with 21 L/min of air at approximately 42 degrees C at a relative humidity of 100%. Fluid at approximately 4 degrees C was infused via a central venous catheter to decrease tympanic membrane temperature 1 degrees C/h to 2 degrees C/h; mean skin temperature was maintained at 31 degrees C. A sustained increase in oxygen consumption quantified the shivering threshold.', 'Shivering thresholds did not differ significantly between the control (36.7+/-0.1 degrees C), arm-warming (36.5+/-0.3 degrees C), or face-warming (36.5+/-0.3 degrees C; analysis of variance, P=0.34) day. The study was powered to have a 95% probability of detecting a difference of 0.5+/-0.5 degrees C (mean+/-SD) between control and either of the 2 treatments at alpha=0.05.",
            "output": [
                "Does neither arm nor face warming reduce the shivering threshold in unanesthetized humans?"
            ]
        },
        {
            "id": "task847-682b78d9e0d9480eb48380cca0c26278",
            "input": "For approximately 5% of autologous transplant recipients and a higher proportion of allogeneic transplant recipients, low level and delayed platelet engraftment is an ongoing problem. Mesenchymal stem cells (MSC), which can be derived from bone marrow as well as other organs, are capable of differentiation into multiple cell types and also support hematopoiesis in vitro. Because cotransplantation of marrow-derived stromal cells has been shown to enhance engraftment of human hematopoietic stem cells, we hypothesized that cotransplantation of MSC could enhance platelet and myeloid cell development.', 'We tested this hypothesis by transplantation of CD34-selected mobilized human peripheral blood stem cells (PBSC) into sublethally irradiated NOD/SCID mice with or without culture-expanded human MSC and evaluated human myeloid, lymphoid, and megakaryocytic engraftment with flow cytometry and in vitro cultures.', 'We find that MSC cotransplantation enhances human cell engraftment when a limiting dose (<1 x 10(6)) of CD34 cells is administered. This enhancement is characterized by a shift in the differentiation of human cells from predominantly B lymphocytes to predominantly CD13(+), CD14(+), and CD33(+) myeloid cells with a corresponding increase in myeloid CFU in the marrow. Megakaryocytopoiesis is enhanced by MSC cotransplantation as assessed by an increase in both marrow CFU-MK and circulating human platelets. In contrast, MSC do not affect the percentage of human bone marrow cells that expresses CD34(+).",
            "output": [
                "Does cotransplantation of human mesenchymal stem cells enhance human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice?"
            ]
        },
        {
            "id": "task847-3fd2f8da766146bf8024f7db838d8e5f",
            "input": "The assessment of outcome in schizophrenic patients should consider both the response to treatment and the recovery of social skills. The aim was to evaluate the outcome and related psychostructural and clinical factors in schizophrenic patients after they underwent 6 months of residential multimodal treatment.', 'Fifty-two schizophrenic patients enrolled in a multimodal treatment program were included in the study. Symptomatology and social functioning were assessed with the Brief Psychiatric Rating Scale (BPRS) and the Social and Occupational Functioning Assessment Scale (SOFAS). The Karolinska Psychodynamic Profile (KAPP) was used for the psychostructural evaluation.', 'After 6 months there was a significant improvement in the global scores of BPRS, SOFAS, and some areas of KAPP. The personality (KAPP) and social-occupational functioning (SOFAS) at baseline (T0) correlated with the global score of BPRS at 6 months (T6); moreover, SOFAS at T6 correlated with BPRS and KAPP at T0 and with the illness duration.",
            "output": [
                "Does baseline personality functioning correlate with 6 month outcome in schizophrenia?"
            ]
        },
        {
            "id": "task847-9d80bb5555f54d1c9c8402f4831007ea",
            "input": "Airway hyperresponsiveness (AHR) is associated with persistent air flow limitation and accelerated FEV(1) decline. AHR can influence diagnosis, treatment, and prognosis. We assessed the value of pulmonary function variables, symptoms, and history as selection criteria for methacholine bronchoprovocation testing to detect AHR in symptomatic subjects.', 'Over a 4-year period we conducted a prospective study of consecutive subjects who underwent methacholine bronchoprovocation testing. Baseline pulmonary function testing (PFT) and a questionnaire were obtained prior to methacholine bronchoprovocation testing. PFT and symptom and history variables were assessed as AHR predictors in univariate and multiple logistic regression analyses for the whole group and for 4 different age groups.', 'There were 530 subjects, with ages ranging from 5 to 87 years, and 232 (44%) were positive for methacholine AHR. AHR was more prevalent among subjects < or = 25 years old (59%) and > 65 years old (47%) than among the other age groups. PFT values, symptom, and history variables had different AHR predictive values among the different age groups. Symptom and history variables had no AHR predictive value among subjects < or = 25 or > 65 years old.",
            "output": [
                "Are clinical variables poor selection criteria for the use of methacholine bronchoprovocation in symptomatic subjects?"
            ]
        },
        {
            "id": "task847-402ec207eb784ce49d1dde63b22f64b0",
            "input": "We were interested in exploring the molecular mechanisms underlying the observed difference in histamine (H) responsiveness between seasonal allergic rhinitic (SAR) and nonrhinitic (NR) subjects. We hypothesized that SAR subjects express higher nasal mucosal histamine receptor 1 (H1R) and 2 (H2R) levels than do NR subjects. In addition, we examined expression of genes involved in regulating the glandular response, including epidermal growth factor (EGF), EGF receptor (EGFR), and mucins (Muc5Ac and Muc5B).', 'Fourteen subjects, seven SAR and seven NR, were provoked during pollen season with doubling doses of H (0.125-8.0 mg/ml). Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Provocation was halted when NAR exceeded 150% of baseline. Prior to provocation, nasal scrapings were obtained and mRNA quantified using two-step real-time PCR.', 'The mean PD50 (concentration of H producing a 50% increase in NAR) was significantly lower in the SAR than NR group (0.36 vs 1.32 mg/ml; P < 0.05). The ratio of relative gene copy numbers between the SAR and NR groups were as follows: H1R, 0.85 (P = 0.52); H2R, 0.67 (P = 0.35); EGF, 1.02 (P = 0.93), and EGFR, 103.5 (P < 0.05).",
            "output": [
                "Is epidermal growth factor receptor - but not histamine receptor - upregulated in seasonal allergic rhinitis?"
            ]
        },
        {
            "id": "task847-7adb7fecc146498d9b0b691b8b7b0ba9",
            "input": "Postoperative neurologic deficits after thoracic aortic reconstruction vary widely. Our previous study showed that delayed ischemic preconditioning could prevent spinal cord injury caused by occlusion of the descending thoracic aorta in pigs. We investigated early ischemic preconditioning in the same model.', 'Twenty-eight pigs were divided into 4 groups: group 1 (n = 6) underwent a sham operation, group 2 (n = 6) underwent aortic occlusion for 20 minutes, group 3 (n = 8) underwent aortic occlusion for 35 minutes, and group 4 (n = 8) underwent aortic occlusion for 20 minutes and underwent aortic occlusion 80 minutes later without hypotension for 35 minutes. Aortic occlusion was accomplished by using 2 balloon occlusion catheters placed fluoroscopically at T6 to T8 above the diaphragm and at the aortic bifurcation. Neurologic evaluation was performed by an independent observer according to the Tarlov scale (0-4). The lower thoracic and lumbar spinal cords were harvested at 120 hours and examined histologically with hematoxylin-and-eosin stain. Histologic results (number of neurons and grade of inflammation) were scored (0-4) and were similarly analyzed. Statistical analysis was by means of the Kruskal-Wallis test.', 'Group 4 had a better neurologic outcome at 24, 48, and 120 hours in comparison with group 3 (P <.001). The histologic changes were proportional to the neurologic test scores, with the more severe and extensive gray matter damage in animals of group 3 (number of neurons, P <.001; grade of inflammation, P <.001).",
            "output": [
                "Does early ischemic preconditioning without hypotension prevent spinal cord injury caused by descending thoracic aortic occlusion?"
            ]
        },
        {
            "id": "task847-0424457b00ab448e9ae84c1bfa16ddcc",
            "input": "This experimental study was undertaken to determine whether pretreatment with statins would enhance myocardial protection and minimize ischemic injury during revascularization of acutely ischemic myocardium.', 'In 20 pigs the second and third diagonal arteries were occluded for 90 minutes, followed by 45 minutes of blood cardioplegic arrest and 180 minutes of reperfusion. Ten pigs received atorvastatin (40 mg orally every day) for 21 days before surgical intervention; 10 others received no statins. Ischemic damage was assessed on the basis of the need for cardioversions for ventricular arrhythmias, regional wall-motion scores (4 = normal to -1 = dyskinesia) were determined by means of 2-dimensional echocardiography, endothelial function was assessed on the basis of bradykinin-induced coronary artery relaxation, and infarct size was calculated by determining the area of necrosis to the area of risk by means of histochemical staining. Results are given as means +/- SE.', 'Statin-treated animals required fewer cardioversions (0.11 +/- 0.01 vs 2.87 +/- 0.20, P =.0001), had improved wall-motion scores (2.81 +/- 0.10 vs 1.52 +/- 0.08, P =.01), had lower infarct size (21% +/- 2% vs 41% +/- 2%, P =.0001), and had more complete coronary artery relaxation (34% +/- 5% vs 8% +/- 4%, P =.01). Total serum cholesterol levels were similar between the groups (62 +/- 5 mg/dL for statin-treated animals vs 68 +/- 5 mg/dL for non-statin-treated animals, P =.30).",
            "output": [
                "Does pretreatment with statins enhance myocardial protection during coronary revascularization?"
            ]
        },
        {
            "id": "task847-eff8c9af2d2a459a9fb0eb5edda4d778",
            "input": "Diabetes mellitus is a risk factor for death after coronary artery bypass grafting. Its relative risk may be related to the level of perioperative hyperglycemia. We hypothesized that strict glucose control with a continuous insulin infusion in the perioperative period would reduce hospital mortality.', 'All patients with diabetes undergoing coronary artery bypass grafting (n = 3554) were treated aggressively with either subcutaneous insulin (1987-1991) or with continuous insulin infusion (1992-2001) for hyperglycemia. Predicted and observed hospital mortalities were compared with both internal and external (Society of Thoracic Surgeons 1996) multivariable risk models.', 'Observed mortality with continuous insulin infusion (2.5%, n = 65/2612) was significantly lower than with subcutaneous insulin (5.3%, n = 50/942, P <.0001). Likewise, glucose control was significantly better with continuous insulin infusion (177 +/- 30 mg/dL vs 213 +/- 41 mg/dL, P <.0001). For internal comparison, multivariable analysis showed that continuous insulin infusion was independently protective against death (odds ratio 0.43, P =.001). Conversely, cardiogenic shock, renal failure, reoperation, nonelective operative status, older age, concomitant peripheral or cerebral vascular disease, decreasing ejection fraction, unstable angina, and history of atrial fibrillation increased the risk of death. For external comparison, observed mortality with continuous insulin infusion was significantly less than that predicted by the model (observed/expected ratio 0.63, P <.001). Multivariable analysis revealed that continuous insulin infusion added an independently protective effect against death (odds ratio 0.50, P =.005) to the constellation of risk factors in the Society of Thoracic Surgeons risk model.",
            "output": [
                "Does continuous insulin infusion reduce mortality in patients with diabetes undergoing coronary artery bypass grafting?"
            ]
        },
        {
            "id": "task847-328998908ddc45a5a6bc5120d8e12665",
            "input": "Although peritoneal washing cytology has been widely used in the field of gynecology, it has not been performed so frequently in patients with pancreatic cancer. Only a few papers have reported surgical implications of peritoneal washing cytology.', 'We reviewed results of peritoneal washing cytology performed immediately after laparotomy in 50 Japanese patients with pancreatic cancer. The 50 patients were divided into two groups according to the results of cytology. Clinicopathological findings were compared between these two groups.', 'Cytology of peritoneal washing was positive in 13 (26%) of the 50 patients. Nine of the 13 patients had no visible peritoneal dissemination. There were no significant differences regarding the age, tumor size and serum level of the carcinoembryonic antigen. Moderately to poorly differentiated adenocarcinoma and perineural invasion (ne3) and lymphatic permeation (ly3) of marked degree were more frequent in the positive group than in the negative group (p < 0.01). The survival curve of the 37 patients with negative cytology was significantly better than that of the 13 with positive cytology (p < 0.01). Four of 13 patients with positive cytology underwent a potentially curative resection but died within 12 months. Three of these four patients died of peritonitis carcinomatosa with massive malignant ascites and one died of local recurrence.",
            "output": [
                "Does positive washing cytology in patients with pancreatic cancer indicate a contraindication of pancreatectomy?"
            ]
        },
        {
            "id": "task847-98747f94b3b947928e1132b4c0a73e59",
            "input": "Survivin was aberrantly expressed in most cancer tissues, suggesting that survivin plays an important role in carcinogenesis. This study was designed to investigate the function and mechanism of survivin mutants in tumor cells.', 'The site-mutant and truncated survivin mutants were transfected into HeLa cells and selected using G418. Cell apoptosis was analyzed using flow cytometry. Protein level of cyclin D1 was detected by Western blot analysis.', 'Survivin mutant plasmid expressed in the HeLa cells successfully. The expressed protein could be detected using related antibody. Colony formation ability significantly decreased in the HeLa cells with survivin mutants compared with that in the parental HeLa cells. The HeLa cells transfected instantly with survivin mutants could undergo apoptosis automatically. Meanwhile, survivin mutants could cause an increase of multinuclear HeLa cells. The effect of survivin-N showed more effective than that of survivin T34A. Survivin-N and survivin T34A could influence the expression of cyclin D1 and reduced its protein levels of 68% and 12%, respectively.",
            "output": [
                "Do [ Survivin mutants reverse the malignancy of HeLa cells ]?"
            ]
        },
        {
            "id": "task847-b4644aca8b8645bc90a9f8cba071e074",
            "input": "To detect the presence of somatostatin (SOM) in normal aqueous humor and to characterize its immunosuppressive activity.', 'Fresh rabbit aqueous humor was assayed for SOM by competitive ELISA. Primed T cells stimulated through their T-cell receptor (TCR) were treated with SOM at concentrations that ranged the level of SOM found in normal aqueous humor. The T cells were assayed for proliferation, lymphokine production, and immunosuppressive activity.', 'Normal rabbit aqueous humor contained 196 +/- 45 pg/mL (10(-10) M) of SOM. At concentrations between 10 and 300 pg/mL, SOM suppressed IFN-gamma production by TCR-stimulated primed T cells in culture. Frozen and thawed aqueous humor depleted of SOM no longer suppressed IFN-gamma production by the TCR-stimulated primed T cells. SOM induced TGF-beta but not IL-4 production, nor did it suppress proliferation by TCR-stimulated primed T cells. The SOM-treated T cells functioned as regulatory T cells, and this regulatory activity was neutralized by anti-alpha-MSH antibodies. Furthermore, SOM induced alpha-MSH production by the TCR-stimulated primed T cells.",
            "output": [
                "Is somatostatin an immunosuppressive factor in aqueous humor?"
            ]
        },
        {
            "id": "task847-c0a5d57964a74df28e4845e9667fb870",
            "input": "Routine tuberculosis control services in Burundi.', 'To determine whether systematic restaining of sputum smears for acid-fast bacilli (AFB) prior to rechecking quality assessment is necessary.', 'Blinded rechecking of peripheral routine smears, including a second control of discordants, before and after restaining.', 'Without restaining, 10/825 (1.2%) negative, and 59/189 (31.2%) positive results were declared false. After restaining, there were 34 (4.1%) false negatives and 13 (6.9%) false positives, both highly significant changes. Before restaining, quantification of positive smears was usually considered too high, while after restaining 41 out of 42 positives were found to have too low readings.",
            "output": [
                "Is systematic restaining of sputum smears for quality control useful in Burundi?"
            ]
        },
        {
            "id": "task847-d3aebf1f29e647db94f3431c7817a624",
            "input": "Several studies on differences in infant outcome by socioeconomic position have been done, but these have usually been based on ad hoc data linkages. The aim of this paper was to investigate whether socioeconomic differences in perinatal health in Finland could be regularly monitored using routinely collected data from one single register.', 'Since October 1990, the Finnish Medical Birth Register (MBR) has included data on maternal occupation. A special computer program that converted the occupation name into an occupational code and into a socioeconomic position was prepared. Perinatal health was measured with five different indicators. The Finnish MBR data for years 1991 to 1999 (n=565 863 newborns) were used in the study. The study period was divided into three, three year periods to study time trends.', 'An occupational code was derived for 95% of women, but it was not possible to define a socioeconomic position for 22% of women, including, for example, students and housewives (the group \"Others\"). For the rest, the data showed socioeconomic differences in all perinatal health indicators. Maternal smoking explained up to half of the excess risk for adverse perinatal outcome in the lowest socioeconomic group. The socioeconomic differences narrowed during the 1990s: infant outcome improved in the lowest socioeconomic group, but remained at the same level or even deteriorated in other groups. When comparing the lowest group with the highest group, the odds ratios (OR) adjusted for maternal background characteristics at least halved for prematurity (from 1.32 (95% confidence intervals 1.24 to 1.43) in 1991-1993 to 1.16 (1.08 to 1.25) in 1997-1999), for low birth weight (from 1.49 (1.36 to 1.63) to 1.25 (1.17 to 1.40)), and for perinatal mortality (from 1.79 (1.44 to 2.21) to 1.33 (1.07 to 1.66)).",
            "output": [
                "Does register based monitoring show decreasing socioeconomic differences in Finnish perinatal health?"
            ]
        },
        {
            "id": "task847-a69ec24bae4946b789edef20c1dba0df",
            "input": "To assess the ability of an adult risk screening questionnaire (RSQ), previously shown to predict attendance at hospital emergency departments, to identify impaired quality of life in adult patients with asthma in general practice.', 'Baseline data from an RCT of asthma clinics in general practice, using the St. George Respiratory Questionnaire (SGRQ) to measure quality of life.', 'Twelve general practices in Adelaide, Australia.', 'A total of 184 adult asthmatics were recruited, with a mean (standard deviation) age of 50.3 years (16.6 years). Age, gender, weight, number of comorbidities, smoking status, FEV1 and percent predicted FEV1 (pre-and post-bronchodilator), peak flow (pre and post), and RSQ were independently related to SGRQ scores. After adjusting for potential confounders, an RSQ score predictive of hospital attendance was also associated with an average increase (worsening) in SGRQ total score of 11.9 (95% CI: 7.6, 16.3), an average increase in activity score of 9.0 (2.5, 15.5), symptom score of 14.8 (8.6, 21.0), and impact score of 13.1 (8.6, 17.6). These represent clinically significant differences.",
            "output": [
                "Does hospital attendance prediction tool also identify impaired quality of life in adults with asthma in general practice?"
            ]
        },
        {
            "id": "task847-2ffa4aa271e446cb84c4e1227b7491bd",
            "input": "The high affinity IgE receptor (FcepsilonRI) on mast cells and basophils is up-regulated by its own ligand IgE; however, the mechanism is unknown.', 'To study the IgE-mediated effect on FcepsilonRI on basophils by using the human basophilic cell line KU812.', 'Expression of cell surface FcepsilonRI was assessed by flow cytometry. Western blot technique was used to illustrate tyrosine-phosphorylation and the Ca2+ level in KU812 was measured by fluorescence of Fura-2. Soluble specimens of the alpha-chain from FcepsilonRI (FcepsilonRIalpha) were obtained by lysing 107 KU812 pr. mL. FcepsilonRIalpha was detected by a sandwich immunoradiometric assay employing the IgE-binding capacity of FcepsilonRIalpha in conjunction with a monoclonal antibody. Polyclonal rabbit anti-FcepsilonRIalpha was used for detection of FcepsilonRIalpha by Western blotting.', 'We found that monomeric IgE did not induce tyrosine-phosphorylation in KU812, which was the case when stimulating with IgE cross-linked by anti-IgE binding. Further, only cross-linking of IgE, but not monomeric IgE, increased the Ca2+ level. Using the immunoradiometric assay, we found a temperature dependent reduction in the amount of FcepsilonRIalpha. Samples incubated at 37 degrees C for 5 h displayed a 16-fold decrease in the FcepsilonRIalpha level compared with samples incubated at 4 degrees C. In the presence of IgE the reduction at 37 degrees C was only threefold.",
            "output": [
                "Does monomeric immunoglobulin E stabilize FcepsilonRIalpha from the human basophil cell line KU812 by protecting it from natural turnover?"
            ]
        },
        {
            "id": "task847-8f39a4966adc413188e6a0d07081f72f",
            "input": "Stroke, mainly attributable to atherothrombotic disease, represents a leading cause of disability and death in the Western world. Endothelial dysfunction, which is considered a key factor in atherogenesis, is associated with an increased risk of cardiovascular events. However, the magnitude of the association between coronary endothelial dysfunction (CED) and cerebrovascular events is unknown. This study was performed to investigate the association between CED and cerebrovascular events.', 'We studied 503 patients without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing by intracoronary acetylcholine infusion. Patients were divided according to the presence (n=305) or absence (n=198) of CED, and medical records were examined for the occurrence of ischemic or hemorrhagic stroke or transient ischemic attack either before (prevalent) or after (incident) coronary endothelial function testing. Among the study population, a total of 25 cerebrovascular events were documented, 22 in patients with CED (15 prevalent) and 3 in patients without (all prevalent) (P=0.008). Multivariable logistic regression, which included traditional cerebrovascular disease-related risk factors, identified the presence of CED as the single strongest factor associated with cerebrovascular events (OR, 4.32; 95% CI, 1.26 to 14.83). Kaplan-Meier analysis indicated that patients with CED had a significantly higher cumulative cerebrovascular event rate than those without (P=0.04).",
            "output": [
                "Is coronary endothelial dysfunction associated with an increased risk of cerebrovascular events?"
            ]
        },
        {
            "id": "task847-e87396b7203c429b80ea4dce73b738e3",
            "input": "Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly. Increased understanding of the pathogenesis is necessary. Amyloid-beta (Abeta), a major extracellular deposit in Alzheimer's disease plaques, has recently been found in drusen, the hallmark extracellular deposit in AMD. The goal of this study was to characterize the distribution and frequency of Abeta deposits in drusen from AMD and normal post mortem human retinas to gain additional insight about the potential role of Abeta in AMD patho genesis.\", 'Immunocytochemistry was performed with three Abeta antibodies on sections from 9 normal and 9 AMD (3 early, 3 geographic atrophy, 3 exudative AMD) retinas. Five sections from each eye were evaluated. Abeta positive deposits in drusen were identified using epifluorescence and confocal microscopy. Antibodies were pre-adsorbed with Abeta peptide to verify specificity. Some sections were stained with PAS-hematoxylin to aid in evaluation of morphology.', \"To test and optimize immunocytochemistry, Abeta was detected in amyloid plaques from Alzheimer's brains. Abeta label was blocked by pre-adsorption of antibody with Abeta peptide, verifying specificity. Four of the 9 AMD retinas and none of the 9 normal retinas had Abeta positive drusen. Two of the early AMD eyes had a few A[beta] positive drusen, each with a few Abeta-containing vesicles, and 2 of the geographic atrophy (GA) eyes had many Abeta positive drusen with many Abeta containing vesicles.",
            "output": [
                "Is amyloid-beta found in drusen from some age-related macular degeneration retinas , but not in drusen from normal retinas?"
            ]
        },
        {
            "id": "task847-b1189f2b1e8a44eeacc561acddecb4dd",
            "input": "To examine baseline hormonal concentrations and the pharmacokinetic response on day 0 and day 28 of 28 days of androstenedione supplementation.', 'Eight men (mean (SD) age 44.1 (3.0) years (range 40-48), weight 76.3 (9.4) kg, and percentage body fat 20.6 (6.7)) participated in a randomised, double blind, cross over, 2 x 28 day placebo controlled study. Subjects were tested on day 0 and 28 days after receiving 200 mg/day oral androstenedione and a placebo treatment with a 28 day washout period between treatments. Serum hormone concentrations were examined at baseline (time 0) and then at 30 minute intervals for 180 minutes to measure day 0 and day 28 pharmacokinetic responses. Analytes included androstenedione, total testosterone, dehydroepiandrosterone sulfate (DHEAS), oestradiol, and sex hormone binding globulin (SHBG). Lipid concentrations, weight, body composition, resting heart rate, and blood pressure were also measured.', \"Analysis of integrated area under the curve (AUC) and time 0 hormonal concentrations by repeated measures multivariate analysis of variance (p<0.05) and Fisher's post hoc analysis showed a significant increase in AUC for serum androstenedione at day 0 (108.3 (27.6) nmol/l) in the supplemented condition as compared with day 28 (43.4 (13.1) nmol/l) and placebo (2.1 (0.8) nmol/l) conditions. No other significant AUC changes were noted. After 28 days of supplementation, DHEAS levels were significantly elevated (p = 0.00002) at time 0 (12.9 (1.3) micro mol/l) compared with placebo (7.0 (0.8) micro mol/l) with a trend (p = 0.08) toward elevation of time 0 androstenedione concentrations (16.4 (7.0) nmol/l) compared with placebo (5.6 (0.4) nmol/l). No changes were found for lipids, resting heart rate, or blood pressure, weight, or percentage body fat.",
            "output": [
                "Does four weeks of androstenedione supplementation diminish the treatment response in middle aged men?"
            ]
        },
        {
            "id": "task847-00f3a02a447542cb8e43d4cf3dd19bbb",
            "input": "To assess the effects of soft contact lens base curve radius (BCR), sex, ethnicity, central corneal curvatures, and vertical palpebral aperture size (PAS) on the postlens tear thickness (PLTT).', 'The PLTT was measured using optical pachometry on 114 experienced lens wearers who were fitted with lathe-cut soft lenses (Alden 47, polymacon, 35.5% H2O, -2.00 diopter, and 14.0 mm). Each subject was randomly allocated to one lens group receiving a BCR of 7.9, 8.3, or 8.7 mm. Pachometry measurements were taken at 30 min after lens insertion. Vertical PAS and keratometry readings were measured for 94 of the 114 subjects.', 'The mean (95% confidence interval) PLTT was 15.7 microm (13.2-18.0 microm), 12.8 microm (10.9-14.7 microm), and 12.1 microm (10.2-14.0 microm) for the 7.9-mm, 8.3-mm, and 8.7-mm BCR groups, respectively. The differences in PLTT among the three BCR groups was significant (analysis of variance F-test; P=0.039). Post hoc testing using the Tukey honestly significant difference statistic showed that only the two extreme BCR groups (7.9 mm and 8.7 mm) were significantly different. Sex had no effect on the PLTT; however, the PLTT was significantly thinner for the Asian compared with non-Asian eyes (P=0.0001). The Asian PLTT did not vary with different soft lens BCRs. The non-Asian PLTT was thicker with lenses of the steep BCR compared with the flat BCR.",
            "output": [
                "Do the effects of ocular and lens parameters on the postlens tear thickness?"
            ]
        },
        {
            "id": "task847-07debe029c054c35a45f36e7da67095b",
            "input": "We investigated whether or not fibrinogen is related to the cardiovascular risk profile and complications in hypertensive subjects.', 'Plasma fibrinogen and laboratory tests including factor VII, homocysteine and microalbuminuria were evaluated in 127 consecutive hypertensive subjects stratified according to cardiovascular risk. Parameters were age, gender, smoking, cholesterol, diabetes, target organ damage: left ventricular hypertrophy (LVH), carotid atherosclerotic complications and retinical vessels.', 'Fibrinogen levels were significantly different between patients according to risk levels (low 290+/-73, n=20, high 342+/-94 mg/dl, n=39, very high risk 350+/-72, n=29, p=0.01), hypertension grade (II-III) and organ damage. Fibrinogen was significantly higher in patients with more severe carotid atherosclerotic lesions and vascular retinal lesions (grades II-III vs 0 and I). Also in patients, matched for age and sex, without and with carotid atherosclerotic lesions, fibrinogen was significantly higher in the latter group. No significant differences were found on the basis of IVS, creatinine and microalbuminuria. In hypertensive patients, fibrinogen directly correlated with age, by multiple linear regression. In hypertensive patients with diabetes, fibrinogen was significantly higher (466+/-176 mg/dL, n=14) than in those hypertensive without diabetes (333+/-87 mg/dL, n=113, p=0.001) and in all patients there was a a significant correlation (r=0.474, p<0.001) between blood glucose and fibrinogen.",
            "output": [
                "Are elevated plasma fibrinogen levels in patients with essential hypertension related to vascular complications?"
            ]
        },
        {
            "id": "task847-2d72546ffb2c48e6baf82c3152ca9422",
            "input": "To examine peripheral nerve stimulation (PNS) thresholds for normal human subjects in magnetic resonance imaging (MRI) gradient coils, and determine if observed thresholds could be predicted based on gross physiologic measurements.', 'PNS thresholds for 21 healthy normal subjects were measured using a whole-body gradient coil. Subjects were exposed to a trapezoidal echo-planar imaging (EPI) gradient waveform and the total change in gradient strength (DeltaG) required to cause PNS as a function of the duration of the gradient switching time (tau) were measured. Correlation coefficients and corresponding P values were calculated for the PNS threshold measurements against simple physiologic measurements taken of the subjects, including weight, height, girth, and average body fat percentage, in order to determine if there were any easily observable dependencies.', 'No convincing correlations between threshold parameters and gross physiologic measurements were observed.",
            "output": [
                "Do simple anatomical measurements correlate significantly to individual peripheral nerve stimulation thresholds as measured in MRI gradient coils?"
            ]
        },
        {
            "id": "task847-2ee898191cbb4833819e69f252f11866",
            "input": "Toenail onychomycosis is a common disease that can have serious adverse effects on the quality of life (QOL) of patients.', 'To evaluate the impact of itraconazole pulse therapy on the QOL of patients with toenail onychomycosis.', 'A total of 20 patients with disto-lateral subungual toenail onychomycosis were treated with itraconazole 200 mg twice daily for 1 week every 4 weeks for 12 weeks. The patients were asked to complete a QOL questionnaire before treatment and on the last follow-up visit (week 48). A score of 0-4 was given according to the five possible responses to each question and these were summed to give the final score of the patient. The mean of the final scores of the patients before and after treatment were compared using the Wilcoxon matched-pairs test.', 'At 48 weeks after commencing treatment, 14 patients (70%) responded to treatment (nine patients were cured with almost totally clear toenails and five patients improved), and 16 patients (80%) were mycologically cured (negative KOH smear and culture). The mean of the QOL scores of the patients before treatment was 18.0+/-7.8, which reduced to 13.1+/-11.3 after treatment (two-tailed, p=0.009).",
            "output": [
                "Does itraconazole pulse therapy improve the quality of life of patients with toenail onychomycosis?"
            ]
        },
        {
            "id": "task847-f4653175728d445da25bb2850794d5e4",
            "input": "Amifostine is an organic thiophosphate that may selectively protect normal tissues from the toxicities of chemotherapy. The combination of fludarabine and cyclophosphamide (FC) is highly active in patients with chronic lymphocytic leukemia (CLL). Infection is a serious toxicity of the FC regimen.', 'Amifostine was added to the FC regimen in a phase II study of 46 patients with CLL. Patients received FCA (fludarabine 30 mg/m(2) i.v. daily for 3 days, cyclophosphamide 300 mg/m(2) i.v. daily for 3 days, and amifostine 500 mg i.v. over 15 min daily for 3 days starting 30 min before cyclophosphamide) at intervals of 4-6 weeks for a maximum of six courses.', 'Patients receiving FCA had equivalent rates of sepsis, early death, objective response and survival to those observed in a prior series of 78 patients treated with FC. Amifostine-associated toxicities included nausea, vomiting, and hypotension.",
            "output": [
                "Does amifostine reduce the toxicity of the fludarabine and cyclophosphamide regimen in patients with chronic lymphocytic leukemia?"
            ]
        },
        {
            "id": "task847-4a5a43bd961c4f368797462f28fde6f3",
            "input": "Most solid human tumors exist in an acidic microenvironment, due in part to inefficient vasculature and a higher intrinsic rate of glycolysis. This leads to a tumor-selective pH gradient, which can be exploited therapeutically with antitumor agents such as the camptothecins (CPTs). Previous work in this laboratory has shown that camptothecin activity is enhanced 40- to 60-fold in monolayer cell culture by reducing the extracellular pH to 6.8. Three-dimensional histoculture has been shown to be a technique that allows human tumor tissue to grow in an in vivo-like way with maintenance of tissue histology and function and drug sensitivity for long periods of time.', 'In the current study, we utilized these features of histoculture to study new analogues of camptothecin that have superior pharmacological properties.', 'We evaluated six CPT analogues in histocultures of human brain, neuroblastoma, breast, colon, and prostate tumors. Fragments were exposed to 10,11-methylenedioxy-CPT (MDC), 7-chloromethyl-MDC, SN-38, topotecan (TPT), 9-amino-CPT, 10-amino-CPT, paclitaxel, 5-fluorouracil, 4-hydroperoxycyclophosphamide and doxorubicin, and antitumor activity was assessed. For in vivo tumor outgrowth studies, fragments were treated in parallel, implanted into nude mice, and monitored for development of tumors. RESULTS. Against 15 of 16 tumor xenografts and all primary tumor samples tested, all compounds were cytotoxic at pH 7.4 (IC(50) range 13-921 microM). MDC, SN-38, TPT, and 9-amino-CPT achieved an average 5-fold increase in activity (range 3-14) at pH 6.8, while 7-chloromethyl-MDC was enhanced 8-fold (range 6-14). The most potentiated analogue was 10-amino-CPT at 27-fold (range 17-49). In contrast, the other agents were active against one or more tumor types but were not enhanced by acidic pH. Importantly, the toxicity of MDC in histoculture of D54 glioma xenografts strongly correlated with the outgrowth of treated fragments subsequently implanted in vivo.",
            "output": [
                "Is the activity of camptothecin analogues enhanced in histocultures of human tumors and human tumor xenografts by modulation of extracellular pH?"
            ]
        },
        {
            "id": "task847-8f90abddf870456fb1fd8ab903f80ede",
            "input": "There are few data concerning prognostic markers of acute myocarditis. The purpose of this study was to assess the prognostic value of initial measurements of creatine kinase (CK), cardiac troponin I (cTnI) and myoglobin as regards late recovery of the left ventricular ejection fraction on follow-up.', 'A total of 22 patients (53+/-15 years old, 11 female) with acute myocarditis were followed up in a prospective observational study. Of these, 11 (50%) showed a history of acute infection prior to hospitalisation and seven (32%) had pericardial effusion. The median ejection fraction during the acute phase was 47+/-17%; after a mean follow-up of 119+/-163 days it improved to 60+/-9% (P<0.001). Considering maximal CK-rise values of 641+/-961 U/l (P=0.38), cTnI-rise values of 3.7+/-8.6 microg/l (P=0.16) and myoglobin values of 7.4+/-12 nmol/l (P=0.69), there was no correlation between initial cardiac enzyme levels and the initial and late left ventricular ejection fraction.",
            "output": [
                "Is long-term outcome of acute myocarditis independent of cardiac enzyme release?"
            ]
        },
        {
            "id": "task847-dcc28351d8fe447a93a0b31eb336a7b3",
            "input": "Previous studies have observed that activation of cyclooxygenase-2 contributes to generation of superoxide anion after fluid percussion brain injury (FPI). This study was designed to characterize the effects of FPI on the vascular activity of two activators of a pertussis toxin-sensitive G protein, mastoparan and mastoparan-7, and the role of cyclooxygenase-2-dependent superoxide anion generation in such effects as a function of age.', 'Lateral FPI was induced in anesthetized newborn (1-5-day-old) and juvenile (3-4-week-old) pigs equipped with a closed cranial window.', 'Mastoparan (10(-8), 10(-6) M) elicited pial artery dilation that was blunted more in newborn versus juvenile pigs (9 +/- 1 and 16 +/- 1 vs. 3 +/- 1 and 5 +/- 1%, newborn; 9 +/- 1 and 15 +/- 1 vs. 6 +/- 1 and 9 +/- 1%, juveniles). Similar results were observed for mastoparan-7 but the inactive analog mastoparan-17 had no effect on pial artery diameter. Indomethacin (a cyclooxygenase-1 and cyclooxygenase-2 inhibitor), NS398 (a cyclooxygenase-2 inhibitor), and polyethylene glycol superoxide dismutase and catalase (free radical scavengers) partially restored impaired mastoparan dilation after FPI in the newborn in a roughly equivalent manner but not in the juvenile (3 +/- 1 and 5 +/- 1 vs. 8 +/- 1 and 13 +/- 1% newborn, 6 +/- 1 and 9 +/- 1 vs. 7 +/- 1 and 10 +/- 1% juvenile for NS398 pretreatment).",
            "output": [
                "Does cyclooxygenase-2-dependent superoxide generation contribute to age-dependent impairment of G protein-mediated cerebrovasodilation?"
            ]
        },
        {
            "id": "task847-e50e59a2368e470085a12259439b0b4b",
            "input": "Hyperglycemia generates reactive oxygen species and prevents isoflurane-induced preconditioning. The authors tested the hypothesis that scavenging reactive oxygen species with N-acetylcysteine will restore protection against myocardial infarction produced by isoflurane in vivo.', 'Barbiturate-anesthetized dogs (n = 45) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size and coronary collateral blood flow were measured with triphenyltetrazolium staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of 0.9% saline or 15% dextrose in water to increase blood glucose concentrations to 600 mg/dl (hyperglycemia) in the absence or presence of isoflurane (1.0 minimum alveolar concentration) with or without pretreatment with N-acetylcysteine (150 mg/kg i.v.) in six experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion.', 'Myocardial infarct size was 27 +/- 2% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%; n = 7). Hyperglycemia alone did not alter infarct size (29 +/- 3%; n = 7) but abolished the protective effect of isoflurane (25 +/- 2%; n = 8). N-Acetylcysteine alone did not affect infarct size (28 +/- 2%; n = 8) but restored isoflurane-induced cardioprotection during hyperglycemia (10 +/- 1%; n = 7).",
            "output": [
                "Does n-acetylcysteine restore isoflurane-induced preconditioning against myocardial infarction during hyperglycemia?"
            ]
        },
        {
            "id": "task847-8c918cbc12674b3abbcf6a1eb30fca36",
            "input": "General anesthesia may delay the onset of movement in response to noxious stimulation. The authors hypothesized that the production of immobility could involve depression of time-related processes involved in the generation of movement.', 'The delays (latencies) between onset of tail clamp (n = 16) or 50-Hz continuous electrical stimulation (n = 8) and movement were measured in rats equilibrated at 0.1-0.2% increasing steps of isoflurane. In other rats (n = 8), the isoflurane concentrations just permitting and preventing movement (crossover concentrations) in response to trains of 0.5-ms 50-V square-wave pulses of interstimulus intervals of 10, 3, 1, 0.3, or 0.1 s during the step increases were measured. These measures were again made during administration of intravenous MK801, an N-methyl-D-aspartate receptor antagonist that can block temporal summation (n = 6). Temporal summation refers to the cumulative effect of repeated stimuli. Crossover concentrations to 10- and 0.1-s interstimulus interval pulses ranging in voltage from 0.25-50 V were also measured (n = 4).', 'The increase in concentrations from 0.6 to nearly 1.0 minimum alveolar concentration progressively increased latency from less than 1 s to 58 s. Shortening the interstimulus interval (50 V) pulses from 10 to 0.1 s progressively increased crossover concentrations from 0.6 to 1.0 minimum alveolar concentration. In contrast, during MK801 administration shortening interstimulus intervals did not change crossover concentrations, producing a flat response to change in the interstimulus interval. Increasing the voltage of interstimulus interval pulses increased the crossover concentrations but did not change the response to change in interstimulus intervals for pulses greater than 1 V.",
            "output": [
                "Does temporal summation govern part of the minimum alveolar concentration of isoflurane anesthesia?"
            ]
        },
        {
            "id": "task847-a96b9fe6e54b42fbb76f72331691da68",
            "input": "The transcription factor Pdx1 is required for the development and differentiation of all pancreatic cells. Beta-cell specific inactivation of Pdx1 in developing or adult mice leads to an increase in glucagon-expressing cells, suggesting that absence of Pdx1could favour glucagon gene expression by a default mechanism.', 'We investigated the inhibitory role of Pdx1 on glucagon gene expression in vitro. The glucagonoma cell line InR1G9 was transduced with a Pdx1-encoding lentiviral vector and insulin and glucagon mRNA levels were analysed by northern blot and real-time PCR. To understand the mechanism by which Pdx1 inhibits glucagon gene expression, we studied its effect on glucagon promoter activity in non-islet cells using transient transfections and gel-shift analysis.', 'In glucagonoma cells transduced with a Pdx1-encoding lentiviral vector, insulin gene expression was induced while glucagon mRNA levels were reduced by 50 to 60%. In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the alpha-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3.",
            "output": [
                "Does ectopic expression of the beta-cell specific transcription factor Pdx1 inhibit glucagon gene transcription?"
            ]
        },
        {
            "id": "task847-eaffed9ab3cd4920966bc7d536abbb35",
            "input": "Caffeine is frequently used during pregnancy and associated with teratogenic effects, such as low birth weight, hearth and digital defects, cleft palate and abortion with fetal loss. This study investigated histopathologically the effects of caffeine on neonatal rat cornea.', 'Fifty pregnant Wistar-Albino rats (dams) were randomly divided into five groups, one control and four experimental. Between day 9 and 21 of gestation, group 1 dams (control, n=10) were exposed to intraperitoneal (i.p.) SF daily until delivery. Group 2 (n=10), group 3 (n=10) and group 4 (n=10) dams were treated with i.p. caffeine at doses of 25, 50 and 100 mg/kg/d, respectively, for the same period. Group 5 dams were given caffeine in distilled water in a gavage at a dose of 50 mg/kg/d during the same period. After normal delivery, the litters were killed at postnatal day 1 or 30 and the eyes were enucleated for corneal histopathologic investigation.', 'Control and group 1 eyes had normal corneal epithelium, regular stromal fibers, descement membrane and monolayer inner corneal endothelium. The remaining experimental litters demonstrated changes, such as vacuolated endothelial cells with proliferation, hyperchromasia, polymorphism, endothelial cell agenesis, increased stromal mitotic activity and focal increase in corneal thickness with widely separated corneal lamellae in the injured area. These changes occurred most often in the litters treated with high doses of caffeine.",
            "output": [
                "Does high dose of caffeine administered to pregnant rats cause histopathological changes in the cornea of newborn pups?"
            ]
        },
        {
            "id": "task847-1315d459dea84674ac9e40add8976ecd",
            "input": "This study was designed to investigate the effects of simvastatin in a rat model of acute myocardial infarction.', 'Male Wistar rats were anesthetized (thiopentone sodium 120 mg/kg). After a thoracotomy, the left-anterior-descending coronary artery (LAD) was occluded (for 25 min) and reperfused (for 120 min). Area at risk (AR) was determined with Evans Blue dye and infarct size after staining of the area at risk with nitroblue tetrazolium.', 'In rats, which received the vehicle for simvastatin (10% DMSO, 1 ml/kg i.v. at 1 h prior to the occlusion of the LAD), occlusion of the LAD for 25 min followed by reperfusion for 2 hours resulted in an infarct size of 54 +/- 4% (n=7) of the AR. When compared with vehicle, administration of simvastatin (1 mg/kg i.v. bolus administration at 1 h prior to the onset of myocardial ischemia) caused a significant reduction in myocardial infarct size of 39%. LAD-occlusion and reperfusion caused a progressive fall in mean arterial blood pressure (when compared with sham-operated animals). Simvastatin had no significant effect on blood pressure.",
            "output": [
                "Does simvastatin reduce infarct size in a model of acute myocardial ischemia and reperfusion in the rat?"
            ]
        },
        {
            "id": "task847-0bab941feb0648a68aca6e9760fc30f5",
            "input": "To investigate the effect of low doses of 60 kVp X-rays on in vitro transformation frequency.', 'HeLa x skin fibroblast human hybrid cells were used to assay transformation from the non-tumorigenic to the tumorigenic phenotype. Subconfluent cultures of cells were exposed to a range of doses of 60 kVp X-rays and seeded for assay of transformation after 24 h post-irradiation holding. Experiments were repeated at least three times and the data pooled for analysis. Transformation frequencies were compared with those of sham-irradiated controls.', 'At doses < 1 cGy, the observed transformation frequencies were significantly less than those seen in unirradiated cells.",
            "output": [
                "Do low doses of diagnostic energy X-rays protect against neoplastic transformation in vitro?"
            ]
        },
        {
            "id": "task847-da76a7297cc34fd08108f84579aac680",
            "input": "Current conceptualizations of drug reinforcement assume that drug-taking behavior is a consequence of the contingent, temporal relationship between the behavior and drug reward. However, stimulant drugs also potentiate the rewarding effects of other reinforcers when administered noncontingently.', 'These studies were designed to determine whether noncontingent nicotine enhances the reinforcing properties of a nonpharmacological reinforcer and whether this direct effect facilitates operant behavior within the context of a nicotine self-administration procedure.', 'Rats self-administered nicotine or food, or received noncontingent nicotine, saline, or food either with or without a response-contingent, unconditioned reinforcing visual stimulus (VS).', 'Noncontingent nicotine, whether delivered as discrete injections based on a pattern of self-administered nicotine or as a continuous infusion, increased response rates maintained by the VS. There were no significant differences in responding by animals that received contingent compared with noncontingent nicotine when a VS was available. This increase was not observed in the absence of the VS or as a consequence of noncontingent food delivery. Operant behavior was equally attenuated and reinstated by the removal and subsequent replacement of contingent and noncontingent nicotine. Nicotine supported self-administration in the absence of response-contingent, nicotine-paired stimuli; however, response rates were drastically reduced compared with nicotine self-administration with the VS.",
            "output": [
                "Is operant responding for a visual reinforcer in rats enhanced by noncontingent nicotine : implications for nicotine self-administration and reinforcement?"
            ]
        },
        {
            "id": "task847-f822a75c47ae4104946ea3b3e582ebbf",
            "input": "To study the influence of the severity of depression on the eating disorder's inventory (EDI) scores in anorexia nervosa (AN) patients.\", \"We compared by variance analysis the EDI scores from three groups of AN patients: 55 patients having a major depression (as assessed by a Beck's depression inventory (BDI) >/= 16); 77 patients having a less severe depression (BDI < 16); 32 patients with mild or non-existent depression (BDI </= 7) and the EDI scores from a control group of 29 French healthy young women.\", 'Higher EDI scores were elicited in the more severely depressed AN patients than in the less- or non-depressed AN patients (P < 0.01). In non-depressed AN patients, none of the scores was different from those of the control group. This was particularly true for the scores \"Slimness wish\", \"bulimia\", \"body image dissatisfaction\", \"perfectionism\" and \"fear of maturity\". The non-depressed restrictive AN patients had no score which differ from healthy controls.",
            "output": [
                "Does depression influence the EDI scores in anorexia nervosa patients?"
            ]
        },
        {
            "id": "task847-47c8c9cf7d53442a9adbe7a1f8d3ca28",
            "input": "Endothelial cells (EC) shed endothelial microparticles (EMP) in activation and apoptosis.', 'We compared the antigenic expression of EMP species released during activation as compared to apoptosis, in three cell lines.', 'EC from renal and brain microvascular (MiVEC) and coronary macrovascular (MaVEC) origin were incubated with TNF-alpha to induce activation, or deprived of growth factors to induce apoptosis. Antigens expressed on EMP and EC were assayed flow cytometrically and included constitutive markers (CD31, CD51/61, CD105), inducible markers (CD54, CD62E and CD106), and annexin V binding.', 'It was found that in apoptosis, constitutive markers in EMP were markedly increased (CD31>CD105), with a concomitant decrease in expression in EC. Annexin V EC surface binding and annexin V+ EMP were more sharply increased in apoptosis than in activation. In contrast, in activation, inducible markers in EMP were markedly increased in both EMP and EC (CD62E>CD54>CD106). Coronary MaVEC released significantly less EMP than MiVEC.",
            "output": [
                "Do endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis?"
            ]
        },
        {
            "id": "task847-9bcf3cf7b76d47d3a734ea593ac1f015",
            "input": "Dendritic cells (DC) are critical for induction of antitumor immunity. Recent studies suggest that tumors may avoid immune destruction by inhibiting DC function. The authors investigated the effect of neuroblastoma (NB) on surface antigen expression and T cell activation by DCs.', 'DCs were generated in the presence of granulocyte and macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) from peripheral blood of healthy donors. On day 6 of culture, DCs were exposed to human NB cells and were analyzed by flow cytometry.', 'The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) failed to upregulate the expression of HLA-DR and costimulatory molecule CD86 by DCs that were cultured with NB. Conversely, upregulation was preserved when DCs were cultured in the absence of NB. Exposure to NB also led to apoptosis of DCs as shown by 2-fold increase in surface phosphatidylserine. It appears that direct contact was required to inhibit DC maturation, because DCs separated from NB cells using a transwell insert did not suppress surface antigen expression. Finally, DCs exposed to NB inhibited the proliferation of allogeneic T cells in mixed lymphocyte reactions.",
            "output": [
                "Do neuroblastoma cells inhibit the immunostimulatory function of dendritic cells?"
            ]
        },
        {
            "id": "task847-a6a95afc03bc4fbf962e2ce60a4c973e",
            "input": "The authors previously described the complete regression of established neuroblastoma (NB) by the adoptive transfer of syngeneic interleukin-12 transduced dendritic cells (DC) from naive mice. However, some malignancies, like NB, abrogate DC immunostimulation. The authors hypothesize that IL-12 transduction of DC from NB-bearing mice will have the same antitumor properties.', 'A/J mice (n = 32) with established NB received peritumoral injection of 1 x 10(6) DC (DC, IL-12 DC, day 7 IL-12 DC or day 14 IL-12 DC) on day 7. Tumor growth, phenotype, and ability to induce NK and T cell activity were measured.', 'Vaccination with naive admIL-12 DC resulted in 100% tumor regression and prolonged survival. Transduced DC induced only partial responses in 75% (day 7) and 25% (day 14) of animals. No differences in phenotype or effector cell activation were noted between admIL-12DC in tumor-bearing or naive mice.",
            "output": [
                "Does advanced neuroblastoma impair dendritic cell function in adoptive immunotherapy?"
            ]
        },
        {
            "id": "task847-d2daddae2ba04c8f8f15068230d223f1",
            "input": "After massive small bowel resection (SBR), enterocyte apoptosis is elevated and inversely correlates with epidermal growth factor receptor (EGFR) signaling. The purpose of the current study was to determine whether EGFR manipulation affects the expression of specific bcl-2 family members.', 'A 50% proximal SBR or sham operation was performed in 3 groups of mice control, after exogenous EGF, or mutant mice with defective EGFR signaling (waved-2). Apoptotic index (no. of apoptotic bodies per crypt), and bax (pro-apoptosis) and bcl-w (anti-apoptosis) protein expression was measured in the remnant ileum after 12, 24, and 72 hours.', 'Waved-2 mice with defective EGFR showed the greatest increase in apoptosis and altered the ratio of bax to bcl-w in favor of apoptosis after SBR. Conversely, EGF prevented the expected increase in apoptosis after SBR by shifting the ratio of bax to bcl-w in favor of cell survival.",
            "output": [
                "Does eGF receptor signaling affect bcl-2 family gene expression and apoptosis after massive small bowel resection?"
            ]
        },
        {
            "id": "task847-f90dc2d818134687a254c9362eef9e10",
            "input": "Expression of vascular endothelial growth factor (VEGF)-D by tumors is associated with metastasis to lymph nodes in mice. However, there are few reports concerning the clinical significance of VEGF-D protein in human carcinoma.', 'After confirming production of VEGF-D by eight colorectal carcinoma cell lines, we investigated relationships between the expression of VEGF-D protein, lymph node metastasis and postoperative survival in 83 colorectal carcinoma patients. mRNA levels in cell lines were evaluated using the real-time reverse transcriptase-polymerase chain reaction, and protein was detected by Western blotting in cell lines and by immunohistochemistry in resected tissues using an antibody recognizing the processed form of the molecule.', 'Immunohistochemistry showed VEGF-D-positive staining in 26 of the 83 carcinomas (31%). There was a significant relationship between the presence of VEGF-D protein and the incidence of lymph node metastasis (p < 0.01). Multivariate logistic regression analysis revealed that VEGF-D protein expression was an independent factor affecting lymph node metastasis (p < 0.01). Nonetheless, the presence or absence of VEGF-D protein had no significant impact on the survival of the patients (p = 0.15).",
            "output": [
                "Is expression of vascular endothelial growth factor D associated with lymph node metastasis in human colorectal carcinoma?"
            ]
        },
        {
            "id": "task847-9240be3330f84cdd93c49d340c145e63",
            "input": "A reduced capacity of antigen presenting cells (APC) to provide pro-T helper 1 (Th1) signals, such as IL-12, to T cells during early life may be implicated in the development of T helper 2 (Th2)-mediated allergic disease. In this study we examined the relationships between the capacity for IL-12 responses in the neonatal period and atopic risk (family allergy), in vitro T cell responses to allergens, and the subsequent development of allergic disease at 6 years.', 'The capacity of circulating neonatal (and maternal) APC to produce IL-12 p70 in response to LPS (and IFN-gamma) stimulation was assessed in a group of 60 children with previously well-characterized immune responses to allergens and atopic outcomes. The IL-12 responses were compared with allergen-induced lymphoproliferation (to house dust mite (HDM) ovalbumin (OVA), cat and beta-lactoglobulin (BLG)) and IL-13 and IFN-gamma cytokine responses (to OVA, HDM and phytohaemaglutinin (PHA)) in the neonatal and postnatal periods. IL-12 responses were also compared according to atopic risk and atopic outcomes (doctor-diagnosed asthma, eczema, food allergies and sensitization as evidenced by skin prick testing) at 6 years clinical follow-up.', 'Maternal peripheral blood mononuclear cells (PBMC) synthesized significantly greater amounts of IL-12 than neonatal PBMC, though within maternal-infant pairs IL-12 responses were significantly correlated (r = 0.4, P = 0.019). Moreover, neonatal IL-12 responses were positively correlated with neonatal allergen proliferation for HDM (r = 0.6, P < 0.0001), OVA (r = 0.55, P < 0.0001), cat (r = 0.5, P = 0.003) and BLG (r = 0.55, P = 0.001), but negatively correlated with neonatal IL-13 responses to both allergens tested (HDM: r = - 0.4, P = 0.03 and OVA: r = - 0.5, P = 0.001). Both neonatal and maternal IL-12 responses were positively correlated with postnatal IFN-gamma responses to HDM at 12, 18 and 24 months of age (responses after age of 2 years were not assessed). There was no relationship between atopic risk and IL-12 capacity in the neonatal period, but there was a (non-significant) trend for neonatal IL-12 responses to be lower in the high-risk children who developed clinical allergy at 6 years (compared with the low risk group) although the number in this analysis was small.",
            "output": [
                "Is neonatal interleukin-12 capacity associated with variations in allergen-specific immune responses in the neonatal and postnatal periods?"
            ]
        },
        {
            "id": "task847-d4aaec4c7bcc4a7987a9d12ef9a98804",
            "input": "To demonstrate the effect in vivo of the myocilin gene mutation Thr377Met on outflow facility of aqueous humor, as measured by tonography.', 'Forty-two members of a pedigree known to carry the Thr377Met mutation were examined for glaucoma, evaluated with tonography, and screened for myocilin mutations. Tonography was used to calculate the coefficient of aqueous outflow facility (C), as well as the ratio of the resting intraocular pressure to C (P(0)/C). Subjects were reexamined for glaucoma 5 years after tonography.', \"Seven subjects were excluded because of previous treatment known to alter facility of aqueous outflow. The mean outflow facility of the eyes of the 12 subjects carrying the Thr377Met mutation was significantly reduced compared with the 23 non-carriers' eyes using both C (P<0.001) and P(0)/C (P<0.001). Reduced outflow facility was also demonstrated in those mutation carriers who were not yet expressing clinical signs of glaucoma or ocular hypertension when measured using C (P = 0.015) and P(0)/C (P = 0.001). After 5 years, progression towards glaucoma had occurred in 5 of the myocilin mutation-carriers, 2 of whom showed bilateral progression; 3 carriers remained completely normal. Four subjects had bilateral glaucoma at the outset and remained unchanged. The carriers' eyes that progressed towards glaucoma had reduced outflow facility compared with those that remained normal, although the difference was not statistically significant.",
            "output": [
                "Does tonography demonstrate reduced facility of outflow of aqueous humor in myocilin mutation carriers?"
            ]
        },
        {
            "id": "task847-f6fb7b34e860426b9afdbe2d7d05d85b",
            "input": "Some patients become full donor chimeras (DC) early after stem-cell transplantation (SCT), while others remain mixed chimeras for a longer time. Little is known about the mechanism behind these phenomena.', 'Serum cytokine levels during conditioning and during the first month after SCT were analysed in 30 patients. Of the 21 patients who became full T-cell DC from the first analysed sample, 12 developed grade II-IV acute graft-vs.-host disease (GVHD) and the other nine, mild or no acute GVHD. Another nine patients were T-cell mixed chimeras (MC). All MC patients had no or mild acute GVHD.', 'During the pretransplant conditioning, DC patients had higher levels of tumour necrosis factor (TNF)-alpha and lower levels of transforming growth factor (TGF)-beta and interleukin (IL)-10, compared with MC patients. During the first week after SCT, lower levels of TGF-beta and IL-10 and higher levels of soluble Fas (sFas) were found in DC patients compared with MC patients. During the second and third weeks after SCT, increased levels of TNF-alpha, interferon (IFN)-gamma and sFas were found among DC patients compared with MC patients. Patients who developed moderate-to-severe acute GVHD had higher levels of TNF-alpha, IFN-gamma, IL-10 and sFas at 2 weeks post-SCT than in those with less GVHD. Patients homozygous for the TNFd microsatellite alleles 3 or 4 had significantly higher TNF-alpha levels during conditioning and more often developed acute GVHD grades II-IV.",
            "output": [
                "Do serum levels of cytokines correlate to donor chimerism and acute graft-vs.-host disease after haematopoietic stem cell transplantation?"
            ]
        },
        {
            "id": "task847-36dbbf7dd2964564bd2f1408f3f4bcca",
            "input": "Monitoring of respiratory mechanics during ventilator treatment in paediatric intensive care is currently based on pressure and flow measurements in the ventilator or at the Y-piece. The characteristics of the tracheal tube will modify the pressures affecting the airways and alveoli in an unpredictable manner. The dynostatic algorithm (DSA), based on a one-compartment lung model, calculates the alveolar pressure during on-going ventilation. The DSA is based on accurate measurement of tracheal pressure. The purpose of this study was to test the validity of the DSA in a paediatric lung model and to apply the concept in an observational clinical study in children.', 'We validated the DSA in a paediatric lung model with linear, nonlinear pressure flow and frequency-dependent characteristics by comparing calculated dynostatic (alveolar) pressures with directly measured alveolar pressures in the model and proximal plateau pressure with maximum alveolar pressure. Sixty combinations of ventilation modes, positive end expiratory pressures, inspiratory : expiratory ratios, volumes and frequencies were studied. A 0.25-mm fibreoptic pressure transducer in the tube lumen was used in combination with volume and flow from ventilator signals. Clinical measurements were performed in eight patients during anaesthesia and postoperative ventilator treatment.', 'In the lung model we found a correlation coefficient between calculated and measured alveolar pressure of 0.93-0.99 with root mean square median values of 1 cm H2O. Distal plateau pressure agreed well with maximum alveolar pressure. In the clinical situation, the algorithm provided a breath-by-breath display of the volume-dependent lung compliance and the temporal course of alveolar pressure during uninterrupted ventilation.",
            "output": [
                "Does the dynostatic algorithm accurately calculate alveolar pressure on-line during ventilator treatment in children?"
            ]
        },
        {
            "id": "task847-d64959a356e4416baf1bf90e66e339ad",
            "input": "Heat shock protein (HSP)70-2 is an important immunomodulatory protein induced in response to inflammatory stimuli. We assessed whether HSP70-2+1267 genotype influenced the risk of septic shock in a prospective cohort study of community-acquired pneumonia and whether HSP70-2+1267 genotype is a better predictor of septic shock than the genotype at lymphotoxin-alpha +250.', 'Prospective cohort study.', 'A large, nonprofit, private hospital system in Memphis, TN.', 'Adults admitted with community-acquired pneumonia between 1998 and 2001. Septic shock was defined according to consensus criteria (American College of Chest Physicians/Society of Critical Care Medicine, 1992).', 'Blood sampling.', 'A total of 343 subjects were enrolled; 30 had septic shock. HSP70-2+1267 and lymphotoxin-alpha +250 genotype was determined using polymerase chain reaction and restriction enzyme digestion. HSP70-2+1267 AA genotype was the strongest predictor of septic shock (p =.0005; relative risk, 3.5). Lymphotoxin-alpha +250 AA genotype was also associated with an increased risk of septic shock (p =.002; relative risk, 2.7). Logistic regression analysis found only age (p =.04) and HSP70-2+1267 genotype (p =.006) were predictors of septic shock. The greatest risk of septic shock was associated with carriage of the HSP70-2+1267 A/lymphotoxin-alpha +250 A haplotype (p <.0001).",
            "output": [
                "Do heat shock protein 70-2+1267 AA homozygotes have an increased risk of septic shock in adults with community-acquired pneumonia?"
            ]
        },
        {
            "id": "task847-01403dd9f28747c88d9450fab5ffd88c",
            "input": "The purpose of this study was to investigate whether midazolam exhibits characteristics of a highly permeable P-glycoprotein (P-gp) substrate and to evaluate the potential influence of P-gp inhibition on 1-OH midazolam formation during midazolam transport.', 'P-gp interaction was investigated by P-gp ATPase assay, efflux inhibition studies, and transport studies of midazolam across MDR1-MDCK and 1-alpha,25-dihydroxy vitamin D3-induced Caco-2 monolayers with and without the P-gp inhibitor GF120918.', \"Midazolam was highly permeable and transport appeared essentially unpolarized. In MDR1-MDCK, the basolateral-to-apical (B-to-A) permeability was slightly higher (16%) than apical-to-basolateral (A-to-B) permeability (p = 0.04); GF120918 increased A-to-B permeability by 27% (p = 0.01), and increased cellular midazolam accumulation during A-to-B transport by 45% (p = 0.01). Midazolam (200 microM) decreased rhodamine123 and vinblastine B/A ratios 3-fold (p < 0.006), while increasing their cellular accumulation (p < 0.003). P-gp ATPase activation by midazolam was dose-dependent and saturable [Km = 11.5(+/- 4.0) microM; Vmax = 41.1(+/- 7.4) nmol/mg/min]. P-gp inhibition increased 1-OH midazolam formation in A-to-B studies 1.3-fold when midazolam donor > or = 10 microM (p < 0.03). In B-to-A studies, P-gp inhibition did not significantly increase metabolite formation (p = 0.06). Midazolam's extraction ratio was not influenced by P-gp (p = 0.2).",
            "output": [
                "Does midazolam exhibit characteristics of a highly permeable P-glycoprotein substrate?"
            ]
        },
        {
            "id": "task847-11e65672b95045cd881737478e166c02",
            "input": "Studies associate atheroemboli with neurologic complications following cardiac surgery. The International Council of Emboli Management (ICEM) has demonstrated debris is captured when intraaortic filtration is employed during cardiac surgery. Particulate debris has been extracted from over 98% of ICEM patients and fibrous atheroma from 73%. Anastomotic device use may reduce aortic manipulation, minimizing debris. This study compares particulate capture among three patient groups: Cohort 1 (n = 745) patients receiving on-pump CABG-only procedures; Cohort 2 (n = 24) patients receiving off-pump CABG-only procedures with conventional anastomoses; Cohort 3 (n = 10) patients receiving off-pump CABG-only procedures with automatic proximal anastomoses.', 'The intraaortic filter was placed distal to anastomoses, and proximal to the innominate artery. Upon removal, filters were fixed in formalin and shipped to a core lab (Stanford, CA). Demographic, procedural, and outcomes data were collected in the ICEM Registry.', 'Of the 745 patients receiving stopped-heart CABG, complete data on preoperative risk factors was reported for 673 patients. At least 19 patients reported complete data in Cohort 2, and 10 reported in Cohort 3. One adverse outcome, a death, occurred in the 24 off-pump patients reporting (4.2%). Histologic analyses showing the number of filters successfully extracting particles, the number of particles and total particulate surface area per filter, and the ranges are shown in below. Histologic Finding Cohort 1 Cohort 2 Cohort 3 Filters with particles 98% 100% 100% Mean # of particles 8.5 9.6 5.6 Range # of particles 0-76 1-29 2-13 Mean surface area (mm2) 11.8 18.4 6.1 Range surface area (mm2) 0-171 0.5-61 0.2-14",
            "output": [
                "Does intraaortic filtration capture particulate debris in OPCAB cases using anastomotic devices?"
            ]
        },
        {
            "id": "task847-1f6d6febc814480e801212ed75535399",
            "input": "AIM, MATERIAL AND METHODS: Endodontic treatment of a total of 303 teeth with pulpitis and periodontitis was performed with a new calcium-carbamide-formaldehyde paste. In three children with fractured teeth with complications, the applied treatment was combined (2 teeth with apical osteotomy and 1 with cystectomy). Control examinations were carried out at months 6, 12 and 24 and clinically healthy teeth and teeth with complications were registered.', 'In the pulpitis group the clinically healthy teeth were 97.55% +/- 1.08 at the 6th month; 96.85% +/- 1.26 at the 12th month and 92.92% +/- 2.41 at the 24th month. In teeth with periodontitis 91.56% +/- 3.05 were clinically healthy at the 6th month; 93.83% +/- 2.67 at the 12th month and 98.03% +/- 1.98 at the 24th month. No statistical significance of the differences between pulpites and periodontites was found (P > 0.05). Recovery of the bone structure was observed in the teeth with combined endodontic and surgical treatment at the 12th month.",
            "output": [
                "Do endodontic treatment of permanent teeth in children with a new calcium-carbamide-formaldehyde paste?"
            ]
        },
        {
            "id": "task847-0a05e77f6e564c4781de2a36eeb1f957",
            "input": "To examine whether the noninvasive technique of blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) can detect changes in renal medullary oxygenation following administration of a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). Hypertension is associated with endothelial dysfunction and is characterized by a lack of response to endothelial-dependent vasoactive substances, including nitric oxide synthase inhibitors. We hypothesized that the magnitude of the change would be reduced in the kidneys of hypertensive subjects relative to normal controls.', 'To test this hypothesis, data were obtained in spontaneously hypertensive rats (SHR, n = 6). Wistar-Kyoto rats (WKY, n = 7) were used as normotensive controls.', 'As expected, WKY rats showed a significant response to L-NAME (R(2)* increasing from 23.6+/-1.5 Hz to 32.5+/-2.2 Hz, P < 0.05), while SHR exhibited a minimal change in medullary oxygenation (R(2)* measuring 31.9+/-2.8 Hz pre- and 35.5+/-2.2 Hz post-L-NAME). The baseline R(2)* in SHR is found to be comparable to post-L-NAME values in WKY rats, suggesting a basal deficiency of nitric oxide in SHR.",
            "output": [
                "Do kidneys in hypertensive rats show reduced response to nitric oxide synthase inhibition as evaluated by BOLD MRI?"
            ]
        },
        {
            "id": "task847-17ca93decaa44c1e8f039c1cccbf8111",
            "input": "To evaluate the effects of COX-1 and/or COX-2 inhibition in a model of chronic esophagitis in rabbits.', 'Both high- and low-grade esophagitis were induced in rabbits by the perfusion of acidified pepsin. Rabbits were treated with either a selective COX-2 inhibitor (DFU[3-(3-Fluorophenyl)-4-(4-Methanesulfonyl)-5,5-Dimethyl-5H-Furan-2-One];30 mg/Kg/day), a nonspecific COX inhibitor (indomethacin; 2 mg/Kg/day), or a COX-1 preferential inhibitor (piroxicam; 2 mg/Kg/12 h).', 'Prostaglandins are derived from COX-1 activity in the normal esophagus. Both low- and high-grade esophagitis are associated with a progressive increase of COX activity, which is partially dependent on the COX-2 isoform. DFU reduced muscosal damage in both models of esophagitis. However, indomethacin did not affect significantly mucosal damage, and piroxicam increased damage in low-grade esophagitis.",
            "output": [
                "Is selective COX-2 inhibition associated with decreased mucosal damage induced by acid and pepsin in rabbit esophagitis?"
            ]
        },
        {
            "id": "task847-c4b1d66791f744b8aad908c770004c1a",
            "input": "We have previously shown that blood transfusion in the first 24 hours is an independent predictor of mortality, intensive care unit (ICU) admission, and increased ICU length of stay in the acute trauma setting when controlling for Injury Severity Score, Glasgow Coma Scale score, and age. Indices of shock such as base deficit, serum lactate level, and admission hemodynamic status (systolic blood pressure, heart rate) and admission hematocrit were considered potential confounding variables in that study. The objectives of this study were to evaluate admission anemia and blood transfusion within the first 24 hours as independent predictors of mortality, ICU admission, ICU length of stay (LOS), and hospital LOS, with serum lactate level, base deficit, and shock index (heart rate/systolic blood pressure) as covariates.', 'Prospective data were collected on 15,534 patients admitted to a Level I trauma center over a 3-year period (1998-2000) and stratified by age, gender, race, Glasgow Coma Scale score, and Injury Severity Score. Admission anemia and blood transfusion were assessed as independent predictors of mortality, ICU admission, ICU LOS, and hospital LOS by logistic regression analysis, with base deficit, serum lactate, and shock index as covariates.', 'Blood transfusion was a strong independent predictor of mortality (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.82-4.40; p < 0.001), ICU admission (OR, 3.27; 95% CI, 2.69-3.99; p < 0.001), ICU LOS (p < 0.001), and hospital LOS (Coef, 4.37; 95% CI, 2.79-5.94; p < 0.001) when stratified by indices of shock (base deficit, serum lactate, shock index, and anemia). Patients who underwent blood transfusion were almost three times more likely to die and greater than three times more likely to be admitted to the ICU. Admission anemia (hematocrit < 36%) was an independent predictor of ICU admission (p = 0.008), ICU LOS (p = 0.012), and hospital LOS (p < 0.001).",
            "output": [
                "Is blood transfusion , independent of shock severity , associated with worse outcome in trauma?"
            ]
        },
        {
            "id": "task847-51cf22adcae549829ced1fa1ea7afab1",
            "input": "To determine xanthine oxidase and superoxide dismutase activities, lipid peroxidation, protein carbonylation, and total radical-trapping antioxidant parameter in survivors and nonsurvivors patients with severe burn injury.', 'Prospective, comparative observational study in an intensive care unit, burn division, in a trauma hospital.', 'Twenty-five consecutive patients who met the established criteria for severe burn injury (total burn surface area of more than 30%).', 'Plasma thiobarbituric acid reactive species and protein carbonyls levels were significantly higher in nonsurvivors than in survivors at 0 and 6 h. Elevated xanthine oxidase activity at 0 h was associated with adverse outcome after burn injury. In contrast, plasma superoxide dismutase activity and total radical-trapping antioxidant parameter did not differ significantly between nonsurvivors and survivors at any time point.",
            "output": [
                "Do plasma oxidative parameters and mortality in patients with severe burn injury?"
            ]
        },
        {
            "id": "task847-f5077aac429e49c29846ae1b0b977ab9",
            "input": "Previous studies have shown a relationship between intima-media thickness (IMT) of the common carotid artery and coronary artery disease (CAD). The role of IMT in the prediction of significant CAD has not been established.', 'To investigate the diagnostic accuracy of IMT measurement and the detection of carotid plaques in relation to cardiovascular risk factors in the prediction of significant CAD.', 'One hundred and seventy patients (121 men and 49 women; average age 58 +/- 11 years) undergoing selective coronary angiography were examined by carotid ultrasound. IMT was measured. Plasma lipid concentrations and other risk factors were determined.', 'Angiographically proven significant CAD was found in 138 (81%) of all patients. Carotid plaques were detected in 98 (58%) of all patients. Presence of carotid plaques in common carotid artery (P<0.001) and male sex (P<0.005) were found to be categorical risk factors for significant CAD but in multiple regression analysis only age (P=0.15), IMT (P<0.01), high density lipoprotein (HDL) cholesterol (P=0.02) and, less significantly, total cholesterol (P=0.09) were found to be independent parameters for the prediction of significant CAD. IMT of 0.75 mm was determined as a cut-off point for the detection of significant CAD (sensitivity 78%, specificity 79%, positive predictive value 95%, negative predictive value 41%, odds ratio 12.9, 95% CI 3.5 to 47.6).",
            "output": [
                "Is intima-media thickness of the common carotid artery the significant predictor of angiographically proven coronary artery disease?"
            ]
        },
        {
            "id": "task847-33ecdb7a785547bfb6383f46c09f41ac",
            "input": "Executive cognitive functioning (ECF), a construct that includes cognitive abilities such as planning, abstract reasoning, and the capacity to govern self-directed behavior, has been recently researched as an antecedent to many forms of psychopathology and has been implicated in alcohol-related aggression. This study was designed to examine whether differential ECF impairments can be noted on the ascending versus the descending limbs of the blood alcohol concentration curve.', 'Forty-one male university students participated in this study. Twenty-one subjects were given 1.32 ml of 95% alcohol per kilogram of body weight, mixed with orange juice, and the remaining 20 were given a placebo. Participants were randomly assigned to either an ascending or descending blood alcohol group and were tested on six tests of ECF on their assigned limb. Subjective mood data were also collected.', 'Intoxicated participants on both limbs demonstrated ECF impairment; the descending-limb group showed greater impairment than their ascending-limb counterparts. Intoxicated subjects were significantly more anxious at baseline than placebo subjects. The introduction of this covariate nullified any significant differences in subjective mood found on either limb of the blood alcohol concentration curve, but ECF impairments remained robust.",
            "output": [
                "Does alcohol affect executive cognitive functioning differentially on the ascending versus descending limb of the blood alcohol concentration curve?"
            ]
        },
        {
            "id": "task847-f8b738ab60df4e5ab50e2aeaa4eba2c5",
            "input": "Recent studies have implicated central nicotinic cholinergic receptor systems in the reinforcing properties of alcohol. In laboratory animals, mecamylamine, a central nicotinic receptor antagonist, reduces the consumption of and preference for alcohol. This study investigated the effect of mecamylamine on the subjective responses to alcohol in humans. It was hypothesized that mecamylamine (7.5 and 15 mg) would attenuate the stimulant-like subjective effects of alcohol (0.8 g/kg) and decrease the self-reported desire to consume additional alcohol beverages.', 'Fourteen male and 13 female nonsmokers participated in 6 laboratory sessions. During each session, subjects received, in randomized order under double-blinded conditions, a capsule containing mecamylamine (7.5 or 15 mg) or placebo followed by a beverage containing alcohol (0.8 g/kg) or placebo. Physiologic and subjective-effect measures were taken at 30-min intervals for 2 hr after beverage consumption.', 'Mecamylamine attenuated the stimulant and euphoric effects of alcohol and reduced the self-reported desire to consume additional alcohol beverages. This effect was most pronounced in men, even though women exhibited greater physiologic reactions to mecamylamine.",
            "output": [
                "Does mecamylamine attenuate the subjective stimulant-like effects of alcohol in social drinkers?"
            ]
        },
        {
            "id": "task847-913528b7018b4bf8bbe452da57b6b185",
            "input": "Decreased sensitivity to alcohol has been demonstrated to be a predictor of alcoholism in humans, and variation in the gene-linked polymorphic region of the serotonin transporter (5-HTTLPR) is associated with the response to the motor-impairing effects of alcohol. In a nonhuman primate model of excessive alcohol intake, we have shown that decreased serotonin turnover is associated with both lower initial sensitivity to alcohol and higher prospective alcohol consumption using rhesus macaques. In addition, we have demonstrated that macaques separated from their mothers and reared in peer-only groups are more likely to consume alcohol as adults.', 'To examine the relationship between serotonin transporter genotype, early rearing experience, and initial sensitivity to alcohol, peer- and mother-reared, adolescent, alcohol-naive rhesus macaques (n = 123) were rated for intoxication after intravenous administration of ethanol (2.2 g/kg and 2.0 g/kg for males and females, respectively) during two testing periods. Serotonin transporter (rh5-HTTLPR) genotype was determined using polymerase chain reaction followed by gel electrophoresis, and data were analyzed using ANOVA and the Mann-Whitney U test.', 'Our analyses demonstrate an effect of serotonin transporter gene variation on ethanol sensitivity, such that animals homozygous for the l allele exhibited decreased sensitivity to the ataxic and sedating effects of alcohol. This effect remained after correction for blood ethanol concentrations and birth cohort. When animals were segregated according to rearing condition, serotonin transporter gene variation predicted intoxication scores among peer-reared animals.",
            "output": [
                "Is serotonin transporter gene variation associated with alcohol sensitivity in rhesus macaques exposed to early-life stress?"
            ]
        },
        {
            "id": "task847-f1261f58c5d8436cb725fee6fed1577b",
            "input": "Plague is a severe, highly communicable bacterial disease caused by Yersinia pestis. It is still endemic in more than 20 countries worldwide. Although known as a devastating disease for centuries, laboratory confirmation of clinical suspected cases is still problematic. No standardized and internationally approved test system is commercially available. The aim of this study was the introduction and evaluation of a combination of immunomagnetic separation and flow cytometry for the serodiagnosis of human plague.', 'Paramagnetic polystyrene beads were coated with purified F1 capsular antigen (F1 CA) and reacted with sera from plague patients, from 26 laboratory personnel vaccinated against plague and from 102 healthy blood donors (HBD). After incubation with fluorescein isothiocyanate-conjugated anti-human rabbit IgG, particle-associated fluorescence was detected by flow cytometry.', 'Anti-F1 CA antibodies could be demonstrated in all patients with bacteriologically confirmed plague and in 22 sera (84.6%) from vaccinees. Only one serum in the HBD group showed a weakly positive reaction. The total assay time was less than 2 h.",
            "output": [
                "Do serodiagnosis of human plague by a combination of immunomagnetic separation and flow cytometry?"
            ]
        },
        {
            "id": "task847-3c719f1d727e455d88450c4397877b93",
            "input": "Malnutrition impairs host immunity, resulting in high mortality and morbidity, secondary to infections. Nuclear factor kappaB (NFkappaB) plays a critical role in host defense, but how quickly refeeding normalizes the impaired NFkappaB activity in peritoneal resident cells (PRCs) is unknown. Our aim was to investigate the effects of 1-day ad libitum refeeding on severe diet restriction-induced NFkappaB activity in PRCs.', 'Mice received chow, 146 g/kg per day (ad libitum) or 36.5 g/kg per day (severe diet restriction), for 7 days. One-half the mice in the diet-restricted group were then fed ad libitum for 1 day (refeeding). PRCs were harvested by peritoneal lavage. After incubation with tumor necrosis factor-alpha (TNF-alpha), nuclear translocation of NFkappaB in PRCs was investigated using laser scanning cytometry.', 'The main subpopulation of PRCs was macrophages in all groups. Mean fluorescence intensity over the nuclear area at 0 or 100 ng/mL of TNF-alpha was 16 +/- 2 or 31 +/- 8* in the ad libitum, 20 +/- 4 or 19 +/- 3 in the severe diet-restricted, and 20 +/- 4 or 30 +/- 5* in the refeeding group, respectively (*p < .05 versus 0 ng/mL of TNF-alpha in each group versus 100 ng/mL of TNF-alpha in diet-restricted group). Cytoplasmic accumulation of NFkappaB was significantly increased after TNF-alpha stimulation in the refed group but not in the ad libitum group.",
            "output": [
                "Does brief refeeding rapidly reverse dietary restriction-induced nuclear factor-kappaB downregulation in peritoneal resident cells?"
            ]
        },
        {
            "id": "task847-e2d8b55f8c2246789f063f2e6f20eac8",
            "input": "The goals of the current study were to examine the incidence and severity of toxicity resulting from dexamethasone and prednisone during induction therapy for children with precursor B-cell acute lymphoblastic leukemia (ALL) and to determine whether the addition of daunomycin affected toxicity.', 'Medical records of patients with precursor B-cell ALL from January 1996 through June 2000 were reviewed retrospectively for toxicity during the 4-week induction phase and the 2 weeks after the induction phase.', 'One hundred seventy-six patients age < 14 years were diagnosed with precursor B-cell ALL from January 1996 through June 2000. Of the 156 evaluable patients, 106 were treated with prednisone and 50 with dexamethasone. Fifty-two patients received steroids, L-asparaginase, and vincristine, whereas 104 high-risk patients received daunomycin in addition to these 3 agents. The incidence of gastritis was significantly higher among patients receiving dexamethasone (P = 0.01); incidence rates of hyperglycemia, hypertension, and myopathy were similar for all treatment groups. Dexamethasone led to more weight gain than did prednisone (+11.9% vs. +5.4%; P = 0.002). Serious infections were observed in 27 (25.5%) and 18 (36%) patients receiving prednisone and dexamethasone, respectively (P < or = 0.2). Five patients, four of whom received prednisone and one of whom received dexamethasone, died of infection. The addition of daunomycin to treatment regimens increased overall toxicity (P < 0.01). When daunomycin was included in treatment regimens, toxicity was greater among patients receiving dexamethasone; in contrast, when daunomycin was not included, toxicity was equal for both treatment groups. Regardless of daunomycin use, there was no difference in the incidence of serious infection between the two groups. ALL treatment was not compromised by steroid-related toxicity in either group.",
            "output": [
                "Is dexamethasone-associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia augmented by concurrent use of daunomycin?"
            ]
        },
        {
            "id": "task847-ca63e8bb872f4baaa3d593087cfb54ba",
            "input": "A defect in retinal pigment epithelial (RPE) cells may cause dysfunction of the neural retina, so rapid recovery of differentiated RPE cells is required after RPE injury. We investigated the effect of hepatocyte growth factor (HGF) on wound healing in RPE cells.', 'Confluent monolayers of bovine RPE cells were denuded, and the cells were allowed to recover in the presence or absence of HGF. The effect of HGF on RPE cell proliferation was evaluated by a 3-(4;5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetraz olium assay. In a migration assay, mitomycin C was used to inhibit proliferation, and the number of migrated cells was counted. The signaling pathways involved were examined using inhibitors of mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 (PI3) kinase and protein kinase C pathways.', 'At 80 ng/mL, HGF stimulated the wound closure of RPE monolayers and rendered the restituted cells more epithelioid in shape. HGF at 10 ng/mL stimulated RPE cell migration the most, whereas 80 ng/mL of HGF inhibited migration, but stimulated proliferation the most. In particular, PI3 kinase and MAPK inhibitor inhibited PRE cell migration and proliferation, respectively.",
            "output": [
                "Does hepatocyte growth factor stimulate proliferation and migration during wound healing of retinal pigment epithelial cells in vitro?"
            ]
        },
        {
            "id": "task847-11e669f24d4043ae8aa0aebf9a2d3195",
            "input": "Antibodies to hepatitis C virus (anti-HCV) have typically been detected by enzyme immunoassay (EIA). A chemiluminescence assay (CA) for anti-HCV is now commercially available.', 'We compared the positive rate for a CA in a HCV screening program for veterans with historical rates obtained with EIA. We also compared results in 2824 samples tested by both methods and assessed the significance of low signal-to-cutoff (S/C) ratios.', 'The frequency of CA-positive results was significantly lower than with EIA (12.6% vs 16.0%; P <0.0001). The frequency of low S/C ratios was also significantly lower with CA (11.5% vs 20.0%; P <0.0001). Among low-positive values, samples positive by CA were significantly less likely to be recombinant immunoblot assay (RIBA)-negative (64% vs 84%; P <0.0005). In parallel testing, results for 111 samples (3.9%) were discrepant between the two assays; all but 6 had low S/C ratios, and confirmatory testing was performed on all but 8 samples. Of 56 EIA-positive, CA-negative samples tested by RIBA, only 1 was positive. Of 24 CA-positive, EIA-negative samples, 62% were RIBA-negative. Using a negative RIBA result as an indication of false-positive anti-HCV results, the positive predictive value of EIA was 93% compared with 98% with CA. HCV RNA was positive in 90% of samples high-positive by both CA and EIA. Only 2 of 30 (7%) low-positive CA samples were RNA-positive.",
            "output": [
                "Does chemiluminescence assay improve specificity of hepatitis C antibody detection?"
            ]
        },
        {
            "id": "task847-a4a058dd3bfa49c492905d1356ae3762",
            "input": "To ascertain whether inoculation of lipopolysaccharide (LPS) into the mouse cochlea might induce enhancement of DNA binding activity of NK-kappa B and to establish a positive model of NF-kappa B activation in the cochlea.', 'Two groups of CBA mice were transtympanically injected either with 10 micrograms of LPS or an equal volume of saline. The nuclear proteins of the cochlea were extracted, quantitated and bound with 32P-radiolabeled oligonucleotide probe for NF-kappa B. The bound and free probes were separated by electrophoresis on a 4.5% native polyacrylamide gel. Supershift assays were carried out using the antibodies against NF-kappa B subunit P65 and P50.', 'The radiolabeled probe bound differently to nuclear extracts from the LPS-treated and the saline-treated mouse cochleae, showing that LPS inoculation significantly increased NF-kappa B binding activity. Supershift analysis demonstrated that the enhancement of DNA binding activity was related to both P65 and P50 subunits.",
            "output": [
                "Does [ Lipopolysaccharide enhance DNA binding activity of nuclear factor-kappa B in the mouse cochlea ]?"
            ]
        },
        {
            "id": "task847-7551c124561a4601878be76bc92363ed",
            "input": "Our objective was to determine whether adenosine-induced ischemia exerts a delayed cardiac protective effect in patients with stable effort angina ischemic heart disease.', 'The study group was comprised of 32 patients (men) with symptoms of stable effort angina, aged 38-65 years (Group 1), and 18 clinically healthy subjects (3 women, 15 men), aged 35-55 years (Control group). The study protocol included baseline ECG and treadmill echocardiogram (ET1); ECG and adenosine echocardiogram performed 7 days after ET1; repeated exercise test exactly 24 h after adenosine infusion (ET2). Increases in heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure, maximum ST-segment depression (max IST) and total ST-segment depression (SIST) on ECG were compared, as well as left ventricular end-diastolic volume (LVEDV), end-systolic (LVESV) volume, ejection fraction (EF), and wall motion synergy index (WMSI).', 'No statistically significant differences were found in the increased values of the investigated electrocardiographic and echocardiographic parameters in either group on either exercise test. The only positive trend was observed in LVEDV. In Group 1 LVEDV increased significantly from rest values during ET1, whereas during ET2 LVEDV did not change.",
            "output": [
                "Does adenosine-activated myocardial ischemia induce delayed preconditioning?"
            ]
        },
        {
            "id": "task847-4c4dd5ecee4a4d14842d1a1e56aa1547",
            "input": "Dysplastic nodules (DN) may be divided into high-grade and low-grade, and the former has been known as a precancerous or borderline lesion. Recently many morphological characteristics concerning these types of DN have been reported. In the present study we attempted to evaluate the scirrhous change in DN as an indicative feature of high-grade DN, based on the morphological and cell-kinetic analyses using immunohistochemical stains for Ki-67.', \"We reviewed 35 livers with DN and selected 15 DN with scirrhous change. We stained DN-bearing sections of each case with hematoxylin and eosin, trichrome, reticulin and Perls' stain. We tried to subclassify and characterize the scirrhous change according to the fibrosis pattern. We also stained with Ki-67 immunohistochemically to assess the proliferative activity of DN with scirrhous change.\", 'We found two types of scirrhous change, that is, pericellular and stellate. The pericellular type was related to the Mallory body-forming cholestatic degeneration, whereas the stellate type was associated with extensive portal fibrosis probably induced by ischemic damage. Among DN with scirrhous change, high-grade DN comprised five nodules (33%) and there were 10 (67%) low-grade nodules. There was no significant relationship between the presence or the types of scirrhous change and the grade of DN. The significant differences of Ki-67 labeling indices between types of scirrhous change were not shown in this study. We also could not find the differences between Ki-67 labeling indices of scirrhous DN (high and low grades) and those of surrounding regenerative nodules.",
            "output": [
                "Do scirrhous changes in dysplastic nodules indicate high-grade status?"
            ]
        },
        {
            "id": "task847-3b9121159de2434ba3479fe56f14e109",
            "input": "Correlation between the gross classification of hepatocellular carcinoma (HCC) and its vascular invasion or intrahepatic metastasis has been reported previously. Because E-cadherin-mediated epithelial cell-to-cell adhesion is thought to suppress cancer cell invasion, the present study was performed to analyze the correlation between E-cadherin expression and the gross classification of HCC.', 'Thirty-six resected solitary HCC <6 cm in diameter were each classified as single nodular type (type 1), single nodular with extranodular growth type (type 2) or contiguous multinodular type (type 3), and the clinicopathological and prognostic differences between type 1 HCC and the other types were analyzed. The expression of E-cadherin in each tumor was examined by immunoblotting and immunohistochemical analysis.', 'Vascular invasion and microscopic intrahepatic metastasis were observed more frequently in types 2 and 3 (61%) than in type 1 (13%) HCC. Immunoblot analysis indicated that the relative level of E-cadherin expression in cancerous tissue was significantly lower in type 2 and 3 (0.75 +/- 0.49) than in type 1 (1.46 +/- 0.79) HCC. Immunohistochemical examination revealed decreased and partially absent E-cadherin expression in the tumorous area of type 2 and 3 HCC. The recurrence-free survival rate was higher for patients with type 1 HCC than for those with the other types.",
            "output": [
                "Does gross appearance of hepatocellular carcinoma reflect E-cadherin expression and risk of early recurrence after surgical treatment?"
            ]
        },
        {
            "id": "task847-87f57d5e59b94aff87f6e331acdc512f",
            "input": "Relaxation of pelvic ligaments may facilitate parturition in certain animal species. Biomechanical properties of pelvic connective tissue may also influence progress of labour in the human female. This study was designed to test whether peripheral joint mobility or pelvic organ mobility as measures of connective tissue biomechanical properties are associated with progress in labour and delivery mode.', 'Prospective clinical observational study.', 'Tertiary obstetric service.', '200 nulliparous women recruited in antenatal clinic.', 'Translabial ultrasound was used to obtain data on third trimester pelvic organ mobility. Upper limb joint mobility was assessed clinically.', 'Gestational length, length of first and second stage of labour, delivery mode.', 'Pelvic organ mobility was significantly associated with total length of second stage (P = 0.034 to P = 0.002). This was mainly due to the length of passive, not active second stage. There also was a statistically significant association between delivery mode and pelvic organ descent (P = 0.007 to P = 0.001), with the lowest mobility seen in women who required a Caesarean section in second stage. Joint mobility did not correlate with delivery data.",
            "output": [
                "Is antenatal pelvic organ mobility associated with delivery mode?"
            ]
        },
        {
            "id": "task847-74656a9208eb4e3899b2fb61c25e5ccb",
            "input": "Alefacept, human LFA-3/IgG1 fusion protein, is a novel biological agent currently being developed for the treatment of chronic plaque psoriasis. Alefacept selectively reduces the memory-effector T cells that have been implicated in the pathogenesis of the disease; as a result, alefacept is classified as a therapy that induces remission (so-called 'remittive' therapy). In a previously published randomized, placebo-controlled phase II study of intravenous alefacept in 229 patients with chronic plaque psoriasis, clinical improvement was observed during dosing as well as in the postdosing follow-up period.\", 'To assess the remission period following alefacept therapy.', \"The time before re-treatment was required was measured in patients who were 'clear' or 'almost clear' of disease according to a physician global assessment at the end of the follow-up phase.\", 'In these patients, responses were sustained for a median of 10 months, and for up to 18 months. No patient reported disease rebound after cessation of alefacept.",
            "output": [
                "Does alefacept therapy produce remission for patients with chronic plaque psoriasis?"
            ]
        },
        {
            "id": "task847-99d0561878a94528b86e628ee4b7f2cc",
            "input": "To assess the impact of providing research feedback to retinoblastoma survivors or their parents regarding the risk of second cancers.', 'A four-page survey was sent to 801 retinoblastoma survivors and 55 parents to ascertain their reactions to a \"results-letter.\" The \"results-letter\" provided feedback from a study indicating that retinoblastoma survivors may be at increased risk of second cancers.', 'Three hundred and thirty-nine (339) retinoblastoma survivors and 43 parents responded to the survey. Eighty-four percent (84%) of respondents found the \"results-letter\" \"very\" to \"extremely\" understandable and 72% found it \"very\" to \"extremely\" useful. Participants scored \"very\" to \"extremely\" to the following emotions: frightened = 28%, anxious = 27%, sad = 25%, overwhelmed = 15%, angry = 11%, and guilty = 6%. Five (1.4%) respondents stated that they would have preferred not to receive the results. Responses did not vary significantly between survivors with different risks of second cancers. No significant differences were observed between males and females. However, parents were significantly more likely to report feelings of anxiety, guilt, anger, being overwhelmed, and frightened compared to adult retinoblastoma survivors (P < 0.05). Individuals with less than a college education were significantly more sad, angry, overwhelmed, and frightened by the information than individuals with a college degree or higher (P < 0.05). Eighteen percent (18%) of all respondents shared the feedback with their physician. The method of choice for receiving results was by letter with contact names and phone numbers.",
            "output": [
                "Does impact on survivors of retinoblastoma when informed of study result on risk of second cancers?"
            ]
        },
        {
            "id": "task847-b87832ca2d4d45a2b386a6f395e7aa11",
            "input": "This evaluation was conducted as part of a protocol entitled Evaluation of the Menicon Z Rigid Gas Permeable Contact Lens for up to 30 Days Extended Wear. The purpose of the protocol was to compare corneal endothelial morphology changes after wearing rigid gas-permeable (RGP) Menicon Z contact lenses, continuously for up to 30 days, with ACUVUE (Johnson & Johnson Vision Care) hydrogel contact lenses, worn for up to 6 nights of extended wear.', 'Sixty patients, who were adapted to RGP daily wear and soft contact lens daily wear, were recruited at two study sites. The thirty subjects who wore RGP daily wear lenses were fitted with the Menicon Z (tisilfocon A, oxygen permeablility [Dk] = 163) RGP contact lens comprised the test group. The control group subjects (n = 30 former users of daily wear soft contact lenses) were fitted with ACUVUE (etafilcon A, Dk = 28) hydrogel contact lenses. After a 2-week adaptation period of daily wear, subjects began extended wear. Endothelial imaging was performed at the two study sites in this multicenter study (University Hospitals of Cleveland/Case Western Reserve University Department of Ophthalmology [CWRU] and The Ohio State University [OSU]). The hydrogel lens group was instructed to wear their lenses for 7 days and 6 nights before discarding the lenses and to sleep with no lenses on the seventh night. The RGP group was permitted to wear the lenses for up to 30 days and 29 consecutive nights before removing the lenses for cleaning and overnight soaking.', \"CWRU had 24 patients (12 soft contact lens and 12 rigid contact lens) and OSU had 21 patients (12 soft contact lens and 9 rigid contact lens) who completed the study and were included in the analyses. Patients who were withdrawn from the study at CWRU included one RGP patient dropped out because of pregnancy; one RGP patient developed vascularized limbal keratitis and discomfort; one could not be fitted with a bitoric RGP; two soft lens patients moved from the area, and one dropped out because of dry eyes. At OSU, four patients dropped out due to discomfort (two in each lens type);one moved from the study area; one decided not to participate soon after the consent visit; one had worries of reduced vision at 6 months; one subject's attitude changed prior to the 6 month visit; and one subject was withdrawn for reasons of poor study schedule compliance.",
            "output": [
                "Does corneal endothelial morphology result in the Menicon Z 30-day continuous-wear contact lens clinical trial?"
            ]
        },
        {
            "id": "task847-52216ea381f24814a9fb9306442d5062",
            "input": "Viral infections are associated with both mild and severe exacerbations of asthma and may therefore be associated with asthma death. As such we hypothesized that it might be possible to detect rhinovirus (RV), the virus most frequently implicated in acute asthma, in lung tissue from patients who died from asthma.', 'We studied archival, wax-embedded lung tissue obtained postmortem from: (i) patients who died from asthma (n = 12), (ii) asthma patients with non-asthma-related death (n = 3), and (iii) non-asthmatic individuals who died from unrelated causes (n = 3). A validated reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect RV. To confirm RNA preservation, RT-PCR was used to detect expression of the constitutive gene adenine-phosphoribosyl-transferase (APRT). Sensitivity of the assay was assessed using wax-embedded RV-infected cells.', 'Sensitivity of RT-PCR for RV in wax-embedded sections was similar to previous studies (approximately 100 viral copies). Specimens used for study were predominantly of alveolar and small airway origin (< 2 mm). All tissues examined were negative for the presence of RV mRNA and positive for APRT mRNA.",
            "output": [
                "Is rhinovirus detectable in peripheral lung tissue after asthma death?"
            ]
        },
        {
            "id": "task847-d94f267364ce4ff0b0d291e25931213c",
            "input": "Fibroblast-like synovial cells (FLS) can be cultured and expanded in vitro in monolayer. Little is known about the growth characteristics of FLS derived from different patients.', 'To study FLS cultures, with particular attention to differences in growth rate of FLS from patients with rheumatoid arthritis (RA) and from other arthritic patients. Additionally, to analyse the influence of methotrexate (MTX) treatment, patient age, and disease duration on FLS growth characteristics.', 'FLS were isolated from needle arthroscopy biopsy specimens. Twenty four patients (11 RA, 8 spondyloarthropathy, 1 osteoarthritis, and 4 undifferentiated arthritis) were studied. FLS population doubling time was determined between passage 2 and passage 5. Differences in population doubling time between RA and non-RA FLS and between FLS from patients receiving MTX and those not receiving this drug were analysed. In addition, possible correlations between FLS population doubling time and patient age or disease duration were examined.', 'In vitro monolayer FLS cultures from needle arthroscopy biopsy specimens showed linear growth characteristics. Cell growth rate was not correlated with type of disease. Cells from patients undergoing treatment with MTX showed a longer population doubling time than FLS from patients not receiving this drug (Mann-Whitney test, p<0.05). No correlation was found with patient age or disease duration.",
            "output": [
                "Is in vitro growth rate of fibroblast-like synovial cells reduced by methotrexate treatment?"
            ]
        },
        {
            "id": "task847-bf60b488d95e4fd091b1455eaa12d317",
            "input": "Systemic lupus erythematosus (SLE) is characterised by the presence of antibodies to double stranded DNA (dsDNA), which are involved in the pathogenesis of SLE. Previous studies showed that at least two thirds of patients develop a clinical relapse within six months after a significant rise in the anti-dsDNA level, and most relapses were prevented by the administration of corticosteroids at the time of the rise.', 'To determine whether mofetil mycophenolate (MMF) can prevent a clinical relapse without the side effects associated with corticosteroids.', '36 patients with SLE were examined monthly to determine whether a rise in anti-dsDNA level had occurred. A rise was defined as an increase of 25% of the level of the previous sample of at least 15 IU/ml within a four month period. After a rise patients were treated with MMF 2000 mg daily for six months. Patients were monitored monthly for the occurrence of a clinical relapse and to assess the serological activity and state of activation of CD4+, CD8+, and CD19+ lymphocyte subsets.', 'Anti-dsDNA rose in 10 patients. Treatment with MMF was started in all these patients, and after six months no clinical relapse had occurred. Side effects were minimal. Antibodies to dsDNA decreased during the treatment (p<0.001), associated with a decrease in the state of activation of CD19+ lymphocytes. No changes were found in the state of activation of CD4+ or CD8+ lymphocyte subsets.",
            "output": [
                "Does mycophenolate mofetil prevent a clinical relapse in patients with systemic lupus erythematosus at risk?"
            ]
        },
        {
            "id": "task847-d3a01ca7f8bb4a13aa2d00b40296f7c2",
            "input": "Paradoxical embolism via persistent foramen ovale (PFO) is suspected to be a frequent cause of stroke in younger patients. We investigated whether the prevalence of the risk factors for venous thrombosis factor V Leiden (FVL) and prothrombin G20210A mutation (PT G20210A) is increased in this group of patients.', 'We examined FVL and PT G20210A mutation in 220 patients (group 1) with cerebral ischemia associated with a PFO and without other etiology, in 196 patients with cerebral ischemia of an etiology other than PFO (group 2), and in 362 healthy subjects (group 3) from the same region in Germany.', 'Heterozygosity for the PT G20210A mutation was more common in group 1 (5.0%) than in group 3 (1.4%; sex- and age-adjusted odds ratio 3.66; 95% CI 1.25-10.75; p = 0.01). By contrast, the mutation was not more common in group 2 (2.6%; odds ratio 1.50; 95% CI 0.42-5.41; p = 0.5). Prevalences of FVL were not different between groups.",
            "output": [
                "Is prothrombin G20210A mutation , but not factor V Leiden , a risk factor in patients with persistent foramen ovale and otherwise unexplained cerebral ischemia?"
            ]
        },
        {
            "id": "task847-d55806716d044367b1b100c213313908",
            "input": "This study tests the hypothesis that Medicare beneficiaries at high risk of foot complications who are mailed a motivational brochure describing the Medicare diabetes-related therapeutic footwear benefit will increase their therapeutic footwear-related Medicare claims.', 'In this quasi-experimental study, a motivational brochure was mailed in the summer of 1997 to 5,872 Medicare beneficiaries in Washington, Alaska, and Idaho who were identified as being at high risk for foot-related claims on the basis of their prior Medicare claims history. Beneficiaries were identified through footwear claims made in these states-and also in three comparison states (Oregon, Montana, and Wyoming)-during the 18 months before and after the mailing. Linear regression was used to compare the number of persons making claims in the intervention states with the comparison states before, at the time of, and after the mailing.', 'Before the intervention, the number of persons making claims was increasing in the non-intervention states and decreasing in the intervention states. During the first month after the intervention mailing, the number of persons making claims remained nearly the same in non-intervention states, but increased 13 persons per month in intervention states (95% CI 3.5-11 persons/month). After the intervention, the number of persons making claims continued to increase similarly in both intervention and non-intervention states.",
            "output": [
                "Do motivational brochures increase the number of medicare-eligible persons with diabetes making therapeutic footwear claims?"
            ]
        },
        {
            "id": "task847-a3826e75b80a419c81c196894e2ecb09",
            "input": "To test whether weight loss may improve endothelial dysfunction in human obesity, we recruited 28 healthy obese subjects, aged 30-46 years, with BMI 30-43 kg/m(2).', 'Endothelium-dependent and -independent vasodilation were investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh; 7.5, 15, and 30 microg x ml(-1) x min(-1)) and sodium nitroprusside (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)). Insulin resistance was estimated by homeostasis model assessment (HOMA). Weight loss was obtained by caloric restriction and physical activity.', 'We observed a significant reduction in BMI (from 33.1 +/- 4.2 to 27.5 +/- 4.5 kg/m(2), -16.9%, P < 0.0001) and in waist circumference (from 108.2 +/- 12.1 to 96.8 +/- 12.9 cm, -10.5%, P < 0.0001). Weight loss was also associated with a significant increase in ACh-stimulated forearm blood flow (FBF), from 7.4 +/- 2.8 to 12.9 +/- 3.4 ml. 100 ml(-1) of tissue x min(-1) kg/m(2) (P < 0.0001). Multivariate regression analysis demonstrated that the only independent predictor of FBF was HOMA, accounting for 44.5% of the variation, whereas the addition of BMI explained another 2.3% of the variation.",
            "output": [
                "Does weight loss in combination with physical activity improve endothelial dysfunction in human obesity?"
            ]
        },
        {
            "id": "task847-7fb8d1613e674a94aea3a5abd50044f9",
            "input": "Intracellular targets sensitive to oxidized damage generated by photodynamic therapy (PDT) utilizing N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-mesochlorin e6 monoethylenediamine (Mce6) conjugates was explored to aid in the design of second generation PDT delivery systems.', 'Low temperature, metabolic inhibitor, and nuclear localization sequences (NLS(FITC)) were used to achieve desired subcellular localization that was evaluated by confocal analysis and subcellular fractionation. Mce6 was bound to HPMA copolymer conjugates via non-degradable dipeptide linkers (P-GG-Mce6, P-NLS(FITC)-GG-Mce6) or lysosomally degradable tetrapeptide spacers (P-GFLG-Mce6, P-NLS(FITC)-GFLG-Mce6). Chemotherapeutic efficacy was assessed by the concentration that inhibited growth by 50% (IC50), cell associated drug concentration (CAD) and confocal microscopy.', 'P-GFLG-Mce6 possessed enhanced chemotherapeutic activ ity compared to P-GG-Mce6 indicating enzymatically released Mce6 was more active than copolymer-bound Mce6. Lysosomes appeared less sensitive to photodamage as observed by a higher IC50. Nuclear-directed HPMA copolymer-Mce6 conjugates (P-NLS(FITC)-GG-Mce6, P-NLS(FITC)-GFLG-Mce6) possessed enhanced chemotherapeutic activity. However, control cationic HPMA copolymer-Mce6 conjugates containing a scrambled NLS (P-scNLS(FITC)-GG-Mce6) or amino groups (P-NH2-GG-Mce6) also displayed increased chemotherapeutic activity.",
            "output": [
                "Does correlation of subcellular compartmentalization of HPMA copolymer-Mce6 conjugate with chemotherapeutic activity in human ovarian carcinoma cells?"
            ]
        },
        {
            "id": "task847-f2b3689c1b084a5f8cfb4c3be15ce302",
            "input": "Gut ischemia/reperfusion (I/R) frequently occurs in clinical settings as a result of disproportionate splanchnic hypoperfusion during shock. Glutamine (GLN) supplementation of total parenteral nutrition (TPN) before gut I/R improves survival after gut I/R compared with standard TPN. However, it is unknown whether GLN treatment after the occurrence of the insult is beneficial or not. The aims of this study were to examine effects of GLN infusion during gut ischemia on survival, myeloid cell (neutrophils + monocytes) activation, and vascular permeability in organs.', 'Male Institute of Cancer Research (ICR) mice were randomized to control and GLN groups. After IV cannulation, mice underwent 90 (experiments 1 and 2) or 60 (experiment 3) minutes of gut I/R. Control mice received normal saline infusion at 1 mL/h for 60 minutes during ischemia, whereas the GLN group was given 3% GLN solution. In experiment 1, survival rates were monitored for 72 hours (n = 25). In experiment 2, peripheral blood was obtained at 2 or 4 hours after reperfusion (n = 17). Reactive oxygen intermediate (ROI) production by myeloid cells was determined by flow cytometry using dihydrorhodamine 123 with or without phorbol myristate acetate stimulation. Expression of CD11a and CD11b on myeloid cells was also measured. Myeloperoxidase (MPO) activity in the lung was evaluated. In experiment 3, vascular permeability in organs was measured using Evans blue at 2 or 4 hours.', 'In experiment 1, survival time in the GLN group was significantly reduced compared with the control group (p = .02, log-rank test). The survival rates were 92% (12/13) and 42% (5/12) for the control and GLN groups at 12 hours (p = .01) and 38% (5/13) and 0% (0/12) at 48 hours (p = .02), respectively. In experiment 2, ROI production was significantly higher in the GLN group than in the control group after PMA stimulation both at 2 and 4 hours. CD11b expression was significantly higher in the GLN group than in the control group at 4 hours. There was no difference in pulmonary MPO activity at either time point. In experiment 3, GLN infusion significantly increased hepatic vascular permeability compared with saline infusion at 4 hours.",
            "output": [
                "Is glutamine infusion during ischemia detrimental in a murine gut ischemia/reperfusion model?"
            ]
        },
        {
            "id": "task847-6d8f6a121fdb4a8db8648f0b65a9fabf",
            "input": "In the isolated perfused pancreas, gastric inhibitory polypeptide (GIP) has been shown to enhance glucagon secretion at basal glucose concentrations, but in healthy humans no glucagonotropic effect of GIP has yet been reported. Therefore, we studied the effect of GIP on glucagon secretion under normoglycaemic conditions.', \"Ten healthy subjects (9 men, 1 woman; age 33+/-11; BMI 26.8+/-2.2 kg/m(2)) received three different doses of intravenous GIP (7, 20, and 60 pmol/kg body weight) and placebo. Venous blood samples were drawn over 30 min for glucagon and GIP concentrations (specific radioimmunoassays). In addition, 31 healthy subjects (16 men, 15 women; 42+/-11 years; BMI 24.4+/-2.7 kg/m(2)) were studied with 20 pmol GIP/kg. Statistics were done with RM-ANOVA and Duncan's post hoc tests.\", 'Gastric inhibitory polypeptide dose-dependently stimulated glucagon secretion ( p=0.019) with a maximal increment after 10 min. Incremental glucagon concentrations (Delta(10-0 min)) were 0.1+/-0.7, 1.4+/-0.5, 2.4+/-0.5, and 3.4+/-0.8 pmol/l (for placebo and for 7, 20, and 60 pmol GIP/kg, respectively; p=0.017). After the injection of 20 pmol GIP/kg b.w. in 31 healthy subjects, glucagon concentrations increased over the baseline from 7.5+/-0.5 to 9.3+/-0.7 pmol/l ( p=0.0082).",
            "output": [
                "Does gastric inhibitory polypeptide ( GIP ) dose-dependently stimulate glucagon secretion in healthy human subjects at euglycaemia?"
            ]
        },
        {
            "id": "task847-1677040bb3ae41b0ba5b7671d0037d03",
            "input": "To measure the clearance intraperitoneal mitomycin C and doxorubicin in patients having peritonectomy and analyze the impact of the extent of peritoneal resection on pharmacokinetics.', 'A group of 15 patients with peritoneal carcinomatosis were submitted to cytoreductive surgery and heated intraperitoneal chemotherapy. Ten patients received mitomycin C and five, doxorubicin. Six patients underwent total parietal peritonectomy and nine had less-extensive peritonectomy. Pharmacokinetics were determined by sampling peritoneal fluid and blood. Drug concentrations over time, area under the curve ratios and the amount of drug recovered from the peritoneal cavity were calculated and compared between the groups.', 'The concentrations of mitomycin C over time in the peritoneal fluid and plasma were similar in five patients with total parietal peritonectomy as compared to five patients with less-extensive peritonectomy ( P=0.5350 and 0.6991; Mann-Whitney test). Mitomycin C area under the curve ratio in total peritonectomy patients was 20.5 and 25.7 in patients with less-extensive peritonectomy. The difference in total amount of drug recovered from the peritoneal cavity was not significant (30.6+/-6.188% versus 22.6+/-3.84%, P=0.095). In the studies with doxorubicin, one patient underwent total parietal peritonectomy with similar pharmacokinetics to four patients submitted to partial peritonectomy.",
            "output": [
                "Does extent of parietal peritonectomy change intraperitoneal chemotherapy pharmacokinetics?"
            ]
        },
        {
            "id": "task847-ed4593b3c2f64a24aee8ece121aa2600",
            "input": "To establish a novel approach for quick and high throughput verification of human gene imprinting.', \"By use of a pair of dye-labeled probes, 5' nuclease assay was combined with reverse transcriptase-PCR(RT-PCR) to genotype a coding single nucleotide polymorphism (cSNP), rs705(C/T) of a known imprinted gene, small nuclear ribonucleotide protein N (SNRPN), on both genomic DNA and cDNA of human lymphoblast cell lines.\", 'Allele discrimination showed a clear monoallelic expression pattern of SNRPN, which was confirmed by RT-PCR based restriction fragment length polymorphisms. Pedigree analysis verified the paternal origin of expressed allele, which is in consistency with previous report.",
            "output": [
                "Is [ Coding single nucleotide polymorphism an ideal marker for detecting gene imprinting by 5 ' nuclease assay ]?"
            ]
        },
        {
            "id": "task847-f2d3b7fac89d44cebcf74111db64e768",
            "input": "Factors related to malignant transformation of laryngeal precancerous lesions remain largely unknown, so we investigated the relationship between the expression of p27 and precancerous laryngeal lesion.', 'In this study we investigated the expressions of p27 and p53 protein in 56 cases with laryngeal precancerous or cancer lesions (20 cases of hyperplasia, 19 of dysplasia, and 17 of squamous cell carcinoma), and went on to evaluate the relationship between immunoreactivity of each of them and the histological findings. We also evaluated the correlation between immunoreactivity and proliferative activity with the aid of Ki-67 nuclear antigen staining.', 'A retrospective study was performed in 56 cases (20 with epithelial hyperplasia, 19 with epithelial dysplasia and 17 with laryngeal cancer). Immunohistochemistry was performed to investigate expression of p27, p53 protein and Ki-67 nuclear antigen staining, using the avidian-biotin-peroxidase complex technique.', 'p27 immunostaining was observed in 12 out of 20 cases of hyperplasia (60%), six out of 19 cases of dysplasia (31%), and 2/17 (12%) of carcinoma. We found significant association between p27 immunostaining and the histological findings. On the other hand, p53 immunostaining was observed in 6/20 (30%) of hyperplasia, 3/19 (16%) of dysplasia, and 7/17 (41%) of carcinoma. No significant association was found between p53 and the histological findings.",
            "output": [
                "Is reduced expression of p27 correlated with progression in precancerous lesions of the larynx?"
            ]
        },
        {
            "id": "task847-aabf47935e46414a8de13f08ad0c71d0",
            "input": "Neurotrophins elicited short-term glutamate release from the presynaptic locus. The aim of this study was to investigate short-term effects of neurotrophin-3 (NT-3) on the membrane current of inner hair cells (IHCs).', 'IHCs were isolated from the guinea-pig cochlea. Membrane currents were measured by conventional whole-cell voltage-clamp recordings. NT-3 was dissolved in a standard external solution and applied to the IHCs under pressure using pipettes.', 'Six out of eight IHCs demonstrated a suppression of K currents by extracellular application of NT-3. At +60 mV, the amplitudes of the outward current in the control and NT-3 solutions were 5.6+/-1.3 and 4.2+/-1.0 nA, respectively. NT-3 suppression was voltage-independent. One cell showed an immediate suppression with NT-3 and the following potentiation during washing with standard saline.",
            "output": [
                "Does neurotrophin-3 modify potassium currents in isolated inner hair cells from guinea-pig cochlea?"
            ]
        },
        {
            "id": "task847-a79c6000ed5c42b3b6a73a3bfb61e649",
            "input": "The NOTCH4 gene has a promoter polymor-phism at position -25, which leads to the three genotypes TT, CT and CC. These have been suggested to present a novel independent genetic risk factor for schizophrenia. We conducted a prospective case-control study to explore the impact of NOTCH4 T-25C polymorphism on the factors associated with schizophrenia.', 'NOTCH4 gene promoter T-25C polymorphism was determined by polymerase chain reaction among 94 patients with schizophrenia and 94 healthy age-matched and sex-matched blood donors.', 'The T allele was highly associated with an earlier age of onset in male patients of schizophrenia (Kaplan-Meier log-rank test P<0.0001). Moreover, the male patients carrying the T allele were born significantly more often in June-November compared with other months of the year [odds ratio=3.92 (95% confidence interval=1.025-15.018), P=0.046]. No association was determined, however, between the NOTCH4 gene polymorphism under study and schizophrenia.",
            "output": [
                "Is nOTCH4 gene promoter polymorphism associated with the age of onset in schizophrenia?"
            ]
        },
        {
            "id": "task847-f8602cabddee460c89018097a6bb98a8",
            "input": "The Achilles tendon is one of the most common sites of tendon injury and rupture. One of the early events of wound healing is angiogenesis, in which neovascularization prompts delivery of inflammatory cells and fibroblasts to the wound site. Angiogenesis is controlled by a variety of mitogenic, chemotactic, or inhibitory peptides and lipid factors that act on invading endothelial and smooth muscle cells. One of the most important angiogenic factors is the vascular endothelial cell growth factor (VEGF), a glycosylated protein of 46-48 kDa composed of two disulfide-linked subunits.', 'We therefore investigated the expression of VEGF during healing of artificial lesions of the Achilles tendon in a sheep model by immunohistochemical, biochemical, molecular, and cell biology methods. Two groups were created, the Achilles tendon was tenotomized, and the animals were killed at 3 and 24 weeks. Each group consisted of 6 specimens. Six animals which did not undergo surgery served as controls.', 'VEGF could be immunostained in tenocytes of ruptured but not in normal adult tendons. At microvessels, the receptors VEGFR-1 (flt-1) and VEGFR-2 (KDR) could also be visualized. High VEGF levels in ruptured and negligible levels in normal Achilles tendons could be confirmed and quantified by enzyme-linked immunoassay (ELISA). The highest VEGF concentrations were found in ruptured tendons, whereas the VEGF content in healthy adult tendons was negligible. Interestingly, the VEGF concentration of the original tendon stump was higher after 3 weeks than that of the newly regenerated tendon tissue. However, this difference was not significant (p>0.05). Reverse transcription-polymerase chain reaction (RT-PCR) showed that the splice variants VEGF(120 )and VEGF(164) are expressed at 3 weeks and 24 weeks, respectively.",
            "output": [
                "Are the splice variants 120 and 164 of the angiogenic peptide vascular endothelial cell growth factor ( VEGF ) expressed during Achilles tendon healing?"
            ]
        },
        {
            "id": "task847-67ff1991c5eb4d0ca032fa633b88740d",
            "input": "Parathyroidectomy (PTx) is the most successful treatment for advanced secondary hyperparathyroidism (2HPT) not responsive to medical treatment. However, persistent HPT remains problematic after PTx if some glands remain. The clinical course in patients with persistent 2HPT was evaluated to clarify the risk for re-operation after PTx.', 'Between March 1981 and December 2001, initial total PTx with forearm autograft were performed in 1156 uraemic patients. Persistent HPT cases were defined as those in which the lowest post-operative intact parathyroid hormone (i-PTH) concentration was >60 pg/ml, and patients were classified into groups A, B and C, with i-PTH concentrations of >or=500, 300-500 and 60-300 pg/ml, respectively. These patients were followed for 7-234 months after PTx.', 'Persistent HPT was identified in 49/1156 patients (4.2%), with nine cases in group A, 10 in group B and 30 in group C. Re-operation was required in 21/49 (42.8%) cases, and in seven of these the last i-PTH concentration was >or=500 pg/ml. All cases in group A required re-operation. In group C, 11/30 (36.7%) patients required re-operation. The missed glands removed at re-operation were supernumerary in 14 cases, and located in the mediastinum in 13 cases. The frequency of advanced HPT and re-operation was not negligible.",
            "output": [
                "Is re-operation frequently required when parathyroid glands remain after initial parathyroidectomy for advanced secondary hyperparathyroidism in uraemic patients?"
            ]
        },
        {
            "id": "task847-c9868018c3a14d528ce14cb7b0bd3ae0",
            "input": "The aim of this study was to examine the efficacy and safety of a new digitized, controlled, scalp-cooling system to prevent chemotherapy-induced alopecia.', \"Seventy-four female cancer patients who received 13 varying chemotherapy regimens were included in a nonrandomized pilot study. The Digni 2-3 with Dignicap system consists of a refrigerator unit and a control unit integrated into a mobile cabinet and connected to a tight-fitting cooling cap. This system maintains a constant scalp temperature of +5 degrees C for many hours. In this study, 60 patients were treated for ovarian cancer with either taxane or epirubicin combination chemotherapy. Eight patients with Hodgkin's lymphoma, three with breast cancer, two with endometrial cancer, and one with sarcoma were also included. Photo documentation and patient assessment of hair loss and discomfort were performed.\", 'In anthracycline-treated patients, total prevention of hair loss was observed, whereas hair loss in paclitaxel/docetaxel-treated patients was minimal to none. The combination of anthracycline and taxane resulted in more hair loss, but only three of six patients used a wig. Scalp cooling was generally very well tolerated; only two of 74 patients discontinued use of the cold cap due to discomfort. No scalp metastases occurred over a median follow-up period of 15 months.",
            "output": [
                "Is scalp hypothermia to prevent chemotherapy-induced alopecia effective and safe : a pilot study of a new digitized scalp-cooling system used in 74 patients?"
            ]
        },
        {
            "id": "task847-fd0f911d5b624c81a28d5c59c691bcf5",
            "input": "After formation of the linear heart tube a chamber-specific program of gene expression becomes active that underlies the formation of the chamber myocardium. To assess whether this program is recapitulated in in vitro differentiated embryonic stem cells, we performed qualitative and quantitative analyses of cardiogenesis in vivo and in vitro.', 'Gene expression profiles were made by in situ hybridisation and real-time PCR and electrophysiological profiles by patch clamp analyses of cardiomyocytes derived from time series of differentiating HM1 mouse embryonic stem cells and from embryonic and adult mouse hearts.', 'In embryoid bodies the in situ patterns of expression of alpha-myosin heavy chain, myosin light chain 2a and sarcoendoplasmic reticulum calcium ATPase 2a were similar to that of the heart muscle-specific marker gene cardiac troponin I. Myosin light chain 2v was expressed in part of the cardiac troponin I-expressing area, indicating heterogeneity within the cardiac cell population. Atrial natriuretic factor expression, indicative of the chamber-type program, could only very occasionally be detected by in situ hybridisation. Quantitative reverse transcriptase PCR showed that all cardiac genes, most notably atrial natriuretic factor, were expressed at relatively low levels, similar to those in embryonic hearts at embryonic day 8.75-9. Analysis of the electrophysiological characteristics of embryonic stem cell-derived cardiomyocytes showed an increase of the upstroke velocity and a shorter duration of the action potential during prolonged differentiation in vitro. When embryonic mouse heart compartments of embryonic day 12.5 were used as a reference, the electrophysiological characteristics of a substantial part of the embryonic stem cell-derived cardiomyocytes were most reminiscent to those observed in the embryonic outflow tract.",
            "output": [
                "Do cardiomyocytes derived from embryonic stem cells resemble cardiomyocytes of the embryonic heart tube?"
            ]
        },
        {
            "id": "task847-d4fc2506eb3c49db995fb42daa106891",
            "input": "Endoscopic surveillance for adenocarcinoma in patients with Barrett's esophagus is costly, with one cancer detected every 48-441 patient years of follow up. Genetic abnormalities, including loss of heterozygosity at sites of tumor suppressor genes, have been detected in malignant and premalignant Barrett's esophagus. The aim of this prospective study was to determine if loss of heterozygosity analysis could identify patients with Barrett's esophagus at greatest risk of adenocarcinoma, for whom endoscopic surveillance is most appropriate.\", \"Loss of heterozygosity analysis was performed on endoscopic biopsies from 48 patients as part of a Barrett's surveillance program using 14 microsatellite markers shown previously to detect loss of heterozygosity in more than 30% of esophageal adenocarcinomas. Patients were followed up endoscopically for a median of 5 years.\", 'Loss of heterozygosity was detected in nine patients. Three patients with loss of heterozygosity on chromosome 5q or 9p did not progress beyond metaplasia. Loss of heterozygosity at 17p11.1-p13 was detected in six patients, all of whom demonstrated dysplasia and/or carcinoma during follow up (four low-grade dysplasia, one high-grade dysplasia and one adenocarcinoma).",
            "output": [
                "Does loss of heterozygosity on chromosome 17p predict neoplastic progression in Barrett 's esophagus?"
            ]
        },
        {
            "id": "task847-3513c6a19ecb40278250e39e2c44656d",
            "input": "Eradication of Helicobacter pylori is not routinely recommended for the symptomatic relief and the prevention of gastric cancer in patients with functional dyspepsia. The present study investigated a useful indicator of H. pylori eradication in such patients by determining the optimal cutoff value of a 13C-urea breath test (UBT).', 'One hundred dyspeptic patients participated in the study. Dyspepsia was scored, and a 13C-UBT administered. A level of delta 13C-UBT of>4 per thousand was diagnosed as H. pylori-positive. After the stomach was endoscopically sprayed with phenol red, biopsy specimens were taken from the antrum, body and cardia of the stomach for the assessment of H. pylori density, and activity (neutrophil infiltration) and degree (lymphocyte infiltration) of gastritis.', 'Correlation between delta 13C-UBT and dyspepsia score was not found. Delta 13C-UBT significantly correlated with H. pylori density score in the total stomach (r = 0.53, P < 0.0001), neutrophil (r = 0.34, P = 0.0005) and lymphocyte score (r = 0.69, P < 0.0001). Twenty-six of the 100 subjects had a neutrophil score of >or=4, lymphocyte score of >or=4, and H. pylori score of >or=4. Their 95% confidence interval of mean was 58.2 per thousand, which reflects moderate to marked acute and chronic gastritis, and dense H. pylori colonization.",
            "output": [
                "Is delta ( 13 ) C-urea breath test value a useful indicator for Helicobacter pylori eradication in patients with functional dyspepsia?"
            ]
        },
        {
            "id": "task847-b4612c04717d4877a6a085a0c17ae365",
            "input": "Not all alcoholic patients develop severe liver disease with fibrosis progressing to cirrhosis. It is of practical importance to determine whether some markers can predict progression of liver fibrosis.', 'We used a baboon model that mimics human alcoholic liver disease. Cytokeratin 7 and 19 expression and fat deposition were investigated in serial liver biopsies of 18 animals undergoing prolonged alcohol administration (range 2-17 years) and in four controls. Fibrosis was graded histologically and was also assessed quantitatively by image analysis.', 'Ten animals did not show a progression of liver disease even after 17 years of alcohol administration, but eight animals fed alcohol exhibited a progression of liver disease from no fibrosis or perivenular fibrosis to septal fibrosis or cirrhosis within 7 years. In normal liver, cytokeratin 7 and cytokeratin 19 immunostaining is restricted to bile duct cells. Hepatocellular cytokeratin 7 was observed only in those animals which progressed to more severe stages of fibrosis and it anticipated this progression by 4.2 years on average.",
            "output": [
                "Does cytokeratin 7 staining of hepatocytes predict progression to more severe fibrosis in alcohol-fed baboons?"
            ]
        },
        {
            "id": "task847-c78d571df1184451836ac48257881e65",
            "input": "Insulin- and insulin growth factor-1 stimulated signaling through the insulin receptor substrate-1 (IRS-1) promotes hepatocellular proliferation and survival. IRS-1 over-expression in transgenic (Tg) mouse livers caused constitutive activation of Erk mitogen activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) resulting in significantly increased levels of DNA synthesis and larger hepatic masses relative to non-transgenic (non-Tg) littermates. However, the livers eventually ceased to grow but remained approximately 25% larger than non-Tg livers. We hypothesized that this growth homeostasis was achieved by parallel activation of pro-apoptosis pathways.', 'Since Fas-mediated apoptosis is a common mechanism of hepatocyte destruction, we investigated the potential role of Fas receptor as a regulator of hepatic mass in IRS-1 transgenic mice.', 'Significantly increased Fas-receptor levels were detected in the livers of IRS-1 Tg compared to non-Tg mice by Western blot analysis. Functional activation of Fas-receptor in IRS-1 Tg livers was demonstrated by increased hepatocellular apoptosis caused by intravenous injection of anti-Fas (Jo-2).",
            "output": [
                "Does constitutive over-expression of the insulin receptor substrate-1 cause functional up-regulation of Fas receptor?"
            ]
        },
        {
            "id": "task847-23bf94e5bc9a4bfbaa25231760f82a22",
            "input": "For patients with small bowel obstruction (SBO), who do not have strangulation obstruction or other contraindications, long tube decompression has been successful in 75% in two studies. In a 1995 prospective randomized study, comparing nasogastric suction (short tube) with long tube decompression, the short tube was successful in 51% and the long tube was successful in 75%. Using upper gastrointestinal endoscopy, a long tube can be advanced into the jejunum in 20 minutes, so the delay in function has been eliminated.', 'There were 35 patients with 37 episodes of SBO. From 1983 to 1988, three tubes then available were advanced endoscopically into the jejunum in 17 patients. From 1989 to 2002, an improved tube designed for endoscopic placement was used in 20 patients.', 'From 1983 to 1988 using three tubes, long tube decompression was successful in 12 of 17 (70%); from 1989 to 2002 with the improved tube, decompression was successful in 18 of 20 (90%).",
            "output": [
                "Is long tube decompression successful in 90 % of patients with adhesive small bowel obstruction?"
            ]
        },
        {
            "id": "task847-fe87110dc21641818eefafd4360dea9b",
            "input": "In previous studies, pyridoxamine (PM) limited the formation of advanced glycation end products (AGEs) and development of nephropathy in streptozotocin-diabetic rats without affecting glycemic control. However, the lipid-lowering effects of PM and the correlation of plasma cholesterol and triglycerides with AGEs in skin collagen suggested that lipids might be an important source of AGEs in the diabetic rat. This study addresses the effects of hyperlipidemia on formation of advanced glycation and lipoxidation end products (AGE/ALEs) and the effects of PM on hyperlipidemia, hypertension, AGE/ALE formation, and development of nephropathy in the nondiabetic, Zucker obese rat.', 'Three groups of Zucker rats were studied: lean (Fa/fa), untreated fatty (fa/fa), and fa/fa treated with PM (2 g/L drinking water). Blood pressure, plasma lipids and creatinine, and urinary albumin were measured monthly. AGE/ALEs were measured in skin collagen by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Changes in wall thickness of the aorta and renal arterioles were evaluated by light microscopy.', 'AGE/ALEs formation was increased two- to threefold in skin collagen of obese versus lean rats. PM inhibited the increases in AGE/ALEs in collagen, and significantly decreased the rise in plasma triglycerides, cholesterol, and creatinine, corrected hypertension and thickening of the vascular wall, and nearly normalized urinary protein and albumin excretion in Zucker fa/fa rats.",
            "output": [
                "Does the AGE inhibitor pyridoxamine inhibit lipemia and development of renal and vascular disease in Zucker obese rats?"
            ]
        },
        {
            "id": "task847-f94841c699cc45c68e1a7217b0f06620",
            "input": "To observe pharmacological difference between ultra-fine particles of six ingredient Rehmannia pill and traditional six ingredient Rehmannia pill.', 'Pharmacokinetic index was measured by death rate, and pharmacology actions were compared by anti-fatigue, hypoglycemic, clearance rate of charcoal particle, hypoxia resistance and serum hemolysin concentration experiment.', 'Dose-effection was significant and pharmacology actions were more than traditional six ingredient Rehmannia pill in six ingredient Rehmannia pill.",
            "output": [
                "Do [ Study on pharmacology of ultra-fine particles compound Rehmannia ]?"
            ]
        },
        {
            "id": "task847-a88689a66edf450190cf505857e692a7",
            "input": "Corticosteroids remain the mainstay for control of ocular inflammation after vitreous surgery. A controlled, randomized, prospective study was performed to evaluate the effectiveness of a single intravitreal injection of dexamethasone phosphate on postoperative inflammation after simple vitreous surgery in patients with proliferative diabetic retinopathy and macular pucker.', 'Aqueous cell flare intensity was measured preoperatively and on days 1, 10, and 90 in 56 consecutive patients who underwent vitreous surgery for proliferative diabetic retinopathy and macular pucker. Subjects were consecutively randomized to two groups: 400 microg of intravitreal dexamethasone (treatment group) or no dexamethasone (control group)', 'Before surgery, cell and flare intensity was similar in both groups. Flare intensity was significandy lower at 10, 30, and 90 days in the proliferative diabetic retinopathy treatment group (P < .05).",
            "output": [
                "Does intravitreal dexamethasone effectively reduce postoperative inflammation after vitreoretinal surgery?"
            ]
        },
        {
            "id": "task847-8492d36d25954b94ac88a24effd01e6a",
            "input": "Role of mast cells in the development of allergen-induced airway remodelling has not been fully investigated in vivo.', 'To clarify the possible role of mast cells in the development of allergen-induced airway remodelling, we compared their responses of genetically mast cell-deficient mice, WBB6F1-W/Wv (c-kit mutant) and Sl/Sld (c-kit ligand mutant) mice with those of congenic normal mice in a murine model of allergic asthma.', 'Mice were sensitized to ovalbumin (OA) with alum, and exposed daily for 3 weeks to aerosolized OA. Twenty-four hours after the last inhalation, bronchial responsiveness to acetylcholine (Ach) was measured, and bronchoalveolar lavage (BAL), and biochemical and histological examinations were performed.', 'In both sensitized mast cell-deficient mice, the degree of bronchial hyper-responsiveness to Ach, the number of inflammatory cells and the level of transforming growth factor-beta1 in BAL fluid, IgE response and goblet cell hyperplasia in the epithelium after repeated allergen provocation were not significantly different from those of congenic mice. In contrast, subepithelial fibrosis, evaluated in the fibrotic area around the airways, observed in congenic mice after repeated allergen challenge was partially attenuated in both mast cell-deficient mice. In addition, the amount of hydroxyproline in the lung of mast cell-deficient mice was significantly lower than that of congenic mice. Furthermore, the decreased fibrotic area and amount of hydroxyproline in W/Wv mice was completely recovered by reconstitution of tissue mast cells with bone marrow-derived mast cells of congenic mice.",
            "output": [
                "Do mast cells play a partial role in allergen-induced subepithelial fibrosis in a murine model of allergic asthma?"
            ]
        },
        {
            "id": "task847-96a271d0b3d445acaaf11b4441db35fd",
            "input": "The functional recovery of the remnant liver after an extended hepatectomy is critical for the outcome of the patient. The aim of this prospective study was to examine whether biliary bile acids could be an indicator for postoperative liver function.', 'Externally drained bile samples were obtained from 51 patients with biliary or periampullary carcinomas before and after surgery. Patients were categorized into 3 groups: group A, 29 hepatectomized patients without liver failure; group B, 7 hepatectomized patients with liver failure (maximum serum bilirubin level, >10 mg/dL); and group C, 15 patients who underwent biliopancreatic resection without hepatectomy, with a good postoperative course. Bile samples were withdrawn 1 day before surgery and on postoperative days 1, 2, 3, 4, 6, and 7. Total bile acids were measured with a 3 alpha-hydroxysteroid dehydrogenase method.', 'Before surgery, the concentration of bile acids was higher in groups A and C than in group B, and correlated significantly with the indocyamine green disappearance rate (KICG) values (R(2) = 0.557; P <.0001). After surgery, bile acid concentrations decreased in all 3 groups until postoperative day 2, which was followed by a gradual increase. The concentration recovered to the preoperative level in groups A and C but remained low in group B. Biliary bile acid concentrations on day 2 correlated significantly with remnant liver KICG values (R(2) = 0.257; P =.0019). Among several parameters studied, including KICG, remnant liver KICG, biliary bile acids, and biliary bilirubin, biliary bile acid concentration had the most predictive power for occurrence of postoperative liver failure.",
            "output": [
                "Is biliary bile acid concentration a simple and reliable indicator for liver function after hepatobiliary resection for biliary cancer?"
            ]
        },
        {
            "id": "task847-5a8896b296194ebc9ef94c717d39b064",
            "input": "The purpose of this study was to determine whether periodontal disease is associated with endothelial dysfunction and systemic inflammation. Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown.', 'We assessed flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery using vascular ultrasound in 26 subjects with advanced periodontal disease and 29 control subjects. The groups were matched for age and sex, and patients with hypercholesterolemia, diabetes mellitus, hypertension, and history of cigarette smoking were excluded. We also examined serum levels of C-reactive protein using an established high-sensitivity method. Subjects with advanced periodontal disease had lower flow-mediated dilation compared with control patients (7.8+/-4.6% versus 11.7+/-5.3%, P=0.005). Nitroglycerin-mediated dilation was equivalent in the two groups. Subjects with advanced periodontitis exhibited higher serum levels of high-sensitivity C-reactive protein compared with healthy controls patients (2.3+/-2.3 versus 1.0+/-1.0 mg/L, P=0.03).",
            "output": [
                "Is periodontal disease associated with brachial artery endothelial dysfunction and systemic inflammation?"
            ]
        },
        {
            "id": "task847-a645ec9e74e94096899881feb7c9168d",
            "input": "The migratory capability of vascular endothelial cells plays a pivotal role in the maintenance of vessel wall integrity and is stimulated by nitric oxide (NO). Angiotensin II increases NAD(P)H oxidase activity in endothelial cells, thereby promoting reactive oxygen species (ROS) generation. Because ROS can both reduce NO synthase activity and increase NO breakdown, thus impairing NO availability in endothelial cells, we evaluated the effect of angiotensin II on human vascular endothelial cell (HUVEC) motility.', 'Angiotensin II dose- and time-dependently reduced HUVEC migration. Besides inhibiting HUVEC motility, angiotensin II altered intracellular glutathione redox status. The generation of ROS by cultured HUVECs was significantly increased by angiotensin II. Furthermore, angiotensin II reduced NO metabolite concentrations in culture media. The angiotensin II type 1 receptor antagonist candesartan cilexetil attenuated the inhibitory action exerted by angiotensin II on HUVEC motility, reversed the angiotensin II-induced increase in intracellular oxidative stress, and restored NO availability. Similar effects were exerted by the flavonoid inhibitor diphenylene iodinium and the antioxidant agent N-acetyl-L-cysteine.",
            "output": [
                "Does angiotensin II inhibit endothelial cell motility through an AT1-dependent oxidant-sensitive decrement of nitric oxide availability?"
            ]
        },
        {
            "id": "task847-c923d22c76354c598c54b34a4ee5365e",
            "input": "Closed suction drains have an important role in surgical wound healing. Although most surgeons use them routinely, indications for use and their postoperative management (emptying, removal) vary. The purpose of this study was to assess drain use by head and neck surgeons in Canada, to conduct a biomechanical analysis of the drains in a laboratory setting, and to make recommendations for drain use and management.', 'A survey was mailed to 343 active members of the Canadian Society of Otolaryngology. Three sets of experimental trials were conducted on the most commonly used drains to assess the effect of increased reservoir filling on suction generated through (1) incrementally increasing the amount of fluid within the reservoir, (2) compression of the reservoir with no fluid within, and (3) compression with the reservoirs while filled to 25% capacity with fluid.', 'A 41% response rate was obtained. It was found that the majority of head and neck surgeons in Canada use Hemovac and Jackson-Pratt drainage systems routinely. There is considerable variability in practice with regard to drain emptying and timing of removal. Experimental results indicate that as filling of the reservoir increases, suction generated decreases sharply, to between 13 and 20% of initial values at 50% capacity.",
            "output": [
                "Does survey of the use of suction drain in head and neck surgery and analysis of their biomechanical properties?"
            ]
        },
        {
            "id": "task847-8e6e5aac5c0342878d7062e017d35468",
            "input": "After head injury, impaired cerebrovascular autoregulation has been associated with abnormally high or low cerebral blood flow. The physiological relevance of cerebral blood flow levels is difficult to assess in these patients, whose cerebral metabolic rate for oxygen (CMRO(2)) is known to be abnormal. Investigation of these relations requires quantitative measures of cerebral blood flow and CMRO(2), to allow assessment of oxygen supply and demand relations.', 'To investigate the relation between dysautoregulation and global cerebral oxygen metabolism following head injury.', 'Using positron emission tomography, global cerebral blood flow, CMRO(2), and oxygen extraction fraction were determined in 22 patients who were investigated in 26 examinations on days 1 to 11 (mean (SD), 3.5 (2.3)) after head injury. Cerebrovascular pressure reactivity was assessed using a pressure reactivity index, calculated as the moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure. Outcome was assessed six months after injury using the Glasgow outcome scale.', 'Low CMRO(2) was associated with disturbed pressure reactivity (inverse function, R(2) = 0.21, p = 0.018) and there was a correlation between disturbed pressure reactivity and oxygen extraction fraction (quadratic function, R(2) = 0.55, p = 0.0001). There was no significant relation between pressure reactivity and cerebral blood flow. An unfavourable outcome was associated with disturbed pressure reactivity. There was no significant relation between outcome and CMRO(2) or oxygen extraction fraction.",
            "output": [
                "Is cerebrovascular pressure reactivity related to global cerebral oxygen metabolism after head injury?"
            ]
        },
        {
            "id": "task847-936f09bbaf3d479cb46ebf24fed907d8",
            "input": "So far the issue of patch tests with mite allergens in subjects not affected by atopic dermatitis (AD) has been poorly investigated. The aim of this study was to assess the frequency and intensity of responses to atopy patch tests with Dermatophagoides in non-AD subjects, and to compare them to the ones observed in AD patients.', 'Patch tests were performed, employing a mixture of Dermatophagoides pteronyssinus and farinae at two different concentrations (20 and 40% pet.), on 75 non-AD subjects, including 33 patients with allergic rhinitis and 42 healthy volunteers, and on 210 AD patients, as controls.', 'Positive responses to 20% mite patch tests were observed in 17 non-AD subjects (23%) and in 102 AD ones (49%). The former showed a lower intensity of the responses, with a mean score of 1.4 compared with 2.1 in atopics.",
            "output": [
                "Are frequency and intensity of responses to mite patch tests lower in nonatopic subjects with respect to patients with atopic dermatitis?"
            ]
        },
        {
            "id": "task847-a49bf6c8a0cb4cc38798de35028e02e4",
            "input": "Genetic abnormalities of the pituitary specific transcription factor, Pit-1, have been reported in several patients with GH, prolactin (PRL) and TSH deficiencies. The most common is a mutation altering an arginine to a tryptophan in codon 271 (R271W) in one allele of the Pit-1 gene. According to the previous in vitro expression study, R271W acted as a dominant negative inhibitor of the wild type to activate the GH promoter. However, healthy carriers with this mutation, who should be affected by the dominant negative effect of R271W, have also been reported. The aim of this study was to clarify in more detail the function of this mutant form of Pit-1.', \"Transcriptional activity of R271W for the expression of Pit-1-associated genes was investigated in COS7 cells with the aid of transient transfection assays. The 1.8 kb rat GH, 0.6 kb rat PRL or 1.9 kb rat PRL 5'-flanking regions were inserted upstream of the luciferase reporter gene and were used for functional analysis of R271W. Another reporter gene containing seven Pit-1 responsive elements was also used. The same experiments were also performed using JEG3 and CHO cells.\", 'We could not confirm the dominant negative effect of R271W on wild type Pit-1. Furthermore, our expression study revealed that R271W could activate the promoters of GH and PRL genes to levels similar to the wild type.",
            "output": [
                "Does the R271W mutant form of Pit-1 act as a dominant inhibitor of Pit-1 action to activate the promoters of GH and prolactin genes?"
            ]
        },
        {
            "id": "task847-888810490e6141aa972592950a69d9fb",
            "input": "Calcium-sensing receptor (CaR) is a candidate gene for osteoporosis susceptibility. Several CaR polymorphisms have been identified and an association between the A986S genotype and serum calcium levels has been found in Canadian postmenopausal women. We investigated whether the presence of 986S allele was associated with bone mineral density (BMD) and osteoporotic fractures.', 'The study group consisted of 164 Italian postmenopausal women without fragility fracture (Fx(-)) and 55 women with fracture (Fx(+)).', 'A fragment of exon 7 of CaR gene containing three polymorphisms (A986S, R990G and Q1011E) was amplified by PCR and sequenced. Anthropometric characteristics and BMD were evaluated.', 'The A986S polymorphism was the most commonly observed (27.9%), whereas the other two CaR polymorphisms, R990G and Q1011E, occurred in a minority of cases (8.8 and 5.5% respectively). There was no significant difference in the frequency distribution of any CaR allele between Fx(-) and Fx(+) patients. Body mass index was found to predict BMD at the lumbar spine and femoral neck. The A986S polymorphism and Years since menopause were not independent predictors of BMD at any site. As far as fracture occurrence, there was no statistically significant difference in the prevalence of fractures between women carrying or not carrying the 986S allele.",
            "output": [
                "Is calcium-sensing receptor gene polymorphism associated with bone mineral density in Italian postmenopausal women?"
            ]
        },
        {
            "id": "task847-59cb68a57ad04febb8081ba64de59bde",
            "input": "R136K is a mutation of fibroblast growth factor-1 (FGF-1) in which arginine replaces lysine at the primary thrombin cleavage site. This may be important in vivo in inducing endothelial cell (EC) migration and coverage of arterial injury sites by allowing R136K to be used in a fibrin glue delivery system, without thrombin-induced degradation, in the absence of heparin. The objectives of this study were to determine whether R136K, with and without heparin, can induce migration of EC and smooth muscle cells (SMC) through fibrin glue, and to compare these results with those of wild-type FGF-1; and to determine the resistance of R136K to thrombin-induced degradation versus FGF-1.', 'The dose-response migration through fibrin glue induced by wild-type FGF-1 and the R136K mutant in the presence and absence of heparin was tested with EC and SMC. Migration was tested with 50, 100, and 200 ng/mL of both FGF-1 and R136K, either with or without 5 U/mL of heparin. Migration of EC was also assessed after growth inhibition with mitomycin C. A novel modified Boyden chamber-type migration assay using fibrin glue on the upper surface of the chamber filter was used to test migration. The fluorescent marker calcein was used to identify those cells that had migrated through the fibrin glue and were embedded in the filter. Molecular degradation by thrombin was assessed with sodium dodecylsulfate polyacrylamide gel electrophoresis.', 'For EC, R136K in the absence of heparin induced significantly more migration than did FGF-1 at 50 (P <.002), 100 (P <.0001), and 200 (P <.0001) ng/mL. In the presence of heparin, a chemotactic response of EC to cytokine was seen at all doses, with no significant difference between FGF-1 and R136K. A dose-dependent difference was noted in this group between the 100 and 200 ng/mL concentrations of cytokine (for FGF-1, P <.0001; for R136K, P <.0001). SMC showed no difference in migration with FGF-1, R136K, or negative control at any dose in the presence or absence of heparin. Gel electrophoresis demonstrated that R136K was more resistant to thrombin degradation than was FGF-1.",
            "output": [
                "Does r136K fibroblast growth factor-1 mutant induce heparin-independent migration of endothelial cells through fibrin glue?"
            ]
        },
        {
            "id": "task847-1773a73d8bde450d860035b7d65b028d",
            "input": "Clinical evidence indicates that hemodynamic conditions influence abdominal aortic aneurysm (AAA) disease. We modified blood flow to evaluate the effects of wall shear stress (WSS) and relative wall strain (RWS) on aneurysm structure and cellularity.', 'Rodent AAAs were created with porcine pancreatic elastase infusion. In group 1 AAA WSS was increased with left femoral arteriovenous fistula creation, whereas in group 2 AAA WSS was decreased with left iliac artery ligation. Aortic flow, wall motion, and blood pressure were recorded in both groups. AAA diameter, endothelial and smooth muscle cellularity (CD31 and alpha-smooth muscle actin immunostaining), markers for cell proliferation (5-bromodeoxyuridine), endothelial and smooth muscle cell growth factor production (vascular endothelial growth factor-D and platelet-derived growth factor-beta, respectively), and apoptosis (deoxyuridine triphosphate nick end-labeled [TUNEL] stain) were compared between groups when the animals were killed.', 'Arteriovenous fistula creation increased WSS (high-flow AAA) by 300% and RWS by 150%. Iliac ligation reduced WSS (low-flow AAA) by 60%. Neither procedure significantly altered systolic, diastolic, or mean aortic pressure. When the animals were killed 7 days after elastase infusion, low-flow AAAs were significantly larger than high-flow AAAs. High-flow AAAs also contained more endothelial cells and smooth muscle cells, and evidence of increased growth factor production, cell proliferation, and decreased apoptosis. No difference in type or severity of AAA inflammatory cell infiltrate was noted between groups.",
            "output": [
                "Do wall shear stress and strain modulate experimental aneurysm cellularity?"
            ]
        },
        {
            "id": "task847-aa52921c1e864c65b63b90e1888721ef",
            "input": "The appropriateness of vigorous fluid resuscitation to normal blood pressure following hemorrhage in uncontrolled bleeding has recently been questioned due to the possibility of dislodging clots and exacerbating hemorrhage. To develop a rational blood pressure target that maximizes the metabolic benefits of resuscitation without causing increased blood loss, it was first necessary to determine whether there is a reproducible mean arterial pressure (MAP) at which rebleeding occurs. The purpose of this study was to explore the relationship between the rate and time of resuscitation after injury and the rebleeding MAP in an uncontrolled hemorrhage model.', \"Sixty-two anesthetized pigs were instrumented with catheters and splenectomized, and suction tubes were placed in the lateral peritoneal recesses to continuously capture shed blood. With the abdomen open, an aortotomy was made in the infrarenal aorta. At either 5, 15, or 30 minutes after the end of the initial hemorrhage, resuscitation with warmed lactated Ringer's solution was begun at either 100 or 300 mL/min. The rebleeding MAP was determined at the moment blood appeared in the suction tubes.\", 'The average pressure at the rebleeding point for all animals was MAP = 64 +/- 2, Systolic = 94 +/- 3, and Diastolic = 45 +/- 2 mm Hg. The pressure at which rebleeding occurred in this aortotomy model was not affected by either time of resuscitation (5-30 min), nor was the rebleeding pressure affected by the rate (100 vs. 300 mL/min) of resuscitation.",
            "output": [
                "Does blood pressure at which rebleeding occur after resuscitation in swine with aortic injury?"
            ]
        },
        {
            "id": "task847-2070d74d2d0a49c9a8441b1f66b73c2e",
            "input": "This study evaluated the prospective relationship between cardiovascular reactivity to psychological stress and increases in resting blood pressure across a 3-year period among a multiethnic pediatric sample (N = 149).', 'Systolic and diastolic blood pressure; EKG heart rate, pre-ejection period, and mean successive difference of R to R intervals; and impedance-derived measures of cardiac output, stroke volume, and total peripheral resistance were collected during performance of four tasks that elicited different hemodynamic response patterns. Changes from baseline to each task were standardized and averaged to form eight composite scores. Analyses adjusted for time 1 baseline blood pressure and age, body mass index at baseline and change to follow-up, and duration of follow-up.', 'Rises in SBP over the follow-up period were independently predicted by SBP (beta = 0.161, p =.009), DBP (beta = 0.132, p =.02), and CO (beta = 0.144, p =.02) composite measures of reactivity. Rises in DBP over the follow-up period were predicted by DBP (beta = 0.292, p =.003, respectively), and MSD (beta = -0.176, p <.03) composite measures of reactivity. TPR reactivity was not related prospectively to blood pressure rises.",
            "output": [
                "Does cardiovascular reactivity to stress predict future blood pressure in adolescence?"
            ]
        },
        {
            "id": "task847-d1bdfe073f22452eaf336912513fad9a",
            "input": "Cytogenetic aberrations are of prognostic significance in childhood acute lymphoblastic leukaemias and a high detection rate could improve the biological understanding and classification of these diseases.', 'Bone-marrow samples from 92 children with acute lymphoblastic leukaemia were studied by high-resolution comparative genomic hybridisation (HRCGH) using dynamic standard reference intervals that enhance both specificity and sensitivity in the detection of aberrations.', 'In 80 patients (87%) HRCGH revealed a total of 405 aberrations, mostly whole chromosome gains (n = 265) and partial losses (n = 80). The 25 leukaemias with a gain of more than five whole chromosomes by HRCGH harboured only 7% of all losses. With G-band karyotyping 59 patients (64%) had aberrations. HRCGH revealed more aberrations per patient than did G-band karyotyping (median: 3 vs. 1, P = 0.005), revealed aberrations in 27 of the 34 patients for whom the G-band karyotyping failed or was found to be normal, and specifically revealed more 9p losses (21% vs. 5%, P < 0.005), 12p losses (12% vs. 2%, P < 0.05) and 17q gains (11% vs. 1%, P < 0.01). Compared to the present study, the frequency of patients with aberrant karyotypes was significantly lower in previous conventional CGH studies (64% vs. 87%, P < 0.0001), as was the rate of partial aberrations per patient (1.1% vs. 1.7, P < 0.001), particularly with fewer 6q losses, 9p losses and 17q gains detected.",
            "output": [
                "Does high-resolution comparative genomic hybridisation yield a high detection rate of chromosomal aberrations in childhood acute lymphoblastic leukaemia?"
            ]
        },
        {
            "id": "task847-04262662959f484ea82ad384b88c81fe",
            "input": "Serum levels of matrix metalloproteinase-9 (MMP-9) which agree with progression in solid and haematological tumours were correlated to the risk of disease progression in 62 patients with early (Binet stage A) B-cell chronic lymphocytic leukaemia (CLL). Sera were taken at diagnosis and tested by an enzyme-linked immunosorbent assay.', 'MMP-9 levels positively correlated with haemoglobin levels (P = 0.03) and platelet count (P = 0.03). No association was found with main clinico-haematological features representative of tumour mass, such as peripheral blood lymphocytosis, bone marrow histology, Rai substages and beta-2 microglobulin (beta-2m). A cut-off of MMP-9 levels corresponding to 33rd percentile (203 ng/mL) or higher identified earlier upstaging and shorter progression-free survival. MMP-9 was a significant prognostic marker in multivariate analysis and partially independent of Rai substages, which suggests its inclusion into such a staging system to better stratify prognostically Rai stages I and II patients.",
            "output": [
                "Do increased serum levels of matrix metalloproteinase-9 predict clinical outcome of patients with early B-cell chronic lymphocytic leukaemia?"
            ]
        },
        {
            "id": "task847-44f2541baf234e098eb05dab52689bad",
            "input": "Oxidative stress and related DNA damage in human sperm may be important for fecundity and pregnancy outcome.', \"We studied the level of oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in sperm DNA among 225 first-pregnancy planners. Over the six menstrual cycle follow-up time, after cessation of contraception, 135 pregnancies were conceived.\", 'The likelihood of pregnancy occurring in a single menstrual cycle was inversely associated with the 8-oxodG level (P < 0.01). The odds ratio of pregnancy in each of the first three or all six follow-up menstrual cycles was 0.42 (0.23-0.78; 95% CI) and 0.61 (0.36-0.91) per unit increase in the log 8-oxodG/100 000 dG ratio after adjustment for potential confounders, (including sperm concentration) respectively. The intra-individual coefficient of variation of 8-oxodG in 2-6 monthly repeated sperm samples from 116 men was 19% for the 8-oxodG/dG ratio, whereas the inter-individual coefficient of variation was 49%. The 8-oxodG level was not significantly associated with smoking, consumption of alcohol or caffeine, exposure to welding fumes or the plasma levels of sex hormones.",
            "output": [
                "Does oxidative DNA damage in human sperm influence time to pregnancy?"
            ]
        },
        {
            "id": "task847-6a4aca44e18f44b0aeae9db2e8235d56",
            "input": "The etiology and pathogenesis of inflammatory bowel disease remain unknown. However, neutrophil infiltration into the inflammatory lesion is an important process in inflammatory bowel disease. In this study, we used rat trinitrobenzene sulfonic acid (TNBS) ileitis as a Crohn's disease model, and investigated the effects of oral IS-741 (which inhibits the expression of Mac-1, a cell adhesion molecule) on leukocyte-endothelial interactions.\", 'Rat ileitis was induced by the intraluminal injection of a TNBS solution (160 mg/kg in 50% ethanol) at a site 10 cm proximal to the ileocecal valve. The rats then received oral IS-741 (50 mg/kg) or saline for 7 days. On the day 8 after the initial administration of IS-741 or saline, we determined the visible damage score, and assessed myeloperoxidase (MPO) activity. Concentrations of cytokines in the ileum, such as interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were assayed by enzyme-linked immunosorbent assay (ELISA). We also investigated the infiltration of polymorphonuclear cells and Mac-1 positive cells by histological examinations.', 'The administration of IS-741 resulted in a significant reduction of the visible damage score, myeloperoxidase (MPO) activity, and mucosal IL-8 levels in the ileum as compared with the saline administration. IS-741 also dramatically reduced the infiltration of polymorphonuclear cells and Mac-1 positive cells into the inflamed lesions.",
            "output": [
                "Does a novel diamino-pyridine derivative ( IS-741 ) attenuate rat ileitis induced by trinitrobenzene sulfonic acid?"
            ]
        },
        {
            "id": "task847-7634b71bfc1744309116fd6502659a8d",
            "input": "MDMA (ecstasy; +3,4-methylenedioxymethamphetamine) damages brain serotonin (5-HT) neurons and, in non-human primates, a loss of various 5-HT axonal markers persists for several years. This raises the question of whether long lasting effects occur in human beings that persist even after they have stopped using MDMA.', 'We therefore assessed the effects of an indirect 5-HT manipulation on functions thought to be affected by MDMA use in people who had stopped using MDMA (ex-users) compared with continuing users and non-users.', 'Ninety-six participants were recruited: 32 ex-users who had stopped using MDMA for >1 year (mean, 2.4 years); 32 current users and 32 polydrug controls who had never used MDMA but were matched with ex-users and controls on cannabis use and pre-morbid IQ. Participants were given an amino acid mixture that contained either no tryptophan (T-) or augmented tryptophan (T+) and assessed before and 5 h after the drink on measures of cognitive function and mood.', \"T+ and T- produced plasma tryptophan augmentation and depletion, respectively, in all three groups. Ex-users' plasma tryptophan levels in response to T+ were significantly higher than other groups. Ex-users' performance on a delayed prose recall task improved after T+ and lessened after T-. Changes in ex-users' free plasma tryptophan levels correlated highly (r=-0.9) with their baseline performance on immediate and delayed prose recall; change in total plasma tryptophan correlated (r=-0.81) with delayed recall. Further, total baseline plasma tryptophan correlated with number of years they had used MDMA before quitting. Baseline differences between groups were found on learning, working memory, aggression and impulsivity. T- did not produce differential effects in the three groups.",
            "output": [
                "Is altered response to tryptophan supplementation after long-term abstention from MDMA ( ecstasy ) highly correlated with human memory function?"
            ]
        },
        {
            "id": "task847-d6b351c894c74a7d82faec146bcf9eff",
            "input": "Abnormal concentrations of coenzyme Q(10) have been reported in many patient groups, including certain cardiovascular, neurological, hematological, neoplastic, renal, and metabolic diseases. However, controls in these studies are often limited in number, poorly screened, and inadequately evaluated statistically. The purpose of this study is to determine the reference intervals of plasma concentrations of ubiquinone-10, ubiquinol-10, and total coenzyme Q(10) for self-reported healthy adults.', 'Adults (n=148), who were participants in the Princeton Prevalence Follow-up Study, were identified as healthy by questionnaire. Lipid profiles, ubiquinone-10, ubiquinol-10, and total coenzyme Q(10) concentrations were measured in plasma. The method used to determine the reference intervals is a procedure incorporating outlier detection followed by robust point estimates of the appropriate quantiles.', 'Significant differences between males and females were present for ubiquinol-10 and total coenzyme Q(10). Blacks had significantly higher Q(10) measures than whites in all cases except for the ubiquinol-10/total Q(10) fraction.",
            "output": [
                "Are plasma coenzyme Q10 reference intervals , but not redox status , affected by gender and race in self-reported healthy adults?"
            ]
        },
        {
            "id": "task847-0af67b8d37344b40996fff51d2721c26",
            "input": "Hematopoiesis is regulated by proliferation, differentiation, and death. p16(INK4a) has been reported to regulate apoptosis and differentiation of diverse cells, as well as arresting the cell cycle at G1 phase. The aim of this study is to explore the properties of p16 in apoptosis and differentiation of erythroid cells.', 'We transfected the INK4a gene to K562 cells, which defect the INK4a gene, and compared the effect of enforced expression of p16(INK4a) with that of various additives, topoisomerase I inhibitor (SN 38), interferon-alpha, phosphatidyl-inositol-3 kinase inhibitor (LY294002), and serum deprivation, which arrest cell cycle at different phases. We also investigated the role of p16(INK4a) in normal day-6 human erythroid colony-forming cells by transfecting the INK4a gene.', 'p16(INK4a) induced cell cycle arrest at the G0/G1 phase, and promoted erythroid differentiation in viable K562 cells, but induced apoptosis in K562 cells with incomplete differentiation. The apoptosis induced by p16 was accompanied with downregulation of bcl-x and nuclear NF-kappaB. These findings were not observed in K562 cells treated with various additives. p16(INK4a) decreased the cell viability and promoted apoptosis in day-9 ECFC.",
            "output": [
                "Does p16 ( INK4a ) induce differentiation and apoptosis in erythroid lineage cells?"
            ]
        },
        {
            "id": "task847-36a1885edce5440a897f7d19fa5ddb8a",
            "input": "Ischemia-reperfusion injury has been established as a nonimmunologic risk factor for the development of chronic graft nephropathy after renal transplantation. This objective of this study was to determine if oral administration of an endothelin-1 receptor (ET-R) antagonist over a 2-month period after renal transplantation would mitigate long-term dysfunction associated with 30 min of preretrieval warm ischemia (pre-WI).', 'The left kidney was retrieved from 250-g Lewis rats. Recipients underwent left nephrectomy and isografting using standard techniques. Animals were divided into three groups: nonischemic controls (no pre-WI, n=8); ischemic controls (pre-WI only, n=6); and pre-WI kidneys in which recipients received the ET(A/B) receptor antagonist, A182086, daily (30 mg/kg/day) (pre-WI/ET-R antagonist, n=6). Isograft glomerular filtration rate (GFR) was measured at 2 months.', 'Measurement of GFR (mL/min) were as follows: no pre-WI, 2.1+/-0.26; pre-WI only, 1.24+/-0.14 (P<0.05 vs. no pre-WI); and pre-WI/ET-R antagonist, 2.3+/-0.45 (P<0.05 vs. pre-WI only and P=NS vs. no pre-WI).",
            "output": [
                "Does endothelin-receptor blockade mitigate the adverse effect of preretrieval warm ischemia on posttransplantation renal function in rats?"
            ]
        },
        {
            "id": "task847-8bb0e8bc08c04ee8800c7daed2f174c1",
            "input": "Fentanyl reduces the amount of propofol necessary to prevent responses to surgical stimuli. However, opioids have relatively little effect on consciousness. We, therefore, tested the hypothesis that fentanyl minimally alters the effect-site concentration of propofol associated with awakening. Fifty women having gynecologic laparotomy with propofol anesthesia were randomly allocated into the following target effect-site fentanyl concentrations: 0.8, 1.0, 1.4, 2.0, and 3.0 ng/mL. Fentanyl was continued at the designated rate through the initial postoperative phase. The propofol effect-site concentration associated with eye opening in response to verbal command was regarded as the awakening concentration. The estimated propofol effect-site concentrations at awakening did not differ significantly among the groups and were 1.9 +/- 0.5 micro g/mL with a fentanyl effect-site concentration of 0.8 ng/mL; 1.6 +/- 0.4 micro g/mL with 1.0 ng/mL of fentanyl; 1.6 +/- 0.2 micro g/mL with 1.4 ng/mL of fentanyl; 1.7 +/- 0.4 micro g/mL with 2.0 ng/mL of fentanyl; and 1.6 +/- 0.34 micro g/mL with 3.0 ng/mL of fentanyl (mean +/- SD). Seventy percent of the subjects in the 0.8 ng/mL fentanyl group spontaneously complained of pain, whereas none of the patients in the 2 or 3 ng/mL groups did. Five (56%) of 9 women in the 3 ng/mL group had a postoperative respiratory rate <6 breaths/min. Heart rate in one of these women decreased to <40 bpm. These data suggest that the optimal fentanyl effect-site concentration in patients recovering from gynecologic laparoscopy is between 1.4 and 2.0 ng/mL.",
            "output": [
                "Is effect-site concentration of propofol for recovery of consciousness virtually independent of fentanyl effect-site concentration?"
            ]
        },
        {
            "id": "task847-80cff1baabbe471487bda7d0fd078b6c",
            "input": "Agonism of alpha-adrenoreceptors has a powerful anesthetic result mediated, in part, by effects on the spinal cord. Alpha-adrenoreceptor agonists (e.g., dexmedetomidine) can decrease the minimum alveolar anesthetic concentration (MAC) of inhaled anesthetics (e.g., halothane) to zero, with an apparently additive interaction between halothane and dexmedetomidine. We tested whether the capacity of the inhaled anesthetic isoflurane to produce immobility in the face of noxious stimulation resulted from agonism of alpha-adrenoreceptors. MAC (the concentration required to eliminate movement in response to a noxious stimulus in 50% of subjects) of isoflurane was determined before and after intraperitoneal administration of the alpha-adrenoreceptor antagonists yohimbine and atipamezole. The doses of yohimbine and atipamezole equaled or exceeded those that reverse the ability of agonism of alpha-adrenoreceptors to decrease MAC. Smaller doses of yohimbine or atipamezole slightly increased (by 10%) the MAC of isoflurane, an increase we interpret as the result of blockade of a small amount of tonically active alpha-adrenoreceptor activity. Doses five-fold larger did not change MAC. Doses 10-fold larger decreased MAC. We conclude that alpha-adrenoreceptors do not or minimally mediate the capacity of inhaled anesthetics to produce immobility.",
            "output": [
                "Do alpha-2 adrenoreceptors probably mediate the immobility produced by inhaled anesthetics?"
            ]
        },
        {
            "id": "task847-98d89327ae0d434fbe2322c8dbde7342",
            "input": "Serious adverse outcomes from perioperative hypothermia are well documented. Consequently, intraoperative warming has become routine. We thus evaluated the efficacy of a novel, nondisposable carbon-fiber resistive-heating system. Twenty-four patients undergoing open abdominal surgery lasting approximately 4 h were randomly assigned to warming with 1) a full-length circulating water mattress set at 42 degrees C, 2) a lower-body forced-air cover with the blower set on high, or 3) a three-extremity carbon-fiber resistive-heating blanket set to 42 degrees C. Patients were anesthetized with a combination of continuous epidural and general anesthesia. All fluids were warmed to 37 degrees C, and ambient temperature was kept near 22 degrees C. Core (tympanic membrane) temperature changes among the groups were compared by using factorial analysis of variance and Scheff\u00e9 F tests; results are presented as means +/- SD. Potential confounding factors did not differ significantly among the groups. In the first 2 h of surgery, core temperature decreased by 1.9 degrees C +/- 0.5 degrees C in the circulating-water group, 1.0 degrees C +/- 0.6 degrees C in the forced-air group, and 0.8 degrees C +/- 0.2 degrees C in the resistive-heating group. At the end of surgery, the decreases were 2.0 degrees C +/- 0.8 degrees C in the circulating-water group, 0.6 degrees C +/- 1.0 degrees C in the forced-air group, and 0.5 degrees C +/- 0.4 degrees C in the resistive-heating group. Core temperature decreases were significantly greater in the circulating-water group at all times after 150 elapsed minutes; however, temperature changes in the forced-air and resistive-heating groups never differed significantly. Even during major abdominal surgery, resistive heating maintains core temperature as effectively as forced air.",
            "output": [
                "Are resistive-heating and forced-air warming comparably effective?"
            ]
        },
        {
            "id": "task847-331e8ecc1ea149e79e5f5c2af772f97f",
            "input": "To investigate serum levels of the advanced glycation end-products (AGEs) pentosidine and N epsilon-carboxymethyllysine (CML) in patients classified into different osteoporosis subgroups according to histomorphometric data.', 'Serum samples were obtained from 116 osteoporotic patients (34 men, 82 women) classified by bone histomorphometry into subgroups with high turnover (HTO, n = 32), low turnover (LTO, n = 39), normal turnover (NTO, n = 9) and cellular uncoupled osteoporosis (CUO, n = 36). Pentosidine was measured by high-performance liquid chromatography, and CML by a competitive enzyme-linked immunoassay.', 'The entire osteoporosis group had significantly higher pentosidine and CML serum concentrations than healthy subjects. In contrast to healthy subjects, no correlation between levels of AGEs and age could be found. In subgroups characterized by increased bone resorption (HTO, CUO), serum pentosidine correlated significantly with the histomorphometric marker reflecting osteoclast activity/bone resorption (eroded surface as a percentage of trabecular surface). Moreover, in CUO a strong correlation between pentosidine and the mineral apposition rate was found. Surprisingly, in HTO the levels of CML and percentage of eroded surface were significantly negatively correlated.",
            "output": [
                "Are advanced glycation end-products pentosidine and N epsilon-carboxymethyllysine elevated in serum of patients with osteoporosis?"
            ]
        },
        {
            "id": "task847-6bbd0db2a6ac4c2ba6231c892fb8d26a",
            "input": "Potassium transport via the potassium chloride cotransporter in rainbow trout erythrocytes is increased by high oxygen tension. It appears that the effect of oxygen is mediated by reactive oxygen species, especially hydroxyl radicals. In contrast, the activity of adrenergically stimulated sodium proton exchange decreases with increasing oxygen tension. As available data suggest that the two transporters are regulated reciprocally, the present study was undertaken to evaluate, if hydroxyl radicals may inhibit sodium transport via the adrenergically stimulated sodium proton exchanger.', 'The effects of the hydroxyl radical scavenger, 2 mm mercaptopropionyl glycine (MPG), on the activity of the adrenergically activated sodium proton exchange in rainbow trout erythrocytes were examined by measuring unidirectional sodium flux, using radioactive isotope, and cellular water content.', 'The activity of the sodium proton exchange increased with decreasing oxygen tension after adrenergic stimulation. When MPG was present during incubation, there was no statistically significant effect of oxygen tension on the adrenergically stimulated sodium proton exchange, whereby the activity of the transporter at atmospheric oxygen tension was markedly higher in the presence than in the absence of MPG. In the absence of adrenergic stimulation, MPG did not influence the transporter activity significantly at any oxygen tension.",
            "output": [
                "Is oxygen dependency of the adrenergic Na/H exchange in rainbow trout erythrocytes diminished by a hydroxyl radical scavenger?"
            ]
        },
        {
            "id": "task847-e0e0df13c5474c49ada85da9dcfdb1a2",
            "input": "The parenteral administration of oestradiol acutely protects against exercise-induced myocardial ischaemia in women, but whether this effect is sex-specific is not known.', 'The effects of acutely administered conjugated equine oestrogen on exercise-induced myocardial ischaemia in men with established coronary heart disease were investigated in a randomized, placebo-controlled, double-blind cross-over trial.', 'Twenty men, aged 62 +/- 11.6 years, with reproducible exercise-induced myocardial ischaemia were treated with either intravenous conjugated equine oestrogen (25 mg) or saline prior to undergoing an exercise stress test. Primary end-points were total exercise time and time to 1 mm ST-segment depression.', 'All participants completed the protocol. Total exercise time exceeded the baseline value in 17 of the 20 men following saline, and in 17 of the 20 men following oestrogen pretreatment. Time to 1 mm ST-segment depression exceeded the baseline value in 14 of the 19 men following saline, and following oestrogen administration, exceeded baseline in 13 of the 19 men. There was no significant difference between the two treatments in either time to 1 mm ST-segment depression or total exercise time. A period effect was apparent for total exercise time (P = 0.05) but not for time to ST-segment depression.",
            "output": [
                "Does acute administration of conjugated equine oestrogen improve exercise-induced myocardial ischaemia in men with coronary artery disease?"
            ]
        },
        {
            "id": "task847-00b4a45b553e44f182bbd4ab22846cd2",
            "input": "To ascertain whether a coding mutation (Ile93Met) in ubiquitin carboxy-terminal hydrolase (UCH-L1) gene plays a role in idiopathic Parkinson's disease (IPD).\", 'Polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) was used to distinguish the wild-type (two DNA fragments of 34 and 126 bp) from the variant allele (three fragments of 34, 60 and 66 bp) because the mutation created a new site for restriction endonuclease BsmF1. DNA was isolated from various blood samples using a phenolchloroform extraction.', 'Ile93Met substitution was found neither in PD patients nor in controls.",
            "output": [
                "Is an Ile93Met substitution in the UCH-L1 gene a disease-causing mutation for idiopathic Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-4d5f428ec83545eca0be4f4a15f9a6e0",
            "input": "Studies using self-report rating scales suggest a considerable overlap regarding symptom complaints in patients with fibromyalgia (FM) and functional dyspepsia (FD), while clinical assessments point to important psychological differences.', 'To test the hypothesis that measurement of psychological state by means of content analysis of speech will demonstrate differentiation between the two patient groups and between patients with these disorders and age-matched population-based random sample controls.', 'The Giessener Symptom Complaints Checklist assessed somatic complaints. The computerised Gottschalk-Gleser content analysis method assessed psychological state in 42 females with FM, 17 females with FD and 48 population-based, randomly selected control subjects.', 'FM patients score higher on mutilation anxiety than FD and control subjects. FD patients had the highest score for death anxiety. Mutilation anxiety and low hope score identified FM patients (sensitivity 68%, specificity 81%, overall classification 75%), but only 19% of the variation in total somatic complaints could be predicted from these or other psychological state scores. In FD patients, however, death anxiety explained 59% of the variance in gastrointestinal complaints.",
            "output": [
                "Does mutilation anxiety differ among females with fibromyalgia and functional dyspepsia and population controls?"
            ]
        },
        {
            "id": "task847-113511c1cb68416ca05cc8153c776e89",
            "input": "Psoriasis profoundly affects patient quality of life (QOL). Amevive (alefacept), a novel and selective biologic agent, was clinically effective and significantly improved QOL in a phase 2 study.', 'The present placebo-controlled, randomized phase 3 study examined the effects of a 12-week course of intramuscular alefacept on QOL in 507 patients with chronic plaque psoriasis using both dermatology-specific questionnaires [Dermatology Life Quality Index (DLQI); Dermatology Quality of Life Scales (DQOLS)] and the Short Form-36 Health Survey (SF-36), a generic, general health questionnaire.', 'All 3 QOL measures (DLQI, DQOLS, SF-36) demonstrated that alefacept 15 mg was significantly more effective than placebo in improving QOL in patients with chronic plaque psoriasis. In addition, the improvements in QOL for patients in the alefacept 15 mg group were of similar magnitude for all 3 QOL measures.",
            "output": [
                "Does intramuscular alefacept improve health-related quality of life in patients with chronic plaque psoriasis?"
            ]
        },
        {
            "id": "task847-a8e4be1bcc4a4c9ebe152608d41fe140",
            "input": "We developed an algorithm that prospectively defines when to excise the neurovascular bundles during radical retropubic prostatectomy with the goal of maximizing the performance of nerve sparing procedures while minimizing positive surgical margins.', 'From January 1 to December 31, 2000 a single surgeon performed 272 radical retropubic prostatectomies and 263 were performed from January 1 to December 31, 2001. A single pathologist analyzed all specimens with positive margins. There were no prospectively defined criteria to guide decisions regarding excision of the neurovascular bundles in the 2000 study cohort. Gleason score, percent tumor volume and perineural invasion were independently analyzed in the biopsy specimens according to the site of origin (right versus left side) for the 2001 group only. The ipsilateral neurovascular bundle was excised for Gleason 6 or less tumors when there were 50% or greater tumor volume in the biopsy specimen and perineural invasion, for Gleason 7 tumors when there was 30% or greater tumor volume, or perineural invasion and for Gleason 8 to 10 tumors when there was 10% or greater tumor volume, or perineural invasion.', 'There were no statistically significant differences between the 2000 and 2001 groups in regard to preoperative prostate specific antigen, clinical and pathological stage, biopsy Gleason score and percent tumor volume in the surgical specimen. There was a statistically significant decrease in the incidence of positive margins between the 2000 and 2001 groups (14% versus 8%, p = 0.027). The lower positive margin rate was not achieved because of a tendency to excise more neurovascular bundles since a significantly greater percent of neurovascular bundles was preserved in the 2001 group. The sensitivity, specificity, positive and negative predictive values, and accuracy of our algorithm were 18%, 93%, 28%, 89% and 84%, respectively. In sides of the prostate with extraprostatic extension ipsilateral wide excision of the neurovascular bundle was associated with positive margins in 33% of cases compared with 22% when the neurovascular bundle was preserved (p = 0.42).",
            "output": [
                "Does the New York University nerve sparing algorithm decrease the rate of positive surgical margins following radical retropubic prostatectomy?"
            ]
        },
        {
            "id": "task847-3b4e4bde7fc34da38e9d47c544b646a6",
            "input": "Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy.', 'A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy.', 'On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score.",
            "output": [
                "Is percent of prostate needle biopsy cores with cancer significant independent predictor of prostate specific antigen recurrence following radical prostatectomy : results from SEARCH database?"
            ]
        },
        {
            "id": "task847-da12759d14f046f990f0fe13cf9113a6",
            "input": "To study the impact of the new pharmacological treatment strategies in Parkinson's disease by analysis of the sales of dopaminergic drugs in Sweden 1990-2001.\", 'Invoice statistics and statistics on prescription sales of dopaminergic drugs 1990-2001 were obtained from the 906 public pharmacies and the 89 hospital pharmacies in Sweden. The Swedish Diagnosis and therapy survey was used to study the diagnosis the drugs were prescribed for.', 'During the period the sales expressed in DDD/1000 inhabitants and day increased from 1.75 to 1.86 (6%) for levodopa and from 0.04 to 0.27 (575%) for dopamine agonists. The increase in sales of dopamine agonists occurred after 1997 and consisted entirely of the sales of the new agonists, cabergoline, pramipexole and ropinirole. In Swedish crowns the total sales of dopaminergic drugs increased with 126% during the period. The cost for the dopamine agonists was 8% of the total cost for dopaminergic drugs in 1990 and 23% in 2001. The prescription sales figures of levodopa and dopamine agonists for the different Swedish counties in 2001 varied between 1.52 and 2.44 and 0.13 and 0.74 DDD/1000 inhabitants and day, respectively. There was no correlation, whether positive or negative, between the sales of dopamine agonists, levodopa and COMT inhibitors or between the sales and the densities of neurologists.",
            "output": [
                "Have the increased utilisation of dopamine agonists and the introduction of COMT inhibitors reduced levodopa consumption -- a nation-wide perspective in Sweden?"
            ]
        },
        {
            "id": "task847-fddbc0f28d4e488c92d96ac6850ee622",
            "input": "We assessed the clinical effectiveness of postoperative enteral stimulation by gut feeding in patients with severe acute pancreatitis (SAP).', 'Medical records of 63 patients who were operated on within the past 4 y due to deterioration of SAP were included in this retrospective study. Patients were stratified in gut feeding (GF; n = 33) and standard therapy (ST; n = 30) groups according to the postoperative therapy provided. The GF group received postoperative standard therapy and enteral stimulation by gut feeding, and the ST group received standard therapy only. The Acute Physiology and Chronic Health Evaluation II score, incidence of the systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), daily calories supply, complication rate, and outcomes were analyzed.', 'Patient characteristics did not differ between groups when considering age and severity of the disease. All patients underwent similar surgical interventions. SIRS and MODS were observed initially with the same frequency in both groups. Regression of MODS and a lower postoperative complication rate was observed more often in the GF group. Development of early pulmonary complications was observed in 12.1% to 13.3% in both groups, irrespective of the time of surgery. Subsequently, pulmonary complications developed in 15.2% of GF patients compared with 43.3% of ST patients (P <0.05). Acute renal insufficiency developed similarly in 33.3% of the GF patients and in 26.7% of the ST patients within 3 d after admission. Acute renal insufficiency developed later on only in the ST group (26.7%, P <0.05). Wound- and catheter-related septic complications were considerably more frequent in the ST group (30.0%) than in the GF group (9.1%, P <0.05). Intensive care and hospital stays did not differ. Postoperative gut feeding was associated with 6.1% mortality in the GF compared with 26.7% in the ST (P <0.05).",
            "output": [
                "Does postoperative enteral stimulation by gut feeding improve outcomes in severe acute pancreatitis?"
            ]
        },
        {
            "id": "task847-137fea679b6d4785b3d9980be556f8ea",
            "input": "Plasma high-density lipoprotein (HDL) level is inversely correlated with the risk of atherosclerosis. However, the cellular mechanism by which HDL exerts antiatherogenic actions is not well understood. In this study, we focus on the lipid components of HDL as mediators of the lipoprotein-induced antiatherogenic actions.', 'HDL and sphingosine 1-phosphate (S1P) stimulated the migration and survival of human umbilical vein endothelial cells. These responses to HDL and S1P were almost completely inhibited by pertussis toxin and other specific inhibitors for intracellular signaling pathways, although the inhibition profiles of migration and survival were different. The HDL-stimulated migration and survival of the cells were markedly inhibited by antisense oligonucleotides against the S1P receptors EDG-1/S1P1 and EDG-3/S1P3. Cell migration was sensitive to both receptors, but cell survival was exclusively sensitive to S1P1. The S1P-rich fraction and chromatographically purified S1P from HDL stimulated cell migration, but the rest of the fraction did not, as was the case of the cell survival.",
            "output": [
                "Does high-density lipoprotein stimulate endothelial cell migration and survival through sphingosine 1-phosphate and its receptors?"
            ]
        },
        {
            "id": "task847-d9963174d3c34557a1bef49a278bd228",
            "input": "Glycoprotein (GP) Ibalpha is the functionally dominant subunit of the platelet GPIb-IX-V receptor complex. The N-terminal domain of the GPIbalpha chain contains binding sites for alpha-thrombin and von Willebrand factor (VWF). The human platelet alloantigen (HPA)-2 polymorphism of the GPIbalpha gene is associated with a C/T transition at nucleotide 1018, resulting in a Thr/Met dimorphism at residue 145 of GPIbalpha. To study the structural and functional effects of this dimorphism, N-terminal fragments (AA1-289) of the HPA-2a and HPA-2b alloform of GPIbalpha expressed in CHO cells were used.', 'Of 74 moAbs directed against human GPIbalpha, 2 antibodies with epitope between AA1-59 could differentiate between both alloforms. In addition, VWF bound with a higher affinity to the recombinant HPA-2a fragment or to homozygous HPA-2a platelets. In contrast, no difference was found in the binding of alpha-thrombin to the recombinant alloform fragments or of antibodies directed against the alpha-thrombin binding anionic sulfated tyrosine sequence (AA269-282).",
            "output": [
                "Is von Willebrand factor but not alpha-thrombin binding to platelet glycoprotein Ibalpha influenced by the HPA-2 polymorphism?"
            ]
        },
        {
            "id": "task847-087d88b9c9e845faa88e1bfc4fbb8ebd",
            "input": "We have previously shown that phospholipid oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) inhibit lipopolysaccharide (LPS)-induced E-selectin expression and neutrophil binding in human aortic endothelial cells (HAECs). The current studies identify specific phospholipids that inhibit chemokine induction by Toll-like receptor-4 (TLR4) and -2 (TLR2) ligands inECs and macrophages.', 'Measurements of interleukin (IL)-8 and monocyte chemotactic protein-1 levels secreted from ox-PAPC- and LPS-cotreated ECs indicate that ox-PAPC inhibits activation of TLR4 by LPS. The effects of IL-1beta and tumor necrosis factor-alpha, which utilize the same intracellular signaling molecules, were not inhibited. Cell fractionation and immunofluorescence analyses demonstrate that LPS induces membrane translocation of the LPS receptor complex to a lipid raft/caveolar fraction in ECs. Ox-PAPC inhibits this translocation and alters caveolin-1 distribution. Supporting an important role for caveolae in LPS action, overexpression of caveolin-1 enhanced LPS-induced IL-8 synthesis. Ox-PAPC also inhibits the effect of TLR2 and TLR4 ligands in human macrophages.",
            "output": [
                "Do specific phospholipid oxidation products inhibit ligand activation of toll-like receptors 4 and 2?"
            ]
        },
        {
            "id": "task847-ab459e20b89f4e50804abd327e03d83c",
            "input": "The salt-sensitive Dahl rat and the spontaneously hypertensive rat develop comparable spontaneous hypertension on a low-salt diet, whereas only the salt-sensitive Dahl rat strain develops a striking increase in blood pressure and cardiovascular hypertrophy on a high-salt diet. We set out to identify quantitative trait loci (QTLs) contributing to the progression of salt-induced organ damage in hypertension by studying an F2 population derived from both strains.', 'We determined systolic blood pressure (SBP), vascular aortic hypertrophy (AH), cardiac left ventricular (LV) hypertrophy (LVH), and LV fibrosis in 230 male F2-animals on a high-salt diet. A strong correlation between AH and LVH was found (r=0.58, P<0.0001), and genome-wide QTL mapping detected suggestive or significant QTLs in overlapping chromosomal fragments for AH and LVH on chromosomes 1, 3, and 19, respectively. A significant influence of SBP on the extent of LVH and AH was evident at all QTLs, although significant linkage to SBP (together with LVH) was only found on chromosome 9. No QTLs for LV fibrosis were detected.",
            "output": [
                "Do genetic loci contribute to the progression of vascular and cardiac hypertrophy in salt-sensitive spontaneous hypertension?"
            ]
        },
        {
            "id": "task847-39044c3d16a043ffa31c17dda62a7ad5",
            "input": "Magnetic Resonance Imaging (MRI) allows a detailed \"in vivo\" macroscopic study of the human brain; previously, it has been demonstrated that Fluid Attenuated Inversion Recovery (FLAIR) sequence shows higher signal intensity of cortices belonging to limbic structures.', 'To measure and compare signal intensities (SI) of cytoarchitectonically different cortical regions.', 'In 22 adult subjects, without psychiatric or neurological diseases, FLAIR sequence was performed in coronal slices, perpendicular to the main hippocampal axis. Signal intensity was measured, with a region-of-interest (ROI) function, in 12 different cortical regions. We compared these values and grouped the cortices into five groups: (1) limbic cortices, (2) paralimbic agranular cortices, (3) paralimbic granular cortices, (4) parietal-type neopallium, (5) frontal-type neopallium. A t-test for comparison of paired samples was performed, considering p</=0.05 as statistically significant.', 'We found statistically significant differences amongst the different groups, with the exception of groups 1 and 2, which did not show differences between them. No statistically significant differences were found among cortices belonging to the same group.",
            "output": [
                "Does magnetic resonance imaging identify cytoarchitectonic subtypes of the normal human cerebral cortex?"
            ]
        },
        {
            "id": "task847-95a330e872eb4a6b9c4b61f694346dd3",
            "input": "To evaluate whether calcium adjusted for albumin can be used to monitor calcium homeostasis in critically ill patients.', 'Prospective single-single center observational study.', 'Clinical laboratory and critical care unit of a regional teaching hospital.', 'Fifty-three paired samples were from 36 patients requiring intensive care treatment.', 'None.', 'Total calcium, albumin-adjusted calcium, and ionized calcium were measured in critically ill patients during an 8-wk period. Calcium was adjusted for albumin using the formula that is most frequently used in The Netherlands. Using ionized calcium as the gold standard, albumin-adjusted calcium overestimated hypercalcemia and totally missed hypocalcemia. The same seemed to be true for other formulas used for albumin or protein adjustment of calcium concentrations.",
            "output": [
                "Is albumin-adjusted calcium suitable for diagnosis of hyper- and hypocalcemia in the critically ill?"
            ]
        },
        {
            "id": "task847-345f5aa65eb04b34a9e6010a79b681a8",
            "input": "To demonstrate the chemical constituents of Alyxia sinensis.', 'Phytochmical experiment was carried out, using column chromatograph technologies.', 'Five compounds have been isolated from the petroleum ether soluble part of the stems of A. sinensis. Their structures have been elucidated respectively as heptatriacontane(1), octatriacontane(2), 20-noatriacontannone(3), 20-nonatriacontanone(4), 20-tetraacontanoe(5), physcion(6), emodin(7), chrysophanol(8), coumarin(9), stigmasterol acetate(10), beta-sitosterol acetate(11), lupeol(12), betulin(13), stigmasterol(14), beta-sitosterol(15), ursolic acid(16), oleanolic acid(17).",
            "output": [
                "Does [ Studies on the chemical constituents of the stem of Alyxia sinensis ( I ) ]?"
            ]
        },
        {
            "id": "task847-37af3acd139e4fcdb75c81f82b69af9d",
            "input": "People with a history of rheumatic fever (RF) are at high risk of recurrent attacks and of developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of RF and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin.', 'To assess the effects of different penicillin regimens and formulations for preventing streptococcal infection and RF recurrence.', 'We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), Medline (January 1966-July 2000), Embase (January 1985-July 2000), reference lists of articles, and contacted experts in the field.', 'Randomised and quasi-randomised studies comparing: (i) oral with intramuscular penicillin; and (ii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous RF.', 'Two reviewers independently assessed trial quality and extracted data.', 'Six studies were included (1,707 patients). Data were not pooled because of clinical and methodological heterogeneity of the trials. Four trials (1,098 patients) compared intramuscular with oral penicillin and all showed that intramuscular penicillin was more effective in reducing RF recurrence and streptococcal throat infections than oral penicillin. One trial (360 patients) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every 2 weeks was better at reducing RF recurrence (relative risk (RR) 0.52, 95% confidence interval (CI): 0.33-0.83) and streptococcal throat infections (RR 0.60, 95% CI: 0.42-0.85). One trial (249 patients) showed that 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI: 0.48-0.92) compared with 4-weekly intramuscular penicillin.",
            "output": [
                "Is intramuscular penicillin more effective than oral penicillin in secondary prevention of rheumatic fever -- a systematic review?"
            ]
        },
        {
            "id": "task847-98d0afd0cf1248aabbcea32b9010c292",
            "input": "To describe a novel form of pontocerebellar hypoplasia (PCH) and map its genetic locus.', 'PCH is a heterogeneous group of disorders that are characterized by abnormally small cerebellum and brainstem. Autosomal recessive inheritance has been implied in many cases, but no genetic loci have been mapped to date.', 'The authors studied a consanguineous family from the Sultanate of Oman with three siblings with a novel form of PCH. The authors performed clinical studies and linkage analysis of this pedigree.', 'The clinical features of the affected children include developmental delay, progressive microcephaly with brachycephaly, seizures during the first year of life, hypotonia with hyperreflexia, short stature, and optic atrophy. Imaging studies showed a small pons and cerebellum, prominent sulci and lateral ventricles, and decreased cerebral white matter volume. A lack of dyskinesias distinguishes this pedigree from PCH type 2. Genetic studies of this family revealed evidence of significant linkage to chromosome 7q11-21 (maximum multipoint lod score 3.23).",
            "output": [
                "Does a novel form of pontocerebellar hypoplasia map to chromosome 7q11-21?"
            ]
        },
        {
            "id": "task847-c663f2fadbfe40bfb0ab95964a916ee6",
            "input": "To determine the diagnostic and prognostic value the bone marrow aspiration in children with severe deficiency anaemia.', 'In this retrospective study we analysed 75 children 0-4 years of age who were diagnosed and treated from severe anaemia (Hb < 8g/dl) at Haematologic outpatient and hospital department of Pediatric Clinic in Sarajevo in period of 01.01.1999. to 31.12.1999.', 'We analyzed totally 75 children--37 (49.33%) boys and 38 (50.67%) girls. Morphologic finding of bone marrow aspirate smear showed: features of ferriprive flora in 24% of analyzed patients; dimorphic bone marrow features in 9.3% of patients; feriprivic flora with dyshematopoesis in 62.7% and megaloblasic anaemia features in 1.3% of analyzed patients. In two children we diagnosed leukemias from bone marrow aspirate; one was ALL/L2 and the second was AML/M2 leukemia.",
            "output": [
                "Does [ Diagnostic value and cytomorphologic findings in bone marrow puncture in children with severe deficiency anemia ]?"
            ]
        },
        {
            "id": "task847-1c58d7905bcf4fa0ae859ac070206ec5",
            "input": "To determine whether macrophages in human reproductive tissues contain luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor mRNA and receptor protein that can bind 125I-hCG.', 'Macrophages isolated from term pregnancy human decidua were used for LH/hCG receptor detection by in situ hybridization for receptor mRNA and immunocytochemistry for a macrophage marker, CD68, performed alone and in combination, reverse transcription-nested polymerase chain reaction, Western and ligand blotting. The LH/hCG receptor presence in macrophages in late luteal phase human endometria and corpora lutea was determined by sequential performance of in situ hybridization and immunocytochemistry.', 'The macrophages present in term pregnancy human decidua and late luteal phase human endometria and corpora lutea contain LH/hCG receptors.",
            "output": [
                "Do macrophages in human reproductive tissues contain luteinizing hormone/chorionic gonadotropin receptors?"
            ]
        },
        {
            "id": "task847-66de55ebed2840f18d4a2012f334fd74",
            "input": "Reduced fertilization rates in women with minor endometriosis may be the result of direct effects on the ovary or to primary dysfunction within the hypothalamic-pituitary-ovarian axis. This controlled study was designed to examine the steroidogenic potential of luteinized granulosa cells in women with minor endometriosis.', 'Granulosa cells were harvested at oocyte recovery and incubated for 3 hr in increasing concentrations of luteinizing hormone (LH). The dissociation constant for added concentrations of LH was computed (as Km LH) and the results were compared between women with endometriosis and controls.', 'Women with minor endometriosis had a higher dissociation constant than women with tubal damage [Km 0.98 (0.58-9.24) versus 0.33 (0.28-0.72) ng/mL, P = 0.019], indicating reduced sensitivity to LH.",
            "output": [
                "Are pre-ovulatory granulosa cells of infertile women with endometriosis less sensitive to luteinizing hormone?"
            ]
        },
        {
            "id": "task847-199f222ae0714060b62b78adeff9ffdf",
            "input": "Endostatin is a cleaved fragment of collagen Type XVIII and has antiangiogenic activity. The clinical significance of circulating, soluble endostatin (S-endostatin) is not known.', 'Pretreatment S-endostatin and serum vascular endothelial growth factor (S-VEGF) levels were measured in 143 patients with non-Hodgkin lymphoma (NHL) using competitive enzyme immunoassays and were compared with the levels from a control group (n = 24 participants).', 'S-endostatin levels varied widely from 4.5 ng/mL to 116 ng/mL (median, 29.6 ng/mL), and the median level was higher in patients with NHL compared with patients in the control group (16.4 ng/mL; P = 0.05). High S-endostatin levels were associated with advanced disease stage (P < 0.0001) and high serum VEGF levels at diagnosis (P = 0.017). The median 5-year survival rate for patients who had S-endostatin concentrations within the highest tertile (> 36.0 ng/mL) was only 34% compared with 57% in patients who had lower S-endostatin levels (P = 0.019). A high S-endostatin level also was associated with a poor outcome in patients with large cell diffuse and immunoblastic lymphoma, which was the largest subgroup within the series (n = 60 patients). Patients who had high pretreatment levels of both S-VEGF and S-endostatin had particularly poor outcomes. High S-endostatin levels had an independent, adverse influence on survival it was entered as a factor into a multivariate analysis together with the factors included in the International Prognostic Index (relative risk, 1.80; 95% confidence interval, 1.08-2.98; P = 0.0024).",
            "output": [
                "Is elevated serum endostatin associated with poor outcome in patients with non-Hodgkin lymphoma?"
            ]
        },
        {
            "id": "task847-99b989b0b331437c85c639fcce453336",
            "input": "The aim of the present study was to determine the potential therapeutic value of the lazaroid U-83836E on blood brain barrier (BBB) breakdown and edema with respect to the changes in the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-adenosinetriphosphatase (ATPase) activities, tissue malondialdehyde levels and the neuronal viability in the rat brain subjected to cerebral trauma.', 'Traumatic brain injury (TBI) was introduced by applying a 75 gm. cm force to the right parietal cortex using the weight-drop method. The first set of animals was used for determining time course changes of the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-ATPase and the malondialdehyde levels and were sacrificed 2, 6 and 24h after lesion production. A group of the animals was treated with U-83836E proir to TBI and sacrificed 24h after cerebral injury. A second set of animals was used for evaluating the alterations in BBB disruption and tissue water content and were sacrificed 2, 6 and 24h after lesion production. Two groups of animals were treated with U-83836E and sacrificed after 2 and 24h following TBI. U-83836E was given intraperitoneally thirty minutes before trauma at a dose of 10 mg/kg. Neuronal necrosis was also evaluated in the groups of U-83836E and physiological saline-treated animals.', 'Extravasation of Evans blue into the traumatized hemisphere was maximum at 2h (p<0.001) and returned close to the control levels at 24h after TBI (p>0.05). Edema had developed progressively over time and reached the maximum degree of 2.1% (p<0.001) at 24h. U-83836E showed no effect on the BBB breakdown and the tissue water content at 2h and still had no effect on the BBB breakdown after 24h following the trauma (p>0.05), although it reduced edema after 24h (p<0.01). The losses of Na+/K+ and Mg(2+)/Ca(2+)-ATPase activities were found as 39.5% (p<0.001) and 29.4% (p<0.01) of the control value, respectively, and remained at the decreased levels throughout the experiment. Malondialdehyde level continued to increase over time reaching up to 209% (p<0.001) of the control value 24h after TBI. Both ATPase activities were improved to near control values (p>.05) by the effect of U-83836E. U-83836E inhibited the increase of lipid peroxidation (p<0.001) and also salvaged neuronal necrosis (p<0.05).",
            "output": [
                "Does lazaroid attenuate edema by stabilizing ATPase in the traumatized rat brain?"
            ]
        },
        {
            "id": "task847-96d805f0f14f4853b4e0e46174d63480",
            "input": "To test device integrity and objective auditory reaction for cochlear implant patients intraoperatively.', 'Our protocol for intraoperative testing of the implant device includes device electrode impedance test and neural response telemetry (NRT), which measures the electrically evoked auditory nerve compound action potentials (ECAP).', 'We completed electrode integrity tests and NRT intraoperatively on 40 patients with the Nucleus CI24M cochlear implant. We have measured normal implant function on all 40 patients and obtained ECAP results from 39 patients. Out of 33 patients with normal inner ear, typical ECAPs were recorded in 195 electrodes in all 198 testing electrodes(98.5%). In 7 patients with inner ear Mondini dysphasia, affirmative ECAP waveforms were recorded in 26 electrodes in all 42 testing electrodes. The basal electrode ECAP threshold was higher than that of the epical one.",
            "output": [
                "Do [ The intraoperative application of neural response telemetry with the nucleus CI24M cochlear implant ]?"
            ]
        },
        {
            "id": "task847-fe1c197c6c9c43c2b2b099da664a5ad7",
            "input": "To identify risk factors for subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, we designed a case-control study of men and women 18 to 49 years of age (the Hemorrhagic Stroke Project [HSP]). This report focuses on SAH.', 'Patients were recruited from 44 hospitals in the United States. Cases with SAH must have had a ruptured aneurysm documented by angiography or surgery. Two controls, identified by random digit dialing and matched to each patient for age, sex, race, and telephone exchange, were sought for each case subject.', 'Between 1994 and 1999, 425 patients with SAH were enrolled in HSP, and 312 cases met the criteria for aneurysmal SAH. The present analyses also included 618 matched controls. Of the 312 cases, 66% were current cigarette smokers compared with 30% of controls (adjusted odds ratio [OR], 3.73; 95% CI, 2.67 to 5.21). Cocaine use within the previous 3-day period was reported by 3% of cases and no controls (bivariate exact OR, 24.97; 95% exact CI, 3.95 to infinity; adjusted estimate not calculable). Other independent risk factors in the multivariable model included hypertension (adjusted OR, 2.21; 95% CI, 1.48 to 3.29), low body mass index (OR, 1.59; 95% CI, 1.08 to 2.35), primary family history of hemorrhagic stroke (OR, 3.83; 95% CI, 1.73 to 8.46), caffeine in pharmaceutical products (OR, 2.48; 95% CI, 1.19 to 5.20), lower educational achievement (OR, 2.36; 95% CI, 1.44 to 3.87), and nicotine in pharmaceutical products (adjusted estimate not calculable).",
            "output": [
                "Are major risk factors for aneurysmal subarachnoid hemorrhage in the young modifiable?"
            ]
        },
        {
            "id": "task847-acc70736ee064d2baf862aaf3cc35836",
            "input": "To evaluate the quality of pain assessment by emergency medical services (EMS) in out-of-hospital emergencies.', \"A prospective study was conducted on a convenience sample of patients during a one-year observation period. Pain ratings assessed by emergency patients were documented at three different intervals during the emergency call, and compared with concomitant assessments by EMS providers. A visual analog scale (VAS) and a verbal pain scale (VPS) were used for pain assessment. Repeated-measures ANOVA and Dunnett's t-test were used for data analysis.\", 'Fifty-one out of 70 eligible patients met inclusion criteria. In most emergency patients the intensity of pain was underestimated by EMS, especially when pain was severe (p = 0.0001). During the course of transport, both pain and pain assessment by EMS improved significantly (p = 0.0001). The VAS and VPS were significantly correlated (p = 0.0001).",
            "output": [
                "Is acute pain underassessed in out-of-hospital emergencies?"
            ]
        },
        {
            "id": "task847-d5121d1f6ce94c88aa274d404e5589a2",
            "input": "Objective analysis of surgical skill is necessary. A novel method of assessment using simple error analysis in synthetic models is examined for construct validity.', 'Two examination protocols were devised using synthetic models. These contained either a purpose made error or were representative of good surgical practice. Protocol one contained models of skin closure and minor operations. Protocol two in addition more complex procedures. Face validity was established by the approval of senior surgeons. Junior surgeons were recruited to undertake the assessment. A p value of less than 0.05 was deemed to be significant.', 'Eighty-nine surgeons were recruited. Both protocol one and two were able to discriminate between groups at statistically significant levels.",
            "output": [
                "Is the surgical error examination a novel method for objective technical knowledge assessment?"
            ]
        },
        {
            "id": "task847-91ab1e2405b043cb9f6d7ec644d574e6",
            "input": "Hypertension of the recipient is strongly associated with chronic allograft nephropathy. It is unclear, however, whether hypertension is the cause or the consequence of chronic allograft nephropathy.', 'The present study was performed in the Fisher to Lewis rat kidney transplant model. Transplanted rats (N = eight in each group) received either no treatment or were made hypertensive by administration of deoxycorticosteron acetate (DOCA) and salt. Proteinuria and systolic blood pressure was measured monthly, grafts were harvested at 3 and 6 months for semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and for immunohistology.', 'Systolic blood pressure was markedly elevated in rats receiving DOCA/salt. Allografts of hypertensive animals contained significantly more cells expressing the proliferating cell nuclear antigen compared to isografts and to allografts from normotensive animals (P < 0.05). Histologic staining and mRNA expression of major histocompatibility complex (MHC) II was markedly increased in allografts of hypertensive animals compared to all other groups (P < 0.05). Expression of mRNA for platelet-derived growth factor-B (PDGF-B), transforming growth factor-beta (TGF-beta) and collagen was higher in allografts than in isografts and was highest in hypertensive animals.",
            "output": [
                "Does hypertension increase expression of growth factors and MHC II in chronic allograft nephropathy?"
            ]
        },
        {
            "id": "task847-7ffd54a1a8e14e709699f2dba6cf9281",
            "input": "Both solid and hollow visceral abdominal injuries have been associated with the use of seat belts in children involved in motor vehicle crashes. The relationship between the types of restraint used and the pattern of abdominal injury is unknown.', \"A probability sample of restrained children involved in crashes was enrolled in an ongoing crash surveillance system (1998 through 2002) linking insurance claims data to telephone survey and crash investigation data. Significant abdominal injuries were considered when the Abbreviated Injury Scale (AIS) score was > or =2 and were defined as hollow visceral (HV; intestine, bladder), or solid visceral (liver, spleen, pancreas, kidney). Restraint type was categorized as optimal restraint (OR) or suboptimal restraint (S-OR) based on the child's age and size.\", 'For the 33 months of review, interviews were obtained for 13,558 restrained children aged 0 to 15 years, of which, 56% were OR (n = 7,591) and 44% were S-OR (n = 5,967). A significant abdominal injury was recorded in 78 children. A hollow visceral injury was recorded in 38 (9 OR and 29 S-OR), and a solid visceral injury in 32 (18 OR and 14 S-OR). Both hollow and solid visceral injuries were present in 8 children (2 OR and 6 S-OR). Suboptimally restrained children had a higher risk for hollow visceral injury when compared with optimally restrained children (Odds Ratio, 4.14 [95% Confidence Interval 1.33 to 13.22, P <.01]).",
            "output": [
                "Does suboptimal restraint affect the pattern of abdominal injuries in children involved in motor vehicle crashes?"
            ]
        },
        {
            "id": "task847-3d9bff49af3549bd84e2cf581ca89948",
            "input": "To examine the inhibition of nitric oxide (NO) synthesis during ischemic preconditioning (IP) upon the induction of heat-shock protein 72 (HSP72) and the size-limiting effect of the second window of protection on infarction.', 'Rabbits were subjected to either 4 cycles of 5-min long coronary artery occlusion separated by 10 min of reperfusion, or a sham operation. During this procedure, we administered 10 mg/kg of N(G)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) intravenously 5 min before IP followed by its continuous infusion (1.5 mg/kg/min). Twenty-four hours after IP or the sham operation, the hearts were rapidly excised for assay of HSP72 expression or were subjected to 30 min of coronary artery occlusion followed by 120 min of reperfusion, at which point infarct size (IS) was measured.', 'Twenty-four hours after IP or the sham operation, there was no difference in heart rate or mean arterial pressure between the groups. Immunoblotting revealed an increase in HSP72 protein levels in the IP group, which was blocked by L-NAME. IS in the IP rabbits was reduced compared with controls (29.8 +/- 3.7% vs. 50.8 +/- 4.3%, P < 0.01). IS in the IP rabbits was elevated as a result of L-NAME treatment (46.0 +/- 5.1%). Administration of L-arginine reversed the effects of L-NAME on the induction of HSP72 and IS (33.5 +/- 4.0%). The intravenous administration of S-nitroso-N-acetylpenicillamine (an NO donor, 15 microg/kg/min) over 20 min increased the induction of HSP72 and reduced IS (31.3 +/- 5.7%, P < 0.01 vs. control) 24 h later.",
            "output": [
                "Does nitric oxide open second window of protection in ischemic preconditioning via induction of heat-shock protein 72?"
            ]
        },
        {
            "id": "task847-564307c1ae4e4d01962d8c00764149a6",
            "input": "Hemodynamic forces affect smooth muscle cell (SMC) proliferation and migration both in vitro and in vivo. However, the effects of oscillatory shear stress (SS) on SMC proliferation and signal transduction pathways that control survival are not well described.', 'Bovine aortic SMC were exposed to arterial levels of oscillatory SS (14 dyne/cm(2)) with an orbital shaker; control cells were exposed to static conditions (0 dyne/cm(2)). Cell number and (3)[H]thymidine incorporation were measured after 1, 3, or 5 days of SS. Activation of the Akt pathway was assessed with the Western blot technique. Specificity of the phosphatidylinositol 3-kinase (PI3K) pathway was determined with the Western blot technique with the inhibitors LY294002 (10 micromol/L) or wortmannin (25 nmol/L).', 'Arterial levels of oscillatory SS increased SMC cell number by 20.1 +/- 3.7% and (3)[H]thymidine incorporation by 33.4% +/- 6.8% at 5 days. To identify whether SS increased activity of the SMC survival pathway, Akt activation was measured. SMC exposed to SS demonstrated increased Akt phosphorylation compared with control cells, with maximal phosphorylation at 60 minutes. Both PI3K inhibitors specifically inhibited the increase in Akt phosphorylation in SMC exposed to oscillatory SS.",
            "output": [
                "Does oscillatory shear stress increase smooth muscle cell proliferation and Akt phosphorylation?"
            ]
        },
        {
            "id": "task847-419f074861114fbdb3655a9e852cc20c",
            "input": "To determine whether a simple question about steadiness at admission predicts in-hospital functional decline and whether unsteadiness at admission predicts failure of in-hospital functional recovery of patients who have declined immediately before hospitalization.', 'Prospective cohort study.', 'One university hospital and one community teaching hospital.', 'One thousand five hundred fifty-seven hospitalized medical patients aged 70 and older.', 'On admission, patients reported their steadiness with walking and whether they could perform independently each of five basic activities of daily living (ADLs) at admission and 2 weeks before admission (baseline). For the primary analysis, the outcome was decline in ADL function between admission and discharge. For the secondary analysis, the outcome was in-hospital recovery to baseline ADL function in patients who experienced ADL decline in the 2 weeks before admission.', 'In the primary cohort (n = 1,557), 25% of patients were very unsteady at admission; 22% of very unsteady patients declined during hospitalization, compared with 17%, 18%, and 10% for slightly unsteady, slightly steady, and very steady patients, respectively (P for trend =.001). After adjusting for age; medical comorbidities; Acute Physiology, Age, and Chronic Health Evaluation II score; and admission ADL, unsteadiness remained significantly associated with ADL decline (odds for decline for very unsteady compared with very steady = 2.6, 95% confidence interval = 1.5-4.5). In the secondary analysis, predicting ADL recovery in patients who declined before hospitalization (n = 563), 46% of patients were very unsteady at admission. In this cohort, 44% of very unsteady patients failed to recover, compared with 35%, 36%, and 33% for each successively higher level of steadiness, respectively (P for trend = 0.06). After multivariate adjustment, greater unsteadiness independently predicted failure of recovery (P for trend = 0.02).",
            "output": [
                "Does unsteadiness reported by older hospitalized patients predict functional decline?"
            ]
        },
        {
            "id": "task847-3ba547d3b53746b19f2f9ff935f46ece",
            "input": "Hepatocyte growth factor/scatter factor (HGF/SF) can sufficiently and independently induce pathophysiological angiogenesis. However, the treatment strategies have mostly been unsuccessful. The present study is the first to evaluate the possible targeting of downstream signals for the inhibition of HGF/SF-induced angiogenesis.', 'In a multichannel scratch assay with human endothelial cells (ECs), HGF/SF induced a strong and prolonged activation of MAPK and cell proliferation that was inhibited by PD98059 and LY294002/wortmannin, selective inhibitors of MAPK and PI3K signaling modules, respectively. Western blotting demonstrated a temporal relation between the activation of the two pathways. Chemical inhibition of the PI3K and MAPK signals inhibited HGF/SF-induced chemoinvasion of ECs in vitro and blocked the HGF/SF-induced neovascularization into a polymer scaffold in vivo, as quantified by vessel counts and the clearance of radioactive 133Xe.",
            "output": [
                "Does targeting of mitogen-activated protein kinases and phosphatidylinositol 3 kinase inhibit hepatocyte growth factor/scatter factor-induced angiogenesis?"
            ]
        },
        {
            "id": "task847-62e7e04948aa443f93ca8b5646ff2e69",
            "input": "We evaluated the adequacy of nutrient intake in comparison with the Indonesian Estimated Average Requirement (EARs) among pregnant Indonesian women and explain the short-term effect of economic crisis on nutrient intake and iron status.', 'Cross-sectional study.', 'Purworejo District, Central Java, located 60 km west of Yogyakarta Province, Indonesia.', 'During the period from 1996 to 1998, up to six 24 h recalls were performed during the second trimester of pregnancy among 450 women. Nutrient intake and iron status was evaluated in relation to date of data collection relative to the economic crisis that emerged in August 1997. A computer program (Inafood) was developed to calculate nutrient intake.', ': Forty percent of the pregnant women were at risk of inadequate intake of energy and protein, and 70% were at risk of inadequate intake of vitamin A, calcium and iron even before the crisis. Our results also demonstrate an effect of short-term economic crisis on nutrient intake and iron status. When the crisis emerged, urban poor experienced a decrease in intake of most nutrients. During the crisis, rich women experienced a significant decrease in fat (P<0.05). Negative changes in fat density during crisis were experienced by the rich and the rural, poor, and access to rice field subgroups (P<0.01). A significant increase in carbohydrate densities was seen for the rich and rural, poor, and access to rice fields groups (P<0.05). Urban poor experienced decreased serum ferritin concentration (P<0.05), whereas rich women experienced a significant increase (P<0.05).",
            "output": [
                "Are nutrient intake and iron status of urban poor and rural poor without access to rice fields affected by the emerging economic crisis : the case of pregnant Indonesian women?"
            ]
        },
        {
            "id": "task847-a37c2f8a9b334022837d1d8c71f78c1d",
            "input": "In the rat, two forms of the pancreatic secretory trypsin inhibitor, PSTI-I and PSTI-II, are secreted into pancreatic juice. It is assumed that their role is to protect the pancreas from premature activation of the protease-rich pancreatic juice. In the small intestine, PSTI-I, also called 'monitor peptide', is thought to have a different role: PSTI-I competes with protein for activated trypsin. In the presence of a protein-rich meal, free PSTI induces a release of cholecystokinine from the intestine.\", 'To investigate whether its role as monitor peptide is compatible with the inhibitory, protective function in the pancreas, PSTI-I was chemically synthesized and then renatured.', 'The peptide was almost completely trypsin resistant and exhibited a dose-dependent inhibitory activity to bovine and partially purified rat trypsin. Furthermore, experiments with trypsin- and endopeptidase-activated pancreatic juice demonstrated that its inhibitory capacity was sufficient to prevent premature activation. Binding studies of (125)I-labeled PSTI-I with the putative intestinal receptor using isolated membranes indicated the presence of high-affinity binding sites (k(d) = 5 x 10(-8)M). Binding of PSTI-I could be competed with excess PSTI-I or trypsin. In a biological assay system, injections of PSTI-I displayed monitor peptide activity by inducing a dose-dependent trypsinogen release from the pancreas.",
            "output": [
                "Does the bifunctional rat pancreatic secretory trypsin inhibitor/monitor peptide provide protection against premature activation of pancreatic juice?"
            ]
        },
        {
            "id": "task847-5d70a8728c10463d875e47b638c0e157",
            "input": "To investigate whether different procedures of topical medication interfere with postoperative face-down positioning and thereby influence the anatomical success rate of macular hole surgery.', 'A total of 39 consecutive eyes with macular holes were operated with vitrectomy and fluid-gas exchange, followed by face-down positioning for 1 week. Postoperatively, the procedures for topical medication differed between two consecutive groups of patients. In the first group (16 patients), a conventional postoperative regimen of topical antibiotics and steroids was administered as eye drops six times daily. In the second group (23 patients), topical medication was administered as ointments once daily, while the patients kept their heads straight forwards and looked slightly downwards.', 'The macular hole closed successfully in 10 (62.5%) of the 16 eyes in the eye drop group, and in 21 (91.3%) of the 23 eyes in the ointment group (p < 0.05).",
            "output": [
                "Does topical medication interfere with face-down positioning after macular hole surgery?"
            ]
        },
        {
            "id": "task847-9379a4d53f86471bb81367dcfecf3b74",
            "input": "It has been reported previously that the paired interpretation of the corticotrophin-releasing hormone (CRH) test and the 8-mg dexamethasone suppression test (HDDST) could have higher diagnostic power than any single test in the differential diagnosis of ACTH-dependent Cushing's syndrome. This finding has not been confirmed thereafter in large series. The aim of the present study has been to assess the operating characteristics of either the CRH test or the overnight HDDST and also to evaluate the potential utility of combining the interpretation of both tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.\", \"We have reviewed the medical records of 59 consecutive cases with ACTH-dependent Cushing's syndrome: 49 patients with proven Cushing's disease (CD) and 10 patients with proven ectopic ACTH syndrome (EAS). Univariate curves of the receiver operating characteristics (ROC) have been performed to define the best cut-off values, the sensitivity and the specificity for CRH and overnight HDDST. A comparison between the areas under the ROC curves has also been performed.\", 'For the CRH test, the point on the ROC curve closest to 1 corresponded to a value of ACTH percentage increment of 50%[sensitivity 86% (72.6-94.8) and specificity 90% (55.5-98.3)]. The best threshold for cortisol percentage (30%) increment gave inferior results [sensitivity 61% (45.5-75.6) and specificity 70% (34.8-93.0)]. For the HDDST, the point on the ROC curve closest to 1 corresponded to a value of cortisol decrease from the baseline of 50%[sensitivity 77% (62.7-88.5), specificity 60% (26.4-87.6)]. The area under the ROC curve of the ACTH percentage increment after CRH was significantly greater than the area under the diagonal [0.9 (0.7-1.0), P= 0.0001]. Conversely, the area under the cortisol percentage decrement after dexamethasone was not different from that obtained by chance [0.7 (0.5-0.9), P= ns]. The area under the ROC curve of CRH is significantly greater than that of overnight HDDST (P = 0.03). A correct diagnosis has been achieved by the CRH test in 86.5% of cases and by the HDDST in 73% (P = 0.06). The combination of both tests has given a correct diagnosis in a significantly lower percentage of cases than the CRH test alone (69%, P= 0.04). The bilateral inferior petrosal sinus sampling (BIPSS) has been performed in 29 patients (24 CD, five EAS) who had negative imaging and/or discordant results of the noninvasive tests. Considering the criterion of a central to peripheral ACTH ratio > 3 after CRH stimulation, a correct diagnosis was achieved in all cases.",
            "output": [
                "Is the corticotrophin-releasing hormone test the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing 's syndrome?"
            ]
        },
        {
            "id": "task847-3a2a41289b544768bc8a5050a72ff8bb",
            "input": "Intrathecal adenosine is antinociceptive under conditions of central sensitization, but not in response to acute stimuli in normals. The reasons for this selective circumstance of action remain unclear, but some evidence links adenosine's antinociceptive effects to release of norepinephrine by terminals in the spinal cord. The purpose of this study was to test whether spinal adenosine induces norepinephrine release selectively in settings of hypersensitivity.\", 'Rats randomly assigned to spinal nerve ligation, sham operation, or no operation were anesthetized. A microdialysis fiber was implanted in the spinal cord dorsal horn at the L5-L6 level and perfused with artificial cerebrospinal fluid. After washout and a baseline sample period, adenosine at various concentrations was infused through the fiber for 150 min, and samples were collected every 15 min.', \"In ligated, but not in sham or normal animals, adenosine perfusion increased norepinephrine in spinal cord microdialysates in a concentration-dependent manner. The effects of adenosine plateaued after 75 min and remained stable until the end of the experiment. Intravenous injection of selective adenosine A1 and A2 receptor antagonists revealed that adenosine's effect on spinal norepinephrine release was A1 receptor mediated.",
            "output": [
                "Does intraspinal adenosine induce spinal cord norepinephrine release in spinal nerve-ligated rats but not in normal or sham controls?"
            ]
        },
        {
            "id": "task847-6cfaa3eb216c445b8d491098b13e193e",
            "input": "The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control.', 'Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia.', 'One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg).",
            "output": [
                "Are postoperative morphine use and hyperalgesia reduced by preoperative but not intraoperative epidural analgesia : implications for preemptive analgesia and the prevention of central sensitization?"
            ]
        },
        {
            "id": "task847-63452a9f3a65421597d1f5ba40d1ad8b",
            "input": "Acute uterine cervical distension (UCD) forms the basis for obstetric and some gynecologic pain. Systemic morphine inhibits the visceromotor response to UCD in rats by an action in the central nervous system, but the effect of morphine is blocked by exposure to estrogen. The purpose of the present study was to determine whether this estrogen blockade of the action of morphine reflects a spinal mechanism.', 'Virgin Sprague-Dawley rats received estrogen or placebo treatment for 1 week after ovariectomy. Rats were then anesthetized, and the electromyographic response in the rectus abdominis muscle to UCD was recorded in the absence and presence of cumulative dosing with intrathecal morphine.', 'Estrogen treatment did not alter the stimulus- response relationship between UCD and reflex muscle contraction. Intrathecal morphine reduced the visceromotor reflex response to UCD in a dose-dependent manner that was unaffected by estrogen treatment.",
            "output": [
                "Does intrathecal morphine reduce the visceromotor response to acute uterine cervical distension in an estrogen-independent manner?"
            ]
        },
        {
            "id": "task847-567eefad43454189a0b5ce8831f19b09",
            "input": "To map and compare the right atrium in patients with AF to those with atrioventricular nodal reentrant tachycardias (AVNRT, as control group) and to investigate the anatomical and electrophysiological abnormality of the right atrium in AF.', 'The anatomy and electrophysiology of right atrium and cavotricuspid isthmus were evaluated in 20 patients with AF (16 M/4 F, mean age 55.9 +/- 10.68 years) and 26 patients with AVNRT (9 M/17 F, mean age 47.50 +/- 19.56 years) during coronary sinus pacing at 600 ms prior to ablation with electro-anatomical mapping system. Right atrial volume (RAV), the length and width of cavotricuspid isthmus (IsL, IsW), unipolar and bipolar voltage in the right atrium (UniV-RA, BiV-RA) were measured and compared between patients with AF and those with AVNRT.', 'RAV, IsL, IsW, UniV-RA, and BiV-RA were 143.22 +/- 40.72 vs 104.35 +/- 21.06 ml, 39.31 +/- 8.10 vs 32.42 +/- 9.77 mm, 30.54 +/- 7.48 vs 23.15 +/- 6.61 mm, 1.96 +/- 1.24 vs 1.53 +/- 0.91 mv and 1.47 +/- 1.47 vs 1.29 +/- 1.12 mv in AF and AVNRT respectively.",
            "output": [
                "Is electro-anatomic mapping of the right atrium : anatomic abnormality an important substrate?"
            ]
        },
        {
            "id": "task847-88e0f6d7817b4876a4ebab4ae2fc8e90",
            "input": "To explore adolescent girls' personal experience with an infant simulator that had to be cared for over a period of 1 to 2 weeks.\", \"This qualitative study employed the phenomenological approach and utilized Colaizzi's method of analysis. Participants were nine adolescent high school girls who were interviewed and audiotaped. Interview data were coded using NUD*IST 4 software.\", 'Three themes emerged from the data. They were (1) a parenting journey incorporating intellectual, emotive, and physical faculties; (2) recognizing the illusionary nature of previously held ideas about parenting an infant; and (3) offering counsel based on the BTIO experience.",
            "output": [
                "Do adolescent girls ' personal experience with Baby Think It Over infant simulator?"
            ]
        },
        {
            "id": "task847-d93f79d4ee4a4d29bfd50e2552d77dfc",
            "input": "To investigate the surgical techniques and speech performance of multichannel auditory brainstem implant (ABI) in patients with bilateral acoustic neuromas (neurofibromatosis type 2).', 'The nucleus 21 channel auditory brainstem implant was implanted into the lateral recess of the fourth ventricle through the translabyrinthine approach in 7 patients after removal of the tumor. The accurate placement of electrode array was ensured by the electromyogram monitoring of the 7th and 9th nerves and the electrically evoked auditory brainstem responses (EABR). Initial switch-on occurred six weeks postoperatively. Speech evaluation was performed every 3 months for the first year and annually thereafter.', 'During the surgery, the lateral recess could be found and the typical EABR could be recorded in 6 cases. They later reported a significant benefit from the device. Two of the cases have achieved functional open-set speech understanding. In contrast, one patient with no EABR because of difficulty of the anatomic location during the surgery had no sensations postoperatively.",
            "output": [
                "Do [ Clinical application of the multichannel auditory brainstem implant ]?"
            ]
        },
        {
            "id": "task847-8513032969824c0cb6bbf14f70b50f58",
            "input": "Among factors that may affect the potency of botulinum toxin A (Botox), it is said that foam, together with bubbles, may cause surface denaturation of the toxin.', 'To determine whether the muscle relaxation effect of Botox is preserved and has the same duration when it is reconstituted in the presence of foam.', 'Six female volunteers, aged 42 to 56 years old, were treated for glabellar and periocular wrinkles. Each half of the face was treated with 16 U of Botox divided in four sites: three at the lateral orbital area and one at the medial brow, in the glabellar region. The right side received Botox gently reconstituted with saline to avoid foaming formation. The left side of the face was treated with Botox that was rapidly reconstituted in order to achieve as many bubbles as possible, even with shaking. Blinded observers compared pretreatment and posttreatment photographs and answered assessment-related questions. The results were analyzed clinically and statistically.', 'There was no difference in muscle paralysis between treated sides in all patients, neither in early (15 days) nor late (4 months) follow-up evaluations.",
            "output": [
                "Does foam during reconstitution affect the potency of botulinum toxin type A?"
            ]
        },
        {
            "id": "task847-dbf6c46bf9da4d84a9a5c0271a881219",
            "input": "BTX-A is the standard treatment for glabellar furrows. However, some individuals have resting glabellar rhytides that are sufficiently deep that they respond poorly to BTX-A alone.', 'To compare the efficacy of BTX-A combined with intradermal Hylan B with the efficacy of BTX-A alone in individuals with moderate to severe glabellar rhytides.', 'This was a retrospective study of 16 subjects with moderate to severe glabellar rhytides. Their response to Hylan B plus BTX-A was compared clinically and photographically to their response to BTX-A alone.', 'All subjects had moderate or severe glabellar rhytides at rest before treatment. After BTX-A alone, none (0%) had achieved no or mild rhytides. After BTX-A and Hylan B injection, only 1 of 16 (6%) had moderate glabellar rhytides, with the remainder (94%) being mild.",
            "output": [
                "Do deep resting glabellar rhytides respond to BTX-A and Hylan B?"
            ]
        },
        {
            "id": "task847-a14451f9fe094ba5bfb5c0e4fe5cd9b3",
            "input": "This study was conducted to measure the corneal thickness changes associated with wearing 30-day tisilfocon A (Dk = 163) and 6-day etafilcon A (Dk = 28) contact lenses. The probable cause of the outcomes is discussed.', 'Thirty subjects were fitted with Menicon Z rigid gas-permeable (RGP) contact lenses and a control group (n = 30) was fitted with ACUVUE hydrogel lenses, at two study sites. After a 2-week period of daily wear, subjects began prolonged wear. Measurements were performed at the dispensing visit, and then at the 2-week daily wear, the 1-week, 6-month, and 12-month extended- and continuous-wear visits.', 'Repeated measures analysis of covariance was performed on mean corneal thickness. There was a significant increase in corneal thickness in the hydrogel lens extended-wear group compared to the RGP group (P = 0.03). The mean corneal thickness in the ACUVUE group was 2.58% higher at the 2-week daily wear visit, 2.38% higher at the 1-week extended-wear visit, 2.96% higher at the 6-month, and 2.97% higher at the 1-year visit compared to the RGP continuous-wear patients.",
            "output": [
                "Does corneal thickness result in the Menicon Z 30-day continuous wear and ACUVUE 7-day extended-wear contact lens clinical trial?"
            ]
        },
        {
            "id": "task847-00ded82e02cd46cc89b416488bf94cf7",
            "input": "The hypothesis that in normotensive offspring of hypertensive parents exercise training could influence the systemic release of endothelin (ET)-1 during a provocative testing protocol was tested.', 'The provocative handgrip test was performed in four groups of healthy young age-matched males: offspring of hypertensive parents following a regular swimming exercise regimen (group A, n = 14); offspring of hypertensive parents and leading a sedentary lifestyle (group B, n = 11); normal volunteers with no family history of hypertension: sedentary (group C, n = 10), and following a regular swimming regimen (group D, n = 10). The plasma ET-1 was measured at baseline, after 4 min of handgrip exercise at 50% maximal capacity and following 2 (R2) and 10 (R10) min of recovery from handgrip.', 'ET-1 plasma levels, within the normal range in all groups at baseline (group A 0.94 +/- 0.32 pg/ml, group B 0.84 +/- 0.26 pg/ml, group C 0.78 +/- 0.35 pg/ml, group D 0.85 +/- 0.26, p = NS) showed a progressive and significant increase in group B during and after handgrip exercise (peak handgrip 1.08 +/- 0.5 pg/ml, p = NS; R2 1.35 +/- 0.36 pg/ml, p < 0.05; R10 2.76 +/- 0.75 pg/ml, p < 0.01). Significant differences were found at R2 and R10 when the ET-1 levels measured in group B were compared to those observed in group A, group C and group D. Multivariate analysis demonstrated that the serum levels of ET-1 significantly contributed to predict handgrip-induced changes when the diastolic blood pressure was the dependent variable.",
            "output": [
                "Does exercise training counteract the abnormal release of plasma endothelin-1 in normal subjects at risk for hypertension?"
            ]
        },
        {
            "id": "task847-071f2d4a1efe4803815d4b6f5881689f",
            "input": "The aim of this study was to compare the clinical characteristics of patients enrolled in randomized clinical trials on congestive heart failure treatment with those of real-world patients encountered in daily clinical practice.', 'We searched the Cochrane review methodology, Medline and SilverPlatter databases to obtain the clinical characteristics of both patients enrolled in therapeutic clinical trials and real-world patients with heart failure. We selected 27 clinical trials, and 8 prospective epidemiological studies or registries published between 1987 and 2001 which enrolled 53,859 and 18,207 patients, respectively.', 'On average, compared to real-world heart failure patients, patients enrolled in clinical trials were younger (63 +/- 10 vs 75 +/- 11 years respectively, p < 0.0001), and more likely to be male (72 vs 54% respectively, p < 0.0001). Clinical trial patients showed a lower ejection fraction (26 +/- 7 vs 38 +/- 15% respectively, p < 0.0001) but a lower prevalence of NYHA functional class III-IV (62 vs 75% respectively, p < 0.0001) than real-world patients. In clinical trial patients, the prevalence of ischemic heart disease (67 vs 42% respectively, p < 0.0001) and a history of previous myocardial infarction (62 vs 42% respectively, p < 0.0001) were higher than in real-world patients. Conversely, the prevalence of chronic atrial fibrillation (12 vs 31% respectively, p < 0.0001) and of diabetes (22 vs 24% respectively, p < 0.02) was lower in trial patients than in real-world patients.",
            "output": [
                "Are patients with chronic heart failure encountered in daily clinical practice different from the `` typical '' patient enrolled in therapeutic trials?"
            ]
        },
        {
            "id": "task847-f74a3b411595414d999e2ac58892c0c1",
            "input": "To determine the clinical activity and the toxicity profile of the topoisomerase-I inhibitor, topotecan, in women with recurrent or advanced endometrial carcinoma.', 'A prospective, phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG). Patients had histologically confirmed advanced or recurrent endometrial carcinoma, measurable disease, no prior cytotoxic therapy, an ECOG performance status of 0 to 2, and evidence of disease progression while on progestins or after radiation therapy. Topotecan was administered at 1.5 mg/m(2) (or 1.2 mg/m(2) for patients with prior pelvic radiation) intravenously daily for 5 days every 3 weeks.', 'A total of 44 patients were enrolled; 42 were eligible. The study was suspended because of unexpected toxicities, primarily sepsis and bleeding. After toxicity review, the study was reopened using lower doses of topotecan (1.0 mg/m(2) or 0.8 mg/m(2) for patients with prior radiation therapy). In addition, prophylactic use of growth factors was allowed after the first cycle, and patients with performance status of 2 were excluded. The major toxicities were hematologic and gastrointestinal. Among the 40 assessable patients, there were three (7.5%) complete responders and five partial responders (12.5%), for an overall response rate of 20%. The median duration of response was 8.0 months and of overall survival was 6.5 months.",
            "output": [
                "Is topotecan an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma : Eastern Cooperative Oncology Group Study E3E93?"
            ]
        },
        {
            "id": "task847-a813d391c7064581a061cd65d345d057",
            "input": "Peptone meal-stimulated gastric acid output is considered to be a reliable means to evaluate drug-mediated inhibition of stimulated gastric acid output, an important measure of the efficacy of the agents--such as proton pump inhibitors--used to treat acid-related disorders.', 'To compare the initial and overall inhibitory effects on peptone meal-stimulated gastric acid secretion of rabeprazole and omeprazole, 20 mg, in Helicobacter pylori-negative subjects on the first and eighth days of treatment.', 'Healthy volunteers (n = 27) were randomized in a single-centre, double-blind, double-dummy, 2 x 2 cross-over study. Subjects received an oral dose of rabeprazole or omeprazole, 20 mg once daily, for 8 days. After a 2-4-week washout period, subjects were crossed over to receive the other medication for 8 days. Peptone meal-stimulated gastric acid secretion was measured at hours 11 and 23 at baseline and on days 1 and 8 of treatment.', 'On days 1 and 8, rabeprazole demonstrated a significantly greater inhibition of peptone meal-stimulated gastric acid secretion compared with omeprazole at all time points (P < 0.03). Median values of steady-state inhibition on day 1 were statistically significant at hour 23 (rabeprazole 100% vs. omeprazole 74%, P < 0.02).",
            "output": [
                "Is rabeprazole superior to omeprazole for the inhibition of peptone meal-stimulated gastric acid secretion in Helicobacter pylori-negative subjects?"
            ]
        },
        {
            "id": "task847-8468b22ed69c406abebb0bf5fd89f0a9",
            "input": "Circulating adrenomedullin (ADM), a potent vasorelaxing and natriuretic peptide involved in cardiovascular homeostasis, is increased after cardiac and renal transplantation. ADM is also implicated in hemodynamic abnormalities during liver cirrhosis, but whether ADM is increased late after liver transplantation is unknown.', 'A total of 18 subjects--10 liver-transplant patients (Ltx) and 8 healthy subjects--were enrolled in the study.', 'After a 15-min rest period in supine position, heart rate and systemic blood pressure were determined in all subjects. Then, venous blood samples were obtained in order to simultaneously determine the cyclosporine through levels, the biological (cyclosporine, renal and hepatic functions) and hormonal (ADM and atrial natriuretic peptide (ANP)) characteristics of the Ltx.', 'ADM (27.2+/-4.1 vs. 53.8+/-6.9 pmol/l, P=0.02), and ANP (5.9+/-0.9 vs. 12.8+/-1.4 pmol/l, P=0.001) were significantly increased in late, stable Ltx (35.4+/-9.6 months after transplantation). Furthermore, increased ADM correlated positively with elevated creatinine (r=0.76, P=0.01) and ANP (r=0.64, P=0.04) after liver transplantation.",
            "output": [
                "Is circulating adrenomedullin increased in relation with increased creatinine and atrial natriuretic peptide in liver-transplant recipients?"
            ]
        },
        {
            "id": "task847-be4a59e5ea83420188a15084dae417ee",
            "input": "Individuals with histories of smoking in first-degree relatives are significantly more likely to be persistent smokers themselves. The mechanisms underlying this relationship are unknown. Considerable research has demonstrated that smokers display heightened levels of cigarette craving after being exposed to stressful situations, and the magnitude of these craving responses is thought to be predictive of later cessation failure. Based on this research, we tested experimentally the hypothesis that smokers with two or more first-degree relatives who smoked (FH+) would exhibit stronger craving reactions following stressful stimuli than smokers without such family histories (FH-).', 'We recruited 83 smokers by advertisement (mean age = 41.2 years, 57% female, 41% completed some college, 59% African American).', 'The study was conducted in an interview room in an urban medical center.', 'Participants were exposed to a neutral situation (changing a lightbulb) and a stressful situation (dental work) using script-guided imagery.', 'Participants completed background measures of demographics, distress and smoking behavior. In addition, participants completed cigarette craving and anxiety questionnaires immediately before and after each condition.', 'Supporting the study hypothesis, FH+ smokers (n = 39) selectively displayed stronger craving reactions to dental imagery (P < 0.03) than did FH- smokers (n = 44).",
            "output": [
                "Does a family history of smoking predict heightened levels of stress-induced cigarette craving?"
            ]
        },
        {
            "id": "task847-79be3de606af42eca60abe6a60b5be60",
            "input": "We sought to describe the degree of long-term left ventricular (LV) remodeling after acute transmural myocardial infarction with preserved LV systolic function, and to evaluate whether Doppler echocardiographic parameters in the early phase could predict this process.', 'A total of 60 patients without heart failure and with LV ejection fraction > or = 0.40 (mean 0.48 +/- 0.054), were followed up with Doppler echocardiographic examinations at baseline, 3 months, and 1 and 2 years.', 'There was a significant increase in LV end-diastolic volume index of 7% (P =.006) and LV end-systolic volume index of 8% (P =.03), and no change in ejection fraction. This remodeling was confined to 7 patients (12%) with a significant increase in LV end-diastolic volume index above 20 mL/m(2). There was also a significant increase in the deceleration time of both the early mitral filling wave (Delta early mitral filling wave = 58 milliseconds, P <.0005) and the diastolic forward component of pulmonary venous flow (Delta diastolic forward component of pulmonary venous flow = 61 milliseconds, P <.0005), and a shift in filling pattern with increasing prevalence of abnormal relaxation. Changes in end-diastolic volume index were predicted by baseline early mitral filling wave less than 100 milliseconds, but the most powerful predictors of 2-year remodeling were volume changes at 3 months.",
            "output": [
                "Are early changes in left ventricular volume and function predictors for long-term remodeling in patients with acute transmural myocardial infarction and preserved systolic function?"
            ]
        },
        {
            "id": "task847-1739e88688c34346a539eb0940bf5ade",
            "input": "The purpose of this study was to evaluate the clinical efficacy of endosonographically guided transrectal aspiration and drainage by plastic stent of deep pelvic abscesses, using a therapeutic echo endoscope device.', 'Between September 2000 and June 2001, 12 patients (nine men, three women, mean age 67 years) were treated for a perirectal or a pelvic abscess using an endoscopic ultrasound (EUS) technique. The drainage of these fluid collections was performed under EUS guidance, using therapeutic EUS scopes with a large working channel.', 'No major complication occurred during this study. Transrectal stent insertion succeeded in nine patients. In three patients, only aspiration was possible. Among the nine patients in whom a stent was successfully introduced into the fluid collection, complete drainage without relapse was achieved in eight patients (mean follow-up 10.6 months, range 6-14 months). The stent was removed endoscopically after 3 to 6 months. Drainage was incomplete in one patient (with a large abscess, diameter > 8 cm), who subsequently underwent surgical drainage. However, two out of the three patients in whom aspiration alone was performed developed a recurrence of the abscess and required surgical treatment.",
            "output": [
                "Do drainage of deep pelvic abscesses using therapeutic echo endoscopy?"
            ]
        },
        {
            "id": "task847-9a60015924c0427d9fb2940a62e57b31",
            "input": "We investigated the relationship of bladder mass to responses to electrical field stimulation and adrenergic agonists in diabetic rat bladders.', 'Longitudinal strips were removed from the ventral and dorsal detrusor of age matched control, 2-month diabetic and sucrose drinking rats. Contractile responses to electrical field stimulation, KCl and phenylephrine, and relaxation in response to norepinephrine and isoproterenol were measured.', 'Bladders from sucrose drinking and diabetic rats weighed significantly more than those of controls. Diabetic rats were divided into 2 groups with the bladder weighing less than or greater than 265 mg. Strips from small diabetic bladders were generally more responsive to field stimulation and norepinephrine than those from control or sucrose drinking rats. Conversely decreased function was especially apparent in dorsal strips from large diabetic bladders. Ventral strips were significantly more sensitive to the relaxant actions of norepinephrine and isoproterenol than dorsal strips.",
            "output": [
                "Does functional response of bladder strips from streptozotocin diabetic rats depend on bladder mass?"
            ]
        },
        {
            "id": "task847-d11eb7ac2f524f76900899943132e6e7",
            "input": "The proliferation of mural epithelial cells is a major cause of progressive cyst enlargement in autosomal-dominant polycystic kidney disease (ADPKD). Adenosine 3', 5' cyclic monophosphate (cAMP) stimulates the proliferation of cells from ADPKD cysts, but not cells from normal human kidney cortex (HKC), through the activation of protein kinase A (PKA), mitogen-activated protein kinase kinase (MEK), and extracellular signal-regulated kinase (ERK/MAPK). In the current study, we examined the signaling pathway between PKA and MEK in ADPKD and HKC cells.\", 'Primary cultures of human ADPKD and HKC cells were prepared from nephrectomy specimens. We determined the effects of cAMP and epidermal growth factor (EGF) on the activation of ERK, B-Raf and Raf-1 in ADPKD and HKC cells by immune kinase assay and Western blot.', '8-Br-cAMP increased phosphorylated ERK (2.7- +/- 0.6-fold, N = 7), and B-Raf kinase activity (3.6- +/- 1.1-fold, N = 5) in cells from ADPKD kidneys; levels of phosphorylated Raf-1 were not changed. Inhibition of PKA by H89 strikingly decreased cAMP-stimulated phosphorylation of ERK and B-Raf, and MAPK inhibition by PD98059 blocked the effect of the nucleotide to activate ERK. By contrast, in HKC cells 8-Br-cAMP did not activate B-Raf and ERK. EGF stimulated the phosphorylation of ERK and Raf-1 in both ADPKD and HKC cells, but had no effect on B-Raf. 8-Br-cAMP and EGF conjointly increased ERK activation above that of either agonist alone in ADPKD cells, and this combined effect was abolished by PD98059, indicating that ERK was activated by EGF- and cAMP-responsive cascades that converge at MAPK.",
            "output": [
                "Does cyclic AMP activate B-Raf and ERK in cyst epithelial cells from autosomal-dominant polycystic kidneys?"
            ]
        },
        {
            "id": "task847-f2dae79219644beb82f4fcd2b8395baf",
            "input": "Residual paralysis increases the risk of pulmonary complications but is difficult to detect. To test the hypothesis that accelerometry predicts effects of residual paralysis on pulmonary and upper airway function, the authors related tests of pulmonary and pharyngeal function to accelerometry of adductor pollicis muscle in 12 partially paralyzed volunteers.', 'Rocuronium (0.01 mg/kg + 2-10 microg x kg-1 x min-1) was administered to maintain train-of-four (TOF) ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min. The authors evaluated pharyngeal and facial muscle functions during steady state relaxation and performed spirometric measurements every 5 min until recovery. Upper airway obstruction was defined as a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of greater than 1. The TOF ratio associated with \"acceptable\" pulmonary recovery (forced vital capacity and forced inspiratory volume in 1 s of > or =90% of baseline) was calculated using a linear regression model.', 'At peak blockade (TOF ratio 0.5 +/- 0.16), forced inspiratory flow was impaired (53 +/- 19%) to a greater degree than forced expiratory flow (75 +/- 20%) with a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of 1.18 +/- 0.6. Upper airway obstruction, observed in 8 of 12 volunteers, paralleled an impaired ability to swallow reported by 10 of 12 volunteers. In contrast, all volunteers except one could sustain a head lift for more than 5 s. The authors calculated that a mean TOF ratio of 0.56 (95% confidence interval, 0.22-0.71) predicts \"acceptable\" recovery of forced vital capacity, whereas forced inspiratory volume in 1 s was impaired until a TOF ratio of 0.95 (0.82-1.18) was reached. A 100% recovery of TOF ratio predicts an acceptable recovery of forced vital capacity, forced inspiratory volume in 1 s, and mean ratio of expiratory and inspiratory flow at 50% of vital capacity in 93%, 73%, and 88% of measurements (calculated negative predictive values), respectively.",
            "output": [
                "Does accelerometry of adductor pollicis muscle predict recovery of respiratory function from neuromuscular blockade?"
            ]
        },
        {
            "id": "task847-be34634d9cb340cd9638b1d5499bf7d5",
            "input": "Troponin I (TnI) and myosin light chain 2 (MLC2) are important myofibrillar proteins involved in the regulation of myofilament calcium (Ca2+) sensitivity and cardiac inotropy. The objectives of this study were to determine the role of protein kinase C (PKC) in mediating propofol-induced changes in actomyosin adenosine triphosphatase activity in cardiac myofibrils and to examine the extent to which propofol alters the phosphorylation of TnI and MLC2 in cardiomyocytes.', 'Freshly isolated adult rat ventricular myocytes were used for the study. Cardiac myofibrils were extracted for assessment of actomyosin adenosine triphosphatase activity and phosphorylation of TnI and MLC2. Western blot analysis for PKC-alpha was performed on cardiomyocyte subcellular fractions. Simultaneous measurement of intracellular free Ca2+ concentration ([Ca2+](i)) and myocyte shortening was assessed using fura-2 and video edge detection, respectively.', 'Propofol (30 microM) reduced the Ca2+ concentration required for activation of actomyosin adenosine triphosphatase activity, and this effect was abolished by bisindolylmaleimide I. In addition, propofol stimulated dose-dependent phosphorylation of TnI and MLC2. PKC activation with phorbol myristic acetate also stimulated an increase in phosphorylation of TnI and MLC2. The actions of propofol and phorbol myristic acetate together on phosphorylation of TnI and MLC2 were not additive. PKC inhibition with bisindolylmaleimide I attenuated phorbol myristic acetate- and propofol-induced phosphorylation of TnI and MLC2. Propofol stimulated translocation of PKC-alpha from cytosolic to membrane fraction. Propofol caused a shift in the extracellular Ca2+-shortening relationship, and this effect was abolished by bisindolylmaleimide I.",
            "output": [
                "Does propofol increase phosphorylation of troponin I and myosin light chain 2 via protein kinase C activation in cardiomyocytes?"
            ]
        },
        {
            "id": "task847-de157bbb708949e0b232814bbe10d008",
            "input": "It is well documented that oxidized low-density lipoproteins (LDLs) can stimulate human vascular endothelial cells to produce monocyte chemoattractant protein-1 (MCP-1). Vitamin C is known to be an important antioxidant for vasodilatation. The purpose of this study was to determine whether pretreatment with vitamin C could protect against oxidized-LDL-induced expression of MCP-1 in cultured human umbilical vein endothelial cells (HUVECs).', 'Cultured HUVECs were used for desired experiments before passage 4. Lysophosphatidylcholine (lysoPC), an oxidized component of LDL, was designated as the stimulator for MCP-1 synthesis from cultured HUVECs. MCP-1 concentrations in the cultured media were determined by enzyme-linked immunosorbent assay. MCP-1 RNA was evaluated by a semi-quantitative reverse transcriptase-polymerase chain reaction.', 'HUVECs secreted MCP-1 within 30 minutes after exposure to 50 microM lysoPC. Compared with samples treated with lysoPC alone, pretreatment with vitamin C in concentrations of 50, 100, 150, and 200 microM, reduced levels of MCP-1 in the culture medium by 44%, 51%, 60%, and 67%, respectively, while levels of MCP-1 mRNA decreased by 15%, 18%, 80%, and 82%, respectively.",
            "output": [
                "Does vitamin C protect against lysophosphatidylcholine-induced expression of monocyte chemoattractant protein-1 in cultured human umbilical vein endothelial cells?"
            ]
        },
        {
            "id": "task847-782561d775c344e89456363a9ef1d2d3",
            "input": "To evaluate the diagnostic significance of CT scan in the localization of the stricture in the upper airway in patients with obstructive sleep apnea syndrome (OSAS).', \"Fifty-four patients with OSAS were included in this study. CT scan evaluated the upper airway from the roof of nasopharynx to the glottis using a Phlips Tomoscan AV Expander E1 spiral scanner. The areas and the dimensions of palate, uvula, lingua and epiglottis region, as well as the thickness of retropharyngeal and lateral pharyngeal tissue was evaluated. The reference values had been set-up in 225 normal adult upper airways CT scan, some patients' results were compared with the CT scan results during apnea.\", 'There were no any upper airway stricture in 12 patients with OSAS, and there were one or more upper airway stricture sites in other 42 patients. Twenty-four patients had only one stricture site. Fourteen patients had 2 adjacent stricture sites. One patient had three stricture sites. Three patients had 4 upper airway strictures. There was a good concordance between the results of CT scans during awakening and sleeping in 14 patients.",
            "output": [
                "Do [ Localization of upper airway stricture in patients with obstructive sleep apnea syndrome by CT scan ]?"
            ]
        },
        {
            "id": "task847-63e51388e62f4433880e0ba9167e8ec6",
            "input": "Postictal inhibition (PI) is a decrease in excitability that follows an epileptic seizure and decreases probability of new seizure occurrence. PI may involve both increased inhibition and persisting elevated excitation. Our experiments tested whether shorter trains of weak stimuli are able to unmask this residual increase of excitability during the PI.', 'Four epileptic afterdischarges (ADs) were evoked by intense electrical stimulation (20 s, 8 Hz, current intensity at 5x threshold) of the neocortex in two groups (A, B) of Wistar rats. Before the first AD and during the 10-min interictal period, 8-Hz trains of four weak pulses (half of the intensity used for the AD triggering; 4P) were applied every 20 s in group B and a single pulse with similar parameters in group A.', 'The number of interictal epileptiform events evoked by 4P in the group B was significantly higher than that in the group A (evoked by single pulses) except after the second AD. Epileptic events were triggered by 4P also immediately after the AD termination.",
            "output": [
                "Do short bursts of weak pulses break postictal inhibition in the neocortex of Wistar rats?"
            ]
        },
        {
            "id": "task847-ace743df771643649fab25746c9714d6",
            "input": "To determine whether repeated seizures contribute to hippocampal sclerosis, we investigated whether cell loss in the (para) hippocampal region was related to the severity of chronic seizure activity in a rat model for temporal lobe epilepsy (TLE).', 'Chronic epilepsy developed after status epilepticus (SE) that was electrically induced 3-5 months before. The presence of neuronal damage was assessed by using Fluoro-Jade and dUTP nick end-labeling (TUNEL) of brain sections counterstained with Nissl.', 'We found a negative correlation between the numbers of surviving hilar cells and the duration of the SE (r = -0.66; p < 0.01). In the chronic phase, we could discriminate between rats with occasional seizures (0.15 +/- 0.05 seizures per day) without progression and rats with progressive seizure activity (8.9 +/- 2.8 seizures/day). In both groups, the number of TUNEL-positive cells in parahippocampal regions was similar and higher than in controls. In the hippocampal formation, this was not significantly different from controls. Fluoro-Jade staining showed essentially the same pattern at 1 week and no positive neurons in chronic epileptic rats.",
            "output": [
                "Is neuronal cell death in a rat model for mesial temporal lobe epilepsy induced by the initial status epilepticus and not by later repeated spontaneous seizures?"
            ]
        },
        {
            "id": "task847-321ed6ed2203446f872dc30413e6fdd0",
            "input": "Left ventricular hypertrophy (LVH) is common in patients with autosomal dominant polycystic kidney disease (ADPKD). Although insulin resistance contributes to cardiac hypertrophy, the relationship between insulin resistance and LVH in patients with ADPKD has not been previously studied.', 'We performed M-mode and color Doppler echocardiography on 176 family members (106 patients and 70 healthy relatives) from 16 families with polycystic kidney disease type 1 (PKD1). Left ventricular mass index (LVMI) was calculated using the Penn equation and corrected for body surface area. Fasting insulin and glucose concentrations were measured and insulin resistance was evaluated by means of the homeostasis model assessment.', 'In multivariate regression analysis, insulin resistance was significantly associated with LVMI in healthy relatives (P < 0.01) and patients with PKD1 (P < 0.05) independent of age, weight, systolic blood pressure, and albuminuria.",
            "output": [
                "Is insulin resistance related to left ventricular hypertrophy in patients with polycystic kidney disease type 1?"
            ]
        },
        {
            "id": "task847-1bdcf18e622444f4a1b1fd5cc02278e3",
            "input": "To find sensitive and specific laboratory examination items for early diagnosing and monitoring liver transplantation reject reaction.', 'Randomly investigate 41 liver transplantation patients, among them there were 16 patients with reject reaction (including 12 with acute rejection, 4 with chronic rejection). Plasma soluble thrombomodulin (STM) and von Willebrand factor (vWF) levels were measured before operation and every other day after operation.', 'Plasma STM level increased significantly after operation, two days before rejection and after acute rejection (5.58 ng/ml +/- 0.42 ng/ml, 5.93 ng/ml +/- 0.45 ng/ml, and 7.88 ng/ml +/- 0.29 ng/ml, respectively), so did vWF level (101.2% +/- 4.68%, 104.3% +/- 5.78%, and 127.7% +/- 5.74%, respectively). STM level was much higher in acute rejection than that in chronic rejection (7.88 ng/ml +/- 0.29 ng/ml vs. 6.35 ng/ml +/- 0.54 ng/ml, t = 2.46, P < 0.05), in no reaction group after impacting therapy than in effective group (8.30 ng/ml +/- 0.19 ng/ml vs. 3.82 ng/ml +/- 0.22 ng/ml, t = 12.98, P < 0.01), and in dead group after treatment than in living group (7.98 ng/ml +/- 0.18 ng/ml vs. 6.51 ng/ml +/- 0.41 ng/ml, t = 3.39, P < 0.01).",
            "output": [
                "Do [ Values of soluble thrombomodulin and von Willebrand factor judging reject reaction in liver transplantation ]?"
            ]
        },
        {
            "id": "task847-23ac0fe76aba4881b74775ade16953c0",
            "input": "Visceral obesity is shown to be a predictor of morbidity and mortality. We evaluated the association of measurements of generalized adiposity and visceral fat area (VFA), with abnormalities of metabolic syndrome (MS).', 'Seventy-six women (47.9 +/- 9.2 years) with BMI of 38.7 +/- 5.4 kg/m(2) underwent anthropometric measurements, laboratory procedures, bioeletrical impedance, and abdominal computed tomography (CT) scan. Diagnosis of MS was based on the presence of abdominal obesity and at least two of the following components: hypertension, dyslipidemia, and glucose intolerance and/or hyperinsulinemia.', 'BMI was correlated with both components of adipose tissue--subcutaneous (r = 0.66, P < 0.01) and VFA (r = 0.33, P < 0.02)--and leptin levels (r = 0.38, P < 0.01). In contrast, VFA was correlated with 2-h glucose and insulin levels (r = 0.32 and 0.35, P < 0.05, respectively), triglyceride, HDL cholesterol, and uric acid (r = 0.33, -0.34 and 0.24, P < 0.05, respectively). Subjects with high VFA, matched for BMI, showed greater plasma glucose area under the curve (621 +/- 127 vs. 558 +/- 129 mg x h(-1) x dl(-1), P < 0.05), 2-h insulin (804 +/- 599 vs. 579 +/- 347 pmol/l, P < 0.05), and uric acid levels (0.33 +/- 0.07 vs. 0.26 +/- 0.06 mmol/l, P < 0.05) than subjects with low VFA. In logistic regression analysis, waist circumference, VFA, and 2-h insulin were identified as independent predictors of MS. Receiver operating characteristic curve analysis pointed out the values of 104 cm for waist circumference (58.1% specificity, 84.1% sensitivity), 158.5 cm(2) for VFA (78.1% specificity, 52.3% sensitivity), and 559.8 pmol/l for 2-h insulin (71.9% specificity, 69.8% sensitivity); the presence of at least two of the three variables resulted in a degree of concordance of 76%.",
            "output": [
                "Does two-hour insulin determination improve the ability of abdominal fat measurement to identify risk for the metabolic syndrome?"
            ]
        },
        {
            "id": "task847-8c83d978f6b34a35a02f6cd698c0cb57",
            "input": "To compare a simple meal plan emphasizing healthy food choices with a traditional exchange-based meal plan in reducing HbA(1c) levels in urban African Americans with type 2 diabetes.', 'A total of 648 patients with type 2 diabetes were randomized to receive instruction in either a healthy food choices meal plan (HFC) or an exchange-based meal plan (EXCH) to compare the impact on glycemic control, weight loss, serum lipids, and blood pressure at 6 months of follow-up. Dietary practices were assessed with food frequency questionnaires.', 'At presentation, the HFC and EXCH groups were comparable in age (52 years), sex (65% women), weight (94 kg), BMI (33.5), duration of diabetes (4.8 years), fasting plasma glucose (10.5 mmol/l), and HbA(1c) (9.4%). Improvements in glycemic control over 6 months were significant (P < 0.0001) but similar in both groups: HbA(1c) decreased from 9.7 to 7.8% with the HFC and from 9.6 to 7.7% with the EXCH. Improvements in HDL cholesterol and triglycerides were comparable in both groups, whereas other lipids and blood pressure were not altered. The HFC and EXCH groups exhibited similar improvement in dietary practices with respect to intake of fats and sugar sweetened foods. Among obese patients, average weight change, the percentage of patients losing weight, and the distribution of weight lost were comparable with the two approaches.",
            "output": [
                "Is a simple meal plan emphasizing healthy food choices as effective as an exchange-based meal plan for urban African Americans with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-fd87aa6db6c24a7da722b7a390b4fde6",
            "input": "To assess pregnancy outcome in women with anaemia during pregnancy.', 'The study design involved a retrospective chart review of all women registering for prenatal care in the area of Kuopio University Hospital between 1990 and 2000. A haemoglobin concentration below 100g/l was used as a cutoff for anaemia and affected women (N=597) were stratified by the trimester at which anaemia was diagnosed. Multiple regression analysis was used to compare obstetric outcomes in the study groups and in non-anaemic women (N=22,202).', 'The frequency of anaemia was 2.6%, with 0.3% occurring in the first trimester. After controlling for confounding factors, anaemia detected in the first trimester was associated with low-birth-weight infants (OR=3.14, 95% CI: 1.35-7.28) whereas the mid- and third-trimester anaemia groups showed no significantly different outcomes when compared with the non-anaemic women. First trimester anaemia was not significantly associated with small birth weight for gestational age (OR=0.98, 95% CI: 0.41-2.17) or with premature delivery <37 weeks (OR=1.80, 95% CI: 0.72-4.49).",
            "output": [
                "Is anaemia in the first but not in the second or third trimester a risk factor for low birth weight?"
            ]
        },
        {
            "id": "task847-1f3cfa2215564c1594ff0021b84e4053",
            "input": "To investigate the mechanism by which methylprednisolone protects the liver from hypoxia-induced injury.', 'Prospective control study using the isolated rat liver.', 'Animal research facility.', 'Male, fasted, pathogen-free Sprague-Dawley rats.', 'Low-flow hypoxia was produced by reducing afferent perfusate pressure from 10 to 2.5 cm H(2)O; isolated livers were portally perfused for 2 hrs.', \"We measured mitochondrial membrane potential and hydrogen peroxide production by imaging rhodamine 123 and 2'-7'-dichlorofluorescein fluorescence, respectively. Leakage of mitochondrial enzymes was also monitored by assaying mitochondrial aspartate aminotransferase activity in the outflow perfusate, and the radical-scavenging effect of methylprednisolone was assessed by measuring luminol-dependent hydrogen peroxide chemiluminescence. Apoptosis in liver cells was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling. Rhodamine 123 fluorescence was significantly diminished in the hypoxic liver, especially in the region of the terminal hepatic venules, which is indicative of membrane depolarization in the mitochondria in those areas. Hypoxia-induced mitochondrial dysfunction was indicated by leakage of aspartate aminotransferase into the outflow perfusate, and increased 2'-7'-dichlorofluorescein fluorescence indicated increased hydrogen peroxide levels, particularly in the midzone. Pretreatment with 30, 10, or 3 mg/kg of methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization and enzyme leakage, although hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected.",
            "output": [
                "Does methylprednisolone inhibit low-flow hypoxia-induced mitochondrial dysfunction in isolated perfused rat liver?"
            ]
        },
        {
            "id": "task847-be7db1f286d84c199f9985710bf69f98",
            "input": "The sphingomyelin pathway is an important intracellular mechanism in regulating cell growth. The first step in this pathway is catalysed by sphingomyelinases. Alkaline sphingomyelinase is specifically located in the intestinal tract. Markedly reduced alkaline sphingomyelinase activities have been found in sporadic colorectal tumours and in familial adenomatous polyposis adenomas. Since the adenomatous polyposis coli (APC) gene is mutated in about 80% of sporadic colorectal tumors, and familial adenomatous polyposis is the consequence of a germline mutation of the same gene, we examined whether low alkaline sphingomyelinase activity is linked to APC gene mutations.', 'Both germline and sporadic adenomatous polyposis coli gene mutations were studied. Alkaline, neutral, and acid sphingomyelinase activities were measured in the intestinal mucosa and content of multiple intestinal neoplasia mice, a murine model of familial adenomatous polyposis and compared to control mice. Alkaline sphingomyelinase activity was also measured in 11 human rectal tumors with APC gene mutation and compared with 9 control tumors without mutation.', 'Alkaline, neutral, and acid sphingomyelinase activities were present in the small intestine and colon in both mice types with no differences in hydrolytic capacity or distribution pattern. In sporadic rectal tumors similar alkaline sphingomyelinase activities were identified in tumors with somatic APC gene mutations as in samples without mutations. In the tumors without detectable APC mutations beta-catenin was analyzed, but no mutation was detected.",
            "output": [
                "Is reduction in alkaline sphingomyelinase in colorectal tumorigenesis related to the APC gene mutation?"
            ]
        },
        {
            "id": "task847-0c10fd06a575487eafd26fe55c7682f2",
            "input": "Apart from surgery, treatment of rectal cancer increasingly involves the use of (neo-)adjuvant strategies. To optimize the selection process for these therapy regimens, especially in the field of cellular and molecular biology, new prognostic factors additional to the established TNM system are being investigated.', 'Two groups of patients ( n=2x85) with rectal carcinoma curatively treated by surgery alone were studied retrospectively (median follow-up 6.1 years). To exclude the effect of the surgeon only patients free of locally recurrent disease were selected. Patient groups were matched for age, gender, UICC stage, and year of operation (1982-1991) and differed only in subsequent metachronous distant metastatic spread, i.e., the criterion to be studied. The factors investigated in uni- and multivariate analysis were angiogenesis, density of dendritic cells, grading, venous invasion, and lymphatic invasion.', 'Grading invariably proved to be the only significant prognostic factor. In univariate analysis the absence of venous invasion was also correlated significantly with increased disease-free survival.",
            "output": [
                "Are angiogenesis and dendritic cell density correlated with metachronous distant metastasis in curatively operated rectal cancer?"
            ]
        },
        {
            "id": "task847-d1aceebbddaa42a4a0b79c893a2a42e8",
            "input": "Cardiovascular device-centered infections are a major cause of hospital morbidity, mortality, and expense. Caused by opportunistic bacteria, this phenomenon is thought to arise because of a defect in neutrophil bacterial killing. We have shown that neutrophils that adhere to polystyrene remain viable, whereas neutrophils that adhere to the vascular biomaterials expanded polytetrafluoroethylene (ePTFE) and Dacron undergo a rapid nonapoptotic death. This study was designed to test the hypothesis that surface topography is a determinant of the nonapoptotic death response of neutrophils to biomaterials.', 'We took advantage of the ease with which a polystyrene surface can be manipulated to examine the effect of surface topography on neutrophil viability. Neutrophils were exposed to smooth or roughened polystyrene surfaces both in vivo and in vitro. Changes in cell membrane permeability and production of reactive oxygen species by individual cells were monitored with fluorescent dyes.', 'Host cells and isolated human neutrophils died rapidly after adhesion to roughened polystyrene. Neutrophils adherent to roughened surfaces produced more reactive oxygen intermediates than those adherent to smooth surfaces and were first to die. The cell death response precipitated by expanded polytetrafluoroethylene, Dacron, or the roughened surfaces was significantly reduced with treatment of the neutrophils with catalase, diphenylene iodonium, or the src kinase inhibitor PP2 before adhesion.",
            "output": [
                "Is neutrophil survival on biomaterials determined by surface topography?"
            ]
        },
        {
            "id": "task847-057b2fcf171c4d7a8ffae3168fd4ec84",
            "input": "To investigate patterns of detection and variables associated with early diagnosis of melanoma in a population at intermediate melanoma risk.', 'Survey.', 'Hospital and university centers belonging to the Italian Multidisciplinary Group on Melanoma.', 'Eight hundred sixteen patients who were consecutively diagnosed as having melanoma and treated at 11 participating centers.', \"Relationship between patterns of detection and patient's and physician's delay with melanoma thickness, assessed by multivariate analysis.\", \"A statistically significant association with early diagnosis was found for female sex (odds ratio [OR] for a lesion >1 mm in thickness, 0.70; 95% confidence interval [CI], 0.50-0.97), higher educational level (OR, 0.44; 95% CI, 0.24-0.79), residence in northern and central Italy (compared with southern Italy) (OR, 0.44; 95% CI, 0.30-0.65 and OR, 0.24; 95% CI, 0.15-0.37, respectively), and the habit of performing a skin self-examination (OR, 0.65; 95% CI, 0.45-0.93). When adjusted for all the previously mentioned variables, only melanoma detection made by a dermatologist, maybe incidentally, was associated with a statistically significant additional effect on early diagnosis (OR, 0.45; 95% CI, 0.28-0.73). No significant effect of anatomical site (trunk compared with other sites: OR, 0.83; 95% CI, 0.59-1.17), presence of atypical nevi (OR, 0.78; 95% CI, 0.52-1.17), and patient's delay (>3 months compared with < or =3 months: OR, 1.12; 95% CI, 0.78-1.60) was found.",
            "output": [
                "Are dermatologist detection and skin self-examination associated with thinner melanomas : results from a survey of the Italian Multidisciplinary Group on Melanoma?"
            ]
        },
        {
            "id": "task847-b453686bf3964350a0c9f40d87af508a",
            "input": "Prostate specific antigen (PSA) is a kallikrein family member with serine protease activity commonly used as a diagnostic marker for prostate cancer. We recently described anti-angiogenic properties of PSA [Fortier et al.: JNCI 91:1635-1640].', 'Two forms of PSA were cloned and expressed in Pichia pastoris: one, an intact PSA with an N-terminus of IVGGVS em leader; the second, an N-1 PSA variant. The recombinant proteins were tested for serine protease activity and for anti-angiogenic activity in vitro and in vivo.', 'The rate of substrate hydrolysis by the intact recombinant PSA was similar to that of PSA isolated and purified from human seminal plasma. In contrast, the N-1 PSA variant lacked serine protease activity. In an endothelial cell migration assay, the concentration that resulted in 50% inhibition (IC(50)) was: 0.5 microM for native PSA, 0.5 microM for intact recombinant protein, and 0.1 microM for the N-1 variant PSA. Both the intact recombinant and the N-1 recombinant PSA inhibited angiogenesis in vivo.",
            "output": [
                "Does recombinant prostate specific antigen inhibit angiogenesis in vitro and in vivo?"
            ]
        },
        {
            "id": "task847-115c271c00a44ce2afd8cfa0bffab415",
            "input": "Pyrethroids are claimed to have a low human toxicity with some neuro- and immunotoxicity. The objective of this study was to investigate the immunotoxicological properties of six commercially used pyrethroids, including natural pyrethrum and synergist piperonyl-butoxide (PBO).', 'PHA-stimulated cultures of T-helper lymphocytes and blood basophil incubates from nonatopic and atopic patients (IgE > 1000 IU) provided cytokine and histamine determination. Western blot analysis was used for the measurement of Th2-specific signal transducer and activator of transcription-6 (STAT6). Pyrethroids and xenobiotics were added 4 h post-plating.', 'We demonstrated that interferon-gamma (IFN-gamma) production and expression was correlated with lymphocyte proliferation, however, interleukin-4 (IL-4) was down-regulated at the end of the 3 day culture. Atopics showed significantly higher IL-4 activity than nonatopics. Pyrethroids inhibited IFN-gamma and IL-4 in both groups at around 10(-5) M. Only fenvalerate and S-bioallethrin combined with 10-fold PBO in the atopic-enriched blood basophil incubates caused a weak but significant increase in histamine release. Histamine acted bidirectionally on STAT6, but pyrethroids inhibited the intracellular Th2-specific STAT6 more effectively in atopics than in nonatopics.",
            "output": [
                "Do pyrethroid insecticides influence the signal transduction in T helper lymphocytes from atopic and nonatopic subjects?"
            ]
        },
        {
            "id": "task847-af4cb24c55d74f52a1fc4cc6f907f6f5",
            "input": "Cellular transcriptional regulatory factor YY1 represses the activity of the early promoter P97 of HPV 16, but the regulatory activity to early promoter P105 of HPV 18 depends on a switch region which locates at the upstream sequences of YY1 binding sites. This study is to find out whether within the HPV 16 LCR there is such motif.', 'DNA sequences of the whole HPV 16 LCR region were analyzed. Two similar switch structures were found. Different CAT reporter plasmids, one containing HPV 16 reference and the other mutated LCRs, both starting at the end of L1 and from the beginning of the enhancer, were generated and transfected in HeLa cells transiently.', 'CAT assays showed there is no change of regulation pattern of YY1 on P97, when the two switch-similar structures were deleted. Sequences analysis also showed that no switch region like motif could be demonstrated in enhancer region, in promoter proximal segment, and even in E6/E7 area.",
            "output": [
                "Is [ No switch region found in the regulatory sequence of HPV 16 for promoter P97 ]?"
            ]
        },
        {
            "id": "task847-01567d054cd14bf5a08e83dcbac30a49",
            "input": "By using the techniques of PCR and restriction fragment length polymorphism (RFLP), we established a classification method for HBV genome based on viral S gene of asymptomatic HBV carriers (AsC).', 'By using this method we classified HBV DNA of AsC living in Guangzhou, Shenyang, Beijing and Chongqing.', 'Among the AsC of Guangzhou, genotype B was 32.8%, genotype C 42.7%, mixed genotypes B and C 23.0%, others 1.6%; among the AsC of Chongqing, genotype B was 35.0%, genotype C 40.0%, mixed genotypes B and C 25.0%; among the AsC of Beijing, genotype B was 25.0%, genotype C 50.0%, mixed genotypes B and C 25.0%; among the AsC of Shenyang, genotype B was 11.1%, genotype C 88.9%. The prevalent HBV strains in China are genotype C and genotype B, and genotype C is the main genotype in west China.",
            "output": [
                "Does [ Establishment of a method for classification of HBV genome and it 's application ]?"
            ]
        },
        {
            "id": "task847-8e93ceab5aec450fba86af4835c3dfd6",
            "input": "Left ventricular (LV) dysfunction is often found in the early stage of human immunodeficiency virus (HIV) infection and deteriorates with disease progression. CD4 lymphocyte count and opportunistic infection are the major indicators for the clinical staging of HIV infection. This study investigated the association of these indicators with LV dysfunction in the clinical course of HIV infection.', 'HIV-positive patients without cardiac manifestations consecutively admitted from May 1998 to April 1999 were enrolled in the study. Echocardiographic LV function evaluation and measurement of CD4 lymphocyte count were performed. Parameters for LV systolic and diastolic functions were compared between patients with CD4 lymphocyte count >or= 200/microL and those with CD4 < 200/microL. In patients with CD4 < 200/microL, LV function was further correlated with the presence or absence of opportunistic infections.', 'Ninety eight HIV-positive patients including 52 with CD4 >or= 200/microL and 46 with CD4 < 200/microL were studied. One half of the 46 patients with CD4 < 200/microL had active opportunistic infections. We found that LV fractional shortening, ejection fraction, and isovolumic relaxation time were all significantly lower in the patients with CD4 < 200/microL compared with those with CD4 >or= 200/microL. Moreover, these LV systolic and diastolic dysfunctions were positively correlated with decreased CD4 lymphocyte count. In contrast, no difference was found in these parameters between patients with and without opportunistic infections. In multiple regression analysis, CD4 lymphocyte count was found to be the only factor for predicting the LV systolic and diastolic dysfunction.",
            "output": [
                "Is left ventricular dysfunction associated with CD4 lymphocyte count rather than opportunistic infection in human immunodeficiency virus infection?"
            ]
        },
        {
            "id": "task847-2f088bbf012a45afa100b327c3d4bc14",
            "input": "The purpose of this study was to evaluate the influence of fresh IVF/ICSI cycle outcome on the prognosis of the related frozen embryo replacement (FER) cycle.', '459 FER cycles, involving 2049 cleavage stage embryos with no or up to 10% fragmentation, were performed for which the outcome of the fresh cycle was recorded. The cycles were divided into two groups; group A included cycles in which cryopreserved embryos were obtained from fresh cycles in which conception occurred. Group B were cycles in which cryopreserved embryos originated from unsuccessful fresh cycles.', 'Groups A and B were comparable with respect to mean (+/- SD) age at cryopreservation (33 +/- 3.9 versus 33.2 +/- 4 years, P = not significant), mean number of oocytes retrieved and fertilized normally in the fresh cycle (11 +/- 5.2 versus 11.2 +/- 4.8, P = not significant) and mean age at the cryo-thawed transfer (34.5 +/- 4.2 versus 33.9 +/- 4 years, P = not significant). No significant difference was found between the two groups with regard to mean number of embryos cryopreserved (6.5 +/- 3.9 versus 6.2 +/- 3.6) and subsequently thawed (4.5 +/- 2.5 versus 4.5 +/- 1.8) per cycle and number of cryo-thawed embryos transferred per cycle (2.0 +/- 0.7 versus 2.1 +/- 0.8). However, the implantation rate per transferred embryo in group A was double that in group B (23 versus 11.2%, P < 0.0001). Moreover, the clinical pregnancy and ongoing pregnancy rates per cycle were significantly higher in group A compared with group B (34.8 and 27.3% versus 15.6 and 13.1%, P < 0.0001 and P = 0.0003 respectively). The difference in FER cycle outcome could not be explained by confounding variables.",
            "output": [
                "Do cryo-thawed embryos obtained from conception cycles have double the implantation and pregnancy potential of those from unsuccessful cycles?"
            ]
        },
        {
            "id": "task847-23760873b1944f30a31aceb40373de13",
            "input": "This study was designed to examine the course of psychological distress and pain from study entry to death in 59 women with metastatic breast cancer participating in a randomized trial of the effects of group psychotherapy on psychosocial outcomes and survival. It was hypothesized that psychological distress would increase significantly before death independent of changes in pain.', 'Data were collected as part of a larger study (N = 125). Analyses were based on data from a subset of women who had died and for whom we had data from at least three assessments. Mean levels of mood, trauma symptoms, depression symptoms, well-being, and pain over three time points were examined: at baseline (T1), the second-to-last assessment before death (T2), and the last assessment before death (T3).', 'Results indicate that while psychological distress remained relatively constant or declined from T1 to T2, means on all measures significantly changed in the hypothesized direction from T2 to T3. Neither self-reported pain, nor the passage of time, appeared to account for these changes. Additionally, participation in group psychotherapy did not have a significant impact on this change in distress proximal to death.",
            "output": [
                "Do psychological distress and pain significantly increase before death in metastatic breast cancer patients?"
            ]
        },
        {
            "id": "task847-720924ef91b64132aed829dddd1ce358",
            "input": "The objective of the present study was to investigate the relationship between colorectal and prostate cancer.', 'All Victorian men who developed metachronous colorectal and prostate cancer with the first primary diagnosed between 1982 and 1993 were identified retrospectively from the Victorian Cancer Registry and were followed up to the end of 1995. Analyses were stratified by age group and years of follow up. The cause of death in those men who had prostate cancer following colorectal cancer was determined. The stage of colorectal cancer was compared between men with and without second primary prostate cancer and the grade of prostate cancer was compared with men who did not have a prior colorectal cancer.', 'Men who develop colorectal cancer are at increased risk of prostate cancer, with the greatest risk in men under the age of 65 (Relative risk approximately 2). Men with first primary colorectal cancer are more likely to develop prostate cancer than colorectal second primaries, and men who develop second primary prostate cancer are more likely to die of prostate cancer than colorectal cancer.",
            "output": [
                "Are men with colorectal cancer predisposed to prostate cancer?"
            ]
        },
        {
            "id": "task847-2766a42880804f8dad8099292c50945e",
            "input": "The relationship between end-stage renal disease (ESRD), hemodialysis, and oxidative stress is controversial. To determine whether ESRD causes oxidative stress, we measured basal levels of plasma F2-isoprostanes as a marker of lipid peroxidation in vivo, and peroxynitrite-stimulated formation of F2-isoprostanes, as a marker of the oxidizibility of plasma lipids in vitro, before and after routine hemodialysis.', 'Total plasma F2-isoprostanes were measured by gas chromatography-mass spectrometry (GC-MS) before and after the oxidation of plasma lipids with the peroxynitrite-generating compound, 3-morpholino-sydnonimine (SIN-1), in 23 patients with ESRD patients undergoing regular hemodialysis, and 14 controls. Plasma vitamin E concentrations were measured by high-performance liquid chromatography (HPLC).', 'There was no difference in basal plasma concentrations of F2-isoprostanes in the ESRD group prior to hemodialysis, 246 +/- 20 pg/mL, compared to controls, 252 +/- 28 pg/mL, or immediately on completion of hemodialysis, 236 +/- 14 pg/mL. Incubation of control plasma with SIN-1 caused the formation of F2-isoprostanes with plasma concentrations increasing to 987 +/- 54 pg/mL at 6 hours. The formation of F2-isoprostanes stimulated by SIN-1 was markedly enhanced in the plasma obtained from patients undergoing hemodialysis at 1861 +/- 174 pg/mL, P < 0.001, and SIN-1-induced formation of F2-isoprostanes was further increased in plasma obtained immediately after hemodialysis at 2437 +/- 168 pg/mL, P < 0.001. Incubation of plasma with SIN-1 resulted in the net consumption of vitamin E.",
            "output": [
                "Is peroxynitrite-induced oxidation of plasma lipids enhanced in stable hemodialysis patients?"
            ]
        },
        {
            "id": "task847-6bcf2c95e1f149ec8326b6e1d4e4b18b",
            "input": "Type II diabetes in the Goto Kakizaki (GK) rats (derived from Wistar rats) is not associated with the development of obesity, hyperlipidemia, hypertension, or pronounced renal functional changes. The aim of this study was to investigate the effect of superimposed hypertension on renal function and morphology under conditions of hyper- and normoglycemia.', 'The evolution of biochemical and morphologic renal changes was examined in GK and Wistar rats treated with deoxycorticosterone acetate (DOCA) salt over 24 weeks.', 'Blood pressure was increased from 6 weeks on in GK and Wistar rats with no difference in blood pressure levels between both groups (week 24, 183 +/- 14 mm Hg vs. 191 +/- 13 mm Hg, P = NS, vs. 144 +/- 6 mm Hg in normal controls, P < 0.01). A progressive increase in proteinuria was observed in hypertensive GK rats from 12 weeks on (week 24, 168 +/- 62 mg/day vs. 41 +/- 30 mg/day in hypertensive Wistar rats, P = 0.002). Histologic analysis at weeks 15 and 24 showed progressive glomerulosclerosis in hypertensive GK and Wistar rats (week 24, 13 +/- 4% vs. 8 +/- 1%, P = NS) but not in nonhypertensive GK controls. This was associated with evidence of podocyte damage (de novo desmin expression) in hypertensive as compared to nonhypertensive GK rats (week 24, score 1.4 +/- 0.1 vs. 0.8 +/- 0.1, P < 0.001) while no significant increase was observed in hypertensive vs. nonhypertensive Wistar rats. Tubulointerstitial damage was increased in hypertensive GK as compared to hypertensive Wistar rats (week 24, score 1.5 +/- 0.6 vs. 0.6 +/- 0.3, P = 0.01). By immunohistochemistry, this was associated with an up-regulation of tubulointerstitial type IV collagen as well as alpha-smooth muscle actin (alpha-SMA) expression, macrophage infiltration and cell proliferation in hypertensive GK rats.",
            "output": [
                "Does hypertension superimposed on type II diabetes in Goto Kakizaki rats induce progressive nephropathy?"
            ]
        },
        {
            "id": "task847-21c834e1a96d4718a3510527ab04664b",
            "input": "Somatic cells in vitro have a finite life expectancy before entering a state of senescence, but it is unclear whether this state occurs in vivo in kidney development, growth, and aging. We previously showed that human kidney cortex displays telomere shortening with age. In this study, we compared the structural and functional changes in rat kidney with age to phenomena associated with cellular senescence in vitro.', 'We assessed the changes in Fischer 344 rat kidneys from age 1 to 9 months to define growth and development and from age 9 to 24 months to define aging.', 'Rat kidney telomeres were approximately 35 to 40 kb long and did not shorten significantly. Expression of mRNA for p16INK4a, a characteristic senescence gene in vitro, was undetectable in most young rats but rose 27 fold during growth and a further 72-fold during aging. p16INK4a protein was localized to the nucleus and increased with age. p16INK4a mRNA also increased in other tissues. Lipofuscin and senescence-associated beta-galactosidase increased in epithelium with growth and aging and their occurrence was significantly associated with each other. Lipofuscin was particularly found in atrophic nephrons.",
            "output": [
                "Does cell senescence in rat kidneys in vivo increase with growth and age despite lack of telomere shortening?"
            ]
        },
        {
            "id": "task847-1614a72f73a4429591bcbe53ba07be4d",
            "input": "Very low birth weight (VLBW) infants are at risk to develop nephrocalcinosis (NC). NC may result from spontaneous or therapy-induced imbalance between promoters and inhibitors of crystallization in the urine. However, data on \"normal\" urinary excretions of these parameters in VLBW infants are sparse. Therefore, we prospectively examined the urinary excretion of calcium, oxalate, uric acid, and citrate in VLBW infants during the first 8 weeks of life.', 'Urine samples were collected once weekly in 124 VLBW infants. NC appeared in 16 infants, whose data were separately analyzed. The remaining 108 infants were divided into subgroups: A, <1000 g (N = 53); and B, 1000 to 1500 g (N = 55). Random urine samples were analyzed and the results were expressed as molar creatinine ratios. Calcium/citrate and oxalate/citrate expressed the risk for calcium oxalate crystallization.', 'In group A, citrate excretion was lower at weeks 2 to 5 and 7; calcium/citrate was higher in weeks 2, 4, and 7; oxalate/citrate was higher in weeks 3, 4, 7, and 8; and calcium/creatinine ratio was higher in week 4 (P < 0.05). Citrate/creatinine ratios were low in nine infants with NC. Oxalate/creatinine and calcium/creatinine were elevated in five and calcium/citrate was increased in nine infants with NC.",
            "output": [
                "Is hypocitraturia one of the major risk factors for nephrocalcinosis in very low birth weight ( VLBW ) infants?"
            ]
        },
        {
            "id": "task847-7fec9e0ffb6e492ea0fa49897f6fe807",
            "input": "Recent studies have suggested that apoprotein (apo) CI in very low-density lipoprotein (VLDL) plays an important role in causing hypertriglyceridemia independent of apo CIII, which is associated with coronary heart disease (CHD). Because the incidence of CHD is increased in diabetic patients and is even higher when diabetic nephropathy is developed, we measured apo CI levels in VLDL from type 2 diabetic patients, with various degree of nephropathy, and compared the results with those for healthy controls or nondiabetic patients with chronic renal failure (CRF).', 'This study enrolled healthy control subjects, type 2 diabetic patients with normoalbuminuria, microalbuminuria, overt proteinuria, and CRF on hemodialysis and nondiabetic hemodialysis patients. VLDL (density <1.006) was separated by ultracentrifugation. Then the apo CI, CIII, and B concentrations in VLDL were measured by enzyme-linked immunosorbent assay (ELISA).', 'The apo CI, CIII, and B concentrations in VLDL were respectively 3-, 2-, and 2-fold higher, respectively, in diabetic patients with overt proteinuria than in controls. Hemodialysis patients with diabetic nephropathy had levels of apo CI, CIII, and B in VLDL that were 2.6-, 2.7- and 2-fold higher, respectively, than those in controls. Nondiabetic hemodialysis patients also had a 2.7-fold higher level of VLDL apo CIII, whereas VLDL apo CI and VLDL apo B were not significantly increased. VLDL apo CI was significantly correlated with VLDL apo B independently of VLDL apo CIII level.",
            "output": [
                "Is very low-density lipoprotein-apoprotein CI increased in diabetic nephropathy : comparison with apoprotein CIII?"
            ]
        },
        {
            "id": "task847-a7f353b0d62f4c0e8386db0c1d2d314b",
            "input": "Contralateral groin exploration in children with unilateral inguinal hernia is still controversial, particularly in infants. The patency rate of processus vaginalis is highest in infants but there are few data on the subsequent risk of contralateral hernia development in infants. In this retrospective study, we aimed to find out the incidence of contralateral inguinal hernia following unilateral inguinal herniotomy in infants aged less than one year.', 'All infants who underwent a unilateral Inguinal herniotomy between January 1990 and December 1998 were studied retrospectively. Infants with bilateral hernia (n = 7) were excluded from the study.', 'One hundred and one infants (93 boys and 8 girls) were studied. Median age at operation was 23 (range 2-52) weeks. The herniotomy was right-sided in 75% of the infants. Follow-up ranged from three and a half years to 11 years. A contralateral hernia developed in nine infants (9.0%). One of the initial hernias was incarcerated. Median time from operation to occurrence of contralateral hernia was 18 (range 2-60) months. None of the contralateral hernia was incarcerated. Age, sex, incarceration and side of initial hernia did not influence the development of contralateral hernia.",
            "output": [
                "Is contralateral groin exploration justified in infants with a unilateral inguinal hernia?"
            ]
        },
        {
            "id": "task847-f2c7cc30f58e41c3b4934236cc4a2bd0",
            "input": "To define whether immunosuppressive agents that block the interleukin (IL)-2 pathway could prevent activation-induced cell death of activated T cells in the graft, we measured expression of IL-2, IL-2 receptor alpha chain (CD25), IL-15, Fas, and Fas ligand by real time reverse transcription-polymerase chain reaction in cardiac allografts.', 'We characterized the phenotype of the infiltrating cells (CD3, CD68, CD25) by immunohistochemistry. The proportion of apoptotic graft-infiltrating cells was determined by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. We analyzed endomyocardial biopsy specimens from cardiac allograft recipients who were treated with anti-CD25 monoclonal antibody (mAb) induction therapy (daclizumab) or with matching placebo in combination with cyclosporine, steroids, and mycophenolate mofetil.', 'Treatment with anti-CD25 mAb affected the number of infiltrating CD3 and CD68 cells and the IL-2-regulated apoptotic pathway. During anti-CD25 mAb treatment, significantly lower intragraft IL-2 and CD25 mRNA transcription levels and decreased numbers of CD25+ T cells were found compared with the levels measured in endomyocardial biopsy specimens from placebo-treated patients (5- to 10-fold, P=0.002 and P<0.0001, respectively). In these samples the intragraft mRNA expression levels of IL-15 were also lower (P=0.02). Inhibition of the IL-2 pathway by anti-CD25 mAb therapy was accompanied by reduced mRNA and protein of Fas ligand and not by reduced Fas expression (P=0.001 and P=0.03). TUNEL staining revealed that the proportion of graft-infiltrating cells was lower in the anti-CD25 mAb patient group than the proportion of apoptotic cells in patients receiving placebo (P=0.06).",
            "output": [
                "Does anti-CD25 monoclonal antibody therapy affect the death signals of graft-infiltrating cells after clinical heart transplantation?"
            ]
        },
        {
            "id": "task847-095bc93fe1be49db9011dad39e5853a7",
            "input": "The effects of plasterboard composition on Streptomyces californicus growth and bioactivity of spores were studied.', 'Streptomyces californicus was grown on 13 modified plasterboards under saturated humidity conditions. The total content of fatty acid methyl esters was used for quantifying S. californicus biomass, while the spore-induced cytotoxicity and production of nitric oxide (NO), tumour necrosis factor-alpha, and interleukine-6 (IL-6) in mouse macrophages was used to assess the bioactivity of spores. Removal of starch completely from the plasterboard or only from the core reduced significantly the biomass production and the biological activity of spores in comparison with reference board. The biocide added into the core or on the liner decreased the growth markedly and inhibited the sporulation totally. The biomass production correlated positively with the spore number, cytotoxicity, and production of NO and IL-6.",
            "output": [
                "Does starch in plasterboard sustain Streptomyces californicus growth and bioactivity of spores?"
            ]
        },
        {
            "id": "task847-4839e6062e3543298491bb57731aca46",
            "input": "To examine the direct effect of high glucose levels on primary cultured human retinal capillary endothelial cells (HRCEC).', 'HRCECs were isolated from donated eyes and cultured for 6 days in the media containing 5 or 25 mmol/L glucose. The cell viability was determined by trypan blue exclusion assay and cell cycle analyzed by flow cytometry, with the cell apoptosis assayed by TUNEL method.', 'The cell viability was significantly decreased after exposure to 25 mmol/L glucose, and the number of apoptotic cells determined by flow cytometry and TUNEL was significantly increased in response to high-dose glucose treatment.",
            "output": [
                "Does [ High-dose glucose induce human retinal endothelial cell apoptosis ]?"
            ]
        },
        {
            "id": "task847-726b11d2aa6b47f396fa59612201e155",
            "input": "To identify factors that influence peri-operative hemorrhage in view of reducing the need for transfusions in patients undergoing trans uretheral resection of prostate (TURP).', 'All patients undergoing TURP between January 1997 and December 1999 were identified using ICD 9CM coding and indexing system. Overall 430 patients were identified, however, 384 charts were included and reviewed for demographics, pre and intra-operative data and post-operative morbidity. Patients were divided into two groups on the basis of presence of significant hemorrhage.', 'Overall 384 patients were analyzed. Nineteen patients had hemorrhage--group I whereas 365 had no significant hemorrhage--group II. Mean age and co-morbidities in the two groups were similar. However, in group I, 58% presented with urinary retention compared to 33% in group II. In group I, factors that reached statistical significance include; operative time (p<0.05), mean resected tissue weight (p<0.02), and patient presentation (urinary retention) (p<0.032). There was no significant difference in the two groups with respect to type of anesthesia (regional versus general) and histology of the resected tissue. Patients with mean pre-operative hemoglobin of 10.6 % had a 37% transfusion rate.",
            "output": [
                "Does optimization of low pre-operative hemoglobin reduce transfusion requirement in patients undergoing transurethral resection of prostate?"
            ]
        },
        {
            "id": "task847-0f57ae113cd14016b902e1f5974cfc5b",
            "input": "To examine the effect of heparin-coated balloon-expandable iliac stent placement on intimal hyperplasia in a baboon model.', 'Balloon-expandable (Palmaz-Schatz) stents were placed in bilateral common iliac arteries in 20 male baboons (mean weight: 8.8 kg). In each animal, a heparin-coated iliac stent was placed on one side and the contralateral iliac artery received an uncoated stent that served as a control. The iliac artery stents were harvested at 30 days (n = 10) and 90 days (n = 10). Arteriography was performed to assess iliac patency and intravascular ultrasonography was used to determine neointimal and luminal areas. Histologic and morphometric analysis and scanning electron microscopy were performed in the stent-implanted iliac arteries.', 'One animal was excluded in the 30-day group because of premature death. In the remaining nine surviving animals, seven control stents (78%) and nine heparin-coated stents (100%) remained patent. Morphometric analysis showed that the iliac arteries with heparin-coated stents had larger luminal areas (17%, P <.05), less neointimal area (26%, P <.05), lower neointima-to-media ratios (32%, P <.05), and equivalent medial areas (P =.92) compared to the control group at 30 days. In contrast, all control and heparin-coated stents were patent (100%) in the 90-day group. In that group, the heparin-coated stent group had less neointimal area (28%, P <.05), lower neointima-to-media ratios (42%, P <.05), and equivalent medial area (P =.92) and luminal area (P =.07) compared to the control group.",
            "output": [
                "Does heparin-coated balloon-expandable stent reduce intimal hyperplasia in the iliac artery in baboons?"
            ]
        },
        {
            "id": "task847-e4b8a29b9cd1491589b041224a40cb51",
            "input": "Differences in mortality are thought to exist between African Americans and Caucasians with heart failure. These differences may be due to a variety of factors, including differences in disease process, socioeconomic status, and access to health care. Additionally, little data exist on racial differences between these two groups after cardiac transplantation. This study examines a single center, urban experience in treating African Americans and Caucasians with heart failure and after cardiac transplantation. We hypothesize that treatment in a specialized, comprehensive heart failure/cardiac transplantation program results in similar survival between African Americans and Caucasians.', 'We retrospectively reviewed the Rush Heart Failure and Cardiac Transplant Database from July 1994 to August 2000. Variables analyzed in the cardiomyopathy patients included survival (until death, placement of left ventricular assist device or cardiac transplantation), number of hospitalizations per year, length of stay per year, and utilization of outpatient resources. Follow-up period was from initial visit to death, transplantation, or implantation of left ventricular assist device. In those who underwent cardiac transplantation, we examined rejection rates (cellular and humoral), rejection burden, hospitalization data, and 5-year survival. A subgroup bridged to cardiac transplantation with a left ventricular device was also analyzed.', 'Seven hundred thirty-four cardiomyopathy patients were identified: 203 were African Americans and 531 were Caucasians. The etiology of cardiomyopathy was more commonly ischemic in Caucasians as compared to non-ischemic in African Americans (P <.01). African Americans had more admissions to the hospital per year compared with Caucasians, 1.2 +/- 2.1 versus.5 +/- 1.1 (P <.01) with longer length of stay per year, 1.4 +/- 25.2 days versus 4.4 +/- 14.3 days (P <.01). Utilization of outpatient resources was significantly higher in African Americans compared with Caucasians with more use of continuous inotropes (13% versus 6%, P <.01), intermittent inotropes (11% versus 5%, P <.01), and home nursing after hospital discharge (52% versus 32% of hospital discharges, P <.01). Survival by Kaplan-Meier analysis was comparable between the two groups (mean survival 1,470 +/- 72 days in African Americans versus 1521 +/- 46 days in Caucasians, log rank test [P =.6]). During this time, 30 African Americans and 73 Caucasians underwent cardiac transplantation. Fifty-three were bridged to transplantation with a left ventricular assist device (20 African Americans, 33 Caucasians). There were no differences in 5-year survival by Kaplan-Meier analysis despite higher peak preoperative panel reactive antibody levels in African Americans versus Caucasians (12% +/- 30% compared with 5% +/- 15%, P =.04), more overall treated rejection episodes per year in the African Americans (P <.01), as well as more posttransplant hospitalizations (2.2 +/- 1.2 times per year as compared with 1.7 +/- 2.1 times per year, P =.04).",
            "output": [
                "Are influence of race in heart failure and cardiac transplantation : mortality differences eliminated by specialized , comprehensive care?"
            ]
        },
        {
            "id": "task847-d473d101824c48bea5b7050c298c60bc",
            "input": "We previously demonstrated in rats that intravenous infusion of a lipid emulsion increases survival in resuscitation from severe bupivacaine cardiac toxicity. The present studies were undertaken to determine if this method is similarly effective in a non-rodent model using a larger animal.', 'Bupivacaine, 10 mg/kg, was administered intravenously over 10 seconds to fasted dogs under isoflurane general anesthesia. Resuscitation included 10 minutes of internal cardiac massage followed with either saline or 20% lipid infusion, administered as a 4-mL/kg bolus followed by continuous infusion at 0.5 mL/kg/min for 10 minutes. Electrocardiogram (EKG), arterial blood pressure (BP), and myocardial pH (pHm) and pO2 (pmO2) were continuously measured.', 'Survival after 10 minutes of unsuccessful cardiac massage was successful for all lipid-treated dogs (n = 6), but with no survivors in the saline controls (n = 6) (P <.01). Hemodynamics, PmO2, and pHm were improved during resuscitation with lipid compared with saline treatment in which dogs did not recover.",
            "output": [
                "Does lipid emulsion infusion rescue dogs from bupivacaine-induced cardiac toxicity?"
            ]
        },
        {
            "id": "task847-a16861f46f274c69ba97b91885e48666",
            "input": "The regulation of the immediate-early gene c-fos serves as a paradigm for signal-activated gene induction. Lysophosphatidic acid is a potent serum-borne mitogen able to induce c-fos.', 'Analysing the signalling events following stimulation of mouse embryonic stem cells with serum and lysophosphatidic acid, we show that the extracellular signal-regulated kinase (ERK) pathway is involved in mediating c-fos induction. We demonstrate that the ERK-activated kinase MSK1 is required for full c-fos promoter activation, as well as for the phosphorylation of cAMP-responsive element (CRE) binding proteins. We propose that MSK1 contributes to ERK-mediated c-fos promoter activation by targeting CRE binding proteins.",
            "output": [
                "Is the kinase MSK1 required for induction of c-fos by lysophosphatidic acid in mouse embryonic stem cells?"
            ]
        },
        {
            "id": "task847-a24bd3d26d5f40a2a5999e42c06fbf4b",
            "input": "The theoretical effects on corneal transparency induced by changes in collagen fibril packing following phototherapeutic keratectomy were compared to changes in objective measurements of haze.', 'Phototherapeutic keratectomy was performed on the right eyes of four young rabbits; left eyes were used as controls. Postoperative slit-lamp measurements of haze were taken at regular intervals up to 19 months. Wounded stromas were studied by synchrotron x-ray diffraction to calculate the average interfibrillar spacing of the collagen fibrils. These data were combined with transmission electron microscope measurements, and the summation of scattered fields method was used to predict the transmission of visible light.', 'Objective measurements of haze were higher than the baseline control throughout the study. Electron micrographs of anterior stroma in 8-month-old wounds displayed irregularly spaced and poorly organized fibrils and x-ray diffraction indicated larger mean interfibrillar spacing compared to the controls. However, the predicted transmission of visible light through the anterior stromal scar tissue was not significantly different than normal.",
            "output": [
                "Do persistent haze and disorganization of anterior stromal collagen appear unrelated following phototherapeutic keratectomy?"
            ]
        },
        {
            "id": "task847-37d9614332004c43b1ed958b38b8931e",
            "input": "Diabetes, arterial hypertension, hypercholesterolemia, and aging are associated with endothelial dysfunction in various vasculatures. Endothelium-dependent vasodilation of the renal vasculature cannot be easily assessed, but infusion of L-arginine, the substrate of endothelial nitric oxide synthase, leads to an increase in renal plasma flow (RPF) in humans. We have examined the effect of L-arginine infusion on renal hemodynamics in hypertensive patients with type 2 diabetes.', 'Twenty-three elderly patients with type 2 diabetes (age, 65 +/- 6 years; HbA(1c), 7.8 +/- 1.6%) with coexisting arterial hypertension (158 +/- 19/83 +/- 11 mmHg) and elevated cholesterol levels (total cholesterol, 215 +/- 33 mg/dl) were examined. These patients were compared with a young and healthy reference group (n = 20; age, 26 +/- 2 years). The effect of L-arginine infusion (100 mg/kg over 30 min) on RPF and glomerular filtration rate were measured using the constant input clearance technique with p-aminohippurate and inulin, respectively.', 'L-arginine infusion similarly influenced renal hemodynamics in patients and reference subjects: RPF increased by 7 +/- 11 and 7 +/- 11% in diabetic and reference subjects, respectively (P = NS). Other parameters of renal hemodynamics such as glomerular filtration rate (5 +/- 5 vs. 4 +/- 4%) and filtration fraction (-1 +/- 8 vs. -1 +/- 9%) were not significantly different between diabetic and reference subjects, too.",
            "output": [
                "Is l-arginine-induced vasodilation of the renal vasculature altered in hypertensive patients with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-ba7398d463624f5383954553765e4510",
            "input": "Current knowledge of the potential effects that several dietary lipids exert on immune functions indicates that these substances participate actively in the modulation of immune system by which they contribute to the improvement of the conditions of patients suffering from inflammatory disorders. However, long-chain n-3 polyunsaturated fatty acids induce an immunosuppressive status that leads to a reduction of the host natural resistance to infectious agents as well as to an enhancement of oxidative damage. Hence, the present study has been designed to evaluate the effects on the immune system of the antioxidant N-acetyl-L-cysteine (NAC) in mice fed dietary lipids and infected with Listeria monocytogenes.', 'Balb/c mice were fed for 4 weeks with diets containing either olive oil (OO, 20% by weight), fish oil (FO, 20% by weight) or hydrogenated coconut oil (HCO, 20% by weight). After dietary lipid administration mice were experimentally infected with L. monocytogenes or treated with NAC (25mg/ml intraperitoneally).', 'NAC at a concentration of 1mM promoted a loss of cell viability, although no differences were observed among the four groups. After injection of NAC in combination with L. monocytogenes, 25% of mice fed a low-fat (LF) diet survived. However, in the groups fed dietary lipids no effect on survival of mice was found. NAC participated in the reduction of superoxide anion generation measured with nitroblue tetrazolium (NBT) in the group fed a FO diet. Finally, NAC reduced the recovery of L. monocytogenes from spleen of mice fed diets containing LF or HCO.",
            "output": [
                "Do anti-oxidant properties of N-acetyl-L-cysteine improve the immune resistance of mice fed dietary lipids to Listeria monocytogenes infection?"
            ]
        },
        {
            "id": "task847-aa8d404b2e284d79847ab25741384e76",
            "input": "Smooth muscle cells (SMC) of the bladder undergo hypertrophy and hyperplasia following exposure to sustained mechanical overload. Although superficial similarities in the response of the heart and bladder to hypertrophic stimuli suggest that similar molecular mechanisms may be involved, this remains to be demonstrated. In this study we compared signal transduction pathway activation in primary culture bladder SMC and cardiac myofibroblasts in response to cyclic stretch. The effects of growth factor stimulation on pathway activation in bladder SMC were also investigated.', 'Primary culture rodent bladder SMC or cardiac myofibroblasts were subjected to cyclic stretch-relaxation in the absence or presence of pharmacologic inhibitors of the phosphoinositide-3-kinase, (PI3K)/Akt, extracellular signal-regulated kinase-mitogen activated protein kinase (Erk-MAPK) or the p38 stress-activated protein kinase-2 (SAPK2) pathways. In parallel experiments human bladder SMC were treated with platelet-derived growth factor-BB (PDGF-BB), heparin-binding EGF-like growth factor (HB-EGF) or fibroblast growth factor-2 (FGF-2). In each case the extent of DNA synthesis was determined by uptake of tritiated thymidine, and activation of specific signaling intermediates was determined by immunoblot analysis using antibodies to the non-phosphorylated and phosphorylated (activated) forms of Akt, p38 and Erk1/2.', 'Akt and p38 were rapidly phosphorylated in stretched bladder SMC and cardiac myofibroblasts, and stretch-induced DNA synthesis in these cells was ablated with inhibitors of PI3K or p38 but not Erk-MAPK. Similarly, PDGF-BB up-regulated DNA synthesis in bladder SMC in a p38 and Akt-dependent manner.",
            "output": [
                "Does signaling through PI3K/Akt mediate stretch and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells?"
            ]
        },
        {
            "id": "task847-363668f539434df5a06e01155fd9a81b",
            "input": "To assess the activity and tolerability of temozolomide in children with progressive low-grade gliomas (LGGs).', \"The authors reviewed the records of 13 children (6 months to 19 years old) with progressive LGGs and magnetic resonance imaging evidence of unresectable tumors who were treated with temozolomide at the authors' institution since 1999.\", 'Four patients received a 5-day regimen of temozolomide (150 mg/m2 per day) repeated every 28 days, and nine patients received a 42-day regimen (75 mg/m2 per day) repeated every 56 days. Three patients demonstrated partial responses to temozolomide, with a median time to maximal response of 5 months (range 4-12 months), and one had a minor response at 9 months. Four patients developed progression while on temozolomide, with a median time to progression of 7 months (range 1-12 months). Five patients had disease stabilization. Among the five patients with prior chemotherapy and/or radiation therapy, temozolomide was associated with disease stabilization in three and tumor response in one. In the three patients with neurofibromatosis type 1, two patients experienced tumor responses and one disease stabilization. Thrombocytopenia, nausea, emesis, and fatigue were the most common toxicities. Four patients discontinued therapy because of the side effects.",
            "output": [
                "Is temozolomide active in childhood , progressive , unresectable , low-grade gliomas?"
            ]
        },
        {
            "id": "task847-f3b2a7efe3a748ef9825c84855e50e72",
            "input": "SCF (Skp1-Cullin-F-box) complexes are a major class of E3 ligases that are required to selectively target substrates for ubiquitin-dependent degradation by the 26S proteasome. Conjugation of the ubiquitin-like protein Nedd8 to the cullin subunit (neddylation) positively regulates activity of SCF complexes, most likely by increasing their affinity for the E2 conjugated to ubiquitin. The Nedd8 conjugation pathway is required in C. elegans embryos for the ubiquitin-mediated degradation of the microtubule-severing protein MEI-1/Katanin at the meiosis-to-mitosis transition. Genetic experiments suggest that this pathway controls the activity of a CUL-3-based E3 ligase. Counteracting the Nedd8 pathway, the COP9/signalosome has been shown to promote deneddylation of the cullin subunit. However, little is known about the role of neddylation and deneddylation for E3 ligase activity in vivo.', 'Here, we identified and characterized the COP9/signalosome in C. elegans and showed that it promotes deneddylation of CUL-3, a critical target of the Nedd8 conjugation pathway. As in other species, the C. elegans signalosome is a macromolecular complex containing at least six subunits that localizes in the nucleus and the cytoplasm. Reducing COP9/signalosome function by RNAi results in a failure to degrade MEI-1, leading to severe defects in microtubule-dependent processes during the first mitotic division. Intriguingly, reducing COP9/signalosome function suppresses a partial defect in the neddylation pathway; this suppression suggests that deneddylation and neddylation antagonize each other.",
            "output": [
                "Is neddylation and deneddylation of CUL-3 required to target MEI-1/Katanin for degradation at the meiosis-to-mitosis transition in C. elegans?"
            ]
        },
        {
            "id": "task847-61b3cc76e830403fb1389b6fb4673747",
            "input": "Both the epidermal growth factor receptor (EGFR) and the p53 homologue p63 are overexpressed in a significant number of cases of head and neck squamous cell carcinoma (HNSCC). Epidermal growth factor receptor and p63 both possess oncogenic properties, including the potential to increase cell proliferation and antagonize apoptosis. ZD1839 (\"Iressa\") is an adenosine triphosphate-competitive inhibitor specific to the EGFR tyrosine kinase currently under evaluation as a chemotherapeutic agent in HNSCC. The objective was to investigate whether p63 expression is decreased after treatment of HNSCC cells with ZD1839. Downregulation of p63 by ZD1839 would identify a potential molecular relationship between EGFR signaling and p63 and could provide insight into the mechanism of action of ZD1839.', 'In vitro examination of p63 expression after ZD1839 treatment.', 'A human HNSCC cell line, SCC-012, was treated with varying doses of ZD1839. p63 protein and messenger RNA levels were analyzed by Western and Northern blot analyses. The effect of ZD1839 on SCC-012 cell cycle was analyzed by flow cytometric analysis.', 'In SCC-012 cells there was a dose-dependent decrease in p63 protein and messenger RNA levels over the course of ZD1839 treatment. Levels of phosphorylated MAPK decreased and p27KIP-1 levels increased after ZD1839 treatment. ZD1839 treatment induced a twofold increase in G1-phase cells and a 3.5-fold decrease in S-phase cells consistent with growth arrest.",
            "output": [
                "Does inhibition of epidermal growth factor receptor signaling decrease p63 expression in head and neck squamous carcinoma cells?"
            ]
        },
        {
            "id": "task847-6df973b1eff24ad28fdb91be4ab9d0cc",
            "input": "Acute myeloid leukemia (AML) cells express the cell surface antigen CD33 that can function as a downregulator of cell growth, mediating growth arrest and apoptosis. The protein kinase Syk is an essential element in several cascades coupling certain antigen receptors to cell responses. Recently we reported that CD33 recruits Syk for its signaling in AML cell lines. In this study, we further investigated the mechanism(s) of Syk engagement in CD33 signaling in primary AML samples.', 'We investigated 25 primary AML samples for their proliferative response (3H-thymidine incorporation) and biochemical changes (Western blot analysis) to anti-CD33 mAb treatment.', 'Proliferation studies demonstrated that 14 (56%) of AML samples were responsive (R) while 11 (44%) were nonresponsive (n-R) to inhibitory antibody activity. Seven of 25 AML samples (28%) expressed undetectable levels of Syk. However, cells from two of these patients expressed the ZAP-70 protein kinase. In Syk/ZAP-70(+) samples, CD33 ligation inhibited proliferation in 70% of cases, while none of the Syk/ZAP-70(-) samples was responsive. There were significant biochemical differences between responder and nonresponder AML populations. In responder samples, CD33 ligation induced phosphorylation of CD33 andSyk and formation of the CD33/Syk complex. In nonresponder samples, CD33 was not phosphorylated, and Syk was in complex with the SHP-1 protein phosphatase constitutively.",
            "output": [
                "Does the inhibitory effect of anti-CD33 monoclonal antibodies on AML cell growth correlate with Syk and/or ZAP-70 expression?"
            ]
        },
        {
            "id": "task847-7b0ba2e0919449a186c3ca7766b3d6c4",
            "input": "Increased levels of allergen-reactive immunoglobulins (Igs) have been reported in nasal fluids from patients with intermittent allergic rhinitis (IAR) sensitive to ragweed and grass. The aims of this study were to make a detailed characterization of nasal fluid Igs in birch pollen-induced IAR.', 'Nasal fluids were obtained from 23 patients with birch pollen-induced IAR during and after the birch pollen season, and from 20 healthy controls. Nasal fluid total and Bet v 1-reactive (IgA), IgE and IgG as well as albumin were analyzed by immunoassays. The integrity of IgA and IgG, and the molecular form of IgA were assessed by Western blotting and column fractionation, respectively.', 'Nasal fluid total IgE and IgG, but not IgA, were higher in patients compared with controls. Western blotting indicated no significant degradation of IgA (including S-IgA) and IgG. Most of the IgA, including Bet v 1-reactive antibodies, was of the secretory form and of the IgA1 subclass. Bet v 1-reactive IgA and IgG were present in all patients, but was mostly nondetectable in controls. No significant differences in the levels of Bet v 1-reactive IgA and IgG were found in patients during the birch pollen season compared with off season. Both Bet v 1 and Bet v 2-reactive IgE were nondetectable in most samples.",
            "output": [
                "Are allergen-reactive antibodies found in nasal fluids from patients with birch pollen-induced intermittent allergic rhinitis , but not in healthy controls?"
            ]
        },
        {
            "id": "task847-79b583015e604bc3bc796728423ad53c",
            "input": "Nasal polyposis (NP) is a chronic inflammatory disease often found coexisting with asthma. As this disorder tends to cluster in families, a genetic predisposition has been suggested. Interleukin-1 (IL-1) has been proposed to play a role in the pathogenesis of NP.', 'We analysed the single G-to-T base exchange polymorphism in exon 5 at +4845 of the gene encoding IL-1alpha (IL1A) and the C-to-T base exchange polymorphism at -511 of the gene encoding IL-1beta (IL1B) in a population-based sample of adult asthma patients (n = 245). The data were assessed for correlation with data on history of NP and other phenotype-related characteristics.', 'The prevalence of NP in our study group was 14.3%. The distribution of the IL1A genotype differed significantly between asthmatics with and without NP (P = 0.005). The risk of NP was markedly increased in allele G homozygous subjects (OR = 2.73; 95%CI = 1.40-5.32). In the case of IL1B we found no significant associations. Asthmatics with NP had more symptoms than others, but lung function and blood eosinophil counts were similar.",
            "output": [
                "Is the IL1A genotype associated with nasal polyposis in asthmatic adults?"
            ]
        },
        {
            "id": "task847-72c5bd95da224156a4b537a4e1ca3d25",
            "input": "The hypothesis that paraoxonase (PON1) has a role in preventing atherosclerosis is based on experimental, transgenic, and case-control studies but has not previously been tested prospectively.', 'The Caerphilly Prospective Study is a cohort study of men aged 49 to 65 years observed for coronary heart disease (CHD) events (fatal and nonfatal myocardial infarction) over a mean period of 15 years. Serum PON1 activity toward paraoxon was measured in 1353 participants. PON1 activity was 20% lower in the 163 men who had a coronary event (P=0.039). Men in the highest quintile of PON1 activity had a decreased risk compared with those in the lowest quintile (OR 0.57 [95% CI, 0.33 to 0.96]). The inverse relationship between quintiles of serum PON1 activity and CHD risk was graded, the median change in OR across each quintile being 0.87 (0.77 to 0.98). After adjustment for all other CHD risk factors, including HDL cholesterol, this median value became 0.90 (0.78 to 1.02). PON1 was most predictive of a new CHD event in patients at highest risk by virtue of preexisting CHD (adjusted median OR for each quintile, 0.74 [0.59 to 0.93]; n=313) or the presence of other risk factors. For the highest tertile of CHD risk (n=390) calculated by the Framingham equation, adjusted median OR for each quintile was 0.84 (0.66 to 1.05); n=390.",
            "output": [
                "Does low paraoxonase activity predict coronary events in the Caerphilly Prospective Study?"
            ]
        },
        {
            "id": "task847-961a388c13b349869e3b4ff6da741069",
            "input": "Postural tachycardia syndrome (POTS) is related to defective peripheral vasoconstriction of dependent extremities with redistributive hypovolemia.', 'To test whether enhanced microvascular filtration produces leg enlargement, we studied 12 patients 13 to 19 years of age with POTS and defective leg vasoconstriction and 13 age-matched healthy control subjects, with strain-gauge plethysmography used to measure venous pressure (Pv), forearm and calf blood flow, vascular capacitance, and the microvascular filtration coefficient (Kf). Measurements were made while the patient was supine and at steady state during upright tilt to 35 degrees. Supine Pv was not different in POTS, but upright leg Pv tended to be increased above control. Arm and leg peripheral arterial resistance was decreased in the supine and upright positions in patients with POTS compared with control subjects (P=0.01, upright legs). Supine Kf was not significantly increased in the forearm in patients with POTS but was increased in the calf (9.3+/-2.2 versus 5.7+/-2.4 [10(-3)] mL/100 mL per minute per mm Hg, P=0.04), correlating with calf blood flow (rs=0.84, P=0.002). Kf was invariant with orthostasis. The hydraulic contribution to upright filtered flow at 35 degrees tilt, the product of Kf and Pv, was approximately twice that of control (0.41+/-0.09 versus 0.19+/-0.04 mL/100 mL per minute, P=0.04).",
            "output": [
                "Is microvascular filtration increased in postural tachycardia syndrome?"
            ]
        },
        {
            "id": "task847-c5ce186d343540d39bb67ae5882419ed",
            "input": "Recurrence after surgery for secondary hyperparathyroidism is not infrequent. Regrowth of the residual parathyroid tissue after subtotal parathyroidectomy or of the autograft after total parathyroidectomy occurs in many cases. Supernumerary glands are also frequently cited as the offending cause and upon revisiting the neck, the surgeon may be surprised that such an obvious gland was 'missed' at the first operation. Indeed, multiple glands removed in sequential operations have been reported suggesting that they develop over time rather than being present from the start. It is possible that microscopic parathyroid 'rests' of embryological origin proliferate under the ongoing stimulus of renal failure to produce supernumerary glands after apparently adequate initial surgery for hyperparathyroidism. The aim of the present study was to determine whether such rests occur frequently or infrequently.\", 'Operative details and pathology results from 60 consecutive parathyroidectomies were reviewed and the occurrence of parathyroid rests noted.', 'Parathyroid rests were found in 37% of extra parathyroidal tissues submitted for analysis. These rests were found commonly in the thymus. The potential significance of such parathyroid rests undergoing hyperplasia in response to the ongoing stimulus of renal failure and leading to recurrent hyperparathyroidism is discussed.",
            "output": [
                "Does embryonic parathyroid rest occur commonly and have implications in the management of secondary hyperparathyroidism?"
            ]
        },
        {
            "id": "task847-ba64a7774b254439914ec8e45bc7de70",
            "input": "In a number of experimental models of nephropathy, heparin is renoprotective because it inhibits mesangial matrix synthesis and cell proliferation; in most of these models, glomerular macrophage infiltration has a pathogenic role. We investigated the hypothesis that heparin might also be renoprotective by modulating the macrophages in various ways in the chronic puromycin glomerulosclerosis model.', 'We studied the effect of a 3 month course, two different dosages of a non-anticoagulant heparin by immunohistochemical evaluation of the number of macrophages (ED-1 positive cells) in glomeruli, as well as the expression and deposition of TGF-beta and latent TGF-beta binding protein in foam cells and mesangial matrix.', 'The renoprotective effect of heparin in this model was confirmed by our observation of lower urine protein and albumin excretion, and a reduced glomerular sclerosis score. These effects were associated with the prevention of macrophage glomerular infiltration, and the inhibition of the TGF-beta axes in foam cells as shown by the reduction in cytoplasm immunostaining for TGF-beta and LTBP-1; heparin also reduced peri-macrophagic collagen IV deposition.",
            "output": [
                "Does heparin reduce glomerular infiltration and TGF-beta protein expression by macrophages in puromycin glomerulosclerosis?"
            ]
        },
        {
            "id": "task847-9851d96b82764a898b401e659e73f146",
            "input": "The effectiveness of partial resuscitation after hypovolemic hemorrhagic shock with deferment of full resuscitation is critical to successful hypotensive resuscitation.', 'To quantitatively address this issue, 40 canines were bled under anesthesia to a mean oxygen debt (O(2)D) of 104 +/- 7.6 mL/kg over 60 minutes (mortality, 40%). Animals surviving the shock were then immediately resuscitated with 0%, 8.4%, 15%, 30%, or 120% (full resuscitation) of shed volume as 5% albumin and held for 2 hours postshock, when the remaining portion of full resuscitation volume was given. Animals were followed for 7 days postshock with hepatic and renal function studies, and then, under anesthesia, cardiac output and organ biopsy specimens were taken before the animals were killed.', 'By 2 hours postshock, 0% immediate resuscitation had an O(2)D increase of 80 mL/kg above end of shock, but O(2)D at 8.4% immediate resuscitation decreased -30 mL/kg, 15% immediate resuscitation fell -65 mL/kg, 30% immediate resuscitation decreased -80 mL/kg below end of shock, and O(2)D with 120% full resuscitation fell to preshock levels. All decreases in O(2)D were significantly (p < 0.05) below end of shock, but both 15% and 30% immediate resuscitation exceeded the 8.4% immediate resuscitation rate (p < 0.05) throughout the resuscitation, and 120% full resuscitation exceeded these (p < 0.05). The immediate resuscitation O(2)D response correlated significantly (p < 0.001) with base deficit and lactate, but blood pressure was not a significant discriminator. Seven-day biopsies showed return of bowel mucosa but a pattern of cellular injury in heart, liver, and kidney that improved from 8.4% < 15% < 30 < 120% immediate resuscitation.",
            "output": [
                "Do oxygen debt criteria quantify the effectiveness of early partial resuscitation after hypovolemic hemorrhagic shock?"
            ]
        },
        {
            "id": "task847-25ff1590705a45c3b11db6b6fdf467a6",
            "input": "All treatment in Crohn's disease, although palliative, aims at restoring full health. The objective of this study was to compare health-related quality of life and psychosocial conditions in patients with Crohn's proctocolitis with a general population.\", \"One hundred and twenty-seven patients with Crohn's proctocolitis (median age 44 years, 44.1% men) were compared with 266 controls (median age 45 years, 50.7% men). A questionnaire consisting of the Short Form-36 (SF-36), the Psychological General Well-Being Index (PGWB) and a visual analogue scale (VAS) evaluating general health as well as questions regarding psychosocial conditions was used. Disease activity was evaluated by Best's modification of the classical Crohn's Disease Activity Index.\", 'Patients in remission had a health related quality of life similar to controls according to the SF-36 apart from general health where scores were lower (P < 0.01). Patients with active disease scored lower in all aspects of the SF-36 (P < 0.001 or P < 0.0001) as well as the PGWB (P < 0.0001). In a model for multiple regression including age, gender, concomitant small bowel disease, permanent stoma, previous colonic surgery, disease activity, duration, and aggressiveness, disease activity was the only variable negatively predicting all 8 domains of the SF-36 in the patient group (P < 0.001). The mean annual sick-leave for patients and controls were 33.9 and 9.5 days (P < 0.0001), respectively. Sixty-eight percent of the patients and 78.4% of the controls (P = 0.04) were married or cohabited, 67.7% and 78.0% (P = 0.04), respectively, had children.",
            "output": [
                "Does health related quality of life in Crohn 's proctocolitis differ from a general population when in remission?"
            ]
        },
        {
            "id": "task847-1a9042646bfe422e83aa8a29cb9c4a33",
            "input": "The ubiquitin proteasome system (UPS) mediates regulated protein degradation and provides a mechanism for closely controlling protein abundance in spatially restricted domains within cells. We hypothesized that the UPS may acutely determine the local concentration of key regulatory proteins at neuronal synapses as a means for locally modulating synaptic efficacy and the strength of neurotransmission communication.', 'We investigated this hypothesis at the Drosophila neuromuscular synapse by using an array of genetic and pharmacological tools. This study demonstrates that UPS components are present in presynaptic boutons and that the UPS functions locally in the presynaptic compartment to rapidly eliminate a conditional transgenic reporter of proteasome activity. We assayed a panel of synaptic proteins to determine whether the UPS acutely regulates the local abundance of native synaptic targets. Both acute pharmacological inhibition of the proteasome (<1 hr) and targeted genetic perturbation of proteasome function in the presynaptic neuron cause the specific accumulation of the essential synaptic vesicle-priming protein DUNC-13. Most importantly, acute pharmacological inhibition of the proteasome (<1 hr) causes a rapid strengthening of neurotransmission (an approximately 50% increase in evoked amplitude) because of increased presynaptic efficacy. The proteasome-dependent regulation of presynaptic protein abundance, both of the exogenous reporter and native DUNC-13, and the modulation of presynaptic neurotransmitter release occur on an intermediate, rapid (tens of minutes) timescale.",
            "output": [
                "Does the ubiquitin proteasome system acutely regulate presynaptic protein turnover and synaptic efficacy?"
            ]
        },
        {
            "id": "task847-7f9776f6d3524185b110dbb0336a820d",
            "input": "Long-lasting forms of synaptic plasticity have been shown to depend on changes in gene expression. Although many studies have focused on the regulation of transcription and translation during learning-related synaptic plasticity, regulated protein degradation provides another common means of altering the macromolecular composition of cells.', 'We have investigated the role of the ubiquitin proteasome system in long-lasting forms of learning-related plasticity in Aplysia sensory-motor synapses. We find that inhibition of the proteasome produces a long-lasting (24 hr) increase in synaptic strength between sensory and motor neurons and that it dramatically enhances serotonin-induced long-term facilitation. The increase in synaptic strength produced by proteasome inhibitors is dependent on translation but not transcription. In addition to the increase in synaptic strength, proteasome inhibition leads to an increase in the number of synaptic contacts formed between the sensory and motor neurons. Blockade of the proteasome in isolated postsynaptic motor neurons produces an increase in the glutamate-evoked postsynaptic potential, and blockade of the proteasome in the isolated presynaptic sensory cells produces increases in neurite length and branching.",
            "output": [
                "Does the ubiquitin proteasome system function as an inhibitory constraint on synaptic strengthening?"
            ]
        },
        {
            "id": "task847-277dd1405d9b4ca18de6869177c3eebe",
            "input": "Oral tacrolimus, approved for the prophylaxis of organ rejection in liver or kidney transplants, has been reported to be effective in anecdotal cases of refractory inflammatory bowel disease.', 'To evaluate the usefulness of low-dose oral tacrolimus in refractory inflammatory bowel disease.', \"Thirty-one adult Caucasian patients with steroid-dependent (n = 15) or steroid-refractory (n = 16) inflammatory bowel disease (Crohn's disease, n = 6; ulcerative colitis, n = 23; pouchitis, n = 2) were enrolled. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in 30 patients and initially intravenously in one patient (0.01 mg/kg body weight per day), aiming for serum trough levels of 4-6 ng/mL. The median treatment duration was 12 months (range, 1-137 months).\", \"Twenty-eight patients (90.3%) experienced a clinical and laboratory response and 20 (64.5%) went into remission. One ulcerative colitis patient and two Crohn's disease patients did not improve. Three ulcerative colitis patients (9.7%) were colectomized at 1, 12 and 24 months after tacrolimus initiation. In 19 of 23 patients (82.6%) taking steroids, steroids were reduced or discontinued. Side-effects included a temporary rise of creatinine (n = 3, 9.7%), tremor or paraesthesias (n = 3, 9.7%), hyperkalaemia (n = 1, 3.2%), hypertension (n = 1, 3.2%) and an opportunistic infection (n = 1, 3.2%).",
            "output": [
                "Is rescue therapy with tacrolimus effective in patients with severe and refractory inflammatory bowel disease?"
            ]
        },
        {
            "id": "task847-016eeeb5f48c4b6d9878bed5d204a5e5",
            "input": "An alteration in the expression of and response to transforming growth factor-beta 1 (TGF-beta 1) appears to be an important event during colorectal carcinogenesis. However, the precise role of TGF-beta 1 in colorectal carcinogenesis is not clear. We have previously described in detail the changes in cell proliferation and differentiation caused by chronic exposure to TGF-beta 1. In this study we sought to better characterize the changes in tumor cell-cell matrix interactions seen during TGF-beta 1-mediated intestinal transformation.', 'Rat intestinal epithelial cells (RIE) and RIE cells transformed by chronic exposure to TGF-beta 1 (RIE-Tr) were treated with TGF-beta 1 and production of components of the plasmin/plasminogen system measured by ELISA and Western blotting. TGF-beta 1 effects on invasion and adhesion were determined in vitro. The role of urokinase on TGF-beta 1-mediated invasion and adhesion were determined using immunoneutralization. The role of COX-2 was determined using a specific COS-2 inhibitor.', 'TGF-beta 1 had no effect on RIE-1 adhesion to collagen types I and IV, fibronectin, and laminin, or invasion through collagen types I and IV. However, 5 ng/mL TGF-beta 1 significantly increased the invasiveness and decreased the adhesiveness of RIE-Tr. This effect of TGF-beta 1 on RIE-Tr was associated with a significant increase in plasmin activity secondary to increased expression of uPA. TGF-beta 1 had no effect on either uPA receptor or PAI-1 in this system. Antibodies to uPA completely blocked the TGF-beta 1-mediated invasiveness of the RIE-Tr cells and returned their adhesiveness to basement membrane proteins to baseline. Addition of the selective Cox-2 inhibitor SC-58125 resulted in a dose-dependent decrease in TGF-beta 1-mediated invasion and uPA expression.",
            "output": [
                "Does intestinal transformation result in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions?"
            ]
        },
        {
            "id": "task847-681d03c1b1fa452c98a7ef7d9acf91c8",
            "input": "Increased systemic levels of inflammatory mediators are seen after open abdominal operations. Macrophages that are exposed to lipopolysaccharide secrete cytokines. Peritoneal macrophages normally reside in a pO(2) of 40 mm Hg. We hypothesize that exposure of lipopolysaccharide-stimulated macrophages to \"non-physiologic\" pO(2) augments cytokine secretion.', 'Murine macrophages were preconditioned to a pO(2) of 40 mm Hg for 24 hours. The medium then was discarded and exchanged for a medium containing a pO(2) of 40, 150, or 440 mm Hg. Macrophages were incubated in the desired pO(2) for 6 and 24 hours while stimulated with lipopolysaccharide (0 to 100 ng/mL). The effect of pO(2) was compared. Supernatant tumor necrosis factor (TNF) and interleukin-6 were measured with enzyme-linked immunosorbent assay. Statistics were performed with analysis of variance.', 'We found dose-dependent lipopolysaccharide-stimulated TNF and interleukin-6 production with macrophages incubated at physiologic pO(2). Higher pO(2) did not stimulate TNF and interleukin-6 in the absence of lipopolysaccharide. However, a pO(2) of 150 and 440 mm Hg significantly (P <.05) increased lipopolysaccharide-stimulated TNF and interleukin-6 production versus 45 mm Hg.",
            "output": [
                "Does relative hyperoxia augment lipopolysaccharide-stimulated cytokine secretion by murine macrophages?"
            ]
        },
        {
            "id": "task847-1dc8f67a2bd049768a101d23d3e67104",
            "input": "Bronchial asthma is characterized by infiltration of eosinophils and other inflammatory cells into the airways. Binding to adhesion molecules expressed on endothelial cells is an initial step of eosinophil accumulation in the airways of asthmatic patients. Theophylline has been widely used in the treatment of bronchial asthma mainly due to its bronchodilating effect. It has recently been suggested that theophylline induces modulating effects on the survival or functional status of eosinophils. The objective of this study was to determine whether theophylline modifies the adhesive interaction between eosinophils and endothelial cells.', 'Eosinophils were isolated from blood of patients with mild asthma. The effects of theophylline on eosinophil adhesion to human umbilical vein endothelial cells (HUVEC) or recombinant adhesion proteins were evaluated. The effect of theophylline on the expression of adhesion molecules on HUVEC was also examined.', \"Theophylline significantly inhibited the eosinophil adhesion induced by formyl-methionyl-leucil-phenylalanine (FMLP) or interleukine-5 (IL-5) at a concentration within the therapeutic range. The effect of theophylline on eosinophil adhesion was mimicked by rolipram, a selective phosphodiesterase inhibitor, and N6,2'-O-dibutyladenosine 3'5'-cyclic monophosphate (Db-cAMP; cAMP analogue). Finally, theophylline inhibited the expression of ICAM-1 and VCAM-1 on HUVEC stimulated with IL-4 plus TNF-alpha.",
            "output": [
                "Does theophylline attenuate the adhesion of eosinophils to endothelial cells?"
            ]
        },
        {
            "id": "task847-d35fec68863d44d1bcde62f26878c85a",
            "input": "The regulatory mechanisms of IL-5 gene transcription in human peripheral T cells are unclear because the transfection efficiency of plasmid constructs into nontransformed T cells is very low.', 'Concanavalin A (ConA)-stimulated blastocytes derived from peripheral blood lymphocytes of asthmatic subjects were transiently transfected with the human IL-5 gene promoter/enhancer-luciferase gene construct, pIL-5 (-511)Luc, and cultured with THP-1 cells (human monocytoid cells) and anti-CD3 monoclonal antibody (mAb). IL-5 level in the culture medium was determined by an enzyme-linked immunosorbent assay. Transcriptional activity of the IL-5 gene was measured by luciferase reporter analysis.', \"ConA-blast lymphocytes of asthmatic patients produced a significant amount of IL-5 upon combined stimulation with anti-CD3 mAb and THP-1 cells, but not with anti-CD3 mAb alone. Costimulation with anti-CD28 mAb also enhanced the anti-CD3 mAb- induced IL-5 production. Accordingly, luciferase activity induced by anti-CD3 mAb stimulation in pIL-5(-511)Luc-transfected ConA-blast lymphocytes was increased 1.9- and 3.4-fold by the addition of anti-CD28 mAb and THP-1 cells, respectively. Serial 5' deletion analysis of the reporter gene demonstrated that the cis-regulatory element located at -119 to -80 is critical for anti-CD3 mAb-induced IL-5 gene transcription.",
            "output": [
                "Does interaction with monocytes enhance IL-5 gene transcription in peripheral T cells of asthmatic patients?"
            ]
        },
        {
            "id": "task847-36c58389b46b40748e3b10309a476463",
            "input": "Platelet-activating factor (PAF) is a potent stimulator of eosinophils. Recently, treatment with a protein kinase C (PKC) inhibitor which generally inhibits PKC isoforms has been shown to modulate several eosinophil functions in distinct manners, in that PKC inhibition enhanced CD11b expression and cellular adhesion, but inhibited superoxide generation and degranulation in PAF-stimulated human eosinophils. These results suggested that distinct PKC isoforms were likely to be involved in each eosinophil function induced by PAF. We have therefore investigated whether or not the PKC isoforms involved in PAF-induced CD11b expression and superoxide generation were different.', 'Human eosinophils prepared from healthy volunteers were treated with PKC inhibitors, bis-indolylmaleimide I (BisI; a general PKC inhibitor), myristoylated PKC inhibitor peptide (myr-psiPKC; a PKCalpha, beta and delta inhibitor) and rottlerin (a PKCdelta inhibitor), followed by stimulation with PAF. CD11b expression was determined using flow cytometry and superoxide generation was evaluated using a cytochrome c reduction assay.', 'BisI treatment led to enhancement of PAF-induced CD11b expression, while myr-psiPKC and rottlerin did not. In contrast, PAF-induced superoxide generation was inhibited by treatment with BisI, myr-psiPKC and rottlerin.",
            "output": [
                "Are distinct isoforms of protein kinase C involved in human eosinophil functions induced by platelet-activating factor?"
            ]
        },
        {
            "id": "task847-a2d433fd24654fb992449480fba73968",
            "input": "Conditioned place aversion (CPA) is known to be a sensitive measure of the aversive motivational state produced by opioid withdrawal in rats made chronically dependent on opioids.', 'The purpose of the present study was to examine the sensitivity of the CPA model in detecting a possible aversive state associated with naloxone-precipitated withdrawal from acute treatment with morphine.', 'Doses of morphine and naloxone, as well as number of conditioning trials, were systematically varied to determine the minimum conditions that would result in a detectable CPA in male Wistar rats. Naloxone (0.003-16.7 mg/kg) was administered 4 h after an injection of vehicle or morphine (1.0, 3.3, or 5.6 mg/kg) and immediately prior to confinement to one compartment of the conditioning apparatus; rats received either one or two such naloxone-conditioning trials (separate by 48 h).', 'Morphine (5.6 mg/kg) followed 4 h later by vehicle produced no significant preference or aversion. In morphine-naive rats, 10 mg/kg naloxone was required to produce a significant CPA with two cycles of conditioning. When increasing doses of morphine were administered (1.0, 3.3, 5.6 mg/kg), significant increases in naloxone potency to elicit a CPA were observed (16-, 211-, and 1018-fold potency shifts, respectively). Naloxone potency after two pretreatments with 5.6 mg/kg morphine was comparable to its potency to elicit a CPA after chronic exposure to morphine. Although naloxone was still effective in producing a CPA after a single conditioning cycle (and hence a single morphine exposure), its effects were dramatically reduced relative to those seen with two conditioning cycles.",
            "output": [
                "Is conditioned place aversion a highly sensitive index of acute opioid dependence and withdrawal?"
            ]
        },
        {
            "id": "task847-ea75f20a2fab411e82e4461be2ecc426",
            "input": "Because clinical diagnosis is inaccurate, objective testing is usually considered necessary when patients present with suspected deep venous thrombosis (DVT).', 'To determine whether a negative result on a quantitative latex D dimer assay eliminates the need for further investigation in patients with a low or moderate pretest probability of DVT.', 'Prospective cohort study.', 'Three tertiary care hospitals in Canada.', '556 consecutive outpatients with suspected first DVT.', 'Patients were categorized as having a low, moderate, or high pretest probability of DVT and then underwent D-dimer testing. Patients with low or moderate pretest probability and a negative D-dimer result had no further diagnostic testing and received no anticoagulant therapy. Serial compression ultrasonography was performed in all other patients. Patients who did not receive a diagnosis of DVT were followed for symptomatic venous thromboembolism.', 'Objectively confirmed symptomatic venous thromboembolic events during 3 months of follow-up.', '283 patients (51%) had low or moderate pretest probability and a negative D-dimer result. One of these patients had DVT during follow-up (negative likelihood ratio, 0.05 [CI, 0.01 to 0.23]). The negative likelihood ratio of the d -dimer test in all patients was 0.03 (CI, 0.01 to 0.16).",
            "output": [
                "Does a diagnostic strategy involving a quantitative latex D-dimer assay reliably exclude deep venous thrombosis?"
            ]
        },
        {
            "id": "task847-41ac700afca049739cc2076e5578c71a",
            "input": "Evacuation disorders associated with a rectocele can be improved by rectocele repair. This study investigated whether anorectal function tests results change after rectocele repair.', 'Fourteen patients with 2nd or 3rd degree rectocele and evacuation disorder were treated by posterior colporrhaphy and evaluated pre- and postoperatively (after 8 months, range 3-14) using questionnaires, anal manometry and endosonography, rectal barostat testing, and colonic transit time measurement with radio-opaque markers. Results from female controls were used for comparison.', 'Preoperatively, rectocele patients had high maximal basal sphincter pressures, large sphincter lengths, and low maximal squeeze pressures, with an anal sphincter defect in seven and lower visceral sensitivity scores than in controls. Postprandial rectal responses (more than 10% decrease in postprandial volume after 1 h) were found in 3 of 14 patients compared to 2 of 11 parous and 9 of 11 nulliparous controls. After repair, a rectocele of 2nd degree was found in four patients. Questionnaire scores were significantly decreased for straining, evacuation disorder, manual support, and protrusion. Overall patient satisfaction with the operation scored 8.25 (range 3-10). Defecation frequencies and stool consistencies were unaltered. Anal pressures, rectal compliance-curves, visceral sensitivity, and colonic transit times were unaltered after the rectocele repair.",
            "output": [
                "Does rectocele repair improve evacuation and prolapse complaints independent of anorectal function and colonic transit time?"
            ]
        },
        {
            "id": "task847-68bcc9c401db4018ad7a6fb1e587a586",
            "input": "The importance of angiogenesis in melanoma has been controversial and is not homogeneous. Mast cell density (MCD) is highly correlated with the extent of both normal and pathological angiogenesis, such as that in chronic inflammatory diseases and tumours.', 'We evaluated the prognostic significance of tumour microvascular density (MVD) and MCD in 25 advanced melanoma patients after resection and a 4-5-year follow up: 48% of the patients were alive and free of metastases (good prognostic subgroup); 16% had developed regional nodal metastases (intermediate prognostic subgroup); and 36% had died (poor prognostic subgroup). Tissues samples were investigated immunohistochemically to count microvessels and mast cells with an antifactor VIII and an antitryptase antibody, respectively.', 'Immunohistological staining showed a higher number of microvessels and mast cells in melanoma lesions of poor prognosis as compared with intermediate prognosis and with good prognosis, respectively.",
            "output": [
                "Do tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma?"
            ]
        },
        {
            "id": "task847-dab1a25d529146fea7f6949918dddeee",
            "input": "To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor beta1 (TGFbeta1), and to explore the mechanism of the protective action of rhein on endothelial cells.', 'A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFbeta1 was determined by immunoprecipitation analysis and western blot.', 'TGFbeta1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFbeta1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFbeta1 in human endothelial cells.",
            "output": [
                "Does rhein inhibit transforming growth factor beta1 induced plasminogen activator inhibitor-1 in endothelial cells?"
            ]
        },
        {
            "id": "task847-39ff083b422a46ccb373ae98f9943a74",
            "input": "Paired electrical stimulation and postextrasystolic potentiation (PESP) of contractility has been extensively studied in ventricular myocardium, but less is known about PESP of atrial contractility. Our aim was to determine whether PESP of atrial contractility could augment left ventricular (LV) preload and improve LV systolic performance.', 'A paired electrical stimulus closely following the pacing stimulus was applied to isolated atrial and ventricular myocardium from 4 dog hearts, and the interval dependent force potentiation was examined. In isolated atrial myocardium, paired pacing increased the active tension from a baseline of 1.36 +/- 0.23 to 2.60 +/- 0.57 g/mm(2); in ventricular myocardium active tension increased from 2.58 +/- 0.42 to 3.81 +/- 0.27 g/mm(2) (both P <.01). Then, LV pressure (micromanometer) and segment length (ultrasonic crystals) were measured in the intact hearts of 7 anesthetized dogs in which premature stimuli were applied to the atrium. In intact hearts, paired pacing of the atrium (coupling interval 200 ms) increased LV end-diastolic pressure from 3.8 +/- 1.0 to 6.4 +/- 1.0 mm Hg; systolic pressure increased from 105 +/- 6 to 112 +/- 7 mm Hg (both P <.05). LV pressure-length loop area (regional stroke work) increased 10.5 +/- 0.2%.",
            "output": [
                "Does potentiation of atrial contractility by paired pacing augment ventricular preload and systolic performance?"
            ]
        },
        {
            "id": "task847-f6179eac911044a593b0d8d9351a3d30",
            "input": "Marked variations in the interleukin-4 (IL-4)-producing capacity of basophils can be observed when aliquots from the same cell preparation are kept under different conditions before stimulation. The aim of this study was to identify factors affecting the functional activity of basophils and to determine optimal storage conditions.', 'Healthy blood donors.', 'Aliquots of purified basophils were kept for different time intervals on ice or at 37 degrees C, in buffer or culture medium, respectively. Following subsequent stimulation with anti-IgE, IL-4 release was determined.', 'Upon storage times up to 4 h, basophils produced more IL-4 when kept at 37 degrees C as compared to 4 degrees C. Surprisingly, buffer was superior compared to culture medium for storage. When the storage time was 20 h, IL-4 release was reduced significantly under all conditions studied.",
            "output": [
                "Is interleukin-4 production from human basophils critically dependent on the storage conditions employed prior to stimulation?"
            ]
        },
        {
            "id": "task847-3f378efec06443359371b0ac73c13f29",
            "input": "To determine the regulatory effects of reactive oxygen species (ROS) on the expression by human osteoarthritic chondrocytes of interleukin (IL)-1beta, -6 and -8, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene in response to interleukin (IL)-1beta or lipopolysaccharide (LPS).', 'Human chondrocytes in monolayer culture were incubated for 3 h with ROS generating molecules such as S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 100 microM), 3-morpholinosydnonimine (SIN-1, 100 microM), with chemically synthesised peroxynitrite (ONOO-, 10 microM) or hydrogen peroxide (H2O2, 100 microM). After treatment by ROS, chondrocytes were washed and then cultured for the next 24 h with or without lipopolysaccharide LPS (10 microg/ml) or IL-1beta (1.10(-11) M). IL-1beta, IL-6, IL-8, iNOS and COX-2 gene expression was analysed by real time and quantitative RT PCR. IL-6, IL-8 and prostaglandin (PG) E2 productions were assayed by specific immunoassays. Nitrite was measured in the culture supernatants by the Griess procedure.', 'LPS and IL-1beta stimulated IL-1beta, IL-6, IL-8, iNOS and COX-2 gene expression. SNAP significantly downregulated LPS induced overall gene expressions, whereas SIN-1 had no effect. ONOO- inhibited iNOS and COX-2 gene expression but not that of the cytokine genes. When chondrocytes were incubated with IL-1beta, SIN-1 and ONOO dramatically decreased all gene expressions while SNAP was inefficient. H2O2 treatment inhibited both LPS and IL-1beta induced gene expressions.",
            "output": [
                "Do reactive oxygen species downregulate the expression of pro-inflammatory genes by human chondrocytes?"
            ]
        },
        {
            "id": "task847-6e0e0f28c98e4877934a8ffbab88cd3f",
            "input": "Asthma is an inflammatory disease of the airways and the current focus in managing asthma is the control of inflammation. In this study, we attempted to investigate the anti-asthmatic potential of a plant derived natural compound, luteolin.', 'We used a murine model of airway hyperreactivity, which mimicked some of the characteristic features of asthma. Male BALB/c mice (8-9 weeks) were used for this study.', 'Mice (n = 6) were sensitized by intraperitoneal (i. p.) injection of 10 mg of ovalbumin (OVA) on days 0, 7 and 14 followed by aerosol inhalation (5% OVA) treatments daily beginning from day 19 to day 23. To study its preventive effect, luteolin (0.1, 1.0, and 10 mg/kg body weight; daily) was administered orally during the entire period (0 to 23 day) of sensitization. To study its curative effect, mice were first sensitized and then luteolin (1.0 mg/kg body weight daily) was given orally from day 26 to 32. The airway hyperreactivity, immunoglobulin E (IgE) in the sera, and cytokines (IFN-gamma, IL-4 and IL-5) in the bronchoalveolar lavage fluid (BALF) were measured.', 'Both during sensitization and after sensitization, luteolin, at a dose of 0.1 mg/kg body weight, significantly modulated OVA-induced airway bronchoconstriction and bronchial hyperreactivity (p < 0.05). Luteolin also reduced OVA-specific IgE levels in the sera, increased interferon gamma (IFN-gamma) levels and decreased the interleukin-4 (IL-4) and interleukin-5 (IL-5) levels in the BALF.",
            "output": [
                "Does luteolin alleviate bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice?"
            ]
        },
        {
            "id": "task847-2fabe1d5d6b34b67a4ea05e04db0697b",
            "input": "Prepulse inhibition (PPI) of startle provides an operational measure of sensorimotor gating in which a weak stimulus presented prior to a startling stimulus reduces the startle response. PPI deficits observed in schizophrenia patients can be modeled in rats by individual housing from weaning until adulthood. The deficits in PPI produced by isolation rearing can be reversed by antipsychotics. We previously found that (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole HCl (MKC-242), a highly potent 5-HT(1A) receptor agonist, reduced aggressive behavior selectively in isolation-reared mice.', 'This study examines whether isolation rearing of mice produces PPI deficits and whether PPI deficits are attenuated by 5-HT(1A) receptor activation.', 'Male ddY mice, 4 weeks old, were housed for more than 6 weeks singly or in groups of five or six. The PPI of the acoustic startle response was measured using SR-LAB systems.', 'The PPI was less in isolation-reared mice than in group-reared mice. Oral administration of MKC-242 at 0.1-0.3 mg/kg reversed PPI deficits in isolation-reared mice, although it did not affect PPI in group-reared mice. MKC-242 did not affect MK-801-induced and apomorphine-induced PPI deficits in group-reared mice. The reversal by MKC-242 of isolation-induced PPI deficits was antagonized by the 5-HT(1A) receptor antagonist WAY100635 at low doses.",
            "output": [
                "Does the 5-HT1A receptor agonist MKC-242 reverse isolation rearing-induced deficits of prepulse inhibition in mice?"
            ]
        },
        {
            "id": "task847-e0a7b3f6228240c79599982e2a534f22",
            "input": "To study the healing effect of recombinant human epidermal growth factor (hEGF) on diabetic foot ulcers.', 'A total of 127 consecutive patients were screened and 61 diabetic subjects were recruited into this double-blind randomized controlled study. Predetermined criteria were used for diagnosis and classification of the diabetic wound. The patients were randomized into three groups. All patients attended our Diabetes Ambulatory Care Center every other week for joint consultation with the diabetologist and the podiatrist. Group 1 (control) was treated with Actovegin 5% cream (Actovegin), group 2 with Actovegin plus 0.02% (wt/wt) hEGF, and group 3 with Actovegin plus 0.04% (wt/wt) hEGF. The study end point was the complete closure of the wound. Failure to heal was arbitrarily defined as incomplete healing after 12 weeks.', 'Final data were obtained from 61 patients randomly assigned into three groups. The mean ages of the patients, wound sizes, wound duration, metabolic measurements, and comorbidities were comparable within groups, except that group 3 had more female patients. Mean follow-up for the patients was 24 weeks. Data were cutoff at 12 weeks, and results were analyzed by intention to treat. After 12 weeks, in group 1 (control) eight patients had complete healing, two patients underwent toe amputation, and nine had nonhealing ulcers. In group 2 (0.02% [wt/wt] hEGF) 12 patients experienced wound healing, 2 had toe amputations, and 7 had nonhealing ulcers. Some 20 of 21 patients in group 3 (0.04% [wt/wt] hEGF) showed complete wound healing. Healing rates were 42.10, 57.14, and 95% for the control, 0.02% (wt/wt) hEGF, and 0.04% (wt/wt) hEGF groups, respectively. Kaplan-Meier survival analysis suggested that application of cream with 0.04% (wt/wt) hEGF caused more ulcers to heal by 12 weeks and increased the rate of healing compared with the other treatments (log-rank test, P = 0.0003).",
            "output": [
                "Does human epidermal growth factor enhance healing of diabetic foot ulcers?"
            ]
        },
        {
            "id": "task847-4e0268fff7e74f8791095ef6373a3841",
            "input": "To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospective multicenter trial of diabetic patients with foot ulceration.', 'We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospective, randomized controlled trial.', 'Wound area measurements at baseline and after 4 weeks were performed in 203 patients. The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53%. Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58%, whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9% (P < 0.01). The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers (1.5 vs. 0.8 cm(2), P < 0.02). The percent change in wound area at 4 weeks in those who healed was 82% (95% CI 70-94), whereas in those who failed to heal, the percent change in wound area was 25% (15-35; P < 0.001).",
            "output": [
                "Is percent change in wound area of diabetic foot ulcers over a 4-week period a robust predictor of complete healing in a 12-week prospective trial?"
            ]
        },
        {
            "id": "task847-f4c870600fe6437398c7b59daa5f43b4",
            "input": "This longitudinal study had three aims: 1) determine the extent to which boys at high average risk and low average risk for substance use disorder differ on a construct of neurobehavioral disinhibition, 2) evaluate the capacity of neurobehavioral disinhibition to predict substance use frequency at age 16, and 3) demonstrate the utility of neurobehavioral disinhibition in predicting substance use disorder.', 'The authors derived an index of neurobehavioral disinhibition from measures of affect, behavior, and cognition. The neurobehavioral disinhibition score was used to discriminate youth at high and low average risk for substance use disorder and to predict substance use frequency after 4-6 years and substance use disorder after 7-9 years.', 'The neurobehavioral disorder score significantly discriminated boys at high average risk from those at low average risk at ages 10-12. Neurobehavioral disinhibition at age 16, in conjunction with substance use frequency and risk status group, predicted substance use disorder at age 19 with 85% accuracy and accounted for 50% of the variance in Drug Use Screening Inventory overall problem density score. Neurobehavioral disinhibition was a stronger predictor of substance use disorder (odds ratio=6.83) than substance consumption frequency (odds ratio=3.19).",
            "output": [
                "Does neurobehavioral disinhibition in childhood predict early age at onset of substance use disorder?"
            ]
        },
        {
            "id": "task847-a625db10c0a34158b0a386432218887e",
            "input": "Progression of pulmonary vascular disease limits heart transplantation for hypoplastic left heart syndrome (HLHS) to early infancy. Our objective was to assess the impact of bilateral pulmonary artery banding (PAB) on the operative courses of HLHS infants transplanted at ages older than 4 months.', 'Courses of all HLHS patients in our center who remained listed to age >or=120 days before heart transplantation were assessed. Patients undergoing transplantation after standard management (control group) were compared to patients having a prior pulmonary blood flow limiting procedure (PAB group).', 'Of 16 identified patients, one crossed over to stage I Norwood on day 185 and died post-operatively. Fifteen patients were transplanted at age >or=120 days (control group n=9, PAB group n=6). Four PAB patients had open PA band placement. Two PAB patients underwent experimental percutaneous bilateral internal pulmonary artery flow limiting device insertion. The PAB group mean age at banding was 141+/-54 days, and mean interval from PAB to transplant was 35+/-31 days (range 1.5-68 days). No differences in age at transplant, weight at transplant, warm graft ischemia time or total graft ischemia time were detected between groups. Mean times of mechanical ventilation (control 143+/-69h vs. PAB 44+/-13h), inhaled nitric oxide (control 126+/-70h vs. PAB 37+/-9h), inotropic support (control 171+/-64h vs. PAB 87+/-17h), intensive care unit (ICU) stay (control 8.3+/-2.7 days vs. PAB 4.5+/-1.4 days), and hospital stay (control 10.4+/-3.9 days vs. PAB 7.0+/-1.1 days) were all lower in the PAB group (P<0.05 all comparisons). Two control patients died, three required extracorporeal membrane oxygenation (ECMO), and six did not tolerate primary chest closure. No PAB patient died or required ECMO. All PAB patients tolerated primary chest closure. All PAB patients had widely patent branch pulmonary arteries with no re-interventions to date. All hospital survivors remain alive (mean follow-up, control 50.2 months, PAB 11.5 months).",
            "output": [
                "Does mechanical limitation of pulmonary blood flow facilitate heart transplantation in older infants with hypoplastic left heart syndrome?"
            ]
        },
        {
            "id": "task847-d0de4384b5c7462e9eb6236b01ed6304",
            "input": "Device-related infections remain a considerable problem of left-ventricular support. We compared the device-related-infections between the HeartMate left ventricular assist device (LVAD) and the Jarvik 2000 permanent LVAD, a device with a novel retroauricular power-supply.', 'Between December 2000 and September 2002 we implanted the HeartMate-vented, electrical-system in 11 patients and the permanent Jarvik 2000 in six patients. Total support time was 1626 patient-days (HeartMate, 26-271 days) versus 1246 patient-days (Jarvik 2000, 8-411 days). As potential risk factors for infection we analyzed age, preoperative hospital-days, total protein, cardiac index, maximal oxygen uptake, use of inotropes, LVAD risk-score-index and Aaronson-Mancini-score, intubation time, and intensive care unit stay. We used the Center of Disease Control definitions for surgical site infections.', 'HeartMate-patients were younger than Jarvik 2000 patients (46+/-13 versus 58+/-6 years, P=0.056), there were no other differences in the risk factors. Four HeartMate-patients needed late (>or=48 h) surgical revisions for bleeding/hematomas versus no revisions in the Jarvik 2000 patients. In the HeartMate-patients, there were seven (64%) driveline-infections, five (45%) device-pocket infections, and three (27%) bloodstream-infections, or 0.43 device-related infections/100 patient-days. Infections occurred early (34+/-31 days). Three patients required urgent transplantation due to bloodstream infection. There were no adverse outcomes in the HeartMate-group due to infection. In the Jarvik 2000 patients, there was one driveline-infection (16%) after 270 days of support (0.08 device-related infections/100 patient-days), significantly less than in the HeartMate-group (P=0.044). Driveline infections resolved with antibiotics and local wound care in the Jarvik 2000 patient, but only in one of seven HeartMate-patients.",
            "output": [
                "Is the Jarvik 2000 associated with less infections than the HeartMate left ventricular assist device?"
            ]
        },
        {
            "id": "task847-1bda87bd0dfc48e2b0deed53176e7440",
            "input": "To study the effect of removal of YY1 binding sites within the LCR region of HPV 16 on viral transforming activity.', 'Previously we had generated new plasmids carrying HPV 16 whole genome, which contained naturally occurred mutated LCR sequences. The viral transforming abilities on mouse fibroblasts were evaluated in anchorage-independent assays, while the expression and activity of YY1 protein in fibroblasts were tested with EMSA and luciferase assays.', 'YY1 protein was expressed in mouse fibroblasts C127, with ability for DNA binding and repression on P97 activity. Both HPV 16 wild-type DNA and mutated DNAs were transfected into C127 cells and spread to the soft-agarose mediums after selecting with G 418. The growth numbers of the cells transfected with mutated HPV 16 DNAs were 2-10 fold more than that with wild-type HPV 16 DNA.",
            "output": [
                "Does [ Removal of YY1 binding sites in HPV 16 LCR increase viral transforming activities on mouse fibroblasts ]?"
            ]
        },
        {
            "id": "task847-a5d295a0d0b542e8bcef86441e1f5497",
            "input": "To show whether the ratios of squalene and cholesterol precursor sterols to cholesterol and cholestanol and plant sterols to cholesterol change differently in plasma and especially in the red cells of hypercholesterolemic children during consumption of plant stanol and sterol ester spreads.', 'In a randomized, double-blind, crossover study, hypercholesterolemic children (n = 23) consumed low-fat plant stanol and sterol ester spreads for 5-week periods separated by a 5-week washout period. Plasma and red cell lipids, squalene, and noncholesterol sterols were measured before and at the end of each period.', 'The plant stanol and sterol ester spreads lowered plasma total (-9% and -6%, respectively) and low-density lipoprotein (-12% and -9%) cholesterol but had no effect on red cell cholesterol, high-density lipoprotein cholesterol, or plasma triglycerides. The ratios of plasma and red cell sitosterol and campesterol to cholesterol decreased by 32% to 36% (P <.001) with the plant stanol ester and increased by 40% to 52% (P <.001) with the sterol ester spread.",
            "output": [
                "Are red cell and plasma plant sterols related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia?"
            ]
        },
        {
            "id": "task847-a07cf410699c4ee79cdf56124f8902fa",
            "input": "Nitric oxide (NO) and its role in surgical inflammation are well documented; demonstrating the role of NO in necrotizing enterocolitis (NEC) and ways in which it may be suppressed may provide avenues for immune modulation in the treatment of NEC.', 'We sought to demonstrate an increase in inducible nitric oxide synthase (iNOS) mRNA and nitric oxide in an experimental model of necrotizing enterocolitis. In addition, we hypothesized that interleukin-10 (IL-10) would attenuate this response.', \"Newborn rats were treated with 25 microliters intraperitoneal IL-10 or vehicle prior to laparotomy, 1 h superior mesenteric artery (SMA) occlusion, 50 micrograms/kg intraluminal platelet activating factor administration, and SMA reperfusion. iNOS mRNA and nitric oxide levels were measured in the liver, small bowel, and serum and compared using Student's t-test.\", 'Small bowel iNOS mRNA increased after NEC induction from 0.058 +/- 0.02 to 0.144 +/- 0.05 relative intensity units (RIU) at 2 h (p < 0.01) and from 0 to 0.09 +/- 0.02 RIU at 6 h (p < 0.03). Liver mRNA increased from 0.026 +/- 0.002 to 0.485 +/- 0.09 RIU (p < 0.002) and from 0 to 0.069 +/- 0.02 RIU (p < 0.0001) at 2 and 6 h, respectively. Serum nitric oxide increased in NEC induced animals at 2 h from 28.04 +/- 10.5 to 45.18 +/- 6.8 microM (p < 0.001). IL-10 suppressed iNOS mRNA and nitric oxide expression at 2 h in small bowel, liver, and serum by 60%, 89%, and 11%, respectively.",
            "output": [
                "Does interleukin-10 inhibit inducible nitric oxide synthase in an animal model of necrotizing enterocolitis?"
            ]
        },
        {
            "id": "task847-02af262506da4f669947a6191e88e029",
            "input": "To establish a cell model by chronically infecting human gastric epithelial cells with H.pylori, and to determine the effect of chronic H.pylori infection on apoptosis of gastric epithelial cells.', 'Human non-tumor gastric epithelial cells GES-1 were cocultured with an H.pylori strain SS1 for 16 weeks, in order to obtain GES-1 \"model\" cells. Biological characteristics of the model cells including growth, adherence and clone formation were determined. Apoptosis of the \"model\" cells in response to apoptosis inducers such as H.pylori and other enterobacteria and agents commonly used in the chemotherapy of gastric cancer were measured by flow cytometry.', 'A cell model of human gastric epithelial cells with chronic H.pylori infection (GES-1 model cells) was successfully established. Apoptosis was dramatically decreased in the \"model\" cells with and without stimulation by H.pylori and other enterobacteria and some chemotherapeutic agents.",
            "output": [
                "Does [ Chronic Helicobacter pylori infection induce apoptosis-resistance in gastric epithelial cells ]?"
            ]
        },
        {
            "id": "task847-fad85a425d0d4aa29d7e16f3c335cd10",
            "input": "Elevated arterial PCO2 (hypercapnia) is a known risk in diving with closed circuit breathing apparatus. In a retrospective study, we determined CO2 retention and the ability to detect CO2 in novice divers who were either CO2-recognition-trained subjects (TS) or untrained subjects (UTS).', 'Ventilatory and perceptual responses to variations in inspired CO2 (range 0-5.6 kPa, 0-42 mm Hg) during moderate exercise were assessed in novice Israeli Navy divers on active duty. Tests were carried out on 231 TS and 213 UTS.', 'The minimal mean inspired PCO2 that could be detected was 4.8 +/- 1.6 kPa (36 +/- 12 mm Hg) in UTS and 2.9 +/- 0.7 kPa (22 +/- 5 mm Hg) in TS (p < 0.0001). No significant changes were found in PETCO2 between the two groups during exposure to a PICO2 of 5.6 kPa (42 mm Hg). There were 46 TS who were found to be CO2 retainers (more than +1 SD above the mean) and 19 were classified as poor detectors (more than +1 SD above the mean). Seven subjects exhibited both traits. During actual oxygen diving performed later by this group, the only four cases of CNS-oxygen toxicity were among those seven subjects (p < 0.01).",
            "output": [
                "Does training improve divers ' ability to detect increased CO2?"
            ]
        },
        {
            "id": "task847-00efe2ff3ccc4832a2d19c0242f65865",
            "input": "Food atopy patch tests (APTs) are considered a useful tool for the diagnosis of food allergy. Hypersensitivity to peanuts has not been investigated by means of APTs so far.', 'APTs and skin prick tests (SPTs) with peanuts were performed in 136 atopic dermatitis (AD) patients. Relevance of positive and negative responses to these tests was assessed by repeated open challenges with peanuts.', 'Nine percent of our AD patients reacted to the challenge. Positive responses to APTs were recorded in 19% of the patients, whereas in 12% positive SPTs were observed. APTs were more frequently positive in subjects with eczematous responses after challenge with respect to those with urticarial reactions. SPT reactivity proved to be higher in patients above 12 years of age, whereas APT positivity was more frequent in children under 6 years. APT sensitivity proved significantly higher than SPT sensitivity, in particular in children under 12 years of age. On the contrary, SPT specificity and positive predictive value were significantly higher with respect to those of APT in the age group of subjects under 6 years of age.",
            "output": [
                "Does combined skin prick and patch testing enhance identification of peanut-allergic patients with atopic dermatitis?"
            ]
        },
        {
            "id": "task847-1886a1ce757442c5a242f4b5a7faa55a",
            "input": "Cell-to-cell interaction is thought to be an important feature of a variety of biological processes. As far as the proinflammatory process is concerned, the interaction between mesangial cells and monocytes/macrophages induces the expression of monocyte chemoattractant protein-1 (MCP-1), and this may play a role in glomerulonephritis. In this study, we investigated whether the cell-to-cell interaction between immune cells and renal fibroblasts induces MCP-1 gene expression, which may be involved in interstitial inflammation in the kidney.', 'Human renal fibroblast cell lines, tNKF (from a normal kidney) and tFKIF (from a kidney with fibrosis), and peripheral blood mononuclear cells (PBMC) were used to assess the effect of cell-to-cell contact on the expression of MCP-1 mRNA in the fibroblasts. The expression of the MCP-1 gene in the fibroblasts was also examined after stimulation with tumor necrosis factor-alpha (TNF-alpha) and the culture supernatant from PBMC. RT-PCR was used to detect MCP-1 mRNA expression. Neutralizing antibodies to intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial adhesion molecule-1 (VCAM-1) were used to block the cell-to-cell contact between the fibroblasts and PBMC.', 'TNF-alpha and the culture supernatant from PBMC increased MCP-1 gene expression in tNKF cells. Contact culture with PBMC also significantly increased MCP-1 gene expression in tNKF cells. Although the basal level of MCP-1 mRNA was higher in tFKIF than tNKF cells, tFKIF cells did not respond significantly to any stimulation in this study. Following pretreatment with anti-ICAM-1 antibody, MCP-1 gene expression in tNKF cells was significantly suppressed in contact culture with PBMC. Anti-VCAM-1 antibody treatment had no effects.",
            "output": [
                "Does direct contact between human peripheral blood mononuclear cells and renal fibroblasts facilitate the expression of monocyte chemoattractant protein-1?"
            ]
        },
        {
            "id": "task847-ba46f22c68c846da8f6d590c29948b53",
            "input": "The protective functions of oestrogen therapy alone on cardiovascular risk parameters are well established; however, the action of progesterone on vascular parameters in an oestrogen-deprived environment is less clear.', 'To examine the effects of progesterone alone on vascular function and hormone levels in postmenopausal women.', 'In a randomized, double-blind, cross-over design study, 20 healthy postmenopausal women were tested before and after 6 weeks of treatment with micronized progesterone (100 mg/daily) and matching placebo.', 'Tests included measurement of sex hormones and gonadatropin levels, lipids and measures of surrogate markers of vascular function including, blood pressure, flow-mediated dilation of the brachial artery, systemic arterial compliance and cutaneous vascular reactivity.', 'The mean (+/- SEM) age of subjects was 56.4 +/- 2.7 years and the average body mass index at the baseline visit was 27.1 +/- 1.0 kg/m2. Progesterone levels increased as a result of progesterone treatment (0.9 +/- 0.2 to 9.5 +/- 2.3 nmol/l, P = 0.001), whereas follicle-stimulating hormone levels decreased (75.1 +/- 11.4 to 67.6 +/- 10.0, P = 0.001). Systemic arterial compliance, flow mediated dilation, cutaneous vascular reactivity, blood pressure, body mass index, plasma levels of cholesterol, lipids and oestrogen were unchanged.",
            "output": [
                "Does progesterone influence vascular function in postmenopausal women?"
            ]
        },
        {
            "id": "task847-88eb88d8520f4b70ba9447adc498877a",
            "input": "Serum hepatocyte growth factor (HGF) is associated with blood pressure. We investigated whether the serum HGF level differs between hypertensive and normotensive postmenopausal women (PMW) and whether hormone replacement therapy (HRT) alters the serum HGF level and blood pressure in hypertensive and normotensive PMW.', 'Prospective observational study.', 'A total of 33 PMW with mild to moderate essential hypertension controlled by antihypertensive treatment (mean age, 57 +/- 6 years) and 23 normotensive PMW (mean age, 57 +/- 7 years) received continuous HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) once a day orally for 12 months, and we measured serum HGF levels and blood pressure before and 12 months after the start of HRT.', 'The baseline serum HGF level was significantly higher in hypertensive PMW than in normotensive PMW. HRT significantly decreased the serum HGF level in hypertensive subjects, from 2.85 +/- 0.64 pmol/l to 2.49 +/- 0.65 pmol/l (P < 0.001), but not in normotensive subjects. HRT did not change blood pressure in either group.",
            "output": [
                "Does hormone replacement therapy cause a decrease in hepatocyte growth factor in hypertensive women?"
            ]
        },
        {
            "id": "task847-c717d52eebfc418fb618d086a8bd2e9f",
            "input": "The current study was conducted to examine the effect of red pepper supplementation on cholesteryl ester transfer protein (CETP) activity, along with its anti-atherosclerotic effect in cholesterol-fed rabbits.', 'Rabbits were fed a 1% cholesterol diet for 12 weeks, including a 1% red pepper powder supplement.', 'The red pepper supplemented group exhibited significantly lower CETP activity than the control group during the experimental period (P<0.05). The total cholesterol, triglyceride (TG), LDL-C, VLDL-C, and VLDL-TG levels and atherogenic index (AI) were all significantly lower in the red pepper group than in the control group (P<0.05), whereas the HDL-C level was significantly higher in the red pepper group than in the control group during the experimental period (P<0.05). Furthermore, the red pepper supplementation increased the fecal TG excretion (P<0.05). Based on a morphological examination, the red pepper supplemented group exhibited fewer fat droplet deposits than the control group.",
            "output": [
                "Does red pepper attenuate cholesteryl ester transfer protein activity and atherosclerosis in cholesterol-fed rabbits?"
            ]
        },
        {
            "id": "task847-730ac0bbf49b4615a8e1086561e27d20",
            "input": "Although previous studies have found that electrolytic lesions of the anterior hypothalamic area (AHA) resulted in the suppression of anaphylaxis, their effect on late allergic responses has scarcely been investigated. To clarify the role of the AHA on possible late asthmatic responses, including their neuroendocrinological mechanisms, we examined the effect of electrolytic AHA lesions on antigen-induced eosinophilic infiltration into the airway tract and measured the plasma corticosterone and catecholamine levels in sensitized rats, i.e. a model of bronchial asthma.', 'The rats were randomly divided into 3 groups, including: (1) an unoperated control group; (2) a sham AHA-lesioned group and (3) an AHA-lesioned group. Then, we investigated antigen-induced eosinophilic infiltration into right bronchoalveolar lavage fluid (BALF) and the lamina propria mucosae of the left main bronchus.', 'The AHA-lesioned group showed the significantly lowest number of eosinophils in both the BALF (p < 0.01) and the main bronchus (p < 0.05). The plasma adrenaline levels in the AHA-lesioned group were significantly higher than those in the other groups (p < 0.05). No differences were found in the plasma corticosterone or noradrenaline levels among the 3 groups.",
            "output": [
                "Do anterior hypothalamic lesions inhibit antigen-induced airway eosinophilia in rats?"
            ]
        },
        {
            "id": "task847-024abc41b3dc4b9081e8d6b7aa2f8ccd",
            "input": "The clinical benefit of using reverse transcription polymerase chain reaction (RT-PCR)-based assays to detect circulating tumour cells during post-operative surveillance of cancer patients remains unclear. Cytokeratin 20 has been proposed as a tissue-specific marker for the detection of micrometastases in the blood of colorectal cancer patients. However, recent reports have challenged its specificity, and hence the validity of its use.', 'The aim of this study was to evaluate the tissue-specificity of ck20 mRNA transcription and its use for detecting circulating colon epithelial cells.', 'RNA was isolated from the peripheral blood of 51 colorectal cancer patients, four patients with benign gastrointestinal disease and 42 healthy controls. In addition, it was prepared from 32 colorectal cancers, from a pituitary cancer, from normal kidney, liver, fibroblasts, keratinocytes and from 24 lymph nodes obtained from eight patients with benign gastrointestinal disease. Real-time RT-PCR assays were used to quantitative and compare ck20 transcription.', 'Significant levels of ck20 mRNA were detected in all 42 blood samples from healthy volunteers and in all pre- and post-operative blood samples from colorectal cancer patients regardless of the presence of metastatic disease. It was also detected in all other mRNA samples analysed.",
            "output": [
                "Is cytokeratin 20 a tissue-specific marker for the detection of malignant epithelial cells in the blood of colorectal cancer patients?"
            ]
        },
        {
            "id": "task847-953803755ff549549292ec7de9e74864",
            "input": "Ischemia, such as that caused by a tourniquet, stimulates thromboxane (Tx) A(2) synthesis. TxA(2) might sensitize the operated limb to various complications, such as compartment syndrome and thromboembolic events.', 'We studied the effect of pretreatment with a single dose of acetylsalicylic acid (ASA) (25, 100, and 500 mg) given 3 hours before surgery on the formation of TxB(2), a stable metabolite of TxA(2), after tourniquet deflation in 32 knee or ankle surgery patients.', 'Tourniquet time varied between 60 +/- 8 to 71 +/- 7 (SE) minutes. In control patients without ASA pretreatment, the platelet-produced femoral vein serum TxB(2) concentration over 30 minutes in vitro coagulation increased remarkably (from 40.0 +/- 20 ng/mL to 73.5 +/- 39 ng/mL) immediately after tourniquet deflation. Plasma concentrations increased similarly, approximately threefold. Pretreatment with 100 or 500 mg ASA prevented the increase in TxB(2) concentrations. Radial artery concentrations of TxB(2) were similar to venous concentrations in the different treatment groups.",
            "output": [
                "Does single dose of acetylsalicylic acid prevent thromboxane release after tourniquet ischemia?"
            ]
        },
        {
            "id": "task847-2de9f373e7b948edb4f8c47667ba41fd",
            "input": "Human xenografts in athymic mice are frequently used as preclinical models of cancer to investigate the targeting of drugs. In order to distinguish specific from nonspecific targeting of the xenograft, the mice can be implanted with different malignant cell lines. We studied in xenograft success and growth rates after implantation of human lymphoma and breast cancer cells to begin an assessment of the validity of this approach for distinguishing specific from nonspecific targeting. Investigations were undertaken to determine the effect of two different cell-line xenografts, and prior radiation needed for one of the xenografts, on implantation success and growth rates.', 'Female athymic mice were given 4 Gy of external beam radiation 4 days prior to subcutaneous (s.c.) abdominal implantation of 6 x 10(6) Raji human lymphoma cells. One week later, 3 x 10(6) hamster blood transfusion (HBT) 3477 human breast cancer cells were implanted s.c. in a contralateral abdominal site. Xenografts were evaluated frequently thereafter. Xenograft success and growth rates were compared to those observed in \"historical\" control groups, wherein only a single xenograft of each type was implanted.', 'Raji xenografts developed from 73.7% of the implantations, and 100% of the HBT 3477 xenografts were successful in the experimental group. The \"historical\" Raji xenograft success rate was 74.1% (+/-9.3%), and the \"historical\" HBT 3477 xenografts success rate was 99.0% (+/-1.1%). HBT 3477 xenografts did not affect the growth rate of the Raji xenografts, and the mean doubling time for the experimental Raji xenografts was 6.3 days (+/-4.5 days), compared to the \"historical\" control group mean of 5.1 days (+/-3.9 days; p = 0.2). Similarly, the growth rates for the HBT 3477 xenografts were not affected by the Raji xenografts and the pre-radiation needed for this model. Mean doubling time for HBT 3477 xenografts in the presence of Raji xenografts was 9.2 days (+/-17.6 days), compared to a doubling time of 1.4 days (+/-15.2 days; p = 0.55 and 0.94 studies 1 and 2, respectively). Mean HBT 3477 xenograft doubling time for the \"historical\" control group was 4.4 days (+/-6.0 days).",
            "output": [
                "Does implantation of different malignant human cell lines in an athymic mouse alter success and growth rates of either xenograft?"
            ]
        },
        {
            "id": "task847-62d2c63112ab4aea91c0335c8ab35a02",
            "input": "Accumulating evidence from observational studies indicates that a high calcium intake may reduce body weight and body fat. However, few randomized trials have been conducted.', 'We examined whether calcium supplementation affects body weight and body fat in young girls and whether a relation exists between habitual calcium intake and body weight and body fat.', 'A randomized, double-blind, placebo-controlled intervention study was conducted in 110 young girls. The subjects were randomly assigned to receive 500 mg Ca/d as calcium carbonate or placebo for 1 y. Two groups of girls were selected according to habitual calcium intake from a large group; one group consumed 1000-1304 mg/d (40th-60th percentile; n = 60) and the other group consumed <713 mg/d (<20th percentile; n = 50). Height, body weight, body fat, and calcium intake were measured at baseline and after 1 y.', 'At baseline a significant negative correlation was observed between habitual dietary calcium intake and percentage of body fat (r = -0.242, P = 0.011). However, calcium supplementation had no effect on height, body weight, or percentage body fat.",
            "output": [
                "Does calcium supplementation for 1 y reduce body weight or fat mass in young girls?"
            ]
        },
        {
            "id": "task847-95471ac7a4a742fdae7706093697a7d5",
            "input": "The pathogenesis of pruritus in renal disease is not yet understood. Evidence suggests that mast cells play a role; for example, the number of dermal mast cells is increased in patients on hemodialysis.', 'To investigate a possible role of mast cell tryptase in pruritus of patients undergoing chronic hemodialysis, serum mast cell tryptase concentrations were measured in blood samples taken from 93 such patients, 53 of whom also recorded the severity of their pruritus on a visual analogue scale.', 'Serum mast cell tryptase levels were above 11.4 microg/l (95th percentile) in 84 of 93 hemodialysis patients (90.3 %). The intensity of pruritus correlated significantly (p = 0.014) with the tryptase levels, an associated not yet shown for other mast cell-related parameters.",
            "output": [
                "Are baseline serum levels of mast cell tryptase raised in hemodialysis patients and associated with severity of pruritus?"
            ]
        },
        {
            "id": "task847-016689d625e94d82a55cdd15d369bf7f",
            "input": "Although N(2)O has been widely used as an anaesthetic adjuvant its effect on electroencephalographic (EEG) activity is poorly understood because it is usually studied in the presence of additional anaesthetics, including inhaled anaesthetics. We examined the EEG effects of N(2)O in rats using a hyperbaric chamber that permitted N(2)O to be the sole anaesthetic.', 'Rats (n=10) were anaesthetized with isoflurane and EEG activity was recorded from skull screws. The rats were placed into a hyperbaric chamber and mechanically ventilated. Isoflurane was eliminated while the chamber was pressurized with N(2)O. The minimum alveolar concentration (MAC) was determined in five rats by adjusting the chamber pressure and N(2)O concentration, and applying a tetanic noxious stimulus to the tail via an electrical pass-through. EEG responses to noxious stimulation (20 electrical pulses at 40 V applied to the tail at 0.1, 1 and 3 Hz, and 50 Hz tetanic stimulation at 60 mA applied for 30 s) were determined at 1.5 and 2 atm N(2)O.', 'The N(2)O MAC was 1.7+/-0.1 atm. No consistent EEG activation occurred during electrical stimulation at either partial pressure of N(2)O, although spontaneous EEG activation often occurred. Blood pressure increased after the 3 and 50 Hz stimuli. Four other rats anaesthetized with isoflurane had EEG activation with the 3 and 50 Hz stimuli.",
            "output": [
                "Does nitrous oxide depress electroencephalographic responses to repetitive noxious stimulation in the rat?"
            ]
        },
        {
            "id": "task847-4ef41c18edc442fb8a1f120cc3ec948d",
            "input": "Matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) play a key role in tissue remodelling after processes such as joint destruction in rheumatoid arthritis. Their expression may reflect the disease activity and they could therefore represent a useful marker to assess the efficacy of therapy. In this study MMP-2 and MMP-9 serum were evaluated in patients with chronic arthritis during therapy with the anti-TNFalpha mAb, infliximab.', 'Fifty patients with chronic arthritis, 26 with rheumatoid arthritis and 24 with undifferentiated chronic arthritis, were recruited and treated with infliximab (3 mg/kg). Serum concentrations of MMP-2 and MMP-9 were serially measured by gelatine zymography at baseline and after two and fourteen weeks of infliximab therapy. DAS-28 and ACR response criteria were applied to assess disease activity and clinical improvement. Twenty-four healthy donors were included in the study as controls.', 'Although therapy with infliximab induced a statistically significant reduction of the DAS-28 score and improvement of the ACR clinical response, MMP-2 and MMP-9 serum concentrations were not modulated during therapy with infliximab.",
            "output": [
                "Does infliximab therapy modify MMP-2 and MMP-9 serum concentrations in chronic arthritis?"
            ]
        },
        {
            "id": "task847-3c9ca8cac5394b919f1be3eb059aa1e0",
            "input": "To examine whether anemia is associated with a higher incidence of recurrent falls.', 'Prospective cohort study.', 'Community-dwelling sample in The Netherlands.', 'Three hundred ninety-four participants aged 65 to 88 from the Longitudinal Aging Study Amsterdam.', 'Anemia was defined according to World Health Organization criteria as a hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men. Falls were prospectively determined using fall calendars that participants filled out weekly for 3 years. Recurrent fallers were identified as those who fell at least two times within 6 months during the 3-year follow-up.', 'Of the 394 persons, 11.9% (18 women and 29 men) had anemia. The incidence of recurrent falls was 38.3% of anemic persons versus 19.6% of nonanemic persons (P=.004). After adjustment for sex, age, body mass index, and diseases, anemia was significantly associated with a 1.91 times greater risk for recurrent falls (95% confidence interval=1.09-3.36). Poor physical function (indicated by muscle strength, physical performance, and limitations) partly mediated the association between anemia and incidence of recurrent falls.",
            "output": [
                "Is late-life anemia associated with increased risk of recurrent falls?"
            ]
        },
        {
            "id": "task847-6259f68b532d42d79c8332d9bfed1e02",
            "input": "To examine the individual and combined influence of body mass index (BMI) and waist circumference (WC) on mortality risk in older people.', 'Longitudinal cohort study.', 'Cardiovascular Health Study, a longitudinal study of cardiovascular disease and its risk factors in older people.', 'Five thousand two hundred men and women aged 65 and older.', 'BMI and WC were measured at baseline. The risks of all-cause mortality associated with BMI and WC were examined using Cox proportional hazards models over 9 years of follow-up.', 'When examined individually, BMI and WC were both negative predictors of mortality, but when BMI and WC were examined simultaneously, BMI was a negative predictor of mortality, whereas WC was a positive predictor of mortality. After controlling for WC, mortality risk decreased 21% for every standard deviation increase in BMI. After controlling for BMI, mortality risk increased 13% for every standard deviation increase in WC. The patterns of associations were consistent by sex, age, and disease status.",
            "output": [
                "Is body mass index inversely related to mortality in older people after adjustment for waist circumference?"
            ]
        },
        {
            "id": "task847-01c83f18a7ab4c2c96d37fb466a572c3",
            "input": "Advances in imaging technology have enhanced the detection of small nodular lesions during the course of chronic liver disease.', 'Between 1995 and 2002, the authors examined 154 consecutive patients with small hepatic nodules without hepatocellular carcinoma (HCC) over a median duration of 2.8 years. The median size of these nodules was 14 mm (range, 7-40 mm). The initial histopathologic diagnosis included high-grade dysplastic nodule (HGDN) (n=13), low-grade dysplastic nodule (LGDN) (n=42), and regenerative nodule (RN) (n=99).', 'A total of 29 (18.8%) nodules developed into HCC during the observation period. Cumulative HCC development rates at the first, third, and fifth year were 46.2%, 61.5%, and 80.8% for HGDN; 2.6%, 30.2%, and 36.6% for LGDN; and 3.3%, 9.7%, and 12.4% for RN, respectively. The rate of HCC development was significantly higher in the HGDN group than for other types (P<0.001). Multivariate analysis disclosed that histopathologic diagnosis (P<0.001) and findings on computed tomographic arterial portography (CT-AP) (P=0.004) were significantly associated with future HCC development. The hazard ratios of HGDN and LGDN were 16.8 (95% confidence interval [CI], 6.19-45.6) and 2.96 (95% CI, 1.20-7.31), respectively. A decrease in portal blood flow also showed a significantly high hazard ratio of 3.04 (95% CI, 1.42-6.50). Approximate annual development rate to HCC was 20% in patients with HGDN and 10% in LGDN.",
            "output": [
                "Do dysplastic nodules frequently develop into hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosis?"
            ]
        },
        {
            "id": "task847-fc46e98feb654ac2a919346137217de9",
            "input": "Characterizing young women's willingness to enter motherhood is critical to understanding the high rates of unintended pregnancy among women under 20 years. Our objectives were to discuss a measure called Positive Orientation towards Early Motherhood (POEM), and investigate its association with self-reported unintended pregnancy experience.\", 'We used data from 332 African-American women 13-19 years old recruited at public family planning and prenatal clinics in New Orleans. Using a series of ANOVAs and multinomial logistic regression, we assessed differences in POEM between four different outcome groups: women who were never pregnant and those who had only intended pregnancies, only unintended pregnancies and both unintended and intended pregnancies.', 'The data suggested that young women perceive pregnancy as an opportunity to assert responsibility, become closer with their families and achieve greater intimacy with their boyfriends. Multiple regression analysis indicated that this positive orientation toward early motherhood independently raised the likelihood that young women experienced unintended pregnancies. In particular, the perception that a pregnancy makes a young woman feel more responsible was associated with an increased likelihood that a young woman had only unintended pregnancies compared to no pregnancies at all. Interestingly, this perception did not differentiate young women who had only intended pregnancies from those who were never pregnant.",
            "output": [
                "Is a positive orientation toward early motherhood associated with unintended pregnancy among New Orleans youth?"
            ]
        },
        {
            "id": "task847-1adad8cbe57142aaa4a13039aed02b39",
            "input": "Observational studies suggest that dietary isoflavones reduce breast cancer risk, and this may be caused in part by effects on endogenous hormone concentrations. Because intestinal bacteria metabolize isoflavones, it was hypothesized that consumption of probiotic bacteria would enhance the biologic effects of isoflavones, including effects on endogenous hormones.', 'Twenty (20) postmenopausal breast cancer survivors and 20 healthy postmenopausal women completed four 42-day diet periods in a randomized, crossover design. They received one of the following: isolated soy protein; isolated milk protein; soy + probiotic capsules; or milk + probiotic capsules. Each protein supplement provided 0.38 g protein/(kg body weight/day) (26.6 +/- 4.5 g protein/day) and soy protein provided 0.64 mg isoflavones/(kg body weight/day) (44.4 +/- 7.5 mg isoflavones/day). Probiotic capsules provided 10(9) colony-forming units Lactobacillus acidophilus (strain DDS-1), Bifidobacterium longum, and 15-20 mg fructo-oligosaccharide.', 'Plasma samples were collected at baseline and after each diet for analysis of estrogens, follicle-stimulating hormone (FSH), androgens, and sex hormone?binding globulin (SHBG).', 'Hormone levels were not affected by soy, probiotic supplements, or equol producer status, and neither cancer status nor equol producer status altered the effects of soy or probiotics. Furthermore probiotics did not alter the effects of soy consumption. Soy protein tended to decrease SHBG compared to milk protein diets (p = 0.05), although both proteins significantly decreased SHBG relative to baseline (p = 0.0001 and p = 0.03).",
            "output": [
                "Does short-term soy and probiotic supplementation markedly affect concentrations of reproductive hormones in postmenopausal women with and without histories of breast cancer?"
            ]
        },
        {
            "id": "task847-b7df89b797b241518f6ca4592d29565f",
            "input": "Grape-seed (Vitis spp.) extract (GSE) is a widely used antioxidant dietary supplement. Chemotherapeutic agents such as cisplatin induce oxidative damage in the gastrointestinal tract and cause nausea and vomiting.', 'A rat model of simulated emesis was used to observe that cisplatin significantly increased kaolin consumption (or pica). Three GSEs from different sources were used in this study.', 'High-performance liquid chromatographic analysis of five major constituents (gallic acid, catechin, epicatechi, procyanidin B2, and epicatechin gallate) revealed that each constituent had different levels in the three GSEs. Extract #1, prepared in the laboratory of the investigators, had the lowest total polyphenol content (27.27 mg/g); Extract #2, obtained from a dietary supplement company in the United States, had a somewhat higher level (35.84 mg/g); and Extract #3, obtained from China, had the highest level (194.21 mg/g). Subsequently these GSEs were intraperitoneally administered in rats to evaluate their ability to decreasing cisplatin induced pica. At 10 mg/kg all three GSEs, with varying degrees of effect, decreased cisplatin-induced pica. The areas under the curves of kaolin intake from time 0 to 72 hours, compared to those in the cisplantin-only group, were reduced 45% for Extract #1 (p < 0.01), 54% for Extract #2 (p < 0.01), and 66% Extract #3 (p < 0.001).",
            "output": [
                "Do polyphenol contents in grape-seed extracts correlate with antipica effects in cisplatin-treated rats?"
            ]
        },
        {
            "id": "task847-9a5bb142b79c462898921095e0134cd2",
            "input": "There is an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). The aim of this study was to compare the prevalence of left sided adenomas in patients with IBD aged 55-64 years with a local age matched control population.', 'A review of clinical notes. The prevalence of adenomas in patients with IBD attending for either sigmoidoscopy or colonoscopy was compared with local age matched controls that participated in the national screening trial for colorectal cancer with flexible sigmoidoscopy.', \"Of 106 patients (61 male, 45 female, mean age of 59 years), 80 suffered from ulcerative colitis, 20 from Crohn's disease, and six from indeterminate colitis. All patients had undergone at least one flexible sigmoidoscopy and 75 had a colonoscopy. Distal adenomas were found in three patients with ulcerative colitis compared with 67 of 749 controls (2.8% v 8.9%, chi(2) = 4.6, p = 0.03).",
            "output": [
                "Are distal adenomatous polyps rare in patients with inflammatory bowel disease?"
            ]
        },
        {
            "id": "task847-3b590eb3009c49629ead562a074c2c24",
            "input": "High levels of wild-type alpha-synuclein are found in autopsied brain samples of idiopathic Parkinson's disease (PD), some familial PD, some Alzheimer's disease (AD) and Down's syndrome with dementia. Therefore, we have investigated whether overexpression of wild-type alpha-synuclein causes degeneration during adenosine, 3',5'-cyclic monophosphate (cAMP)-induced differentiation of murine neuroblastoma (NB) cells in culture. We have also studied whether selenomethionine can modify the effect of overexpression of alpha-synuclein during differentiation of NB cells.\", 'To study these issues, we established a murine neuroblastoma (NB) clone (NBP2-PN54-C20) that expressed high levels of wild-type human alpha-synuclein as determined by real time PCR and Western blot. We have utilized RO20-1724, an inhibitor of cyclic nucleotide phosphodiesterase, and prostaglandin A1 (PGA1), a stimulator of adenylate cyclase, or RO20-1724 and dibutyryl cAMP to induce terminal differentiation in over 95% of the cell population by elevating the intracellular levels of cAMP in NB cells. The viability of cells was determined by MTT assay and LDH leakage assay, and the degeneration was documented by photomicrographs.', 'The results showed that overexpression of human wild-type alpha-synuclein decreased viability and increased degenerative changes in comparison to those observed in vector control cells, when differentiation was induced by treatment with RO20-1724 and PGA1, but not with RO20-1724 and dibutyryl cAMP. When selenomethionine was added to NB cells overexpressing alpha-synuclein immediately after the addition of RO20-1724 and PGA1, the viability and degenerative changes were markedly reduced, suggesting the involvement of increased oxidative stress in the mechanism of action of alpha-synuclein. This protective effect was not observed after treatment with sodium selenite or methionine.",
            "output": [
                "Does selenomethionine prevent degeneration induced by overexpression of wild-type human alpha-synuclein during differentiation of neuroblastoma cells?"
            ]
        },
        {
            "id": "task847-7a25234c158a4df28e2afa20c4cf9cf7",
            "input": "Pituitary tumor-transforming gene (PTTG) is a multifunctional protein involved in several tumorigenic mechanisms, including angiogenesis. PTTG has been shown to promote angiogenesis, a key rate-limiting step in tumor progression, by up-regulation of fibroblast growth factor-2 and vascular endothelial growth factor.', 'To investigate whether PTTG regulates other angiogenic genes in thyroid cells, we performed angiogenesis-specific cDNA arrays after PTTG transfection. Two of the genes [inhibitor of DNA binding-3 (ID3) and thrombospondin-1 (TSP-1)] which showed differential expression in primary thyroid cells were validated in vitro and in vivo.', 'TSP-1 showed a 2.5-fold reduction and ID3 showed a 3.5-fold induction in expression in response to PTTG overexpression in vitro. Conversely, suppression of PTTG with small interfering RNA was associated with a 2-fold induction of TSP-1 and a 2.2-fold reduction in ID3 expression. When we examined TSP-1 and ID3 expression in 34 differentiated thyroid cancers, ID3 was significantly increased in tumors compared with normal thyroid tissue. Furthermore, ID3 expression was significantly higher in follicular thyroid tumors than in papillary tumors. Although mean TSP-1 expression was not altered in cancers compared with normal thyroids, we observed a significant independent association between TSP-1 expression and early tumor recurrence, with recurrent tumors demonstrating 4.2-fold lower TSP-1 expression than normal thyroid tissues.",
            "output": [
                "Does pituitary tumor-transforming gene regulate multiple downstream angiogenic genes in thyroid cancer?"
            ]
        },
        {
            "id": "task847-fa8acf6762fa4fc4b038b81930f3f5fa",
            "input": "The metabolic syndrome (MetS), characterized by central obesity, lipid and insulin dysregulation, and hypertension, is a precursor state for cardiovascular disease. The purpose of this analysis was to determine whether low serum sex hormone levels or clinical androgen deficiency (AD) predict the development of MetS.', 'Data were obtained from the Massachusetts Male Aging Study, a population-based prospective cohort of 1709 men observed at three time points (T1, 1987-1989; T2, 1995-1997; T3, 2002-2004). MetS was defined using a modification of the ATP III guidelines. Clinical AD was defined using a combination of testosterone levels and clinical signs and symptoms. The association between MetS and sex hormone levels or clinical AD was assessed using relative risks (RR), and 95% confidence intervals (95% CI) were estimated using Poisson regression models.', 'Analysis was conducted in 950 men without MetS at T1. Lower levels of total testosterone and SHBG were predictive of MetS, particularly among men with a body mass index (BMI) below 25 kg/m2 with adjusted RRs for a decrease in 1 sd of 1.41 (95% CI, 1.06-1.87) and 1.65 (95% CI, 1.12-2.42). Results were similar for the AD and MetS association, with RRs of 2.51 (95% CI, 1.12-5.65) among men with a BMI less than 25 compared with an RR of 1.22 (95% CI, 0.66-2.24) in men with a BMI of 25 or greater.",
            "output": [
                "Are low sex hormone-binding globulin , total testosterone , and symptomatic androgen deficiency associated with development of the metabolic syndrome in nonobese men?"
            ]
        },
        {
            "id": "task847-f055bdee546748ae8d92f9d94e5b74d8",
            "input": "The incidence of ureteral stenosis in kidney transplant recipients is 3%-8%. The treatment of ureteral stenosis has been traditionally operative reconstruction, although such intervention is associated with high rates of serious complications, including graft loss and even perioperative mortality. More recently, endourological treatment has been proposed due to its low morbidity.', 'The objective of this study was to assess the usefulness of balloon percutaneous dilatation as a treatment technique for ureteral stenosis in kidney transplant recipients.', 'Among 1000 kidney transplantations performed between 1980 and 2004, the coexistence of high creatinine values and urinary tract dilatation in the postoperative period, after discarding concomitant causes, was managed with a percutaneous nephrostomy. Once renal function recovered, antegrade pyelography was performed to confirm the presence and determine the location of ureteral stenosis. Ureteral dilatation was performed using a 5-French balloon-fitted angioplasty catheter.', 'Fifty-six patients were diagnosed with ureteral stenosis during follow-up, an incidence of 5.6%. Transluminal balloon dilatation was the first therapeutic option in 45 cases, whereas surgery was performed directly on 11 patients. Disappearance of the stenosis as well as maintenance of an improved creatinine level was verified in 45% of cases (20 patients). Two patients experienced graft loss. Both a short time to diagnosis after transplantation (P = .06) and the presence of a previous acute rejection episode (P < .05) were good prognosis factors for the endourologic solution of a ureteral stricture.",
            "output": [
                "Is endourological management better in early-onset ureteral stenosis in kidney transplantation?"
            ]
        },
        {
            "id": "task847-773033540d9d42588524826b3cb35b20",
            "input": "We investigated whether direct hemoperfusion with an immobilized polymyxin B column (DHP with PMX) could reduce the blood level of neutrophil elastase.', '20 sepsis patients were enrolled in the study. DHP with PMX was performed twice within a 24-hour period. Neutrophil elastase was measured 7 times.', 'Neutrophil elastase was 468 +/- 75.1 microg/l, while it was 1,531 +/- 201.7 microg/l immediately after the first session, declined to 351 +/- 73.9 microg/l before the second session of DHP with PMX, and increased again to 599.3 +/- 112.7 microg/l immediately after the second session, 328 +/- 73.7 microg/l at 24 h, 264 +/- 39.3 microg/l at 48 h, and 230 +/- 36.1 microg/l at 72 h after DHP with PMX. The levels from 48 h onwards were significantly lower compared with that before treatment.",
            "output": [
                "Does hemoperfusion with an immobilized polymyxin B column reduce the blood level of neutrophil elastase?"
            ]
        },
        {
            "id": "task847-cb474d70090846b99847a4f25d909552",
            "input": "To determine whether increased sequence variation occurs in regions of endogenous HIV-1 targeted by HIV-1-specific CD4 T cells. The presence of increased variation would be suggestive of immune evasion by HIV-1.', 'We performed a cross-sectional study of untreated HIV-1-infected subjects measuring HIV-1-specific interferon (IFN)-gamma-secreting CD4 T-cell responses against epitopes in Gag p17 and p24 and concurrent endogenous plasma HIV-1 RNA epitope sequence variation.', 'CD8- depleted IFNgamma enzyme-linked immunospot assays were used to identify regions of HIV-1 Gag recognized by CD4 T cells. Reverse transcriptase polymerase chain reaction and TA cloning were used to sequence endogenous plasma HIV-1 virus and identify variants.', 'CD4 T-cell epitopes in Gag p17 and p24 were identified in 5 individuals, and concurrent sequence information on endogenous HIV-1 was obtained in 4 of these individuals. Endogenous plasma HIV-1 RNA sequencing revealed no intrapatient amino acid sequence variation through identified epitopes.",
            "output": [
                "Do hIV-1-specific CD4+ T-cell responses are not associated with significant viral epitope variation in persons with persistent plasma viremia?"
            ]
        },
        {
            "id": "task847-8e71455dd4d14e1f8a7c6136d5599978",
            "input": "Chitosan has been shown to be a non-toxic and efficient vector for in vitro gene transfection and in vivo gene delivery through pulmonary and oral administrations. Recently, we have shown that chitosan/DNA nanoparticles could mediate high levels of gene expression following intrabiliary infusion 1. In this study, we have examined the possibility of using polyethylene glycol (PEG)-grafted chitosan/DNA complexes to deliver genes to the liver through bile duct and portal vein infusions.', 'PEG (Mw: 5 kDa) was grafted onto chitosan (Mw: 47 kDa, deacetylation degree: 94%) with grafting degrees of 3.6% and 9.6% (molar percentage of chitosan monosaccharide units grafted with PEG). The stability of chitosan-g-PEG/DNA complexes was studied by measuring the change in particle size and by agarose gel electrophoresis against bile or serum challenge. The influence of PEG grafting on gene transfection efficiency was evaluated in HepG2 cells using luciferase reporter gene. Chitosan and chitosan-g-PEG/DNA complexes were delivered to the liver through bile duct and portal vein infusions with a syringe pump. Gene expression in the liver and the distribution of gene expression in other organs were evaluated. The acute liver toxicity of chitosan and chitosan-g-PEG/DNA complexes was examined by measuring serum alanine aminotranferase (ALT) and aspartate aminotransferase (AST) activities as a function of time.', 'Both chitosan and chitosan-g-PEG displayed comparable gene transfection efficiency in HepG2 cells. After challenge with serum and bile, chitosan-g-PEG/DNA complexes, especially those prepared with chitosan-g-PEG (GD = 9.6%), did not form large aggregates like chitosan/DNA complexes but remained stable for up to 30 min. In addition, chitosan-g-PEG prevented the degradation of DNA in the presence of serum and bile. On day 3 after bile duct infusion, chitosan-g-PEG (GD = 9.6%)/DNA complexes mediated three times higher gene expression in the liver than chitosan/DNA complexes and yielded background levels of gene expression in other organs. On day 1 following portal vein infusion, gene expression level induced by chitosan/DNA complexes was hardly detectable but chitosan-g-PEG (GD = 9.6%) mediated significant transgene expression. Interestingly, transgene expression by chitosan-g-PEG/DNA complexes in other organs after portal vein infusion increased with increasing grafting degree of PEG. The ALT and AST assays indicated that grafting of PEG to chitosan reduced the acute liver toxicity towards the complexes.",
            "output": [
                "Do chitosan-g-PEG/DNA complexes deliver gene to the rat liver via intrabiliary and intraportal infusions?"
            ]
        },
        {
            "id": "task847-622eab6f22984e638925da9cc76609b2",
            "input": "Study the prevalence and correlates of ADHD symptoms in the National Health Interview Survey (NHIS).', 'NHIS includes 10,367 children ages 4 to 17. Parents report lifetime diagnosis of ADHD and complete the Strengths and Difficulties Questionnaire (SDQ). Prevalences of clinically significant ADHD and comorbid symptoms by race and ethnicity, gender, and age are presented.', 'Prevalence of clinically significant SDQ ADHD symptoms is 4.19% (males) and 1.77% (females). Male prevalence by race is 3.06% for Hispanics, 4.33% for Whites, and 5.65% for Blacks. Significant differences in prevalence occur across gender (p < .01) and among males across race (p < .01), age (p < .01), and income (p < .02). In the full sample, 6.80% of males and 2.50% of females have a parent-reported lifetime ADHD diagnosis but are negative for SDQ ADHD. Likewise, 1.59% of males and 0.81% of females are positive for SDQ ADHD but negative for parent report of ADHD diagnosis. SDQ ADHD positive children have substantially higher proportions of elevated scores on other SDQ subscales.",
            "output": [
                "Does prevalence and correlate of ADHD symptoms in the national health interview survey?"
            ]
        },
        {
            "id": "task847-b985fe94a68946c9860fcaa4629ddbf1",
            "input": "Nonoperative management of hemodynamically stable patients with blunt hepatic injuries has become the standard of care over the past decade. However, controversy regarding the role of in-hospital follow-up computed tomographic (CT) scans as a part of this nonoperative management scheme is ongoing. Although many institutions, including our own, have advocated routine in-hospital follow-up scans, others have suggested a more selective policy. Over time, we have perceived a low yield from follow-up studies. The hypothesis for this study is that routine follow-up imaging of asymptomatic patients is unnecessary.', 'All patients selected for nonoperative management of blunt hepatic injury were evaluated for utility of follow-up CT scans over a 4-year period.', 'There were 530 stable patients with hepatic injury on admission CT scans in which follow-up scans were obtained within a week of admission. All injuries were classified according to the revised American Association for the Surgery of Trauma Organ Injury Scale: 102 (19.2%) grade I, 181 (34.1%) grade II, 158 (29.8%) grade III, 74 (13.9%) grade IV, and 15 (2.8%) grade V. Follow-up scans showed that most injuries were either unchanged (51%) or improved (34.7%). Only three patients underwent intervention based on their follow-up scans: two patients had arteriography (one with therapeutic embolization) and one had percutaneous drainage. Each of those patients had clinical signs or symptoms that were indicative of ongoing hepatic abnormality.",
            "output": [
                "Is routine follow-up imaging unnecessary in the management of blunt hepatic injury?"
            ]
        },
        {
            "id": "task847-846e329fc89d42e29a932ea738313ee0",
            "input": "A prospective cohort study at our institution demonstrated a 48% mortality rate in warfarin anticoagulated trauma patients sustaining intracranial hemorrhage (ICH) compared with a 10% mortality rate in nonanticoagulated patients. Forty percent of patients demonstrated progression of their ICH, despite anticoagulation reversal, with a resultant 65% mortality rate. Seventy-one percent of these patients initially presented with a Glasgow Coma Scale (GCS) score > or = 14 and a 'minor' ICH. We postulated that early diagnosis of ICH and rapid anticoagulation reversal would reduce ICH progression rates and mortality.\", 'All anticoagulated patients with known or suspected head trauma were entered into the Coumadin protocol. The protocol ensured immediate triage and physician evaluation, head computed tomography (CT) scan, and fresh frozen plasma administration in patients with documented ICH.', 'Eighty-two patients were entered into the protocol with ICH documented in 19 (23%). Sixteen of 19 patients (84%) presented with GCS > or = 14. Median international normalized ratio (INR) for treated patients with ICH was 2.7 versus 2.5 for patients without ICH (p = 0.546). Mean time to initiate warfarin reversal was 1.9 hours for protocol patients versus 4.3 hours for preprotocol patients (p < 0.001). Two of 19 (10%) protocol patients with ICH died. However, both patients presented >10 hours after injury with a severe ICH. This 10% mortality rate is significantly less than the 48% mortality rate seen previously (p < 0.001) and is now consistent with that observed in similarly injured patients not on anticoagulation.",
            "output": [
                "Does rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduce hemorrhage progression and mortality?"
            ]
        },
        {
            "id": "task847-3acf9b1747514be7a389016d935bd3fc",
            "input": "Monocarboxylate (MC)-supplemented resuscitation has been shown to attenuate cellular injury after hemorrhagic shock. However, little is known about its effect on the central nervous system. The brain can use MCs such as lactate, pyruvate, and beta-hydroxybutyrate as energy substrates. The transit of MCs into the central nervous system is facilitated by the monocarboxylate transporters (MCTs), and their blockage can exacerbate neuronal damage. We examined the expression of MCT1 and markers specific for activation of astroglia and microglia in the brains of rats subjected to hemorrhagic shock and resuscitation. The hypothesis was that resuscitation with MC-based fluids would be accompanied by MCT1 up-regulation and glial response.', \"Rats (n = 30) were subjected to volume-controlled hemorrhage. Test groups included: sham, no resuscitation, resuscitation with normal saline, resuscitation with racemic lactated Ringer's solution, resuscitation with pyruvate Ringer's solution, and resuscitation with beta-hydroxybutyrate-containing ketone Ringer's solution. Plasma levels of MC were measured serially. The brains were investigated using GFAP, CD11b, CD43, MCT1, and GLUT1 immunohistochemistry.\", \"Rats resuscitated with MC-containing fluids had increased levels of MCT1 in brain endothelial cells and neuropil compared with sham rats. Enhanced staining was localized to the choroid plexus, astrocytic end feet, and white matter structures. None of the resuscitation treatment induced astrocytic hyperplasia, and pyruvate Ringer's solution and ketone Ringer's solution resuscitation led to hypertrophy of astrocytes.",
            "output": [
                "Does energy substrate-supplemented resuscitation affect brain monocarboxylate transporter levels and gliosis in a rat model of hemorrhagic shock?"
            ]
        },
        {
            "id": "task847-32bcfc29f1464228868720eb8fe2c5a0",
            "input": "To report 4 patients with Avellino corneal dystrophy (ACD) who were treated with 0.02% mitomycin C (MMC) during phototherapeutic keratectomy (PTK).', 'ACD was confirmed by polymorphism of the exon region in the BIGH3 gene using polymerase chain reaction followed by DNA sequencing analysis. Three patients with recurrent ACD and 1 patient with primary ACD underwent PTK. Intraoperative 0.02% MMC was applied topically with a soaked microsponge.', 'There was no recurrence of ACD in the heterozygotes, but there were recurrences with best-corrected visual acuity of 20/30 in the 2 homozygotes.",
            "output": [
                "Does mitomycin C inhibit recurrent Avellino dystrophy after phototherapeutic keratectomy?"
            ]
        },
        {
            "id": "task847-2c82aca1e3d047ca9c5adf84279d8570",
            "input": "Patients with chronic heart failure (CHF) have multiple abnormalities of autonomic regulation that have been associated to their high mortality rate. Heart rate recovery immediately after exercise is an index of parasympathetic activity, but its prognostic role in CHF patients has not been determined yet.', 'Ninety-two stable CHF patients (83M/9F, mean age: 51+/-12 years) performed an incremental symptom-limited cardiopulmonary exercise testing. Measurements included peak O2 uptake (VO2p), ventilatory response to exercise (VE/VCO2 slope), the first-degree slope of VO2 for the 1st minute of recovery (VO2/t-slope), heart rate recovery [(HRR1, bpm): HR difference from peak to 1 min after exercise] and chronotropic response to exercise [%chronotropic reserve (CR, %)=(peak HR-resting HR/220-age-resting HR)x100]. Left ventricular ejection fraction (LVEF, %) was also measured by radionuclide ventriculography.', 'Fatal events occurred in 24 patients (26%) during 21+/-6 months of follow-up. HRR1 was lower in non-survivors (11.4+/-6.4 vs. 20.4+/-8.1; p<0.001). All cause-mortality rate was 65% in patients with HRR1<or=12 bpm versus 11% in patients with HRR1>12 bpm (log-rank: 32.6; p<0.001). By multivariate survival analysis, HRR1 resulted as an independent predictor of mortality (chi2=19.2; odds ratio: 0.87; p<0.001) after adjustment for LVEF, VO2p, VE/VCO2 slope, CR and VO2/t-slope. In a subgroup of patients with intermediate exercise capacity (VO2p: 10-18, ml/kg/min), HRR1 was a strong predictor of mortality (chi2: 14.3; odds ratio: 0.8; p<0.001).",
            "output": [
                "Does early heart rate recovery after exercise predict mortality in patients with chronic heart failure?"
            ]
        },
        {
            "id": "task847-19d368ae32e249d888289c7e0b4c2e41",
            "input": "Measurement of pulse-wave velocity (PWV) is a non-invasive technique for assessing arterial stiffness. Although insulin resistance is associated with intimal-medial thickness of the carotid artery evaluated by B-mode ultrasonography, it is not known whether it is related to PWV. The aim of this study was to determine the relationship between homeostasis model assessment insulin sensitivity index (HOMA-%S) and PWV in non-diabetic subjects. We also examined the effects of oral glucose tolerance test (OGTT) 2-h glucose and plasma high-sensitivity C-reactive protein (CRP) on PWV, as these two parameters are associated with atherosclerosis.', 'A 75-g oral glucose tolerance test was performed in 1934 Japanese subjects who were undergoing health examinations. Of these subjects, we recruited 1541 non-diabetic subjects without chronic or acute inflammation, malignant diseases, autoimmune disorders, elevated serum creatinine levels, and abnormal hepatic function tests. Subjects who had an abnormal ankle/brachial blood pressure index of less than 0.9 were also excluded. Brachial-ankle PWV and plasma high-sensitivity CRP were measured on 1541 subjects who satisfied the admission criteria.', 'PWV was 12.55+/-1.61 (mean+/-sd) m/s and plasma CRP concentration was 0.4 mg/l (median, range, 0.1-5.8 mg/l) in the study subjects. By multivariate regression analysis, HOMA-%S was found to be an independent negative risk factor for PWV, while systolic blood pressure, age and triglycerides were positively associated with PWV. OGTT 2-h glucose was weakly and independently related to PWV in male subjects. Plasma CRP was not independently associated with PWV.",
            "output": [
                "Does insulin sensitivity independently influence brachial-ankle pulse-wave velocity in non-diabetic subjects?"
            ]
        },
        {
            "id": "task847-25a2104c6dfc4b649e78caf5057e299a",
            "input": "To investigate the association between adenoidectomy and/or tonsillectomy in childhood and asthma, allergic rhinitis (AR), and eczema in adolescence.', 'Longitudinal birth cohort study of 1328 members born in the city of Nijmegen. Information on ear-nose-throat surgery was documented at 2, 4, and 8 years of age. In 1055 cohort members the incidence of asthma, AR, and eczema at 21 years of age was determined using the International Study of Asthma and Allergic disease in Childhood Core Questionnaire. To analyse the association between adenoidectomy and/or tonsillectomy in childhood and asthma, AR, and eczema at age 21 years, relative risks (RR) were calculated.', 'Six hundred and ninety-three (66%) members completed the questionnaire at age 21 years, of whom 104 (15%) had undergone adenoidectomy and/or tonsillectomy and 262 (38%) reported atopic disease. Children who underwent adenoidectomy and/or tonsillectomy before the age of 8 years were not more likely to develop asthma, AR, or eczema at the age of 21 years than children who did not; RR 0.93 (95% confidence limits (CL) 0.52-1.64), RR 0.94 (CL 0.68-1.30), and RR 1.00 (CL 0.59-1.68), respectively.",
            "output": [
                "Is adenoidectomy and/or tonsillectomy in childhood associated with atopic disease later in life?"
            ]
        },
        {
            "id": "task847-7ef0405fe6914dc9b4f88c07aa59d873",
            "input": "Current serum testing for the detection of prostate cancer (PCa) lacks specificity. On diagnosis, the optimal therapeutic pathway is not clear and tools for adequate risk assessment of localized PCa progression are not available. This leads to a significant number of men having unnecessary diagnostic biopsies and surgery. A search for novel tumor markers identified macrophage inhibitory cytokine 1 (MIC-1) as a potentially useful marker. Follow-up studies revealed MIC-1 overexpression in local and metastatic PCa whereas peritumoral interstitial staining for MIC-1 identified lower-grade tumors destined for recurrence. Consequently, we sought to assess serum MIC-1 measurement as a diagnostic tool.', 'Using immunoassay determination of serum MIC-1 concentration in 1,000 men, 538 of whom had PCa, we defined the relationship of MIC-1 to disease variables. A diagnostic algorithm (MIC-PSA score) based on serum levels of MIC-1, total serum prostate-specific antigen, and percentage of free prostate-specific antigen was developed.', 'Serum MIC-1 was found to be an independent predictor of the presence of PCa and tumors with a Gleason sum > or =7. We validated the MIC-PSA score in a separate population and showed an improved specificity for diagnostic blood testing for PCa over percentage of free prostate-specific antigen, potentially reducing unnecessary biopsies by 27%.",
            "output": [
                "Does measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improve prostate cancer diagnosis?"
            ]
        },
        {
            "id": "task847-134181b4160a47da9f9805f7e6addd6b",
            "input": "To discover novel therapeutic targets for colon cancers, we previously surveyed expression patterns among 23,000 genes in colon cancer tissues using a cDNA microarray. Among the genes that were up-regulated in the tumors, we selected for this study peptidyl-prolyl isomerase-like 1 (PPIL1) encoding PPIL1, a cyclophilin-related protein.', 'Western blot analysis and immunohistochemical staining using PPIL1-specific antibody showed that PPIL1 protein was frequently overexpressed in colon cancer cells compared with noncancerous epithelial cells of the colon mucosa. Colony formation assay showed a growth-promoting effect of wild-type PPIL1 on NIH3T3 and HEK293 cells. Consistently, transfection of short-interfering RNA specific to PPIL1 into SNUC4 and SNUC5 cells effectively reduced expression of the gene and retarded growth of the colon cancer cells. We further identified two PPIL1-interacting proteins, SNW1/SKIP (SKI-binding protein) and stathmin. SNW1/SKIP is involved in the regulation of transcription and mRNA splicing, whereas stathmin is involved in stabilization of microtubules. Therefore, elevated expression of PPIL1 may play an important role in proliferation of cancer cells through the control of SNW1/SKIP and/or stathmin.",
            "output": [
                "Is overexpression of peptidyl-prolyl isomerase-like 1 associated with the growth of colon cancer cells?"
            ]
        },
        {
            "id": "task847-dff025a204b54cc6822c6dce1c832d69",
            "input": "Analyses of the pattern of p53 mutations have been essential for epidemiologic studies linking carcinogen exposure and cancer. We were concerned by the inclusion of dubious reports in the p53 databases that could lead to controversial analysis prejudicial to the scientific community.', 'We used the universal mutation database p53 database (21,717 mutations) combined with a new p53 mutant activity database (2,300 mutants) to perform functional analysis of 1,992 publications reporting p53 alterations. This analysis was done using a statistical approach similar to that of clinical meta-analyses.', 'This analysis reveals that some reports of infrequent mutations are associated with almost normal activities of p53 proteins. These particular mutations are frequently found in studies reporting multiple mutations in one tumor, silent mutations, or lacking mutation hotspots. These reports are often associated with particular methodologies, such as nested PCR, for which key controls are not satisfactory.",
            "output": [
                "Does meta-analysis of the p53 mutation database for mutant p53 biological activity reveal a methodologic bias in mutation detection?"
            ]
        },
        {
            "id": "task847-8d9180eef7e044ababdb4de0bcf7e1f0",
            "input": "Increased vascular endothelial growth factor (VEGF) expression is associated with colorectal cancer liver metastases. It is reasonable to expect that measurement of VEGF in liver metastases would provide the best prediction of therapy benefit for VEGF-targeted drugs, such as bevacizumab (Avastin). In this study, we evaluated how VEGF mRNA level in primary colorectal cancer was related to that in corresponding liver metastases. Thirty-one pairs of primary colorectal cancer and corresponding liver metastases were analyzed.', 'Formalin-fixed, paraffin-embedded tumor specimens were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse transcription. Quantitation of VEGF and internal reference gene (beta-actin) was done using real-time PCR (Taqman PCR).', 'There was no difference between median VEGF mRNA levels of primary colorectal cancer and liver metastases (median value 3.79 versus 3.97: P = 0.989). On an individual basis, there was a significant correlation in VEGF mRNA expression between primary colorectal cancer and corresponding liver metastases (r(s) = 0.6627, P < 0.0001). In addition, the VEGF mRNA levels of the patients who had two or more liver metastatic tumors were significantly higher than those of the patient who had solitary liver metastatic tumor in both primary cancer (5.02 versus 3.34: P = 0.0483) and liver metastases (4.38 versus 3.25: P = 0.0358).",
            "output": [
                "Is vascular endothelial growth factor messenger RNA expression level preserved in liver metastases compared with corresponding primary colorectal cancer?"
            ]
        },
        {
            "id": "task847-5f8aaca5408a46c88c5ebb239442fb2a",
            "input": "Since growth and de novo generation of cerebrovascular malformations were demonstrated, a strictly congenital model cannot be further supported as unique factor in the pathogenesis of cerebral arteriovenous malformations (AVMs). Vascular endothelial growth factor (VEGF) has previously been demonstrated to be highly expressed in AVMs by immunohistochemical methods. However, systemic VEGF levels have not been analysed previously. This study aimed to investigate VEGF plasma concentrations as a possible plasma marker for neovascularization in patients with cerebral AVMs compared to healthy controls.', 'The study included 17 patients with cerebral AVMs and 40 healthy controls. VEGF plasma concentrations were measured by a specific enzyme immuno-assay.', 'VEGF plasma concentrations were significantly higher in patients with cerebral AVMs (mean 140.9 pg/ml, SD 148.5 pg/ml and median 63.0 pg/ml) compared to a healthy control group (mean 44.7 pg/ml, SD 36.4 pg/ml and median 35.0 pg/ml), p = 0.0003.",
            "output": [
                "Are vascular endothelial growth factor plasma levels significantly elevated in patients with cerebral arteriovenous malformations?"
            ]
        },
        {
            "id": "task847-669e7c7123db448596e702e73f0cf3b6",
            "input": "In the past years the interaction of GH and 11beta hydroxysteroid dehydrogenase (11betaHSD) in the pathogenesis of central obesity has been suggested.', 'We studied the effects of 9 months of GH treatment on 11betaHSD activity and its relationship with body composition and insulin sensitivity in 30 men with abdominal obesity, aged 48-66 years, in a randomised, double-blind, placebo-controlled trial.', 'Urinary steroid profile was used to estimate 11betaHSD type 1 and 2 (11betaHSD1 and 11betaHSD2) activities. Abdominal s.c. and visceral adipose tissues were measured using computed tomography. Glucose disposal rate (GDR) obtained during a euglycaemic-hyperinsulinaemic glucose clamp was used to assess insulin sensitivity.', 'In the GH-treated group the 11betaHSD1 activity decreased transiently after 6 weeks (P < 0.01) whereas 11betaHSD2 increased after 9 months of treatment (P < 0.05). Between 6 weeks and 9 months, GDR increased and visceral fat mass decreased. Changes in 11betaHSD1 correlated with changes in visceral fat mass between baseline and 6 weeks. There were no significant correlations between 11betaHSD1 and 11betaHSD 2 and changes in GDR.",
            "output": [
                "Is gH effect on enzyme activity of 11betaHSD in abdominal obesity dependent on treatment duration?"
            ]
        },
        {
            "id": "task847-2bd2162d5b864edd89d380cd8dd20eda",
            "input": "The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed in patients with diabetes. In this study, we examined whether plasma OPG is associated with the glycaemic and vascular status of patients with type 1 diabetes.', 'Two gender-, age- and duration-comparable groups of type 1 diabetic patients either with (n = 199) or without (n = 192) signs of diabetic nephropathy were studied. Plasma OPG was determined by an ELISA.', 'The plasma OPG concentration was significantly higher in patients with nephropathy than those without (3.11 (2.49-3.99) vs 2.57 (2.19-3.21) (median (interquartiles), ng/ml), P < 0.001). Plasma OPG correlated with haemoglobin A1c (HbA1c), systolic blood pressure and age in both groups and, in addition, with kidney function in the nephropathic group. These correlations remained significant in multivariate models. In addition, we found that plasma OPG concentrations were increased among patients with cardiovascular diseases (CVD), both in the normoalbuminuric and the nephropathic groups. The differences between nephropathic and normoalbuminuric, as well as subgroups with and without CVD, could largely be ascribed to changes in HbA1c, age, systolic blood pressure and creatinine.",
            "output": [
                "Are plasma osteoprotegerin levels associated with glycaemic status , systolic blood pressure , kidney function and cardiovascular morbidity in type 1 diabetic patients?"
            ]
        },
        {
            "id": "task847-1886616137634d709b7f0127e653f7ba",
            "input": "We reported previously that the use of cephalosporin among premature neonates increased the risk of subsequent fungal sepsis. As a result, we recommended that ampicillin and gentamicin be used as empiric coverage for early-onset neonatal sepsis while culture results are awaited.', 'To describe antibiotic use during the first 3 days after birth for neonates admitted to the NICU and to evaluate the outcomes for neonates treated with 2 different antibiotic regimens.', 'We assembled a cohort of inborn neonates, from our deidentified administrative database, who had documented exposure to ampicillin during the first 3 days after birth. Infants treated concurrently with cefotaxime or gentamicin were evaluated, to identify the factors that were associated independently with death before discharge, with both univariate and multivariate analyses.', 'There were 128,914 neonates selected as the study cohort; 24,111 were treated concurrently with ampicillin and cefotaxime and 104,803 were treated concurrently with ampicillin and gentamicin. Logistic modeling showed that neonates treated with ampicillin/cefotaxime were more likely to die (adjusted odds ratio: 1.5; 95% confidence interval: 1.4-1.7) and were less likely to be discharged to home or foster care than were neonates treated with ampicillin/gentamicin. This observation was true across all estimated gestational ages. Other factors that were associated independently with death included immature gestational age, need for assisted ventilation on the day of admission to the NICU, indications of perinatal asphyxia or major congenital anomaly, and reported use of ampicillin/cefotaxime.",
            "output": [
                "Is empiric use of ampicillin and cefotaxime , compared with ampicillin and gentamicin , for neonates at risk for sepsis associated with an increased risk of neonatal death?"
            ]
        },
        {
            "id": "task847-800723832cea4032b823c52520efacf3",
            "input": "Adoptive cell transfer is described as an innovative and challenging option for the treatment of malignant melanoma. In the current study, the generation and expansion of telomerase-specific T-cells for adoptive cell transfer and their use in a syngeneic pancreatic carcinoma mouse model was investigated.', 'Telomerase-specific T-cells were generated either in vitro by coculture of human lymphocytes with telomerase-peptide-pulsed dendritic cells or in vivo by injection of peptide plus adjuvant into C57BL/6 mice. Spleens were harvested after immunization and lymphocytes were expanded in the presence of feeder cells. T-cells were tested in vitro against human leukocyte antigen (HLA)-matched, telomerase-positive pancreatic carcinoma cells. Tumor-bearing (subcutaneous) mice pretreated with cyclophosphamide were injected intravenously with the expanded cells.', 'It was possible to generate and expand telomerase-specific T-cells with cytotoxic activity. The protocol did not work as well in the murine setting. However, adoptive cell transfer with murine antigen-specific T-cells delayed disease progression in tumor-bearing mice significantly.",
            "output": [
                "Do telomerase-specific T-cells kill pancreatic tumor cells in vitro and in vivo?"
            ]
        },
        {
            "id": "task847-8c5c1d0b5697495184f31de9ff2f5765",
            "input": "The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age-related accumulation of advanced glycation end products (AGEs) could be one of these mechanisms. We undertook this study to investigate the role of the receptor for AGEs (RAGE) in mediating the cellular effects of AGEs on chondrocytes and fibroblast-like synoviocytes (FLS).', 'AGE levels in human cartilage were determined by fluorescence, browning, and pentosidine levels. Chondrocyte activation by AGEs was assessed as the release of proteoglycans and the synthesis of matrix metalloproteinase 1 (MMP-1) and type II collagen messenger RNA (mRNA). The activation of FLS by AGEs was measured by MMP-1 production and invasion through matrix proteins.', 'Patients with focal degeneration of cartilage showed increased AGE levels in their healthy cartilage compared with the levels in healthy cartilage from donors without cartilage degeneration (P < 0.01 for both fluorescence and browning; P not significant for pentosidine content). Stimulation of bovine chondrocytes with glycated albumin increased the release of proteoglycans by 110% (P < 0.001) and the production of MMP-1 mRNA by 200% (P = 0.028). In addition, OA FLS produced 240% more MMP-1 when stimulated with glycated albumin (P < 0.001). Glycated matrix or albumin increased the catabolic activity of OA FLS, which was assessed as invasive behavior, by 150% and 140% (P = 0.001 and P = 0.010), respectively. Effects of stimulation with AGEs were blocked by a neutralizing antibody against RAGE, but not by an isotype control.",
            "output": [
                "Does activation of receptor for advanced glycation end products in osteoarthritis lead to increased stimulation of chondrocytes and synoviocytes?"
            ]
        },
        {
            "id": "task847-c25ea2262d994a60b7257997b8ee3641",
            "input": "Patients with systemic lupus erythematosus (SLE) frequently suffer from infections, but the predisposing risk factors, as well as the exact frequency and nature of such infections, are not fully understood.', 'To describe the frequency, types and risk factors for infections in a group of Chinese patients in the early stage of SLE in Hong Kong.', 'Retrospective record study.', 'We reviewed the case records of 91 Chinese SLE patients, presenting <12 months after SLE diagnosis. Details of major infections (requiring intravenous antimicrobial therapy, or any confirmed mycobacterial infection) and minor infections were reviewed. Clinical and laboratory features, the systemic lupus erythematosus disease activity index (SLEDAI) at presentation and drug treatment were recorded and analysed.', 'There were 48 major infections and 62 minor infections during 260 patient-years of follow-up. A lymphocyte count < or =1.0 x 10(9)/l at presentation was independently associated with an increased risk for major infection: hazard ratio 4.7 (95%CI 1.6-13.7), p = 0.005. SLEDAI, use of corticosteroids and immunosuppressive therapy were all not associated with increased risk of infection.",
            "output": [
                "Is lymphopenia at presentation associated with increased risk of infections in patients with systemic lupus erythematosus?"
            ]
        },
        {
            "id": "task847-2a8e1fa9df7549e7b661ff52dae0918f",
            "input": "Approximately 50% of subjects with essential hypertension (EH) are insulin resistant, and this defect in insulin action could contribute to increased cardiovascular disease (CVD) risk in these patients. To test this hypothesis, we attempted to see if there was a link between insulin resistance (IR) and carotid intimal medial thickness (IMT), an early index of CVD, in patients with essential hypertension.', 'Ultrasound quantification of carotid IMT was performed in 79 hypertensive patients, and 63 patients (31 m and 32 f), defined as being free of plaque (IMT < 1.3 mm), were further subdivided into normal (<1.0 mm) and thickened (1-1.3 mm) IMT groups. Subjects in the thickened IMT group were older and had significantly (p < 0.05) higher plasma concentrations of fasting insulin, nitric oxide (NO(x)) and intercellular adhesion molecule 1 (ICAM-1). However, the two groups were not significantly different in terms of blood pressure, overall or regional obesity, fasting lipid levels, uric acid, concentrations of other cellular adhesion molecules or levels of C-reactive protein. There were significant (p < 0.05) correlations in the whole population between IMT and age, fasting insulin and NO(x), and multiple regression analysis identified fasting insulin as an independent predictor of IMT.",
            "output": [
                "Do insulin resistance/compensatory hyperinsulinemia predict carotid intimal medial thickness in patients with essential hypertension?"
            ]
        },
        {
            "id": "task847-b92eea90afad47f087f479ea73f6dffd",
            "input": "Sitosterolemia, a rare genetic disorder characterized by profoundly elevated plasma sitosterol concentrations, is associated with premature atherosclerosis in some individuals. This study was conducted to evaluate if the modest sitosterol elevations seen in the general population are also associated with the occurrence of coronary events.', 'A nested case-control study using stored samples from male participants in the Prospective Cardiovascular M\u00fcnster (PROCAM) study was performed. Each of 159 men who suffered a myocardial infarction or sudden coronary death (major coronary event) within 10 years of follow-up in PROCAM was matched with 2 controls (N = 318) by age, smoking status, and date of investigation. Analysis was performed using conditional logistic regression. Plasma sitosterol concentrations were elevated in cases compared with controls (4.94 +/- 3.44 micromol/L versus 4.27 +/- 2.38 micromol/L; P = 0.028). The upper quartile of sitosterol (>5.25 micromol/L) was associated with a 1.8-fold increase in risk (P < 0.05) compared with the lower three quartiles. Among men with an absolute coronary risk > or = 20% in 10 years as calculated using the PROCAM algorithm, high sitosterol concentrations were associated with an additional 3-fold increase in the incidence of coronary events (P = 0.032); a similar, significant relationship was observed between a high sitosterol/cholesterol ratio and coronary risk (P = 0.030).",
            "output": [
                "Are plasma sitosterol elevations associated with an increased incidence of coronary events in men : results of a nested case-control analysis of the Prospective Cardiovascular M\u00fcnster ( PROCAM ) study?"
            ]
        },
        {
            "id": "task847-cc353930d251483a9108726feb200f5f",
            "input": "Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans. We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin.', 'We studied the effects, in an obesity-promoting high-fat diet, of partial replacement of vegetable oils by EPA/DHA concentrate (6% EPA, 51% DHA) over a 5-week period in adult male C57BL/6J mice that either had free access to food or had their food intake restricted by 30%. At the end of the treatment, systemic markers of lipid and glucose metabolism and full-length adiponectin and leptin were measured. Adiponectin (Adipoq) and leptin (Lep) gene expression in dorsolumbar and epididymal white adipose tissue (WAT) and isolated adipocytes was quantified and adipokine production from WAT explants evaluated.', 'In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered. Food restriction decreased plasma triacylglycerols, glucose, insulin and leptin, but not adiponectin. EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat. Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA.",
            "output": [
                "Do polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet?"
            ]
        },
        {
            "id": "task847-808da5c36cb341c0a63c141bc0b650eb",
            "input": "Food supplements are known to affect the development of gastric adenocarcinoma. In this study, an animal model of gastric resection was used to investigate the effects of calcium carbonate on spontaneous development of gastric adenocarcinoma.', 'Ninety-two Wistar rats with gastric resections (performed to induce spontaneous gastric cancer) and 60 without resections (controls) were used to analyse the carcinogenic potential of different ion supplements in food.', 'Among the resected rats, cancer developed in 3 out of 18 (17%, NS) given NaCl but in 11 out of 18 (61%, p<0.01) exposed to calcium carbonate. No tumours were found in the unresected (unoperated) animals. These findings were further analysed by separately investigating the effects of calcium and carbonate ions on tumorigenesis in the gastric stump model. Cancer developed in one of 26 (4%) resected animals given a diet supplemented with CaHPO(4), which was lower than the rate observed in the resected control group fed a normal diet, although this difference was not statistically significant. However, tumour development increased significantly in the resected animals given a diet supplemented with NaHCO(3) (tumours in 13 out of 24 rats, 54%; p<0.01).",
            "output": [
                "Does dietary supplementation of carbonate promote spontaneous tumorigenesis in a rat gastric stump model?"
            ]
        },
        {
            "id": "task847-f5ca7dd5152f49eb80eabcacdc000bd3",
            "input": "To investigate the therapeutic potential of reverse gastric pacing (RGP) for obesity by studying the effects of RGP on food intake and symptoms in dogs.', 'The study was performed in 9 dogs in 3 sessions (control, strong RGP and moderate RGP). Gastric myoelectrical activity and food intake were measured in each session. RGP was performed using serosal electrodes implanted in the distal stomach at the physiological frequency of the intrinsic gastric myoelectrical activity with a pulse width of 550-950 ms. The amplitude of the stimulus was set at a level maximally tolerable by the animals in the strong RGP session and 50% of the maximum level in the moderate session.', '1) Compared with the control, strong RGP (p<0.001) and moderate RGP (p<0.01) significantly reduced the amount of food intake by 62.9% and 31.7%, respectively (p<0.05, ANOVA). 2) Whereas strong RGP induced significant symptoms, moderate RGP did not induce any significant symptoms in comparison with the control session. 3) The regularity and coupling of gastric myoelectrical activity were significantly impaired with both strong RGP and moderate RGP in the fasting state.",
            "output": [
                "Does reverse gastric pacing reduce food intake without inducing symptoms in dogs?"
            ]
        },
        {
            "id": "task847-da6b4fb43bc64f5abfcfcbb114070e61",
            "input": "Recent studies report negligible toxicity of oats in the majority of coeliac disease (CD) patients. It has previously been shown that children with untreated CD have circulating antibodies to oats avenin. In this study we performed serial assessments of anti-avenin antibodies in children under investigation for CD on a gluten-free diet with or without oats.', 'The study involved 116 children, randomized to a standard gluten-free diet or a gluten-free diet supplemented with oats. Sera were obtained from 86 children, 48 in the standard gluten-free group and 38 in the gluten-free oats group, of which 33 consumed at least 10 g of oats daily. IgA and IgG anti-avenin antibodies were monitored at 0, 3, 6 and 12 months. Nitric oxide metabolites were measured in 7 patients, with deviating antibody results.', 'There was a significant decrease in anti-avenin antibodies in both groups at the end as compared to the beginning of the study, (p<0.001), but no difference was found between the two groups. IgA titres already declined after 3 months. IgG titres, although significantly decreased, remained high in the majority of patients in both groups. Nitric oxide levels were high in four of the analysed samples.",
            "output": [
                "Do coeliac children on a gluten-free diet with or without oats display equal anti-avenin antibody titres?"
            ]
        },
        {
            "id": "task847-5f8bbbf08b794cf58ea6a840ac082a45",
            "input": "The purpose of this study was to test the hypothesis that maternal asthma symptoms and pulmonary function are related to adverse perinatal outcomes.', 'Asthmatic patients were recruited from the 16 centers of the Maternal Fetal Medicine Units. Forced expiratory volume in 1 second was obtained at enrollment and at monthly study visits, and the frequency of asthma symptoms was assessed from enrollment to delivery. Perinatal data were obtained at postpartum chart reviews.', 'The final cohort included 2123 participants with asthma. After adjustment for demographic characteristics, smoking, acute asthmatic episodes, and oral corticosteroid use, significant relationships were demonstrated between gestational hypertension and preterm birth and lower maternal gestational forced expiratory volume in 1 second. The data did not show any significant independent relationship between asthma symptom frequency and perinatal outcomes.",
            "output": [
                "Is spirometry related to perinatal outcomes in pregnant women with asthma?"
            ]
        },
        {
            "id": "task847-8de0f06e058647ffba079cb7ef343aa2",
            "input": "To ascertain body temperatures in older people.', 'Analysis of oral temperatures obtained from elderly subjects residing in the community and nursing home.', 'A single nursing home, office setting, and community center.', 'One hundred nursing home residents and 50 subjects residing in the community.', 'Three oral temperatures were measured in nursing home residents and once in community dwellers using an electronic digital thermometer.', 'The average age of subjects was 80.7. Temperatures ranged from 94.0 degrees F to 99.6 degrees F. In nursing home subjects, the 6 a.m. mean temperature was 97.3 degrees F, 4 p.m. mean was 97.4 degrees F, and 10 p.m. mean was 97.8 degrees F. The single midday mean temperature in community dwellers was 97.7 degrees F. Ninety-seven of 100 (97%), 94 of 100 (94%), and 83 of 96 (86%) recordings were below 98.6 degrees F in nursing home residents at 6 a.m., 4 p.m., and 10 p.m., respectively. Similarly, 45 of 50 (90%) community dwellers had midday temperatures below 98.6 degrees F. Repeated-measures analysis demonstrated an increase in temperature during the day. The increase was greatest in the youngest old, with no significant change in body temperature over the course of the day in the oldest old.",
            "output": [
                "Is older colder : temperature range and variation in older people?"
            ]
        },
        {
            "id": "task847-391cb16caf744fde96df6c9cdde94413",
            "input": "Chronic urticaria is one of the perplexing problems faced by clinicians. There are a few reports associating house dust mite sensitivity with chronic urticaria, based upon the patient's history as well as intradermal skin testing and in vitro analysis.\", 'To investigate the possible association between house dust mite sensitivity and chronic urticaria.', 'In this case control study three groups of patients were enrolled. Group I: Chronic urticaria (73 subjects). Group II: Chronic urticaria with collateral allergic disorders (49 subjects). Group III: Normal subjects without chronic urticaria or other allergies (25 subjects). All the patients underwent skin prick testing with antigens of the house dust mite, Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF), with positive and negative controls.', 'Among the patients with chronic urticaria, 78/122 (64%) patients had skin sensitivity to house dust mites. Out of these, 39/73 (53%) had chronic urticaria alone and 39/49 (79%) had chronic urticaria with other associated allergies. Among the normal control subjects, 7/25(28%) reacted positively to house dust mites.",
            "output": [
                "Is house dust mite sensitivity a factor in chronic urticaria?"
            ]
        },
        {
            "id": "task847-8a25e69783904c72ae3263d6293857f9",
            "input": "Several collagenolytic matrix metalloproteinases (MMPs) have recently been identified in gingival fibroblasts, while secreted cysteine proteinases could also participate in connective tissue destruction in periodontitis. To clarify their involvement, we examined enzyme release during collagen breakdown by cultured cytokine-stimulated fibroblasts.', 'Gingival fibroblasts were derived from four chronic periodontitis patients and cultured on collagen gels in serum-free medium for 1-4 days. Collagenolysis was measured by hydroxyproline release into the medium. Proteinases were assessed by electrophoresis and immunoblotting.', 'Adding interleukin-1beta resulted in progressive gel breakdown. This was associated particularly with a shift in MMP-1 band position from proenzyme to active enzyme and the appearance of active as well as proenzyme forms of cathepsin B. There was also partial processing of pro-MMP-13 and increased immunoreactivity for active cathepsin L. In addition, both pro-forms and active forms of MMP-8, membrane-type-1-MMP and MMP-2 were present in control and treated cultures.",
            "output": [
                "Is collagen degradation by interleukin-1beta-stimulated gingival fibroblasts accompanied by release and activation of multiple matrix metalloproteinases and cysteine proteinases?"
            ]
        },
        {
            "id": "task847-518369b921c04eef9b60233cd00a2469",
            "input": "Matrix metalloproteinases (MMPs) play pivotal roles in tumor progression. MMP-13 (collagenase-3) digests collagen and other extracellular components.', 'Reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and zymograph were used to study the roles of MMP-13 during the neoplastic process of oral squamous cell carcinoma (OSCC).', 'Increase of MMP-13 mRNA and protein expression in OSCC cell lines relative to cultivated normal oral keratinocytes was found. MMP-13 mRNA expression in OSCC was significantly higher than in non-cancerous match tissue (NCMT) in 36 tissue pairs. Esophageal squamous cell carcinoma also exhibited high MMP-13 mRNA expression. The percentage of OSCC exhibiting strong MMP-13 immunoreactivity was significantly higher than pre-invasive lesion and NCMT. Treatment with >5 microm epigallocatechin-3-gallate (EGCG) to OEC-M1 cells suppressed the expression and activity of MMP-13.",
            "output": [
                "Do increase of MMP-13 expression in multi-stage oral carcinogenesis and epigallocatechin-3-gallate suppress MMP-13 expression?"
            ]
        },
        {
            "id": "task847-8fe19f89a9a34b29a9af4896d54938f5",
            "input": "The purpose of this study was to determine the feasibility and effectiveness of implementing a validated suturing curriculum as a free-standing continuing medical education (CME) course.', 'Eighteen participants (9 practicing surgeons, 9 surgery residents) attended a 4-hour laparoscopic suturing CME course. After viewing an instructional videotape all participants had their baseline performance measured on a fundamentals of laparoscopic surgery-type videotrainer suture model. Participants then practiced on the model with active instruction from 6 proctors until a previously reported proficiency level was achieved or until the course ended. Performance was scored objectively based on time and errors. Precourse and postcourse questionnaires were collected.', 'Participants trained for 2.6 +/- .8 hours and performed 37 +/- 11 repetitions. Although no participant was proficient at baseline, 72% achieved the proficiency level by the end of the course. Participants showed 44% improvement in objective scores and 34% improvement according to subjective self-rating.",
            "output": [
                "Does intensive continuing medical education course training on simulators result in proficiency for laparoscopic suturing?"
            ]
        },
        {
            "id": "task847-2c587c0d4f2f4cfea1b0e7c12f89ee04",
            "input": "The reporting of standardized uptake value (SUV) on fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET) in colorectal cancer is becoming common practice, but its clinical utility remains to be determined. This study was designed to compare FDG-PET uptake as measured by SUV with operative findings.', 'A colorectal cancer database was queried to identify patients who underwent FDG-PET scans with reported SUVs followed by exploratory laparotomy within 3 months and compare these results to determine FDG-PET sensitivity.', 'Of 46 patients, 16 (34.8%) were found to be have increased extent of disease intraoperatively than seen on FDG-PET scan. This patient population had a statistically significant decreased mean maximal SUV than the patients whose FDG-PET scan equaled intraoperative findings (P < .025).",
            "output": [
                "Do abdominal positron-emission tomography lesions with increased standardized uptake values correlate with intraoperative findings?"
            ]
        },
        {
            "id": "task847-b2f286e79bbf4c6a83521c6ca2026a06",
            "input": "The study was conducted to evaluate the vascular effects of chlorthalidone, a distal tubule-acting natriuretic agent, in hypertensive patients with nondiabetic metabolic syndrome, an insulin-resistant condition characterized by endothelial dysfunction and high risk for diabetes mellitus development.', 'Thirteen untreated hypertensive patients with Adult Treatment Panel-III-defined nondiabetic metabolic syndrome were assigned to 3-month treatment with chlorthalidone. The end-points were baseline and post-treatment evaluation of (1) forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine infusion to test endothelial-mediated vasomotor function, with sodium nitroprusside as a control for endothelium-independent vasodilatation; (2) minimum forearm vascular resistance, the ratio of mean blood pressure and maximal blood flow in response to 13-minute arterial occlusion, as a hemodynamic correlate of arteriolar structure; and (3) transcapillary albumin escape rate (the 1-hour decay rate of (125)I-albumin, 6-8 microC ev) as a measure of systemic capillary permeability. Additional measurements included baseline and posttreatment lipids, fasting, and postload glucose and insulin as well as the homeostasis model assessment, an index of insulin sensitivity.', 'Chlorthalidone reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum forearm resistance, and slowed the transcapillary albumin escape rate. Metabolic parameters did not change significantly except for an increase in low-density lipoprotein cholesterol levels.",
            "output": [
                "Does chlorthalidone improve endothelial-mediated vascular responses in hypertension complicated by nondiabetic metabolic syndrome?"
            ]
        },
        {
            "id": "task847-a34aa4297319495bbef8693a9837d470",
            "input": "Heparin is used in the treatment of venous and arterial thromboembolic events, including unstable angina. Once unfractionated heparin is discontinued during the acute phase of unstable angina, it has been demonstrated that the disease process may be reactivated within hours. It is hypothesized that this reactivation may be a result of direct platelet activation by heparin that can linger even after the drug itself has been stopped. Prior studies have shown that heparin can either increase or decrease platelet activation. More recent studies have also shown conflicting effects of unfractionated heparin on PFA-100 testing.', 'We studied the in-vitro effects of unfractionated heparin on platelet function and PFA-100 testing. Unfractionated heparin was incubated with whole blood taken from 18 healthy volunteers. Platelet activation and aggregation was assessed with and without the presence of heparin.', 'Platelet aggregation and activation were increased in the presence of heparin. Unfractionated heparin also significantly prolonged collagen/adenosine diphosphate closure time but did not affect collagen/epinephrine closure time.",
            "output": [
                "Does heparin therapy lead to platelet activation and prolongation of PFA-100 closure time?"
            ]
        },
        {
            "id": "task847-ba86f4aeca7447d7b1dad2e3455d1f50",
            "input": "To examine whether connective tissue growth factor(CTGF) induces the production of fractalkine(FLK) by glomerular mesangial cells of rats, and explore the mechanism of signal pathway of CTGF actions.', 'The mRNA expression of FLK was analyzed by RT-PCR in cultured mesangial cells stimulated by CTGF. The protein of FLK in the supernatants of cells was determined by ELISA. The chemotactic effect of the supernatants on monocytes was assessed by the in vitro chemotaxis assay. The phosphorylation of p42/44 MAPK was assessed by Western blot.', 'Treatment of the cells with CTGF enhanced the mRNA expression of FLK and concentration of FLK in the supernatants. Pretreatment of the supernatants of CTGF-treated cells with anti-FLK antibodies partially inhibited the chemotactic effect of the supernatants on monocytes. CTGF increased the p42/44MAPK phosphorylation. Pretreatment of the cells with PD98059 or UO126, inhibitors of phosphorylated p42/44 MAKP, decreased the CTGF-induced expression of phosphorylated p42/44 MAPK and concentration of FLK in supernatants.",
            "output": [
                "Does [ p42/44 MAPK mediate synthesis of fractalkine by mesangial cells stimulated by connective tissue growth factor ]?"
            ]
        },
        {
            "id": "task847-2cdeb23012144eaa8b161a0af675b63e",
            "input": "A fundamental prerequisite for using degradable synthetic biopolymers as composite skin substitutes is the ability to establish vascular tissue. PEGT/PBT block-copolymer matrices have previously been shown as a favorable dermal substitute. In this study, quantitative data on neovascularization of PEGT/PBT block-copolymer matrices are presented.', 'PEGT/PBT-block-copolymer discs of three different pore diameters (1: < 75 microm, 2: 75-212 microm, 3: 250-300 microm) were implanted into dorsal skinfold chambers of balb/c mice. Histological sections were evaluated 7, 14, and 21 days post implantation by light and scanning electron microscopy. Blood vessel analysis was performed by means of digital image analysis (n = 288) of hematoxylin/eosin stained sections within apical (AOF) and basal (BOF) observation fields of the matrices.', 'Twenty-one days after implantation the density of blood vessels within the BOF of the scaffolds with a pore size of 75-212 and 250-300 microm were 4.6 +/- 0.45 and 5.8 +/- 0.62 (mean +/- S.E.M.; blood vessel profiles (BVF)), respectively. In <75 microm scaffolds, smaller numbers of BVF were found (4.2 +/- 0.39). In contrast, the evaluation within the AOF revealed significantly higher numbers of BVF in 75-212 microm group (3.5 +/- 0.49) and 250-300 microm group (4.5 +/- 0.66) as compared to the < 75 microm group (2.3 +/- 0.48).",
            "output": [
                "Does analysis of neovascularization of PEGT/PBT-copolymer dermis substitute in balb/c-mice?"
            ]
        },
        {
            "id": "task847-e5762a86b8e548ae890a558037343802",
            "input": "Human adipose tissue produces several adipokines, including the newly identified protein cathepsin S (CTSS), a cysteine protease involved in the pathogenesis of atherosclerosis. Obesity is characterized by high levels of CTSS in the circulation and in sc white adipose tissue (scWAT).', 'We investigated the effect of surgery-induced weight loss on circulating CTSS and its protein expression in scWAT.', 'Fifty morbidly obese women before and 3 months after surgery and 10 healthy lean women were studied. We analyzed the relationships between circulating CTSS and clinical and biological parameters. Immunohistochemistry of the CTSS protein variations in scWAT was performed.', 'Weight loss decreased by 42% (P < 0.0001) the circulating CTSS levels, which correlated with changes in body weight (P = 0.03). We observed a significant decrease in CTSS enzymatic activity by 25% after weight loss (P = 0.001). Adipose tissue CTSS content was reduced by 30% (P = 0.002) after surgery. The variations in CTSS expression in scWAT after surgery correlated with changes in circulating CTSS serum levels (P = 0.03). Most of the correlations between CTSS and clinical and biological parameters disappeared after adjustment for body mass index, emphasizing the strong link between CTSS and corpulence in humans.",
            "output": [
                "Does weight loss reduce adipose tissue cathepsin S and its circulating levels in morbidly obese women?"
            ]
        },
        {
            "id": "task847-3dda5919249043ec98522dda34aaf36a",
            "input": "GH acts through the GH receptor (GHR), whose polymorphisms might affect the growth response to recombinant human GH (rhGH).', 'The objective of this study was to investigate possible influences of GHR polymorphisms on the growth response to rhGH in GH-deficient (GHD) children.', 'This was a 2-yr study (first year, spontaneous growth; second year, growth during rhGH treatment).', 'This study was performed at a referral center.', 'Fifty-four prepubertal GHD children (11 females; mean age, 7.8 yr; sd, 3.96) were studied.', 'Patients were treated with rhGH (0.2 mg/kg.wk) for at least 1 yr after diagnosis. Growth velocity (GV) was measured 1 yr before treatment and during the first treatment year. GHR exons were amplified by PCR using pairs of intronic primers. The presence of single or multiple mismatches in the PCR products was revealed by denaturing high-pressure liquid chromatography. For exons in which mismatches were found by denaturing high-pressure liquid chromatography, direct sequencing was performed by automatic sequencer.', 'Before the start of treatment, the mean height (Ht) sd score was -1.93 (sd, 0.70), and the mean GV sd score was -1.49 (sd, 1.26).', 'The posttreatment (first 12 months) mean GV sd score was 3.55 (sd, 3.27). Molecular analysis revealed a high frequency of GHR polymorphisms; in particular: exon 3 deletion (Del 3) in 26 subjects (48%), polymorphism 504 A>G at codon 168 of exon 6 in 44 (82%), and polymorphism 1576 A>C at codon 526 of exon 10 in 35 (65%). In most patients, these different polymorphisms recurred in association. We found no significant differences in GV between the groups of subjects defined by the polymorphic genotypes.",
            "output": [
                "Do common polymorphisms of the growth hormone ( GH ) receptor correlate with the growth response to exogenous recombinant human GH in GH-deficient children?"
            ]
        },
        {
            "id": "task847-274d49c5832d49c89a1d46c2c125cd25",
            "input": "To determine whether full-scale simulation (SIM) is superior to interactive problem-based learning (PBL) for teaching medical students acute care assessment and management skills.', 'Randomized controlled trial.', 'Simulation center at a U.S. medical school.', 'Thirty-one fourth-year medical students in a week-long acute care course.', 'After institutional review board approval and informed consent, eligible students were randomized to either the SIM or PBL group. On day 1, all subjects underwent a simulator-based initial assessment designed to evaluate their critical care skills. Two blinded investigators assessed each student using a standardized checklist. Subsequently, the PBL group learned about dyspnea in a standard PBL format. The SIM group learned about dyspnea using the simulator. To equalize simulator education time, the PBL group learned about acute abdominal pain on the simulator, whereas the SIM group used the PBL format. On day 5, each student was tested on a unique dyspnea scenario.', \"Mean initial assessment and final assessment checklist scores and their change for the SIM and PBL groups were compared using the Student's t-test. A p < .05 was considered significant. The SIM and PBL groups had similar mean (PBL 0.44, SIM 0.47, p = .64) initial assessment scores (earned score divided by maximum score) and were deemed equivalent. The SIM group performed better than the PBL group on the final assessment (mean, PBL 0.53, SIM 0.72, p < .0001). When each student's change in score (percent correct on final assessment minus percent correct on the initial assessment) was compared, SIM group students performed better (mean improvement, SIM 25 percentage points vs. PBL 8 percentage points, p < .04)",
            "output": [
                "Is simulation-based training superior to problem-based learning for the acquisition of critical assessment and management skills?"
            ]
        },
        {
            "id": "task847-fc58fed7237c4467b586649d8cdbce7b",
            "input": "The role of CXCR4 in bone marrow localization of neuroblastoma cells has been recently proposed. The aim of this study was to investigate the expression and chemotactic functionality of CXCR4 in human metastatic neuroblastoma cells isolated from the bone marrow and, for comparison, in a panel of neuroblastoma cell lines.', 'CXCR4 expression and chemotactic functionality were investigated in metastatic neuroblastoma cells isolated from patient bone marrow and in neuroblastoma cell lines. The former cells were isolated as CD45- or GD2+ cells by immunomagnetic bead manipulation. Chemotactic assays were done in a transwell system. Regulator of G protein signaling expression was investigated by reverse transcription-PCR.', 'Metastatic neuroblastoma cells consistently expressed CXCR4, which was also detected in 5 of 10 neuroblastoma cell lines. CXCL12 did not stimulate the chemotaxis of primary tumor cells or cell lines in either normoxia or hypoxia, irrespective of CXCR4 up-regulation detected under the latter condition. Accordingly, neuroblastoma cells failed to modulate filamentous actin and to activate mitogen-activated protein kinase upon treatment with CXCL12. RGS16 mRNA was consistently expressed in primary tumor cells and cell lines, but its down-regulation by RNA interference did not restore CXCR4 chemotactic functionality.",
            "output": [
                "Does cXCL12 attract CXCR4+ human metastatic neuroblastoma cells : clinical implications?"
            ]
        },
        {
            "id": "task847-65db35f5152d4f1ba33c9e5aed7a568e",
            "input": "Chronic idiopathic urticaria is a common skin disorder characterized by recurrent, transitory, itchy weals for more than 6 weeks. An autoimmune origin has been suggested based on the findings of auto-antibodies (Abs) directed against either the alpha subunit of the high-affinity IgE receptor or the IgE molecule in nearly half of the patients.', 'To identify other autoantigen targets in patients with chronic idiopathic urticaria.', \"We used pooled IgG derived from 133 patients with chronic idiopathic urticaria to screen a random peptide library to identify disease-relevant autoantigen peptides. Among the identified peptides, one was recognized by the vast majority of patients' sera. Abs against this peptide were affinity purified from the patients' sera and assayed for their ability to induce histamine release from basophils.\", \"We identified a peptide that showed similarity with the low-affinity IgE receptor (Fc epsilonRII/CD23) expressed on lymphomonocytes and eosinophils. Anti-peptide IgG Abs purified from the patients' sera bound cell surface CD23 and were able to induce histamine release from basophils. This effect appeared to be mediated by the release of major basic protein from eosinophils upon engagement of CD23. The same effects were obtained with the sera from mice immunized with the CD23 peptide.",
            "output": [
                "Do in chronic idiopathic urticaria autoantibodies against Fc epsilonRII/CD23 induce histamine release via eosinophil activation?"
            ]
        },
        {
            "id": "task847-1f675edffb464343bae637adc07d2fe1",
            "input": "We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate-to-severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits.', 'Peripheral blood mononuclear cells (PBMC) were isolated from children (n = 53) at baseline and at the end of an 8-week supplementation period during which they received a probiotic (Lactobacillus fermentum PCCtrade mark) (n = 26) or a placebo (n = 27). A further sample was collected at 16 weeks (8 weeks after ceasing the supplement). Cytokine (IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNF-alpha) responses to allergens (egg ovalbumin (OVA), beta lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT)), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus (HKLB)), heat-killed Staphylococcus aureus (HKSA), Staphylococcus aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared.', 'The administration of probiotics was associated with a significant increase in T-helper type 1(Th1-type) cytokine IFN-gamma responses to PHA and SEB at the end of the supplementation period (week 8: P = 0.004 and 0.046) as well as 8 weeks after ceasing supplementation (week 16: P = 0.005 and 0.021) relative to baseline levels of response. No significant changes were seen in the placebo group. The increase in IFN-gamma responses to SEB was directly proportional to the decrease in the severity of AD (r = -0.445, P = 0.026) over the intervention period. At the end of the supplementation period (week 8) children receiving probiotics showed significantly higher TNF-alpha responses to HKLB (P = 0.018) and HKSA (P = 0.011) but this was no longer evident when supplementation ceased (week 16). Although IL-13 responses to OVA were significantly reduced in children receiving probiotics after 8 weeks (P = 0.008), there were no other effects on allergen-specific responses, and this effect was not sustained after ceasing supplementation (week 16). There were no effects on vaccine-specific responses, or on responses to any of the stimuli assessed.",
            "output": [
                "Are clinical effects of probiotics associated with increased interferon-gamma responses in very young children with atopic dermatitis?"
            ]
        },
        {
            "id": "task847-ab5942b4ec7145359e5060dafd9a0d89",
            "input": "Tumor necrosis factor-alpha (TNF-alpha) is a major pro-inflammatory cytokine. Recently, the G-308A polymorphism of the TNF-alpha gene has been associated with modified gene expression and increased TNF-alpha production in the -308A allele. We evaluated its influence on the incidence and clinical course of membranous glomerulonephritis.', 'We studied 53 patients with biopsy-proven primary membranous glomerulonephritis followed up for 5.7 +/- 4.9 years. 100 volunteers were analyzed as controls. According to the slope of the curve of reciprocal serum creatinine against time, group A (slow progressors, n = 35) and group B (fast progressors, n = 18) were defined. TNF-alpha G-308A polymorphism was determined by polymerase chain reaction amplification.', 'The frequency of the A-allele (associated with higher TNF-alpha levels) was significantly higher in patients than control subjects (patients: G-allele: 0.66, A-allele: 0.34; controls: G-allele 0.85, A-allele 0.15, p < 0.001). Similarly, the genotype distribution differed significantly between our study and control populations (patients: GG-genotype: 41.5%, GA: 49.1%, AA 9.4%; controls: GG: 71%, GA: 27%, AA 2%, p = 0.001). Age, renal function, proteinuria and blood pressure were similar at the time of renal biopsy between patients with different genotypes (NS). There was also a tendency towards an overpresentation of the A-allele in group B indicating a possible impact on the progression of membranous nephropathy, but a significance was not reached. Furthermore, no impact on renal survival in the Kaplan- Meier analysis was detected (NS).",
            "output": [
                "Is tumor necrosis factor-alpha gene G-308A polymorphism a risk factor for the development of membranous glomerulonephritis?"
            ]
        },
        {
            "id": "task847-ded931cf04b74038aa9376a3ee46d538",
            "input": "Dietary methionine affects cholesterol metabolism in growing rats. Methionine effects on adult rats and mechanisms by which methionine alters the lipid metabolism are not fully elucidated. We investigated possible mechanisms by which dietary methionine acts on lipid metabolism of adult rats.', 'Male adult rats were divided into three groups (n=10) and were fed casein-based diets differing in methionine concentration (low-methionine diet: 0.96 g/kg; adequate-methionine diet: 2.22 g/kg, high-methionine diet: 6.82 g/kg) for 4 weeks. Concentrations of triacylglycerols and cholesterol in plasma and lipoproteins, concentration of homocysteine in plasma, concentration of cholesterol in liver, fecal lipid excretion, expression of hepatic HMG-CoA reductase, phosphatidylethanolamine N-methyltransferase 2 (PEMT-2) and of LDL receptor were measured.', 'Rats fed the high-methionine diet had higher plasma homocysteine concentrations than rats fed the low-methionine diet (p<0.05). Although concentrations of cholesterol in plasma and lipoproteins were not different between the groups, there was a distinct positive correlation between circulating plasma homocysteine and plasma cholesterol (R(2)=0.55, p<0.001). The fecal excretion of cholesterol and bile acids was not altered by dietary methionine. The relative mRNA concentration of HMG-CoA reductase and of LDL receptor remained unaffected by dietary methionine. Gene expression of PEMT-2 was higher in rats fed the high-methionine diet than in rats fed the other diets (p<0.05).",
            "output": [
                "Is methionine-induced elevation of plasma homocysteine concentration associated with an increase of plasma cholesterol in adult rats?"
            ]
        },
        {
            "id": "task847-85e836b01cd4450ba53752e9e548c624",
            "input": "During therapy consisting of 6MP and MTX, metabolites accumulate in the erythrocytes. The erythrocyte levels of metabolites reflect the intensity of therapy. Whether they are associated with hepatotoxicity manifested as histological liver changes is not known. We studied the association of the metabolites and cumulative doses of 6MP and MTX with histological liver disease.', 'Serial measurements of E-TGN, E-MTX, and ALT during maintenance therapy were performed and cumulative doses of 6MP and MTX were calculated as g/m2 in 16 children with ALL. Each subject underwent a percutaneous liver biopsy at the end of therapy to screen for histological liver disease.', 'No differences in E-TGN, E-MTX, or cumulative doses of 6MP or MTX were detected in the children with ALL with liver fibrosis compared to those without fibrosis, or in the children with less liver fatty change compared to those with more fatty change. Serum median ALT levels correlated significantly positively with cumulative doses of 6MP during therapy (rS = 0.527, P = 0.036), but not with cumulative doses of MTX, or E-TGN, or E-MTX.",
            "output": [
                "Do erythrocyte concentrations of metabolites or cumulative doses of 6-mercaptopurine and methotrexate predict liver changes in children treated for acute lymphoblastic leukemia?"
            ]
        },
        {
            "id": "task847-1b35ac6ed10445d69f35c223428f058f",
            "input": "The aim of this prospective, randomized, double-blind study was to compare two doses of intranasal sufentanil for postoperative analgesia, titrated according to individual requirements based upon a numeric rating scale (NRS) from 0 to 10 for pain.', 'Forty patients, American Society of Anesthesiologists physical status I-II, scheduled for herniorrhaphy or hemorrhoidectomy under general anesthesia, were included when postoperative NRS was > 3. Nurses used a nasal puff device delivering a constant volume. Patients were randomized into two groups: Group A patients received a dose of 0.025 microg x kg(-1) /puff, Group B patients a dose of 0.05 microg x kg(-1) /puff. Puffs were administered as often as needed to obtain NRS < or = 3, with an interval time of five minutes. Hemodynamic, respiratory measures and sedation were recorded every five minutes.', 'The probability of persistence of pain in Group B was consistently lower than in Group A. After 20 min, 20% of the patients had a NRS score > 3 in Group B, as opposed to 60% in Group A. At 60 min, no patient had a NRS > 3 in Group B, whereas there was a probability of 20% to record a NRS > 3 for Group A. Hemodynamic, respiratory parameters and sedation remained stable with no intergroup differences.",
            "output": [
                "Is intranasal sufentanil effective for postoperative analgesia in adults?"
            ]
        },
        {
            "id": "task847-6cc1c22759e740098d5b3e16eb09b922",
            "input": "Analgesia and sedation, routinely used as adjunct medications for regional anesthesia, are rarely used in the pregnant patient because of concerns about adverse neonatal effects. In an effort to obtain more information about maternal analgesia and sedation we studied neonatal and maternal effects of iv fentanyl and midazolam prior to spinal anesthesia for elective Cesarean section.', 'In this double-blinded, randomized, placebo-controlled trial, 60 healthy women received either a combination of 1 microg x kg(-1) fentanyl and 0.02 mg x kg(-1) midazolam intravenously or an equal volume of iv saline at the time of their skin preparation for a bupivacaine spinal anesthetic. Sample size was based on a non-parametric power analysis (power > 0.80 and alpha = 0.05) for clinically important differences in Apgar scores. Fetal outcome measures included Apgar scores, continuous pulse oximetry for three hours, and neurobehavioural scores. Maternal outcomes included catecholamine levels, and recall of anesthesia and delivery.', 'There were no between-group differences of neonatal outcome variables (Apgar score, neurobehavioural scores, continuous oxygen saturation). Mothers in both groups showed no difference in their ability to recall the birth of their babies.",
            "output": [
                "Do a single dose of fentanyl and midazolam prior to Cesarean section have no adverse neonatal effects?"
            ]
        },
        {
            "id": "task847-b6b2aaf7fa3c4475992d76cbdc28a334",
            "input": "Ideally, preoxygenation is performed using a tight fitting mask either by breathing normally for three to five minutes or with four to eight vital capacity (VC) breaths in 0.5 to one minute, but in practice leaks are frequent and sometimes unavoidable. This study was designed to determine which breathing method provided the best oxygenation in the presence of leak.', 'Twenty volunteers were instructed to breathe from a circle circuit supplied with 6 L x min(-1) of fresh oxygen. Each subject was tested under four situations selected in random order: 1) normal breathing for three minutes without leak; 2) normal breathing for three minutes with a leak; 3) four VCs in 30 sec without a leak; and 4) four VCs in 30 sec with a leak. The leak was created by a piece of size 18 French nasogastric tube, 5 cm long, taped under the face mask. Inspired and expired O(2) and CO(2) were sampled at the nostrils.', 'In the absence of a leak, the end-tidal oxygen fraction (F(EO(2)) was greater after three minutes of tidal breathing (89 +/- 3%; mean +/- SD) in comparison with the response to four VCs (76 +/- 7%; P < 0.001). Introduction of a leak decreased the F(EO(2)) significantly (P < 0.001). With a leak, the F(EO(2)) was similar with normal breathing (61 +/- 8%) and after four VCs (59 +/- 11%).",
            "output": [
                "Is when a leak unavoidable , preoxygenation is equally ineffective with vital capacity or tidal volume breathing?"
            ]
        },
        {
            "id": "task847-61f6811d44c344b7b9346908afbf4697",
            "input": "The host genetic background to develop primary gastric B-cell lymphoma in patients with chronic Helicobacter pylori infection is unknown. Tumor necrosis factor (TNF)-alpha plays a key role in H. pylori-associated inflammation and appears to be involved in the evolution of lymphoproliferative disorders. We investigated four functional promotor polymorphisms in the TNF-alpha gene for association with the development of primary gastric B-cell lymphoma.', 'A total of 144 lymphoma patients, 595 H. pylori-infected controls and 534 healthy blood donors were genotyped for TNF-alpha-238, -308, -857, and -1031 by Taqman technology and case-control analysis was conducted.', \"There was no significant difference in allele and genotype frequencies in H. pylori-infected patients and healthy controls. TNF-857 T allele was found in 15.1% of patients with low-grade lymphoma and 9.1% of H. pylori-infected patients (Pearson's=5.7, p=0.017, OR=1.8, Wald 95% CI: 1.1< O.R.< 2.8). Carrier of the rare allele T had a 1.8-fold increased risk to develop low-grade lymphoma (Pearson's=5.4, p=0.021). Patients with high-grade lymphoma were significantly more frequent carriers of the TNF-857 T allele than healthy blood donors (30.9%vs 18.9%, Pearson's=4.5, p=0.033). Carriage of the T allele conferred a 1.9-fold increased risk (Wald 95% CI: 1.0<O.R.< 3.6). There were no associations found between any of the SNPs and disease progression.",
            "output": [
                "Is a functional promotor polymorphism of TNF-alpha associated with primary gastric B-Cell lymphoma?"
            ]
        },
        {
            "id": "task847-95c53b12c12742ebb36f9b97188a6d0a",
            "input": "Constitutive activation of signal transducer and activator of transcription 3 (Stat3) protein has been observed in a wide variety of tumors, including breast cancer, and contributes to oncogenesis at least in part by prevention of apoptosis. In a study of 45 patients with high-risk breast cancer enrolled in a phase II neoadjuvant chemotherapy trial with docetaxel and doxorubicin, we evaluated the levels of Stat3 activation and potentially associated molecular biomarkers in invasive breast carcinoma compared with matched nonneoplastic tissues.', 'Using immunohistochemistry and image analysis, we quantified the levels of phospho-Stat3 (pY-Stat3), phospho-Src (pY-Src), epidermal growth factor receptor, HER2/neu, Ki-67, estrogen receptor, Bcl-2, Bcl-xL, Survivin, and apoptosis in formalin-fixed, paraffin-embedded sections from invasive carcinomas and their paired nonneoplastic parenchyma. The levels of molecular biomarkers in nonneoplastic and tumor tissues were analyzed as continuous variables for statistically significant correlations.', 'Levels of activated pY-Stat3 and pY-Src measured by immunohistochemistry were significantly higher in invasive carcinoma than in nonneoplastic tissue (P < 0.001). In tumors, elevated levels of pY-Stat3 correlated with those of pY-Src and Survivin. Levels of pY-Stat3 were higher in partial pathologic responders than in complete pathologic responders. In partial pathologic responders, pY-Stat3 levels correlated with Survivin expression.",
            "output": [
                "Is activation of stat3 in primary tumors from high-risk breast cancer patients associated with elevated levels of activated SRC and survivin expression?"
            ]
        },
        {
            "id": "task847-e8486e3d765447a0a4d1aca1295162c0",
            "input": "There is no reliable serum marker available to monitor incipient pancreas or islet-cell rejection. We tested the hypothesis that quantification of donor-specific genomic DNA in serum (from tissue damage) can serve as a marker of rejection.', 'Using a recently developed panel of HLA-specific quantitative PCR assays (Q-PCR), we tested 158 sera from 42 pancreas-kidney transplant recipients. Temporally related biopsies for 65 sera permitted analysis for correlation of donor DNA concentrations with rejection.', 'Donor DNA concentrations were higher in sera from recipients who had experienced allograft rejection (n = 31) than from those who had not (n = 34). Median concentrations, expressed as the genome-equivalent (gEq) number of donor cells per 10(6) host cells, were 2613 and 59 gEq/10(6), respectively (P = 0.03).",
            "output": [
                "Do soluble donor DNA concentrations in recipient serum correlate with pancreas-kidney rejection?"
            ]
        },
        {
            "id": "task847-f8c555655b044b4fac7415b52033af78",
            "input": "Consultant gynecologic oncologists from the regional Comprehensive Cancer Center assisted community gynecologists in the surgical treatment of patients with ovarian carcinoma when they were invited. For this report, the authors evaluated the effects of primary surgery by a gynecologic oncologist on treatment outcome.', \"The hospital files from 680 patients with epithelial ovarian carcinoma who were diagnosed between 1994 and 1997 in the northern part of the Netherlands were abstracted. Treatment results were analyzed according to the operating physician's education by using survival curves and univariate and multivariate Cox regression analyses.\", 'Primary surgery was performed on 184 patients by gynecologic oncologists, and on 328 patients by general gynecologists. Gynecologic oncologists followed surgical guidelines more strictly compared with general gynecologists (patients with International Federation of Gynecology and Obstetrics [FIGO] Stage I-II disease, 55% vs. 33% [P=0.01]; patients with FIGO Stage III disease, 60% vs. 40% [P=0.003]) and more often removed all macroscopic tumor in patients with FIGO Stage III disease (24% vs. 12%; P=0.02). When patients were stratified according to FIGO stage, the 5-year overall survival rate was 86% versus 70% (P=0.03) for patients with Stage I-II disease and 21% versus 13% (P=0.02) for patients with Stage III-IV disease who underwent surgery by gynecologic oncologists and general gynecologists, respectively. The hazards ratio for patients who underwent surgery by gynecologic oncologists was 0.79 (95% confidence interval [95%CI], 0.61-1.03; adjusted for patient age, disease stage, type of hospital, and chemotherapy); when patients age 75 years and older were excluded, the hazards ratio fell to 0.71 (95% CI, 0.54-0.94) in multivariate analysis.",
            "output": [
                "Does surgery by consultant gynecologic oncologists improve survival in patients with ovarian carcinoma?"
            ]
        },
        {
            "id": "task847-f68b90adbadf44b5b759eb3af607c9a3",
            "input": "There is a lot of evidence that angina during the 24-48 h before a reperfused myocardial infarction improves the evolution of the patients. However, there are studies that failed to demonstrate this protective effect of preinfarction angina in an interventional reperfusion setting.', 'To compare the effect of preinfarction angina (PIA) on inhospital evolution of thrombolysis vs. interventionally reperfused acute myocardial infarction (AMI).', 'There were prospectively studied 133 consecutive AMI patients, eligible for reperfusion (thrombolysis or interventional). History of PIA under 48 hours was obtained. Evolution of AMI was evaluated considering the following end-points: the ratio between the number of ECG leads with final pathologic Q wave and the number of leads with initial ST elevation, CK-MB values, separate and composite incidence of death, heart failure, shock and incidence of serious arrhythmia (sustained VT or ventricular fibrillation).', 'ECG ratio was lower in patients with PIA (0.511 +/- 0.281 vs. 0.646 +/- 0.274, p=0.02) in thrombolysed patients, but it was higher in interventionally reperfused patients (0.740 +/- 0.418 vs. 0.554 +/- 0.295 p=0.11). CK-MB values were lowered by PIA in thrombolysed AMI (122 +/- 74 vs. 190 +/- 89, p=0.0003), but they were not in the interventional group. Clinical end-points were slightly less frequent in patients with PIA, in both reperfusion groups, but not statistically significant. Major arrhythmia occurred less frequently in interventionally reperfused patients with PIA (9.5% vs. 31.6%, p=0.12).",
            "output": [
                "Does prodromal angina reduce infarcted mass less in interventionally reperfused than in thrombolysed myocardial infarction?"
            ]
        },
        {
            "id": "task847-53185f4d8ea94315ae7228abdb756003",
            "input": "The engagement of the T cell receptor results in actin cytoskeletal reorganization at the immune synapse (IS) and the triggering of biochemical signaling cascades leading to gene regulation and, ultimately, cellular activation. Recent studies have identified the WAVE family of proteins as critical mediators of Rac1-induced actin reorganization in other cell types. However, whether these proteins participate in actin reorganization at the IS or signaling pathways in T cells has not been investigated.', 'By using a combination of biochemical, genetic, and cell biology approaches, we provide evidence that WAVE2 is recruited to the IS, is biochemically modified, and is required for actin reorganization and beta-integrin-mediated adhesion after TCR crosslinking. Moreover, we show that WAVE2 regulates calcium entry at a point distal to PLCgamma1 activation and IP(3)-mediated store release.",
            "output": [
                "Does the WAVE2 complex regulate actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation?"
            ]
        },
        {
            "id": "task847-2045a0becba9426791472bc0c0eeaecc",
            "input": "During colitis, epithelial function is impaired, leading to increased bacterial translocation. Recent studies have shown the important role of proinflammatory cytokines and chemokines, including RANTES (regulated on activation, normal T-cell expressed and secreted), in inflammatory bowel diseases (IBDs). In this study, we evaluated the role of Met-RANTES, an antagonist of the RANTES receptor, on the impairment of bacterial translocation in a rat model of colitis.', 'Rats were randomly assigned to 3 groups. Group 1 = control, group 2 = experimental colitis, and group 3 = colitis plus Met-RANTES treatment. On day 7 after colitis was induced, plasma tumor necrosis factor-alpha colon tissue myeloperoxidase and portal blood endotoxin levels were measured. Lymph node, liver, and spleen culture quantified bacterial translocation.', 'Met-RANTES treatment resulted in significant decreases in colonic damage as well as bacterial translocation in experimental colitis.",
            "output": [
                "Does treatment with Met-RANTES decrease bacterial translocation in experimental colitis?"
            ]
        },
        {
            "id": "task847-1b43cc9e517340fca09b6461726fd2ff",
            "input": "To determine whether rubella virus (RV) is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI).', 'Retrospective patient-controlled study.', 'Intraocular immunoglobulin G production against RV, herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii was determined in the aqueous humor of 14 patients with FHI, 13 control subjects with herpetic uveitis anterior, and 19 control subjects with ocular toxoplasmosis by calculation of the Goldmann-Witmer coefficient (GWC).', 'All patients and control subjects were seropositive for RV. Intraocular antibody production (GWC >3) against RV was found in 13 of 14 patients (93%) with FHI. Intraocular antibody production against HSV, VZV, or T gondii was not detected. None of the control subjects with herpetic uveitis anterior or with toxoplasma chorioretinitis had a positive GWC for rubella virus (P < .0001, Fisher exact test).",
            "output": [
                "Is rubella virus associated with fuchs heterochromic iridocyclitis?"
            ]
        },
        {
            "id": "task847-c25c910fbe4441f9b39d3ffa0a4f24c7",
            "input": "This study's objective was to determine the test characteristics of pedal pulse palpation in the diagnosis of peripheral arterial disease (PAD) when compared to the more widely recommended screening tool, the ankle-brachial index (ABI).\", 'We screened patients > 50 years of age for PAD within primary care clinics in Houston. PAD was diagnosed by an ABI of <0.9. At each visit, pedal pulse palpation was performed for each leg. Of the patients who screened positive for PAD by ABI, we determined the sensitivity, specificity, and positive predictive value of pulse palpation.', 'We enrolled 403 patients with a mean age of 63.8 +/- .36 years. The prevalence of PAD was 16.6% (67 patients total). Of the 45 patients with disease involving their left leg, 37 (82.2%) had a palpable pulse. Of the 37 patients with disease involving their right leg, 25 (67.6%) had a palpable pulse. The sensitivity of a non-detectable pulse for the diagnosis of PAD was 17.8% and 32.4% for the left leg and the right leg, respectively. The specificity of pulse palpation for the detection of PAD was 98.7% and 97.8% for the left leg and the right leg, respectively.",
            "output": [
                "Is an absent pulse sensitive for the early detection of peripheral arterial disease?"
            ]
        },
        {
            "id": "task847-8a60597262f2492889bf290655928b15",
            "input": "The aim of the study was to evaluate the prevalence of the GP Ia and GP IIIa polymorphisms in the group of women in labor, and to assess the risk of thrombosis associated with their occurrence.', '245 women in labor hospitalized between 1.01.2001 and 31.12.2003 r. were enrolled in the study. Patients were qualified for the study if detailed physical exam and past medical history excluded existence of known risk factors predisposing to thrombosis. Study group was composed of 72 women in childbirth, which at some point during current pregnancy or in early labor were diagnosed with thrombosis, and control group included 173 women in labor randomly picked from the group of patients with uncomplicated pregnancies. Polymorphic regions of platelets glycoprotein were detected using genotyping methods based on polymerase chain reactions (PCR).', '1.72% of patients were found to have thrombosis. The thrombosis was located in the venous system in 97.2% of cases. Arteries were affected in two patients (2.7%). Prevalence of individual platelets glycoprotein mutations did not differ between controls and study group. In both groups platelets glycoprotein polymorphisms moderately pro-thrombotic A1/A2 and C/T dominated, and the least numerous were strongly pro-thrombotic A2/A2 and T/T.",
            "output": [
                "Does polymorphism of the glycoprotein Ia and IIIa in the group of women in childbirth correlate with an increased risk of developing thrombosis?"
            ]
        },
        {
            "id": "task847-cc3eb186332d499aa52b18938a13c1e4",
            "input": "Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The aim of the present study was to investigate the role of CALPAIN-5 (CAPN5) gene in PCOS susceptibility.', 'We analysed four intronic polymorphisms of the CAPN5 gene in 148 well-characterized women with PCOS and 606 unrelated controls. We performed a case-control study and an intracohort analysis of clinical characteristics associated with PCOS.', 'Analysis of haplotypes distribution between PCOS population compared to controls showed a strong deviation (P = 0.00029). The haplotypes GGCA and GGTG were overrepresented in PCOS patients (P = 0.009 and P = 0.001, respectively). In addition, we identified several CAPN5 haplotypes associated with phenotypic differences observed between PCOS patients, such as the presence of obesity (P = 0.02), cardiovascular complications (P = 0.02), familial antecedents of obesity (P = 0.003) and of hypertension (P = 0.007) and type 2 diabetes mellitus aggregation (P = 0.04).",
            "output": [
                "Are specific haplotypes of the CALPAIN-5 gene associated with polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-b70ca151a6af4601b4798147a39c79da",
            "input": "To assess the relationship between infarct-related artery (IRA) stenosis and capillary density and to assess its effect on scar formation in the human heart.', 'Morphometric evaluation was performed in 51 human hearts, as follows. Group I non-cardiac death (control), Group II post-Q-wave myocardial infarction (QMI) death and Group III patients who survived QMI and who underwent aneurysmectomy. Using morphometric parameters, the relationship between left ventricle (LV) mass, infarct size, IRA stenosis, cellular hypertrophy and changes in microcirculation were analyzed within the infarcted area and free LV wall.', 'A significant reduction in capillary density within the infarcted area was noted in group II when compared to the control group (1525.6+/-378.5/mm(2) vs. 2968.7+/-457.3/mm(2); p<0.001). Reduction in capillary density was inversely related to infarct size (r=-0.616; p=0.006) and degree of IRA stenosis (r(S)=-0.512; p=0.03). The most significant reduction in capillary density was observed in patients with total IRA occlusion (1204.6+/-156.9/mm(2) vs. 1676.6+/-245.8/mm(2); p<0.001). Similarly, a reduction in capillary density of over 60% (1030.7+/-241.8/mm(2)) was observed within aneurysms resected surgically.",
            "output": [
                "Is chronic infarct-related artery occlusion associated with a reduction in capillary density . Effects on infarct healing?"
            ]
        },
        {
            "id": "task847-232d6dc93f0e4bb1b6116be2ae0214af",
            "input": "Obesity and diabetes are major risk factors for cholesterol gallstones, and the majority of obese people are leptin-resistant. Our previous work has shown that both leptin-deficient (Lepob) and leptin-resistant (Lepdb) obese diabetic mice have decreased in vitro gallbladder motility. Leptin administration to leptin-deficient (Lepob) animals restores gallbladder motility and reverses obesity and hyperinsulinemia. However, additional leptin in leptin-resistant obesity would not be expected to improve obesity-related parameters. Recent studies demonstrate that ciliary neurotrophic factor (CNTF) reduces weight and hyperinsulinemia in leptin-resistant obesity. Our hypothesis is that CNFT would cause weight loss, lower blood sugars, and restore gallbladder contractility in leptin-resistant (Lepdb) mice.', '20 C57b/6J and 20 Lepdb 8-week-old female mice were injected daily with either intraperitoneal saline or 0.3 microg/g CNTFAx15 for 17 days. Gallbladders were mounted in muscle baths and stimulated with acetylcholine, neuropeptide Y, and cholecystokinin. Gallbladder volume, serum glucose, insulin, liver weight, liver fat, and gallbladder responses were measured. Data were analyzed by ANOVA.', 'Saline treated obese mice had greater body weight and obesity parameters, but decreased gallbladder contractility to neurotransmitters compared to saline treated lean mice. CNTF administration to obese mice decreased body weight and obesity parameters, and restored gallbladder contractility. CNTF treated lean animals had weight loss and decreased gallbladder contraction to acetylcholine and cholecystokinin compared to saline treated lean animals.",
            "output": [
                "Does ciliary neurotrophic factor restore gallbladder contractility in leptin-resistant obese diabetic mice?"
            ]
        },
        {
            "id": "task847-0d9f72ff7a3140c4a142be795f395d86",
            "input": "To present a novel method for analyzing the voltage waveform from high-frequency X-ray generators for radiographic systems.', 'The output signal of the actual voltage across the tube of a high-frequency generator was measured using the built-in voltage sense taps that are used for voltage regulation feedback in X-ray generators. The output signal was stored in an analyzing recorder, and the waveforms were analyzed using FFT analysis. The FFT analysis of high-frequency generators consisted of obtaining the power spectrum, comparing the major frequency components in the tube voltage waveforms, and examining the intensity of each frequency component.', 'FFT analysis enables an objective comparison of the complex tube voltage waveforms in high-frequency X-ray generators. FFT analysis detected the change in the X-ray tube voltage waveform that occurred when there were problems with the high-frequency generator.",
            "output": [
                "Do fFT analysis of the X-ray tube voltage waveforms of high-frequency generators for radiographic systems?"
            ]
        },
        {
            "id": "task847-700d6622e5334425b12f9f8d94dd082a",
            "input": "Crohn's disease is a heterogeneous inflammatory bowel disease. The impact of age at diagnosis on the clinical course of patients varies widely as reported in the Western literature. Using the Vienna Classification, we seek to determine whether young Crohn's disease patients in an Asian population followed a different clinical course than old patients.\", \"The case records of 100 Crohn's disease patients who were treated at the Inflammatory Bowel Disease Center, Singapore General Hospital, were studied retrospectively. The age group and location of disease and behavior according to the Vienna classification were determined at diagnosis.\", 'A1 group (age <40 years) defined as \"young\" and A2 group (age > or =40) defined as \"old\" contained 65 and 35 patients, respectively. Median age for the young group was 27.4 years and that for the old group was 52.6 years. Of the young patients, 66.7% flared at least once compared with 28.6% of the old patients, odds ratio of 5.0 (P < 0.001). Young patients were more likely to be steroid dependent (20.0% of A1 versus 8.6% of A2, P = 0.14), received azathioprine (38.5% of A1 versus 5.7% of A2, P < 0.001) and experienced complications (31% of A1 versus 20% of A2, P = 0.25)-numerically higher rates that did not reach statistical significance. There was no significant difference between the age groups for the location and behavior of disease as well as requirement for surgery.",
            "output": [
                "Does crohn 's disease run a more aggressive course in young Asian patients?"
            ]
        },
        {
            "id": "task847-0cc5429e783942bf80acf84585cff1b9",
            "input": "Increased medical staff workload has been associated with worse outcomes in several studies. Inappropriate staffing has also been implicated in the increased risk of mortality for medical patients admitted on weekends. A theoretical threshold patient load may exist, beyond which the resources are strained and patient outcomes suffer. The goal of the study was to see whether trauma patients admitted during 'high' patient-load periods, at night, or on weekends had worse outcomes.\", 'Trauma patients admitted to a high-volume Level I trauma center from 1994 to 2002 were analyzed. Patient load was defined as a combination of the number of patients admitted and the severity of their illness. On the basis of a multivariate regression model, a probability of fatal outcome was calculated for each patient as a marker for the severity of illness. For each patient, two new variables were calculated, the number of admissions (#ad) and the average probability of fatal outcome (PFO) for the 24-hour period in which the patient was admitted (excluding the patient him- or herself). The above variables, night/d, and weekend/d were placed in a multivariate regression model.', \"There were 30,686 patients. Age, mechanism of injury, Injury Severity Score, maximum head Abbreviated Injury Scale score, admission Glasgow Coma Scale score, systolic blood pressure, and intubation status were the independent predictors of mortality. This model had an outstanding predictive power, with an area under the receiver operating characteristic curve of 0.96. The mean #ad was 11 +/- 4 and PFO was 0.08 +/- 0.07. Values above the 90th percentile were considered 'high' for #ad > 17 or PFO > 0.18. There was no difference in mortality for patients admitted during high #ad (odds ratio [OR], 0.95; p = 0.7) or high PFO (OR, 0.99; p = 0.9) versus low. There was no difference in mortality if a patient was admitted on weekends versus weekdays (OR, 0.9; p = 0.2) or at night versus day (OR, 0.9; p = 0.2). There was no difference in hospital length of stay for high #ad, high PFO, nights, or weekends.",
            "output": [
                "Do effect of patient load on trauma outcomes in a Level I trauma center?"
            ]
        },
        {
            "id": "task847-e1731cd7637641a988f4ff554b871e8d",
            "input": "Hypotension increases mortality after all types of injuries. Prior studies comparing mortality of hypotensive traumatic brain injury (TBI) patients to normotensive TBI patients have implied that hypotension is particularly detrimental after TBI. It is unknown whether hypotension affects TBI patients more severely than it affects other types of patients. We hypothesized that hypotension does not increase mortality in TBI patients more than it does in non-TBI patients.', 'National Trauma Data Bank (1994-2002) patients aged 18 to 45 years with blunt mechanisms of injury treated at Level I and Level II centers were included. Deaths occurring before 24 hours were excluded. Logistic regression was used to measure the association between hypotension (< or =90 mm Hg) and death after adjusting for confounding variables of age, gender, comorbidities, complications, Glasgow Coma Scale score, and severity of associated injuries. Odds ratios (95% confidence interval) indicate the risk of death in hypotensive patients in each group compared with normotensive patients in the same group.', 'The study population consisted of 79,478 patients (TBI, 30,742; no TBI, 48,736). Hypotension independently quadrupled the risk of death after adjusting for confounding variables (odds ratio [OR], 4.8; 95% confidence interval [CI], 4.1-5.6). However, increase in this risk associated with hypotension was the same in TBI (OR, 4.1; 95% CI, 3.5-4.9) and non-TBI patients (OR, 4.6; 95% CI, 3.4-6.0). Furthermore, the relationship between hypotension and TBI did not change with increasing head Abbreviated Injury Scale score severity.",
            "output": [
                "Does hypotension increase mortality in brain-injured patients more than it does in non-brain-injured Patients?"
            ]
        },
        {
            "id": "task847-b1d32bab444e486799dc6e306c312d31",
            "input": "Various types of diagnostic and monitoring techniques are available in the prehospital environment. It is unclear how increasing complexity of diagnostic equipment improves the ability to predict the need for a life-saving intervention (LSI). In this study, we determined whether the addition of diagnostic equipment improved the predictive power of vital signs and scores obtained only by physical examination.', 'Institutional review board approval was obtained for an analysis of 793 prehospital trauma patient records collected during helicopter transport by Emergency Medical Services personnel. Exclusion of severe head injuries and patients with incomplete data resulted in 381 patients available for analysis. Data sets were classified on the basis of the instrumentation requirements for capturing the given measurements and were defined by three groups: Group 1, vital signs obtained with no equipment (radial, femoral, and carotid pulse character; capillary refill; motor and verbal components of the Glasgow Coma Scale [GCS]); Group 2, Group 1 plus eye component of the GCS and pulse oximetry (Spo(2)); and Group 3, Group 2 plus fully automated noninvasive blood pressure measurements, heart rate, end-tidal carbon dioxide, and respiratory rate. LSIs performed during transport and in the hospital were recorded. Data were analyzed using a multivariate logistic regression model to determine which vital signs were the best predictors of LSI.', 'Radial pulse character and GCS verbal and motor components had the best predictive power for the need of a prehospital LSI in Group 1 (receiver operating characteristic [ROC] curve, 0.97). Radial pulse character together with the eye component of the GCS and the motor component of the GCS provided the best prediction of a need for a prehospital LSI for Group 2 (ROC curve, 0.97). Addition of all supplementary vital signs measured by an automated monitor (Group 3) resulted in an ROC curve of 0.97. Given an abnormal radial pulse character (weak or absent) and abnormal GCS verbal and motor components, the probability of needing an LSI was greater than 88%.",
            "output": [
                "Do manual vital signs reliably predict need for life-saving interventions in trauma patients?"
            ]
        },
        {
            "id": "task847-0b3b1c8967a04ea58cb97df82376c03e",
            "input": "Primary graft dysfunction caused by ischemia-reperfusion injury is one of the most frequent causes of early morbidity and death after lung transplantation. We hypothesized that the perioperative management with aprotinin decreases the incidence of allograft reperfusion injury and dysfunction after clinical lung transplantation.', \"Lung transplant databases of two transplant centers were used to investigate the incidence of severe post-transplant reperfusion injury (PTRI). We examined data of 142 patients who underwent either single lung (81) or bilateral sequential lung (61) transplantation for COPD, idiopathic pulmonary fibrosis, cystic fibrosis, and miscellaneous lung disorders between 1997 and 2000. Thirty patients were excluded due to heart-lung transplantation or lung transplantation for Eisenmenger's disease, re-transplantation, rejection, or deviation from the standardized triple immunosuppression protocol. The data of remaining 112 patients (control group, 64% single lung, 36% sequential bilateral lung transplants) were compared to the prospectively collected data of 59 lung transplant patients over the last 5 years. All of these 59 patients were managed perioperatively with aprotinin infusion. In addition, Euro-Collins-aprotinin procurement solution (Apt-EC group) was used for 50 donor lungs (58% single lung, 42% sequential bilateral lung transplants). Aprotinin in combination with low-potassium dextran (LPD) flush solution (Apt-LPD group) was used for the procurement of 34 lungs (59% single lung, 41% sequential bilateral lung transplants). The International Society of Heart and Lung Transplantation (ISHLT) grade III injury score was used for the diagnosis of severe PTRI, which is based on a PaO(2)-FIO(2) ratio of less than 200 mmHg.\", 'Severe reperfusion injury grade III was observed in 18% of the control group. ECMO support was required in 25% of these patients. The associated mortality rate was 40%. Correlating factors for PTRI were donor age greater than 35 years (45%, p=0.01, mean age 38+/-8) and recipient pulmonary artery systolic pressure greater than 60 mmHg (48%, p<0.05). Lung graft ischemic times (231+/-14 min) and intraoperative techniques (cardiopulmonary bypass in 12%) were not associated with negative outcomes. Despite longer ischemic times (258+/-36 min and 317+/-85 min, respectively) and older donors (42+/-12 years and 46+/-12 years, respectively) in the aprotinin patient groups (Apt-EC and Apt-LPD group), the incidence of PTRI was markedly lower (6% and 9%, respectively). There was no mortality in the Apt-EC group and one patient died in the Apt-LPD group due to PTRI-induced graft failure.",
            "output": [
                "Does aprotinin decrease reperfusion injury and allograft dysfunction in clinical lung transplantation?"
            ]
        },
        {
            "id": "task847-c87e90ffc03f4bc0886176d83136be1f",
            "input": "To examine a population-based cohort for the association between clinicopathologic predictors of survival and immunohistochemical markers (IHC), and to assess changes in gene expression that are associated with lymphovascular invasion (LVI).', 'LVI has been associated with poor survival and aggressive tumor behavior. The molecular changes responsible for the behavior of gastric cancer have yet to be determined. Characterization of IHC markers and gene expression profiles may identify molecular alterations governing tumor behavior.', ': Clinicopathologic and survival data of 114 patients were reviewed. Archival specimens were used to construct a multitumor tissue array that was subjected to IHC of selected protein targets. Correlation of IHC with tumor thickness (T status), LVI and prognosis was studied. Microarray analysis of fresh gastric cancer tissue was conducted to examine the gene expression profile with respect to LVI.', 'In a multivariate analysis, nodal status (N), metastasis (M), and LVI were independent predictors of survival. LVI was associated with a 5-year survival of 13.9% versus 55.9% in patients in whom it was absent. LVI correlated with advancing T status (P = 0.001) and N status (P < 0.001). IHC staining of cyclooxygenase-2 (COX-2) correlated with T status, tumor grade, lymph node positivity, and IHC staining of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Microarray analyses suggested differential expression of oligophrenin-1 (OPHN1) and ribophorin-II (RPNII) with respect to LVI.",
            "output": [
                "Is lymphovascular invasion associated with poor survival in gastric cancer : an application of gene-expression and tissue array techniques?"
            ]
        },
        {
            "id": "task847-bdca1ba53c2345b6879ed66eba896d5a",
            "input": "The neuropeptides leptin and ghrelin are involved in the appetite regulating network consisting of distinct orexigenic (ghrelin) and anorexigenic (leptin) circuitries. Recently, it has been shown that elevated leptin levels are associated with alcohol craving in patients suffering from alcoholism. Therefore, the aim of the present pilot study was to determine whether the gut-derived peptide ghrelin which increases hunger and food intake is altered and associated with alcohol craving in alcoholic patients', 'Two types of alcoholic inpatients, group A (active drinker, acutely intoxicated, n=97) and group B (early abstainer, who had stopped drinking 24-72 hrs before, n=21) were consecutively included in a prospective study from the first day of hospitalization. Ghrelin plasma levels and craving data were assessed on days 0, 1, 2 and 7(-10) and compared to those of 24 healthy controls', 'At each time-point ghrelin plasma levels of alcoholic patients were significantly increased compared to healthy subjects. Furthermore, early abstainers showed significantly higher ghrelin levels than active drinkers. In the group of active drinkers ghrelin plasma levels were significantly increased at each time point compared to baseline. No correlations were found between ghrelin levels and craving data measured by the visual analogue scale or the Obsessive Compulsive Drinking Scale",
            "output": [
                "Are ghrelin levels increased in alcoholism?"
            ]
        },
        {
            "id": "task847-0d8d8318202a4d638cb9b3670bafbe63",
            "input": "Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) are controversial and mostly based on a heterologous rat Nb2 cell bioassay. Biological activity of bbPRL observed in vitro but not in vivo may be due to its high molecular weight, preventing its passage through capillary barrier. Alternatively, bbPRL bioactivity may differ depending on the prolactin (PRL) receptor (PRLR) species specificity.', 'The objective of the study was to characterize the bioactivity of bbPRL in a homologous bioassay: Ba/F-3 cells stably expressing the human PRLR.', \"Chromatography-purified bbPRL from macroprolactinemic individuals (group I, n = 18) and monomeric PRL from hyperprolactinemic patients without macroprolactinemia (group II, n = 5) were tested in Nb2 and Ba/F-LLP bioassays. Both groups were followed up at the neuroendocrinology outpatients' clinic.\", 'Biological activity of bbPRL presented in the two bioassays was measured.', 'In group I, no patient had hypogonadism. Mean ratio bioactivity to immunoactivity of bbPRL in the Nb2 assay was 0.69. There was no dose-response in 15 of the 18 samples tested in Ba/F-LLP assay. In group II, three patients had galactorrhea and all five had hypogonadism. Mean ratio bioactivity to immunoactivity of monomeric PRL samples was 1.35 in Nb2 and 0.91 in Ba/F-LLP assay.",
            "output": [
                "Does human macroprolactin display low biological activity via its homologous receptor in a new sensitive bioassay?"
            ]
        },
        {
            "id": "task847-3eb57bfc052d4ec39d298779ef88cc9a",
            "input": "Dual activation by TSH of the phospholipase C and cAMP cascades has been reported in human thyroid cells. In contrast, Singh et al. reported convincing data in FRTL-5 thyrocytes arguing against such an effect in this model. Their data in FRTL-5 cells indicated no increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in response to TSH. Therefore, the authors questioned results previously obtained on human cells by cruder methodology.', 'We investigated the formation of inositol phosphates by HPLC techniques in human thyroid slices to separate the inositol phosphate isomers.', 'Ins(1,4,5)P3, inositol 1,3,4-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate were increased after TSH stimulation. The effect of TSH in human thyroid cells was reproduced by recombinant TSH and prevented by antibodies blocking the TSH receptor. Thyroid-stimulating antibodies at concentrations eliciting a cAMP response equivalent to TSH failed to stimulate inositol phosphate generation.",
            "output": [
                "Does thyrotropin stimulate the generation of inositol 1,4,5-trisphosphate in human thyroid cells?"
            ]
        },
        {
            "id": "task847-fab45fcdff6b470f8cbefa8dc1c46a80",
            "input": "Absenteeism from outpatient appointments is common. Telephone appointment-reminder calls reduce outpatient-appointment absenteeism in many clinic settings.', 'To determine if telephone appointment-reminder calls reduce outpatient absenteeism at a hospital-based pulmonary function laboratory.', 'We conducted a retrospective review of our pulmonary function laboratory\\'s outpatient appointment records from April to November 2004. Data were collected from consecutive outpatient appointments, including patient age, sex, whether a telephone appointment-reminder call was successfully made, and whether the patient showed up for the scheduled test. We performed 3 analyses. Differences in absenteeism between the groups was the primary outcome measure. First, appointments were separated into 2 groups: (1) appointments for which a reminder call was attempted (\"called\" group) and (2) appointments for which a reminder call was not attempted (\"not-called\" group). The appointments were then separated into 2 further groups: (1) the reminder call was successfully achieved (\"contacted\" group) and (2) the patient either was not called or was called but could not be reached (\"not-contacted\" group). Finally, the contacted group was separated into 2 further groups: (1) reminder calls that resulted in direct conversation with an appropriate person at the patient\\'s listed telephone number, and (2) reminder message left on an answering machine.', 'Data were collected from 515 consecutive outpatient appointments; 45 (8.7%) of these patients did not show up for testing. The absentee rate was 4.7% (n = 10) in the called group and 11.6% (n = 35) in the not-called group (p = 0.0066). In the called group, 6.5% (n = 14) could not be reached. The absentee rate was 4% (n = 8) in the contacted group and 11.7% (n = 37) in the not-contacted group (p = 0.0021). We found no difference in absenteeism between patients who received reminders via direct conversation (4.2%) and those who had a reminder message left on an answering machine (3.7%) (p > 0.05).",
            "output": [
                "Does the effect of telephone appointment-reminder call on outpatient absenteeism in a pulmonary function laboratory?"
            ]
        },
        {
            "id": "task847-a611dfe233514fbd88b24a9510ae2990",
            "input": "When the right atrium (RA) cannula is connected to the venous return line of the cardiopulmonary bypass (CPB) circuit, air is often introduced. Air in the venous cannula may increase cerebral air embolization at initiation of CPB despite the arterial line filter. We measured the volume of air present in the venous cannula after cannulation of the RA. Transcranial Doppler quantified emboli as high-intensity transient-signals (HITS) in both middle-cerebral arteries (MCA) at the beginning of CPB.', \"After RA cannulation, the air column in the venous line was measured and the total volume calculated using the known lumen diameter. CPB onset was defined as the instant when the CPB machine started moving the patient's blood from the RA into the venous reservoir. Starting from CPB onset, HITS were counted: (a) until completion of the first minute on CPB (1-min count) and (b) until aortic cross clamping (pre-clamping count).\", 'We studied 135 patients during coronary artery bypass surgery operated on by 10 cardiac surgeons. HITS during onset of CPB were detected in 95% of patients. Median counts were 10 HITS (25th, 75th percentiles: 3, 26) at 1-min and 21 HITS (8, 51) during pre-clamping. A significant correlation was found between the volume of air in the venous cannula and the HITS counts (r=0.524, p<0.0001). Absence of retained air was associated with lower HITS counts [3 HITS (1, 11)] compared with any amount of air [13 HITS (4, 29), p=0.002)]. The volume of air in the venous cannula, the MCA mean blood flow velocity and the pre-clamping time were the only independent predictors of the pre-clamping HITS counts (p<0.001).",
            "output": [
                "Does residual air in the venous cannula increase cerebral embolization at the onset of cardiopulmonary bypass?"
            ]
        },
        {
            "id": "task847-1f0d590414ac470382fdbe30c9733747",
            "input": "After aortic valve replacement, the effects of a small functional prosthesis on the extent and pattern of regression of left ventricular hypertrophy and on clinical outcomes may be less significant in older patients with low cardiac output requirements. The objective of this study was therefore to determine whether patient-prosthesis mismatch affects left ventricular mass regression in the elderly.', 'The population studied was made up of 88 patients over 65 years of age with pure aortic stenosis who underwent mechanical aortic valve replacement. The effective orifice area index was calculated for each patient on the basis of the projected prosthesis in vivo effective orifice area. It was considered a continuous variable and influence of its entire range of values on the extent of left ventricular mass regression was analyzed in a multivariate prediction model.', 'Even though, in the group with prosthesis-patient mismatch there was a trend for lower postoperative left ventricular mass index (115+/-24 g/m(2) vs 102+/-27 g/m(2), p=0.24) and postoperative peak trans-prosthetic gradients (32+/-9.8 mmHg vs 28.9+/-7.79 mmHg, p=0.35) these differences were not statistically significant. The prevalence of residual left ventricular hypertrophy at follow-up was 50% in the group with patient-prosthesis mismatch and 50% in the group without patient-prosthesis mismatch (p=0.83). In multivariate analysis the only factors associated with indexed left ventricular mass were the follow-up time (p=0.015, r(2)=0.22) and preoperative indexed left ventricular mass (p=0.0012, r(2)=0.11).",
            "output": [
                "Does indexed effective orifice area after mechanical aortic valve replacement affect left ventricular mass regression in elderly?"
            ]
        },
        {
            "id": "task847-a09e519f24ef41dbab59163e1483754b",
            "input": "To avoid the use of unnecessary broad-spectrum antibiotics, empirical therapy of bacteraemia should be adjusted according to the results of blood cultures.', 'To investigate whether the results of blood cultures led to changes in antibiotic use and costs in a tertiary-care university hospital in Norway.', 'Medical records from all patients with positive blood cultures in 2001 were analysed retrospectively. Factors predisposing to infections, results of blood cultures, antibiotic use and outcome were recorded. The influence of blood culture results on antibiotic treatment and costs were analysed.', 'The antibiotic use in 226 episodes of bacteraemia in 214 patients was analysed. According to the guidelines empirical antibiotic treatment should be adjusted in 166 episodes. Antibiotic use was adjusted in 146 (88%) of these 166 episodes, which led to a narrowing of therapy in 118 (80%) episodes. Compared with empirical therapy there was a 22% reduction in the number of antibiotics. Adjustment of therapy was more often performed in Gram-negative bacteraemia and polymicrobial cultures than in Gram-positive bacteraemia. In bacteraemia caused by ampicillin-resistant Escherichia coli, ampicillin was mostly replaced by ciprofloxacin. The cost for 7 days adjusted therapy in 146 episodes was euro19,800 (23%) less than for 7 days of empirical therapy.",
            "output": [
                "Does adjustment of antibiotic treatment according to the results of blood cultures lead to decreased antibiotic use and costs?"
            ]
        },
        {
            "id": "task847-f52a9e5cf90c4207af96de65c684d70a",
            "input": "The antibacterial activity of antimicrobial peptides is influenced by various factors such as salt content, pH and the presence of proteins. In this study, we explored the antibacterial action of the human cathelicidin LL-37 in physiologically relevant conditions, i.e. various human wound fluids, human plasma fractions and serum.', 'Radial diffusion assays using Staphylococcus aureus and Escherichia coli were employed for the study of antibacterial effects of LL-37 in the presence of 12 different wound fluids, citrate-, heparin- or EDTA-plasma, or human serum. Glycosaminoglycan content of wound fluids was determined by an Alcian Blue-binding assay. Protein content of wound fluids was measured by the Bradford method. A slot-binding assay was used to study the effects of inhibitors on the interaction between LL-37 and glycosaminoglycans.', 'Five of twelve wound fluids derived from acute wounds showed marked inhibitory effects on the antibacterial action of LL-37. The inhibition was significantly correlated with high glycosaminoglycan content in wound fluid. Analogous to these findings, heparin-plasma strongly inhibited the antibacterial effect of LL-37. The interaction between LL-37 and glycosaminoglycans was abrogated by the cationic polymers DEAE-dextran and chitosan, yielding increased activity of LL-37.",
            "output": [
                "Do glycosaminoglycans inhibit the antibacterial activity of LL-37 in biological fluids?"
            ]
        },
        {
            "id": "task847-88e000dc5aa64c9dbe7346182b3352f2",
            "input": "The BXD2 mouse strain spontaneously develops glomerulonephritis and erosive arthritis. The goal of this study was to identify the antigenic target proteins and epitopes and to unravel the mechanisms by which the related conditions arise in BXD2 mice.', 'Individual hybridomas isolated from the spleen of a 10-month-old BXD2 mouse were injected intraperitoneally into nonautoimmune mice for evaluation of pathogenicity of each autoantibody. Autoantigens were immunoprecipitated with the pathogenic autoantibody L3A4. Autoantigens were identified using enzyme-linked immunosorbent assay, Western blotting, 2-dimensional gel electrophoresis, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS) and tandem MS. Antigenic epitopes were determined using a high-throughput epitope mapping method.', 'The production of autoantibodies in BXD2 mice occurred in an orderly progression, with peak levels of autoantibodies to nitrotyrosine (NT)-modified enolase, Ro, alpha-actin, and heat-shock proteins (HSPs) preceding peak levels of antihistone, anti-DNA, and rheumatoid factor. Two monoclonal autoantibodies, L3A4 and T56G10, were identified that could induce immune complexes, renal disease, and/or arthritis. Both L3A4 and T56G10 were polyreactive, and each reacted with separate sets of autoantigens. The antigenic targets of L3A4 consisted of NT-modified enolase, ATP5b, alpha-actin, and Hsp70 family proteins including Hspa5 and Hsp74. The antigenic epitopes of NT-modified enolase and Hspa5 exhibited sequence homology and cross-reactivity, suggesting that epitope spreading may occur through a molecular mimicry mechanism.",
            "output": [
                "Does production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice cause glomerulonephritis and arthritis?"
            ]
        },
        {
            "id": "task847-85a2f2f9711749538eed666fa58c6477",
            "input": "The variable-pitch pulse oximeter is an important intraoperative patient monitor. Our ability to hear its auditory signal depends on its acoustical properties and our hearing. This study quantitatively describes the audio spectrum and sound pressure levels of the monitoring tones produced by five variable-pitch pulse oximeters.', 'We compared the Datex-Ohmeda Capnomac Ultima, Hewlett-Packard M1166A, Datex-Engstrom AS/3, Ohmeda Biox 3700, and Datex-Ohmeda 3800 oximeters. Three machines of each of the five models were assessed for sound pressure levels (using a precision sound level meter) and audio spectrum (using a hanning windowed fast Fourier trans-form of three beats at saturations of 99%, 90%, and 85%).', 'The widest range of sound pressure levels was produced by the Hewlett-Packard M1166A (46.5 +/- 1.74 dB to 76.9 +/- 2.77 dB). The loudest model was the Datex-Engstrom AS/3 (89.2 +/- 5.36 dB). Three oximeters, when set to the lower ranges of their volume settings, were indistinguishable from background operating room noise. Each model produced sounds with different audio spectra. Although each model produced a fundamental tone with multiple harmonic overtones, the number of harmonics varied with each model; from three harmonic tones on the Hewlett-Packard M1166A, to 12 on the Ohmeda Biox 3700. There were variations between models, and individual machines of the same model with respect to the fundamental tone associated with a given saturation.",
            "output": [
                "Do audio spectrum and sound pressure levels vary between pulse oximeters?"
            ]
        },
        {
            "id": "task847-f50a72e198e04c84a9e945d8b13c30b1",
            "input": "To assess the influence of moderate, acute weight loss on on-water rowing performance when aggressive nutritional recovery strategies were used in the two hours between weigh in and racing.', 'Competitive rowers (n = 17) undertook three on-water 1800 m time trials under cool conditions (mean (SD) temperature 8.4 (2.0) degrees C), each separated by 48 hours. No weight limit was imposed for the first time trial--that is, unrestricted body mass (UNR1). However, one of the remaining two trials followed a 4% loss in body mass in the previous 24 hours (WT(-4%)). No weight limit was imposed for the other trial (UNR2). Aggressive nutritional recovery strategies (WT(-4%), 2.3 g/kg carbohydrate, 34 mg/kg Na+, and 28.4 ml/kg fluid; UNR, ad libitum) were used in the first 90 minutes of the two hours between weigh in and performance trials.', 'WT(-4%) had only a small and statistically non-significant effect on the on-water time trial performance (mean 1.0 second, 95% confidence interval (CI) -0.9 to 2.8; p = 0.29) compared with UNR. This was despite a significant decrease in plasma volume at the time of weigh in for WT(-4%) compared with UNR (-9.2%, 95% CI -12.8% to -5.6%; p<0.001).",
            "output": [
                "Does acute weight loss followed by an aggressive nutritional recovery strategy have little impact on on-water rowing performance?"
            ]
        },
        {
            "id": "task847-f8c9f202f91245db8ac82f275beda0d8",
            "input": "To investigate the role of HMG-CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox-LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers.', 'In a double-blind, randomized crossover study, 15 obese diet-treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox-LDL levels were measured fasting and during a euglycaemic-hyperinsulinaemic clamp (approximately 5.5 mmol/l; EHC) and a hyperglycemic clamp (approximately 20 mmol/l; HC). An endothelium-dependent flow-mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S-ICAM, s-VCAM and basal prothrombotic factors were also measured.', 'During cerivastatin treatment, basal circulating ox-LDL levels decreased by 48% (P<0.001) compared with placebo. Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P<0.001) and the increments in FMD correlated with decrements in serum ox-LDL levels (r=0.78, P=0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P<0.05). Basal sICAM-1 and sVCAM-1 levels decreased (P<0.01 and P<0.05, respectively).",
            "output": [
                "Are oxidized-LDL levels changed during short-term serum glucose variations and lowered with statin treatment in early Type 2 diabetes : a study of endothelial function and microalbuminuria?"
            ]
        },
        {
            "id": "task847-933e19d8203044b2ae66aabff9d9b85c",
            "input": "The commonest cause of mortality in patients with Type 2 diabetes is atherothrombosis, which can be related to abnormalities in the coagulation and fibrinolytic pathways, as well as in platelet function. Platelet microparticles (PMPs) may contribute to the prothrombotic state and may promote the progression of atherosclerosis. We hypothesized that PMPs are elevated in Type 2 diabetes and that patients with Type 2 diabetes and clinically apparent atherosclerosis would have the highest levels. Similarly, we hypothesized that soluble plasma P-selectin (sPsel) and CD40L (both molecules which are released by activated platelets), as well as %CD62P (P-selectin) and %CD63 positivity on platelets quantified by flow cytometry, would be highest in patients with Type 2 diabetes and clinically apparent atherosclerotic disease, and might be correlated to PMP levels.', 'Venous blood was obtained from 21 Type 2 diabetic patients without atherosclerotic complications, 18 diabetic patients with clinically apparent atherosclerotic disease and 21 non-diabetic control subjects. PMPs, as well as %CD62P and %CD63 positivity on platelets, were quantified by flow cytometry. sPsel and CD40L were measured using ELISA.', 'Patients with Type 2 diabetes and clinically apparent atherosclerotic disease had the highest PMP (P=0.045) and sPsel (P=0.046) levels, compared with patients without complications (who had intermediate PMP levels) and control subjects. Control subjects had the lowest CD40L levels (P<0.001) when compared with patients with Type 2 diabetes, with no difference in sCD40L levels between the two diabetic subgroups. %CD62P and %CD63 positivity did not differ between the groups. PMP levels correlated with %CD62P positivity (P=0.026) but not to %CD63 positivity (P=0.089), sCD40L (P=0.407) or sP-sel (P=0.163); sCD40L levels did not correlate with any other marker of platelet activation.",
            "output": [
                "Is clinically apparent atherosclerotic disease in diabetes associated with an increase in platelet microparticle levels?"
            ]
        },
        {
            "id": "task847-4b2129665d1e4bc984b30e09d6b37abe",
            "input": "The aim of the present study was to evaluate the efficacy of the Glasgow Aneurysm Score (GAS) in predicting the survival of 5498 patients who underwent endovascular repair (EVAR) of an abdominal aortic aneurysm (AAA) and were enrolled in the EUROpean collaborators on Stent-graft Techniques for abdominal aortic Aneurysm Repair (EUROSTAR) Registry between October 1996 and March 2005.', 'The GAS was calculated in patients who underwent EVAR and was correlated to outcome measurements.', 'The median GAS was 78.8 (interquartile range 71.9-86.4, mean 79.2). Tertile 30-day mortality rates were 1.1 per cent for patients with a GAS less than 74.4, 2.1 per cent for those with a score between 74.4 and 83.6, and 5.3 per cent for patients with a score over 83.6 (P < 0.001). Multivariate analysis showed that GAS was an independent predictor of postoperative death (P < 0.001). The receiver-operator characteristic curve showed that the GAS had an area under the curve of 0.70 (95 per cent confidence interval 0.66 to 0.74; s.e. 0.02; P < 0.001) for predicting immediate postoperative death. At its best cut-off value of 86.6, it had a sensitivity of 56.1 per cent, specificity 76.2 per cent and accuracy 75.6 per cent. Multivariable analysis showed that overall survival was significantly different among the tertiles of the GAS (P < 0.001).",
            "output": [
                "Does glasgow Aneurysm Score predict survival after endovascular stenting of abdominal aortic aneurysm in patients from the EUROSTAR registry?"
            ]
        },
        {
            "id": "task847-dd4a00e154ca49bbb47c2c8f96afa08e",
            "input": "Cerebral embolism from cardiac source is an important cause of stroke, specially in patients younger than 45 years old.', 'To describe the transesophageal echocardiography (TEE) findings in young and non-young stroke patients without any prior evidence of cardiac source for cerebral embolism.', 'Transversal study: 523 patients (267 men and 256 women) with ischemic stroke, without any evidence of cardiac abnormality, underwent to TEE.', 'Ten percent were aged 45 years; or less. Left ventricle hypertrophy, left atrial enlargement, spontaneous contrast in aorta, interatrial septum aneurysm, mitral and aortic valve calcification, aortic valve regurgitation, and atherosclerotic plaques in aorta were significantly more frequent in patients aged more than 45 years; 2.8% of non-young patients had thrombus in left heart.",
            "output": [
                "Does transesophageal echocardiography disclose unexpected cardiac sources of embolus in stroke patients aged more than 45 years?"
            ]
        },
        {
            "id": "task847-960d24f58852426f96b36d859f89def8",
            "input": "Environmental and socio-demographic factors can influence the variation of the human sex ratio at birth (SRB = the ratio of males to males plus females). In particular, findings of seasonal, parental education, birth order, and maternal age effects on the SRB are not always in agreement, and a number of works report minimal variation.', 'Here, we investigated the seasonality of SRB in academic and non-academic mothers employed at the University of Vienna, and who gave birth between 1963 and 2000 (n = 1932 births).', 'All data were available from an anonymous employee database.', \"Both groups, academic and non-academic mothers do not differ between their overall SRB. In academic mothers the SRB is significantly (P = 0.004) increased during the springtime and decreased during the summertime. Although in non-academic mothers the trend is comparable, it is far less pronounced and not significant (P = 0.345). When a multiple logistic model was applied to the data of academic mothers the only significant influencing factor on the SRB is the season, while birth order of children and mothers' age at childbirth has no effect. None of the three independent variables influence the SRB in non-academic mothers.\", 'These findings suggest a more flexible SRB rate in academic mothers than in non-academics within the seasons.",
            "output": [
                "Do academic mothers have a pronounced seasonal variation in their offspring sex ratio?"
            ]
        },
        {
            "id": "task847-dcadb78c46cc4f0c8ef435908ea30d8f",
            "input": "It has already been demonstrated that the rat esophagus produces retinoic acid from retinol. In this study, this process is further characterized and the effect of acetaldehyde examined to elucidate the possible mechanisms behind the epidemiological evidence that the incidence of esophageal cancer is higher in alcoholics.', 'Rat esophageal samples were incubated with all-trans retinal and newly formed all-trans retinoic acid (ATRA) was quantified using high-performance liquid chromatography (HPLC). Furthermore, beta-nicotinamide adenine dinucleotide (NAD)-dependent acetaldehyde oxidation by the rat esophagus was examined by tracing NAD reduction using a spectrophotometer.', 'Rat esophageal samples produced ATRA from all-trans retinal in a NAD-dependent manner and the potential was significantly attenuated by phenetyl isothiocynate, an ALDH inhibitor, or acetaldehyde depending on the concentration used. Rat esophageal samples also oxidized acetaldehyde of various concentrations NAD dependently. The ATRA formation potential that was temporarily inhibited by acetaldehyde was recovered to the control level by dialysis when the specimen was incubated with up to 50 microM of acetaldehyde.",
            "output": [
                "Does acetaldehyde inhibit the formation of retinoic acid from retinal in the rat esophagus?"
            ]
        },
        {
            "id": "task847-385f9dbec5324cef93b2a486adf1c8c1",
            "input": "Despite the clinical efficacy of recombinant human erythropoietin (RHE) on chemotherapy-induced anemia, most cost-effectiveness studies have given unfavorable results.', 'To determine the cost of managing anemia in unselected patients receiving chemotherapy for lung cancer, and the efficacy and cost-effectiveness of RHE.', 'We constructed Markov models of two cohorts of patients who received (n=94) or did not receive (n=89) darbepoetin (one weekly injection when the hemoglobin level fell below 11 g/dl), focusing on changes in hemoglobin levels, transfusion requirements, anemia management costs, and the cost-effectiveness ratios of the two management strategies.', 'The use of RHE significantly reduced the proportion of patients needing transfusions (from 33.6% to 19.1%, p<0.05) and the number of red cell units used by transfusion (from 2.97+/-1.47 to 2.11+/-0.47, p<0.01). Markov modeling showed that the RHE strategy significantly increased the mean Hb level (13+/-0.5 g/dl versus 11.9+/-1g/dl, p<0.001), at the price of an increase in the main cost (respectively, US$ 1732+/-897 and 996+/-643; p<0.01). The cost-effectiveness ratio favored the RHE strategy (7.02 versus 9.04). Sensitivity analysis showed that the RHE strategy remained dominant in most situations.",
            "output": [
                "Is routine once-weekly darbepoetin alfa administration cost-effective in lung cancer patients with chemotherapy-induced anemia : a Markov analysis?"
            ]
        },
        {
            "id": "task847-cd7577adfa5b45b69ef8a1616a8c0760",
            "input": "In the present study, the passive resistance of the human jaw system was quantified in relation to the three-dimensional jaw displacement and the Posselt-envelope, using both in vivo measurements and computer simulation.', 'In eight subjects, the jaw was passively displaced with a step-wise increasing force in three orthogonal directions. Muscle relaxation was monitored using electromyography (EMG) with visual feedback. A biomechanical model of an average human system was used to examine the contributions of the jaw muscles.', \"The largest excursion was found for the vertical direction. Protrusive and lateral directions were more restricted. In protrusive and lateral directions, the jaw could generally move beyond the Posselt-envelope. The stiffness of the jaw increased with proceeding jaw displacement in all directions. The stiffness was larger in the protrusive direction than in the vertical and lateral directions. The model's predictions of stiffness were comparable to the in vivo measurements. However, in protrusive direction, the maximum jaw displacement was larger than in vivo. The estimated passive muscle forces showed that vertical displacement was mainly restricted by the complete group of closing muscles, while protrusive and lateral jaw displacement was restricted by selective individual muscles.",
            "output": [
                "Does passive resistance increase differentially in various jaw displacement directions?"
            ]
        },
        {
            "id": "task847-2b257e5dba1743d3a0a541d0cf6b8678",
            "input": "We evaluate the frequency of empiric acyclovir administration to patients in the emergency department (ED) who are ultimately diagnosed with encephalitis.', \"We conducted an explicit retrospective medical record review of consecutive patients discharged with a final diagnosis of herpes simplex encephalitis or viral encephalitis not otherwise specified for the period 1993 to 2003. The frequency of ED administration of empiric acyclovir was measured for patients who met the inclusion criteria of fever, neuropsychiatric abnormality, and cerebrospinal fluid pleocytosis with a negative Gram's stain result in the ED.\", \"Of the 90 patients reviewed, 24 (27%) met the inclusion criteria of fever, neuropsychiatric abnormality, and cerebrospinal fluid pleocytosis with a negative Gram's stain result in the ED. Of these 24 patients, 7 (29%) received empiric acyclovir in the ED, 6 (86%) patients after cerebrospinal fluid results were available, with a median time to administration of 1.5 hours (95% confidence interval [CI] 0 to 3.1 hours). The remaining 17 (71%) patients did not receive acyclovir in the ED, with median times of 16 hours (95% CI 7.5 to 44 hours) before initiation of acyclovir in inpatient settings.",
            "output": [
                "Is empiric acyclovir infrequently initiated in the emergency department to patients ultimately diagnosed with encephalitis?"
            ]
        },
        {
            "id": "task847-e354f1d6c0ee408b98b41b7f6133ae1e",
            "input": "To evaluate the mechanism of oxidative stress at glucose levels accompanying diabetic pregnancy. Specifically, we hypothesize that elevated glucose overwhelms hexose monophosphate shunt (HMS) down-regulation observed during pregnancy.', 'Peripheral blood cells from normal healthy pregnant women were exposed to heightened glucose levels to provide an in vitro model of the effects of diabetic pregnancy. Changes in NAD(P)H, reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated in single cells.', 'Altered metabolic dynamics, as judged by NAD(P)H autofluorescence of neutrophils from both pregnant and non-pregnant women, were observed during incubation with 14 mM glucose, a pathophysiologic level. In parallel, increased production of ROS and NO was observed. The ROS and NO levels attained in cells from pregnant women were greater than those observed in cells from non-pregnant women. Inhibitors of the HMS and NAD(P)H oxidase blocked these effects. These metabolic and oxidant changes required approximately one minute, suggesting that transient glucose spikes during pregnancy could trigger this response.",
            "output": [
                "Is oxidant release dramatically increased by elevated glucose concentrations in neutrophils from pregnant women?"
            ]
        },
        {
            "id": "task847-40477266948e492097b47d18f10b65e3",
            "input": "Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk of coronary heart disease by 11% to 16% and stroke by 19% to 24%. Individuals homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism have reduced MTHFR enzyme activity resulting from the inappropriate loss of the riboflavin cofactor, but it is unknown whether their typically high homocysteine levels are responsive to improved riboflavin status.', 'From a register of 680 healthy adults 18 to 65 years of age of known MTHFR 677C-->T genotype, we identified 35 with the homozygous (TT) genotype and age-matched individuals with heterozygous (CT, n=26) or wild-type (CC, n=28) genotypes to participate in an intervention in which participants were randomized by genotype group to receive 1.6 mg/d riboflavin or placebo for a 12-week period. Supplementation increased riboflavin status to the same extent in all genotype groups (8% to 12% response in erythrocyte glutathione reductase activation coefficient; P<0.01 in each case). However, homocysteine responded only in the TT group, with levels decreasing by as much as 22% overall (from 16.1+/-1.5 to 12.5+/-0.8 micromol/L; P=0.003; n=32) and markedly so (by 40%) in those with lower riboflavin status at baseline (from 22.0+/-2.9 and 13.2+/-1.0 micromol/L; P=0.010; n=16). No homocysteine response was observed in the CC or CT groups despite being preselected for suboptimal riboflavin status.",
            "output": [
                "Does riboflavin lower homocysteine in individuals homozygous for the MTHFR 677C- > T polymorphism?"
            ]
        },
        {
            "id": "task847-5ff4e30611f14ed49d18f1b07e4422a8",
            "input": "Cyclooxygenase-1 (COX-1) has been implicated in the pathogenesis of atherothrombosis and is expressed by the major cell types of atherosclerotic lesions. COX-1-mediated platelet thromboxane (TX) production has been proposed to promote both early atherosclerosis and thrombosis. Here, we examined the impact of COX-1 deficiency in bone marrow-derived cells on early atherogenesis in the mouse.', 'LDL receptor (LDLR)(-/-) and apolipoprotein E (apoE)(-/-) recipient mice were lethally irradiated and transplanted with COX-1(-/-) bone marrow. Mice reconstituted with COX-1(-/-) marrow had nearly complete (99.7%) loss of platelet TXA2 and significantly suppressed levels of macrophage and urinary TXA2 metabolites. Serum lipid levels and lipoprotein distributions did not differ between recipients reconstituted with COX-1(+/+) and COX-1(-/-) marrow. Surprisingly, the extent of atherosclerotic lesions in both LDLR(-/-) and apoE(-/-) mice reconstituted with COX-1(-/-) marrow was increased significantly compared with control mice transplanted with COX-1(+/+) marrow. Peritoneal macrophages isolated from LDLR(-/-) mice reconstituted with COX-1(-/-) marrow had increased lipopolysaccharide-induced levels of COX-2 mRNA and protein expression. Fetal liver cell transplantation studies revealed a 30% increase in atherosclerosis in COX-1(-/-)-->LDLR(-/-)mice compared with COX-1(+/+)-->LDLR(-/-)mice, whereas the extent of atherosclerosis was unchanged in COX-1(-/-)/COX-2(-/-)-->LDLR(-/-)mice.",
            "output": [
                "Does cyclooxygenase-1 deficiency in bone marrow cells increase early atherosclerosis in apolipoprotein E- and low-density lipoprotein receptor-null mice?"
            ]
        },
        {
            "id": "task847-ebcf79db3cd1429c892eb84a4ff65933",
            "input": "A number of distinct stress signaling pathways in myocardium cause cardiac hypertrophy and heart failure. Class II histone deacetylases (HDACs) antagonize several stress-induced pathways and hypertrophy. However, cardiac hypertrophy induced by transgenic overexpression of the homeodomain only protein, HOP, can be prevented by the nonspecific HDAC inhibitors trichostatin A and valproic acid, suggesting that alternate targets that oppose class II HDAC function might exist in myocardium. We tested the effects of several HDAC inhibitors, including a class I HDAC-selective inhibitor, SK-7041, on cardiac hypertrophy induced by angiotensin II (Ang II) treatment or aortic banding (AB).', 'Cardiac hypertrophy was induced by chronic infusion of Ang II or by AB in mice or rats and evaluated by determining the ratio of heart weight to body weight or to tibia length, cross-sectional area, or echocardiogram. Cardiac hypertrophy induced by Ang II or AB for 2 weeks was significantly reduced by simultaneous administration of trichostatin A, valproic acid, or SK-7041. Echocardiogram revealed that exaggerated left ventricular systolic dimensions were relieved by HDAC inhibitors. HDAC inhibitors partially reversed preestablished cardiac hypertrophy and improved survival of AB mice. The expressions of atrial natriuretic factor, alpha-tubulin, beta-myosin heavy chain, and interstitial fibrosis were reduced by HDAC inhibition.",
            "output": [
                "Does inhibition of histone deacetylation block cardiac hypertrophy induced by angiotensin II infusion and aortic banding?"
            ]
        },
        {
            "id": "task847-0eba883a68494157bab70bcfd3ffeea9",
            "input": "Diacylglycerol is a lipid second messenger that accumulates in cardiomyocytes when stimulated by Gqalpha protein-coupled receptor (GPCR) agonists such as angiotensin II, phenylephrine, and others. Diacylglycerol functions as a potent activator of protein kinase C (PKC) and is catalyzed by diacylglycerol kinase (DGK) to form phosphatidic acid and inactivated. However, the functional roles of DGK have not been previously examined in the heart. We hypothesized that DGK might prevent GPCR agonist-induced activation of diacylglycerol downstream signaling cascades and subsequent cardiac hypertrophy.', 'To test this hypothesis, we generated transgenic (DGKzeta-TG) mice with cardiac-specific overexpression of DGKzeta. There were no differences in heart size and heart weight between DGKzeta-TG and wild-type littermate mice. The left ventricular function was normal in DGKzeta-TG mice. Continuous administration of subpressor doses of angiotensin II and phenylephrine caused PKC translocation, gene induction of atrial natriuretic factor, and subsequent cardiac hypertrophy in WT mice. However, in DGKzeta-TG mice, neither translocation of PKC nor upregulation of atrial natriuretic factor gene expression was observed after angiotensin II and phenylephrine infusion. Furthermore, in DGKzeta-TG mice, angiotensin II and phenylephrine failed to increase cross-sectional cardiomyocyte areas and heart to body weight ratios. Phenylephrine-induced increases in myocardial diacylglycerol levels were completely blocked in DGKzeta-TG mouse hearts, suggesting that DGKzeta regulated PKC activity by controlling cellular diacylglycerol levels.",
            "output": [
                "Does cardiac-specific overexpression of diacylglycerol kinase zeta prevent Gq protein-coupled receptor agonist-induced cardiac hypertrophy in transgenic mice?"
            ]
        },
        {
            "id": "task847-57c8626963774e029e6e6fe9e90df7f1",
            "input": "Diastolic dysfunction, manifested by impaired left ventricular (LV) relaxation, is prevalent among individuals with metabolic disorders. The objective of this study was to evaluate the extent to which plasma triglyceride (TG) levels are related to LV diastolic function.', 'A total of 424 subjects (age 49 +/- 12 years) had fasting plasma TG levels measured and underwent echocardiography for assessment of LV structure and function: LV ejection fraction and LV mass indexed to height (LVM/Ht(2.7)); transmitral inflow early diastolic peak velocity (E wave) and late diastolic peak velocity (A wave), and E wave to A wave ratio (E/A); deceleration time; and Doppler tissue imaging early diastolic myocardial velocity (EM), an index of LV relaxation.', 'All subjects had normal LV ejection fraction, 48% had hypertension, 16% had increased LVM/Ht(2.7), 11% had type 2 diabetes mellitus, 37% were obese, and 27% had hypertriglyceridemia (TG > 150 mg/dL). Univariate analysis showed significant relationships between TG level and E/A, deceleration time, and Em (P < or = .001 for all). After adjustment for potential confounders in multivariate models (eg, age, systolic blood pressure, and LVM/Ht(2.7)), TG levels remained predictive of E/A, deceleration time, and Em (P < or = .05, <.001, and < or =.0001, respectively). Stepwise multivariate analysis showed that after age and body mass index, the TG level was the next most predictive variable of Em.",
            "output": [
                "Is plasma triglyceride level an independent predictor of altered left ventricular relaxation?"
            ]
        },
        {
            "id": "task847-22cfc7a59c97432484124450fef521b5",
            "input": "We continue statistical development of the posterior probability of linkage (PPL). We present a two-point PPL allowing for unequal male and female recombination fractions, thetaM and thetaF, and consider alternative priors on thetaM, thetaF.', 'We compare the sex-averaged PPL (PPLSA), assuming thetaM = thetaF, to the sex-specific PPL (PPLSS) in (thetaM, thetaF), in a series of simulations; we also compute the PPLSS using alternative priors on (thetaM, thetaF).', 'The PPLSS based on a prior that ignores prior genomic information on sex specific recombination rates performs essentially identically to the PPLSA, even in the presence of large thetaM, thetaF differences. Moreover, adaptively skewing the prior, to incorporate (correct) genomic information on thetaM, thetaF differences, actually worsens performance of the PPLSS. We demonstrate that this has little to do with the PPLSS per se, but is rather due to extremely high levels of variability in the location of the maximum likelihood estimates of (thetaM, thetaF) in realistic data sets.",
            "output": [
                "Does the incorporation of prior genomic information necessarily improve the performance of Bayesian linkage methods : an example involving sex-specific recombination and the two-point PPL?"
            ]
        },
        {
            "id": "task847-1185f35b9e8a44f2918d7c87b5b9853a",
            "input": "Mutations of the caspase-activating recruitment domain 15 (CARD15) gene on chromosome 16 are associated with chronic inflammatory granulomatous bowel disease (Crohn's disease). Sarcoidosis is a systemic granulomatous disease with unknown etiology, which shares histological features with Crohn's disease.\", 'To evaluate whether ethnic Danes with sarcoidosis have an increased frequency of CARD15 mutations compared to healthy control subjects.', 'Genotyping for CARD15 mutations R702W, G908R, and L1007fsinsC, also designated single nucleotide polymorphism (SNP) SNP8, SNP12 and SNP13, respectively, were performed by capillary electrophoresis single-strand confirmation polymorphism in 53 patients with histologically verified sarcoidosis and in 103 healthy controls.', 'The frequencies of CARD15 mutations in sarcoidosis patients were: SNP8, 4/106 chromosomes (3.8%); SNP12, 2/106 chromosomes (1.9%); SNP13, 2/106 chromosomes (1.9%); SNP8+SNP12+SNP13, 8/106 chromosomes (7.6%). All 8 patients were heterozygous. The frequencies in controls were: SNP8, 9/206 chromosomes (4.4%); SNP12, 2/206 chromosomes (1.0%); SNP13, 4/206 chromosomes (1.9%); SNP8+SNP12+SNP13, 15/206 chromosomes (7.3%). All controls were heterozygous. The differences were not statistically significant (p>0.05). Furthermore, the course of disease was not significantly different in the 8 patients with CARD15 mutations and the 45 patients without mutations.",
            "output": [
                "Are cARD15 single nucleotide polymorphisms 8 , 12 and 13 increased in ethnic Danes with sarcoidosis?"
            ]
        },
        {
            "id": "task847-9930253f34e648cca0849768d3ba2d56",
            "input": "Human interleukin 10 (hIL-10) may reduce acute rejection after organ transplantation. Our previous data shows that electroporation-mediated transfer of plasmid DNA to peripheral muscle enhances gene transduction dramatically. This study was designed to investigate the effect of electroporation-mediated overexpression of hIL-10 on acute rejection of cardiac allografts in the rat.', 'The study was designed to evaluate the effect of hIL-10 gene transfer on (a) early rejection pattern and (b) graft survival. Gene transfer was achieved by intramuscular (i.m.) injection into the tibialis anterior muscle of Fischer (F344) male recipients followed by electroporation 24 h prior to transplantation. Heterotopic cardiac transplantation was performed from male Brown Norway rat to F344. Four groups were studied (n = 6). Treated animals in groups B1 and B2 received 2.5 microg of pCIK hIL-10 and control animals in groups A1 and A2 distilled water. Graft function was assessed by daily palpation. Animals from group A1 were sacrificed at the cessation of the heart beat of the graft and those in group B1 were sacrificed at day 7; blood was taken for ELISA measurement of hIL-10 and tissue for myeloperoxidase (MPO) measurement and histological assessment. To evaluate graft survival, groups A2 and B2 were sacrificed at cessation of the heart beat of the graft.', 'Histological examination revealed severe rejection (IIIB-IV) in group A1 in contrast to low to moderate rejection (IA-IIIA) in group B1 (p = 0.02). MPO activity was significantly lower in group B1 compared to group A1 (18 +/- 7 vs. 32 +/- 14 mU/mg protein, p = 0.05). Serum hIL-10 levels were 46 +/- 13 pg/ml in group B1 vs. 0 pg/ml in group A1. At day 7 all heart allografts in the treated groups B1 and B2 were beating, whereas they stopped beating at 5 +/- 2 days in groups A1 and A2 vs. 14 +/- 2 days in group B2 (p = 0.0012).",
            "output": [
                "Does electroporation-mediated interleukin-10 overexpression in skeletal muscle reduce acute rejection in rat cardiac allografts?"
            ]
        },
        {
            "id": "task847-c56f0cc21f9b439b9ca8f9baf2c319bf",
            "input": "Therapeutic and prophylactic vena cava filters (VCFs) are used to prevent pulmonary embolism. Concerns exist over placing a permanent filter in a young trauma patient. Recently, retrievable VCFs have become available. One such filter is the OptEase, which has a recommended time of removal of up to 23 days after insertion. Data supporting this recommendation are sparse. Many trauma patients will need filters for more than 2 weeks, and there are no data evaluating the safety of removal after extended time periods. The purpose of this study was to determine the safety, feasibility, and reaction of the vena cava when removing the OptEase retrievable VCF at different time intervals.', 'Twenty Yorkshire cross pigs (80-113 kg) underwent general anesthesia with tiletamine and zolazepam. Filters were placed in the infrarenal vena cava (VC) through the femoral vein under fluoroscopic guidance. Animals were then divided into four groups. In group 1, filters were removed at 14 days; in group 2, at 30 days; in group 3, at 60 days; and in group 4, at 90 days. Removal was attempted using a snare-and-sheath technique through the femoral vein. Animals with successful filter removal were allowed to recover; then, the animals underwent autopsy (gross and microscopic VC examination) 2 months later. Animals with unsuccessful filter removal underwent autopsy immediately after attempted removal. Venacavograms were taken at filter insertion, at removal, and before autopsy to evaluate any VC abnormalities.', 'Successful removal of the filter in all five pigs (100%) was reliably performed only in the 14-day group. In this group, the initial VC transverse diameter was 19.4 +/- 0.8 mm and was significantly reduced to 9.8 +/- 1.1 mm (p < 0.05) immediately after removal. Sixty days later, before autopsy, VC diameter had increased to 15.3 +/- 1.9 mm, which was significantly larger than at removal (p < 0.05) but not different from the initial value. In the 30-day group, removal was successful in only one of five animals. Although removal was successful in the one pig, autopsy at 2 months postremoval revealed total occlusion of the VC. Filters could not be removed from 60- and 90-day groups. At autopsy, the VCF struts were embedded or protruded through the VC wall. Microscopic examination of the VC revealed significant scarring underneath and between the struts.",
            "output": [
                "Is removal of the OptEase retrievable vena cava filter feasible after extended time periods because of filter protrusion through the vena cava?"
            ]
        },
        {
            "id": "task847-d2dd66f2904e4670b24807c0227ccc10",
            "input": "Chronic kidney disease (CKD) is associated with increased cardiovascular events. The relationships between the markers of inflammation and endothelial dysfunction were investigated both before and after living donor kidney transplantation.', 'Twenty-seven renal transplant patients were studied. Eleven patients (six male, five female) were on cyclosporine A, whereas 16 patients (nine male, seven female) were treated with tacrolimus based regimes. Twenty-seven subjects (12 males, 15 females) were studied as controls. Plasma adiponectin, high sensitive C reactive protein (hsCRP), Asymetric dimethyl arginine (ADMA) levels were studied before transplantation and on days 1, 3, 7, 14, and 28. The brachial artery flow mediated dilatation (FMD) was studied before transplantation and on the 28th day.', 'Serum hsCRP and ADMA levels decreased significantly from the first posttransplantation day on each measurement (P<0.001 for all) while the decrement of plasma adiponectin started in the third day (P<0.001 for all). The FMD was lower in the patients than the control group (P<0.001) and improved significantly in the 28th day of transplantation (P<0.001).",
            "output": [
                "Do endothelial functions improve with decrease in asymmetric dimethylarginine ( ADMA ) levels after renal transplantation?"
            ]
        },
        {
            "id": "task847-55d26cbdc22c494d873b7d7a1f11f09e",
            "input": "Flow cytometry (FACS) is a common technique in blood banking. It is used, for example, for the enumeration of residual white blood cells in plasma and in cellular blood products. It was investigated whether it can also be applied for sterility testing of buffy coat-derived platelet concentrates (PCs).', 'Plasma-reduced PCs were spiked with bacteria and stored at 20 to 24 or 37 degrees C for various times. The following 10 species were used: Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Propionibacterium acnes, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, and Yersinia enterocolitica. Bacterial DNA was stained with thiazole orange. After the platelets were lysed, bacteria were enumerated by FACS.', 'All bacteria species used were detectable by FACS. The lower detection limit was approximately 100 bacteria per microL, that is, 10(5) per mL. In general, the titers measured were 1.2- to 3-fold higher than those determined by colony forming assay. In one case (K. pneumoniae) in which the dot plot of the bacteria cloud overlapped with that of bacteria debris, they were consistently lower. When PC samples were inoculated with approximately 1 colony-forming unit per mL of bacteria and kept at 37 degrees C, most species were detected within 21 hours or less. Exceptions were E. cloacae and P. acnes, which were detected after 24 to 40 and 64 hours, respectively. At 20 to 24 degrees C, the detection times were strongly prolonged.",
            "output": [
                "Does basics of flow cytometry-based sterility testing of platelet concentrate?"
            ]
        },
        {
            "id": "task847-278d46783d604542a2aee3e62713dc73",
            "input": "Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. MATWERIALS AND METHODS: We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N -monomethyl-L-arginine (NMMA), lipids and body composition were measured.', 'Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75x in obese men and by 1.27x in elderly men. Postabsorptive ADMA (r=0.71), SDMA (r=0.46), and NMMA (r=0.31) correlated (all p<0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake (p<0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates (p<0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides (p<0.05).",
            "output": [
                "Are elevations of plasma methylarginines in obesity and ageing related to insulin sensitivity and rates of protein turnover?"
            ]
        },
        {
            "id": "task847-df08083380254cddbe91f9fa4ba3065d",
            "input": "Cytotechnologists and pathologists often perform onsite evaluations of thyroid fine-needle aspirations (FNAs) to provide immediate feedback regarding whether adequate material has been obtained for cytologic diagnosis. The current study was designed to determine whether onsite adequacy assessment results in a significant decrease in nondiagnostic specimens between ultrasound (US)-guided FNAs of the thyroid and those performed by palpation alone.', 'A search was performed to identify in-house thyroid FNAs performed between January 1, 2000 and December 31, 2003 that were obtained under US guidance or by palpation only. It was then recorded whether an onsite adequacy assessment was performed. The submitting physician and final diagnosis also were recorded for each case. Contingency tables were constructed and evaluated using chi-square analysis.', 'Of 1502 in-house thyroid FNAs included in the current study, 981 (65.3%) were performed under US guidance and 521 (34.7%) were performed with palpation alone. Onsite adequacy assessment of the aspirated material was performed in 323 cases (21.5%), whereas 1179 cases (78.5%) were performed without onsite evaluation. Of the 418 palpation-guided FNAs that were performed without adequacy assessment, 70 (16.7%) were reported to be nondiagnostic, whereas of the 103 palpation-guided FNAs with immediate evaluation, only 7 (6.8%) were determined to be inadequate for diagnosis. This difference was statistically significant (P < 0.025). Of 761 US-guided FNAs without immediate adequacy assessment, 54 (7.1%) were nondiagnostic, which was not statistically different from the nondiagnostic rate of 4.5% (10 of 220 cases) for US-guided FNAs with onsite evaluation. However, when these US-guided FNAs were divided further into 2 groups based on the experience of the radiologist performing the FNA, the nondiagnostic rate in the group of experienced radiologists was only 5.4% (or 32 of 592 US-guided FNAs), even though onsite evaluation was not performed. Among radiologists with less experience, adequacy assessment significantly reduced the nondiagnostic rate from 13.0% (22 of 169 FNAs without adequacy assessment) to 4.5% (10 of 220 FNAs with adequacy assessment) (P < 0.01).",
            "output": [
                "Is the value of onsite adequacy assessment of thyroid fine-needle aspirations a function of operator experience?"
            ]
        },
        {
            "id": "task847-f8f17a6214d245c5a8b5aa51ffe770d4",
            "input": "Migraine is associated with epilepsy, but the time order and nature of the relationship are unclear. We conducted a population based case control study to clarify the time order to determine whether migraine is a risk factor for epilepsy.', 'Migraine symptoms were evaluated in a population-based case-control study of all incident epilepsy in Icelandic children and in matched controls (next two same sex births in the country).', 'Migraine was associated with a fourfold increased risk for developing epilepsy, an association explained by migraine with aura (odds ratio, 8.1; 95% confidence interval, 2.7-24.3). Migraine without aura did not increase risk for epilepsy.",
            "output": [
                "Is migraine with aura a risk factor for unprovoked seizures in children?"
            ]
        },
        {
            "id": "task847-e92f462c94b9455c898b73c0fb4d5800",
            "input": "Parkinsonian signs, especially gait impairment, are common and associated with morbidity and mortality in older persons. Our objective was to test the hypothesis that substantia nigra neurofibrillary tangles (NFTs) are related to parkinsonian signs in older persons with and without dementia.', \"We studied 86 deceased older Catholic clergy without idiopathic Parkinson's disease from the Religious Order Study, a longitudinal clinical-pathological study. Mean age at death was 85.3 years. Signs of gait disturbance, bradykinesia, rigidity, and tremor were assessed proximate to death using a modified Unified Parkinson's Disease Rating Scale. Forty-micrometer paraffin-embedded sections of substantia nigra were bleached before tau immunohistochemistry and the optical disector was used to count NFTs. We used multivariable linear regression to examine parkinsonian signs as a function of nigra NFTs, controlling for age, sex, education, and cortical NFTs.\", 'Substantia nigra NFTs were present in 67 of 86 persons (77.9%). After controlling for age, sex, education, and cortical NFTs, nigra NFTs were related to gait impairment (p < 0.001), but not bradykinesia, rigidity, or tremor. Results were not confounded by dementia, Braak score, neuroleptic medication, cerebral infarcts, or Lewy bodies.",
            "output": [
                "Are substantia nigra tangles related to gait impairment in older persons?"
            ]
        },
        {
            "id": "task847-a5d670200f8a49c6949190b58b99d412",
            "input": "The objectives were to analyze the cardiac effects of exposure to tobacco smoke (ETS), for a period of 30 days, alone and in combination with beta-carotene supplementation (BC).', 'Rats were allocated into: Air (control, n = 13); Air + BC (n = 11); ETS (n = 11); and BC + ETS (n = 9). In Air + BC and BC + ETS, 500 mg of BC were added to the diet. After three months of randomization, cardiac structure and function were assessed by echocardiogram. After that, animals were euthanized and morphological data were analyzed post-mortem. One-way and two-way ANOVA were used to assess the effects of ETS, BC and the interaction between ETS and BC on the variables.', 'ETS presented smaller cardiac output (0.087 +/- 0.001 vs. 0.105 +/- 0.004 l/min; p = 0.007), higher left ventricular diastolic diameter (19.6 +/- 0.5 vs. 18.0 +/- 0.5 mm/kg; p = 0.024), higher left ventricular (2.02 +/- 0.05 vs. 1.70 +/- 0.03 g/kg; p < 0.001) and atrium (0.24 +/- 0.01 vs. 0.19 +/- 0.01 g/kg; p = 0.003) weight, adjusted to body weight of animals, and higher values of hepatic lipid hydroperoxide (5.32 +/- 0.1 vs. 4.84 +/- 0.1 nmol/g tissue; p = 0.031) than Air. However, considering those variables, there were no differences between Air and BC + ETS (0.099 +/- 0.004 l/min; 19.0 +/- 0.5 mm/kg; 1.83 +/- 0.04 g/kg; 0.19 +/- 0.01 g/kg; 4.88 +/- 0.1 nmol/g tissue, respectively; p > 0.05). Ultrastructural alterations were found in ETS: disorganization or loss of myofilaments, plasmatic membrane infolding, sarcoplasm reticulum dilatation, polymorphic mitochondria with swelling and decreased cristae. In BC + ETS, most fibers showed normal morphological aspects.",
            "output": [
                "Does beta-carotene supplementation attenuate cardiac remodeling induced by one-month tobacco-smoke exposure in rats?"
            ]
        },
        {
            "id": "task847-503d1116c28a4576b5d8b5463497f997",
            "input": "The objective in lung transplantation is to prolong life, but the survival effect in patients with chronic obstructive pulmonary disease (COPD) or alpha1-anti-trypsin deficiency emphysema is still unresolved. This study assesses the impact of diagnosis, single-lung transplantation (SLT) vs bilateral lung transplantation (BLT) and timing of transplantation on survival in a national cohort.', 'In 219 consecutive patients accepted onto the lung transplantation waiting list in Norway, 1990 to 2003, we assessed predictors of death: (1) on the waiting list; (2) <or=90 days after transplantation; and (3) >90 days after transplantation. For each period we used Cox regression, including age, gender, diagnosis, baseline pulmonary function tests, cardiac catheterization data, exercise capacity and transplant type, as potential predictors. Survival benefit was assessed graphically by combining adjusted survival curves after transplantation with the curve for those waiting, modeling transplantation after 6, 12 or 24 months.', 'Mean patient age was 49 years (SD 10), with 55% women. High forced expiratory volume in 1 second (FEV(1)) percentage predicted death on the waiting list. Diagnoses other than COPD/emphysema and receiving SLT were associated with death <or=90 days after transplantation. Only low forced vital capacity (FVC) percentage predicted death >90 days after transplantation. In COPD/emphysema, there was no clear survival benefit from BLT or SLT. For patients in the \"Other\" group, the data suggest a survival benefit from BLT.",
            "output": [
                "Is lung transplantation in patients with chronic obstructive pulmonary disease in a national cohort without obvious survival benefit?"
            ]
        },
        {
            "id": "task847-8980dccc3c354c50bf3453139a0ae9b9",
            "input": "Lung transplantation is severely limited by an inadequate supply of lungs from brain-dead donors. A potential solution is use of lungs from non-heart-beating donors (NHBDs) with retrieval at intervals after circulatory arrest and death. A warm ischemic period with concomitant reperfusion injury is a major limiting factor in the transplantation of lungs retrieved from NHBDs. We hypothesized that the administration of the nitric oxide-donor nitroglycerin to lungs from NHBDs would reduce ischemia-reperfusion injury by activation of guanylate cyclase to form guanosine 3',5'-cyclic monophosphate (cGMP).\", \"An in situ isolated perfused rat lung model was used. Lungs were retrieved from rats at varying intervals after circulatory arrest and death. Lungs were either ventilated with O(2) in situ or not ventilated. Lungs were reperfused at intervals after death with Earle's solution with or without nitroglycerin (0.1 mg/ml). Lung ischemia-reperfusion injury was assessed by capillary filtration coefficient, wet-to-dry lung weight ratio, and pulmonary hemodynamics. Tissue levels of adenine nucleotides and cGMP concentrations were measured by high-performance liquid chromatography and enzyme immunoassay, respectively.\", 'Reperfusion with nitroglycerin decreased capillary filtration coefficient compared with reperfusion without nitroglycerin at all post-mortem ischemic times, irrespective of pre-harvest ventilation. cGMP levels increased significantly with nitroglycerin-reperfusion and attenuated decreases in high-energy adenine nucleotides.",
            "output": [
                "Does nitroglycerin reperfusion reduce ischemia-reperfusion injury in non-heart-beating donor lungs?"
            ]
        },
        {
            "id": "task847-c319c70ac06b4c058c4c67c66a5771b8",
            "input": "The aim of this study was to determine whether absorption and spirituality predict the placebo response independently of expectancy.', \"This was an open study of self-treatment with self-selected Bach flower essences. Participants' expectancy of the effect of flower essences, attitudes to complementary medicine, holistic health beliefs, absorption, and spirituality were measured prior to treatment. One month after the start of treatment, participants responded to an e-mail enquiry about symptom change using a single seven-point change scale.\", 'One hundred sixteen participants (97 university undergraduates and 19 staff) completed all assessments. Spirituality and absorption together predicted additional variance compared with a cluster of expectancy measures comprising expectancy, attitude to complementary medicine, and holistic beliefs (increment in R(2)=.042, P=.032), and spirituality alone (but not absorption alone) predicted more additional variance than did the expectancy cluster (increment in R(2)=.043, P=.014).",
            "output": [
                "Does spirituality predict outcome independently of expectancy following flower essence self-treatment?"
            ]
        },
        {
            "id": "task847-6d2cd896c57d4f9eaae6cad78a5db693",
            "input": "To assess the effectiveness of the combined use of fecal calprotectin (FC), anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear staining antineutrophil antibody (pANCA), small intestinal permeability test (IP), and bowel wall ultrasonography measurement (BWUS) in the diagnostic work-up of children with suspected inflammatory bowel disease (IBD).', 'All children referred for initial assessment of possible IBD were eligible. Patients with symptoms or signs (right-lower quadrant mass, perianal disease, or hematochezia) mandating a complete work-up for IBD were excluded. All enrolled patients underwent a clinical, laboratory, radiographic, and endoscopic evaluation including biopsy examinations. The immunoglobulin (Ig)G and IgA ASCA, IgG pANCA, FC, IP, and BWUS were tested in all patients at the initial assessment.', 'A final diagnosis of IBD was made in 27 patients: 17 Crohn disease and 10 ulcerative colitis. Eighteen children had other gastrointestinal diagnoses (8 functional bowel disorders, 5 food allergy-mediated diseases, 4 infectious enterocolitis, 1 familial Mediterranean fever). In patients with simultaneous abnormal values of FC, BWUS, and ASCA/pANCA, the estimated probability of having IBD was 99.47%. Patients with negative results on all tests had a 0.69% of probability of IBD.",
            "output": [
                "Is combined use of noninvasive tests useful in the initial diagnostic approach to a child with suspected inflammatory bowel disease?"
            ]
        },
        {
            "id": "task847-754c33ba4ade42eb8d25b4230e358fa4",
            "input": "Coronary artery bypass grafting has been performed for a long period utilizing saphenous vein grafts, the fate of which might be crucial to prognosis following the operation. Metabolic syndrome, on the other hand, has become an increasingly important part of cardiovascular practice. We examined whether there was any negative effect of metabolic syndrome on saphenous vein graft patency in a relatively short term (< or =5 years).', 'Coronary angiograms of 314 consecutive patients (mean age 62.6+/-8.5 years), having at least one saphenous vein bypass graft within the last 5 years, were evaluated.', 'One hundred and twenty-one patients (group 1) had either an occluded saphenous vein graft or a saphenous vein graft with a significant lesion, and 193 patients (group 2) had patent saphenous vein grafts. Metabolic syndrome was present in 46.2% of all patients (n=145), in 57% of patients in group 1 and in 39.4% of patients in group 2 (P=0.002). Having metabolic syndrome increased the risk of saphenous vein graft occlusion or having a significant lesion on saphenous vein grafts by 2.04-folds. In multivariable logistic regression, smoking (P=0.015, odds ratio=1.88), metabolic syndrome (P=0.019, odds ratio=1.81) and diabetes mellitus (P=0.048, odds ratio=1.36) were found to be associated with poor venous graft fate in the relatively short-term period after bypass.",
            "output": [
                "Does metabolic syndrome negatively impact early patency of saphenous vein grafts?"
            ]
        },
        {
            "id": "task847-3596fb8cd56a4857b823b68cd2ab2a29",
            "input": "Prognosis of severe coronary artery disease with no indication of percutaneous coronary intervention or coronary artery bypass grafting remains poor. We have recently demonstrated that shock wave therapy effectively induces neovascularization and improves myocardial ischemia in a porcine model in vivo.', 'With permission from the Ethical Committee of our Institute, we treated nine patients with end-stage coronary artery disease with no indication of percutaneous coronary intervention or coronary artery bypass grafting (55-82 years old, five men and four women) with our cardiac shock wave therapy (200 shots/spot at 0.09 mJ/mm for 20-40 spots, 3 times a week/series). We followed-up the patients at 1, 3, 6, and 12 months after the therapy to examine the amelioration of myocardial ischemia. When needed, shock wave therapy was performed up to three series at 0, and 1, 3 or 6 months.', 'The cardiac shock wave therapy improved symptoms (Canadian Cardiovascular Society functional class score, from 2.7+/-0.2 to 1.8+/-0.2, P<0.01) and reduced nitroglycerin use (from 5.4+/-2.5 to 0.3+/-0.3/week, P<0.05). The treatment also improved myocardial perfusion as assessed by dipyridamole stress thallium scintigraphy (severity score, 25.2+/-7.2% improvement, P<0.05; extent score, 23.3+/-9.0% improvement, P=0.10; washout rate, 20+/-3 to 34+/-3, P<0.05). Myocardial perfusion was improved only in the ischemic area treated with the therapy. These beneficial effects persisted for 12 months. No procedural complications or adverse effects were noted.",
            "output": [
                "Does extracorporeal cardiac shock wave therapy ameliorate myocardial ischemia in patients with severe coronary artery disease?"
            ]
        },
        {
            "id": "task847-8dc8d27bfaeb451ba0812c6f6e98dc24",
            "input": "Earlier studies regarding the risk of colorectal cancer in women with a prior diagnosis of breast cancer yielded conflicting results.', 'A retrospective cohort study was performed using the General Practitioner Research Database of the United Kingdom. Women with a prior diagnosis of breast cancer were compared with female control patients without a prior history of breast cancer. The primary outcome was an incident diagnosis of colorectal cancer. Poisson regression analysis was utilized to assess the effects of potential confounder variables.', 'The study included 17,415 breast cancer patients and 69,660 matched control patients with follow-up time in person years of 52,914 and 331,480, respectively. The relative rate of colorectal cancer among breast cancer patients was 0.80 (95% CI 0.56-1.15). The relative rate of colorectal cancer among women exposed and unexposed to tamoxifen were 0.73 (95% CI 0.49-1.08) and 1.81 (95% CI 0.85-3.85), respectively.",
            "output": [
                "Are women with a prior diagnosis of breast cancer at an increased risk for subsequent colorectal cancer?"
            ]
        },
        {
            "id": "task847-01527424f64a45d49892f8f891ac372e",
            "input": "To investigate the effect of patellar taping on the amplitude of electromyographic activity (EMG) of vasti activation in subjects with and without patellofemoral pain (PFP).', 'Ten participants with PFP and 12 asymptomatic controls were recruited to the study. The study was designed as a randomised crossover trial. Participants completed a stair stepping task. Three experimental conditions were assessed: no tape, therapeutic medially directed tape, and placebo vertically directed tape. The main outcome measure was the EMG amplitude of the vastus medialis obliquus and vastus lateralis during the concentric phase of stair stepping.', 'The application of medially directed therapeutic tape significantly decreased pain in subjects with PFP. However, application of tape over the patella (therapeutic or placebo) did not alter the amplitude of vasti EMG when either the PFP or control participants completed the concentric stair stepping task.",
            "output": [
                "Does patellar taping change the amplitude of electromyographic activity of the vasti in a stair stepping task?"
            ]
        },
        {
            "id": "task847-61e7601aebb44a55ad058d36ce5f7abf",
            "input": "Although magnesium provides cerebral protection in animal stroke models, magnesium therapy has significant side effects in humans. Therefore, we sought to examine the incidence of alpha-agonist treated hypotension in our ongoing, prospective, randomized, double-blind, placebo-controlled Phase I/IIa dose escalation study of magnesium therapy in patients undergoing carotid endarterectomy.', 'Eighty patients undergoing elective carotid endarterectomy were randomly assigned to a placebo control group (n = 38) or to one of the three intravenous magnesium groups. Magnesium levels were obtained before induction, and then 15 minutes, 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after a loading dose and infusion. After surgery, a target systolic blood pressure range was chosen, and the amount and duration of phenylephrine needed to maintain that pressure was compared across treatment groups.', 'All treatment groups achieved levels significantly different from baseline at 12 and 24 hours (P < 0.01). Magnesium treatment did not significantly increase the proportion of patients requiring pressure support. For those requiring pressure support, the amount and average duration of phenylephrine required was not different between control patients and those receiving magnesium, even when the individual minimum systolic blood pressures required were subdivided on the basis of dose of magnesium administered.",
            "output": [
                "Are high dose magnesium infusions associated with increased pressor requirements after carotid endarterectomy?"
            ]
        },
        {
            "id": "task847-c5c8ac22391d49cb9bb56f69b1288c62",
            "input": "Subdural arrays of grid and strip electrodes are frequently used in epilepsy patients to localize the seizure focus and determine the location of critical brain functions via stimulation mapping. Postoperatively, the majority of patients with implanted subdural electrodes develop subacute extra-axial collections (EACs). Although conservative management is appropriate in most of these cases, occasionally patients manifest neurological symptoms that may necessitate reoperation for collection evacuation. Currently, there is little information available regarding the range of EAC size and the potential correlation between EAC size and symptom development. To facilitate treatment decision-making in postoperative subdural electrode patients, we reviewed and compared the computed tomographic (CT) features of postelectrode placement EACs in asymptomatic and symptomatic patients.', 'We retrospectively reviewed the medical records and CT scans of 22 consecutive patients who underwent craniotomy for placement of subdural grid and strip electrodes at Columbia University Medical Center. Medical records were reviewed for neurological complications from the time of grid placement until its removal. Each EAC was measured on CT for volume (% of total cranial volume), maximal thickness, and midline shift. One patient was excluded secondary to the development of an intracerebral hemorrhage.', 'Thirteen of 21 patients remained asymptomatic or minimally symptomatic during their hospitalization, with only mild to moderate, intermittent, postoperative headaches. The remaining eight developed symptoms such as persistent and severe headache, transient motor deficit, or speech impairment. Two of these patients underwent reoperation for hematoma evacuation. EACs in asymptomatic patients had a mean volume, maximal thickness, and midline shift of 5.7%, 1.25 cm, and 0.33 cm, respectively. EACs in symptomatic patients had a mean volume, maximal thickness, and midline shift of 7.7%, 1.46 cm, and 0.5 cm, respectively. Differences between maximal thickness and midline shift did not approach statistical significance. Despite this, the difference between the mean volume of symptomatic and asymptomatic EACs was statistically significant (P = 0.04).",
            "output": [
                "Do radiographic characteristics fail to predict clinical course after subdural electrode placement?"
            ]
        },
        {
            "id": "task847-598bdc941c4e4bf9a686f4555b7fdc0d",
            "input": "To evaluate whether the relationship between dietary composition and plasma lipid levels is genetically determined.', 'We have evaluated the influence of common apolipoprotein A5 (APOA5) variants (T-1131 > C, Ser19 > Trp and Val153 > Met) on plasma lipid concentrations in 117 males for whom dietary composition markedly changed and total cholesterol decreased (from 6.21 +/- 1.31 mmol/L in 1988 to 5.43 +/- 1.06 mmol/L in 1996) over an 8 year follow-up study.', 'APOA5 T-1131 > C and Val153 > Met variants did not influence the change in lipid measures over time. In Ser/Ser19 homozygotes, the plasma cholesterol was relatively stable over the years (6.1 +/- 1.2 mmol/L in 1988 and 5.6 +/- 1.0 mmol/L in 1996, -8%, P < 0.01). In contrast, in the Trp19 carriers, the decrease of the plasma cholesterol was more than 20% (6.5 +/- 1.6 mmol/L in 1988 and 5.1 +/- 1.0 mmol/L in 1996) (P < 0.001). The difference of the changes is significant (8% vs. 20%, P < 0.005). Changes in other analyzed lipid parameters have not been significantly associated with APOA5 variants.",
            "output": [
                "Does aPOA5 variant Ser19Trp influence a decrease of the total cholesterol in a male 8 year cohort?"
            ]
        },
        {
            "id": "task847-4d104e3b248b4cda81e1afc63df52b68",
            "input": "To investigate the pattern of perfusion abnormalities in ictal and interictal brain perfusion SPECT images (BSI) from patients with temporal lobe epilepsy (TLE).', 'It was acquired interictal and ictal BSI from 24 patients with refractory TLE. BSIs were analyzed by visual inspection and statistical parametric mapping (SPM2). Statistical analysis compared the patients group to a control group of 50 volunteers. The images from patients with left-TLE were left-right flipped.', 'It was not observed significant perfusional differences in interictal scans with SPM. Ictal BSI in SPM analysis revealed hyperperfusion within ipsilateral temporal lobe (epileptogenic focus) and also contralateral parieto-occipital region, ipsilateral posterior cingulate gyrus, occipital lobes and ipsilateral basal ganglia. Ictal BSI also showed areas of hypoperfusion.",
            "output": [
                "Does statistical voxel-wise analysis of ictal SPECT reveal pattern of abnormal perfusion in patients with temporal lobe epilepsy?"
            ]
        },
        {
            "id": "task847-eb0e8c9bd8784946b498e8b83dfbcc0d",
            "input": "Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation is one proposed mechanism of the valvulopathy observed in individuals treated with the appetite suppressants fenfluramine and phentermine. One key protein limiting systemic availability of 5-HT is the 5-HT transporter (5-HTT) expressed by platelets and pulmonary vascular cells; 5-HTT is responsible for 5-HT uptake and subsequent inactivation of the amine passing through the lung. Here we investigated whether 5-HTT-deficient (5-HTT-KO) mice developed structural and/or functional cardiac abnormalities and valvulopathy.', 'Cardiac endothelial cells expressed large amounts of 5-HTT in wild-type mice. 5-HTT deficiency appeared to be associated with marked interstitial, perivascular, and valvular fibrosis as evidenced by staining of cardiac collagen in 5-HTT-KO mice. Histological analysis provided evidence for valvulopathy characterized by valvular hyperplasia and prominent fibrosis at the attachment site and base of the leaflets. Echocardiography revealed an increase in left ventricular lumen diameter and a decrease in left ventricular diameter fractional shortening. Although 5-HT1B receptors mediated the 5-HT-induced collagen secretion by human cardiac myofibroblasts, the contribution of this receptor type to valvulopathy was ruled out because double-KO mice deficient in both 5-HTT and 5-HT1B receptors showed the same cardiac alterations as 5-HTT-KO mice.",
            "output": [
                "Does deficiency of the 5-hydroxytryptamine transporter gene lead to cardiac fibrosis and valvulopathy in mice?"
            ]
        },
        {
            "id": "task847-f99dc846e5ef46729ac8eb01ae92fe25",
            "input": "The present study was aimed at evaluating the outcome of pregnancies with nuchal cord.', 'A retrospective population-based study of all deliveries during the years 1988-2003 in a tertiary medical center was conducted. Immediate perinatal outcome of patients with and without nuchal cord was compared.', 'Of 166,318 deliveries during the study period, 14.7% had a nuchal cord, documented at birth (n=24,392). Higher rates of labor induction and non-reassuring fetal heart rate patterns were noted among pregnancies with nuchal cord as compared with the control group (30.1% vs. 24.2%; OR=1.3, 95% CI 1.3-1.4, P<0.001 and 4.5% vs. 2.6%; OR=1.8, 95% CI 1.6-1.9, P<0.001; respectively). The cesarean delivery rate was significantly lower among pregnancies with nuchal cord (11.5% vs. 12.7%; OR=0.9, 95% CI 0.8-0.9, P=0.001). Although 1 min Apgar scores lower than 7 were more common in pregnancies with nuchal cord (4.8% vs. 4.4%; OR=1.1, 95% CI 1.01-1.2, P=0.008), these pregnancies actually had lower rates of 5 min Apgar scores less than 7 (0.5% vs. 0.7%; OR=0.8, 95% CI 0.6-0.9, P=0.004). Likewise, the perinatal mortality rate was significantly lower in pregnancies with nuchal cord as compared with the comparison group (11/1,000 vs. 16/1,000; OR=0.7, 95% CI 0.6-0.8, P=0.001).",
            "output": [
                "Is nuchal cord associated with adverse perinatal outcome?"
            ]
        },
        {
            "id": "task847-456cd9120fc24dc4b52dd797c6300367",
            "input": "Patch closure after carotid endarterectomy (CEA) improves clinical outcome compared with primary closure. Whether there are differences in outcome between various patch materials is still not clear. The objective of this retrospective study was to investigate whether a relationship exists between the patch type and the number of microemboli as registered during CEA by transcranial Doppler imaging, the clinical outcome (transient ischemic attack and cerebrovascular accident), and the occurrence of restenosis.', 'We included 319 patients who underwent CEA. Intraoperative microembolus registration was performed in 205 procedures. Microembolization was recorded during four different periods: dissection, shunting, clamp release, and wound closure. The decision to perform primary closure or to use a patch for the closure of the arteriotomy was made by the surgeon, and Dacron patches were used when venous material was insufficient. Cerebral events were recorded within the first month after CEA, and duplex scanning was performed at 3 months (n = 319) and 1 year (n = 166) after CEA. A diameter reduction of more than 70% was defined as restenosis.', 'Primary, venous, and Dacron patch closures were performed in 83 (26.0%), 171 (53.6%), and 65 (20.4%) patients, respectively. Primary closure was significantly related to sex (Dacron patch, 35 men and 30 women; venous patch, 108 men and 63 women; primary closure, 72 men and 11 women; P < .001). The occurrence of microemboli during wound closure was also related to sex (women, 2.5 +/- 0.6; men, 1.0 +/- 0.2; P = .01). Additionally, during clamp release, Dacron patches were associated with significantly more microemboli than venous patches (11.1 +/- 3.4 vs 4.0 +/- 0.9; P < .01), and this difference was also noted during wound closure (3.1 +/- 0.9 vs 1.4 +/- 0.4; P < .05). Transient ischemic attacks and minor strokes after CEA occurred in 5 (2.4%) of 205 and 6 (2.9%) of 205 procedures, respectively, and the degree of microembolization during dissection was related to adverse cerebral events (P = .003). In contrast, the type of closure was not related to immediate clinical adverse events. However, primary closure and Dacron patches were associated with an increase in the restenosis rate compared with venous patches: after 400 days, the restenosis rate for Primary closure was 11%, Dacron patch 16%, and venous patch 7% (P = .05; Kaplan-Meier estimates).",
            "output": [
                "Is closure of the arteriotomy after carotid endarterectomy : patch type related to intraoperative microemboli and restenosis rate?"
            ]
        },
        {
            "id": "task847-7ed8c903dc9f4eaa82965288fa310bff",
            "input": "Brain injury after hypoxic-ischemic insults evolves via an apoptotic/necrotic cascade. Glutamate over release and N-methyl-d-aspartate (NMDA) receptor over activation (excitotoxicity) are believed to trigger this process. Xenon is a nontoxic anesthetic gas that reduces neurotransmitter release and functionally antagonizes NMDA receptors. Administering xenon to hypoxic-ischemic newborns might be clinically effective if the neurotoxic processes continue evolving after delivery. We sought to determine whether xenon administration after the initial hypoxic-ischemic insult was neuroprotective.', 'Fifty 7-day-old rats received a 90-minute hypoxic insult after unilateral carotid ligation. They were then randomized to breathe 1 of 2 gas mixtures for 3 hours: 50% Xe/30% O2/20% N2 or 30% O2/70% N2.', 'One week after hypoxic-ischemic survival, significant global protection was seen in the xenon group (80% less injury); cortex/white matter (88% versus 25%), hippocampus (62% versus 0%), basal ganglia (81% versus 25%), and thalamus (50% versus 0%; percentage of global damage score in nonxenon versus xenon groups, respectively).",
            "output": [
                "Does xenon provide short-term neuroprotection in neonatal rats when administered after hypoxia-ischemia?"
            ]
        },
        {
            "id": "task847-2528b8084ee941a08f481700c6f0f0c4",
            "input": "C-type natriuretic peptide (CNP) is an important regulator of skeletal growth. Loss-of-function mutations affecting the CNP receptor natriuretic peptide receptor-B (gene NPR2) cause the autosomal recessive skeletal dysplasia, acromesomelic dysplasia, Maroteaux type (AMDM). The phenotype of heterozygous carriers of NPR2 mutations is less clear.', 'The objective of the study was to determine the phenotypic features of heterozygous carriers of NPR2 mutations.', 'This was a case-control study from the general community.', 'Thirty-nine members of a family in which one member has AMDM were studied.', 'This was an observational study.', 'The primary measure was stature, with the hypothesis that carriers have reduced stature compared with noncarriers.', 'Sixteen family members were NPR2 mutation carriers. Height z-scores of these carriers were -1.8 +/- 1.1 (mean +/- sd), which was significantly less than the 23 noncarrier family members (-0.4 +/- 0.8, P < 0.0005) and the general population (P < 0.0005). However, there was no difference in body proportion between carriers and noncarriers. The proband with AMDM had low IGF-I levels and evidence of GH resistance, as well as very high plasma levels of CNP and its amino-terminal propeptide. Levels of these peptides were normal in the heterozygous carriers.",
            "output": [
                "Are heterozygous mutations in natriuretic peptide receptor-B ( NPR2 ) associated with short stature?"
            ]
        },
        {
            "id": "task847-688a814e3fb74a0caa20230cb02e8e1e",
            "input": "Insulin resistance is a central feature of type 2 diabetes. Salicylates prevent lipid-induced insulin resistance in rodents by interrupting inflammatory pathways. We therefore investigated whether salicylates reduce lipid-induced insulin resistance in humans by affecting inflammatory pathways as reflected by serum adipocytokines.', 'Ten healthy men were included in a crossover intervention study. Four euglycemic-hyperinsulinemic clamps were performed, one without pretreatment, one with prior 2-h lipid infusion, one after pretreatment with 4 g acetylsalicylic acid (ASA), and one with ASA pretreatment and prior lipid infusion.', 'Lipid-induced insulin resistance was quantified by the euglycemic-hyperinsulinemic clamp technique running at least 2 h. Repeated-measures ANOVA on two factors was used for comparison, and results were Bonferroni adjusted for multiple measurements. ASA effects on serum adipocytokines were addressed by comparing the areas under the curves.', \"Glucose infusion rate (M value) of the control clamp without pretreatment was 6.3 (+/- 0.6) mg/kg.min. ASA pretreatment did not change glucose infusion rates (P = 0.6). Lipid infusion significantly decreased the M value to 4.1 (+/- 0.6) mg/kg.min (P = 0.008). After ASA pretreatment and lipid infusion, the M value was 4.8 (+/- 0.7) mg/kg.min and was significantly improved, compared with the lipid-only clamp (P = 0.036 after Bonferroni's adjustment). General biomarkers of inflammatory processes (IL-6, C-reactive protein), the insulin-sensitizing mediator adiponectin, and circulating adiponectin oligomers were unchanged by ASA pretreatment.",
            "output": [
                "Does acetylsalicylic acid improve lipid-induced insulin resistance in healthy men?"
            ]
        },
        {
            "id": "task847-f5dceb70ae7b432a93ebc894613f18af",
            "input": "Recurrence and cisplatin resistance that progressively develops in the course of treatments are major impediments in ovarian cancer therapy. We investigated the involvement of alterations of different signaling pathways in this acquired chemoresistance.', 'We studied the activation of these pathways in a model of progressive acquisition of resistance that we established, by discontinuously exposing a sensitive ovarian carcinoma cell line, OAW42, to increasing concentrations of cisplatin.', 'OAW42-T1 and -T2 variants, which emerged after the first two treatments of OAW42 cells with 5 microg/ml cisplatin, showed enhanced but transient resistance. OAW42-R cells, obtained following successive reiterations of the treatment, displayed both a stronger resistance to cisplatin-induced apoptosis and an increased capacity to recover a normal proliferation after treatment. The measurement of DNA adducts demonstrated that the mechanisms leading to a decreased DNA platination could not explain the level of resistance of OAW42-R cells. The simultaneous study of activation pattern of key proteins of different signaling pathways revealed that cisplatin induced both activation of ERK and p38 and inhibition of P-FAK in the sensitive cells, whereas it progressively failed to elicit such a response in the resistant variants. In contrast, STAT3 and Akt did not seem to be involved in the acquired chemoresistance in our model.",
            "output": [
                "Is acquisition of chemoresistance following discontinuous exposures to cisplatin associated in ovarian carcinoma cells with progressive alteration of FAK , ERK and p38 activation in response to treatment?"
            ]
        },
        {
            "id": "task847-8f6a6bba419c43048e3c8d21eb350c67",
            "input": "Total IgE levels positively correlate with the amount of mucosal thickening on sinus CT scans. Our objective was to investigate whether the levels of total serum IgE decreased 1 year after endoscopic sinus surgery in patients with chronic rhinosinusitis, suggesting that the total IgE was influenced by the sinus disease.', '55 patients about to undergo endoscopic sinus surgery for chronic rhinosinusitis were enrolled in a prospective clinical study. All patients had preoperative sinus computerized tomography (CT) scans and levels of total serum IgE measured before surgery and 1 year postoperatively.', 'Preoperative total IgE levels showed a significant correlation with the extent of disease on sinus CT (r(s) = 0.413, p = 0.002). Total serum IgE levels did not show any statistically significant change from the preoperative values when measured 1 year postoperatively (324.25 +/- 217.30 ng/ml vs. 326.35 +/- 204.50 ng/ml; p = 0.61).",
            "output": [
                "Do total IgE levels change 1 year after endoscopic sinus surgery in patients with chronic rhinosinusitis?"
            ]
        },
        {
            "id": "task847-1cbd3cdcc0a24a17a0a705f9df825a87",
            "input": "Uterine vascular remodeling at mid gestation includes the thinning of the vessel walls and, typically, an increase in lumen diameter. This study aimed to elucidate any differences in structural remodeling in normal murine pregnancies versus those differences that resulted from the crossing of CBA/J female mice by DBA/2 male mice, a combination that is known to exhibit recurrent resorption/pregnancy loss.', 'CBA/J female mice that were pregnant by DBA/2 male mice (abnormals) and DBA/2 female mice that were pregnant by CBA/J male mice (normals) were killed at mid gestation, which is a time when fetal resorption can be identified. Tissues were collected for permanent fixation and gene expression studies with complementary DNA macroarrays that were specific for extracellular matrix proteins. A 2-fold increase in expression or a 50% decline was considered significant. Expression changes were confirmed by real-time reverse transcriptase-polymerase chain reaction.', 'The vessel-to-lumen diameter ratios were found to be significantly greater for the CBA/J implantation sites (1.50 +/- 0.05 vs 1.22 +/- 0.02, respectively; P < .0001), which indicates a lack of vascular remodeling. There was also a trend towards smaller lumen diameters for the CBA/J vessels, but this was not statistically significant (78.2 +/- 4.4 microm vs 93.5 +/- 6.8 microm, respectively; P = .22). The mean coefficient of variation for lumen measurements was 0.8% and for vessel diameter was 0.3%. The ranges were 0 to 3.2% and 0 to 1.4%, respectively. Tissue inhibitor of metalloproteinase 2 expression was up-regulated in the placentas of the group with higher resorption rates when compared with normals. This was confirmed with reverse transcriptase-polymerase chain reaction, where abnormals exhibited 2.6-fold greater tissue inhibitor of metalloproteinase 2 protein quantities when compared with normal controls (P = .03).",
            "output": [
                "Is failure of decidual arteriolar remodeling in the CBA/J x DBA/2 murine model of recurrent pregnancy loss linked to increased expression of tissue inhibitor of metalloproteinase 2 ( TIMP-2 )?"
            ]
        },
        {
            "id": "task847-14eb4f0029f24311addcabd6f4a48084",
            "input": "Low back pain (LBP) and sciatica are usually caused by degenerative disc disease (DDD). Although they are common, the etiology of these conditions is poorly understood. A large population case-control study in the Southern Chinese was performed to study genetic risk factors to DDD.', 'To gain a better understanding of the etiology of DDD in relation to structural defects of the intervertebral disc.', 'A Finnish study found an association between LBP and sciatica with two variants of the alpha-chains of collagen IX, encoded by the Trp2 and Trp3 alleles, representing Gln326Trp and Arg103Trp amino acid substitutions in the COL9A2 and COL9A3 genes, respectively. Trp2 was found only in affected individuals (4%), whereas Trp3 was present in both affected (24%) and unaffected (9%) individuals. Because of the low frequency of the Trp2 allele in whites, the significance and contribution of this allele to DDD are not known. Using more objective criteria to define the disease by magnetic resonance imaging (MRI), we tested these alleles for association with DDD in a large population study.', 'Lumbar DDD, the presence of anular tears, and disc and endplate herniations were defined by MRI in 804 Southern Chinese volunteers 18 to 55 years of age. These were correlated with the frequencies of the Trp2 and Trp3 alleles.', 'The Trp2 allele was present in 20% of the population and was associated with a fourfold increase in the risk of developing anular tears at 30 to 39 years and a 2.4-fold increase in the risk of developing DDD and endplate herniations at 40 to 49 years. Affected Trp2 individuals had more severe degeneration. The Trp3 allele was absent from the Southern Chinese population.",
            "output": [
                "Is the TRP2 allele of COL9A2 an age-dependent risk factor for the development and severity of intervertebral disc degeneration?"
            ]
        },
        {
            "id": "task847-8eb1785cbec94d5a8fcaa56dbb26403e",
            "input": "Although it has been postulated that liver injury results in impaired clearance of bacteria from the blood, no prior study has evaluated hepatic bacterial clearance during sepsis.', 'We hypothesized that liver injury during the evolution of sepsis would result in impaired hepatic bacterial clearance.', 'Mild and severe bacteremia were generated in C57BL/6 mice by low- and high-dose intratracheal inoculation with Pseudomonas aeruginosa.', 'The mortality rates with mild and severe bacteremia were 20% and 60%, respectively. Hepatic bacterial clearance was preserved throughout the evolution of mild bacteremia but was lost late with severe bacteremia. The loss of hepatic bacterial clearance resulted in increased systemic bacteremia and mortality. Pretreatment with a caspase inhibitor resulted in preservation of hepatic bacterial clearance with severe bacteremia and eventual control of the bacteremia. When Kupffer cells were ablated before the onset of bacteremia, there was a loss of hepatic bacterial clearance. This converted an initially mild bacteremia into severe bacteremia with increased organ injury and mortality.",
            "output": [
                "Does severe bacteremia result in a loss of hepatic bacterial clearance?"
            ]
        },
        {
            "id": "task847-13f74b066fd945fd925a8c87c46bb1c4",
            "input": "Although the continuity equation remains the noninvasive standard, planimetry using transesophageal echocardiography is often used to assess valve area for patients with aortic stenosis (AS). Not uncommonly, however, anatomic valve area (AVAA) obtained by planimetry overestimates continuity-derived effective valve area (AVAE) in bicuspid AS.', 'Transthoracic Doppler and transesophageal echocardiography were performed to obtain AVAE and AVAA in 31 patients with bicuspid AS (age 61 +/- 11 years) and 22 patients with degenerative tricuspid AS (age 71 +/- 13 years). Aortic root and left ventricular outflow tract dimensions and the directional angle of the stenotic jet were assessed in all patients. Using these data, a computational fluid dynamics model was constructed to test the effect of these variables in determining the relationship between AVAE and AVAA.', 'For patients with tricuspid AS, the correlation between AVAA (1.15 +/- 0.36 cm2) and AVAE (1.13 +/- 0.46 cm2) was excellent (r = 0.91, P < .001, Delta = 0.02 +/- 0.21 cm2). However, AVAA was significantly larger (1.19 +/- 0.35 cm2) than AVAE (0.89 +/- 0.29 cm2) in the bicuspid AS group (r = 0.71, P < .001, Delta = 0.29 +/- 0.25 cm2). Computer simulation demonstrated that the observed discrepancy related to jet eccentricity.",
            "output": [
                "Does planimetric assessment of anatomic valve area overestimate effective orifice area in bicuspid aortic stenosis?"
            ]
        },
        {
            "id": "task847-545b5c14883d4098958b59305bb3456c",
            "input": "Alterations of fibroblast growth factors (FGFs) and their receptors contribute to prostate cancer progression by enhancing cellular proliferation, survival, and motility. The Sprouty gene family negatively regulates FGF signaling and may limit the ability of FGFs to enhance tumor progression. Sprouty1 is down regulated in human prostate cancers and Sprouty1 expression can markedly inhibit prostate cancer proliferation in vitro. Sprouty4 has been shown to negatively regulate both proliferation and cell migration in other systems. We therefore examined whether Sprouty4 expression was altered in prostate cancer.', 'Expression of Sprouty4 was examined by in situ hybridization and quantitative RT-PCR. Methylation of the Sprouty4 gene promoter was assessed using bisulfite modification and sequencing. The effect of Sprouty4 expression on cell migration was determined using an in vitro wounding assay.', \"By in situ hybridization Sprouty4 is expressed in normal prostatic epithelial cells and is decreased in a subset of prostate cancers. Quantitative RT-PCR confirms that Sprouty4 expression is decreased in approximately one half of prostate cancers. Analysis of the 5'-regulatory region revealed a CpG island approximately 1 kb upstream of the transcription initiation site, the proximal portion of which was preferentially methylated in prostate cancer tissues. More than one half of all prostate cancer DNAs were methylated in this region and methylation was significantly correlated with decreased Sprouty4 expression as determined by quantitative RT-PCR. When overexpressed in prostate cancer cell lines, Sprouty4 did not inhibit cell proliferation but did inhibit cell migration.",
            "output": [
                "Is sprouty4 , a suppressor of tumor cell motility , down regulated by DNA methylation in human prostate cancer?"
            ]
        },
        {
            "id": "task847-f4cc1b0342cf443881a259faf8543c69",
            "input": "Fingertip injuries are common and bear significant costs associated with treatment, lost work, and functional impairment. This study compared these factors in occupationally related fingertip injuries treated with becaplermin, a recombinant human platelet-derived growth factor, and those treated with surgical reconstruction.', 'This was a prospective controlled trial involving occupationally related fingertip injuries. Fifty men (ages 23-51) with full thickness, single fingertip injuries > or =1.5 cm(2) with or without phalangeal exposure and distal to the distal interphalangeal (DIP) joint were evaluated. Group I (n = 25) underwent treatment with daily topical becaplermin. Group II (n = 25) underwent surgical reconstruction with a skin graft or local soft tissue flap. Time to wound healing, time to return to work, associated treatment costs, and calculated functional impairment were recorded.', 'Patients in Group I returned to work in significantly less time than those in Group II-10 days versus 38 days respectively). The average calculated functional impairment in Group I was 10% versus 22% in Group II. Associated treatment costs in group A were 1580 +/- 145 US Dollars compared with 6750 +/- 785 US Dollars in Group II. All differences were statistically significant at p < 0.05",
            "output": [
                "Does topical becaplermin improve outcomes in work related fingertip injuries?"
            ]
        },
        {
            "id": "task847-09e45c1d8ea74052a67b5c13d8100ae4",
            "input": "To investigate the effect of the X-linked immunodeficiency (Xid) B cell defect on the response to the cockroach allergen in mice.', 'Two cockroach allergen immunization and challenge protocols were employed to sensitize CBA/J wild-type and CBA/CaHN-btk(-/-)xid/J (Xid) mice. Blood and tissue samples were collected 24 and 48 hrs after the last intratracheal antigen challenge and were analyzed for several parameters of allergic inflammation.', 'Nearly equivalent amounts of serum IgE were detected in Xid and CBA/J mice after short-term antigen challenge despite the B cell deficiency in Xid mice. A decreased concentration of IgE was detected in CBA/J mice after repeated allergen challenges but not in the Xid mice. Correlating with the discrepancy in serum IgE levels, higher levels of IL-13, IL-5, IL-10 and CCL5 were measured in whole lung homogenates from allergen-challenged Xid mice compared to CBA/J mice. In addition, draining lymph node cells from Xid mice expressed elevated levels of IL-4, IL-5, IL-10 and IFNgamma mRNA compared to cells from CBA/J mice after in vitro culture with cockroach antigen. An increase in lung inflammation, interstitial eosinophilia and mucus production was also observed in allergen-challenged Xid mice. CD95L expression increased on B-1a cells following allergen challenge, which was accompanied by an increase in lung CD4(+) Th cell apoptosis in wild-type CBA/J mice. In contrast, Xid mice did not have an increase in CD4(+) T cell apoptosis following allergen challenge.",
            "output": [
                "Does deficiency of regulatory B cells increase allergic airway inflammation?"
            ]
        },
        {
            "id": "task847-7d35a5228bea4d0dbf23f90baa83d232",
            "input": "Androgen ablation is the standard initial treatment for advanced prostate cancer; however, tumors eventually develop androgen independence and become incurable. Chemotherapy is commonly used after hormone treatment fails but has not shown significant survival benefit. Studies suggest that androgen ablation can select for a population of hormone-independent cells that are also relatively chemotherapy resistant. Thus, it may be therapeutically advantageous to target prostate cancer with chemotherapy before hormone ablation. This study was undertaken to determine the relative efficacy of such an approach in a preclinical model of prostate cancer.', 'Severe combined immunodeficient mice bearing human LNCaP prostate tumors were treated with docetaxel and/or surgical castration applied singly, concurrently, or in different sequences. Treatment efficacy was determined by tumor volume and growth delay measurements. The extent of apoptosis in tumors in response to treatments was assessed via terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assays. In addition, Western blots were done to study the relative expression of Bcl-2 and Bax in the tumors.', 'Docetaxel followed by castration showed the most potent antitumor effects. In contrast, with the exception of castration alone, castration followed by docetaxel produced the least antitumor activity. TUNEL assays confirmed that the density of apoptotic tumor cells was significantly greater for docetaxel followed by castration than for any other treatment. In tumors of mice treated with single modality therapies, Bax to Bcl-2 ratios decreased significantly after castration, whereas this ratio remained high after docetaxel treatment.",
            "output": [
                "Does docetaxel followed by castration improve outcomes in LNCaP prostate cancer-bearing severe combined immunodeficient mice?"
            ]
        },
        {
            "id": "task847-95c740f344ef4749aaa8bd8c84632f4b",
            "input": "Studies have demonstrated that patients with Barrett's oesophagus have the highest oesophageal acid exposure profile, followed by erosive oesophagitis and non-erosive reflux disease patients, but the exact extent of overlap remains unknown.\", 'To determine the extent of overlap in oesophageal acid exposure among the different gastro-oesophageal reflux disease groups.', \"A total of 121 patients with gastro-oesophageal reflux disease underwent an upper endoscopy and were classified as having Barrett's oesophagus, erosive oesophagitis and non-erosive reflux disease-all (non-erosive reflux disease-positive and functional heartburn). Subsequently, patients underwent pH testing and overlap in oesophageal acid exposure among the different gastro-oesophageal reflux disease groups was determined.\", \"Of those enrolled, 24 had Barrett's oesophagus, 30 erosive oesophagitis and 28 were non-erosive reflux disease-positive. Mean oesophageal acid exposure time was 224.8 +/- 35, 134.3 +/- 21.9 and 141.3 +/- 19.8 min for Barrett's oesophagus, erosive oesophagitis and non-erosive reflux disease-positive respectively. Per cent overlap for total, upright and supine time between non-erosive reflux disease-positive and erosive oesophagitis was 47.4%, 64.7% and 81.8%, between Barrett's oesophagus and erosive oesophagitis was 47.8%, 40.7% and 24%, and between Barrett's oesophagus and non-erosive reflux disease-positive was 31.6%, 37.5% and 20.8% respectively.",
            "output": [
                "Do the extent of oesophageal acid exposure overlap among the different gastro-oesophageal reflux disease groups?"
            ]
        },
        {
            "id": "task847-e56924e7058642a8ae24375377466dcb",
            "input": "Previous study in human subjects has documented biomechanical and neurophysiological responses to impulsive spinal manipulative thrusts, but very little is known about the neuromechanical effects of varying thrust force-time profiles.', 'Ten adolescent Merino sheep were anesthetized and posteroanterior mechanical thrusts were applied to the L3 spinous process using a computer-controlled, mechanical testing apparatus. Three variable pulse durations (10, 100, 200 ms, force = 80 N) and three variable force amplitudes (20, 40, 60 N, pulse duration = 100 ms) were examined for their effect on lumbar motion response (L3 displacement, L1, L2 acceleration) and normalized multifidus electromyographic response (L3, L4) using a repeated measures analysis of variance.', 'Increasing L3 posteroanterior force amplitude resulted in a fourfold linear increase in L3 posteroanterior vertebral displacement (p < 0.001) and adjacent segment (L1, L2) posteroanterior acceleration response (p < 0.001). L3 displacement was linearly correlated (p < 0.001) to the acceleration response over the 20-80 N force range (100 ms). At constant force, 10 ms thrusts resulted in nearly fivefold lower L3 displacements and significantly increased segmental (L2) acceleration responses compared to the 100 ms (19%, p = 0.005) and 200 ms (16%, p = 0.023) thrusts. Normalized electromyographic responses increased linearly with increasing force amplitude at higher amplitudes and were appreciably affected by mechanical excitation pulse duration.",
            "output": [
                "Do spinal manipulation force and duration affect vertebral movement and neuromuscular responses?"
            ]
        },
        {
            "id": "task847-9aedbcad8a7a4268878bb946f60aa0ca",
            "input": "A prospective radiographic analysis of deformity correction during the balloon kyphoplasty procedure.', 'To determine the spontaneous reduction of the deformity in prone position, the subsequent deformity correction by the inflatable bone tamp, and the overall deformity correction after deposition of the cement.', 'Fracture mobility has been shown to contribute to fracture reduction in vertebroplasty. Spontaneous reduction has not been taken into account in recently published series of balloon kyphoplasty, but it must be considered when performing vertebral augmentation and when reporting and interpreting the significance of vertebral height restoration.', 'A consecutive series of 39 osteoporotic vertebral compression fractures were treated in 30 patients. Lateral radiographs were taken and analyzed at six different time points: 1) Preoperative standing. During the kyphoplasty procedure, four consecutive radiographs were obtained: 2) after placing the patient in prone position on the operation table, 3) after inflation of the bone tamp (IBT), 4) after deflation and removal of the IBT, and 5) after deposition of the cement. 6) Standing lateral radiographs were taken after the procedure. All fractures were analyzed for improvement in sagittal alignment (Cobb angle, kyphotic angle, sagittal index, vertebral height), complications, and reduction of pain (VAS).', 'Placement of the patient in prone position displayed a significant spontaneous reduction in deformity of 6.5 degrees +/- 4.1 degrees Cobb angle. Inflation of the IBT demonstrated a further reduction of the fracture and a significant improvement of the Cobb angle of 3.4 degrees compared with baseline prone. After deflation and removal of the IBT and placement of the cement, no significant loss of fracture reduction was seen. Postoperative measurement of the Cobb angle by means of standing radiographs demonstrated a 3.1 degrees significant loss of reduction compared with the intraoperative measurement in prone position after cement application. Cement leaks occurred in 9 of 39 vertebral fractures. All patients subjectively reported immediate relief of their typical fracture pain. The VAS score significantly improved from 8.7 +/- 1.4 before surgery to 2.3 +/- 0.9.",
            "output": [
                "Is balloon kyphoplasty effective in deformity correction of osteoporotic vertebral compression fractures?"
            ]
        },
        {
            "id": "task847-e05aa62c1ce1416980222182c5491909",
            "input": "The ability of CD8(+) T-cells to induce prostate inflammation was examined using a prostate ovalbumin expressing transgenic mouse (POET) and/or adoptive transfer of T-cell receptor (TCR) transgenic T-cells (OT-I) that specifically recognize ovalbumin. Localization of inflammatory cells to prostate tissue was examined following T-cell activation via endogenous prostatic antigen, recombinant type 5 adenovirus carrying the gene coding ovalbumin (Ad5-mOVA), or adoptive transfer of in vitro antigen stimulated OT-I cells.', 'Ovalbumin specific OT-I cells were activated by autologous prostate antigen and trafficked to the prostate, but did not induce inflammation unless present in overwhelming numbers ( approximately 65% of CD8(+) T-cells). Activation of antigen specific CD8(+) T-cells in vitro (peptide pulsed antigen presenting cells) or in vivo (Ad5-mOVA) induced transitory prostate inflammation, without induction of prostate pathology, regardless of CD4(+) T-cell availability. Inflammation also was observed in OT-I x POET mice but again, pathological effects were not observed.",
            "output": [
                "Is t-cell recognition of a prostate specific antigen sufficient to induce prostate tissue destruction?"
            ]
        },
        {
            "id": "task847-2c7f1fef19a9483497b8da1a6c2969ac",
            "input": "Inadequate response of the innate immune system to bacterial antigens present in the intestinal flora may play a role in the development of necrotizing enterocolitis (NEC). Pattern recognition receptors such as CD14, toll-like receptor (TLR) 4, and caspase-recruitment domain (CARD) 15 bind bacterial lipopolysaccharide and peptidoglycan, and their activation leads to production of inflammatory cytokines. Our aim was to evaluate whether single nucleotide polymorphisms (SNPs) of CD14, TLR4, and CARD15 are associated with the risk of NEC in very low birth weight (VLBW) infants.', 'We determined the CD14 C-260T, TLR4 A +896G, C +1196T, and CARD15 G +2722C, C +2104T, 3020insC functional SNPs in dried blood samples from 118 VLBW infants (of those, 41 developed NEC) and from 146 healthy term newborns using polymerase chain reaction and restriction fragment length polymorphism methods. We tested the association between genotype and risk of NEC.', 'No significant differences were found in the prevalence of CD14 -260T, TLR4 +896G, +1196T, and CARD15 +2722C, +2104T, 3020insC alleles between VLBW infants and healthy term newborns (P = NS). The frequencies of investigated genotypes were similar in infants with and without NEC (P = NS). Furthermore, we did not find any association between genotype and prematurity or sepsis, which are important risk factors of NEC.",
            "output": [
                "Are genetic polymorphisms of CD14 , toll-like receptor 4 , and caspase-recruitment domain 15 associated with necrotizing enterocolitis in very low birth weight infants?"
            ]
        },
        {
            "id": "task847-f652770323584a69a420d8080b1bec4f",
            "input": "To quantify the costs of treatment in critical limb ischaemia (CLI) and to compare costs and effectiveness of two treatment strategies: spinal cord stimulation (SCS) and best medical treatment.', 'One hundred and twenty patients with CLI not suitable for vascular reconstruction were randomised to either SCS in addition to best medical treatment or best medical treatment alone. Primary outcomes were mortality, amputation and cost. Cost analysis was based on resources used by patients for 2 years after randomisation. Both medical and non-medical costs were included.', 'Patient and limb survival were similar in the two treatment groups. Costs of in-hospital-stay and institutional rehabilitation constituted the predominant part (+/-70%) of the total costs of medical care in CLI. Cost of SCS-implantation and complications (7950 euro per patient) exceeded by far cost due to amputation procedures (410 euro per patient). The total costs of treatment were 36,600 euro per patient over 2 years for the SCS-group vs. 28,700 euro for best medical treatment alone (28% higher for SCS-group, p=0.009).",
            "output": [
                "Is spinal cord stimulation cost-effective for non-surgical management of critical limb ischaemia?"
            ]
        },
        {
            "id": "task847-a43829232ee9441dac0b24b3ce1c3d9b",
            "input": "Although moderate (conscious) sedation is intended during elective gastrointestinal endoscopy, unintended levels of deep sedation occur. The aims of this study were to prospectively evaluate the incidence and risk factors of deep sedation during elective endoscopy with meperidine and midazolam intended to maintain a level of moderate sedation.', \"Eighty American Society of Anesthesiology class 1-2, outpatients presenting for elective esophagogastroduodenoscopy (EGD), colonoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasonography (EUS) were offered enrollment. Intravenous meperidine and midazolam were administered according to a standardized protocol. Hemodynamic parameters and levels of sedation were assessed and recorded by a single observer at 3-min intervals. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale (ranging 1-5) is a subjective sedation assessment scale used to assess sedation levels. Occurrence of deep sedation, defined by MOAA/S 1-2, was recorded. Univariable and multivariable analyses were used to assess predictors of deep sedation.\", 'Deep sedation occurred in 54/80 (68%) patients for a total of 204/785 (26%) of total sedation assessments. The percentage of deep sedation episodes of all sedation-level observations by procedure was 26% for EGD, 11% for colonoscopy, 35% for ERCP, and 29% for EUS. Deep sedation occurred at least once in 60% of EGD, 45% of colonoscopy, 85% of ERCP, and 80% of EUS. Multivariable analysis showed that only ERCP and EUS were independent risk factors of deep sedation.",
            "output": [
                "Does deep sedation occur frequently during elective endoscopy with meperidine and midazolam?"
            ]
        },
        {
            "id": "task847-b10de37b4af14f0e8ac754db43d135e7",
            "input": "Interferons are known to inhibit the replication of hepatitis B viruses (HBV) in several animal models in vitro and in vivo as well in humans. The STAT-1 protein plays a central role in the biological activity of both type I and type II interferons. The lack of functional STAT-1 renders cells and organisms susceptible to bacterial and viral infectious agents. We analysed whether the overexpression of STAT-1 protein enhances the biological interferon response and whether it elicits antiviral activity against HBV in vitro.', 'To achieve an efficient STAT-1 overexpression in primary liver cells and hepatoma cells, we generated a recombinant, replication-deficient adenovirus expressing human STAT-1 (Adv-STAT-1). We analysed whether the overexpression of STAT-1 inhibits the replication of duck HBV and human HBV in vitro using Western blot analysis, the immunofluorescence of viral proteins and quantification of HBV-DNA copies, respectively.', 'In the duck model of HBV infection the overexpression of STAT-1 neither inhibited an established infection nor prevented the establishment of duck HBV replication when administered simultaneously with Adv-STAT-1. These observations were confirmed in an in-vitro model of human HBV infection using the human hepatoma cell line HepG2.2.15, which continuously replicates HBV.",
            "output": [
                "Does overexpression of STAT-1 by adenoviral gene transfer inhibit hepatitis B virus replication?"
            ]
        },
        {
            "id": "task847-fc42690857954c4096fcdd77a5cf02bc",
            "input": "To investigate whether our practice of specialist review of all diagnostic biopsies was necessary to prevent misgrading of referred prostate cancer patients, and whether this misclassification, if any, would have resulted in misclassification of clinical risk grouping (Seattle Risk Grouping [SRG]) and subsequent treatment strategy and prognosis.', 'Important prognostic indicators for prostate cancer include the presenting prostate-specific antigen (PSA), clinical stage and Gleason sum of the tumour. These three variables are incorporated into the SRG cohorts to establish treatment strategy. Patients with prostate cancer referred for brachytherapy had their prostate biopsies reviewed by a reference pathologist (PD) with a special interest in prostate cancer. We compared the agreement between the scoring of the referring pathologists with that of PD, and evaluated if any differences changed the SRG and therefore the clinical risk and treatment strategy for the patients.', \"In only 52% (43/83) of cases, was there total agreement between the two sets of pathologists. The inter-rater agreement was statistically 'fair' (unweighted kappa statistic 0.27). In 90% (36/40) of cases with disagreement, PD assigned higher Gleason sums. In 40% (16/40) of cases with disagreement, the change in Gleason sum altered the SRG; in one out of 16 cases, the SRG was downgraded from 'intermediate' to 'low' risk disease; in six out of 16 cases, it was upgraded from 'low' to 'intermediate' risk, and, in nine out of 16, from 'intermediate' to 'high' risk.",
            "output": [
                "Does gleason scoring vary among pathologists and this affects clinical risk in patients with prostate cancer?"
            ]
        },
        {
            "id": "task847-58d459c9d7e24d08a25f21675977c5cd",
            "input": "The objective was to evaluate the effect of dexamethasone and platelet transfusion treatment on recovery in patients with class 1 hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.', 'All women with class 1 HELLP syndrome (true HELLP syndrome) who were seen at the hospital Complejo Hospitalario de la Caja de Seguro Social de Panama, Panama between July 1996 and June 2004 took part in a retrospective, comparative study. They were divided into two groups. One group received dexamethasone and the other group received dexamethasone plus platelet transfusion. True HELLP syndrome was defined as hemolysis, elevated liver enzymes, and maternal platelet nadir < or =50,000 platelets/microl.', 'The primary endpoint was resolution of the HELLP syndrome as recognized by normalization of the platelet count (> or =150,000/microl) and the mean length (measured in days) of the postpartum stay in hospital.', 'Forty-six women with true HELLP syndrome were studied. Twenty-six patients received dexamethasone and 20 received dexamethasone plus platelet transfusion. The normalization of the platelet count was significantly more rapid in the dexamethasone group (p<0.004) and the postpartum hospital stay was significantly more prolonged in the dexamethasone plus platelet transfusion group (p<0.02). There was no maternal death.",
            "output": [
                "Does addition of platelet transfusions to corticosteroids increase the recovery of severe HELLP syndrome?"
            ]
        },
        {
            "id": "task847-4620aa73f3564edba1d27c48df0b4015",
            "input": "We sought to determine whether the flow-dependent changes in Doppler-derived valve effective orifice area (EOA) are real or due to artifact.', 'It has frequently been reported that the EOA may vary with transvalvular flow in patients with aortic stenosis. However, the explanation of the flow dependence of EOA remains controversial and some studies have suggested that the EOA estimated by Doppler-echocardiography (EOA(Dop)) may underestimate the actual EOA at low flow rates.', 'One bioprosthetic valve and three rigid orifices were tested in a mock flow circulation model over a wide range of flow rates. The EOA(Dop) was compared with reference values obtained using particle image velocimetry (EOA(PIV)).', 'There was excellent agreement between EOA(Dop) and EOA(PIV) (r2 = 0.94). For rigid orifices of 0.5 and 1.0 cm2, no significant change in the EOA was observed with increasing flow rate. However, substantial increases of both EOA(Dop) and EOA(PIV) were observed when stroke volume increased from 20 to 70 ml both in the 1.5 cm2 rigid orifice (+52% for EOA(Dop) and +54% for EOA(PIV)) and the bioprosthetic valve (+62% for EOA(Dop) and +63% for EOA(PIV)); such changes are explained either by the presence of unsteady effects at low flow rates and/or by an increase in valve leaflet opening.",
            "output": [
                "Are flow-dependent changes in Doppler-derived aortic valve effective orifice area real and not due to artifact?"
            ]
        },
        {
            "id": "task847-9fe0f9481bf94c199d9afe97c4270f80",
            "input": "The high number of nuclear cells (NCs) from hematopoietic progenitor cells-apheresis (HPC-A) requires cryopreservation in large volumes or at high NC concentrations. The effect of NC concentration during cryopreservation has yet to be examined.', 'In the experimental arm (n = 610, Protocol B), the first HPC-A sample from the patient was cryopreserved in two cryobags and subsequent collections in one cryobag, resulting in high NC concentrations (>100 x 10(6) NCs/mL) in most cases. The effect of NC concentrations at freezing in NC recovery after thawing and engraftment kinetics was analyzed and compared with a group of HPC-A cryopreserved at standard NC concentrations (n = 455, Protocol A).', 'The mean (SD) NC concentration at freezing was 78 (28) x 10(6) per mL (median, 82 x 10(6)/mL; range, 12 x 10(6)-156 x 10(6)/mL) and 183 (108) x 10(6) per mL (median, 156 x 10(6)/mL; range, 16 x 10(6)-678 x 10(6)/mL), for HPC-A cryopreserved according to Protocols A and B, respectively. The NC viabilities of the test vials and HPC-A components after thawing were 88 percent versus 85 percent and 85 percent versus 82 percent, and the cloning efficiency was 49 percent versus 33 percent for Protocols A and B, respectively (p < 0.001). Significant differences were not observed in the recovery of NCs. Days to neutrophil and platelet engraftment were not different between patients transplanted in the standard- (n = 143) or high-cell-concentration group (n = 238).",
            "output": [
                "Does cryopreservation of hematopoietic progenitor cells from apheresis at high cell concentrations impair the hematopoietic recovery after transplantation?"
            ]
        },
        {
            "id": "task847-77265f64261a4adcbae17ab2eb3bf3be",
            "input": "The extent to which tolerance acquired in one motion environment can be transferred to another has not been fully elucidated. This study compares three provocative motion stimuli and whether tolerance acquired from cross-coupled motion and torso rotation can be transferred to simulated aircraft motion.', \"There were 18 healthy subjects (9 men and 9 women), 18-44 yr of age, who were divided into 3 groups. Each group was exposed to the following desensitization procedure in a pseudo-random repeated measures design. In condition D1, subjects were exposed to 4 consecutive days of cross-coupling and on the 5th d they were exposed to simulated aircraft motion. In D2, subjects were exposed to 4 consecutive days of torso rotation and on the 5th day they were exposed to the simulated aircraft motion as in D1. In D3, subjects were exposed to 5 consecutive days of simulated aircraft motion. Based on Graybiel's diagnostic criteria, severity of motion sickness on the 1st and 5th day in D1, D2, and D3 were compared.\", 'Cross-coupled motion was the most provocative stimulus followed by torso rotation and simulated aircraft motion. Within each motion stimulus, there was evidence of desensitization (p < 0.001) within 4 d. There were no significant differences in the severity of motion sickness observed on the 5th day regardless of the desensitization stimuli.",
            "output": [
                "Does desensitization to strong vestibular stimuli improve tolerance to simulated aircraft motion?"
            ]
        },
        {
            "id": "task847-49030912e0784e66abe50276dd654a3b",
            "input": "To elucidate the retinal dysfunction and the molecular basis of posterior polymorphous corneal dystrophy (PPCD) associated with macular dystrophy, both inherited in a dominant manner through a three-generation family.', 'Ophthalmologic examinations including slit lamp examination, visual acuity tests, fundus visualization by scanning laser ophthalmoscopy, fluorescein angiography, color vision tests, electro-oculography, photopic and scotopic electroretinography (ERG) according to the International Society for Clinical Electrophysiology of Vision (ISCEV) protocols, and oscillatory potential (OP) recordings were conducted on affected family members. Corneal button from one affected patient was examined by transmission electron microscopy. All exons and intron-exon boundaries of the VSX1 and the COL8A2 genes were amplified by polymerase chain reaction and sequenced.', 'The presence of endothelial cells that have epithelial-like features with multiple layers, desmosomal junctions, and microvillous projections supports the diagnosis of PPCD. Sequence analysis indicated that the H244R variant in the VSX1 segregated with corneal and macular disease phenotypes in this family. Electrophysiologic studies indicated normal scotopic ERG findings, decreased amplitude of the photopic b-wave, photopic OP2 and OP3 barely recordable with a preserved OP4 amplitude, and variably decreased 30-Hz flicker amplitude.",
            "output": [
                "Is h244R VSX1 associated with selective cone ON bipolar cell dysfunction and macular degeneration in a PPCD family?"
            ]
        },
        {
            "id": "task847-06fece8c66954628ab06c3f776c1bbdc",
            "input": "To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary congenital glaucoma (PCG) worldwide.', 'Five intragenic single-nucleotide polymorphisms in CYP1B1-R48G, A119S, V432L, D449D, and N453S-were used to generate haplotype data from 138 Indian patients with PCG and 132 ethnically matched normal controls, which were then analyzed in conjunction with data from other populations. Maximum-likelihood estimates of haplotype frequencies were estimated from the genotype data. Subsets of patients and normal control subjects were also genotyped with respect to eight short tandem repeat (STR) markers around the CYP1B1 locus (D2S305, D2S165, D2S367, D2S2259, D2S391, D2S3337, D2S23678, and D2S286), to gain evolutionary insights.', 'Common mutations in CYP1B1 that are causal of PCG occurred on a uniform haplotype background among Indian patients, which is completely distinct from the modal haplotype background found among unaffected control subjects. Comparison of these data with data from other global regions reveals strong clustering of CYP1B1 mutations by geographic and haplotype backgrounds. The two distinct modal haplotypes found among Indian patients with PCG and control subjects are both ancient with ages of similar magnitudes, as indicated by large variances in the number of repeats at eight STR loci. Together with data from chimpanzee and normal control subjects from India and other global regions, it was possible to make a parsimonious reconstruction of the evolution of these haplotypes.",
            "output": [
                "Are globally , CYP1B1 mutations in primary congenital glaucoma strongly structured by geographic and haplotype backgrounds?"
            ]
        },
        {
            "id": "task847-96abc0c838cf43bbadec93027faad8c0",
            "input": "We investigated in vitro whether IL-1beta and TGF-beta1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion.', 'Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1beta and TGF-beta1 were evaluated using three primary and three metastatic pancreatic cancer cell lines.', 'Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1beta did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-beta1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines.",
            "output": [
                "Is pancreatic cancer cells invasiveness mainly affected by interleukin-1beta not by transforming growth factor-beta1?"
            ]
        },
        {
            "id": "task847-260e88cc6e2e411a8148744fdb9ba3cc",
            "input": "In recent years acute rejection has decreased to 10% to 20%. Therefore it is necessary to look for new endpoints in renal transplantation. Serum creatinine and changes in creatinine have been reported to be powerful predictors of long-term kidney transplant survival. Chronic renal allograft nephropathy is the primary cause of long-term graft failure but may appear at any stage in the evolution.', 'Data from 315 patients receiving cadaver donor renal transplants between February 1987 and March 2001 that functioned for 1 year were examined for the influence of demographic characteristics and transplant variables. Creatinine clearance was estimated using the Cockroft-Gault formula. Survival was assessed with the actuarial method. The multivariate analyses were performed using Cox proportional hazard models.', 'The 10-year graft survival showed a relative risk of 2.5 in the univariate analysis when there was more than 10% decrease in renal function at 3 months compared with nadir values. When the decrease was more than 25% of creatinine clearance at the third month, during the evolution and serum creatinine at 3 months introduced in the multivariate model, the latter was not significant, while the other variables had a RR of 4.4 and 10, respectively.",
            "output": [
                "Is evolution of the renal function a better predictor of long-term survival than serum creatinine?"
            ]
        },
        {
            "id": "task847-5346d5a6c9c645d3a67f9c00590a6cc2",
            "input": "To investigate the mechanism of platelet function caused by Lysophosphatidic acid (LPA), by observing the change of the L-arginine/nitric oxide synthase/nitric oxide (L-Arg/NOS/NO) pathway of platelet in rats.', 'LPA (10(-6), 10(-5) and 5x10(-5) mol/L) was administrated in rats and incubated for 30 and 60 minutes. The nitrite production was measured by Greiss assay; NOS activities and L-arginine transportation were detected by isotope tracer method and intracellular [Ca(2+)]i changes by fluorescent probe.', 'LPA increased NO release by 35% and 56%, after incubating for 30 and 60 minutes, respectively. LPA (10(-6), 10(-5)aand 5x10(-5) mol/L) enhanced the NO productions of platelets in a concentration-dependent manner (P<0.01). EC(50) was 17.8 micromol/L, and 95% CI was 13.3-24.2 micromol/L, involved in the physiological concentration of LPA in plasma (P<0.01). Simultaneously, different doses of LPA increased NOS activities and L-arginine uptake in a dose-dependent manner (P<0.01). In this study, LPA (50 micromol/L) increased the intracellular free calcium ion concentration ([Ca(2+)]i, P<0.01), after incubating for 30 and 60 minutes. Pre-treated with NOS inhibitor-L-NAME for 20 minutes, LPA obviously enhanced the effects by 20% and 32% respectively (P<0.01). On the contrary, pre-treated with L-arginine (200 micromol/L) for the same times obviously reduced the effects by 14% and 18% respectively (P<0.01).",
            "output": [
                "Does [ Lysophosphatidic acid activate L-arginine/nitric oxide pathway of platelets in rats ]?"
            ]
        },
        {
            "id": "task847-0e1b6f727bfc4945b3a3c79552a820b1",
            "input": "To investigate the expression level of genes located in chromosome 21 in the brain tissues of Down syndrome(DS).', 'An optimized semi-quantitative RT-PCR method was used to evaluate the expression levels of seven genes encoded in chromosome 21 in fetal cortex brain and cerebellum of DS and the control at the end of 20 weeks of gestation. B2M was used as internal reference to normalize cell loss.', 'The expression levels of 6 genes in cortex and cerebellum, including DYRK1A, SYNJ1, PCP4, C21orf5, C21orf2 and C21orf106, were comparable between DS and the control. ANA, a cell-cycle negative regulatory gene, was over-expressed dramatically in the cortex but not in the cerebellum of DS.",
            "output": [
                "Is [ Cell-cycle negative regulatory gene ANA over-expressed in the brain tissues of patients with Down syndrome ]?"
            ]
        },
        {
            "id": "task847-ff23d37cc71e4956a61217b7baa908bc",
            "input": "A cross-sectional community-based study was conducted among brothel-based sex workers of West Bengal, eastern India, to study the prevalence of HIV and associated risk factors.', 'Unlinked anonymous HIV testing was performed on 2076 sex workers. Of these, 558 were interviewed using a pre-tested questionnaire to study their risk factors.', 'Overall HIV sero-prevalence was 5.9%. All infections were HIV-1, except that four sex workers from Kolkata were infected with HIV-2. Surprisingly, HIV infection was much higher (12.5%) in younger sex workers (age < or =20 years) compared with older age groups (5.4%) (P=0.002; odds ratio 2.40, 95% CI: 1.29-4.38).",
            "output": [
                "Is young age a risk factor for HIV among female sex workers -- an experience from India?"
            ]
        },
        {
            "id": "task847-0449cb9c15b54e8eb8317940edb08353",
            "input": "Treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF)-blocking agents, including etanercept and infliximab, has resulted in reductions in the radiographic progression of RA. However, the exact mechanism by which this protection occurs has not been determined. In order to add to such knowledge, we investigated the effect of anti-TNF therapy on the expression of osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in synovial tissue.', \"The expression of OPG and RANKL in synovial biopsy specimens was evaluated by immunohistochemistry. Serial synovial biopsy specimens were obtained from 18 patients with RA, before and after treatment with etanercept (9 patients) or infliximab (9 patients). Biopsy specimens were evaluated by double-blind semiquantitative analysis and image analysis. The in vitro effect of TNF antagonists on the RANKL/OPG expression in osteoblasts and endothelial cells was evaluated by Western blotting. Statistical analysis was performed using Wilcoxon's signed rank test, followed by the Bonferroni correction for multiple comparisons of paired samples. The results of in vitro experiments were evaluated by one-way analysis of variance, with Tukey's post hoc test.\", 'Treatment with both infliximab and etanercept increased the expression of OPG in synovial tissue. After 8 weeks of treatment, neither infliximab nor etanercept influenced RANKL expression. In both groups of patients, the RANKL:OPG ratio decreased following therapy. In vitro, both of the TNF antagonists mimicked the in vivo effect, inducing a decrease in the RANKL:OPG ratio in TNF-primed osteoblasts and endothelial cells.",
            "output": [
                "Does anti-tumor necrosis factor therapy increase synovial osteoprotegerin expression in rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-2419efd715bd43379eab0889e15b6b78",
            "input": "Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT).', 'Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out.', 'Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival.",
            "output": [
                "Does postmastectomy radiotherapy reduce locoregional recurrence in elderly women with high-risk breast cancer?"
            ]
        },
        {
            "id": "task847-272bc2aeceba4919996faacf19770415",
            "input": "In HCV-related graft hepatitis, immunosuppression has been implicated in rapid progression to cirrhosis, a serious clinical issue. We investigated the effects of cyclosporine or tacrolimus on cell growth and collagen production by hepatic stellate cells (HSC), which play a role in hepatic fibrosis.', 'Cultured rat HSCs and human HSC-derived TWNT-4 cells were evaluated for proliferation, type I collagen, phosphorylation states of mitogen-activated protein kinases extracellular signal-regulated kinase 1/2; [MAPKs Erk1/2], c-Jun N-terminal kinase (JNK, p38), as well as the expression of collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) genes.', 'Cyclosporine suppressed cell growth and collagen production in a concentration-dependent manner. At clinically relevant concentrations of 0.125 micromol (150 ng/mL) cyclosporine significantly reduced collagen production per cell by more than 50%. Similarly, tacrolimus also reduced both collagen concentration and cell number; however, tacrolimus at a clinically relevant concentration of 12.5 nmol (10 ng/mL) did not significantly reduce collagen production. Treatment with cyclosporine reduced type I collagen and TIMP-1 expression and enhanced MMP-1 expression. Cyclosporine also inhibited phosphorylation strongly for JNK and p38, and weakly inhibited for Erk1/2.",
            "output": [
                "Does cyclosporine suppress cell growth and collagen production in hepatic stellate cells?"
            ]
        },
        {
            "id": "task847-4c8e4ec09ce241f3b5cd380e93c546a8",
            "input": "Increased oxidative stress is associated with coronary heart disease (CHD). We examined the association between plasma markers of oxidative stress and CHD in a cross-sectional sample of patients with diabetes and prospective CHD risk in a sample of men predominantly without diabetes.', 'Plasma total antioxidant status (TAOS) and the ratio of oxidized LDL (Ox-LDL) to LDL-cholesterol (LDL-C) were determined in a cross-section of 761 Caucasian individuals with diabetes (UDACS study). Plasma TAOS was also determined in 310 baseline samples from a 10-year prospective cohort of 3012 healthy males (NPHSII).', 'Within UDACS, males with CHD had lower mean (SD) plasma TAOS [no CHD, 43.4 (13.2)%; CHD, 40.3 (13.8)%; P = 0.04]. The prevalence of CHD was higher in the lowest compared with the upper quartiles (32.7% vs 19.7%; P = 0.004). We observed a significant association between plasma Ox-LDL:LDL-C and CHD status [no CHD vs CHD, 16.9 (3.1) vs 19.3 (5.0) units/mmol; P = 0.04], with the prevalence of CHD being higher among men in the upper compared with lower quartiles (18.4% vs 35.1%; P = 0.003). No association was observed in females. In NPHSII, TAOS was lower in those who developed CHD [35.1 (8.0)% vs 37.1 (7.9)%; P = 0.04]. The odds ratio for CHD in the lowest compared with the upper quartile was 1.91 (95% confidence interval, 0.99-3.70; P = 0.04). This remained unchanged after adjustment for classic risk factors.",
            "output": [
                "Are increased plasma markers of oxidative stress associated with coronary heart disease in males with diabetes mellitus and with 10-year risk in a prospective sample of males?"
            ]
        },
        {
            "id": "task847-c937e12210d54ed7821604f38c69cb2d",
            "input": "Transient lower esophageal sphincter relaxation is the main mechanism for gastroesophageal reflux. Although there is evidence that transient lower esophageal sphincter relaxations are neurally mediated, another school of thought is that transient lower esophageal sphincter relaxations result from gastric distention, which shortens the sphincter to the point where it opens and the pressure decreases. We assessed the relationship of transient lower esophageal sphincter relaxation to gastroesophageal junction opening in an unsedated human model.', 'Seven healthy volunteers (6 men and 1 woman, aged 18-53 years) were studied while they were sitting. Manometry was performed by using a sleeve catheter passed through 1 nostril. A 5.3-mm endoscope was placed through the other nostril to obtain a retroflexed view of the cardia. The biopsy channel was connected to a barostat to distend the stomach with air at 15 mm Hg for 30 minutes. Manometric and endoscopic video-recording times were synchronized but scored independently.', 'The transient lower esophageal sphincter relaxation onset invariably preceded gastroesophageal junction opening (median, 5.0 seconds; range, 0.5-20.7 seconds; P < .001). The transient lower esophageal sphincter relaxation nadir also typically occurred before gastroesophageal junction opening (median, 2.1 seconds; range, -4.2 to +19.5 seconds; P < .001). Once open, the gastroesophageal junction moved proximally for the duration of the transient lower esophageal sphincter relaxation. Termination of transient lower esophageal sphincter relaxations occurred about the time the time of gastroesophageal junction closure.",
            "output": [
                "Do transient lower esophageal sphincter relaxations result from passive opening of the cardia by gastric distention?"
            ]
        },
        {
            "id": "task847-a279c9d70829418da7a56a0c466e1ce3",
            "input": "Reg IV, a secreted protein and member of the Reg multigene family, is up-regulated in malignancies of the human gastrointestinal tract, including colorectal carcinoma (CRC). However, in vitro signal transduction pathway(s) utilized by Reg IV are not yet known.', 'To determine the signaling pathway(s) responsive to Reg IV, we examined the effects of purified recombinant human Reg IV (rhR4) on HCT116 and HT29 colon adenocarcinoma cells.', 'Addition of rhR4 to cultures led to a dose-dependent increase in cell number similar to that observed after treatment with epidermal growth factor (EGF). In addition, rhR4 treatment resulted in rapid phosphorylation of EGF receptor at Tyr992 and Tyr1068 and Akt at Thr308 and Ser473. Using luciferase reporter gene assays, we demonstrated that Reg IV signaling through EGF receptor and Akt results in increased activator protein-1 (AP-1) transcription factor activity. Real-time reverse-transcription polymerase chain reaction and Western blot analyses revealed quantitative increases in c-Jun, JunB, JunD, and FosB expression associated with increased AP-1 activity. Electrophoretic mobility shift assay further revealed significant increases in AP-1 binding activity in rhR4-treated cells, with increased supershift in the presence of antibodies to JunB, JunD, and FosB. Furthermore, rhR4 treatments led to the increased expression of Bcl-2, Bcl-XL, survivin, and matrilysin, genes associated with a poor prognosis in advanced CRC.",
            "output": [
                "Does reg IV activate the epidermal growth factor receptor/Akt/AP-1 signaling pathway in colon adenocarcinomas?"
            ]
        },
        {
            "id": "task847-6ba246185c3f409eb4384fae8b8fbf5a",
            "input": "The up-regulation of matrix metalloproteinases (MMPs) in the inflamed gut has mainly been associated with mucosal degradation and ulceration. However, their in vitro capacity to specifically cleave inflammatory mediators indicates that MMPs may have a profound immunoregulatory impact. We hypothesized that MMPs proteolytically modify intestinal epithelial chemokine signaling.', 'Interleukin-1beta-stimulated Caco-2 cells were exposed basolaterally to nanomolar concentrations of activated MMP-3 or cocultured with interleukin-1beta-stimulated, MMP-producing, colonic myofibroblasts (CCD-18co). The conditioned media were subjected to chemotaxis assays. In addition, epithelial cells from patients with colitis were examined by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry.', \"MMP-3 dose-dependently induced the neutrophil (up to 5-fold) but not monocyte chemoattractant capacity of Caco-2 cells. A similar Caco-2 chemotactic response was obtained in the Caco-2/CCD-18co cocultures. The principal mediator of these protease-related effects was identified as the potent neutrophil chemokine CXCL7 (neutrophil activating peptide 2), a proteolytic cleavage product of chemotactically inert platelet basic protein (PBP), not previously identified in the intestine. Antibodies against CXCL7 inhibited the MMP-induced chemotactic response by 84%, and PBP mRNA and protein were detected in stimulated Caco-2 but not in CCD-18co cells. Furthermore, PBP transcript and protein levels were low in the mucosa and in isolated epithelial cells from patients with Crohn's disease and from normal intestine but increased up to 13-fold in patients with ulcerative colitis.",
            "output": [
                "Do myofibroblast matrix metalloproteinases activate the neutrophil chemoattractant CXCL7 from intestinal epithelial cells?"
            ]
        },
        {
            "id": "task847-d602f6c6fde44f50b0334a440f2ca813",
            "input": "Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon.', 'A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24-28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies.', \"The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers.",
            "output": [
                "Is discontinuation of treatment of schizophrenic patients driven by poor symptom response : a pooled post-hoc analysis of four atypical antipsychotic drugs?"
            ]
        },
        {
            "id": "task847-b56ba5de82204f3f8131070dd80a92d4",
            "input": "The APOE genotype has a uniquely strong influence on the outcome of viral infection. The mechanism is unknown, although one possibility is direct inhibition of viral entry into cells.', 'We have examined the direct anti-infective activity of a peptide analogue of the receptor-binding region of apolipoprotein E (apoE) that is known as \"apoE dimer tandem repeat peptide\" (apoEdp) and has previously been shown to mimic some of the biological effects of apoE and that recently was shown to bind low-density lipoprotein receptor-related protein.', 'apoEdp has activity against herpes simplex virus types 1 and 2, human immunodeficiency virus, Pseudomonas aeruginosa, and Staphylococcus aureus; concentrations in the range of 1-20 micromol/L inhibit infection by 50%. These biological actions depend on adoption of an alpha -helical structure, as has been found for other biological effects of apoE peptides. The peptide interferes with the earliest stages of viral infection, preventing viral attachment and exerting a mild virucidal action. In addition, an N-terminal fragment of apoE that also contains this binding domain has antiviral activity.",
            "output": [
                "Does the receptor-binding region of human apolipoprotein E have direct anti-infective activity?"
            ]
        },
        {
            "id": "task847-247a05840cea4fd6b2377c3520a9da92",
            "input": "The ability to achieve significant donor engraftment without fully myeloablative conditioning has revolutionized allogeneic stem cell transplantation. These nonmyeloablative approaches may allow extension of this potentially curative modality to an increasing number of patients including those with non-malignant diseases. Although a number of regimens have been explored, the optimal means of conditioning has not been determined.', 'We previously demonstrated that rapamycin (RAPA) has the ability to promote T-cell tolerance even in the presence of costimulation. In the current study, we examine the ability of rapamycin or the calcineurin inhibitor cyclosporine A (CSA) to promote chimerism in a murine haploidentical bone marrow transplantation model. Mice were conditioned with 300 cGy and received either RAPA at 3 mg/kg/day IP, CSA at 20 mg/kg/day IP, or no immunosuppression starting on the day before the transplant and continued for 4 weeks.', 'There was no apparent toxicity, and animals maintained normal blood counts throughout. More importantly, long-term macrochimerism was observed only in the RAPA-treated group.",
            "output": [
                "Does low-dose radiation plus rapamycin promote long-term bone marrow chimerism?"
            ]
        },
        {
            "id": "task847-6a834e9db9044e88859616c916214c3b",
            "input": "Phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins and plays an important role in HDL metabolism. PLTP exists as a high-activity and a low-activity form in the circulation. In vitro studies have shown that apolipoprotein (apo) E is involved in maintaining PLTP in the active form, while the low-activity form is associated with apo AI. We have therefore investigated whether plasma apo AI, B and E concentrations are important determinants of plasma PLTP activity in type 2 diabetes, a condition associated with increased plasma PLTP activity.', 'Plasma PLTP activity was assayed by measuring the transfer of radiolabelled phosphatidylcholine from liposomes to HDL; apo AI and B by rate nephelometry and apo E by a 2-point turbidimetric assay.', 'Type 2 diabetic patients (n = 230) had higher PLTP activity than controls (n = 97) (2374 +/- 628 nmol/mL/h versus 1862 +/- 585 respectively, p < 0.01). They also had increased fasting triglyceride and low HDL. Plasma apo B (p < 0.01) and apo E (p < 0.05) were increased, whereas apo AI was reduced (p < 0.01). Univariate analysis showed that plasma PLTP activity correlated mainly with apolipoproteins AI and E. Stepwise regression analysis showed that apo E was the main determinant of plasma PLTP activity, accounting for 23% of its variability in the diabetic subjects and 8% in the controls respectively.",
            "output": [
                "Is plasma apolipoprotein E concentration an important determinant of phospholipid transfer protein activity in type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-8a7300e22fe047f7b09ad2e1ac668e1d",
            "input": "Left atrial (LA) enlargement is related to diastolic dysfunction and mitral regurgitation (MR), both of which are common in patients with hypertrophic cardiomyopathy (HCM). This study investigates the association between LA size and exercise capacity in patients with HCM.', 'All HCM patients who underwent a treadmill test with direct measurement of oxygen consumption (VO2) and a standard transthoracic echocardiography within 30 days in the years 2001-2003 were identified. Patients with significant comorbidities were excluded. Exercise capacity was defined as percentage of predicted peak VO2. Clinical and echocardiographic parameters were compared with those of a group of normal subjects.', \"Compared with normal subjects, HCM patients had increased left atrial (LA) volume index (36 vs 21 mL/m2; P < .0001) and mitral E/e' ratio (14 vs 9; P < .0001); 27% of the patients had at least moderate MR. LA volume index demonstrated borderline correlation with exercise capacity (r = -.20; P = .06) but was an independent predictor of exercise capacity in a multivariate linear analysis, together with body mass index, heart rate at rest, and left ventricular end-systolic diameter. Including the parameters E/e' ratio or moderate or severe MR did not add incremental value to the model.",
            "output": [
                "Is left atrial index a predictor of exercise capacity in patients with hypertrophic cardiomyopathy?"
            ]
        },
        {
            "id": "task847-818fb05222934f2bb4913a52f34c8fcc",
            "input": "Many trauma patients have been consuming alcohol at the time of injury. Although high concentrations of alcohol are correlated with poor outcome, few studies have examined the effects of low levels of alcohol. We examined the effects of low alcohol exposure after burn injury using a murine model.', 'Three- and 18-month-old mice were given ethanol or saline 30 minutes before a 15% total body surface area burn injury. Twenty-four hours after injury, cellular immune responses, including delayed-type hypersensitivity response and splenocyte proliferation were examined, along with production of interferon-gamma, interleukin (IL)-2, and IL-4.', 'Alcohol administration resulted in a significant increase in interferon-gamma in the aged, but not young, burn-injured mice. Likewise, slight increases in IL-2, IL-4, and the delayed-type hypersensitivity response were observed.",
            "output": [
                "Is a low blood ethanol level associated with improved cytokine production in aged mice after traumatic injury?"
            ]
        },
        {
            "id": "task847-d32ef42812f1409693286ae0d2c9f49a",
            "input": "Fluid resuscitation after uncontrolled hemorrhage might promote rebleeding and irreversible shock. Tranexamic acid is a procoagulant drug that limits blood loss after surgery of the hip, knee, and heart. We hypothesized that pretreatment with tranexamic acid reduces the rebleeding in uncontrolled hemorrhage and thereby allows safe administration of crystalloid fluid resuscitation.', \"A 120-minute intravenous infusion of 100 mL/kg of Ringer's solution was given to 24 pigs (mean weight, 20 kg) 10 minutes after lacerating the infrarenal aorta. The animals were randomized to receive an intravenous injection of 15 mg/kg of tranexamic acid or placebo just before starting the resuscitation. Rebleeding events were monitored by two ultrasonic probes positioned proximal and distal to the laceration.\", 'Tranexamic acid had no effect on the number of rebleeding events, bled volume, or mortality. The initial bleeding stopped within 4 minutes after the injury. The five animals that died suffered from 4.4 rebleeding events on average, which tripled the total blood loss, whereas the survivors had only 1.3 such events during fluid resuscitation (p < 0.02). At autopsy, death was associated with a larger total hemorrhage; the blood recovered from the abdomen weighed 1.4 kg (median) in nonsurvivors and 0.6 kg in survivors (p < 0.001), with the difference being attributable to rebleeding.",
            "output": [
                "Does tranexamic acid prevent rebleeding in an uncontrolled hemorrhage porcine model?"
            ]
        },
        {
            "id": "task847-2c12b356e6444ad7b4886f2af1ba8b9d",
            "input": "Different factors acting during pregnancy can cause non-morphological alterations of cells which are manifested later, in adulthood. We studied the effect of maternal alcohol consumption for one day in early pregnancy on the hormone content of immune cells in the adult rat.', 'Lactating dams were given 15% ethanol in the drinking water for 24 h on the 3rd day post partum, exposing their pups to ethanol in the breast milk. Some of the same dams had been successfully mated on the day of delivery, so that they were also 3 days pregnant on the treatment day, exposing embryos to alcohol on the third day of pregnancy. In 4 month old pups histamine and triiodothyronine (T(3)) content of citrate elicited peritoneal immune cells (lymphocytes, monocyte-macrophage-granulocyte group, mast cells) as well as thymic cells were determined by flow cytometry and confocal microscopy using specific antibodies.', 'Alcohol treatment during pregnancy decreased highly significantly the content of both hormones in peritoneal cells of the 4 month old adult animals while it was ineffective by breast feeding after birth. Thymic cells did not show any changes.",
            "output": [
                "Does alcohol consumption during gestation reduce the histamine and triiodothyronine content of rat immune cells?"
            ]
        },
        {
            "id": "task847-827d1349692f4db8afdacdacffa9b9c9",
            "input": "Tissue factor (TF) is a procoagulant that plays an important part in tumor angiogenesis. We sought to determine the role of preoperative serum TF levels in predicting clinical outcome in patients with ovarian cancer.', 'TF expression was determined by reverse transcriptase polymerase chain reaction in ovarian cell lines. Using enzyme-linked immunosorbent assay, we assessed preoperative serum TF levels in 98 women with invasive epithelial ovarian carcinoma, 30 with low malignant potential (LMP) tumors, 16 with benign tumors, and a separate validation group of 39 women with adnexal masses. Clinical information was gathered from chart review.', 'TF was expressed in four of the five ovarian cancer cell lines, but absent in the nontransformed cells. Ovarian cancer patients had a median preoperative serum TF level of 85.2 pg/mL, which was significantly higher than in those with LMP tumors (12.8 pg/mL; P < .01) and benign adnexal disease (30.7 pg/mL; P < .01). TF >or= 190 pg/mL was significantly associated with decreased patient survival (P < .01). After adjusting for other clinical variables in a multivariate Cox regression model, TF >or= 190 pg/mL was an independent prognostic factor (P < .01). Analysis of serum TF levels from the validation set confirmed that high TF (>or=190 pg/mL) was associated with a 3.4-fold increase in risk of death from disease (P = .02) and shorter survival (P = .01).",
            "output": [
                "Are preoperative serum tissue factor levels an independent prognostic factor in patients with ovarian carcinoma?"
            ]
        },
        {
            "id": "task847-d7cb6f157c154daea05fc0e0085709bf",
            "input": "Intravenous oxygen infusions have been introduced in complementary medicine for treatment of atherosclerosis and inflammatory diseases. As atherosclerosis and inflammation are causally related to oxidative stress and as intravenous supply with oxygen causes oxidative stress, it was suggested that the clinical success of intravenous oxygen therapy is biochemically based on an enhancement of endogenous antioxidative mechanisms. The anti-atherogenic enzyme paraoxonase-1 (PON1) is is part of this system.', 'To evaluate the effect of repeated intravenous oxygen infusions on serum PON1 activity.', 'A total of 45 patients were treated with intravenous oxygen. During treatment oxygen dosage was increased from 15 to 50 ml (1-2 ml/min). Before treatments 1 and 10 blood was obtained for measurement of PON1 activities. From 20 patients blood was additionally obtained after 20 days of treatment and 2 weeks post treatment. Serum PON1 activity was measured spectrophotometrically using the synthetic substrates paraoxon, phenylacetate, and p-nitrophenyl-acetate.', 'Using the substrate paraoxon PON1 activity significantly increased by 38% above basal levels 24 hours after intravenous oxygen infusion 9 (p < 0.001). Adverse effects were not observed.",
            "output": [
                "Does [ Intravenous oxygen therapy increase the activity of the antioxidative and antiatherogenic serum enzyme paraoxonase 1 ]?"
            ]
        },
        {
            "id": "task847-a0f7451e29d646e790629daef15d9051",
            "input": "To investigate whether the level of plasminogen activator (PA) activity assayed in gastrointestinal carcinomas and the \"morphologically normal tissues\" adjacent to them is associated with the degree of tumor progression.', 'Tumor and \"normal tissues\" were obtained from gastrointestinal surgical samples to assess urokinase-type (u-PA) and tissue-type plasminogen activator (t-PA) activities by radial caseinolytic assay and the expression of PA inhibitor-1 (PAI-1) by ELISA. We compared the PA system between the tumor and \"normal tissues\" and we investigated the existence of correlations between: (a) PA production in the tumor and \"normal tissues\", (b) different components of the PA system, and (c) PA system and the degree of tumor progression.', '(1) Total PA activity, u-PA activity and PAI-1 expression are significantly higher in tumor than in \"normal tissues\", whereas t-PA activity does not differ between them. (2) Total PA activity mainly correlates with u-PA activity in tumor tissues and similarly with u-PA and t-PA activities in \"normal tissues\". (3) There is a significant association between t-PA activity in tumor and \"normal tissues\" and the degree of tumor progression.",
            "output": [
                "Is tissue-type plasminogen activator activity in morphologically normal tissues adjacent to gastrointestinal carcinomas associated with the degree of tumor progression?"
            ]
        },
        {
            "id": "task847-e4ec4778da78431380c9cca0bac6df94",
            "input": "To assess if titration of sevoflurane using the bispectral index (BIS) monitor improves the early and intermediate recovery in geriatric outpatients undergoing brief urologic procedures under general anesthesia without muscle relaxants.', 'After a standardized induction with propofol and fentanyl, a laryngeal mask airway was inserted and sevoflurane was administered in combination with 60% nitrous oxide in oxygen for maintenance of anesthesia in spontaneously breathing outpatients. In the Control group (n = 25), sevoflurane and fentanyl were titrated according to standard clinical practice. In the BIS-directed group (n = 25), sevoflurane was titrated to maintain a BIS value between 50 and 60, and supplemental fentanyl, 25 mug iv boluses were administered to treat tachypnea. The intraoperative anesthetic and analgesic requirements, as well as the times to eye opening, removal of the laryngeal mask airway device, response to simple commands, orientation to person and place, and postanesthesia care unit discharge eligibility (fast-track score of 14) were assessed at specific time intervals.', 'The minimum alveolar concentration-hour of sevoflurane (0.25 +/- 0.15 and 0.31 +/- 0.2) and end-tidal concentrations of sevoflurane at the end of surgery (0.3 +/- 0.3 and 0.4 +/- 0.20%) did not differ significantly between the Control and BIS-directed groups, respectively. Although the percentage of patients requiring supplemental boluses of fentanyl was reduced in the BIS-directed group (16 vs 48%, P <0.05), the intraoperative BIS values and recovery times were similar in the two groups.",
            "output": [
                "Does bispectral index monitoring improve early recovery of geriatric outpatients undergoing brief surgical procedures?"
            ]
        },
        {
            "id": "task847-0e0fb5e44de740f09465cb2e6e0a0db7",
            "input": "Emerging clinical evidence suggests that gastroesophageal reflux disease is associated with pulmonary allograft dysfunction. In this study, we used a model of rat lung transplantation to test the hypothesis that chronic aspiration of gastric contents accelerates pulmonary allograft dysfunction.', 'We evaluated the effects of chronic aspiration on pulmonary isografts (strain F344) and pulmonary allografts (strain WKY to strain F344). Chronic aspiration consisted of 0.5 mL/kg of filtered gastric contents injected weekly into the left lung for 4 to 8 weeks beginning 1 week after transplantation. Seven days after the last aspiration, animals were killed, and grafts were evaluated grossly and by histologic and immunochemical analyses, including Masson trichrome staining for collagen and immunostaining for CD68+ and CD8+ cells. Serum cytokine concentrations were determined by bead-based immunoassays or enzyme-linked immunosorbent assay.', 'Allografts without aspiration (n = 12) demonstrated a relatively normal architecture with diffuse International Society for Heart and Lung Transplantation grade 3 acute rejection; occasional grade 4 rejection was noted. In contrast, allografts with chronic aspiration (n = 7) demonstrated severe grade 4 acute rejection with significant monocyte infiltration, fibrosis, and loss of normal alveolar anatomy. Grossly, 8 (67%) of 12 allografts without aspiration seemed to inflate and perfuse normally, whereas all allografts exposed to chronic aspiration were firm and shrunken, without the ability to ventilate (P = .013; Fisher exact test). Aspiration was associated with increases in graft-infiltrating macrophages and CD8+ T cells and higher levels of serum transforming growth factor beta.",
            "output": [
                "Does chronic aspiration of gastric fluid accelerate pulmonary allograft dysfunction in a rat model of lung transplantation?"
            ]
        },
        {
            "id": "task847-6b6f33afae4c4e0e99e1caa84122c74e",
            "input": "To study the effect of dexamethasone on postextubation stridor (PS) incidence and reintubation rate due to PS in a high-risk paediatric intensive care population.', 'All children aged between 4 wk and 6 y, who were intubated for at least 24 h and extubated between August 1999 and May 2002, were retrospectively included (n=60). Medical records of the included patients were studied; records of patients treated with dexamethasone prior to and following extubation (n=23) were compared with control patients who had not received prophylactic medication (n=37).', 'Nine patients in the control group developed significant postextubation stridor, necessitating nebulized epinephrine or glucocorticosteroids. In six of these children, reintubation as a result of postextubation stridor was indicated. None of the patients treated with dexamethasone developed severe postextubation stridor or required reintubation.",
            "output": [
                "Does dexamethasone reduce reintubation rate due to postextubation stridor in a high-risk paediatric population?"
            ]
        },
        {
            "id": "task847-09ece7764b3b4d1ba88ae27d0a43e07a",
            "input": "To determine whether burn-induced peroxynitrite production and expression of lung inducible nitric oxide synthase (iNOS), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, CXCR2, macrophage inflammatory protein (MIP)-2, and neutrophil chemokine (KC) are mediated by the c-Jun NH2-terminal kinase (JNK).', 'Prospective, experimental study.', 'Research laboratory at a university hospital.', 'Thermal injury models in the mice.', 'In experiment 1, specific pathogen-free C57/BL6 mice were subjected to 30% total body surface area third-degree burn over shaved back. At 0 hr, 2 hrs, 4 hrs, and 6 hrs after burn, lung tissues of those mice were harvested for JNK activity assay, AP-1 DNA-binding activity, and pJNK immunohistochemistry. In experiment 2, a specific JNK inhibitor, SP600125, was given (30 mg/kg intraperitoneally) to mice immediately postburn to suppress the JNK activity. At 8 hrs after burn, blood was assayed for the peroxynitrite-mediated dihydrorhodamine (DHR) 123 oxidation. Lung tissues were harvested for myeloperoxidase (MPO) determination, ICAM-1, VCAM-1, CXCR2, KC, MIP-2, interleukin-1beta, and interleukin-6 messenger RNA expression; iNOS immunohistochemical staining; and histologic studies. Pulmonary microvascular dysfunction was quantified by measuring the extravasations of Evans blue dye.', 'The JNK activity and AP-1 DNA-binding activity of lung tissue significantly increased to a peak at 2 hrs and 4 hrs, respectively, after thermal injury. Immunohistochemical study demonstrated that the increase of the pJNK was mostly from the bronchiole epithelial cells. This increase of MPO activity in lung, blood DHR 123 oxidation level, and lung permeability increased six-fold, nine-fold, and four-fold after burn. SP600125 administration obliterated the thermal injury-induced JNK activity, AP-1 DNA-binding activity, and iNOS expression in lung tissue. SP600125 treatment also significantly decreased MPO activity, blood DHR 123 oxidation, and lung permeability by 54%, 8%, and 47%, respectively, and markedly decreased the thermal injury-induced perivascular and interstitial inflammatory cell infiltration and septum edema. Furthermore, SP600125 abolished thermal injury-induced ICAM-1, VCAM-1, CXCR2, MIP-2, and KC but not interleukin-1beta and interleukin-6 messenger RNA levels of lung tissues.",
            "output": [
                "Do thermal injury-induced peroxynitrite production and pulmonary inducible nitric oxide synthase expression depend on JNK/AP-1 signaling?"
            ]
        },
        {
            "id": "task847-df0e9886a0cd4d519649dea217488928",
            "input": "Enhancing thrombus resolution may reduce the long-term complications of venous thrombosis. The aim of this study was to examine whether a sustained release of vascular endothelial growth factor (VEGF) would further improve thrombus recanalization.', 'Inferior caval vein thrombosis was induced in a cohort of 21 male Wistar rats. A plasmid encoding the human VEGF gene (phVEGF) was injected directly into thrombus (30 to 50 microg) and the muscle adjacent to the inferior vena cava (300 to 400 microg). A plasmid containing the gene encoding beta-galactosidase (pCMVbeta) was injected into the same sites of a separate cohort of rats to act as a control. Tissues were harvested after 1 and 2 weeks, and beta-galactosidase activity was measured to estimate transfection efficiency. Muscle and serum VEGF were measured by enzyme-inked immunosorbent assay. Thrombus size, recanalization, and organization were determined by computer-assisted image analysis.', 'The efficiency of control plasmid transfection into muscle was about 1%. No serum hVEGF was detected in phVEGF- or pCMVbeta-treated animals. Significantly raised levels of hVEGF (P < .01) were detected in the muscle injected with phVEGF after 2 weeks compared with control muscle. There was a significant reduction in thrombus size of 23% (P < .05) and 48% (P < .001) in phVEGF-treated animals compared with pCMVbeta-treated controls after 1 and 2 weeks, respectively. Thrombus recanalization was a significantly greater in the phVEGF-treated group after 2 weeks (mean 19% +/- 2% [SEM]) compared with controls (mean 13% +/- 2%, P < .01). There were no differences in the thrombus organization score.",
            "output": [
                "Does vascular endothelial growth factor naked DNA gene transfer enhance thrombus recanalization and resolution?"
            ]
        },
        {
            "id": "task847-ccdf30641142471f8ee3de4394579e43",
            "input": "Cancer is one of the devastating neovascular diseases that incapacitate so many people the world over. Recent reports from the National Cancer Institute indicate some significant gain therapy and cancer management as seen in the increase in the 5-year survival rate over the past two decades. Although near-perfect cure rate have been reported in the early-stage disease, these data reveal high recurrence rate and serious side effects including second malignancies and fatalities. Most of the currently used anticancer agents are only effective against proliferating cancer cells. Thus attention has been focused on potential anti-cancer agents capable of killing cancer cells independent of the cell cycle state, to ensure effective elimination of most cancer cells. The objective of this study was to test the chemosensitivity and potential mechanism of action of a novel cancer drug, CytoregR, in a panel of human cancer cells.', 'the study was performed using a series of bioassays including Trypan blue exclusion, MTS Growth inhibition, LDH-cytotoxicity, TUNEL-Terminal DNA fragmentation Apoptosis Assay, and the Caspase protease CPP32 activity assays.', 'CytoregR induced significant dose- and time-dependent inhibition of growth in all the cells; with significant differences in chemosensitivity (P < 0.05) between the target cells becoming more apparent at 48 hr exposure. CytoregR showed no significant effect on normal cells relative to the tumor cells. Growth inhibition in all the cells was due to induction of apoptosis at lower concentrations of cytoregR (> 1:300). CytoregR-induced caspase protease-3 (CPP32) activation significantly and positively correlated with apoptosis induction and growth inhibition; thus implicating CPP32 as the principal death pathway in cytoregR-induced apoptosis.",
            "output": [
                "Does cytoregR inhibit growth and proliferation of human adenocarcinoma cells via induction of apoptosis?"
            ]
        },
        {
            "id": "task847-a4e46a54fe474a36a1a0c1e75628a3fd",
            "input": "Severe pulmonary hypertension is a disabling disease with high mortality, characterized by pulmonary vascular remodeling and right heart hypertrophy. Using wild-type and homozygous endothelial nitric oxide synthase (NOS3(-/-)) knockout mice with pulmonary hypertension induced by chronic hypoxia and rats with monocrotaline-induced pulmonary hypertension, we examined whether the soluble guanylate cyclase (sGC) stimulator Bay41-2272 or the sGC activator Bay58-2667 could reverse pulmonary vascular remodeling.', 'Both Bay41-2272 and Bay58-2667 dose-dependently inhibited the pressor response of acute hypoxia in the isolated perfused lung system. When wild-type (NOS3(+/+)) or NOS3(-/-) mice were housed under 10% oxygen conditions for 21 or 35 days, both strains developed pulmonary hypertension, right heart hypertrophy, and pulmonary vascular remodeling, demonstrated by an increase in fully muscularized peripheral pulmonary arteries. Treatment of wild-type mice with the activator of sGC, Bay58-2667 (10 mg/kg per day), or the stimulator of sGC, Bay41-2272 (10 mg/kg per day), after full establishment of pulmonary hypertension from day 21 to day 35 significantly reduced pulmonary hypertension, right ventricular hypertrophy, and structural remodeling of the lung vasculature. In contrast, only minor efficacy of chronic sGC activator therapies was noted in NOS3(-/-) mice. In monocrotaline-injected rats with established severe pulmonary hypertension, both compounds significantly reversed hemodynamic and structural changes.",
            "output": [
                "Does activation of soluble guanylate cyclase reverse experimental pulmonary hypertension and vascular remodeling?"
            ]
        },
        {
            "id": "task847-4e54a8bfa8544195b7b64cd144175cd1",
            "input": "Small scale clinical trials suggested the feasibility and the efficacy of autologous myoblast transplantation to improve ventricular function after myocardial infarction. However, these trials were hampered by unexpected episodes of life-threatening ventricular tachyarrhythmias (VT). We investigated cardiac electrical stability after myoblast transplantation to the myocardium.', 'Seven days after coronary ligation, Wistar rats were randomized into 3 groups: a control group receiving no further treatment, a vehicle group injected with culture medium into the infarcted myocardium, and a myoblast group injected with autologous myoblasts. Holter monitoring did not discriminate the myoblast from the vehicle groups. Programmed Electrical Stimulation (PES) was performed to evaluate further a cardiac substrate for arrhythmia susceptibility. The occurrence of sustained VT during PES was similar in control and vehicle groups (5/17 and 4/19 rats, respectively; p=0.50). In contrast, 13/20 rats (65%) from the myoblast group showed at least one episode of sustained VT during PES (p<0.05 and p<0.005 versus control and vehicle groups). As a further control group, rats injected with autologous bone marrow mononuclear cells into the infarcted myocardium did not show increased susceptibility to PES.",
            "output": [
                "Does autologous myoblast transplantation after myocardial infarction increase the inducibility of ventricular arrhythmias?"
            ]
        },
        {
            "id": "task847-48c95751fe21457dac6e90ae021f36ee",
            "input": "Mucus accumulation in cystic fibrosis (CF) is involved in blockage of the distal small intestine. Because expression of mucin genes and mucus secretion can be increased by infection and previous work indicated that small intestinal bacterial overgrowth occurs in CF, we tested whether reduction of bacterial load by antibiotic treatment would reduce mucin gene expression and mucus accumulation in the CF mouse small intestine.', 'CF transmembrane conductance regulator null (cftr (tm1UNC)) and wild type littermates were treated with ciprofloxacin and metronidazole for 3 weeks. Muc2 and Muc3 gene expression were measured by quantitative reverse-transcriptase polymerase chain reaction. Periodic acid Schiff (PAS) staining and morphometry were used to measure the size of mucus droplets within goblet cells and dilation of the intestinal crypt lumen, as estimates of mucus secretion and accumulation.', 'Antibiotic treatment did not significantly affect Muc2 and Muc3 gene expression in CF mice. In untreated CF mice, the crypt lumen was almost sevenfold wider than wild type. Antibiotic treatment of CF mice reduced the intensity of PAS crypt lumen staining, and the lumen width was decreased by approximately 25%. The area occupied by PAS-positive material in goblet cells was significantly greater in tissues from antibiotic treated mice.",
            "output": [
                "Does eradication of small intestinal bacterial overgrowth in the cystic fibrosis mouse reduce mucus accumulation?"
            ]
        },
        {
            "id": "task847-29ec986cc44b419ca597f5784ddacca2",
            "input": "The intestine adapts morphologically or functionally in response to environmental stimuli. Dietary lipids modify brush border membrane (BBM) permeability and nutrient transporter activities. Gangliosides (GANG) are glycolipids in human milk that are present only in low amounts in infant formula. Exogenous GANG are incorporated into cell membranes and increase their permeability. The objective of this study was to determine whether feeding a GANG-enriched diet alters in vitro intestinal lipid absorption.', 'Weanling rats were fed either (1) GANG-enriched diet; (2) diet enriched with polyunsaturated long-chain fatty acids; or (3) isocaloric control diet for 2 weeks, after which in vitro intestinal lipid uptake was measured.', 'Feeding GANG did not alter weight gain or intestinal morphology. Enhanced uptake of stearic acid (18:0) in the ileum and stearic and linoleic acid (18:2) in the jejunum was not associated with a change in the abundance of the ileal lipid binding protein (ILBP), the intestinal fatty acid binding protein (I-FABP), or the liver fatty acid binding protein (L-FABP).",
            "output": [
                "Do dietary gangliosides enhance in vitro lipid uptake in weanling rats?"
            ]
        },
        {
            "id": "task847-54c9b7a4e011415d800d2c48dbc08eb6",
            "input": "Detection of small (10-20%) increases in lung water may be relevant to detect incipient pulmonary edema but no clinically usable method has demonstrated this capability to date.', 'In six pigs weighing 28 to 35 kg, we performed 18 determinations of extravascular lung water (EVLW; transpulmonary thermodilution method) before and immediately after the intratracheal introduction of 50 mL of saline solution. Six determinations were performed in normal lung and 12 in edematous lung.', 'In normal lung, the mean of EVLW increased from 245 +/- 18 mL to 288 +/- 19 mL (p < 0.001) after the intratracheal introduction of 50 mL of saline solution; therefore, 43 of the 50 mL (84%) were detected (range, 37-48 mL). In edematous lung, the EVLW increased from 491 +/- 106 mL to 530 +/- 108 mL after the introduction of 50 mL of saline solution; therefore, 39 of the 50 mL (77%) were detected (range, 15-67 mL).",
            "output": [
                "Are small increases in extravascular lung water accurately detected by transpulmonary thermodilution?"
            ]
        },
        {
            "id": "task847-67e034c662e04cc484a63962d299cede",
            "input": "The plasma activity of phospholipid transfer protein (PLTP), which has putative pro- and anti-atherogenic roles in lipoprotein metabolism, is increased in type 2 diabetes mellitus. We analysed the relationship between carotid artery intima-media thickness (IMT), an established marker of atherosclerosis, and PLTP activity in diabetic patients and control subjects.', 'The IMT (mean of three segments in both carotid arteries by ultrasonography), clinical variables, plasma PLTP activity (phospholipid vesicle-HDL system), lipoproteins, C-reactive protein and insulin were measured in 87 non-smoking men and women, who had type 2 diabetes mellitus, no cardiovascular disease, and were not on insulin or lipid-lowering medication, and in 83 age-matched control subjects.', 'In diabetic patients, carotid IMT (p=0.02), pulse pressure (p=0.003), plasma PLTP activity (p<0.001), triglycerides (p=0.01), C-reactive protein (p<0.01) and insulin (p<0.001) were higher, whereas HDL cholesterol was lower (p<0.001) than in control subjects. Multiple stepwise linear regression analysis demonstrated that in type 2 diabetic patients IMT was independently associated with age (p<0.001), sex (p=0.001), pulse pressure (p=0.003), plasma PLTP activity (p=0.03) and HDL cholesterol (p=0.03), but not with very low density lipoprotein+LDL cholesterol, triglycerides, C-reactive protein and insulin (all p>0.20). The relationship between plasma PLTP activity and IMT was not significant in control subjects.",
            "output": [
                "Is elevated plasma phospholipid transfer protein activity a determinant of carotid intima-media thickness in type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-3b3b0b6f5e3149f8aa4deb4a4ca18004",
            "input": "Results of many studies show that apolipoprotein B (apo B) is a better marker of risk of vascular disease than other lipid markers including LDL and HDL-cholesterol and triglycerides. We investigated the association between two infectious agents: C. pneumoniae and H. pylori, known to have an atherogenic effect, and apo B, to evaluate the effects of chronic infections on apo B levels.', 'The study group consisted of 257 patients in whom diagnostic coronary angiography was performed. C. pneumoniae IgG and IgM and H. pylori IgG and IgA antibodies were measured by enzyme-linked immunosorbent assay and apo B levels were measured by the nephelometry method. Established risk factors of atherosclerosis were recorded. Of 257 patients recruited, 104 had normal vessels, 88 had 3 or more vessels obstructed and 65 had ectatic vessels without atherosclerosis. Mean apo B concentration was significantly higher in C. pneumoniae IgG and IgM positive healthy subjects compared with C. pneumoniae negatives (0.954 vs. 0.722 and 0.973 vs. 0.851, p < 0.001 and p = 0.007, respectively). Apo B levels were significantly higher in severe atherosclerotic patients (0.985 +/- 0.234 g/l) compared with control subjects (0.892 +/- 0.244 g/l) (p = 0.008), but the difference was not significant in ectatic subjects (0.946 +/- 0.272 g/l) when compared with controls (p = 0.18). Apo B levels were higher but not statistically significant in H. pylori antibody positive cases when compared with negatives.",
            "output": [
                "Is infection with Chlamydia pneumoniae but not Helicobacter pylori related to elevated apolipoprotein B levels?"
            ]
        },
        {
            "id": "task847-94147c838f0e4c77adf3d7db32603db1",
            "input": "Loss of PTEN expression is one of the most prevalent and earliest molecular abnormalities associated with endometrial carcinogenesis. Given that PTEN is often absent and telomerase is overexpressed by endometrial cancers, we hypothesize that PTEN signaling is important in telomerase regulation.', 'PTEN expression was reconstituted in the PTEN-null Ishikawa endometrial cancer cells by adenovirus-mediated gene transduction. Cell proliferation was evaluated 12-96 h after infection. Western blot analysis was performed to assess PTEN status and phosphorylated Akt expression. Telomerase activity was determined by the telomeric repeat amplification protocol (TRAP) assay. hTERT mRNA levels were assessed by real-time RT-PCR. Ishikawa cells were also treated with LY294002, a PI3-kinase inhibitor.', 'Infection of Ishikawa cells by replication-defective recombinant adenovirus expressing wild-type PTEN, but not control adenovirus or adenovirus expressing lipid phosphatase defective PTEN GE mutant, inhibited constitutive Akt activation and suppressed proliferation of Ishikawa cells. Infection by wild-type PTEN adenovirus, but not control adenovirus, inhibited telomerase activity 24 h after infection. This inhibition of telomerase activity was parallel to decreased hTERT mRNA levels. LY294002 treatment resulted in dose-dependent inhibition of Akt activation and cellular proliferation. LY294002 suppressed telomerase activity and decreased hTERT transcript levels in a dose-dependent manner.",
            "output": [
                "Does the PTEN tumor suppressor inhibit telomerase activity in endometrial cancer cells by decreasing hTERT mRNA levels?"
            ]
        },
        {
            "id": "task847-ee9ecb12a1e5437a853422297546d937",
            "input": "The aim of this in vitro study was to evaluate the cytotoxicity of resin-modified glass-ionomer lining cements submitted to different curing regimes and applied to an immortalized odontoblast-cell line (MDPC-23).', \"Forty round-shaped specimens of each experimental material (Fuji Lining LC and Vitrebond) were prepared. They were light-cured for the manufacturers' recommended time (MRT = 30 s), under-cured (0.5 MRT = 15 s), over-cured (1.5 MRT = 45 s) or allowed to dark cure (0 MRT). Sterilized filter papers soaked with either 5 microL of PBS or HEMA were used as negative and positive control, respectively. After placing the specimens individually in wells of 24-well dishes, odontoblast-like cells MDPC-23 (30,000 cells/cm2) were plated in each well and incubated for 72 h in a humidified incubator at 37 degrees C with 5% CO2 and 95% air. The cytotoxicity was evaluated by the cell metabolism (MTT assay) and cell morphology (SEM).\", 'Fuji Lining LC was less cytotoxic than Vitrebond (p < 0.05) in all the experimental conditions. However, the cytotoxicity of Fuji Lining LC was noticeably increased in the absence of light-curing while the same was not observed for Vitrebond. The length of light-curing (15, 30 or 45 s) did not influence the toxicity of both lining materials when they were applied on the odontoblast-cell line MDPC-23.",
            "output": [
                "Does effect of curing regime on the cytotoxicity of resin-modified glass-ionomer lining cement applied to an odontoblast-cell line?"
            ]
        },
        {
            "id": "task847-6654477092eb46df822f41c631e5698e",
            "input": "Nitric oxide (NO) is a destructive mediator produced by activated chondrocytes. The aim of the present study was to investigate the effect of disease-modifying anti-rheumatic drugs (DMARDs) on interleukin-1beta (IL-1beta)-induced NO production in chondrocyte cultures, and in human osteoarthritic cartilage.', 'Aurothiomalate, hydroxychloroquine, methotrexate and leflunomide inhibited IL-1beta-induced inducible NO synthase (iNOS) expression and NO production in immortalized H4 chondrocytes, while penicillamine and sulfasalazine had no effect. This can be explained by the fact that the four effective DMARDs also suppressed IL-1beta-induced activation of nuclear factor kappa B (NF-kappaB), which is a crucial transcription factor for iNOS. Aurothiomalate and hydroxychloroquine also inhibited IL-1beta-induced NO production in OA cartilage whereas methotrexate and leflunomide had no effect.",
            "output": [
                "Do aurothiomalate and hydroxychloroquine inhibit nitric oxide production in chondrocytes and in human osteoarthritic cartilage?"
            ]
        },
        {
            "id": "task847-4f552521dbc9489aacada129b2959b57",
            "input": "Mice heterozygous for the Del1 transgene locus with a short deletion mutation in the type II collagen gene develop early-onset degenerative changes in the knee joints that progress to end-stage osteoarthritis by the age of 12-15 months. This study focuses on the expression and distribution of syndecan-1, a cell-surface heparan sulfate proteoglycan, during the development of osteoarthritic cartilage degeneration, to better understand its role in this disease.', 'Northern analyses of total RNA extracted from knee joints of transgenic Del1 mice and their nontransgenic controls were used to monitor changes in syndecan-1 mRNA levels during development, growth, ageing, and cartilage degeneration. Immunohistochemistry was used to study the distribution of syndecan-1 in the knee joints at different stages of cartilage degeneration.', 'Syndecan-1 mRNA was present in knee joints throughout life, with the highest mRNA levels in ageing knee joints. In Del1 mice, a transient upregulation of syndecan-1 mRNA synthesis was observed at the age of 6 months coinciding with early stages of cartilage degeneration and a period of attempted repair. Immunostaining for syndecan-1 was most intense in chondrocytes of superficial and intermediate zones of articular cartilage adjacent to defect areas. Chondrocyte clusters also stained strongly for syndecan-1.",
            "output": [
                "Is syndecan-1 expression upregulated in degenerating articular cartilage in a transgenic mouse model for osteoarthritis?"
            ]
        },
        {
            "id": "task847-ea7d8cf6693b4122949532d0445bf82c",
            "input": "Otsuka Long-Evans Tokushima Fatty (OLETF) rats genetically develop diabetes which is associated with hypertension. In preliminary studies, urinary excretions of L-PGDS (lipocaline-type prostaglandin D synthase) increase before diabetic nephropathy obviously develops, and this may predict progression of renal injury following diabetes. In the present study, we attempted to define whether urinary excretions of L-PGDS behave as the predictor of development of diabetic nephropathy in OLETF rats.', 'We investigated alterations of urinary L-PGDS excretions during the establishment of diabetes and assessed the relationship between the L-PGDS excretions and renal function in OLETF rats. Furthermore, we treated OLETF rats with troglitazone and analysed the effects on L-PGDS metabolisms. Urinary L-PGDS was measured by immunoenzyme assay and the occurrence of L-PGDS and its mRNA in the kidney was assessed by immunohistochemistry and a PCR method.', 'Urinary excretions of L-PGDS were significantly higher in OLETF rats than non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. The excretions age-dependently increased in OLETF and this increase appeared to be due to increased glomerular permeability to L-PGDS. Messenger RNA and antigenicity of L-PGDS were demonstrated in renal tissue; however, the de novo synthesis of L-PGDS mRNA seemingly contributed to urinary L-PGDS excretions much less than glomerular filtration. Multiple regression analysis revealed that urinary L-PGDS was determined by urinary protein excretions, and not by high blood pressure per se. Conversely, urinary proteinuria in the established diabetic nephropathy was predicted by urinary L-PGDS excretions in the early stage of diabetes.",
            "output": [
                "Do urinary excretions of lipocalin-type prostaglandin D2 synthase predict the development of proteinuria and renal injury in OLETF rats?"
            ]
        },
        {
            "id": "task847-a0ea41263a0840c88f9cd0535afbf8e9",
            "input": "Mutation of the Chx10 homeobox gene in mice and humans causes congenital blindness and microphthalmia (small eyes). This study used Chx10-/- (ocular retardation) mice to investigate how lack of Chx10 affects progenitor/stem cell behavior in the retina and ciliary epithelium (CE).', 'The distribution of mitotic retinal progenitor cells (RPCs) during embryonic development was analyzed using phosphohistone 3 (H3)-labeling. DNA flow cytometry was used to measure DNA content. The distribution and phenotype of dividing cells in the postnatal retina and CE was analyzed by incorporation of the thymidine analogue BrdU and immunohistochemistry.', 'The Chx10-/- embryonic retina maintained a constantly sized population of mitotic RPCs during development, causing the mitotic index to increase markedly over time compared with the wild type. Also, the proportion of cells in the G1 phase of the cell cycle was increased compared with the wild type. Of interest, division of RPC-like cells with neurogenic properties persisted in the adult Chx10-/- retina. Colabeling for BrdU and the neural progenitor marker nestin or the neuronal markers beta3-tubulin, syntaxin, and VC1.1 showed that new amacrine-like neurons developed in the adult central retina. By contrast, cells with these characteristics were not observed in the mature wild-type retina. In the mature CE, BrdU-positive cells were observed in both wild-type and Chx10-/- mice. However, neurogenesis from this cell population was not evident.",
            "output": [
                "Does absence of chx10 cause neural progenitors to persist in the adult retina?"
            ]
        },
        {
            "id": "task847-703d03f250af4c37915bf6986126a6a7",
            "input": "Although chest radiography is quick and inexpensive, previous research suggests that it is often misleading in emergency department (ED) patients with decompensated heart failure, resulting in misdiagnosis and inappropriate treatment. This study determines the rate of negative chest radiography results in patients found to have disease and the potential contribution of negative findings to a diagnosis discordant with heart failure by an emergency physician.', 'We used data from the Acute Decompensated Heart Failure National Registry (ADHERE), a registry of patients with a primary hospital discharge diagnosis of heart failure. We compared initial ED admitting diagnosis to the criterion standard of a hospital discharge diagnosis of heart failure and related these to radiographic findings of heart failure (interstitial edema, pulmonary edema, or vascular congestion, as determined by a staff radiologist) for patients first treated in the ED. The proportion of patients with a non-heart failure ED diagnosis and the diagnostic sensitivity of radiographic findings of heart failure are calculated.', 'There were 85,376 patients with chest radiograph results and an ED admitting diagnosis. Overall, there were 15,937 patients with no signs of congestion on ED chest radiography, giving a negative rate of 18.7% (95% confidence interval [CI] 18.4% to 18.9%). The proportion of patients with an ED non-heart failure admitting diagnosis was higher in patients with a negative chest radiograph result (23.3%; 95% CI 22.6% to 23.9%) than in patients with a positive chest radiograph result (13.0%; 95% CI 12.7% to 13.2%).",
            "output": [
                "Does prevalence of negative chest radiography result in the emergency department patient with decompensated heart failure?"
            ]
        },
        {
            "id": "task847-9f573fba9cc149cf8f03a06b78cbef0c",
            "input": "Thrombin is generated in significant quantities during cardiopulmonary bypass and mediates adverse events, such as platelet aggregation and proinflammatory responses, through activation of the high-affinity thrombin receptor protease-activated receptor 1, which is expressed on platelets and endothelium. Thus antagonism of protease-activated receptor 1 might have broad therapeutic significance. Aprotinin, used clinically to reduce transfusion requirements and the inflammatory response to bypass, has been shown to inhibit protease-activated receptor 1 on platelets in vitro and in vivo. Here we have examined whether aprotinin inhibits endothelial protease-activated receptor 1 activation and resulting proinflammatory responses induced by thrombin.', 'Protease-activated receptor 1 expression and function were examined in cultured human umbilical vein endothelial cells after treatment with alpha-thrombin at 0.02 to 0.15 U/mL in the presence or absence of aprotinin (200-1600 kallikrein inhibitory units/mL). Protease-activated receptor 1 activation was assessed by using an antibody, SPAN-12, which detects only the unactivated receptor, and thrombin-mediated calcium fluxes. Other thrombin-dependent inflammatory pathways investigated were phosphorylation of the p42/44 mitogen-activated protein kinase, upregulation of the early growth response 1 transcription factor, and production of the proinflammatory cytokine interleukin 6.', 'Pretreatment of cultured endothelial cells with aprotinin significantly spared protease-activated receptor 1 receptor cleavage (P < .0001) and abrogated calcium fluxes caused by thrombin. Aprotinin inhibited intracellular signaling through p42/44 mitogen-activated protein kinase (P < .05) and early growth response 1 transcription factor (P < .05), as well as interleukin 6 secretion caused by thrombin (P < .005).",
            "output": [
                "Does aprotinin inhibit proinflammatory activation of endothelial cells by thrombin through the protease-activated receptor 1?"
            ]
        },
        {
            "id": "task847-e8d4cf270e064cf3b94e6f85b9c25990",
            "input": "We reviewed our experience with preoperative chemoradiotherapy in patients with adenocarcinoma of the distal esophagus and pretreatment endoscopic ultrasonography-identified celiac adenopathy.', 'One hundred eighty-six patients with adenocarcinoma of the distal esophagus were staged with endoscopic ultrasonography before treatment from 1997 through 2004. All patients were treated with concurrent chemoradiotherapy (CRT group) and surgical intervention or induction chemotherapy followed by concurrent chemoradiotherapy (C-->CRT group) and surgical intervention. Survival analysis (excluding operative mortality) evaluated various pretreatment factors.', 'Multivariable Cox regression analysis showed that pretreatment endoscopic ultrasonography-identified celiac adenopathy was a significant predictor of decreased long-term survival (P = .03). Median and 3-year survivals were 49 months and 54% in the endoscopic ultrasonography-identified cN0 M0 group (n = 65), 45 months and 56% in the endoscopic ultrasonography-identified cN1 M0 group (n = 96), and 19 months and 12% in the endoscopic ultrasonography-identified celiac adenopathy (cM1a) group (n = 18; P = .03). Increased systemic relapse was noted in the endoscopic ultrasonography-identified cM1a group (44% vs 22%, P = .07). The only factor associated with increased survival in the endoscopic ultrasonography-identified cM1a group (27 vs 15 months, P = .02) was the addition of induction chemotherapy before concurrent chemoradiotherapy and surgical intervention.",
            "output": [
                "Does endoscopic ultrasonography-identified celiac adenopathy remain a poor prognostic factor despite preoperative chemoradiotherapy in esophageal adenocarcinoma?"
            ]
        },
        {
            "id": "task847-6bdb339c8ae742b79b20256d55f7f7a8",
            "input": "Elevated homocysteine levels during embryonic development can result in neural tube and cardiovascular defects. The mechanisms that underlie the toxic effect of homocysteine are largely unknown.', 'We cultured mouse neural tube explants to study the effects of homocysteine on the migratory behavior of neural crest cells and on the levels of the gap junction protein Connexin43 (Cx43) and the actin- and Cx43-interacting protein ZO-1.', 'Homocysteine exposure resulted in a significantly augmented maximal migration distance (MMD). The level of Cx43 immunolabeling was 2 times higher in the cytoplasm and cell protrusions of neural crest cells in homocysteine-treated cultures than in control cultures. Furthermore, colocalization of Cx43 and ZO-1 was increased in neural crest cell protrusions by this treatment.",
            "output": [
                "Are connexin43 levels increased in mouse neural crest cells exposed to homocysteine?"
            ]
        },
        {
            "id": "task847-c8d49c27281c4edb881c5ed21794e309",
            "input": "Circulatory shock results in hypoxia/reoxygenation processes that lead to the release of reactive oxygen species, endothelial injury, and multiple organ failure. Previous data suggest that beta2-adrenergic agonists prevent endothelial dysfunction. The study aimed at determining whether the beta2-adrenergic agonist formoterol protects endothelial cells against hypoxia/reoxygenation injury in vitro.', 'Prospective controlled trial.', 'University hospital research laboratory.', 'Cultured human umbilical vein endothelial cells (HUVECs).', \"Confluent HUVECs were sealed in a flow-through chamber mounted on an inverted microscope and perfused with a constant flow of Krebs medium. After 1 hr of equilibration, HUVECs underwent 2 hrs of hypoxia and 1 hr of reoxygenation. Cell death at the end of reoxygenation and reactive oxygen species formation were assessed with fluorescent probes propidium iodide and 2',7'-dichlorodihydrofluorescein diacetate, respectively. The effects of the beta2-adrenergic agonist formoterol, the beta2-adrenergic antagonist ICI 118,551 and the nitric oxide synthase inhibitor L-NNA were investigated. Statistical analysis was performed with analysis of variance followed by post hoc Fisher's test.\", 'Hypoxia/reoxygenation increased cell death (hypoxia/reoxygenation 29 +/- 4% vs. control 1 +/- 5%, p < .05) and endothelial reactive oxygen species production (hypoxia/reoxygenation 126 +/- 4% vs. control 108 +/- 4%, p < .05). Formoterol reduced cell death in a concentration-dependent manner (EC95 = 10 mol/L) and reduced endothelial reactive oxygen species production (hypoxia/reoxygenation + formoterol EC95 109 +/- 4% vs. hypoxia/reoxygenation 126 +/- 4%, p < .05). When added to formoterol EC95, ICI 118,551 and L-NNA abolished the formoterol-induced cell protection and reduced reactive oxygen species production.",
            "output": [
                "Does beta2-adrenergic agonist protect human endothelial cells from hypoxia/reoxygenation injury in vitro?"
            ]
        },
        {
            "id": "task847-b7a1e62922c4429c84afca77ff6d10c9",
            "input": "We analyzed the involvement of thromboxane (TX) A2/prostaglandin (PG) H2 (TP) receptor in ischemia-induced neovascularization in mice.', 'Unilateral hindlimb ischemia was induced by right femoral artery ligature in male C57BL/6J mice (n=7 per group). Animals were then treated with or without TP receptor antagonist (S18886, 5 or 10 mg/kg per day; ramatroban, 10 mg/kg per day) or aspirin (30 mg/kg per day) in drinking water for 21 days. Hindlimb ischemia raised plasma level of TXB2, the stable metabolite of TXA2, by 4.7-fold. This increase was blocked by aspirin treatment whereas S18886 (5 or 10 mg/kg per day) had no effect. However, neither S 18886 nor aspirin affected postischemic neovascularization. We next assessed the putative involvement of TXA2 signaling in angiotensin II (Ang II) proangiogenic pathway. Ang II (0.3 mg/kg per day) enhanced TXB2 plasma levels by 2.6-fold over that of control (P<0.01). Ang II-induced TXB2 upregulation was reduced by cotreatment with Ang II type I receptor antagonist (candesartan, 20 mg/kg per day). Angiographic score, capillary number, and foot perfusion were improved by 1.7-, 1.7-, and 1.4-fold, respectively, in Ang II-treated mice compared with controls (P<0.05). Ang II proangiogenic effect was associated with a 1.6-fold increase in VEGF-A protein content (P<0.05) and a 1.4-fold increase in the number of Mac-3-positive cells (ie, macrophages) in ischemic areas (P<0.05). Interestingly, treatments with TP receptor antagonists or aspirin hampered the proangiogenic effects of Ang II.",
            "output": [
                "Does thromboxane A2/prostaglandin H2 receptor activation mediate angiotensin II-induced postischemic neovascularization?"
            ]
        },
        {
            "id": "task847-9f4c1296556d410ea050f89a60f91fac",
            "input": "To determine whether tissue factor (TF) contributes to the progression of atherosclerotic lesions in mice.', 'We determined the effect of a 50% reduction of TF levels in all cells on atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice. No differences were observed in the extent of atherosclerosis in apoE(-/-)/TF(+/+) and apoE(-/-)/TF(+/-) mice fed regular chow for 34 weeks. Atherosclerosis could not be analyzed in apoE(-/-) mice expressing low levels of TF because of premature death of these mice. Macrophages are a major source of TF in atherosclerotic plaques. Therefore, in a second series of experiments, we investigated the effect on atherosclerosis of selectively reducing hematopoietic cell-derived TF by transplanting bone marrow from mice expressing low levels of TF into low-density lipoprotein receptor deficient (LDLR(-/-)) mice. Atherosclerosis within the arterial tree and aortic root were similar in LDLR(-/-) mice with low-TF bone marrow compared with control bone marrow (TF(+/+) or TF(+/-)) after 4 and 16 weeks on an atherogenic diet. Furthermore, the cellular composition of the aortic root lesions was similar between the 2 groups.",
            "output": [
                "Is atherosclerosis in mice affected by a reduction in tissue factor expression?"
            ]
        },
        {
            "id": "task847-5d03363101a14817a587ad95c6ee2b94",
            "input": "The neurochemical effects produced by acute administration of 3,4-methylenedioxymethamphetamine (MDMA) on the monoaminergic systems in the brain are well documented; however, there has been little consideration of the potential effects of MDMA on other neurotransmitter systems.', 'The present study was designed to investigate the acute effect of MDMA on cholinergic neurons by measuring acetylcholine (ACh) release in the medial prefrontal cortex (PFC) and dorsal hippocampus, terminal regions of cholinergic projection neurons originating in the basal forebrain.', 'In vivo microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ED) were used to assess the effects of MDMA on the extracellular concentration of ACh in the PFC and dorsal hippocampus of the rat.', 'The systemic administration of MDMA (3-20 mg/kg, i.p.) resulted in an increased extracellular concentration of ACh in the PFC and dorsal hippocampus. Reverse dialysis of MDMA (100 microM) into the PFC and hippocampus also increased ACh release in these brain regions. Treatment with parachlorophenylalanine and alpha-methyl-para-tyrosine, inhibitors of serotonin (5-HT) and dopamine (DA) synthesis, respectively, significantly attenuated the release of ACh stimulated by MDMA in the PFC, but not in the dorsal hippocampus.",
            "output": [
                "Does 3,4-Methylenedioxymethamphetamine enhance the release of acetylcholine in the prefrontal cortex and dorsal hippocampus of the rat?"
            ]
        },
        {
            "id": "task847-1d50d0527de243e6b6215ee6b8f9464a",
            "input": "emm types 12, 1, 28, 3, 4, 2 and 6 (in that order) are the types most commonly associated with uncomplicated group A streptococcal (GAS) pharyngitis in the United States, together accounting for approximately 78% of isolates.', 'To determine whether the distribution of common pharyngeal group A streptococcal GAS types differs at various ages throughout childhood.', 'We emm typed 3356 GAS isolates collected from the United States and Canada during 3 streptococcal seasons (2000-2003). Variations in prevalence by age for the 7 most prevalent emm types and the \"uncommon\" category (all types accounting for <5% of the total number of isolates) were analyzed and assessed for significance by chi2.', 'The proportion of uncommon isolates increased significantly with increasing age from 18% in group 1 to 37% in group 4 (P = 0.001). We found a significant decrease in the proportion of the common pharyngeal emm types, specifically emm 12 and emm 4 type isolates, with increasing age (P = 0.001 and P = 0.003, respectively); there was no significant decline in the prevalence of other common pharyngeal types (emm 1, 2, 3, 6 and 28) with increasing age.",
            "output": [
                "Does age influence the emm type distribution of pediatric group A streptococcal pharyngeal isolates?"
            ]
        },
        {
            "id": "task847-3fd63f13740c4e52821f57bfe796c5fc",
            "input": "Autosomal recessive juvenile parkinsonism (AR-JP) is caused by mutations in the parkin gene which encodes an E3 ubiquitin-protein ligase. Parkin is thought to be critical for protecting dopaminergic neurons from toxic insults by targeting misfolded or oxidatively damaged proteins for proteasomal degradation. Surprisingly, mice with targeted deletions of parkin do not recapitulate robust behavioral or pathological signs of parkinsonism. Since Parkin is thought to protect against neurotoxic insults, we hypothesized that the reason Parkin-deficient mice do not develop parkinsonism is because they are not exposed to appropriate environmental triggers. To test this possibility, we challenged Parkin-deficient mice with neurotoxic regimens of either methamphetamine (METH) or 6-hydroxydopamine (6-OHDA). Because Parkin function has been linked to many of the pathways involved in METH and 6-OHDA toxicity, we predicted that Parkin-deficient mice would be more sensitive to the neurotoxic effects of these agents.', 'We found no signs consistent with oxidative stress, ubiquitin dysfunction, or degeneration of striatal dopamine neuron terminals in aged Parkin-deficient mice. Moreover, results from behavioral, neurochemical, and immunoblot analyses indicate that Parkin-deficient mice are not more sensitive to dopaminergic neurotoxicity following treatment with METH or 6-OHDA.",
            "output": [
                "Are parkin-deficient mice more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity?"
            ]
        },
        {
            "id": "task847-e1323082d8c34659b13712cafc81e8ae",
            "input": "Close contacts of patients with leprosy have a higher risk of developing leprosy. Several risk factors have been identified, including genetic relationship and physical distance. Their independent contributions to the risk of developing leprosy, however, have never been sufficiently quantified.', 'Logistic-regression analysis was performed on intake data from a prospective cohort study of 1037 patients newly diagnosed as having leprosy and their 21,870 contacts.', 'Higher age showed an increased risk, with a bimodal distribution. Contacts of patients with paucibacillary (PB) leprosy with 2-5 lesions (PB2-5) and those with multibacillary (MB) leprosy had a higher risk than did contacts of patients with single-lesion PB leprosy. The core household group had a higher risk than other contacts living under the same roof and next-door neighbors, who again had a higher risk than neighbors of neighbors. A close genetic relationship indicated an increased risk when blood-related children, parents, and siblings were pooled together.",
            "output": [
                "Are physical distance , genetic relationship , age , and leprosy classification independent risk factors for leprosy in contacts of patients with leprosy?"
            ]
        },
        {
            "id": "task847-707e201967f84c358260afb61d9abd67",
            "input": "Autologous hematopoietic stem cell transplantation (auto-HSCT) patients experience long-term immunosuppression, which increases susceptibility to infection and relapse rates due to minimal residual disease (MRD). Sex steroid (SS) ablation is known to reverse age-related thymic atrophy and decline in B-cell production', 'This study used a congenic HSCT mouse model to analyze the effects of SS ablation (through surgical castration) on immune reconstitution and growth factor production following auto-HSCT. Bone marrow (BM) and thymic stromal cell (TSCs) populations were analyzed using RT-PCR and were tested for the production of growth factors previously implicated in immune reconstitution or age-relate immune degeneration', 'Castration increased bone marrow (BM), thymic, and splenic cellularity following auto-HSCT. HSC number and common lymphoid precursor (CLP) frequency and number were increased in castrated mice. B cell precursor numbers were also significantly increased in the BM of these mice. Triple negative, double positive and single positive thymocytes were increased following HSCT and castration, as were thymic dendritic cells and natural killer T (NKT) cells. This enhanced lymphoid reconstitution of the primary immune organs leads to a significant increase in splenic T and B cells 42 days after HSCT. The molecular mechanisms behind the enhanced reconstitution were also studied. TGF-beta1 was decreased in castrated mice compared to sham-castrated controls in TSCs and BM cells. TSC production of IL-6 was also decreased in castrated mice",
            "output": [
                "Does sex steroid ablation enhance lymphoid recovery following autologous hematopoietic stem cell transplantation?"
            ]
        },
        {
            "id": "task847-e719837d28fb406a80bfd73ac40e52c0",
            "input": "Azathioprine is an immunosuppressive and anti-inflammatory drug, and it has been shown to induce apoptosis in human T-lymphocytes. We investigated whether local treatment with azathioprine can inhibit neointimal hyperplasia in experimental vein grafts.', 'C57BL/6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a cuff technique. In the treatment group azathioprine was perivascularly applied. The control group did not receive local treatment. Vein grafts were harvested at 1 and 2 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL).', 'In grafted veins without treatment (controls), neointimal thickness was 10 microm (range, 6-29 microm), and 12 microm (range, 8-40 microm) at 1 and 2 weeks postoperatively, respectively. In azathioprine-treated grafts, the neointimal thickness was 2 microm (range, 1-5 microm) and 4 microm (range, 3-11 microm) at 1 and 2 weeks postoperatively, respectively. This reduction of neointimal thickness was significant at 1 week (P = .001) and 2 weeks (P = .016) postoperatively. Azathioprine-treated vein grafts showed an increased rate of apoptosis in the vascular wall as compared with controls (593 [range, 26-783] versus 45 [range, 0-106] apoptotic cells/mm(2) at 1 week, P = .063; and 656 [range, 327-1270] versus 19 [range, 0-79] apoptotic cells/mm(2) at 2 weeks, P = .016).",
            "output": [
                "Does perivascular treatment with azathioprine reduce neointimal hyperplasia in experimental vein grafts?"
            ]
        },
        {
            "id": "task847-e6459923db70451cab4f74daf73f7c1e",
            "input": "It has previously been shown that heparanase-1 (HPR1), an endoglycosidase, is up-regulated in pancreatic carcinoma. The purpose of this study was to test whether serum HPR1 levels in pancreatic carcinoma patients are elevated, and whether higher serum HPR1 levels are associated with a shortened survival.', 'Serum HPR1 levels in 40 healthy donors, 31 pancreatic carcinoma patients, and 11 patients treated with gemcitabine were measured by a novel enzyme-linked immunoadsorbent assay. HPR1 expression in tumors was analyzed by immunohistochemical staining. Patient overall survival time was determined according to the Kaplan-Meier method, and their difference was evaluated by the log-rank test. A P value<0.05 was considered statistically significant.', 'The mean serum HPR1 activity in pancreatic carcinoma patients was 439+/-14 units/mL, compared with 190+/-4 units/mL in the control serum samples from healthy donors. Serum HPR1 levels were significantly higher in patients with HPR1-positive tumors (660+/-62 units/mL) compared with those with HPR1-negative tumors (241+/-14 units/mL). The mean survival of 19 pancreatic carcinoma patients with serum HPR1 activity>300 units/mL was 7.9+/-0.2 months, whereas the mean survival of 12 patients with serum HPR1 activity<300 units/mL was 13.3+/-0.6 months. A Kaplan-Meier plot of the patient survival curve followed by log-rank test revealed that patients in the high serum HPR1 group had a significantly shorter survival compared with those in the low serum HPR1 group. Mean serum HPR1 activity decreased by 64% in 11 pancreatic carcinoma patients after 2 weeks of treatment with gemcitabine.",
            "output": [
                "Are elevated serum heparanase-1 levels in patients with pancreatic carcinoma associated with poor survival?"
            ]
        },
        {
            "id": "task847-fcdb4d447d9a4871b73d334fbd0cbcf3",
            "input": "We evaluated the impact of impermeable bed covers on asthma in asthmatics with clinically relevant house dust mite (HDM) sensitization.', 'The study included 32 HDM-sensitized asthmatics in whom HDM allergy was considered as a significant factor in their asthma. They were randomized into either an intervention group whose bedding was encased with impermeable covers, or a control group who received cotton covers. Before and 3 and 6 months after encasement, dust samples were collected from the bedding and assayed for Der p 1. Clinical outcomes included quality of life, lung function, bronchial reactivity to methacholine, symptoms, medications and peak flow rates.', 'Baseline Der p 1 levels in both the active and the placebo groups were comparable and high (19.2 vs 18.9 microg/g of dust). There was a significant reduction in Der p 1 levels in the active group after 6 months, but not in the placebo group (7.3 vs 21.9 microg/g of dust). Quality of life improved significantly in both the intervention and control groups, but there was no significant difference in the improvements between the groups. There was no significant change in lung function, symptoms, and requirements for medications.",
            "output": [
                "Does encasement of bedding improve asthma in atopic adult asthmatics?"
            ]
        },
        {
            "id": "task847-4fe98095163c41a4987b033561c679b6",
            "input": "Animal models suggest a genetic contribution to cerebral susceptibility to ischemia. Family history of stroke (FHxstroke) is a risk factor for ischemic stroke, but there is significant confounding by heritability of hypertension and other intermediate phenotypes, and it is uncertain whether genetic factors have a direct independent influence on cerebral susceptibility to ischemia in man.', 'We related detailed FHxstroke to baseline characteristics and subsequent risk of stroke in 2 population-based incidence studies and a consecutive hospital-referred series of patients with recent transient ischemic attack (TIA).', 'In none of the cohorts or the pooled data (757 patients; 5515 patient years follow-up; 200 ischemic strokes; 126 myocardial infarctions [MIs]) did FHxstroke predict ischemic stroke (odds ratio [OR], 0.87; 95% CI, 0.57 to 1.32). No associations were revealed by analyses stratified by age or hypertension in the proband, FHx(stroke) in parents versus siblings, number of affected relatives, or their age at stroke. FHxstroke was unrelated to presence of ischemic lesions on baseline computed tomography (OR, 0.96; 0.52 to 1.76) or risk of MI during follow-up. There was no bias attributable to any relationship between FHxstroke and risk factor control or medication.",
            "output": [
                "Does family history of stroke predict risk of stroke after transient ischemic attack?"
            ]
        },
        {
            "id": "task847-d5668baa16eb41048ceeb3afb9de36ce",
            "input": "Maternal serum concentrations of macrophage migration inhibitory factor (MIF) have recently been reported to be elevated in cases with preeclampsia. These findings may be important in increasing our understanding of the underlying events leading to the development of preeclampsia, as this cytokine is also expressed in the placenta, where it has been shown to possess immunemodulatory activities. For this reason we attempted to independently verify this report.', 'Plasma levels of MIF were assessed by ELISA in plasma samples collected from normal healthy male and female blood donors (n=20 per group), as well as healthy normal pregnant women in all three trimesters of pregnancy (n=60). In addition, MIF levels were examined from cases with mild and severe preeclampsia (n=20 per study cohort) and matched normotensive pregnancies (n=20).', 'MIF levels were found to be elevated in pregnancy (median=10.1 ng/ml) when compared to non-pregnant controls (median=1.7 ng/ml). A moderate, but not significant, elevation was found to occur from the first to the third trimester of pregnancy. No significant difference was found to occur between the two preeclampsia study groups when compared to the normotensive control group.",
            "output": [
                "Is macrophage migration inhibition factor elevated in pregnancy , but not to a greater extent in preeclampsia?"
            ]
        },
        {
            "id": "task847-0793e99bf21c40958900bd4cd035931a",
            "input": "Crohn's disease is associated with a host of factors potentially increasing the risk for osteoporosis and fractures. The aim of our study was to identify the most predictive factors for skeletal pathology in this patients.\", \"Using a cross-sectional study design, 146 randomly selected patients with Crohn's disease of variable disease activity who were given standard therapy to control disease activity, including glucocorticoids, and who attended the outpatient clinic of the Gastroenterology Unit on regular follow-up visits were studied. Bone mineral density (BMD) measurements and lateral X-rays of the spine were performed, and biochemical parameters of bone turnover, gonadal hormones and C-reactive protein (CRP) as markers of disease activity were measured in all patients.\", 'There were 61 men and 85 women, with a mean age of 43 years and mean disease duration of 20 years. The majority of patients (86%) had been treated with glucocorticoids at some stage during their illness at a median dose of 7.5 mg/day, 43% were currently using these agents and 66% had undergone an intestinal resection. Twenty-one percent of patients had below-normal 25-hydroxy vitamin D levels. Osteoporosis was documented in 26% of patients, predominantly at the femoral neck, but also at the lumbar spine or at both sites; osteopenia was documented in 45% of patients. Prevalence of vertebral and non-vertebral fractures was, respectively, 6% and 12%. Ileum resection was the most predictive factor for osteoporosis: RR 3.84 (CI 1.24-9.77, p=0.018), followed by age: RR 1.05 (CI 1.02-1.08, p<0.001) and current or past glucocorticoid use: RR 1.94 (CI 0.92-4.10, p=0.08).",
            "output": [
                "Is ileum resection the most predictive factor for osteoporosis in patients with Crohn 's disease?"
            ]
        },
        {
            "id": "task847-d157d68eb1ff4219b74abc794470a65c",
            "input": "Delirium has recently been shown as a predictor of death, increased cost, and longer duration of stay in ventilated patients. Sedative and analgesic medications relieve anxiety and pain but may contribute to patients' transitioning into delirium.\", 'In this cohort study, the authors designed a priori an investigation to determine whether sedative and analgesic medications independently increased the probability of daily transition to delirium. Markov regression modeling (adjusting for 11 covariates) was used in the evaluation of 198 mechanically ventilated patients to determine the probability of daily transition to delirium as a function of sedative and analgesic dose administration during the previous 24 h.', 'Lorazepam was an independent risk factor for daily transition to delirium (odds ratio, 1.2 [95% confidence interval, 1.1-1.4]; P = 0.003), whereas fentanyl, morphine, and propofol were associated with higher but not statistically significant odds ratios. Increasing age and Acute Physiology and Chronic Health Evaluation II scores were also independent predictors of transitioning to delirium (multivariable P values < 0.05).",
            "output": [
                "Is lorazepam an independent risk factor for transitioning to delirium in intensive care unit patients?"
            ]
        },
        {
            "id": "task847-9974bcc2b9cd457abc8b0572981b85e4",
            "input": "The E-cadherin (CDH1) gene has been implicated in prostate cancer (PCA) risk, however, the exact mechanism is unknown. Several polymorphisms, such as the C/A variant -160 base pairs from the transcription start site, in the CDH1 gene promoter region have been associated with cancer risk, mainly in European descent populations.', 'We screened the entire coding region and 3.0 kilobases of the CDH1 promoter for polymorphisms in 48 African Americans using dHPLC. Twenty-one (21) polymorphisms were observed. Four polymorphisms, including -160C/A, were genotyped in a genetic association study using incident PCA cases (N = 427) and unaffected controls (N = 337) of similar age from three different ethnic groups consisting of African Americans, Jamaicans, and European Americans.', 'We observed a significantly higher frequency of the -160A allele among European American PCA patients (27.5%) compared to the control group (19.7%) (P = 0.04). More importantly, among men of European ancestry under the age of 65 who possess the -160 A allele there was over three times increased risk for prostate cancer (P = 0.05). Also, the AACT haplotype bearing the -160A allele was significantly associated with PCA in European Americans (P = 0.04).",
            "output": [
                "Do e-cadherin polymorphisms and haplotypes influence risk for prostate cancer?"
            ]
        },
        {
            "id": "task847-e449e37f11cb4f8d8267d4e478c545b1",
            "input": "Overweight and obese individuals are more likely to be insulin resistant and at increased risk of adverse clinical outcomes. Questions remain as to whether waist circumference (WC) or body mass index (BMI) most effectively identifies insulin-resistant individuals.', 'This study quantified insulin-mediated glucose uptake (IMGU) in 330 apparently healthy volunteers and compared the relation between this value and measurements of WC and BMI.', 'IMGU was quantified via determination of the steady-state plasma glucose (SSPG) concentration during the insulin-suppression test. Differences in SSPG concentrations due to variations in WC within a given BMI category, as well as those due to differences in BMI within a given WC classification, were then compared.', 'BMI and WC correlated with each other (r = 0.78, P < 0.001) and equally with SSPG concentrations (r = 0.58 and 0.57, respectively; P < 0.001). When stratified by BMI, abdominally obese subjects within the overweight BMI category had higher SSPG concentrations than did those with a normal WC (P < 0.05). When classified by WC, subjects in the overweight BMI category had greater SSPG concentrations than did subjects in the normal BMI category within the normal WC category (P < 0.01), as did subjects in the obese BMI category in comparison with subjects in the overweight BMI category within the obese WC category (P < 0.01).",
            "output": [
                "Do body mass index and waist circumference both contribute to differences in insulin-mediated glucose disposal in nondiabetic adults?"
            ]
        },
        {
            "id": "task847-c7bcaa66f29f4a869fdb0459082ada65",
            "input": "The purpose of this study was to explore an applicable approach for prolonging the survival of heterogenetic skin grafts on burn wounds with CTLA4Ig.', 'An adenovirus vector named Ad-CTLA4Ig, which could express human CTLA4Ig fusion protein, was constructed. Infecting and replicating in 293 cells, more Ad-CTLA4Ig and recombinant human CTLA4Ig (rhCTLA4Ig) were prepared, respectively. In a rat flame thermal injury model, the effect of rhCTLA4Ig on survival time of human skin graft on the eschar-excised rat burn wound was observed. Meanwhile, the efficiency of Ad-CTLA4Ig infecting cultured skin fibroblasts, keratinocytes, and partial-thickness skin samples were checked by CTLA4Ig expression essay. Then, the Ad-CTLA4Ig was administered locally on the eschar-excised wound and dermis of the skin graft, and the survival time of the human skin graft on burn wound was measured. The influence of the systemic immune function by rhCTLA4Ig and Ad-CTLA4Ig were also determined.', 'The prepared rhCTLA4Ig from the supernatant of Ad-CTLA4Ig-infected 293 cells was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis sodium dodecyl sulfate poly-acrylamide gel electrophoresis and Western blot. It was found that CTLA4Ig could significantly prolong the xenogeneic skin graft survival in a dosage-dependent manner. Interestingly, the survival time was longer when CTLA4Ig was used 24 hours posttransplantation than that at hour 0. The expression of CTLA4Ig could be observed in the cultured skin fibroblasts, keratinocytes, and skin pieces soon after Ad-CTLA4Ig transfection, as demonstrated by either immunocellular chemistry or immunohistochemistry assay. When Ad-CTLA4Ig was locally administered during skin transplantation on burn wound, the survival time was increased from 7.9 days of control group to 21.6 days, whereas the systemic immune function was not affected.",
            "output": [
                "Do cTLA4Ig introduced by adenovirus vector locally to prolong the survival of xenogeneic skin grafts on rat burn wounds?"
            ]
        },
        {
            "id": "task847-1e4a0ff2b14f4ee4b913234a0c6acc13",
            "input": "beta-Catenin has been shown to play an important role in the formation of hair follicle-related tumors, including pilomatricomas. Several investigators have shown that beta-catenin gene mutation is observed in pilomatricomas. However, the relationship between the pattern of beta-catenin localization in the cell and beta-catenin gene mutation is still controversial.', 'This work was performed to determine the frequency of beta-catenin nuclear localization in pilomatricoma, the relationship between the pattern of beta-catenin localization and beta-catenin mutation, and the involvement of APC mutation.', 'Typical 32 pilomatricomas were examined for beta-catenin expression by immunostaining. Genomic DNA was extracted, amplified and sequenced from 23 pilomaticomas with nuclear beta-catenin staining and 4 pilomaticomas without nuclear beta-catenin staining. Mutations of beta-catenin gene were confirmed by subcloning assay and restriction endonuclease assay.', 'Using immunostaining, we found that 81% (26/32) of pilomatricomas displayed nuclear beta-catenin staining in basophilic cells. Sequence analysis revealed that 61% (14/23) contained mutations in exon 3 of beta-catenin. However, no mutations were detected in 4 pilomaticomas without beta-catenin nuclear staining. Detected mutations were adjacent to or abolished well-known regulatory phosphorylation sites of beta-catenin. APC gene mutations were not detected in 27 pilomatricomas with/without beta-catenin nuclear staining.",
            "output": [
                "Are beta-Catenin mutation and its nuclear localization confirmed to be frequent causes of Wnt signaling pathway activation in pilomatricomas?"
            ]
        },
        {
            "id": "task847-2c4685de9aad45e1a999c2bd222b390e",
            "input": "The high frequency of RhD (D) antigen among Taiwanese persons (99.67%) often imposes unnecessary risks of under-transfusion on D- patients awaiting D- blood. Also because of the rare occurrence of anti-D among Taiwanese persons, routine pretransfusion D typing has been discontinued in the Mackay Memorial Hospital since 1988. This report is the retrospective evaluation of the outcome of abolishing RhD typing for Taiwanese.', 'More than 10 years of alloantibody data at Mackay Memorial Hospital Blood Bank were reviewed. The cases with anti-D were further used to analyze the potency of D antigen and to observe whether there were differences in the incidence of anti-D before and after discontinuation of routine D typing among Taiwanese individuals.', 'The incidence of anti-D before and after discontinuation of routine pretransfusion D typing has remained unchanged. The immunogenicity of D and \"Mi(a)\" in Taiwanese persons is found to be similar. In terms of opportunity for immunization, however, the \"Mi(a)\" antigen (phenotype frequency 7.3% in Taiwanese persons) has become the most important blood group antigen in Taiwan.",
            "output": [
                "Does taiwan experience suggest that RhD typing for blood transfusion is unnecessary in southeast Asian populations?"
            ]
        },
        {
            "id": "task847-6211282616f2428bad2b6faa36a1ead7",
            "input": "Previously, we demonstrated that intranasal infection of BALB/c mice with respiratory syncytial virus (RSV) resulted in an early 40% reduction in alveolar fluid clearance (AFC), an effect mediated via P2Y purinergic receptors.', 'To confirm that RSV-induced inhibition of AFC is mediated by uridine triphosphate (UTP), and to demonstrate that inhibition of de novo pyrimidine synthesis with leflunomide prevents increased UTP release after RSV infection, and thereby also prevents inhibition of AFC by RSV.', 'BALB/c mice were infected intranasally with RSV strain A2. AFC was measured in anesthetized, ventilated mice by instillation of 5% bovine serum albumin into the dependent lung. Some mice were pretreated with leflunomide or 6-mercaptopurine.', 'RSV-mediated inhibition of AFC is associated temporally with a 20-nM increase in UTP and ATP content of bronchoalveolar lavage fluid, hypoxemia, and altered nasal potential difference. RSV-mediated nucleotide release, AFC inhibition, and physiologic sequelae thereof can be prevented by pretreatment of mice with the de novo pyrimidine synthesis inhibitor leflunomide, which is not toxic to the mice, and which does not affect RSV replication in the lungs. In contrast, pretreatment of mice with 6-mercaptopurine, an inhibitor of de novo purine synthesis, has no beneficial effect on AFC or other indicators of disease progression. Finally, RSV-mediated inhibition of AFC is prevented by volume-regulated anion channel inhibitors.",
            "output": [
                "Does leflunomide prevent alveolar fluid clearance inhibition by respiratory syncytial virus?"
            ]
        },
        {
            "id": "task847-13eaba0f9d564f639443d1d7a8559f53",
            "input": "Glucocorticoids (GCs) are highly effective in the treatment of asthma. However, some individuals have GC-insensitive asthma.', 'To evaluate the functional response to steroids of bronchoalveolar lavage (BAL) cells from sites of airway inflammation from patients with GC-insensitive versus GC-sensitive asthma. As well, to attempt to define the functional role of glucocorticoid receptor (GCR)beta (a splicing variant, and dominant negative inhibitor of, the classic GCRalpha) in controlling GCRalpha nuclear translocation and transactivation at a molecular level.', 'Fiberoptic bronchoscopy with collection of BAL fluid was performed on seven patients with GC-sensitive asthma and eight patients with GC-insensitive asthma. GCRalpha cellular shuttling in response to 10(-6) M dexamethasone treatment and GCRbeta expression were analyzed in BAL cells by immunofluorescence staining. The effects of overexpression and silencing of GCRbeta mRNA on GCRalpha function were assessed.', 'Significantly reduced nuclear translocation of GCRalpha in response to steroids was found in BAL cells from patients with GC-insensitive asthma. BAL macrophages from patients with GC-insensitive asthma had significantly increased levels of cytoplasmic and nuclear GCRbeta. It was demonstrated that GCRalpha nuclear translocation and its transactivation properties were proportionately reduced by level of viral transduction of the GCRbeta gene into the DO-11.10 cell line. RNA silencing of GCRbeta mRNA in human BAL macrophages from patients with GC-insensitive asthma resulted in enhanced dexamethasone-induced GCRalpha transactivation.",
            "output": [
                "Does increased glucocorticoid receptor beta alter steroid response in glucocorticoid-insensitive asthma?"
            ]
        },
        {
            "id": "task847-40815c9bbb864f1d9b013595d747f024",
            "input": "During allergic lung inflammation dendritic cells (DCs) direct the generation and function of effector T-helper type 2 cells. T-helper type 2 cells not only orchestrate the inflammatory processes in the tissue by inducing the accumulation and activation of proinflammatory cells but also induce IgE production by B cells. Thus, inhibitors of DC function should have therapeutic benefits in patients with allergies.', 'VAF347, a novel low molecular weight immunomodulator, is described and acts as an antiinflammatory compound by a dual mode of action.', 'VAF347 inhibited the function of human monocyte-derived DCs to induce T-cell proliferation and cytokine production. Mechanistically, this effect may be due to reduced expression of CD86, HLA-DR, and interleukin 6 by DCs. In addition, the compound inhibited IgE synthesis in an isotype-specific fashion by human B lymphocytes. In a mouse model of antigen-induced eosinophilic inflammation, VAF347 blocked lung eosinophilia, mucus hyperplasia, and serum IgE levels, representing the hallmarks of allergic lung inflammation. The biological effects in vivo are most likely mediated by the immunoregulatory role of VAF347 on DCs because allergic lung inflammation was also inhibited in B-cell-deficient mice.",
            "output": [
                "Does a novel low molecular weight inhibitor of dendritic cells and B cells block allergic inflammation?"
            ]
        },
        {
            "id": "task847-cd72523abe154eff9768fc0cf1bff95f",
            "input": "Human cases of hypersensitivity pneumonitis (HP) have been reported among machinists for over 10 yr. Although mycobacteria have been implicated as causal agents, this has not been established in experimental studies and the mechanisms remain unclear. Other constituents of in-use metalworking fluids (MWFs) may also contribute to the development of lung disease. We investigated the potential for Mycobacterium immunogenum (MI) in MWFs to induce HP.', 'Mice were exposed intranasally for 3 wk to MI (isolated from MWFs), Saccharopolyspora rectivirgula (positive control), saline, endotoxin, MWFs spiked with endotoxin and/or MI, used MWFs, and particulate-fortified used MWFs. Responses were assessed 96 h after the last exposure.', 'Mice exposed to MI in MWFs developed lung pathology consistent with HP along with significantly more monocytes and neutrophils in lung lavage, increased CD4+/CD8+ T-lymphocyte ratio, and marked pulmonary lymphocytosis on histologic examination when compared with saline-treated control mice. Mice with Grade 2 or higher pathology (0-4 point scale) exhibited significantly elevated macrophage inflammatory protein-1alpha and IL-10 and a trend toward higher RANTES 96 h after the final dose. Endotoxin coexposure augmented lung pathology.",
            "output": [
                "Does metalworking fluid with mycobacteria and endotoxin induce hypersensitivity pneumonitis in mice?"
            ]
        },
        {
            "id": "task847-07e761cb0d3a4eb1881871ca4f936558",
            "input": "Uncontrolled intra-abdominal bleeding is a common cause of death in trauma patients in the prehospital and perioperative settings. The detrimental effects of abdominal hypertension are well studied, but the potential therapeutic use of abdominal insufflation for hemostasis has not been fully explored. We measured the effect of abdominal insufflation on blood loss and physiologic outcomes in a swine model of blunt liver injury.', 'Twenty-one anticoagulated swine (32 +/- 3 kg) were anesthesized; laparotomy was performed to localize liver anatomy and to place loose tourniquettes isolating the porta hepatis and supra/infrahepatic vena cava. A captive bolt gun was used to create a grade V hepatic laceration, producing massive parenchymal injury as well as complex tears of the middle and right hepatic veins. Animals were randomized into either control (n = 10) or abdominal insufflation at 20 cm H(2)O pressure (n = 11) groups. Crystalloid was used to maintain a mean arterial pressure of 30 mm Hg. Arterial pressure and other physiologic variables were recorded for 20 minutes. Animals were then sacrificed and blood loss measured.', 'Blood loss was 69% lower in insufflated animals compared with controls (384 +/- 51 versus 1252 +/- 88 cc, p < 0.001). After 20 minutes, insufflated animals had significantly higher mean arterial blood pressure (32.2 +/- 4.2 versus 21.2 +/- 4.0 mm Hg) and lower total resuscitation volume (195 +/- 83 versus 1356 +/- 95 cc). Three pigs died in the control group (30%), whereas no insufflated animals died (p < 0.05).",
            "output": [
                "Does abdominal insufflation decrease blood loss and mortality after porcine liver injury?"
            ]
        },
        {
            "id": "task847-fe84ac87d821448fbd844e83c25b245c",
            "input": "The aim of this study was to compare the efficacy of surgery for spontaneous intracerebral hemorrhage with that of medical treatment, based on data from the Japan Stroke Registry Study.', 'From 1999 to 2001, 1010 patients with spontaneous intracerebral hemorrhage were registered in the Japan Standard Stroke Registry Study from 45 stroke center hospitals in Japan. The National Institutes of Health Stroke Scale (NIHSS), Japan Stroke Scale (JSS), and modified Rankin Scale scores were used to compare severity and improvement in patients given surgical and medical treatment.",
            "output": [
                "Does surgery for spontaneous intracerebral hemorrhage have greater remedial value than conservative therapy?"
            ]
        },
        {
            "id": "task847-27e4c6ce47654261a778e48d2e76fd3a",
            "input": "A previous study by the authors has shown that recombinant myocilin purified from a prokaryotic expression system increases outflow resistance in cultured human anterior segments. The present study was performed to determine whether full-length myocilin purified from a human trabecular meshwork cell expression system alters outflow resistance after infusion into human anterior segments.', \"A feline immunodeficiency virus vector encoding both full-length myocilin (amino acids 1-503 fused to C-terminal V5 and six-histidine epitopes) and puromycin resistance was used to transduce a transformed trabecular meshwork cell line (TM5). Stably expressing cells were selected with puromycin. Recombinant myocilin was purified from the media using nickel ion affinity chromatography. Control purifications were performed on media from parental TM5 cells. Anterior segments of human eyes were placed in organ culture and perfused with either Dulbecco's modified Eagle's medium (DMEM) or DMEM supplemented with 50% porcine aqueous humor. One eye received an anterior chamber exchange with recombinant myocilin (2 microg/mL), whereas the fellow eye received an equal volume of control. Immunohistochemistry was performed with anti-myocilin and anti-V5 antibodies. Native polyacrylamide gel electrophoresis was used to analyze myocilin complex formation in porcine aqueous humor.\", 'Recombinant myocilin in porcine aqueous humor increased outflow resistance in cultured human anterior segments (91% +/- 68% [mean +/- SD] versus 18% +/- 31% in fellow control eye; n = 9, P = 0.004). Maximum outflow resistance was obtained 5 to 17 hours after infusion and remained above baseline for >3 days. Recombinant myocilin also increased outflow resistance in eyes incubated in DMEM, but only if myocilin was preincubated with porcine aqueous humor (78% +/- 77% when preincubated in DMEM containing porcine aqueous humor versus 13% +/- 15% when preincubated with DMEM alone, n = 6, P = 0.03). Recombinant myocilin appears to form a complex in porcine aqueous humor with a heat-labile protein(s). Immunohistochemistry revealed the presence of myocilin in the juxtacanalicular region of the trabecular meshwork.",
            "output": [
                "Does perfusion of his-tagged eukaryotic myocilin increase outflow resistance in human anterior segments in the presence of aqueous humor?"
            ]
        },
        {
            "id": "task847-24da224b0fe54be1becfb4d97a02007a",
            "input": "To determine the role of factor V Leiden and prothrombin gene mutation in the pathogenesis of unexplained second and third trimester nonrecurrent fetal loss.', 'One hundred and fourteen women with unexplained nonrecurrent late fetal loss made up the study group, and 106 normal pregnant women with a history of delivery of at least one healthy fetus and no history of late fetal loss made up the control group. The study group was further divided into two subgroups: second (n = 36) and third (n = 78) trimester fetal loss. All women were tested for factor V Leiden and G20210A prothrombin gene mutations.', 'Twenty-one (18.4%) of the women in the study group and seven (6.6%) of the women in the control group were heterozygous carriers of factor V Leiden mutation (OR = 3.19). Eleven (9.6%) of the women in the study group and three (2.8%) of the women in the control group were heterozygous carriers of prothrombin gene mutation (OR = 3.66). In assessing with regard to trimesters, 18 (23%) factor V Leiden and 10 (12.8%) prothrombin gene mutations were present in the group of third trimester fetal loss (OR = 4.24 and OR = 5.04, respectively). Three (8.3%) factor V Leiden and one (2.7%) prothrombin gene mutation were detected in women with second trimester fetal loss (OR = 1.28 and OR = 0.40, respectively).",
            "output": [
                "Is third trimester nonrecurrent fetal loss associated with factor V Leiden and prothrombin gene mutations?"
            ]
        },
        {
            "id": "task847-f0c0fbc9c81d4ee582825b15f3452c57",
            "input": "A 34-year-old man presented with herpes simplex encephalitis (HSE), with magnetic resonance imaging (MRI) showing dense foci of restricted diffusion in the temporal lobe.', 'With treatment and clinical improvement, follow-up MRI done 8 days later showed complete resolution of the restricted diffusion abnormalities, whereas other MRI sequences suggested interval progression.",
            "output": [
                "Does magnetic resonance restricted diffusion resolution correlate with clinical improvement and response to treatment in herpes simplex encephalitis?"
            ]
        },
        {
            "id": "task847-fcea981afa8748208dbb677780c7af01",
            "input": "We describe the epidemiology of smoking behaviors in a national young adult sample and identify common and unique demographic, social, and psychological correlates of daily smoking and lifetime and current nicotine dependence by race/ethnicity.', 'Data are from the National Longitudinal Survey of Adolescent Health, wave III. Dependence was measured by the Revised Fagerstr\u00f6m Test for Nicotine Dependence. Logistic regressions were estimated.', 'Hispanic ethnicity, low education, parental and peer smoking, novelty seeking, early age of smoking onset, and pleasurable initial smoking experiences are significantly correlated with daily smoking and lifetime nicotine dependence. Depressive symptoms are uniquely associated with lifetime and current dependence. Few factors are highly associated with current dependence. Initial sensitivity to smoking has a significantly greater impact on daily smoking than on dependence. Correlates of smoking behaviors are mostly common across racial/ethnic groups, although parental and peer smoking are significant for Whites and Hispanics but not for African Americans.",
            "output": [
                "Does epidemiology and correlate of daily smoking and nicotine dependence among young adults in the United States?"
            ]
        },
        {
            "id": "task847-fe77f962f73344d1bebd84ace58dfc7b",
            "input": "The aim of this study was to evaluate the expression of vascular endothelial growth factor (VEGF) in response to retinoic acid (RA) in human retinal pigment epithelial cells.', 'Expression of VEGF in human ARPE-19 cells was determined by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). mRNA stability was assessed after the administration of actinomycin D. The induction of the VEGF gene by various RAs was also determined by semiquantitative RT-PCR.', 'All-trans retinoic acid (atRA) time-dependently increased VEGF mRNA levels. The effect of atRA was dose-dependent in a range between 10(-7) M and 10(-6) M. Treatment with actinomycin D revealed that atRA induces the VEGF gene at the transcriptional level. Of the various RAs tested, atRA was the most potent inducer of the VEGF gene.",
            "output": [
                "Does retinoic acid induce VEGF gene expression in human retinal pigment epithelial cells ( ARPE-19 )?"
            ]
        },
        {
            "id": "task847-e1638e8870454e00a7b967166cefebf8",
            "input": "To determine whether sympathetic nerves regulate expression of known angiogenic growth factors.', 'Surgical sympathectomy (SNX) was used to remove sympathetic innervation to the eye. Real-time PCR was used to measure steady state mRNA expression of VEGF, VEGFR-2, angiopoietin-1, and Tie2. Western blot analysis was performed to assess protein expression. Blood-retinal barrier (BRB) permeability surface area product (PS) was measured using enhanced MRI on a separate group of control and SNX rats.', 'mRNA of both VEGF and VEGFR-2 decreased significantly at 6 weeks after SNX. VEGF protein expression also decreased significantly. VEGFR-2 protein was unchanged. Both angiopoietin-1 and Tie2 mRNA expression increased significantly after SNX. Immunoblot analysis showed that angiopoietin-1 protein expression coincided with its mRNA expression. Tie2 protein expression was unaffected. Sympathetic denervation did not significantly increase BRB PS.",
            "output": [
                "Does superior cervical ganglionectomy induce changes in growth factor expression in the rat retina?"
            ]
        },
        {
            "id": "task847-264afd07bd76461aa95130ce1ec48982",
            "input": "To investigate the associations between C-reactive protein (CRP), homocysteine levels, use of hormone therapy (HT) and other factors.', \"A 12-year prospective study of 438 Australian-born women (Melbourne Women's Midlife Health Project), who at baseline were aged 45-55 years, had menstruated in the previous 3 months and were not taking HT. Fasting blood was collected in the 11th follow-up year for CRP, homocysteine, estradiol and follicle stimulating hormone (FSH) levels. Physical measurements and face-to-face interviews obtained information on health and lifestyle variables.\", 'A total of 258 women (mean age 60 years) participated in the 11th follow-up year. Multiple regression analysis found that CRP levels were positively associated with body mass index (p < 0.001), HT use (p < 0.01), and negatively associated with statin use (p < 0.005) and exercising (p < 0.05). In postmenopausal women currently not using HT (n = 173) and after adjusting for body mass index, exercise and smoking, CRP was negatively associated with FSH levels (beta = -0.32, p < 0.05). Homocysteine levels were positively associated with smoking (p < 0.001) and negatively associated with HT use (p < 0.05).",
            "output": [
                "Are serum C-reactive protein and plasma homocysteine levels associated with hormone therapy use and other factors : a population-based study of middle-aged Australian-born women?"
            ]
        },
        {
            "id": "task847-2827b3fe471c4d9b93de28842a9dcb81",
            "input": "Microalbuminuria and impaired endothelium-dependent vasodilation are both predictors for cardiac events in patients with type 2 diabetes. The aim of the study was to evaluate whether microalbuminuria correlated with coronary endothelium-dependent vasodilation.', 'We evaluated 84 patients (47 men, mean age 50.5 +/- 5.9 years) with type 2 diabetes for 9.4 +/- 3.4 years, without angiographic coronary stenosis and without major cardiovascular risk factors or other confounding factors, for endothelium investigation. Quantitative coronary angiography was used to assess coronary artery response to cold pressor testing, used to assess endothelium-dependent vasodilation, and to isosorbide dinitrate (endothelium-independent vasodilation).', 'Endothelium-dependent vasodilation differed in the patients with and without microalbuminuria (changes in coronary artery diameter during cold pressor testing: -15.0 +/- 1.9% vs. -10.2 +/- 1.3%, respectively, P < 0.05) and correlated with urinary albumin excretion rate (r = -0.39, P = 0.003), diastolic blood pressure (r = 0.29, P < 0.01), and left ventricular mass index (r = -0.24, P < 0.05). Independent predictors for endothelium-dependent vasodilation were urinary albumin excretion rate (beta -0.04 [95% CI -0.07 to -0.01], P < 0.005) and left ventricular mass index (-0.26 [-0.49 to -0.05], P < 0.05). Endothelium-independent vasodilation was similar in both groups.",
            "output": [
                "Is impaired coronary endothelium-dependent vasodilation associated with microalbuminuria in patients with type 2 diabetes and angiographically normal coronary arteries?"
            ]
        },
        {
            "id": "task847-652f5e9736cd4dcfb1e9b7d44d57e58f",
            "input": "We studied the association between polymorphisms in the UCP genes and diabetes complications in patients with type 1 diabetes.', 'We analyzed 227 patients with type 1 diabetes using PCR and subsequent cleavage by restriction endonucleases for the promoter variants A-3826G in the UCP1 gene, G-866A in the UCP2 gene, and C-55T in the UCP3 gene.', 'No effect of the A-3826G polymorphism in the UCP1 gene on diabetes complications was found. Patients who were heterozygous or homozygous for the G-866A polymorphism in the UCP2 gene or the C-55T polymorphism in the UCP3 gene had a significantly reduced prevalence of diabetic neuropathy (UCP2: odds ratio 0.44 [95% CI 0.24-0.79], P = 0.007; UCP3: 0.48 [0.25-0.92], P = 0.031), whereas there was no association with other diabetes complications. This effect was stronger when G-866A and C-55T occurred in a cosegregatory manner (UCP2 and UCP3: 0.28 [0.12-0.65], P = 0.002). Furthermore, a multiple logistic regression model showed an age- and diabetes duration-independent effect of the cosegregated polymorphisms on the prevalence of diabetic neuropathy (P = 0.013).",
            "output": [
                "Are functional polymorphisms of UCP2 and UCP3 associated with a reduced prevalence of diabetic neuropathy in patients with type 1 diabetes?"
            ]
        },
        {
            "id": "task847-ada73dd913bd4b7ca78ffcb1c4c1b80e",
            "input": "The objective of this study was to determine whether high levels of HDL cholesterol are associated with a lower prevalence of albuminuria', 'We analyzed the lipid profiles of patients with type 1 diabetes of > or = 20 years duration in 42 patients with albuminuria (28 microalbuminuria and 14 macroalbuminuria) and 65 patients without increased albumin excretion before any interventions with either statins or ACE inhibitors.', 'Several characteristics were similar in the two groups: sex, age, duration of diabetes, total cholesterol, LDL cholesterol, and triglycerides. By univariate analysis, significant differences (P < 0.01) were found in HDL cholesterol (albuminuria 1.42 mg/dl, no albuminuria 1.71 mg/dl, P < 0.01), HbA1c (A1C) (albuminuria 8.5%, no albuminuria 7.5%), and proportions with no, background, and proliferative retinopathy (albuminuria 2.4, 16.7, and 81%; no albuminuria 24.6, 52.3, and 23.1%, respectively). When adjusted for age and sex, a 0.26-mmol/l (10-mg/dl) increase in HDL cholesterol is associated with an odds ratio (OR) of 0.70 (95% CI 0.54-0.90) for having albuminuria. In a multivariate model that adjusted for age, sex, diabetes duration, and A1C, for every 0.54-mmol/l (21-mg/dl) increase in HDL cholesterol, patients are approximately half (OR 0.51 [95% CI 0.30-0.86]) as likely to have albuminuria, even after controlling for A1C.",
            "output": [
                "Are higher levels of HDL cholesterol associated with a decreased likelihood of albuminuria in patients with long-standing type 1 diabetes?"
            ]
        },
        {
            "id": "task847-a935b838677440f6a2c56e546f8a459e",
            "input": "To investigate the effects of quercetin, an herbal flavonoid, on LPS-induced delay in spontaneous apoptosis, adhesion molecules (CD62L, CD11b/CD18) expression of neutrophils, and superoxide (O(2)(-)) generation by LPS-primed fMLP-induced human neutrophils.', 'Neutrophils were incubated in the presence or absence of lipopolysaccharide (LPS) at a final concentration of 1 microg/ml for 24 hours. Some wells with neutrophils were pre-treated with quecetin at the final concentration ranging from 0-100 microM for 30 min and then 1 microg/ml LPS was added into the cultures for 24 hours. The apoptosis of neutrophils was evaluated by flowcytometry analysis of propidum iodide (PI)-staining of the nuclei and annexin V staining of phosphatidylserine (PS) in the cell membrane. Agarose gel electrophoresis of low molecular weight DNA was performed to analyze DNA fragmentation. The effects of quercetin on adhesion molecules were detected by using flowcytometry analysis. The generation of O(2) (-) by LPS-primed fMLP-induced neutrophils was determined by reduced cytochrome c assay.', 'LPS markedly inhibited the spontaneous apoptosis of neutrophils, but the inhibitory effect was abrogated after the pre-treatment of neutrophils with quercetin (approximately 40 microM) for 30 min. Quercetin (40 microM) also prevented LPS-induced down-regulation of CD62L expression, up-regulation of CD11b/CD18 expression, and O(2) (-) generation by fMLP-induced neutrophils.",
            "output": [
                "Does quercetin inhibit LPS-induced delay in spontaneous apoptosis and activation of neutrophils?"
            ]
        },
        {
            "id": "task847-f8e14045b70e462a8aeb046512aae706",
            "input": "Renal ultrasound is very important in the diagnosis of renal tumors.', 'From January 2000 to Jannuary 2005 we retrospectively examined the records of 116 patients, 37 women and 79 men (mean age 54 years, range 22-77), who underwent radical nephrectomy for kidney cancer in clinical stage CT1N0M0. 2.5 cm was the tumor dimension limit between the nephron sparing surgical technique and radical nephrectomy. We subdivided the sample into 2 groups, the first of 45 patients with tumor lesions smaller than 2.5 cm and the second with tumor lesions between 2.5 cm and 7 cm in diameter all patients underwent preoperative staging including ultrasound scan (ETG) and computer tomography scan (CT).', 'Ultrasound has showed 35% sensitivity and 49% specificity for lesions under 2.5 cm in diameter, and 65% sensitivity and 75% specificity and 80% specificity for lesions under 2.5 and 80% sensitivity and 95% specificity for lesions between 2.5 and 7 cm.",
            "output": [
                "Do detection rate of ultrasound vs CT scan in clinical staging accuracy of renal tumors pT1NxMx?"
            ]
        },
        {
            "id": "task847-53b5b0f862ff4bc8a45f3cf60a9ed2c1",
            "input": "To measure the serum highly sensitive C-reactive protein (hs-CRP) and adiponectin levels, assess insulin sensitivity index (SI) and acute insulin response (AIR) in normal control (NC) subjects, patients with impaired glucose tolerance (IGT) and newly diagnosed type 2 diabetes mellitus (DM), and further explore the possible correlation between hs-CRP and SI, AIR and adiponectin in IGT and newly diagnosed type 2 DM groups.', \"Age and sex matched 28 normal subjects, 31 patients with IGT, and 31 patients with newly diagnosed type 2 DM were included in the study. SI and AIR were assessed by the reduced sample number of Bergman's minimal model method with intravenous glucose tolerance test in subjects of each group.\", 'Compared with NC group, serum hs-CRP was significantly increased in IGT and type 2 DM groups (p < 0.001), although there was no significant difference between the latter groups. Hs-CRP was negatively correlated with high density lipoprotein cholesterol (HDL-C), SI and adiponectin levels (p < 0.05 to p < 0.001), and positively correlated with systolic blood pressure (SBP), fasting plasma glucose (FPG), BMI, waist-to-hip ratio (WHR), postprandial 2h plasma glucose (2hPG), fasting serum insulin (FINS) and postprandial serum insulin (PSI) in IGT and newly diagnosed type 2 DM groups (p < 0.05 to p < 0.001). In general multivariate regression, only adiponectin was the significantly independent determinant for serum hs-CRP (regression coefficient -1.380; 95% CI -2.062 to 0.698, p < 0.001); meanwhile, TG, SI, hs-CRP, FINS, 2hPG and WHR were significantly independent determinants for serum adiponectin concentration (p < 0.05 to p < 0.001).",
            "output": [
                "Are serum CRP levels equally elevated in newly diagnosed type 2 diabetes and impaired glucose tolerance and related to adiponectin levels and insulin sensitivity?"
            ]
        },
        {
            "id": "task847-75fb7aa6c5d84718bdcd9c5018f3aed0",
            "input": "We tested the hypothesis that oxytocin (OT) contracts blood vessels via vasopressin V1A (VP) receptors, and that this depends on pregnancy.', 'Concentration-contraction relationships (CCR) to OT and VP (10(-12)-10(-6) mol/L) were obtained in different blood vessels. CCR were obtained in uterine arteries (UA) from nonpregnant, mid-pregnant, and late pregnant rats (n = 6-10 per group) in the absence and presence of selective antagonists (10(-7) mol/L).', 'Sensitivity to OT, but not to VP, is attenuated in pregnant rat UA. Antagonists shifted CCR of OT and VP to the right, and, to a lesser extent, of the counterpart, in all UA. VP antagonist depresses oxytocin CCR much more than OT antagonist in pregnant rat UA.",
            "output": [
                "Does adaptation to pregnancy lead to attenuated rat uterine artery smooth muscle sensitivity to oxytocin?"
            ]
        },
        {
            "id": "task847-9839c2c1abc94c518c170cb0e76bdbb8",
            "input": "The previous study by the Polish Adult Leukemia Group has demonstrated that addition of cladribine to standard DNR+AraC induction potentiates the antileukemic activity. The goal of this study was to compare the efficacy of bone marrow or peripheral blood hematopoietic cell collection in patients who obtained remission after daunorubicine plus cytarabine induction with cladribine (DAC-7) or without addition of cladribine (DA-7) in preparation for autotransplantation.', 'Sixty-six patients aged 41 years (range, 17-58 years) were included in this study: 33 cases in the DAC-7 and 33 in the DA-7 arm. Hematopoietic cells were collected from the bone marrow (ABMT, n = 29) or from the peripheral blood (ABCT, n = 37) using cytopheresis after administration of AraC (2 x 2 g/m2) on days 1, 3, 5 and subsequent G-CSF (10 microg/kg) from day 7 as mobilization therapy.', 'The numbers of harvested CD34+ cells were similar in the DAC-7 and DA-7 pretreated patients both after harvesting from peripheral blood (2.55 x 10(6)/kg vs 2.5 x 10(6)/kg) and from bone marrow (1.62 x 10(6)/kg vs 1.55 x 10(6)/kg), respectively. The proportion of patients with sufficient material for autologous bone marrow transplantation was higher in the DAC-7 compared with the DA-7 arm. All patients engrafted; hematopoietic recovery was similar in both subgroups.",
            "output": [
                "Does addition of cladribine to induction/consolidation regimen impair peripheral blood stem cell mobilization and bone marrow harvest for autotransplantation in acute myeloid leukemia patients?"
            ]
        },
        {
            "id": "task847-525885a5e07a44078151f970694b9b18",
            "input": "To determine whether a paper-based antibiotic ordering system is an effective antibiotic stewardship measure.', 'An antibiotic order form (AOF) was introduced in July 2001 at a pediatric tertiary care hospital. Vancomycin courses prescribed before and after the AOF introduction were retrospectively reviewed based on Hospital Infection Control Practices Advisory Committee guidelines. The impact of the AOF on the appropriateness of vancomycin prescribing was evaluated in univariate and multivariable analyses that adjusted for other factors associated with appropriateness of vancomycin use. The density of vancomycin use after introduction of the AOF was also assessed.', 'Compliance with the AOF was poor (<50%) during the planned study period; therefore an additional 2 months of improved compliance (70-80%) were included. Rates of inappropriate vancomycin use increased during the study periods: 35% before AOF; 39% post-AOF; and 51% during the improved compliance period. On adjusted analysis, vancomycin utilization was significantly more inappropriate after introduction of the AOF. Vancomycin doses per 1000 patient days increased after introduction of the AOF.",
            "output": [
                "Does an antibiotic order form intervention improve or reduce vancomycin use?"
            ]
        },
        {
            "id": "task847-1367698670974da089646fa2d0d9db04",
            "input": "Thallium-201 (201Tl) myocardial perfusion imaging has been widely used for evaluation of myocardial ischemia/viability after myocardial infarction. The 3- to 4-h early redistribution imaging has underestimated a considerable part of viable myocardium, while the 24-h late redistribution imaging may enhance the detection of myocardial ischemia/viability, but remains controversial.', 'Thirty-eighty patients with myocardial infarction underwent the initial, 3-h, and 24-h redistribution imaging after intravenous injection of 148-185 MBq 201Tl. Image quality analysis was performed using a four-grade model: excellent, good, moderate, and poor. The initial and 3-h images, the initial and 24-h images, and the 3- and 24-h images were compared double-blinded.', 'The 3- and 24-h images showed no significant differences in image quality according to the four-grade model (P=.3580). Out of the 194 abnormal segments based on the initial imaging, 60 (31%) segments improved by at least one grade on the 3-h imaging, while 86 (44%) segments improved by at least one grade on the 24-h imaging. The 24-h late imaging detected more viable myocardium than the 3-h imaging did, with a significant difference (chi2=7.4235, P=.0064). There were 164 abnormal segments on the 3-h imaging, with an average 30% (48) segments improved by at least one grade on the 24-h imaging. There were 134 initial abnormal segments without any improvement on the 3-h imaging. Out of these segments, the 24-h late redistribution imaging detected additional redistribution in 30 segments, taking up 22%. The mean global score on the 3-h imaging significantly decreased compared to that on the initial imaging (t=5.71, P<.0001), and the mean global score on the 24-h imaging further decreased significantly compared to that on the 3-h imaging (t=6.28, P<.0001).",
            "output": [
                "Does twenty-four-hour thallium-201 late redistribution imaging enhance the detection of myocardial viability after myocardial infarction?"
            ]
        },
        {
            "id": "task847-2943c5d2ecb6441a9785b39ab6456a7b",
            "input": "This study was done to identify nurses' priorities for continued learning and to examine the priorities in relation to age, educational level, location in the organization, experience, position in the organization, and shift worked.\", \"A random sample of nurses at a Veterans Affairs Medical Center completed surveys consisting of 58 educational topics and demographic information. The results were analyzed using descriptive statistics, analysis of variance, and Tukey's HSD method to identify differences within the various subgroups of nurses.\", 'Of the 58 educational topics, 21 were determined to be high priority educational needs and were significantly correlated with one or more of the independent variables.",
            "output": [
                "Does continuing education need assessment of acute care and long-term-care nurses in a Veterans Affairs Medical Center?"
            ]
        },
        {
            "id": "task847-5216270d5b18436abe7cea7a9f1f4eb7",
            "input": "To determine the role of recipient lymphopenia state in the expansion and function of leukemia specific cytotoxic T lymphocytes (CTLs).', 'C57BL/6 mice were induced to lymphopenia with 6 Gy total body irradiation. Spleen T cells or leukemia specific T cells from EGFP+ transgenic C57BL/6-EGFP mice were adoptively transferred by intravenous injection. The mice were challenged subcutaneously with 1 x 10(6) FBL3 leukemic cells at day 2 after irradiation. The peripheral WBC count, percentage of EGFP+ cells, subsets of T cells and tumor sizes were monitored.', 'Both of the spleen T cell and leukemia specific CTL proliferated efficiently with the percentage of EGFP+ cells of 28. 81% and 42.24%, respectively, after infused into lymphopenic recipients. However, spleen T cells had no anti-leukemia effect regardless of its expansion. In contrast, leukemia specific CTLs showed a more rapid and extensive expansion under the condition of lymphopenia and a enhanced anti-leukemia immunity.",
            "output": [
                "Does [ Recipient lymphopenia state enhance the expansion and anti-leukemia effect of leukemia specific cytotoxic T lymphocytes ]?"
            ]
        },
        {
            "id": "task847-d1417a9d1523453ab5bd663032d4269b",
            "input": "To identify the gene responsible for autosomal dominant lamellar pulverulent cataract in a four-generation British family and characterise the functional and cellular consequences of the mutation.', 'Linkage analysis was used to identify the disease locus. The GJA8 gene was sequenced directly. Functional behaviour and cellular trafficking of connexins were examined by expression in Xenopus oocytes and HeLa cells.', 'A 262C>A transition that resulted in the replacement of proline by glutamine (P88Q) in the coding region of connexin50 (Cx50) was identified. hCx50P88Q did not induce intercellular conductance and significantly inhibited gap junctional activity of co-expressed wild type hCx50 RNA in paired Xenopus oocytes. In transfected cells, immunoreactive hCx50P88Q was confined to the cytoplasm but showed a temperature sensitive localisation at gap junctional plaques.",
            "output": [
                "Is a novel GJA8 mutation associated with autosomal dominant lamellar pulverulent cataract : further evidence for gap junction dysfunction in human cataract?"
            ]
        },
        {
            "id": "task847-af562aee52fe4e06b4c39bf94160537a",
            "input": "Endotoxin, when delivered shortly before or during mechanical ventilation, increases susceptibility to ventilation-associated lung injury. However, it is unclear whether increased susceptibility to ventilator-associated lung injury is still present after clinical recovery from a transient endotoxin challenge.', 'Anesthetized rats were submitted to a 4-h period of mechanical ventilation with low (8 ml/kg) or high (24, 27, or 30 ml/kg) tidal volumes (VTs) 24 h after transient illness had been provoked by a single nonlethal intravenous injection of Escherichia coli endotoxin. Control animals were injected with phosphate-buffered saline and underwent the same protocol.', 'At 24 h, endotoxin-treated nonventilated animals showed no symptoms of clinical illness, and oxygenation was comparable with that of controls, but lung neutrophil counts were increased. Compared with controls, mechanical ventilation with high VT induced a stronger pulmonary inflammatory response and more severe lung injury in endotoxin-treated animals, as indicated by impaired oxygenation, increased lung wet-to-dry weight ratio, and increased levels of protein, neutrophils, and cytokines in lung lavage fluid. In addition, the highest VT resulted in increased mortality in endotoxin-treated animals. Low VT after endotoxin treatment did not cause functional pulmonary impairment but induced an inflammatory response.",
            "output": [
                "Does increased susceptibility to ventilator-associated lung injury persist after clinical recovery from experimental endotoxemia?"
            ]
        },
        {
            "id": "task847-42400e0837ed4d1b95177decccfd1227",
            "input": "Although neuroendocrine (NE) cells in prostate cancer have been speculated to accelerate the growth and progression of surrounding cancer cells, the evidence is as yet inconclusive. We investigated the effect of an NE allograft (NE-10) and its cell line, NE-CS, which were established from the prostate of the LPB-Tag 12T-10 transgenic mouse, on human prostate cancer cell line LNCaP.', 'The proliferation and pulmonary metastasis of LNCaP xenografts in athymic mice with and without NE-10 allografts were evaluated. Boyden chamber assay and microarray analysis were performed to investigate changes in invasion/migration and mRNA of LNCaP cells under the influence of the NE cells, respectively.', 'NE-10 did not influence the proliferation of LNCaP. The pulmonary metastasis of LNCaP with NE-10 significantly increased compared to mice without it. The NE-CS cells accelerated the in vitro invasion/migration of adenocarcinoma cells. Increased expression of mRNA of gelsolin was observed in LNCaP cells incubated with the supernatant of NE-CS cells.",
            "output": [
                "Does murine androgen-independent neuroendocrine carcinoma promote metastasis of human prostate cancer cell line LNCaP?"
            ]
        },
        {
            "id": "task847-b308df54ab2548288be69f26d29324b4",
            "input": "The differential intestinal metabolism of the soy isoflavones is likely to influence the ability of soy to prevent prostate cancer. While daidzein, genistein, and equol have direct antiproliferative effects on prostatic epithelial cells in vitro, there are no such data for the isoflavone glycitein, or seven metabolites: O-desmethylangolensin (ODMA), 6-hydroxyODMA (6H-ODMA), dihydrodaidzein (DHD), cis-4-hydroxyequol (C4HE), 3'-hydroxydaidzein (3HD), 6-hydroxydaidzein (6HD), and 8-hydroxydaidzein (8HD). In the current study, the in vitro activities of these compounds were elucidated, and the active ranges of concentrations were compared to that found in Caucasian prostatic fluid (PF) and plasma samples.\", 'The effects of isoflavonoids on cell growth, cell cycle distribution, and apoptosis (active Caspase 3) were examined on benign prostatic epithelial cells (PrEC), and the prostate cancer cell line LNCaP.', 'PF concentrations of genistein, equol, and daidzein (but not ODMA or DHD) were often within the ranges that reduce PrEC growth in vitro. Profound differences in sensitivities were observed with LNCaP. The hydroxydaidzeins, C4HE, and 6H-ODMA had significant inhibitory effects at 10(-5)M on PrEC growth (but not LNCaP). Glycitein had significant effects on both. Reductions in cell growth were typically associated with both changes in cell cycle distribution and Caspase 3 activation. When five isoflavonoids were used in combination at concentrations present in PF samples, synergistic effects were observed.",
            "output": [
                "Are prostatic fluid concentrations of isoflavonoids in soy consumers sufficient to inhibit growth of benign and malignant prostatic epithelial cells in vitro?"
            ]
        },
        {
            "id": "task847-91085c01442d47e0b59c7c9ef6c0895b",
            "input": "Antimicrobial peptides are effector molecules of the innate immune response and contribute to host defense and inflammation. This study was designed to evaluate neovascularization in biopolymers after instillation with LL37 of angiogenesis in the dorsal skinfold chamber in mice.', \"The host defense peptide human cathelicicin LL37 was tested for in vitro antimicrobial activity in a bilayer radial diffusion assay. For in vivo testing, 4 different concentrations of LL37 or carrier control were instilled into a biopolymer, then inserted into the dorsal skinfold chamber in Balb/c mice. Standard microcirculatory parameters were assessed over 24 days' follow-up.\", 'LL37 showed broad-spectrum antimicrobial activity against gram-positive and -negative bacteria. The LL37 treatment of the biopolymer accelerated the onset of neovascularization by 6 days compared with the carrier control (P < 0.01).",
            "output": [
                "Does the human host defense peptide LL37/hCAP accelerate angiogenesis in PEGT/PBT biopolymers?"
            ]
        },
        {
            "id": "task847-caa9e1f8dca540888a3748219f14446d",
            "input": "The aim of this study was to determine the clinical significance and prognostic impact of extranodal metastasis (EM) in gastric carcinoma.', 'The study included 1023 patients who underwent gastrectomy with lymphadenectomy for primary gastric carcinoma between January 1993 and December 1996. EM was defined as the presence of tumour cells in extramural soft tissue that was discontinuous with either the primary lesion or locoregional lymph nodes.', \"EM was detected in 146 (14.3 per cent) of the 1023 patients and in 1060 (3.0 per cent) of the 35 811 nodules that were retrieved as 'lymph nodes' from adipose connective tissues. The incidence of EM was significantly higher in patients with tumours that were large (diameter 10 cm or more), infiltrative, deeply invading or undifferentiated and in those with lymph node, peritoneal or liver metastases, or lymphatic or vascular involvement. After curative operation overall survival was significantly worse for patients with EM than those without (P < 0.001). Multivariate analysis identified EM as an independent prognostic factor (hazard ratio 1.82 (95 per cent confidence interval 1.23 to 2.71); P = 0.003).",
            "output": [
                "Is extranodal metastasis an indicator of poor prognosis in patients with gastric carcinoma?"
            ]
        },
        {
            "id": "task847-f7c9c9c649ad4093aaa0cca7784b6d85",
            "input": "Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis.', 'We hypothesized that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT.', 'Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 mug Amb a 1) or placebo immunotherapy, then 12 weeks of omalizumab or placebo plus immunotherapy.', 'Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P = .044).",
            "output": [
                "Does omalizumab pretreatment decrease acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis?"
            ]
        },
        {
            "id": "task847-c10dafda6f844106b8c86efdcc5e8455",
            "input": "Eotaxin/CCL11 plays an important role in asthma. It acts through the chemokine receptor CCR3 expressed on hematopoietic and nonhematopoietic cells in the lung.', 'To determine whether eotaxin/CCL11 modulates lung and bronchial fibroblast properties and thereby might contribute to airway remodeling.', 'CCR3 expression was characterized on a lung fibroblast line (MRC-5; flow cytometry, fluorescent microscopy, RT-PCR, and Northern blotting), on primary bronchial fibroblasts (flow cytometry), and on fibroblasts in human lung tissue (confocal laser microscopy). The effects of eotaxin/CCL11 on lung fibroblast migration (Boyden chamber), proliferation (tritiated thymidine incorporation), alpha-smooth muscle actin expression (ELISA), 3-dimensional collagen gel contraction (floating gel), pro-alpha1(I) collagen mRNA (Northern blotting), total collagen synthesis (tritiated proline incorporation), matrix metalloproteinase activity (gelatin zymography), and TGF-beta(1) release (ELISA) were evaluated. The contribution of eotaxin/CCL11/CCR3 binding on lung fibroblasts was also investigated by neutralizing experiments.', 'CCR3 is constitutively expressed in cultured lung and primary bronchial fibroblasts and colocalizes with specific surface markers for human fibroblasts in lung tissue. Eotaxin/CCL11 selectively modulates fibroblast activities by increasing their proliferation, matrix metalloproteinase 2 activity, and collagen synthesis but not their differentiation into myofibroblasts, contractility in collagen gel, or TGF-beta(1) release. Eotaxin/CCL11 enhances migration of lung fibroblasts in response to nonspecific chemoattractants, and this effect is completely inhibited by anti-CCR3-neutralizing antibodies.",
            "output": [
                "Does the CC chemokine eotaxin/CCL11 have a selective profibrogenic effect on human lung fibroblasts?"
            ]
        },
        {
            "id": "task847-41e7978359934717af6beafb5eb67a35",
            "input": "Exposure to environmental tobacco smoke (ETS) has been shown to increase symptoms of allergic bronchial asthma, but direct effects on the expression of inflammatory markers have not been demonstrated thus far.', 'The aim of this study was to assess the correlation of ETS exposure with the expression of proinflammatory mediators in airway secretions, including IFN-gamma and IL-12, as well as IL-5 and IL-13, in allergic asthmatic schoolchildren and healthy control subjects.', 'By using the nasopharyngeal aspiration technique, airway secretions were collected from 24 atopic children with asthma (age, 6-16 years) and 26 healthy control subjects, and the concentration of cytokines was measured with immunoenzymatic methods.', 'IL-13 levels were highly increased in patients with asthma (P < .005), and parental tobacco smoke resulted in a significant increase in airway IL-13 secretion in these children compared with that seen in nonexposed children and healthy control subjects (median, 860 pg/mL vs 242 pg/mL and 125 pg/mL, respectively). Furthermore, a positive correlation between IL-13 levels and serum IgE concentrations (r(s) = 0.55) was found in children with allergic asthma.",
            "output": [
                "Is parental tobacco smoking associated with augmented IL-13 secretion in children with allergic asthma?"
            ]
        },
        {
            "id": "task847-6919569fd9be4084a470eb9de3ca33f4",
            "input": "To describe the range of sexual problems, as reported by men calling a help-line and to investigate factors associated with help seeking behaviour.', \"The study included all calls between 1999 and 2004. The information used for analysis comprised caller's demographic characteristics, the sexual problem reported, previous doctor contacts, coexisting physical and mental health problems.\", 'Erectile dysfunction (ED) and premature ejaculation (PE) were the most frequently reported problems (57 and 19.2% respectively). ED-reporting callers were older (OR 0.63 for the ages of 50-59 yrs), with co-morbidities (OR 1.75) and in stable relationship (OR 0.46), while PE-reporting callers were younger (OR 5.83 for the ages of 20-29 yrs), relatively healthy and more likely single (OR 2.62 and OR 2.92 respectively). Type and duration of sexual concern, age, coexisting health problems and marital status relate significantly (p<0.01) with willingness to seek medical help.",
            "output": [
                "Are erectile dysfunction and premature ejaculation the most frequently self-reported sexual concerns : profiles of 9,536 men calling a helpline?"
            ]
        },
        {
            "id": "task847-3078028384894f4fac0ef6c270024153",
            "input": "This study was designed to test whether early castration-induced short-term cellular changes in primary prostate tumours could predict clinical outcome in advanced disease.', 'Biopsies from 83 patients obtained before and within two weeks after surgical castration were investigated. Tumour epithelial cell apoptosis, proliferation, and prostate specific antigen (PSA) levels were quantified using immunohistochemistry, laser capture micro-dissection, and real time RT-PCR. Cellular effects were related to changes in serum PSA levels and clinical outcome.', 'Decreased proliferation and PSA mRNA levels, and increased apoptosis were observed in most tumours. These early cellular responses were not correlated to each other and did not predict serum PSA response or cancer-specific survival. A nadir PSA level below 1 ng/ml predicted a longer cancer-specific survival after castration therapy.",
            "output": [
                "Does the magnitude of early castration-induced primary tumour regression in prostate cancer predict clinical outcome?"
            ]
        },
        {
            "id": "task847-a92ce92e72214d4e9779b71c8d0538b4",
            "input": "There are limited and conflicting data available concerning the incidence of inadvertent splenectomy and its impact on the outcome in patients who have undergone oesophagectomy. The aim of this study is to identify the factors associated with a likelihood of inadvertent splenectomy and its influence on early and long-term outcome in patients having oesophagectomy for oesophageal carcinoma.', 'A consecutive series of 738 oesophagectomies performed between 1991 and 2004 was analysed. In our practice, the spleen was removed only if damaged intraoperatively. Routine chemo- and immunoprophylaxis would subsequently be used. Multivariate analysis with logistic and Cox models determined significant variables.', 'Of the 738 oesophagectomies, 48 (6.5%) had splenectomy. Neoadjuvant chemotherapy was administered to a minority of patients; none subsequently had splenectomy. There were significant differences between types of operation (Ivor-Lewis 18 (9.0%), left thoracolaparotomy 14 (9.9%) and left thoracophrenotomy 15 (3.9%), p=0.01). Splenectomy was more common with advanced N stage disease (OR=0.44 [0.20-0.95]; p=0.04). Splenectomy resulted in more blood transfusions (median, 2 units vs 0 units; p=0.03) more anastomotic leaks (7 [14.6%] vs 42 [6.1%]; p=0.02) but not an increase in pulmonary complications (p=0.64) or in-hospital mortality (1 [4.6%] vs 37 [5.4%]; p=0.30). Splenectomy did not significantly affect median survival (551 [332-770] days vs 627 [554-700] days; p=0.63).",
            "output": [
                "Does unplanned splenectomy during oesophagectomy affect survival?"
            ]
        },
        {
            "id": "task847-1fe65fd637b84de0a5a6405fd7e9a47d",
            "input": "To assess the incidence of retained products of conception (RPOC) in relation to transvaginal ultrasound performed after first-trimester uterine evacuation.', 'This was a prospective randomized study involving 809 women undergoing first-trimester uterine evacuation. The study group included 404 women in whom transvaginal sonography was performed at the end of the surgical procedure and the control group contained 405 women who did not undergo ultrasound examination. Initially, in the study group, recurettage was immediately performed if the endometrium appeared irregular but latterly only if endometrial thickness was > or = 8 mm. The patients were followed up by gynecological and ultrasound examinations 5-8 days following the surgical procedure.', 'The total complication rate was 4.3%. RPOC presented in three women in the study group (0.7%) and in 15 women in the control group (3.7%, P < 0.05). Vaginal bleeding requiring hospitalization occurred in two women in the study group (0.5%) vs. seven in the control group (1.7%, P = 0.2). Endometritis was diagnosed in one woman in the study group (0.2%) vs. six in the control group (1.5%) and uterine perforation occurred in one woman in the control group vs. none in the study group. There were no cases of RPOC in women who had an endometrial thickness of < 8 mm as demonstrated by ultrasound at the end of the surgical procedure.",
            "output": [
                "Does transvaginal ultrasound after first-trimester uterine evacuation reduce the incidence of retained products of conception?"
            ]
        },
        {
            "id": "task847-313f03db546c4b6f820a7ba52cfbd050",
            "input": "To determine whether repeat administration of an adenovector (Ad) into the eye results in efficient gene delivery and to test whether transgenes can be expressed from an adenovector expression system in the presence of preexisting, neutralizing anti-Ad antibodies.', 'To assess the efficiency of repeated gene delivery of an adenovector expression system, C57Bl/6 mice received one, two, or three injections (intravitreal [IVT] or periocular [PO]) of AdNull.11D (empty cassette) at 2-week intervals, followed by a single AdLuciferase (AdL.11D) IVT or PO injection. Mice were killed approximately 24 hours after AdL.11D injection and the eyes were enucleated and stored until assayed. Serum samples were also analyzed to determine whether repeated IVT or PO injections lead to induction of neutralizing antibodies directed against an adenovector delivery system. To determine whether preexisting neutralizing anti-Ad antibodies would block transgene expression, mice were preimmunized with one, two, or three intramuscular (IM) injection(s) of AdNull.11D (1 x 10(9) particle units [pu]). Fourteen days later, when systemic anti-Ad antibody titers were expected to exist, mice were given a single AdL.11D injection (IVT or PO) and killed, and the eyes and serum collected.', 'These studies show that multiple injections at 2-week intervals with adenovectors (IM, IVT, or PO) did not prevent transgene expression in the eye. Moreover, measurement of neutralizing anti-Ad antibody titers revealed that measurable anti-Ad antibody titers in mice did not ablate transgene expression.",
            "output": [
                "Does repeated administration of adenovector in the eye result in efficient gene delivery?"
            ]
        },
        {
            "id": "task847-f2e307b957e64fcca812cc986c5151ba",
            "input": "The purpose of this study was to determine the role of matrix metalloproteinases (MMP) in Pseudomonas aeruginosa keratitis.', 'Gene array and selective real-time PCR examined MMP expression in the cornea of susceptible (C57BL/6, B6) versus resistant (BALB/c) mice before and after infection; zymography tested enzyme activity for MMP-2 and -9. Clinical score, Langerhans cell (LC), and Neutrophil (PMN) quantitation were done in recombinant (r) MMP-9, antibody neutralized, and MMP-9(-/-) mice. The chemotactic potential of MMP-9 was tested in a Boyden chamber assay; light and transmission microscopy and immunostaining for collagen IV and MMP-9 were used to examine the effects and the source of MMP-9 after infection. ELISA was used to assess IL-1beta and MIP-2 levels.', 'Gene array (confirmed by PCR) revealed sixfold more MMP-9, and zymography showed greater enzyme activity in the infected cornea of B6 over BALB/c mice. rMMP-9 injection of BALB/c mice enhanced, whereas MMP-9 antibody neutralization in B6 mice and its absence in MMP-9(-/-) mice decreased corneal disease. MMP-9(-/-) and antibody neutralized mice had fewer LCs in cornea; rMMP-9-treated mice had more. A myeloperoxidase (MPO) assay showed a similar pattern for PMN. MMP-9 was not chemotactic for LC or PMN. The basement membrane was more intact in MMP-9(-/-) over wild-type infected mice and correlated with staining for collagen IV; PMN was a source of MMP-9. IL-1beta and MIP-2 were increased in rMMP-9 but decreased in MMP-9 antibody neutralized and MMP-9(-/-) over control groups.",
            "output": [
                "Does matrix metalloproteinase-9 amplify the immune response to Pseudomonas aeruginosa corneal infection?"
            ]
        },
        {
            "id": "task847-c7823da1f86c4517a983126233443bf0",
            "input": "To investigate whether leukocyte count, fibrinogen, von Willebrand factor (vWF) and plasminogen activator inhibitor-1 activity (PAI-1) are increased in subjects with the metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and the World Health Organisation (WHO).', 'Cross-sectional study.', 'A total of 520 overweight and obese subjects: 379 women and 141 men, visiting the weight management clinic of a University Hospital.', 'Waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting glucose were determined, and the presence or absence of the metabolic syndrome according to the NCEP-ATPIII criteria was assessed. In 349 subjects, data on the waist-to-hip ratio (WHR) and albumin excretion rate were available and the WHO criteria were applied. Insulin resistance was defined using the HOMA-IR index.', 'Subjects with the metabolic syndrome according to the NCEP-ATPIII criteria had significantly higher levels of leukocyte count (P < 0.001) and PAI-1 (P < 0.001), while no significant differences were found for fibrinogen or vWF (P > 0.05). Using the WHO criteria, similar results were found except for vWF, where higher levels were found in subjects with the metabolic syndrome. When subjects were classified according to the number of components of the metabolic syndrome, levels of leukocyte count, vWF and PAI-1 activity were significantly different (P < 0.05). In logistic regression analysis PAI-1, gender and leukocyte count were independent determinants of the metabolic syndrome (P < 0.001).",
            "output": [
                "Is among inflammation and coagulation markers , PAI-1 a true component of the metabolic syndrome?"
            ]
        },
        {
            "id": "task847-8b798a418916496dbebaa17bf6c48623",
            "input": "Neoadjuvant treatment is often given for locally advanced malignancies; however, clinical and experimental studies have shown that some chemotherapeutic agents impair wound healing. It has been reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) applied locally improves dermal wound healing. Thus, we investigated the effects of locally injected GM-CSF on abdominal wounds impaired by adriamycin, a widely used chemotherapeutic agent.', 'We divided 120 female Sprague-Dawley rats into five treatment groups of 24 rats. Group 1 received saline 8 mg/kg intravenously (i.v.) + laparotomy 14 days later (control); group 2 received 8 mg/kg i.v. adriamycin + laparotomy 14 days later; group 3 received adriamycin 8 mg/kg i.v. + laparotomy + local GM-CSF 50 microg 14 days later; group 4 received saline 8 mg/kg i.v. + laparotomy + local GM-CSF 50 microg 14 days later; and group 5 received adriamycin 8 mg/kg i.v. + laparotomy + systemic GM-CSF 50 microg 14 days later. Sutures were removed on postoperative day (POD) 7 in all five groups, and the abdominal bursting pressures were measured and recorded. Tissue samples were taken from the incision line for histopathological evaluation and hydroxyproline content measurement.', 'The bursting pressure was significantly lower in groups 2 and 5 than in groups 1, 3, and 4. The hydroxyproline content and histopathological findings supported this result.",
            "output": [
                "Does local granulocyte-macrophage colony-stimulating factor improve incisional wound healing in adriamycin-treated rats?"
            ]
        },
        {
            "id": "task847-5f40ec93a9ac49229d78f24c0f5c7c7c",
            "input": "The relationship between platelet activity and myocardial injury in patients with ST-segment elevated (ST-se) acute myocardial infarction (AMI) remains unclear. This study tested the hypothesis that platelet activity (expressed by CD62p) is enhanced and predictive of both the extent of myocardial damage and 30-day clinical outcome in patients with ST-se AMI undergoing primary coronary stenting.', 'Platelet CD62p expression prior to coronary angiographic was prospectively measured using flow cytometry in 45 consecutive patients with AMI undergoing primary coronary stenting. The CD62p expression was also evaluated in 20 healthy and 20 at-risk control subjects. The CD62p expression was significantly higher in AMI patients than in healthy and at-risk control subjects (all p values <0.0001). Patients with high CD62p expression (>or=8%) had significantly higher creatine kinase-MB (p<0.0001) levels, higher incidence of cardiogenic shock (p=0.009) upon presentation, significantly lower left ventricular ejection fraction (p=0.0003), and significantly higher incidence of 30-day composite major adverse clinical outcomes (MACO) (advanced congestive heart failure >or=class 3 or 30-day mortality) (p<0.0001) than those patients with low CD62p expression (<8%). Multiple stepwise logistic regression analysis demonstrated that only high CD62p expression (>or=8%) was an independent predictor of 30-day MACO (all p<0.0001).",
            "output": [
                "Is platelet activity a biomarker of cardiac necrosis and predictive of untoward clinical outcomes in patients with acute myocardial infarction undergoing primary coronary stenting?"
            ]
        },
        {
            "id": "task847-bc3e2a5554b7435994b415f107c08213",
            "input": "Pollination by insects that spend long periods visiting many flowers on a plant may impose a higher risk of facilitated self-pollination. Orchids and asclepiads are particularly at risk as their pollen is packaged as pollinia and so can be deposited on self-stigmas en masse. Many orchids and asclepiads have adaptations to limit self-deposition of pollinia, including gradual reconfiguration of pollinaria following removal. Here an unusual mechanism--anther cap retention--that appears to prevent self-pollination in the South African orchid Eulophia foliosa is examined.', 'Visits to inflorescences in the field were observed and pollinators collected. Visitation rates to transplanted inflorescences were compared between a site where putative pollinators were abundant and a site where they were rare. Anther cap retention times were determined for removed pollinaria and atmospheric vapour pressure deficit was recorded concurrently. Anther cap anatomy was examined using light microscopy.', 'Eulophia foliosa is pollinated almost exclusively by Cardiophorus obliquemaculatus (Elateridae) beetles, which remain on the deceptive inflorescences for on average 301 s (n = 18). The anther cap that covers the pollinarium is retained for an average of 512 s (n = 24) after pollinarium removal by beetles. In all populations measured, anther cap dimensions are greater than those of the stigmatic cavity, thus precluding the deposition of self-pollinia until after the anther cap has dropped. An anatomical investigation of this mechanism suggests that differential water loss from regions of the anther cap results in opening of the anther cap flaps. This is supported by observations that as atmospheric vapour pressure deficits increased, the duration of anther cap retention was reduced.",
            "output": [
                "Does anther cap retention prevent self-pollination by elaterid beetles in the South African orchid Eulophia foliosa?"
            ]
        },
        {
            "id": "task847-6029d6a9c1604859a434f1ad5cd1928a",
            "input": "The mechanisms through which transforming growth factor (TGF)-beta1 promotes intimal growth, and the pathways through which TGF-beta1 expression is regulated in the artery wall, are incompletely understood. We used a mouse model to investigate mechanisms of TGF-beta1-induced intimal growth.', 'Adenovirus-mediated overexpression of TGF-beta1 in uninjured carotid arteries of wild-type mice induced formation of a cellular and matrix-rich intima. Intimal growth appeared primarily due to cell migration and matrix accumulation, with only a negligible contribution from cell proliferation. Overexpression of TGF-beta1 also stimulated expression of plasminogen activator inhibitor type 1 (plasminogen activator inhibitor [PAI]-1) in the artery wall. To test the hypothesis that PAI-1 is a critical downstream mediator of TGF-beta1-induced intimal growth, we transduced carotid arteries of PAI-1-deficient (Serpine1(-/-)) mice with the TGF-beta1-expressing vector. Overexpression of TGF-beta1 in Serpine1(-/-) arteries did not increase intimal growth, matrix accumulation, cell migration, or proliferation. Moreover, TGF-beta1-transduced arteries of Serpine1(-/-) mice secreted 6- to 10-fold more TGF-beta1 than did arteries of wild-type mice that were infused with the same concentration of the TGF-beta1-expressing vector.",
            "output": [
                "Does transforming growth factor beta 1 induce neointima formation through plasminogen activator inhibitor-1-dependent pathways?"
            ]
        },
        {
            "id": "task847-7eb23e73d63b4c16b0e6afdc459eed60",
            "input": "Genomic islands are regions of bacterial genomes that have been acquired by horizontal transfer and often contain blocks of genes that function together for specific processes. Recently, it has become clear that the impact of genomic islands on the evolution of different bacterial species is significant and represents a major force in establishing bacterial genomic variation. However, the study of genomic island evolution has been mostly performed at the sequence level using computer software or hybridization analysis to compare different bacterial genomic sequences. We describe here a novel experimental approach to study the evolution of species-specific bacterial genomic islands that identifies island genes that have evolved in such a way that they are differentially-expressed depending on the bacterial host background into which they are transferred.', 'We demonstrate this approach by using a \"test\" genomic island that we have cloned from the Salmonella typhimurium genome (island 4305) and transferred to a range of Gram negative bacterial hosts of differing evolutionary relationships to S. typhimurium. Systematic analysis of the expression of the island genes in the different hosts compared to proper controls allowed identification of genes with genera-specific expression patterns. The data from the analysis can be arranged in a matrix to give an expression \"array\" of the island genes in the different bacterial backgrounds. A conserved 19-bp DNA site was found upstream of at least two of the differentially-expressed island genes. To our knowledge, this is the first systematic analysis of horizontally-transferred genomic island gene expression in a broad range of Gram negative hosts. We also present evidence in this study that the IS200 element found in island 4305 in S. typhimurium strain LT2 was inserted after the island had already been acquired by the S. typhimurium lineage and that this element is likely not involved in the integration or excision of island 4305.",
            "output": [
                "Does a new experimental approach for studying bacterial genomic island evolution identify island genes with bacterial host-specific expression patterns?"
            ]
        },
        {
            "id": "task847-917597cd653941b0900cd2123757be10",
            "input": "To determine the cellular mediators of antigen-induced arthritis (AIA) and the relative contribution of members of the interleukin-6 (IL-6) family and tumor necrosis factor (TNF) in AIA.', 'AIA was induced in mice deficient in T and B lymphocytes, IL-6 (IL-6(-/-)), TNF (TNF(-/-)), IL-11 receptor, and oncostatin M receptor, by immunization with methylated bovine serum albumin (mBSA) followed 7 days later by intraarticular injection of mBSA. Arthritis severity was assessed histologically, and T lymphocyte responses were assessed in vitro. Anti-TNF neutralizing antibody was administered to wild-type mice during AIA. Bone marrow osteoclasts were generated in vitro via culture with RANKL and macrophage colony-stimulating factor.', 'AIA was dependent on CD4+ T lymphocytes, but not CD8+ T lymphocytes or B cells. IL-6(-/-) mice had reduced AIA severity and fewer osteoclasts at sites of bone erosion. This protective effect was not seen with a deficiency of other IL-6 family members and was similar to that in TNF(-/-) mice or wild-type mice receiving TNF blockade treatment. IL-6(-/-) CD4+ T lymphocytes from draining lymph nodes had reduced antigen-induced proliferation and produced less IL-17 and less RANKL, relative to osteoprotegerin, than cells from wild-type mice. Bone marrow from IL-6(-/-) mice generated fewer osteoclasts in vitro than bone marrow from either wild-type or TNF(-/-) mice.",
            "output": [
                "Does interleukin-6 modulate production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis?"
            ]
        },
        {
            "id": "task847-52b9e0699ef846e58fcd1808cc87848f",
            "input": "To explore the effect of thymopentin (TP5) on the choice of ethanol and ameliorating withdrawal symptoms (anxiety) of ethanol in mice.', 'Mice were administered ethanol (v/v) in schedular fashion: 5% (1 week), 10% (1 week) and 15% (4 weeks), followed with the free choice between ethanol and water. Ethanol/(ethanol+water)x100% [E/(E+W)x100%] was measured as an index of ethanol selection. Light-dark box test and elevated plus maze test were chosen for the assessment of anxiety pre-drug and post-drug. After TP5 [0.2 mg/(kgxd), 0.4 mg/(kgxd)], i.p. or saline (vehicle control), i.p. for 14 days, the procedure was repeated.', '(1) E/(E+W)x100%: the post-drug values of TP5 (0.2 mg/kg, 0.4 mg/kg) were lower significantly than the pre-drug values. (2) Light-dark box test: the post-drug values of number of entries and time spent in the light chamber of TP5 (0.2 mg/kg, 0.4 mg/kg) were more than the pre-drug values themselves and the post-drug value of saline. (3) Elevated plus maze test: the post-drug values of time spent on open arms of TP5 (0.2 mg/kg, 0.4 mg/kg) were more than the pre-drug values themselves and the post-drug value of saline\u00ecand the post-drug values of time spent on close arms of TP5 were less than the pre-drug values.",
            "output": [
                "Are [ Withdrawal symptoms of ethanol ameliorated by thymopentin in mice ]?"
            ]
        },
        {
            "id": "task847-aaf2e8c8b4cd4cee930952300bc76f98",
            "input": "Gestational diabetes mellitus (GDM), defined by two abnormal glucose values on a 3-h oral glucose tolerance test (OGTT), is associated with insulin resistance and a low serum concentration of adiponectin. The metabolic implications of impaired glucose tolerance (IGT) of pregnancy (i.e., a single abnormal value on an OGTT), however, are not well established. We sought to evaluate the metabolic phenotype of pregnant women with IGT in relation to the timing of their isolated hyperglycemia.', 'A cross-sectional study was performed in pregnant women undergoing a 3-h, 100-g OGTT. The OGTT stratified participants into four groups: 1) GDM (n = 48), 2) 1-h IGT (single elevated value at 1 h) (n = 15), 3) 2-h/3-h IGT (single elevated value at either 2 or 3 h) (n = 23), and 4) normal glucose tolerance (NGT) (n = 93). Insulin sensitivity was measured by the validated insulin sensitivity index (IS(OGTT)) of Matsuda and DeFronzo.', 'Measures of severity of glycemia (fasting glucose, area under the glucose curve from the OGTT, and glucose challenge test result) were highest in the GDM group, followed by the 1-h IGT, 2-h/3-h IGT, and NGT groups, respectively (each trend P < 0.0001). Consistent with this finding, IS(OGTT) was highest in the NGT group (5.1), followed by the 2-h/3-h IGT (4.6), 1-h IGT (3.8), and GDM (3.2) groups (trend P < 0.0001). Furthermore, on multiple linear regression analysis of IS(OGTT), both GDM and 1-h IGT were independently associated with reduced insulin sensitivity (whereas 2-h/3-h IGT was not). Mean adjusted adiponectin was highest in the NGT group (15.7 microg/ml), followed by the 2-h/3-h IGT (15.6 microg/ml), 1-h IGT (13.7 microg/ml), and GDM (12.0 microg/ml) groups (trend P = 0.0024).",
            "output": [
                "Is impaired glucose tolerance of pregnancy a heterogeneous metabolic disorder as defined by the glycemic response to the oral glucose tolerance test?"
            ]
        },
        {
            "id": "task847-38464d177bb845a69d8f0542928fbc1d",
            "input": "Determine whether antioxidant supplements alter the plasma glutathione and/or cysteine redox potential in age-related macular degeneration (AMD) patients.', 'This was an ancillary study to the Age-Related Eye Disease Study (AREDS), where subset of AREDS subjects at two sites were studied at two time points, an average of 1.7 and 6.7 years after enrollment.', 'Plasma glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), and cystine (CySS) were measured by high-performance liquid chromatography, and redox potentials of GSH/GSSG (E(h) GSH) and Cys/CySS (E(h) Cys) were calculated. The means of the metabolites and redox potentials were compared by repeated-measures analysis of variance for subjects receiving antioxidants and those not receiving antioxidants.', 'At the first blood draw, the means for the antioxidant group (n = 153) and no antioxidant group (n = 159) were not significantly different for any of the metabolites or redox potentials. At the second draw, the GSH parameters were not significantly different between the antioxidant (n = 37) and no antioxidant (n = 45) groups; however, mean Cys was significantly higher in the antioxidant group (9.5 vs 7.2 micromol/l, P = .008). Also, mean E(h) Cys was significantly more reduced in the antioxidant group (-74 vs -67.3 mV, P = .03).",
            "output": [
                "Do antioxidant supplements prevent oxidation of cysteine/cystine redox in patients with age-related macular degeneration?"
            ]
        },
        {
            "id": "task847-ffb4d9c0bd3b437f97458d6e0153d333",
            "input": "To explore the prevalence of work disability (WD) and to identify bio-psychological factors that predicts future WD in rheumatoid arthritis (RA) over a 7-year period.', 'Patients were selected from the Oslo RA register. The prevalence of WD was studied cross-sectionally among respondents <67 years (n = 526) in a postal survey. Mean age (SD) was 51.1 (11.9) years, mean disease duration 11.3 (9.4) years, and 49% of patients were RF-positive. The patients studied for predictive factors for WD were respondents in postal surveys both at baseline and at the 7-year follow-up, in work at baseline and still in working age (<67 years) at follow-up (n = 159). Mean age at baseline (SD) was 44.5 (9.7) years, mean disease duration 8.4 (6.6) years, mean years of formal education 12.7 (3.1) years, 48% were RF-positive. Assessments included socio-demographic variables and health status measures (MHAQ, AIMS2, SF-36, fatigue and pain on VAS 0-100 mm, self efficacy, and RAI as a measure for helplessness).', 'Among the 526 respondents at baseline <67 years, the prevalence of WD was 40%. A high level of education was a predictor of reduced risk of work disability [odds ratio (OR) = 0.4, 95% confidence interval (CI) 0.1; 0.9], while female gender (OR 3.0, 95% CI 1.1; 8.0), physical disability (MHAQ-score) (OR = 3.9, 95% CI 1.2; 12.5) and helplessness over median RAI-score (OR = 3.0, 95% CI 1.4; 6.7) were independent predictors of increased risk for new work disability over 7 years.",
            "output": [
                "Is work disability in rheumatoid arthritis predicted by physical and psychological health status : a 7-year study from the Oslo RA register?"
            ]
        },
        {
            "id": "task847-36ef22e1ba14405d8867596379cd6859",
            "input": "The aim of the present study is to examine the effects of N-acetylcysteine (NAC), a thiol-containing anti-oxidant, on renal function and morphology, and biomarkers of oxidative stress, in rats subjected to renal ischaemia-reperfusion (IR).', 'Sprague-Dawley rats underwent unilateral nephrectomy and either contralateral renal IR (40 min of renal arterial clamping), or sham manipulation. Treatment groups were: (1) IR-Saline, (2) IR-NAC, (3) Sham-Saline and (4) Sham-NAC. The N-acetylcysteine was administered in a dose of 200 mg/kg intraperitoneally at 24, 12 and 2 h before, and 24, 48 and 72 h after, renal IR. Plasma creatinine was measured on days 1, 3 and 7 after IR, and kidney histology was assessed on day 7. In separate groups of animals we measured renal levels of the anti-oxidant glutathione, markers of systemic oxidative stress (plasma ascorbyl radical, urinary 8-iso-prostaglandin F2alpha), and glomerular filtration rate (GFR) by 51Cr-EDTA clearance, on day 1 after renal IR.', 'Treatment with NAC ameliorated the decline in GFR and reduced hyperkalaemia on day 1 (P<0.05), lowered plasma creatinine levels on days 1 and 3 (P<0.05), and decreased renal interstitial inflammation on day 7 (P<0.05), after renal IR. Kidney glutathione levels decreased significantly in group IR-Saline in response to IR (P<0.05), but were completely repleted in group IR-NAC. Groups with renal IR injury and acute renal failure showed increased plasma ascorbyl radical levels, and elevated urinary 8-iso-prostaglandin F2alpha excretion, compared with sham (P<0.05). N-acetylcysteine treatment reduced plasma ascorbyl concentrations 24 h after renal IR (P<0.05), but had no effect on the rate of urinary 8-iso-prostaglandin F2alpha excretion.",
            "output": [
                "Does n-acetylcysteine attenuate kidney injury in rats subjected to renal ischaemia-reperfusion?"
            ]
        },
        {
            "id": "task847-9e0a660834f14e0293a7a417e964eb6d",
            "input": "Laparoscopic splenectomy has been increasingly used in patients with idiopathic thrombocytopenic purpura. Because it is associated with minimal abdominal trauma, platelet consumption could be reduced with the laparoscopic approach. The aim of this study was to analyze intraoperative bleeding and the need for apheresis platelets, comparing laparoscopic with open splenectomy.', 'Records of 40 patients who underwent splenectomy (20 through laparoscopy and 20 through open surgery) for idiopathic thrombocytopenic purpura were retrospectively reviewed. Intraoperative bleeding and need of perioperative apheresis platelets were evaluated in both groups. Statistical evaluation was conducted using the Mann-Whitney rank test, and differences were considered significant at P<0.01.', 'The mean amount of intraoperative bleeding was less in the laparoscopic group (P<0.01). Apheresis platelets were necessary in all patients in the open group (2 units transfused in 55% and 1 unit in 45% of cases) and only in 30% of cases in the laparoscopic group (1 unit transfused in each case).",
            "output": [
                "Does laparoscopic splenectomy reduce the need for platelet transfusion in patients with idiopathic thrombocytopenic purpura?"
            ]
        },
        {
            "id": "task847-5ac9517949494f5cb7d0006dbdc6f4bf",
            "input": "Noninvasive pacemaker stress echocardiography is a newly introduced method for the diagnosis of coronary artery disease in patients with a permanent pacemaker. The prognostic value of pacemaker stress echocardiography has not been studied.', 'We studied 136 patients (mean age 64+/-12 years) with a permanent pacemaker who underwent pacemaker stress echocardiography for evaluation of coronary artery disease. All patients underwent pacemaker stress echocardiography by external programming (pacing heart rate up to ischemia or target heart rate).', 'Thirty-one patients (23%) had normal study results. Ischemia was detected in 75 patients (55%). During a mean follow-up of 3.5+/-2.4 years, 35 deaths (26%) (20 the result of cardiac causes) and 2 nonfatal myocardial infarctions (1%) occurred. The annual cardiac death rate was 1.3% in patients without ischemia and 4.6% in patients with ischemia (P=.01). The annual all-cause mortality rate was 3.1% in patients without ischemia and 7% in patients with ischemia (P=.004). The presence of ischemia during pacemaker stress echocardiography was the strongest independent predictor of cardiac death (hazard ratio 4.1, confidence interval 1.2-14.5) and all-cause mortality (hazard ratio 2.7, confidence interval 1.2-6.0) in a multivariable model.",
            "output": [
                "Does pacemaker stress echocardiography predict cardiac events in patients with permanent pacemaker?"
            ]
        },
        {
            "id": "task847-df59827545594b88a92dfeb14d69ae8c",
            "input": "Airway remodeling in asthma is the result of increased expression of connective tissue proteins, airway smooth muscle cell (ASMC) hyperplasia and hypertrophy. TGF-beta1 has been found to increase ASMC proliferation. The activation of mitogen-activated protein kinases (MAPKs), p38, ERK, and JNK, is critical to the signal transduction associated with cell proliferation. In the present study, we determined the role of phosphorylated MAPKs in TGF-beta1 induced ASMC proliferation.', 'Confluent and growth-arrested bovine ASMCs were treated with TGF-beta1. Proliferation was measured by [3H]-thymidine incorporation and cell counting. Expressions of phosphorylated p38, ERK1/2, and JNK were determined by Western analysis.', 'In a concentration-dependent manner, TGF-beta1 increased [3H]-thymidine incorporation and cell number of ASMCs. TGF-beta1 also enhanced serum-induced ASMC proliferation. Although ASMCs cultured with TGF-beta1 had a significant increase in phosphorylated p38, ERK1/2, and JNK, the maximal phosphorylation of each MAPK had a varied onset after incubation with TGF-beta1. TGF-beta1 induced DNA synthesis was inhibited by SB 203580 or PD 98059, selective inhibitors of p38 and MAP kinase kinase (MEK), respectively. Antibodies against EGF, FGF-2, IGF-I, and PDGF did not inhibit the TGF-beta1 induced DNA synthesis.",
            "output": [
                "Does tGF-beta1 increase proliferation of airway smooth muscle cells by phosphorylation of map kinases?"
            ]
        },
        {
            "id": "task847-5f1cc66eebe44fce8b38f77d00fd9055",
            "input": "Chronic atrial fibrillation (AF) is characterized by a remodeling process which involves the development of fibrosis. Since angiotensin II has been suspected to be involved in this process, the aim of our study was to investigate a possible influence of an ACE-I therapy in patients with chronic AF regarding the occurrence of left atrial structural remodeling.', 'Atrial tissue samples were obtained from patients with lone chronic AF or sinus rhythm (SR). Collagen I, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) protein expression were measured by quantitative Western Blotting techniques and calculated as mean +/- SEM. Histological tissue samples were used for calculating microvessel density (microvessel/mm(2) +/- SEM).', 'In AF, the collagen amount was higher (1.78 +/- 0.21; p = 0.01) vs. SR (0.37 +/- 0.07) accompanied by declining microcapillary density (AF: 145 +/- 13 vs. SR: 202 +/- 9; p = 0.01). Additionally, a negative correlation (p = 0.01) between collagen content and microcapillary density was observed. To investigate the influence of an ACE-I therapy on this remodeling process, patient groups were divided into AF and SR both with or without ACE-I. Interestingly, there was a significantly lower expression of collagen I in AF with ACE-I (1.04 +/- 0.26) vs. AF without ACE-I treatment (2.07 +/- 0.24, p = 0.02). The microcapillaries were not diminished in AF with ACE-I (180 +/- 15) vs. SR with ACE-I (196 +/- 9), but there was a significant rarification in AF without ACE-I (123 +/- 18; p = 0.03). The expression of VEGF and bFGF did not reveal any significant differences.",
            "output": [
                "Does aCE-inhibitor treatment attenuate atrial structural remodeling in patients with lone chronic atrial fibrillation?"
            ]
        },
        {
            "id": "task847-36fbb845b76642fd9c2df1bccf0e7c8b",
            "input": "To characterize the functional consequences of disease-associated mutations in the CNGB3 (B3) subunit of human cone photoreceptor cyclic nucleotide-gated channels in order to gain insight into disease mechanisms.', 'Three separate disease-associated mutations were generated in CNGB3: F525N, R403Q, and T383fsX. These mutant subunits were then heterologously expressed in Xenopus oocytes in combination with wild type CNGA3 (A3) subunits, and characterized by patch-clamp recording in the inside-out configuration.', 'Co-expression of A3 and B3F525N, A3 and B3R403Q, or A3 and B3R403Q and B3T383fsX subunits resulted in channels that exhibited an increase in ligand sensitivity without a reduction in current density compared to wild-type heteromeric channels. Each simulated disease state produced channels that exhibited greater sensitivity to block by L-cis-diltiazem than homomeric CNGA3 channels, confirming that the mutant CNGB3 subunits were competent to form functional heteromeric channels. Each combination of subunits displayed an increase in apparent affinity for cGMP relative to wild-type heteromeric channels. However, F525N enhanced cGMP apparent affinity to a significantly greater extent than the other two modeled disease states.",
            "output": [
                "Do disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels?"
            ]
        },
        {
            "id": "task847-70187aae7cb84f069a1ee37a51631c56",
            "input": "Oxidants are believed to play a major role in the development of emphysema.', 'This study aimed to determine if the expression of human copper-zinc superoxide dismutase (CuZnSOD) within the lungs of mice protects against the development of emphysema.', 'Transgenic CuZnSOD and littermate mice were exposed to cigarette smoke (6 h/d, 5 d/wk, for 1 yr) and compared with nonexposed mice. A second group was treated with intratracheal elastase to induce emphysema.', 'Lung inflammation was measured by cell counts and myeloperoxidase levels. Oxidative damage was assessed by immunofluorescence for 3-nitrotyrosine and 8-hydroxydeoxyguanosine and lipid peroxidation levels. The development of emphysema was determined by measuring the mean linear intercept (Lm).', 'Smoke exposure caused a fourfold increase in neutrophilic inflammation and doubled lung myeloperoxidase activity. This inflammatory response did not occur in the smoke-exposed CuZnSOD mice. Similarly, CuZnSOD expression prevented the 58% increase in lung lipid peroxidation products that occurred after smoke exposure. Most important, CuZnSOD prevented the onset of emphysema in both the smoke-induced model (Lm, 68 exposed control vs. 58 exposed transgenic; p < 0.04) and elastase-generated model (Lm, 80 exposed control vs. 63 exposed transgenic; p < 0.03). These results demonstrate for the first time that antioxidants can prevent smoke-induced inflammation and can counteract the proteolytic cascade that leads to emphysema formation in two separate animal models of the disease.",
            "output": [
                "Does superoxide dismutase expression attenuate cigarette smoke- or elastase-generated emphysema in mice?"
            ]
        },
        {
            "id": "task847-21f255360e3e483c9b70c37e37197b09",
            "input": "To examine the effects of intracoronary PhotoPoint photodynamic therapy (PDT) with a new photosensitiser, MV0611, in the overstretch balloon and stent porcine models of restenosis.', '28 pigs were injected with 3 mg/kg of MV0611 systemically 4 h before the procedure. Animals were divided into either the balloon overstretch injury (BI) group (n = 19) or the stented group (n = 9). After BI, a centred delivery catheter was positioned in the artery to cover the injured area, and light (532 nm, 125 J/cm(2)) was applied to activate the drug (n = 10). Control arteries (n = 9) were not activated by light. In the stented group, the drug was light activated before stent deployment. Serial sections of vessels were processed 14 days after treatment in the BI group and 30 days after treatment in the stented group for histomorphometric or immunohistochemical analysis.', 'Intracoronary PDT significantly reduced intimal thickness in both BI and stented arteries (about 65%: 0.22 (SEM 0.05) mm v 0.62 (0.05) mm, p < 0.01; and about 26%: 0.40 (0.04) mm v 0.54 (0.04) mm, p < 0.01, respectively). PDT increased luminal area by <or= 60% and 50% within BI and stented arteries (3.43 (0.27) mm(2)v 5.51 (0.52) mm(2), p < 0.05; 4.0 (0.02) mm(2)v 6.0 (0.16) mm(2), p < 0.01), respectively. Complete re-endothelialisation was observed by immunohistochemical and gross histological analyses in all PDT and control arteries. There were no cases of aneurysm formation or thrombosis.",
            "output": [
                "Does intracoronary photodynamic therapy reduce neointimal growth without suppressing re-endothelialisation in a porcine model?"
            ]
        },
        {
            "id": "task847-533efe76d5f4421280228b1ca5238d0c",
            "input": "This study was designed to evaluate the effects of a dorzolamide-timolol combination or dorzolamide on retinal ganglion cell (RGC) density and intraocular pressure (IOP) in glaucomatous eyes of adult rats.', 'Glaucoma was induced in the right eye of adult Wistar rats by episcleral venous occlusion. One experimental group was administered dorzolamide 2%-timolol 0.5% combination eye drops, while the other experimental group was administered dorzolamide 2% eye drops. Control groups had surgery without drug administration. Drug application was initiated either 2 weeks before surgery (Group A), from the day of surgery (Group B), 2 weeks after surgery (Group C), or 4 weeks after surgery (Group D). RGCs were labeled by intratectal Fluorogold injections and counted from flat-mount preparations, and IOP was measured using Tonopen.', 'Both dorzolamide-timolol combination and dorzolamide, when applied topically, significantly reduced IOP and improved RGC densities in experimental eyes when compared to control eyes. Earlier initiation, as well as longer duration of drug application, resulted in higher RGC densities.",
            "output": [
                "Does dorzolamide and timolol save retinal ganglion cells in glaucomatous adult rats?"
            ]
        },
        {
            "id": "task847-28b6d53c9086426fbda14e7ac661897a",
            "input": "The p16 gene is one of the tumor suppressor genes, and its inactivation results in abnormal regulation of the cell cycle in human neoplasms. Promoter hypermethylation, a mechanism of p16 gene inactivation, has been reported to play an important role in tumorigenesis and to be related to patient prognosis in several carcinomas.', 'To determine the role of the p16 gene in extrahepatic bile duct (EBD) carcinomas.', 'We examined promoter hypermethylation of the p16 gene using a methylation-specific polymerase chain reaction and the expression of the p16 protein using an immunohistochemical staining method in 90 cases of EBD carcinomas. We then compared the data with various clinicopathologic parameters, including survival rate.', 'Promoter hypermethylation was observed in 69 (77%) of the 90 cases. Of 69 hypermethylated cases, 32 (46%) demonstrated loss of p16 expression. Promoter hypermethylation of the p16 gene was more commonly observed in tumors with vascular invasion (22 [92%] of 24 cases) than without vascular invasion (71%, P = .03). Furthermore, p16 promoter hypermethylation with loss of p16 expression was more frequently observed in cases with lymph node metastasis (P = .006) and higher tumor stage group (P = .04). However, there was no significant difference in survival rate according to the status of p16 promoter methylation and/or p16 expression.",
            "output": [
                "Is promoter hypermethylation of the p16 gene and loss of its protein expression correlated with tumor progression in extrahepatic bile duct carcinomas?"
            ]
        },
        {
            "id": "task847-003971badbb74660aab7555840a94b10",
            "input": "Atopic dermatitis (AD) often develops in infancy as the first manifestation of the atopic phenotype. Wheezing is also common in infancy, but it is less clear whether infant wheezing should be considered as an atopic phenotype. If infant wheeze and AD share a common aetiology, this would indicate that infant wheezing is an atopic phenotype.', 'To investigate whether potential risk factors for infant wheeze and AD have similar effects on these 2 phenotypes, indicating a common etiology.', 'A total of 34.793 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, and prenatal, perinatal, and postnatal risk factors was collected by interview at 12 and 30 weeks of gestation, at 6 and 18 months of age, and by linkage to the Danish Medical Birth Register. Data were analyzed by binary and polytomous logistic regression models.', 'The following variables had significantly differential effects on infant wheezing and AD: parental hay fever, parental asthma, parental AD, sex, maternal age, maternal occupation, smoking during pregnancy, season of birth, birth weight, gestational age, head circumference, breast-feeding, number of older siblings, day care attendance, and pets in the home.",
            "output": [
                "Do differential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology?"
            ]
        },
        {
            "id": "task847-55d25da475ed4c718bb831af04c69b29",
            "input": "The administration of selective cyclooxygenase-2 inhibitors before surgery is regarded as an innovative option to manage postoperative pain. This study was designed to (1) examine the efficacy of preoperative cyclooxygenase-2 blockade on postoperative oral pain and (2) compare pain intensity with prostaglandin E2 (PGE2) production and cyclooxygenase isoform (cyclooxygenase-1, cyclooxygenase-2) messenger RNA (mRNA) expression at the surgical site during the postoperative period.', 'Sixty patients with impacted lower third molars were randomly allocated to three single-dose treatment groups--placebo, 50 mg rofecoxib, or 550 mg naproxen--1 h before extraction. Pain intensity was evaluated with categorical and visual analog scales every 30 min from 90 to 240 min after surgery. At these times, PGE2 production in the alveolar socket was also evaluated. Cyclooxygenase-1 and cyclooxygenase-2 mRNA expression was examined by reverse-transcription polymerase chain reaction in gingival specimens collected during tooth removal and 240 min after surgery.', 'Pain intensity and PGE2 production in the placebo group increased throughout the observation period. Naproxen prevented pain and decreased PGE2 release at all time points. Rofecoxib reduced PGE2 production versus placebo from 150 min onward, while inducing analgesia through the whole observation period. mRNA assay in gingival specimens collected at tooth extraction revealed cyclooxygenase-1 expression, whereas cyclooxygenase 2 was undetectable. At the end of observation, cyclooxygenase-1 mRNA expression was unchanged, whereas cyclooxygenase-2 mRNA was significantly induced.",
            "output": [
                "Does cyclooxygenase-2 induction after oral surgery entirely account for analgesia after selective blockade of cyclooxygenase 2 in the preoperative period?"
            ]
        },
        {
            "id": "task847-816be0ecc05846a7995ff36240a0b13a",
            "input": "PS-341 (bortezomib, Velcade), the first proteasome inhibitor approved by the Food and Drug Administration for the treatment of patients with relapsed multiple myeloma, induces apoptosis in human cancer cell lines. Vitamin C (ascorbic acid) is an essential water-soluble vitamin required for many normal physiologic functions and has to be obtained through diet or supplemental tablets in humans. Here we studied the potential effect of vitamin C on the anticancer activity of PS-341 in human cancer cell lines.', 'The effects of vitamin C on apoptosis induction by PS-341 alone and by PS-341 combined with tumor necrosis factor-related apoptosis-inducing ligand were studied. In addition, the effects of vitamin C and other antioxidants on PS-341-mediated proteasome inhibition were also examined. Finally, the direct chemical interaction between vitamin C and PS-341 was determined.', 'Vitamin C abrogated the ability of PS-341 to induce apoptosis in various human cancer cell lines, to induce G(2)-M arrest, and to augment apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand. Moreover, vitamin C suppressed PS-341-mediated inhibition of proteasome activity. PS-341 itself did not induce generation of intracellular reactive oxygen species whereas other antioxidants failed to abrogate its biological activity. Importantly, we detected a direct chemical interaction between vitamin C and PS-341.",
            "output": [
                "Does vitamin C inactivate the proteasome inhibitor PS-341 in human cancer cells?"
            ]
        },
        {
            "id": "task847-e2a6fca9047c4e2080e9326673bc0554",
            "input": "We investigated the effects of neutrophil elastase inhibitor ONO-5046 Na on lung ischemia-reperfusion injury in a canine model of single lung transplantation.', '24 mongrel dogs, 12 donors and 12 recipients, were used for single lung transplantation. Lung grafts were preserved for 18 h by cold ischemia then transplanted into the left thoracic cavity of recipients. In 6 recipients (ONO group), a bolus of ONO-5046 Na (10 mg/kg) was introduced before reperfusion and followed by continuous infusion (10 mg/kg/h). The remaining 6 recipients (control group) did not receive ONO-5046 Na and thus served as controls. We evaluated lung function and respiratory parameters over 240 min.', 'The total cell number in bronchoalveolar lavage fluid increased significantly in the control group in comparison to that in the ONO group. Histologic scores after 4 h of reperfusion and myeloperoxidase activity were significantly lower in the ONO group than in the control group.",
            "output": [
                "Does neutrophil elastase inhibitor ameliorate reperfusion injury in a canine model of lung transplantation?"
            ]
        },
        {
            "id": "task847-a48fac0890604600908947bb2d7b053a",
            "input": "There have been only a few structural brain-imaging studies, with varied findings, of opiate-dependent subjects. Voxel-based morphometry (VBM) is suitable for studying whole brain-wise structural brain changes in opiate-dependent subjects.', 'The objective of the current study is to explore gray matter density in opiate-dependent subjects.', 'Gray matter density in 63 opiate-dependent subjects and 46 age- and sex-matched healthy comparison subjects was compared using VBM.', 'Relative to healthy comparison subjects, opiate-dependent subjects exhibited decreased gray matter density in bilateral prefrontal cortex [Brodmann areas (BA) 8, 9, 10, 11, and 47], bilateral insula (BA 13), bilateral superior temporal cortex (BA 21 and 38), left fusiform cortex (BA 37), and right uncus (BA 28).",
            "output": [
                "Does prefrontal and temporal gray matter density decrease in opiate dependence?"
            ]
        },
        {
            "id": "task847-9bb382fb78304c1f8ee3b834bd09a24e",
            "input": "The association between serum uric acid (UA) and the prevalence of hypertension, and the relationship between methylenetetrahydrofolate reductase (MTHFR) polymorphism and hypertension remains unclear. The aim of the present study was to investigate whether the C677T MTHFR mutation genotype (VV) is independently associated with the prevalence of hypertension or blood pressure (BP), and examined any interaction of MTHFR and UA with BP.', \"Participants were randomly selected from all residents (aged 40-69 years) in a rural county of Japan, and the data for the men (n=335) were analyzed. ;Hypertension' was defined as systolic BP >or=140 and/or diastolic BP >or=90 mmHg and/or being administered antihypertensive medication. Serum UA level was independently associated with the prevalence of hypertension (odds ratio (95% confidence interval) =2.7 (1.2-5.9), p=0.047) for the highest tertile of serum UA (>or=398.5 micromol/L (6.7 mg/dl)) vs that of the lowest tertile (<321.2 micromol/L (5.4 mg/dl)), but the MTHFR mutation was not independently associated with prevalence of hypertension or BP. No interaction of the MTHFR mutation and serum UA with BP was found.",
            "output": [
                "Is polymorphism of methylenetetrahydrofolate reductase gene ( C677T MTHFR ) a confounding factor of the relationship between serum uric acid level and the prevalence of hypertension in Japanese men?"
            ]
        },
        {
            "id": "task847-188c7f9b53a24aab81cb9d6d3a5d2458",
            "input": "The goal of the present study was to identify predictors of event-free survival in nonischemic dilated cardiomyopathy (NIDCM) patients after administration of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and beta-blockers.', \"The study group comprised 78 consecutive patients with NIDCM between 1997 and 2002. NIDCM was defined as ejection fraction (EF) <0.40 and left ventricular end-diastolic diameter (LVEDD) >55 mm on echocardiography and normal coronary angiography. The mean EF and LVEDD was 26.3 +/- 10.5%, and 62.9 +/- 7.1 mm, respectively. Patients were treated with optimal medical therapy including ACEI/ARBs and/or beta-blockers and followed up for 35.6 +/- 27.8 months. The primary endpoint was either cardiac death or hospitalization because of deterioration of heart failure. Cox's regression analysis was used to establish the association of age, sex, EF, LVEDD, left atrial diameter, cardiac index, pulmonary capillary wedge pressure, QRS duration, severity of mitral regurgitation, body mass index, New York Heart Association class and the presence of atrial fibrillation with these events. During follow-up, 23 patients reached the primary endpoint. In a multivariate analysis, EF (chi-square 5.74, p=0.0166), severity of mitral regurgitation (chi-square 12.31, p=0.0004), and QRS duration (chi-square 11.20, p=0.0008) remained significant predictors.",
            "output": [
                "Are prolonged QRS duration and severity of mitral regurgitation unfavorable prognostic markers of heart failure in patients with nonischemic dilated cardiomyopathy?"
            ]
        },
        {
            "id": "task847-5a5825161e5344f8af3ef85c553a80b8",
            "input": "The purpose of the study was to determine the prevalence of posttraumatic stress disorder (PTSD), posttraumatic stress symptoms (PTSS), and major depressive disorder (MDD) in parents of children with epilepsy.', 'Parents (77 mothers and 3 fathers) of children with epilepsy were administered the Structured Clinical Interview for DSM-IV (SCID), PTSD and MDD modules, and the General Health Questionnaire (GHQ).', 'The prevalence of both PTSD and MDD was 31.5%. Fifty-six percent (n = 14) of the participants with PTSD had a diagnosis of MDD. PTSD symptom clusters were very prevalent in the parents of children with epilepsy. Reexperiencing and arousal symptom clusters were more frequent (88.8 and 80% respectively) than the avoidance and numbing symptom cluster (32.5%).",
            "output": [
                "Is posttraumatic stress disorder and major depressive disorder common in parents of children with epilepsy?"
            ]
        },
        {
            "id": "task847-8c0535fa346d43c5b7e1703537a05136",
            "input": "Uric acid is a well known antioxidant; however, the relationship between serum uric acid levels and oxidative stress-caused disorders including cardiovascular diseases is not clear yet. Transthoracic Doppler echocardiographic measurement of coronary flow reserve is a useful tool to investigate coronary flow reserve and coronary microvascular functions. In this study, we investigated the possible association between serum uric acid concentrations and coronary flow reserve in healthy adults.', 'One hundred healthy volunteers with normal uric acid levels, between 18 and 55 years of age, were included in this study. The study group was divided into two with regard to the serum uric acid levels. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion (0.56 mg/kg over 4 min) using echocardiography.', 'Coronary flow reserve and hyperemic mean peak flow velocity were significantly greater in participants with lower serum uric acid concentrations (< or =234 micromol/l for women, < or =302 micromol/l for men) than in those with higher serum uric acid concentrations (>234 micromol/l for women, >302 micromol/l for men) (2.91+/-0.5 vs. 2.47+/-0.5, P<0.001; 66.8+/-11.4 vs. 61.1+/-16.5, P=0.04). The baseline mean peak flow velocity was significantly greater in participants with higher serum uric acid concentrations than in those with lower serum uric acid concentrations (24.7+/-4.1 vs. 23.1+/-2.4, P=0.02).",
            "output": [
                "Are coronary flow reserve and coronary microvascular functions strongly related to serum uric acid concentrations in healthy adults?"
            ]
        },
        {
            "id": "task847-659e31976e8541bebeafb2d831cf026f",
            "input": "Whole-grain intake has been inversely associated with the metabolic syndrome in middle-aged populations, but the association has not been investigated in older adults. The metabolic consequence of consuming high whole-grain diets may differ in elderly persons, who are prone to greater insulin resistance and impaired glucose tolerance.', 'The aim of the present study was to examine the cross-sectional association between whole- and refined-grain intake, cardiovascular disease risk factors, prevalence of the metabolic syndrome, and the incidence of cardiovascular disease mortality in the same cohort of older adults.', 'The nutritional status of 535 healthy persons aged 60-98 y was determined from 1981 to 1984. The subjects kept a 3-d food record and had their blood tested for metabolic risk factors. The metabolic syndrome was defined based on criteria set by the third report of the National Cholesterol Education Program. The vital status of the subjects was identified in October 1995.', 'The results showed a significant inverse trend between whole-grain intake and the metabolic syndrome (P for trend = 0.005) and mortality from cardiovascular disease (P for trend = 0.04), independent of demographic, lifestyle, and dietary factors. Fasting glucose concentrations and body mass index decreased across increasing quartile categories of whole-grain intake (P for trend = 0.01 and 0.03, respectively), independent of confounders, whereas intake of refined grain was positively associated with higher fasting glucose concentrations (P for trend = 0.04) and a higher prevalence of the metabolic syndrome (P for trend = 0.01).",
            "output": [
                "Is whole-grain intake inversely associated with the metabolic syndrome and mortality in older adults?"
            ]
        },
        {
            "id": "task847-305af8e7f15e46fd8bcae58378cac454",
            "input": "Raised levels of plasma cell-free DNA have been detected in various patient groups, including trauma patients. We hypothesized that plasma DNA is increased in burn patients and may represent an objective indicator of burn severity and have predictive as well as prognostic significance.', 'This was a prospective clinical study with full ethical approval. With informed consent, blood samples were collected from 28 burn patients within 24 h of injury and from 12 control subjects. Plasma cell-free DNA was measured by real-time quantitative polymerase chain reaction (PCR) assay for the beta-globin gene. Descriptive analysis, non-parametric data comparison tests (Mann-Whitney) and correlation tests (Spearman rank) were performed on the data.', 'Samples were taken at a mean time of 5.7 h after injury from 13 patients with flame/flash burns and 15 patients with scalds. Median plasma DNA levels in the control, scald and flame/flash burn patient groups were 287, 648 and 2685 kilogenome-equivalents/L, respectively. Plasma DNA levels correlated with the length of hospital stay, but not with admission to the intensive care unit (ICU) nor the length of ICU stay. DNA levels correlated with the burn surface area (Spearman rank r = 0.54, p = 0.04) and the number of operations needed (Spearman rank r = 0.55, p = 0.03) for scalds, but not for flame/flash burns.",
            "output": [
                "Do plasma cell-free DNA as an indicator of severity of injury in burn patients?"
            ]
        },
        {
            "id": "task847-6d33d43ad7404a0284a5248241f8bcc1",
            "input": "Systemic activation of hemostasis and fibrolysis has been shown to be related to tumor progression in patients with malignancies such as lung cancer and colorectal cancer, but there has been no report of these clotting abnormalities in esophageal cancer. We investigated the clinical importance of measuring plasma levels of D-dimer (DD), which is a marker of the hypercoagulable stage, in preoperative patients with esophageal cancer.', 'Preoperative plasma DD levels were measured in 96 patients with primary esophageal cancer who were scheduled for esophagectomy with lymphadenectomy without preoperative treatment at our hospital. Results were correlated with the clinicopathological findings.', 'Significantly different plasma DD levels were found with respect to histologic T (p = 0.0015), histologic N (p < 0.0001), number of metastatic nodes (p < 0.0001), and histologic stages (p < 0.0001). The number of lymph node metastases (0/1 to 3/4 to 7/8-) was found to have the strongest association with DD level among the significant clinicopathologic factors (Spearman rank correlation 0.591, p < 0.0001). The most useful cut-off level of the plasma DD levels for diagnosis of lymph node metastasis was determined to be 0.4 microg/mL, with specificity and sensitivity for lymph node metastasis being 62.9% and 88.2%, respectively.",
            "output": [
                "Do plasma D-dimer levels show correlation with number of lymph node metastases in patients with esophageal cancer?"
            ]
        },
        {
            "id": "task847-a08a5ed7c3454e41b1411d0fb46f75fb",
            "input": "Carbamazepine is a commonly used anticonvulsant agent; however, it has been linked with various blood cell abnormalities. This study evaluated the effect of low-dose folic acid supplementation on the prevention of carbamazepine-induced hematological derangements in children.', 'This randomized clinical trial was conducted in children with epilepsy who received carbamazepine monotherapy. Group 1 received carbamazepine alone, and group 2 received carbamazepine plus folic acid. The two groups were age- and sex-matched. Each group comprised 41 children with epilepsy. Complete blood counts were obtained before starting medication (baseline) and then serially. The patients were followed for at least 1 year.', 'In group 1, 31.4% of the patients developed leukopenia and 17.1% neutropenia, but in group 2, these figures were 14.6 and 9.8% (P = 0.067 and P = 0.331, respectively). At the end of the first year of follow up, white blood cell and polymorphonuclear cell counts were significantly higher in group 2 (P = 0.007 and P = 0.001, respectively). Hemoglobin concentration dropped in group 1, but rose slightly in group 2; these changes were significant. Platelet, lymphocyte, and monocyte counts and changes in serial blood tests did not differ significantly between the two groups.",
            "output": [
                "Does folic acid supplementation reduce the development of some blood cell abnormalities in children receiving carbamazepine?"
            ]
        },
        {
            "id": "task847-2eb70d1f782546eab7e7dba567c87a90",
            "input": "An association between cow's milk hypersensitivity (CMH) and gastro-oesophageal reflux disease (GERD) in childhood has been reported in the past decade.\", \"To assess whether biopsies from the upper gastrointestinal tract of children with cow's milk sensitive GERD have a specific allergic inflammatory pattern, and to compare two different techniques for measuring inflammatory cells in gastrointestinal biopsies.\", \"GERD was diagnosed by means of endoscopy and oesophageal pH monitoring. Hypersensitivity to cow's milk was determined by an elimination diet and cow's milk challenge. Allergic inflammatory cells in upper gastrointestinal biopsies were identified by immunohistochemistry and their numbers were assessed by two different methods-counting the number of cells/high power field and using the computerised Cast-Grid system.\", \"Cow's milk sensitive GERD was identified in 10 of 17 children with severe GERD (median age, 7.8 years). Biopsies from children with endoscopic oesophagitis had significantly increased numbers of mast cells and T cells. No differences in the number of eosinophils, mast cells, or T cells were found between children with CMH and those with primary GERD. Several differences were found between the two different histological quantification methods.",
            "output": [
                "Is eosinophilia in the upper gastrointestinal tract a characteristic feature in cow 's milk sensitive gastro-oesophageal reflux disease . Measurement by two methodologies?"
            ]
        },
        {
            "id": "task847-b672f3e7fce244d093ae379d7d167280",
            "input": "To assess the possible influence of white-coat hypertension (WCH) on coronary flow reserve (CFR).', 'CFR was measured by means of transthoracic second harmonic Doppler echocardiography in 29 patients with WCH, 32 patients with sustained hypertension and 35 healthy volunteers.', 'CFR was significantly lower in the sustained hypertension group than in the WCH and the control groups, but it was not different between the WCH and the control groups (2.40 (SD 0.54), 2.77 (0.41) and 2.83 (0.60), respectively).",
            "output": [
                "Is coronary flow reserve preserved in white-coat hypertension?"
            ]
        },
        {
            "id": "task847-acf9ffe3b517403b9a42237aefcbedc6",
            "input": "To derive a nomogram of fetal maxillary bone length (MAX) for a Chinese population and to study whether first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) is an independent predictor of fetal MAX.', 'This was a prospective observational study over 10 months examining Chinese women with a singleton pregnancy who attended the first-trimester screening program for Down syndrome. The subjects had the fetal crown-rump length (CRL), nuchal translucency, MAX, maternal serum PAPP-A and free beta-human chorionic gonadotropin (fbeta-hCG) levels measured. A nomogram of MAX was derived using normal pregnancies with reliable dates. The correlations between MAX, CRL, PAPP-A and fbeta-hCG levels were studied, after correction for gestational dependency using Z-score transformation for the ultrasound markers (Z-MAX and Z-CRL), and logarithmic transformation of multiple of gestation-specific medians for the biochemical markers (log10PAPP-A multiples of the median (MoM) and log10fbeta-hCG MoM), using the Pearson test and multiple regression analysis.', 'During the study period, 607 Chinese women met the inclusion criteria. The mean gestational age at the first-trimester screening was 12 + 4 weeks (SD, 4 days). Curve estimation analysis showed that a linear relationship fit best between MAX and CRL (MAX (mm) = -0.01 + 0.101 * CRL (mm); r = 0.826; P < 0.0001), and between MAX and gestational age (MAX (mm) = -8.465 + 0.170 * gestational age (day); r = 0.754; SD = 0.71; P < 0.0001). There were significant positive correlations between Z-MAX and Z-CRL (r = 0.627; P = < 0.0001), Z-MAX and log10PAPP-A MoM (r = 0.239; P = < 0.0001). Multiple regression analysis showed that both Z-CRL (P = < 0.0001) and log10 PAPP-A MoM (P = 0.048) were independent predictors for Z-MAX.",
            "output": [
                "Is first-trimester maternal serum level of pregnancy-associated plasma protein-A an independent predictor of fetal maxillary bone length?"
            ]
        },
        {
            "id": "task847-39c127bd7df240f1ad14108b64277ac7",
            "input": "In the most recent version of the UICC TNM classification system for thyroid carcinoma, tumors with minimal extrathyroid extension were classified as T3. In this study, we investigated whether this upgrading is appropriate for papillary thyroid carcinoma.', 'We investigated the difference in the relapse-free survival (RFS) rate between patients with tumors having no, minimal, and massive extrathyroid extension in a series of 502 patients over the age of 45 years.', 'Patients with tumors showing massive extension showed a worse RFS rate except for those with tumors measuring 1 cm or less. However, there was no significant difference in RFS between tumors measuring 4 cm or less showing no or minimal extension. In an investigation of 409 patients without any clinically apparent node metastasis, the RFS of patients with tumors larger than 4 cm with massive extension was significantly worse than those with tumors measuring 4 cm or less, while the RFS of patients with tumors with either no or minimal extension did not depend on the tumor size.",
            "output": [
                "Does minimal extrathyroid extension affect the relapse-free survival of patients with papillary thyroid carcinoma measuring 4 cm or less over the age of 45 years?"
            ]
        },
        {
            "id": "task847-94d89cae07744ab693ba66b0c0b1ccb4",
            "input": "The human endometrium is an important site for contact between the host and pathogens ascending the reproductive tract, and thus plays an important role in female reproductive tract immunity. Previous work in our laboratory has suggested that Toll-like receptors (TLRs) are involved in endometrial epithelial recognition of pathogens and that ligation of endometrial TLRs results in the production of cytokines and chemokines important for both immune and reproductive functions of the endometrium. We have also demonstrated cyclic regulation of TLR3 mRNA and protein expression in human endometrium, suggesting that steroid hormones might play a role in the expression and function of TLR3. In this study, the effects of 17beta-estradiol (E2) and progesterone (P) on TLR3 expression and function in endometrial cell lines were investigated.', 'Endometrial epithelial cell lines were cultured and examined for the presence of TLR3 and hormone receptors by endpoint RT-PCR. For hormonal studies, cells were pre-treated with ethanol vehicle, 10(-8) M E2, and/or 10(-7) M P. For antagonist assays, cells were treated with the ER antagonist, ICI 182, 780, or the PR antagonist, RU486, for two hours prior to treatment with hormones. Following hormone or hormone/antagonist pre-treatment, cells were stimulated with vehicle, the synthetic TLR3 ligand, polyinosinic-polycytidylic acid (Poly I:C), a negative dsDNA control, or a positive control. Cytokine and chemokine production post-stimulation was measured by ELISA. The effects of E2 and P on TLR3 mRNA and protein expression were measured using Real Time RT-PCR and FACS analysis, respectively.', 'Stimulation of TLR3-expressing cells with the synthetic TLR3 ligand, Poly I:C, resulted in the production of cytokines and chemokines important for endometrial function and regulation. Suppression of Poly I:C-induced cytokine and chemokine production by cells treated with 10(-8) M E2, but not cells treated with 10(-7) M P, was observed in endometrial epithelial cell lines expressing TLR3 and estrogen receptor alpha (ERalpha). The effects of E2 were not observed on cells which did not express ERalpha or in cells pre-treated with the ER antagonist, ICI 182, 780. Treatment with E2 did not affect TLR3 mRNA or protein expression. However, treatment with E2 did suppress cytokine and chemokine production resulting from TLR3 stimulation with Poly I:C, suggesting that E2 modulates TLR3 function.",
            "output": [
                "Does 17Beta-estradiol suppress TLR3-induced cytokine and chemokine production in endometrial epithelial cells?"
            ]
        },
        {
            "id": "task847-c05d10d81fa2458a928785c37257daf0",
            "input": "Endothelial dysfunction has been found to be present in subjects with both small and medium-size blood vessel vasculitides. We assess whether endothelial dysfunction was also present in patients with biopsy-proven giant cell arteritis (GCA) and whether it might be improved following steroid treatment.', 'Endothelial function was determined in cross-sectional and longitudinal studies of 6 patients with biopsy-proven GCA diagnosed between January and May 2002 by measuring flow-mediated endothelial-dependent and independent vasodilatation (EDV and EIV) by brachial ultrasonography. Patients were assessed for endothelial function within 48 hours after the onset of steroid therapy, 4 weeks after the onset of steroid therapy, and 2 years after the disease diagnosis.', 'EDV was significantly impaired in patients with GCA compared with 12 matched controls [mean 2.9%, median 2.45% (range 2.1% to 4.7%) vs mean 6.5%, median 6.6% (range 3.9% to 9.3%) in matched controls; p = 0.002]. However, no significant difference existed between patients and controls in EIV. Significant improvement of EDV after the suppression of inflammation was achieved. At Week 4 after the onset of steroid therapy all 6 patients showed enhanced responses (p = 0.028). This improvement of EDV was still present when steroid treatment was ended, 2 years after diagnosis.",
            "output": [
                "Does steroid therapy improve endothelial function in patients with biopsy-proven giant cell arteritis?"
            ]
        },
        {
            "id": "task847-b1786e9a13d24354a4ec504d71fcb891",
            "input": "Approximately 1/3 of individuals have a high plasma response to dietary cholesterol (hyper-responders). Although increases in both LDL and HDL cholesterol have been observed, limited data exist regarding effects of egg consumption on lipoprotein subclasses and circulating carotenoids.', '29 postmenopausal women (50-68 y) and 13 men (60-80 y) were assigned to either 3 eggs (EGG, 640 mg cholesterol/d) or an equal volume of cholesterol-free egg substitute (SUB, 0 mg cholesterol/d) for 30 d. Following a 3 wk wash out, subjects crossed over to the alternate diet. Individuals with a response to dietary cholesterol > 2.2 mg/dL for each additional 100 mg of dietary cholesterol were classified as hyper-responders while hypo-responders were those with a response <or= to 2.2 mg/dL. Nuclear Magnetic Resonance (NMR) spectroscopy determined LDL and HDL size & particle concentrations. Dietary records were used to evaluate carotenoid consumption.', 'Hyper-responders had higher concentrations of both LDL (LDL-C) and HDL (HDL-C) cholesterol after EGG. In contrast, the concentrations of plasma LDL-C and HDL-C did not differ between the EGG and SUB for the hypo-responders. After EGG, hyper-responders had larger (>or= 21.2 nm) less atherogenic LDL particle (P < 0.001) and larger HDL particle (> 8.8 nm) (P < 0.01), with no significant difference in the total number of LDL or HDL particles. Regardless of response classification, all individuals had an increase in plasma lutein (from 32.4 +/- 15.2 to 46.4 +/- 23.3 ng/L) and zeaxanthin (from 8.8 +/- 4.8 to 10.7 +/- 5.8 ng/L) during EGG, yet hyper-responders displayed higher concentrations of carotenoids when compared to hypo-responders",
            "output": [
                "Are plasma LDL and HDL characteristics and carotenoid content positively influenced by egg consumption in an elderly population?"
            ]
        },
        {
            "id": "task847-84225e2c464640aca03eb9cf22b6fd28",
            "input": "This study aimed at (1) comparing the prevalence of generalized hypermobility in patients with chronic fatigue syndrome (CFS) and healthy volunteers, (2) examining the clinical importance of generalized hypermobility in patients with CFS, and (3) examining whether knee proprioception is associated with hypermobility in patients with CFS.', 'Sixty-eight patients with CFS filled out two self-reported measures (for the assessment of symptom severity and disability), were questioned about muscle and joint pain, and were screened for generalized hypermobility. Afterward, the patients performed a knee repositioning test (assessment of knee proprioception), and it was examined whether or not they fulfilled the criteria for benign joint hypermobility syndrome (BJHS). Sixty-nine age- and sex-matched healthy volunteers were screened for generalized joint hypermobility and performed the same knee repositioning test.', 'Compared with the healthy volunteers (4.3%, 3/68), significantly more patients with CFS (20.6%, 14/69) fulfilled the criteria for generalized joint hypermobility (Fisher exact test, P < .004). No associations were found between generalized joint hypermobility and the self-reported measures (including pain severity) or knee proprioception (Spearman correlation analysis). Knee proprioception was similar in both groups (Mann-Whitney U = 1961, z = -1.745, P = .81). Forty patients with CFS (58.8%) fulfilled the criteria for BJHS.",
            "output": [
                "Is generalized joint hypermobility more common in chronic fatigue syndrome than in healthy control subjects?"
            ]
        },
        {
            "id": "task847-1ae0af0734784427b0c3f3cf5306a53e",
            "input": "To document potential mediating effects of the Activator-assisted spinal manipulative therapy (ASMT) on pain and hyperalgesia after acute intervertebral foramen (IVF) inflammation.', 'The IVF inflammation was mimicked by in vivo delivery of inflammatory soup directly into the L5 IVF in adult male Sprague-Dawley rats. Thermal hyperalgesia and mechanical allodynia were determined by the shortened latency of foot withdrawal to radiant heat and von Frey filament stimulation to the hind paw, respectively. Intracellular recordings were obtained in vitro from L5 dorsal root ganglion (DRG) somata. DRG inflammation was examined by observation of the appearance and hematoxylin and eosin staining. ASMT was applied to the spinous process of L4, L5, and L6. A series of 10 adjustments were initiated 24 hours after surgery and subsequently applied daily for 7 consecutive days and every other day during the second week.', '(1) ASMT applied on L5, L6, or L5 and L6 spinous process significantly reduced the severity and duration of thermal and mechanical hyperalgesia produced by the IVF inflammation. However, ASMT applied on L4 did not affect the response in rats with IVF inflammation or the controls; (2) electrophysiological studies showed that hyperexcitability of the DRG neurons produced by IVF inflammation was significantly reduced by ASMT; (3) pathological studies showed that manifestations of the DRG inflammation, such as the increased vascularization and satellitosis, were significantly reduced 2 to 3 weeks after ASMT.",
            "output": [
                "Does spinal manipulation reduce pain and hyperalgesia after lumbar intervertebral foramen inflammation in the rat?"
            ]
        },
        {
            "id": "task847-2fb2fefe23be49c0a1a6921f40f58db6",
            "input": "The purpose of this study is to determine whether chiropractic manipulation is associated with any measurable changes in the difference between the arterial blood pressures on the left and right before and after treatment in normotensive subjects.', 'A nonrandomized, matched pair, controlled clinical trial, with the treatment (manipulation) group and control (resting) group matched for age and sex, was performed in chiropractic student clinics in London, UK. The treatment group consisted of 35 new patients presenting to a single student chiropractor between the start of April 2003 and the end of August 2003. The control group consisted of 35 nonpatients matched for sex and age. The intervention was chiropractic manipulation. Preintervention and postintervention systolic and diastolic blood pressures were recorded in both arms through the use of a digital oscillometric sphygmomanometer.', \"A significant difference was found between the pre- and posttreatment blood pressure differences for systolic pressures (P = .01), but no significant difference was found in either set of control data or the treatment diastolic values. A significant difference was also found between the treatment and control group's preintervention systolic differences (P = .002), but not between the groups at any other time.",
            "output": [
                "Does chiropractic manipulation affect the difference between arterial systolic blood pressures on the left and right in normotensive subjects?"
            ]
        },
        {
            "id": "task847-701552f2f0b54cb0b2fea978260837e2",
            "input": "Silicosis features foci of inflammation where macrophages and lymphocytes precede and accompany fibroblast proliferation, alveolar epithelial hyperplasia, and increased deposition of connective tissue matrix material. In the mouse following silica inhalation there is recruitment of natural killer-, B-, and CD4+ and CD8+ lymphocytes to the alveolar spaces, enlargement of bronchial-associated lymphoid tissues (BALT), and aggregation of lymphocytes surrounding small airways and blood vessels. A substantial fraction of the recruited lung lymphocytes produce interferon-gamma (IFN-gamma), and IFN-gamma gene-deleted mice develop less silicosis than wild-type mice. Interleukin-12 (IL-12) is an important pathway for driving the adaptive immune response towards a TH1-like phenotype. We hypothesized that IL-12 might stimulate lymphocyte activation and the up-regulation of IFN-gamma, and consequently be an essential mediator for silicosis.', 'C57Bl/6 wild-type (WT) and IL-12 deficient (IL-12 KO) mice were exposed to sham-air or crystobalite silica (61 mg/m3) by inhalation for 5 hours/day for 12 days and then studied from 1 to 112 days after exposure. Mice exposed to sham-air had normal lung histology at all time points. WT mice exposed to titanium dioxide (72 mg/m3) showed pulmonary macrophage recruitment but no increase in lung collagen. Both WT and IL-12 KO mice exposed to silica showed similar progressive lung pathology, increased wet lung weight and increased total lung collagen (hydroxyproline). IL-12 p35 mRNA was not increased in either strain after silica exposure; IL-12 p40 mRNA was up-regulated after silica in WT mice and constitutively absent in the IL-12 KO mice. IL-18 mRNA was not increased after silica exposure. The expression of IL-15 (an important driver for innate immunity, Natural Killer cell activation, and IFN-gamma production) was abundant in air-exposed mice and was increased slightly in the lungs of mice with silicosis.",
            "output": [
                "Is interleukin-12 essential for silicosis in mice?"
            ]
        },
        {
            "id": "task847-dc0975e7a2fe40bca0476c2151f0c35d",
            "input": "P53 is a key protein which controls cell cycle arrest and apoptosis in response to DNA damage. Auto-antibodies against p53 have been detected in some cancer patients and also in patients with autoimmune diseases. In these patients, the main cause of anti-p53 antibody occurrence was considered to be increased intracellular p53 protein in cancer cells and autoreactive lymphocytes, respectively. Intracellular p53 also increases with cardiomyocyte apoptosis during heart failure and autoreactive lymphocytes play a role in the course of idiopathic dilated cardiomyopathy (IDC) and ischemic cardiomyopathy (ICM). Based on these observations, we hypothesized that anti-p53 antibody response may also occur in patients with heart failure due to ICM and IDC.', 'The aim of this study was to evaluate anti-p53 antibodies in the serum of patients with heart failure due to IDC and ICM.', '70 eligible patients with heart failure and severe left ventricular systolic dysfunction (mean fractional shortening 12.03 +/- 3.93%) were included in the study. The aetiology of heart failure was IDC in 26 patients and ICM in 44 patients, according to the angiographic and echocardiographic findings.', 'Anti-p53 antibodies were not detected in any of the patients.",
            "output": [
                "Do serum anti-p53 antibodies occur in patients with heart failure due to idiopathic dilated and ischemic cardiomyopathies?"
            ]
        },
        {
            "id": "task847-cb3bb046c80b4053adf7009bbdf72bcd",
            "input": "The conventional 12-lead electrocardiogram (cECG) derived from 10 electrodes using a cardiograph is the gold standard for diagnosing myocardial ischemia. This study tested the hypothesis that a new 5-electrode 12-lead vector-based ECG (EASI; Philips Medical Systems, formerly Hewlett Packard Co, Boeblingen, Germany) patient monitoring system is equivalent to cECG in diagnosing acute coronary syndromes (ACSs).', 'Electrocardiograms (EASI and cECG) were obtained in 203 patients with chest pain on admission and 4 to 8 hours later. Both types of ECGs were graded as ST-elevation myocardial infarction if at least 1 of the 2 consecutive recordings showed ST elevation more than 0.2 mV, as ACS if one or both showed ST elevation less than 0.2 mV, T-wave inversion, or ST depression. Otherwise, the ECG was graded negative.', 'Final diagnosis was identical in 177 patients (87%; 95% confidence interval [CI], 82%-91%; kappa = 0.81; SE = 0.035). ST-elevation myocardial infarction was correctly identified or excluded by EASI with a specificity of 94% (95% CI, 89%-97%) and a sensitivity of 93% (95% CI, 86%-97%; using cECG as the gold standard). Of 118 patients with enzyme elevations, an almost identical number (72 [61% by EASI] and 73 [62% by cECG]) had ST elevations. Both techniques were equivalent in predicting subsequent enzyme elevation (identical, 108/143; 75% of ACS and ST-elevation myocardial infarction ECGs by EASI and cECG). Thus, both ECG methods had exactly the same specificity of 59% (95% CI, 48%-69%) and sensitivity of 91% (95% CI, 85%-96%) for detecting myocardial injury.",
            "output": [
                "Is a vector-based , 5-electrode , 12-lead monitoring ECG ( EASI ) equivalent to conventional 12-lead ECG for diagnosis of acute coronary syndromes?"
            ]
        },
        {
            "id": "task847-e49c7adaf17e4ae697c69b402102d4fe",
            "input": "Ischemic preconditioning (IPC) elicits two distinct windows of cardioprotection, an early phase that lasts for 1-2 h and a delayed phase that lasts for 24-72 h. However, there is conflicting data as to how long the heart is resistant to IPC-induced cardioprotection after the initial protection wanes, leading to the demonstration of IPC-resistance. This resistance to IPC appears to be dependent on the timing of the next IPC stimulus, the species of animals used and the model studied. Furthermore, the mechanisms responsible IPC-resistance are unknown. It is also important to demonstrate therapeutic interventions that will produce cardioprotection during this period of IPC-resistance.', 'To examine potential mechanisms responsible for acute IPC-induced resistance, the NHE-1 inhibitor EMD 85131 (2-methyl-5-methylsulfonyl-1-(1-pyrrollyl)-benzoylguanidine), which exerts its effects via mechanisms distinct from IPC, and the K(ATP) channel opener bimakalim, which bypasses the signaling mechanisms of IPC to directly open K(ATP) channels, were examined in a canine model of IPC-resistance. One 10 min. IPC stimulus followed by 10 min. of reperfusion produced a significant reduction in IS/AAR compared to Control (7.1 +/- 2.6% versus 26.0 +/- 6.2%; P < 0.05). However, IPC did not significantly protect the myocardium if a 2 h reperfusion period occurred between the initial IPC stimulus and the subsequent prolonged (60 min) ischemic challenge (IS/AAR: 22.5 +/- 4.8%: P > 0.05). Furthermore, hearts treated with IPC followed by 2 h of reperfusion were resistant to an additional IPC stimulus administered just prior to the subsequent 60 min. occlusion period (IS/AAR: 22.9 +/- 3.2%: P > 0.05). In contrast, administration of the NHE-1 inhibitor EMD 85131 (IS/AAR: 7.4 +/- 2.5%: P < 0.05) or the K(ATP) channel opener bimakalim (IS/AAR: 11.8 +/- 2.4%: P < 0.05) both afforded significant cardioprotection when administered at 2 h of reperfusion in previously preconditioned canine hearts resistant to IPC.",
            "output": [
                "Do cardioprotective-mimetics reduce myocardial infarct size in animals resistant to ischemic preconditioning?"
            ]
        },
        {
            "id": "task847-ff2485980b5d448abd880da6e25f3712",
            "input": "It is still uncertain whether or not there is a difference between metoprolol and carvedilol for the treatment of congestive heart failure. We attempted to determine the difference between the two beta-blockers in terms of their antiadrenergic effect during exercise in patients with heart failure and their efficacy based on the baseline plasma brain natriuretic peptide concentration.', 'Fifty-three patients with mild to moderate heart failure with a radionuclide left ventricular ejection fraction <40% received open label metoprolol or carvedilol in a randomized fashion. The increase in the heart rate normalized to the increase in the plasma norepinephrine concentration during exercise, was calculated as an index of adrenergic responsiveness during exercise.', 'The increase in heart rate normalized by the increase in plasma norepinephrine concentration, decreased after the initiation of beta-blockers in the carvedilol group, but not in the metoprolol group. The change in cardiac function was more favorable for carvedilol than metoprolol in patients who exhibited a higher baseline brain natriuretic peptide concentration.",
            "output": [
                "Does carvedilol exert more potent antiadrenergic effect than metoprolol in heart failure?"
            ]
        },
        {
            "id": "task847-639f2d4ee5f04b929d7167288537edb6",
            "input": "Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution. However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far. Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women. We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.', 'In consecutive cross sectional studies conducted between 1985-1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany. NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data. Lung function was determined and COPD was defined by using the GOLD criteria. Chronic respiratory symptoms and possible confounders were defined by questionnaire data. Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.', 'The prevalence of COPD (GOLD stages 1-4) was 4.5%. COPD and pulmonary function were strongest affected by PM10 and traffic related exposure. A 7 microg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%-7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%-5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03-1.72) for COPD. Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06-3.02) than for those living farther away. Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.",
            "output": [
                "Are long-term air pollution exposure and living close to busy roads associated with COPD in women?"
            ]
        },
        {
            "id": "task847-2f42e32bcf5b449f90ca58050bc58672",
            "input": "To study if spontaneous contractions augmented by proteinase-activated receptor-2 (PAR-2)-activating peptide serine-leucine-isoleucine-glycine-arginine-leucine (SLIGRL) involve coactivation of membrane chemoceptors and are associated with expression of PAR-2 mRNA in non-pregnant and pregnant rat myometrium.', \"Non-pregnant, mid-pregnant, and late pregnant rat uterine horn and small intestine segments were snap-frozen in liquid nitrogen to determine PAR-2 mRNA levels by real time polymerase chain reaction (PCR). Uterine rings were used for isometric tension recording. Effect of SLIGRL (0.1 mM) on spontaneous contractions before and after exposure to ibuprofen (cyclooxygenase inhibitor, 1.0 microM), SQ-29548 (thromboxane A(2) receptor inhibitor, 1.0 microM), ketotifen (histamine 1 receptor inhibitor, 10 microM), WEB-2170BS (platelet-activating factor (PAF) receptor inhibitor, 10 microM), atropine (muscarinic receptor inhibitor, 0.1 microM), or ketanserin (serotonin receptor inhibitor, 10 microM) were compared. Paired t-test and one-way ANOVA followed by Dunnett's or Newman-Keuls post hoc tests were used for statistical analysis when appropriate.",
            "output": [
                "Does pAR-2 activating peptide-induced stimulation of pregnant rat myometrium contractile activity partly involve the other membrane receptors?"
            ]
        },
        {
            "id": "task847-3b746e1c59074a49a4d95b8a8f727fab",
            "input": "The aim of this study was to determine the sites of local recurrence following radical (R0) total mesorectal excision (TME) for rectal cancer in an effort to elucidate the reasons for recurrence.', 'Thirty-seven patients with recurrence following curative resection for rectal cancer were identified from a population of 880 patients operated on by surgeons trained in the TME procedure. Two radiologists independently examined 33 available computed tomograms and magnetic resonance images taken when the recurrence was detected.', 'Twenty-nine of the 33 recurrences were found in the lower two-thirds of the pelvis. Two recurrent tumours appeared to originate from lateral pelvic lymph nodes. Evidence of residual mesorectal fat was identified in 15 patients. Fourteen of the recurrent tumours originated from primary tumours in the upper rectum; all of these tumours recurred at the anastomosis and 12 of the 14 patients had evidence of residual mesorectal fat.",
            "output": [
                "Do radiological findings support lateral residual tumour as a major cause of local recurrence of rectal cancer?"
            ]
        },
        {
            "id": "task847-edf943ec709e4d46960374c1fa264b63",
            "input": "One of the two parental allelic genes may selectively be expressed, regulated by imprinting, X-inactivation or by other less known mechanisms. This study aims to reflect on such genetic mechanisms.', 'Slides from short term cultures or direct smears of blood, bone marrow and amniotic fluids were hybridized with FISH probes singly, combined or sequentially. Two to three hundred cells were examined from each preparation.",
            "output": [
                "Do biphasic chromatin structure and FISH signals in reflect intranuclear order?"
            ]
        },
        {
            "id": "task847-0c75041adbf24951a63c85e29db15285",
            "input": "The toxicity of anti-rheumatic gold compounds has limited their use and development, yet both the toxicological and therapeutic actions of these compounds remain unclear. In the current study, we tested the hypothesis that intracellular reactive oxygen species (ROS) induced by Au(I) or Au(III) compounds mediate their ability to suppress mitochondrial activity.', 'Human THP1 monocytes were exposed to HAuCl(4) x 3H(2)O (Au(III)), or the anti-rheumatic compounds auranofin (AF) or gold sodium thiomalate (GSTM) for 6-72 h, after which mitochondrial activity (succinate dehydrogenase) was measured. To assess the role of cellular redox status as a mediator of mitochondrial suppression, monocytes were pre-treated with a pro-oxidant (t-butyl hydroquinone, t-BHQ) or antioxidant (N-acetyl cysteine, NAC ). ROS levels were measured 0-24h post-gold addition to determine their role as mediators of mitochondrial activity suppression.', 'AF was the most potent inhibitor of mitochondrial activity, followed by Au(III) and GSTM. Only Au(III) induced intracellular ROS; no ROS formation was observed in response to AF or GSTM exposure. Although anti- and pro-oxidants had some effects on mitochondrial suppression of Au compounds, collectively the data do not support redox effects or ROS formation as major mediators of Au-compound mitochondrial suppression.",
            "output": [
                "Do gold-induced reactive oxygen species ( ROS ) mediate suppression of monocytic mitochondrial or secretory function?"
            ]
        },
        {
            "id": "task847-5afd2c8392304b48b993d0dce9ef80e1",
            "input": "Cisplatin is widely used as an antineoplastic agent since it is effective against a broad spectrum of different tumours. Nevertheless, it has several potential side effects affecting different organ systems and an overdose may lead to life-threatening complications and even death.', 'We report on a 46-year old woman with non-small cell lung cancer who accidentally received 225 mg/m2 of cisplatin, which was threefold the dose as scheduled, within a 3-day period. Two days later, the patient presented with hearing loss, severe nausea and vomiting, acute renal failure as well as elevated liver enzymes. In addition, she developed a severe myelodepression. After plasmapheresis on two consecutive days and vigorous supportive treatment, the toxicity-related symptoms improved and the patient recovered without any sequelae.",
            "output": [
                "Does plasmapheresis reverse all side-effects of a cisplatin overdose -- a case report and treatment recommendation?"
            ]
        },
        {
            "id": "task847-b678ee301d2e4fc9a72dda10b4c397c7",
            "input": "NADH fluorescence microscopy has been used as an index of the metabolic state of tissue but is associated with various obstacles such as low spatial resolution and quenching effects of blood pigments that prevent reliable monitoring of tissue bioenergetics. The objective of this study was to develop a system to monitor tissue bioenergetics in vivo using NADH fluorescence microscopy in the rat ileal mucosa.', 'Using an inverted microscope with an epifluorescence unit and an intensified charge-coupled device camera, NADH fluorescence images were visualized. Fluorescence intensity was measured of beta-NADH solutions at varying concentration (n = 6) and pH (n = 3) and in ex vivo (n = 6) and in vivo (n = 6) preparations of ileal mucosa of Sprague-Dawley rats anesthetized with isoflurane.', 'Intravital fluorescence microscopy reveals a map of the microcirculation that permits visualization of NADH fluorescence and intercapillary areas. The system was adjusted so a linear relationship between physiological concentrations of beta-NADH and fluorescence was achieved (r(2) = 0.98, p < .0001). Decreasing the pH of the solution had no effect on fluorescence intensity and fluorescence intensity in an anoxic ex vivo ileal segment was similar to that of the in vivo ileum after ischemia. Ischemia also resulted in spatial heterogeneity that was abolished by the addition of a 550-nm LP filter.",
            "output": [
                "Does high-resolution intravital NADH fluorescence microscopy allow measurements of tissue bioenergetics in rat ileal mucosa?"
            ]
        },
        {
            "id": "task847-4ae54554b045464a887a23f73805201d",
            "input": "Sepsis is a systemic inflammatory response to a bacterial infection. Inflammation may result in injury to the small bowel and an increase in translocation of bacteria and toxins across the mucosal barrier, which may contribute to the progression of sepsis. Microcirculatory perfusion or cytopathic hypoxia may cause impairment of tissue bioenergetics and injury in sepsis. The objective of this study was to determine if sepsis is associated with microcirculatory hypoperfusion and impaired tissue bioenergetics in the ileal mucosa.', 'Sprague-Dawley rats were randomized to cecal ligation and perforation (sepsis group, n = 12) or control group (n = 14) and received arterial and venous catheters and fluid resuscitation. Following 24 h, rats were anesthetized with isoflurane and the ileum was prepared for intravital microscopy. Images of NADH fluorescence, which is an index of tissue bioenergetics, central arterial diameter, red cell velocity, red cell flux, and average intercapillary area, were recorded in 6-9 villi in each rat.', 'Central arterial red cell flux (control 277 +/- 30 cell/s, sepsis 108 +/- 13 cells/s, p < .05), diameter (control 10.4 +/- 0.4 microm, sepsis 8.2 +/- 0.3 microm, p < .05) and red cell velocity (control 590 +/- 47 microm/s, sepsis 449 +/- 63 microm/s, p < .05) were decreased while average intercapillary area (control 815 +/- 171 microm(2), sepsis 1412 +/- 364 microm(2), p < .05) and NADH fluorescence (control 116 +/- 6 AIU, sepsis 154 +/- 9 AIU, p < .05) were increased at the villus tip in the sepsis group.",
            "output": [
                "Are tissue bioenergetics and microvascular perfusion impaired in rat ileal mucosa in normotensive sepsis?"
            ]
        },
        {
            "id": "task847-b4d41b9e59ca4bcca52dde1d23d5d16b",
            "input": "To investigate fasting and postprandial adiponectin levels in PWS patients as compared to obese and lean subjects and whether they could contribute to the pathogenesis of obesity in this syndrome.', 'We studied 7 patients with PWS, 16 obese patients and 42 lean subjects for the fasting study. From this group, we evaluated 7 patients with PWS, 7 age-sex-BMI-matched obese non-PWS patients and 7 age-sex-matched lean subjects before and after the administration of 3,139.5 kJ (750 kcal) of a standard liquid meal (53.2% carbohydrate, 30% fat, 16.7% protein) after an overnight fast. Blood samples were obtained every 15 min for the first hour and every 30 min thereafter until 6 h. Adiponectin, IGF-I, glucose, triglycerides, cholesterol, and insulin were measured.', 'Fasting plasma adiponectin levels were lower in PWS than in lean subjects (5.24+/-2.56 vs. 8.28+/-4.63 microg/ml, p=0.041) but higher than in obese patients (4.01+/-1.27 microg/ml, p=0.047). After the meal, adiponectin concentrations mildly decreased in PWS at time point 240 min, while in obese and lean subjects no changes were observed. However, 6-hour postprandial AUC for adiponectin was similar in all three groups.",
            "output": [
                "Are postprandial adiponectin levels unlikely to contribute to the pathogenesis of obesity in Prader-Willi syndrome?"
            ]
        },
        {
            "id": "task847-d0c577c62df54390a888b2b47858bb89",
            "input": "The factors that regulate the growth hormone (GH) response to physiological stimuli, such as exercise, are not fully understood. The aim of the present study is to determine whether age, body composition, measures of sprint performance or the metabolic response to a sprint are predictors of the GH response to sprint exercise in non-obese young men.', 'Twenty-seven healthy, non-obese males aged 18-32 years performed an all-out 30-second sprint on a cycle ergometer. Univariate linear regression analysis was employed to evaluate age-, BMI-, performance- and metabolic-dependent changes from pre-exercise to peak GH and integrated GH for 60 min after the sprint.', 'GH was elevated following the sprint (change in GH: 17.0 +/- 14.2 microg l(-1); integrated GH: 662 +/- 582 min microg l(-1)). Performance characteristics, the metabolic response to exercise and BMI were not significant predictors of the GH response to exercise. However, age emerged as a significant predictor of both integrated GH (beta = -0.547, p = 0.003) and change in GH (beta = -0.448, p = 0.019) after the sprint.",
            "output": [
                "Is age an important determinant of the growth hormone response to sprint exercise in non-obese young men?"
            ]
        },
        {
            "id": "task847-08813311616a4d91a777c2ff4afb8091",
            "input": "To determine whether concentrations of heart-type fatty acid binding protein (H-FABP) measured before hospital discharge predict critical cardiac events in patients with idiopathic dilated cardiomyopathy (DCM).', '92 consecutive patients with DCM were enrolled and followed up for four years.', 'Serum concentrations of H-FABP, brain natriuretic peptide (BNP), cardiac troponin T before hospital discharge and survival rate.', '23 patients died of cardiac causes, received a left ventricular assist device or underwent heart transplantation during the four-year follow up. Univariate analyses showed that New York Heart Association functional class, heart rate, ejection fraction, serum H-FABP and plasma BNP were significant variables. According to multivariate analysis, serum H-FABP and plasma BNP concentrations were independent predictors of critical cardiac events. Cardiac troponin T before hospital discharge was not a predictor. The area under the receiver operating characteristic curve for death from critical cardiac events was similar between H-FABP and BNP. Patients with an H-FABP concentration at or above the median (> or = 5.4 ng/ml) had a significantly lower survival rate than those below the median, according to analysis by log rank test (p < 0.0001). When combined with BNP concentration at or above the median (> or = 138 pg/ml), H-FABP below the median predicted the worst prognosis among the combinations.",
            "output": [
                "Is heart-type fatty acid binding protein a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy?"
            ]
        },
        {
            "id": "task847-f6b016656f86494da8423404b9e4d856",
            "input": "Because of the immunomodulatory effects of transfusion, we attempted to identify factors associated with blood product use and determine the association of transfusion quantity with postoperative infection.', 'We studied total perioperative transfusion of blood products for 15,592 cardiovascular operations performed from July 1998 to May 2003. Infection end points were septicemia/bacteremia (n=351, 2.2%) and superficial (n=353, 2.3%) and deep (n=212, 1.4%) sternal wound infections. Factors associated with blood product administration were used to form balancing scores to adjust for differences in patient characteristics among those receiving and not receiving blood products.', 'Fifty-five percent of patients received packed red blood cells (RBC), 21% received platelets, 13% got fresh frozen plasma (FFP), and 3% got cryoprecipitate. Factors associated with RBC use included older age, female gender, higher New York Heart Association class, lower hematocrit, reoperation, and longer cardiopulmonary bypass time--all indicative of higher-risk patients. The more RBC units transfused, the higher was the occurrence of septicemia/bacteremia (p < 0.0001) and superficial (p=0.0007) and deep (p < 0.0001) sternal wound infection. Use of FFP (septicemia/bacteremia) and platelets (septicemia/bacteremia and deep sternal wound infection) mitigated against this association only slightly.",
            "output": [
                "Does transfusion increase the risk of postoperative infection after cardiovascular surgery?"
            ]
        },
        {
            "id": "task847-55ab111c89764a9ea17a28a824b316d7",
            "input": "Metformin may benefit the macrovascular complications of diabetes independently of its conventional hypoglycemic effects. Accumulating evidence suggests that inflammatory processes participate in type 2 diabetes and its atherothrombotic manifestations. Therefore, this study examined the potential action of metformin as an inhibitor of pro-inflammatory responses in human vascular smooth muscle cells (SMCs), macrophages (Mphis), and endothelial cells (ECs).', 'Metformin dose-dependently inhibited IL-1beta-induced release of the pro-inflammatory cytokines IL-6 and IL-8 in ECs, SMCs, and Mphis. Investigation of potential signaling pathways demonstrated that metformin diminished IL-1beta-induced activation and nuclear translocation of nuclear factor-kappa B (NF-kappaB) in SMCs. Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity. To address the significance of the anti-inflammatory effects of a therapeutically relevant plasma concentration of metformin (20 micromol/L), we conducted experiments in ECs treated with high glucose. Pretreatment with metformin also decreased phosphorylation of Akt and protein kinase C (PKC) in ECs under these conditions.",
            "output": [
                "Does metformin inhibit proinflammatory responses and nuclear factor-kappaB in human vascular wall cells?"
            ]
        },
        {
            "id": "task847-933aaf1fdb41478e80d6449d33002b83",
            "input": "In food-restricted rats, leptin suppresses semistarvation-induced hyperactivity (SIH) and decreases exploratory behavior. Leptin ameliorates anxiety-related movement in ob/ob mice. In this study, we assessed the relationship between leptin and qualities of physical activity and restlessness in acute anorexia nervosa (AN).', 'Serum leptin, body mass index (BMI), % body fat, and self- and expert-ratings of qualities of physical activity and restlessness were assessed in 26 inpatients with acute AN. Accelerometry was also performed. Regression analyses were used to predict activity and restlessness using BMI, % body fat, and leptin levels as predictor variables.', 'Leptin levels significantly contributed to the prediction of all measures of activity and restlessness.",
            "output": [
                "Do physical activity and restlessness correlate with leptin levels in patients with adolescent anorexia nervosa?"
            ]
        },
        {
            "id": "task847-502b387c36ce4af18d490f2943d2c824",
            "input": "To investigate for the first time whether the plasma CXCL16 concentration is altered in coronary artery disease (CAD) patients.', 'Accumulating evidence suggests that the novel chemokine/scavenger receptor CXCL16/SR-PSOX is involved in the development of atherosclerosis and CAD.', 'Using ELISA we assessed the plasma CXCL16 concentration in 40 stable angina pectoris (SAP) patients, 17 unstable angina pectoris/non-ST-elevation myocardial infarction (UAP/non-STEMI) patients, 387 survivors of a first myocardial infarction (MI) and healthy control subjects (44 controls for SAP and UAP/non-STEMI patient groups and 387 controls for post-MI patients).', 'SAP patients exhibited significantly lower median CXCL16 levels (2111 pg/ml) than the corresponding control subjects (2678 pg/ml) (P=0.0012). UAP/non-STEMI patients also appeared to have lower CXCL16 levels (2192 pg/ml) compared with controls (NS). Patients investigated 3 months after MI tended (P=0.07) to have lower CXCL16 levels (2529 pg/ml) than the corresponding controls (2638 pg/ml). There were no significant correlations between CXCL16 levels and different measures of CAD severity determined by quantitative coronary angiography in post-MI patients. Neither patients nor controls exhibited significant correlations between CXCL16 levels and plasma lipoprotein fractions, inflammatory cytokines, C-reactive protein or numbers of inflammatory cells in peripheral blood.",
            "output": [
                "Is decreased plasma CXCL16/SR-PSOX concentration associated with coronary artery disease?"
            ]
        },
        {
            "id": "task847-27818c19e17d4492bb99fd76c4f913de",
            "input": "The methods used to communicate relevant outcomes in oncology to patients will likely influence treatment decisions. The purpose of this study was to examine the influence of three different methods of describing the efficacy of therapy on treatment decisions regarding management of metastatic colorectal cancer.', 'Participants reviewed a clinical scenario and randomly received one of three ways of describing efficacy of chemotherapy in metastatic colorectal cancer: (1) relative risk reduction, (2) tumor response rate, and (3) median overall survival. They received the same clinical scenario but were presented four treatment options: (1) observation and supportive care, (2) chemotherapy, (3) surgery, and (4) surgery and chemotherapy and the accompanying median overall survival estimate.', 'Participants included 102 preclinical medical students. In the first scenario, 85% chose chemotherapy in the relative risk reduction group, as did 88% of the tumor response rate group, but significantly fewer participants did so in the median overall survival group (35%; P < .001). In the second scenario, there was a significant difference in treatment preferences, with 4% of participants choosing observation/supportive care. None chose chemotherapy only, 19% chose surgery only, and 77% chose surgery plus chemotherapy (P < .001).",
            "output": [
                "Does method of presenting oncology treatment outcomes influence patient treatment decision-making in metastatic colorectal cancer?"
            ]
        },
        {
            "id": "task847-85e4e8aac325426ab5a71274ba94e7c6",
            "input": "Hepatic artery thrombosis is a rare but extremely troublesome condition after liver transplantation. Recently, urgent arterial revascularization has been used as rescue therapy, leading to improved graft and patient survivals. Hepatic artery ligation produces a progressive reduction in portal vein blood flow. Theoretically, a hyperemic response may be expected following hepatic artery reperfusion (hepatic artery buffer response, HABR). In this study, we tested the hypothesis that HABR can maintain adequate liver oxygenation after temporary liver dearterialization.', 'Seven dogs (19.7 +/- 1.2 kg) subjected to 60 minutes of hepatic artery occlusion were observed for 120 minutes thereafter. Systemic hemodynamics was evaluated through Swan-Ganz and arterial catheters, and splanchnic perfusion by portal vein and hepatic artery blood flows (PVBF and HABF) via an ultrasonic flowprobe. Liver enzymes (ALT and LDH) and systemic and hepatic oxygen delivery (DO2hepat) were calculated using standard formulae.', 'Hepatic artery occlusion induced a progressive reduction in PVBF and DO2hepat. A complete restoration of HABF after hepatic artery declamping was observed; however, the DO2hepat (33.3 +/- 5.9 to 16.5 +/- 5.9 mL/min) did not return to the baseline levels.",
            "output": [
                "Does hepatic arterial buffer response fail to restore hepatic oxygenation after temporary liver dearterialization in canines?"
            ]
        },
        {
            "id": "task847-80eea3023b9f40ffbcde66e54bce4257",
            "input": "To investigate the effect of CD40Ig upon acute rejection of rat liver transplants.', 'Thirty-two orthotopic liver transplants were performed using Lewis to BN rats with \"the two-cuff technique\". The rats were randomly divided into three groups. Group A served as controls (n = 10); group B (n = 11) and group C (n = 11); Lipofectamine2000-pcDNA3.1 or Lipofectamine2000-pcDNA3.1. CD40Ig complex was injected into Lewis portal vein ex vivo before cold storage of the liver. On the fifth day after transplantation, three rats in each group were killed to study the pathological changes and TUNEL immune histochemistry performed to examine CD40Ig expression. Lymphocytes were obtained from the spleen. The mixed lymphocyte reaction (MLR) was performed to determine tolerance and sheep anti-human immunoglobulin G (IgG)-FITC-labeled T cells counted by flow cytometry. Postoperative survival times of rats in each group were recorded. The pathological changes of dead rats were observed.', 'The mean survival times of group A and B were 11.00 +/- 4.28 and 12.75 +/- 5.57 days, respectively. There were serious acute rejections in allograft liver in groups A and B. Apoptosis index was 33.67 +/- 5.69 versus 39.00 +/- 5.29. Group C mean survival time was 41.25 +/- 13.70 days (P < .01). Immune histochemistry showed CD40Ig-positive elements in the allograft liver, which revealed light acute rejection and apoptosis index was 0.27 +/- 0.21 (P < .01). The part of the allografted liver in a dead rat showed light acute rejection while the others displayed chronic rejection. Recipients were specifically tolerant to donors in the MLR assay. The IgG-FITC-labeled T cells accounted for 11.57% of all T cells in group C.",
            "output": [
                "Does transfection of CD40Ig into liver prevent acute rejection in rat liver transplantation?"
            ]
        },
        {
            "id": "task847-93a46ba0d98343af88bcc8691d7c1eb3",
            "input": "The aim of this study was to determine the effect of basal insulin, alone or with a sensitizer, or a combination of oral agents on nontraditional risk factors for cardiovascular disease (CVD).', 'We randomized 57 patients with T2DM to either (1) continuous subcutaneous basal Lispro insulin at a single rate using an insulin pump (basal insulin) or (2) basal insulin and oral pioglitazone 30 mg daily (basal insulin +Pio) or (3) a sulfonylurea and metformin (SU+M). We measured glycosylated hemoglobin (HbA1c), plasma high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor-1 (PAI-1), 8-epi-prostaglandin F2 alpha (PGF2alpha), serum lipoprotein (a) [Lp (a)], and lipoprotein profile at baseline and after 20 weeks of treatment.', 'HbA1c decreased by >or=2% (P<.001) and to comparable levels (P=NS) in all groups. Despite improved glycemia, hsCRP did not change in any group, whereas plasma PAI-1 fell with basal insulin +Pio (P<.02) and SU+M (P<.01). PGF2alpha declined with basal insulin (P<.02) and SU+M (P<.001). High-density lipoprotein cholesterol (HDL-C) increased only with basal insulin +Pio (18.2%, P<.05). Lp (a) increased with basal insulin therapy alone (P<.01). Data were pooled from all groups to determine the overall effect of glycemic control-there was a significant (P<.001) decline in HbA1c, PAI-1, and PGF2alpha and an increase in HDL-C (P<.001). There was no correlation between HbA1c reduction and changes in these parameters.",
            "output": [
                "Do diabetes treatments have differential effects on nontraditional cardiovascular risk factors?"
            ]
        },
        {
            "id": "task847-7a3c033d15ef4e989245e590ce54e919",
            "input": "Private umbilical cord blood (UCB) banking after delivery has increased over the last decade. For adult/somatic stem cell research UCB is an essential source of stem cells and researchers question if the number of UCB samples for research might be reduced by private banking.', 'A survey among seven private blood banks in Germany and analysis and comparison of the number of UCB samples donated for research within the STEMMAT project with private blood banking were performed from 03/2003 to 06/2005 at the Frauenklinik (OB/GYN), Technical University Munich, Germany.', 'Within 27.5 months 1,551 UCB samples were collected for research purposes; the effective recruitment rate was higher than expectations at an effective 66.2 %. Private UCB banking [n = 24] was distributed among three cord blood banks [n = 16, 6 and 4]. The rate of private blood banking was 0.99 % for all deliveries, thus reducing the effective rate for research purpose by only 1.5 %.",
            "output": [
                "Does [ Private umbilical cord blood banking reduce the number of samples for scientific stem cell research ]?"
            ]
        },
        {
            "id": "task847-a4122ce600154380817d33199bf40e73",
            "input": "In diabetic patients, hyperglycemia may precipitate seizures, and in experimental diabetes, indications for an increased neuronal excitability have been found. In this study, the excitability of the motor cortex and conduction of the central motor pathways were studied in diabetic patients in relation to the glycemic level.', 'Using a double-blind study protocol, transcranial magnetic stimulation (TMS) was performed in five Type 1 diabetic patients during normo- and hyperglycemia, using a hyperglycemic clamp technique. Single and paired-pulse transcranial magnetic and single root stimulations were applied before and after 3 h of a fixed glucose level of 5 and 16 mmol/l. The percentage of change from baseline at the two glycemic levels was calculated and compared.', 'No difference in central motor conduction time was found comparing the change following normo- and hyperglycemia. Furthermore, no difference was observed for the changes in latency and amplitude following double stimulation with interstimulation intervals (ISIs) of 0-125 ms comparing normo- and hyperglycemia.",
            "output": [
                "Does motor cortical excitability remain unaffected of short-term hyperglycemia in Type 1 diabetic patients?"
            ]
        },
        {
            "id": "task847-97ebfb6167b54d45a64390d9adeb332b",
            "input": "This study was undertaken to test the hypothesis that specific meal and snack patterns are associated with selected nutrient intakes in US adults.', 'Using the 24-hour dietary recall from the Third National Health and Nutrition Examination Survey, meal and snack patterns were described in relation to nutrient intakes.', 'The study included US adults aged 20 years or older (n=15,978).', 'All statistical analyses accounted for the survey design and sample weights. Linear regression analyses controlled for confounding factors, including energy intakes. Wald F tests were used for determination of significance between means of nutrient intakes by daily eating frequency or meal pattern groups.', 'Daily eating frequency was positively related to carbohydrate, folic acid, vitamin C, calcium, magnesium, iron, potassium, and fiber intakes and inversely related to protein, total fat, cholesterol, and sodium intakes. Meal patterns were further categorized into the five most commonly reported meal and snack combinations by population percentages including breakfast (B), lunch (L), dinner (D), and > or =2 snacks (S) (31.6%); B, L, D and 1 S (15.4%); B, D and > or =2 S (13.1%); B, L, D (8.3%); and L, D and > or =2 S (7.6%). Groups reporting B, L, D and 1 S and B, L, D and > or =2 S had the highest intakes of all micronutrients examined except cholesterol, vitamin B-6, and sodium. Breakfast skippers (L, D and > or =2 S) had the lowest intakes of all micronutrients examined except sodium.",
            "output": [
                "Are meal and snack patterns associated with dietary intake of energy and nutrients in US adults?"
            ]
        },
        {
            "id": "task847-dfcd075f41d840338cd9fc53b0235ad9",
            "input": "To examine if greater nutrition knowledge vs gains in knowledge promote more successful weight loss in low-income, overweight and obese mothers with young children.', 'A convenience sample of mothers and their children were measured for height and weight; mothers completed demographic and nutrition knowledge questionnaires pre- and post-intervention.', 'Participants (N=141) were recruited from government and public health clinics and elementary schools. Inclusion criteria for mothers were: family income <200% federal poverty level; overweight/obese; and Hispanic, African-American, or white race/ethnicity.', 'Eight weekly weight-loss classes emphasizing diet, physical activity, and behavior modification based on Social Cognitive Theory were administered to mothers.', 'Improvements in maternal nutrition knowledge and weight loss.', 'Paired-samples t tests, repeated measures analysis of variance, analysis of covariance, Pearson correlations, and chi(2) statistics.', 'Nutrition knowledge of mothers increased in all areas. Participants with weight loss > or =2.27 kg (responders) had greater knowledge than those who did not; however, the actual net gain was similar for those who lost and did not lose weight. Weight gainers only improved in two areas on the test, whereas weight-loss responders increased knowledge in all six. Responders appeared more cognizant of diet, weight loss, and health information.",
            "output": [
                "Is nutrition knowledge associated with greater weight loss in obese and overweight low-income mothers?"
            ]
        },
        {
            "id": "task847-b87417ae95854909bd16fe2da27e60e5",
            "input": "Increased rates of apoptosis have been reported to play a role in the pathophysiology of many disorders, including liver diseases. Conversely, genetic mutations that result in impairment of programmed cell death have been associated with cancer development. However, apoptosis resistance can also be the result of nongenetic stress adaptation, as seen in the cancer-prone metabolic liver disease hereditary tyrosinemia. To clarify whether stress-induced apoptosis resistance is a general feature of chronic liver diseases, an animal model of chronic cholestasis was examined.', 'Studies were performed with mice before and 2 weeks following bile duct ligation and with Fah-/- and Fah/p21-/- mice before and after NTBC withdrawal.', 'Here we show that bile duct ligation induced profound resistance against Fas monoclonal antibody-mediated hepatocyte death. The apoptosis signaling pathway was blocked downstream of caspase-8 activation and proximal to mitochondrial cytochrome c release. In controls, activation of the Fas receptor resulted in rapid dephosphorylation of Bid and its subsequent cleavage, whereas Bid remained phosphorylated and uncleaved in chronic cholestasis and other models of hepatic apoptosis resistance.",
            "output": [
                "Is sustained phosphorylation of Bid a marker for resistance to Fas-induced apoptosis during chronic liver diseases?"
            ]
        },
        {
            "id": "task847-fb22734afed84a6fb1e0ce6a34e98735",
            "input": "Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis.', 'We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (-871G and -336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations.",
            "output": [
                "Is promoter variation in the DC-SIGN-encoding gene CD209 associated with tuberculosis?"
            ]
        },
        {
            "id": "task847-45e5afbae9404e02880bcc1523c947c2",
            "input": "The ratio between urinary albumin concentration (UAC) and urinary creatinine concentration (UCC) is widely used to estimate renal involvement. We examined how UAC and UCC associate with each other, with other risk factors, and with diabetic complications in a population-based sample of Type 2 diabetic patients.', 'A freshly voided morning urine specimen was provided by 1,284 consecutive, newly diagnosed diabetic patients aged 40 years or over in general practice. Albumin was measured by a polyethyleneglycol radioimmunoassay and creatinine by a modified Jaffe method.', 'In a multivariate model including UAC, UCC, age, sex, HbA1c, and urinary glucose concentration, UAC increased with both age (P=.042) and HbA1c (P=.014), while UCC decreased (P<.001 and P<.001, respectively). In two regression models, the prevalence of diabetic retinopathy (P<.001) and relatively high resting heart rate (P<.001) increased with increasing UAC but decreased with increasing UCC (P=.002 and P=.005, respectively).",
            "output": [
                "Is urinary creatinine concentration inversely related to glycaemic control and the presence of some diabetic complications in patients with newly diagnosed Type 2 diabetes?"
            ]
        },
        {
            "id": "task847-a6ced8d97f5b4ff9b574ab23254b3c24",
            "input": "Presence of intratumoral T-cell infiltration has been linked to improved survival in ovarian cancer patients. We questioned whether antibody immunity specific for ovarian cancer tumor antigens would predict disease outcome. We evaluated humoral immune responses against ovarian cancer antigens p53, HER-2/neu, and topoisomerase IIalpha.', 'Serum was collected from 104 women (median age, 59 years; range, 34 to 89 years) at the time of their initial definitive surgery for ovarian cancer. Serum was analyzed by enzyme-linked immunosorbent assay for antibodies to p53, HER-2/neu, and topoisomerase IIalpha proteins. Antibody immunity to tetanus toxoid was assessed as a control. The incidence of humoral immunity at the time of diagnosis to any of these three antigens was tabulated. For patients with advanced-stage disease (III/IV), correlation was made between the presence of tumor-specific immunity at the time of diagnosis and overall survival. Patients were followed for a median of 1.8 years.', 'Multivariate analysis showed the presence of p53 antibodies to be an independent variable for prediction of overall survival in advanced-stage patients. Overall survival was significantly higher for patients with antibodies to p53 when compared with patients without p53 antibodies (P = .01). The median survival for p53 antibody-positive patients was 51 months (95% CI, 23.5 to 60.5 months) compared with 24 months (95% CI, 19.4 to 28.6 months) for patients without antibodies to p53.",
            "output": [
                "Is antibody immunity to the p53 oncogenic protein a prognostic indicator in ovarian cancer?"
            ]
        },
        {
            "id": "task847-09312b2b88d84be798276bde72fe8571",
            "input": "The aim of this study was to describe the revascularization process of autogenous bone block grafts placed with or without an expanded polytetrafluoroethylene (e-PTFE) membrane.', 'Thirty Wistar male rats had their mandibles augmented by either an autogenous bone block graft (group A) or an autogenous bone block graft covered with an e-PTFE membrane (group B). The animals were sacrificed by perfusion at baseline, 3, 7, 14, and 21 days after surgery.', 'After 3 days, the presence of vascular sprouts derived from the recipient bed was observed in group A; more discrete sprouts were also observed in group B. After 7 days, revascularization continued, with vessels derived from both the recipient bed and the surrounding connective tissue in group A but only from the recipient bed in group B. At 14 days, group A showed penetration of vessels at the periphery of the graft; the vessels reached varying distances inside it. In group B, revascularization of the graft occurred mainly near its perforation, its borders, and at the recipient bed-graft interface. After 21 days, graft vascular penetration could be observed throughout the extent of the graft in group A but only approximately halfway through the graft in group B.",
            "output": [
                "Does revascularization of autogenous block graft with or without an e-PTFE membrane?"
            ]
        },
        {
            "id": "task847-7ba40e604b4d4d4db3d47cd67d392ac0",
            "input": "Microbial leakage and colonization between implants and their abutments may cause inflammatory reactions in the peri-implant tissues. This study evaluated microbial leakage at the implant-abutment interface with a new in vitro model.', 'Bacterial leakage was tested during dynamic loading in a 2-axis chewing simulator. The authors theorized that dynamic loading would decrease the stability of the implant-abutment connections and thereby lead to bacterial penetration along the gap. Five different implant systems with 8 standard implant-abutment combinations for single molar crowns were tested. The internal aspects of the implants were inoculated with a bacterial suspension and connected to the superstructure with the recommended torque. The specimens were immersed in a nutrient solution and loaded with 1,200,000 cycles of 120 N in the chewing simulator.', 'Statistically significant differences (P < or = .05) between implant systems with respect to number of chewing cycles until bacterial penetration were found.",
            "output": [
                "Do in vitro evaluation of bacterial leakage along the implant-abutment interface of different implant systems?"
            ]
        },
        {
            "id": "task847-902a91b806b042c9b39043ab5dd483de",
            "input": "The aim of this study was to evaluate how closely analysis of bone quality performed using the bone mineral density (BMD) values obtained by quantitative computerized tomography (QCT) reflected the histologic bone density.', \"Eighteen patients requiring implant therapy underwent CT scanning. Their data were processed using Image Master software, and the BMD was calculated by measuring the Hounsfield units and relating those values to a phantom (Calibration Phantom, Quantitative Technologies). Each patient wore a radiographic-surgical template in which titanium cylinders were placed as a drilling guide for preparation of the implant site. The mouth regions where the titanium guides were placed (on the CT images and in the patient's mouth) corresponded to the implant sites where the BMD was measured and where tissue specimens for histomorphometric analysis retrieved. Forty specimens measuring 6 mm in length and 2 mm in diameter were obtained. Histomorphometric analysis was performed by digitizing the images, which were subsequently analyzed using the image analysis software IAS 2000. The bone volume (BV) was calculated as a percentage by dividing the area occupied by the mineralized bone over the entire microscopic field.\", 'The results of the statistical analysis showed a Pearson correlation coefficient of 0.691 between the BV and BMD values, with a P value < 0.01, which was considered significant.",
            "output": [
                "Are bone mineral density and bone histomorphometry statistically related?"
            ]
        },
        {
            "id": "task847-b5281c9104694c1abe071ea3dab6e13d",
            "input": "Mechanosensitive (MS) ion channels provide a mechanism for the perception of mechanical stimuli such as sound, touch, and osmotic pressure. The bacterial MS ion channel MscS opens in response to increased membrane tension and serves to protect against cellular lysis during osmotic downshock. MscS-like proteins are found widely in bacterial and archaeal species and have also been identified in fission yeast and plants. None of the eukaryotic members of the family have yet been characterized.', 'Here, we characterize two MscS-like (MSL) proteins from Arabidopsis thaliana, MSL2 and MSL3. MSL3 can rescue the osmotic-shock sensitivity of a bacterial mutant lacking MS-ion-channel activity, suggesting that it functions as a mechanosensitive ion channel. Arabidopsis plants harboring insertional mutations in both MSL3 and MSL2 show abnormalities in the size and shape of plastids, which are plant-specific endosymbiotic organelles responsible for photosynthesis, gravity perception, and numerous metabolic reactions. MSL2-GFP and MSL3-GFP are localized to discrete foci on the plastid envelope and colocalize with the plastid division protein AtMinE.",
            "output": [
                "Do mscS-like proteins control plastid size and shape in Arabidopsis thaliana?"
            ]
        },
        {
            "id": "task847-911a282a7393433892a7b8a1f409bc21",
            "input": "In patients with stroke, gradient-echo MRI commonly detects microbleeds, indicating small artery disease with increased risk of macroscopic intracranial bleeding. Antithrombotic treatments are frequently prescribed after TIA and stroke, but there have been no previous studies of microbleeds in TIA. Because microbleeds may predict the hemorrhagic risk of antithrombotic treatments, we studied the prevalence of microbleeds, risk factors, and pathophysiologic mechanisms in patients with ischemic stroke and TIA.', 'One hundred twenty-nine consecutive patients with ischemic stroke or TIA were studied with MRI including T2, fluid-attenuated inversion recovery, and gradient-echo MRI sequences. Blinded observers counted microbleeds and graded white matter T2 hyperintensities throughout the brain. TIA patients with previous ischemic stroke were excluded.', 'Sixty-seven percent of patients had ischemic stroke; 33% had TIA. Microbleeds were found in 23% of ischemic stroke patients but only 2% of TIA patients (p < 0.001). There were no significant differences in conventional risk factors or the severity of white matter disease on T2 MRI between stroke and TIA patients. Patients with microbleeds were more often hypertensive (81 vs 59%; p = 0.04) and had more severe MRI white matter disease on T2 MRI (p = 0.003).",
            "output": [
                "Are cerebral microbleeds common in ischemic stroke but rare in TIA?"
            ]
        },
        {
            "id": "task847-0ba127bb007a44d7a0f25c91d2170a20",
            "input": "Changes in high-frequency (HF) QRS components of the electrocardiogram (ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting perfusion defects during adenosine tetrofosmin myocardial perfusion imaging (MPI).', '12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium Tc 99m tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphologic score that incorporated the number, type, and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST-segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P < .001).",
            "output": [
                "Does high-frequency QRS electrocardiogram predict perfusion defects during myocardial perfusion imaging?"
            ]
        },
        {
            "id": "task847-9a7a458b90664cd2807bcd98061ac22e",
            "input": "The hormone melatonin regulates the sleep and this pineal hormone is synthesized in the organism from the amino acid tryptophan. It is known that breast-fed babies have better sleep patterns and a better entrained sleep/wake cycle than bottle-fed babies (adapted formula).', \"To compare the circadian rhythm of 6-sulfatoxymelatonin (aMT6s)--the metabolite of melatonin excreted in the urine--in urine of bottle-fed and breast-fed children, and relate it to the circadian rhythm of tryptophan in breast milk, also evaluating the possible effects on the baby's night-time rest.\", '16 infants of 12 weeks of age were studied, divided into two groups depending on their exclusively natural or artificial feeding. The circadian rhythm of 6-sulfatoxymelatonin in urine was measured for the two groups of infants and for the breast-feeding mothers. In the breast milk, the circadian rhythm of the amino acid tryptophan was measured. The rest of the infants was tested by wrist actimeters for a week and the sleep parameters of the infants were measured and evaluated.', 'The tryptophan in the breast milk presented a circadian rhythm with acrophase at around 03:00. This affected the 6-sulfatoxymelatonin circadian rhythm with acrophase at 06:00 in the breast-fed infants, and also promoted nocturnal sleep. Assumed sleep, actual sleep, and sleep efficiency were significantly increased in the breast fed infants with respect the formula fed infants.",
            "output": [
                "Does the circadian rhythm of tryptophan in breast milk affect the rhythms of 6-sulfatoxymelatonin and sleep in newborn?"
            ]
        },
        {
            "id": "task847-7e26f831196e4bd6b6f9a377016d245f",
            "input": "The necessity for general anesthesia represents an impediment to using a laparoscopic approach for some procedures that are otherwise performed with the patient under local anesthesia using a conventional open technique. Heating and humidifying the insufflation gas reportedly reduces perioperative pain associated with a CO2 pneumoperitoneum, thus enabling awake laparoscopy.', 'Two cases are reported herein of laparoscopy performed with the patient under local anesthesia using heated, humidified CO2 gas for the pneumoperitoneum.', 'Both patients experienced pain with insufflation of heated, humidified CO2 gas of sufficient magnitude that the procedure could not be performed. The CO2 gas was washed out and replaced with helium gas insufflation with complete resolution of pain. The laparoscopic procedures were accomplished without further discomfort with local anesthesia and using a helium gas pneumoperitoneum.",
            "output": [
                "Is heated , humidified CO2 gas unsatisfactory for awake laparoscopy?"
            ]
        },
        {
            "id": "task847-55b94f0c854147a2974c66d9db033d97",
            "input": "The recently discovered hormone resistin is linked to the development of insulin resistance, but direct evidence of resistin levels in humans with nonalcoholic fatty liver disease (NAFLD) is lacking.', 'We conducted this study to assess the relationship between serum resistin and NAFLD. We measured serum resistin and biochemical, hormonal, and histological correlates in 28 NAFLD patients, 33 controls, and 30 obese patients [body mass index (BMI), >30 kg/m2] without NAFLD.', 'Resistin and adiponectin expression were measured in sc adipose tissue by quantitative RT-PCR. Resistin was higher in NAFLD patients compared with controls (5.87 +/- 0.49 vs. 4.30 +/- 0.20 ng/ml; P = 0.002) and obese patients (4.37 +/- 0.27 ng/ml; P = 0.002). Increased resistin mRNA was also found in the adipose tissue of NAFLD patients compared with controls and obese subjects.",
            "output": [
                "Is increased serum resistin in nonalcoholic fatty liver disease related to liver disease severity and not to insulin resistance?"
            ]
        },
        {
            "id": "task847-c4ea8810f2884c1589c27d6e26fb95cf",
            "input": "While the U.S. elderly population uses a disproportionate amount of healthcare resources, there is limited knowledge from prospective studies regarding the impact of lifestyle-related factors on costs in this group. The association was examined between smoking, drinking, exercise, body mass index (BMI), and changes in these risk factors, and healthcare costs after 4 years among 68- to 95-year-olds.', 'A total of 1323 participants completed annual surveys providing information on lifestyle factors (1986-1994) and health utilization (1994-1998). Healthcare costs in nine categories were ascertained from validated utilization. The relationships between risk factors and costs were examined in 2004 using linear regression models.', 'Fewer cigarette pack-years and lower BMI were the most significant predictors of lower total costs in 1998 (p<0.001), controlling for baseline sociodemographic factors, costs, and conditions. Associations with smoking were strongest for hospitalizations, diagnostic tests, and physician and nursing-home visits. Those who reduced smoking by one pack per day experienced cost savings of 1160 dollars (p<0.05). The costs for normal weight compared to minimally obese seniors were approximately 1548 dollars lower, with diagnostic testing, physician visits, and medications accounting for much of this difference. Daily walking, measured at baseline, also predicted lower costs for hospitalizations and diagnostic testing.",
            "output": [
                "Do lifestyle risk factors predict healthcare costs in an aging cohort?"
            ]
        },
        {
            "id": "task847-968c01c2972f49b796ed0bdcf42dc006",
            "input": "In France, when physicians in ambulances take care of patients, they report medical status to the dispatch centre. Then the dispatching physician search for the available and appropriate hospital service to agree in directly receiving the patient. We attempted to evaluate this direct admission dispatch, in a urban area, with many health care facilities.', 'Prospective evaluation.', 'All the files for out of hospital interventions with a dispatch process were included. Data collected and analysed were: main pathologies, started time and end time of direct admission dispatch process and number of services called before finding the right place.', '959 patients files were included, 849 could be analysed. The average duration of direct admission dispatch process is 10 (+/-13) minutes. Traumatology speciality shows a longer dispatch process than medicine disease (p < 0.001), and this time increased during summer (p < 0.05). The other parameters did not influence this duration.",
            "output": [
                "Do [ Evaluation of duration for direct admission dispatch process in an urban area ]?"
            ]
        },
        {
            "id": "task847-e03497c5abac426fb43c4adafa9151ff",
            "input": "To determine whether pulmonary arterial hypertension (PAH) is a prognostic factor for mortality in diffuse cutaneous systemic sclerosis (dcSSc), independent of interstitial lung disease (ILD).', 'ILD was diagnosed by high-resolution computed tomography and PAH (pulmonary arterial systolic pressure [PASP] > or =45 mm Hg) by echocardiography. All patients with ILD underwent testing for total lung capacity (TLC), forced vital capacity (FVC), and diffusing capacity for carbon monoxide.', 'Eighty-six patients with dcSSc (mean age at diagnosis 44.5 years) were followed up for a median of 72.5 months. ILD was found in 52 patients (60%) and PAH in 18 (21%). ILD was associated with PAH in 15 patients. Seventeen patients died (19.8%), 9 of whom had PAH (P = 0.001) and 10 of whom had ILD (P = 0.99). By multivariate analysis, age at SSc diagnosis and PAH were the only independent predictors of death (hazard ratio [HR] 1.057, 95% confidence interval [95% CI] 1.009-1.109, P = 0.020 and HR 4.09, 95% CI 1.47-11.5, P = 0.007, respectively). Mean TLC and mean FVC were similar in ILD patients with and those without PAH (P = 0.71 and P = 0.40, respectively). Among ILD patients, age at SSc diagnosis and PAH were again the sole predictors of death (HR 1.073, 95% CI 1.003-1.149, P = 0.042 and HR 5.07, 95% CI 1.09-23.8, P = 0.038, respectively). Twenty ILD patients received at least 6 monthly pulses of intravenous cyclophosphamide (CYC). In CYC-treated patients with PAH (n = 8), PASP increased significantly during the CYC regimen (mean +/- SD 55 +/- 14.5 mm Hg; P = 0.015 versus baseline), while TLC remained stable during the same period.",
            "output": [
                "Is pulmonary arterial hypertension a major mortality factor in diffuse systemic sclerosis , independent of interstitial lung disease?"
            ]
        },
        {
            "id": "task847-32b5327905484b599b85cb0e2ea1c634",
            "input": "We have previously demonstrated that hypertonic saline (HS) resuscitation decreased inflammation and mucosal injury after mesenteric ischemia/reperfusion (I/R). In contrast to I/R cell necrosis, apoptosis provides controlled cell death that minimizes inflammation. We therefore hypothesized that HS resuscitation after mesenteric I/R would induce apoptosis and decrease mucosal injury.', \"Rats underwent 60 minutes of superior mesenteric artery occlusion (SMAO) and then received no resuscitation or resuscitation with 4 mL/kg of HS, 4 mL/kg of lactated Ringer's (LR) solution (equal volume), or 32 mL/kg of LR solution (equal salt load). Rats were killed at 6 hours of reperfusion, and ileum was harvested for analysis. DNA fragmentation (apoptosis) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and mucosal injury by histology (Chiu score 0-5). Caspase-3 (proapoptotic mediator) and Bcl-xL (antiapoptotic mediator) protein expression were analyzed by Western immunoblot.\", 'SMAO with no resuscitation, SMAO with 4 mL/kg of LR, and SMAO with 32 mL/kg of LR increased apoptosis (quantitated by TUNEL) and I/R-induced mucosal injury (quantitated by Chiu score). This was associated with an increase to similar levels in both proapoptotic caspase-3 and antiapoptotic Bcl-xL protein expression. Moreover, SMAO with 4 mL/kg of HS further increased apoptosis but decreased mucosal injury. This was associated with a differential expression of proapoptotic caspase-3 over antiapoptotic Bcl-xL.",
            "output": [
                "Does hypertonic saline resuscitation after mesenteric ischemia/reperfusion induce ileal apoptosis?"
            ]
        },
        {
            "id": "task847-28e85cbfa2804ffd90a3df3bc91b97d4",
            "input": "Preservation of mucosal immunity has been shown to affect the risk and outcome of pneumonia in severely injured patients. Secretory immunoglobulin A (SIgA) is the principle humoral defense of mucosal surfaces in the body and has several antiinflammatory properties. Polymorphonuclear neutrophils (PMN) function to kill invading microorganisms, but their exaggerated inflammatory responses may cause tissue injury to the host. The purpose of this study was to compare the ability of different immunoglobulin (Ig) isotypes to modulate PMN cytotoxic potential cocultured with respiratory epithelial cells challenged with bacteria.', 'Calu-3 cell monolayers were established on membranes (0.1-microm pore) in a two-chamber culture system. Escherichia coli (EC) incubated with either polyclonal SIgA or IgG was inoculated into the apical chamber and PMNs (10/mL) added to the basal chamber. PMN cytotoxic potential was indexed by % CD11b expression, superoxide anion (O2) production, and elastase release. Dextran flux was used to index Calu-3 monolayer permeability.', 'Addition of EC to PMN-Calu-3 cell coculture increased % CD11b expression, O2 production, and elastase release. IgG had no effect on PMN activation after EC challenge. SIgA abrogated PMN activation and the increase in Calu-3 cell monolayer permeability noted with EC or EC + IgG treatment groups.",
            "output": [
                "Does immunoglobulin a modulate inflammatory responses in an in vitro model of pneumonia?"
            ]
        },
        {
            "id": "task847-40339ccf8c3040dfa72cbf7cdb636629",
            "input": "Evaluation of a wide variety of pyridine N-oxide derivatives on their inhibitory activity against feline coronavirus (FIPV strain) and human SARS-CoV (Frankfurt strain-1) in cell culture.', 'FIPV and SARS-CoV were exposed to confluent Crandel feline kidney (CRFK) and simian kidney (Vero) cell cultures in the presence of serial concentrations of the test compounds. The anti-cytopathic activity of the pyridine N-oxide derivatives was monitored by spectrophotometric analysis.",
            "output": [
                "Are pyridine N-oxide derivatives inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture?"
            ]
        },
        {
            "id": "task847-54bfe1c723164af59d995f63e9b48cb8",
            "input": "To date, cardiac catheterization and endomyocardial biopsy have been considered the \"gold standard\" for rejection surveillance after heart transplantation. Factors such as patient size (i.e., infant transplantation), loss of vascular access after repeated catheterizations, and anesthesia requirements all present unique problems and risks related to pediatric rejection surveillance. Therefore, additional methods to monitor for rejection in a non-invasive, reliable and frequent manner have been sought. We studied the utility of echocardiographic measurement of the left ventricular myocardial performance index (LVMPI), a reproducible measure of combined systolic and diastolic performance, in pediatric heart transplant recipients as a method of identifying acute rejection.', 'Two-dimensional/Doppler echocardiographic studies (n = 36) were performed on 21 cardiac transplant patients (ages 6.2 to 21.9 years) at the time of endomyocardial biopsy. The LVMPI, the sum of the isovolumic contraction time and isovolumic relaxation time divided by aortic ejection time, was determined at each study, as well as other echocardiographic measures of systolic and diastolic function. Patients were grouped by concurrent histologic rejection grade and the results compared between groups.', 'Significant differences in LVMPI (p < 0.001) were noted between patients with no rejection (Grade 0; n = 23) and those with moderate to severe rejection (Grade 3; n = 5), as well as between those with no rejection and those with focal moderate (Grade 2; n = 8) rejection (p < 0.05). The LVMPI was 0.42 +/- 0.03 (mean +/- SEM) for the group without rejection, 0.57 +/- 0.06 for those with Grade 2 rejection and 0.73 +/- 0.05 for those with Grade 3 rejection. Although 9 of the 23 studies in the non-rejection group had LVMPI values exceeding 0.44 (upper threshold value), 12 of 13 patients in the rejection groups exceeded this threshold. LVMPI >or= 0.64 was associated with significant rejection in all cases in this study (n = 7). No significant differences were noted between groups for left ventricular ejection fraction or shortening fraction, percent septal or posterior wall thickening, left ventricular mass index or mitral valve deceleration time. In addition, for those individual patients with multiple studies, the LVMPI consistently increased with higher rejection grades and decreased after therapy.",
            "output": [
                "Does increased myocardial performance index correlate with biopsy-proven rejection in pediatric heart transplant recipients?"
            ]
        },
        {
            "id": "task847-51abd5338d144157ad7069f95874a9cc",
            "input": "Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined.', 'HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry. Samples with >90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1.', 'One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001 for both) compared to those with level 1 expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival.",
            "output": [
                "Is expression of hepatoma-derived growth factor correlated with lymph node metastasis and prognosis of gastric carcinoma?"
            ]
        },
        {
            "id": "task847-981f3dd78e7148b8a3fda59157b00ed1",
            "input": "A distal portion of 1p is frequently deleted in human neuroblastomas, and it is generally assumed that this region harbors at least one gene relevant for neuroblastoma development. A 1p36.3 commonly deleted region, bordered by D1S2731 and D1S214 has been defined. The present study surveys whether expression of genes mapping to this region is associated with tumor behavior.', 'Candidate genes localized within the deleted region were identified by sequence data analysis. Their expression was assessed in a cohort of 49 primary neuroblastomas using cDNA microarray analysis. Gene expression patterns associated with known prognostic markers and patient outcome were further evaluated by quantitative real-time reverse transcription-PCR in a cohort of 102 neuroblastomas.', 'The commonly deleted region spans 261 kb and encompasses two genes, FLJ10737 and CAMTA1. We found no evidence for an association of FLJ10737 expression with established prognostic variables or outcome. In contrast, low CAMTA1 expression characterized tumors with 1p deletion, MYCN amplification, and advanced tumor stages 3 and 4. Moreover, low CAMTA1 expression was significantly associated with poor outcome (P < 0.001). In multivariate analysis of event-free survival, the prognostic information of low CAMTA1 expression was independent of 1p status, MYCN status, tumor stage, and age of the patient at diagnosis (hazard ratio, 3.52; 95% confidence interval, 1.21-10.28; P = 0.02).",
            "output": [
                "Does reduced expression of CAMTA1 correlate with adverse outcome in neuroblastoma patients?"
            ]
        },
        {
            "id": "task847-71bea7244b24433ebe1d990efa76c5b9",
            "input": "Advanced hepatobiliary-pancreatic malignancy occasionally involves major vasculatures, such as the portal vein or the inferior vena cava, and complete removal of the tumor is required for longterm survival. We used a left renal vein graft to reconstruct resected vessels in some patients. In this study, we evaluated early and late renal complications of this procedure.', 'We identified 14 patients undergoing vascular reconstruction with use of a left renal vein graft in hepatobiliary-pancreatic surgery. Renal function and graft patency were assessed by observing serum creatinine levels and radiologic findings during perioperative and followup periods.', 'Of these 14 patients, 7 were men and 7 were women. Diseases included hilar cholangiocarcinoma in two, gallbladder carcinoma in two, intrahepatic cholangiocarcinoma in one, pancreas carcinoma in five, hepatic metastasis in three, and mass-forming pancreatitis in one. No significant postoperative renal dysfunction was recognized, and the mean value of the maximal serum creatinine was 1.0 mg/dL during the perioperative period. Renal scintigraphy was performed in six patients postoperatively, and there was no significant left renal dysfunction. Mean followup time was 18 months after operation, and no severe renal dysfunction was found. Graft patency, which was assessed with enhanced abdominal CT, was well maintained after operation.",
            "output": [
                "Is renal function well maintained after use of left renal vein graft for vascular reconstruction in hepatobiliary-pancreatic surgery?"
            ]
        },
        {
            "id": "task847-b84a180f245249e994b723b76fd69741",
            "input": "Proliferation of fibroblasts (desmoplastic reaction) in the lung adenocarcinomas is an important phenomenon that correlates with metastases and poor prognosis. Because basement membranes are often involved in the desmoplastic areas and many cytokines have binding capacity to basement membrane molecules, we hypothesized that basement membrane modify the paracrine effects between cancer cells and fibroblasts via the fibrogenic cytokines and this hypothesis was experimentally investigated.', 'The effects of conditioned media derived from ten lung carcinoma cell lines and normal airway epithelial cells on DNA synthesis of fetal lung fibroblasts were determined. We focused on fibroblast growth factor 2 (FGF-2) as the candidate paracrine cytokines and examined their diffusion through an experimental basement membrane matrix model, Matrigel.', 'All the conditioned media promoted DNA synthesis of fetal lung fibroblasts. Detection by ELISA methods and the neutralizing antibodies suggested that FGF-2 was one of the responsible factors for the growth promotion. Diffusion of FGF-2 across the polycarbonate membrane was suppressed by coating with Matrigel. When FGF-2-secreting A549 cells were covered with Matrigel, FGF-2 was stored in Matrigel and its diffusion into the culture media was significantly reduced. Binding of FGF-2 to Matrigel was completely blocked by a basic protein, protamine sulfate. In the presence of protamine sulfate in Matrigel overlaid on A549 cells, diffusion of FGF-2 increased 7-fold as much as that without overlaid Matrigel.",
            "output": [
                "Does basement membrane matrix modify cytokine interactions between lung cancer cells and fibroblasts?"
            ]
        },
        {
            "id": "task847-2329251afc7e477eb4d9baa0a42a368f",
            "input": "Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological behavior through its correlation with the well-known clinicopathological parameters and the expression of p53, c-erbB-2, topoisomerase IIalpha (topoIIalpha) and peroxisome proliferator-activated receptor (PPARgamma) proteins, as well as its effect on patients' survival.\", 'We performed immunohistochemistry to detect COX-2, estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2, topoIIalpha and PPARgamma proteins in 175 cases of invasive breast carcinomas. The results were elaborated by statistic analysis.', 'Cytoplasmic expression of COX-2 was detected in 66.9% of breast carcinoma samples and was inversely correlated with both nuclear and histological grade (p < 0.0001 and p = 0.039, respectively), whereas its association with PR was found to be positive (p = 0.016). COX-2 expression was inversely correlated with topoIIalpha and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPARgamma was parallel (p < 0.0001). In addition, c-erbB-2 of tumor cells was inversely correlated with COX-2 in stromal cells of the tumor (p = 0.011). Neither univariate nor multivariate analysis demonstrated any association between COX-2 expression and patient overall or disease-free survival.",
            "output": [
                "Is overexpression of cyclooxygenase-2 associated with a favorable prognostic phenotype in breast carcinoma?"
            ]
        },
        {
            "id": "task847-9d86321d997747a7ac40fe6a93ef577a",
            "input": "A prevailing paradigm is that electrical fields can promote cell migration and tissue healing. To further validate this paradigm, we tested the hypothesis that periodic direct current (DC) can enhance wound closure using an in vitro dynamic model of cell migration.', 'Layers of primary fibroblasts were wounded and treated with DC under various voltages. Repair area, cell velocity, and directionality as well as lamellipodium area were evaluated at different times. Direct current had no beneficial effect on cell migration. Moreover, prolonged stimulation under the highest voltage led to significant reduction in wound closure and cell velocity. The reduction of membrane protusions in stimulated cells may be associated with the deleterious effect of DC.",
            "output": [
                "Does periodic direct current promote wound closure in an in vitro dynamic model of cell migration?"
            ]
        },
        {
            "id": "task847-b970ae516741440e92a8f1056b033605",
            "input": "Cytotoxic immune elimination of transduced hepatocytes may limit gene therapy for inherited liver diseases. Using beta-galactosidase as a marker gene, we studied whether creation of mixed beta-galactosidase molecular hematopoietic chimerism could induce tolerance to beta-galactosidase-transduced hepatocytes.', 'Molecular hematopoietic chimerism was established in irradiated recipient mice by transplantation of either a mixture of wild-type and beta-galactosidase-transgenic bone marrow or autologous bone marrow stem cells that were transduced with beta-galactosidase lentiviral vectors. After transplantation, mice were hepatectomized and injected with beta-galactosidase recombinant retroviruses to transduce regenerating hepatocytes. We monitored the presence of beta-galactosidase-expressing hepatocytes as well as the appearance of anti-beta-galactosidase antibodies during the time.', 'In control animals, anti-beta-galactosidase antibodies and cytotoxic T-lymphocyte (CTL) response developed as early as 3 weeks after gene transfer. Transduced hepatocytes disappeared concomitantly. In bone marrow transplanted mice, tolerance could be observed in a significant proportion of animals. Tolerance resulted in permanent liver transgene expression and was absent unless a chimerism above 1% was achieved, demonstrating a threshold effect.",
            "output": [
                "Does mixed hematopoietic molecular chimerism result in permanent transgene expression from retrovirally transduced hepatocytes in mice?"
            ]
        },
        {
            "id": "task847-40b4a98ffadf4e4cab065ae55c20508b",
            "input": "In short-gut rats, we showed marked abnormalities in plasma lipid fatty acids using parenteral nutrition (PN) with lipid vs sham surgery rats. This suggests that either sensing or metabolism of parenteral lipid is abnormal in malabsorption. The goal of this study was to determine fatty acid profiles in skeletal muscle and liver in short-gut rats treated with PN compared with sham rats.', 'Sprague-Dawley rats underwent laparotomy and massive small bowel resection (or sham surgery). Rats (n = 32, 16 sham, 16 short gut) were randomly assigned to PN with lipid or fat-free PN. After 5 days, weight loss was similar in all groups, and mixed hindlimb skeletal muscle and liver were biopsied.', 'We found marked differences between liver and skeletal muscle. In livers of short-gut animals, 22:4omega6, 22:5omega6, and 22:6omega3 were higher (all p < .05) than in sham. In skeletal muscle, short gut had no effect on fatty acid profiles. In liver, fat-free PN led to significant increases in 20:3omega6, 22:4omega6, 22:5omega6, 20:3omega9, 20:5omega3, 22:6omega3, and triene/tetraene ratio (all p < .05) compared with feeding PN with lipid, irrespective of short gut. In muscle, levels of the distal long-chain fatty acid metabolites and triene/tetraene ratio were minimally affected by nutrition. Serum glucose and insulin concentrations were similar in all 4 groups.",
            "output": [
                "Do liver and skeletal muscle lipids have differing fatty acid profiles in short-gut rats fed via parenteral nutrition?"
            ]
        },
        {
            "id": "task847-8532ade4ee894e65bc740040e30e4453",
            "input": "We previously showed that the level of enteral nutrient intake determines the rate of intestinal growth in piglets. Our objective was to determine whether providing enteral nutrition in the form of elemental nutrients (glucose, amino acids, lipid [ED]) rather than cow's milk formula (lactose, protein, lipid [FORM]) reduces small intestinal growth and lactase activity.\", 'Three-week-old piglets were fed either ED (n = 7) intragastrically or FORM (n = 6) orally for 6 days.', 'Intestinal protein and DNA masses, villus height, and crypt depth were not different in ED and FORM pigs. Crypt cell proliferation, measured by in vivo bromodeoxyuridine labeling, was significantly (p < .05) higher (+37%) in ED than in FORM pigs. Rates of mucosal protein synthesis (%/d), measured by in vivo 2H-leucine incorporation, were higher (p < .05) in ED than FORM (147 vs 89) pigs. Circulating concentrations (pmol/L) of the intestinotrophic peptide, glucagon-like peptide-2 (GLP-2), were also higher (p < .05) in ED than in FORM (148 vs 87) pigs. The mean lactase-specific activity (micromol/min/g) in proximal and distal segments was higher (p < .05) in FORM than in ED (124 vs 58) pigs.",
            "output": [
                "Does feeding an elemental diet vs a milk-based formula decrease intestinal mucosal growth in infant pigs?"
            ]
        },
        {
            "id": "task847-a8f114aaa5024a1ab968b6026e384369",
            "input": "Activation of Kupffer cells by gut-derived endotoxin plays a pivotal role in alcoholic liver injury. On the other hand, it was reported that acute ethanol administration reduced activation of Kupffer cells. We found that Kupffer cells isolated from rat treated only once with ethanol were sensitized to endotoxin 24 hrs later correlatively with CD14 expression. Moreover, it was shown that Kupffer cell activation by endotoxin via Toll-like receptor (TLR)-4 is involved in alcohol-induced liver injury and ethanol-induced oxidative stress is important in the regulation of transcription factor NFkappaB activation and cytokine production by Kupffer cells. Here, we show that IRAK, one of signaling molecules of TLR-4, regulates tolerance and sensitization to LPS and acute ethanol increases in IRAK expression through a mechanism dependent upon oxidant production.', 'Female C57BL/6 mice were given ethanol (5 g/kg) intragastrically, and LPS was injected 1 or 21 hrs later. Serum transaminase levels were measured. Moreover, some mice were treated with NADPH oxidase inhibitor diphenyleneiodonium sulfate (DPI, 1 mg/kg/day) or infected with adenovirus (1 x 10 plaque-forming units, intravenously) containing IkappaB superrepressor gene, which prevent NFkappaB activation of Kupffer cells, for three days. Kupffer cells were isolated from mice 1 hr and 21 hrs after ethanol treatment. After the addition of LPS, TNF-alpha in the media was measured using ELISA, Electrophoretic mobility shift assay (EMSA) was performed to analyze DNA binding activity of NFkappaB. Further, expression of Interleukin-1 receptor-associated kinase (IRAK) was evaluated by Western blotting.', 'LPS-induced increases in transaminases were blunted in mice treated with ethanol before 1 hr. However, ethanol treatment 21 hrs earlier augmented LPS-increased transaminases three-fold over controls. Pretreatment with nonabsorbable antibiotics blocked these effects of ethanol. LPS-induced TNF-alpha production by Kupffer cells isolated from mice 1 hr after ethanol was reduced to about 60% of values from control Kupffer cells, while LPS-induced TNF-alpha production by Kupffer cells isolated from mice treated with ethanol 21 hrs earlier increased 1.5-fold over control Kupffer cells. In Kupffer cells from mice 1 hr after ethanol treatment, expression of IRAK was decreased, and LPS-induced activation of NFkappaB was decreased correlatively. In contrast, ethanol treatment to mice increased expression of IRAK in Kupffer cells 21hrs later and LPS-induced activation of NFkappaB was elevated significantly. On the other hands, DPI treatment for three days prior to ethanol did not prevent decreases in IRAK expression due to ethanol treatment for 1 hr. However, DPI treatment blunted ethanol-induced increases in IRAK expression. Additionally, inhibition of NKkappaB activation with dominant-negative IkappaBalpha blunted ethanol-induced increase in IRAK expression. Contrary, inhibition of NKkappaB did not affect decrease of IRAK expression due to ethanol treatment for 1 hr.",
            "output": [
                "Is ethanol-induced sensitization to endotoxin in Kupffer cells dependent upon oxidative stress?"
            ]
        },
        {
            "id": "task847-7fc1e709fa4e47e18067878e9b97b5d0",
            "input": "To determine the relationship between abnormalities in blood coagulation and prevalent or incident cardiovascular complications in Type 2 diabetes.', 'Prospective cohort study of 128 patients with Type 2 diabetes in whom blood samples were collected at baseline and after 1 year of follow-up. All cardiovascular complications at baseline and follow-up were recorded. Forty-three healthy, age-matched subjects served as a control group.', \"Logistic analysis revealed an independent relationship between soluble tissue factor (TF) and microvascular disease [per pg mL(-1) TF: Exp(B) = 1.008; CI(95%)1.002-1.014], or neurogenic disease [Exp(B) = 1.006; CI(95%)1.001-1.011]. The highest levels of soluble TF were observed in patients with microvascular and neurogenic disease (P < 0.001). Patients with Type 2 diabetes having a soluble TF concentration >300 pg mL(-1) are at a 15-fold higher risk for the presence of microvascular disease and at a 10-fold higher risk for the presence of neurogenic disease compared with the patients with concentrations below 100 pg mL(-1). Soluble TF was correlated with tissue type plasminogen activator, von Willebrand factor antigen, systolic blood pressure and age. Levels of F1' + 2, D-dimer, FVIII activity, t-PA and vWFag were not different among patients with micro-, macro- or neurogenic complications compared with patients without those complications. Forty-eight new micro-, macro- and/or neurogenic complications were diagnosed after 1 year follow-up. With the exception of higher F1 + 2 levels after 1 year all other markers remained unchanged. A trend toward higher soluble TF levels was observed in patients with new microvascular events (P = 0.056).",
            "output": [
                "Is soluble tissue factor a candidate marker for progression of microvascular disease in patients with Type 2 diabetes?"
            ]
        },
        {
            "id": "task847-2b9c314878204f6aba52bc962d464689",
            "input": "Maternal infections may induce placental, amniotic and, potentially, fetal inflammatory responses. As cytokine responses may be mediated by oxidative stress, we determined whether the antioxidant N-acetyl-cysteine (NAC), can attenuate maternally induced amniotic and placental cytokine responses to maternal infection (modeled by lipopolysaccharide [LPS]).', 'Gestation day 18 pregnant rats were (1) treated with LPS (100 microg/kg, body weight; intraperitoneally) alone; (2) pretreated with NAC (300 mg/kg body weight; intraperitoneally) 30 minutes before LPS; (3) posttreated with NAC 120 minutes after LPS; or (4) treated with NAC 30 minutes before and 120 minutes after LPS. Six hours after LPS administration, maternal serum and amniotic fluid interleukin-6 (IL-6) and IL-10 levels, and placental IL-6 messenger RNA levels were determined.', 'LPS increased maternal serum IL-6 (50 +/- 25 to 3444 +/- 584 pg/mL) and IL-10 (40 +/- 20 to 958 +/- 339 pg/mL) and amniotic fluid IL-6 (59 +/- 25 to 891 +/- 128 pg/mL). Pretreatment and/or posttreatment with NAC attenuated IL-6 in the maternal serum and amniotic fluid and IL-10 in the amniotic fluid. LPS also induced placental IL-6 messenger RNA that was inhibited by treatment with NAC before and after LPS.",
            "output": [
                "Does n-acetyl-cysteine suppress amniotic fluid and placenta inflammatory cytokine responses to lipopolysaccharide in rats?"
            ]
        },
        {
            "id": "task847-b6f10d5f51064468b41731e1ec99092d",
            "input": "The first Heschl's gyrus (HG) is believed to receive the core projection of the acoustic radiation. We examined if it were possible to differentiate the subcortical white matter of the HG from the superior temporal gyrus (STG) using diffusion tensor (DT) imaging.\", 'The study was approved and informed consent was obtained in accordance with the guidelines of our Institutional Review Board for human subject studies. We examined six healthy adult volunteers with DT images using 20 orientations and repeated 11 times. The fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were calculated.', 'The mean FA of the subcortical white matter of the HG (0.37) was higher than that of the STG (0.27) on both sides (P < .01). There was no statistically significant difference when comparing left and right HG and STG (P > .05). There was no statistically significant difference in mean ADC of the HGs and STGs (0.75 x 10(-3) mm(2)/sec, P > .05).",
            "output": [
                "Is fractional anisotropy higher in Heschl 's gyrus than in superior temporal gyrus in normal subjects?"
            ]
        },
        {
            "id": "task847-a254af0c7a764ba69b1477a260e30b24",
            "input": "To determine whether activin A concentrations are altered in chronic fetal hypoxemia and intrauterine fetal growth restriction (IUGR).', 'In vivo animal experimental model.', 'Department of Physiology, Monash University.', 'Chronically catherised fetal sheep in late pregnancy.', 'Chronic fetal hypoxia and IUGR were experimentally induced by single umbilical artery ligation (SUAL) in catheterised fetal sheep. Maternal and fetal blood samples and amniotic fluid (AF) samples were collected during surgery and thereafter on alternate days, until the time of delivery for analyte measurement. Fetal blood gas parameters were measured daily.', 'Plasma and AF was used to analyse activin A, prostaglandin E2 (PGE2) and cortisol and fetal blood gas analysis was undertaken in whole blood.', 'SUAL produced asymmetric IUGR and non-acidaemic chronic fetal hypoxia and resulted in preterm labour (129 [3] days). AF activin A concentrations were 10-fold higher in the SUAL group than in controls whereas levels in the fetal and maternal circulations were similar between groups.",
            "output": [
                "Does chronic fetal hypoxia increase activin A concentrations in the late-pregnant sheep?"
            ]
        },
        {
            "id": "task847-bf9f277546544af78e46714c14d07ec0",
            "input": "Non-alcoholic fatty liver disease (NAFLD) and viral hepatitis are associated with hepatic oxidative stress, which is partially dependent on the amount of hepatic fat.', 'To determine whether the circulating lipid and oxidative stress parameters could be non-invasive markers of hepatic steatosis.', 'Sixty-four patients with NAFLD or viral hepatitis were tested for lipid peroxidation products and antioxidant defence systems, lipid parameters and liver function tests.', 'Hepatic steatosis was correlated with lipids, gamma-glutamyltranspeptidase, thiobarbituric acid-reactive substances, superoxide dismutase and superoxide dismutase/erythrocyte glutathione peroxidase ratio. gamma-Glutamyltranspeptidase, triglycerides and low-density lipoprotein cholesterol were significantly higher in the presence of steatosis. No difference in blood oxidative stress markers was observed according to the presence or absence of steatosis except for the superoxide dismutase/erythrocyte glutathione peroxidase ratio. Total cholesterol, triglycerides and low-density lipoprotein cholesterol were significantly higher in the NAFLD group (n = 17, 60% mean steatosis grade) than in the viral hepatitis group (n = 20, 13% mean steatosis grade). Only superoxide dismutase was lower and vitamin E higher in NAFLD than in viral hepatitis patients.",
            "output": [
                "Are blood oxidative stress markers unreliable markers of hepatic steatosis?"
            ]
        },
        {
            "id": "task847-445a005ae84c4107b4e6fe070cff1a88",
            "input": "To examine the effect of a single spinal manipulation therapy (SMT) on the in vitro production of inflammatory cytokines, tumor necrosis factor alpha, and interleukin (IL) 1beta, in relation to the systemic (in vivo) levels of neurotransmitter substance P (SP).', 'Sixty-four asymptomatic subjects were assigned to SMT, sham manipulation, or venipuncture control group. SMT subjects received a single adjustment in the thoracic spine. Blood and serum samples were obtained from subjects before and then at 20 minutes and 2 hours after intervention. Whole-blood cultures were activated with lipopolysaccharide (LPS) for 24 hours. Cytokine production in culture supernatants and serum SP levels were assessed by specific immunoassays.', 'Over the study period, a significant proportion (P </= .05) of sham and control subjects demonstrated progressive increases in the synthesis of tumor necrosis factor alpha and IL-1beta. Conversely, in a comparable proportion of cultures from SMT-derived subjects, the production of both cytokines decreased gradually. Normalization of the observed alterations to reflect the changes relative to self-baselines demonstrated that, within 2 hours after intervention, the production of both cytokines increased significantly (P < .001 to .05) in both controls. In contrast, a significant (P < .001 to .05) reduction of proinflammatory cytokine secretion was observed in cultures from SMT-receiving subjects. In all study groups, serum levels of SP remained unaltered within 2 hours after intervention.",
            "output": [
                "Does spinal manipulative therapy reduce inflammatory cytokines but not substance P production in normal subjects?"
            ]
        },
        {
            "id": "task847-9fd15b52a2bf418ba9f998a5c254f1dd",
            "input": "Colonic response to single-dose irradiation is characterized by epithelial denudation followed by restitution. Extracellular matrix (ECM) remodeling is involved in both of these phases. The aim of this study was to characterize the contribution of matrix metalloproteinases (MMPs) and of their stimulatory and inhibitory pathways in radiation-induced ecm remodeling in colonic tissue.', 'Rats were irradiated with single-dose 10 Gy X-rays to the abdomen. Activity, localization, and mRNA levels of MMPs and molecules involved in their activation and inhibition (plasmin/plasminogen; TIMPs), of inflammatory mediators (IL-1beta, TNF-alpha) in the distal colon, 1, 3, and 7 days after irradiation were analyzed using a combination of approaches including zymography, immunohistochemistry, and real-time reverse transcriptase-polymerase chain reaction (RT-PCR).', 'The main finding of this study is that radiation-induced alteration of the mucosal structure is concomitant with local increased expression and activation of MMP subtypes involved in basement membrane degradation (MMP-2, -3, and -9). We investigated MMP-2 activation pathways and found an early increase in mRNA levels of soluble inflammatory mediators (TNF-alpha and IL-1beta). Furthermore, transcription and activity of MMP-2 activating molecules, such as MMP-14, and molecules involved in the plasminogen/plasmin system were found to increase during the denudation phase. Interestingly, induction of MMP inhibitors TIMP-1 and PAI-1 was observed during the restitution phase. MMP inhibitors may be able to stop acute wound healing response by inhibiting ECM degradation.",
            "output": [
                "Are expression and activation of MMP -2 , -3 , -9 , -14 induced in rat colon after abdominal X-irradiation?"
            ]
        },
        {
            "id": "task847-28e89a78a00441e287560901d1907e2e",
            "input": "Medical documentation is important for communication among health care professionals, research, legal defense, and reimbursement. Previous studies have indicated insufficient documentation by health care providers and resistance among physicians to comply with the new guidelines. Data in the intensive care unit (ICU) subpopulation are scarce. We examined the hypothesis that a newly appointed neurointensivist may alter documentation practices in a university hospital setting.', 'We sampled medical records of neurological intensive care unit (NICU) patients admitted with three specific diagnoses (head trauma, intracerebral hemorrhage, and subarachnoid hemorrhage) and examined changes in the documentation of important prognostic variables in two time periods: before and after the appointment of a neurointensivist.', \"Overall, documentation improved from 32.5 to 57.5% (odds ratio, 95% confidence interval 2.8, 1.9-4.2) in the after period. Documentation using Glasgow Coma Scale, clot volume, Hunt & Hess scale, and Fisher's grade also improved significantly in each of the diagnoses examined in the after period.",
            "output": [
                "Does documentation in medical records improve after a neurointensivist 's appointment?"
            ]
        },
        {
            "id": "task847-8274d2649a7d47bf84005df2c0f27eca",
            "input": "Several lines of evidence suggest that the dietary isoflavone genistein (Gen) has beneficial effects with regard to cardiovascular disease and in particular on aspects related to blood pressure and angiogenesis. The biological action of Gen may be, at least in part, attributed to its ability to affect cell signalling and response. However, so far, most of the molecular mechanisms underlying the activity of Gen in the endothelium are unknown.', 'To examine the transcriptional response to 2.5 microM Gen on primary human endothelial cells (HUVEC), we applied cDNA array technology both under baseline condition and after treatment with the pro-atherogenic stimulus, copper-oxidized LDL. The alteration of the expression patterns of individual transcripts was substantiated using either RT-PCR or Northern blotting. Gen significantly affected the expression of genes encoding for proteins centrally involved in the vascular tone such as endothelin-converting enzyme-1, endothelin-2, estrogen related receptor alpha and atrial natriuretic peptide receptor A precursor. Furthermore, Gen countered the effect of oxLDL on mRNA levels encoding for vascular endothelial growth factor receptor 165, types 1 and 2.",
            "output": [
                "Does genistein affect the expression of genes involved in blood pressure regulation and angiogenesis in primary human endothelial cells?"
            ]
        },
        {
            "id": "task847-d551f3bd0fa547ecae5530ab11c073e4",
            "input": "Isovolumic acceleration (IVA) obtained by tissue Doppler echocardiography (TDE) is a sensitive and relatively load-independent index for assessing systolic ventricular function. IVA also has the ability to describe the force-frequency relationship during incremental atrial pacing in vivo.', 'We sought to assess the ability of IVA to detect global left ventricular (LV) dysfunction induced by coronary constriction.', 'In 6 open-chest anesthetized pigs we examined right ventricular and LV long-axis function by TDE (4-chamber view) with simultaneous invasive measurements of intraventricular pressure, maximum dP/dt, minimum dP/dt, and tau by microtip catheter. A pneumatic cuff was placed around the proximal portion of left anterior descending coronary artery (LAD) and distal flow was monitored by transonic flow probe. Mean arterial pressures were monitored by indwelling cannula. Baseline studies assessed force-frequency relationships with TDE and invasive measurements during incremental pacing from 100 to 200/min (20/min increments every 10 minutes). The protocol was repeated 10 minutes after balloon inflation to reduce LAD blood flow by 50%.', 'Compared with baseline, LV pressure decreased significantly (P = .03, 2-way analysis of variance) as did maximum dP/dt (P < .004) with LAD constriction. At the same time IVA and isovolumic velocity at the LV free wall were significantly reduced (P < .002 and P = .04, respectively) and both IVA and isovolumic velocity were correlated with dP/dt (r = 0.45, P < .002, and r = 0.35, P < .02, respectively). TDE systolic indices were unchanged in the right ventricle.",
            "output": [
                "Do isovolumic but not ejection phase Doppler tissue indices detect left ventricular dysfunction caused by coronary stenosis?"
            ]
        },
        {
            "id": "task847-a020fd7e25b448b3bcd57fa7365ce467",
            "input": "miR-155 is an oncogenic miRNA that is often overexpressed in cancer and is associated with poor prognosis. miR-155 can target several DNA repair factors, including RAD51, MLH1, and MSH6, and its overexpression results in an increased mutation frequency in vitro, although the mechanism has yet to be fully understood. Here, we demonstrate that overexpression of miR-155 drives an increased mutation frequency both in vitro and in vivo, promoting genomic instability by affecting multiple DNA repair pathways. miR-155 overexpression causes a decrease in homologous recombination, but yields a concurrent increase in the error-prone nonhomologous end-joining pathway. Despite repressing established targets MLH1 and MSH6, the identified mutation pattern upon miR-155 overexpression does not resemble that of a mismatch repair-deficient background. Further investigation revealed that all four subunits of polymerase delta, a high-fidelity DNA replication, and repair polymerase are downregulated at the mRNA level in the context of miR-155 overexpression. FOXO3a, a transcription factor and known target of miR-155, has one or more putative binding site(s) in the promoter of all four polymerase delta subunits. Finally, suppression of FOXO3a by miR-155 or by siRNA knockdown is sufficient to repress the expression of the catalytic subunit of polymerase delta, POLD1, at the protein level, indicating that FOXO3a contributes to the regulation of polymerase delta levels.",
            "output": [
                "Does miR-155 Overexpression promote Genomic Instability by Reducing High-fidelity Polymerase Delta Expression and Activating Error-Prone DSB Repair?"
            ]
        },
        {
            "id": "task847-3ac15831058f445e95067e9f091cf839",
            "input": "The aim of the study was to analyze John Cunningham virus (JCV) serology in natalizumab-treated patients over time and assess whether they are influenced by natalizumab treatment.', 'German (n = 1,921; 525 longitudinally) and French (n = 1,259; 711 longitudinally) patients were assessed for JCV serology alongside their therapy with natalizumab.', 'JCV serostatus changed in 69 of 525 longitudinally followed German patients (13.1%) over 14.8 months. Seroconversion according to serostatus was seen in 43 of 339 initially JCV- German patients (12.7% in 14.8 months; 10.3% per year) and 41 of 243 initially JCV- French patients (16.9% in 24 months; 8.5% per year). JCV index values could be reproduced (R (2) = 0.89) with the caveat of 8 of 50 samples (16%) being set into different risk categories between 2 assessments. Index values of JCV+ patients rose over time (p = 0.009) but not because of aging. Treatment with natalizumab was associated with a 15.9% increase of value in JCV+ patients in 14.8 months (12.9% per year).",
            "output": [
                "Is therapy with natalizumab associated with high JCV seroconversion and rising JCV index values?"
            ]
        },
        {
            "id": "task847-b278d2dc8ff54017bcc9017974719d8f",
            "input": "The purpose of this study was to assess the potential immunosuppressive role of daclizumab, a humanized monoclonal antibody against the \u03b1 chain of the interleukin 2 receptor, in vivo, by comparing immune responses to the 2013 seasonal influenza vaccination between patients with multiple sclerosis (MS) on long-term daclizumab therapy and controls.', 'Previously defined subpopulations of adaptive immune cells known to correlate with the immune response to the influenza vaccination were evaluated by 12-color flow cytometry in 23 daclizumab-treated patients with MS and 14 MS or healthy controls before (D0) and 1 day (D1) and 7 days (D7) after administration of the 2013 Afluria vaccine. Neutralizing antibody titers and CD4(+), CD8(+) T cell, B cell, and natural killer cell proliferation to 3 strains of virus contained in the Afluria vaccine were assessed at D0, D7, and 180 days postvaccination.', 'Daclizumab-treated patients and controls demonstrated comparable, statistically significant expansions of previously defined subpopulations of activated CD8(+) T cells and B cells that characterize the development of effective immune responses to the influenza vaccine, while proliferation of T cells to influenza and control antigens was diminished in the daclizumab cohort. All participants fulfilled FDA criteria for seroconversion or seroprotection in antibody assays.",
            "output": [
                "Do patients with MS under daclizumab therapy mount normal immune responses to influenza vaccination?"
            ]
        },
        {
            "id": "task847-0094a86947744c149812459c41bae0ba",
            "input": "Disease heterogeneity in patients with severe asthma and its relationship to inflammatory mechanisms remain poorly understood.', 'We aimed to identify and replicate clinicopathologic endotypes based on analysis of blood and sputum parameters in asthmatic patients.', 'One hundred ninety-four asthmatic patients and 21 control subjects recruited from 2 separate centers underwent detailed clinical assessment, sputum induction, and phlebotomy. One hundred three clinical, physiologic, and inflammatory parameters were analyzed by using topological data analysis and Bayesian network analysis.', 'Severe asthma was associated with anxiety and depression, obesity, sinonasal symptoms, decreased quality of life, and inflammatory changes, including increased sputum chitinase 3-like protein 1 (YKL-40) and matrix metalloproteinase (MMP) 1, 3, 8, and 12 levels. Topological data analysis identified 6 clinicopathobiologic clusters replicated in both geographic cohorts: young, mild paucigranulocytic; older, sinonasal disease; obese, high MMP levels; steroid resistant TH2 mediated, eosinophilic; mixed granulocytic with severe obstruction; and neutrophilic, low periostin levels, severe obstruction. Sputum IL-5 levels were increased in patients with severe particularly eosinophilic forms, whereas IL-13 was suppressed and IL-17 levels did not differ between clusters. Bayesian network analysis separated clinical features from intricately connected inflammatory pathways. YKL-40 levels strongly correlated with neutrophilic asthma and levels of myeloperoxidase, IL-8, IL-6, and IL-6 soluble receptor. MMP1, MMP3, MMP8, and MMP12 levels were associated with severe asthma and were correlated positively with sputum IL-5 levels but negatively with IL-13 levels.",
            "output": [
                "Does multidimensional endotyping in patients with severe asthma reveal inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1?"
            ]
        },
        {
            "id": "task847-5f1db011c4c14f6bb8e9b3500db54295",
            "input": "Stem cells have multiple ways of differentiating and restoring healing. This feature may recommend their usage for decreasing the incidence of anastomotic fistulas in the colon in case of colorectal malignancy.', 'To determine whether stem cells are improving digestive healing, we performed a literature review using as Mesh terms: \"anastomotic leak\", \"stem cells\", and \"colonic anastomoses\", followed by an observational analysis on 3 experimental studies.', 'We found that stem cells increase bursting pressure by an elevated rate of angiogenesis. In addition, the hydroxyproline content of the anastomoses is significantly increased in the stem cell group. The results concerning microscopic characteristics of digestive healing varied markedly between studies.",
            "output": [
                "Do stem cells improve the quality of colonic anastomoses - A systematic review?"
            ]
        },
        {
            "id": "task847-8bb2f7b83ba3460c924b94e183508baa",
            "input": "Oxidative stress has been reported to be a main cause of neuronal cell death in ischemia reperfusion injury (IRI). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important factor involved in anti-oxidative responses. We previously reported that bardoxolone methyl (BARD), an Nrf2 activator, prevented damage induced by IRI. In this study, we investigated the effect of BARD on hemorrhagic transformation in the context of blood brain barrier (BBB) protection.', 'Mice received pre-treatment with warfarin (4.0 mg/kg, p.o.). IRI was subsequently induced 18 h after the warfarin administration by transient middle cerebral artery occlusion (MCAO) for 6 h. BARD (0.06, 0.2, 0.6 or 2.0 mg/kg) or saline was injected intravenously immediately after reperfusion. The infarct volume, neurological score, intracranial hemorrhage volume, and BBB permeability were evaluated 24 h after MCAO. The survival rate and behavioral functional recovery were evaluated for 7 days following IRI. Furthermore, the effects of BARD on BBB components were investigated by western blotting and immunostaining analysis.', 'BARD suppressed warfarin-mediated increases in the intracranial hemorrhage volume without affecting the infarct volume. BBB permeability was also suppressed by administration of BARD. Western blotting showed that BARD increased expression of BBB components such as endothelial cells, pericytes, and tight junction proteins. Furthermore, immunostaining showed that BARD induced localization of Nrf2 to endothelial cells and pericytes.",
            "output": [
                "Does nrf2 activator ameliorate hemorrhagic transformation in focal cerebral ischemia under warfarin anticoagulation?"
            ]
        },
        {
            "id": "task847-8fffec7668b54d6b831705d58981881a",
            "input": "Growth factors induce a characteristically short-lived Ras activation in cells emerging from quiescence. Extensive work has shown that transient as opposed to sustained Ras activation is critical for the induction of mitogenic programs. Mitogen-induced accumulation of active Ras-GTP results from increased nucleotide exchange driven by the nucleotide exchange factor Sos. In contrast, the mechanism accounting for signal termination and prompt restoration of basal Ras-GTP levels is unclear, but has been inferred to involve feedback inhibition of Sos. Remarkably, how GTP-hydrolase activating proteins (GAPs) participate in controlling the rise and fall of Ras-GTP levels is unknown.', 'Monitoring nucleotide exchange of Ras in permeabilized cells we find, unexpectedly, that the decline of growth factor-induced Ras-GTP levels proceeds in the presence of unabated high nucleotide exchange, pointing to GAP activation as a major mechanism of signal termination. Experiments with non-hydrolysable GTP analogues and mathematical modeling confirmed and rationalized the presence of high GAP activity as Ras-GTP levels decline in a background of high nucleotide exchange. Using pharmacological and genetic approaches we document a raised activity of the neurofibromatosis type I tumor suppressor Ras-GAP neurofibromin and an involvement of Rsk1 and Rsk2 in the down-regulation of Ras-GTP levels.",
            "output": [
                "Does feedback activation of neurofibromin terminate growth factor-induced Ras activation?"
            ]
        },
        {
            "id": "task847-2814f60d30584eabb6a434b4e4557898",
            "input": "Sensory processing deficits are common in autism spectrum disorders, but the underlying mechanisms are unclear. Fragile X Syndrome (FXS) is a leading genetic cause of intellectual disability and autism. Electrophysiological responses in humans with FXS show reduced habituation with sound repetition and this deficit may underlie auditory hypersensitivity in FXS. Our previous study in Fmr1 knockout (KO) mice revealed an unusually long state of increased sound-driven excitability in auditory cortical neurons suggesting that cortical responses to repeated sounds may exhibit abnormal habituation as in humans with FXS. Here, we tested this prediction by comparing cortical event related potentials (ERP) recorded from wildtype (WT) and Fmr1 KO mice. We report a repetition-rate dependent reduction in habituation of N1 amplitude in Fmr1 KO mice and show that matrix metalloproteinase-9 (MMP-9), one of the known FMRP targets, contributes to the reduced ERP habituation. Our studies demonstrate a significant up-regulation of MMP-9 levels in the auditory cortex of adult Fmr1 KO mice, whereas a genetic deletion of Mmp-9 reverses ERP habituation deficits in Fmr1 KO mice. Although the N1 amplitude of Mmp-9/Fmr1 DKO recordings was larger than WT and KO recordings, the habituation of ERPs in Mmp-9/Fmr1 DKO mice is similar to WT mice implicating MMP-9 as a potential target for reversing sensory processing deficits in FXS. Together these data establish ERP habituation as a translation relevant, physiological pre-clinical marker of auditory processing deficits in FXS and suggest that abnormal MMP-9 regulation is a mechanism underlying auditory hypersensitivity in FXS.",
            "output": [
                "Does matrix metalloproteinase-9 deletion rescue auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome?"
            ]
        },
        {
            "id": "task847-cf0990897020407f9d796aca5234494f",
            "input": "Infantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability.', 'Between 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged.', 'A total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9-9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5-91.7) and 94.0% (95% CI 82.5-98.0).",
            "output": [
                "Is conservative strategy in infantile fibrosarcoma possible : The European paediatric Soft tissue sarcoma Study Group experience?"
            ]
        },
        {
            "id": "task847-34088e2000314e8589db9c4cf482c36a",
            "input": "To correlate cerebral cavernous malformations (CCMs) disease aggressiveness with peripheral blood biomarkers hypothesized mechanistically.', 'A prospective case-control study enrolled 43 CCM patients, where 25-(OH) vitamin D, HDL and non-HDL cholesterol, CRP plasma levels and leukocyte ROCK activity were correlated with parameters of disease aggressiveness reflecting chronic and acute domains.', 'Patients with one or more features of chronically aggressive disease (early age at symptom onset, two or more symptomatic bleeds, high lesion burden) had significantly lower 25-(OH) vitamin D and non-HDL cholesterol levels in comparison to patients without these features.",
            "output": [
                "Do peripheral plasma vitamin D and non-HDL cholesterol reflect the severity of cerebral cavernous malformation disease?"
            ]
        },
        {
            "id": "task847-d9d41e73e81345ef89ce44e7cf81b248",
            "input": "The specific aim of the study was to investigate and compare epiphyseal length and extension in the proximal humerus, closure in the growth plate and bone marrow signal intensity related to the proximal humeral physis in the dominant arm and the non-dominant arm of the asymptomatic adolescent elite tennis player.', 'The study sample included 35 asymptomatic elite young tennis players (15 males and 20 females, mean age 17.4\\xa0years\\xa0\u00b1\\xa02.7). Each player contributed with two shoulders to the MRI measurement. The non-dominant arm was used as a control.', 'Relative reliability between the radiologists was excellent (ICC 0.78-0.96). Statistically significant differences between dominant arm and non-dominant arm in epiphyseal length (mm) laterally (DA 27.3 vs NDA 26.7) were shown. Statistically significant differences were also found in epiphyseal extension (mm) laterally (DA 36.1 vs NDA 35.1) and ventrally (DA 36.2 vs NDA 34.8). No statistically significant differences were found between dominant arm and non-dominant arm in epiphyseal extension (mm) medially (DA 31.7 vs NDA 31.7) and dorsally (DA 22.6 vs NDA 22.1).",
            "output": [
                "Do asymptomatic elite young tennis players show lateral and ventral growth plate alterations of proximal humerus on MRI?"
            ]
        },
        {
            "id": "task847-89a196af8810417fa513468fc4f33fb7",
            "input": "Portal vein thrombosis (PVT) is frequently observed in cirrhosis and may be a clinically important complication. In vitro assays for endogenous thrombin potential (ETP) demonstrated that in cirrhosis plasma has intrinsic resistance to the anticoagulant action of thrombomodulin (TM-R). This study retrospectively explores the association of TM-R with de novo PVT and its clinical impact on cirrhosis.', 'Fifty-three patients with cirrhosis were tested for ETP-ratio with/without thrombomodulin. Clinical, endoscopic variables, presence/absence of PVT by Doppler-US and/or CT examination were collected at baseline and up to 4 years from baseline. The de novo PVT was the primary clinical end-point. Portal hypertension (PHT)-related complications and transplantation free survival were secondary end-points. ETP-ratio higher than the 95\u00b0 percentile of the distribution in 173 healthy controls defined TM-R.', 'During 48 months of follow-up, 11 patients developed de novo PVT, with preference for the 36 patients with TM-R after adjusting for Child-Pugh class (HR: 8.354; 90%CI:1.475 - 47.305; P = 0.009). Seventeen patients experienced PHT-related complications, 23 either died or underwent liver transplantation. PHT complications and transplantation free survival were associated with TM-R, but were independently predicted by Child-Pugh class, only. Same results were obtained by considering the MELD score.",
            "output": [
                "Is resistance to thrombomodulin associated with de novo portal vein thrombosis and low survival in patients with cirrhosis?"
            ]
        },
        {
            "id": "task847-3f14b5d4e2544f398f715904e9fdf8f3",
            "input": "To review the publication fate of abstracts presented at dental conferences and investigate the association between full publication proportion (FPP) and abstract characteristics, conference characteristics, and methodological quality of primary studies.', 'PubMed, EMBASE, and Google Scholar were searched up to November 2014 for studies that reported at least one FPP of abstracts presented at dental conferences, with a follow-up length of no less than 48\\xa0months.', 'Sixteen studies involving 10,365 abstracts presented at 52 conferences were included. The pooled FPP was 29.62% (95% confidence interval: 22.90%, 36.81%) for all presented abstracts and 51.97% (95% confidence interval: 43.19%, 60.70%) for randomized controlled trial abstracts. Abstract characteristics significantly associated with higher FPP included reporting of statistical analysis (P\\xa0<\\xa00.001), oral presentation (P\\xa0<\\xa00.001), basic science research (P\\xa0=\\xa00.047), and reporting of financial support (P\\xa0=\\xa00.009). Abstracts with positive (P\\xa0=\\xa00.29) or statistically significant results (P\\xa0=\\xa00.33) were not published more often than negative or nonsignificant results, respectively. In multivariable meta-regression analysis, conferences held in Asia (P\\xa0<\\xa00.001) and at a continental rather than national level (P\\xa0<\\xa00.001) were significantly associated with higher FPP.",
            "output": [
                "Are thirty percent of abstracts presented at dental conferences published in full : a systematic review?"
            ]
        },
        {
            "id": "task847-cda5836cfa414b5cb7ab0816881d4313",
            "input": "Endothelin-1 levels are raised in chronic thromboembolic pulmonary hypertension. Our aim in this study was to identify the presence of endothelin receptors in patients with CTEPH by analysing tissue removed at pulmonary endarterectomy.', 'Pulmonary endarterectomy tissue cross-sections were analysed using autoradiography with [(125)I]-ET-1 using ligands selective for ETA or ETB to determine sub-type distribution. The precise cellular localisation of ETA and ETB receptors was determined using selective antisera to both sub-types and compared with haematoxylin and eosin, Elastic Van Gieson and smooth muscle actin labelled sections.', 'Two patterns of ET-1 binding were found. In sections with frequent recanalised channels, ET-1 bound to the smooth muscle cells surrounding the channels. In sections where there was less organised thrombus with no obvious re-canalisation, minimal ET-1 binding was observed. Some contractile type smooth muscle cells not associated with recanalised channels and diffusely spread throughout the PEA material were associated with ET receptor antibody binding on immunohistochemistry. There was a greater expression of the ETA receptor type in the specimens.",
            "output": [
                "Do endothelin ETA receptors predominate in chronic thromboembolic pulmonary hypertension?"
            ]
        },
        {
            "id": "task847-887d2a62c40b4f18804ab6e874b4171f",
            "input": "To determine whether tirofiban can prevent microcirculation dysfunction during delayed percutaneous coronary intervention (PCI) of spontaneously recanalized and severe narrowing coronary artery in patients with acute myocardial infarction.', '62 patients who have a single angiographically confirmed narrowing culprit coronary artery for more than 75% between 7 and 14 days after the onset of acute myocardial infarction were randomly divided into the tirofiban group (32 cases) and the placebo group (30 cases). All the patients received measurement of the index of microcirculatory resistance (IMR) before tirofiban/placebo administration and PCI. After PCI, IMR value was measured again.', 'There was no significant variation between the two groups before PCI (11.67 \u00b1 6.45 of placebo group vs. 14.65 \u00b1 12.45 of tirofiban group, P=0.158). After PCI, the IMR value of the tirofiban group is significantly lower than that of the placebo group (23.63 \u00b1 9.91 of placebo group vs. 16.75 \u00b1 9.98 of tirofiban group, P=0.008).",
            "output": [
                "Does intracoronary injection of tirofiban prevent microcirculation dysfunction during delayed percutaneous coronary intervention in patients with acute myocardial infarction?"
            ]
        },
        {
            "id": "task847-45236dd91c764f84b0feced26c3ad6b8",
            "input": "Early trauma-induced coagulopathy may increase susceptibility to nosocomial infections such as ventilator-associated pneumonia. However, the relationship between trauma- induced coagulopathy and the development of ventilator-associated pneumonia in spinal cord injury patients has not been evaluated.', 'We conducted a 5-year retrospective study of 300 spinal cord injury patients admitted to Level 1 trauma center. Standard coagulation studies were evaluated upon arrival, prior to fluid resuscitative efforts, and at 24 \\u200ah after admission. Based on these studies, three groups of patients were identified: no coagulopathy, latent coagulopathy, and admission coagulopathy. Ventilator- associated pneumonia was identified utilizing Centers for Disease Control and Prevention criteria. Since we used the data in the trauma registry and did not have the information on FiO2 and PEEP, we elected to use the VAP terminology and not the VAE sequence. Demographic, injury, and clinical characteristics were compared among no coagulopathy, latent coagulopathy, and admission coagulopathy groups using chi-square test and ANOVA for categorical and continuous variables, respectively. A logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between coagulopathy and both ventilator-associated pneumonia and mortality.', 'The incidence of ventilator-associated pneumonia was 54.5% (OR 4.01, 95% CI 1.76-9.15) in spinal cord injury patients with admission coagulopathy, compared with the 17.5% in spinal cord injury patients with no coagulopathy. Mortality was significantly higher in spinal cord injury patients with admission coagulopathy than in spinal cord injury patients with no coagulopathy (OR 6.14, 95% CI 1.73-21.73).After adjusting for age, race, injury mechanism, Injury Severity Score, base deficit at admission, the number of pRBC units transfused in the first 24\\u200a h, and hospital stay, only the association of ventilator-associated pneumonia among those with admission coagulopathy remained significant (OR 3.51, 95% CI 1.48-8.32). Compared with those with no coagulopathy, patients with admission coagulopathy had a higher odds of death (4.10, 95% CI 1.53-11.02), though this association lost significance after adjustment (OR 3.56, 95% CI 0.90-14.12). There was no statistical difference in mortality for latent coagulopathy compared with no coagulopathy patients.",
            "output": [
                "Is early Trauma-Induced Coagulopathy Associated with Increased Ventilator-Associated Pneumonia in Spinal Cord Injury Patients?"
            ]
        },
        {
            "id": "task847-976e1f8d95444476b188e675ecb365e3",
            "input": "Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such patients may benefit from completion lymph node dissection (CLND).', 'In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin [H and E] serial sections and immunohistochemistry [IHC]) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison.', 'A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p\\xa0= 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p\\xa0=\\xa00.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p\\xa0= 0.9044).",
            "output": [
                "Does molecular Staging of Sentinel Lymph Nodes identify Melanoma Patients at Increased Risk of Nodal Recurrence?"
            ]
        },
        {
            "id": "task847-e94d81967de7442ab61a4ef4a17c530f",
            "input": "Interferon (IFN)-\u03b3 is a major cytokine produced by immune cells that plays diverse roles in modulating both the immune system and bone metabolism, but its role in autogenous bone grafting remains unknown. Here, we present that local IFN-\u03b3 administration improved the efficacy of autogenous bone graft treatment in an experimental rat model.', 'An autogenous bone graft model was prepared with critically sized rat calvariae defects. Four weeks (w) after bone graft implantation, rats were treated locally with IFN-\u03b3 or were not treated. The effect of IFN-\u03b3 on bone formation was evaluated for up to 8w with micro-computed tomography, quantitative histomorphometry, and Von Kossa staining. Osteoclastogenesis was assessed by tartrate-resistant acid phosphatase staining. Immunohistochemistry staining or quantitative polymerase chain reactions were used to estimate the expression of osteoclast differentiation factor and inflammatory cytokines including tumor necrosis factor (TNF)-\u03b1, a well-known stimulant of osteoclastogenesis and an inhibitor of osteoblast activity, in defects.', 'Newly formed bone gradually replaced the autogenous bone grafts within 4w, although severe bone resorption with osteoclastogenesis and TNF-\u03b1 expression occurred after 6w in the absence of IFN-\u03b3 administration. IFN-\u03b3 administration markedly attenuated bone loss, osteoclastogenesis, and TNF-\u03b1 expression, while it enhanced bone formation at 8w.",
            "output": [
                "Does interferon-\u03b3 enhance the efficacy of autogenous bone grafts by inhibiting postoperative bone resorption in rat calvarial defects?"
            ]
        },
        {
            "id": "task847-bce3cb3b2a804b4e82030b59eecebeb8",
            "input": "Biological evidence reported in the literature supports the role of CELSR1 as being essential for valvular function in murine lymphatics. Yet thus far, there have been no variants in CELSR1 associated with lymphatic dysfunction in humans.', 'In this report, a rare early inactivating mutation in CELSR1 is found to be causal for non-syndromic, lower extremity lymphedema in a family across three generations. Near-infrared fluorescence lymphatic imaging shows that instead of being propelled within the lumen of well-defined lymphatic vessels, lymph moved in regions of both legs in an unusual fashion and within sheet-like structures.",
            "output": [
                "Is a novel mutation in CELSR1 associated with hereditary lymphedema?"
            ]
        },
        {
            "id": "task847-c50549c8ea1049ecbd87fa6e7e90185d",
            "input": "Transcription in Escherichia coli generates positive supercoiling in the DNA, which is relieved by the enzymatic activity of gyrase. Recently published experimental evidence suggests that transcription initiation and elongation are inhibited by the buildup of positive supercoiling. It has therefore been proposed that intermittent binding of gyrase plays a role in transcriptional bursting. Considering that transcription is one of the most fundamental cellular processes, it is desirable to be able to account for the buildup and release of positive supercoiling in models of transcription.', \"Here we present a detailed biophysical model of gene expression that incorporates the effects of supercoiling due to transcription. By directly linking the amount of positive supercoiling to the rate of transcription, the model predicts that highly transcribed genes' mRNA distributions should substantially deviate from Poisson distributions, with enhanced density at low mRNA copy numbers. Additionally, the model predicts a high degree of correlation between expression levels of genes inside the same supercoiling domain.",
            "output": [
                "Does a biophysical model of supercoiling dependent transcription predict a structural aspect to gene regulation?"
            ]
        },
        {
            "id": "task847-68c6123b7cda419289b05f0dc5977973",
            "input": "Mucus hypersecretion and neutrophil infiltration are important characteristics of airway inflammation. Epidermal growth factor receptor (EGFR) transactivation induces mucus and inflammatory cytokine secretion from airway epithelial cells. To elucidate the roles of EGFR in airway inflammation, the in vitro effects on mucin production and interleukin (IL) 8 secretion from cultured airway epithelial cells and the in vivo effects on mucus hypersecretion and neutrophil infiltration in rat nasal mucosa of the EGFR tyrosine kinase inhibitor AG1478 were examined.', 'The in vitro effects of AG1478 treatment of cultured NCI-H292 cells on lipopolysaccharide (LPS) induced or tumor necrosis factor (TNF) \u03b1 induced MUC5AC mucin and IL-8 secretion were evaluated. Hypertrophic and metaplastic changes of goblet cells, mucus production and neutrophil infiltration in rat nasal epithelium were induced by intranasal instillation of LPS in vivo, and the inhibitory effects of AG1478 by intraperitoneal injection or intranasal instillation were examined.', 'AG1478 (1-1000 nM) significantly inhibited both LPS-induced and TNF-\u03b1-induced secretion of MUC5AC and IL-8 from cultured NCI-H292 cells in a dose-dependent manner. The expression of MUC5AC and IL-8 messenger RNAs was also significantly inhibited. Intranasal instillation of AG1478 one hour after intranasal LPS instillation significantly inhibited LPS-induced goblet cell metaplasia, mucus production, and neutrophil infiltration in rat nasal epithelium, as did intraperitoneal injection of AG1478 one hour before LPS instillation.",
            "output": [
                "Does epidermal growth factor receptor inhibitor AG1478 inhibit mucus hypersecretion in airway epithelium?"
            ]
        },
        {
            "id": "task847-6719381de09744b99f24466a31bb359e",
            "input": "Anthrax is a rare disease in humans but elicits great public fear because of its past use as an agent of bioterrorism. Injectional anthrax has been occurring sporadically for more than ten years in heroin consumers across multiple European countries and this outbreak has been difficult to trace back to a source.', 'We took a molecular epidemiological approach in understanding this disease outbreak, including whole genome sequencing of Bacillus anthracis isolates from the anthrax victims. We also screened two large strain repositories for closely related strains to provide context to the outbreak.', 'Analyzing 60 Bacillus anthracis isolates associated with injectional anthrax cases and closely related reference strains, we identified 1071 Single Nucleotide Polymorphisms (SNPs). The synapomorphic SNPs (350) were used to reconstruct phylogenetic relationships, infer likely epidemiological sources and explore the dynamics of evolving pathogen populations. Injectional anthrax genomes separated into two tight clusters: one group was exclusively associated with the 2009-10 outbreak and located primarily in Scotland, whereas the second comprised more recent (2012-13) cases but also a single Norwegian case from 2000.",
            "output": [
                "Does whole Genome Analysis of Injectional Anthrax identify Two Disease Clusters Spanning More Than 13 Years?"
            ]
        },
        {
            "id": "task847-f2395344d0a84022969cae29395398d6",
            "input": "Tuberculous pericarditis is considered to be a paucibacillary process; the large pericardial fluid accumulation is attributed to an inflammatory response to tuberculoproteins. Mortality rates are high. We investigated the role of clinical and microbial factors predictive of tuberculous pericarditis mortality using the artificial intelligence algorithm termed classification and regression tree (CART) analysis.', 'Patients were prospectively enrolled and followed in the Investigation of the Management of Pericarditis (IMPI) registry. Clinical and laboratory data of 70 patients with confirmed tuberculous pericarditis, including time-to-positive (TTP) cultures from pericardial fluid, were extracted and analyzed for mortality outcomes using CART. TTP was translated to log10 colony forming units (CFUs) per mL, and compared to that obtained from sputum in some of our patients.', 'Seventy patients with proven tuberculous pericarditis were enrolled. The median patient age was 35 (range: 20-71) years. The median, follow up was for 11.97 (range: 0\u00b703-74.73) months. The median TTP for pericardial fluid cultures was 22 (range: 4-58) days or 3.91(range: 0\u00b75-8\u00b796) log10CFU/mL, which overlapped with the range of 3.24-7.42 log10CFU/mL encountered in sputum, a multi-bacillary disease. The overall mortality rate was 1.43 per 100 person-months. CART identified follow-up duration of 5\u00b723 months on directly observed therapy, a CD4 + count of \u2264 199.5/mL, and TTP \u2264 14 days (bacillary load \u2265 5.53 log10 CFU/mL) as predictive of mortality. TTP interacted with follow-up duration in a non-linear fashion.",
            "output": [
                "Is tuberculous Pericarditis Multibacillary and Bacterial Burden Drives High Mortality?"
            ]
        },
        {
            "id": "task847-ba6a61affec74d0399289317b5355e88",
            "input": "The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients.', '83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS\\xa0>\\xa014. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression.', 'Cytological atypia was more frequent in multiparous women (P\\xa0=\\xa00.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R\\xa0=\\xa00.204, P\\xa0=\\xa00.0417), higher number of births (R\\xa0=\\xa00.369, P\\xa0=\\xa00.0006), and estrogen receptor (ER) negativity of the index cancer (R\\xa0=\\xa0-0.203, P\\xa0=\\xa00.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R\\xa0=\\xa00.318, P\\xa0=\\xa00.0201), higher number of births (R\\xa0=\\xa00.382, P\\xa0=\\xa00.0004), and ER status (R\\xa0=\\xa0-0.314, P\\xa0=\\xa00.0038). Eight estrogen-regulated genes were increased in atypical samples (P\\xa0<\\xa00.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1.",
            "output": [
                "Is cytologic atypia in the contralateral unaffected breast related to parity and estrogen-related genes?"
            ]
        },
        {
            "id": "task847-68313eb1826f4763a47e210fc5fb2bc7",
            "input": "Childhood uveitis is a vision-threatening inflammatory eye disease commonly attributed to juvenile idiopathic arthritis (JIA). The pathogenesis is poorly understood, which makes clinical management challenging. We analyzed soluble mediators in ocular fluid (aqueous humor [AqH]) and serum from children with JIA-associated uveitis and common childhood uveitis to identify potential biomarkers and investigate the ocular microenvironment of this sight-threatening eye disease.', 'AqH (n\\u2009=\\u200973) and paired serum (n\\u2009=\\u200966) samples were analyzed for 51 soluble mediators of inflammation by multiplex immunoassay. Twenty-one children with JIA-associated uveitis were compared to 15 children with chronic anterior uveitis without arthritis, 29 children with noninfectious idiopathic uveitis, and 8 children with noninflammatory conditions (controls). For visualization of the joint effect of multiple mediators, we used the radial coordinate visualization (Radviz) method. Optimal biomarker level cutoffs were also determined.', 'The levels of interleukin-29 (IL-29)/interferon-\u03bb1 (IFN\u03bb1) were decreased (P\\u2009<\\u20090.001) and the levels of latency-associated peptide and osteoprotegerin were increased (P\\u2009=\\u20090.002 and P\\u2009=\\u20090.001, respectively) in samples of AqH, but not serum, from patients with JIA-associated uveitis. Multivariate analysis correcting for disease activity and treatment revealed that intraocular levels of IL-29/IFN\u03bb1 were specifically decreased in patients with JIA-associated uveitis as compared to those with idiopathic uveitis. Indeed, JIA-associated uveitis patients and idiopathic uveitis patients showed distinct profiles of intraocular soluble mediators. IL-29/IFN\u03bb1 showed a high area under the curve value (0.954), with 23.5 pg/ml as the optimal cutoff value.",
            "output": [
                "Does ocular Fluid Analysis in Children reveal Interleukin-29/Interferon-\u03bb1 as a Biomarker for Juvenile Idiopathic Arthritis-Associated Uveitis?"
            ]
        },
        {
            "id": "task847-95ee45dce5f949829874a3271d2edda5",
            "input": "Glucocorticoid receptor (GR) polymorphisms modulate glucocorticoid (GC) sensitivity and are associated with altered metabolic profiles.', \"To evaluate the presence of GR polymorphisms (BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), and 9\u03b2 (rs6198) and investigate their associations with metabolic alterations in patients in long-term remission of Cushing's syndrome (CS).\", 'Cross-sectional case-control study.', 'Sixty patients in long-term remission of CS were genotyped. Associations between GR polymorphisms and multiple vascular, body composition and metabolic parameters were investigated.', 'Allelic frequencies of the polymorphisms and their associations with several cardiometabolic risk factors.', 'This study shows that carriers of the 9\u03b2 polymorphism have a higher systolic blood pressure and lower resistin levels. The GC sensitizing BclI polymorphism is associated with an adverse cardiometabolic risk factor profile: higher fat percentages of extremities and legs, higher serum leptin and E-selectin levels, and higher intima media thickness in carriers versus non-carriers.",
            "output": [
                "Do glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing 's syndrome?"
            ]
        },
        {
            "id": "task847-82a30e32295640a6b531bd77f50a75f4",
            "input": "The present study aimed to investigate if eating disorder patients differ in specific personality traits depending on a positive screening of food addiction (FA) and to find a model to predict FA in eating disorder patients using measures of personality and impulsivity.', 'Two hundred seventy eight patients, having an eating disorder, self-reported on FA, impulsivity, personality, eating and general psychopathology. Patients were then split into two groups, depending on a positive or negative result on the FA screening. Analysis of variance was used to compare means between the two groups. Stepwise binary logistic regression was used to obtain a predictive model for the presence of FA.', 'Patients with FA had lower self-directedness, and more negative urgency and lack of perseverance than patients not reporting addictive eating. The probability of FA can be predicted by high negative urgency, high reward dependence, and low lack of premeditation.",
            "output": [
                "Is `` Food Addiction '' in Patients with Eating Disorders Associated with Negative Urgency and Difficulties to Focus on Long-Term Goals?"
            ]
        },
        {
            "id": "task847-2b4292b62d14465daae0e0c1d00c99f3",
            "input": "Although excessive sympathetic activation in viral myocarditis and the protective effects of sympathetic inhibition with \u03b2-blockers are clear, the effects of enhancing vagal tone on viral myocarditis remain unclear. In several models, vagus nerve activation with the \u03b17 nicotinic acetylcholine receptor (\u03b17-nAChR) agonists has been demonstrated to ameliorate inflammation. This study was therefore designed to examine the effects of cholinergic stimulation with \u03b17-nAChR agonist nicotine in a murine model of acute viral myocarditis.', 'BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine and methyllycaconitine (an \u03b17-nAChR antagonist) were administered at doses of 0.4mg/kg and 0.8mg/kg three times per day for 7 or 14 consecutive days, respectively. The effects of nicotine and methyllycaconitine on survival rate, myocardial histopathological changes, cardiac function, cytokine levels, viral RNA, malondialdehyde, and superoxide dismutase contents were investigated.', 'Nicotine significantly increased survival rate of the infected mice, decreased myocardial inflammation, and improved the impairment of left ventricular function in murine coxsackievirus B3-induced myocarditis compared with methyllycaconitine. The proinflammatory cytokines TNF-\u03b1, IL-1\u03b2, IL-6 and IL-17A were significantly decreased in the infected mice treated with nicotine compared with methyllycaconitine. Nicotine had no significant anti-oxidative and antiviral effects in coxsackievirus B3-infected mice.",
            "output": [
                "Does nicotine inhibit the production of proinflammatory cytokines of mice infected with coxsackievirus B3?"
            ]
        },
        {
            "id": "task847-d80972ac58cf41779b34eb5edc376725",
            "input": "An abnormal ratio of vasohibin-2/vasohibin-1 may be involved in the abnormal angiogenesis and vascular remodeling during pulmonary arterial hypertension (PAH).', 'To evaluate the pharmacological actions of Ponatinib (AP) in experimental model of PAH, the effects of AP on TGF-\u03b21-mediated endothelial-mesenchymal transition (EndoMT) in human pulmonary microvascular endothelial cells (HPMEC), and the hypoxic human pulmonary artery smooth muscle cells (HPASMC) proliferation and HPMEC in vitro, and on bleomycin (BLM)-induced PAH in vivo were investigated.', 'AP treatment resulted in a reduction of EndoMT in HPMECs with a decrease of vimentin, whereas an increase of VE-cadherin, reduction of fibroblast growth factor (FGF-2), vascular endothelial growth factor (VEGF) and vasohibin-2 (VASH-2), whereas an increase of vasohibin-1 (VASH-1) in the hypoxic HPMEC, a reduction of the HPASMC proliferation with decreases of wnt5a, \u03b2-catenin and cyclin D1 expression. AP ameliorated BLM-induced PAH in rats with reductions of FGF-2, VEGF, von Willebrand factor (vWF) and VASH-2 expression, whereas an increase of VASH-1 expression. AP ameliorated BLM-induced PAH in rats with reductions of the pathological score and the collagen deposition. In addition, AP ameliorated hemodynamics and right ventricular hypertrophy.",
            "output": [
                "Does ponatinib attenuate experimental pulmonary arterial hypertension by modulating Wnt signaling and vasohibin-2/vasohibin-1?"
            ]
        },
        {
            "id": "task847-5d9b3bc6037543dcbba46f04a63a2260",
            "input": "This study was undertaken to determine the effect of the topical application of diadenosine tetraphosphate on lactoferrin levels in rabbit tears.', 'Diadenosine tetraphosphate was topically instilled in a single-dose, tear samples were collected by micropipette and lactoferrin was measured by Enzyme-Linked ImmunoSorbent Assay (ELISA).', 'The concentration of lactoferrin in rabbit tears was significantly increased 1 h after diadenosine tetraphosphate application, remaining elevated for 3 h more. This effect was blocked by P2 receptors antagonists.",
            "output": [
                "Are lactoferrin Levels in Tears Increased by the Topical Application of Diadenosine Tetraphosphate?"
            ]
        },
        {
            "id": "task847-dc84dbd0f6de4ebb9e87b4b6a964b6d3",
            "input": "To investigate the expression and clinical significance of programmed cell death 4 (PDCD4), a novel metabolism-associated gene, during polycystic ovary syndrome (PCOS) pathogenesis.', 'Case-control study.', 'University hospital.', 'A total of 77 PCOS patients and 67 healthy women as matched controls.', 'PDCD4 expression in peripheral blood mononuclear cells analyzed by quantitative real-time polymerase chain reaction, and apoptosis of granulosa cells (GCs) detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and small-interfering RNA.', 'PDCD4 expression, body mass index (BMI), insulin 0, insulin 120, glucose 120, homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for \u03b2-cell function (HOMA-\u03b2), triglycerides, high-density lipoprotein (HDL), and GC apoptosis.', 'The PCOS patients had higher PDCD4 expression, but BMI was similar as matched with the obese group, which positively correlated with BMI, insulin 0, insulin 120, glucose 120, HOMA-IR, HOMA-\u03b2, triglycerides and negatively correlated with HDL (P<.05). After metformin treatment, PDCD4 expression was distinctly down-regulated for the obese women with PCOS with insulin resistance. Compared with the healthy controls, the apoptosis percentage of GCs was higher in the PCOS group and was decreased by knocking down PDCD4. Furthermore, expression of proapotosis factor Bax and the Bax/Bcl-2 ratio were lower, whereas the expression of antiapoptosis factor Bcl-2 was increased. In a multivariate logistic regression analysis, the level of PDCD4 expression independently related to the odds of PCOS risk after controlling for estradiol and insulin 120 (odds ratio 1.318).",
            "output": [
                "Is higher PDCD4 expression associated with obesity , insulin resistance , lipid metabolism disorders , and granulosa cell apoptosis in polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-a674b78a99c141d3a000e19488e07fe7",
            "input": "Hypertrophic scarring (HTS) is hypothesized to have a genetic mechanism, yet its genetic determinants are largely unknown. The mitogen-activated protein kinase (MAPK) pathways are important mediators of inflammatory signaling, and experimental evidence implicates MAPKs in HTS formation. We hypothesized that single-nucleotide polymorphisms (SNPs) in MAPK-pathway genes would be associated with severity of post-burn HTS.', 'We analyzed data from a prospective-cohort genome-wide association study of post-burn HTS. We included subjects with deep-partial-thickness burns admitted to our center who provided blood for genotyping and had at least one Vancouver Scar Scale (VSS) assessment. After adjusting for HTS risk factors and population stratification, we tested MAPK-pathway gene SNPs for association with the four VSS variables in a joint regression model. In addition to individual-SNP analysis, we performed gene-based association testing.', 'Our study population consisted of 538 adults (median age 40 years) who were predominantly White (76%) males (71%) admitted to our center from 2007-2014 with small-to-moderate-sized burns (median burn size 6% total body surface area). Of 2,146 SNPs tested, a rare missense variant in the PTPN5 gene (rs56234898; minor allele frequency 1.5%) was significantly associated with decreased severity of post-burn HTS (P = 1.3\u00d710-6). In gene-based analysis, PTPN5 (P = 1.2\u00d710-5) showed a significant association and BDNF (P = 9.5\u00d710-4) a borderline-significant association with HTS severity.",
            "output": [
                "Does missense Variant in MAPK Inactivator PTPN5 be Associated with Decreased Severity of Post-Burn Hypertrophic Scarring?"
            ]
        },
        {
            "id": "task847-608c0848762f4f09beff075cf8430a75",
            "input": "Women have poorer outcomes after vascular surgery as compared to men as shown by studies recently. Frailty is also an independent risk factor for postoperative morbidity and mortality. This study examines the interplay of gender and frailty on outcomes after infrainguinal vascular procedures.', 'The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all patients who underwent infrainguinal vascular procedures from 2005-2012. Frailty was measured using a modified frailty index (mFI; derived from the Canadian Study of Health and Aging). Univariate and multivariate analysis were performed to investigate the association of preoperative frailty and gender, on postoperative outcomes.', 'Of 24,645 patients (92% open, 8% endovascular), there were 533 deaths (2.2%) and 6198 (25.1%) major complications within 30 d postoperatively. Women were more frail (mean mFI = 0.269) than men (mean mFI = 0.259; P < 0.001). Women and frail patients (mFI>0.25) were more likely to have a major morbidity (P < 0.001) or mortality (P < 0.001) with the highest risk in frail women. On multivariate logistic regression analysis, female gender and increasing mFI were independently significantly associated with mortality (P < 0.05) as well as major complications. The interaction of gender and frailty in multivariate analysis showed the highest adjusted 30-d mortality and morbidity in frail females at 2.8% and 30.1%, respectively and that was significantly higher (P < 0.001) than nonfrail males, nonfrail females and frail males.",
            "output": [
                "Do gender and frailty predict poor outcomes in infrainguinal vascular surgery?"
            ]
        },
        {
            "id": "task847-cf3f264511444b7fa853ecad627e7904",
            "input": "Both the FRAX and Garvan calculators are used to estimate absolute risk of fracture, but they sometimes produce different estimates. We sought to determine which patient characteristics contribute to these discrepancies.', 'Ten-year hip fracture risk was estimated for 122 women, using both FRAX and Garvan with bone mineral density (BMD).', 'Differences in estimates of hip fracture were assessed, both in absolute terms and with respect to a treatment threshold of 3%.', 'Garvan estimates were higher than FRAX estimates across the range of ages and BMDs studied. A history of falls or of multiple fractures increased risk calculated by Garvan 3-6-fold, but did not account for all differences between calculators. Discrepancies around a 3% treatment threshold occurred in 31/122 (25%). Women aged 70-74 years, and women with osteopenia were most likely to have discordant estimates. Most discordant estimates (29/31) had a Garvan estimate \u2265 3% and FRAX\\u2009<3%. Falls, multiple fractures, ethnicity and a history of parental hip fracture contributed to some discordant estimates.",
            "output": [
                "Does reasons for discrepancies in hip fracture risk estimate using FRAX and Garvan calculators?"
            ]
        },
        {
            "id": "task847-19d12618afd6492199f37eb68dcbc6dd",
            "input": "Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with onset in childhood and is characterized by obsessions (recurrent, intrusive, persistent thoughts, impulses and/or ideas that often cause anxiety or distress) and compulsions (ritualized and stereotypic behaviours or mental acts that are often performed to relieve anxiety or distress associated with obsessions). Although OCD is a heritable disorder, its complex molecular etiology is poorly understood.', 'We combined enrichment analyses and an elaborate literature review of the top-ranked genes emerging from the 2 published genome-wide association studies of OCD and candidate genes implicated through other evidence in order to identify biological processes that, when dysregulated, increase the risk for OCD.', 'The resulting molecular protein landscape was enriched for proteins involved in regulating postsynaptic dendritic spine formation - and hence synaptic plasticity - through insulin-dependent molecular signalling cascades.",
            "output": [
                "Does an integrated molecular landscape implicate the regulation of dendritic spine formation through insulin-related signalling in obsessive-compulsive disorder?"
            ]
        },
        {
            "id": "task847-6ce2af7819f74b8f914b3999b574a72d",
            "input": "The cause of rheumatoid arthritis (RA) flares is multifactorial and not well understood. No reports of fractures influencing disease activity in patients with RA have been published. The purpose of this study was to determine whether fractures influence disease activity in patients with RA.', 'Hospital records of 470 patients with RA between 2011 and 2014 were analyzed. We first examined the incidence of flare using multiple regression analysis. Secondly, we examined the incidence of flare using DAS28-ESR, DAS28-CRP, and drug changes before bone fracture until bone union in the fracture cases.', 'Multiple linear regression analysis showed that female sex (p\\u2009<\\u20090.001), bottom DAS28-ESR (p\\u2009<\\u20090.001), and fracture (p\\u2009=\\u20090.041) were independent factor for DAS28-ESR at the last observation period, and sex (p\\u2009=\\u20090.040), bottom DAS28-CRP (p\\u2009<\\u20090.001), and fracture (p\\u2009=\\u20090.019) were independent factor for DAS28-CRP at the last observation period. The average DAS28-ESR value was significantly increased from 3.19 (prefracture) to 3.58 (bone union). The average DAS28-CRP value was also significantly increased from 2.45 (prefracture) to 2.79 (bone union).",
            "output": [
                "Do fractures lead to worsening of disease activity in rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-20e286380e85449bb312a920cb565d4c",
            "input": "MicroRNAs (miRNAs) play important roles in chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the regulation of miR-30a during such process has not yet been well understood. The aim of the study was to investigate the effects of miR-30a on chondrogenic differentiation of MSCs and explore the underlying mechanisms.', 'MSCs were isolated from rat bone marrow, and their immunophenotypes and multilineage differentiation potentials were identified. MiR-30a mimics or inhibitor were transfected into rat MSCs and SW1353 cells, respectively, and then the effects of miR-30a on chondrogenic differentiation were detected. The predicted target gene Delta-like 4 (DLL4, a ligand of the Notch signaling family) was verified by luciferase reporter assay, quantitative real time PCR and western blot.', \"MiR-30a was significantly up-regulated during chondrogenic differentiation of rat MSCs. Additionally, transfection of miR-30a mimics remarkably promoted the differentiation of rat MSCs into chondrocytes as evidence by the notably increased mRNA and protein expression levels of chondrogenic markers Collagen II and aggrecan as well as the enhanced alcian blue staining intensity, whereas inhibition of miR-30a obviously suppressed such process. Furthermore, during chondrogenesis, DLL4 expression was found to significantly decrease at both mRNA and protein levels, which was negatively regulated by miR-30a through directly targeting the 3'UTR of DLL4.",
            "output": [
                "Does microRNA-30a promote chondrogenic differentiation of mesenchymal stem cells through inhibiting Delta-like 4 expression?"
            ]
        },
        {
            "id": "task847-e60ebd1062c14793b3927e677c857757",
            "input": "Transient tachypnea of the newborn (TTN) is a benign disorder with a variable clinical course that often leads to hospitalization. The aim of this study was to assess and validate the relationship between the serum cystatin C level and symptom duration in infants with TTN.', 'Forty newborns presenting with TTN and who had undergone serum cystatin C (Cys C) tests on the first day of admission to the Kyung Hee University Hospital (Seoul, Korea) from 2009 to 2013 were included. The serum Cys C level, creatinine (Cr) level, estimated glomerular filtration rate (eGFR), and tachypnea duration were correlated retrospectively.', 'The median gestation period was 37.8\\xa0\u00b1\\xa03.8 weeks and the mean birth weight was 3.2\\xa0\u00b1\\xa00.4\\xa0kg. Tachypnea duration was 3.3\\xa0\u00b1\\xa02.0 days. Serum Cys C and Cr levels were 1.7\\xa0\u00b1\\xa00.2\\xa0mg/L and 0.8\\xa0\u00b1\\xa01.2\\xa0mg/dL, respectively. Tachypnea duration was significantly positively correlated with the serum levels of Cys C and significantly negatively correlated with Cys C-based eGFR (p\\xa0=\\xa00.016), but was not significantly correlated with the serum Cr level or Cr-based eGFR. When tachypnea duration was compared between infants with Cys C level <1.6\\xa0mg/L (n\\xa0=\\xa015; Group A) and infants with Cys C level\\xa0\u2265\\xa01.6\\xa0mg/L (n\\xa0=\\xa025; Group B), the symptom duration was significantly shorter in Group A infants (p\\xa0=\\xa00.011).",
            "output": [
                "Does decreased Cystatin C-Estimated Glomerular Filtration Rate be Correlated with Prolonged Hospital Stay in Transient Tachypnea of Newborn Infants?"
            ]
        },
        {
            "id": "task847-ea470d032a7942c0814d4e549ad1fa21",
            "input": "The majority of acute coronary syndromes are caused by plaque ruptures. Proteases secreted by macrophages play an important role in plaque ruptures by degrading extracellular matrix proteins in the fibrous cap. Matrix metalloproteinases have been shown to be markers for cardiovascular disease whereas the members of the cathepsin protease family are less studied.', 'Cathepsin D, cathepsin L and cystatin B were measured in plasma at baseline from 384 individuals who developed coronary events (CEs), and from 409 age-matched and sex-matched controls from the Malm\u00f6 Diet and Cancer cardiovascular cohort.', 'Cathepsin D (180 (142-238) vs 163 (128-210), p<0.001), cathepsin L (55 (44-73) vs 52 (43-67), p<0.05) and cystatin B levels (45 (36-57) vs 42 (33-52), p<0.001) were significantly increased in CE cases compared to controls. In addition, increased cathepsin D (220 (165-313) vs 167 (133-211), p<0.001), cathepsin L (61 (46-80) vs 53 (43-68), p<0.05) and cystatin B (46 (38-58) vs 43 (34-54), p<0.05) were associated with prevalent diabetes. Furthermore, cathepsin D and cystatin B were increased in smokers. The HRs for incident CE comparing the highest to the lowest tertile(s) of cathepsin D and cystatin B were 1.34 (95% CI 1.02 to 1.75) and 1.26 (95% CI 1.01 to 1.57), respectively, after adjusting for age, sex, low-density lipoprotein/high-density lipoprotein ratio, triglycerides, body mass index, hypertension and glucose, but these associations did not remain significant after further addition of smoking to the model. In addition, cathepsin D was increased in incident CE cases among smokers after adjusting for cardiovascular risk factors.",
            "output": [
                "Are high levels of cathepsin D and cystatin B associated with increased risk of coronary events?"
            ]
        },
        {
            "id": "task847-4fe34b27904d4763ae88aa72f270afc4",
            "input": "The MacNew questionnaire is a neuro-behavioral tool which is easy and immediately usable. This self-reported questionnaire filled out by the patient allows the physician to achieve helpful information concerning the ways for optimizing the therapy and patient's lifestyles. In this retrospective study, our aim was to assess whether relatively high scores found using the MacNew questionnaire in patients who had undergone percutaneous or surgical revascularization were associated with a decreased risk of unscheduled hospitalizations during the follow-up.\", 'A retrospective analysis concerning 210 patients was carried out. The clinical sheets of these patients were examined as regards the information provided in the specific questionnaires (MacNew Italian version) routinely administered during the hospitalization prescribed for recovering from recent interventions of coronary percutaneous or surgery revascularization. Every patient undergoing the psychological test with MacNew questionnaire was followed up for 3 years.', \"Using univariate analysis, a global score's high value (i.e., above the median of the whole examined population) was shown to be associated with a significantly decreased risk of rehospitalization (HR (hazard ratio): 0.4312; 95% CI: 0.3463 - 0.5370; P < 0.0001). After adjustment for age, gender and myocardial infarction as initiating event, using a multivariate Cox proportional hazards regression model, the protection exerted by a high MacNew score against the risk of hospitalizations remained significant (HR: 0.0885; 95% CI: 0.0317 - 0.2472; P < 0.0001).",
            "output": [
                "Does the MacNew Questionnaire be a Helpful Tool for Predicting Unplanned Hospital Readmissions After Coronary Revascularization?"
            ]
        },
        {
            "id": "task847-ba908c23be5a4621a9defaee1274b1b2",
            "input": "Tumor necrosis factor-\u03b1 converting enzyme (TACE) has been demonstrated to be involved in liver inflammation. However, the significance of TACE methylation in acute-on-chronic hepatitis B liver failure (ACHBLF) has not been demonstrated. This study aims to evaluate TACE methylation status in ACHBLF and determine its predictive value for prognosis.', 'Forty-five patients with ACHBLF, 80 with chronic hepatitis\\xa0B (CHB) and 54 healthy controls (HCs) were enrolled. The methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The TACE mRNA expression was determined by quantitative real-time polymerase chain reaction. The plasma levels of TACE, TNF-\u03b1, sTNFRI, sTNFRII were measured by enzyme-linked immunosorbent assay.', 'TACE methylation was significantly lower in patients with ACHBLF than those with CHB (\u03c7(2)=24.69, P<0.01) and HCs (\u03c7(2)=35.93, P<0.01). Meanwhile, TACE methylation was significantly lower in CHB patients than HCs (\u03c7(2)=4.03, P<0.05). TACE methylation was significantly inversely associated with its mRNA expression (r=-0.68; P<0.01). The plasma levels of TACE, TNF-\u03b1, sTNFRI, sTNFRII were significantly higher in patients with ACHBLF than those with CHB (P<0.05, respectively) and HCs (P<0.05, respectively). In patients with ACHBLF, significantly higher prothrombin activity, lower total bilirubin and MELD score were found in TACE methylated group than unmethylated group (P<0.05). ACHBLF patients with methylated TACE showed significantly better survival than those without (P<0.01).",
            "output": [
                "Does demethylation of tumor necrosis factor-\u03b1 converting enzyme predict poor prognosis in acute-on-chronic hepatitis B liver failure?"
            ]
        },
        {
            "id": "task847-3e8ca52361be4af2b26761c27306a5c4",
            "input": "Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has been reported to be involved in several tumors, whether it participates in colorectal cancer (CRC) progression remains unclear. Here, we investigated the biological function and underlying molecular mechanisms of LRG1 in CRC.', 'The mRNA and protein levels of LRG1 were assessed in CRC tissues through RT-PCR and immunohistochemistry, respectively. HCT116 and SW480 cells were treated with LRG1 siRNA, control siRNA, or recombinant LRG1. Transwell invasion assays and wound healing assays were performed to evaluate the invasion and migration of CRC cells. Epithelial-to-mesenchymal transition (EMT) markers of E-cadherin, VDR, N-cadherin, \u03b1-SMA, Vimentin and Twist1 were detected by RT-PCR and western blot. Enzyme-linked immunosorbent assay was used to measure the secretion level of VEGF-A. Conditioned medium from CRC cells was collected for endothelial cell migration, tube formation and aortic ring sprouting assays.', 'LRG1 was overexpressed in CRC tissues and associated with cancer aggressiveness. LRG1 was further found to induce the EMT process, as well as CRC cell migration and invasion capacity. In addition, LRG1 promoted VEGF-A expression in CRC cells and contributed to tumor angiogenesis. Furthermore, HIF-1\u03b1 could be induced by LRG1 in a concentration- and time-dependent manner, which was responsible for LRG1-induced VEGF-A expression and EMT.",
            "output": [
                "Does lRG1 modulate epithelial-mesenchymal transition and angiogenesis in colorectal cancer via HIF-1\u03b1 activation?"
            ]
        },
        {
            "id": "task847-26102686c6d742b59698ed0844cb3473",
            "input": "The author addresses whether the face bow is irrelevant for all types of prosthetic work and for planning orthognathic surgery.', 'The author searched electronic databases to find studies whose investigators used the strongest clinical evidence (that is, randomized clinical trials) and studies whose investigators incorporated the use of cinefluorography. The author found 13 studies and 1 Internet video that provided strong evidence to support the irrelevancy of the face bow transfer.', 'Evidence indicates that the face bow has nothing\\xa0to do with speech, the fit and comfort of the prostheses, ridge morphology, facial contours, the color of\\xa0the teeth and denture bases, the arrangement of the artificial teeth, chewing efficiency stability, and the psychological aspects of prosthodontic treatment. The cinefluorographic example showed that there was no condylar axis\\xa0of rotation\\xa0during functional activity, a sawing action of the\\xa0mandibular incisors during the incising of\\xa0toast and\\xa0the\\xa0mandible moving in a back and forth,\\xa0rocking\\xa0chair-like movement during functional activity.",
            "output": [
                "Is the face bow irrelevant for making prostheses and planning orthognathic surgery?"
            ]
        },
        {
            "id": "task847-101b8f57d23143a385acb9ccb8f46f23",
            "input": "Dexamethasone is frequently used for the treatment of postoperative nausea and vomiting and as an adjunct in multimodal postoperative analgesia after total joint arthroplasty; however, the incidence of periprosthetic joint infection (PJI) after the use of perioperative dexamethasone in total joint arthroplasty has yet to be fully elucidated.', \"A retrospective chart review was conducted of all patients who underwent total hip or knee arthroplasty (N\\xa0= 6294) between January 1, 2002 and January 31, 2014. The primary outcome was PJI requiring surgical intervention. Patients were subdivided into 2 cohorts; patients who received perioperative dexamethasone, a single 4- to 10-mg intravenous dose, as prophylaxis against postoperative nausea and vomiting (Dex group; N\\xa0= 557) and those that did not receive perioperative dexamethasone (No Dex group; N\\xa0= 5737). Secondary measures included timing of infection, culture data, and the type and number of subsequent procedures. Statistical analysis was performed using a chi-square or Fisher's exact test where appropriate.\", 'Seventy-four joints of the 6294 joints included in this analysis ultimately developed a PJI for an overall incidence of infection of 1.2%. Seven of the 557 joints (1.3%) in the Dex group developed a PJI; 67 of the 5737 joints (1.2%) in the No Dex group developed an infection. This difference was not significant (P\\xa0= .8022). No significant difference in the timing of infection or the number of subsequent procedures was seen.",
            "output": [
                "Does perioperative Dexamethasone Administration Increase the Incidence of Postoperative Infection in Total Hip and Knee Arthroplasty : A Retrospective Analysis?"
            ]
        },
        {
            "id": "task847-654e2afe392c4ccca58391adcdfd88e7",
            "input": "When given in conjunction with surgery for treating cancer, radiation therapy may result in impaired wound healing, which, in turn, could cause skin ulcers. In this study, bilayer and monolayer autologous skin substitutes were used to treat an irradiated wound.', 'A single dose of 30 Gy of linear electron beam radiation was applied to the hind limb of nude mice before creating the skin lesion (area of 78.6 mm). Monolayer tissue-engineered skin substitutes (MTESSs) were prepared by entrapping cultured keratinocytes in fibrin matrix, and bilayer tissue-engineered skin substitutes (BTESSs) were prepared by entrapping keratinocytes and fibroblasts in separate layers. Bilayer tissue-engineered skin substitute and MTESS were implanted to the wound area. Gross appearance and wound area were analyzed to evaluate wound healing efficiency. Skin regeneration and morphological appearance were observed via histological and electron microscopy. Protein expressions of transforming growth factor \u03b21 (TGF-\u03b21), platelet-derived growth factor BB (PDGF-BB), and vascular endothelial growth factor (VEGF) in skin regeneration were evaluated by immunohistochemistry (IHC).', 'Macroscopic observation revealed that at day 13, treatments with BTESS completely healed the irradiated wound, whereas wound sizes of 1.1 \u00b1 0.05 and 6.8 \u00b1 0.14 mm were measured in the MTESS-treated and untreated control groups, respectively. Hematoxylin-eosin (H&E) analysis showed formation of compact and organized epidermal and dermal layers in the BTESS-treated group, as compared with MTESS-treated and untreated control groups. Ultrastructural analysis indicates maturation of skin in BTESS-treated wound evidenced by formation of intermediate filament bundles in the dermal layer and low intercellular space in the epidermal layer. Expressions of TGF-\u03b21, PDGF-BB, and VEGF were also higher in BTESS-treated wounds, compared with MTESS-treated wounds.",
            "output": [
                "Does tissue-Engineered Skin Substitute enhance Wound Healing after Radiation Therapy?"
            ]
        },
        {
            "id": "task847-7d8b95b2d4c34a8eaa1c4eec7ca01a56",
            "input": "There is controversy on the effects of the non-ionizing radiation emitted by cell phones on cellular processes and the impact of such radiation exposure on health. The purpose of this study was to investigate whether cell phone use alters cytokine expression in the saliva produced by the parotid glands.', 'Cytokine expression profile was determined by enzyme linked immuno sorbent assay (ELISA) in the saliva produced by the parotid glands in healthy volunteers, and correlated with self-reported cell phone use and laterality.', 'The following parameters were determined, in 83 Brazilian individuals in saliva produced by the parotid glands comparing the saliva from the gland exposed to cell phone radiation (ipsilateral) to that from the contralateral parotid: salivary flow, total protein concentration, interleukin 1 \u03b2 (IL-1 \u03b2), interleukin 6 (IL-6), interleukin 10 (IL-10), interferon \u03b3 (IFN-\u03b3), and tumor necrosis factor \u03b1 (TNF-\u03b1) salivary levels by ELISA. After multiple testing correction, decreased IL-10 and increased IL-1\u03b2 salivary levels in the ipsilateral side compared with the contralateral side (P < 0.05) were detected. Subjects who used cell phones for more than 10 years presented higher differences between IL-10 levels in ipsilateral versus contralateral parotids (P = 0.0012). No difference was observed in any of the tested parameters in correlation with cell phone monthly usage in minutes.",
            "output": [
                "Is cell phone use associated with an inflammatory cytokine profile of parotid gland saliva?"
            ]
        },
        {
            "id": "task847-66c9f73bbc6d4bf5bf4c983675960272",
            "input": "Maternal-fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was recently recognized as a lyso-phospholipid (lyso-PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers.', 'Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 GDM-diet, 20 GDM-insulin). Fetal ultrasound was performed at gestational week 38. At delivery, maternal and neonatal anthropometry was performed, and fatty acids in total lipids and phospholipid species were analyzed in placenta, maternal and venous cord blood. Western-blot analyses were performed for placental fatty acid carriers.', 'Fetal abdominal circumference z-score at 38 weeks tended to higher values in GDM (P\\xa0=\\xa00.071), pointing toward higher fetal fat accretion in these babies. DHA percentage in cord serum total lipids (P\\xa0=\\xa00.029) and lyso-PL (P\\xa0=\\xa00.169) were reduced in GDM. Placental MFSD2a was reduced in both GDM groups and was positively correlated to DHA values in cord serum total lipids (r\\xa0=\\xa00.388, P\\xa0=\\xa00.003). Among established placental lipid carriers, only FATP4 was correlated to DHA concentration in placental lyso-PL. In all compartments, DHA percentage was inversely correlated to fetal abdominal circumference.",
            "output": [
                "Is placental MFSD2a transporter related to decreased DHA in cord blood of women with treated gestational diabetes?"
            ]
        },
        {
            "id": "task847-9335bd1171e145d8a885b39ada59d78c",
            "input": "This study aimed to investigate the effects of branched-chain amino acid (BCAA) supplementation on recovery of power-producing ability following a strength training (ST) session.', 'Eleven resistance-trained males, performed baseline measures of a countermovement jump (CMJ) and a seated shot-put throw (SSPT). In a counterbalanced fashion, participants were provided with either 20-g of BCAA or a placebo. Each dose was divided into two equal quantities and consumed before and after a ST session consisting of various multi-joint barbell exercises. For both conditions, the CMJ and SSPT were repeated at 24-h post-ST, in addition participants attributed their perceived muscle soreness level via a 200-mm visual analogue scale.', 'Following ST there were significant decrements in CMJ (Baseline; 55.2 \u00b1 7.4-cm, BCAA; 52.8 \u00b1 5.9-cm Placebo; 50.6 \u00b1 7.3-cm) and SSPT (Baseline; 4.55 \u00b1 0.56-m, BCAA; 4.37 \u00b1 0.61-m, Placebo; 4.22 \u00b1 0.64- m) for both conditions in comparison to baseline values (P < 0.05). However, BCAA was shown to attenuate the decrements in CMJ and SSPT performance compared to placebo (P < 0.05). Muscle soreness was significantly increased following ST for both conditions, however there were no differences in attributed values following BCAA and placebo ingestion.",
            "output": [
                "Does branched-chain amino acid supplementation attenuate a decrease in power-producing ability following acute strength training?"
            ]
        },
        {
            "id": "task847-701f95be23014bfd805741481dfa25b1",
            "input": "Receptor for advanced glycation end products (RAGE) is abundantly expressed on alveolar epithelial cells (AECs) and participates in innate immune responses such as apoptosis and inflammation. However, it is unclear whether RAGE-mediated apoptosis of AECs is associated with hyperoxia-induced lung injury.', 'We used wild-type and RAGE-knockout C57BL6/J mice in this study. In addition, we developed bone marrow chimeric mouse models expressing RAGE on hematopoietic or non-hematopoietic cells, including lung parenchymal cells, and compared survival ratios and changes in the permeability of the alveolar-capillary barrier after hyperoxia exposure. Further, we prepared single cell suspensions of lung cells and evaluated the apoptosis of AECs or microvascular endothelial cells (MVECs) by using a combination of antibodies and JC-1 dye. We also examined whether RAGE inhibition decreased hyperoxia-induced apoptosis of human lung epithelial cells in vitro.', 'After hyperoxia exposure, mice expressing RAGE on lung cells showed lower survival rate and increased alveolar-capillary permeability than mice expressing RAGE on hematopoietic cells. RAGE-expressing AECs showed significantly higher apoptosis than RAGE-knockout AECs after in vivo hyperoxia exposure. The level of hyperoxia-induced apoptosis was not different in MVECs. However, RAGE-null lung epithelial cells showed lower apoptosis than RAGE-expressing cells in vitro.",
            "output": [
                "Is receptor for advanced glycation end products expressed on alveolar epithelial cells the main target for hyperoxia-induced lung injury?"
            ]
        },
        {
            "id": "task847-3f738963435640b7ab880fe8f1efede1",
            "input": "Lymph node (LN) involvement represents the strongest prognostic factor in colon cancer patients. The objective of this prospective study was to assess the prognostic impact of isolated tumor cells (ITC, defined as cell deposits \u2264 0.2 mm) in loco-regional LN of stage I & II colon cancer patients.', 'Seventy-four stage I & II colon cancer patients were prospectively enrolled in the present study. LN at high risk of harboring ITC were identified via an in vivo sentinel lymph node procedure and analyzed with multilevel sectioning, conventional H&E and immunohistochemical CK-19 staining. The impact of ITC on survival was assessed using Cox regression analyses.', 'Median follow-up was 4.6 years. ITC were detected in locoregional lymph nodes of 23 patients (31.1%). The presence of ITC was associated with a significantly worse disease-free survival (hazard ratio = 4.73, p = 0.005). Similarly, ITC were associated with significantly worse overall survival (hazard ratio = 3.50, p = 0.043).",
            "output": [
                "Are isolated tumor cells in stage I & II colon cancer patients associated with significantly worse disease-free and overall survival?"
            ]
        },
        {
            "id": "task847-59f167cb50fc4d9ebc978c1b277f3d65",
            "input": "Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear.', 'We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls.', 'HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual.",
            "output": [
                "Does human papillomavirus vaccination induce neutralising antibodies in oral mucosal fluids?"
            ]
        },
        {
            "id": "task847-7e6d17d618c04ac280810cc21714db1d",
            "input": "Decompressive hemicraniectomy (DHC) reduces mortality and improves outcome after malignant middle cerebral artery infarction (MMI) but early in-hospital mortality remains high between 22 and 33%. Possibly, this circumstance is driven by cerebral herniation due to space-occupying brain swelling despite decompressive surgery. As the size of the removed bone flap may vary considerably between surgeons, a size too small could foster herniation. Here, we investigated the effect of the additional volume created by an extended DHC (eDHC) on early in-hospital mortality in patients suffering from MMI.', 'We performed a retrospective single-center cohort study of 97 patients with MMI that were treated either with eDHC (n = 40) or standard DHC (sDHC; n = 57) between January 2006 and June 2012. The primary study end point was defined as in-hospital mortality due to transtentorial herniation.', 'In-hospital mortality due to transtentorial herniation was significantly lower after eDHC (0 vs. 11%; p = 0.04), which was paralleled by a significantly larger volume of the craniectomy (p < 0.001) and less cerebral swelling (eDHC 21% vs. sDHC 25%; p = 0.03). No statistically significant differences were found in surgical or non-surgical complications and postoperative intensive care treatment.",
            "output": [
                "Does large Size Hemicraniectomy reduce Early Herniation in Malignant Middle Cerebral Artery Infarction?"
            ]
        },
        {
            "id": "task847-bb98619a488f474abb85e43a6fe12ec3",
            "input": "Pseudohypoparathyroidism (PHP) is a genetic disorder characterized by resistance to the peripheral action of PTH due to maternally inherited heterozygous inactivating mutations in the coding sequence of Gs\u03b1 or intronic regions of GNAS leading to aberrant splice variants (PHP1A), or methylation defects at GNAS (PHP1B). Brachydactyly is a clinical feature associated with both PHP1A and PHP1B, although it is more frequent in PHP1A patients. Loss-of-function mutations in PTHLH, the gene coding for parathyroid hormone related protein (PTHrP) were previously described in some patients with brachydactyly. Primary failure of tooth eruption (PFE) is related to some syndromes involving skeletal development, but it is also known as a nonsyndromic autosomal dominant condition. Previous studies showed that familial nonsyndromic PFE is caused by heterozygous mutations in the gene encoding the G protein-coupled receptor (PTH1R) for PTH and PTHrP. Thus, we hypothesized that PTHrP resistance could result in failure of tooth eruption (FTE) and/or brachydactyly in PHP.', 'Nineteen patients with a molecular diagnosis of PHP underwent dental panoramic radiography (DPR), hand radiography and had their PTHrP levels measured. Patients with alterations at DPR were submitted to clinical dental evaluation.', 'Nine patients had FTE and 7 patients had brachydactyly; 4 patients presented both features and none of them presented high PTHrP levels. Fourteen patients had PTHrP levels within the normal range and only one patient had slightly elevated PTHrP levels. Additionally, three novel GNAS mutations were described.",
            "output": [
                "Are failure of tooth eruption and brachydactyly in pseudohypoparathyroidism related to plasma parathyroid hormone-related protein levels?"
            ]
        },
        {
            "id": "task847-c165a654f54b44469213c247489db7fa",
            "input": "To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation.', 'Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3-59, and 38 sex- and age-matched controls; 3 patients with 11\u03b2-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies.', 'We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3\u03b2-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals.', 'Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11\u03b2-hydroxyandrostenedione, 11-ketoandrostenedione 11\u03b2-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11\u03b2-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals.",
            "output": [
                "Are adrenal-derived 11-oxygenated 19-carbon steroids the dominant androgens in classic 21-hydroxylase deficiency?"
            ]
        },
        {
            "id": "task847-f2063d9e256f4208b032f894242a17d4",
            "input": "Primary hyperparathyroidism is usually characterized by a monoclonal parathyroid tumor secreting excess parathyroid hormone (PTH). The main regulator of PTH secretion is calcium and the calcium-PTH set point is shifted in parathyroid tumor cells. We sought to investigate the relationship between tumor PTH and PTH mRNA expression and clinical presentation as well as the regulatory factors including phosphate, vitamin D, and fibroblast growth factor 23.', 'A total of 154 parathyroid tumors were analyzed by PTH immunohistochemistry and chromogenic in situ hybridization of PTH mRNA. A subset of samples (n = 34) was analyzed using quantitative real-time PCR.', 'Low tumor PTH mRNA level was significantly associated with low tumor PTH immunoreactivity (P = 0.026), but the two did not correlate with regard to histological distribution within individual tumors. Tumors displaying reduced PTH mRNA levels as compared with normal rim were significantly larger (P = 0.013) and showed higher expression of the calcium-sensing receptor (CASR) (P = 0.046). Weaker tumor PTH mRNA level was significantly associated with higher concentration of circulating 25-hydroxyvitamin D (P = 0.005). No significant correlation was seen between PTH immunoreactivity and patient biochemistry. Tumor weight was strongly associated with circulatory concentrations of calcium and PTH.",
            "output": [
                "Does diffuse parathyroid hormone expression in parathyroid tumors argue against important functional tumor subclones?"
            ]
        },
        {
            "id": "task847-8b47b91e634d4d78a58d37188bf1992e",
            "input": "Williams syndrome (WS), a genetic disorder resulting from hemizygous microdeletion of chromosome 7q11.23, has emerged as a model for identifying the genetic architecture of socioemotional behavior. Common polymorphisms in GTF2I, which is found within the WS microdeletion, have been associated with reduced social anxiety in the general population. Identifying neural phenotypes affected by these polymorphisms would help advance our understanding not only of this specific genetic association but also of the broader neurogenetic mechanisms of variability in socioemotional behavior.', 'Through an ongoing parent protocol, the Duke Neurogenetics Study, we measured threat-related amygdala reactivity to fearful and angry facial expressions using functional magnetic resonance imaging, assessed trait personality using the Revised NEO Personality Inventory, and imputed GTF2I rs13227433 from saliva-derived DNA using custom Illumina arrays. Participants included 808 non-Hispanic Caucasian, African American, and Asian university students.', 'The GTF2I rs13227433 AA genotype, previously associated with lower social anxiety, predicted decreased threat-related amygdala reactivity. An indirect effect of GTF2I genotype on the warmth facet of extraversion was mediated by decreased threat-related amygdala reactivity in women but not men.",
            "output": [
                "Does a Common Polymorphism in a Williams Syndrome Gene predict Amygdala Reactivity and Extraversion in Healthy Adults?"
            ]
        },
        {
            "id": "task847-46fef51cebf44e1eaee27a98ecfccc42",
            "input": "To calculate the prevalence of long term catheter use in the community in two areas in the south and west of England.', 'People in England register with general practices to access health care through a National Health Service. Catheters are provided by prescription free of charge. In 2008, patients using urinary catheters for over 3 months were identified, and demographic information collected, from databases of general practices, using catheter prescribing records. The age and sex distributions of people in each practice were obtained from capitation claims. Overall, and age and sex-specific prevalence were calculated separately for each area, and compared.', 'A total of 583 long term catheter users (329 south, 254 west) were identified from 404,328 people registered with practices. The overall population prevalence is similar in both locations (0.146% southern, 0.141% western). Extrapolating for the United Kingdom, this is over 90,000 long term catheter users. Prevalence increases with age (0.732% in over 70 years, 1.224% over 80), especially amongst men. Overall, higher proportions have neurological (vs. non-neurological) reasons (62.9% vs. 37.1%) and use urethral (vs. suprapubic) catheters (59.7% vs. 40.3%). Compared to men, more women tend to use suprapubic (56.4% vs. 29.3%) and have a catheter for neurological reasons (71.8% vs. 56.2%, P\\u2009=\\u20090.053).",
            "output": [
                "Do community prevalence of long-term urinary catheters use in England?"
            ]
        },
        {
            "id": "task847-16d35d7123fa4c7493f8039cc4c09c1a",
            "input": "The objective of this study was to determine the utility of subjective memory decline (SMD) to predict episodic memory change and rates of clinical progression in cognitively normal older adults with evidence of high \u03b2-amyloid burden (CN A\u03b2+).', 'Fifty-eight CN A\u03b2+ participants from the Australian Imaging, Biomarkers, and Lifestyle study responded to an SMD questionnaire and underwent comprehensive neuropsychological assessments. Participant data for three follow-up assessments were analyzed.', \"In CN A\u03b2+, subjects with high SMD did not exhibit significantly greater episodic memory decline than those with low SMD. High SMD was related to greater rates of progression to mild cognitive impairment or Alzheimer's disease (AD) dementia (hazard ratio\\xa0=\\xa05.1; 95% confidence interval, 1.4-20.0, P\\xa0=\\xa0.02) compared with low SMD. High SMD was associated with greater depressive symptomatology and smaller left hippocampal volume.",
            "output": [
                "Does subjective memory decline predict greater rates of clinical progression in preclinical Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-0ca51580727944998d16b86958e85cb5",
            "input": "Inter-tissue molecular interactions are critical to the function and behavior of biological systems in multicellular organisms, but systematic studies of interactions between tissues are lacking. Also, existing studies of inter-tissue interactions are based on direct gene expression correlations, which can't distinguish correlations due to common genetic architectures versus biochemical or molecular signal exchange between tissues.\", 'We developed a novel strategy to study inter-tissue interaction by removing effects of genetic regulation of gene expression (genetic decorrelation). We applied our method to the comprehensive atlas of gene expression across nine human tissues in the Genotype-Tissue Expression (GTEx) project to generate novel genetically decorrelated inter-tissue networks. From this we derived modules of genes important in inter-tissue interactions that are likely driven by biological signal exchange instead of their common genetic basis. Importantly we highlighted communication between tissues and elucidated gene activities in one tissue inducing gene expression changes in others.', 'We reveal global unidirectional inter-tissue coordination of specific biological pathways such as protein synthesis. Using our data, we highlighted a clinically relevant example whereby heart expression of DPP4 was coordinated with a gene expression signature characteristic for whole blood proliferation, potentially impacting peripheral stem cell mobilization. We also showed that expression of the poorly characterized FOCAD in heart correlated with protein biosynthetic processes in the lung.",
            "output": [
                "Does inter-tissue coexpression network analysis reveal DPP4 as an important gene in heart to blood communication?"
            ]
        },
        {
            "id": "task847-b1aea96cb79e4b50bd1c2448abacfd7d",
            "input": "The high glucose concentration observed in diabetic patients is a recognized factor of mitochondrial damage in various cell types. Its impact on mitochondrial bioenergetics in blood platelets remains largely vague. The aim of the study was to determine how the metabolism of carbohydrates, which has been impaired by streptozotocin-induced diabetes may affect the functioning of platelet mitochondria.', 'Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Platelet mitochondrial respiratory capacity was monitored as oxygen consumption (high-resolution respirometry). Mitochondrial membrane potential was assessed using a fluorescent probe, JC-1. Activation of circulating platelets was monitored by flow cytometry measuring of the expressions of CD61 and CD62P on a blood platelet surface. To determine mitochondrial protein density in platelets, Western Blot technique was used.', 'The results indicate significantly elevated mitochondria mass, increased mitochondrial membrane potential (\u0394\u03a8m) and enhanced respiration in STZ-diabetic animals, although the respiration control ratios appear to remain unchanged. Higher \u0394\u03a8m and elevated mitochondrial respiration were closely related to the excessive activation of circulating platelets in diabetic animals.",
            "output": [
                "Are higher mitochondrial potential and elevated mitochondrial respiration associated with excessive activation of blood platelets in diabetic rats?"
            ]
        },
        {
            "id": "task847-96f26c779ccb4dc8b956799d5f669994",
            "input": "To analyse prospectively results of HAL-RAR technique by evaluating pain, perioperative complications and clinical outcome after two years followup.', 'A prospective study design including 30 consecutive patients with haemorrhoids grade III-IV treated from June 2012. After discharge, patients received a specific questionnaire to record postoperative pain, delayed complications, evolution/disappearance of the symptoms that led to the surgical intervention (bleeding, prolapse, itching, pain and soiling). A visual analog scale (VAS) was used to measure pain. Outpatient follow-up was carried out at 7 days, and 1, 6 and 12 months and annually thereafter. Pre, intra and postoperative data (including physical examination) had been recorded prospectively.', 'The median operating time (range) was 40 (26-60) minutes. Average hospital stay (range) was 11 (3-25) hours. No postoperative complications were observed in 29 cases (96.6%). Median follow-up was 26 (12-36) months. All the patients attended the follow-up. Mean postoperative pain was VAS\\xa0=\\xa01.7 on the seventh day and it was practically non-existent (VAS\\xa0=\\xa00.7) 1 month after the procedure. 87.5% of patients confirmed complete relief of symptoms after 30 days and 93% of patients feel free of symptoms 6 months after the procedure. No patient has experienced late complications as dyschezia, urgency, soiling or faecal incontinence. After 24 months follow-up, recurrence of bleeding and prolapse was observed in only 1 patient; 93% of patients have considered results of HAL-RAR as very good or excellent.",
            "output": [
                "Is hAL-RAR ( Doppler guided haemorrhoid artery ligation with recto-anal repair ) a safe and effective procedure for haemorrhoids . Results of a prospective study after two-years follow-up?"
            ]
        },
        {
            "id": "task847-1ea00a353b4f41a7a66dabf93b3a3274",
            "input": "Gastric cancer is the third leading cause of cancer-related deaths in the world with high mortality rate due to the lack of markers in early detection and effective therapies. MicroRNAs (miRNAs), a critical part of epigenetic regulations in tumor, have been shown to be closely related to the initiation, development, invasion, metastasis and prognosis of gastric cancer. The present study aims to investigate the expression of miR-1290 in gastric tumor cells and to elucidate the target gene of miR-1290 in SGC-7901 gastric cancer cells.', 'The fluorescence in situ hybridization, real time PCR and Western blot were used to investigate the expression of miR-1290 in gastric tumor cells and clinical gastric tumor samples. The effect of miR-1290 expression on gastric tumor cells was studied using Synthetic miR-1290 inhibitor transfection, in vitro wound healing assay and flow cytometry analysis. Bioinformatics and Luciferase reporter assay were used to predict and validate the target gene of miR-1290.', 'Our results revealed that miR-1290 was highly expressed in SGC-7901 gastric cancer cells as well as in clinical gastric cancer samples, which was correlated with clinical stages, depth of invasion and lymph node metastasis. Synthetic miR-1290 inhibitor transfection significantly inhibited the proliferation and migration of SGC-7901 cells. Bioinformatics analysis and luciferase reporter assay suggested that miR-1290 functioned in gastric cancer cells by targeting FOXA1 gene.",
            "output": [
                "Does sMicroRNA-1290 inhibit cells proliferation and migration by targeting FOXA1 in gastric cancer cells?"
            ]
        },
        {
            "id": "task847-3057e02a455046cc923de3103db0279e",
            "input": "Objectives: To determine the level of coagulation factors and inherited inhibitors in Fresh Frozen Plasma (FFP) and to evaluate Prothrombin Time and activated partial thrombin time in fresh frozen plasma.', 'Cross-sectional study.', 'Jomo Kenyatta University of Agriculture and Technology in Medical Laboratory Sciences.', 'Eighteen blood bags collected from voluntary blood donors.', 'Coagulation factors and inhibitors levels, Prothrombin Time (PT) and Activated Partial thrombin Time (APTT) remained within the reference range requested by quality assurance regulations after three months of storage.', 'APTT and PT show an increase from baseline to one month then remain constant up to three months, while, Fibrinogen, Factor II, Factor V, Factor VII, Factor X, Von Willbrand Factor, Protein C and Antithrombin decreased from baseline up to three months and then Factor VIII, Factor IX, Factor XI, Factor XII and Protein S, remained constant from baseline up to one month and decreased up to three months.",
            "output": [
                "Do cOAGULATION FACTORS LEVEL IN FRESH FROZEN PLASMA IN RWANDA?"
            ]
        },
        {
            "id": "task847-8ea7b19fa1384bfcb61df4cf9f21ba6c",
            "input": "We investigated the miR-196a2T>C rs11614913 variant in the initiation and progression of hepatocellular carcinoma (HCC).', 'A case-control research model was conducted and the genotypes of 109 HCC patients and 105 healthy controls were identified by direct sequencing. The correlation between the rs11614913 genotypes and the susceptibility to HCC was evaluated using an unconditional logistic regression model.', 'We found that 20/109 (18.3%) patients were TT homozygote, whereas 64/109 (58.8%) patients had the CT genotype, and 25/109 (22.9%) patients had the CC genotype. In control samples, the frequency of the TT homozygote was 33.3%, that of CT was 49.5%, and that of CC was 17.1%. After adjusting for age and gender by logistic regression analysis, we found significant differences in susceptibility to HCC by genotype (TT vs. CT+CC: OR\\u2009=\\u20092.52, 95%CI\\u2009=\\u20091.18-4.19; p\\u2009<\\u20090.05). The CT and CC genotypes were more common in HCC patients compared to controls. Moreover, the CT+CC genotypes were associated with a poor HCC prognosis.",
            "output": [
                "Does a Single-Nucleotide Polymorphism of miR-196a2T > C rs11614913 be Associated with Hepatocellular Carcinoma in the Chinese Population?"
            ]
        },
        {
            "id": "task847-47f9788f378b4d64bf19cfb52eab665d",
            "input": "Tissue expansion is a time-tested and frequently used procedure for utilizing local tissue to replace large defects. We aimed to assess the success & complications of tissue expansion in correction of post burn scalp alopecia.', 'In this study, 30 patients of scalp burn alopecia of 5 to 35 years age group were treated with tissue expansion of the scalp at Bahawal-Victoria Hospital from January 2013 to December 2014. The area of the scalp loss was within 1/5 to 2/5. Our technique employed an insertion site distal to the area needed to be expanded, attempting to minimize complication like extrusion & wound dehiscence. The patients were followed-up weekly during first month and then fortnightly for next four months.', 'Our study involved 8 male (26.67%) and 22 female subjects (73.33%) with a mean age of 21years. Flame burn accounted for the mostly 53.3% (n=16) of scalp burns & parieto-temporal region was most commonly affected in 33.4% (n=10) of subjects. Desired aesthetic results were achieved in all the patients without any major complication. Minor complication included mild infection in 8 (26.67%), seroma in 4 (13.33%) & wound dehiscence in 2 (6.67%) patients.",
            "output": [
                "Do reconstruction of post burn scalp alopecia by using expanded hair-bearing scalp flaps?"
            ]
        },
        {
            "id": "task847-cdd846abed1443cfb37dab1353c3665b",
            "input": "Given the role of microRNA in colorectal cancer (CRC) progression, we explored the association between microRNA (miRNA) expression and CRC-related prognosis.', 'Three types of tissue samples (primary CRC lesions without liver metastasis, primary lesions with liver metastasis, and liver metastatic tissues) were used for miRNA profiling to identify differentially expressed miRNA. Quantitative real-time PCR was used to examine miRNA expression in CRC cells and in tumor tissues.', 'MiR-132 was significantly down-regulated in primary CRC tissues with liver metastasis and liver metastatic lesions compared to primary lesions without liver metastasis. Multivariate analysis for overall survival indicated that low miR-132 expression was an independent prognostic factor for CRC patients (overall survival P\\xa0=\\xa00.040, disease-free survival P\\xa0=\\xa00.015). Ectopic expression of miR-132 significantly inhibited cell proliferation and cell invasion. The luciferase reporter assay revealed that anoctamin 1 (ANO1) was a direct target of miR-132. Kaplan-Meier survival curves showed that high ANO1 expression was a significant prognostic factor for overall survival of patients with CRC (P\\xa0=\\xa00.0344).",
            "output": [
                "Is down-Regulation of microRNA-132 Associated with Poor Prognosis of Colorectal Cancer?"
            ]
        },
        {
            "id": "task847-4b4e622dc29448a2889c5bc928ffaca6",
            "input": "It is uncertain whether neck circumference can be a risk indicator for subclinical atherosclerosis. We aimed to investigate their relationships measured by coronary artery calcium (CAC) and common carotid intima-media thickness (cc-IMT) with neck circumference in ELSA-Brasil.', 'In cross-sectional and sex-specific analyses of 2266 women (50.6 \u00b1 8.4 yrs) and 1886 men (50.7 \u00b1 9.0 yrs) with both cc-IMT and CAC, free from previous cardiovascular disease at baseline, we built logistic models using diverse cut-off points for CAC score (0 vs > 0, < 100 vs \u2265 100, < 400 vs \u2265 400 Agatston units) and cc-IMT (< 75 th percentile vs \u2265 75 th; <90th percentile vs \u2265 90 th) as dependent variables, after which adjustments for age and traditional cardiovascular risk factors were made. Mean neck circumference was 33.6 (\u00b1 2.4 cm) for women and 38.8 (\u00b1 2.6 cm) for men. In fully adjusted models including sociodemographic, cardiovascular risk factors and body-mass index and waist circumference, for each 1 standard deviation increase in neck circumference we found an odds ratio (OR, 95% CI) for IMT above the 75th percentile of (1.52, 1.16; 1.99) for women and (1.66, 1.28; 2.14) for men, and above the 90th cc-IMT percentile [1.66 (1.19; 2.32) for men but not for women [1.21 (0.80; 1.82)]. We found no association between neck circumference and CAC using different cut-off points (p > 0.05 for all).",
            "output": [
                "Is neck circumference associated with carotid intimal-media thickness but not with coronary artery calcium : Results from The ELSA-Brasil?"
            ]
        },
        {
            "id": "task847-8d60e8793ee34c81b7169e1d7e1ec088",
            "input": "Pediatric patients with high-risk neuroblastoma (HR NB) often fail to respond to upfront intensive multimodal therapy. Tumor-acquired suppression of apoptosis contributes to therapy resistance. Many HR NB tumors depend on the anti-apoptotic protein Bcl-2 for survival, through Bcl-2 sequestration and inhibition of the pro-apoptotic protein, Bim. Bcl-2 dependent xenografts derived from aggressive human NB tumors are cured with a combination of cyclophosphamide and ABT-737, a Bcl-2/Bcl-XL/Bcl-w small molecule antagonist. The oral analogue to ABT-737, Navitoclax (ABT-263), clinically causes an immediate drop in peripheral platelet counts as mature platelets depend on Bcl-xL for survival. This led to the creation of a Bcl-2 selective inhibitor, ABT-199 (Venetoclax). A Phase I trial of ABT-199 in CLL showed remarkable antitumor activity and stable patient platelet counts. Given Bcl-XL does not play a role in HR NB survival, we hypothesized that ABT-199 would be equally potent against HR NB.', 'Cytotoxicity and apoptosis were measured in human derived NB cell lines exposed to ABT-199 combinations. Co-Immunoprecipitation evaluated Bim displacement from Bcl-2, following ABT-199. Murine xenografts of NB cell lines were grown and then exposed to a 14-day course of ABT-199 alone and with cyclophosphamide.', 'Bcl-2 dependent NB cell lines are exquisitely sensitive to ABT-199 (IC50 1.5-5 nM) in vitro, where Mcl-1 dependent NBs are completely resistant. Treatment with ABT-199 displaces Bim from Bcl-2 in NB to activate caspase 3, confirming the restoration of mitochondrial apoptosis. Murine xenografts of Mcl-1 and Bcl-2 dependent NBs were treated with a two-week course of ABT-199, cyclophosphamide, or ABT-199/cyclophosphamide combination. Mcl-1 dependent tumors did not respond to ABT-199 alone and showed no significant difference in time to tumor progression between chemotherapy alone or ABT-199/cyclophosphamide combination. In contrast, Bcl-2 dependent xenografts responded to ABT-199 alone and had sustained complete remission (CR) to the ABT-199/cyclophosphamide combination, with one recurrent tumor maintaining Bcl-2 dependence and obtaining a second CR after a second course of therapy.",
            "output": [
                "Does select Bcl-2 antagonism restore chemotherapy sensitivity in high-risk neuroblastoma?"
            ]
        },
        {
            "id": "task847-87768a1f5b224c54aacc68546af6bb84",
            "input": "Direct hemoperfusion with a polymyxin B-immobilized column (PMX-DHP) adsorbs endotoxin and has been used for the treatment of septic shock. Yet, the mechanisms by which PMX-DHP acts on acute kidney injury are only partially understood.', 'Rats were anesthetized, tracheostomized, and placed on mechanical ventilation. The animals were randomized to three groups: a cecal ligation and puncture (CLP) + dummy-DHP group (n = 10), a CLP + PMX-DHP group (n = 10), and a sham group (n = 4). Four hours after CLP, a dummy-DHP or PMX-DHP was performed for 1 h. The heart rate, mean arterial pressure, arterial blood gases, and plasma concentrations of creatinine, lactate, potassium, interleukin (IL)-6, and IL-10 were measured at 0 h and 8 h. Eight hours after CLP, the kidney was harvested, and histopathologic examination was performed. The expressions of cleaved poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-\u03baB p65 were examined by immunohistochemistry. A terminal deoxynucleotide transferase dUTP nick-end labeling assay was performed to detect apoptotic nuclei in kidney sections.', 'PMX-DHP maintained hemodynamics and the acid-base balance and significantly (P < 0.05) decreased the plasma concentrations of lactate, creatinine, potassium, IL-6, and IL-10 compared with dummy-DHP. PMX-DHP significantly (P < 0.001) attenuated the expressions of cleaved PARP and NF-\u03baB p65 in renal tubular cells and renal tubular cell apoptosis compared with dummy-DHP.",
            "output": [
                "Does polymyxin B hemoperfusion prevent acute kidney injury in sepsis model?"
            ]
        },
        {
            "id": "task847-a3c16399e2574b1c96ecd816ce4456ca",
            "input": "Sildenafil is a phosphodiesterase inhibitor used clinically for treating erectile dysfunction. Few studies suggest sildenafil to be a renoprotective agent. The present study investigated the involvement of peroxisome proliferator-activated receptor \u03b3 (PPAR-\u03b3) in sildenafil-mediated protection against ischemia-reperfusion-induced acute kidney injury (AKI) in rats.', 'The rats were subjected to ischemia-reperfusion injury (IRI) with 40 min of bilateral renal ischemia followed by reperfusion for 24 h. The renal damage was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, electrolytes, and microproteinuria in rats. The thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. The hematoxylin-eosin staining was carried out to demonstrate histopathologic changes in renal tissues. Sildenafil (0.5 and 1.0 mg/kg, intraperitoneal) was administered 1 h before subjecting the rats to renal IRI. In a separate group, bisphenol A diglycidyl ether (30 mg/kg, intraperitoneal), a PPAR-\u03b3 receptor antagonist, was given before sildenafil administration followed by IRI.', 'The ischemia-reperfusion demonstrated marked AKI with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. The administration of sildenafil demonstrated significant protection against ischemia-reperfusion-induced AKI. The prior treatment with bisphenol A diglycidyl ether abolished sildenafil-mediated renal protection, thereby confirming involvement of PPAR-\u03b3 agonism in the sildenafil-mediated renoprotective effect.",
            "output": [
                "Does sildenafil obviate ischemia-reperfusion injury-induced acute kidney injury through peroxisome proliferator-activated receptor \u03b3 agonism in rats?"
            ]
        },
        {
            "id": "task847-b0c11b1cb20b472c96cb2607d3a0a00f",
            "input": "Cardiac surgery produces a proinflammatory response characterized by cytokine production. Proinflammatory cytokines such as interleukin 6 (IL-6) may contribute to morbidity and mortality after cardiopulmonary bypass (CPB). Elderly patients undergoing CPB are at increased risk of morbidity and mortality. We hypothesized that patients aged >70 y produce more IL-6 during CPB.', 'Twenty-three patients (ages 23-80) undergoing cardiac surgery had blood sampled from the ascending aorta and coronary sinus on initial cannulation for bypass, at 30 min of aortic cross-clamp time, on release of the aortic cross-clamp, and at 20 min after reperfusion. Group 1 patients (n = 8) were aged <60 y, group 2 patients (n = 7) were aged between 60 and 70 y, and group 3 patients (n = 8) were aged >70 y. Plasma levels of tumor necrosis factor-alpha, IL-1, and IL-6 were analyzed.', 'The three groups did not differ with respect to preoperative ejection fraction, New York Heart Association classification, mean aortic cross-clamp time, or mean CPB time. IL-6 levels rose throughout myocardial ischemia and reperfusion in all three age groups. The increase in IL-6 during ischemia and reperfusion in the age group >70 was greater than the increase in younger patients. IL-6 was similar in the coronary sinus and the ascending aorta.",
            "output": [
                "Does interleukin 6 production during cardiac surgery correlate with increasing age?"
            ]
        },
        {
            "id": "task847-5ad9cd57edfb4298b8b476f45d01770d",
            "input": "Currently, no serological prognostic marker exists for pancreatic neuroendocrine tumors (pNETs). Previous studies have suggested potential for chromogranin A (CgA); however, the prognostic capability of CgA remains controversial. Our purpose was to explore preoperative CgA levels in predicting outcomes in patients with resected pNETs.', 'Patients with preoperative CgA levels who underwent resection of a pancreatic neuroendocrine tumor between July 2002 and May 2013 were identified from a prospective database. An elevated preoperative CgA was defined as a CgA laboratory value above the normal limit of the assay. All patients had pathologically confirmed primary pancreatic tumors. Outcomes were compared between elevated and normal CgA groups.', 'A total of 38 patients were identified that met inclusion criteria. Of these, 45% were male, and the median age was 57 y (range, 17-81 y). All underwent resection with curative intent. Elevated preoperative CgA was present in 16 patients (42%). There were no differences in node positivity or margin status between the normal CgA and elevated CgA groups on univariate analysis. However, tumor size and grade were significantly different between the two groups. Both disease-free survival (DFS; P = 0.006) and overall survival (P = 0.017) were negatively impacted by an elevated preoperative CgA (median follow-up; 40 mo).",
            "output": [
                "Does chromogranin A predict survival for resected pancreatic neuroendocrine tumors?"
            ]
        },
        {
            "id": "task847-f00574111078463f97a3e5c882b994fa",
            "input": "Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans.', \"Anthropometrics, glucose, insulin, C-peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C-peptide. Correlations were calculated using the Spearman correlation coefficient (\u03c1). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis.\", 'Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P\\u2009<\\u20090.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P\\u2009<\\u20090.05). Moreover, C-peptide (AUC\\u2009=\\u20090.72-0.78) was a better marker than insulin (AUC\\u2009=\\u20090.62-0.72) for MetS (P\\u2009<\\u20090.05). Finally, HOMA2-IR calculated with C-peptide (AUC\\u2009=\\u20090.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC\\u2009=\\u20090.68-0.75, P\\u2009<\\u20090.05) at determining MetS.",
            "output": [
                "Does c-Peptide be a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico?"
            ]
        },
        {
            "id": "task847-14c489e46a8849d7b41ed0b5a3bbafcd",
            "input": "To examine the relationship between and impact of spontaneous bacteria peritonitis (SBP) and renal failure requiring dialysis in waitlisted liver transplant (LT) candidates.', 'Renal failure is a common and severe complication in cirrhotic patients with SBP. Approximately one-third of patients with SBP develop renal failure despite treatment of infection. However, the incidence of renal failure requiring dialysis in LT waitlisted patients who have developed SBP is unknown. The high mortality observed in this group has also raised debate about resource utilization in the care of these patients.', 'Data from the United Network for Organ Sharing Standard Transplant and Research files were collected retrospectively between 1994 and 2012. The primary endpoint measured was first time initiation of dialysis while on the LT wait list. Secondary endpoints included waitlist time and mortality on wait list.', 'A total of 42,085 patients were included. SBP at time of listing was diagnosed in 2,352 patients (5.6%) and first time initiation of dialysis while on the wait list occurred in 2,367 patients (6.2%). Unadjusted OR for requiring dialysis for patients listed with SBP was 1.66 (p < 0.001). When controlled for age, gender, BMI, diabetes mellitus, baseline creatinine, MELD score, serum albumin at listing, the adjusted OR for dialysis was 1.24 (p = 0.007) in waitlisted patients with SBP. Patients with SBP at time of listing had a mean waitlist time 142.1 d vs. 198.7 d in non-SBP patients (p < 0.001).",
            "output": [
                "Is spontaneous bacterial peritonitis a risk factor for renal failure requiring dialysis in waitlisted liver transplant candidates?"
            ]
        },
        {
            "id": "task847-261b42d478e24f58bab4127c7f34ca19",
            "input": "The objective of this study was to test the hypothesis that ovarian kisspeptin (kiss1) and its receptor (kiss1r) expression are affected by age, obesity, and the age- and obesity-related chemokine monocyte chemoattractant protein-1 (MCP-1).', 'Ovaries from reproductive-aged and older C57BL/6J mice fed normal chow (NC) or high-fat (HF) diet, ovaries from age-matched young MCP-1 knockout and young control mice on NC, and finally, cumulus and mural granulosa cells (GCs) from women who underwent in vitro fertilization (IVF) were collected. Kiss1, kiss1r, anti-Mullerian hormone (AMH), and AMH receptor (AMHR-II) messenger RNA (mRNA) expression levels were quantified using real-time polymerase chain reaction (RT-PCR).', 'In mouse ovaries, kiss1 and kiss1r mRNA levels were significantly higher in old compared to reproductive-aged mice, and diet-induced obesity did not alter kiss1 or kiss1r mRNA levels. Compared to young control mice, young MCP-1 knockout mice had significantly lower ovarian kiss1 mRNA but significantly higher AMH and AMHR-II mRNA levels. In human cumulus GCs, kiss1r mRNA levels were positively correlated with age but not with BMI. There was no expression of kiss1 mRNA in either cumulus or mural GCs.",
            "output": [
                "Is ovarian kisspeptin expression related to age and to monocyte chemoattractant protein-1?"
            ]
        },
        {
            "id": "task847-e311988183bc4d9f9bb99f0bdecc6e55",
            "input": "Muscle density is a risk factor for fractures in older adults; however, its association with falls is not well described. After adjusting for biologically relevant confounding factors, a unit decrease in muscle density was associated with a 17\\xa0% increase in odds of reporting a fall, independent of functional mobility.', 'Falls are the leading cause of injury, disability, and fractures in older adults. Low muscle density (i.e., caused by muscle adiposity) and functional mobility have been identified as risk factors for incident disability and fractures in older adults; however, it is not known if these are also independently associated with falls. The purpose of this study was to explore the associations of muscle density and functional mobility with fall status.', 'Cross-sectional observational study of 183 men and women aged 60-98\\xa0years. Descriptive data, including a 12-month fall recall, Timed Up and Go (TUG) test performance, lower leg muscle area, and density. Odds ratio (OR) of being a faller were calculated, adjusted for age, sex, body mass index, general health status, diabetes, and comorbidities.', 'Every mg/cm(3) increase in muscle density (mean 70.2, SD 2.6\\xa0mg/cm(3)) independently reduced the odds of being a faller by 19\\xa0% (OR 0.81 [95\\xa0% CI 0.67 to 0.97]), and every 1\\xa0s longer TUG test time (mean 9.8, SD 2.6\\xa0s) independently increased the odds by 17\\xa0% (OR 1.17 [95\\xa0% CI 1.01 to 1.37]). When both muscle density and TUG test time were included in the same model, only age (OR 0.93 [95\\xa0% CI 0.87 to 0.99]) and muscle density (OR 0.83 [95\\xa0% CI 0.69 to 0.99]) were independently associated with fall status.",
            "output": [
                "Is lower leg muscle density independently associated with fall status in community-dwelling older adults?"
            ]
        },
        {
            "id": "task847-f9d7ee3d1ff4465c9043a723f4273ff2",
            "input": "To determine the reliability of Internet-based information on community-based weight-loss programs and grade their degree of concordance with 2013 American Heart Association, American College of Cardiology, and The Obesity Society weight-management guidelines.', 'An online search was conducted for weight-loss programs in the Maryland-Washington, DC-Virginia corridor. Content analysis was performed to abstract program components from their websites, and then 80 programs were randomly selected for a telephone survey to verify this information. Reliability of Internet information was determined in comparison with telephone interview responses.', 'Of the 191 programs, 1% were graded as high, 8% as moderate, and 91% as low with respect to guideline concordance based on website content. Fifty-two programs participated in the telephone survey (65% response rate). Program intensity, diet, physical activity, and use of behavioral strategies were underreported on websites as compared to description of these activities during the phone interview. Within the subsample, 6% of programs were graded as high based on website information, whereas 19% were graded as high after the telephone interview.",
            "output": [
                "Are guideline-concordant weight-loss programs in an urban area uncommon and difficult to identify through the internet?"
            ]
        },
        {
            "id": "task847-c4bb31479b2d42ecbc3e51f6a77826e7",
            "input": "Video capsule endoscopy (VCE) is limited by incomplete procedures. There are also contraindications to the standard ingestion of the capsule that require endoscopic placement. Our aim was to compare the study completion rate of VCE after oral ingestion and endoscopic deployment.', 'We performed a review of all VCE from April 2010 through March 2013. Inpatient and outpatient cohorts grouped by the method of capsule delivery were formed and compared. Multivariable logistic regression modeling was utilized adjusting for variables with a P\\xa0value \u2264\\u200a0.1 in group comparisons. Log-rank analysis was used to compare transit times.', 'A total of 687 VCE were performed, including 316 inpatient (36 endoscopic deployment, 280 oral ingestion) and 371 outpatient (20 endoscopic deployment, 351 oral ingestion). For VCE on hospitalized patients, the completion rates were similar after endoscopic deployment and oral ingestion (72\\u200a% vs 73\\u200a%, P\\u200a=\\u200a0.94). The completion rates were also similar for ambulatory patients (90\\u200a% vs 87\\u200a%, P\\u200a=\\u200a0.69). There remained no difference after multivariable modeling for inpatients (P\\u200a=\\u200a0.71) and outpatients (P\\u200a=\\u200a0.46). Total transit times were not significantly different.",
            "output": [
                "Are video capsule endoscopy completion and total transit times similar with oral or endoscopic delivery?"
            ]
        },
        {
            "id": "task847-65a0ae03be7b4f4dbc9603b66665e0f4",
            "input": "We aimed to identify whether ST-segment abnormalities, in the admission or during in-hospital stay, are associated with survival and/or new incident myocardial infarction (MI) in 623 non-ST-elevation acute coronary syndrome participants of the Strategy of Registry of Acute Coronary Syndrome (ERICO) study.', 'ERICO is conducted in a community-based hospital. ST-segment analysis was based on the Minnesota Code. We built Cox regression models to study whether ECG was an independent predictor for clinical outcomes.', 'Median follow-up was 3years. We found higher risk of death due to MI in individuals with ST-segment abnormalities in the final ECG (adjusted hazard ratio: 2.68; 95% confidence interval: 1.14-6.28). Individuals with ST-segment abnormalities in any tracing had a non-significant trend toward a higher risk of fatal or new non-fatal MI (p=0.088).",
            "output": [
                "Are sT-segment abnormalities associated with long-term prognosis in non-ST-segment elevation acute coronary syndromes : The ERICO-ECG study?"
            ]
        },
        {
            "id": "task847-92ad495be3de4eb4af5606ac97a32189",
            "input": "Lung morphogenesis is regulated by interactions between the canonical Wnt/\u03b2-catenin and Kras/ERK/Foxm1 signaling pathways that establish proximal-peripheral patterning of lung tubules. How these interactions influence the development of respiratory epithelial progenitors to acquire airway as compared to alveolar epithelial cell fate is unknown. During branching morphogenesis, SOX9 transcription factor is normally restricted from conducting airway epithelial cells and is highly expressed in peripheral, acinar progenitor cells that serve as precursors of alveolar type 2 (AT2) and AT1 cells as the lung matures.', 'To identify signaling pathways that determine proximal-peripheral cell fate decisions, we used the SFTPC gene promoter to delete or overexpress key members of Wnt/\u03b2-catenin and Kras/ERK/Foxm1 pathways in fetal respiratory epithelial progenitor cells. Activation of \u03b2-catenin enhanced SOX9 expression in peripheral epithelial progenitors, whereas deletion of \u03b2-catenin inhibited SOX9. Surprisingly, deletion of \u03b2-catenin caused accumulation of atypical SOX9-positive basal cells in conducting airways. Inhibition of Wnt/\u03b2-catenin signaling by Kras(G12D) or its downstream target Foxm1 stimulated SOX9 expression in basal cells. Genetic inactivation of Foxm1 from Kras(G12D) -expressing epithelial cells prevented the accumulation of SOX9-positive basal cells in developing airways.",
            "output": [
                "Are \u03b2-catenin and Kras/Foxm1 signaling pathway critical to restrict Sox9 in basal cells during pulmonary branching morphogenesis?"
            ]
        },
        {
            "id": "task847-c860840d87e842918bebe941544e11e5",
            "input": "Foraminal stenosis is a common cause of cervical radiculopathy. Posterior cervical cages can indirectly increase foraminal area and decompress the nerve root. The aim of this study was to assess the influence of bilateral posterior cervical cages on the surface area and shape of the neural foramen.', 'Radiographic analysis was performed on 43 subjects enrolled in a prospective, multi-center study. CT scans were obtained at baseline and 6- and 12-months after cervical fusion using bilateral posterior cervical cages. The following measurements were performed on CT scan: foraminal area (A), theoretical area (TA), height (H), superior diagonal (DSI), inferior diagonal (DIS), and inferior diagonal without implant (DISI). Comparisons were performed using R-ANOVA with a significance of \u03b1\\xa0<\\xa00.05.', 'Foraminal area, height, TA and DISI were significantly greater following placement of the implant. The mean (SD) A increased from 4.01 (1.09) mm(2) before surgery to 4.24 (1.00) mm(2) at 6\\xa0months, and 4.18 (1.05) mm(2) at 12\\xa0months after surgery (p\\xa0<\\xa00.0001). Foraminal height (H) increased from mean (SD) 9.20 (1.08) mm at baseline to 9.65 (1.06) mm and 9.55 (1.14) mm at 6- and 12-months post-operatively, respectively (p\\xa0<\\xa00.0001). The mean DIS did not change significantly. There was a significant decrease in DSI: 6.18 (1.59) mm pre-operatively, 5.95 (1.47) mm and 5.73 (1.46) mm at 6- and 12-months (p\\xa0<\\xa00.0001).",
            "output": [
                "Do cervical cages placed bilaterally in the facet joints from a posterior approach significantly increase foraminal area?"
            ]
        },
        {
            "id": "task847-8b5d0306f58d4edfb36fd4cd11956bad",
            "input": "To explore the perceived needs, obstacles to services, psychological distress and social problem-solving abilities of family members of persons with ABI at a post-acute community-based brain injury rehabilitation facility and offer suggestions for methods of assessment and providing support.', 'Twenty-nine family members who did not provide daily care, but were involved in the care process.', 'Participants completed self-report questionnaires including the FNQ:R, SOS, DASS-21, WHO-QOL BREF and SPSI:R-S.', 'Participants reported informational and professional needs as most met and involvement in care, instrumental support and emotional support as most unmet. Most were satisfied with the amount of professional help and services and had confidence in the quality of care. Nearly half of the family members felt there were few ABI-related resources in the community and one third were unaware of good ABI treatment resources in their community. Psychosocial functioning was generally average.",
            "output": [
                "Does family need at a post-acute rehabilitation setting and suggestions for supports?"
            ]
        },
        {
            "id": "task847-fb5f41ed9f0e4bfdbcb01e94117133e7",
            "input": "To explore the implication of serial coronary changes on the late coronary outcomes in patients with Kawasaki disease (KD) with coronary aneurysms \u2267 4 mm.', 'We performed a retrospective review of 78 patients with KD with large coronary aneurysms (1980-2013, male: 76.9%; 792 patient-years). Progressive coronary dilatation was defined for those with progressive enlargement of coronary arteries in 3 consecutive echocardiograms.', 'We studied 27 patients with KD with giant aneurysms (\u2267 8 mm) and 51 patients with KD with medium aneurysms (4-8 mm). All the giant and 43.1% of medium aneurysms persisted during the study period. For the patients with giant aneurysms, their 10-year freedom from acute myocardial infarction/cardiovascular death and all ischemia was 66% and 52%, respectively. The median intervals for the aneurysm diameters reaching their peak were 3.3 months (giant) and 0.25 months (medium), respectively. In patients with giant aneurysms, the 10-year freedom from ischemia was much lower in those with progressive coronary dilatation (28% vs 59%, P = .021). In patients with medium aneurysms, the probability of 5-year persistence of aneurysm was much greater (67.2% vs 14.8%, P < 10(-3)) in those with progressive coronary dilatation. Male sex and intravenous immunoglobulin therapy were not associated with the late outcomes in the patients with KD who had aneurysms larger than 4 mm.",
            "output": [
                "Does progressive Coronary Dilatation predict Worse Outcome in Kawasaki Disease?"
            ]
        },
        {
            "id": "task847-f98da2e6c77e4ce580a0e6bbd8e9a6fa",
            "input": "Multiple population-based studies have suggested increasing omission of radiation therapy in favor of alternative treatment strategies in lymphomas, with an associated negative impact on survival. Radiation therapy has long been considered the standard management for many mucosa-associated lymphoid tissue lymphomas. Thus, we aimed to evaluate patterns of treatment utilization and survival.', 'A retrospective analysis based on the National Cancer Database was performed on 22,378 patients with splenic, nodal, or extranodal stage I-II marginal zone lymphoma diagnosed between 1998 and 2012. A logistic regression model was used to assess the association between sociodemographic, tumor, and treatment characteristics and the utilization of radiation therapy. Multivariate propensity score-adjusted Cox proportional hazards models were performed to identify factors independently associated with overall survival (OS).', 'Of 22,378 patients, 82% had stage I disease, 77% had extranodal mucosa-associated lymphoid tissue lymphoma, 5% had splenic marginal zone lymphoma, and 64% were older than 60 years. Radiation therapy utilization decreased from a peak of 39% in 2007 to 33% in 2011 (P < .001), with a corresponding significant increase in systemic therapy utilization. Radiation therapy was associated with a 5- and 10-year OS of 86.7% and 68.8% compared with 78.3% and 54.3% for no radiation therapy (P < .001). On multivariate propensity score-adjusted survival analysis, radiation therapy remained independently associated with improved OS (hazard of death, 0.75; 95% confidence interval, 0.65-0.85; P < .001).",
            "output": [
                "Does underutilization of radiation therapy in early-stage marginal zone lymphoma negatively impact overall survival?"
            ]
        },
        {
            "id": "task847-bfaff8996a094a8cbe90043e3d5a1a7d",
            "input": "Intrauterine growth restriction (IUGR) results from either maternal undernutrition or impaired placental blood flow, exposing offspring to increased perinatal mortality and a higher risk of metabolic syndrome and cardiovascular disease during adulthood. l-Citrulline is a precursor of l-arginine and nitric oxide (NO), which regulates placental blood flow. Moreover, l-citrulline stimulates protein synthesis in other models of undernutrition.', 'The aim of the study was to determine whether l-citrulline supplementation would enhance fetal growth in a model of IUGR induced by maternal dietary protein restriction.', 'Pregnant rats were fed either a control (20% protein) or a low-protein (LP; 4% protein) diet. LP dams were randomly allocated to drink tap water either as such or supplemented with l-citrulline (2 g \u00b7 kg(-1) \u00b7 d(-1)), an isonitrogenous amount of l-arginine, or nonessential l-amino acids (NEAAs). On day 21 of gestation, dams received a 2-h infusion of l-[1-(13)C]-valine until fetuses were extracted by cesarean delivery. Isotope enrichments were measured in free amino acids and fetal muscle, liver, and placenta protein by GC-mass spectrometry.', 'Fetal weight was \u223c29% lower in the LP group (3.82 \u00b1 0.06 g) than in the control group (5.41 \u00b1 0.10 g) (P < 0.001). Regardless of supplementation, fetal weight remained below that of control fetuses. Yet, compared with the LP group, l-citrulline and l-arginine equally increased fetal weight to 4.15 \u00b1 0.08 g (P < 0.05) and 4.13 \u00b1 0.1 g (P < 0.05 compared with LP), respectively, whereas NEAA did not (4.05 \u00b1 0.05 g; P = 0.07). Fetal muscle protein fractional synthesis rate was 35% lower in the LP fetuses (41% \u00b1 11%/d) than in the control (61% \u00b1 13%/d) fetuses (P < 0.001) and was normalized by l-citrulline (56% \u00b1 4%/d; P < 0.05 compared with LP, NS compared with control) and not by other supplements. Urinary nitrite and nitrate excretion was lower in the LP group (6.4 \u00b1 0.8 \u03bcmol/d) than in the control group (17.9 \u00b1 1.1 \u03bcmol/d; P < 0.001) and increased in response to l-citrulline or l-arginine (12.1 \u00b1 2.2 and 10.6 \u00b1 0.9 \u03bcmol/d; P < 0.05), whereas they did not in the LP + NEAA group.",
            "output": [
                "Does l-Citrulline Supplementation enhance Fetal Growth and Protein Synthesis in Rats with Intrauterine Growth Restriction?"
            ]
        },
        {
            "id": "task847-c487bd31acdf44bb9ed2e475aabdd96e",
            "input": "The tight junctions (TJs) are essential for maintenance of the intestinal mucosal barrier integrity. Results of our recent work show that dietary l-glutamine (Gln) supplementation enhances the protein abundance of TJ proteins in the small intestine of piglets. However, the underlying mechanisms remain largely unknown.', 'This study was conducted to test the hypothesis that Gln regulates TJ integrity through calcium/calmodulin-dependent kinase 2 (CaMKK2)-AMP-activated protein kinase (AMPK) signaling which, in turn, contributes to improved intestinal mucosal barrier function.', 'Jejunal enterocytes isolated from a newborn pig were cultured in the presence of 0-2.0 mmol Gln/L for indicated time points. Cell proliferation, monolayer transepithelial electrical resistance (TEER), paracellular permeability, expression and distribution of TJ proteins, and phosphorylated AMPK were determined.', 'Compared with 0 mmol Gln/L, 2.0 mmol Gln/L enhanced (P < 0.05) cell growth (by 31.9% at 48 h and 11.1% at 60 h). Cells treated with 2 mmol Gln/L increased TEER by 32.2% at 60 h, and decreased (P < 0.05) TJ permeability by 20.3-40.0% at 36-60 h. In addition, 2.0 mmol Gln/L increased (P < 0.05) the abundance of transmembrane proteins, such as occludin, claudin-4, junction adhesion molecule (JAM)-A, and the plaque proteins zonula occludens (ZO)-1, ZO-2, and ZO-3 by 1.8-6 times. In contrast, 0.5 mmol Gln/L had a moderate effect on TJ protein abundance (20.2-70.5%; P < 0.05) of occludin, claudin-3, claudin-4, JAM-A, and ZO-1. 2.0 mmol Gln/L treatment led to a greater distribution of claudin-1, claudin-4, and ZO-1 at plasma membranes compared with 0 mmol Gln/L. This effect of Gln was mediated by the activation of CaMKK2-AMPK signaling, because either depletion of calcium from the medium or the presence of an inhibitor of CaMKK2 abrogated the effect of Gln on epithelial integrity.",
            "output": [
                "Does l-Glutamine enhance Tight Junction Integrity by Activating CaMK Kinase 2-AMP-Activated Protein Kinase Signaling in Intestinal Porcine Epithelial Cells?"
            ]
        },
        {
            "id": "task847-ab858d49847b427499d0a6349a43e44b",
            "input": "Patients with type 2 diabetes have an increased risk of atherosclerosis and vascular disease. Vitamin D deficiency is associated with vascular disease and is prevalent in diabetes patients. We undertook this study to determine the association between 25-hydroxyvitamin D (25[OH]D) levels and prevalence of peripheral arterial disease (PAD) in type 2 diabetes patients.', 'A total of 1028 type 2 diabetes patients were recruited at Nanjing Medical University Affiliated Nanjing Hospital from November 2011 to October 2013. PAD was defined as an ankle-brachial index (ABI)\\xa0<\\xa00.9. Cardiovascular risk factors (blood pressure, HbA1c, lipid profile), comorbidities, carotid intima-media thickness (IMT) and 25(OH)D were assessed.', 'Overall prevalence of PAD and of decreased 25(OH)D (<30\\xa0ng/mL) were 20.1% (207/1028) and 54.6% (561/1028), respectively. PAD prevalence was higher in participants with decreased (23.9%) than in those with normal (15.6%) 25(OH)D (\u226530\\xa0ng/mL, p\\xa0<0.01). Decreased 25(OH)D was associated with increased risk of PAD (odds ratio [OR], 1.69, 95% CI: 1.17-2.44, p\\xa0<0.001) and PAD was significantly more likely to occur in participants \u226565\\xa0years of age (OR, 2.56, 95% CI: 1.51 -4.48, vs. 1.21, 95% CI: 0.80-1.83, p-interaction\\xa0=\\xa00.027). After adjusting for known cardiovascular risk factors and potential confounding variables, the association of decreased 25(OH)D and PAD remained significant in patients <65\\xa0years of age (OR, 1.55; 95% CI: 1.14-2.12, p\\xa0=\\xa00.006).",
            "output": [
                "Does low 25-Hydroxyvitamin D Level be Associated with Peripheral Arterial Disease in Type 2 Diabetes Patients?"
            ]
        },
        {
            "id": "task847-22045b0056d647138e730f406224e992",
            "input": "We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors.', 'All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes -involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes- was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats.', 'After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1\u03b2 (IL1\u03b2), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024).",
            "output": [
                "Are interleukin-1\u03b2 gene variants associated with QTc interval prolongation following cardiac surgery : a prospective observational study?"
            ]
        },
        {
            "id": "task847-4951a3a44cbb43099450e87c9cb144d3",
            "input": "Extracellular vesicles (EVs), including circulating microvesicles (MVs) or mi- croparticles (MPs) and exosomes, derived from cells or platelets are present in the peripheral blood and are important elements involved in the activation of the coagulation system, transport of macromolecules and intercellular communication. In patients with vascular complications (including diabetes), the number of EVs is significantly increased during the acute phase of the disease. However, less is known about EVs release in the chronic state of diabetes.', 'To analyse the profile of inflammatory cytokines and angiogenic factors in EVs in diabetic patients with ocular and vascular complications.', 'The study included patients with diabetes and varying degrees of ocular complications including retinopathy (n = 48) and the control group (n = 13). EV-enriched and EV-depleted fractions were obtained from platelet-poor plasma by means of the centrifugation method (16 000 g, for 90 min). In screening, the profile of cytokines with pro-angiogenic effects was preliminary assessed using the protein microarray technology for controlled diabetic patients - CD, uncontrolled diabetic patients - UD and for the control group. In all patients, concentrations of cytokines: RANTES (Regulated on Activation, Normal T-cell Expressed and secreted) and Ang-2 (angiopoietin-2) were assayed using the ELISA method. Common blood and biochemical tests were performed.', 'In patients with diabetes, analysis of supernatant revealed significantly increased concentrations of basic fibroblast growth factor (bFGF) and soluble receptor for vascular endothelial growth factor 2 (V-EGFR2) when compared to the control group: 49 (10.5-122) vs. 24 (2-72.5) SD (p = 0.03) and 260 (195.5-351) vs. 360 (256-461.5) SD (p = 0.01). In UD patients, concentrations of RANTES, angiostatin, tumor necrosis factor-\u03b1 (TNF), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP1 and TIMP2) were relatively higher in the EV-enriched fraction when compared to the EV-depleted fraction. Post hoc analysis revealed significant differences between UC patients and the control group in RANTES (16.73 (14.41-18.93) vs. 14.62 (12.37-15.28) mg/ml; p = 0.0235) and Ang-2 (2.76 (2.23-4.64) ng/ml vs. 1.74 (1.54-1.93); p = 0.0316) concentrations. These analyses did not reveal any significant differences in RANTES and Ang-2 concentrations between CD patients and the control group.",
            "output": [
                "Do extracellular vesicles participate in the transport of cytokines and angiogenic factors in diabetic patients with ocular complications?"
            ]
        },
        {
            "id": "task847-a819547f69e24037b88eaae97ec6468e",
            "input": "OLT is the best alternative for patients with end-stage liver diseases. However, as the need for organs surpasses donor availability, alternatives to OLT are required. LCT could be a useful option versus OLT in several patients even though its low cell-engraftment hampers its efficiency. Endothelial cell barrier is the main obstacle for the implantation of cells into the parenchyma. Our study has focused on the modification of the endothelial barrier with monoclonal antibodies against adhesion molecules in order to increase cell engraftment in a mouse model of liver cell transplantation.', 'Anti-mouse CD54 and anti-mouse CD61 antibodies were administered intrasplenically to healthy mice within 60 min prior to stem cell transplantation. Animals were sacrificed either short term at 2h or middle term seven days after transplantation. Immunohistochemical techniques to detect alkaline phosphatase activity were used to identify the transplanted cells within the liver parenchyma.', 'Anti-CD54 and anti-CD61 administration increases vascular patency and cell engraftment. This represents a 32% and 45% increase, respectively, of engrafted cells compared to the control (p<0.05).",
            "output": [
                "Does blockade of cell adhesion molecules enhance cell engraftment in a murine model of liver cell transplantation?"
            ]
        },
        {
            "id": "task847-10e2f152531743c6b0574545fa6a8c4e",
            "input": "Paracrine signalling mediated by cytokine secretion is essential for liver regeneration after hepatic resection, yet the mechanisms of cellular crosstalk between immune and parenchymal cells are still elusive. Interleukin-22 (IL-22) is released by immune cells and mediates strong hepatoprotective functions. However, it remains unclear whether IL-22 is critical for the crosstalk between liver lymphocytes and parenchymal cells during liver regeneration after partial hepatectomy (PH). Here, we found that plasma levels of IL-22 and its upstream cytokine, IL-23, are highly elevated in patients after major liver resection. In a mouse model of PH, deletion of IL-22 was associated with significantly delayed hepatocellular proliferation and an increase of hepatocellular injury and endoplasmic reticulum stress. Using Rag1(-/-) and Rag2(-/-) \u03b3c(-/) (-) mice, we show that the main producers of IL-22 post-PH are conventional natural killer cells and innate lymphoid cells type 1. Extracellular adenosine triphosphate (ATP), a potent danger molecule, is elevated in patients immediately after major liver resection. Antagonism of the P2-type nucleotide receptors, P2X1 and P2Y6, significantly decreased IL-22 secretion ex vivo. In vivo, specific inhibition of P2X1 was associated with decreased IL-22 secretion, elevated liver injury, and impaired liver regeneration.",
            "output": [
                "Is p2X1-regulated IL-22 secretion by innate lymphoid cells required for efficient liver regeneration?"
            ]
        },
        {
            "id": "task847-e50ee66df6134d6a803d20f2e72b8fdb",
            "input": "To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later.', 'Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24\\u2009hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later.', 'A university hospital acute stroke unit.', 'Thirty-four mild ischemic stroke patients.', 'None.', 'One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework.', 'The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels (p\\u2009=\\u20090.041) and increases in activities of daily living (p\\u2009=\\u20090.011). Material support from friends and family was associated with increases in activities of daily living (p\\u2009=\\u20090.012). No effect was observed for support received from medical staff.",
            "output": [
                "Is very early social support following mild stroke associated with emotional and behavioral outcomes three months later?"
            ]
        },
        {
            "id": "task847-5c91ac8db6b14eb0a0c708f7bca3d38a",
            "input": "Until recently, nutritional guidelines did not support early introduction of allergenic foods into the diet of high-risk infants. Following recent studies, this approach is beginning to change, at least for peanuts. This review will examine the change in nutritional guidelines and the scientific data that led to these changes.', \"In a recent prospective controlled study, regular consumption of peanut protein in infants from 4-11 months of age with atopic dermatitis or egg allergy, was associated with lower prevalence of peanut allergy (1.9%) at 60 months of age compared with peanut avoidance (13.7%). Other studies demonstrated that earlier introduction of cow's milk protein and egg powder were also associated with decreased risk for milk and egg allergy, respectively.",
            "output": [
                "Is timing of allergen exposure and the development of food allergy : treating before the horse out of the barn?"
            ]
        },
        {
            "id": "task847-65e1ce635d3f4772ade419b14788be09",
            "input": "To explore the effectiveness of bone transportation by ring type extenal fixator combined with locked intramedullary nail for tibial non-infectious defect.', 'Between June 2008 and October 2012, 22 cases of tibial large segment defect were treated. There were 15 males and 7 females, aged 24-58 years (mean, 36.8 years), including 17 cases of postoperative nonunion or malunion healing, and 5 cases of large defect. After debridement, bone defect size was 5.0-12.5 cm (mean, 8.05 cm). Bone transportation was performed by ring type external fixator combined with locked intramedullary nail, the mean indwelling duration of external fixation was 10.2 months (range, 2-26 months); the external fixation index was 1.57 months/cm (range, 0.3-3.2 months/cm); and the mean length increase was 8.05 cm (range, 5.0-12.5 cm).', 'All patients were followed up 19-58 months (mean, 32 months). No infection occurred after operation and all patients obtained bony union, and the union time was 4.7-19.4 months (mean, 11.9 months). Complications included refracture (1 case), skin crease (1 case), lengthening failure (1 case), foot drop (2 cases), retractions of the transport segment (1 case), delay of mineralization (1 case), which were cured after corresponding treatment. According to Hohl knee evaluation system to assess knee joint function after removal of external fixator and intramedullary nail, the results were excellent in 15 cases, good in 5 cases, and fair in 2 cases, with an excellent and good rate of 90.9%; according to Baird-Jackson ankle evaluation system to evaluate ankle joint function, the results were excellent in 10 cases, good in 3 cases, fair in 7 cases, and poor in 2 cases, with an excellent and good rate of 59.1%.",
            "output": [
                "Do [ BONE TRANSPORTATION BY RING TYPE EXTERNAL FIXATOR COMBINED WITH LOCKED INTRAMEDULLARY NAIL FOR TIBIAL NON-INFECTIOUS DEFECT ]?"
            ]
        },
        {
            "id": "task847-e46ffa52f46745cd9e0cc911d7a4f858",
            "input": "Cancer-associated fibroblasts (CAFs) are believed to play an essential role in cancer initiation and development. However, little research has been undertaken to evaluate the role of CAFs in endometrial cancer (EC) progression. We aim to detect the functional contributions of CAFs to promote progression of EC.', 'Stromal fibroblasts were isolated from endometrioid adenocarcinomas and normal endometrial tissues. The conditioned media of cultured CAFs and normal fibroblasts (NFs) were collected to detect the level of stromal cell-derived factor-1alpha (SDF-1\u03b1), macrophage chemoattractant protein-1 (MCP-1), migration inhibitory factor (MIF), colony stimulating factor-1 (CSF-1), and interleukin-1 (IL-1) by ELISA. The CAFs or NFs were cocultured with EC cell lines to determine the proliferation, migration, and invasion by MTT assays and transwell chambers. Xenograft models were used to observe tumor growth. Matrix metalloproteinases (MMP)-2 and MMP-9 activity was evaluated by zymography. AMD3100 (a chemokine receptor 4 (CXCR4) antagonist) was used to block the SDF-1/CXCR4 axis. Neutralizing antibodies were used to detect PI3K/Akt and MAPK/Erk pathways by western blotting. SDF-1\u03b1 and CXCR4 expressions were analyzed in xenotransplanted tumors and 348 cases by immunohistochemistry.', 'CAFs promoted proliferation, migration, and invasion as well as in vivo tumorigenesis of admixed EC cells significantly more than NFs by secreting SDF-1\u03b1. These effects were significantly inhibited by AMD3100. CAFs promoted EC progression via the SDF-1\u03b1/CXCR4 axis to activate the PI3K/Akt and MAPK/Erk signalings in a paracrine-dependent manner or increase MMP-2 and MMP-9 secretion in an autocrine-dependent manner. SDF-1\u03b1 and CXCR4 expression upregulation accompanied clinical EC development and progression. High SDF-1\u03b1 expression levels were associated with deep myometrial invasion, lymph node metastasis, and poor prognosis in EC.",
            "output": [
                "Do cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis?"
            ]
        },
        {
            "id": "task847-d6647a7926724d379b3e6089b9a8da04",
            "input": "It is unknown whether receiving treatment that is discordant with practice guidelines is associated with improved survival in patients with nasopharyngeal carcinoma. The objectives of this study were to characterise national treatment patterns, analyse whether treatment outside of practice guidelines is associated with overall survival, and identify variables associated with receiving guidelines-discordant care in the USA.', 'This was a retrospective cohort study of 1741 nasopharyngeal carcinoma patients in the National Cancer Data Base (2003-2006). Treatment regimens were compared with the 2004-2006 National Comprehensive Cancer Network guidelines. Statistical analyses included chi-square, Kaplan-Meier, multivariable logistic, and Cox regression.', 'Nearly 26% of our cohort received care discordant with practice guidelines. In multivariable analysis, patients with stage IVC disease (odds ratio 2.59, 95% confidence interval 1.66-4.04) were more likely to receive guidelines-discordant care when compared with those with stage II-IVB disease. The most common treatment deviation for those with stage I disease was overtreatment with chemoradiation therapy. Receiving guidelines-discordant care was associated with an increased risk of death (hazard ratio 1.46, 95% confidence interval 1.25-1.69).",
            "output": [
                "Is receipt of Care Discordant with Practice Guidelines Associated with Compromised Overall Survival in Nasopharyngeal Carcinoma?"
            ]
        },
        {
            "id": "task847-cd01e9b9fba94fcaad819d09ab51fc23",
            "input": "It has been argued that carotid intima-media thickness (IMT) could better reflect an adaptive response of the vessel wall rather than being a marker of atherosclerosis. We explore this hypothesis by analyzing the ARTICO data.', 'The ARTICO study was designed to evaluate the prognostic value of the pathological ankle-brachial index (ABI) for the emergence of new vascular events in patients who have suffered a noncardioembolic stroke. Collected variables were as follows: vascular risk factors, mean waist perimeter, quantification of carotid IMT, characteristics of carotid plaques, ABI, and presence of microalbuminuria.', \"A total of 591 patients with a complete carotid evaluation were available. There was no correlation between ABI and IMT (Spearman's, p NS). Logistic regression revealed that pathological ABI correlated significantly only with internal carotid artery stenosis\\u2009greater than or equal to\\u200950% (OR [odds ratio] 2.80, 1.66-4.71, P\\u2009<\\u2009.01) and peripheral artery disease (OR 3.33, 1.63-6.78, P\\u2009<\\u2009.01). However, multivariate regression analysis demonstrated that carotid IMT was independently associated with age (OR 1.05, 95% confidence interval [CI] 1.02-1.09, P\\u2009<\\u2009.01), hypertension (OR 1.83, 95% CI 1.02-3.26, P\\u2009=\\u2009.04), waist circumference (OR 1.03, 95% CI 1.01-1.05, P\\u2009<\\u2009.01), and microalbuminuria (OR 2.02, 95% CI 1.22-3.35, P\\u2009<\\u2009.01).",
            "output": [
                "Is carotid Intima-Media Thickness Associated with Markers of Atherosclerosis in Stroke Patients?"
            ]
        },
        {
            "id": "task847-6975b986d2ea4b349b48e1d376585ca2",
            "input": "To establish a non-invasive model for the assessment of portal venous pressure (PVP) based on the magnetic resonance (MR) parameters.', 'In this prospective study, contrast-enhanced magnetic resonance imaging (MRI) scan was performed in 109 patients indicated for upper abdominal surgeries after their written consents were obtained, and intraoperative PVP measurements were completed in 92 patients. Altogether 17 patients were excluded for not undergoing surgery or unsuccessful catheterization. A linear model was constructed for estimating PVP levels in 56 patients and further validation was conducted in the other 36 patients.', \"The PVP levels were significantly correlated with MR parameters, including splenic volume (SV), splenic venous diameter (SVD), liver/splenic volume ratio, portal venous diameter, hepatic diameter, portal venous cross-sectional area, ascites, varices and arterial portal shunts. A linear model was established as follows: PVP (mmHg) = 2.529 + 1.572 \u00d7 SVD (mm) + 0.231 \u00d7 SV/body mass index (\u00d7 10(4) cm(5) /kg) + 3.44\\u2009\u00d7\\u2009aspartate aminotransferase-to-platelet ratio index. This model showed excellent accuracy in the detection of portal hypertension, with the area under the receiver operating characteristic curve (AUROC) of 0.945 (95% CI 0.867-1.000), with the sensitivity and specificity of 91.7% and 93.7%, respectively. The agreement analysis revealed that the predictive value using this formula closely reflected the patients' actual PVP level. Moreover, the validation confirmed the accuracy of this model for the assessment of portal hypertension [AUROC 0.935 (95% CI 0.856-1.000)].",
            "output": [
                "Does a non-invasive magnetic resonance imaging-based model predict portal venous pressure?"
            ]
        },
        {
            "id": "task847-bd8ff62fbb3a41818d6720298ef83b92",
            "input": "FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs in human cancers remain largely unknown. Aberrant expression and activation of Nrf2 often correlate with chemoresistance and poor prognosis. Here, we report that FoxO3 directs the basal transcription of Kelch-like ECH-associated protein 1 (Keap1), an adaptor protein that bridges Nrf2 to Cul3 for degradation. FoxO3 depletion resulted in Keap1 down-regulation, thereby activating Nrf2 signaling. We further demonstrated that inhibition of the FoxO3-Keap1 axis accounts for Nrf2 induction and activation induced by constitutively active AKT signaling or tumor necrosis factor \u03b1 treatment. Unlike previous findings, FoxO3 silencing led to decreased reactive oxygen species production, therefore protecting cells from oxidative stress-induced killing in an Nrf2-dependent manner. Importantly, FoxO3 deficiency strongly potentiated tumor formation in nude mice and rendered cholangiocarcinoma xenografts resistant to cisplatin-induced cell death by activating Nrf2. Additionally, we found that clinical cholangiocarcinoma samples displayed FoxO3-Keap1 down-regulation and Nrf2 hyperactivation, underscoring the essential roles of these proteins in cholangiocarcinoma development.",
            "output": [
                "Does foxO3 inactivation promote human cholangiocarcinoma tumorigenesis and chemoresistance through Keap1-Nrf2 signaling?"
            ]
        },
        {
            "id": "task847-ee1f26a8e05b4205a1fcc0db31f907be",
            "input": "Based on the data from elective surgical patients, positioning patients in a back-up head-elevated position for preoxygenation and tracheal intubation can improve patient safety. However, data specific to the emergent setting are lacking. We hypothesized that back-up head-elevated positioning would be associated with a decrease in complications related to tracheal intubation in the emergency room environment.', 'This retrospective study was approved by the University of Washington Human Subjects Division (Seattle, WA). Eligible patients included all adults undergoing emergent tracheal intubation outside of the operating room by the anesthesiology-based airway service at 2 university-affiliated teaching hospitals. All intubations were through direct laryngoscopy for an indication other than full cardiopulmonary arrest. Patient characteristics and details of the intubation procedure were derived from the medical record. The primary study endpoint was the occurrence of a composite of any intubation-related complication: difficult intubation, hypoxemia, esophageal intubation, or pulmonary aspiration. Multivariable logistic regression was used to estimate the odds of the primary endpoint in the supine versus back-up head-elevated positions with adjustment for a priori-defined potential confounders (body mass index and a difficult intubation prediction score [Mallampati, obstructive sleep Apnea, Cervical mobility, mouth Opening, Coma, severe Hypoxemia, and intubation by a non-Anesthesiologist score]).', 'Five hundred twenty-eight patients were analyzed. Overall, at least 1 intubation-related complication occurred in 76 of 336 (22.6%) patients managed in the supine position compared with 18 of 192 (9.3%) patients managed in the back-up head-elevated position. After adjusting for body mass index and the Mallampati, obstructive sleep Apnea, Cervical mobility, mouth Opening, Coma, severe Hypoxemia, and intubation by a non-Anesthesiologist score, the odds of encountering the primary endpoint during an emergency tracheal intubation in a back-up head-elevated position was 0.47 (95% confidence interval, 0.26-0.83; P = 0.01).",
            "output": [
                "Does head-Elevated Patient Positioning decrease Complications of Emergent Tracheal Intubation in the Ward and Intensive Care Unit?"
            ]
        },
        {
            "id": "task847-5aec0cdb04e746f2bb5e09927d223616",
            "input": "Joint instability is believed to promote early osteoarthritic changes in the knee. Inflammatory reactions are associated with cartilage degradation in osteoarthritis (OA) but their possible synergistic or additive effects remain largely unexplored. The goal of the present study was to investigate the in\\xa0vivo effects of Botulinum Toxin A (BTX-A) induced joint instability on intraarticular alterations in an otherwise intact rabbit knee joint model.', 'Ten 1-year-old female New Zealand White rabbits (average 5.7\\xa0kg, range 4.8-6.6\\xa0kg) were randomly assigned to receive three monthly unilateral intramuscular injections of BTX-A (experimental group), or no treatment (control group). After 90\\xa0days, all knees were analyzed for specific mRNA levels using RT-qPCR. The synovium and cartilage tissue was assessed for histological alterations using the OARSI scoring system.', 'Cartilage and synovial histology showed significant higher OARSI scores in the BTX-A group animals compared to the untreated controls and contralateral limbs. There were no differences between the untreated control and the contralateral experimental limbs. Gene expression showed significant elevations for collagen I, collagen III, nitric oxide, TGF-\u03b2, IL-1 and IL-6 compared to the healthy controls.",
            "output": [
                "Does joint instability lead to long-term alterations to knee synovium and osteoarthritis in a rabbit model?"
            ]
        },
        {
            "id": "task847-281025f5338a4ee182dff12219799cbd",
            "input": "The aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer.', 'Immunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells.', 'EGFR expression in tumor stroma correlated significantly with clinical stage (\u03c7 (2)=7.002, P=0.008) and distant metastases (\u03c7 (2)=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (\u03c7 (2)=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125-2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells.",
            "output": [
                "Are high levels of EGFR expression in tumor stroma associated with aggressive clinical features in epithelial ovarian cancer?"
            ]
        },
        {
            "id": "task847-a634485611c749ce93971b6ee10d17e6",
            "input": "Aluminum potroom exposure is associated with increased mortality of COPD but the association between potroom exposure and annual decline in lung function is unknown. We have measured lung volumes annually using spirometry from 1986 to 1996. The objective was to compare annual decline in forced expiratory volume in 1\\u2009s (dFEV1) and forced vital capacity (dFVC).', 'The number of aluminum potroom workers was 4,546 (81% males) and the number of workers in the reference group was 651 (76% males). The number of spirometries in the index group and the references were 24,060 and 2,243, respectively.', 'After adjustment for confounders, the difference in dFEV1 and dFVC between the index and reference groups were 13.5 (P\\u2009<\\u20090.001) and -8.0 (P\\u2009=\\u20090.060)\\u2009ml/year.",
            "output": [
                "Is annual decline in forced expiratory volume steeper in aluminum potroom workers than in workers without exposure to potroom fumes?"
            ]
        },
        {
            "id": "task847-755b8cc43fc94de19775f0cd9699484b",
            "input": "The observation of intact non-covalent complexes by electrospray ionization mass spectrometry (ESI-MS) hinges on the ability to minimize in-source activation processes that take place during analyte desolvation. We explored the merits of replacing the sampling cone of a standard Z-spray source with a heated capillary that makes the desolvation process slower and more gradual. We employed well-characterized protein-RNA, RNA-RNA, and DNA-DNA assemblies to compare the alternative configurations.', 'Mass analysis evaluated the integrity of the complexes, whereas traveling wave ion mobility experiments assessed the stability of biomolecular structure. Analyses were performed back-to-back on the same samples on a Synapt G2 HDMS equipped with either the standard sampling cone or the heated-capillary apparatus. In each configuration, the source/capillary temperature was varied in controlled fashion, while keeping all other desolvation parameters constant to monitor the in-source dissociation of selected DNA duplexes. Ion mobility data were obtained from the same precursor by using the alternative configurations under the same settings.', 'Monitoring the percentage of associated complex demonstrated that the heated capillary provided softer desolvation that was more conducive to the detection of intact non-covalent interactions. This configuration failed to produce complete dissociation of 14\\u2009bp and 24\\u2009bp duplexes, even when the source/capillary temperature was increased well above their solution melting points. Analyzed by IMS-MS, a selected construct displayed just one conformation with the heated capillary, but two with the standard sampling cone.",
            "output": [
                "Does a simple heated-capillary modification improve the analysis of non-covalent complexes by Z-spray electrospray ionization?"
            ]
        },
        {
            "id": "task847-463ab76282db40019a3b99c66cd49240",
            "input": "To investigate the effect of initial varus or valgus surgical neck alignment on outcomes of patients who sustained proximal humerus fractures treated with open reduction and internal fixation (ORIF).', 'An institutional review board approved database of proximal humerus fractures treated with locked plates was reviewed. Of 185 fractures in the database, 101 fractures were identified and met inclusion criteria. Initial varus displacement was seen in 47 fractures (OTA types 11.A2.2, A3.1, A3.3, B1.2, B2.2, C1.2, C2.2, or C2.3) and initial valgus displacement was observed in 54 fractures (OTA types 11.A2.3, B1.1, C1.1, or C2.1). All patients were treated in a similar manner and examined by the treating physician at standard intervals. Functional outcomes were quantified via the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and physical examination data at 12 months. Radiographs were reviewed for complications of healing. Additionally, complication rate and reoperation rate were investigated.', 'Patients who presented with initial varus displacement had an average age of 59.3 years, while patients in the valgus group had an average age of 62.4 years. Overall, there was no statistically significant difference in age, sex distribution, BMI, fracture parts, screws used, or implant plate type between the two groups. At a minimum 12 months follow up, there was no significant difference in DASH scores between those presenting with varus versus valgus fracture patterns. In addition, no significant differences were seen in final shoulder range of motion in any plane. Overall, 30 patients included in this study developed a complication. A significantly greater number of patients in the initial varus cohort developed complications (40.4%), as compared to 20.3% of patients in the initial valgus cohort (P=0.03). Fourteen patients in this study underwent reoperation. Nine of these patients were in the varus cohort, while 5 were in the valgus cohort (P=0.15).",
            "output": [
                "Does initial varus displacement of proximal humerus fractures result in similar function but higher complication rates?"
            ]
        },
        {
            "id": "task847-98eb6c55e13c4b268cf463e96f677fea",
            "input": "Thigmotaxis refers to a specific behavior of animals (i.e., to stay close to walls when exploring an open space). Such behavior can be assessed with the open field test (OFT), which is a well-established indicator of animal fear. The detection of similar open field behavior in humans may verify the translational validity of this paradigm. Enhanced thigmotaxis related to anxiety may suggest the relevance of such behavior for anxiety disorders, especially agoraphobia.', 'A global positioning system was used to analyze the behavior of 16 patients with agoraphobia and 18 healthy individuals with a risk for agoraphobia (i.e., high anxiety sensitivity) during a human OFT and compare it with appropriate control groups (n = 16 and n = 19). We also tracked 17 patients with agoraphobia and 17 control participants during a city walk that involved walking through an open market square.', 'Our human OFT triggered thigmotaxis in participants; patients with agoraphobia and participants with high anxiety sensitivity exhibited enhanced thigmotaxis. This behavior was evident in increased movement lengths along the wall of the natural open field and fewer entries into the center of the field despite normal movement speed and length. Furthermore, participants avoided passing through the market square during the city walk, indicating again that thigmotaxis is related to agoraphobia.",
            "output": [
                "Does a Human Open Field Test reveal Thigmotaxis Related to Agoraphobic Fear?"
            ]
        },
        {
            "id": "task847-4ca84f156a8f463fbed78f04bcf6f959",
            "input": "To determine fetal thymus growth and its relationship with fetal weight and cord blood T-regulatory cells in a prospective study. Assessment of fetal immune organs by ultrasound could provide a screening approach to identify fetuses at risk of impaired postnatal immunity.', 'Thymus size was measured with four ultrasound techniques. The approaches with lowest coefficient of variation (thymus transverse diameter, 3 vessel edge) were used to longitudinally assess fetal and thymus growth in 137 cases at four time points between a gestational age (GA) of 13 and 37 weeks. Cord blood at birth was analyzed by flow-cytometry to evaluate the frequency of regulatory T (Treg) cells.",
            "output": [
                "Does fetal thymus size in human pregnancies reveal inverse association with regulatory T cell frequencies in cord blood?"
            ]
        },
        {
            "id": "task847-3c0583e6a8794482be54746de43b0515",
            "input": "Dengue is a mosquito-borne viral disease caused by the four dengue viruses (DENV-1 to 4) that can also be transmitted by blood transfusion and organ transplantation. The distribution of DENV in the components of blood from infected donors is poorly understood.', 'We used an in-house TaqMan qRT-PCR assay to test residual samples of plasma, cellular components of whole blood (CCWB), serum and clot specimens from the same collection from blood donors who were DENV-RNA-reactive in a parallel blood safety study. To assess whether DENV RNA detected by TaqMan was associated with infectious virus, DENV infectivity in available samples was determined by culture in mosquito cells.', 'DENV RNA was detected by TaqMan in all tested blood components, albeit more consistently in the cellular components; 78.8% of CCWB, 73.3% of clots, 86.7% of sera and 41.8% of plasma samples. DENV-1 was detected in 48 plasma and 97 CCWB samples while DENV-4 was detected in 21 plasma and 31 CCWB samples. In mosquito cell cultures, 29/111 (26.1%) plasma and 32/97 (32.7%) CCWB samples were infectious. A subset of samples from 29 donors was separately analyzed to compare DENV viral loads in the available blood components. DENV viral loads did not differ significantly between components and ranged from 3-8 log10 PCR-detectable units/ml.",
            "output": [
                "Does distribution of Dengue Virus type 1 and 4 in Blood Components from Infected Blood Donors from Puerto Rico?"
            ]
        },
        {
            "id": "task847-0a134c321dc044e189fb0b2a3f80a9f7",
            "input": "The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in\\xa0vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress.', 'Raw 264.7 cells were pretreated with GRo (up to 200\u03bcM) for 1\\xa0h before treatment with 1\\xa0\u03bcg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated.', 'GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells.",
            "output": [
                "Does upregulation of heme oxygenase-1 by ginsenoside Ro attenuate lipopolysaccharide-induced inflammation in macrophage cells?"
            ]
        },
        {
            "id": "task847-d5ead6d8b4cf47a0884247de8c0056e9",
            "input": "Both Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) might increase the risk of suicidal behavior. The aim of this study was to assess the relationship between personality dimensions specifically involved in suicidal vulnerability and PMS/PMDD.', 'We collected data from 232 women consecutively hospitalized after a suicide attempt. We examined the relationship between impulsivity, aggressiveness/hostility, hopelessness, trait anger, affect intensity, emotional lability, and PMS/PMDD. Notably, we created an algorithm from the shortened Premenstrual Assessment form in order to assess PMDD status.', 'The proportions of PMS and PMDD among female suicide attempters were 50% and 23% respectively. Women with PMS or PMDD were more likely to endorse most of these personality traits to than those without even after controlling for potential confounders. We found an impulsive-aggressive pattern of personality in women with PMS or PMDD, independently from the time of the menstrual cycle. Interestingly, trait anger remained associated with both PMS and PMDD independently of every other personality traits. The higher the anger level, the higher the risk was to suffer from both PMS and PMDD.",
            "output": [
                "Do personality Traits of Suicidality Are Associated with Premenstrual Syndrome and Premenstrual Dysphoric Disorder in a Suicidal Women Sample?"
            ]
        },
        {
            "id": "task847-edceb5cc60f34968bfadd38212556cb3",
            "input": "Low lean mass (LM) is a risk factor for chronic disease, a major cause of disability and diminished quality of life, and is a heritable trait. However, relatively few specific genetic factors have been identified as potentially influencing this trait.', \"In this study, we selected 1493 single-nucleotide polymorphisms (SNP) in 155 candidate genes involved in anabolic, catabolic, growth hormone, and other related pathways and examined their association with LM, assessed by dual-energy x-ray absorptiometry, in a sample of 2760 non-Hispanic and Hispanic white postmenopausal women from the Women's Health Initiative (WHI) Observational Study. We assessed the replication of our top findings in a meta-analysis of 20 genome-wide association studies (n = 38,292) conducted by the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Musculoskeletal Working Group.\", 'We identified 32 SNPs that had nominally significant associations with LM in the WHI cohort. In the replication stage, we find that SNP rs2276541 in the activin A receptor, type IIB (ACVR2B), was significantly associated with LM (\u03b2 = 0.15, P = 2.17 \u00d7 10). ACVR2B codes for a receptor for a negative regulator of skeletal muscle, myostatin, and has previously been identified in a candidate gene study as a determinant of skeletal muscle mass.",
            "output": [
                "Does genetic Variant in ACVR2B be Associated with Lean Mass?"
            ]
        },
        {
            "id": "task847-bdd4baee7c6c4405837b149c5f794be9",
            "input": "Systemic sclerosis (SSc) is a connective-tissue disease characterized by vascular injury, immune-system disorders, and excessive fibrosis of the skin and multiple internal organs. Recent reports found that RhoA/Rho-kinase (ROCK) pathway is implicated in various fibrogenic diseases. Intradermal injection of hypochlorous acid (HOCl)-generating solution induced inflammation, autoimmune activation, and fibrosis, mimicking the cutaneous diffuse form of SSc in humans. Our study aimed firstly to describe pulmonary inflammation and fibrosis induced by HOCl in mice, and secondly to determine whether fasudil, a selective inhibitor of ROCK, could prevent lung and skin fibroses in HOCl-injected mice.', 'Female C57BL/6 mice received daily intradermal injection of hypochlorous acid (HOCl) for 6 weeks to induce SSc, with and without daily treatment with fasudil (30\\xa0mg\u00b7kg(-1)\u00b7day(-1)) by oral gavage.', 'HOCl intoxication induced significant lung inflammation (macrophages and neutrophils infiltration), and fibrosis. These modifications were prevented by fasudil treatment. Simultaneously, HOCl enhanced ROCK activity in lung and skin tissues. Inhibition of ROCK reduced skin fibrosis, expression of \u03b1-smooth-muscle actin and 3-nitrotyrosine, as well as the activity of ROCK in the fibrotic skin of HOCl-treated mice, through inhibition of phosphorylation of Smad2/3 and ERK1/2. Fasudil significantly decreased the serum levels of anti-DNA-topoisomerase-1 antibodies in mice with HOCl-induced SSc.",
            "output": [
                "Does rhoA/Rho-kinase activation promote lung fibrosis in an animal model of systemic sclerosis?"
            ]
        },
        {
            "id": "task847-30d437506fe84db996490ff259ea4e53",
            "input": "Human papillomavirus (HPV) is a common sexually transmitted infection that causes anal, penile, and oropharyngeal cancers in men. Men who have sex with men (MSM) are at particularly high risk for HPV infection and HPV-related disease. Human papillomavirus vaccination is currently recommended for all MSM in the United States through age 26 years, yet little is known about HPV vaccine uptake in this population. The purpose of this study was to identify predictors of HPV vaccine uptake and barriers and facilitators to HPV vaccination that may be unique to young MSM.', 'Men aged 18 to 26 years (n = 336) were recruited via advertisements placed on a geospatial smartphone dating application designed for MSM. Participants completed an online survey. Correlates of vaccine uptake and provider recommendation for HPV vaccine were identified using logistic regression.', 'In total, 21% of participants had received at least 1 dose of HPV vaccine. Provider recommendation was the strongest predictor of uptake such that MSM with a recommendation were more than 40 times more likely to have been vaccinated. Additional predictors of uptake included age and HPV vaccine attitudes. Predictors of provider recommendation included sexual identity, race/ethnicity, condomless anal sex, and HIV status. Psychosocial correlates and barriers and facilitators to HPV vaccination among unvaccinated men were also identified.",
            "output": [
                "Do predictors of Human Papillomavirus Vaccination Among Young Men Who Have Sex With Men?"
            ]
        },
        {
            "id": "task847-380c991f1a584b6ca6e1cfd41deee4cd",
            "input": "NAFLD impacts patient reported outcomes (PROs). Our aim was to assess the impact of NAFLD on patients' HRQOL.\", 'National Health and Nutrition Examination Survey (NHANES) 2001-2011 data were used to identify adult patients with NAFLD [Fatty Liver Index (FLI) > 60 in absence of other liver disease and excessive alcohol >20 g/day for men, >10 g/day for women]. Patients with other chronic diseases (ex. HIV, cancer, end-stage kidney disease) were excluded. Subjects without any of these conditions were healthy controls. HCV RNA (+) patients were HCV-controls. All patients completed NHANES HRQOL-4 questionnaire. Linear regression determined the association between NAFLD and HRQOL components adjusting for age, gender, race, and BMI.', 'Participants with complete data were included (n = 9661); 3333 NAFLD (age 51 years and BMI 34 kg/m(2)); 346 HCV+ (age 49 years; BMI 27 kg/m(2)) and 5982 healthy controls (age 48 years and BMI 26 kg/m(2)). The proportion of subjects rating their health as \"fair\" or \"poor\" in descending order were HCV controls (30 %) NAFLD (20 %) and healthy controls (10 %) (p < 0.001). HRQOL-4 components scores 2-4 were lowest for HCV, followed by NAFLD and then healthy controls (p-values p = 0.011 to < .0001). After adjustment for age, gender, race, and BMI, NAFLD patients were 18-20 % more likely to report days when their physical health wasn\\'t good or were unable to perform daily activities as a result (p < .0001).",
            "output": [
                "Is non-alcoholic Fatty Liver Disease ( NAFLD ) associated with impairment of Health Related Quality of Life ( HRQOL )?"
            ]
        },
        {
            "id": "task847-6277828b15824bc0ae78b9893597d4b5",
            "input": "Human heart valves are prone to glycation, a fundamental process of ageing. The aim of this study was to establish the relationship between fructosamine formation and the mechanical properties of human aortic valves.', '67 patients (age: 76\u00b18\\u2005years) diagnosed with an aortic valve stenosis, who underwent an aortic valve replacement were enrolled. Fructosamine and calcium concentrations in aortic valves were determined. Using a transthoracic Doppler echocardiography, aortic valve orifice area and transvalvular pressure gradients were measured. In a subgroup of 32 patients, the aortic valve orifice area was sufficient to carry out mechanical testing on a LFPlus Universal material tester. An in vitro removal of fructosamine of the valve was initiated using ATP-dependent fructosamine 3-kinase (FN3K).', 'A significant correlation was found between the aortic valve fructosamine concentration and the calculated aortic valve orifice area: Y (aortic valve orifice area, mm(2))=1.050-0.228X (aortic valve fructosamine concentration, \u00b5mol/g valve) (r=-0.38). A significantly higher calcium concentration was measured in the aortic valves of diabetics in comparison with those of non-diabetics. A multiple regression analysis revealed that the presence of diabetes mellitus and aortic valve fructosamine concentration were the main predictors of the extensibility of the aortic valves. In the in vitro deglycation study, a significant lower aortic valve fructosamine concentration was detected after treatment with FN3K. This resulted in an increased flexibility of the aortic valves.",
            "output": [
                "Is the presence of fructosamine in human aortic valves associated with valve stiffness?"
            ]
        },
        {
            "id": "task847-4ce569e2d7cb402299fda890483370a1",
            "input": "T2 Lesion Volume (T2LV) has been an important biomarker for multiple sclerosis (MS). Current methods available to quantify lesions from MR images generally require manual adjustments or multiple images with different contrasts. Further, implementations are often not easily or openly accessible.', 'We created a fully unsupervised, single T2 FLAIR image T2LV quantification package based on the popular open-source imaging toolkit FSL.', 'By scripting various processing tools in FSL, we developed an image processing pipeline that distinguishes normal brain tissue from CSF and lesions. We validated our method by hierarchical multiple regression (HMR) with a preliminary study to see if our T2LVs correlate with clinical disability measures in MS when controlled for other variables.', 'Pearson correlations between T2LV and Expanded Disability Status Scale (EDSS: r = 0.344, P = 0.013), Six-Minute Walk (6MW: r = -0.513, P = 0.000), Timed 25-Foot Walk (T25FW: r = -0.438, P = .000), and Symbol Digit Modalities Test (SDMT: r = -0.499, P = 0.000) were all significant. Partial correlations controlling for age were significant between T2LV and 6MW (r = -0.433, P = 0.002), T25FW (r = -0.392, P = 0.004), and SDMT (r = -0.450, P = 0.001). In HMR, T2LV explained significant additional variance in 6MW (R(2) change = 0.082, P = 0.020), after controlling for confounding variables such as age, white matter volume (WMV), and gray matter volume (GMV).",
            "output": [
                "Does fully automated open-source lesion mapping of T2-FLAIR images with FSL correlate with clinical disability in MS?"
            ]
        },
        {
            "id": "task847-74d9ace1bca24ba0a24a7575e502d23d",
            "input": "We previously reported that vascular endothelial growth factor (VEGF)-induced binding of VEGF receptor 2 (VEGFR2) to epsins 1 and 2 triggers VEGFR2 degradation and attenuates VEGF signaling. The epsin ubiquitin interacting motif (UIM) was shown to be required for the interaction with VEGFR2. However, the molecular determinants that govern how epsin specifically interacts with and regulates VEGFR2 were unknown.', 'The goals for the present study were as follows: (1) to identify critical molecular determinants that drive the specificity of the epsin and VEGFR2 interaction and (2) to ascertain whether such determinants were critical for physiological angiogenesis in vivo.', 'Structural modeling uncovered 2 novel binding surfaces within VEGFR2 that mediate specific interactions with epsin UIM. Three glutamic acid residues in epsin UIM were found to interact with residues in VEGFR2. Furthermore, we found that the VEGF-induced VEGFR2-epsin interaction promoted casitas B-lineage lymphoma-mediated ubiquitination of epsin, and uncovered a previously unappreciated ubiquitin-binding surface within VEGFR2. Mutational analysis revealed that the VEGFR2-epsin interaction is supported by VEGFR2 interacting specifically with the UIM and with ubiquitinated epsin. An epsin UIM peptide, but not a mutant UIM peptide, potentiated endothelial cell proliferation, migration and angiogenic properties in vitro, increased postnatal retinal angiogenesis, and enhanced VEGF-induced physiological angiogenesis and wound healing.",
            "output": [
                "Does selective Targeting of a Novel Epsin-VEGFR2 Interaction promote VEGF-Mediated Angiogenesis?"
            ]
        },
        {
            "id": "task847-e64f5cf2732348789551d6072a515769",
            "input": "The archeological record indicates that the permanent settlement of Cyprus began with pioneering agriculturalists circa 11,000\\xa0years before present, (ca. 11,000 y BP). Subsequent colonization events followed, some recognized\\xa0regionally. Here, we assess the Y-chromosome structure of Cyprus in context to regional populations and correlate it to phases of prehistoric colonization.', 'Analysis of haplotypes from 574 samples showed that island-wide substructure was barely significant in a spatial analysis of molecular variance (SAMOVA). However, analyses of molecular variance (AMOVA) of haplogroups using 92 binary markers genotyped in 629 Cypriots revealed that the proportion of variance among the districts was irregularly distributed. Principal component analysis (PCA) revealed potential genetic associations of Greek-Cypriots with neighbor populations. Contrasting haplogroups in the PCA were used as surrogates of parental populations. Admixture analyses suggested that the majority of G2a-P15 and R1b-M269 components were contributed by Anatolia and Levant sources, respectively, while Greece Balkans supplied the majority of E-V13 and J2a-M67. Haplotype-based expansion times were at historical levels suggestive of recent demography.",
            "output": [
                "Does y-chromosome phylogeographic analysis of the Greek-Cypriot population reveal elements consistent with Neolithic and Bronze Age settlements?"
            ]
        },
        {
            "id": "task847-628b8383878c47e9952f97e0e888e544",
            "input": "Vancomycin loading doses are recommended; however, the risk of nephrotoxicity with these doses is unknown. The primary objective of this study was to compare nephrotoxicity in emergency department (ED) sepsis patients who received vancomycin at high doses (>20 mg/kg) versus lower doses (\u226420 mg/kg).', 'A retrospective cohort study was performed in three academic EDs. Inclusion criteria were age \u2265 18 years, intravenous vancomycin order, and hospital admission. Exclusion criteria were no documented weight, hemodialysis-dependent, and inadequate serum creatinine (SCr) values for the measured outcome. Analyses compared the incidence of nephrotoxicity for patients who received vancomycin at high dose (>20 mg/kg) versus low dose (\u226420 mg/kg).', 'A total of 2,131 consecutive patients prescribed vancomycin over 6 months were identified. Of these, 1,330 patients had three SCr values assessed for the primary outcome. High-dose initial vancomycin was associated with a significantly lower rate of nephrotoxicity (5.8% vs. 11.1%). After age, sex, and initial SCr were adjusted for, the risk of high-dose vancomycin compared to low-dose was decreased for the development of nephrotoxicity (relative risk = 0.60; 95% confidence interval = 0.44 to 0.82).",
            "output": [
                "Is high Single-dose Vancomycin Loading Associated With Increased Nephrotoxicity in Emergency Department Sepsis Patients?"
            ]
        },
        {
            "id": "task847-b8559d0a076a42f8b3b1bd5967b4ea60",
            "input": "Ulcerative colitis and Crohn's disease frequently cause epithelial damage in the intestine, leading to gut inflammation accompanied by areas of ulceration. The regeneration of damaged mucosa as well as the restoration of intestinal homeostasis involve induced and coordinated proliferation and migration of intestinal epithelial cells. Commensal bacterial colonization of the intestine is essential for normal intestinal development, renewal, and repair. N-formyl peptide receptors (FPRs) are widely expressed pattern recognition receptors that can specifically bind and induce responses to host-derived and bacterial peptides and small molecules during repair of mucosal injury in a redox dependent manner. However, little is known about the host-microbiota crosstalk mediated by FPRs during repair of gut mucosal injuries. Herein, purpose of this study is to exploit the mechanism of mucosal healing promoted by a consortium of gut microbiota that preferentially colonizes ulcerated mucosa undergoing resealing.\", 'The regeneration of injured epithelial was studied using defined mechanical wounds inflicted in the mouse distal colon by employing a miniature endoscope and forceps. Microbiota studies were performed by high throughput sequencing of the V4 region of 16s rRNA gene of the bacteria harvested from mucosal wounds undergoing different stages of regenerative events.', 'The high throughput sequencing analysis of bacterial 16s rDNA determined rapid, reversible spatiotemporal alterations in the composition and diversity of microbiota in the wound microenvironment. Our data demonstrated that these ecological changes are dependent on FPR1/NOX2-mediated local tissue hypoxia, depletion of muc2 mucin, and compensatory effect of the over expression of HIF1-regulated MUC3 mucin. Our data show that these events of mucosal regeneration enrich a dominant member of this wound-associated consortium, Akkermansia muciniphila, which is associated with the pro-restitutive function. A. muciniphila, an anaerobic, mucinophilic commensal bacterium, enhanced proliferation and migration of enterocytes adjacent to the colonic wound beds in a process involving FPR1/NOX1 dependent redox signaling.",
            "output": [
                "Does o-012 The Intestinal Wound Regeneration modulate Mucosal Microenvironment to Stimulate Expansion of a Local Pro-restitutive Microbiota?"
            ]
        },
        {
            "id": "task847-2a282455e5594062ac1081a210e655dc",
            "input": "Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-\u03baB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD).', 'Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The association between SNPs and susceptibility to IPD and IMD, mortality and pneumococcal serotypes was investigated.', '372 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were included. We included 406 cases with meningococcal meningitis, 272 with meningococcal bacteremia, and 672 controls. The NFKBIE SNP was associated with increased risk of pneumococcal meningitis (aOR 1.68; 95% CI: 1.20-2.36), but not bacteremia (aOR 1.08; 95% CI: 0.86-1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality.",
            "output": [
                "Does genetic Variation in NFKBIE be Associated With Increased Risk of Pneumococcal Meningitis in Children?"
            ]
        },
        {
            "id": "task847-30120fd557b8452f8a65fa5fcc97a8aa",
            "input": "To test whether phosphorylated Ser-1292 LRRK2 levels in urine exosomes predicts LRRK2 mutation carriers (LRRK2+) and noncarriers (LRRK2-) with Parkinson disease (PD+) and without Parkinson disease (PD-).', 'LRRK2 protein was purified from urinary exosomes collected from participants in 2 independent cohorts. The first cohort included 14 men (LRRK2+/PD+, n = 7; LRRK2-/PD+, n = 4; LRRK2-/PD-, n = 3). The second cohort included 62 men (LRRK2-/PD-, n = 16; LRRK2+/PD-, n = 16; LRRK2+/PD+, n = 14; LRRK2-/PD+, n = 16). The ratio of Ser(P)-1292 LRRK2 to total LRRK2 was compared between LRRK2+/PD+ and LRRK2- in the first cohort and between LRRK2 G2019S carriers with and without PD in the second cohort.', 'LRRK2+/PD+ had higher ratios of Ser(P)-1292 LRRK2 to total LRRK2 than LRRK2-/PD- (4.8-fold, p < 0.001) and LRRK2-/PD+ (4.6-fold, p < 0.001). Among mutation carriers, those with PD had higher Ser(P)-1292 LRRK2 to total LRRK2 than those without PD (2.2-fold, p < 0.001). Ser(P)-1292 LRRK2 levels predicted symptomatic from asymptomatic carriers with an area under the receiver operating characteristic curve of 0.844.",
            "output": [
                "Does urinary LRRK2 phosphorylation predict parkinsonian phenotypes in G2019S LRRK2 carriers?"
            ]
        },
        {
            "id": "task847-d7bc47421d2a40c9ac5dbd937c50714b",
            "input": "To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society.', 'In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33\u00b0C vs 36\u00b0C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3-5 until 180 days.', 'Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p < 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome.",
            "output": [
                "Does standardized EEG interpretation accurately predict prognosis after cardiac arrest?"
            ]
        },
        {
            "id": "task847-228534a87e7d4e9dafd80dc24179882c",
            "input": "To investigate the clinical significance of Oct-4 in the development and progression of gastric cancer.', 'Immunohistochemistry was used to analyze Oct-4 expression in 412 gastric cancer cases. Oct-4 protein levels were upregulated in gastric cancer tissues compared with adjacent noncancerous tissues.', 'Positive expression of Oct-4 correlated with age, depth of invasion, Lauren classification, lymph node metastasis, distant metastasis, and TNM stage. In stages I, II, and III, the 5-year survival rate of patients with high expression of Oct-4 was significantly lower than that in patients with low expression of Oct-4. In stage IV, Oct-4 expression did not correlate with the 5-year survival rate. Furthermore, multivariate analysis suggested that the depth of invasion, lymph node metastasis, distant metastasis, TNM stage, and upregulation of Oct-4 were independent prognostic factors of gastric cancer.",
            "output": [
                "Is oct-4 associated with gastric cancer progression and prognosis?"
            ]
        },
        {
            "id": "task847-8195b15ced0b4ded879965afa124cf56",
            "input": "The present authors examined how patient hand contamination was associated with underlying disease and treatment environment in order to determine effective hand hygiene methods.', 'Samples were collected from inpatients (45 with hematological malignancies, 48 postoperative), outpatients (48 undergoing hemodialysis, 55 on chemotherapy), and 44 individuals living in nursing homes. All participants provided informed consent for study participation. All subjects performed hand hygiene. Before and after hand hygiene, samples of bacteria were collected from the palm of the hand onto agar media. Bacteria were counted and bacterial strains were identified. The authors then collected smear samples from the contralateral palm and measured adenosine triphosphate (ATP) levels.', 'Patient hand contamination was the highest in hemodialysis patients, followed by residents of nursing homes, postoperative patients, patients with cancer receiving chemotherapy, and patients of hematological malignancies. Regardless of the underlying disease and treatment environment, patients were able to reduce the number of bacterial colonies and ATP by proper hand hygiene. Compared with wet wipes, hand washing seemed to remove bacteria more effectively. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 30 subjects, none of whom were patients of hematological malignancies. Of these, 19 tested negative for MRSA after performing proper hand hygiene.",
            "output": [
                "Does effectiveness of hand hygiene depend on the patient 's health condition and care environment?"
            ]
        },
        {
            "id": "task847-4b8e1b8aeb8d4ebdb7028008d12882db",
            "input": "The similar clinical and pathological feature in fluorosis and amelogenesis imperfect with FAM83H mutations imply that excess fluoride could have effects on the expression of FAM83H and could elaborate this process by some signal pathways regulation. The present study aims to investigate the effects of fluoride on Fam83h expression and try to explore the molecular signaling regulation between them as well as the association of high concentration fluoride with mineralization in ameloblast lineage cells.', 'Protein expression and signaling pathways of mouse ameloblast-like LS8 cells, exposed to fluoride or MAPK inhibitors, were compared to control cells without exposure. Fam83h, proteins of MAPK signal pathways (ERK, P38 and JNK) were examined by Quantitative real-time PCR and/or Western-blot. ALP activity and ALP staining were used to detect the mineralization in the cells with exposure during 7-day mineralization inducing differentiation.', 'The results showed that Fam83h protein level in LS8 cells decreased in the presence of fluoride and MAPK inhibitors. Down-regulation of Fam83h by fluoride was related to suppression of JNK and P38 phosphorylation, and the descending degree of P38 was more obvious. Fluoride and MAPK inhibitors treatment significantly decreased the mineralization level in LS8 cells.",
            "output": [
                "Does p38/JNK signaling pathway mediate the fluoride-induced down-regulation of Fam83h?"
            ]
        },
        {
            "id": "task847-ae29b1d1c04e469a93983b91e159b05c",
            "input": "CT density correlates with quality of life (QOL) scores and impaired upper zone lung density associates with higher mortality in alpha one antitrypsin deficiency (A1ATD). We hypothesised that decline in CT densitometry would relate to survival or deterioration in QOL in A1ATD.', 'All augmentation na\u00efve PiZZ patients in the UK A1ATD registry with \u2265 two successive quantitative CT scans were selected. Patients were divided into groups based on CT density decline and the relationship to survival and change in QOL compared by univariate analyses and multivariate Cox regression. Analyses were performed for whole lung, upper zone and lower zone density separately. Exploratory analyses of FEV1 subgroups were conducted.', '110 patients were identified; 77 had whole lung and lung zone density recorded on two CT scans, 33 patients had upper zone data only on four scans. Decline in lower zone density associated with survival, even after adjustment for baseline lung density (p = 0.048), however upper zone density and whole lung density decline did not. This difference appeared to be driven by those with FEV1 >30% predicted.",
            "output": [
                "Does lung density associate with survival in alpha 1 antitrypsin deficient patients?"
            ]
        },
        {
            "id": "task847-66e8cbf57251485c992006e6a781647d",
            "input": "Bone graft to reconstruct the temporomandibular joint for ankylosis patient is effective. This study used three-dimensional measurement to evaluate the effect between free coronoid process graft (CPG) and costochondral graft (CCG) in the temporomandibular joint reconstruction.', 'Patients treated with CPG or CCG from 2011 to 2014 were included in the study. Postoperative computed tomography scan data within 1 week and during at least 6 months follow-up after operation were imported into Proplan CMF 1.4 software (Materialize, Belgium) for three-dimensional reconstruction and measurement. Heights of the mandibular ramus were measured and compared between the 2 groups. Maximum mouth opening and occlusion were also evaluated and compared before and after operation.', 'Ten patients with 15 reconstructed joints were included in the study. In the CPG group, the decrease of ramus height was 5.4 mm after a mean follow-up period of 16.8 months (ranged from 6 to 22 months), whereas in the CCG group, it was 2.4 mm after a mean follow-up period of 14.4 months (ranged from 6 to 30 months). There was significant difference of ramus height decrease between the CPG group and the CCG group (P < 0.05). Maximum mouth opening was significantly increased after operation than before in both groups (P < 0.05). Open bite happened in 4 of 5 patients in the CPG group, and 1 of 5 patients in the CCG group.",
            "output": [
                "Do a Comparison of the Effect Between Coronoid Process Graft and Costochondral Graft in the Reconstruction of Temporomandibular Joint?"
            ]
        },
        {
            "id": "task847-8b2a6d7fb8794ffbb17b05b8c22bdeca",
            "input": "The value of performing transthoracic echocardiography (TTE) as part of the clinical assessment of patients awaiting endovascular repair of the abdominal aorta is little evaluated. We aimed to estimate the prognostic importance of information derived from TTE on long-term all-cause mortality in a selected group of patients undergoing endovascular aneurysm repair.', 'This was a retrospective cohort study of 273 consecutive patients selected for endovascular aneurysm repair. All patients included in the analysis underwent TTE before their procedure. Multivariable Cox regression analysis was used to estimate the effect of TTE measures on all-cause mortality. Over a mean follow-up of 3.2\u00b11.5 years, there were 78 deaths with a mean time to death of 1.28\u00b11.16 years. A greater tubular ascending aorta (hazard ratio [HR] 5.6, 95% confidence interval [CI] 2.77-11.33), presence of mitral regurgitation (HR 8.13, 95% CI 4.09-12.16), lower left ventricular ejection fraction (HR 0.96, 95% CI 0.93-0.98), younger age (HR 0.97, 95% CI 0.95-0.99), and presence of diabetes mellitus (HR 1.46, 95% CI 1.24-1.89) were predictors of all-cause mortality.",
            "output": [
                "Does transthoracic Echocardiography provide Important Long-Term Prognostic Information in Selected Patients Undergoing Endovascular Abdominal Aortic Repair?"
            ]
        },
        {
            "id": "task847-4e2e81a3795e448c82696c8216dd71bd",
            "input": "The differential diagnosis of follicular thyroid carcinoma (FTC) and follicular adenoma (FA) before surgery is a clinical challenge. Many efforts have been made but most focusing on tumor cells, while the roles of tumor associated macrophages (TAMs) remained unclear in FTC. Here we analyzed the differences between TAMs in FTC and those in FA.', 'We first analyzed the density of TAMs by CD68 immunostaining in 59 histologically confirmed FTCs and 47 FAs. Cytokines produced by FTC and FA were profiled using antibody array, and validated by quantitative PCR. Chemotaxis of monocyte THP-1 was induced by condition medium of FTC cell lines (FTC133 and WRO82-1) with and without anti-CCL15 neutralizing antibody. Finally, we analyzed CCL15 protein level in FTC and FA by immunohistochemistry.', 'The average density of CD68(+) cells was 9.5 \u00b1 5.4/field in FTC, significantly higher than that in FA (4.9 \u00b1 3.4/field, p < 0.001). Subsequently profiling showed that CCL15 was the most abundant chemokine in FTC compared with FA. CCL15 mRNA in FTC was 51.4-folds of that in FA. CM of FTC cell lines induced THP-1 cell chemotaxis by 33 ~ 77%, and anti-CCL15 neutralizing antibody reduced THP-1 cell migration in a dose-dependent manner. Moreover, we observed positive CCL15 immunostaining in 67.8% of FTCs compared with 23.4% of FAs.",
            "output": [
                "Does follicular thyroid carcinoma but not adenoma recruit tumor-associated macrophages by releasing CCL15?"
            ]
        },
        {
            "id": "task847-f9428b9382034ead9d9d81c9a753fbc1",
            "input": "Hepatic osteodystrophy has been reported in patients with various chronic liver diseases, including liver cirrhosis. However, it has not been well investigated in patients with hepatitis B virus infection. The aim of this study was to investigate the association between hepatitis B surface antigen (HBsAg) seropositivity and bone mineral density (BMD) in a population representative of normal Koreans.', 'Subjects with both HBsAg and BMD levels examined during the 2008-2010 Korea National Health and Nutrition Examination Surveys were included. HBsAg-seropositive (+) subjects were compared with those who were HBsAg-seronegative (-). BMD was measured at the lumbar spine and femur by dual-energy X-ray absorptiometry. Multivariable logistic regression was performed for BMD .', 'In total, 11,306 participants were included in this study, among which 423 (3.7\\xa0%) were HBsAg(+): 153 premenopausal female (3.4\\xa0%), 83 postmenopausal female (3.5\\xa0%), and 187 male (4.2\\xa0%). Multivariable logistic regression analysis adjusted for age and body mass index showed that HBsAg(+) male had significantly lower BMD of the femoral neck than HBsAg(-) male (0.810\\xa0\u00b1\\xa00.009 vs. 0.827\\xa0\u00b1\\xa00.002\\xa0g/cm(2), p\\xa0=\\xa00.035). Further adjustment for waist circumference, smoking, drinking, exercise, income, occupation, and vitamin D levels showed that HBsAg(+) male had significantly lower BMD of the femur neck (0.810\\xa0\u00b1\\xa00.010 vs. 0.831\\xa0\u00b1\\xa00.002\\xa0g/cm(2), p\\xa0=\\xa00.032) and lumbar spine (0.953\\xa0\u00b1\\xa00.011 vs. 0.974\\xa0\u00b1\\xa00.003\\xa0g/cm(2), p\\xa0=\\xa00.049) than HBsAg(-) male.",
            "output": [
                "Are males seropositive for hepatitis B surface antigen at risk of lower bone mineral density : the 2008-2010 Korea National Health and Nutrition Examination Surveys?"
            ]
        },
        {
            "id": "task847-e3f48b85421044dbbad1a51618efd93f",
            "input": "To determine the antibiotic resistance patterns of pathogenic Escherichia coli on goat meat carcass at Huruma and Kiserian abattoirs in Kenya.', 'Laboratory based study.', 'Huruma and Kiserian abattoirs in Kenya,', '400 slaughtered goats inspected by veterinary health officers and approved for human consumption.', 'A Total of 400 slaughtered goats which were inspected by veterinary health officers and approved for human consumption were sampled from Huruma and Kiserian abattoir. Goat carcass swabs were collected by passing each swab tissue on four parts of the carcass mainly neck, right and left forelimbs, right and left hind limbs, and brisket.', 'A total of 54 E. coli isolates were isolated and confirmed to be pathogenic. The percentage of isolates resistant to various microbial agents was recorded as follows: ampicillin (26 %), amoxycillin-clavulanic acid (17%), tetracycline (15%), chroramphenicol (4%), and ceftrixone (2% each). All Escherichia coli isolates were susceptible to gentamicin sulphamethaxazole-trimethomprin, kanamycin, cetriazididine (CAZ, 30pg), ciproxacin, nalidixic acid and chloramphenicol. Isolates were resistant to one or more of the antibiotics tested. Among the drugs tested, resistance was more frequently observed against ampicillin, amoxycillin-clavulanic acid, tetracycline, ceftrixone and chroramphenicol antibiotics. Among the isolates 26(48%) were positive for the stx1 gene, 19(35%) had the eae gene, 10(19%) possessed est gene,while 8(15%) harboured elt gene. Overall five isolates (10%) possessed aspu gene and two (4%) had aggR gene. No isolate possessed ipah gene.",
            "output": [
                "Does mOLECULAR CHARACTERISATION AND ANTIMICROBIAL RESISTANCE PATTERNS OF ESCHERICHIA COLI isolate FROM GOATS SLAUGHTERED IN PARTS OF KENYA?"
            ]
        },
        {
            "id": "task847-a08ea9a7317849b3833038ed7b390252",
            "input": "Gastrointestinal (GI) symptoms of nausea, vomiting, and abdominal pain are common in patients with orthostatic intolerance (OI), including neurally mediated hypotension (NMH) and postural orthostatic tachycardia syndrome (POTS). Autonomic dysregulation is considered the underlying pathophysiology behind the cardiovascular symptoms of POTS. Because the autonomic nervous system also regulates GI motility, we hypothesized that patients with POTS and GI symptoms will have evidence of autonomic dysmotility of the upper GI tract.', 'Thirty-five subjects with OI and GI symptoms were studied. All the subjects had a 24-hour antroduodenal manometry (ADM) study, in conjunction with pharmacologic challenge and autonomic and tilt table testing (TTT).', 'The mean subject age was 16.2\\u200a\u00b1\\u200a2.8 years (range 10-23.8 years), and male to female ratio was 10:25. TTT was abnormal in all the 35 subjects, whereas Valsalva testing was abnormal (+40 mmHG) in 21 of 34 (62%) subjects, and corrected QT interval was \u22650.44 seconds in 19 of 35 (54%) subjects. During TTT, GI symptoms were reproduced in 31 of 35 (89%) studies. ADM was found to be abnormal at baseline, before the TTT in 5 of 35 (14%) subjects, whereas it became abnormal in 23 of 34 (68%) subjects during TTT. In addition, the expected response to the pharmacologic challenge was limited. Overall, ADM was abnormal in 26 of 35 (74%) patients either at baseline or during TTT in these subjects with OI.",
            "output": [
                "Does antroduodenal Manometry be Abnormal in Children Presenting With Orthostatic Intolerance and Gastrointestinal Symptoms?"
            ]
        },
        {
            "id": "task847-b00459b51a7f4856ace46488cc829606",
            "input": "Although right-sided diverticulitis is perceived to have a higher incidence among Asians and infrequently requires surgical management in comparison with sigmoid diverticulitis, it is unknown whether differences in outcomes are due to ethnic disparity or disease pathophysiology.', 'The aim of this study was to determine the surgical outcomes for Asian and non-Asian patients with diverticulitis who underwent colectomy.', 'Patients identifiable by ethnicity in the Nationwide Inpatient Sample with diverticulitis and colectomy between 2004 and 2010 were included. Univariate comparisons were made between Asian and non-Asian patients by using t tests for continuous variables and \u03c7 tests for categorical variables. Propensity score matching analysis was performed to compare Asian patients with otherwise similar non-Asian patients.', 'Included were 58,142 non-Asian and 335 Asian patients with diverticulitis who underwent a colectomy.', 'The primary outcomes were in-hospital mortality, hospital length of stay, and total costs.', 'Asian patients were younger (56.1 vs. 59.2 years, p < 0.0001), were more likely to undergo a right colectomy (22.7% vs. 4.1%, p < 0.0001), and were more likely to have emergent/urgent surgery than the non-Asian patients (67.1% vs. 49.8%, p < 0.0001). Without controlling for patient/disease factors, there were statistically significant differences in mortality (non-Asian 2.2% vs. Asian 4.2%; p = 0.014), length of stay (non-Asian 8.9 vs. Asian 9.8 days; p = 0.0166), and costs (non-Asian $18,783 vs. Asian $21,901; p = 0.001). Propensity score matching comparing 333 non-Asian patients with 333 similar Asian patients showed that, whereas differences in cost and length of stay became insignificant, the difference in mortality remained statistically significant.",
            "output": [
                "Is higher Mortality in Surgically Managed Diverticulitis Associated with Asian Ethnicity and Right-Sided Disease?"
            ]
        },
        {
            "id": "task847-53d1e39caddc44b184757b81adaeabd1",
            "input": "Hepatitis C virus (HCV) is a major public health concern and data on its molecular epidemiology in Sweden is scarce. We carried out an 8-year population-based study of newly diagnosed HCV cases in one of Sweden's centrally situated counties, S\u00f6dermanland (D-county). The aim was to characterize the HCV strains circulating, analyze their genetic relatedness to detect networks, and in combination with demographic data learn more about transmission.\", 'Molecular analyses of serum samples from 91% (N=557) of all newly notified cases in D-county, 2002-2009, were performed. Phylogenetic analysis (NS5B gene, 300 bp) was linked to demographic data from the national surveillance database, SmiNet, to characterize D-county transmission clusters. The linear-by-linear association test (LBL) was used to analyze trends over time.', 'The most prevalent subtypes were 1a (38%) and 3a (34%). Subtype 1a was most prevalent among cases transmitted via sexual contact, via contaminated blood, or blood products, while subtype 3a was most prevalent among people who inject drugs (PWIDs). Phylogenetic analysis revealed that the subtype 3a sequences formed more and larger transmission clusters (50% of the sequences clustered), while the 1a sequences formed smaller clusters (19% of the sequences clustered), possibly suggesting different epidemics.",
            "output": [
                "Does molecular characterization of HCV in a Swedish county over 8 years ( 2002-2009 ) reveal distinct transmission patterns?"
            ]
        },
        {
            "id": "task847-b1f2efbb1c144e97a33fb9d8060362a6",
            "input": "Urothelial carcinoma associated 1 (UCA1) functions as an oncogene, which promotes cancer cell proliferation, invasion, and metastasis, and is responsible for drug resistance. This study aimed to determine the expression level of UCA1 in ovarian cancer and to further investigate its clinical significance.', 'The expression levels of UCA1 in ovarian cancer and normal ovaries were determined by quantitative real-time PCR. The relationship between UCA1 expression and clinical features and the prognostic value of UCA1 for overall survival were examined.', 'UCA1 expression in ovarian cancer tissues was significantly upregulated compared with normal ovarian tissues. High UCA1 expression was related to lymph node metastasis, FIGO stage, and response to chemotherapy. Kaplan-Meier analysis demonstrated that high UCA1 expression was associated with poorer overall survival in patients with ovarian cancer. Cox proportional hazards analysis showed that high UCA1 expression was an independent prognostic marker of poor outcome. This effect remained significant in the further stratification analysis.",
            "output": [
                "Does uCA1 overexpression predict clinical outcome of patients with ovarian cancer receiving adjuvant chemotherapy?"
            ]
        },
        {
            "id": "task847-3cc4163861ab426a9cdd5b90a288612c",
            "input": "The purpose of this study was to compare the effect of whole body vibration (WBV) and local muscle vibration (LMV) on quadriceps function.', 'Sixty adults were randomized to WBV, LMV, or control groups. Quadriceps function [Hoffmann (H)-reflex, active motor threshold (AMT), motor evoked potential (MEP) and electromyographic amplitude, peak torque (PT), rate of torque development (RTD), and central activation ratio (CAR)] was assessed before and immediately after and 10 and 20 minutes after interventions.', 'WBV improved PT, CAR, AMT, EMG, and MEP amplitude, and EMG amplitude and CAR were greater than control after application. LMV improved EMG amplitude and AMT, and EMG amplitude was greater than control after application. AMT remained lower 10 and 20 minutes after WBV and LMV. No differences were noted between LMV and WBV. Vibration did not influence H-reflex or RTD.",
            "output": [
                "Do immediate effect of vibratory stimuli on quadriceps function in healthy adults?"
            ]
        },
        {
            "id": "task847-445a51b3df0b4e619e5308143b6d52bf",
            "input": "The multisubunit SIN3 complex is a global transcriptional regulator. In Drosophila, a single Sin3A gene encodes different isoforms of SIN3, of which SIN3 187 and SIN3 220 are the major isoforms. Previous studies have demonstrated functional non-redundancy of SIN3 isoforms. The role of SIN3 isoforms in regulating distinct biological processes, however, is not well characterized.', 'We established a Drosophila S2 cell culture model system in which cells predominantly express either SIN3 187 or SIN3 220. To identify genomic targets of SIN3 isoforms, we performed chromatin immunoprecipitation followed by deep sequencing. Our data demonstrate that upon overexpression of SIN3 187, the level of SIN3 220 decreased and the large majority of genomic sites bound by SIN3 220 were instead bound by SIN3 187. We used RNA-seq to identify genes regulated by the expression of one isoform or the other. In S2 cells, which predominantly express SIN3 220, we found that SIN3 220 directly regulates genes involved in metabolism and cell proliferation. We also determined that SIN3 187 regulates a unique set of genes and likely modulates expression of many genes also regulated by SIN3 220. Interestingly, biological pathways enriched for genes specifically regulated by SIN3 187 strongly suggest that this isoform plays an important role during the transition from the embryonic to the larval stage of development.",
            "output": [
                "Do genome-wide studies reveal novel and distinct biological pathways regulated by SIN3 isoforms?"
            ]
        },
        {
            "id": "task847-f7ebb1a9cb564007823af3e0880e2865",
            "input": "Children and adults with the lysosomal storage diseases mucopolysaccharidosis (MPS) types I, II and VI live shortened lives permeated by chronic pain and physical disability. Current treatments do not alleviate these problems. Thus there is a critical need to understand the mechanism of chronic pain and disability in MPS in order to improve the way we treat patients. A potential target is inflammation.', 'We hypothesized that excessive inflammation mediated by the tumor necrosis factor-\u03b1 (TNF-\u03b1) inflammatory pathway is the fundamental cause of much of the chronic pain and physical disability in MPS.', \"55 patients with MPS I, II, or VI were enrolled over the course of a 5-year prospective longitudinal natural history study and evaluated annually for 2-5years. 51 healthy controls were enrolled in a separate cross-sectional study of bone and energy metabolism. TNF-\u03b1 was measured by ELISA. Pain and physical disability were measured by the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50). Differences in log-transformed TNF-\u03b1 levels and associations with CHQ domains were evaluated using a linear mixed effects model with random intercept.\", 'TNF-\u03b1 levels were measured in 48 MPS (age: 5-17years; 35% female) and 51 controls (age: 8-17years; 53% female). Among MPS, 22 (46%) were treated with hematopoietic cell transplantation (HCT) alone, 24 (50%) with enzyme replacement therapy (ERT) alone, and 2 (4%) with both HCT and ERT. TNF-\u03b1 levels are higher in MPS compared to healthy controls (p<0.001). Higher TNF-\u03b1 levels are associated with increased pain and decreased physical function, social limitations due to physical health, and physical summary score (all p<0.05). TNF-\u03b1 levels were not significantly associated with the general health score. TNF-\u03b1 levels did not change significantly over time in MPS.",
            "output": [
                "Is elevated TNF-\u03b1 associated with pain and physical disability in mucopolysaccharidosis types I , II , and VI?"
            ]
        },
        {
            "id": "task847-2ea08928dc834afa99618b0d2da81a05",
            "input": "The association between migraine and Parkinson's disease (PD) remains controversial. The purpose of the present population-based, propensity score-matched follow-up study was to investigate whether migraineurs are at a higher risk of developing PD.\", 'A total of 41,019 subjects aged between 40 and 90 years with at least two ambulatory visits with a diagnosis of migraine in 2001 were enrolled in the migraine group. A logistic regression model that included age, sex, pre-existing comorbidities and socioeconomic status as covariates was used to compute the propensity score. The non-migraine group consisted of 41,019 propensity score-matched, randomly sampled subjects without migraine. The PD-free survival rate were estimated using the Kaplan-Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of developing PD.', 'During follow-up, 148 subjects in the migraine group and 101 in the non-migraine group developed PD. Compared to the non-migraine group, the hazard ratio of PD for the migraine group was 1.64 (95% confidence interval: 1.25-2.14, p\\u2009=\\u20090.0004). The PD-free survival rate for the migraine group was significantly lower than that for the non-migraine group (p\\u2009=\\u20090.0041).",
            "output": [
                "Is migraine related to an increased risk of Parkinson 's disease : A population-based , propensity score-matched , longitudinal follow-up study?"
            ]
        },
        {
            "id": "task847-1366d750f178466bab600cf4fb6b9abd",
            "input": "Mutation rates are consistently varied in cancer genome and play an important role in tumorigenesis, however, little has been known about their function potential and impact on the distribution of functional mutations. In this study, we investigated genomic features which affect mutation pattern and the function importance of mutation pattern in cancer.', 'Somatic mutations of clear-cell renal cell carcinoma, liver cancer, lung cancer and melanoma and single nucleotide polymorphisms (SNPs) were intersected with 54 distinct genomic features. Somatic mutation and SNP densities were then computed for each feature type. We constructed 2856 1-Mb windows, in which each row (1-Mb window) contains somatic mutation, SNP densities and 54 feature vectors. Correlation analyses were conducted between somatic mutation, SNP densities and each feature vector. We also built two random forest models, namely somatic mutation model (CSM) and SNP model to predict somatic mutation and SNP densities on a 1-Kb scale. The relation of CSM and SNP scores was further analyzed with the distributions of deleterious coding variants predicted by SIFT and Mutation Assessor, non-coding functional variants evaluated with FunSeq 2 and GWAVA and disease-causing variants from HGMD and ClinVar databases.', 'We observed a wide range of genomic features which affect local mutation rates, such as replication time, transcription levels, histone marks and regulatory elements. Repressive histone marks, replication time and promoter contributed most to the CSM models, while, recombination rate and chromatin organizations were most important for the SNP model. We showed low mutated regions preferentially have higher densities of deleterious coding mutations, higher average scores of non-coding variants, higher fraction of functional regions and higher enrichment of disease-causing variants as compared to high mutated regions.",
            "output": [
                "Is mutation pattern an influential factor on functional mutation rates in cancer?"
            ]
        },
        {
            "id": "task847-34b23f3ed29e42dfa2cc08fd5c122361",
            "input": "Aggressive periodontitis is characterized by rapid destruction of periodontal tissue caused by Aggregatibacter actinomycetemcomitans. Interleukin (IL)-1\u03b2 is a proinflammatory cytokine, and its production is tightly regulated by inflammasome activation. Xylitol, an anticaries agent, is anti-inflammatory, but its effect on inflammasome activation has not been researched. This study investigates the effect of xylitol on inflammasome activation induced by A. actinomycetemcomitans.', 'The differentiated THP-1 macrophages were stimulated by A. actinomycetemcomitans with or without xylitol and the expressions of IL-1\u03b2 and inflammasome components were detected by real time PCR, ELISA, confocal microscopy and Immunoblot analysis. The effects of xylitol on the adhesion and invasion of A. actinomycetemcomitans to cells were measured by viable cell count.', 'A. actinomycetemcomitans increased pro IL-1\u03b2 synthesis and IL-1\u03b2 secretion in a multiplicity of infection- and time-dependent manner. A. actinomycetemcomitans also stimulated caspase-1 activation. Among inflammasome components, apoptosis-associated speck-like protein containing a CARD (ASC) and absent in melanoma 2 (AIM2) proteins were upregulated by A. actinomycetemcomitans infection. When cells were pretreated with xylitol, proIL-1\u03b2 and IL-1\u03b2 production by A. actinomycetemcomitans infection was significantly decreased. Xylitol also inhibited ASC and AIM2 proteins and formation of ASC puncta. Furthermore, xylitol suppressed internalization of A. actinomycetemcomitans into differentiated THP-1 macrophages without affecting viability of A. actinomycetemcomitans within cells.",
            "output": [
                "Does aggregatibacter actinomycetemcomitans-Induced AIM2 Inflammasome Activation be Suppressed by Xylitol in Differentiated THP-1 Macrophages?"
            ]
        },
        {
            "id": "task847-e60bba26e4c04a27a1a1c653c869133a",
            "input": "Hypertrophic cardiomyopathy (HCM) patients are at risk of ventricular arrhythmias (VAs). We aimed to explore whether systolic function by strain echocardiography is related to VAs and to the extent of fibrosis by cardiac magnetic resonance imaging (CMR).', 'We included 150 HCM patients and 50 healthy individuals. VAs were defined as non-sustained and sustained ventricular tachycardia and aborted cardiac arrest. Left ventricular function was assessed by ejection fraction (EF) and by global longitudinal strain (GLS) assessed by speckle tracking echocardiography. Mechanical dispersion was calculated as standard deviation (SD) of time from Q/R on ECG to peak longitudinal strain in 16 left ventricular segments. Late gadolinium enhancement (LGE) was assessed by CMR. HCM patients had similar EF (61 \u00b1 5% vs. 61 \u00b1 8%, P = 0.77), but worse GLS (-15.7 \u00b1 3.6% vs. -21.1 \u00b1 1.9%, P < 0.001) and more pronounced mechanical dispersion (64 \u00b1 22 vs. 36 \u00b1 13 ms, P < 0.001) compared with healthy individuals. VAs were documented in 37 (25%) HCM patients. Patients with VAs had worse GLS (-14.1 \u00b1 3.6% vs. -16.3 \u00b1 3.4%, P < 0.01), more pronounced mechanical dispersion (79 \u00b1 27 vs. 59 \u00b1 16 ms, P < 0.001), and higher %LGE (6.1 \u00b1 7.8% vs. 0.5 \u00b1 1.4%, P < 0.001) than patients without VAs. Mechanical dispersion correlated with %LGE (R = 0.52, P < 0.001) and was independently associated with VAs (OR 1.6, 95% CI 1.1-2.3, P = 0.02) and improved risk stratification for VAs.",
            "output": [
                "Is strain echocardiography related to fibrosis and ventricular arrhythmias in hypertrophic cardiomyopathy?"
            ]
        },
        {
            "id": "task847-6497162b3d684a059716750d3f5bb40a",
            "input": "Using publicly available data from inbred mouse strains, we conducted a genome-wide association study to identify loci that accounted for liver-related phenotypes between C57BL/6J and A/J mice fed a Paigen diet. We confirmed genome-wide significant associations for hepatic cholesterol (chromosome 10A2) and serum total bile acid concentration (chromosome 12E) and identified a new locus for liver inflammation (chromosome 7C). Analysis of consomic mice confirmed that chromosome 12 A/J alleles accounted for the variance in serum total bile acid concentrations and had pleiotropic effects on liver mass, serum cholesterol, and serum alanine aminotransferase activity. Using an affected-only haplotype analysis among strains, we refined the chromosome 12E signal to a 1.95 Mb linkage disequilibrium block containing only one gene, sel-1 suppressor of lin-12-like (Sel1l). RNA sequencing and immunoblotting demonstrated that the risk allele locally conferred reduced expression of SEL1L in liver and distantly down-regulated pathways associated with hepatocyte nuclear factor 1 homeobox A (Hnf1a) and hepatocyte nuclear factor 4A (Hnf4a), known modifiers of bile acid transporters and metabolic traits. Consistent with these data, knockdown of SEL1L in HepG2 cells resulted in reduced HNF1A and HNF4A and increased bile acids in culture media; it further captured multiple molecular signatures observed in consomic mouse livers with reduced SEL1L. Finally, dogs harboring a SEL1L mutation and Sel1l(+/-) mice fed a Paigen diet had significantly increased serum total bile acid concentrations, providing independent confirmation linking SEL1L to bile acid metabolism.",
            "output": [
                "Does genome-wide association study in mice identify loci affecting liver-related phenotypes including Sel1l influencing serum bile acids?"
            ]
        },
        {
            "id": "task847-e841d211b17a4deaa8abd0cbcf40af09",
            "input": "Accelerated thrombus formation induced by exposure to combustion-derived air pollution has been linked to alterations in endogenous fibrinolysis and platelet activation in response to pulmonary and systemic inflammation. We hypothesised that mechanisms independent of inflammation contribute to accelerated thrombus formation following exposure to diesel exhaust particles (DEP).', 'Thrombosis in rats was assessed 2, 6 and 24 h after administration of DEP, carbon black (CB; control carbon nanoparticle), DQ12 quartz microparticles (to induce pulmonary inflammation) or saline (vehicle) by either intra-tracheal instillation (0.5 mg, except Quartz; 0.125 mg) or intravenous injection (0.5 mg/kg). Thrombogenicity was assessed by carotid artery occlusion, fibrinolytic variables and platelet-monocyte aggregates. Measures of inflammation were determined in plasma and bronchoalveolar lavage fluid. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)-1 were measured following direct in vitro exposure of human umbilical vein endothelial cells (HUVECs) to DEP (10-150 \u03bcg/mL).', 'Instillation of DEP reduced the time to thrombotic occlusion in vivo, coinciding with the peak of DEP-induced pulmonary inflammation (6 h). CB and DQ12 produced greater inflammation than DEP but did not alter time to thrombotic occlusion. Intravenous DEP produced an earlier (2 h) acceleration of thrombosis (as did CB) without pulmonary or systemic inflammation. DEP inhibited t-PA and PAI-1 release from HUVECs, and reduced the t-PA/PAI-1 ratio in vivo; similar effects in vivo were seen with CB and DQ12. DEP, but not CB or DQ12, increased platelet-monocyte aggregates.",
            "output": [
                "Does platelet activation independent of pulmonary inflammation contribute to diesel exhaust particulate-induced promotion of arterial thrombosis?"
            ]
        },
        {
            "id": "task847-08525f84ea534352aef11f91bf3b1307",
            "input": "GaAlAs lasers induce pulp mineralization by promoting reparative dentinogenesis. This study analyzed the expression of dentin matrix protein 1 (DMP1) and osteopontin in GaAlAs laser-irradiated rat molars, to examine the hypothesis that these proteins play a role in the laser-induced reparative dentinogenic process.', 'The mesial surfaces of the upper first molars of 8-week-old Wistar rats were irradiated with a pulsed GaAlAs laser. After 1-14\\xa0days, mRNA expression of DMP1 and osteopontin in the coronal pulp was analyzed using real-time PCR. DMP1, osteopontin, and heat shock protein 25 (HSP25) were immunolocalized at 1-21\\xa0days.', 'The pulp exhibited a degenerative zone in its mesial portion on days 1-3, and progressive formation of reparative dentin lined with HSP25-immunoreactive odontoblast-like cells, from day 7 onwards. DMP1 and osteopontin mRNA expression were significantly upregulated on days 1-7 and 3-7, respectively. From day 7 onwards, DMP1 and osteopontin immunoreactivity colocalized along the boundary between the primary and reparative dentin.",
            "output": [
                "Does gaAlAs laser-induced pulp mineralization involve dentin matrix protein 1 and osteopontin expression?"
            ]
        },
        {
            "id": "task847-6353d2423f2a45a3b41bf8e451e2be3e",
            "input": "Caffeine is a commonly used drug for apnea of prematurity. It may, however, also have a beneficial effect on bronchopulmonary dysplasia (BPD), which is the most common complication of extreme preterm birth.', 'To study the inflammatory, structural and functional effects of caffeine in an animal model of BPD.', 'Preterm New Zealand-Dendermonde rabbits (gestational day 28; term 31) were randomized to three groups: normoxia-placebo (N-P), hyperoxia-placebo (H-P) and hyperoxia-caffeine (H-C). Lung function was assessed on postnatal day 5, along with airway morphometry, vascular morphometry and a score observing airway inflammation.', 'Caffeine improved lung function by increasing lung volume [mean displaced volume N-P: 40.1 \u00b1 6 ml/kg, H-P: 27.8 \u00b1 8 ml/kg and H-C: 34.4 \u00b1 7 ml/kg (p < 0.05); total lung capacity: N-P: 1.17 \u00b1 0.1 ml, H-P: 0.67 \u00b1 0.1 ml and H-C: 1.1 \u00b1 0.1 ml (p < 0.05)], decreasing tissue damping [N-P: 2.7 \u00b1 0.3 cm H2O/ml, H-P: 4.6 \u00b1 0.6 cm H2O/ml and H-C: 3.2 \u00b1 0.4 cm H2O/ml (p < 0.05)], elastance [N-P: 9.3 \u00b1 2.4 cm H2O/ml, H-P: 19.2 \u00b1 7.4 cm H2O/ml and H-C: 10.7 \u00b1 2 cm H2O/ml (p < 0.05)] and compliance [N-P: 0.06 \u00b1 0.01 cm H2O/ml, H-P: 0.054 \u00b1 0.01 cm H2O/ml and H-C: 0.07 \u00b1 0.013 cm H2O/ml (p < 0.05)]. Caffeine also improved histology by decreasing alveolar size [linear intercepts; N-P: 83.6 \u00b1 1.7, H-P: 82.9 \u00b1 1.6 and H-C: 67.3 \u00b1 1.4 (p < 0.05)], increasing radial alveolar count (N-P: 6.6 \u00b1 0.5, H-P: 5.7 \u00b1 0.6 and H-C: 7.05 \u00b1 0.5) and decreasing the acute inflammation score [N-P: 0.3 \u00b1 0.1, H-P: 0.5 \u00b1 0.1 and H-C: 0.4 \u00b1 0.1 (p < 0.05)].",
            "output": [
                "Does caffeine prevent Hyperoxia-Induced Functional and Structural Lung Damage in Preterm Rabbits?"
            ]
        },
        {
            "id": "task847-58395462d8684e399c3b2f336d279659",
            "input": "Diffusion time (\u0394) effect in diffusion measurements has been validated as a sensitive biomarker in liver fibrosis by rat models. To extend this finding to clinical study, a reliable imaging technique is highly desirable. This study aimed to develop an optimal stimulated echo acquisition mode (STEAM) diffusion-weighted imaging (DWI) method dedicated to human liver imaging on 3 Tesla (T) and preliminarily investigate the dependence effect in healthy volunteers.', 'STEAM DWI with single-shot echo planar imaging readout was used as it provided better signal-to-noise ratio (SNR) than spin echo DWI methods when a long \u0394 was needed for liver imaging. Additionally, a slice-selection gradient reversal method was used for fat suppression. Motion compensation and SNR improvement strategies were used to further improve the image quality. Five b-values with three \u0394s were tested in 10 volunteers.', 'Effective fat suppression and motion compensation were reproducibly achieved in the optimized sequence. The signal decay generally became slower when the \u0394s increased. Obvious reduction of diffusion coefficients was observed with increasing \u0394s in the liver.",
            "output": [
                "Do stimulated echo diffusion weighted imaging of the liver at 3 Tesla?"
            ]
        },
        {
            "id": "task847-ed983aa248834f558af7728ce7b5b72d",
            "input": "Nailfold videocapillaroscopy (NVC) identifies the microvascular hallmarks of systemic sclerosis (SSc) and vascular endothelial growth factor (VEGF) and may play a pivotal role in the associated vasculopathy. The aim of the present study was to compare NVC alterations with clinical subsets, internal organ involvement, and serum VEGF levels in a cohort of selected SSc cases.', 'We studied 44 patients with SSc who were evaluated within 3\\xa0months from enrollment by NVC, skin score, severity index, pulmonary function tests, carbon monoxide diffusing capacity (DLCO), echocardiography, pulmonary high-resolution computed tomography (HRCT), gastroesophageal (GE) endoscopy or manometry or X-ray, and serum autoantibodies. Serum VEGF-A levels were determined by ELISA in 72 SSc patients and 31 healthy controls.', 'Giant capillaries were inversely correlated with age (p\\xa0=\\xa00.034, r\\xa0=\\xa0-0.34) and to the extent of reticular pattern at HRCT (p\\xa0=\\xa00.04, r\\xa0=\\xa0-0.5). Avascular areas were directly correlated with capillaroscopy skin ulcer risk index (CSURI) (p\\xa0=\\xa00.006, r\\xa0=\\xa0+0.4) and severity index (p\\xa0=\\xa00.004, r\\xa0=\\xa0+0.5). The mean capillary density was directly correlated to the ulcer number (p\\xa0=\\xa00.02, r\\xa0=\\xa0+0.4) and to DLCO/alveolar volume (p\\xa0=\\xa00.02, r\\xa0=\\xa0+0.4) and inversely correlated with severity index (p\\xa0=\\xa00.01, r\\xa0=\\xa0-0.4) and skin score (p\\xa0=\\xa00.02, r\\xa0=\\xa0-0.4). Serum VEGF levels were higher in the SSc population vs controls (p\\xa0=\\xa00.03) and inversely correlated with DLCO (p\\xa0=\\xa00.01, r\\xa0=-0.4) and directly with ground-glass and reticular pattern at HRCT (p\\xa0=\\xa00.04, r\\xa0=\\xa0+0.4 for both).",
            "output": [
                "Are nailfold videocapillaroscopy and serum VEGF levels in scleroderma associated with internal organ involvement?"
            ]
        },
        {
            "id": "task847-10047266db9c43489c9f4f3232b1d5bc",
            "input": "ANGPTL8 (betatrophin) has been recently identified as a regulator of lipid metabolism through its interaction with ANGPTL3. A sequence variant in ANGPTL8 has been shown to associate with lower level of Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL). The objective of this study is to identify sequence variants in ANGPTL8 gene in Arabs and investigate their association with ANGPTL8 plasma level and clinical parameters.', 'A cross sectional study was designed to examine the level of ANGPTL8 in 283 non-diabetic Arabs, and to identify its sequence variants using Sanger sequencing and their association with various clinical parameters.', 'Using Sanger sequencing, we sequenced the full ANGPTL8 gene in 283 Arabs identifying two single nucleotide polymorphisms (SNPs) Rs.892066 and Rs.2278426 in the coding region. Our data shows for the first time that Arabs with the heterozygote form of (c.194C > T Rs.2278426) had higher level of Fasting Blood Glucose (FBG) compared to the CC homozygotes. LDL and HDL level in these subjects did not show significant difference between the two subgroups. Circulation level of ANGPTL8 did not vary between the two forms. No significant changes were observed between the various forms of Rs.892066 variant and FBG, LDL or HDL.",
            "output": [
                "Is aNGPTL8/Betatrophin R59W variant associated with higher glucose level in non-diabetic Arabs living in Kuwaits?"
            ]
        },
        {
            "id": "task847-627df43999834d968db42380d5d07139",
            "input": "To explore whether the prevalence and severity of retinopathy differ in diabetes cohorts diagnosed through screening as compared with conventional health care.', 'A total of 257 diabetes patients, 151 detected through screening and 106 through conventional clinical care, were included. Retinopathy was evaluated by fundus photography. The modified Airlie House adaptation of the Early Treatment Retinopathy Study protocol was used to grade the photographs. Averages of clinically collected fasting blood glucose (FBG), blood pressure and body mass index values were compiled from diabetes diagnosis until the eye examination. Blood chemistry, smoking habits and peripheral neuropathy were assessed at the time of the eye examination.', \"Among the screening-detected patients, 22% had retinopathy as compared to 51% among those clinically detected (p < 0.0001). In a multivariate analysis, patients with retinopathy were more likely to have increased average FBG (OR 1.42, 95% CI 1.19-1.70 per mmol/l) and peripheral neuropathy (OR 2.75, 95% CI 1.40-5.43), but less likely to have screening-detected diabetes (OR 0.31, 95% CI 0.17-0.57). Similar results were found using increasing severity grade of retinopathy as outcome. The cumulative retinopathy prevalence for the screening-detected diabetes cohort as compared with the clinically diagnosed cohort was significantly lower from 10 years' follow-up and onwards (p = 0.0002).",
            "output": [
                "Are early detection of type 2 diabetes mellitus and screening for retinopathy associated with reduced prevalence and severity of retinopathy?"
            ]
        },
        {
            "id": "task847-8023f714df8c4e2b938e2b6bb848ba95",
            "input": "Although animal studies demonstrated that Smad7 induction ameliorates TGF-\u03b2/SMAD-mediated fibrogenesis, its role in human hepatic diseases is rather obscure. Our study explored the activation status of TGF-\u03b2/activin pathway in patients with chronic liver diseases, and how it is affected by successful antiviral treatment in chronic HBV hepatitis (CHB).', 'Thirty-seven CHB patients (19 with active disease, 14 completely remitted on long-term antiviral treatment and 4 with relapse after treatment withdrawal), 18 patients with chronic HCV hepatitis, 12 with non-alcoholic fatty liver disease (NAFLD), and 3 controls were enrolled in the study. Liver mRNA levels of CTGF, all TGF-\u03b2/activin isoforms, their receptors and intracellular mediators (SMADs) were evaluated using qRT-PCR and were correlated with the grade of liver inflammation and fibrosis staging. The expression and localization of pSMAD2 and pSMAD3 were assessed by immunohistochemistry.', 'TGF-\u03b2 signalling is activated in CHB patients with active disease, while SMAD7 is up-regulated during the resolution of inflammation after successful treatment. SMAD7 overexpression was also observed in NAFLD patients exhibiting no or minimal fibrosis, despite the activation of TGF-\u03b2/activin signaling.",
            "output": [
                "Is tGF-\u03b2 signaling activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment?"
            ]
        },
        {
            "id": "task847-17b7a2db536f4dcba094e5010af1baf1",
            "input": "Is the proteolytic activity of pregnancy-associated plasma protein-A (PAPP-A) regulated by the stanniocalcins (STC1 and STC2) during human follicle maturation?",
            "output": [
                "Is the proteolytic activity of pregnancy-associated plasma protein-A potentially regulated by stanniocalcin-1 and -2 during human ovarian follicle development?"
            ]
        },
        {
            "id": "task847-649bec67d13b426daa70ffce0968bf81",
            "input": "Several transport alterations have been described in intestinal inflammatory diseases. This is relevant because the primary function of the intestine is nutrient and mineral absorption. However, analysis of the transportome as a whole and the effect of commensal bacteria on it have not been addressed so far.', \"Five healthy and 6 Crohn's disease (CD) samples were hybridized to human HT-12 V4 Illumina GeneChip. Results were validated by reverse transcription-polymerase chain reaction (RT-PCR) analysis and with additional array data. Organ culture assays were performed from mucosa ileal wall specimens collected at surgery. Samples were incubated with or without commensal bacteria for 4 hours. Finally, RNA was isolated for microarray processing.\", 'The analysis of CD versus healthy ileal mucosa demonstrated upregulation of previously described genes involved in immunity and the inflammatory response in this disease. Interestingly, whole transcriptional analysis revealed profound alterations in the transportome profile. Sixty-two solute carrier (SLC) transporters displayed different expression patterns, most of them being downregulated. Changes were confirmed by RT-PCR in a randomly chosen subset of SLCs. A large number of amino acid transporters and most members of the enteric purinome were found to be altered. Most of these proteins were found at the apical membrane of the enterocyte, which could impair both amino acid absorption and purinergic signalling. Treatment of ileum specimen explants with commensal bacteria restored almost all CD transportome alterations.",
            "output": [
                "Does transportome Profiling identify Profound Alterations in Crohn 's Disease Partially Restored by Commensal Bacteria?"
            ]
        },
        {
            "id": "task847-24da01bc07ca4529804d9487339d247e",
            "input": "Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment.', 'Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7\\u2005days post-op.', 'Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment.",
            "output": [
                "Does implantation of healthy matrix-embedded endothelial cells rescue dysfunctional endothelium and ischaemic tissue in liver engraftment?"
            ]
        },
        {
            "id": "task847-7a76d52e690248f2ada2526d44bc3815",
            "input": "The fetal programming hypothesis suggests that intrauterine stimuli can induce metabolic changes in offspring, increasing the disease risk in adulthood. Periodontal disease may enhance serum cytokine levels. Cytokines such as tumor necrosis factor-alpha (TNF-\u03b1) have been associated with reduced glucose transporter type 4 (GLUT4) expression, decreased protein kinase B (Akt) phosphorylation, and insulin resistance. This study aimed to evaluate GLUT4 content, and Akt serine phosphorylation status in the gastrocnemius skeletal muscle (GSM), glycemia, insulinemia and change in body weight in offspring of rats with periodontal disease.', 'Female Wistar rats were distributed into a control group (CN) and an experimental periodontal disease group (PD), in which a ligature was placed around the mandibular first molars. Seven days after ligature placement, both groups were mated with normal male rats. The ligatures remained throughout pregnancy until weaning, after which the male offspring were distributed into groups: CN-o, control rat offspring; and PD-o, periodontal disease rat offspring. The body weight from 0 to 75days of age was measured. At 75days, the glycemia, insulinemia, TNF-\u03b1 levels, Akt serine phosphorylation, and GLUT4 content in the GSM were measured in the offspring.', 'The PD-o group showed a low birth weight (LBW), unchanged glycemia, increased insulinemia, insulin resistance, increased TNF-\u03b1 levels, decreased Akt serine phosphorylation status, and reduced GLUT4 content in the plasma membrane and translocation index after insulin stimulation.",
            "output": [
                "Does maternal periodontitis decrease plasma membrane GLUT4 content in skeletal muscle of adult offspring?"
            ]
        },
        {
            "id": "task847-6ad353262c1c44e9bbfcf8724a10daf3",
            "input": "The association between human papillomavirus (HPV) infections and cervical cancer has suggested the design of prophylactic and therapeutic vaccines against genital warts. The HPV capsid has made of two L1 and L2 coat proteins that have produced late in viral infections. Regarding to the recent studies, two commercial prophylactic vaccines have based on L1 viral like particles (VLPs) could strongly induce antibody responses, and protect human body from HPV infections. However, the use of these HPV vaccines has hindered due to their high cost and some limitations. Currently, among various vaccination strategies, live vector-based vaccines have attracted a great attention.', 'Herein, a non-pathogenic strain of the protozoan organism known as Leishmania tarentolae has utilized to induce potent humoral immunity in mice model.', 'At first, cloning of HPV16 L1 gene into Leishmania expression vector has performed and confirmed by PCR and digestion with restriction enzymes. The promastigotes of Leishmania tarentolae (L.tar) have transfected with linearized DNA construct by electroporation. Protein expression has analyzed by SDS-PAGE and western blotting. Then, the immunogenicity of leishmania expressing L1 protein (L.tar-L1) has assessed in mice model.', 'Our data has indicated that subcutaneous immunization of mice with the recombinant L.tar-L1 has led to enhance the levels of IgG1 and lgG2a in comparison with control groups. Furthermore, there was no significant increase in antibody levels between two and three times of immunizations.",
            "output": [
                "Does a Live Vector Expressing HPV16 L1 generate an Adjuvant-Induced Antibody Response In-vivo?"
            ]
        },
        {
            "id": "task847-86c8a13a49064bf3a1eb5f1d375145dd",
            "input": "Specific monocyte and macrophage subsets have been implicated in atherosclerosis, with intermediate monocytes proportionally elevated in cardiovascular disease and M1 macrophages abundant in unstable atherosclerotic plaques. While several studies have shown altered proportions of these subsets in atherosclerosis, studies examining functional and phenotypic subset alterations remain scarce.', 'We used whole blood flow cytometry to investigate the expression of M1 (CD86) and M2 (CD163) markers on monocyte subsets of atherosclerotic patients and controls.', 'Atherosclerotic patients had a more inflammatory monocyte profile than controls, indicated by increased intermediate subset proportions, a higher classical monocyte CD86/CD163 ratio, and elevated serum M1-related chemokines. A more inflammatory profile appeared to correlate with atherosclerotic risk, as in controls classical monocyte CD86/CD163 ratio was negatively correlated with HDL and apolipoprotein A1, and positively correlated with Interleukin-1\u03b2.",
            "output": [
                "Do human classical monocytes display unbalanced M1/M2 phenotype with increased atherosclerotic risk and presence of disease?"
            ]
        },
        {
            "id": "task847-ef44d89e8a5d430ca420d27570bb5976",
            "input": "To investigate the relationship between the damages of hand functions and the type of cerebral palsy (CP) in children with CP.', 'A total of 280 children aged 4-12 years old with CP in the 20 districts of Chengdu were included. The damages of hand functions were assessed with the Chinese Version of Manual Ability Classification System (MACS) and its relationship with the type of CP were analyzed.', 'Among the 280 investigated children, there were 195 chidren with spastic CP, which accounted for the largest proportion (69.64%), wherein the spastic diplegia was most common (56.41%). The classification of MACS was level I-II in 65.13% children with spastic CP, whereas the classification of MACS was level IU-V in 84. 44% and 80.95% children with mixed and dyskinetic CP, respectively. With the increase of the degree of cognitive dysfunction in children with CP, the level of MACS was also increased. There was a difference between the classification of MACS and the different type of CP (P<0.05). The children with spastic CP were mostly mild hand dysfunction, while the children with mixed and dyskinetic type of CP were mostly middle and severe hand dysfunction. A positive correlation was found between the MACS and the subtype of spastic CP (r=0.541, P<0.05). In most of the children with diplegia from spastic CP, the hand dysfunction was mild, whereas the children with quadriplegia from spastic CP were mostly middle and severe hand dysfunction.",
            "output": [
                "Do [ The Relationship Between the Damages of Hand Functions and the Type of Cerebral Palsy in Children ]?"
            ]
        },
        {
            "id": "task847-3e3e9b205c4d488fb870eab9787dfb57",
            "input": "The higher expression of vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) is associated with the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Fetuin-A is shown to have proangiogenic and proinflammatory effects.', 'This study included 245 T2DM patients consisting of 95 cases with non-diabetic retinopathy (NDR), 78 cases with non-proliferative diabetic retinopathy (NPDR) and 72 cases with proliferative diabetic retinopathy (PDR), in addition to 65 healthy controls. Serum fetuin-A, VEGF and CRP concentrations and related parameters were measured.', 'Significant positive correlations were found between fetuin-A and VEGF and CRP, and between VEGF and CRP in T2DM patients (all p<0.001). After adjustment for confounders, fetuin-A was correlated independently with VEGF and CRP in NPDR and PDR patients, but not in NDR subjects. In addition, fetuin-A was correlated independently with HOMA-IR (all 4 groups), HbA1c (NDR, NPDR and PDR groups) and duration of diabetes (PDR group). When compared with NDR and control subjects, NPDR and PDR patients had higher HOMA-IR.",
            "output": [
                "Are serum fetuin-A levels independently correlated with vascular endothelial growth factor and C-reactive protein concentrations in type 2 diabetic patients with diabetic retinopathy?"
            ]
        },
        {
            "id": "task847-a297c2431dec4a539d61abf6d0b99c7b",
            "input": "CTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients.', 'Blood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements.', 'CTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p = 0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases.",
            "output": [
                "Is arterial Blood , Rather Than Venous Blood , a Better Source for Circulating Melanoma Cells?"
            ]
        },
        {
            "id": "task847-07173432aa7f41139068847e033f6260",
            "input": "Walking economy declines with increasing age, possibly leading to mobility limitation in older adults. Multicomponent fitness training could delay the decline in walking economy.', 'This study aimed to determine the effect of multicomponent fitness training on walking economy in older adults.', 'Participants were untrained adults, age 50 to 83 yr (N = 26, 10 males, age = 63 \u00b1 6 yr, BMI = 25.6 \u00b1 2.1 kg\u00b7m, mean \u00b1 SD). A control group was also recruited (N = 16, 9 males, age = 66 \u00b1 10 yr, BMI = 25.4 \u00b1 3.0 kg\u00b7m), matching the intervention group for age, weight, body composition, and fitness. The intervention group followed a multicomponent fitness program of 1 h, twice per week during 1 yr. The control group did not take part in any physical training. Fat-free mass, walking economy, and maximal oxygen uptake (V\u02d9O2max) were measured in both groups before and after the year. Walking economy was measured with indirect calorimetry as the lowest energy needed to displace 1 kg of body mass for 1 m while walking on a treadmill. The data were compared between the two groups with repeated-measures ANOVA.', 'Thirty-two subjects completed all measurements. There was an interaction between the effects of time and group on V\u02d9O2max (P < 0.05) and walking economy (P < 0.05), whereas fat-free mass did not change significantly (P = 0.06). V\u02d9O2max decreased by 1.8 mL\u00b7kg\u00b7min in the control group and increased by 1.3 mL\u00b7kg\u00b7min in the intervention group. The lowest energy needed to walk increased by 0.12 J\u00b7kg\u00b7m in the control group and decreased in the intervention group by 0.13 J\u00b7kg\u00b7m.",
            "output": [
                "Does multicomponent Fitness Training improve Walking Economy in Older Adults?"
            ]
        },
        {
            "id": "task847-f3ea1fc03a8c4987ab6cfdf838fb1003",
            "input": "The presence of perianal disease in Crohn's disease patients is one of the factors of postoperative recurrence. The aim of this study is to evaluate long-term prognosis of perianal Crohn's disease patients in Asian.\", \"Patients with Crohn's disease who had undergone surgical bowel resection were divided into two groups according to the presence of perianal lesion. We monitored the occurrences of abdominal and/or perianal reoperation and readmission due to disease flare-up.\", 'The 132 patients included in the study were divided into 2 groups, those with perianal disease (45 patients, 34.1%) and those without perianal disease (87 patients, 65.9%). Patients with perianal disease was younger in age (33.8 years versus 39.8 years, p = 0.015) and had been diagnosed as CD at a younger age (21.9 years versus 28.6 years, p = 0.005) than patients without perianal disease. Patients with perianal disease showed more extra-intestinal manifestation than patients without perianal disease (8 versus 3, p = 0.008). Reoperation was required in 46 (44.8%) patients during the follow-up period. The presence of perianal disease independently increased the risk of reoperation [hazard ratio (HR), 3.112; confidence interval (CI), 1.707-5.675]. Furthermore, patients with perianal disease had increasing risks of abdominal reoperation (HR 1.978; 95% CI, 1.034-3.784).",
            "output": [
                "Do patients with perianal Crohn 's disease have poor disease outcomes after primary bowel resection?"
            ]
        },
        {
            "id": "task847-05cf50d1425d434ea45f4a841db17616",
            "input": "Sub-lethal doses of ionizing radiation (IR) can alter the phenotype of target tissue by modulating genes that influence effector T cell activity. Previous studies indicate that cancer cells respond to radiation by up-regulating surface expression of death receptors, cell adhesion molecules and tumor-associated antigens (TAA). However, there is limited information available regarding how T cells themselves are altered following these interactions with irradiated tumor cells.', 'Here, several human colorectal tumor cell lines were exposed to radiation (0-10\\xa0Gy) in vitro and changes in the expression of molecules costimulatory to effector T cells (4-1BBL, OX-40L, CD70, ICOSL) were examined by flow cytometry. T cell effector function was assessed to determine if changes in these proteins were directly related to the changes in T cell function.', 'We found OX-40L and 4-1BBL to be the most consistently upregulated proteins on the surface of colorectal tumor cells post-IR while ICOSL and CD70 remained largely unaltered. Expression of these gene products correlated with enhanced killing of irradiated human colorectal tumor cells by TAA-specific T-cells. Importantly, blocking of both OX-40L and 4-1BBL reversed radiation-enhanced T-cell killing of human tumor targets as well as T-cell survival and activation.",
            "output": [
                "Is effector function of CTLs increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade?"
            ]
        },
        {
            "id": "task847-ca92ba279c034d5e8b63ca3f75d3214d",
            "input": "Sleep is defined as a reversible state of reduction in sensory responsiveness and immobility. A long-standing hypothesis suggests that a high arousal threshold during non-rapid eye movement (NREM) sleep is mediated by sleep spindle oscillations, impairing thalamocortical transmission of incoming sensory stimuli. Here we set out to test this idea directly by examining sensory-evoked neuronal spiking activity during natural sleep.', 'We compared neuronal (n = 269) and multiunit activity (MUA), as well as local field potentials (LFP) in rat core auditory cortex (A1) during NREM sleep, comparing responses to sounds depending on the presence or absence of sleep spindles.', 'We found that sleep spindles robustly modulated the timing of neuronal discharges in A1. However, responses to sounds were nearly identical for all measured signals including isolated neurons, MUA, and LFPs (all differences < 10%). Furthermore, in 10% of trials, auditory stimulation led to an early termination of the sleep spindle oscillation around 150-250 msec following stimulus onset. Finally, active ON states and inactive OFF periods during slow waves in NREM sleep affected the auditory response in opposite ways, depending on stimulus intensity.",
            "output": [
                "Are responses in Rat Core Auditory Cortex Preserved during Sleep Spindle Oscillations?"
            ]
        },
        {
            "id": "task847-4433b770bbec4bc7a73b29a1b185352c",
            "input": "To investigate how the effects of targeted memory reactivation (TMR) are influenced by memory accuracy prior to sleep and the presence or absence of direct cue-memory associations.', '30 participants associated each of 50 pictures with an unrelated word and then with a screen location in two separate tasks. During picture-location training, each picture was also presented with a semantically related sound. The sounds were therefore directly associated with the picture locations but indirectly associated with the words. During a subsequent nap, half of the sounds were replayed in slow wave sleep (SWS). The effect of TMR on memory for the picture locations (direct cue-memory associations) and picture-word pairs (indirect cue-memory associations) was then examined.', 'TMR reduced overall memory decay for recall of picture locations. Further analyses revealed a benefit of TMR for picture locations recalled with a low degree of accuracy prior to sleep, but not those recalled with a high degree of accuracy. The benefit of TMR for low accuracy memories was predicted by time spent in SWS. There was no benefit of TMR for memory of the picture-word pairs, irrespective of memory accuracy prior to sleep.",
            "output": [
                "Are the Benefits of Targeted Memory Reactivation for Consolidation in Sleep Contingent on Memory Accuracy and Direct Cue-Memory Associations?"
            ]
        },
        {
            "id": "task847-90f0b6af0d134e49806bd0cdbbf48e74",
            "input": "To assess whether intratumoral heterogeneity measured by (18)F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC).', 'We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment (18)F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher-order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2\\xa0years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models.', 'The best imaging biomarker for overall survival prediction was first-order entropy (AUC\\u2009=\\u20090.720), followed by TLG (AUC\\u2009=\\u20090.697), MTV (AUC\\u2009=\\u20090.692), and maximum SUV (AUC\\u2009=\\u20090.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P\\u2009=\\u20090.028) was independently associated with worse survival, whereas TLG (HR 0.98; P\\u2009=\\u20090.875) was not an independent prognostic factor.",
            "output": [
                "Does intratumoral heterogeneity of ( 18 ) F-FDG uptake predict survival in patients with pancreatic ductal adenocarcinoma?"
            ]
        },
        {
            "id": "task847-e4acfee415d747049dca18e98ae902b7",
            "input": "Coordinated muscle synergies in the human upper limb are controlled, in part, by a neural distribution network located in the cervical spinal cord, known as the cervical propriospinal system. Studies in the cat and non-human primate indicate the cerebellum is indirectly connected to this system via output pathways to the brainstem. Therefore, the cerebellum may indirectly modulate excitability of putative propriospinal neurons (PNs) in humans during upper limb coordination tasks.', 'This study aimed to test whether anodal direct current stimulation (DCS) of the cerebellum modulates PNs and upper limb coordination in healthy adults. The hypothesis was that cerebellar anodal DCS would reduce descending facilitation of PNs and improve upper limb coordination.', 'Transcranial magnetic stimulation (TMS), paired with peripheral nerve stimulation, probed activity in facilitatory and inhibitory descending projections to PNs following an established protocol. Coordination was tested using a pursuit rotor task performed by the non-dominant (ipsilateral) hand. Anodal and sham DCS were delivered over the cerebellum ipsilateral to the non-dominant hand in separate experimental sessions. Anodal DCS was applied to a control site lateral to the vertex in a third session. Twelve right-handed healthy adults participated.', 'Pairing TMS with sub-threshold peripheral nerve stimulation facilitated motor evoked potentials at intensities just above threshold in accordance with the protocol. Anodal cerebellar DCS reduced facilitation without influencing inhibition, but the reduction in facilitation was not associated with performance of the pursuit rotor task.",
            "output": [
                "Does anodal Cerebellar Direct Current Stimulation reduce Facilitation of Propriospinal Neurons in Healthy Humans?"
            ]
        },
        {
            "id": "task847-d2862f4b7a2748b3a528e232e5903865",
            "input": "The modulation of intracortical inhibition is thought to be impaired in older adults, which may contribute to their reduced fine motor control, particularly during lengthening muscle contractions.', 'To quantify the magnitude of intracortical inhibition and movement performance during postural, shortening and lengthening contractions of a hand muscle in young and old adults.', 'In 18 young (23.2 \u00b1 4.2) and 16 old (70.6 \u00b1 6.5) subjects, paired-pulse transcranial magnetic stimulation (TMS) was used to assess short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI) during a movement task involving the first dorsal interosseous muscle. The task required a constant load (50 g) to be slowly lifted and lowered using the index finger while single- or paired-pulse TMS was delivered during the shortening or lengthening contraction.', 'Relative to postural contractions, SICI during shortening contractions was reduced by 29% in young subjects (P < 0.0001) and 43% in old subjects (P < 0.0001), whereas SICI during lengthening contractions was reduced by 11% in young subjects (P = 0.0004) and 33% in old subjects (P < 0.0001). Furthermore, SICI was significantly less in older adults during lengthening contractions (P-values < 0.01). For LICI, inhibition was not influenced by contraction type in old subjects, but was increased by 11% during shortening contractions (P < 0.0001) and by 9% during lengthening contractions in young subjects (P = 0.0008). In addition, old subjects showed significantly less LICI than young subjects in each movement phase (both P-values < 0.05).",
            "output": [
                "Is intracortical Inhibition Assessed with Paired-Pulse Transcranial Magnetic Stimulation Modulated during Shortening and Lengthening Contractions in Young and Old Adults?"
            ]
        },
        {
            "id": "task847-afab98f80466470aab18fadb27f44d4a",
            "input": "The objective of this study was to estimate the time since death using pilocarpine eye drops.', 'In this study, 100 postmortem cases with known time of death were included. In each case, the left pupil was measured in millimeter units using a vernier caliper, and pilocarpine eye drops were applied. The pupil was measured again 10 min later, and statistical analysis was used to analyze the correlation between the time since death and the change in the pupil.', \"The longest duration since death that the pupils showed reaction to pilocarpine was 15 h. The correlation between the change in the pupil and the postmortem interval was found (Spearman's rho, r = -0.304, p = 0.002), and the change in the pupil may be used to predict the postmortem interval by the following regression equation: postmortem interval (PMI) = 8.310-3.702 (Diff) \u00b1 0.735 (PMI was postmortem interval in hours and Diff was the difference in the size of the pupil after administering pilocarpine in millimeter units).",
            "output": [
                "Does the use of pilocarpine eye drop for estimating the time since death?"
            ]
        },
        {
            "id": "task847-db521f2960204188ae25140d5a4d9db6",
            "input": "Studies in chronic noncancer pain settings have found that opioid use increases health care utilization. Despite the key role of analgesics, specifically opioids, in the setting of cancer pain, there is no literature to our knowledge about the relationship between adherence to prescribed around-the-clock (ATC) analgesics and acute health care utilization (hospitalization) among patients with cancer pain.', 'To identify adherence patterns over time for cancer patients taking ATC analgesics for pain, cluster these patterns into adherence types, combine the types into an adherence risk factor for hospitalization, identify other risk factors for hospitalization, and identify risk factors for inconsistent analgesic adherence.', 'Data from a 3-month prospective observational study of patients diagnosed with solid tumors or multiple myeloma, having cancer-related pain, and having at least one prescription of oral ATC analgesics were collected. Adherence data were collected electronically using the medication event-monitoring system. Analyses were conducted using adaptive modeling methods based on heuristic search through alternative models controlled by likelihood cross-validation scores.', 'Six adherence types were identified and combined into the risk factor for hospitalization of inconsistent versus consistent adherence over time. Twenty other individually significant risk factors for hospitalization were identified, but inconsistent analgesic adherence was the strongest of these predictors (ie, generating the largest likelihood cross-validation score). These risk factors were adaptively combined into a model for hospitalization based on six pairwise interaction risk factors with exceptional discrimination (ie, area under the receiver-operating-characteristic curve of 0.91). Patients had from zero to five of these risk factors, with an odds ratio of 5.44 (95% confidence interval 3.09-9.58) for hospitalization, with a unit increase in the number of such risk factors.",
            "output": [
                "Do patterns of analgesic adherence predict health care utilization among outpatients with cancer pain?"
            ]
        },
        {
            "id": "task847-2fe1697039d34e549e1398be308fd396",
            "input": "Partial DiGeorge syndrome (pDGS) is caused by deletion of the 22q11.2 region. Within this region lies CrK-like (CRKL), a gene encoding an adapter protein belonging to the Crk family that is involved in the signaling cascade of IL-2, stromal cell-derived factor 1\u03b1, and type I interferon. Although recurrent infections can be observed in patients with deletion of chromosome 22 syndrome, the immune pathogenesis of this condition is yet not fully understood.', 'We aimed to investigate the role of CRKL in T-cell functional responses in patients affected with pDGS.', 'Protein expression levels and phosphorylation of CRKL were evaluated in patients with pDGS. T-cell functional assays in\\xa0vitro and gene-silencing experiments were also performed.', 'CRKL protein expression, as well as its phosphorylation, were reduced in all patients with pDGS, especially on IL-2 stimulation. Moreover, T\\xa0cells presented impaired proliferation and reduced IL-2 production on anti-CD3/CD28 stimulation and decreased c-Fos expression. Finally, CRKL silencing in Jurkat T\\xa0cells resulted in impaired T-cell proliferation and reduced c-Fos expression.",
            "output": [
                "Is reduction of CRKL expression in patients with partial DiGeorge syndrome associated with impairment of T-cell functions?"
            ]
        },
        {
            "id": "task847-e2874305715b489c93969611c886b2a7",
            "input": "Given the modest responses to everolimus, a mTOR inhibitor, in multiple tumor types, there is a pressing need to identify predictive biomarkers for this drug. Using targeted ultra-deep sequencing, we aimed to explore genomic alterations that confer extreme sensitivity to everolimus.', 'We collected formalin-fixed paraffin-embedded tumor/normal pairs from 39 patients (22 with exceptional clinical benefit, 17 with no clinical benefit) who were treated with everolimus across various tumor types (13 gastric cancers, 15 renal cell carcinomas, 2 thyroid cancers, 2 head and neck cancer, and 7 sarcomas). Ion AmpliSeqTM Comprehensive Cancer Panel was used to identify alterations across all exons of 409 target genes. Tumors were sequenced to a median coverage of 552x. Cancer genomes are characterized by 219 somatic single-nucleotide variants (181 missense, 9 nonsense, 7 splice-site) and 22 frameshift insertions/deletions, with a median of 2.1 mutations per Mb (0 to 12.4 mutations per Mb). Overall, genomic alterations with activating effect on mTOR signaling were identified in 10 of 22 (45%) patients with clinical benefit and these include MTOR, TSC1, TSC2, NF1, PIK3CA and PIK3CG mutations. Recurrently mutated genes in chromatin remodeling genes (BAP1; n = 2, 12%) and receptor tyrosine kinase signaling (FGFR4; n = 2, 12%) were noted only in patients without clinical benefit.",
            "output": [
                "Does next-generation sequencing reveal somatic mutations that confer exceptional response to everolimus?"
            ]
        },
        {
            "id": "task847-f88bc29acde346d4ac1c6e5f122a5a8e",
            "input": "Calcipotriol ameliorates psoriasis through inducing keratinocyte apoptosis and inhibiting nuclear factor kappa B (NF-\u03baB) activation, while zinc finger protein A20 exhibits an anti-apoptotic effect on various types of cells.', 'To understand the potential role of A20 in calcipotriol function.', 'The A20 levels were evaluated in the psoriatic skins from both human patients and K14-vascular endothelial growth factor (VEGF) transgenic mice that received or did not receive topical calcipotriol treatment. The in vitro effect of calcipotriol on A20 expression and the downstream NF-\u03baB pathway was studied using a model of human foreskin keratinocytes (HFKs) that were stimulated with psoriatic cytokines [M5, a cocktail of interleukin (IL)-1a, IL-17A, IL-22, Oncostatin M and tumour necrosis factor-\u03b1, each at 10 ng mL(-1) ].', 'A20 expression was enhanced in both psoriatic tissues and keratinocytes when compared with controls, but decreased on calcipotriol treatment. The transfection of A20 small interfering RNA (siRNA) improved cell differentiation, and inhibited psoriatic inflammation in a HFK model. Moreover, the nuclear expression of NF-\u03baB p65 decreased on A20 downregulation in psoriatic tissues and keratinocytes. Interestingly, calcipotriol enhanced the binding of A20 to ring finger protein 114 (RNF114) and A20-binding inhibitor of NF-\u03baB-1 (ABIN-1) in HFKs, two negative regulators of the NF-\u03baB pathway.",
            "output": [
                "Is zinc finger protein A20 involved in the antipsoriatic effect of calcipotriol?"
            ]
        },
        {
            "id": "task847-125d1fc7a0b2471c8be43e7424e9e16c",
            "input": "Invasive species can have devastating effects on native ecosystems and therefore impose a significant threat to human welfare. The introduction rate of invasive species has accelerated dramatically in recent times due to human activity (anthropogenic effects), with a steadily growing pool of widespread tramp species. We present an in-depth analysis of four pantropical species of Xyleborus ambrosia beetles (Xyleborus volvulus, Xyleborus perforans, Xyleborus ferrugineus, and Xyleborus affinis) with similar ecology (fungus cultivation in dead wood), reproductive biology (permanent inbreeding) and genetic system (haplodiploidy). The unique combination of reproductive traits and broad host plant usage pre-adapts these beetles for colonizing of new areas.', 'We found that all four species were broadly distributed long before human-assisted dispersal became common, and that the impact of anthropogenic effects varied among the species. For X. volvulus, X. perforans, and X. affinis there was evidence of ancient establishment in numerous regions, but also of abundant recent introductions into previously colonized areas. For X. ferrugineus, we found clear biogeographical structuring of old clades, but little evidence for recent successful introductions.",
            "output": [
                "Do globally distributed Xyleborus species reveal recurrent intercontinental dispersal in a landscape of ancient worldwide distributions?"
            ]
        },
        {
            "id": "task847-270a3dfedc3340b09b52b122c575f4ac",
            "input": "The role of chitinases and chitinase-like proteins in multiple sclerosis (MS) is currently unknown; however, cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (CHI3L1) predict prognosis in early MS. Whether this applies to other chitinases and chitinase-like proteins is yet to be established. Our objective was to investigate the potential of chitinase 3-like 2 (CHI3L2) and chitotriosidase as prognostic biomarkers in optic neuritis (ON) as the first demyelinating episode and to evaluate the ability of CHI3L2 to predict long-term MS risk and disability.', 'In a prospective cohort of 73 patients with ON as a first demyelinating episode and 26 age-matched healthy controls levels of CHI3L2 and chitotriosidase in CSF were explored by enzyme-linked immunosorbent assay. Associations with magnetic resonance imaging white matter lesions, CSF oligoclonal bands, immunoglobulin G index and leukocyte count were investigated. Long-term MS risk and disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite components) were examined in a retrospective cohort of 78 patients with ON as the first demyelinating episode (mean follow-up 14 years). The predictive ability of CHI3L2 was compared with CHI3L1.', 'Cerebrospinal fluid levels of CHI3L2 and chitotriosidase were significantly elevated in patients with ON and were associated with MS risk measures. CHI3L2 levels predicted MS development after ON (hazard ratio 1.95, P = 0.00039, Cox regression) and cognitive impairment by the Paced Auditory Serial Addition Test (P = 0.0357, linear regression) at follow-up. In a multivariate analysis of MS risk, CHI3L2 performed better than CHI3L1.",
            "output": [
                "Are cerebrospinal fluid chitinase-3-like 2 and chitotriosidase potential prognostic biomarkers in early multiple sclerosis?"
            ]
        },
        {
            "id": "task847-5e41dd12a47f4bc78bad44d7d1055077",
            "input": "To evaluate the effects of artesunate on organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat.', 'HS is still a common cause of death in severely injured patients and is characterized by impairment of organ perfusion, systemic inflammatory response, and multiple organ failure. There is no specific therapy that reduces organ injury/dysfunction. Artesunate exhibits pharmacological actions beyond its antimalarial activity, such as anticancer, antiviral, and anti-inflammatory effects.', 'Rats were submitted to HS. Mean arterial pressure was reduced to 30\\u200amm Hg for 90\\u200aminutes, followed by resuscitation. Rats were randomly treated with artesunate (2.4 or 4.8\\u200amg/kg i.v.) or vehicle upon resuscitation. Four hours later, parameters of organ injury and dysfunction were assessed.', 'Artesunate attenuated the multiple organ injury and dysfunction caused by HS. Pathway analysis of RNA sequencing provided good evidence to support an effect of artesunate on the Akt-survival pathway, leading to downregulation of interleukin-1 receptor-associated kinase 1. Using Western blot analysis, we confirmed that treatment of HS rats with artesunate enhanced the phosphorylation (activation) of Protein kinase B (Akt) and endothelial nitric oxide synthase and the phosphorylation (inhibition) of glycogen synthase kinase-3\u03b2 (GSK-3\u03b2). Moreover, artesunate attenuated the HS-induced activation of nuclear factor kappa B and reduced the expression of proinflammatory proteins (inducible nitric oxide synthase, tumor necrosis factor-\u03b1, and interleukin 6).",
            "output": [
                "Does artesunate protect Against the Organ Injury and Dysfunction Induced by Severe Hemorrhage and Resuscitation?"
            ]
        },
        {
            "id": "task847-c90ab27e5bc94550a64ca8c1babf835d",
            "input": "Reduced levels of free and total insulin-like growth factor 1 (IGF-I) have been observed in type-1 diabetes (T1D) patients. The bioavailability of IGF-I from the circulation to the target cells is controlled by multifunctional IGF-binding proteins (IGFBPs). The aim of this study was to profile serum IGFBPs in T1D and its complications.', 'We measured the IGFBP levels in 3662 patient serum samples from our ongoing Phenome and Genome of Diabetes Autoimmunity (PAGODA) study. IGFBP levels of four different groups of T1D patients (with 0, 1, 2, and \u22653 complications) were compared with healthy controls.', 'Three serum IGFBPs (IGFBP-1, -2, and -6) are significantly higher in T1D patients, and these alterations are greater in the presence of diabetic complications. IGFBP-3 is lower in patients with diabetic complications. Analyses using quintiles revealed that risk of T1D complications increases with increasing concentrations of IGFBP-2 (fifth quintile ORs: 18-60, p\\u2009<\\u200910(-26)), IGFBP-1 (fifth quintile ORs: 8-20, p\\u2009<\\u200910(-15)), and IGFBP-6 (fifth quintile ORs: 3-148, p\\u2009<\\u200910(-3)). IGFBP-3 has a negative association with T1D complications (fifth quintile ORs: 0.12-0.25, p\\u2009<\\u200910(-5)).",
            "output": [
                "Do iGF-Binding Proteins in Type-1 Diabetes Are More Severely Altered in the Presence of Complications?"
            ]
        },
        {
            "id": "task847-4437e96d2858406b8f1e42e8a91ed420",
            "input": "Enhanced activation of the mineralocorticoid receptors (MRs) in cardiovascular tissues increases oxidative stress, maladaptive immune responses, and inflammation with associated functional vascular abnormalities. We previously demonstrated that consumption of a Western diet (WD) for 16 weeks results in aortic stiffening, and that these abnormalities were prevented by systemic MR blockade in female mice. However, the cell-specific role of endothelial cell MR (ECMR) in these maladaptive vascular effects has not been explored.', 'We hypothesized that specific deletion of the ECMR would prevent WD-induced increases in endothelial sodium channel activation, reductions in bioavailable nitric oxide, increased vascular remodeling, and associated increases in vascular stiffness in females.', 'Four-week-old female ECMR knockout and wild-type mice were fed either mouse chow or WD for 16 weeks. WD feeding resulted in aortic stiffness and endothelial dysfunction as determined in vivo by pulse wave velocity and ex vivo by atomic force microscopy, and wire and pressure myography. The WD-induced aortic stiffness was associated with enhanced endothelial sodium channel activation, attenuated endothelial nitric oxide synthase activation, increased oxidative stress, a proinflammatory immune response and fibrosis. Conversely, cell-specific ECMR deficiency prevented WD-induced aortic fibrosis and stiffness in conjunction with reductions in endothelial sodium channel activation, oxidative stress and macrophage proinflammatory polarization, restoration of endothelial nitric oxide synthase activation.",
            "output": [
                "Does endothelial Mineralocorticoid Receptor mediate Diet-Induced Aortic Stiffness in Females?"
            ]
        },
        {
            "id": "task847-8868ae9c52e640e2abca6508e7c89d91",
            "input": "Dexmedetomidine, a sedative agent, provides neuroprotection when administered during or before brain ischaemia. This study was designed to determine whether dexmedetomidine post-treatment induces neuroprotection against subarachnoid haemorrhage (SAH) and the mechanisms for this effect.', 'Subarachnoid haemorrhage was induced by endovascular perforation to the junction of the right middle and anterior cerebral arteries in adult rats. Dexmedetomidine was applied immediately or 2 h after onset of SAH. Neurological outcome was evaluated 2 days after SAH. Right frontal cortex area 1 was harvested 24 h after SAH for western blotting.', 'Subarachnoid haemorrhage reduced neurological scores and increased brain oedema and blood-brain barrier permeability. These effects were attenuated by dexmedetomidine post-treatment. Neuroprotection by dexmedetomidine was abolished by PD98095, an inhibitor of extracellular signal-regulated kinase (ERK) activation. Phospho-ERK, the activated form of ERK, was increased by dexmedetomidine; this activation was inhibited by PD98095.",
            "output": [
                "Does dexmedetomidine post-treatment induce neuroprotection via activation of extracellular signal-regulated kinase in rats with subarachnoid haemorrhage?"
            ]
        },
        {
            "id": "task847-3079acc9c58944db82dfa5902d6bca8e",
            "input": "The purpose of this study was to determine the prevalence of stress urinary incontinence (SUI) in recreationally active women attending gyms or exercise classes.', 'Data were collected on the frequency and severity of incontinence and the prevalence of SUI risk factors; screening for PFM dysfunction in a fitness appraisal; symptom modification strategies; knowledge of pelvic floor muscle (PFM) exercises and the Pelvic Floor First (PFF) initiative. Three hundred and sixty-one women aged 18-83 who attended exercise classes or gyms in Western Australia were surveyed.', 'Nearly half (49.3\\xa0%) of participants reported SUI, the majority of whom slight or moderate leakage. Ninety-six per cent reported at least one SUI risk factor, with the mean being 2.7 (SD\\u2009=\\u20091.4). Almost all women surveyed had heard of PFM exercises (97.2\\xa0%), but only 15.2\\xa0% of participants were screened for PFM dysfunction in a fitness appraisal. Forty-three per cent reported that a fitness instructor cued PFM activation during a workout. Less than 1 in 10 (9.7\\xa0%) of the women surveyed had heard about the PFF initiative.",
            "output": [
                "Is stress urinary incontinence highly prevalent in recreationally active women attending gyms or exercise classes?"
            ]
        },
        {
            "id": "task847-8cf857f9783a4ba395eca681b1348056",
            "input": "The adult mammalian heart has poor regenerative capacity. In contrast, the zebrafish heart retains a robust capacity for regeneration into adulthood. These distinct responses are consequences of a differential utilization of evolutionary-conserved gene regulatory networks in the damaged heart. To systematically identify miRNA-dependent networks controlling cardiac repair following injury, we performed comparative gene and miRNA profiling of the cardiac transcriptome in adult mice and zebrafish.', 'Using an integrated approach, we show that 45 miRNA-dependent networks, involved in critical biological pathways, are differentially modulated in the injured zebrafish vs. mouse hearts. We study, more particularly, the miR-26a-dependent response. Therefore, miR-26a is down-regulated in the fish heart after injury, whereas its expression remains constant in the mouse heart. Targets of miR-26a involve activators of the cell cycle and Ezh2, a component of the polycomb repressive complex 2 (PRC2). Importantly, PRC2 exerts repressive functions on negative regulators of the cell cycle. In cultured neonatal cardiomyocytes, inhibition of miR-26a stimulates, therefore, cardiomyocyte proliferation. Accordingly, miR-26a knockdown prolongs the proliferative window of cardiomyocytes in the post-natal mouse heart.",
            "output": [
                "Does comparative transcriptome profiling of the injured zebrafish and mouse hearts identify miRNA-dependent repair pathways?"
            ]
        },
        {
            "id": "task847-175efa607c9549f29f37eb886c612022",
            "input": "To examine the concentration of C-reactive protein (CRP) in relation to gestational weeks during pregnancy among Chinese women.', 'From a randomized control trial of prenatal supplementation with folic acid, iron-folic acid, and multiple micronutrients in China, we examined 834 pregnant women with CRP measured initially between 5 and 20 weeks and at follow-up between 28 and 32 weeks gestation. We calculated and plotted CRP geometric means by gestational weeks. The same analysis was repeated for women who had normal pregnancies (624 women) by excluding women with stillbirth, preterm, small for gestational age, body mass index <18.5 kg/m(2) or >30 kg/m(2) at enrollment, and hypertension or anemia during pregnancy.', 'We observed a significant positive trend between log-transformed CRP and gestational age from 5 to 20 weeks and from 28 to 32 weeks both in the full sample and in the subset of women who had normal pregnancies. CRP geometric mean was 0.81 mg/l at 5-7 weeks of gestation, 2.85 mg/l at 19-20 weeks of gestation, and 3.89 mg/l at 32 weeks of gestation. A similar increasing trend in the CRP median or percentage of elevated CRP were also observed.",
            "output": [
                "Does c-reactive protein increase with gestational age during pregnancy among Chinese women?"
            ]
        },
        {
            "id": "task847-c04c4ceb683e4a05bd788bd392854f59",
            "input": "Many fruits soften during ripening, which is important commercially and in rendering the fruit attractive to seed-dispersing animals. Cell-wall polysaccharide hydrolases may contribute to softening, but sometimes appear to be absent. An alternative hypothesis is that hydroxyl radicals ((\u2022)OH) non-enzymically cleave wall polysaccharides. We evaluated this hypothesis by using a new fluorescent labelling procedure to 'fingerprint' (\u2022)OH-attacked polysaccharides.\", 'We tagged fruit polysaccharides with 2-(isopropylamino)-acridone (pAMAC) groups to detect (a) any mid-chain glycosulose residues formed in vivo during (\u2022)OH action and (b) the conventional reducing termini. The pAMAC-labelled pectins were digested with Driselase, and the products resolved by high-voltage electrophoresis and high-pressure liquid chromatography.', 'Strawberry, pear, mango, banana, apple, avocado, Arbutus unedo, plum and nectarine pectins all yielded several pAMAC-labelled products. GalA-pAMAC (monomeric galacturonate, labelled with pAMAC at carbon-1) was produced in all species, usually increasing during fruit softening. The six true fruits also gave pAMAC\u00b7UA-GalA disaccharides (where pAMAC\u00b7UA is an unspecified uronate, labelled at a position other than carbon-1), with yields increasing during softening. Among false fruits, apple and strawberry gave little pAMAC\u00b7UA-GalA; pear produced it transiently.",
            "output": [
                "Are pectic polysaccharides attacked by hydroxyl radicals in ripening fruit : evidence from a fluorescent fingerprinting method?"
            ]
        },
        {
            "id": "task847-6055da9d8baa46afac4276eb05f19b13",
            "input": "Studies in rodents suggest that metformin treatment during pregnancy may have harmful effects on testicular development in offspring. Our aim was to determine whether metformin treatment of gestational diabetes mellitus (GDM) affects testicular size in male offspring.', 'We compared the testicular size in prepubertal boys born to mothers who participated in a randomized controlled trial (RCT) comparing metformin with insulin in the treatment of GDM. Twenty-five (42.4% of invited) and 27 (52.9% of invited) boys whose mothers had been treated with metformin or insulin, respectively, participated in the study. Testicular size was measured by a ruler, an orchidometer, and by ultrasonography at the age of 33 to 85 months.', 'The mean age of the boys was 60 months at the time of examination, and did not differ between the metformin and insulin group (p = 0.88). There was no difference in testicular size between the boys in the two groups (p always \u2265 0.40), and there were no significant differences in height, weight, BMI, BMI z-score, or waist-to-hip ratio (WHR) between the boys in the groups.",
            "output": [
                "Does metformin Treatment Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes?"
            ]
        },
        {
            "id": "task847-4323565be8fc4c1b9f9fb0478d17c23d",
            "input": "To investigate the effects of interval aerobic training combined with strength-endurance exercise (IASE) and caloric restriction (CR) on body composition, glycaemic and lipid profile and inflammatory markers.', 'Thirty-two Zucker diabetic fatty rats were randomised into 4 groups (sedentary\\xa0+\\xa0CR; sedentary\\xa0+\\xa0adlibitum; IASE\\xa0+\\xa0CR; and IASE\\xa0+\\xa0adlibitum). Training groups conducted an IASE programme in the same session, 5 days/week for 2 months. Body weight, fat and muscle mass and body water were measured using a body composition analyser. Plasma total, LDL and HDL cholesterol, phospholipids, triglycerides, insulin, adiponectin, tumour necrosis factor alpha, interleukin 1 and 10 were measured. Blood fasting and postprandial glucose were assessed. Body weight was lower in the CR compared to the adlibitum groups (p\\xa0<\\xa00.001). Fat mass was lower in the CR compared to the adlibitum (p\\xa0<\\xa00.05) and in the IASE compared to the sedentary groups (p\\xa0<\\xa00.001), but IASE increased lean mass (p\\xa0<\\xa00.001). Triglycerides were lower in the CR compared to the adlibitum groups (p\\xa0<\\xa00.001) whereas total and LDL-cholesterol and fasting glucose were reduced only in the IASE groups (all, p\\xa0<\\xa00.001). Phospholipids decreased in the CR compared to the adlibitum (p\\xa0<\\xa00.05) and the IASE compared to the sedentary groups (p\\xa0<\\xa00.001). The area under the curve after oral glucose tolerance test, insulin and homoeostatic model assessment were lower in the IASE and the CR compared to the sedentary and adlibitum groups, respectively (all, p\\xa0<\\xa00.001). Adiponectin was lower in the CR groups (p\\xa0<\\xa00.001).",
            "output": [
                "Does interval aerobic training combined with strength-endurance exercise improve metabolic markers beyond caloric restriction in Zucker rats?"
            ]
        },
        {
            "id": "task847-46834644dc5b481ca1236dcbefbfadf9",
            "input": "High dose melphalan (HDM) and autologous stem cell transplantation (ASCT) retains a central role in the treatment of myeloma. The aim of this study was to determine whether HDM exposure (area under the concentration vs. time curve, AUC), is significantly associated with transplant outcomes.', 'Melphalan concentrations were measured in six to 11 plasma samples collected after HDM (median 192\\xa0mg\\xa0m(-) (2) ) to determine melphalan AUC for a total of 114 patients. Binary logistic regression was used to assess whether melphalan AUC was associated with severe (\u2265 grade 3) oral mucositis. Multivariate Cox regression was used to assess whether melphalan AUC was significantly associated with time to progression, progression-free survival and overall survival (OS).', 'Melphalan AUC ranged from 4.9 to 24.6\\xa0mg\\xa0l(-1) \\xa0h, median 12.84\\xa0mg\\xa0l(-1) h. Melphalan AUC above the median was a risk factor for severe mucositis (HR 1.21, 95% CI 1.06, 1.38, P\\xa0=\\xa00.004) but was also associated with significantly improved overall survival (OS) (HR 0.40, 95% CI 0.20, 0.81, P\\xa0=\\xa00.001), with an estimated median survival of 8.50\\xa0years vs. 5.38\\xa0years for high vs. low AUC groups. Multivariate analysis did not identify melphalan AUC as being significantly associated with time to progression or progression-free survival.",
            "output": [
                "Is high melphalan exposure associated with improved overall survival in myeloma patients receiving high dose melphalan and autologous transplantation?"
            ]
        },
        {
            "id": "task847-fd746f2a671a417281d86830aa186e3e",
            "input": "The contribution of genetic variability to clinical heterogeneity in Parkinson's disease is insufficiently understood. We aimed to investigate the effect of cumulative genetic risk on clinical outcomes.\", \"In a single-center study of 336 patients we genotyped 19 independent susceptibility variants identified in genome-wide association studies of Parkinson's disease. We tested for association between a cumulative genetic risk score and 3 outcome measures: survival, time until progression to Hoehn and Yahr stage 3, and Unified Parkinson's Disease Rating Scale motor score severity.\", 'Genetic risk score was significantly associated with time from diagnosis to Hoehn and Yahr stage 3 in a Cox regression model (P = 0.010). We observed no clear association for the other outcomes.",
            "output": [
                "Does a cumulative genetic risk score predict progression in Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-412c9e46cfa24bc2ae3cb42ccf09c2b3",
            "input": "The geriatric population is rapidly increasing in number with increased demand on health care resources including those spent on the treatment of maxillofacial trauma. The purpose of this analysis was to investigate the independent and cumulative associations between potential risk factors (age, gender, mechanism of injury, drug use, and alcohol use) for and the severity of geriatric facial trauma.', 'This was a cross-sectional analysis of secondary data of geriatric (individuals aged \u226565\\xa0years) facial trauma using the Allegheny General Hospital Trauma Registry database. Data were collected for diagnosis codes that reflected facial trauma (International Classification of Diseases, Ninth Revision codes 802.0 to 802.9, 800.1 to 801.9, and 803.0 to 804.9) and specific mechanisms of injury (E810 to E819, motor vehicle traffic accidents; E880 to E888, accidental falls; and E960 to E969, injury purposely inflicted by other persons). The Facial Injury Severity Scale (FISS) is a validated measurement that was used to determine the severity of the facial trauma and calculated through analysis of the abstracted data obtained from the trauma registry and patient records. Pearson correlations, 2-way independent t test, 1-way analysis of variance, and multiple linear regression were used to test hypotheses for independent and cumulative associations between the risk factors for and the severity of geriatric facial trauma. Statistical significance was set at the P < .05 level.', 'The sample was composed of 229 patients with a mean age of 72.3 \u00b1 4.5\\xa0years. A statistically significant association between mechanism of injury and the severity of geriatric facial trauma (P\\xa0= .019) was found. Specifically, interpersonal violence (assault) was associated with the greatest facial trauma severity (FISS score, 4.2) when compared with motor vehicle collisions (FISS score, 2.2; P\\xa0= .011) and falls (FISS score, 2.4; P\\xa0= .016).",
            "output": [
                "Does interpersonal Violence be Associated With Increased Severity of Geriatric Facial Trauma?"
            ]
        },
        {
            "id": "task847-7d58c64877974c6b88a24dcb6b2db3a9",
            "input": "Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is caused by Lynch syndrome (LS) in 3% and sporadic inactivation of MLH1 by hypermethylation (MLH1-hm) in 12% of cases. It is not clear whether outcomes between LS-associated and MLH1-hm CRC differ. The objective of this study was to explore differences in clinical factors and outcomes in these two groups.', \"Patients with dMMR CRC identified by immunohistochemistry staining and treated at a single institution from 1998 to 2012 were included. MLH1-hm was established with BRAF mutational analysis or hypermethylation testing. Patients' charts were accessed for information on pathology, germ-line MMR mutation testing, and clinical course.\", 'A total of 143 patients had CRC associated with LS (37 patients, 26%) or MLH1-hm (106 patients, 74%). Patients with LS were younger, more often male, presented more often with stage III disease, and had more metachronous disease than patients with MLH1-hm tumors. There was no difference in cancer-specific survival (CSS) between the groups; overall survival was longer in patients with LS, but this difference was minimal after adjusting for age and stage at diagnosis.",
            "output": [
                "Do patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses?"
            ]
        },
        {
            "id": "task847-ec61afbe0c784a7484549ecea78a413e",
            "input": "Although elevated serum IgE levels have been reported in psoriasis, the role of IgE in psoriasis still needs to be clarified.', 'To analyse serum total IgE levels in addition to the presence and distribution of IgE and Fc\u03b5RI in psoriatic lesions, and to investigate alteration of IgE and Fc\u03b5RI after successful systemic treatment.', 'Total serum IgE levels were determined using enzyme-linked immunosorbent assay. The expression and localization of IgE and Fc\u03b5RI was investigated using immunohistochemistry and double immunofluorescence.', 'Elevated total serum IgE levels were found in 39% of patients with psoriasis. The levels of total serum IgE were significantly higher in male patients compared with female patients. Furthermore, total serum IgE levels decreased after successful systemic treatment. A positive correlation between IgE+ and Fc\u03b5RI+ cells and a significant increase of these cells was found in psoriatic lesions when compared with normal skin. Interestingly, IgE+ and Fc\u03b5RI+ cells decreased significantly after successful therapy with ustekinumab. IgE and Fc\u03b5RI were coexpressed on mast cells, epidermal Langerhans cells, dermal dendritic cells, macrophages and a small number of neutrophils.",
            "output": [
                "Are igE and Fc\u03b5RI highly expressed on innate cells in psoriasis?"
            ]
        },
        {
            "id": "task847-79132b99c28a4319bfdd58317d5ff45d",
            "input": "Thromboxane A2 (TXA2) receptors (TP) interact with the ligand TXA2 to induce platelet aggregation and regulate hemostasis. Recently TP-mediated signaling has been suggested to function in multiple cell types in the brain. In this report, we aim to study the expression and physiological role of TP in microglia, in particular after brain ischemia.', 'Ischemic brain sections were analyzed for TP expression. Microglial cell line and primary microglia were cultured, or neuronal cell line co-culture system was used to determine the TP mediated signaling in inflammation and microglia activation.', 'We found that the TP level was significantly increased in ipsilateral mouse brain tissue at 24 h after ischemia-reperfusion, which was also found to partly co-localize with CD11b, a marker for microglial and infiltrated monocyte/macrophage, in peri-infarct area. Immunofluorescence staining of primary microglia and microglial cell line BV2 revealed the predominant membrane distribution of TP. Conditioned culture media from TP agonist U46619-treated BV2 cells decreased neuronal SH-SY5Y cell viability and induced apoptotic morphological changes. Furthermore, U46619 enhanced IL-1\u03b2, IL-6, and iNOS mRNA expression as well as IL-1\u03b2 and NO releases in BV2 cells or primary microglia. Such stimulation could be attenuated by TP antagonist SQ29548 or MEK inhibitor U0126. The dose- and time-dependent extracellular-signal-regulated kinase (ERK) phosphorylation induced by U46619 further demonstrated ERK signaling-mediated microglia activation by TP agonist.",
            "output": [
                "Does thromboxane A2 Receptor Stimulation enhance Microglial Interleukin-1\u03b2 and NO Biosynthesis Mediated by the Activation of ERK Pathway?"
            ]
        },
        {
            "id": "task847-ee17a88c0c5e49068b5dafad67e6ba06",
            "input": "Human mesenchymal stromal cells (MSCs) can be isolated from different sources including bone marrow and term placenta. These two populations display distinct patterns of proliferation and differentiation in vitro. Since proliferation and differentiation of cells are modulated by cell-matrix interactions, we investigated the attachment of MSCs to a set of peptide-coated surfaces and explored their interactions with peptides in suspension.', 'Human MSCs were isolated from bone marrow and term placenta and expanded. Binding of MSCs to peptides was investigated by a cell-attachment spot assay, by blocking experiments and flow cytometry. The integrin expression pattern was explored by a transcript array and corroborated by quantitative reverse transcription polymerase chain reaction and flow cytometry.', 'Expanded placenta-derived MSCs (pMSCs) attached well to surfaces coated with fibronectin-derived peptides P7, P15, and P17, whereas bone marrow-derived MSCs (bmMSCs) attached to P7, but barely to P15 and P17. The binding of bmMSCs and pMSCs to the peptides was mediated by \u03b21 integrins. In suspension, expanded bmMSCs barely bind to P7, P13, P15, and less to P14 and P17. Ex vivo, bmMSCs failed to bind P7, but displayed a weak interaction with P13, P14, and P15. In suspension, expanded pMSCs displayed binding to many peptides, including P4, P7, P13, P14, P15, and P17. The differences observed in binding of bmMSCs and pMSCs to the peptides were associated with significant differences in expression of integrin \u03b12-, \u03b14-, and \u03b16-chains.",
            "output": [
                "Do bone marrow-derived mesenchymal stromal cells differ in their attachment to fibronectin-derived peptides from term placenta-derived mesenchymal stromal cells?"
            ]
        },
        {
            "id": "task847-c8701e13eb4e44d4bce7baeb0c53d295",
            "input": "Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy.', 'Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC-IC) assay and colony-forming cell (CFC) assay.', 'MYXV initiated infection in up to 45% of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95% of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10% of CD34(+) cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation.",
            "output": [
                "Does ex vivo virotherapy with myxoma virus impair hematopoietic stem and progenitor cells?"
            ]
        },
        {
            "id": "task847-c19c1d1c570c4206a5d8c416dab1ce50",
            "input": "Cord blood (CB) hematopoietic stem cell transplantation has often been limited by the scarcity of stem cells. Therefore, the number of CB hematopoietic stem/progenitor cells (HSPCs) should be increased while maintaining the stem cell characteristics.', 'We designed an ex vivo culture system using endothelial progenitor cells (EPCs) as stroma to determine the capacity of expanding CB-HSPCs in a defined medium, the effect on engraftment of the expanded cells in a mouse model and the underlying mechanism.', \"After 7 days of culture, compared with those cultured with cytokines alone (3.25 \u00b1 0.59), CD34+ cells under contact and non-contact co-culture with EPCs were expanded by 5.38 \u00b1 0.61 (P = 0.003) and 4.06 \u00b1 0.43 (P = 0.025)-fold, respectively. Direct cell-to-cell contact co-culture with EPCs resulted in more primitive CD34+ CD38- cells than stroma-free culture (156.17 \u00b1 21.32 versus 79.12 \u00b1 19.77-fold; P = 0.010). Comparable engraftment of day 7 co-cultured HSPCs with respect to HSPCs at day 0 in nonobese diabetic-severe combined immunodeficiency disease (NOD/SCID) mice was measured as a percentage of chimerism (13.3% \u00b1 11.0% versus 16.0% \u00b1 14.3%; P = 0.750). EPCs highly expressed interleukin 6 (IL6) and angiopoietin 1 (ANGPT1), the hematopoietic- related cytokines. A higher transcriptional level of WNT5A genes in EPCs and co-cultured HSPCs suggests that the activation of Wnt signaling pathway may play a role in HSPCs' expansion ex vivo.",
            "output": [
                "Do endothelial progenitor cells promote efficient ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells?"
            ]
        },
        {
            "id": "task847-0078428b59b541719b2ae1d9feb63236",
            "input": "Specific and effective therapy for prevention or reversal of bronchiolitis obliterans (BO) is lacking. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF) gene modified mesenchymal stromal cells (MSCs) on BO.', 'A mouse model of experimental BO was established by subcutaneously transplanting the tracheas from C57BL/6 mice into Balb/C recipients, which were then administered saline, Ad-HGF-modified human umbilical cord-MSCs (MSCs-HGF) or Ad-Null-modified MSCs (MSCs-Null). The therapeutic effects of MSCs-Null and MSCs-HGF were evaluated by using fluorescence-activated cell sorting (FACS) for lymphocyte immunophenotype of spleen, enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (rt-PCR) for cytokine expression, and histopathological analysis for the transplanted trachea.', 'The histopathologic recovery of allograft tracheas was improved significantly after MSCs-Null and MSCs-HGF treatment and the beneficial effects were particularly observed in MSCs-HGF-treated mice. Furthermore, the allo-transplantation-induced immunophenotype disorders of the spleen, including regulatory T (Treg), T helper (Th)1, Th2 and Th17, were attenuated in both cell-treated groups. MSCs-HGF treatment reduced expression and secretion of inflammation cytokines interferon-gamma (IFN-\u03b3), and increased expression of anti-inflammatory cytokine interleukin (IL)-4 and IL-10. It also decreased the expression level of the profibrosis factor transforming growth factor (TGF)-\u03b2.",
            "output": [
                "Does hepatocyte growth factor enhance the inflammation-alleviating effect of umbilical cord-derived mesenchymal stromal cells in a bronchiolitis obliterans model?"
            ]
        },
        {
            "id": "task847-dadcb344aaaa46098aa9a699e04936c8",
            "input": "Gastric cancer (GC) is the third most common cancer in India and is mediated by multiple genetic, epigenetic and environmental risk factors. A single nucleotide polymorphism rs3025058 at -1171 of the stromelysin-1 (matrix metalloproteinase [MMP]-3) promoter is resulting due to insertion/deletion of adenine thought to have an impact on increasing the risk for tumor formation.', 'This study is aimed to understand the role of stromelysin-1 rs3025058 (-1171, 5A/6A) promoter polymorphism in the etiology of GC in Indian population.', 'Genomic DNA was isolated from blood samples of the GC patients and controls. The genotyping of stromelysin-1 rs3025058 (-1171, 5A/6A) promoter polymorphism was carried out by amplification refractory mutation system-polymerase chain reaction method followed by agarose gel electrophoresis.', 'The frequency of 5A/5A, 5A/6A, and 6A/6A genotypes in GC patients were 7.69%, 76.92%, and 15.38%, while in controls were 5.31%, 86.73%, and 7.96%, respectively. There was a significant difference in the distribution of 5A/6A genotype in patients compared to the controls (P < 0.05).",
            "output": [
                "Is heterozygosity of stromelysin-1 ( rs3025058 ) promoter polymorphism associated with gastric cancer?"
            ]
        },
        {
            "id": "task847-7033f859cc154e35bbf2513d113dcdad",
            "input": "Systemic mastocytosis is a clonal myeloproliferative neoplasm associated with constitutional symptoms from mast cell mediated chemical and cytokine release. According to the literature, Ruxolitinib, a JAK1/JAK2 inhibitor, has been shown to reduce symptoms related to proinflammatory cytokine release in other myeloproliferative neoplasms.', 'Here we present a case using Ruxolitinib for disabling constitutional symptoms despite complete bone marrow response in a patient with aggressive systemic mastocytosis. Assessment tools used to monitor symptoms in previously published Ruxolitinib trials were adopted to track symptom improvement and quality of life.",
            "output": [
                "Does ruxolitinib improve symptoms and quality of life in a patient with systemic mastocytosis?"
            ]
        },
        {
            "id": "task847-42cb6a71fef84b98b22b398d558e38f1",
            "input": "Recently, it has been shown that exposure to welding fumes containing both zinc and copper leads to asymptomatic systemic inflammation in humans as shown by an increase of blood C-reactive protein. In the present study, it was investigated which metal is responsible for this effect.', 'Fifteen healthy male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc.', 'For each exposure blood C-reactive protein increased.",
            "output": [
                "Does single and Combined Exposure to Zinc- and Copper-Containing Welding Fumes lead to Asymptomatic Systemic Inflammation?"
            ]
        },
        {
            "id": "task847-0fe3f83cd8784658880adc76fccba71d",
            "input": "Low rates of compliance with quality measures for inflammatory bowel disease (IBD) have been reported for US gastroenterologists.', 'We assessed the influence of quality improvement (QI) education on compliance with physician quality reporting system (PQRS) measures for IBD and measures related to National Quality Strategy (NQS) priorities.', \"Forty community-based gastroenterologists participated in the QI study; 20 were assigned to educational intervention and control groups, respectively. At baseline, randomly selected charts of patients with moderate-to-severe ulcerative colitis were retrospectively reviewed for the gastroenterologists' performance of 8 PQRS IBD measures and 4 NQS-related measures. The intervention group participated in a series of accredited continuing medical education (CME) activities focusing on QI. Follow-up chart reviews were conducted 6\\xa0months after the CME activities. Independent t tests were conducted to compare between-group differences in baseline-to-follow-up rates of documented compliance with each measure.\", 'The analysis included 299 baseline charts and 300 follow-up charts. The intervention group had significantly greater magnitudes of improvement than the control group for the following measures: assessment of IBD type, location, and activity (+14\\xa0%, p\\xa0=\\xa00.009); influenza vaccination (+13\\xa0%, p\\xa0=\\xa00.025); pneumococcal vaccination (+20\\xa0%, p\\xa0=\\xa00.003); testing for latent tuberculosis before anti-TNF-\u03b1 therapy (+10\\xa0%, p\\xa0=\\xa00.028); assessment of hepatitis B virus status before anti-TNF-\u03b1 therapy (+9\\xa0%, p\\xa0=\\xa00.010); assessment of side effects (+17\\xa0%, p\\xa0=\\xa00.048), and counseling patients about cancer risks (+13\\xa0%, p\\xa0=\\xa00.013).",
            "output": [
                "Does continuing Medical Education improve Gastroenterologists ' Compliance with Inflammatory Bowel Disease Quality Measures?"
            ]
        },
        {
            "id": "task847-280c10ee31f74715acb4f73cf456190d",
            "input": "Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia.', 'We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist.', 'In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels.",
            "output": [
                "Does circulating Hepcidin-25 be Reduced by Endogenous Estrogen in Humans?"
            ]
        },
        {
            "id": "task847-cb5c36bbf51e405287eece2f0ec14050",
            "input": "Lung cancer is the most common cause of cancer deaths in the United States. Overall survival is less than 20%, with the majority of patients presenting with advanced disease. The National Lung Screening Trial, performed mainly in academic medical centers, showed that cancer mortality can be reduced with computed tomography (CT) screening compared with chest radiography in high-risk patients. To determine whether this survival advantage can be duplicated in a community-based multidisciplinary thoracic oncology program, we initiated a CT scan screening program for lung cancer within an established health care system.', 'In 2008, we launched a lung cancer CT screening program within the WellStar Health System (WHS) consisting of five hospitals, three health parks, 140 outpatient medical offices, and 12 imaging centers that provide care in a five-county area of approximately 1.4 million people in Metro-Atlanta. Screening criteria incorporated were the International Early Lung Cancer Action Program (2008 to 2010) and National Comprehensive Cancer Network guidelines (2011 to 2013) for moderate- and high-risk patients.', 'A total of 1,267 persons underwent CT lung cancer screening in WHS from 2008 through 2013; 53% were men, 87% were 50 years of age or older, and 83% were current or former smokers. Noncalcified indeterminate pulmonary nodules were found in 518 patients (41%). Thirty-six patients (2.8%) underwent a diagnostic procedure for positive findings on their CT scan; 30 proved to have cancer, 28 (2.2%) primary lung cancer and 2 metastatic cancer, and 6 had benign disease. Fourteen patients (50%) had their lung cancer discovered on their initial CT scan, 11 on subsequent scans associated with indeterminate pulmonary nodules growth and 3 patients who had a new indeterminate pulmonary nodules. Only 15 (54%) of these 28 patients would have qualified as a National Lung Screening Trial high-risk patient; 75% had stage I or II disease. Overall 5-year survival was 64% and 5-year cancer specific survival was 71% in the screened patients, whereas nonscreened lung cancer patients during that time in WHS had an overall survival of only 19% (p < 0.001).",
            "output": [
                "Does community-Based Multidisciplinary Computed Tomography Screening Program improve Lung Cancer Survival?"
            ]
        },
        {
            "id": "task847-abc2a7113a9e472ba4569eef16fabb74",
            "input": "Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.', 'We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p\\u2009<\\u20090.05 and FC\\u2009\u2265\\u20091.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results.', 'Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p\\u2009=\\u20094.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways.",
            "output": [
                "Are mitochondrial and oxidative stress genes differentially expressed in neutrophils of sJIA patients treated with tocilizumab : a pilot microarray study?"
            ]
        },
        {
            "id": "task847-9d7babf3fd3844f38c1b8b27fde1fd01",
            "input": "Transcatheter arterial chemoembolization is currently the standard treatment in hepatocellular carcinoma patients with Barcelona Clinic Liver Cancer stage B. Genomic variants of GALNT14 were recently identified as effective predictors for chemotherapy responses in Barcelona Clinic Liver Cancer stage C patients.', 'We investigated the prognosis predictive value of GALNT14 genotypes in 327 hepatocelluar carcinoma patients treated by transcatheter arterial chemoembolization.', \"Cox proportional hazards model analysis showed that the genotype 'TT' was associated with shorter time-to-response (multivariate p < 0.001), time-to-complete-response (p = 0.004) and longer time-to-tumor progression (p < 0.001), compared with the genotype 'non-TT'. In patients with albumin <3.5 g/dl, genotype 'TT' was associated with longer overall survival (p = 0.027). Finally, genotype 'TT' correlated with higher cancer-to-noncancer ratios of GALNT14 protein levels, lower cancer-to-noncancer ratios of antiapoptotic cFLIP-S, and a clustered glycosylation pattern in the extracellular domain of death receptor 5.",
            "output": [
                "Does gALNT14 genotype effectively predict the therapeutic response in unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization?"
            ]
        },
        {
            "id": "task847-9aa14a50b7584d2886f9d11899ab9a0d",
            "input": "Child undernutrition and flooding are highly prevalent public health issues in Asia, yet epidemiological studies investigating this association are lacking.', 'To investigate to what extent floods exacerbate poor nutritional status in children and identify most vulnerable groups, we conducted a population-based survey of children aged 6-59 months inhabiting flooded and non-flooded communities of the Jagatsinghpur district, Odisha (India), one year after large floods in 2008. Anthropometric measurements on 879 children and child, parental and household level variables were collected through face-to-face interviews in September 2009. The association between flooding and the prevalence of wasting, stunting and underweight was examined using weighted multivariate logistic regression for children inhabiting communities exposed solely to floods in 2008 and those communities repeatedly flooded (2006 and 2008) controlling for parental education and other relevant variables. We examined the influence of age on this association. Propensity score matching was conducted to test the robustness of our findings.', 'The prevalence of wasting among children flooded in 2006 and 2008 was 51.6%, 41.4% in those flooded only in 2008, and 21.2% in children inhabiting non-flooded communities. Adjusting by confounders, the increased prevalence relative to non-flooded children in the exposed groups were 2.30 (adjusted prevalence ratio (aPR); 95% CI: 1.86, 2.85) and 1.94 (95% CI: 1.43, 2.63), respectively. Among repeatedly flooded communities, cases of severe wasting in children were 3.37 times more prevalent than for children inhabiting in those non-flooded (95% CI: 2.34, 4.86) and nearly twice more prevalent relative to those flooded only once. Those children younger than one year during previous floods in 2006 showed the largest difference in prevalence of wasting compared to their non-flooded counterparts (aPR: 4.01; 95% CI: 1.51, 10.63). RESULTS were robust to alternative adjusted models and in propensity score matching analyses. For similar analyses, no significant associations were found for child stunting, and more moderate effects were observed in the case of child underweight.",
            "output": [
                "Is flood-Exposure Associated with Higher Prevalence of Child Undernutrition in Rural Eastern India?"
            ]
        },
        {
            "id": "task847-3535224c73e74c6aac1c2f0ca3f0076a",
            "input": "Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy) is induced, these cells are chemosensitive and will not recover following chemotherapy treatment. In contrast, when cancer cells exhibit only autophagy and limited Type II cell death, they are chemoresistant and recover following drug withdrawal.', 'MicroRNA (miRNA) expression profiling of an oesophageal cancer cell line panel was used to identify miRNAs that were important in the regulation of apoptosis and autophagy. The effects of miRNA overexpression on cell death mechanisms and recovery were assessed in the chemoresistant (autophagy inducing) KYSE450 oesophageal cancer cells.', 'MiR-193b was the most differentially expressed miRNA between the chemosensitive and chemoresistant cell lines with higher expression in chemosensitive apoptosis inducing cell lines. Colony formation assays showed that overexpression of miR-193b significantly impedes the ability of KYSE450 cells to recover following 5-fluorouracil (5-FU) treatment. The critical mRNA targets of miR-193b are unknown but target prediction and siRNA data analysis suggest that it may mediate some of its effects through stathmin 1 regulation. Apoptosis was not involved in the enhanced cytotoxicity. Overexpression of miR-193b in these cells induced autophagic flux and non-apoptotic cell death.",
            "output": [
                "Does miR-193b promote autophagy and non-apoptotic cell death in oesophageal cancer cells?"
            ]
        },
        {
            "id": "task847-8159ef0c74f649428458162e78eae552",
            "input": "More than 90% of anal condyloma is attributed to nonhigh risk strains of human papillomavirus (HPV), thus patients with anal condyloma do not necessarily undergo HPV serotyping unless they are immunocompromised (IC). We hypothesized that IC patients with anal condyloma have a higher risk of high-risk HPV and dysplasia than nonimmunocompromised (NIC) patients.', 'We performed a retrospective chart review of patients who underwent surgical treatment by a single surgeon for anal condyloma from 1/2000 to 1/2012. HPV serotyping was performed on all patient samples. We compared incidence of high-risk HPV and dysplasia in condyloma specimens from IC and NIC patients.', 'High-risk HPV was identified in 14 specimens with serotypes 16, 18, 31, 33, 51, 52, and 67. Twenty-two cases (18.3%) had dysplasia. Invasive carcinoma was identified in one IC patient. The prevalence of dysplasia or high-risk HPV was not significantly different between IC and NIC groups. High-risk HPV was a significant independent predictor of dysplasia (odds ratio [OR] = 5.2; 95% CI = 1.24-21.62). Immune status, however, was not a significant predictor of high-risk HPV (OR = 1.11; 95% CI = 0.16-5.12) nor dysplasia (OR = 0.27; 95% CI = 0.037-1.17).",
            "output": [
                "Does immune status predict high-risk HPV in anal condyloma?"
            ]
        },
        {
            "id": "task847-c415139ff0c741c68e8a8e9e83931275",
            "input": "Oral mucositis (OM) is a relevant adverse effect of anticancer therapy involving ionizing radiation (IR) and doxorubicin (Doxo). Because DNA damage of keratinocytes is causative for the pathogenesis of OM, we aim to identify pharmacological measures for geno- and cytoprotection of keratinocytes.', 'We investigated the influence of the lipid-lowering drug lovastatin on cell death, proliferation and DNA damage response (DDR) mechanisms of human keratinocytes following treatment with IR and Doxo.', 'Lovastatin protected keratinocytes from the cytotoxic and genotoxic effects of IR and Doxo as shown by a diminished induction of apoptosis as well as a reduced formation and slightly improved repair of DNA damage following Doxo and IR treatment, respectively. Lovastatin selectively blocked the activation of Chk1 and ATR kinases following treatment with IR, Doxo and the ribonucleotide reductase inhibitor hydroxyurea, indicating that the statin antagonizes ATR/Chk1-regulated replicative stress responses. Part of the cytoprotective activity of lovastatin seems to rest on a delayed entry of lovastatin treated cells into S-phase. Yet, because the statin also protected non-proliferating keratinocytes from IR- and Doxo-induced cytotoxicity, cell cycle independent protective mechanisms are involved, too.",
            "output": [
                "Does lovastatin protect keratinocytes from DNA damage-related pro-apoptotic stress responses stimulated by anticancer therapeutics?"
            ]
        },
        {
            "id": "task847-6b8a4321f1384b8bb4f4907441188e52",
            "input": "The counterbalance of macrophage migration inhibitory factor (MIF) and Gremlin-1 is a useful tool to predict the acuity of coronary artery disease (CAD) and plaque stability. Gremlin1 is an endogenous antagonist of MIF and therefore influences plaque vulnerability. This study was designed to elucidate the mechanistic basis determining the biophysical binding of Gremlin-1 to MIF.', 'An in silico model suggested that several charged C-terminal amino acids are crucial in mediating Gremlin-1/MIF-binding. We produced several single amino acid exchange mutants of Gremlin-1 by site-directed mutagenesis. These Gremlin-1 mutants were tested for their ability to reduce MIF effects on monocytes.', 'We observed that the critical element of the Gremlin-1 molecule for regulating MIF-induced chemotactic activity lies at the C-terminal region. A single amino acid exchange of an arginine to an alanine residue is sufficient to abolish the antagonistic effect of Gremlin-1 on MIF. Therefore, the Gremlin-1 mutant R172A failed to reduce MIF-induced monocyte differentiation into macrophages.",
            "output": [
                "Does gremlin-1 C-Terminus regulate Function of Macrophage Migration Inhibitory Factor ( MIF )?"
            ]
        },
        {
            "id": "task847-57d3eb22a1aa4462ae8ae4938d3a6f1a",
            "input": "Endothelial progenitor cells (EPCs) are key elements in vascular homeostasis. Their function is regulated by estrogens and estrogen receptors (ERs), but the effect of estrogenic compounds such as bisphenol A (BPA; an agonist of ER-\u03b2 and agonist and antagonist of ER-\u03b1) and (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol (THC; an agonist of ER-\u03b1 and antagonist of ER-\u03b2) on human EPCs is unknown. We analyzed whether BPA and THC influence the migration of human EPCs, an essential process in endothelial regeneration, in both male and female EPCs.', 'EPCs isolated from healthy adult men and women were assayed for ER expression by Western blotting and chemotaxis assay.', 'Male and female EPCs similarly expressed ERs and did not differ in basal migration. Interestingly, 17-\u03b2-estradiol (10(-9) and 10(-10) M) significantly inhibited migration in female EPCs but not in males. Moreover, both 10(-5) M THC and 10(-8) M BPA blocked migration in female EPCs, allowing us to hypothesize that the effect is mediated by ER-\u03b1.",
            "output": [
                "Do estrogenic Compounds Have Divergent Effects on Human Endothelial Progenitor Cell Migration according to Sex of the Donor?"
            ]
        },
        {
            "id": "task847-626bb291205540f5b181928dcca13c81",
            "input": "Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2.', 'Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages.",
            "output": [
                "Does lipoicmethylenedioxyphenol reduce Experimental Atherosclerosis through Activation of Nrf2 Signaling?"
            ]
        },
        {
            "id": "task847-173ee47899394e44beab2f66482584ec",
            "input": "Intellectual disability (ID) features in numerous heritable medical conditions that result from ATRX mutations. Alpha-thalassemia mental retardation syndrome (ATR-X syndrome) is the most notable manifestation of ATRX dysfunction. In addition to ID, genitourinary and craniofacial abnormalities are regularly observed with or without alpha-thalassemia.', 'The study sought to characterize two cases of ATR-X in a Yemeni family clinically and molecularly.', 'PCR amplification and Sanger sequencing were used to study the ATRX gene in a Yemeni family. Also, methylation-sensitive PCR was used to perform X-inactivation studies. CADD, SNAP2 and PolyPhen-2 helped to predict the functional consequences of the variant.', 'Molecular testing revealed a novel hemizygous missense mutation (c.5666T>G) in the ATRX gene in the two Yemeni brothers. This mutation was found in a heterozygous state in the mother, with the chromosome harboring the mutated allele being under strongly skewed X-inactivation.",
            "output": [
                "Does a novel missense mutation in ATRX uncovered in a Yemeni family lead to alpha-thalassemia/mental retardation syndrome without alpha-thalassemia?"
            ]
        },
        {
            "id": "task847-b9607d30091848179bb4ceb4ce996549",
            "input": "Replacing live-attenuated oral poliovirus vaccines (OPV) with inactivated poliovirus vaccines (IPV) is part of the global strategy to eradicate poliomyelitis. China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks. Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV (Poliorix\u2122, GSK Vaccines, Belgium) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China.', 'In pilot safety studies, 25 infants received 3-dose IPV primary vaccination (Study A, www.clinicaltrial.gov NCT00937404) and 25 received an IPV booster after priming with three OPV doses (Study B, NCT01021293). In the randomised, controlled immunogenicity and safety trial (Study C, NCT00920439), infants received 3-dose primary vaccination with IPV (N=541) or OPV (N=535) at 2,3,4 months of age, and a booster IPV dose at 18-24 months (N=470, Study D, NCT01323647: extension of study C). Blood samples were collected before and one month post-dose-3 and booster. Reactogenicity was assessed using diary cards. Serious adverse events (SAEs) were captured throughout each study.', 'Study A and B showed that IPV priming and IPV boosting (after OPV) was safe. Study C: One month post-dose-3, all IPV and \u2265 98.3% OPV recipients had seroprotective antibody titres towards each poliovirus type. The immune response elicited by IPV was non-inferior to Chinese OPV. Seroprotective antibody titres persisted in \u2265 94.7% IPV and \u2265 96.1% OPV recipients at 18-24 months (Study D). IPV had a clinically acceptable safety profile in all studies. Grade 3 local and systemic reactions were uncommon. No SAEs were related to IPV administration.",
            "output": [
                "Is primary and booster vaccination with an inactivated poliovirus vaccine ( IPV ) immunogenic and well-tolerated in infants and toddlers in China?"
            ]
        },
        {
            "id": "task847-c750aeb164794871a2e2740359344f07",
            "input": "Chronic rhinosinusitis (CRS) is a common inflammatory disease of the upper airways that is often categorized into subtypes including \"with\" and \"without\" nasal polyps. However, the influence of multiple important epidemiologic factors, including race, on CRS has not been investigated.', 'The present study assessed various phenotypic characteristics of CRS in patients, living in the United States, with different racial backgrounds.', 'We performed a large retrospective cohort study of patients with CRS treated at a large urban tertiary care referral center in Chicago.', 'African American (AA) patients with CRS living in Chicago were more likely to report hyposmia as a symptom of CRS. Furthermore, AA patients with CRS who failed medical therapy and required surgical intervention had a significantly higher frequency of nasal polyposis and aspirin-exacerbated respiratory disease, and a higher disease severity index on computed tomography imaging than did white patients with CRS. The increased polyposis in AAs was associated with increased hospitalization for asthma. There were no differences in the prevalence of atopy, asthma, atopic dermatitis, food allergy, duration of disease, or number of surgeries between different races.",
            "output": [
                "Do african American Patients with Chronic Rhinosinusitis Have a Distinct Phenotype of Polyposis Associated with Increased Asthma Hospitalization?"
            ]
        },
        {
            "id": "task847-0de6ce484b924094af668ef264e14726",
            "input": "Our previous studies (Int J Nanomed 10:22, 2015) have indicated that a single large dose of mesoporous silica nanoparticles (MSNs) can induce severe and selective nephrotoxicity, which is closely related to inflammation mediated by the NF-\u03baB pathway. However, the effect of MSNs on other organs and the interactions of nanomaterials with biological systems remain rudimentary.', 'This study aimed to clarify the biological behaviour and influence of MSNs on macrophages.', 'The mice received a single intraperitoneal injection of a suspension of 150, 300 of 600 mg/kg MSNs, and RAW 264.7 cells were treated with MSNs at various concentrations and times. Cell viability was determined by MTT assay and LDH release assay. The NF-\u03baB pathway and the target proinflammatory cytokines IL-1\u03b2 and TNF-\u03b1 were determined by western blotting or ELISA. Autophagy is considered as an emerging mechanism of nanomaterials. So the autophagic ultrastructural analysis, the determination of Beclin-1 and LC3 expression, and the calculation of LC3II dots were employed to verify autophagy activation. In addition, RNA interference, autophagy agonist and inhibitor were used to explore the role of autophagy in inflammation.', 'The results indicated that MSNs are internalized into macrophages and induce cytotoxicity in a dose- and time-dependent manner. The NF-\u03baB pathway, IL-1\u03b2 and TNF-\u03b1 were induced and released by MSNs. The levels of Beclin-1 and LC3II dots were obviously up-regulated by MSNs, which indicated that autophagy was induced in the MSN-treated cells. Moreover, the enhanced autophagy can attenuate the inflammation mediated by the NF-\u03baB pathway, whereas the inhibition of autophagy can contribute to inflammation.",
            "output": [
                "Does autophagy upregulation promote macrophages to escape mesoporous silica nanoparticle ( MSN ) -induced NF-\u03baB-dependent inflammation?"
            ]
        },
        {
            "id": "task847-f3108c48d2d6402a8688c94c4ce6e05d",
            "input": "Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition.', 'For 12 weeks, rats were fed a diet containing either 50% WR or 50% refined rye (RR). The WR diet provided more fiber (+21%) and polyphenols (+29%) than the RR diet. Fat intake was the same in both diets and particularly involved similar amounts of essential (18-carbon) n-3 and n-6 LCFAs.', 'The WR diet significantly increased the 24-hour urinary excretion of polyphenol metabolites-including enterolactone-compared with the RR diet. The WR rats had significantly more n-3 LCFA-in particular, eicosapentanoic (EPA) and docosahexanoic (DHA) acids-in their plasma and liver. Compared with the RR diet, the WR diet brought significant changes in gut microbiota composition, with increased diversity in the feces (Shannon and Simpson indices), decreased Firmicutes/Bacteroidetes ratio and decreased proportions of uncultured Clostridiales cluster IA and Clostridium cluster IV in the feces. In contrast, no difference was found between groups with regards to cecum microbiota. The WR rats had lower concentrations of total short-chain fatty acids (SCFA) in cecum and feces (p<0.05). Finally, acetate was lower (p<0.001) in the cecum of WR rats while butyrate was lower (p<0.05) in the feces of WR rats.",
            "output": [
                "Does whole Rye Consumption improve Blood and Liver n-3 Fatty Acid Profile and Gut Microbiota Composition in Rats?"
            ]
        },
        {
            "id": "task847-c11f92b7d81f46069c0d2b461142a7bb",
            "input": "In contrast to insulin-resistant individuals, insulin-sensitive athletes possess high intramyocellular lipid content (IMCL), good mitochondrial function and high perilipin 5 (PLIN5) levels, suggesting a role for PLIN5 in benign IMCL storage. We hypothesised a role for PLIN5 in modulating fasting-mediated insulin resistance.', 'Twelve men were fasted for 60\\xa0h, before and after which muscle biopsies were taken and stained for lipid droplets (LDs), PLIN5 and laminin. Confocal microscopy images were analysed for LD size, number, PLIN5 association and subcellular distribution.', 'Fasting elevated IMCL content 2.8-fold and reduced insulin sensitivity (by 55%). Individuals with the most prominent increase in IMCL showed the least reduction in insulin sensitivity (r\\u2009=\\u20090.657; p\\u2009=\\u20090.028) and mitochondrial function (r\\u2009=\\u20090.896; p\\u2009=\\u20090.006). During fasting, PLIN5 gene expression or PLIN5 protein content in muscle homogenates was unaffected, microscopy analyses revealed that the fraction of PLIN5 associated with LDs (PLIN5+) increased significantly (+26%) upon fasting, suggesting PLIN5 redistribution. The significant increase in LD number (+23%) and size (+23%) upon fasting was entirely accounted for by PLIN5+ LDs, not by LDs devoid of PLIN5. Also the association between IMCL storage capacity and insulin resistance and mitochondrial dysfunction was only apparent for PLIN5+ LDs.",
            "output": [
                "Does decoration of intramyocellular lipid droplets with PLIN5 modulate fasting-induced insulin resistance and lipotoxicity in humans?"
            ]
        },
        {
            "id": "task847-1994aa01262746688d6c533134b033ae",
            "input": "The aim of this study is to investigate the prognostic relevance of the best objective response of metastatic target lesions during sunitinib treatment in patients with metastatic renal cell carcinoma.', 'Radiographic analysis of the best objective response according to the Response Evaluation Criteria in Solid Tumors was assessed in 50 patients. Clinicopathological characteristics including the Heng risk classification and sunitinib-related adverse reactions were compared among four patient subgroups [complete response or partial response (CR/PR), stable disease (SD), progressive disease (PD), and those without treatment evaluation (NE)]. Kaplan-Meier and Cox proportional regression analyses of progression-free survival and overall survival were performed to identify prognostic variables.', 'The best objective response was CR/PR in 12 (24\\xa0%) patients, SD in 22 (44\\xa0%), PD in 6 (12\\xa0%), and NE in 10\\xa0(20\\xa0%). The incidence of hypertension and hypothyroidism was associated with a better objective response. Progression-free survival was 15.0, 9.2, 6.8, and 2.2\\xa0months in the CR/PR, SD, PD, and NE groups, respectively (P\\xa0=\\xa00.0004, log-rank test), while the corresponding median overall survival was 59.7, 24.2, 17.1, and 18.1\\xa0months, respectively (P\\xa0=\\xa00.007). Multivariate analysis revealed that hazard ratios for risk of death of the SD, PD, and NE groups were 4.51 (P\\xa0=\\xa00.06), 7.93 (P\\xa0=\\xa00.02), and 4.88 (P\\xa0=\\xa00.04), respectively, as compared to the CR/PR group.",
            "output": [
                "Are the best objective response of target lesions and the incidence of treatment-related hypertension associated with the survival of patients with metastatic renal cell carcinoma treated with sunitinib : a Japanese retrospective study?"
            ]
        },
        {
            "id": "task847-89c76326e49f4df89060e587e7cd48b5",
            "input": "An imbalance of excitatory and inhibitory neurotransmission underlies the glutamate hypothesis of schizophrenia. Agonists of group II metabotropic glutamate receptors, mGluR2/3, have been proposed as novel therapeutic agents to correct this imbalance. However, the influence of mGluR2/3 activity on excitatory and inhibitory neurotransmitter receptors has not been explored.', 'We aimed to investigate the ability of a novel mGluR2/3 agonist, LY379268, to modulate the availability of the excitatory N-methyl-D-aspartate receptor (NMDA-R) and the inhibitory gamma-aminobutyrate-A receptor (GABAA-R), in a two-hit mouse model of schizophrenia.', 'Wild type (WT) and heterozygous neuregulin 1 transmembrane domain mutant mice (NRG1 HET) were treated daily with phencyclidine (10 mg/kg ip) or saline for 14 days. After a 14-day washout, an acute dose of the mGluR2/3 agonist LY379268 (3 mg/kg), olanzapine (antipsychotic drug comparison, 1.5 mg/kg), or saline was administered. NMDA-R and GABAA-R binding densities were examined by receptor autoradiography in several schizophrenia-relevant brain regions.', 'In both WT and NRG1 HET mice, phencyclidine treatment significantly reduced NMDA-R and GABAA-R binding density in the prefrontal cortex, hippocampus, and nucleus accumbens. Acute treatment with LY379268 restored NMDA-R and GABAA-R levels in the two-hit mouse model comparable to olanzapine.",
            "output": [
                "Does mGluR2/3 agonist LY379268 rescue NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia?"
            ]
        },
        {
            "id": "task847-dd00e7bbed544303b6e4f944c8390daa",
            "input": "The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos.', 'We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model.', 'We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of HOX genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival.",
            "output": [
                "Are hOX transcription factors potential targets and markers in malignant mesothelioma?"
            ]
        },
        {
            "id": "task847-f4a792b7376a4c2eab6f16885ca762ae",
            "input": "Population-referenced total activity counts per day (TAC/d) percentiles provide public health practitioners a standardized measure of physical activity (PA) volume obtained from an accelerometer that can be compared across populations. The purpose of this study was to describe the application of TAC/d population-referenced percentiles to characterize the PA levels of population groups relative to US estimates.', 'A total of 679 adults participating in the 2011 NYC Physical Activity Transit survey wore an ActiGraph accelerometer on their hip for seven consecutive days. Accelerometer-derived TAC/d was classified into age- and gender-specific quartiles of US population-referenced TAC/d to compare differences in the distributions by borough (N=5).', 'Males in Brooklyn, Manhattan, and Staten Island had significantly greater TAC/d than US males. Females in Brooklyn and Queens had significantly greater levels of TAC/d compared to US females. The proportion of males in each population-referenced TAC/d quartile varied significantly by borough (\u03c7(2)(12)=2.63, p=0.002), with disproportionately more men in Manhattan and the Bronx found to be in the highest and lowest US population-referenced TAC/d quartiles, respectively. For females, there was no significant difference in US population-reference TAC/d quartile by borough (\u03c7(2)(12)=1.09, p=0.36).",
            "output": [
                "Does use of population-referenced total activity count percentiles to assess and classify physical activity of population groups?"
            ]
        },
        {
            "id": "task847-5e83d8d129994cf391f8a014c8064554",
            "input": "Endoscopic resection is becoming a well-established treatment option for patients with colloid cysts of the third ventricle. A disadvantage of this approach is the decreased ability to resect cysts in their entirety. Correlations between magnetic resonance imaging (MRI) features and cyst content could potentially help surgeons decide on the extent of resection and approach. We attempted to identify a correlation between patients' MRI imaging patterns and difficult cyst removal, post-operative adverse outcomes and the need for cerebrospinal fluid (CSF) diversion, in order to detect markers that may affect pre-surgical planning.\", \"A retrospective examination of all patients' records that underwent a colloid cyst excision attempt at our institution between 2001 and 2014, and which had a minimum 1-year follow-up was compiled.\", 'Of the 25 patients fulfilling the criteria, we found cysts with a low T2 signal, specifically when combined with high T1 signal, to be significantly correlated with piecemeal, difficult removals. Correlation was also found between high T2 signal cysts and pre-operative hydrocephalus. Among patients that had pre-existing hydrocephalus, those that required a piecemeal removal possessed a strong trend towards a need for subsequent shunting.",
            "output": [
                "Do mRI features have a role in pre-surgical planning of colloid cyst removal?"
            ]
        },
        {
            "id": "task847-26aafbc4c24f4b5f88fb371ef6413ada",
            "input": "Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia-reperfusion murine myocardial infarction model.', 'Mice underwent ischemia-reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging.', 'The mean size of the liposomes was 100nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163\u00b131% vs. 13\u00b114%, p=0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium.",
            "output": [
                "Does multimodality imaging demonstrate trafficking of liposomes preferentially to ischemic myocardium?"
            ]
        },
        {
            "id": "task847-615cc9be3385422b888e6e1231cd838b",
            "input": "Apoptosis plays a central role in maintaining the normal cell number and tissue homeostasis. Endophilins are a family of evolutionarily conserved proteins that have the critical role in endocytosis. Here, we determined whether endophilin A2 (EndoII) contributes to hydrogen peroxide (H2O2)-induced apoptosis in rat basilar artery smooth muscle cells (BASMCs) and the underlying mechanisms.', 'By using small interference RNA (siRNA) and EndoII overexpression strategy, we found that EndoII siRNA knockdown reduced cell viability and promoted H2O2-induced cell apoptosis, evidenced by loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9, 3 and poly (ADP-ribose) polymerase (PARP). In contrast, EndoII overexpression showed opposite effects and inhibited H2O2-induced BASMCs apoptosis. Further studies revealed that there was a direct interaction between EndoII and Bax. Upon H2O2-induced apoptosis, the association of EndoII with Bax were significantly decreased, while the interaction of Bax/tBid were increased, accompanied by a translocation of Bax from cytosol to mitochondria. Knockdown of EndoII did not affect the expression of Bax, but further promoted the binding of Bax with tBid and favored the accumulation of Bax to mitochondria as well as Bax activation; whereas EndoII overexpression produced the opposite effects. In addition, EndoII siRNA aggravated, but EndoII overexpression alleviated, the reduction of Bcl-2 expression in H2O2-treated cells.",
            "output": [
                "Does endophilin A2 protect H2O2-induced apoptosis by blockade of Bax translocation in rat basilar artery smooth muscle cells?"
            ]
        },
        {
            "id": "task847-a2b40c2295274549ae2091f28155c1af",
            "input": "Balance and maintaining postural equilibrium are important during stationary and dynamic movements to prevent falls, particularly in older adults. While our sense of balance is influenced by vestibular, proprioceptive, and visual information, this study focuses primarily on the vestibular component and its age-related effects on balance. C57Bl/6J mice of ages 1, 5-6, 8-9 and 27-28 months were tested using a combination of standard (such as grip strength and rotarod) and newly-developed behavioral tests (including balance beam and walking trajectory tests with a vestibular stimulus). In the current study, we confirm a decline in fore-limb grip strength and gross motor coordination as age increases. We also show that a vestibular stimulus of low frequency (2-3 Hz) and duration can lead to age-dependent changes in balance beam performance, which was evident by increases in latency to begin walking on the beam as well as the number of times hind-feet slip (FS) from the beam. Furthermore, aged mice (27-28 months) that received continuous access to a running wheel for 4 weeks did not improve when retested. Mice of ages 1, 10, 13 and 27-28 months were also tested for changes in walking trajectory as a result of the vestibular stimulus. While no linear relationship was observed between the changes in trajectory and age, 1-month-old mice were considerably less affected than mice of ages 10, 13 and 27-28 months.",
            "output": [
                "Is motor Performance Impaired Following Vestibular Stimulation in Ageing Mice?"
            ]
        },
        {
            "id": "task847-f4afa91d00c74d5eb4cfab006135f4f0",
            "input": "Elevated levels of cardiometabolic markers are characteristic of normal pregnancy, however, insulin resistance and increased glucose, triglyceride, and cholesterol levels can adversely influence maternal and child health. Diet is a modifiable behaviour that could have significant impact on maternal cardiometabolic levels during pregnancy. We investigated the association between dietary patterns and cardiometabolic markers (glucose, insulin, insulin resistance (HOMA-IR), triglycerides, and cholesterol) during pregnancy.', 'Data from the Pregnancy, Infection, and Nutrition prospective cohort study (2000-05) was used (n = 513). Diet was assessed using a food frequency questionnaire. Dietary patterns were derived using latent class analysis (LCA) and the Dietary Approaches to Stop Hypertension (DASH) diet. Linear regression was used to examine the dietary patterns-cardiometabolic markers association during pregnancy.', 'Three dietary patterns evolved from the LCA characterised by high intakes of: (1) hamburgers, hot dogs, bacon, French fries, fried chicken, white bread, and soft drinks; (2) some vegetables, fruit juice, refined grains, mixed dishes, processed meat, and empty calorie foods; and (3) fruits, vegetables, whole grains, low-fat dairy, breakfast bars, and water. After adjustment for potential confounders including prepregnancy body mass index, a diet consistent with Latent Class 3 was negatively associated with maternal insulin (\u03bcU/mL: \u03b2 = -0.12; 95% CI -0.23, -0.01) and HOMA-IR (\u03b2 = -0.13; 95% CI -0.25, -0.00). Additionally, DASH scores within Tertile 3 (higher dietary quality) were also negatively associated with maternal triglycerides (mg/dL).",
            "output": [
                "Are maternal Dietary Patterns Associated with Lower Levels of Cardiometabolic Markers during Pregnancy?"
            ]
        },
        {
            "id": "task847-b65a1119cd594c04990c8f0a59a44160",
            "input": "Zidovudine (AZT) is mainly used to prevent mother-to-child HIV-1 transmission (PMTCT). Despite serious concerns on AZT-associated toxicity, there is little information on pharmacokinetics of intracellular AZT metabolites in infants.', 'We conducted a prospective study in 31 HIV-uninfected infants who received AZT for PMTCT. Blood samples were obtained from 14 infants on postdelivery days (PDD) 1, 7, 14, and 28 and from 17 infants at 0 and 4 hours after dosing on PDD-1. Plasma AZT concentrations (pAZT) and intracellular concentrations of AZT-monophosphate (icAZT-MP), diphosphate (icAZT-DP), and triphosphate (icAZT-TP) were determined.', 'Plasma AZT and icAZT-MP concentrations were 2713 nmol/L and 79 fmol/10 cells in PDD-1, but decreased to 1437 nmol/L and 31 fmol/10 cells by PDD-28 (P = 0.02 and P = 0.07 for all PDDs, respectively), whereas those of icAZT-DP and icAZT-TP remained low throughout the sampling period (P = 0.29 and P = 0.61 for all PDDs, respectively) There were no differences in icAZT-TP between infants of the 2 mg/kg 4 times a day dose and 4 mg/kg twice daily dose (P = 0.25), whereas pAZT and icAZT-MP levels were higher in the latter (P < 0.01 and <0.01, respectively). The pAZT and icAZT-MP significantly increased from 0 to 4 hours after dosing (P < 0.001 and <0.001, respectively), whereas icAZT-DP, icAZT-TP levels were not changed (P = 0.41 and 0.33, respectively).",
            "output": [
                "Do high Plasma Concentrations of Zidovudine ( AZT ) Parallel Intracellular Concentrations of AZT-Triphosphates in Infants During Prevention of Mother-to-Child HIV-1 Transmission?"
            ]
        },
        {
            "id": "task847-8aab81e417ef4c59a91b59f77ffc7d10",
            "input": "To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model.', 'An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist.', 'Tertiary medical center and school of medicine laboratory.', 'Laboratory animals-rabbits.', 'Balloon obstruction of infrarenal aorta introduced via femoral artery incision.', 'Severe hindlimb paralysis (mean Tarlov score 0.36\u00b10.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58\u00b10.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001).",
            "output": [
                "Does minocycline Effectively protect the Rabbit 's Spinal Cord From Aortic Occlusion-Related Ischemia?"
            ]
        },
        {
            "id": "task847-b812df07619c436eace5bba03a79237a",
            "input": "To investigate the role of nitric oxide (NO)-induced autophagy in human dental pulp cells (HDPCs) and the involvement of AMP-activated protein kinase (AMPK) pathway.', \"The MTT assay was used to determine the cytotoxic effect of the NO donor sodium nitroprusside (SNP) in HDPCs. Apoptosis was detected by means of the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and apoptosis- or autophagy-related signal molecules were observed by Western blot analysis. Acidic autophagolysosomal vacuoles were stained with acridine orange to detect autophagy in the presence of 3-methyladenine (3MA) used to inhibit autophagy. To explore the mechanism underlying autophagy and its protective role against apoptosis, compound C, the chemical AMPK inhibitor, was used. Statistical analysis was performed using Student's t-test or analysis of variance (ANOVA) followed by the Student-Newman-Keuls test (p<0.05).\", 'SNP decreased viability of the HDPCs in a dose- and time-dependent manner. Exposing the HDPCs to SNP increased the levels of p62 and LC3-II, the typical markers of autophagy, and increased the number of acidic autophagolysosomal vacuoles, indicating the appearance of autophagy as detected by acridine orange staining (p<0.05). Pretreatment with 3MA decreased cell viability but increased cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3, apoptosis indicators, in the SNP-treated HDPCs (p<0.05). SNP activated AMPK/ULK signaling, while the inhibition of AMPK by compound C enhanced apoptotic cell death induced by SNP in the HDPCs (p<0.05).",
            "output": [
                "Do nitric oxide-induced autophagy and the activation of AMPK pathway protect against apoptosis in human dental pulp cells?"
            ]
        },
        {
            "id": "task847-b88aa9798ad84f2eb1e71bab69b93a20",
            "input": "We sought to determine the relative lipase production of a range of ocular bacterial isolates and to assess the efficacy of glycerol monolaurate (GML) in inhibiting this lipase production in high lipase-producing bacteria without affecting bacterial cell growth.', 'Staphylococcus aureus,Staphylococcus epidermidis,Propionibacterium acnes, and Corynebacterium spp. were inoculated at a density of 10(6)/mL in varying concentrations of GML up to 25 \u03bcg/mL for 24 hours at 37 \u00b0C with constant shaking. Bacterial suspensions were centrifuged, bacterial cell density was determined, and production of bacterial lipase was quantified using a commercial lipase assay kit.', 'Staphylococcus spp. produced high levels of lipase activity compared with P. acnes and Corynebacterium spp. GML inhibited lipase production by Staphylococcal spp. in a dose-dependent manner, with S. epidermidis lipase production consistently more sensitive to GML than S. aureus. Glycerol monolaurate showed significant (P < 0.05) lipase inhibition above concentrations of 15 \u03bcg/mL in S. aureus and was not cytotoxic up to 25 \u03bcg/mL. For S. epidermidis, GML showed significant (P < 0.05) lipase inhibition above 7.5 \u03bcg/mL.",
            "output": [
                "Does glycerol Monolaurate inhibit Lipase Production by Clinical Ocular Isolates Without Affecting Bacterial Cell Viability?"
            ]
        },
        {
            "id": "task847-abb5f11c800d4bf4a829da0e3106a15a",
            "input": "Incidence of renal cell carcinoma (RCC) is higher in Black patients with disease-specific and overall survival being lower compared with White patients even though renal tumors among Black patients are more likely to be localized. These disparities have been attributed to higher rates of obesity and hypertension, lower rates of nephrectomy, and a lack of access to quality health care. With scant genomic evidence to account for these disparities, the present study sought to compare BAP1 expression between Black and White patients with clear cell RCC (ccRCC); a gene that inhibits tumor progression when overexpressed and results in poor clinical outcomes when silenced.', 'The cancer genome atlas dataset was used to identify 58 (9.9%) Black and 529 (90.9%) White patients with ccRCC with an initial pathologic diagnosis from 1998 to 2013. BAP1 expression was compared using a Mann-Whitney U test. The association between BAP1 expression and pathologic stage, American Joint Committee on Cancer (AJCC) stage, and Fuhrman grade was assessed for the overall cohort and stratified by race. The association between BAP1 expression and overall survival was assessed using Cox proportion hazards models adjusting for Fuhrman grade, pathologic stage, and the presence of pathologic metastases for the overall cohort and stratified by race.', 'The level of BAP1 expression was significantly higher in Black vs. White patients with ccRCC (10.5 vs. 10.3; P<.001). For the overall cohort, increasing BAP1 expression was associated with decreasing pathologic stage (\u03b2 =-0.25, P = .004) and decreasing AJCC stage (\u03b2 =-0.029, P = .006). For Black patients, increasing BAP1 expression was associated with decreasing AJCC stage (\u03b2 =-0.79, P = .016), decreasing Fuhrman grade (\u03b2 =-0.55, P = .011), and a decreased risk of pathologic metastases (odds ratio [OR] = 0.83, P = .038). For White patients, increasing BAP1 expression was associated with decreasing pathologic stage (\u03b2 =-0.20, P = .026).",
            "output": [
                "Is bAP1 overexpressed in black compared with white patients with Mx-M1 clear cell renal cell carcinoma : A report from the cancer genome atlas?"
            ]
        },
        {
            "id": "task847-186c235032f34188a92a3c267ecdefd0",
            "input": "Lymph node size as a prognostic parameter has not been investigated well in the past. Recent data, however, have indicated that this parameter could be even more important than the lymph node count.', 'Based on the results of earlier studies, we analyzed the lymph node size and number of node-negative colon cancer patients with regard to survival. Data from 115 node-negative cases of colon cancer were analyzed. Lymph nodes with diameters \u22645 mm were defined as small, and all other lymph nodes were classified as intermediate/large in size and labeled LN5. All of the cases were categorized according to the number of LN5s. The LN5 very low (LN5vl) group included cases with less than two LN5s. All of the other cases were assigned to the LN5 low/high (LN5l/h) group.', 'The overall survival analysis revealed significantly worse outcomes for the LN5vl group, with a mean survival of 34 months compared to the LN5l/h group, with a mean survival of 40 months (P\\u2009=\\u20090.022). After adjusting for the pT1/2 and pT3/4 stages, we still found a significant outcome difference (P\\u2009=\\u20090.012). Multivariate analysis identified LN5vl and T-stage as being independently correlated with the outcome. The vast majority of LN5vl cases (91 %) were located in the left colon. The location itself, however, was not prognostic (P\\u2009=\\u20090.478).",
            "output": [
                "Is lymph node hypoplasia associated with adverse outcomes in node-negative colon cancer using advanced lymph node dissection methods?"
            ]
        },
        {
            "id": "task847-557824a3522044c6983668986ea3b95f",
            "input": "Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB)-induced right heart failure model and investigated whether cardiac output (CO) is responsible for the progression of hepatic fibrosis.', 'Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2\u00b127.6 and 150.1\u00b131.2 ml/min, P<0.01). Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8\u00b11.7 and 1.0\u00b10.2%, P<0.01, 76.2\u00b127.5 and 32.7\u00b17.5 ng/ml, P<0.01). Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1\u03b1 positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-\u03b21, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2) were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1\u03b1 was significantly increased in the PAB group than that in the control group (2.31\u00b10.84 and 1.0\u00b10.18 arbitrary units, P<0.05).",
            "output": [
                "Does low Cardiac Output lead Hepatic Fibrosis in Right Heart Failure Model Rats?"
            ]
        },
        {
            "id": "task847-c2645f685c3c4859b168b2ec7057a6d5",
            "input": "The lumbar ligamentum \ufb02avum (LF) is an important part of the spine to maintain the stability of the spine. In this study we aimed to examine whether mechanical force by cyclic stretch could induce apoptosis in human LF cells and investigate the underlying mechanism.', 'LF cells were isolated from six young patients undergoing spinal surgery and then cultured in vitro. LF cells were subjected to cyclic stretch and the poptosis was detected by flow cytometry. The level of intracellular reactive oxygen species (ROS) and caspase-9 activity were measured.', 'Cyclic stretch at a frequency of 0.5\\u2005Hz with 20% elongation induced the apoptosis of human LF cells in vitro, and this was correlated with increased ROS generation and activation of caspase-9.",
            "output": [
                "Does cyclic stretch enhance apoptosis in human lumbar ligamentum \ufb02avum cells via the induction of reactive oxygen species generation?"
            ]
        },
        {
            "id": "task847-b295d3bdbc8d43f0ae0393b6c9a4305f",
            "input": "Pedicle subtraction osteotomy (PSO) is one of the surgical options for treating alignment disorders of the fused spine (due to post-surgical fusion or related to arthritis). It enables satisfactory sagittal realignment and improved function due to economic sagittal balance. The aim of this study was to analyze clinical and radiological results of PSO after a minimum follow-up of 2\\xa0years and demonstrate the benefit of sub-group analysis as a function of pelvic incidence (PI).', 'A descriptive prospective single center study of 63 patients presenting with spinal global malalignment who underwent correction by PSO. Function was assessed by the Oswestry disability index (ODI), a visual analog scale of lumbar pain (VAS) and a SF-36 questionnaire. Radiographic analyses of pre- and post-operative pelvic-spinal parameters were performed on X-rays obtained by EOS(\u00ae) imaging after 3D modeling. Global analysis and analysis of sub-groups as a function of pelvic incidence were performed and the full balance integrated index (FBI) was calculated.', 'this series showed a marked clinical improvement and significant progress of functional scores. Global post-operative radiological analysis showed a significant improvement in all pelvic and spinal parameters. The mean correction obtained after PSO was 31.7\u00b0\\xa0\u00b1\\xa08.4\u00b0, hence global improvement of lumbar lordosis of 22\u00b0. The sagittal vertical angle (SVA) decreased from +9\\xa0cm before surgery to +4.3\\xa0cm after surgery. Sub-group analysis demonstrated greater improvement in pelvic tilt, sacral slope and spinal parameters of patients with a small or moderate pelvic incidence; all had an FBI index\\xa0<10\u00b0. Most of the pelvic and spinal parameters of patients with a large pelvic incidence were insufficiently corrected and they had an FBI index\\xa0>10\u00b0",
            "output": [
                "Are clinical and radiological outcomes of lumbar posterior subtraction osteotomies correlated to pelvic incidence and FBI index : Prospective series of 63 cases?"
            ]
        },
        {
            "id": "task847-785156589a5a4ed597c4f7c0ac10126a",
            "input": "The soluble factors secreted by mesenchymal stem cells are thought to either support or inhibit tumor growth. Herein, we investigated whether the human lung-derived mesenchymal stem cell-conditioned medium (hlMSC-CM) exerts antitumor activity in malignant pleural mesothelioma cell lines H28, H2052 and Meso4.', 'hlMSC-CM was collected from the human lung-derived mesenchymal stem cells. Inhibition of tumor cell growth was based on the reduction of cell viability and inhibition of cell proliferation using the XTT and BrdU assays, respectively. Elimination of tumor spheroids was assessed by the anchorage-independent sphere formation assay. The cytokine profile of hlMSC-CM was determined by a chemiluminescence-based cytokine array.', 'Our data showed that hlMSC-CM contains a broad range of soluble factors which include: cytokines, chemokines, hormones, growth and angiogenic factors, matrix metalloproteinases, metalloproteinase inhibitors and cell-cell mediator proteins. The 48- and 72-hour hlMSC-CM treatments of H28, H2052 and Meso4 cell lines elicited significant decreases in cell viability and inhibited cell proliferation. The 72-hour hlMSC-CM incubation of H28 cells completely eliminated the drug-resistant sphere-forming cells, which is more potent than twice the half maximal inhibitory concentration of cisplatin.",
            "output": [
                "Does human lung-derived mesenchymal stem cell-conditioned medium exert in vitro antitumor effects in malignant pleural mesothelioma cell lines?"
            ]
        },
        {
            "id": "task847-5f2cdab56e224995a9ee33c2fc9c28df",
            "input": "The pyronaridine-artesunate combination is one of the most recent oral artemisinin-based therapeutic combinations (ACTs) recommended for the treatment of uncomplicated P. falciparum malaria. The emergence of P. falciparum resistance to artemisinin has recently developed in Southeast Asia. Little data are available on the association between pyronaridine susceptibility and polymorphisms in genes involved in antimalarial drug resistance. The objective of the present study was to investigate the association between ex vivo responses to pyronaridine and the K76T mutation in the pfcrt gene in P. falciparum isolates.', 'The assessment of ex vivo susceptibility to pyronaridine was performed on 296 P. falciparum isolates using a standard 42-h 3H-hypoxanthine uptake inhibition method. The K76T mutation was also investigated.', 'The pyronaridine IC50 (inhibitory concentration 50 %) ranged from 0.55 to 80.0 nM. Ex vivo responses to pyronaridine were significantly associated with the K76T mutation (p-value\\u2009=\\u20090.020). The reduced susceptibility to pyronaridine, defined as IC50\\u2009>\\u200960 nM, was significantly associated with the K76T mutation (p-value\\u2009=\\u20090.004). Using a Bayesian mixture modelling approach, the pyronaridine IC50 were classified into three components: component A (IC50 median 15.9 nM), component B (IC50 median 34.2 nM) and component C (IC50 median 63.3 nM). The K76T mutation was represented in 46.3% of the isolates in component A, 47.2% of the isolates in component B and 73.3% of the isolates in component C (p-value\\u2009=\\u20090.021).",
            "output": [
                "Is the Plasmodium falciparum chloroquine resistance transporter associated with the ex vivo P. falciparum African parasite response to pyronaridine?"
            ]
        },
        {
            "id": "task847-4e9abebed9484bc686c676328890d471",
            "input": "We hypothesised that abnormal global longitudinal strain (GLS) would predict outcome in hypertrophic cardiomyopathy (HCM) better than current echocardiographic measures.', 'Retrospective analysis of risk markers in relation to outcomes in 472 patients with HCM at a single tertiary institution (2006-2012). Exclusion criteria were left ventricular (LV) hypertrophy of other origin, patients in atrial fibrillation, lost to follow-up and insufficient image quality to perform strain analysis. Standardised echocardiogram recordings were reviewed and standard variables and LV GLS were measured. The primary end-point included all cardiac deaths, appropriate defibrillator shocks and heart failure (HF) admissions. The secondary end-point was death by HF and admissions related to HF.', \"Mean age was 50.0\u00b115.0\\u2005years; 322 (68%) were men. At a median of 4.3\\u2005years (IQR 0.1-7.8) follow-up, 21 (4.4%) patients experienced cardiovascular death: 6 (1.3%) died from HF, 13 (2.7%) had sudden cardiac death and 2 (0.4%) died secondary to stroke. Four (0.8%) patients experienced appropriate defibrillator shock, and 13 (2.7%) were admitted for HF. On multivariate Fine-Gray proportional hazard analyses, GLS was significantly associated with the primary end-point (HR=0.90, 95% CI 0.83 to 0.98, p=0.018) independently of age, maximal provoked LV outflow-tract gradient and LV end-systolic volume. Moreover, GLS was particularly associated with the secondary end-point (HR=0.82, 95% CI 0.75 to 0.90, p<0.0001) independently of age, previous atrial fibrillation, New York Heart Association (NYHA) class III-IV, LV end-systolic volume, E/E', and outflow-tract gradient. Survival curves confirmed that GLS was associated with HF events (GLS <15.6%, p=0.0035).",
            "output": [
                "Is global longitudinal strain associated with heart failure outcomes in hypertrophic cardiomyopathy?"
            ]
        },
        {
            "id": "task847-85a4a08e9807477bba0d217a462616b6",
            "input": "There are few studies of quality interventions to mitigate the risk of transfusion-associated circulatory overload (TACO). Our aim was to reduce TACO risk in patients admitted to internal medicine at our hospital, by addressing gaps in transfusion practice.', 'A 3-month baseline audit of red blood cell (RBC) transfusion orders was conducted. An intervention consisting of a transfusion order set and physician checklist was developed and implemented based on identified gaps, followed by a 3-month post-intervention audit. Compliance with appropriateness criteria for RBC transfusion was ascertained, along with documentation of transfusion rate, diuretic usage and consent.', 'A total of 97 transfusion orders from 68 inpatients and 95 orders from 62 inpatients were audited in the baseline and post-intervention groups, respectively. Compliance with appropriateness criteria was similar pre- and post-intervention (87 versus 85%, P = 0\u00b781). Specification of transfusion rate improved (84 versus 98%, P < 0\u00b701), and diuretics were appropriately ordered more frequently for patients with TACO risk factors (37 versus 64%, P < 0\u00b701). Timing of diuretics shifted from between or post-transfusion to pre-transfusion (35 versus 86%, P < 0\u00b701), without increases in hypokalemia or acute kidney injury. No case of TACO was observed during the study. Documentation of specific risks discussed during consent discussion improved (4 versus 23%, P < 0\u00b701).",
            "output": [
                "Do an order set and checklist improve physician transfusion ordering practices to mitigate the risk of transfusion-associated circulatory overload?"
            ]
        },
        {
            "id": "task847-7ed4431403da4c22807e28440b2f6b56",
            "input": "The critical issue related to breast-conserving therapy (BCT) is that cosmetic outcomes deteriorate with long-term follow-up. There is little research for breast density as a predictor of cosmetic outcomes at the late stage after BCT. To improve the long-term quality of life after BCT of breast cancer patients, the correlation of volumetric breast density (VBD) and cosmetic outcome at the late stage after BCT was evaluated.', 'Breast volume, fibroglandular tissue volume, adipose tissue volume, and VBD were calculated on mammography using image analysis software (Volpara(\u00ae)) in 151 patients with BCT. Furthermore, the correlation of breast density and the change of breast volume over time was analyzed on mammography in 99 patients who were followed-up long-term after BCT.', 'On multivariate analysis, VBD was a predictor of cosmetic outcome after BCT with percent breast volume excised (PBVE). Decreased adipose tissue volume and increased fibrosis were more common in patients with VBD < 15%. Furthermore, remnant breast volume continued to decrease over time in low breast density patients during long-term follow-up. 93% of patients with VBD \u2265 15% and PBVE < 10% had a better cosmetic outcome, while 60% of patients with VBD < 15% and PBVE \u2265 10% had a worse cosmetic outcome after BCT.",
            "output": [
                "Is volumetric breast density essential for predicting cosmetic outcome at the late stage after breast-conserving surgery?"
            ]
        },
        {
            "id": "task847-3fe7de7690f649b9ba37b8372eeabb90",
            "input": "Lubricin expression in the superficial cartilage will be a crucial factor in the success of cartilage regeneration. Mesenchymal stem cells (MSCs) are an attractive cell source and the use of aggregates of MSCs has some advantages in terms of chondrogenic potential and efficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elucidated so far. Our goals were to determine (1) whether cartilage pellets of human MSCs expressed lubricin in vitro chondrogenesis, (2) whether aggregates of human MSCs promoted lubricin expression, and (3) whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats.', 'For in vitro analysis, human bone marrow (BM) MSCs were differentiated into cartilage by pellet culture, and also aggregated using the hanging drop technique. For an animal study, aggregates of BM MSCs derived from GFP transgenic rats were transplanted to the osteochondral defect in the trochlear groove of wild type rat knee joints. Lubricin expression was mainly evaluated in differentiated and regenerated cartilages.', 'In in vitro analysis, lubricin was detected in the superficial zone of the pellets and conditioned medium. mRNA expression of Proteoglycan4 (Prg4), which encodes lubricin, in pellets was significantly higher than that of undifferentiated MSCs. Aggregates showed different morphological features between the superficial and deep zone, and the Prg4 mRNA expression increased after aggregate formation. Lubricin was also found in the aggregate. In a rat study, articular cartilage regeneration was significantly better in the MSC group than in the control group as shown by macroscopical and histological analysis. The transmission electron microscope showed that morphology of the superficial cartilage in the MSC group was closer to that of the intact cartilage than in the control group. GFP positive cells remained in the repaired tissue and expressed lubricin in the superficial cartilage.",
            "output": [
                "Does cartilage Derived from Bone Marrow Mesenchymal Stem Cells express Lubricin In Vitro and In Vivo?"
            ]
        },
        {
            "id": "task847-0ed81383fd2d42009face592f4ada555",
            "input": "Although aminosalicylic acid (ASA) preparations have been used as first-line drugs for the treatment of ulcerative colitis (UC), no consistent view has been established regarding the ASA dose during the remission-maintenance phase of the disease. In this study, we examined whether the ASA dose should be reduced during the remission-maintenance phase.', 'This study included 203 patients in the remission-maintenance phase of UC. The Mayo endoscopic subscore (MES) was used to evaluate mucosa. Comparison and analysis were performed between patients whose ASA dose had been unchanged and whose dose had been reduced, between patients with endoscopic healing (EH) group and those without endoscopic healing (WEH) group, and between patients with an MES of 0 and 1.', 'Comparison between the unchanged-ASA and reduced-ASA groups revealed that the remission-maintenance rate was higher in the unchanged-ASA group (p\\u2009<\\u20090.001). Next, the remission-maintenance rate was higher in the EH/unchanged-ASA group than in the EH/reduced-ASA group (p\\u2009=\\u20090.042). Comparison between the MES 0 and 1 groups revealed that the remission-maintenance rate was higher in the MES 0 group (p\\u2009=\\u20090.007). In addition, no significant difference in remission-maintenance rates was observed between the MES 0/unchanged-ASA group and the MES 0/reduced-ASA group (p\\u2009=\\u20090.108).",
            "output": [
                "Does timing for dose-down of 5-ASA depend on mucosal status with ulcerative colitis?"
            ]
        },
        {
            "id": "task847-5e93687f92b84750839147200c83f187",
            "input": "Long-term prognosis of hepatocellular carcinoma (HCC) patients is challenging, and novel biomarkers are needed to predict patient risk and serve as potential therapeutic target.', 'We found \u03b2-glucosidase 1 is significantly overexpressed and activated in primary HCC tissue and multiple HCC cell lines. \u03b2-Glucosidase 1 expression is associated with predicting prognosis of HCC patients under chemotherapy. Silencing \u03b2-glucosidase 1 inhibits growth and survival of HCC cells, with preferential inhibitory effects on high \u03b2-glucosidase 1-expressing cells. Combination of chemo drug with \u03b2-glucosidase 1 inhibitor sensitized HCC cells to chemotherapy.",
            "output": [
                "Is identification of \u03b2-glucosidase 1 as a biomarker and its high expression in hepatocellular carcinoma associated with resistance to chemotherapy drugs?"
            ]
        },
        {
            "id": "task847-d51ed41e27f24ca48586112be3aed912",
            "input": "BDNF blood levels are reduced in MDD. They can be increased with pharmacologic treatment and ECT, but it is not clear whether the combination of treatments promotes an additional increase. The present study aims to evaluate whether combined treatment promotes an increase in BDNF, restoring the level to that of non-depressed controls.', 'Ninety-nine adult inpatients were invited to participate in this naturalistic prospective cohort study between May 2011 and April 2013. Diagnosis was made by MINI, and the symptoms were evaluated at admission and at discharge by HDRS-17. Those inpatients with a diagnosis of depression were included and divided into two groups: those who underwent combined ECT and medication (31 subjects) and those who used only pharmacotherapy (68 subjects). Serum BDNF was measured in blood samples collected at admission and discharge. One hundred healthy blood donors without any psychiatric diagnosis were included as a control group.', 'There were no significant differences in serum BDNF levels between the combined and pharmacological groups at admission and at discharge, and no significant variation in BDNF occurred in any group during the treatment. There were no interactions between time and treatment groups nor significant time effects or treatment group effects for BDNF in the Generalized Estimating Equation Model (GEE). The control group had significantly higher serum BDNF levels in comparison with each of the treatment groups at admission and discharge (p = 0.00).",
            "output": [
                "Is combining ECT with pharmacological treatment of depressed inpatients in a naturalistic study associated with serum BDNF level increase?"
            ]
        },
        {
            "id": "task847-cde1b5d5535045dca05f7539ed5d95ad",
            "input": "Substance P (SP) is a neuropeptide known to enhance the swallow response. It likely acts as a neurotransmitter in the pharyngeal mucosa in response to local stimuli. It has been proposed that dysphagia after stroke may be related to reduced levels of SP, which therefore constitutes a therapeutic target. In the present pilot study, we evaluated whether electrical pharyngeal stimulation (EPS), a neuromodulation device to enhance cortical reorganization for the restoration of swallowing function after brain injury, is able to increase SP in saliva or serum.', 'In a randomized crossover study design, 20 healthy volunteers were treated with 10 min of real (0.2-ms pulses, 5 Hz, 280 V, stimulation intensity (mA) individually adjusted to tolerance level) or sham EPS on two separate sessions. Stimulation was delivered via a pair of bipolar ring electrodes mounted on an intraluminal catheter positioned in the pharynx. Blood and saliva samples were taken prior to, during, and up to 1 h after EPS and analyzed for their SP concentration by ELISA.', 'Following real EPS but not sham stimulation, SP levels in saliva increased immediately and significantly about 28% (p < 0.01) compared to baseline. Serum levels remained unchanged.",
            "output": [
                "Does electrical pharyngeal stimulation increase substance P level in saliva?"
            ]
        },
        {
            "id": "task847-e3361bc397b94a89a98b1bf860b422f4",
            "input": "Prenatal maternal lipopolysaccharide (LPS) exposure leads to behavioral deficits such as depression, anxiety, and schizophrenia in the adult lives. LPS-exposure resulted in the production of cytokines and oxidative damage. On the contrary, astaxanthin is a carotenoid compound, showed neuroprotective properties via its antioxidant capacity. This study examines the effect of astaxanthin on the prenatal maternal LPS-induced postnatal behavioral deficit in mice.', 'We found that prenatal LPS-exposed mice showed extensive immobile phase in the tail suspension test, higher frequent head dipping in the hole-board test and greater hypolocomotion in the open field test. All these values were statistically significant (p\\xa0<\\xa00.05). In addition, a marked elevation of the level of lipid peroxidation, advanced protein oxidation product, nitric oxide, while a pronounced depletion of antioxidant enzymes (superoxide dismutase, catalase and glutathione) were observed in the adult offspring mice that were prenatally exposed to LPS. To the contrary, 6-weeks long treatment with astaxanthin significantly improved all behavioral deficits (p\\xa0<\\xa00.05) and diminished prenatal LPS-induced oxidative stress markers in the brain and liver.",
            "output": [
                "Does astaxanthin ameliorate prenatal LPS-exposed behavioral deficits and oxidative stress in adult offspring?"
            ]
        },
        {
            "id": "task847-a1fee9b22b4a4c5baee996aa051137c4",
            "input": "BAF312 (Siponimod) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. This drug is currently undergoing clinical trials for the treatment of secondary progressive multiple sclerosis (MS). Here, we investigated the effects of BAF312 on isolated astrocyte and microglia cultures as well as in slice culture models of demyelination.', 'Mouse and human astrocytes were treated with S1PR modulators and changes in the levels of pERK, pAkt, and calcium signalling as well as S1PR1 internalization and cytokine levels was investigated using Western blotting, immunochemistry, ELISA and confocal microscopy. Organotypic slice cultures were prepared from the cerebellum of 10-day-old mice and treated with lysophosphatidylcholine (LPC), psychosine and/or S1PR modulators, and changes in myelination states were measured by fluorescence of myelin basic protein and neurofilament H.', 'BAF312 treatment of human and mouse astrocytes activated pERK, pAKT and Ca(2+) signalling as well as inducing S1PR1 internalization. Notably, activation of S1PR1 increased pERK and pAKT in mouse astrocytes while both S1PR1 and S1PR3 equally increased pERK and pAKT in human astrocytes, suggesting that the coupling of S1PR1 and S1PR3 to pERK and pAKT differ in mouse and human astrocytes. We also observed that BAF312 moderately attenuated lipopolysaccharide (LPS)- or TNF\u03b1/IL17-induced levels of IL6 in both astrocyte and microglia cell cultures. In organotypic slice cultures, BAF312 reduced LPC-induced levels of IL6 and attenuated LPC-mediated demyelination. We have shown previously that the toxic lipid metabolite psychosine induces demyelination in organotypic slice cultures, without altering the levels of cytokines, such as IL6. Importantly, psychosine-induced demyelination was also attenuated by BAF312.",
            "output": [
                "Does the dual S1PR1/S1PR5 drug BAF312 ( Siponimod ) attenuate demyelination in organotypic slice cultures?"
            ]
        },
        {
            "id": "task847-53d55a8a599f4cbd8c34c0a66aba4775",
            "input": "We designed an assessment and education program which was delivered to patients prior to first outpatient appointment for bariatric surgery. We hypothesised that this program would streamline care and would lead to improved weight loss following bariatric surgery.', 'The program incorporates a structured general practitioners (GP) review, a patient information evening and an on-line learning package. It was introduced in September 2012. Patient flow through the program was recorded. Outcomes of the new program were compared with contemporaneously treated patients who did not undertake the pre-hospital program.', 'All 636 patients on the waiting list for first appointment at the Alfred Health bariatric surgery clinic were invited to participate. There were 400 patients ultimately removed from the waiting list for first appointment. Of the remaining 236 patients, 229 consented to participate in the new program. The mean BMI was 47.8\\u2009\u00b1\\u20099.2. The fail to attend first appointment rate dropped from 12 to 2.1\\xa0%. At 12\\xa0months post-bariatric surgery, patients who undertook the new program (n\\u2009=\\u200982) had a mean excess weight loss (EWL) of 41.1\\u2009\u00b1\\u200920.3\\xa0% where as those treated on the standard pathway (n\\u2009=\\u200961) had a mean EWL 32\\u2009\u00b1\\u200918.0\\xa0% (p\\u2009=\\u20090.012).",
            "output": [
                "Does a Pre-Hospital Patient Education Program improve Outcomes of Bariatric Surgery?"
            ]
        },
        {
            "id": "task847-d16c058be01c479da89e485773807ccc",
            "input": "Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure. In patients without the option of lung transplantation, prognostication is challenging. We hypothesized that duration of ECMO therapy is inversely correlated with the chance of recovery and therefore hospital survival.', 'A single-center retrospective register analysis was performed. All bridge-to-recovery venovenous ECMO patients without option for lung transplantation treated between October 2010 and September 2015 were included.', 'A total of 175 patients (mean age, 51.61 \u00b1 2.11 years) were detected. Medium time on ECMO was 9.26 \u00b1 1.91 days. Time on ECMO was not significantly shorter in survivors compared to nonsurvivors (8.23 \u00b1 2.04 and 10.15 \u00b1 3.07, respectively; P = .327). Rate of hospital survival and time on ECMO did not correlate (P = .103). The predictive value of ECMO duration on hospital survival was 0.503 in a receiver operating characteristic analysis.",
            "output": [
                "Is duration of extracorporeal membrane oxygenation a poor predictor of hospital survival?"
            ]
        },
        {
            "id": "task847-e0b57683c32a4d2faba8183049ce5aad",
            "input": "We investigated whether high prolactin levels were associated with delirium in septic patients because neuropsychiatric disorders are frequently associated with hyperprolactinemia.', 'Prolactin levels were measured daily for 4 days in 101 patients with sepsis. Delirium was assessed using the Richmond Agitation Sedation Scale and the Confusion Assessment Method in the ICU.', 'Delirium developed in 79 patients (78%) and was more common in patients older than 65 years. Prolactin levels were higher in patients with delirium than in those without over the 4 days of observation (P = .032). In patients with delirium, higher prolactin levels were associated with a lower incidence of nosocomial infection (P = .006). Multivariable logistic regression showed that the Sequential Organ Failure Assessment score at intensive care unit admission (odds ratio, 1.24; 95% confidence interval, 1.04-1.48; P = .002) and the combined effect of prolactin levels with age (odds ratio, 1.018; 95% confidence interval, 1.01-1.031; P = .006) were associated with the development of delirium.",
            "output": [
                "Are high prolactin levels associated with more delirium in septic patients?"
            ]
        },
        {
            "id": "task847-bb42a7af87464958ba1c34b8d9d5b125",
            "input": "Brain white-matter lesions and cognitive impairment are increasing because of the increasing number of patients aged \u226580 y. Wall shear stress (WSS) plays a pivotal role as a fluid mechanical mediator in vascular reactivity and atherosclerosis. In this study, we investigated the associations among common carotid artery (CCA) WSS, white-matter lesions, and cognitive impairment in patients aged \u226580 y', 'We enrolled 384 patients aged \u226580 y. All subjects had CCA-WSS, brain white-matter hyperintensities (WMH), and Mini-Mental State Examination (MMSE) assessments and were divided into three groups using tertiles of mean and peak CCA-WSS.', 'For groups classified by the tertile of mean CCA-WSS, WMH, and WMH fraction were decreased; the MMSE score increased from low to high in the respective groups. Differences in WMH, WMH fraction, and the MMSE score were significant between any two groups (all adjusted p < 0.001). Groups classified by the tertile of peak CCA-WSS had the same pattern. Mean and peak CCA-WSS were significantly and inversely correlated with WMH (r = -0.575 and -0.570, respectively; p < 0.001) and WMH fraction (r = -0.574 and -0.569, respectively; p < 0.001) but positively correlated with the MMSE score (r = 0.390 and 0.278, respectively; p < 0.001). Multiple linear backward stepwise regression indicated the mean and peak CCA-WSS were significantly and independently associated with WMH, WMH fraction, and the MMSE score (all adjusted p < 0.001).",
            "output": [
                "Is low carotid artery wall shear stress independently associated with brain white-matter hyperintensities and cognitive impairment in older patients?"
            ]
        },
        {
            "id": "task847-674b425f9ab04a1b8f96572b5beddccc",
            "input": "Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive (\"primed\") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This \"primed\" phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling.', 'To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs).', 'Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations.', 'CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p\u22640.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (p<0.05) or 103 (p<0.01) are differentially active in asthma, with profiles that clearly characterize BSM cells of asthmatic individuals. Notably, we identified 7 clusters of coherently acting pathways functionally related to the disease, with ISPs down-regulated in asthma mostly targeting cell death-promoting pathways and up-regulated ones affecting cell growth and proliferation, inflammatory response, control of smooth muscle contraction and hypoxia-related signalization.",
            "output": [
                "Does large-scale profiling of signalling pathways reveal an asthma specific signature in bronchial smooth muscle cells?"
            ]
        },
        {
            "id": "task847-5ad06cca1b804ebd95ae0dcd670e273a",
            "input": "Checkpoint adaptation (entry into mitosis with damaged DNA) is a process that links arrest at the G2/M cell cycle checkpoint and cell death in cancer cells. It is not known, however, whether cells treated with the genotoxic agent, cisplatin, undergo checkpoint adaptation or if checkpoint adaptation is a major pathway leading to cell death or not. Therefore, we investigated the relationship between treatment with cisplatin and cytotoxicity in cancer cells.', 'Treatment of HT-29 human colorectal adenocarcinoma cells with cisplatin can induce cell death by one of two different mechanisms. Cells treated with a cytotoxic 30 \u03bcM amount of cisplatin died after undergoing checkpoint adaptation. Before dying, however, almost all treated cells were positive for histone \u03b3H2AX staining and contained high levels of cyclin B1. Rounded cells appeared that were positive for phospho-Ser10 histone H3, with low levels of phospho-Tyr15 cyclin-dependent kinase 1, high levels of cyclin-dependent kinase 1 activity, and checkpoint kinase 1 that was not phosphorylated on Ser345. These cells were in mitosis with damaged DNA. Strikingly, with 30 \u03bcM cisplatin, 81% of cells had entered mitosis before dying. By contrast, after treatment with 100 \u03bcM cisplatin, nearly all cells died but only 7% of cells had entered mitosis. Instead, these cells died by apoptosis; they were positive for annexin-V staining, contained cleaved caspase 3, cleaved caspase 9 and cleaved PARP and did not contain Mcl-1.",
            "output": [
                "Do cytotoxic amounts of cisplatin induce either checkpoint adaptation or apoptosis in a concentration-dependent manner in cancer cells?"
            ]
        },
        {
            "id": "task847-f0b8ad668bda44b792c86be5224b72ac",
            "input": "Andrographolide is the major bioactive compound isolated from Andrographis paniculata, a native South Asian herb used medicinally for its anti-inflammatory properties. In this study, we aimed to assess andrographolide's potential utility as an anti-neuroinflammatory therapeutic.\", 'The effects of andrographolide on lipopolysaccharide (LPS)-induced chemokine up-regulation both in mouse cortex and in cultured primary astrocytes were measured, including cytokine profiling, gene expression, and, in cultured astrocytes, activation of putative signaling regulators.', 'Orally administered andrographolide significantly attenuated mouse cortical chemokine levels from the C-C and C-X-C subfamilies. Similarly, andrographolide abrogated a range of LPS-induced chemokines as well as tumor necrosis factor (TNF)-\u03b1 in astrocytes. In astrocytes, the inhibitory actions of andrographolide on chemokine and TNF-\u03b1 up-regulation appeared to be mediated by nuclear factor-\u03baB (NF-\u03baB) or c-Jun N-terminal kinase (JNK) activation.",
            "output": [
                "Does andrographolide attenuate LPS-stimulated up-regulation of C-C and C-X-C motif chemokines in rodent cortex and primary astrocytes?"
            ]
        },
        {
            "id": "task847-2fa21ef50acd4cb7a24b0fd575ab8e68",
            "input": "Mesenchymal stromal cells (MSCs) have great potential for use in cell-based therapies for restoration of structure and function of many tissue types including smooth muscle.', 'We compared proliferation, immunophenotype, differentiation capability and gene expression of bone marrow-derived MSCs expanded in different media containing human serum, plasma and platelet lysate in combination with commonly used protocols for myogenic, osteogenic, chondrogenic and adipogenic differentiation. Moreover, we developed a xenogenic-free protocol for myogenic differentiation of MSCs.', 'Expansion of MSCs in media complemented with serum, serum + platelet lysate or plasma + platelet lysate were multipotent because they differentiated toward four mesenchymal (myogenic, osteogenic, chondrogenic, adipogenic) lineages. Addition of platelet lysate to expansion media increased the proliferation of MSCs and their expression of CD146. Incubation of MSCs in medium containing human serum or plasma plus 5% human platelet lysate in combination with smooth muscle cell (SMC)-inducing growth factors TGF\u03b21, PDGF and ascorbic acid induced high expression of ACTA2, TAGLN, CNN1 and/or MYH11 contractile SMC markers. Osteogenic, adipogenic and chondrogenic differentiations served as controls.",
            "output": [
                "Does choice of xenogenic-free expansion media significantly influence the myogenic differentiation potential of human bone marrow-derived mesenchymal stromal cells?"
            ]
        },
        {
            "id": "task847-e70b5f2c22264a609eef2c441a7a49a5",
            "input": "Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study.', 'MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity.', 'Both Gal-1-expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect.",
            "output": [
                "Is galectin-1 a local but not systemic immunomodulatory factor in mesenchymal stromal cells?"
            ]
        },
        {
            "id": "task847-cbd7342476b5438a845570746e933ca1",
            "input": "Inflammation within paraventricular nucleus of the hypothalamus (PVN), a key circulatory control center in the hypothalamus, is an important pathology of sympathetic hyperactivity. Brain inflammation is mainly mediated by microglia, innate immune cells in the brain. Activated microglia produce inflammatory cytokines with alteration of their morphology. Increase in inflammatory cytokines synthesis coincides with activation of microglia within PVN of angiotensin II-induced hypertensive model and myocardial infarction-induced heart failure model. Although the increase in inflammatory cytokines and the microglial activation within PVN were also seen in spontaneously hypertensive rats (SHR), the model of essential hypertension, their involvement in blood pressure regulation has still be fully clarified. In the present study, we examined whether activated microglia within PVN were involved in maintenance of established severe hypertension with sympathoexcitation.', 'Minocycline (25mg/kg/day), an inhibitor of microglial activation, or vehicle were orally administered to stroke-prone SHR (SHRSP) and normotensive Wistar-Kyoto (WKY) rats for 2 weeks from 15-weeks-old, the age of established hypertension.', 'Systolic blood pressure was comparable between minocycline treated-SHRSP and vehicle treated-SHRSP, whereas morphological analysis of microglia revealed smaller cell size in minocycline treated-SHRSP than vehicle treated-SHRSP, implying that minocycline deactivated microglia within PVN.",
            "output": [
                "Is activation of microglia within paraventricular nucleus of hypothalamus involved in maintenance of established hypertension?"
            ]
        },
        {
            "id": "task847-da60a39602f1412c991c41f7db1ec834",
            "input": "Large mega base-pair genomic regions show robust alterations in DNA methylation levels in multiple cancers. A vast majority of these regions are hypomethylated in cancers. These regions are generally enriched for CpG islands, Lamin Associated Domains and Large organized chromatin lysine modification domains, and are associated with stochastic variability in gene expression. Given the size and consistency of hypomethylated blocks (HMB) across cancer types, we hypothesized that the immediate causes of methylation instability are likely to be encoded in the genomic region near HMB boundaries, in terms of specific genomic or epigenomic signatures. However, a detailed characterization of the HMB boundaries has not been reported.', 'Here, we focused on ~13 k HMBs, encompassing approximately half of the genome, identified in colon cancer. We modeled the genomic features of HMB boundaries by Random Forest to identify their salient features, in terms of transcription factor (TF) binding motifs. Additionally we analyzed various epigenomic marks, and chromatin structural features of HMB boundaries relative to the non-HMB genomic regions.', 'We found that the classical promoter epigenomic mark--H3K4me3, is highly enriched at HMB boundaries, as are CTCF bound sites. HMB boundaries harbor distinct combinations of TF motifs. Our Random Forest model based on TF motifs can accurately distinguish boundaries not only from regions inside and outside HMBs, but surprisingly, from active promoters as well. Interestingly, the distinguishing TFs and their interacting proteins are involved in chromatin modification. Finally, HMB boundaries significantly coincide with the boundaries of Topologically Associating Domains of the chromatin.",
            "output": [
                "Do distinct genomic and epigenomic features demarcate hypomethylated blocks in colon cancer?"
            ]
        },
        {
            "id": "task847-e3d8f42e16444b8a82356560a304e615",
            "input": "Dual supraorbital and occipital nerve stimulation (SONS and ONS) have shown promising efficacy in treating primary headaches. However, its functional outcome is not well studied.', 'To present functional outcome studies of combined SONS and ONS for chronic migraine using verified metrics.', 'Consecutive patients with both SONS and ONS assessed with Migraine Disability Assessment (MIDAS) and Beck Depression Index (BDI) both preoperatively and postoperatively were studied. Selected predictor variables included patients with \u226550% improvement of pain, disability status, number of years from diagnosis to implantation, and narcotic use. Functional outcome variables included net improvement of ranked MIDAS and BDI scores. Multivariate analysis of variance was performed to assess the correlation between the outcome and predictor variables.', 'Sixteen patients (12 female; average age 52 years old) were studied. Follow-up ranged from 5 to 80 months (average 44.5; \u03c3\\u2009=\\u200921.4 months). At most recent follow-up, eight patients had a positive response (\u226550% improvement in headache), which was the only predictor of functional outcome (total MIDAS, MIDAS-B, and BDI) (p\\u2009=\\u20090.021). Of note, improvement in functional outcome was only significant during the perioperative 3-6 months period and not throughout long-term follow-up. Among the predictor variables, a strong inverse correlation was found between disability status and positive response to stimulation (r\\u2009=\\u2009-0.582).",
            "output": [
                "Does long-Term Pain Reduction Imply Improved Functional Outcome in Patients Treated With Combined Supraorbital and Occipital Nerve Stimulation for Chronic Migraine?"
            ]
        },
        {
            "id": "task847-cfe27eb150ae49d68d1e32049a9bfad1",
            "input": "Ischemic stroke is the leading cause of death and disability worldwide. To date, recombinant tissue plasminogen activator (rt-PA) remains the only safe and effective pharmaceutical treatment for brain ischemia, but delayed rt-PA administration leads to hyperperfusion, which severely limits its clinical efficacy.', 'In this study, we investigated the effect of epigallocatechin gallate (EGCG) in extending the therapeutic window of rt-PA using a rat middle cerebral artery occlusion (MCAO) model.', 'Simultaneous treatment of EGCG and rt-PA significantly recovered the neurobehavioral deficit, when administered even 4\\u2009hours after MCAO. Pathological examinations on the ischemic brain samples revealed that EGCG significantly alleviated the common side effects of delayed rt-PA treatment, including brain infarction, cerebral edema, and blood-brain barrier disruption. We further found that EGCG exerted its protective functions against delayed rt-PA through upregulation of plasminogen activator inhibitor-1, as well as downregulation of matrix metalloproteinases.",
            "output": [
                "Does epigallocatechin Gallate extend the Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment in Ischemic Rats?"
            ]
        },
        {
            "id": "task847-2626823258cc4393919a0e9723034131",
            "input": "To determine the effects of empagliflozin on adiposity indices among patients with type 2 diabetes mellitus.', 'Changes in weight, waist circumference, estimated total body fat, index of central obesity and visceral adiposity index were assessed using analysis of covariance and testing of treatment by strata for age, sex and baseline waist circumference in patients with type 2 diabetes mellitus randomized to blinded treatment with empagliflozin versus placebo in clinical trials of 12 weeks (cohort 1) or 24 weeks (cohort 2) duration.', 'This study comprised 3300 patients (cohort 1, N = 823; cohort 2, N = 2477). Empagliflozin reduced weight, waist circumference and adiposity indices versus placebo in both cohorts. Adjusted mean (95% confidence interval) change from baseline in empagliflozin versus placebo was -1.7 kg (-2.1 to -1.4 kg) and -1.9 kg (-2.1 to -1.7 kg) for body weight (p < 0.001); -1.3 cm (-1.8 to -0.7 cm) and -1.3 cm (-1.7 to -1.0 cm) for waist circumference (p < 0.001); -0.2% (-0.7% to 0.3%; p = 0.45) and -0.3% (-0.7% to 0.0%; p = 0.08) for estimated total body fat; -0.007 (-0.011 to -0.004) and -0.008 (-0.010 to -0.006) for index of central obesity (p < 0.001); and -0.3 (-0.5 to 0.0; p = 0.07) and -0.4 (-0.7 to -0.1; p = 0.003) for visceral adiposity index in cohorts 1 and 2, respectively. Adipose reductions were seen across most age, sex and waist circumference subgroups.",
            "output": [
                "Does empagliflozin reduce body weight and indices of adipose distribution in patients with type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-9787f76131a04ac8ae72707792521e32",
            "input": "Regulation of anabolic and catabolic factors is considered essential in maintaining the homoeostasis of healthy articular cartilage. In this study we investigated the influence of RNA binding proteins (RNABPs) in this process.', \"Using small interfering RNA (siRNA), RNABP expression was knocked down in SW1353 chondrosarcoma cells and human articular chondrocytes. Gene expression and messenger RNA (mRNA) decay of anabolic (SOX9, Aggrecan) and catabolic (matrix metalloproteinase (MMP)13) factors were analysed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). RNA-electromobility shift assays (EMSAs) were used to investigate RNABP interactions with the SOX9 mRNA 3' untranslated region (UTR). Immunohistochemical localisation of MMP13 and the RNABP human antigen R (HuR) was performed in E13.5 and E16.5 mouse embryo sections.\", \"SOX9 mRNA, mRNA half-life and protein expression were increased with siRNA targeting the RNABP tristetraprolin (TTP) in both HACs and SW1353s. TTP knockdown also stimulated aggrecan mRNA expression but did not affect its stability. RNA-EMSAs demonstrated that adenine uracil (AU)-rich elements in the SOX9 mRNA 3'UTR interacted with chondrocyte proteins with three specific elements interacting with TTP. HuR knockdown significantly increased MMP13 expression and also regulated the expression of a number of known transcriptional repressors of MMP13. HuR was ubiquitously expressed within mouse embryos yet displayed regional down-regulation within developing skeletal structures.",
            "output": [
                "Do rNA binding proteins regulate anabolic and catabolic gene expression in chondrocytes?"
            ]
        },
        {
            "id": "task847-2a9d60d39f324c3ba932fe87d0192dff",
            "input": "The purpose was to investigate whether patient-specific factors (PSF) and surgically modifiable factors (SMF), measured by means of a computer-assisted navigation system, can predict the Knee Society Scores (KSS) after total knee arthroplasty (TKA).', 'Data from 99 patients collected during a randomized clinical trial were used for this secondary data analysis. The KSS scores of the patients were measured preoperatively and at 4-years follow-up. Multiple regression analyses were performed to investigate which combination of variables would be the best to predict the 4-years KSS scores.', 'When considering SMF alone the combination of four of them significantly predicted the 4-years KSS-F score (p\\u2009=\\u20090.009), explaining 18\\xa0% of its variation. When considering only PSF the combination of age and body weight significantly predicted the 4-years KSS-F (p\\u2009=\\u20090.008), explaining 11\\xa0% of its variation. When considering both groups of predictors simultaneously the combination of three PSF and two SMF significantly predicted the 4-years KSS-F (p\\u2009=\\u20090.007), explaining 20\\xa0% of its variation.",
            "output": [
                "Do surgically modifiable factors measured by computer-navigation together with patient-specific factors predict knee society score after total knee arthroplasty?"
            ]
        },
        {
            "id": "task847-8d700fc2ff1f425caf53cca14cddccd2",
            "input": "Fetal exposure to maternal prenatal stress hormones such as cortisol exerts influences on the developing nervous system that persist and include risk for internalizing symptoms later in life. Placental corticotropin-releasing hormone (pCRH) is a feto-placental stress signal that also shapes fetal neurodevelopment and may be a more direct indicator of the fetal experience than maternal stress hormones. The programming effects of pCRH on child development are unknown. The current investigation examined associations between prenatal maternal and placental stress hormone exposures (maternal cortisol and pCRH) and child self-reported internalizing symptoms at age 5.', \"Maternal plasma cortisol and pCRH levels were measured at 15, 19, 25, 31, and 36 weeks' gestation in a sample of 83 women and their 91 children (8 sibling pairs from separate pregnancies), who were born full-term. Child self-reported internalizing symptoms at age 5 were obtained using scales of the Berkeley Puppet Interview.\", 'Placental CRH profiles (including elevations in mid-gestation) were associated with higher levels of internalizing symptoms at age 5. This effect was not explained by critical prenatal or postnatal influences, including obstetric risk, concurrent maternal psychological state, and family socio-economic status. Prenatal maternal cortisol was not significantly associated with child self-reported internalizing symptoms.",
            "output": [
                "Is fetal exposure to placental corticotropin-releasing hormone associated with child self-reported internalizing symptoms?"
            ]
        },
        {
            "id": "task847-2ca6155af18f4e1db2f2e6c25bc1d2d7",
            "input": "In 2010, the American Heart Association developed a new definition of ideal cardiovascular health (CVH) based on seven cardiovascular health metrics. This study aimed to investigate the relationship between modified ideal CVH metrics and the risk of stroke in the rural population of Northeast China.', 'We included 11,417 adults from the rural population in Northeast China and collected all the information, including the baseline characteristics, history of stroke, and the seven ideal CVH metrics.', 'Our results showed that the presence of stroke was associated with high body mass index (BMI), poor diet score (salt intake), high total cholesterol (TC), high blood pressure (BP), and high fasting plasma glucose (FPG). The prevalence of stroke increased as the number of ideal CVH metrics decreased, and peaked to 13.1% among those with only one ideal CVH metric. Participants with only one ideal CVH had a 4.40-fold increased susceptibility of stroke than those with all seven ideal health metrics.",
            "output": [
                "Is modified Ideal Cardiovascular Health Status Associated with Lower Prevalence of Stroke in Rural Northeast China?"
            ]
        },
        {
            "id": "task847-5fb989c6864843afb2ca477ffec89327",
            "input": "Olfaction is a fundamental sense through which most animals perceive the external world. The olfactory system detects odors via specialized sensory organs such as the main olfactory epithelium and the vomeronasal organ. Sensory neurons in these organs use G-protein coupled receptors to detect chemosensory stimuli. The odorant receptor (OR) family is expressed in sensory neurons of the main olfactory epithelium, while the adult vomeronasal organ is thought to express other types of receptors.', 'Here, we describe Olfr692, a member of the OR gene family identified by next-generation RNA sequencing, which is highly upregulated and non-canonically expressed in the vomeronasal organ. We show that neurons expressing this gene are activated by odors emanating from pups. Surprisingly, activity in Olfr692-positive cells is sexually dimorphic, being very low in females. Our results also show that juvenile odors activate a large number of Olfr692 vomeronasal neurons in virgin males, which is correlated with the display of infanticide behavior. . In contrast, activity substantially decreases in parenting males (fathers), where infanticidal aggressive behavior is not frequently observed.",
            "output": [
                "Is detection of pup odors by non-canonical adult vomeronasal neurons expressing an odorant receptor gene influenced by sex and parenting status?"
            ]
        },
        {
            "id": "task847-5088e4602b8c48479575f15d2615cc76",
            "input": "Cognitive impairment is a common feature of late-life bipolar disorder (BD). Yet, there is limited information on the biological mechanisms associated with this process. It is uncertain whether cognitively impaired patients with BD may present the Alzheimer's disease (AD) bio-signature in the cerebrospinal fluid (CSF), defined as a combination of low concentrations of the amyloid-beta peptide (A\u03b21-42 ) and high concentrations of total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau). In this study, we sought to determine whether cognitive impairment in elderly patients with BD is associated with the AD CSF bio-signature.\", 'Seventy-two participants were enrolled in the study. The test group comprised older adults with BD and mild cognitive impairment (BD-MCI; n\\xa0=\\xa016) and the comparison groups comprised patients with dementia due to AD (n\\xa0=\\xa017), patients with amnestic MCI (aMCI; n\\xa0=\\xa014), and cognitively healthy older adults (control group; n\\xa0=\\xa025). CSF samples were obtained by lumbar puncture and concentrations of A\u03b21-42 , T-tau and P-tau were determined.', 'CSF concentrations of all biomarkers were significantly different in the AD group compared to all other groups, but did not differentiate BD-MCI subjects from aMCI subjects and controls. BD-MCI patients had a non-significant reduction in CSF A\u03b21-42 compared to controls, but this was still higher than in the AD group. Concentrations of T-tau and P-tau in BD-MCI patients were similar to those in controls, and significantly lower than those in AD.",
            "output": [
                "Is cognitive impairment in late-life bipolar disorder associated with Alzheimer 's disease pathological signature in the cerebrospinal fluid?"
            ]
        },
        {
            "id": "task847-72010d8822244ba38e08eb82d4e628d5",
            "input": "Parent feeding practices affect risk of obesity in children. Latino children are at higher risk of obesity than the general population, yet valid measure of feeding practices, one of which is the Infant Feeding Styles Questionnaire (IFSQ), have not been formally validated in Spanish.', 'To validate the IFSQ among Latino families, we conducted confirmatory factor analysis of pressuring, restrictive, and responsive feeding constructs from the IFSQ.', \"The IFSQ was administered at the 12-month visit in the Greenlight study, a multi-center cluster randomized trial to prevent obesity. Parents were included if they were of Latino origin (n\\xa0=\\xa0303) and completed an English or Spanish language modified IFSQ (without the indulgence construct). Scores from nine sub-constructs of the IFSQ were compared between English and Spanish language versions. We tested reliability with Cronbach's alpha coefficients and performed confirmatory factor analysis to examine factor loadings and goodness of fit characteristics, modifying constructs to achieve best fit.\", 'Of 303 parents completing the IFSQ, 84% were born outside the US, and 74% completed the IFSQ in Spanish. Reliability coefficients ranged from 0.28 to 0.61 for the laissez-faire sub-constructs and from 0.58 to 0.83 for the pressuring, restrictive, and responsive sub-constructs. Results for all coefficients were similar between participants responding to an English and Spanish version of the IFSQ. Goodness of fit indices ranged from CFI 0.82-1 and RMSEA 0.00-0.31, and the model performed best in pressuring-soothing (CFI 1.0, RMSEA 0.00) and restrictive-amount (CFI 0.98, RMSEA 0.1) sub-constructs.",
            "output": [
                "Does confirmatory factor analysis of the Infant Feeding style Questionnaire in Latino families?"
            ]
        },
        {
            "id": "task847-3b63075ff996461a82c2e7a757590078",
            "input": "Since manganese (Mn) is capable of stimulating the hypothalamic-pituitary unit and advancing female puberty, we assessed the possibility that this element might overcome some of the detrimental effects of prepubertal alcohol (ALC) exposure on the hypothalamic control of pituitary function.', 'Rats received either saline or Mn (10mg/kg) daily by gastric gavage from day 12 to day 31. After weaning, all rats were provided Lab Chow diet ad libitum until day 27 when they began receiving either the Bio Serv control or ALC diet regime. On day 31, the medial basal hypothalamus (MBH) was collected to assess luteinizing hormone-releasing hormone (LHRH) and cyclooxygenase 2 (COX2) protein levels. Release of prostaglandin-E2 (PGE2), LHRH and serum luteinizing hormone (LH) were also assessed. Other animals were not terminated on day 31, but remained in study to assess timing of puberty.', 'Short-term ALC exposure caused elevated hypothalamic LHRH content, suggesting an inhibition in peptide release, resulting in a decrease in LH. Both actions of ALC were reversed by Mn supplementation. COX2 synthesis, as well as PGE2 and LHRH release were suppressed by ALC exposure, but Mn supplementation caused an increase in COX2 synthesis and subsequent PGE2 and LHRH release in the presence of ALC. Mn supplementation also ameliorated the action of ALC to delay puberty.",
            "output": [
                "Does manganese protect against the effects of alcohol on hypothalamic puberty-related hormones?"
            ]
        },
        {
            "id": "task847-063d20788f0d4a55a64ab374a82b3301",
            "input": "Many prognostic biomarkers associated with androgen signaling have been proposed in PC. The role of tripartite motif (TRIM) proteins remains unclear in PC. We investigated TRIM protein 47 (TRIM47) expression levels in human prostate tissues.', 'We performed immunohistochemistry using original TRIM47 antibody in prostate tissues obtained by radical prostatectomy (n\\xa0= 105). Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity (IR) scores (range, 0-8) were calculated as the sum of the proportion and intensity scores. TRIM47 expression levels were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Associations between the clinicopathologic features of the patients and their TRIM47 status were analyzed.', 'Western blot analysis validated the specificity of the anti-TRIM47 antibody in 293T cells. TRIM47 expression levels were found to be significantly increased in PC compared to benign tissues by both immunohistochemistry (P\\xa0< .0001) and qRT-PCR (P\\xa0= .003). Additionally, advanced pathologic stage (\u2265 T3b) was found to be associated with high TRIM47 IR scores (\u2265 4; P\\xa0= .04). Furthermore, high TRIM47 IR scores were also significantly correlated with worse cancer-specific survival rates in multivariate regression analyses (hazard ratio, 6.82; P\\xa0= .016).",
            "output": [
                "Does increased Expression of Tripartite Motif ( TRIM ) 47 be a Negative Prognostic Predictor in Human Prostate Cancer?"
            ]
        },
        {
            "id": "task847-3fc0cdc6323e4de6834f3f603c20ad87",
            "input": "Preeclampsia is known to be associated with reduced circulating levels of estrogen. The effects of estrogen in preeclampsia are normally mediated by the classical estrogen receptors. Intriguingly, a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), has been recently found to play an important role in several estrogenic effects. However, the mechanisms by which GPR30 may mediate the development of preeclampsia remain unknown.', 'We observed that the expression of GPR30 in placental trophoblast cells is lower in preeclamptic placentas compared with normotensive controls. We then investigated the role of GPR30 in trophoblast cell invasion by utilizing placental explants and the immortalized human trophoblast cell line (HTR8/SVneo).', 'The selective GPR30 agonist G1 and a general estrogen receptors agonist 17-\u03b2-estradiol (E2) both improved trophoblast cells invasion by upregulating MMP9 expression and the PI3K-Akt signaling pathway. This effect was abolished by a selective GPR30 inhibitor G15, implying that GPR30 may be involved in regulating trophoblast invasion, and that down-regulation of this receptor may result in the development of preeclampsia.",
            "output": [
                "Does g protein-coupled receptor 30 regulate trophoblast invasion and its deficiency is associated with preeclampsia?"
            ]
        },
        {
            "id": "task847-8f53058fbae5411f9e47319aa99bfe82",
            "input": "Claudin-5, claudin-9, and claudin-11 are expressed in endothelial cells to constitute tight junctions, and their deficiency may lead to hyperpermeability, which is the initiating process and pathological basis of cardiovascular disease. Although tongxinluo (TXL) has satisfactory antianginal effects, whether and how it modulates claudin-5, claudin-9, and claudin-11 in hypoxia-stimulated human cardiac microvascular endothelial cells (HCMECs) have not been reported.', 'In this study, HCMECs were stimulated with CoCl2to mimic hypoxia and treated with TXL. First, the messenger RNA (mRNA) expression of claudin-5, claudin-9, and claudin-11 was confirmed. Then, the protein content and distribution of claudin-9, as well as cell morphological changes were evaluated after TXL treatment. Furthermore, the distribution and content histone H3K9 acetylation (H3K9ac) in the claudin-9 gene promoter, which guarantees transcriptional activation, were examined to explore the underlying mechanism, by which TXL up-regulates claudin-9 in hypoxia-stimulated HCMECs.', 'We found that hypoxia-suppressed claudin-9 gene expression in HCMECs (F = 7.244; P = 0.011) and the hypoxia-suppressed claudin-9 could be reversed by TXL (F = 61.911; P = 0.000), which was verified by its protein content changes (F = 29.142; P = 0.000). Moreover, high-dose TXL promoted the cytomembrane localization of claudin-9 in hypoxia-stimulated HCMECs, with attenuation of cell injury. Furthermore, high-dose TXL elevated the hypoxia-inhibited H3K9ac in the claudin-9 gene promoter (F = 37.766; P = 0.000), activating claudin-9 transcription.",
            "output": [
                "Does tongxinluo reverse the Hypoxia-suppressed Claudin-9 in Cardiac Microvascular Endothelial Cells?"
            ]
        },
        {
            "id": "task847-4a60be91ea254577874c60893266b354",
            "input": "Doxorubicin (Dox) is a potent anticancer agent that is widely used in the treatment of a variety of cancers, but its usage is limited by cumulative dose-dependent cardiotoxicity mainly due to oxidative damage. Ataxia telangiectasia mutated (ATM) kinase is thought to play a role in mediating the actions of oxidative stress. Here, we show that ATM in cardiac fibroblasts is essential for Dox-induced cardiotoxicity.', 'ATM knockout mice showed attenuated Dox-induced cardiotoxic effects (e.g. cardiac dysfunction, apoptosis, and mortality). As ATM was expressed and activated predominantly in cardiac fibroblasts, fibroblast-specific Atm-deleted mice (Atm(fl/fl);Postn-Cre) were generated to address cell type-specific effects, which showed that the fibroblast is the key lineage mediating Dox-induced cardiotoxicity through ATM. Mechanistically, ATM activated the Fas ligand, which subsequently regulated apoptosis in cardiomyocytes at later stages. Therapeutically, a potent and selective inhibitor of ATM, KU55933, when administered systemically was able to prevent Dox-induced cardiotoxicity.",
            "output": [
                "Does ataxia telangiectasia mutated in cardiac fibroblasts regulate doxorubicin-induced cardiotoxicity?"
            ]
        },
        {
            "id": "task847-f9b1c67f40364d3e858703f9fad9fb32",
            "input": "The present study evaluated whether the poorer baseline performance of cochlear implant (CI) users or the technical and/or physiological properties of CI stimulation are responsible for the absence of masking release.', 'This study measured speech reception thresholds (SRTs) in continuous and modulated noise as a function of signal to noise ratio (SNR).', 'A total of 24 subjects participated: 12 normal-hearing (NH) listeners and 12 subjects provided with recent MED-EL CI systems.', 'The mean SRT of CI users in continuous noise was -3.0 \u00b1 1.5 dB SNR (mean \u00b1 SEM), while the normal-hearing group reached\\u2009-5.9 \u00b1 0.8 dB SNR. In modulated noise, the difference across groups increased considerably. For CI users, the mean SRT worsened to -1.4 \u00b1 2.3 dB SNR, while it improved for normal-hearing listeners to -18.9 \u00b1 3.8 dB SNR.",
            "output": [
                "Do the effect of fluctuating maskers on speech understanding of high-performing cochlear implant users?"
            ]
        },
        {
            "id": "task847-6b75cca0453b48e885668d54c3a17c8f",
            "input": "Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognised indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischemic stroke, and investigated the clinical characteristics of ischemic stroke patients with and those without kidney dysfunction.', 'The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (<60\\u2009mL/min/1.73\\u2009m', 'Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR >31.2\\u2009mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P\\u2009=\\u20090.0005) was independently associated with a poor outcome, while a low eGFR was not associated.",
            "output": [
                "Does high urinary albumin/creatinine ratio at admission predict poor functional outcome in patients with acute ischemic stroke?"
            ]
        },
        {
            "id": "task847-346b3d987cd1463b95cc50925af3d702",
            "input": "The rapid industrialisation and urbanisation fuelled by a fast-growing population has led to the generation of a huge amount of waste in most communities in developing countries. The hidden disorders and health dangers in waste dumps are often ignored. The waste generated in local communities is usually of a mixed type consisting of domestic waste and waste from small-scale industrial activities. Among these wastes are toxic metals, lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), halogenated organic compounds, plastics, remnants of paints that are themselves mixtures of hazardous substances, hydrocarbons and petroleum product-contaminated devices. Therefore, there is the urgent need to create an awareness of the harmful health effect of toxic wastes in developing countries, especially Nigeria.', 'This is a review aimed at creating awareness on the hidden dangers of waste dumps to health in local communities in developing countries. Many publications in standard outlets use the following keywords: cancer, chemical toxicity, modern environmental health hazards, waste management and waste speciation in PubMed, ISI, Toxbase environmental digest, related base journals, and some standard textbooks, as well as the observation of the researcher between 1959 and 2014.', 'Studies revealed the preponderance of toxic chemicals such as Pb, Cd, As and Hg in dump sites that have the risk of entering food chain and groundwater supplies, and these can give rise to endemic malnutrition and may also increase susceptibility to mutagenic substances, thereby increasing the incidence of cancer in developing countries.",
            "output": [
                "Does waste dump in local communities in developing countries and hidden danger to health?"
            ]
        },
        {
            "id": "task847-11331c73d8fb45849c158b5fc4699534",
            "input": "Many patients with psoriasis have developed acute promyelocytic leukemia (APL) whereas few reports on psoriasis-associated APL were found in the published literature. This study was aimed to study the etiology, clinical characteristics, and prognosis of psoriasis-associated APL and to map a suitable treatment regime for this condition.', 'This study retrospectively analyzed the clinical data of 17 patients with psoriasis-associated APL diagnosed and treated in our hospital in the past decade.', 'The 17 patients accounted for 8.3% of the total patients diagnosed with de novo APL during the same period in our hospital. Their clinical characteristics of APL were similar to those of general APL. Four patients had a definite history of taking bimolane. All patients received arsenic trioxide (ATO)-based remission induction and postremission treatment. After induction, 15 patients (88%) achieved hematologic complete remission. With a median follow-up of 27 months, the 3-year estimates of overall survival were 77.2%\\u2009\u00b1\\u200912.4% and the 3-year estimates of event-free survival were 70.6%\\u2009\u00b1\\u200913.5%. In addition, the ATO-based remission induction and postremission treatment significantly improved psoriasis symptoms in 83 and 85.7% of patients, respectively. Through the final follow-up, no chronic arsenicosis or secondary malignancy was observed.",
            "output": [
                "Is arsenic trioxide-based therapy suitable for patients with psoriasis-associated acute promyelocytic leukemia - A retrospective clinical study?"
            ]
        },
        {
            "id": "task847-b31d0f8a33a54a4b85e124429d7c7fa7",
            "input": "Novel taste memories, critical for animal survival, are consolidated to form long term memories which are dependent on translation regulation in the gustatory cortex (GC) hours following acquisition. However, the role of transcription regulation in the process is unknown.', 'Here, we report that transcription in the GC is necessary for taste learning in rats, and that drinking and its consequences, as well as the novel taste experience, affect transcription in the GC during taste memory consolidation. We show differential effects of learning on temporal dynamics in set of genes in the GC, including Arc/Arg3.1, known to regulate the homeostasis of excitatory synapses.",
            "output": [
                "Does fluid consumption and taste novelty determine transcription temporal dynamics in the gustatory cortex?"
            ]
        },
        {
            "id": "task847-07a74b7ee55c436eb966a9be93dbed7a",
            "input": "Minimal residual disease (MRD) is defined as the presence of sub-microscopic levels of leukaemia. Measurement of MRD from bone marrow at the end of induction chemotherapy (day 28) for childhood acute lymphoblastic leukaemia (ALL) can highlight a large group of patients (>40%) with an excellent (>90%) short-term event-free survival (EFS). However, follow-up in recent published trials is relatively short, raising concerns about using this result to infer the safety of further therapy reduction in the future.', 'We examined MRD data on 225 patients treated on one of three UKALL trials between 1997 and 2003 to assess the long-term (>10\\u2005years follow-up) outcome of those patients who had low-risk MRD (<0.01%) at day 28.', 'Our pilot data define a cohort of 53% of children with MRD <0.01% at day 28 who have an EFS of 91% and long-term overall survival of 97%. Of 120 patients with day-28 MRD <0.01% and extended follow-up, there was one death due to treatment-related toxicity, one infectious death while in complete remission, and four relapse deaths.",
            "output": [
                "Is excellent outcome of minimal residual disease-defined low-risk patients sustained with more than 10 years follow-up : results of UK paediatric acute lymphoblastic leukaemia trials 1997-2003?"
            ]
        },
        {
            "id": "task847-f39e2eb80f344b7e817aa548c516bd94",
            "input": "Previous studies have found that insulin or insulin-like growth factor treatment can stimulate fracture healing in diabetic and normal animal models, and increase fusion rates in a rat spinal fusion model. Insulin-mimetic agents, such as zinc, have demonstrated antidiabetic effects in animal and human studies, and these agents that mimic the effects of insulin could produce the same beneficial effects on bone regeneration and spinal fusion.', 'The purpose of this study was to analyze the effects of locally applied zinc on spinal fusion in a rat model.', 'Institutional Animal Care and Use Committee-approved animal study using Sprague-Dawley rats was used as the study design.', 'Thirty Sprague-Dawley rats (450-500\\u2009g) underwent L4-L5 posterolateral lumbar fusion (PLF). After decortication and application of approximately 0.3\\u2009g of autograft per side, one of three pellets were added to each site: high-dose zinc calcium sulfate (ZnCaSO4), low-dose ZnCaSO4 (half of the high dose), or a control palmitic acid pellet (no Zn dose). Systemic blood glucose levels were measured 24 hours postoperatively. Rats were sacrificed after 8weeks and the PLFs analyzed qualitatively by manual palpation and radiograph review, and quantitatively by micro-computed tomography (CT) analysis of bone volume and trabecular thickness. Statistical analyses with p-values set at .05 were accomplished with analysis of variance, followed by posthoc tests for quantitative data, or Mann-Whitney rank tests for qualitative assessments.', 'Compared with controls, the low-dose zinc group demonstrated a significantly higher manual palpation grade (p=.011), radiographic score (p=.045), and bone formation on micro-CT (172.9\\u2009mm(3) vs. 126.7\\u2009mm(3) for controls) (p<.01). The high-dose zinc also demonstrated a significantly higher radiographic score (p=.017) and bone formation on micro-CT (172.7\\u2009mm(3) vs. 126.7\\u2009mm(3)) (p<.01) versus controls, and was trending toward higher manual palpation scores (p=.058).",
            "output": [
                "Does zinc have insulin-mimetic properties which enhance spinal fusion in a rat model?"
            ]
        },
        {
            "id": "task847-c5cd89d25f104dbaa8ca3e9cb962314f",
            "input": "Alcohol increases the tendency for risky driving in some individuals but not others. Little is known about the factors underlying this individual difference. Studies find that those who underestimate their blood alcohol concentration (BAC) following a dose of alcohol tend to be more impulsive and report greater willingness to drive after drinking than those who estimate their BACs to be greater than their actual BAC. BAC underestimation could contribute to risky driving behavior following alcohol as such drivers might perceive little impairment in their driving ability and thus no need for caution.', \"This study was designed to test the relationship between drivers' BAC estimations following a dose of alcohol or a placebo and the degree of risky driving they displayed during a simulated driving test.\", 'Forty adult drivers performed a simulated driving test and estimated their blood alcohol concentration after receiving a dose of alcohol (0.65 g/kg for men and 0.56 g/kg for women) or a placebo.', 'Alcohol increased risk-taking and impaired driving skill. Those who estimated their BAC to be lower were the riskiest drivers following both alcohol and placebo.",
            "output": [
                "Do drivers who self-estimate lower blood alcohol concentrations are riskier drivers after drinking?"
            ]
        },
        {
            "id": "task847-3efa3dda6cd84a24bc9eed73f45db4fa",
            "input": "To evaluate the accuracy of the CEREC CAD/CAM system in reproducing the maximum intercuspal contacts of the casts, which include posterior teeth preparation for a fixed partial denture (FPD).', 'Ten pairs of gypsum casts were mounted in articulators in maximum intercuspal position (MIP) to serve as patient simulation models. Tooth #19 was removed from the cast. Occlusal contacts in MIP were identified with articulating paper, and digital impressions of the casts with unprepared teeth and buccal images in MIP were taken. Teeth #18 and #20 were prepared for an FPD, and full- and half-arch digital impressions of the casts with prepared teeth and buccal images from different sides were taken. In each situation, screenshot images of the virtual casts with occlusal contacts were saved as JPEG files. The proportions of congruence of virtual contacts with cast contacts were analyzed by superimposing screenshot images of the virtual casts onto the screenshot images of the casts with the indicated occlusal contacts in a transparent manner using an image-processing program. The data were statistically analyzed with a paired t-test.', 'The highest percentages of virtually indicated contacts identical to the cast contacts were observed in non-prepared full-arch digital impressions. Comparison of full-arch impressions taken before and after tooth preparation showed no difference for congruence even if the buccal image was taken from the contralateral or ipsilateral side (p > 0.05). After tooth preparation, comparing full- and half-arch digital impressions revealed that half-arch impression showed significantly lower percentages of identical contacts (p < 0.05). When comparing the buccal image side, no significant difference was detected between ipsilateral and contralateral images both for non-prepared and prepared casts (p > 0.05).",
            "output": [
                "Does comparison of Maximum Intercuspal Contacts of Articulated Casts and Virtual cast Requiring Posterior Fixed Partial Dentures?"
            ]
        },
        {
            "id": "task847-41a46c31ed5240278c44a198d66607b0",
            "input": "Ehlers Danlos Syndrome is a rare form of inherited connective tissue disorder, which primarily affects skin, joints, muscle, and blood cells. The current study aimed at finding the mutation that causing EDS type VII C also known as \"Dermatosparaxis\" in this family.', 'Through systematic data querying of the electronic medical records (EMRs) of over 80,000 individuals, we recently identified an EDS family that indicate an autosomal dominant inheritance. The family was consented for genomic analysis of their de-identified data. After a negative screen for known mutations, we performed whole genome sequencing on the male proband, his affected father, and unaffected mother. We filtered the list of non-synonymous variants that are common between the affected individuals.', 'The analysis of non-synonymous variants lead to identifying a novel mutation in the ADAMTSL2 (p. Gly421Ser) gene in the affected individuals. Sanger sequencing confirmed the mutation.",
            "output": [
                "Does systematic data-querying of large pediatric biorepository identify novel Ehlers-Danlos Syndrome variant?"
            ]
        },
        {
            "id": "task847-6b4b9cb780774c4cb7c58e2f1bafeb7b",
            "input": "Aberrant signal transducer and activator of transcription 3 (STAT-3) molecular signaling elicit hepatocellular carcinoma (HCC) in humans. Therefore, targeting STAT-3 is considered as an attractive option towards suppression of HCC in humans.', 'Our objective is to identify a potential small molecule inhibitor that can specifically target STAT-3 and suppress HCC.', 'In this study, we analyze a group of sesquiterpene lactone (STL) candidates that has been recently reported in preclinical trials against cancer by a unified computational and experimental approach.', 'Our virtual analysis of the STL candidates revealed Artesunate (ATS) as the best potential inhibitor of STAT-3 with comparable potency to specific inhibitor S3I-201. We also observed that ATS inhibited IL-6 driven STAT-3-DNA binding activity with comparable potency to S3I-201 in a cell free system. Furthermore ATS was observed to interfere with STAT-3 dimerization and suppression of both constitutive and IL-6 inducible STAT-3 in vitro. Nevertheless, we also observed that ATS modulated STAT-3 dependent targets (procaspase-3, Bcl-xl and survivin) favoring occurrence of apoptosis in vitro. Overall, the putative inhibition of STAT-3 by ATS suggested its capacity to interfere with STAT-3 dimerization by binding to the SH2 domain of STAT-3 monomer. It resulted in suppression of STAT-3 and also favored promotion of in vitro cells towards apoptosis. Consequently, ATS also exhibited selective cytotoxicity of cancer cells over normal cells in vitro.",
            "output": [
                "Does artesunate as an Anti-Cancer Agent Targets Stat-3 and Favorably suppress Hepatocellular Carcinoma?"
            ]
        },
        {
            "id": "task847-fe1ea80b691c4f0eb987aad25d16a909",
            "input": "Bone infections after trauma, i.e. posttraumatic osteomyelitis, pose one of the biggest problems of orthopedic surgery. Even after sufficient clinical therapy including vast debridement of infected bone and antibiotic treatment, regeneration of postinfectious bone seems to be restricted. One explanation includes the large sized defects resulting from sufficient debridement. Furthermore, it remains unclear if inflammatory processes after bone infection do affect bone regeneration. For continuing studies in this field, an animal model is needed where bone regeneration after sufficient treatment can be studied in detail.', 'For this purpose we created a stable infection in murine tibiae by Staphylococcus aureus inoculation. Thereafter, osteomyelitic bones were debrided thoroughly and animals were subsequently treated with antibiotics. Controls included debrided, non-infected, as well as infected animals exclusively treated with antibiotics. To verify sufficient treatment of infected bone, different assessments detecting S. aureus were utilized: agar plates, histology and RT-qPCR.', 'All three detection methods revealed massive reduction or eradication of S. aureus within debrided bones 1 and 2 weeks postoperatively, whereas sole antibiotic therapy could not provide sufficient treatment of osteomyelitic bones. Debrided, previously infected bones showed significantly decreased bone formation, compared to debrided, non-infected controls.",
            "output": [
                "Does surgical Debridement be Superior to Sole Antibiotic Therapy in a Novel Murine Posttraumatic Osteomyelitis Model?"
            ]
        },
        {
            "id": "task847-ce65f24b77ff494bad4c1c4f36d3033f",
            "input": "Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages.', 'Macrophage-specific GCI-58 transgenic mice (TG) and wild type mice (WT) were fed a high fat diet (HFD), and RAW264.7 cells were treated with lipopolysaccharide (LPS). The peroxisome proliferator-activated receptor (PPAR) signaling was detected. The inflammatory responsiveness and mitochondrial function were examined.', 'TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPAR\u03b3 expression and activity, respectively. Most importantly, the PPAR\u03b3-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPAR\u03b3 in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC) to the PPAR\u03b3 promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPAR\u03b3 signaling in macrophages.",
            "output": [
                "Does macrophage CGI-58 attenuate Inflammatory Responsiveness via Promotion of PPAR\u03b3 Signaling?"
            ]
        },
        {
            "id": "task847-2d9275f4c2a144fbaa008c635b5ff6fd",
            "input": "The objective of this study was to evaluate the effects of abacavir on intracellular ribavirin triphosphate and plasma ribavirin trough concentrations.', 'Hepatitis C virus-infected subjects who had been cured or failed prior treatment were randomized to 8 weeks of ribavirin alone (N\\u200a=\\u200a14; weight-based dosing) or weight-based ribavirin\\u200a+\\u200aabacavir (N\\u200a=\\u200a14; 300 mg orally every 12 h). Ribavirin trough concentrations were measured on days 14, 28, 42 and 56; PBMCs for ribavirin triphosphate determination were sampled on days 28 and 56, pre-dose and at 6 and 12 h post-dose. ClinicalTrials.gov: NCT01052701.', 'Twenty-six subjects completed the study (24 males, 17 Caucasians, median age 52 years); 2 were excluded for missed pharmacokinetic visits. Fourteen subjects received ribavirin\\u200a+\\u200aabacavir and 12 received ribavirin alone. Mean\\u200a\u00b1\\u200aSD plasma ribavirin trough concentrations (\u03bcg/mL) on days 14, 28, 42 and 56, respectively, were not significantly different with coadministration of abacavir (1.54\\u200a\u00b1\\u200a0.60, 1.93\\u200a\u00b1\\u200a0.54, 2.14\\u200a\u00b1\\u200a0.73 and 2.54\\u200a\u00b1\\u200a1.05) compared with ribavirin alone (1.48\\u200a\u00b1\\u200a0.32, 2.08\\u200a\u00b1\\u200a0.41, 2.32\\u200a\u00b1\\u200a0.47 and 2.60\\u200a\u00b1\\u200a0.62) (P\\u200a>\\u200a0.40). Mean ribavirin triphosphate intracellular concentrations (pmol/10(6) cells) on days 28 and 56, respectively, did not differ statistically between abacavir users (11.98\\u200a\u00b1\\u200a9.86 and 15.87\\u200a\u00b1\\u200a12.52) and non-users (15.91\\u200a\u00b1\\u200a15.58 and 15.93\\u200a\u00b1\\u200a12.69) (P\\u200a>\\u200a0.4). Adverse events were mild or moderate, except for three grade 3 occurrences of transaminitis, cholecystitis and low absolute neutrophil count that resolved and were judged not attributable to study medications.",
            "output": [
                "Are plasma and intracellular ribavirin concentrations significantly altered by abacavir in hepatitis C virus-infected patients?"
            ]
        },
        {
            "id": "task847-3fc32122090e4330b918929ad3e4858b",
            "input": "Current approaches for the treatment of gingival exposure are often time- and cost-consuming and/or rather invasive. We previously observed a strong correlation between the presence of gingival excess and midfacial depression and here propose an easy 1-step correction technique as a new strategy to improve gingival exposure.', 'From February 2004 to December 2012, 42 patients with gingival exposure associated with different degrees of midfacial depression, defined by Frankfort horizontal plane-labrale superius-subspinale angle and sella-nasion-A point angle, were treated by implantation of an inverted m-shaped expanded polytetrafluoroethylene at the base of the piriform aperture in a subperiosteal location. Patient pictures were taken preoperatively and postoperatively to assess gingival exposure at rest and fullest smile, as well as measurements of upper lip length, nasolabial angle, and facial convexity angle. A postoperative patient satisfaction survey was performed.', 'The average maximum gingival exposure was 5.52 \u00b1 1.64 mm preoperatively and significantly decreased to 1.79 \u00b1 0.67 mm at 6 months after surgery (P < 0.05) along with a significantly improved nasolabial angle from initially 85.3\u00b0 \u00b1 6.21\u00b0 to 95.2\u00b0 \u00b1 7.1\u00b0 (P < 0.05). The majority of patients (90.5%) rated their postoperative outcome as highly improved and improved. Temporary discomfort involving upper lip numbness, foreign body sensation, and stiff smiling expression was complained at 1 month postoperatively and gradually returned to normal after 3 months. No late recurrence or other complications were seen in any of the patients.",
            "output": [
                "Does correction of Midface Depression Using an Inverted m-shaped Expanded Polytetrafluoroethylene Implant improve Gingival Exposure?"
            ]
        },
        {
            "id": "task847-7306d647db6b435e830f2e3b6c5a4f81",
            "input": "Influenza vaccination is recommended for vulnerable individuals, including active drug users, to prevent influenza complications and decrease influenza spread. Recent studies suggest that opioids negatively regulate immune responses in experimental models, but the extent to which opioid use will affect the humoral responses to influenza vaccine in humans is unknown. This information is critical in maximizing vaccination efforts.', 'To determine whether there is a difference in antibody response after influenza vaccination in heroin or methadone users compared to control subjects.', 'We studied active heroin users, subjects on methadone maintenance treatment (MMT) and subjects that did not use any drugs before and 1 and 4 weeks after vaccination with trivalent influenza vaccine (TIV). We measured hemagglutination inhibition and microneutralization titers, and we compared geometric mean titers (GMT), and rates of seroprotection and seroconversion for each of the vaccine strains among the 3 groups of subjects.', 'Heroin users, subjects on MMT and non-user controls mount a similarly robust serologic response to TIV. GMT and rates of seroprotection and seroconversion were not significantly different among groups.",
            "output": [
                "Does active opioid use attenuate the humoral responses to inactivated influenza vaccine?"
            ]
        },
        {
            "id": "task847-1e23edfbd15a4269b16374a32376abe1",
            "input": "Atrial fibrillation (AF) is a common arrhythmia in heart failure (HF). Recent studies have shown that serum cancer antigen-125 (CA-125) levels are elevated in HF, and high levels of CA-125 in HF patients with sinus rhythm have been shown to be associated with the development of new onset AF. However, the relation between CA-125 levels and the presence of AF in HF is unknown. In this study we investigated whether plasma CA-125 levels in patients with systolic HF could predict the presence of AF.', 'The study was a retrospective cohort design including 205 stable systolic HF patients who were selected during outpatient clinic visits and who had CA-125 measurement and an electrocardiogram within the last one month before admittance to cardiology clinic. Patients were classified into two groups based on the presence of AF (n = 67) or sinus rhythm (n = 138).', 'The mean age of the patients was 68 \u00b1 11 years. CA-125 levels were significantly higher in patients with AF than patients with SR [33 (3-273) vs 102 (7-296) U/ml, P < 0.001]. CA-125 level, presence of right ventricular dilatation, pericardial effusion, moderate to severe TR and MR, and left atrial diameter were found to be associated with the presence of AF in univariate analysis. In a multivariate logistic regression model, only the CA-125 level remained associated. Also, according to the ROC curve analysis, the optimal cut-off level of CA-125 for predicting AF was \u2265 91 U/mL with a specificity of 84% and a sensitivity of 54%.",
            "output": [
                "Is higher cancer antigen 125 level associated with the presence of permanent atrial fibrillation in systolic heart failure patients?"
            ]
        },
        {
            "id": "task847-05f981aa8ab942f8a3d4afbfd0a8fbae",
            "input": "The aim of this study was to investigate whether renal sympathetic denervation (RSD) improves ventricular heart rate (HR) control in patients with persistent atrial fibrillation (AF).', 'Twenty-one patients (aged 57.5 \u00b1 10.2 years, 76.2% male) with persistent AF and hypertension underwent RSD and completed 7-days follow-up evaluations, including 24-hour Holter monitoring (Holter), blood pressure (BP), 24-hour ambulatory BP monitoring (ABPM). Patients were grouped into tertiles of average HR at baseline Holter recording for evaluation of RSD effects on atrioventricular (AV) node (group 1: HR \u2267 90 bpm; group 2: 80 bpm \u2266 HR < 90 bpm; group 3: HR < 80 bpm).', 'All patients successfully underwent RSD without any complications. The clinical and procedural characteristics were similar in all groups of patients. No significant changes in BP were observed in the three groups before and after RSD. Compared with baseline, the average HR (Holter) of patients in group 1, 2 and 3 had a reduction of 22.6 \u00b1 13.2 bpm (83.3 \u00b1 4.9 vs 106.0 \u00b1 14.6, P = 0.004), 9.7 \u00b1 7.8 bpm (75.7 \u00b1 7.6 vs 85.4 \u00b1 3.7, P = 0.017) and 2.3 \u00b1 2.9 bpm (71.4 \u00b1 4.0 vs 73.7 \u00b1 4.7, P = 0.089) at 7 days after RSD, respectively.",
            "output": [
                "Does renal sympathetic denervation improve rate control in patients with symptomatic persistent atrial fibrillation and hypertension?"
            ]
        },
        {
            "id": "task847-5aebead34c6442a48762489ef0b64f17",
            "input": "MicroRNA-208a (miR-208a) exacerbated cardiomyocyte apoptosis via inhibiting nemo-like kinase (NLK). miR-208a is a crucial molecule in the regulation of heart diseases, however, the biological function and underlying mechanism of miR-208a in the progression of cardiomyocyte apoptosis is not clearly elucidated. We hypothesized that miR-208a might potentiate cardiomyocyte apoptosis through inhibiting NLK.', 'Male Sprague-Dawley rats were underwent permanent coronary artery ligation to establish myocardial infarction (MI) model. The quantitative real-time RT-PCR (qRT-PCR) was used to evaluate the expression of miR-208a and NLK mRNA. Western blot was applied to detect NLK and Bcl-2 proteins expression. Luciferase reporter assay was performed to indentify NLK as a target of miR-208a. The apoptosis of H9C2 cells was assessed by flow cytometry (FCM).', 'miR-208a was upregulated accompanying with a significant decrease of NLK in response to MI, and stronger miR-208a staining was detected by in situ hybridization in the cytoplasm of cardiomyocytes in MI group compared to the sham group. In vitro, overexpression of miR-208a greatly enhance Ang II-induced the apoptosis of H9C2 cells through downregulating of NLK and the anti-apoptosis protein Bcl-2 expression, whereas these effects were reversed when miR-208a was downregulated. Dual luciferase reporter assay and western blot results demonstrated that NLK was a direct target of miR-208a. Interestingly, upregulation of NLK obviously increased Bcl-2 expression and reduced the percentage of apoptotic cells, while attenuation of NLK reduced the level of Bcl-2 and cells apoptosis after treatment with Ang II.",
            "output": [
                "Does microRNA-208a potentiate Angiotensin II-triggered Cardiac Myoblasts Apoptosis via Inhibiting Nemo-like Kinase ( NLK )?"
            ]
        },
        {
            "id": "task847-f1ad91503f9a47aeb10992b743c4c9f2",
            "input": "The crosstalk between skeletal muscle (SkM) and beta cells plays a role in diabetes aetiology. In this study, we have investigated whether SkM-released exosome-like vesicles (ELVs) can be taken up by pancreatic beta cells and can deliver functional cargoes.', 'Mice were fed for 16\\xa0weeks with standard chow diet (SCD) or with standard diet enriched with 20% palmitate (HPD) and ELVs were purified from quadriceps muscle. Fluorescent ELVs from HPD or SCD quadriceps were injected i.v. or intramuscularly (i.m.) into mice to determine their biodistributions. Micro (mi)RNA quantification in ELVs was determined using quantitative real-time RT-PCR (qRT-PCR)-based TaqMan low-density arrays. Microarray analyses were performed to determine whether standard diet ELVs (SD-ELVs) and high palmitate diet ELVs (HPD-ELVs) induced specific transcriptional signatures in MIN6B1 cells.', 'In vivo, muscle ELVs were taken up by pancreas, 24\\xa0h post-injection. In vitro, both SD-ELVs and HPD-ELVs transferred proteins and miRNAs to MIN6B1 cells and modulated gene expressions whereas only HPD-ELVs induced proliferation of MIN6B1 cells and isolated islets. Bioinformatic analyses suggested that transferred HPD-ELV miRNAs may participate in these effects. To validate this, we demonstrated that miR-16, which is overexpressed in HPD-ELVs, was transferred to MIN6B1 cells and regulated Ptch1, involved in pancreas development. In vivo, islets from HPD mice showed increased size and altered expression of genes involved in development, including Ptch1, suggesting that the effect of palm oil on islet size in vivo was reproduced in vitro by treating beta cells with HPD-ELVs.",
            "output": [
                "Do exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice?"
            ]
        },
        {
            "id": "task847-0affcf74acc944ae87a0f6f6dcc4d10f",
            "input": "The purpose of this study was to determine the yield and clinical impact of sacrum and coccyx radiographs in the emergency department (ED).', 'Consecutive sacrum and coccyx radiographs obtained in the EDs of four hospitals over a 6-year period were categorized as positive for acute fracture or dislocation, negative, or other. Five follow-up metrics were analyzed: follow-up advanced imaging in the same ED visit, follow-up advanced imaging within 30 days, new analgesic prescriptions, clinic follow-up, and surgical intervention within 60 days.', 'Sacrum and coccyx radiographs from 687 patients (mean age, 48.1 years; 61.6% women and 38.4% men) obtained at level-1 (n = 335) and level-2 (n = 352) trauma centers showed a positivity rate of 8.4% \u00b1 2.1% (n = 58/687). None of the 58 positive cases had surgical intervention. At the level-1 trauma centers, there was no significant association between sacrum and coccyx radiograph positivity and analgesic prescription or clinical follow-up (p = 0.12; odds ratio [OR], 2.3; 95% CI, 0.81-6.20). At the level-2 trauma centers, 97.1% (n = 34/35) of patients with positive sacrum and coccyx radiographs received analgesic prescriptions or clinical referrals, whereas negative cases were at 82.9% (OR, 7.0; 95% CI, 0.94-52.50). Of all cases, 5.7% (n = 39) and 4.3% (n = 29) had advanced imaging in the same ED visit and within 30 days, respectively. Sacrum and coccyx radiography results had no significant correlation with advanced imaging in the same ED visit (level-1, p = 0.351; level-2, p = 0.179). There was no significant difference in 30-day advanced imaging at the level-1 trauma centers (p = 0.8), but there was at the level-2 trauma centers (p = 0.0493).",
            "output": [
                "Do sacrum and Coccyx Radiographs Have Limited Clinical Impact in the Emergency Department?"
            ]
        },
        {
            "id": "task847-0d38b31dbec443739a563a3d25ad2153",
            "input": "The perineum stretches naturally during obstetrical labor, but it is unknown whether this stretch has a negative impact on pelvic floor outcomes after a vaginal birth (VB). We aimed to evaluate whether perineal stretch was associated with postpartum pelvic floor dysfunction, and we hypothesized that greater perineal stretch would correlate with worsened outcomes.', 'This was a prospective cohort study of primiparous women who had a VB. Perineal body (PB) length was measured antepartum, during labor, and 6\\xa0months postpartum. We determined the maximum PB (PBmax) measurements during the second stage of labor and PB change (\u0394PB) between time points. Women completed functional questionnaires and had a Pelvic Organ Prolapse Quantification (POP-Q) system exam 6\\xa0months postpartum. We analyzed the relationship of PB measurements to perineal lacerations and postpartum outcomes, including urinary, anal, and fecal incontinence, sexual activity and function, and POP-Q measurements.', 'Four hundred and forty-eight women with VB and a mean age of 24\\u2009\u00b1\\u20095.0\\xa0years with rare (5\\xa0%) third- or fourth-degree lacerations were assessed. During the second stage of labor, 270/448 (60\\xa0%) had perineal measurements. Mean antepartum PB length was 3.7\\u2009\u00b1\\u20090.8\\xa0cm, with a maximum mean PB length (PBmax) during the second stage of 6.1\\u2009\u00b1\\u20091.5\\xa0cm, an increase of 65\\xa0%. The change in PB length (\u0394PB) from antepartum to 6\\xa0months postpartum was a net decrease (-0.39\\u2009\u00b1\\u20091.02\\xa0cm). PB change and PBmax were not associated with perineal lacerations or outcomes postpartum (all p\\u2009>\\u20090.05).",
            "output": [
                "Does perineal body stretch during labor predict perineal laceration , postpartum incontinence , or postpartum sexual function : a cohort study?"
            ]
        },
        {
            "id": "task847-d780f0164b334beb98102ab18c4e0f4c",
            "input": "Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion.', 'We performed a nested case-control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD).', 'There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects.",
            "output": [
                "Is the relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation modified by donor smoking and reperfusion hyperoxia?"
            ]
        },
        {
            "id": "task847-2a6d938ffb9240159a6eb8428a2a6e97",
            "input": "Adenosine monophosphate-activated protein kinases (AMPKs), as a sensor of cellular energy status, have been known to play an important role in the pathophysiology of diabetes and its complications. Because AMPKs are known to be expressed in podocytes, it is possible that podocyte AMPKs could be an important contributing factor in the development of diabetic proteinuria. We investigated the roles of AMPKs in the pathological changes in podocytes induced by high-glucose (HG) and advanced glycosylation end products (AGEs) in diabetic proteinuria.', 'We prepared streptozotocin-induced diabetic renal tissues and cultured rat and mouse podocytes under diabetic conditions with AMPK-modulating agents. The changes in AMPK\u03b1 were analyzed with confocal imaging and Western blotting under the following conditions: (1) normal glucose (5mM, =control); (2) HG (30mM); (3) AGE-added; or (4) HG plus AGE-added.', 'The density of glomerularphospho-AMPK\u03b1 in experimental diabetic nephropathy decreased as a function of the diabetic duration. Diabetic conditions including HG and AGE changed the localization of phospho-AMPK\u03b1 from peripheral cytoplasm to internal cytoplasm and peri- and intranuclear areas in podocytes. HG reduced the AMPK\u03b1 (Thr172) phosphorylation of rat podocytes, and similarly, AGEs reduced the AMPK\u03b1 (Thr172) phosphorylation of mouse podocytes. The distributional and quantitative changes in phospho-AMPK\u03b1 caused by diabetic conditions were preventable using AMPK activators, metformin, and 5-aminoimidazole-4-carboxamide-1\u03b2-riboside.",
            "output": [
                "Do diabetic conditions modulate the adenosine monophosphate-activated protein kinase of podocytes?"
            ]
        },
        {
            "id": "task847-b75b74a639584539811ee00ebbfce981",
            "input": "Gait kinematics and kinetics of the knee before and after medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent lateral patellar dislocation (RPD) are unknown. The purpose of this study was to measure knee kinematics and kinetics during gait before and 1\\xa0year after anatomical MPFL reconstruction in patients with RPD and compare the results to healthy individuals.', 'Eleven RPD patients were treated using an anatomical MPFL reconstruction procedure. Gait analysis was conducted before and at 3, 6, and 12\\xa0months after surgery. For comparison, 15 healthy volunteers with no history of orthopaedic problems in their lower limbs were included as the control group. Knee kinematics and kinetics were analysed during gait.', 'Before surgery, the internal knee extension moment in RPD patients was significantly lower than in controls (P\\xa0=\\xa00.025). At 3\\xa0months post-operatively, there was an additional decrease in knee extension moment compared to before surgery, and so it was still significantly lower than in the control group (P\\xa0<\\xa00.01). One\\xa0year post-operatively, knee extension moment in the RPD group was significantly increased compared to 3\\xa0months post-operatively (P\\xa0<\\xa00.01). The knee flexion angle in the early stance phase in the RPD group at 3\\xa0months post-operatively was significantly lower than that of controls (P\\xa0<\\xa00.01). Knee kinematics and kinetics were similar to that of controls 1\\xa0year after surgery.",
            "output": [
                "Are knee biomechanics during walking in recurrent lateral patellar dislocation normalized by 1 year after medial patellofemoral ligament reconstruction?"
            ]
        },
        {
            "id": "task847-490b5cbe21b14f4492ba1f971d12ba98",
            "input": "The purpose of the present study was to compare the change in tibial posterior slope angle (PSA) between patients treated via computer-assisted and conventional closed-wedge high tibial osteotomy (CWHTO). It was hypothesized that a decrease in the PSA would be less in the computer-assisted group than in the conventional group.', 'Data on a total of 75 computer-assisted CWHTOs (60 patients) and 75 conventional CWHTOs (49 patients) were retrospectively compared using matched pair analysis. The pre- and postoperative mechanical axis (MA) and the PSA were radiographically evaluated. The parallel angle was defined as the angle between the joint line and the osteotomy surface. The data were compared between the two groups.', 'The postoperative radiographic MA averaged 1.3\u00b0\\xa0\u00b1\\xa02.6\u00b0 valgus in the computer-assisted group and 0.3\u00b0\\xa0\u00b1\\xa03.1\u00b0 varus in the conventional group. The change in PSA averaged -0.8\u00b0\\xa0\u00b1\\xa00.9\u00b0 in the computer-assisted group and -4.0\u00b0\\xa0\u00b1\\xa02.2\u00b0 in the conventional group. The parallel angle averaged 0.2\u00b0\\xa0\u00b1\\xa03.0\u00b0 in the computer-assisted group and 6.2\u00b0\\xa0\u00b1\\xa05.3\u00b0 in the conventional group.",
            "output": [
                "Does computer-assisted navigation decrease the change in the tibial posterior slope angle after closed-wedge high tibial osteotomy?"
            ]
        },
        {
            "id": "task847-155a7ec06d734a2882bc6fc61d8a1c22",
            "input": "The aim of this research was to assess the effect of mouth rinses with and without alcohol on the hardness of dental nano-filled composite.', \"The micro-hardness of fifty circular disk shaped specimens of 7 mm x 2 mm were measured after 14 days. Specimens were immersed into alcohol containing (Listerine and Colgate Perioguard) and alcohol-free (Prodent and Sensodyne Oral antiseptic) mouth rinse solutions. Artificial saliva served as the control. Vickers Micro-hardness was measured with a 30gram load for 30 seconds dwell time by using a diamond indenter. Significant differences were represented by p<0.05, whereas highly significant difference represented by p<0.01. The level of significance (p) was calculated with the help of repeated measure ANOVA. For multiple comparisons, Tukey's multiple comparison test was used.\", 'Statistical analysis revealed highly significant difference between specimens immersed in artificial saliva (control) and Listerine (p<0.01). Whereas significant difference were observed between control and Colgate Periogard (p<0.05). However, no significant difference was observed on comparing Prodent and Sensodyne Oral antiseptic mouth rinses with control group(p>0.05). Control specimens depicted highest value of micro-hardness(60.5746 \u00b1 3.2703) compared to the lowest value seen in specimens immersed in Listerine solvent(54.4687 \u00b1 1.0937).",
            "output": [
                "Does influence of mouth rinse on the surface hardness of dental resin nano-composite?"
            ]
        },
        {
            "id": "task847-74cbad40392e41eba77d15167e40694f",
            "input": "Ovarian tissue preservation is proposed to patients at risk of premature ovarian failure, but this procedure still needs to be optimized. To limit injury during ovarian tissue cryopreservation, anti-apoptotic drugs were added to the transport and freezing media of ovarian cortex tissue.', 'Sheep ovaries were transported, prepared and frozen in solutions containing vehicle or anti-apoptotic drugs (Z-VAD-FMK, a pan-caspase inhibitor, or sphingosine-1-phosphate (S1P), a bioactive lipid). After the tissue was thawed, the ovarian cortex was cultured for 2 or 6 days. Follicular quantification and morphological and proliferation analyses were performed on histological sections.', 'After 2 days of culture, S1P improved the quality of primordial follicles; higher densities of morphologically normal and proliferative primordial follicles were found. Z-VAD-FMK displayed similar effects by preserving global primordial follicular density, but this effect was evident after 6 days of culture. This drug also improved cell proliferation after 2 and 6 days of culture.",
            "output": [
                "Does supplementation of transport and freezing media with anti-apoptotic drugs improve ovarian cortex survival?"
            ]
        },
        {
            "id": "task847-fc91eae82642439fb8ea3abae87eddce",
            "input": "Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug resistance genes is an important component of drug resistance mechanisms in vitro, their clinical relevance remains to be determined. Therefore, identifying pathways that could be targeted in the clinic to eliminate anthracycline-resistant breast cancer remains a major challenge.', 'We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 and ZR-75-1 epirubicin-resistant breast cancer cell lines to identify pathways contributing to anthracycline resistance. Native cell lines were exposed to increasing concentrations of epirubicin until resistant cells were generated. To identify mechanisms driving epirubicin resistance, we used a complementary approach including gene expression analyses to identify molecular pathways involved in resistance, and small-molecule inhibitors to reverse resistance. In addition, we tested its clinical relevance in a BR9601 adjuvant clinical trial.', 'Characterisation of epirubicin-resistant cells revealed that they were cross-resistant to doxorubicin and SN-38 and had alterations in apoptosis and cell-cycle profiles. Gene expression analysis identified deregulation of histone H2A and H2B genes in all four cell lines. Histone deacetylase small-molecule inhibitors reversed resistance and were cytotoxic for epirubicin-resistant cell lines, confirming that histone pathways are associated with epirubicin resistance. Gene expression of a novel 18-gene histone pathway module analysis of the BR9601 adjuvant clinical trial revealed that patients with low expression of the 18-gene histone module benefited from anthracycline treatment more than those with high expression (hazard ratio 0.35, 95\\xa0% confidence interval 0.13-0.96, p\\u2009=\\u20090.042).",
            "output": [
                "Is downregulation of histone H2A and H2B pathways associated with anthracycline sensitivity in breast cancer?"
            ]
        },
        {
            "id": "task847-55ee43fe75f74d9d8101a4a2970dbee7",
            "input": "We evaluated the efficacy and safety of amifampridine phosphate (Firdapse(\u00ae)) for symptomatic treatment in Lambert-Eaton myasthenic syndrome (LEMS).', 'Phase 3, randomized, double-blind, study. Patients were treated initially with amifampridine phosphate for 7-91 days, followed by randomization to continue amifampridine phosphate for 14 days or placebo (7-day taper, 7-day placebo). The primary efficacy endpoints were changes from baseline at day 14 in Quantitative Myasthenia Gravis and Subject Global Impression scores.', 'The coprimary efficacy end points and 1 of the secondary efficacy end points were met, showing a significant benefit of aminfampridine phosphate over placebo at Day 14. All 5 primary, secondary, and tertiary endpoints achieved statistical significance at Day 8. Amifampridine phosphate was well tolerated; the most common adverse events were oral and digital paresthesias, nausea, and headache.",
            "output": [
                "Is amifampridine phosphate ( Firdapse ( \u00ae ) ) effective and safe in a phase 3 clinical trial in LEMS?"
            ]
        },
        {
            "id": "task847-75b8a5368ab8446bb1497a8251801813",
            "input": "Neuroinflammation associated with advanced human immunodeficiency virus (HIV)-1 infection is often exacerbated by chronic cocaine abuse. Cocaine exposure has been demonstrated to mediate up-regulation of inflammatory mediators in in vitro cultures of microglia. The molecular mechanisms involved in this process, however, remain poorly understood. In this study, we sought to explore the underlying signaling pathways involved in cocaine-mediated activation of microglial cells.', 'BV2 microglial cells were exposed to cocaine and assessed for toll-like receptor (TLR2) expression by quantitative polymerase chain reaction (qPCR), western blot, flow cytometry, and immunofluorescence staining. The mRNA and protein levels of cytokines (TNF\u03b1, IL-6, MCP-1) were detected by qPCR and ELISA, respectively; level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection kit; activation of endoplasmic reticulum (ER)-stress pathways were detected by western blot. Chromatin immunoprecipitation (ChIP) assay was employed to discern the binding of activating transcription factor 4 (ATF4) with the TLR2 promoter. Immunoprecipitation followed by western blotting with tyrosine antibody was used to determine phosphorylation of TLR2. Cocaine-mediated up-regulation of TLR2 expression and microglial activation was validated in cocaine-injected mice.', 'Exposure of microglial cells to cocaine resulted in increased expression of TLR2 with a concomitant induction of microglial activation. Furthermore, this effect was mediated by NADPH oxidase-mediated rapid accumulation of ROS with downstream activation of the ER-stress pathways as evidenced by the fact that cocaine exposure led to up-regulation of pPERK/peIF2\u03b1/ATF4 and TLR2. The novel role of ATF4 in the regulation of TLR2 expression was confirmed using genetic and pharmacological approaches.",
            "output": [
                "Does cocaine-mediated induction of microglial activation involve the ER stress-TLR2 axis?"
            ]
        },
        {
            "id": "task847-dea92a2033c04e50a659b41458a6164b",
            "input": "Tumor cell migration and diffuse infiltration into brain parenchyma are known causes of recurrence after treatment in glioblastoma (GBM), mediated in part by the interaction of glioma cells with the extracellular matrix, followed by degradation of matrix by tumor cell derived proteases, particularly the matrix metalloproteinases (MMP). Sevoflurane and thiopental are anesthetics commonly used in cancer surgery. However, their effect on the progression of glioma cells remains unclear. The aim of this study was to explore the role of these anesthetics on the migration and activity of MMP-2 in glioma cells.', 'Cultured U87MG cells were pretreated with sevoflurane or thiopental and in vitro wound healing scratch assay was carried out to analyze their effect on migration of these cells. Gelatin zymography was carried out to examine the effect of these anesthetics on tumor cell MMP-2 activity using the conditioned media 24 h after pretreatment. Cell viability was analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay.', 'U87MG cells exposed to 2.5% sevoflurane or different concentrations of thiopental significantly decreased migration and activity of MMP-2 compared to control. No effect was seen on the viability of these cells after pretreatment with sevoflurane or thiopental.",
            "output": [
                "Does sevoflurane and thiopental preconditioning attenuate the migration and activity of MMP-2 in U87MG glioma cells?"
            ]
        },
        {
            "id": "task847-d5d0079b41c34cf5a137c8c395f525e4",
            "input": "Apoptosis participated in the pathological process of myocardial ischemia/reperfusion (I/R) injury. Previous studies have reported that endogenous substance sRAGE protect against I/R injury through inhibiting myocardial apoptosis. But the mechanisms are currently unknown. Prior work has demonstrated that ubiquitin proteasome system (UPS) dysfunction is closely related to apoptosis. We explored the potential role of UPS in the effect of sRAGE inhibition on I/R-induced myocardial apoptosis.', 'Adult male C57BL mice treated with sRAGE (100\u03bcg/day, i.p.) or saline were performed to ligate left anterior descending coronary artery (LAD) as an in vivo model. As an in vitro model, primary murine cardiomyocytes pretreated with sRAGE or sRAGE-containing adenovirus were simulated I/R by \"ischemia buffer\". The TUNEL and caspase-3 activity were assessed. Also the activity and expression of proteasome were detected. sRAGE decreased the number of TUNEL-positive cardiomyocytes and caspase-3 activity, however, the inhibition of sRAGE on I/R-induced apoptosis was abolished by proteasome inhibitor Bortezimb (BTZ). sRAGE inhibited the decreased proteasome activity, also the reduction in protein and gene levels of \u03b21i and \u03b25i following I/R. Suppression of STAT3 blocked the inhibition of sRAGE on apoptosis induced by I/R. The chromatin immunoprecipitation (CHIP) results confirmed that sRAGE promoted activating STAT3 binding to \u03b21i and \u03b25i promoter.",
            "output": [
                "Does soluble receptor for advanced glycation end-products protect against ischemia/reperfusion-induced myocardial apoptosis via regulating the ubiquitin proteasome system?"
            ]
        },
        {
            "id": "task847-45c8be47b6d04c4ba66ad0d589642991",
            "input": "Adjuvant imatinib is useful in patients with gastrointestinal stromal tumors (GIST) at high risk of recurrence. At present, the risk of recurrence is determined based on tumor size, mitotic rate, tumor site, and tumor rupture. Previous studies using various biochemical pathways identified gene expression patterns that distinguish two subsets of aggressive fibromatosis (AF), serous ovarian carcinoma (OVCA), and clear cell renal cell carcinoma (RCC). These gene sets separated soft tissue sarcomas into two groups with different probabilities of developing metastatic disease. The present study used these gene sets to identify GIST subgroups with different probabilities of developing metastatic disease.', 'We utilized these three gene sets, hierarchical clustering, and Kaplan-Meier analysis, to examine 60 primary resected GIST samples using Agilent chip expression profiling.', 'Hierarchical clustering using both the combined and individual AF-, OVCA-, and RCC- gene sets identified differences in probabilities of developing metastatic disease between the clusters defined by the first branch point of the clustering dendrograms (p = 0.029 for the combined gene set, p = 0.003 for the AF-gene set, p < 0.001 for the OVCA-gene set, and p = 0.003 for the RCC-gene set).",
            "output": [
                "Does gene expression identify heterogeneity of metastatic behavior among gastrointestinal stromal tumors?"
            ]
        },
        {
            "id": "task847-2d74bc55ca6d45dfa3a491295489ee7a",
            "input": "According to previous studies, sulodexide suppresses intravascular inflammation when used in patients with chronic venous disease (CVD). In the current study, we tested the effect of prolonged in vitro exposure of human venous endothelial cells to the serum from patients with CVD, examining the function of these cells and how it is modified when these cells are simultaneously exposed to sulodexide.', 'Human umbilical venous cells (HUVEC) were cultured in standard medium (control), in medium supplemented with 5% serum pooled from CVD patients (CVD-serum) or in medium from CVD patients who were treated with sulodexide (CVD-serum-SUL). The synthesis of interleukin-6 (IL-6), monocyte chemoattractant protein -1(MCP-1) and soluble intercellular adhesion molecule - 1 (s-ICAM-1) were studied at the beginning of incubation and were measured after 9 and 15 days of exposure to the studied media. The concentration of IL-6 after cell stimulation by interleukin -1 (IL-1) was also measured. In a subsequent part of the experiment, the effect of the studied sera on the in vitro replicative ageing of HUVEC was evaluated. A total of 15 passages of the cell culture were performed and both the PDT (population doubling time) and the cell hypertrophy were assessed.', 'The concentrations of Il-6, MCP-1, and ICAM-1 gradually increased in the supernatants containing 5% CVD serum compared with the control medium. In the supernatants obtained after cell incubation with serum from sulodexide treated patients, the increase in concentrations of IL-6, MCP-1 and ICAM-1 was significantly less than the control. Release of IL-6 after stimulation with IL-1 (100 pg/mL) was the highest in the CVD-serum group: 3540\u00b1670 pg/105 cells vs. 1850\u00b1540 pg/105 cells in the control (P<0.01 vs. CVD-serum) and 2320 \u00b1430 pg/105 cells in CVD-serum-SUL (P<0.02 vs. CVD-serum). PDT was significantly longer in the cells incubated with CVD serum compared with the control group, and PDT was reduced when serum from sulodexide treated patients was used. The cells became senescent in the presence of CVD serum, but the cells obtained from patients at the end of 8 weeks of treatment with sulodexide showed a much weaker inflammatory phenotype than the CVD group.",
            "output": [
                "Does sulodexide reduce the inflammatory reaction and senescence of endothelial cells in conditions involving chronic venous disease?"
            ]
        },
        {
            "id": "task847-eec56b007f3741ff85fce1961290b990",
            "input": "Ninety-six male adult CD-1 mice were randomly divided into sham, spinal cord injury (SCI)\\u200a+\\u200avehicle, and SCI\\u200a+\\u200aIPA-3 groups. Expression of matrix metalloproteinase (MMP)-2 and MMP-9, production of tumor necrosis factors (TNF)-\u03b1 and interleukin (IL)-1\u03b2, tissue edema, blood-spinal cord barrier penetrability, neural cell apoptosis, and neurological function recovery were measured.', 'The aim of the study was to evaluate the effect of specific inhibition of p21-activated kinase 1 (PAK1) by IPA-3 on SCI and the underlying mechanisms thereof.', 'SCI is a devastating clinical condition that may result in long-lasting and deteriorating functional deficits. The major goal of SCI treatment is to limit the development of secondary injury. IPA-3, a PAK1 inhibitor, exhibited neuroprotection against secondary damage after traumatic brain injury and subarachnoid hemorrhage (SAH).', 'MMP-2, MMP-9, and cleaved caspase-3 expression were assessed by Western blot. Inflammatory cytokines TNF-\u03b1 and IL-1\u03b2 were detected by enzyme-linked immunosorbent assay (ELISA). The blood-spinal cord barrier disruption was measured by water content and Evans blue extravasation of the spinal cord. Neuronal apoptosis was evaluated by Nissl staining and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay. The locomotor behavior of hind limb was evaluated by Basso Mouse Scale (BMS) at 1, 3, 7, 14, and 28 days post-injury.', 'Compared with SCI\\u200a+\\u200avehicle mice, IPA-3 treatment showed decreased p-PAK1, MMP-2, MMP-9, cleaved caspase-3, TNF-\u03b1, and IL-1\u03b2 expression. Moreover, inhibition of PAK1 by IPA-3 reduced spinal cord water content and Evans blue extravasation, increased neuronal survival, and reduced TUNEL-positive cells at 24 hours after SCI. Furthermore, IPA-3 improved spinal cord functional recovery 7 days after SCI.",
            "output": [
                "Does inhibition of p21-Activated Kinase 1 by IPA-3 promote Locomotor Recovery After Spinal Cord Injury in Mice?"
            ]
        },
        {
            "id": "task847-790231ebd2744808aad4c8a1daf5e1a2",
            "input": "The biomarker suppression of tumorigenicity 2 (ST2) is a well-established clinical biomarker of cardiac strain and is frequently elevated in a variety of cardiac conditions. Here, we sought to evaluate the prognostic value of ST2 in critically ill medical intensive care unit (MICU) patients without primary cardiac illness.', 'We measured ST2 and high-sensitivity troponin T (hsTnT) on plasma specimens collected on 441 patients following admission to a noncardiac MICU and evaluated the prognostic power of ST2 both alone and in multivariate models.', 'Of these critically ill patients, 96% exhibited ST2 concentrations above the reference interval. ST2 concentrations were highly predictive of intensive care unit and hospital length of stay, as well as in-hospital mortality, with high concentrations predicting a poor prognosis. Rates of in-hospital mortality were more than four times higher in patients with ST2 concentrations in the highest compared with the lowest quartile. In multivariate analysis, ST2 remained an important predictor of death after adjustment for age, hsTnT, and common diagnoses.",
            "output": [
                "Does sT2 predict Mortality and Length of Stay in a Critically Ill Noncardiac Intensive Care Unit Population?"
            ]
        },
        {
            "id": "task847-83f7c5e6cf734ea0affe888e163293e9",
            "input": "Astrocytes are critical for the development of postoperative cognitive dysfunction (POCD). In addition, astrocytes express toll-like receptors 4 (TLR4) and build up responses to innate immune triggers by releasing pro-inflammatory molecules. The pathogenesis of neurological disorders often involves the activation of astrocytes and associated inflammatory processes. Lithium, a primary drug for the treatment of bipolar disorder, has recently been suggested to have a role in neuroprotection during neurodegenerative diseases. In this study, we aimed to investigate whether lithium can ameliorate LPS-induced astrocytes activation via inhibition of TLR4 expression.', 'Primary astrocytes cells were pretreated with lithium and stimulated with lipopolysaccharide (LPS). Cellular activation, cytokine production, and TLR4 expression, were assessed.', 'Lithium significantly inhibited LPS-induced astrocytes activation and pro-inflammatory cytokine production, as well as LPS-induced TLR4 expression.",
            "output": [
                "Does lithium ameliorate LPS-Induced Astrocytes Activation Partly via Inhibition of Toll-Like Receptor 4 Expression?"
            ]
        },
        {
            "id": "task847-976a191832d3452fb4fbd6b80f699f24",
            "input": "Cognitive decline is part of the long-term outcome for many individuals with bipolar disorder (BD). The \u03b54 allele (APOE*4) of apolipoprotein E (APOE) is a well-established risk factor for dementia in Alzheimer's disease (AD). However, its contribution to the risk of cognitive deterioration in BD has not yet been determined. Our aim was to analyze the APOE genotype association with cognitive status in a sample of older adults with BD and compare this to the association in individuals with AD, individuals with mild cognitive impairment (MCI), and healthy controls.\", \"Participants (n\\xa0=\\xa0475) were allocated to four groups: individuals with BD (n\\xa0=\\xa077), those with AD (n\\xa0=\\xa0211), those with MCI (n\\xa0=\\xa043), and healthy controls (n\\xa0=\\xa0144) according to clinical and neuropsychological assessment. APOE was genotyped by real-time polymerase chain reaction. Tukey's honest significant difference test and Pearson's chi-squared test were used to compare diagnostic groups.\", 'Subjects with BD were similar to controls with respect to the distribution of the APOE genotype (p\\xa0=\\xa00.636) and allele frequencies (p\\xa0=\\xa00.481). Significant differences were found when comparing the AD group to the BD group or to controls (APOE genotype: p\\xa0<\\xa00.0002; allele frequencies: p\\xa0<\\xa00.001). APOE*4 was significantly increased in the AD group when compared to the BD group (p\\xa0=\\xa00.031) and controls (p\\xa0<\\xa00.0001). The cognitively impaired BD subgroup (Mini-Mental State Examination below the cutoff score and/or neuropsychological assessment compatible with MCI) had a statistically significant higher frequency of APOE*2 compared to the AD group (p\\xa0=\\xa00.003).",
            "output": [
                "Is apolipoprotein E genotype associated with cognitive impairment in older adults with bipolar disorder?"
            ]
        },
        {
            "id": "task847-6af9b0fd7c4f44cd91d26482714e5492",
            "input": "The aim of the study was to calculate benchmark dose for chromosomal damage and reduced white blood cell (WBC) associated with exposure to benzene (BZ).', 'A group of 317 exposed workers and 102 controls were examined for WBC count and genotoxicity by micronucleus (MN) frequency. The cumulative exposure concentration of BZ was calculated by ambient air BZ concentration at worksites in conjunction with job type and associated service duration.', 'MN frequency (P\\u200a<\\u200a0.01) was higher and WBC count was lower (P\\u200a<\\u200a0.01) in exposed workers on average than in the controls. MN frequency was a more sensitive than WBC; workers older than 30 were more susceptible to abnormal MN frequency and WBC count reduction than those younger than 30.",
            "output": [
                "Does benchmark dose Based on Abnormality of WBC or Micronucleus Frequency in Benzene-Exposed Chinese Workers?"
            ]
        },
        {
            "id": "task847-256407a5f877486db3e847a24a3c3996",
            "input": "Chromatin epigenetics participate in control of gene expression during metazoan development. DNA methylation and post-translational modifications (PTMs) of histones have been extensively characterised in cell types present in, or derived from, mouse embryos. In embryonic stem cells (ESCs) derived from blastocysts, factors involved in deposition of epigenetic marks regulate properties related to self-renewal and pluripotency. In the germ lineage, changes in histone PTMs and DNA demethylation occur during formation of the primordial germ cells (PGCs) to reset the epigenome of the future gametes. Trimethylation of histone H3 on lysine 27 (H3K27me3) by Polycomb group proteins is involved in several epigenome-remodelling steps, but it remains unclear whether these epigenetic features are conserved in non-mammalian vertebrates. To investigate this question, we compared the abundance and nuclear distribution of the main histone PTMs, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in chicken ESCs, PGCs and blastodermal cells (BCs) with differentiated chicken ESCs and embryonic fibroblasts. In addition, we analysed the expression of chromatin modifier genes to better understand the establishment and dynamics of chromatin epigenetic profiles.', 'The nuclear distributions of most PTMs and 5hmC in chicken stem cells were similar to what has been described for mammalian cells. However, unlike mouse pericentric heterochromatin (PCH), chicken ESC PCH contained high levels of trimethylated histone H3 on lysine 27 (H3K27me3). In differentiated chicken cells, PCH was less enriched in H3K27me3 relative to chromatin overall. In PGCs, the H3K27me3 global level was greatly reduced, whereas the H3K9me3 level was elevated. Most chromatin modifier genes known in mammals were expressed in chicken ESCs, PGCs and BCs. Genes presumably involved in de novo DNA methylation were very highly expressed. DNMT3B and HELLS/SMARCA6 were highly expressed in chicken ESCs, PGCs and BCs compared to differentiated chicken ESCs and embryonic fibroblasts, and DNMT3A was strongly expressed in ESCs, differentiated ESCs and BCs.",
            "output": [
                "Do chicken embryonic stem cells and primordial germ cells display different heterochromatic histone marks than their mammalian counterparts?"
            ]
        },
        {
            "id": "task847-126ca3ad3660464588e65593d6880a5a",
            "input": "To quantify functional age-related changes in the cartilage antioxidant network in order to discover novel mediators of cartilage oxidative stress and osteoarthritis (OA) pathophysiology.', 'We evaluated histopathologic changes of knee OA in 10-, 20-, and 30-month-old male F344BN rats and analyzed cartilage oxidation according to the ratio of reduced to oxidized glutathione. Antioxidant gene expression and protein abundance were analyzed by quantitative reverse transcription-polymerase chain reaction and selected reaction-monitoring mass spectrometry, respectively. Superoxide dismutase 2 (SOD2) activity and acetylation were analyzed by colorimetric enzyme assays and Western blotting, respectively. We examined human OA cartilage to evaluate the clinical relevance of SOD2 acetylation, and we tested age-related changes in the mitochondrial deacetylase sirtuin 3 (SIRT-3) in rats and mice.', 'Cartilage oxidation and OA severity in F344BN rats increased with age and were associated with an increase in SOD2 expression and protein abundance. However, SOD2-specific activity decreased with age due to elevated posttranslational lysine acetylation. Consistent with these findings, SIRT-3 levels decreased substantially with age, and treatment with SIRT-3 increased SOD2 activity in an age-dependent manner. SOD2 was also acetylated in human OA cartilage, and activity was increased with SIRT-3 treatment. Moreover, in C57BL/6J mice, cartilage SIRT-3 expression decreased with age, and whole-body deletion of SIRT-3 accelerated the development of knee OA.",
            "output": [
                "Does aging promote Sirtuin 3-Dependent Cartilage Superoxide Dismutase 2 Acetylation and Osteoarthritis?"
            ]
        },
        {
            "id": "task847-8f5a8efe43fc4094be2b2667a4af86f3",
            "input": "Grass carp reovirus (GCRV) is responsible for viral hemorrhagic disease in cultured grass carp (Ctenopharyngon idellus). GCRV is a non-enveloped, double-stranded RNA virus in the genus Aquareovirus, of the family Reoviridae, which encodes seven structural proteins (VP1-VP7) and five nonstructural proteins (NS80, NS38, NS31, NS26, and NS16). To date, the mechanism of GCRV entry into CIK Ctenopharyngon idellus kidney (CIK) cells remains poorly understood.', 'Here, we present a study of the GCRV internalization mechanism in CIK cells. Our results indicated that GCRV infection was inhibited by chlorpromazine, the specific inhibitor for clathrin-mediated endocytosis. Colocalization of GCRV virions with endogenous clathrin was observed during early infection by confocal microscopy. Moreover, GCRV infection of CIK cells depended on acidification of the endosome. This was indicated by significant inhibition of viral infection following prophylactic treatment with the lysosomotropic drugs chloroquine or ammonium chloride. In addition, the disturbance of dynamin activity blocked GCRV entry, which confirmed the dynamin-dependent nature of clathrin-mediated endocytosis.",
            "output": [
                "Does disruption of clathrin-dependent trafficking result in the failure of grass carp reovirus cellular entry?"
            ]
        },
        {
            "id": "task847-07e2373710cf4a5b9fb40e56d50ec47e",
            "input": "Studies on the accuracy of microRNAs (miRNAs) in diagnosing non-small cell lung cancer (NSCLC) have still controversial. Therefore, we conduct to systematically identify miRNAs related to NSCLC, and their target genes expression changes using microarray data sets.', 'We screened out five miRNAs and six genes microarray data sets that contained miRNAs and genes expression in NSCLC from Gene Expression Omnibus.', 'Our analysis results indicated that fourteen miRNAs were significantly dysregulated in NSCLC. Five of them were up-regulated (miR-9, miR-708, miR-296-3p, miR-892b, miR-140-5P) while nine were down-regulated (miR-584, miR-218, miR-30b, miR-522, miR486-5P, miR-34c-3p, miR-34b, miR-516b, miR-592). The integrating diagnosis sensitivity (SE) and specificity (SP) were 82.6% and 89.9%, respectively. We also found that 4 target genes (p < 0.05, fold change > 2.0) were significant correlation with the 14 discovered miRNAs, and the classifiers we built from one training set predicted the validation set with higher accuracy (SE = 0.987, SP = 0.824).",
            "output": [
                "Does integrative microRNA and gene profiling data analysis reveal novel biomarkers and mechanisms for lung cancer?"
            ]
        },
        {
            "id": "task847-a97f26d4f6f244c29c96de4e87e7983b",
            "input": "Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality.', 'Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n=470). Primary care patients were followed for 13years (from 1999); the 5-year all-cause and cardiovascular mortality was used as end point.', 'In univariate analysis, patients in the 4th CCK quartile had an increased risk of 5-year cardiovascular mortality (hazard ratio 3.9, 95% confidence interval: 2.1-7.0, p<0.0001). In multivariate analysis including established factors associated with cardiovascular mortality, CCK concentrations in the 4th quartile were still associated with increased 5-year cardiovascular mortality risk (HR 3.1, 95% C.I.: 1.7-5.7, p=0.0004), even when including 4th quartile NT-proBNP concentrations in the same model. We observed a marked difference between the genders, where CCK concentrations in the 4th quartile were associated with a higher 5-year cardiovascular mortality in female patients (HR 8.99, 95% C.I.: 3.49-102.82, p=0.0007) compared to men (1.47, 95% C.I.: 0.7-3.3, p=0.35). In contrast, no significant information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk.",
            "output": [
                "Does cholecystokinin in plasma predict cardiovascular mortality in elderly females?"
            ]
        },
        {
            "id": "task847-bb5fc85a657146c18da47841e737a72d",
            "input": "To test whether intraarticular corticosteroid injection mitigates injury-induced synovitis and collagen degradation after anterior cruciate ligament transection (ACLT) and to characterize the synovial response using a functional genomics approach in a preclinical model of posttraumatic osteoarthritis.', 'Yorkshire pigs underwent unilateral ACLT without subsequent corticosteroid injection (the ACLT group; n\\u2009=\\u20096) or ACLT with immediate injection of 20 mg triamcinolone acetonide (the steroid group; n\\u2009=\\u20096). A control group of pigs (the intact group; n\\u2009=\\u20096) did not undergo surgery. Total synovial membrane cellularity and synovial fluid concentration of C1,2C neoepitope-bearing collagen fragments 14 days after injury were primary end points and were compared between the ACLT, steroid, and intact groups. Cells were differentiated by histologic phenotype and counted, while RNA sequencing was used to quantify transcriptome-wide gene expression and monocyte, macrophage, and lymphocyte markers.', 'In the intact group, total cellularity was 13% (95% confidence interval [95% CI] 9-16) and the C1,2C concentration was 0.24 \u03bcg/ml (95% CI 0.08-0.39). In the ACLT group, significant increases were observed in total cellularity (to 21% [95% CI 16-27]) and C1,2C concentration (to 0.49 \u03bcg/ml [95% CI 0.39-0.59]). Compared to values in the ACLT group, total cellularity in the steroid group was nonsignificantly decreased to 17% (95% CI 15-18) (P\\u2009=\\u20090.26) and C1,2C concentration in the steroid group was significantly decreased to 0.29 \u03bcg/ml (95% CI 0.23-0.35) (P\\u2009=\\u20090.04). A total of 255 protein-coding transcripts were differentially expressed between the ACLT group and the intact group. These genes mainly enriched pathways related to cellular immune response, proteolysis, and angiogenesis. Mononuclear leukocytes were the dominant cell type in cell-dense areas. MARCO, SOCS3, CCR1, IL4R, and MMP2 expression was significantly associated with C1,2C levels.",
            "output": [
                "Does immediate Administration of Intraarticular Triamcinolone Acetonide After Joint Injury modulate Molecular Outcomes Associated With Early Synovitis?"
            ]
        },
        {
            "id": "task847-0b024494268c46108c9a3f80539294d5",
            "input": "Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far.', 'Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed.', 'At 12 months, the mean BLL of infants was 7.41 \u03bcg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 \u03bcg/dL. Lead poisoning, defined as BLL>10 \u03bcg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators.",
            "output": [
                "Do elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants?"
            ]
        },
        {
            "id": "task847-f5de8856c7354536ac83f991c4d93a4e",
            "input": "Oxidative stress is central to the pathogenesis of Parkinson's disease (PD), but the mechanisms involved in the control of this stress in dopaminergic cells are not fully understood. There is increasing evidence that selenoproteins play a central role in the control of redox homeostasis and cell defense, but the precise contribution of members of this family of proteins during the course of neurodegenerative diseases is still elusive.\", 'We demonstrated first that selenoprotein T (SelT) whose gene disruption is lethal during embryogenesis, exerts a potent oxidoreductase activity. In the SH-SY5Y cell model of dopaminergic neurons, both silencing and overexpression of SelT affected oxidative stress and cell survival. Treatment with PD-inducing neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone triggered SelT expression in the nigrostriatal pathway of wild-type mice, but provoked rapid and severe parkinsonian-like motor defects in conditional brain SelT-deficient mice. This motor impairment was associated with marked oxidative stress and neurodegeneration and decreased tyrosine hydroxylase activity and dopamine levels in the nigrostriatal system. Finally, in PD patients, we report that SelT is tremendously increased in the caudate putamen tissue.', 'These results reveal the activity of a novel selenoprotein enzyme that protects dopaminergic neurons against oxidative stress and prevents early and severe movement impairment in animal models of PD.",
            "output": [
                "Does selenoprotein T exert an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson 's Disease?"
            ]
        },
        {
            "id": "task847-a8cec9fc121a48ec9c393a836521765b",
            "input": "To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume.', 'We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen \u00d7 plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used.', 'Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 \u00b1 0.91 vs 1.15 \u00b1 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 \u00b1 0.084 vs 0.115 \u00b1 0.071 \u03bcg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046).",
            "output": [
                "Is prostate-specific antigen lowering effect of metabolic syndrome influenced by prostate volume?"
            ]
        },
        {
            "id": "task847-b084379855a9452a93688c614c56892f",
            "input": "Polyalthia cerasoides is a medicinal plant known for its ethnopharmacological importance. Despite this, investigation related to its therapeutic benefit is still unexplored.', 'To evaluate the stem bark extracts of Polyalthia cerasoides for pharmacological activities relating to inflammation, nociception and oxidative stress using in vivo and in vitro models.', 'Pet ether, ethyl acetate and chloroform fractions of the stem bark were evaluated for anti-inflammatory activity by carrageenan-induced hind paw edema in rats. Anti-nociceptive activity in mice was assessed using thermally and chemically induced analgesic models. The free radical quenching potential of the extracts was initially analyzed using the in vitro DPPH photometric assay, Hydroxyl radical scavenging and Lipid Peroxidation assays. Then modulatory effect of the extracts on in vivo antioxidant system was evaluated by carbon tetrachloride induced hepatotoxicity and subsequent measurements of antioxidant enzymes such as Superoxide dismutase, Catalase and Peroxidase from the liver homogenate.', 'Among the tested fractions, ethyl acetate extract had substantially inhibited the inflammation by 68.5% that was induced by subcutaneous carrageenan injection whereas pet ether and chloroform extract showed only minimal inhibitory effect. Investigation of the anti-nociceptive activity revealed that the ethyl acetate fractions had significantly repressed the algesia in both the analgesic experimental models. In vitro and in vivo individual antioxidant assays demonstrated that the ethyl acetate fraction has strong free radical quenching potential which also restores the endogenous hepatic enzymes.",
            "output": [
                "Do therapeutic potential of Polyalthia cerasoides stem bark extracts against oxidative stress and nociception?"
            ]
        },
        {
            "id": "task847-773265bd96eb40209513fe5468254611",
            "input": "Previous studies have demonstrated that the administration of antibiotics to patients before performing diagnostic testing for periprosthetic joint infection (PJI) can interfere with the accuracy of test results. Although a single-institution study has suggested that alpha-defensin maintains its concentration and sensitivity even after antibiotic treatment, this has not yet been demonstrated in a larger multiinstitutional study.', '(1) For the evaluation of PJI, is prior antibiotic administration associated with decreased alpha-defensin levels? (2) When prior antibiotics are given, is alpha-defensin a better screening test for PJI than the traditional tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], fluid white blood cells, fluid polymorphonuclear cells [PMNs], and fluid culture)?', \"This retrospective study included data from 106 hip and knee arthroplasties with Musculoskeletal Infection Society-defined PJI from four centers. Of the 106 patients in this study, 30\\xa0(28%) were treated with antibiotics for PJI before diagnostic workup (ABX group), and 76\\xa0(72%) were not treated before the diagnostic workup (NO-ABX group). There were no differences in age, sex, joint, culture-negative rate, or bacteriology between groups. The patients in the ABX group had antibiotics initiated by physicians who commenced care before assessment for PJI by the treating surgeon's service. We compared the alpha-defensin levels and sensitivity between the ABX and NO-ABX groups. Additionally, the sensitivity of the alpha-defensin test was compared to that of traditional tests for PJI among patients on antibiotics.\", 'The administration of antibiotics before performing the alpha-defensin test for PJI was not associated with a decreased median alpha-defensin level (ABX group, median 4.2 [range, 1.79-12.8 S/CO] versus NO-ABX, median 4.9 [range, 0.5-16.8 S/CO], difference of medians: 0.68 S/CO [95% confidence interval {CI}, -0.98 to 1.26], p = 0.451). Furthermore, the alpha-defensin test had a higher sensitivity (100%; 95% CI, 88.4%-100.0%) in diagnosing PJI among patients on antibiotics when compared with the ESR (69.0% [95% CI, 49.17%-84.72%], p = 0.001), the CRP (79.3% [95% CI, 60.3%-92.0%], p = 0.009), the fluid PMN% (79.3% [95% CI, 60.3%-92.0%), p = 0.009), and fluid culture (70.0% [95% CI, 50.6%-85.3%], p = 0.001).",
            "output": [
                "Is the Alpha-defensin Test for Periprosthetic Joint Infections Affected by Prior Antibiotic Administration?"
            ]
        },
        {
            "id": "task847-5d2b11e7250e4a3d89a24f5649cbd3b0",
            "input": "Anhedonia is a significant clinical problem in post-traumatic stress disorder (PTSD). PTSD patients show reduced motivational approach behavior, which may underlie anhedonic symptoms. Oxytocin administration is known to increase reward sensitivity and approach behavior. We therefore investigated whether oxytocin administration affected neural responses during motivational processing in PTSD patients and trauma-exposed controls.', '35 police officers with PTSD (21 males) and 37 trauma-exposed police officers without PTSD (19 males) were included in a within-subjects, randomized, placebo-controlled fMRI study. Neural responses during anticipation of monetary reward and loss were investigated with a monetary incentive delay task (MID) after placebo and oxytocin (40 IU) administration.', 'Oxytocin increased neural responses during reward and loss anticipation in PTSD patients and controls in the striatum, dorsal anterior cingulate cortex and insula, key regions in the reward pathway. Although PTSD patients did not differ from controls in motivational processing under placebo, anhedonia severity in PTSD patients was negatively related to reward responsiveness in the ventral striatum. Furthermore, oxytocin effects on reward processing in the ventral striatum were positively associated with anhedonia.",
            "output": [
                "Does intranasal oxytocin enhance neural processing of monetary reward and loss in post-traumatic stress disorder and traumatized controls?"
            ]
        },
        {
            "id": "task847-aae7a705bbb646f588f6e9dc0ceff701",
            "input": "The aim of the current study was to characterize \u03b2-cell function, insulin sensitivity and line of inheritance in patients with recent-onset type 2 diabetes of Yemenite and non-Yemenite Jewish origin.', 'A cohort study including 121 GAD negative diabetic patients, 59 of Yemenite and 62 of non-Yemenite origin, treated by diet\\xa0\u00b1\\xa0oral antihyperglycemic monotherapy who underwent 180-min meal tolerance test (MMT). Based on MMT, indexes of insulin resistance and secretion were calculated.', 'There were no significant differences in age, sex, diabetes duration, BMI, HbA1c and lipid profile. A significant difference was found in family history of diabetes: 63\\xa0% of patients of Yemenite origin had maternal inheritance versus 35\\xa0% in the non-Yemenite origin (p\\xa0<\\xa00.001). Both indexes of \u03b2-cell function, the insulinogenic and the disposition indexes were significantly lower in patients of Yemenite origin compared with non-Yemenite origin (0.66\\xa0\u00b1\\xa00.4 vs. 0.93\\xa0\u00b1\\xa00.8, p\\xa0=\\xa00.04; 2.3\\xa0\u00b1\\xa01.8 vs. 3.3\\xa0\u00b1\\xa03.3, p\\xa0=\\xa00.04, respectively) with no difference in insulin sensitivity. When females and males were analyzed separately, the difference in maternal inheritance remained significant in both, but the difference in \u03b2-cell function indexes was observed only in males (p\\xa0=\\xa00.03, p\\xa0=\\xa00.01, respectively).",
            "output": [
                "Does early beta-cell dysfunction characterize males with type 2 diabetes of Yemenite origin?"
            ]
        },
        {
            "id": "task847-a8b491b3265f4a22a01fe4555ab1e375",
            "input": "Treatment of implant-associated osteomyelitis regularly involves the use of systemic antibiotics in addition to surgical intervention. However, it remains unclear if perioperative systemic application of bactericide substances can improve overall outcome in models of severe intramedullary infection. The present study investigated the use of systemic gentamicin in addition to a controlled local release from a highly lipophilic gentamicinpalmitate compound while the previous study showed efficacy of sole antibiotic implant-coating.', 'Forty male Sprague-Dawley rats were divided into two groups receiving an intramedullary femoral injection of 10(2) CFU of a common methicillin susceptible Staphylococcus aureus strain (MSSA Rosenbach). Group I received an uncoated implant whereas group II received a coated implant. All animals received a single shot intraperitoneal application of gentamicinsulfate directly after wound closure while the historical control group III (n\\xa0=\\xa020) had no antibiotic treatment at all. Animals were observed for 28 and 42\\xa0days. Serum haptoglobin and relative weight gain were assessed as well as roll over cultures of explanted femur nails and histological scores of periprosthetic infection in dissected femora.', 'Systemic application of gentamicin combined with antibiotic-coated implant did not further reduce bacterial growth significantly compared with systemic or local antibiotic application alone. Combined local and systemic therapy reduced serum haptoglobin significantly after day 7, 28 and 42 whereas systemic application alone did not compare to controls.",
            "output": [
                "Does systemic antibiotic therapy significantly improve outcome in a rat model of implant-associated osteomyelitis induced by Methicillin susceptible Staphylococcus aureus?"
            ]
        },
        {
            "id": "task847-d8824c164d57446abd94850deedd55ba",
            "input": "To investigate the lamina cribrosa (LC) depth and its relationship with the cup-to-disc ratio (CDR) in the eyes with generalized increased optic disc cupping and CDR asymmetry.', 'Glaucoma suspect subjects with a CDR\u22650.7, CDR asymmetry \u22650.2 in the absence of visual field (VF) loss, and normal control subjects were enrolled. The optic nerve head was imaged using the enhanced depth imaging modes of Spectralis optical coherence tomography. The LC depth was determined at the mid-horizontal, and the superior and inferior mid-peripheral regions of the optic nerve head.', 'Disc area and CDRs were larger in the glaucoma suspect group compared with the control group (P<0.001). The mean LC depth was significantly greater in the disc area-matched glaucoma suspect group compared with the normal control group (P<0.001). The mean LC depth was positively correlated with the average and vertical CDRs (r=0.755 and 0.664, respectively; both P<0.001), which was maintained after controlling for the disc area (r=0.756 and 0.645, respectively; both P<0.001). In eyes with CDR asymmetry, the LC was located more posteriorly in eyes with a higher CDR compared with fellow eyes with a lower CDR (P<0.001).",
            "output": [
                "Is lamina Cribrosa Depth Associated With the Cup-to-Disc Ratio in Eyes With Large Optic Disc Cupping and Cup-to-Disc Ratio Asymmetry?"
            ]
        },
        {
            "id": "task847-bf5ebe14179140ba8fa5cd59bb6c4f63",
            "input": "To compare histologically the thickness of conjunctival specimens of normal tension glaucoma (NTG) patients with primary open-angle glaucoma (POAG) patients.', 'In this prospective study, 54 patients scheduled for trabeculectomy were categorized into NTG and POAG based on their maximum untreated intraocular pressure at any time (IOPmax) as measured by Goldmann applanation tonometry. Sixteen patients with NTG (IOPmax\u226421 mm Hg) and 36 patients with high tension POAG (IOPmax>21 mm Hg) were included in the study. Biopsies were taken from the superior bulbar conjunctiva during trabeculectomy. The specimens were fixed in formalin, embedded in methacrylate, histologically sectioned, stained with toluidine blue, and analyzed with a light microscope. The stromal conjunctival thickness (CT) was measured in a standardized way and compared between the 2 groups. Intergroup comparisons were performed using the Mann-Whitney U test for continuous variables and the Fisher exact test for categorical variables. The correlation between the central cornea thickness (CCT) and the CT was investigated by the Spearman test.', 'The stromal CT was significantly thinner in NTG compared with POAG (64\u00b131 vs. 103\u00b144 \u00b5m, respectively; P=0.002). Stromal CT of the whole group was positively correlated with IOPmax (r=0.41; P=0.002; 95% confidence interval, 0.15-0.62) but not with central cornea thickness (r=-0.005; P=0.97; 95% confidence interval, -0.28 to 0.27).",
            "output": [
                "Is the Conjunctiva in Normal Tension Glaucoma Patients Thinner Than in Primary Open-Angle Glaucoma Patients : A Comparative Histologic Study?"
            ]
        },
        {
            "id": "task847-19c8027347f54b17a1b59282a896ad5e",
            "input": "Inflammation plays a major role in the development and progression of atherosclerosis and coronary artery disease (CAD). Inflammation markers, including white blood cell (WBC) count, C-reactive protein (CRP) and interleukin-6 (IL-6), are widely used for cardiovascular risk prediction. The aim of the study was to establish factors associated with WBC, CRP and IL-6 in patients with CAD. Two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism were analyzed (C34T AMPD1, G22A ADA).', 'Plasma concentrations of IL-6 were measured using high-sensitivity ELISA kits, and the nephelometric method was used for high-sensitivity CRP (hs-CRP) measurement in 167 CAD patients.', 'Presence of metabolic syndrome (MS) and its components, presence of heart failure, severity of CAD symptoms, severe past ventricular arrhythmia (sustained ventricular tachycardia [sVT] or ventricular fibrillation [VF]), lower left ventricle ejection fraction, higher left ventricle mass index, higher end-diastolic volume and higher number of smoking pack-years were significantly associated with higher WBC, CRP and IL-6. Strong associations with arrhythmia were observed for IL-6 (median 3.90 vs 1.89 pg/mL, p<0.00001) and CRP concentration (6.32 vs 1.47 mg/L, p=0.00009), while MS was associated most strongly with IL-6. CRP and IL-6 were independent markers discriminating patients with sVT or VF. There were no associations between AMPD1 or ADA genotypes and inflammation markers.",
            "output": [
                "Are inflammation markers associated with metabolic syndrome and ventricular arrhythmia in patients with coronary artery disease?"
            ]
        },
        {
            "id": "task847-fd7f444912ea4ca89f8e42e2121ecc0d",
            "input": "Superficial siderosis is a rare disease that results from chronic bleeding in the subarachnoid space. Haemosiderin deposits throughout the subpial layers of the brain and spinal cord lead to progressive sensorineural hearing loss, which is seen in 95 per cent of patients with superficial siderosis. The impact of cochlear implantation on the quality of life of superficial siderosis patients is under debate.', 'A 38-year-old male with superficial siderosis presented with bilateral progressive sensorineural hearing loss. The patient underwent cochlear implantation and his quality of life was improved as evaluated by the Abbreviated Profile of Hearing Aid Benefit inventory.",
            "output": [
                "Is cochlear implantation a therapeutic option for superficial siderosis patients with sensorineural hearing loss?"
            ]
        },
        {
            "id": "task847-2dc998f4358b41e4893bbf2ec5e61f14",
            "input": "Several factors influence the outcome after acute ischemic stroke secondary to proximal occlusions of cerebral vessels. Among others, noneligibility for intravenous thrombolysis (IVT) and incomplete revascularization have been identified as predictors of unfavorable outcome. The aim of this study was to investigate whether concomitant IVT influences the revascularization efficacy in mechanical thrombectomy (MT).', 'This study conducted a retrospective analysis of all consecutive patients presenting with an anterior circulation stroke due to large-artery occlusion with imaging evidence who were treated with MT between July 2012 and December 2013 at 2 high-volume stroke centers. Imaging data were regraded and re-evaluated according to the modified Treatment in Cerebral Ischemia scale and its respective vessel occlusion site definitions. Clinical end points included National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale; imaging and procedural measures were technical end points.', 'We identified 93 patients who presented with an occlusion of the middle cerebral artery (MCA): of these patients, 66 (71%) received IVT. We did not find statistically significant differences in the baseline NIHSS score, time from symptom onset to groin puncture, and age when comparing the IVT group with the non-IVT group. The rate of successful recanalizations (modified Treatment in Cerebral Ischemia score\\u2009\u2265\\u20092b) was significantly higher in patients with MCA occlusion and concomitant IVT (P\\u2009=\\u2009.01). Stepwise logistic regression identified IVT and thrombus length as predictive factors for successful mechanical recanalization (P\\u2009=\\u2009.004, P\\u2009=\\u2009.002).",
            "output": [
                "Does intravenous Thrombolysis facilitate Successful Recanalization with Stent-Retriever Mechanical Thrombectomy in Middle Cerebral Artery Occlusions?"
            ]
        },
        {
            "id": "task847-e5f84cbaa78a44da90b6b982e379d9c2",
            "input": "Internal carotid artery (ICA) stenosis can lead to cerebral hypoperfusion and is a common cause of stroke. As susceptibility weighted imaging (SWI) has been used for penumbra imaging in acute ischemic stroke, we aimed at analyzing hypoperfusion using SWI in patients with ICA stenosis.', 'Clinical characteristics, asymmetric cortical vessel sign (more and/or larger, hypointense asymmetric cortical vessels) on SWI, Doppler sonography results and diffusion weighted imaging (DWI) lesion volume were retrospectively analyzed in patients with ICA stenosis. In a subgroup of patients, volume of prolonged time to peak and volume of prolonged time to peak of the residue curve (Tmax) were measured as reference standard. Outcome was assessed as modified Rankin score at discharge.', '104 patients were included. Median age was 72 and median degree of stenosis 70% according to NASCET. 13% had a asymmetric cortical vessel sign. These patients had a higher degree of stenosis (80% vs. 70%, p=0.004), were more often symptomatic (93% vs. 61%, p=0.020) and had higher DWI volume (7.3ml vs. 0.2ml, p=0.011). Specificity for the prediction of DWI lesions was 86%. Also, patients with asymmetric cortical vessel sign had lower rates of favorable outcome (mRS=0-2; 57% vs. 82%, p=0.033) and volumes of Tmax\u22654s, \u22656s, \u22658s, \u226510s and TTP\u22652s, \u22654s, \u22656s were significantly higher. In multivariate analysis, asymmetric cortical vessel sign was an independent negative predictor of favorable outcome (mRS 0-2; OR 0.184; CI [0.039; 0.875] p=0.033).",
            "output": [
                "Does cortical vessel sign on susceptibility weighted imaging reveal clinically relevant hypoperfusion in internal carotid artery stenosis?"
            ]
        },
        {
            "id": "task847-b5f4b014985944149d6fc4d22103ec7f",
            "input": "To explore stakeholder views on cell-free DNA testing and highlight findings important for successful implementation and the provision of best practice in counseling.', 'Noninvasive tests based on the analysis of cell-free fetal DNA are now widely available in clinical practice and applications are expanding rapidly. It is essential that stakeholder views are considered in order to identify and address any ethical and social issues. We provide an overview of stakeholder viewpoints and then focus on the key issues of informed decision making, test uptake, service delivery and information sources.",
            "output": [
                "Does stakeholder attitudes and need regarding cell-free fetal DNA testing?"
            ]
        },
        {
            "id": "task847-f1fadd4d67664e2c96b1713912536e17",
            "input": "Hypothermia has been shown to be neuroprotective in the therapy of ischemic stroke in the brain. To date no studies exist on the level of the inner retina and it is unclear if hypothermia would prolong the ischemic tolerance time of retinal ganglion cells, which are decisive in many ischemic retinopathies.', 'Bovine eyes were enucleated and stored either at 21\u00b0C or 37\u00b0C for 100 or 340 minutes, respectively. Afterwards the globes were dissected, the retina was prepared and either the spontaneous ganglion cell responses were measured or the retina was incubated as an organotypic culture for additional 24 hours. After incubation the retina was either processed for histology (H&E and DAPI staining) or real-time PCR (Thy-1 expression) was performed.', 'Hypothermia prolonged ganglion cell survival up to 340 minutes under ischemic conditions. In contrast to eyes kept at 37\u00b0C the eyes stored at 21\u00b0C still showed spontaneous ganglion cell spiking (56.8% versus 0%), a 5.8 fold higher Thy-1 mRNA expression (not significant, but a trend) and a preserved retinal structure after 340 minutes of ischemia.",
            "output": [
                "Does hypothermia protect and Prolongs the Tolerance Time of Retinal Ganglion Cells against Ischemia?"
            ]
        },
        {
            "id": "task847-e5b8005bb21a430db4eb746a9ac333fc",
            "input": "Little is known regarding the incidence rate of and factors associated with developing chronic kidney disease after continuous renal replacement therapy (CRRT) in acute kidney injury (AKI) patients. We investigated renal outcomes and the factors associated with incomplete renal recovery in AKI patients who received CRRT.', 'Between January 2011 and November 2013, 408 patients received CRRT in our intensive care unit. Of them, patients who had normal renal function before AKI and were discharged without maintenance renal replacement therapy (RRT) were included in this study. We examined the incidence of incomplete renal recovery with an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) and factors that increased the risk of incomplete renal recovery after AKI.', 'In total, 56 AKI patients were discharged without further RRT and were followed for a mean of 8 months. Incomplete recovery of renal function was observed in 20 of the patients (35.7%). Multivariate analysis revealed old age and long duration of anuria as independent risk factors for incomplete renal recovery (odds ratio [OR], 1.231; 95% confidence interval [CI], 1.041 to 1.457; p = 0.015 and OR, 1.064; 95% CI, 1.001 to 1.131; p = 0.047, respectively). In a receiver operating characteristic curve analysis, a cut-off anuria duration of 24 hours could predict incomplete renal recovery after AKI with a sensitivity of 85.0% and a specificity of 66.7%.",
            "output": [
                "Does duration of anuria predict recovery of renal function after acute kidney injury requiring continuous renal replacement therapy?"
            ]
        },
        {
            "id": "task847-68f186a3f5b44738b57e60558bfa1012",
            "input": "5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been used for the treatment of skin photoaging. It can significantly improve the appearance of fine lines, dotted pigmentation, and roughness of photoaged skin. However, the mechanisms by which ALA-PDT yields rejuvenating effects on photoaged skin have not been well elucidated. Thus, in this study we explored the effects of ALA-PDT in photoaged fibroblasts.', 'We established a stress-induced premature senescence (SIPS) model by repeated exposures of human dermal fibroblasts (HDFs) to ultraviolet B (UVB) irradiation. Cells were irradiated by red light laser at 635nm wavelength (50mW/cm(2)). Intracellular protoporphyrin IX (PpIX) was detected by confocal microscopy. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) change were detected by fluorescence microscopy and flow cytometry. Morphological changes were observed by optical microscopy. Proliferative activity was measured by a cell counting kit-8 (CCK-8). Cell apoptosis was detected by fluorescence microscopy using Hoechst staining and flow cytometry using annexin V/propidium Iodide double staining.', 'Intracellular PpIX fluorescence in UVB-induced premature senescent HDFs (UVB-SIPS-HDFs) reached the highest intensity after incubation with 1.00mmol/L ALA for 6h (P<0.05). Compared with control group, intracellular ROS level, MMP, and apoptotic rate were increased (P<0.05) and proliferative activity was decreased (P<0.05) in UVB-SIPS-HDFs treated with ALA-PDT, which were positively correlated to ALA incubation time and red light laser dose.",
            "output": [
                "Does aLA-PDT elicit oxidative damage and apoptosis in UVB-induced premature senescence of human skin fibroblasts?"
            ]
        },
        {
            "id": "task847-1a63f63da28f49d5a1a1fa14cd5e0399",
            "input": "This magnetic resonance imaging (MRI) study of 26 subjects with nasal congestion was performed to assess in the complete nasal passage both the anatomical effect of the marketed Breathe Right Nasal Strip (BRNS) relative to placebo and the potential adjunctive effect of using a decongestant in combination with the BRNS.', 'Randomized, crossover study.', 'The study consisted of two parts, the first involving application of either the BRNS or the placebo strip in a randomized, crossover design with evaluator blinding, and repeated MRI scanning; and the second a sequential process of decongestant administration, MRI scanning, application of the BRNS, and repeated MRI. The same anatomical MRI protocol was used throughout. Nasal patency was assessed in the whole nasal passage and eight subregions (by inferior-superior, anterior-posterior division). Numerical response scores representing subjective nasal congestion were also obtained.', 'Results demonstrate significant anatomical enlargement with the BRNS relative to placebo (P < .001), as well as an additive effect of using a decongestant in combination with the BRNS; both supported by a strong and significant negative correlation with the subjective nasal response measures of nasal congestion (r = -0.98, P = .002). Furthermore, analysis of the nasal subregions indicates that this adjunctive effect arises from a partially localized action of the complementary products: the BRNS acting primarily anteriorly in the nose and the decongestant mainly posteriorly.",
            "output": [
                "Does magnetic resonance imaging reveal the complementary effects of decongestant and Breathe Right Nasal Strips on internal nasal anatomy?"
            ]
        },
        {
            "id": "task847-41b33296feed4691b53898640d25e1da",
            "input": "Obesity and the metabolic syndrome occur in approximately one-third of patients with alcoholic liver disease (ALD). The increased consumption of fructose parallels the increased prevalence of obesity and the metabolic syndrome in the United States and worldwide. In this study, we investigated whether dietary high fructose potentiates chronic alcohol-induced liver injury, and explored potential mechanism(s).', 'Six-week-old male C57BL/6J mice were assigned to 4 groups: control, high fructose, chronic ethanol (EtOH), and high fructose plus chronic alcohol. The mice were fed either control diet or high-fructose diet (60%, w/w) for 18\\xa0weeks. Chronic alcohol-fed mice were given 20% (v/v) ethanol (Meadows-Cook model) ad\\xa0libitum as the only available liquid from the 9th week through the 18th week. Liver injury, steatosis, hepatic inflammatory gene expression, and copper status were assessed.', 'High-fructose diet and chronic alcohol consumption alone each induce hepatic fat accumulation and impair copper status. However, the combination of dietary high fructose plus chronic alcohol synergistically induced liver injury as evidenced by robustly increased plasma alanine aminotransferase and aspartate aminotransferase, but the combination did not exacerbate hepatic fat accumulation nor worsen copper status. Moreover, FE-fed mice were characterized by prominent microvesicular steatosis. High-fructose diet and chronic alcohol ingestion together led to a significant up-regulation of Kupffer cell (KC) M1 phenotype gene expression (e.g., tumor necrosis factor-\u03b1 and monocyte chemoattractant protein-1), as well as Toll-like receptor 4 (TLR4) signaling gene expression, which is also associated with the up-regulation of KCs and activation marker gene expression, including Emr1, CD68, and CD163.",
            "output": [
                "Does chronic Alcohol Consumption cause Liver Injury in High-Fructose-Fed Male Mice Through Enhanced Hepatic Inflammatory Response?"
            ]
        },
        {
            "id": "task847-b602137588424e21ae574159fe04d56f",
            "input": "Serum levels of apolipoprotein E (apoE) have been suggested as potential biomarker for dementia, but the long-term association between apoE and risk of dementia is uncertain.', \"Between 1990 and 1993, we measured serum apoE by immunoassay in 1042 non-demented individuals (mean \u00b1 SD age 68.4 \u00b1 7.3 years; 59.3% women) from the population-based Rotterdam Study. Follow-up for dementia was complete until 2014. We used Cox models to determine the risk of dementia and Alzheimer's disease in relation to apoE, adjusting for age, sex, educational level, cardiovascular risk factors, and additionally APOE genotype.\", \"Serum apoE was associated to APOE genotype (p-trend=1.0E-51, r(2)=0.21). In men, apoE tended to be lower with age, whereas in women the opposite was observed (p-trend=0.07 and 0.08, respectively). During a median follow-up of 15.7 years (IQR 9.7-21.7), 220 participants developed dementia, of whom 180 had Alzheimer's disease. Lower serum apoE was associated with an increased risk of dementia (HR, 95%CI, per SD decrease: 1.25, 1.05-1.48) and in particular Alzheimer's disease (1.51, 1.23-1.86), which remained statistically significant for Alzheimer's disease after additionally adjusting for APOE genotype (1.28, 1.01-1.62). When stratifying analyses in 5-year time frames, risk estimates were similar throughout the study period. Serum apoE tended to marginally improve 20-year prediction of Alzheimer's disease (IDI 0.008, 95%CI -0.001-0.026, p=0.086), but not all dementia.",
            "output": [
                "Is serum apolipoprotein E associated with long-term risk of Alzheimer 's disease : The Rotterdam Study?"
            ]
        },
        {
            "id": "task847-e98f226c48044b39839d4576f10a94ec",
            "input": "Elevated H2O2 levels are associated with inflammatory diseases and H2O2 exposure is known to disrupt epithelial barrier function, leading to increased permeability and decreased electrical resistance. In normal human bronchial epithelial (NHBE) cells, fully differentiated at the air liquid interface (ALI), H2O2 activates an autocrine prostaglandin pathway that stimulates transmembrane adenylyl cyclase (tmAC) as well as soluble adenylyl cyclase (sAC), but the role of this autocrine pathway in H2O2-mediated barrier disruption is not entirely clear.', 'To further characterize the mechanism of H2O2-induced barrier disruption, NHBE cultures were treated with H2O2 and evaluated for changes in transepithelial resistance and mannitol permeability using agonist and inhibitors to dissect the pathway.', 'A short (<10 min) H2O2 treatment was sufficient to induce resistance and permeability changes that occurred 40 min to 1 h later and the changes were partially sensitive to EP1 but not EP4 receptor antagonists. EP1 receptors were localized to the apical compartment of NHBE. Resistance and permeability changes were sensitive to inhibition of sAC but not tmAC and were partially blocked by PKA inhibition. Pretreatment with a PLC inhibitor or an IP3 receptor antagonist reduced changes in resistance and permeability suggesting activation of sAC occurred through increased intracellular calcium.",
            "output": [
                "Does soluble adenylyl cyclase mediate hydrogen peroxide-induced changes in epithelial barrier function?"
            ]
        },
        {
            "id": "task847-f0faa4069284429e898cff8d5d2de410",
            "input": "Stroke unit care is associated with decrease in mortality and improvement in neurological outcome in patients with acute stroke. Heart rate is a commonly monitored variable in the stroke unit. However, little is known about tachycardia burden in the stroke unit and its association with outcome.', 'To investigate the effects of tachycardia burden in the stroke unit on functional outcome in patients with acute ischemic stroke.', 'We collected data from 246 patients with acute ischemic stroke admitted to our stroke unit between July 2013 and June 2014. Tachycardia burden was defined as duration of heart rate over 95 per minute divided by the total monitoring time, using the heart rate data sampled every 1 min. We divided the study population into quartiles of tachycardia burden and analyzed their association with poor three-month functional outcome (modified Rankin Scale score of \u22653).', 'Among included patients (age, 67.4 \u00b1 12.8; male, 53.7%), tachycardia burden was 0.7% (median, interquartile range [0.1-5.7%]). The patients with higher tachycardia burdens were older, more likely to have higher stroke severity, cardioembolic etiology, atrial fibrillation, fever, pneumonia, higher initial glucose level, and higher white blood cell count. As compared with the lowest quartile (<0.1%), the highest quartile of tachycardia burden (\u22656.0%) was significantly associated with poor outcome (adjusted odds ratio, 5.10; 95% confidence interval, 1.38-18.90; p = 0.01) after adjustment for covariates.",
            "output": [
                "Is tachycardia burden in stroke unit associated with functional outcome after ischemic stroke?"
            ]
        },
        {
            "id": "task847-fa71cee85c5645ca9b8a38be43b10ef7",
            "input": "To investigate the effects of non-drug interventions on the sleep quality of patients after mechanical cardiac valve implantation.', 'In this prospective, randomized, controlled trial, 64 patients scheduled for mechanical mitral valve replacement were recruited. Patients underwent cognitive behavioral therapy and wore noise cancelling earplugs and eye mask. Sleep quality was evaluated on the 4th after admission and the 5th days after operation. The primary outcome was the total sleep quality score differences between the 4th day after admission and the 5th day after operation.', 'All patients had been suffering from poor sleep quality for a month before admission. There was no difference between both groups on the 4th day after admission. Overall sleep quality in the intervention group was better than in the control group on the 5th day after operation. The subjective sleep quality of the patients in each group was significantly lower on the 5th day after the operation than on the 4th day after admission (P <0.05).",
            "output": [
                "Does cardiac Valve Noise Reduction by Non-Drug Interventions improve the Sleep Quality of Patients after Mechanical Cardiac Valve Implantation?"
            ]
        },
        {
            "id": "task847-9c1a2bb129d04fe5bc78d310b87f654b",
            "input": "To examine the effects of an experiential learning model of ultrasound training on preclinical medical students' knowledge and practice of Focused Assessment with Sonography for Trauma (FAST) examination.\", \"The study was conducted in 2 phases. In phase 1, first- and second-year medical students participated in a 45-minute didactic presentation and subsequent 1-hour hands-on practice followed by 3-5 precepted FAST examinations in the emergency department. A pretest or posttest design was used to examine the participants' knowledge interpreting ultrasound images of the FAST examination. In phase 2, students performed FAST scans on patients with abdominal complaints under the supervision of emergency ultrasound faculty over a 1-year period. The participants were scored based on window acquisition, quality of images, accuracy of FAST scan interpretation, confidence level rated by participant, and supervising attending physician.\", 'In phase 1, 68 novice medical students participated in 11 training sessions offered over a 1-year period. Students showed significant improvement in basic ultrasound and abdominal anatomy knowledge. The mean score improved from a pretest score of 5.8 of 10 (95% CI: 5.3-6.2) to a posttest score of 7.3 of 10 (95% CI: 7-7.6). The students also demonstrated a significant improvement in FAST image interpretation (pretest of 6.2 [95% CI: 5.9-6.6] and posttest of 7.6 [95% CI: 7.1-7.9]). In phase 2, 22 students performed 304 FAST examinations on patients. At the beginning of their training when they performed less than 10 FAST scans, students were able to complete the right upper quadrant view in 88.9%, left upper quadrant view in 69.7%, subxiphoid in 64.7%, and pelvic view in 70% of scans. Across all views of the FAST examination, increasing level of practice was associated with improvement in successfully completing the examination. The absolute increase in the proportion experiencing success in the right upper quadrant view was 1.6%, 3.6%, and 6.2% for the 10-19, 20-29, and >30 groups, respectively, of which none were statistically significant. However, the improvements in the left upper quadrant view was 12.7%, 11.6%, 15.7% for the 10-19, 20-29, and >30 groups, respectively. In all views, performing >30 examinations more than doubled the odds of successfully completing the examination.",
            "output": [
                "Does an Experiential Learning Model facilitate Learning of Bedside Ultrasound by Preclinical Medical Students?"
            ]
        },
        {
            "id": "task847-3c565dc895cf4fdb9e82180a477240da",
            "input": "The mechanism through which oxygenated hypothermic machine perfusion (HMP) improves viability of human extended criteria donor (ECD) livers is not well known. Aim of this study was to examine the benefits of oxygenated HMP after static cold storage (SCS).', 'Eighteen ECD livers that were declined for transplantation underwent ex situ viability testing using normothermic (37 \u00b0C) machine perfusion (NMP) after traditional SCS (0 \u00b0C-4 \u00b0C) for 7 to 9 hours. In the intervention group (n = 6), livers underwent 2 hours of oxygenated HMP (at 12 \u00b0C) after SCS and before NMP. Twelve control livers underwent NMP without oxygenated HMP after SCS.', 'During HMP, hepatic ATP content increased greater than 15-fold, and levels remained significantly higher during the first 4 hours of NMP in the HMP group, compared with controls. Cumulative bile production and biliary secretion of bilirubin and bicarbonate were significantly higher after HMP, compared with controls. In addition, the levels of lactate and glucose were less elevated after HMP compared with SCS preservation alone. In contrast, there were no differences in levels of hepatobiliary injury markers AST, ALT, LDH, and gamma-GT after 6 hours of NMP. Hepatic histology at baseline and after 6 hours of NMP revealed no differences in the amount of ischemic necrosis between both groups.",
            "output": [
                "Does oxygenated Hypothermic Machine Perfusion After Static Cold Storage improve Hepatobiliary Function of Extended Criteria Donor Livers?"
            ]
        },
        {
            "id": "task847-cf264ddd9e8a43f2b542f194a82e4e95",
            "input": "Cardiometabolic disorders are rapidly becoming major public health challenges. Valproic acid (VPA) is a widely prescribed anticonvulsant drug.', 'We hypothesized that treatment with VPA would improve the regulation of glucose and atherogenic dyslipidemia through reduction in circulating corticosterone.', 'Female Wistar rats recieved (p.o.) combined oral contraceptive (COC) containing 1.0\\u2009\u00b5g ethinylestradiol plus 5.0\\u2009\u00b5g levonorgestrel and valproic acid (VPA; 20\\u2009mg) for 8 weeks.', 'Treatment with COC led to elevated fasting blood glucose, insulin, corticosterone, triglycerides (TG), TG/HDL-cholesterol ratio, insulin resistance (IR) and impaired glucose tolerance. VPA significantly attenuated the alterations induced by COC treatment, but did not affect the corticosterone level. However, VPA treatment led to significant increases in plasma insulin, corticosterone, atherogenic lipids and impaired glucose tolerance in rats not treated with COC.",
            "output": [
                "Is improvement of oral contraceptive-induced glucose dysregulation and dyslipidemia by valproic acid independent of circulating corticosterone?"
            ]
        },
        {
            "id": "task847-c633f0292abe429e8714da6be0e75e39",
            "input": "We previously reported omega-3 polyunsaturated fatty acids (n-3PUFAs) supplementation does not reduce atrial fibrillation (AF) following coronary artery bypass graft (CABG) surgery. The aim of the present study is to evaluate the impact of n-3 PUFAs on electrocardiogram (ECG) atrial arrhythmic markers and compare with expression of gap-junction proteins, Connexins.', 'Subset of clinical trial subjects with right atrial sampling during CABG surgery included. Twelve-lead ECG performed at recruitment and at surgery [after supplementation with n-3 PUFA (\u223c1.8 g/day) or matched placebo] for \u223c14 days. Electrocardiograms analysed for maximum P-wave duration (P-max) and difference between P-max and minimum P-wave duration, P-wave dispersion (PWD). Right atrial specimens analysed for expression of Connexins 40 and 43 using real-time quantitative polymerase chain reaction (qPCR) and western blot. Serum levels of n-3 PUFA at baseline, at surgery, and atrial tissue levels at surgery collated from file. Postoperative AF was quantified by analysing data from stored continuous electrograms. A total of 61 patients (n-3 PUFA 34, Placebo 27) had ECG analysis and AF burden, of which 52 patients (26 in each group) had qPCR and 16 (8 in each group) had western blot analyses for Connexins 40 and 43. No difference between the two groups in ECG parameters or expression of Connexin 40 or 43. P-wave dispersion in the preoperative ECG independently predicted occurrence of AF following CABG surgery.",
            "output": [
                "Do omega-3 fatty acids alter P-wave parameters in electrocardiogram or expression of atrial connexins in patients undergoing coronary artery bypass surgery?"
            ]
        },
        {
            "id": "task847-4ea4bf1bcb244a3a9164b023bbf410c4",
            "input": "As HPV-induced cases of oral malignancy increase, it is important to understand the molecular differences between HPV positive and negative head and neck squamous cell carcinoma (HNSCC). PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs aberrantly expressed in cancer. We analyzed global piRNA expression patterns to define the HNSCC piRNA transcriptome and assess whether HPV infection status associates with changes in piRNA levels.', 'A total of 498 HNSCC small RNA sequencing libraries were acquired from the Cancer Genomics Hub (cgHUB) Data Repository and a custom sequence analysis pipeline was developed to deduce piRNA expression from raw sequencing data. Expression matrices were aligned to clinicopathological features in order to analyze piRNA expression patterns across different HNSCC groups. The association of a piRNA signature with HPV-positive patient survival was evaluated using a Cox proportional hazard model.', 'Analysis of piRNA levels between HNSCC and non-malignant tissues revealed distinct expression patterns, with 87 piRNAs exclusively expressed in tumor samples. HPV infection status affected the expression of 41 of these piRNAs. Eleven (26.8%) piRNAs were significantly downregulated in HPV16/18 tumors compared to other HPV types. Remarkably, expression of a combination of five-piRNAs in HPV-positive HNSCC tumors was associated with worse overall survival.",
            "output": [
                "Is hPV status associated with altered PIWI-interacting RNA expression pattern in head and neck cancer?"
            ]
        },
        {
            "id": "task847-f6ec4428092c4b3b9f42a40d8ded0916",
            "input": "To identify whether Pulsatilla saponin A (PsA), an active molecule extracted from Pulsatilla chinensis regel, can induce acute myeloid leukemia (AML) cells differentiate.', 'PsA was isolated from P. chinensis, and its effects of differentiation induction on both AML cell lines and the primary leukemia cells were investigated.', 'Compared with the untreated control, PsA induced the differentiation of U937 cells, K562 cells and HL-60 cells, represented as the increased CD15+ cells in a dose- and time-dependent manner in all the three AML cell lines, after PsA treatment. As the same time, the cell morphology of these AML cells was changed correspondingly; the cytoplasm/nuclei ratio was increased, basophilic cytoplasm was decreased, and eccentric nucleus and granules were also observed. Also, the same effects of differentiation induction by PSA were confirmed in the primary leukemia cells. However, the specific MEK/ERK inhibitor U0126 effectively abrogated the differentiation induced by PsA in vitro.",
            "output": [
                "Does pulsatilla saponin A induce differentiation in acute myeloid leukemia in vitro?"
            ]
        },
        {
            "id": "task847-c52bba3725c44c2daa408536f0b7aa40",
            "input": "To examine the relationships between study quality, author prestige, journal impact factors, and citation rates of trials and to examine whether journal impact factors mediated the relationships between study quality and author prestige on citation rates.', 'We used bibliometric data from 128 controlled trials included in a recent meta-analysis on brief alcohol interventions for adolescents and young adults. We obtained the number of citations from ISI Web of Knowledge and Google Scholar; journal impact factors were obtained from ISI Web of Knowledge. Linear regression models were used to examine the direct and indirect effects of interest.', 'The results indicated that studies were published in journals with higher impact factors when first authors had higher h-indices and studies were funded, but this was largely because those studies were of higher quality. Studies were cited more frequently when first authors had higher h-indices and studies were funded, even after adjusting for study quality proxies. The observed associations between study quality and author prestige on citation rates were also partly mediated through journal impact factors.",
            "output": [
                "Are brief alcohol intervention trials conducted by higher prestige authors and published in higher impact factor journals cited more frequently?"
            ]
        },
        {
            "id": "task847-ecc4f97cc48b4434a8161910772c65bc",
            "input": "To evaluate the effects of an intensive postoperative physiotherapy program focused on respiratory exercises in patients undergoing lobectomy by open thoracotomy.', 'Quasi-experimental study.', 'Tertiary referral academic hospital.', '208 patients undergoing lobectomy by open thoracotomy.', 'Control group patients (n=102) received standard medical/nursing care, and experimental group patients (n=106) added to the standard clinical pathway a daily physiotherapy program focused on respiratory exercises until discharge.', 'Analyzed outcomes were the frequency of postoperative pulmonary complications (PPCs) more amenable to physiotherapy (pneumonia, atelectasis and respiratory insufficiency) and length of hospital stay (LOS).', 'Both groups were comparable regarding preoperative and surgical characteristics. Incidence of PPCs was 20.6% in control and 6.6% in experimental group (P=.003). Median (IQR) LOS in control group was 14 (7) days (Huber M estimator 14.21) and 12 (6) days (Huber M estimator 12.81) in experimental. Logistic regression model identified the evaluated physiotherapy program (P=.017; EXP [B] 95% CI 0.081-0.780) and % FEV1 (P=.042; EXP [B] 95% CI 0.941-0.999) as protective factors for the development of PPCs in patients undergoing lobectomy.",
            "output": [
                "Do postoperative Respiratory Exercises Reduce the Risk of Developing Pulmonary Complications in Patients Undergoing Lobectomy?"
            ]
        },
        {
            "id": "task847-a4f0dfcc6b5448a6a9705ee7a17681f8",
            "input": "Fibroblast growth factor receptors (FGFR) are critical for cell proliferation and differentiation. Mutation and/or translocation of FGFRs lead to aberrant signaling that often results in developmental syndromes or cancer growth. As sequencing of human tumors becomes more frequent, so does the detection of FGFR translocations and fusion proteins. The research conducted in this article examines a frequently identified fusion protein between FGFR3 and transforming acidic coiled-coil containing protein 3 (TACC3), frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Using titanium dioxide-based phosphopeptide enrichment (TiO2)-liquid chromatography (LC)-high mass accuracy tandem mass spectrometry (MS/MS), it was demonstrated that the fused coiled-coil TACC3 domain results in constitutive phosphorylation of key activating FGFR3 tyrosine residues. The presence of the TACC coiled-coil domain leads to increased and altered levels of FGFR3 activation, fusion protein phosphorylation, MAPK pathway activation, nuclear localization, cellular transformation, and IL3-independent proliferation. Introduction of K508R FGFR3 kinase-dead mutation abrogates these effects, except for nuclear localization which is due solely to the TACC3 domain.",
            "output": [
                "Does oncogenic Gene Fusion FGFR3-TACC3 be Regulated by Tyrosine Phosphorylation?"
            ]
        },
        {
            "id": "task847-21bd1084b1344216877c5050dcb9f828",
            "input": "The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression.', 'Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2\\xa0mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies.', 'Immunofluorescent staining revealed TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha-induced TRPA1 responses after Biodentine treatment.",
            "output": [
                "Does biodentine reduce Tumor Necrosis Factor Alpha-induced TRPA1 Expression in Odontoblastlike Cells?"
            ]
        },
        {
            "id": "task847-00fd896444ec40029319e424cdd71497",
            "input": "Reports of locomotive syndrome (LS) have recently been increasing. Although physical performance measures for LS have been well investigated to date, studies including psychiatric assessment are still scarce. Hence, the aim of this study was to investigate both physical and mental parameters in relation to presence and severity of LS using a 25-question geriatric locomotive function scale (GLFS-25) questionnaire.', '150 elderly people aged over 60 years who were members of our physical-fitness center and displayed well-being were enrolled in this study. Firstly, using the previously determined GLFS-25 cutoff value (=16 points), subjects were divided into two groups accordingly: an LS and non-LS group in order to compare each parameter (age, grip strength, timed-up-and-go test (TUG), one-leg standing with eye open, back muscle and leg muscle strength, degree of depression and cognitive impairment) between the groups using the Mann-Whitney U-test followed by multiple logistic regression analysis. Secondly, a multiple linear regression was conducted to determine which variables showed the strongest correlation with severity of LS.', 'We confirmed 110 people for non-LS (73%) and 40 people for LS using the GLFS-25 cutoff value. Comparative analysis between LS and non-LS revealed significant differences in parameters in age, grip strength, TUG, one-leg standing, back muscle strength and degree of depression (p\\xa0<\\xa00.006, after Bonferroni correction). Multiple logistic regression revealed that functional decline in grip strength, TUG and one-leg standing and degree of depression were significantly associated with LS. On the other hand, we observed that the significant contributors towards the GLFS-25 score were TUG and degree of depression in multiple linear regression analysis.",
            "output": [
                "Is locomotive syndrome associated not only with physical capacity but also degree of depression?"
            ]
        },
        {
            "id": "task847-bebf211c28924b5698a413ae95878480",
            "input": "To determine the utility of a prehospital sepsis screening protocol utilizing systemic inflammatory response syndrome (SIRS) criteria and end-tidal carbon dioxide (ETCO2).', 'We conducted a prospective cohort study among sepsis alerts activated by emergency medical services during a 12 month period after the initiation of a new sepsis screening protocol utilizing \u22652 SIRS criteria and ETCO2 levels of \u226425 mmHg in patients with suspected infection. The outcomes of those that met all criteria of the protocol were compared to those that did not. The main outcome was the diagnosis of sepsis and severe sepsis. Secondary outcomes included mortality and in-hospital lactate levels.', 'Of 330 sepsis alerts activated, 183 met all protocol criteria and 147 did not. Sepsis alerts that followed the protocol were more frequently diagnosed with sepsis (78% vs 43%, P < .001) and severe sepsis (47% vs 7%, P < .001), and had a higher mortality (11% vs 5%, P = .036). Low ETCO2 levels were the strongest predictor of sepsis (area under the ROC curve (AUC) of 0.99, 95% CI 0.99-1.00; P < .001), severe sepsis (AUC 0.80, 95% CI 0.73-0.86; P < .001), and mortality (AUC 0.70, 95% CI 0.57-0.83; P = .005) among all prehospital variables. Sepsis alerts that followed the protocol had a sensitivity of 90% (95% CI 81-95%), a specificity of 58% (95% CI 52-65%), and a negative predictive value of 93% (95% CI 87-97%) for severe sepsis. There were significant associations between prehospital ETCO2 and serum bicarbonate levels (r = 0.415, P < .001), anion gap (r = -0.322, P < .001), and lactate (r = -0.394, P < .001).",
            "output": [
                "Does a prehospital screening tool utilizing end-tidal carbon dioxide predict sepsis and severe sepsis?"
            ]
        },
        {
            "id": "task847-8bc3904fd15c493b8f555c9c46c94c21",
            "input": "Body mass index (BMI)-for-age curves have been developed in the USA, but not compared with other populations. This study created gender-specific intrauterine BMI-for-age curves for Italian preterm infants and compared them with the USA version.', 'Data on 92 262 newborn infants, born at 26-42 weeks of gestational age in the north-eastern Italian region of Friuli Venezia Giulia between 2005 and 2013, were analysed to create gender-specific BMI-for-age curves. Gender-specific and age-specific BMI Z scores for Italian infants were calculated using the parameters of the USA growth curves and the World Health Organization charts.', 'Gender-specific BMI-for-age at birth curves were developed for premature Italian infants from 26 gestational weeks. The comparison with the USA charts showed no significant difference in BMI percentiles in Italian infants born at \u226433 gestational weeks, but infants born at \u226534 gestational weeks had a significantly higher BMI than the USA population, by 0.2 standard deviations.",
            "output": [
                "Are body mass index curves for Italian preterm infants comparable with American curves for infants born before 34 weeks of gestational age?"
            ]
        },
        {
            "id": "task847-ecd5f1afa13c4278934cdd34e92ca3f5",
            "input": "As a result of improved diagnostic methods, medical treatment, surgical correction, and palliation in childhood, there is a growing number of adult patients with congenital heart disease (CHD) who may experience heart failure and subsequently require heart transplantation (HT). Because of complex anatomy, previous operations, and frequently increased pulmonary vascular resistance (PVR), these patients represent a group with a higher risk of early mortality after transplantation.', 'From May 1999 to December 2014, our institution performed 25 HTs in adult patients with end-stage CHD. We present our data and outcomes of transplantation in this group.', 'The median age at transplantation was 38\\xa0years (range, 18.4-53.7 years). Survival was 88% at 30 days, 88% at 1 year, and 77% at 5 years. We identified long donor heart ischemic time (>4 hours) as an important risk factor for early mortality. There\\xa0was no significant difference in the survival of\\xa0patients undergoing transplantation for CHD and\\xa0patients undergoing transplantation for other diagnoses.",
            "output": [
                "Does non-Fontan Adult Congenital Heart Disease Transplantation Survival be Equivalent to Acquired Heart Disease Transplantation Survival?"
            ]
        },
        {
            "id": "task847-5010927d7279489baa9e481a48b9ec6f",
            "input": "To examine the mortality risk of blood transfusions when donor information, postdonation treatment, and a wide selection of risk factors are taken into account.', 'A retrospective study was performed on 9907 patients who underwent coronary artery bypass grafting and/or aortic valve replacement. Several transfusion-related risk factors, including age of blood products, sex of donor, ABO group, Rh group, posttransfusion treatment, and sex matching, were included in the analysis. A wide selection of preoperative comorbidities were included as well. A Cox proportional hazards analysis was performed to determine significant risk factors. Patients were followed for a period of up to 12\\xa0years posttransfusion.', 'We found an excess mortality for transfusions of sex-mismatched red blood cells (RBCs) per unit transfused (hazard ratio [HR], 1.083; 95% confidence interval [CI] 1.028-1.140; P\\xa0=\\xa0.003). In addition, we found a significant risk during the first year for transfusing 1 to 2 units of non-leukocyte-depleted RBCs (HR, 1.426; 95% CI, 1.004-2.024; P\\xa0=\\xa0.047). Transfusion of 1 to 2 units of leukocyte-depleted RBCs was not associated with increased risk (HR, 0.981; 95% CI, 0.866-1.110; P\\xa0=\\xa0not significant). The age of blood products was not associated with increased mortality.",
            "output": [
                "Does transfusion of sex-mismatched and non-leukocyte-depleted red blood cells in cardiac surgery increase mortality?"
            ]
        },
        {
            "id": "task847-70e7ac4e586e458c8fa2f55b8764a6ca",
            "input": "Fructus mume (F. mume) has been used as a traditional treatment for ulcer, cough, and digestive problems for many years in Asian countries. Previous studies have demonstrated that F. mume extracts alleviate cognitive deficits in rats with chronic cerebral hypoperfusion and in mice with scopolamine treatments. The present experiment was conducted to examine the effects of F. mume on cognitive impairments in 5XFAD transgenic mice with five familial Alzheimer's disease (AD) mutations.\", 'F. mume was administered daily to 5XFAD mice at 12 weeks of age and continued for 90 days. Cognitive function was evaluated using a spatial memory version of the Morris water maze task, the object/location novelty recognition test, and contextual fear conditioning at 24 weeks of age. To elucidate the possible mechanisms underlying the memory improving effects of F. mume in 5XFAD mice, we examined alterations in hippocampal cholinergic function.', 'Vehicle-treated 5XFAD mice exhibited hippocampus-dependent memory impairments compared with non-transgenic littermates, which was reversed in F. mume-treated 5XFAD mice. In addition, reduced hippocampal choline acetyltransferase (ChAT) levels in 5XFAD mice were reversed by F. mume treatment, indicating that F. mume enhances the effects of cholinergic neuronal function.",
            "output": [
                "Do fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice?"
            ]
        },
        {
            "id": "task847-d05f7278f236432babfb57bad4013b01",
            "input": "To develop a quantitative histopathology algorithm to predict which patients with cutaneous squamous cell carcinoma (cSCC) were likely to experience recurrence or metastases.', 'This retrospective study of cSCC lesions compared patients with aggressive disease (n = 40) and those with nonaggressive disease (n = 35). Based on a previous study using nuclear karyometry, we determined that aggressive lesions had a high proportion of a specific nuclear phenotype. The proportion of those nuclei was used to derive an aggressiveness score for each lesion. The mean age of patients was similar in both groups, as were the locations of index lesions.', 'The mean aggressiveness scorefor cases with aggressive lesions was 0.60 \u00b1 0.21 and was 0.28 \u00b1 0.35 for those with nonaggressive lesions. The overall accuracy in properly characterizing lesions was 72%. The area under the receiver operating characteristic curve was 0.80 \u00b1 0.05. In general, the aggressive nuclear phenotype is represented by elevated levels of chromatin clumps and short linear segments of dark chromatin/intense pixels.",
            "output": [
                "Does high Proportion of Nuclear Phenotype identify Aggressive Cutaneous Squamous Cell Carcinoma?"
            ]
        },
        {
            "id": "task847-917035112bbc4e8cb1406340fcc79c44",
            "input": "A metaanalysis was performed to investigate the association between serum osteopontin (OPN) levels and the clinical pathological features in non-small cell lung cancer (NSCLC) patients.', 'A systematic literature search was performed to identify relevant studies published prior to September 2014 using PubMed and China National Knowledge Infrastructure databases. Data extracted from the selected studies were analyzed using statistical software.', 'Based on our stringent selection criteria only 10 studies contained a combined total of 1,135 NSCLC patients. Our metaanalysis results clearly showed a strong correlation between serum OPN levels and multiple tumor parameters, such as TNM stage, histologic grade, and lymph node metastasis in NSCLC (TNM stage: RR = 0.69, 95% CI 0.62-0.77, p < 0.001; histologic grade: RR = 1.24, 95% CI 1.04-1.48, p = 0.016; lymph node metastasis: RR = 1.69, 95% CI 1.48 - 1.93, p < 0.001).",
            "output": [
                "Do serum Osteopontin Levels Correlate with Clinical and Pathological Features in Non-Small Cell Lung Cancer?"
            ]
        },
        {
            "id": "task847-ad48a9e8d0424ed4b78aeef482dbb132",
            "input": "A major concern of using phosphodiesterase (PDE) inhibitors in heart failure is their potential to increase mortality by inducing arrhythmias. By diminishing cyclic adenosine monophosphate (cAMP) hydrolysis, they promote protein kinase A (PKA) activity under \u03b2-adrenergic receptor (\u03b2-AR) stimulation, hence enhancing Ca(2+) cycling and contraction. Yet, cAMP also activates CaMKII via PKA or the exchange protein Epac, but it remains unknown whether these pathways are involved in the pro-arrhythmic effect of PDE inhibitors.', 'Excitation-contraction coupling was investigated in isolated adult rat ventricular myocytes loaded with Fura-2 and paced at 1 Hz allowing coincident measurement of intracellular Ca(2+) and sarcomere shortening. The PDE4 inhibitor Ro 20-1724 (Ro) promoted the inotropic effects of the non-selective \u03b2-AR agonist isoprenaline (Iso) and also spontaneous diastolic Ca(2+) waves (SCWs). PDE4 inhibition potentiated RyR2 and PLB phosphorylation at specific PKA and CaMKII sites increasing sarcoplasmic reticulum (SR) Ca(2+) load and SR Ca(2+) leak measured in a 0Na(+)/0Ca(2+) solution \u00b1 tetracaine. PKA inhibition suppressed all the effects of Iso \u00b1 Ro, whereas CaMKII inhibition prevented SR Ca(2+) leak and diminished SCW incidence without affecting the inotropic effects of Ro. Inhibition of Epac2 but not Epac1 diminished the occurrence of SCWs. PDE3 inhibition with cilostamide induced an SR Ca(2+) leak, which was also blocked by CaMKII inhibition.",
            "output": [
                "Does calmodulin kinase II inhibition limit the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors?"
            ]
        },
        {
            "id": "task847-16b172c47cf1405d8c3cdfb9fcedda75",
            "input": "Low vitamin D levels have been associated with obesity and living in areas that lack sunshine, such as northern Europe. The aim of this study was to investigate the vitamin D status of a group of obese children in Sweden and to investigate the associations between vitamin D status and markers of glucose metabolism and metabolic risk markers.', 'This was a prospective cross-sectional study of 202 obese children between 4.5 and 17.9 years of age who had been referred to the National Childhood Obesity Centre at Karolinska University Hospital, Stockholm. We examined age, gender, 25-hydroxyvitamin D (25(OH)D), f-glucose, f-insulin and metabolic risk markers. Vitamin D deficiency was defined as less than 30 25(OH)D nmol/L. Children with and without a vitamin D deficiency were compared.', 'Just over a third (33.2%) of our study population had vitamin D levels <30 nmol/L 25(OH)D. A significant interaction effect was found between age and 25(OH)D. An association was also found between low 25(OH)D levels and impaired fasting glycaemia (IFG) independent of age and season.",
            "output": [
                "Is vitamin D deficiency associated with prediabetes in obese Swedish children?"
            ]
        },
        {
            "id": "task847-57d0fa2b82074d7b936370b5485fa2d9",
            "input": "The antidepressant drug fluoxetine (FLU) is considered in the group of selective serotonine re-uptake inhibitors. Its distribution in brain and binding to human brain glutathione S-transferase-\u03c0 (GST-\u03c0) have been shown. FLU can cross blood brain barrier and placenta, accumulate in fetus and may cause congenital malformations.', 'To elucidate the interaction of placental GST-\u03c0 with FLU.', 'First, concentration-dependent inhibition of human placental GST-\u03c0 was evaluated by using different FLU concentrations and then 0.3125, 0.625, 1.25, 2.5 and 5\\u2009mM FLU concentrations were chosen and tested while keeping GSH concentration constant and 1-chloro-2,4-dinitrobenzene (CDNB) concentration varied and vice versa. The data were evaluated with different kinetic models and Statistica 9.00 for Windows.', 'The Vm, at variable [CDNB] (142\\u2009\u00b1\\u200916\\u2009U/mg protein) was 3 times higher than the Vm obtained at variable [GSH] (49\\u2009\u00b1\\u20094\\u2009U/mg protein). On the other hand, the Km for CDNB was \u223c10 times higher than the Km for GSH (1.99\\u2009\u00b1\\u20090.36\\u2009mM versus 0.21\\u2009\u00b1\\u20090.06\\u2009mM). The IC50 value for FLU was 8.6\\u2009mM. Both at constant [CDNB] and variable [GSH] and at constant [GSH] and variable [CDNB] the inhibition types were competitive with the Ki values of 5.62\\u2009\u00b1\\u20094.37 and 8.09\\u2009\u00b1\\u20091.27\\u2009mM, respectively.",
            "output": [
                "Does fluoxetine-induced toxicity result in human placental glutathione S-transferase-\u03c0 ( GST-\u03c0 ) dysfunction?"
            ]
        },
        {
            "id": "task847-635f09bae0774af58137a37399fbc842",
            "input": "Glaucoma is a complex neurodegeneration and a leading cause of blindness worldwide. Current therapeutic strategies, which are all directed towards lowering the intraocular pressure (IOP), do not stop progression of the disease. We have demonstrated that recombinant adeno-associated virus (rAAV) gene delivery of a form of erythropoietin with attenuated erythropoietic activity (EpoR76E) can preserve retinal ganglion cells, their axons, and vision without decreasing IOP. The goal of this study was to determine if modulation of neuroinflammation or oxidative stress played a role in the neuroprotective activity of EPO.R76E.', 'Five-month-old DBA/2J mice were treated with either rAAV.EpoR76E or a control vector and collected at 8 months of age. Neuroprotection was assessed by quantification of axon transport and visual evoked potentials. Microglia number and morphology and cytokine and chemokine levels were quantified. Message levels of oxidative stress-related proteins were assessed.', 'Axon transport and visual evoked potentials were preserved in rAAV.EpoR76E-treated mice. The number of microglia was decreased in retinas from 8-month-old rAAV.EpoR76E-treated mice, but proliferation was unaffected. The blood-retina barrier was also unaffected by treatment. Levels of some pro-inflammatory cytokines were decreased in retinas from rAAV.EpoR76E-treated mice including IL-1, IL-12, IL-13, IL-17, CCL4, and CCL5. TNF\u03b1 messenger RNA (mRNA) was increased in retinas from 8-month-old mice compared to 3-month-old controls regardless of treatment. Expression of several antioxidant proteins was increased in retinas of rAAV.EpoR76E-treated 8-month-old mice.",
            "output": [
                "Does virus-mediated EpoR76E gene therapy preserve vision in a glaucoma model by modulating neuroinflammation and decreasing oxidative stress?"
            ]
        },
        {
            "id": "task847-858cbd563d174340a0be091513afe1b7",
            "input": "Centella asiatica (CA) leaves extract has been shown therapeutic potential. However, safety information is lacking.', 'To evaluate acute oral toxicity (AOT), sub-chronic toxicity, and mutagenic potential of standardized extract of CA (L.) Urban leaves (INDCA).', 'For the acute toxicity study, INDCA was orally administered to Sprague-Dawley rats at a dose range of 0-2000 mg/kg. For the repeated dose toxicity study, the rats of either sex were orally administered with INDCA at the doses of 250, 500, and 1000 mg/kg/day for a period of 90 days. The effects on body weight, food and water consumption, organ weight, hematology, clinical chemistry as well as histology were studied. The mutagenic potential of INDCA was tested using reverse mutation assay (Ames test).', \"Data of each parameter were analyzed by one-way ANOVA followed by Dunnett's test to compare the difference between treated groups.\", 'The administration of INDCA did not produce mortality or significant changes in the clinical signs included but not limited to changes in the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavior pattern. The appearance, progress, and disappearance of these signs were recorded. The lethal dose and no observable adverse effect level of INDCA were 2000 mg/kg and 1000 mg/kg, respectively. There were no significant differences in the organ weights, hematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. It was found to be nonmutagenic in reverse mutation assay.",
            "output": [
                "Does preclinical Safety Assessment of Standardized Extract of Centella asiatica ( L. ) Urban leave?"
            ]
        },
        {
            "id": "task847-ff65ea8e7c48454cb812a5d0192e01b1",
            "input": "The present study was designed to investigate underlying molecular mechanism for antitumorigenic potential of Terminalia chebula (TC) against chemically-induced skin tumorigenesis in Swiss albino mice. It is used as herbal medicine because it exhibits antioxidant, anti-inflammatory, and anticarcinogenic activity. However, the pr\u00e9cised underlying mechanism remains to be elucidated.', 'In light of the important role of nuclear factor-kappaB (NF-\u03baB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (i-NOS), ornithine decarboxylase (ODC), proinflammatory cytokines, oxidative stress in carcinogenesis, chemopreventive efficacy of TC against 7,12-dimethylbenz[a] anthracene (DMBA), and croton oil-induced 2-stage skin carcinogenesis was studied in terms of cytoprotective antioxidant enzymes activity, lipid peroxidation (LPO), inflammatory responses, and expression of various molecular markers in skin tissues.', 'We found that topical application of TC at dose of 30 mg/kg b. wt. mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Histological findings further supported the protective effects of TC against DMBA/croton oil-induced cutaneous damage.",
            "output": [
                "Does terminalia Chebula attenuate DMBA/Croton Oil-Induced Oxidative Stress and Inflammation in Swiss albino Mouse Skin?"
            ]
        },
        {
            "id": "task847-bb55e2ba03374a809987c11cb9b1c94a",
            "input": "Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels.', 'Participants were selected from BetaGene (n = 1,023), a study of insulin resistance and pancreatic \u03b2-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO2, O3, and PM2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NOx. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits.', 'Short-term (up to 58 days cumulative lagged averages) exposure to PM2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P \u2264 0.036). Annual average PM2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C (P \u2264 0.043). The effects of short-term PM2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes.",
            "output": [
                "Do ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans?"
            ]
        },
        {
            "id": "task847-abe5e5e1588345fda6f53f89c895b94a",
            "input": "Brain structures underlying posttraumatic stress disorder (PTSD) have been a focus of imaging studies, but associations between treatment outcome and alterations in brain structures remain largely unexamined. We longitudinally examined the relation of structural changes in the rostral anterior cingulate cortex (rACC), a previously identified key region in the PTSD fear network, to outcome of prolonged exposure (PE) treatment.', 'The sample included 78 adults (53 women): 41 patients with PTSD and 37 trauma-exposed healthy volunteers (TE-HCs). Patients underwent a 10-week course of PE treatment and completed pre- and posttreatment assessments and magnetic resonance imaging (MRI) structural scans. TE-HCs also underwent assessment and MRI at baseline and 10 weeks later. PE remitters (n\\xa0=\\xa011), nonremitters (n\\xa0=\\xa014), and TE-HCs, were compared at baseline on demographic and clinical characteristics and ACC structure. Remitters, nonremitters, and TE-HCs were compared for pre- to posttreatment clinical and structural ACC change, controlling for potential confounding variables.', 'There were no baseline differences in structure between PTSD and TE-HCs or remitters and nonremitters. Following treatment, PTSD remitters exhibited cortical thinning and volume decrease in the left rACC compared with PTSD nonremitters and TE-HCs.",
            "output": [
                "Does pTSD REMISSION AFTER PROLONGED EXPOSURE TREATMENT be ASSOCIATED WITH ANTERIOR CINGULATE CORTEX THINNING AND VOLUME REDUCTION?"
            ]
        },
        {
            "id": "task847-1fbeed3c77a9430f9e8b063b50700832",
            "input": "Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by a mutation in DMD encoding dystrophin. Oxidative stress accounts for dystrophic muscle pathologies in DMD. We examined the effects of molecular hydrogen in mdx mice, a model animal for DMD.', 'The pregnant mother started to take supersaturated hydrogen water (>5\\u2005ppm) ad libitum from E15.5 up to weaning of the offspring. The mdx mice took supersaturated hydrogen water from weaning until age 10 or 24 weeks when they were sacrificed.', 'Hydrogen water prevented abnormal body mass gain that is commonly observed in mdx mice. Hydrogen improved the spontaneous running distance that was estimated by a counter-equipped running-wheel, and extended the duration on the rota-rod. Plasma creatine kinase activities were decreased by hydrogen at ages 10 and 24 weeks. Hydrogen also decreased the number of central nuclei of muscle fibers at ages 10 and 24 weeks, and immunostaining for nitrotyrosine in gastrocnemius muscle at age 24 weeks. Additionally, hydrogen tended to increase protein expressions of antioxidant glutathione peroxidase 1, as well as anti-apoptotic Bcl-2, in skeletal muscle at age 10 weeks.",
            "output": [
                "Does molecular hydrogen alleviate motor deficits and muscle degeneration in mdx mice?"
            ]
        },
        {
            "id": "task847-ae03119bf7394273be0cf72b8de11a4a",
            "input": "Innate and adaptive immune responses change with increasing age and affect the course of diseases. Previous study investigated immunologic alteration in Western nasal polyps (NP) which is mostly eosinophilic. However, there are no reports regarding age-related immune changes of non-eosinophilic NP (NE-NP) which is a predominant subtype in Asian population.', 'A total of 153 subjects, including 20 with control, 63 with chronic rhinosinusitis (CRS) without NP (CRSsNP), and 70 with CRS with NP were enrolled. Age-related changes in computed tomography (CT), cytokines and clinical information were investigated. Tissue samples were analyzed for protein levels of IL-5, IL-17A, IL-23, interferon (IFN)-\u03b3, CCL-11, and CXCL-8, using Luminex immunoassay and for mRNA expression levels of interleukin (IL)-5, IL-17A, IL-23p19, IFN-\u03b3, CCL-11, CXCL-1, CXCL-2, CXCL-8, and CXCR2 by quantitative RT-PCR. Immunohistochemistry (IHC) was performed for the number of inflammatory cells.', 'We observed that Lund-Mackay CT scores decreased with age in NE-NP. The number of human neutrophil elastase-positive cells and myeloperoxidase gene expression decreased in older patients with NE-NP, but not in control subjects, CRSsNP, and E-NP. Neutrophil-associated cytokines including IL-17A and IL-23, were negatively correlated with age in NE-NP at the protein and mRNA levels. Additionally, the expression of CXCR2, a receptor for CXCL-1 and CXCL-2, was decreased with age in NE-NP. However, there were no age-related changes in blood neutrophil count, and neutrophil-recruiting chemokines such as CXCL-1, CXCL-2, and CXCL-8. Elderly NE-NP patients showed better endoscopic scores at 12 months after surgery compared with the non-elderly.",
            "output": [
                "Does age-Related Decline of Neutrophilic Inflammation be Associated with Better Postoperative Prognosis in Non-eosinophilic Nasal Polyps?"
            ]
        },
        {
            "id": "task847-8e1ef48591ba43e0999165c06a91b252",
            "input": "Recent studies suggest that the inconsistent outcomes of patellofemoral pain (PFP) treatment may result from the unclear understanding of changes in the structures remote from the knee joint. Due to the crucial influence of core stability on the knee function, this study aimed to evaluate the recruitment pattern of core muscles in individuals with and without PFP.', 'Sixty women aged 18 to 40years, including 30 subjects diagnosed with PFP and 30 healthy controls rose on to their toes as quickly and strongly as possible in response to a sound alarm in standing position. Electromyographic onsets of the transversus abdominis (TrA)/internal oblique (IO), erector spinae (ES), and gluteus medius (GM) muscles were expressed relative to the electromyographic onset of the prime mover (i.e. soleus). Independent t-tests were performed to compare the onsets of each muscle between the groups. The nonparametric Friedman test and the post-hoc of Wilcoxon signed-rank test were used to describe the muscle activation pattern within the groups.', 'The results revealed different recruitment patterns of the core muscles between the groups. In the healthy group the GM and TrA/IO contracted, almost simultaneously, in anticipation of the prime mover contraction (sol). However, in PFP subjects a significant delay in the contraction of TrA/IO changed the pattern of muscle activation.",
            "output": [
                "Does core muscle recruitment pattern during voluntary heel raise is different between patients with patellofemoral pain and healthy individuals?"
            ]
        },
        {
            "id": "task847-49ab9d09849d402089162d46ab2a384e",
            "input": "Childhood trauma is a risk factor for personality disorder. We have previously shown that childhood trauma is associated with increased central corticotrophin-releasing hormone concentration in adults with personality disorder. In the brain, the release of corticotrophin-releasing hormone can be stimulated by noradrenergic neuronal activity, raising the possibility that childhood trauma may affect the hypothalamic-pituitary adrenal (HPA) axis by altering brain noradrenergic function. In this study, we sought to test the hypothesis that childhood trauma is associated with blunted growth hormone response to the \u03b1-2 adrenergic autoreceptor agonist clonidine.', 'All subjects provided written informed consent. Twenty personality disordered and twenty healthy controls (without personality disorder or Axis I psychopathology) underwent challenge with clonidine, while plasma Growth Hormone (GH) concentration was monitored by intravenous catheter. On a different study session, subjects completed the Childhood Trauma Questionnaire and underwent diagnostic interviews.', 'Contrary to our a priori hypothesis, childhood trauma was associated with enhanced GH response to clonidine. This positive relationship was present in the group of 40 subjects and in the subgroup 20 personality disordered subjects, but was not detected in the healthy control subjects when analyzed separately. The presence of personality disorder was unrelated to the magnitude of GH response.",
            "output": [
                "Does gH response to intravenous clonidine challenge correlate with history of childhood trauma in personality disorder?"
            ]
        },
        {
            "id": "task847-77abbe08938948bba95cf2cb4d4be704",
            "input": "Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs.', 'First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214.', 'MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214.",
            "output": [
                "Does miR-214 attenuate Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1?"
            ]
        },
        {
            "id": "task847-2f7ec9ae89134335a698055a72e4d46b",
            "input": "Patients undergoing major vascular surgery often develop postoperative pneumonia that impacts their outcomes. Conflicting data exist concerning the potential benefit of tapered-shaped cuffs on tracheal sealing. The primary objective of this study was to assess the efficiency of a polyvinyl chloride tapered-cuff endotracheal tube at reducing the postoperative pneumonia rate after major vascular surgery. Secondary objectives were to determine its impact on microaspiration, ventilator-associated pneumonia rate, and inner cuff pressure.', 'This prospective randomized controlled study included 109 patients who were randomly assigned to receive either spherical- (standard cuff) or taper-shaped (tapered cuff) endotracheal tubes inserted after anesthesia induction and then admitted to the intensive care unit after major vascular surgery. Cuff pressure was continuously recorded over 5 h. Pepsin and \u03b1-amylase concentrations in tracheal aspirates were quantified on postoperative days 1 and 2. The primary outcome was the early postoperative pneumonia frequency.', 'Comparing the tapered-cuff with standard-cuff group, respectively, postoperative pneumonia rates were comparable (42 vs. 44%, P = 0.87) and the percentage (interquartile range) of cuff-pressure time with overinflation was significantly higher (16.1% [1.5 to 50] vs. 0.6% [0 to 8.3], P = 0.01), with a 2.5-fold higher coefficient of variation (20.2 [10.6 to 29.4] vs. 7.6 [6.2 to 10.2], P < 0.001). Although microaspiration frequencies were high, they did not differ between groups.",
            "output": [
                "Does tapered-cuff Endotracheal Tube Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery : A Randomized Controlled Trial?"
            ]
        },
        {
            "id": "task847-2dce0849b01747f088c982c05df89a6f",
            "input": "Whether the round window membrane (RWM) is permeable to iodine-based contrast agents (IBCA) is unknown; therefore, our goal was to determine if IBCAs could diffuse through the RWM using CT volume acquisition imaging.', \"Imaging of hydrops in the living human ear has attracted recent interest. Intratympanic (IT) injection has shown gadolinium's ability to diffuse through the RWM, enhancing the perilymphatic space.\", 'Four unfixed human cadaver temporal bones underwent intratympanic IBCA injection using three sequentially studied methods. The first method was direct IT injection. The second method used direct RWM visualization via tympanomeatal flap for IBCA-soaked absorbable gelatin pledget placement. In the third method, the middle ear was filled with contrast after flap elevation. Volume acquisition CT images were obtained immediately postexposure, and at 1-, 6-, and 24-hour intervals. Postprocessing was accomplished using color ramping and subtraction imaging.', 'After the third method, positive RWM and perilymphatic enhancement were observed with endolymph sparing. Gray scale and color ramp multiplanar reconstructions displayed increased signal within the cochlea compared with precontrast imaging. The cochlea was measured for attenuation differences compared with pure water, revealing a preinjection average of -1,103 HU and a postinjection average of 338 HU. Subtraction imaging shows enhancement remaining within the cochlear space, Eustachian tube, middle ear epithelial lining, and mastoid.",
            "output": [
                "Does intratympanic Iodine Contrast Injection diffuse Across the Round Window Membrane Allowing for Perilymphatic CT Volume Acquisition Imaging?"
            ]
        },
        {
            "id": "task847-3cf220446d9542909916612232298cfd",
            "input": "As a component of the outer membrane in Gram-negative bacteria, lipopolysaccharide (LPS)-induced proliferation and cell cycle progression of monocytes/macrophages. It has been suggested that the proapoptotic T-cell death-associated gene 51 (TDAG51) might be associated with cell proliferation and cell cycle progression; however, its role in the interaction between LPS and macrophages remains unclear.', 'We attempted to elucidate the role(s) of TDAG51 played in the interaction between LPS and macrophages.', 'We investigated TDAG51 expression in RAW264.7 cells stimulated with LPS and examined the effects of RNA interference-mediated TDAG51 down-regulation. We used CCK-8 assay and flow cytometry analysis to evaluate the interaction between TDAG51 and LPS-induced proliferation and cell cycle progression in RAW264.7 cells.', 'Our findings indicate that TDAG51 is up-regulated in LPS-stimulated RAW264.7 cells, the TDAG51 siRNA effectively reduced TDAG51 protein up-regulation following LPS stimulation in RAW264.7 cells, the significant changes of the proliferation and cell cycle progression of RAW264.7 cells in TDAG51 Knockdown RAW264.7 cells treated with LPS were observed.",
            "output": [
                "Is up-regulation of TDAG51 a dependent factor of LPS-induced RAW264.7 macrophages proliferation and cell cycle progression?"
            ]
        },
        {
            "id": "task847-62d6d16645ee4faeb294480aebf0f8ab",
            "input": "The molecular cross-talk between commensal bacteria and the gut play an important role in the maintenance of the intestinal homeostasis and general health. Here, we studied the impact of a major Gram-positive anaerobic bacterium of the human gut microbiota, that is, Ruminococcus gnavus on the glycosylation pattern and the production of intestinal mucus by the goblet cells.', 'Our results showed that R. gnavus E1 specifically increases the expression and the glycosylation level of the intestinal glyco-conjugates by goblet cells in the colonic mucosa of mono-associated mice with R. gnavus E1 as well as in human HT29-MTX cells. Such an effect was mediated through induction of the level of mRNA encoding for the major intestinal gel-forming mucin such as MUC2 and various glycosyltransferase enzymes.",
            "output": [
                "Does ruminococcus gnavus E1 modulate mucin expression and intestinal glycosylation?"
            ]
        },
        {
            "id": "task847-b050e55399b247b396ea1e09c93d3a8c",
            "input": "To examine the association between dysglycaemia and multiple modifiable factors measured during pregnancy.', 'The Healthy Start Study collected self-reported data on modifiable factors in early and mid-pregnancy (median 17 and 27 weeks gestation, respectively) from 832 women. Women received one point for each modifiable factor for which they had optimum scores: diet quality (Healthy Eating Index score \u226564), physical activity level (estimated energy expenditure \u2265170 metabolic equivalent task-h/week), and mental health status (Perceived Stress Scale score <6 and Edinburgh Postnatal Depression Scale score <13). Dysglycaemia during pregnancy was defined as an abnormal glucose challenge result, \u22651 abnormal results on an oral glucose tolerance test, or a clinical diagnosis of gestational diabetes. Logistic regression models estimated odds ratios for dysglycaemia as a function of each factor and the total score, adjusted for age, race/ethnicity, pre-pregnancy BMI, history of gestational diabetes, and family history of Type 2 diabetes.', 'In individual analyses, only physical activity was significantly associated with a reduced risk of dysglycaemia (adjusted odds ratio 0.67, 95% CI 0.44-1.00). We observed a significant, dose-response association between increasing numbers of optimal factors and odds of dysglycaemia (adjusted P=0.01). Compared with having no optimal modifiable factors, having all three was associated with a 73% reduced risk of dysglycaemia (adjusted odds ratio 0.27, 95% CI 0.08-0.95).",
            "output": [
                "Are diet , physical activity and mental health status associated with dysglycaemia in pregnancy : the Healthy Start Study?"
            ]
        },
        {
            "id": "task847-b290a391f4c04e01b42c29062ce3325d",
            "input": "Congenital myasthenic syndromes are rare inherited disorders characterized by fatigable weakness caused by malfunction of the neuromuscular junction. We performed whole exome sequencing to unravel the genetic aetiology in an English sib pair with clinical features suggestive of congenital myasthenia.', 'We used homozygosity mapping and whole exome sequencing to identify the candidate gene variants. Mutant protein expression and function were assessed ', 'We identified a novel homozygous missense mutation in the ",
            "output": [
                "Are mutations in the Mitochondrial Citrate Carrier SLC25A1 Associated with Impaired Neuromuscular Transmission?"
            ]
        },
        {
            "id": "task847-f3f8f695cf284b31a91cd1146f92cfb7",
            "input": "Small arteries and veins up to 7 mm can be sealed safe and divided with a bipolar sealing instrument. The results for the safe sealing of larger vessels were unsatisfactory in the past. Using an ex vivo pulmonary artery model, we aimed to investigate, if a higher compression force and duration will improve the bursting pressures in case of vessels >7 mm.', 'Heart-lung preparations (from 90 kg pigs) were removed en bloc at a slaughterhouse. The whole pulmonary artery was exposed from the pulmonary valve up to the periphery of the left lung. In the laboratory, a digital pressure sensor was implanted in the central end of the blood vessel to measure the bursting pressure (in mbar). The vessels examined were divided into three groups by diameter: 1-6 mm, 7-12 mm and >12 mm. After bipolar sealing, bursting pressures were determined by pneumatic testing. Seals were made using three equal MARSEAL instruments (Gebr\u00fcder Martin GmbH & CoKG, Tuttlingen, Germany) with a SealSafe G3 electric current and different jaw compression forces of each 35 N, 45 N, and 55 N. Bursting pressures were also measured for different compression durations (0 s, 5 s, 10 s, and 20 s) with 35 N compression. Mean bursting pressures were calculated for each group (n = 15). Groups were compared using a nonparametric test (Mann-Whitney U test). The significance level was P < 0.05.', 'Mean bursting pressures in the 1-6 mm blood vessels were 290.5 \u00b1 77.1 mbar (35 N), 323.0 \u00b1 76.0 mbar (45 N) and 301.6 \u00b1 69.9 mbar (55 N). The groups did not differ significantly. Mean bursting pressures in the 7-12 mm vessels were 108.1 \u00b1 19.1 mbar (35 N), 154.3 \u00b1 28.5 mbar (45 N), and 212.4 \u00b1 45.3 mbar (55 N). In blood vessels >12 mm in diameter, we found mean bursting pressures of 77.7 \u00b1 11.7 mbar (35 N), 117.6 \u00b1 27.1 mbar (45 N), and 166.3 \u00b1 56.6 mbar (55 N). The results for the groups with 55 N compression were significantly higher than for the other groups. A compression duration of 5 s led to significantly higher mean bursting pressures than a duration of 0 s but a duration of >5 s did not bring a further significant increase in mean bursting pressure. Histologic staining of the seal zone and microscopic examination did not reveal any differences relating to compression force.",
            "output": [
                "Does more compression improve sealing effect on larger pulmonary arteries?"
            ]
        },
        {
            "id": "task847-b1abac078151474cab83ae840e311865",
            "input": "It is not well known whether prestroke antiplatelet agents (PAs) are associated with the subtypes of ischemic stroke.', 'We screened patients in a hospital-based stroke registry. Patients who were admitted with a diagnosis of first-time ischemic stroke within 5 days of symptom onset were included. Ischemic stroke subtypes were classified in accordance with the Trial of ORG 10172 in Acute Stroke Treatment classification based on stroke mechanism: large-artery atherosclerosis (LA), cardioembolism (CE), small vessel occlusion (SVO), other determined (OC) or undetermined causes (UC). Multinomial logistic regression analyses were performed to evaluate the effect of PA on stroke subtypes before and after propensity score matching.', 'Among 3,025 patients, 748 (24.7%) were taking antiplatelet agents prior to stroke. After propensity score matching, 1,190 patients were ultimately included. The PA group was associated with strokes caused by SVO rather than LA in multinomial logistic regression of an unmatched dataset. However, multivariable analysis after propensity score matching demonstrated that PA use was associated with a higher probability of SVO and CE (OR 2.05, p < 0.001 and OR 1.62, p = 0.05, respectively) compared with LA.",
            "output": [
                "Do prestroke Antiplatelet Agents in First-Time Ischemic Stroke Are Related to Subtypes?"
            ]
        },
        {
            "id": "task847-6a12666c42b549809970d898f50f8f8b",
            "input": "The disturbance of mitochondrial functions has been considered as one of the mechanisms of pathogenesis of acute pancreatitis (AP) followed by kidney failure. This study was aimed to investigate the effects of methylene blue (MB) on pancreas and kidney mitochondrial respiratory functions during experimental acute pancreatitis in rats.', 'AP was induced by administrating sodium taurocholate into the pancreatic duct of male Wistar rats. The rats were divided into three groups: the MB group, MB (5\\u2009mg/kg) was injected intravenously 10\\u2009min prior to AP induction; the AP group, saline solution was injected intravenously 10\\u2009min prior to AP induction; and the sham operation group, isotonic sodium chlorine was used instead of sodium taurocholate. The animals were sacrificed after 24\\u2009h. The pancreas and kidney were removed for mitochondrial assay by oxygraphic and spectrophotometric methods.', 'Intravenous injection of MB did not prevent AP-induced inhibition of pancreatic mitochondrial respiration; however, MB significantly improved kidney mitochondrial respiratory functions with complex I-dependent substrates glutamate and malate. The activity of complex I of mitochondria isolated from AP-damaged kidney was increased after pretreatment with MB. However, MB did not affect AP-inhibited kidney mitochondrial respiration with succinate. MB had no protective effects on amylase activity or on urea content in serum in AP.",
            "output": [
                "Does methylene blue attenuate mitochondrial dysfunction of rat kidney during experimental acute pancreatitis?"
            ]
        },
        {
            "id": "task847-8abad97542804c92bde11e6876c165cd",
            "input": "Elevated plasma concentrations of the gut bacteria choline metabolite trimethylamine N-oxide (TMAO) are associated with atherosclerosis. However, the determinants of TMAO in humans require additional assessment.', 'We examined cardiometabolic risk factors and pathways associated with TMAO concentrations in humans.', 'A total of 283 individuals (mean \u00b1 SD age: 66.7 \u00b1 9.0 y) were included in this observational study. Plasma concentrations of trimethylamine, TMAO, choline, lipids, phospholipids, and methyl metabolites were measured.', 'Study participants were divided into 4 groups by median concentrations of TMAO and choline (4.36 and 9.7 \u03bcmol/L, respectively). Compared with the group with TMAO and choline concentrations that were less than the median (n = 82), the group with TMAO and choline concentrations that were at least the median (n = 83) was older and had lower high-density lipoprotein (HDL) cholesterol, phospholipids, and methylation potential, higher creatinine, betaine, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM), and higher percentages of men and subjects with diabetes. The difference in plasma TMAO concentrations between men and women (7.3 \u00b1 10.0 compared with 5.4 \u00b1 5.6 \u03bcmol/L, respectively) was NS after adjustment for age and creatinine (P = 0.455). The TMAO:trimethylamine ratio was higher in men (P < 0.001). Diabetes was associated with significantly higher plasma TMAO concentration (8.6 \u00b1 12.2 compared with 5.4 \u00b1 5.2 \u03bcmol/L) even after adjustments. Sex and diabetes showed an interactive effect on trimethylamine concentrations (P = 0.010) but not on TMAO concentrations (P = 0.950). Positive determinants of TMAO in a stepwise regression model that applied to the whole group were SAH, trimethylamine, choline, and female sex, whereas plasma phosphatidylcholine was a negative determinant.",
            "output": [
                "Is plasma trimethylamine N-oxide concentration associated with choline , phospholipids , and methyl metabolism?"
            ]
        },
        {
            "id": "task847-ba3a5ee8a8984c75bb4ef34eedf605d0",
            "input": "Transforming growth factor beta 1 (TGF\u03b21) is strongly induced following brain injury and polarises microglia to an anti-inflammatory phenotype. Augmentation of TGF\u03b21 responses may therefore be beneficial in preventing inflammation in neurological disorders including stroke and neurodegenerative diseases. However, several other cell types display immunogenic potential and identifying the effect of TGF\u03b21 on these cells is required to more fully understand its effects on brain inflammation. Pericytes are multifunctional cells which ensheath the brain vasculature and have garnered recent attention with respect to their immunomodulatory potential. Here, we sought to investigate the inflammatory phenotype adopted by TGF\u03b21-stimulated human brain pericytes.', 'Microarray analysis was performed to examine transcriptome-wide changes in TGF\u03b21-stimulated pericytes, and results were validated by qRT-PCR and cytometric bead arrays. Flow cytometry, immunocytochemistry and LDH/Alamar Blue\u00ae viability assays were utilised to examine phagocytic capacity of human brain pericytes, transcription factor modulation and pericyte health.', 'TGF\u03b21 treatment of primary human brain pericytes induced the expression of several inflammatory-related genes (NOX4, COX2, IL6 and MMP2) and attenuated others (IL8, CX3CL1, MCP1 and VCAM1). A synergistic induction of IL-6 was seen with IL-1\u03b2/TGF\u03b21 treatment whilst TGF\u03b21 attenuated the IL-1\u03b2-induced expression of CX3CL1, MCP-1 and sVCAM-1. TGF\u03b21 was found to signal through SMAD2/3 transcription factors but did not modify nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation. Furthermore, TGF\u03b21 attenuated the phagocytic ability of pericytes, possibly through downregulation of the scavenger receptors CD36, CD47 and CD68. Whilst TGF\u03b2 did decrease pericyte number, this was due to a reduction in proliferation, not apoptotic death or compromised cell viability.",
            "output": [
                "Does tGF-beta1 regulate human brain pericyte inflammatory processes involved in neurovasculature function?"
            ]
        },
        {
            "id": "task847-476ae6e395494abdb15e9f820d6fe790",
            "input": "The management of bloating is unclear and its relationship with patients' well-being and treatment satisfaction independent of other abdominal symptoms is uncharacterized. We evaluated the association of bloating with patient-reported outcomes.\", \"Thirty-nine centers for functional gastrointestinal disorders joined the laxative inadequate relief survey. We enrolled 2203 consecutive outpatients with functional constipation (FC) or constipation-predominant irritable bowel syndrome (IBS-C) in two cross-sectional waves. Both wave 1 and 2 included the SF-12, the patient assessment of constipation-symptoms (PAC-SYM), and the treatment satisfaction questionnaire for medication (TSQM-2). Wave 2 only included a global rating of change (GRC) scale to assess patients' assessment of efficacy concerning treatment switches occurred in the 3 months prior to the interview. Bloating in the abdomen was defined on the basis of PAC-SYM item 3.\", 'The average age was 50.1 years (SD, 16.7) and 82.1% of patients were women. The prevalence of bloating was 91.6% (n = 1970). Bloating was associated with SF-12 Physical Composite Score (p < 0.01), SF-12 Mental Composite Score (p < 0.01), GRC (p < 0.01), Satisfaction with treatment effectiveness (p < 0.01), convenience of administration (p < 0.01), and side effects (p < 0.01) after adjustment for possible confounders.",
            "output": [
                "Is bloating associated with worse quality of life , treatment satisfaction , and treatment responsiveness among patients with constipation-predominant irritable bowel syndrome and functional constipation?"
            ]
        },
        {
            "id": "task847-56c69c485ecf466e8b37a5390d22d32e",
            "input": "To determine whether previously reported racial differences in fall rates between White and Black/African American is explained by differences in health status and neighborhood characteristics.', 'Prospective cohort.', 'Community.', 'The study included 550 White and 116 Black older adults in the Greater Boston area (mean age: 78 years; 36% men) who were English-speaking, able to walk across a room, and without severe cognitive impairment.', 'Falls were prospectively reported using monthly fall calendars. The location of each fall and fall-related injuries were asked during telephone interviews. At baseline, we assessed risk factors for falls, including sociodemographic characteristics, physiologic risk factors, physical activity, and community-level characteristics.', 'Over the mean follow-up of 1,048 days, 1,539 falls occurred (incidence: 806/1,000 person-years). Whites were more likely than Blacks to experience any falls (867 versus 504 falls per 1,000 person-years; RR [95% CI]: 1.77 [1.33, 2.36]), outdoor falls (418 versus 178 falls per 1,000 person-years; 1.78 [1.08, 2.92]), indoor falls (434 versus 320 falls per 1,000 person-years; 1.44 [1.02, 2.05]), and injurious falls (367 versus 205 falls per 1,000 person-years; 1.79 [1.30, 2.46]). With exception of injurious falls, higher fall rates in Whites than Blacks were substantially attenuated with adjustment for risk factors and community-level characteristics: any fall (1.24 [0.81, 1.89]), outdoor fall (1.57 [0.86, 2.88]), indoor fall (1.08 [0.64, 1.81]), and injurious fall (1.77 [1.14, 2.74]).",
            "output": [
                "Is fall Risk Black and White?"
            ]
        },
        {
            "id": "task847-0f0efa12f68346cea87a511554249a4a",
            "input": "Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns.', 'Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis.', 'We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres.",
            "output": [
                "Does baroreflex dysfunction in sick newborns make heart rate an unreliable surrogate for blood pressure changes?"
            ]
        },
        {
            "id": "task847-f1e076ef7bfc42af9636ea978dcea4c2",
            "input": "Galectin-3 (Gal-3) is a novel biomarker reflecting inflammation status and fibrosis involving worsening of both cardiac and renal functions.', 'The aim of this study was to evaluate the relationship between Gal-3 serum levels and microalbuminuria in a group of chronic heart failure (CHF) outpatients.', 'We enrolled CHF outpatients having stable clinical conditions and receiving conventional therapy. All patients underwent clinical evaluation, routine chemistry analysis, echocardiography, and evaluation of the urinary albumin/creatinine ratio (UACR).', 'Among the patients enrolled, 61 had microalbuminuria (UACR, 30-299) and 133 normoalbuminuria (UACR, < 30). Patients with normoalbuminuria showed significantly higher levels of Gal-3 than those without (19.9 \u00b1 8.8 vs. 14.6 \u00b1 5.5 ng/mL). The stepwise regression analysis indicated that Gal-3 was the first determinant of microalbuminuria (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02 - 1.14, P = 0.012), followed by diabetes (OR 2.14; 95% CI: 1.00 - 4.57; P = 0.049) and high central venous pressure (OR 2.80; 95% CI: 1.04 - 7.58; P= 0.042).",
            "output": [
                "Do galectin-3 Serum Levels Are Independently Associated With Microalbuminuria in Chronic Heart Failure Outpatients?"
            ]
        },
        {
            "id": "task847-059760c805f84841a89bfad93241f3cf",
            "input": "Amino acid substitutions within the AdeRS two-component system are believed to result in overexpression of the AdeABC efflux pump and extensive resistance to antibiotics in clinical Acinetobacter baumannii isolates. However, the exact amino acid substitutions in AdeRS that cause overexpression of the AdeABC efflux pump remain unclear. We elucidated the role of amino acid substitutions in AdeRS by a complementation assay in an adeRS knockout strain of A. baumannii.', 'Five types of adeRS operon from tigecycline-resistant XDR A. baumannii (XDRAB) were cloned and introduced into the adeRS knockout strain to reverse its tigecycline susceptibility.', 'Through shuffling gene segments among those five adeRS operons and performing site-directed mutagenesis, we found that the specific amino acid substitution Gly186Val in AdeS is crucial for reducing tigecycline susceptibility of A. baumannii.",
            "output": [
                "Does single amino acid substitution Gly186Val in AdeS restore tigecycline susceptibility of Acinetobacter baumannii?"
            ]
        },
        {
            "id": "task847-2c228ab71dbf4dcab66df21d2c550c0b",
            "input": "Accumulation of advanced glycation end products (AGEs) contributes to the development of diabetic ulcers. Recent evidence indicates that AGEs administration enhanced autophagy in many cell types. As a positive trigger of autophagy, the effect of AGEs on autophagy in skin tissues and fibroblasts remains unknown.', 'Skin tissues were isolated from Spreqne-Dawley rats and immunohistochemical staining was performed to analyze the location of LC3 and FOXO1 in skin tissues. Then primary cultured foreskin fibroblast cells with treated with AGEs and the effect of AGEs on autophagy was investigated. Protein level expressions of LC3, Beclin-1 and FOXO1 in fibroblasts were analyzed by Western blotting. Autophagic flux is detected with autophagy inhibitor chloroquine and mRFP-GFP-LC3 tandem construct.', 'Compared with skin from normal rats, immunohistochemical staining shows a predominant LC3 localization in fibroblasts cytoplasm in diabetic rats. Elevated expression of FOXO1 also existed in diabetic rats dermis fibroblasts when compared with normal rats in immunohistochemical analysis. In human skin fibroblasts cells, AGEs administration stimulated the autophagy related LC3-II/LC3-I and Beclin-1 expressions and increased autophagy flux. In mRFP-GFP-LC3 puncta formation assays, both autolysosome and autophagosome were increased in human fibroblasts after treatment with AGEs. Fibroblasts exposed to AGEs also have increased FOXO1 expression compared with control group.",
            "output": [
                "Do aGEs trigger autophagy in diabetic skin tissues and fibroblasts?"
            ]
        },
        {
            "id": "task847-59757c85269e4f749316561a1c09f6f9",
            "input": "We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA).', 'Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care.', 'Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36).",
            "output": [
                "Does early Remission be a Realistic Target in a Majority of Patients with DMARD-naive Rheumatoid Arthritis?"
            ]
        },
        {
            "id": "task847-d924fc2b3619480bac4758df92db25c7",
            "input": "Phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) pathway activation may promote neuronal survival via neuroprotection during inflammation after cerebral ischemia. In this study, we investigated whether IV pretreatment with emulsified isoflurane (EI) could decrease ischemic brain injury related to the PI3K/Akt pathway.', 'Male Sprague-Dawley rats received different doses of IV EI (1, 2, 4, or 8 mL/kg/h) or Intralipid (8 mL/kg/h) for 30 minutes (n = 6-12 per group), followed by middle cerebral artery occlusion (MCAO) for 100 minutes to induce transient focal ischemia. The neurologic score and infarct volume were measured 48 hours after MCAO. Immunostaining, Western blot analysis, and an enzyme-linked immunosorbent assay were used to assess EI effects on the cell inflammatory response, high-mobility group box-1 release, and phosphorylated Akt (expression. LY294002, a PI3K inhibitor, was also infused into the ventricular space before EI to determine the effect of EI.', 'Four milliliters per kilogram per hour of EI reduced the infarct size (21.08 \u00b1 11.24 vs 37.09 \u00b1 10.46, P = 0.006), improved neurologic scores after MCAO (1.13 \u00b1 0.48 vs 1.95 \u00b1 0.65, P = 0.015), significantly reinforced neuronal survival (982.7 \u00b1 364.4 vs 439.8 \u00b1 278.4, P = 0.036), and inhibited CD68 macrophage/macroglial infiltration in the ischemic core (188.2 \u00b1 49.1 vs 282 \u00b1 49.4, P = 0.018) compared with the vehicle group. In the EI pretreatment group, the serum high-mobility group box-1 concentration (3.62 \u00b1 0.72 vs 5.73 \u00b1 0.65, P < 0.001) was decreased, and the cerebral phosphorylated Akt level (50.33 \u00b1 4.73 vs 37.5 \u00b1 3.11, P = 0.007) was increased at 48 hours, which was inhibited by LY294002 compared with the vehicle group (5.31 \u00b1 0.72 vs 5.73 \u00b1 0.65, P = 0.216; 43.00 \u00b1 4.84 vs 37.5 \u00b1 3.11, P = 0.091).",
            "output": [
                "Does emulsified Isoflurane protect Against Transient Focal Cerebral Ischemia Injury in Rats via the PI3K/Akt Signaling Pathway?"
            ]
        },
        {
            "id": "task847-ea7db74111c54564ac0d15c0fc0a74c9",
            "input": "D-serine, the endogenous co-agonist of N-methyl-D-aspartate receptors (NMDARs), is considered to be essential for learning and memory. The aim of the current investigation was to systematically evaluate the role of D-serine on addiction behaviors considered to be mediated by the nucleus accumbens (NAc).', 'D-Serine concentration in the NAc was measured by high-performance liquid chromatography (HPLC). Cocaine-induced behavioral sensitization and conditioned place preference (CPP) models were used to evaluate the relation between changes in serine in the nucleus accumbens and cocaine-induced behavioral effects. The expression of serine racemase (SR), D-amino acid oxidase (DAAO), the cAMP response element-binding protein (CREB) and upstream kinases, and N-methyl-D-aspartate (NMDA) receptors subunits were analyzed by western blot. Long-term depression (LTD) in the NAc was investigated by electrophysiological methods.', 'The NAc slices obtained from the behavioral sensitization rats presented significantly reduced D-serine concentrations, increased expression of DAAO, and down-regulated expression of SR in a dose-dependent manner. Furthermore, D-serine injections into the nucleus accumbens blocked the development of behavioral sensitization and caused extinction of CPP. The ERK-CREB-Fos pathway and the NMDA receptor NR2B subunits in the NAc were involved in the cocaine-induced behavioral sensitization. We also found that D-serine was essential for NMDAR-dependent LTD and D-serine-regulated LTD in a bell-shaped concentration-dependent manner. The disrupted NMDAR-dependent LTD in the NAc of cocaine-treated rats was reversed by D-serine.",
            "output": [
                "Does d-Serine in the nucleus accumbens region modulate behavioral sensitization and extinction of conditioned place preference?"
            ]
        },
        {
            "id": "task847-78e61c4fe3cf4a5180668a8ea1ab58c4",
            "input": "Basic science study using in vitro tissue testing and imaging to characterize local strains in annulus fibrosus (AF) tissue.', 'To characterize mesoscale strain inhomogeneities between lamellar and inter-/translamellar (ITL) matrix compartments during tissue shear loading.', 'The intervertebral disc is characterized by significant heterogeneities in tissue structure and plays a critical role in load distribution and force transmission in the spine. In particular, the AF possesses a lamellar architecture interdigitated by a complex network of extracellular matrix components that form a distinct ITL compartment. Currently, there is not a firm understanding of how the lamellar and ITL matrix coordinately support tissue loading.', 'AF tissue samples were prepared from frozen porcine lumbar spines and mounted onto custom fixtures of a materials testing system that incorporates optical coherence tomography (OCT) imaging to perform tissue elastography. Tissues were subjected to 20 and 40% nominal shear strain, and OCT images were captured and segmented to identify regions of interest corresponding to lamellar and ITL compartments. Images were analyzed using an optical flow algorithm to quantify local shear strains within each compartment.', 'Using histology and OCT, we first verified our ability to visualize and discriminate the ITL matrix from the lamellar matrix in porcine AF tissues. Local AF strains in the ITL compartment (22.0\\u200a\u00b1\\u200a13.8, 31.1\\u200a\u00b1\\u200a16.9 at 20% and 40% applied shear, respectively) were significantly higher than corresponding strains in the surrounding lamellar compartment (12.1\\u200a\u00b1\\u200a5.6, 15.3\\u200a\u00b1\\u200a5.2) for all tissue samples (P\\u200a<\\u200a0.05).",
            "output": [
                "Does optical Coherence Tomographic Elastography reveal Mesoscale Shear Strain Inhomogeneities in the Annulus Fibrosus?"
            ]
        },
        {
            "id": "task847-47919502bd884f14a71882d60fb95374",
            "input": "We conducted this study to analyze the values of the key cephalometric angular measurements of the mandible using 3-dimensional (3D) computed tomography scans.', 'In the 106 enrolled patients, a 3D cephalometric analysis was performed to measure the angular variables of the mandible. These values were compared between the two sides and between the two sexes.', 'The frontal measurements revealed that the mandibular body curve angle was larger on the left (Lt) side (right [Rt], 141.24\u00b17.54; Lt, 142.68\u00b16.94; P=0.002) and the gonial angle was larger on the right side (Rt, 134.37\u00b18.44; Lt, 131.54\u00b17.14; P<0.001). The sagittal measurements showed that the gonial angle was larger on the right side (Rt, 134.37\u00b18.44; Lt, 131.54\u00b17.14; P>0.05). Further, the transverse measurements revealed that the mandibular body curve angle was larger on the right side (Rt, 140.28\u00b17.05; Lt, 137.56\u00b16.23; P<0.001).",
            "output": [
                "Does cephalometric Angular Measurements of the Mandible Using Three-Dimensional Computed Tomography scan in Koreans?"
            ]
        },
        {
            "id": "task847-dfdf622f66ea4d3883cf503836ede3c9",
            "input": "The purpose of this study was to identify comprehensive hand injury patterns in different pediatric age groups and to assess their risk factors.', 'This retrospective study was conducted among patients younger than 16-year-old who presented to the emergency room of a general hospital located in Gyeonggi-do, Republic of Korea, and were treated for an injury of the finger or hand from January 2010 to December 2014. The authors analyzed the medical records of 344 patients. Age was categorized according to five groups.', 'A total of 391 injury sites of 344 patients were evaluated for this study. Overall and in each group, male patients were in the majority. With regard to dominant or non-dominant hand involvement, there were no significant differences. Door-related injuries were the most common cause in the age groups of 0 to 3, 4 to 6, and 7 to 9 years. Sport/recreational activities or physical conflict injuries were the most common cause in those aged 10 to 12 and 13 to 15. Amputation and crushing injury was the most common type in those aged 0 to 3 and 4 to 6 years. However, in those aged 10 to 12 and 13 to 15, deep laceration and closed fracture was the most common type. With increasing age, closed injuries tended to increase more sharply than open injuries, extensor tendon rupture more than flexor injuries, and the level of injury moved proximally.",
            "output": [
                "Do analysis of 344 Hand Injuries in a Pediatric Population?"
            ]
        },
        {
            "id": "task847-e2d3f5840dd64e41b65ed7bae493ba0f",
            "input": "reduced fetal movements (RFM) are experienced by 46-50% of women prior to the diagnosis of stillbirth. Empowering women with evidenced-based information regarding RFM may allow for prompt contact with a health care provider and access to appropriate management. Use of the Internet is growing in popularity as a source of pregnancy information to aid mothers\u05f3 decision-making. This study aimed to identify and examine the available online information for pregnant women regarding RFM.', 'a systematic search was performed using Google, Yahoo and Bing to identify the most popular websites giving information about RFM. The websites were assessed for readability, accountability and content using the Flesh-Kincaid ease of readability score; the Silberg criteria; and by comparison to evidence-based guidelines respectively. Chat forums were assessed using a qualitative thematic analysis.', \"70 information articles and 63 chat forums were analysed from 77 unique websites. The mean readability score was 65.7 (suitable for the average 13-15 year old) and therefore above the recommended level set for health materials; only 15 (21.4%) websites met all accountability criteria; and 43 (70%) websites contained information that was not in accordance with evidence-based recommendations. Typical questions on forums were 'Is this normal? What should I do?' and responses were 'Better safe than sorry', 'There is no harm in calling'.",
            "output": [
                "Is online information for women and their families regarding reduced fetal movements of variable quality , readability and accountability?"
            ]
        },
        {
            "id": "task847-57a5e34ba2334ca09c542fb992cf81ca",
            "input": "While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells. One concern with the use of HDAC inhibitors is that they could up-regulate human endogenous retroviruses (HERVs), as well as HIV-1, with potentially pathophysiological consequences.', 'In this study, we analysed the transcription of HERV genes in HIV-1 latency T cell (J-LAT 8.4) and monocyte (U1) models following treatment with the HDAC inhibitors, vorinostat, panobinostat and romidepsin. We examined the expression of HERV-K (HML-2) env and pol, as well as the co-opted genes HERV-W env (syncytin-1), HERV-FRD env (syncytin-2), in these cell lines. Finally, we investigated HERV expression in primary human T cells.",
            "output": [
                "Is human endogenous retrovirus ( HERV ) expression induced by treatment with the histone deacetylase ( HDAC ) inhibitors in cellular models of HIV-1 latency?"
            ]
        },
        {
            "id": "task847-0bb0136f32df4442895238922a84414b",
            "input": "To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents.', 'This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17\\xa0years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30\\xa0had hepatic steatosis \u22655% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD.', 'The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected.",
            "output": [
                "Is amino Acid Metabolism Altered in Adolescents with Nonalcoholic Fatty Liver Disease-An Untargeted , High Resolution Metabolomics Study?"
            ]
        },
        {
            "id": "task847-c6940b07d8d04a2893f19e9566b8d597",
            "input": "Polo-like kinase 1 (PLK1) controls the main cell-cycle checkpoints, suggesting utility of its inhibition for cancer treatment, including of highly proliferative pediatric cancer. This preclinical study explored the selective PLK1 inhibitor volasertib (BI 6727) alone and combined with chemotherapy in pediatric malignancies.', 'Inhibition of proliferation was explored in vitro using dimethylthiazol carboxymethoxyphenyl sulfophenyl tetrazolium (MTS) assay. Mice bearing human xenografts were treated with weekly intravenous injections of volasertib.', 'Volasertib inhibited proliferation in all 40 cell lines tested, with a mean half-maximal growth inhibitory concentration of 313 nmol/l (range: 4-5000 nmol/l). Volasertib was highly active against RMS-1 alveolar rhabdomyosarcoma xenografts, resulting in 100% tumor regression. Activity was associated with complete and prolonged G2/M arrest and subsequent apoptotic cell death. Volasertib showed synergistic activity with vincristine but antagonistic effects with etoposide.",
            "output": [
                "Does polo-like Kinase Inhibitor Volasertib exhibit Antitumor Activity and Synergy with Vincristine in Pediatric Malignancies?"
            ]
        },
        {
            "id": "task847-ecae98f436a0486eb18bd6ed5004607c",
            "input": "The combined effects of Human papillomavirus (HPV) and Herpes simplex type 1 (HSV-1) infections and their effects on cancer cell radioresistance are unexplored.', 'An HPV16-positive hypopharyngeal carcinoma cell line (UD-SCC-2) was infected with wt-HSV-1 at low multiplicity of infection (MOI) and irradiated with 2 Gy at 24 h postinfection. Viability assays and quantitative reverse-transcriptase PCR for HPV16 E6, E7, nuclear factor kappa B1, B-cell CLL/lymphoma 2 (BCL2), and caspases 3, 8 and 9 at 24, and 72 h, as well as immunocytochemistry for BCL2, caspase 3, cyclin E, mouse double minute 2 homolog (MDM2), HSV-1 and Ki-67 were performed at 144 h postirradiation.', 'At 144 h, cell viability was significantly lowered by irradiation only in uninfected cells. Infection combined with irradiation resulted in increased expression of E6, E7, BCL2 and NF-\u03baB1 at 144 h. Simultaneously, E6 and E7 were down-regulated in non-irradiated infected cells. Irradiation and infection with 0.00001 MOI separately up-regulated caspase 3 but infection with 0.0001 MOI halved its expression in irradiated cells.",
            "output": [
                "Does hSV-1 Infection modulate the Radioresponse of a HPV16-positive Head and Neck Cancer Cell Line?"
            ]
        },
        {
            "id": "task847-99d90dfd110340628edd3b538164bdbf",
            "input": "Sustained inflammation is a key feature of mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). Resident IL9-producing T cells have been found in skin infections and certain inflammatory skin diseases, but their role in MF is currently unknown.', 'We analyzed lesional skin from patients with MF for the expression of IL9 and its regulators. To determine which cells were producing IL9, high-throughput sequencing was used to identify malignant clones and Vb-specific antibodies were employed to visualize malignant cells in histologic preparations. To explore the mechanism of IL9 secretion, we knocked down STAT3/5 and IRF4 by siRNA transfection in CTCL cell lines receiving psoralen+UVA (PUVA) \u00b1 anti-IL9 antibody. To further examine the role of IL9 in tumor development, the EL-4 T-cell lymphoma model was used in C57BL/6 mice.', 'Malignant and reactive T cells produce IL9 in lesional skin. Expression of the Th9 transcription factor IRF4 in malignant cells was heterogeneous, whereas reactive T cells expressed it uniformly. PUVA or UVB phototherapy diminished the frequencies of IL9- and IL9r-positive cells, as well as STAT3/5a and IRF4 expression in lesional skin. IL9 production was regulated by STAT3/5 and silencing of STAT5 or blockade of IL9 with neutralizing antibodies potentiated cell death after PUVA treatment in vitro IL9-depleted mice exhibited a reduction of tumor growth, higher frequencies of regulatory T cells, and activated CD4 and CD8 T lymphocytes.",
            "output": [
                "Does sTAT3/5-Dependent IL9 Overexpression contribute to Neoplastic Cell Survival in Mycosis Fungoides?"
            ]
        },
        {
            "id": "task847-8788396a6aeb4c4aad9462709095bb87",
            "input": "The prevalence and clinical characteristics of familial dilated cardiomyopathy (FDCM) among patients with end stage heart failure (ESHF) has yet to be elucidated. We sought to determine the prevalence of FDCM in ESHF in the United Network for Organ Sharing (UNOS) registry and compare this with center specific data from a large tertiary teaching hospital. Patients with a banked UNOS diagnosis of dilated cardiomyopathy (DCM) whose care originated at our center then underwent detailed pedigree analysis in order to determine the true prevalence of FDCM.', 'A total of 16,091 patients with DCM from all centers were identified in the UNOS registry of whom 492 carried the diagnosis of FDCM (3.1%). Patients with the diagnosis of FDCM tended to be younger (42 versus 49 years old in idiopathic dilated cardiomyopathy (IDCM), p=0.001), were less likely to have diabetes (7.8% versus 16.5% in IDCM, p<0.0001), had slightly lower creatinine (1.2 versus 1.4 in IDCM, p=0.0001) and were more likely to have a panel reactive antibody level \u2265 20% (62.1% versus 44.7% in IDCM, p<0.0001). Consecutive living adult patients with ESHF were identified from the UNOS registry that had been treated at the Yale Center for Advanced Heart Failure (YCAHF). After excluding all diagnoses that did not include any form of non-ischemic DCM, 73 patients met the inclusion criteria. Center-specific UNOS data showed pre-pedigree analysis diagnosis of FDCM in 4.12% of patients (3 out of 73), consistent with that found in the UNOS database for all centers. However, after detailed family history and pedigree analysis, 19 (26%) of 73 patients were found to have FDCM, while the remaining 54 were found to have IDCM. Echocardiographic findings including mitral regurgitation, mitral valve annulus and left ventricular end diastolic dimension were not significantly different between groups when adjusting for multiple testing.",
            "output": [
                "Is familial dilated cardiomyopathy diagnosis commonly overlooked at the time of transplant listing?"
            ]
        },
        {
            "id": "task847-939ec8cb3e8e41fa9c98ef5d72192fc1",
            "input": "High fibroblast growth factor-23 (FGF-23) levels are associated with mortality and cardiovascular events in patients with chronic kidney disease. The aim of this cross-sectional study was to investigate the relationship between plasma FGF-23 levels and coronary artery calcification and carotid artery intima-media thickness (CA-IMT) in hemodialysis (HD) patients.', 'In this cross-sectional study, plasma intact FGF-23 levels were measured in 229 patients who underwent coronary artery calcification scores (CACs) determined by multi-slice computerized tomography and CA-IMT assessed by using high-resolution color Doppler ultrasonography.', 'Median FGF-23 was 53.5 pg/ml (IQR 30.8-249.5). Median CACs was 98 (IQR 0-531), and the frequency of patients with severe calcification (CACs > 400) was 28.8%; 27.5% of cases had no calcification. Mean CA-IMT was 0.78 \u00b1 0.20 mm, and the presence of carotid plaques was 51% with a mean length 2.1 mm. FGF-23 level was positively correlated with serum calcium (r = 0.337, p < 0.001), phosphate (r = 0.397, p < 0.001) and CACs (r = 0.218, p = 0.001). Neither CA-IMT nor the presence of carotid artery plaques correlated with FGF-23 levels. In adjusted ordinal regression analysis, FGF-23 level was an independent predictor for severe CACs together with age, gender, presence of diabetes, time on dialysis and CA-IMT (model r(2) = 0.44, p < 0.001). As a novel finding, the mean CACs was markedly higher in patients with FGF-23 level above median regardless of phosphate levels (p = 0.03).",
            "output": [
                "Are fGF-23 levels associated with vascular calcification , but not with atherosclerosis , in hemodialysis patients?"
            ]
        },
        {
            "id": "task847-a1f46bd4d74343fca4550cc77a367911",
            "input": "To evaluate the graft diameter size after one-year follow-up or more of patients Tanner II, III, and IV who were submitted to anterior cruciate ligament reconstruction.', 'Ten patients [five males (mean age: 14.4 years) and five females (mean age: 13.6 years)] with open physis and anterior cruciate ligament tear were submitted to transphyseal anterior cruciate ligament reconstruction with quadruple hamstrings graft. During the procedure, graft and tunnel size were recorded. After last clinical follow-up (range 1-11 years), an MRI study was requested and their measurements near the tibial tunnel were compared with the graft diameter measured and used during primary procedure.', 'Four patients had Tanner stage II, four patients Tanner stage III, and two Tanner IV. There were statistically significant decreases in the quadruple hamstrings graft diameter size (average of 25.3%). Mean size at time of surgery was 7.9 mm (\u00b10.87), and mean size measured at different points of follow-up evaluation was 5.9 mm (\u00b10.65).",
            "output": [
                "Does intraarticular hamstring graft diameter decrease with continuing knee growth after ACL reconstruction with open physes?"
            ]
        },
        {
            "id": "task847-41798b603b244c5ea96aac4fa0c0473c",
            "input": "We examined the association between cognitive domains and research consent capacity in PD. Our hypothesis was that research consent capacity is best predicted by executive function.', 'A cohort of 90 PD patients and 30 healthy older adults were administered the MacArthur Competence Assessment Tool for Clinical Research, Dementia Rating Scale-2, and the MoCA. Experts classified patients as either \"capable\" or \"not capable\" of providing informed consent to participate in two clinical trials.', 'MacArthur Competence Assessment Tool for Clinical Research Reasoning scores for both clinical trial types were most associated with executive functions and delayed recall. As scores on these domains improved, the odds of an expert rating of \"capable of consent\" increased.",
            "output": [
                "Does research consent capacity vary with executive function and memory in Parkinson 's disease?"
            ]
        },
        {
            "id": "task847-c76106b34b8f4a658d93c3740ca9233b",
            "input": "To characterize the functional role of SIRT6 in hepatocellular carcinoma (HCC).', 'The expression of SIRT6 in 60 paired paraffin-embedded HCC tissues and adjacent nontumoral liver tissues was examined by immunohistochemistry. The expression of SIRT6 in 101 paired frozen HCC tissues and adjacent nontumoral liver tissues was analyzed by Western blotting analysis and qPCR. The biologic consequences of overexpression and knockdown of SIRT6 in HCC cell lines were studied in vitro and in vivo', 'SIRT6 expression was frequently upregulated in clinical HCC samples, and its expression was highly associated with tumor grade (P = 0.02), tumor size (P = 0.02), vascular invasion (P = 0.004), and shorter survival (P = 0.024). Depletion of SIRT6 from multiple liver cancer cell lines inhibited their growth and induced apoptosis in vitro At the molecular level, we observed that the activation of the BCL2-associated X protein (Bax) signaling pathway, a major pathway that determines cancer cell apoptosis, is regulated by SIRT6 via its deacetylase activity. SIRT6 was recruited to the promoter of Bax, where it deacetylated histone 3 lysine 9 and suppressed its promoter activity. Binding of transcription factors (p53 and E2F-1) to Bax promoter was also generally increased in SIRT6-depleted cells. In mouse xenografts, SIRT6 suppression inhibited tumor growth and induced apoptosis. Finally, there is a negative correlation between SIRT6 and Bax mRNA expressions in human HCC samples.",
            "output": [
                "Does sIRT6 Overexpression potentiate Apoptosis Evasion in Hepatocellular Carcinoma via BCL2-Associated X Protein-Dependent Apoptotic Pathway?"
            ]
        },
        {
            "id": "task847-32f2dc86e99e471d9b69dfead685447b",
            "input": "SMAD4 loss is associated with the development of metastases and poor prognosis. We evaluated expression of SMAD4 protein and its association with tumor characteristics, including biomarkers and outcome in terms of relapse-free survival and overall survival.', 'We used 1,564 stage II/III colon cancer samples from PETACC-3 to evaluate SMAD4 expression by immunohistochemistry. SMAD4 protein expression was validated by assessing mRNA expression using available expression array data. SMAD4 expression was also studied on 34 adenomas and 10 colon cancer liver metastases with their primaries. Loss of SMAD4 immunoreactivity was defined as focal or diffuse. Cases without SMAD4 loss were subdivided into those with strong and weak expression.', 'SMAD4 protein expression was informative in 1,381/1,564 cases. SMAD4 loss was found in 293/1,381 (21%) cases. Of 1,088 cases without SMAD4 loss (79%), 530 showed weak and 558 strong expression. SMAD4 loss occurred also in adenomas, but less extensively than in carcinomas. Liver metastases followed mostly the expression pattern of the primary tumor. SMAD4 loss, including weak expression, identified patients with poor survival in stage II as well as III and in both treatment arms. SMAD4 loss was less frequent in tumors with microsatellite instability and more frequent in those with loss of heterozygosity of 18q.",
            "output": [
                "Does reduced Expression of SMAD4 be Associated with Poor Survival in Colon Cancer?"
            ]
        },
        {
            "id": "task847-803c1c86cf934cc58ad41778900af457",
            "input": "Neisseria meningitidis are common colonizers of the human nasopharynx. In some circumstances, N. meningitidis becomes an opportunistic pathogen that invades tissues and causes meningitis. While a vaccine against a number of serogroups has been in effective use for many years, a vaccine against N. meningitidis group B has not yet been universally adopted. Bacterial heat shock protein complex (HSPC) vaccines comprise bacterial HSPs, purified with their chaperoned protein cargo. HSPC vaccines use the intrinsic adjuvant activity of their HSP, thought to act via Toll-like receptors (TLR), to induce an immune response against their cargo antigens. This study evaluated HSPC vaccines from N. meningitidis and the closely related commensal N. lactamica.', 'The protein composition of N. lactamica and N. meningitidis HSPCs were similar. Using human HEK293 cells we found that both HSPCs can induce an innate immune response via activation of TLR2. However, stimulation of TLR2 or TLR4 deficient murine splenocytes revealed that HSPCs can activate an innate immune response via multiple receptors. Vaccination of wildtype mice with the Neisseria HSPC induced a strong antibody response and a Th1-restricted T helper response. However, vaccination of mice deficient in the major TLR adaptor protein, MyD88, revealed that while the Th1 response to Neisseria HSPC requires MyD88, these vaccines unexpectedly induced an antigen-specific antibody response via a MyD88-independent mechanism.",
            "output": [
                "Do heat shock protein complex vaccines induce antibodies against Neisseria meningitidis via a MyD88-independent mechanism?"
            ]
        },
        {
            "id": "task847-20a8fe3c6d214e31916088929de2dafe",
            "input": "To compare the efficacy and safety of prophylactic modalities for heterotopic ossification prevention after elbow and acetabular surgeries.', 'The retrospective chart review was conducted at the Aga Khan University Hospital and comprised record of patients who underwent open reduction and internal fixation for elbow and acetabular fractures between 2010 and 2013. Data was classified into three groups: Group A patients had received single dose of radiotherapy; Group B patients had received indomethacin, and Group C patients had not received any prophylaxis. Outcome variables included time-to-fracture healing, heterotopic ossification, non-union and wound infection.', 'Of the 104patients 70(67.3%) had elbow fractures and 34(32.7%) had acetabular fractures. Out of the 70patients with elbow fractures, 28(27%) were in Group A, 24(23%) in Group B, and 18(17%) in Group C. In Group A, 4(22%) patients had wound infection compared to 1(5.5%) patient in Group C (p=0.131). One (4%) patient in Group B and 1(5.5%) in Group C developed heterotopic ossification (p=0.486). Non-union occurred in 1(4%) patient in Group B and 1(5.5%) in Group C. Out of the 34 patients with acetabular fractures, 11(32.3%) were in Group A, 10(29.4%) in Group B, and 13(38.2%) in Group C. In Group A, 2(18.2%) patients developed wound infection. Only 1(7.6%) patient in Group C developed heterotopic ossification.",
            "output": [
                "Do prophylaxis against heterotopic ossification after elbow and acetabular fractures - Do we really need it?"
            ]
        },
        {
            "id": "task847-66a41d6a3c40487caf423f988578b77d",
            "input": "A growing body of evidence indicates a positive correlation between expression of human antimicrobial peptide leucin leucin 37 (LL-37) and progression of epithelial cancers, including prostate cancer (PCa). Although the molecular mechanisms for this correlation has not yet been elucidated, the primary function of LL-37 as a chemotactic molecule for innate immune effector cells suggests its possible association in coordinating protumorigenic mechanisms, mediated by tumor-infiltrating immune cells.', 'To investigate protumorigenic role(s) of cathelicidin-related antimicrobial peptide (CRAMP), a murine orthologue of LL-37, the present study compared tumor growth kinetics between mouse PCa cell lines with and without CRAMP expression (TRAMP-C1 and TRAMP-C1(CRAMP-sh) , respectively) in immunocompetent mice. CRAMP-mediated chemotaxis of different innate immune cell types to the tumor microenvironment (TME) was observed in vivo and confirmed by in vitro chemotaxis assay. The role of CRAMP in differentiation and polarization of immature myeloid progenitors (IMPs) to protumorigenic type 2 macrophages (M2) in TME was determined by adoptive transfer of IMPs into mice bearing CRAMP(+) and CRAMP(-) tumors. To differentiate protumorigenic events mediated by tumor-derived CRAMP from host immune cell-derived CRAMP, tumor challenge study was performed in CRAMP-deficient mice. To identify mechanisms of CRAMP function, macrophage colony stimulating factor (M-CSF) and monocyte chemoattractant protein 1 (MCP-1) gene expression was analyzed by QRT-PCR and STAT3 signaling was determined by immunoblotting.', 'Significantly delayed tumor growth was observed in wild-type (WT) mice implanted with TRAMP-C1(CRAMP-sh) cells compared to mice implanted with TRAMP-C1 cells. CRAMP(+) TME induced increased number of IMP differentiation into protumorigenic M2 macrophages compared to CRAMP(-) TME, indicating tumor-derived CRAMP facilitates differentiation and polarization of IMPs toward M2. Tumor challenge study in CRAMP deficient mice showed comparable tumor growth kinetics with WT mice, suggesting tumor-derived CRAMP plays a crucial role in PCa progression. In vitro study demonstrated that overexpressed M-CSF and MCP-1 in TRAMP-C1 cells through CRAMP-mediated autocrine signaling, involving p65, regulates IMP-to-M2 differentiation/polarization through STAT3 activation.",
            "output": [
                "Does prostate cancer-derived cathelicidin-related antimicrobial peptide facilitate macrophage differentiation and polarization of immature myeloid progenitors to protumorigenic macrophages?"
            ]
        },
        {
            "id": "task847-9c6b4b96a90d4d718f70ba1f4347c087",
            "input": "MicroRNAs play an important role in cardiac remodeling. MicroRNA 499 (miR499) is highly enriched in cardiomyocytes and targets the gene for Calcineurin A (CnA), which is associated with mitochondrial fission and apoptosis. The mechanism regulating miR499 in stretched cardiomyocytes and in volume overloaded heart is unclear. We sought to investigate the mechanism regulating miR499 and CnA in stretched cardiomyocytes and in volume overload-induced heart failure.', 'Rat cardiomyocytes grown on a flexible membrane base were stretched via vacuum to 20% of maximum elongation at 60 cycles/min. An in vivo model of volume overload with aorta-caval shunt in adult rats was used to study miR499 expression. Mechanical stretch downregulated miR499 expression, and enhanced the expression of CnA protein and mRNA after 12 hours of stretch. Expression of CnA and calcineurin activity was suppressed with miR499 overexpression; whereas, expression of dephosphorylated dynamin-related protein 1 (Drp1) was suppressed with miR499 overexpression and CnA siRNA. Adding p53 siRNA reversed the downregulation of miR499 when stretched. A gel shift assay and promoter-activity assay demonstrated that stretch increased p53 DNA binding activity but decreased miR499 promoter activity. When the miR499 promoter p53-binding site was mutated, the inhibition of miR499 promoter activity with stretch was reversed. The in vivo aorta-caval shunt also showed downregulated myocardial miR499 and overexpression of miR499 suppressed CnA and cellular apoptosis.",
            "output": [
                "Does mechanical Stretch inhibit MicroRNA499 via p53 to Regulate Calcineurin-A Expression in Rat Cardiomyocytes?"
            ]
        },
        {
            "id": "task847-f7846644fa9e4dbdbf5fc07f09f2a423",
            "input": "Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism and its polymorphisms are possibly implicated in the etiology of ischemic cerebrovascular disease (CVD). The aim of this work was to determine the association of the of D9N, N291S, and T495G polymorphisms of the LPL gene as a risk factor for the development of CVD.', 'A case-control study was conducted that included 100 patients with CVD and 120 healthy controls. All the subjects were genotyped for the D9N, N291S, and T495G polymorphisms of the LPL gene through polymerase chain reaction-restriction fragment length polymorphism, and the results were analyzed for their association with CVD.', 'The D9N genotype was not significantly correlated with CVD; the odds ratio (OR) between the control subjects and CVD patients was .29 (95% confidence interval [CI], .03-2.66; P\\u2009=\\u2009.27). The N291S polymorphism was not significantly correlated with CVD either; the OR between the control subjects and CVD patients was 1.2 (95% CI, .07-19.46; P\\u2009=\\u2009.89). And the T495G mutation was not significantly correlated with CVD; the OR between the control subjects and the CVD patients was 1.21 (95% CI, .7-2.08; P\\u2009=\\u2009.48).",
            "output": [
                "Are the D9N , N291S , and T495G Polymorphisms of the Lipoprotein Lipase Gene Associated with Cerebral Infarction?"
            ]
        },
        {
            "id": "task847-df758ab56fbe418ea1292729988fa1e9",
            "input": "MicroRNA (miR) was implicated in the tumorigenesis of many types of cancer, but no study was conducted on the exact role of miR-133 in lung cancer.', 'We have identified miR-133 as a putative regulator of FOXQ1 expression, and investigated the potential involvement of miR-133 in the migration and invasion of lung cancer cells, as well as the underlying molecular mechanism.', 'MiR-133 directly targeted and down-regulated FOXQ1 expression, which in turn reduced TGF-\u03b2 level. MiR-133 was down-regulated in lung cancer cell lines A549 and HCC827, and its re-expression significantly inhibited the migration and invasion of the lung cancer cells. Further investigation revealed that this inhibition was caused by reversing the epithelial-mesenchymal transition, evidenced by miR-133 induced elevation of epithelial marker E-cadherin, and reduction of mesenchymal marker Vimentin.",
            "output": [
                "Does expression of microRNA-133 inhibit epithelial-mesenchymal transition in lung cancer cells by directly targeting FOXQ1?"
            ]
        },
        {
            "id": "task847-f1c9b05d8fbc4b2592c9968118f0f592",
            "input": "Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sj\u00f6gren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls.\", 'Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed.', 'We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed.",
            "output": [
                "Does genome-wide DNA methylation analysis in multiple tissues in primary Sj\u00f6gren 's syndrome reveal regulatory effects at interferon-induced genes?"
            ]
        },
        {
            "id": "task847-49ccf08b711b4aaba885d4d51b031840",
            "input": "SOX2 and SOX9 are commonly overexpressed in glioblastoma, and regulate the activity of glioma stem cells (GSCs). Their specific and overlapping roles in GSCs and glioma treatment remain unclear.', 'SOX2 and SOX9 levels were examined in human biopsies. Gain and loss of function determined the impact of altering SOX2 and SOX9 on cell proliferation, senescence, stem cell activity, tumorigenesis and chemoresistance.', 'SOX2 and SOX9 expression correlates positively in glioma cells and glioblastoma biopsies. High levels of SOX2 bypass cellular senescence and promote resistance to temozolomide. Mechanistic investigations revealed that SOX2 acts upstream of SOX9. mTOR genetic and pharmacologic (rapamycin) inhibition decreased SOX2 and SOX9 expression, and reversed chemoresistance.",
            "output": [
                "Does mTOR inhibition decrease SOX2-SOX9 mediated glioma stem cell activity and temozolomide resistance?"
            ]
        },
        {
            "id": "task847-08e1fdd996e5419eabec580934854bfc",
            "input": "The aim of this study was to investigate the influence of clinicopathological and biological characteristics on prognosis, disease free survival (DFS) and overall survival (OS), of very young patients (\u226435 years of age) with breast cancer.', 'We retrospectively collected information of 150 women diagnosed with breast cancer, aged \u226435 years, who were operated and treated at two University Hospitals in Serbia between January 2009 and February 2011.', 'After a median follow up of 44 months patients \u226430 had shorter DFS and OS compared to patients aged 31-35 years (p=0.004 and p=0.037, respectively). The differences in DFS and OS were significant with decreased survival associated with higher tumor grade (p=0.005 and p=0.0001, respectively). Tumor size and number of positive nodes were predictors of outcome with decreased survival associated with higher tumor size (p=0.0019 for DFS and p<0.0001 for OS) and increasing number of nodes (p<0.0001 for both). HER 2 receptor did not seem to have a prognostic influence while patients with hormonal receptors (HRs) positive tumors had a better DFS (p=0.034) and OS (p=0.046) than those with HRs negative tumors. In univariate survival analysis, a significant difference in DFS (p=0.0003) and OS (p=0.0003) was found between patients with vs without lymphovascular invasion (LVI).",
            "output": [
                "Do young age and pathological features predict breast cancer outcome - report from a dual Institution experience in Serbia?"
            ]
        },
        {
            "id": "task847-f1a0b01692684a968250dd53b332f3a5",
            "input": "Erythropoiesis-stimulating agents (ESAs) are recommended for treating chemotherapy-induced anemia in breast cancer patients. Reduced survival rates in ESAs-treated patients have been reported, possibly due to thromboembolic complications, however the exact mechanism remains obscure. The principal activator of blood coagulation in cancer is tissue factor (TF). There are data that erythropoietin receptor (EPO-R) is expressed in tumor cells. The purpose of this study was to evaluate the expression of EPO-R and TF in loco in breast cancer.', 'The expression of EPO-R and TF was investigated in 24 invasive breast carcinoma specimens. Immunohistochemical (IHC) methodologies according to ABC technique and double-staining IHC procedure were employed utilizing antibodies against EPO-R and TF.', 'Expression of EPO-R and TF was demonstrated in the tumor cells in all breast cancer specimens. No staining for EPO-R and TF was visualized in normal breast tissue. Double staining studies revealed co-expression of both EPO-R and TF in breast cancer cells and endothelial cells.",
            "output": [
                "Are erythropoietin receptor and tissue factor coexpressed in human breast cancer cells?"
            ]
        },
        {
            "id": "task847-950df8facb704e3d8f15abc0f7431a3d",
            "input": "Prions and amyloid-\u03b2 (A\u03b2) oligomers trigger neurodegeneration by hijacking a poorly understood cellular signal mediated by the prion protein (PrP) at the plasma membrane. In early zebrafish embryos, PrP-1-dependent signals control cell-cell adhesion via a tyrosine phosphorylation-dependent mechanism.', 'Here we report that the Src family kinases (SFKs) Fyn and Yes act downstream of PrP-1 to prevent the endocytosis and degradation of E-cadherin/\u03b2-catenin adhesion complexes in vivo. Accordingly, knockdown of PrP-1 or Fyn/Yes cause similar zebrafish gastrulation phenotypes, whereas Fyn/Yes expression rescues the PrP-1 knockdown phenotype. We also show that zebrafish and mouse PrPs positively regulate the activity of Src kinases and that these have an unexpected positive effect on E-cadherin-mediated cell adhesion. Interestingly, while PrP knockdown impairs \u03b2-catenin adhesive function, PrP overexpression enhances it, thereby antagonizing its nuclear, wnt-related signaling activity and disturbing embryonic dorsoventral specification. The ability of mouse PrP to influence these events in zebrafish embryos requires its neuroprotective, polybasic N-terminus but not its neurotoxicity-associated central region. Remarkably, human A\u03b2 oligomers up-regulate the PrP-1/SFK/E-cadherin/\u03b2-catenin pathway in zebrafish embryonic cells, mimicking a PrP gain-of-function scenario.",
            "output": [
                "Is activation of zebrafish Src family kinases by the prion protein an amyloid-\u03b2-sensitive signal that prevents the endocytosis and degradation of E-cadherin/\u03b2-catenin complexes in vivo?"
            ]
        },
        {
            "id": "task847-080a8b727e9a4674a56baea1cccdb614",
            "input": "Paris polyphylla is an oriental folk medicine that has anticancer activities both in vivo and in vitro. Polyphyllin VII (PP7), a pennogenyl saponin from P. polyphylla has been found to exert strong anticancer activity. However, the underlying mechanisms are poorly understood. In the present study, the anticancer effect of polyphyllin VII against human liver cancer cells and the molecular mechanisms were investigated.', 'Cellular viability was measured by MTT assay. Apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential levels were evaluated using the InCell 2000 confocal microscope. The expression levels of apoptotic-related proteins were evaluated by Western blotting.', 'PP7 strongly inhibited the cell growth and induced apoptosis and necrosis in hepatocellular carcinoma HepG2 cells. Meanwhile, PP7 up-regulated the levels of Bax/Bcl-2, cytochrome c, the cleaved forms of caspases-3, -8, -9, and poly (ADP-ribose) polymerase in a dose- and time-dependent manner, indicating that PP7 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, PP7 provoked the production of intracellular ROS and the depolarization of mitochondrial membrane potential. Further analysis showed that PP7 significantly augmented the phosphorylation of JNK, ERK and p38, the major components of mitogen-activated protein kinase (MAPK) pathways, and the expressions of tumor suppressor proteins p53 and PTEN. In addition, PP7-induced apoptosis was remarkably attenuated by MAPK inhibitors and ROS inhibitor.",
            "output": [
                "Does polyphyllin VII induce apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways?"
            ]
        },
        {
            "id": "task847-e45ff70a50e9468c8b1bfb10f979e2bd",
            "input": "Defects in phagocytic nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) function cause chronic granulomatous disease (CGD), a primary immunodeficiency characterized by dysfunctional microbicidal activity and chronic inflammation.', 'We sought to study the effect of chronic inflammation on the hematopoietic compartment in patients and mice with X-linked chronic granulomatous disease (X-CGD).', 'We used immunostaining and functional analyses to study the hematopoietic compartment in patients with CGD.', 'An analysis of bone marrow cells from patients and mice with X-CGD revealed a dysregulated hematopoiesis characterized by increased numbers of hematopoietic progenitor cells (HPCs) at the expense of repopulating hematopoietic stem cells (HSCs). In patients with X-CGD, there was a clear reduction in the proportion of HSCs in bone marrow and peripheral blood, and they were also more rapidly exhausted after in vitro culture. In mice with X-CGD, increased cycling of HSCs, expansion of HPCs, and impaired long-term engraftment capacity were found to be associated with high concentrations of proinflammatory cytokines, including IL-1\u03b2. Treatment of wild-type mice with IL-1\u03b2 induced enhanced cell-cycle entry of HSCs, expansion of HPCs, and defects in long-term engraftment, mimicking the effects observed in mice with X-CGD. Inhibition of cytokine signaling in mice with X-CGD reduced HPC numbers but had only minor effects on the repopulating ability of HSCs.",
            "output": [
                "Does hyperinflammation in patients with chronic granulomatous disease lead to impairment of hematopoietic stem cell functions?"
            ]
        },
        {
            "id": "task847-5d4be7ebe74d4ba0980ccbcabdc2065c",
            "input": "To assess the role of the serum and glucocorticoid-regulated kinase (SGK) kinase in multiple myeloma, we ectopically expressed wild type or a phosphomimetic version of SGK into multiple myeloma cell lines. These cells were specifically resistant to the ER stress inducers tunicamycin, thapsigargin, and bortezomib. In contrast, there was no alteration of sensitivity to dexamethasone, serum starvation, or mTORC inhibitors. Mining of genomic data from a public database indicated that low baseline SGK expression in multiple myeloma patients correlated with enhanced ability to undergo a complete response to subsequent bortezomib treatment and a longer time to progression and overall survival following treatment. SGK overexpressing multiple myeloma cells were also relatively resistant to bortezomib in a murine xenograft model. Parental/control multiple myeloma cells demonstrated a rapid upregulation of SGK expression and activity (phosphorylation of NDRG-1) during exposure to bortezomib and an SGK inhibitor significantly enhanced bortezomib-induced apoptosis in cell lines and primary multiple myeloma cells. In addition, a multiple myeloma cell line selected for bortezomib resistance demonstrated enhanced SGK expression and SGK activity. Mechanistically, SGK overexpression constrained an ER stress-induced JNK proapoptotic pathway and experiments with a SEK mutant supported the notion that SGK's protection against bortezomib was mediated via its phosphorylation of SEK (MAP2K4) which abated SEK/JNK signaling. These data support a role for SGK inhibitors in the clinical setting for myeloma patients receiving treatment with ER stress inducers like bortezomib.",
            "output": [
                "Does sGK Kinase Activity in Multiple Myeloma Cells protect against ER Stress Apoptosis via a SEK-Dependent Mechanism?"
            ]
        },
        {
            "id": "task847-84398c18ef4e46d9a9b7e7a26d40d518",
            "input": "We used optical coherence tomography (OCT) and intravascular ultrasound (IVUS) to assess the struts of implanted stents in patients with acute coronary syndrome (ACS).', 'A totle of 10,756 stent struts were analyzed with OCT in 42 patients of ACS. Of them, both of IVUS and OCT imaging were performed in 33 patients. Appearance of stent struts was classified as well apposed, buried, malapposed, and nondetectable, and the number of stent struts were counted by OCT and IVUS was compared.', 'Most of stent struts were well apposed (78.1%, 8,407/10,756). However, malapposed struts were 5.6% (607/10,756), and 14.1% (1,514/10,756) of stent struts were buried by thrombus. The nondetectable struts were 2.11% (228/10,756) in ACS. 94.7% (216/228) of nondetectable stent struts were associated with red thrombus, and plaque prolapse was in 5.3% (12/228). The number of stent struts counted by OCT were larger than that of IVUS. The mean number of stent struts at the proximal and distal stent edges were 24\\u2009\u00b1\\u20096.57 in OCT, the stent struts IVUS counted were 20\\u2009\u00b1\\u20094.18 (P\\u2009<\\u20090.0001). Although the frequency of malapposed struts were similar 4.6% (376/8,248) in OCT versus 4.8% (369/7,674) in IVUS (P\\u2009=\\u20090.788). Stent struts were often buried by thrombus in ACS 15.2% (1,252/8,248) in OCT versus 9.7% (747/7,674) in IVUS; P\\u2009=\\u20090.006. The nondetectable struts were fewer in IVUS than OCT 0.2% (16/7,674) in IVUS versus 2.2% (187/8,248) in OCT; P\\u2009<\\u20090.0001.",
            "output": [
                "Does a Comparison of Intravascular Imaging Modalities for Detection of Stent strut in Acute Coronary Syndrome?"
            ]
        },
        {
            "id": "task847-251047daf0c94328a9e56534abbdb1cd",
            "input": "Despite advances in the diagnosis and management of idiopathic noncirrhotic portal hypertension, its pathogenesis remains elusive. Insight may be gained from study of early-onset familial idiopathic noncirrhotic portal hypertension, in which Mendelian mutations may account for disease. We performed exome sequencing of eight subjects from six kindreds with onset of portal hypertension of indeterminate etiology during infancy or childhood. Three subjects from two consanguineous families shared the identical rare homozygous p.N46S mutation in DGUOK, a deoxyguanosine kinase required for mitochondrial DNA replication; haplotype sharing demonstrated that the mutation in the two families was inherited from a remote common ancestor. All three affected subjects had stable portal hypertension with noncirrhotic liver disease for 6-16 years of follow-up. This mutation impairs adenosine triphosphate binding and reduces catalytic activity. Loss-of-function mutations in DGUOK have previously been implicated in cirrhosis and liver failure but not in isolated portal hypertension. Interestingly, treatment of patients with human immunodeficiency viral infection with the nucleoside analogue didanosine is known to cause portal hypertension in a subset of patients and lowers deoxyguanosine kinase levels in vitro; the current findings implicate these effects on deoxyguanosine kinase in the causal mechanism.",
            "output": [
                "Does recurrent recessive mutation in deoxyguanosine kinase cause idiopathic noncirrhotic portal hypertension?"
            ]
        },
        {
            "id": "task847-5ea1eb95760545e994c3869193901960",
            "input": "To investigate the role of zinc-alpha-2-glycoprotein (ZAG) in the early stage of diabetic nephropathy, in patients with type 2 diabetes mellitus (T2DM).', 'This cross-sectional observational study recruited patients with longstanding T2DM and healthy control subjects. Patients with T2DM were further stratified based on their urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Serum and urine concentrations of ZAG were determined using an enzyme-linked immunosorbent assay.', 'Eighty patients with T2DM and 20 healthy control subjects were enrolled in the study. Mean\\u2009\u00b1\\u2009SD concentrations of ZAG in serum and urine were both significantly higher in patients with T2DM (serum: 38.29\\u2009\u00b1\\u200922.72\\u2009mg/l; urine: 53.64\\u2009\u00b1\\u200929.48\\u2009mg/g) compared with concentrations in healthy control subjects (serum: 21.61\\u2009\u00b1\\u20098.83\\u2009mg/l; urine: 28.17\\u2009\u00b1\\u200910.64\\u2009mg/g). Serum ZAG concentration was positively correlated with serum creatinine and eGFR. Urine ZAG concentration was positively correlated with UACR. Urine concentration of ZAG in the higher eGFR group was higher than that in the normal eGFR group (41.26\\u2009\u00b1\\u200913.67 versus 32.05\\u2009\u00b1\\u20098.55\\u2009mg/g, respectively).",
            "output": [
                "Does adipokine zinc-alpha-2-glycoprotein as a novel urinary biomarker present earlier than microalbuminuria in diabetic nephropathy?"
            ]
        },
        {
            "id": "task847-c8c2074efdf64a8785fb9a51c0dc2f66",
            "input": "To examine the association between injection cocaine use, hepatitis C virus (HCV) infection, and chronic renal impairment (CRI).', 'Prospective observational cohort study of HIV-HCV coinfected patients.', 'Data from 1129 participants in the Canadian Co-Infection Cohort with baseline and follow-up serum creatinine measurements between 2003 and 2014 were analyzed. Prevalent and incident cohorts were created to examine the association between self-reported past, current, and cumulative cocaine use and chronic HCV with CRI. CRI was defined as an estimated glomerular filtration rate below 70\\u200aml/min per 1.73\\u200am. Multivariate logistic regression was used to calculate odds ratios, and discrete-time proportional-hazards models were used to calculate hazard ratios for cocaine use, in the two respective cohorts, adjusted for HCV RNA and important demographic, HIV disease stage, and comorbidity confounders.', 'Eighty-seven participants (8%) had prevalent CRI. Past injection cocaine use was associated with a two-fold greater risk of prevalent CRI [odds ratio 2.03, 95% confidence interval (CI) 0.96, 4.32]. During follow-up, 126 of 1061 participants (12%) developed incident CRI (31 per 1000 person-years). Compared to nonusers, heavy (\u2265 3\\u200adays/week) and frequent injection cocaine users (\u226575% of follow-up time) experienced more rapid progression to CRI (hazard ratio 2.65, 95% CI 1.35, 5.21; and hazard ratio 1.82, 95% CI 1.07, 3.07, respectively). There was no association between chronic HCV and CRI in either cohort.",
            "output": [
                "Does frequent injection cocaine use increase the risk of renal impairment among hepatitis C and HIV coinfected patients?"
            ]
        },
        {
            "id": "task847-8975d22c05d34f98a81d4e1bea030a7b",
            "input": "The use of sedation allows medical procedures to be performed outside the operating room while ensuring patient comfort and a controlled environment to increase the yield of the procedure. There is concern about a higher risk of adverse events with use of sedation in patients with obstructive sleep apnea.', 'We aimed to determine if the presence of obstructive sleep apnea increased the risk of hospitalization and/or health care use after patients received moderate conscious sedation for an elective, ambulatory colonoscopy.', 'We conducted a retrospective case-control database and chart review study. We compared hospital admissions, intensive care unit (ICU) admissions, and emergency room visits at 24 hours, 7 days, and 30 days in patients with obstructive sleep apnea (n\\u2009=\\u20093,860) and without obstructive sleep apnea (n\\u2009=\\u20092,374) who had undergone an elective, ambulatory colonoscopy with sedation.', 'We found no significant differences in hospital admissions, ICU admissions, or emergency room visits between the two groups at any time point within the 30 days following the procedures. In a sensitivity analysis in which we compared 827 individuals with polysomnographically confirmed sleep apnea with control subjects, there was still no difference in hospital admissions, ICU admissions, or emergency room visits in the 30 days after receiving sedation for the procedure. Outcomes were not different in individuals with various severities of obstructive sleep apnea.",
            "output": [
                "Is obstructive Sleep Apnea Associated with Higher Health Care Use after Colonoscopy under Conscious Sedation?"
            ]
        },
        {
            "id": "task847-258448e335794daea15ed095a9f13ae1",
            "input": "Oxidative stress may be involved in occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD). 8-iso-Prostaglandin F2\u03b1 (8-iso-PGF2\u03b1), an isoprostane derived from arachidonic acid via lipid peroxidation, is considered a gold standard for measuring oxidative stress. The present study aimed to investigate the ability of postoperative plasma 8-iso-PGF2\u03b1 levels to predict POD and POCD in elderly patients undergoing hip fracture surgery.', 'Postoperative plasma 8-iso-PGF2\u03b1 levels of 182 patients were measured by an enzyme-linked immunosorbent assay. We assessed the relationships between plasma 8-iso-PGF2\u03b1 levels and the risk of POD and POCD using a multivariate analysis.', 'Plasma 8-iso-PGF2\u03b1 levels and age were identified as the independent predictors for POD and POCD. Based on areas under receiver operating characteristic curve, the predictive values of 8-iso-PGF2\u03b1 were obviously higher than those of age for POD and POCD. In a combined logistic-regression model, 8-iso-PGF2\u03b1 significantly enhanced the areas under curve of age for prediction of POD and POCD.",
            "output": [
                "Are postoperative plasma 8-iso-prostaglandin F2\u03b1 levels associated with delirium and cognitive dysfunction in elderly patients after hip fracture surgery?"
            ]
        },
        {
            "id": "task847-c604fb02bec84d2c8f42d69761768a75",
            "input": "Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII) is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD) patients.', 'One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance.', 'The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin) (the natural logarithm of irisin) were UII lean body mass and patients with protein energy wasting.",
            "output": [
                "Is irisin Associated with Urotensin II and Protein Energy Wasting in Hemodialysis Patients?"
            ]
        },
        {
            "id": "task847-4b492d695c8147238ee5f60dfe5c3922",
            "input": "Observational studies suggest that an association between vegetable consumption and coronary heart disease (CHD). However, the results are inconsistent. This study aimed to investigate the daily intake of vegetables on a national level and its effect on the risk of CHD risk, as determined by the Framingham Risk Score (FRS).', 'This study was conducted a cross-sectional design of 2,510 male adults 40-64y of age who participated in the 2007-2009 Korean National Health and Nutrition Examination Survey. Daily intake of vegetable was assessed by 24-h recall, and the consumption frequency of vegetables was determined using a food frequency questionnaire. The odd ratio of CHD risk according to daily intake and frequency of vegetables was analyzed.', 'Total vegetable intake was inversely and significantly associated with the risk of CHD (Model 1: 4th vs. 1st quartile, OR = 0.74, 95% CI = 0.58-0.96, P for trend = 0.0015), and the significant relationship with CHD risk remained even after adjusting for potential confounders (Model 3: 4th vs. 1st quartile, adjusted OR [aOR] = 0.69, 95% CI = 0.49-0.95, P for trend = 0.0492). Subjects in the higher quartiles of non-salted vegetable intake had 31% lower odds of the risk of CHD compared to those in the lowest quartile after adjusting for various potential confounders in model 3 (aOR = 0.69; 95% CI = 0.49-0.97, P for trend = 0.0478). No significant associations between the frequency of vegetable intake (total, green, white and red vegetable) and the risk of CHD were found.",
            "output": [
                "Is vegetable intake associated with lower Frammingham risk scores in Korean men : Korea National Health and Nutrition Survey 2007-2009?"
            ]
        },
        {
            "id": "task847-333a8677875f483cb4676bc53a1b23d8",
            "input": "Classical strains of Salmonella enterica serovar Typhimurium (Typhimurium) predominantly cause a self-limiting diarrheal illness in humans and a systemic disease in mice. In this study, we report the characterization of a strain isolated from a blood-culture taken from a 15-year old woman suffering from invasive severe salmonellosis, refractory to conventional therapy with extended-spectrum cephalosporin (ESC).', 'The strain, named 33676, was characterized as multidrug-resistant Salmonella serogroup A by biochemical, antimicrobial and serological tests. Multilocus sequence typing (MLST) and XbaI macrorestrictions (PFGE) showed that strain 33676 belonged to the Typhimurium ST213 genotype, previously described for other Mexican Typhimurium strains. PCR analyses revealed the presence of IncA/C, IncFIIA and ColE1-like plasmids and the absence of the Salmonella virulence plasmid (pSTV). Conjugation assays showed that the ESC-resistance gene bla CMY-2 was carried on the conjugative IncF plasmid, instead of the IncA/C plasmid, as found in previously studied ST213 strains. Although the IncA/C plasmid conferred most of the observed antimicrobial resistances it was not self-conjugative; it was rather able to conjugate by co-integrating with the IncF plasmid. Strain 33676 was fully attenuated for virulence in BALB/c mice infections. Both type-three secretion system (T3SS), encoded in Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2), were functional in the 33676 strain and, interestingly, this strain produced the H2 FljB flagellin instead of the H1 FliC flagellin commonly expressed by S. enterica strains.",
            "output": [
                "Is a multi-drug resistant Salmonella Typhimurium ST213 human-invasive strain ( 33676 ) containing the bla CMY-2 gene on an IncF plasmid attenuated for virulence in BALB/c mice?"
            ]
        },
        {
            "id": "task847-08a92250d9f6436aaf76b71c97150f81",
            "input": "For digestive tract cancers, the bilirubin threshold for administration of systemic chemotherapy can be 5 or 2 mg/dL (85.5 or 34.2 \u03bcmol/L) depending upon the regimen. We examined the ability of percutaneous biliary drainage (PBD) in patients with malignant biliary obstruction to achieve these clinically relevant endpoints.', '106 consecutive patients with malignant biliary obstruction and a baseline serum bilirubin >2 mg/dL underwent PBD. Time to achieve a bilirubin of 5 mg/dL (85.5 \u03bcmol/L), 2 mg/dL (34.2 \u03bcmol/L), and survival was estimated by Kaplan-Meier analysis. Potential technical and clinical prognostic factors were subjected to univariate and multivariate analysis. Categorical variables were analyzed by the log rank test. Hazard ratios were calculated for continuous variables.', 'Median survival was 100 days (range 1-3771 days). Among 88 patients with a pre-drainage bilirubin >5 mg/dL, 62% achieved a serum bilirubin \u22645 mg/dL within 30 days and 84% within 60 days, median 21 days. Among 106 patients with a pre-drainage bilirubin >2 mg/dL, 37% achieved a serum bilirubin \u22642 mg/dL by 30 days and 70% within 60 days, median 43 days. None of the technical or clinical factors evaluated, including pre-drainage bilirubin, were significant predictors of time to achieve a bilirubin \u22642 mg/dL (p = 0.51). Size and type of biliary device were the only technical variables found to affect time to bilirubin of 5 mg/dL (p = 0.016).",
            "output": [
                "Does percutaneous biliary drainage effectively lower serum bilirubin to permit chemotherapy treatment?"
            ]
        },
        {
            "id": "task847-b1dd7ea3d3e34ca28b50c04d7ab9ec0d",
            "input": "Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF), which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function.', 'To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function.', 'Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1) were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model.', 'Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes.",
            "output": [
                "Does sequestration of Vascular Endothelial Growth Factor ( VEGF ) induce Late Restrictive Lung Disease?"
            ]
        },
        {
            "id": "task847-1260718354fa446fbb9c670d126ab9a5",
            "input": "To assess the impact of an audiovisual (AV) biofeedback on intra- and interfraction tumor motion for lung cancer patients.', 'Lung tumor motion was investigated in 9 lung cancer patients who underwent a breathing training session with AV biofeedback before 2 3T magnetic resonance imaging (MRI) sessions. The breathing training session was performed to allow patients to become familiar with AV biofeedback, which uses a guiding wave customized for each patient according to a reference breathing pattern. In the first MRI session (pretreatment), 2-dimensional cine-MR images with (1) free breathing (FB) and (2) AV biofeedback were obtained, and the second MRI session was repeated within 3-6 weeks (mid-treatment). Lung tumors were directly measured from cine-MR images using an auto-segmentation technique; the centroid and outlier motions of the lung tumors were measured from the segmented tumors. Free breathing and AV biofeedback were compared using several metrics: intra- and interfraction tumor motion consistency in displacement and period, and the outlier motion ratio.', 'Compared with FB, AV biofeedback improved intrafraction tumor motion consistency by 34% in displacement (P=.019) and by 73% in period (P<.001). Compared with FB, AV biofeedback improved interfraction tumor motion consistency by 42% in displacement (P<.046) and by 74% in period (P=.005). Compared with FB, AV biofeedback reduced the outlier motion ratio by 21% (P<.001).",
            "output": [
                "Does audiovisual Biofeedback improve Cine-Magnetic Resonance Imaging Measured Lung Tumor Motion Consistency?"
            ]
        },
        {
            "id": "task847-370da18919b3433bab231e1f5a3b7f03",
            "input": "The Tonnis radiographic classification of developmental dysplasia of the hip (DDH) has been used as a prognostic indicator for patients with walking-age DDH. The International Hip Dysplasia Institute (IHDI) classification, a new radiographic classification system, has been proposed to be more reliable by its creators. We sought to validate its reliability using independent observers, to compare it to the Tonnis method, and to assess its prognostic significance in a large cohort of patients.', 'A consecutive series of walking-age DDH patients were examined radiographically and classified by the Tonnis and IHDI schemes by 3 independent observers. Interobserver agreement was determined using the Kappa method. Clinical data were collected on patients with regard to success of closed reduction, need for later pelvic osteotomy, and presence of subsequent radiographic avascular necrosis (AVN). The prognostic value of the Tonnis and IHDI classifications to predict these clinical outcomes was determined.', 'A total of 287 hips were available for analysis of the classification schemes. In total, 235 hips underwent attempted closed reduction and were eligible for analysis of successful closed reduction, and 131 hips had >4-year follow-up and were utilized for analysis of late pelvic osteotomy and AVN. Both classifications showed excellent interobserver reliability and in general, there was nonstatistically significant better reliability for the IHDI versus the Tonnis classification. In multivariate analysis, both IHDI and Tonnis classifications were found to be predictive of successful closed reduction and need for late pelvic osteotomy. Both methods showed trends toward being predictive of AVN rate, without statistical significance.",
            "output": [
                "Is a New Radiographic Classification System for Developmental Hip Dysplasia Reliable and Predictive of Successful Closed Reduction and Late Pelvic Osteotomy?"
            ]
        },
        {
            "id": "task847-7c7738dec6554134956a36bd269167e6",
            "input": "Alcoholic liver disease (ALD) ranges from fatty liver to inflammation and cirrhosis. miRNA-155 is an important regulator of inflammation. In this study, we describe the in vivo role of miR-155 in ALD.', 'Wild-type (WT) (C57/BL6J) or miR-155 knockout (KO) and TLR4 KO mice received Lieber DeCarli diet for 5weeks. Some mice received corn oil or CCl4 for 2 or 9weeks.', 'We found that miR-155 KO mice are protected from alcohol-induced steatosis and inflammation. The reduction in alcohol-induced fat accumulation in miR-155 KO mice was associated with increased peroxisome proliferator-activated receptor response element (PPRE) and peroxisome proliferator-activated receptors (PPAR)\u03b1 (miR-155 target) binding and decreased MCP1 production. Treatment with a miR-155 inhibitor increased PPAR\u03b3 expression in na\u00efve and alcohol treated RAW macrophages. Alcohol increased lipid metabolism gene expression (FABP4, LXR\u03b1, ACC1 and LDLR) in WT mice and this was prevented in KO mice. Alcohol diet caused an increase in the number of CD163(+) CD206(+) infiltrating macrophages and neutrophils in WT mice, which was prevented in miR-155 KO mice. Kupffer cells isolated from miR-155 KO mice exhibited predominance of M2 phenotype when exposed to M1 polarized signals and this was due to increased C/EBP\u03b2. Pro-fibrotic genes were attenuated in miR-155 KO mice after alcohol diet or CCl4 treatment. Compared to WT mice, attenuation in CCl4 induced hydroxyproline and \u03b1-SMA was observed in KO mice. Finally, we show TLR4 signaling regulates miR-155 as TLR4 KO mice showed no induction of miR-155 after alcohol diet.",
            "output": [
                "Do the pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis?"
            ]
        },
        {
            "id": "task847-357e386e1a374d43b5fd21db0454e1a2",
            "input": "Hepatitis B virus (HBV) integration is common in HBV-associated hepatocellular carcinoma (HCC) and may play an important pathogenic role through the production of chimeric HBV-human transcripts. We aimed to screen the transcriptome for HBV integrations in HCCs.', 'Transcriptome sequencing was performed on paired HBV-associated HCCs and corresponding non-tumorous liver tissues to identify viral-human chimeric sites. Validation was further performed in an expanded cohort of human HCCs.', 'Here we report the discovery of a novel pre-mRNA splicing mechanism in generating HBV-human chimeric protein. This mechanism was exemplified by the formation of a recurrent HBV-cyclin A2 (CCNA2) chimeric transcript (A2S), as detected in 12.5% (6 of 48) of HCC patients, but in none of the 22 non-HCC HBV-associated cirrhotic liver samples examined. Upon the integration of HBV into the intron of the CCNA2 gene, the mammalian splicing machinery utilized the foreign splice sites at 282nt. and 458nt. of the HBV genome to generate a pseudo-exon, forming an in-frame chimeric fusion with CCNA2. The A2S chimeric protein gained a non-degradable property and promoted cell cycle progression, demonstrating its potential oncogenic functions.",
            "output": [
                "Does novel pre-mRNA splicing of intronically integrated HBV generate oncogenic chimera in hepatocellular carcinoma?"
            ]
        },
        {
            "id": "task847-1aed43f73cb642b78a22ef7617dc4a42",
            "input": "Despite accumulating evidence about the negative health effects of exposure to electromagnetic fields emitted by mobile phones, no information is available on the potential impact of radiofrequency (RF) waves on polymorphonuclear leukocytes biology.', 'Two sequential whole blood tubes were collected from 16 ostensibly healthy volunteers. After placing the former tube of each subject in a plastic rack, 1 cm from a commercial smartphone (carrier frequency, 900 MHz), a call was placed on the smartphone and a communication lasting 30 min was manually activated. The latter blood tube of each volunteer was placed in another plastic rack, for an identical period of time, avoiding close contact with sources of RF waves. A complete blood count was then assessed in all whole blood samples, using Advia 2120.', 'The 30-min exposure of blood to RF waves did not induce significant variations of total and differential leukocyte counts. A significant decrease was however observed for many neutrophils parameters, with median percentage variation of -3.9% for the lobularity index (LI), -29.8% for the myeloperoxidase index (MPXI), -0.6% for the neutrophil cluster mean x (NEUTx) and -0.7% for the neutrophil cluster mean y (NEUTy), respectively. The percentage of blood samples with reduced values after exposure to RF waves was 81% for LI, 88% for NEUTx and 100% for both MPXI and NEUTy.",
            "output": [
                "Does thirty-minutes ' exposure to smartphone call trigger neutrophil activation in vitro?"
            ]
        },
        {
            "id": "task847-5577fb4d3c054950977b71376bc3da6a",
            "input": "Coronary artery calcium (CAC) is a powerful CAD risk marker when assessed by dedicated calcium scoring CT scan. We assessed diagnostic implications of CAC visible on attenuation correction CT scans (CTAC) from SPECT/CT myocardial perfusion imaging (MPI).', 'Visual presence or absence of CAC was assessed on CTAC in 1047 consecutive patients undergoing SPECT/CT MPI. Accuracy of MPI was assessed in patients undergoing invasive coronary angiography (ICA) within 1\\xa0year (n\\xa0=\\xa0109). Outcomes were identified by retrospective chart review.', 'Prevalence of true positive SPECT/CT MPI studies was greater among patients with CAC on CTAC (70% vs 16%; p\\xa0<\\xa0.001); prevalence of false positive studies was greater among those without (68% vs 15%; p\\xa0<\\xa0.001). PPV of MPI was 0.82 in patients with CAC, but only 0.19 in those without. Within median follow-up of 27.7\\xa0months, patients with CAC had higher all-cause mortality (6% vs 0.4%; p\\xa0<\\xa0.001), more late revascularizations (8% vs 0.4%; p\\xa0<\\xa0.001), and more MI (5% vs 0.2%; p\\xa0<\\xa0.001). Hazard ratio for all-cause mortality, MI, or late revascularization was 22.7 (p\\xa0<\\xa0.001) for patients with CAC vs those without.",
            "output": [
                "Does visual identification of coronary calcifications on attenuation correction CT improve diagnostic accuracy of SPECT/CT myocardial perfusion imaging?"
            ]
        },
        {
            "id": "task847-7aad5997cd2a4a6d88808b4310a60db9",
            "input": "To study the relationship between the neoplastic cells of in situ lobular neoplasia (ILN) and ductal carcinoma in situ (DCIS) and the surrounding CD10-positive myoepithelial cells.', 'Twenty consecutive cases of ILN and 51 of DCIS were stained for CD10 using the immunoperoxidase technique. The presence of CD10-positive cells was assessed semiquantitatively on a scale of 0-3 where 0 indicates their absence and 3 indicates the presence of multiple layers, which can be focal.', 'Ninety per cent of ILN cases scored 3, compared with none of DCIS (p=0.0001). There was a significant relationship between DCIS grade and CD10 score, with the mean scores being 1.43, 0.82 and 0.5 for low, intermediate and high grade, respectively. CD10-positive cells were always present around low-grade DCIS, but absent in 27% of high-grade cases. CD10-positive cells were more frequent in ER-positive than in ER-negative DCIS, and in HER2-negative than in HER2-positive cases, but the difference was not statistically significant.",
            "output": [
                "Are cD10-positive myoepithelial cells usually prominent around in situ lobular neoplasia of the breast and much less prominent or absent in DCIS?"
            ]
        },
        {
            "id": "task847-752c94ee38c84324bc4140dce0797443",
            "input": "The initial steps in the cascade leading to cell death are still unknown because of the limitations of the existing methodology, strategy, and modalities used.', 'Imaging mass spectrometry (IMS) was used to measure dynamic molecular changes of phosphatidylcholine (PC) species in the rat hippocampus after transient global ischemia (TGI) for 6min. Fresh frozen sections were obtained after euthanizing the rats on Days 1, 2, 4, 7, 10, 14, and 21. Histopathology and IMS of adjacent sections compared morphological and molecular changes, respectively.', 'Histopathological changes were absent immediately after TGI (at Day 1, superacute phase). At Days 2-21 after TGI (from subacute to chronic phases), histopathology revealed neuronal death associated with gliosis, inflammation, and accumulation of activated microglia in CA1. IMS detected significant molecular changes after TGI in the same CA1 domain: increase of PC (diacyl-16:0/22:6) in the superacute phase and increase of PC (diacyl-16:0/18:1) in the subacute to chronic phases.",
            "output": [
                "Does imaging mass spectrometry detect dynamic changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia?"
            ]
        },
        {
            "id": "task847-0888bc606d0d427db2bfebe949f9ac78",
            "input": "Circular RNAs are a subclass of non-coding RNAs detected within mammalian cells. This study was designed to test the roles of a circular RNA circ-Foxo3 in senescence using in vitro and in vivo approaches.', 'Using the approaches of molecular and cellular biology, we show that a circular RNA generated from a member of the forkhead family of transcription factors, Foxo3, namely circ-Foxo3, was highly expressed in heart samples of aged patients and mice, which was correlated with markers of cellular senescence. Doxorubicin-induced cardiomyopathy was aggravated by ectopic expression of circ-Foxo3 but was relieved by silencing endogenous circ-Foxo3. We also found that silencing circ-Foxo3 inhibited senescence of mouse embryonic fibroblasts and that ectopic expression of circ-Foxo3 induced senescence. We found that circ-Foxo3 was mainly distributed in the cytoplasm, where it interacted with the anti-senescent protein ID-1 and the transcription factor E2F1, as well as the anti-stress proteins FAK and HIF1\u03b1.",
            "output": [
                "Does foxo3 circular RNA promote cardiac senescence by modulating multiple factors associated with stress and senescence responses?"
            ]
        },
        {
            "id": "task847-22edd2258aa94916bcee471d69410ecc",
            "input": "Allergic rhinitis (AR) is a complex chronic inflammatory disease of the nasal mucosa, caused by an interaction between genetic and environmental factors. As evidence suggests that some genetic variants may increase susceptibility to both AR and asthma, the objective of this study was to identify asthma susceptibility variants associated with AR in the Chinese population.', 'A cohort of 402 individuals with physician-diagnosed AR and 416 healthy controls were recruited from the Han Chinese population in Beijing. DNA was extracted from the peripheral blood and a total of 12 single-nucleotide polymorphisms (SNPs) shown to be associated with asthma in Japanese subjects were selected for genotyping using the SequenomMassARRAY technology platform.', 'Analysis of frequency differences of allele between the AR patients and control subjects showed that the C allele of rs204993 in the pre-B-cell leukemia homeobox 2 (PBX2) gene from the 6p21.3 locus was significantly associated with AR (p = 0.0006, pcorrected = 0.0340). Genotype analysis further confirmed the difference in distribution of this variant between AR patients and controls in the both the dominant (pT/C+C/C vs T/T = 7.37\u00d710(-5) ) and co-dominant (pT/C vs T/T = 1.98 \u00d7 10(-4) , pC/C vs T/T = 0.004) models.",
            "output": [
                "Does variant of PBX2 gene in the 6p21.3 asthma susceptibility locus is associate with allergic rhinitis in Chinese subjects?"
            ]
        },
        {
            "id": "task847-bfa8deb441e846e88e0dcf3223dd6a3e",
            "input": "The study focuses on the analysis of the possible relationship between a common NYD-SP18 (rs6971091, G>A) gene polymorphism and weight loss after lifestyle intervention (combined dietary intake and physical activity) in overweight/obese females.', 'We genotyped 139 unrelated non-diabetic Czech females (49.5 \u00b1 13.3 years, average BMI at baseline 32.2 \u00b1 4.6 kg/m\u00b2. Biochemical and anthropometrical measurements were performed before and after ten weeks of lifestyle intervention.",
            "output": [
                "Do body Composition Changes in Adult Females after Lifestyle Intervention Are Influenced by the NYD-SP18 Variant?"
            ]
        },
        {
            "id": "task847-bc3b5ca8fce14afaa937fc6e23ad6e28",
            "input": "A history of preeclampsia is an independent risk factor for cardiac events and stroke. Changes in vasculature structure that contribute to these associations are not well understood.', 'The aim of this study was to quantify coronary artery calcification (CAC), a known risk factor for cardiac events, in a prospective cohort of women with and without histories of preeclampsia.', 'Women without prior cardiovascular events (40 with and 40 without histories of preeclampsia, matched for parity and age at index birth) were recruited from a large population-based cohort of women who were residents of Olmsted County, Minnesota, and who delivered from 1976 through 1982. Computed tomography was performed to measure CAC in Agatston units. All pregnancy histories and covariates were confirmed by review of the medical records. Current clinical variables were assessed at the time of imaging. Differences between women with and without histories of preeclampsia were examined using \u03c7(2) tests and tests; CAC, in particular, was compared as a categorical and ordinal variable, with a \u03c7(2) test and with Wilcoxon 2-sample tests and ordinal logistic regression, as appropriate.', 'Mean age (SD) at imaging was 59.5 (\u00b14.6) years. Systolic and diastolic blood pressures, hyperlipidemia, and current diabetes status did not differ between women with and without histories of preeclampsia. However, the frequencies of having a current clinical diagnosis of hypertension (60% vs 20%, P < .001) and higher body mass index in kg/m(2) (expressed as median [25th-75th percentile], 29.8 [25.9-33.7] vs 25.3 [23.1-32.0], P = .023) were both greater in the women with histories of preeclampsia compared to those without. The frequency of a CAC score >50 Agatston units was also greater in the preeclampsia group (23% vs 0%, P = .001). Compared to women without preeclampsia, the odds of having a higher CAC score was 3.54 (confidence interval [CI], 1.39-9.02) times greater in women with prior preeclampsia without adjustment, and 2.61 (CI, 0.95-7.14) times greater after adjustment for current hypertension. After adjustment for body mass index alone, the odds of having a higher CAC based on a history of preeclampsia remained significant at 3.20 (CI, 1.21-8.49).",
            "output": [
                "Is a history of preeclampsia associated with a risk for coronary artery calcification 3 decades later?"
            ]
        },
        {
            "id": "task847-25401f7dd4f5493da9c9d061e4f12c46",
            "input": "The efficacy of fractional photothermolysis and topical use of calcineurin inhibitors as treatments of idiopathic guttate hypomelanosis (IGH) have been reported. Data on combination treatments are lacking.', 'To evaluate the efficacy and safety of 1550-nm ytterbium/erbium fiber laser combined with 0.1% tacrolimus ointment as a treatment of IGH.', 'In each patient with IGH, two lesions were assigned as a treatment group, whilst two lesions on another side were chosen as control. Four treatments by fractional 1550-nm ytterbium/erbium fiber laser were delivered every four weeks combined with a twice daily topical application of 0.1% tacrolimus ointment. Lesional skin color was measured by colorimeter. Digital and dermoscopic digital photographs were taken and evaluated by three dermatologists.', \"A total of 120 lesions were treated. Combination treatment normalized the relative lightness index of IGH which reached statistical significant compared with the control at week 12, after three sessions of laser treatment (p\\u2009=\\u20090.026). Physicians' assessment score revealed that 91.67% of the lesions on treatment side showed an improvement. Swelling and redness were the most common side effects which spontaneously resolved.",
            "output": [
                "Is combination of non-ablative fractional photothermolysis and 0.1 % tacrolimus ointment efficacious for treating idiopathic guttate hypomelanosis?"
            ]
        },
        {
            "id": "task847-a8f7621674d04c39b2913dc9c9898151",
            "input": "To assess the beneficial effects of silver foam dressing on the healing of wounds with ulcers and infection control of burn patients.', 'Eighty-four second-degree burn patients were selected and divided into a study group and a control group (n=42). After disinfection and cleaning, wound beds of the study group were covered with silver-containing soft-silicone foam dressing, and wound surfaces of the control group were wiped with 1% silver sulfadiazine cream (60 g/100 cm(2)). The two groups were checked weekly to observe wound healing progress and adverse reactions of the skin around wounds. Wound secretions were collected and subjected to bacterial culture. Related indices were recorded and quantified.', 'Thirty seven cases of the study group (88.1%) and 36 cases of the control group (85.7%) recovered to normal, and 3 (7.1%) and 2 cases (4.8%) in the two groups failed to recover. The recovery rates of the two groups were similar (P>0.05), but unrecovered patients in the study group had significantly higher proportions of repaired wounds (P<0.05). Wounds of the study group were healed significantly more rapidly than those of the control group (22.3\u00b13.1 vs. 25.1\u00b14.4, P<0.05). The study group had significantly higher proportions of repaired wounds from Day 7 to Day 21 (P<0.05), but the difference became less obvious with extended time to Day 28. The bacterial culture-positive (exceeding 10(5) organisms per gram of tissue) rates of both groups significantly reduced after treatment (Day 7 for the study group and Day 14 for the control group), and the rate of the study group was significantly lower at last (P<0.05). The study and control groups were observed 134 and 149 person-times respectively, with the normal wound-surrounding skin rates of 96.3% (129/134) and 88.6% (132/149) (P>0.05 except for on Day 14). Except for on Day 28, the study group had significantly lower pain scores than those of the control group (P<0.05), especially on Day 7 and Day 14 (P<0.01). From Day 7 to Day 28, the study group was significantly less prone to burning sensation than the control group (P<0.05), but both groups felt anxious during dressing change (P>0.05). Dressing of the study group was changed significantly more easily (P<0.05), but the fixing outcomes were similar (P>0.05).",
            "output": [
                "Do beneficial effects of silver foam dressing on healing of wounds with ulcers and infection control of burn patients?"
            ]
        },
        {
            "id": "task847-1fd062b03ec4496b8a729f90bfe09f92",
            "input": "Extended hospitalization for school-aged cancer patients increases their risk of social marginalization. School-aged children mature through peer-interaction, but healthcare providers fail to incorporate this in rehabilitation efforts. The RESPECT study offers classmates to cancer patients to become ambassadors during hospital stays. This study explores classmate decision-making patterns about ambassadorship.', 'An open-ended question was prospectively and consecutively provided to classmates (N\\u2009=\\u2009221) (and parents) of 10 children diagnosed with cancer in 2014 and enrolled in the RESPECT study. Statements were analysed using thematic content analysis.', 'Of 221 classmates, 140 responded (63%). Of these, 81 applied for ambassadorship (median 8/patient), 58 declined, one was undecided. Nine forms were incomplete; leaving 131 in total that revealed 303 statements for analysis. Five major themes emerged: existing friendship (132/303 statements), personal resources (academic, emotional and social) (107/303), attitudes towards the ambassadorship (34/303), hospital environment (18/303) and logistics (12/303). Of the classmates with pre-existing friendships, 77% applied for ambassadorship and 80% with a surplus of personal resources applied. These were predominant predictors for ambassadorship application. Classmate motives were condensed into four archetypes: pre-existing friendship with a surplus of resources (100% applied), non-friend classmates with a surplus of resources (63% applied), pre-existing friendship with limited resources (22% applied) and non-friend classmates with limited resources (0% applied).",
            "output": [
                "Are in sickness and in health : classmates highly motivated to provide in-hospital support during childhood cancer therapy?"
            ]
        },
        {
            "id": "task847-7d63c518f7d541d986658eebcce4655d",
            "input": "Fight or flight heart rate (HR) increases depend on protein kinase A (PKA)- and calmodulin kinase II (CaMKII)-mediated enhancement of Ca(2+) uptake and release from sarcoplasmic reticulum (SR) in sinoatrial nodal cells (SANC). However, the impact of specific PKA and CaMKII phosphorylation sites on HR is unknown.', 'We systematically evaluated validated PKA and CaMKII target sites on phospholamban and the ryanodine receptor using genetically modified mice. We found that knockin alanine replacement of ryanodine receptor PKA (S2808) or CaMKII (S2814) target sites failed to affect HR responses to isoproterenol or spontaneous activity in vivo or in SANC. Similarly, selective mutation of phospholamban amino acids critical for enhancing SR Ca(2+) uptake by PKA (S16) or CaMKII (T17) to alanines did not affect HR in vivo or in SANC. In contrast, CaMKII inhibition by expression of AC3-I has been shown to slow SANC rate responses to isoproterenol and decrease SR Ca(2+) content. Phospholamban deficiency rescued SR Ca(2+) content and SANC rate responses to isoproterenol in mice with AC3-I expression, suggesting that CaMKII affects HR by modulation of SR Ca(2+) content. Consistent with this, mice expressing a superinhibitory phospholamban mutant had low SR Ca(2+) content and slow HR in vivo and in SANC.",
            "output": [
                "Does a Single Protein Kinase A or Calmodulin Kinase II Site Control the Cardiac Pacemaker Ca2+ Clock?"
            ]
        },
        {
            "id": "task847-3fec96eb2d9947419427cff424da254f",
            "input": "Old compared with young adults walk with reduced ankle and increased hip mechanical output. We examined the idea that age, leg strength, or both are related to the age-related changes in mechanical output during gait.', 'Healthy young (n = 32, age 21.5 years) and old adults (n = 32, age 76.8 years) participated in biomechanical gait analyses at 1.5 m/s and were also measured for maximal leg strength.', 'Analysis 1 confirmed previous data as old compared with young adults walked with 50 % more hip positive work and 18 % less ankle positive work. Analysis 2 showed that leg strength did not affect gait kinetics in groups of subjects with similar ages. In a weak young and a strong old group, Analysis 3 showed that old adults still walked with 23 % greater hip positive work. The group by joint interaction in Analysis 4 was suggestive of an even greater reliance on hip and less reliance on ankle work in weak compared with strong old adults.",
            "output": [
                "Do age and muscle strength mediate the age-related biomechanical plasticity of gait?"
            ]
        },
        {
            "id": "task847-b552f5b04af44f5494208bc8fc2f6b08",
            "input": "The objectives of this study are to identify oral commensal species which can inhibit the growth of the main periodontopathogens, to determine the antimicrobial substances involved in these inhibitory activities and to evaluate the influence of environmental factors on the magnitude of these inhibitions.', 'The spotting technique was used to quantify the capacity of 13 commensal species to inhibit the growth of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia. By altering experimental conditions (distance between spots and size of spots and concentration of commensal and pathogen) as well as environmental factors (inoculation sequence, oxygen and nutrition availability) the influence of these factors was evaluated. Additionally, the mechanism of inhibition was elucidated by performing inhibition experiments in the presence of peroxidase, trypsin and pepsin and by evaluating acid production.', 'Streptococcus sanguinis, Streptococcus cristatus, Streptococcus gordonii, Streptococcus parasanguinis, Streptococcus mitis and Streptococcus oralis significantly inhibit the growth of all pathogens. The volume of the spots and concentration of the commensal have a significant positive correlation with the amount of inhibition whereas distance between the spots and concentration of the pathogen reduced the amount of inhibition. Inhibition is only observed when the commensal species are inoculated 24h before the pathogen and is more pronounced under aerobic conditions. Hydrogen peroxide production by the commensal is the main mechanism of inhibition.",
            "output": [
                "Are antimicrobial effects of commensal oral species regulated by environmental factors?"
            ]
        },
        {
            "id": "task847-cacaf08d0c28436cbcb4a80f1c33fc8d",
            "input": "To describe the novel use of a chorioretinal biopsy technique to confirm the microbiological diagnosis of endogenous Escherichia coli (E. coli) endophthalmitis, when other investigations have been proven nondiagnostic.', 'Case report of an 82-year-old white man with endogenous endophthalmitis without a clearly identifiable source of infection.', 'After systemic cultures and multiple aqueous and vitreous samples were unable to identify a causative organism, chorioretinal biopsy of a subretinal abscess was used to confirm the microbiological diagnosis. This ensured appropriate ophthalmic and systemic treatment of infection.",
            "output": [
                "Do cHORIORETINAL BIOPSY FOR THE DIAGNOSIS OF ENDOGENOUS ENDOPHTHALMITIS DUE TO ESCHERICHIA COLI?"
            ]
        },
        {
            "id": "task847-c221bb62b3294458941edfc7a10ba39e",
            "input": "Most previous glaucoma studies with resting-state fMRI have focused on the neuronal activity in the individual structure of the brain, yet ignored the functional communication of anatomically separated structures. The purpose of this study is to investigate the efficiency of the functional communication change or not in glaucoma patients.', 'We applied the resting-state fMRI data to construct the connectivity network of 25 normal controls and 25 age-gender-matched primary open angle glaucoma patients. Graph theoretical analysis was performed to assess brain network pattern differences between the two groups.', \"No significant differences of the global network measures were found between the two groups. However, the local measures were radically reorganized in glaucoma patients. Comparing with the hub regions in normal controls' network, we found that six hub regions disappeared and nine hub regions appeared in the network of patients. In addition, the betweenness centralities of two altered hub regions, right fusiform gyrus and right lingual gyrus, were significantly correlated with the visual field mean deviation.",
            "output": [
                "Does graph theoretical analysis reveal the reorganization of the brain network pattern in primary open angle glaucoma patients?"
            ]
        },
        {
            "id": "task847-ced735515ac0481587defc250721e8cc",
            "input": "Cancer stem cell-tumor microenvironment ecosystem is proposed to drive tumor heterogeneity. Tumor-infiltrating lymphocytes (TILs) in breast cancer ecosystem were demonstrated to indicate better prognosis and benefit from chemotherapy. This study sought to detect the association between breast cancer stem cells and TILs.', '92 patients with breast cancer were enrolled. Matched cancerous and paracancerous tissues were assembled in a tissue microarray and immunohistochemistry was employed to test expression of breast cancer stem cells (BCSCs) markers. TILs counts were estimated with global hematoxylin-eosin staining. The association between TILs and BCSCs phenotypes was analysed by multivariate analysis.', 'Although it was unable to find direct significant association between BCSCs phenotypes and TILs, the BCSCs phenotype with CD44(+)CD24(-)ALDH1A1(+)EpCAM(+)CD49f(+) was proved to be associated with worse DFS and OS (P=0.037 and 0.001). This result was confirmed by cox proportional-hazards regression model (for DFS and OS respectively, HR=2.438 and 3.383, P=0.019 [95%CI 1.418-3.457] and 0.025 [95%CI 1.162-9.843]). Additionally, in results of TILs, plasma cell-predominant breast cancer (PPBC) was unexpectedly found to indicate worse OS and HR was 2.686 (P=0.038 [95%CI 1.582-3.789]).",
            "output": [
                "Do breast cancer stem cells phenotype and plasma cell-predominant breast cancer independently indicate poor survival?"
            ]
        },
        {
            "id": "task847-76886c9db36d4512ac8f0b8a30615677",
            "input": "Delayed gastric emptying (DGE) is a common complication of pancreaticoduodenectomy. We determined the efficiency of a new reconstruction technique, designed to preserve motilin-secreting cells and maximize the utility of their receptors, in reducing the incidence of DGE after pancreaticoduodenectomy.', 'From April 2005 to September 2014, 217 consecutive patients underwent pancreaticoduodenectomy at our institution. Nine patients who underwent total pancreatectomy were excluded. We compared outcomes between patients who underwent pancreaticoduodenectomy with resection of the pyloric ring followed by proximal Roux-en-y gastrojejunal anastomosis (group I, n\\u2009=\\u200990) and patients who underwent standard pancreaticoduodenectomy with the orthotopic reconstruction technique (group II, n\\u2009=\\u2009118).', 'Overall and clinically relevant rates of DGE were significantly lower in group I than in group II (10 and 2.2\\xa0% vs. 57 and 24\\xa0%, respectively; p\\u2009<\\u20090.05). Length of hospital stay as a result of DGE was shorter in group I than in group II. In univariate analysis, older age, comorbidities, ASA grade 4, operative time, preoperative diabetes, standard reconstruction technique, and postoperative complications were significant risk factors for DGE. In multivariate analysis, older age, standard technique, and postoperative complications were independent risk factors for DGE.",
            "output": [
                "Does proximal Roux-en-y Gastrojejunal Anastomosis with Pyloric Ring Resection improve Gastric Emptying After Pancreaticoduodenectomy?"
            ]
        },
        {
            "id": "task847-e0cae0de2f5942f89c6ec60a96314cd5",
            "input": "Atp13a2 (Park9) gene encodes a transmembrane lysosomal P5-type ATPase (ATP13A2), and its missense or truncation mutations leads to lysosomal dysfunction and consequently results in neuronal death in the pathogenesis of Parkinson's disease (PD). Nevertheless, the roles of ATP13A2 in the biological features of astrocytes, especially in the regulation of PD-related neuroinflammation, have not been investigated.\", 'We cultured primary neurons and astrocytes from mouse midbrain to investigate the mechanisms for astrocyte ATP13A2-regulated lysosomal function and neuroinflammation following 1-methyl-4-phenylpyridinium (MPP(+) ) treatment.', 'We found that astrocytes expressed considerable levels of ATP13A2 and deficiency of ATP13A2 in astrocyte-induced intense inflammation, which exacerbated dopaminergic neuron damage after exposure to MPP(+) . Notably, lack of ATP13A2 increased lysosomal membrane permeabilization and cathepsin B release, which in turn exacerbated activation of nod-like receptor protein 3 (NLRP3) inflammasome to produce excess IL-1\u03b2 from astrocytes. Furthermore, overexpression of ATP13A2 reversed MPP(+) -induced cathepsin B release and NLRP3 inflammasome activation in astrocytes.",
            "output": [
                "Does atp13a2 Deficiency aggravate Astrocyte-Mediated Neuroinflammation via NLRP3 Inflammasome Activation?"
            ]
        },
        {
            "id": "task847-2c66465a80a3483985f86dd36c908bbe",
            "input": "The existence of health disparities in military populations has become an important topic of research. However, to our knowledge, this is the first study to examine health disparities, as related to access to care and health status, among active duty soldiers and their families. Specifically, the purpose of this analysis was to evaluate whether health disparities exist in access to care and health outcomes of patient satisfaction, physical health status, and mental health status according to race, gender, and sponsor rank in the population of active duty soldiers and their family members.', 'In this cross-sectional study, active duty army soldiers and family members were recruited from either one particular army health clinic where they received their health care or from an adjacent shopping center frequented by eligible participants. Data were collected using validated measures to assess concepts of access to care and health status. Statistical analysis, including one-way analysis of variance (ANOVA) was performed to investigate differences in study outcome measures across four key demographic subgroups: race, gender, sponsor rank, and component (active soldier or family member).', 'A total of 200 participants completed the study questionnaires. The sample consisted of 45.5 % soldiers and 54.5 % family members, with 88.5 % reporting a sponsor rank in the category of junior or senior enlisted rank. Mean scores for access to care did not differ significantly for the groups race/ethnicity (p\\u2009=\\u20090.53), gender (p\\u2009=\\u20090.14), and sponsor rank (p\\u2009=\\u20090.10). Furthermore, no significant differences were observed whether respondents were active soldiers or their family members (p\\u2009=\\u20090.36). Similarly, there were no statistically significant subgroup (race/ethnicity, gender, sponsor rank, or component) differences in mean patient satisfaction, physical health, and mental health scores.",
            "output": [
                "Do the Military Health Care System May Have the Potential to Prevent Health Care Disparities?"
            ]
        },
        {
            "id": "task847-4fe5bd78d32a4d01b686ced888ed610a",
            "input": "Although CT scans provide great medical benefits, concerns have been raised about the magnitude of possible associated cancer risk, particularly in children who are more sensitive to radiation than adults. Unnecessary high doses during CT examinations can also be delivered to children, if the scan parameters are not adjusted for patient age and size. We conducted the first survey to directly assess the trends in CT scan parameters and doses for paediatric CT scans performed in Great Britain between 1978 and 2008.', 'We retrieved 1073 CT film sets from 36 hospitals. The patients were 0-19 years old, and CT scans were conducted between 1978 and 2008. We extracted scan parameters from each film including tube current-time product [milliampere seconds (mAs)], tube potential [peak kilovoltage (kVp)] and manufacturer and model of the CT scanner. We estimated the mean mAs for head and trunk (chest and abdomen/pelvis) scans, according to patient age (0-4, 5-9, 10-14 and 15-19 years) and scan year (<1990, 1990-1994, 1995-1999 and \u22652000), and then derived the volumetric CT dose index and estimated organ doses.', 'For head CT scans, mean mAs decreased by about 47% on average from before 1990 to after 2000, with the decrease starting around 1990. The mean mAs for head CTs did not vary with age before 1990, whereas slightly lower mAs values were used for younger patients after 1990. Similar declines in mAs were observed for trunk CTs: a 46% decline on an average from before 1990 to after 2000. Although mean mAs for trunk CTs did not vary with age before 1990, the value varied markedly by age, from 63\\u2009mAs for age 0-4 years compared with 315\\u2009mAs for those aged >15 years after 2000. No material changes in kVp were found. Estimated brain-absorbed dose from head CT scans decreased from 62\\u2009mGy before 1990 to approximately 30\\u2009mGy after 2000. For chest CT scans, the lung dose to children aged 0-4 years decreased from 28\\u2009mGy before 1990 to 4\\u2009mGy after 2000.",
            "output": [
                "Does reduction in radiation doses from paediatric CT scan in Great Britain?"
            ]
        },
        {
            "id": "task847-d4d3652a37d64b21a9ba85b2de5e23a5",
            "input": "Within the context of microalgal lipid production for biofuels and bulk chemical applications, specialized higher throughput devices for small scale parallelized cultivation are expected to boost the time efficiency of phototrophic bioprocess development. However, the increasing number of possible experiments is directly coupled to the demand for lipid quantification protocols that enable reliably measuring large sets of samples within short time and that can deal with the reduced sample volume typically generated at screening scale. To meet these demands, a dye based assay was established using a liquid handling robot to provide reproducible high throughput quantification of lipids with minimized hands-on-time.', \"Lipid production was monitored using the fluorescent dye Nile red with dimethyl sulfoxide as solvent facilitating dye permeation. The staining kinetics of cells at different concentrations and physiological states were investigated to successfully down-scale the assay to 96 well microtiter plates. Gravimetric calibration against a well-established extractive protocol enabled absolute quantification of intracellular lipids improving precision from \u00b18 to \u00b12 % on average. Implementation into an automated liquid handling platform allows for measuring up to 48 samples within 6.5 h, reducing hands-on-time to a third compared to manual operation. Moreover, it was shown that automation enhances accuracy and precision compared to manual preparation. It was revealed that established protocols relying on optical density or cell number for biomass adjustion prior to staining may suffer from errors due to significant changes of the cells' optical and physiological properties during cultivation. Alternatively, the biovolume was used as a measure for biomass concentration so that errors from morphological changes can be excluded.",
            "output": [
                "Does automation of a Nile red staining assay enable high throughput quantification of microalgal lipid production?"
            ]
        },
        {
            "id": "task847-e3c22da2998d44389495d80af50c4f44",
            "input": "Ulcerative colitis (UC) is a chronic inflammatory intestinal disease. It is necessary to find out new effective drugs for UC. In our study epicatechin extracted from grape seed by our institute for the first time could treat UC effectively. Then anti-UC mechanisms of epicatechin were elucidated in vivo and in vitro.', 'Dextran sulfate sodium (DSS)-induced acute UC mice model was used to evaluate the activity of epicatechin and its properties against UC. Then its anti-inflammatory and antioxidant effects were evaluated as follows: the concentrations of TNF-\u03b1 and IL-6 in the colon supernatants were determined by ELISA. NO and MPO were assayed by Griess method and commercial kit respectively. NF-\u03baB were determined by NF-\u03baB-Dependent Reporter Gene Expression Assay and Western Blotting respectively. Antioxidant factors such as SOD, MDA, GSH-Px and CAT were also measured in colon tissues and cell supernatant stimulated by LPS respectively.', 'In C57BL/6J mice model with DSS-induced UC, epicatechin was able to decrease the disease activity index and colon macroscopic damage index scores, reduce body weight loss, and significantly relieve colon contracture and crypt damage. TNF-\u03b1, IL-6, NO, MPO and MDA were reduced in the mice administered epicatechin, whereas antioxidant enzymes showed increased activity in epicatechin-treated mice and cell line respectively. Furthermore, inhibition effect on NF-\u03baB activation by epicatechin were demonstrated in vivo and in vitro.",
            "output": [
                "Is the protective effect of epicatechin on experimental ulcerative colitis in mice mediated by increasing antioxidation and by the inhibition of NF-\u03baB pathway?"
            ]
        },
        {
            "id": "task847-5f9ebf760d9244e18114cb14ce8162b8",
            "input": "Middle third clavicular fracture is effectively treated by conservative means. Previous studies showed that comminution and displacement of clavicular fractures might affect fracture healing. However, the clavicle horizontally aligns in the shoulder girdle and has different biomechanics from vertical weight-bearing bones. Therefore, this study was conducted with the hypothesis that comminution has no effect in worsening fracture healing and union configurations in conservatively treated middle third clavicular fractures.', 'One hundred ninety-eight middle third clavicular fractures treated by conservative means were reviewed and divided into 2 groups. Group 1, simple fractures, included 97 patients. Group 2, comminuted fractures, included 101 patients. Patient demographic data, initial fracture deformities, and union configurations such as angulation, overlying, and displacement were measured. Union rate and union complications such as delayed nonunion were evaluated. Data were analyzed for statistically significant differences (p<0.05).', 'Initial deformities of Group 1 and Group 2 were 11.94\u00b0\u00b19.59\u00b0 and 9.40\u00b0\u00b18.57\u00b0 angulation, 12.24\u00b112.96 and 11.76\u00b110.06 mm of overlying, and 13.31\u00b18.63 and 13.72\u00b17.42 mm of displacement, respectively, and exhibited no significant differences (p>0.05). Union rate and union complications of Group 1 were 74/97 (76.29%) and 23/97 (23.71%), respectively. For Group 2, the rates were 82/101 (81.19%) and 19/101 (18.81%), respectively. Union configuration of Group 1 and Group 2 were 13.76\u00b0\u00b110.63\u00b0 and 12.80\u00b0\u00b18.65\u00b0 angulation, 11.93\u00b110.75 and 11.52\u00b19.38 mm of overlying, and 9.79\u00b18.33 and 10.74\u00b16.68 mm of displacement, respectively, and showed no significant differences between the groups.",
            "output": [
                "Does comminution play no role in worsening fracture healing of conservatively treated middle third clavicular fractures?"
            ]
        },
        {
            "id": "task847-60377524a1bd42eda3c9ce8f41ff0127",
            "input": "To evaluate the effects of obesity-associated inflammation on influenza vaccine responses.', 'In young and elderly individuals, both lean and with obesity, antibody responses to influenza vaccination were measured.', 'A decrease in in vivo vaccine responses, circulating switched memory, and transitional B cells and an increase in pro-inflammatory late/exhausted memory B cells were found. In vitro B cell function was measured by activation-induced cytidine deaminase and E47, markers of optimal antibody responses. Moreover, IL-6 production was increased, whereas IL-10 production was decreased in cultures of B cells from individuals with obesity. Markers of immune activation (TNF-\u03b1, TLR4, micro-RNAs) in unstimulated B cells were also found increased and were negatively correlated with B cell function. In order to reveal potential mechanisms, we stimulated B cells from lean individuals in vitro with leptin, the adipokine increased in obesity. Leptin increased phospho-STAT3, crucial for TNF-\u03b1 production, and decreased phospho-AMPK, the energy sensing enzyme upstream of phospho-p38 MAPK and E47. Leptin-induced phospho-STAT3 and phospho-AMPK levels were similar to those in B cells from individuals with obesity.",
            "output": [
                "Does obesity decrease B cell responses in young and elderly individuals?"
            ]
        },
        {
            "id": "task847-48b4d1025e7544be9f27c27cfe583ed9",
            "input": "The Arp2/3 complex is required for cell migration and invasion. The Arp2/3 complex and its activators, such as the WAVE complex, are deregulated in diverse cancers. Here we investigate the expression of Arpin, the Arp2/3 inhibitory protein that antagonises the WAVE complex.', 'We used qRT-PCR and reverse phase protein arrays in a patient cohort with known clinical parameters and outcome, immunofluorescence in breast biopsy cryosections and breast cancer cell lines.', 'Arpin was downregulated at the mRNA and protein levels in mammary carcinoma cells. Arpin mRNA downregulation was associated with poor metastasis-free survival (MFS) on univariate analysis (P=0.022). High expression of the NCKAP1 gene that encodes a WAVE complex subunit was also associated with poor MFS on univariate analysis (P=0.0037) and was mutually exclusive with Arpin low. Arpin low or NCKAP1 high was an independent prognosis factor on multivariate analysis (P=0.0012) and was strongly associated with poor MFS (P=0.000064).",
            "output": [
                "Is arpin downregulation in breast cancer associated with poor prognosis?"
            ]
        },
        {
            "id": "task847-abb1c05724fd447c9ffaf80500705b1f",
            "input": "The role of the adipokine, resistin in mediating increases in aortic stiffness is uncertain. We aimed to determine independent relations between circulating resistin concentrations and aortic pulse wave velocity (PWV) and wave reflection in a community-based sample with a high prevalence of untreated hypertension and obesity.', 'Plasma resistin, adiponectin, and C-reactive protein concentrations (ELISA); carotid-femoral (aortic) PWV and the aortic reflected wave index (applanation tonometry and SphygmoCor software) were determined in 683 randomly selected participants of African ancestry from SOWETO, South Africa who had never received antihypertensive therapy.', 'Resistin concentrations were not independently associated with office or 24-h (n\\u200a=\\u200a492) blood pressure (BP). In a stepwise regression model with BMI included in the model, age (P\\u200a<\\u200a0.0001), mean arterial pressure (P\\u200a<\\u200a0.0001), plasma resistin concentrations (P\\u200a<\\u200a0.005), female sex (P\\u200a=\\u200a0.01), and creatinine concentrations (P\\u200a<\\u200a0.01) contributed independently to variations in PWV. Independent relations between resistin concentrations and PWV persisted with further adjustments for C-reactive protein concentrations (P\\u200a<\\u200a0.005), and the homeostasis model of insulin resistance (P\\u200a<\\u200a0.02). Similar relations were noted with waist circumference rather than BMI in the model. Resistin concentrations were not independently associated with aortic reflected wave index or aortic BP.",
            "output": [
                "Are circulating resistin concentrations independently associated with aortic pulse wave velocity in a community sample?"
            ]
        },
        {
            "id": "task847-606b2f6c5ed94d29aca823d2f02bc679",
            "input": "Sodium thiosulfate (STS) is an industrial chemical which has also been approved for the treatment of certain rare medical conditions. These include cyanide poisoning and calciphylaxis in hemodialysis patients with end-stage kidney disease. Here, we investigated the anti-inflammatory activity of STS in our glial-mediated neuroinflammatory model.', 'Firstly, we measured glutathione (GSH) and hydrogen sulfide (H2S, SH(-)) levels in glial cells after treatment with sodium hydrosulfide (NaSH) or STS. We also measured released levels of tumor necrosis factor-\u03b1 (TNF\u03b1) and interleukin-6 (IL-6) from them. We used two cell viability assays, MTT and lactate dehydrogenase (LDH) release assays, to investigate glial-mediated neurotoxicity and anti-inflammatory effects of NaSH or STS. We also employed Western blot to examine activation of intracellular inflammatory pathways.', 'We found that STS increases H2S and GSH expression in human microglia and astrocytes. When human microglia and astrocytes are activated by lipopolysaccharide (LPS)/interferon-\u03b3 (IFN\u03b3) or IFN\u03b3, they release materials that are toxic to differentiated SH-SY5Y cells. When the glial cells were treated with NaSH or STS, there was a significant enhancement of neuroprotection. The effect was concentration-dependent and incubation time-dependent. Such treatment reduced the release of TNF\u03b1 and IL-6 and also attenuated activation of P38 MAPK and NF\u03baB proteins. The compounds tested were not harmful when applied directly to all the cell types.",
            "output": [
                "Does sodium thiosulfate attenuate glial-mediated neuroinflammation in degenerative neurological diseases?"
            ]
        },
        {
            "id": "task847-d6795e9e0b924177be1be2c8a2b0ff4d",
            "input": "Potent antitumor responses can be induced through cytokine immunotherapy. Interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are among the most effective cytokines to induce tumor-specific systemic immune responses and can act synergistically. To overcome the limitations of combined use of these two cytokines, we have constructed an IL2-GMCSF fusion protein and characterized its antitumor effects in this study.', 'The expression of IL-2 receptor and GM-CSF receptor of cell lines were detected with quantitative real-time PCR. On this basis, the bioactivities of IL2-GMCSF, especially effects on DC2.4 cells were assayed. Another function of IL2-GMCSF-bridge two types of cells-was assessed by cell contact counting and cytotoxicity assays. The anti-tumor activity in vivo of IL2-GMCSF was evaluated in the melanoma model. The statistical significance among treatment groups were determined by One-Way ANOVA.', 'The fusion protein IL2-GMCSF maintained the activities of IL-2 and GM-CSF, and could significantly promote DC2.4 cell activities, including phagocytosis, proliferation and cytokine secretion. In addition to the inherent cytokine activity, IL2-GMCSF bridges direct cell-cell interactions and enhances splenocyte killing efficacy against multiple tumor cell lines in vitro. Co-injection of IL2-GMCSF and inactivated B16F10 mouse melanoma cells induced complete immunoprotective responses in about 30 % of mice.",
            "output": [
                "Does fusion cytokine IL-2-GMCSF enhance anticancer immune responses through promoting cell-cell interactions?"
            ]
        },
        {
            "id": "task847-075f2b1a13d84788a1b6e7162ae2b2bd",
            "input": "The purpose of this study is to examine the effect of insurance coverage on stage of presentation, treatment, and survival of head and neck cancer (HNC).', 'A retrospective study was conducted using the Surveillance, Epidemiology, and End Results (SEER) program to identify patients diagnosed with HNC. The primary variable of interest was insurance analyzed as a dichotomous variable: Patients were considered uninsured if they were classified as \"uninsured\" by SEER, whereas patients were considered insured if they were defined by SEER as \"any Medicaid,\" \"insured,\" or \"insured/no specifics.\" The outcomes of interest were cancer stage at presentation (M0 vs M1), receipt of definitive treatment, and HNC-specific mortality (HNCSM). Multivariable logistic regression modeled the association between insurance status and stage at presentation, as well as between insurance status and receipt of definitive treatment, whereas HNCSM was modeled using Fine and Gray competing risks. Sensitivity logistic regression analysis was used to determine whether observed interactions remained significant by insurance type (privately insured, Medicaid, and uninsured).', 'Patients without medical insurance were more likely to present with metastatic cancer (adjusted odds ratio, 1.60; P < .001), were more likely to not receive definitive treatment (adjusted odds ratio, 1.64; P < .001), and had a higher risk of HNCSM (adjusted hazard ratio, 1.20; P\\xa0= .002). Sensitivity analyses showed that when results were stratified by insurance type, significant interactions remained for uninsured patients and patients with Medicaid.",
            "output": [
                "Does health Insurance affect Head and Neck Cancer Treatment Patterns and Outcomes?"
            ]
        },
        {
            "id": "task847-40c52305b8474c8d969ba583564ba83c",
            "input": "To evaluate the presence of a spontaneous pulsatile release of kisspeptin and whether it is temporally coupled to LH pulses.', 'Experimental study.', 'Academic medical center.', 'Thirty young healthy eumenorrheic women aged 20-37\\xa0years were included in the study group. All subjects were white women admitted to the Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.', 'Kisspeptin, FSH, LH, E2, PRL, and insulin were evaluated in all subjects at baseline.', 'All women underwent a pulsatility study measuring LH and kisspeptin plasma concentrations to assess the spontaneous episodic secretion of both hormones, sampling every 10\\xa0minutes for 2\\xa0hours from 9:00 to 11:00 a.m. for a total of 12 blood samples. Detection and specific concordance (SC) algorithms were used to detect pulses and their concordance.', 'A significant endogenous secretory pattern was demonstrated for both LH and kisspeptin over the 2-hour duration of the study (2.4 \u00b1 0.1 peaks/2\\xa0h). The computation of the SC index showed for the first time that kisspeptin and LH are cosecreted and temporally coupled at time \"0,\" and their peaks occur at the same point in time.",
            "output": [
                "Is spontaneous endogenous pulsatile release of kisspeptin temporally coupled with luteinizing hormone in healthy women?"
            ]
        },
        {
            "id": "task847-5bef756a14284d53a8bf97d3feb830e6",
            "input": "Adiponectin has been shown to possess potent anti-oxidative properties in various experimental conditions. However, its anti-oxidative effects and underlying mechanisms have not been reported in liver cells. Herein, we investigated the effects of globular adiponectin (gAcrp) on LPS-stimulated reactive oxygen species (ROS) production and its mechanisms underlying in human hepatic cells (HepG2).', 'Intracellular ROS production was determined by fluorescence of 5-chloromethyl-2,7-dichlorodihydrofluorescein diacetate (CM-H2DCFDA). NADPH oxidase-dependent ROS formation was determined by lucigenin-derived chemiluminescence. Messenger RNA expression level of target genes was determined by quantitative RT-PCR and protein expression was measured by Western blot analysis.', 'LPS-induced increase in ROS production was prevented by pretreatment with gAcrp in HepG2 cells. Furthermore, gAcrp treatment suppressed LPS-induced activation of NADPH oxidase and increase in mRNA and protein expression of Nox-4. We also found that adiponectin increased expression of FoxO3A and HO-1 and ablation of either of these genes partially restored suppression of LPS-induced ROS production and NADPH oxidase activation by gAcrp, indicating the vital role of FoxO3A and HO-1 signaling in the inhibition of ROS production and NADPH oxidase activation by gAcrp.",
            "output": [
                "Does globular adiponectin attenuate LPS-induced reactive oxygen species production in HepG2 cells via FoxO3A and HO-1 signaling?"
            ]
        },
        {
            "id": "task847-88b7c24fc5324941bd557b268dcc9489",
            "input": "Almost all the past CSWT studies show the beneficial effects on CAD patients in a maximum duration of 1-year follow-up. The aim of this study was to evaluate the actual CSWT effects in 6 years follow-up period.', 'The subjects were selected exclusively on the basis of inclusion criteria. The total number of patients was 52, out of which control group (n = 11) and the shock wave group (SW group, n = 41) was selected.', 'The wall motion, MPI, nitrate dosage, NYHA classification, SAQ scores, CCS grading, 6 MWT were markedly improved in the long-term (6 years) follow-up for SW group than the control group.",
            "output": [
                "Does cardiac shock wave therapy show better outcomes in the coronary artery disease patients in a long term?"
            ]
        },
        {
            "id": "task847-0654cf6d68aa4fcd8dbb2f43c8cee036",
            "input": "Previous studies have demonstrated that microRNA-21 (miR-21) is involved in the pathogenesis of myocardium infarction and cardiac fibrosis; the present study aimed to investigate its potential role in the diagnosis of acute myocardium infarction (AMI).', 'A cohort of patients with AMI and angina pectoris (AP) were studied, plasma miR-21 level was determined by Realtime-PCR.', 'We found that the plasma miR-21 level was significantly elevated in patients with AMI compared with those with AP or healthy people. Further studies demonstrated the correlation of miR-21 and several traditional markers such as creatine kinase (CK), creatine kinase-MB (CK-MB) and troponin I (cTnI) in study subjects. Finally, receiver-operator characteristic curve (ROC) analysis showed that miR-21 has similar diagnostic ability compared with CK, CK-MB and cTnI.",
            "output": [
                "Is plasma microRNA-21 a potential diagnostic biomarker of acute myocardial infarction?"
            ]
        },
        {
            "id": "task847-0a3edf856488471fb9867569fb101709",
            "input": "Multiple rib fractures cause significant pain and potential for chest wall instability. Despite an emerging trend of surgical management of flail chest injuries, there are no studies examining the effect of rib fracture fixation on respiratory function.', 'Using a novel full thorax human cadaveric breathing model, we sought to explore the effect of flail chest injury and subsequent rib fracture fixation on respiratory outcomes.', 'We used five fresh human cadavers to generate negative breathing models in the left thorax to mimic physiologic respiration. Inspiratory volumes and peak flows were measured using a flow meter for all three chest wall states: intact chest, left-sided flail chest (segmental fractures of ribs 3 - 7), and post-fracture open reduction and internal fixation (ORIF) of the chest wall with a pre-contoured rib specific plate fixation system.', 'A wide variation in the mean inspiratory volumes and peak flows were measured between specimens; however, the effect of a flail chest wall and the subsequent internal fixation of the unstable rib fractures was consistent across all samples. Compared to the intact chest wall, the inspiratory volume decreased by 40 \u00b1 19% in the flail chest model (P = 0.04). Open reduction and internal fixation of the flail chest returned the inspiratory volume to 130 \u00b1 71% of the intact chest volumes (P = 0.68). A similar 35 \u00b1 19% decrease in peak flows was seen in the flail chest (P = 0.007) and this returned to 125 \u00b1 71% of the intact chest following ORIF (P = 0.62).",
            "output": [
                "Does rib Fracture Fixation restore Inspiratory Volume and Peak Flow in a Full Thorax Human Cadaveric Breathing Model?"
            ]
        },
        {
            "id": "task847-bc1684cc65f148bda7f3d65ee93782dd",
            "input": "In colorectal cancer (CRC), as in most of other malignancies, heat shock proteins (HSPs) are overexpressed and are associated with apoptosis, cancer cell proliferation, differentiation, invasion, and metastasis. HSP70 is one of the HSPs and has a promising future in cancer studies for both diagnostic and therapeutic applications. In this study, we tried to evaluate the serum levels of HSP70 in CRC patients, and to evaluate its predictive value of detecting CRC.', 'This prospective study was consisted of 33 patients diagnosed with CRC and 31 healthy subjects who were matched for age. Enzyme-linked immunosorbent assays (ELISA) were used to evaluate the serum levels of HSP70 in patients with CRC and in the healthy control group. A cut-off value for HSP70 was also determined using receiver operating characteristic (ROC) curve analysis.', 'Patients with CRC had significantly higher HSP70 concentrations compared with the control group (4.52 \u00b1 1.83 vs 1.22 \u00b1 0.48 ng/ml, p=0.001), the cut-off value was \u22652.25 ng/ml (95% CI 0.993-1.003, p<0.001). The sensitivity and specificity of elevated serum HSP70 in the CRC group were 96.77 and 96.96%, respectively. Also, HSP70 levels were significantly higher with rectal disease localization (p=0.01).",
            "output": [
                "Is heat shock protein 70 a useful marker for predicting colorectal cancer?"
            ]
        },
        {
            "id": "task847-0405bcf9c4304f28a24161347acfecae",
            "input": "Cervical carcinoma is the second most common malignancy in females and most of the cases are found in developing countries. The objectives of the present study were (a): to demonstrate the antiproliferative and apoptotic effects of Achillea falcata (A.falcata) extract in human cervical cancer cells (HeLa), and (b): to study the effect of the extract on cellular morphology, cell cycle phase distribution and mitochondrial membrane potential.', 'MTT assay was used to evaluate the anticancer effect of the extract on HeLa cells. Phase contrast, fluorescence microscopy and transmission electron microscopy (TEM) were used to investigate the morphological changes in these cancer cells after extract treatment. Flow cytometry was used to evaluate the effects of the extract on cell cycle and mitochondrial membrane potential.', 'The results revealed that A. falcata extract led to a significant antiproliferative effect in HeLa cancer cells. The extract induced cellular shrinkage, chromatin condensation and appearance of apoptotic bodies which are the hallmarks of cellular apoptosis. TEM results showed that extract-treated cells had nuclear membrane which was hemispherical and the nuclear chromatin was concentrated and bundled on the inner border of karyotheca. The endoplasmic reticulum also became enlarged in the inner segment. The extract also induced G2/M phase cell cycle arrest along with loss of mitochondrial membrane potential.",
            "output": [
                "Are antiproliferative and apoptotic effects of the ethanolic herbal extract of Achillea falcata in human cervical cancer cells mediated via cell cycle arrest and mitochondrial membrane potential loss?"
            ]
        },
        {
            "id": "task847-e996c0725f1f43198072c958ababd6da",
            "input": "Patients undergoing chemoradiation for head and neck squamous cell carcinoma (HNSCC) are predisposed to unplanned hospitalizations.', 'To assess the factors associated with prolonged hospitalization and its impact on patient outcomes.', 'We assessed the outcomes of patients hospitalized for \u22655 days or <5 days in 251 patients with advanced HNSCC who were undergoing radiotherapy during 2000-2012.', 'Patients who had been hospitalized for \u22655 days were more likely to be admitted for infection, acute renal failure, and/or dehydration. We found no other patient, tumor, or treatment characteristics associated with prolonged hospitalizations. Hospitalizations of \u22655 days were associated with a higher incidence of delays in radiotherapy (RT; odds ratio [OR], 2.49; 95% confidence index [CI], 1.09-5.69; \ud835\udc43 = .03) and worse performance status after RT (OR, 5.76; 95% CI, 1.85-18.38; \ud835\udc43 = .003). On multivariate analysis, hospitalization of \u22655 days predicted for worse local-regional control (hazard ratio [HR], 1.85; 95% CI, 1.08-3.17; \ud835\udc43 = .03) and time to treatment failure (HR, 1.64; 95% CI, 1.03-2.61; \ud835\udc43 = .04), and performance status after RT predicted for worse local-regional control, time to treatment failure, progression-free survival, and overall survival.",
            "output": [
                "Do hospitalizations of more than 5 days predict for worse outcomes after radiotherapy for head and neck cancer?"
            ]
        },
        {
            "id": "task847-b6acade512e146a0b287eaa8e000b03a",
            "input": "The purpose of this study was to evaluate the impact of a modified sagittal split osteotomy (SSO) surgical technique on the incidence of persisting inferior border defects. The secondary aim was to identify risk factors associated with the development of these complications.', 'The patient charts and radiographs of 276 consecutive patients who underwent bilateral SSO, performed by a single surgeon in 2 different centers from July 2012 to September 2014, were retrospectively examined. The predictor variable was length of advancement. The outcome variable was the presence or absence of an inferior border defect. Other variables included age and side of the jaw. In all cases the same surgical technique was used. All statistical analyses were performed using SAS software, version 9.4 (SAS Institute, Cary, NC).', 'The analysis included 408 operation sites in 204 patients (132 female and 72 male patients; median age, 22\\xa0years; age range, 13 to 66\\xa0years). In 5.1% of operation sites an osseous defect at the lower border of the mandible was observed. Age at the time of surgery (P < .0001) and length of advancement (P\\xa0= .0111) were identified as risk factors for the development of a persisting osseous defect at the inferior border of the osteotomy gap after SSO.",
            "output": [
                "Does modified Mandibular Inferior Border Sagittal Split Osteotomy reduce Postoperative Risk for Developing Inferior Border Defects?"
            ]
        },
        {
            "id": "task847-916ca207f240451c8906c73e15f64d3d",
            "input": "L1-cell adhesion molecule (L1CAM) was previously reported to carry a poor prognosis in Stage I, low-risk endometrial cancer (EC). We evaluated the role of L1CAM among all stages and histologies in ECs in The Cancer Genome Atlas (TCGA).', 'Clinical information and RNA-Seq expression data were derived from TCGA uterine cancer cohort. Associations between L1CAM expression and clinical factors were tested with linear and logistic regression. Differences in survival between \"high\" and \"low\" expression groups (defined by median expression) of L1CAM were compared using Cox regression analysis, with p-values calculated via log-rank test. Kaplan-Meier curves were tested with the log-rank test.', 'Patient characteristics of 545 primary tumors with RNA-Seq gene expression data were analyzed. Median age was 64years (range 31-90). Stage I, II, III, and IV comprised 62%, 10%, 23%, and 5%, respectively. 75% were endometrioid; 21% serous. Grade 1, 2, and 3 comprised 18%, 22%, and 60%, respectively. Median follow-up was 23.0months. High L1CAM expression was associated with advanced stage (OR 3.2), high grade (OR=6.8), serous histology (OR=16.3), positive cytology (OR=3.5), positive pelvic (OR=21.8) and para-aortic lymph nodes (OR=10.3) (all p\u22640.001). High L1CAM was associated with a median overall survival (OS) of 107months, versus not reached for low L1-expressing ECs (HR=3.46, CI 1.97-6.07, p<0.001). On multivariate analysis, L1CAM expression remained an independent prognostic variable in predicting OS in EC.",
            "output": [
                "Is l1CAM an independent predictor of poor survival in endometrial cancer - An analysis of The Cancer Genome Atlas ( TCGA )?"
            ]
        },
        {
            "id": "task847-9504671dc12a4eaeb7a4808370164605",
            "input": "To train novices to perform an abbreviated duplex lower limb ultrasound scan using simulation training and assess real-world skills transference.', 'Novices undertook 3 days of simulation training. Their progress was assessed using the Duplex Ultrasound Objective Structured Assessment of Technical Skills (DUOSATS) for simulation and Cumulative Imaging Score (CIS). A final assessment day was held to assess DUOSATS for simulation and real patient scanning, CIS, cumulative diagnostic accuracy, and sections A and B of the Society of Vascular Technology examination. MSc students in vascular ultrasound were also assessed for comparison.', 'A total of 17 novices and 7 MSc students with 3-month training participated. Novices improved DUOSATS for simulation scores between days 1, 3, and 4: 18 (17-19) vs 27 (25-28) vs 30 (28-32), (median [interquartile range], p < 0.001). Novices improved in CIS between days 1 and 3: 10 (10-13) vs 21 (19-21), p < 0.001, with a decline on day 4: 15.3 (11.3-18.3), p < 0.001. On the final assessment day, there were no significant differences between novices and MSc students in: DUOSATS for simulation scores (30 [28-32] vs 31 [6-31.5], p = 0.85); DUOSATS for patient assessment (31 [28.7-33.7] vs 26.7 [24.5-35.7], p = 0.41); CIS (15.3 [11.3-18.7] vs 20.7 [12.3-22.2], p = 0.2), respectively. However, novices performed better in section B of the Society of Vascular Technology examination compared with MSc students (72.9% vs 54.3%, p < 0.001). Novices also demonstrated a higher diagnostic accuracy when compared with MSc students (65.7% of arterial segments correctly assessed vs 47.6%, respectively [p = 0.044]).",
            "output": [
                "Does intensive Simulation Training in Lower Limb Arterial Duplex Scanning lead to Skills Transfer in Real-World Scenario?"
            ]
        },
        {
            "id": "task847-105478e46c2742e2ba5388cc3e8cc3bd",
            "input": "To investigate the effectiveness, related knowledge, attitudes, and practices of hand hygiene (HH) among dental students with different levels of clinical experience.', \"This was a cross-sectional analytical study. Bacterial samples on the participants' hands were obtained using a swab technique before and after handwashing, for oral surgical procedures. After culturing, the colony-forming units were counted. Self-reported questionnaires reflecting the knowledge, attitudes, and practices related to HH were completed by the participants.\", 'This study was performed in a primary oral health care institution, Faculty of Dentistry, Chulalongkorn University (Bangkok, Thailand). Bacterial samples and self-reported questionnaires were collected in the Department of Oral and Maxillofacial Surgery. Bacterial culture was performed in the Department of Microbiology.', 'The 120 participants comprised first, second, third-year clinical training students (CTs), and postgraduate dental students (PGs) (32, 34, 30, and 24 participants, respectively).', \"More than 99% of the bacteria were eliminated from the participants' hands after handwashing. Significantly higher numbers of bacteria were recovered from the hands of the PGs compared with those of the CTs, and the hands of the third-year CTs compared with those of the first-year CTs (p < 0.001), after HH. The first-year CTs had the highest attitude scores, whereas the PGs had the lowest practice scores. The knowledge scores were similar in all groups.",
            "output": [
                "Do dental Student Hand Hygiene Decreased With Increased Clinical Experience?"
            ]
        },
        {
            "id": "task847-94947e188f3649e59dfb26462c440c7a",
            "input": "Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings.', 'To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined.', 'Plasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-na\u00efve neuroasymptomatic subjects with low blood CD4(+) T cells.",
            "output": [
                "Is plasma Concentration of the Neurofilament Light Protein ( NFL ) a Biomarker of CNS Injury in HIV Infection : A Cross-Sectional Study?"
            ]
        },
        {
            "id": "task847-9926cd160a5340309f71548067bf5f9e",
            "input": "Essentials The platelet thrombin receptor, PAR4, is an emerging anti-thrombotic drug target. We examined the anti-platelet & anti-thrombotic effects of PAR4 inhibition in human blood. PAR4 inhibition impaired platelet procoagulant activity in isolated cells and during thrombosis. Our study shows PAR4 is required for platelet procoagulant function & thrombosis in human blood.",
            "output": [
                "Does inhibition of protease-activated receptor 4 impair platelet procoagulant activity during thrombus formation in human blood?"
            ]
        },
        {
            "id": "task847-ee58801c641b4cbd971a5a61b0475b97",
            "input": "To identify the presence or absence of 38 postpartum hemorrhage preparedness elements in hospitals in New Jersey and Georgia as a component of the Postpartum Hemorrhage Project of the Association of Women's Health, Obstetric and Neonatal Nurses.\", 'Quality improvement baseline assessment survey.', 'Hospitals (N = 95) in New Jersey and Georgia.', \"Key informants were clinicians who were members of their hospitals' obstetric teams and were recognized as knowledgeable about their hospitals' postpartum hemorrhage policies.\", \"An electronic survey was sent by e-mail to each identified hospital's key informant.\", 'The mean number of elements present was 23.1 (SD = 5.2; range = 12-34). Volume of births, students, magnet status, and other hospital characteristics did not predict preparedness. None of the hospitals had all of the 38 preparedness elements available. Less than 50% of the hospitals had massive hemorrhage protocols, performed risk assessments and drills, or measured blood loss. For every 10% increase in the total percentage of African American women who gave birth, there was a decrease of one preparedness element.",
            "output": [
                "Do postpartum Hemorrhage Preparedness Elements Vary Among Hospitals in New Jersey and Georgia?"
            ]
        },
        {
            "id": "task847-3d798f356e7a44a5aee2a4238a06bed0",
            "input": "Wilson's disease (WD) is a genetic disorder of copper metabolism causing dysfunctions of various organs, mostly the liver and brain. If untreated, WD is fatal, but early treatment results in a good prognosis, although the long-term neurological outcome has not yet been clarified. To address this issue, we evaluated the neurological status of early-treated WD patients without overt nervous system impairment using neurophysiological, neuropsychological and neuroimaging procedures at least 10 years after treatment onset.\", 'Thirty-eight WD patients (18 females, aged 24.47 \u00b1 7.50 years), who received an early diagnosis (in presymptomatic or mild/moderate liver disease stages without neurological involvement) and prompt treatment, were clinically evaluated with the Global Assessment Scale. Presentation was hepatic in 36 subjects (95%), while 2 patients (5%) were presymptomatic. A neurophysiological study was performed to explore the central motor conduction time of the upper and lower limbs, and motor cortex excitability using single pulses and paired-pulse transcranial magnetic stimulation. Neuroimages were obtained with brain magnetic resonance scans. Cognitive abilities, and psychiatric and behavioral disturbances were evaluated with neuropsychological tests.', 'Patients were undergoing treatment with penicillamine (7 patients) or zinc salts (31 patients) with good adherence. They did not present any neurological signs at clinical evaluation or at specific scale of impairment, the mean Global Assessment Scale score was 0.3 \u00b1 0.7. Magnetic resonance imaging, transcranial magnetic stimulation studies and neuropsychological/neuropsychiatric assessment ruled out subclinical involvement.",
            "output": [
                "Does subclinical neurological involvement develop if Wilson 's disease is treated early?"
            ]
        },
        {
            "id": "task847-79bfbd0e09654b9980c80b785ffd1e31",
            "input": "Angiotensin-converting enzyme (ACE) inhibitors improve prognosis in patients with post-myocardial infarction (MI) related cardiac dysfunction. Resveratrol is a polyphenol that has been reported to be beneficial in hypertension, ischemic heart disease, and cardiotoxicity in preclinical studies. Accordingly, we investigated the comparative and combinatorial efficacy of resveratrol and perindopril (ACE inhibitor) treatment on MI-related cardiac remodeling and contractile dysfunction.', 'Left anterior descending artery-ligated and sham-operated male Sprague-Dawley rats were gavaged with vehicle, resveratrol, perindopril, and combination of resveratrol+perindopril (2.5 mg/kg bodyweight/day) for 8 weeks (starting immediately after acute MI). Echocardiography was performed to assess cardiac structure and function at baseline and 8 weeks.', 'At 8 weeks, vehicle-MI rats had a significantly lower left ventricular ejection fraction (LVEF) and increased LV dilatation compared to vehicle-sham rats. MI rats treated with resveratrol, perindopril and a combination of both had significantly improved LVEF and reduced LV dilatation. Vehicle-treated MI rats also had increased level of lipid peroxidation product- malondialdehyde (MDA), proinflammatory protein- tumor necrosis factor-alpha (TNF-\u03b1) and cardiac fibrosis marker- collagen and decreased enzymatic activity of superoxide dismutase and catalase compared to vehicle-sham rats. Resveratrol, perindopril and combination of both significantly prevented the /ed to determine systolic functional parameter increase in MDA, TNF-\u03b1 and collagen and improved the activity of superoxide dismutase and catalase in MI rats compared to vehicle-MI rats.",
            "output": [
                "Is resveratrol equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats?"
            ]
        },
        {
            "id": "task847-68435dfef5e34258910bb2967587312f",
            "input": "It has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats.', 'Forty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope.', 'Lipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation.",
            "output": [
                "Does vitamin A supplementation modify the antioxidant system in rats?"
            ]
        },
        {
            "id": "task847-bfe4f43285b24f22bc8cd25815e5cdc5",
            "input": "Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined.', 'In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans.', 'Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae.",
            "output": [
                "Does oligonol promote anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway?"
            ]
        },
        {
            "id": "task847-92c3d5c8f2d94791b203f1f5fbe33e7a",
            "input": "Early safe discharge is paramount for the success of ERAS following colorectal cancer resections. Anastomotic leakage (AL) has high morbidity, particularly if the patient has been discharged to the community.', 'To evaluate whether C-reactive protein (CRP) and procalcitonin (PCT) can predict AL before early discharge.', 'Fifty-five consecutive patients undergoing open and robotic colorectal cancer resections were included. C-reactive protein and PCT were measured pre-operatively, 8 h after incision, and on the first and third postoperative day. Thirty-day readmissions, re-operations and mortality were recorded.', 'Twenty-nine patients underwent robotic and the remainder open (n = 26) resections. Five patients had AL. The mean CRP and PCT increased on postoperative day 1 (POD 1) and POD 3 in all patients. On POD 3, mean CRP was 114 mg/l in non-AL patients and 321 mg/l in AL patients (p = 0.0001). Mean PCT on POD 3 was 0.56 ng/ml in the non-AL group and 10.4 ng/ml in AL patients (p = 0.017). On analysis of ROC and AUC curves, the cut-off for CRP on POD 3 was 245.64 mg/l, with 100% sensitivity and 98% specificity for AL. The cut-off for PCT on POD 3 was 3.83 ng/ml, with 75% sensitivity and 100% specificity for AL.",
            "output": [
                "Do c-reactive protein and procalcitonin predict anastomotic leaks following colorectal cancer resections - a prospective study?"
            ]
        },
        {
            "id": "task847-6a3727c5ec44497d802f9e12d75190ff",
            "input": "To study the association between bed occupancy in psychiatric wards and rate of adverse incidents (AIs) including aggressive behavior and falls.', \"This is a retrospective study analyzing bed occupancy and AIs' data in 4 closed wards in a state psychiatric hospital in Israel over a 20-month period. Ward-level daily records were extracted from the hospital's electronic admission-discharge and AI registries, creating a log of 609 days for each of the 4 wards. Relationships between gross and net bed occupancy and AIs rate were calculated, in general and for each ward and type of incidents.\", 'Average gross occupancy was 106\u00b114.8% and net occupancy was 96.4\u00b115.6%. Gross occupancy >100% was recorded in 51% of days. Net occupancy was higher on days with at least 1 incident than on no-incident days (98.6\u00b114.8% vs. 95.7\u00b115.7%, P<0.0001). AIs occurred in 18.6% of days in the lowest occupancy quadrant (up to 85% occupancy), compared with 26.7% of days in the highest occupancy quadrant (106% and above). Moreover, aggressive behavior-type incidents were significantly lower in the lowest occupancy quadrant days compared with the highest occupancy quadrant (8.3% vs. 14.1%, P<0.01). Evidence of a dose-response effect of bed occupancy on AIs rate was found.",
            "output": [
                "Is overcrowding in Psychiatric Wards Associated With Increased Risk of Adverse Incidents?"
            ]
        },
        {
            "id": "task847-523f52ad012a4b8a84e27aa08a250ff8",
            "input": "The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp.', 'Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months.', 'Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p\\xa0<\\xa0.001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p\\xa0=\\xa0.001, and 5/25 vs. 32/44, respectively, p\\xa0<\\xa0.001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p\\xa0=\\xa0.007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p\\xa0<\\xa0.001). No differences in median AAA sac diameter shrinkage were detected between the two groups at 6-12 months (p\\xa0=\\xa0.42 and p\\xa0=\\xa0.58, respectively). Freedom from ELIIp related and embolization related re-interventions was 100% in both groups, at 6 and 12 months.",
            "output": [
                "Does selective Intra-procedural AAA sac Embolization During EVAR reduce the Rate of Type II Endoleak?"
            ]
        },
        {
            "id": "task847-be8cbe9cfd5a4dce9c87d92bc5a47311",
            "input": "Heart type fatty acid binding protein (H-FABP) is a small protein and released into the circulation when myocardial damage has occurred. Previous studies have demonstrated that H-FABP is closely associated with cardiac and some endocrinologic disorders including prediabetes, metabolic syndrome, and acromegaly. Hyperthyroism is a well-known disorder associated with cardiovascular diseases. We aimed to investigate the effect of hyperthyrodism on H-FABP levels.', 'Forty six patients with hyperthyroidism with no known history of coronary artery disease and 40 healthy controls are involved in the study. Serum H-FABP levels are measured using sandwich enzyme-linked immunosorbent assay.', 'There was no significant difference between serum H-FABP levels of patients with hyperthyroidism and controls (871\u00b166 pg/mL, and 816\u00b166 pg/mL, respectively P=0.56). There was no significant correlation between H-FABP, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in patients and controls.",
            "output": [
                "Are serum heart type fatty acid binding protein levels changed in hyperthyroidism?"
            ]
        },
        {
            "id": "task847-ed0749f220954f0d9275c8b28d73b4e1",
            "input": "Nociceptin/orphanin FQ (N/OFQ) receptor (NOP) agonists produce anxiolytic-like effects in rodents while antagonists promote antidepressant-like effects. The aim of this study was to investigate the effect on anxiety and depression of NOP receptor partial agonists such as the peptides [F/G]N/OFQ(1-13)NH2 and UFP-113 and the non-peptide AT-090.', 'In\\xa0vitro AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 were tested for their ability to promote NOP/G-protein and NOP/\u03b2-arrestin 2 interaction, using a bioluminescence resonance energy transfer assay. In\\xa0vivo, they were tested in mice in the elevated plus maze (EPM) and in the forced swim (FST) tests. NOP partial agonists effects were systematically compared to those of full agonists (N/OFQ and Ro 65-6570) and antagonists (UFP-101 and SB-612111).', 'In\\xa0vitro, AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 promoted NOP/G protein interaction, with maximal effects lower than those evoked by N/OFQ and Ro 65-6570. AT-090 behaved as a NOP partial agonist also in inducing \u03b2-arrestin 2 recruitment, while UFP-113 and [F/G]N/OFQ(1-13)NH2 were inactive in this assay. In\\xa0vivo, AT-090 induced anxiolytic-like effects in the EPM but was inactive in the FST. Opposite results were obtained with UFP-113 and [F/G]N/OFQ(1-13)NH2.",
            "output": [
                "Does beta-arrestin 2 rather than G protein efficacy determine the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands?"
            ]
        },
        {
            "id": "task847-bf14857dff494999ae1ae9aa35d27a2a",
            "input": "The need for suitable selective cultivation media for the isolation of Bifidobacterium spp. continues to be a real concern in the field of intestinal microbiology. Isolation of bifidobacteria from human and animal faecal samples using selective agar plating may be problematic especially in samples with increased clostridial counts than bifidobacterial counts. Due to the absence of anticlostridial agents in existing selective media, clostridia can displace bifidobacteria resulting in incorrect estimation of their counts. Therefore, we supplemented the existing selective medium 'modified Wilkins Chalgren agar with mupirocin' (MWM) with 90\\xa0mg\\xa0l(-1) of 8-hydroxyquinoline (8HQ), which was recently proved to act selectively against clostridia. The newly composed 'modified Wilkins-Chalgren agar with 8HQ' (MWMQ) was tested on pure bifidobacterial and clostridial strains, their mixtures, and using faecal samples of mammalian origin; its selectivity was evaluated by genus-specific identification of isolates. The results demonstrated that the presence of 8HQ in this agar eliminated the growth of nonbifidobacterial strains on MWMQ compared to that on MWM, whereas the recovery of bifidobacterial counts was at satisfactory levels. In conclusion, MWMQ could be recommended for bifidobacterial isolation from human and animal faeces especially when bifidobacteria are not numerically dominant and there are chances of clostridial contamination.",
            "output": [
                "Does anticlostridial agent 8-hydroxyquinoline improve the isolation of faecal bifidobacteria on modified Wilkins-Chalgren agar with mupirocin?"
            ]
        },
        {
            "id": "task847-923888c856dd49d49e28588e168212b1",
            "input": "Static magnetic fields (SMF) have been widely used in research, medicine and industry. Since zinc and copper play an important role in biological systems, we studied the effects of the subchronic continuous SMF exposure on their distribution in murine tissues.', 'For 30 days, mice were exposed to inhomogeneous, vertical, downward or upward oriented SMF of 1\\u2009mT averaged intensity with spatial gradient in vertical direction.', 'SMF decreased the amount of copper and zinc in liver. In brain, zinc levels were increased and copper levels were decreased. In spleen, zinc content was reduced, while copper amount remained unchanged.",
            "output": [
                "Does subchronic exposure to static magnetic field differently affect zinc and copper content in murine organs?"
            ]
        },
        {
            "id": "task847-78980b10ad634d89b7b1e20480055f8c",
            "input": "Treatment abandonment (TxA) is a primary cause of therapy failure in children with cancer in low-/middle-income countries. We explored the absence of social support network (SSN), among other predictive factors, and TxA in children with cancer in Cali, Colombia.', \"In this prospective cohort study, we included children diagnosed with cancer at a public university hospital. A social worker and a psychologist administered semistructured questionnaires to patients' caregivers. We extracted information from the questionnaires about social, economic, and psychological conditions of the patients' families. Outcomes were death, relapse, and TxA. Failure either to start or to continue the planned course of curative treatment for 4 weeks or more was defined as TxA. We identified events with Cali's childhood cancer outcomes surveillance system (VIGICANCER). We adjusted the hazard ratios (HRs) for potential confounders using multivariate Cox regression analyses.\", 'Among 188 patients diagnosed from January 2011 to June 2013, 99 interviews were conducted. Median age was 5 years old (range: 0.3, 14.9), 53% were male, 17% were of Colombian-Indian ethnicity, and 68% lived in rural areas. The 2-year cumulative incidence of TxA was 21% (95% confidence interval [CI]: 13, 35) and the annual proportion was 14%. The adjusted HR for the absence of SSN was 4.9 (95% CI: 1.6, 15.3).",
            "output": [
                "Is caregivers ' Self-Reported Absence of Social Support Networks Related to Treatment Abandonment in Children With Cancer?"
            ]
        },
        {
            "id": "task847-f5b2d826851048c09cb140b80b154ca0",
            "input": "Inbreeding increases homozygosity and exposes deleterious recessive alleles, generally decreasing the fitness of inbred individuals. Interestingly, males and females are usually affected differently by inbreeding, though the more vulnerable sex depends on the species and trait measured.', 'We used the soil-dwelling nematode Caenorhabditis remanei to examine sex-specific inbreeding depression across nine lineages, five levels of inbreeding, and hundreds of thousands of progeny. Female nematodes consistently suffered greater fitness losses than their male counterparts, especially at high levels of inbreeding.",
            "output": [
                "Do intrinsic differences between males and females determine sex-specific consequences of inbreeding?"
            ]
        },
        {
            "id": "task847-320bcde1db284607a11f5bd6e5d9e96e",
            "input": "Although the \"right not to know\" is well established in international regulations, it has been heavily debated. Ubiquitous results from extended exome and genome analysis have challenged the right not to know. American College of Medical Genetics and Genomics (ACMG) Recommendations urge to inform about incidental findings that pretend to be accurate and actionable. However, ample clinical cases raise the question whether these criteria are met. Many incidental findings are of uncertain significance (IFUS). The eager to feedback information appears to enter the field of IFUS and thereby threaten the right not to know. This makes it imperative to investigate the arguments for and against a right not to know for IFUS.",
            "output": [
                "Is incidental findings of uncertain significance : To know or not to know -- that the question?"
            ]
        },
        {
            "id": "task847-eac6a476b3914e7784052567022be7f7",
            "input": "We examined the associations between HbA1c levels and various atherosclerotic vascular parameters among adults without diabetes from the general population.', 'A total of 6500 community-dwelling adults, who were free of type 2 diabetes and \u226550 years of age, were included. High-resolution B-mode ultrasound was used to evaluate carotid artery structure, including intima-media thickness (IMT), plaque, and luminal diameter. Brachial-ankle pulse wave velocity (baPWV), which is a useful indicator of systemic arterial stiffness, was determined using an automatic waveform analysis device.', 'No significant associations were observed between HbA1c, carotid IMT, plaque, or luminal diameter in a fully adjusted model. However, the odds ratio (95% confidence interval) for high baPWV (defined as the highest quartile) increased by 1.43 (1.19-1.71) per 1% HbA1c increase after adjusting for conventional risk factors in a multivariate logistic regression analysis. In addition, HbA1c was independently associated with baPWV in a multivariate linear regression analysis.",
            "output": [
                "Is hbA1c significantly associated with arterial stiffness but not with carotid atherosclerosis in a community-based population without type 2 diabetes : The Dong-gu study?"
            ]
        },
        {
            "id": "task847-52ac513019534d7a927fdbe3de148cc1",
            "input": "The goal of elective orthopedic surgery is to return patients to their expected level of activity without an increased incidence of postoperative complications. The first step is identifying patient and/or surgical characteristics responsible for these complications.', 'This study sought to identify predictors of a step-up in medical care after non-ambulatory elective orthopedic surgery.', 'At a single specialty orthopedic hospital, we identified all in-hospital postoperative patients who were transferred to a higher level of medical care ((PACU) post-anesthesia care unit). The characteristics of both transferred and non-transferred patients were compared. A model was built which incorporated predictors of return to a higher level of care.', 'During a 1-year period, 155 of 7967 patients (1.95%) required transfer to the PACU within 5\\xa0days of surgery. Cardiac complications were the major reason for transfer (50.3%), followed by pulmonary (11.0%) and neurological complications (9.7%). Patients who returned to the PACU were older, had more Exlihauser comorbidities, and had obstructive sleep apnea (OSA). In a model adjusting for all patient characteristics: age, American Society of Anesthesiologists (ASA) status, congestive heart failure (CHF), the Charlson comorbidity index and OSA predicted return to the PACU.",
            "output": [
                "Is the Need for a Step-up in Postoperative Medical Care Predictable in Orthopedic Patients Undergoing Elective Surgery?"
            ]
        },
        {
            "id": "task847-4228982848f242e584b090d8288bbbb3",
            "input": "Although most humeral nonunions are successfully treated with a single procedure, some humeral nonunions are more difficult to heal and require multiple procedures. Current literature does not provide evidence describing how the prognosis for surgical repair in patients who develop humeral diaphyseal nonunions may be affected by initial operative versus nonoperative treatment.', 'The purpose of this study was to assess whether operative versus nonoperative treatment of acute humeral shaft fractures impacts outcome of subsequent repairs of humeral nonunions (NU) including the need for additional surgery and a comparison of pain relief (Visual Analogue Scale for pain) and functional outcome (Short Musculoskeletal Functional Assessment).', 'Thirty-four patients with humeral shaft nonunion were evaluated of which 15 patients had been treated operatively (OF), and 19 patients had been treated nonoperatively (NO) for their initial humerus shaft fracture. All patients underwent plating with autogenous bone graft or allograft \u00b1 bone morphogenic protein (BMP) 2 or 7 as their final NU repair surgery prior to healing. We compared functional outcome and pain for both cohorts and determined risk factors for requiring more than 1 nonunion repair surgery.', 'The mean time of final follow-up was 14.7\\u2009\u00b1\\u200910.4\\xa0months. Thirty-three of 34 NUs (97.1%) healed. Patients who underwent OF of their original fracture were more likely to require more than 1 NU repair surgery (66.7 vs. 0%, p\\u2009<\\u20090.01). Of the 15 patients who underwent initial OF, 33.0% required 1 NU surgery, 33.0% required 2 NU surgeries, and 33.0% required 3 NU surgeries. Patients who underwent initial OF were more likely to require >6\\xa0months to achieve union (40.0 vs. 10.5%, p\\u2009=\\u20090.04). At final follow-up, there was no difference in functional outcome or pain scores. Initial OF was the only independent predictor of needing more than 1 NU repair surgery (OR 70.1 CI 2.8-1762.3) to achieve healing.",
            "output": [
                "Does initial Surgical Treatment of Humeral Shaft Fracture predict Difficulty Healing when Humeral Shaft Nonunion Occurs?"
            ]
        },
        {
            "id": "task847-f6cc2e7cd43c4ca9859d39aa9c8e72e6",
            "input": "Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia.', 'A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically-triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase.",
            "output": [
                "Do early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve?"
            ]
        },
        {
            "id": "task847-b7ca4736942b42ecb82d3af5cfa17a5c",
            "input": "A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC).', 'Quantitative real-time PCR was used to detect the expression miR-361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR-361-5p in vivo.', 'miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice.",
            "output": [
                "Does microRNA-361-5p inhibit Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma?"
            ]
        },
        {
            "id": "task847-272b6833671d462a9f41d4d29880ffdc",
            "input": "Preclinical studies generated the hypothesis that older stored red blood cells (RBCs) can increase transfusion risks. To examine the most updated and complete clinical evidence and compare results between two trial designs, we assessed both observational studies and randomized controlled trials (RCTs) studying the effect of RBC storage age on mortality.', 'Five databases were searched through December 2014 for studies comparing mortality using transfused RBCs having longer and shorter storage times.', 'Analysis of six RCTs found no significant differences in survival comparing current practice (average storage age of 2 to 3\\xa0weeks) to transfusion of 1- to 10-day-old RBCs (OR 0\u00b791, 95% CI 0\u00b777-1\u00b707). RBC storage age was lower in RCTs vs. observational studies (P\\xa0=\\xa00\u00b701). The 31 observational studies found an increased risk of death (OR 1\u00b713, 95% CI 1\u00b703-1\u00b724) (P\\xa0=\\xa00\u00b701) with increasing age of RBCs, a different mortality effect than RCTs (P\\xa0=\\xa00\u00b702).",
            "output": [
                "Does transfusion of recently donated ( fresh ) red blood cells ( RBCs ) improve survival in comparison with current practice , while safety of the oldest stored units is yet to be established : a meta-analysis?"
            ]
        },
        {
            "id": "task847-89603e78adda4a40a719270fe1985f41",
            "input": "In routine practice, major depressive disorder (MDD) with psychotic features often goes under-recognized and undertreated. Previous research has specified several demographic and clinical differences in MDD patients with psychotic features compared with those without psychosis in routine outpatient practice, but there is little systematic research in modern routine hospital settings.', 'We conducted a retrospective electronic medical records chart review of 1,314 patients diagnosed with MDD who were admitted consecutively to a major psychiatric hospital over a 1-year period. We examined the prevalence of psychotic features in the sample and investigated the differences in demographic variables, clinical characteristics, and medication use patterns among patients with and without psychosis.', 'The prevalence of psychotic features was 13.2% in the current hospital sample. Patients with psychotic depression were more likely to be older, male, a member of a racial/ethnic minority, and have more medical comorbidities and certain Axis I disorders compared with nonpsychotic patients. In addition, patients with psychotic depression were more likely to be prescribed antipsychotics and hypnotics before admission.",
            "output": [
                "Do clinical characteristics and medication use patterns among hospitalized patients admitted with psychotic vs nonpsychotic major depressive disorder?"
            ]
        },
        {
            "id": "task847-fdba1550f9664620aa2e5861b5925659",
            "input": "Previous studies with BIT225 (N-carbamimidoyl-5-(1-methyl-1H-pyrazol-4-yl)-2-naphthamide) have demonstrated a unique antiviral activity that blocks the release of HIV-1 from monocyte-derived macrophages (MDM). Antagonising the ion channel formed by HIV-1 Vpu, BIT225 preferentially targets de novo intracellular virus produced in 'virus-containing compartments' of MDM. In primary infections, dendritic cells (DC) are one of the first cells infected by HIV-1 and can transfer virus to more permissive CD4(+) T cells, making these cells an important target for novel antiviral therapies. To extend previous findings with BIT225, we aimed to further characterise the antiviral activity of BIT225 on HIV-1 replication in monocyte-derived DC (MDDC).\", 'The anti-HIV-1 activity of BIT225 was evaluated in vitro within MDDC alone and in co-cultures with activated CD4(+) T cells to examine the effect of the drug on HIV-1 transfer. Antiviral activity was determined by measuring HIV-1 reverse transcriptase activity in the culture supernatant of BIT225 treated and DMSO control cultures. A single dose of BIT225 resulted in a mean (SE) peak inhibition of HIV-1 release from MDDC by 74.5\\xa0% (\u00b10.6) following 14\\xa0days of culture and a 6-fold reduction of HIV-1 transfer to activated uninfected CD4(+) T cells in co-culture.",
            "output": [
                "Does the antiviral compound BIT225 inhibit HIV-1 replication in myeloid dendritic cells?"
            ]
        },
        {
            "id": "task847-bb210d2a4fbb4108bcec68bae511a81d",
            "input": "Critically ill preterm and term neonates are at high risk for negative iron balance due to phlebotomy that occurs with frequent laboratory monitoring, and the high iron demand of rapid growth. Understanding the prioritization of iron between red blood cells (RBCs) and brain is important given iron's role in neurodevelopment.\", 'Ten neonatal twin lamb pairs (n = 20) underwent regular phlebotomy for 11 d. Lambs were randomized to receive no iron or i.v. daily iron supplementation from 1 to 5\\u2009mg/kg. Serum hemoglobin concentration and reticulocyte count were assayed, iron balance calculated, and iron content of RBCs, liver, brain, muscle, and heart measured at autopsy.', 'Among phlebotomized lambs: (i) liver iron concentration was directly related to net iron balance (r = 0.87; P < 0.001) and (ii) brain iron concentration was reduced as a function of net iron balance (r = 0.63) only after liver iron was depleted. In animals with negative iron balance, total RBC iron was maintained while brain iron concentration decreased as a percentage of the iron present in RBCs (r = -0.70; P < 0.01) and as a function of reticulocyte count (r = -0.63; P < 0.05).",
            "output": [
                "Is iron prioritized to red blood cells over the brain in phlebotomized anemic newborn lambs?"
            ]
        },
        {
            "id": "task847-8539713610624f3db07c1b4ec7359710",
            "input": "The previous use of antibiotics is known to correlate positively with antibiotic resistance; whether this is also the case in the eradication of Helicobacter pylori infection is unclear.', 'To investigate the relationship between the previous use of antibiotics and the failure of eradication therapy in H. pylori infection.', 'The relationship between the clinical parameters and the failure of H. pylori eradication was analyzed in patients administered standard triple therapy and then assessed for the eradication of H. pylori based on a C13-urea breath test.', 'In a multivariate analysis, failure rates increased significantly in patients with a history of clarithromycin (odds ratio [OR], 4.445) or other macrolides (OR, 2.407) use, who were female (OR, 1.339), or who were older than 60 years of age (OR, 1.326). The eradication failure rate in patients with a history of macrolides use for >2 weeks was significantly higher than if the duration of use was <2 weeks (44.8% vs. 29.3%, p=0.047).",
            "output": [
                "Do the relationship between the failure to eradicate Helicobacter pylori and previous antibiotics use?"
            ]
        },
        {
            "id": "task847-356a92d7259f432882eeb74c29935b1f",
            "input": "Altered cerebrospinal fluid (CSF) levels of lactate have been described in neurodegenerative diseases and related to mitochondrial dysfunction and neuronal degeneration. We investigated the relationship between CSF lactate levels, disease severity, and biomarkers associated with neuroaxonal damage in patients with multiple sclerosis (MS).', 'One-hundred eighteen subjects with relapsing-remitting multiple sclerosis (RRMS) were included, along with one-hundred fifty seven matched controls. CSF levels of lactate, tau protein, and neurofilament light were detected at the time of diagnosis. Patients were followed-up for a mean of 5 years. Progression index (PI), multiple sclerosis severity scale (MSSS), and Bayesian risk estimate for multiple sclerosis (BREMS) were assessed as clinical measures of disease severity and progression. Differences between groups and correlation between CSF lactate, disease severity and CSF biomarkers of neuronal damage were explored.', 'CSF lactate was higher in RRMS patients compared to controls. A negative correlation was found between lactate levels and disease duration. Patients with higher CSF lactate concentration had significantly higher PI, MSSS, and BREMS scores at long-term follow-up. Furthermore, CSF lactate correlated positively and significantly with CSF levels of both tau protein and neurofilament light protein.",
            "output": [
                "Is cerebrospinal fluid lactate associated with multiple sclerosis disease progression?"
            ]
        },
        {
            "id": "task847-4f2e36659990442f99f7b8f181924306",
            "input": "To determine the effects of a moderate-intensity active workstation on time and error during simulated office work.', 'The aim of the study was to analyse simultaneous work and exercise for non-sedentary office workers. We monitored oxygen uptake, heart rate, sweating stains area, self-perceived effort, typing test time with typing error count and cognitive performance during 30 min of exercise with no cycling or cycling at 40 and 80 W.', 'Compared baseline, we found increased physiological responses at 40 and 80 W, which corresponds to moderate physical activity (PA). Typing time significantly increased by 7.3% (p = 0.002) in C40W and also by 8.9% (p = 0.011) in C80W. Typing error count and cognitive performance were unchanged.",
            "output": [
                "Does active workstation allow office workers to work efficiently while sitting and exercising moderately?"
            ]
        },
        {
            "id": "task847-c3a63aaf25db400b94b6c2b62dad397a",
            "input": "Gastric carcinoids are slow growing neuroendocrine tumours arising from enterochromaffin-like (ECL) cells in the corpus of stomach. Although most of these tumours arise in the setting of gastric atrophy and hypergastrinemia, it is not understood what genetic background predisposes development of these ECL derived tumours. Moreover, diffuse microcarcinoids in the mucosa can lead to a field effect and limit successful endoscopic removal.', 'To define the genetic background that creates a permissive environment for gastric carcinoids using transgenic mouse lines.', 'The multiple endocrine neoplasia 1 gene locus (Men1) was deleted using Cre recombinase expressed from the Villin promoter (Villin-Cre) and was placed on a somatostatin null genetic background. These transgenic mice received omeprazole-laced chow for 6\\u2005months. The direct effect of gastrin and the gastrin receptor antagonist YM022 on expression and phosphorylation of the cyclin inhibitor p27', 'The combination of conditional Men1 deletion in the absence of somatostatin led to the development of gastric carcinoids within 2\\u2005years. Suppression of acid secretion by omeprazole accelerated the timeline of carcinoid development to 6\\u2005months in the absence of significant parietal cell atrophy. Carcinoids were associated with hypergastrinemia, and correlated with increased Cckbr expression and nuclear export of p27",
            "output": [
                "Does deletion of Men1 and somatostatin induce hypergastrinemia and gastric carcinoids?"
            ]
        },
        {
            "id": "task847-3b0c02db4b6a4cc4b321f53af7f1034f",
            "input": "In the Microbicide Trial Network MTN-003 (VOICE) study, a Phase IIB pre-exposure prophylaxis trial of daily oral or vaginal tenofovir (TFV), product adherence was poor based on pharmacokinetic (PK) drug detection in a random subsample. Here, we sought to compare behavioural and PK measures of adherence and examined correlates of adherence misreporting.', 'We included participants with PK and behavioural data from VOICE random subsample. Behavioural assessments included face-to-face interviews (FTFI), audio computer-assisted self-interviewing (ACASI) and pharmacy-returned product counts (PC). TFV concentrations < 0.31 ng/mL in plasma (oral group) and < 8.5 ng/swab in vaginal group were defined as \"PK non-adherent.\" Logistic regression models were fit to calculate the combined predictive ability of the behavioural measures as summarized by area under the curve (AUC). Baseline characteristics associated with over-reporting daily product use relative to PK measures was assessed using a Generalized Linear Mixed Model.', 'In this random adherence cohort of VOICE participants assigned to active products, (N = 472), PK non-adherence was 69% in the oral group (N = 314) and 65% in the vaginal group (N = 158). Behaviourally, \u2264 10% of the cohort reported low/none use with any behavioural measure and accuracy was low (\u2264 43%). None of the regression models had an AUC > 0.65 for any single or combined behavioural measures. Significant (p < 0.05) correlates of over-reporting included being very worried about getting HIV and being unmarried for the oral group; whereas for the vaginal group, being somewhat worried about HIV was associated with lower risk of over-reporting.",
            "output": [
                "Does divergent adherence estimate with pharmacokinetic and behavioural measures in the MTN-003 ( VOICE ) study?"
            ]
        },
        {
            "id": "task847-035a1bb1bdd14efd92021830bdfe00a5",
            "input": "The aim of this study was to investigate the effect of season of diagnosis on the outcome of patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). In this study, we included curatively treated DLBCL (n = 5875) and HL (n = 1693) patients, diagnosed between 2000 and 2011, based on data from the Swedish Lymphoma Register.', 'Overall survival was significantly better for patients diagnosed with DLBCL during the summer months, but not for patients diagnosed with HL. The difference remained in a multivariable analysis adjusted for age, stage, performance status, number of extra nodal sites and year of diagnosis (HR 1.08; 95% CI 1.02-1.14, P = 0.0069). When analyzing the DLBCL patients according to gender in the multivariable model, the effect of season was shown to be restricted to male patients (HR = 1.09, 95% CI 1.01-1.17, P = 0.0269.",
            "output": [
                "Is season of diagnosis associated with overall survival in patients with diffuse large B-cell lymphoma but not with Hodgkin 's lymphoma - A population-based Swedish Lymphoma Register study?"
            ]
        },
        {
            "id": "task847-a6ec2395ba024d1695151a9689598b28",
            "input": "Better prognosis of cancer including hepatocellular carcinoma (HCC) remains unsatisfactory due to recurrence and chemoresistance. In this respect it is important to identify molecular targets specific to the disease in order to design effective therapeutic strategies. In the present study, we investigated the prognostic role of Never-in-mitosis-A-related kinase 2 (NEK2) in HCC.', 'Fifty HCC patients who underwent hepatectomy were enrolled in the study. NEK2 gene and protein expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively.', 'Higher expression of NEK2 was detected in HCC tumoral compared to adjacent non-tumor tissues (p<0.001), and protein expression was also relatively high in tumor than corresponding non-tumor tissues. Furthermore, high NEK2 expression was positively correlated with hepatic venous invasion (p=0.047), des-gammacarboxy prothrombin (p=0.003), and alpha-fetoprotein (AFP) (p=0.024). Patients with high NEK2 expression had significantly poor recurrence-free survival (p=0.042) and early recurrence.",
            "output": [
                "Does high NEK2 Expression be a Predictor of Tumor Recurrence in Hepatocellular Carcinoma Patients After Hepatectomy?"
            ]
        },
        {
            "id": "task847-bd0bd0139ad646e0a7b07e5a011a21ef",
            "input": "To investigate the effect of microtubule stabilization with low-dose paclitaxel on renal fibrosis, focusing on the transforming growth factor-\u03b21 (TGF-\u03b21)-induced plasminogen activator inhibitor-1 (PAI-1) signaling cascade.', \"Forty-eight rats were randomly assigned to four groups: sham/vehicle, sham/paclitaxel, unilateral ureteral obstruction (UUO)/vehicle and UUO/paclitaxel. Rats were treated with a 0.3\\u2009mg/kg intraperitoneal dose of paclitaxel or vehicle twice per week for 14\\u2009days. Half of the rats in each group were sacrificed respectively on day 7 and 14 after operation. Inner medullar collecting duct (IMCD) cells stimulated with TGF-\u03b21 were incubated with 0, 1 and 2 nM paclitaxel for 24 and 72\\u2009hours. Histological changes were assessed using periodic acid-Schiff and Masson's trichrome. The TGF-\u03b21-induced PAI-1 signaling and status of extracellular matrix proteins were evaluated by western blot analysis.\", 'In the UUO kidneys, paclitaxel significantly attenuated tubular damage and interstitial collagen deposition, as well as \u03b1-smooth muscle actin (\u03b1-SMA), TGF-\u03b21 and PAI-1 protein expression. Paclitaxel also inhibited the UUO-induced activation of Smad2/3 and c-Jun N-terminal kinase (JNK). However, paclitaxel treatment did not inhibit extracellular signal-regulated kinase 1/2 (ERK1/2) or p38 expression. In TGF-\u03b21-treated IMCD cells, treatment with 1 and 2 nM paclitaxel for 72\\u2009h reduced fibronectin, \u03b1-SMA and PAI-1 protein expression. Moreover, a 2 nM dose of paclitaxel for 24\\u2009h significantly inhibited the TGF-\u03b21-stimulated activation of Smad2/3, JNK and ERK1/2 in IMCD cells.",
            "output": [
                "Does low-dose paclitaxel ameliorate renal fibrosis by suppressing transforming growth factor-\u03b21-induced plasminogen activator inhibitor-1 signaling?"
            ]
        },
        {
            "id": "task847-a643c15561fe4cbea327e977b0ec586d",
            "input": "RECQ helicase family members act as guardians of the genome to assure proper DNA metabolism in response to genotoxic stress. Hematological malignancies are characterized by genomic instability that is possibly related to underlying defects in DNA repair of genomic stability maintenance.', 'We have investigated the expression of RECQ helicases in different hematological malignancies and in their normal counterparts using publicly available gene expression data. Furthermore, we explored whether RECQ helicases expression could be associated with tumor progression and prognosis.', 'Expression of at least one RECQ helicase family member was found significantly deregulated in all hematological malignancies investigated when compared to their normal counterparts. In addition, RECQ helicase expression was associated with a prognostic value in acute myeloid leukemia, chronic lymphocytic leukemia, lymphoma and multiple myeloma.",
            "output": [
                "Are rECQ helicases deregulated in hematological malignancies in association with a prognostic value?"
            ]
        },
        {
            "id": "task847-4f840fbae9bf48289437349e09501587",
            "input": "Health information has a major role in the planning of future healthcare provision. With current reconfiguration and cost saving measures, further demands are being placed on acute hospitals.', 'To examine the elderly admissions and the referral documentation of older patients admitted to a tertiary level hospital.', 'A retrospective analysis of primary care referral documentation for all acute admissions of patients over 75\\xa0years to University Hospital Limerick (UHL) over a 2-month period. Documentation was analysed on the basis of patient demographics, presenting complaint and referral source. Primary care referral documentation was then analysed on the basis of presenting complaint, patient demographics, referrer details, and the clinical information provided.', \"Over the 2-month period there were a total of 381 elderly admissions through the Emergency department. The most common presenting complaint was with shortness of breath (21.5\\xa0%). 42.5\\xa0% of admissions were from a primary care setting. 31.1\\xa0% of referrals were typed and 47.0\\xa0% handwritten. Over 90\\xa0% of referrals contained the patient's name, date of birth and address. 98.7\\xa0% of referrals included a presenting complaint and 54\\xa0% included a past medical history. 20\\xa0% of referrals listed known drug allergies, while 9.3\\xa0% documented social history or baseline functional status. Referral letters from general practice and after-hour services were largely similar.",
            "output": [
                "Is older patient hospital admissions following primary care referral : the truth in the referring?"
            ]
        },
        {
            "id": "task847-68319c405fb04152812ae5619353fae1",
            "input": "Protein and energy malnutrition is a severe problem for patients with liver cirrhosis (LC) and fasting often induces starvation which is a vitally important outcome. Dietary restriction is essential for endoscopic injection sclerotherapy (EIS) in patients with risky esophageal varices, thereby creating the possible exacerbation of nutritional state and inducing liver dysfunction. Whether EIS induces nutritional deficiency in LC patients and the effects of branched-chain amino acid (BCAA)-enriched nutrient are prospectively investigated.', 'A total of 61 LC patients were randomly divided into an EIS monotherapy group (non-BCAA group, n\\u2009=\\u200931) and an EIS combined with BCAA therapy group (n\\u2009=\\u200930). Platelet count, blood chemistry and somatometry values were prospectively measured at five time points.', 'The platelet counts before treatment were at the same level in both groups (P\\u2009=\\u20090.72). Three months after treatment, the counts decreased in the non-BCAA group; however, they increased in the BCAA group (P\\u2009=\\u20090.019). Body mass index, triceps skin fold thickness and arm muscle circumference significantly decreased in both groups. The BCAA and tyrosine ratio value increased only in the BCAA group (P\\u2009<\\xa00.01). The skeletal muscle volume measured by InBody720 significantly decreased in the non-BCAA group (P\\u2009<\\xa00.001).",
            "output": [
                "Does branched-chain amino acid-enriched nutrient increase blood platelet count in patients after endoscopic injection sclerotherapy?"
            ]
        },
        {
            "id": "task847-2a43374580114f72806f1d75bd45b7af",
            "input": "Recent studies have indicated a protective role of physiological autophagy in ischemic heart disease. However, the underlying mechanisms of autophagy regulation after ischemia are poorly understood. Exosomes are nano-sized vesicles released from cells that play critical roles in mediating cell-to-cell communication through the transfer of microRNAs. In this study, we observed that miR-30a was highly enriched in exosomes from the serum of acute myocardial infarction (AMI) patients in vivo and culture medium of cardiomyocytes after hypoxic stimulation in vitro. We also found that hypoxia inducible factor (HIF)-1\u03b1 regulates miR-30a, which efficiently transferred via exosomes between cardiomyocytes after hypoxia. Inhibition of miR-30a or release of exosomes increased the expression of the core autophagy regulators beclin-1, Atg12, and LC3II/LC3I, which contributed to maintaining the autophagic response in cardiomyocytes after hypoxia. Taken together, the present study showed that exosomes from hypoxic cardiomyocytes regulate autophagy by transferring miR-30a in a paracrine manner, which revealed a new pathway of autophagy regulation that might comprise a promising strategy to treat ischemic heart disease.",
            "output": [
                "Does exosomal transfer of miR-30a between cardiomyocytes regulate autophagy after hypoxia?"
            ]
        },
        {
            "id": "task847-580105ad12ae4825882fd5cd80cc7b07",
            "input": "Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12-week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM.', 'Fifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12-week follow-up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry-based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise.', 'Compared to the control group, the exercise group improved in minutes of cycling time (P\\u2009<\\u20090.01) and Vo2 max (P\\u2009<\\u20090.05). The exercise group also had reduced disease activity (P\\u2009<\\u20090.05) and reduced lactate levels at exhaustion (P\\u2009<\\u20090.05). Genes related to capillary growth, mitochondrial biogenesis, protein synthesis, cytoskeletal remodeling, and muscle hypertrophy were up-regulated in the exercise group, while genes related to inflammation/immune response and endoplasmic reticulum stress were down-regulated. Mitochondrial pathways including the oxidative phosphorylation metabolic pathway were most affected by the endurance exercise, as demonstrated by proteomics analysis. The exercise group also showed a higher number of capillaries per mm(2) in follow-up biopsy samples (P\\u2009<\\u20090.05).",
            "output": [
                "Does endurance Exercise improve Molecular Pathways of Aerobic Metabolism in Patients With Myositis?"
            ]
        },
        {
            "id": "task847-a4bf122b42514d8b8727b07247e9c6d5",
            "input": "\"Virtual fracture clinics\" have been reported as a safe and effective alternative to the traditional fracture clinic. Robust protocols are used to identify cases that do not require further review, with the remainder triaged to the most appropriate subspecialist at the optimum time for review. The objective of this study was to perform a \"top-down\" analysis of the cost effectiveness of this virtual fracture clinic pathway.', 'National Health Service financial returns relating to our institution were examined for the time period 2009 to 2014 which spanned the service redesign.', 'The total staffing costs rose by 4% over the time period (from \u00a31 744 933 to \u00a31 811 301) compared with a national increase of 16%. The total outpatient department rate of attendance fell by 15% compared with a national fall of 5%. Had our local costs increased in line with the national average, an excess expenditure of \u00a3212 705 would have been required for staffing costs.",
            "output": [
                "Does fracture clinic redesign reduce the cost of outpatient orthopaedic trauma care?"
            ]
        },
        {
            "id": "task847-97580be24e554d20b03629811087d73a",
            "input": "Helicobater (H.) pylori eradication rates with standard first-line triple therapy have declined to unacceptable levels. To date, amoxicillin-resistant H. pylori strains have rarely been detected. Whether increasing the dosage of amoxicillin in a standard 7 days eradicating regimen may enhance its efficacy is not known. The aim of this paper is to compare the efficacy of a 7 days high-dose amoxicillin based first-line regimen with sequential therapy.', 'We have retrospectively analyzed data from 300 sex and age matched patients, who underwent 3 different therapeutic schemes: (1) standard LCA, lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid for 7 days; (2) high dose LCA (HD-LCA), lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg tid for 7 days; (3) sequential LACT, lansoprazole 30 mg bid plus amoxicillin 1000 mg bid for 5 days, followed by lansoprazole 30 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for 5 days. Eradication was confirmed by 13C-urea breath test. Compliance and occurrence of adverse effects were also assessed.', 'Eradication rates were: 55% for LCA, 75% for HD-LCA and 73% for LACT. Eradication rates were higher in HD-LCA group compared to LCA (p<0.01), while no significant differences were observed in HD-LCA group compared to LACT (p=ns). Compliance and occurrence of adverse effects were similar among groups.",
            "output": [
                "Is high dose amoxicillin-based first line regimen equivalent to sequential therapy in the eradication of H. pylori infection?"
            ]
        },
        {
            "id": "task847-cc17468900344d678c26f3f103ca295c",
            "input": "Non-shockable rhythms represent an increasing proportion of reported cases of out-of-hospital cardiac arrest but with an associated poor prognosis. In the present study, we investigated the effects of hydrogen inhalation on cardiac and neurological function after cardiopulmonary resuscitation and compared the therapeutic benefit with hypothermia in an asphyxial rat model of cardiac arrest.', 'Cardiopulmonary resuscitation was initiated after 5 min of untreated asphyxial cardiac arrest. Animals were randomly assigned to three experimental groups immediately after successful resuscitation: ventilation with 2% hydrogen/98% oxygen under normothermia (H2 inhalation), ventilation with 2% nitrogen/98% oxygen under normothermia (Control), and ventilation with 2% nitrogen/98% oxygen under hypothermia (TH). Mixed gas inhalation continued for 1 h while hypothermia continued for 2\\u200ah. Animals were observed up to 96\\u200ah for assessment of survival and neurologic recovery.', 'No statistical differences in baseline measurements were observed among groups and all the animals were successfully resuscitated. Serum cardiac troponin T and S100B measured during earlier post-resuscitation period were markedly reduced in both H2 inhalation and hypothermic groups. However, significantly better left ventricular ejection fraction, cardiac work, and neurological deficit score were observed in the H2 inhalation group. Ninety-six hours survival rate was significantly higher in the H2 inhalation group (75.0%), either compared with TH (45.8%) or compared with Control (33.3%). But there was no statistical difference between TH and Control.",
            "output": [
                "Is hydrogen Inhalation Superior to Mild Hypothermia in Improving Cardiac Function and Neurological Outcome in an Asphyxial Cardiac Arrest Model of Rats?"
            ]
        },
        {
            "id": "task847-45c15504fb7041de951edb30fd9ba5fa",
            "input": "Gastric cancer (GC) is widely associated with chronic inflammation. The pro inflammatory microenvironment provides conditions that disrupt stem/progenitor cell proliferation and differentiation. The signal transducer and activator of transcrip- tion-3 (STAT3) signaling pathway is involved in inflammation and also contributes to the maintenance of embryonic stem cell (ESCs) pluripotency. Here, we have investi- gated the activation status of STAT3 in GC stem-like cells (GCSLCs).', 'In this experimental research, CSLCs derived from the human GC cell line MKN-45 and patient specimens, through spheroid body formation, character- ized and then assayed for the STAT3 transcription factor expression in mRNA and protein level further to its activation.', 'Spheroid cells showed higher potential for spheroid formation than the pa- rental cells. Furthemore, stemness genes NANOG, c-MYC and SOX-2 were over expressed in spheroids of MKN-45 and in patient samples. In MKN-45 spheroid cells, epithelial mesenchymal transition (EMT) related markers CDH2, SNAIL2, TWIST and VIMENTIN were upregulated (P<0.05), but we observed no change in expression of the E-cadherin epithelial marker. These cells exhibited more resistance to docetaxel (DTX) when compared with parental cells (P<0.05) according to the MTS assay. Al- though immunostaining and Western blotting showed expression of the STAT3 pro- tein in both spheroids and parents, the mRNA level of STAT3 in spheroids was higher than the parents. Nuclear translocation of STAT3 was accompanied by more intensive phospho-STAT3 (p-STAT3) in spheroid structures relative to the parent cells accord- ing to flow cytometry analysis (P<0.05).",
            "output": [
                "Is sTAT3 Overactivated in Gastric Cancer Stem-Like Cells?"
            ]
        },
        {
            "id": "task847-071e7306e8e44dc3b2288da9d7ef7198",
            "input": "Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a \u03b2-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model.', 'Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal.', 'Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment.",
            "output": [
                "Does valsartan attenuate cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling?"
            ]
        },
        {
            "id": "task847-d7f59351b1334f09ab106dab0f24fb6d",
            "input": "This study is to evaluate the effect of high-volume hemofiltration (HVHF) and early goal-directed therapy (EGDT) on alveolar-arterial oxygen exchange in patients with refractory septic shock.', 'Patients were classified into two groups by a prospective cohort study: 86 received both HVHF and EGDT (the HVHF group), and 81 treated with EGDT only (the control group). Alveolar-arterial oxygen pressure was taken at baseline and at days 1, 3, and 7, and respiratory index (RI, ratio of P(a)O2 alveolar-arterial oxygen pressure difference (P(A-a)DO2) to arterial oxygen pressure (P(a)O2) was calculated.', 'At day 7, the levels of central venous and arterial blood oxygen content were significantly higher in the HVHF vs. the control group (both with p < 0.05). The level of oxygen extraction ratio (O2ER) was significantly higher in the HVHF than the control group (p < 0.01). The levels of P(A-a)DO2 and RI were significantly lower in the HVHF than the control group (p < 0.05 and p < 0.01, respectively). RI and the ratio of P(a)O2 to the fraction of inspired oxygen were significantly higher in the HVHF than the control group (p < 0.05 and p < 0.01, respectively). The acute physiology and chronic health evaluation score and the sequential organ failure assessment score in the HVHF group were significantly lower compared to the control group (p < 0.01 and p < 0.05, respectively). At day 28, the mortality rate was lower in the HVHF vs. the control group (p < 0.01).",
            "output": [
                "Does high-volume hemofiltration combined with early goal-directed therapy improve alveolar-arterial oxygen exchange in patients with refractory septic shock?"
            ]
        },
        {
            "id": "task847-4bd2a09ea9734161870374ddf63f61a0",
            "input": "Immune activation contributes to the persistent state of inflammation associated with metabolic dysfunction in obesity. The specific immune receptors that sense metabolic stress signals and trigger inflammation are nevertheless largely unknown, and little is known on inflammatory and immune gene regulation in obesity.', 'The study includes a cross-sectional and a longitudinal arm. Forty children and adolescents were enrolled: 22 obese subjects and 18 age-matched normal weight controls. Obese subjects participated in an 18-month therapeutic protocol, based on intensive lifestyle modification (dietary regimen, physical activity and behavioral interventions). Expression of genes involved in the inflammasome pathway, plasma concentration of the inflammasome-associated pro-inflammatory cytokines (interleukin (IL)-1\u03b2 and IL-18) and indexes of microbial translocation (lipopolysaccharide (LPS), soluble CD14 (sCD14) and intestinal fatty acid-binding protein) were analyzed at baseline in obese subjects compared with controls, and after 18 months in obese subjects.', 'Cross-sectional analyses showed that the LPS-induced expression of genes involved in inflammasome (NLRP3, caspase 5 and NAIP), Nod-like receptors (NLRX1 and NOD1), downstream signaling (P2RX7, RAGE, RIPk2, TIRAP and BIRC2) and effector molecules (IFN-\u03b3, IL-12\u03b2, IL-1\u03b2, CCL2, CCL5, IL-6 and TNF\u03b1) was significantly increased in obese subjects at baseline as compared with normal weight controls. The baseline plasma concentration of inflammasome-related cytokines (IL-1\u03b2 and IL-18) and of microbial translocation markers (LPS and sCD14) was augmented in obese subjects as compared with controls as well. Longitudinal analyses indicated that intensive lifestyle modification resulted in a normalization of parameters in subjects with a significant reduction of BMI after 18 months.",
            "output": [
                "Are upregulation of inflammasome activity and increased gut permeability associated with obesity in children and adolescents?"
            ]
        },
        {
            "id": "task847-5adaba88993b4987a7a72ee9d452e907",
            "input": "Does asking for the percentage of time spent sitting during work (P-method) instead of asking for the absolute length of time spent sitting (T-method) improve properties of the workers' sitting- and walking-time questionnaire (WSWQ)? The purpose of this study was to investigate whether questioning technique influences test-retest reliability and criterion validity of the WSWQ.\", \"Sixty-five Japanese workers completed each version of the WSWQ in random order. Both questionnaires assessed quantities of time spent sitting or walking (including standing) during work time, non-working time on a workday, and anytime on a non-workday. Participants wore the thigh-worn inclinometer (activPAL) as criterion measure. Intraclass correlation coefficients (ICC) and Spearman's \u03c1 were used for the analyses.\", \"For all three domains, values of reliability and validity with the P-method tended to be higher than with the T-method: ICC values ranged from 0.48-0.85 for the T-method and from 0.71-0.85 for the P-method; Spearman's \u03c1 values ranged from 0.25-0.58 for the T-method and from 0.42-0.65 for the P-method. The validities with both methods on a workday (0.51-0.58 for the T-method and 0.56-0.65 for the P-method) were higher than validities on a non-workday (0.25-0.45 for the T-method and 0.42-0.60 for the P-method). In post-survey interviews, 48 participants (77%) chose the P-method as their preferred questioning style.",
            "output": [
                "Does percentage-Method improve Properties of Workers ' Sitting- and Walking-Time Questionnaire?"
            ]
        },
        {
            "id": "task847-60dcae3a71844676a98d1e4564e84d32",
            "input": "To evaluate the cytotoxic and apoptotic effects of bishydroxycoumarin (BHC) against human glioma cells and to study their mode of action.', 'Three cells were used in the experiments. MTT and LDH assays were used to assess the cytotoxic effects of BHC while an in vitro wound healing assay was used to study the effect of BHC on cell migration. Fluorescence microscopy and annexin V-FITC assay were used to study the cellular morphology and apoptotic effects while flow cytometry in combination with propidium iodide (PI) were used to study cell cycle arrest induced by BHC.', 'BHC induced substantial and dose-dependent cytotoxic effects against all three cell lines with U87MG cell line being most susceptible. BHC also inhibited cell migration and induced characteristic morphological changes including chromatin condensation, nuclear shrinkage which increased with increasing dose of BHC. The apoptotic cell population (both early and late apoptotic cells) increased with increasing dose of BHC which also induced substantial G0/G1 cell cycle growth arrest in U87MG cells.",
            "output": [
                "Are anticancer effects of bishydroxycoumarin mediated through apoptosis induction , cell migration inhibition and cell cycle arrest in human glioma cells?"
            ]
        },
        {
            "id": "task847-0d4761271bdc4ca299c3b422f2d81a8c",
            "input": "To investigate the prognostic value of weight loss before diagnosis in patients with advanced stage non-small cell lung cancer (NSCLC) treated with first-line chemotherapy.', 'A total of 81 NSCLC patients with stages IIIB/IV were included in this retrospective cross-sectional study. Study variables were weight loss in the last 3 months before diagnosis, patient demographic, clinical and laboratory characteristics and histological features of the tumor before administering first-line chemotherapy. Then, the patients were stratified into 4 groups based on their weight loss before being diagnosed with NSCLC.', 'The patients were predominantly male (68%), with a smoking history (62%), 5 to 10 kg weight loss in the last 3 months (31%), and had metastatic disease (64%) and adenocarcinoma (40%) at the time of diagnosis. On the other hand, most of the patients with 5 to 10 kg weight loss in the last 3 months before diagnosis had squamous cell carcinoma (44%), stage IV disease (56%), and the first disease progression was in the brain (64%). Pre-diagnosis weight loss had a negative impact on progression-free survival (PFS), independent from weight loss during first-line chemotherapy, but no such effect was noticed on overall survival (OS).",
            "output": [
                "Is weight loss at the time of diagnosis associated with prognosis in patients with advanced-stage non-small cell lung cancer?"
            ]
        },
        {
            "id": "task847-244b8cef06294ac8b2fee88e0fdc8254",
            "input": "Sigma-1 receptors are involved in the pathophysiological process of several neuropsychiatric diseases such as epilepsy, depression. Allosteric modulation represents an important mechanism for receptor functional regulation. In this study, we examined antidepressant activity of the latest identified novel and selective allosteric modulator of sigma-1 receptor 3-methyl-phenyl-2, 3, 4, 5-tetrahydro-1H-benzo[d]azepin-7-ol (SOMCL-668).', 'A single administration of SOMCL-668 decreased the immobility time in the forced swimming test (FST) and tailing suspended test in mice, which were abolished by pretreatment of sigma-1 receptor antagonist BD1047. In the chronic unpredicted mild stress (CUMS) model, chronic application of SOMCL-668 rapidly ameliorated anhedonia-like behavior (within a week), accompanying with the enhanced expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of glycogen synthase kinase 3\u03b2 (GSK3\u03b2) (Ser-9) in the hippocampus. SOMCL-668 also rapidly promoted the phosphorylation of GSK3\u03b2 (Ser-9) in an allosteric manner in vitro. In the cultured primary neurons, SOMCL-668 enhanced the sigma-1 receptor agonist-induced neurite outgrowth and the secretion of BDNF.",
            "output": [
                "Does allosteric Modulation of Sigma-1 Receptors elicit Rapid Antidepressant Activity?"
            ]
        },
        {
            "id": "task847-a7ad0b192b354eadac4584bde4bc6628",
            "input": "The CARD14 gene encodes a protein that enhances nuclear factor (NF)-\u03baB activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti-TNF) therapies among patients with psoriasis.', 'To determine whether CARD14 gene variants were linked to a significant positive anti-TNF response in patients with psoriasis.', 'DNA from 116 patients with psoriasis was subjected to next-generation sequencing of the CARD14 gene. All of the patients were nonresponders or had contraindications to conventional systemic treatments.', 'A reduction of at least 75% in Psoriasis Area and Severity Index (PASI 75) at week 24 was considered a positive response to treatment. In total 116 patients (79 responders and 37 nonresponders) were next-generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all of the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (P = 0.01, odds ratio 3.71, 95% confidence interval 1.30-10.51). Furthermore, among responders, six patients were heterozygous carriers of the rare p.Glu422Lys variant, and two patients were heterozygous for p.Arg682Trp (P = 0.04).",
            "output": [
                "Do common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis?"
            ]
        },
        {
            "id": "task847-f4d872cdddc444a8b1946c94e47f1205",
            "input": "Screening and referral for geriatric depression by service agencies is associated with poor treatment engagement indicating the need to transform services to directly provide depression care.', 'To describe a multi-organization workgroup implementation planning process used to transform a community-based screening and referral program to provide a brief evidence-based intervention for older adults with depressive symptoms.', 'An iterative implementation procedure used by a multi-stakeholder group that selected an evidence-based practice, planned implementation rollout, planned counselor training, and designed an implementation evaluation.', 'The workgroup successfully followed the implementation procedure and developed a plan for the implementation of an evidence-based intervention. Overall, the workgroup prioritized decisions that favored feasibility and low implementation burden.",
            "output": [
                "Do a Multi-Stakeholder Process to Transform a Community-based Screening and Referral Program to Implement Evidence-Based Depression Care?"
            ]
        },
        {
            "id": "task847-25346b5dbdcb4e2f9d0e5866f07e3770",
            "input": "L-Carnosine inhibits senescence of somatic cells and displays anticancer activity. Here we analyzed if L-carnosine (20 mM) retards senescence of human peritoneal mesothelial cells (HPMCs) and inhibits progression of ovarian cancer cells.', 'Experiments were performed with primary HPMCs established from patients undergoing abdominal surgery and with three ovarian cancer cell lines: A2780, OVCAR-3 and SKOV-3.', 'L-Carnosine retards senescence of HPMCs plausibly via inhibition of mitochondria-related oxidative stress. Prolonged exposure of HPMCs to L-carnosine prevented senescent HPMC-dependent exacerbation of cancer cell adhesion, migration, invasion and proliferation, which may be linked with decreased secretion of various pro-cancerogenic agents by HPMCs. Cancer cells exposed directly to L-carnosine displayed reduced viability, increased frequency of apoptosis and unaltered proliferation.",
            "output": [
                "Does l-Carnosine prevent the Pro-cancerogenic Activity of Senescent Peritoneal Mesothelium Towards Ovarian Cancer Cells?"
            ]
        },
        {
            "id": "task847-24052cc8b6c545c5a132cd55bf570157",
            "input": "Interleukin-6 (IL-6) is a vital inflammatory factor in the peritoneal cavity of peritoneal dialysis (PD) patients. Because intraperitoneal inflammation is closely associated with angiogenesis, we sought to explore the effect of IL-6 on vascular endothelial growth factor (VEGF) synthesis and its transduction pathway in mesothelial cells.', 'Human mesothelial cells (Met-5A) were incubated with different concentrations of glucose and mannitol, and the effect of glucose and mannitol on the expression of IL-6 was determined. Then, the cells were stimulated by IL-6 with or without two soluble receptors of IL-6 (sIL-6R or sgp130), and VEGF synthesis was detected. Finally, the cells were incubated with IL-6/sIL-6R combined with or without the inhibitor of Janus kinases (JAK) AG490. The phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and its intracellular translocation were examined.', '1. High glucose and mannitol could up-regulate IL-6 mRNA expression and IL-6 secretion in mesothelial cells significantly, and there was no difference of its effect between high glucose and mannitol. 2. Met-5A was a cell line with a single IL-6 receptor. The IL-6/sIL-6R complex induced VEGF synthesis of mesothelial cells, which was alleviated by sgp130 or AG490. IL-6 trans-signaling could induce the phosphorylation of STAT3, which is recruited to the cellular nucleus of Met-5A cells.",
            "output": [
                "Does interleukin-6 trans-signaling induce VEGF synthesis partly via Janus kinases-STAT3 pathway in human mesothelial cells?"
            ]
        },
        {
            "id": "task847-9b6ff87c35d9476dad3463b5eca7a42d",
            "input": "To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC).', 'Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A \u03c7(2) test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics.', 'Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (\u2265 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed.",
            "output": [
                "Does staging laparoscopy improve treatment decision-making for advanced gastric cancer?"
            ]
        },
        {
            "id": "task847-1d2cda4ec74745f6b3ccc265442bce90",
            "input": "This study aimed to determine if the ratio of cortical thickness to shaft diameter of the humerus, as measured on a simple anterior-posterior shoulder radiograph, is associated with surgical fixation failure.', '64 consecutive fractures in 63 patients (mean age 66.1 years, range 35-90) operated with surgical fixation between March 2011 and July 2014 using PERI-LOC locking plate and screws (Smith and Nephew, UK) were identified. Predictors of bone quality were measured from preoperative radiographs, including ratio of the medial cortex to shaft diameter (medial cortical ratio, MCR). Loss of fixation (displacement, screw cut out, or change in neck-shaft angle >4 degrees) was determined on follow-up radiographs.', 'Loss of fixation occurred in 14 patients (21.9%) during the follow up. Patients were older in the failure group 72.8 vs. 64.2 years (p=0.007). The MCR was significantly lower in patients with failed fixation 0.170 vs 0.202, p=0.019. Loss of fixation is three times more likely in patients with a MCR <0.16 (41% vs. 14%, p=0.015). Increased fracture parts led to increased failure rate (p=0.0005).",
            "output": [
                "Is simple radiographic assessment of bone quality associated with loss of surgical fixation in patients with proximal humeral fractures?"
            ]
        },
        {
            "id": "task847-8a99bcbb4cfd46d49501c9cce8652b89",
            "input": "Recent studies have demonstrated that mouthwash made with the traditional Japanese medicine hangeshashinto exhibits anti-inflammatory action and alleviates oral mucositis scores, including pain complaints, in patients undergoing chemoradiotherapy. However, no study has demonstrated the mechanism underlying how hangeshashinto provides pain relief in oral ulcers.', 'The analgesic effects on pain-related behaviors following the topical application of hangeshashinto were evaluated in an oral ulcer rat model treated with acetic acid using recently developed methods. Indomethacin, the representative anti-inflammatory agent, was intraperitoneally administered. The tissue permeability of the oral mucosa was histologically evaluated after applying the fluorescent substance FluoroGold.', 'The topical application of hangeshashinto in ulcerative oral mucosa suppressed mechanical pain hypersensitivity over 60 min, without any effects on healthy mucosa. The same drug application also inhibited oral ulcer-induced spontaneous pain. Indomethacin administration failed to block the mechanical pain hypersensitivity, though it did largely block spontaneous pain. Topical anesthesia with lidocaine showed hyposensitivity to mechanical stimulation in healthy mucosa. In the ulcer regions in which the oral epithelial barrier was destroyed, deep parenchyma was stained with FluoroGold, in contrast to healthy oral mucosa, in which staining was limiting to the superficial site.",
            "output": [
                "Does the traditional Japanese medicine hangeshashinto alleviate oral ulcer-induced pain in a rat model?"
            ]
        },
        {
            "id": "task847-ed6d2251dd7b4c1985c1894d10568125",
            "input": "Skeletal muscle fibers are multinucleated syncytia that arise from the fusion of mononucleated precursors, the myocytes, during embryonic development, muscle hypertrophy in post-embryonic growth and muscle regeneration after injury. Even though myocyte fusion is central to skeletal muscle differentiation, our current knowledge of the molecular mechanism of myocyte fusion in the vertebrates is rather limited. Previous work, from our group and others, has shown that the zebrafish embryo is a very useful model for investigating the cell biology and genetics of vertebrate myocyte fusion in\\xa0vivo.', 'Here, we report the generation of a stable transgenic zebrafish strain that expresses the Histone 2B-GFP (H2B-GFP) fusion protein in the nuclei of all fast-twitch muscle fibers under the control of the fast-twitch muscle-specific myosin light chain, phosphorylatable, fast skeletal muscle a (mylpfa) gene promoter. By introducing this transgene into a mutant for junctional adhesion molecule 3b (jam3b), which encodes a cell adhesion protein previously implicated in myocyte fusion, we demonstrate the feasibility of using this transgene for the analysis of myocyte fusion during the differentiation of the trunk musculature of the zebrafish embryo.",
            "output": [
                "Is the zebrafish fast myosin light chain mylpfa : H2B-GFP transgene a useful tool for in vivo imaging of myocyte fusion in the vertebrate embryo?"
            ]
        },
        {
            "id": "task847-724b38fddc6649a3953bf7d1bfd1c5f2",
            "input": "Many insect cytochrome P450s (CYPs) play critical roles in detoxification of insecticides. The CYP6 family is unique to the class Insecta, and its biochemical function has essentially been associated with the metabolism of xenobiotics. In this study, we sequenced and characterised the full-length cDNAs of five CYP genes from Locusta migratoria, a highly destructive agricultural pest worldwide.', 'The five genes were predominantly expressed in brain, guts, fat bodies or Malpighian tubules. CYP6FE1, CYP6FF1 and CYP6FG1 were expressed at higher levels in fourth-instar nymphs than in other developmental stages. CYPFD2 is specifically expressed in adults, whereas CYP6FD1, CYP6FD2 and CYP6FE1 showed significantly lower expression in eggs than in other developmental stages. Deltamethrin suppressed CYP6FD1 expression in third-instar nymphs and upregulated the expression level of CYP6FD2, CYP6FF1 and CYP6FG1 at the dose of LD",
            "output": [
                "Does rNA interference of cytochrome P450 CYP6F subfamily genes affect susceptibility to different insecticides in Locusta migratoria?"
            ]
        },
        {
            "id": "task847-c39b804433af4478b3ead2ac8459a7be",
            "input": "Small cell lung cancer (SCLC) is an extremely aggressive disease, commonly displaying therapy-resistant relapse. We have previously identified neuroendocrine and epithelial phenotypes in SCLC tumours and the neuroendocrine marker, pro-opiomelanocortin (POMC), correlated with worse overall survival in patients. However, the effect of treatment on these phenotypes is not understood. The current study aimed to determine the effect of repeated irradiation treatment on SCLC cell phenotype, focussing on the neuroendocrine marker, POMC.', 'Human SCLC cells (DMS 79) were established as subcutaneous xenograft tumours in CBA nude mice and then exposed to repeated 2Gy irradiation. In untreated animals, POMC in the blood closely mirrored tumour growth; an ideal characteristic for a circulating biomarker. Following repeated localised irradiation in vivo, circulating POMC decreased (p< 0.01), in parallel with a decrease in tumour size, but remained low even when the tumours re-established. The excised tumours displayed reduced and distinctly heterogeneous expression of POMC compared to untreated tumours. There was no difference in the epithelial marker, cytokeratin. However, there were significantly more N-cadherin positive cells in the irradiated tumours. To investigate the tumour response to irradiation, DMS79 cells were repeatedly irradiated in vitro and the surviving cells selected. POMC expression was reduced, while mesenchymal markers N-cadherin, \u03b21-integrin, fibroblast-specific protein 1, \u03b2-catenin and Zeb1 expression were amplified in the more irradiation-primed cells. There were no consistent changes in epithelial marker expression. Cell morphology changed dramatically with repeatedly irradiated cells displaying a more elongated shape, suggesting a switch to a more mesenchymal phenotype.",
            "output": [
                "Does irradiation decrease the Neuroendocrine Biomarker Pro-Opiomelanocortin in Small Cell Lung Cancer Cells In Vitro and In Vivo?"
            ]
        },
        {
            "id": "task847-228311c265124716a6474eec66f2c756",
            "input": "To investigate the therapeutic effects and mechanisms of interleukin (IL)-22 in liver regeneration in mice with concanavalin A (ConA)-induced liver injury following 70% hepatectomy.', 'Mice were injected intravenously with ConA at 10 \u03bcg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 \u03bcg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline.', 'IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3 (STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein mRNA expression was significantly elevated after IL-22 treatment.",
            "output": [
                "Does interleukin-22 contribute to liver regeneration in mice with concanavalin A-induced hepatitis after hepatectomy?"
            ]
        },
        {
            "id": "task847-b49412636dbc49a3b586dbe14c3bc6fe",
            "input": "To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT).', 'We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by \u03c7(2) test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression.', 'Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 \u00b1 3.41 ng/mL vs 4.47 \u00b1 2.22 ng/mL, P < 0.05). Furthermore, NODM group recipients had lower 1-, 5-, 10-year overall survival rates (86.7%, 71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P < 0.05) and allograft survival rates (92.8%, 84.6%, and 75.7% vs 96.1%, 91%, and 86.1%, P < 0.05) than the others. The best cutoff of mean cTAC for predicting NODM was 5.89 ng/mL after 6 mo after LT. Multivariate analysis showed that old age at the time of LT (> 50 years), hypertension pre-LT, and high mean cTAC (\u2265 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy.",
            "output": [
                "Does minimizing tacrolimus decrease the risk of new-onset diabetes mellitus after liver transplantation?"
            ]
        },
        {
            "id": "task847-6651d35c74434a329f110a4760fa0315",
            "input": "Helicobacter pylori induces chronic inflammation and intestinal metaplasia (IM) through genetic and epigenetic changes and activation of intracellular signaling pathways that contribute to gastric carcinogenesis. However, the precise mechanism of IM in gastric carcinogenesis has not been fully elucidated. We previously found that intestine-specific homeobox (ISX) mRNA expression increased in organoids cultured from Helicobacter-infected mouse mucosa. In this study, we elucidate the role of ISX in the development of IM and gastric carcinogenesis.', 'ISX expression was assessed in Helicobacter-infected mouse and human gastric mucosa. MKN45 gastric cancer cells were co-cultured with H. pylori to determine whether Helicobacter infection induced ISX expression. We established stable MKN45 transfected cells expressing ISX (Stable-ISX MKN45) and performed a spheroid colony formation assay and a xenograft model. We performed ISX immunohistochemistry in cancer and adjacent gastric tissues.', 'ISX expression was increased in mouse and human gastric mucosa infected with Helicobacter. The presence of IM and H. pylori infection in human stomach was correlated with ISX expression. H. pylori induced ISX mRNA and protein expression. CDX1/2, cyclinD1, and MUC2 were upregulated in Stable-ISX MKN45, whereas MUC5AC was downregulated. Stable-ISX MKN45 cells formed more spheroid colonies, and had high tumorigenic ability. ISX expression in gastric cancer and adjacent mucosa were correlated.",
            "output": [
                "Does intestine-specific homeobox ( ISX ) induce intestinal metaplasia and cell proliferation to contribute to gastric carcinogenesis?"
            ]
        },
        {
            "id": "task847-85c3f0f7d67645f9a49db6e4b3422cc2",
            "input": "Reactive oxygen species have been recognized to impair cell function through suppressing Akt the well-known pro-survival molecule. Pile of concrete evidence imply metformin as an Insulin sensitizer may enhance Akt/mTOR activity however the significance of Akt/mTOR recruitment has not yet been revealed in metformin induced neuroprotection against oxidative stress.', 'In the current study using H2O2 induced injury in PC12 cells; we first examined metformin impact on cell death by MTT assay and visual assessment. Metformin pretreated cells were then subjected to immunoblotting as well as real time PCR to find PI3K, Akt, mTOR and S6K concurrent transcriptional and post-transcriptional changes. The proportions of phosphorylated to non-phosphorylated constituents of PI3K/Akt/mTOR/S6K were determined to address their activation upon metformin treatment.', 'According to cells morphology and MTT data metformin led to significant protection against H2O2 induced injury in 0.1 and 0.5mM concentrations. Metformin induced protection concurred with elevated PI3K/Akt/mTOR/S6K activity as well as enhanced GSH levels. These changes paralleled with a profound decline in the corresponding transcripts as determined by real time PCR.",
            "output": [
                "Is metformin-induced protection against oxidative stress associated with AKT/mTOR restoration in PC12 cells?"
            ]
        },
        {
            "id": "task847-0c53a772ae8941079639cde8f4790008",
            "input": "Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular pattern recognition receptor, which plays an important role in the innate immunity and inflammation. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. In this study, we sought to determine the role of NOD2 on cardiac I/R injury.', 'Mice were induced 30min ischemia followed by 24h of reperfusion. Histological examinations were performed on heart sections with Evans blue and triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence staining. The messenger RNA (mRNA) expression and protein levels were detected by real-time polymerase chain reaction (RT-PCR) and western blot analysis respectively.', 'I/R injury markedly upregulated NOD2 expression in heart tissue. Treatment of WT mice with NOD2 ligand (MDP) significantly increased infarct size, the number of apoptotic cells and inflammatory cells, as compared with wild-type mice after I/R injury. Furthermore, MDP enhanced I/R-induced cardiomyocyte apoptosis and inflammation in vitro, and these effects were attenuated by NOD2-siRNA. The mechanism of NOD2 on cardiac I/R injury is partly associated with JNK, p38MAPK and NF-\u03baB signaling pathways.",
            "output": [
                "Does nOD2 contribute to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and inflammation?"
            ]
        },
        {
            "id": "task847-b7691aceacb34d4a887b740e12d31be0",
            "input": "The nucleolar 58-kDa microspherule protein (MSP58) has important transcriptional regulation functions and plays a crucial role in the tumorigenesis and progression of cancers. 3'-deoxy-3'-[18F]fluorothymidine (FLT) has emerged as a promising positron emission tomography (PET) tracer for evaluating tumor malignancy and cell proliferation.\", 'In the present study, the expression of MSP58 was evaluated by immunohistochemistry and the corresponding PET image was examined using FLT-PET in 55 patients with various grades of gliomas.', 'The immunoreactivity score (IRS) of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P < 0.001). The IRS of MSP58 in the tumor showed a highly significant positive correlation with corresponding FLT uptake value (r = 0.61, P < 0.001). The correlation between MSP58 expression and glioma malignancy was also confirmed by immunofluorescence, RT-PCR and western blot analysis. FLT uptake value also exhibited a highly significant positive correlation with the Ki-67 index (r = 0.59, P < 0.001). Kaplan-Meier analysis revealed that MSP58 expression has a significant prognostic ability for the overall survival time similar to that found in the uptake value of FLT-PET.",
            "output": [
                "Is expression of 58-kD Microspherule Protein ( MSP58 ) Highly Correlated with PET Imaging of Tumor Malignancy and Cell Proliferation in Glioma Patients?"
            ]
        },
        {
            "id": "task847-9c796269eb664475b57478cb8a58fedb",
            "input": "To investigate the relationship between gestational diabetes mellitus (GDM) and the usual intake of fatty acids and indices of dietary fat quality [the atherogenicity (AI) and thrombogenicity indices (TI), and the ratios of hypo-and hypercholesterolemic (hH), \u2211n-3/\u2211n-6, and polyunsaturated/saturated fatty acids (P:S)], during mid-pregnancy.', \"799 adult pregnant women living in Ribeir\u00e3o Preto, SP, Brazil were screened and accepted for this cross-sectional GDM study. The Multiple Source Method was used to estimate participants' usual diet, using two 24-hour dietary recalls during mid-pregnancy. Diagnosis of GDM was defined by the American Diabetes Association criteria of 2015. Logistic regression analysis were used to assess the association between GDM and dietary fat, adjusted for age, education, parity, gestational age at the time of the interview, pre-pregnancy and current BMI, prior GDM, family history of diabetes, smoking, physical activity, energy, fiber, and fatty acids.\", 'The mean (standard deviation) age of the women was 28 (5) years, and 19% had GDM. After multiple adjustments, inverse associations between the highest tertile of \u2211n-3 fatty acids intake [0.21 (0.08-0.56)], \u03b1-linolenic intake [0.15 (0.05-0.42)], and GDM were found. A positive association between GDM and the highest tertile of TI [2.66 (1.34-5.29)], and a negative association with the highest tertile of hH ratio [0.41 (0.22-0.77)], were observed. No association between GDM and other indices of dietary fat quality were found.",
            "output": [
                "Is indices of dietary fat quality during midpregnancy associated with gestational diabetes?"
            ]
        },
        {
            "id": "task847-ba67aedc0b204e7ba99eb19b4664d222",
            "input": "Dementia is a common feature of Parkinson's disease (PD), but the neuropathological changes associated with the development of Parkinson's disease dementia (PDD) are only partially understood. Mitochondrial dysfunction is a hallmark of PD but has not been studied in PDD.\", 'Molecular and biochemical approaches were used to study mitochondrial activity and quantity in postmortem prefrontal cortex tissue. Tissues from pathologically confirmed PD and PDD patients and from age-matched controls were used to analyze the activity of mitochondrial enzyme complex nicotinamide adenine dinucleotide:ubiquinone oxidoreductase, or complex I (the first enzyme in the mitochondrial respiratory chain), mitochondrial DNA levels, and the expression of mitochondrial proteins.', \"Complex I activity was significantly decreased (27% reduction; analysis of variance with Tukey's post hoc test; P\\u2009<\\u20090.05) in PDD patients, and mitochondrial DNA levels were also significantly decreased (18% reduction; Kruskal-Wallis analysis of variance with Dunn's multiple comparison test; P\\u2009<\\u20090.05) in PDD patients compared with controls, but neither was significantly reduced in PD patients. Overall, mitochondrial biogenesis was unaffected in PD or PDD, because the expression of mitochondrial proteins in patients was similar to that in controls.",
            "output": [
                "Is dementia in Parkinson 's disease associated with enhanced mitochondrial complex I deficiency?"
            ]
        },
        {
            "id": "task847-0990ccbc1d7b4303be942065214acdbb",
            "input": "Intestinal cells are constantly exposed to luminal toxins. In this study, we investigated the effect of cellular stress caused by valinomycin, which is structurally and functionally similar to the bacterial toxin cereulide, on quercetin metabolism and cellular localization in undifferentiated cells.', 'Coadministration of quercetin and valinomycin (50 \u03bcM quercetin/0.05 \u03bcM valinomycin) reduced intracellular reactive oxygen species content and increased cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) of Caco-2 cells compared to valinomycin-only (0.05 \u03bcM) treatment. Quercertin was effectively metabolized into methyl, glucuronide, and sulfate conjugates, which were mostly secreted into to the culture medium. Three different O-methylated quercetin isomers were detected. Two were exported from the cells and one remained intracellularly. Further, valinomycin caused an increase in the intracellular accumulation of O-methylated quercetin metabolites compared to cells treated only with quercetin. In valinomycin-untreated cells, quercetin and O-methylated quercetin metabolite were localized in the cell membrane, whereas valinomycin treatment resulted in their uptake by the cells.",
            "output": [
                "Does quercetin mitigate valinomycin-induced cellular stress via stress-induced metabolism and cell uptake?"
            ]
        },
        {
            "id": "task847-df125068851d4bbca429f9b2510eb052",
            "input": "Intimal hyperplasia is a common cause of many vasculopathies. There has been a recent surge of interest in the bromo and extra-terminal (BET) epigenetic \"readers\" including BRD4 since the serendipitous discovery of JQ1(+), an inhibitor specific to the seemingly undruggable BET bromodomains. The role of the BET family in the development of intimal hyperplasia is not known.', 'We investigated the effect of BET inhibition on intimal hyperplasia using a rat balloon angioplasty model.', 'While BRD4 was dramatically up-regulated in the rat and human hyperplastic neointima, blocking BET bromodomains with JQ1(+) diminished neointima in rats. Knocking down BRD4 with siRNA, or treatment with JQ1(+) but not the inactive enantiomer JQ1(-), abrogated platelet-derived growth factor (PDGF-BB)-stimulated proliferation and migration of primary rat aortic smooth muscle cells. This inhibitory effect of JQ1(+) was reproducible in primary human aortic smooth muscle cells. In human aortic endothelial cells, JQ1(+) prevented cytokine-induced apoptosis and impairment of cell migration. Furthermore, either BRD4 siRNA or JQ1(+) but not JQ1(-), substantially down-regulated PDGF receptor-\u03b1 which, in JQ1(+)-treated arteries versus vehicle control, was also reduced.",
            "output": [
                "Does bET Bromodomain Blockade mitigate Intimal Hyperplasia in Rat Carotid Arteries?"
            ]
        },
        {
            "id": "task847-c9c381ebfee8427badd6f20cd451fc74",
            "input": "For patients receiving endoscopic submucosal dissection (ESD), there is urgent need pertaining to the prevention of postoperative bleeding. We conducted a retrospective propensity score-matched study that evaluated whether pre-ESD gastric lavage prevents postoperative bleeding after ESD for gastric neoplasms.', 'From September 2002 to October 2015, the 760 consecutive patients receiving ESD for gastric neoplasm were enrolled and data regarding them were retrospectively analyzed. All patients received conventional preventive treatment against delayed bleeding after ESD, including the administration of proton pump inhibitor and preventive coagulation of visible vessels, at the end of the ESD procedure.', 'Pre-ESD risk factors for postoperative bleeding included tumor size and no gastric lavage. Using multivariate analysis tumor size >2.0 cm (HR 2.90, 95% CI 1.65-5.10, p = 0.0002) and no gastric lavage (HR 3.20, 95% CI 1.13-9.11, p = 0.029) were found to be independent risk factors. Next, we evaluated the effect of gastric lavage on the prevention of post-ESD bleeding using a propensity score-matching method. A total of 284 subjects (142 per group) were selected. Adjusted odds ratio of gastric lavage for post-ESD bleeding was 0.25 (95% CI 0.071-0.886, p = 0.032).",
            "output": [
                "Does pretreatment Gastric Lavage reduce Postoperative Bleeding after Endoscopic Submucosal Dissection for Gastric Neoplasms?"
            ]
        },
        {
            "id": "task847-11e0be2afdee4a5dba1ffe9c608ad31a",
            "input": "The influence of the endoscopist on the polyp detection rate (PDR) is underappreciated in clinical practice. Moreover, flat lesions or lesions of the proximal colon are more difficult to detect. Here, we evaluated the differences in the PDR and the characteristics of detected polyps according to the experience of the colonoscopist.', 'We collected data on 2,549 patients who underwent screening colonoscopy performed by three fellows. The PDR was calculated according to the percentage of patients who had at least one polyp (method A) and according to the percentage of detected lesions (method B). The primary outcome included the change in the PDR, and the secondary outcome included the change in the characteristics of the detected polyps with increasing experience of the colonoscopist.', 'No proportional correlation was found between the PDR and increasing experience in colonoscopy with method A; however, with method B, the PDR increased after 400 colonoscopies (p=0.0209). With method B, the detection rates of small polyps (<5 mm) (p=0.0015) and polyps in proximal sites (p=0.0050) increased after 300 colonoscopies.",
            "output": [
                "Does the Colonoscopist 's Expertise affect the Characteristics of Detected Polyps?"
            ]
        },
        {
            "id": "task847-358ead1e21484ae4883a2710507cc159",
            "input": "This study was to investigate whether the previously proposed link between Alzheimer's disease (AD) and decreased retinal nerve fiber layer thickness could be explained by the relationship between abnormal CSF profiles and optic nerve head characteristics, focusing on the influence of CSF tau protein on the lamina cribrosa (LC) thickness (LCT).\", 'A total of 44 eyes from 18 patients with AD and 26 healthy subjects were subjected to enhanced-depth-imaging volume scanning of the optic nerve using spectral-domain optical coherence tomography. The B-scan images were constructed three-dimensionally using maximum intensity projection (MIP), and the LCT was measured at three locations (superior midperipheral, midhorizontal, and inferior midperipheral) using the thin-slab MIP images. CSF levels of amyloid \u03b2 1-42 peptide, (A\u03b21-42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau181P) were measured from CSF samples of each subject. The relationship between the level of CSF proteins and the LCT was determined using linear regression and fractional polynomial analyses.', 'Univariate regression analysis revealed that higher CSF levels of T-tau (P\\u2009=\\u20090.004) and P-tau181P (P\\u2009=\\u20090.027), as well as a smaller central corneal thickness (P\\u2009=\\u20090.032), were significantly associated with a smaller LCT. Multivariate analysis indicated that only CSF T-tau (P\\u2009=\\u20090.041) was significantly associated with the LCT. The relationship was well explained by both linear regression (R(2)\\u2009=\\u20090.179, P\\u2009=\\u20090.004) and fractional polynomial analysis (R(2)\\u2009=\\u20090.275, P\\u2009=\\u20090.001). When we performed an assessment by linear regression with an indicator, the relationship was significant both in the healthy and AD groups, with a stronger correlation found in the healthy group (regression coefficients\\u2009=\\u2009-1.098 vs. -0.280, P\\u2009=\\u20090.018).",
            "output": [
                "Is increased CSF tau level correlated with decreased lamina cribrosa thickness?"
            ]
        },
        {
            "id": "task847-fec5b46e9963485c83e4abdd9d1950d9",
            "input": "Exposure to aeroallergens induces eosinophilic airway inflammation in patients with asthma and allergic airway diseases. The circulating number of eosinophils in peripheral blood is relatively small, leading us to hypothesize that bone marrow needs to be engaged quickly to meet the demands of the tissues.', 'To investigate the communication between the lungs and bone marrow, we used acute allergen exposure and airway inflammation models in mice. Gene-deficient mice and cytokine reporter mice as well as in\\xa0vitro cell culture models were used to dissect the mechanisms.', 'Na\u00efve BALB/c mice produced increased numbers of eosinophil precursors and mature eosinophils in the bone marrow when their airways were exposed to a common fungal allergen, Alternaria alternata. Expression of IL-5 and IL-33 increased rapidly in the lungs, but not in the bone marrow. Sera from allergen-exposed mice promoted eosinophilopoiesis in bone marrow cells from na\u00efve mice, which was blocked by anti-IL-5 antibody. Mice deficient in the IL-33 receptor ST2 (i.e., Il1rl1(-/-) mice) were unable to increase their serum levels of IL-5 and allergen-induced eosinophilopoiesis in the bone marrow after allergen exposure. Finally, group 2 innate lymphoid cells (ILC2s) in the lungs showed robust expression of IL-5 after Alternaria exposure.",
            "output": [
                "Does iL-33 mediate reactive eosinophilopoiesis in response to airborne allergen exposure?"
            ]
        },
        {
            "id": "task847-4bf33b83a7bb4d4293b8016429ebbc74",
            "input": "Understanding the underlying molecular mechanisms in burn wound progression is crucial to providing appropriate diagnoses and designing therapeutic regimens for burn patients. When inflammation becomes unregulated, recurrent, or excessive, it interferes with burn wound healing. Autophagy, which is a homeostatic and catabolic degradation process, was found to protect against ischemic injury, inflammatory diseases, and apoptosis in some cases. In the present study, we investigated whether far-infrared (FIR) could ameliorate burn wound progression and promote wound healing both in vitro and in a rat model of deep second-degree burn. We found that FIR induced autophagy in differentiated THP-1 cells (human monocytic cells differentiated to macrophages). Furthermore, FIR inhibited both the NLRP3 inflammasome and the production of IL-1\u03b2 in lipopolysaccharide-activated THP-1 macrophages. In addition, FIR induced the ubiquitination of ASC, which is the adaptor protein of the inflammasome, by increasing tumor necrosis factor receptor-associated factor 6 (TRAF6), which is a ubiquitin E3 ligase. Furthermore, the exposure to FIR then promoted the delivery of inflammasome to autophagosomes for degradation. In a rat burn model, FIR ameliorated burn-induced epidermal thickening, inflammatory cell infiltration, and loss of distinct collagen fibers. Moreover, FIR enhanced autophagy and suppressed the activity of the NLRP3 inflammasome in the rat skin tissue of the burn model. Based on these results, we suggest that FIR-regulated autophagy and inflammasomes will be important for the discovery of novel therapeutics to promote the healing of burn wounds.",
            "output": [
                "Does far-infrared promote burn wound healing by suppressing NLRP3 inflammasome caused by enhanced autophagy?"
            ]
        },
        {
            "id": "task847-1f133af62b8443bb98ece90ff24d698f",
            "input": "Capillary blood glucose measurements are regularly used for nursing home residents with diabetes. The usefulness of these measurements relies on clear indications for use, correct measurement techniques, proper documentation and clinical use of the resulting blood glucose values. The use of a regular, invasive procedure may also entail additional challenges in a population of older, multimorbid patients who often suffer from cognitive impairment or dementia. The aim of this study was to explore the perspectives of physicians, registered nurses and auxiliary nurses on the use, usefulness and potential challenges of using capillary blood glucose measurements in nursing homes, and the procedures for doing so.', \"This was a qualitative study that used three profession-specific focus group interviews. Interviews were transcribed in modified verbatim form and analysed in accordance with Malterud's principles of systematic text condensation. Five physicians, four registered nurses and three auxiliary nurses participated in the focus groups.\", 'All professional groups regarded capillary blood glucose measurements as a necessity in the management of diabetes, the physicians to ensure that the treatment is appropriate, and the nurses to be certain and assured about their caring decisions. Strict glycaemic control and excessive measurements were avoided in order to promote the well-being and safety of the residents. Sufficient knowledge of diabetes symptoms, equivalent practices for glucose measurement, and unambiguous documentation and communication of results were determined to be most helpful. However, all professional groups seldom involved the residents in managing their own measurements and stated that guidelines and training had been inconsistent or lacking.",
            "output": [
                "Try ' I to bother the residents too much ' - the use of capillary blood glucose measurements in nursing homes?"
            ]
        },
        {
            "id": "task847-4f6826de3b59463a84cbe524bf937c48",
            "input": "Deoxyribonucleic acid methylation is an important epigenetic modification that is frequently altered in cancer. Recent reports showed that the level of 5-hydroxymethylcytosine was altered in various types of cancers. The influence of deoxyribonucleic acid methylation in cervical squamous cell carcinoma is not fully understood. In this study, we investigated 5-hydroxymethylcytosine and ten-eleven translocation expression in cervical squamous cell carcinoma and whether they are associated with poor survival in cervical squamous cell carcinoma.', 'We detected the expression of 5-hydroxymethylcytosine, 5-methylcytosine and TET1/2/3 in 140 patients with cervical squamous cell carcinoma and 40 patients with normal cervical tissues by immunohistochemistry. We assessed the prognostic values of 5-hydroxymethylcytosine, 5-methylcytosine and TET2 in the clinical outcome of cervical squamous cell carcinoma.', 'Expression of 5-hydroxymethylcytosine was significantly decreased in cervical squamous cell carcinoma compared with normal cervix tissues. In contrast, 5-methylcytosine expression was significantly increased in cervical squamous cell carcinoma compared with normal cervix tissues. Moreover, expression of TET2, but not TET1 and TET3, was decreased in cervical squamous cell carcinoma. Our study showed that the decreased level of 5-hydroxymethylcytosine predicts poor prognosis of cervical squamous cell carcinoma patients. The expression of 5-hydroxymethylcytosine was an independent prognostic factor for both disease-free and overall survival of cervical squamous cell carcinoma patients.",
            "output": [
                "Is 5-Hydroxymethylcytosine expression associated with poor survival in cervical squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-99732597581e45459c01a6873db57bbe",
            "input": "Human epidermis provides the body a barrier against environmental assaults. To assume this function, the epidermis needs the renewal of keratinocytes allowed by constant mitosis, which replace the exfoliating corneocytes. Keratinocyte stem cells (KSCs) located in the basal epidermis are mitotically active, self-renewing and govern the epithelial stratification by producing renewed source of keratinocytes. Protein complex such as the chromosomal passenger complex (CPC) allows the correct development of this process. The CPC is composed of four members: INCENP, survivin, borealin and aurora kinase B, and the disruption of the CPC during cell division induces mitotic spindle defects and improper repartition of chromosomes. The aim of our study was to investigate the implication of CRM1 and survivin in the progress of mitosis in skin keratinocytes.', 'Cultured human keratinocytes and skin biopsies were used in this study. KSCs-enriched population of keratinocytes was isolated from total keratinocytes by differential attachment to a type IV collagen matrix. Survivin and CRM1 expression levels were assessed by immunofluorescence and immunoblotting. Specific siRNAs for each CPC member and for CRM1 were used to determine the relationship between these proteins. Survivin-specific siRNA was used to induce the apparition of mitotic abnormalities in cultured keratinocytes.', \"We demonstrated the ability of our compound 'IV08.009' to modulate the expression level of survivin and CRM1 in keratinocytes and in skin biopsies. We observed that members of the CPC are interdependent: siRNA-induced inhibition of one component caused a decrease in the expression of all other CPC members. Downregulation of survivin or CRM1 induced mitotic abnormalities in keratinocytes. However, decreased number of mitotic abnormalities was observed in keratinocytes after 'IV08.009' application.",
            "output": [
                "Are cRM1 and chromosomal passenger complex component survivin essential to normal mitosis progress and to preserve keratinocytes from mitotic abnormalities?"
            ]
        },
        {
            "id": "task847-4377be86599b4d86b48c4255596ee16e",
            "input": "High arginase-1 (Arg) expression by myeloid-derived suppressor cells (MDSC) is known to inhibit antitumor T-cell responses through depletion of l-arginine. We have previously shown that nitric oxide (NO), an immune mediator produced from l-arginine, is a potent radiosensitizer of hypoxic tumor cells. This study therefore examines whether Arg(+) overexpressing MDSC may confer radioresistance through depleting the substrate for NO synthesis.', 'MDSC and Arg expression were studied in preclinical mouse CT26 and 4T1 tumor models and further validated in rectal cancer patients in comparison with healthy donors. The radioprotective effect of MDSC was analyzed in hypoxic tumor cells with regard to l-arginine depletion.', 'In both mouse tumors and cancer patients, MDSC expansion was associated with Arg activation causing accelerated l-arginine consumption. l-Arginine depletion in turn profoundly suppressed the capacity of classically activated macrophages to synthesize NO resulting in impaired tumor cell radiosensitivity. In advanced cT3-4 rectal cancer, circulating neutrophils revealed Arg overexpression approaching that in MDSC, therefore mounting a protumor compartment wherein Arg(+) neutrophils increased from 17% to over 90%.",
            "output": [
                "Do myeloid-derived suppressor cells reveal radioprotective properties through arginase-induced l-arginine depletion?"
            ]
        },
        {
            "id": "task847-8bc7a41b690146a29cd9008cab5fc34b",
            "input": "The establishment of accurate equations for glomerular filtration rate (GFR) estimations is still far from the realization. Factors such as age, diabetes, stage of CKD, pregnancy, muscle mass and ethic nation are associated with less reliance upon commonly utilized estimation equations. We aimed to compare the routine use of 24-hour creatinine clearance (CrCl) and GFR estimates calculated by Crockoft-Gault (CG) and modification of diet in renal disease (MDRD) formulas in patients with different levels of renal dysfunction in subgroups, based on Body Mass Index (BMI) and serum albumin (Alb) levels.', 'Two hundred and seventy-nine non diabetic patients (172 men and 107 women), aged 54\u00b123 years, with BMI 27.3\u00b14.4 were enrolled in the study. All patients presented creatinine 1.8\u00b11.2 (mg/dL) and Alb 3.5\u00b11.3g/dL. The comparison of CrCl versus CG had bias 3.1 while the comparison of CrCl versus MDRD had a bias of 6.6.', 'Univariate analysis showed that age, sex and BMI were not significant biases related to the CG, MDRD and CrCl. Indeed, the bias related to the CG was significantly lower than that related to MDRD in patients with either low or high serum albumin. Interestingly, the bias associated with CG was 1.3 in non-diabetic patients with Alb \u22643.5 mg /dL suggesting that CG equation could be used interchangeable to CrCl in these patients.",
            "output": [
                "Does comparison of creatinine clearance estimate in subgroups based on Body Mass Index and albumin?"
            ]
        },
        {
            "id": "task847-c9b446aa543f488783a662e897c6a310",
            "input": "Fatigue is likely to be an important limiting factor in adolescents with spastic cerebral palsy (CP).', 'To determine the effects of walking-induced fatigue on postural control adjustments in adolescents with unilateral CP and their typically developing (TD) peers.', 'Ten adolescents with CP (14.2 \u00b1 1.7 yr) and 10 age-, weight- and height-matched TD adolescents (14.1 \u00b1 1.9 yr) walked for 15 min on a treadmill at their preferred walking speed. Before and after this task, voluntary strength capacity of knee extensors (MVC) and postural control were evaluated in 3 conditions: eyes open (EO), eyes closed (EC) and with dual cognitive task (EODT).', 'After walking, MVC decreased significantly in CP (-11%, P<0.05) but not in TD. The CoP area was only significantly increased in CP (90%, 34% and 60% for EO, EC and EODT conditions, respectively). The CoP length was significantly increased in the EO condition in CP and TD (20% and 21%) and was significantly increased in the EODT condition by 18% in CP only.",
            "output": [
                "Does walking-induced muscle fatigue impair postural control in adolescents with unilateral spastic cerebral palsy?"
            ]
        },
        {
            "id": "task847-7cd126e4b8e9456783015a8b456e5b96",
            "input": "Cardiac transplantation is the only curative therapy for end-stage heart failure. Fibrosis is one of the major causes for impaired function of cardiac allografts. MicroRNAs, a class of small non-coding RNAs, play a critical role in the development of cardiovascular disease, but the role of microRNAs in cardiac allograft failure is not well understood.', 'To uncover a role of microRNAs during cardiac graft fibrosis, we generated global microRNA profiles in allogeneic (BALB/c in C57BL/6N) and isogeneic (C57BL/6N in C57BL/6N) murine hearts after transplantation. miR-21 together with cardiac fibrosis was increased in cardiac allografts compared with isografts. Likewise, patients with cardiac rejection after heart transplantation showed increased cardiac miR-21 levels. miR-21 was induced upon treatment with IL-6 in a monocyte cell line. Overexpression of miR-21 in this monocyte cell line activated a fibrotic gene programme and promoted monocyte-to-fibrocyte transition together with activation of chemokine (C-C) motif ligand 2 (monocyte chemoattractant protein 1) via the phosphatase and tensin homologue/activator protein 1 regulatory axis. In vivo, both genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in cardiac allografts.",
            "output": [
                "Does miR-21 promote fibrosis in an acute cardiac allograft transplantation model?"
            ]
        },
        {
            "id": "task847-92029096e61a4a2ab599ea037f85cab7",
            "input": "Gastroesophageal reflux disease (GERD) with proton pump inhibitor (PPI) use is associated with an increased risk of osteoporosis. The risk of hip fracture is not increased in GERD patients with PPI use.', 'The relationship between GERD with PPI treatment and the risk of osteoporosis is unclear. We aimed to determine the risk of developing osteoporosis in patients diagnosed with GERD.', 'Patients diagnosed with GERD and received PPI treatment between 2000 and 2010 were identified from the Longitudinal Health Insurance Database as the study cohort (n\\u2009=\\u200910,620), which was frequency matched with the comparison cohort (n\\u2009=\\u200920,738) sampled from the general population according to age, sex, index year, and comorbidities. Both cohorts were followed until the end of 2011. The risk of osteoporosis was evaluated in both groups by using Cox proportional hazards regression models.', 'The GERD patients with PPI treatment had a greater incidence (31.4 vs 20.7 per 1000 person-year; crude hazard ratio [cHR] 1.51; 95\\xa0% confidence interval [CI] 1.40-1.63) and a higher risk (adjusted HR [aHR] 1.50; 95\\xa0% CI 1.39-1.62) of osteoporosis than that of the comparison cohort. However, the overall incidence of hip fracture was not different between the GERD with PPI use and the control cohorts (aHR 0.79; 95\\xa0% CI 0.53-1.18).",
            "output": [
                "Is gastroesophageal reflux disease with proton pump inhibitor use associated with an increased risk of osteoporosis : a nationwide population-based analysis?"
            ]
        },
        {
            "id": "task847-6697440ff5c24e8ab846f75943b61927",
            "input": "The significance of bile duct injury and ductular reaction in biopsies from autoimmune hepatitis patients is not clear. We aim to establish the prevalence and clinical relevance of both phenomena in autoimmune hepatitis.', 'Cases of newly diagnosed, untreated autoimmune hepatitis without overlap syndrome were selected. Pretreatment and follow up biopsies were scored for inflammation, fibrosis, bile ductal injury and ductular reaction.', 'Thirty-five cases were studied of whom 14 cases had follow up biopsies. Bile duct injury was present in 29 cases (83%), mostly in a PBC-like pattern and was not correlated with demographical or laboratory findings. Ductular reaction, observed in 25 of 35 cases (71%) using conventional histology and in 30 of 32 cases (94%) using immunohistochemistry, was correlated with portal and lobular inflammation, interface hepatitis and centrilobular necrosis as well as bile duct injury and fibrosis. In 11 of 14 cases (79%) ductular reaction remained present on post-treatment biopsy whereas bile duct injury persisted in six of 14 (43%) of cases.",
            "output": [
                "Are bile ductal injury and ductular reaction frequent phenomena with different significance in autoimmune hepatitis?"
            ]
        },
        {
            "id": "task847-470801e721154be1a1f4073b1b85ced1",
            "input": "The aims of this study were to test the hypothesis that short-term high salt intake reduces macrovascular and microvascular endothelial function in the absence of changes in blood pressure and to determine whether acute exercise restores endothelial function after high salt in women.', 'Twelve women were administered high salt (11\\u200ag of sodium chloride for 7 days) and then underwent a weightlifting session. Brachial artery flow-mediated dilation and nitroglycerin dilation were measured with ultrasound at baseline, after high salt, and after weightlifting. Subcutaneous fat tissue biopsies were obtained at baseline, after high salt, and after weightlifting. Resistance arteries from biopsies were cannulated for vascular reactivity measurements in response to flow [flow-induced dilation (FID)] and acetylcholine.', 'Blood pressure was similar before and after high salt diet. Brachial flow-mediated dilation was reduced after high salt diet but was not affected by acute weightlifting. Brachial nitroglycerin dilations were similar before and after high salt. FID and acetylcholine-induced dilation of resistance arteries were similar to that of before and after high salt diet. FID and acetylcholine-induced dilation was not altered by weightlifting after high salt diet. However, N-nitro-L-arginine methyl ester significantly reduced FID at baseline and after exercise but had no effect dilator reactivity after high salt diet alone.",
            "output": [
                "Does short-term high salt intake reduce brachial artery and microvascular function in the absence of changes in blood pressure?"
            ]
        },
        {
            "id": "task847-88b75477942341279d9f755eb21f3f75",
            "input": "Secreted frizzled-related protein-1 (SFRP1) is a well-known inhibitor of the wingless type (WNT)-\u03b2-catenin signaling pathway and its inactivation plays an important role in the development and progression of various types of cancer. However, the clinical significance of SFRP1 expression in patients with hepatocellular carcinoma (HCC) remains unknown.', 'A total of 63 patients with HCC who underwent hepatectomy at our Institution were enrolled in this study. A quantitative real-time polymerase chain reaction (RT-PCR) was performed to determine the SFRP1 mRNA expression level in both the tumorous and non-tumorous tissues of HCC. The patients were divided into low and high gene-expression groups based on the SFRP1 gene expression level in their tumor tissues. We analyzed the differences in clinicopathological characteristics between these two groups of patients.', 'The expression level of SFRP1 was significantly lower in tumor tissue than in non-tumor tissue (p<0.0001). Significant correlations were observed between a high expression of SFRP1 in tumor tissue and older than 65 years (p=0.030), tumor size less than 5 cm (p=0.011); and no vascular invasion (p=0.004). Patients with high SFRP1 expression in tumor tissue had a significantly better overall survival rate (p=0.040). However, the SFRP1 expression level was not defined as an independent risk factor for patient survival based on results of multivariate analysis.",
            "output": [
                "Does loss of SFRP1 Expression be Associated with Poor Prognosis in Hepatocellular Carcinoma?"
            ]
        },
        {
            "id": "task847-ff7ce0855dc141f2b180676aabd04811",
            "input": "Women diagnosed with pregnancy-associated breast cancer postpartum have a worse prognosis, stage for stage, than other women with breast cancer. The time of breast involution is tumor promotional. The extracellular matrix protein tenascin-C is upregulated during involution in animal models and promotes breast cancer progression. It interacts with transforming growth factor (TGF)\u03b2, which also is involved in breast involution and breast cancer progression. Little is known about the expression of tenascin-C during human breast involution, nor its relationship to TGF\u03b2. The purpose of this study was to investigate the expression of tenascin-C throughout lactation, as well as its relationship to TGF\u03b21 and TGF\u03b22.', 'Three milk samples from 25 lactating women (transitional, whole, and wean) were collected, separated into components (cells, fat, and skim), and the skim fraction analyzed for total protein, tenascin-C, TGF\u03b21, and TGF\u03b22. Tenascin-C, TGF\u03b21, and TGF\u03b22 were detectable in all milk samples.', 'Highest tenascin-C levels on average were found in whole milk, whereas highest mean TGF\u03b21 and TGF\u03b22 levels were in wean milk. Wean samples on average had higher levels of both TGF\u03b21 (26%) and TGF\u03b22 (>500%) than matched transitional milk samples. Tenascin-C levels in wean milk were associated with nursing length (p = 0.048). Combining all three milk collection time points, tenascin-C exhibited a weak inverse correlation with TGF\u03b21 and TGF\u03b22 (p < 0.1). The inverse correlation at the wean time point was stronger for TGF\u03b22 than -1 (-0.37 versus -0.25). Tenascin-C, a protein known to promote breast cancer progression, is expressed throughout lactation.",
            "output": [
                "Does expression of the Extracellular Matrix Protein Tenascin-C vary During Lactation?"
            ]
        },
        {
            "id": "task847-e671f665d7b44ac1bfe0a60a84ec4959",
            "input": "Essentials The procoagulant effects of microparticles (MPs) on coagulation in endotoxemia are not known. MPs from endotoxemia volunteers were evaluated for procoagulant activity in a plasma milieu. MPs from endotoxemia volunteers shortened clotting times and enhanced thrombin generation. MP procoagulant effects were mediated in a factor XI-dependent manner.",
            "output": [
                "Do procoagulant microparticles promote coagulation in a factor XI-dependent manner in human endotoxemia?"
            ]
        },
        {
            "id": "task847-13f7dfef09fa471eaefcf33b647e53a6",
            "input": "The objective of this study was to increase the spatial and temporal resolution of dynamic 3-dimensional (3D) magnetic resonance imaging (MRI) of lung volumes and diaphragm motion. To achieve this goal, we evaluate the utility of the proposed blind compressed sensing (BCS) algorithm to recover data from highly undersampled measurements.', 'We evaluated the performance of the BCS scheme to recover dynamic data sets from retrospectively and prospectively undersampled measurements. We also compared its performance against that of view-sharing, the nuclear norm minimization scheme, and the l1 Fourier sparsity regularization scheme. Quantitative experiments were performed on a healthy subject using a fully sampled 2D data set with uniform radial sampling, which was retrospectively undersampled with 16 radial spokes per frame to correspond to an undersampling factor of 8. The images obtained from the 4 reconstruction schemes were compared with the fully sampled data using mean square error and normalized high-frequency error metrics. The schemes were also compared using prospective 3D data acquired on a Siemens 3 T TIM TRIO MRI scanner on 8 healthy subjects during free breathing. Two expert cardiothoracic radiologists (R1 and R2) qualitatively evaluated the reconstructed 3D data sets using a 5-point scale (0-4) on the basis of spatial resolution, temporal resolution, and presence of aliasing artifacts.', 'The BCS scheme gives better reconstructions (mean square error = 0.0232 and normalized high frequency = 0.133) than the other schemes in the 2D retrospective undersampling experiments, producing minimally distorted reconstructions up to an acceleration factor of 8 (16 radial spokes per frame). The prospective 3D experiments show that the BCS scheme provides visually improved reconstructions than the other schemes do. The BCS scheme provides improved qualitative scores over nuclear norm and l1 Fourier sparsity regularization schemes in the temporal blurring and spatial blurring categories. The qualitative scores for aliasing artifacts in the images reconstructed by nuclear norm scheme and BCS scheme are comparable.The comparisons of the tidal volume changes also show that the BCS scheme has less temporal blurring as compared with the nuclear norm minimization scheme and the l1 Fourier sparsity regularization scheme. The minute ventilation estimated by BCS for tidal breathing in supine position (4 L/min) and the measured supine inspiratory capacity (1.5 L) is in good correlation with the literature. The improved performance of BCS can be explained by its ability to efficiently adapt to the data, thus providing a richer representation of the signal.",
            "output": [
                "Does blind Compressed Sensing enable 3-Dimensional Dynamic Free Breathing Magnetic Resonance Imaging of Lung Volumes and Diaphragm Motion?"
            ]
        },
        {
            "id": "task847-1fe1edfef1d74b8f988bf087fe3ec2d3",
            "input": "Fructose may play a crucial role in the pathogenesis of metabolic syndrome (MetS). However, the pathogenic mechanism of the fructose-induced MetS has not yet been investigated fully. Recently, several reports have investigated the association between mitochondrial DNA (mtDNA) and MetS. We examined the effect of fructose-rich diets on mtDNA content, transcription, and epigenetic changes.', 'Four-week-old male Sprague-Dawley rats were offered a 20% fructose solution for 14weeks. We quantified mRNAs for hepatic mitochondrial genes and analyzed the mtDNA methylation (5-mC and 5-hmC) levels using ELISA kits.', 'Histological analysis revealed non-alcoholic fatty liver disease (NAFLD) in fructose-fed rats. Hepatic mtDNA content and transcription were higher in fructose-fed rats than in the control group. Global hypomethylation of mtDNA was also observed in fructose-fed rats.",
            "output": [
                "Does fructose consumption induce hypomethylation of hepatic mitochondrial DNA in rats?"
            ]
        },
        {
            "id": "task847-a85346d53aed4ac98cd4800a1f6ef187",
            "input": "Clostridium acetobutylicum is one of the most important butanol producing strains. However, environmental stress in the fermentation process usually leads to a lower yield, seriously hampering its industrialization. In order to systematically investigate the key intracellular metabolites that influence the strain growth and butanol production, and find out the critical regulation nodes, an integrated analysis approach has been carried out in this study.', 'Based on the gas chromatography-mass spectrometry technology, the partial least square discriminant analysis and the pathway analysis, 40 metabolic pathways linked with 43 key metabolic nodes were identified. In-depth analysis showed that lots of amino acids metabolism promoted cell growth but exerted slight influence on butanol production, while sugar metabolism was favorable for cell growth but unfavorable for butanol synthesis. Besides, both lysine and succinic acid metabolism generated a complex effect on the whole metabolic network. Dicarboxylate metabolism exerted an indispensable role on cell growth and butanol production. Subsequently, rational feeding strategies were proposed to verify these conclusions and facilitate the butanol biosynthesis. Feeding amino acids, especially glycine and serine, could obviously improve cell growth while yeast extract, citric acid and ethylene glycol could significantly enhance both growth and butanol production.",
            "output": [
                "Do integrated intracellular metabolic profiling and pathway analysis approaches reveal complex metabolic regulation by Clostridium acetobutylicum?"
            ]
        },
        {
            "id": "task847-cd4c292946354350ab5d3d94271ee98a",
            "input": "Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. Although a majority of patients remain asymptomatic, complications may occur in a subset of patients. MD is a rare cause of gastrointestinal bleeding (GIB) in adults. We aimed to clarify the possible role of capsule endoscopy (CE) in the identification of Meckel's diverticulum.\", 'From October 2004 to December 2010, 157 CEs were performed (83 male individuals, mean age 51\u00b120 years; range 3-83 years) for obscure GIB. Before CE, all patients underwent nonconclusive upper and lower endoscopy at least two times and barium follow-through.', 'CE identified the source of bleeding in 70/157 patients (44.6%). MD was diagnosed in 13/70 (18.6%) patients (11 male individuals, mean age 35\u00b120 years, range, 3-69 years) after CE. Nine patients presented with obscure overt and four with obscure occult bleeding. The mean duration of obscure GIB history was 13 months (range 1-72 months). The mean hemoglobin concentration at the time of the procedure was 115\u00b112\\u2009g/l. The findings of MD on CE were double lumen sign (13/13), visible blood (7/13), and diaphragm sign (6/13). All patients were operated upon, and MD histologically verified in 11. In two patients CE was false-positive and in two patients, false-negative. Capsule endoscopy had a positive predictive value of 84.6% for the diagnosis of MD.",
            "output": [
                "Is capsule endoscopy useful diagnostic tool for diagnosing Meckel 's diverticulum?"
            ]
        },
        {
            "id": "task847-d10b9518f60d428c8e6c06e4c4d02c10",
            "input": "Severity of rheumatoid arthritis and progression of radiographic joint damage have decreased over the last decades.', 'To examine whether this trend is attributable to an underlying trend towards milder disease or to improved treatment.', 'The study used an inception cohort of patients with early rheumatoid arthritis seen at the Wichita Arthritis Center, Wichita, Kansas, USA, since 1973 and monitored prospectively since their first clinic visit through clinical, radiographic, laboratory, demographic and self-reported data. The radiographic disease progression in patients with disease onset in the 1970s, 1980s and 1990s was compared using a multivariate regression model for longitudinal data. The analysis was adjusted for differences in baseline predictors, type of disease-modifying antirheumatic drugs (DMARDs) and steroid use.', '418 patients with rheumatoid arthritis with radiographic follow-up were included. Patients in earlier decades used fewer DMARDs, had longer disease durations and higher tender joint counts at their first visit. Other important predictors of disease progression did not differ significantly between decades of disease onset. The unadjusted rates of radiographic progression differed between decades (analysis of variance, p = 0.01), with a significant trend towards less radiographic progression in more recent times (trend, p<0.001). However, after adjusting for DMARD use, steroid use and baseline predictors, differences between decades vanished (analysis of variance, p = 0.40) and the trend towards less radiographic progression disappeared (trend, p = 0.45).",
            "output": [
                "Are progression of radiographic joint damage in different eras : trends towards milder disease in rheumatoid arthritis attributable to improved treatment?"
            ]
        },
        {
            "id": "task847-5573556e89fb4f1bb2f6b4e5e91f3105",
            "input": "To study the presence of citrullinated proteins in inflammatory conditions and in clinically non-affected tissues of controls.', 'Synovial biopsy specimens from 19 patients with rheumatoid arthritis and 10 healthy controls were investigated by immunohistochemistry. Additionally, muscle tissue from 5 patients with polymyositis and from 7 healthy controls, intestinal tissue from macroscopically affected and non-affected areas from 10 patients with inflammatory bowel disease (IBD) and tonsil tissues from 4 chronically inflamed tonsils were studied.', 'Citrullinated proteins were present in all synovial biopsy specimens from patients with rheumatoid arthritis, whereas only three of 10 healthy synovial biopsy specimens showed scarce amounts of citrullination. Citrullination was also present in all myositis-affected muscles, whereas it was absent in the muscle tissues of controls. All tonsil biopsy specimens studied were positive for citrulline. Even though more frequently detected in the macroscopically affected colonic areas, no marked difference was observed in the pattern or extent of citrullination between the macroscopically affected and non-affected intestinal IBD tissues.",
            "output": [
                "Is citrullination an inflammation-dependent process?"
            ]
        },
        {
            "id": "task847-1192770d7d4046bba8949fe8482290e6",
            "input": "The administration of anabolic-androgenic steroids (AAS) to improve athletic performance has increased notably during the past three decades, even among nonathletes. Thyroid function is affected by AAS use in humans, although the mechanisms of the effects of AAS are unclear. We evaluated the effects on thyroid function of supraphysiologic doses of nandrolone decanoate (DECA), which is one of the most anabolic-androgenic steroids (AAS) used.', 'Male Wistar rats were treated with vehicle or 1 mg.100 g(-1) body weight (b.w.) of DECA, once a week for 8 wk, intramuscularly. We analyzed thyroperoxidase (TPO) activity, type 1 iodothyronine deiodinase (D1) activities in liver, kidney, pituitary, and thyroid, and serum levels of total T3, total T4, free T4, and TSH. Parametric and nonparametric t-tests were employed for statistical analyses.', 'Treated animals showed a significant increase in the weight of kidneys and heart, and a decrease in the relative testis weight. Retroperitoneal adipose tissue was only slightly decreased. DECA treatment induced a significant increase in the absolute and relative thyroid gland weight. The concentrations of total serum T3, free T4, and TSH decreased significantly with treatment, but total serum T4 levels were unchanged. Thyroperoxidase activity was unaltered, whereas liver and kidney D1 activities were significantly increased, but pituitary and thyroid D1 did not change.",
            "output": [
                "Does chronic administration of anabolic androgenic steroid alter murine thyroid function?"
            ]
        },
        {
            "id": "task847-3bb74098f7ae4164b7a1924c2b046e89",
            "input": "To determine the efficacy of the National Athletic Trainers' Association Board of Certification (NATABOC) clinical experience requirements and individual student characteristics to predict candidate outcomes on the NATABOC certification examination.\", 'For all subjects, we gathered survey information and examination scores. The survey information included age, sex, route to certification, previous athletic training and allied health experience, and clinical education experiences.', 'A total of 269 subjects, 22.25% of all first-time candidates for the June and November 1993 NATABOC examinations, were included in this study.', 'Data were analyzed for standard descriptive statistics and parametric linear regression and correlational relationships.', 'Total clinical hours, high-risk sport experiences, and previous athletic training experience were not predictive of examination outcomes. Although our results indicated a relationship between previous allied health experience and both outcome on the written section of the examination and age and outcome on the oral/practical section, these characteristics also were not predictive of examination outcomes.",
            "output": [
                "Are clinical Experiences Predictive of Outcomes on the NATABOC Examination?"
            ]
        },
        {
            "id": "task847-09a15c051d5c4d9fa297e766d27a16fe",
            "input": "To determine the effect of the Breathe Right (BR) external nasal dilator strip on treadmill exercise performed while wearing an upper maxillary mouthguard.', 'Two-way repeated-measures design with subjects acting as their own controls. Subjects performed 2 randomly assigned bouts of incremental treadmill exercise (with and without the BR strip) while wearing upper maxillary mouthguards.', 'Nineteen young, healthy, recreationally active men.', 'we assessed subjective nasal patency levels at rest. We also recorded heart rate, dyspnea rating, and treadmill speed at 2 submaximal exercise levels and at volitional fatigue.', 'Subjective nasal patency was significantly increased with the strip. Repeated-measures analyses of variance revealed a significant main effect of the BR strip on dyspnea ratings during exercise, but there was no effect of the strip on test duration, heart rate, or running speed during the tests.",
            "output": [
                "Do external nasal dilator strips affect treadmill performance in subjects wearing mouthguards?"
            ]
        },
        {
            "id": "task847-e879baaa860948abacc0c61c076319a8",
            "input": "12/15 lipoxygenase (12/15LO) has been implicated as a mediator of inflammation and atherosclerosis. In the current study, we identified mechanisms through which 12/15LO mediates monocyte:endothelial interactions in vivo in apolipoprotein E-deficient mice (apoEKO), a well-characterized mouse model of atherosclerosis.', 'In apoEKO mice that are also deficient in 12/15LO (doubleKO), monocyte adhesion to aorta in vivo was reduced by 95% in doubleKO mice compared with apoEKO mice. Inhibition of 12/15LO in apoEKO mice in vivo using CDC (Cinnamyl-3,4-Dihydroxy-a-Cyanocinnamate) prevented monocyte adhesion to aortic endothelium in apoEKO mice. Aortic endothelium of apoEKO mice had significant activation of rhoA compared with doubleKO aortic endothelium. Further, apoEKO aorta displayed significant activation of NF-kappaB. DoubleKO aorta displayed little nuclear localization of NF-kappaB. Finally, we found significant upregulation of intercellular adhesion molecule-1 (ICAM-1) on apoEKO aortic endothelium compared with doubleKO endothelium. Inhibition of rhoA and PKCalpha significantly reduced NF-kappaB activation, ICAM-1 induction, and monocyte adhesion to aorta.",
            "output": [
                "Does 12/15 lipoxygenase mediate monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of RhoA and NF-kappaB?"
            ]
        },
        {
            "id": "task847-e1bbd619a8ec4de9a75a44568d80d2c7",
            "input": "Pineal function has been considered particularly as a neuroendocrine modulator in hormone responsive tumors, like the hormone-dependent mammary tumors. The complexity of the gland function, moreover, is denoted by the presence of a local renin-angiotensin-system (RAS) that regulates melatonin biosynthesis. Classically, angiotensin II (Ang II) has been considered as the effector peptide of the RAS, but Ang II is not the only active peptide. Several of its degradation products, including angiotensin III (Ang III) and angiotensin IV (Ang IV) also possess biological functions. These peptides are formed via the activity of several aminopeptidases. Our aim is to know their role in the regulation of pineal RAS and breast cancer.', 'Aminopeptidase N (APN), aminopeptidase B (APB) and aminopeptidase A (aspartyl- and glutamyl-aminopeptidase, APA) activities are measured in the pineal gland of rats with breast cancer induced by N-methyl nitrosourea (NMU).', 'Aminopeptidase activities were measured fluorimetrically using their corresponding aminoacyl-beta-naphthylamides as substrates.', 'Specific APN and APB activities in pineal gland of controls and NMU-treated rats were not modified. Aspartyl aminopeptidase activity significantly decreased in NMU-treated rats when compared with control group. On the contrary, glutamyl aminopeptidase activity did not show significant differences between groups.",
            "output": [
                "Are renin-angiotensin system-regulating aminopeptidase activities modified in the pineal gland of rats with breast cancer induced by N-methyl-nitrosourea?"
            ]
        },
        {
            "id": "task847-74bc24fc94d64d33a843bca098e0b0eb",
            "input": "Interobserver and intraobserver reliability study of improved method to evaluate radiographs of patients with scoliosis.', 'To determine the reliability of a computer-assisted measurement protocol for evaluating Cobb angle and King et al classification.', 'Evaluation of scoliosis radiographs is inherently unreliable because of technical and human judgmental errors. Objective, computer-assisted evaluation tools may improve reliability.', 'Posteroanterior preoperative radiographic images of 27 patients with adolescent idiopathic scoliosis were each displayed on a computer screen. They were marked 3 times in random sequence by each of 5 evaluators (observers) who marked 70 standardized points on the vertebrae and sacrum in each radiograph. A computer program (Spine 2002;27:2801-5) that identified curves, calculated Cobb angles, and generated the King et al classification automatically analyzed coordinates of these points. The interobserver and intraobserver variability of the Cobb angle and King et al classification evaluations were quantified and compared with values obtained by unassisted observers.', 'Average Cobb angle intraobserver standard deviation was 2.0 degrees for both the thoracic and lumbar curves (range 0.1 to 8.3 degrees for different curves). Interobserver reliability was 2.5 degrees for thoracic curves and 2.6 degrees for lumbar curves. Among the 5 observers, there was an inverse relationship between repeatability and time spent marking images, and no correlation with image quality or curve magnitude. Kappa values for the variability of the King et al classification averaged 0.85 (intraobserver).",
            "output": [
                "Do computer-assisted algorithms improve reliability of King classification and Cobb angle measurement of scoliosis?"
            ]
        },
        {
            "id": "task847-b5df0fc9ecae4b06a780e317be35d67e",
            "input": "A comparative study.', 'To investigate sitting postures of asymptomatic individuals and nonspecific chronic low back pain (NS-CLBP) patients (pooled and subclassified) and evaluate the importance of subclassification.', 'Currently, little evidence exists to support the hypothesis that CLBP patients sit differently from pain-free controls. Although classifying NS-CLBP patients into homogeneous subgroups has been previously emphasized, no attempts have been made to consider such groupings when examining seated posture.', 'Three angles (sacral tilt, lower lumbar, and upper lumbar) were measured during \"usual\" and \"slumped\" sitting in 33 NS-CLBP patients and 34 asymptomatic subjects using an electromagnetic measurement device. Before testing, NS-CLBP patients were subclassified by two blinded clinicians. Twenty patients were classified with a flexion motor control impairment and 13 with an active extension motor control impairment.', 'No differences were found between control and NS-CLBP (pooled) patients during usual sitting. In contrast, analyses based on subclassification revealed that patients classified with an active extension pattern sat more lordotic at the symptomatic lower lumbar spine, whereas patients with a flexion pattern sat more kyphotic, when compared with healthy controls (F = 19.7; df1 = 2, df2 = 63, P < 0.001). Further, NS-CLBP patients had less ability to change their posture when asked to slump from usual sitting (t = 4.2, df = 65; P < 0.001).",
            "output": [
                "Are differences in sitting postures associated with nonspecific chronic low back pain disorders when patients are subclassified?"
            ]
        },
        {
            "id": "task847-90c5d71962604cecb4f3fa7432f3ce41",
            "input": "Prospective, population-based cohort study.', 'To examine whether worker demographic, pain, disability, and psychosocial variables, assessed soon after work-related back pain disability onset, predict 6-month work disability.', 'Greater age, pain, and physical disability, and certain psychosocial characteristics may be risk factors for prolonged back pain-related work disability, although many studies have been small, findings have been inconsistent, and some psychosocial variables have not been examined prospectively.', \"Workers (N = 1,068) completed telephone interviews assessing demographic, pain, disability, and psychosocial variables 18 days (median) after submitting Workers' Compensation back pain disability claims. Administrative measures of work disability 6 months after claim submission were obtained.\", 'At 6 months, 196 workers (18.4%) were receiving work disability compensation. Age, race, education, and baseline pain and disability were significant predictors of 6-month disability. Adjusting for baseline demographics, pain, disability, and other psychosocial variables, high work fear-avoidance (odds ratio, 4.6; 95% confidence interval, 1.6-13.7) and very low recovery expectations (odds ratio, 3.1, 95% confidence interval, 1.5-6.5) were significant independent predictors.",
            "output": [
                "Do worker recovery expectations and fear-avoidance predict work disability in a population-based workers ' compensation back pain sample?"
            ]
        },
        {
            "id": "task847-44a652d5da3a4f84ac02bd65f65af7c1",
            "input": "It is a matter of debate whether or not ordinary heading of the ball in soccer causes injury to brain tissue.', 'To analyse concentrations of the biochemical markers of brain tissue damage S-100B and neurone specific enolase (NSE) in serum of female elite soccer players in association with a competitive game.', 'Venous blood samples were obtained from 44 female soccer players before and after a competitive game for analysis. The number of headers and trauma events (falls, collisions, etc) was assessed from videotape recordings for each player.', 'Concentrations of both brain damage markers were increased after the game (S-100B, 0.18 (0.11) v 0.11 (0.05) microg/l (p = 0.000); NSE, 10.14 (1.74) v 9.05 (1.59) microg/l (p = 0.001)). There was a significant correlation between changes in S-100B concentrations and both the number of headers (r = 0.430, p = 0.004) and the number of other trauma events (r = 0.517, p < 0.001).",
            "output": [
                "Are serum concentrations of two biochemical markers of brain tissue damage S-100B and neurone specific enolase increased in elite female soccer players after a competitive game?"
            ]
        },
        {
            "id": "task847-e013cda75a084b4fa30ffe97ee413f9a",
            "input": "To determine whether there is a direct relationship between diet quality and quality of life in breast cancer survivors.', 'Subjects (n = 714) were members of the Health, Eating, Activity, and Lifestyle study, a study of breast cancer prognosis conducted in three areas of the western United States. Approximately 2 years after entry to this study, diet data were collecting using food frequency questionnaires. These data were used to classify diet quality using the Diet Quality Index. Approximately 10 months later, data on quality of life were gathered using the Medical Outcomes Study 36-Item short form health survey.', 'After controlling for age, education, race/ethnicity, body mass index, stage of disease, and time from diagnosis to quality of life measurement, women with excellent diet quality had significantly better scores than women with poor diet quality for overall mental health functioning and for 3 of 4 mental health subscale scores and 2 of 4 physical health subscale scores.",
            "output": [
                "Is diet quality directly associated with quality of life in breast cancer survivors?"
            ]
        },
        {
            "id": "task847-1acb89f9f3764c3cb97305052398ae6a",
            "input": "The purpose of this study was to describe patient satisfaction in general practice among the S\u00e1mi monolingual population, as compared with the Norwegian population.', \"The data was collected in 2002-2004 through a health survey in communities with S\u00e1mi and Norwegian population, SAMINOR. The analyses included 15,612 men and women between 36 and 79 years, with a response rate of 60.1%. The questionnaire included questions about patients' satisfaction with primary care and what language they spoke at home.\", \"The monolingual S\u00e1mi population was less satisfied with the primary health care than the Norwegian population, RR 2.4 (95% CI 2.1-2.7) and also less satisfied with the physicians' language skills, RR 5.8 (95% CI 4.8-7.0). Frequent misunderstandings between the physician and the patient based on language difficulty were also reported, RR 3.8 (95% CI 3.3-4.3). In addition, approximately one third of the S\u00e1mi did not want to have an interpreter in on the consultation.",
            "output": [
                "Is [ The monolingual S\u00e1mi population less satisfied with the primary health care ]?"
            ]
        },
        {
            "id": "task847-33189beb534b432ab96d90a16066c0ed",
            "input": "Studies examining physical activity levels have used samples primarily composed of non-Latino Whites and have focused on leisure time physical activity (LTPA). Additionally, few studies have investigated differences in physical activity between Latino men and Latina women, or the relationship between acculturation and activity.', 'To examine the subjective and objective physical activity of Latinos and gender differences in physical activity and the extent to which LTPA and non-LTPA were predictive of overall accelerometer physical activity. An additional objective was to examine the relationship between acculturation and different types of physical activity.', 'Data were obtained from 155 Latinos (n = 86 female, n = 69 male). Comparisons were made between Latino men and women.', 'Latino men participated in significantly greater occupational and overall objective and subjective physical activity than Latina women; however, women participated in greater household activity. Regression analyses demonstrated that recreational, occupational, and household activity were significant predictors of overall accelerometer physical activity for the complete sample. Among women, recreational and household activity were significant predictors; however, overall accelerometer physical activity was not significantly predicted in men. Additionally, it was demonstrated that acculturation was related to occupational activity, but not to recreational activity.",
            "output": [
                "Does gender and acculturation influence on physical activity in Latino adults?"
            ]
        },
        {
            "id": "task847-22f1b5aedd384876aa8b2a32bc90c6c0",
            "input": "In the prospectively, randomized Dutch Bone Metastasis Study on the effect of a single fraction of 8 Gy versus 24 Gy in six fractions on painful bone metastases, 28% of the patients survived for more than 1 year. Purpose of the present study was to analyze the palliative effect of radiotherapy in long-term surviving patients, and to identify prognostic factors for survival.', 'Response rates were compared in all patients surviving>52 weeks. The Cox proportional hazards model stratified by primary tumour was used for multivariate (MV) analyses of prognostic factors for survival.', 'In 320 patients surviving>52 weeks, responses were 87% after 8 Gy and 85% after 24 Gy (P=0.54). Duration of response and progression rates were similar. For all primary tumours, prognostic factors for survival were a good Karnofsky Performance Score, no visceral metastases, and non-opioid analgesics intake (all factors, MV P<0.001).",
            "output": [
                "Are patients with a favourable prognosis equally palliated with single and multiple fraction radiotherapy : results on survival in the Dutch Bone Metastasis Study?"
            ]
        },
        {
            "id": "task847-aa5697b796734d12af5c58ebadebb65e",
            "input": "A survey was undertaken to determine the extent to which acute hospitals in England, Wales and Northern Ireland were meeting the acute trauma management standards published in 2000 by The Royal College of Surgeons of England and the British Orthopaedic Association.', 'A questionnaire comprising 72 questions in 16 categories of management was distributed in July 2003 to all eligible hospitals via the link network of the British Orthopaedic Association. Data were collected over a 3-month period.', 'Of 213 eligible hospitals, 161 (76%) responded. In every category of acute care, failure to meet the standards was reported. Only 34 (21%) hospitals met all the 13 indicative standards that were considered pivotal to good trauma care, but all hospitals met at least 7 of these standards. Failures were usually in the organisation of services rather than a lack of resources, with the exception of the inadequate capacity for admission to specialist neurosurgery units. A minority of hospitals reported an inability to provide emergency airway control or insertion of chest tube. The data have not been verified and deficiencies in reporting cannot be excluded.",
            "output": [
                "Is high quality acute care for the severely injured consistently available in England , Wales and Northern Ireland : report of a survey by the Trauma Committee , The Royal College of Surgeons of England?"
            ]
        },
        {
            "id": "task847-ead089d8f81542aeada803ab4ba44a05",
            "input": "The aim of this paper is to describe the main reasons why people consult traditional healers in Mexico City.', 'The narrative of 16 traditional healers and 22 users of this type of medicine is the main source of information. This study used a qualitative approach. The field work was carried out in two stages. The first phase involved a series of observations with an ethnographic approach. During the second phase, focused interviews were held with selected informants.', 'According to participants, the main reasons for consulting traditional healers were problems with romance and love, family conflicts, economic hardships, stress,tension, nervousness and spiritual distress. These motives cannot be considered diseases in a strict sense; they were all health problems manifested as illnesses that caused suffering and only some of them could be classified as diseases within the biomedical model. People go to traditional healers not only to cure their diseases but also to obtain advice about their personal problems. As a result, traditional medicine becomes an additional option for treating human suffering, not only physical, but moral and psychological as well.",
            "output": [
                "Is [ Diseases and illnesses for which help sought from traditional healers in Mexico City ]?"
            ]
        },
        {
            "id": "task847-b3e23a88f4b94c51a6445ab3a916ba39",
            "input": "A computer-assisted microvessel analysis system was developed to evaluate correlations between the architecture of biopsy specimen microvessels and the outcome for patients with esophageal cancer treated with chemoradiotherapy.', 'Biopsy specimens from 51 patients with esophageal cancer (T(2-3), any N, M0) treated with chemoradiotherapy were immunostained with an anti-CD31 antibody and quantified using computerized image analysis. We evaluated the association of several microvessel factors with overall survival, including the ratio of total microvessel perimeter to total tumor area (TP/TA), the tumor hypoxic ratio, and the ratio of total microvessel number to total tumor area (TN/TA). Results from traditional manual microvessel density (MVD) hotspot count and computerized hotspot count were compared and the relation between hotspot MVD count and survival rate was evaluated.', 'The median follow-up time was 32 months. Both univariate and multivariate analyses revealed that computer-counted hotspot MVD and TN/TA and TP/TA ratios correlated significantly with the outcome of chemoradiotherapy. Kaplan-Meier survival curves showed that patients with high computer-counted hotspot MVDs and high TN/TA and TP/TA ratios had better overall survival rate than patients with low MVDs or ratios (P = 0.025, 0.008, and 0.031, respectively). Combining computer-counted MVD or TN/TA ratio with TP/TA ratio proved more predictive than any single factor. Two researcher-counted hotspot MVDs had no significant relation with outcome.",
            "output": [
                "Does computer-assisted analysis of biopsy specimen microvessels predict the outcome of esophageal cancers treated with chemoradiotherapy?"
            ]
        },
        {
            "id": "task847-ae3f86d227b44939a0c65c3da90e3b29",
            "input": "Neosquamous epithelium (NSE) can arise within Barrett's esophagus as a consequence of medical or surgical acid reduction therapy, as well as after endoscopic ablation. Morphologic studies have suggested that NSE can develop from adjacent squamous epithelium, submucosal gland ducts, or multipotent progenitor cell(s) that can give rise to either squamous or Barrett's epithelium, depending on the luminal environment. The cells responsible for Barrett's epithelium self-renewal are frequently mutated during neoplastic progression. If NSE arises from the same cells that self-renew the Barrett's epithelium, the two tissues should be clonally related and share genetic alterations; if NSE does not originate in the self-renewing Barrett's, NSE and Barrett's esophagus should be genetically independent.\", \"We isolated islands of NSE and the surrounding Barrett's epithelium from 20 patients by microdissection and evaluated each tissue for genetic alterations in exon 2 of CDKN2A or exons 5 to 9 of the TP53 gene. Nine patients had p16 mutations and 11 had TP53 mutations within the Barrett's epithelium.\", \"In 1 of 20 patients, a focus of NSE had a 146 bp deletion in p16 identical to that found in surrounding Barrett's epithelium. The NSE in the remaining 19 patients was wild-type for p16 or TP53.",
            "output": [
                "Does neosquamous epithelium typically arise from Barrett 's epithelium?"
            ]
        },
        {
            "id": "task847-e0cb5e9a5ce84400beb9176f9c733210",
            "input": "Transrectal ultrasound guided prostate needle biopsy (TRUS) is the standard procedure to diagnose or exclude prostate cancer. This procedure can be associated with significant discomfort, both on insertion of the ultrasound probe as well as on taking the biopsy. We evaluated a new technique for pain relief during TRUS biopsy.', 'In Group 1 (n = 60), the biopsies were taken without any analgesia. In Group 2 (n = 60), 11 ml of Instillagel (2% lignocaine) was administered rectally prior to probe insertion and 5 ml of 1% lignocaine periprostatic injection was administered before taking the biopsy. The discomfort encountered during the procedure was graded by the patient on a scale ranging from no discomfort to mild, moderate and severe pain.', 'In Group 2, there was a marked reduction in the pain experienced during the procedure. The Chi-squared test for trend showed a significant association between the rectal administration of local anaesthetic gel and reduction in pain on probe insertion (P = 0.0001). There was also a significant association between the use of periprostatic lignocaine injection and reduction in pain on taking the biopsy (P < 0.0001).",
            "output": [
                "Does the rectal administration of lignocaine gel and periprostatic lignocaine infiltration during transrectal ultrasound-guided prostate biopsy provide effective analgesia?"
            ]
        },
        {
            "id": "task847-847a4d8972ce44b491d6d83aa49a130e",
            "input": "To evaluate a possible correlation between the International Prostate Symptom Score (IPSS) and the Sexual Health Inventory for Men (SHIM) in an unselected population of men presenting to a clinic, as lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are highly prevalent in ageing men, and recent largely community-based epidemiological studies reported a close association between ED and LUTS.', 'This was a cross-sectional study in an unselected consecutive sample of 118 men aged >40 years attending a urology clinic; the reason for consulting was not ascertained. While in the waiting room the men were asked to participate in the study and on agreement were given the IPSS and the SHIM to complete.', 'The mean (range) age of the participants was 61.7 (45-82) years. Overall, 19 (16%) and 47 (40%) of the men reported having moderate or severe LUTS, respectively. Erectile problems were also common, the prevalence of moderate ED was 11% and complete ED 29%. The Pearson correlation coefficient between the IPSS and the SHIM was - 0.32 (P < 0.001).",
            "output": [
                "Are lower urinary tract symptoms and erectile dysfunction highly prevalent in ageing men?"
            ]
        },
        {
            "id": "task847-925e893a90174b2e9bd79fe560195876",
            "input": "Non-viral gene transfer efficiency is low as compared to viral vector systems. Here we describe the discovery of new drugs that are capable of enhancing non-viral gene transfer into mammalian cells using a novel two-stage screening procedure.', 'First, potential candidates are preselected from a molecular library at various concentrations by a semi-automated yeast transfection screen (YTS). The maximal transfection efficiency of every positive drug is subsequently determined in independent experiments at the optimal concentration and compared to the inhibitory effect of the drug on cell growth (IC50). In a subsequent mammalian cell transfection screen (MTS), the maximal transfection efficiency and the IC50 are determined for all preselected drugs using a human cell line and a luciferase reporter gene construct.', 'Employing our novel system we have been able to identify a new class of transfection enhancers, the tricyclic antidepressants (i.e. doxepin, maprotiline, desipramine and amoxapine). All positive drugs enhanced gene transfer in both yeast and human cell lines, but lower concentrations were sufficient for mammalian cells. With a triple combination of doxepin, amoxapine and chloroquine we obtained a transfection efficiency that exceeded that of chloroquine, one of the best-known transfection enhancers of mammalian cells, by nearly one order of magnitude.",
            "output": [
                "Does novel two-stage screening procedure lead to the identification of a new class of transfection enhancers?"
            ]
        },
        {
            "id": "task847-535bf46dc37043808c627574e838d38f",
            "input": "Canavan disease is a rare leukodystrophy with no current treatment. rAAV-ASPA has been developed for gene delivery to the central nervous system (CNS) for Canavan disease. This study represents the first use of a viral vector in an attempt to ameliorate a neurodegenerative disorder.', 'Subjects received intracranial infusions via six cranial burr holes. Adeno-associated virus, serotype 2 (AAV2), mediated intraparenchymal delivery of the human aspartoacylase cDNA at a maximum dose of 1 x 10(12) vector genomes per subject. The immune response and safety profiles were monitored in the follow-up of ten subjects.', 'Following rAAV2 administration, we found no evidence of AAV2 neutralizing antibody titers in serum for the majority of subjects tested (7/10). In a subset (3/10) of subjects, low to moderately high levels of AAV2 neutralizing antibody with respect to baseline were detected. In all subjects, there were minimal systemic signs of inflammation or immune stimulation. In subjects with catheter access to the brain lateral ventricle, cerebrospinal fluid was examined and there was a complete absence of neutralizing antibody titers with no overt signs of brain inflammation.",
            "output": [
                "Do immune responses to AAV in a phase I study for Canavan disease?"
            ]
        },
        {
            "id": "task847-3254afd206c54ef5af2dfbd0eb4942e8",
            "input": "The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci.\", 'This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis.', \"We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease.",
            "output": [
                "Does phenotype-stratified genetic linkage study demonstrate that IBD2 is an extensive ulcerative colitis locus?"
            ]
        },
        {
            "id": "task847-ad32eae01ba24c649fa5a4e00fddce38",
            "input": "This research note discusses a common misconception in speech science and speech-language pathology textbooks that rib torque (i.e., rotational stress) assists resting tidal expiration and conversational speech production.', 'The nature of this misconception is considered.",
            "output": [
                "Does rib torque assist resting tidal expiration or most conversational speech expiration?"
            ]
        },
        {
            "id": "task847-9d2907bbaa204e0da7546a26ced74387",
            "input": "Chemotactic cytokines, referred to as chemokines, play an important role in leukocyte trafficking. The circulating levels of chemokines have been shown to increase in inflammatory processes including obesity-related pathologies (e.g. atherosclerosis and diabetes). However, little is currently known about the relationship between chemokines and human obesity. In the present study, we investigated the circulating levels of selected chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), leukotactin-1, interleukin-8 (IL-8)) and the association between the chemokine levels and obesity-related parameters: body mass index (BMI), waist circumference, fasting glucose and insulin levels, lipids profile, and the level of C-reactive protein (CRP).', 'A total of 100 subjects, 50 obese (BMI>or=25 kg/m2) and 50 who were not obese (BMI<25 kg/m2) participated in the present study. The levels of chemokines and CRP were measured in a fasting state serum by sandwich enzyme-linked immunosorbent assay. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and insulin levels were measured by enzymatic analysis and immunoassay.', 'The circulating levels of MCP-1 and IL-8 in the serum were significantly (P<0.05) higher in obese subjects (BMI>30 kg/m2) compared with those of nonobese controls (BMI<25 kg/m2). The levels of CRP were positively correlated with BMI (P<0.001) or waist circumference (P<0.0001). The levels of MCP-1 and IL-8 were positively related to BMI (MCP-1, P<0.02; IL-8, P<0.01) and/or waist circumference (MCP-1, P<0.009; IL-8, P<0.03). The levels of MCP-1 were positively related to the levels of CRP (P<0.007) or interleukin-6 (IL-6) (P<0.0001), and negatively related to the levels of HDL-cholesterol (P<0.01). Homeostasis model assessment (HOMA) score was positively related to the levels of MCP-1 (P<0.02) or IL-8 (P<0.03) in obese subject.",
            "output": [
                "Are circulating levels of MCP-1 and IL-8 elevated in human obese subjects and associated with obesity-related parameters?"
            ]
        },
        {
            "id": "task847-d2a5277f62754530a0a1583bf42b2bb3",
            "input": "To investigate the impact of prophylactic hyperoxic ventilation with Fio2 0.6 on the physiologic limit of acute normovolemic anemia.', 'Prospective, controlled, randomized experimental study.', 'Experimental animal laboratory of a university hospital.', 'Fourteen anesthetized domestic pigs.', 'Animals were randomly ventilated with either Fio2 0.21 (group 0.21, n = 7) or Fio2 0.6 (group 0.6, n = 7), and acute anemia was induced by isovolemic blood-for-hydroxy-ethylstarch (HES) exchange using a 6% HES solution (130/0.4).', 'The blood-for-HES-exchange was continued until a sudden decrease of total body oxygen consumption indicated the onset of oxygen supply dependency (primary end point); the corresponding hemoglobin (Hb) concentration was defined as \"critical\" (Hb(crit)). Secondary end points were changes in myocardial function, central hemodynamics, oxygen transport, and tissue oxygenation. Compared with room air ventilation (Fio2 0.21), hyperoxic ventilation with Fio2 0.6 enabled a larger blood-for-HES-exchange (139%, 124/156) of circulating blood volume vs. 87% (68/94, p < .05), until Hb(crit) was reached (1.5 g/dL [1.4/2.1] vs. 2.4 g/dL [2.0/2.8], p < .05). At Hb 2.4 g/dL (i.e., Hb(crit) in group 0.21), animals of group 0.6 still presented with superior oxygen transport, tissue oxygenation, and hemodynamic stability. However, hemodynamic and oxygen transport variables were found deteriorated more severely at Hb 1.5 g/dL (i.e., Hb(crit) of group 0.6) compared with group 0.21 at Hb 2.4 g/dL.",
            "output": [
                "Does hyperoxic ventilation increase the tolerance of acute normovolemic anemia in anesthetized pigs?"
            ]
        },
        {
            "id": "task847-8908209bee9f4feda7bb0afbd78be99b",
            "input": "To examine the effects of combined burn and smoke inhalation injury on hypoxic pulmonary vasoconstriction, 3-nitrotyrosine formation, and respiratory function in adult sheep.', 'Prospective, placebo-controlled, randomized, single-blinded trial.', 'University research laboratory.', 'Twelve chronically instrumented ewes.', 'Following a baseline measurement, sheep were randomly allocated to either healthy controls (sham) or the injury group, subjected to a 40%, third-degree body surface area burn and 48 breaths of cotton smoke according to an established protocol (n = 6 each). Hypoxic pulmonary vasoconstriction was assessed as changes in pulmonary arterial blood flow (corrected for changes in cardiac index) in response to left lung hypoxic challenges performed at baseline and at 24 and 48 hrs postinjury.', 'Combined burn and smoke inhalation was associated with increased expression of inducible nitric oxide (NO) synthase, elevated NO2/NO3 (NOx) plasma levels (12 hrs, sham, 6.2 +/- 0.6; injury, 16 +/- 1.6 micromol.L; p < .01) and increased peroxynitrite formation, as indicated by augmented lung tissue 3-nitrotyrosine content (30 +/- 3 vs. 216 +/- 8 nM; p < .001). These biochemical changes occurred in parallel with pulmonary shunting, progressive decreases in Pao2/Fio2 ratio, and a loss of hypoxic pulmonary vasoconstriction (48 hrs, -90.5% vs. baseline; p < .001). Histopathology revealed pulmonary edema and airway obstruction as the morphologic correlates of the deterioration in gas exchange and the increases in airway pressures.",
            "output": [
                "Do combined burn and smoke inhalation injury impairs ovine hypoxic pulmonary vasoconstriction?"
            ]
        },
        {
            "id": "task847-f7ec615d5f94443e8756705934e64777",
            "input": "Passive leg raising (PLR) represents a \"self-volume challenge\" that could predict fluid response and might be useful when the respiratory variation of stroke volume cannot be used for that purpose. We hypothesized that the hemodynamic response to PLR predicts fluid responsiveness in mechanically ventilated patients.', 'Prospective study.', 'Medical intensive care unit of a university hospital.', 'We investigated 71 mechanically ventilated patients considered for volume expansion. Thirty-one patients had spontaneous breathing activity and/or arrhythmias.', 'We assessed hemodynamic status at baseline, after PLR, and after volume expansion (500 mL NaCl 0.9% infusion over 10 mins).', 'We recorded aortic blood flow using esophageal Doppler and arterial pulse pressure. We calculated the respiratory variation of pulse pressure in patients without arrhythmias. In 37 patients (responders), aortic blood flow increased by > or =15% after fluid infusion. A PLR increase of aortic blood flow > or =10% predicted fluid responsiveness with a sensitivity of 97% and a specificity of 94%. A PLR increase of pulse pressure > or =12% predicted volume responsiveness with significantly lower sensitivity (60%) and specificity (85%). In 30 patients without arrhythmias or spontaneous breathing, a respiratory variation in pulse pressure > or =12% was of similar predictive value as was PLR increases in aortic blood flow (sensitivity of 88% and specificity of 93%). In patients with spontaneous breathing activity, the specificity of respiratory variations in pulse pressure was poor (46%).",
            "output": [
                "Does passive leg raising predict fluid responsiveness in the critically ill?"
            ]
        },
        {
            "id": "task847-f0a72f55aa4849d386aa42f722bb4518",
            "input": "Pathologic change in Alzheimer disease (AD) begins some years before symptoms. MRS has the potential to detect metabolic abnormalities reflecting this early pathologic change. Presenilin 1 (PS1) and amyloid precursor protein (APP) mutation carriers have a nearly 100% risk of developing AD and may be studied prior to symptom onset.', 'Short echo time proton MR spectra were acquired from a midline posterior cingulate voxel in presymptomatic carriers of PS1 or APP mutations (\"presymptomatic mutation carriers\" [PMCs]; n = 7) and age- and sex-matched control subjects (n = 6). Ratios of N-acetyl aspartate (NAA), myo-inositol (MI), and choline-containing compounds (Cho) to creatine (Cr) were measured and NAA/MI calculated. Regression analyses and t tests were performed after log transformation.', 'PMC and control subjects were matched for age and sex. PMC subjects were 1.7 to 21.6 years (mean 9.8 years) before expected symptom onset, predicted from family-specific mean age at onset. Age did not significantly affect metabolite ratios. Geometric mean ratios in control subjects were as follows: NAA/Cr = 1.75, MI/Cr = 0.59, and NAA/MI = 2.95. NAA/Cr and NAA/MI were significantly reduced in PMC relative to controls (NAA/Cr mean decrease 10% [95% CI 2 to 18%]; NAA/MI mean decrease 25% [95% CI 3 to 44%]). MI/Cr was increased in PMC, but the differences did not achieve significance (19% increase [95% CI 1% decrease to 41% increase]; p = 0.07)). In PMCs, reduction in NAA/MI (p = 0.001) and MI/Cr (p = 0.002) were related to proximity of expected age at onset.",
            "output": [
                "Does mRS show abnormalities before symptoms in familial Alzheimer disease?"
            ]
        },
        {
            "id": "task847-9e8d9b0391f54246b4f803b545db3e3a",
            "input": "Therapeutic intervention during the early stages of an intracerebral hemorrhage (ICH) might have value in improving clinical outcomes. During the 73-site International Recombinant Activated Factor VII Intracerebral Hemorrhage Trial, CT techniques were used to monitor the change in hematoma volume in response to treatment. The use of CT imaging technology served 3 functions: to provide accurate measurements of the change in hematoma volume, intraventricular volume (IVH), and edema volume; to evaluate the use of CT scans as a predictor of patient outcomes; and to demonstrate that hematoma volume can serve as a surrogate marker for ICH clinical progression.', 'The multicenter clinical trial received institutional review board approval and obtained informed consent from the patient or a legally acceptable representative (waived in a few cases of incapacity, according to local and national regulations). CT scans were used to quantify volumes of hemorrhage and to monitor evolution over a 72-hour period in patients with ICH treated with placebo or 40, 80, or 160 microg/kg of recombinant activated factor VII (rFVIIa). CT image data were transmitted digitally to an imaging laboratory and analyzed by 2 readers masked to patient and treatment data, by using Analyze software, a fully integrated toolkit for interactive display, processing, and measurement of biomedical image data. The use of this software enabled the evaluation of intraclass variability of CT scan interpretations.', 'Interpretations of ICH and IVH volumes of CT scans in patients treated in this study showed minimal intraclass variability. Variability was greatest for interpretations of edema volume.",
            "output": [
                "Do radiologic estimation of hematoma volume in intracerebral hemorrhage trial by CT scan?"
            ]
        },
        {
            "id": "task847-adb17c4ff8974263a06f4fe52efda5fb",
            "input": "Psoriasis appears to have increased cardiovascular morbidity. The underlying pathogenetic mechanisms remain unclear. Multiple factors, including systemic inflammation, oxidative stress, aberrant lipid profile, and concomitant established risk factors, have been discussed. However, previous studies consist of heterogeneous patient materials, including persons with highly varying disease duration and treatment.', 'Two-hundred patients were investigated at the onset of psoriasis, comparing plasma concentrations of lipids, lipoproteins, and apolipoproteins with those of matched controls (N = 285).', 'Psoriasis patients manifest significant lipid abnormalities. Specifically, patients had significantly higher cholesterol concentrations in the very-low-density lipoprotein and high-density-lipoprotein fractions. Adjustment for established environmental risk factors did not affect the results.",
            "output": [
                "Is psoriasis associated with lipid abnormalities at the onset of skin disease?"
            ]
        },
        {
            "id": "task847-551c504379a04419849d6559771e0ca8",
            "input": "We investigated the effects of pulsed ultrasound on swelling, muscle soreness perception, relaxed-elbow extension angle, and muscular strength.', 'Eight sets of concentric and eccentric actions induced delayed-onset muscle soreness of the elbow flexors. Group 1 received 20% pulsed ultrasound treatments (1-MHz, 7 minutes, 1.5 W/ cm(2) temporal peak intensity) twice a day immediately after postexercise assessments and at 3, 24, 27, 48, 51, 72, and 75 hours postexercise. Group 2 received sham treatments immediately after postexercise assessments and at 3,27, 51, and 75 hours postexercise and true treatments of pulsed ultrasound at 24, 48, and 72 hours postexercise. Group 3 received sham treatments of no ultrasonic output immediately after postexercise assessments and at 3, 24, 27, 48, 51, 72, and 75 hours postexercise.', 'Thirty-six college-age females.', 'We recorded upper-arm circumference, perceived soreness, relaxed-elbow extension angle, and elbow-flexion strength before (pretest), immediately postexercise, and at 24, 48, 72, and 96 hours postexercise.', 'We noted differences over time but no treatment effect between groups or interactions between time and group for upper-arm circumference, perceived soreness, relaxed-elbow extension angle, or elbow-flexion strength.",
            "output": [
                "Does pulsed ultrasound fail to diminish delayed-onset muscle soreness symptoms?"
            ]
        },
        {
            "id": "task847-f0c34a407bb845b3a5d92807c8e1c163",
            "input": "Contrast therapy has a long history of use in sports medicine. Edema and ecchymosis reduction, vasodilation and vasoconstriction of blood vessels, blood flow changes, and influences on the inflammatory response are physiologic effects attributed to the ability of this modality to evoke tissue temperature fluctuations. Our purpose was to measure the change in human gastrocnemius intramuscular tissue temperature during a typical contrast therapy treatment.', 'A randomized-group design was used to examine differences between 2 groups of subjects following a 31-minute warm whirlpool (control) and a 31-minute contrast therapy (experimental) treatment. A hydrotherapy room in a small- college sports medicine facility served as the test environment.', 'Twenty (7 females and 13 males) healthy college students (age = 20.9 +/- 1.2 years; ht = 178.5 +/- 11.1 cm; wt = 79.2 +/- 21.7 kg) volunteered to participate in this study. Subjects were randomly assigned to either a control or a treatment group.', 'Intramuscular tissue temperatures in the gastrocnemius were recorded every 30 seconds.', 'There was a significant difference in mean overall temperature change between the experimental group (0.85 degrees C +/- 0.60 degrees C) and the control group (2.10 degrees C +/- 1.50 degrees C). In addition, there were significant differences between the 2 groups at 10, 15, 16, 20, 21, 25, 26, 30, and 31 minutes. At each recording point, the control group temperature change was significantly higher than that of the experimental group. There was no difference in absolute temperatures at the 11-minute recording point between the groups.",
            "output": [
                "Does contrast therapy cause fluctuations in human gastrocnemius intramuscular temperature?"
            ]
        },
        {
            "id": "task847-e76e640fa24748c1aa0e806ecc823850",
            "input": "We compare the effects of postinjury administration of allopregnanolone, a metabolite of progesterone, to progesterone in an animal model of transient middle cerebral artery occlusion.', 'Focal cerebral ischemia was induced in age-matched, adult, male, Sprague-Dawley rats by using an intraluminal filament and suture method to occlude the right middle cerebral artery. After 120 minutes of middle cerebral artery occlusion, the occluding filament was withdrawn to allow reperfusion. Laser-Doppler flowmetry was used to monitor cerebral blood flow for the entire 2-hour period of occlusion and for 5 minutes after reperfusion. Animals subjected to middle cerebral artery occlusion received injections of allopregnanolone (8 mg/kg, n=6), progesterone (8 mg/kg, n=6) and vehicle (2-hydroxypropyl-beta-cyclodextrin, n=7) at 2 hours (intraperitoneally 5 minutes before reperfusion) and 6 hours (subcutaneously) postocclusion. Brains were removed at 72 hours post-middle cerebral artery occlusion, sectioned into coronal slices, and stained with 2,3,5-triphenyltetrazolium chloride (TTC). In a blinded analysis, infarct volume was calculated by using computer-aided morphometry to measure brain areas not stained with TTC.', 'After progesterone or allopregnanolone treatment, stained sections revealed a significant reduction in cortical, caudate-putamen, and hemispheric infarct volumes (percentage of contralateral structure) compared with vehicle-injected controls. Cortical infarction (percentage of contralateral cortex) was 37.47%+/-10.57% (vehicle), 25.49%+/-7.38% (progesterone; P<.05 from vehicle), and 11.40%+/-7.09% (allopregnanolone; P<.05 from vehicle; P<.05 from progesterone). Caudate-putamen infarction (percentage of contralateral caudate-putamen) was 78.02%+/-22.81% (vehicle), 48.41%+/-22.44% (progesterone; P<.05 from vehicle), and 50.44%+/-10.90% (allopregnanolone; P<.05 from vehicle). Total hemispheric infarction (percentage of contralateral hemisphere) was 24.37%+/-6.69% (vehicle), 15.95%+/-3.59% (progesterone; P<.05 from vehicle), and 11.54%+/-3.71% (allopregnanolone; P<.05 from vehicle). No significant differences in cerebral blood flow between groups and time points during ischemia and early reperfusion were observed, suggesting that the relative ischemic insult was equivalent among all groups.",
            "output": [
                "Is allopregnanolone , a progesterone metabolite , more effective than progesterone in reducing cortical infarct volume after transient middle cerebral artery occlusion?"
            ]
        },
        {
            "id": "task847-e958615a19d14ac1ab728e64cc537bb6",
            "input": "Uncontrolled trials suggest biofeedback is an effective treatment for pelvic floor dyssynergia (PFD), a type of constipation defined by paradoxical contraction, or inability to relax, pelvic floor muscles during defecation. The aim was to compare biofeedback to laxatives plus education.', 'Patients with chronic, severe PFD were first treated with 20 g/day fiber plus enemas or suppositories up to twice weekly. Nonresponders were randomized to either 5 weekly biofeedback sessions (n = 54) or polyethylene glycol 14.6-29.2 g/day plus 5 weekly counseling sessions in preventing constipation (n = 55). Satisfaction with treatment, symptoms of constipation, and pelvic floor physiology were assessed 6 and 12 months later. The biofeedback group was also assessed at 24 months. Laxative-treated patients were instructed to increase the dose of polyethylene glycol from 14.6 to 29.2 g/day after 6 months.', \"At 6 months, major improvement was reported by 43 of 54 (80%) biofeedback patients vs 12 of 55 (22%) laxative-treated patients (P < .001). Biofeedback's benefits were sustained at 12 and 24 months. Biofeedback also produced greater reductions in straining, sensations of incomplete evacuation and anorectal blockage, use of enemas and suppositories, and abdominal pain (all P < .01). Stool frequency increased in both groups. All biofeedback-treated patients reporting major improvement were able to relax the pelvic floor and defecate a 50-mL balloon at 6 and 12 months.",
            "output": [
                "Is biofeedback superior to laxatives for normal transit constipation due to pelvic floor dyssynergia?"
            ]
        },
        {
            "id": "task847-b69ea81748e94d95ab108c4023492578",
            "input": "Progesterone (P) and its 5alpha-reduced metabolite, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP), facilitate sexual behavior of rodents via agonist-like actions at intracellular progestin receptors (PRs) and membrane GABA(A)/benzodiazepine receptor complexes (GBRs), respectively.', 'Given that ovarian secretion of progestins declines with aging, whether or not senescent mice are responsive to progestins was of interest.', 'Homozygous PR knockout (PRKO) or wild-type mice that were between 10-12 (mid-aged) or 20-24 (aged) months of age were administered P or 3alpha,5alpha-THP, and the effect on lordosis were examined. Effects of a progestin-priming regimen that enhances PR-mediated (experiment 1) or more rapid, PR-independent effects of progestins (experiments 2 and 3) on sexual behavior were examined. Levels of P, 3alpha,5alpha-THP, and muscimol binding were examined in tissues from aged mice (experiment 4).', 'Wild-type, but not PRKO, mice were responsive when primed with 17beta-estradiol (E(2); 0.5 microg) and administered P (500 microg, subcutaneously). Mid-aged wild-type mice demonstrated greater increases in lordosis 6 h later compared to their pre-P, baseline test than did aged wild-type mice (experiment 1). Lordosis of younger and older wild-type, but not PRKO, mice was significantly increased within 5 min of intravenous (IV) administration of P (100 ng), compared with E(2)-priming alone (experiment 2). However, wild-type and PRKO mice demonstrated significant increases in lordosis 5 min after IV administration of 3alpha,5alpha-THP, an effect which was more pronounced in mid-aged than in aged animals (100 ng-experiment 3). In tissues from aged wild-type and PRKO mice, levels of P, 3alpha,5alpha-THP, and muscimol binding were increased by P administration (experiment 4). PR binding was lower in the cortex of PRKO than that of wild-type mice.",
            "output": [
                "Do mid-aged and aged wild-type and progestin receptor knockout ( PRKO ) mice demonstrate rapid progesterone and 3alpha,5alpha-THP-facilitated lordosis?"
            ]
        },
        {
            "id": "task847-5720e50f94434e908ec6836959dd79e4",
            "input": "Oncogenic conversion of BRAF occurs in approximately 44% of papillary thyroid carcinomas and 24% of anaplastic thyroid carcinomas. In papillary thyroid carcinomas, this mutation is associated with an unfavorable clinicopathologic outcome. Our aim was to exploit BRAF as a potential therapeutic target for thyroid carcinoma.', \"We used RNA interference to evaluate the effect of BRAF knockdown in the human anaplastic thyroid carcinoma cell lines FRO and ARO carrying the BRAF V600E (V600EBRAF) mutation. We also exploited the effect of BAY 43-9006 [N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoyl pyridin-4-yl)oxyphenyl)urea], a multikinase inhibitor able to inhibit RAF family kinases in a panel of six (V600E)BRAF-positive thyroid carcinoma cell lines and in nude mice bearing ARO cell xenografts. Statistical tests were two sided.\", 'Knockdown of BRAF by small inhibitory duplex RNA, but not control small inhibitory duplex RNA, inhibited the mitogen-activated protein kinase signaling cascade and the growth of ARO and FRO cells (P < 0.0001). These effects were mimicked by thyroid carcinoma cell treatment with BAY 43-9006 (IC50 = 0.5-1 micromol/L; P < 0.0001), whereas the compound had negligible effects in normal thyrocytes. ARO cell tumor xenografts were significantly (P < 0.0001) smaller in nude mice treated with BAY 43-9006 than in control mice. This inhibition was associated with suppression of phospho-mitogen-activated protein kinase levels.",
            "output": [
                "Is bRAF a therapeutic target in aggressive thyroid carcinoma?"
            ]
        },
        {
            "id": "task847-2af328b0448844ab81e6a753975348d3",
            "input": "Stomatin-like protein 2 (SLP-2) is a novel and unusual stomatin homologue of unknown functions. It has been implicated in interaction with erythrocyte cytoskeleton and presumably other integral membrane proteins, but not directly with the membrane bilayer. We show here the involvement of SLP-2 in human esophageal squamous cell carcinoma (ESCC), lung cancer, laryngeal cancer, and endometrial adenocarcinoma and the effects of SLP-2 on ESCC cells.', 'Previous work of cDNA microarray in our laboratory revealed that SLP-2 was significantly up-regulated in ESCC. The expression of SLP-2 was further evaluated in human ESCC, lung cancer, laryngeal cancer, and endometrial adenocarcinoma by semiquantitative reverse transcription-PCR, Western blot, and immunohistochemistry. Mutation detection of SLP-2 exons was done by PCR and automated sequencing. Antisense SLP-2 eukaryotic expression plasmids were constructed and transfected into human ESCC cell line KYSE450. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, clonogenecity assay, flow cytometry assay, nude mice tumorigenetic assay, and cell attachment assay were done to investigate the roles of SLP-2 gene.', 'All tumor types we tested showed overexpression of SLP-2 compared with their normal counterparts (P < or = 0.05). Moreover, immunohistochemistry analysis of mild dysplasia, severe dysplasia, and ESCC showed that overexpression of SLP-2 occurred in premalignant lesions. Mutation analysis indicated that no mutation was found in SLP-2 exons. KYSE450 cells transfected with antisense SLP-2 showed decreased cell growth, proliferation, tumorigenecity, and cell adhesion.",
            "output": [
                "Is stomatin-like protein 2 overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-555848ab1b0d4bf79b34789a98512c0c",
            "input": "Oxidative stress occurs in chronic renal failure patients undergoing hemodialysis (HD). The objective of our study was to measure oxidation products of cholesterols, so-called oxysterols, in the serum of HD patients in comparison to healthy control persons.', 'In 42 HD patients, plasma oxysterols were measured before and after HD. The values were compared with those in 40 healthy controls. The following cholesterol derivatives were analyzed: dienes, 7beta-OH, beta-epoxy, alpha-epoxy, 20alpha-OH, alpha-triol, and 7-keto cholesterol.', 'In HD patients, serum levels of oxysterols are increased in comparison to controls. The highest values were measured for beta-epoxy cholesterol and for 20alpha-OH cholesterol. During HD oxysterol concentrations increased, obviously by water removal and concentration of nondialyzable compounds.",
            "output": [
                "Are oxysterols increased in plasma of end-stage renal disease patients?"
            ]
        },
        {
            "id": "task847-13e526d59c1f484bb14ed45d329adad9",
            "input": "Oxidative stress often occurs in chronic hemodialysis (HD) patients. The objective of our study was to investigate the interrelationship between oxidative stress and the degree of renal anemia.', 'In 107 consecutive HD patients, serum concentrations of two major aldehydic lipid peroxidation (LPO) products, 4-hydroxynonenal (HNE) and malondialdehyde (MDA), and of protein carbonyls were analyzed as parameters of oxidative stress and related to the degree of renal anemia. Additionally, in 76 patients treated with epoetin long-term changes in the serum levels of aldehydic LPO products were observed.', 'In HD patients, serum levels of HNE, MDA, and protein carbonyls are increased in comparison to controls. The lower the hemoglobin, i.e. the stronger the degree of renal anemia, the higher the serum concentrations of HNE, MDA, and protein carbonyls. The HNE and MDA levels decreased during HD. Long-term studies on the correction of renal anemia by epoetin demonstrated a mitigation of oxidative stress during this therapy. During periods of 1 and 2 years, it was observed that the serum levels of HNE and MDA could be reduced.",
            "output": [
                "Is oxidative stress in renal anemia of hemodialysis patients mitigated by epoetin treatment?"
            ]
        },
        {
            "id": "task847-750126786a324734801ee6ca6926c40e",
            "input": "To compare the frequency of Pap test results in a prospective series of direct to vial ThinPrep tests to a cohort of conventionally prepared tests. To follow-up all test results for a minimum of 2 years and assess performance based on this outcome.', 'All women presenting for either routine screening or colposcopic examination in 2001 were enrolled in the ThinPrep cohort. A similar, population of conventionally prepared tests was extracted from the year 2000 laboratory data. Information on all concurrent and follow-up cervical specimens over the ensuing 2 years was retrieved.', 'The ThinPrep cohort comprised 2288 Pap tests and the conventional, 2211. The frequency of normal [within normal limits (WNL) and benign cellular changes (BCC)] results in the ThinPrep cohort was 6% lower and the frequency of abnormal [> or =atypical squamous cells of undetermined significance (ASCUS)] results was 6.8% higher. Respective ThinPrep and conventional cohort results were 1156 (51%) and 1291 (58%) WNL, 625 (27%) and 561 (25%) BCC, 101 (4%) and 65 (3%) ASCUS, 21 (1%) and 2 (0.1%) atypical glandular cells of undetermined significance, 301 (13%) and 224 (10%) low-grade squamous intraepithelial lesion (LSIL), and 74 (3%) and 40 (2%) high-grade SIL (HSIL) (P < 0.0001). Follow-up was available for nearly 80% of each cohort. LSIL or higher was confirmed in 57.5% (n = 266) of the abnormal ThinPrep and 60.9% (n = 190) of the abnormal conventional tests. The ThinPrep yield of confirmed tests however was almost 50% higher than the conventional test.",
            "output": [
                "Does comparative study of the ThinPrep Pap test and conventional cytology result in a Canadian cohort?"
            ]
        },
        {
            "id": "task847-97d0fd92b98e4b3eb18d061aa8725c0b",
            "input": "To study the role of beta1 integrins in left ventricular (LV) remodelling after myocardial infarction (MI).', 'LV structural and functional alterations were determined in wild-type (WT) and beta1 integrin heterozygous knockout (hKO) mice one month after MI. MI increased beta1 integrin expression in both groups; however, the increase was lower in hKO. Infarct size was similar in WT and hKO mice, whereas lung wet weight to dry weight ratio was increased in the hKO-MI mice (5.17 (SE 0.13) v 4.60 (0.15) in WT-MI, p < 0.01). LV end systolic and end diastolic diameters were significantly higher and percentage fractional shortening was significantly lower in hKO-MI. The ratio of peak velocity of early LV filling (E wave) to that of the late LV filling (A wave) and the isovolumic relaxation time (IVRT) were increased in both MI groups but the increase in IVRT was significantly higher in hKO-MI group than in WT-MI mice. Langendorff perfusion analysis indicated reduced peak LV developed pressure and increased LV end diastolic pressure in both MI groups. The reduction in peak LV developed pressure (36.7 (2.2) v 53.4 (1.9) mm Hg, p < 0.05) and increase in LV end diastolic pressure was higher in hKO-MI than in WT-MI. Increase in fibrosis was not different between the two MI groups. The increase in myocyte circumference was higher in the hKO-MI group (p < 0.001 v WT-MI). The number of apoptotic myocytes was significantly higher in hKO-MI than in WT-MI mice (p < 0.005) three days after MI. The number of necrotic myocytes was not different between the two MI groups.",
            "output": [
                "Does deficiency of beta1 integrins result in increased myocardial dysfunction after myocardial infarction?"
            ]
        },
        {
            "id": "task847-63bb308737c74fe2b0baf2d45126922e",
            "input": "Inflammation plays a pathogenic role in the development of heart failure (HF). The aim of this study was to examine the effect of treatment with the immunomodulating drug thalidomide in a rat model for post-myocardial infarction (MI) HF.', 'Rats were subjected to MI by left coronary artery ligation or sham-operated. Seven days after surgical intervention rats were randomised to treatment with thalidomide or vehicle for 8 weeks.', 'Our main findings were: (i) thalidomide treatment did not affect cardiac function or the hypertrophic response, as determined by haemodynamic measurements and heart chamber weights, respectively. (ii) HF rats treated with thalidomide had a minor reduction in septum and relative wall thickness (p<0.05), indicating an anti-remodelling effect. (iii) Thalidomide appeared to have immunostimulatory effects on the myocardium as evident by increased MIP-1alpha gene expression (p<0.05). (iv) Treating HF rats with thalidomide reduced myocardial collagen content, as assessed by markedly decreased levels of hydroxyproline ( approximately 40% reduction; p<0.05), accompanied by lower TGF-beta(1) gene expression (p<0.05).",
            "output": [
                "Does thalidomide attenuate the development of fibrosis during post-infarction myocardial remodelling in rats?"
            ]
        },
        {
            "id": "task847-3adae588279c429eab27395eba06cc5f",
            "input": "Cyclosporine is a molecule used in ophthalmology for the prevention of corneal graft rejection. The systemic use of this product can lead to serious adverse side effects that can be avoided using the topical formulation of cyclosporine. However, cyclosporine application can induce ocular irritation.', 'The aim of this study is to evaluate the cytotoxicity of four formulations of 2% cyclosporine eye drops: Sandimmum intravenous solution diluted with NaCl 0.9%, Sandimmun oral solution diluted in castor oil or corn oil after ethanol evaporation, and Sandimmun oral solution diluted in castor oil without previous ethanol evaporation. Two tests--the Draize test and the evaluation of cytotoxicity of adherent alive cells with cold light cytofluorimetry on microplates--were used in this study.', 'These tests demonstrated that the aqueous solution shows more toxicity than the other formulations, and the type of oil and ethanol concentration influence cell viability.",
            "output": [
                "Does [ Cytotoxicity evaluation of different eyes drop with cyclosporine oral solution ( Sandimmun ) ]?"
            ]
        },
        {
            "id": "task847-dd126be75e0e48308b8ffafb7a73d093",
            "input": "To examine whether hypercapnia in very low birth weight (VLBW) infants during the first 3 days of life is associated with severe intraventricular hemorrhage (IVH).', 'Retrospective cohort study of inborn VLBW infants between January 1999 and May 2004 with arterial access during the first 3 days of life. A multiple logistic regression analysis was used where IVH was dichotomized ((grades 0/1/2) = non-severe; (grades 3/4) = severe). Measures of hypercapnia were entered into the model to ascertain their association with severe IVH.', 'In total, 574 VLBW infants met entry criteria. Worst IVH grade was 0 in 400; 1: 54; 2: 42; 3: 47; and 4: 31 infants. The logistic regression model consisted of the following predictors of severe IVH: gestational age, gender, 1 min Apgar score (dichotomized into two groups: >3 vs < or =3), multifetal gestation, vasopressor use, and maximum PaCO(2).",
            "output": [
                "Is hypercapnia during the first 3 days of life associated with severe intraventricular hemorrhage in very low birth weight infants?"
            ]
        },
        {
            "id": "task847-5d2767a7409640e984c5bd41b4954d94",
            "input": "The 1858C/T SNP of the PTPN22 gene has been associated with many autoimmune diseases, suggesting the existence of an inflammatory process common to all of them. We studied the association of that polymorphism with immunoglobulin A deficiency (IgAD) following a double approach: a case-control and a TDT study.', \"A total of 259 IgAD patients and 455 unrelated matched controls, and 128 families were used for each approach. Comparisons were performed using Chi-Square tests or Fisher's exact test when necessary.\", 'No association between the PTPN22 1858C/T SNP and IgA deficiency was found in any case (allelic frequencies 8% vs. 6% in patients and controls, respectively, OR= 1.14 (0.72-1.79), p= 0.56; TDT p = 0.08).",
            "output": [
                "Is a functional PTPN22 polymorphism associated with several autoimmune diseases associated with IgA deficiency in the Spanish population?"
            ]
        },
        {
            "id": "task847-7ae0d24591df4602ab89540d78fb8fc7",
            "input": "A number of gene therapy applications would benefit from vectors capable of expressing multiple genes. In this study we explored the feasibility and efficiency of expressing two or three transgenes in HIV-1 based lentiviral vector. Bicistronic and tricistronic self-inactivating lentiviral vectors were constructed employing the internal ribosomal entry site (IRES) sequence of encephalomyocarditis virus (EMCV) and/or foot-and-mouth disease virus (FMDV) cleavage factor 2A. We employed enhanced green fluorescent protein (eGFP), O6-methylguanine-DNA-methyltransferase (MGMT), and homeobox transcription factor HOXB4 as model genes and their expression was detected by appropriate methods including fluorescence microscopy, flow cytometry, immunocytochemistry, biochemical assay, and western blotting.', 'All the multigene vectors produced high titer virus and were able to simultaneously express two or three transgenes in transduced cells. However, the level of expression of individual transgenes varied depending on: the transgene itself; its position within the construct; the total number of transgenes expressed; the strategy used for multigene expression and the average copy number of pro-viral insertions. Notably, at limiting MOI, the expression of eGFP in a bicistronic vector based on 2A was approximately 4 times greater than that of an IRES based vector.",
            "output": [
                "Do multicistronic lentiviral vectors containing the FMDV 2A cleavage factor demonstrate robust expression of encoded genes at limiting MOI?"
            ]
        },
        {
            "id": "task847-cc21b9f7aaa94aa1a5964ec007f42b56",
            "input": "Ischemia/reperfusion injury is an inherent consequence of solid organ transplantation that increases tissue inflammation and negatively impacts organ transplant function and survival. This study investigated the expression levels of chemokine and chemokine receptor genes in living versus cadaver donor renal allografts before and after reperfusion.', 'This study involved 39 renal transplant patients (19 cadaveric and 20 living donor). The ischemia biopsy was taken just before graft declamping and the reperfusion biopsy 30 min after declamping. Whole-cell RNA was isolated and chemokine (IL-8, CCL2/MCP-1, CXCL10/IP-10 and CCL5/RANTES) and chemokine receptor (CCR2 and CCR5) expression was tested by quantitative PCR.', 'Just prior to declamping, ischemic cadaveric donor grafts had higher expression of CXCL10/IP-10 but not IL-8 or CCL2/MCP-1 than living donor grafts. IL-8 expression increased 50% from ischemia to reperfusion in living donor grafts but increased more than 13-fold during reperfusion of cadaver donor grafts. Increased total ischemia time induced greater IL-8 expression during reperfusion. MCP-1 expression also increased during reperfusion of living and cadaver donor grafts but differences were not observed between the two groups of grafts. RANTES, CCR2, and CCR5 expression did not change in ischemic vs. reperfusion biopsies.",
            "output": [
                "Is expression of IL-8 during reperfusion of renal allografts dependent on ischemic time?"
            ]
        },
        {
            "id": "task847-321cc2658a574693aa3ab22289ee890f",
            "input": "We previously established hepatitis C virus (HCV) replicon-harboring cell lines possessing two interferon (IFN)-resistant phenotypes: a partially resistant phenotype (alphaR series) and a severely resistant phenotype (betaR series). We recently found that the severe IFN resistance of the betaR-series cells is caused by the functional disruption of type I IFN receptors. Here, we aimed to clarify the mechanism(s) underlying the partial IFN resistance of the alphaR-series cells.', 'alphaR-series cells were pre-treated with 5-azacytidine to evaluate the effects of DNA demethylation on IFN resistance. cDNA microarray analysis was carried out in order to compare 1alphaR cells, which belong to the alphaR series, treated with both 5-azacytidine and IFN-alpha with cells treated with 5-azacytidine or IFN-alpha alone.', 'We found that the IFN-resistant phenotype of alphaR-series cells was impaired by treatment with 5-azacytidine. cDNA microarray analysis identified seven IFN-stimulated genes, which were up-regulated by 5-azacytidine treatment. We demonstrated here that the ectopic expression of each of these seven genes in 1alphaR cells frequently weakened the IFN resistance of these cells.",
            "output": [
                "Is epigenetic silencing of interferon-inducible genes implicated in interferon resistance of hepatitis C virus replicon-harboring cells?"
            ]
        },
        {
            "id": "task847-64b51d53e21e4ab18f230a019f52b636",
            "input": "Cirrhotic livers have a deficient vasodilator response to nitric oxide (NO). The vasodilator effect of NO is normally limited by the degradation of its second messenger cyclic guanosine 3', 5' monophosphate by phosphodiesterases. We investigated (1) the phosphodiesterase-5 (PDE-5) expression in normal and cirrhotic rat livers, (2) the location of the deficient response to NO in cirrhotic livers, and (3) the effect of the PDE-5 inhibitor Sildenafil citrate on this deficient response.\", 'Normal and ascitic cirrhotic rats were subjected to liver perfusion with continuous measurement of both perfusion and sinusoidal (wedge hepatic) pressures. After incubation with N-monomethyl-l-arginine and pre-constriction with Methoxamine, concentration-response curves to the spontaneous NO donor S-nitroso-N-acetylpenicillamine were obtained in the absence or presence of Sildenafil (10(-8)M).', 'PDE-5 expression (Western blot) in cirrhotic livers was higher than in normal livers (P=0.042). Compared to normal livers, cirrhotic livers showed a decreased response to S-nitroso-N-acetylpenicillamine in the pre-sinusoidal area (P=0.003) but not in the sinusoidal/post-sinusoidal area (P=0.433). In the presence of Sildenafil, normal and cirrhotic livers showed similar pre-sinusoidal (P=0.419) and sinusoidal/post-sinusoidal (P=0.875) responses to S-nitroso-N-acetylpenicillamine.",
            "output": [
                "Is increased phosphodiesterase-5 expression involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers?"
            ]
        },
        {
            "id": "task847-9349e418576a46589c087b3ec7595fb0",
            "input": "Genetic variants in DLG5, which encodes a scaffolding protein on chromosome 10q23, and tumor necrosis factor (TNF)-alpha, encoding a proinflammatory cytokine on chromosome 6p, have recently been reported to be associated with inflammatory bowel disease (IBD). We studied these variants to seek evidence of association with IBD in a large independent dataset.', \"We genotyped 1104 unrelated white IBD subjects-496 with Crohn's disease, 512 with ulcerative colitis, and 96 with indeterminate colitis from the Cambridge/Eastern (UK) panel-and 760 healthy control subjects for DLG5_113G/A, DLG5_4136C/A, TNF-857C/T, and TNF-1031T/C polymorphisms. Known Crohn's disease-predisposing variants in CARD15/NOD2 were also genotyped to permit analysis for reported epistatic interactions.\", \": TNF-857 was shown to be associated with IBD overall (P = 0.0079). A formal interaction test showed that TNF-857 is associated equally with ulcerative colitis and Crohn's disease. Neither of the DLG5 alleles, however, was associated with IBD (P = 0.32 and 0.35). Subgroup analysis also failed to show evidence of association between either DLG5 allele or genotype frequencies and ulcerative colitis or Crohn's disease. Stratification of TNF-alpha and DLG5 cases by CARD15 genotype made no significant difference in the strength of associations.",
            "output": [
                "Are genetic variants in TNF-alpha but not DLG5 associated with inflammatory bowel disease in a large United Kingdom cohort?"
            ]
        },
        {
            "id": "task847-3762d5948b9044cea672a73eb232c442",
            "input": "Schizophrenia and autism are clinically distinct yet both disorders are characterised by theory of mind (ToM) deficits. Autistic individuals fail to appreciate false beliefs, yet understand the causal connections between behavioural events and simple emotions. Findings of this type have promoted the view that ToM deficits in autism reflect a domain-specific difficulty with appreciating the representational nature of epistemic mental states (i.e., beliefs and intentions and not emotions). This study examines whether the same holds true for schizophrenia.', \"A picture-sequencing task assessed capacity to infer false beliefs in patients with schizophrenia and healthy controls. To assess emotion attribution, participants were shown cartoon strips of events likely to elicit strong emotional reactions in story characters. Characters' faces were blanked out. Participants were instructed to think about how the characters would be feeling in order to match up the cards depicting facial affect appropriately. Participants later named emotions depicted in facial affect cards.\", 'Patients were as capable as controls of identifying cartoon facial expressions, yet had greater difficulties with: (a) attributing emotions based on circumstances; and (b) inferring false beliefs.",
            "output": [
                "Is empathetic perspective-taking impaired in schizophrenia : evidence from a study of emotion attribution and theory of mind?"
            ]
        },
        {
            "id": "task847-847d9c76567f4eb28e2da4c06f0ede06",
            "input": "Surgery has been the gold standard in the treatment of adult pyloric stenosis (APS). The introduction of proton pump inhibitors (PPIs) in 1989 revolutionised the treatment of peptic ulcer disease and its complications.', 'We carried out a prospective study to evaluate the effectiveness of PPIs as an alternative to surgery for treatment of APS. Six consecutive patients admitted with a diagnosis of adult peptic pyloric stenosis between November 1999 and August 2002 were studied. The diagnosis was confirmed with endoscopy. All patients were commenced on a twice-daily dose of intravenous PPI. This was changed to oral treatment after 2 days. Main outcome measures evaluated were resolution of symptoms on PPIs and failure of medical therapy.', 'There were five females and one male. Median age at diagnosis was 72 years (range, 30-90 years). Median duration of symptoms was 2 weeks (range, 1-5 weeks). Of the patients, five had a history of peptic ulcer disease. Complete resolution was achieved in 5 patients (83%). Median duration for resolution of symptoms was 9 days (range, 5-14 days). All patients were changed to oral PPIs after 2 days. One patient did not respond to oral therapy and required surgical intervention (pyloroplasty). Median follow-up was 26 months (range, 6-48 months). There was no recurrence of symptoms. All patients were discharged on low-dose PPI.",
            "output": [
                "Is proton pump inhibition a feasible primary alternative to surgery and balloon dilatation in adult peptic pyloric stenosis ( APS ) : report of six consecutive cases?"
            ]
        },
        {
            "id": "task847-6a11353576954572bbbe18ed690f2bad",
            "input": "There is a commonly held belief that the development of a hernia can be attributed to a single strenuous or traumatic event. Hence, many litigants are successful in compensation claims, causing mounting financial burdens on employers, the courts, insurance companies and the tax-payer. However, there is very little scientific evidence to support this assertion. The aim of this study was to ascertain whether there was any causal link in this process.', 'A total of 133 new patients with 135 abdominal herniae of all varieties (115 inguinal, 3 femoral, 9 umbilical, 4 incisional, and 4 ventral or epigastric), of which 25 were recurrent received structured questionnaires on arrival in the surgical clinic. These questionnaires covered all possible aetiological factors for hernia development (type of work, COAD, smoking, pregnancy, obesity, chronic bladder outflow obstruction, previous surgery including appendicectomy), in addition to any possible attribution to a single strenuous or traumatic event. We then reviewed the GP records in the surgery of all patients who answered positively to the latter possible cause.', 'In the study group, 119 (89%) reported a gradual onset of symptoms. Of the 15 (12 male, 3 female; 11%) who believed that their hernia might be related to a single strenuous or traumatic event, 5 had no other aetiological factors. However, not one of the 15 was found to have contemporaneous forensic medical evidence to support their possible claim.",
            "output": [
                "Is it highly unlikely that the development of an abdominal wall hernia can be attributable to a single strenuous event?"
            ]
        },
        {
            "id": "task847-a75ab7da3b16417591867da2980b7090",
            "input": "Cytokines and chemokines potentially modulate postoperative immune response. Association of circulating cytokines and chemokines with postoperative infectious complications after pancreaticoduodenectomy was evaluated.', 'Plasma concentrations of interleukin (IL) 6, IL-10, IL-8, macrophage chemoattractant protein 1, heat shock protein 70, and amylase, as well as amylase levels in peritoneal exudative fluid, were measured perioperatively in 60 consecutive patients who underwent pancreaticoduodenectomy.', 'Of the 60 patients, 27 patients had surgical site infection (SSI), including peritoneal infection in all, intra-abdominal abscess in 14, and radiologically visualized pancreatic leakage in 6. Postoperative plasma levels of IL-6, IL-8, and macrophage chemoattractant protein 1, as well as peritoneal amylase levels, were significantly higher in patients with SSI than in those without SSI (P < 0.05). Nonpancreatic cancer as a histopathologic diagnosis, high pancreatic juice flow, and increased levels of IL-6 and IL-8 were independently associated with SSI (P < 0.05) in multiple logistic regression analysis. Plasma levels of IL-6 and IL-10 among patients with SSI were significantly higher in those with pancreatic leakage than in those without leakage.",
            "output": [
                "Are increased plasma levels of IL-6 and IL-8 associated with surgical site infection after pancreaticoduodenectomy?"
            ]
        },
        {
            "id": "task847-e52f8fa642274a2e9d65353df9d05135",
            "input": "Catecholamines have anti-inflammatory and anticoagulant properties. Dobutamine is a synthetic catecholamine frequently used in patients with septic myocardial dysfunction. The objective was to determine whether a continuous infusion of dobutamine exerts immunomodulatory effects in healthy volunteers challenged with endotoxin.', 'Prospective, open-label study.', 'Clinical research unit of a university hospital.', 'Sixteen male healthy volunteers.', 'Volunteers received a constant infusion with dobutamine (10 microg.kg.min, n = 8) or physiologic saline (n = 8). All participants were challenged with a bolus injection of endotoxin prepared from Escherichia coli (4 ng/kg). Dobutamine infusion was commenced 1 hr before endotoxin challenge and was continued until 3 hrs thereafter.', 'Dobutamine infusion was associated with an increase in mean arterial blood pressure (peak 122 +/- 5 mm Hg) and heart rate (peak 84 +/- 4 beats/min, both p < .05 vs. saline). Endotoxin injection induced the systemic release of cytokines (tumor necrosis factor-alpha, interleukins-6, -8, and -10) and secretory phospholipase A2, endothelial cell activation (increase in the plasma levels of soluble E-selectin and von Willebrand factor), activation of coagulation (increased plasma levels of soluble tissue factor, F1 + 2 prothrombin fragment, and thrombin-antithrombin complexes), and activation with subsequent inhibition of fibrinolysis (increased plasma concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor type I, and plasmin-alpha2-antiplasmin complexes). None of these responses were influenced by dobutamine.",
            "output": [
                "Does dobutamine influence inflammatory pathways during human endotoxemia?"
            ]
        },
        {
            "id": "task847-8ffb89b63be24c1aa5210cd181e2c30a",
            "input": "It is often suggested that immigrants with long-term pain do not benefit from rehabilitation to the same extent as native Swedish patients. In this study, an 8-week rehabilitation programme was evaluated according to its adaptation for immigrants.', \"To establish whether there is a difference between immigrants and native Swedes concerning: (i) return-to-work, the patients' own estimation and their actual ability; (ii) higher level of activity; (iii) reduction in pain and analgesic use.\", 'A total of 67 patients with persistent non-malignant pain completed the rehabilitation programme. Thirty (45%) of the patients were immigrants.', 'A 1- and a 3-year follow-up were made to compare the outcome between the 2 groups.', \"There was no significant difference in the return-to-work rate between immigrants and native Swedes. However, the patients' prediction of their ability to return to work was higher among the non-immigrants. The level of activity was lower and pain intensity and use of analgesics were higher among the immigrants than the non-immigrants.",
            "output": [
                "Does ethnic background influence outcome for return-to-work in work-related interdisciplinary rehabilitation for long-term pain : 1- and 3-year follow-up?"
            ]
        },
        {
            "id": "task847-ddb9c3d50c324533856812ba495c647f",
            "input": "To ascertain whether different hormonal treatment protocols could affect metaphase II (MII) spindle morphology, meiotic spindle organization was detected in prepubertal mouse oocytes matured under conditions allowing spontaneous, FSH- or epidermal growth factor (EGF)-dependent meiotic maturation.', 'Oocyte-cumulus complexes (OCCs) were matured either spontaneously (control; n=270) or in the presence of hypoxanthine (Hx) plus FSH (n=400) or EGF (n=370). Spindles were detected by immunofluorescence analysis. In vivo ovulated (IVO) oocytes were processed similarly.', 'IVO oocytes displayed spindles underlying the oolemma and with focused poles marked by spots of gamma-tubulin, whereas the majority (89%) of control oocytes had barrel-shaped spindles, positioned away from the oolemma, and with gamma-tubulin distributed along microtubules. Similar configuration/localization was found in 85% of the oocytes matured in vitro in the presence of Hx and FSH. In the presence of Hx-EGF, 35% of the oocytes showed spindles with an IVO-like configuration, although gamma-tubulin was homogeneously distributed throughout microtubules. Independently of spindle shape, 52% of EGF-stimulated oocytes had spindles positioned near the oolemma, in comparison to just 24% of FSH-treated and 13% of control oocytes.",
            "output": [
                "Is meiotic spindle configuration differentially influenced by FSH and epidermal growth factor during in vitro maturation of mouse oocytes?"
            ]
        },
        {
            "id": "task847-7a31ae59f12b438eb6b050eaf4a78092",
            "input": "Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from triglyceride stores in adipocytes. The aim of the present study was to investigate the role of the HSL gene promoter variant C-60G, a polymorphism which previously has been associated with reduced promoter activity in vitro, in obesity and type 2 diabetes.', 'We genotyped two materials consisting of obese subjects and non-obese controls, one material with offspring-parents trios, where the offspring was abdominally obese and one material with trios, where the offspring had type 2 diabetes or impaired glucose homeostasis. HSL promoter containing the HSL C-60G G-allele was generated and tested against a construct with the C-allele in HeLa cells and primary rat adipocytes. HSL mRNA levels were quantified in subcutaneous and visceral fat from 33 obese subjects.', 'We found that the common C-allele was associated with increased waist circumference and WHR in lean controls, but there was no difference in genotype frequency between obese and non-obese subjects. There was a significant increased transmission of C-alleles to the abdominally obese offspring but no increased transmission of C-alleles was observed to offspring with impaired glucose homeostasis. The G-allele showed reduced transcription in HeLa cells and primary rat adipocytes. HSL mRNA levels were significantly higher in subcutaneous compared to visceral fat from obese subjects.",
            "output": [
                "Is the hormone-sensitive lipase C-60G promoter polymorphism associated with increased waist circumference in normal-weight subjects?"
            ]
        },
        {
            "id": "task847-5f2596ba2980496c9c2ffd244400b058",
            "input": "Vascular endothelial growth factor (VEGF) has been suggested to enhance glucose transport across the blood-brain barrier, thereby increasing brain glucose supply. Increased brain glucose concentration is known to suppress food intake and to decrease body mass via action on hypothalamic regulation centers. Based on the crucial role of VEGF on brain glucose supply, we hypothesized that higher VEGF concentrations are associated with lower food intake and body mass in humans.', 'Intending to investigate subjects with high variance of blood glucose, we examined patients with type 2 diabetes mellitus. Our hypothesis was tested in a population-based cohort of 190 subjects with type 2 diabetes. Plasma VEGF levels in conjunction with other parameters known to modulate food intake were measured and subsequently correlated with food intake patterns at a breakfast buffet as well as with body mass.', 'We found that subjects with higher concentrations of plasma VEGF had 17% less carbohydrate intake (P=0.003) and 4.8% lower body mass (P=0.017) than those with lower VEGF concentrations. Intake of protein and fat did not correlate with VEGF concentrations. These associations of plasma VEGF were confirmed in multiple linear regression analyses controlling for several parameters interacting with food intake.",
            "output": [
                "Does high plasma VEGF relate to low carbohydrate intake in patients with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-4785d8e666e8425a934263fcd227f871",
            "input": "The basic mechanisms underlying the association between early life maternal separation and adulthood psychiatric disorders are largely unknown. One possible candidate is the central serotonergic system, which is also abnormal in psychiatric illnesses. Neuroadaptational changes in serotonergic transporter and serotonergic 1A receptors may underlie links between early life stress and adulthood psychiatric disorders.', 'The aim of this study was to investigate the consequences of a rat model of maternal separation on serotonergic transporter and serotonergic 1A receptor densities and function in adult rat forebrain.', 'Rat pups were separated from dams from postnatal day 2 to postnatal day 14, each day, for zero time, 15 min and 180 min to determine the time-course of effects. A non-handled group was added to control for the effects of handling by an experimenter compared with the animal facility-reared group. Quantitative [(125)I]3beta-(4-iodophenyl)tropan-2beta-carboxylic acid methyl ester and [(125)I]-mPPI autoradiography was used to determine serotonergic transporter and serotonergic 1A densities, respectively. Adult rats were challenged with saline or serotonergic 1A agonist (+) 8-hydroxy-2-(di-n-propylamino)tetralin, 0.4 mg/kg, s.c.) and plasma adrenocorticotropic hormone and corticosterone were determined.', 'serotonergic transporter and serotonergic 1A densities were significantly lower in the non-handled group in the paraventricular, arcuate, dorsomedial and ventromedial nuclei of the hypothalamus. The non-handled group also displayed lower serotonergic transporter and serotonergic 1A densities in the basolateral anterior, basolateral ventral and basomedial amygdaloid nuclei. Serotonergic transporter densities were also decreased in the CA3 area of the hippocampus in the non-handled group. In contrast, the maternal separation 15 min group displayed the highest serotonergic transporter and serotonergic 1A densities in the basomedial nucleus of amygdala, basolateral anterior nucleus of amygdala, basolateral ventral nucleus of amygdala and basomedial nucleus of amygdala amygdaloid nuclei.",
            "output": [
                "Does maternal separation alter serotonergic transporter densities and serotonergic 1A receptors in rat brain?"
            ]
        },
        {
            "id": "task847-2eb2aef9c0654c038dd0cffb3bdeb6d4",
            "input": "To examine whether total and abdominal adiposity are risk factors for the development of chronic heart failure (CHF) in older men and women.', 'Prospective, longitudinal cohort: The Health, Aging and Body Composition study.', 'Memphis, Tennessee, and Pittsburgh, Pennsylvania, metropolitan areas.', 'Three thousand seventy-five well-functioning community-dwelling older adults aged 70 to 79.', 'Body composition using dual energy X-ray absorptiometry, visceral adipose tissue area using computed tomography, adjudicated CHF.', 'Of the remaining (640 participants excluded from original group of 3,075) 2,435 participants (1,081 men, 1,354 women) without coronary heart disease or CHF at baseline, there were 166 confirmed diagnoses of CHF during the median+/-standard deviation (SD) follow-up of 6.1+/-1.4 years. After adjustment for age, race, sex, site, education, smoking, and chronic obstructive pulmonary disorder, all adiposity variables (body mass index (BMI), adipose tissue mass, percentage body fat, waist-to-thigh ratio, waist circumference, and visceral and subcutaneous abdominal adipose tissue) were significant predictors of the development of CHF. In a model that included waist circumference and BMI, waist circumference was associated with incident CHF (hazard ratio (HR)=1.27, 95% confidence interval (CI)=1.04-1.54 per SD increase, P=.02), but BMI was not (HR=1.08, 95% CI=0.86-1.35). When waist circumference and percentage fat were included together, both variables were significant predictors of CHF (waist: HR=1.17, 95% CI=1.00-1.36 per SD increase, P=.05; percentage fat: HR=1.47, 95% CI=1.16-1.87 per SD increase, P=.002). Stepwise adjustment for inflammation, hypertension, insulin resistance, and diabetes mellitus did not decrease the relative risk of a greater waist circumference for the development of CHF (all HR=1.27-1.32, 95% CI=1.02-1.61 per SD increase).",
            "output": [
                "Is abdominal obesity an independent risk factor for chronic heart failure in older people?"
            ]
        },
        {
            "id": "task847-b025e93f87594da6aa8138a995e73223",
            "input": "To study the association between impaired fasting glucose (IFG) and arterial stiffness in older adults.', 'Cross-sectional population-based study.', 'The Rotterdam Study, a Dutch population-based cohort study.', 'Two thousand nine hundred eighty-seven subjects aged 60 and older.', 'Arterial stiffness assessed by measuring common carotid arterial distensibility and glucose status classified into three categories: normal fasting glucose (NFG) (fasting glucose <6.1 mmol/L), IFG (fasting glucose 6.1-6.9 mmol/L), and diabetes mellitus (DM).', 'In the total cohort, common carotid distensibility decreased with increasing impairment of glucose metabolism. Subjects younger than 75 with IFG were comparable with subjects with NFG with respect to arterial stiffness. Subjects aged 75 and older with IFG had stiffer arteries than subjects with NFG, reaching the same arterial stiffness as subjects with DM. For subjects younger than 75, mean difference in distensibility coefficient between subjects with NFG and with IFG was 0.1 (95% confidence interval (CI)=-0.04-0.05, P=.88) and between subjects with NFG and with DM was 1.2 (95% CI=0.7-1.7, P<.001). For subjects aged 75 and older, the mean difference between these groups was 0.7 (95% CI=0.2-1.2, P=.007) and 0.8 (0.3-1.4; P=.002), respectively. In the total cohort, fasting glucose was strongly associated with carotid distensibility (beta-coefficient=-0.29, P<.001).",
            "output": [
                "Is impaired fasting glucose associated with increased arterial stiffness in elderly people without diabetes mellitus : the Rotterdam Study?"
            ]
        },
        {
            "id": "task847-233a4ab7f7a849359a3d790dc1ff40d5",
            "input": "To determine whether objective measures of sleep correlate with plasma levels of the proinflammatory cytokine interleukin (IL)-6 and the procoagulant marker fibrin D-dimer in caregivers of patients with dementia.', 'Cross-sectional study.', \"Subjects' homes.\", 'Sixty-four community-dwelling spousal caregivers (69% women, mean age+/-standard deviation 72+/-9) and 36 sex-matched noncaregiving controls.', 'All participants underwent in-home full-night polysomnography. Demographic and lifestyle factors, depression, diseases, and medication that could affect inflammation, coagulation, and sleep were controlled for in analyses regressing sleep variables and caregiver status and their interaction on plasma levels of IL-6 and D-dimer.', 'Caregivers had higher levels of D-dimer (781+/-591 vs 463+/-214 ng/mL, P=.001) and IL-6 (1.42+/-1.52 vs 0.99+/-0.86 pg/mL, P<.06) and lower levels of total sleep time (369+/-70 vs 393+/-51 minutes, P=.049) and sleep efficiency (77+/-11 vs 82+/-9%, P=.04) than controls. After controlling for age and body mass index, longer wake time after sleep onset (change in coefficient of determination (DeltaR2)=0.039, P=.04) and the interaction between caregiver status and higher apnea-hypopnea index (DeltaR2=0.054, P=.01) were predictors of IL-6. Controlling for age, caregiver status independently predicted D-dimer levels (DeltaR2=0.047, P=.01). Controlling for age and caregiver status, lower sleep efficiency (DeltaR2=0.032, P=.03) and the interaction between caregiver status and more Stage 2 sleep (DeltaR2=0.037, P=.02) independently predicted plasma D-dimer levels.",
            "output": [
                "Is poor sleep associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-a5a46e59c18546a692c574df708cc76c",
            "input": "To investigate the six-month recommended follow-up after mass screening of Pap smears because of the absence of endocervical columnar cells (ECC-) or ECC+ smears with atypical squamous or glandular cells of undetermined origin (ASCUS/AGUS) or low-grade squamous or glandular intraepithelial lesions (LSIL/LGIL) in a Dutch mass screening cervical cancer programme.', 'Data were extracted from computerised medical records of national representative Dutch general practices. We have studied the attendance at and the outcome of the subsequent Pap smears after a 6-month recommendation.', 'The six-month follow-up was linked to 8.7% of the Pap smears (n = 1,002); 77.6% were without endocervical columnar cells (ECC-). Clear differences were found between the follow-up of ECC+ and ECC- smears; after 36 weeks of follow-up of 43.5% the women had an ECC- smear and 66.9% had other conditions. For initial ECC- Pap smears, 84.1% had no abnormalities in the subsequent Pap smear; for initial ECC+ Pap smears, in about 64% of the cases no abnormalities were found (p < 0.0001).",
            "output": [
                "Is loss to follow-up of cervical smears without endocervical columnar cells disturbing?"
            ]
        },
        {
            "id": "task847-71e3cdc644ba47769d5dabc02a6b0f5b",
            "input": "The aim of this study was to evaluate long-term allograft salvage rates of patients with steroid refractory allograft rejection after kidney transplantation and to identify factors indicating a successful outcome.', 'Fifty patients with continuing rejection after high-dose steroids were included in the study. Baseline immunosuppression was switched from cyclosporine to tacrolimus in all patients. Twenty patients additionally received OKT3 as antirejection therapy. Patients having received a cadaveric renal transplant in 1995, excluding patients with steroid resistant rejection, were chosen as a control cohort.', 'Patient survival rates were 96% (n = 48) and 90% (n = 45) and allograft survival rates were 66% (n = 33) and 62% (n = 31) after 5 and 7 years following steroid refractory renal allograft rejection. Graft survival within the control cohort was 73% after 5 years and 69% after 7 years. Creatinine clearance increased from 20 +/- 15 ml/min/1.73 m2 at the start of tacrolimus therapy to 37 +/- 29 ml/min/1.73 m2 and to 32 +/- 26 ml/min/1.73 m2 after 5 and 7 years. OKT3 treatment predicted successful rescue therapy (p = 0.005 and p = 0.04 after 5 and 7 years).",
            "output": [
                "Is oKT3 therapy in addition to tacrolimus associated with improved long-term function in patients with steroid refractory renal allograft rejection?"
            ]
        },
        {
            "id": "task847-150a1f830a0245f4a8a4c4079861c5cc",
            "input": "Exogenous leptin markedly decreased plasma paraoxonase (PON1) activity in rats. Hyperleptinemia and decreased PON1 activity have previously been demonstrated in uremia. Therefore, we investigated the relationship between leptin level and PON1 activity in hemodialysis (HD) patients.', 'Leptin and PON1 were determined in 40 HD patients and 40 age-matched controls with similar body mass index (BMI).', 'Leptin was higher (p < 0.001) and PON1 activity was lower (p < 0.001) in HD patients than in controls. PON1 and PON1/HDL ratio was higher in HD patients with BMI >25 kg/m2 than in HD patients with BMI <25 kg/m2. It was not due to a difference in frequency of high activity phenotype of PON1 among subgroups of HD patients. There was no similar difference in controls. Spearman analysis showed a significant correlation between leptin and PON1 activity (p < 0.02), BMI (p < 0.001), triglyceride (TG) (p < 0.03), and Kt/V (-0.323, p < 0.03), but multiparametric regression analysis did not reveal it. PON1 activity depended on BMI in both models. In controls, leptin correlated with BMI (p < 0.001) and TG (p < 0.002) but not PON1 activity. A slight decrease in leptin concentration and PON1 activity during HD was observed.",
            "output": [
                "Is hyperleptinemia responsible for decreased paraoxonase activity in hemodialysis patients?"
            ]
        },
        {
            "id": "task847-2b6c011b9a21420fba056d6a6a999691",
            "input": "Organic cation transporters 1-3 (OCT1-3; Slc22a1-3) mediate the membrane transport of organic cations in the kidney. We previously reported that rat (r)OCT2 expression in the kidney was regulated by testosterone. In this study, we examined the transcriptional mechanisms underlying the testosterone-dependent regulation of rOCT2 expression.', 'Approximately 3000-bp fragments of the rOCT1-3 promoter region were isolated, and promoter activities were measured in the renal epithelial cell line LLC-PK1 with the coexpression of rat androgen receptor.', 'Among reporter constructs tested, only rOCT2 promoter activity was stimulated by testosterone. This stimulation was suppressed by nilutamide, an antiandrogen drug. Reporter assays using deletion constructs and mutational constructs of putative androgen response elements (ARE) in the rOCT2 promoter region suggested that two AREs, located at approximately -3000 and -1300, respectively, play an important role in the induction by testosterone.",
            "output": [
                "Is androgen receptor responsible for rat organic cation transporter 2 gene regulation but not for rOCT1 and rOCT3?"
            ]
        },
        {
            "id": "task847-b2d53122e73f48489082058863d8a50d",
            "input": "The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial growth factor (VEGF) and interleukin-2 (IL-2) were embedded in the device as sample therapeutic proteins, and their release and bioactivity were compared to that achieved previously with interferon-gamma (IFN-gamma).', 'A photo-cross-linkable biodegradable macromer consisting of acrylated star(epsilon-caprolactone-co-D,L-lactide) was prepared. VEGF, IL-2, and IFN-gamma were co-lyophilized with serum albumin and trehalose at different ratios and were then embedded into the elastomer by photo-cross-linking the lyophilized particles in a macromer solution. The protein mass and the bioactivity in the release supernatant were measured by enzyme-linked immunosorbent and cell-based assays.', 'VEGF, IL-2, and IFN-gamma were released at the same, nearly constant rate of 25.4 ng/day for over 18 days. Using the optimum elastomer formulation, the release profiles of the proteins were essentially identical, and their rates were linear and constant. Cell-based bioactivity assays showed that 70 and 88% of the released VEGF and IL-2, respectively, were bioactive. The rate of protein release can be adjusted by changing the trehalose loading concentration in the elastomer matrix without altering the linear nature of the protein release kinetics. The elastomeric device degraded in PBS buffer within 85 days.",
            "output": [
                "Are osmotic-driven release kinetics of bioactive therapeutic proteins from a biodegradable elastomer linear , constant , similar , and adjustable?"
            ]
        },
        {
            "id": "task847-8764120891494eec8760301f7528d667",
            "input": "The objective of this study was to compare the effect of air abrasion (KCP 2000), acid etching (37% phosphoric acid), and the combination of both procedures on the shear bond strength and microleakage of a light-cured pit-and-fissure sealant to the enamel of human primary molar teeth.', 'Noncarious extracted human primary molars were randomly divided into 4 groups in preparation for enamel bonding. The enamel surface was treated as follows for each group: (1) group 1 (control group); (2) group 2 (acid etch group); (3) group 3 (KCP [Kinetic Cavity Preparation System] group); and (4) group 4 (KCP and acid etch group). Delton, a light-cured pit-and-fissure sealant, was then applied to the occlusal surface after conditioning. The bonded specimens were maintained in distilled water at 37 degrees C+/-2 degrees C for 7 days, after which they were subjected to thermocycling followed by shear bond testing. Microleakage was determined by immersing the prepared teeth in 50% silver nitrate dye followed by sectioning and calculation of dye penetration.', 'The mean shear bond strength of the KCP+acid etch group exhibited nearly 50% higher bond strength than the acid etch group (P<.01). In addition, specimens bonded to enamel conditioned only with acid etch exhibited bond strengths that were nearly twice that of those conditioned with the KCP system alone. No significant difference was noted between the air abrasion and control groups.",
            "output": [
                "Do microleakage and bond strength of sealant to primary enamel comparing air abrasion and acid etch techniques?"
            ]
        },
        {
            "id": "task847-ae8f76b31a244de79ae76c6cdc76f2f9",
            "input": "Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at micro-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors.', 'Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol.', 'Similar to prototypical micro-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p < .01); in contrast, the two highest doses reduced it (p < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorphine (p < .001) but did not affect the inhibition of ethanol drinking induced by 3.0 mg/kg of buprenorphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 microg/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine.",
            "output": [
                "Does buprenorphine reduce alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system?"
            ]
        },
        {
            "id": "task847-0f4a481225c740a79bf4255c8186b3a9",
            "input": "People diagnosed with cancer often self-administer complementary and alternative medicines (CAMs) to supplement their conventional treatments, improve health, or prevent recurrence. Flor-Essence and Essiac Herbal Tonics are commercially available complex mixtures of herbal extracts sold as dietary supplements and used by cancer patients based on anecdotal evidence that they can treat or prevent disease. In this study, we evaluated Flor-Essence and Essiac for their effects on the growth of human tumor cells in culture.', 'The effect of Flor-Essence and Essiac((R)) herbal tonics on cell proliferation was tested in MCF-7, MDA-MB-436, MDA-MB-231, and T47D cancer cells isolated from human breast tumors. Estrogen receptor (ER) dependent activation of a luciferase reporter construct was tested in MCF-7 cells. Specific binding to the ER was tested using an ICI 182,780 competition assay.', 'Flor-Essence and Essiac herbal tonics at 1%, 2%, 4% and 8% stimulated cell proliferation relative to untreated controls in both estrogen receptor positive (MCF-7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDA-MB-436) cell lines. Exposure to the tonics also produced a dose-dependent increase in ER dependent luciferase activity in MCF-7 cells. A 10(-7) M concentration of ICI 182,780 inhibited the induction of ER dependent luciferase activity by Flor-Essence and Essiac, but did not affect cell proliferation.",
            "output": [
                "Do essiac and Flor-Essence herbal tonics stimulate the in vitro growth of human breast cancer cells?"
            ]
        },
        {
            "id": "task847-a9a3f8dfe1524da5b0620e8f1a9fe4bf",
            "input": "The human inspiratory muscles respond to a brief occlusion of the upper airway during inspiration with a profound short-latency reflex inhibition. This inhibition contrasts with the excitatory stretch reflex of limb muscles and may protect the airway from aspiration. It was postulated that this reflex would be altered in subjects with obstructive sleep apnea (OSA) who have repetitive upper airway occlusion.', 'Subjects underwent overnight polysomnography, as well as muscle reflex studies. For the reflex studies (performed during wakefulness), occlusions lasting 250 milliseconds were delivered during inspiration. Surface electromyogram was recorded over the scalenes, parasternal intercostals, and chest wall (overlying diaphragm).', 'Research and sleep laboratories.', 'Nineteen subjects with untreated OSA (9 moderate and 10 severe) and 9 healthy control subjects.', 'In the subjects with severe OSA, the duration of the inhibition was prolonged by at least 25% compared with control subjects. The peak of the inhibitory response for scalenes occurred significantly later for subjects with severe OSA than for control subjects (by 76 +/- 5 ms vs 60 +/- 3 ms [mean +/- SEM], respectively). Onset latencies of the later excitatory response were delayed for scalenes, parasternal intercostals, and chest wall recordings (eg, scalenes: 105 +/- 9 ms for subjects with severe OSA vs 83 +/- 5 ms for control subjects).",
            "output": [
                "Does brief airway occlusion produce prolonged reflex inhibition of inspiratory muscles in obstructive sleep apnea?"
            ]
        },
        {
            "id": "task847-3e20bd6add45447c8219bbd53387002b",
            "input": "To evaluate the efficacy of the commercially available product Mitigator Sting and Bite Treatment in reducing the pain after imported fire ant stings.', 'Twenty-four volunteer subjects were exposed to imported fire ant stings on both fore-arms. The subjects received Mitigator paste on 1 arm and calamine lotion on the opposite arm, in a blinded manner, from 90 seconds to 10 minutes after exposure. Subjects recorded pain on a 100-mm visual analog scale 60 seconds, 20 minutes, and 3 days after exposure. A 2-tailed paired t test was used to compare the difference in reduction of pain over time between the Mitigator-treated arms and the calamine-treated arms.', 'At 60 seconds, the mean visual analog scale pain score was 23.9 mm for the Mitigator group and 24.5 mm for the calamine group. At 20 minutes, the mean score was 7.6 mm (delta = 16.3) for the Mitigator group and 12.7 mm (delta = 11.8) for the calamine group. At 3 days, the mean score was 2.4 mm (delta = 21.5) for the Mitigator group and 2.9 mm (delta = 21.6) for the calamine group. There was no significant difference between groups for change in visual analog scale pain score at 60 seconds, 20 minutes (P = .256), or 3 days (P = .64).",
            "output": [
                "Does treatment of imported fire ant sting with mitigator sting and bite treatment -- a randomized control study?"
            ]
        },
        {
            "id": "task847-f8f83693e9924eccad5465e27db6066b",
            "input": "To investigate the in vivo effect of atrial natriuretic peptide (ANP) and its signaling pathway during orthotopic rat liver transplantation.', 'Rats were infused with NaCl, ANP (5 microg/kg), wortmannin (WM, 16 microg/kg), or a combination of both for 20 min. Livers were stored in UW solution (4 degrees C) for 24 h, transplanted and reperfused. Apoptosis was examined by caspase-3 activity and TUNEL staining. Phosphorylation of Akt and Bad was visualized by Western blotting and phospho-Akt-localization by confocal microscopy.', 'ANP-pretreatment decreased caspase-3 activity and TUNEL-positive cells after cold ischemia, indicating antiapoptotic effects of ANP in vivo. The antiapoptotic signaling of ANP was most likely caused by phosphorylation of Akt and Bad, since pretreatment with PI 3-kinase inhibitor WM abrogated the ANP-induced reduction of caspase-3 activity. Interestingly, analysis of liver tissue by confocal microscopy showed translocation of phosphorylated Akt to the plasma membrane of hepatocytes evoked by ANP.",
            "output": [
                "Is pI 3-kinase pathway responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation?"
            ]
        },
        {
            "id": "task847-a1d49cbe1c35428caf898c51d1e4ac51",
            "input": "Individuals diagnosed with blood-injury phobia respond to venipuncture with strong psychophysiological responses. We investigated whether disgust sensitivity contributes to the fainting response and is associated with parasympathetic activation, as suggested by previous research.', 'Twenty individuals diagnosed with blood-injury phobia (9 with a history of fainting to the sight of blood, 11 without such a fainting history) and 20 healthy controls were compared. Psychophysiological responses and self-report measures of anxiety, disgust, and embarrassment were monitored during rest, a paced breathing task, and venipuncture. In addition, trait disgust sensitivity and blood-injury fears were assessed.', 'Blood-injury phobics reported enhanced anxiety, disgust, and embarrassment during venipuncture. They also experienced heightened arousal, as indicated by heart rate, respiration rate, and minute ventilation. Blood-injury phobics without a fainting history tended toward higher anxiety and disgust scores. There was no evidence for increased parasympathetic activation in either blood-injury phobic subgroup or of an association of disgust and parasympathetic activation.",
            "output": [
                "Does blood-injury phobia with and without a history of fainting : disgust sensitivity explain the fainting response?"
            ]
        },
        {
            "id": "task847-3bb31911f0e2442fba6154776c14e198",
            "input": "Islet function is regulated by islet autonomic nerves. These nerves harbour not only the classical neurotransmitters, acetyl choline and noradrenaline, but also neuropeptides. This study examined whether the neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) and gastrin releasing polypeptide (GRP) contribute to the regulation of insulin secretion in model experiments by using receptor gene deleted mice.', 'Anaesthetized mice with genetic deletion of one of the PACAP receptors (PAC1 receptors) or one of the GRP receptors (GRP receptor) or their wildtype counterparts were given glucose through a gastric gavage (150 mg) or intravenously (0.25, 0.50 or 1 g/kg). Blood samples were taken regularly during the following 120 min (after gastric glucose) or at 1 min (after intravenous glucose) for analysis of glucose and insulin.', 'The insulin response to gastric glucose was suppressed by 66% in PAC1 receptor gene deleted mice in association with impaired glucose elimination, whereas the insulin response to intravenous glucose was impaired by 36% only. The insulin response to glucose was suppressed in GRP receptor gene deleted mice by 24% together with impaired glucose elimination, whereas the insulin response to intravenous glucose was not significantly suppressed.",
            "output": [
                "Is the insulin response to gastric glucose reduced in PAC1 and GRP receptor gene deleted mice?"
            ]
        },
        {
            "id": "task847-795545ffde44446d8b773949f31d45e6",
            "input": "Methionine sulfoxide reduction is an important protein repair pathway that protects against oxidative stress, controls protein function and has a role in regulation of aging. There are two enzymes that reduce stereospecifically oxidized methionine residues: MsrA (methionine-S-sulfoxide reductase) and MsrB (methionine-R-sulfoxide reductase). In many organisms, these enzymes are targeted to various cellular compartments. In mammals, a single MsrA gene is known, however, its product is present in cytosol, nucleus, and mitochondria. In contrast, three mammalian MsrB genes have been identified whose products are located in different cellular compartments.', 'In the present study, we identified and characterized alternatively spliced forms of mammalian MsrA. In addition to the previously known variant containing an N-terminal mitochondrial signal peptide and distributed between mitochondria and cytosol, a second mouse and human form was detected in silico. This form, MsrA(S), was generated using an alternative first exon. MsrA(S) was enzymatically active and was present in cytosol and nucleus in transfected cells, but occurred below detection limits in tested mouse tissues. The third alternative form lacked the active site and could not be functional. In addition, we found that mitochondrial and cytosolic forms of both MsrA and MsrB in Drosophila could be generated by alternative first exon splicing.",
            "output": [
                "Does alternative first exon splicing regulate subcellular distribution of methionine sulfoxide reductases?"
            ]
        },
        {
            "id": "task847-e02622e2d30c423f993ee985f8978196",
            "input": "Poor condition at operation determined by the physiologic POSSUM score is related to postoperative mortality and morbidity of colorectal cancer surgery. This study was designed to analyze the relationship between condition of patients with colorectal cancer at operation and long-term overall survival.', 'A total of 542 patients survived a radical resection for Stages I, II, or III colorectal cancer. Physiologic POSSUM score at surgery, exclusive of age, was calculated for all patients. Mean physiologic POSSUM score was used as cutoff point to determine low-risk and high-risk group patients. A Cox proportional hazard analysis was performed to study the effect of low-risk and high-risk group on overall survival and to identify independent risk factors.', 'Five-year overall survival was significantly higher in low-risk group patients than in high-risk group patients (low-risk group 66.6 percent vs. high-risk group 48.5 percent; P < 0.001). Differences in overall survival also were found when patients in Stages I, II, and III were analyzed separately. Risk factors for overall survival were advanced stage of disease, poor tumor differentiation, mucinous adenocarcinoma, older than age 70 years, and poor condition of the patient at time of operation.",
            "output": [
                "Does pOSSUM predict decreased overall survival in curative resection for colorectal cancer?"
            ]
        },
        {
            "id": "task847-e9cf3c05c86e47269bbcf2736e28f9b4",
            "input": "The Salmonella enterica BarA-SirA, the Erwinia carotovora ExpS-ExpA, the Vibrio cholerae BarA-VarA and the Pseudomonas spp GacS-GacA all belong to the same orthologous family of two-component systems as the Escherichia coli BarA-UvrY. In the first four species it has been demonstrated that disruption of this two-component system leads to a clear reduction in virulence of the bacteria. Our aim was to determine if the Escherichia coli BarA-UvrY two-component system is connected with virulence using a monkey cystitis model.', 'Cystitis was generated in Macaque fascularis monkeys by infecting the bladder with a 1:1 mixture of the uropathogenic Escherichia coli isolate DS17 and a derivative where the uvrY gene had been disrupted with a kanamycin resistance gene. Urine was collected through bladder punctuation at subsequent time intervals and the relative amount of uvrY mutant was determined. This showed that inactivation of the UvrY response regulator leads to a reduced fitness. In similar competitions in culture flasks with Luria Broth (LB) the uvrY mutant rather had a higher fitness than the wild type. When the competitions were done in flasks with human urine the uvrY mutant initially had a lower fitness. This was followed by a fluctuation in the level of mutant in the long-term culture, with a pattern that was specific for the individual urines that were tested. Addition of LB to the different urine competition cultures however clearly led to a consistently higher fitness of the uvrY mutant.",
            "output": [
                "Is the Escherichia coli BarA-UvrY two-component system a virulence determinant in the urinary tract?"
            ]
        },
        {
            "id": "task847-ba21145e6079488e953ed06f22d5e909",
            "input": "Asthma morbidity and mortality is highest among inner-city populations. Suboptimal beliefs about the chronicity of asthma may perpetuate poor asthma control among inner-city asthmatics. This study sought to characterize beliefs about the chronicity of disease and its correlates in a cohort of inner-city adults with persistent asthma.', 'Prospective, longitudinal, observational cohort study.', 'One hundred ninety-eight adults hospitalized with asthma over a 12-month period at an inner-city teaching hospital.', 'Sociodemographics, clinical history, disease beliefs, and self-management behaviors were collected by interview. Information on self-reported use of inhaled corticosteroids (ICS), peak flowmeters, and regular asthma visits was collected during hospitalization, and 1 month and 6 months after discharge.', 'This cohort was predominantly low income and nonwhite, with high rates of prior intubation, oral steroid use, and emergency department visits and hospitalizations. Overall, 53% of patients believed they only had asthma when they were having symptoms, what we call the no symptoms, no asthma belief. Men patients, those > or = 65 years old, and those with no usual place of care had greater odds of having the no symptoms, no asthma belief, and those receiving oral steroids all or most of the time or with symptoms most days had half the odds of having this belief (p < 0.05 for all). The no symptoms, no asthma belief was negatively associated with beliefs about always having asthma, having lung inflammation, or the importance of using ICS, and was positively associated with expecting to be cured. The acute disease belief was associated with one-third lower odds of adherence to ICS when asymptomatic at all three time periods (p < 0.02 for all).",
            "output": [
                "Is no symptoms , no asthma : the acute episodic disease belief associated with poor self-management among inner-city adults with persistent asthma?"
            ]
        },
        {
            "id": "task847-c0245619250a43fdae389b90d9473e7d",
            "input": "The prognostic role of low sputum eosinophils in steroid-na\u00efve, symptomatic asthmatic patients is controversial.', 'To verify whether low sputum eosinophils predict poor response to treatment with inhaled corticosteroids.', 'Sixty-seven symptomatic asthmatic patients with moderate asthma were examined before and after 2 weeks and 4 weeks of treatment with beclomethasone dipropionate, 500 microg bid. None received corticosteroids in the 3 months preceding the study. At each visit, all patients underwent spirometry, methacholine challenge, and sputum induction. The patients recorded symptom scores and peak expiratory flow (PEF) throughout the study.', 'Seventeen patients had low sputum eosinophils despite being symptomatic. Patients with high (> 3%) sputum eosinophils at baseline showed significant improvement in symptoms, pulmonary function, and bronchial hyperresponsiveness after treatment, whereas patients with low sputum eosinophils showed no significant improvement in most clinical and functional outcomes. Among the baseline indexes examined, sputum eosinophils had the highest negative predictive value but low positive predictive value for the response to treatment. Multiple stepwise regression showed that only baseline FEV(1) and sputum eosinophil percentages significantly correlated with changes in FEV(1) after treatment.",
            "output": [
                "Do low sputum eosinophils predict the lack of response to beclomethasone in symptomatic asthmatic patients?"
            ]
        },
        {
            "id": "task847-93ce659c860d44bc8a4c57cbbef0deaf",
            "input": "Cerebral white matter hyperintensities on magnetic resonance imaging (MRI) scans have been associated with vascular disease and late-life depression, both in the general population and in psychiatric patients. Therefore, a cerebrovascular etiology for late-onset depression has been hypothesized. However, longitudinal studies on the causal role of white matter hyperintensities in the development of depressive symptoms in elderly adults are lacking.', 'To investigate the relation between white matter hyperintensities and depressive symptoms in elderly subjects at risk of cardiovascular disease.', 'In the Dutch sample of the PROSPER (PROspective Study of Pravastatine in the Elderly at Risk of cardiovascular disease) cohort, 527 non-demented elderly, all aged 70 years or older, received a cranial MRI scan and the 15-item Geriatric Depression Scale, at baseline and 33 months (SD 1.6) later.', 'Presence of white matter hyperintensities at baseline was not related to baseline depressive symptoms nor to the development of depressive symptoms during follow-up. Moreover, no association was found between progression of white matter lesion volume and progression of depressive symptoms.",
            "output": [
                "Is progression of cerebral white matter lesions associated with development of depressive symptoms in elderly subjects at risk of cardiovascular disease : The PROSPER Study?"
            ]
        },
        {
            "id": "task847-9b56bed1d2a247bc85483a8d9a44c0ac",
            "input": "To investigate the influences of bicortical anchorage on values of natural frequencies of dental implants utilizing the 3-dimensional finite element analysis.', 'Using the commercial code of Solidworks, 3-D models of a screw-shaped dental implant and a mandibular bone segment were generated. After the 3-D implant-bone complex was meshed by ABAQUS software, effects of bicortical anchorage on the buccolingual and axial first-order natural frequencies of the implant were computed.', 'Bicortical anchorage increased both the buccolingual and axial natural frequencies remarkably. As the bicortical anchorage got deeper, the frequencies correspondingly got higher.",
            "output": [
                "Do [ Influence of bicortical anchorage on the natural frequencies of dental implant ]?"
            ]
        },
        {
            "id": "task847-6faa445f864f48c98faac0a709188078",
            "input": "To investigate the effects of substance P on cultured rat osteoclasts.', 'Neurokinin-1 (NK1) receptor expression in osteoclasts was examined by immunohitochemical method, and changes of bone resorption activity caused by substance P and NK1 receptor antagonists were detected by pit formation assay.', 'Immunoreactivity for NK1 receptor was distributed in the cytoplasm of osteoclasts. The average of pit formation areas significantly increased with addition of substance P (10(-7)-10(-4) mol/L) (P < 0.05), but the number of pitformations did not change (P > 0.05). NK1 receptor antagonists inhibited the enhancement of the bone resorption by substance P addition.",
            "output": [
                "Does [ Substance P regulate function of osteoclasts via neurokinin-1 receptor ]?"
            ]
        },
        {
            "id": "task847-a6b1a57e9160492ab8b1d1b13021373d",
            "input": "Aging is associated with reduced secretion of, and down-regulation of receptors for, progesterone (P); yet, P's effects when administered to younger and older animals have not been systematically investigated. Some of P's antianxiety effects may be due to its conversion to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) and its subsequent actions as a positive modulator at GABAA receptor complexes (GBRs).\", 'We investigated whether P administration can decrease anxiety behavior of progestin receptor (PR) knockout (PRKO) or wild-type control mice.', 'P (10 mg/kg) or vehicle (propylene glycol) were administered subcutaneously to intact, female or male wild-type or PRKO mice that were either 9-12 or 18-24 months of age. Behavior in tasks that assess spontaneous activity (activity monitor and roto-rod), free exploration of a novel environment (open field, elevated plus maze, and elevated zero maze), and conflict behavior (mirror chamber, dark-light transition, and punished drinking) were examined 1 h after injection.', 'P significantly decreased anxiety behavior of both PRKO and wild-type mice. P did not alter motor behavior but increased central entries in the open field, time in the open quadrants of the elevated zero maze, time in the mirrored chamber, time in the light compartment of the dark-light transition, and punished drinking in young and old mice. P-administered mice had higher levels of hippocampal 3alpha,5alpha-THP and GABA-stimulated chloride flux than did vehicle-administered PRKO or wild-type mice.",
            "output": [
                "Do progesterone 's effects to reduce anxiety behavior of aged mice require actions via intracellular progestin receptors?"
            ]
        },
        {
            "id": "task847-d6c0783ea8e445b1ad67b329e61071e5",
            "input": "Clinical studies have shown that performance on the serial digit learning test (SDLT) is dependent upon the mesial temporal lobes, which are responsible for learning and its consolidation. However, an effective SDLT performance is also dependent upon sequencing, temporal ordering, and the utilization of mnemonic strategies. All of these processes are among the functions of the frontal lobes; in spite of this, the relationship between SDLT performance and the frontal lobes has not been demonstrated with previously used mapping techniques. The aim of this study was to investigate the areas of the brain that are activated by SDLT performance.', 'Ten healthy, right handed volunteers (mean age, 20.1 years; SD: 3.3) who had 12 years of education were studied with a 1.0 T MR imaging scanner. BOLD (blood oxygen level dependent) contrast and a modified SDLT were used. Activated loci were automatically mapped using a proportional grid.', 'In learning, the most consistent activation was observed in B-a-7 of the right (80%) and the left hemispheres (50%). In recall, the most consistent activation was observed in B-a-7 of the right hemisphere (60%). Activations were observed in 2.5+/-0.97 Talairach volumes in learning, whereas they encompassed 1.7+/-0.95 volumes in recall. The difference between both phases (learning and recall) regarding total activated volume was significant (p < 0.05).",
            "output": [
                "Does learning of serial digits lead to frontal activation in functional MR imaging?"
            ]
        },
        {
            "id": "task847-291040fb156f4265b6e018e46ae6ecc4",
            "input": "Early metastasis in node-negative breast cancer indicates that breast cancer cells obviously can bypass the lymph nodes and disseminate directly hematogenous to distant organs. For this purpose, we evaluated the prognostic value of blood-borne, HER2-positive circulating tumor cells (CTC) in the peripheral blood from 42 breast cancer patients with a median follow-up of 95 months.', 'Cells were isolated by the patented combined buoyant density gradient and immunomagnetic separation procedure and analyzed by immunocytochemistry.', 'We detected one to eight CTCs in the peripheral blood of 17 of 35 patients (48.6%) presenting no overt metastasis. As a positive control, 7 of 7 (100%) patients with metastatic disease presented positive. Healthy persons and patients (n = 32) operated for nonmalignant diseases presented negative for CTCs. The presence and frequency of HER2-positive CTCs correlated with a significantly decreased disease-free survival (P < 0.005) and overall survival (P < 0.05). Interestingly, in 12 patients with HER2-positive CTCs, the primary tumor was negative for HER2 as assessed by immunohistochemical score and fluorescence in situ hybridization.",
            "output": [
                "Do hER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients?"
            ]
        },
        {
            "id": "task847-d11730b1c8c0415f8325feb67afc03b5",
            "input": "Functional stimulation is accompanied by increases in regional cerebral blood flow which exceed metabolic demands under normal circumstances, but it is unknown whether functional stimulation is beneficial or detrimental in the setting of acute ischemia. The aim of this study was to determine the effect of forepaw stimulation during temporary focal ischemia on neurological and tissue outcome in a rat model of reversible focal forebrain ischemia.', 'Sprague-Dawley rats were prepared for temporary occlusion of the right middle cerebral artery (MCA) using the filament model. Cerebral blood flow in the MCA territory was continuously monitored with a laser-Doppler flowmeter. Subdermal electrodes were inserted into the dorsal forepaw to stimulate either the forepaw ipsilateral or contralateral to the occlusion starting 1 minute into ischemia and continuing throughout the ischemic period. A neurological evaluation was undertaken after 24 hours of reperfusion, and animals were then euthanized and brain slices stained with 2,3,5-triphenyltetrazolium chloride. Cortical and striatal damage was measured separately.', 'The cortical and striatal infarct volumes were both significantly reduced in the contralateral stimulated group compared with the ipsilateral stimulated group (48% total reduction). There were no statistically significant differences in the neurobehavioral scores between the 2 groups, or in the laser-Doppler flow measurements from the MCA core.",
            "output": [
                "Does electrical forepaw stimulation during reversible forebrain ischemia decrease infarct volume?"
            ]
        },
        {
            "id": "task847-6a038e32aae64c65ae84f767084fca13",
            "input": "To investigate if cisplatin alters vitamin status and if VR modulates cisplatin induced intestinal apoptosis and oxidative stress in Wistar/NIN (WNIN) male rats.', 'Weanling, WNIN male rats (n = 12 per group) received adlibitum for 17 wk: control diet (20% protein) or the same with 50% vitamin restriction. They were then sub-divided into two groups of six rats each and administered cisplatin (2.61 mg/kg bodyweight) once a week for three wk or PBS (vehicle control). Intestinal epithelial cell (IEC) apoptosis was monitored by morphometry, Annexin-V binding, M30 cytodeath assay and DNA fragmentation. Structural and functional integrity of the villus were assessed by villus height/crypt depth ratio and activities of alkaline phosphatase, lys, ala-dipeptidyl amino-peptidase, respectively. To assess the probable mechanism(s) of altered apoptosis, oxidative stress parameters, caspase-3 activity, and expression of Bcl-2 and Bax were determined.', 'Cisplatin per se decreased plasma vitamin levels and they were the lowest in VR animals treated with cisplatin. As expected VR increased only villus apoptosis, whereas cisplatin increased stem cell apoptosis in the crypt. However, cisplatin treatment of VR rats increased apoptosis both in villus and crypt regions and was associated with higher levels of TBARS, protein carbonyls and caspase-3 activity, but lower GSH concentrations. VR induced decrease in Bcl-2 expression was further lowered by cisplatin. Bax expression, unaffected by VR was increased on cisplatin treatment. Mucosal functional integrity was severely compromised in cisplatin treated VR-rats.",
            "output": [
                "Does chronic low vitamin intake potentiate cisplatin-induced intestinal epithelial cell apoptosis in WNIN rats?"
            ]
        },
        {
            "id": "task847-ff6b7ffe8d4a4746b296d4a9fb875403",
            "input": "To examine the effect of Eubacterium limosum (E. limosum) on colonic epithelial cell line in vitro, and to evaluate the effect of E. limosum on experimental colitis.', 'E. limosum was inoculated anaerobically and its metabolites were obtained. The growth stimulatory effect of the E. limosum metabolites on T84 cells was evaluated by SUDH activity, and the anti-inflammatory effect by IL-6 production. The change in mRNA of toll like receptor 4 (TLR4) was evaluated by real time PCR. Colitis was induced by feeding BALB/C mice with 2.0% dextran sodium sulfate. These mice received either 5% lyophilized E. limosum (n = 7) or control diet (n = 7). Seven days after colitis induction, clinical and histological scores, colon length, and cecal organic acid levels were determined.', 'The E. limosum produced butyrate, acetate, propionate, and lactate at 0.25, 1.0, 0.025 and 0.07 mmol/L, respectively in medium. At this concentration, each acid had no growth stimulating activity on T84 cells; however, when these acids were mixed together at the above levels, it showed significantly high activity than control. Except for lactate, these acids significantly attenuated IL-6 production at just 0.1 mmol/L. In addition, under TNF-alpha stimulation, butyrate attenuated the production of TLR4 mRNA. The treatment with E. limosum significantly attenuated clinical and histological scores of colitis with an increase of cecal butyrate levels, compared with the control group.",
            "output": [
                "Does eubacterium limosum ameliorate experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity?"
            ]
        },
        {
            "id": "task847-a871001dbacb4467bd32e52188b02622",
            "input": "To assess the effects of eccentric work-induced hamstring fatigue on sagittal and transverse plane (axial) knee and ankle biodynamics and kinetics during a running crossover cut directional change (functional pivot shift).', 'A pretest-posttest, single-group intervention experimental design was employed. All data were collected in a biodynamics laboratory.', 'Twenty healthy athletic females were trained for 3 weeks in crossover cutting before testing.', 'Data were sampled during 3 unfatigued and 3 fatigued (20% eccentric isokinetic knee-flexor torque reduction) crossover cut trials. Three-dimensional kinematic and ground reaction-force data were sampled at 200 Hz and 1000 Hz, respectively, and joint moment estimates were calculated. Data were standardized to initial force-plate heelstrike for comparisons of mean differences between conditions using paired t tests with Bonferroni adjustments. Pearson product-moment correlations compared kinematic and eccentric hamstring-torque relationships.', 'During internal rotation phase 1, between heelstrike and impact absorption, mean internal rotation velocity increased by 21.2 degrees /s +/- 114 degrees /s. During internal rotation phase II, mean peak transverse plane knee rotation during propulsion decreased by 3.1 degrees +/- 9 degrees . During internal rotation phase II, mean peak ankle plantar flexor moment onsets occurred 12.7 +/- 53 milliseconds earlier, and this activation demonstrated a moderately positive relationship with the onset of mean peak knee internal rotation during propulsion and a weak negative relationship with mean peak hamstring torque/lean body weight.",
            "output": [
                "Does crossover cutting during hamstring fatigue produce transverse plane knee control deficits?"
            ]
        },
        {
            "id": "task847-8334a71f41df4b4ca91ce5a41bdc3438",
            "input": "The purpose of the present study was to investigate the effect of supplementation with chicken breast extract (CBEX), which was a rich source of carnosine and anserine, on acid-base balance and performance during intense intermittent exercise.', 'Eight male subjects performed intense intermittent exercise that consisted of 10 x 5-s maximal cycle ergometer sprints with a 25-s recovery period between each sprint. The subjects ingested 190 g of the test soup containing either CBEX or a placebo 30 min before the commencement of exercise. Arterial blood samples were collected at rest and during exercise to estimate the carnosine and anserine concentrations, pH, and bicarbonate concentration ([HCO3-]).', 'Concentrations of anserine and its related amino acid significantly increased 30 min after CBEX supplementation, as compared with their values at rest. However, carnosine did not increase significantly. Following CBEX supplementation, the pH was significantly higher (P < 0.05) at the end of exercise, and [HCO3-] was also significantly higher (P < 0.05) during the latter half of exercise and after exercise. There were no significant differences in the total power and mean power of each set between the CBEX and placebo supplemented groups.",
            "output": [
                "Does carnosine and anserine ingestion enhance contribution of nonbicarbonate buffering?"
            ]
        },
        {
            "id": "task847-468277dd980c4160b71a35a3802495d2",
            "input": "Irinotecan is used in the first-line treatment of metastatic colorectal cancer. The UGT1A1-metabolizing enzyme, expressed in liver and colon, is primarily involved in the inactivation of its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Herein, we explored the role of DNA methylation in the silencing of UGT1A1 gene expression in colon cancer and its influence on cellular SN-38 detoxification.', 'UGT1A1 mRNA was repressed in most primary tumors (41 of 50; 82%) and in three colon cancer cell lines (HCT-116, HCT-15, and COLO-320DM). Bisulfite sequencing of the UGT1A1 gene revealed the aberrant methylation of specific CpG islands in UGT1A1-negative cells. Conversely, hypomethylation was observed in HT-29, HT-115, and LOVO cells that overexpress UGT1A1. Direct methylation of the UGT1A1 promoter resulted in the complete repression of transcriptional activity. Treatment with demethylating and histone deacetylase inhibitor agents had the capacity to reverse aberrant hypermethylation and to restore UGT1A1 expression in hypermethylated UGT1A1-negative cells but not in hypomethylated cells. Loss of UGT1A1 methylation was further associated with an increase in UGT1A1 protein content and with an enhanced inactivation of SN-38 by 300% in HCT-116 cells.",
            "output": [
                "Is irinotecan inactivation modulated by epigenetic silencing of UGT1A1 in colon cancer?"
            ]
        },
        {
            "id": "task847-62b82c448bda45af9a64053ad03bcab9",
            "input": "Several methods may enhance the inhalational induction of anesthesia. In this randomized double-blind study, we evaluated the speed of induction of anesthesia with sevoflurane with or without pre-oxygenation.', 'Fifty-four patients scheduled for hysteroscopy received for 10 min air or 100% oxygen via a facemask followed by > or = 7% sevoflurane in 100% oxygen. During the first 300 s of sevoflurane administration, bispectral index (BIS) values were recorded every 30 s in all patients. In 14 patients, seven in each group, BIS, endtidal CO(2), tidal volume, respiratory rate, SpO(2), and heart rate were recorded every minute during the pre-induction period and every 30 s during the first 5 min of sevoflurane administration.', 'The BIS, endtidal CO(2), tidal volume and respiratory rate did not differ between the oxygen or air breathing groups (P = 0.696, P = 0.999, P = 0.388, and P = 0.875, respectively), though the oxygen group exhibited lower tidal volumes by 16-20%. The SpO(2) and heart rates were higher in the oxygen breathing group (P < 0.001 and P = 0.042, respectively). During sevoflurane administration, BIS values were lower in the oxygen group vs. the group breathing air, in particular at 90, 120, 150, 180 and 210 s (P = 0.001, P = 0.001, P = 0.001, P = 0.001 and P = 0.030, respectively). The endtidal CO(2) and the tidal volumes between the groups did not differ. The two groups differed in the SpO(2) and the heart rates during induction (P = 0.004 and 0.003, respectively).",
            "output": [
                "Does pre-oxygenation enhance induction with sevoflurane as assessed using bispectral index monitoring?"
            ]
        },
        {
            "id": "task847-9d272fff3a594d6eac64ebc60746686b",
            "input": "Adipose tissue is closely associated with angiogenesis, but the mechanisms are not fully understood. Some of the adipocyte-derived cytokines are hypothesized to play an important role in angiogenesis. We evaluated tube formation of human umbilical vascular endothelial cells (HUVECs) cultured in type I collagen gel when overlaid with the supernatant of 3T3-L1 cell culture, and expression of tube-forming factor(s) in 3T3-L1 cells with or without pioglitazone. We also studied plasma growth factor levels in patients with type 2 diabetes mellitus treated with pioglitazone.', 'The supernatant of 3T3-L1 cells increased tube formation of HUVECs by 9.03-fold of control. Reverse transcription-polymerase chain reaction showed that hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) mRNA were expressed in 3T3-L1 cells. Western blot analysis also demonstrated HGF and VEGF protein expression. When 3T3-L1 cells were treated with 100 nM small interfering RNAs (siRNAs) for HGF, the HGF mRNA and protein were suppressed. The VEGF mRNA and protein in the cells were also suppressed by siRNA for VEGF. The supernatant of 3T3-L1 cells treated with HGF siRNA suppressed tube formation of HUVECs by 61% compared with the supernatant of cells treated with control siRNA. Addition of VEGF siRNA resulted in no significant changes. The supernatant conditioned with pioglitazone further promoted the tube formation. Pioglitazone enhanced HGF mRNA expression in 3T3-L1 cells. After 12 weeks of pioglitazone treatment, the changes of plasma HGF levels in patients treated with pioglitazone were significantly higher than those in control.",
            "output": [
                "Does hepatocyte growth factor secreted by cultured adipocytes promote tube formation of vascular endothelial cells in vitro?"
            ]
        },
        {
            "id": "task847-d3ab5403cb0347aba44cadddd18d6010",
            "input": "To determine whether treatment with corticosteroids decreases the incidence of postextubation airway obstruction in an adult intensive care unit.', 'Clinical experiment.', 'Adult medical and surgical intensive care unit of a teaching hospital.', 'One hundred twenty-eight patients who were intubated for >24 hrs with a cuff leak volume <24% of tidal volume and met weaning criteria.', ': Patients were randomized into a placebo group (control, n = 43) receiving four injections of normal saline every 6 hrs, a 4INJ group (n = 42) receiving four injections of methylprednisolone sodium succinate, or a 1INJ group (n = 42) receiving one injection of the corticosteroid followed by three injections of normal saline. Cuff volume was assessed 1 hr after each injection, and extubation was performed 1 hr after the last injection. Postextubation stridor was confirmed by examination using bronchoscopy or laryngoscopy.', 'The incidences of postextubation stridor were lower both in the 1INJ and the 4INJ groups than in the control group (11.6% and 7.1% vs. 30.2%, both p < .05), whereas there was no difference between the two treated groups (p = .46). The cuff leak volume increased after the second and fourth injection in the 4INJ group and after a second injection in the 1INJ group compared with the control group (both p < .05).",
            "output": [
                "Does intravenous injection of methylprednisolone reduce the incidence of postextubation stridor in intensive care unit patients?"
            ]
        },
        {
            "id": "task847-6ec251daef434481a29037246306f4c7",
            "input": "The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from anti-retroviral-naive patients in Europe.', 'The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype.', 'Few dissimilarities were found. An increased genetic barrier was calculated for I82A (subtypes C and G), V108I (subtype G), V118I (subtype G), Q151M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P < 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes.",
            "output": [
                "Is the calculated genetic barrier for antiretroviral drug resistance substitutions largely similar for different HIV-1 subtypes?"
            ]
        },
        {
            "id": "task847-fbee546550c8445db8ed990476642db8",
            "input": "Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily and are key regulators of fatty acid oxidation (FAO) in the heart. Systemic carnitine deficiency (SCD) causes disorders of FAO and induces hypertrophic cardiomyopathy with lipid accumulation. We hypothesized that activation of PPARalpha by fenofibrate, a PPARalpha agonist, in addition to conventional L-carnitine supplementation may exert beneficial effects on the lipotoxic cardiomyopathy in juvenile visceral steatosis (JVS) mouse, a murine model of SCD.', 'Both wild-type (WT) and JVS mice were fed a normal chow, 0.2% fenofibrate containing chow (FE), a 0.1% L-carnitine containing chow (CA) or a 0.1% L-carnitine + 0.2% fenofibrate containing chow (CA + FE) from 4 weeks of age. Four to 8 animals per group were used for each experiment and 9 to 11 animals per group were used for survival analysis.', 'At 8 weeks of age, JVS mice exhibited marked ventricular hypertrophy, which was more attenuated by CA + FE than by CA or FE alone. CA + FE markedly reduced the high plasma and myocardial triglyceride levels and increased the low myocardial ATP content to control levels in JVS mice. In JVS mice, myocardial 1,2-diacylglycerol (DAG) was significantly increased and showed a distinct fatty acid composition with elevation of 18:1(n-7,9) and 18:2(n-6) fatty acids compared with that in WT mice. CA + FE significantly altered the fatty acid composition of DAG and inhibited the membrane translocation of cardiac protein kinase C beta2 in JVS mice. Furthermore, CA + FE prevented the progressive left ventricular dysfunction and dramatically improved the survival rate in JVS mice (survival rate at 400 days after birth: 89 vs. 0%, P < 0.0001).",
            "output": [
                "Does combined therapy with PPARalpha agonist and L-carnitine rescue lipotoxic cardiomyopathy due to systemic carnitine deficiency?"
            ]
        },
        {
            "id": "task847-246a52e6de1c41faa7abc2c7aeee58d0",
            "input": "hMena (ENAH), a cytoskeleton regulatory protein involved in the regulation of cell motility and adhesion, is overexpressed in breast cancer. The aim of this study was to define at what stage of breast carcinogenesis hMena is overexpressed and to correlate hMena overexpression with established prognostic factors in breast cancer, focusing on human epidermal growth factor receptor-2 (HER-2).', 'hMena expression was assessed immunohistochemically in a prospective cohort of cases (n = 360) encompassing a highly representative spectrum of benign breast diseases associated with different risk of transformation, in situ, invasive, and metastatic tumors. Correlations with conventional pathologic and prognostic variables, such as proliferation index, hormonal receptor status, and HER-2 overexpression, were also evaluated. In vitro experiments were done to study the effect of neuregulin-1 and Herceptin treatments on hMena expression.', 'hMena protein is undetectable in normal breast and is weakly expressed in a small percentage of low-risk benign diseases (9%), but displays a progressive and significant increase of positivity in benign lesions at higher risk of transformation (slightly increased risk 43%; moderate increased risk 67%), in in situ (72%), invasive (93%), and metastatic breast cancer (91%). A significant direct correlation with tumor size (P = 0.04), proliferation index (P < 0.0001), and HER-2 overexpression (P < 0.0001) and an inverse relationship with estrogen (P = 0.036) and progesterone receptors (P = 0.001) are found in invasive carcinomas. In vitro experiments show that neuregulin-1 up-regulates, whereas Herceptin down-regulates, hMena expression.",
            "output": [
                "Is the cytoskeleton regulatory protein hMena ( ENAH ) overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors?"
            ]
        },
        {
            "id": "task847-c972e9545dea4967b7e7ceffa91f7bc9",
            "input": "To assess the value of changes in the expression of topoisomerase IIalpha (TopoII) and the proto-oncogene erbB-2 (HER-2) as predictors of relapse-free survival in women with operable breast cancer treated with anthracycline-based neoadjuvant chemotherapy.', 'Seventy-seven patients with primary breast cancer who had undergone neoadjuvant anthracycline-based chemotherapy were included in the present study. TopoII and HER-2 were measured by immunohistochemistry in prechemotherapy and postchemotherapy (at the time of surgery) tumor specimens, and the value of their changes as predictors of relapse-free survival were evaluated by Kaplan-Meier and Cox proportional hazard regression analyses.', 'Neoadjuvant chemotherapy resulted in a significant reduction in the percentage of cells expressing TopoII (P < 0.0001). No significant change was observed for HER-2. TopoII and HER-2 expression before chemotherapy predicted tumor response to treatment. Changes in TopoII expression after chemotherapy were strongly associated with a poor relapse-free survival (P < 0.0001) in a Cox multivariate analysis adjusted for other clinicopathologic prognostic factors.",
            "output": [
                "Does changes of topoisomerase IIalpha expression in breast tumors after neoadjuvant chemotherapy predict relapse-free survival?"
            ]
        },
        {
            "id": "task847-c8d3de0c41fa4957a6c4216253c3d559",
            "input": "Adult attachment theory provides a useful framework for understanding how early developmental experiences affect social processes, associated physiological stress responses, and ultimately, health across the lifespan. The current study examined the effects of attachment orientation on physiological responses to naturalistic social interactions in adolescents.', 'Two-hundred five black (49%) and white high school students (14-16 years; 50% boys) completed a measure of anxious and avoidant attachment, and underwent 1.5 days of ambulatory blood pressure and heart rate (AmBP and AmHR) monitoring while they tracked social experiences.', 'As predicted, individuals with higher avoidant attachment reported fewer interactions with friends (t [299] = -3.18, p < .01) and more anxious adolescents experienced less pleasant interactions both during (t [299] = -3.59, p < .01) and outside of school hours (t [298] = -3.59, p < .01). Individuals who were higher in anxious attachment showed augmented ambulatory diastolic and systolic blood pressure (AmDBP, AmSBP; both p < .05) in conjunction with current or recent interactions with friends. More avoidant adolescents exhibited augmented AmDBP responses to social conflict (p < .05).",
            "output": [
                "Does adolescents ' attachment orientation influence ambulatory blood pressure responses to everyday social interactions?"
            ]
        },
        {
            "id": "task847-add64184bce24cb89ab064dbecfb5951",
            "input": "Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and easily tolerated method of altering cortical physiology. To date, numerous open and sham controlled clinical trials have explored the antidepressant potential of rTMS. In the present study, we investigated clinical trials of high-frequency rTMS (20 Hz) for treatment of refractory depression, and also examined the effect of rTMS on plasma levels of catecholamine metabolites and brain-derived neurotropic factor (BDNF).', 'Twenty-six depressed inpatients who met the DSM-IV criteria for major depressive disorder and had failed to respond to treatment with at least two antidepressant drugs given at adequate doses (above 150 mg/day in an equivalent dose of imipramine) and durations (at least 4 weeks for each drug) were enrolled in this study. Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78 years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography. The plasma levels of BDNF were also measured with the sandwich ELISA method.', 'The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of 20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS. Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by rTMS. The levels of plasma MHPG, but not those of HVA, were significantly reduced after rTMS treatment, and a negative correlation was observed between the change in plasma MHPG levels and the change in scores of agitation. In addition, the plasma levels of BDNF were significantly increased by 23 % in responders and partial responders, but not in nonresponders, after rTMS treatment, and a trend for association was found between the changes in Ham-D scores and changes in plasma BDNF levels in all patients after rTMS treatment.",
            "output": [
                "Does high-frequency repetitive transcranial magnetic stimulation improve refractory depression by influencing catecholamine and brain-derived neurotrophic factors?"
            ]
        },
        {
            "id": "task847-f2c507d4a75649e58b0218852a4f0339",
            "input": "To ascertain the prevalence of psychiatric symptoms and substance use disorders among adolescents with a lifetime history of foster care placement, using data from a nationally representative sample of U.S. adolescents.', 'We studied adolescents aged 12-17 years in the public use file of the 2000 National Household on Drug Abuse (n = 19,430, including 464 adolescents with history of foster care placement). Psychiatric symptoms and substance use disorders were ascertained through direct interviewing of adolescents. Logistic regression analyses were used to estimate the odds of past-year psychiatric symptoms and substance use disorders among adolescents involved with foster care, as compared to those without a lifetime history of foster care placement (comparison group).', 'Adolescents involved with foster care had more past-year psychiatric symptoms, and especially more conduct symptoms, and past-year substance use disorders than those never placed in foster care. Adolescents involved with foster care were about four times more likely to have attempted suicide in the preceding 12 months (adjusted odds ratio [AOR] 3.95; 95% confidence interval [CI] 2.78, 5.61), and about five times more likely to receive a drug dependence diagnosis in the same period (AOR 4.81; 95% CI 3.22, 7.18).",
            "output": [
                "Do psychiatric symptoms and substance use disorders in a nationally representative sample of American adolescents involved with foster care?"
            ]
        },
        {
            "id": "task847-7aee43fef84546f698cf83f568300ab1",
            "input": "Diagnosis of partial anomalous pulmonary venous return is usually suspected by echocardiography and often confirmed by cardiac catheterization. Magnetic resonance imaging is a powerful non-invasive diagnostic tool that can give accurate insight on systemic and pulmonary veins, cardiac anatomy and physiopathology.', 'To test the diagnostic accuracy of magnetic resonance in patient with suspected partial anomalous pulmonary venous return.', 'Twenty consecutive patients (10 male, mean age: 27+/-20 years) with suspected partial anomalous pulmonary venous return underwent a magnetic resonance study comprehensive of Gadolinium-enhanced three-dimensional magnetic resonance angiography and phase-velocity-contrast in order to evaluate pulmonary and systemic venous anatomy and QP/QS. In 14 of them a cardiac catheterization was also performed. Anatomy findings and QP/QS result of both exams were compared. Sixteen patients underwent surgical correction. In the other four patients with QP/QS<1.5, surgical correction was not indicated according to the literature (1). Among patients who had both magnetic resonance and cardiac catheterization (14 patients) anatomical findings were concordant in 12 of them. In all operated patients, surgical findings were concordant with MRI report. There was a good correlation between magnetic resonance and cardiac catheterization QP/QS evaluation (mean value 2.23 and 2.4, respectively).",
            "output": [
                "Is magnetic resonance imaging the diagnostic tool of choice in the preoperative evaluation of patients with partial anomalous pulmonary venous return?"
            ]
        },
        {
            "id": "task847-e98701a8c0bb4db6b94c68ea7b200228",
            "input": "The optimal treatment of acute cholecystitis is urgent laparoscopic cholecystectomy. Most reports suggest that a delay of 72 or 96 h from onset of symptoms leads to a higher conversion rate. This study assessed the conversion rate in relation to the timing of urgent laparoscopic cholecystectomy for acute cholecystitis.', 'During a 12 month period, 112 patients received laparoscopic cholecystectomy for acute cholecystitis at a tertiary care university hospital in central Taiwan. Data were collected prospectively.', 'The overall conversion rate was 3.6% (4/112). Of 62 procedures performed within 72 h from onset of symptoms, 2 were converted, as compared with 2 of 50 procedures after 72 h. Of 76 procedures performed within 96 h from onset of symptoms, 3 were converted, as compared with 1 of 36 procedures after 96 h. There were no mortalities or common bile duct injuries.",
            "output": [
                "Does urgent laparoscopic cholecystectomy in the management of acute cholecystitis : timing influence conversion rate?"
            ]
        },
        {
            "id": "task847-0d812f25acb24bed8bab45ca30a60364",
            "input": "Spinal reflex excitability study in sensory-motor incomplete spinal cord-injured (SCI) and spinal intact subjects.', 'To investigate the effects of plantar cutaneous afferent excitation on the soleus H-reflex and flexion reflex in both subject groups while seated.', 'Rehabilitation Institute of Chicago and City University of New York, USA.', 'The flexion reflex in SCI subjects was elicited by non-nociceptive stimulation of the sural nerve. In normal subjects, it was also elicited via innocuous medial arch foot stimulation. In both cases, reflex responses were recorded from the ipsilateral tibialis anterior muscle. Soleus H-reflexes were elicited and recorded via conventional methods. Both reflexes were conditioned by plantar cutaneous afferent stimulation at conditioning test intervals ranging from 3 to 90 ms.', 'Excitation of plantar cutaneous afferents resulted in facilitation of the soleus H-reflex and late flexion reflex in SCI subjects. In normal subjects, the soleus H-reflex was depressed while the late flexion reflex was absent. The early flexion reflex was irregularly observed in SCI patients, while in normal subjects a bimodal reflex modulation pattern was observed.",
            "output": [
                "Does plantar cutaneous input modulate differently spinal reflexes in subjects with intact and injured spinal cord?"
            ]
        },
        {
            "id": "task847-e738d62fe2904028ac2279482b6764ec",
            "input": "In light of the antinociceptive activity of the short-chain neurotoxin, cobrotoxin, and other acetylcholine antagonists, the antinociceptive activity and mechanisms of cobratoxin (CTX), a long-chain postsynaptic alpha-neurotoxin, was investigated in rodent pain models.', 'CTX was administered intraperitoneally (30, 45, 68 microg/kg), intra-cerebral ventricularly (4.5 microg/kg) or microinjected into periaqueductal gray (PAG; 4.5 microg/kg). The antinociceptive action was tested using the hot-plate and acetic acid writhing tests in mice and rats. The involvement of the cholinergic system and opioid system in CTX-induced analgesia was examined by pretreatment of animals with atropine (0.5 mg/kg, im; or 10 mg/kg, ip) or naloxone (1 and 5 mg/kg, ip). The effect of CTX on motor activity was tested using the Animex test.', 'CTX exhibited a dose-dependent analgesic action in mice as determined by both the hot-plate and acetic acid writhing tests. The peak effect of analgesia was seen 3 h after administration. In the mouse acetic acid writhing test, the intra-cerebral ventricular administration of CTX at 4.5 microg/kg (1/12th of a systemic dose) produced marked analgesic effects. Microinjection of CTX (4.5 microg/kg) into the PAG region did not elicit an analgesic action in rats in the hot-plate test. Atropine at 0.5 mg/kg (im) and naloxone at 1 and 5 mg/kg (ip) both failed to block the analgesic effects of CTX, but atropine at 10 mg/kg (ip) did antagonize the analgesia mediated by CTX in the mouse acetic acid writhing test. Acetylsalicylic acid (300 mg/kg) did not enhance the analgesic effects of CTX. At the highest effective dose of 68 microg/kg the neurotoxin did not change the spontaneous mobility of mice.",
            "output": [
                "Does a long-form alpha-neurotoxin from cobra venom produce potent opioid-independent analgesia?"
            ]
        },
        {
            "id": "task847-68e64ba780ee40b2872156556c72b51d",
            "input": "P2X1 receptors play an important role in platelet function as they can induce shape change, granule centralization and are also involved in thrombus formation. As platelets have no nuclei, the level of P2X1 expression depends on transcriptional regulation in megakaryocytes, the platelet precursor cell. Since nothing is known about the molecular mechanisms regulating megakaryocytic P2X1 expression, this study aimed to identify and functionally characterize the P2X1 core promoter utilized in the human megakaryoblastic cell line MEG-01.', 'In order to identify cis-acting elements involved in the transcriptional regulation of P2X1 expression, the ability of 4.7 kb P2X1 upstream sequence to drive luciferase reporter gene expression was tested. Low promoter activity was detected in proliferating MEG-01 cells. This activity increased 20-fold after phorbol-12-myristate-13-acetate (PMA) induced differentiation. A transcription start site was detected 365 bp upstream of the start codon by primer extension. Deletion analysis of reporter constructs indicated a core promoter located within the region -68 to +149 bp that contained two Sp1 sites (named Sp1a and Sp1b) and an NF-1 site. Individual mutations of Sp1b or NF-1 binding sites severely reduced promoter activity whereas triple mutation of Sp1a, Sp1b and NF-1 sites completely abolished promoter activity in both untreated and PMA treated cells. Sp1/3 and NF-1 proteins were shown to bind their respective sites by EMSA and interaction of Sp1/3, NF-1 and TFIIB with the endogenous P2X1 core promoter in MEG-01 cells was demonstrated by chromatin immunoprecipitation. Alignment of P2X1 genes from human, chimp, rat, mouse and dog revealed consensus Sp1a, Sp1b and NF-1 binding sites in equivalent positions thereby demonstrating evolutionary conservation of these functionally important sites.",
            "output": [
                "Do sp1/3 and NF-1 mediate basal transcription of the human P2X1 gene in megakaryoblastic MEG-01 cells?"
            ]
        },
        {
            "id": "task847-b204ecbd782d4fee83a74d6b0476c1e5",
            "input": "Smoking is known to cause chronic inflammatory changes in the bronchi and to contribute to airway hyper-reactivity, such as in bronchial asthma. To study the effect of smoking on the endothelin system in rat airways, bronchial segments were exposed to DMSO-soluble smoking particles (DSP) from cigarette smoke, to nicotine and to DMSO, respectively.', 'Isolated rat bronchial segments were cultured for 24 hours in the presence or absence of DSP, nicotine or DMSO alone. Contractile responses to sarafotoxin 6c (a selective agonist for ETB receptors) and endothelin-1 (an ETA and ETB receptor agonist) were studied by use of a sensitive myograph. Before ET-1 was introduced, the ETB receptors were desensitized by use of S6c. The remaining contractility observed was considered to be the result of selective activation of the ETA receptors. ETA and ETB receptor mRNA expression was analyzed using real-time quantitative PCR. The location and concentration of ETA and ETB receptors were studied by means of immunohistochemistry together with confocal microscopy after overnight incubation with selective antibodies.', 'After being cultured together with DSP for 24 hours the bronchial segments showed an increased contractility mediated by ETA and ETB receptors, whereas culturing them together with nicotine did not affect their contractility. The up-regulation of their contractility was blunted by cycloheximide treatment, a translational inhibitor. No significant change in the expression of ETA and ETB receptor mRNA through exposure to DMSO or to nicotine exposure alone occurred, although immunohistochemistry revealed a clear increase in ETA and ETB receptors in the smooth muscle after incubation in the presence of DSP. Taken as a whole, this is seen as the presence of a translation mechanism.",
            "output": [
                "Do smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi?"
            ]
        },
        {
            "id": "task847-5e16fcb3e05a453b910123f74eab85fe",
            "input": "Nitrogen-containing bisphosphonates (N-BPs) have been designed to inhibit osteoclast-mediated bone resorption. However, it is now accepted that part of their anti-tumor activities is related to interference with the mevalonate pathway.', 'We investigated the effects of zoledronic acid (ZOL), on cell proliferation and protein isoprenylation in two tumoral (LnCAP, PC-3,), and one normal established (PNT1-A) prostatic cell line. To assess if inhibition of geranyl-geranylation by ZOL impairs the biological activity of RhoA GTPase, we studied the LPA-induced formation of stress fibers. The inhibitory effect of ZOL on geranyl geranyl transferase I was checked biochemically. Activity of ZOL on cholesterol biosynthesis was determined by measuring the incorporation of 14C mevalonate in cholesterol.', 'ZOL induced dose-dependent inhibition of proliferation of all the three cell lines although it appeared more efficient on the untransformed PNT1A. Whatever the cell line, 20 microM ZOL-induced inhibition was reversed by geranyl-geraniol (GGOH) but neither by farnesol nor mevalonate. After 48 hours treatment of cells with 20 microM ZOL, geranyl-geranylation of Rap1A was abolished whereas farnesylation of HDJ-2 was unaffected. Inhibition of Rap1A geranyl-geranylation by ZOL was rescued by GGOH and not by FOH. Indeed, as observed with treatment by a geranyl-geranyl transferase inhibitor, treatment of PNT1-A cells with 20 microM ZOL prevented the LPA-induced formation of stress fibers. We checked that in vitro ZOL did not inhibit geranyl-geranyl-transferase I. ZOL strongly inhibited cholesterol biosynthesis up to 24 hours but at 48 hours 90% of this biosynthesis was rescued.",
            "output": [
                "Does zoledronic acid treatment impair protein geranyl-geranylation for biological effects in prostatic cells?"
            ]
        },
        {
            "id": "task847-13d2629d6ebf418fa053f6fdae696596",
            "input": "Lymphocyte alterations have been associated with an increased prevalence of acute respiratory infections in COPD patients. AM3 is an oral immunomodulator that normalizes the defective functions of peripheral blood natural killer and phagocytic cells in COPD patients and improves their health-related quality of life.', 'To characterize putative systemic abnormalities of the T-cell compartment in COPD patients, and to investigate whether AM3 can restore such abnormalities.', 'The study was a randomized, prospective, double-blind, placebo-controlled trial in a cohort of COPD patients. The results were also compared to those of nonsmoker and ex-smoker healthy control subjects.', 'Outpatient departments of four hospitals.', 'Seventy COPD patients were randomized to receive either AM3 or a placebo orally for 90 consecutive days. Populations of 36 healthy nonsmokers and 36 healthy ex-smokers were used as control subjects.', 'Peripheral blood mononuclear cell (PBMC) proliferation and production of interleukin (IL)-2, IL-4, IL-12p40, tumor necrosis factor-alpha, and interferon (IFN)-gamma proteins in response to the T-cell polyclonal mitogens were assessed at baseline and at the end of treatment.', 'The proliferative response was significantly decreased in COPD patients. Decreased production of IFN-gamma was the only defect in the profiles of the cytokine measures, and was selectively observed in COPD patients, but not in nonsmoker and ex-smoker healthy control subjects. Treatment with AM3 significantly restored the PBMC proliferative response to polyclonal mitogens and significantly promoted stimulated IFN-gamma production in these patients. The normalization of these proliferative responses was not related to significant variations in the numbers of peripheral blood monocytes, CD3+, CD4+, CD8+ cells or of any major na\u00efve/memory/activated T-cell subset. The increased IFN-gamma production in the AM3 study arm was associated with an increase in the mean of number of IFN-gamma molecules produced per CD8+ T cells.",
            "output": [
                "Does treatment with AM3 restore defective T-cell function in COPD patients?"
            ]
        },
        {
            "id": "task847-aaf29152a28d474f81a62d2904753763",
            "input": "This study extends our previously reported observations that various immunological factors are associated with the occurrence of histologically proven recurrent hepatitis C. The two specific issues investigated were to confirm the associations of MHC alleles and donor/recipient mismatch with the occurrence of recurrent hepatitis C in an independent cohort of newly transplanted patients and to look for immunologic and nonimmunologic variables affecting the severity of the recurrent disease.', 'Two separate cohorts of consecutive patients were studied: a look-back cohort (LC) of 120 patients and a cohort for studying the disease progression (CSDP) of 190 patients. Protocol liver biopsies were obtained at least 1, 3, 5, 7, and 10 years after liver transplantation (LT).', 'A fully mismatched donor/recipient pair at the DRB1 locus was confirmed to be associated with both the recurrence of histologic hepatitis in the LC (59% vs 23%, P = .0002) and its progression beyond stage 3 in the CSPD (71.4% vs 39.3%, P = .0003). Relevant immunologic and nonimmunologic variables were included into a multivariate Cox proportional model and three variables, namely, donor age, full HLA-DRB1 donor-recipient mismatch, and HLA B14, resulted in independent risk factors for the development of severe fibrosis.",
            "output": [
                "Does hLA-DRB1 donor-recipient mismatch affect the outcome of hepatitis C disease recurrence after liver transplantation?"
            ]
        },
        {
            "id": "task847-47896e4d782d452689a2b34facec9f2f",
            "input": "We examined the influence of head-tilting on stabilometry, which is similar to positional nystagmus in a sitting position.', \"The subjects were 35 healthy individuals and 11 patients with unilateral vestibular disorder. We compared parameters measured in an upright position and those with left head-tilt or right head-tilt. We used Wilcoxon's signed ranks test for statistical analysis.\", 'In the group of healthy adults, the Enveloped area with left head-tilt and right head-tilt increased significantly compared to that in the upright position (P=0.0111). The parameters that decreased significantly were Locus length per unit area (P=0.0007). The center of gravity on the Y-axis shifted backward significantly (P<0.0001). In the group of unilateral vestibular disorder, there were no parameters that showed significant difference",
            "output": [
                "Does comparison between stabilometry with and without head tilt in a roll plane?"
            ]
        },
        {
            "id": "task847-1151c0c03ede48849fe8af9b5ef8ff83",
            "input": "To examine in a cross sectional study the influence of femoral torsion (FT) and passive hip external rotation (PER) on turnout (TO). Starting age, years of classical ballet training, and current and past dance training intensity were assessed to determine their influence on FT, PER, and TO in pre-professional female dancers.', 'Sixty four dancers (mean (SD) age 18.16 (1.80) years) were recruited from four different dance training programmes. They completed a dance history questionnaire. FT was measured using a clinical method. PER was measured with the subjects prone, and TO was measured with the subjects standing.', 'Mean TO was 136 degrees, mean unilateral PER was 49.4 degrees, and mean FT was 18.4 degrees. A positive correlation was observed between PER combined (PERC) and TO (r = 0.443, p < 0.001). A negative association was found between FT combined (FTC) and PERC (r = -0.402, p = 0.001). No association was found between starting age or years of classical ballet training and FTC, PERC, or TO. Dancers who trained for six hours a week or more during the 11-14 year age range had less FT than those who trained less (mean difference 6 degrees, 95% confidence interval 1.4 to 10.3). Students currently training for longer had higher levels of TO (p < 0.001) but comparable PERC and FTC.",
            "output": [
                "Is dance training intensity at 11-14 years associated with femoral torsion in classical ballet dancers?"
            ]
        },
        {
            "id": "task847-e884ce60e4ff42cd99159c53990f6774",
            "input": "Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. Due to very poor 5-year-survival new therapeutic approaches are mandatory. Most HCCs express insulin-like growth factors and their receptors (IGF-R). As IGF-1R-mediated signaling promotes survival, oncogenic transformation and tumor growth and spread, it represents a potential target for innovative treatment strategies of HCC. Here we studied the antineoplastic effects of inhibiting IGF-1R signaling in HCC cells by the novel IGF-1R tyrosine kinase inhibitor NVP-AEW541.', 'NVP-AEW541 induced a time- and dose-dependent growth inhibition in the human hepatoblastoma and hepatocellular carcinoma cell lines SK-Hep-1, Hep-3B, Hep-G2 and Huh-7. Measurement of LDH-release showed that the antineoplastic effect of NVP-AEW541 was not due to cytotoxicity. Instead NVP-AEW541 induced apoptosis as evidenced by both caspase-3 and -8 activation as well as by apoptosis-specific morphological and mitochondrial changes. In addition, nuclear degradation was monitored by DNA-laddering. NVP-AEW541-treatment suppressed the expression of the antiapoptotic proteins Bcl-2 and survivin, while the expression of the proapoptotic protein BAX was stimulated in a dose-dependent manner. Moreover, NVP-AEW541 arrested the cell cycle at the G1/S checkpoint. When NVP-AEW541 was combined with cytotoxic chemotherapy or with a specific epidermal growth factor receptor antibody additive antiproliferative effects were observed.",
            "output": [
                "Does blockade of IGF-1 receptor tyrosine kinase have antineoplastic effects in hepatocellular carcinoma cells?"
            ]
        },
        {
            "id": "task847-445f79e78f504a19b2838836f59dbecc",
            "input": "We tested the hypothesis that the negative functional effects of cyclic GMP would be attenuated by cyclic AMP and this interaction would be reduced in pacing-induced failure of hypertrophic hearts.', '8-Bromo-cGMP (2 microg/kg/min) was infused into a coronary artery in eight control, eight ventricular hypertrophy (HYP), and eight hypertrophic failure (HYP-FAIL) dogs. Then isoproterenol (0.1 microg/kg/min) was infused, followed by 8 Br-cGMP. Regional myocardial work (force*shortening/min), and O(2) consumption (VO(2)) (coronary blood flow*O(2) extraction) were measured. Cyclic GMP levels were determined by radioimmunoassay.', '8-Br-cGMP significantly decreased regional work from 3812 +/- 839 g*mm/min by 17% and VO(2) by 29% in control, but not in HYP (1073 +/- 182 by -10%, VO(2) by -16%) or HYP-FAIL (495 +/- 145 by -9%, VO(2) by 0%). Isoproterenol increased work by 43% and VO(2) by 48% in controls and in HYP (work by 54%, VO(2) by 39%), but not in HYP-FAIL (work by -28%, VO(2) by -5%). Subsequently, 8-Br-cGMP had no effect on work or VO(2) in control (-2%, -13%), HYP (-12%, -30%), or HYP-FAIL (+13%, +14%). Cyclic AMP levels were elevated by isoproterenol in control (381 +/- 115 versus 553 +/- 119 pmol/g) and HYP (313 +/- 55 versus 486 +/- 227), but not in HYP-FAIL (300 +/- 60 versus 284 +/- 126). After isoproterenol, 8-Br-cGMP further elevated cyclic AMP in control (687 +/- 122), but not in HYP or HYP-FAIL.",
            "output": [
                "Does heart failure reduce both the effects and interaction between cyclic GMP and cyclic AMP?"
            ]
        },
        {
            "id": "task847-8a584fd76bc245e9b6e85d2d6a1fd384",
            "input": "To apply clarithromycin as an immunomodulatory treatment in experimental infection caused by pan-resistant Klebsiella pneumoniae.', 'Acute pyelonephritis was induced in 80 rabbits after inoculation of the test isolate in the renal pelvis. Rabbits were divided into eight groups, with 10 animals in each group. In groups A-D, therapy was administered simultaneously with bacterial challenge as follows: A, controls; B, intravenous clarithromycin; C, amikacin; and D, both agents. In groups E-H, therapy was administered 24 h after bacterial challenge as follows: E, controls; F, intravenous clarithromycin; G, amikacin; and H, both agents. Blood was sampled for estimation of tumour necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA); monocytes were isolated for determination of intracellular activity of caspase-3 and ex vivo TNF-alpha secretion. Four days after bacterial challenge, animals were sacrificed for quantitative cultures and biopsies of organs.', 'Serum TNF-alpha at 48 h was lower in groups B, C and D compared with group A. Activity of caspase-3 of monocytes was lower at 48 h in group D compared with group A. Bacterial loads of liver and spleen were decreased in group D compared with those of group A. The numbers of inflammatory cells of spleen of group B were lower compared with those of group A; those of kidney and mesenteric lymph nodes of group D were lower than those of group A. Serum MDA of group H was lower than that of group E and serum TNF-alpha of group F was lower compared with that of group E. TNF-alpha of monocyte supernatants and activity of caspase-3 of monocytes of group F were lower than those of group E. Bacterial tissue loads did not differ among groups E, F, G and H. The numbers of inflammatory cells of liver of groups F and H were lower compared with those of group E; those of kidney of groups F, G and H were lower compared with those of group E.",
            "output": [
                "Is clarithromycin an effective immunomodulator in experimental pyelonephritis caused by pan-resistant Klebsiella pneumoniae?"
            ]
        },
        {
            "id": "task847-7d4fe83de99c4b6d938e39987e6b8dbe",
            "input": "Therapeutic ultrasound is an effective deep heating modality commonly applied alone or after cooling or heating of the treatment area. The purpose of this study was to examine the tissue temperature rise in the human triceps surae muscle group after ultrasound with prior heating via a silicate gel hot pack.', 'This study was designed as a 2 x 2 x 3 factorial with repeated measures on two factors (depth and time). Independent variables were temperature of pack (hot and room temperature), depth of measurement (1 cm and 3 cm), and time (beginning, after pack application, and after ultrasound). The dependent variable was tissue temperature. Subjects were assigned to one of two treatment groups: ultrasound preceded by a 15-minute hot pack treatment or ultrasound preceded by a 15-minute application with a silicate gel pack at room temperature. Measurements were taken while subjects were treated in a university training room.', 'Twenty-one uninjured male and female college student volunteers were randomly assigned to one of the two pack groups.', 'The hot packs were stored in 75 degrees C water. A 1-MHz ultrasound treatment was administered for 10 minutes at an intensity of 1.5 W/cm(2). Tissue temperature was measured every 30 seconds using 23-gauge hypodermic microprobes interfaced with a telethermometer and inserted 1 and 3 cm below the surface of anesthetized triceps surae muscle.', 'At both tissue depths, there was a 0.8 degrees C greater increase in tissue temperature with hot packs and ultrasound. At 1 cm, ultrasound increased temperature 3.5 degrees C after a 0.5 degrees C rise during the room temperature-pack application, but only 0.6 degrees C after a 3.8 degrees C increase during hot-pack application. At 3 cm, ultrasound increased temperature 3.85 degrees C following a slight (-0.26 degrees C) decrease during the room temperature-pack application and 3.68 degrees C after a 0.74 degrees C increase during hot-pack application.",
            "output": [
                "Do hot-Pack and 1-MHz Ultrasound Treatments Have an Additive Effect on Muscle Temperature Increase?"
            ]
        },
        {
            "id": "task847-0dea0029a5354715b34893c049f13af6",
            "input": "To observe the effect of recombinant human epithelial growth factor (rhEGF) in promoting the healing of cervical erosion.', 'Forty-eight patients with cervical erosion were treated with rhEGF and 30 with 500 kHz high-frequency electromagnetic wave, and the effects of the therapies were compared in terms of healing of the cervical wound, healing time, volume of vaginal discharge and bleeding and the lasting time.', 'In comparison with radiofrequency therapy, the healing of the lesion took significantly shorter time with rhEGF therapy, which also resulted in less vaginal discharge that lasted for shorter time without causing vaginal bleeding.",
            "output": [
                "Does [ Recombinant human epithelial growth factor accelerate healing of cervical erosion ]?"
            ]
        },
        {
            "id": "task847-916b8f744a104522bebc4a73b894af9a",
            "input": "Atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. Scratching due to pruritus is an important mechanism in the exacerbation of AD but is difficult to document in the home environment.', 'To evaluate whether nocturnal wrist activities, defined as average acceleration in the early hours of sleep, were correlated with components of the SCORing Atopic Dermatitis (SCORAD) index and various AD-associated chemokine markers.', 'Patients with AD aged under 18 years were recruited and the severity of eczema was assessed with the SCORAD index. Concentrations of plasma AD-associated chemokines [cutaneous T-cell attracting cytokine (CTACK); macrophage-derived chemokine (MDC); thymus and activation regulated chemokine (TARC)], interleukin (IL)-18, serum total IgE, and eosinophil counts were measured in these patients. Healthy children with noninflammatory and nonitchy skin conditions as well as healthy children of staff volunteers were recruited as controls. All children were instructed to wear the DigiTrac monitor on their dominant wrist before sleeping. The monitor was programmed to record limb motion between 22.00 and 08.00 h the following morning.', 'Twenty-four Chinese children with AD (mean +/- SD age 12.6 +/- 3.7 years) and 15 normal children (mean +/- SD age 11.9 +/- 3.4 years) were recruited. The median (interquartile range) SCORAD was 54.8 (32.8-70.2). Plasma concentrations in pg mL(-1) of CTACK, MDC, TARC and IL-18 in the patients were 105 (92-172), 1648 (973-4214), 258 (100-850) and 415 (304-539), respectively. When compared with controls, most wrist activities occurred at frequencies between 1 and 3 Hz. These activities were most consistent over the first 3 h of sleeping and correlated significantly with disease severity, extent, intensity, and AD-associated chemokine markers CTACK, MDC and TARC. However, there was no significant correlation between wrist activities and the subjective symptom of pruritus or sleep loss.",
            "output": [
                "Are nocturnal wrist movements correlated with objective clinical scores and plasma chemokine levels in children with atopic dermatitis?"
            ]
        },
        {
            "id": "task847-a3fc5e0601d64d98a317963ce9d1af84",
            "input": "A predominance of type 2 helper T cells (Th2) in the bronchoalveolar space and peripheral blood is a well-accepted feature of bronchial asthma. However, the relationship between peripheral blood Th2 cells and asthma severity has not been thoroughly investigated.', 'As Th1 cells predominantly express the chemokine receptor CXCR3 and Th2 cells express CCR4, we assessed the distribution of peripheral blood CXCR3+ and CCR4+ lymphocytes using flow cytometry in 186 patients with asthma and 75 normal subjects.', \"The proportion of CXCR3+/CD45RO+ cells in CD4+ T cells increased as the severity of asthma increased. The percentage of CCR4+/CD45RO+ cells in CD4+ T cells were elevated in mild to severe asthma patients compared with controls. However, there was no significant difference in CCR4+/CD45RO+ cells between the mild to severe asthma patients. There was no relationship between the patient's age and the numbers of CXCR3+ or CCR4+ T cells. The percentage of CCR4+ cells in CD45RO+/CD4+ T cells correlated with the levels of total serum IgE (r = 0.630, P < 0.0001).",
            "output": [
                "Is asthma severity associated with an increase in both blood CXCR3+ and CCR4+ T cells?"
            ]
        },
        {
            "id": "task847-c8ad35fe8b5b456b8d607952fecd8eb7",
            "input": "The aim of the current study was to test the impact of dentin powder on the antimicrobial efficacy of bioactive glass S53P4 (BAG).', 'BAG was suspended (preincubated) in saline at 37 degrees C for different time periods with or without human dentin powder, hydroxylapatite, or decalcified dentin. Subsequently, Enterococcus faecalis ATCC 29212 cells were added to these suspensions and bacterial recovery measured with and without the use of gentle sonication. Furthermore, survival of bacteria in test and control suspensions was assessed over time. Supernatants of suspensions were analyzed for their element contents using atomic absorption spectrophotometry. The effects of pH, silica, and osmolarity on E faecalis viability were assessed using specifically prepared solutions.', 'BAG preincubated with dentin powder caused a significant (P < .05) decrease in viability compared to pure BAG suspensions. This was not based on adherence of bacteria to solid particles or agglutination of the cells, because sonication did not increase bacterial yields. Hydroxylapatite and decalcified dentin did not increase BAG killing efficacy. The additive effect of BAG + dentin powder was dose dependent, occurred only with solids in suspension, and increased with suspension time. An augmented dissolution of glass components, especially silicon, was measured in BAG + dentin powder compared to pure BAG suspensions or counterparts containing hydroxylapatite or decalcified dentin. High osmolarity per se did not affect E faecalis viability, whereas high pH and silica levels did.",
            "output": [
                "Does dentin enhance the effectiveness of bioactive glass S53P4 against a strain of Enterococcus faecalis?"
            ]
        },
        {
            "id": "task847-3f4dab8d0eaa4452ad54acb71a5ac62b",
            "input": "To determine the effect of introducing a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer on the percentage of emergency department (ED) patients evaluated for pulmonary embolism (PE), the use of associated laboratory testing, pulmonary vascular imaging, and the diagnoses of PE.', 'Patients evaluated for PE during three 120-day periods were enrolled: immediately before (period 1), immediately after (period 2), and one year after the introduction of a rapid ELISA D-dimer in the hospital. The frequency of ED patients evaluated for PE with any test, with D-dimer testing, and with pulmonary vascular imaging and the frequency of PE diagnosis during each time period were determined.', 'The percentage of patients evaluated for PE nearly doubled; from 1.36% (328/24,101) in period 1 to 2.58% (654/25,318) in period 2 and 2.42% (583/24,093) in period 3. The percentage of patients who underwent D-dimer testing increased more than fourfold; from 0.39% (93/24,101) in period 1 to 1.83% (464/25,318) in period 2 and 1.77% (427/24,093) in period 3. The percentage of patients who underwent pulmonary vascular imaging increased from 1.02% (247/24,101) in period 1 to 1.36% (344/25,318) in period 2 and to 1.39% (334/24,093) in period 3. There was no difference in the percentage of patients diagnosed as having PE in period 1 (0.20% [47/24,101]), period 2 (0.27% [69/25,318]), and period 3 (0.24% [58/24,093]).",
            "output": [
                "Does a highly sensitive ELISA D-dimer increase testing but not diagnosis of pulmonary embolism?"
            ]
        },
        {
            "id": "task847-6673d2dd56254aa395065c38b47dc313",
            "input": "Epithelial lining fluid plays a critical role in protecting the lung from oxidative stress, in which the oxidised status may change by ageing, smoking history, and pulmonary emphysema.', 'Bronchoalveolar lavage (BAL) was performed on 109 young and older subjects with various smoking histories. The protein carbonyls, total and oxidised glutathione were examined in BAL fluid.', 'By Western blot analysis, the major carbonylated protein in the BAL fluid was sized at 68 kDa, corresponding to albumin. The amount of carbonylated albumin per mg total albumin in BAL fluid was four times higher in older current smokers and three times higher in older former smokers than in age matched non-smokers (p<0.0001, p=0.0003, respectively), but not in young smokers. Total glutathione in BAL fluid was significantly increased both in young (p=0.006) and older current smokers (p=0.0003) compared with age matched non-smokers. In contrast, the ratio of oxidised to total glutathione was significantly raised (72%) only in older current smokers compared with the other groups. There was no significant difference in these parameters between older smokers with and without mild emphysema.",
            "output": [
                "Does long term smoking with age build up excessive oxidative stress in bronchoalveolar lavage fluid?"
            ]
        },
        {
            "id": "task847-c04265ce5ac243489eb4a61ebe7d0a8c",
            "input": "Side effects of mitotane (o,p'-DDD) have suggested estrogenic effects.\", \"The objective of the study was to explore o,p'-DDD potential estrogenic effect on SHBG and corticosteroid-binding globulin (CBG).\", 'Human hepatoma cell lines (HepG2), lacking estrogen receptor (ER)-alpha, and Hep89, stably transfected by ERalpha, were used.', 'The study was conducted at an academic research laboratory and medical center.', 'The study included 10 male patients with recurrent adrenal carcinoma, receiving mitotane (4-6.5 g daily) for more than 6 months.', 'The main outcome measures were SHBG/CBG mRNA levels measured by real-time PCR, culture medium SHBG/CBG concentrations measured by specific immunoassays, and transient transfection experiments with human SHBG proximal promoter reporter constructs.', \"Increased serum SHBG and CBG concentrations, which exceeded normal male limits, were observed in most mitotane-treated patients. In the HepG2 cell line, 17beta-estradiol (E2) or o,p'-DDD treatment had no effect on mRNA or SHBG/CBG concentrations. In contrast, in the Hep89 cell line, E2 increased concentrations of SHBG (r = 0.44, P < 0.0001) and CBG (r = 0.585, P < 0.0001) secreted into culture media in a dose-dependent manner. o,p'-DDD significantly increased SHBG (150% vs. control, P < 0.05) and CBG (184% vs. control, P < 0.05) production by Hep89 cells, at a concentration of 2 x 10(-5) m. Transient transfection experiments in Hep89 cells showed that E2 or o,p'-DDD treatment did not increase the transcriptional activity of the minimal proximal promoter of human SHBG gene.",
            "output": [
                "Does mitotane have an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans?"
            ]
        },
        {
            "id": "task847-31987115875e40b5a1a44c71d664ffd7",
            "input": "Systemic hypertension is one of the main risk factors for atherothrombosis. Tissue factor (TF) is found in the adventitia of blood vessels and in the lipid core of atherosclerotic plaques, and is specifically expressed on monocyte or macrophage cell membrane surfaces. TF plays a pivotal role in blood clotting physiology and is involved in pro-inflammatory action and atherosclerotic plaque destabilization.', 'In this study we investigated whether there is any relationship between TF messenger RNA expression and activity in blood monocytes isolated from hypertensive patients with clinical signs of atherosclerosis, uncomplicated hypertensive individuals and normotensive control subjects.', 'Eighty subjects (41 men and 39 women, mean age 41 +/- 12 years) with untreated essential hypertension and 41 control subjects matched for sex and age were enrolled in the study. Patients were classified according to whether they had a normal (</= 1 mm, 41 patients) or abnormal (> 1 mm, 39 patients) intima-media thickness (IMT).', 'TF mRNA expression and activity in hypertensive individuals with no carotid atherosclerosis were no different from control subjects in unstimulated and stimulated monocytes. Abnormal IMT patients showed a higher TF mRNA expression compared with normal IMT hypertensive subjects (P < 0.001).",
            "output": [
                "Are tissue factor expression and activity increased in peripheral monocytes isolated from uncomplicated hypertensive patients?"
            ]
        },
        {
            "id": "task847-26a48f6a13464772b55ac7308d583be5",
            "input": "The aim of the present study was to determine whether inhibition of reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] oxidase and of various superoxide generating systems could affect the collagen production, the mRNA and protein expression of collagen types I and III in control and angiotensin II-treated cardiac fibroblasts.', \"Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency and incubated in serum-free Dulbecco's modified Eagle's medium for 24 h. The cells were then preincubated with(out) the tested inhibitors for 1 h and then further incubated with(out) angiotensin II (1 micromol/l) for 24 h. Collagen production was measured spectrophotometrically with picrosirius red as dye and with [3H]proline incorporation; collagen type I and III content by enzyme-linked immunosorbent assay and collagen type I and III mRNA expression by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). NAD(P)H-dependent superoxide anion production was assayed as superoxide dismutase-inhibitable cytochrome c reduction. Intracellular formation of reactive oxygen species was assessed with 2',7'-dichlorofluorescein diacetate as fluorescent probe.\", 'Angiotensin II stimulated the collagen production, the collagen I and III content and mRNA expression in cardiac fibroblasts, and apocynin, a membrane NAD(P)H oxidase inhibitor, abolished this induction. Rotenone, allopurinol, indomethacin, nordihydroguiaretic acid, ketoconazole and nitro-L-arginine (inhibitors of mitochondrial NAD(P)H oxidase, xanthine oxidase, cyclooxygenase, lipoxygenase, cytochrome P450 oxygenase and nitric oxide synthase, respectively) did not affect the angiotensin II-induced collagen production. Angiotensin II increased the NAD(P)H-dependent superoxide anion production and the intracellular generation of reactive oxygen species in cardiac fibroblasts, and apocynin abrogated this rise.",
            "output": [
                "Is angiotensin II-stimulated collagen production in cardiac fibroblasts mediated by reactive oxygen species?"
            ]
        },
        {
            "id": "task847-cfcb47bb2a8b4e9ea7df6907eca4b9e5",
            "input": "During sepsis, a two- to four-fold increase in circulating growth hormone (GH) is seen with 40-50% reductions in plasma insulin-like growth factor (IGF)-I. The suppressors of cytokine signaling (SOCS), inhibitors of cytokine, and growth factor signaling via the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway have been implicated in the development of hepatic GH resistance. In this study we examine the effects of sepsis on GH-induced IGF-I expression and potential mechanisms for GH resistance.', 'Prospective experimental study.', 'University research laboratory.', 'Male Sprague-Dawley rats.', 'Rats were randomized to laparotomy alone (control) or implantation of fecal agar pellets inoculated with Escherichia coli and Bacteroides fragilis (sepsis). GH was injected intravenously to assess hepatic IGF-I synthesis and GH signaling.', 'Plasma IGF-I was measured in both groups at baseline (4 hrs postoperatively) and then again at 12 hrs and 24 hrs after GH administration. Basal IGF-I levels were similar in both groups, but controls had a 35% increase in IGF-I at 12 hrs, whereas septic rats demonstrated reductions in circulating IGF-I at 12 and 24 hrs after GH. Hepatic expression of SOCS-1, -2, -3, and cytokine-inducible SH2-containing protein (CIS) were determined at 1, 4, 8, and 24 hrs in septic and control rats by Northern blot. SOCS-1, SOCS-3, and CIS messenger RNA in liver were increased from 4 to 8 hrs after the induction of sepsis (p < .05 for SOCS-1 and -3). Total GH receptor (GHR), JAK2, and STAT5 signaling proteins and the time course of STAT5 activation were also measured in liver after recombinant human GH administration by immunoblot and electrophoretic mobility shift analysis. Levels of total GHR, JAK2, and STAT5 were unaltered in liver from septic rats. However, phosphorylated STAT5 and STAT5 DNA binding were significantly reduced 30 mins after GH administration in liver from septic rats.",
            "output": [
                "Is hepatic growth hormone resistance during sepsis associated with increased suppressors of cytokine signaling expression and impaired growth hormone signaling?"
            ]
        },
        {
            "id": "task847-b88caa94e49c4411a11529f0dfcc41fe",
            "input": "Survival from acute coronary syndromes and major trauma has been shown to depend on timely access to definitive treatment. We sought to identify the significance of intensive care unit (ICU) admission delay (lead-time) on the outcome of critically-ill medical patients with other diagnoses.', 'From 1 January 1997 to 31 December 2003, a prospective cohort study was performed in critically-ill patients requiring mechanical ventilatory support (MV) and/or renal replacement therapy (RRT), admitted directly to the Northern Hospital ICU within 24 hours of arrival in the emergency department (ED). Patients were excluded if, a) they were admitted following surgery, major trauma or transfer from another hospital, or b) their duration of ICU stay was < 8 hours. Data collected included de-identified patient demographics, final diagnosis, APACHE II mortality risk (pm) and lead-time (i.e. difference between times of entrance to the ED and ICU.) The primary outcome measure was hospital discharge status.', 'Six hundred and nineteen consecutive ICU admissions from the ED met the inclusion criteria and required MV (n = 557) and/or RRT (n = 162.) Non-survivors were older (median age 73 vs. 54 yrs) and sicker (median pm 0.72 vs. 0.23) compared with survivors. Multivariate analysis using logistic regression identified lead-time as a significant predictor of mortality (RR = 1.06 per hour, 95% CI =1.01 - 1.10; p=0.015) in addition to age, diagnosis and illness severity.",
            "output": [
                "Is survival of critically ill medical patients time-critical?"
            ]
        },
        {
            "id": "task847-8e1f0233c8c84e189370a21df1146c97",
            "input": "In order to improve the survival of patients with a glioblastoma multiforme tumor (GBM), new therapeutic strategies must be developed. The use of a death inducing ligand such as TRAIL (TNF Related Apoptosis Inducing Ligand) seems a promising innovative therapy. The aim of this study was to quantify the expression of the death regulating receptors TRAIL-R1, TRAIL-R2 and TRAIL on primary GBM specimens and to correlate this expression with survival.', 'Expression of TRAIL and TRAIL-receptors was assessed by immunohistochemistry, both quantitatively (% of positive tumor cells) and semi-quantitatively (staining intensity) within both the perinecrotic and intermediate tumor zones of primary GBM specimens. RT-PCR of GBM tissue was performed to show expression of TRAIL receptor mRNA.', 'Immunohistochemistry showed a slight diffuse intracytoplasmic and a stronger membranous staining for TRAIL and TRAIL receptors in tumor cells. Semi-quantitative expression of TRAIL showed a significantly higher expression of TRAIL in the perinecrotic zone than in the intermediate zone of the tumor (P=0.0001). TRAIL-R2 expression was significantly higher expressed than TRAIL-R1 (P=0.005). The antigenic load of TRAIL-R2 was positively correlated with survival (P=0.02). Multivariate analysis of TRAIL-R1 within the study group (n=62) showed that age, gender, staining intensity, antigenic load, % of TRAIL-R1 expression, were not statistically correlated with survival however radiotherapy was significantly correlated (multivariate analysis: age: P=0.15; gender: P=0.64; staining intensity: P=0.17; antigenic load: P=0.056; % of TRAIL-R1 expression: P=0.058; radiotherapy: P=0.0001). Subgroup analysis of patients who had received radiotherapy (n=47) showed a significant association of % of TRAIL-R1 expression and the antigenic load of TRAIL-R1 with survival (multivariate analysis: P=0.036, respectively, P=0.023). Multivariate analysis of TRAIL-R2 staining intensity and antigenic load, within the study group (P=0.004, respectively, P=0.03) and the subgroup (P=0.002, respectively, P=0.004), showed a significant association with survival. RT-PCR analysis detected a negative relation between the amount of TRAIL-R1 mRNA and the WHO grade of astrocytic tumors (P=0.03).",
            "output": [
                "Is tRAIL-receptor expression an independent prognostic factor for survival in patients with a primary glioblastoma multiforme?"
            ]
        },
        {
            "id": "task847-dcce146e226b464599695986728b3a78",
            "input": "The purpose of this study was to investigate the impact of using a rewetting drop (RWD) containing surface active agents (OPTI-FREE RepleniSH; Alcon, Fort Worth, TX) on the clinical performance and protein deposition when using a continuous-wear (CW) silicone hydrogel (SH) contact lens.', 'Subjects wore lotrafilcon A SH lenses on a 30-day CW basis for two consecutive 1-month periods while inserting either 0.9% unpreserved unit-dose saline (control) or multidose OPTI-FREE RepleniSH (test RWD). Subjective comfort and symptoms were assessed after 2 and 4 weeks with each product. After 1 month of wear with each product, lenses were collected and analyzed in the laboratory for total protein, total lysozyme, and percentage of denatured lysozyme.', 'Symptoms of dryness and comfort varied across the day regardless of drop type (p < 0.001) with dryness being maximal on waking, least in the middle of the day, and increased towards the evening. The test RWD provided greater comfort on insertion (p = 0.02), better visual quality (p < 0.01), and less mucous discharge on waking (p = 0.02) than the control product. Lysozyme deposition was significantly reduced after the use of the test RWD as compared to saline (0.73 +/- 0.5 microg/lens vs. 1.14 +/- 0.7 microg/lens; p < 0.001) as was total protein deposition (1.17 +/- 0.7 microg/lens vs. 1.86 +/- 0.8 microg/lens; p < 0.001). Lysozyme denaturation was also reduced with the use of the test RWD compared with the control (76 +/- 10% vs. 85 +/- 7%; p < 0.01).",
            "output": [
                "Do rewetting drops containing surface active agents improve the clinical performance of silicone hydrogel contact lenses?"
            ]
        },
        {
            "id": "task847-ce70407f1b0049b9a9aa382e0be511d9",
            "input": "Patients sensitized to airborne fungi such as Alternaria alternata and Cladosporium herbarum often also show positive skin prick test results and specific serum IgE antibodies to a yeast, Pityrosporum ovale. We examined whether part of the IgE binding to these fungi is explained by cross-reacting mould and yeast allergens.', 'Serum samples from 36 patients with positive skin prick test to A. alternata or C. herbarum were analyzed for IgE antibodies to fungal extracts by ELISA and immunoblot analysis. Cross-reactivity between mould and yeast extracts was studied by ELISA and immunoblot inhibition assays. In further analysis, the mannan-containing glycoproteins were removed from the yeast extract by concanavalin A-Sepharose chromatography, and the IgE binding properties of the extracts were compared.', 'Serum IgE reactivity to P. ovale was found in 40% of the mould-sensitized patients. The IgE antibody binding to A. alternata and C. herbarum moulds was partially inhibited by the yeast P. ovale in ELISA and immunoblot inhibition assays. When the glycoproteins were removed from the extract, cross-reactivity was markedly reduced.",
            "output": [
                "Do cladosporium herbarum and Pityrosporum ovale allergen extracts share cross-reacting glycoproteins?"
            ]
        },
        {
            "id": "task847-7f25c84c75334b299bb9993d029432a9",
            "input": "Large-artery stiffness and arterial wave reflections have been identified as independent markers and prognosticators of cardiovascular risk. Mental stress is a novel risk factor for coronary artery disease and has been associated with left ventricular dysfunction, myocardial ischemia and infarction, and sudden cardiac death. The purpose of this study was to assess the effect of acute mental stress on aortic stiffness and wave reflections.', 'The effect of a mental arithmetic test was assessed in 19 healthy individuals using a randomized, sham-procedure-controlled, crossover design. Carotid-femoral pulse wave velocity and augmentation index were measured as indices of aortic stiffness and wave reflections, respectively.', 'Mental stress induced a sustained increase in central systolic and pulse pressure throughout the whole study (systolic: by 7.5 mm Hg, p < .05; pulse: by 5.7 mm Hg, p < .01). The increase in peripheral systolic and pulse pressure was not significant throughout the study, but only when their peak values were compared with baseline (systolic: by 6.2 mm Hg, peak at 0 minutes; pulse: by 6.6 mm Hg, peak at 5 minutes, p < .05 for both). There was a sustained increase in pulse wave velocity (by 0.57 m/s, p < .005) throughout the study denoting a sustained increase in aortic stiffness. Similarly, augmentation index showed a sustained increase with mental stress (by 6.16%, p < .05) denoting increased wave reflections from the periphery.",
            "output": [
                "Does acute mental stress have a prolonged unfavorable effect on arterial stiffness and wave reflections?"
            ]
        },
        {
            "id": "task847-17532a3725994c0faefa109bf8d20fde",
            "input": "The purpose of this study was to examine how variation in the beta-2 adrenergic receptor gene (ADRB2), in combination with the moderating influences of race, body mass index (BMI), and anger expression style (anger-in, anger-out), affects blood pressure (BP) at rest and in response to acute laboratory stress.', 'Four hundred fifty adolescents (mean age = 18.5 +/- 2.7 years; 228 [124 males] whites and 222 [110 males] blacks completed two stressors (video game challenge, forehead cold pressor). Hemodynamic measures were taken before, during, and after each stressor. Stressors were separated by a 20-minute rest period.', 'Frequency of detrimental haplotype (Gly16/Glu27) carrier status was greater among whites than blacks (p < .05). A significant three-way interaction among haplotype, BMI, and race for resting systolic blood pressure (SBP) found the highest BP level to be among high BMI carriers, but only for whites. A separate three-way interaction was found to be significant for haplotype, anger-in and race such that high anger-in carriers showed the highest level of resting SBP (p < .05) and total peripheral resistance (TPR) (p < .05) and the greatest TPR reactivity to the cold pressor task (p < .01). Post hoc analyses revealed these interactions with anger-in were only present among blacks. No significant interactions with anger-out for either ethnic group were observed.",
            "output": [
                "Do anger suppression and adiposity modulate association between ADRB2 haplotype and cardiovascular stress reactivity?"
            ]
        },
        {
            "id": "task847-8d7d451d86514611bacbb2dee623d7c8",
            "input": "Our aim is to document current imaging practices for diagnosing acute pulmonary embolism (PE) among physicians practicing in the United States and explore factors associated with these practices.', 'Between September 2004 and February 2005, we surveyed by mail 855 physicians selected at random from membership lists of three professional organizations. Physicians reported their imaging practices and experiences in managing patients with suspected acute PE during the preceding 12 months.', 'Completed questionnaires were received from 240 of 806 eligible participants (29.8%) practicing in 44 states: 86.7% of respondents believed that computed tomographic pulmonary angiography (CTPA) was the most useful imaging procedure for patients with acute PE compared with 8.3% for ventilation-perfusion (V-P) scintigraphy and 2.5% for conventional pulminary angiography (PA). After chest radiography, CTPA was the first imaging test requested 71.4% of the time compared with V-P scintigraphy (19.7%) and lower-limb venous ultrasound (5.8%). Participants received indeterminate or inconclusive results 46.4% of the time for V-P scintigraphy, 10.6% of the time for CTPA, and 2.2% of the time for PA. CTPA was available around the clock to 88.3% of participants compared with 53.8% for V-P scintigraphy and 42.5% for PA. A total of 68.6% of respondents received CTPA results in 2 hours or less (vs 37.5% for V-P scintigraphy and 22.9% for PA). CTPA also provided an alternative diagnosis to PE or showed other significant abnormalities 28.5% of the time, and these findings frequently altered management.",
            "output": [
                "Is cT pulmonary angiography the first-line imaging test for acute pulmonary embolism : a survey of US clinicians?"
            ]
        },
        {
            "id": "task847-50e8ebad6b6d4d34b644f48c68e40f1d",
            "input": "To determine the association of markers of regional neurodegeneration (ND) at autopsy to degree of neurocognitive impairment in persons with HIV.', 'In a prospectively followed cohort of HIV-infected individuals we examined the relationship between antemortem neuropsychological (NP) abilities and postmortem neuropathological data.', 'Twenty-seven HIV-infected individuals with both neuropsychological and neuropathological data were identified. Laser confocal scanning microscopy was used to determine the degree of ND based on: (1) microtubule-associated protein (MAP2; reflecting neuronal cell bodies and dendrites) and (2) synaptophysin (SYN; a measure of presynaptic terminals). A regional combined score, based on the distribution of percentage neuropil occupied by MAP2 and SYN and emphasizing severity of ND, was created for each brain region: midfrontal cortex, hippocampus, and putamen.', 'The regional combined scores from each brain region studied were better correlated with level of global NP impairment than measures of SYN and MAP2 individually. In a regression, hippocampal and putamen regional combined scores were independent predictors of degree of antemortem NP impairment (F(3,23) = 6.17; P < 0.01; R2 = 0.45). The correlations among regional ND measures demonstrated that ND is unevenly distributed across multiple brain regions.",
            "output": [
                "Is cortical and subcortical neurodegeneration associated with HIV neurocognitive impairment?"
            ]
        },
        {
            "id": "task847-3e6dbbcc2e3f4ee3952bf013be4f15e6",
            "input": "To study the cure rate and 5 year results of laparoscopic burch colposuspension for stress urinary incontinence in Thai women.', 'Twenty one Thai women with stress urinary incontinence attending the gynecology clinic at King Chulalongkorn Memorial hospital were recruited. Pre operative clinical and urodynamic evaluation were done. They underwent Laparoscopic burch colposuspension between January - December 1998. The cure rate was evaluated by clinical and urodynamic examination.', 'The mean +/- SD of operative time, blood loss and hospital stay were 70 +/- 20 min, 140 +/- 30 ml and 1.6 +/- 0.5 days respectively. The complication rate was 19.1% (Bladder injuries 2 cases, voiding difficulties 1 case and de novo detrusor overactivity 1 case). The objective cure rate at 5 years was 76.2%.",
            "output": [
                "Do five years follow up of laparoscopic burch colposuspension for stress urinary incontinence in Thai women?"
            ]
        },
        {
            "id": "task847-c810e4dda3e34b2c86c9eced8e78325c",
            "input": "The classical management of acne calls for prolonged oral and/or topical treatments; however, some patients request a rapid effect to make the papules disappear within a few hours or days.', 'To test the effect of a single overnight application of a paste containing 0.25% miconazole nitrate on acne papules, and comparison with the effect of the same but unmedicated paste.', 'Narrow-band reflectance spectroscopy was used to assess the changes in E index (erythema) after overnight application of the pastes. In the first study, a total of 117 acne papules were assessed in 15 adolescents. Measurements of the E index were performed at 24-h intervals for 4 days on acne papules and the surrounding normal-looking skin. The last two assessments were performed the mornings preceding and following, respectively, a single application of the medicated paste. The second part of the study consisted of a double-blind, split-face study on 25 adolescents with acne. They applied each of the two formulations on a randomized part of the forehead. A total of 161 acne papules received the medicated paste and 160 received the same but unmedicated paste. Measurements were performed the mornings before and after the overnight treatment.', 'In the first part of the study, no significant daily difference was observed between the three series of pretreatment E indices, on both acne papules and normal skin. The treatment did not affect the E index of normal skin. By contrast, it decreased significantly the E index of the acne papules. The second part of the study also showed that the medicated paste significantly decreased the E index of acne papules. This effect was significantly (P < 0.05) superior to that of the unmedicated paste.",
            "output": [
                "Do effect of a single overnight topical application of miconazole nitrate paste on acne papules?"
            ]
        },
        {
            "id": "task847-7a5bf08e8b694e3b82bb84053e6c40a4",
            "input": "Depression is a robust predictor of cardiovascular risk. In this study, we examined the association between depression measured in terms of symptom severity and treatment history, cardiac symptom presentation, and clinical outcomes among a sample of women with suspected myocardial ischemia.', 'Seven hundred fifty women with chest pain, mean age 53.4, completed a diagnostic protocol including depression measures, coronary angiogram, ischemia testing, and coronary disease risk factor assessment. Five hundred five participants also completed the Beck Depression Inventory. We further tracked participants over a mean 2.3-year period to evaluate subsequent cardiac events, hospitalization, and mortality.', 'Depression treatment history and current symptom severity were differentially associated with cardiac symptoms and outcomes. Both measures were reliably associated with coronary artery disease (CAD) risk factors and more severe cardiac symptoms. Depression symptom severity was linked to an increased mortality risk over follow-up (RR = 1.05; 95% CI, 1.01-1.09), whereas depression treatment history predicted an increased risk of hospitalization (RR = 1.3; 95% CI, 1.02-1.6), less severe CAD from angiogram, and a reduced likelihood of a positive ischemia test.",
            "output": [
                "Is depression associated with cardiac symptoms , mortality risk , and hospitalization among women with suspected coronary disease : the NHLBI-sponsored WISE study?"
            ]
        },
        {
            "id": "task847-fcf38dc1c8664f3aa294095dd264e4c1",
            "input": "The aim of this study was to examine the utility of a hierarchical algorithm incorporating codes from the International Classification of Functioning, Disability and Health--ICF (WHO, 2001) and the International Statistical Classification of Diseases-ICD (WHO, 1994) to classify reasons for eligibility of young children in early intervention.', 'The database for this study was a nationally representative enrollment sample of more than 5,500 children in a longitudinal study of early intervention. Reasons for eligibility were reviewed and matched to the closest ICF or ICD codes under one of four major categories (Body Functions/Structures, Activities/Participation, Health Conditions, and Environmental Factors).', 'The average number of reasons for eligibility provided per child was 1.5, resulting in a population summary exceeding 100%. A total of 305 ICF and ICD codes were used with most (77%) of the children having codes in the category of Body Function/Structures. Forty-one percent of the sample had codes of Health Conditions, whereas the proportions with codes in the Activities/Partipication and Environmental Categories were 10 and 5%, respectively.",
            "output": [
                "Do iCF and ICD codes provide a standard language of disability in young children?"
            ]
        },
        {
            "id": "task847-a12d603245e0449796e12c71160d8fae",
            "input": "To compare the Tardieu Scale as a clinical measure of spasticity after stroke with the Ashworth Scale.', 'Cross-sectional study.', 'Sixteen people, living in the community three years after their stroke.', 'The Ashworth Scale and Tardieu Scale as well as laboratory measures of spasticity (stretch-induced electromyographic (EMG) activity) and contracture (maximum passive joint excursion) were collected from the affected elbow flexors and extensors and ankle plantarflexors and dorsiflexors by three examiners who were blinded to the results of the other measures.', 'The percentage exact agreement (PEA) between the Tardieu Scale and a laboratory measure of spasticity was 100% for both the elbow flexors and ankle plantarflexors. This was significantly (P= 0.02) greater than the PEA of 63% for both muscles between the Ashworth Scale and the same laboratory measure of spasticity. For contracture, the PEA between the Tardieu Scale and a laboratory measure was 94% for both the elbow flexors and the ankle plantarflexors. Pearson correlation coefficients between the Tardieu Scale and laboratory measures of spasticity were 0.86 for the elbow flexors and 0.62 for the ankle plantarflexors and between the Tardieu Scale and laboratory measures of contracture were 0.89 for the elbow flexors and 0.84 for the ankle plantarflexors.",
            "output": [
                "Does the Tardieu Scale differentiate contracture from spasticity whereas the Ashworth Scale is confounded by it?"
            ]
        },
        {
            "id": "task847-5845d5348efe4a3d821f125d11fafe4a",
            "input": "To evaluate whether 1) a dedicated, multispecialty service, 2) a distinct hospital ward, 3) protocols, and 4) a specialist are associated with reduced mortality among patients with stroke.', 'The authors reviewed data (1998 and 1999) from all acute, non-federal hospitals in California, including administrative discharge databases for patient and hospital-level information, mortality data through 1 year post discharge, and a hospital-level survey regarding structural elements of stroke care. The impact of a dedicated, multidisciplinary stroke service and of stroke wards, protocols, and specialists on odds of death among patients with ischemic and hemorrhagic stroke were each examined using logistic regression models. How these elements of care impacted outcome at teaching vs non-teaching hospitals was also examined.', 'A 67.5% response rate (257/381) from surveyed hospitals provided data for 61,541 patients with stroke. A dedicated, multispecialty stroke service was available at 7.4% of hospitals. Twelve percent of hospitals had a stroke ward, 62.3% used protocols, and 16% had neurologists with specialty training in stroke. Patients cared for at hospitals with a dedicated stroke service had significantly lower odds for death at 30 days, and reduced mortality was maintained through 365 days after admission. Stroke wards, protocols, and specialists were not associated with reduced mortality. Having a dedicated stroke service was associated with reduced mortality at both non-teaching and teaching hospitals.",
            "output": [
                "Are multispecialty stroke services in California hospitals associated with reduced mortality?"
            ]
        },
        {
            "id": "task847-a14197736bd8434d85aae2499b880165",
            "input": "Systemic inflammation, insulin resistance, and endothelial dysfunction have been implicated in the development of cardiovascular disease in rheumatoid arthritis (RA). Since insulin resistance can promote endothelial dysfunction and anti-TNF-alpha blockade yield a rapid improvement of endothelial function, we have sought to assess whether TNF-alpha blockade may also result in a reduction of insulin serum levels and improvement of insulin resistance in RA patients who require this therapy because of severe and refractory disease.', 'We recruited patients with RA seen over a period of 1 month at Hospital Xeral-Calde, Lugo, Spain, that were on treatment with anti-TNF-alpha monoclonal antibody-infliximab. Patients with diabetes mellitus or plasma glucose > 110 mg/dl were excluded. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately prior to and after infliximab infusion.', 'Twenty-seven RA patients (21 women; mean age: 57.1 years; mean DAS28: 4.43) fulfilled the inclusion criteria. Dramatic reduction in the serum insulin levels and insulin/glucose index was observed following infliximab infusion. Also, a significant improvement of insulin resistance and insulin sensitivity was found.",
            "output": [
                "Does anti-tumor necrosis factor-alpha blockade improve insulin resistance in patients with rheumatoid arthritis?"
            ]
        },
        {
            "id": "task847-764fa3e4db2044c7b2bd19be68d967d3",
            "input": "Preexisting gastroesophageal reflux disease (GERD) and esophageal motility disorders may affect the outcome of laparoscopic adjustable gastric banding (AGB).', 'Prospective cohort study.', 'Tertiary referral center.', 'Between January 1, 1996, and December 31, 2002, AGB procedures were performed in 587 patients (mean body mass index, 46.7 [calculated as weight in kilograms divided by the square of height in meters]). The study population was composed of patients with preoperative GERD (assessed by a symptom-score questionnaire) and was divided into group 1 (those with preoperative GERD symptoms only) and group 2 (those with preoperative and postoperative GERD symptoms).', 'Laparoscopic AGB was performed according to the pars-flaccida technique.', 'All patients underwent preoperative and annual postoperative symptom scoring, endoscopy, esophageal barium swallow tests, esophageal manometry, and 24-hour pH monitoring.', 'Mean follow-up time was 33 months (range, 12-49 months). A total of 164 patients (27.9%) were diagnosed as having preoperative GERD symptoms. In 112 (68.3%) of these patients GERD symptoms vanished postoperatively (group 1), whereas 52 patients (31.7%) remained symptomatic after undergoing laparoscopic AGB implantation (group 2). Preoperatively, group 2 patients showed significantly poorer esophageal body motility compared with group 1 patients (20.8% vs 12.8% defective propagations; P = .007). In group 2 the mean symptom scores for dysphagia (0.4 vs 0.9) and regurgitation (0.6 vs 1.4) deteriorated significantly following laparoscopic AGB implantation, respectively. Eighteen patients (34.6%) in group 2 developed esophageal dilatation.",
            "output": [
                "Do prevalent esophageal body motility disorders underlie aggravation of GERD symptoms in morbidly obese patients following adjustable gastric banding?"
            ]
        },
        {
            "id": "task847-0b18db9535954c8899ce9c0a6ce67fab",
            "input": "To study the long-term effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease (PD).', \"One hundred fifty-seven de novo PD patients were randomized in a double-blind, placebo-controlled study of 7 years' duration. In the monotherapy part, selegiline significantly delayed the initiation of levodopa therapy vs placebo. The authors now report the results from the combination part of the study, in which 140 patients received selegiline or placebo in addition to individually tailored levodopa therapy.\", 'Compared with placebo, selegiline slowed the progression of disease disability as measured by the Unified Parkinson Disease Rating Scale (UPDRS) total score (p = 0.003) or by motor (p = 0.002) and Activities of Daily Living (p = 0.0002) subscores. After 5 years in combination therapy, the mean difference in the UPDRS total score was nearly 10 points, with patients receiving placebo having 35% higher scores. Simultaneously, patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline; after 5 years, the mean dosage of levodopa was 19% higher with placebo than with selegiline (p = 0.0002). Considering the entire (monotherapy and combination therapy) 7-year study time, there was a trend for selegiline to delay the start of wearing-off fluctuations (hazard ratio 0.55, p = 0.08). In both phases of the study, selegiline was safe and well tolerated.",
            "output": [
                "Does selegiline slow the progression of the symptoms of Parkinson disease?"
            ]
        },
        {
            "id": "task847-5f50cf49230e4c93a545648a87aaff40",
            "input": "D-lactate is the dextrorotatory form of L-lactate. L-lactate is the isomer routinely tested in clinical practice to assess cell hypoxemia. D-lactate has been recently proposed as a specific marker of gut ischemia-reperfusion (IR), particularly after surgery for ruptured aortic aneurysms. We sought to assess D-lactate as a reliable marker of gut IR in a rat model of supraceliac aortic clamping.', 'Prospective, randomized trial.', 'Animal research center.', 'Male Wistar rats.', 'After general anesthesia, rats were randomized into two groups (n = 8 in each). The IR group underwent a laparotomy, aortic clamping for 40 mins, and 1 hr of reperfusion. The control group underwent the same procedure, except for aortic clamping.', 'The following variables were tested after 1 hr of reperfusion (IR group) or after the equivalent time (control group): 1) tissue and cell insult via ileum morphometry and electron microscopy, serum glutamic transaminases (serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase), pH, and L-lactate; 2) systemic inflammatory response via tumor necrosis factor-alpha; and 3) D-lactate levels. After IR, mucous membrane thickness and villi height decreased significantly, respectively by 30% and 45%, and electron-microscopic examination showed typical IR mucous membrane cell insult. IR also caused lactic acidosis (pH = 7.16 +/- 0.05 vs. 7.31 +/- 0.02, p < .01; L-lactate = 7.1 +/- 1.6 vs. 1.6 +/- 0.4 mmol/L, p = .001) and increased blood levels of transaminases. Concurrently, the inflammatory response was characterized by an increase in tumor necrosis factor-alpha (213 +/- 129 vs. 47 +/- 32 pg/mL, p < .05). However, blood levels of D-lactate never increased after IR.",
            "output": [
                "Is d-lactate a reliable marker of gut ischemia-reperfusion in a rat model of supraceliac aortic clamping?"
            ]
        },
        {
            "id": "task847-b69bb92a6c824830aba0328602100511",
            "input": "Environmental tobacco smoke (ETS) is a major threat to public health, associated with a number of serious diseases, and a leading cause of death. Previous research demonstrates that enactment of government policies mandating clean indoor air is effective in creating more smoke-free public places and decreasing the incidence of smoking. Both researchers and community activists have an interest in understanding the factors that predict support for the regulation of ETS.', 'This study examined predictors of support for regulating ETS by surveying 684 city and county public officials in Colorado who were interviewed by phone and mail (response rate 61%).', 'Thirty-five percent of public officials reported that it is a \"serious\" or \"very serious\" problem that nonsmokers breathe in other people\\'s cigarette smoke, 21% were \"neutral,\" and 42% said that it was \"not serious\" or \"not serious at all.\" Results indicated that support for policies to control ETS and promote clean indoor air is significantly more prevalent among public officials who: (1) believe that tobacco use is a serious problem in their community, (2) believe that breathing environmental tobacco smoke is a serious problem for nonsmokers, (3) believe that city and county government should get involved with people\\'s decisions about smoking, (4) support smoking-cessation programs for public employees, and (5) have smoked less than 100 cigarettes during their lifetime.",
            "output": [
                "Does predictors of support for environmental tobacco smoke ban in state government?"
            ]
        },
        {
            "id": "task847-409e5e43d7d2429997714daae9a9c64c",
            "input": "Genetic and environmental variation are both known to influence development. Evolution of a developmental response that is optimized to the environment (adaptive plasticity) requires the existence of genetic variation for that developmental response. In complex traits composed of integrated sets of subsidiary traits, the adaptive process may be slowed by the existence of multiple possible integrated responses. This study tests for family (sibship) specific differences in plastic response to hypoxia in an integrated set of cardiovascular traits in zebrafish.', 'Cardiac output, which is the integrated product of several subsidiary traits, varied highly significantly between families, and families differed significantly in the degree and direction of response to developmental oxygen level. The cardiac output response to oxygen environment was entirely family specific with no significant overall trend due to oxygen level. Constituent physiological variables that contribute to cardiac output all showed significant family specific response to hypoxia. Traits that were not directly related to cardiac output, such as arterial and venous diameter, and red blood cell velocities did not respond to hypoxia in a family specific manner.",
            "output": [
                "Does cardiovascular system in larval zebrafish respond to developmental hypoxia in a family specific manner?"
            ]
        },
        {
            "id": "task847-7275724fcea444c9847c3948e7e60d0d",
            "input": "Renal dysfunction is common after liver transplantation (LT). The aim of our study was to assess the prevalence of renal dysfunction 5 yr after LT and to identify risk factors for the development of this complication.', 'A total of 134 adult patients underwent LT from 1987 to 1998 and 74.6% of them were alive 5 yr after. Pre-LT, 1 and 5 yr post-LT renal function were calculated by Cockroft and modification of diet in renal disease (MDRD) formula. Since 1987 glomerular filtration rate (GFR) has been measured by radiolabeled tracers clearance (RTC). Risk factors for GFR < 50 mL/min were analyzed using a multivariate logistic regression model.', 'Mean pre-LT GFR was 79 and 85 mL/min with Cockroft and MDRD respectively; 11% of the patients had a GFR <or= 50 mL/min. 5 yr after LT, mean GFR was 63, 61 and 70 mL/min with MDRD, Cockroft and RTC respectively, GFR decreased by 26%, and 25% of the patients had a GFR < 50 mL/min. Independent risk factors associated with impaired renal function were: trough levels of cyclosporin A (CyA) >or= 150 microg/L or tacrolimus (FK) >or= 10 microg/L at 1 yr and CyA >or= 100 microg/L or FK >or= 8 microg/L at 5 yr.",
            "output": [
                "Is long-term renal function after liver transplantation related to calcineurin inhibitors blood levels?"
            ]
        },
        {
            "id": "task847-ffa7cac7f28e4671969d9ca9eb65730b",
            "input": "To determine if the presence of perineural invasion (PNI) predicts biochemical recurrence in patients who underwent low-dose-rate brachytherapy for the treatment of localized prostate cancer.', 'A retrospective case control matching study was performed. The records of 651 patients treated with brachytherapy between 1996 and 2003 were reviewed. Sixty-three of these patients developed biochemical failure. These sixty-three patients were then matched in a one-to-one ratio to patients without biochemical failure, controlling for biopsy Gleason score, clinical stage, initial prostate-specific antigen, age, and the use of androgen deprivation. The pathology of the entire cohort was then reviewed for evidence of perineural invasion on initial prostate biopsy specimens. The biochemical relapse free survival rates for these two groups were compared.', 'Cases and controls were well matched, and there were no significant differences between the two groups in age, Gleason grade, clinical stage, initial prostate-specific antigen, and the use of androgen deprivation. PNI was found in 19 (17%) patients. There was no significant difference in the rates of PNI between cases and controls, 19.6% and 14.3% respectively (p = 0.45). PNI did not correlate with biochemical relapse free survival (p = 0.40).",
            "output": [
                "Does perineural invasion on prostate needle biopsy predict biochemical failure following brachytherapy for prostate cancer?"
            ]
        },
        {
            "id": "task847-6b2213ce19f84c62b01ca649df6a2d92",
            "input": "To investigate a putative increased risk of rectal cancer subsequent to prostatic radiotherapy.', 'In an analysis of the Surveillance, Epidemiology, and End Results registry, we compared men who had radiotherapy for prostatic carcinoma with those treated surgically and those treated with neither modality. Kaplan-Meier analyses for the time to failure from rectal cancer were performed between age-matched subgroups of the three cohorts. Cox proportional hazards analyses were performed to ascertain what influences might affect the incidence of subsequent rectal cancer.', 'In all, 33,831 men were irradiated, 167,607 were treated surgically, and 36,335 received neither modality. Rectal cancers developed in 243 (0.7%) of those irradiated (mean age, 70.7 years), 578 (0.3%) of those treated surgically (68.7 years), and 227 (0.8%) of those treated with neither modality (74.2 years). When age effects and the differences between the surgical and untreated cohorts were controlled for, we were unable to demonstrate any significant increased incidence of rectal cancer in men irradiated for prostatic cancer.",
            "output": [
                "Is prostatic irradiation associated with any measurable increase in the risk of subsequent rectal cancer?"
            ]
        },
        {
            "id": "task847-da9ce90acf0548d399d435460ea833de",
            "input": "Autoimmune hepatitis type 2 (AIH-2), a severe juvenile liver disorder of unknown etiology and pathogenesis, is characterized by liver-kidney microsomal antibody type 1 targeting cytochrome P450IID6 (CYP2D6) and is associated to HLA DRB1*07. Although CYP2D6 B-cell reactivity has been extensively characterized, little is known about CYP2D6-specific T-cell responses. The aim of the present study was to characterize anti-CYP2D6 cellular immune responses and their possible pathogenic role in patients with AIH-2.', 'We investigated T-cell reactivity against 61 overlapping peptides spanning the full CYP2D6 protein using ex vivo cultures obtained at diagnosis, remission, and relapse. Moreover, CYP2D6-specific T-cell reactivity was investigated in the context of HLA restriction, peptide-binding affinity to HLA DRB1*07, cytokine profile, disease specificity, and clinical course.', 'Proliferative responses to CYP2D6 cluster to 7 antigenic regions in DRB1*07 and to 4 regions in non-DRB1*07 patients. Whereas distinct peptides induce production of interferon gamma, interleukin-4, or interleukin-10, peptides inducing interferon-gamma and proliferation overlap. There is also an overlap between sequences inducing T- and B-cell responses. The breadth (number of epitopes) and intensity (quantity of cytokine produced) of the T-cell response are directly correlated to disease activity (biochemical and histologic markers).",
            "output": [
                "Are polyclonal T-cell responses to cytochrome P450IID6 associated with disease activity in autoimmune hepatitis type 2?"
            ]
        },
        {
            "id": "task847-ced0fc29a6ad4c919a59462e1b553f78",
            "input": "HBV covalently closed circular DNA (cccDNA), the replicative intermediate responsible for persistent HBV infection of hepatocytes, is the template for transcription of all viral mRNAs. Nuclear cccDNA accumulates as a stable episome organized into minichromosomes by histone and nonhistone proteins. In this study we investigated, by a newly developed sensitive and specific assay, the relationship between viral replication and HBV chromatin assembly, transcription, and interaction with viral and cellular regulatory proteins.', 'To achieve this aim we coupled a quantitative chromatin immunoprecipitation (ChIP) technique to an established method that allows the amplification of virion-encapsidated HBV genomes after transfection of linear HBV DNA into human hepatoma HuH7 cells. The cccDNA-ChIP technique was also applied to study HBV minichromosome transcriptional regulation in liver tissue from HBV-infected patients.', 'The use of anti-acetyl-H4/-H3 specific antibodies to immunoprecipitate transcriptionally active chromatin revealed that HBV replication is regulated by the acetylation status of the cccDNA-bound H3/H4 histones. Class I histone deacetylases inhibitors induced an evident increase of both cccDNA-bound acetylated H4 and HBV replication. Finally, histones hypoacetylation and histone deacetylase 1 recruitment onto the cccDNA in liver tissue correlated with low HBV viremia in hepatitis B patients.",
            "output": [
                "Is hepatitis B virus replication regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 histones?"
            ]
        },
        {
            "id": "task847-ba458cfd587e4686aa4de6c72ebdd66a",
            "input": "The mental gland pheromone of male Plethodon salamanders contains two main protein components: a 22 kDa protein named Plethodon Receptivity Factor (PRF) and a 7 kDa protein named Plethodon Modulating Factor (PMF), respectively. Each protein component individually has opposing effects on female courtship behavior, with PRF shortening and PMF lengthening courtship. In this study, we test the hypothesis that PRF or PMF individually activate vomeronasal neurons. The agmatine-uptake technique was used to visualize chemosensory neurons that were activated by each protein component individually.', 'Vomeronasal neurons exposed to agmatine in saline did not demonstrate significant labeling. However, a population of vomeronasal neurons was labeled following exposure to either PRF or PMF. When expressed as a percent of control level labeled cells, PRF labeled more neurons than did PMF. These percentages for PRF and PMF, added together, parallel the percentage of labeled vomeronasal neurons when females are exposed to the whole pheromone.",
            "output": [
                "Do male pheromone protein components activate female vomeronasal neurons in the salamander Plethodon shermani?"
            ]
        },
        {
            "id": "task847-30372629797c441c844e1fdd2b1426a0",
            "input": "Fracture and low bone mineral density both have strong predictive value for future fractures. The risk of future fractures can be reduced by medi-cal treatment if patients with osteoporosis are identified, for example by screening fracture patients for low bone mineral density. We suggest that these screening routines be organized at orthopedics departments and we report our experience with such a screening system.', 'We screened all patients between 50-75 years of age with a wrist, vertebral, proximal humerus, or hip fracture visiting our orthopedics department by measuring bone mineral density (BMD) using DEXA scans. After diagnosis, the patients were referred to their primary care physician for treatment.', 'Between November 1, 2002, and October 31, 2003, 239 patients were investigated and only 13% had normal BMD values. 45% of the patients were diagnosed with osteopenia and 42% with osteoporosis.",
            "output": [
                "Is one fracture enough ! Experience with a prospective and consecutive osteoporosis screening program with 239 fracture patients?"
            ]
        },
        {
            "id": "task847-93ba48bcfea047309f68abe11e22675f",
            "input": "Cartilage degeneration often occurs after osteosynthesis of a devascularized intermediary fragment in a joint fracture, in mosaicplasty or in whole-joint toe-to-finger transplantation. Hypothetically, the degeneration is secondary to a collapse of the transferred subchondral bone as it remodels during high mechanical load. Bisphosphonates are used to reduce resorption of necrotic bone. We tested a systemic pretreatment before harvesting the graft in order to protect the bone and cartilage against collapse and secondary arthrosis.', 'Rats were given one zoledronate injection and bone grafts were harvested. The grafts were frozen, thawed and placed into bone chambers, and implanted into another batch of rats. Graft resorption and new bone formation was measured by histomorphometric analysis and compared with untreated grafts.', 'In the remodeled area of the controls, the graft was almost totally resorbed and replaced by bone marrow. In the zoledronate-treated specimens, the graft remained and the graft trabeculas were lined with new bone. By histomorphometry, the total amount of bone (graft plus new bone) within the remodeled area was 16% in the zoledronate-treated grafts and 5% in the controls (p = 0.003).",
            "output": [
                "Does systemic zoledronate precoating of a bone graft reduce bone resorption during remodeling?"
            ]
        },
        {
            "id": "task847-7b3a6f601b4541e68769904bc05d12f3",
            "input": "Prospective studies of the role of psychological stress in ulcerative colitis are inconsistent or show a modest relationship. We tested the hypothesis that individual differences in autonomic function are associated with differences in the disease course of ulcerative colitis.', 'The spectral power of heart rate variability, an indirect marker of autonomic function, was measured during a standardized stress protocol in 93 ulcerative colitis patients. Patients were categorized as typical or atypical by an increase or decrease, respectively, in the high frequency band of heart rate variability from a period of acute stress to recovery 5 min later. Disease activity was measured at baseline (time 1) and a second time point (time 2) 7-37 months later.', 'An atypical pattern of heart rate variability at time 1, present in 29% of patients, was associated with lower mean disease activity at time 2 (atypical, 0.56+/-0.93; typical, 2.27+/-2.56, P=0.001). The contribution of heart rate variability pattern to explaining time 2 disease activity was independent of the contributions of other factors that differed between groups, including time 1 disease activity and lifetime corticosteroid use.",
            "output": [
                "Does autonomic response to standardized stress predict subsequent disease activity in ulcerative colitis?"
            ]
        },
        {
            "id": "task847-b7bc27221e4947edaa9b02ce719cb272",
            "input": "Recent studies have shown the apolipoprotein B to apolipoprotein A1 ratio (apoB/A1) to be superior to LDL-cholesterol measurements to predict cardiovascular events. The present study aims to relate apoB/A1 to endothelium-dependent vasodilation, an early marker of atherosclerosis, in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study.', 'In this population-based study, 1016 subjects aged 70 years were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. EDV and the pulse wave response, but not FMD, were related to apoB/A1 levels (r=-0.11, p=0.0038 for EDV, r=-0.16, p<0.0001 for the pulse wave analysis and r=0.01, p=0.65 for FMD). Neither LDL-cholesterol, nor non-HDL-cholesterol, was significantly related to the measurements of endothelium-dependent vasodilation. Also endothelium-independent vasodilation (EIDV) evaluated by the invasive forearm technique with sodium nitroprusside was related to apoB/A1 levels (r=-0.12, p<0.0016).",
            "output": [
                "Is vasodilation in resistance arteries related to the apolipoprotein B/A1 ratio in the elderly : the Prospective Investigation of the Vasculature in Uppsala Seniors ( PIVUS ) study?"
            ]
        },
        {
            "id": "task847-74febb48a7b742099c6218dec96279d3",
            "input": "The management of patients with recurrent colorectal liver metastases (RCLM) remains controversial. This study aimed to determine whether repeat liver resection for RCLM could be performed with acceptable morbidity, mortality and long-term survival.', \"Of 1121 consecutive liver resections performed and prospectively analysed between 1987 and 2005, 852 'curative' resections were performed on patients with colorectal liver metastases. Single liver resection was performed in 718 patients, and 71 repeat hepatic resections for RCLM were performed in 66 patients.\", 'There were no postoperative deaths following repeat hepatic resection compared with a postoperative mortality rate of 1.4 per cent after single hepatic resection. Postoperative morbidity was comparable following single and repeat hepatectomy (26.1 versus 18 per cent; P = 0.172), although median blood loss was greater during repeat resection (450 versus 350 ml; P = 0.006). Actuarial 1-, 3- and 5-year survival rates were 94, 68 and 44 per cent after repeat hepatic resection for RCLM, compared with 89.3, 51.7 and 29.5 per cent respectively following single hepatectomy.",
            "output": [
                "Is repeat hepatic resection for recurrent colorectal liver metastases associated with favourable long-term survival?"
            ]
        },
        {
            "id": "task847-b8983807f8ed44829b121ed22eb132c3",
            "input": ". We aimed to evaluate the effectiveness of a multifaceted intervention, targeting staff-patient communication, in improving emergency department patient satisfaction.', 'We undertook a pre- and post-intervention study in a university-affiliated emergency department, over a 12-month period. The intervention included communication workshops, a patient education film, and a patient liaison nurse. At the patient level, the patient liaison nurse ensured optimal staff-patient community communication and played a role in staff communication education. The intervention was evaluated using patient surveys (containing general and communication-specific satisfaction items scored out of 100), complaint rates, and patient liaison nurse activity data.', \"A total of 321 and 545 patients returned questionnaires in the pre- and post-intervention periods, respectively. Significant improvements were observed in patients' perceptions of being 'informed about delays' [score difference, 5.3; 95% confidence interval (CI), 0.6-10.0], that 'staff cared about them as a person' (difference, 4.4; 95% CI, 0.7-8.1), the overall emergency department facility assessment (difference, 3.9; 95% CI, 0.4-7.5) and overall emergency department care (difference, 3.8; 95% CI, 0.3-7.3). Non-significant improvements were seen in all other satisfaction items. In the post-intervention period, there was a 22.5% (95% CI, 14.6-32.8) decrease in the number of complaints received and a decrease in the complaint rate of 0.7 (95% CI, -0.3 to 1.6) complaints per 1000 patients. The patient liaison nurse activities included orientation of the patient including (i) explanation of tests, procedures, and delays; (ii) communication with a range of hospital staff; and (iii) general comfort measures including analgesia quality control.",
            "output": [
                "Does a multifaceted intervention improve patient satisfaction and perceptions of emergency department care?"
            ]
        },
        {
            "id": "task847-d505829e6d2e45b38d7efd8b27cf12b2",
            "input": "Abnormalities of lung coagulation and fibrinolysis in sarcoidosis are thought to play a role in the pathogenesis of this disease.', 'We previously showed that bronchoalveolar lavage fluid (BALF) D dimer directly correlated with various measures of severity in sarcoidosis. Here, we analyze our observation that BALF D dimer was more frequently found at higher levels in African-American patients with pulmonary sarcoidosis.', 'BALF D dimer was measured in 55 subjects with pulmonary sarcoidosis and 31 healthy volunteers by enzyme immunoassay. The healthy group established a normal range of BALF D dimer with 71 ng/ml as the highest measured level. This was the cut point for comparisons among the patients with sarcoidosis.', 'High BALF D dimer levels (>71 ng/ml) were found in younger patients with sarcoidosis and were associated with a significantly lower percent predicted forced expiratory volume in 1 s and greater numbers of BAL lymphocytes. Black patients with sarcoidosis had higher BALF D dimer levels (median 131, range 0-2,040 ng/ml) than white patients (median 18, range 0-605 ng/ml; p = 0.011). Higher than normal BALF D dimer levels were found in 61% of the black subjects with sarcoidosis, but in only 20% of the white individuals (chi(2) = 5.539, p = 0.019). BALF D dimer was the only disease measure that discriminated black from white individuals with sarcoidosis.",
            "output": [
                "Are bronchoalveolar lavage fluid D dimer levels higher and more prevalent in black patients with pulmonary sarcoidosis?"
            ]
        },
        {
            "id": "task847-b9c1bbfc15f84b06b4ee4256a3abd91d",
            "input": "To determine the cost-effectiveness of averting the burden of disease. We used secondary population data and metaanalyses of various government-funded services and interventions to investigate the costs and benefits of various levels of treatment for rheumatoid arthritis (RA) and osteoarthritis (OA) in adults using a burden of disease framework.', 'Population burden was calculated for both diseases in the absence of any treatment as years lived with disability (YLD), ignoring the years of life lost. We then estimated the proportion of burden averted with current interventions, the proportion that could be averted with optimally implemented current evidence-based guidelines, and the direct treatment cost-effectiveness ratio in dollars per YLD averted for both treatment levels.', 'The majority of people with arthritis sought medical treatment. Current treatment for RA averted 26% of the burden, with a cost-effectiveness ratio of dollar 19,000 per YLD averted. Optimal, evidence-based treatment would avert 48% of the burden, with a cost-effectiveness ratio of dollar 12,000 per YLD averted. Current treatment of OA in Australia averted 27% of the burden, with a cost-effectiveness ratio of dollar 25,000 per YLD averted. Optimal, evidence-based treatment would avert 39% of the burden, with an unchanged cost-effectiveness ratio of dollar 25,000 per YLD averted.",
            "output": [
                "Is evidence-based medicine affordable : the cost-effectiveness of current compared with optimal treatment in rheumatoid and osteoarthritis?"
            ]
        },
        {
            "id": "task847-c9215a397c894177b6902462a8229be8",
            "input": "Escalation in monocyte trafficking from the bone marrow into the brain may play a critical role in central nervous system injury and cognitive deterioration in patients with HIV infection. This study tested the hypothesis that the mean diffusivity is sensitive to marrow changes in HIV patients and that these quantitative imaging measurements correlate with the severity of dementia.', 'The mean diffusivity (MD), determined for clival and calvarial marrow regions, was compared in 11 HIV-infected patients and 9 control subjects. The imaging measurements were also evaluated for relationships with dementia severity and markers of disease progression (CD4 and viral load in plasma).', 'The MD was significantly reduced in both clival and calvarial marrow in HIV-infected patients (P =.006). Diffusion measurements for clival (P =.02) and for calvarial (P =.03) regions were significantly correlated with the severity of dementia.",
            "output": [
                "Do bone marrow diffusion measures correlate with dementia severity in HIV patients?"
            ]
        },
        {
            "id": "task847-cc9847d6183a42409023817224f27f09",
            "input": "To determine the mechanisms of Bacillus subtilis spore killing by and resistance to an acidic solution containing Fe(3+), EDTA, KI and ethanol termed the KMT reagent.', 'Wild-type B. subtilis spores were not mutagenized by the KMT reagent but the wild-type and recA spores were killed at the same rate. Spores (alpha(-)beta(-)) lacking most DNA-protective alpha/beta-type small, acid-soluble spore proteins were less resistant to the KMT reagent than wild-type spores but were also not mutagenized, and alpha(-)beta(-) and alpha(-)beta(-)recA spores exhibited nearly identical resistance. Spore resistance to the KMT reagent was greatly decreased if spores had defective coats. However, the level of unsaturated fatty acids in the inner membrane did not determine spore sensitivity to the KMT reagent. Survivors in spore populations killed by the KMT reagent were sensitized to killing by wet heat or nitrous acid and to high salt in plating medium. KMT reagent-killed spores had not released their dipicolinic acid (DPA), although these killed spores released their DPA more readily when germinated with dodecylamine than did untreated spores. However, KMT reagent-killed spores did not germinate with nutrients or Ca(2+)-DPA and were recovered only poorly by lysozyme treatment in a hypertonic medium.",
            "output": [
                "Do mechanisms of Bacillus subtilis spore killing by and resistance to an acidic Fe-EDTA-iodide-ethanol formulation?"
            ]
        },
        {
            "id": "task847-a7ba287df5c044fcacf9c7f754f970b5",
            "input": "Emphysema, especially in the upper lobes, is frequently observed in association with idiopathic pulmonary fibrosis (IPF). However, the combination of emphysema plus IPF has received little attention.', 'To investigate the additional functional impairment from emphysema in IPF patients.', 'Twenty-one patients (mean age 66 y, 20 men) (Group I) who had both IPF (mean 35% of total lung volume) and emphysema (mean 14% of total lung volume) were compared to a group of 21 subjects who had IPF but no emphysema (Group II). The groups were matched for (among other criteria) the total extent of disease. Pulmonary function tests, Medical Research Council dyspnea score, 6-min walk test, and radiographic extents of both IPF and emphysema were obtained for each patient. The Composite Physiologic Index was calculated. In the total population (n = 42), the independent contributions of IPF and emphysema to several physiologic variables were investigated by using stepwise multiple regression analysis.', 'Despite the limited extent of emphysema, Groups I and II had similar physiologic impairment. Only residual volume and total lung capacity were significantly higher in Group I. According to stepwise multiple regression analysis, the extent of IPF and either the presence or the extent of emphysema in the total population were independent and significant predictors of dyspnea score, 6-min walk test, P(aO2), forced expiratory volume in the first second (FEV(1)), forced vital capacity (FVC), FEV1/FVC, the diffusing capacity of the lung for carbon monoxide, carbon monoxide diffusing capacity adjusted for alveolar volume (gas-transfer coefficient), and residual volume. The Composite Physiologic Index was closely related to the extent of IPF (r = 0.65, p < 0.0001) and to the dyspnea score (rho = 0.59, p < 0.0001).",
            "output": [
                "Does the presence of emphysema further impair physiologic function in patients with idiopathic pulmonary fibrosis?"
            ]
        },
        {
            "id": "task847-d7c5cb514d6b4826868d71fdd3c869ad",
            "input": "This study examines the ABCG1-mediated cholesterol efflux and intracellular cholesterol transport by studying the ABCG1 localization and function in macrophages.', 'HEK 293 cell overexpressing ABCG1, RNA interference, or macrophages from ABCG1 or ABCG4 knockout mice were used. ABCG1 but not ABCG4 had a major role in the increased cholesterol mass efflux produced by treatment of macrophages with LXR activators. In 293 cells, ABCG1 was found in the plasma membrane, Golgi, and recycling endosomes. In contrast, in basal macrophages, ABCG1 was predominantly intracellular, and redistributed to the plasma membrane after LXR activation. LXR activation increased macrophage cholesterol efflux to high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cyclodextrin in an ABCG1-dependent fashion. Suppression of ABCG1 expression increased cholesteryl ester formation and decreased SREBP2 target gene expression in macrophages, even in the absence of HDL acceptors.",
            "output": [
                "Does lXR-induced redistribution of ABCG1 to plasma membrane in macrophages enhance cholesterol mass efflux to HDL?"
            ]
        },
        {
            "id": "task847-9646d462bda44e8a983c7553affc242f",
            "input": "Physiological roles of apelin and its specific receptor APJ signaling were investigated in vascular smooth muscle cells (VSMCs). The present study determined whether apelin activates myosin light chain (MLC), a major regulatory event in initiating smooth muscle contraction.', 'To assess MLC activation, we performed Western blot and immunohistochemical studies using an antibody against the phospho-MLC. In VSMCs, apelin induces the phosphorylation of MLC in a concentration-dependent manner with a peak at 2 minutes. Pretreatment of VSMCs with pertussis toxin abolishes the apelin-induced phosphorylation of MLC. Inhibition of protein kinase C (PKC) with GF-109203X markedly attenuated the apelin-induced MLC phosphorylation. In addition, methylisobutyl amiloride, a specific inhibitor of the Na+/H+ exchanger (NHE), and KB-R7943, a potent inhibitor for the reverse mode of the Na+/Ca2+ exchanger (NCX), significantly suppressed the action of apelin. In wild-type mice, apelin phosphorylates MLC in vascular tissue, whereas it had no response in APJ-deficient mice by Western blot and immunohistochemistry. Apelin-induced phosphorylation of MLC was accompanied with myosin phosphatase target subunit phosphorylation.",
            "output": [
                "Does apelin stimulate myosin light chain phosphorylation in vascular smooth muscle cells?"
            ]
        },
        {
            "id": "task847-88570830cb01467fb0d77985f6235d2b",
            "input": "Riboflavin deficiency is common in many parts of the world, particularly in developing countries. The use of riboflavin-producing strains in the production of dairy products such as fermented milk, yogurt, and cheese is feasible and economically attractive because it would decrease the costs involved during conventional vitamin fortification and satisfy consumer demands for healthier foods. The present study in a rat bioassay assessed the response of administration of yogurt containing a riboflavin-producing strain of Propionibacterium freudenreichii on the riboflavin status of deficient rats.', 'Propionibacterium freudenreichii NIZO B2336 is a spontaneous roseoflavin-resistant mutant derived from P. freudenreichii B374 that produces larger amounts of riboflavin than the parental stain. Rats were fed a riboflavin-deficient diet for 21 d (depletion period), after which this same diet was supplemented with conventional yogurt, yogurt containing the riboflavin-producing strain (B2336), or the parental non-producing strain (B374) and fed to animals for 28 d (repletion period). As controls, rats were fed the same diet with different concentrations of commercial riboflavin.', 'The novel fermented product containing P. freudenreichii B2336, with increased levels of riboflavin, eliminated most physiologic manifestations of ariboflavinosis such as stunted growth, high erythrocyte glutathione reductase activation coefficient values, and hepatomegaly that were observed when using a riboflavin depletion-repletion model, whereas the product fermented with the non-riboflavin-producing strain did not show this beneficial effect.",
            "output": [
                "Does a novel dairy product fermented with Propionibacterium freudenreichii improve the riboflavin status of deficient rats?"
            ]
        },
        {
            "id": "task847-cefb817c69634973b1f943af30c05584",
            "input": "Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at average risk for the development of colorectal cancer regardless of gender or race/ethnicity. We determined the influence of gender and race/ethnicity on the cost-effectiveness of recommended colorectal cancer screening regimens.', 'We determined age-specific colorectal cancer incidence rates; the proportion of left-sided cancers; and the proportion of localized cancers in Asian, black, Latino and white men and women using the California Cancer Registry. We incorporated these data and available data for life expectancy and colorectal cancer survival to model the cost-effectiveness of two 35-year colorectal cancer-screening interventions.', 'Age-specific colorectal cancer incidence rates were highest in black men and lowest in Latino women. Screening beginning at age 50 was most cost-effective in black men and least cost-effective in Latino women (measured as dollars spent per year of life saved) using annual fecal occult blood testing combined with flexible sigmoidoscopy every five years and using colonoscopy every 10 years. The cost-effectiveness of a 35-year screening program in black men beginning at age 45 was similar to the cost-effectiveness of screening white men and black women beginning at age 50 and more cost-effective than screening nonblack women as well as Asian and Latino men beginning at age 50.",
            "output": [
                "Do gender and race/ethnicity affect the cost-effectiveness of colorectal cancer screening?"
            ]
        },
        {
            "id": "task847-2d3768d4c952464495456953e7750e2c",
            "input": "To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation,at 14 and 40 d after ligation when portal pressure is spontaneously normalized.', 'Adult male Wistar rats were divided into four groups: Group I: Sham14d , sham operated; Group II: PH14d , portal vein stenosis; (both groups were used 14 d after surgery); Group III: Sham40d, Sham operated and Group IV: PH40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia,plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected,were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded.', 'Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished.",
            "output": [
                "Does altered blood-brain barrier permeability in rats with prehepatic portal hypertension turn to normal when portal pressure is lowered?"
            ]
        },
        {
            "id": "task847-96508ad7c64845c6b98e6f984bc4be94",
            "input": "Many bacterial meningitis patients experience neurological or neuropsychological sequelae, predominantly deficits in short-term memory, learning, and attention. Neuropsychological symptoms after viral meningitis are observed less frequently. Sleep disturbance has been reported after both viral and bacterial meningitis.', 'To examine systematically the frequency and extent of sleep disturbance in meningitis patients.', 'Eighty six viral or bacterial meningitis (onset of acute disease at least 1 year previously) patients were examined using two standardised questionnaires (Schlaffragebogen B and the Pittsburgh Sleep Quality Index, PSQI) in conjunction with a standardised neurological examination, and compared to a control group of 42 healthy age-matched volunteers.', 'Patients after both viral and bacterial meningitis described their sleep as reduced in quality and less restful than that of healthy control subjects; both patient groups had a pathological mean PSQI total score. Impaired sleep scores after meningitis were not correlated to either the Glasgow Coma Scale or the Glasgow Outcome Scale. Moreover, no relationship between residual neurological dysfunction or depressivity and sleep quality was observed.",
            "output": [
                "Are sleep disorders long-term sequelae of both bacterial and viral meningitis?"
            ]
        },
        {
            "id": "task847-daa8321cd71c4ccc8eaa5a598d8e4541",
            "input": "Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain.', 'To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model.', 'The up-and-down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague-Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10-minute mortality and survival time.', 'All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive respiratory depression (7/11 deaths; p = 0.09). Ketamine (7/8 deaths) was ineffective as an antidote. Survival times also were prolonged in the diazepam and xylazine groups (log-rank p < 0.001) and, to a lesser degree, the morphine group (p = 0.07).",
            "output": [
                "Do multiple centrally acting antidotes protect against severe organophosphate toxicity?"
            ]
        },
        {
            "id": "task847-ea18f8e6da5846f8ad3ef1effa6bc055",
            "input": "The literature seldom specifies the location or method of measurement of ST segment elevation (STE) for determining eligibility in reperfusion trials. The objective of this study was to assess if different methods of measurement of STE in precordial leads of patients with anterior acute myocardial infarction due to left anterior descending occlusion result in significantly different scores.', 'This was a retrospective review of diagnostic electrocardiograms (ECGs) of consecutive patients presenting to our emergency department with acute myocardial infarction who had emergent primary percutaneous coronary intervention, left anterior descending occlusion, and no bundle branch block. STE was measured at the J point and at 60 milliseconds after the J point, relative to the PR segment, in leads V1-V6. STE by the two methods was compared for each lead, as were ST scores (sum of STE in leads V1-V6) and the sum of the STE in V2-V4. Eligibility for reperfusion therapy using 1-mm and 2-mm STE criteria in two consecutive anterior leads, as well as ST scores and the sum of the STE in V2-V4, were evaluated.', 'Thirty-seven ECGs were analyzed. Mean ST measurements in every lead were significantly lower when measured at the J point versus 60 milliseconds after the J point, as were ST scores (9.7 +/- 2.14 mm vs. 14.9 +/- 2.69 mm; p < 0.00001). Fewer ECGs met enrollment criteria when based on STE at the J point versus at 60 milliseconds after the J point. Fewer ECGs met an ST score of 6 mm when measured at the J point (70% vs. 88%).",
            "output": [
                "Does sT segment elevation differ depending on the method of measurement?"
            ]
        },
        {
            "id": "task847-8ef7d47f85df490f9a1303c2a125af3d",
            "input": "Increased blood flow velocity in the contralateral vertebral artery (VA) is a common finding in subclavian steal syndrome, but its clinical relevance is not known. The aim of this study was to investigate whether the degree of velocity increase in the contralateral VA correlated with the severity of the steal.', 'In a retrospective study of 62 patients with subclavian steal phenomenon and 62 sex- and age-matched controls, we analyzed the peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV), resistance index (RI), and pulsatility index (PI) of the Doppler spectrum of the VA contralateral to the subclavian steal phenomenon. Clinical information including sex, age, comorbidities and Doppler data were recorded from the sonography registration form.', 'In patients with subclavian steal syndrome, Doppler spectral analysis showed a complete reversal of flow in the VA in 29 patients (group A) and an alternating flow in 33 patients (group B). The PSV, MV, RI, and PI of the contralateral VA of patients from both groups were higher than in controls (p < 0.01 for both comparisons). The PSV, EDV, and MV in the contralateral VA were higher in patients with reversed flow compared with those with alternating flow (p < 0.05). Comparisons of clinical symptoms and comorbidities between the two groups did not yield significant findings.",
            "output": [
                "Do hemodynamic effects of subclavian steal phenomenon on contralateral vertebral artery?"
            ]
        },
        {
            "id": "task847-2be87e57ac6d461d936412c23137f9f4",
            "input": "Hypospadias is a common male congenital urethral malformation, defined as the displacement of the urethral meatus ventrally from the tip of the glans penis. The importance of androgen receptor in male external genitalia development has been well recognized. Recently, the presence of active estrogen receptors (ER) in the developing male external genitalia has also been demonstrated. There are two isoforms of the human estrogen receptor, ESR1 and ESR2, which occur, with distinct tissue and cell patterns of expression. We hypothesized that modifications in these nuclear receptors' genes could lead to hypospadias.\", 'We screened 60 boys with hypospadias for mutations in the coding regions of ESR1 and ESR2 genes, by denaturing high-performance liquid chromatography and automated sequence analysis. We also genotyped the CA repeat polymorphism in ESR2 and the TA repeat polymorphism in ESR1.', 'The CA repeat polymorphism in ESR2 is prolonged in hypospadias patients compared to controls (p < 0.05). Prolongation of this CA repeat polymorphism has previously been associated with lower levels of testosterone. Six patients presented the genetic variant 2681-4A > G (rs944050) in the heterozygous form in ESR2, which was a significantly higher frequency than in the control population (p < 0.05). One of these patients also presented a 266_267insC in exon 1 of ESR2, which is also a known single nucleotide polymorphism (SNP; rs3832949). In ESR1, no significant gene alteration was found to be associated with hypospadias.",
            "output": [
                "Are polymorphisms of estrogen receptor beta gene associated with hypospadias?"
            ]
        },
        {
            "id": "task847-5df1f3ab53184b6c98d17491eeba17d5",
            "input": "Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes by assessing expression of the receptor and pharmacological effects on collagen type II degradation under ex vivo and in vivo conditions.', 'Localization of the calcitonin receptor on articular chondrocytes was investigated by immunohistochemistry, and the expression by reverse transcriptase polymerase chain reaction (RT-PCR). In bovine articular cartilage explants, cartilage degradation was investigated by release of C-terminal telopeptides of collagen type II (CTX-II), induced by tumor necrosis factor-alpha (TNF-alpha) [20 ng/ml] and oncostatin M (OSM) [10 ng/ml], with salmon calcitonin [0.0001-1 microM]. In vivo, cartilage degradation was investigated in ovariectomized (OVX) rats administered with oral calcitonin [2 mg/kg calcitonin] for 9 weeks.', 'The calcitonin receptor was identified in articular chondrocytes by immunohistochemistry and RT-PCR. Calcitonin concentration-dependently increased cAMP levels in isolated chondrocytes. Explants cultured with TNF-alpha and OSM showed a 100-fold increase in CTX-II release compared to vehicle-treated controls (P<0.001). The degradation of type II collagen in these explants was concentration-dependently inhibited by calcitonin, 65% protection at 10 nM calcitonin (P<0.01). TNF-alpha and OSM induced a pronounced increase in matrix metalloproteinase (MMP) activity, which was strongly inhibited by calcitonin. In vivo, administration of salmon calcitonin to OVX rats resulted in significant (P<0.001) decrease in CTX-II levels.",
            "output": [
                "Does calcitonin directly attenuate collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes?"
            ]
        },
        {
            "id": "task847-028b1ddca6794cd78028dc311261ef6a",
            "input": "Ischemic postconditioning protects the reperfused heart from infarction, and this protection is dependent on the occupancy of adenosine receptors. We further explored the role of adenosine receptors in this salvage.', 'In situ rabbit hearts underwent 30 min of regional ischemia and 3 h of reperfusion, and postconditioning was effected with four cycles of 30-s reperfusion/30-s coronary artery occlusion at the end of ischemia.', \"Postconditioning reduced infarct size from 40.2+/-3.4% of the risk zone in untreated hearts to 15.5+/-2.5%. Protection by postconditioning was blocked by either the non-selective adenosine receptor blocker 8-p-(sulfophenyl)theophylline or the A2b-selective antagonist MRS 1754, injected intravenously 5 min before reperfusion. The protein kinase C (PKC) antagonist chelerythrine also aborted postconditioning's salvage, indicating a PKC-dependent mechanism. Neither the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine nor the A2a-selective antagonist 8-(13-chlorostyryl)caffeine had an effect on protection. The non-selective but A2b-potent adenosine agonist 5'-(N-ethylcarboxamido)adenosine (NECA) infused from 5 min before to 1h after reperfusion mimicked postconditioning's effect on infarct size (17.2+/-2.7% infarction) and MRS 1754 blocked the NECA-induced cardioprotection, confirming that A2b activation was protective. The PKC activator phorbol 12-myristate 13-acetate delivered just before reperfusion also duplicated the protective effect of postconditioning (16.3+/-4.1% infarction), and co-administration of the PKC antagonist chelerythrine aborted PMA's protection, confirming that the protection was the result of PKC activation. NECA's protective effect was not affected by chelerythrine, but rather MRS 1754 blocked PMA's salutary effect (42.8+/-1.0% infarction), suggesting that the A2b receptor's effect is under control of PKC. Finally, wortmannin, a blocker of phosphatidylinositol 3-kinase, also abrogated protection by PMA.",
            "output": [
                "Does postconditioning protect rabbit hearts through a protein kinase C-adenosine A2b receptor cascade?"
            ]
        },
        {
            "id": "task847-ada2bd6de6734bb398e5cfb593930798",
            "input": "We measured the effect of two weight adjusted i.v. doses (0.2 mg per 70 kg and 0.4 mg per 70 kg) of the potent opioid buprenorphine on analgesia and respiratory depression in healthy volunteers. The aim of the study was to compare buprenorphine's behaviour with respect to the occurrence of ceiling (or apparent maximum) in these typical micro-opioid protein-(MOP) receptor effects.\", 'Ten subjects (5 males) received 0.2 mg per 70 kg, 10 others (5 males) 0.4 mg per 70 kg i.v. buprenorphine. Steady-state inspired minute ventilation at a fixed end-tidal Pco(2) of 7 kPa was measured before drug infusion and at regular intervals after drug infusion. Experimental pain was induced using transcutaneous electrical stimulation and a gradually increasing current. Pain tolerance was measured at regular intervals before and after drug infusion. The studies lasted 8 h.', 'After infusion of the drug ventilation showed a rapid decline and reached peak depression between 150 and 180 min after drug administration. This effect was dose-independent with respect to timing and magnitude. At peak respiratory depression minute ventilation was 13.1 (sd 1.8) litre min(-1) in the 0.2 mg group vs 12.0 (sd 1.3) litre min(-1) in the 0.4 mg group (n.s.). At buprenorphine 0.2 mg a small short-lived analgesic effect was observed with a maximum increase in pain tolerance current of 6.7 (sd 2.8) mA occurring at 75 min after drug administration. Peak analgesic effect was 29% above baseline current. In contrast, buprenorphine 0.4 mg caused a large and long-lived analgesic effect with a maximum increase in pain tolerance current of 23.8 (sd 7.4) mA occurring at 130 min after drug administration. Peak analgesic effect was 160% above baseline current (0.4 vs 0.2 mg, P<0.01).",
            "output": [
                "Does buprenorphine induce ceiling in respiratory depression but not in analgesia?"
            ]
        },
        {
            "id": "task847-19c4e0ac68e24fbf8f245b789f1731af",
            "input": "Despite improvement in the management of severe necrotizing pancreatitis, mortality remains high. Today, no specific treatment exists. Inflammatory cascades and microcirculatory disturbances play a key role in the pathogenesis of acute pancreatitis. The aim of the present study was to evaluate the effects of inosine, an immunomodulatory substance, on the severity of experimental necrotizing pancreatitis.', 'Severe necrotizing pancreatitis was induced in rats. Treatment groups received inosine either prophylactically or therapeutically. Pancreatic injury was evaluated by microcirculatory assessment and histology.', 'Prophylactic inosine significantly attenuated pancreatic microcirculatory disturbances and morphologic injury in necrotizing pancreatitis. However, inosine treatment did not have any beneficial effects when applied therapeutically several hours after onset of the disease.",
            "output": [
                "Does inosine reduce microcirculatory disturbance and inflammatory organ damage in experimental acute pancreatitis in rats?"
            ]
        },
        {
            "id": "task847-c19fab4cbb0746c8b5103308abcb1cf2",
            "input": "To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis.', 'Mice had cerulein administration to induce acute pancreatitis and were pretreated with either anti-mouse neutrophil serum or gadolinium chloride (GdCl3) to prevent Kupffer cell activation, or both treatments. Injury was assessed in pancreas and lungs. Myeloperoxidases (MPO) assessed neutrophil infiltration. Interleukin-6 (IL-6) and IL-10 were measured in serum, pancreas, lungs and liver.', 'In mice with acute pancreatitis, neutrophil depletion reduced the severity of pancreatitis and pancreatitis-associated lung injury. Kupffer cell inactivation by GdCl3 had less protective effect, although IL-6 and IL-10 concentrations were significantly decreased. The protective treatment brought by neutrophil depletion was not enhanced by Kupffer cell inactivation and both treatments did not combine their protective effects.",
            "output": [
                "Does neutrophil depletion -- but not prevention of Kupffer cell activation -- decrease the severity of cerulein-induced acute pancreatitis?"
            ]
        },
        {
            "id": "task847-88b7a13828764e12b353db6a87b49ff7",
            "input": "2-Methoxyestradiol (2ME2), a natural endogenous product of estradiol (E2) metabolism, has been shown to be a selective apoptotic agent for cancer cells but not for normal cells. In this study, we determined that 2ME2 counteracts E2-stimulated cell growth and induces apoptosis in ovarian carcinoma cells. In addition, we demonstrate that 2ME2 induces apoptosis via p38 and phospho-Bcl2 pathway.', '2ME2 and/or E2 were administered to the OVCAR-3 (human ovarian cancer) cell line. Cell growth inhibition was analyzed by [3H] Thymidine incorporation assay and DNA fluorometric assay. Cell apoptosis was tested by DNA fragmentation analysis and FACS. The signaling pathway was determined by a series of biochemical assays.', '2ME2 inhibited estradiol-stimulated cell growth and induced apoptosis in an ovarian carcinoma cell line. MAPK and p38, but not JNK, were found to be critical mediators in this process. Expression of a dominant negative mutant of p38 kinase or p38 specific inhibitor, SB 203580, almost completely blocked the process. Furthermore, Bcl-2 phosphorylation was required for 2ME2-induced effects.",
            "output": [
                "Is p38 Mitogen-activated protein kinases required for counteraction of 2-methoxyestradiol to estradiol-stimulated cell proliferation and induction of apoptosis in ovarian carcinoma cells via phosphorylation Bcl-2?"
            ]
        },
        {
            "id": "task847-0dbcd1a207a646e98d7429d6a215cdd1",
            "input": "Sleep apnoea, which constitutes a major social problem because of its high prevalence and its emerging association with cardiovascular morbidity and mortality, is known to affect autonomic nervous system activity. We assessed the hypothesis that treatment of sleep apnoea patients with continuous positive airway pressure (CPAP) alters the indices of heart rate variability (HRV) that reflect sympathetic and parasympathetic autonomic nervous system activity.', 'We studied 26 patients (18 men, aged 49.2 +/- 7.6 years) with obstructive sleep apnoea-hypopnoea syndrome. In all patients, a 24-hour Holter recording was obtained one week before initiation of CPAP treatment and another one two months later. From these recordings we assessed the time domain indices of HRV (pNN50, rMSSD, SDNN, SDANN, SD) during the day (08:00-23:00) and during the night hours (23:00-08:00) as well as their post-treatment changes. The same HRV indices were also assessed in a group of 19 age and sex matched controls, without sleep apnoea.', 'No significant differences in the HRV indices were observed during the daytime hours, while during the night both pNN50 and rMSSD were significantly higher in patients compared to controls (19.5 +/- 12.5 vs. 13.8 +/- 9.7, p=0.001, for pNN50 and 54.7 +/- 23.1 vs. 44.0 +/- 15.9, p=0.001, for rMSSD, for patients and controls respectively). No such differences were observed in any of the monitored indices following CPAP treatment.",
            "output": [
                "Does continuous positive airway pressure therapy lower vagal tone in patients with obstructive sleep apnoea-hypopnoea syndrome?"
            ]
        },
        {
            "id": "task847-8cd9071eb3e94158bcb3eb5485c34463",
            "input": "The tumor suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose of this study was to investigate the possible association of TSLC1/IGSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC.', 'The promoter methylation of TSLC1/IGSF4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single-strand conformation polymorphism (SSCP) coupled with bisulfite sequencing.', 'The TSLC1/IGSF4 promoter was methylated in 45 (44%) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43%), squamous cell carcinoma (14 of 26, 54%), adenosquamous carcinoma (1 of 2, 50%), and large cell carcinoma (1 of 7, 14%). The incidence of methylation in tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index > or = 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack-years smoked (P = .034) and cigarettes per day (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease-free survival (P = .049), providing an independent prognostic factor (P = .038) in adenocarcinoma patients.",
            "output": [
                "Is hypermethylation of the TSLC1/IGSF4 promoter associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma?"
            ]
        },
        {
            "id": "task847-afb453304c234d2699d7c0f332ef588b",
            "input": "In uterine cervical cancer, certain oncogenic HPV types are considered as key etiologic factor. But the progression of HPV associated cervical precancerous lesions depends on many other factors such as oncogenes, immune system, anti-viral factors etc. This study is therefore focused on the effect of an important dietary anti-viral factor called All Trans Retinoic Acid (ATRA) on the development of HPV associated cervical cancer as it is found higher in poor socioeconomic people.', 'We analyzed a total population of 130 including control subjects who have no complaints of uterine cervical lesions and the HPV-6/11, 16/18 infected cases of low grade squamous intraepithelial lesions [SIL], high grade squamous intraepithelial lesions [HSIL], and invasive cancers, for serum ATRA level. This study also focused to find out the association of serum ATRA level with the proliferation status in terms of proliferating cell nuclear antigen (PCNA) expression as it is an anti-proliferation agent and with the grades of cervical lesions, using SPSS statistical package.', \"The results showed a highly significant negative association for serum ATRA level with different stages of cervical lesions (F = 3.305; P = 0.000) by one-way ANOVA and with intensity of PCNA expression (r = -0.825; P < 0.01) by Pearson's correlation test. A highly significant association was observed for the PCNA expression with the grades of cervical lesions too (F = 37.89; P = 0.000). Further, we found from our data that all the invasive cancer cases were infected with HPV-16/18 and none with HPV-6/11. Hence, we analyzed the association of serum ATRA level with HPV-16/18 infected preinvasive cases in developing invasiveness, by Fisher's Exact Test, using Graph Pad Prism as shown in Table 1. The results show an odds ratio (OR) of 36.93 and a relative risk (RR) of 4.99 with an 95% interval being 2.896 to 8.603, which is significant at the level of P = 0.0001 for the reduced [<0.6 mug/ml] serum ATRA level in developing invasive cancer in HPV-16/18 infected preinvasive cases.",
            "output": [
                "Is hPV-induced carcinogenesis of the uterine cervix associated with reduced serum ATRA level?"
            ]
        },
        {
            "id": "task847-7da33c8139d34024914e2a7781099611",
            "input": "Patients with bradycardia can have severe tachyarrhythmias but it is unclear whether bradycardia alone can induce arrhythmias or whether an additional substrate is necessary. While several animal models of ventricular tachycardia (VT) exist, no model has been reported to mimic the clinical condition of spontaneous VT and sudden cardiac death (SCD) in the presence of bradycardia and chronic myocardial infarction (MI) in large animals without manipulation of the autonomic nervous system. We tested the hypothesis that MI and bradycardia cause more spontaneous sustained VT than does bradycardia alone.', 'Sheep (42-56 kg) underwent atrioventricular (AV) node catheter ablation alone (n = 5) or AV node ablation and 150 minutes of angioplasty balloon occlusion of the left anterior descending coronary artery (n = 9). An implantable cardioverter defibrillator delivered rescue shocks and demand pacing at 90 beats per minute for the first week and at 40 beats per minute thereafter. Electrograms were continuously radiotelemetered and recorded for 6 weeks. Acute post-MI VT disappeared by day 4. The sudden bradycardia on day 8 triggered numerous premature ventricular contractions (PVCs) and episodes of sustained VT lasting >30 seconds during the next 5 weeks. There were 43 episodes of sustained VT and no spontaneous ventricular fibrillation (VF) with bradycardia alone. However, in the presence of both MI and bradycardia there were 970 episodes of VT/VF (P < 0.05) and three deaths at days 13, 15, and 34. The average 24-hour count of PVCs was similar at day 7 between the two groups but by days 11 and 40, the PVC counts were 35 times and 4 times greater, respectively, in the presence of bradycardia and chronic MI compared to bradycardia alone. No significant difference in the incidence of PVCs was detected because of large individual variation between the two groups (P = 0.21). A high PVC count did not appear to predict SCD.",
            "output": [
                "Is chronic myocardial infarction a substrate for bradycardia-induced spontaneous tachyarrhythmias and sudden death in conscious animals?"
            ]
        },
        {
            "id": "task847-1a6d68822efc400f8596b2922e79e235",
            "input": "Cardiac resynchronization therapy (CRT) by simultaneous biventricular pacing is now widely accepted as a new therapeutic option for patients with severe congestive heart failure (CHF). Recent studies have shown comparable hemodynamic benefits of left ventricular (LV) pacing alone. The clinical usefulness of CRT, however, might be compromised by potential exaggeration of arrhythmogenic substrates through a modification of ventricular repolarization.', 'We compared ECG parameters during sinus rhythm (SR), atrioventricular synchronous pacing at the right ventricular apex (RV(end)P), at LV epicardium (LV(epi)P), and at both sites (BiVP) in acute homodynamic studies of 14 CHF patients scheduled for CRT (QRS duration = 144 +/- 23 msec, LVEF = 27 +/- 10%). The maximum rate of increase in LV pressure (LVdp/dt(max)) was decreased significantly during RV(end)P, whereas it was increased similarly during LV(epi)P and BiVP compared with SR. QTc was increased during RV(end)P (by 10.2%) and LV(epi)P (by 26.1%). QTc dispersion (QTc(max)-QTc(min) in the six precordial leads) was also increased during LV(epi)P (by 66.5%). These parameters were unaffected during BiVP. JTc was unchanged, and the interval from the peak to the end of the T wave (Tc(peak-end)) was increased slightly (by 19.3%) during RV(end)P. Both JTc and Tc(peak-end) were increased dramatically during LV(epi)P (by 18.2% and 55.4%, respectively), but increased only modestly during BiVP (by 6.6% and 15.8%, respectively).",
            "output": [
                "Does biventricular pacing have an advantage over left ventricular epicardial pacing alone to minimize proarrhythmic perturbation of repolarization?"
            ]
        },
        {
            "id": "task847-c5b2031e40424170b516096a42232942",
            "input": "Bone morphogenetic proteins (BMPs) have the potential to improve incorporation of allograft bone in revision surgery. This could result in improved fixation and graft incorporation.', 'We evaluated the effect of mixing OP-1 (BMP-7) with morselized allograft in hip revisions. In a case-control study, 20 acetabular revisions (10 in the study group, 10 controls) and 41 femoral revisions (11 in study group, 30 controls) were done using impaction allografting. The migration of the cups and stems was studied with radiostereometric analysis (RSA) for up to 5 years. Changes of bone mineral density around the femoral component were measured with dual energy X-ray adsorptiometry for 2 years. Bone remodeling and the extent of radiolucent lines were evaluated on conventional radiographs after 5 years. The clinical results were documented using Harris hip score.', 'In the cup study, there was no significant difference in implant migration between the study and control groups. 4 sockets in the study group were classified as radiographically loose after 5 years and 2 of them were revised after 5 years. After 2 years, the stems in the study group showed slightly increased posterior tilt (0.3 degrees , p = 0.03). 1 stem in the study group loosened and was revised during the third year of observation.",
            "output": [
                "Does mixing bone graft with OP-1 improve cup or stem fixation in revision surgery of the hip : 5-year follow-up of 10 acetabular and 11 femoral study cases and 40 control cases?"
            ]
        },
        {
            "id": "task847-fa8ff6d702414685aad94b4710cd059d",
            "input": "Controversy exists as to whether polyethylene (PE) penetration of hip prostheses is underestimated when the measurements are made on radiographs obtained in supine position as compared to weight-bearing position.', 'We examined 111 patients by radiostereometric analysis (RSA) in the supine and weight-bearing positions.', 'The mean 3-D penetration was 0.68 mm (SD 0.58, range 0.04-3.05) for the supine position and 0.70 mm (SD 0.57, range 0.08-3.01) for the weight-bearing position. The correlation between supine and weight-bearing examinations was 0.99 (p < 0.001). The degree of penetration made no difference. There was no statistically significant difference as to whether the first examination was performed early, i.e. after 3 months, or after 12 months (p = 0.7).",
            "output": [
                "Are weight bearing radiographs necessary for measurement of polyethylene penetration in total hip prostheses : a radiostereometric study of 111 patients examined in weight-bearing and supine position?"
            ]
        },
        {
            "id": "task847-9933aec5023b403ab347ada2045987b7",
            "input": "Carotenoids may reduce the risk for diabetes mellitus, but little is known about the association of insulin resistance with serum carotenoids in non-diabetic subjects. This study aimed to investigate whether the homeostasis model assessment-insulin resistance (HOMA-IR) index would be lower in the presence of high serum carotenoid concentrations in non-diabetic subjects.', 'A total of 812 subjects (256 males and 556 females) who had received health examinations in 2003 participated in the study. The associations of the serum-carotenoid concentrations and HOMA-IR were evaluated cross-sectionally. The multivariate-adjusted geometric means of HOMA-IR by the tertiles of the serum carotenoid concentration were calculated after adjusting for age, body mass index, systolic blood pressure, total cholesterol, triacylglycerols, current tobacco use, regular alcohol intake, exercise habits and total energy intake. Associations among high HOMA-IR (3.0+mUxmmol/L2) across tertiles of serum carotenoid concentration were assessed by tests for logistic regression analysis.', 'In male subjects, the multivariate adjusted geometric mean of HOMA-IR was inversely associated with the serum beta-cryptoxanthin concentrations. In female subjects, an inverse association of the serum carotenoid concentration and HOMA-IR was observed in lycopene, beta-cryptoxanthin, and zeaxanthin. The confounding factor-adjusted odds ratios (OR) for high HOMA-IR on the highest tertiles of serum alpha-carotene, beta-carotene, beta-cryptoxanthin, and zeaxanthin were 0.18 [95% confidence interval (CI): 0.06-0.52], 0.22 (95% CI: 0.07-0.67), 0.34 (95% CI: 0.12-0.96), and 0.30 (95% CI: 0.11-0.79), respectively, in male subjects. On the other hand, in female subjects, the adjusted OR for high HOMA-IR on the highest tertiles of serum lycopene and beta-cryptoxanthin were 0.39 (95% CI: 0.21-0.73) and 0.51 (95% CI: 0.28-0.95), respectively.",
            "output": [
                "Is the homeostasis model assessment-insulin resistance index inversely associated with serum carotenoids in non-diabetic subjects?"
            ]
        },
        {
            "id": "task847-ffb3811358364e19ba02c4c1f7710b95",
            "input": "To identify the genetic basis of recessive inheritance of high hyperopia and Leber congenital amaurosis (LCA) in a family of Middle Eastern origin.', 'The patients were examined using standard ophthalmic techniques. DNA samples were obtained and genetic linkage was carried out using polymorphic markers flanking the known genes and loci for LCA. Exons were amplified and sequenced.', 'All four members of this family affected by LCA showed high to extreme hyperopia, with average spherical refractive errors ranging from +5.00 to +10.00. Linkage was obtained to 1q31.3 with a maximal LOD score of 5.20 and a mutation found in exon 9 of the CRB1 gene, causing a G1103R substitution at a highly conserved site in the protein. CRB1 is a vertebrate homolog of the Drosophila crumbs gene, which is required for photoreceptor morphogenesis, and has been associated with either retinitis pigmentosa (RP) or LCA. This sequence variant has previously been reported as a compound heterozygote in one sporadic LCA patient.",
            "output": [
                "Is a G1103R mutation in CRB1 co-inherited with high hyperopia and Leber congenital amaurosis?"
            ]
        },
        {
            "id": "task847-d9524628ca534e96a0cac9840107b37d",
            "input": "To study biofilm production and to detect icaAD, atlE and aap genes in 137 isolates of methicillin-resistant Staphylococcus epidermidis (MRSE) obtained from healthy individuals from the community (35 isolates), from hospitalized patients at the Ant\u00f4nio Pedro University Hospital (25 isolates) and from individuals from a home-care system (HCS; 77 isolates).', 'Biofilm production was determined in vitro using polystyrene inert surfaces. icaAD, atlE and aap genes were detected using PCR. Hybridization experiments were also carried out to confirm some PCR results. Antimicrobial susceptibility testing was carried out using the NCCLS methods.', 'Although many of the commensal MRSE isolates produced biofilms, the percentage of biofilm producers was significantly higher (P = 0.0107) among hospital isolates (76%) than among isolates from the community (60%) and from the HCS (57%). An association was observed between multiresistance and biofilm production for isolates obtained from healthy individuals from the community and from household contacts from the HCS (P < 0.0001). The concomitant presence of the ica operon and atlE and aap genes was associated with the strong biofilm-producer phenotype (P < 0.0001).",
            "output": [
                "Are commensal isolates of methicillin-resistant Staphylococcus epidermidis also well equipped to produce biofilm on polystyrene surfaces?"
            ]
        },
        {
            "id": "task847-1bae97b2e51a4d06b40ae94ce0ec6262",
            "input": "In the present report, we analyze the efficacy of the sanitary regulations to kill the Anisakis simplex larvae (As L3) (heat or freeze) to avoid the gastrointestinal alterations that it provokes. We studied the effects on intestinal contractility (muscular tone, amplitude, and frequency of the twitches and cholinergic and alpha-adrenergic stimulus) of As L3, their crude extracts (CE) and excretory-secretory products (ESP), untreated or heated (60 degrees C for 15 min) or frozen (-20 degrees C for 24 h) using rat ileum and an isometric system. Carbachol and noradrenaline have been used as cholinergic and alpha-adrenergic stimulus, respectively. We determined that viable As L3, their untreated CE and ESP, as well as all their frozen counterparts, altered the intestinal contractile activity and its autonomic control. In contrast, heated As L3, CE, and ESP were incapable of provoking any change in rat ileum motility, suggesting an inhibitory effect by the heating procedure.",
            "output": [
                "Does freezing infective-stage larvae from Anisakis simplex and their produce at -20 degrees C for 24 h prevent the occurrence of autonomic imbalance in rat ileum?"
            ]
        },
        {
            "id": "task847-6a673d3b4c47403bbe5316aa79eb1962",
            "input": "Insight into clinical response to platinum-based chemotherapy (PBC) in non-small-cell lung cancer (NSCLC).', 'Matched tumor and nontumor lung tissues from PBC-treated NSCLC patients (four nonresponders and four responders) and tumor tissue from an independent test set (four nonresponders and four responders), were profiled using microarrays. Lysosomal protease inhibitors SerpinB3 and cystatin C were highly correlated with clinical response and were further evaluated by immunohistochemistry in PBC-treated patients (36 prechemotherapy and 13 postchemotherapy). Investigation of the pathogenic and prognostic significance of SerpinB3 was performed in 251 primary tumors, with 64 regional lymph node pairs, from chemotherapy-na\u00efve NSCLC patients using immunohistochemistry.', 'Bioinformatic analyses of gene expression in the training set identified a gene set (n = 17) that separated all patients in the training and test sets (n = 16) according to response in hierarchical clustering. Transcriptome profiling revealed that SerpinB3 mRNA was highly correlated with degree of response (r = -0.978; P < .0001) and was a clear outlier (nonresponders:responders > 50-fold). SerpinB3 protein expression was correlated with clinical response in PBC-treated NSCLC patients (P = .045). Expression of SerpinB3 and cystatin C, relative to the target, protease cathepsin B, was independently predictive of response (odds ratio, 17.8; 95% CI, 2.0 to 162.4; P = .01), with an accuracy of 72%. High SerpinB3 expression levels, invariably associated with chemoresistance, had contrasting prognostic impact in untreated squamous cell carcinomas (hazard ratio [HR], 0.43; 95% CI, 0.18 to 0.93) or adenocarcinomas (HR, 2.09; 95% CI, 1.03 to 4.72).",
            "output": [
                "Does tumor transcriptome reveal the predictive and prognostic impact of lysosomal protease inhibitors in non-small-cell lung cancer?"
            ]
        },
        {
            "id": "task847-c75354c8146247c2845504c80351e5b2",
            "input": "This study was conducted to gain insight into the relationship between expression profiles and underlying genetic changes, which are known to be important for the pathogenesis of lung cancers.', 'Expression profiles of 18,175 unique genes and three major targets for genetic changes, p53, epidermal growth factor receptor (EGFR), and K-ras, were investigated in 149 patients with non-small-cell lung cancer, including 90 patients with adenocarcinoma to determine their relationships with various clinicopathologic features and Gene Ontology (GO) terms.', 'This study successfully established a basis for expression profile-defined classification, which can classify adenocarcinomas into two major types, terminal respiratory unit (TRU) type and non-TRU type. Our GO term-based identifier of particular biologic processes, molecular functions, and cellular compartments clearly showed characteristic retention of normal peripheral lung features in TRU type, in sharp contrast to the significant association of non-TRU type with cell cycling and proliferation-related features. While significantly higher frequency of EGFR mutation was observed in TRU type, we found that the presence of EGFR mutations was a significant predictor of shorter postoperative survival for TRU type, independent of disease stage. We were also able to identify a set of genes in vivo with significant upregulation in the presence of EGFR mutations.",
            "output": [
                "Does expression profile-defined classification of lung adenocarcinoma show close relationship with underlying major genetic changes and clinicopathologic behaviors?"
            ]
        },
        {
            "id": "task847-2ba5e3ac81aa45c895b355a1de287e7e",
            "input": "Hepatic steatosis and nonalcoholic steatohepatitis (NASH) have been increasingly implicated in the genesis of hepatic fibrosis and cirrhosis. However, no consensus exists about whether weight reduction may reverse this process.', 'To assess the effect of Roux-en-Y gastric bypass (RYGBP) on the histological evolution of NASH diagnosed in 64 patients by routine liver biopsy (\"first\" biopsy) performed during surgery, we performed a \"second\" biopsy after 23.5 +/- 8.4 months in 16 patients (14 female, 2 male).', 'From the first to the second biopsy, BMI decreased from 53.4 +/- 8.8 kg/m2 to 31.1 +/- 4.7 kg/m2, arterial hypertension decreased from 75% to 43.8%, and type 2 diabetes decreased from 43.8% to zero. On the first biopsy, nonalcoholic fatty liver disease (NAFLD) type 3 was observed in 12 patients (75%) and type 4 in 4 (25%). The second biopsy revealed complete regression of NAFLD in 15 patients (93.7%) and only 1 (6.3%) had NAFLD type 1 (mild steatosis without inflammation). Complete regression of necroinflammatory activity was observed in all patients. Among the 4 patients presenting fibrosis in the first biopsy, complete remission was observed in 1 and improvement in 1. Two continued to show the same degree of fibrosis without evidence of disease activity. No worsening of steatosis, necroinflammatory activity or fibrosis was observed in any of the patients, and none progressed to cirrhosis.",
            "output": [
                "Does roux-en-Y gastric bypass improve the nonalcoholic steatohepatitis ( NASH ) of morbid obesity?"
            ]
        },
        {
            "id": "task847-bf8596adb7fa4073a2f42152c4b7bc59",
            "input": "Chronic lymphocytic leukemia (CLL) is an incurable disease with a highly variable clinical course. IgV(H) mutational status, chromosomal aberrations, CD38 expression and ZAP-70 expression are prognostic markers in CLL, however, they are not exclusively confined to this disease. We recently identified a novel CLL-specific gene (CLL upregulated gene1, CLLU1) that is exclusively upregulated in CLL cells. Here we describe our evaluation of the prognostic significance of CLLU1 in CLL.', 'A cohort of 59 previously untreated CLL patients was studied. We determined the expression levels of two CLLU1 transcripts, cDNA1 and CDS, by quantitative RT-PCR. The relation between CLLU1 expression and time to therapy, overall survival and presence or absence of ZAP-70, CD38, chromosomal aberrations or IgV(H) mutations in the 59 patients was analyzed.', 'Analyzed as a continuous, quantitative parameter CLLU1 levels significantly predicted time from diagnosis to initiation of therapy (P < or = 0.0003) Analyzed as a categorical parameter, by segregation of the patients into groups with cDNA1 or CDS expression above or below the median, the CLLU1 levels significantly predicted time from diagnosis to initiation of therapy (P = 0.001) and predicted overall survival with borderline significance (P < or = 0.05). Patient stratification according to clinical stage, cytogenetics, IgV(H) mutational status, ZAP-70 and CD38, demonstrated significantly increased CLLU1 expression in all investigated CLL poor risk groups. CLLU1 expression levels contributed additional prognostic information to ZAP-70-positive patients.",
            "output": [
                "Do cLLU1 expression levels predict time to initiation of therapy and overall survival in chronic lymphocytic leukemia?"
            ]
        },
        {
            "id": "task847-dce8e552a60846ffb765eaad5eeedf6f",
            "input": "The present study examines the differences in gastrointestinal hormone production at 3 different reconstruction types after total gastrectomy.', 'Total gastrectomy causes significant weight loss, mainly due to a reduced caloric intake probably because of a lack of initiative to eat or early satiety during meals. Behind this phenomenon a disturbed gastrointestinal hormone production can be presumed.', 'Patients participating in a randomized study were recruited for the clinical experiment. Seven patients with simple Roux-en-Y reconstruction, 11 with aboral pouch (AP) construction, and 10 with aboral pouch with preserved duodenal passage (APwPDP) reconstruction, as well as 6 healthy volunteers were examined. Blood samples were taken 5 minutes before and 15, 30, and 60 minutes after ingestion of a liquid test meal. Plasma concentrations for insulin, cholecystokinin, and somatostatin were determined by radioimmunoassay analysis.', 'Postprandial hyperglycemia was observed in patients after total gastrectomy most prominently in groups with duodenal exclusion (Roux-en-Y and AP) compared with healthy controls. Postprandial insulin curves reached significantly higher levels in all operated groups compared with controls, however, with no difference according to reconstruction type. Significantly higher cholecystokinin levels and higher integrated production of cholecystokinin were observed in Roux-en-Y and AP groups compared with APwPDP and control. Postprandial somatostatin levels were significantly different between the 4 groups, and highest levels and integrated secretions were reached in AP group, lowest in APwPDP and normal groups.",
            "output": [
                "Is postprandial gastrointestinal hormone production different , depending on the type of reconstruction following total gastrectomy?"
            ]
        },
        {
            "id": "task847-676c7dcd75594b6c9717fda530cd6534",
            "input": "One of the factors leading to an invasive phenotype is the nm23 family of metastases-associated genes. Of the six known members, nm23-H1 is the most frequently studied potential anti-metastatic gene in cervical cancer. However, the possible molecular links to oncogenic human papillomavirus (HPV) are completely unexplored as yet.', 'As a part of the HPV-Pathogen Istituto Superiore di Sanit\u00e0 study, a series of 150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions were examined by immunohistochemical staining for nm23-H1, and tested for HPV by polymerase chain reaction (PCR) with three sets of primers (MY09/11, GP5(+)/GP6(+) and short PCR fragment). Follow-up data were available on all patients with SCC, and 67 CIN lesions were monitored by serial PCR for clearance or persistence of HPV after cone treatment.', 'A linear decrease (p = 0.001) was observed in nm23-H1 expression, starting from CIN1 (85% with normal expression), with the most dramatic down regulation on transition from CIN2 (70% normal) to CIN3 (39%) and further to SCC (25%). Reduced expression was associated with CIN3 or cancer at an odds ratio 8.72 (95% confidence interval 4.13 to 18.41). Nm23-H1 was of no use as a marker of the high-risk human papillomavirus (HR-HPV) type, and it did not predict clearance or persistence of HR-HPV after treatment of CIN. Importantly, nm23-H1 expression was a significant prognostic factor in cervical cancer, reduced expression being associated with lower survival (p = 0.022) in univariate analysis. In the multivariate (Cox) regression model, however, only the International Federation of Gynecology and Obstetrics stage (p = 0.001) and age (p = 0.011) remained independent prognostic predictors.",
            "output": [
                "Is down-regulated nucleoside diphosphate kinase nm23-H1 expression unrelated to high-risk human papillomavirus but associated with progression of cervical intraepithelial neoplasia and unfavourable prognosis in cervical cancer?"
            ]
        },
        {
            "id": "task847-bb00d3e1575345d8aa1da71b7009ee1e",
            "input": "Obstructive sleep apnoea (OSA) is a common and potentially reversible cause of systemic hypertension. The mechanisms whereby OSA leads to hypertension and the effects of treatment on arterial function, however, are not well established. Microvascular arterial endothelial and smooth muscle function was assessed in subjects with OSA before and after treatment with continuous positive airways pressure (CPAP).', 'Ten subjects of mean (SE) age 49 (8) years with at least moderately severe OSA had detailed forearm vascular reactivity studies before and after 3 months of CPAP treatment. The systemic circulation was assessed by measuring brachial artery pressure, flow and resistance responses to intra-arterial infusions of acetylcholine (ACh; an endothelium dependent vasodilator), sodium nitroprusside (SNP; an endothelium independent vasodilator), L-NMMA (a nitric oxide (NO) antagonist), and L-arginine (the substrate for NO).', 'Before CPAP, ACh and SNP infusions increased forearm blood flow in a dose dependent manner (p<0.01). After CPAP, endothelium dependent dilation to ACh was significantly increased (434 (23)% of baseline after CPAP v 278 (20)% before CPAP, p<0.001), whereas SNP induced dilation was unchanged. Resting NO production was higher after CPAP, evidenced by a significantly greater reduction in basal flow by L-NMMA (p=0.05). L-Arginine reversed the effect of L-NMMA in all cases.",
            "output": [
                "Does treatment of obstructive sleep apnoea lead to improved microvascular endothelial function in the systemic circulation?"
            ]
        },
        {
            "id": "task847-d69c6ce936444f8b9977b456e1fd5e6d",
            "input": "We investigated whether patient-controlled epidural analgesia in labor with bupivacaine and fentanyl provides more satisfaction to mothers than intermittent bolus epidural analgesia or patient-controlled epidural analgesia with plain bupivacaine.', 'Ninety mothers with term, uncomplicated pregnancies were randomized to receive intermittent bolus epidural analgesia (bupivacaine + fentanyl), patient-controlled epidural analgesia (bupivacaine + fentanyl), or patient-controlled epidural analgesia (bupivacaine). Pain during labor was evaluated with a visual analog scale. Obstetric and neonatal outcomes were recorded. After delivery, the mothers were given a questionnaire covering the following themes: experience of labor pain, feeling of control, fears and expectations associated with pregnancy/with delivery/with becoming a mother, as well as pain, physical condition and emotions after delivery. To elaborate on these answers, 30 mothers were further randomized to a semistructured interview, in which the same topics were discussed. The main outcome measure was maternal satisfaction.', 'The intermittent bolus epidural analgesia group felt they could influence labor most (p = 0.03), and in the interview they expressed most satisfaction. In this group, the total drug utilization was smallest (bupivacaine: p <0.0001 comparing all groups, fentanyl: p = 0.03 comparing the two fentanyl-receiving groups). No differences in pain occurred. Vomiting (p = 0.04) and pruritus (p <0.0001) were more common or more severe in the groups receiving fentanyl.",
            "output": [
                "Does patient-controlled epidural analgesia in labor always improve maternal satisfaction?"
            ]
        },
        {
            "id": "task847-344b77429bb44007a483513d786f5a46",
            "input": "The haplotypes in the gene vitamin K epoxide reductase complex subunit 1 (VKORC1) have been found to affect warfarin dose response through effects on the formation of reduced-form vitamin K, a cofactor for gamma-carboxylation of vitamin K-dependent proteins, which is involved in the coagulation cascade and has a potential impact on atherosclerosis. We hypothesized that VKORC1-dependent effects on the coagulation cascade and atherosclerosis would contribute to susceptibility for vascular diseases.', \"To test the hypothesis, we studied the association of polymorphisms of VKORC1 with stroke (1811 patients), coronary heart disease (740 patients), and aortic dissection (253 patients) compared with matched controls (n=1811, 740, and 416, respectively). Five common noncoding single-nucleotide polymorphisms of VKORC1 were identified in a natural haplotype block with strong linkage disequilibrium (D'>0.9, r2>0.9), then single-nucleotide polymorphism (SNP) +2255 in the block was selected for the association study. We found that the presence of the C allele of the +2255 locus conferred almost twice the risk of vascular disease (odds ratio [OR] 1.95, 95% confidence interval [CI] .58 to 2.41, P<0.001 for stroke; OR 1.72, 95% CI 1.24 to 2.38, P<0.01 for coronary heart disease; and OR 1.90, 95% CI 1.04 to 3.48, P<0.05 for aortic dissection). We also observed that subjects with the CC and CT genotypes had lower levels of undercarboxylated osteocalcin (a regulator for the bone), probably vascular calcification, and lower levels of protein induced in vitamin K absence or antagonism II (PIVKA-II, a des-gamma-carboxy prothrombin) than those with TT genotypes.",
            "output": [
                "Are vKORC1 haplotypes associated with arterial vascular diseases ( stroke , coronary heart disease , and aortic dissection )?"
            ]
        },
        {
            "id": "task847-fb246b673e284d0890a7f392d5fcadb9",
            "input": "Post-prandial glucose may be a risk factor for cardiovascular disease and chronic diabetic complications. We tested the hypothesis that post-prandial hyperglycaemia is common in type 2 diabetes, even among patients in apparently good glycaemic control, and that simple clinical characteristics identify subsets of diabetic patients with frequent post-prandial hyperglycaemia.', 'Three self-assessed daily blood glucose profiles over a 1-week period, including 18 glucose readings before and 2 h after meals, were obtained from 3,284 unselected outpatients (men 51%; age 63+/-10 years) with non-insulin-treated type 2 diabetes mellitus attending 500 different diabetes clinics operating throughout Italy.', 'A post-prandial blood glucose value >8.89 mmol/l (160 mg/dl) was recorded at least once in 84% of patients, and 81% of patients had at least one Delta glucose > or =2.22 mmol/l (40 mg/dl). Among patients with apparently good metabolic control, 38% had >40% of post-prandial blood glucose readings >8.89 mmol/l (> or =4 of 9 meals in total), and 36% had >40% Delta glucose > or =2.22 mmol/l. In multivariate analysis adjusted for pre-prandial glucose levels, older age, longer duration of diabetes, absence of obesity, hyperlipidaemia and hypertension, as well as treatment with sulfonylureas, were significantly associated with greater glucose excursions after meals.",
            "output": [
                "Does prevalence and correlate of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus?"
            ]
        },
        {
            "id": "task847-1ce4430f8be042edb2698908e34e5590",
            "input": "Adiponectin is a recognized protective risk marker for cardiovascular disease in adults and is associated with an optimal lipid profile. The role of adiponectin at birth is not well understood, and its relationship with the neonatal lipid profile is unknown. Because ethnic disparities in cardiovascular risk have been attributed to low adiponectin and its associated low high-density lipoprotein cholesterol (HDL-C), investigation at birth may help determine the etiology of these risk patterns.', 'Our objective was to investigate the relationship between neonatal adiponectin and lipid profile at birth in two ethnic groups in cord blood.', \"Seventy-four healthy mothers and their newborns of South Asian and White European origin were studied in this cross-sectional study at St. Mary's Hospital, Manchester, United Kingdom.\", 'Serum adiponectin, total cholesterol, HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were measured in umbilical venous blood at birth and in maternal blood collected at 28 wk gestation.', 'Cord adiponectin was significantly inversely associated with cord LDL-C (r = -0.32; P = 0.005) but not HDL-C. In a multiple regression analysis, cord LDL-C remained the most significant association of cord adiponectin (beta = -0.13; P < 0.001). We did not find any significant ethnic differences in cord adiponectin or lipids with the exception of triglycerides, which were significantly lower in South Asian newborns (P < 0.05).",
            "output": [
                "Is adiponectin in umbilical cord blood inversely related to low-density lipoprotein cholesterol but not ethnicity?"
            ]
        },
        {
            "id": "task847-897bcc49d749405ea2f7c93dde74c9ed",
            "input": "To investigate the clinicopathologic factors related with recurrence and prognosis after surgical resection for I stage lower rectal carcinoma.', 'The related clinicopathologic factors for recurrence and prognosis of 166 patients with I stage lower rectal carcinoma after surgical resection were retrospectively analyzed using univariate and multivariate methods.', 'A total of 138 patients with I stage lower rectal carcinoma received radical resection according to the operative rules of total mesorectal excision (TME). Ninety-three patients received abdominoperineal resection (APR) operation, 45 patients received sphincter preserving operation, and 28 patients received local excision. The local recurrence rates were 6.5% (6/93), 2.2% (1/45), 17.9% (5/28), respectively . Histological differentiation and operative procedures were associated with local recurrence. The 5-year survival rates were 91.1% in APR group, 95.5% in sphincter preservation group and 82.6% in local resection group. Univariate analysis revealed that histological differentiation and local recurrence were correlated with prognosis. Multivariate analysis revealed that local recurrence was the most important prognostic factor for I stage lower rectal carcinoma.",
            "output": [
                "Do [ Analysis of recurrence and prognosis after surgical resection for I stage lower rectal carcinoma ]?"
            ]
        },
        {
            "id": "task847-457a68c861744dfdbe9484c87dde4e10",
            "input": "Ventriculo-peritoneal shunting is the most commonly used method for the treatment of paediatric hydrocephalus. The programmable valve with the ability to adjust the opening pressure non-invasively has made it easier to find exactly the right opening pressure for each child and reduce the risk of over- or under-drainage. The aim of this investigation was to study our clinical experience with the adult Codman Hakim programmable valve in children, with reference to complications and economic impact.', 'A seven-year retrospective study of 122 hydrocephalic children (aged from children born prematurely to 15 years old) shunted with the adult Codman Hakim programmable valve was performed.', 'The programmable valve was the first shunt in 76 children and in 14 after prior ventricular drainage. The remaining 46 had different non-programmable systems as their first shunt. The most common reason for changing to a programmable valve was over-drainage. With the programmable valve, catheter-related complications, e.g. proximal (36%) or distal obstructions (30%), were the main reasons for surgical revision. Non-invasive pressure adjustment was performed in 73% of the children. Among the children with the programmable valve as their first shunt, 57 (75%) were adjusted, 12 (21%) had severe symptoms of over-drainage and would have required urgent surgical change of the valve if it had not been adjustable. A resetting of the opening pressure after MRI was found in 38% and accidental resetting occurred in 4%. Programmable valves are about twice as expensive as non-programmable valves. We estimated the increased cost of the valve and compared it with the savings from a reduction in the number of re-operations. The total cost for the programmable valve (as the primary shunt) in our study was less than that for expected re-operations due to over- or under-drainage when using non-programmable valves.",
            "output": [
                "Is the programmable adult Codman Hakim valve useful even in very small children with hydrocephalus . A 7-year retrospective study with special focus on cost/benefit analysis?"
            ]
        },
        {
            "id": "task847-2526eea7df7641aaa7fe0730ad718fe3",
            "input": "The exact role Entamoeba histolytica cysteine proteases play in overcoming the colonic mucus barrier, as a prerequisite to epithelial cell disruption, is not known. Herein, we determined whether E histolytica trophozoites expressing the antisense transcript to cysteine protease 5 (EhCP5) could degrade colonic mucin and destroy epithelial cells.', 'Cysteine protease-deficient amoebae were generated by antisense inhibition of EhCP5, and assayed for proteolytic activity against [(35)S]cysteine-labeled mucin from LS 174T, and HT-29F Cl.16E cells. Recombinant EhCP5 mucinase activity was also assessed. Disruption of an intact mucus barrier and epithelial cell invasion by amoebae were measured using high mucin producing LS 174T and HT-29 Cl.16E monolayers or Chinese hamster ovary (CHO) cells devoid of a mucus barrier.', 'Trophozoites with reduced cysteine protease activity were ineffective at degrading [(35)S]cysteine-labeled colonic mucin compared to wild-type amoebae by >60%. However, bioactive recombinant EhCP5 degraded >45% of purified native mucin, which was specifically inhibited by the cysteine proteinase (CP) inhibitor, E-64. Cysteine protease-deficient trophozoites could not overcome a protective intact mucus barrier and disrupt LS 174T or HT-29F Cl.16 cell monolayers; however, they readily adhere to and disrupt CHO monolayers devoid of a mucus barrier.",
            "output": [
                "Does antisense inhibition of Entamoeba histolytica cysteine proteases inhibit colonic mucus degradation?"
            ]
        },
        {
            "id": "task847-503db382bd2941e0be87985b1f541a9c",
            "input": "Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Effective therapies for liver fibrosis are lacking. Interleukin-10 (IL-10) is a cytokine that downregulates pro-inflammatory responses and has a modulatory effect on hepatic fibrogenesis. The aim of this study was to investigate whether electroporative IL-10 gene therapy has a hepatic fibrolytic effect on mice.', 'Hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) for 10 weeks in mice. The human IL-10 expression plasmid was delivered via electroporation after hepatic fibrosis was established. Histopathology, reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and gelatin zymography were used to investigate the possible mechanisms of action of IL-10.', 'Human IL-10 gene therapy reversed CCl4-induced liver fibrosis in mice. RT-PCR revealed that IL-10 gene therapy attenuated liver TGF-beta1, collagen alpha1, fibronectin, and cell adhesion molecule mRNA upregulation. Following gene transfer, both the activation of alpha-smooth muscle actin and cyclooxygenase-2 were significantly attenuated. Furthermore, IL-10 significantly inhibited matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase (TIMP) activation after CCl4 intoxication.",
            "output": [
                "Does electroporative interleukin-10 gene transfer ameliorate carbon tetrachloride-induced murine liver fibrosis by MMP and TIMP modulation?"
            ]
        },
        {
            "id": "task847-d21da380e80a437f8df4df91a1561b32",
            "input": "To test the hypothesis that statins inhibit leptin-induced hypertrophy in cultured neonatal rat cardiomyocytes.', \"Cultured neonatal rat cardiomyocytes were used to evaluate the effects of simvastatin on leptin-induced hypertrophy. Intracellular reactive oxygen species (ROS) levels were determined by using 2',7'-dichlorofluorescein diacetate (DCF-DA) fluorescence. Total intracellular RNA and cell protein content, which serve as cell proliferative markers, were assayed by using propidium iodide (PI) fluorescence and the Bio-Rad DC protein assay, respectively. The cell surface area, an indicator of cell hypertrophy, was quantified by using Leica image analysis software.\", 'After 72 h treatment, leptin markedly increased RNA levels, cell surface area, and total cell protein levels in cardiomyocytes, which were significantly inhibited by simvastatin or catalase treatment. ROS levels were significantly elevated in cardiomyocytes treated with leptin for 4 h compared with those cells without leptin treatment. The increase in ROS levels in cardiomyocytes induced by leptin was reversed by treatment with simvastatin and catalase.",
            "output": [
                "Does simvastatin inhibit leptin-induced hypertrophy in cultured neonatal rat cardiomyocytes?"
            ]
        },
        {
            "id": "task847-d27dc84232c64077a8aff0966ea65b99",
            "input": "After cloning of the second estrogen receptor, estrogen receptor beta (ERbeta) in 1996, increasing evidence of its importance in prostate cancer development has been obtained. ERbeta is thought to exert an antiproliferative and proapoptotic effect. We examined whether sequence variants in the ERbeta gene are associated with prostate cancer risk.', \"We conducted a large population-based case-control study (CAncer Prostate in Sweden, CAPS) consisting of 1,415 incident cases of prostate cancer and 801 controls. We evaluated 28 single nucleotide polymorphisms (SNP) spanning the entire ERbeta gene from the promoter to the 3'-untranslated region in 94 subjects of the control group. From this, we constructed gene-specific haplotypes and selected four haplotype-tagging SNPs (htSNP: rs2987983, rs1887994, rs1256040, and rs1256062). These four htSNPs were then genotyped in the total study population of 2,216 subjects.\", 'There was a statistically significant difference in allele frequency between cases and controls for one of the typed htSNPs (rs2987983), 27% in cases and 24% in controls (P = 0.03). Unconditional logistics regression showed an odds ratio of 1.22 (95% confidence interval, 1.02-1.46) for men carrying the variant allele TC or CC versus the wild-type TT, and an odds ratio of 1.33 (95% confidence interval, 1.08-1.64) for localized cancer. No association of prostate cancer risk with any of the other SNPs or with any haplotypes were seen.",
            "output": [
                "Is estrogen receptor beta polymorphism associated with prostate cancer risk?"
            ]
        },
        {
            "id": "task847-10641bec8a074060ae2443bb760b3795",
            "input": "To evaluate whether simvastatin influences (i) the intestinal expression of P-glycoprotein (P-gp) and MRP2, and (ii) the disposition of the beta(1)-selective blocker talinolol, a substrate of these transporter proteins.', 'The disposition of talinolol after intravenous (30 mg) and single or repeated oral administration (100 mg daily) was monitored before and after chronic treatment with simvastatin (40 mg daily) in 18 healthy subjects (10 males, eight females, body mass index 19.0-27.0 kg m(-2)) genotyped for ABCB1, ABCC2 and SLCO1B1 polymorphisms. The steady-state pharmacokinetics of simvastatin was evaluated before and after repeated oral talinolol administration. The duodenal expression of ABCB1 and ABCC2 mRNA before and after simvastatin treatment was quantified using real-time reverse transcriptase-polymerase chain reaction (TaqMan.', 'Simvastatin did not influence the expression of duodenal ABCB1 and ABCC2. There was no significant pharmacokinetic interaction between simvastatin and talinolol. Duodenal ABCB1 mRNA content was significantly correlated with the AUC(0-infinity) (r = 0.627, P = 0.039) and C(max) (r = 0.718, P = 0.013) of oral talinolol. The ABCB1 and ABCC2 gene polymorphisms did not influence simvastatin and talinolol disposition. The half-life of the latter was significantly shorter in the nine carriers with a SLCO1B1*1b allele compared with the seven subjects with the wild-type SLCO1B1*1a/*1a genotype (12.2 +/- 1.6 h vs. 14.5 +/- 1.4 h, P = 0.01).",
            "output": [
                "Does simvastatin influence the intestinal P-glycoprotein and MPR2 , and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1 , ABCC2 and SLCO1B1 polymorphisms?"
            ]
        },
        {
            "id": "task847-51afb3f059a74576b05d4ce262a64613",
            "input": "To investigate and compare topoisomerase II-alpha expression in benign prostatic hyperplasia (BPH), prostate cancer of varying Gleason scores and hormone-insensitive prostate cancer.', 'The immunohistochemical expression of topoisomerase II-alpha antibody in the above-mentioned diagnostic categories was investigated and compared.', 'Increased expression of topoisomerase II-alpha was seen in the prostate cancers of Gleason scores 7 and 8-10 (p = 0.000) compared with prostate cancers of Gleason score 6 and BPH (p = 0.245). Statistically significant differences were found in the topoisomerase II-alpha gene expression between prostate cancers categorised by Gleason Score. Also, increased expression of topoisomerase II-alpha was seen in the known hormone-resistant prostate carcinomas compared with prostate cancers with no hormone treatment in the subgroup with Gleason scores 8-10, which approached statistical significance (p = 0.081). No statistically significant difference was observed in topoisomerase II-alpha expression between the groups with BPH and prostate carcinoma of Gleason score 6 (p = 0.245).",
            "output": [
                "Does topoisomerase II-alpha expression increase with increasing Gleason score and with hormone insensitivity in prostate carcinoma?"
            ]
        },
        {
            "id": "task847-693fde369eeb438e895c889153612c40",
            "input": "Multidrug resistance (MDR) has a potentially serious influence on cancer treatment and should be taken into consideration in the design and application of therapeutic regimens. It is mediated through the activity of cellular pumps.', 'To investigate whether furosemide, itself a pump-blocker, reverses MDR in an in vitro model.', 'An MDR bladder cancer cell line (MGH-u 1R) and its parental (drug sensitive) clone were exposed to epirubicin and furosemide, with the concentration of one drug fixed and that of the other serially diluted in a 96-well plate format. Both drugs formed the variable component in separate experiments. After a 1-h exposure, the cells were washed and replenished with fresh medium. To examine the toxicity of epirubicin and furosemide separately and in combination, monotetrazolium-based assays were carried out. Intracellular epirubicin distribution was assessed by confocal microscopy as a second index of resistance status after in vitro exposure.', 'MGH-u 1R cells incubated with furosemide showed distribution of drug similar to that in the parental cells (MGH-u 1 sensitive). Controls (without furosemide) continued to show a resistant pattern of fluorescence. In cytotoxicity assays furosemide appeared substantially non-toxic. Resistant cells in the toxicity titration experiments showed increased resistance to levels of furosemide over 500 mug/ml. Parental cells were made only marginally more sensitive against increased background toxicity.",
            "output": [
                "Does furosemide reverse multidrug resistance status in bladder cancer cells in vitro?"
            ]
        },
        {
            "id": "task847-69c29ff83cf145feaca4a83d0d9296cf",
            "input": "Limited data are available on intestinal MALT lymphoma owing to its relatively rare occurrence. The frequency of associated genetic changes was therefore analysed in intestinal MALT lymphoma to determine whether primary and secondary examples may be distinguished by their genetic profile.', 'Patients diagnosed with MALT lymphoma involving the intestine were evaluated and compared with 71 cases with localised gastric MALT lymphoma. Paraffin embedded samples were evaluated for t(11;18)(q21;q21) by reverse transcription polymerase chain reaction, and by fluorescence in situ hybridisation for t(14;18)(q32;q21), t(1;14)(p22;q32), and trisomies 3 and 18.', '30 consecutive patients with MALT lymphoma involving the intestine were identified: 16 had primary intestinal lymphoma and 14 had secondary MALT lymphoma. t(11;18)(q21;q21) was found in one third of the patients, but there was a significant difference between the secondary MALT lymphomas and the primary intestinal and gastric MALT lymphoma groups (57% v 12.5%, p = 0.019, and 57% v 24%, p = 0.022). Two patients with primary intestinal MALT lymphomas were positive for t(1;14)(p22;q32) and none was positive for t(14;18)(q32;q21). Primary intestinal MALT lymphoma had a significantly higher frequency of trisomies 3 or 18 (81% v 36%, p = 0.024; 81% v 14%, p<0.001), in contrast to secondary intestinal MALT lymphomas and localised gastric MALT lymphomas.",
            "output": [
                "Do mALT lymphoma associated genetic aberrations occur at different frequencies in primary and secondary intestinal MALT lymphomas?"
            ]
        },
        {
            "id": "task847-14076a699bb84d81bc067478c41ce18e",
            "input": "Using sonography, the bicornate and septate uterus as causes of failure of quinacrine sterilization (QS) are explored. Whether QS can be effectively performed on women with a bicornate or septate uterus is a question answered by a presentation of three such cases.', 'Three cases presented were part of a prospective nonrandomized study of QS in 205 women requesting sterilization at the Family Planning Clinic, School of Medicine of the Federal University of Minas Gerais, Belo Horizonte, Brazil. Sonography was performed on all patients before, during and after QS. Quinacrine was packaged as seven pellets in a modified Copper-T IUD inserter (Sipharm, Sisseln, Switzerland). Each woman received the first transcervical insertion of 252 mg of quinacrine during the follicular phase of the menstrual cycle, usually immediately after menses. One month later, a second insertion was similarly performed. Patients were advised to use an alternate method of birth control for 12 weeks to allow time for scarring of the oviducts. A blood pregnancy test was done before the QS procedure.', 'The diagnosis of a septate or bicornuate uterus was made by sonography in three of the 205 patients in the study. It was obvious that quinacrine had to be inserted into the two horns of such an anomalous uterus if the dissolved drug was to enter both fallopian tubes. Quinacrine dissolved into \"lakes of quinacrine,\" and sonographically could be seen at the top of the uterine fundus. For this clinical trial of 205 patients, there were 546 woman-years of follow-up, and the Pearl index was 0.73 per 100 woman-years (95% confidence limits: 0.02, 1.4).",
            "output": [
                "Does sonographic recognition of three cases of septate uteri diminish failures of quinacrine sterilization?"
            ]
        },
        {
            "id": "task847-d14fcfa5fe3f4273b758327fd88a087a",
            "input": "Leukemia inhibitory factor (LIF) is one of the key cytokines in the embryo implantation regulation. We investigated the prevalence of the LIF gene mutations in the population of infertile women that consisted of nulligravid and secondary infertile patients.', 'We designed a LIF gene mutation screening method that is based on the Temperature Gradient Gel Electrophoresis (TGGE). The population to screen consisted of 176 infertile women including group A of 147 nulligravid women and group B of 29 women with secondary infertility that had a history of either miscarriage or an ectopic pregnancy but no live births. The control population was comprised of 75 healthy fertile subjects. The groups of fertile controls and infertile patients were compared for statistically significant differences using the t-test.', 'Six potentially functional LIF gene mutations, the G to A transitions at the position 3400 leading to the valin to methionin exchange at codon 64 (V64M) in the AB loop region of the LIF protein, were detected. All of the six positive women were infertile. Four of them were nulligravid and two of them had history of spontaneous conception followed by early miscarriage. No positive TGGE samples were identified in the control group, which means that the frequency of functionally relevant mutations of the LIF gene in infertile women is significantly enhanced in comparison with controls (P<0.05, t-test).",
            "output": [
                "Are leukemia inhibitory factor gene mutations in the population of infertile women restricted to nulligravid patients?"
            ]
        },
        {
            "id": "task847-67aaab66cbb143dca95be294da63b51e",
            "input": "Traditionally cerebellar functions are thought to be related to control of tone, posture, gait, and coordination of skilled motor activity. However, there is an increasing body of evidence implicating the cerebellum in cognition, language, memory, and motor learning. Preterm infants are at increased risk of neurodevelopmental delay, cognitive dysfunction, and behavioral and emotional disturbances. The role of the cerebellum in these adverse outcomes is unclear.', 'The objective of this study was to determine whether absolute cerebellar volumes differ between term-equivalent preterm infants and term-born control infants and to assess whether cerebellar volume is influenced by any possible antenatal, perinatal, and postnatal factors.', 'The study compared the MR imaging cerebellar volume by using a manual quantification program of 113 preterm infants at term-equivalent age and 15 term-born control infants.', 'The median cerebellar volume of preterm at term-equivalent age was 25.4 cm3 and that of term-born control infants was 26.9 cm3. On initial analysis, there was a significant median difference of 2.0 cm3 (95% CI, 1.2 cm3 to 2.7 cm3) (2-sided P < .0001). However multiple regression analysis of perinatal variables showed that only infants with supratentorial lesions (P = .003) were significantly associated with the reduction in cerebellar volumes. The median cerebellar volumes were the following: supratentorial lesions, 18.9 cm3; no supratentorial lesions, 26.1 cm3; and term infants, 26.9 cm3 (analysis of variance, P < .0001). Hence, there was no significant difference in cerebellar volumes of preterm infants at term-equivalent age in the absence of supratentorial lesions. The median vermal volumes were 0.7 cm3 and were significantly related to cerebellar volumes both in preterm infants with and without lesions and in term-control infants.",
            "output": [
                "Are smaller cerebellar volumes in very preterm infants at term-equivalent age associated with the presence of supratentorial lesions?"
            ]
        },
        {
            "id": "task847-21b1a27616d747d2b38a0232017cd44f",
            "input": "Recent studies have identified MUC4 mucin as a ligand for activation of ErbB2, a receptor tyrosine kinase that modulates epithelial cell proliferation following epithelial damage in airways of asthmatics. In this study, we investigated the potential role of IL-4, one of the Th2 inflammatory cytokines persistent in asthmatic airways, in regulating MUC4 expression using a cell line NCI-H650.', 'Real time PCR analysis was performed to determine concentration and time dependent effects of IL-4 upon MUC4 expression. Nuclear run on experiments were carried out to explore potential transcriptional modulation. Western blotting experiments using a monoclonal antibody specific to ASGP-2 domain of MUC4 were performed to analyze MUC4 glycoprotein levels in plasma membrane fractions. To analyze potential signal transduction cascades, IL-4 treated confluent cultures were co-incubated, separately with a pan-JAK inhibitor, a JAK-3 selective inhibitor or a MEK-1, 2 (MAPK) inhibitor at various concentrations before MUC4 transcript analysis. Corresponding transcription factor activation was tested by western blotting using a monoclonal p-STAT-6 antibody.', 'MUC4 levels increased in a concentration and time specific fashion reaching peak expression at 2.5 ng/ml and 8 h. Nuclear run on experiments revealed transcriptional enhancement. Corresponding increases in MUC4 glycoprotein levels were observed in plasma membrane fractions. Pan-JAK inhibitor revealed marked reduction in IL-4 stimulated MUC4 levels and JAK3 selective inhibitor down-regulated MUC4 mRNA expression in a concentration-dependent fashion. In accordance with the above observations, STAT-6 activation was detected within 5 minutes of IL-4 stimulus. No effect in MUC4 levels was observed on using a MAPK inhibitor.",
            "output": [
                "Is iL-4 induced MUC4 enhancement in respiratory epithelial cells in vitro mediated through JAK-3 selective signaling?"
            ]
        },
        {
            "id": "task847-8ed3bf9d6d85460ab46ca572fbaad134",
            "input": "Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile.', 'Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC.', 'Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples.",
            "output": [
                "Does 3-phosphoinositide-dependent protein kinase-1 ( PDK1 ) promote invasion and activation of matrix metalloproteinases?"
            ]
        },
        {
            "id": "task847-3b98d5ade93144d2bf61f9bb30ad642f",
            "input": "The issue of platelet function in infants and neonates is of interest, and current data are debatable. A new method for assessing platelet function involves using the cone and plate(let) analyzer (CPA), applicable for small (0.2 ml) whole blood volumes. We used polystyrene surface-coated plates to evaluate cord blood neonatal platelet function under flow. One hundred and sixty full-term and 29 preterm infants born at the Sheba Medical Center between March 2003 and January 2004 were evaluated for platelet adhesion measured as surface coverage (SC; the percentage of total area covered by platelets) and platelet aggregation, defined as the average size (AS) of the aggregates. Platelets from preterm infants displayed less platelet adhesion than did those from full-term infants. Platelet SC correlated with gestational age in all infants (p < 0.05), and both groups exhibited similar aggregation (AS). AS values, however, were significantly lower than the normal adult range in our laboratory. Infants born to mothers with pregnancy-induced hypertension displayed significantly lower SC. No association was found between CPA and postnatal complications.",
            "output": [
                "Does platelet function of newborns as tested by cone and plate ( let ) analyzer correlate with gestational Age?"
            ]
        },
        {
            "id": "task847-2e355716c26046f09e42c3177f1eed74",
            "input": "To demonstrate that in APPswe/PS1DeltaE9 transgenic mice, gene gun mediated Abeta42 gene vaccination elicits a high titer of anti-Abeta42 antibodies causal of a significant reduction of Abeta42 deposition in brain.', 'Gene gun immunization is conducted with transgenic mice using the Abeta42 gene in a bacterial plasmid with the pSP72-E3L-Abeta42 construct. Enzyme-linked immunoabsorbent assays (ELISA) and Western blots are used to monitor anti-Abeta42 antibody levels in serum and Abeta42 levels in brain tissues. Enzyme-linked immunospot (ELISPOT) assays are used for detection of peripheral blood T cells to release gamma-interferon. Immunofluorescence detection of Abeta42 plaques and quantification of amyloid burden of brain tissue were measured and sections were analyzed with Image J (NIH) software.', 'Gene gun vaccination with the Abeta42 gene resulted in high titers of anti-Abeta42 antibody production of the Th2-type. Levels of Abeta42 in treated transgenic mouse brain were reduced by 60-77.5%. The Mann-Whitney U-test P=0.0286.",
            "output": [
                "Does abeta42 gene vaccination reduce brain amyloid plaque burden in transgenic mice?"
            ]
        },
        {
            "id": "task847-f3fd3cd0515b4264b26b179451a21b7a",
            "input": "Cardiotrophin-1 (CT-1) is a cytokine involved in the growth and survival of cardiac cells via activation of the Janus activated kinase/signal transducer activator of transcription (JAK/STAT). Statins, 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have effects that extend beyond cholesterol reduction and inhibit vascular smooth muscle cell (VSMC) proliferation and cardiac hypertrophy. However, whether stains also can inhibitin vitromyocardial hypertrophy or not still remains elusive. The purpose of this study was to explore the effects of simvastatin on the hypertrophy of cultured rat cardiomyocytes induced by CT-1 and to investigate whether this effect was mediated via JAK-STAT signaling pathway.', 'Primary cardiomyocytes from 2-day-old (P2) rats were cultured, stimulated with CT-1, and treated with various concentration of simvastatin. Incorporation of [(3)H] leucine, reverse transcription-polymerase chain reaction and western blotting techniques were used to investigate cardiacmyocyte size, ANP mRNA and JAK-STAT protein expression. Simvastatin was proved, in a dose-independent manner, to decrease cardiacmyocytes size as well as protein synthesis, and inhibit ANP mRNA synthesis and JAK-STAT protein expression induced by CT-1 in cardiacmyocytes.",
            "output": [
                "Does simvastatin attenuate hypertrophic responses induced by cardiotrophin-1 via JAK-STAT pathway in cultured cardiomyocytes?"
            ]
        },
        {
            "id": "task847-00be2a623d6b485ab87ba695dd2e9e20",
            "input": "Ephrin ligands and Eph receptors play important roles for cell behavior and movement by transducing bidirectional signaling into interacting cells. Since we found that the expression of ephrinB2 in the hematopoietic progenitor cell line was changed by coculture with stromal cells, we tried to examine the function of ephrinB2 in the hematopoietic microenvironment.', \"Expression of ephrinB2 was measured by flow cytometry and reverse transcriptase polymerase chain reaction in the bone marrow (BM) hematopoietic cells and the stroma-dependent hematopoietic cell line (DFC-28) cocultured with stromal cells. Effect of ephrinB2 on the cells' behavior was monitored by overexpression of ephrinB2 cDNA in mouse pre-B-cell line (70z/3).\", 'EphrinB2 expression in DFC-28 cells was modulated by two different stromal cells; ephrinB2 expression was high in DFC-28 cells when cocultured with MSS62 cells, whereas it was low when they were cocultured with TBR31-1 cells. Expression of EphB4, a receptor for ephrinB2, was detected in MSS62 cells but not in TBR31-1 cells. Similarly, BM hematopoietic cells did not express ephrinB2, but most of the BM cells expressed ephrinB2 after coculture with stromal cells. Ectopic expression of ephrinB2 in 70z/3 cells acquires specific binding to EphB4 and leads to significant decline in the locomotive activity underneath stromal cells.",
            "output": [
                "Do stromal cells modulate ephrinB2 expression and transmigration of hematopoietic cells?"
            ]
        },
        {
            "id": "task847-f32273cace2c4014810a62493f648078",
            "input": "Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate.', 'By comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the alpha3 domain, but our results suggest that homogenisation also concerns certain residues of the alpha1-alpha2 codomain that lie outside the antigen recognition site.",
            "output": [
                "Is the orthology of HLA-E and H2-Qa1 hidden by their concerted evolution with other MHC class I molecules?"
            ]
        },
        {
            "id": "task847-30def6b813464749b236b9769f73089f",
            "input": "The conventional view that admission lactate levels predict outcome in trauma patients stems from simple comparisons of mean blood levels between groups and small sample sizes. To better address this question, we performed more rigorous statistical analyses of lactate in a larger patient sample.', 'We prospectively collected data on admission lactate and outcomes in 5,995 patients admitted to an urban, university-based trauma center. The ability of admission lactate to predict mortality was assessed by logistic regression, calculation of positive predictive values (PPV), and measurement of areas under receiver operating characteristic (ROC) curves.', 'Differences between survivors and nonsurvivors in means of most proposed prognosticators was again demonstrated. However, the large overlap in these variables between survivors and nonsurvivors prevented clinically useful predictions. The overall PPV of elevated lactate was only 5.4%. Even in severely injured patients (Injury Severity Score >20; mortality 23%), elevated admission lactate level was a poor predictor of outcome. ROC analyses found no useful sensitivity threshold overall or after stratification by age, sex, Glasgow Coma Scale score, revised trauma score, or mechanism of injury.",
            "output": [
                "Do admission serum lactate levels predict mortality in the acutely injured patient?"
            ]
        },
        {
            "id": "task847-451a3da278af4356bb2a62c4880a0124",
            "input": "Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. Three isoforms of HO have been discovered. Recently, HO-1 has been found to be upregulated after allergic inflammations of the lower airway.', 'The objective of this study was to address the expression of HO isoenzymes 1 and 2 in the nasal mucosa of patients with allergic rhinitis as well as normal control subjects.', 'Nasal mucosa from 30 patients with persistent allergic rhinitis as well as from 10 normal volunteers was used in this study. We used immunofluorescent technique, Western blotting, and real-time quantitative polymerase chain reaction to localize and quantify the expression of these isoenzymes in normal and allergic human nasal tissues.', 'We found that HO-1 is expressed in the epithelial cells of seromucinous glands and macrophages with significant upregulation of its glandular expression in allergic rhinitis but with no difference in its macrophage expression between the study groups in contrast to HO-2 that is expressed in the vascular endothelial lining cells as well as macrophages with no marked difference between the study groups.",
            "output": [
                "Is heme oxygenase ( HO ) -1 upregulated in the nasal mucosa with allergic rhinitis?"
            ]
        },
        {
            "id": "task847-04edeb326b444dd4b31dc60111e93062",
            "input": "One of the major contributors to brain injury after subarachnoid hemorrhage (SAH) is oxidative stress, and 1 of the major enzymatic sources of superoxide anion production in the brain is NADPH oxidase. Therefore, we studied whether hyperbaric oxygen (HBO) suppresses neuronal NADPH oxidase in a rat model of SAH.', 'Eighty-three Sprague-Dawley male rats were assigned to sham, SAH, and SAH treated with HBO groups. SAH was induced by endovascular perforation. HBO (2.8 atmospheres absolutes for 2 hours) was started at 1 hour after perforation. Rats were euthanized at 6 or 24 hours, and brains were collected for histology, biochemistry, and molecular biology studies including NADPH oxidase activity, gp91phox mRNA expression, and lipid peroxidation assays. Mortality and neurological scores were evaluated.', 'We observed an increased neuronal immunoreactivity of gp91phox at 24 hours after SAH. The upregulation of gp91phox mRNA was associated with increased oxidative stress. HBO decreased NADPH oxidase expression, activity, and the level of oxidative stress at 24 hours after SAH. HBO reduced neuronal injury and improved functional performance throughout the observation period.",
            "output": [
                "Does hyperbaric oxygen suppress NADPH oxidase in a rat subarachnoid hemorrhage model?"
            ]
        },
        {
            "id": "task847-65b6d378f028439e9e8e77a917a48ddd",
            "input": "Apart from anecdotal reports implicating Helicobacter pylori (HP) in the development of extragastric mucosa associated lymphoid tissue (MALT) lymphoma, no large scale prospective studies have been performed on this topic.', 'A total of 77 patients with extragastric MALT lymphoma were prospectively studied. The presence or absence of HP was tested by histology, urease breath test, and serology. Patients were also tested for hepatitis A, B, and C and autoimmune conditions along with assessment of MALT lymphoma-specific genetic changes.', 'Evidence for infection with HP was present in 35 of 77 patients (45%), and three of 75 patients tested (4%) were positive for hepatitis C and one for hepatitis B. All patients with HP-infection underwent eradication, 16 before initiation of further therapy. Apart from one patient with lymphoma involving parotid and colon, who achieved regression of the colonic lesions, none of these 16 patients showed regression of the lymphoma after a median follow-up of 14 months (range, 8 to 48+ months) before initiation of definitive treatment. No correlation between HP-status, localization, stage, autoimmune diseases, and genetic findings was seen.",
            "output": [
                "Is antibiotic treatment effective in patients infected with Helicobacter pylori suffering from extragastric MALT lymphoma?"
            ]
        },
        {
            "id": "task847-d4f96a648d3f49529621e77c572c1a92",
            "input": "In general the bacterial count in freshly donated blood is low and even lower in the corresponding platelet concentrates (PCs). By use of flow cytometry (FACS) for sterility testing, the reliability of early versus later sampling times was evaluated.', 'Blood donations were spiked with various numbers of Staphylococcus epidermidis, Staphylococcus aureus, Bacillus cereus, and Klebsiella pneumoniae. The corresponding PCs were prepared by the buffy-coat method and stored at 22 degrees C. A 20-mL sample was collected from each PC directly after preparation and after 8 hours. Samples were stored at 35 degrees C. Sterility testing of both PCs and samples was by FACS analysis at different time points.', 'All stored PCs were found positive by FACS analysis, with detection times ranging between 8 and 24 hours (K. pneumoniae, B. cereus), 8 and 91 hours (S. aureus), and 144 hours (S. epidermidis). In the samples incubated at 35 degrees C, bacteria were detected after 8 to 19 hours (K. pneumoniae, B. cereus), 8 to 67 hours (S. aureus), and 19 to 43 hours (S. epidermidis). Some of the samples did not contain bacteria.",
            "output": [
                "Does sterility testing of platelet concentrate prepared from deliberately infected blood donations?"
            ]
        },
        {
            "id": "task847-75e37919f45c436aa2e02b9d2447d513",
            "input": "Hypoxia is associated with human non-small cell lung cancers (NSCLC), which are highly resistant to chemotherapy. The hypoxia inducible factor (HIF) as a transcription factor in response to hypoxia indicates that it could be a novel, tumor-specific target for anticancer therapy. We hypothesized that disruption of HIF pathway through lentiviral vector-mediated HIF-1alpha RNA interference (RNAi) could reverse the hypoxia-induced resistance to chemotherapy.', 'We transfected Human NSCLC cell lines, SPCA1 and A549 with HIF-1alpha specific RNAi lentiviral vectors as well as controls. HIF-1alpha silenced cells [SPCA1/HIF-1alpha(-) and A549/HIF-1alpha(-)] were screened by blasticidin. They were incubated in 19 or 0.5% O2 for 16 h followed by the assessment of chemosensitivity to cisplatin and doxorubicin with MTT and clonogenic assays. Quantitative RT-PCR and Western blot analysis were used to detect the expressions of HIF-1alpha mRNA and protein, respectively. Moreover, flow cytometry was used to monitor the expression of P-glycoprotein.', 'Exposure of SPCA1 and A549 cells to 0.5% O2 significantly increased resistance to cisplatin and doxorubicin, in contrast to cells incubated in normoxia. Transduction of SPCA1 with HIF-1alpha RNAi vector resulted in sequence specific silencing with 87.2 and 84.6% decreases of HIF-1alpha mRNA transcription and 97.3 and 94.8% of protein expressions in normoxia and hypoxia, respectively. Correspondingly, they are 89.2, 89.9% and 97.2, 88.4% decreases in A549 cells. Hypoxia-induced resistance to cisplatin and doxorubicin were reversed in SPCA1/HIF-1alpha(-) and A549/HIF-1alpha(-) cells. There was no significant P-glycoprotein increase induced by hypoxia in NSCLC cells.",
            "output": [
                "Is hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer inhibited by silencing of HIF-1alpha gene?"
            ]
        },
        {
            "id": "task847-5a9c2b7e6ed241eaa677dc0443b55f87",
            "input": "In experimental peritoneal dialysis (PD) studies, the occurrence of peritonitis is a confounder in the interpretation of effects of chronic peritoneal exposure to dialysis solutions. Since fluid cannot be drained in most experimental PD models in the rat, it is impossible to diagnose peritonitis based on dialysate white blood cell counts. To study the value of serum markers for the presence of peritonitis, alpha-2-macroglobulin (alpha2M) and albumin were measured in rats with and without peritonitis after chronic exposure to dialysis solutions. To further investigate the time course of these markers in relation to the severity of peritonitis, nondialyzed rats were challenged with increasing numbers of bacteria and followed for 28 days.', 'In the first study, alpha2M and albumin were measured in rats exposed to glucose/lactate-based dialysis fluid before sacrifice. A comparison was made between animals with peritonitis, as judged from the presence of extensive infiltrates after sacrifice (gold standard) and/or clinical signs of peritonitis, or absence of peritonitis and infiltrates. In the second study, rats were intraperitoneally (IP) injected with 3 different concentrations of Staphylococcus aureus, and serum alpha2M and albumin were measured at various time points.', 'In the first study, serum alpha2M was higher and serum albumin was lower in animals with peritonitis compared to animals without peritonitis (both p < 0.05). In the second study, induction of alpha2M was clearly dependent on the inoculum concentration. Peak values of alpha2M were found at days 1 and 3. At all time points after inoculation, alpha2M was higher in all injected groups compared to the control group. Serum albumin values decreased in the highest inoculum group and remained decreased until 28 days after IP injection. Despite a low sensitivity, serum alpha2M > 40 mg/L and albumin < 32 g/L had a specificity of 100% for peritonitis.",
            "output": [
                "Are alpha-2-macroglobulin and albumin useful serum proteins to detect subclinical peritonitis in the rat?"
            ]
        },
        {
            "id": "task847-5be2013341dc4961889601e3b75fc35f",
            "input": "Growth factor therapy provides a therapeutic alternative for \"no option\" patients with coronary disease. Fibroblast Growth Factor-2 (FGF-2) predominantly stimulates angiogenesis, the growth of new capillaries, whereas Monocyte Chemoattractant Protein-1 (MCP-1) is considered an arteriogenic agent. We hypothesised a synergetic effect of FGF-2 and MCP-1 in ischemic myocardium.', 'A severe coronary stenosis was created in pigs. After one week, chronic ischemia was confirmed by angiography, echocardiography, reduced ejection fraction, and increase of marker enzymes. FGF-2, MCP-1, both, or vector only were then injected intramyocardially as plasmid DNA in the impaired area. Regional contractility and number of capillaries and arterial vessels were evaluated after three months.', 'FGF-2, FGF-2+MCP-1, and vector, but not MCP-1 alone improved regional contractility at rest, whereas only FGF-2 alone ameliorated function under stress conditions. Angiogenesis in the ischemic area was stimulated by FGF-2 compared to MCP-1. In contrast, MCP-1 induced arteriogenesis relative to FGF-2.",
            "output": [
                "Does improvement of contractility accompany angiogenesis rather than arteriogenesis in chronic myocardial ischemia?"
            ]
        },
        {
            "id": "task847-95451bc1ec2a4e8e891291c9150a478f",
            "input": "The purpose of this study was to evaluate the impact of FDG-PET following chemoradiotherapy (CRT) on treatment planning and survival in patients with oesophageal cancer (OC).', 'Fifty-three consecutive OC patients had a post-treatment PET scan to evaluate tumour response to CRT prior to possible surgery. Baseline pre-CRT PET was performed in 33 patients. Prospectively recorded post-CRT management plans were compared with post-PET treatment. High impact was defined as a change in treatment intent or modality. Survival was analysed using the Kaplan-Meier product limit method and Cox proportional hazards regression model.', 'After completion of CRT, 23/53 patients (43%) achieved complete metabolic response (CMR), as compared with only four (8%) with complete response on computed tomography. High PET impact was observed in 19 patients (36%). CMR was strongly predictive of survival (p<0.008) on multivariate analysis. CMR patients in whom resection was not performed had comparable survival to those (CMR and non-CMR) who underwent resection.",
            "output": [
                "Does fDG-PET status following chemoradiotherapy provide high management impact and powerful prognostic stratification in oesophageal cancer?"
            ]
        },
        {
            "id": "task847-32a6cc0070b1421a9129bd807c17b597",
            "input": "The goal of this study was to compare language lateralization between pediatric epilepsy patients and healthy children.', 'Two groups of subjects were evaluated with functional magnetic resonance imaging (fMRI) by using a silent verb-generation task. The first group included 18 pediatric epilepsy patients, whereas the control group consisted of 18 age/gender/handedness-matched healthy subjects.', 'A significant difference in hemispheric lateralization index (LI) was found between children with epilepsy (mean LI =-0.038) and the age/gender/handedness-matched healthy control subjects (mean LI=0.257; t=6.490, p<0.0001). A dramatic difference also was observed in the percentage of children with epilepsy (77.78%) who had atypical LI (right-hemispheric or bilateral, LI<0.1) when compared with the age/gender/handedness-matched group (11.11%; chi(2)=16.02, p<0.001). A linear regression analysis showed a trend toward increasing language lateralization with age in healthy controls (R(2)=0.152; p=0.108). This association was not observed in pediatric epilepsy subjects (R(2)=0.004, p=0.80). A significant association between language LI and epilepsy duration also was found (R(2)=0.234, p<0.05).",
            "output": [
                "Does fMRI show atypical language lateralization in pediatric epilepsy patients?"
            ]
        },
        {
            "id": "task847-85c786d0912d46c79687c4c91e706d48",
            "input": "Peroxisome proliferator activated receptor gamma (PPARgamma) is expressed in epithelial cells, macrophage, and T and B lymphocytes. Ligand induced activation of PPARgamma was reported to attenuate colitis activity but it is not clear whether this protection is mediated by epithelial or leucocyte PPARgamma.', 'Mice with targeted disruption of the PPARgamma gene in intestinal epithelial cells, generated using a villin-Cre transgene and floxed PPARgamma allele and designated PPARgamma(DeltaIEpC), were compared with littermate mice having only the PPARgamma floxed allele with no Cre transgene that expressed PPARgamma in the gut, designated PPARgamma(F/F). Colitis was induced by administering dextran sodium sulphate (DSS) and the two mouse lines compared for typical symptoms of disease and expression of inflammatory cytokines.', 'PPARgamma(DeltaIEpC) mice displayed reduced expression of the PPARgamma target genes ADRP and FABP in the gut but were otherwise normal. Increased susceptibility to DSS induced colitis, as defined by body weight loss, colon length, diarrhoea, bleeding score, and altered histology, was found in PPARgamma(DeltaIEpC) mice in comparison with PPARgamma(F/F) mice. Interleukin (IL)-6, IL-1beta, and tumour necrosis factor alpha mRNA levels in colons of PPARgamma(DeltaIEpC) mice treated with DSS were higher than in similarly treated PPARgamma(F/F) mice. The PPARgamma ligand rosiglitazone decreased the severity of DSS induced colitis and suppressed cytokine production in both PPARgamma(F/F) and PPARgamma(DeltaIEpC) mice.",
            "output": [
                "Does peroxisome proliferator activated receptor gamma in colonic epithelial cells protect against experimental inflammatory bowel disease?"
            ]
        },
        {
            "id": "task847-f2846a405562484ab98bc5a9d62a9258",
            "input": "Group I metabotropic glutamate receptors (mGluRs) have been reported to regulate N-methyl-d-aspartate (NMDA) receptor function in various brain regions. The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate NMDA antagonists such as PCP and MK-801-induced behavioural responses. In the present study, the role of group I mGluRs on ketamine- and propofol-induced general anaesthesia was examined.', 'Mice were pretreated with various doses of the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG), selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) and mGluR5 antagonist MPEP followed by administration of ketamine (120 mg kg(-1)) or propofol (140 mg kg(-1)) to induce anaesthesia. The duration of loss of righting reflex was recorded.', 'DHPG and CHPG antagonized and MPEP potentiated ketamine-induced anaesthesia in a dose-dependent manner. CPCCOEt was ineffective. However, propofol-induced anaesthesia was not affected after manipulating mGluR1 and mGluR5 receptors.",
            "output": [
                "Is ketamine , but not propofol , anaesthesia regulated by metabotropic glutamate 5 receptors?"
            ]
        },
        {
            "id": "task847-89ae55db4db14a01a52b70cbd13e6c02",
            "input": "Resistance to cisplatin-centered chemotherapy is a major cause of treatment failure in human ovarian cancer. Whereas PTEN, a tumor suppressor gene product, is believed to promote apoptosis primarily via inactivation of the PI3K/Akt cell survival pathway, recent evidence suggests that PTEN may function independently of this pathway. Activation of p53 is a key determinant of sensitivity to cisplatin-induced apoptosis. Whether PTEN can facilitate cisplatin sensitivity, and this involves the activation of p53, remains unclear. In this study, we determined whether and how PTEN over-expression sensitizes ovarian cancer cells to CDDP-induced apoptosis.', 'Using pairs of chemosensitive and chemoresistant ovarian cancer cell lines (OV20028 vs. C13* and A2780-s vs. A2780-cp) as an in vitro model, we have examined the influence of PTEN over-expression in regulation of cisplatin-induced apoptosis. Apoptosis was assessed morphologically by Hoechst staining and confirmed by the detection of cleaved products of caspase-3 and PARP by Western blot. Over-expression of PTEN by PTEN cDNA transfection up-regulates p53 content and increases the sensitivity of chemoresistant cells to cisplatin-induced apoptosis without detectable changes in the levels of phosphorylated Akt and FKHR as well as FasL mRNA abundance as determined by Western blot and RT-PCR, respectively. PTEN-mediated chemosensitization was attenuated by p53 down-regulation by siRNA in C13*, a chemoresistant wild-type p53 cell. Moreover, PTEN over-expression failed to sensitize the chemoresistant p53 mutant ovarian cancer cell line A2780-cp to cisplatin-induced apoptosis, unless wild-type p53 was reconstituted by adenoviral p53 infection.",
            "output": [
                "Does over-expression of PTEN sensitize human ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner?"
            ]
        },
        {
            "id": "task847-17f851f545c345b2b0e720b42dd708c5",
            "input": "To describe and critically appraise available methods for handling missing variance data in meta-analysis (MA).', 'Systematic review. MEDLINE, EMBASE, Web of Science, MathSciNet, Current Index to Statistics, BMJ SearchAll, The Cochrane Library and Cochrance Colloquium proceedings, MA texts and references were searched. Any form of text was included: MA, method chapter, or otherwise. Descriptions of how to implement each method, the theoretic basis and/or ad hoc motivation(s), and the input and output variable(s) were extracted and assessed. Methods may be: true imputations, methods that obviate the need for a standard deviation (SD), or methods that recalculate the SD.', 'Eight classes of methods were identified: algebraic recalculations, approximate algebraic recalculations, imputed study-level SDs, imputed study-level SDs from nonparametric summaries, imputed study-level correlations (e.g., for change-from-baseline SD), imputed MA-level effect sizes, MA-level tests, and no-impute methods.",
            "output": [
                "Does a systematic review identify a lack of standardization in methods for handling missing variance data?"
            ]
        },
        {
            "id": "task847-71c61a219efc430ebbb453ff5f6f1979",
            "input": "To develop a specific SARS virus-targeted antibody preparation for emergent prophylaxis and treatment of SARS virus infection.', 'By using phage display technology, we constructed a naive antibody library from convalescent SARS patient lymphocytes. To obtain the neutralizing antibody to SARS virus surface proteins, the library panning procedure was performed on purified SARS virions and the specific Fab antibody clones were enriched by four rounds of repeated panning procedure and screened by highthroughput selection. The selected Fab antibodies expressed in the periplasma of E. coli were soluble and further purified and tested for their binding properties and antiviral function to SARS virus. The functional Fab antibodies were converted to full human IgG antibodies with recombinant baculovirus/insect cell systems and their neutralizing activities were further determined.', 'After four rounds of the panning, a number of SARS-CoV virus-targeted human recombinant Fab antibodies were isolated from the SARS patient antibody library. Most of these were identified to recognize both natural and recombinant SARS spike (S) proteins, two Fab antibodies were specific for the virus membrane (M) protein, only one bound to SARS-CoV nucleocapsid protein. The SARS-CoV S and M protein-targeted Fab or IgG antibodies showed significant neutralizing activities in cytopathic effect (CPE) inhibition neutralization test, these antibodies were able to completely neutralize the SARS virus and protect the Vero cells from CPE after virus infection. However, the N protein-targeted Fab or IgG antibodies failed to neutralize the virus. In addition, the SARS N protein-targeted human Fab antibody reacted with the denatured N proteins, whereas none of the S and M protein specific neutralizing antibodies did. These results suggested that the S and M protein-specific neutralizing antibodies could recognize conformational epitopes which might be involved in the binding of virions to cellular receptors and the fusion activity of the virus.",
            "output": [
                "Do sARS patients-derived human recombinant antibodies to S and M proteins efficiently neutralize SARS-coronavirus infectivity?"
            ]
        },
        {
            "id": "task847-27ec8492ed254cafb6b68d120d87e13b",
            "input": "Despite advances in neurosurgical management, aneurismal subarachnoid hemorrhage (aSAH) still has high mortality and morbidity. This study aimed to clarify how delaying hospital admission after aSAH contributes to worse prognosis even today and to find the possibility for an improvement of its prognosis by early admission.', 'Four hundred twenty-one consecutive patients are the basis for this study. Cause of delay was classified into 5 categories: patient delay (PD), doctor delay (DD), transportation delay (TD), no delay (ND) (within 2 hours of onset), and others. Condition of each patient was assessed at time of onset and admission using H&K. The relationships between cause of delay and worsening of Hunt and Kosnik grading (H&K) were examined.', 'The median delay time was 1.7 days. Only 41% of patients visited our institution without delay. Admission delay, especially PD and DD, exhibited a significant correlation to worsening of H&K. In addition to nondirect admission, misdiagnosis or delayed diagnosis contributed significantly to worsening of H&K. Incidence of DD has declined in recent years, whereas that of PD has increased. Consequently, no change in total number of delays was found.",
            "output": [
                "Does the key to improving prognosis for aneurysmal subarachnoid hemorrhage remain in the pre-hospitalization period?"
            ]
        },
        {
            "id": "task847-63a854b553214a8f971a8aa770cb5f14",
            "input": "Recently described slow-cooling cryopreservation protocols involving elevated sucrose concentration have improved survival frequencies of human oocytes, potentially overcoming a major hurdle that has limited the adoption of oocyte storage. Because implantation rates of embryos from frozen oocytes remain generally low, it is still debated whether, irrespective of survival rates, this form of cryopreservation leads inevitably to the disruption or complete loss of the metaphase II (MII) spindle.', 'Human oocytes with an extruded polar body I (PBI) were cryopreserved using a slow-cooling method including 1.5 mol/l propane-1,2-diol (PrOH) and alternative sucrose concentrations (either 0.1 or 0.3 mol/l) in the freezing solution. Fresh control and frozen-thawed survived oocytes were analysed by confocal microscopy to evaluate MII spindle and chromosome organizations.', 'Of the 104 oocytes included in the unfrozen group, 76 (73.1%) displayed normal bipolar spindles with equatorially aligned chromosomes. Spindle and chromatin organizations were significantly affected (50.8%) after cryopreservation involving lower sucrose concentration (61 oocytes), whereas these parameters were unchanged (69.7%) using the 0.3 mol/l sucrose protocol (152 oocytes).",
            "output": [
                "Does sucrose concentration influence the rate of human oocytes with normal spindle and chromosome configurations after slow-cooling cryopreservation?"
            ]
        },
        {
            "id": "task847-bb2e74755aa9440699ee06823808328e",
            "input": "A gastric tube is commonly used in thoracic esophageal reconstruction. When a gastric tube is not available, pedicled jejunum transfer and colonic interposition are alternative methods. Oral end of the reconstructed esophagus occasionally has poor blood flow and may result in partial necrosis of the oral segment. We performed additional microvascular blood flow augmentation, the \"supercharge\" technique, to improve a blood flow circulation in the oral segment of the reconstructed esophagus.', 'A series of 86 esophageal reconstructions with microvascular blood flow augmentation using the \"supercharge\" technique were performed. Reconstructive methods included a gastric tube in five patients, a gastric tube combined with a free jejunual graft in one, an elongated gastric tube in eight, a pedicled colonic interposition in 22, and a pedicled jejunum in 50. Recipient vessels were used in neck or chest region.', 'The color and blood flow of the transferred intestine appeared greatly improved after microvascular blood flow augmentation. Thrombosis was noticed in three patients during the surgery, and all thrombosies were salvaged by re-anastomosis. There were only three patients with partial graft necrosis of oral segment, two patients with anastomotic leakage, one anastomotic stricture.",
            "output": [
                "Do variation of microvascular blood flow augmentation -- supercharge in esophageal and pharyngeal reconstruction?"
            ]
        },
        {
            "id": "task847-97f060cd7d084c96b72182036f66eed7",
            "input": "Current staging for renal cancer (RC) does not directly rely on tumor size. We examined the increment in accuracy related to inclusion of pathologically determined tumor size in prediction of nodal metastases (N+), distant metastases (M+), and cancer-specific survival (CSS).', 'Partial or radical nephrectomy was performed in 2245 patients with clear cell histology. Pathologic stages were T1a in 566, T1b in 490, T2 in 303, T3 in 831, and T4 in 55 patients. Tumor size was 0.5-25 cm (mean, 6.8). Multivariate models relied on 1997 and 2002 TNM variables and addressed N+, M+ disease, and CCS. Their accuracy was compared according to either the presence or absence of tumor size.', 'In all univariate and multivariate models, tumor size was a statistically significant predictor of all outcomes (p< or =0.001). In all multivariate models, tumor size added between 3.7% and 0.8% to predictive accuracy of either 1997 or 2002 TNM categories.",
            "output": [
                "Does tumor size improve the accuracy of TNM predictions in patients with renal cancer?"
            ]
        },
        {
            "id": "task847-8417a70ad39647a987b0d84e119b9087",
            "input": "Bipolar disorder is associated with deficits in cognitive functioning. The etiology of cognitive impairment in bipolar disorder may relate to both genetic and environmental factors. A valine/methionine polymorphism of the catechol O-methyltransferase gene at amino acid 158 (COMT Val158Met polymorphism) has been identified as a risk factor for cognitive impairment in schizophrenia. Serological evidence of infection with herpes simplex virus type 1 (HSV-1) has also been identified as a risk factor for cognitive impairment in bipolar disorder.', 'We used Taqman technology to measure COMT Val158Met alleles in 107 individuals with bipolar disorder and in 95 controls. We also measured antibodies to HSV-1 in sera obtained from the same individuals. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status and the Letter-Number Sequencing Test. The effects of the COMT Val158Met polymorphism and antibodies to HSV-1 on cognitive functioning were analyzed with multinomial logistic regressions.', 'The COMT Val158Val genotype and serological evidence of infection with HSV-1 are independent risk factors for cognitive impairment in individuals with bipolar disorder, particularly in the domains of immediate and delayed memory. Individuals with bipolar disorder with the COMT158 Val/Val genotype and serological evidence of HSV-1 infection were more than 85 times more likely to be in the lowest quintile of cognitive functioning when compared with the highest quintile when controlling for potential confounding variables such as symptom severity and education. Control individuals did not display this association.",
            "output": [
                "Are the catechol O-methyltransferase Val158Met polymorphism and herpes simplex virus type 1 infection risk factors for cognitive impairment in bipolar disorder : additive gene-environmental effects in a complex human psychiatric disorder?"
            ]
        },
        {
            "id": "task847-5af1e3be3ae04720acd8f08c6c8dbbc6",
            "input": "Patients with respiratory failure due to progressive muscle weakness often require chronic ventilatory support, but many do not make decisions regarding ventilation prior to a crisis. We studied the use of non-invasive ventilation as a tool to enable communication and facilitate decision-making regarding chronic ventilation.', 'Patients with profound muscle weakness and acute respiratory failure, were supported or weaned by non-invasive positive or negative pressure ventilation. The patients were then interviewed and their informed autonomous decisions were used to plan their future management.', 'Non-invasive ventilation could be used safely to support patients with acute respiratory failure until decisions regarding chronic ventilation are made and as an alternative means of ventilation for those who refuse tracheostomy.",
            "output": [
                "Does non-invasive Mechanical Ventilation enhance Patient Autonomy in Decision-Making Regarding Chronic Ventilation?"
            ]
        },
        {
            "id": "task847-af0ce3e73ab340aab39cf2e7571310d0",
            "input": "Subthalamic nucleus deep brain stimulation (STN0 DBS) is a widely performed surgical treatment in PD. However, the relationship between motor results and cognitive/behavioural modifications is unclear.', 'This study investigated the correlation patterns of the motor, cognitive and behavioural consequences of STN DBS with respect to positioning of the active contact.', 'Fifty-eight consecutive PD patients having undergone STN DBS were assessed pre-operatively and 12 months after surgery.', 'Motor, cognitive and behavioural results were neither correlated to each other nor linked to the position of the active contact. Three patients with a history of pre-operative, dopaminergic psychosis or post-surgical confusion became demented. Age and a distant history of depression were associated with the occurrence of post-surgical depression.",
            "output": [
                "Are stimulation of the subthalamic nucleus in Parkinson 's disease : cognitive and affective changes linked to the motor outcome?"
            ]
        },
        {
            "id": "task847-681ec9f527bc4df9a3464e36deb290df",
            "input": "It has been suggested that drug-paired stimuli (S+) control addictive behaviour by eliciting an explicit mental representation or expectation of drug availability.', 'The aim of the present study was to test this hypothesis by determining whether the behavioural control exerted by a tobacco-paired S+ in human smokers would depend upon the S+ eliciting an explicit expectation of tobacco.', 'In each trial, human smokers (n=16) were presented with stimuli for which attention was measured with an eyetracker. Participants then reported their cigarette reward expectancy before performing, or not, an instrumental tobacco-seeking response that was rewarded with cigarette gains if the S+ had been presented or punished with cigarette losses if the S- had been presented. Following training, participants rated the pleasantness of stimuli.', 'The S+ only brought about conditioned behaviour in an aware group (those who expected the cigarette reward outcome when presented with the S+). This aware group allocated attention to the S+, performed the instrumental tobacco-seeking response selectively in the presence of the S+ and rated the S+ as pleasant. No conditioned behaviour was seen in the unaware group (those who did not expect the cigarette reward outcome in the presence of the S+).",
            "output": [
                "Is drug expectancy necessary for stimulus control of human attention , instrumental drug-seeking behaviour and subjective pleasure?"
            ]
        },
        {
            "id": "task847-98fe2722e1a2464785c93e8060016ed8",
            "input": "Prostasin is downregulated in hormone-refractory prostate cancers (HRPC). The mechanisms by which androgens regulate prostasin expression are unclear.', 'LNCaP cells were treated with dihydrotestosterone (DHT), and mRNA expression of prostasin, SREBPs, SNAIL, and SLUG was examined by real-time PCR following reverse transcription. A human prostasin promoter was evaluated in HEK-293 cells co-transfected with transcription factor cDNAs. Regulation of endogenous prostasin expression by transfected SREBP-2 or SLUG was evaluated. Expression of SNAIL and SLUG mRNA in DU-145 cells treated with epidermal growth factor (EGF) was examined.', \"Prostasin mRNA expression in LNCaP cells was not responsive to DHT treatment. DHT marginally upregulated mRNA expression of SREBP-1c, SREBP-2, and SNAIL, but not SREBP-1a, while dramatically increased SLUG mRNA expression, in a dose-dependent manner. Co-transfection of prostasin promoter and SREBP cDNA in HEK-293 cells resulted in stimulation of promoter activity at approximately twofold by SREBP-1c, and up to sixfold by SREBP-2; while co-transfection with SNAIL or SLUG cDNA resulted in repression of promoter activity to 43% or 59%, respectively. Co-transfection of the SLUG cDNA negated SREBP-2's stimulation of prostasin promoter in a dose-dependent manner. Transfection of an SREBP-2 cDNA in HEK-293 and DU-145 resulted in upregulation of prostasin while transfection of a SLUG cDNA in LNCaP repressed prostasin expression. EGF upregulated SNAIL and SLUG mRNA in DU-145.",
            "output": [
                "Is androgen regulation of prostasin gene expression mediated by sterol-regulatory element-binding proteins and SLUG?"
            ]
        },
        {
            "id": "task847-0a23ed8efc944337a7966cfe548cda6d",
            "input": "Multiple diverse posttranslational modifications of alpha-tubulin such as detyrosination, further cleavage of the penultimate glutamate residue (Delta2-tubulin), acetylation, and polyglutamylation increase the structural and functional diversity of microtubules.', 'Herein, we characterized the molecular profile of alpha-tubulin posttranslational modifications in normal human prostate epithelial cells (PrEC), immortalized normal prostate epithelial cells (PZ-HPV-7), androgen-dependent prostate cancer cells (LNCaP), transitional androgen-independent prostate cancer cells (LNCaP-cds and CWR22Rv1), and androgen-independent prostate cancer cells (PC3).', 'Compared to PrEC and PZ-HPV-7 cells, all cancer cells exhibited elevated levels of detyrosinated and polyglutamylated alpha-tubulin, that was paralleled by decreased protein levels of tubulin tyrosine ligase (TTL). In contrast, PrEC and PZ-HPV-7 cells expressed markedly higher levels of Delta2-tubulin. Whereas alpha-tubulin acetylation levels were generally equivalent in all the cell lines, PC3 cells did not display detectable levels of Ac-tubulin.",
            "output": [
                "Do normal and prostate cancer cells display distinct molecular profiles of alpha-tubulin posttranslational modifications?"
            ]
        },
        {
            "id": "task847-a37d546d066642c08f798f7d83616c1d",
            "input": "PRV-1 mRNA is overexpressed by neutrophils from polycythemia vera patients and is homologous to NB1 a gene overexpressed in reactive neutrophilia.', 'These investigations were designed to confirm searches of genome databases suggesting that PRV-1 and NB1 are alleles of the same gene, CD177, and confirm a pseudogene adjacent to CD177. Methods included polymerase chain reaction (PCR), cloning, sequencing, and fluorescent hybridization studies.', 'The coding region of PRV-1 was PCR-amplified from human fetal RNA, cloned, and used to screen the RPCI-11 bacterial artificial chromosome (BAC) library. Five BACs were reactive with the PRV-1 probe. PCR analysis of the BACs with primers encompassing PRV-1 exons, containing four known single-nucleotide polymorphisms, followed by sequencing rendered amplicons identical to PRV-1 in all five BACs. Analysis of all five by restriction digestion yielded fragments possible only if both the gene and the pseudogene are present. End sequencing of the BACs localized them to the same chromosome region. G-banding and fluorescence in situ hybridization at the 400- and 850-band levels of resolution mapped one BAC to chromosome band 19q13.2 and sublocalized the BAC to band 19q13.31, respectively.",
            "output": [
                "Are the gene overexpressed in polycythemia rubra vera , PRV-1 , and the gene encoding a neutrophil alloantigen , NB1 , alleles of a single gene , CD177 , in chromosome band 19q13.31?"
            ]
        },
        {
            "id": "task847-bcc282ac48f8477899b34da6439af76e",
            "input": "Determine the influence of experience with consistent or inconsistent relationships between the sensory properties of snack foods and their caloric consequences on the control of food intake or body weight in rats.', 'Rats received plain and BBQ flavored potato chips as a dietary supplement, along with ad lib rat chow. For some rats the potato chips were a consistent source of high fat and high calories (regular potato chips). For other rats, the chips provided high fat and high calories on some occasions (regular potato chips) and provided no digestible fat and fewer calories at other times (light potato chips manufactured with a fat substitute). Thus, animals in the first group were given experiences that the sensory properties of potato chips were strong predictors of high calories, while animals in the second group were given experiences that the sensory properties of potato chips were not predictors of high calories.', 'Juvenile and adult male Sprague-Dawley rats.', 'Following exposure to varying potato chip-calorie contingencies, intake of a novel, high-fat snack food and subsequent chow intake were assessed. Body weight gain and body composition as measured by DEXA were also measured.', 'In juvenile animals, exposure to a consistent relationship between potato chips and calories resulted in reduced chow intake, both when no chips were provided and following consumption of a novel high-fat, high-calorie snack chip. Long-term experience with these contingencies did not affect body weight gain or body composition in juveniles. In adult rats, exposure to an inconsistent relationship between potato chips and calories resulted in increased consumption of a novel high-fat, high-calorie snack chip premeal along with impaired compensation for the calories contained in the premeal.",
            "output": [
                "Do consistent relationships between sensory properties of savory snack foods and calories influence food intake in rats?"
            ]
        },
        {
            "id": "task847-536f53f83cc54f1297742b2d3613896c",
            "input": "Fifteen human tissue kallikrein (KLK) genes have been identified as a cluster on chromosome 19. KLK expression is associated with various human diseases including cancers. Noncoding RNAs such as PCA3/DD3 and PCGEM1 have been identified in prostate cancer cells.', \"Using massively parallel signature sequencing (MPSS) technology, RT-PCR, and 5' rapid amplification of cDNA ends (RACE), we identified and cloned a novel gene that maps to the KLK locus.\", 'We have characterized this gene, named as KLK31P by the HUGO Gene Nomenclature Committee, as an unprocessed KLK pseudogene. It contains five exons, two of which are KLK-derived while the rest are \"exonized\" interspersed repeats. KLK31P is expressed abundantly in prostate tissues and is androgen regulated. KLK31P is expressed at lower levels in localized and metastatic prostate cancer cells than in normal prostate cells.",
            "output": [
                "Is kLK31P a novel androgen regulated and transcribed pseudogene of kallikreins that is expressed at lower levels in prostate cancer cells than in normal prostate cells?"
            ]
        },
        {
            "id": "task847-92df7fe51ca24cdcacbc123ccb5ada2e",
            "input": "Several compounds, including butyrate and trichostatin A, have been shown to activate gamma-gene expression via p38 mitogen-activated protein kinase (MAPK) signaling. In eukaryotic cells, reactive oxygen species (ROS) act as signaling molecules to mediate phosphorylation of tyrosine kinases such as p38 MAPK to regulate gene expression. Therefore, we determined the role of the reactive oxygen species hydrogen peroxide (H(2)O(2)) in drug-mediated fetal hemoglobin (HbF) induction.', \"H(2)O(2) levels were measured using 2',7'-dichlorofluorescein-diacetate in K562 cells after drug treatments. To confirm a role for H(2)O(2) in HbF induction, studies were completed with the mitochondrial respiratory chain inhibitor myxothiazole, which prevents ROS generation. The ability of myxothiazole to block gamma-globin mRNA accumulation and HbF induction was measured in K562 cells and burst-forming unit-erythroid colonies respectively using quantitative real-time PCR and alkaline denaturation.\", 'Butyrate and trichostastin A stimulated p38 MAPK phosphorylation via a H(2)O(2)-dependent mechanism. Pretreatment with myxothiazole to inhibit ROS formation or SB203580 to impede p38 MAPK signaling attenuated gamma-gene activation in K562 cells and HbF induction in erythroid progenitors. However, myxothiazole had no effect on the ability of hydroxyurea to induce HbF.",
            "output": [
                "Does fetal hemoglobin induction by histone deacetylase inhibitors involve generation of reactive oxygen species?"
            ]
        },
        {
            "id": "task847-9adf4b5b895847d8b6c1bfb1b3e7e41f",
            "input": "Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy.\", 'We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis.', 'CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 micromol/L, range 0.6-7.0). The concentration of CMMG was below the limit of quantification (<0.5 micromol/L) in asymptomatic subjects (P < 0.001). All patients with neuropsychiatric signs and symptoms, except one, had acute renal function impairment or chronic renal failure.",
            "output": [
                "Is the aciclovir metabolite CMMG detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment?"
            ]
        },
        {
            "id": "task847-027cc6db7c3449b0a712cff774a9ada0",
            "input": "A patient's baseline health status may affect the ability to survive an acute illness. Emergency medicine research requires tools to adjust for confounders such as comorbid illnesses. The Charlson Comorbidity Index has been validated in many settings but not extensively in the emergency department (ED). The purpose of this study was to examine the utility of the Charlson Index as a predictor of one-year mortality in a population of ED patients with suspected infection.\", 'The comorbid illness components of the Charlson Index were prospectively abstracted from the medical records of adult (age older than 18 years) ED patients at risk for infection (indicated by the clinical decision to obtain a blood culture) and weighted. Charlson scores were grouped into four previously established indices: 0 points (none), 1-2 points (low), 3-4 points (moderate), and > or =5 points (high). The primary outcome was one-year mortality assessed using the National Death Index and medical records. Cox proportional-hazards ratios were calculated, adjusting for age, gender, and markers of 28-day in-hospital mortality.', 'Between February 1, 2000, and February 1, 2001, 3,102 unique patients (96% of eligible patients) were enrolled at an urban teaching hospital. Overall one-year mortality was 22% (667/3,102). Mortality rates increased with increasing Charlson scores: none, 7% (95% confidence interval [CI] = 5.4% to 8.5%); low, 22% (95% CI = 19% to 24%); moderate, 31% (95% CI = 27% to 35%); and high, 40% (95% CI = 36% to 44%). Controlling for age, gender, and factors associated with 28-day mortality, and using the \"none\" group as a reference group, the Charlson Index predicted mortality as follows: low, odds ratio of 2.0; moderate, odds ratio of 2.5; and high, odds ratio of 4.7.",
            "output": [
                "Is charlson Index associated with one-year mortality in emergency department patients with suspected infection?"
            ]
        },
        {
            "id": "task847-11365224da124dba81a0cb70c0fbcf4b",
            "input": "Relatively little is known about why almost half of young adults in Australia have used cannabis. Because the upwards trend in use of cannabis has been coincident with an increase in marital breakdown, this study examines the relationship between marital status, marital changes, and the onset of cannabis use.', 'Data are from the Mater-University Study of Pregnancy (MUSP), a 21-year prospective study in Brisbane, Australia. The present study is based on the 3008 mothers and their children for whom there were complete follow-up data at 21 years. Outcomes were self-reported cannabis use at age 21 and early onset (before age 15) cannabis use as judged from a retrospective report obtained at 21 years. Analyses were conducted using multivariate binomial and multinomial logistic regression.', 'Change in maternal marital status when the child was aged between 5 and 14 years was significantly associated with increased risk of cannabis use [odds ratio (OR) = 1.7; 95% confidence interval (95% CI) 1.4-2.0 for one or two marital changes and OR = 2.3; 95% CI 1.5-3.4 for three or more marital changes], after adjustment for a range of potential confounders.",
            "output": [
                "Are changes in maternal marital status associated with young adults ' cannabis use : evidence from a 21-year follow-up of a birth cohort?"
            ]
        },
        {
            "id": "task847-b5aa4fc36c004cb4a077c1f19f773ab2",
            "input": "Chronic graft-vs-host disease (GVHD) has certain similarities with autoimmune diseases and is associated with the development of various autoantibodies in some patients. In this study, we analyzed the occurrence of autoantibodies in 63 patients surviving longer than 3 months after an allogeneic haematopoietic stem cell transplantation (HSCT), with the aim of detecting a possible association between occurrence of autoantibodies and development of chronic GVHD and immune recovery after HSCT.', 'The patients were screened every 3 months for the occurrence of the following autoantibodies: anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (ASMA), anti-cardiolipin (ACLA), anti-liver-kidney microsomal (LKM), anti-DNA, anti-neutrophil cytoplasmatic (ANCA), and anti-thyroid antibodies. Peripheral blood immunophenotyping with anti-CD3, CD4, CD8, CD19, CD20, CD16, and CD56 antibodies was evaluated at the same intervals.', 'Autoantibodies were not found in 18 patients (29%), at least in one screening in 29 patients (46%), and in all screenings in 16 patients (25%). ANA were found in 41 patients (65%), AMA in 4 (6%), ASMA in 4 (6%), ANCA in 7 (11%), ACLA in 1 (2%), anti-thyroid antibodies in 3 (5%), and anti-DNA in 2 (3%). More than one antibody occurred in 16/63 (25%) positive patients. ANA was significantly more frequent in patients with chronic GVHD and, among these, in those with the extensive form. The nucleolar pattern of immunofluorescence of ANA but not its titer was correlated with the extension of chronic GVHD. Patients who developed autoantibodies had higher CD20(+) cell blood counts than negative patients in the third month (p=0.006), ninth month (p=0.061), and twelfth month (p=0.043).",
            "output": [
                "Is the development of autoantibodies after allogeneic stem cell transplantation related with chronic graft-vs-host disease and immune recovery?"
            ]
        },
        {
            "id": "task847-643c4bb94d5945e7a2e71239f063d6a2",
            "input": "Nasal vaccination is an effective therapeutic regimen for preventing otitis media. Since cholera toxin (CT) is toxic, an alternative adjuvant is required for the development of a nasal vaccine. The efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined.', 'Mice were immunized intranasally with P6 protein of non-typeable Haemophilus influenzae (NTHi) and adjuvant, CT, or CpG ODN, and P6-specific antibody responses were examined. The expression of P6-specific cytokine mRNA in splenic CD4 T cells was also determined. In addition, NTHi challenges were performed and the NTHi was quantified in nasal washes.', 'P6-specific IgA in nasal wash and serum IgG titers were elevated significantly after nasal immunization. The IgG1/IgG2a ratio in serum from P6+CpG-immunized mice was less than that of P6+CT-immunized mice. Although IL-6 was expression similarly in both groups, IFN-gamma expression was greater in P6+CpG-immunized mice than in P6+CT-immunized mice. Enhanced clearance of NTHi from the nasopharynx was also shown equally in both groups.",
            "output": [
                "Does nasal vaccination with CpG oligodeoxynucleotide induce protective immunity against non-typeable Haemophilus influenzae in the nasopharynx?"
            ]
        },
        {
            "id": "task847-bd8e081c30d348c1af3bc86ec5a2a441",
            "input": "To identify the presence of side population (SP) cells in established head and neck squamous carcinoma cell (HNSCC) lines and to determine the role of EGFR in the regulation of the side population of these cells.', 'SP cells were identified using flow cytometry analysis by the ability of these cells to extrude the Hoechst 33342 dye via the drug transporter BCRP1/ABCG2. Effect of EGFR on the side population was determined also by difference in Hoechst extrusion and by immunofluorescence. Immunohistochemical staining was performed to show the presence of the BCRP1/ABCG2 transporter and the phosphorylated form of EGFR in HNSCC tissue.', 'SP cells are present in HNSCC cell lines. With the Hoechst 33342 extrusion assay, SP cells were found to comprise an average of 0.69% of the UMSCC10B cells and 0.91% of HN12 cells. Addition of the EGF ligand increased the SP population while inactivation of the EGFR kinase by Iressa significantly decreased SP.",
            "output": [
                "Does eGFR regulate the side population in head and neck squamous cell carcinoma?"
            ]
        },
        {
            "id": "task847-12ded0e7cc424b798673d713787f500c",
            "input": "To verify an impact of a lymph node revealing solution (LRS) on the number of lymph nodes (LN) revealed in colorectal resection specimens.', \"Fifty-nine cases of rectosigmoid carcinomas divided into two subgroups-stage pT2&3 (20 cases) and ypT2&3 (with pre-operative radiotherapy-39 cases)-were formalin fixed for 42-72 h, serially sectioned and re-fixed in LRS containing ethanol, diethyl ether, glacial acetic acid, and formalin for 24 h. The number of LNs was matched to a control group consisting of 34 cases of colorectal carcinoma, 14 pT2&3 and 20 ypT2&3 rectosigmoid carcinomas examined routinely. Results were statistically tested by Student's t-test.\", 'In the study group the total number of revealed LNs was 869, range 1-48, average 14.7 per specimen, median 15. In the control group the number of LNs was 200, range 0-13, average 5.9 per specimen, median 6. The difference between the study and the control group was statistically significant (P = 0.05).",
            "output": [
                "Is re-fixation in a lymph node revealing solution a powerful method for identifying lymph nodes in colorectal resection specimens?"
            ]
        },
        {
            "id": "task847-97cd151fbc0d46098b39190290caefed",
            "input": "Patients with MHI and a positive head computed tomography (CT) scan frequently have a routine repeat head CT (RRHCT) to identify possible evolution of the head injury requiring intervention. RRHCT is ordered based on the premise that significant injury progression may take place in the absence of clinical deterioration.', 'In a Level I urban trauma center with a policy of RRHCT, we reviewed the records of 692 consecutive trauma patients with Glasgow Coma Scale scores of 13-15 and a head CT (October 2004 through October 2005). The need for medical or surgical neurologic intervention after RRHCT was recorded. Patients with a worse and unchanged RRHCT were compared, and independent predictors of a worse RRHCT were identified by stepwise logistic regression.', 'There were 179 patients with MHI and RRHCT ordered. Of them, 37 (21%) showed signs of injury evolution on RRHCT and 7 (4%) required intervention. All 7 had clinical deterioration preceding RRHCT. In no patient without clinical deterioration did RRHCT prompt a change in management. A Glasgow Coma Scale score less than 15 (13 or 14), age higher than 65 years, multiple traumatic lesions found on first head CT, and interval shorter than 90 minutes from arrival to first head CT predicted independently a worse RRHCT.",
            "output": [
                "Is routine repeat head CT for minimal head injury unnecessary?"
            ]
        },
        {
            "id": "task847-1a64b3798b584edeb0ec9174d32781a0",
            "input": "To investigate the impact of disorders of arousal and sleep disturbance on everyday living and participation in rehabilitation.', 'Survey of rehabilitation centres based on naturalistic observation.', 'One hundred and thirty-five adults with acquired brain injury were reported by rehabilitation staff in seven centres across the UK for presence of arousal and/or sleep disturbance, the impact on rehabilitation and daily living and treatment strategies in use.', 'Disturbance of arousal or sleep patterns was reported in 47% of the sample, with significant adverse effect on activity evident in two-thirds of such cases. Prevalence of disordered arousal was consistent over time for up to 10 years post-injury. Concurrent psychiatric illness, but not epilepsy, was associated with arousal and sleep disorder. Non-pharmacological interventions and benzodiazepine/hypnotic drugs were in use in 34% and 20% of cases respectively. In all cases of prescribed hypnotic drugs, period of use exceeded recommended UK guidelines.",
            "output": [
                "Is rehabilitation compromised by arousal and sleep disorders : results of a survey of rehabilitation centres?"
            ]
        },
        {
            "id": "task847-0bae6bedc70d4bbeb1d89f3927fac6d6",
            "input": "While it is well-known that there is 18F-FDG uptake in breast tumors, clinical impact of (18)F-FDG PET in managing breast cancer patients is not well-studied.', 'One hundred and thirty-three consecutive breast cancer patients from May 1996 to June 2000 were studied. All patients were treated and being followed. Reasons of referral included equivocal conventional studies, staging/re-staging, clinical suspicion of recurrence, and elevated serum tumor markers. Clinical status at 6 months postPET is used as the gold standard in lesions of worsening versus stable or improving.', 'PET was 69% sensitive and 80% specific in predicting clinical stage at 6 months. This 69% of the patients who got worse at 6 months was PET positive and 80% of the patients who were stable or improving at 6 months were PET negative. There was a significant association between PET results and clinical outcome, after adjusting for stage of disease (P=0.04), or for the treatment patients received (P<0.01). Negative PET results changed therapy as often as positive ones did. PET influenced treatment decisions in 74% of the patients referred for study.",
            "output": [
                "Does a retrospective analysis of the impact of 18F-FDG PET scan on clinical management of 133 breast cancer patients?"
            ]
        },
        {
            "id": "task847-b0fa9c1425514b44a1ef97c543e70e74",
            "input": "Congenital glaucoma is primarily a surgical disease with medical management serving as a temporizing measure before surgery or as postoperative adjunctive treatment. First-line surgery for congenital glaucoma consists of incisional procedures on the anterior chamber angle: goniotomy and trabeculotomy. Angle surgery has a high success rate with few complications. Despite the high initial success rate, almost 20% of angle procedures eventually fail, and surgeons are confronted with a choice of what procedure to do next: a trabeculectomy with or without adjunctive antifibrosis therapy, glaucoma drainage surgery, or cyclodestructive procedures. This review will discuss and compare these procedures as reported in recent studies and how variables such as age, number of prior procedures, and type of glaucoma have clarified the order in which these procedures might be performed after failed angle surgery.', 'Clinical reports in refractory pediatric glaucoma consist solely of retrospective studies of varying size and quality. Recent studies of trabeculectomy in this population suggest mitomycin C is associated with increased risk of late infectious complications. Trabeculectomy has worse outcome among younger patients Glaucoma drainage devices have a success rate approaching 80% at 1 year, but less with longer follow-up. Cyclodestructive procedures are generally reserved for advanced cases, but low-dose cyclodiode therapy and endocyclophotocoagulation may prove useful earlier in the disease (< 2 years).",
            "output": [
                "Does options in pediatric glaucoma after angle surgery have failed?"
            ]
        },
        {
            "id": "task847-1650a21369d6437381a29a3d8dd9e4fb",
            "input": "The magnitude and duration of postprandial blood glucose elevation seem to be important risk factors for diabetes Type 2 and coronary heart disease. AIM.: To investigate whether post-meal light physical activity might reduce the blood glucose increase.', 'Nine young (18-25 years) and 10 middle-aged (45-65 years) sedentary women, and 10 young and 10 middle-aged trained women participated in a meal/physical activity trial. Commencing after an overnight fast, each subject participated in two experiments, carried out on separate days: Day 1, the subjects were given cornflakes (1 g carbohydrate per kg body weight) to be ingested during 15 min. Blood glucose was determined while resting, before meal, and each 15 min for the next 120 min. Day 2 was similar to Day 1 but included light bicycling exercise for 30 min after finishing the meal.', 'In all trials, irrespective of age and training condition, light bicycling for 30 min after the carbohydrate meal blunted the rise in blood glucose.",
            "output": [
                "Does postprandial light physical activity blunt the blood glucose increase?"
            ]
        },
        {
            "id": "task847-60977fea93b2436193cde03116092666",
            "input": "Monitoring plasma gentamicin concentrations in neonates 24 hours after a once daily dose (4 mg/kg) often necessitates additional blood sampling. In adults a nomogram has been developed enabling evaluation of gentamicin doses by sampling concentrations with other blood tests, 4-16 hours after administration. We attempted to develop a similar nomogram for neonates.', 'In addition to standard 24 hour sampling to monitor trough concentrations, one additional \"random\" gentamicin concentration was measured in each of 50 neonates < 4 days of age (median gestation 33 weeks [28-41]), when other blood samples were clinically necessary, 4-20 hours after gentamicin administration. 24 hour concentrations of > 1 mg/L were considered high, and an indication to extend the dosing interval.', 'Highest correlation (r2 = 0.51) of plasma gentamicin concentration against time (4 to 20 hours) was with logarithmic regression. A line drawn 0.5 mg/L below the true regression line resulted in all babies with 24 hr gentamicin concentrations > 1 mg/L having the additional \"random\" test result above that line, i.e. 100% sensitivity for 24 hour concentrations > 1 mg/L, though only 58% specificity. Having created the nomogram, 39 further babies (median gestation 34 weeks [28-41]), were studied and results tested against the nomogram. In this validation group, sensitivity of the nomogram for 24 hr concentrations > 1 mg/L was 92%; specificity 14%, positive predictive value 66%, and negative predictive value 50%. Prematurity (< or = 37 weeks) was a more sensitive (94%) and specific (61%) indicator of high 24-hour concentrations. 62 (87%) of 71 preterm babies had high 24-hour concentrations.",
            "output": [
                "Do `` Random '' gentamicin concentrations predict trough levels in neonates receiving once daily fixed dose regimens?"
            ]
        },
        {
            "id": "task847-22d1702542dd4f0e8e26cc0cf8f4f47f",
            "input": "CD40L was found to reduce doxorubicin-induced apoptosis in non Hodgkin's lymphoma cell lines through caspase-3 dependent mechanism. Whether this represents a general mechanism for other tumor types is unknown.\", \"The resistance induced by CD40L against apoptosis induced by a panel of cytotoxic chemotherapeutic drugs in non Hodgkin's lymphoma and breast carcinoma cell lines was investigated.\", \"Doxorubicin, cisplatyl, etoposide, vinblastin and paclitaxel increased apoptosis in a dose-dependent manner in breast carcinoma as well as in non Hodgkin's lymphoma cell lines. Co-culture with irradiated L cells expressing CD40L significantly reduced the percentage of apoptotic cells in breast carcinoma and non Hodgkin's lymphoma cell lines treated with these drugs. In breast carcinoma cell lines, these 5 drugs induced an inconsistent increase of caspase-3/7 activity, while in non Hodgkin's lymphoma cell lines all 5 drugs increased caspase-3/7 activity up to 28-fold above baseline. Co-culture with CD40L L cells reduced (-39% to -89%) the activation of caspase-3/7 induced by these agents in all 5 non Hodgkin's lymphoma cell lines, but in none of the 2 breast carcinoma cell lines. Co culture with CD40L L cells also blocked the apoptosis induced by exogenous ceramides in breast carcinoma and non Hodgkin's lymphoma cell lines through a caspase-3-like, 8-like and 9-like dependent pathways.",
            "output": [
                "Does cD40L induce multidrug resistance to apoptosis in breast carcinoma and lymphoma cells through caspase independent and dependent pathways?"
            ]
        },
        {
            "id": "task847-633b8b64bc1b4709950a84f4d755de57",
            "input": "To determine the stunning effect of a tracer dose of 5 mCi iodine-131.', 'We retrospectively analyzed 145 patients who received the first ablative treatment at our service. Patients were divided according to disease status determined upon post-treatment scanning (101 patients with thyroid remnants and 44 with pulmonary metastases) and whole-body scanning before ablation (performed on 69 individuals). All patients with thyroid remnants were treated with an ablative dose of 100 mCi and those with metastases received 200 mCi.', 'In patients with remnants only (n= 41) or metastases (n= 28) submitted to diagnostic scanning, uptake was found to be apparently increased in most patients cases (71 and 73%, respectively) 7 days after therapy, while reduced uptake (visual) was not observed in any patient. The efficacy of ablation was similar in the groups submitted or not to diagnostic scanning: 71 and 80% in patients without metastases (p= 0.28), respectively, and 43 and 50% in those with pulmonary involvement (p= 0.64).",
            "output": [
                "Does 5 mCi pretreatment scanning cause stunning when the ablative dose is administered within 72 hours?"
            ]
        },
        {
            "id": "task847-83e85b754710486fa5825ffc29685717",
            "input": "To examine the utility of four criteria for distinguishing aortic from mitral valve prostheses on supine anteroposterior (AP) chest x rays in critically ill patients.', 'Two reviewers independently examined the post operative chest X-rays (CXR) of all patients undergoing either an aortic or mitral valve replacement over a 32 month period, in a blinded fashion. They applied four criteria to each film. For each criterion a sensitivity and specificity of differentiating the valve positions correctly was calculated for each reviewer, as well as a kappa statistic for inter-observer agreement between the two reviewers.', \"Two hundred and twenty seven CXR's were evaluated by each of the reviewers. There were 174 aortic and 53 mitral valve replacements. There was a high level of inter-observer agreement for all four criteria applied (kappa values 0.785 to 0.966). Criterion one (imaginary line method) could be applied by both reviewers to less than 50% of CXR's, and when applied was specific but not sensitive. The other three criteria could be applied by both reviewers to approximately 80% of films. Criterion 2 (orientation method) was sensitive but not specific. Criteria 3 (valve orifice method) and 4 (perceived direction of blood flow method) were both highly sensitive and specific and are therefore the best methods.",
            "output": [
                "Is the imaginary line method reliable for identification of prosthetic heart valves on AP chest radiographs?"
            ]
        },
        {
            "id": "task847-9887040a7fa1421193e35e96b3e5959a",
            "input": "This study describes three options for postnatal care in Sweden and contains a cost analysis of the options in various combinations. The aim of the study was to calculate the cost of a postnatal care model according to new parents' preferences.\", 'Staff costs were calculated for various models of postnatal care, comprising the maternity ward, the family suite, and/or the early discharge program. One of the models was based on answers from 342 parents who specified their preferences with regard to postnatal care in the event of another birth.', 'Comparing costs for five different models of postnatal care showed that the proportion of mothers receiving care at the maternity ward crucially influences the total costs. The staff costs differed significantly between the models, ranging from US$448 000 to US$778 000 per 1500 mother-child dyads.', \"Cost calculation of various care models and parents' preferences for postnatal care.",
            "output": [
                "Is satisfying parents ' preferences with regard to various models of postnatal care cost-minimizing?"
            ]
        },
        {
            "id": "task847-36032803547c4d50b8010b4c6655a8ca",
            "input": "This study examines the influence of surgical management (elimination of the infectious focus and abdominal lavage) on survival and the inflammatory response in the various compartments of the body: local (abdomen), systemic (blood) and distant organ (lungs).', 'Peritonitis was established in mice by cecal ligation and puncture (CLP). After 24 h, a group was made in which the infected cecum was resected and the abdominal cavity was lavaged (RES), and another group that received no surgical resection (NoRES). Survival was examined over a period of 96 h. Mice were sacrificed at 24 (sham and CLP), 48 and 72 h after CLP to measure inflammatory parameters.', 'Survival was significantly lower is NoRES compared to sham and RES (p = 0.006, p = 0.014, respectively). Intraperitoneal parameters were improved in the RES group compared to sham but results were not significantly different between groups. In plasma, levels of interleukin-6 (IL-6) were decreased in RES (p = 0.048). Accordingly, anti-inflammatory IL-10 in plasma was increased in this group (p = 0.031). In the lung, keratinocyte-derived chemokine (KC) and myeloperoxidase (MPO) was reduced indicating decreased granulocytes accumulation in the lung in the RES group (p = 0.012 and p = 0.004, respectively).",
            "output": [
                "Does surgical therapy attenuate abdominal and extra-abdominal inflammation in experimental peritonitis?"
            ]
        },
        {
            "id": "task847-f631c59d56134440ad3e43efcc839ab8",
            "input": "No information exists regarding whether a favorite television category choice affects attention, memory, or cognition among older women.', 'Cross-sectional data from a population-based community sample of 289 older cognitively and physically intact women who were surveyed about television use. The cognitive battery included measures of psychomotor speed, executive attention, immediate and delayed verbal memory, and global cognition.', 'Talk shows (P < 0.05) or soap operas (P < 0.05) as a favorite television category were consistently associated with poorer scores on all cognitive outcomes in both unadjusted and adjusted analyses. Clinically significant cognitive impairment across domains were associated with watching talk shows (OR = 7.3; 95% CI = 1.9, 28.4) and soap operas (OR = 13.5; 95% CI = 3.7, 49.5).",
            "output": [
                "Are soap operas and talk shows on television associated with poorer cognition in older women?"
            ]
        },
        {
            "id": "task847-0973c30bf9354045bee5a505b9959dff",
            "input": "Considering the epileptogenic effect of cavernoma-surrounding hemosiderin, assumptions are made that resection only of the cavernoma itself may not be sufficient as treatment of symptomatic epilepsy in patients with cavernous malformations. The purpose of this study was to test the hypothesis whether seizure outcome after removal of cavernous malformations may be related to the extent of resection of surrounding hemosiderin-stained brain tissue.', 'In this retrospective study, 31 consecutive patients with pharmacotherapy-refractory epilepsy due to a cavernous malformation were included. In all patients, cavernomas were resected, and all patients underwent pre- and postoperative magnetic resonance imaging (MRI). We grouped patients according to MRI findings (hemosiderin completely removed versus not/partially removed) and compared seizure outcome (as assessed by the Engel Outcome Classification score) between the two groups.', 'Three years after resection of cavernomas, patients in whom hemosiderin-stained brain tissue had been removed completely had a better chance for a favorable long-term seizure outcome compared with those with detectable postoperative hemosiderin (p=0.037).",
            "output": [
                "Is seizure outcome after resection of cavernous malformations better when surrounding hemosiderin-stained brain also is removed?"
            ]
        },
        {
            "id": "task847-f239515e95ad45e3960cd71074cfde7d",
            "input": "Human inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis), is associated with leukocyte accumulation in the inflamed intestinal tissue. Recent studies strongly suggest a role of beta1 integrin receptors in regulating tissue damage and disease symptoms related to inflammatory bowel disease. The aim of this study was to investigate the role of the collagen-binding alpha2beta1 integrin (CD49b/CD29) in dextran sodium sulfate-induced colitis in mice.\", 'Colitis was induced in mice through oral administration of 2% dextran sodium sulfate in drinking water. Rectal administration of anti-alpha2-monoclonal antibody (mAb) in 1 group was compared with oral treatment with betamethasone in another group and rectal administration of a control antibody in a third group. Clinical and histological signs of colitis, neutrophil infiltration into the colon mucosa, and gene expression of metalloproteinases were assessed.', 'Rectal administration of anti-alpha2-mAb was found to significantly reduce weight loss from 13.5% +/- 6.5% to 2.2% +/- 0.2% (P = 0.013 versus control mAb) and mucosal neutrophil infiltration from 47.2 +/- 10.0 to 6.6 +/- 8.0 neutrophils per counted area (P < 0.05 versus control mAb). Metalloproteinase gene expression was suppressed through anti-alpha2-mAb treatment. The protective effect against colitis seen after anti-alpha2beta1 integrin treatment was found to be favorable to the effect seen after high-dose oral betamethasone.",
            "output": [
                "Does integrin alpha2beta1 regulate neutrophil recruitment and inflammatory activity in experimental colitis in mice?"
            ]
        },
        {
            "id": "task847-a6c1379b79674cc3bd6c41de4044c9c1",
            "input": "Molecular evolutionary analysis based on coalescent theory can provide important insights into epidemiologic processes worldwide. This approach was combined with analyses of the hepatitis C virus (HCV) epidemiologic-historical background and HCV-related hepatocellular carcinoma (HCC) in different countries.', 'The HCV gene sequences of 131 genotype 1b (HCV-1b) strains from Japan, 38 HCV-1a strains from the United States, 33 HCV-1b strains from Spain, 27 HCV-3a strains from the former Soviet Union (FSU), 47 HCV-4a strains from Egypt, 25 HCV-5a strains from South Africa, and 24 HCV-6a strains from Hong Kong isolated in this study and previous studies were analyzed.', 'The coalescent analysis indicated that a transition from constant size to rapid exponential growth (spread time) occurred in Japan in the 1920s (HCV-1b), but not until the 1940s for the same genotype in Spain and other European countries. The spread time of HCV-1a in the United States was estimated to be in the 1960s; HCV-3a in the FSU, HCV-5a in South Africa, and HCV-6a in Hong Kong in the 1960s, mid-1950s, and late 1970s, respectively. Three different linear progression curves were determined by analysis of the relationship between HCV seroprevalence and HCC mortality in different geographic regions; a steep ascent indicated the greatest progression to HCC in Japan, a near horizontal line indicated the least progression in the United States and the FSU, and an intermediate slope was observed in Europe.",
            "output": [
                "Does molecular tracing of the global hepatitis C virus epidemic predict regional patterns of hepatocellular carcinoma mortality?"
            ]
        },
        {
            "id": "task847-242a9226fafc4823bb5c159d230021b0",
            "input": "Data by [Bell et al. J Psychopharmacol (2002) 16:5-14] suggest that a decrease in 5-HT neurotransmission predisposes to panic attacks and that the antipanic effect of SSRIs depends upon the availability of 5-HT in the brain.', 'Our aim was to assess the effect of acute tryptophan depletion (TD) on cholecystokinin-tetrapeptide (CCK-4)- induced symptoms in patients with panic disorder (PD) who had responded to a 10-week treatment with a selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram.', 'A total of 18 patients (6 males and 12 females, mean age 34.5 years) received a tryptophan-free amino acid drink and a control drink, each followed by a CCK-4 challenge (25 microg), 1 week apart in a double-blind crossover design.', 'The results showed no significant differences in response to the CCK-4 challenge between the TD and the control conditions. Panic rate after the CCK-4 challenge was 27.8% after depletion and 33.3% after control drink (chi2=0.13, p=0.72). No significant effects of TD were observed in panic intensity scores, subjective anxiety, or cardiovascular indices.",
            "output": [
                "Does tryptophan depletion modify response to CCK-4 challenge in patients with panic disorder after treatment with citalopram?"
            ]
        },
        {
            "id": "task847-1c063228004b42c694b08026283fbedb",
            "input": "We sought to define the mechanisms and correlates of leptin's vascular actions in humans with coronary artery disease.\", \"In 131 patients (age 65.7+/-0.7 years mean+/-SEM), ex vivo vascular reactivity to leptin (10(-13)-10(-7) M) was assessed in saphenous vein (SV) rings. Leptin led to SV relaxation (maximal relaxation 24.5+/-1.6%). In separate experiments, relaxation to leptin was unaffected by L-NMMA (17.4+/-3.4 vs.17.8+/-3.3%, P = 0.9) or endothelial denudation (17.4+/-4.4 vs. 22.5+/-3.0%, P = 0.4). We explored the possibility that leptin's vascular effects are mediated via smooth muscle hyperpolarization. In the presence of KCl (30 mmol/L) to inhibit hyperpolarization, the vasodilator effect of leptin was completely blocked (0.08+/-4.1%, P < 0.001 vs. control). Similar results were demonstrated in internal mammary artery rings. The only independent correlate of leptin-mediated vasodilatation was plasma TNF-alpha (r = 0.25, P < 0.05). Neither body mass index nor waist circumference correlated with leptin-mediated vasorelaxation. This lack of a correlation with markers of total body fat/fat distribution suggests that leptin resistance may not extend to the vasculature.",
            "output": [
                "Is leptin an endothelial-independent vasodilator in humans with coronary artery disease : Evidence for tissue specificity of leptin resistance?"
            ]
        },
        {
            "id": "task847-ccec4922b4154d02be2c2b0b8f7070ef",
            "input": "To determine whether or not serum adiponectin concentrations are influenced by ovarian hyperstimulation during in vitro fertilization (IVF).', 'This study involved 52 women who were participating in IVF-ET cycles. Adiponectin levels in serum were determined by radioimmunoassay and compared.', 'Serum adiponectin levels fell from Day-basal to Day-hCG (p = 0.047), and then rose on Day-OR and again on Day-7ET (p < 0.001; p < 0.001). Estradiol levels on Day-hCG were significantly and positively correlated with serum adiponectin levels on Day-OR and Day-7ET (r = 0.325, p = 0.019; r = 0.372, p = 0.007). Progesterone levels on Day-OR positively correlated with serum adiponectin levels on Day-basal (r = 0.278, p = 0.046). There was also a positive correlation between progesterone levels on Day-7ET and serum adiponectin levels on Day-OR (r = 0.289, p = 0.038). Multiple linear regression analysis revealed that adiponectin levels on Day-OR and Day-7ET were negatively correlated with age and body mass index after adjustment was made for concomitant diseases.",
            "output": [
                "Do serum adiponectin levels increase after human chorionic gonadotropin treatment during in vitro fertilization?"
            ]
        },
        {
            "id": "task847-02ad507713ad49aca0a398a75f2c54a5",
            "input": "Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by the presence of eosinophils and neutrophils. However, the mechanisms that mediate the influx of these cells are incompletely understood. Neutrophil products, including neutrophil elastase and antimicrobial peptides such as neutrophil defensins and LL-37, have been demonstrated to display chemotactic activity towards cells from both innate and adaptive immunity. However, chemotactic activity of LL-37 towards eosinophils has not been reported. Therefore, the aim of the present study was to investigate the chemotactic activity of LL-37 for eosinophils and to explore the mechanisms involved in LL-37-mediated attraction of neutrophils and eosinophils.', 'Neutrophils and eosinophils were obtained from venous blood of healthy donors. Chemotaxis was studied using a modified Boyden chamber technique. Involvement of formyl-peptide receptors (FPRs) was studied using the antagonistic peptide tBoc-MLP. Activation of the mitogen-activated protein kinase (MAPK) ERK1/2 was studied by Western blotting using antibodies directed against phosphorylated ERK1/2.', 'Our results show that LL-37 chemoattracts both eosinophils and neutrophils. The FPR antagonistic peptide tBoc-MLP inhibited LL-37-induced chemotaxis. Whereas the FPR agonist fMLP activated ERK1/2 in neutrophils, LL-37 did not, indicating that fMLP and LL-37 deliver different signals through FPRs.",
            "output": [
                "Is human cathelicidin LL-37 a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors?"
            ]
        },
        {
            "id": "task847-d9583513181b4b7d90e4d24ff9dfab1e",
            "input": "We investigated whether age-related macular degeneration risk factors are associated with high-sensitivity C-reactive protein (CRP) and homocysteine (HCY), systemic biomarkers for cardiovascular disease.', 'Subjects with a range of age-related macular maculopathies or no maculopathy at two centers in the United States were evaluated. Risk factors and biomarkers were assessed by questionnaire, direct measurement, or analyses of blood specimens.', 'Higher levels of serum antioxidants vitamin C and lutein/zeaxanthin and higher fish intake were associated with lower serum CRP levels, whereas serum vitamin E, smoking, and increased body mass index were associated with increased CRP. Serum vitamin E, serum alpha-carotene, and dietary intake of antioxidants and vitamin B6 were associated with lower levels of plasma HCY, whereas hypertension was associated with increased HCY.",
            "output": [
                "Are c-reactive protein and homocysteine associated with dietary and behavioral risk factors for age-related macular degeneration?"
            ]
        },
        {
            "id": "task847-87f69f8a23fc4215b2ddee9ff17d3d0e",
            "input": "The current paradigm suggests that matrix metalloproteinase 9 (MMP-9) expressed by stromal cells is a therapeutic target in human colorectal tumors which presumably regulates metastatic disease progression. Conversely, whereas cancer cells within those tumors may induce stromal cells to produce MMP-9 and may be targets for MMP-9 activity, they are not the source of MMP-9 underlying metastasis.', 'MMP-9 expression in matched colorectal tumors and normal adjacent mucosa from patients and human colon cancer cell lines was examined by real-time reverse transcription-PCR, laser capture microdissection, immunoelectron microscopy, and immunoblot analysis. The role of colon cancer cell MMP-9 in processes underlying metastasis was explored in vitro by examining degradation of extracellular matrix components by gelatin zymography and formation of locomotory organelles by cell spreading analysis and in vivo by quantifying hematogenous tumor cell seeding of mouse lungs.', 'Primary colorectal tumors overexpress MMP-9 compared with matched normal adjacent mucosa. In contrast to the current paradigm, MMP-9 is expressed equally by cancer and stromal cells within human colon tumors. Cancer cell MMP-9 regulates metastatic behavior in vitro, including degradation of extracellular matrix components and formation of locomotory organelles. Moreover, this MMP-9 critically regulates hematogenous seeding of mouse lungs by human colon cancer cells in vivo.",
            "output": [
                "Is tumor epithelial cell matrix metalloproteinase 9 a target for antimetastatic therapy in colorectal cancer?"
            ]
        },
        {
            "id": "task847-fbc59ffbfae74e5dae0565a509aedbd9",
            "input": "The 6-min walk test (6MWT) has prognostic value in various pulmonary disorders including idiopathic pulmonary fibrosis (IPF). We determined the individual prognostic accuracy of distance walked and oxygen saturation during the 6MWT in patients with IPF. We defined a new composite index, the distance-saturation product (DSP), which is the product of distance walked and lowest oxygen saturation during the 6-min walk test. We compared the performance of the DSP to the individual 6MWT parameters in predicting mortality.', 'We evaluated pulmonary function tests, 6-min walk parameters and the DSP between survivors and non-survivors. The ability of each measure to discriminate outcomes was determined by receiver operator curves.', '81 patients (48 survivors, 33 non-survivors) were included. Pulmonary function tests were similar and did not correlate with survival. Desaturation was greater (89.4% versus 83.7%, P<0.001) and distance walked was lower (406.9 versus 181.3m, P = 0.005) in non-survivors. The DSP was significantly lower among non-survivors (364.8 versus 153.5m%, P < 0.001) and predicted mortality more accurately than either individual 6MWT component (P = 0.035 versus desaturation, P=0.040 versus distance). A DSP <200 m% was associated with a seven-fold greater risk of 12-month mortality and an 18.0% shorter median survival compared with a DSP > 200 m% (P < 0.001).",
            "output": [
                "Does the distance-saturation product predict mortality in idiopathic pulmonary fibrosis?"
            ]
        },
        {
            "id": "task847-635baf070b724d1bb2e07edb4be237c0",
            "input": "Several studies have reported that ventriculoperitoneal shunt insertion for treatment of normal-pressure hydrocephalus results in improvement of gait and, less frequently, improvement of cognition. We sought to identify the demographic factors associated with cognitive improvement after shunt insertion to improve assessment of prognosis for cognitive gains with treatment.', 'We report cognitive testing before and after ventriculoperitoneal shunt insertion in 36 patients with normal pressure hydrocephalus, who previously had improvement of any clinical symptom--gait, urinary incontinence, cognition--after a diagnostic trial of continuous cerebrospinal fluid drainage.",
            "output": [
                "Do demographic factors influence cognitive recovery after shunt for normal-pressure hydrocephalus?"
            ]
        },
        {
            "id": "task847-64fd215622cb4360a976282fdcbd6ac5",
            "input": "Dihydrofolate reductase (DHFR) and thymidylate synthase (TS) are crucial enzymes in DNA synthesis. In alveolata both enzymes are expressed as one bifunctional enzyme.', \"Loss of this essential enzyme activities after successful allelic assortment of knock out alleles yields an auxotrophic marker in ciliates. Here the cloning, characterisation and functional analysis of Tetrahymena thermophila's DHFR-TS is presented. A first aspect of the presented work relates to destruction of DHFR-TS enzyme function in an alveolate thereby causing an auxotrophy for thymidine. A second aspect is to knock in an expression cassette encoding for a foreign gene with subsequent expression of the target protein.",
            "output": [
                "Does the bifunctional dihydrofolate reductase thymidylate synthase of Tetrahymena thermophila provide a tool for molecular and biotechnology applications?"
            ]
        },
        {
            "id": "task847-bfeb68ad5def457b9485d9c6c49e6eb8",
            "input": "Elevated adrenal androgen levels are common in polycystic ovary syndrome (PCOS), but the underlying pathogenetic mechanism is poorly understood. In the rare cortisone reductase deficiency, impaired regeneration of active cortisol from inert cortisone by 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) results in compensatory activation of ACTH secretion and adrenal hyperandrogenism. 11beta-HSD1 deficiency may protect against obesity and its metabolic consequences because of impaired regeneration of cortisol in adipose tissue.', 'Our objective was to investigate a functional polymorphism in HSD11B1 (T-->G in the third intron rs12086634, which associates with lower 11beta-HSD1 activity) in PCOS with and without obesity.', 'We conducted a case-control study in lean and obese PCOS patients and controls at an academic hospital.', 'Participants included 102 Caucasian PCOS patients and 98 controls comparable for age, weight, and race.', 'We assessed genotype distribution and influence of genotypes on clinical, hormonal, and metabolic parameters.', 'The G allele was significantly related to PCOS status (P = 0.041), and this association was mainly attributable to lean (P = 0.025), rather than obese (P = 0.424), PCOS patients. The G allele was associated with lower 0800-0830 h plasma cortisol (P < 0.001) and higher cortisol response to ACTH(1-24) (P < 0.001) in all women with PCOS and with higher dehydroepiandrosterone sulfate levels (P < 0.001), greater suppression of dehydroepiandrosterone sulfate by dexamethasone (P < 0.001), and lower fasting plasma low-density lipoprotein cholesterol (P = 0.002) levels in lean PCOS women.",
            "output": [
                "Does genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predict adrenal hyperandrogenism among lean women with polycystic ovary syndrome?"
            ]
        },
        {
            "id": "task847-fca648f153014fdc8c2b2df5173ad9ee",
            "input": "We examined the immediate effect of a systemic nitric oxide augmentation on the bladder outlet resistance in healthy men.', 'Eleven healthy male volunteers with a mean age of 25.5 yr were included in the study. They were prepared for a standard urodynamic study, and a baseline pressure-flow study was obtained. The subjects were then given 20 mg isosorbide dinitrate sublingually, and after refilling their bladder a second pressure-flow study was done after 20 min. The pressure-flow studies were then compared in regard to the average flow rate, the average detrusor pressure during micturition, and the detrusor pressure at maximum flow rate.', 'One of the subjects was unable to void and had to be excluded from the study. In the remaining 10 men, the mean average flow rate increased from 16.7 ml/s before to 20.2 ml/s after the intake of the NO donor (P=0.013). Concomitantly, the average detrusor pressure during micturition decreased from a mean of 57 to 52 cm H2O (P=0.004) and the mean detrusor pressure at maximum flow rate decreased from 60 to 52 cm H2O (P=0.013).",
            "output": [
                "Does systemic nitric oxide augmentation lead to a rapid decrease of the bladder outlet resistance in healthy men?"
            ]
        },
        {
            "id": "task847-18f00aaf252b41a989d75edec7a1b6ad",
            "input": "We are conducting clinical vaccine trials with the HER2/neu peptide, E75, in patients with breast cancer. The purpose of this study was to demonstrate clonal expansion of E75-specific CD8(+) T cells and to identify intra- and interantigenic epitope spreading.', 'Pre- and postvaccination peripheral blood leukocyte samples (24 node positive [NP] and 20 node negative [NN]) from 44 vaccinated patients were analyzed. HLA-A2:Ig dimer molecules were loaded with the HER2 peptides, E75 or GP2, and were used with anti-TcR and CD8 antibodies to stain peripheral blood leukocyte immediately ex vivo and were analyzed with flow cytometry. In 8 randomly selected patients, dimers were loaded with the folate binding protein peptide E41 to evaluate for interantigenic epitope spreading.', 'All patients with NP and 95% of the patients with NN showed E75-specific clonal expansion. Patients with NN showed more robust expansion. All patients with NP and 85% of the patients with NN showed evidence of intra-antigenic epitope that was spreading to GP2. However, patients with NN showed only moderate expansion to this subdominant epitope, which was not included in the immunizing mix. The degree of HER2/neu expression and disease stage impacted the ability to expand clonally E75- and GP2-specific CD8(+) T cells. Evidence of interantigenic epitope spreading to E41 was shown in 63% of the patients who were tested.",
            "output": [
                "Does vaccination with a HER2/neu peptide induce intra- and inter-antigenic epitope spreading in patients with early stage breast cancer?"
            ]
        },
        {
            "id": "task847-a5669f2b20e94c9f82f133408b8fddbc",
            "input": "DNA transcription is regulated, in part, by acetylation of nuclear histones that are controlled by 2 groups of enzymes: histone deacetylases (HDAC) and histone acetyl transferases (HAT). Whether an imbalance in HDAC/HAT system plays a role in hemorrhage/resuscitation is unknown. The goals of this study were to determine whether hemorrhage results in deacetylation of cardiac histones and whether this can be corrected through the application of different resuscitation strategies or specific HDAC inhibitors.', \"In the first experiment, rats (n = 6 per group) were subjected to volume-controlled hemorrhage and resuscitated with racemic lactated Ringer's solution, L-lactated Ringer's solution, 7.5% hypertonic saline solution, ketone Ringer's solution, and pyruvate Ringer's solution. Control groups included no hemorrhage (sham) and hemorrhage with no resuscitation. In the second experiment (n = 5 per group), 3 HDAC inhibitors (valproic acid, trichostatin A, and suberoylanilide hydroxamic acid) were added to saline solution resuscitation. Heart tissue was collected at the end of resuscitation. Isolated subcellular protein fractions were used in Western blotting to analyze the patterns of total protein acetylation and histone acetylation specifically. HDAC and HAT activity was measured in tissue extracts.\", \"Hemorrhage led to partial histone deacetylation. Resuscitation resulted in protein hyperacetylation in nuclear fractions only. A detailed analysis of histones (on 10 acetylation sites) revealed that ketone Ringer's solution hyperacetylated histones H2B, H3, and H4. The addition of suberoylanilide hydroxamic acid hyperacetylated histones more effectively than other resuscitation strategies, presumably by direct inhibition of HDAC activity.",
            "output": [
                "Are cardiac histones substrates of histone deacetylase activity in hemorrhagic shock and resuscitation?"
            ]
        },
        {
            "id": "task847-57e3162069f64f9f912d18543db67192",
            "input": "Plants achieve remarkable plasticity in shoot system architecture by regulating the activity of secondary shoot meristems, laid down in the axil of each leaf. Axillary meristem activity, and hence shoot branching, is regulated by a network of interacting hormonal signals that move through the plant. Among these, auxin, moving down the plant in the main stem, indirectly inhibits axillary bud outgrowth, and an as yet undefined hormone, the synthesis of which in Arabidopsis requires MAX1, MAX3, and MAX4, moves up the plant and also inhibits shoot branching. Since the axillary buds of max4 mutants are resistant to the inhibitory effects of apically supplied auxin, auxin and the MAX-dependent hormone must interact to inhibit branching.', 'Here we show that the resistance of max mutant buds to apically supplied auxin is largely independent of the known, AXR1-mediated, auxin signal transduction pathway. Instead, it is caused by increased capacity for auxin transport in max primary stems, which show increased expression of PIN auxin efflux facilitators. The max phenotype is dependent on PIN1 activity, but it is independent of flavonoids, which are known regulators of PIN-dependent auxin transport.",
            "output": [
                "Does the Arabidopsis MAX pathway control shoot branching by regulating auxin transport?"
            ]
        },
        {
            "id": "task847-69afe017c0cd4c11ad33c0ed303a90c3",
            "input": "To compare the efficacy of an enteric-coated buffered pancreatic enzyme (EC buffered PE) containing 1.5 mEq of bicarbonate per capsule with a conventional enteric-coated enzyme (EC-PE) capsule in cystic fibrosis patients with signs or symptoms of moderate to severe malabsorption.', 'In a double-blind crossover study, subjects were randomly assigned to two consecutive, 2-week phases using an EC buffered PE product and conventional EC-PE product. Seventy-two hour stool collections from each phase were analyzed for energy, fat, and nitrogen content and expressed as percent of estimated intake.', 'Twenty-one patients with cystic fibrosis and pancreatic insufficiency (14 female, mean age 20.6 +/- 11.5 years, range 8.8-41.9) completed the study. There was no significant difference in percent malabsorption of energy (19.4% vs. 19.0%), fat (20.7% vs. 20.2%), or nitrogen (10.4% vs. 10.7%) between the EC buffered PE product and the conventional EC-PE product. However, patients taking the EC buffered PE product received less enzyme based on actual enzyme activity measured in vitro (3,468 +/- 1,434 U lipase/g fat vs. 3,978 +/- 1,474 U lipase/g fat, P < 0.02).",
            "output": [
                "Is enteric-coated pancreatic enzyme with bicarbonate equal to standard enteric-coated enzyme in treating malabsorption in cystic fibrosis?"
            ]
        },
        {
            "id": "task847-f6e9144a571c498fabde0bc07f46d434",
            "input": "There have been investigations on the chemopreventive effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in gastric cancer and also on the association between cyclo-oxygenase 2 expression and the clinicopathological features of gastric cancer. However, it is not yet clear whether the cardioprotective properties of low-dose aspirin could affect the biological behavior of gastric cancer. This study was aimed at investigating the association between the use of low-dose aspirin and clinicopathological features of gastric cancer in human.', 'A case-control study was performed retrospectively by comparing the clinicopathological parameters between two groups of gastric cancers, 47 (30.5%) low-dose aspirin users and 107 (69.5%) non-aspirin users who were diagnosed and underwent operation for gastric cancers.', 'The gastric cancers of aspirin user group showed favorable clinicopathological features, such as earlier tumor stage (overall stage, T and N stage: p < 0.001, <0.001, and 0.002, respectively), smaller size (p = 0.03), and intestinal type rather than diffuse type (p = 0.004). But these differences were significant only in non-cardiac cancer while cardiac cancer patients showed no significant association with low-dose aspirin usage (overall stage, T stage, N stage, tumor size, and histological type: p <0.001, <0.001, 0.003, 0.035, and 0.004, respectively, by Cochran-Mantel-Haenszel statistics).",
            "output": [
                "Does low-dose aspirin affect the clinicopathological features of gastric cancer?"
            ]
        },
        {
            "id": "task847-14d6139d678a4a1690e7db91442df382",
            "input": "Relapse to drug-seeking in abstinent heroin addicts and reinstatement in experimental animals are observed when exposed to drug-associated stimuli or cues, the drug itself, and stressful events. It has been shown that footshock-induced stress increases the rewarding effects of opiates, delays extinction, and induces the reinstatement of drug-seeking. However, the effects of social stress on the reinstatement of opiate-seeking after extinction has not been studied.', 'The role of physical (restraint and tail pinch) and social (social defeat) stressors on the reinstatement of morphine-induced conditioned place preference (CPP) was evaluated.', 'Adult male OF1 mice were conditioned with 10, 20, or 40 mg/kg of morphine or saline. Only morphine-conditioned animals acquired CPP. All mice underwent extinction sessions until the CPP was extinguished. Then, the effects of physical or social stress on the reinstatement of CPP were evaluated. Morphine- and saline-conditioned animals were exposed to the respective stressor or control stress condition immediately or 15 min before reinstatement tests. In experiment 1, animals underwent restraint for 15 min. In experiment 2, animals were exposed to tail pinch or placed in a cage without any manipulation for 15 min. In experiment 3, animals performed an agonistic encounter with an isolated or anosmic mouse or were placed in a cage without any social contact or manipulation.', 'Restraint, tail pinch, and social defeat in an agonistic encounter with an isolated mouse produce the reinstatement of CPP in morphine-conditioned animals.",
            "output": [
                "Is social stress as effective as physical stress in reinstating morphine-induced place preference in mice?"
            ]
        },
        {
            "id": "task847-1870224b68bb41698085c5b49f80ee78",
            "input": "Recent psychopharmacological studies lend support to the notion of partially dissociable neuronal systems dedicated to processing specific emotions. For example, GABA-ergic enhancement after an acute dose of the benzodiazepine, diazepam, produces specific impairments in anger and fear recognition. However, it is unclear if these impairments are a general property of benzodiazepines and other drugs that produce a similar profile of neurocognitive impairment to benzodiazepines, such as the anticholinergic, scopolamine.', 'We investigated the effects of scopolamine and the benzodiazepine, lorazepam, on emotion-recognition accuracy.', 'A double-blind independent group design was used with 48 healthy volunteers to compare the effects of scopolamine and lorazepam with an inactive placebo on a commonly used emotion-recognition task. Control measures included an episodic memory task and subjective mood ratings.', 'Anger and disgust recognition accuracy was impaired after scopolamine. In contrast, lorazepam produced no impairment in emotion-recognition despite producing similar levels of sedation and anterograde amnesia to scopolamine.",
            "output": [
                "Does scopolamine induce impairments in the recognition of human facial expressions of anger and disgust?"
            ]
        },
        {
            "id": "task847-63ba2c4062e249d791b1593446349927",
            "input": "To determine the real association between serum lipid levels and colonic polyp formation.', 'We performed a large scale retrospective study to analyze the correlation between the incidence of colorectal adenoma or carcinoma and the fasting serum levels of total cholesterol (TC) and triglycerides (TG) in patients who underwent total colonoscopy for screening for colon cancer.', 'Both levels were significantly elevated in patients with adenomas as compared with patients without any neoplastic lesion (TC 207.6+/-29.5 vs 199.5+/-34.3, n=4883, P<0.001; TG 135.0+/-82.2 vs 108.7+/-71.5, n=4874, P<0.001). The difference was significant in patients with tubular adenoma but not in those with villous or serrated adenoma. Multiple logistic regression analysis including age and sex revealed that TG was an independent correlation factor in male (P<0.01), but not in female patients. The level of TG in patients with invasive carcinoma did not show a significant elevation from that in patients with adenoma. These findings suggest that hypertriglyceridemia is an independent risk factor for colonic adenoma in men.",
            "output": [
                "Is hypertriglyceridemia positively correlated with the development of colorectal tubular adenoma in Japanese men?"
            ]
        },
        {
            "id": "task847-b62d830317f24ce8ae0bf61a82071e63",
            "input": "In chronic renal failure leptin levels are elevated and BMD decreased, however, so far data about correlations between leptin and BMD in dialyzed patients are scarce. It has been suggested that leptin is a predictor of BMD in postmenopausal women. We examined the relationships between leptinemia, BMD and bone metabolism in HD and CAPD patients. We also assessed whether leptin is significant and independent predictor of BMD in dialyzed patients.', 'BMD was measured using dual energy X-ray absorptiometry (DEXA) at lumbar spine and femoral neck in 25 HD and 23 CAPD patients. Markers of bone turnover and leptin were studied using commercially available kits.', 'In femoral neck BMD was significantly higher in CAPD patients, without significant differences in BMD in lumbar spine. There was a negative correlation between BMD at the femoral neck and time on hemodialysis (r= -0.45, p < 0.05). In CAPD patients BMD at the lumbar spine correlated negatively with vitamin D3 (r= -0.54, p < 0.05), osteocalcin (r= 0.54, p < 0 .05), and positively with BMI (r= 0.63, p < 0.01). BMD at the femoral neck correlated positively with BMI (r= 0.59, p < 0.01), and negatively with osteocalcin (r= -0.63, p < 0.05) and time on CAPD (r= -0.52, p < 0.05). Leptin correlate only with cholesterol (r= 0.25, p < 0.05), TSH (r= 0.35, p < 0.01), ss(2) microglobulin (r= 0.32, p < 0.001) and BMD at the femoral neck (r= -0.23, p < 0.05)in all dialyzed (HD and CAPD) patients.",
            "output": [
                "Are bone mineral density and bone metabolism related to leptin in hemodialyzed and peritoneally dialyzed uremic patients?"
            ]
        },
        {
            "id": "task847-9aaa834532c04ef0af722b469104c51c",
            "input": "The 460Trp allele of the alpha-adducin gene (ADD1), which is involved in a form of salt-sensitive hypertension, has been associated with patterns of target organ damage.', 'As carotid artery intima-media thickness (IMT) largely depends upon unknown genetic factors, besides being associated to conventional risk factors, we tested the association of the 460Trp allele of ADD1 with IMT in a well-characterized sample of young healthy normotensive subjects, to assess the role of ADD1 polymorphism without overlapping effects of age or already elevated blood pressure.', 'Anthropometric measurements, blood pressure (BP), and carotid artery wall IMT (high-resolution sonography and digitalized morphometry) were obtained in 420 healthy normotensive Caucasian university students. Genotypes for ADD1 were detected by automated genomic polymerase chain reaction (PCR).', 'ADD1 genotypes were evenly distributed between genders. IMT was significantly larger in carriers of the 460Trp allele of ADD1, while a significant gender x ADD1 interaction (P = 0.02) demonstrated that IMT was increased only in males carrying the 460Trp allele (P < 0.001). No significant association was found in females.",
            "output": [
                "Does the 460Trp allele of alpha-adducin increase carotid intima-media thickness in young adult males?"
            ]
        },
        {
            "id": "task847-f4b62e41c5ca486f98cb0241b49d8180",
            "input": "We previously showed that fibromuscular dysplasia (FMD) of the renal artery may be familial. Case reports have associated alpha1-antitrypsin deficiency and FMD. The aim of this study was to test the implication of the alpha1-antitrypsin (AAT) gene in a large cohort of patients with renal FMD.', 'A case-control study comparing the genotype frequencies in 161 consecutive patients with angiographically proven renal FMD with those observed in three sets of controls (353 hypertensive patients, 288 normotensive patients, 444 normotensive women) was conducted. High-resolution echotracking of the carotid and radial arteries was performed in a subset of 77 FMD patients. Three functional polymorphisms of the AAT gene (PiM1, PiZ, PiS) were investigated.', 'Clinical (age 44.3 +/- 13.8 years, 85.1% women) and radiological (77.1% of multifocal lesions) characteristics of the FMD population were consistent with those previously published. No differences were found in AAT genotype frequencies in the FMD subjects compared with the 1085 controls. We found no correlation between the AAT genotypes and the clinical and angiographical characteristics of the FMD patients. Echotracking results confirmed our previously published results in FMD patients with a specific pattern and a mean arterial phenotypic score greater than 3. However, no difference in the arterial score was observed across the genotypes.",
            "output": [
                "Are alpha1-antitrypsin gene polymorphisms associated with renal arterial fibromuscular dysplasia?"
            ]
        },
        {
            "id": "task847-4639e52d5ce54a7a8e4b3a631797a92a",
            "input": "The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors.', 'In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction].', 'Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001).",
            "output": [
                "Is high-sensitivity C-reactive protein only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors?"
            ]
        },
        {
            "id": "task847-cdd003d116e14b5ab3d6ee666f6e1fe7",
            "input": "Smoking is an important risk factor for cardiovascular disease. Sympathetic responses to cigarette smoking may be implicated in the link between smoking and cardiovascular disease. We tested the hypothesis that the sympathetic neural responses to smoking are age dependent.', 'We examined the effects of cigarette smoking and sham smoking on muscle sympathetic nerve activity, blood pressure and heart rate in 14 normotensive middle-aged (49 +/- 4 years) and 12 young (29 +/- 4 years) habitual smokers matched for body mass index (25 +/- 2 kg/m2 in both groups).', 'Sham smoking had no significant effect on sympathetic drive, blood pressure or heart rate in either group. Cigarette smoking increased heart rate in both middle-aged subjects and young subjects. In comparison to younger subjects, middle-aged smokers showed similar smoking-related increases in systolic blood pressure (SBP) [10 +/- 3 versus 12 +/- 2 mmHg, respectively, not significant (NS)]. Smoking decreased sympathetic nerve activity by 28 +/- 12% of baseline values (P < 0.01) in young subjects. However, muscle sympathetic nerve activity did not change significantly after smoking in middle-aged subjects (5 +/- 8%, NS), despite the increased blood pressures, which would be expected to inhibit sympathetic activity. By contrast, in young subjects, the heart rate increase (22 +/- 2 bpm) was greater than that seen in middle-aged subjects (13 +/- 2 bpm, P < 0.01).",
            "output": [
                "Are sympathetic neural responses to smoking age dependent?"
            ]
        },
        {
            "id": "task847-f42d8deb27884eb88aab4c9c4e849889",
            "input": "Nasopharyngeal carcinoma (NPC) poses one of the serious health problems in southern Chinese, with an incidence rate ranging from 15 to 50/100,000. In our previously linkage analysis, a locus on 3p21 was identified to link to NPC. In this study, family-based association analysis was performed to test the transmission disequilibrium of chromosome 3p in 18 high-risk nasopharyngeal carcinoma families of Hunan province in southern China.', 'Single locus and multi-point of transmission disequilibrium test was performed by Genehunter program package with 15 microsatellite markers on chromosome 3p in 18 nasopharyngeal carcinoma pedigrees.', 'A major transmission disequilibrium peak was observed near D3S1568, which possessed 20 alleles or haplotypes of 6 loci, spanning a 12.4 cM region from D3S1298 to D3S1289 on chromosome 3p21.31-3p21.2, and 3 alleles or haplotypes reached high significantly difference (P < 0.01).",
            "output": [
                "Does family-based association analysis validate chromosome 3p21 as a putative nasopharyngeal carcinoma susceptibility locus?"
            ]
        },
        {
            "id": "task847-eebae3a38e004096b77c489f1ddeb7b4",
            "input": "Telomerase preserves telomere length and structure, preventing cellular senescence, which is associated with alteration of the chromosomal ends. We hypothesized that telomerase activity is altered in peripheral blood mononuclear cells (PBMCs) of hemodialysis (HD) patients. To investigate this hypothesis as well as the relationship between telomerase and inflammation, we measured the activity of this reverse transcriptase as well as the level of several inflammatory markers in PBMCs and serum of an end-stage renal failure (ESRF) population and a non-renal-failure group of subjects.', 'In PBMCs isolated from 42 HD and 39 non-renal-failure subjects of the same age (51.0 +/- 12.4 and 51.4 +/- 12.1 years, respectively) telomerase activity was measured using PCR-ELISA; the method was based on the telomeric repeat amplification protocol.', 'Telomerase activity in PBMCs was detected in 18 (42.9%) HD and 28 (71.8%) non-renal-failure subjects (p = 0.013). Among positive subjects, percent telomerase activity in PBMCs was significantly higher in non-renal- failure (117 +/- 112 %) than in HD (47.6 +/- 57.1 %) subjects (p = 0.008). Detectable telomerase activity was lower in long-term than in short-term HD patients (13.3 +/- 8.9 vs. 75.0 +/- 64.8%, respectively, p = 0.015). Although higher in HD group, inflammatory indexes (C-reactive protein, interleukin-6, IL-6, soluble IL-6 and soluble gp130) were not correlated to telomerase activity in PBMCs.",
            "output": [
                "Is telomerase activity decreased in peripheral blood mononuclear cells of hemodialysis patients?"
            ]
        },
        {
            "id": "task847-54c22028a3c7421c8ad6379f137bc761",
            "input": "Burns cause thermal injury to local tissue and trigger systemic acute inflammatory processes, which may lead to multiple distant organ dysfunction. We investigated the protective effect of dietary whey supplementation on distant organs in a rat model.', 'Forty-eight rats were divided into six groups of eight: groups 1 and 2 were the controls, fed a standard diet and a whey-supplemented diet, respectively; groups 3 and 4 were fed a standard diet and subjected to burn injury; and groups 5 and 6 were fed a whey-supplemented diet and subjected to burn injury. We measured the oxidative stress variables, as well as glutathione in the liver and kidney, and histologically examined skin samples obtained 4 h (groups 3 and 5) and 72 h (groups 4 and 6) after burn injury.', 'Glutathione (GSH) levels remained the same in the liver but were slightly elevated in the kidneys after burn injury in the rats fed a standard diet. Whey supplementation caused a significant increase in hepatic GSH levels 4 h after burn injury. Moreover, there was a significant rebound effect in the liver and kidney GSH levels after 72 h and whey supplementation potentiated this effect. Hepatic and renal lipid peroxide levels were also increased 4 h after burn injury in the rats fed a standard diet. Whey supplementation significantly suppressed the burn-induced increase in hepatic and renal lipid peroxide levels. Histological examination revealed that although whey supplementation resulted in decreased subepidermal inflammation, the indicators of wound healing and collagen deposition were not improved.",
            "output": [
                "Does whey feeding suppress the measurement of oxidative stress in experimental burn injury?"
            ]
        },
        {
            "id": "task847-fcc7585dd94d4598b3c3fb8bdfc52bbc",
            "input": "Activin A and inhibin A have been found to be elevated in women without diabetes subsequently developing pre-eclampsia. The aim was to investigate whether activin A and inhibin A in serum were elevated in type I diabetic women after developing pre-eclampsia and, if so, were they clinically useful as predictors of pre-eclampsia.', 'In a prospective study, maternal serum was analyzed for activin A and inhibin A in 115 women with type 1 diabetes at 10, 14, 22, 28, and 33 weeks of gestation.', 'Fourteen women (12%) developed pre-eclampsia (26-37 weeks of gestation) and 101 did not. The two groups were comparable regarding age, body mass index, and diabetes duration. There was no difference between serum concentrations of activin A and inhibin A in women developing pre-eclampsia and women who did not at any gestational period.",
            "output": [
                "Are serum levels of activin A and inhibin A related to the increased susceptibility to pre-eclampsia in type I diabetic pregnancies?"
            ]
        },
        {
            "id": "task847-75a164b13cd74edea76af06027698f71",
            "input": "Evidence suggests that delayed re-endothelialization is responsible for in-stent thrombosis. Probucol inhibits neointimal thickening in animals via enhanced re-endothelialization and is the only oral drug that consistently inhibits restenosis after coronary angioplasty in humans. Here, we examined the effects of probucol on re-endothelialization and neointimal formation in a stent model.', 'New Zealand White rabbits were fed a hypercholesterolemic diet with probucol (1%) or without (control) (n=11 each) for 6 weeks. At 2 weeks, endothelial denudation and stenting of the iliac artery was performed. Iliac arteries were harvested at week 6, and stented segments sectioned and analyzed. Compared with control, probucol increased in-stent re-endothelialization (74+/-6% in controls versus 93+/-3% in probucol-treated; P=0.008), and decreased average luminal stenosis (58+/-27 versus 31+/-16%; P=0.01) and stent depth (619+/-310 versus 314+/-158 microm; P=0.009). Compared with control, probucol also decreased accumulation of macrophages in the neointima. Furthermore, none of the probucol-treated rabbits had in-stent thrombosis, whereas four of eleven control rabbits showed thrombosis (P=0.04).",
            "output": [
                "Does probucol inhibit in-stent thrombosis and neointimal hyperplasia by promoting re-endothelialization?"
            ]
        },
        {
            "id": "task847-c30dbd0595664fe4bddad915e598b5b0",
            "input": "There is a growing appreciation of the role that nasal mucosa plays in innate immunity. In this study, the expression of pattern recognition receptors known as toll-like receptors (TLRs) and the effector molecules complement factor 3 (C3), properdin, and serum amyloid A (SAA) were examined in human sinonasal mucosa obtained from control subjects and patients with chronic rhinosinusitis (CRS).', 'Sinonasal mucosal specimens were obtained from 20 patients with CRS and 5 control subjects. Messenger RNA (mRNA) was isolated and tested using Taqman real-time polymerase chain reaction with primer and probe sets for C3, complement factor P, and SAA. Standard polymerase chain reaction was performed for the 10 known TLRs. Immunohistochemistry was performed on the microscopic sections using antibodies against C3.', 'Analysis of the sinonasal sample mRNA revealed expression of all 10 TLRs in both CRS samples and in control specimens. Expression of the three effector proteins was detected also, with the levels of mRNA for C3 generally greater than SAA and properdin in CRS patients. No significant differences were found in TLR or innate immune protein expression in normal controls. Immunohistochemical analysis of sinonasal mucosal specimens established C3 staining ranging from 20 to 85% of the epithelium present.",
            "output": [
                "Are serum amyloid A , properdin , complement 3 , and toll-like receptors expressed locally in human sinonasal tissue?"
            ]
        },
        {
            "id": "task847-cda6c3bd48fd497b8a159a0905a45621",
            "input": "To determine expression of cell cycle and apoptotic genes, biochemical analysis of CCL23 and antisense cyclin D1-transfected CCL23 (CCL23AS) cells in the presence of cisplatin was performed. In addition, biochemical analysis of CAL27 cells before and after treatment with cisplatin was performed to determine expression of cell cycle genes.', 'CCL23, CCL23AS, and CAL27 cell lines were treated with cisplatin. Western blot analysis, fluorescence-activated cell sorting, and apoptosis assays were performed.', 'In vitro study of head and neck cancer cell lines CCL23, CCL23AS, and CAL27.', 'CCL23, CCL23AS, and CAL27 cells were treated with cisplatin.', 'Expression of p16, p21, p53, Bcl-xL, Bcl-xS, p27, DP1, MDM2, Bcl-2, c-Jun, and Jun-D were assessed using Western blot analysis.', 'There was increased expression of p16, p21, p53, BCLxL, and BCLxS genes with cisplatin treatment in the CCL23 and CCL23AS cells. Expression of p27, DP1, MDM2, BCL2, c-iun, and jun-D remained unaltered after treatment. There was decreased phosphorylation of Rb protein with complete absence of hyperphosphorylated Rb in the maximally sensitized antisense cyclin D1-transfected (CCL23AS) cells. Fluorescence-activated cell sorter analysis revealed a decreased G2 phase of the cell cycle and an increased proportion of apoptotic cells in the CCL23AS cell line compared with parental CCL23 cells. Cell killing also occurred in the presence of caspase-3 inhibitor. While CCL23 cells contain wild-type p53, the CAL27 cells have a point mutation in codon 193 (A-->T transversion) of exon 6. However, CAL27 cells still exhibited increased expression of p21 after treatment with cisplatin.",
            "output": [
                "Does cisplatin-induced growth arrest of head and neck cancer cells correlate with increased expression of p16 and p53?"
            ]
        },
        {
            "id": "task847-7cc7a1dbf5044067bf92f0ea8af86f1c",
            "input": "The combination of systemic multiagent chemotherapy (5-fluorouracil + cisplatin) and tumor irradiation is standard of care for head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been shown that sublethal doses of radiation or chemotherapeutic drugs in diverse cancer types may alter the phenotype or biology of neoplastic cells, making them more susceptible to CTL-mediated cytotoxicity. However, little is known about the potential synergistic effect of drug plus radiation on CTL killing. Here, we examined whether the combination of two chemotherapeutics and ionizing radiation enhanced CTL-mediated destruction of HNSCC more so than either modality separately, as well as the basis for the enhanced tumor cell lysis.', 'Several HNSCC cell lines with distinct biological features were treated with sublethal doses of cisplatin and 5-fluorouracil for 24 hours and with 10-Gy irradiation. Seventy-two hours postirradiation, tumor cells were exposed to an antigen-specific CD8+ CTL directed against carcinoembryonic antigen or MUC-1.', 'In three of three tumor cell lines tested, enhanced CTL activity was observed when the two modalities (chemotherapy and radiation) were combined as compared with target cells exposed to either modality separately. CTL-mediated lysis was MHC restricted and antigen specific and occurred almost entirely via the perforin pathway. Moreover, the combination treatment regimen led to a 50% reduction in Bcl-2 expression whereas single modality treatment had little bearing on the expression of this antiapoptotic gene.",
            "output": [
                "Does combination chemotherapy and radiation of human squamous cell carcinoma of the head and neck augment CTL-mediated lysis?"
            ]
        },
        {
            "id": "task847-8f0268e39a734c8b8131fae870832132",
            "input": "Participation rates in colorectal cancer (CRC) screening are rather low. We evaluated the interest of first degree relatives (FDR) of CRC patients to participate in a colonoscopy screening and compared the findings to controls with a negative family history.', 'There were 235 CRC patients diagnosed in our centre in 1984-2001. These were mailed an invitation letter for a preventive examination for their FDR older than 40 years and a questionnaire about occurrence of malignancies in their family. Colonoscopy was performed in 52 FDR and sex/age matched controls.', 'The questionnaire was delivered to 196 patients. Thirty four (17.3%) patients responded. Positive family history for CRC was reported in 12/34 (35.3%) patients, compared to expected 3.4 patients (p = 0.04; OR 4.2; 95% CI = 1.05-17.89). Fifty two of 94 (55.3%) FDR participated in a screening and CRC was diagnosed in 2 and CRA in 18 patients compared to 1 CRC and 9 CRA in control group (p = 0.04; Kaplan-Meier p = 0.04).",
            "output": [
                "Does positive family history promote participation in colorectal cancer screening?"
            ]
        },
        {
            "id": "task847-bb599c6a8ff54f5c98374521d8bde8ad",
            "input": "To describe the long-term outcomes of cases of neovascular glaucoma drained by Molteno implants.', 'A prospective study of 145 eyes (130 patients) followed up for a mean of 3.3 years (range, 0.02 year [5 days] to 18.1 years) in the province of Otago, New Zealand, from 1979 to 2002.', 'Insertion of a Molteno implant controlled the intraocular pressure at 21 mm Hg or less with a probability (95% confidence interval) of 0.72 (0.64-0.80), 0.60 (0.51-0.69), and 0.40 (0.29-0.50) at 1, 2, and 5 years, respectively. Failure to control intraocular pressure at 1, 2, and 5 years was significantly correlated with persistent iris neovascularization (P<.001, P<.001, and P = .01, respectively). Visual acuity at final follow-up in nonenucleated eyes was maintained or improved in 56 eyes (39%) and deteriorated to light perception or better in 25 (17%) or no light perception in 47 (32%). Seventeen eyes (12%) were enucleated.",
            "output": [
                "Do long-term results of Molteno implant insertion in cases of neovascular glaucoma?"
            ]
        },
        {
            "id": "task847-adaac2adb83f4bb0bf3d540315921d72",
            "input": "Results of the Women's Health Initiative Memory Study (WHIMS) raised concerns regarding the timing and formulation of hormone interventions. Conjugated equine estrogens (CEE), used as the estrogen therapy in the WHIMS trial, is a complex formulation containing multiple estrogens, including several not secreted by human ovaries, as well as other biologically active steroids. Although the full spectrum of estrogenic components present in CEE has not yet been resolved, 10 estrogens have been identified. In the present study, we sought to determine which estrogenic components, at concentrations commensurate with their plasma levels achieved following a single oral dose of 0.625 mg CEE (the dose used in the WHIMS trial) in women, are neuroprotective and whether combinations of those neuroprotective estrogens provide added benefit. Further, we sought, through computer-aided modeling analyses, to investigate the potential correlation of the molecular mechanisms that conferred estrogen neuroprotection with estrogen interactions with the estrogen receptor (ER).\", 'Cultured basal forebrain neurons were exposed to either beta-amyloid(25-35) or excitotoxic glutamate with or without pretreatment with estrogens followed by neuroprotection analyses. Three indicators of neuroprotection that rely on different aspects of neuronal damage and viability, LDH release, intracellular ATP level and MTT formazan formation, were used to assess neuroprotective efficacy. Results of these analyses indicate that the estrogens, 17alpha-estradiol, 17beta-estradiol, equilin, 17alpha-dihydroequilin, equilinen, 17alpha-dihydroequilenin, 17beta-dihydroequilenin, and Delta8,9-dehydroestrone were each significantly neuroprotective in reducing neuronal plasma membrane damage induced by glutamate excitotoxicity. Of these estrogens, 17beta-estradiol and Delta8,9-dehydroestrone were effective in protecting neurons against beta-amyloid25-35-induced intracellular ATP decline. Coadministration of two out of three neuroprotective estrogens, 17beta-estradiol, equilin and Delta8,9-dehydroestrone, exerted greater neuroprotective efficacy than individual estrogens. Computer-aided analyses to determine structure/function relationships between the estrogenic structures and their neuroprotective activity revealed that the predicted intermolecular interactions of estrogen analogues with ER correlate to their overall neuroprotective efficacy.",
            "output": [
                "Are select estrogens within the complex formulation of conjugated equine estrogens ( Premarin ) protective against neurodegenerative insults : implications for a composition of estrogen therapy to promote neuronal function and prevent Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-1c70ce8b944a491a9ecfc16abf2f77ed",
            "input": "Data on combined permanent atrial fibrillation (pAF) surgery and coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) are scarce, and the mid- and long-term effects on survival and cardiac rhythm are unknown.', 'In a prospective analysis 125 patients (Group I: CABG and/or AVR, n = 50; Group II: mitral valve [MV] surgery, n = 75) with pAF (> or = 6 months) underwent either concomitant monopolar (Group I: n = 20; Group II: n = 75) or bipolar (Group I: n = 30) radiofrequency (RF) ablation procedures. Group I patients had a significantly smaller left atrial (LA) size than Group II patients (LA-diameter: 47.7 +/- 4.6 vs. 58.2 +/- 6.1 mm; p < 0.01). Regular follow-up was performed from 3 to 36 months after surgery to assess survival, NYHA-class, and conversion rate to stable sinus rhythm (SR).', 'Early mortality (< 30 days) of Group I patients was 0% (Group II: 2.7%), cumulative survival at long-term follow-up was 0.95 vs. 0.82 (p = 0.31) and NYHA-class improved significantly in both groups, particularly in cases with stable SR. At follow-up 80% of Group I patients had SR (Group II: 70%). In Group I patients the bipolar approach was associated with significantly shorter ablation procedure times compared to the monopolar procedure (12.1 +/- 3.4 vs. 18.9 +/- 1.6 min; p < 0.05).",
            "output": [
                "Is permanent atrial fibrillation ablation surgery in CABG and aortic valve patients at least as effective as in mitral valve disease?"
            ]
        },
        {
            "id": "task847-e95a31c5587748908afc706df1d9f24c",
            "input": "To investigate the expression of cyclooxygenase (COX)-1, -2, and -3 RNA and protein in retinal pigment epithelial (ARPE-19) cells and in human neural (HN) cells exposed to the stress-inducing cytokines IL-1beta and TNF-a, the oxidizing peroxide H(2)O(2), the combination of TNF-alpha + H(2)O(2), and the lipofuscin fluorophore A2E.', 'Three-week-old ARPE-19 and HN cells were incubated with IL-1beta (10 ng/ml), TNF-alpha (10 ng/ml), H(2)O(2) (0.6 microM), TNF-alpha + H(2)O(2) (10 ng/ml and 0.6 microM), or A2E (10 microM) for 8 hr, after which total RNA and whole cellular proteins were isolated. Cyclooxygenase-1, -2, and -3 RNA and protein levels were quantified using Northern and Western immunoassay.', 'IL-1beta-, H(2)O(2)-, TNF-alpha-, TNF-alpha + H(2)O(2)-, or A2E-stressed ARPE-19 or HN cells displayed no significant upregulation in COX-1 or COX-3 RNA message abundance; however, significant upregulation was observed in COX-2 RNA message and protein abundance. A2E treatment of HN cells resulted in modest increases in COX-3 protein, an effect that was not observed in ARPE-19 cells.",
            "output": [
                "Does a2E selectively induce cox-2 in ARPE-19 and human neural cells?"
            ]
        },
        {
            "id": "task847-467148f10ee84244a69bf20e0919cdd4",
            "input": "The purpose of this study was to examine the effectiveness of ankle bracing and taping in preventing recurrencess of ankle sprains, specifically in female athletes.', \"Varsity soccer players' medical records over a five-year period were retrospectively reviewed at a Division III women's college. Data were extracted regarding any history of ankle sprain(s), type of intervention used as prophylaxis after the ankle sprain, number of exposures, and any incidence of recurrence.\", 'All collegiate varsity soccer players who had suffered a previous sprain to either one or both ankles (38 players) were identified as subjects.', 'Each previously injured ankle (n = 56) was considered as a case for the analysis. Ankles that had a previous sprain received one of four interventions: 1) a canvas, laced ankle brace (n = 19), 2) taping (n = 12), 3) a combination of taping and ankle bracing (n = 8), or 4) no treatment (n = 17).', 'The four intervention groups had a total of 1717 practice exposures and 650 competitive game exposures; exposures did not differ among the 4 groups. Ankle sprain recurrence frequency was 0%, 25%, 25%, and 35% for the braced, taped, combination, and untreated groups, respectively. The recurrence incidence for the braced group was significantly lower than that of the other three groups. The ankle sprain recurrence frequency did not differ among the taped, combination, and no treatment groups.",
            "output": [
                "Does ankle brace effectively reduce recurrence of ankle sprains in female soccer players?"
            ]
        },
        {
            "id": "task847-6c350ead23b3412998b01b7a0fc06e3f",
            "input": "To investigate the mechanisms for the cytopathic effect (CPE) of human cytomegalovirus (HCMV) in ECV304 endothelial-like cells.', 'PCR and indirect immunofluorescence were used to detect HCMV infection by examining immediate-early (IE) gene and protein expression of the virus in ECV304 cells. Phase-contrast and electron microscopies were performed to observe the morphological changes of the infected and uninfected cells, and DNA ladder analysis and flow cytometry were carried out to study HCMV-induced cell apoptosis.', 'In HCMV-infected ECV304 cells, cytopathic effects were first observed at approximately 72 h post-infection. The cells with CPE changes exhibited detachment from the monolayer, cell rounding and shrinkage. The expression of the IE gene was detected. Chromatin condensation and nuclear fragmentation along with dramatic changes of the mitochondria were observed by electron microscopy at 96 h post-infection. Cellular DNA fragmentation was observed in the infected cells, which had cells apoptotic rates of 4.1% and 45.7% at 96 h and 144 h post-infection, respectively.",
            "output": [
                "Does [ Human cytomegalovirus induce apoptosis of ECV304 endothelial-like cells ]?"
            ]
        },
        {
            "id": "task847-1c56d8e9672d431f98317864e545a598",
            "input": "In human breast cancers, amplification of chromosome 11q13 correlates with lymph node metastasis and increased mortality. To date, two genes located within this amplicon, CCND1 and EMS1, were considered to act as oncogenes, because overexpression of both proteins, respectively cyclin D1 and cortactin, correlated well with 11q13 amplification. Cyclin D1 is involved in cell cycle regulation and the F-actin-binding protein cortactin in cytoskeletal dynamics and cell migration. To study the role of cortactin in mammary gland tumorigenesis, we examined mouse mammary tumor virus (MMTV)-cortactin transgenic mice and MMTV-cortactin/-MMTV-cyclin D1 bitransgenic mice.', 'MMTV-cortactin transgenic mice were generated and intercrossed with previously described MMTV-cyclin D1 transgenic mice. Immunohistochemical, Northern and Western blot analyses were performed to study the expression of human transgene cortactin during mammary gland development and in mammary tumors. For tumor incidence studies, forced-bred, multiparous mice were used to enhance transgene expression in the mammary gland. Microscopical examination was performed using haematoxylin and eosin staining.', 'Mammary gland tumors arose stochastically (incidence 21%) with a mean age of onset at 100 weeks. This incidence, however, did not exceed that of aged-matched control FVB/N mice (38%), which unexpectedly, also developed spontaneous mammary gland tumors. We mimicked 11q13 amplification by generating MMTV-cortactin/-MMTV-cyclin D1 bitransgenic mice but did not observe any synergistic effect of cortactin on cyclin D1-induced mammary hyperplasias or carcinomas, nor development of distant metastasis.",
            "output": [
                "Do transgenic mice with mammary gland targeted expression of human cortactin develop ( pre-malignant ) breast tumors : studies in MMTV-cortactin and MMTV-cortactin/-cyclin D1 bitransgenic mice?"
            ]
        },
        {
            "id": "task847-92995d2b727c4be88257d86cd0c94154",
            "input": "Persistent infection with hepatitis C virus (HCV) leads to chronic hepatitis and hepatocellular carcinoma (HCC). RNA interference (RNAi) may act as a host antiviral response against viral RNA.', 'The effects of RNAi on both the replicative intermediates and the internal ribosome entry site (IRES) of HCV were studied by using HCV-related short interfering RNA (siRNA) detection assay. The mechanism that permits HCV to escape RNAi was studied by using RNAi assay materials.', 'These studies demonstrate that the Dicer, an RNase enzyme that generates short siRNA, can target and digest both the IRES and the replicative intermediate of HCV into siRNA of approximately 22 nucleotides. Further studies also show that Dicer can inhibit the replication of the HCV subgenomic replicon. However, the HCV core protein inhibits this RNAi and rescues the replication of the HCV subgenomic replicon through a direct interaction with Dicer.",
            "output": [
                "Is hepatitis C virus core protein a potent inhibitor of RNA silencing-based antiviral response?"
            ]
        },
        {
            "id": "task847-98f46db33068400186c99343fd837f1c",
            "input": "Pdx1 plays a pivotal role in pancreas organogenesis and specification of some types of cells in the duodenum and antral stomach. However, its expression is not restricted to pancreas, duodenum, and antral stomach but is also found in the common bile duct during embryogenesis. This study aimed to elucidate the role of Pdx1 in the development of the common bile duct, major duodenal papilla, and duodenum.', 'Expression pattern of pdx1 during embryogenesis and the morphology of the common bile duct, major duodenal papilla, and duodenum in pdx1 null mice were analyzed.', 'The major duodenal papilla, peribiliary glands, and mucin-producing cells in the common bile duct were not formed in pdx1 null mice. Pdx1 null mice had shorter periampullary duodenal villi than wild-type mice at postnatal stages associated with reduced cell proliferation and increased apoptosis of the duodenal epithelial cells. Loss of the major duodenal papilla allowed duodeno-biliary reflux and bile infection, resulting in the formation of brown pigment biliary stones in pdx1 null mice, and antibiotics treatment significantly reduced the incidence of biliary stone formation.",
            "output": [
                "Does loss of the major duodenal papilla result in brown pigment biliary stone formation in pdx1 null mice?"
            ]
        },
        {
            "id": "task847-31f2d8feb16b457eb98d9cfeb243fe04",
            "input": "Portal hypertension is associated with arterial hypotension and vascular hypocontractility, which persists despite elevated plasma levels of vasoconstrictors. We investigated the role of the RhoA/Rho-kinase pathway in vascular smooth muscle hypocontractility of rats with secondary biliary cirrhosis.', 'Aortic expressions of RhoA and Rho-kinase were analyzed in sham-operated and BDL rats by reverse-transcription polymerase chain reaction (RT-PCR) and immunoblots. Activation of aortic RhoA was examined by pull down of guanosine triphosphate (GTP)-RhoA and membrane translocation of RhoA. Rho-kinase activity was assessed as phosphorylation of its substrate, moesin. Contractility of isolated aortic rings was determined myographically. The hemodynamic effect of the Rho-kinase inhibitor (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632) was determined in vivo by measuring changes in mean arterial pressure and systemic vascular resistance (SVR) (microspheres).', 'Contraction of aortic rings from BDL rats was impaired in response to the alpha(1)-adrenergic receptor agonist methoxamine but not to high molar KCl. Aortic expression of RhoA was unchanged in cirrhotic rats, whereas Rho-kinase was down-regulated posttranscriptionally. Methoxamine-induced activation of RhoA as well as basal and methoxamine-induced phosphorylation of moesin were strongly reduced in aortas from cirrhotic rats. Aortic rings from cirrhotic rats precontracted with methoxamine showed an increased sensitivity to relaxation with Y-27632. The drop in SVR induced by Y-27632 was larger in cirrhotic rats than in sham-operated rats.",
            "output": [
                "Does defective RhoA/Rho-kinase signaling contribute to vascular hypocontractility and vasodilation in cirrhotic rats?"
            ]
        },
        {
            "id": "task847-1718ff48735043faa857dcd83e80faf3",
            "input": "Activation of trypsinogen to trypsin is a crucial step in the development of acute pancreatitis. The cause of this activation is not known although suggested explanations include autoactivation, cathepsin B-mediated activation and activation by mast cell tryptase. The aim of this study was to investigate cathepsin B and tryptase activation of pancreatic zymogens.', 'Trypsinogen-1, proelastase, and procarboxypeptidase B were purified from human pancreatic juice. Human cathepsin B and betaI-tryptase are commercial products. Activation and degradation of zymogens were measured by activity towards specific substrates for trypsin and pancreatic elastase, ELISAs for procarboxypeptidase B and its activation peptide, and a radioimmunoassay for the trypsinogen activation peptide.', 'Cathepsin B caused activation of trypsinogen-1 with a trypsin yield of about 30% of that produced by enterokinase. Proelastase and procarboxypeptidase B was not activated by cathepsin B. None of the zymogens were inactivated by cathepsin B. Neither monomeric nor tetrameric tryptase could activate any of the examined zymogens.",
            "output": [
                "Does cathepsin B activate human trypsinogen 1 but not proelastase 2 or procarboxypeptidase B?"
            ]
        },
        {
            "id": "task847-260ba0690ada4ac496fea22c3ecb17b1",
            "input": "Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A) on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats.', 'In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM) was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer.",
            "output": [
                "Does protein phosphatase 2A regulate central sensitization in the spinal cord of rats following intradermal injection of capsaicin?"
            ]
        },
        {
            "id": "task847-ac13e811ed2448b1894830d9643bb26a",
            "input": "Apoptosis occurring during ischaemia /reperfusion contributes independently to tissue damage, and involves activation of the stress-kinase, p38 MAPK during reperfusion. Ischaemic preconditioning (IPC) protects against ischaemia/reperfusion mediated necrosis and apoptosis. The role of p38 MAPK in the protective effect of preconditioning against apoptosis is unknown. Pharmacologic preconditioning with isoproterenol (beta-PC) also protects against necrosis, but it is not known whether it protects against apoptosis.', 'The aim of the study was to investigate whether the protective effect of IPC against apoptosis is related to activation of p38 MAPK and whether beta-PC also protects against apoptosis.', 'Isolated perfused rat hearts were used to study the effect of ischaemia and reperfusion on apoptosis and infarct size. Ischaemic preconditioning was elicited by 3 x 5 min global ischaemia, and beta-PC by 5 min isoproterenol 10(-7) M. For infarct size hearts were subjected to regional ischaemia for 35 min followed by 120 min reperfusion. Infarct size was determined by the tetrazolium staining technique, and expressed as percentage of area at risk. For markers of apoptosis hearts were subjected to global ischaemia of 25 min plus 30 min reperfusion. Apoptosis was determined by Western blot using antibodies against caspase-3 and PARP. p38 MAPK activation was inhibited by SB203580 (1 microM) administration 10 min prior to commencing ischaemia, and bracketing the IPC and beta-PC preconditioning protocols. p38 MAPK was activated by administration of anisomycin (5 microM) 10 min prior to index ischaemia in one protocol, and 10 min during reperfusion in non-preconditioned as well as IPC and beta-PC hearts. Results were analysed using ANOVA and a Newman-Keuls post-hoc test.', 'In the apoptosis model using global ischaemia, IPC and beta-PC both resulted in a significant decrease in p38 MAPK activation at the end of reperfusion when compared to non-preconditioned hearts. This was accompanied by a significant decrease in apoptosis as measured with both caspase-3 activation and PARP cleavage. Inhibiting p38 MAPK by administration of SB203580 10 min prior to ischaemia resulted in a significant reduction in both markers of apoptosis. Bracketing the triggering phase of either IPC or beta-PC with SB203580 resulted in attenuated p38 MAPK activation during reperfusion and did not abolish the protective effect of IPC or beta-PC against apoptosis. Activating p38 MAPK with anisomycin prior to ischaemia resulted in a reduction of markers of apoptosis, whereas activation of p38 MAPK with anisomycin during reperfusion did not exacerbate apoptosis in any groups, exept for an increase in PARP cleavage in IPC hearts. In the model of regional ischaemia, IPC and beta-PC reduced infarct size significantly, and to the same extent as inhibition of p38 MAPK by administration of SB203580 10 min prior to ischaemia. Bracketing the triggering phase of either IPC or beta-PC did not abolish the reduction in infarct size. Activating p38 MAPK during reperfusion was accompanied by an increase in infarct size only in IPC hearts, but not in beta-PC hearts.",
            "output": [
                "Is inhibition of myocardial apoptosis by ischaemic and beta-adrenergic preconditioning dependent on p38 MAPK?"
            ]
        },
        {
            "id": "task847-ca52356499484531922a1e10c51bb7e5",
            "input": "To investigate whether the Tiam1 gene expression enhances the invasive and metastatic capabilities of colorectal carcinoma cells.', 'Endogenous expression of Tiam1 in five colorectal carcinoma cell lines was investigated by RT-PCR. Tiam1/C1199HA cDNA was transfected into HT29, a colorectal carcinoma cell line without endogenous Tiam1 expression. RNA and protein expression of Tiam1 gene in the transfectants were detected by RT-PCR, immunohistochemistry and Western blot respectively. The biological behaviors of the transfectants were investigated by MTT and in-vitro invasion assays.', 'Tiam1 gene was highly expressed in LoVo and SW620 cells. Low level expression was seen in HCT116 and SW480 and no expression was found in HT29. Transfection of Tiam1 significantly increased the proliferation of HT29 cells along with markedly enhanced in-vitro invasion and metastasis.",
            "output": [
                "Does [ Tiam1 expression correlate with the biological behavior of human colorectal carcinoma cells ]?"
            ]
        },
        {
            "id": "task847-14debf527c024447b7a0fce05cc59df1",
            "input": "The assessment of microsatellite instability (MSI) is not included yet in the routine evaluation of patients with gastric cancer, as controversial data exist regarding its prognostic value.', 'We determined the clinical significance of MSI in 510 sporadic gastric cancers, using the mononucleotide markers BAT25 and BAT26. The results were compared with the immunohistochemical expression of the mismatch repair proteins Mlh1 and Msh2.', 'MSI was present in 83 (16%) cancers and correlated with better survival (P < .001). Multivariate analysis showed that the MSI phenotype was an independent factor (P = .005) and added prognostic information to TNM stage, location, and age. The relative risk of death for MSI cancer patients was 0.6 (95% confidence interval [CI], 0.4-0.8). Moreover, when grouped according to stage, only stage II cancers showed a significant effect of MSI status on survival (P = .011; hazard ratio = 0.3; 95% CI, 0.1-0.8). MSI also correlated with older age (P = .002), female gender (P < .001), intestinal histotype (P = .011), lower T stage (P = .018), and less lymph node involvement (P < .001). Finally, comparison of the results of immunohistochemical expression of the mismatch repair proteins Mlh1 and Msh2 with microsatellite analysis showed concordant results in 95% of neoplasms, with a sensitivity of 82% and specificity of 98%.",
            "output": [
                "Is microsatellite instability in gastric cancer associated with better prognosis in only stage II cancers?"
            ]
        },
        {
            "id": "task847-0be69e4d587847888cb1a3db8844907c",
            "input": "Nothing by mouth (NPO) is the standard treatment for small-bowel obstruction. Whether oral medications should be prohibited during treatment of adhesive, partial small-bowel obstruction is unclear. The goal of this study was to determine whether a combination of specific oral medications in adhesive, partial small-bowel obstruction will decrease the need for operative intervention.', 'Of 266 consecutive adult patients with partial small-bowel obstruction admitted at a tertiary medical center, 236 were randomized into 2 groups. Group I patients were treated with intravenous hydration, nasogastric tube decompression, and NPO. Group II patients were placed on intravenous hydration, nasogastric tube decompression, and oral fluids incorporating an oral laxative, a digestant, and a defoaming agent. We compared differences between the groups in (1) the number of patients having a successful nonoperative treatment, (2) complications, and (3) recurrence of symptoms.', 'A total of 116 and 120 patients comprised groups I and II, respectively. The number of patients treated successfully by a nonoperative approach was less in group I than in group II (77% vs 90%, P < .01). The complications and recurrence rate for groups I and II did not differ (4% vs 5% and 5% vs 4%, respectively).",
            "output": [
                "Do specific oral medications decrease the need for surgery in adhesive partial small-bowel obstruction?"
            ]
        },
        {
            "id": "task847-e86ae9925ed04af88ae6d56f96874e9a",
            "input": "The aim of this study was to compare the incidence of suicidal ideation and behaviors observed with antidepressant drug treatment to the incidence with placebo, in randomized, controlled pediatric clinical trials.', 'Manufacturers of nine antidepressant drugs identified suicidal adverse events in randomized, placebo-controlled, pediatric clinical trials that they had sponsored. Events were found with an electronic search for adverse event descriptions, including key words suggesting suicidal ideation or self-injury, along with a manual review of all adverse events meeting the standard regulatory definition for seriousness. Incidence rate data for these events supplied by the manufacturers were combined across trials to yield Mantel-Haenszel combined risk estimates.', 'Data from 22 randomized, short-term, placebo-controlled, pediatric trials in various indications, involving nine different antidepressant drugs, were available for analysis. A total of 2298 pediatric subjects were exposed to active drug, and 1952 to placebo. Seventy eight (78) serious suicidal adverse events occurred in these trials (54 with active drug and 24 with placebo); there were no completed suicides. The combined incidence rate ratio across all trials for serious suicidal adverse events was 1.89 (95% Confidence Interval, 1.18-3.04).",
            "output": [
                "Are suicidal adverse events in pediatric randomized , controlled clinical trials of antidepressant drugs associated with active drug treatment : a meta-analysis?"
            ]
        },
        {
            "id": "task847-67bb34e7e1a94a4e93664bc49acb5632",
            "input": "Non-alcoholic steatohepatitis (NASH) is a metabolic disorder of the liver, which may evolve to fibrosis or cirrhosis. Pentoxifylline (PTX) has been postulated to act as an antifibrogenic agent able to inhibit hepatic stellate cell proliferation and collagen synthesis in vitro. Short-term studies suggest beneficial effects of PTX in experimental models of NASH.', 'To study whether PTX can influence liver fibrogenesis in an animal model of NASH.', 'To induce NASH, a choline-deficient diet (CDD) was given to Sprague- Dawley rats for 8 weeks. Rats were allocated to two experimental groups one receiving PTX (9 mg/kg/day) in drinking water. Control rats received a choline-supplemented diet. Biochemical and histological evaluation of fatty liver was performed by conventional techniques. In addition, mRNA levels of Pro-collagen I and transforming growth factor beta-1 were assessed by semi-quantitative RT-PCR and stellate cell activation by alpha-actin immunofluorescence stain.', 'After 8 weeks CDD induced a marked elevation of serum aminotransferases, a marked decrease in both hepatic and biliary glutathione and a severe fatty liver infiltration with mild histological inflammation and fibrosis. A significant increase in mRNA levels of both Pro-collagen I and TGFbeta-1 was seen after CDD feeding. No differences were seen between rats receiving PTX and rats on CDD diet alone with regard to the biochemical, morphological or molecular alterations induced by the CDD.",
            "output": [
                "Does pentoxifylline prevent neither liver damage nor early profibrogenic events in a rat model of non-alcoholic steatohepatitis?"
            ]
        },
        {
            "id": "task847-df54b249410049d3809ba3baaa5e6944",
            "input": "To test the relationships among particular motives for smoking cessation, stage of readiness to quit (preparation or contemplation), and sociodemographic characteristics.', 'A cross-sectional study to examine attitudes toward and use of health promotion at the worksite, using a self-administered questionnaire.', 'Two German metal companies.', 'Of 1641 responding employees (response rate 65% in company A and 44% in company B), 360 smokers who intended to quit immediately (n = 105) or in the near future (n = 255) were analyzed.', \"The questionnaire comprised of sociodemographic characteristics, smoking behavior, smoking history, readiness to quit smoking, motives to quit, such as coworkers' complaints and health-related or financial concerns. Chi-squared tests and multiple logistic regression analyses were performed.\", \"Health-related reasons (94%) predominated financial (27%) or image-related (14%) reasons for smoking cessation. Participants in the cessation preparation group were more likely to report an awareness of being addicted (79.6% vs. 58.2%; p < .001) and the negative public image (22.5% vs. 11.6%; p < .01) as reasons for quitting compared with those in the contemplation group. In multivariable regression models, the motives for smoking cessation, including reduced performance, family's and coworkers' complaints, pregnancy/children, and negative public image, but not health-related and financial concerns, differed significantly by gender, age, marital status, education, and occupational status.",
            "output": [
                "Are motives for smoking cessation associated with stage of readiness to quit smoking and sociodemographics among German industrial employees?"
            ]
        },
        {
            "id": "task847-45c0feb425294178a08b0b3a46650bc3",
            "input": "Studies over many years have demonstrated that preoptimization and attention to appropriate perioperative care is associated with a substantial decrease in surgical mortality. This review discusses ways in which patient preparation and perioperative support can minimize surgical mortality and morbidity.', 'Scoring systems continue to be developed in order to classify categories of surgical risk. Objective physiologically based assessments can also identify high-risk groups of patients. Debate continues over the indications for specific interventions such as beta-blockade or statin therapy. There is continuing interest in perioperative optimization of oxygen delivery. A multimodality approach paying attention to a range of possible interventions appears to be beneficial. Audit, training, experience and a sufficient volume of procedures are all factors associated with surgical mortality.",
            "output": [
                "Does excellent anaesthesia need patient preparation and postoperative support to influence outcome?"
            ]
        },
        {
            "id": "task847-0e8e3cb789ab4f4ab2fdccce38b40902",
            "input": "Monitoring renal function is crucial in children undergoing chemotherapy. To date, a combination of routine serum creatinine (SCR) monitoring with occasional determination of creatinine clearance ratio (CCR) is widely used as clinical standard for this purpose. Both methods have their limitations regarding diagnostic value (SCR) or practicability (CCR), especially in young children. Diagnostic alternatives, such as glomerular filtration rate (GFR) estimation formulas have not been proved to be superior. The aim of the study was to evaluate whether serum cystatin C (CysC) may have a diagnostic impact on pediatric patients.', 'CysC, SCR, several GFR estimation formulas (Counahan-Barratt, Ghazali-Barratt, Schwartz, Shull, Traub), and CCR were studied in 80 pediatric cancer patients (age range: 0.17-17.9 years) during their chemotherapy. Special attention was given to children under the age of 3 in whom accurate urine collection for CCR is difficult.', 'All parameters correlated similarly well with CCR. Total accuracy was 66% and 67% for CysC and SCR, respectively. In very young children (<3 years), correlation with CCR was for CysC r = -0.74 with an area under the curve (AUC) of 0.646, and for SCR r = -0.27 with AUC = 0.594. Total accuracy was 60% for CysC, 50% for SCR.",
            "output": [
                "Is serum cystatin C a suitable marker for routine monitoring of renal function in pediatric cancer patients , especially of very young age?"
            ]
        },
        {
            "id": "task847-81079d1e9d564c868998a4aea187816b",
            "input": "The main pathology of haemodialysis graft stenosis is venous neointimal hyperplasia at graft-venous anastomoses. Neointimal hyperplasia is also observed in cases of coronary artery in-stent restenosis. Paclitaxel is a chemotherapeutic agent used to treat cancer, and has been proven to inhibit neointimal hyperplasia of coronary artery in-stent restenosis. In this study, we examined whether a paclitaxel-coated haemodialysis graft could inhibit neointimal hyperplasia and prevent stenosis.', 'We dip-coated paclitaxel on expanded polytetrafluoroethylene (ePTFE) grafts at a dose density of 0.59 microg/mm(2). In vitro release tests showed an initial paclitaxel burst followed by a long-term slow release. Using ePTFE grafts with (coated group, n = 8) or without a paclitaxel coating (control group, n = 11), we constructed arteriovenous (AV) grafts connecting the common carotid artery and the external jugular vein in Landrace pigs.', 'After excluding seven pigs for technical failure, cross-sections of graft-venous anastomoses obtained 6 weeks after placing the AV grafts were analysed. Percentage luminal stenosis, ratios of intima to media in whole cross-sections, areas of intima in the peri-junctional areas (within 2 mm above and 2 mm below the graft-venous junction), and the mean thickness of intima within venous sides of cross-sections, were 60.5% (range, 41.5-60.7), 13.0 (range, 8.6-20.4), 23.7 mm(2) (range, 10.8-32.1) and 2.1 mm (range, 1.1-3.0), respectively, in the control group, whereas corresponding median values in the coated group were 10.4% (range, 1.0-17.8), 1.0 (range, 0.7-5.1), 1.6 mm(2) (range, 0.2-8.0) and 0.3 mm (range, 0.1-2.2). All parameters were significantly different between the two groups (P<0.05 by Mann-Whitney test).",
            "output": [
                "Do paclitaxel-coated expanded polytetrafluoroethylene haemodialysis grafts inhibit neointimal hyperplasia in porcine model of graft stenosis?"
            ]
        },
        {
            "id": "task847-69e07a057d9545308cb3a55421915a8e",
            "input": "To investigate the effect of arg-gly-asp-mannose-6 phosphate (RGD-M6P) on the activation and proliferation of primary hepatic stellate cells in vitro.', 'Hepatic stellate cells (HSCs) were isolated from rats by in situ collagenase perfusion of liver and 18% Nycodenz gradient centrifugation and cultured on uncoated plastic plates for 24 h with DMEM containing 10% fetal bovine serum (FBS/DMEM) before the culture medium was substituted with 2% FBS/DMEM for another 24 h. Then, HSCs were cultured in 2% FBS/DMEM with transforming growth factor beta1, M6P, RGD, or RGD-M6P, respectively. Cell morphology was observed under inverted microscope, smooth muscle alpha-actin (alpha-SMA) was detected by immunocytochemistry, type III procollagen (PC III) in supernatant was determined by radioimmunoassay, and the proliferation rate of HSCs was assessed by flow cytometry.', 'RGD-M6P significantly inhibited the morphological transformation and the alpha-SMA and PC III expressions of HSCs in vitro and also dramatically prevented the proliferation of HSCs in vitro. Such effects were remarkably different from those of RGD or M6P.",
            "output": [
                "Does arg-gly-asp-mannose-6-phosphate inhibit activation and proliferation of hepatic stellate cells in vitro?"
            ]
        },
        {
            "id": "task847-b9198c4fbdb046088483b0af39e636a9",
            "input": "Circulating adiponectins have multiple protective roles as anti-diabetic, anti-atherosclerotic, and anti-inflammatory factors. We examined the relationship between plasma adiponectin concentration and other cardiovascular risk in nondiabetic coronary artery disease (CAD) men and the relationship can be maintained even after adjusted for major environmental factors that contribute to adiponectin concentrations.', 'Nondiabetic CAD men (n=613) were 31-70 y and had body mass index (BMI) of 18.5-29.9 kg/m2.', \"Circulating adiponectins positively correlated with age and negatively with BMI, waist circumference and % body fat (p-values of all <0.001). Plasma adiponectin concentrations were higher in never-smokers (5.07+/-0.30 microg/ml) than current (4.15+/-0.12 microg/ml) and ex-smokers (3.75+/-0.20 microg/ml) both before and after adjusted for age and adiposity (p=0.002 and p=0.008, respectively), however they were not significantly different according to alcohol drinking status. After adjusted for age, adiposity and cigarette smoking, plasma adiponectin still have positive correlations with HDL cholesterol, apolipoprotein AI and LDL particle size, and inversely with fasting triglyceride, atherogenic index, insulin resistance and C-reactive protein (CRP). However there was no significant relationships between adiponectin and apolipoprotein B, total cholesterol or LDL cholesterol. In subset analysis by tertile adiponectin concentrations (lowest: <2.92, moderate: 2.92<or=adiponectin<4.75, highest: >or=4.75 microg/ml), 'moderate' and 'highest' adiponectin groups had lower triglyceride (p<0.001), lower atherogenic index (p=0.001), lower fasting insulin (p=0.004), lower insulin resistance (p=0.001), lower CRP (p=0.001), higher HDL cholesterol (p<0.001), higher apolipoprotein AI (p=0.005) and higher LDL particle size (p<0.001) as compared with 'lowest' adiponectin group when adjusted for age, adiposity and cigarette smoking. Platelets were lower in 'highest' adiponectin groups as compared with 'lowest' and 'moderate' adiponectin group after the adjustment. However, there was no significant difference in total cholesterol (p=0.145), LDL cholesterol (p=0.145), apolipoprotein B (p=0.222) and fasting glucose (p=0.157).",
            "output": [
                "Is plasma adiponectin related to other cardiovascular risk factors in nondiabetic Korean men with CAD , independent of adiposity and cigarette smoking : cross-sectional analysis?"
            ]
        },
        {
            "id": "task847-b90bbcfcec404a91af5c0fe39c3e1418",
            "input": "To determine the frequency of pulmonary embolism (PE) diagnosis when different alternative diagnoses were considered most likely before testing, because the relationship between specific alternative diagnoses and the diagnosis of PE has not been explored.', \"This study was a preplanned secondary analysis of a prospective study of the diagnosis of pulmonary embolism conducted in the emergency department (ED) of an urban university hospital. Physicians were queried as to their most likely pretest diagnosis when they ordered any of the following tests to evaluate possible PE: D-dimer, contrast-enhanced computed tomography of the chest, ventilation-perfusion lung scan, or pulmonary angiogram. To compare the frequency of PE diagnosis across alternative diagnoses, risk ratios, 95% confidence intervals (CI), and p-values using Fisher's exact test were calculated.\", 'Six hundred seven patients were enrolled, and 61 had PE. Physicians thought PE was the most likely pretest diagnosis in 162 (26.7%) patients, and 20.4% (95% CI = 14.4% to 27.4%) of these patients had PE. For four alternative diagnoses, PE was diagnosed less frequently than when PE was considered most likely: musculoskeletal pain (2.2%, 95% CI = 0.4% to 6.2%), anxiety (1.7%, 95% CI = 0.0 to 9.2%), asthma or chronic obstructive pulmonary disease (0, 95% CI = 0.0 to 10.9%), and viral syndrome (0, 95% CI = 0.0 to 14.3%).",
            "output": [
                "Is the probability of pulmonary embolism a function of the diagnoses considered most likely before testing?"
            ]
        },
        {
            "id": "task847-d605f486c8994a0d95fce945276dbcfd",
            "input": "In children there is frequently a reason to exclude cystic fibrosis. Sweat testing is used for this. Because sweat testing has some disadvantages we investigated whether analyzing DNA for the local most common CFTR mutations, harvested from buccal cells, is reliable as a method to exclude cystic fibrosis.', 'In patients in whom a sweat test had been ordered during the period January 1, 2002 to December 31, 2004, we harvested buccal cell DNA for analysis. When blood was available, DNA from leukocytes was also analyzed.', 'A total of 73 sweat tests were ordered during the two-year study period, mostly because of recurrent pulmonary infections (36; 49%), failure to thrive (20; 27%) and chronic diarrhea (10, 14%). In 70, children the results of the sweat test were normal, in three patients the results were borderline. Sixty buccal smears were analyzed and no patient was homozygous for cystic fibrosis, two were heterozygous for cystic fibrosis. In none of the children the diagnosis of cystic fibrosis was established.",
            "output": [
                "Is analyzing DNA from buccal cells a reliable method for the exclusion of cystic fibrosis . Results of a pilot study?"
            ]
        },
        {
            "id": "task847-ecc2e4176a95445caa68c632c99873f4",
            "input": "Polymorphisms in cytokine genes can determine their level of expression and affect the phenotypic expression of immunomediated diseases, such as celiac disease (CD). We thus evaluated cytokine polymorphism prevalence in CD patients and population controls, and assessed the correlation between specific polymorphisms and celiacs' clinical characteristics.\", \"155 CD patients and 202 population controls were enrolled in the study. Cytokine polymorphisms (TNFalpha -308 and -238, IL-1beta -511 and +3954, IL-1b RN + 2018, IL-6 -174, IL-10 -1082, -819 and -592, TGFbeta1 + 29 and +74, IFN-gamma + 874) and HLA class II alleles were determined by sequence-specific primer polymerase chain reaction or restriction fragment length polymorphism analysis. Duodenal histology was classified using Marsh's criteria. Variables significantly associated with CD patients' characteristics were identified by multivariate logistic regression analysis.\", 'A significantly higher frequency of -308 TNFalpha polymorphism was observed in CD patients compared to the entire population control group, although no difference was detected when population controls were stratified according to HLA class II. Among celiacs, early onset of the disease (< or =2 year old) and the presence of a severe intestinal lesion (Marsh 3C) were significantly associated with the -1082 A/A IL-10 genotype which corresponds to a low producer phenotype (OR 3.28, 95% CI 1.49-7.19 and OR 2.60, 95% CI 1.04-6.49, respectively).",
            "output": [
                "Are iL-10 polymorphisms associated with early-onset celiac disease and severe mucosal damage in patients of Caucasian origin?"
            ]
        },
        {
            "id": "task847-fbef3420e91a40f5a515d8c3268212aa",
            "input": "Mycobacterium avium is capable of invading the intestinal epithelial cells, which requires cytoskeleton rearrangement and protein phosphorylation in the host cell. However, little is known about the mechanism.', 'A transposon bank was screened for invasion-impaired mutants.', 'Among the genes identified, inactivation of the fadD2 gene resulted in approximately 50% reduction in invasion in vitro and 100-fold reduction in invasion in vivo, compared with the wild-type (wt) strain. Invasion by wt M. avium led to the recruitment of neuronal Wiskott-Aldrich syndrome protein (N-WASp), which was not observed with mutant lacking a functional fadD2 gene. M. avium entry resulted in the phosphorylation of N-WASp and activation of the Arp2/3 complex. Supernatant obtained from wt M. avium incubated with HEp2 epithelial cells rescued the mutant 1B2 ability to enter the cells, which suggests that activation of Cdc42 probably follows the secretion of M. avium proteins.",
            "output": [
                "Is the fadD2 gene required for efficient Mycobacterium avium invasion of mucosal epithelial cells?"
            ]
        },
        {
            "id": "task847-2828e4e21da243fbb59fafa05e337f78",
            "input": "To examine antigen (Ag)-specific CTL response during anterior chamber associated immune deviation (ACAID).', \"OVA or OVA257-264 peptide was injected into the anterior chamber (AC) of C57BL/6 mice. There were 16 mice in each ACAID group induced with OVA or OVA257-264 peptide. The mice were primed by SC injection with OVA or OVA 257-264 peptide in complete Freund's adjuvant (CFA) on day 7. Ag-specific CD8+ T cells in spleens were analyzed on day 14 using Pentamer H-2K(b)-SIINFEKL(OVA257-264 peptide). IFN-gamma ELISPOT and intracellular granzyme B staining were used to characterize the CTL response. Twelve mice in each group immunized with OVA or OVA257-264 peptide in CFA served as positive controls. Twelve normal mice served as negative controls and 12 receiving injection of CFA as CFA controls for studying the influence of CFA on the Ag-specific CTL response.\", 'The results showed that anterior chamber inoculation of OVA or OVA257-264 peptide could induce ACAID as evidenced by an impaired DTH response. The frequency of Ag-specific CD8+ T cells in ACAID mice was not different from that in mice challenged with Ags in CFA only (positive controls). IFN-gamma production by these cells in ACAID mice was not different compared to positive controls. However, Ag-specific CD8+ T cells in ACAID mice failed to secrete granzyme B. Mice challenged only with OVA peptide and CFA also showed a granzyme B negative CD8+ T cell response. Ag-specific CTL response induced by CFA alone was similar with the negative control.",
            "output": [
                "Do oVA-specific CD8+ T cells do not express granzyme B during anterior chamber associated immune deviation?"
            ]
        },
        {
            "id": "task847-d09c03bea9ca435d929e70e5eb2d701a",
            "input": "The aim of the study was to compare the diameter response of retinal arterioles and retinal thickness in patients with different stages of diabetic maculopathy during an increase in the arterial blood pressure.', 'Four groups each consisting of 19 individuals were studied. Group A consisted of normal individuals and groups B-D consisted of type 2 diabetic patients matched for diabetes duration, age, and gender, and characterized by: Group B no retinopathy, Group C mild retinopathy, Group D maculopathy not requiring laser treatment. The diameter changes of a large retinal arteriole were measured using the Retinal Vessel Analyzer (RVA, Imedos, Germany) before, during, and after an increase in the blood pressure induced by isometric exercise. Additionally, the retinal thickness was measured using optical coherence tomography scanning.', 'The arterioles contracted during isometric exercise in normal persons (diameter response: -0.70+/-0.48%) and in patients with no retinopathy (-1.15+/-0.44%), but dilated in patients with mild retinopathy (0.41+/-0.49%) and diabetic maculopathy (0.54+/-0.44%), p=0.01. Retinal thickness was normal in Group A (260+/-5.0 microm), Group B (257+/-4.5 microm), and Group C (253+/-4.4 microm), but was significantly (p=0.006) increased in Group D (279+/-5.3 microm).",
            "output": [
                "Does the blood pressure-induced diameter response of retinal arterioles decrease with increasing diabetic maculopathy?"
            ]
        },
        {
            "id": "task847-11f54fb877db43809368d7fdca6b4aae",
            "input": "To assess the therapeutic effects of flexible magnets on pain perception, intramuscular swelling, range of motion, and muscular strength in individuals with a muscle microinjury.', 'This experiment was a single-blind, placebo study using a repeated-measures design. Subjects performed an intense exercise protocol to induce a muscle microinjury. After pretreatment measurements were recorded, subjects were randomly assigned to an experimental (magnet), placebo (imitation magnet), or control (no magnet) group. Posttreatment measurements were repeated at 24, 48, and 72 hours.', 'Forty-five healthy subjects participated in the study.', 'Subjects were measured repeatedly for pain perception, upper arm girth, range of motion, and static force production. Four separate univariate analyses of variances were used to reveal statistically significant mean (+/-SD) differences between variables over time. Interaction effects were analyzed using Scheffe post hoc analysis.', 'Analysis of variance revealed no statistically significant (P > .05) mean differences between conditions for any dependent pretreatment and posttreatment measurements. No significant interaction effects were demonstrated between conditions and times.",
            "output": [
                "Are flexible magnets effective in decreasing pain perception and recovery time after muscle microinjury?"
            ]
        },
        {
            "id": "task847-a41bfd1117e64234995293699f94c64d",
            "input": "Ischemia reperfusion (I/R)-associated early graft pancreatitis is a major complication after pancreas transplantation. The influence of immunosuppressants on graft pancreatitis remains unclear. The aim of this study was to evaluate ciclosporin and tacrolimus in experimental pancreatic I/R.', 'Moderate pancreatitis was induced in rats by I/R injury. Animals were assigned to 4 groups: (1) control without I/R, (2) I/R without therapy, (3) I/R + ciclosporin, or (4) I/R + tacrolimus. After 24 hours, pancreatic damage was evaluated by amylase, endothelin 1, thromboxane A2, and histology. Additionally, microcirculation was evaluated 12 hours after reperfusion by intravital microscopy.', 'I/R significantly increased amylase compared with controls, with maximum levels after ciclosporin treatment. Histology showed comparable tissue injury in control and tacrolimus-treated animals. Ciclosporin-treated animals developed significantly (P < 0.05) more inflammation and necrosis compared with the other groups. Erythrocyte velocity evaluated by intravital microscopy was reduced in all animals after I/R. This was significantly pronounced after ciclosporin application. There was a significant increase of adherent leukocytes and platelets in ciclosporin-treated animals compared with both other groups.",
            "output": [
                "Does ciclosporin aggravate tissue damage in ischemia reperfusion-induced acute pancreatitis?"
            ]
        },
        {
            "id": "task847-a3b83706f3544e89a0ff1a81f4c191ac",
            "input": "Chronotropic incompetence, an attenuated heart rate (HR) response to exercise, is an independent predictor of cardiovascular mortality, but it is not known whether chronotropic incompetence is related to carotid atherosclerosis. The association between chronotropic incompetence and carotid atherosclerosis in 8567 (age 47.6+/-8.8 years) healthy men was examined.', 'Chronotropic incompetence was defined as the failure to achieve 85% of the age-predicted maximal HR (APMHR), <80% HR reserve (HRR), and chronotropic response index (CRI). Carotid atherosclerosis was defined, using B-mode ultrasonography, as stenosis >25% and/or intima-media thickness (IMT) of >1.2 mm. In multivariable adjusted logistic regression models, the subjects who achieved less than 85% of APMHR exhibited an odds ratio (OR) of 1.72 [95% confidence intervals (CI): 1.32-2.22] for carotid atherosclerosis. Subjects with <80% of HRR were 1.45 (95% CI: 1.14-1.84) times more likely to have carotid atherosclerosis after multivariate adjustment. Also, the OR of carotid atherosclerosis across quartiles of CRI (highest to lowest) was 1.51 (95% CI: 1.10-2.09) after multivariate adjustment.",
            "output": [
                "Is chronotropic response to exercise testing associated with carotid atherosclerosis in healthy middle-aged men?"
            ]
        },
        {
            "id": "task847-555dcde430ec4794a44c8962edba38b1",
            "input": "To evaluate newly diagnosed non-arteritic anterior ischaemic optic neuropathy (NAION) patients for the existence of an associated sleep apnoea syndrome.', 'Newly identified NAION patient underwent polysomnography. The prevalence of sleep apnoea in NAION patients was compared to the prevalence previously found in the general population. Hypertension, diabetes, hyperlipidaemia, and atheromatous lesions of carotid vessels as classic risk factors associated with NAION were also identified.', '27 consecutive newly diagnosed NAION patients (18 men and nine women, mean age 65 (SD 8) years, body mass index 27.2 (3.8) kg/m2) were included in the study. 24 of these 27 NAION patients (89%) exhibited a sleep apnoea syndrome (respiratory disturbance index: 37.2/h (SD 18.3/h). Risk ratio for a NAION patient to have sleep apnoea was 4.9 compared to the general population (p < 0.001). Sleep apnoea was 1.5-2-fold more frequent than the rate of the other identified risk factors typically associated with NAION (hypertension, diabetes).",
            "output": [
                "Is non-arteritic anterior ischaemic optic neuropathy nearly systematically associated with obstructive sleep apnoea?"
            ]
        },
        {
            "id": "task847-fcc56ebc538048388d84f46e341fe036",
            "input": "Irritable bowel syndrome is a frequently diagnosed gastrointestinal condition in general practice. Managing this chronic condition requires a co-ordinated effort between patient and doctor.', 'To explore the patterns of treatment and healthcare utilization of irritable bowel syndrome cases in a Swedish primary care setting.', 'All cases with a registered diagnosis of irritable bowel syndrome were identified retrospectively for a 5-year period through computerized medical records at three primary healthcare centres in Sweden. Documentation of diagnosis, healthcare visits, treatments, investigations, medications, referrals, laboratory tests, mental and demographic data were retrieved from the records.', 'Of all 723 irritable bowel syndrome patients identified, only 37% had a follow-up appointment to their General Practitioner during the study period. For 80%, the General Practitioner initiated some treatment during the initial consultation and 75% were prescribed medication. Fibre and bulking laxatives and acid-suppressive drugs were the most common medication. Almost a quarter was referred for complementary investigations at hospital, only 8.9% of the irritable bowel syndrome patients were referred to a specialist investigation. Laboratory investigations varied and were ordered more frequently (P = 0.05) for men.",
            "output": [
                "Appear patients with irritable bowel syndrome in primary care to be heavy healthcare utilizers?"
            ]
        },
        {
            "id": "task847-afa76663337848e0a5c74f0580eab997",
            "input": "One of the major reasons for failure of radiotherapeutic cancer treatment is the limitation in dose that can be applied to the tumor because of coirradiation of the normal healthy tissue. Late radiation-induced damage reduces the quality of life of the patient and may even be life threatening. Replacement of the radiation-sterilized stem cells with unirradiated autologous stem cells may restore the tissue function. Here, we assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived cells (BMC) to regenerate and functionally restore irradiated salivary glands used as a model for normal tissue damage.', 'Male-eGFP+ bone marrow chimeric female C57BL/6 mice were treated with G-CSF, 10 to 60 days after local salivary gland irradiation. Four months after irradiation, salivary gland morphology and flow rate were assessed.', 'G-CSF treatment induced homing of large number of labeled BMCs to the submandibular glands after irradiation. These animals showed significant increased gland weight, number of acinar cells, and salivary flow rates. Donor cells expressed surface markers specific for hematopoietic or endothelial/mesenchymal cells. However, salivary gland acinar cells neither express the G-CSF receptor nor contained the GFP/Y chromosome donor cell label.",
            "output": [
                "Does mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorate radiation-induced damage to salivary glands?"
            ]
        },
        {
            "id": "task847-f7ac228eac7f4505b598816b43b08817",
            "input": "Different antiangiogenic approaches have been proposed in cancer treatment where therapeutic efficacy has been shown with the addition of cytotoxic agents. Here, we used SU6668, a small-molecule receptor tyrosine kinase inhibitor, to investigate the combinatorial effect with paclitaxel on the cellular populations of the developing vasculature.', 'The effect of this combination was evaluated in vitro in a 72-hour proliferation assay on human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells derived from lungs, endothelial cells, aortic smooth muscle cells, and human ovarian carcinoma cells sensitive (1A9) and resistant (1A9-PTX22) to paclitaxel. Combination data were assessed by isobologram analysis. Cell survival was determined by terminal deoxyribonucleotide transferase-mediated nick-end labeling and Annexin V staining. The activity of the combination in vivo was evaluated in fibroblast growth factor-2-induced angiogenesis in Matrigel plugs s.c. implanted in mice. The 1A9-PTX22, paclitaxel-resistant xenograft model was used to evaluate tumor response.', 'Combination index values and isobologram analysis showed synergy in inhibition of proliferation of HUVEC, human microvascular endothelial cells derived from lungs, and aortic smooth muscle cells. The combination induced greater apoptosis in HUVEC than the single agents. The addition of paclitaxel to the treatment with SU6668 significantly decreased the hemoglobin content and the number of CD31-positive vessels in Matrigel plugs in vivo. The combination of the drugs was more active than either single agent against 1A9-PTX22 xenografts; the tumor growth delay was accompanied by a significant reduction of vascular density.",
            "output": [
                "Is the vascular targeting property of paclitaxel enhanced by SU6668 , a receptor tyrosine kinase inhibitor , causing apoptosis of endothelial cells and inhibition of angiogenesis?"
            ]
        },
        {
            "id": "task847-aadb5f0a701f461f9373527b4fca01e5",
            "input": "Leucocytes have been implicated as mediators of renal ischaemia-reperfusion injury. This study aimed to demonstrate the effect of white cells in early renal reperfusion injury using an isolated haemoperfused porcine kidney model.', 'After 2 h cold storage, porcine kidneys were perfused with normothermic autologous blood using an isolated organ preservation system. This was designed using cardiopulmonary bypass technology, and perfusion commenced with a circulating serum creatinine level of 1000 micromol/l. In group 1 (n = 6) a leucocyte filter was included in the circuit and in group 2 (n = 6) non-filtered blood was used.', 'The mean(s.d.) area under the curve for serum creatinine was lower in the leucocyte-depleted experiments (1286(214) versus 2627(418); P = 0.002). Leucocyte depletion also led to improved urine output (191(75) versus 70(32) ml/h; P = 0.002) and higher creatinine clearance (10.6(2.8) versus 1.9(1.0) ml/min; P = 0.002). Renal blood flow, oxygen consumption and acid-base homeostasis were all improved by perfusion with leucocyte-depleted blood, and histological tubular damage was ameliorated.",
            "output": [
                "Does leucocyte depletion improve renal function during reperfusion using an experimental isolated haemoperfused organ preservation system?"
            ]
        },
        {
            "id": "task847-a88b6869e73e4e318954ff8a3b692bf8",
            "input": "The aim was to assess the effect of population-based mammography screening on treatment costs for fatal breast cancer in Turku, Finland.', 'The study included 556 women with invasive breast cancer, diagnosed at the age of 40-74 years in 1987-1993: 427 in the screened group (screen-detected or interval cancer) and 129 in the unscreened group (not yet invited or refused screening). Both groups were followed up for 8 years from diagnosis.', 'In the unscreened group, 32 (25%) patients died of breast cancer versus 49 (12%) in the screened group (p < 0.001). The non-discounted mean treatment costs were 2.8-fold for those dying of breast cancer compared to survivors: 26,222 euros versus 9,434 euros; the difference between means was 16,788 euros (95% CI 14,915-18,660) (p<0.001). The mean costs for fatal cases were high, irrespective of the way cancer was detected: 23,800 euros in the unscreened group versus 27,803 euros in the screened group; the difference between means was -4,003 euros (-10,810 to 2802) (p=0.245). In the unscreened group, patients with fatal breast cancer accounted for 41% (0.76/1.87 million euros) of the total treatment costs versus 29% (1.36/4.76 million euros) in the screened group. It was estimated that about one third of costs for fatal breast cancer were avoided through mammography screening, accounting for 72-81% of the estimated total treatment cost savings achieved by screening. About 31-35% of the screening costs for 1987 to 1993 were offset by savings in treatment costs.",
            "output": [
                "Does population-based mammography screening result in substantial savings in treatment costs for fatal breast cancer?"
            ]
        },
        {
            "id": "task847-4d12f343f1b4435aa1de1d303c7fa8e2",
            "input": "To determine whether deguelin can regulate the expression of nuclear factor kappa B (NF-kappaB) binding protein (IkappaBalpha) in U937 human leukemia cells and Raji human B lymphoma cells.', 'The localization of IkappaBalpha protein was investigated by using an immunofluorescence method. The expression of IkappaBalpha and NF-kappaB /p65 proteins in Raji and U937 cells were investigated by using Western blotting. Apoptosis was detected through annexin V/PI double-labeled cytometry.', 'IkappaBalpha localized in the cytoplasm in untreated and deguelin-treated cells. After treatment with tumor necrosis factor alpha (TNF-alpha) or deguelin plus TNF-alpha for 15 min, there was a substantial reduction in the amount of IkappaBalpha protein. The expression of IkappaBalpha was downregulated by deguelin in Raji and U937 cells. Deguelin induced apoptosis in U937 cells.",
            "output": [
                "Does deguelin inhibit expression of IkappaBalpha protein in Raji and U937 cells?"
            ]
        },
        {
            "id": "task847-1375d381826c432cbc8dd995e4560e55",
            "input": "The present study aims at investigating the involvement of several genes in the cell cycle distribution and apoptosis in U937 cells, a cell line lacking functional p53 protein, after combined treatment with staurosporine and irradiation.', 'Using a DNA fragmentation assay, flow cytometry and western blot analysis, the molecular basis for the effects of staurosporine in combination with the irradiation of leukemia cells was investigated.', 'Our results indicated that combined treatment led to an increased apoptotic cell death in U937 cells, which is correlated with the phosphorylation of the V-Jun sarcoma virus 17 oncogene homolog (c-JUN) NH(2)-terminal kinase protein (JNK), the activation of caspases, the increase in B cell leukemia/lymphoma 2 (Bcl-2) associated X protein (Bax), the decrease in Bcl xL protein (Bcl-XL) levels, the loss of mitochondria membrane potential and the release of cytochrome c.",
            "output": [
                "Does staurosporine modulate radiosensitivity and radiation-induced apoptosis in U937 cells?"
            ]
        },
        {
            "id": "task847-c2c6053a1b88409ba154756c1741bad8",
            "input": "Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a Th2 immune response. Mouse models suggest a critical role for the Th2 chemokines thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in ABPA.', 'To determine whether serum levels of TARC and MDC characterize ABPA in patients with cystic fibrosis (CF) and to examine longitudinally if levels of TARC and MDC indicate ABPA exacerbations in patients with CF.', 'Levels of TARC and MDC and levels of Th1 (IL-12 and IFN-gamma) and Th2 (IL-4, IL-5, and IL-13) cytokines were analyzed in serum of 16 patients with CF with ABPA, six non-CF patients with asthma with ABPA, 13 patients with CF colonized with Aspergillus fumigatus, six patients with CF sensitized to A. fumigatus, 12 atopic patients with CF, and 13 non-CF atopic control subjects by ELISA. The longitudinal course of TARC, MDC, and IgE levels was assessed during ABPA episodes.', 'Patients with ABPA had significantly higher serum levels of TARC compared with the other patient groups. Cytokine levels did not differ among the patient groups. Longitudinally, levels of TARC indicated ABPA exacerbations in patients with CF more clearly than IgE levels. In patients with CF and ABPA, levels of TARC correlated positively with specific IgE to A. fumigatus and rAsp f4.",
            "output": [
                "Do chemokines indicate allergic bronchopulmonary aspergillosis in patients with cystic fibrosis?"
            ]
        },
        {
            "id": "task847-1b476b7e2ad34d539356f25fc32b1c7d",
            "input": "To study the outcome of EEG from patients with Chiari I malformations and nonspecific EEG abnormalities, after posterior fossa decompression and CSF flow normalization.', \"Three 'apparently asymptomatic' children who had been diagnosed with Arnold-Chiari type 1 EEG abnormalities and who exhibited (a) a wide range of abnormalities according to common anatomical Chiari MRI classifications (Elster AD, Chen MY. Chiari I malformations: clinical and radiologic reappraisal. Radiology 1992;183:347-53), (b) a lack of specific, clinical signs of increased intracranial pressure, and (c) apparently unrelated, EEG-nonspecific abnormalities (focal intermittent rhythmic delta activity (IRDA)--solely in patients 1 and 3, and with focal IRDA plus spikes and spike waves of high voltage in patient 2). Standard EEGs were recorded before surgery and within one month of surgery, which was performed in conjunction with intraoperative echo-Doppler ultrasonography to control CSF flow. Subsequent EEGs and clinical follow-ups were performed within 6-12 months of surgery.\", 'In all patients, intraoperative echo-Doppler ultrasonographic control demonstrated poor CSF flow, which was completely restored by posterior fossa decompression. In all patients, the EEG abnormalities disappeared within one month of surgery and the EEGs were normal at follow-up.",
            "output": [
                "Does surgery remove EEG abnormalities in patients with Chiari type I malformation and poor CSF flow?"
            ]
        },
        {
            "id": "task847-5205c7f1c17b43a2adae674c0bff6820",
            "input": "Tinnitus can adversely affect patients' quality of life. Transcutaneous electrical nerve stimulation (TENS) may be effective in the management of tinnitus. No study has investigated the efficacy of TENS for the management of tinnitus by means of quality of life measures. In this study, we evaluated the efficacy of TENS for the management of tinnitus symptoms by using the visual analogue scale (VAS), tinnitus handicap inventory test, Nottingham health profile (NHP) and short form-36 (SF-36) questionnaires.\", 'Twenty-two patients were included in this study (male/female, 16/6; mean age, 48.04 +/- 15.57 years). Nine patients had unilateral and 13 patients had bilateral tinnitus.', 'After TENS, improvement measured by VAS was only marginally significant (p = 0.059). However, after TENS, there were statistically significant improvements regarding tinnitus severity scores, tinnitus handicap inventory scores, NHP fatigue, social isolation and emotional problems scores, and many parameters measured by the SF-36 (physical functioning, general health, vitality, social functioning, role limitations due to emotional problems, and mental health)(p < 0.05).",
            "output": [
                "Does treatment of tinnitus with transcutaneous electrical nerve stimulation improve patients ' quality of life?"
            ]
        },
        {
            "id": "task847-d7d6de71bd9846358f52e12595816458",
            "input": "To analyze the effect of antiretroviral therapy, including drugs that have good penetration in cerebrospinal fluid (CSF), on neuropsychologic performance.', 'One hundred sixty-five HIV-1-infected patients exposed to a stable highly active antiretroviral therapy (HAART) regimen were studied. Neuropsychologic examinations were performed for all patients.', \"A total of 50.3% of patients were impaired. In multivariate analysis, older age (for 10-year increase, odds ratio [OR] = 4.8, 95% confidence interval [CI]: 2.2 to 10.4; P< 0.0001) and higher plasma HIV-1 RNA levels (OR = 1.90, 95% CI: 1.1 to 3.2; P = 0.021) at testing were independently associated with an increased probability of impaired neurocognitive performance, whereas higher educational level was a protective factor (OR = 0.76, 95% CI: 0.65 to 0.90; P=0.001). A significant linear correlation was observed between the neuropsychologic z score for 8 tests (NPZ8) score, a quantitative parameter of neurocognitive impairment, and CD4 cell count at neuropsychologic testing (R = 0.273, P = 0.001) and between the NPZ8 score and the patient's age (R = 0.288, P = 0.001).",
            "output": [
                "Do neuroactive antiretroviral drugs influence neurocognitive performance in less advanced HIV-infected patients responding to highly active antiretroviral therapy?"
            ]
        },
        {
            "id": "task847-c74f3033842c426381b0db14e4820146",
            "input": "The conversion of cortisol (F) to cortisone (E) is catalyzed by 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). Children suffering from chronic renal failure (CRF) have a decreased activity of 11beta-HSD2 contributing to increased arterial blood pressure. The objective was to investigate whether a normal conversion of F to E is achieved after renal transplantation (TX) in children.', 'Fifteen children with CRF, 17 children with steroid-free immunosuppression after TX, and 18 healthy controls (CO) were enrolled. The activity of 11beta-HSD2 in plasma was calculated using the ratio of F/E determined by tandem mass spectrometry, the ratio of tetrahydrocortisol (THF) +5alpha-tetrahydrocortisol (5alphaTHF) in urine determined by gas chromatography/mass spectrometry, and the ratio of (THF +5alphaTHF)/tetrahydrocortisone (THE) in urine determined by tandem mass spectrometry.', 'The F/E ratio (mean +/- S.D./S.E.M.) was significantly higher in CRF and TX (5.6 +/- 1.9/0.6, 7.12 +/- 3.1/0.9) than in CO (1.18 +/- 0.2/0.03, P < 0.0001) groups. The (THF + 5alphaTHF)/THE ratio in CRF (1.19 +/- 1.1/0.5) and TX (1.19 +/- 0.1/0.5) groups was significantly higher than in controls (0.21 +/- 0.05/0.18, P < 0.0001). Positive correlations between plasma and urinary ratios (P = 0.0004. R(2) = 0.73 in CRF, P = 0.0013, R(2) = 0.56 in TX, P < 0.0001, R(2) = 0.66 in CO) were found, whereas significant correlations between F/E or (THF + 5alphaTHF)/THE ratios and blood pressure, the number of antihypertensive drugs taken or creatinine clearance could not be found.",
            "output": [
                "Does pediatric renal allograft transplantation normalize the increased cortisol/cortisone ratios of chronic renal failure?"
            ]
        },
        {
            "id": "task847-107bbc56962d41bd834cb736ec471bd3",
            "input": "Treatment options for metastases of differentiated thyroid carcinoma (DTC) are limited due to decreased uptake of radioiodide (I-131). Therefore, strategies to improve I-131 uptake are mandatory. It has been suggested that retinoids have beneficial effects on iodide uptake in vitro and in humans. However, to date, only studies with 13-cis-retinoic acid have been performed in humans. We therefore decided to study the effects of 6 weeks of treatment with the retinoid X receptor activator bexarotene on I-131 uptake in patients with metastatic DTC.', 'Open prospective intervention study.', 'Twelve patients with metastases of DTC, with insufficient uptake of I-131, received 6 weeks of treatment with 300 mg bexarotene/day. Prior to, and after this intervention, I-131 uptake was measured by whole-body scintigraphy and single photon emission tomography (SPECT) 3 days after 185 MBq I-131. Diagnostic imaging was preceded by two consecutive injections of recombinant human TSH.', 'Bexarotene treatment induced I-131 uptake in metastases of 8 out of 11 patients (one patient died for reasons not related to the study). However, uptake was only discernable at SPECT and had incomplete matching with metastases as visualized by CT scanning.",
            "output": [
                "Does bexarotene increase uptake of radioiodide in metastases of differentiated thyroid carcinoma?"
            ]
        },
        {
            "id": "task847-84a54430e8254bdfa29f74c67d46bf29",
            "input": "In patients undergoing total knee replacement (TKR), most blood loss occurs post-operatively, and the return of unwashed filtered shed blood (USB) from post-operative drainage may represent an alternative to allogeneic blood transfusion (ABT). We evaluated the impact of USB return on the cellular immune response (CIR) after TKR.', 'Forty TKR patients, intended to receive post-operative USB, entered the study. Blood samples were obtained before and 6 h, 24 h, 72 h and 7 days after surgery, and from USB, after it had been passed through a 40-microm filter. Full blood cell counts, lymphocyte subsets and immunoglobulins (IgA, IgG, IgM) were measured in all samples. A set of clinical data was collected from each patient.', 'Twenty-four of the 25 patients received a mean of 1.2 USB units and did not need additional ABT (USB group). Twelve of the 15 remaining patients who received neither USB nor ABT served as a control group for the post-operative CIR study. All patients showed a post-operative decrease in T-cell and natural killer (NK) cell counts, but not B-cell counts, and there were no significant differences between the groups with regard to CIR parameters, post-operative infection or hospital stay.",
            "output": [
                "Does post-operative unwashed shed blood transfusion modify the cellular immune response to surgery for total knee replacement?"
            ]
        },
        {
            "id": "task847-0484ff9fb77443f58f19026e07ec8c14",
            "input": "The susceptibility of neonates to pulmonary and systemic infection has been associated with the immaturity of both lung structure and the immune system. Surfactant protein (SP) D is a member of the collectin family of innate immune molecules that plays an important role in innate host defense of the lung.', 'We tested whether treatment with recombinant human SP-D influenced the response of the lung and systemic circulation to intratracheally administered Escherichia coli lipopolysaccharides.', 'After intratracheal lipopolysaccharide instillation, preterm newborn lambs were treated with surfactant and ventilated for 5 h.', 'Survival rate, physiologic lung function, lung and systemic inflammation, and endotoxin level in plasma were evaluated.', 'In control lambs, intratracheal lipopolysaccharides caused septic shock and death associated with increased endotoxin in plasma. In contrast, all lambs treated with recombinant human SP-D were physiologically stable and survived. Leakage of lipopolysaccharides from the lungs to the systemic circulation was prevented by intratracheal recombinant human SP-D. Recombinant human SP-D prevented systemic inflammation and decreased the expression of IL-1beta, IL-8, and IL-6 in the spleen and liver. Likewise, recombinant human SP-D decreased IL-1beta and IL-6 in the lung and IL-8 in the plasma. Recombinant human SP-D did not alter pulmonary mechanics following endotoxin exposure. Recombinant human SP-D was readily detected in the lung 5 h after intratracheal instillation.",
            "output": [
                "Does intratracheal recombinant surfactant protein d prevent endotoxin shock in the newborn preterm lamb?"
            ]
        },
        {
            "id": "task847-bd90e17e8ef342e1903dfa5280f459b6",
            "input": "We sought to investigate the effect of cardiac medication on long-term mortality in patients with peripheral arterial disease (PAD).', 'Peripheral arterial disease is associated with increased cardiovascular morbidity and mortality. Treatment guidelines recommend aggressive management of risk factors and lifestyle modifications. However, the potential benefit of cardiac medication in patients with PAD remains ill defined.', 'In this prospective observational cohort study, 2,420 consecutive patients (age, 64 +/- 11 years, 72% men) with PAD (ankle-brachial index < or =0.90) were screened for clinical risk factors and cardiac medication. Follow-up end point was death from any cause. Propensity scores for statins, beta-blockers, aspirin, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, diuretics, nitrates, coumarins, and digoxin were calculated. Cox regression models were used to analyze the relation between cardiac medication and long-term mortality.', 'Medical history included diabetes mellitus in 436 patients (18%), hypercholesterolemia in 581 (24%), smoking in 837 (35%), hypertension in 1,162 (48%), coronary artery disease in 1,065 (44%), and a history of heart failure in 214 (9%). Mean ankle-brachial index was 0.58 (+/-0.18). During a median follow-up of eight years, 1,067 patients (44%) died. After adjustment for risk factors and propensity scores, statins (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.36 to 0.58), beta-blockers (HR 0.68, 95% CI 0.58 to 0.80), aspirins (HR 0.72, 95% CI 0.61 to 0.84), and ACE inhibitors (HR 0.80, 95% CI 0.69 to 0.94) were significantly associated with a reduced risk of long-term mortality.",
            "output": [
                "Is cardioprotective medication associated with improved survival in patients with peripheral arterial disease?"
            ]
        },
        {
            "id": "task847-3cf8dce314634bf080d78cec00cc9037",
            "input": "To examine whether the Vulnerable Elders Survey (VES-13) score predicts risk of death and functional decline in vulnerable older adults.', 'Longitudinal evaluation with mean follow-up of 11 months (range 8-14 months).', 'Two managed care organizations in the United States.', 'Four hundred twenty community-dwelling older people identified as having moderate to high risk of death and functional decline based on a VES-13 score of 3 or higher. These older people were enrolled in the Assessing Care of Vulnerable Elders observational study.', 'Baseline: VES-13 score, sex, income, cognitive score, and number of medical diagnoses.', 'functional decline and death.', 'VES-13 scores strongly predicted death and functional decline (P<.001, area under the receiver operating curve=0.66). The estimated combined risk of death and decline rose with VES-13 score, increasing from 23% for older people with a VES-13 score of 3 to 60% for those with a score of 10. Other measures (sex, comorbidity) were not significant predictors of death or decline over this period after controlling for VES-13 score.",
            "output": [
                "Do higher vulnerable elders survey scores predict death and functional decline in vulnerable older people?"
            ]
        },
        {
            "id": "task847-d5551bf75a3a455d95d0a54f1f96a773",
            "input": "To determine whether metabolic syndrome is an independent predictor of decline in mobility in an elderly community sample.', 'Biracial community-based prospective cohort study.', 'Urban and rural areas of central North Carolina.', 'One thousand two hundred twenty-nine older African Americans and whites, mean age 77.0, who were participants in the Duke Established Populations for Epidemiologic Studies of the Elderly.', 'Sociodemographic data and data on mobility (a subset of items from the Rosow-Breslau scale), depression (Center for Epidemiological Studies Depression Scale), self-report of medical conditions, body mass index, cognitive function (Short Portable Mental Status Questionnaire), blood pressure, height, and waist circumference. High-density lipoprotein cholesterol, triglycerides, and blood glucose were available from blood samples. Metabolic syndrome was calculated for subjects with complete data.', 'Twenty-nine percent of the sample met criteria for metabolic syndrome. In bivariate analyses, age, sex, race, education, cognitive impairment, depression, impairment in mobility, history of stroke and heart disease, and metabolic syndrome at baseline were associated with a decline in mobility 4 years later. Regression analysis controlling for the above variables demonstrated that metabolic syndrome persisted as an independent and highly significant predictor of decline in mobility.",
            "output": [
                "Does metabolic syndrome predict mobility decline in a community-based sample of older adults?"
            ]
        },
        {
            "id": "task847-ea4aeb3a4a1f4a78ae10bf3f824d0435",
            "input": "Recent reports have described dramatic alterations in mitochondrial morphology during metazoan apoptosis. A dynamin-related protein (DRP) associated with mitochondrial outer membrane fission is known to be involved in the regulation of apoptosis. This study analysed the relationship between mitochondrial fission and regulation of plant cell death.', 'Transgenic plants were generated possessing Arabidopsis DRP3B (K56A), the dominant-negative form of Arabidopsis DRP, mitochondrial-targeted green fluorescent protein and mouse Bax.', 'Arabidopsis plants over-expressing DRP3B (K56A) exhibited long tubular mitochondria. In these plants, mitochondria appeared as a string-of-beads during cell death. This indicates that DRP3B (K56A) prevented mitochondrial fission during plant cell death. However, in contrast to results for mammalian cells and yeast, Bax-induced cell death was not inhibited in DRP3B (K56A)-expressing plant cells. Similarly, hydrogen peroxide-, menadione-, darkness- and salicylic acid-induced cell death was not inhibited by DRP3B (K56A) expression.",
            "output": [
                "Does the mitochondrial fission regulator DRP3B regulate cell death in plants?"
            ]
        },
        {
            "id": "task847-e0975e471de94efd99b1a8ddc109bed9",
            "input": "Fatty acid ethyl esters are ethanol metabolites inducing sustained, toxic elevations of the acinar cytosolic free calcium ion concentration ([Ca(2+)](C)) implicated in pancreatitis. We sought to define the mechanisms of this elevation.', 'Isolated mouse pancreatic acinar cells were loaded with fluorescent dyes for confocal microscopy to measure [Ca(2+)](C) (Fluo 4, Fura Red), endoplasmic reticulum calcium ion concentration ([Ca(2+)](ER), Mg Fluo 4), mitochondrial membrane potential (TMRM), ADP:ATP ratio (Mg Green), and NADH autofluorescence in response to palmitoleic acid ethyl ester and palmitoleic acid (10-100 micromol/L). Whole-cell patch clamp was used to measure the calcium-activated chloride current and apply ethanol metabolites and/or ATP intracellularly.', 'Intracellular delivery of ester induced oscillatory increases of [Ca(2+)](C) and calcium-activated currents, inhibited acutely by caffeine (20 mmol/L), but not atropine, indicating involvement of inositol trisphosphate receptor channels. The stronger effect of extracellular ester or acid caused depletion of [Ca(2+)](ER), not prevented by caffeine, but associated with depleted ATP, depleted NADH autofluorescence, and depolarized mitochondria, suggesting calcium-ATPase pump failure because of lack of ATP. Intracellular ATP abolished the sustained rise in [Ca(2+)](C), although oscillatory signals persisted that were prevented by caffeine. Inhibition of ester hydrolysis markedly reduced its calcium-releasing effect and consequent toxicity.",
            "output": [
                "Do fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis?"
            ]
        },
        {
            "id": "task847-e228f80690f6476f94fa8436900b5501",
            "input": "Brain-derived neurotrophic factor (BDNF) acts rapidly to modulate synaptic neurotransmission in the brain. Although present in neurons, glial cells, and mucosal cells of the colon, and in higher concentrations than in brain, the action of BDNF in gut have not been characterized. The aim of this study was to identify the role of BDNF in mediating the peristaltic reflex.', 'BDNF and a specific antiserum were examined for their effects on the peristaltic reflex and release of the sensory mediators serotonin and calcitonin gene-related peptide in rat colon. The peristaltic reflex and release of serotonin and calcitonin gene-related peptide were also examined in genetically modified mice (BDNF(+/-)) with reduced levels of BDNF.', 'Endogenous brain-derived neurotrophic factor was released into the sensory compartment in a stimulus-dependent manner during the peristaltic reflex induced by mucosal stimulation but not muscle stretch. BDNF stimulated and immunoneutralization of endogenous BDNF reduced ascending contraction and descending relaxation of circular muscle and release of serotonin and calcitonin gene-related peptide during the peristaltic reflex induced by mucosal stimulation but not muscle stretch. The peristaltic reflex and release of serotonin and calcitonin gene-related peptide during the peristaltic reflex induced by mucosal stimulation but not muscle stretch were significantly reduced in BDNF(+/-) mice.",
            "output": [
                "Does brain-derived neurotrophic factor augment peristalsis by augmenting 5-HT and calcitonin gene-related peptide release?"
            ]
        },
        {
            "id": "task847-96cf3d2bee2f496d987ee4655a86cff7",
            "input": "X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is a novel tumor suppressor and interferon (IFN)-stimulated gene. All-trans retinoic acid (ATRA) exerts an antiproliferative effect on tumor cells through up-regulation of IFN regulatory factor 1 (IRF-1) and the downstream IFN-stimulated genes. The aim of this study was to determine the effect and mechanism of ATRA on XAF1 expression and the role of XAF1 in ATRA-induced growth inhibition in colon cancer.', 'Gene expression is detected by reverse-transcription polymerase chain reaction and immunoblotting. The transcription activity of XAF1 promoter is examined by luciferase reporter assay. The activity of IFN regulatory factor binding element (IRF-E) is assessed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Cell growth is evaluated by both in vitro and in vivo in nude mice xenografts.', 'IFN-alfa stimulates XAF1 promoter activity in the colon cancer cells Lovo and SW1116 dose-dependently. An IRF-1 binding element (IRF-E-XAF1) is found in the -30 to -38 nucleotide region upstream of the ATG initiator codon of the XAF1 gene. Site-directed mutagenesis of IRF-E-XAF1 abrogates native and IFN-induced promoter activity and binding capacity. ATRA induces XAF1 expression both in vitro and in vivo through interaction with IRF-E-XAF1. Overexpression of XAF1 increases cell susceptibility to ATRA-induced growth suppression both in vitro and in vivo. Furthermore, the effect of ATRA on XAF1 expression is independent of the promoter methylation and the subcellular distribution of XIAP.",
            "output": [
                "Does all-trans retinoic acid induce XAF1 expression through an interferon regulatory factor-1 element in colon cancer?"
            ]
        },
        {
            "id": "task847-6d836c38cdeb4bc39e1abff57acc32ff",
            "input": "The purpose of this study was to investigate the expression of inflammatory cytokines TNF-alpha, IL-1beta, and IFN-gamma in the vitreous after experimentally induced endophthalmitis by a Staphylococcus epidermidis slime-producing strain.', 'Seventy-two experimental Lewis rats received an intravitreal injection of 7000 viable organisms of Staphylococcus epidermidis slime-producing ATCC strain 35983, while 72 control rats received an intravitreal injection of sterile normal saline. Eyes were graded daily for signs of clinical inflammation and were removed 6, 12, 24, 48, 72 h, and 7 days after injection. Vitreous was obtained and titers of TNF-alpha, IL-1beta, and IFN-gamma were measured with established enzyme-linked immunosorbent assays.', 'In the experimental group, the clinical inflammatory score reached maximum (4+) within 24 h, while inflammation was almost abolished by day 7 (score 0-0.5+). Statistically increased levels of TNF-alpha and IL-1beta were detected in the experimental vitreous with maximum levels observed at 12 h. IFN-gamma was also detected in the experimental vitreous and reached maximum levels at 48 h. None of the cytokines examined was detected in sera at any time point in experimental or control rats.",
            "output": [
                "Is expression of TNF-alpha , IL-1beta , and IFN-gamma in Staphylococcus epidermidis slime-positive experimental endophthalmitis closely related to clinical inflammatory scores?"
            ]
        },
        {
            "id": "task847-f420087538d246ae8e5b9f1b871481be",
            "input": "The treatment of persistent epithelial defects (PED) with autologous serum eye drops is often combined with conventional medication such as artificial tears and topical antibiotics, but until now no report exists on the use of a bandage contact lens (BCL) in combination with autologous serum eye drops in the treatment of PEDs. We report six eyes (five patients) which were all treated with autologous serum eye drops in combination with an FDA group IV hydrogel contact lens.', 'Five patients aged 36-88 years, were suffering from six PEDs for 73.5+/-46.9 days due to rheumatoid sterile corneal ulcer (n=1), neurotrophic keratopathy (n=3) or partial limbal stem cell deficiency (n=1). All patients had been unsuccessfully treated with conventional therapy before. Three of them had already had an amniotic membrane transplantation and two had undergone a keratoplasty; however, the epithelial defect persisted or recurred. In all cases, an FDA group IV hydrogel contact lens (Biomedics 55, ocufilcon D, 55% water content) was fitted and serum eye drops applied 8 times a day.', 'The PED healed in five of six eyes after a treatment period of 14.2+/-8.9 days. In one eye the PED became smaller, but it took 90 days until the lesion healed completely. In three eyes (two patients) white deposits appeared on the surface of the BCL during the treatment after 12.3+/-5.1 days. Because no signs of inflammation were observed and since the epithelial defect improved, a new identical lens was applied and the medication continued unaltered. The surface of contaminated and non-contaminated BCLs were analyzed by scanning electron microscopy and SDS gel-electrophoresis. The scanning electron microscopic examination presented a coating of amorphous material with a wrinkled appearance and many corpuscular deposits. There was no indication of bacterial colonisation. The SDS gel-electrophoresis showed a small band at 65 kDa, probably albumin.",
            "output": [
                "Does combination of serum eye drop with hydrogel bandage contact lenses in the treatment of persistent epithelial defects?"
            ]
        },
        {
            "id": "task847-db86580652aa431fb1a0782a1e1b650b",
            "input": "Flare up of acute lower back pain associated with myofascial pain syndrome (MPS) may require various forms of treatment including activity restriction and bracing. Electrical twitch obtaining intramuscular stimulation (ETOIMS) is a promising new treatment. It involves the use of a strong monopolar electromyographic needle electrode for electrical stimulation of deep motor end plate zones in multiple muscles in order to elicit twitches.', 'An elite American football player with MPS symptoms failed to respond to standard treatments. He then received ETOIMS which completely alleviated the pain. After establishing pain control, the athlete continued with a further series of treatments to control symptoms of muscle tightness.",
            "output": [
                "Do electrical twitch obtaining intramuscular stimulation ( ETOIMS ) for myofascial pain syndrome in a football player?"
            ]
        },
        {
            "id": "task847-4548d59b8c0540eeb18033e19a1db133",
            "input": "The present study was designed to give possible answers to some of the discrepancies regarding the presence or not of intact fetal cells in maternal plasma during pregnancy.', '12-mL peripheral blood was collected from 33 pregnant women in the second trimester: 6 mL was harvested by 3-step Percoll gradient centrifugation and plasma cells were analyzed by FISH with X/Y chromosome specific probes. From the remaining 6 mL, plasma-derived cells were isolated with three different gradient centrifugation protocols and apoptosis was determined following EthBr staining.', 'The number of cells recovered ranged from 900 to 3000. At least one Y positive signal was seen in 12 out of 17 cases with male fetuses at a frequency of 0.12% (range 0.05-0.27%). No XY cells were detected in the plasma of women carrying female fetuses. Hybridization efficiency was <60%. EthBr staining demonstrated that the majority of these cells were in their late apoptosis.",
            "output": [
                "Are fetal cells in maternal plasma found in a late state of apoptosis?"
            ]
        },
        {
            "id": "task847-3f09ea2e05e0417db1c8f57f7d7f8679",
            "input": "Knowledge of microbiology in the prognosis of patients with necrotizing pancreatitis is incomplete.', 'This study compared outcomes based on primary and secondary infection after surgery for pancreatic necrosis.', 'From a limited prospective database of pancreatic necrosectomy, a retrospective case note review was performed (October 1996 to April 2003).', '55 of 73 patients had infected pancreatic necrosis at the first necrosectomy. 25 of 47 patients had resistant bacteria to prophylactic antibiotics (n = 21) or did not receive prophylactic antibiotics (n = 4), but this was not associated with a higher mortality (9 of 25) compared to those with sensitive organisms (4 of 22). Patients with fungal infection (n = 6) had a higher initial median (95% CI) APACHE II score compared to those without (11 (9-13) verus 8.5 (7-10), p = 0.027). Five of six patients with fungal infection died compared to 13 of 47 who did not (p = 0.014). With the inclusion of secondary infections 21 (32%) of 66 patients had fungal infection with 10 (48%) deaths compared to 11 (24%) of 45 patients without fungal infection (p = 0.047).",
            "output": [
                "Is fungal infection but not type of bacterial infection associated with a high mortality in primary and secondary infected pancreatic necrosis?"
            ]
        },
        {
            "id": "task847-5200814b699441e99c1e17c63c710437",
            "input": "Smoking, largely through increased oxidative stress, causes endothelial dysfunction which is an early key event in atherosclerosis. Smoking cessation and antioxidant vitamin therapy are shown to have beneficial role by restoring altered endothelial physiology. The present study was aimed to determine whether Terminalia arjuna, an Indian medicinal plant with potent antioxidant constituents, would improve endothelial dysfunction in smokers.', 'Eighteen healthy male smokers (age 28.16+/-9.45 years) and equal number of age-matched non-smoker controls participated in the study. The baseline brachial artery reactivity studies were performed using high frequency ultrasound according to standard protocol under identical conditions to determine endothelium-dependent, flow-mediated dilation and endothelium-independent nitroglycerine-mediated dilation. The two groups were matched regarding age, body mass index, blood pressure, serum cholesterol, mean resting vessel diameters and post-occlusion flow velocities (all p=NS). While flow-mediated dilation was significantly impaired amongst smokers compared to controls (4.71+/-2.22 v. 11.75+/-5.94%, p <0.005), the nitroglycerine-mediated dilation was similar in the two groups (20.35+/-3.89 v. 19.68+/-3.74%, p=NS). Subsequently the smokers were given Terminalia arjuna (500 mg q8h) or matching placebo randomly in a double blind cross-over design for two weeks each, followed by repetition of brachial artery reactivity studies to determine various parameters including flow-mediated dilation after each period. There was no significant difference as regards vessel diameter and flow velocities between the two therapies. However, the flow-mediated dilation showed significant improvement from baseline values after Terrminalia arjuna therapy but not with placebo (9.31+/-3.74 v. 5.17+/-2.42%, p <0.005).",
            "output": [
                "Does terminalia arjuna reverse impaired endothelial function in chronic smokers?"
            ]
        },
        {
            "id": "task847-20650ddeea2e49169a21e4e80e11b6b0",
            "input": "There is an increasing knowledge that the severity of perennial allergic rhinitis is associated with nasal carriage of Staphylococcus aureus (S. aureus). The aim of this study was to evaluate the rate of bacterial colonization with S. aureus in the nose of subjects with and without chronic rhinosinusitis (CRS) and to correlate these findings with the severity of symptoms and the extent of the disease.', 'Open, prospective controlled trial.', \"190 subjects with CRS and 42 subjects with septal deviation without sinusitis (control subjects) were included in this study. Swabs were taken endoscopically from the middle meatus and bacteria were cultured and identified. Airway symptoms were assessed by subjects in standardized questionnaires and frequencies of respiratory tract infections were noted. The rhinosinusitis extent was graded by CT scan assessment. Analysis of variance, chi-square test, and Pearson's correlation test were applied for statistical analyses.\", 'The S. aureus carriage rate was 25.5% in CRS and 31.4% in control subjects. Further facultative pathogens were cultured in 20.6% of subjects with CRS and in 8.5% of controls. 73.8% of S. aureus were ampicillin-resistant, multiresistant strains were cultured in 5.8%. Most airway symptoms and the frequencies of respiratory tract infections were significantly higher in the CRS group compared with control subjects. In post hoc comparison between the subgroups with and without S. aureus colonization, no significant differences were found between the extent of rhinosinusitis and the severity of airway symptoms.",
            "output": [
                "Is nasal colonization with Staphylococcus aureus associated with the severity of symptoms or the extent of the disease in chronic rhinosinusitis?"
            ]
        },
        {
            "id": "task847-9f55e1d02c7146f39e088e1ee0d62569",
            "input": "To evaluate the efficacy of continuous low-level heat wrap therapy for the treatment of various sources of wrist pain including strain and sprain (SS), tendinosis (T), osteoarthritis (OA), and carpal tunnel syndrome (CTS).', 'Prospective, randomized, parallel, single-blind (investigator), placebo-controlled, multicenter clinical trial.', 'Two community-based research facilities.', 'Ninety-three patients (age range, 18-65 y) with wrist pain.', 'Subjects with moderate or greater wrist pain were randomized and stratified to 1 of the following treatments: efficacy evaluation (heat wrap, n=39; oral placebo, n=42) or blinding (oral acetaminophen, n=6; unheated wrap, n=6). Data were recorded over 3 days of treatment and 2 days of follow-up.', 'The primary comparison was between the heat wrap and the oral placebo group among SS/T/OA subjects for pain relief. Outcome measures included pain relief (0-5 scale), joint stiffness (101-point numeric rating scale), grip strength measured by dynamometry, and perceived pain and disability (Patient Rated Wrist Evaluation [PRWE]); subjects with CTS also completed the Symptom Severity Scale and Functional Status Scale.', 'Heat wrap therapy showed significant benefits in day 1 to 3 mean pain relief (P=.045) and increased day 3 grip strength (P=.02) versus oral placebo for the SS/T/OA group. However, joint stiffness and PRWE results were comparable between the 2 treatments. For the CTS group, heat wraps provided greater day 1 to 3/hour 0 to 8 mean pain relief (P=.001), day 1 to 3 mean joint stiffness reduction (P=.004), increased day 3 grip strength (P=.003), reduced PRWE scores (P=.0015), reduced symptom severity (P=.001), and improved functional status (P=.04). In addition, the heat wrap showed significant extended benefits through follow-up (day 5) in the CTS group.",
            "output": [
                "Is continuous low-level heat wrap therapy effective for treating wrist pain?"
            ]
        },
        {
            "id": "task847-2a76ee1f7f704f63b8499b40adffbff6",
            "input": "Chronic marijuana use has been associated with impairments of learning, memory, and executive functions. Little is known, however, about the effects of marijuana use on other cognitive domains, such as decision-making, which are thought to play an important role in addiction and drug abuse.', 'The purpose of the present study was to determine if long-term heavy marijuana users employ different decision-making strategies than individuals with minimal marijuana exposure.', 'Volunteers were assigned to a cannabis (n = 10) or control group (n = 10) based upon history of prior marijuana use. Demographic and neuropsychological variables were evaluated, and a decision-making task--the gambling task (GT) was administered.', 'Although few demographic and neuropsychological differences were noted between groups, marijuana users made more decisions that led to larger immediate gains despite more costly losses than controls.",
            "output": [
                "Do long-term heavy marijuana users make costly decisions on a gambling task?"
            ]
        },
        {
            "id": "task847-9dc2129b19624585baaacff5f5a7c654",
            "input": "Microvascular alterations contribute to the development of stroke and vascular dementia. The goal of this study was to evaluate age and hypertension related changes of the basal lamina in cerebral microvessels of individuals, who died from non-cerebral causes.', 'We examined 27 human brains: 11 young and 16 old patients. Old patients were divided into two subgroups, those with hypertension (n = 8) and those without hypertension (n = 8). Basal lamina changes of the cerebral microvessels were determined in the putamen using antibodies against collagen type IV and by quantitative analysis of vessel number, total stained area of collagen, thickness of the vessel wall and lumen, and relative staining intensity using immunofluorescence. The total number of collagen positive vessels per microscopic field was reduced in old compared to young subjects (12.0+/-0.6 vs. 15.1+/-1.2, p = 0.02). The relative collagen content per vessel (1.01+/-0.06 vs. 0.76+/-0.05, p = 0.01) and the relative collagen intensity (233.1+/-4.5 vs. 167.8+/-10.6, p < 0.0001) shown by immunofluorescence were higher in the older compared to the younger patients with a consecutive reduction of the lumen / wall ratio (1.29+/-0.05 vs. 3.29+/-0.15, p < 0.0001). No differences were observed for these parameters between old hypertensive and non-hypertensive patients.",
            "output": [
                "Is aging associated with increased collagen type IV accumulation in the basal lamina of human cerebral microvessels?"
            ]
        },
        {
            "id": "task847-8cc92a4be0ce4da8940d4b67c25b9a31",
            "input": "Angiogenesis gene therapy with human tissue kallikrein (hTK) has shown promise for ischemic disease. The present study was undertaken to (1) assess an optimal gene transfer modality, (2) clarify hTK angiogenic pathways, and (3) discount possible side effects.', 'The hTK gene was transferred to murine adductors by increasing doses of an adenovirus (Ad.hTK). Heterologous protein production was evaluated by ELISA and immunohistochemistry. Structural and functional characteristics of hTK-induced neovascularization were assessed. Muscular endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF)-A mRNA and protein content were evaluated by real-time polymerase chain reaction and Western blotting. The ability of hTK to phosphorylate-activate Akt/protein kinase B (Akt-B) and VEGF receptor 2 (VEGF-R2) was also determined. Implication of the aforementioned mechanisms in Ad.hTK-induced neovascularization was challenged by blocking Akt-B with a dominant-negative Akt construct; NOS with N(G)-nitro-L-arginine methyl ester; and VEGF-A with neutralizing antibody, VEGF-R2 antagonist, or Ad carrying soluble VEGF-R1 gene. We found that 10(7) PFU Ad.hTK led to peak increases in capillary and arteriole density. Newly developed arterioles persisted for up to 8 weeks. Ad.hTK did not change microvascular permeability. Ad.hTK upregulated eNOS mRNA and protein and activated Akt-B through Ser-473 phosphorylation. Inhibitory studies documented that these biochemical events were instrumental to Ad.hTK-induced neovascularization. In contrast, Ad.hTK neither affected VEGF-A and VEGF-R2 levels nor increased VEGF-R2 phosphorylation. Consistently, Ad.hTK-induced neovascularization was not disturbed by any of the different approaches used to block VEGF-A.",
            "output": [
                "Do akt/protein kinase B and endothelial nitric oxide synthase mediate muscular neovascularization induced by tissue kallikrein gene transfer?"
            ]
        },
        {
            "id": "task847-919792d1efe44403b0093c07a1be39bc",
            "input": "Elevated circulating aldosterone level is associated with impaired cardiovascular function. Although the mechanisms are not fully understood, aldosterone antagonists decrease total and cardiovascular mortality in heart failure and myocardial infarction. Aldosterone induces cardiac fibrosis in experimental models, and it is synthesized locally in rat heart. These observations suggest pathological effects of aldosterone in heart that remain unclear.', 'Transgenic mice (TG) that overexpress the terminal enzyme of aldosterone biosynthesis, aldosterone synthase (AS), in heart have been raised by gene targeting with the alpha-myosin heavy chain promoter. AS mRNA increased 100-fold and aldosterone concentration 1.7-fold in hearts of male TG mice relative to wild-type. No structural or myocardial alterations were evidenced, because ventricle/body weight, AT1 and AT2 receptor binding, and collagen content were unchanged in TG. No alteration in cardiac function was evidenced by echocardiography, isolated perfused heart, or whole-cell patch clamp experiments. In contrast, coronary function was impaired, because basal coronary flow was decreased in isolated perfused heart (-55% of baseline values), and vasodilatation to acetylcholine, bradykinin, and sodium nitroprusside was decreased by 75%, 60%, and 75%, respectively, in TG mice compared with wild-type, showing that the defect was not related to NO production.",
            "output": [
                "Does cardiac specific increase in aldosterone production induce coronary dysfunction in aldosterone synthase-transgenic mice?"
            ]
        },
        {
            "id": "task847-14cee467da8c4e6bb5b3c8c031a23c50",
            "input": "Evidence suggests that induction of heme oxygenase-1 (HO-1) inhibits proliferation of vascular smooth muscle cells and intimal thickening after arterial injury, and therapeutic molecules induce HO-1. Probucol is the only oral drug that inhibits restenosis in humans and intimal thickening in animals, although its underlying mechanism remains unclear.', 'Aortas were harvested from New Zealand White rabbits fed normal or 0.75% (wt/wt) probucol-fortified chow, with or without endothelial denudation of the abdominal aorta on day 21, and analyzed for heme oxygenase and apoptosis. Uninjured aortas were harvested on day 21 and balloon-injured aortas on days 22 and 25. Probucol significantly increased mRNA of HO-1 assessed by real-time PCR and HO activity in aortas at all time points. Probucol also enhanced apoptosis of medial cells in the injured aorta, as evidenced by the TUNEL assay. Furthermore, probucol (100 micromol/L) increased HO-1 mRNA and HO activity when added to rabbit aortic smooth muscle cells (RASMCs) cultured in serum-free medium for 24 hours. Induction of HO-1 mRNA was inhibited by actinomycin D and was associated with inhibition of RASMC proliferation. This probucol-induced increase in HO-1 mRNA and inhibition of RASMC proliferation was prevented by the HO inhibitor Sn(IV) protoporphyrin or transfection with small interference RNA (siRNA) to knockdown HO-1, but not by inactive Cu(II) protoporphyrin or scrambled siRNA.",
            "output": [
                "Does probucol protect against smooth muscle cell proliferation by upregulating heme oxygenase-1?"
            ]
        },
        {
            "id": "task847-ef182142a0b04c6fa9c5eda362a0f49b",
            "input": "The persistence of human immunodeficiency virus (HIV) type 1 within resting CD4+ T cells poses a daunting therapeutic challenge. Histone deacetylase (HDAC)-1, a chromatin-remodeling enzyme that can mediate gene silencing, is recruited to the HIV-1 long terminal repeat by the host transcription factor LSF. Pyrrole-imidazole polyamides, small molecules that target specific DNA sequences, can access the nucleus of cells and specifically block transcription-factor binding.', 'We used polyamides to directly test the role of chromatin remodeling in HIV quiescence in primary resting CD4+ T cells obtained from HIV-infected patients.', \"After exposure to any of 4 different polyamides that specifically block HDAC-1 recruitment by LSF to the HIV promoter, replication-competent HIV was recovered from cultures of resting CD4+ T cells in 6 of 8 HIV-infected patients whose viremia had been suppressed by therapy. In comparison, HIV was not recovered after exposure to control, mismatched polyamides but was recovered from 7 of 8 of these patients' samples after the activation of T cells.",
            "output": [
                "Do polyamides reveal a role for repression in latency within resting T cells of HIV-infected donors?"
            ]
        },
        {
            "id": "task847-cb62f5fc18cc4e75979132d51cbf6ecb",
            "input": "Obstructive uropathy is a significant clinical problem that results in apoptotic renal cell death and progressive renal fibrosis. A number of different inflammatory mediators have been implicated in the pathophysiology of obstruction induced renal injury including tumor necrosis factor-alpha (TNF)-alpha. The cellular source of obstruction induced renal TNF-alpha production and its relationship to renal inflammatory cell infiltration remain unknown.', 'Male Sprague-Dawley rats were anesthetized and exposed to varying lengths of unilateral ureteral obstruction vs sham operation. The kidneys were harvested following renal injury and evaluated for TNF-alpha mRNA expression (reverse transcriptase polymerase chain reaction), TNF-alpha protein production (enzyme-linked immunosorbent assay), TNF-alpha cellular localization (immunohistochemistry) and leukocyte infiltration (leukocyte staining).', 'Renal TNF-alpha mRNA expression and protein production peaked following 3 days of ureteral obstruction (54 +/- 5% vs sham 22 +/- 9% of glyceraldehyde-3-phosphate dehydrogenase mRNA, p <0.05 and 204 +/- 13 vs sham 84 +/- 9 pg/ml, p <0.05, respectively). TNF-alpha production localized primarily to renal cortical tubular cells following obstruction and the time point of maximal TNF-alpha production (3 days of obstruction) were not associated with a significant renal inflammatory cell infiltrate.",
            "output": [
                "Does unilateral ureteral obstruction induce renal tubular cell production of tumor necrosis factor-alpha independent of inflammatory cell infiltration?"
            ]
        },
        {
            "id": "task847-20bf7f01af3f405d998a1cd1e1fb6aa0",
            "input": "To explore the role of hepatitis C virus (HCV) envelope protein 2 (E2) in the induction of apoptosis.', 'A carboxyterminal truncated E2 (E2-661) was transiently expressed in several cultured mammalian cell lines or stably expressed in Chinese hamster ovary (CHO) cell line. Cell proliferation was assessed by 3H thymidine uptake. Apoptosis was examined by Hoechst 33258 staining, flow cytometry and DNA fragmentation analysis.', 'Reduced proliferation was readily observed in the E2-661 expressing cells. These cells manifested the typical features of apoptosis, including cell shrinkage, chromatin condensation and hypodiploid genomic DNA content. Similar apoptotic cell death was observed in an E2-661 stably expressing cell line.",
            "output": [
                "Does expression of hepatitis C virus envelope protein 2 induce apoptosis in cultured mammalian cells?"
            ]
        },
        {
            "id": "task847-afc876cf465e40319bcf34b0d4b15766",
            "input": "To assess the relationship between congenital uterine malformations and blood pressure in pregnancy.', 'Twenty-four-hour automated ambulatory blood pressure monitoring (readings every 30 min) was performed in 16 normotensive, nonproteinuric, primigravidae with congenital uterine malformations (5 uterus septus, 9 uterus bicornis, 2 uterine didelphys) between 20 and 30 weeks. From the 24-hr blood pressure report, we calculated 24-hr mean, daytime and nighttime means. The results were compared with 16 primigravidae, matched for age and gestation, who were and remained normotensive throughout pregnancy, and tested for statistics with t-test; significance assessed at p < 0.001.', 'Although they were within the normotensive range, all blood pressure measurements considered were significantly higher in pregnant women with congenital uterine malformations, compared to normal pregnant women. Namely, 24-hr, daytime, and nighttime systolic (mean +/- SD) were 121.1 +/- 8.4, 124.4 +/- 8.8, 114.0 +/- 7.7 mmHg, respectively, in women with uterine malformations and 108.0 +/- 7.4, 109.2 +/- 7.3, 102.1 +/- 8.5 mmHg, respectively, in normal pregnant women. Twenty-four-hour diastolic, daytime, and nighttime diastolic (mean +/- SD) 74.1 +/- 10.2, 77.1 +/- 10.6, 68.1 +/- 9.2 mmHg, in women with uterine malformations and 64.1 +/- 5.7, 66.0 +/- 5.7, 58.2 +/- 6.3 mmHg, in normal pregnant women (all differences p < 0.001). Fifteen of the fetuses from women with congenital uterine malformations showed intrauterine growth retardation. No differences were found 6 months after delivery.",
            "output": [
                "Are congenital uterine malformations associated to increased blood pressure in pregnancy?"
            ]
        },
        {
            "id": "task847-dfa6933a688b4198994c8918b6a07f55",
            "input": "Adenovirus binds to the coxsackievirus and adenovirus receptor (CAR) as a first step in the process of cellular infection. This dependence on CAR potentially limits the use of adenovirus in gene therapy, since CAR is expressed in many tissues of the body, and expression of CAR may be low or lost upon progression of certain tumors. These limitations may be overcome by transductional targeting of adenovirus towards other cell surface molecules. We have evaluated the pantumoral epithelial cell adhesion molecule (EpCAM) and prostate specific membrane antigen (PSMA) as possible targets for adenoviral transduction of prostate cancer cells.', \"Bispecific antibodies, constructed as conjugates between an anti-adenovirus fiber knob Fab' fragment and anti-EpCAM or anti-PSMA monoclonal antibodies, were incubated with an eGFP-expressing adenovirus to retarget this vector. A cell panel, that includes two prostate cancer cell lines and four non-prostate control lines, were infected with serial dilutions of the retargeted vector and specificity of infection was determined.\", 'Receptor-specific transduction was obtained for both EpCAM and PSMA. PSMA-retargeting was shown to be selective for the prostate cancer cell lines.",
            "output": [
                "Is prostate specific membrane antigen ( PSMA ) a tissue-specific target for adenoviral transduction of prostate cancer in vitro?"
            ]
        },
        {
            "id": "task847-a8854cd203c64ccabffdf0d1145a8c42",
            "input": "Plasma levels of adrenomedullin, a potent vasodilator peptide, are increased in cirrhotic patients, whereas its role in vascular hyporeactivity in cirrhosis has not been clarified.', 'Adrenomedullin expression was evaluated by radioimmunoassay and reverse-transcription polymerase chain reaction. Vascular reactivity to phenylephrine, alpha-adrenoceptor agonist, was investigated in the aortic rings from control rats and CCl-induced cirrhotic rats with ascites in the presence of the neutralizing antibody against adrenomedullin, human adrenomedullin and/or N-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor.', 'Plasma adrenomedullin levels were significantly higher in cirrhotic rats than in controls (16.3 +/- 2.9 versus 7.4 +/- 1.7 fmol/mL, P < 0.05) and correlated negatively with systemic arterial pressure (r = -0.62, P < 0.05). Gene expression of adrenomedullin in various organs (liver, kidney, lung) and vessels (portal vein, aorta) was enhanced in cirrhotic rats compared with controls. Neutralizing antibody against adrenomedullin ameliorated the blunted contractile response to phenylephrine in cirrhotic aorta (Rmax: 1.5 +/- 0.1 versus 1.0 +/- 0.1 g/mg tissue, P < 0.05), whereas contraction remained unchanged in control aorta (Rmax: 1.9 +/- 0.2 versus 1.9 +/- 0.2 g/mg tissue). Intravenous infusion of human adrenomedullin induced a reduction of mean arterial pressure together with an increase of serum nitrate levels, which was abolished by neutralizing antibody against adrenomedullin. Human adrenomedullin caused a blunted contractile response to phenylephrine in both control and cirrhotic aortas, which was not observed in the presence of N-nitro-L-arginine methyl ester.",
            "output": [
                "Does adrenomedullin contribute to vascular hyporeactivity in cirrhotic rats with ascites via a release of nitric oxide?"
            ]
        },
        {
            "id": "task847-4503f0f2900e4fbc8af351a74c20d2be",
            "input": "Recent research has reported that high sugar diets increase insulin resistance, without abdominal obesity, in male, but not female Wistar rats. Whether a high sucrose (SU) diet increased insulin resistance in ovariectomized (OVX) rats was determined.', 'Female Sprague Dawley rats, weighing 273 +/- 20 g, had either an ovariectomy or a sham operation (sham). OVX and sham rats were divided into two groups: one group had a 68 En% SU diet and the other a 68 En% starch (ST) diet for 8 weeks.', 'The body weight was higher in the OVX than the sham rats, regardless of dietary carbohydrate subtype. The fasting serum glucose levels did not differ according to diet and ovariectomy. However, the fasting serum insulin levels were higher in the OVX than the sham rats, and in the OVX rats, a high SU diet increased the serum insulin levels more than a high ST diet. The whole body glucose disposal rates, which referred to the state of insulin sensitivity, were lower in the OVX rats fed both the high SU and ST diets, compared to sham rats. Glycogen deposits in the soleus and quadriceps muscles were lower in the OVX rats fed high SU and ST diets than in sham rats. The glucose transporter 4 content and fraction velocity of glycogen synthase in muscles showed similar glucose disposal rates. However, the triacylglycerol content in the muscles were higher in the OVX rats with a high SU diet than those with a high ST diet.",
            "output": [
                "Does a high carbohydrate diet induce insulin resistance through decreased glucose utilization in ovariectomized rats?"
            ]
        },
        {
            "id": "task847-9c3c5a93511b4b93b55e7faac3698ec6",
            "input": "Unintentional intraneural injection of local anesthetics may cause mechanical injury and pressure ischemia of the nerve fascicles. One study in small animals showed that intraneural injection may be associated with higher injection pressures. However, the pressure heralding an intraneural injection and the clinical consequences of such injections remain controversial. Our hypothesis is that an intraneural injection is associated with higher pressures and an increase in the risk of neurologic injury as compared with perineural injection.', 'Seven dogs of mixed breed (15-18 kg) were studied. After general endotracheal anesthesia, the sciatic nerves were exposed bilaterally. Under direct microscopic guidance, a 25-gauge needle was placed either perineurally (into the epineurium) or intraneurally (within the perineurium), and 4 mL of lidocaine 2% (1:250,000 epinephrine) was injected by using an automated infusion pump (4 mL/min). Injection pressure data were acquired by using an in-line manometer coupled to a computer via an analog digital conversion board. After injection, the animals were awakened and subjected to serial neurologic examinations. On the 7th day, the dogs were killed, the sciatic nerves were excised, and histologic examination was performed by pathologists blinded to the purpose of the study.', 'Whereas all perineural injections resulted in pressures < or =4 psi, the majority of intraneural injections were associated with high pressures (25-45 psi) at the beginning of the injection. Normal motor function returned 3 hours after all injections associated with low injection pressures (< or =11 psi), whereas persistent motor deficits were observed in all 4 animals having high injection pressures (> or =25 psi). Histologic examination showed destruction of neural architecture and degeneration of axons in all 4 sciatic nerves receiving high-pressure injections.",
            "output": [
                "Does combination of intraneural injection and high injection pressure lead to fascicular injury and neurologic deficits in dogs?"
            ]
        },
        {
            "id": "task847-d9d3a7d9964640fc96889760942eccbf",
            "input": "To study the value of objective pressure-volume characteristics for predicting optimal airway pressures and the development of atelectasis and overstretching during a structured lung volume recruitment procedure with subsequent reduction in airway pressures.', 'We used a mathematical model of a lung with adjustable characteristics of acute respiratory distress syndrome (ARDS) characteristics. Simulations were performed in five grades of ARDS in the presence of pure alveolar or combined alveolar-small airway closure as well complete or incomplete lung volume recruitability. For each simulation optimal end-expiratory pressure was determined. A static pressure-volume curve was constructed and objective characteristics of this curve calculated. The predictive value of these characteristics for end-expiratory atelectasis, overstretching, and optimal end-expiratory pressure was assessed.', 'Simultaneous alveolar recruitment and overstretching during inflation were more pronounced than alveolar derecruitment and overstretching during deflation. End-expiratory pressure needed to prevent significant alveolar collapse in severe ARDS resulted in maximal safe tidal volumes that may be insufficient for adequate ventilation using conventional mechanical ventilatory modes. Plateau pressures well below the \"upper corner point\" (airway pressure where compliance decreases) resulted in significant alveolar overstretching.",
            "output": [
                "Are static pressure-volume curve characteristics moderate estimators of optimal airway pressures in a mathematical model of ( primary/pulmonary ) acute respiratory distress syndrome?"
            ]
        },
        {
            "id": "task847-ab82dbd37a83455299e7297194864d14",
            "input": "To determine whether a common peer assessment instrument can assess competencies across internal medicine, pediatrics, and psychiatry specialties.', \"A common 36 item peer survey assessed psychiatry (n = 101), pediatrics (n = 100), and internal medicine (n = 103) specialists. Cronbach's alpha and generalizability analysis were used to assess reliability and factor analysis to address validity.\", \"A total of 2,306 (94.8% response rate) surveys were analyzed. The Cronbach's alpha coefficient was.98. The generalizabililty coefficient (mean of 7.6 raters) produced an Ep(2) =.83. Four factors emerged with a similar pattern of relative importance for pediatricians and internal medicine specialists whose first factor was patient management. Communication was the first factor for psychiatrists.",
            "output": [
                "Do an examination of the appropriateness of using a common peer assessment instrument to assess physician skills across specialties?"
            ]
        },
        {
            "id": "task847-0b45a5b0c87f49af96b03e300061a4f5",
            "input": "Preeclampsia is a serious disorder of pregnancy characterized by hypertension, proteinuria, edema, and coagulation and vascular abnormalities. At the cellular level, abnormalities include increased calcium concentration in platelets, lymphocytes, and erythrocytes. Recent studies have shown that antibodies directed against angiotensin II type I (AT1) receptors are also highly associated with preeclampsia.', 'We tested the hypothesis that AT1 receptor-agonistic antibodies (AT1-AAs) could activate AT1 receptors, leading to an increased intracellular concentration of free calcium and to downstream activation of Ca2+ signaling pathways. Sera of 30 pregnant patients, 16 diagnosed with severe preeclampsia and 14 normotensive, were examined for the presence of IgG capable of stimulating intracellular Ca2+ mobilization. IgG from all preeclamptic patients activated AT1 receptors and increased intracellular free calcium. In contrast, none of the normotensive individuals had IgG capable of activating AT1 receptors. The specific mobilization of intracellular Ca2+ by AT1-AAs was blocked by losartan, an AT1 receptor antagonist, and by a 7-amino-acid peptide that corresponds to a portion of the second extracellular loop of the AT1 receptor. In addition, we have shown that AT1-AA-stimulated mobilization of intracellular Ca2+ results in the activation of the transcription factor, nuclear factor of activated T cells.",
            "output": [
                "Do antibodies from preeclamptic patients stimulate increased intracellular Ca2+ mobilization through angiotensin receptor activation?"
            ]
        },
        {
            "id": "task847-56304a42738a4ecda31ca9af9c03283e",
            "input": "The purpose of this paper is to determine the effectiveness of web-based video lectures on demand for the deaf in comparison to the traditional method of teaching using a sign language interpreter. The web-based lectures presented are specifically designed for the deaf in education and in rehabilitation.', \"Sixty-three deaf students and adults were divided into four groups. All of the groups were made up of users who shared similar knowledge in the field of computers, but with different abilities in using computers, from beginners to advanced users. All of the groups were of mixed gender. The first two groups (consisting of 23 test users) graded the usability of the user interface for web-based lecture on demand with the help of the standardized SUMI questionnaire. After that, two groups (20 students from high school and 20 adults) joined in a 45-min informational program on the history of the deaf. Both groups were then divided into two smaller subgroups of 10 participants. The first subgroup in the first part of the learning program followed a traditional teaching style with the help of a teacher and an interpreter for Slovenian sign language. Meanwhile, the second group observed a 12-min web-based video lecture on demand and still had available an additional 18 min for a more detailed observation of the video. At the end of the lecture, the teacher used the questionnaire to review the participants' understanding of the content of the lecture in both of the groups. During the entire testing period, the interpreter used Slovenian sign language.\", 'By using the SUMI questionnaire, we determined the usability of the user interface for comprehension and gathering of knowledge. We discovered that the system was usable according to the standards. The global Median results (Global Median=51) were in the range of 50. In the second part of testing, we determined the level of significance between the traditional and web-based lectures. The results were statistically evaluated using the t-tests and the ANOVA test. From the t-tests we established the hypothesis that the number of correct answers for both groups (group 1: web-based, group 2: traditional) differed. The t-test used for the age groups rejected the hypothesis that the number of correct answers for both groups differed, where group 1 was comprised of adults and group 2 was comprised of students. Additionally, the ANOVA test showed that the number of correct answers for adults using traditional lectures differed significantly from the number of correct answers for both adult and student web-based users. The ANOVA test showed no differences between any of the remaining groups.",
            "output": [
                "Does the role of video technology in on-line lecture for the deaf?"
            ]
        },
        {
            "id": "task847-3d62f789e23e4225ae2fd6a7cb460c0c",
            "input": "To investigate the expression levels of lymphocyte antigen 6 complex, locus E (LY6E) and interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) genes in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), and to evaluate the relations between these gene expression levels and disease activity.', 'The clinical data of 144 SLE patients, 27 non-SLE patients with rheumatic diseases, and 59 normal controls were collected. The SLE patients were further divided into 2 subgroups: active SLE group (n = 87) and non-active SLE group (n = 57) according to SLEDAI scores. Specimens of peripheral blood were drawn; total RNA was extracted and transcribed into cDNA. Sybr green dye based real-time quantitative PCR method was used to compare the expression levels (indicated as-DeltaDeltaCT value) of LY6E and IFIT1 in patients with SLE and those in the controls.', '(1) The-DeltaDeltaCT value of LY6E expression level of the SLE patients was 5.4760 +/- 1.9806, significantly higher than those of the non-SLE patients (3.4323 +/- 1.7456) and normal controls (4.5198 +/- 1.6359, both P = 0.001). (2) The-DeltaDeltaCT value of LY6E and IFIT1 mRNA expression of the active SLE patients were 6.1960 +/- 1.7729 and 6.4997 +/- 2.6297 respectively, significantly higher than those observed in the inactive SLE patients (4.3770 +/- 1.7764 and 4.1327 +/- 2.6044 respectively, both P = 0.000). The-DeltaDeltaCT values of LY6E and IFIT1 mRNA of the SLE patients were correlated with the SLEDAI scores, and with the numbers of matched criteria used in the diagnosis of SLE (P < 0.001).",
            "output": [
                "Are [ Interferon-inducible genes lymphocyte antigen 6 complex E and tetratricopeptide repeats 1 correlated with clinical features of patients with systemic lupus erythematosus ]?"
            ]
        },
        {
            "id": "task847-a977d2a9197a4702a4c6b7a776f75d17",
            "input": "Results from GOG 178 showed a prolongation of progression-free survival (PFS) with the immediate use of chemotherapy (CT) following a complete clinical response (CR) in patients with stage III-IV ovarian cancer. We wanted to evaluate our strategy of reserving second line (2nd line) chemotherapy to the time of clinical recurrence by determining PFS intervals following first, second, and third line agents and to compare these finding to results of GOG 178.', 'We conducted a retrospective parallel study to GOG 178 using identical criteria for PFS definitions. Patients (pts) with stage III-IV cancer achieving a CR following surgery and five to eight cycles of platinum-based CT were identified. Patients not obtaining a CR and those with a CR who underwent second look surgery were excluded. Rather than immediately beginning consolidation CT after CR, second line agents were started at recurrence and were followed by a third line when pts progressed. Clinical-pathologic characteristics were abstracted, and time intervals including time to recurrence, time to use of second line CT, time to use of third line (3rd line) CT, and survival were recorded. Time intervals were studied by Kaplan-Meier method.', 'Of 217 reviewed pts (1991-2001), 59 eligible pts were identified. Forty-nine patients had stage III disease and ten had stage IV. At completion of surgery, 44 were optimally debulked. With a median follow-up of 51 months, the median PFS (from CR) of all patients was 20 months. At 5 years, 36% of pts remain disease-free, and 66% of pts are alive. Twenty-three pts have not received second line agents, and thirty-six have received them. For all pts, the median time from CR to start of second line chemotherapy was 21 months, and the median time to start of third line agents was 43 months. Recurrences occurred after 6 months from completion of first line (1st line) therapy in 87% of cases and after 12 months in 50%.",
            "output": [
                "Is timing n't everything : an analysis of when to start salvage chemotherapy in ovarian cancer?"
            ]
        },
        {
            "id": "task847-54c84e19f5a24e6c988bea503b815f82",
            "input": "Previous studies have demonstrated deregulation of the expression and changes in the intracellular distribution of TGF-beta pathway components in human endometrial cancer (EC). The aim of this study was to assess the relationship between the expression of TGF-beta cascade components, including TGF-beta receptor type I (TGF beta RI) and type II (TGF beta RII), SMAD2, SMAD3, SMAD4, and clinicopathological features--tumor grade, FIGO classification, and depth of myometrial invasion--of type I (endometrioid-type) ECs to give some insight into the role of TGF-beta cascade components in endometrial tumorigenesis.', 'The expression of TGF beta RI, TGF beta RII, SMAD2, SMAD3, and SMAD4 was evaluated both at the mRNA and protein level using reverse transcription polymerase chain reaction (RT-PCR) and ELISA, respectively.', 'Infiltrating endometrial carcinomas (less and more than half of the myometrial wall thickness) express significantly higher TGF beta RII protein level compared with non-infiltrating tumors (P = 0.04 and P = 0.01, respectively). Decreased level of SMAD2 and SMAD4 mRNAs was observed in the uterine tumors infiltrating less and more than half of the myometrial wall (P = 0.03 and P = 0.02, respectively) compared with noninfiltrating ECs. Significantly higher SMAD4 protein level in the cytoplasmic fraction of ECs was found when tumor grade and depth of myometrial invasion were considered (P < 0.05). Generally, tumor progression was associated with a decreased number of cases characterized by the presence of SMADs in the nuclear fraction only.",
            "output": [
                "Is tGF-beta signaling disrupted in endometrioid-type endometrial carcinomas?"
            ]
        },
        {
            "id": "task847-1f21032756ee4ed8adab273fe77296ee",
            "input": "Adenosine diphosphate (ADP) is involved in shear-induced platelet activation, which may be important for platelet responses to stress. We therefore tested the hypothesis that ADP receptor antagonism by clopidogrel treatment would attenuate exercise-induced platelet activation.', 'Fifteen healthy volunteers performed exhaustive exercise without and with clopidogrel pretreatment (75 mg/day; 7 days) in a randomised crossover study. Filtragometry readings (reflecting platelet aggregability in vivo) and 11-dehydro-thromboxane B(2) (TxM) in plasma were determined before and after exercise. Platelet and leukocyte activity, platelet-platelet (PPA), and platelet-leukocyte aggregates (PLAs) in vivo and their responsiveness to agonist stimulation in vitro were assessed by flow cytometry. Clopidogrel treatment inhibited ADP-induced platelet P-selectin expression by 72% (54-85%). Exercise increased platelet aggregation (filtragometry and PPAs), elevated plasma TxM, increased single platelet P-selectin expression, elevated circulating PLAs, and enhanced ADP and thrombin-stimulated P-selectin expression. Clopidogrel prolonged filtragometry readings and attenuated agonist stimulated P-selectin expression at rest, but did not influence TxM in plasma or urine or attenuate platelet or leukocyte responses to exercise. Clopidogrel treatment did not influence plasma CD40L (ligand) at rest or after exercise.",
            "output": [
                "Are prothrombotic responses to exercise little influenced by clopidogrel treatment?"
            ]
        },
        {
            "id": "task847-ea0079ec1d714eb4bbbbc0c3377ff4d5",
            "input": "N-acetylcysteine (NAC) may modulate the initial phase (less than 2 h) of liver warm ischaemia-reperfusion (IR) injury but its effect on the late phase remains unclear. The present study investigated the role of NAC during the early and late phases in a rabbit lobar IR model.', 'Liver ischaemia was induced by inflow occlusion to the median and left liver lobes for 60 min, followed by 7 h of reperfusion. In the NAC group (n = 6), NAC was administered intravenously at 150 mg per kg over the 15 min before reperfusion and maintained at 10 mg per kg per h during reperfusion. In the IR group (n = 6), 20 ml 5 per cent dextrose was infused over the 15 min before reperfusion and continued at a rate of 10 ml/h. Animals in a sham operation group (n = 6) underwent laparotomy but no liver ischaemia. All animals were killed at the end of the experiment.', 'Intracellular tissue oxygenation was improved after the second hour of reperfusion in animals treated with NAC compared with that in the IR group (P = 0.023). Hepatic microcirculation improved after 5 h of reperfusion (P = 0.036) and liver injury was reduced after 5 h, as indicated by alanine aminotransferase activity (P = 0.007) and indocyanine green clearance (uptake, P = 0.001; excretion, P = 0.032).",
            "output": [
                "Does continuous infusion of N-acetylcysteine reduce liver warm ischaemia-reperfusion injury?"
            ]
        },
        {
            "id": "task847-957246b1794845f398a7b8830aedf5eb",
            "input": "Considerable variation exists in the protocols used to induce hyperresponsiveness in murine models of allergic sensitisation. We examined the effect of varying the number of antigen exposures at challenge on the development of methacholine responsiveness in systemically sensitised mice.', 'BALB/c mice were sensitised with ovalbumin (OVA), challenged with 1, 3 or 6 OVA aerosols. Lung function was measured using low frequency forced oscillations and partitioned into components representing the airways (Raw) and lung parenchyma (tissue damping (G) and tissue elastance (H)). Responsiveness to inhaled methacholine (MCh), inflammatory cell profile and circulating IgE were assessed 24 and 48 hours after challenge. The threshold dose of MCh required to elicit a detectable response (sensitivity) and response to 30 mg x mL(-1) (maximal response) were determined for each compartment.', 'Sensitivity; All three OVA protocols resulted in an increased sensitivity to MCh in Raw but not in G or H. These responses where present at 24 and 48 hrs, except 1 OVA aerosol in which changes had resolved by 48 hrs. Maximal response; 1 OVA aerosol increased maximal responses in Raw, G and H at 24 hrs, which was gone by 48 hrs. Three OVA aerosols increased responses in H at 48 hrs only. Six OVA challenges caused increases in Raw, G and H at both 24 and 48 hrs. Eosinophils increased with increasing antigen challenges. IgE was elevated by OVA sensitisation but not boosted by OVA aerosol challenge.",
            "output": [
                "Is the pattern of methacholine responsiveness in mice dependent on antigen challenge dose?"
            ]
        },
        {
            "id": "task847-ce0f9a9f83e04ece882c932268c259e9",
            "input": "The Mycoplasma hominis vaa gene encodes a highly variable, surface antigen involved in the adhesion to host cells. We have analysed the structure of the vaa locus to elucidate the genetic basis for variation of vaa.', \"Mapping of vaa on existing physical maps of five M. hominis isolates by pulsed field gel electrophoresis revealed that vaa is located in a genomic region containing the majority of other characterized membrane protein genes of M. hominis. Sequencing of an 11 kb region containing the vaa locus of M. hominis isolate 132 showed the presence of conserved housekeeping genes at the borders of the region, uvrA upstream and the hitABL operon downstream to vaa. Analysis of 20 M. hominis isolates revealed that the vaa upstream region was conserved whereas the downstream region was highly variable. In isolate 132 this region contained an open reading frame (ORF) encoding a putative 160 kDa membrane protein. Homologous ORFs were present in half of the isolates, whereas this ORF, termed vmp (variable membrane protein), was deleted from the locus in the remaining isolates. Compellingly, the conserved upstream region and variable downstream region of vaa correlates with the genetic structure of vaa itself which consists of a conserved 5' end and a variable 3' end containing a variable number of exchangeable sequence cassettes.",
            "output": [
                "Does the vaa locus of Mycoplasma hominis contain a divergent genetic islet encoding a putative membrane protein?"
            ]
        },
        {
            "id": "task847-581482fc58ff47f6b8d87293a7859d80",
            "input": "Donor-specific transfusion (DST) and a brief course of anti-CD154 monoclonal antibody (mAb) induces permanent islet and prolonged skin allograft survival in mice. Induction of skin allograft survival requires the presence of CD4 cells and deletion of alloreactive CD8 cells. The specific roles of CD4 and CD4CD25 cells and the mechanism(s) by which they act are not fully understood.', 'We used skin and islet allografts, a CD8 T cell receptor (TCR) transgenic model system, and in vivo depleting antibodies to analyze the role of CD4 cell subsets in regulating allograft survival in mice treated with DST and anti-CD154 mAb.', 'Deletion of CD4 or CD25 cells during costimulation blockade induced rapid rejection of skin but only minimally shortened islet allograft survival. Deletion of CD4 or CD25 cells had no effect upon survival of healed-in islet allografts, and CD25 cell deletion had no effect upon healed-in skin allograft survival. In the TCR transgenic model, DST plus anti-CD154 mAb treatment deleted alloreactive CD8 T cells, and anti-CD4 mAb treatment prevented that deletion. In contrast, injection of anti-CD25 mAb did not prevent alloreactive CD8 T cell deletion.",
            "output": [
                "Is regulation of skin and islet allograft survival in mice treated with costimulation blockade mediated by different CD4+ cell subsets and different mechanisms?"
            ]
        },
        {
            "id": "task847-b334a2f6b8234260926c5108d70a5074",
            "input": "Postoperative day-case patients are usually allowed to recover from anaesthesia in a postanaesthesia care unit (PACU) before transfer back to the day surgical unit (DSU). Bypassing the PACU can decrease recovery time after day surgery. Cost savings may result from a reduced nursing workload associated with the decreased recovery time. This study was designed to evaluate the effects of bypassing the PACU on patient recovery time and nursing workload and costs.', 'Two hundred and seven consenting outpatients undergoing day surgery procedures were enrolled. Anaesthesia was induced and maintained with a standardized technique and the electroencephalographic bispectral index was monitored and maintained at 40-60 during anaesthetic maintenance. At the end of surgery, patients were randomly assigned to either a routine or fast-tracking (FT) group. Patients in the FT group were transferred from the operating room to the DSU (i.e. bypassing the PACU) if they achieved the FT criteria. All other patients were transferred to the PACU and then to the DSU. Nursing workload was evaluated using a patient care hour chart based on the type and frequency of nursing interventions in the PACU and DSU. A cost associated with the nursing workload was calculated.', 'The overall time from end of anaesthesia to discharge home was significantly decreased in the fast-tracking group. However, overall patient care hours and costs were similar in the two recovery groups.",
            "output": [
                "Does fast-tracking ( bypassing the PACU ) reduce nursing workload after ambulatory surgery?"
            ]
        },
        {
            "id": "task847-c1d129fb49a947be8cb8fac02e9117b5",
            "input": "The calcium-channel blocking effect of magnesium might have protective effects in patients undergoing cardiopulmonary bypass surgery. We assessed the effects of magnesium on hearts undergoing coronary artery bypass surgery with intermittent warm blood hyperkalemic cardioplegia in the antegrade fashion.', 'Twenty patients undergoing coronary bypass surgery were randomly divided into two groups, a control group who received intermittent antegrade warm blood hyperkalemic cardioplegia for myocardial protection, and a study group who received the same solution with the addition of magnesium to the cardioplegia. Extracellular substrates (creatinine phosphokinase, creatinine phosphokinase-MB group, lactate dehydrogenase, c-reactive protein, and cardiac troponin I were measured preoperatively and postoperatively.', 'There were significant differences in the post-operative concentrations of creatinine phosphokinase, creatinine phosphokinase-MB group, c-reactive protein, and lactate dehydrogenase after cardiopulmonary bypass (P<0.001) in the study group compared with the control subjects. Cardiac troponin I levels were also significantly lower in the study group after cardiopulmonary bypass (P<0.005).",
            "output": [
                "Does magnesium decrease cardiac injury in patients undergoing coronary artery bypass surgery?"
            ]
        },
        {
            "id": "task847-13254f29f7f44f9387fd7105c5c06636",
            "input": "Uremic toxins have been shown to promote glomerular hypertrophy. The present study was performed to elucidate the relation between uremic toxins and tubulointerstitial changes.', 'Sixty male Sprague-Dawley rats underwent 2/3 nephrectomy (Nx; n = 30) and 4/5 Nx (n = 30). Experiments were initiated 2 weeks after surgery, and were performed over an 8-week period. Half of each group (Nx-A) was administered 1 g/day of an oral carbonaceous adsorbent, AST-120, with pair-feeding, and the other half (Nx-C) served as controls. All rats were sacrificed at week 8 after a clearance study.', 'The shortest diameter of proximal tubules (PTD) and interstitial fibrosis area (IFA) at week 8 in 2/3 Nx-A rats was significantly decreased compared to that in 2/3 Nx-C rats (similar body weights, systolic blood pressures, glomerular filtration rates, and urinary protein excretion levels). The values of PTD and IFA, glomerular filtration rate and urinary protein excretion level at week 8 in 4/5 Nx-A rats were significantly decreased compared to those in 4/5 Nx-C rats (similar body weights and systolic blood pressures).",
            "output": [
                "Do uremic toxins adsorbed by AST-120 promote tubular hypertrophy and interstitial fibrosis in nephrectomized rats?"
            ]
        },
        {
            "id": "task847-437c23979a5f4173bc5a1359b929e72b",
            "input": "There is controversy as to whether migraine is associated with white matter abnormalities (WMAs) on magnetic resonance images. These abnormalities may be important as a risk factor for future stroke. Further, it is controversial whether any increased risk of WMAs is attributable to comorbidities such as vascular disease.', 'A meta-analysis of published case-control studies was undertaken to address the relationship between migraine and magnetic resonance imaging WMAs. Seven studies were identified. Data from studies reporting the incidence of magnetic resonance imaging WMAs in those with migraine and appropriate control populations were used to calculate odds ratios for WMAs in migraine for each study. A stratified meta-analysis was performed using studies that did and did not exclude subjects with disease comorbidities.', 'The summary odds ratio shows that those with migraine are at increased risk for WMAs (odds ratio, 3.9 [95% confidence interval, 2.26-6.72]). The risk does not differ between studies that included subjects with comorbidities and those that did not.",
            "output": [
                "Is migraine associated with magnetic resonance imaging white matter abnormalities : a meta-analysis?"
            ]
        },
        {
            "id": "task847-694e41482f5f424c942429d9b831a1fd",
            "input": "This study assessed modulation of hypoxic pulmonary vasoconstriction (HPV) in isolated perfused rat lungs during sepsis induced by cecal ligation and perforation (CLP) at different times and its relationship to nitric oxide synthases (NOS).', 'Prospective controlled trial in a university research laboratory.', '102 male Sprague-Dawley rats.', \"Groups 1-3 received sham laparotomy 6 h before lung isolation: group 1, only laparotomy; group 2, concurrently L- N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg); group 3, concurrently N(Omega)-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Groups 4-6 received CLP 6 h before lung isolation: group 4, only CLP; group 5, concurrently L-NIL; group 6, concurrently L-NAME. The same experiments were carried out with sham and CLP treatment for 24 h (groups 7-12). Exhaled NO from rats' lungs was measured after anesthesia and tracheostomy. After the pulmonary circuit was isolated and perfused, angiotensin II (0.1 microg) was injected into the inflow tract. The lungs were ventilated with the hypoxic mixture (HPV, 3% O2) for 10 min and then again with the normoxic mixture (21% O2) for an equal period. Changes in perfusion pressure were measured. Endothelial (eNOS) and inducible NOS (iNOS) expression of the lungs was determined.\", 'Treatment with L-NAME but not L-NIL increased HPV in sham lungs. HPV was unaltered after CLP 6 h and decreased after CLP 24 h compared to sham. In CLP animals eNOS protein expression was reduced whereas iNOS expression was increased compared to sham animals. Exhaled NO, reflecting NOS activity was twice as high in the CLP 24 h group than in the CLP 6 h group.",
            "output": [
                "Is modulation of hypoxic pulmonary vasoconstriction time and nitric oxide dependent in a peritonitis model of sepsis?"
            ]
        },
        {
            "id": "task847-1a46fd4fbf2d47bdb3caedaea415b221",
            "input": "Scutellaria barbata D.Don has been applied to treat cancers, inflammation and urinary disease. However, its antitumor mechanism still remains unclear.', 'With methylene chloride fraction of Herba Scutellariae barbatae (MCSB), apoptosis-related experiments were carried out on human U937 leukemia cells by (a) 2,3-bis[2-4-nitro-5-sulphophenyl]2H-tetrazolium-5-carboxanilide (XTT) assay for cytotoxicity; (b) terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay for morphological changes; (c) cell cycle analysis; (d) Western blot analysis of poly(ADP-ribose) polymerase (PARP), caspase-8, caspase-9, caspase-3 and Bax, Bcl-2 and cytochrome c expressions for apoptosis signaling pathway.', 'MCSB inhibited the proliferation of human U937 leukemia cells in a dose-dependent manner (IC50 = approximately 10 microg/ml). MCSB dose-dependently increased the sub-G1 DNA contents by cell cycle analysis. DNA fragments indicating induction of apoptosis were observed in MCSB-treated U937 cells by TUNEL assay. Caspase-9 and caspase-3 were activated while caspase-8 was intact by MCSB. Similarly, MCSB effectively cleaved PARP, increased the ratio of Bax/Bcl-2 and released the cytochrome c from mitochondria during apoptosis in U937 cells.",
            "output": [
                "Does methylene chloride fraction of Scutellaria barbata induce apoptosis in human U937 leukemia cells via the mitochondrial signaling pathway?"
            ]
        },
        {
            "id": "task847-246cb0bb1be449c7b160142e4b9ed4c8",
            "input": "Tolerance to ischemic brain injury is induced by several preconditioning stimuli, including lipopolysaccharide (LPS). A small dose of LPS given systemically confers ischemic protection in the brain, a process that appears to involve activation of an inflammatory response before ischemia. We postulated that LPS preconditioning modulates the cellular inflammatory response after cerebral ischemia, resulting in neuroprotection.', 'Mice were treated with LPS (0.2 mg/kg) 48 hours before ischemia induced by transient middle cerebral artery occlusion (MCAO). The infarct was measured by 2,3,5-triphenyltetrazolium chloride staining. Microglia/macrophage responses after MCAO were assessed by immunofluorescence and flow cytometry. The effect of MCAO on white blood cells in the brain and peripheral circulation was measured by flow cytometry 48 hours after MCAO.', 'LPS preconditioning induced significant neuroprotection against MCAO. Administration of low-dose LPS before MCAO prevented the cellular inflammatory response in the brain and blood. Specifically, LPS preconditioning suppressed neutrophil infiltration into the brain and microglia/macrophage activation in the ischemic hemisphere, which was paralleled by suppressed monocyte activation in the peripheral blood.",
            "output": [
                "Does endotoxin preconditioning prevent cellular inflammatory response during ischemic neuroprotection in mice?"
            ]
        },
        {
            "id": "task847-db2d8f4aca9646c5bc12c6c23ea9a183",
            "input": "Early stage patients with Parkinson's disease (PD) show cognitive impairment in frontal lobe functions and memory tests. Hippocampal atrophy is seen in medicated patients with advanced PD.\", 'To examine whether prefrontal or hippocampal atrophy are already present in early stage PD, and whether such atrophy is associated with cognitive impairment.', 'Twenty non-medicated, non-demented patients with early stage PD and 22 neurologically healthy age matched controls were studied. All subjects underwent magnetic resonance imaging to study hippocampal and prefrontal atrophy. Atrophy was evaluated by a neuroradiologist using a five point scale. In addition, the patients underwent a neuropsychological test battery sensitive to frontal lobe functions and memory.', 'Patients with PD had atrophy in the right and the left prefrontal cortex. In the right hippocampus, the mean atrophy score was 1.15 in PD and 0.45 in controls. Corresponding figures for the left hippocampus were 1.05 for PD and 0.64 for controls. In PD, the left hippocampus atrophy correlated with verbal memory and prefrontal atrophy correlated with impaired performance in a test measuring vigilance.",
            "output": [
                "Is hippocampal and prefrontal atrophy in patients with early non-demented Parkinson 's disease related to cognitive impairment?"
            ]
        },
        {
            "id": "task847-fa920e72bc164fdc9e886f4279af9058",
            "input": "Nitric oxide (NO), an important mediator of the inflammatory response, is involved in several reproductive processes including pregnancy and labor. Uterus, placenta and fetal membranes are significant sources of NO. Presently, there is no information on factors regulating NO production by fetal membranes.', 'Human fetal membranes at term gestation were cultured for 24 hr in the presence of oxytocin. The concentrations of NO metabolites nitrites in culture medium were determined by the Griess reaction. The presence of inducible nitric oxide synthase (iNOS) was determined by reverse transcriptase-polymerase chain reaction and Western blot.', 'Oxytocin increased nitrite release by fetal membranes. Messenger ribonucleic acid iNOS expression was also enhanced by oxytocin. These effects were more marked in tissues obtained after labor than before labor.",
            "output": [
                "Does oxytocin modulate nitric oxide generation by human fetal membranes at term pregnancy?"
            ]
        },
        {
            "id": "task847-1240d28e411f4375b9a6af1f81397c5b",
            "input": "Cardiac allograft vasculopathy (CAV) is initiated by allograft endothelial injury. We hypothesized that a major mechanism by which cytomegalovirus (CMV) could contribute to CAV is by dysregulation of the endothelial vasomotor response.', 'Coronary endothelial vasomotor function was determined in 183 consecutive patients (24+/-33 months after transplantation), and was correlated with recipient and donor CMV serological status before transplantation and with documented CMV infection episodes (CMVpp65Ag+). Serial endothelial function measurements were performed in a subgroup of 53 transplant recipients (1 month and 12 months after transplantation). The composite endpoint of cardiovascular related events and death during a follow-up of 66+/-41 months was analyzed based on the CMV serological status before transplantation.', 'The medium event-free time for CMV-negative recipients of CMV-positive hearts was 8.1 years compared with 13.3 years for the other groups (P<0.05). Distal epicardial but not microvascular endothelial function was significantly impaired in CMV seronegative recipients of seropositive donor hearts (n=48) compared with all other groups (P<0.01 versus seronegative recipient/seronegative donor; P<0.05 versus seropositive recipient/seronegative donor; P<0.05 versus seropositive recipient/seropositive donor). Distal epicardial endothelial dysfunction was more pronounced in heart transplant recipients with a history of documented CMV infection compared with patients without any documented CMV infection (P<0.01). In a longitudinal subgroup analysis, distal epicardial and microcirculatory endothelial vasomotor response deteriorated significantly in recipients with documented CMV infection (P<0.05 versus baseline) but not in patients without previous CMV infection.",
            "output": [
                "Is cytomegalovirus infection in heart transplant recipients associated with impaired endothelial function?"
            ]
        },
        {
            "id": "task847-199f6161dc384823bbbd108d5bd06260",
            "input": "Nonviral vectors based on polyethylenimine (PEI) usually contain an excess of PEI that is not complexed to DNA. Since unbound PEI contributes to cellular and systemic toxicity, purification of polyplexes from unbound PEI is desirable.', 'Size exclusion chromatography (SEC) was used to purify PEI polyplexes of free PEI. Transfection properties of purified polyplexes and the effect of free PEI on gene delivery were studied in vitro and in vivo after systemic application into mice.', 'SEC did not change the size and zeta-potential of polyplexes. Independent of the amount of PEI used for complex formation, purified PEI polyplexes had the same final PEI nitrogen/DNA phosphate ratio of 2.5. Notably, purified PEI polyplexes demonstrated low cellular and systemic toxicity. High transfection efficiency was achieved with purified polyplexes at high DNA concentrations (8-15 microg/ml). At low DNA concentrations (2-4 microg/ml) gene transfer with purified particles was less efficient than with polyplexes containing free PEI both in vitro and in vivo. Mechanistic studies showed that free PEI partly blocked cellular association of DNA complexes but was essential for the following intracellular gene delivery. Adding free PEI to cells treated with purified particles with a delay of up to 4 h resulted in significantly enhanced transfection efficiency compared with non-purified particles or purified particles without free PEI.",
            "output": [
                "Does purification of polyethylenimine polyplexes highlight the role of free polycations in gene transfer?"
            ]
        },
        {
            "id": "task847-f747c3ac9bb5448283ca9892b08179f6",
            "input": "Histologic evidence of the comparative neurotoxicity of lidocaine, mepivacaine, and prilocaine is incomplete. We compared the intrathecal neurotoxicity in rats among these 3 drugs based on morphologic and neurofunctional findings.', 'Rats (n=169) randomly received 0.12 microL/g of 0%, 2%, 5%, 7.5%, 10%, or 20% lidocaine, mepivacaine, or prilocaine or 25% glucose dissolved in distilled water via a chronically implanted intrathecal catheter. The effect of the agents on neurofunction was evaluated by movement of the hind limb (behavior test) and by sensory threshold (paw-stimulation test). The L1 spinal cord, the posterior and anterior roots, and the cauda equina were removed en bloc 5 days later and examined by light and electron microscopy.', 'A significant decrease in sensory threshold or irreversible hind-limb limitation was observed only in rats receiving 20% lidocaine. Morphologic abnormalities characterized by axonal degeneration were observed in rats receiving > or =7.5% lidocaine, 20% mepivacaine, and 20% prilocaine, at the posterior white matter and the proximal portion of the posterior root just at the entrance into the spinal cord. The incidence of lesions was significantly higher in rats receiving lidocaine than mepivacaine and prilocaine.",
            "output": [
                "Are intrathecal mepivacaine and prilocaine less neurotoxic than lidocaine in a rat intrathecal model?"
            ]
        },
        {
            "id": "task847-dc767db29cf74ec28ac1b7f803249d6f",
            "input": "LADA is thought to result from the chronic autoimmune destruction of the insulin-producing pancreatic beta cells. In addition to antidiabetic effects, the newly developed insulin sensitizer-thiazolidinediones have the potential to increase the insulin content of islet cells by downregulating local inflammation and autoimmune response. Therefore, we hypothesized that LADA patients might benefit from thiazolidinediones treatment.', 'LADA patients, with a fasting C-peptide (FCP) of 0.3 nmol/L or more, were enrolled and randomly assigned to receive subcutaneous insulin alone (insulin group, n = 12) or rosiglitazone plus insulin (insulin + RSG group, n = 11) to compare the impacts on islet beta cell function. Plasma glucose, HbA 1c, fasting C-peptide (FCP) and C-peptide after 2 h 75-g glucose load (PCP) were determined every 6 months. GAD-Ab and C-peptide were measured with radioimmune assays. Islet beta cell function was evaluated by PCP and DeltaCP(DeltaCP = PCP-FCP).', \"All of the 23 patients have been followed up for 6 months, 17 cases for 12 months and 14 for 18 months. (1) During 6 months' follow-up, there were no significant changes for DeltaCP and PCP levels in both groups. (2) PCP and DeltaCP levels in insulin + RSG group patients stayed steady during the 12 months' observation (P = 0.161 for both PCP and DeltaCP), while in the insulin alone group, both FCP (P = 0.021) and PCP (P = 0.028) levels decreased significantly. Furthermore, PCP (P = 0.004) and DeltaCP(P = 0.015) differences between 12th month and baseline were higher in insulin + RSG group than those in the insulin group. (3) When observed up to 18 months, PCP and DeltaCP levels in insulin + RSG group patients still stayed steady, while PCP and DeltaCP levels decreased more in the insulin alone group.",
            "output": [
                "Does rosiglitazone combined with insulin preserve islet beta cell function in adult-onset latent autoimmune diabetes ( LADA )?"
            ]
        },
        {
            "id": "task847-70542de8fffb4d388d56d699a09bac30",
            "input": "The purpose of this study was to determine whether four types of professionalism deficiencies in medical students identified during a first-year course on doctor-patient relationships might predict poor performance in third-year clerkships.', 'Preceptors identified students who had deficiencies in interviewing patients: extreme shyness, poor process skills, paternalism, or a negative attitude toward interviewing. Deficient students were matched by academic ability to a control group. Performance on third-year clerkships was compared.', 'Students with paternalistic behavior or negative attitudes had significantly lower third-year grades.",
            "output": [
                "Do professionalism deficiencies in a first-quarter doctor-patient relationship course predict poor clinical performance in medical school?"
            ]
        },
        {
            "id": "task847-5c869dc2158b496c8debe62579722093",
            "input": "To analyze the KRT6A gene mutation and mutating patterns in a sporadic Chinese patient with Pachyonychia congenita (PC)-1 so as to provide a basis for gene diagnosis and genetic counseling of this disorder.', 'Genomic DNA was extracted from whole blood by standard methods from a female patient with PC-1 and her parents, and from 50 normal, unrelated individuals. Primers for specific amplification of the structural KRT6A gene without co amplification of homologous genes were designed and synthesized. All exons of the gene and their flanking intronic sequences were amplified using polymerase chain reaction (PCR) and subjected to automatic DNA sequencing. The mutation was confirmed by Mbo I restriction digestion of the KRT6A-specific PCR products.', \"Direct sequencing of the PCR products revealed a novel heterozygous missense mutation, I462S in the KRT6A gene, which resulted from T to G transversion at nucleotide 1385 (1385T > G) in exon 7 was detected in the patient. This mutation would result in the substitution of Isoleucine by Serine at codon 462 (I462S) located in the end 2B domain of keratin 6A. No such mutation was found in the patient's parents by sequencing of PCR products and this mutation was confirmed in the patient and excluded from both parents and 50 normal, unrelated controls by restriction analysis of PCR fragments using Mbo I enzyme.",
            "output": [
                "Is [ A de nono I462S mutation in the KRT6A gene associated with pachyonychia congenita type I ]?"
            ]
        },
        {
            "id": "task847-d9ff28e68a07490aa3101f569a78fe40",
            "input": "Serum prostate-specific antigen (PSA) level is a widely used serum marker for diagnosis and management of prostate cancer. Although not well-defined, liver appears to be the most likely site of PSA metabolism. However, general anaesthesia usually changes hepatic blood flow, therefore it may affect the metabolism of PSA. In this study we investigated the affect of general anaesthesia on the serum total PSA, free PSA and free to total PSA levels.', '30 male patients who were hospitalised in the internal medicine clinic (non-surgery group) and 30 male patients who would undergo operation under general anaesthesia (15 for cholecystectomy and 15 for inguinal hernia repair) enrolled into the study. PSA measurement was done on the day of the hospitalisation (which was also the day of operation for surgery group), on the 24th hour following the first measurement and on the 21st day. Anaesthesia was standardized for all patients.', 'There was no statistically significant difference in serum total PSA (p >0.05), free PSA levels (p >0.05) and free to total PSA ratio (p >0.05) between the surgery and non-surgery groups. There were statistically significant decreases in the 24th hour total PSA levels (13.8% in surgery group, p <0.05, and 13.1% in non-surgery group, p <0.05) and in the free PSA levels (4.0% in surgery group, p <0.05, and 8.2% in non-surgery group, p <0.05). There was no statistically significant difference in the free to total PSA ratios (p >0.05 and p >0.05, respectively).",
            "output": [
                "Does general anesthesia affect the serum complexed and free prostate specific antigen levels?"
            ]
        },
        {
            "id": "task847-3d82b282266946f6ac27baf43f0a2d22",
            "input": "The hypothesis that intrapericardial (ip.) ibutilide administration would terminate pacing-induced sustained atrial fibrillation (AF) and ibutilide distribution were tested.', 'Sustained (> or =24 hours) AF was induced by 59 +/- 20 day rapid atrial pacing in 19 dogs. After sustained AF was present, the atrial pacemaker was turned off and 9 open chest dogs received 0.015 mg/kg ibutilide (37 degrees C) in 30 ml saline into the pericardial sac. Ten control dogs received 30 ml saline (37 degrees C) ip. QT intervals, right ventricular monophasic action potential duration at 90% of repolarization (RV-MAPD(90)), AF mean cycle length (AFCL(m)), systolic- and diastolic intraarterial blood pressures, intrapericardial-, right atrial- and ventricular pressures, cardiac output and ibutilide concentrations were measured. If AF persisted after the 1st drug infusion, dual site rapid atrial pacing (DRAP) simultaneously from the high right atrium and coronary sinus was performed to terminate AF. If it was ineffective, a 2nd ip. drug infusion in the same fashion as the 1st one, was attempted. There was no significant difference in AF termination [5/9 (56%) in ibutilide treated and 3/10 (30%) in control dogs] between the two groups. DRAP never terminated AF. The AF duration did not differ between the two groups. Compared with control, ibutilide treatment prolonged significantly AFCL(m) (p < 0.001) and non-significantly QT, RV-MAPD(90). No significant difference was found in systolic and diastolic blood pressure and cardiac output between the two groups. The two orders of magnitude greater ibutilide concentration in the pericardial fluid than that in the femoral vein decreased rapidly over time, drug concentration was greatest in the atria, smaller in the ventricular myocardium, with a trend decreasing from the epi- to endocardium.",
            "output": [
                "Does intrapericardial ibutilide administration fail to terminate pacing-induced sustained atrial fibrillation in dogs?"
            ]
        },
        {
            "id": "task847-730c246a96254e4ea84ec666bb3eb42e",
            "input": "Nutritional depletion has been correlated with low plasma and mucosal glutamine concentrations and with increased intestinal permeability. Since nutritional depletion often is associated with (chronic) inflammatory stress, this study was designed to establish the influence of depletion and inflammation on glutamine concentrations and gut barrier function.', 'Anthropometric parameters were calculated from 26 patients who required artificial nutrition. Glutamine concentrations in plasma and gut mucosa, gut permeability and mucosal morphology were assessed. For determination of the degree of inflammation erythrocyte sedimentation rates and (pre)albumin concentrations were measured. On the basis of these parameters patients were divided into two groups having significant inflammatory stress or not. Similarly, a depleted and a non-depleted group was formed based on percentage ideal body weight, fat-free mass index (FFMI) and percentage weight loss. Glutamine concentrations, gut permeability and villus morphology were compared between the groups.', 'The presence of inflammatory activity had significant negative effects on glutamine concentrations in contrast to the presence or absence of nutritional depletion. Similarly, intestinal permeability increased during active inflammation but not in depleted patients. FFMI but not inflammation was related to villus height.",
            "output": [
                "Does inflammation rather than nutritional depletion determine glutamine concentrations and intestinal permeability?"
            ]
        },
        {
            "id": "task847-e6af8a340a0140279dd8f8398e5a8c37",
            "input": "Allicin, the active substance of fresh crushed garlic has different biological activities and was implicated as an anti-inflammatory agent. Epithelial cells have an important role in intestinal inflammation. The aim of this study was to assess the immunomodulatory effect of allicin on intestinal epithelial cells.', 'The spontaneous and TNF-alpha-stimulated secretion of IL-1beta, IL-8, IP-10 and MIG from HT-29 and Caco-2 cells was tested with, or without pretreatment with allicin. Cytokine secretion was assessed using ELISA and expression of mRNA was determined by an RNA protection assay.', 'Allicin markedly inhibited the spontaneous and TNF-alpha -induced secretion of IL-1beta, IL-8, IP-10 and MIG from the two different cell lines in a dose-dependent manner and suppressed the expression of IL-8 and IL-1beta mRNA levels. In addition, allicin suppressed the degradation of IkappaB. No effect on cell viability was noted.",
            "output": [
                "Does allicin inhibit spontaneous and TNF-alpha induced secretion of proinflammatory cytokines and chemokines from intestinal epithelial cells?"
            ]
        },
        {
            "id": "task847-fa74ab73b22f4eeb8237ad15f1d8f76a",
            "input": "Interferon alpha2a (IFNalpha2a) mediates important antiviral, antiproliferative and immunomodulatory responses and is employed in the treatment of human diseases, including chronic myelogenous leukemia. Here, we report the IFNalpha2a-dependent expression profiles of three malignant cell lines derived from liver, lymphocytes and muscle.', 'The experiments were performed in the presence of cycloheximide, thus our results exclusively reflect direct transcriptional modulation. The short exposure time i.e. 5 hours evidences only the early events, excluding the effects of complex phenotypic changes on the expression.', \"Our findings indicate that IFNalpha2a rapidly up-regulates the expression of STAT1, STAT2 and ISGF3G genes. This activity should result in the amplification of the cellular response to the cytokine. Moreover, IFNalpha2a directly modulates the expression of: (i) important transcriptional factors, e.g. IRF1 and IRF7 which control pivotal cellular events, and (ii) enzymes involved in the IFNalpha2a-dependent antiviral and apoptotic response. Interestingly, we showed that the cytokine induces transcriptional expression of Sj\u00f6gren's syndrome antigen A1, a protein involved in several autoimmune diseases.",
            "output": [
                "Do genes transcriptionally modulated by interferon alpha2a correlate with the cytokine activity?"
            ]
        },
        {
            "id": "task847-0a6dd8620e954101b3fb7109bfa07f17",
            "input": "The aim of this study was to evaluate the clinical value of markers of bone remodeling in assessment of rate of bone loss in patients with multiple sclerosis (MS) long term treated with low dose glucocorticoids.', 'The study involved 70 patients with MS. Motor function of the patients was evaluated using the Kurtzke Expanded Disability Status Scale (KEDSS). Bone mineral density (BMD) was determined at the lumbar spine and proximal femur at baseline and after 1.8 +/- 0.8 years. Bone remodeling was assessed using circulating concentrations of type 1 collagen cross-linked C-telopeptide (beta CTX), aminoterminal propeptide of type I procollagen, and N-MID osteocalcin (OC). A control group of 140 age-matched healthy subjects was used to compare bone-turnover markers.', 'The plasma CTX concentration was the most significant parameter of bone remodeling which correlated with the rate of bone loss and with the KEDSS. The rate of bone loss at the proximal femur was not significantly different between tertiles of plasma OC concentrations.",
            "output": [
                "Do markers of bone remodeling predict rate of bone loss in multiple sclerosis patients treated with low dose glucocorticoids?"
            ]
        },
        {
            "id": "task847-fb1b923ebe9640048c120b79032c1bc1",
            "input": "Recent findings suggest that adenosine is involved in the neural and behavioral effects of ethanol (EtOH). Studies in neural cell culture show that EtOH, via activation of adenosine A2 receptors, triggers cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling and CRE (cAMP regulatory element)-mediated gene expression and that this effect is blocked by inhibiting G-protein betagamma subunits. Recently, we reported that expression of a betagamma inhibitor in the nucleus accumbens (NAc) reduces EtOH drinking in rats. The NAc expresses high levels of the adenosine A2A receptor in GABAergic medium spiny neurons. If the reinforcing effects of EtOH are mediated through an A2 activation of cAMP/PKA signaling via betagamma, then A2 receptor blockade should attenuate EtOH consumption. Here we tested this hypothesis. Because adenosine A2 and dopamine D2 receptors are coexpressed in neurons of the NAc, we compared the effects of A2 blockade with those of D2 receptor blockade.', 'Male Long-Evans rats were trained to self-administer 10% EtOH in daily 30-min sessions with an active and an inactive lever. Separate groups of rats were given the D2 antagonist eticlopride (0.005, 0.007, and 0.01 mg/kg), the A2 antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 1, 3, 5, 7, 10, and 20 mg/kg), and the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.125, 0.25, and 0.5 mg/kg) by systemic injection.', 'Eticlopride dose-dependently reduced EtOH drinking. DMPX showed a bimodal effect: 10 and 20 mg/kg decreased, but 1 mg/kg increased, EtOH consumption. DPCPX was without effect.",
            "output": [
                "Is ethanol operant self-administration in rats regulated by adenosine A2 receptors?"
            ]
        },
        {
            "id": "task847-7515334f7acf405b9a8097d45eb7040d",
            "input": "Neuropeptide Y (NPY) is a 36-amino acid neuromodulator that is expressed throughout the central nervous system. Recent genetic and pharmacological evidence suggests that the NPY Y1 receptor modulates ethanol intake. To further characterize the role of the Y1 receptor, we examined voluntary ethanol consumption by mice after administration of [(-)-2-[1-(3-chloro-5-isopropyloxycarbonylaminophenyl)ethylamino]-6-[2-(5-ethyl-4-methyl-1,3-tiazol-2-yl)ethyl]-4-morpholinopyridine] (compound A), a novel and selective Y1 receptor antagonist (Y1RA) that acts centrally on brain receptors when administered peripherally.', 'C57BL/6J mice were habituated to drinking a 10% (v/v) ethanol solution by using a two-bottle-choice procedure and were then given an intraperitoneal (ip) injection (5 ml/kg) of the Y1RA (0, 25, 50, or 75 mg/kg). In a second study, mice were given intracerebroventricular infusion of the Y1RA (0, 30, or 100 microg). Finally, we determined whether the Y1RA alters open-field locomotor activity, ethanol-induced sedation (3.8 g/kg, ip), or blood ethanol levels.', 'Relative to control treatment, ip injection (50 and 75 mg/kg) and intracerebroventricular infusion (100 microg) of the Y1RA significantly reduced ethanol consumption and food intake without altering water drinking. However, the Y1RA did not alter open-field locomotor activity, ethanol-induced sedation, or blood ethanol levels.",
            "output": [
                "Does peripheral and central administration of a selective neuropeptide Y Y1 receptor antagonist suppress ethanol intake by C57BL/6J mice?"
            ]
        },
        {
            "id": "task847-f8019d32c5234ed6916d1311f8aedc36",
            "input": "To examine the lipid profile in Chinese type 2 diabetic patients and their relationship with anthropometric parameters, glycaemic control and cardiovascular mortality.', 'A consecutive cohort of 562 newly referred patients with type 2 diabetes to a hospital-based diabetes centre were examined in 1996. Subjects treated with lipid lowering drugs at the time of referral were excluded. A total of 517 subjects were followed up over a mean (+/-SD) period of 4.6 +/- 0.9 years. Glycated haemoglobin (HbA1c), fasting insulin and lipid profile and anthropometric parameters were documented at the time of recruitment. Cardiovascular mortality, mainly due to coronary heart disease and stroke, was ascertained using death registry and review of hospital case notes in 2001.', 'Of the 517 subjects (mean age of 54.0 +/- 14.0 years), 42.6% were men. In this cohort, 63.3% of subjects were either overweight (BMI > or = 23 kg/m2) or obese (BMI > or = 25 kg/m2) using Asian criteria. The mean (+/-SD) total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C) and geometric mean (x// antilog SD) of triglycerides (TG) were 5.6 +/- 1.3 mmol/L, 3.6 +/- 1.1 mmol/L, 1.3 +/- 0.3 mmol/L and 1.46x//1.90 mmol/L respectively. TC and LDL-C correlated positively with HbA1c, HDL-C negatively with BMI and WC (waist circumference), while TG positively with HbA1c, BMI, WC and HOMA (insulin resistance estimated using the homeostasis model assessment). During the 4.6 years follow-up period, there were 61 deaths giving a total mortality rate of 11.4%, of which 15 (25%) were because of cardiovascular events. Apart from age and disease duration, logarithm of TG was significantly associated with increased risk of cardiovascular mortality (p = 0.049, relative risk = 2.97, 95% CI 1.00-8.77).",
            "output": [
                "Does triglyceride predict cardiovascular mortality and its relationship with glycaemia and obesity in Chinese type 2 diabetic patients?"
            ]
        },
        {
            "id": "task847-19cd369ef35643fc887c378faa6a355a",
            "input": "Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats.', 'Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections.', 'Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBE-treated group (71.8 +/- 4.5%, 53.3 +/- 0.5%, 67.4 +/- 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 +/- 0.05 g, 1.70 +/- 0.08 g, 1.13 +/- 0.05 g in group 0, 1 and 2 respectively) and caffeine-induced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats.",
            "output": [
                "Does calcium dobesilate attenuate vascular injury and the progression of diabetic retinopathy in streptozotocin-induced diabetic rats?"
            ]
        },
        {
            "id": "task847-40ef2bfe0808457b945a48cfc7f37f61",
            "input": "Intracerebral hemorrhage has no effective treatment. The delayed appearance of edema, apoptosis, and inflammation in perihematomal brain suggests that these events may be targets for therapeutic intervention. To develop successful treatments, we must learn more about the effects of hemorrhage on brain tissue. In this study, we investigated the acute metabolic effects of intrastriatal hemorrhage in rat brain.', 'Lysed blood or saline (50 microL each) was injected into the striatum of male Sprague-Dawley rats. The rats recovered for 1 to 72 hours before injection of [14C]-2-deoxyglucose (intraperitoneally) 30 minutes before decapitation. Animals were pretreated with the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonists dizolcilpine maleate (MK-801; 1 mg/kg) or 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline (NBQX; 30 mg/kg), or saline vehicle. Additional animals received intrastriatal injections of glutamate (1.0 mmol/L), NMDA (1.0 mmol/L), or AMPA (0.1 mmol/L) in the place of blood. Semiquantitative autoradiographs from the brains were analyzed to determine the effects of hemorrhage on relative glucose metabolism.', 'We found an acute phase of increased [14C]-2-deoxyglucose uptake in the perihematomal region that peaks 3 hours after lysed blood injection. Saline injections had no effect on striatal glucose utilization. The increased [14C]-2-deoxyglucose uptake produced by the hemorrhages was blocked by pretreatment with MK-801 and NBQX. Glutamate injections alone had no effect on striatal metabolism, whereas NMDA and AMPA injections increased [14C]-2-deoxyglucose uptake.",
            "output": [
                "Does glutamate receptor blockade attenuate glucose hypermetabolism in perihematomal brain after experimental intracerebral hemorrhage in rat?"
            ]
        },
        {
            "id": "task847-158a31addfea4754a937a8ae52476a09",
            "input": "Particulate air pollution is associated with cardiovascular diseases and myocardial infarction (MI).', 'We investigated the relationship between airway inflammation and thrombosis 24 hours after intratracheal (IT) instillation of diesel exhaust particles (DEP; 50 microg/hamster). Mild thrombosis was induced in the femoral vein by endothelial injury, and the consequences of airway inflammation on thrombogenicity were studied via online video microscopy. Lung inflammation and histamine analysis in bronchoalveolar lavage (BAL) and plasma were performed after pretreatment with dexamethasone (DEX) or sodium cromoglycate (SC). DEP induced airway inflammation and histamine release in BAL and in plasma, and increased thrombosis, without elevating plasma von Willebrand factor (vWF) levels. The IT instillation of 400-nm positively charged polystyrene particles (500 microg/hamster), serving as particles that do not penetrate into the circulation, equally produced airway inflammation, histamine release, and enhanced thrombosis. Histamine in plasma resulted from basophil activation. Intraperitoneal (IP) pretreatment with DEX (5 mg/kg) abolished the DEP-induced histamine increase in BAL and plasma and abrogated airway inflammation and thrombogenicity. The IT pretreatment with DEX (0.5 mg/kg) showed a partial but parallel inhibition of all of these parameters. Pretreatment with SC (40 mg/kg, IP) strongly inhibited airway inflammation, thrombogenicity, and histamine release.",
            "output": [
                "Does pharmacological stabilization of mast cells abrogate late thrombotic events induced by diesel exhaust particles in hamsters?"
            ]
        },
        {
            "id": "task847-6809cbd2c53c4e94b131511552e3e893",
            "input": "Local lymph node involvement in adults with renal cell carcinoma (RCC) is associated with poor outcome. The prognostic significance of local lymph node involvement in children with RCC has not been studied systematically.', \"A retrospective review of patients treated at St Jude Children's Research Hospital (Memphis, TN) and an extensive review of the medical literature were undertaken to evaluate the prognostic significance of local lymph node involvement in pediatric RCC.\", \"Thirteen patients with the diagnosis of RCC were treated at St. Jude since the hospital's inception in 1962. Four patients presented with lymph node-positive, distant metastasis-negative (N + M0) disease, and all 4 remain disease free after resection without adjuvant therapy (follow-up duration, 2-9 years). A systematic review of the literature including 243 pediatric patients with RCC revealed stage-specific survival rates of 92.5%, 84.6%, 72.7%, and 12.7% for Stage I-IV disease, respectively. Of 58 children with N + M0 RCC for whom outcome data were available, 42 (72.4%) were alive without disease at last follow-up. Among patients whose therapy could be discerned, those who received no adjuvant therapy fared as well (15 of 16 alive) as those who received various adjuvant treatments (22 of 31 alive).",
            "output": [
                "Does local lymph node involvement predict poor outcome in pediatric renal cell carcinoma?"
            ]
        },
        {
            "id": "task847-4ff3a98a01224af7bb99910a93bd0874",
            "input": "Statin therapy in nonsurgical patient populations is associated with a significant reduction in adverse cardiovascular events, including death, myocardial infarction (MI), and stroke. Recently, statin therapy was shown to be associated with a reduced incidence of postoperative mortality in patients undergoing major noncardiac vascular surgery. We investigated the influence of preoperative statin therapy on adverse outcomes after primary coronary artery bypass graft (CABG) surgery.', 'A retrospective cohort study of patients undergoing primary CABG surgery with cardiopulmonary bypass (CPB) (n=1663) between January 1, 2000 and December 31, 2001 at the Texas Heart Institute was performed. Patients were classified into 2 groups: patients receiving preoperative statin therapy (n=943) and patients not receiving preoperative antihyperlipidemic therapy (n=720). To determine if preoperative statin therapy was independently associated with a reduction in the risk of adverse postoperative outcomes, multivariate stepwise logistic regression was performed controlling for patient demographics, medical history, and preoperative medications. Multivariate logistic regression analysis demonstrated that preoperative statin therapy was independently associated with a significant reduction ( approximately 50%) in the risk of 30-day all-cause mortality (3.75% versus 1.80%; P<0.05). The adjusted odds ratio for early mortality in patients receiving preoperative statin therapy compared with patients not receiving antihyperlipidemic agents was 0.53 (95% CI, 0.28 to 0.99). Statin therapy was not independently associated with a reduced risk of postoperative MI, cardiac arrhythmias, stroke, or renal dysfunction. In an attempt to further control for selection bias related to the choice of therapy, multivariate analysis of a propensity-matched cohort of 1362 patients revealed that preoperative statin therapy was independently associated with a significant reduction in the composite endpoint of 30-day all-cause mortality and stroke (7.1% versus 4.6%; P<0.05).",
            "output": [
                "Are statins associated with a reduced incidence of perioperative mortality after coronary artery bypass graft surgery?"
            ]
        },
        {
            "id": "task847-80699fda52ed4a89ac3967974564da9e",
            "input": "Hypertension is one of the most important risk factors for coronary heart disease. Recent studies have pointed out the possibility that virgin olive oil (VOO) may lower blood pressure in hypertensive (HT) subjects. However, until the date there is scarce information regarding elderly people. The present study was designed to assess the effect of dietary VOO on blood pressure in medically treated hypertensive elderly patients.', '31 medically treated HT elderly patients and 31 normotensive (NT) elderly volunteers participated in a randomized sequential dietary intervention. Subjects consumed diets enriched in sunflower oil (SO) or VOO for 4 weeks each with a 4-week washout period between them.', 'VOO reduced total and LDL-cholesterol in NT but not in HT (P < 0.01) and the concentrations were lower than in the group consuming SO. In contrast, no significant differences were found in the levels of tocopherols among the groups studied. Iron-induced oxidation of LDL resulted in a complete loss of monoacylglycerols (MG) and diacylglycerols (DG) and a reduction in triacylglycerols (TG) (60-80%), which was found to be greater in HT (P < 0.01) with no effect of diet. VOO consumption normalized systolic pressure in the HT group (136 +/- 10 mmHg) compared to SO (150 +/- 8 mmHg).",
            "output": [
                "Does virgin olive oil reduce blood pressure in hypertensive elderly subjects?"
            ]
        },
        {
            "id": "task847-ab85a23cab2e4f5fa8c187f2fd4ca713",
            "input": "Accumulation in the brain of small aggregates of amyloid beta-protein 42 (Abeta42) is the major pathogenic event of Alzheimer disease (AD). In familial early-onset AD this event is likely the result of Abeta42 overproduction; in the most common sporadic late-onset form of the disease the mechanisms of Abeta42 accumulation are unknown.', 'To address this issue the authors analyzed plasma levels of Abeta42 in 88 elderly patients with amnestic mild cognitive impairment (MCI), chosen as paradigm of preclinical sporadic AD.', 'The authors found a significant increase of Abeta42 plasma levels in women with MCI, in comparison to the affected men and 72 cognitively normal age-matched subjects. The levels were independent of variables in education, apolipoprotein E genotype, cholesterol, and creatinine plasma concentrations, as well as hemoglobin content.",
            "output": [
                "Are plasma levels of amyloid beta-protein 42 increased in women with mild cognitive impairment?"
            ]
        },
        {
            "id": "task847-6ec88960ac3c4b72a4f1e7e771e23cb0",
            "input": "Standard treatment for patients with multiple myeloma is debulking chemotherapy with non-alkylating agents followed by a regimen to mobilize peripheral blood stem cells (PBSC) and the transplantation of the mobilized, autologous PBSC. The aim of this study was to evaluate the efficacy of a new regimen and compare it with that of a previous regimen.', 'In a large cohort of 106 patients (group I) we administered a new pre-transplant program which includes 2 courses of pulsed-VAD (vincristine, adriamycin, dexamethasone) followed by 2 courses of DCEP (dexamethasone, cyclophosphamide, etoposide and cis-platinum). We compared the efficacy of this new VAD-DCEP sequence, in terms of mobilizing capacity, toxicity and anti-myeloma activity in comparison with that of the previous VAD-high-dose cyclophosphamide program (group II, 40 patients).', 'In group I 81/106 (76.4%) patients yielded >or= 4x10(6)/kg CD34+ cells, as did 30/40 (75%) in group II but with a significantly higher toxicity in this latter group. In detail, 9 patients in group I (8.5%) had WHO grade III neutropenia versus 35 in group II (87.5%), 5 patients of group I (4.7%) had grade III thrombocytopenia versus 12 patients in group II (30%), and 8 patients in group I (7.5%) experienced an infections fever versus 9 patients in group II (22.5%). Therefore, nearly all patients in group II had to be admitted to hospital (39/40, 97.5%). There was a higher percentage of responses (CR+VGPR+PR) in group I than in group II: 73% versus 50% (p=0.02).",
            "output": [
                "Is the VAD-DCEP sequence an effective pre-transplant therapy in untreated multiple myeloma?"
            ]
        },
        {
            "id": "task847-961fefa838a1444c87f14c9965b694da",
            "input": "To investigate the effect of wortmannin and 3-aminobenzamide (3-AB) on telomerase activity and apoptosis in two human leukaemia cells.', 'MOLT-4 (p53-wild type) and KG1a (p53-null) cells were irradiated with gamma-rays (3 Gy at 1.57 Gy min(-1)) and the effects of wortmannin and 3-AB were evaluated. Telomerase activity was measured by polymerase chain reaction and the expression of human telomerase reverse transcriptase, human telomerase RNA and telomerase-associated protein 1 was assessed by reverse transcriptase-polymerase chain reaction. Apoptosis was evaluated by fluorescence microscopy and flow cytometry.', 'A radiation-induced up-regulation of telomerase activity was observed from 4 h post-irradiation in both cell lines. This up-regulation was abrogated by wortmannin and 3-AB. Telomerase activity was maximal 24 h post-irradiation, coinciding with an accumulation of human telomerase reverse transcriptase mRNA. Apoptosis and G2/M arrest were evident from 4 h post-irradiation in MOLT-4 cells. KG1a cells exhibited a G2/M block at 24 h post-irradiation and apoptosis increased between 24 and 48 h post-irradiation. 3-AB abolished G2/M blockage and enhanced radiation-induced apoptosis in both cell lines, while wortmannin increased apoptosis only in MOLT-4 cells.",
            "output": [
                "Does pharmacological inhibition of DNA repair enzymes differentially modulate telomerase activity and apoptosis in two human leukaemia cell lines?"
            ]
        },
        {
            "id": "task847-1b974c09b307403d93aabb36545160f3",
            "input": "Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies.\", 'In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings) and we report here that nestin-positive (but not nestin-negative) mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1) this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2) anti-BMP4 antibodies inhibit the nestin-positive mesenchymal stem cells conditioned medium inducing effect on astrogliogenesis.",
            "output": [
                "Do nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4?"
            ]
        },
        {
            "id": "task847-96dfe1a641cf42318bb9e0f99556189b",
            "input": "The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication.', \"Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method.\", 'Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68.",
            "output": [
                "Does delta-9 tetrahydrocannabinol ( THC ) inhibit lytic replication of gamma oncogenic herpesviruses in vitro?"
            ]
        },
        {
            "id": "task847-86d62ffdfda44805ae42485cfd660b4b",
            "input": "To determine the acute effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, during exercise in patients with coronary artery disease.', 'Double blind, randomised, placebo controlled, crossover study.', 'Outpatients evaluated in an exercise test laboratory.', '15 patients with exercise induced myocardial ischaemia.', 'Maximal cardiopulmonary exercise test on a treadmill according to an individualised ramp protocol on three days. The first day was used for adaptation to the equipment and to determine exercise tolerance and the presence of exercise induced ischaemia. On the other two days, the cardiopulmonary exercise test was performed two hours after oral administration of pyridostigmine (45 mg) or placebo. All patients were taking their usual medication during the experiments.', 'Rate-pressure product and oxygen uptake during exercise.', 'Pyridostigmine inhibited the submaximum chronotropic response (p = 0.001), delaying the onset of myocardial ischaemia, which occurred at a similar rate-pressure product (mean (SE) placebo 20.55 (1.08) mm Hg x beats/min 10(3); pyridostigmine 19.75 (1.28) mm Hg x beats/min 10(3); p = 0.27) but at a higher exercise intensity (oxygen consumption: placebo 18.6 (1.7) ml/kg/min; pyridostigmine 19.6 (1.8) ml/kg/min; p = 0.03). Also, pyridostigmine increased peak oxygen consumption (placebo 23.6 (2) ml/kg/min; pyridostigmine 24.8 (2) ml/kg/min; p = 0.01) and peak oxygen pulse (placebo 12.9 (1) ml/beat; pyridostigmine 13.6 (1) ml/beat; p = 0.02).",
            "output": [
                "Does cholinergic stimulation with pyridostigmine protect against exercise induced myocardial ischaemia?"
            ]
        },
        {
            "id": "task847-af081f6a1cde48729c628d9a30e01b24",
            "input": "Diosgenin is a steroidal sapogenin with estrogenic and antitumor properties. In order to elucidate the mechanism of its antiproliferative activity, we investigated its effects on the cell cycle and apoptosis in human chronic myelogenous leukemia K562 cells.', 'Cell viability was assessed via an MTT assay. Apoptosis was investigated in terms of nuclear morphology, DNA fragmentation, and phosphatidylserine externalization. Cell cycle analysis was performed via PI staining and flow cytometry (FCM). Western blotting and immunofluorescence methods were used to determine the levels of p53, cell cycle-related proteins and Bcl-2 family members. FCM was also used to estimate the changes in mitochondrial membrane potential (MMP), intracellular Ca2+ concentration and reactive oxygen species (ROS) generation.', 'Cell cycle analysis showed that diosgenin caused G2/M arrest independently of p53. The levels of cyclin B1 and p21Cip1/Waf1 were decreased, whereas cdc2 levels were increased. Subsequent apoptosis was demonstrated with the dramatic activation of caspase-3. A dramatic decline in intracellular Ca2+ concentration was observed as an initiating event in the process of cell cycle arrest and apoptosis, which was followed by the hyperpolarization and depolarization of MMP. Generation of ROS was observed in the progression of apoptosis. The antiapoptotic Bcl-2 and Bcl-xL proteins were downregulated, whereas the proapoptotic Bax was upregulated.",
            "output": [
                "Does diosgenin induce cell cycle arrest and apoptosis in human leukemia K562 cells with the disruption of Ca2+ homeostasis?"
            ]
        },
        {
            "id": "task847-7e2187f49ad7416ab28deb413e5e655f",
            "input": "Advanced gene therapy, tissue engineering and biopharmaceutical manufacturing require sophisticated and well-balanced multiregulated multigene interventions to reprogram desired mammalian cell phenotypes.', 'We have combined the streptogramin (PIP)- and tetracycline (TET)-responsive gene regulation systems for independent expression control of the differentiation determinants myoD and msx1 in C2C12-derived cells.', 'Different dual-regulated expression scenarios which induce either both, only one or none of the lineage control genes triggered differential differentiation and precise control of myogenic, osteogenic or adipogenic cell phenotypes.",
            "output": [
                "Do dual-regulated myoD- and msx1-based interventions in C2C12-derived cells enable precise myogenic/osteogenic/adipogenic lineage control?"
            ]
        },
        {
            "id": "task847-3ddec5a56928412daee948c974cdebc8",
            "input": "Numerous studies have demonstrated cerebellar activity during implicit motor learning, but few have addressed its specific role. The purpose of this study was to determine if specific components (spatial or temporal) of an implicit motor-tracking task were affected by cerebellar stroke.', 'The authors studied the performance of individuals with unilateral cerebellar stroke (n = 7)and a control group (n = 10) across 3 acquisition days and at a delayed retention test as they practiced a unimanual tracking task with the contralesional upper extremity.', 'After cerebellar stroke, participants demonstrated reduced tracking errors for repeating sequences compared to random sequences; however, decomposition of tracking performance into temporal and spatial components revealed persistent deficits in tracking time lag despite improved spatial accuracy. A lesion analysis showed that the dentate nucleus was the only common region affected by all cerebellar strokes.",
            "output": [
                "Does cerebellar stroke impair temporal but not spatial accuracy during implicit motor learning?"
            ]
        },
        {
            "id": "task847-2438d375d9c24cf29750ef5f11235c48",
            "input": "Low plasma IgG levels have long been reported as an important complication of the nephrotic syndrome. Few studies in vivo have evaluated IgG synthesis in nephrotic patients and no data are available on the effect of dietary protein restriction on the rate of IgG synthesis.', 'We compared the IgG synthesis rates of seven nephrotic patients who assumed, for 4 weeks, either a normal protein diet (NPD) (1.20+/-0.06 g/kg/day) or a low-protein diet (LPD) (0.66+/-0.04 g/kg/day) with those of seven normal subjects (matched for age and body mass index). The post-absorptive fractional synthesis rate (FSR) and absolute synthesis rate (ASR) of IgG were evaluated during the last 120 min of a 5 h 5,5,5-D3-l-leucine infusion.', 'Compared with controls, in nephrotic patients the plasma IgG levels and pool were significantly reduced (P<0.05), while IgG FSR and ASR were increased by 4- and 2.5-fold, respectively (P<0.05). The LPD regimen did not affect plasma IgG FSR, ASR, circulating concentrations and intravascular pool (P = NS). There was a significant negative correlation between plasma IgG FSR and the IgG intravascular pool in nephrotic patients evaluated during both the NPD (r = -0.828; P<0.05) and LPD (r = -0.861; P<0.05) regimens.",
            "output": [
                "Does dietary protein intake affect IgG synthesis in patients with nephrotic syndrome?"
            ]
        },
        {
            "id": "task847-acce7208a6cc40759db84ac3472dbb79",
            "input": "We demonstrated previously that striatal adenosine modulates ethanol-induced motor incoordination (EIMI) via adenosine A1 receptors coupled to pertussis toxin (PT)-sensitive G protein and adenylyl cyclase-cyclic adenosine monophosphate (cAMP). Additionally, intrastriatal (IST) PT antagonizes EIMI and its potentiation by the adenosine A1 agonist N-cyclohexyladenosine; it also inhibits cAMP concentration.', 'Guide cannulas were stereotaxically implanted for IST pretreatment with PT followed 5 days later by IST of N-cyclohexyladenosine and intraperitoneal ethanol. The adenosine diphosphate (ADP) ribosylation reaction involved PT-catalyzed [P]nicotinamide adenine dinucleotide (NAD) labeling of rat striatal membranes. Antagonism of EIMI (Rotorod method) after IST microinfusion of PT was investigated to determine whether it was due to a decrease in the functional activity of G proteins due to ADP ribosylation of the Gialpha subunit caused it.', 'Striatal membranes from IST PT (0.5 microg)-treated animals exhibited significantly attenuated (up to 90%) in vitro ADP ribosylation with [P]NAD. Striatal membranes from animals injected with ethanol (1.5 g/kg intraperitoneally) exhibited statistically significant increase (11%) in in vitro ADP ribosylation. Similarly, ethanol (50 mM) added to striatal membranes from untreated animals produced significant stimulation of in vitro ADP ribosylation. The decrease in the functional activity of G proteins due to ADP ribosylation of the Gialpha subunit after IST PT was functionally correlated with marked attenuation in EIMI, as observed previously. This finding suggests a blockade of functional activity of PT-sensitive striatal Gi/Go proteins (i.e., fewer available sites for labeled NAD incorporation). The in vivo ethanol results indicate that it must have caused an increase in the ribosylation capacity of Gialpha in vivo (i.e., increased Gi activity). Increased ADP ribosylation by in vitro ethanol increases Gi/Go activity, consistent with EIMI, as previously reported.",
            "output": [
                "Does acute ethanol-induced adenosine diphosphate ribosylation regulate the functional activity of rat striatal pertussis toxin-sensitive g proteins?"
            ]
        },
        {
            "id": "task847-30bbce5a34b046949d649875298f390d",
            "input": "Chronic ethanol (EtOH) has been shown to augment tumor necrosis factor (TNF)-alpha production, and this has been associated with EtOH-induced liver injury. We have recently described a chronic in vitro cell culture model where chronic ethanol exposure results in significantly augmented TNF production in Mono Mac 6 cells, a human monocytic cell line. This enhanced TNF production was redox regulated and associated with increased levels of TNF messenger RNA (mRNA) as well as increased processing of TNF by TNF converting enzyme (TACE), the enzymatic activity of which is regulated by the cellular redox state. We hypothesized that chronic ethanol through oxidative stress activates TACE-mediated ectodomain shedding of the preformed substrates p75 and p55 TNF receptors in Mono Mac 6 cells and L-selectin in Jurkat T cells.', 'Mono Mac 6 or Jurkat T cells were treated with EtOH (0, 50, or 100 mM) for 4 to 6 days. Shedding of p75 and p55 TNF receptors (Mono Mac 6 cells) or L-selectin (Jurkat T cells) was induced by stimulation with lipopolysaccharide and phorbol myristate acetate for Mono Mac 6 cells and PMA alone for Jurkat T cells. Shedding was assessed by enzyme-linked immunosorbent assay for shed molecules in the cell supernatant as well as the cell-associated proteins recovered from cell pellets. Steady-state mRNA levels for p75 TNF receptor and L-selectin were determined by ribonuclease protection assay. Cell surface L-selectin and TACE were measured by flow cytometry, and cell associated p55 and p75 TNF receptors were measured by enzyme-linked immunosorbent assay.', 'Chronic EtOH exposure for 6 days resulted in a significant dose-dependent increase in shedding of p75 and p55 TNF receptors from Mono Mac 6 cells and L-selectin from Jurkat T-cells. The enhanced shedding was correlated with an alcohol-induced increase in mRNA levels and cell surface protein levels for these TACE substrates. Although chronic EtOH exposure increased the total amount of p75 and p55 TNF receptor and L-selectin shed into the media, the efficiency of shedding was suppressed by EtOH. In the case of Mono Mac 6 cells, the EtOH exposure increased superoxide production. Inhibition of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase and hydrogen peroxide partially prevented the increased production of p75 TNF receptor in these cells.",
            "output": [
                "Does chronic ethanol enhance ectodomain shedding in T cells and monocytes?"
            ]
        },
        {
            "id": "task847-d86de7ef7d4340f4b2fcf8a772e395ae",
            "input": "Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention.', \"The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML).\", 'Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level.",
            "output": [
                "Does implicit strategy affect learning in children with heavy prenatal alcohol exposure?"
            ]
        },
        {
            "id": "task847-d7acd7d4957645c4b49df76561d3d885",
            "input": "Serum levels of the tumor marker tissue polypeptide specific antigen (TPS, cytokeratin 18 fragments) are increased in patients with alcoholic liver disease, particularly in cases of alcoholic hepatitis. Mallory bodies, characteristic of alcoholic hepatitis, are cytokeratin 8 and 18 aggregates. The study was aimed at investigating the possible relationship of serum TPS levels with hepatocyte cytokeratin expression in patients with alcoholic liver disease.', 'Twenty-four patients with alcoholic liver disease were studied. Immunohistochemical staining for cytokeratins 8 and 18 was performed in liver specimens by means of CAM 5.2 monoclonal antibody. The number of hepatocytes containing CAM 5.2-reactive cytokeratin inclusions was compared with serum TPS levels.",
            "output": [
                "Are serum levels of tissue polypeptide specific antigen correlated with hepatocyte cytokeratin expression in alcoholic liver disease?"
            ]
        },
        {
            "id": "task847-3c19850775944bc9975639ca267206a0",
            "input": "Previous studies focusing on the changes of heart rate, systolic blood pressure and dyspnea caused by the six-minute (6MWT) and shuttle walking distance tests (ISWT) have produced conflicting data. The present study aims at comparing the cardiovascular and dyspnea responses to 6MWT and ISWT in patients with chronic obstructive pulmonary disease (COPD). Twenty patients with clinically stable COPD (age, 56 +/- 9 yrs; BMI, 27.8 +/- 7.7 kg.m(-2); FEV1%pred, 42 +/- 19%; mean +/- Sx) performed three 6MWTs and two ISWTs using standardised protocols. The distances walked in the third 6MWT and second ISWT were 458 +/- 105 and 365 +/- 116 m, respectively. There was a significant correlation between the distances covered in the two tests (r = 0.87; p < 0.001). The 6MWT and ISWT showed similar correlation coefficients with the Baseline Dyspnea Index (r = 0.86; p < 0.001 and r = 0.76; p < 0.001), the Clinical Symptom Scale (r= -0.72; p < 0.001 and r= -0.55; p = 0.011), FEV1 L (r = 0.36; NS and r = 0.30; NS), PImax (r = 0.59; p < 0.008 and r = 0.60; p = 0.001) and the mean pulmonary artery pressure, Doppler echocardiography (r= -0.51; p < 0.029 and r = -0.51; p = 0.032). Although the response to ISWT tended to be greater, we found no statistically significant differences between the two tests in the changes of heart rate (HR), systolic blood pressure (SBP) and dyspnea (Borg) (deltaHR, 17.9 +/- 13.4 vs 23.8 +/- 15.4; deltaSBP, 7.7 +/- 14.6 vs 13.0 +/- 17.0 and deltaBorg, 1.7 +/- 1.1 vs 2.2 +/- 0.9; NS).",
            "output": [
                "Do cardiovascular and dyspnea response to six-minute and shuttle walk tests in COPD patients?"
            ]
        },
        {
            "id": "task847-9b1d7ad8057f45a5bad02107c3682910",
            "input": "The mechanisms involved in the beneficial effect of gadolinium chloride against endotoxin-induced liver damage were studied.', 'Superoxide anions released into the hepatic sinusoids were examined in a liver perfusion model using the cytochrome C method.', 'Gadolinium chloride treatment fully depleted ED2-positive cells from the liver and significantly attenuated superoxide anion release after a lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha) challenge. Moreover, gadolinium chloride treatment resulted in a significant decline in endothelial cell damage in the hepatic sinusoids as assessed by the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in the liver perfusate. Although gadolinium chloride treatment did not affect the level of serum TNF-alpha, it significantly reduced that of interleukin (IL)-8 and neutrophil migration in the hepatic sinusoids after the lipopolysaccharide challenge.",
            "output": [
                "Does kupffer cell depletion attenuate superoxide anion release into the hepatic sinusoids after lipopolysaccharide treatment?"
            ]
        },
        {
            "id": "task847-6a58589b38d74b3aac867dbb802b5081",
            "input": "Clinical and experimental studies have shown that a reduction in myocardial glucose utilization is a factor contributing to diabetic cardiomyopathy. This study determined whether exercise training could prevent the depression in glucose utilization observed in the diabetic rat heart.', 'Diabetes was induced in Sprague-Dawley rats by an intravenous injection of streptozotocin (60 mg/kg). After 10 weeks of treadmill running, exogenous myocardial glucose utilization and cardiac function were determined in isolated working hearts perfused under aerobic conditions and then subjected to a 60-min period of low-flow ischemia followed by reperfusion.', 'Compared to aerobically perfused sedentary control hearts, rates of myocardial glucose oxidation and glycolysis were lower in diabetic hearts. Diabetes was also characterized by a pronounced decrease in cardiac function. Following exercise training, rates of myocardial glucose oxidation and glycolysis were restored and cardiac performance was improved compared to sedentary diabetic hearts. During low-flow ischemia, the decrease in glycolysis observed in hearts of sedentary diabetic rats was attenuated following exercise training. Following ischemia, glucose oxidation and glycolysis returned to preischemic levels in all groups. However, hearts from trained diabetic animals had higher rates of glucose oxidation compared to their respective sedentary group. This was accompanied by an enhanced recovery of heart function following ischemia.",
            "output": [
                "Does exercise training restore abnormal myocardial glucose utilization and cardiac function in diabetes?"
            ]
        },
        {
            "id": "task847-77af4296f494444b999389ce6724bcfc",
            "input": "Anal complaints, caused not by haemorrhoids but by anal folds, fissures or perianal thrombosis, are probably too often and wrongly attributed to haemorrhoids by patients and self-treated. It was the aim of this study to find out how frequently patients with anal complaints make this false assumption and how successful their self treatment is.', \"458 consecutive patients referred between May and November 2001 with unclear abdominal and/or anal symptoms were investigated by a standardized questionnaire/interview, including any experience with wet compresses, haemorrhoidal ointments or results of a doctor's treatment of haemorrhoids. They were then examined by procto-coloscopy. The findings were documented on the questionnaire and the data stored in an computer.\", '344 of the 548 patients (63 %) believed that they had haemorrhoids, 184 (34 %) did not think so, and 20 (3 %) left the question unanswered. Haemorrhoids were found to be present in 18 % and 13 %, respectively. Bleeding, pain, itching and burning sensation around the anus were the most common symptoms in both groups. 151 of the 184 patients who did not think they had haemorrhoids (82 %) had been previously treated by a doctor for \"haemorrhoids\". 28 % of this group of patients and 36 % of those thought to have haemorrhoids had similar results with wet compresses, creams or ointments, and the two groups were also similar regarding the number found to have anal disease.",
            "output": [
                "Are [ Haemorrhoids too often assumed and treated . Survey of 548 patients with anal discomfort ]?"
            ]
        },
        {
            "id": "task847-498af9a0f6144ddc81ca0d40d3219367",
            "input": "In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation.', 'LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages (RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol (baseline versus after treatment, 1.30+/-0.19 versus 1.48+/-0.28 mmol/L; P=0.002) and HDL/LDL ratio (0.31+/-0.01 versus 0.34+/-0.10; P=0.048), but lower serum LPS concentration (1.70+/-0.49 versus 0.98+/-0.50 ng/mL; P=0.004) and autoantibodies to beta2-glycoprotein I (0.11+/-0.06 versus 0.09+/-0.04 ELISA units; P=0.022) after treatment.",
            "output": [
                "Does severe periodontitis enhance macrophage activation via increased serum lipopolysaccharide?"
            ]
        },
        {
            "id": "task847-2b6aa20a1bde42ce9f9bfef56bd6df8b",
            "input": "We investigated the prevalence of anxiety and depressive symptoms in patients with an implantable cardioverter defibrillator (ICD) and their partners, and the role of personality factors and social support as determinants of distress.', 'Of all surviving patients (n = 221) having had an ICD implanted between October 1998 and January 2003, 182 patients and 144 partners completed the Hospital Anxiety and Depression Scale, the Type D Personality Scale, and the Perceived Social Support Scale. Type D personality defines those who tend to experience increased negative distress and who do not express these negative emotions in social interactions. Clinical variables for the patients were obtained from medical records.', 'Thirty-one percent of patients versus 42% of partners suffered from symptoms of anxiety (p =.048); symptoms of anxiety were particularly prevalent in male partners. Twenty-eight vs. 29% suffered from depressive symptoms (p =.901). In patients, Type D personality was independently related to anxiety (OR: 7.03; 95% CI: 2.32-21.32) and depressive symptoms (OR: 7.40; 95% CI: 2.49-21.94) adjusting for all other variables. Underlying cardiac disease pathology did not explain differences in patient distress. In partners, Type D personality was independently associated with increased symptoms of anxiety (OR: 8.77; 95% CI: 3.19-24.14) and depression (OR: 4.40; 95% CI: 1.76-11.01).",
            "output": [
                "Is type D personality associated with increased anxiety and depressive symptoms in patients with an implantable cardioverter defibrillator and their partners?"
            ]
        },
        {
            "id": "task847-ea878ea3222e4ef2b0f0c68a916cd44d",
            "input": "Depression is a common problem in patients with obstructive sleep apnea. The objective of this study was to examine whether depression is independently associated with lower self-reported sleep quality in patients with obstructive sleep apnea (OSA), after controlling for polysomnographic measures of sleep.', \"The sample comprised 135 patients who had been referred to a university teaching hospital's multidisciplinary sleep medicine center for polysomnographic evaluation of OSA. The median age of the subjects was 45 (mean age, 46 years) 55% were female, 69% were white, 31% were black, and their mean body mass index was 37.9 +/- 11.2 kg/m2. Self-reported sleep quality during the past 2 weeks was assessed by the insomnia severity index. Polygraphic measures of sleep quality included the respiratory disturbance index, sleep onset latency, arousals for no apparent reason, sleep efficiency, and periodic leg movements associated with arousal. Depressive symptoms were assessed by the Beck Depression Inventory.\", 'None of the polygraphic measures of sleep quality was related to self-reported sleep quality or depression. Oxygen desaturation was correlated with self-reported sleep quality (r = 0.21, p =.02). Depression correlated with self-reported sleep quality (r = 0.55, p <.0001). In a multiple regression analysis, depression remained a significant predictor of self-reported sleep quality after controlling for all of the polysomnographic measures of sleep quality (F = 9.65, partial r2 = 0.28 p =.0001).",
            "output": [
                "Does depression predict self-reported sleep quality in patients with obstructive sleep apnea?"
            ]
        },
        {
            "id": "task847-c0e2b9c44aa44deda7b2fa924d4fe11c",
            "input": "The current study examined the relation of anger, hostility, and severity of depressive symptoms, alone and in combination, to C-reactive protein (CRP) in healthy men and women.', 'A high sensitivity enzyme linked immuno sorbent assay (ELISA) was used to evaluate CRP levels in a multiethnic sample of 127 healthy, nonsmoking men and women. Fasting blood samples were collected the same day the assessments were done of anger and hostility using the Buss-Perry Aggression Questionnaire (BPAQ) and depressive symptomatology using the Beck Depression Inventory (BDI). A psychological risk factor (PRF) score representing a composite summary indicator of BDI and BPAQ-anger and -hostility was generated using principal component analysis. Log-transformed CRP values were examined using univariate and multivariate analyses adjusting for control variables of age, gender, body mass index (BMI), alcohol use, exercise frequency, ratio of total to high-density lipoprotein cholesterol, and family history of premature coronary heart disease (CHD).', 'Log-normalized CRP was correlated with BDI (r = 0.21, p =.02) and BPAQ anger (r = 0.20, p =.02), but not with BPAQ hostility. After adjustment for control variables, BDI (beta = 0.05, p =.011), BPAQ anger (beta = 0.05, p =.007), and the PRF composite score (beta = 0.27, p =.005), but not BPAQ hostility (beta = 0.03, p =.11), were significantly associated with log-normalized CRP.",
            "output": [
                "Is c-reactive protein associated with psychological risk factors of cardiovascular disease in apparently healthy adults?"
            ]
        },
        {
            "id": "task847-54e7bfddc37d4893a14a43ea304f6e61",
            "input": "The modern multimodality therapeutic approach to Wilms tumor (WT), combining surgery with radiotherapy and chemotherapy results in high cure rates even for high stage disease. However, the combination of radiotherapy and chemotherapy is associated with severe early and late complications such as neutropenic sepsis, growth retardation and secondary malignancies. Therefore, novel therapeutic strategies, which would decrease the treatment burden, are required. We studied the expression of erbB2 growth factor receptor in WT cells as well as its role as a tumor therapeutic target in an in vivo xenograft model of Wilms tumor.', 'Paraffin embedded pathological samples from 14 different WT cases as well as xenografts derived thereof were immunostained with anti-erbB2 monoclonal antibody. The immunostaining was graded in comparison to a known positive control (breast cancer) and was scored by the intensity of staining (0 to +3) multiplied by the percentage of cells expressing the antigen. The expression of erbB2 in the human WT xenograft was verified also by fluorescence activated cell sorter analysis. In addition, nude mice bearing established subcutaneous human WT xenografts were treated with either 3 intraperitoneal injections of N29 anti-erbB2 monoclonal antibody or irrelevant antibody.', 'All of the authentic human pathological samples, except 1 anaplastic WT as well the WT xenografts (at different stages), expressed erbB2. Expression was also observed in WT metastasis and in tumors which out grew chemotherapy. Systemic administration of anti-erbB2 monoclonal antibody inhibited and even prevented the growth of WT xenograft in vivo.",
            "output": [
                "Is erbB2 a tumor associated antigen and a suitable therapeutic target in Wilms tumor?"
            ]
        },
        {
            "id": "task847-37795789e2674b278d88031ce34dbeb1",
            "input": "To investigate the impact of possession of the -889 C/T polymorphism of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the interleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alzheimer's disease (AD), as demonstrated by the degree of microglial cell activity associated with each IL-1A and IL-1B genotype.\", 'Microglial cell activity within the frontal cortex was determined in 68 patients with necropsy confirmed AD by image analysis as the percentage area of tissue occupied by ferritin immunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracted from frontal cortex or cerebellum.', 'The microglial cell load was 31% greater in patients with IL-1A T allele, 62% greater with IL-1A TT genotype, but 108% greater with IL-1A TT genotype in combination with APOE epsilon4 allele. No effects on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone.",
            "output": [
                "Does a polymorphic variation in the interleukin 1A gene increase brain microglial cell activity in Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-7c20a03d04184535b5794ff253d8b10f",
            "input": "CYR61 is an extracellular matrix-associated protein that promotes adhesion, migration, and proliferation of endothelial cells and fibroblasts. Prostate enlargement, which frequently causes the urethral compression, is often histologically observed as stromal and epithelial hyperplasia in an enlarged gland. To determine whether or not CYR61 has relevance to the progression of benign prostatic hyperplasia (BPH), we investigated the induction of CYR61, and also examined its function in both prostatic stromal and epithelial cells.', 'Recombinant CYR61 protein was used for the examination of the activity of CYR61 as to cell adhesion and proliferation. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was utilized to screen for inducers of the CYR61 gene in prostatic cells. Finally, the effects of an anti-sense oligonucleotide, which could reduce the production of CYR61, on the morphology and growth of prostatic cells were also examined.', 'Recombinant CYR61 protein promotes prostatic cell adhesion and proliferation. The mRNA for CYR61, a growth factor-inducible immediate early gene, was markedly induced by fetal bovine serum (FBS) within 1 hr, and strongly induced by transforming growth factor-beta1 (TGF-beta) for at least 19 hr following stimulation. The suppression of CYR61 production with an anti-sense oligonucleotide causes obvious morphological changes of prostatic cells. Furthermore, we have shown that CYR61 is necessary, at least in part, for FBS-induced prostatic cell proliferation, because dramatic inhibition of cellular growth was caused by the suppression of CYR61 production with the addition of the anti-sense oligonucleotide before FBS stimulation.",
            "output": [
                "Is induction and function of CYR61 ( CCN1 ) in prostatic stromal and epithelial cells : CYR61 required for prostatic cell proliferation?"
            ]
        },
        {
            "id": "task847-e981ad35362140eeb34fda2549d1014a",
            "input": "The purpose of the current study was to determine whether there is any incremental benefit to routine intravascular ultrasound (IVUS) guidance of percutaneous coronary intervention.', 'We compared the outcome of 796 patients who underwent an IVUS study (IVUS group) during the index stent procedure with 8274 patients who did not have an IVUS study (angiography group). The primary end point was the composite end point of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months of the index stent procedure. There were statistically significant differences in multiple procedural characteristics. Most importantly, those patients who underwent an IVUS study had a larger postprocedural minimal lumen diameter and smaller postprocedural percent diameter stenosis. However, there was no significant difference between the IVUS group and the angiography group with respect to the primary end point (RR 1.10, 95% CI 0.91, 1.32) or any of the individual clinical end points. Adjustment for multiple clinical and procedural characteristics did not significantly alter these findings.",
            "output": [
                "Is routine intravascular ultrasound scanning guidance of coronary stenting associated with improved clinical outcomes?"
            ]
        },
        {
            "id": "task847-4d3524d1768e4ef5ab2022411602f091",
            "input": "Anosognosia is a common manifestation of Alzheimer's disease. There is an association between impaired awareness and frontal-executive cognitive deficits. Anosognosia is also correlated with decreased metabolism in the right hemisphere, particularly in frontal lobe regions.\", \"To investigate pathological correlates of anosognosia in Alzheimer's disease.\", \"41 subjects followed longitudinally in the University of Pittsburgh memory disorders clinic and with necropsy verified Alzheimer's disease were divided into two groups, based on previous clinical assessment: +Aware (n = 23) and -Aware (n = 18). A subset analysis matching subjects for dementia severity using mini-mental state examination scores was also carried out (13 +Aware; 13 -Aware). Histopathological data from necropsy brain tissue consisted of senile plaque (SP) and neurofibrillary tangle (NFT) counts (regional density) from four different brain regions in the right and left hemispheres: superior and middle frontal gyri (SMF), superior temporal isocortex (ST), the prosubiculum of the hippocampus (PRO), and the entorhinal cortex (EC).\", 'SP density was greater in the right PRO region of -Aware subjects (F = 6.54, p = 0.015) than +Aware subjects. Significant differences between SP or NFT density were not observed in any other regions. In the subset analysis matching for dementia severity, SP density was again greater in the right PRO region of -Aware subjects than in the other regions (F = 12.72, p = 0.002).",
            "output": [
                "Does right prosubiculum amyloid plaque density correlate with anosognosia in Alzheimer 's disease?"
            ]
        },
        {
            "id": "task847-38518b7c73394b1b805491ce57d1a9e8",
            "input": "Although uncommon, hearing loss after spinal anesthesia has been described. Vestibulocochlear dysfunction after spinal anesthesia in which 22-gauge and 25-gauge Quincke needles were used was investigated to determine if needle size affected hearing.', 'Patients with American Society of Anesthesiologists physical status I and II, aged 20 to 40 years, who were undergoing lower extremity surgery under spinal anesthesia were randomized into 2 groups. After intravenous hydration, 3 mL of 0.5% bupivacaine was administered for spinal anesthesia, which was performed with a 22-gauge Quincke needle in group I (n=30) patients and a 25-gauge Quincke needle in group II (n=30) patients. Before surgery and 2 days after surgery, pure-tone audiometry and tympanometry were performed. Preoperative and postoperative hearing data were obtained in the right and left ears for every frequency. Headache, nausea, and vomiting and cranial nerve III, IV, V, VI, VII, and VIII function were assessed on postoperative day 2.', 'Demographic data were not different between the groups. No hypoacousis was noted at any frequency during the entire testing period in either group. Two patients from group I experienced postdural puncture headache on postoperative day 3, and neither had hearing loss. No patient had cranial nerve dysfunction.",
            "output": [
                "Does hearing loss occur in young patients undergoing spinal anesthesia?"
            ]
        },
        {
            "id": "task847-148f0bb7f51a488c8bc1509c1818f138",
            "input": "To examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health.', 'Persons with Type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. Brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. The primary outcome was change in brachial artery endothelial function from baseline. Comparison of randomized groups was a secondary aim.', 'Eighty-six participants were randomized, and 83 were followed to study completion. Post occlusion brachial artery vasodilation was 3.74% at baseline and 3.82% following 16 weeks of therapy (P = 0.77). The treatment effect was 0.08% (95% CI: -0.48%, 0.64%). No difference was seen between treatment groups (P = 0.69). Overall, A1C was reduced from 8.3% to 7.0%, with a greater reduction in the combination therapy group (from 8.4% to 6.7%) than in the monotherapy group (from 8.3% to 7.3%, p for difference between groups = 0.01). Statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. Statistically significant increases were observed for fasting insulin, uric acid, weight and BMI.",
            "output": [
                "Does the combination oral and nutritional treatment of late-onset diabetes mellitus ( CONTROL DM ) trial result?"
            ]
        },
        {
            "id": "task847-f0dcf8ee1a3f407481c37a6e74bf38bd",
            "input": "To investigate the relationship between follicular blood flow and the follicular fluid vascular endothelial growth factor (VEGF) and nitric oxide (NO) concentrations and to determine which factor might be a better predictor of the outcome of IVF-ET.', 'Prospective study.', 'Academic research laboratory.', 'Forty-seven cycles of IVF (tubal factor, 25 cycles; male factor, 22 cycles) at the infertility clinic of Pusan National University Hospital from February 2002 to June 2002.', 'Follicular blood flow was estimated on the day of hCG administration. Each follicular fluid sample was collected at oocyte retrieval, and follicular fluid VEGF and NO concentrations were assessed.', 'Follicular blood flow and follicular fluid VEGF and NO concentrations according to the age of patients, the cause of infertility, and pregnancy rate.', 'Of 47 cycles, 18 (38.3%) cycles resulted in a pregnancy. Follicular blood flow was significantly higher in the pregnant group compared with the nonpregnant group, but there was no statistically significant difference in age and infertility cause. Follicular fluid concentrations of VEGF and NO did not show statistically significant differences in age, infertility cause, or pregnancy outcome. As the follicle size increases, the follicular blood flow and follicular fluid VEGF concentrations increased significantly but the follicular fluid NO concentrations decreased. There was no correlation between VEGF and NO concentrations in the follicular fluid by linear regression analysis.",
            "output": [
                "Is follicular blood flow a better predictor of the outcome of in vitro fertilization-embryo transfer than follicular fluid vascular endothelial growth factor and nitric oxide concentrations?"
            ]
        },
        {
            "id": "task847-a19d6c80a3ed42adb3c0514801119b34",
            "input": "The receptor activator of NF-kB ligand (RANKL) has a critical role in osteoclast activation. Recently it has been demonstrated that human multiple myeloma (MM) cells do not express RANKL but up-regulate RANKL in bone marrow stromal cells (BMSC). To further investigate the role of RANKL in the pathophysiology of MM we evaluated the expression of its receptor RANK in MM cells and in the BM environment and the potential role of RANKL in the interaction of myeloma cells with the microenvironment.', 'RANK mRNA and protein expression were evaluated by reverse transcription polymerase chain reaction and Western blot analysis in human myeloma cell lines (HMCL), fresh purified MM cells, BMSC and endothelial cells. Moreover the effect and the role of RANKL on cytokine secretion were evaluated in BMSC, in endothelial cells and in co-culture conditions with myeloma cells.', 'We found that RANK is expressed in BMSC and endothelial cells but not in myeloma cells. Consistently, RANKL did not have a direct effect on myeloma cell survival, but RANKL treatment induced a significant increase of interleukin (IL)-6 and IL-11 secretion by both BMSC and endothelial cells. Moreover, in a co-culture system we found that myeloma cells up-regulated both IL-6 and IL-11 secretion by BMSC and endothelial cells through cell-to-cell contact. The presence of the RANK-Fc that blocks the RANK/RANKL interaction significantly inhibited HMCL-induced secretion of IL-6 and IL-11.",
            "output": [
                "Is the RANK/RANK ligand system involved in interleukin-6 and interleukin-11 up-regulation by human myeloma cells in the bone marrow microenvironment?"
            ]
        },
        {
            "id": "task847-c26f27390fe24334ad6a402d47006361",
            "input": "To evaluate the Gram stain with carbol-fuchsin counterstain for the rapid detection of Campylobacter species in faecal samples.', 'In total, 842 consecutive diarrhoeic faecal samples were prospectively examined for Campylobacter species by Gram stain and culture.', 'Campylobacter species were isolated from 84 faecal samples (all Campylobacter jejuni). Compared with culture, Gram stain microscopy had a sensitivity of 89%, specificity of 99.7%, positive predictive value of 97%, and negative predictive value of 99% for detecting Campylobacter species.",
            "output": [
                "Do detection of Campylobacter species in faecal samples by direct Gram stain microscopy?"
            ]
        },
        {
            "id": "task847-ca177a7b932340e6af5f4e57db200f84",
            "input": "To evaluate the efficacy and safety of the combination of ICE (ifosfamide 1.5 g m(-2), carboplatin 100 mg m(-2) and etoposide 150 mg m(-2), days 1-4, q 28 days, G-CSF 5 microg kg(-1) starting from day 6) alone and in combination with regional hyperthermia (RHT) in soft tissue sarcoma (STS) refractory to previous standard doxorubicin-ifosfamide-based chemotherapy.', 'Twenty patients with advanced STS of different histological sub-types were treated with the ICE regimen with 13 patients receiving additional RHT. A median of four courses of ICE were administered with RHT on days 1 and 3 (60 min, T(max) 42 degrees C).', 'The objective response rate was 20%, with four partial responses (all treated with hyperthermia). In addition, two patients showed mixed responses and five patients stable disease. After a median follow-up time of 15 months, median time to progression was 6 months. Progression free rate estimates were 60% and 45% at 3 and 6 months, respectively. Median overall survival for all patients was 14.6 months.",
            "output": [
                "Is ifosfamide , carboplatin and etoposide ( ICE ) as second-line regimen alone and in combination with regional hyperthermia active in chemo-pre-treated advanced soft tissue sarcoma of adults?"
            ]
        },
        {
            "id": "task847-d56955e3a8254a63b2161f493208ecda",
            "input": "The aim of this study was to investigate whether risk factors for embolism would promote thrombus formation in patients with nonvalvular atrial fibrillation (NVAF).', 'Hemostatic markers for platelet activity (ie, platelet factor-4 and beta-thromboglobulin [TG]), thrombotic status (ie, prothombin fragments 1 and 2), and fibrinolytic status (ie, d-dimer) were determined in 246 patients with NVAF (mean age, 66.1 years) and 111 control subjects without NVAF (68.3 years).', 'The beta-TG level was higher in NVAF patients than in control subjects. D-dimer levels were higher in NVAF patients having risk factors (mean [+/- SE] d-dimer level, 158.6 +/- 9.2 ng/mL) than in those without risk factors (mean d-dimer level, 92.1 +/- 6.7 ng/mL; p < 0.01) and in control subjects (mean d-dimer level: control subjects with risk factors, 79.1 +/- 10.3 ng/mL; control subjects without risk factors, 31.0 +/- 7.4 ng/mL; p < 0.01). NVAF (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.87 to 8.30; p = 0.0003) and age of >/= 75 years (OR, 5.68; 95% CI, 2.87 to 11.23; p < 0.0001) emerged as predictors of elevated levels of d-dimer, and only NVAF (OR, 10.30; 95% CI, 5.67 to 18.72; p < 0.0001) emerged as a predictor of elevated levels of beta-TG.",
            "output": [
                "Is prothrombotic activity increased in patients with nonvalvular atrial fibrillation and risk factors for embolism?"
            ]
        },
        {
            "id": "task847-3d0571fb2ccd4b1aa747bc2134a16ec2",
            "input": "Recently, the authors identified molecular signatures and pathways associated with nonsmall cell lung carcinoma histology and lung development. They hypothesized that genetic classifiers of histology would provide insight into lung tumorigenesis and would be associated with clinical outcome when evaluated in a broader set of specimens.', 'Associations between patient survival and immunostaining for 11 representative histologic classifiers (epidermal growth factor receptor [EGFR], CDK4, syndecan-1, singed-like, TTF-1, keratin 5, HDAC2, docking protein 1, integrin alpha3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens.', 'Sixty-three tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixty-three percent of tumors were clinical Stage I lesions, and 37% were Stage II-III lesions. In a multivariate analysis that controlled for age, gender, and race, syndecan-1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18-0.87]; P < 0.05). Multivariate analysis also indicated that EGFR expression was associated with a significant reduced risk of death.",
            "output": [
                "Are expression of syndecan-1 and expression of epidermal growth factor receptor associated with survival in patients with nonsmall cell lung carcinoma?"
            ]
        },
        {
            "id": "task847-a88e6dd64bf3496f8e6f4d2fdffcfbd9",
            "input": "Regeneration and tolerance factor (RTF) has been recently suggested to contribute to the control of fetal-ablating immunity at the maternal-fetal interface through the induction of T helper 2 (Th2)-dominated response. The protein consists of a membrane-associated domain and an extracellular portion which is proteolitically cleaved to yield a soluble peptide. In humans, it has been shown to be expressed by invading cytotrophoblasts and decidual lymphoid cells, to be increased on peripheral blood B lymphocytes during a normal gestation and on circulating natural killer cells during unsuccessful pregnancies. However, the expression of RTF in other cell types and, specifically, in non-hematopoietic maternal cells of the human uterus has not been characterized in detail. Thus, we have specifically studied the expression and modulation of the cytokine in human endometrium obtained in different phases of the cycle and in early pregnancy.', 'The 20 kDa extracellular domain of RTF has been localized by immunohistochemical method and Western blot analysis. Levels of RTF messenger RNA (mRNA) in basal and stimulated conditions have been evaluated by semiquantitative reverse transcription-polymerase chain reaction.', 'The extracellular domain of RTF could be detected in both the glandular epithelium and stroma with diffuse distribution in both cycling endometrium and first trimester decidua. Both cycling and pregnant endometrium expressed the gene for RTF but mRNA levels resulted significantly increased in secretory phase-endometrial stromal cells when compared to proliferative phase samples. Inflammatory cytokines, interleukin-1beta and tumour necrosis factor alpha were able to directly increase endometrial RTF mRNA expression.",
            "output": [
                "Is the placental immunomodulatory cytokine regeneration and tolerance factor also expressed by both human cycling and early pregnant endometrium?"
            ]
        },
        {
            "id": "task847-eba8a3189c27457bb979f442e20e3ac6",
            "input": "High sodium intake is implicated in contributing to progression of chronic renal failure. We studied the effect of high sodium consumption on progression of rat experimental renal failure while sodium-induced hypertension was pharmacologically controlled.', '64 Sprague-Dawley rats underwent 5/6 nephrectomy. Subsequently, they were divided in three groups which were fed either low, normal, or high sodium diet. Only the high sodium-consuming group developed hypertension. This group was further divided in two subgroups in which hypertension was either untreated or titrated to normotension by hydralazine alone or with propranolol.', 'Sequential GFR values did not differ between the respective normotensive groups. Survival downslopes of all three normotensive groups (including the pharmacologically treated, high sodium-consuming subgroup) were also similar, extending over 10 weeks. By contrast, pharmacologically untreated animals exhibited severe hypertension and 100% mortality within 3 weeks. In all experimental groups, 24-hour urinary sodium excretion paralleled sodium intake. Proteinuria rose similarly and significantly in all animals on high sodium. A significant correlation between 24-hour sodium and proteinuria was evident throughout the experimental period.",
            "output": [
                "Does hypertension but not sodium intake determine progression of renal failure in experimentally uremic rats?"
            ]
        },
        {
            "id": "task847-2c15e87c8d6647fa92dfdc9ceb7d41b8",
            "input": "The American College of Obstetricians and Gynecologists (ACOG) revised its practice bulletin on vaginal birth after Cesarean (VBAC) in October 1998 and July 1999 to require the presence of a surgeon, anesthesiologist and operating personnel throughout the trial of labor for patients with prior Cesarean. This study measures the change in VBAC rates from 1998 to 2001 and examines possible reasons for this change.', 'We examined birth certificate and hospital data in the State of Maine from 1998 to 2001. Hospital-specific rates for primary Cesareans, total Cesareans, repeat Cesareans and vaginal deliveries after previous Cesarean were obtained. Additionally, we surveyed current obstetric-care providers in Maine regarding reasons for change in VBAC rates at their institutions.', \"VBAC rates declined by over 50% from 30.1 to 13.1%. The total Cesarean rate climbed from 19.4 to 24.0%. The most commonly reported reason for decrease in VBAC varied depending on whether a practitioner's hospital met ACOG guidelines.",
            "output": [
                "Are vaginal birth after Cesarean rates declining rapidly in the rural state of Maine?"
            ]
        },
        {
            "id": "task847-785a9dcc6ef44ffa8dbbf9c1dcfcdff3",
            "input": "Work stress is associated with an increased risk for cardiovascular disease (CVD). Exaggerated cardiovascular reactivity to work-related stressors or incomplete recovery after work is a proposed mechanism underlying this increase in risk. This study examined the effects of work stress on 24-hour profiles of the pre-ejection period (PEP), a measure of cardiac sympathetic activity, obtained from ambulatory measurement of the impedance cardiogram.', \"A total of 67 male white-collar workers (age 47.1 +/- 5.2) underwent ambulatory monitoring on 2 workdays and 1 non-workday. Work stress was defined according to Siegrist's model as 1) a combination of high effort and low reward at work (high imbalance) or 2) an exhaustive work-related coping style (high overcommitment).\", 'High overcommitment was associated with shorter absolute PEP levels during all periods on all 3 measurement days, reduced wake-to-sleep PEP differences and reduced PEP variability, as indexed by the SD.",
            "output": [
                "Is overcommitment to work associated with changes in cardiac sympathetic regulation?"
            ]
        },
        {
            "id": "task847-80dc013bc1c2430aa2a6ead5f5dd6816",
            "input": "With the advent of ambulatory blood pressure monitoring has come the awareness that blood pressure (BP) normally drops, or \"dips,\" at night by roughly 10%. A number of pathological conditions have been associated with the nondipping of nocturnal BP. In general, researchers have looked at dipping in neurological and cardiovascular disorders. We examined the extent to which nocturnal nondipping might be influenced by relatively gross measures of social environment.', 'This study examined 78 healthy adults and adults with mild hypertension who were not currently receiving medication, aged 25 to 52 years (mean age = 38.2). Forty-two participants self-identified as black and 36 identified as white.', 'Age, body mass index, apnea-hypopnea index, screening BP, ethnicity, and socioeconomic status (SES) were significantly associated with nocturnal BP dipping, accounting for 41% of the variance in dipping (F[6,51] = 5.473, p <.001). When SES was entered on the last step of a hierarchical regression analysis, it independently accounted for 8% of the variance in dipping, even after accounting for ethnicity, such that the lower the SES, the more the nondipping.",
            "output": [
                "Is socioeconomic status associated with nocturnal blood pressure dipping?"
            ]
        },
        {
            "id": "task847-1b462752a85d4860b9351dc0c12239ea",
            "input": "Optimistic people report a higher quality of life, engage in more active coping and adopt more health-promoting behaviors than people low in optimism, ie, pessimism. We evaluated whether pessimists are more likely to show progression in carotid disease than optimists.', 'A total of 209 middle-aged healthy premenopausal women enrolled in an epidemiological study of cardiovascular risk factors and had carotid scans 10.4 years and 13.5 years later when they were at least 5 years postmenopausal. Women completed the Life Orientation Test (LOT), a measure of pessimistic and optimistic attitudes, at study entry and at the time of the first carotid scan. Analyses evaluated the association of LOT scores and change in carotid intima medial thickness (IMT) across 3 years.', 'Multiple linear regression analyses showed that the higher the pessimism scores at study entry, the greater the increase in mean IMT (beta = 0.17, p <.007). A comparison of those in the lowest quartile of LOT scores (most optimistic) with those in the other three quartiles showed that the most optimistic group had less progression than the remaining more pessimistic women (mean percent increase = 1.3 and 6.0 for mean IMT, F = 15.4, p <.001). Women who were chronically optimistic at study entry and at the first carotid scan (bottom quartiles at both times) had less progression in mean IMT than did those who were chronically pessimistic (top quartiles at both times).",
            "output": [
                "Do optimistic attitudes protect against progression of carotid atherosclerosis in healthy middle-aged women?"
            ]
        },
        {
            "id": "task847-6e6a68ed9ce244bb946b90f853cc9536",
            "input": "The aim of this study was to visualize early stage prostate cancer (Cap) in a clinical setting. In previous studies, the results of magnetic resonance imaging (MRI) for screening Cap have rarely been confirmed by well-designed multisite prostate biopsy.', 'The prostate glands of 90 men with elevated prostate-specific antigen (PSA) were imaged by dynamic contrast-enhanced MRI (DCE-MRI) before transrectal ultrasound-guided 14-cores prostate biopsy. Each core was divided into three subcore fractions (total of 42 fractions) to generate a histological localization diagram, which was compared with localization-visualized DCE-MRI.', \"The detection rate of Cap in 57 patients with PSA < 10.0 ng/ml was 36.8% as determined by the initial biopsy. DCE-MRI uncovered 92.9% of the clinically significant Caps and its specificity was 96.2% for the first biopsy session. One case with positive DCE-MRI and a negative primary biopsy was positive with additional biopsies. All of 26 DCE-MRI positive cases had significant Cap, and two of eight patients with histological Cap and negative or equivocal imaging had significant cancer. In total, 9 of 20 cases with DCE-MRI stage T2 underwent radical prostatectomy. All of them had organ-confined disease, although 33-77% (mean 63%) of them were expected to be rated T3 or higher by Partin's table.",
            "output": [
                "Is dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) a useful modality for the precise detection and staging of early prostate cancer?"
            ]
        },
        {
            "id": "task847-021dde224e584b2a8601ba2fb88c6166",
            "input": "Body weight correlates with risk of breast cancer death.', 'A retrospective cohort study using patient medical records, electronic cancer registry data, and archived tissue specimens.', 'A 395-bed, comprehensive community hospital.', 'One thousand three hundred seventy-six women, aged 24 to 81 years, who were diagnosed with breast cancer between January 1, 1988, and December 31, 1995, and for whom complete medical records and adequate tissue specimens existed.', \"Body weight at the time of diagnosis and patient status (ie, alive and free of breast cancer, living with breast cancer, dead of breast cancer, or dead of other cause) at the time of longest follow-up. Additional data collected, including age at diagnosis, menopausal status, tumor size, tumor grade, lymph node status, stage at diagnosis, race, estrogen-receptor (ER) status, and treatment information, were used to create multivariate Cox proportional hazards models to estimate hazard rate (HR) ratios and 95% confidence intervals (CIs) for breast cancer death. We collected ER status from the patients' medical records, when available, and supplemented the information by using immunohistochemical techniques to determine ER status from archived paraffin-embedded tumor blocks.\", 'Patients were followed up for a median of 6.8 years after diagnosis. Two hundred forty-six patients died from breast cancer. Among patients with early-stage disease (I and IIA), we observed a dose-response relationship of increasing weight with increasing likelihood of dying of breast cancer. Compared with women in the lowest category of weight (< 133 lb [60 kg] at diagnosis), women in the highest category (> or = 175 lb [79 kg]) experienced a 2.5-fold increased risk of dying from breast cancer (HR ratio, 2.54 [95% CI, 1.08-6.00]; trend P = .02). Women with ER-negative cancer experienced an approximately 2-fold higher risk of dying from breast cancer compared with women with ER-positive cancer, regardless of stage at diagnosis. Women in the upper 50th percentile of weight with early-stage disease and with ER-negative tumors had a nearly 5-fold increased risk of dying (HR ratio, 4.99 [95% CI, 2.17-11.48]; P for interaction = .10) compared with women in the lower 50th percentile of weight and ER-positive tumors. The results were similar for body mass index, a measure of obesity in which weight is adjusted for height.",
            "output": [
                "Does body weight correlate with mortality in early-stage breast cancer?"
            ]
        },
        {
            "id": "task847-f360737150334ea29ad1c606b19e51f6",
            "input": "Obesity is associated with increased morbidity and mortality in critically injured blunt trauma patients.', 'Case-control study of all critically injured blunt trauma patients between January 2002 and December 2002.', 'Academic level I trauma center at a county referral hospital.', 'Two hundred forty-two consecutive patients admitted to the intensive care unit following blunt trauma. Patients were divided into 2 groups by body mass index. The obese group was defined as having a body mass index of 30 kg/m2 or higher, and the nonobese group was defined as having a body mass index lower than 30 kg/m2.', 'Univariate and multivariate analyses were performed to identify risk factors for mortality. Complications and length of stay were also evaluated.', 'Of the 242 patients, 63 (26%) were obese, and 179 (74%) were nonobese. The obese and nonobese groups were similar with regard to age (mean +/- SD, 49 +/- 18 years vs 45 +/- 22 years), male sex (63% vs 72%), Glasgow Coma Scale score (mean +/- SD, 11 +/- 5 vs 11 +/- 5), and injury severity score (mean +/- SD, 21 +/- 13 vs 20 +/- 14). The obese group had a higher body mass index (mean +/- SD, 35 +/- 7 vs 24 +/- 3; P<.001). Mechanisms of injury and injury patterns were similar between groups. The obese group had a higher incidence of multiple organ failure (13% vs 3%; P =.02) and mortality (32% vs 16%; P=.008). Obesity was an independent predictor of mortality with an adjusted odds ratio of 5.7 (95% confidence interval, 1.9-19.6; P=.003).",
            "output": [
                "Is obesity an independent risk factor of mortality in severely injured blunt trauma patients?"
            ]
        },
        {
            "id": "task847-db31841d91fe4a85ade62c36cc814858",
            "input": "In the presented study the effect of age and cytogenetics on clinical outcome in acute myeloid leukemia (AML) was evaluated. The 1225 patients with de novo AML were separated according to age as follows: A1: 16 to 49 years (n=442), A2: 50 to 59 years (n=246), A3: 60-69 years (n=333), A4: 70 years and older (n=204).', 'Patients were categorized with respect to cytogenetics into 5 groups: C1: t(15;17) (n=107), C2: CBF-AML/inv(16)/t(8;21) (n=171), C3: 11q23/MLL (n=42), C4: complex aberrant karyotype (n=130), C5: other: normal, other abnormalities, 5q-/-5, 7q-/-7, inv(3)/t(3;3), other 3q abnormalities (n=746). For each age category univariate cox regression analysis was performed using age as a continuous variable and C1 to C5 as dichotomous variables.', 'In cohort A1 all parameters were significantly associated with overall survival (OS). However, in multivariate analysis all cytogenetic parameters were independently correlated with OS, while age was not. In cohort A2 only CBF and complex aberrant karyotype were significantly correlated with OS. In A3 t(15;17), complex karyotype and age, and in A4 only complex karyotype and age were significantly associated with OS in univariate and multivariate analyses. Within all cytogenetic subgroups except AML 11q23/MLL there were significant associations between age and OS.",
            "output": [
                "Does the influence of age on prognosis of de novo acute myeloid leukemia differ according to cytogenetic subgroups?"
            ]
        },
        {
            "id": "task847-cbdf4ca69ebc4f5ca6263143a4d586f0",
            "input": "Inflammatory processes are an integral component of the initiation, progression, and destabilization of atherosclerotic lesions. Tumor necrosis factor-alpha (TNF-alpha) is considered a primary mediator of inflammatory processes.', 'The role of TNF-alpha in plaque progression and plaque destabilization was investigated in the innominate arteries of older TNF-alpha receptor p55 deficient mice that were generated on a hyperlipidemic apolipoprotein E deficient background (p55-/- apoE-/-). There were no significant differences in levels of circulating cytokines, plaque progression, plaque composition or features of plaque destabilization in p55-/- apoE-/- compared to wild type (p55+/+ apoE-/-) mice.",
            "output": [
                "Are lesion progression and plaque composition altered in older apoE-/- mice lacking tumor necrosis factor-alpha receptor p55?"
            ]
        },
        {
            "id": "task847-1d7e65248fd0496789ef5cfc09be9601",
            "input": "To examine the relationships among dietary quality, weight status, and human immunodeficiency virus (HIV) infection in US adolescents and young adults.', 'This cross-sectional study was embedded in the Reaching for Excellence in Adolescent Care and Health cohort study of HIV-infected and HIV-uninfected, at-risk youth. Biochemical, clinical, and sociodemographic data were available. Dietary intake was collected using the Block Food Frequency Questionnaire and a modified Healthy Eating Index was calculated to measure diet quality.', 'Participants included 264 HIV-infected and 127 HIV-uninfected youth 13 to 23 years old (75.2% women, 67.3% African American/non-Hispanic, 20.5% Hispanic, 12.3% other) at 14 clinic sites.', 'Determinants of obesity and the modified Healthy Eating Index were tested using logistic and generalized linear regression.', 'About half (51.7%) of participants were overweight or obese. Obesity was positively associated with being a woman, living independently, watching television >or=3 hours per day, previous dieting, and being from the northeastern or southern United States. Youth who were HIV uninfected or HIV infected with CD4 + T cells >or=500 cells/microL had similar obesity rates; overweight (25%) and obesity (20%) was prevalent among women even with CD4 + T cells <200 cells/microL. The modified Healthy Eating Index score was 56.2+/-0.6, reflecting a diet needing improvement. HIV infection, watching television >or=3 hours/day, and being from the Chicago, IL, area were associated with a lower-quality diet.",
            "output": [
                "Are hIV-infected US youth at high risk of obesity and poor diet quality : a challenge for improving short- and long-term health outcomes?"
            ]
        },
        {
            "id": "task847-38566f97b43c4130b70297a5e3f6833c",
            "input": "Prostasomes are secretory granules produced, stored, and released, by the glandular epithelial cells of the prostate. They express the glycosylphosphatidylinositol (GPI)-anchored complement regulatory protein CD59, which has been shown to be transferred to spermatozoa and erythrocytes.', 'The CD59 content of prostasomes isolated from seminal fluid and malignant prostate cells (PC-3, DU145, and LNCaP) and the transfer of prostasomal CD59 to rabbit erythrocytes (RE) and to PIPLC-treated and unmanipulated cancer cells were investigated using FACS. All prostasomes were also incubated with RE and tested in a hemolytic assay.', 'Prostasomes from cancer cells had higher expression of CD59 than those of normal cells. Prostasomal CD59 of different origin could be transferred to RE, malignant cell lines stripped of CD59 by PIPLC, or unmanipulated LNCaP cells. Malignant cell prostasomes had an increased ability to inhibit complement-mediated lysis compared to those from non-malignant cells.",
            "output": [
                "Does transfer of functional prostasomal CD59 of metastatic prostatic cancer cell origin protect cells against complement attack?"
            ]
        },
        {
            "id": "task847-27b4824f14ec44559a5823b11a2ee27f",
            "input": "To assess the prognostic value of SYT-SSX fusion type, in comparison with other factors, in a population of 165 patients with synovial sarcoma (SS).', 'Data on 165 patients with SS (141 with localized disease at diagnosis) were studied retrospectively. The following parameters were examined for their potential prognostic value: age at diagnosis, sex, tumor site (extremities v proximal/truncal), size, histology, mitotic count, necrosis, histologic grade (Federation Nationale des Centres de Lutte Contre le Cancer system), stage (1997 tumor-node-metastasis system classification), surgical margin status (assessed histologically), and fusion type (SYT-SSX1 v SYT-SSX2). Median follow-up time was 37 months (range, 2 to 302 months).', 'Among those patients with localized disease at diagnosis, median and 5-year disease-specific survivals (DSS) for the SYT-SSX1 and SYT-SSX2 subgroups were 126 months and 67.4% versus 82 months and 63.2%, respectively (P = .12). Median and 5-year metastasis-free survivals (MFS) were 84 months and 54.2% for SYT-SSX1 versus 50 months and 47.6% for SYT-SSX2 (P = .76). Univariate analyses showed that high histologic grade (grade 3), high mitotic count (>/= 10 mitoses/10 high-power fields), stage III disease, size greater than 7 cm, tumor necrosis, and presence of areas of poorly differentiated morphology were significant adverse prognostic factors for DSS and MFS, whereas SYT-SSX fusion type, tumor histology (biphasic v monophasic), and patient sex were not. Age greater than 35 years adversely affected DSS but not MFS. In multivariate analyses, histologic grade was the most significant prognostic factor for both DSS and MFS.",
            "output": [
                "Is histologic grade , but not SYT-SSX fusion type , an important prognostic factor in patients with synovial sarcoma : a multicenter , retrospective analysis?"
            ]
        },
        {
            "id": "task847-54e1ffa6612e40ffa3a031f45d2f141a",
            "input": "Although marked repolarisation abnormalities (MRAs) are considered innocuous in trained athletes, their functional significance awaits clarification. The aim of this study was to further evaluate the pathophysiological implications of such MRAs.', 'We compared left ventricular (LV) functional response to exhausting exercise in 39 male athletes with (n=22) or without (n=17) MRAs and with no structural cardiac abnormalities, by means of a portable radionuclide monitoring system (Vest, Capintec, Inc., Ramsey, NJ). MRAs were defined by the presence of negative T waves > or =2 mm in three or more rest ECG leads. The Vest data were averaged for 30 s and analysed at baseline and at different heart rate (HR) values (50%, 75%, 85%, 95% and 100% of peak HR), as well as at 2, 5 and 10 min of recovery.', 'There were no significant differences in the effect of exhausting exercise between athletes with and athletes without MRAs. However, there was a significant difference in the trend in end-diastolic volume (EDV) during exercise depending upon the group of athletes considered (p=0.05). EDV differed significantly between the two groups of athletes at peak HR (p=0.031). EDV in athletes with MRAs was lower than that in athletes without MRAs (102%+/-7% vs 107%+/-8%, p=0.034).",
            "output": [
                "Is left ventricular end-diastolic volume decreased at maximal exercise in athletes with marked repolarisation abnormalities : a continuous radionuclide monitoring study?"
            ]
        },
        {
            "id": "task847-d5d0330ff02e46a7b339aa950b4c7e20",
            "input": "In several malignant tissues, the angiopoietins are principal regulators of vascular growth and regression, but in normal prostate and prostate tumors the role of the angiopoietins is unknown.', 'Angiopoietin (ang) 1 and 2 were immunolocalized in TUR-diagnosed prostate tumors with long follow-up and the expression was related to vascular density and clinicopathological variables.', 'Ang 1 was strongly expressed in the basal epithelial cell layer in non-malignant tissue, whereas tumors had lower levels localized to the epithelial cells. A weak ang 2 immunoreaction was observed in non-malignant tissue and in low to intermediate Gleason score (GS) tumors, with a similar expression pattern. However, most high GS tumors showed an intense ang 2 staining. Ang 2 was significantly correlated to GS, density of endoglin stained blood vessels, metastases, and to cancer specific survival.",
            "output": [
                "Is angiopoietin 2 expression related to histological grade , vascular density , metastases , and outcome in prostate cancer?"
            ]
        },
        {
            "id": "task847-da2f530807074423a2e58a27f59041b4",
            "input": "To determine the role of P and its nuclear receptor PR in the growth of ectopic uterine tissue of mice with or without a disrupted PR gene.', 'Animal study.', 'Academic medical center.', 'Female wild-type (WT) and transgenic knockout mice for P receptor (PRKO).', 'Endometriosis was induced in the following groups of ovariectomized adult mice: [1] untreated WT, [2] estradiol (E(2))-treated WT, [3] P-treated WT, [4] E(2) + P-treated WT, [5] untreated PRKO, [6] E(2)-treated PRKO, and [7] E(2) + P-treated PRKO (n = 5 in each group).', 'The size of ectopic uterine tissue in WT and PRKO mice were compared between the groups subjected to treatments with P or E(2). Tissue proliferating cell nuclear antigen (PCNA) levels were compared among these groups.', 'Treatment with P only significantly decreased the size of WT ectopic uterine tissue. The untreated PRKO ectopic uterine tissue was significantly larger than WT tissue. Estradiol increased the size of ectopic uterine tissues, and this E(2)-dependent growth could be suppressed by P in WT tissues but not in PRKO tissues. Finally, the hormone-dependent changes in ectopic uterine tissue size were accompanied by comparable alterations in PCNA levels.",
            "output": [
                "Are intact progesterone receptors essential to counteract the proliferative effect of estradiol in a genetically engineered mouse model of endometriosis?"
            ]
        },
        {
            "id": "task847-096e6d68521643619ff125352fd87c04",
            "input": "Activating mutations of FLT3 have been identified in multiple myeloid malignancies. Two types of activating mutations have been described: (1) the internal tandem duplication (FLT3-ITD) and (2) point mutations within the activating loop (FLT3-ALM). Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative disorder of early childhood. Mutations and other genetic abnormalities of RAS, NF1, and PTPN11 have been implicated as causative events in JMML, but approximately 25% of JMML patients harbor none of these abnormalities. We investigated whether FLT3 mutations might also contribute to JMML pathogenesis, and if present, whether FLT3 status would correlate with disease natural history and prognosis.', 'Genomic DNA was isolated from peripheral blood and bone marrow samples of 60 patients meeting international JMML diagnostic criteria. Samples were analyzed for FLT3-ITD and FLT3-ALM using polymerase chain reaction and restriction endonuclease digestion.', 'FLT3-ALM was found in 1/60 (1.7%) patients analyzed. Direct sequencing confirmed a C836G mutation. Clinical and laboratory characteristics of the JMML patient with the FLT3-ALM did not differ from the remainder of the cohort. No FLT3-ITD mutations were detected.",
            "output": [
                "Are activating FLT3 mutations rare in children with juvenile myelomonocytic leukemia?"
            ]
        },
        {
            "id": "task847-3db3cdb67ac543fb9d302304a691c2b2",
            "input": "To assess the ability of endobronchial ultrasonography (EBUS) using a guide sheath (EBUS-GS) to diagnose peripheral pulmonary lesions.', 'We devised a technique for EBUS-GS covering a miniature probe, and 150 lesions were evaluated in a prospective open study. In this procedure, the probe covered by a guide sheath is introduced into the lesion via the working channel of a bronchoscope. The probe is withdrawn, while the guide sheath is left in situ. A brush or biopsy forceps is introduced through the guide sheath into the lesion.', 'One hundred sixteen of 150 EBUS-GS procedures (77%) were diagnostic. Cases in which the probe was located within the lesion had a significantly higher diagnostic yield (105 of 121 cases, 87%) than when the probe was located adjacent to it (8 of 19 cases, 42%) [p < 0.0001, chi(2)]. The diagnostic yield from EBUS-GS in lesions </= 10 mm (16 of 21 lesions, 76%), >10 to </= 15 mm (19 of 25 lesions, 76%; p = 0.99, chi(2)), >15 to </= 20 mm (23 of 35 lesions, 66%; p = 0.41, chi(2)), and > 20 to </= 30 mm (33 of 43 lesions, 77%; p = 0.96, chi(2)) were similar, demonstrating the efficacy of EBUS-GS even in lesions </= 10 mm in diameter. In 54 of 81 lesions </= 20 mm, fluoroscopy was not able to confirm whether the forceps reached the lesion. However, the yield was the same with (67%, 18 of 27 lesions) and without (74%, 40 of 54 lesions) successful fluoroscopy (p = 0.96, chi(2)). Moderate bleeding occurred in two patients (1%); there were no other complications.",
            "output": [
                "Does endobronchial ultrasonography using a guide sheath increase the ability to diagnose peripheral pulmonary lesions endoscopically?"
            ]
        },
        {
            "id": "task847-e27a92ba41b94387b6fe8e007a6ff982",
            "input": "Histone deacetylase (HDAC) inhibitors have shown significant anti-proliferative and apoptotic properties on various cancer cells, including prostate cancer, and are therefore being evaluated as treatment modalities. However, the specific effect of HDAC inhibitors on androgen-sensitive and androgen-independent cell lines have not been thoroughly studied which we hypothesized could be different. We therefore assessed whether three structurally unrelated HDAC inhibitors, trichostatin A (TSA), depsipeptide (FR901228), and sodium butyrate, affect cell death in the prostate cancer cell lines LNCaP, DU-145, and PC-3.', 'To investigate the extent and the nature of cell death, we used Trypan blue exclusion assay, phase-contrast light microscopy, fluorescence microscopy, and Western blot analyses.', 'At concentrations where they potentiate transcriptional activation, all three HDAC inhibitors induced cell death in LNCaP and DU-145 cells, but not in PC-3 cells, within the timeline of the experiments. HDAC inhibitor-induced cell death in LNCaP and DU-145 cells showed several characteristic apoptotic features, such as cell shrinkage, nuclear condensation, and poly(ADP) ribose polymerase cleavage. However, there were differences in the way LNCaP and DU-145 cells responded to treatment with various HDAC inhibitors. For example, whereas TSA and FR901228 were more effective in inducing apoptosis in LNCaP cells compared with DU-145 cells, the reverse was true for sodium butyrate. Moreover, within the same cell line, TSA, FR901228, and sodium butyrate exhibited different potencies for induction of apoptosis.",
            "output": [
                "Do histone deacetylase inhibitors differentially mediate apoptosis in prostate cancer cells?"
            ]
        },
        {
            "id": "task847-c6582a7021b248cdab9c7edcd6f2e686",
            "input": "Neuroendocrine (NE) differentiation in prostate tumors has been correlated with androgen independent disease and increased risk of death. In vitro, IL-6 initiates NE differentiation utilizing the signal transduction initiated by the interaction with IL-6R alpha and gp130. In this study we analysed the NE differentiation process in vitro and in vivo using the LNCaP androgen dependent cell line via ligand independent induction of NE differentiation.', 'LNCaP cells were transfected with a constitutively active gp130 subunit, gp130act. Cell proliferation rate was determined and clones were examined for neuroendocrine differentiation by morphological change, upregulation of CgA and serotonin and formation of dense core vesicles with LNCaP parental cells as the control. Xenograft formation was examined and compared in immunocompromised mice.', 'Gp130act expression promoted significant neuroendocrine differentiation in vitro as determined by a NE like morphology change (increased neurite like extension formation), elevated CgA expression and the formation of dense core vesicles (DCV). These measures concurred with those examined in LNCaP cells following 100 ng/ml IL-6 treatment. Further investigation of the LNCaP gp130act cells in vivo, in immunocompromised androgen intact mice, confirmed that the NE like morphology, as determined by histological and high resolution transmission electron microscopy, was maintained.",
            "output": [
                "Does constitutive activation of gp130 lead to neuroendocrine differentiation in vitro and in vivo?"
            ]
        },
        {
            "id": "task847-15302938a295486aaca082582ea044a3",
            "input": "Androgen-independent prostate cancer is today an incurable disease, but increased understanding of the mechanisms for the transition into an androgen-independent state may increase the possibilities for more efficient strategies in the future.', 'An androgen-independent subline, LNCaP-19, to the androgen-dependent prostate cancer cell line LNCaP was developed in vitro under standard culture conditions. The characteristics of LNCaP-19 regarding androgen responsiveness, PSA, and VEGF secretion was studied in vitro. The growth in vivo and the microvessel density (MVD) of the tumors were studied after inoculation in nude mice.', 'LNCaP-19 grows equally well in dextran-charcoal stripped FBS (DCC-FBS) as in normal FBS, and rapidly gives rise to tumors in both intact and castrated mice, indicating a true androgen-independent growth. The PSA secretion from LNCaP-19 cells was lower than from LNCaP cells, while the VEGF level was comparable to the secretion from LNCaP cells without androgen stimulation. The MVD was increased in the LNCaP-19 tumors, and the vessels also displayed a changed morphology with exclusively small microvessels without lumen.",
            "output": [
                "Is transition of an androgen-dependent human prostate cancer cell line into an androgen-independent subline associated with increased angiogenesis?"
            ]
        },
        {
            "id": "task847-402754fc100a4d388b8fd522c28db6f0",
            "input": "This study was undertaken to assess the presence and degree of anxiety and depression in a group of UK patients with primary Sj\u00f6gren's syndrome (1 degrees SS).\", 'Cross-sectional.', 'Department of Oral Medicine, Liverpool University Dental Hospital.', 'Eighty adult patients; 40 diagnosed with 1 degrees SS according to the revised European Criteria and 40 age/gender-matched controls with no history of chronic illness.', 'Hospital Anxiety and Depression Scale (HADS), a self-administered questionnaire designed to evaluate the presence and degree of anxiety and depression in a clinical setting.', 'Age, gender, Hospital Anxiety and Depression Scale (HADS).', \"Forty patients with 1degrees SS and 40/age/gender-matched controls completed the HADS. Scores for anxiety in both the 1 degrees SS and control groups showed no statistically significant difference. Patients with 1 degrees SS had statistically significant higher, mean HADS scores for depression than the controls. There was an increased prevalence of 'definite' clinical depression in the 1 degrees SS group.",
            "output": [
                "Are uK patients with primary Sj\u00f6gren 's syndrome at increased risk from clinical depression?"
            ]
        },
        {
            "id": "task847-9d1634fdc0794f1dabe818ee42f0af47",
            "input": "To examine the impact of a unique evidence-based clinical pathway on six outcomes of care in patients hospitalized for community-acquired pneumonia (CAP).', 'A retrospective cohort study of CAP patients discharged between January 1999 and December 2001, from 31 Adventist Health System institutions nationwide. A total of 22,196 records were available for multivariate analyses. Odds ratios (OR) for the outcomes were calculated and stratified by a unique severity score. The severity score ranged from 1 to 5, where 5 indicated the most severe condition.', 'Pathway patients were significantly less likely to die in-hospital compared with non-pathway patients in four of the five severity strata (OR in severity level 1=0.37; 95% confidence interval [CI], 0.20-0.70). In all severity strata, pathway patients were approximately twice as likely as non-pathway patients to receive blood cultures and appropriate antibiotic therapy. Among patients who were classified as severity level 1, pathway patients experienced an 80% reduction in the odds of respiratory failure requiring mechanical ventilation (OR=0.20; 95% CI, 0.12-0.33).",
            "output": [
                "Does clinical pathway care improve outcomes among patients hospitalized for community-acquired pneumonia?"
            ]
        },
        {
            "id": "task847-92affd5f994c476aa2c2486696b1d154",
            "input": "The vascular endothelial growth factor (VEGF) family and VEGF receptors (VEGFR) play an essential role in the angiogenesis of both pathologic and nonpathologic conditions. However, the prognostic significance of VEGF and VEGFR expression in ovarian carcinoma is unclear.', 'The tissue expression levels of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 in 80 specimens of ovarian carcinoma were examined immnohistochemically. The results obtained were analyzed clinicopathologically.', 'VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 were expressed both in tumor cells and in adjacent endothelial cells of blood and lymph vessels. The tissue expressions of VEGF-C and VEGFR-2 were correlated significantly with tumor extension, including peritoneal metastases outside the pelvic cavity (P = 0.0010 and P = 0.0008, respectively), lymph node metastases (P = 0.0030 and P = 0.0018, respectively), and positive ascitic cytology (P = 0.025 and P = 0.0016, respectively). Conversely, there was no significant correlation between VEGF-A and VEGFR-3 expression and clinicopathologic features of ovarian carcinoma. Logistic regression analysis revealed that the expressions of VEGF-C and VEGFR-2 also were independent risk factors for peritoneal and lymph node metastases. Survival curves determined by the Kaplan-Meier method and in univariate analysis demonstrated that high expression levels of VEGF-C and VEGFR-2 were associated with the 5-year survival rate. In multivariate analysis, high expression levels of VEGF-C and VEGFR-2 emerged as independent indicators for disease-specific survival.",
            "output": [
                "Are vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 related closely to the prognosis of patients with ovarian carcinoma?"
            ]
        },
        {
            "id": "task847-54c41c70590c46678f7401c01c4106f7",
            "input": "Degradation of the extracellular matrix by malignant tumor cells has an essential role in the process of tumor invasion and metastasis. The 2 gelatinolytic matrix metalloproteinases (MMPs) MMP-2 and MMP-9 are believed to be key enzymes in this process. We investigated the possible relationship between in situ gelatinolytic activity of MMPs and clinicopathological factors in patients with bladder cancer to clarify whether these proteins would be critical for tumor advancement in this disease.', 'We evaluated the intensity of gelatinolytic activity in 25 bladder cancer tissues by film in situ zymography (FIZ). To clarify the MMP(s) responsible for gelatinolytic activity in bladder cancer tissues we examined MMP-2 and MMP-9 expression in bladder tissues by gelatin zymography. MMP expression was also confirmed by reverse transcriptase-polymerase chain reaction and Western blotting. We then investigated the association between MMP expression detected by gelatin zymography and the intensity of gelatinolytic activity determined by FIZ.', 'FIZ demonstrated that all tumor tissues had in situ gelatinolytic activities. There was a statistically significant correlation between the intensity of gelatinolytic activity, and tumor grade, stage, vessel invasion and cause specific survival (p <0.05). Stronger in situ gelatinolytic patterns were documented in cases with higher pro and active MMP-2 expression.",
            "output": [
                "Does in situ gelatinolytic activity correlate with tumor progression and prognosis in patients with bladder cancer?"
            ]
        },
        {
            "id": "task847-2c242c89ec1648d8960a49113deceb53",
            "input": "Bacillus Calmette-Guerin (BCG) binds to the tumor cell as a result of mycobacterial receptors for fibronectin (FN). Cell surface bound FN serves as a bridge through which BCG attaches to the tumor cell. Despite the importance of FN studies have demonstrated an idiosyncratic decrease in BCG adherence in response to exogenous FN. We evaluated the effect of exogenous and autocrine FN on the ability of BCG to adhere to the tumor cell surface and initiate cellular signaling.', 'BCG adherence to parental 253J and FN over expressing 253JTGFbeta1-8 cells as well as to the intrinsic FN expressing cell line 647V was quantified using green fluorescent protein-BCG. Experiments were performed to assess the effect of FN on BCG initiated signal transduction through nuclear factor kappaB and AP1. Finally, the integrity of the BCG activated signaling pathway in transforming growth factor-beta1/FN over expressors was assessed using antibody mediated cross-linking of the FN receptor.', 'BCG adherence was decreased in cell lines with high autocrine expression of FN. Exogenous FN prevented BCG induced transactivation of nuclear factor kappaB and AP1 reporter constructs. No BCG stimulated signaling to these reporters could be detected in FN over expressing 253J cells. NonFN dependent alpha5beta1 cross-linking initiated signal transduction in FN over expressing cells.",
            "output": [
                "Does autocrine over expression of fibronectin by human transitional carcinoma cells impair bacillus Calmette-Guerin adherence and signaling?"
            ]
        },
        {
            "id": "task847-f9812d0da5e44f92b5db12b03b36df56",
            "input": "We assessed the feasibility of a novel urinary test for prostate cancer based on the presence of alpha methylacyl coenzyme A racemase (AMACR) protein in voided urine specimens obtained after prostate biopsy.', 'Clean catch voided urine specimens were prospectively collected from 26 consecutive men immediately after transrectal ultrasound guided prostate biopsy for suspected malignancy. The presence of AMACR was evaluated in a blinded manner by Western blot analysis and correlated with biopsy results and patient clinical information.', 'AMACR was detected in the urine in 18 of 26 patients (69%). AMACR was detected in all 12 patients with biopsy confirmed adenocarcinoma of the prostate (100% sensitivity, 95% CI 75 to 100), in 5 of 12 with no evidence of cancer on biopsy (58% specificity, 95% CI 29 to 78) and in 1 of 2 (50%, 95% CI 3 to 80) with atypia on biopsy. Overall AMACR detection was associated with cancer status by prostate biopsy in 21 of 26 patients (86%).",
            "output": [
                "Do prostate cancer detection on urinalysis for alpha methylacyl coenzyme a racemase protein?"
            ]
        },
        {
            "id": "task847-5a76d4a2221a448c97498a4008b7446d",
            "input": "Although up to 30% of men who undergo radical prostatectomy for clinically organ-confined prostate cancer will relapse with disseminated disease, currently it is not possible to predict these patients.', 'Androgen receptor (AR) immunoreactivity in stromal and epithelial compartments of tumor foci was evaluated by video image analysis in 53 radical prostatectomy specimens. Kaplan-Meier and Cox Regression analyses were used to determine whether AR immunostaining was related to rate and risk of relapse, respectively.', 'Ninety-eight percent (52/53) of the tumors contained AR positive malignant epithelial cells. Kaplan-Meier analysis indicated that patients with high AR levels (>64% AR positive nuclear area) in the malignant epithelial cells or low AR levels (<or=45% AR positive nuclear area) in the peritumoral stroma cells, were more likely to relapse earlier following radical prostatectomy. The shortest time to relapse and the highest relapse rate was for patients with both high AR in the malignant epithelial cells and low AR in the peritumoral stromal cells.",
            "output": [
                "Do androgen receptor levels in prostate cancer epithelial and peritumoral stromal cells identify non-organ confined disease?"
            ]
        },
        {
            "id": "task847-3b4799d5a4424e4ebca4f903a5287bb0",
            "input": "Melatonin, the main secretory product of the pineal gland, inhibits the growth of several types of cancer cells. Melatonin limits human prostate cancer cell growth by a mechanism which involves the regulation of androgen receptor function but it is not clear whether other mechanisms may also be involved.', 'Time-course and dose-dependent studies were performed using androgen-dependent (LNCaP) and independent (PC3) prostate cancer cells. Cell number, cell viability, and cell cycle progression were studied. Neuroendocrine differentiation of these cells was evaluated by studying morphological and biochemical markers. Finally, molecular mechanisms including the participation of melatonin membrane receptors, intracellular cAMP levels, and the PKA signal transduction pathway were also analyzed.', 'Melatonin treatment dramatically reduced the number of prostate cancer cells and stopped cell cycle progression in both LNCaP and PC3 cells. In addition, it induced cellular differentiation as indicated by obvious morphological changes and neuroendocrine biochemical parameters. The role of melatonin in cellular proliferation and differentiation of prostate cancer cells is not mediated by its membrane receptors nor related to PKA activation.",
            "output": [
                "Does melatonin reduce prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism?"
            ]
        },
        {
            "id": "task847-614fd216c71a4d6a9ccc8a3e78895aa8",
            "input": "Staphylococcus aureus (S. aureus) is a common, normal pathogenic flora that colonizes mucosal tissues. We previously reported that glomerulonephritis occurs during methicillin-resistant S. aureus infection, and demonstrated polyclonal elevation of serum immunoglobulin A (IgA) and IgG levels and various histological findings, such as mesangial extracapillary and endocapillary proliferation. To investigate the pathogenic roles of S. aureus antigens, we induced IgA-type glomerulonephritis in mice by immunization with antigens derived from S. aureus, as a model of human IgA nephropathy (IgAN).', \"Balb/c mice (Th2 dominant type) and C57BL/6 mice (Th1 dominant type) were immunized biweekly for 4 months with antigens derived from S. aureus mixed with Freund's incomplete adjuvant.\", 'Mesangial proliferative glomerulonephritis with IgA, IgG and complement 3 (C3) depositions were observed in all Balb/c mice. Although C3 depositions and cell proliferation in the mesangial area were also seen in C57BL/6 mice, they were not correlated with urinary findings. In Balb/c mice, S. aureus antigens were detected in glomeruli using affinity-purified human anti-S. aureus antibodies, but there was no staining in C57BL/6 mice. The antibodies reacted with several S. aureus antigens, based on Western blot analysis, and the main 30-35 kDa band differed in intensity in Balb/c and C57BL/6 mice. In addition, increased transforming growth factor beta (TGF-beta) messenger RNA (mRNA) expression was seen in Balb/c mice compared to C57BL/6 mice.",
            "output": [
                "Do staphylococcus aureus antigens induce IgA-type glomerulonephritis in Balb/c mice?"
            ]
        },
        {
            "id": "task847-8e1ecc19594e4c7191d4ce8ffd9948b7",
            "input": "Tyrphostin AGL-2043 is a potent tricyclic quinoxaline inhibitor of PDGF beta-receptor tyrosine kinase (PTK), Kit, and Flt3. We have shown previously that selective inhibition of PDGF beta-receptor PTK by tyrphostins markedly reduces SMC proliferation and migration in vitro, reduces neointima formation in balloon-injured porcine femoral arteries, and reduces neointimal stenosis in stented porcine coronary arteries when administered intramurally within biodegradable nanoparticles. The present study was designed to determine the effect of AGL-2043 delivered from a stent-based, biodegradable polymeric coating on neointima formation in the porcine coronary artery model.', 'Stents coated with biodegradable, polylactic/glycolic acid (PLGA) polymer, with (n=13) or without (n=11) 180 mcg AGL-2043 were implanted into the proximal LAD of 24 Sinclair mini-pigs (34+/-4 kg) to achieve a 1.1:1 stent/artery diameter ratio. The delivery of drug from stent to tissue was confirmed by high-performance liquid chromatography. After 28 days, histomorphometric analysis showed that in-stent stenosis in animals treated with AGL-2043 was reduced by 50% (51+/-21% versus 26+/-10%, p=0.001), the absolute neointimal area was reduced by 44% (2.38+/-1.04 versus 1.31+/-0.43 mm(2), p=0.004), and the absolute luminal area was increased by 57% (2.19+/-1.09 versus 3.39+/-0.59 mm(2), p=0.003). There were no significant differences between control and AGL-2043 in injury score (1.24+/-0.11 vs. 1.15+/-0.12, p=0.07) or inflammation score (1.19+/-0.35 vs. 1.07+/-0.33, p=0.41). Moreover, the difference in % in-stent stenosis between control and treated animals remained highly significant even after normalizing the % stenosis to the degree of injury (p=0.0008) or to the inflammation score (p=0.001). Mortality for this study was zero. Tissue concentration in segments 1 cm proximal and distal to the stents, were negligible or zero at 1 h, 24 h, and 4 weeks after stent implantation.",
            "output": [
                "Does tyrphostin AGL-2043 eluting stent reduce neointima formation in porcine coronary arteries?"
            ]
        },
        {
            "id": "task847-e119ae76ac0341b89da07a00a50f807f",
            "input": "Anxiety and depression are common features of coeliac disease. Depression is cause of non-compliance to treatment in chronic illness.', 'To evaluate the useful of psychological support counselling to improve affective disorders and gluten-free diet adherence in coeliac disease with anxiety and depression.', 'A total of 66 coeliac disease patients with state anxiety and current depression were enrolled. Patients were randomized in two groups: in group A psychological support was started at the beginning of gluten-free diet, while group B was free of psychological support. Both groups were followed every 2 weeks for 6 months. State and Trait Anxiety Inventory test Y-1 and the modified Zung self-rating depression scale were administered before (T0) and after 6 months of gluten-free diet (T1).', 'At T1 no difference was found between groups in the percentage of state anxiety, while a significant lower percentage of depressed subjects was found in group A with respect to group B (15.1% vs. 78.8%; P=0.001). In the follow-up period, a significant lower compliance to gluten-free diet was found in group B with respect to group A (39.4% vs. 9.1%; P=0.02).",
            "output": [
                "Does psychological support counselling improve gluten-free diet compliance in coeliac patients with affective disorders?"
            ]
        },
        {
            "id": "task847-25077465decd43f9a958104ab8a7e951",
            "input": "The role of Helicobacter pylori in gastro-oesophageal reflux disease (GERD) is controversial.', 'To compare the severity of GERD in infected vs. non-infected patients, as part of an ongoing randomized controlled trial that examines the impact of H. pylori eradication on GERD-related outcomes.', 'Consecutive GERD patients underwent urea breath testing and completed validated GERD symptom severity, and quality of life questionnaires as well as, 24-h pH-metry. These parameters, as well as demographics and endoscopic findings were assessed in double-blinded fashion and compared between H. pylori-infected and non-infected subjects.', \"Helicobacter pylori-infected GERD patients (n=50) were significantly older and less educated than non-infected patients (n=51). They also used proton pump inhibitors less often but had no difference in symptoms (as measured with both the Spechler's Activity Index and the Gastrointestinal Symptom Rating Scale), quality of life, endoscopic findings or 24-h pH-metry findings.",
            "output": [
                "Is there no difference in the disease severity of gastro-oesophageal reflux disease between patients infected and not infected with Helicobacter pylori?"
            ]
        },
        {
            "id": "task847-7786c41a51dc421e817bcdf48acf678a",
            "input": "Hemin, the oxidized form of heme, accumulates in intracranial hematomas and is a potent oxidant. Growing evidence suggests that it contributes to delayed injury to surrounding tissue, and that this process is affected by the heme oxygenase enzymes. In a prior study, heme oxygenase-2 gene deletion increased the vulnerability of cultured cortical astrocytes to hemin. The present study tested the effect of HO-2 gene deletion on protein oxidation, reactive oxygen species formation, and cell viability after mixed cortical neuron/astrocyte cultures were incubated with neurotoxic concentrations of hemin.', 'Continuous exposure of wild-type cultures to 1-10 microM hemin for 14 h produced concentration-dependent neuronal death, as detected by both LDH release and fluorescence intensity after propidium iodide staining, with an EC50 of 1-2 microM; astrocytes were not injured by these low hemin concentrations. Cell death was consistently reduced by at least 60% in knockout cultures. Exposure to hemin for 4 hours, a time point that preceded cell lysis, increased protein oxidation in wild-type cultures, as detected by staining of immunoblots for protein carbonyl groups. At 10 microM hemin, carbonylation was increased 2.3-fold compared with control sister cultures subjected to medium exchanges only; this effect was reduced by about two-thirds in knockout cultures. Cellular reactive oxygen species, detected by fluorescence intensity after dihydrorhodamine 123 (DHR) staining, was markedly increased by hemin in wild-type cultures and was localized to neuronal cell bodies and processes. In contrast, DHR fluorescence intensity in knockout cultures did not differ from that of sham-washed controls. Neuronal death in wild-type cultures was almost completely prevented by the lipid-soluble iron chelator phenanthroline; deferoxamine had a weaker but significant effect.",
            "output": [
                "Does heme oxygenase-2 gene deletion attenuate oxidative stress in neurons exposed to extracellular hemin?"
            ]
        },
        {
            "id": "task847-eac3cd932ead47dcb41f1ff92a547e0a",
            "input": "To reach and grasp an object in space on the basis of its image cast on the retina requires different coordinate transformations that take into account gaze and limb positioning. Eye position in the orbit influences the image's conversion from retinotopic (eye-centered) coordinates to an egocentric frame necessary for guiding action. Neuroimaging studies have revealed eye position-dependent activity in extrastriate visual, parietal and frontal areas that is along the visuo-motor pathway. At the earliest vision stage, the role of the primary visual area (V1) in this process remains unclear. We used an experimental design based on pattern-onset visual evoked potentials (VEP) recordings to study the effect of eye position on V1 activity in humans.\", 'We showed that the amplitude of the initial C1 component of VEP, acknowledged to originate in V1, was modulated by the eye position. We also established that putative spontaneous small saccades related to eccentric fixation, as well as retinal disparity cannot explain the effects of changing C1 amplitude of VEP in the present study.",
            "output": [
                "Are early visual evoked potentials modulated by eye position in humans induced by whole body rotations?"
            ]
        },
        {
            "id": "task847-86618c8b53e34b9a81ef47369f20833f",
            "input": "Tibial bones are shorter and less resistant to shear forces after treatment with doxorubicin, methotrexate, or cisplatin. We investigated the pattern of failure after shear loading of the proximal tibial growth plate in rats treated with these chemotherapeutic agents.', 'Male Wistar rats from the age of 4 weeks were given doxorubicin intravenously at 15 mg/m2 body surface area (BSA), methotrexate 60 mg/m2 BSA, or cisplatin 7.5 mg/m2 BSA. There was one nontreated control group fed ad libitum an d a diet control group for each drug-treated group. At the age of 13 weeks the tibial bones were dissected. The proximal growth plate was shear loaded to failure in the posteroanterior direction. The pattern of failure through the growth plate was examined.', 'In rats fed ad libitum the failure pattern ran mainly through the transitional zone between proliferating and hypertrophic chondrocytes, but the pattern of failure showed considerable variability. The pattern in rats treated with methotrexate or cisplatin and that in their diet controls were comparable. In rats treated with doxorubicin the fracture ran mainly through the trabecular zone.",
            "output": [
                "Does chemotherapy affect the pattern of failure after shear loading of the proximal tibial growth plate?"
            ]
        },
        {
            "id": "task847-24f9d6837bcc4659bb8de71045e21de6",
            "input": "The objective of the ICF Core Sets project is the development of internationally agreed Brief ICF Core Sets and Comprehensive ICF Core Sets.', 'The methods to develop both ICF Core Sets, the Comprehensive ICF Core Set and the Brief ICF Core Set, involved a formal decision-making and consensus process integrating evidence gathered from preliminary studies and expert opinion.', 'The results regarding the development of the ICF Core Sets for 12 health conditions (chronic widespread pain, low back pain, osteoarthritis, osteoporosis, rheumatoid arthritis, chronic ischemic heart disease, diabetes mellitus, obesity, obstructive pulmonary diseases, breast cancer, depression, and stroke) are presented in this supplement.",
            "output": [
                "Does development of ICF Core set for patients with chronic conditions?"
            ]
        },
        {
            "id": "task847-8180d87418a248ecbf8ea151a1a18ac0",
            "input": "Human protectin (CD59) is a regulator of complement activation that inhibits complement-mediated cell lysis, and thus might confer immune resistance to tumor cells. CD59 expression has been described in a variety of human malignancies, including breast cancer. Since a comprehensive investigation of CD59 expression in prostate cancer has not been conducted yet, we aimed to determine the significance of CD59 expression in prostate cancer.', 'Eighty-six primary adenocarcinomas of the prostate were immunostained using a monoclonal CD59 antibody (clone MEM-43) and a standard detection system. The immunoreactivity of the tumor was evaluated as low versus high for statistical analysis. Additionally, CD59 mRNA levels were determined by real-time PCR in matched (tumor/normal) microdissected tissues from 26 cases.', 'Cytoplasmic CD59 immunoreactivity was found in epithelia of prostate cancer, prostatic intraepithelial neoplasia, benign hyperplasia, atrophic, and normal glands. High rates of CD59 expression were noted in 36% of prostate cancer cases and were significantly associated with tumor pT stage (P = 0.043), Gleason grade (P = 0.013) and earlier biochemical (PSA) relapse in Kaplan-Meier analysis (P = 0.0013). On RNA level, we found an upregulation in 19.2% (five cases), although the general rate of CD59 transcript was significantly lower in tumor tissue (P = 0.03).",
            "output": [
                "Does increased CD59 protein expression predict a PSA relapse in patients after radical prostatectomy?"
            ]
        },
        {
            "id": "task847-eba36041508c4f5785549e7603e881f2",
            "input": "Cancer-protective effects of isoflavones like genistin or genistein are well known. High intakes and an adequate absorption rate of isoflavones are necessary for efficient chemoprevention, though other dietary agents might increase absorption efficacy. The aim of this study was to investigate the effect of phloridzin, an inhibitor of the sodium-dependent glucose transporter (SGLT1), on genistin absorption and metabolism.', 'Phloridzin and genistin were luminally administered in an isolated preparation of luminally and vascularly perfused rat small intestine. A synthetic perfusate free from blood components was used as vascular medium, with a perfluorocarbon as oxygen carrier. Luminal media consisted of a bicarbonate buffered sodium chloride solution spiked with genistin (24.5 micromol/l) and phloridzin (1 mmol/l).', 'In previous experiments, genistin absorption rate of 17.2% has been observed. In the present study, phloridzin administered simultaneously with genistin, increased genistin uptake 2.5 fold (44.5%).",
            "output": [
                "Does phloridzin improve absorption of genistin in isolated rat small intestine?"
            ]
        },
        {
            "id": "task847-65ab18953851438397640e605851f09c",
            "input": "The metabolic response to surgery includes a net loss of proteins that influences negatively the clinical evolution of the patients. We investigated the effect of perioperative nutrition on protein metabolism alterations immediately after surgery.', 'A control group of 21 surgery patients were submitted to conventional perioperative nutritional protocol (18 h of fasting plus low-dose glucose after surgery). An experimental group of eight similar patients was given complete parenteral nutrition during 24 h before and 24 h after surgery. Nitrogen balance, whole body protein synthesis, breakdown, and 3-methylhistidine were determined before surgery and 24 h after surgery.', 'The immediate response to surgery with conventional nutritional management was a net protein loss (-1.023 g prot. kg(-1) day(-1)), caused by an increase in the protein breakdown (137.9% of preoperative values), while the protein synthesis remained unchanged (98.4%). The 3-methylhistidine excretion was not increased in respect to perioperative values, suggesting that the degraded protein was not from muscular origin. The experimental group with perioperative nutrition showed neither protein loss (+0.075 g prot. kg(-1) day(-1)) nor changes in protein synthesis or breakdown vs. preoperative values (96.3% and 88.0%, respectively).",
            "output": [
                "Does perioperative nutrition prevent the early protein losses in patients submitted to gastrointestinal surgery?"
            ]
        },
        {
            "id": "task847-7251d778311b4242b29de144226725c1",
            "input": "Dementia is a chronic illness associated with a progressive loss of cognitive and intellectual abilities, such as memory, judgment and abstract thinking. The objective of this study was to assess the health utilities of patients with dementia in Europe and identify the key factors influencing their Health-Related Quality of Life (HRQol).', \"This study used cross-sectional data from the Odense study; a Danish cohort of patients aged 65-84 living in Odense, Denmark. A total of 244 patients with mild to severe dementia were interviewed together with a caregiver about their health status and activities of daily living (ADL). Alzheimer's disease was diagnosed according to the NINCDS-ADRDA criteria for probable dementia. Vascular dementia and other types of dementia were diagnosed according to the DSM-IIIR criteria. Severity of dementia was defined by score intervals on the Mini Mental State Examination score: mild (MMSE 20-30), moderate (MMSE 10-19), and severe (MMSE 0-9). Based on the ADL information, the patients' dependency level was defined as either dependent or independent. Questions from the Odense Study were mapped into each of the five dimensions of the EQ-5D in order to assess patients' HRQol. Danish EQ-5D social tariffs were used to value patients' HRQol.A regression analysis of EQ-5D values was conducted with backward selection on gender, age, severity, ADL level and setting in order to determine the main factor influencing HRQoL.\", 'The EQ-5D weight in patients independent upon others in ADL was 0.641 (95% CI: [0.612-0.669]), and in those dependent upon others was 0.343 (95% CI: [0.251-0.436]).",
            "output": [
                "Is ability to perform activities of daily living the main factor affecting quality of life in patients with dementia?"
            ]
        },
        {
            "id": "task847-6fa8a6b98e5b4d76b496ba55b62eca40",
            "input": "Cyclin-dependent kinases (CDKs) are a large family of proteins that function in a variety of key regulatory pathways in eukaryotic cells, including control over the cell cycle and gene transcription. Among the most important and broadly studied of these roles is reversible phosphorylation of the C-terminal domain (CTD) of RNA polymerase II, part of a complex array of CTD/protein interactions that coordinate the RNAP II transcription cycle. The RNAP CTD is strongly conserved in some groups of eukaryotes, but highly degenerate or absent in others; the reasons for these differences in stabilizing selection on CTD structure are not clear. Given the importance of reversible phosphorylation for CTD-based transcription, the distribution and evolutionary history of CDKs may be a key to understanding differences in constraints on CTD structure; however, the origins and evolutionary relationships of CTD kinases have not been investigated thoroughly. Moreover, although the functions of most CDKs are reasonably well studied in mammals and yeasts, very little is known from most other eukaryotes.', 'Here we identify 123 CDK family members from animals, plants, yeasts, and four protists from which genome sequences have been completed, and 10 additional CDKs from incomplete genome sequences of organisms with known CTD sequences. Comparative genomic and phylogenetic analyses suggest that cell-cycle CDKs are present in all organisms sampled in this study. In contrast, no clear orthologs of transcription-related CDKs are identified in the most putatively ancestral eukaryotes, Trypanosoma or Giardia. Kinases involved in CTD phosphorylation, CDK7, CDK8 and CDK9, all are recovered as well-supported and distinct orthologous families, but their relationships to each other and other CDKs are not well-resolved. Significantly, clear orthologs of CDK7 and CDK8 are restricted to only those organisms belonging to groups in which the RNAP II CTD is strongly conserved.",
            "output": [
                "Do comparative genomics of cyclin-dependent kinases suggest co-evolution of the RNAP II C-terminal domain and CTD-directed CDKs?"
            ]
        },
        {
            "id": "task847-f50c8113df144bc1bad7a5ef1af62822",
            "input": "The mitogen-activated protein kinases (MAPKs) have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2) has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P) state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6), were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE) binding (CREB) protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined.', 'A single 15 min session of forced swimming increased P-Erk2 levels 2-3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3) were increased in all brain regions about 2-5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively) were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to approximately 300-fold). Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex) areas.",
            "output": [
                "Do activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions?"
            ]
        },
        {
            "id": "task847-7e0d830722b840beaf9bfa68cf15a167",
            "input": "Fibroblast growth factors (FGFs) and their receptors (FGFRs) expedite stromal-epithelial communication in development and homeostasis of the human prostate. Loss of resident epithelial cell FGFR2IIIb that responds to stromal FGF7 and FGF10 accompanies malignant progression of both model animal and human prostate tumors.', 'We examined whether restoration of FGFR2IIIb by transfection in the malignant human prostate tumor PC-3 cell line restored cellular properties associated with less malignant tumors. Cell proliferation, apoptosis, and tumor cell implants were used to monitor malignant properties. Activity of FGFR2IIIb was assessed by immunoblot of FRS2 and p44/42 MAP kinase. Immunochemical analysis of pancytokeratin and lactoferrin expression was utilized to assess changes in cellular differentiation.', 'Expression of FGFR2IIIb in PC-3 cells by transfection resulted in growth suppression in vitro and reduced tumor formation in vivo concurrent with increased cellular differentiation and apoptosis.",
            "output": [
                "Does restoration of fibroblast growth factor receptor2 suppress growth and tumorigenicity of malignant human prostate carcinoma PC-3 cells?"
            ]
        },
        {
            "id": "task847-0377e74610c04c07bc428c061d4bf148",
            "input": "This study was conducted to estimate the incidence and clinical predictors of post-thoracotomy shoulder pain and to determine the effectiveness of thoracic epidural block in alleviating this pain.', 'A prospective clinical trial.', 'University teaching hospital.', \"Thirty-two adult patients undergoing elective thoracic surgery consented to participate in the study. All operations were open thoracotomies done by the same team of surgeons and anesthesiologists. A thoracic (T6) epidural catheter was placed before induction of general anesthesia. Each patient received 7 mL of lidocaine 2% epidurally and repeated doses of 5 mL of lidocaine 2% every half hour during the operation. Postoperatively, the occurrence of incision or ipsilateral shoulder pain was observed and treated with a maximal dose of 5 mL of lidocaine 2%. If ineffective, indomethacin suppository (nonsteroidal anti-inflammatory drug [NSAID]) was given. Variables such as patient's age, sex, American Society of Anesthesiologists physical status, type, site and duration of surgery, duration of anesthesia, the resection of main bronchus, and the use of thoracostomy tubes were recorded.\", 'Postoperatively, 10 patients (31%) had shoulder pain, 4 patients (12.5%) complained of incision pain, and 2 (6.3%) complained of both incision and shoulder pain. A bolus of 5 mL of lidocaine 2% in the epidural catheter relieved incision pain in all the patients, but was ineffective for shoulder pain. Indomethacin suppository was effective in these patients. No correlation was found between any variable and the occurrence of shoulder pain.",
            "output": [
                "Are thoracic epidural local anesthetics ineffective in alleviating post-thoracotomy ipsilateral shoulder pain?"
            ]
        },
        {
            "id": "task847-282914784db04741bf5026fff82b4bfb",
            "input": "To research the methods of purifying polyprenol from leaves of Ginkgo biloba L..', 'The purity of polyprenol was determined by HPLC to select the optimal purifying conditions.', 'The optimal conditions were degreased by 160 times of petroleum ether-ethyl acetate (9:1) firstly, then through a silica gel column (100-140 mesh) and eluted with petroleum etherethyl acetate (19:1).",
            "output": [
                "Does [ Studies on purification of polyprenol from Ginkgo biloba L. leave ]?"
            ]
        },
        {
            "id": "task847-9a41e716889b4516988acc42c7e348b7",
            "input": "The restoration of coronary flow after transient ischemia immediately induces life-threatening ventricular tachyarrhythmias. Although most of these arrhythmias disappear spontaneously, some of them induce serious hemodynamic changes. This retrospective study investigates the efficacy of therapy with intracoronary verapamil to terminate reperfusion-induced ventricular tachyarrhythmias in patients with acute myocardial infarction (AMI).', 'Between February 1992 and February 2003, 390 patients with a diagnosis of AMI were enrolled into the study. All patients received mechanical revascularization therapy within 6 h of onset of symptoms, and 109 patients experienced reperfusion-induced tachyarrhythmias. A subset of these patients was treated with intracoronary verapamil (0.25 to 1.0 mg) to terminate the reperfusion-induced tachyarrhythmia. They were evaluated for immediate termination of the tachyarrhythmias, hemodynamic changes, resumption rates, and major complications. Thirty-one patients (28%) were treated with intracoronary verapamil for the immediate termination of reperfusion-induced ventricular tachyarrhythmias. These tachyarrhythmias included 6 premature ventricular contractions, 19 accelerated idioventricular rhythms, 3 ventricular tachycardias, 2 ventricular fibrillations (VFs), and 1 torsades de pointes. Intracoronary verapamil was effective in rapidly terminating all reperfusion-induced arrhythmias except for VFs. The side effects of treatment included temporary hypotension (two patients) and bradycardia (one patient), although all patients recovered spontaneously. No major complications were induced by the intracoronary use of verapamil, and no resumptions of arrhythmias were documented.",
            "output": [
                "Does intracoronary verapamil rapidly terminate reperfusion tachyarrhythmias in acute myocardial infarction?"
            ]
        },
        {
            "id": "task847-d356ac8706f748148663684382128880",
            "input": "Data on combined coronary artery bypass grafting (CABG) and restrictive annuloplasty in patients with ischemic cardiomyopathy are scarce, and the effect on reverse left ventricular (LV) remodeling is unknown.', '51 patients with ischemic LV dysfunction (LV ejection fraction 31+/-8%) and severe mitral regurgitation (grade 3 to 4+) underwent CABG and restrictive annuloplasty with stringent downsizing of the mitral annulus (by 2 sizes, Physio-ring, mean size 28+/-2). Serial transthoracic echocardiographic studies were performed (before surgery and within 3 months and 1.5 years after surgery) to assess mitral regurgitation, transmitral gradient, leaflet coaptation, and left atrial and LV reverse remodeling. Clinical follow-up (New York Heart Association [NYHA] class, survival, events) was assessed at 2-year follow-up. Early operative mortality was 5.6%; at 2-year follow-up, all patients were free of endocarditis and thromboembolism, and 1 needed re-operation for recurrent mitral regurgitation; 2-year survival was 84%. NYHA class improved from 3.4+/-0.8 to 1.3+/-0.4 (P<0.01), with all patients in class I/II. Intraoperative transesophageal echo showed minimal (grade 1+) mitral regurgitation in 8 patients and none in 43, without stenosis. Leaflet coaptation was 0.8+/-0.2 cm. These values remained unchanged; all patients had no or minimal (grade 1+) mitral regurgitation at 2-year follow-up. LV end-systolic and end-diastolic dimensions decreased from 51+/-10 to 43+/-12 mm (P<0.001) and from 64+/-8 to 58+/-11 mm (P<0.001). Left atrial dimension decreased from 53+/-8 to 47+/-7 mm (P<0.001).",
            "output": [
                "Does restrictive annuloplasty and coronary revascularization in ischemic mitral regurgitation result in reverse left ventricular remodeling?"
            ]
        },
        {
            "id": "task847-8d9fcd94240547aabe81acd5707809d1",
            "input": "Underlying left ventricular (LV) dysfunction contributes to poor survival after operation to correct ischemic mitral regurgitation (IMR). Many surgeons do not appreciate that a key component of the Bolling undersized mitral ring annuloplasty concept is to decrease LV wall stress by altering LV shape, but precise 3-dimensional (3-D) geometric data do not exist substantiating this effect. We tested the hypothesis that annular reduction decreases regional circumferential LV radius of curvature (ROC) in a model of acute IMR.', 'Eight adult sheep underwent insertion of an adjustable Paneth-type annuloplasty suture and radiopaque markers on the LV and mitral annulus. The animals were studied with biplane videofluoroscopy during baseline conditions, then before and after tightening the annuloplasty suture during proximal left circumflex occlusion. End-systolic circumferential regional LV ROC and mitral annular area were computed.', 'Acute IMR was eliminated (MR grade 2.1+/-0.4 to 0.4+/-0.4, mean+/-SD, P<0.05) by tightening the Paneth annuloplasty suture. Paneth suture tightening during circumflex occlusion also decreased end-systolic regional circumferential radii of curvature at the basal (anterior, 3.40+/-0.16 to 3.34+/-0.14 cm; posterior, 3.31+/-0.23 to 3.24+/-0.26 cm; P<0.05) and equatorial levels (anterior, 2.99+/-0.21 to 2.89+/-0.29 cm; posterior, 2.86+/-0.38 to 2.81+/-0.41 cm; P<0.05).",
            "output": [
                "Does undersized mitral annuloplasty alter left ventricular shape during acute ischemic mitral regurgitation?"
            ]
        },
        {
            "id": "task847-454e62f888d04337850195ecb730f92a",
            "input": "Role of P-selectin (CD62) and glycoprotein (GP) Ibalpha in posttransfusion clearance of platelet concentrates (PCs) is unclear.', 'Platelet (PLT) activation in vitro was determined by flow cytometry using anti-CD62 and anti-GPIbalpha. PC clearance in vivo was evaluated in an animal model using rabbits with an inhibited reticuloendothelial system, as measured by 0.5-hour (R(0.5)), 24-hour (R(24)), and total (R( summation operator )) PLT recoveries, and survival time (ST). Correlations were analyzed between in vitro assays of PLT activation and in vivo clearance of conventional (Days 2-5), outdated (Days 7-8), and refrigerated PCs.', 'Binding of anti-CD62 to the PLT surface was significantly increased and of anti-GPIbalpha decreased in outdated and refrigerated PCs compared to conventional PCs. Negative correlation was observed between in vitro anti-CD62 binding and the fast (R(0.5)) PLT clearance, but not with delayed (R(24) and ST) clearance. In contrast, anti-GPIbalpha binding showed positive correlations with delayed but not with fast PLT clearance. Overall (R( summation operator )) clearance correlated better with anti-GPIbalpha than with anti-CD62 binding. CD62 density on the PLT surface was decreased after PC transfusion, whereas GPIbalpha density remained unchanged.",
            "output": [
                "Does role of platelet surface glycoprotein Ibalpha and P-selectin in the clearance of transfused platelet concentrate?"
            ]
        },
        {
            "id": "task847-a671cff2cba84ff5a3df3a9260c36507",
            "input": "Biliary tract carcinoma is a deadly disease, accounting for nearly 4500 malignancy-related deaths each year in the United States. Early detection has the potential to improve survival for patients with biliary tract malignancies, enabling curative surgical resection. Early detection approaches would benefit from an accurate, minimally invasive diagnostic test. To identify novel diagnostic markers, the authors recently completed a comprehensive proteomic study of bile samples from patients with biliary carcinoma. One of the proteins identified by tandem mass spectrometry was Mac-2-binding protein (Mac-2BP). The authors evaluated the performance of Mac-2BP and its ligand, galectin-3, as diagnostic markers for patients with biliary carcinoma.', 'Levels of Mac-2BP, galectin-3, and CA19-9 were measured using an enzyme-linked immunosorbent assay (ELISA) in bile samples from patients with biliary tract carcinoma (n = 26), benign biliary conditions (n = 32), and primary sclerosing cholangitis (n = 20). Serum levels of Mac-2BP and galectin-3 also were determined using ELISA. Mac-2BP tissue expression was investigated by immunohistochemical methods using a biliary carcinoma tissue microarray.', 'Biliary Mac-2BP levels were elevated by a factor of approximately 3 in the biliary carcinoma group compared with the group of patients who had PSC or another type of nonneoplastic biliary disease. In contrast, Mac-2BP levels were not elevated in serum samples from patients with biliary carcinoma. According to the immunohistochemical analysis, Mac-2BP was expressed in 34 of 36 patients (94.4%) with biliary tract carcinoma. As a diagnostic marker for biliary carcinoma, Mac-2BP levels were as accurate as biliary CA19-9 levels, with an area under the curve (AUC) of 0.70 on receiver operator characteristic analysis. The use of both of these bile markers in combination, however, led to significantly better diagnostic accuracy compared with the accuracy achieved using CA19-9 alone (AUC, 0.75; P < 0.001). Serum and biliary galectin-3 levels did not differ in the biliary carcinoma group relative to the control groups.",
            "output": [
                "Is mac-2-binding protein a diagnostic marker for biliary tract carcinoma?"
            ]
        },
        {
            "id": "task847-1138e795cce34ff3bbe6e4199b3e23ad",
            "input": "Evidence of hyperplasia with atypia found both on random periareolar fine needle aspiration (RPFNA) and in nipple aspirate fluid (NAF) fluid are associated with an increased risk for breast cancer.', 'In this study, we report the correlation of NAF production with cytological assessment of ductal cells obtained by RPFNA.', '113 women at high risk for development of breast cancer attending the Breast Cancer Prevention Clinic at the University of Kansas Medical Center underwent a single NAF collection attempt and RPFNA.', 'NAF was successfully collected in 51% of women. There was no significant difference in age, 5-year Gail risk assessment, menopausal status, hormone use, family history of breast cancer, history of prior atypical hyperplasia/LCIS or history of contralateral DCIS/invasive breast cancer between women who produced NAF and those that did not. The only significant difference between the two groups was in history of prior lactation (p = 0.018). Twenty-seven of the 113 subjects were found to have hyperplasia with atypia by RPFNA was 31% in women who produced NAF versus 16% in those who did not (p = 0.07).",
            "output": [
                "Does failure of high risk women to produce nipple aspirate fluid exclude detection of cytologic atypia in random periareolar fine needle aspiration specimens?"
            ]
        },
        {
            "id": "task847-dff6f02e291740b2aebead1a1a6fa20f",
            "input": "The development of transplant coronary artery disease is associated with neovascularization in the thickened neointima. We previously reported that captopril inhibits neointimal proliferation in a rat allograft model. We postulated that angiogenic inducers are upregulated post-transplantation and captopril ameliorates transplant coronary artery disease by suppressing the angiogenic activity of coronaries.', 'Animals received no treatment or captopril (50 mg/kg/day). Allograft hearts were analyzed at post-transplantation Days 0, 14, and 21 and angiogenic inducer, plasma platelet-activating factor, determined. The conditioned media from coronaries and myocardium were tested for vascular endothelial growth factor, thrombospondin-1 and angiogenic activity using an endothelial migration assay and rat corneal neovascularization assay.', 'The captopril-treated group had reduced plasma platelet-activating factor and coronary media revealed earlier upregulation of thrombospondin-1 secretion, diminished vascular endothelial growth factor and no angiogenic activity. At Day 0, the coronary and myocardial conditioned medium had inhibitory activity due to thrombospondin-1, and circulating levels of platelet-activating factor were negligible. By 21 days post-transplantation, plasma platelet-activating factor was elevated and the conditioned medium from untreated coronaries had significantly higher angiogenic activity due to increased vascular endothelial growth factor whereas the myocardium remained non-angiogenic.",
            "output": [
                "Does captopril suppress post-transplantation angiogenic activity in rat allograft coronary vessels?"
            ]
        },
        {
            "id": "task847-4b9fc4ae683f49b9bb20a534b8fbda67",
            "input": "There is a paucity of data on the micronutrient status of low-income, lactating South African women and their infants under 6 months of age. The aim of this study was to elucidate the level of anaemia and vitamin A deficiency (VAD) in peri-urban breast-feeding women and their young infants.', 'Cross-sectional study including anthropometric, biochemical and infant feeding data.', 'Peri-urban settlement in Cape Town, South Africa.', 'Breast-feeding women (n=113) and their infants (aged 1-6 months) attending a peri-urban clinic.', 'Mean (standard deviation (SD)) haemoglobin (Hb) of the lactating mothers was 12.4 (1.3) g dl(-1), with 32% found to be anaemic (Hb<12 g dl(-1)). Maternal serum retinol was 49.8 (SD 13.3) microg dl(-1), with 4.5% VAD. Using breast milk, mean (SD) retinol concentration was found to be 70.6 (24.6) microg dl(-1) and 15.7 (8.3) microg/g milk fat, with 13% below the cut-off level of <8 microg/g fat. There was no correlation found between breast milk retinol and infant serum retinol. Z-scores (SD) of height-for-age, weight-for-age and weight-for-height were -0.69 (0.81), 0.89 (1.01) and 1.78 (0.83), respectively. Mean (SD) infant Hb was 10.9 (1.1) g dl(-1), with the prevalence of anaemia being 50%, 33% and 12% using Hb cut-offs below 11 g dl(-1), 10.5 g dl(-1) and 9.5 g dl(-1), respectively. Mean (SD) infant serum retinol was 26.9 (7.2) microg dl(-1), with 10% being VAD. None of the infants was exclusively breast-fed, 22% were predominantly breast-fed and 78% received complementary (mixed) breast-feeding. Thirty-two per cent of infants received weaning foods at an exceptionally young age (< or =1 month old).",
            "output": [
                "Are full-term , peri-urban South African infants under 6 months of age at risk for early-onset anaemia?"
            ]
        },
        {
            "id": "task847-f2a2d34bab194953af0e2c518131e412",
            "input": "Our aim was to investigate mechanisms of inflammation-induced endothelial dysfunction in humans.', 'Endothelial function in twenty-one healthy human volunteers was measured using forearm venous plethysmography before and 8 h after administration of typhoid vaccination to generate an inflammatory response. Basal and stimulated endothelial nitric oxide (NO) bioavailability was assessed by measurement of the responses to intra-arterial N(G)-monomethyl-l-arginine (l-NMMA) and bradykinin, respectively. The effects of supplementation with l-arginine or ascorbic acid were assessed to probe the effects of substrate deficiency and oxidative stress, respectively. Systemic effects were determined by measuring cytokine response, total anti-oxidant status (TAOS) and urinary protein excretion.', 'Vaccination induced a cytokine response, a fall in total anti-oxidant status and increased urinary albumin excretion (UAE). There was a reduction in the response to bradykinin (BK, P<0.005) and l-NMMA (P<0.0001) with no effect on the response to glyceryl trinitrate (GTN) and norepinephrine (NE). Following vaccination blood flow response to BK (but not GTN) was partially returned to pre-vaccine levels by infusion of ascorbic acid (P=0.01). Supplementation with l-arginine had no effect.",
            "output": [
                "Does inflammation-induced endothelial dysfunction involve reduced nitric oxide bioavailability and increased oxidant stress?"
            ]
        },
        {
            "id": "task847-8f3c28a265314de19c4b7e5766dac708",
            "input": "The purpose of this study was to investigate the contribution of inflammatory signaling containing tumor necrosis factor receptor-associated factor 6 (TRAF6) to neointimal formation in a balloon injury model of rabbit carotid artery.', 'Male Japanese white rabbits fed a normal diet were used. We transferred the dominant negative (DN) form of TRAF6 to a rabbit carotid artery that was subjected to balloon injury by in vivo electroporation method, and then evaluated its effect on intimal lesion formation after balloon injury.', 'An expression plasmid vector containing the TRAF6 DN sequence was successfully transferred to arterial wall cells, and its inhibitory effect on inflammatory signaling was confirmed by the marked suppression of nuclear factor-kappaB (NFkappaB) activity after injury. Morphometric analyses revealed significant inhibition of intimal lesion formation at 7 days after injury. Cell replication and accumulation of macrophages in the media were significantly decreased, and apoptosis was enhanced on day 2. Cell migration to the intima was suppressed on day 4. Extracellular signal-regulated kinase1/2 (ERK1/2) activity at 2 h after injury was also down-regulated. Interestingly, intimal cell replication was significantly blocked when TRAF6 DN was transfected at 7 days after injury.",
            "output": [
                "Does inflammatory signaling pathway containing TRAF6 contribute to neointimal formation via diverse mechanisms?"
            ]
        },
        {
            "id": "task847-4311a565addb489ba6b4919d6d507ee2",
            "input": "7-Ketocholesterol, a major oxysterol in oxidized low-density lipoproteins in advanced atherosclerotic plaques, induces vascular smooth muscle cell (SMC) death. We investigated whether cytochrome c release participated in SMC death induced by 7-ketocholesterol and whether the processes were reversible.', 'SMC cultures derived from the rabbit aorta were exposed to 25 microM 7-ketocholesterol. Cytochrome c and Bax were studied by means of immunofluorescence and immunoblotting, apoptosis by the TUNEL technique and mitochondrial structure by transmission electron microscopy.', '7-Ketocholesterol induced rapid upregulation of the proapoptotic protein Bax and its translocation from cytosol into the mitochondria (4 h). This was followed by mitochondrial cytochrome c release (65% at 8 h) into the cytosol, which was almost complete at 16 h. The mitochondria became spherical and ultracondensed, without showing signs of lysis. They clustered around the nucleus and were wrapped by wide cisternae of the rough endoplasmic reticulum. Cytochrome c release was not blocked by the pan-caspase inhibitor zVAD-fmk, in contrast to DNA fragmentation and SMC loss. Interestingly, upon removal of 7-ketocholesterol after 16 h and re-exposure to serum for 24 h, the mitochondrial cytochrome c content, their transmembrane potential and TUNEL labelling normalised and SMC loss decreased. However, none of these cell death markers was rescued when the SMCs had been exposed to the oxysterol for 24 h.",
            "output": [
                "Does 7-Ketocholesterol induce reversible cytochrome c release in smooth muscle cells in absence of mitochondrial swelling?"
            ]
        },
        {
            "id": "task847-af4560fddaf5428c80281dc02a370a67",
            "input": "Collagen plays a major role in arterial wall remodeling, aneurysm formation, and atherosclerotic cap stability. Smokers often have weakened arterial walls associating with aneurysm and thinned atherosclerotic plaque caps leading to rupture and acute coronary syndromes. We hypothesize that these detrimental effects on arterial wall by tobacco are partially mediated by disturbed collagen metabolism.', 'We first investigated the effect of cigarette smoke extracts (CSE) on prolyl-4-hydroxylase (P4H) expression and collagen production in human aortic endothelial cells (HAECs) and human coronary artery smooth muscle cells (HCSMCs). After exposure to 0.01-U CSE for 24 h, expression of P4Halpha-a rate limiting subunit of P4H enzyme responsible for the formation of 4-hydroxyproline in mature functional collagen, was significantly down-regulated according to Western blotting and quantitative RT-PCR (HAEC p < 0.01 and HCSMC p < 0.001) when treated by CSE. The decreased P4Halpha expression was corresponded with reduced cellular collagen levels (HAEC p < 0.001 and HCSMC p < 0.001). We also found that one of the cigarette components benzo(a)pyrene exerted similar effect as CSE, but not nicotine or acrolein. We further examined P4H expression in a few human atherosclerotic abdominal aortas. These in vivo data demonstrated that smokers had thinner atherosclerotic cap thickness and lower levels of P4Halpha and collagen.",
            "output": [
                "Does cigarette suppress the expression of P4Halpha and vascular collagen production?"
            ]
        },
        {
            "id": "task847-e04ffba6e57443fa8f50581f3d181a21",
            "input": "To determine if the timing of administration affects the dose of dolasetron necessary to prevent postoperative nausea and vomiting (PONV).', 'Pooled data from 8 randomized, multicenter, double-blind, placebo-controlled studies with common endpoints.', 'University hospital.', 'A total of 4,587 ASA physical status I, II, and III patients, including 4,124 females undergoing primarily gynecologic procedures and 463 males undergoing various procedures (i.e., thyroidectomy or orthopedic, ophthalmologic, urologic, ENT, or laparoscopic surgery).', 'Balanced general anesthesia was used during all procedures. Patients received a dose of dolasetron either for prevention of PONV (25 or 50 mg IV at induction; 25, 50, 100, or 200 mg orally 1 to 2 hours pre-induction; or 12.5, 25, 50, or 100 mg IV at end of anesthesia) or for treatment of PONV (12.5, 25, 50, or 100 mg IV). One PONV prevention study had an ondansetron (comparator) group.', 'Outcome measures over a 24-hour study period included complete response (defined as no vomiting/retching and no need for rescue medication), percentage of patients without nausea [defined as nausea visual analog scale (VAS) score < 5 mm], and maximum nausea according to VAS score.', 'A 12.5-mg IV dose of dolasetron resulted in a complete response rate that was statistically significantly higher than placebo and comparable to higher dolasetron doses (25 mg to 100 mg IV) when administered either near the end of anesthesia for prevention of PONV or at the onset of symptoms for treatment of PONV. In contrast, when administered at induction of anesthesia, a statistically significant treatment response was observed with dolasetron 50 mg IV, but not at a lower dose.",
            "output": [
                "Does timing of administration of dolasetron affect dose necessary to prevent postoperative nausea and vomiting?"
            ]
        },
        {
            "id": "task847-63d02def4fe34b0f9cd6301d501e2feb",
            "input": "To test the hypothesis that effective pulmonary capillary blood flow can be a useful indicator for estimating appropriate oxygenation and ventilation during one-lung ventilation in lung surgery.', 'Prospective data analysis.', 'A 770-bed general teaching hospital.', '15 ASA physical status II and III patients undergoing elective lung surgery.', 'Patients received general and thoracic epidural anesthesia and underwent lung operation with one-lung ventilation.', 'We measured effective pulmonary capillary blood flow by a partial CO2 rebreathing method and oxygenation parameters during two-lung ventilation before surgery, during one-lung ventilation, and during two-lung ventilation after lung surgery.', 'The effective pulmonary capillary blood flow index significantly decreased by 31.6%, which was associated with a significant decrease in arterial oxygen tension (PaO2). The pulmonary shunt fraction increased to 46.3% during one-lung ventilation. During two-lung ventilation, after chest closure, effective pulmonary capillary blood flow index divided by heart rate (i.e., effective pulmonary blood stroke flow index) was still significantly lower than that seen during two-lung ventilation before thoracotomy. There were significant correlations between effective pulmonary capillary blood flow, pulmonary blood stroke flow index, and PaO2.",
            "output": [
                "Is a noninvasive partial carbon dioxide rebreathing technique for measurement of pulmonary capillary blood flow also a useful oxygenation monitor during one-lung ventilation?"
            ]
        },
        {
            "id": "task847-f16f95eb7c1543d3bb0ce3edeb4fbb77",
            "input": "Corticosteroid treatment affects muscle protein and glutamine metabolism. In the present study we aimed to clarify to what extent anorexia, weight loss and corticosteroids determine protein and glutamine metabolism in muscle.', 'The study was performed in Wistar rats (300-350 g, n = 40) given triamcinolone (0.25 mg/kg/day i.m.) treatment (CS group) for 14 days, sham treated free fed (FF group), sham treated pair fed (PF group) and sham treated pair weight (PW group). In vivo protein and glutamine turnover were measured using L-[2,6-3H]phenylalanine and L-[3,4-3H]glurtamine as tracer in a three compartment model across the hindquarter.', 'Corticosteroid treatment decreased total body weight to a greater extent than can be explained by decreased food intake only, justifying the need for pair weight controls. Muscle weight loss was relatively greater in the corticosteroid treated rats than in the pair weight controls indicating specific corticosteroid induced changes in muscle protein metabolism. Pair weight rats increased muscle net protein breakdown rates from -5 +/- 3 nmol x 100 g body weight(-1) x min(-1) to -15 +/- 3 nmol x 100 g body weight(-1) x min(-1) (P < 0.05 vs FF). In the corticosteroid treated rats net protein breakdown rates increased to -22 +/- 4 nmol x 100 g body weight(-1) x min(-1) (P < 0.01 CS vs FF/PF) Net protein breakdown in corticosteroid treated rats was accompanied by increased glutamine efflux from the hindquarter (P < 0.05, CS vs FF/PF/PW). The latter could predominantly be explained by de novo synthesis. Furthermore, corticosteroid treatment induced a loss of plasma to free muscle glutamine gradient indicating down regulation of glutamine membrane transport rates into muscle. This effect was, however, similar in the pair weight control group and can thus be fully accounted for by the muscle weight loss.",
            "output": [
                "Is de novo glutamine synthesis induced by corticosteroids in vivo in rats secondary to weight loss?"
            ]
        },
        {
            "id": "task847-a5dc7eecc5fb4f738296740f96813608",
            "input": "Lichen sclerosus (LS) is a chronic inflammatory skin disease of unknown aetiology which can be associated with secondary malignancies. Recent evidence supports an autoimmune basis for this disorder, as demonstrated by autoantibodies to extracellular matrix protein 1 (ECM-1). The pathophysiological mechanisms leading to autoimmunity and carcinogenesis are poorly understood.', 'We hypothesized that oxidative stress, which has been demonstrated to be involved in the pathogenesis of several autoimmune and malignant disorders, contributes to these processes in LS.', \"Skin biopsies from 16 patients with untreated, histologically confirmed vulval LS were examined immunohistochemically using antibodies against the lipid peroxidation products malondialdehyde and 4-hydroxynonenale and against the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine. Protein carbonyls as markers of protein oxidation were visualized using the dinitrophenylhydrazone method. Expression of antioxidant enzymes was investigated. Normal vulval tissue from 16 subjects served as control.\", 'In vulval LS tissue a significant increase of lipid peroxidation products was found particularly within the basal cell layers of the epidermis, thus colocalizing with ECM-1. Oxidative DNA damage was detected throughout LS biopsies. Intriguingly, protein oxidation was significantly increased within the dermis of LS lesions, indicating oxidative protein damage in the areas of sclerosis and inflammation. The enzymatic antioxidant defence in LS was found to be significantly disturbed.",
            "output": [
                "Is oxidative stress implicated in the pathogenesis of lichen sclerosus?"
            ]
        },
        {
            "id": "task847-c8197e2388514cb2a8491be192ad8c8a",
            "input": "A psoriasis susceptibility locus on chromosome 16q was identified recently. This region coincides with a locus predisposing to Crohn's disease. Patients with Crohn's disease have a fivefold greater relative risk for development of psoriasis. In Crohn's disease mutation of the caspase recruitment domain family, member 15 (CARD15) gene (chromosome 16q12.1) confers susceptibility. In light of the overlap in linkage data, and the observation of comorbidity between Crohn's disease and psoriasis, it is plausible that both diseases share a common genetic factor.\", 'To assess the genetic contribution of CARD15 single nucleotide polymorphisms (SNPs) in the pathogenesis of type I psoriasis.', 'Eight SNPs in CARD15 were genotyped in 148 patients with type I psoriasis and 192 unrelated controls, following a test for population stratification. Genotype and allele frequencies were compared along with estimated SNP haplotype frequencies.', 'No differences were observed in genotype allele or haplotype frequencies between the case and control cohorts.",
            "output": [
                "Do cARD15/NOD2 single nucleotide polymorphisms confer susceptibility to type I psoriasis?"
            ]
        },
        {
            "id": "task847-98625b26bf1841cca18256967823d82d",
            "input": "Diffuse temporal lobe abnormalities can be observed on MRI of patients with mesial temporal lobe epilepsy (MTLE). Our objective was to perform qualitative and quantitative analyses of temporal lobe structures in patients with familial MTLE (FMTLE) and nonfamilial MTLE.', 'Two groups of patients were ascertained: 67 FMTLE patients (14 with refractory seizures) and 30 patients with nonfamilial refractory MTLE. We performed qualitative analyses of MRI (with multiplanar reconstruction) and volumes of hippocampi and anterior temporal lobes in all patients, and in a normal control group of 23 individuals. We used the Chi-square test and ANOVA for statistical analyses.', 'We identified anterior temporal lobe abnormalities by visual analysis in only 4% of FMTLE patients and atrophy of the anterior temporal lobe by volumetric analysis in 19%. In the group of nonfamilial MTLE patients we found anterior temporal lobe abnormalities by visual analysis in 17% of patients and anterior temporal lobe atrophy in 13%. Hippocampal atrophy was present in 90% of FMTLE and in 83% of nonfamilial MTLE. No signs of cortical dysplasia were observed.",
            "output": [
                "Are structural abnormalities similar in familial and nonfamilial mesial temporal lobe epilepsy?"
            ]
        },
        {
            "id": "task847-858b134c25b748ada94302d79a74e9d6",
            "input": "Frontotemporal dementia is a neurodegenerative disease affecting mostly the frontal and/or temporal lobes, with neuronal loss and intraneuronal and/or intraglial inclusions composed of hyperphosphorylated microtubule-associated protein tau and ubiquitin. Missense and splice site mutations in the TAU gene have been identified in approximately 15% of all frontotemporal dementia cases. In this study, we evaluated the involvement of mutations in the TAU gene in development of frontotemporal dementia phenotype in patients of French or English Canadian origins.', 'Fourteen patients with frontotemporal dementia phenotype and 98 normal controls were recruited for the study. The TAU gene was screened by sequencing and denaturing high performance liquid chromatography.', 'No mutations, except some new polymorphisms, were detected in the TAU gene of these patients. One polymorphism, however, may play a role in pathogenesis.",
            "output": [
                "Are tAU mutations a predominant cause of frontotemporal dementia in Canadian patients?"
            ]
        },
        {
            "id": "task847-7426695d16ea42e384db502b0f7e6f75",
            "input": "Single-cell gel electrophoresis, or the comet assay, a technique widely used for DNA damage analysis, has been used recently for detecting DNA fragmentation in cells undergoing apoptosis. However, the number of variants of this assay used thus far primarily detected the late stages of DNA fragmentation. Therefore, monitoring the progression of DNA fragmentation, which could greatly improve the analysis of cell death induction and progression at the single-cell level, has not been possible with this assay.', 'In the present study, a modification of the original neutral comet assay developed by Ostling and Johanson (Biochem Biophys Res Commun 123:291-298, 1984) was used to detect various stages of DNA fragmentation. This assay involves cell lysis with anionic detergents at nearly neutral pH (9.5) and does not include high salt concentration, unlike most other published methods. BMG-1 human glioma cells were induced to undergo programmed cell death by treating with a large dose (100 microM) of etoposide, and comets were prepared after different durations (1-24 h) of treatment.', 'In contrast to results of previously published studies, comets with different shapes reflecting progressive stages of DNA fragmentation were observed. Of these, six distinct shapes were identified and divided into three different categories based on the extent of fragmentation. Type A comets had a large head separated by a narrow \"neck\" region from an oval bulging tail that indicated initiation of fragmentation. Type B and C comets had a constantly diminishing head associated with a corresponding expansion of the tail and reflected intermediate and late stages of fragmentation, respectively. Type A and B comets appeared at a high frequency during early time points (1-6 h), whereas type C comets that indicated late stages of fragmentation were observed only after extended treatment (24 h). As a result, an elaborate kinetics of the progression of DNA fragmentation could be obtained.",
            "output": [
                "Does single-cell gel electrophoresis assay monitor precise kinetics of DNA fragmentation induced during programmed cell death?"
            ]
        },
        {
            "id": "task847-b6e85afe265a46deba993510163c46ed",
            "input": "Aldosterone blockade has followed in the footsteps of ACE inhibition in reducing mortality in patients with heart failure. This is associated with its beneficial effects on endothelial function and heart rate variability. Diabetes is another area, where angiotensin II withdrawal has proven to be of particular value. We postulated that aldosterone blockade with spironolactone might also have beneficial effects on the prognostic markers of endothelial function and heart rate variability in diabetic patients.', 'We assessed endothelial function by forearm venous occlusion plethysmography in 42 patients with type 2 diabetes mellitus after 1 month of treatment with spironolactone or placebo allocated in a randomised double-blind trial. Of the 42 patients, 20 were on ACE inhibitor therapy. We also assessed heart rate variability, HbA1c and plasma angiotensin II levels at the end of each treatment period.', 'Compared to placebo, spironolactone decreased forearm blood flow response to acetylcholine by 44.56+/-14.56% (p=0.003) in the group as a whole and by 57.61+/-15.56% (p<0.001) in the 20 patients on ACE inhibition. Spironolactone also worsened heart rate variability parameters, with root mean squared standard deviation decreased by 1.99+/-0.93 ms (p=0.03), low-frequency normalised power increased by 2.00+/-0.91 normalised units (nu) (p=0.03), high-frequency normalised power decreased by 1.98+/-0.94 nu (p=0.04) and the low frequency : high frequency ratio increased by 0.40+/-0.19 (p=0.04). HbA1c and angiotensin II increased during treatment with spironolactone by 0.26+/-0.07% (p=0.001) and 8.12+/-1.94 pg/ml (p=0.001) respectively.",
            "output": [
                "Does spironolactone impair endothelial function and heart rate variability in patients with type 2 diabetes?"
            ]
        },
        {
            "id": "task847-64d87e3b67864a5ca27fd416a0f26f0f",
            "input": "Because of the side effects of Teflon, the risk of infection from the use of collagen, autologous fat resorption, and the lack of alternative substances, injection laryngoplasty tends to be replaced by laryngeal framework surgery as the method of choice for the treatment of unilateral vocal cord recurrent paralysis (LP). The aim of this study was to evaluate the results, for morbidity and voice quality, of treating this paralysis by injection of a silicone suspension elastomer implant (SSEI).', 'The study was retrospective, and 19 patients were included. Average follow-up was 25 months (range: 8.3-43).', 'Each patient underwent clinical and videostroboscopic assessment, and had an electroglottographic recording. Subjective assessment was obtained by self-evaluation. Results were classified as good, fair, or poor, and were based on 2 objective and 3 subjective criteria. A search was made for biologic signs of autoimmune disorders.', 'Good, fair, and poor results were respectively 79%, 16%, and 5%. Each set of subjective data showed voice improvement (P < 0.05). The fundamental frequency range, percentage of irregularity, and aspiration decreased significantly (P < 0.05). There was only one case of postoperative dyspnea, which resolved after steroid injection. No biologic signs of autoimmune disorders were found.",
            "output": [
                "Do endoscopic rehabilitation of vocal cord paralysis with a silicone elastomer suspension implant?"
            ]
        },
        {
            "id": "task847-15f7b4b648be4e8ba757b0bfe84b1799",
            "input": "Droperidol is useful for postoperative sedation in infants and children after cardiac surgery because it provides sedation and akinesia with minimal respiratory depression. However, droperidol has been associated with QT prolongation and ventricular arrhythmias. We investigated, if neuroleptanalgesic doses of droperidol led to QT prolongation and cardiac arrhythmias in children undergoing cardiac surgery.', 'We retrospectively analysed electrocardiogram rhythm strips that were obtained before and in time increments after a 100 microg x kg(-1) intravenous bolus of droperidol in 20 children undergoing cardiac surgery. The longest QT interval was determined in each ECG and corrected for heart rate (QTc). All arrhythmias were recorded.', 'Droperidol led to a significant increase in QTc time that was still present at 15 min but had resolved within 30 min after the bolus. No associated arrhythmias were observed.",
            "output": [
                "Does droperidol for perioperative sedation cause a transient prolongation of the QTc time in children under volatile anesthesia?"
            ]
        },
        {
            "id": "task847-8df06b1ec943411bac7ed00feee25b68",
            "input": "Is a perioperative metastatic screening programme indicated in patients presenting with primary operable breast cancer and no signs of distant metastases?', 'The impact of staging results (chest X-ray, bone scanning, liver ultrasound) for prognosis, treatment, quality of life and costs was retrospectively analysed in 1 076 patients with an operable breast cancer and no clinical signs of metastases.', 'Staging examinations revealed 30 (2.8 %) distant metastases, 130 (12.1 %) suspect findings and excluded metastases in 916 (85.1 %) patients. Further diagnostic procedures confirmed distant metastases in 7 (5.4 %) and excluded them in 123 (94.6 %) out of 130 patients with suspect findings. Distant metastases were detected more frequently with increasing tumor size (pT < or = 2.0 cm: 1.6 %, pT 2.1-5.0 cm: 3.0 %, respectively pT > 5.0 cm: 15.1 %; p < 0.001) and increasing number of involved axillary lymph nodes (pN0: 1.4 %, pN1-3 +: 1.8 %, pN4-9 +: 4.0 %, pN > 10 +: 12.5 %; p < 0.001). Due to false positive findings 123 (11.4 %) patients had to live for a significant period of time with the psychological distress of suspected metastatic disease. The abandonment of a perioperative screening in 1 076 patients saves costs of at least euro 259,366.68.",
            "output": [
                "Is [ A perioperative screening for metastatic disease indicated in patients with primary breast cancer and no clinical signs of tumor spread ]?"
            ]
        },
        {
            "id": "task847-fac332edf0fd4285bd6b08cbfbe7ae78",
            "input": "Knowledge concerning hormone replacement therapy (HRT) is rapidly changing.', 'We sought to understand the factors that influence how residents assimilate this knowledge.', 'We conducted an anonymous survey of residents in an internal medicine residency. Questions included personal demographic information and aspects of training (didactic and experiential) regarding and knowledge about HRT. Data were analyzed using univariable and multivariable linear regression.', \"Sixty-nine of 92 residents (75%) completed the survey. The gender and race of respondents did not differ significantly from the overall group. Knowledge scores were higher among residents in nontraditional (Women's Health, Primary Care, and Internal Medicine-Pediatrics) training tracks (p = .04) and among residents with patient population of < or = 30% postmenopausal women (p = .049). Demographic characteristics and didactic training about HRT did not influence knowledge.",
            "output": [
                "Does experiential learning influence residents knowledge about hormone replacement therapy?"
            ]
        },
        {
            "id": "task847-589979d2ea8b43c8822ac95c4c32e2e9",
            "input": "Evaluation of right ventricular (RV) function in patients with pulmonary regurgitation (PR) after tetralogy repair remains challenging because of abnormal RV loading conditions.', 'We examined 124 patients, aged 21+/-11.4 years, who had tetralogy repair at 3.7+/-3.5 years. By Doppler echocardiography, 33 patients had mild, 22 moderate, and 69 severe PR; 55 had significant tricuspid regurgitation (TR). Myocardial velocities, myocardial acceleration during isovolumic contraction (IVA), strain, and strain rate were measured at RV and LV base. Tricuspid valve annulus was measured in a 4-chamber view. QRS, QT, and JT intervals and their dispersions were measured from 12-lead electrocardiogram. IVA in the RV was lower in all patients compared with controls (0.8+/-0.4 versus 1.8+/-0.5, P<0.0001) and correlated with the severity of PR (r=-0.43, P<0.0001), whereas myocardial velocities, and strain/strain rate did not. LV IVA correlated with PR (r=-0.32, P<0.001) and with RV IVA (r=0.28, P<0.003). Patients with severe PR had a higher incidence of TR (r=0.69, P<0.0001) and lower RV IVA (1.0+/-0.4 versus 0.6+/-0.3, P<0.0001), a larger tricuspid valve ring diameter (P<0.0001), and prolonged electrical depolarization (P<0.001). Age at surgery or examination did not correlate with PR and with RV function assessed by IVA. In the RV, IVA correlated inversely with QRS duration (P<0.01).",
            "output": [
                "Is pulmonary regurgitation an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot?"
            ]
        },
        {
            "id": "task847-f57f35e2e3284821933340e2e2f908a8",
            "input": "Left ventricular aneurysm repair (LVR) reduces LV wall stress and improves LV function. However, as we reported previously, the initial improvement of LVR was short-term because of LV remodeling but could be maintained longer with postoperative use of an angiotensin-converting enzyme (ACE) inhibitor. Atrial natriuretic peptide (ANP) has been used to treat patients with heart failure by natriuretic and vasodilatory actions. Recent reports have suggested that ANP inhibits the rennin-angiotensin system. In this study, the effects of ANP after LVR were evaluated.', 'Rats that had an LV aneurysm 4 weeks after left anterior descending artery ligation underwent LVR by plicating the LV aneurysm and were randomized into 2 groups: LVR+A group was intravenously administrated with 10 microg/h of carperitide, recombinant alpha-hANP, by osmotic-pump for 4 weeks, and the LVR group was given normal saline. Echocardiography revealed better LV remodeling and function in LVR+A group than in LVR group. Four weeks after LVR, left ventricular end diastolic pressure (LVEDP) and Tau were significantly lower in LVR+A group (LVEDP: 10+/-4 in LVR+A group versus 18+/-6 mm Hg in LVR group, Tau: 13+/-2 versus 17+/-2ms). End-systolic elastance (Ees) was higher in LVR+A group (Ees: 0.34+/-0.2 versus 0.19+/-0.11 mm Hg/microL). The levels of myocardial ACE activity in LVR+A group was significantly lower than in LVR group. The mRNA expressions of brain natriuretic peptide and transforming growth factor beta1 inducing fibrosis significantly decreased in LV myocardium in LVR+A group. Histologically, myocardial fibrosis was significantly reduced in LVR+A group.",
            "output": [
                "Does atrial natriuretic peptide help prevent late remodeling after left ventricular aneurysm repair?"
            ]
        },
        {
            "id": "task847-905f3dd26eca45bbadcc7f293580098a",
            "input": "To evaluate the efficacy of a novel lipopolysaccharide (LPS) antagonist, E5531, in blocking LPS-induced cardiac responses including myocardial depression (as assessed by relatively load-independent echocardiographic indices of contractility) in a human model of experimental endotoxemia.', 'Randomized, prospective, placebo-controlled, double-blind trial.', 'ICU procedure room.', 'Thirty-two healthy, male volunteers.', 'Administration of LPS (4 ng/kg) and either a placebo or one of four sequential doses of E5531 (100 microg, 250 microg, 500 microg, or 1,000 microg) followed by volumetric echocardiography before and during 4-L saline solution infusion (3 L over 3 h, followed by 1 L over 2 h).', 'In addition to the generation of a hyperdynamic circulation throughout the study period, administration of LPS resulted in a biphasic contractility response. Ejection fraction (EF), rate-corrected mean velocity of circumferential fiber shortening (Vcfc), peak systolic BP (SBP)/end-systolic volume index (ESVI) ratio, and end-systolic pressure (Pes)/ESVI ratio increased at the 3-h post-LPS assessment, compared to a control group of subjects receiving only similar amounts of saline solution (minimum p < 0.001). End-systolic myocardial wall stress (sigmaes)/ESVI ratio, one of the most load independent of the contractility indices, was unchanged. At 5 h after endotoxin, EF, Vcfc, SBP/ESVI, Pes/ESVI, and sigmaes/ESVI were all decreased (minimum p < 0.01), indicating myocardial depression. When present, early (3 h after LPS), apparent enhancement of myocardial contractility and later (5 h after LPS) myocardial depression were substantially blunted by administration of E5531 (minimum p < 0.025), typically in a concentration-dependent manner.",
            "output": [
                "Is experimental human endotoxemia associated with depression of load-independent contractility indices : prevention by the lipid a analogue E5531?"
            ]
        },
        {
            "id": "task847-b7904b4646c44985b46cc9a9dafe35b3",
            "input": "Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory.', 'Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events].', 'High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues. High survivin concentrations were most strongly associated with estrogen receptor- or progesterone receptor-negative tumors. In univariate Cox regression analysis for RFS, survivin concentrations were significantly associated with poor prognosis with a hazard ratio (HR) of 1.99 (95% confidence interval, 1.31-3.02; P = 0.001) for every 10-fold increase in expression. For OS, a significant contribution of survivin to poor prognosis was found with a HR of 2.76 (1.67-4.55; P <0.001). Multivariate analyses were performed including established clinicopathologic factors. For RFS, age (P = 0.027), nodal category (P <0.001), and survivin [HR = 1.78 (1.18-2.68); P = 0.006] contributed significantly to the model. For OS, only nodal category (P <0.001) and survivin [HR = 3.05 (1.83-5.10); P <0.001] were significant.",
            "output": [
                "Is survivin an independent prognostic marker for risk stratification of breast cancer patients?"
            ]
        },
        {
            "id": "task847-0fb7a9dba26a446f8ceebc53a5987a74",
            "input": "Research on olfactory G-protein coupled receptors (GPCRs) has been severely impeded by poor functional expression in heterologous systems. Previously, we demonstrated that inefficient olfactory receptor (OR) expression at the plasma membrane is attributable, in part, to degradation of endoplasmic reticulum (ER)-retained ORs by the ubiquitin-proteasome system and sequestration of ORs in ER aggregates that are degraded by autophagy. Thus, experiments were performed to test the hypothesis that attenuation of ER degradation improves OR functional expression in heterologous cells.', 'To develop means to increase the functional expression of ORs, we devised an approach to measure activation of the mOREG OR (Unigene # Mm.196680; Olfr73) through coupling to an olfactory cyclic nucleotide-gated cation channel (CNG). This system, which utilizes signal transduction machinery coupled to OR activation in native olfactory sensory neurons, was used to demonstrate that degradation, both by the ubiquitin-proteasome system and autophagy, limits mOREG functional expression. The stimulatory effects of proteasome and autophagy inhibitors on mOREG function required export from the ER and trafficking through the biosynthetic pathway.",
            "output": [
                "Does endoplasmic reticulum degradation impede olfactory G-protein coupled receptor functional expression?"
            ]
        },
        {
            "id": "task847-e2ea9b98dba941749dd1735740ffdd49",
            "input": "The inducible nitric oxide synthase (iNOS) is associated with inflammatory processes and cancer formation through production of nitric oxide (NO). However, the clinical importance of the expression of iNOS in oral cancer remains unclear. In the present study, we examined whether up-regulation of the iNOS gene can affect growth and metastasis of an oral cancer cell line (B88t cell) in vitro and in vivo.', 'We constructed an expression vector containing sense-oriented murine iNOS cDNA with pcDNA3.1. We transfected B88t cells with the sense expression vector to up-regulate the expression of the iNOS gene in the sense transfectants.', 'The expression of iNOS protein was up-regulated in the sense transfectants and that up-regulation of the iNOS gene exerted a growth inhibitory effect on B88t cells in vitro and in vivo. Moreover, up-regulation of the iNOS gene markedly inhibited the migration of cancer cells in a Boyden chamber. Furthermore, up-regulation of the iNOS gene dramatically inhibited metastases to the cervical lymph node in vivo.",
            "output": [
                "Does overexpression of iNOS gene suppress the tumorigenicity and metastasis of oral cancer cells?"
            ]
        },
        {
            "id": "task847-38237bd18ce74698825fc9f2dea502d8",
            "input": "The current study was performed to assess the value of 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in predicting the pathologic response and survival of patients with esophageal carcinoma treated with preoperative chemoradiation (CRT) and tumor resection. Preliminary reports suggest that FDG-PET may be predictive of the response of esophageal carcinoma patients to preoperative CRT.', 'Eighty-three patients with resectable esophageal carcinoma who underwent preoperative CRT and FDG-PET and tumor resection were evaluated for pathologic response to CRT, percent residual tumor, and survival.', 'The majority of patients in the current study were men (74 of 83 patients; 89%). Most tumors were adenocarcinomas (73 of 83 tumors; 88%) and clinical (EUS)T3/4 (69 tumors; 83%) or N1 (46 tumors; 55%). FDG-PET after preoperative CRT identified pathologic responders but failed to rule out microscopic residual tumor in 13 of 73 cases (18%). Pathologic response was found to correlate with the post-CRT FDG-PET standardized uptake value (SUV) (P = 0.03) and a post-CRT FDG-PET SUV of or 4 was found to be the only preoperative factor to correlate with decreased survival (2-year survival rate of 33% vs. 60%; P = 0.01). On univariate Cox regression analysis, only post-CRT FDG-PET was found to be correlated with post-CRT survival (P = 0.04).",
            "output": [
                "Is 2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma?"
            ]
        },
        {
            "id": "task847-b275941ebd3e4fdbadb5ee1ed3f8e5d0",
            "input": "To evaluate the influence of osteoporosis on fracture healing.', 'Eighty-four 4 months old female Sprague-Dawley rats were randomly divided into osteoporosis (OP) group and sham operation (SO) group, 42 in each. Rats in OP group were performed ovariectomy operation while those in SO group with sham operation. When osteoporosis formed 10 weeks after ovariectomy, midshaft tibia fracture model was established. Tibias were harvested 2 weeks (2 rats per group), 4 weeks (9 rats per group), 6 weeks (9 rats per group), 12 weeks (9 rats per group) and 18 weeks (7 rats per group) after fracture for bone mineral density (BMD), histomorphological and biomechanical evaluation.', 'Compared with the SO group: (1) Callus BMD was significantly lower about 12.8%, 18.0%, 17.0% in OP group 6, 12, 18 weeks after fracture, respectively (P < 0.05). (2) Callus failure load was significantly lower about 24.3%, 31.5%, 26.6%, 28.8% in OP group, and callus failure stress was also significantly lower about 23.9%, 33.6%, 19.1%, 24.9% in OP group 4, 6, 12, 18 weeks after fracture, respectively (P < 0.05). (3) In OP group, endochondral bone formation was delayed, more osteoclast cell could be seen around the trabecula, and the new bone trabecula arranged loosely and irregularly.",
            "output": [
                "Does [ Osteoporosis impair fracture healing of tibia in a rat osteoporotic model ]?"
            ]
        },
        {
            "id": "task847-f188d53c27014b7d90e638e1d1ddda5e",
            "input": "Powerful growth-inhibitory action has been shown for n-3 polyunsaturated fatty acids against colon cancer cells. We have previously described their ability to inhibit proliferation of colon epithelial cells in patients at high risk of colon cancer. In the work reported here we investigated the ability of docosahexaenoic acid (DHA) to potentiate the antineoplastic activity of 5-fluorouracil (5-FU) in p53-wildtype (LS-174 and Colo 320) and p53-mutant (HT-29 and Colo 205) human colon cancer cells.', 'When in combination with DHA, 5-FU was used at concentrations ranging from 0.1 to 1.0 microM, much lower than those currently found in plasma patients after infusion of this drug. Similarly, the DHA concentrations (< or =10 microM) used in combination with 5-FU were lower than those widely used in vitro and known to cause peroxidative effects in vivo.', 'Whereas the cells showed different sensitivity to the growth-inhibitory action of 5-FU, DHA reduced cell growth independently of p53 cellular status. DHA synergized with 5-FU in reducing colon cancer cell growth. The potentiating effect of DHA was attributable to the enhancement of the proapoptotic effect of 5-FU. DHA markedly increased the inhibitory effect of 5-FU on the expression of the antiapoptotic proteins BCL-2 and BCL-XL, and induced overexpression of c-MYC which has recently been shown to drive apoptosis and, when overexpressed, to sensitize cancer cells to the action of proapoptotic agents, including 5-FU.",
            "output": [
                "Does docosahexaenoic acid enhance the susceptibility of human colorectal cancer cells to 5-fluorouracil?"
            ]
        },
        {
            "id": "task847-74f7ab4ece7b42049baf73fc8d29b47f",
            "input": "Epidemiological studies have reported associations between reduced cardiovascular disease and diets rich in tomato and/or lycopene. Intervention studies have shown that lycopene-containing foods may reduce cholesterol levels and lipid peroxidation, factors implicated in the initiation of cardiovascular disease. The objective of this study was to determine whether consumption of lycopene rich foods conferred cardiovascular protection to middle-aged adults as indicated by plasma lipid concentrations and measures of ex vivo antioxidants.', \"Ten healthy men and women consumed a low lycopene diet with no added lycopene (control treatment) or supplemented with watermelon or tomato juice each containing 20 mg lycopene. Subjects consumed each treatment for three weeks in a crossover design. Plasma, collected weekly was analyzed for total cholesterol, high density lipoprotein cholesterol (HDL-C) and triglyceride concentrations and for the antioxidant biomarkers of malondialdehyde formation products (MDA), plasma glutathione peroxidase (GPX) and ferric reducing ability of plasma (FRAP). Data were analyzed using Proc Mixed Procedure and associations between antioxidant and lipid measures were identified by Pearson's product moment correlation analysis.\", 'Compared to the control diet, the lycopene-containing foods did not affect plasma lipid concentrations or antioxidant biomarkers. Women had higher total cholesterol, HDL-C and triglyceride concentrations than did the men. Total cholesterol was positively correlated to MDA and FRAP while HDL-C was positively correlated to MDA and GPX. GPX was negatively correlated to triglyceride concentration.",
            "output": [
                "Does lycopene from two food sources affect antioxidant or cholesterol status of middle-aged adults?"
            ]
        }
    ],
    "Instance License": [
        "MIT"
    ]
}